FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wolpin, SE Halpenny, B Whitman, G McReynolds, J Stewart, M Lober, WB Berry, DL AF Wolpin, S. E. Halpenny, B. Whitman, G. McReynolds, J. Stewart, M. Lober, W. B. Berry, D. L. TI Development and usability testing of a web-based cancer symptom and quality-of-life support intervention SO HEALTH INFORMATICS JOURNAL LA English DT Article DE consumer health information; decision-support systems; ehealth; evidence-based practice; IT design and development methodologies ID INFORMATION-SYSTEMS; ONCOLOGY PRACTICE; COMPUTER; QUESTIONNAIRES; ACCEPTABILITY AB The feasibility and acceptability of computerized screening and patient-reported outcome measures have been demonstrated in the literature. However, patient-centered management of health information entails two challenges: gathering and presenting data using "patient-tailored" methods and supporting "patient-control" of health information. The design and development of many symptom and quality-of-life information systems have not included opportunities for systematically collecting and analyzing user input. As part of a larger clinical trial, the Electronic Self-Report Assessment for Cancer-II project, participatory design approaches were used to build and test new features and interfaces for patient/caregiver users. The research questions centered on patient/caregiver preferences with regard to the following: (a) content, (b) user interface needs, (c) patient-oriented summary, and (d) patient-controlled sharing of information with family, caregivers, and clinicians. Mixed methods were used with an emphasis on qualitative approaches; focus groups and individual usability tests were the primary research methods. Focus group data were content analyzed, while individual usability sessions were assessed with both qualitative and quantitative methods. We identified 12 key patient/caregiver preferences through focus groups with 6 participants. We implemented seven of these preferences during the iterative design process. We deferred development for some of the preferences due to resource constraints. During individual usability testing (n = 8), we were able to identify 65 usability issues ranging from minor user confusion to critical errors that blocked task completion. The participatory development model that we used led to features and design revisions that were patient centered. We are currently evaluating new approaches for the application interface and for future research pathways. We encourage other researchers to adopt user-centered design approaches when building patient-centered technologies. C1 [Wolpin, S. E.; Whitman, G.; McReynolds, J.; Stewart, M.; Lober, W. B.; Berry, D. L.] Univ Washington, Seattle, WA 98195 USA. [Halpenny, B.; Berry, D. L.] Dana Farber Canc Inst, Boston, MA USA. RP Wolpin, SE (reprint author), Univ Washington, Sch Nursing, Biobehav Nursing & Hlth Syst, Box 357266, Seattle, WA 98195 USA. EM swolpin@uw.edu FU NIH [R01 NR 008726] FX This work was supported by NIH under grant R01 NR 008726. NR 40 TC 4 Z9 4 U1 3 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1460-4582 EI 1741-2811 J9 HEALTH INFORM J JI Health Inform. J. PD MAR PY 2015 VL 21 IS 1 BP 10 EP 23 DI 10.1177/1460458213495744 PG 14 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CD7OR UT WOS:000351280600002 PM 24406906 ER PT J AU Parsons, EC Hough, CL Vitiello, MV Zatzick, D Davydow, DS AF Parsons, Elizabeth C. Hough, Catherine L. Vitiello, Michael V. Zatzick, Douglas Davydow, Dimitry S. TI Insomnia is associated with quality of life impairment in medical-surgical intensive care unit survivors SO HEART & LUNG LA English DT Article DE Insomnia; Post-traumatic stress disorder; Depression; Critical care; Intensive care; Outcome assessment ID MAJOR DEPRESSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; CRITICALLY ILL PATIENTS; POSTTRAUMATIC-STRESS; SEVERITY INDEX; SLEEP; VALIDATION; SYMPTOMS; MULTICENTER; MORBIDITY AB Objectives: To examine the prevalence of insomnia and its relationship to health-related quality of life (HRQOL) post-intensive care unit (ICU). Background: The burden of post-ICU insomnia is unknown. Methods: This cross-sectional study examined data from 120 patients with an ICU stay >24 h. Prehospital health was assessed in-hospital. Insomnia, HRQOL and post-ICU psychiatric symptoms were assessed at 12 months post-ICU. Results: Over one-quarter (28%) of subjects met insomnia criteria at 12 months post-ICU. Post-ICU insomnia was independently associated with worse mental HRQOL (P < 0.01), as well as worse scores on the HRQOL sub-domains of bodily pain (P < 0.001), vitality (P < 0.05) and physical function (P < 0.05). However, these associations were no longer significant after adjusting for post-ICU psychiatric symptoms (P = 033). Conclusions: Insomnia is common among ICU survivors. Post-ICU insomnia is significantly associated with mental HRQOL and could identify ICU survivors who may benefit from further psychiatric evaluation. Published by Elsevier Inc. C1 [Parsons, Elizabeth C.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Parsons, Elizabeth C.; Hough, Catherine L.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Vitiello, Michael V.; Zatzick, Douglas; Davydow, Dimitry S.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Parsons, EC (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM elizabeth.parsons@va.gov FU National Institutes of Health [KL2 TR000421, NRSA-T32/MH20021-12, R03 AA020146-02, K24 MH086814-03]; University of Washington Alcohol and Drug Abuse Institute [ADAI-1009-2] FX This work was performed at Harborview Medical Center, supported by grants KL2 TR000421, NRSA-T32/MH20021-12, R03 AA020146-02, and K24 MH086814-03 from the National Institutes of Health and grant ADAI-1009-2 from the University of Washington Alcohol and Drug Abuse Institute. The views expressed here are those of the authors and do not reflect the position or policy of the Department of Veterans Affairs. NR 39 TC 2 Z9 3 U1 3 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 EI 1527-3288 J9 HEART LUNG JI Heart Lung PD MAR-APR PY 2015 VL 44 IS 2 BP 89 EP 94 DI 10.1016/j.hrting.2014.11.002 PG 6 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA CD4BK UT WOS:000351027400003 PM 25592203 ER PT J AU DiPasquale, DM Kolkhorst, FW Buono, MJ AF DiPasquale, Dana M. Kolkhorst, Fred W. Buono, Michael J. TI Acute Normobaric Hypoxia Reduces Body Temperature in Humans SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE oxygen saturation; altitude; anapyrexia; thermoregulation; rectal ID ACUTE MOUNTAIN-SICKNESS; BROWN ADIPOSE-TISSUE; METABOLIC-RESPONSES; PHYSIOLOGICAL-RESPONSES; INDUCED HYPOTHERMIA; INDUCED ANAPYREXIA; CORE TEMPERATURE; BUFO-PARACNEMIS; CARDIAC-ARREST; COLD-EXPOSURE AB DiPasquale, Dana M., Fred W. Kolkhorst, and Michael J. Buono. Acute normobaric hypoxia reduces body temperature in humans. High Alt Med Biol 16:61-66, 2015.- Anapyrexia is the regulated decrease in body temperature during acute exposure to hypoxia. This study examined resting rectal temperature (T-rec) in adult humans during acute normobaric hypoxia (NH). Ten subjects breathed air consisting of 21% (NN), 14% (NH14), and 12% oxygen (NH12) for 30 min each in thermoneutral conditions while T-rec and blood oxygen saturation (Spo(2)) were measured. Linear regression indicated that Spo(2) was progressively lower in NH14 (p=0.0001) and NH12 (p=0.0001) compared to NN, and that Spo(2) in NH14 was different than NH12 (p=0.00001). T-rec was progressively lower during NH14 (p=0.014) and in NH12 (p=0.0001) compared to NN. The difference in T-rec between NH14 and NH12 was also significant (p=0.0287). Spo(2) was a significant predictor of T-rec such that for every 1% decrease in Spo(2), T-rec decreased by 0.15 degrees C (p=0.0001). The present study confirmed that, similar to many other species, human adults respond to acute hypoxia exposure by lowering rectal temperature. C1 [DiPasquale, Dana M.] Univ Pittsburgh, Dept Sports Med & Nutr, Pittsburgh, PA 15203 USA. [DiPasquale, Dana M.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Kolkhorst, Fred W.; Buono, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. [Buono, Michael J.] San Diego State Univ, Dept Exercise & Nutr Sci, San Diego, CA 92182 USA. San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. RP DiPasquale, DM (reprint author), Univ Pittsburgh, Dept Sports Med & Nutr, 3830 South Water St, Pittsburgh, PA 15203 USA. EM dmd116@pitt.edu NR 68 TC 2 Z9 2 U1 6 U2 10 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 EI 1557-8682 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD MAR 1 PY 2015 VL 16 IS 1 BP 61 EP 66 DI 10.1089/ham.2014.1098 PG 6 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA CD9WV UT WOS:000351451900010 PM 25803142 ER PT J AU Ellis, CN LaRocque, RC Uddin, T Krastins, B Mayo-Smith, LM Sarracino, D Karlsson, EK Rahman, A Shirin, T Bhuiyan, TR Chowdhury, F Khan, AI Ryan, ET Calderwood, SB Qadri, F Harris, JB AF Ellis, Crystal N. LaRocque, Regina C. Uddin, Taher Krastins, Bryan Mayo-Smith, Leslie M. Sarracino, David Karlsson, Elinor K. Rahman, Atiqur Shirin, Tahmina Bhuiyan, Taufiqur R. Chowdhury, Fahima Khan, Ashraful Islam Ryan, Edward T. Calderwood, Stephen B. Qadri, Firdausi Harris, Jason B. TI Comparative Proteomic Analysis Reveals Activation of Mucosal Innate Immune Signaling Pathways during Cholera SO INFECTION AND IMMUNITY LA English DT Article ID NF-KAPPA-B; T-CELL RESPONSES; NLRP3 INFLAMMASOME ACTIVATION; TRANSFER-RNA-SYNTHETASE; LIPOCALIN 2 EXPRESSION; NITRIC-OXIDE SYNTHASE; VIBRIO-CHOLERAE; DENDRITIC CELLS; PROTEIN-KINASE; TH17 CELLS AB Vibrio cholerae O1 is a major cause of acute watery diarrhea in over 50 countries. Evidence suggests that V. cholerae O1 may activate inflammatory pathways, and a recent study of a Bangladeshi population showed that variants in innate immune genes play a role in mediating susceptibility to cholera. We analyzed human proteins present in the small intestine of patients infected with V. cholerae O1 to characterize the host response to this pathogen. We collected duodenal biopsy specimens from patients with acute cholera after stabilization and again 30 days after initial presentation. Peptides extracted from biopsy specimens were sequenced and quantified using label-free mass spectrometry and SEQUEST. Twenty-seven host proteins were differentially abundant between the acute and convalescent stages of infection; the majority of these have known roles in innate defense, cytokine production, and apoptosis. Immunostaining confirmed that two proteins, WARS and S100A8, were more abundant in lamina propria cells during the acute stage of cholera. Analysis of the differentially abundant proteins revealed the activation of key regulators of inflammation by the innate immune system, including Toll-like receptor 4, nuclear factor kappa-light-chain-enhancer of activated B cells, mitogen-activated protein kinases, and caspase-dependent inflammasomes. Interleukin-12 beta(IL-12 beta) was a regulator of several proteins that were activated during cholera, and we confirmed that IL-12 beta was produced by lymphocytes recovered from duodenal biopsy specimens of cholera patients. Our study shows that a broad inflammatory response is generated in the gut early after onset of cholera, which may be critical in the development of long-term mucosal immunity against V. cholerae O1. C1 [Ellis, Crystal N.; LaRocque, Regina C.; Mayo-Smith, Leslie M.; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Uddin, Taher; Rahman, Atiqur; Shirin, Tahmina; Bhuiyan, Taufiqur R.; Chowdhury, Fahima; Khan, Ashraful Islam; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Krastins, Bryan; Sarracino, David] Biomarker Res Mass Spectrometry, ThermoFischer Sci, Cambridge, MA USA. [Ellis, Crystal N.; LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Karlsson, Elinor K.] Harvard Univ, Dept Organism & Evolutionary Biol, Ctr Syst Biol, Cambridge, MA 02138 USA. [Karlsson, Elinor K.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Ellis, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM cnellis@mgh.harvard.edu; jbharris@mgh.harvard.edu OI Karlsson, Elinor/0000-0002-4343-3776 FU International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (icddr, b); National Institutes of Health, including the National Institute of Allergy and Infectious Diseases [AI058935, AI106878, R01 AI099243, R01 AI103055]; Vaccine Development and Public Health [TW005572] FX This work was supported by grants from the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (icddr, b), and the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI058935 and AI106878 to E.T.R.; R01 AI099243 and R01 AI103055 to J.B.H.) and a training grant in Vaccine Development and Public Health (TW005572 to T.U. and T.R.B.). NR 77 TC 6 Z9 6 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2015 VL 83 IS 3 BP 1089 EP 1103 DI 10.1128/IAI.02765-14 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CD6WG UT WOS:000351230200024 PM 25561705 ER PT J AU Bottche, M Pietrzak, RH Kuwert, P Knaevelsrud, C AF Boettche, Maria Pietrzak, Robert H. Kuwert, Philipp Knaevelsrud, Christine TI Typologies of posttraumatic stress disorder in treatment-seeking older adults SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE latent profile analysis; typology; older adults; early-life traumatization; PTSD ID CONFIRMATORY FACTOR-ANALYSIS; COMORBIDITY SURVEY REPLICATION; LATENT CLASS ANALYSIS; HOLOCAUST SURVIVORS; PTSD CHECKLIST; SYMPTOMS; VETERANS; NUMBER; SCALE AB Background: While it is well known that posttraumatic stress disorder (PTSD) is characterized by heterogeneous symptom clusters, little is known about predominant typologies of PTSD symptoms in older adults. Methods: Latent profile analyses (LPAs) were employed to evaluate predominant typologies of PTSD symptoms in a sample of 164 treatment-seeking older adults with childhood war-related trauma. Multinomial logistic regressions were conducted to evaluate predictors of class membership. Results: LPAs revealed that a 3-class solution best fit the data. These included an Intermediate Disturbance class (50.0%) and two Pervasive Disturbance classes, which differed with respect to severity of avoidance symptoms (Pervasive Disturbance-Low Avoidance: 33.5%, Pervasive Disturbance-High Avoidance: 16.5%). A greater number of traumatic events predicted membership in the Pervasive Disturbance classes. The Pervasive Disturbance-Low Avoidance class had a higher level of education than the Pervasive Disturbance-High Avoidance class. Compared to the Intermediate Disturbance class, the Pervasive Disturbance classes had the highest levels of depression, anxiety and somatization symptoms. Conclusion: These results suggest that PTSD in treatment-seeking older adults may be characterized by three predominant typologies, which are differentiated by overall severity and avoidance symptoms, lifetime trauma burden, education level, and comorbid depression, anxiety, and somatization symptoms. These results underscore the importance of considering heterogeneity in the phenotypic presentation of PTSD in assessment and treatment approaches for this disorder in older adults. C1 [Boettche, Maria; Knaevelsrud, Christine] Berlin Ctr Torture Victims, Berlin, Germany. [Boettche, Maria; Knaevelsrud, Christine] Free Univ Berlin, Dept Clin Psychol & Psychotherapy, Berlin, Germany. [Pietrzak, Robert H.] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Kuwert, Philipp] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, HELIOS Hansehosp Stralsund, Greifswald, Germany. RP Bottche, M (reprint author), Treatment Ctr Torture Victims, Turmstr 21, D-10559 Berlin, Germany. EM m.boettche@bzfo.de NR 31 TC 2 Z9 2 U1 0 U2 4 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 MAR PY 2015 VL 27 IS 3 BP 501 EP 509 DI 10.1017/S1041610214002026 PG 9 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA CD4MM UT WOS:000351057100016 PM 25234418 ER PT J AU Rumsfeld, JS Holmes, DR Stough, WG Edwards, FH Jacques, LB Mack, MJ AF Rumsfeld, John S. Holmes, David R. Stough, Wendy Gattis Edwards, Fred H. Jacques, Louis B. Mack, Michael J. TI Insights From the Early Experience of the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE Centers for Medicare and Medicaid Services (US); heart valve prosthesis implantation; investigational device exemption; National Cardiovascular Data Registry; registries; transcatheter aortic valve replacement; US Food and Drug Administration ID INFRASTRUCTURE; SURVEILLANCE AB The current system for postmarket surveillance of medical devices in the United States is limited. To help change this paradigm for transcatheter valve therapies (TVTs), starting with transcatheter aortic valve replacement, the Society of Thoracic Surgeons and the American College of Cardiology partnered to form the TVT Registry program in close collaboration with the U.S. Food and Drug Administration and the Center for Medicare and Medicaid Services. The goal of the TVT Registry is to measure and improve quality of care and patient outcomes in clinical practice and to have a pivotal role in the scientific evidence and surveillance for medical devices. Challenges were faced in the early experience of the registry included developing multistakeholder partnerships, data collection requirements, and the use of the registry for pre- and post-market device evaluations. In addressing these challenges, the TVT Registry demonstrates that it is feasible for professional societies to assume a pivotal role in pre- and/or post-market studies, leveraging a clinical registry infrastructure. Sharing the TVT Registry experience may help other professional societies and stakeholders better anticipate and plan for these challenges. (C) 2015 by the American College of Cardiology Foundation. C1 [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO 80220 USA. [Holmes, David R.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Stough, Wendy Gattis] Campbell Univ, Coll Pharm & Hlth Sci, Buies Creek, NC 27506 USA. [Edwards, Fred H.] Univ Florida, Hlth Sci Ctr, Jacksonville, FL 32209 USA. [Jacques, Louis B.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Mack, Michael J.] Heart Hosp Baylor, Baylor Healthcare Syst, Dallas, TX USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, Cardiol 111B, 1055 Clermont St, Denver, CO 80220 USA. EM john.rumsfeld@va.gov RI Stough, Wendy/R-4287-2016 OI Stough, Wendy/0000-0001-8290-1205 NR 7 TC 8 Z9 8 U1 1 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 MAR PY 2015 VL 8 IS 3 BP 377 EP 381 DI 10.1016/j.jcin.2014.09.022 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CD6TC UT WOS:000351221300007 PM 25703888 ER PT J AU Lindsay, RW Bhama, P Hohman, M Hadlock, TA AF Lindsay, Robin W. Bhama, Prabhat Hohman, Marc Hadlock, Tessa A. TI Prospective Evaluation of Quality-of-Life Improvement After Correction of the Alar Base in the Flaccidly Paralyzed Face SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID NASAL VALVE COLLAPSE; FUNCTIONAL RHINOPLASTY; SECONDARY RHINOPLASTY; CLINICAL-APPLICATIONS; AIR-FLOW; OUTCOMES; GRAFT; REHABILITATION; COMPLICATIONS; MANAGEMENT AB IMPORTANCE Nasal valve collapse caused by facial palsy is an often overlooked but disturbing sequela of flaccid facial paralysis. OBJECTIVE To prospectively study the effect of fascia lata sling placement for correction of external nasal valve compromise in patients with flaccid facial paralysis, using a validated disease-specific quality-of-life outcome survey. DESIGN, SETTING, AND PARTICIPANTS This was a prospective study of 68 patients from March 2009 to December 2013 who underwent fascia lata sling placement for correction of external nasal valve compromise. INTERVENTION Fascia lata sling placement for the correction of external nasal valve compromise. MAIN OUTCOME AND MEASURE Nasal Obstruction Symptom Evaluation (NOSE) scale. RESULTS Sixty-eight disease-specific quality-of-life determinations were performed using the NOSE scale. Ratings were ascertained preoperatively and postoperatively. Sixty patients completed a NOSE scale prior to surgical intervention, and 40 completed the survey after intervention. There was a statistically significant difference in NOSE scores after fascia lata sling placement The mean preoperative NOSE score was 37.6 (27.1), and the mean postoperative score was 16.6 (17.37) (Wilcoxon signed-rank test; P < .001). All patients had improvement in their nasal obstruction, which persisted uniformly in follow-up. CONCLUSIONS AND RELEVANCE The nasal valve is a zone that has historically been neglected, despite the fact that a highly effective surgical solution has existed for decades. We highlight the significance of nasal valve dysfunction in patients with flaccid facial paralysis, demonstrate a quantitative benefit in disease-specific quality of life after fascia late sling placement for external nasal valve compromise, and suggest an updated treatment algorithm. This method offers a predictably successful, straightforward surgical solution to an overlooked functional problem in the patient with flaccid facial paralysis. C1 [Lindsay, Robin W.; Bhama, Prabhat; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Lindsay, Robin W.; Bhama, Prabhat; Hadlock, Tessa A.] Harvard Univ, Sch Med, Boston, MA USA. [Hohman, Marc] Madigan Army Med Ctr, Dept Otolaryngol Head & Neck Surg, Tacoma, WA 98431 USA. RP Lindsay, RW (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM robin_lindsay@meei.harvard.edu FU Leslie Bernstein grant; American Academy of Facial Plastic and Reconstructive Surgery FX This study received funding from the Leslie Bernstein grant, a CORE grant funded by the American Academy of Facial Plastic and Reconstructive Surgery. NR 26 TC 6 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD MAR-APR PY 2015 VL 17 IS 2 BP 108 EP 112 DI 10.1001/jamafacial.2014.1295 PG 5 WC Surgery SC Surgery GA CE0JL UT WOS:000351490200008 PM 25554967 ER PT J AU Shaye, DA Tollefson, TT Strong, EB AF Shaye, David A. Tollefson, Travis T. Strong, E. Bradley TI Use of Intraoperative Computed Tomography for Maxillofacial Reconstructive Surgery SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID FRACTURES; CT; MANAGEMENT AB IMPORTANCE Intraoperative computed tomography (CT) provides surgeons with real-time feedback during maxillofacial trauma and reconstructive surgery, which can affect intraoperative decision making. OBJECTIVES To evaluate the time needed to perform intraoperative CT scans during maxillofacial surgery, determine any trend toward shorter total scan times as experience is gained with the technique, and identify the characteristics of cases that required intraoperative revision based on the results of intraoperative CT scanning. DESIGN, SETTING, AND PARTICIPANTS A retrospective review was completed for all maxillofacial reconstruction procedures that used intraoperative CT between January 1, 2012, and March 31, 2014. INTERVENTIONS Patients were cared for by the routine practice pattern of the authors. Intraoperative CT scans were obtained for all patients. MAIN OUTCOMES AND MEASURES Time needed for intraoperative CT scan was measured and trends were analyzed. Covariates included age, sex, complexity of fracture, procedure type, total scan time, surgeon, and need for intraoperative revision based on intraoperative CT findings. RESULTS Thirty-eight cases were identified, including 30 males (79%) and 8 females (21%). The mean (SE) age was 37.4 (16.0) years (range, 7-75 years). Cases were defined as routine (18 [47%]) or complex (20 [53%]). Isolated orbital fractures were the most common fracture (23 [61%]) in both the routine (14 [78%]) and complex (9 [45%]) cases. The mean (SE) total scan time was 14.5 (4.9) minutes (range, 6-27 minutes) and did not differ based on complexity (P = .34). Intraoperative revisions were performed in 9 patients (24%) and were more common in complex (n = 8) than routine (n = 1) cases (P = .004). There was no reduction in total scan time during the study period (P = .22). The mean (SE) scan time for the most experienced surgeon was 3.78 (1.53) minutes shorter than for the other surgeons as a group (P = .02). CONCLUSIONS AND RELEVANCE Current intraoperative CT scanning techniques are rapid, averaging 14.5 minutes per case. No decrease in total scan time was noted during the study; however, the surgeon most experienced with the CT software had the shortest total scan times. Intraoperative revisions were most common in complex cases. We recommend surgeons consider the use of intraoperative CT imaging for maxillofacial reconstruction, particularly in complex procedures. C1 [Shaye, David A.] Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. [Shaye, David A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02116 USA. [Tollefson, Travis T.; Strong, E. Bradley] Univ Calif Davis, Dept Otolaryngol Head & Neck Surg, Sacramento, CA 95817 USA. RP Shaye, DA (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Div Facial Plast & Reconstruct Surg,Massachusetts, 243 Charles St,Ninth Floor, Boston, MA 02116 USA. OI Tollefson, Travis/0000-0002-8658-8647 NR 12 TC 6 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD MAR-APR PY 2015 VL 17 IS 2 BP 113 EP 119 DI 10.1001/jamafacial.2014.1343 PG 7 WC Surgery SC Surgery GA CE0JL UT WOS:000351490200009 PM 25569785 ER PT J AU Scott, WJ Schrage, N Dohlman, C AF Scott, Wendell J. Schrage, Norbert Dohlman, Claes TI Emergency Eye Rinse for Chemical Injuries New Considerations SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID BURNS C1 [Scott, Wendell J.] Mercy Clin Eye Specialists, Springfield, MO 65804 USA. [Schrage, Norbert] Kliniken Stadt Koln gGmbH, Cologne, Germany. [Dohlman, Claes] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Scott, WJ (reprint author), Mercy Clin Eye Specialists, 1229 E Seminole,Ste 420, Springfield, MO 65804 USA. EM wendell.scott@mercy.net NR 5 TC 1 Z9 2 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAR PY 2015 VL 133 IS 3 BP 245 EP 245 DI 10.1001/jamaophthalmol.2014.5045 PG 1 WC Ophthalmology SC Ophthalmology GA CD6UE UT WOS:000351224200002 PM 25474079 ER PT J AU Gonzalez-Angulo, AM Krop, I Akcakanat, A Chen, HQ Liu, SY Li, YS Culotta, KS Tarco, E Piha-Paul, S Moulder-Thompson, S Velez-Bravo, V Sahin, AA Doyle, LA Do, KA Winer, EP Mills, GB Kurzrock, R Meric-Bernstam, F AF Gonzalez-Angulo, Ana M. Krop, Ian Akcakanat, Argun Chen, Huiqin Liu, Shuying Li, Yisheng Culotta, Kirk S. Tarco, Emily Piha-Paul, Sarina Moulder-Thompson, Stacy Velez-Bravo, Vivianne Sahin, Aysegul A. Doyle, Laurence A. Do, Kim-Anh Winer, Eric P. Mills, Gordon B. Kurzrock, Razelle Meric-Bernstam, Funda TI SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID AKT INHIBITOR MK-2206; TRASTUZUMAB RESISTANCE; PIK3CA MUTATIONS; CLINICAL-TRIAL; II TRIAL; COMBINATION; PATHWAY; PTEN; DISCOVERY; THERAPY AB Background: There is preclinical synergism between taxanes and MK-2206. We aim to determine the maximum tolerated dose, safety, and activity of combining MK-2206 and paclitaxel in metastatic cancer. Methods: Patients received weekly doses of paclitaxel at 80 mg/m2 on day 1, followed by MK-2206 orally on day 2 escalated at 90 mg, 135 mg, and 200 mg. Treatment continued until progression, excessive toxicity, or patient request. Blood and tissue were collected for pharmacokinetic and pharmacodynamics markers. A cycle consisted of three weeks of therapy. Dose-limiting toxicity (DLT) was defined as unacceptable toxicity during the first cycle. All statistical tests were two-sided. Results: Twenty-two patients were treated, nine in dose escalation and 13 in dose expansion. Median age was 55 years. Median number of cycles was four. Dose escalation was completed with no DLT. CTCAE Grade 3 or higher adverse events were fatigue (n = 2), rash (n = 2), hyperglycemia (n = 1), and neutropenia (n = 7). Four patients in the expansion phase required MK-2206 dose reduction. Phase II recommended dose was established as paclitaxel 80 mg/m2 weekly on day 1, and MK-2206 135 mg weekly on day 2. Paclitaxel systemic exposure was similar in the presence or absence of MK-2206. Plasma MK-2206 concentrations were similar to data from previous phase I monotherapy. There was a statistically significant decrease in expression of pAKT S473 (P = .01) and pAKT T308 (P = .002) after therapy. PI3K/AKT/mTOR downregulation in tumor tissues and circulating markers did not correlate with tumor response or clinical benefit. There were five objective responses, and nine patients had stable disease. Conclusion: MK-2206 was well tolerated with paclitaxel. Preliminary antitumor activity was documented. C1 [Gonzalez-Angulo, Ana M.; Liu, Shuying; Moulder-Thompson, Stacy] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Gonzalez-Angulo, Ana M.; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Chen, Huiqin; Li, Yisheng; Do, Kim-Anh] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Culotta, Kirk S.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Akcakanat, Argun; Tarco, Emily; Piha-Paul, Sarina; Velez-Bravo, Vivianne; Meric-Bernstam, Funda] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA. [Sahin, Aysegul A.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Meric-Bernstam, Funda] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Krop, Ian; Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Kurzrock, Razelle] Univ Calif San Diego, Div Hematol Oncol, San Diego, CA 92103 USA. [Doyle, Laurence A.] NCI, Canc Therapy Evaluat Program, NIH, Rockville, MD USA. RP Meric-Bernstam, F (reprint author), Univ Texas MD Anderson Canc Ctr, 1400 Holcombe Blvd,Unit 455, Houston, TX 77030 USA. EM fmeric@mdanderson.org OI LI, Yisheng/0000-0001-9847-8544 FU National Cancer Institute [1K23CA121994, U01 CA062461-18]; ASCO Career Development Award; Komen for the Cure Catalyst Award [KG090341]; American Cancer Society [121329-RSG-11-187-01-TBG, SUC2-AACR-DT0209 01]; Commonwealth Foundation for Cancer research FX This work was supported in part by National Cancer Institute 1K23CA121994 (AMG), ASCO Career Development Award (AMG), Komen for the Cure Catalyst Award KG090341 (AMG), American Cancer Society Research Scholar Grant 121329-RSG-11-187-01-TBG (AMG), SUC2-AACR-DT0209 01(AMG, GBM, FMB), National Cancer Institute U01 CA062461-18 (RK), and the Commonwealth Foundation for Cancer research (AMG). NR 27 TC 2 Z9 2 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD MAR PY 2015 VL 107 IS 3 AR dju493 DI 10.1093/jnci/dju493 PG 9 WC Oncology SC Oncology GA CD7TZ UT WOS:000351297400013 ER PT J AU Goodwin, PJ Parulekar, WR Gelmon, KA Shepherd, LE Ligibel, JA Hershman, DL Rastogi, P Mayer, IA Hobday, TJ Lemieux, J Thompson, AM Pritchard, KI Whelan, TJ Mukherjee, SD Chalchal, HI Oja, CD Tonkin, KS Bernstein, V Chen, BE Stambolic, V AF Goodwin, Pamela J. Parulekar, Wendy R. Gelmon, Karen A. Shepherd, Lois E. Ligibel, Jennifer A. Hershman, Dawn L. Rastogi, Priya Mayer, Ingrid A. Hobday, Timothy J. Lemieux, Julie Thompson, Alastair M. Pritchard, Kathleen I. Whelan, Timothy J. Mukherjee, Som D. Chalchal, Haji I. Oja, Conrad D. Tonkin, Katia S. Bernstein, Vanessa Chen, Bingshu E. Stambolic, Vuk TI Effect of Metformin vs Placebo on Weight and Metabolic Factors in NCIC CTG MA.32 SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID STAGE BREAST-CANCER; ACTIVATED PROTEIN-KINASE; INSULIN; OBESITY; TRIAL; WOMEN AB Background: Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hsCRP]) associated with poor breast cancer outcomes. The NCIC Clinical Trials Group (NCIC CTG) MA. 32 investigates effects of metformin vs placebo on invasive disease-free survival and other outcomes in early breast cancer. Maintaining blinding of investigators to outcomes, we conducted a planned, Data Safety Monitoring Committee-approved, analysis of the effect of metformin vs placebo on weight and metabolic factors at six months, including examination of interactions with baseline body mass index (BMI) and insulin, in the first 492 patients with paired blood samples. Methods: Eligible nondiabetic subjects with T1-3, N0-3, M0 breast cancer who had completed surgery and (neo) adjuvant chemotherapy (if given) provided fasting plasma samples at random assignment and at six months. Glucose was measured locally; blood was aliquoted, frozen, and stored at -80 degrees C. Paired plasma aliquots were analyzed for insulin, hs-CRP, and leptin. Spearman correlation coefficients were calculated and comparisons analyzed using Wilcoxon signed rank test. All statistical tests were two-sided. Results: Mean age was 52.1 +/- 9.5 years in the metformin group and 52.6 +/- 9.8 years in the placebo group. Arms were balanced for estrogen/progesterone receptor, BMI, prior (neo) adjuvant chemotherapy, and stage. At six months, decreases in weight and blood variables were statistically significantly greater in the metformin arm (vs placebo) in univariate analyses: weight -3.0%, glucose -3.8%, insulin -11.1%, homeostasis model assessment -17.1%, leptin -20.2%, hs-CRP -6.7%; all P values were less than or equal to .03. There was no statistically significant interaction of change in these variables with baseline BMI or insulin. Conclusions: Metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months. Effects did not vary by baseline BMI or fasting insulin. C1 [Goodwin, Pamela J.] Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Parulekar, Wendy R.; Shepherd, Lois E.; Chen, Bingshu E.] Queens Univ, Canc Res Inst, NCIC Clin Trials Grp, Kingston, ON, Canada. [Gelmon, Karen A.] Univ British Columbia, British Columbia Canc Agcy, NCIC Clin Trials Grp, Vancouver, BC V5Z 1M9, Canada. [Ligibel, Jennifer A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hershman, Dawn L.] Columbia Univ, Med Ctr, New York, NY USA. [Rastogi, Priya] Univ Pittsburgh, Inst Canc, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Mayer, Ingrid A.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Med Ctr, Nashville, TN USA. [Hobday, Timothy J.] Mayo Clin, Coll Med, Rochester, MN USA. [Lemieux, Julie] Hop St Sacrement, CHU Quebec, Ctr Rech, Unite Rech Sante Populat, Quebec City, PQ, Canada. [Thompson, Alastair M.] Natl Inst Canc Res, Breast Clin Studies Grp, London, England. [Pritchard, Kathleen I.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Whelan, Timothy J.; Mukherjee, Som D.] McMaster Univ, Juravinski Canc Ctr, Hamilton Hlth Sci, Hamilton, ON, Canada. [Chalchal, Haji I.] Allan Blair Canc Ctr, Regina, SK, Canada. [Oja, Conrad D.] British Columbia Canc Agcy, Fraser Valley Ctr, Surrey, BC, Canada. [Tonkin, Katia S.] Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. [Bernstein, Vanessa] Univ British Columbia, British Columbia Canc Agcy, Vancouver Isl Ctr, Vancouver, BC V5Z 1M9, Canada. [Stambolic, Vuk] Univ Toronto, Ontario Canc Inst, Univ Hlth Network, Princess Margaret Hosp, Toronto, ON M5S 1A1, Canada. RP Goodwin, PJ (reprint author), Mt Sinai Hosp, 1284-600 Univ Ave, Toronto, ON M5G 1X4, Canada. EM pgoodwin@mtsinai.on.ca RI Goodwin, Pamela/K-1477-2013; Whelan, Timothy/D-3185-2017 FU Canadian Cancer Society Research Institute [021039]; National Cancer Institute (US) [CA077202]; Breast Cancer Research Foundation (New York); Canadian Breast Cancer Foundation - Ontario Region (Ontario Institute for Cancer Research) [10NOV-467] FX This work was supported by the Canadian Cancer Society Research Institute (#021039), the National Cancer Institute (US) (#CA077202), the Breast Cancer Research Foundation (New York), Canadian Breast Cancer Foundation - Ontario Region (Ontario Institute for Cancer Research) (#10NOV-467), and Apotex Canada (in kind donation of placebo and metformin). NR 20 TC 12 Z9 12 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD MAR PY 2015 VL 107 IS 3 AR djv006 DI 10.1093/jnci/djv006 PG 8 WC Oncology SC Oncology GA CD7TZ UT WOS:000351297400017 ER PT J AU Mohanty, S Kinnier, CV Bilimoria, KY AF Mohanty, Sanjay Kinnier, Christine V. Bilimoria, Karl Y. TI Patient Satisfaction, Outcomes, and the Need for Cancer-Specific Quality Metrics SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CARE C1 [Mohanty, Sanjay; Kinnier, Christine V.; Bilimoria, Karl Y.] Surg Outcomes & Qual Improvement Ctr, Dept Surg, Chicago, IL USA. [Mohanty, Sanjay; Kinnier, Christine V.; Bilimoria, Karl Y.] Northwest Inst Comparat Effectiveness Res Oncol, Chicago, IL USA. [Mohanty, Sanjay] Henry Ford Hosp, Dept Surg, Detroit, MI 48202 USA. [Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Bilimoria, KY (reprint author), Northwestern Univ, Surg Outcomes & Qual Improvement Ctr, Dept Surg, Feinberg Sch Med, 633 N St Clair St,Suite 6-650, Chicago, IL 60611 USA. EM kbilimoria@nmff.org NR 7 TC 3 Z9 3 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD MAR PY 2015 VL 107 IS 3 AR dju438 DI 10.1093/jnci/dju438 PG 2 WC Oncology SC Oncology GA CD7TZ UT WOS:000351297400009 ER PT J AU Korde, LA Partridge, AH Esser, M Lewis, S Simha, J Johnson, RH AF Korde, Larissa A. Partridge, Ann H. Esser, Michelle Lewis, Stacy Simha, Joy Johnson, Rebecca H. TI Breast Cancer in Young Women: Research Priorities. A Report of the Young Survival Coalition Research Think Tank Meeting SO JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY LA English DT Article DE breast cancer; chemotherapy; fertility; metastasis; quality of life; survivorship ID QUALITY-OF-LIFE; BISPHENOL-A; MAMMOGRAPHIC DENSITY; CHILDHOOD-CANCER; RECEPTOR STATUS; TUMOR SUBTYPES; RISK; PREGNANCY; DIAGNOSIS; AGE AB Breast cancer in young women is a significant issue-7% of all female breast cancer is diagnosed in women under 40 years of age. Young women with breast cancer (YWBC) face significant and unique challenges, including a higher likelihood of biologically aggressive disease and metastatic disease at diagnosis, leading to poorer prognosis, more aggressive treatment and long-term treatment-related toxicities, and unique psychosocial concerns. This article summarizes the Young Survival Coalition (YSC) Research Think Tank Meeting, held in Arlington, Virginia, in February 2013, and presents the process that led to YSC's priorities for YWBC research. The meeting's participants focused on six broad categories of investigation in which additional advancements in research on YWBC are crucial: risk factors; treatment; fertility; pregnancy-associated breast cancer; quality of life and survivorship; and metastasis. Several key themes emerged from this meeting. Researchers and advocates felt that a large-scale data registry focused on YWBC is necessary to collect quality information to guide future research for YWBC. This database should include clinical data, genomic profiling of primary tumor and metastatic sites, and an increased focus on fertility and pregnancy following breast cancer treatment. The participants also felt that more must be done to elucidate how and why YWBC develop more aggressive tumors, and to what degree treatment should be modified for young women. The discussions summarized here led to the formulation of YSC's Research Agenda, published in May 2014. C1 [Korde, Larissa A.] Univ Washington, Div Med Oncol, Seattle, WA 98109 USA. [Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Esser, Michelle; Lewis, Stacy; Simha, Joy] Young Survival Coalit, New York, NY USA. [Johnson, Rebecca H.] Mary Bridge Childrens Hosp, Multicare Hlth Syst, Tacoma, WA USA. RP Korde, LA (reprint author), Univ Washington, Div Med Oncol, 825 Eastlake Ave E,G3-630, Seattle, WA 98109 USA. EM lkorde@u.washington.edu FU Avon Foundation for Women; Susan G. Komen for the Cure; Keep a Breast Foundation FX The authors would like to acknowledge all the participants of the working groups and Research Think Tank Meeting, as listed in Table 1. In addition to the Young Survival Coalition itself, funding for the Research Think Tank process and meeting was also provided by the Avon Foundation for Women, Susan G. Komen for the Cure, and the Keep a Breast Foundation. We would also like to thank Leapfrog Consulting for their assistance with facilitating the Research Think Tank Meeting. NR 87 TC 1 Z9 1 U1 2 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2156-5333 EI 2156-535X J9 J ADOLESC YOUNG ADUL JI J. Adolesc. Young Adult Oncol. PD MAR PY 2015 VL 4 IS 1 BP 34 EP 43 DI 10.1089/jayao.2014.0049 PG 10 WC Oncology SC Oncology GA CD9ZK UT WOS:000351460500005 PM 26812429 ER PT J AU Fasciano, KM Souza, PM Braun, I Trevino, K AF Fasciano, Karen M. Souza, Phoebe M. Braun, Ilana Trevino, Kelly TI An Innovative Website in the United States for Meeting the Emotional and Supportive Care Needs of Young Adults with Cancer SO JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY LA English DT Article DE technology; social networking; mental health; peer support; information; supportive care ID SERVICE USE; ONLINE; ADOLESCENT; HEALTH; PSYCHOTHERAPY; COMMUNITY; INTERNET; ISSUES; IMAGE; PEER AB This paper describes the development of an institution-specific website designed to meet the supportive and emotional needs of young adults (18-39 years old) with cancer in the United States. The website contains information about topics of particular interest to young adults, coping skills education, and resources; and has social networking capacity. In a survey of website users, participants reported increased "connectedness'' and variable impact on feelings of sadness, fear, and worry. Recommendations are made for fostering peer interactions, encouraging staff to educate website users around self-monitoring for distress, and incorporating relevant content on the website. C1 [Fasciano, Karen M.; Souza, Phoebe M.; Braun, Ilana] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Fasciano, Karen M.; Braun, Ilana] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Fasciano, Karen M.; Braun, Ilana] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Trevino, Kelly] Weill Cornell Med Coll, Dept Med, New York, NY USA. RP Fasciano, KM (reprint author), Harvard Univ, Dept Psychosocial Oncol & Palliat Care, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Psychiat,Med Sch, 450 Brookline Ave D2-085, Boston, MA 02215 USA. EM kfasciano@partners.org NR 28 TC 0 Z9 0 U1 1 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2156-5333 EI 2156-535X J9 J ADOLESC YOUNG ADUL JI J. Adolesc. Young Adult Oncol. PD MAR PY 2015 VL 4 IS 1 BP 44 EP 49 DI 10.1089/jayao.2014.0035 PG 6 WC Oncology SC Oncology GA CD9ZK UT WOS:000351460500006 PM 26812430 ER PT J AU Jartti, T Nieminen, R Vuorinen, T Lehtinen, P Vahlberg, T Gern, J Camargo, CA Ruuskanen, O AF Jartti, Tuomas Nieminen, Riitta Vuorinen, Tytti Lehtinen, Pasi Vahlberg, Tero Gern, James Camargo, Carlos A., Jr. Ruuskanen, Olli TI Short- and long-term efficacy of prednisolone for first acute rhinovirus-induced wheezing episode SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Bronchiolitis; child; corticosteroid; glucocorticoid; treatment; prednisolone; rhinovirus; virus; wheeze; wheezing ID RESPIRATORY SYNCYTIAL VIRUS; RANDOMIZED CONTROLLED-TRIAL; VIRAL-ETIOLOGY; EARLY-LIFE; ALLERGIC SENSITIZATION; BRONCHIAL EPITHELIUM; ORAL PREDNISOLONE; TRACT INFECTIONS; FOLLOW-UP; CHILDREN AB Background: Rhinovirus-induced wheezing is an important risk factor for recurrent wheezing. There are no randomized controlled trials on the effect of systemic corticosteroids in patients with this disease. Objective: We sought to study the short-and long-term effects of prednisolone treatment of the first acute, moderate-to-severe, rhinovirus-induced wheezing episode in young children. Methods: After confirming rhinovirus from nasopharyngeal aspirate by using PCR, 79 children with a first wheezing episode at age 3 to 23 months were randomized to receive oral prednisolone (first dose of 2 mg/kg, followed by 2 mg/kg/d in 2 divided doses for 3 days) or placebo. The trial was double blind throughout the 12-month follow-up. The primary outcomes were long term: new physician-confirmed wheezing episode within 2 months, number of physician-confirmed wheezing episodes within 12 months, and initiation of regular controller medication for asthma symptoms within 12 months. The primary interaction analysis examined rhinovirus load. Results: Seventy-four patients completed the study (mean age, 13 months; 28% atopic). Long-term outcomes did not differ between groups (all P >= .30). For short-term outcomes, the prednisolone group had less cough, rhinitis, noisy breathing, severe breathing difficulties, and nocturnal respiratory symptoms at home within 2 weeks (all P <.05). The 25 children with greater than 7000 rhinovirus copies/mL (most sensitive cutoff) benefitted from prednisolone in terms of less risk of physician-confirmed recurrence within 2 and 12 months compared with placebo (both P <.05). Conclusions: Prednisolone cannot be routinely recommended for all young children experiencing their first acute, moderate-to-severe, rhinovirus-induced wheezing episode. Prednisolone might be beneficial in a subgroup of children with high viral loads. C1 [Jartti, Tuomas; Nieminen, Riitta; Lehtinen, Pasi; Ruuskanen, Olli] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. [Nieminen, Riitta; Vuorinen, Tytti] Univ Turku, Dept Virol, SF-20500 Turku, Finland. [Vahlberg, Tero] Univ Turku, Dept Biostat, SF-20500 Turku, Finland. [Gern, James] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53706 USA. [Gern, James] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Jartti, T (reprint author), Turku Univ Hosp, Dept Pediat, POB 52, FIN-20520 Turku, Finland. EM tuomas.jartti@utu.fi FU Suomen Akatemia Helsinki, Finland [132595, 114034]; Finnish Medical Foundation, Helsinki, Finland; Sigrid Juselius Foundation, Helsinki, Finland; Foundation for Pediatric Research, Helsinki, Finland; Suomen Kulttuurirahasto, Turku and Helsinki, Finland; Turku University Foundation, Turku, Finland; Paulo Foundation, Helsinki, Finland; Allergy Research Foundation, Helsinki, Finland FX Supported by the Suomen Akatemia (grant nos. 132595 and 114034), Helsinki, Finland; the Finnish Medical Foundation, Helsinki, Finland; the Sigrid Juselius Foundation, Helsinki, Finland; the Foundation for Pediatric Research, Helsinki, Finland; the Suomen Kulttuurirahasto, Turku and Helsinki, Finland; the Turku University Foundation, Turku, Finland; the Paulo Foundation, Helsinki, Finland; and the Allergy Research Foundation, Helsinki, Finland. NR 42 TC 24 Z9 24 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2015 VL 135 IS 3 BP 691 EP U178 DI 10.1016/j.jaci.2014.07.001 PG 17 WC Allergy; Immunology SC Allergy; Immunology GA CD4PF UT WOS:000351065000014 PM 25129681 ER PT J AU Altman, AM Camargo, CA Simons, FER Lieberman, P Sampson, HA Schwartz, LB Zitt, FM Collins, C Tringale, M Wilkinson, M Wood, RA AF Altman, Ashley M. Camargo, Carlos A., Jr. Simons, F. Estelle R. Lieberman, Philip Sampson, Hugh A. Schwartz, Lawrence B. Zitt, F. Myron Collins, Charlotte Tringale, Michael Wilkinson, Marilyn Wood, Robert A. TI Anaphylaxis in America: A national physician survey SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID FOOD-INDUCED ANAPHYLAXIS; ATOPIC-DERMATITIS; KOREAN CHILDREN; ENVIRONMENT; ALLERGY; ASTHMA; LIFE; CARE C1 [Altman, Ashley M.; Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Epidemiol, Boston, MA 02114 USA. [Simons, F. Estelle R.] Univ Manitoba, Dept Pediat & Child Hlth, Sect Allergy & Clin Immunol, Winnipeg, MB R3T 2N2, Canada. [Lieberman, Philip] Univ Tennessee, Coll Med, Dept Internal Med, Germantown, TN USA. [Lieberman, Philip] Univ Tennessee, Coll Med, Dept Pediat, Germantown, TN USA. [Sampson, Hugh A.] Icahn Sch Med Mt Sinai, Div Allergy & Immunol, Dept Pediat, New York, NY 10029 USA. [Schwartz, Lawrence B.] Virginia Commonwealth Univ, Dept Med, Div Rheumatol Allergy & Immunol, Richmond, VA 23298 USA. [Zitt, F. Myron] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Collins, Charlotte; Tringale, Michael] Asthma & Allergy Fdn Amer, Landover, MD USA. [Wilkinson, Marilyn] Abt SRBI Inc, Silver Spring, MD USA. RP Altman, AM (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. EM rwood@jhmi.edu FU NIAID NIH HHS [T32 AI007007] NR 17 TC 4 Z9 4 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2015 VL 135 IS 3 BP 830 EP 833 DI 10.1016/j.jaci.2014.10.049 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA CD4PF UT WOS:000351065000037 PM 25577592 ER PT J AU Normandin, PA AF Normandin, Patricia A. TI PEDIATRIC INFECTIOUS DISEASES SO JOURNAL OF EMERGENCY NURSING LA English DT Article C1 [Normandin, Patricia A.] Tufts Med Ctr, Emergency Dept Staff Nurse, Boston, MA 02111 USA. [Normandin, Patricia A.] Northeastern Univ, Boston, MA 02115 USA. [Normandin, Patricia A.] Brigham & Womens Hosp, Adjunct Nursing Fac, 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. RP Normandin, PA (reprint author), Tufts Med Ctr, Emergency Dept Staff Nurse, Boston, MA 02111 USA. EM pnormandinrn@aol.com NR 3 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 0099-1767 EI 1527-2966 J9 J EMERG NURS JI J. Emerg. Nurs. PD MAR PY 2015 VL 41 IS 2 BP 160 EP 161 DI 10.1016/j.jen.2014.12.008 PG 2 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA CD2IP UT WOS:000350900600023 PM 25770000 ER PT J AU Fanfani, F Boruta, DM Fader, AN Vizza, E Growdon, WB Kushnir, CL Corrado, G Scambia, G Turco, LC Fagotti, A AF Fanfani, Francesco Boruta, David M. Fader, Amanda N. Vizza, Enrico Growdon, Withfiel B. Kushnir, Cristina L. Corrado, Giacomo Scambia, Giovanni Turco, Luigi C. Fagotti, Anna TI Feasibility and Surgical Outcome in Obese Versus Nonobese Patients Undergoing Laparoendoscopic Single-site Hysterectomy: A Multicenter Case-control Study SO JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY LA English DT Article DE Hysterectomy; Laparoscopy; Laparoendoscopic single-site surgery; Obesity; Single site ID ENDOMETRIAL CANCER; LAPAROSCOPIC HYSTERECTOMY; PERIOPERATIVE OUTCOMES; RANDOMIZED-TRIAL; SURGERY; WOMEN AB Objective: To assess the feasibility and perioperative outcomes of laparoendoscopic single-site (LESS) hysterectomy in obese and nonobese women. Design: A multicentric retrospective case-control study (Canadian Task Force II-2). Setting: Catholic University of the Sacred Heart and National Cancer Institute "Regina Elena" (Rome, Italy), Massachusetts General Hospital (Boston, MD), and Johns Hopkins Hospital (Baltimore, MD). Patients: From July 2009 to April 2013, 120 women underwent LESS hysterectomy. Five women (8%) were excluded from the analysis. The remaining 115 women were divided into 2 groups: obese (n = 43, body mass index [BMI] >= 30 kg/m(2)) and nonobese (n = 72, BMI <30 kg/m(2)). Interventions: Total LESS hysterectomies for malignant and premalignant uterine disease or at least for prophylactic intent were performed. Measurements and Main Results: No statistical differences regarding perioperative outcomes were observed between the 2 groups. Conversion to standard laparoscopy occurred in 2 obese (5%) and 2 (5%) nonobese women (p = .62). Conversion to laparotomy occurred in 1 obese (2.3%) and 3 (4.2%) nonobese women (p = .212). The median operative time was 115 minutes (range, 48-300 minutes) in obese and 114 minutes (range, 55-342 minutes) in nonobese women (p = .787). The intraoperative complication rate was 11.6% and 9.6% in obese and nonobese women, respectively (p = .712). The early postoperative complication rate was 6.9% in obese and 4.1% in nonobese women (p = .516). Conclusion: Despite the fact that the present analysis was performed in a relatively small group of patients, this study suggests that obesity (BMI >= 30) does not preclude successful completion of total LESS hysterectomy. Further prospective studies are required to confirm these preliminary data and to clarify potential advantages and disadvantages of LESS in obese women. (C) 2015 AAGL. All rights reserved. C1 [Fanfani, Francesco; Scambia, Giovanni; Turco, Luigi C.] Univ Cattolica Sacro Cuore, Dept Obstet & Gynecol, Div Gynecol Oncol, I-00168 Rome, Italy. [Boruta, David M.; Growdon, Withfiel B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol, Boston, MA USA. [Fader, Amanda N.; Kushnir, Cristina L.] Johns Hopkins Med Inst, Div Gynecol Oncol, Baltimore, MD USA. [Vizza, Enrico; Corrado, Giacomo] Regina Elena Inst Canc Res, Dept Surg Oncol, Gynecol Oncol Unit, Rome, Italy. [Fagotti, Anna] Univ Perugia, St Maria Hosp, Minimally Invas Gynecol, Terni, Italy. RP Fanfani, F (reprint author), Univ Cattolica Sacro Cuore, Dept Obstet & Gynecol, Gynecol Oncol Unit, I-00168 Rome, Italy. EM francesco.fanfani@rm.unicatt.it RI Fanfani, Francesco/Q-1154-2015 OI Fanfani, Francesco/0000-0003-1991-7284 NR 22 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1553-4650 EI 1553-4669 J9 J MINIM INVAS GYN JI J. Mimim. Invasive Gynecol. PD MAR-APR PY 2015 VL 22 IS 3 BP 456 EP 461 DI 10.1016/j.jmig.2014.12.008 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CE0FZ UT WOS:000351481200024 PM 25510981 ER PT J AU Park, ER Smith, KB Merker, VL Muzikansky, A Vranceanu, AM Wang, DL Plotkin, SR AF Park, Elyse R. Smith, Kelly B. Merker, Vanessa L. Muzikansky, Alona Vranceanu, Ana-Maria Wang, Daphne L. Plotkin, Scott R. TI Examining perceived cancer risk among patients with neurofibromatosis type 1 SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Neurofibromatosis; Perceived risk; Neurooncology; Cancer risk; Genetic; Distress ID NERVE SHEATH TUMORS; NF1; PREDICTORS; PERCEPTIONS AB Neurofibromatosis 1 (NF1) is a genetic disorder in which patients are at significantly increased risk for developing malignant peripheral nerve sheath tumors (MPNST) andmalignant gliomas (brain cancer). We sought to develop a measure for assessing perceived risk of developing MPNST and brain cancer among patients with NF1 and to examine patients' perceived risk of developing these cancers. We assessed 112 NF1 patients' perceived risk of developing MPNST and brain cancer using an 8-item scale we developed that yielded two subscales in a principal component analysis (PCA). Linear regression models examined factors associated with perceived risk of malignancy. 33.9 % and 47.3 % of patients disagreed that having NF1 placed them at increased risk for MPNST and brain cancer, respectively. The PCA of the perceived risk items yielded a 2-factor solution with an MPNST and a brain subscale (total scale alpha = 0.90). Level of anxiety was the primary factor associated with perceived risk for both cancers. A significant proportion of NF1 patients underestimate their risk of developing MPNST and brain cancer. Perceived risk was associated with emotional distress, in particular anxiety. Clinicians should actively communicate with NF1 patients about their elevated cancer risk. C1 [Park, Elyse R.; Smith, Kelly B.; Vranceanu, Ana-Maria] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Canc Ctr, Dept Psychiat,Mongan Inst Hlth Policy,Benson Henr, Boston, MA 02114 USA. [Merker, Vanessa L.; Wang, Daphne L.; Plotkin, Scott R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Merker, Vanessa L.; Wang, Daphne L.; Plotkin, Scott R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Muzikansky, Alona] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biostat Div, Boston, MA 02114 USA. RP Park, ER (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Canc Ctr, Dept Psychiat,Mongan Inst Hlth Policy,Benson Henr, 50 Staniford St 907, Boston, MA 02114 USA. EM epark@partners.org OI Merker, Vanessa/0000-0002-4542-5227 NR 33 TC 0 Z9 0 U1 0 U2 1 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 MAR PY 2015 VL 122 IS 1 BP 127 EP 133 DI 10.1007/s11060-014-1689-6 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CD4YD UT WOS:000351091500014 PM 25559686 ER PT J AU Wu, L Du, Y Lok, J Lo, EH Xing, CB AF Wu, Limin Du, Yang Lok, Josephine Lo, Eng H. Xing, Changbong TI Lipocalin-2 enhances angiogenesis in rat brain endothelial cells via reactive oxygen species and iron-dependent mechanisms SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE iron; migration; neurovascular remodeling; reactive oxygen species; stroke; tube formation ID STROKE; INJURY; RECEPTOR; ROLES; MODEL AB Inflammation is a key part of central nervous system pathophysiology. However, inflammatory factors are now thought to have both beneficial and deleterious effects. Here, we examine the hypothesis that lipocalin-2 (LCN2), an inflammatory molecule that can be up-regulated in the distressed central nervous system, may enhance angiogenesis in brain endothelial cells. Adding LCN2 (0.5-2.0 lg/mL) to RBE (Rat brain endothelial cells). 4 rat brain endothelial cells significantly increased matrigel tube formation and scratch migration, and also elevated levels of iron and reactive oxygen species. Cotreatment with a radical scavenger (U83836E), a Nox inhibitor (apocynin) and an iron chelating agent (deferiprone) significantly dampened the ability of LCN2 to enhance tube formation and scratch migration in brain endothelial cells. These findings provide in vitro proof of the concept that LCN2 can promote angiogenesis via iron-and reactive oxygen species-related pathways, and support the idea that LCN2 may contribute to the neurovascular recovery aspects of inflammation. C1 [Wu, Limin; Du, Yang; Lok, Josephine; Lo, Eng H.; Xing, Changbong] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Charlestown, MA 02129 USA. [Wu, Limin; Du, Yang; Lok, Josephine; Lo, Eng H.; Xing, Changbong] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Charlestown, MA 02129 USA. [Wu, Limin; Du, Yang; Lok, Josephine; Lo, Eng H.; Xing, Changbong] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat, Sch Med, Charlestown, MA 02129 USA. [Wu, Limin] Jilin Univ, Hosp 1, Dept Neurol, Changchun 130023, Peoples R China. [Du, Yang] Capital Med Univ, Dept Neurol, Beijing Tiantan Hosp, Beijing, Peoples R China. RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, MGH E 149-2401, Charlestown, MA 02129 USA. EM lo@helix.mgh.harvard.edu FU NIH; AHA; Rappaport Foundation FX The study was supported in part by grants from the NIH, AHA, and the Rappaport Foundation. The authors have no conflicts of interest to declare. NR 22 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2015 VL 132 IS 6 BP 622 EP 628 DI 10.1111/jnc.13023 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CD9BZ UT WOS:000351392800002 PM 25557118 ER PT J AU Doty, RL Nsoesie, MT Chung, IN Osman, A Pawasarat, I Caulfield, J Hurtig, H Silas, J Dubroff, J Duda, JE Ying, GS Tekeli, H Leon-Sarmiento, FE AF Doty, Richard L. Nsoesie, Michael T. Chung, Inna Osman, Allen Pawasarat, Ian Caulfield, Julie Hurtig, Howard Silas, Jonathan Dubroff, Jacob Duda, John E. Ying, Gui-Shuang Tekeli, Hakan Leon-Sarmiento, Fidias E. TI Taste function in early stage treated and untreated Parkinson's disease SO JOURNAL OF NEUROLOGY LA English DT Article DE Parkinson's disease; Taste; Tongue; Dopamine; SPECT imaging; Cranial nerves ID OLFACTORY DYSFUNCTION; BRAIN-STEM; RECEPTORS; RESPONSES; SMELL AB Since brain stem regions associated with early Parkinson's disease (PD) pathology encroach upon those involved in taste function, the ability to taste may be compromised in PD. However, studies on this point have been contradictory. We administered well-validated whole-mouth and regional taste tests that incorporated multiple concentrations of sucrose, citric acid, caffeine, and sodium chloride to 29 early stage PD patients and 29 age-, sex-, and race-matched controls. Electrogustometry was also performed on the anterior tongue. The PD cohort was tested both on and off dopamine-related medications in counterbalanced test sessions. While whole-mouth taste identification test scores for all stimuli were, on average, nominally lower for the PD patients than for the controls, a trend in the opposite direction was noted for the intensity ratings at the lower stimulus concentrations for all stimuli except caffeine. Moreover, regional testing found that PD subjects tended to rate the stimuli, relative to the controls, as more intense on the anterior tongue and less intense on the posterior tongue. No significant associations were evident between taste test scores and UPDRS scores, L-DOPA medication equivalency values, or [Tc-99m]TRODAT-1 SPECT imaging of dopamine transporter uptake within the striatum and associated regions. Our findings suggest that suprathreshold measures of taste function are influenced by PD and that this disease differentially influences taste function on anterior (CN VII) and posterior (CN IX) tongue regions. Conceivably PD-related damage to CN IX releases central inhibition on CN VII at the level of the brainstem, resulting in enhanced taste intensity on the anterior tongue. C1 [Doty, Richard L.; Chung, Inna; Pawasarat, Ian; Caulfield, Julie; Leon-Sarmiento, Fidias E.] Hosp Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Ctr Smell & Taste, Philadelphia, PA 19104 USA. [Nsoesie, Michael T.] Earlham Coll, Dept Biol, Richmond, IN 47374 USA. [Osman, Allen] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. [Hurtig, Howard; Duda, John E.] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Silas, Jonathan] Univ Roehampton, Dept Psychol, London SW15 4JD, England. [Dubroff, Jacob] Univ Penn, Perelman Sch Med, Div Nucl Med & Clin Mol Imaging, Dept Radiol, Philadelphia, PA 19104 USA. [Duda, John E.] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Ying, Gui-Shuang] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ying, Gui-Shuang] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Tekeli, Hakan] Haydarpasa Training Hosp GATA, Dept Neurol, TR-34668 Istanbul, PK, Turkey. RP Doty, RL (reprint author), Hosp Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Ctr Smell & Taste, 5 Ravdin Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. EM richard.doty@uphs.upenn.edu FU USAMRAA [W81XWH-09-1-0467] FX This research was supported by USAMRAA W81XWH-09-1-0467. We thank the following persons for their assistance on this project: Jessica Morton, Megan Blair, Emma Harmon, Thelma McCloskey, Ellen Carson, Nancy Wintering, Jonathan Silas, Dandy Zhu, Zackary Salman, and Kelly Cathey. NR 33 TC 5 Z9 5 U1 2 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD MAR PY 2015 VL 262 IS 3 BP 547 EP 557 DI 10.1007/s00415-014-7589-z PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CE0BX UT WOS:000351469200006 PM 25480568 ER PT J AU Yu, EY Duan, FH Muzi, M Deng, X Chin, BB Alumkal, JJ Taplin, ME Taub, JM Ben Herman, Higano, CS Doot, RK Hartfeil, D Febbo, PG Mankoff, DA AF Yu, Evan Y. Duan, Fenghai Muzi, Mark Deng, Xuan Chin, Bennett B. Alumkal, Joshi J. Taplin, Mary-Ellen Taub, Jina M. Ben Herman Higano, Celestia S. Doot, Robert K. Hartfeil, Donna Febbo, Philip G. Mankoff, David A. TI Castration-Resistant Prostate Cancer Bone Metastasis Response Measured by F-18-Fluoride PET After Treatment with Dasatinib and Correlation with Progression-Free Survival: Results from American College of Radiology Imaging Network 6687 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE F-18-fluoride PET; bone metastases; dasatinib; metastatic castration-resistant prostate cancer ID POSITRON-EMISSION-TOMOGRAPHY; KINASE-ACTIVITY; PHASE-II; SRC; RECOMMENDATIONS; INHIBITION; DOCETAXEL; THERAPY; TRIALS; GROWTH AB F-18-fluoride PET quantitatively images bone metabolism and may serve as a pharmacodynamic assessment for systemic therapy such as dasatinib, a potent SRC kinase inhibitor, with activity in bone. Methods: This was an imaging companion trial (American College of Radiology Imaging Network [ACRIN] 6687) to a multicenter metastatic castration-resistant prostate cancer (CRPC) tissue biomarker-guided therapeutic trial (NCT00918385). Men with bone metastatic CRPC underwent F-18-fluoride PET before and 12 weeks after initiation of dasatinib (100 mg daily). Dynamic imaging was performed over a 15-cm field of view for trial assessments. The primary endpoint was to determine whether changes in F-18-fluoride incorporation in tumor and normal bone occurred in response to dasatinib. Other endpoints included differential effect of dasatinib between F-18-fluoride incorporation in tumor and normal bone, (18)Ffluoride transport in bone metastases, correlation with progressionfree survival (PFS), prostate-specific antigen, and markers of bone turnover. Results: Eighteen participants enrolled, and 17 underwent interpretable baseline F-18-fluoride PET imaging before initiation of dasatinib. Twelve of 17 patients underwent on-treatment PET imaging. Statistically significant changes in response to dasatinib were identified by the SUVmaxavg (average of maximum standardized uptake value [SUVmax] for up to 5 tumors within the dynamic field of view) in bone metastases (P = 0.0002), with a significant differential F-18-fluoride PET response between tumor and normal bone (P, 0.0001). Changes in F-18-fluoride incorporation in bone metastases had borderline correlation with PFS by SUVmaxavg (hazard ratio, 0.91; 95% confidence interval, 0.82-1.00; P = 0.056). Changes by SUVmaxavg correlated with bone alkaline phosphatase (P = 0.0014) but not prostate-specific antigen (P = 0.47). Conclusion: This trial provides evidence of the ability F-18-fluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS. C1 [Yu, Evan Y.; Muzi, Mark; Taub, Jina M.; Higano, Celestia S.] Univ Washington, Seattle, WA 98109 USA. [Duan, Fenghai; Deng, Xuan; Ben Herman] Brown Univ, Sch Publ Hlth, Dept Biostat, Providence, RI 02912 USA. [Duan, Fenghai; Deng, Xuan; Ben Herman] Brown Univ, Sch Publ Hlth, Ctr Stat Sci, Providence, RI 02912 USA. [Chin, Bennett B.] Duke Univ, Durham, NC USA. [Alumkal, Joshi J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Taplin, Mary-Ellen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Doot, Robert K.; Mankoff, David A.] Univ Penn, Philadelphia, PA 19104 USA. [Hartfeil, Donna] Amer Coll Radiol Imaging Network, Philadelphia, PA USA. [Febbo, Philip G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Yu, EY (reprint author), Univ Washington, Sch Med, Div Oncol, Dept Med, 825 Eastlake Ave East,G4-836,Box 358081, Seattle, WA 98109 USA. EM evanyu@uw.edu RI Chin, Bennett/M-6554-2015 OI Chin, Bennett/0000-0002-2907-5968 FU ACRIN; National Cancer Institute [U01 CA080098]; American Recovery and Reinvestment Act of 2009 (ARRA) [U01 CA079778]; Quantitative Imaging Network [U01 CA148131]; WorldCare Clinical, LLC.; DoD 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. The study was supported by ACRIN, which receives funding from the National Cancer Institute through U01 CA080098, under the American Recovery and Reinvestment Act of 2009 (ARRA), U01 CA079778, and Bristol-Myers Squibb. Imaging analysis was supported by the Quantitative Imaging Network U01 CA148131. All patients were accrued at the Department of Defense (DoD) Prostate Cancer Clinical Trials Consortium (UW W81XWH-09-1-0144, Duke W81XWH-09-1-0152, OHSU W81XWH-09-1-0140, DFCI W81XWH-09-1-0150) and Prostate Cancer Foundation Therapy Consortium sites. Fenghai Duan is a paid consultant for WorldCare Clinical, LLC. Evan Y. Yu, Joshi J. Alumkal, Mary-Ellen Taplin, Celestia S. Higano, and Philip G. Febbo are members of the Prostate Cancer Clinical Trials Consortium, sponsored by the DoD. No other potential conflict of interest relevant to this article was reported. NR 26 TC 14 Z9 15 U1 0 U2 3 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 MAR PY 2015 VL 56 IS 3 BP 354 EP 360 DI 10.2967/jnumed.114.146936 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CC8PX UT WOS:000350631700031 PM 25635138 ER PT J AU Lee, SI Catalano, OA Dehdashti, F AF Lee, Susanna I. Catalano, Onofrio A. Dehdashti, Farrokh TI Evaluation of Gynecologic Cancer with MR Imaging, F-18-FDG PET/CT, and PET/MR Imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE Cu-labeled diacetyl-bis (N4-methylthiosemicarbazone) PET; 16 alpha-F-18-fluoro-17 beta-estradiol PET; diffusion weighted imaging; dynamic contrast enhanced MRI; perfusion MRI ID POSITRON-EMISSION-TOMOGRAPHY; INVASIVE CERVICAL-CANCER; ASSESSING TUMOR HYPOXIA; LYMPH-NODE METASTASIS; INTEGRATED FDG PET/CT; ENDOMETRIAL CANCER; OVARIAN-CANCER; MYOMETRIAL INVASION; DIAGNOSTIC-ACCURACY; COMPUTED-TOMOGRAPHY AB MR imaging and F-18-FDG PET/CT play central and complementary roles in the care of patients with gynecologic cancer. Because treatment often requires combinations of surgery, radiotherapy, and chemotherapy, imaging is central to triage and to determining prognosis. This article reviews the use of the 2 imaging modalities in the initial evaluation of 3 common cancers: uterine cervical, uterine endometrial, and epithelial ovarian. Imaging features that affect management are highlighted, as well as the relative strengths and weaknesses of the 2 modalities. Use of imaging after initial therapy to assess for recurrence and to plan salvage therapy is described. Newer functional and molecular techniques in MR imaging and PET are evaluated. Finally, we describe our initial experience with PET/MR imaging, an emerging technology that may prove to be a mainstay in personalized gynecologic cancer care. C1 [Lee, Susanna I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Catalano, Onofrio A.] Univ Naples Parthenope, Dept Radiol, Naples, Italy. [Catalano, Onofrio A.] SDN Ist Ric Diagnost Nucl, Naples, Italy. [Dehdashti, Farrokh] Washington Univ, Mallinckrodt Inst Radiol, Dept Nucl Med, St Louis, MO USA. RP Lee, SI (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White 270, Boston, MA 02114 USA. EM slee0@partners.org NR 58 TC 15 Z9 15 U1 3 U2 22 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 MAR PY 2015 VL 56 IS 3 BP 436 EP 443 DI 10.2967/jnumed.114.145011 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CC8PX UT WOS:000350631700044 PM 25635136 ER PT J AU Stephenson, NA Holland, JP Kassenbrock, A Yokell, DL Livni, E Liang, SH Vasdev, N AF Stephenson, Nickeisha A. Holland, Jason P. Kassenbrock, Alina Yokell, Daniel L. Livni, Eli Liang, Steven H. Vasdev, Neil TI Iodonium Ylide-Mediated Radiofluorination of F-18-FPEB and Validation for Human Use SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE F-18-FPEB; mGlu(5); iodonium ylide; PET; fluorination ID PET; METABOTROPIC-GLUTAMATE-RECEPTOR-SUBTYPE-5; RADIOSYNTHESIS; TRACER; SALTS; F-18 AB Translation of new methodologies for labeling nonactivated aromatic molecules with F-18 remains a challenge. Here, we report a one-step, regioselective, metal-free F-18-labeling method that uses a hypervalent iodonium(III) ylide precursor, to prepare the radiopharmaceutical F-18-3- fluoro-5-[(pyridin-3-yl) ethynyl] benzonitrile (F-18-FPEB). Methods: Automated radiosynthesis of 18F-FPEB was achieved by reaction of the ylide precursor (4 mg) with F-18-Et4NF in dimethylformamide at 80 degrees C for 5 min and formulated for injection within 1 h. Results: F-18-FPEB was synthesized in 20% +/- 5% (n 5 3) uncorrected radiochemical yields relative to F-18-fluoride, with specific activities of 666 +/- 51.8 GBq (18 +/- 1.4 Ci)/mu mol at the end of synthesis and was validated for human use. Conclusion: Radiofluorination of iodonium (III) ylides proved to be an efficient radiosynthetic strategy for synthesis of F-18-labeled radiopharmaceuticals. C1 [Stephenson, Nickeisha A.; Kassenbrock, Alina; Yokell, Daniel L.; Livni, Eli; Liang, Steven H.; Vasdev, Neil] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Stephenson, Nickeisha A.; Holland, Jason P.; Livni, Eli; Liang, Steven H.; Vasdev, Neil] Harvard Univ, Dept Radiol, Sch Med, Boston, MA 02114 USA. RP Vasdev, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,White 427, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu FU Alzheimer's Drug Discovery Foundation; Australian National Science and Technology Organisation 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. We thank the Alzheimer's Drug Discovery Foundation as well as Dr. Ivan Greguric and the Australian National Science and Technology Organisation for financial support. No other potential conflict of interest relevant to this article was reported. NR 20 TC 16 Z9 16 U1 3 U2 15 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 MAR PY 2015 VL 56 IS 3 BP 489 EP 492 DI 10.2967/jnumed.114.151332 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CC8PX UT WOS:000350631700052 PM 25655630 ER PT J AU Thrall, JH AF Thrall, James H. TI Misinterpretation of F-18-FDG Studies in Oncology SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter ID PET/CT C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, 25 New Chardon St, Boston, MA 02114 USA. EM jthrall@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 2015 VL 56 IS 3 BP 494 EP 494 DI 10.2967/jnumed.114.153064 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CC8PX UT WOS:000350631700053 PM 25635135 ER PT J AU Gallagher, MW Brown, TA AF Gallagher, Matthew W. Brown, Timothy A. TI Bayesian Analysis of Current and Lifetime Comorbidity Rates of Mood and Anxiety Disorders in Individuals with Posttraumatic Stress Disorder SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE PTSD; Anxiety; Depression; Assessment/Diagnosis; Bayesian analysis ID DSM-IV ANXIETY; PROLONGED EXPOSURE; CLASSIFICATION; VETERANS; PATTERNS AB Although posttraumatic stress disorder (PTSD) is no longer considered an anxiety disorder in DSM-5, previous research has indicated high rates of comorbid anxiety and mood disorders in individuals with PTSD. The goal of the present study was to build upon previous examinations of diagnostic comorbidity by using Bayesian methods of estimating current and lifetime comorbidity rates to determine more precise estimates of the proportion of individuals in a clinical sample with PTSD that also meet criteria for various emotional disorders. Two hundred and fifty three individuals with a current or lifetime diagnosis of PTSD underwent a comprehensive assessment of current and lifetime emotional disorders. Bayesian statistical techniques were then used to calculate credibility intervals for the current and lifetime comorbidity rates of emotional disorders. The Bayesian analyses used informative priors based on previous comorbidity findings. The median number of current emotional disorders was two and the median number of lifetime comorbid emotional disorders was three. Credibility intervals indicated that social phobia and major depressive disorder were the most common current and lifetime comorbid emotional disorders. The proportion of individuals with lifetime comorbidity rates were very high for both any lifetime anxiety disorder (0.91, 95 % CI 0.88: 0.94) and any lifetime depressive disorder (0.90, 95 % CI 0.86: 0.93). Together these results indicate that despite the separation from the anxiety disorders in DSM-5, the vast majority of individuals with PTSD will present with one or more emotional disorders. Implications for the assessment and treatment of PTSD are discussed. C1 [Gallagher, Matthew W.] VA Boston Healthcare Syst 116B 2, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Gallagher, Matthew W.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Brown, Timothy A.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Gallagher, MW (reprint author), VA Boston Healthcare Syst 116B 2, Behav Sci Div, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA. EM mwg@bu.edu FU National Institute of Mental Health [R01 MH039096] FX This research was supported by Grant R01 MH039096 (PI: Timothy A. Brown) from the National Institute of Mental Health. NR 28 TC 2 Z9 2 U1 3 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD MAR PY 2015 VL 37 IS 1 BP 60 EP 66 DI 10.1007/s10862-014-9436-z PG 7 WC Psychology, Clinical SC Psychology GA CD7ZZ UT WOS:000351316200006 PM 26166944 ER PT J AU Young, MA Hutman, P Enggasser, JL Meesters, Y AF Young, Michael A. Hutman, Paul Enggasser, Justin L. Meesters, Ybe TI Assessing Usual Seasonal Depression Symptoms: The Seasonality Assessment Form SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Seasonal affective disorder; Seasonality; Depression; Symptom assessment; Factor analysis; Impairment ID AFFECTIVE-DISORDER; WINTER DEPRESSION; INVENTORY-II; MOOD; BEHAVIOR; VULNERABILITY; EPIDEMIOLOGY; MODELS; ONSET AB This paper presents findings on the psychometric properties of a new measure of the usual severity of winter symptomatology commonly found in Seasonal Affective Disorder (SAD), the Seasonality Assessment Form (SAF). Many existing SAD-related measures focus on diagnostic screening, include a limited range of symptoms or are revisions of standard self-report depression measures that have not undergone psychometric evaluation. The SAF was developed to address these limitations, in particular to include the full range of cognitive, affective, and vegetative symptoms that are in DSM criteria for a depressive episode. Data came from a diverse sample of 741 students, community members recruited for having winter vegetative changes, and diagnosed SAD patients. The SAF total score, as well as vegetative and cognitive/affective subscales, exhibited good internal consistency and convergent and construct validity. The SAF demonstrated a bifactor structure, suggesting a large global severity factor and additional subfactors related to appetite/weight and negative thought content. Symptomatic participants reported relatively high levels of impairment in daily activities, in particular avoiding or delaying doing daily tasks. In sum, the SAF appears to be a concise, comprehensive, reliable, and valid measure of SAD symptom severity. In addition, its instructions can be revised easily to provide parallel forms for assessing the current episode or recent weeks. C1 [Young, Michael A.; Hutman, Paul] IIT, Dept Psychol, Chicago, IL 60616 USA. [Enggasser, Justin L.] VA Boston Healthcare Syst, Boston, MA USA. [Enggasser, Justin L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Meesters, Ybe] Univ Groningen, Univ Med Ctr Groningen, Univ Ctr Psychiat, NL-9713 AV Groningen, Netherlands. RP Young, MA (reprint author), IIT, Dept Psychol, 3105 South Dearborn,Room 252, Chicago, IL 60616 USA. EM youngm@iit.edu NR 38 TC 2 Z9 2 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD MAR PY 2015 VL 37 IS 1 BP 112 EP 121 DI 10.1007/s10862-014-9440-3 PG 10 WC Psychology, Clinical SC Psychology GA CD7ZZ UT WOS:000351316200011 ER PT J AU Gros, DF Farmer, AS McCabe, RE Antony, MM AF Gros, Daniel F. Farmer, Antonina S. McCabe, Randi E. Antony, Martin M. TI Psychometric Evaluation of the Multidimensional Assessment of Social Anxiety Before and After Cognitive Behavioral Therapy for Social Anxiety Disorder SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Multidimensional Assessment of Social Anxiety; MASA; Social anxiety disorder; Social phobia; Transdiagnostic; Hybrid model ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; PHOBIA INVENTORY; SYMPTOM OVERLAP; MOOD DISORDERS; DEPRESSION; MODEL; CLASSIFICATION; COMORBIDITY; VERSION AB Due to ongoing criticism of the current diagnostic system, hybrid models of psychopathology, involving the combination of the categorical approach to diagnoses with shared symptom dimensions that are common across various disorders, have received increasing attention in the literature for the depressive and anxiety disorders. One of the few empirically-derived hybrid models was recently developed for social anxiety disorder (SOC) and subsequently led to a self-report measure entitled the Multidimensional Assessment of Social Anxiety (MASA). Although initial support has been provided for the psychometric properties of the MASA, additional research is needed. The present study investigated the internal consistency, convergent and discriminant validity, and sensitivity to detect treatment changes of the MASA scales in 116 participants with SOC that completed the measure at pretreatment and posttreatment during a trial of group cognitive behavioral therapy (CBT) for SOC. The MASA scales demonstrated acceptable sensitivity to detect symptom changes during treatment, convergent validity with related measures of SOC, and internal consistency. In addition, the observed pattern of symptom changes across the MASA scales appeared to be most consistent with the goals/techniques involved in CBT for SOC (e.g., largest improvements in behavioral avoidance; smallest improvements in substance use). Together, these findings provide additional support for psychometric properties of the MASA scales as well as the growing movement towards transdiagnostic assessment and treatment practices. C1 [Gros, Daniel F.; Farmer, Antonina S.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.; Farmer, Antonina S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [McCabe, Randi E.] St Josephs Healthcare, Anxiety Treatment & Res Ctr, Hamilton, ON, Canada. [McCabe, Randi E.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. [Antony, Martin M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. RP Gros, DF (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU Department of Veteran Affairs Clinical Sciences Research and Development Career Development Award [CX000845] FX This study is supported by Department of Veteran Affairs Clinical Sciences Research and Development Career Development Award CX000845 (PI: Gros), as well as with resources and the use of facilities at the Ralph H. Johnson VAMC. 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. NR 37 TC 0 Z9 0 U1 4 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD MAR PY 2015 VL 37 IS 1 BP 144 EP 152 DI 10.1007/s10862-014-9443-0 PG 9 WC Psychology, Clinical SC Psychology GA CD7ZZ UT WOS:000351316200014 ER PT J AU Farabaugh, A Nyer, M Holt, D Baer, L Petrie, S DiPierro, M Nierenberg, A Pedrelli, P Cusin, C Fava, M Mischoulon, D AF Farabaugh, Amy Nyer, Maren Holt, Daphne Baer, Lee Petrie, Samuel DiPierro, Moneika Nierenberg, Andrew Pedrelli, Paola Cusin, Cristina Fava, Maurizio Mischoulon, David TI Screening for Suicide Risk in the College Population SO JOURNAL OF RATIONAL-EMOTIVE AND COGNITIVE-BEHAVIOR THERAPY LA English DT Article DE Suicidality; College students; Beck depression inventory; Suicidal Behaviors Questionnaire-Revised; Screening tool ID RATING-SCALES; BEHAVIORS QUESTIONNAIRE; EVENTUAL SUICIDE; UNITED-STATES; IDEATION; DEPRESSION; STUDENTS; HOPELESSNESS; HEALTH; PREDICTORS AB Suicide is the third leading cause of death in college students, but there is limited consensual evidence to guide clinicians' assessment and management of suicide. The aim of the current study was to assess the capability of a simple and practical measure, the Beck Depression Inventory (BDI) suicide item, to identify college students at high risk of suicide. Exploration of this research question could have important implications in this vulnerable population for identifying those at risk for suicide. Six-hundred-and-fifty-seven college students participated in a mental health screening and completed the BDI and the Suicidal Behaviors Questionnaire-Revised (SBQ-R), which is a detailed measure of suicide risk. We dichotomized the BDI suicide item, which measures suicidal ideation within the past week (presence vs. absence of suicidal ideation) as well as the SBQ-R total score (low vs. high risk of suicide). We computed the kappa statistic for the examination of agreement between these two measures. The kappa coefficient for the BDI suicide item and the SBQ-R was 0.57 for dichotomized scores. The BDI suicide item had a positive predictive value of 74 %, and a negative predictive value of 93 %. In a hierarchical linear regression, the BDI suicide item alone significantly predicted elevated scores on the SBQ-R [Chi square (1) = 128.427, p < 0.001]. These results suggest that affirmative responses on the single BDI suicide item indicate elevated suicide risk. However this single item screening approach will miss some at-risk students. C1 [Farabaugh, Amy; Nyer, Maren; Holt, Daphne; Baer, Lee; Petrie, Samuel; DiPierro, Moneika; Nierenberg, Andrew; Pedrelli, Paola; Cusin, Cristina; Fava, Maurizio; Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Farabaugh, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM afarabaugh@mgh.harvard.edu FU Jed Foundation FX We would like to acknowledge the Jed Foundation for their support for this study. NR 51 TC 2 Z9 2 U1 7 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9085 EI 1573-6563 J9 J RATION-EMOT COGN-B JI J. Ration.-Emot. Cogn.-Behav. Ther. PD MAR PY 2015 VL 33 IS 1 BP 78 EP 94 DI 10.1007/s10942-014-0203-6 PG 17 WC Psychology, Clinical SC Psychology GA CD7TF UT WOS:000351294600005 ER PT J AU Dana, AN Bauman, WA AF Dana, Ali N. Bauman, William A. TI Bacteriology of pressure ulcers in individuals with spinal cord injury: What we know and what we should know SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Review DE Pressure ulcer; Spinal cord injury; Bacteria; Bacteriology; Wound care ID RESISTANT STAPHYLOCOCCUS-AUREUS; HUMAN SKIN MICROBIOTA; CHRONIC WOUNDS; PSEUDOMONAS-AERUGINOSA; KLEBSIELLA-PNEUMONIAE; DECUBITUS ULCERS; NASAL COLONIZATION; MOLECULAR ANALYSIS; MRSA COLONIZATION; INFECTIONS AB Individuals with spinal cord injury (SCI) are at increased risk for the development of pressure ulcers. These chronic wounds are debilitating and contribute to prolonged hospitalization and worse medical outcome. However, the species of bacteria and the role that specific species may play in delaying the healing of chronic pressure ulcers in the SCI population has not been well characterized. This study will review the literature regarding what is known currently about the bacteriology of pressure ulcers in individuals with SCI. An electronic literature search of MEDLINE (1966 to February 2014) was performed. Eleven studies detailing bacterial cultures of pressure ulcers in the SCI population met inclusion criteria and were selected for review. Among these studies, bacterial cultures were often polymicrobial with both aerobic and anaerobic bacteria identified with culture techniques that varied significantly. The most common organisms identified in pressure ulcers were Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, and Enterococcus faecalis. In general, wounds were poorly characterized with minimal to no physical description and/or location provided. Our present understanding of factors that may alter the microbiome of pressure ulcers in individuals with SCI is quite rudimentary, at best. Well-designed studies are needed to assess appropriate wound culture technique, the impact of bacterial composition on wound healing, development of infection, and the optimum medical and surgical approaches to wound care. C1 [Dana, Ali N.] James J Peters Vet Affairs Med Ctr, Dermatol Serv, Bronx, NY 10468 USA. [Dana, Ali N.] Columbia Univ, Dept Dermatol, Sch Med, New York, NY 10027 USA. [Bauman, William A.] James J Peters Vet Affairs Med Ctr, Dept Vet Affairs Rehabil Res & Dev Serv, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY 10468 USA. [Bauman, William A.] James J Peters Vet Affairs Med Ctr, Med Serv, Bronx, NY 10468 USA. [Bauman, William A.] Ichan Sch Med Mt Sinai, Dept Med & Rehabil Med, New York, NY USA. RP Dana, AN (reprint author), James J Peters Vet Affairs Med Ctr, Dermatol Serv, Suite 2F,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Ali.Dana.@va.gov FU James J. Peters Veterans Affairs Medical Center; Department of Veterans Affairs Rehabilitation Research and Development Service [B2468-C, B4162-C] FX Support for this work was provided by the James J. Peters Veterans Affairs Medical Center and the Department of Veterans Affairs Rehabilitation Research and Development Service (#B2468-C, #B4162-C) and the James J. Peters Veterans Affairs Medical Center. NR 82 TC 4 Z9 4 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD MAR PY 2015 VL 38 IS 2 BP 147 EP 160 DI 10.1179/2045772314Y.0000000234 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA CD4RX UT WOS:000351072300005 PM 25130374 ER PT J AU Roberts, ME Nargiso, JE Gaitonde, LB Stanton, CA Colby, SM AF Roberts, Megan E. Nargiso, Jessica E. Gaitonde, Linda Brazil Stanton, Cassandra A. Colby, Suzanne M. TI Adolescent Social Networks: General and Smoking-Specific Characteristics Associated With Smoking SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID TIMELINE FOLLOW-BACK; SUBSTANCE USE; CIGARETTE-SMOKING; TOBACCO CONTROL; SUPPORT; HEALTH; CESSATION; SMOKERS; VALIDATION; BEHAVIORS AB Objective: Converging lines of research suggest that adolescents' smoking behaviors are strongly influenced by the characteristics of their social network and the social processes their network facilitates. The primary goal of this study was to conduct a detailed comparison of the social networks of adolescent smokers and nonsmokers to determine what aspects relate the most to smoking status. A secondary goal was to conduct within-group analyses to examine relationships between key measures of behavior-specific social support and (a) smoking susceptibility among nonsmokers, and (b) readiness to quit smoking among smokers. Method: A matched sample of 190 adolescent smokers and nonsmokers (M-age = 16.8 years; 51% female) completed a questionnaire in which they nominated and reported on up to 10 important people in their lives. This measure allowed us to examine adolescents' overall networks (both peers and family) and to investigate numerous aspects, including general network characteristics (e.g., size of network, average contact with network members), social support (e.g., importance of people in the network), and the pervasiveness of smoking in the network (e.g., percentage of smoking peers). Results: The pervasiveness of smoking in adolescents' social network was the strongest distinguisher of smokers versus nonsmokers. In addition, behavior-specific social support was strongly associated with susceptibility to initiate smoking among nonsmokers and readiness to quit among smokers. Conclusions: This research offers insight into potential targets for prevention and early intervention by demonstrating how social networks can both promote and attenuate risk for smoking. C1 [Roberts, Megan E.; Colby, Suzanne M.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Roberts, Megan E.] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. [Gaitonde, Linda Brazil; Colby, Suzanne M.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Stanton, Cassandra A.] Georgetown Univ Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Nargiso, Jessica E.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Stanton, Cassandra A.] WESTAT Corp, Rockville, MD 20850 USA. RP Roberts, ME (reprint author), Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. EM Roberts.1558@osu.edu FU National Institute on Drug Abuse [1R01 DA16737, T32 DA016184]; National Cancer Institute [K07CA091831, P30CA051008] FX This research was supported by National Institute on Drug Abuse Grants 1R01 DA16737 and T32 DA016184 and National Cancer Institute Grants K07CA091831 and P30CA051008. NR 60 TC 5 Z9 5 U1 2 U2 10 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAR PY 2015 VL 76 IS 2 BP 247 EP 255 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA CD6HF UT WOS:000351189500009 PM 25785800 ER PT J AU Dodd, GD Allen, B Birzniek, D Boland, GW Brink, JA Dreyer, KJ Khandheria, P Kruskal, JB Ricci, P Seibert, JA Zane, R AF Dodd, Gerald D., III Allen, Bibb, Jr. Birzniek, Derek Boland, Giles W. Brink, James A. Dreyer, Keith J. Khandheria, Paras Kruskal, Jonathan B. Ricci, Peter Seibert, J. Anthony Zane, Richard TI Reengineering the Radiology Enterprise: A Summary of the 2014 Intersociety Committee Summer Conference SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Intersociety Committee; Intersociety Committee Summer Conference; ACR; health care reform; Patient Protection and Affordable Care Act AB The current initiative to reform health care from both a quality and a cost perspective has already had a profound impact on the radiology enterprise. We have seen a decrease in the utilization of imaging studies, a reduction in reimbursement, a declining payer mix, shrinking incomes, a proliferation of performance indices, creation of radiology mega-groups, growth of national radiology companies, and increasing turf incursions. Our cheese is clearly on the move, and we must take action to reengineer the radiology enterprise. In keeping with general health care reform, we must be patient-centric, data driven, and outcome based. We must create a radiology enterprise that adheres to the value equation of providing the highest quality health care, for the lowest possible cost, for all citizens. C1 [Dodd, Gerald D., III] Univ Colorado, Dept Radiol, Aurora, CO 80045 USA. [Allen, Bibb, Jr.] Trinity Med Ctr, Birmingham, AL USA. [Birzniek, Derek] Univ Colorado Hlth Syst, Aurora, CO USA. [Boland, Giles W.; Brink, James A.; Dreyer, Keith J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Khandheria, Paras] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Kruskal, Jonathan B.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Ricci, Peter] Radiol Imaging Associates, Englewood, CO USA. [Seibert, J. Anthony] Univ Calif Davis Hlth Syst, Dept Radiol, Sacramento, CA USA. [Zane, Richard] Univ Colorado, Dept Emergency Med, Aurora, CO USA. RP Dodd, GD (reprint author), Univ Colorado, Sch Med, Dept Radiol, Mail Stop L954,12401 E 17th Ave,POB 6510, Aurora, CO 80045 USA. EM gerald.dodd@ucdenver.edu RI bebarta, vikhyat/K-3476-2015; OI Ricci, Peter/0000-0002-9273-7346 NR 34 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAR PY 2015 VL 12 IS 3 BP 228 EP 234 DI 10.1016/j.jacr.2014.11.022 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD3ZD UT WOS:000351021500007 PM 25743920 ER PT J AU Zhang, D Savage, CA Li, XH Liu, B AF Zhang, Da Savage, Cristy A. Li, Xinhua Liu, Bob TI Data-Driven CT Protocol Review and Management-Experience From a Large Academic Hospital SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE CT protocol review; informatics; text matching; automation ID OPTIMIZATION AB Purpose: Protocol review plays a critical role in CT quality assurance, but large numbers of protocols and inconsistent protocol names. on scanners and in exam records make thorough protocol review formidable. In this investigation, we report on a data-driven cataloging, process that can be used to assist in the reviewing and management of CT protocols. Methods: We collected lists of scanner protocols, as well as 18 months of recent exam records, for 10 clinical scanners. We developed computer algorithms to automatically deconstruct the protocol names on the scanner and in the exam records into core names and descriptive components. Based on the core names, we were able to group the scanner protocols into a much smaller set of "core protocols," and to easily link exam records with the scanner protocols. We calculated the percentage of usage for each core protocol, from which the most heavily used protocols were identified. Results: From the percentage-of-usage data, we found that, on average, 18, 33, and 49 core protocols per scanner covered 80%, 90%, and 95%, respectively, of all exams. These numbers are one order of magnitude smaller than the typical numbers of protocols that are loaded on a scanner (200-300, as reported in the literature). Duplicated, outdated, and rarely used protocols on the scanners were easily pinpointed in the cataloging process. Conclusions: The data-driven cataloging process can facilitate the task of protocol review. C1 [Zhang, Da; Li, Xinhua; Liu, Bob] Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA. [Zhang, Da; Li, Xinhua; Liu, Bob] Massachusetts Gen Hosp, Webster Ctr Adv Res & Educ Radiat, Dept Radiol, Boston, MA 02114 USA. [Savage, Cristy A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Zero Emerson Pl,Suite 3A, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 11 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAR PY 2015 VL 12 IS 3 BP 267 EP 272 DI 10.1016/j.jacr.2014.10.006 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD3ZD UT WOS:000351021500013 PM 25577405 ER PT J AU Swan, JS Kong, CY Hur, C Halpern, EF Itauma, O Williams, O Motazedi, T Lee, JM AF Swan, J. Shannon Kong, Chung Yin Hur, Chin Halpern, Elkan F. Itauma, Omosalewa Williams, Olubunmi Motazedi, Tina Lee, Janie M. TI Comparing Morbidities of Testing With a New Index: Screening Colonoscopy Versus Core-Needle Breast Biopsy SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Process assessment; quality of life; patient preference; health status index; diagnostic testing ID PROCESS UTILITY; HEALTH-CARE; PATIENT; MULTIATTRIBUTE; RESPONSIVENESS; PREFERENCES; OUTCOMES; SYSTEM AB Purpose: Focusing on outcomes of care alone may be too restrictive. Patients can experience morbidity that is important to them from health care processes themselves. However, many processes, such as testing and screening, have been little evaluated. This study's purpose was to assess the construct validity of a new preference-based index, the Testing Morbidities Index (TMI), by comparing two common cancer-related procedures in prior publications: screening colonoscopy and core-needle breast biopsy. Methods: Women evaluating their breast biopsies (n = 100) were compared with men and women who had undergone screening colonoscopy (n = 109) after both groups completed the TMI. The TMI addresses physical and mental or emotional quality of life affected by test-specific aspects occurring before, during, or after any test. It has 7 domains and survey items. TMI scores can be scaled in various ways, including multi-attribute value theory based patient or societal preferences, where 0 = dead and 1.0 = full health, as used here. Results: There was significantly greater morbidity from breast biopsy (mean, 0.84) than from screening colonoscopy (mean, 0.88) comparing overall TMI preference scores (P < .0001). Breast biopsy showed significantly worse morbidity (P = .005 to P < .0001) in most domains. Pain or discomfort before testing was worse for colonoscopy because of bowel preparation. The TMI showed no floor effect and an acceptable ceiling effect. Conclusions: The TMI provides the first objective evidence comparing the morbidity of one cancer-related testing procedure with another. The TMI may be useful in assessments of medical care processes informative to institutions and imaging departments, shared decision-making scenarios, and economic analyses. Copyright (C) 2015 American College of Radiology C1 [Swan, J. Shannon; Kong, Chung Yin; Hur, Chin; Halpern, Elkan F.; Itauma, Omosalewa; Williams, Olubunmi; Motazedi, Tina; Lee, Janie M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Swan, J. Shannon; Kong, Chung Yin; Hur, Chin; Halpern, Elkan F.; Lee, Janie M.] Harvard Univ, Sch Med, Boston, MA USA. RP Swan, JS (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM shannon@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 FU American Cancer Society [114130-RSGHP-07-266-01-CPHPS]; Massachusetts General Hospital Executive Committee on Research Bridge Fund [1200-218421] FX This study was supported by the American Cancer Society (114130-RSGHP-07-266-01-CPHPS) and the Massachusetts General Hospital Executive Committee on Research Bridge Fund (1200-218421). NR 26 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAR PY 2015 VL 12 IS 3 BP 295 EP 301 DI 10.1016/j.jacr.2014.08.014 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD3ZD UT WOS:000351021500019 PM 25441485 ER PT J AU Magnani, G Bonaca, MP Braunwald, E Dalby, AJ Fox, KAA Murphy, SA Nicolau, JC Ophuis, TO Scirica, BM Spinar, J Theroux, P Morrow, DA AF Magnani, Giulia Bonaca, Marc P. Braunwald, Eugene Dalby, Anthony J. Fox, Keith A. A. Murphy, Sabina A. Nicolau, Jose Carlos Ophuis, Ton Oude Scirica, Benjamin M. Spinar, Jindrich Theroux, Pierre Morrow, David A. TI Efficacy and Safety of Vorapaxar as Approved for Clinical Use in the United States SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE antiplatelet therapy; atherosclerosis; myocardial infarction; peripheral arterial disease; secondary prevention; vorapaxar ID ACUTE CORONARY SYNDROMES; THROMBIN-RECEPTOR ANTAGONIST; SECONDARY PREVENTION; ISCHEMIC-STROKE; 50 TRIAL; CLOPIDOGREL; ASPIRIN; EVENTS AB Background-Vorapaxar is a protease-activated receptor-1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA). Methods and Results-We examined the efficacy and safety of vorapaxar in the intended use population, considering 20 170 patients randomized in the multinational, double-blinded, placebo-controlled TRA 20P-TIMI 50 trial. Of these, 16 897 qualified with a history of MI in the prior 2 weeks to 1 year and 3273 with PAD. At baseline 97% of the patients were treated with aspirin, 71% with a thienopyridine, and 93% a statin. At 3 years, the endpoint of CV death, MI, or stroke was significantly reduced with vorapaxar compared with placebo (7.9% versus 9.5%, HR, 0.80; 95% CI 0.73 to 0.89; P<0.001). Vorapaxar also significantly reduced the composite of CV death, MI, stroke, and urgent coronary revascularization (10.1% versus 11.8%, HR, 0.83; 95% CI 0.76 to 0.90; P<0.001), as well as the rate of CV death or MI (P<0.001). The safety endpoint of GUSTO moderate or severe bleeding, was increased in the vorapaxar group (3.7 versus 2.4, HR, 1.55; 95% CI 1.30 to 1.86, P<0.001). Intracranial bleeding (ICH) was 0.6% versus 0.4%, P=0.10 with vorapaxar versus placebo, with fatal bleeding 0.2% versus 0.2%; P=0.70. Conclusions-In patients with prior MI or PAD who have not had a previous stroke or TIA, vorapaxar added to standard therapy is effective for long-term secondary prevention of thrombotic CV events, while increasing moderate or severe bleeding. C1 [Magnani, Giulia; Bonaca, Marc P.; Braunwald, Eugene; Murphy, Sabina A.; Scirica, Benjamin M.; Morrow, David A.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Magnani, Giulia; Bonaca, Marc P.; Braunwald, Eugene; Murphy, Sabina A.; Scirica, Benjamin M.; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Dalby, Anthony J.] Milpark Hosp, Johannesburg, South Africa. [Fox, Keith A. A.] Univ Edinburgh, Cardiovasc Res, Edinburgh, Midlothian, Scotland. [Nicolau, Jose Carlos] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. [Ophuis, Ton Oude] Canisius Wilhelmina Hosp, Nijmegen, Netherlands. [Spinar, Jindrich] Masaryk Univ, Univ Hosp Brno, Brno, Czech Republic. [Theroux, Pierre] Montreal Heart Inst, Montreal, PQ, Canada. [Theroux, Pierre] Univ Montreal, Montreal, PQ H3C 3J7, Canada. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org RI Nicolau, Jose/E-1487-2012 FU Merck and Co FX TRA 20 P-TIMI 50 was funded by Merck and Co. NR 13 TC 24 Z9 26 U1 0 U2 7 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 MAR PY 2015 VL 4 IS 3 AR e001505 DI 10.1161/JAHA.114.001505 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0TV UT WOS:000351520300011 PM 25792124 ER PT J AU Murabito, JM Pedley, A Massaro, JM Vasan, RS Esliger, D Blease, SJ Hoffman, U Fox, CS AF Murabito, Joanne M. Pedley, Alison Massaro, Joseph M. Vasan, Ramachandran S. Esliger, Dale Blease, Susan J. Hoffman, Udo Fox, Caroline S. TI Moderate-to-Vigorous Physical Activity With Accelerometry is Associated With Visceral Adipose Tissue in Adults SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE accelerometry; physical activity; visceral adipose tissue ID LIFE-STYLE FACTORS; SEDENTARY BEHAVIOR; INSULIN-RESISTANCE; ACTIVITY PATTERNS; OBESITY; FAT; WOMEN; HEART; HEALTH; RISK AB Background-We examined the relation between objectively measured physical activity with accelerometry and subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in a community-based sample. Methods and Results-We evaluated 1249 participants of the Framingham Third Generation and Omni II cohorts (mean age 51.7 years, 47% women) who underwent assessment of moderate-to-vigorous physical activity (MVPA) with accelerometry over 5 to 7 days, and multi-detector computed tomography for measurement of SAT and VAT volume; fat attenuation was estimated by SAT and VAT hounsfield units (HU). In women, higher levels of MVPA were associated with decreased SAT (P<0.0001) and VAT volume (P<0.0001). The average decrement in VAT per 30 minute/day increase in MVPA was -453 cm(3) (95% CI-574, -331). The association was attenuated but persisted upon adjustment for BMI (-122 cm(3), P=0.002). Higher levels of MVPA were associated with higher SAT HU (all P <= 0.01), a marker of fat quality, even after adjustment for SAT volume. Similar findings were observed in men but the magnitude of the association was less. Sedentary time was not associated with SAT or VAT volume or quality in men or women. Conclusions-MVPA was associated with less VAT and SAT and better fat quality. C1 [Murabito, Joanne M.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med,Sect Prevent Med, Boston, MA 02118 USA. [Murabito, Joanne M.; Pedley, Alison; Massaro, Joseph M.; Vasan, Ramachandran S.; Blease, Susan J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. [Esliger, Dale] Univ Loughborough, Sch Sport Exercise & Hlth Sci, Loughborough, Leics, England. [Hoffman, Udo] Dept Cardiac MR PET CT, Boston, MA USA. [Hoffman, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA USA. [Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Fox, Caroline S.] Div Endocrinol, Boston, MA USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Murabito, JM (reprint author), 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM murabito@bu.edu FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; [R01AG047645] FX The National Heart, Lung and Blood Institute's Framingham Heart Study is supported by contract N01-HC-25195. The accelerometry study was supported by R01AG047645. NR 39 TC 3 Z9 3 U1 2 U2 6 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 MAR PY 2015 VL 4 IS 3 AR e001379 DI 10.1161/JAHA.114.001379 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0TV UT WOS:000351520300014 PM 25736442 ER PT J AU Singer, DE Hellkamp, AS Yuan, Z Lokhnygina, Y Patel, MR Piccini, JP Hankey, GJ Breithardt, G Halperin, JL Becker, RC Hacke, W Nessel, CC Mahaffey, KW Fox, KAA Califf, RM AF Singer, Daniel E. Hellkamp, Anne S. Yuan, Zhong Lokhnygina, Yuliya Patel, Manesh R. Piccini, Jonathan P. Hankey, Graeme J. Breithardt, Guenter Halperin, Jonathan L. Becker, Richard C. Hacke, Werner Nessel, Christopher C. Mahaffey, Kenneth W. Fox, Keith A. A. Califf, Robert M. CA ROCKET AF Investigators TI Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE anticoagulants; arrhythmia; embolism; prevention; risk factors ID NONVALVULAR ATRIAL-FIBRILLATION; NORMALIZED RATIO CONTROL; STROKE PREVENTION; ORAL ANTICOAGULANT; INTENSITY; RIVAROXABAN; QUALITY AB Background-In the ROCKET AF (Rivaroxaban-Once-daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter-INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow-up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results-We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change-based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in-range INRs ("corrections") versus INRs that were out of range in the opposite direction ("overshoots"). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change-based approach, depending on assumptions. However, large inter-regional differences in anticoagulation control persisted. Conclusions-TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow-up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change-based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter-regional differences previously reported. C1 [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Yuan, Zhong; Nessel, Christopher C.] Janssen Res & Dev, Raritan, NJ USA. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia. [Breithardt, Guenter] Univ Hosp Munster, Dept Cardiovasc Med, Div Electrophysiol, Munster, Germany. [Becker, Richard C.] Univ Cincinnati, Coll Med, Dept Internal Med, Cincinnati, OH USA. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA. RP Singer, DE (reprint author), Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, S50-9, Boston, MA 02114 USA. EM dsinger@partners.org RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Janssen Research & Development, (Raritan, NJ, USA); Bayer HealthCare AG (Leverkusen, Germany); Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital FX The ROCKET AF trial was supported by research grants from Janssen Research & Development, (Raritan, NJ, USA) and Bayer HealthCare AG (Leverkusen, Germany). Dr Singer was supported by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital. NR 22 TC 3 Z9 3 U1 0 U2 3 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 MAR PY 2015 VL 4 IS 3 AR e001349 DI 10.1161/JAHA.114.001349 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0TV UT WOS:000351520300006 PM 25736441 ER PT J AU Sugiyama, T Hasegawa, K Kobayashi, Y Takahashi, O Fukui, T Tsugawa, Y AF Sugiyama, Takehiro Hasegawa, Kohei Kobayashi, Yasuki Takahashi, Osamu Fukui, Tsuguya Tsugawa, Yusuke TI Differential Time Trends of Outcomes and Costs of Care for Acute Myocardial Infarction Hospitalizations by ST Elevation and Type of Intervention in the United States, 2001-2011 SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute myocardial infarction; hospital costs; in-hospital mortality; time trend ID HEART-DISEASE; CASE-FATALITY; MORTALITY; NSTEMI AB Background-Little is known whether time trends of in-hospital mortality and costs of care for acute myocardial infarction (AMI) differ by type of AMI (ST-elevation myocardial infarction [STEMI] vs. non-ST-elevation [NSTEMI]) and by the intervention received (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], or no intervention) in the United States. Methods and Results-We conducted a serial cross-sectional study of all hospitalizations for AMI aged 30 years or older using the Nationwide Inpatient Sample, 2001-2011 (1 456 154 discharges; a weighted estimate of 7 135 592 discharges). Hospitalizations were stratified by type of AMI and intervention, and the time trends of in-hospital mortality and hospital costs were examined for each combination of the AMI type and intervention, after adjusting for both patient-and hospital-level characteristics. Compared with 2001, adjusted in-hospital mortality improved significantly for NSTEMI patients in 2011, regardless of the intervention received (PCI odds ratio [OR] 0.68, 95% CI 0.56 to 0.83; CABG OR 0.57, 0.45 to 0.72; without intervention OR 0.61, 0.57 to 0.65). As for STEMI, a decline in adjusted in-hospital mortality was significant for those who underwent PCI (OR 0.83; 0.73 to 0.94); however, no significant improvement was observed for those who received CABG or without intervention. Hospital costs per hospitalization increased significantly for patients who underwent intervention, but not for those without intervention. Conclusions-In the United States, the decrease in in-hospital mortality and the increase in costs differed by the AMI type and the intervention received. These non-uniform trends may be informative for designing effective health policies to reduce the health and economic burdens of AMI. C1 [Sugiyama, Takehiro] Natl Ctr Global Hlth & Med, Ctr Clin Sci, Dept Clin Study & Informat, Tokyo 1628655, Japan. [Sugiyama, Takehiro; Kobayashi, Yasuki] Univ Tokyo, Grad Sch Med, Dept Publ Hlth Hlth Policy, Tokyo, Japan. [Hasegawa, Kohei] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Takahashi, Osamu; Fukui, Tsuguya] St Lukes Int Univ, Ctr Clin Epidemiol, Tokyo, Japan. [Tsugawa, Yusuke] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA USA. [Tsugawa, Yusuke] Harvard Univ, Sch Med, Boston, MA USA. [Tsugawa, Yusuke] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. RP Sugiyama, T (reprint author), Natl Ctr Global Hlth & Med, Ctr Clin Sci, Dept Clin Study & Informat, 1-21-1 Toyama, Tokyo 1628655, Japan. EM tsugiyama-tky@umin.ac.jp FU St. Luke's Life Science Institute, Tokyo, Japan; Harvard University; Honjo International Scholarship Foundation FX This study was supported by St. Luke's Life Science Institute, Tokyo, Japan. Dr Tsugawa is funded by Harvard University and Honjo International Scholarship Foundation. NR 29 TC 6 Z9 6 U1 1 U2 3 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 MAR PY 2015 VL 4 IS 3 AR e001445 DI 10.1161/JAHA.114.001445 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0TV UT WOS:000351520300021 PM 25801759 ER PT J AU Wheeler, JB Mukherjee, R Stroud, RE Jones, JA Ikonomidis, JS AF Wheeler, Jason B. Mukherjee, Rupak Stroud, Robert E. Jones, Jeffrey A. Ikonomidis, John S. TI Relation of Murine Thoracic Aortic Structural and Cellular Changes With Aging to Passive and Active Mechanical Properties SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE aging; aorta; compliance; contractility ID AGE-RELATED-CHANGES; INTIMA-MEDIA THICKNESS; ARTERIAL STIFFNESS; COMPUTED-TOMOGRAPHY; RAT AORTA; DIAMETER; ANEURYSM; COLLAGEN; GENDER; MATRIX AB Background-Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these agerelated changes in altering aortic mechanical function are not well understood. Methods and Results-Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age. Conclusions-These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies. C1 [Wheeler, Jason B.; Mukherjee, Rupak; Stroud, Robert E.; Jones, Jeffrey A.; Ikonomidis, John S.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Jones, Jeffrey A.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Jones, JA (reprint author), Med Univ S Carolina, Cardiothorac Surg Res, Strom Thurmond Res Bldg,114 Doughty St,Suite 338, Charleston, SC 29425 USA. EM jonesja@musc.edu FU NIH National Institute on Aging [R01 AG036854]; VA BLRD Merit Award [2I01 BX000904-04]; [T32 HL007260-37] FX This study was supported by NIH National Institute on Aging Grant R01 AG036854 (J.S.I.), VA BLR&D Merit Award 2I01 BX000904-04 (J.A.J.), and by T32 HL007260-37 (J.B.W.). NR 49 TC 3 Z9 3 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 MAR PY 2015 VL 4 IS 3 AR e001744 DI 10.1161/JAHA.114.001744 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0TV UT WOS:000351520300028 PM 25716945 ER PT J AU Bishnoi, RJ Baig, MR Brown, FW AF Bishnoi, Ram Jeevan Baig, Muhammad Rais Brown, Frederick William TI A case of nicotine withdrawal delirium SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION LA English DT Editorial Material DE Delirium; Nicotine; Withdrawals AB Nicotine withdrawal is not a well recognized cause of delirium. A few published cases are on post-operative, terminally ill cancer or neuro-intensive care unit patients. Because of the high incidence of morbidity and mortality of delirium it is important to identify and treat delirium promptly and effectively. We report a case of delirium after sudden cessation of smoking in a heavy smoker, with schizophrenia, hospitalized for stabilization of psychiatric illness. C1 [Bishnoi, Ram Jeevan] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Baig, Muhammad Rais; Brown, Frederick William] Audie L Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Baig, MR (reprint author), Audie L Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM muhammad.baig@va.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU PAKISTAN MEDICAL ASSOC PI KARACHI PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN SN 0030-9982 J9 J PAK MED ASSOC JI J. Pak. Med. Assoc. PD MAR PY 2015 VL 65 IS 3 BP 320 EP 321 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CD9NI UT WOS:000351424600022 PM 25933572 ER PT J AU Jordan, WD Rovin, J Moainie, S Bavaria, J Cambria, R Fillinger, M McMillan, W Matsumura, JS AF Jordan, William D. Rovin, Joshua Moainie, Sina Bavaria, Joseph Cambria, Richard Fillinger, Mark McMillan, William Matsumura, Jon S. TI Results of a prospective multicenter trial of CTAG thoracic endograft SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ENDOVASCULAR AORTIC REPAIR; SECONDARY INTERVENTIONS; EUROPEAN COLLABORATORS; ANEURYSMS; REGISTRY; EUROSTAR; RISK AB Objective: As thoracic aortic aneurysms (TAAs) are more frequently being treated with endografts, the anatomic challenges of the thoracic aorta have led to design modifications of endografts. The Conformable GORE TAG (CTAG) device (W. L. Gore & Associates, Flagstaff, Ariz) was specifically designed to be more conformable in tortuous anatomy, more resistant to compression, and more accommodating to various aortic diameters compared with the original GORE TAG device. This prospective, multicenter study evaluated the safety and effectiveness of the CTAG endograft in the repair of descending TAA. Methods: This was a prospective, multicenter regulatory study with a primary end point of freedom from major device event through 1 month after treatment. Two-year outcomes included aneurysm-related morbidity (endoleaks and morphology changes), aneurysm-related mortality, and all-cause mortality. Results: Fifty-one patients were enrolled between October 2009 and October 2010, with at least one endograft implanted in 50 patients. After the regulatory study successfully completed its primary end point and expanded to a continued-access phase, 15 additional patients were enrolled in the continued-access arm of the study from February 2011 until September 2011, for a total treatment group of 66 patients for the early results and 65 patients for the long-term clinical results with imaging evaluation. There was one 30-day death (1.5%), two patients (3%) with spinal cord ischemia, and two central strokes (3%) <= 30 days. Five patients (7.6%) died <= 1 year; 1 of ascending aortic aneurysm rupture, 2 of cardiac disease, and 2 of respiratory failure. The core laboratory adjudicated 1-month imaging in 60 patients (92.3%), where nine endoleaks (15.0%) were identified (1 type Ia, 4 type II, and 4 indeterminate). Forty-five patients (69.2%) had 2-year imaging with five endoleaks (11.1%; two type II and three indeterminate), and one patient had a distal aortic dilatation that required a secondary intervention. At 2 years, 20 of 38 imaged patients (52.6%) had aneurysm shrinkage >= 5 mm, 15(39.5%) had no change in diameter, and three patients (7.9%) had an increase in aneurysm diameter of >= 5 mm. There were no conversions, fractures, compressions, or aneurysm ruptures of the treated segment through 2 years. Conclusions: This next-generation thoracic endograft has a low rate of major device events through 2 years, with no graft compressions or device failures. The data for this new endograft demonstrate favorable outcomes and confirm low risks for treatment for patients with TAA. Follow-up will be continued for 5 years. C1 [Jordan, William D.] Univ Alabama Birmingham, Dept Surg, Div Vasc Surg & Endovasc Therapy, Birmingham, AL 35294 USA. [Rovin, Joshua] Cardiac Surg Associates, Clearwater, FL USA. [Moainie, Sina] CorVasc MDs PC, Indianapolis, IN USA. [Bavaria, Joseph] Univ Penn, Dept Surg, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Cambria, Richard] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Fillinger, Mark] Dartmouth Hitchcock Med Ctr, Dept Surg, Div Vasc Surg, Lebanon, NH 03766 USA. [McMillan, William] North Mem Hlth Care Minneapolis, Robbinsdale, MN USA. [Matsumura, Jon S.] Univ Wisconsin, Dept Surg, Div Vasc Surg, Madison, WI USA. RP Jordan, WD (reprint author), Univ Alabama Birmingham, 1808 7th Ave S,BDB 503, Birmingham, AL 35294 USA. EM wdjordan@uab.edu FU W. L. Gore Associates [06-02, 08-01, 08-03, GRT 10-11, IBE 12-04]; Medtronic Inc [Endurant AUI 089, Valor II IP 078, Rescue IP 117]; Aptus Endosystems Inc [Aptus ANCHOR Registry CD03469, Aptus Staple 2 2006-01]; Endologix [Ventana CP-0004, Endologix 34]; Lombard Medical Technologies [Pythagoras 2008-1]; Trivascular Inc [Trivascular Ovation 771-0006]; Cordis Corporation [Cordis Inspiration P114601]; Medtronic Technologies; Aptus Endosystems Inc.; Medtronic Vascular (Medtronic Dissection); Cook; Abbott [ACT1]; Covidien (Covidien NPI); Endologix (PEVAR); NIH [R01AG037120]; Medtronic; Ethicon; Edwards; Sorin; Endologix FX W.D.J. has the following disclosures: research grants received from W. L. Gore & Associates (Gore 06-02; Gore 08-01; Gore 08-03; Gore GREAT Registry GRT 10-11; Gore IBE 12-04), Medtronic Inc (Endurant AUI 089; Valor II IP 078; Rescue IP 117), Aptus Endosystems Inc (Aptus ANCHOR Registry CD03469; Aptus Staple 2 2006-01), Endologix (Ventana CP-0004; Endologix 34), Lombard Medical Technologies (Pythagoras 2008-1), Trivascular Inc (Trivascular Ovation 771-0006), and Cordis Corporation (Cordis Inspiration P114601); consulting fees received from W. L. Gore & Associates, Medtronic Technologies, Endologix, Lombard Medical Technologies, and Aptus Endosystems Inc. J. B. has the following disclosures: research grants received from W. L. Gore & Associates (Gore 08-01, Gore 08-02, Gore 08-03, Gore 11-02), Medtronic Vascular (Medtronic Dissection), and Cook (Cook TX2 Post Market; Cook Zenith Dissection; Cook Transfix TX2 LP Blunt Trauma). J. S. M. has the following disclosures: research grants received from Abbott (ACT1), Cook (Cook NPI), Covidien (Covidien NPI), Endologix (PEVAR), W. L. Gore & Associates (Gore TAG 0803), and NIH (R01AG037120). S. M. has the following disclosures: research grants from W. L. Gore & Associates (Gore 08-03), Medtronic, Ethicon, Edwards, and Sorin. J. R. has the following disclosures: research grants received from W. L. Gore & Associates (Gore 08-03); consulting fees from W. L. Gore & Associates. M. F. has the following disclosures: research grant from W. L. Gore & Associates (Gore 08-03); consulting fees received from W. L. Gore & Associates, Endologix, and Cook. W. M. and R. C. have each received research grants from W. L. Gore & Associates (Gore 08-03). NR 14 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAR PY 2015 VL 61 IS 3 BP 589 EP 595 DI 10.1016/j.jvs.2014.09.033 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CC3BZ UT WOS:000350220700001 PM 25720923 ER PT J AU Graham, DY AF Graham, David Y. TI Roadmap for elimination of gastric cancer in Korea SO KOREAN JOURNAL OF INTERNAL MEDICINE LA English DT Review ID HELICOBACTER-PYLORI-INFECTION; ERADICATION THERAPY; TRIPLE THERAPY; 1ST-LINE; JAPAN; SURVEILLANCE; TRENDS; TIME; RISK AB Most gastric cancers are caused by infection with the common human bacterial pathogen, Helicobacter pylori. It is now accepted that gastric cancer can be prevented and virtually eliminated by H. pylori eradication and this knowledge was responsible for country-wide H. pylori eradication combined with secondary cancer prevention for those with residual risk that was introduced in Japan in 2013. Korea is a high H. pylori prevalence and high gastric cancer incidence country and a good candidate for a gastric cancer elimination program. The presence of an H. pylori infection is now considered as an indication for treatment of the infection. However, antimicrobial drug resistance is common among H. pylori in Korea making effective therapy problematic. Country-wide studies of the local and regional antimicrobial resistance patterns are needed to choose the most appropriate therapies. H. pylori and gastric cancer eradication can be both efficient and cost effective making it possible and practical to make Korea H. pylori and gastric cancer free. There is no reason to delay. C1 Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Graham, DY (reprint author), Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.edu FU Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service [DK067366, DK56338] FX The author thanks Dr. Sun-Young Lee for reading the draft manuscript and making important suggestions. Dr. Graham is supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service grants DK067366 and DK56338 which funds the Texas Medical Center Digestive Diseases Center. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the VA or NIH. NR 32 TC 3 Z9 3 U1 0 U2 3 PU KOREAN ASSOC INTERNAL MEDICINE PI SEOUL PA 101-2501 LOTTE CASTLE PRESIDENT, 109 MAPO-DAERO, MAPO-GU, SEOUL, 121-916, SOUTH KOREA SN 1226-3303 J9 KOREAN J INTERN MED JI Korean J. Intern. Med. PD MAR PY 2015 VL 30 IS 2 BP 133 EP 139 DI 10.3904/kjim.2015.30.2.133 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CD9LL UT WOS:000351419700001 PM 25750552 ER PT J AU Kim, KW Shinagare, AB Krajewski, KM Pyo, J Tirumani, SH Jagannathan, JP Ramaiya, NH AF Kim, Kyung Won Shinagare, Atul B. Krajewski, Katherine M. Pyo, Junhee Tirumani, Sree Harsha Jagannathan, Jyothi P. Ramaiya, Nikhil H. TI Fluid Retention Associated with Imatinib Treatment in Patients with Gastrointestinal Stromal Tumor: Quantitative Radiologic Assessment and Implications for Management SO KOREAN JOURNAL OF RADIOLOGY LA English DT Article DE Imatinib; Fluid retention; Subcutaneous edema; Ascites; Computed tomography ID CHRONIC MYELOID-LEUKEMIA; EORTC-ISG-AGITG; TYROSINE KINASE; SARCOMA GROUP; MESYLATE; CANCER; TRIAL; PROGRESSION; THERAPY; FAILURE AB Objective: We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. Materials and Methods: In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. Results: The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 800/0), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. Conclusion: Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management. C1 [Kim, Kyung Won; Shinagare, Atul B.; Krajewski, Katherine M.; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging,Med Sch, Boston, MA 02115 USA. [Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul 138736, South Korea. [Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, Seoul 138736, South Korea. [Pyo, Junhee] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 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 Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI14C1090] FX This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI14C1090). NR 22 TC 4 Z9 4 U1 0 U2 1 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 MAR-APR PY 2015 VL 16 IS 2 BP 304 EP 313 DI 10.3348/kjr.2015.16.2.304 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD9NK UT WOS:000351424800007 PM 25741192 ER PT J AU Chan, AHY Stewart, AW Harrison, J Camargo, CA Black, PN Mitchell, EA AF Chan, Amy H. Y. Stewart, Alistair W. Harrison, Jeff Camargo, Carlos A., Jr. Black, Peter N. Mitchell, Edwin A. TI The effect of an electronic monitoring device with audiovisual reminder function on adherence to inhaled corticosteroids and school attendance in children with asthma: a randomised controlled trial SO LANCET RESPIRATORY MEDICINE LA English DT Article ID INNER-CITY CHILDREN; HEALTH-CARE COSTS; CHILDHOOD ASTHMA; PATIENT ADHERENCE; IMPROVE ADHERENCE; CLINICAL-TRIAL; MEDICATION; EXACERBATIONS; PREVALENCE; OUTCOMES AB Background Suboptimum adherence to preventive asthma treatment is associated with substantial morbidity and mortality, yet adherence often remains poor. We aimed to investigate whether use of an inhaler with audiovisual reminders leads to improved adherence and asthma outcomes in school-aged children who presented to the emergency department with an asthma exacerbation. Methods We did a randomised controlled trial in patients aged 6-15 years who attended the regional emergency department in Auddand, New Zealand with an asthma exacerbation and were on regular inhaled corticosteroids. Using a simple, unrestricted block randomisation with block sizes of 200, we randomly assigned patients to receive an electronic monitoring device for use with their preventer inhaler with the audiovisual reminder functions either enabled to support adherence to inhaled corticosteroids (intervention group) or disabled (control group). Participants were followed up every 2 months for 6 months. The primary outcomes were adherence to preventive inhaled corticosteroids and number of days absent from school for any reason. Asthma control was assessed as a secondary outcome. All analyses were done in the intention-to-treat population. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613001353785. Findings The study took place between May 10,2010, and Feb 26,2012. We randomly assigned 220 patients, 110 to the intervention group and 110 to the control group. Median percentage adherence was 84% (10th percentile 54%, 90th percentile 96%) in the intervention group, compared with 30% (8%, 68%) in the control group (p<0.0001). The proportion of days absent from school for any reason was 1.9% (10th percentile 0.0%, 90th percentile 7.9%) in the intervention group and 1.7% (0.0%, 8.6%) in the control group. The change in asthma morbidity score from baseline to 6 months was significantly greater in the intervention group than in the control group (p=0.008), with a reduction of 2.0 points from a mean baseline score of 9.3 (SD 2.2) to 7.3 (2.1) in the intervention group, compared with a reduction of 1.2 points from a baseline of 9.2 (2.5) to 8.0 (2.2) in the control group. Interpretation Use of an electronic monitoring device with an audiovisual reminder led to significant improvements in adherence to inhaled corticosteroids in school-aged children with asthma. This intervention could be beneficial for the improvement of asthma control in patients for whom poor asthma control is related to poor adherence. C1 [Chan, Amy H. Y.; Harrison, Jeff] Univ Auckland, Fac Med & Hlth Sci, Sch Pharm, Auckland 1023, New Zealand. [Stewart, Alistair W.] Univ Auckland, Fac Med & Hlth Sci, Sch Populat Hlth, Epidemiol & Biostat, Auckland 1023, New Zealand. [Black, Peter N.] Univ Auckland, Fac Med & Hlth Sci, Dept Pharmacol & Clin Pharmacol, Auckland 1023, New Zealand. [Mitchell, Edwin A.] Univ Auckland, Fac Med & Hlth Sci, Sch Med, Dept Pediat Child & Youth Hlth, Auckland 1023, New Zealand. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. RP Chan, AHY (reprint author), Univ Auckland, Fac Med & Hlth Sci, Sch Pharm, Auckland 1023, New Zealand. EM a.chan@auckland.ac.nz OI Harrison, Jeff/0000-0001-8478-7469 FU Health Research Council of New Zealand (a government funding organisation); Cure Kids (a charitable organisation that funds child health research) FX This study was funded by the Health Research Council of New Zealand (a government funding organisation) and Cure Kids (a charitable organisation that funds child health research). Electronic monitoring devices were provided by Nexus 6 (Auckland, New Zealand). Investigators provided feedback to the manufacturer about device functions, but the manufacturer had no involvement in any part of the study. We thank Maye Hamed, Elizabeth Garrett, and Sherron Kneebone, who were involved in data collection; staff at the Auckland and Waitemata district health board emergency departments for assistance with organisation of the trial; and the study participants and their families for their involvement in the study. NR 60 TC 17 Z9 17 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD MAR PY 2015 VL 3 IS 3 BP 210 EP 219 DI 10.1016/S2213-2600(15)00008-9 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CE0FN UT WOS:000351480000017 PM 25617215 ER PT J AU Odejide, OO Cronin, AM Davidoff, AJ LaCasce, AS Abel, GA AF Odejide, Oreofe O. Cronin, Angel M. Davidoff, Amy J. LaCasce, Ann S. Abel, Gregory A. TI Limited stage diffuse large B-cell lymphoma: comparative eff ectiveness of treatment strategies in a large cohort of elderly patients SO LEUKEMIA & LYMPHOMA LA English DT Article DE Diff use large B-cell lymphoma; rituximab; comparative eff ectiveness; elderly ID NON-HODGKINS-LYMPHOMA; LOCALIZED AGGRESSIVE LYMPHOMA; CHEMOTHERAPY PLUS RITUXIMAB; DETUDE-DES-LYMPHOMES; COMORBIDITY INDEX; CHOP CHEMOTHERAPY; BRITISH-COLUMBIA; ONCOLOGY-GROUP; RADIOTHERAPY; OUTCOMES AB Optimal treatment for limited stage diffuse large B-cell lymphoma (DLBCL) in the elderly is controversial. Using the Surveillance, Epidemiology and End Results-Medicare database, we compared overall survival (OS), time to second-line therapy (surrogate for recurrence) and adverse events in elderly patients diagnosed with stage I or II DLBCL in 1999-2009, who received either abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) plus radiation or 6-8 cycles of RCHOP alone. Of 874 patients, 359 received abbreviated RCHOP with radiation, and 515 received a full course of RCHOP. In propensity score-adjusted analyses, OS was similar in both groups (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.76, 1.38). Abbreviated RCHOP with radiation was associated with lower risk of second-line therapy (HR 0.71, 95% CI 0.53, 0.94) and lower odds of febrile neutropenia (odds ratio [OR] 0.27, 95% CI 0.15, 0.50). While the two treatments resulted in similar survival, our data suggest that abbreviated RCHOP with radiation may be better tolerated than a full course of RCHOP. C1 [Odejide, Oreofe O.; Cronin, Angel M.; Abel, Gregory A.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02215 USA. [Odejide, Oreofe O.; LaCasce, Ann S.] Dana Farber Canc Inst, Ctr Lymphoma, Boston, MA 02215 USA. [Abel, Gregory A.] Dana Farber Canc Inst, Ctr Leukemia, Dept Med Oncol, Boston, MA 02215 USA. [Davidoff, Amy J.] Agcy Healthcare Res & Qual, Rockville, MD USA. RP Abel, GA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Gregory_abel@dfci.harvard.edu FU American Society of Hematology Clinical Research Training Institute; Lymphoma Research Foundation Postdoctoral Fellow Award FX The authors thank Philippe Armand for assistance with access to the DF/Lymphoma CRIS database. This research was supported by the American Society of Hematology Clinical Research Training Institute (O.O.O) and a Lymphoma Research Foundation Postdoctoral Fellow Award (O.O.O). NR 33 TC 11 Z9 11 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAR PY 2015 VL 56 IS 3 BP 716 EP 724 DI 10.3109/10428194.2014.930853 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CD5RC UT WOS:000351144500027 PM 24913508 ER PT J AU Carlson, C Merel, SE Yukawa, M AF Carlson, Charlotte Merel, Susan E. Yukawa, Michi TI Geriatric Syndromes and Geriatric Assessment for the Generalist SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Geriatric syndromes; Geriatric assessment; Frailty; Care delivery systems; Primary care ID RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; OLDER-ADULTS; URINARY-INCONTINENCE; CARE MANAGEMENT; TRANSITIONAL CARE; CLINICAL-PRACTICE; ELDERLY-PATIENTS; TASK-FORCE; TAI CHI AB Geriatric assessment is an increasingly important area of outpatient medicine, given the unprecedented aging of the US population. Screening and evaluation for geriatric syndromes, particularly falls, urinary incontinence, frailty, and cognitive impairment, are crucial aspects of outpatient geriatric assessment. Innovative models of care are emerging to improve quality of care and enhance cost savings for the geriatric patient. High-value features of geriatric care systems include providing increased 24/7 access to care, a multidisciplinary team-based approach to care, performing medication reconciliation and comprehensive geriatric assessments, and integrating palliative care into treatment planning. C1 [Carlson, Charlotte] Inst Aging, On Lok Senior Hlth, San Francisco, CA 94118 USA. [Merel, Susan E.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Yukawa, Michi] San Francisco VA Med Ctr, San Francisco, CA 93121 USA. RP Carlson, C (reprint author), Inst Aging, On Lok Senior Hlth, 3575 Geary Blvd, San Francisco, CA 94118 USA. EM Charlotte.carlson@ucsf.edu NR 69 TC 8 Z9 8 U1 6 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAR PY 2015 VL 99 IS 2 BP 263 EP + DI 10.1016/j.mcna.2014.11.003 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA CD8CH UT WOS:000351322300005 PM 25700583 ER PT J AU Lum, HD Sudore, RL Bekelman, DB AF Lum, Hillary D. Sudore, Rebecca L. Bekelman, David B. TI Advance Care Planning in the Elderly SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Advance care planning; Advance directives; Surrogate decision maker; Patient-doctor relationship; Communication ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; SURROGATE DECISION-MAKING; SUSTAINING TREATMENT; TREATMENT PREFERENCES; NURSING FACILITIES; PHYSICIAN ORDERS; OLDER-ADULTS; END; DIRECTIVES AB Key components of advance care planning (ACP) for the elderly include choosing a surrogate decision maker, identifying personal values, communicating with surrogates and clinicians, documenting wishes in advance directives, and translating values and preferences for future medical care into medical orders. ACP often involves multiple brief discussions over time. This article outlines common benefits and barriers to ACP in primary care, and provides practical approaches to integrating key ACP components into primary care for older adults. Opportunities for multidisciplinary teams to incorporate ACP into brief clinic visits are highlighted. C1 [Lum, Hillary D.] Univ Colorado, Sch Med, Dept Med, Div Geriatr Med, Aurora, CO 80045 USA. [Lum, Hillary D.] VA Eastern Colorado Healthcare Syst, Dept Med, Denver, CO 80220 USA. [Sudore, Rebecca L.] Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Bekelman, David B.] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Aurora, CO 80045 USA. [Bekelman, David B.] VA Eastern Colorado Healthcare Syst, Dept Med, Denver, CO 80220 USA. RP Lum, HD (reprint author), Univ Colorado, Sch Med, Dept Med, Div Geriatr Med, 12631 East 17th Ave,B-179, Aurora, CO 80045 USA. EM Hillary.Lum@ucdenver.edu NR 48 TC 6 Z9 7 U1 9 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAR PY 2015 VL 99 IS 2 BP 391 EP + DI 10.1016/j.mcna.2014.11.010 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA CD8CH UT WOS:000351322300012 PM 25700590 ER PT J AU Rodriguez, JC Dzierzewski, JM Alessi, CA AF Carlos Rodriguez, Juan Dzierzewski, Joseph M. Alessi, Cathy A. TI Sleep Problems in the Elderly SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Sleep problems; Sleep apnea; Insomnia; Older adults; Diagnosis and treatment ID RANDOMIZED CONTROLLED-TRIAL; OLDER-ADULTS; INSOMNIA; APNEA; COMPLAINTS; PRESSURE AB Epidemiologic studies have shown that approximately 50% of older adults have sleep problems, many of which carry deleterious consequences that affect physical and mental health and also social functioning. However, sleep problems in late life are often unrecognized, and are inadequately treated in clinical practice. This article focuses on the diagnosis and treatment of the 2 most common sleep problems in older patients: sleep apnea and insomnia. C1 [Carlos Rodriguez, Juan; Dzierzewski, Joseph M.; Alessi, Cathy A.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA 91343 USA. [Carlos Rodriguez, Juan; Dzierzewski, Joseph M.; Alessi, Cathy A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Carlos Rodriguez, Juan] Pontificia Univ Catolica Chile, Dept Med, Santiago, Chile. RP Rodriguez, JC (reprint author), VA Greater Los Angeles Healthcare Syst, 16111 Plummer St 11E, North Hills, CA 91343 USA. EM juan.rodrigueztapia@va.gov FU UCLA Claude D. Pepper Older Americans Independence Center [NIA 5P30 AG028748]; NIH/NCATS UCLA CM [UL1TR000124]; VA Advanced Geriatrics Fellowship Program; Geriatric Research, Education, and Clinical Center (GRECC); VA Greater Los Angeles Healthcare System FX This work was supported by UCLA Claude D. Pepper Older Americans Independence Center (NIA 5P30 AG028748); NIH/NCATS UCLA CM (UL1TR000124); the VA Advanced Geriatrics Fellowship Program; the Geriatric Research, Education, and Clinical Center (GRECC); and the VA Greater Los Angeles Healthcare System. NR 19 TC 8 Z9 11 U1 3 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAR PY 2015 VL 99 IS 2 BP 431 EP + DI 10.1016/j.mcna.2014.11.013 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CD8CH UT WOS:000351322300015 PM 25700593 ER PT J AU Alam, M Ahmad, R Rajabi, H Kufe, D AF Alam, Maroof Ahmad, Rehan Rajabi, Hasan Kufe, Donald TI MUC1-C Induces the LIN28B -> LET-7 -> HMGA2 Axis to Regulate Self-Renewal in NSCLC SO MOLECULAR CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; EMBRYONIC STEM-CELLS; LUNG-CANCER; TRANSCRIPTION FACTOR; MICRORNA BIOGENESIS; LET-7 MICRORNAS; ONCOPROTEIN; HMGA2; EXPRESSION AB The LIN28B -> let-7 pathway contributes to regulation of the epithelial-mesenchymal transition (EMT) and stem cell self-renewal. The oncogenic MUC1-C transmembrane protein is aberrantly overexpressed in lung and other carcinomas; however, there is no known association between MUC1-C and the LIN28B -> let-7 pathway. Here in non-small cell lung cancer (NSCLC), silencing MUC1-C downregulates the RNA-binding protein LIN28B and coordinately increases the miRNA let-7. Targeting MUC1-C function with a dominant-negative mutant or a peptide inhibitor provided confirming evidence that MUC1-C induces LIN28B -> let-7 signaling. Mechanistically, MUC1-C promotes NF-kappa B p65 chromatin occupancy of the LIN28B first intron and activates LIN28B transcription, which is associated with suppression of let-7. Consistent with let-7-mediated inhibition of HMGA2 transcripts, targeting of MUC1-C also decreases HMGA2 expression. HMGA2 has been linked to stemness, and functions as a competing endogenous RNA (ceRNA) of let-7-mediated regulation of the TGF beta coreceptor TGFBR3. Accordingly, targeting MUC1-C suppresses HMGA2 mRNA and protein, which is associated with decreases in TGFBR3, reversal of the EMT phenotype, and inhibition of self-renewal capacity. These findings support a model in which MUC1-C activates the double up arrow LIN28B ->double down arrow let-7 ->double up arrow HMGA2 axis in NSCLC and thereby promotes EMT traits and stemness. Implications: A novel pathway is defined in which MUC1-C drives LIN28B -> let-7 -> HMGA2 signaling, EMT, and self-renewal in NSCLC. (C) 2014 AACR. C1 [Alam, Maroof; Ahmad, Rehan; Rajabi, Hasan; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,Dana 830, Boston, MA 02215 USA. EM donald_kufe@dfci.harvard.edu FU NCI of the NIH [CA166480, CA97098] FX This work was supported by the NCI of the NIH under award numbers CA166480 and CA97098. NR 52 TC 11 Z9 12 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAR PY 2015 VL 13 IS 3 BP 449 EP 460 DI 10.1158/1541-7786.MCR-14-0363 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CD6UA UT WOS:000351223800006 PM 25368430 ER PT J AU Luo, LY Kim, E Cheung, HW Weir, BA Dunn, GP Shen, RR Hahn, WC AF Luo, Leo Y. Kim, Eejung Cheung, Hiu Wing Weir, Barbara A. Dunn, Gavin P. Shen, Rhine R. Hahn, William C. TI The Tyrosine Kinase Adaptor Protein FRS2 Is Oncogenic and Amplified in High-Grade Serous Ovarian Cancer SO MOLECULAR CANCER RESEARCH LA English DT Article ID CELL-LINES; SIGNAL-TRANSDUCTION; FALLOPIAN-TUBE; GROWTH; AMPLIFICATION; GENES; CARCINOGENESIS; IDENTIFICATION; INTERROGATION; LIPOSARCOMA AB High-grade serous ovarian cancers (HGSOC) are characterized by widespread recurrent regions of copy-number gain and loss. Here, we interrogated 50 genes that are recurrently amplified in HGSOC and essential for cancer proliferation and survival in ovarian cancer cell lines. FRS2 is one of the 50 genes located on chromosomal region 12q15 that is focally amplified in 12.5% of HGSOC. We found that FRS2-amplified cancer cell lines are dependent on FRS2 expression, and that FRS2 overexpression in immortalized human cell lines conferred the ability to grow in an anchorage-independent manner and as tumors in immunodeficient mice. FRS2, an adaptor protein in the FGFR pathway, induces downstream activation of the Ras-MAPK pathway. These observations identify FRS2 as an oncogene in a subset of HGSOC that harbor FRS2 amplifications. C1 [Luo, Leo Y.] Harvard Univ, Sch Med, Hlth Sci & Technol Program, Boston, MA 02115 USA. [Luo, Leo Y.; Kim, Eejung; Cheung, Hiu Wing; Weir, Barbara A.; Dunn, Gavin P.; Hahn, William C.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Luo, Leo Y.; Kim, Eejung; Shen, Rhine R.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cheung, Hiu Wing] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC USA. [Dunn, Gavin P.] Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO USA. [Shen, Rhine R.] Astellas Pharma US Inc, Santa Monica, CA USA. [Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Brigham & Womens Hosp, Med Oncol, Dana 1538,450 Brookline Ave, Boston, MA 02215 USA. EM William_Hahn@dfci.harvard.edu FU U.S. NIH [U01 CA176058]; Starr Foundation [I5-A533]; H.L. Snyder Medical Research Foundation FX This work was supported in part by grants from the U.S. NIH (U01 CA176058), the Starr Foundation (I5-A533), and the H.L. Snyder Medical Research Foundation. NR 39 TC 7 Z9 7 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAR PY 2015 VL 13 IS 3 BP 502 EP 509 DI 10.1158/1541-7786.MCR-14-0407 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CD6UA UT WOS:000351223800011 PM 25368431 ER PT J AU Falk, MJ Shen, LS Gonzalez, M Leipzig, J Lott, MT Stassen, APM Diroma, MA Navarro-Gomez, D Yeske, P Bai, RK Boles, RG Brilhante, V Ralph, D DaRe, JT Shelton, R Terry, SF Zhang, Z Copeland, WC van Oven, M Prokisch, H Wallace, DC Attimonelli, M Krotoski, D Zuchner, S Gai, XW AF Falk, Marni J. Shen, Lishuang Gonzalez, Michael Leipzig, Jeremy Lott, Marie T. Stassen, Alphons P. M. Diroma, Maria Angela Navarro-Gomez, Daniel Yeske, Philip Bai, Renkui Boles, Richard G. Brilhante, Virginia Ralph, David DaRe, Jeana T. Shelton, Robert Terry, Sharon F. Zhang, Zhe Copeland, William C. van Oven, Mannis Prokisch, Holger Wallace, Douglas C. Attimonelli, Marcella Krotoski, Danuta Zuchner, Stephan Gai, Xiaowu CA MSeqDR Consortium TI Mitochondrial Disease Sequence Data Resource (MSeqDR): A global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Mitochondrial disease; Genomics; Exome; Data sharing ID HUMAN PHENOTYPE ONTOLOGY; PRIORITIZATION; COMPILATION; DISORDERS AB Success rates for genomic analyses of highly heterogeneous disorders can be greatly improved if a large cohort of patient data is assembled to enhance collective capabilities for accurate sequence variant annotation, analysis, and interpretation. Indeed, molecular diagnostics requires the establishment of robust data resources to enable data sharing that informs accurate understanding of genes, variants, and phenotypes. The "Mitochondrial Disease Sequence Data Resource (MSeqDR) Consortium" is a grass-roots effort facilitated by the United Mitochondria] Disease Foundation to identify and prioritize specific genomic data analysis needs of the global mitochondrial disease clinical and research community. A central Web portal (https://mseqdr.org) facilitates the coherent compilation, organization, annotation, and analysis of sequence data from both nuclear and mitochondrial genomes of individuals and families with suspected mitochondria! disease. This Web portal provides users with a flexible and expandable suite of resources to enable variant-, gene-, and exome-level sequence analysis in a secure, Web-based, and user-friendly fashion. Users can also elect to share data with other MSeqDR Consortium members, or even the general public, either by custom annotation tracks or through the use of a convenient distributed annotation system (DAS) mechanism. A range of data visualization and analysis tools are provided to facilitate user interrogation and understanding of genomic, and ultimately phenotypic, data of relevance to mitochondrial biology and disease. Currently available tools for nuclear and mitochondrial gene analyses include an MSeqDR GBrowse instance that hosts optimized mitochondrial disease and mitochondrial DNA (mtDNA) specific annotation tracks, as well as an MSeqDR locus-specific database (LSDB) that curates variant data on more than 1300 genes that have been implicated in mitochondrial disease and/or encode mitochondria-localized proteins. MSeqDR is integrated with a diverse array of mtDNA data analysis tools that are both freestanding and incorporated into an online exome-level dataset curation and analysis resource (GEM.app) that is being optimized to support needs of the MSeqDR community. In addition, MSeqDR supports mitochondrial disease phenotyping and ontology tools, and provides variant pathogenicity assessment features that enable community review, feedback, and integration with the public ClinVar variant annotation resource. A centralized Web-based informed consent process is being developed, with implementation of a Global Unique Identifier (GUID) system to integrate data deposited on a given individual from different sources. Community-based data deposition into MSeqDR has already begun. Future efforts will enhance capabilities to incorporate phenotypic data that enhance genomic data analyses. MSeqDR will fill the existing void in bioinformatics tools and centralized knowledge that are necessary to enable efficient nuclear and mtDNA genomic data interpretation by a range of shareholders across both clinical diagnostic and research settings. Ultimately, MSeqDR is focused on empowering the global mitochondrial disease community to better define and explore mitochondrial diseases. (C) 2014 Elsevier Inc. All rights reserved. C1 [Falk, Marni J.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA. [Falk, Marni J.; Wallace, Douglas C.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shen, Lishuang; Navarro-Gomez, Daniel; Gai, Xiaowu] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Gonzalez, Michael; Zuchner, Stephan] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn, Dept Human Genet, Coral Gables, FL 33124 USA. [Leipzig, Jeremy; Zhang, Zhe] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA. [Lott, Marie T.; Wallace, Douglas C.] Childrens Hosp Philadelphia, Ctr Mitochondrial & Epigen Med, Philadelphia, PA 19104 USA. [Stassen, Alphons P. M.] Maastricht Univ, Med Ctr, Dept Clin Genet, NL-6200 MD Maastricht, Netherlands. [Diroma, Maria Angela] Univ Bari, Dept Biosci Biotechnol & Biopharmaceut, Bari, Italy. [Yeske, Philip] United Mitochondrial Dis Fdn, Pittsburgh, PA USA. [Bai, Renkui] GeneDx Inc, Gaithersburg, MD USA. [Boles, Richard G.] Courtagen Life Sci, Woburn, MA USA. [Brilhante, Virginia] Univ Helsinki, Biomedicum Helsinki, Res Programs Unit, Mol Neurol, FIN-00014 Helsinki, Finland. [Ralph, David; DaRe, Jeana T.] Transgenomic Inc, New Haven, CT USA. [Terry, Sharon F.] Genet Alliance, Bethesda, MD USA. [Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [van Oven, Mannis] Univ Med Ctr Rotterdam, Erasmus MC, Dept Forens Mol Biol, Rotterdam, Netherlands. [Prokisch, Holger] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany. [Prokisch, Holger] Helmholtz Zentrum Munich, Munich, Germany. [Wallace, Douglas C.] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. [Krotoski, Danuta] NICHD, NIH, Bethesda, MD USA. RP Falk, MJ (reprint author), ARC, 1002c,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM falkm@email.chop.edu; Xiaowu_Gai@meei.harvard.edu RI Shen, Lishuang/B-3040-2013; OI Leipzig, Jeremy/0000-0001-7224-9620; van Oven, Mannis/0000-0003-0026-7998; Pujol, Aurora/0000-0002-9606-0600; Christodoulou, John/0000-0002-8431-0641; Diroma, Maria Angela/0000-0003-1427-8946 FU Medical Research Council [MR/K000608/1]; NHGRI NIH HHS [U41 HG006834, U41-HG006834]; NINDS NIH HHS [R01 NS021328, R01 NS083726, U54 NS078059, U54-NS078059] NR 21 TC 14 Z9 14 U1 1 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2015 VL 114 IS 3 BP 388 EP 396 DI 10.1016/j.ymgme.2014.11.016 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA CD6IC UT WOS:000351191800127 PM 25542617 ER PT J AU Gilman, SE Ni, MY Dunn, EC Breslau, J McLaughlin, KA Smoller, JW Perlis, RH AF Gilman, S. E. Ni, M. Y. Dunn, E. C. Breslau, J. McLaughlin, K. A. Smoller, J. W. Perlis, R. H. TI Contributions of the social environment to first-onset and recurrent mania SO MOLECULAR PSYCHIATRY LA English DT Article ID STRESSFUL LIFE EVENTS; NATIONAL EPIDEMIOLOGIC SURVEY; BIPOLAR AFFECTIVE-DISORDER; PSYCHIATRIC DIAGNOSTIC MODULES; COMORBIDITY SURVEY REPLICATION; GENERAL-POPULATION SAMPLE; ALCOHOL-USE-DISORDER; DSM-IV-DISORDERS; III AXIS-IV; RISK-FACTORS AB In treated cohorts, individuals with bipolar disorder are more likely to report childhood adversities and recent stressors than individuals without bipolar disorder; similarly, in registry-based studies, childhood adversities are more common among individuals who later become hospitalized for bipolar disorder. Because these types of studies rely on treatment-seeking samples or hospital diagnoses, they leave unresolved the question of whether or not social experiences are involved in the etiology of bipolar disorder. We investigated the role of childhood adversities and adulthood stressors in liability for bipolar disorder using data from the National Epidemiologic Survey on Alcohol and Related Conditions (n = 33 375). We analyzed risk for initial-onset and recurrent DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) manic episodes during the study's 3-year follow-up period. Childhood physical abuse and sexual maltreatment were associated with significantly higher risks of both first-onset mania (odds ratio (OR) for abuse: 2.23; 95% confidence interval (CI) = 1.71, 2.91; OR for maltreatment: 2.10; CI = 1.55, 2.83) and recurrent mania (OR for abuse: 1.55; CI = 1.00, 2.40; OR for maltreatment: 1.60; CI = 1.00, 2.55). In addition, past-year stressors in the domains of interpersonal instability and financial hardship were associated with a significantly higher risk of incident and recurrent mania. Exposure to childhood adversity potentiated the effects of recent stressors on adult mania. Our findings demonstrate a role of social experiences in the initial onset of bipolar disorder, as well as in its prospective course, and are consistent with etiologic models of bipolar disorder that implicate deficits in developmentally established stress-response pathways. C1 [Gilman, S. E.] Harvard Univ, Dept Social & Behav Sci, Sch Publ Hlth, Boston, MA 02115 USA. [Gilman, S. E.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. [Gilman, S. E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ni, M. Y.] Univ Hong Kong, Sch Publ Hlth, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China. [Dunn, E. C.; Smoller, J. W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Dunn, E. C.; Smoller, J. W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Dunn, E. C.; Smoller, J. W.; Perlis, R. H.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Breslau, J.] RAND Corp, Pittsburgh, PA USA. [McLaughlin, K. A.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Perlis, R. H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. RP Gilman, SE (reprint author), Harvard Univ, Dept Social & Behav Sci, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM sgilman@hsph.harvard.edu RI Gilman, Stephen/E-7632-2010; OI Gilman, Stephen/0000-0002-8331-6419; Ni, Michael/0000-0002-1217-5858; McLaughlin, Katie/0000-0002-1362-2410 FU National Institutes of Health [RO1MH087544, K24MH094614] FX We sincerely appreciate the contributions of Ms Kathleen McGaffigan to data management and statistical programming. This work was supported in part by National Institutes of Health Grants RO1MH087544 (to SEG) and K24MH094614 (to JWS). NR 75 TC 16 Z9 16 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2015 VL 20 IS 3 BP 329 EP 336 DI 10.1038/mp.2014.36 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CE4CV UT WOS:000351779300006 PM 24751965 ER PT J AU Mattheisen, M Samuels, JF Wang, Y Greenberg, BD Fyer, AJ McCracken, JT Geller, DA Murphy, DL Knowles, JA Grados, MA Riddle, MA Rasmussen, SA McLaughlin, NC Nurmi, EL Askland, KD Qin, HD Cullen, BA Piacentini, J Pauls, DL Bienvenu, OJ Stewart, SE Liang, KY Goes, FS Maher, B Pulver, AE Shugart, YY Valle, D Lange, C Nestadt, G AF Mattheisen, M. Samuels, J. F. Wang, Y. Greenberg, B. D. Fyer, A. J. McCracken, J. T. Geller, D. A. Murphy, D. L. Knowles, J. A. Grados, M. A. Riddle, M. A. Rasmussen, S. A. McLaughlin, N. C. Nurmi, E. L. Askland, K. D. Qin, H-D Cullen, B. A. Piacentini, J. Pauls, D. L. Bienvenu, O. J. Stewart, S. E. Liang, K-Y Goes, F. S. Maher, B. Pulver, A. E. Shugart, Y. Y. Valle, D. Lange, C. Nestadt, G. TI Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS SO MOLECULAR PSYCHIATRY LA English DT Article ID FAMILY-BASED ASSOCIATION; TRANSPORTER GENE SLC1A1; TYROSINE PHOSPHATASES; EXCITATORY SYNAPSES; ANOREXIA-NERVOSA; PTP-SIGMA; VARIANTS; LINKAGE; LAR; BEHAVIORS AB Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family-and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P = 4.13 x 10(-7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P = 0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P = 0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P < 1 x 10(-6), experiment-wide significant), as well as OFCC1 (P = 6.29 x 10(-5)). The suggestive findings in this study await replication in larger samples. C1 [Mattheisen, M.] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark. [Mattheisen, M.] Aarhus Univ, Ctr Integrated Sequencing iSEQ, DK-8000 Aarhus C, Denmark. [Mattheisen, M.; Lange, C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Mattheisen, M.; Lange, C.] Univ Bonn, Dept Genom Math, Bonn, Germany. [Samuels, J. F.; Wang, Y.; Grados, M. A.; Riddle, M. A.; Cullen, B. A.; Bienvenu, O. J.; Goes, F. S.; Pulver, A. E.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Greenberg, B. D.; Rasmussen, S. A.; McLaughlin, N. C.; Askland, K. D.] Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI USA. [Fyer, A. J.] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA. [McCracken, J. T.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Geller, D. A.; Pauls, D. L.; Stewart, S. E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Geller, D. A.; Pauls, D. L.; Stewart, S. E.] Harvard Univ, Sch Med, Boston, MA USA. [Murphy, D. L.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. [Knowles, J. A.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Qin, H-D] NIMH, Div Intramural Res Program, Unit Stat Genom, Intramural Res Program, Bethesda, MD 20892 USA. [Stewart, S. E.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Liang, K-Y; Maher, B.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Valle, D.] Johns Hopkins Univ, Sch Med, Inst Human Genet, Baltimore, MD USA. RP Mattheisen, M (reprint author), Aarhus Univ, Dept Biomed, Wilhjelm Meyers 4, DK-8000 Aarhus C, Denmark. EM mm@hum-gen.au.dk; gnestadt@jhmi.edu RI Mattheisen, Manuel/B-4949-2012; OI Mattheisen, Manuel/0000-0002-8442-493X; Samuels, Jack/0000-0002-6715-7905; Stewart, S. Evelyn/0000-0002-0994-6383 FU NIMH [MH071507, MH079489, MH079487, MH079488, MH079494] FX The OCD Collaborative Genetics Association Study (OCGAS) is a collaborative research study and was funded by the following NIMH Grant Numbers: MH071507, MH079489, MH079487, MH079488 and MH079494. Y-YS and H-DQ were also supported by the Intramural Research Program of the NIMH. We thank the families who have participated in the study; David Houseman, PhD, Kathleen Merikangas, PhD, and Alec Wilson, PhD, for consultation; and the clinicians, study managers and clinical interviewers at the respective study sites for their efforts in participant recruitment and clinical assessments: Columbia University: Blair Simpson, MD, PhD, Julianna Stevens, BA Katie Buchholz; Johns Hopkins University: Graham Redgrave, MD, Krista Vermillion, BA, Janice Krasnow, PhD, Jana Drew, PhD, Melissa Meyers, PhD, and Margaret Schlossberg, PhD; Harvard/Massachusetts General Hospital: Elizabeth Mancuso, BA, Alyssa Faro, BA, Ashley Brown, BA, Kesley Ramsay, BA; National Institute of Mental Health (NIMH): Theresa B DeGuzman. NR 57 TC 33 Z9 33 U1 7 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2015 VL 20 IS 3 BP 337 EP 344 DI 10.1038/mp.2014.43 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CE4CV UT WOS:000351779300007 PM 24821223 ER PT J AU Durak, O de Anda, FC Singh, KK Leussis, MP Petryshen, TL Sklar, P Tsai, LH AF Durak, O. de Anda, F. C. Singh, K. K. Leussis, M. P. Petryshen, T. L. Sklar, P. Tsai, L-H TI Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of beta-catenin SO MOLECULAR PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; BIPOLAR-DISORDER; CORTICAL DEVELOPMENT; INITIAL SEGMENT; RISK VARIANT; E-CADHERIN; SCHIZOPHRENIA; CELL; ANK3; PATHWAY AB Ankyrin-G is a scaffolding protein required for the formation of the axon initial segment in neurons. Recent genome-wide association studies and whole-exome sequencing have identified ANK3, the gene coding for ankyrin-G, to be a risk gene for multiple neuropsychiatric disorders, such as bipolar disorder, schizophrenia and autism spectrum disorder. Here, we describe a novel role for ankyrin-G in neural progenitor proliferation in the developing cortex. We found that ankyrin-G regulates canonical Wnt signaling by altering the subcellular localization and availability of beta-catenin in proliferating cells. Ankyrin-G loss-of-function increases beta-catenin levels in the nucleus, thereby promoting neural progenitor proliferation. Importantly, abnormalities in proliferation can be rescued by reducing Wnt pathway signaling. Taken together, these results suggest that ankyrin-G is required for proper brain development. C1 [Durak, O.; de Anda, F. C.; Singh, K. K.; Tsai, L-H] MIT, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Leussis, M. P.; Petryshen, T. L.] Massachusetts Gen Hosp, Psychiat & Neurodevelopmental Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Leussis, M. P.; Petryshen, T. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Leussis, M. P.; Petryshen, T. L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Leussis, M. P.; Petryshen, T. L.] Broad Inst Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Leussis, M. P.; Petryshen, T. L.] MIT, Cambridge, MA 02139 USA. [Sklar, P.] Mt Sinai Sch Med, Div Psychiat Genom, Dept Psychiat, New York, NY USA. [Sklar, P.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Sklar, P.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. RP Tsai, LH (reprint author), MIT, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, 77 Mass Ave,46-4235, Cambridge, MA 02139 USA. EM lhtsai@mit.edu FU Simons Foundation (Simons Center for the Social Brain, Massachusetts Institute of Technology); NIH RO1 Grant [MH091115]; Stanley Medical Research Institute; Howard Hughes Medical Institute FX We thank Drs A Mungenast, Y Mao, A Bero and J Graff for critical reading of the manuscript. We are thankful to Y Mao, D Rei, T Soda, P Giusti and J Graff for technical help and suggestions with the project. Super8XTOPFLASH luciferase reporter construct was a kind gift from Dr Randall Moon (University of Washington). We also thank ME Taylor and AS Gomes for their help with production of Ank3 mice. OD is a Henry Singleton (1940) Fellow (Brain and Cognitive Sciences, Massachusetts Institute of Technology). FCdA was supported by a postdoctoral fellowship from the Simons Foundation (Simons Center for the Social Brain, Massachusetts Institute of Technology). This work was partially supported by an NIH RO1 Grant (MH091115) to L-HT, a grant from the Stanley Medical Research Institute to L-HT and TLP, and the Howard Hughes Medical Institute. NR 48 TC 12 Z9 13 U1 4 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2015 VL 20 IS 3 BP 388 EP 397 DI 10.1038/mp.2014.42 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CE4CV UT WOS:000351779300013 PM 24821222 ER PT J AU Fallahi-Sichani, M Moerke, NJ Niepel, M Zhang, TH Gray, NS Sorger, PK AF Fallahi-Sichani, Mohammad Moerke, Nathan J. Niepel, Mario Zhang, Tinghu Gray, Nathanael S. Sorger, Peter K. TI Systematic analysis of BRAF(V600E) melanomas reveals a role for JNK/c-Jun pathway in adaptive resistance to drug-induced apoptosis SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE adaptive responses; BRAF(V600E) melanomas; cell-to-cell variability; RAF and MEK inhibitors; submaximal drug effect ID RAF INHIBITOR RESISTANCE; BRAF-MUTANT MELANOMA; SIGNALING NETWORKS; ACQUIRED-RESISTANCE; C-JUN; MEK INHIBITION; CELL-CYCLE; V600E MUTATION; BREAST-CANCER; S6 KINASE AB Drugs that inhibit RAF/MEK signaling, such as vemurafenib, elicit profound but often temporary anti-tumor responses in patients with BRAF(V600E) melanoma. Adaptive responses to RAF/MEK inhibition occur on a timescale of hours to days, involve homeostatic responses that reactivate MAP kinase signaling and compensatory mitogenic pathways, and attenuate the anti-tumor effects of RAF/MEK inhibitors. We profile adaptive responses across a panel of melanoma cell lines using multiplex biochemical measurement, single-cell assays, and statistical modeling and show that adaptation involves at least six signaling cascades that act to reduce drug potency (IC50) and maximal effect (i.e., E-max << 1). Among these cascades, we identify a role for JNK/c-Jun signaling in vemurafenib adaptation and show that RAF and JNK inhibitors synergize in cell killing. This arises because JNK inhibition prevents a subset of cells in a cycling population from becoming quiescent upon vemurafenib treatment, thereby reducing drug E-max. Our findings demonstrate the breadth and diversity of adaptive responses to RAF/MEK inhibition and a means to identify which steps in a signaling cascade are most predictive of phenotypic response. C1 [Fallahi-Sichani, Mohammad; Moerke, Nathan J.; Niepel, Mario; Sorger, Peter K.] Harvard Univ, Sch Med, Dept Syst Biol, HMS LINCS Ctr, Boston, MA 02115 USA. [Zhang, Tinghu; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Zhang, Tinghu; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Sorger, PK (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, HMS LINCS Ctr, Boston, MA 02115 USA. EM peter_sorger@hms.harvard.edu FU NIH LINCS Program [U54HG006097, U54HL127365]; [CA139980]; [CA130876] FX We thank C. Benes, A. Dastur, C. Shamu, David Wrobel, Jay Copeland, Elizabeth Williams, Jeremy Muhlich, Gabriel Berriz, Deborah Flusberg, and members of the ICCB-Longwood Screening Facility. We also thank Innopsys for early use of an InnoScan 710-IR scanner for analyzing RPPA slides. This work was supported by the NIH LINCS Program grant U54HG006097 and its continuation U54HL127365, by CA139980 (to PKS) and by CA130876 (to NSG). MF-S is a Merck Fellow of the Life Sciences Research Foundation. NR 67 TC 12 Z9 13 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD MAR PY 2015 VL 11 IS 3 AR 797 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CE4CA UT WOS:000351777200004 PM 25814555 ER PT J AU Stapleton, CJ Walcott, BP Fusco, MR Butler, WE Thomas, AJ Ogilvy, CS AF Stapleton, Christopher J. Walcott, Brian P. Fusco, Matthew R. Butler, William E. Thomas, Ajith J. Ogilvy, Christopher S. TI Surgical Management of Ruptured Middle Cerebral Artery Aneurysms With Large Intraparenchymal or Sylvian Fissure Hematomas SO NEUROSURGERY LA English DT Article DE Endovascular coil embolization; Intracranial aneurysm; Intraparenchymal hemorrhage; Microsurgical clip obliteration; Middle cerebral artery; Subarachnoid hemorrhage ID ENDOVASCULAR TREATMENT; SUBARACHNOID HEMORRHAGE; INTRACRANIAL ANEURYSMS; CLINICAL ARTICLE; INTRACEREBRAL HEMATOMA; BIFURCATION ANEURYSMS; CLOT EVACUATION; EMBOLIZATION; TRIAL; COILING AB BACKGROUND: Craniotomy for hematoma evacuation and aneurysm clipping is the treatment modality of choice for ruptured middle cerebral artery (MCA) aneurysms with intracranial hematomas. Recent literature suggests that endovascular coil embolization followed by hematoma evacuation can be an acceptable alternative. OBJECTIVE: To determine neurological outcomes in patients with ruptured MCA aneurysms and intraparenchymal or sylvian fissure hematomas. METHODS: The records of 49 patients with ruptured MCA aneurysms with large intracranial hematomas treated with hematoma evacuation and aneurysm clipping between January 2000 and December 2013 were retrospectively reviewed. RESULTS: Within this cohort, 35 patients (71.4%) were Hunt and Hess grade IV or V on presentation. The mean hematoma volume was 100.4 +/- 77.2 mL. Craniectomy was performed in 40 patients (81.6%). Angiographic vasospasm developed in 15 patients (30.6%). The in-hospital mortality rate was 28.6% (14 patients). At a mean of 25.3 +/- 34.0 months follow-up, a good outcome (modified Rankin Scale [mRS] score 0-3) was observed in 18 patients (36.7%). Significant factors associated with poor outcome or death (mRS scores of 4-6) included increasing age (P< .01), increasing Hunt and Hess grade (P = .03), increasing modified Fisher grade (P = .01), presence of intraventricular hemorrhage (P<.01), decreasing percentage of hematoma evacuation (P<.05), need for craniectomy (P<. 01), need for external ventricular drainage (P =.04), and angiographic vasospasm (P =.02). CONCLUSION: MCA aneurysm rupture with concomitant large intraparenchymal or sylvian fissure hematoma formation carries a grave prognosis. Simultaneous hematoma evacuation and aneurysm clipping with or without craniectomy can be an effective treatment modality. C1 [Stapleton, Christopher J.; Walcott, Brian P.; Butler, William E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Stapleton, Christopher J.; Walcott, Brian P.; Fusco, Matthew R.; Butler, William E.; Thomas, Ajith J.; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Boston, MA USA. [Fusco, Matthew R.; Thomas, Ajith J.; Ogilvy, Christopher S.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Neurosurg, Boston, MA 02215 USA. [Fusco, Matthew R.; Thomas, Ajith J.; Ogilvy, Christopher S.] Beth Israel Deaconess Med Ctr, Brain Aneurysm Inst, Boston, MA 02215 USA. RP Stapleton, CJ (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White 502, Boston, MA 02114 USA. EM cstapleton@mgh.harvard.edu NR 35 TC 5 Z9 7 U1 0 U2 2 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 MAR PY 2015 VL 76 IS 3 BP 258 EP 264 DI 10.1227/NEU.0000000000000596 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CC1PM UT WOS:000350113600013 PM 25603109 ER PT J AU Russo, ET Hulse, TE Adamkiewicz, G Levy, DE Bethune, L Kane, J Reid, M Shah, SN AF Russo, Elizabeth T. Hulse, Thomas E. Adamkiewicz, Gary Levy, Douglas E. Bethune, Leon Kane, John Reid, Margaret Shah, Snehal N. TI Comparison of Indoor Air Quality in Smoke-Permitted and Smoke-Free Multiunit Housing: Findings From the Boston Housing Authority SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; SECONDHAND SMOKE; PARTICULATE MATTER; 6 CITIES; EXPOSURE; POPULATION; PROTECTION; MORTALITY AB Introduction. Secondhand smoke remains a health concern for individuals living in multiunit housing, where smoke has been shown to easily transfer between units. Building-wide smoke-free policies are a logical step for minimizing smoke exposure in these settings. This evaluation sought to determine whether buildings with smoke-free policies have less secondhand smoke than similar buildings without such policies. Furthermore, this study assessed potential secondhand smoke transfer between apartments with and without resident smokers. Methods. Fine particulate matter (PM2.5), airborne nicotine, and self-reported smoking activity were recorded in 15 households with resident smokers and 17 households where no one smoked in 5 Boston Housing Authority developments. Of these, 4 apartment pairs were adjacent apartments with and without resident smokers. Halls between apartments and outdoor air were also monitored to capture potential smoke transfer and to provide background PM2.5 concentrations. Results. Households within buildings with smoke-free policies showed lower PM2.5 concentrations compared to buildings without these policies (median: 4.8 vs 8.1 mu g/m(3)). Although the greatest difference in PM2.5 between smoking-permitted and smoke-free buildings was observed in households with resident smokers (14.3 vs 7.0 mu g/m(3)), households without resident smokers also showed a significant difference (5.1 vs 4.0 mu g/m(3)). Secondhand smoke transfer to smoke-free apartments was demonstrable with directly adjacent households. Conclusion. This evaluation documented instances of secondhand smoke transfer between households as well as lower PM2.5 measurements in buildings with smoke-free policies. Building-wide smoke-free policies can limit secondhand smoke exposure for everyone living in multiunit housing. C1 [Russo, Elizabeth T.; Bethune, Leon; Reid, Margaret; Shah, Snehal N.] Boston Publ Hlth Commiss, Boston, MA 02118 USA. [Hulse, Thomas E.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Adamkiewicz, Gary] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Levy, Douglas E.] Massachusetts Gen Hosp, Dept Med, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Levy, Douglas E.] Harvard Univ, Sch Med, Boston, MA USA. [Kane, John] Boston Housing Author, Boston, MA USA. [Shah, Snehal N.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. RP Russo, ET (reprint author), Boston Publ Hlth Commiss, Res & Evaluat Off, 1010 Massachusetts Ave, Boston, MA 02118 USA. EM erusso@bphc.org FU Centers for Disease Control and Prevention [1U58DP002478-01]; CDC; Flight Attendants Medical Research Institute; Harvard School of Public Health/National Cancer Institute [P50-CA148596]; National Heart, Lung, and Blood Institute [R01-HL112212] FX The project was supported in part by the cooperative agreement with the Centers for Disease Control and Prevention (#1U58DP002478-01). Portions of this project's work involve the Communities Putting Prevention to Work initiative supported by CDC funding. DEL was supported by grants from the Flight Attendants Medical Research Institute, the Harvard School of Public Health/National Cancer Institute (P50-CA148596), and the National Heart, Lung, and Blood Institute (R01-HL112212). NR 22 TC 9 Z9 9 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAR PY 2015 VL 17 IS 3 BP 316 EP 322 DI 10.1093/ntr/ntu146 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA CD3AH UT WOS:000350949600007 PM 25156526 ER PT J AU Smolowitz, J Speakman, E Wojnar, D Whelan, EM Ulrich, S Hayes, C Wood, L AF Smolowitz, Janice Speakman, Elizabeth Wojnar, Danuta Whelan, Ellen-Marie Ulrich, Suzan Hayes, Carolyn Wood, Laura TI Role of the registered nurse in primary health care: Meeting health care needs in the 21st century SO NURSING OUTLOOK LA English DT Article DE Primary care; Primary health care; Registered nurse ID AMBULATORY-CARE; WORKFORCE; REFORM AB There is widespread interest in the redesign of primary health care practice models to increase access to quality health care. Registered nurses (RNs) are well positioned to assume direct care and leadership roles based on their understanding of patient, family, and system priorities. This project identified 16 exemplar primary health care practices that used RNs to the full extent of their scope of practice in team-based care. Interviews were conducted with practice representatives. RN activities were performed within three general contexts: episodic and preventive care, chronic disease management, and practice operations. RNs performed nine general functions in these contexts including telephone triage, assessment and documentation of health status; chronic illness case management, hospital transition management, delegated care for episodic illness, health coaching, medication reconciliation, staff supervision, and quality improvement leadership. These functions improved quality and efficiency and decreased cost. Implications for policy, practice, and RN education are considered. C1 [Smolowitz, Janice] Columbia Univ, Sch Nursing, New York, NY USA. [Speakman, Elizabeth] Thomas Jefferson Univ, Jefferson Interprofess Educ Ctr, Philadelphia, PA 19107 USA. [Wojnar, Danuta] Seattle Univ, Dept Maternal Child & Family Nursing, Seattle, WA 98122 USA. [Whelan, Ellen-Marie] Ctr Medicare Serv, Baltimore, MD USA. [Whelan, Ellen-Marie] Ctr Medicaid Serv, Baltimore, MD USA. [Ulrich, Suzan] St Catherine Univ, St Paul, MN USA. [Hayes, Carolyn] Dana Faber Canc Inst, Adult Inpatient & Integrat Oncol, Boston, MA USA. [Hayes, Carolyn] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wood, Laura] Boston Childrens Hosp, Boston, MA USA. RP Smolowitz, J (reprint author), 101 Carrollwood Dr, Tarrytown, NY 10591 USA. EM js928@columbia.edu FU Robert Wood Johnson Foundation Executive Nurse Fellow Program; American Academy of Nursing; American Board of Internal Medicine Foundation FX This work was funded by the Robert Wood Johnson Foundation Executive Nurse Fellow Program. The authors are grateful for the support and guidance provided by the American Academy of Nursing, specifically Joanne Disch, Joanne Pohl, Virginia Tilden and Cheryl Sullivan, and the American Board of Internal Medicine Foundation, specifically Thomas A. Sinsky and Daniel Wolfson. NR 38 TC 9 Z9 9 U1 2 U2 22 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 MAR-APR PY 2015 VL 63 IS 2 BP 130 EP 136 DI 10.1016/j.outlook.2014.08.004 PG 7 WC Nursing SC Nursing GA CD8CQ UT WOS:000351323200007 PM 25261382 ER PT J AU Buerhaus, PI DesRoches, CM Dittus, R Donelan, K AF Buerhaus, Peter I. DesRoches, Catherine M. Dittus, Robert Donelan, Karen TI Practice characteristics of primary care nurse practitioners and physicians SO NURSING OUTLOOK LA English DT Article DE Nurse practitioner practice characteristics; Primary care; Primary care nurse practitioners ID RANDOMIZED-TRIAL; OUTCOMES; SHORTAGE; COULD; TEAMS AB Background: Projections of physician shortages, an aging population, and insurance expansions have increased interest in expanding the number of primary care nurse practitioners (PCNPs) in the United States. Although information about the number and distribution of nurse practitioners is known, there is little information about the practice characteristics of PCNPs. The purpose of this study was to identify demographic and practice characteristics of PCNPs and compare these characteristics with primary care physicians (PCMDs). Methods: From November 23, 2011, to April 9, 2012, we conducted a national postal mail survey of 972 clinicians (467 PCNPs and 505 PCMDs). Questionnaire domains included compensation and billing practices; characteristics of patients treated; PCNPs' use of their own National Provider Identification number to bill services; how PCNPs spend their time; clinical and nonclinical activities performed; and whether PCNPs have privileges to admit, round on (i.e., oversee the care provided to) patients, and write orders independently of physicians. The response rate was 61.2%. Discussion: PCNPs are more likely than PCMDs to practice in urban and rural areas, provide care in a wider range of community settings, and treat Medicaid recipients and other vulnerable populations. Not only do most PCNPs work with PCMDs, but also the majority of both clinicians believe that increasing the supply of PCNPs will result in greater collaboration and team practice. Although PCNPs and PCMDs deliver similar services and spend their time in nearly identical ways, PCNPs work less hours and see fewer patients, and only a handful of PCNPs have their salary adjusted for productivity and quality performance. PCNPs cite government and local regulations as impeding their capacity to admit and round on patients in hospitals and long-term care facilities and write treatment orders without a physician cosignature. Conclusions: Significant differences in demographic and practice characteristics exist between PCNPs and PCMDs. Whether working independently or with PCMDs, increasing the number of PCNPs can be expected to expand access to primary care, particularly for vulnerable populations, and for those gaining access to health insurance through the Affordable Care Act. C1 [Buerhaus, Peter I.] Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Dept Hlth Policy, Nashville, TN 37203 USA. [DesRoches, Catherine M.] Math Policy Res, Cambridge, MA USA. [Dittus, Robert] Inst Med & Publ Hlth, Nashville, TN USA. [Dittus, Robert] VA Tennessee Valley Healthcare Syst, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Buerhaus, PI (reprint author), Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Dept Hlth Policy, Room 1203,2525 West End Ave, Nashville, TN 37203 USA. EM peter.buerhaus@vanderbilt.edu FU Robert Wood Johnson Foundation; Gordon & Betty Moore Foundation; Johnson & Johnson Campaign for Nursing's Future FX Supported by the The Robert Wood Johnson Foundation, Gordon & Betty Moore Foundation, and Johnson & Johnson Campaign for Nursing's Future. NR 28 TC 17 Z9 17 U1 0 U2 23 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 MAR-APR PY 2015 VL 63 IS 2 BP 144 EP 153 DI 10.1016/j.outlook.2014.08.008 PG 10 WC Nursing SC Nursing GA CD8CQ UT WOS:000351323200009 PM 25261383 ER PT J AU Ponte, PR Hayman, LL Berry, DL Cooley, ME AF Ponte, Patricia Reid Hayman, Laura L. Berry, Donna L. Cooley, Mary E. TI A new model for postdoctoral training: The Nursing Postdoctoral Program in Cancer and Health Disparities SO NURSING OUTLOOK LA English DT Article DE Cancer health disparities; Nursing research; Oncology nursing; Postdoctoral research fellowships; Research development ID OPPORTUNITIES; POPULATIONS; FACULTY AB The University of Massachusetts Boston and Dana-Farber/Harvard Cancer Center joined forces in 2009 to create a Postdoctoral Nursing Research Fellowship in Cancer and Health Disparities. In combining the resources of a large university and a research-intensive service institution, the postdoctoral program provides a new model for preparing nurse scientists to conduct independent research that advances nursing knowledge and interdisciplinary understanding of complex health issues. The multifaceted program consists of educational programming, research training, and career planning components. Additionally, each fellow is assigned a nurse scientist mentor and interdisciplinary co-mentor. The mentors support the fellows with scholarly activities and research training and help the fellows craft individualized career plans, including proposals for postfellowship career development research. In this article, the postdoctoral program leaders describe the program structure, strategies used to recruit minority and nonminority candidates, and data describing program outcomes and share lessons learned and recommendations for organizations that may be interested in establishing similar postdoctoral fellowships at their institutions. C1 [Ponte, Patricia Reid] Dana Farber Canc Inst, Nursing & Patient Care Serv, Boston, MA 02215 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Nursing & Patient Care Serv, Boston, MA 02115 USA. [Hayman, Laura L.; Cooley, Mary E.] Univ Massachusetts, Boston, MA 02125 USA. [Berry, Donna L.; Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. [Berry, Donna L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Ponte, PR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM pat_reid_ponte@dfci.harvard.edu FU National Cancer Institute U54 grant [U54CA156732] FX Supported by the National Cancer Institute U54 grant # U54CA156732. NR 22 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 0029-6554 EI 1528-3968 J9 NURS OUTLOOK JI Nurs. Outlook PD MAR-APR PY 2015 VL 63 IS 2 BP 189 EP 203 DI 10.1016/j.outlook.2014.11.014 PG 15 WC Nursing SC Nursing GA CD8CQ UT WOS:000351323200014 ER PT J AU Hollon, J Puppa, EL Greenwald, B Goldberg, E Guerrerio, A Fasano, A AF Hollon, Justin Puppa, Elaine Leonard Greenwald, Bruce Goldberg, Eric Guerrerio, Anthony Fasano, Alessio TI Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity SO NUTRIENTS LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; CLINICAL-RESPONSE; BARRIER FUNCTION; CONTROLLED-TRIAL; TIGHT JUNCTIONS; UNITED-STATES; FREE DIET; ZONULIN; INTERLEUKIN-10; INTOLERANCE AB Background: Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC). Methods: Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. Results: Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. Conclusions: Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity. C1 [Hollon, Justin] Naval Med Ctr Portsmouth, Dept Pediat Gastroenterol, Portsmouth, VA 23708 USA. [Puppa, Elaine Leonard] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Greenwald, Bruce; Goldberg, Eric] Univ Maryland, Div Gastroenterol & Hepatol, Sch Med, Baltimore, MD 21201 USA. [Guerrerio, Anthony] Johns Hopkins Univ, Div Pediat Gastroenterol & Nutr, Sch Med, Baltimore, MD 21205 USA. [Fasano, Alessio] Massachusetts Gen Hosp, Ctr Celiac Res, Boston, MA 02114 USA. [Fasano, Alessio] Massachusetts Gen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. RP Hollon, J (reprint author), Naval Med Ctr Portsmouth, Dept Pediat Gastroenterol, 620 John Paul Jones Circle, Portsmouth, VA 23708 USA. EM justin.hollon@med.navy.mil; eleonard@peds.umaryland.edu; bgreenwa@medicine.umaryland.edu; egoldber@medicine.umaryland.edu; aguerrerio@jhmi.edu; afasano@partners.org NR 28 TC 25 Z9 26 U1 4 U2 21 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD MAR PY 2015 VL 7 IS 3 BP 1565 EP 1576 DI 10.3390/nu7031565 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CE6EU UT WOS:000351930200007 PM 25734566 ER PT J AU Monlezun, DJ Bittner, EA Christopher, KB Camargo, CA Quraishi, SA AF Monlezun, Dominique J. Bittner, Edward A. Christopher, Kenneth B. Camargo, Carlos A. Quraishi, Sadeq A. TI Vitamin D Status and Acute Respiratory Infection: Cross Sectional Results from the United States National Health and Nutrition Examination Survey, 2001-2006 SO NUTRIENTS LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; LOCALLY WEIGHTED REGRESSION; ANTIMICROBIAL PEPTIDES; TRACT INFECTIONS; SEVERE INFLUENZA; D DEFICIENCY; RISK; ADULTS; CATHELICIDIN; METAANALYSIS AB Vitamin D is a promising, though under-explored, potential modifiable risk factor for acute respiratory infections (ARIs). We sought to investigate the association of vitamin D status with ARI in a large, nationally-representative sample of non-institutionalized individuals from the United States. We analyzed 14,108 individuals over 16 years of age in the National Health and Nutrition Survey (NHANES) 2001-2006 in this cross-sectional study. We used locally weighted scatterplot smoothing (LOWESS) to depict the relationship between increasing 25-hydroxyvitamin D (25OHD) levels and ARI. We then performed a multivariable regression analysis to investigate the association of 25OHD levels with ARI, while adjusting for known confounders. The median serum 25OHD level was 21 (IQR 15-27) ng/mL. Overall, 4.8% (95% CI: 4.5-5.2) of participants reported an ARI within 30 days before their participation in the national survey. LOWESS analysis revealed a near-linear relationship between vitamin D status and the cumulative frequency of ARI up to 25OHD levels around 30 ng/mL. After adjusting for season, demographic factors, and clinical data, 25OHD levels <30 ng/mL were associated with 58% higher odds of ARI (OR 1.58; 95% CI: 1.07-2.33) compared to levels >= 30 ng/mL. Among the 14,108 participants in NHANES 2001-2006, 25OHD levels were inversely associated with ARI. Carefully designed, randomized, controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of ARI. C1 [Monlezun, Dominique J.] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA 70112 USA. [Monlezun, Dominique J.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Bittner, Edward A.; Christopher, Kenneth B.; Camargo, Carlos A.; Quraishi, Sadeq A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bittner, Edward A.; Camargo, Carlos A.; Quraishi, Sadeq A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Camargo, Carlos A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Quraishi, SA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM dmonlezu@tulane.edu; eabittner@bics.bwh.harvard.edu; kbchristopher@partners.org; ccamargo@partners.org; squraishi@mgh.harvard.edu FU US National Institutes of Health [R01 AI093723, U01 AI087881, 5T32GM007592, UL1 RR025758] FX C.A.C. received support from the US National Institutes of Health R01 AI093723 and U01 AI087881. S.A.Q. received support from the US National Institutes of Health 5T32GM007592 and UL1 RR025758. NR 48 TC 3 Z9 3 U1 0 U2 2 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD MAR PY 2015 VL 7 IS 3 BP 1933 EP 1944 DI 10.3390/nu7031933 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CE6EU UT WOS:000351930200032 PM 25781219 ER PT J AU Saner, RJ Rathmell, JP AF Saner, Robert J. Rathmell, James P. TI CMS Asserts Broad Authority Over Physician Prescribing Practices SO PAIN MEDICINE LA English DT Editorial Material C1 [Saner, Robert J.] Pain Care Coalit, Washington, DC USA. [Saner, Robert J.] Powers Pyles Sutter & Verville PC, Washington, DC USA. [Rathmell, James P.] Pain Care Coalit, Washington, DC USA. [Rathmell, James P.] Massachusetts Gen Hosp, Div Pain Med, Dept Anesthesia, Boston, MA 02114 USA. [Rathmell, James P.] Harvard Univ, Sch Med, Anaesthesia, Boston, MA USA. RP Saner, RJ (reprint author), Pain Care Coalit, Washington, DC USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 2015 VL 16 IS 3 BP 421 EP 424 DI 10.1111/pme.12672 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CE0ZA UT WOS:000351538900005 PM 25786650 ER PT J AU Stojanovic, MP Higgins, DM Popescu, A Bogduk, N AF Stojanovic, Milan P. Higgins, Diana M. Popescu, Adrian Bogduk, Nikolai TI COMBI: A Convenient Tool for Clinical Outcome Assessment in Conventional Practice SO PAIN MEDICINE LA English DT Editorial Material ID RADIOFREQUENCY NEUROTOMY; IMMPACT RECOMMENDATIONS; ITEM BANK; PAIN; TRIALS C1 [Stojanovic, Milan P.; Higgins, Diana M.] VA Boston Healthcare Syst, Anesthesiol, Crit Care & Pain Med Serv, Boston, MA 02130 USA. [Higgins, Diana M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Popescu, Adrian] Univ Penn, Sch Med, Hosp Univ Penn, Philadelphia, PA 19104 USA. [Popescu, Adrian] VA Med Ctr, Rehabil Med Serv, Pain Med Serv, Philadelphia, PA USA. [Bogduk, Nikolai] Univ Newcastle, Fac Med & Hlth, Callaghan, NSW 2308, Australia. RP Stojanovic, MP (reprint author), VA Boston Healthcare Syst, Anesthesiol, Crit Care & Pain Med Serv, 150 South Huntington Ave, Boston, MA 02130 USA. EM mpstojanovic@gmail.com OI Higgins, Diana/0000-0002-6885-266X NR 19 TC 0 Z9 0 U1 3 U2 4 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 MAR PY 2015 VL 16 IS 3 BP 513 EP 519 DI 10.1111/pme.12581 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CE0ZA UT WOS:000351538900016 PM 25312899 ER PT J AU Ferraresi, C Kaippert, B Avci, P Huang, YY de Sousa, MVP Bagnato, VS Parizotto, NA Hamblin, MR AF Ferraresi, Cleber Kaippert, Beatriz Avci, Pinar Huang, Ying-Ying de Sousa, Marcelo V. P. Bagnato, Vanderlei S. Parizotto, Nivaldo A. Hamblin, Michael R. TI Low-level Laser (Light) Therapy Increases Mitochondrial Membrane Potential and ATP Synthesis in C2C12 Myotubes with a Peak Response at 3-6 h SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID CYTOCHROME-C-OXIDASE; SKELETAL-MUSCLE FATIGUE; BIPHASIC DOSE-RESPONSE; NEAR-IR RADIATION; ELECTRICAL-STIMULATION; MAMMALIAN-CELLS; IN-VITRO; IRRADIATION; NM; PHOTOTHERAPY AB Low-level laser (light) therapy has been used before exercise to increase muscle performance in both experimental animals and in humans. However, uncertainty exists concerning the optimum time to apply the light before exercise. The mechanism of action is thought to be stimulation of mitochondrial respiration in muscles, and to increase adenosine triphosphate (ATP) needed to perform exercise. The goal of this study was to investigate the time course of the increases in mitochondrial membrane potential (MMP) and ATP in myotubes formed from C2C12 mouse muscle cells and exposed to light-emitting diode therapy (LEDT). LEDT employed a cluster of LEDs with 20 red (630 +/- 10nm, 25mW) and 20 near-infrared (850 +/- 10nm, 50mW) delivering 28mWcm(2) for 90s (2.5Jcm(2)) with analysis at 5min, 3h, 6h and 24h post-LEDT. LEDT-6h had the highest MMP, followed by LEDT-3h, LEDT-24h, LEDT-5min and Control with significant differences. The same order (6h>3h>24h>5min> Control) was found for ATP with significant differences. A good correlation was found (r=0.89) between MMP and ATP. These data suggest an optimum time window of 3-6h for LEDT stimulate muscle cells. C1 [Ferraresi, Cleber; Parizotto, Nivaldo A.] Univ Fed Sao Carlos, Dept Phys Therapy, Lab Electrothermophototherapy, BR-13560 Sao Carlos, SP, Brazil. [Ferraresi, Cleber; Bagnato, Vanderlei S.; Parizotto, Nivaldo A.] Univ Fed Sao Carlos, Postgrad Program Biotechnol, BR-13560 Sao Carlos, SP, Brazil. [Ferraresi, Cleber; Bagnato, Vanderlei S.] Univ Sao Paulo, Phys Inst Sao Carlos, Opt Grp, Sao Carlos, SP, Brazil. [Ferraresi, Cleber; Kaippert, Beatriz; Avci, Pinar; Huang, Ying-Ying; de Sousa, Marcelo V. P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kaippert, Beatriz] Univ Fed Rio de Janeiro, Rio De Janeiro, RJ, Brazil. [Avci, Pinar; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [de Sousa, Marcelo V. P.] Univ Sao Paulo, Inst Phys, Lab Radiat Dosimetry & Med Phys, Sao Carlos, SP, Brazil. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI USP, CePOF/J-3608-2015; Ferraresi, Cleber/B-2458-2014; Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016 FU FAPESP [2010/07194-7, 2012/05919-0]; US NIH [R01AI050875] FX We thank Professor Zoltan Pierre Arany and his instructor Glenn C. Rowe for the C2C12 cells and Andrea Brissette for assistance with multiple roles including purchase of reagents. Cleber Ferraresi thank FAPESP for his PhD scholarships (numbers 2010/07194-7 and 2012/05919-0). MR Hamblin was supported by US NIH grant R01AI050875. NR 31 TC 15 Z9 15 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR-APR PY 2015 VL 91 IS 2 BP 411 EP 416 DI 10.1111/php.12397 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CD5JM UT WOS:000351123900020 PM 25443662 ER PT J AU Treister, N Li, SL Lerman, MA Lee, S Soiffer, R AF Treister, Nathaniel Li, Shuli Lerman, Mark A. Lee, Stephanie Soiffer, Robert TI Narrow-band UVB phototherapy for management of oral chronic graft-versus-host disease SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE graft-versus-host disease; oral mucosa; phototherapy ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; CLINICAL-TRIALS; CELL TRANSPLANTATION; PUVA TREATMENT; THERAPY; CRITERIA; CANCERS; MANIFESTATIONS; IRRADIATION AB ObjectivesOral chronic graft-versus-host disease (cGVHD) is a debilitating complication following allogeneic hematopoietic cell transplantation. The objective of this study was to evaluate the safety and efficacy of intraoral narrow-band ultraviolet B (NB-UVB) phototherapy in the management of oral cGVHD. MethodsPatients with oral cGVHD were treated using a custom NB-UVB unit for a course of 24 phototherapy sessions. Treatments were initiated at 50mJ/cm(2) and increased by 10% at each visit unless toxicity was noted. Toxicity and response were assessed weekly. ResultsEleven patients received a median of 22 (range 4-39) NB-UVB treatments; 5 patients completed 24 treatments and elected to receive a median of 7 additional treatments. Median symptom scores (0-10) for sensitivity, pain, and dryness at baseline/end of therapy were 7.5, 3, 1, and 3, 1, 2, respectively. Taking into account all patient-reported outcomes, 7/11 patients had improvement and 2/11 worsened. At least partial improvement was reported in 8/11 patients with none reporting worsening. Overtreatment occurred in 10/11 patients with all graded mild or moderate and resolving in 1-2 days. ConclusionsIntraoral NB-UVB may be effective for management of refractory oral cGVHD. Further optimization of treatment parameters, as well as minimal erythema dose testing, and inclusion of a control arm are necessary in the consideration of future studies. C1 [Treister, Nathaniel; Lerman, Mark A.] Dana Farber Brigham & Womens Canc Ctr, Div Oral Med & Dent, Boston, MA USA. [Li, Shuli] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Lee, Stephanie] Fred Hutchinson Canc Res Inst, Clin Res Div, Seattle, WA USA. [Soiffer, Robert] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Treister, N (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM ntreister@partners.org FU Division of Hematologic Malignancies, Dana-Farber Cancer Institute; [CA118953] FX This work was supported by grant CA118953 and the Division of Hematologic Malignancies, Dana-Farber Cancer Institute. We thank Mark Friedman and his colleagues at National Biological Corporation for custom designing and engineering the phototherapy unit. We would also like to thank Lei Zhao and Jennifer Brewer for their assistance with data analysis and manuscript preparation. We finally and most importantly extend our gratitude to our patients for participating in this clinical research protocol. NR 18 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-4383 EI 1600-0781 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD MAR PY 2015 VL 31 IS 2 BP 75 EP 82 DI 10.1111/phpp.12141 PG 8 WC Dermatology SC Dermatology GA CE0CC UT WOS:000351470000004 PM 25229419 ER PT J AU Tsai, SR Yin, R Huang, YY Sheu, BC Lee, SC Hamblin, MR AF Tsai, Shang-Ru Yin, Rui Huang, Ying-Ying Sheu, Bor-Ching Lee, Si-Chen Hamblin, Michael R. TI Low-level light therapy potentiates NPe6-mediated photodynamic therapy in a human osteosarcoma cell line via increased ATP SO PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY LA English DT Article DE Photodynamic therapy; Low level light therapy; Photobiomodulation; Mono-L-aspartyl chlorin(e6); Lysosomal uptake; Adenosine triphosphate ID LYSOSOMAL PHOTODAMAGE; INDUCED APOPTOSIS; INFRARED LIGHT; DRUG-DELIVERY; CYTOCHROME-C; CHLORIN E6; ACTIVATION; IRRADIATION; DEATH; PHOTOSENSITIZERS AB Background: Low-level light therapy (LLLT) is used to stimulate healing, reduce pain and inflammation, and preserve tissue from dying. LLLT has been shown to protect cells in culture from dying after various cytotoxic insults, and LLLT is known to increase the cellular ATP content. Previous studies have demonstrated that maintaining a sufficiently high ATP level is necessary for the efficient induction and execution of apoptosis steps after photodynamic therapy (PDT). Methods: We asked whether LLLT would protect cells from cytotoxicity due to PDT, or conversely whether LLLT would enhance the efficacy of PDT mediated by mono-L-aspartyl chlorin(e6) (NPe6). Increased ATP could lead to enhanced cell uptake of NPe6 by the energy dependent process of endocytosis, and also to more efficient apoptosis. In this study, human osteosarcoma cell line MG-63 was subjected to 1.5 J/cm(2) of 810 nm near infrared radiation (NIR) followed by addition of 10 mu M NPe6 and after 2 h incubation by 1.5 J/cm(2) of 652 nm red light for PDT. Results: PDT combined with LLLT led to higher cell death and increased intracellular reactive oxygen species compared to PDT alone. The uptake of NPe6 was moderately increased by LLLT, and cellular ATP was increased. The mitochondrial respiratory chain inhibitor antimycin A abrogated the LLLT-induced increase in cytotoxicity. Conclusions: Taken together, these results demonstrate that LLLT potentiates NPe6-mediated PDT via increased ATP synthesis and is a potentially promising strategy that could be applied in clinical PDT. (C) 2014 Elsevier B.V. All rights reserved. C1 [Tsai, Shang-Ru; Yin, Rui; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsai, Shang-Ru; Yin, Rui; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tsai, Shang-Ru; Lee, Si-Chen] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei 10764, Taiwan. [Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing, Peoples R China. [Sheu, Bor-Ching] Natl Taiwan Univ, Coll Med, Taipei, Taiwan. [Lee, Si-Chen] Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Wellman Ctr Photomed, 40 Blossom St,BAR414, Boston, MA 02114 USA. EM Hamblin@helix.mgh.harvard.edu OI Lee, Si-Chen/0000-0002-3788-2030; SHEU, BOR-CHING/0000-0003-1278-6082 FU US National Institutes of Health [R01AI050875]; National Science Council of Taiwan [NSC-102-2120-M-002-003] FX This work was supported by the US National Institutes of Health (R01AI050875). Shang-Ru Tsai was supported by the National Science Council of Taiwan (NSC-102-2120-M-002-003). NR 32 TC 5 Z9 5 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1572-1000 EI 1873-1597 J9 PHOTODIAGN PHOTODYN JI Photodiagnosis Photodyn. Ther. PD MAR PY 2015 VL 12 IS 1 BP 123 EP 130 DI 10.1016/j.pdpdt.2014.10.009 PG 8 WC Oncology SC Oncology GA CD6IR UT WOS:000351193300016 PM 25462575 ER PT J AU Toufaily, MH Westgate, MN Holmes, LB AF Toufaily, M. Hassan Westgate, Marie-Noel Holmes, Lewis B. TI Congenital talipes equinovarus: frequency of associated malformations not identified by prenatal ultrasound SO PRENATAL DIAGNOSIS LA English DT Article ID CLUB FOOT; DIAGNOSIS; POPULATION; FETUSES AB ObjectivesTo establish the frequency of prenatally undetected associated malformations (identified at birth) in infants with apparent isolated club foot deformity. MethodsA cohort study of all infants with unilateral or bilateral club foot deformity identified at birth among 311480 infants surveyed between 1972 and 2012 at Brigham and Women's Hospital in Boston. Those with talipes equinovarus were divided into isolated and complex, based on the findings in examination and by chromosome analysis. ResultsOne hundred and forty-two infants had isolated talipes equinovarus (TEV), and 66 had the complex type. Six (4.2%) of the 142 infants with isolated TEV were found at birth to have associated malformations that had not been identified by imaging during pregnancy. These abnormalities included hip dislocation (n=2), bilateral post-axial polydactyly of the feet (n=1), penile chordee (n=1), and hypospadias (n=2). ConclusionIn this consecutive series of infants with isolated talipes equinovarus, 95.8% had no additional malformations identified by examination at birth. None of the additional findings were severe enough to affect the medical prognosis of the affected infant. (c) 2014 John Wiley & Sons, Ltd. C1 [Toufaily, M. Hassan; Westgate, Marie-Noel; Holmes, Lewis B.] Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children,Med Genet Unit, Boston, MA 02115 USA. RP Toufaily, MH (reprint author), Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children,Med Genet Unit, Boston, MA 02115 USA. EM htoufaily@mgh.harvard.edu FU Birth Defects Registry of the Massachusetts Department of Public Health part of the National Birth Defects Prevention Study, a project of Birth Defects Center of the Centers for Disease Control, Atlanta FX Supported by funds provided by the Birth Defects Registry of the Massachusetts Department of Public Health, which is part of the National Birth Defects Prevention Study, a project of Birth Defects Center of the Centers for Disease Control, Atlanta. NR 16 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0197-3851 EI 1097-0223 J9 PRENATAL DIAG JI Prenat. Diagn. PD MAR PY 2015 VL 35 IS 3 BP 254 EP 257 DI 10.1002/pd.4534 PG 4 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA CD3LP UT WOS:000350980300008 PM 25394569 ER PT J AU Macera, MJ Sobrino, A Levy, B Jobanputra, V Aggarwal, V Mills, A Esteves, C Hanscom, C Pereira, S Pillalamarri, V Ordulu, Z Morton, CC Talkowski, M Warburton, D AF Macera, M. J. Sobrino, A. Levy, B. Jobanputra, V. Aggarwal, V. Mills, A. Esteves, C. Hanscom, C. Pereira, S. Pillalamarri, V. Ordulu, Z. Morton, C. C. Talkowski, M. Warburton, D. TI Prenatal diagnosis of chromothripsis, with nine breaks characterized by karyotyping, FISH, microarray and wholegenome sequencing SO PRENATAL DIAGNOSIS LA English DT Article ID CHROMOSOME REARRANGEMENTS; CATASTROPHIC EVENT; GERMLINE C1 [Macera, M. J.; Sobrino, A.; Mills, A.; Esteves, C.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Levy, B.; Jobanputra, V.; Aggarwal, V.] Columbia Univ, Dept Pathol, New York, NY USA. [Warburton, D.] Columbia Univ, Dept Genet & Dev, New York, NY 10027 USA. [Warburton, D.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Hanscom, C.; Pillalamarri, V.; Talkowski, M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Hanscom, C.; Pillalamarri, V.; Talkowski, M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hanscom, C.; Pillalamarri, V.; Talkowski, M.] Harvard Univ, Sch Med, Boston, MA USA. [Pereira, S.; Ordulu, Z.; Morton, C. C.] Harvard Univ, Sch Med, Dept Obstet, Boston, MA USA. [Pereira, S.; Ordulu, Z.; Morton, C. C.] Harvard Univ, Sch Med, Dept Gynecol, Boston, MA USA. [Pereira, S.; Ordulu, Z.; Morton, C. C.] Harvard Univ, Sch Med, Dept Reprod Biol, Boston, MA USA. [Ordulu, Z.; Morton, C. C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Pathol, Boston, MA 02115 USA. RP Warburton, D (reprint author), Columbia Univ, Dept Genet & Dev, New York, NY 10027 USA. EM dw9@cumc.columbia.edu FU NIH [R00MH095867, P01GM061354]; March of Dimes; Charles Hood Foundation FX NIH (R00MH095867, P01GM061354), the March of Dimes and the Charles Hood Foundation NR 8 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0197-3851 EI 1097-0223 J9 PRENATAL DIAG JI Prenat. Diagn. PD MAR PY 2015 VL 35 IS 3 BP 299 EP 301 DI 10.1002/pd.4456 PG 3 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA CD3LP UT WOS:000350980300015 PM 25043231 ER PT J AU Gendron, M Roberson, D Barrett, LF AF Gendron, Maria Roberson, Debi Barrett, Lisa Feldman TI Cultural Variation in Emotion Perception Is Real: A Response to Sauter, Eisner, Ekman, and Scott (2015) SO PSYCHOLOGICAL SCIENCE LA English DT Article ID FACIAL EXPRESSIONS; RECOGNITION; VOCALIZATIONS C1 [Gendron, Maria; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Roberson, Debi] Univ Essex, Dept Psychol, Colchester CO4 3SQ, Essex, England. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Barrett, LF (reprint author), Northeastern Univ, Psychol, 360 Huntington Ave,125 Nightingale Hall, Boston, MA 02115 USA. EM l.barrett@neu.edu FU National Institutes of Health Director's Pioneer Award [DP1OD003312] FX This research was supported by a National Institutes of Health Director's Pioneer Award (DP1OD003312) to L. F. Barrett. NR 13 TC 3 Z9 3 U1 1 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0956-7976 EI 1467-9280 J9 PSYCHOL SCI JI Psychol. Sci. PD MAR PY 2015 VL 26 IS 3 BP 357 EP 359 DI 10.1177/0956797614566659 PG 3 WC Psychology, Multidisciplinary SC Psychology GA CD9UJ UT WOS:000351443700012 PM 25608863 ER PT J AU Sloan, DM Vogt, D Wisco, BE Keane, TM AF Sloan, Denise M. Vogt, Dawne Wisco, Blair E. Keane, Terence M. TI Postdoctoral Training in Posttraumatic Stress Disorder Research SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE PTSD; trauma; training ID NATIONAL COMORBIDITY SURVEY; SURVEY-REPLICATION AB Postdoctoral training is increasingly common in the field of psychology. Although many individuals pursue postdoctoral training in psychology, guidelines for research training programs at this level do not exist. The rapid advances in the field, particularly with respect to genetics, neuroimaging, and data analytic approaches, require clinical scientists to possess knowledge and expertise across a broad array of areas. Postdoctoral training is often needed to acquire such a skill set. This paper describes a postdoctoral training program designed for individuals pursuing academic careers in traumatic stress disorders research. In this paper, we describe the structure of our training program, challenges we have faced during the 15 years of its existence, and how we have addressed these challenges. We conclude with a presentation of outcome data for the training program and a discussion of how training programs in other settings might be structured. C1 [Sloan, Denise M.; Vogt, Dawne; Wisco, Blair E.; Keane, Terence M.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA 02130 USA. [Sloan, Denise M.; Vogt, Dawne; Wisco, Blair E.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, VA Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM Denise.Sloan@va.gov NR 12 TC 0 Z9 0 U1 4 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAR PY 2015 VL 7 IS 2 BP 195 EP 202 DI 10.1037/tra0000007 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CD9EA UT WOS:000351399300012 PM 25793697 ER PT J AU Win, AZ Aparici, CM AF Win, A. Z. Aparici, C. M. TI Non-traumatic radiation-induced avascular necrosis of the femoral neck SO QJM-AN INTERNATIONAL JOURNAL OF MEDICINE LA English DT Editorial Material ID HIP C1 [Win, A. Z.] San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA 94121 USA. [Aparici, C. M.] UCSF, Dept Radiol, San Francisco, CA 94143 USA. RP Win, AZ (reprint author), San Francisco VA Med Ctr, Dept Radiol, 4150 Clement St, San Francisco, CA 94121 USA. EM aungzwin@gmail.com NR 5 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1460-2725 EI 1460-2393 J9 QJM-INT J MED JI QJM-An Int. J. Med. PD MAR 1 PY 2015 VL 108 IS 3 BP 257 EP 258 DI 10.1093/qjmed/hcu190 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CE0UN UT WOS:000351522900018 PM 25208894 ER PT J AU Win, AZ Aparici, CM AF Win, A. Z. Aparici, C. M. TI Distant bone metastasis from supraglottic squamous cell carcinoma SO QJM-AN INTERNATIONAL JOURNAL OF MEDICINE LA English DT Editorial Material ID NECK C1 [Win, A. Z.] San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA 94121 USA. [Aparici, C. M.] UCSF, Dept Radiol, San Francisco, CA 94143 USA. RP Win, AZ (reprint author), San Francisco VA Med Ctr, Dept Radiol, 4150 Clement St, San Francisco, CA 94121 USA. EM aungzwin@gmail.com NR 5 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1460-2725 EI 1460-2393 J9 QJM-INT J MED JI QJM-An Int. J. Med. PD MAR 1 PY 2015 VL 108 IS 3 BP 259 EP 260 DI 10.1093/qjmed/hcu199 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CE0UN UT WOS:000351522900019 PM 25223573 ER PT J AU Tiourin, E Velasco, VS Rosales, MA Sullivan, PS Janzen, DM Memarzadeh, S AF Tiourin, Ekaterina Velasco, Victor S. Rosales, Miguel A. Sullivan, Peggy S. Janzen, Deanna M. Memarzadeh, Sanaz TI Tubal Ligation May Induce Quiescence of Distal Fallopian Tube Epithelia: A Potential Mechanism for Risk Reduction of Serous Carcinomas SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Tiourin, Ekaterina; Velasco, Victor S.; Rosales, Miguel A.; Janzen, Deanna M.; Memarzadeh, Sanaz] Univ Calif Los Angeles, David Geffen Sch Med, Obstet & Gynecol, Los Angeles, CA 90095 USA. [Sullivan, Peggy S.] Univ Calif Los Angeles, David Geffen Sch Med, Pathol & Lab Med, Los Angeles, CA 90095 USA. [Memarzadeh, Sanaz] Univ Calif Los Angeles, Broad Ctr Regenerat Med & Stem Cell Res, Los Angeles, CA USA. [Memarzadeh, Sanaz] VA Greater Los Angeles Hlth Care Syst, Gynecol Oncol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA O-017 BP 62A EP 62A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407200018 ER PT J AU Styer, AK Gaskins, AJ Brady, P Sluss, P Chavarro, JE Hauser, R Toth, TL AF Styer, Aaron K. Gaskins, Audrey J. Brady, Paula Sluss, Patrick Chavarro, Jorge E. Hauser, Russ Toth, Thomas L. TI The Rate of Serum AMH Decline During Controlled Ovarian Hyperstimulation Is Predictive of IVF Response and Clinical Pregnancy SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Obstet Gynecol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA O-048 BP 72A EP 72A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407200049 ER PT J AU Chattergoon, NN Louey, S Scanlan, T Giraud, GD Thornburg, KL AF Chattergoon, N. N. Louey, S. Scanlan, T. Giraud, G. D. Thornburg, K. L. TI Blockade of T-3 Reveals the Maturation of p21 Signaling in Fetal Cardiomyocytes SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Chattergoon, N. N.; Louey, S.; Giraud, G. D.; Thornburg, K. L.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA. [Louey, S.; Scanlan, T.; Thornburg, K. L.] Oregon Hlth & Sci Univ, Physiol & Pharmacol, Portland, OR 97201 USA. [Giraud, G. D.] Portland VA Med Ctr, Cardiol, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA O-090 BP 85A EP 86A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407200091 ER PT J AU Vincent, K Berna, C Kennedy, S Moore, J AF Vincent, Katy Berna, Chantal Kennedy, Stephen Moore, Jane TI Factors Other Than Pain Intensity Predict Reduced Quality of Life in Women With Chronic Pelvic Pain SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Vincent, Katy; Kennedy, Stephen; Moore, Jane] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England. [Berna, Chantal] Massachusetts Gen Hosp, Dept Anaesthesia, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA T-007 BP 110A EP 111A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407201037 ER PT J AU Naqvi, M Goldfarb, I Barth, WH Kaimal, A AF Naqvi, Mariam Goldfarb, Ilona Barth, William H., Jr. Kaimal, Anjali TI Who Chooses a Trial of Labor? SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Naqvi, Mariam; Goldfarb, Ilona; Barth, William H., Jr.; Kaimal, Anjali] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA T-115 BP 145A EP 145A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407201144 ER PT J AU Bryant, AS Nakagawa, S Norton, ME Bishop, JT Pena, S Gregorich, SE Kuppermann, M AF Bryant, Allison S. Nakagawa, Sanae Norton, Mary E. Bishop, Judith T. Pena, Sherri Gregorich, Steven E. Kuppermann, Miriam TI Invasive Testing for Aneuploidy: Do We Practice What We Preach? SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Bryant, Allison S.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Nakagawa, Sanae; Norton, Mary E.; Bishop, Judith T.; Pena, Sherri; Kuppermann, Miriam] Univ Calif San Francisco, Obstet & Gynecol, San Francisco, CA 94143 USA. [Gregorich, Steven E.] Univ Calif San Francisco, Med, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA T-200 BP 171A EP 171A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407201228 ER PT J AU Naqvi, M Hanmer, K Goldfarb, I Bryant, A AF Naqvi, Mariam Hanmer, Kaitlin Goldfarb, Ilona Bryant, Allison TI Chromosomal Microarray Analysis Uptake in Women Undergoing Invasive Prenatal Testing: A Single Institution Experience SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Naqvi, Mariam; Hanmer, Kaitlin; Goldfarb, Ilona; Bryant, Allison] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA T-212 BP 175A EP 175A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407201240 ER PT J AU Ondersma, SJ Beatty, JR Svikis, DS Chang, G Tzilos, GK Strickler, RC Rice, S Graham, AE Sokol, RJ AF Ondersma, Steven J. Beatty, Jessica R. Svikis, Dace S. Chang, Grace Tzilos, Golfo K. Strickler, Ronald C. Rice, Shetoya Graham, Amy E. Sokol, Robert J. TI Pregnancy Outcomes Following a Computer-Delivered Brief Intervention for Alcohol Use During Pregnancy: Results From a Pilot Randomized Trial SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Ondersma, Steven J.; Beatty, Jessica R.; Rice, Shetoya; Graham, Amy E.] Wayne State Univ, Merrill Palmer Skillman Inst, Detroit, MI USA. [Svikis, Dace S.] Virginia Commonwealth Univ, Inst Womens Hlth, AWHARE, Richmond, VA USA. [Chang, Grace] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. [Tzilos, Golfo K.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Strickler, Ronald C.] Henry Ford Hlth Syst, Womens Hlth, Obstet, Educ& Res,Gynecol, Detroit, MI USA. [Sokol, Robert J.] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA T-225 BP 179A EP 179A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407201253 ER PT J AU Gray, KJ Kovacheva, VP Mirzakhani, H Bjonnes, A Keating, B Bateman, BT Saxena, R AF Gray, Kathryn J. Kovacheva, Vesela P. Mirzakhani, Hooman Bjonnes, Andrew Keating, Brendan Bateman, Brian T. Saxena, Richa TI Risk of Preeclampsia in Patients With Genetic Predisposition To Common Medical Conditions SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Gray, Kathryn J.] Brigham & Womens Hosp, Maternal Fetal Med, Boston, MA 02115 USA. [Kovacheva, Vesela P.] Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. [Mirzakhani, Hooman; Bateman, Brian T.; Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bjonnes, Andrew; Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Keating, Brendan] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA T-291 BP 200A EP 200A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407202053 ER PT J AU Phillippe, M Berk, TK AF Phillippe, Mark Berk, Tucker K. TI Cell-free Fetal DNA: Hypomethylated and Stimulates TLR9 Mediated IL6 Production SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Phillippe, Mark; Berk, Tucker K.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA F-117 BP 241A EP 241A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407202183 ER PT J AU Bryant, AS Nseyo, O Nakagawa, S Gregorich, S Kuppermann, M AF Bryant, Allison S. Nseyo, Onouwem Nakagawa, Sanae Gregorich, Steven Kuppermann, Miriam TI Birth Spacing: What Do Women Intend? SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Bryant, Allison S.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Nseyo, Onouwem; Nakagawa, Sanae; Kuppermann, Miriam] Univ Calif San Francisco, Obstet & Gynecol, San Francisco, CA 94143 USA. [Gregorich, Steven] Univ Calif San Francisco, Med, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA F-186 BP 263A EP 263A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407202252 ER PT J AU Stanic, AK Young, BC Karmon, AE Rueda, BR AF Stanic, Aleksandar K. Young, Brett C. Karmon, Anatte E. Rueda, Bo R. TI Longitudinal Changes in Dendritic Cells Response To Toll-Like Receptor Stimulation in Uncomplicated Pregnancy and Postpartum. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Young, Brett C.; Karmon, Anatte E.; Rueda, Bo R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Ob Gyn, Boston, MA USA. [Stanic, Aleksandar K.] Univ Wisconsin, Div Reprod Sci, Dept Ob Gyn, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA S-078 BP 323A EP 323A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407202441 ER PT J AU Venkatesh, KK Rae-Easter, S Molina, R Kaimal, A Tuomala, R Riley, L AF Venkatesh, Kartik K. Rae-Easter, Sarah Molina, Rose Kaimal, Anjali Tuomala, Ruth Riley, Laura TI Clinical Predictors of Peripartum Bacteremia. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract C1 [Venkatesh, Kartik K.; Rae-Easter, Sarah; Molina, Rose; Kaimal, Anjali; Tuomala, Ruth; Riley, Laura] Massachusetts Gen Hosp, Brigham & Womens Hosp, OB GYN, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2015 VL 22 SU 1 MA S-176 BP 354A EP 355A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CD9GW UT WOS:000351407202539 ER PT J AU Spielberg, JM Forbes, EE Ladouceur, CD Worthman, CM Olino, TM Ryan, ND Dahl, RE AF Spielberg, Jeffrey M. Forbes, Erika E. Ladouceur, Cecile D. Worthman, Carol M. Olino, Thomas M. Ryan, Neal D. Dahl, Ronald E. TI Pubertal testosterone influences threat-related amygdala-orbitofrontal cortex coupling SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE puberty; testosterone; amygdale; OFC; threat; connectivity ID ORBITAL PREFRONTAL CORTEX; DECISION-MAKING; EMOTION REGULATION; ADOLESCENT BRAIN; BEHAVIOR; CONNECTIVITY; RESPONSES; DISPLAYS; PERIOD AB Growing evidence indicates that normative pubertal maturation is associated with increased threat reactivity, and this developmental shift has been implicated in the increased rates of adolescent affective disorders. However, the neural mechanisms involved in this pubertal increase in threat reactivity remain unknown. Research in adults indicates that testosterone transiently decreases amygdala-orbitofrontal cortex (OFC) coupling. Consequently, we hypothesized that increased pubertal testosterone disrupts amygdala-OFC coupling, which may contribute to developmental increases in threat reactivity in some adolescents. Hypotheses were tested in a longitudinal study by examining the impact of testosterone on functional connectivity. Findings were consistent with hypotheses and advance our understanding of normative pubertal changes in neural systems instantiating affect/motivation. Finally, potential novel insights into the neurodevelopmental pathways that may contribute to adolescent vulnerability to behavioral and emotional problems are discussed. C1 [Spielberg, Jeffrey M.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Forbes, Erika E.; Ladouceur, Cecile D.; Olino, Thomas M.; Ryan, Neal D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Worthman, Carol M.] Emory Univ, Dept Anthropol, Atlanta, GA USA. [Dahl, Ronald E.] Univ Calif Berkeley, Inst Human Dev, Dept Psychol, Berkeley, CA 94720 USA. RP Spielberg, JM (reprint author), VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, 150 South Huntington Ave 182 JP, Boston, MA 02130 USA. EM spielbergjm@gmail.com RI Ladouceur, C/H-3124-2016; OI Forbes, Erika/0000-0003-0659-7744; Spielberg, Jeffrey/0000-0001-8348-7157 FU National Institute on Drug Abuse [R01 DA018910] FX This work was supported by the National Institute on Drug Abuse (R01 DA018910). NR 34 TC 11 Z9 11 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD MAR PY 2015 VL 10 IS 3 BP 408 EP 415 DI 10.1093/scan/nsu062 PG 8 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CE0VI UT WOS:000351526400013 PM 24795438 ER PT J AU Tabernero, J Chawla, SP Kindler, H Reckamp, K Chiorean, EG Azad, NS Lockhart, AC Hsu, CP Baker, NF Galimi, F Beltran, P Baselga, J AF Tabernero, Josep Chawla, Sant P. Kindler, Hedy Reckamp, Karen Chiorean, E. Gabriela Azad, Nilofer S. Lockhart, A. Craig Hsu, Cheng-Pang Baker, Nigel F. Galimi, Francesco Beltran, Pedro Baselga, Jose TI Anticancer activity of the type I insulin-like growth factor receptor antagonist, ganitumab, in combination with the death receptor 5 agonist, conatumumab SO TARGETED ONCOLOGY LA English DT Article DE Monoclonal antibodies; Insulin-like growth factor receptor; Death receptor; TRAIL; Apoptosis; Targeted therapy ID ADVANCED SOLID TUMORS; COLON-CANCER CELLS; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; TYROSINE KINASE; COLORECTAL-CANCER; DRUG-DEVELOPMENT; CLINICAL-TRIALS; DOSE-ESCALATION; CARCINOMA CELLS AB Agents targeting the insulin-like growth factor receptor type 1 (IGF1R) have shown antitumor activity. Based on the evidence for interaction between the IGF-1 and TRAIL pathways, we hypothesized that the combination of ganitumab (monoclonal antibody to IGF1R) with the pro-apoptotic death receptor 5 agonist, conatumumab, might increase antitumor response. Ganitumab and conatumumab were tested in combination in a Colo-205 xenograft model. Part 1 of the clinical study was a phase Ib program of three doses of conatumumab (1, 3, 15 mg/kg) in combination with 18 mg/kg ganitumab to determine the maximum tolerated dose (MTD) in patients with advanced solid tumors. Part 2 was conducted in six cohorts with advanced non-small cell lung cancer (squamous or non-squamous histology), colorectal cancer, sarcoma, pancreatic cancer, or ovarian cancer, treated at the recommended doses of the combination. The combination was significantly more active in the Colo-205 xenograft model than either single agent alone (p < 0.0015). In part 1 of the clinical study, no dose-limiting toxicities were observed and the MTD of conatumumab was 15 mg/kg in combination with 18 mg/kg ganitumab. In part 2, 78 patients were treated and there were no objective responses but 28 patients (36 %) had stable disease (median 46 days, range 0-261). The combination was well-tolerated with no new toxicities. In conclusion, the combination of ganitumab and conatumumab was well-tolerated but had no objective responses in the population tested. The successful future application of this combination of antitumor mechanisms may rely on the identification of predictive biomarkers. C1 [Tabernero, Josep] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Barcelona 08035, Spain. [Tabernero, Josep] Univ Autonoma Barcelona, Inst Oncol VHIO, Barcelona 08035, Spain. [Chawla, Sant P.] Sarcoma Oncol Ctr, Santa Monica, CA USA. [Kindler, Hedy] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. [Reckamp, Karen] City Hope Natl Med Ctr, Comprehens Canc Ctr Med Oncol, Duarte, CA 91010 USA. [Chiorean, E. Gabriela] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Azad, Nilofer S.] John Hopkins Med Ctr, Baltimore, MD USA. [Lockhart, A. Craig] Washington Univ, Sch Med, St Louis, MO USA. [Hsu, Cheng-Pang; Galimi, Francesco; Beltran, Pedro] Amgen Inc, Thousand Oaks, CA 91320 USA. [Baker, Nigel F.] Amgen Ltd, Cambridge, England. [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Tabernero, J (reprint author), Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Passeig Vall dHebron 119-129, Barcelona 08035, Spain. EM jtabernero@vhio.net OI Reckamp, Karen/0000-0002-9213-0325 FU Amgen Inc., Thousand Oaks CA, USA FX This work was sponsored by Amgen Inc., Thousand Oaks CA, USA. Wanda J. Krall, PhD, on behalf of Amgen Inc., and Kathryn Boorer, PhD, of Amgen Inc. assisted the authors in the writing of the manuscript. NR 50 TC 6 Z9 8 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1776-2596 EI 1776-260X J9 TARGET ONCOL JI Target. Oncol. PD MAR PY 2015 VL 10 IS 1 BP 65 EP 76 DI 10.1007/s11523-014-0315-z PG 12 WC Oncology SC Oncology GA CE0UF UT WOS:000351521900006 PM 24816908 ER PT J AU Gupta, S Fenves, A Nance, ST Sykes, DB Dzik, W AF Gupta, Shruti Fenves, Andrew Nance, Sandra Taddie Sykes, David B. Dzik, Walter Sunny TI Hyperhemolysis syndrome in a patient without a hemoglobinopathy, unresponsive to treatment with eculizumab SO TRANSFUSION LA English DT Article ID SICKLE-CELL-DISEASE; HEMOLYTIC TRANSFUSION REACTIONS; RED-CELLS; HYPERHAEMOLYSIS; DESTRUCTION AB BackgroundHyperhemolysis is a serious transfusion reaction, most often described in patients with hemoglobinopathies. Hyperhemolysis is characterized by the destruction of host red blood cells (RBCs), in addition to donor RBCs, via an unknown mechanism. Study Design and MethodsWe present the case of a 58-year-old woman with treated human immunodeficiency virus and a normal hemoglobin (Hb) electrophoresis who developed hyperhemolysis in the setting of a delayed hemolytic transfusion reaction (DHTR). ResultsThe patient was ABO group B and had a previously identified anti-Fy(b) alloantibody. After transfusion of Fy(b)- RBCs, she developed a DHTR and was found to have anti-E, anti-C-w, anti-s, and an additional antibody to an unrecognized high-frequency RBC alloantigen. Subsequent transfusion of ABO-compatible RBCs that were negative for Fy(b), E, C-w, and s antigens resulted in immediate intravascular hemolysis. In the absence of bleeding, her hematocrit (Hct) decreased to 10.2%. An extensive serologic evaluation failed to identify the specificity of the high-frequency antibody. Severe hemolytic reactions also occurred despite pretransfusion conditioning with eculizumab. The Hct and clinical symptoms slowly improved after the cessation of transfusions and treatment with erythropoietin and steroids. This case demonstrates several noteworthy features including hyperhemolysis in a patient without a Hb disorder, the development of an antibody to an unknown RBC antigen, and the failure of eculizumab to prevent intravascular hemolysis after transfusion. ConclusionHyperhemolysis is not restricted to patients with hemoglobinopathies. Whether eculizumab offers any benefit in the hyperhemolysis syndrome or in the prevention of intravascular hemolysis due to RBC alloantibodies remains uncertain. C1 [Gupta, Shruti; Fenves, Andrew; Sykes, David B.; Dzik, Walter Sunny] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Nance, Sandra Taddie] Amer Red Cross, Biomed Serv, Philadelphia, PA USA. RP Dzik, W (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224, Boston, MA 02114 USA. EM sdzik@partners.org NR 22 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD MAR PY 2015 VL 55 IS 3 BP 623 EP 628 DI 10.1111/trf.12876 PG 6 WC Hematology SC Hematology GA CD6BZ UT WOS:000351175100024 PM 25257194 ER PT J AU Wachterman, MW McCarthy, EP Marcantonio, ER Ersek, M AF Wachterman, M. W. McCarthy, E. P. Marcantonio, E. R. Ersek, M. TI Mistrust, Misperceptions, and Miscommunication: A Qualitative Study of Preferences About Kidney Transplantation Among African Americans SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID STAGE RENAL-DISEASE; RACIAL-DIFFERENCES; UNITED-STATES; REPLACEMENT THERAPIES; DONOR KIDNEYS; ACCESS; RACE; DISPARITIES; HEMODIALYSIS; DIALYSIS AB Background. Kidney transplantation rates in the United States are lower among African Americans than among whites. Well-documented racial disparities in access to transplantation explain some, but not all, of these differences. Prior survey-based research suggests that African American dialysis patients are less likely than whites to desire transplantation, but little research has focused on an in-depth exploration of preferences about kidney transplantation among African Americans. Thus, the purposes of this study were to explore preferences and to compare patients' expectations about transplantation with actual status on the transplant list. Methods. We conducted semistructured interviews with 16 African Americans receiving chronic hemodialysis. We analyzed the interviews using the constant comparative method of qualitative analysis. We also reviewed the dialysis center's transplant list. Results. Four dominant themes emerged: (1) varied desire for transplant; (2) concerns about donor source; (3) barriers to transplantation; and (4) lack of communication with nephrologists and the transplantation team. A thread of mistrust about equity in the transplantation process flowed through themes 2-4. In 7/16 cases, patients' understanding of their transplant listing status was discordant with their actual status. Conclusions. Our study suggests that many African Americans on hemodialysis are interested in kidney transplantation, but that interest is often tempered by concerns about transplantation, including misconceptions about the risks to recipients and donors. Mistrust about equity in the organ allocation process also contributed to ambivalence. The discordance between patients' perceptions of listing status and actual status suggests communication gaps between African American hemodialysis patients and physicians. Clinicians should avoid interpreting ambivalence about transplantation as lack of interest. C1 [Wachterman, M. W.] VA Boston Healthcare Syst, Sect Gen Internal Med, Boston, MA 02130 USA. [Wachterman, M. W.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Wachterman, M. W.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Wachterman, M. W.; McCarthy, E. P.; Marcantonio, E. R.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Wachterman, M. W.; McCarthy, E. P.; Marcantonio, E. R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [McCarthy, E. P.] Harvard Univ, Sch Med, Off Divers Inclus & Community Partnership, Boston, MA USA. [Marcantonio, E. R.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Ersek, M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Wachterman, M. W.; Ersek, M.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Wachterman, MW (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave,Bldg 9, Boston, MA 02130 USA. EM melissa.wachterman@va.gov FU Ruth L. Kirschstein National Research Service Awards (NRSA) from the National Institute of Nursing Research [1F32NR012872-01]; Mid-career Investigator Award in Patient-Oriented Research from the National Institute on Aging [K24 AG035075] FX Dr. Wachterman was supported by a Ruth L. Kirschstein National Research Service Awards (NRSA) for Individual Postdoctoral Fellows (1F32NR012872-01) from the National Institute of Nursing Research. Dr. Marcantonio was supported by a Mid-career Investigator Award in Patient-Oriented Research from the National Institute on Aging (K24 AG035075). NR 47 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 0041-1345 EI 1873-2623 J9 TRANSPL P JI Transplant. Proc. PD MAR PY 2015 VL 47 IS 2 BP 240 EP 246 DI 10.1016/j.transproceed.2015.01.016 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA CE0FT UT WOS:000351480600002 PM 25769556 ER PT J AU Crevensten, H AF Crevensten, Henry TI Patients Recovering from Abdominal Surgery Who Walked with Volunteers Exhibited Improved Postoperative Recovery Profiles During Hospitalization: Reply SO WORLD JOURNAL OF SURGERY LA English DT Letter C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Crevensten, H (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM hcrevensten@medicine.ucsf.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD MAR PY 2015 VL 39 IS 3 BP 807 EP 807 DI 10.1007/s00268-014-2907-2 PG 1 WC Surgery SC Surgery GA CD6WM UT WOS:000351230900041 PM 25575459 ER PT J AU Sedlacik, J Reitz, M Bolar, DS Adalsteinsson, E Schmidt, NO Fiehler, J AF Sedlacik, Jan Reitz, Matthias Bolar, Divya S. Adalsteinsson, Elfar Schmidt, Nils O. Fiehler, Jens TI Correlation of oxygenation and perfusion sensitive MRI with invasive micro probe measurements in healthy mice brain SO ZEITSCHRIFT FUR MEDIZINISCHE PHYSIK LA English DT Article DE qBOLD; ASL; hypercapnia; hyperoxia ID CEREBRAL BLOOD-VOLUME; POSITRON-EMISSION-TOMOGRAPHY; EXTRACTION FRACTION; CARBON-DIOXIDE; COMPUTED-TOMOGRAPHY; QUANTITATIVE BOLD; SIGNAL BEHAVIOR; SUSCEPTIBILITY; ANESTHETICS; VALIDATION AB The non-invasive assessment of (patho-)physiological parameters such as, perfusion and oxygenation, is of great importance for the characterization of pathologies e.g., tumors, which may be helpful to better predict treatment response and potential outcome. To better understand the influence of physiological parameters on the investigated oxygenation and perfusion sensitive MRI methods, MRI measurements were correlated with subsequent invasive micro probe measurements during free breathing conditions of air air+10% CO2 and 100% O2 in healthy mice brain. MRI parameters were the irreversible (R2), reversible (R2') and effective (R2*) transverse relaxation rates, venous blood oxygenation level assessed by quantitative blood oxygenation level dependent (qBOLD) method and cerebral blood flow (CBF) assessed by arterial spin labeling (ASL) using a 7T small animal MRI scanner One to two days after MRI, tissue peditsion and pO2 were measured by Laser-Doppler flowmetry and fluorescence quenching micro probes, respectively. The tissue pO2 values were converted to blood oxygen saturation by using the Hill equation. The animals were anesthetized by infra peritoneal injection of ketamine-xylazine-acepromazine (10-2-0.3 mg/ml.kg). Results for nonnal/hypercapnia/hyperoxia conditions were: R2[s(boolean AND)-1] = 20.7/20.4/20.1, R2*[s(boolean AND)-1] = 31.6/29.6/25.9, R2[s-(boolean AND)] = 10.9/9.2/5.7, qBOLD venous blood oxygenation level = 0.43/0.51/0.56, CBF[ml.min(boolean AND) -1.100g(boolean AND)-1] = 70.6/105.5/81.8, Laser-Doppler flowmetry[a.u.] = 89.2/120.2/90.6 and pO2[mmHg] = 6.3/32.3/46.7. All parameters were statistically significantly different with P < 0.001 between all breathing conditions. All MRI and the corresponding micro probe measurements were also statistically significantly (P <= 0.03) correlated with each other. Howeven converting the tissue pO2 to blood oxygen saturation = 0.02/0.34/0.63, showed only very limited agreement with the qBOLD venous blood oxygenation level. We found good correlation between MRI and micro probe measurements. However, direct conversion of tissue pO2 to blood oxygen saturation by using the Hill equation is very limited. Furthermore, adverse effects of anesthesia and trauma due to micro probe insertion are strong confounding factors and need close attention for study planning and conduction of experiments. Investigation of the correlation of perfusion and oxygenation sensitive MRI nzethods with micro probe measurements in pathologic tissue such as tumors is now of compelling interest. C1 [Sedlacik, Jan; Fiehler, Jens] Univ Med Ctr Hamburg Eppendorf, Neuroradiol, D-20246 Hamburg, Germany. [Reitz, Matthias; Schmidt, Nils O.] Univ Med Ctr Hamburg Eppendorf, Neurosurg, D-20246 Hamburg, Germany. [Bolar, Divya S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Radiol, Charlestown, MA USA. [Adalsteinsson, Elfar] MIT, Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Sedlacik, J (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Diagnost & Intervent Neuroradiol, Martinistr 52, D-20246 Hamburg, Germany. EM j.sedlacik@uke.uni-hamburg.de RI Schmidt, Nils Ole/D-5696-2014 FU German Research Foundation (DFG) [SE 2052/1-1, Schm 163 1/3-1] FX This work was supported by grants of the German Research Foundation (DFG), grant numbers: SE 2052/1-1 and Schm 163 1/3-1. NR 31 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0939-3889 J9 Z MED PHYS JI Z. Med. Phys. PD MAR PY 2015 VL 25 IS 1 BP 77 EP 85 DI 10.1016/j.zemedi.2014.01.004 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD8HH UT WOS:000351335300010 PM 24636672 ER PT J AU Ramoska, EA Takayesu, JK AF Ramoska, Edward A. Takayesu, James Kimo TI A Reflection on the Measurement of the Burnout Syndrome Reply SO ACADEMIC EMERGENCY MEDICINE LA English DT Letter ID AMERICAN SURGEONS C1 [Ramoska, Edward A.] Drexel Univ, Coll Med, Dept Emergency Med, Philadelphia, PA 19104 USA. [Takayesu, James Kimo] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Ramoska, EA (reprint author), Drexel Univ, Coll Med, Dept Emergency Med, Philadelphia, PA 19104 USA. EM edward.ramoska@drexelmed.edu; jtakayesu@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2015 VL 22 IS 3 SI SI BP 379 EP 379 DI 10.1111/acem.12609 PG 1 WC Emergency Medicine SC Emergency Medicine GA CD3MA UT WOS:000350981500020 PM 25731681 ER PT J AU Beristianos, M Maguen, S Neylan, T Byers, AL AF Beristianos, Matthew Maguen, Shira Neylan, Thomas Byers, Amy L. TI The Association of Traumatic Experiences with Suicidal Ideation in Older Adults SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Beristianos, Matthew; Maguen, Shira; Neylan, Thomas; Byers, Amy L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Beristianos, Matthew; Maguen, Shira; Neylan, Thomas; Byers, Amy L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA EI 14 BP S81 EP S82 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500074 ER PT J AU Byers, AL Lai, A Arean, P Nelson, C Yaffe, K AF Byers, Amy L. Lai, Amy Arean, Patricia Nelson, Craig Yaffe, Kristine TI Mental Health Services Use Across the Lifespan in Adults at High Risk of Suicide SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Byers, Amy L.; Arean, Patricia; Nelson, Craig; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Byers, Amy L.; Lai, Amy; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA NR 29 BP S173 EP S175 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500174 ER PT J AU Cummings, J Lyketsos, CG Tariot, P Peskind, E Nguyen, U Knowles, N Shin, P Siffert, J AF Cummings, Jeffrey Lyketsos, Constantine G. Tariot, Pierre Peskind, Elaine Nguyen, Uyen Knowles, Nadine Shin, Paul Siffert, Joao TI Dextromethorphan/quinidine (AVP-923) Efficacy and Safety for Treatment of Agitation in Persons with Alzheimer's Disease: Results from a Phase 2 Study (NCT01584440) SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Cummings, Jeffrey] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV USA. [Lyketsos, Constantine G.] Johns Hopkins Med, Baltimore, MD USA. [Tariot, Pierre] Banner Alzheimers Inst, Phoenix, AZ USA. [Peskind, Elaine] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Nguyen, Uyen; Knowles, Nadine; Shin, Paul; Siffert, Joao] Avanir Pharmaceut Inc, Aliso Viejo, CA USA. NR 0 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 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA NR 18 BP S164 EP S165 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500163 ER PT J AU Gatchel, JR Bogunovic, O AF Gatchel, Jennifer R. Bogunovic, Olivera TI Substance Disorders in the Elderly: Diagnosis and Treatment Challenges SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Gatchel, Jennifer R.] McLean Hosp, Massachusetts Gen Hosp, Boston, MA USA. [Gatchel, Jennifer R.; Bogunovic, Olivera] McLean Hosp, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA EI 06 BP S74 EP S74 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500066 ER PT J AU Kamat, R Posada, C Vahia, I AF Kamat, Rujvi Posada, Carolina Vahia, Ipsit TI Can Adults with Severe Cognitive Impairment Use Tablet Device (iPad) Applications (Apps)? SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Kamat, Rujvi; Vahia, Ipsit] Univ Calif San Diego, La Jolla, CA 92093 USA. [Posada, Carolina] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 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 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA EI 57 BP S124 EP S124 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500117 ER PT J AU Kasckow, J Cohen, C Rajii, T Hendrie, HC AF Kasckow, John Cohen, Carl Rajii, Tarek Hendrie, Hugh C. TI RECENT ADVANCES IN LATE LIFE SCHIZOPHRENIA RESEARCH SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Kasckow, John] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Kasckow, John] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Cohen, Carl] Suny Downstate Med Ctr, New York, NY USA. [Rajii, Tarek] Univ Toronto, Toronto, ON, Canada. [Hendrie, Hugh C.] Indiana Univ, Sch Med, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA 407 BP S40 EP S41 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500057 ER PT J AU Kasckow, J Waern, M Szanto, K Conwell, Y AF Kasckow, John Waern, Margda Szanto, Katalin Conwell, Yeates TI RECENT RESEARCH IN LATE LIFE SUICIDE SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Kasckow, John; Szanto, Katalin] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Kasckow, John; Szanto, Katalin] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Waern, Margda] Univ Gothenburg, Gothenburgh, Sweden. [Conwell, Yeates] Univ Rochester, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA 108 BP S9 EP S10 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500009 ER PT J AU Levine, K Koenig, AM Leong, SH Benson, A Streim, J Oslin, D AF Levine, Katherine Koenig, Aaron M. Leong, Shirley H. Benson, Amy Streim, Joel Oslin, David TI Benzodiazepine Prescription Patterns for Older Adults in Pennsylvania SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Levine, Katherine; Koenig, Aaron M.; Benson, Amy; Streim, Joel; Oslin, David] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Leong, Shirley H.; Benson, Amy; Streim, Joel; Oslin, David] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA EI 16 BP S83 EP S84 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500076 ER PT J AU Mintzer, J Steinberg, ES Pearson, JL AF Mintzer, Jacobo Steinberg, Ellen S. Pearson, Joseph L. TI ELDER COURTS: A NEW WAY TO PROTECT THE FRAIL ELDERLY POPULATION SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Mintzer, Jacobo] Roper St Francis Healthcare, Charleston, SC USA. [Steinberg, Ellen S.] Charleston Cty Magistrate, Charleston, SC USA. [Pearson, Joseph L.] SC Inst Med & Publ Hlth, Columbia, SC USA. [Mintzer, Jacobo] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA 315 BP S31 EP S31 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500042 ER PT J AU Soonsawat, A Resident, P Ellison, J Ahmed, I AF Soonsawat, Anothai Resident, Psychiatry Ellison, James Ahmed, Iqbal TI Physician with Cognitive Impairment SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Resident, Psychiatry] Harvard South Shore Psychiat Residency Program, Brockton, MA USA. [Resident, Psychiatry] VA Boston Healthcare Syst, Boston, MA USA. [Ellison, James] McLean Hosp, Belmont, MA 02178 USA. [Ahmed, Iqbal] Tripler Army Med Ctr, Honolulu, HI 96859 USA. NR 0 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 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA EI 66 BP S131 EP S132 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500126 ER PT J AU Wilkins, J AF Wilkins, James TI Ethical Considerations Regarding Capacity Assessments for Consent to Sexual Activity in Older Adults with Dementia Living in Residential Care Settings SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 27-30, 2015 CL New Orleans, LA SP Amer Assoc Geriatr Psychiat C1 [Wilkins, James] McLean Hosp, Belmont, MA 02178 USA. [Wilkins, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 23 IS 3 SU S MA EI 45 BP S113 EP S113 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IV UT WOS:000350829500105 ER PT J AU Larvie, M Timerman, D Thum, JA AF Larvie, M. Timerman, D. Thum, J. A. TI Brain Metabolic Abnormalities Associated with Developmental Venous Anomalies SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ANGIOMA; HEMORRHAGE; ADULTS AB BACKGROUND AND PURPOSE: Developmental venous anomalies are the most common intracranial vascular malformation and are typically regarded as inconsequential, especially when small. While there are data regarding the prevalence of MR imaging findings associated with developmental venous anomalies, FDG-PET findings have not been well-characterized. MATERIALS AND METHODS: Clinical information systems were used to retrospectively identify patients with developmental venous anomalies depicted on MR imaging examinations who had also undergone FDG-PET. Both the MR imaging and FDG-PET scans were analyzed to characterize the developmental venous anomalies and associated findings on the structural and functional scans. Qualitative and quantitative assessments were performed, including evaluation of the size of the developmental venous anomaly, associated MR imaging findings, and characterization of the FDG uptake in the region of the developmental venous anomaly. RESULTS: Twenty-five developmental venous anomalies in 22 patients were identified that had been characterized with both MR imaging and FDG-PET, of which 76% (19/25) were associated with significant metabolic abnormality in the adjacent brain parenchyma, most commonly hypometabolism. Patients with moderate and severe hypometabolism were significantly older (moderate: mean age, 65 +/- 7.4 years, P = .001; severe: mean age, 61 +/- 8.9 years, P = .008) than patients with developmental venous aberrancies that did not have abnormal metabolic activity (none: mean age, 29 +/- 14 years). CONCLUSIONS: Most (more than three-quarters) developmental venous anomalies in our series of 25 cases were associated with metabolic abnormality in the adjacent brain parenchyma, often in the absence of any other structural abnormality. Consequently, we suggest that developmental venous anomalies may be better regarded as developmental venous aberrancies. C1 [Larvie, M.] Harvard Univ, Sch Med, Boston, MA USA. [Larvie, M.; Timerman, D.; Thum, J. A.] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. [Larvie, M.; Timerman, D.; Thum, J. A.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Timerman, D.; Thum, J. A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Larvie, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mlarvie@gmail.com FU National Institutes of Health [P01 AG036694-01, 2R01 AG026484-06A1] FX This work was supported in part by the National Institutes of Health (P01 AG036694-01, 2R01 AG026484-06A1). NR 23 TC 3 Z9 3 U1 0 U2 4 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2015 VL 36 IS 3 BP 475 EP 480 DI 10.3174/ajnr.A4172 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CD3PL UT WOS:000350990900014 PM 25477358 ER PT J AU Bateman, BT Huybrechts, KF Fischer, MA Seely, EW Ecker, JL Oberg, AS Franklin, JM Mogun, H Hernandez-Diaz, S AF Bateman, Brian T. Huybrechts, Krista F. Fischer, Michael A. Seely, Ellen W. Ecker, Jeffrey L. Oberg, Anna S. Franklin, Jessica M. Mogun, Helen Hernandez-Diaz, Sonia TI Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE birth defect; drug; epidemiology; hypertension; pregnancy ID ANTIHYPERTENSIVE MEDICATION USE; CARDIOVASCULAR MALFORMATIONS; ACE-INHIBITORS; UNITED-STATES; 1ST TRIMESTER; POPULATION; EXPOSURE; OUTCOMES; WOMEN; THERAPEUTICS AB OBJECTIVE: Chronic hypertension is a common medical condition in pregnancy. The purpose of the study was to examine the association between maternal chronic hypertension and the risk of congenital malformations in the offspring. STUDY DESIGN: We defined a cohort of 878,126 completed pregnancies linked to infant medical records using the Medicaid Analytic Extract. The risk of congenital malformations was compared between normotensive controls and those with treated and untreated chronic hypertension. Confounding was addressed using propensity score matching. RESULTS: After matching, compared with normotensive controls, pregnancies complicated by treated chronic hypertension were at increased risk of congenital malformations (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.2-1.5), as were pregnancies with untreated chronic hypertension (OR 1.2; 95% CI, 1.1-1.3). In our analysis of organ-specific malformations, both treated and untreated chronic hypertension was associated with a significant increase in the risk of cardiac malformations (OR, 1.6; 95% CI, 1.4-1.9 and OR, 1.5; 95% CI, 1.3-1.7, respectively). These associations persisted across a range of sensitivity analyses. CONCLUSION: There is a similar increase in the risk of congenital malformations (particularly cardiac malformations) associated with treated and untreated chronic hypertension that is independent of measured confounders. Studies evaluating the teratogenic potential of antihypertensive medications must control for confounding by indication. Fetuses and neonates of mothers with chronic hypertension should be carefully evaluated for potential malformations, particularly cardiac defects. C1 [Bateman, Brian T.; Huybrechts, Krista F.; Fischer, Michael A.; Franklin, Jessica M.; Mogun, Helen] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Boston, MA 02115 USA. [Seely, Ellen W.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med,Div Endocrinol Diabet & Metabol, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA. [Ecker, Jeffrey L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. [Oberg, Anna S.; Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Bateman, BT (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Boston, MA 02115 USA. EM bbateman@partners.org RI Oberg, Anna/M-7469-2014 OI Oberg, Anna/0000-0001-6638-1895 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [K08HD075831]; National Heart Lung and Blood Institute at the National Institutes of Health [K24HL096141]; Agency for Healthcare Research and Quality [R01HS018533] FX This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, under grant no. K08HD075831 (B.T.B.) and K24 from the National Heart Lung and Blood Institute at the National Institutes of Health under grant no. K24HL096141 (E.W.S.). The Medicaid Analytic eXtract pregnancy cohort was supported by grant R01HS018533 from the Agency for Healthcare Research and Quality (S.H.-D.). NR 29 TC 4 Z9 4 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2015 VL 212 IS 3 AR 337.e1 DI 10.1016/j.ajog.2014.09.031 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CC5DC UT WOS:000350377500020 PM 25265405 ER PT J AU Chang, MS Tuomala, R Rutherford, AE Mutinga, ML Andersson, KL Burman, BE Brown, RS Oken, E Ukomadu, C AF Chang, Matthew S. Tuomala, Ruth Rutherford, Anna E. Mutinga, Muthoka L. Andersson, Karin L. Burman, Blaire E. Brown, Robert S., Jr. Oken, Emily Ukomadu, Chinweike TI Postpartum care for mothers diagnosed with hepatitis B during pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE adherence; compliance; guidelines; prophylaxis ID VIRUS INFECTION; UNITED-STATES; HEPATOCELLULAR-CARCINOMA; COST-EFFECTIVENESS; ANTIVIRAL THERAPY; SAN-FRANCISCO; RISK-FACTORS; POPULATION; MANAGEMENT; WOMEN AB OBJECTIVE: We sought to determine rates of maternal postpartum hepatitis B virus (HBV) follow-up with a HBV specialist and identify factors associated with poor follow-up, as prior research has focused on infant outcomes and not maternal care. STUDY DESIGN: We conducted a retrospective review of data from Partners HealthCare system, the largest health care system in Massachusetts, and identified women with chronic HBV who delivered from 2002 through 2012. RESULTS: We identified 291 women (mean age 31.5 years, 51% Asian) with incident HBV during pregnancy. In all, 47% had postpartum follow-up with a HBV specialist, but only 19% also had appropriate laboratory tests (hepatitis B e antigen [HBeAg], hepatitis B e antibody, HBV DNA, and ALT) within 1 year of their HBV diagnosis. Mothers with HBV follow-up were more likely to have a primary care physician (PCP) within the Partners HealthCare system (66% vs 38%, P < .0001), a positive HBeAg (20% vs 8%, P = .004), and elevated AST values (17% vs 8%, P = .02). On multivariable logistic regression analysis, a mother who had a PCP (odds ratio, 2.50; 95% confidence interval, 1.37-4.59) or positive HBeAg (odds ratio, 4.45; 95% confidence interval, 1.64-12.06) had a greater likelihood of having HBV follow-up. CONCLUSION: Only 19% of HBV-infected mothers met care guidelines 1 year after being diagnosed with HBV. Inadequate postpartum HBV care affects women of all races/ethnicities. Women who had a PCP as well as those who were HBeAg positive were more likely to be referred for postpartum follow-up with a HBV specialist, suggesting that providers might be referring patients when they perceive HBV to be more serious or complex. C1 [Chang, Matthew S.; Rutherford, Anna E.; Mutinga, Muthoka L.; Ukomadu, Chinweike] Brigham & Womens Hosp, Dept Med, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Tuomala, Ruth] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Andersson, Karin L.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Oken, Emily] Harvard Univ, Sch Med, Boston, MA USA. [Oken, Emily] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Burman, Blaire E.] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA USA. [Brown, Robert S., Jr.] Columbia Univ Coll Phys & Surg, Ctr Liver Dis & Transplantat, New York, NY 10032 USA. RP Chang, MS (reprint author), Brigham & Womens Hosp, Dept Med, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA. EM mchang5@partners.org FU Partners HealthCare Patient Care Quality and Safety Center of Expertise Research Grant; Biomedical Research Institute; Brigham andWomen's Hospital Center for Faculty Development and Diversity'sOffice for Research Careers; Eunice Kennedy Shriver National Institute of Child Health and Human Development [K24 HD069408] FX This study was funded in part by a Partners HealthCare Patient Care Quality and Safety Center of Expertise Research Grant and a microgrant from the Biomedical Research Institute and the Brigham andWomen's Hospital Center for Faculty Development and Diversity'sOffice for Research Careers, which had no involvement in any aspect of the study or manuscript. Funding for E.O. was provided by grant number K24 HD069408 (Eunice Kennedy Shriver National Institute of Child Health and Human Development). NR 32 TC 1 Z9 1 U1 0 U2 4 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 MAR PY 2015 VL 212 IS 3 AR 365.e1 DI 10.1016/j.ajog.2014.09.032 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CC5DC UT WOS:000350377500031 PM 25281364 ER PT J AU Yee, LM Kaimal, AJ Houston, KA Wu, E Thiet, MP Nakagawa, S Caughey, AB Firouzian, A Kuppermann, M AF Yee, Lynn M. Kaimal, Anjali J. Houston, Kathryn A. Wu, Erica Thiet, Mari-Paule Nakagawa, Sanae Caughey, Aaron B. Firouzian, Atoosa Kuppermann, Miriam TI Mode of delivery preferences in a diverse population of pregnant women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE mode of delivery; patient preferences; shared decision making; standard gamble; time tradeoff ID PREVIOUS CESAREAN-SECTION; PLANNED VAGINAL BIRTH; DECISION-MAKING; PATIENT PREFERENCES; BREECH PRESENTATION; TRIAL; OUTCOMES; LABOR; WANT; TERM AB OBJECTIVE: The objective of the study was to assess women's preferences for vaginal vs cesarean delivery in 4 contexts: prior cesarean delivery, twins, breech presentation, and absent indication for cesarean. STUDY DESIGN: This was a cross-sectional study of pregnant women at 24-40 weeks' gestation. After assessing stated preferences for vaginal or cesarean delivery, we used the standard gamble metric to measure the strength of these preferences and the time tradeoff metric to determine how women value the potential processes and outcomes associated with these 2 delivery approaches. RESULTS: Among the 240 participants, 90.8% had a stated preference for vaginal delivery. Across the 4 contexts, these women indicated that, on average, they would accept a 59-75% chance of an attempted vaginal birth ending in a cesarean delivery before choosing a planned cesarean delivery, indicating strong preferences for spontaneous, uncomplicated vaginal delivery. Variations in preferences for labor processes emerged. Although uncomplicated labor ending in vaginal birth was assigned mean utilities of 0.993 or higher (on a 0-1 scale, with higher scores indicating more preferred outcomes), the need for oxytocin, antibiotics, or operative vaginal delivery resulted in lower mean scores, comparable with those assigned to uncomplicated cesarean delivery. Substantially lower scores (ranging from 0.432 to 0.598) were obtained for scenarios ending in severe maternal or neonatal morbidity. CONCLUSION: Although most women expressed strong preferences for vaginal delivery, their preferences regarding interventions frequently used to achieve that goal varied. These data underscore the importance of educating patients about the process of labor and delivery to facilitate incorporation of informed patient preferences in shared decision making regarding delivery approach. C1 [Yee, Lynn M.] Northwestern Univ, Dept Obstet & Gynecol, Feinberg Sch Med, Chicago, IL USA. [Kaimal, Anjali J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA. [Kaimal, Anjali J.] Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Kuppermann, Miriam] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Wu, Erica] Univ Calif Irvine, Dept Obstet & Gynecol, Sch Med, Orange, CA 92668 USA. [Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. RP Kuppermann, M (reprint author), Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. EM kuppermannm@obgyn.ucsf.edu FU University of California, San Francisco, Resource Allocation Program; National Center of Excellence in Women's Health; National Center for Research Resources; National Center for Advancing Translational Sciences; National Institutes of Health, through University of California, San Francisco-Clinical; Translational Science Institute [UL1 RR024131]; University of California; San Francisco-Clinical and Translational Science Institute [UL1 TR000004]; Robert Wood Johnson Foundation's Physician Faculty Scholars Program [RWJF-61535] FX This study was supported in part by the University of California, San Francisco, Resource Allocation Program, which is supported by the National Center of Excellence in Women's Health, the National Center for Research Resources, and the National Center for Advancing Translational Sciences, National Institutes of Health, through University of California, San Francisco-Clinical and Translational Science Institute grant UL1 RR024131 and University of California, San Francisco-Clinical and Translational Science Institute grant UL1 TR000004, and the Robert Wood Johnson Foundation's Physician Faculty Scholars Program grant RWJF-61535. NR 28 TC 2 Z9 2 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2015 VL 212 IS 3 AR 377.e1 DI 10.1016/j.ajog.2014.10.029 PG 24 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CC5DC UT WOS:000350377500036 PM 25446662 ER PT J AU Simavli, H Que, CJ Akduman, M Rizzo, JL Tsikata, E De Boer, JF Chen, TC AF Simavli, Huseyin Que, Christian John Akduman, Mustafa Rizzo, Jennifer L. Tsikata, Edem De Boer, Johannes F. Chen, Teresa C. TI Diagnostic Capability of Peripapillary Retinal Thickness in Glaucoma Using 3D Volume Scans SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; NERVE-FIBER LAYER; INNER PLEXIFORM LAYER; FALSE POSITIVES; HEAD PARAMETERS; HIGH-SPEED; DOMAIN; REPRODUCIBILITY; ATROPHY; ABILITY AB PURPOSE: To determine the diagnostic capability of spectral-domain optical coherence tomography (SD OCT) peripapillary retinal thickness (RT) measurements from 3-dimensional (3D) volume scans for primary open-angle glaucoma (POAG). DESIGN: Cross-sectional study. METHODS: SETTING: Institutional. STUDY POPULATION: 156 patients (89 POAG and 67 normal subjects). OBSERVATION PROCEDURES: One eye of each subject was included. SD OCT peripapillary RT values from 3D volume scans were calculated for 4 quadrants of 3 different sized annuli. Peripapillary retinal nerve fiber layer (RNFL) thickness values were also determined. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC) values, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. RESULTS: The top 5 RT AUROCs for all glaucoma patients and for a subset of early glaucoma patients were for the inferior quadrant of outer circumpapillary annulus of circular grid (OCA) 1 (0.959, 0.939), inferior quadrant of OCA2 (0.945, 0.921), superior quadrant of OCA1 (0.890, 0.811), inferior quadrant of OCA3 (0.887, 0.854), and superior quadrant of OCA2 (0.879, 0.807). Smaller RT annuli OCA1 and OCA2 consistently showed better diagnostic performance than the larger RT annulus OCA3. For both RNFL and RT measurements, best AUROC values were found for inferior RT OCA1 and OCA2, followed by inferior and overall RNFL thickness. CONCLUSION: Peripapillary RT measurements from 3D volume scans showed excellent diagnostic performance for detecting both glaucoma and early glaucoma patients. Peripapillary RT values have the same or better diagnostic capability compared to peripapillary RNFL thickness measurements, while also having fewer algorithm errors. (C) 2015 by Elsevier Inc. All rights reserved. C1 [Simavli, Huseyin; Que, Christian John; Akduman, Mustafa; Rizzo, Jennifer L.; Tsikata, Edem; Chen, Teresa C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Glaucoma Serv, Dept Ophthalmol,Sch Med, Boston, MA 02114 USA. [De Boer, Johannes F.] Vrije Univ Amsterdam, Dept Phys & Astron, Amsterdam, Netherlands. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu RI de Boer, Johannes/B-7590-2012; Simavli, Huseyin/K-4404-2016; OI de Boer, Johannes/0000-0003-1253-4950; Simavli, Huseyin/0000-0003-1657-9099 FU National Institutes of Health [UL 1RR 025758] FX Teresa Chen, American Glaucoma Society Mid-Career Award (San Francisco, California), Massachusetts Lions Eye Fund, Harvard Catalyst Grant, National Institutes of Health UL 1RR 025758, Agency for Healthcare Research and Quality, Fidelity Charitable Fund (Harvard University). NR 45 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 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2015 VL 159 IS 3 BP 545 EP 556 DI 10.1016/j.ajo.2014.12.004 PG 12 WC Ophthalmology SC Ophthalmology GA CC1BV UT WOS:000350077100018 PM 25498354 ER PT J AU Liu, YN Simavli, H Que, CJ Rizzo, JL Tsikata, E Maurer, R Chen, TC AF Liu, Yingna Simavli, Huseyin Que, Christian John Rizzo, Jennifer L. Tsikata, Edem Maurer, Rie Chen, Teresa C. TI Patient Characteristics Associated With Artifacts in Spectralis Optical Coherence Tomography Imaging of the Retinal Nerve Fiber Layer in Glaucoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PARAPAPILLARY CHORIORETINAL ATROPHY; THICKNESS MEASUREMENTS; EYES; QUALITY; MYOPIA; VARIABILITY; CHINESE; NUMBER AB PURPOSE: To determine patient factors and eye conditions associated with artifacts in Spectralis optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) scans. DESIGN: Retrospective cross-sectional study. METHODS: The prevalence of 12 artifact types were described in this review of 2313 eye scans from 1188 patients who underwent a complete eye examination with Spectralis OCT scanning during the period of September 2009 to July 2013. The generalized estimating equations model was used to analyze associations between increased artifact prevalence and 10 patient characteristics, which included age, sex, race, visual acuity, refractive error, astigmatism, cataract status, glaucoma staging, visual field reliability, and glaucoma diagnosis. RESULTS: A total of 1070 or 46.3% of the 2313 eye scans had at least 1 artifact. Decentration error was the most common artifact (27.8%), followed by posterior vitreous detachment artifacts (14.4%). Visual acuity of less than 20/40 (P < .0001), presence of moderate to severe cataracts (P < .0001), advanced stage of glaucoma (P < .0001), and a diagnosis of open-angle glaucoma (P = .0003) were associated with increased prevalence of artifacts. CONCLUSIONS: Clinicians should first assess scans for artifacts before making therapeutic decisions based on RNFL thickness measurements. (C) 2015 by Elsevier Inc. All rights reserved. C1 [Liu, Yingna; Simavli, Huseyin; Que, Christian John; Tsikata, Edem; Maurer, Rie; Chen, Teresa C.] Harvard Univ, Sch Med, Boston, MA USA. [Simavli, Huseyin; Que, Christian John; Rizzo, Jennifer L.; Tsikata, Edem; Chen, Teresa C.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Maurer, Rie] Brigham & Womens Hosp, Ctr Clin Invest, Boston, MA 02115 USA. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM Teresa_Chen@meei.harvard.edu RI Simavli, Huseyin/K-4404-2016; OI Simavli, Huseyin/0000-0003-1657-9099 FU Agency for Healthcare Research and Quality (AHRQ); National Institutes of Health [UL1 RR 025758]; Massachusetts Lions Eye Research Fund; Fidelity Charitable Fund (Harvard University); American Glaucoma Society Mid-Career Award (San Francisco, California); Scientific and Technological Research Council of Turkey FX Teresa C. Chen has received funding from the Agency for Healthcare Research and Quality (AHRQ), National Institutes of Health UL1 RR 025758, Massachusetts Lions Eye Research Fund, Fidelity Charitable Fund (Harvard University), and the American Glaucoma Society Mid-Career Award (San Francisco, California). Huseyin Simavli has received funding from the Scientific and Technological Research Council of Turkey Grant. NR 40 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 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2015 VL 159 IS 3 BP 565 EP 576 DI 10.1016/j.ajo.2014.12.006 PG 12 WC Ophthalmology SC Ophthalmology GA CC1BV UT WOS:000350077100020 PM 25498118 ER PT J AU Ge, RB Wang, ZW Bechis, SK Otsetov, AG Hua, SY Wu, SL Wu, CL Tabatabaei, SH Olumi, AF AF Ge, Rongbin Wang, Zongwei Bechis, Seth K. Otsetov, Alexander G. Hua, Shengyu Wu, Shulin Wu, Chin-Lee Tabatabaei, Shahin Olumi, Aria F. TI DNA Methyl Transferase 1 Reduces Expression of SRD5A2 in the Aging Adult Prostate SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MAMMALIAN DEVELOPMENT; RHEUMATOID-ARTHRITIS; HYPERPLASIA; INFLAMMATION; FINASTERIDE; CANCER; AGE; METHYLTRANSFERASES; DISEASE; MEN AB 5-alpha Reductase type 2 (SRD5A2) is a critical enzyme for prostatic development and growth. Inhibition of SRD5A2 by finasteride is used commonly for the management of urinary obstruction caused by benign prostatic hyperplasia. Contrary to common belief, we have found that expression of SRD5A2 is variable and absent in one third of benign adult prostates. In human samples, absent SRD5A2 expression is associated with hypermethylation of the SRD5A2 promoter, and in vitro SRD5A2 promoter activity is suppressed by methylation. We show that methylation of SRD5A2 is regulated by DNA methyltransferase 1, and inflammatory mediators such as tumor necrosis factor alpha, NF-kappa B, and IL-6 regulate DNA methyltransferase 1 expression and thereby affect SRD5A2 promoter methylation and gene expression. Furthermore, we show that increasing age in mice and humans is associated with increased methylation of the SRD5A2 promoter and concomitantly decreased protein expression. Artificial induction of inflammation in prostate primary epithelial cells leads to hypermethylation of the SRD5A2 promoter and silencing of SRD5A2, whereas inhibition with tumor necrosis factor a inhibitor reactivates SRD5A2 expression. Therefore, expression of SRD5A2 is not static and ubiquitous in benign adult prostate tissues. Methylation and expression of SRD5A2 may be used as a gene signature to tailor therapies for more effective treatment of prostatic diseases. C1 [Ge, Rongbin; Wang, Zongwei; Bechis, Seth K.; Otsetov, Alexander G.; Hua, Shengyu; Wu, Shulin; Wu, Chin-Lee; Tabatabaei, Shahin; Olumi, Aria F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Hua, Shengyu] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Wu, Shulin; Wu, Chin-Lee] Tianjin Univ Tradit Chinese Med, Tianjin, Peoples R China. RP Olumi, AF (reprint author), Massachusetts Gen Hosp, Yawkey Bldg,Ste 7E, Boston, MA 02114 USA. EM olumi.aria@mgh.harvard.edu FU NIH/National Institute for Diabetes and Digestive and Kidney Diseases [NIH/R01 DK091353] FX Supported by the NIH/National Institute for Diabetes and Digestive and Kidney Diseases (NIH/R01 DK091353). NR 43 TC 7 Z9 7 U1 0 U2 2 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 MAR PY 2015 VL 185 IS 3 BP 870 EP 882 DI 10.1016/j.ajpath.2014.11.020 PG 13 WC Pathology SC Pathology GA CD0SI UT WOS:000350783800026 PM 25700986 ER PT J AU Ingmanson, EJ May-Benson, TA Bauman, ML AF Ingmanson, Ellen J. May-Benson, Teresa A. Bauman, Margaret L. TI Behavioral comparisons with peers for a young adult female chimpanzee (Pan troglodytes) following application of sensory integration therapy SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 84th Annual Meeting of the American-Association-of-Physical-Anthropologists CY MAR 25-28, 2015 CL St Louis, MO SP Amer Assoc Phys Anthropologists C1 [Ingmanson, Ellen J.] Bridgewater State Univ, Anthropol, Bridgewater, MA USA. [May-Benson, Teresa A.] Spiral Fdn, Res, Newton, MA USA. [Bauman, Margaret L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol, 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 0002-9483 EI 1096-8644 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD MAR PY 2015 VL 156 SU 60 SI SI BP 175 EP 175 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA CC8CE UT WOS:000350594901196 ER PT J AU Blevins, JE Graham, JL Morton, GJ Bales, KL Schwartz, MW Baskin, DG Havel, PJ AF Blevins, James E. Graham, James L. Morton, Gregory J. Bales, Karen L. Schwartz, Michael W. Baskin, Denis G. Havel, Peter J. TI Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE obesity; food intake; energy expenditure; oxytocin ID SUGAR-SWEETENED BEVERAGES; PARAVENTRICULAR NUCLEUS; INSULIN-RESISTANCE; METABOLIC SYNDROME; VISCERAL ADIPOSITY; RECEPTOR AGONIST; GENE-EXPRESSION; DEFICIENT MICE; ONSET OBESITY; NEURONS AB Despite compelling evidence that oxytocin (OT) is effective in reducing body weight (BW) in diet-induced obese (DIO) rodents, studies of the effects of OT in humans and rhesus monkeys have primarily focused on noningestive behaviors. The goal of this study was to translate findings in DIO rodents to a preclinical translational model of DIO. We tested the hypothesis that increased OT signaling would reduce BW in DIO rhesus monkeys by inhibiting food intake and increasing energy expenditure (EE). Male DIO rhesus monkeys from the California National Primate Research Center were adapted to a 12-h fast and maintained on chow and a daily 15% fructose-sweetened beverage. Monkeys received 2 x daily subcutaneous vehicle injections over 1 wk. We subsequently identified doses of OT (0.2 and 0.4 mg/kg) that reduced food intake and BW in the absence of nausea or diarrhea. Chronic administration of OT for 4 wk (0.2 mg/kg for 2 wk; 0.4 mg/kg for 2 wk) reduced BW relative to vehicle by 3.3 +/- 0.4% (approximate to 0.6 kg; P < 0.05). Moreover, the low dose of OT suppressed 12-h chow intake by 26 +/- 7% (P < 0.05). The higher dose of OT reduced 12-h chow intake by 27 +/- 5% (P < 0.05) and 8-h fructose-sweetened beverage intake by 18 +/- 8% (P < 0.05). OT increased EE during the dark cycle by 14 +/- 3% (P < 0.05) and was associated with elevations of free fatty acids and glycerol and reductions in triglycerides suggesting increased lipolysis. Together, these data suggest that OT reduces BW in DIO rhesus monkeys through decreased food intake as well as increased EE and lipolysis. C1 [Blevins, James E.; Baskin, Denis G.] Dept Vet Affairs Med Ctr, Med Res Serv, Off Res & Dev, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Blevins, James E.; Morton, Gregory J.; Schwartz, Michael W.; Baskin, Denis G.] Univ Washington, Med Ctr, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Morton, Gregory J.; Schwartz, Michael W.] Univ Washington, Sch Med, Diabet & Obes Ctr Excellence, Seattle, WA USA. [Graham, James L.; Havel, Peter J.] Univ Calif Davis, Sch Vet Med, Dept Nutr, Davis, CA 95616 USA. [Graham, James L.; Havel, Peter J.] Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA. [Bales, Karen L.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. RP Blevins, JE (reprint author), VA Puget Sound Hlth Care Syst, Res 151,1660 South Columbian Way, Seattle, WA 98108 USA. EM jeblevin@u.washington.edu FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA); California National Primate Research Center (CNPRC) Pilot Award [0D011107]; Department of VA Merit Review Research Program; National Institutes of Health [DK-095980, HL-091333, HL-107256]; University of California Office of the President; VA Senior Research Career Scientist award FX This material is based upon work supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA). The research in our laboratory has been supported by the California National Primate Research Center (CNPRC) Pilot Award (core grant no. 0D011107) and the Department of VA Merit Review Research Program. The research program of P. J. Havel also receives research support from National Institutes of Health grants DK-095980, HL-091333, HL-107256, HL-107256, and a Multi-campus grant from the University of California Office of the President. D. G. Baskin is the recipient of a VA Senior Research Career Scientist award. NR 72 TC 21 Z9 21 U1 3 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAR 1 PY 2015 VL 308 IS 5 BP R431 EP R438 DI 10.1152/ajpregu.00441.2014 PG 8 WC Physiology SC Physiology GA CD1EC UT WOS:000350816100010 PM 25540103 ER PT J AU Mehtsun, WT Patel, MS Markmann, JF Hertl, M Vagefi, PA AF Mehtsun, Winta T. Patel, Madhukar S. Markmann, James F. Hertl, Martin Vagefi, Parsia A. TI Obstructive jaundice caused by a giant non-parasitic hepatic cyst SO ANNALS OF HEPATOLOGY LA English DT Editorial Material ID LIVER C1 [Mehtsun, Winta T.; Patel, Madhukar S.; Markmann, James F.; Hertl, Martin; Vagefi, Parsia A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplantat Surg, Boston, MA USA. RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, 55 Fruit St,White 544b, Boston, MA 02114 USA. EM pvagefi@partners.org NR 7 TC 0 Z9 0 U1 0 U2 3 PU MEXICAN ASSOC HEPATOLOGY PI MEXICO PA PUNTE DE PIEDRA 150, COLONIA TORIELLO GUERRA, MEXICO, DF CP 14040, MEXICO SN 1665-2681 J9 ANN HEPATOL JI Ann. Hepatol. PD MAR-APR PY 2015 VL 14 IS 2 BP 267 EP 269 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CD2JL UT WOS:000350903500015 PM 25671837 ER PT J AU Kuroki, LM Mangano, M Allsworth, JE Menias, CO Massad, LS Powell, MA Mutch, DG Thaker, PH AF Kuroki, L. M. Mangano, M. Allsworth, J. E. Menias, C. O. Massad, L. S. Powell, M. A. Mutch, D. G. Thaker, P. H. TI Pre-operative Assessment of Muscle Mass to Predict Surgical Complications and Prognosis in Patients With Endometrial Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SARCOPENIC OBESITY; WEIGHT-LOSS; POSTOPERATIVE COMPLICATIONS; MICROSATELLITE INSTABILITY; HOSPITAL ADMISSION; BODY-COMPOSITION; INCREASED LENGTH; BASIC INDICATOR; RISK; CHEMOTHERAPY AB Background. Sarcopenia or loss of skeletal muscle mass is an objective measure of frailty associated with functional impairment and disability. This study aimed to examine the impact of sarcopenia on surgical complications and survival outcomes in patients with endometrial cancer. Methods. A retrospective review of endometrial cancer patients who underwent surgery between 2005 and 2009 was performed. Sarcopenia was assessed on preoperative computed tomography (CT) scan by measurement of the lumbar psoas muscle cross-sectional area and defined as any value below the median (< 4.33 cm(2)). Sarcopenic obesity was defined as sarcopenia plus a body mass index (BMI) of 30 kg/m(2) or higher. Microsatellite instability (MSI) was analyzed using the National Cancer Institute (NCI) consensus markers and tumor from hysterectomy specimens. Results. Of 122 patients, 27 (22 %) met the criteria for sarcopenic obesity. Sarcopenic patients were older than patients with normal muscle mass (mean age, 69.7 vs. 62.1 years; p< 0.001), had a lower BMI (31.1 vs. 39.4 kg/m(2); p< 0.001), and had more comorbidities (p = 0.048). Sarcopenia was not associated with tumor MSI, hospital stay, 90-day readmission rate, or early/late complications. Patients with sarcopenia had a shorter recurrence-free survival than nonsarcopenic patients (median 23.5 vs. 32.1 months; log-rank p = 0.02), but did not differ in terms of overall survival (log-rank p = 0.25). After adjustment for race, BMI, lymphocyte count, and tumor histology, sarcopenia was associated with a fourfold shorter recurrence-free survival (adjusted hazard ratio [HRadj], 3.99; 95 % confidence interval [CI], 1.42-11.3). Conclusions. Sarcopenia has an impact on recurrence-free survival, but does not appear to have a negative impact on surgical outcomes or overall survival among endometrial cancer patients who undergo preoperative CT scan. C1 [Kuroki, L. M.; Massad, L. S.; Powell, M. A.; Mutch, D. G.; Thaker, P. H.] Washington Univ Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, St Louis, MO 63130 USA. [Kuroki, L. M.; Massad, L. S.; Powell, M. A.; Mutch, D. G.; Thaker, P. H.] Alvin J Siteman Canc Ctr, St Louis, MO USA. [Mangano, M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mangano, M.] Harvard Univ, Sch Med, Boston, MA USA. [Allsworth, J. E.] Univ Missouri Kansas City Sch Med, Dept Biomed & Hlth Informat, Kansas City, MO USA. [Menias, C. O.] Mayo Clin, Dept Radiol, Scottsdale, AZ USA. RP Kuroki, LM (reprint author), Washington Univ Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, St Louis, MO 63130 USA. EM kurokil@wudosis.wustl.edu FU NCI Cancer Center [P30 CA91842] FX The Siteman Cancer Center is supported by NCI Cancer Center Support Grant P30 CA91842. NR 27 TC 14 Z9 15 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2015 VL 22 IS 3 BP 972 EP 979 DI 10.1245/s10434-014-4040-8 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA CC7MX UT WOS:000350553100042 PM 25190123 ER PT J AU Englum, BR Saha-Chaudhuri, P Shahian, DM O'Brien, SM Brennan, JM Edwards, FH Peterson, ED AF Englum, Brian R. Saha-Chaudhuri, Paramita Shahian, David M. O'Brien, Sean M. Brennan, J. Matthew Edwards, Fred H. Peterson, Eric D. TI The Impact of High-Risk Cases on Hospitals' Risk-Adjusted Coronary Artery Bypass Grafting Mortality Rankings SO ANNALS OF THORACIC SURGERY LA English DT Article ID NEW-YORK-STATE; ADULT CARDIAC-SURGERY; SHORT-TERM MORTALITY; SURGICAL MORTALITY; CARDIOTHORACIC SURGEONS; QUALITY MEASUREMENT; CLINICAL-OUTCOMES; PERFORMANCE; CARE; DATABASE AB Background. Risk-adjusted mortality (RAM) models are increasingly used to evaluate hospital performance, but the validity of the RAM method has been questioned. Providers are concerned that these methods might not adequately account for the highest levels of risk and that treating high-risk cases will have a negative impact on RAM rankings. Methods. Using cases of isolated coronary artery bypass grafting (CABG) performed at 1002 sites in the United States participating in The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database from 2008 to 2010 (N = 494,955), the STS CABG RAM model performance in high-risk patients was assessed. The ratios of observed to expected (O/E) perioperative mortality were compared among groups of hospitals with varying expected risks. Finally, RAM rates during the overall study period for each site were compared with its performance in a simulated "nightmare year" in which the site's highest risk cases over a 3-year period were concentrated into a 1-year period of exceptional risk. Results. The average predicted mortality for center risk groups ranged from 1.46% for the lowest risk quintile to 2.87% for the highest. The O/E ratios for center risk quintiles 1 to 5 during the overall period were 1.01 (95% confidence interval, 0.96% to 1.06%), 1.00 (0.95% to 1.04%), 0.98 (0.94% to 1.03%), 0.97 (0.93% to 1.01%), and 0.80 (0.77% to 0.84%), respectively. The sites' risk-adjusted mortality rates were not increased when the centers' highest risk cases were concentrated into a single "nightmare year." Conclusions. Our results show that the current riskadjusted models accurately estimate CABG mortality and that hospitals accepting more high-risk CABG patients have equal or better outcomes than do those with predominately lower-risk patients. (C) 2015 by The Society of Thoracic Surgeons C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27705 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Univ Florida, Shands Hosp, Jacksonville, FL USA. RP Peterson, ED (reprint author), Duke Clin Res Inst, 2400 Pratt St,Ste 7009,North Pavill DUMC, Durham, NC 27705 USA. EM eric.peterson@dm.duke.edu OI Saha Chaudhuri, Paramita/0000-0003-1987-320X FU NHLBI [5U01HL-107023] FX This research was partially supported by grant 5U01HL-107023 from the NHLBI. All authors are paid or volunteer staff of the STS or the Duke Clinical Research Institute (analytic center for the STS-ACSD). NR 33 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2015 VL 99 IS 3 BP 856 EP 863 DI 10.1016/j.athoracsur.2014.09.048 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CC7TH UT WOS:000350570800028 PM 25583462 ER PT J AU Kuang, SY Wang, ZH Huang, T Wei, LN Xi, TF Kindy, M Gao, BZ AF Kuang, Serena Y. Wang, Zhonghai Huang, Ting Wei, Lina Xi, Tingfei Kindy, Mark Gao, Bruce Z. TI Prolonging life in chick forebrain-neuron culture and acquiring spontaneous spiking activity on a microelectrode array SO BIOTECHNOLOGY LETTERS LA English DT Article DE Biosensor; Chick forebrain neuron; Lifespan; Microelectrode array; Spontaneous spiking activity ID EMBRYO; HEALTH AB Various types of animal neurons were cultured on a microelectrode array (MEA) platform to form biosensors to detect potential environmental neurotoxins. For a large-scale screening tool, rodent MEA-based cortical-neuron biosensors would be very costly but chick forebrain neurons (FBNs) are abundant, cost-effective, and easy to dissect. However, chick FBNs have a lifespan of similar to 14 days in vitro and their spontaneous spike activity (SSA) has been difficult to develop and detect. We used a high-density neuron-glia co-culture on an MEA to prolong chick FBN lifetime to 3 months with lifetime-long SSA. A remarkable embryonic age-dependency in the culture's morphology, lifespan, and most features of SSA signal was discovered. Our results show the feasibility of developing a chick FBN-MEA biosensor and also establish a new electrophysiological platform for functional study of an in vitro neuronal network. C1 [Kuang, Serena Y.; Wang, Zhonghai; Kindy, Mark; Gao, Bruce Z.] Clemson Univ, Dept Bioengn, Clemson, SC 29634 USA. [Huang, Ting; Wei, Lina; Xi, Tingfei] Peking Univ, Acad Adv Interdisciplinary Studies, Ctr Biomed Mat & Tissue Engn, Beijing 100871, Peoples R China. [Kindy, Mark] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29466 USA. [Kindy, Mark] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29466 USA. [Gao, Bruce Z.] Ralph H Johnson VA Med Ctr, Charleston, SC 29403 USA. RP Gao, BZ (reprint author), Clemson Univ, Dept Bioengn, 201-5 Rhodes Res Hall, Clemson, SC 29634 USA. EM zgao@clemson.edu FU National Institutes of Health through SC COBRE [P20RR021949]; National Natural Science Foundation of China [31070847, 31370956]; Strategic New Industry Development Special Foundation of Shenzhen [JCYJ20130402172114948] FX This work was partially supported by funding from the National Institutes of Health through SC COBRE (P20RR021949), the National Natural Science Foundation of China (Nos. 31070847 and 31370956), and the Strategic New Industry Development Special Foundation of Shenzhen (No. JCYJ20130402172114948). Serena Y. Kuang designed the study, did most of the forebrain tissue dissection, cell culturing, MEA recording, data processing tasks, and wrote the manuscript. Zhonghai Wang was responsible for MEA technical support and programmed the MatLab-based software (NeuroMEA) for MEA data processing. Ting Huang translated all MEA data processing requirements into a flowchart with programming logic that oriented the development of the NeuroMEA software. Lina Wei contributed to chick forebrain and spinal cord dissection and some MEA recordings. Mark Kindy served as a senior researcher in this study and modified the manuscript. As PIs of the Project, Drs. Tingfei Xi and Bruce Z. Gao supervised the overall experimental design and data interpretation and modified and finalized the manuscript. NR 17 TC 3 Z9 3 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-5492 EI 1573-6776 J9 BIOTECHNOL LETT JI Biotechnol. Lett. PD MAR PY 2015 VL 37 IS 3 BP 499 EP 509 DI 10.1007/s10529-014-1704-1 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CC5JL UT WOS:000350394800003 PM 25344105 ER PT J AU Sylvia, LG Shelton, RC Kemp, DE Bernstein, EE Friedman, ES Brody, BD McElroy, SL Singh, V Tohen, M Bowden, CL Ketter, TA Deckersbach, T Thase, ME Reilly-Harrington, NA Nierenberg, AA Rabideau, DJ Kinrys, G Kocsis, JH Bobo, WV Kamali, M McInnis, MG Calabrese, JR AF Sylvia, Louisa G. Shelton, Richard C. Kemp, David E. Bernstein, Emily E. Friedman, Edward S. Brody, Benjamin D. McElroy, Susan L. Singh, Vivek Tohen, Mauricio Bowden, Charles L. Ketter, Terence A. Deckersbach, Thilo Thase, Michael E. Reilly-Harrington, Noreen A. Nierenberg, Andrew A. Rabideau, Dustin J. Kinrys, Gustavo Kocsis, James H. Bobo, William V. Kamali, Masoud McInnis, Melvin G. Calabrese, Joseph R. TI Medical burden in bipolar disorder: findings from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE) SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; medical comorbidity; metabolic syndrome; mood symptoms ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; I-DISORDER; METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; SYMPTOMS SCALE; UNITED-STATES; FOLLOW-UP; PREVALENCE; COMORBIDITY AB ObjectivesIndividuals with bipolar disorder have high rates of other medical comorbidity, which is associated with higher mortality rates and worse course of illness. The present study examined common predictors of medical comorbidity. MethodsThe Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE) enrolled 482 participants with bipolar I or bipolar II disorder in a six-month, randomized comparative effectiveness trial. Baseline assessments included current and lifetime DSM-IV-TR diagnoses, demographic information, psychiatric and medical history, severity of psychiatric symptoms, level of functioning, and a fasting blood draw. Medical comorbidities were categorized into two groups: cardiometabolic (e.g., diabetes, hyperlipidemia, and metabolic syndrome) and non-cardiovascular (e.g., seizures, asthma, and cancer). Additionally, we looked at comorbid substance use (e.g., smoking and drug dependence). ResultsWe found that 96.3% of participants had at least one other medical comorbidity. Older age predicted a greater likelihood of having a cardiometabolic condition. Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition, but a greater chance of having other types of medical comorbidity. Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed, less time spent manic/hypomanic, and longer duration of illness. Medications associated with weight gain were associated with low high-density lipoprotein and abnormal triglycerides. ConclusionsThere appears to be a substantial medical burden associated with bipolar disorder, highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients. C1 [Sylvia, Louisa G.; Bernstein, Emily E.; Deckersbach, Thilo; Reilly-Harrington, Noreen A.; Nierenberg, Andrew A.; Rabideau, Dustin J.; Kinrys, Gustavo] Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, Boston, MA 02114 USA. [Sylvia, Louisa G.; Bernstein, Emily E.; Deckersbach, Thilo; Reilly-Harrington, Noreen A.; Nierenberg, Andrew A.; Rabideau, Dustin J.; Kinrys, Gustavo] Massachusetts Gen Hosp, Dept Psychiat, Res Program, Boston, MA 02114 USA. [Shelton, Richard C.] Univ Alabama Birmingham, Dept Psychiat, Birmingham, AL USA. [Kemp, David E.; Calabrese, Joseph R.] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. [Friedman, Edward S.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. [Brody, Benjamin D.; Kocsis, James H.] Cornell Univ, Dept Psychiat, Weill Cornell Med Coll, New York, NY 10021 USA. [McElroy, Susan L.] Univ Cincinnati, Coll Med, Dept Psychiat, Lindner Ctr HOPE, Cincinnati, OH 45221 USA. [Singh, Vivek; Bowden, Charles L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Tohen, Mauricio] Univ New Mexico, Sch Med, Dept Psychiat, Albuquerque, NM 87131 USA. [Ketter, Terence A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bobo, William V.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. [Kamali, Masoud; McInnis, Melvin G.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Sylvia, LG (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM lsylvia2@partners.org OI Bernstein, Emily/0000-0001-8609-3153 FU Agency for Healthcare Research Quality [R01 HS019371-01] FX This study was funded by the Agency for Healthcare Research & Quality Grant R01 HS019371-01. NR 59 TC 15 Z9 15 U1 5 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2015 VL 17 IS 2 BP 212 EP 223 DI 10.1111/bdi.12243 PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CD2KI UT WOS:000350906500010 PM 25130321 ER PT J AU Hong, SZ Banks, WA AF Hong, Suzi Banks, William A. TI Role of the immune system in HIV-associated neuroinflammation and neurocognitive implications SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Review DE Blood brain barrier; Cognition; HIV; Inflammation; Microglia; NeuroAIDS; Neuroinflammation; Virus ID BLOOD-BRAIN-BARRIER; HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; RECONSTITUTION INFLAMMATORY SYNDROME; COMBINATION ANTIRETROVIRAL THERAPY; POLYMERASE-CHAIN-REACTION; ENHANCED TRANSCELLULAR TRANSPORT; MICROVASCULAR ENDOTHELIAL-CELLS; CHEMOKINE RECEPTOR EXPRESSION; CNS PENETRATION-EFFECTIVENESS AB Individuals living with HIV who are optimally treated with combination antiretroviral therapy (cART) can now lead an extended life. In spite of this remarkable survival benefit from viral suppression achieved by cART in peripheral blood, the rate of mild to moderate cognitive impairment remains high. A cognitive decline that includes impairments in attention, learning and executive function is accompanied by increased rates of mood disorders that together adversely impact the daily life of those with chronic HIV infection. The evidence is clear that cells in the brain are infected with HIV that has crossed the blood brain barrier both as cell-free virus and within infected monocytes and T cells. Viral proteins that circulate in blood can induce brain endothelial cells to release cytokines, invoking another source of neuroinflammation. The difficulty of efficient delivery of cART to the central nervous system (CNS) contributes to elevated viral load in the CNS, resulting in a persistent HIV-associated neurocognitive disorders (HAND). The pathogenesis of HAND is multifaceted, and mounting evidence indicates that immune cells play a major role. HIV-infected monocytes and T cells not only infect brain resident cells upon migration into the CNS but also produce proinflammatory cytokines such as TNF and IL-1 beta, which in turn, further activate microglia and astrocytes. These activated brain resident cells, along with perivascular macrophages, are the main contributors to neuroinflammation in HIV infection and release neurotoxic factors such as excitatory amino acids and inflammatory mediators, resulting in neuronal dysfunction and death. Cytokines, which are elevated in the blood of patients with HIV infection, may also contribute to brain inflammation by entering the brain from the blood. Host factors such as aging and co-morbid conditions such as cytomegalovirus co-infection and vascular pathology are important factors that affect the HIV-host immune interactions in HAND pathogenesis. By these diverse mechanisms, HIV-1 induces a neuro-inflammatory response that is likely to be a major contributor to the cognitive and behavior changes seen in HIV infection. (C) 2014 Elsevier Inc. All rights reserved. C1 [Hong, Suzi] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Banks, William A.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Clin & Educ Ctr, Seattle, WA 98195 USA. [Banks, William A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Hong, SZ (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr MC0804, La Jolla, CA 92093 USA. EM suzihong@ucsd.edu FU NIH [R01HL090975, R01 MH92225, R01AG029834]; VA merit review FX Authors express sincere appreciation to Randy Brooks for his assistance with Fig. 1. Writing of this work was supported in part by the grants R01HL090975 (SH), R01 MH92225 and R01AG029834 (WAB) from the NIH and VA merit review (WAB). NR 168 TC 27 Z9 29 U1 5 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 EI 1090-2139 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD MAR PY 2015 VL 45 BP 1 EP 12 DI 10.1016/j.bbi.2014.10.008 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CC7BX UT WOS:000350523800001 PM 25449672 ER PT J AU Braunstein, LZ Niemierko, A Shenouda, MN Truong, L Sadek, BT Abi Raad, R Wong, JS Punglia, RS Taghian, AG Bellon, JR AF Braunstein, Lior Z. Niemierko, Andrzej Shenouda, Mina N. Linh Truong Sadek, Betro T. Abi Raad, Rita Wong, Julia S. Punglia, Rinaa S. Taghian, Alphonse G. Bellon, Jennifer R. TI Outcome Following Local-Regional Recurrence in Women with Early-Stage Breast Cancer: Impact of Biologic Subtype SO BREAST JOURNAL LA English DT Article DE biologic subtype; breast cancer; local-regional recurrence; salvage therapy; triple-negative breast cancer ID SURGICAL ADJUVANT BREAST; CONSERVING THERAPY; TUMOR RECURRENCE; LOCOREGIONAL RECURRENCES; RANDOMIZED-TRIALS; PROGNOSIS; MASTECTOMY; SURGERY; TIME; RADIOTHERAPY AB Local-regional recurrence (LRR) after breast-conserving therapy (BCT) can result in distant metastasis and decreased disease-free survival (DFS). This study examines factors associated with DFS following LRR. The initial population included 2,233 consecutive women who underwent BCT from 1998 to 2007. Biologic subtype was approximated using a combination of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. Cumulative incidence of DFS after LRR was calculated. The association of clinical, pathologic, and treatment parameters with DFS was evaluated using a Cox regression model. At a median follow-up of 105months, 82 patients (3.7%) had a LRR. Of these, 66 (80%) were in-breast and 16 (20%) involved the ipsilateral lymph nodes. Twenty patients subsequently developed distant metastases. Five-year DFS after initial recurrence was 69.6% for the overall cohort. On univariate analysis, triple-negative disease (ER/PR/HER2 negative, TNBC) was associated with reduced DFS (HR=3.8; 95% CI: 1.8-8.1; p<0.001). Other factors associated with reduced DFS were larger tumor size (HR=1.3; 95% CI: 1.03-1.6; p=0.02), shorter interval from initial diagnosis to LRR (HR=0.98 per month; 95% CI: 0.97-0.99; p=0.02), and no salvage surgery (HR=0.2; 95% CI: 0.09-0.5; p=0.001). On multivariate analysis, TNBC remained the most significant factor associated with reduced DFS (HR=4.8; 95% CI: 2.25-10.4; p<0.001). Compared to women with luminal A disease, those with TNBC had significantly worse DFS (37.5% versus 88.3% at 5years; p<0.001). Women with TNBC who developed LRR were at high risk of subsequent recurrence. Efforts should be targeted toward both preventing initial recurrence and decreasing subsequent metastasis. C1 [Braunstein, Lior Z.] Harvard Radiat Oncol Program, Boston, MA USA. [Niemierko, Andrzej; Shenouda, Mina N.; Sadek, Betro T.; Abi Raad, Rita; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Linh Truong; Wong, Julia S.; Punglia, Rinaa S.; Bellon, Jennifer R.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Linh Truong; Wong, Julia S.; Punglia, Rinaa S.; Bellon, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bellon, JR (reprint author), Brigham & Womens Hosp, ASB 1 Radiat Oncol L2,75 Francis St, Boston, MA 02115 USA. EM jbellon@lroc.harvard.edu NR 23 TC 5 Z9 5 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X EI 1524-4741 J9 BREAST J JI Breast J. PD MAR-APR PY 2015 VL 21 IS 2 BP 161 EP 167 DI 10.1111/tbj.12371 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CD3LY UT WOS:000350981200008 PM 25559656 ER PT J AU Stuart, RK Cripe, LD Maris, MB Cooper, MA Stone, RM Dakhil, SR Turturro, F Stock, W Mason, J Shami, PJ Strickland, SA Costa, LJ Borthakur, G Michelson, GC Fox, JA Leavitt, RD Ravandi, F AF Stuart, Robert K. Cripe, Larry D. Maris, Michael B. Cooper, Maureen A. Stone, Richard M. Dakhil, Shaker R. Turturro, Francesco Stock, Wendy Mason, James Shami, Paul J. Strickland, Stephen A. Costa, Luciano J. Borthakur, Gautam Michelson, Glenn C. Fox, Judith A. Leavitt, Richard D. Ravandi, Farhad TI REVEAL-1, a phase 2 dose regimen optimization study of vosaroxin in older poor-risk patients with previously untreated acute myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE vosaroxin; topoisomerase-II inhibitor; acute myeloid leukaemia; elderly; newly diagnosed ID INTENSIVE CHEMOTHERAPY; FORMERLY SNS-595; VORELOXIN; AGE; DECITABINE; CYTARABINE; OUTCOMES; MODELS; TRIALS AB This phase 2 study (N=116) evaluated single-agent vosaroxin, a first-in-class anticancer quinolone derivative, in patients 60years of age with previously untreated unfavourable prognosis acute myeloid leukaemia. Dose regimen optimization was explored in sequential cohorts (A: 72mg/m(2)d 1, 8, 15; B: 72mg/m(2)d 1, 8; C: 72mg/m(2) or 90mg/m(2)d 1, 4). The primary endpoint was combined complete remission rate (complete remission [CR] plus CR with incomplete platelet recovery [CRp]). Common (>20%) grade 3 adverse events were thrombocytopenia, febrile neutropenia, anaemia, neutropenia, sepsis, pneumonia, stomatitis and hypokalaemia. Overall CR and CR/CRp rates were 29% and 32%; median overall survival (OS) was 70months; 1-year OS was 34%. Schedule C (72mg/m(2)) had the most favourable safety and efficacy profile, with faster haematological recovery (median 27d) and lowest incidence of aggregate sepsis (24%) and 30-d (7%) and 60-d (17%) all-cause mortality; at this dose and schedule, CR and CR/CRp rates were 31% and 35%, median OS was 77months and 1-year OS was 38%. Overall, vosaroxin resulted in low early mortality and an encouraging response rate; vosaroxin 72mg/m(2)d 1, 4 is recommended for further study in this population. Registered at : #NCT00607997. C1 [Stuart, Robert K.; Costa, Luciano J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Cripe, Larry D.] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. [Maris, Michael B.] Rocky Mt Blood & Marrow Transplant Program, Denver, CO USA. [Cooper, Maureen A.] St Francis Hosp, Indianapolis, IN USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dakhil, Shaker R.] Canc Ctr Kansas, Wichita, KS USA. [Turturro, Francesco] Louisiana State Univ, Hlth Sci Ctr, Feist Weiller Canc Ctr, Shreveport, LA 71105 USA. [Stock, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Mason, James] Scripps Canc Ctr, La Jolla, CA USA. [Shami, Paul J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Strickland, Stephen A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Borthakur, Gautam; Ravandi, Farhad] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Michelson, Glenn C.; Fox, Judith A.] Sunesis Pharmaceut Inc, San Francisco, CA USA. [Leavitt, Richard D.] PharmaPacific Inc, Woodside, CA USA. RP Stuart, RK (reprint author), Med Univ S Carolina, 173 Ashley Ave,BSB Suite 104,MSC 635, Charleston, SC 29425 USA. EM stuartrk@musc.edu OI Strickland, Stephen/0000-0002-6861-2041 FU Sunesis Pharmaceuticals FX The authors thank Daniel L. Combs for performing PK analyses and David Arnold for statistical programming. The authors also thank Anna Lau, PhD, and Janis M. B. Leonoudakis, PhD, of Powered 4 Significance LLC for providing editorial assistance on the manuscript. Funding for manuscript development was provided by Sunesis Pharmaceuticals. NR 21 TC 13 Z9 14 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 MAR PY 2015 VL 168 IS 6 BP 796 EP 805 DI 10.1111/bjh.13214 PG 10 WC Hematology SC Hematology GA CD4HN UT WOS:000351043400003 PM 25403830 ER PT J AU Foss, F Advani, R Duvic, M Hymes, KB Intragumtornchai, T Lekhakula, A Shpilberg, O Lerner, A Belt, RJ Jacobsen, ED Laurent, G Ben-Yehuda, D Beylot-Barry, M Hillen, U Knoblauch, P Bhat, G Chawla, S Allen, LF Pohlman, B AF Foss, Francine Advani, Ranjana Duvic, Madeleine Hymes, Kenneth B. Intragumtornchai, Tanin Lekhakula, Arnuparp Shpilberg, Ofer Lerner, Adam Belt, Robert J. Jacobsen, Eric D. Laurent, Guy Ben-Yehuda, Dina Beylot-Barry, Marie Hillen, Uwe Knoblauch, Poul Bhat, Gajanan Chawla, Shanta Allen, Lee F. Pohlman, Brad TI A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE belinostat; histone deacetylase inhibitors; T cell lymphoma; mycosis fungoides; peripheral T cell Lymphoma ID HISTONE DEACETYLASE INHIBITOR; NON-HODGKINS-LYMPHOMAS; RESPONSE CRITERIA; CLINICAL-TRIAL; SOLID TUMORS; CLASSIFICATION; VORINOSTAT; MULTICENTER; CARBOPLATIN; BEXAROTENE AB Belinostat is a pan-histone deacetylase inhibitor with antitumour and anti-angiogenic properties. An open label, multicentre study was conducted in patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who failed 1 prior systemic therapy and were treated with belinostat (1000mg/m(2) intravenously x5d of a 21-d cycle). The primary endpoint was objective response rate (ORR). Patients with PTCL (n=24) had received a median of three prior systemic therapies (range 1-9) and 40% had stage IV disease. Patients with CTCL (n=29) had received a median of one prior skin-directed therapy (range 0-4) and four prior systemic therapies (range 1-9); 55% had stage IV disease. The ORRs were 25% (PTCL) and 14% (CTCL). Treatment-related adverse events occurred in 77% of patients; nausea (43%), vomiting (21%), infusion site pain (13%) and dizziness (11%) had the highest incidence. Treatment-related serious adverse events were Grade 5 ventricular fibrillation; Grade 4 thrombocytopenia; Grade 3 peripheral oedema, apraxia, paralytic ileus and pneumonitis; and Grade 2 jugular vein thrombosis. Belinostat monotherapy was well tolerated and efficacious in patients with recurrent/refractory PTCL and CTCL. This trial was registered at as NCT00274651. C1 [Foss, Francine] Yale Canc Ctr, New Haven, CT 06520 USA. [Advani, Ranjana] Stanford Univ, Stanford, CA 94305 USA. [Duvic, Madeleine] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hymes, Kenneth B.] NYU, Inst Canc, New York, NY USA. [Intragumtornchai, Tanin] Chulalongkorn Hosp, Dept Med, Bangkok, Thailand. [Lekhakula, Arnuparp] Songlanagarind Hosp, Dept Med, Songkhla, Thailand. [Shpilberg, Ofer] Tel Aviv Univ, Beilinson Hosp, Rabin Med Ctr, Haematol,Davidoff Canc Ctr, Petah Tiqwa, Israel. [Shpilberg, Ofer] Tel Aviv Univ, Sackler Sch Med, Petah Tiqwa, Israel. [Lerner, Adam] Boston Med Ctr, Boston, MA USA. [Belt, Robert J.] Kansas City Canc Ctr, Kansas City, MO USA. [Jacobsen, Eric D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Laurent, Guy] Hop Purpan, Toulouse, France. [Ben-Yehuda, Dina] Hadassah Hebrew Univ, Med Ctr, Div Haematol, Jerusalem, Israel. [Beylot-Barry, Marie] Univ Bordeaux, Hop Haut Leveque, Pessac, France. [Hillen, Uwe] Univ Klinikum Essen, Essen, Germany. [Knoblauch, Poul] Topotarget, Copenhagen, Denmark. [Bhat, Gajanan; Chawla, Shanta; Allen, Lee F.] Spectrum Pharmaceut, Irvine, CA USA. [Pohlman, Brad] Cleveland Clin, Hematol Oncol & Blood Disorders, Taussig Canc Inst, Cleveland, OH 44106 USA. RP Foss, F (reprint author), Yale Canc Ctr, POB 208021,333 Cedar St,WWW-403, New Haven, CT 06520 USA. EM francine.foss@yale.edu FU Allos Therapeutics (Spectrum Pharmaceuticals, Inc.) FX KBH is a consultant for Celgene. MD received research support from Allos Therapeutics (a wholly-owned subsidiary of Spectrum Pharmaceuticals, Inc.). LFA, GB and SC are employees of Spectrum Pharmaceuticals. PK is an employee of Topotarget. The remaining authors declare no competing financial interests. NR 30 TC 41 Z9 42 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 MAR PY 2015 VL 168 IS 6 BP 811 EP 819 DI 10.1111/bjh.13222 PG 9 WC Hematology SC Hematology GA CD4HN UT WOS:000351043400005 PM 25404094 ER PT J AU Wei, YY Wang, ZX Su, L Chen, F Tejera, P Bajwa, EK Wurfel, MM Lin, XH Christiani, DC AF Wei, Yongyue Wang, Zhaoxi Su, Li Chen, Feng Tejera, Paula Bajwa, Ednan K. Wurfel, Mark M. Lin, Xihong Christiani, David C. TI Platelet Count Mediates the Contribution of a Genetic Variant in LRRC16A to ARDS Risk SO CHEST LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; ACTIN-BINDING-PROTEIN; CLINICAL-TRIAL APPLICATIONS; ASSOCIATION; PREVALENCE; EXPRESSION; PROGNOSIS; ALI/ARDS; OUTCOMES AB BACKGROUND: Platelets are believed to be critical in pulmonary-origin ARDS as mediators of endothelial damage through their interactions with fibrinogen and multiple signal transduction pathways. A prior meta-analysis identified five loci for platelet count (PLT): BAD, LRRC16A, CD36, JMJD1C, and SLMO2. This study aims to validate the quantitative trait loci (QTLs) of PLT within BAD, LRRC16A, CD36, JMJD1C, and SLMO2 among critically ill patients and to investigate the associations of these QTLs with ARDS risk that may be mediated through PLT. METHODS: ARDS cases and at-risk control subjects were recruited from the intensive care unit of the Massachusetts General Hospital. Exome-wide genotyping data of 629 ARDS cases and 1,026 at-risk control subjects and genome-wide gene expression profiles of 18 at-risk control subjects were generated for analysis. RESULTS: Single-nucleotide polymorphism (SNP) rs7766874 within LRRC16A was a significant locus for PLT among at-risk control subjects (beta - -13.00; 95% CI, -23.22 to -2.77; P - .013). This association was validated using LRRC16A gene expression data from at-risk control subjects (beta = 77.03 per 1 SD increase of log(2) -transformed expression; 95% CI, 27.26-126.80; P = .005). Further, rs7766874 was associated with ARDS risk conditioned on PLT (OR = 0.68; 95% CI, 0.51-0.90; P = .007), interacting with PLT (OR = 1.15 per effect allele per 100 X 10(3)/mu L of PLT; 95% CI, 1.03-1.30; P = .015), and mediated through PLT (indirect OR = 1.045; 95% CI, 1.007-1.085; P = .021). CONCLUSIONS: Our findings support the role of LRRC16A in platelet formation and suggest the importance of LRRC16A in ARDS pathophysiology by interacting with, and being mediated through, platelets. C1 [Wei, Yongyue; Wang, Zhaoxi; Su, Li; Tejera, Paula; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Bajwa, Ednan K.; Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Wurfel, Mark M.] Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. [Wei, Yongyue; Chen, Feng] Nanjing Med Univ, Sch Publ Hlth, Key Lab Modern Toxicol, Dept Epidemiol & Biostat,Minist Educ, Nanjing, Jiangsu, Peoples R China. RP Christiani, DC (reprint author), Bldg 1,Room 1401,665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Heart, Lung, and Blood Institute [R01HL060710]; National Natural Science Foundation of China [81402764, 81473070]; Natural Science Foundation of Jiangsu, China [BK20140907] FX This work was supported by the National Heart, Lung, and Blood Institute [Grant R01HL060710 to Dr Christiani], the National Natural Science Foundation of China [Grant 81402764 to Dr Wei, Grant 81473070 to Dr Chen], and the Natural Science Foundation of Jiangsu, China [Grant BK20140907 to Dr Wei]. NR 52 TC 5 Z9 5 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2015 VL 147 IS 3 BP 607 EP 617 DI 10.1378/chest.14-1246 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CC5RC UT WOS:000350419200039 PM 25254322 ER PT J AU Buman, MP Kline, CE Youngstedt, SD Phillips, B de Mello, MT Hirshkowitz, M AF Buman, Matthew P. Kline, Christopher E. Youngstedt, Shawn D. Phillips, Barbara de Mello, Marco Tulio Hirshkowitz, Max TI Sitting and Television Viewing Novel Risk Factors for Sleep Disturbance and Apnea Risk? Results from the 2013 National Sleep Foundation Sleep in America Poll SO CHEST LA English DT Article ID ACTIVITY QUESTIONNAIRE IPAQ; SEDENTARY BEHAVIORS; CARDIOVASCULAR-DISEASE; EXERCISE; MORTALITY; QUALITY; HEALTH; ADULTS; METAANALYSIS; DURATION AB BACKGROUND: Excess sitting is emerging as a novel risk factor for cardiovascular disease, diabetes, mental illness, and all-cause mortality. Physical activity, distinct from sitting, is associated with better sleep and lower risk for OSA, yet relationships among sitting behaviors and sleep/OSA remain unknown. We examined whether total sitting time and sitting while viewing television were associated with sleep duration and quality, OSA risk, and sleepiness. METHODS: The 2013 National Sleep Foundation Sleep in America Poll was a cross-sectional study of 1,000 adults aged 23 to 60 years. Total sitting time, time watching television while sitting, sleep duration and quality, OSA risk, and daytime sleepiness were assessed. RESULTS: After adjusting for confounding factors (including BMI and physical activity), each additional hour per day of total sitting was associated with greater odds of poor sleep quality (OR [95% CI] = 1.06 [1.01, 1.11]) but not with other sleep metrics (including sleep duration), OSA risk, or daytime sleepiness. For television viewing while sitting, each additional hour per day was associated with greater odds of long sleep onset latency (>= 30 min) (OR = 1.15 [1.04, 1.27]), waking up too early in the morning (OR = 1.12 [1.03, 1.23]), poor sleep quality (OR = 1.12 [1.02, 1.24]), and "high risk" for OSA (OR = 1.15 [1.04, 1.28]). Based upon an interaction analysis, regular physical activity was protective against OSA risk associated with television viewing (P = .04). CONCLUSIONS: Excess sitting was associated with relatively poor sleep quality. Sitting while watching television was associated with relatively poor sleep quality and OSA risk and may be an important risk factor for sleep disturbance and apnea risk. C1 [Buman, Matthew P.; Youngstedt, Shawn D.] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ 85004 USA. [Kline, Christopher E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Youngstedt, Shawn D.] Arizona State Univ, Phoenix VA Hlth Care Syst, Coll Nursing & Hlth Innovat, Phoenix, AZ 85004 USA. [Phillips, Barbara] Univ Kentucky, Coll Med, Div Pulm Crit Care & Sleep Med, Lexington, KY USA. [de Mello, Marco Tulio] Univ Fed Sao Paulo, Dept Psicobiol, Sao Paulo, Brazil. [Hirshkowitz, Max] Baylor Coll Med, Sleep Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Hirshkowitz, Max] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Buman, MP (reprint author), Arizona State Univ, Sch Nutr & Hlth Promot, 500 N 3rd St,Mail Code 3020, Phoenix, AZ 85004 USA. EM matthew.buman@asu.edu RI Kline, Christopher/B-1477-2012; de Mello, Marco Tulio/G-3237-2010 OI Kline, Christopher/0000-0003-1025-9430; de Mello, Marco Tulio/0000-0003-3896-2208 FU National Sleep Foundation; National Institutes of Health [K23HL118318, R01HL095799] FX This study was funded by the National Sleep Foundation and by the National Institutes of Health [Grants K23HL118318 to Dr Kline and R01HL095799 to Dr Youngstedt]. NR 38 TC 4 Z9 4 U1 2 U2 8 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2015 VL 147 IS 3 BP 728 EP 734 DI 10.1378/chest.14-1187 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CC5RC UT WOS:000350419200051 PM 25633255 ER PT J AU Tapias, LF Lanuti, M AF Tapias, Luis F. Lanuti, Michael TI Tapias Score for Predicting Recurrences in Resected Solitary Fibrous Tumor of the Pleura Controversial Points and Future Perspectives Emerging From an External Validation Response SO CHEST LA English DT Letter ID SYSTEM C1 [Tapias, Luis F.; Lanuti, Michael] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Lanuti, M (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM mlanuti@mgh.harvard.edu NR 4 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 MAR PY 2015 VL 147 IS 3 BP E116 EP E117 DI 10.1378/chest.14-2892 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CC5RC UT WOS:000350419200018 PM 25732462 ER PT J AU Joynt, KE Mega, JL O'Donoghue, ML AF Joynt, Karen E. Mega, Jessica L. O'Donoghue, Michelle L. TI Difference or Disparity Will Big Data Improve Our Understanding of Sex and Cardiovascular Disease? SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE healthcare disparities; quality of healthcare ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; GENDER-DIFFERENCES; CLINICAL-OUTCOMES; ARTERY-DISEASE; WOMEN; MORTALITY; MEN; RISK; METAANALYSIS C1 [Joynt, Karen E.; Mega, Jessica L.; O'Donoghue, Michelle L.] Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, Boston, MA 20015 USA. [Mega, Jessica L.; O'Donoghue, Michelle L.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 20015 USA. Harvard Univ, Sch Med, Boston, MA USA. [Joynt, Karen E.] US Dept HHS, Off Assistant Secretary Planning & Evaluat, Washington, DC 20201 USA. RP Joynt, KE (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA USA. EM kjoynt@partners.org NR 39 TC 5 Z9 5 U1 2 U2 12 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 MAR PY 2015 VL 8 IS 2 SU 1 BP S52 EP S55 DI 10.1161/CIRCOUTCOMES.115.001701 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CD0MK UT WOS:000350767800008 PM 25714822 ER PT J AU De Berardinis, B Gaggin, HK Magrini, L Belcher, A Zancla, B Femia, A Simon, M Motiwala, S Bhardwaj, A Parry, BA Nagurney, JT Coudriou, C Legrand, M Sadoune, M Di Somma, S Januzzi, JL AF De Berardinis, Benedetta Gaggin, Hanna K. Magrini, Laura Belcher, Arianna Zancla, Benedetta Femia, Alexandra Simon, Mandy Motiwala, Shweta Bhardwaj, Anju Parry, Blair A. Nagurney, John T. Coudriou, Charles Legrand, Matthieu Sadoune, Malha Di Somma, Salvatore Januzzi, James L., Jr. CA Global Res Acute Conditions Team G TI Comparison between admission natriuretic peptides, NGAL and sST2 testing for the prediction of worsening renal function in patients with acutely decompensated heart failure SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE B-type natriuretic peptides (BNP); cardiorenal syndrome; neutrophil gelatinase associated lipocalin (NGAL); worsening renal function ID GELATINASE-ASSOCIATED LIPOCALIN; QUALITY INITIATIVE ADQI; ACUTE KIDNEY INJURY; 11TH CONSENSUS CONFERENCE; CARDIORENAL SYNDROME; SERUM CREATININE; OUTCOMES; ST2; DEFINITION; RISK AB Background: In order to predict the occurrence of worsening renal function (WRF) and of WRF plus in-hospital death, 101 emergency department (ED) patients with acute decompensated heart failure (ADHF) were evaluated with testing for amino-terminal pro-B-type natriuretic peptide (NT-proBNP), BNP, sST2, and neutrophil gelatinase associated lipocalin (NGAL). Methods: In a prospective international study, biomarkers were collected at the time of admission; the occurrence of subsequent in hospital WRF was evaluated. Results: In total 26% of patients developed WRF. Compared to patients without WRF, those with WRF had a longer inhospital length of stay (LOS) (mean LOS 13.1 +/- 13.4 days vs. 4.8 +/- 3.7 days, p<0.001) and higher in- hospital mortality [6/26 (23%) vs. 2/75 (2.6%), p<0.001]. Among the biomarkers assessed, baseline NT- proBNP (4846 vs. 3024 pg/mL; p=0.04), BNP (609 vs. 435 pg/mL; p=0.05) and NGAL (234 vs. 174 pg/mL; p=0.05) were each higher in those who developed WRF. In logistic regression, the combination of elevated natriuretic peptide and NGAL were additively predictive for WRF (ORNT-proBNP+NGAL = 2.79; ORBNP+NGAL=3.11; both p<0.04). Rates of WRF were considerably higher in patients with elevation of both classes of biomarker. Comparable results were observed in a separate cohort of 162 patients with ADHF from a different center. Conclusions: In ED patients with ADHF, the combination of NT- proBNP or BNP plus NGAL at presentation may be useful to predict impending WRF. C1 [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gaggin, Hanna K.; Belcher, Arianna; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Bhardwaj, Anju; Januzzi, James L., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. [De Berardinis, Benedetta; Magrini, Laura; Zancla, Benedetta; Di Somma, Salvatore] Univ Roma La Sapienza, St Andrea Hosp, Dept Med Surg Sci & Translat Med, Emergency Med, I-00185 Rome, Italy. [Parry, Blair A.; Nagurney, John T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Coudriou, Charles; Legrand, Matthieu] GH St Louis Lariboisiere, AP HP, Dept Anesthesiol & Crit Care & Burn Unit, Paris, France. [Legrand, Matthieu] Univ Paris Diderot, Lariboisiere Hosp, INSERM, F-75475 Paris, France. [Sadoune, Malha] Lariboisiere Hosp, INSERM, UMR INSERM 942, Paris, France. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Yawkey 5984 32 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Alere; Nanosphere; Thermo Fisher; Roche Diagnostics; Critical Diagnostics; BG Medicine; Siemens FX Dr. Nagurney has received grant support from Alere, Nanosphere, and Thermo Fisher. Dr. Di Somma has received grant support from Alere. Dr. Januzzi has received grant support from Roche Diagnostics, Critical Diagnostics, BG Medicine, Thermo Fisher, and Siemens. The other authors have no conflicts to report. NR 29 TC 7 Z9 7 U1 1 U2 7 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 EI 1437-4331 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAR PY 2015 VL 53 IS 4 BP 613 EP 621 DI 10.1515/cclm-2014-0191 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CC9FU UT WOS:000350674500023 PM 25473804 ER PT J AU Richter, JM Campbell, EJ Chung, DC AF Richter, James M. Campbell, Emily J. Chung, Daniel C. TI Interval Colorectal Cancer After Colonoscopy SO CLINICAL COLORECTAL CANCER LA English DT Article DE Cancer screening; Colorectal cancer; Colonoscopy; Interval cancer; Quality ID SCREENING COLONOSCOPY; NEGATIVE COLONOSCOPY; MISS-RATE; POPULATION; SURVEILLANCE; QUALITY; RISK; COLON; PREDICTORS; PREVENTION AB Interval colon cancers represent a small but important subgroup of colon cancers. Although some might occur in part because of genetic predisposition others are due to other risk factors such as age, history of neoplasia, and limitations in the examination. Understanding these predisposing characteristics might allow customized or improved screening or surveillance strategies. Background: As more patients are screened for colorectal cancer a small but significant number of interval cancers develop after colonoscopy for colorectal cancer screening. Materials and Methods: We reviewed records of 75,314 adult patients who underwent colonoscopy for screening or diagnostic purposes between 1998 and 2006 inclusively, and identified 77 who developed interval cancers within the next 5 years. We reviewed their original endoscopic findings to determine the clinical and endoscopic factors that might predict a greater risk for future cancers. Results: Patients aged >= 60 years had a higher risk of an interval neoplasm (P < .0001). Interval cancers were more common on the right side of the colon and in the hepatic flexure (both P < .0001). We did not observe an increased rate of interval cancers in patients with poor preparation (P = .799); however, examination completion rates did affect the rate of interval cancers (P = .016). Conclusion: Better identification of higher risk patients and assurance of follow-up examinations might increase the percentage of colon cancers discovered at an early stage. Special attention to careful examination of the right colon is key. C1 [Richter, James M.; Campbell, Emily J.; Chung, Daniel C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Richter, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. EM jrichter@mgh.harvard.edu FU Oliver S. and Jennie R. Donaldson Charitable Trust FX This study was funded, in part, by a grant from the Oliver S. and Jennie R. Donaldson Charitable Trust. Wendy Ho, MD, and William Puricelli, BSN, contributed to the data collection and analysis of earlier portions of this study. NR 33 TC 6 Z9 6 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 EI 1938-0674 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD MAR PY 2015 VL 14 IS 1 BP 46 EP 51 DI 10.1016/j.clcc.2014.11.001 PG 6 WC Oncology SC Oncology GA CC7FW UT WOS:000350534100008 PM 25510180 ER PT J AU Goff, SL Eneanya, ND Feinberg, R Germain, MJ Marr, L Berzoff, J Cohen, LM Unruh, M AF Goff, Sarah L. Eneanya, Nwamaka D. Feinberg, Rebecca Germain, Michael J. Marr, Lisa Berzoff, Joan Cohen, Lewis M. Unruh, Mark TI Advance Care Planning: A Qualitative Study of Dialysis Patients and Families SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; PALLIATIVE CARE; OF-LIFE; DECISION-MAKING; RENAL-DISEASE; CKD; END; COMMUNICATION; DISPARITIES; ESRD AB Background and objectives More than 90,000 patients with ESRD die annually in the United States, yet advance care planning (ACP) is underutilized. Understanding patients' and families' diverse needs can strengthen systematic efforts to improve ACP. Design, setting, participants, & measurements In-depth interviews were conducted with a purposive sample of patients and family/friends from dialysis units at two study sites. Applying grounded theory, interviews were audiotaped, professionally transcribed, and.analyzed in an iterative process. Emergent themes were identified, discussed, and organized into major themes and subthemes. Results Thirteen patients and nine family/friends participated in interviews. The mean patient age was 63 years (SD 14) and five patients were women. Participants identified as black (n=1), Hispanic (n=4), Native American (n=4), Pacific Islander (n=1), white (n=11), and mixed (n=1). Three major themes with associated subthemes were identified. The first theme, "Prior experiences with ACP," revealed that these discussions rarely occur, yet most patients desire them. A potential role for the primary care physician was broached. The second theme, "Factors that may affect perspectives on ACP," included a desire for more of a connection with the nephrologist, positive and negative experiences with the dialysis team, disenfranchisement, life experiences, personality traits, patient-family/friend relationships, and power differentials. The third theme, "Recommendations for discussing ACP," included thoughts on who should lead discussions, where and when discussions should take place, what should be discussed and how. Conclusions Many participants desired better communication with their nephrologist and/or their dialysis team. A number expressed feelings of disenfranchisement that could negatively impact ACP discussions through diminished trust. Life experiences, personality traits, and relationships with family and friends may affect patient perspectives regarding ACP. This study's findings may inform clinital practice and will be useful in designing prospective intervention studies to improve patient and family experiences at the end of life. C1 [Goff, Sarah L.] Baystate Med Ctr, Dept Internal Med, Div Gen Med, Springfield, MA 01199 USA. [Germain, Michael J.] Baystate Med Ctr, Dept Internal Med, Div Nephrol, Springfield, MA 01199 USA. [Goff, Sarah L.] Baystate Med Ctr, Ctr Qual Care Res, Springfield, MA 01199 USA. [Feinberg, Rebecca; Cohen, Lewis M.] Baystate Med Ctr, Dept Psychiat, Springfield, MA 01199 USA. [Eneanya, Nwamaka D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Internal Med, Boston, MA USA. [Marr, Lisa] Univ New Mexico, Dept Internal Med, Div Geriatr & Palliat Med, Albuquerque, NM 87131 USA. [Unruh, Mark] Univ New Mexico, Dept Internal Med, Div Nephrol, Albuquerque, NM 87131 USA. [Berzoff, Joan] Smith Coll, Sch Social Work, Northampton, MA 01063 USA. RP Goff, SL (reprint author), Baystate Med Ctr, Dept Internal Med, Div Gen Med, 280 Chestnut St, Springfield, MA 01199 USA. EM Sarah.goffmd@baystatehealth.org FU Patient-Centered Outcomes Research Institute (PCORI) Program Award [1304-7360]; National Institute of Diabetes and Digestive and Kidney Diseases [K24-DK094872] FX This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Program Award (1304-7360). All statements in this report, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of the PCORI, its Board of Governors, or the Methodology Committee. N.D.E. was supported in part by a mentorship grant from the National Institute of Diabetes and Digestive and Kidney Diseases (K24-DK094872). NR 48 TC 11 Z9 11 U1 2 U2 18 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 MAR PY 2015 VL 10 IS 3 BP 390 EP 400 DI 10.2215/CJN.07490714 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA CC9QH UT WOS:000350705200009 PM 25680737 ER PT J AU Hall, RK Toles, M Massing, M Jackson, E Peacock-Hinton, S O'Hare, AM Colon-Emeric, C AF Hall, Rasheeda K. Toles, Mark Massing, Mark Jackson, Eric Peacock-Hinton, Sharon O'Hare, Ann M. Colon-Emeric, Cathleen TI Utilization of Acute Care among Patients with ESRD Discharged Home from Skilled Nursing Facilities SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; TRANSITIONAL CARE; HOSPITAL READMISSIONS; CONTROLLED-TRIAL; HEART-FAILURE; DIALYSIS; OUTCOMES; PROGRAM; QUALITY; OLDER AB Background and objectives Older adults with ESRD often receive care in skilled nursing facilities (SNFs) after an acute hospitalization; however, little is known about acute care use after SNF discharge to home. Design, setting, participants, & measurements This study used Medicare claims for North and South Carolina to identify patients with ESRD who were discharged home from a SNF between January 1, 2010 and August 31, 2011. Nursing Home Compare data were used to ascertain SNF characteristics. The primary outcome was time from SNF discharge to first acute care use (hospitalization or emergency department visit) within 30 days. Cox proportional hazards models were used to identify patient and facility characteristics associated with the outcome. Results Among 1223 patients with ESRD discharged home from a SNP after an acute hospitalization, 531 (43%) had at least one rehospitalization or emergency department visit within 30 days. The median time to first acute care use was 37 days. Characteristics associated with a shorter time to acute care use were black race (hazard ratio [HRL 1.25; 95% confidence interval [95% CI], 1.04 to 1.51), dual Medicare-Medicaid coverage (HR, 1.24; 95% CI, 1.03 to 1.50), higher Charlson comorbidity score (HR, 1.07; 95% CI, 1.01 to 1.12), number of hospitalizations during the 90 days before SNF admission (HR, 1.12; 95% CI, 1.03 to 1.22), and index hospital discharge diagnoses of cellulitis, abscess, and/or skin ulcer (HR, 2.59; 95% CI, 1.36 to 4.45). Home health use after SNP discharge was associated with a lower rate of acute care use (HR, 0.72; 95% CI, 0.59 to 0.87). There were no statistically significant associations between SNF characteristics and time to first acute care use. Conclusions Almost one in every two older adults with ESRD discharged home after a post acute SNF stay used acute care services within 30 days of discharge. Strategies to reduce acute care utilization in these patients are needed. C1 [Hall, Rasheeda K.; Colon-Emeric, Cathleen] Durham Vet Affairs Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Hall, Rasheeda K.] Duke Univ, Med Ctr, Dept Med, Div Nephrol, Durham, NC 27710 USA. [Colon-Emeric, Cathleen] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Toles, Mark; Massing, Mark] Univ N Carolina, Chapel Hill, NC USA. [Jackson, Eric; Peacock-Hinton, Sharon] Carolinas Ctr Med Excellence Inc, Cary, NC USA. [O'Hare, Ann M.] Vet Affairs Puget Sound Healthcare Syst, Hosp & Specialty Med, Seattle, WA USA. [O'Hare, Ann M.] Vet Affairs Puget Sound Healthcare Syst, Hlth Serv R&D Ctr Excellence, Seattle, WA USA. [O'Hare, Ann M.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA USA. RP Hall, RK (reprint author), Duke Univ, Med Ctr, Dept Med, Div Nephrol, Box DUMC 2747,2424 Erwin Rd,Suite 605, Durham, NC 27710 USA. EM rasheeda.stephens@duke.edu FU Carolinas Center for Medical Excellence - Centers for Medicare & Medicaid Services, an agency of the U.S. Department of Health and Human Services [500-2011-NC10C, 500-2011-SC10C]; National Institute on Aging of the National Institutes of Health [P30AG028716]; Office of Academic Affiliations, U.S. Department of Veterans Affairs FX This publication is based on analyses performed by The Carolinas Center for Medical Excellence under contract number 500-2011-NC10C (Utilization and Quality Control Peer Review Organization for the State of North Carolina) and contract number 500-2011-SC10C (Utilization and Quality Control Peer Review Organization for the State of South Carolina), funded by the Centers for Medicare & Medicaid Services, an agency of the U.S. Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. The authors assume full responsibility for the accuracy and completeness of the ideas presented.; Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number P30AG028716. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Hall was also supported by the Office of Academic Affiliations, U.S. Department of Veterans Affairs. The content of this manuscript does not reflect the views of the Department of Veterans Affairs. NR 25 TC 7 Z9 7 U1 1 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 MAR PY 2015 VL 10 IS 3 BP 428 EP 434 DI 10.2215/CJN.03510414 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CC9QH UT WOS:000350705200013 PM 25649158 ER PT J AU Honda, JR Knight, V Chan, ED AF Honda, Jennifer R. Knight, Vijaya Chan, Edward D. TI Pathogenesis and Risk Factors for Nontuberculous Mycobacterial Lung Disease SO CLINICS IN CHEST MEDICINE LA English DT Article DE Nontuberculous mycobacteria; Lung disease; Risk factors; Pathogenesis ID RAPIDLY GROWING MYCOBACTERIA; AVIUM COMPLEX; PULMONARY-DISEASE; CLINICAL-FEATURES; TNF-ALPHA; CELL-WALL; ABSCESSUS INFECTION; GLYCOPEPTIDOLIPIDS; INTRACELLULARE; DEFICIENCY AB Nontuberculous mycobacteria (NTM) infections are broadly classified as skin and soft tissue infections, isolated lung disease, and visceral or disseminated disease. The degree of underlying immune abnormalities varies between each classification. Skin and soft tissue infections are usually the result of iatrogenic or accidental inoculation of NTM in otherwise normal hosts. Visceral and disseminated NTM disease invariably occurs in individuals with more severe immunosuppression. Although the focus of this article is to discuss the pathogenesis of NTM lung disease, the risk factors of visceral/disseminated NTM disease are also summarized, as they provide insights into host-defense mechanisms against these organisms. C1 [Honda, Jennifer R.; Chan, Edward D.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Honda, Jennifer R.; Knight, Vijaya; Chan, Edward D.] Natl Jewish Hlth, Dept Med, Cell Biol Program, Denver, CO 80206 USA. [Honda, Jennifer R.; Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Chan, ED (reprint author), Natl Jewish Hlth, 0509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org NR 70 TC 15 Z9 15 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-5231 EI 1557-8216 J9 CLIN CHEST MED JI Clin. Chest Med. PD MAR PY 2015 VL 36 IS 1 BP 1 EP 11 DI 10.1016/j.ccm.2014.10.001 PG 11 WC Respiratory System SC Respiratory System GA CC8IW UT WOS:000350612700003 PM 25676515 ER PT J AU Ghatalia, P Je, YJ El Mouallem, N Nguyen, PL Trinh, QD Sonpavde, G Choueiri, TK AF Ghatalia, Pooja Je, Youjin El Mouallem, Nemer Nguyen, Paul L. Quoc-Dien Trinh Sonpavde, Guru Choueiri, Toni K. TI Hepatotoxicity with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis of randomized clinical trials SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Vascular endothelial growth factor receptor; Tyrosine kinase inhibitors; Approved; Hepatotoxicity; Meta-analysis ID CELL LUNG-CANCER; PHASE-III TRIAL; ADVANCED BREAST-CANCER; METASTATIC COLORECTAL-CANCER; ADVANCED HEPATOCELLULAR-CARCINOMA; MEDULLARY-THYROID CANCER; PLACEBO-CONTROLLED TRIAL; INDUCED LIVER-INJURY; DOUBLE-BLIND; 1ST-LINE TREATMENT AB A meta-analysis of randomized controlled trials (RCT) was conducted to determine the relative risk (RR) of hepatotwdcity with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Citations from PubMed/Medline, abstracts from major conferences, clinicaltrials.gov and package inserts were reviewed to include RCTs comparing arms with or without a VEGFR TKI. The RRs of all-grade ALT, AST, ALP and bilirubin elevation in 18,282 patients from 52 trials were 1.57 (95% CI 1.38-1.79, p < 0.001), 1.57 (95% CI 1.36-1.81, p < 0.001), 1.20 (95% CI 1.09-1.83, p < 0.001) and 1.55 (95% CI 1.21-1.97, p < 0.001) respectively, and high-grade elevations were 1.66(95% CI 1.25-2.20,p = 0.001), 1.61 (95% CI 1.21-2.14, p = 0.001), 1.02(95% CI 0.70-1.47,p = 0.932) and 1.34 (95% CI 1.0-1.81, p = 0.054) respectively compared to those in the non-TKI group. The incidence of hepatic failure with VEGFR TKIs was 0.8%. Published by Elsevier Ireland C1 [Ghatalia, Pooja; El Mouallem, Nemer] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL 35294 USA. [Je, Youjin] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea. [Nguyen, Paul L.; Quoc-Dien Trinh; Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Nguyen, Paul L.; Quoc-Dien Trinh; Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sonpavde, Guru] Univ Alabama Birmingham, Med Ctr, Dept Internal Med, Sect Med Oncol, Birmingham, AL 35294 USA. RP Sonpavde, G (reprint author), Univ Alabama Birmingham, Ctr Comprehens Canc, 1802 6th Ave S,NP2540B, Birmingham, AL 35294 USA. EM gsonpavde@uabmc.edu; toni_choueiri@dfci.harvard.edu FU DF/HCC Kidney Cancer SPORE [P50 CA101942-01]; Trust Family FX This work was supported in part by DF/HCC Kidney Cancer SPORE P50 CA101942-01 to TKC and by the Trust Family, Loker Pinard and the Michael Brigham Funds for Kidney Cancer Research to TKC. NR 78 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 EI 1879-0461 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAR PY 2015 VL 93 IS 3 BP 257 EP 276 DI 10.1016/j.critrevonc.2014.11.006 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA CD0PW UT WOS:000350777400011 PM 25523486 ER PT J AU Davids, MS Alyea, EP AF Davids, Matthew S. Alyea, Edwin P. TI The Evolving Role of Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia SO CURRENT HEMATOLOGIC MALIGNANCY REPORTS LA English DT Article DE Allogeneic transplantation; Stem cell transplantation; Kinase inhibitor; Novel agent; Chemoimmunotherapy; Graft versus host disease ID BONE-MARROW-TRANSPLANTATION; TERM-FOLLOW-UP; GENOMIC ABERRATIONS; YOUNGER PATIENTS; CLL3X TRIAL; SURVIVAL; FLUDARABINE; INHIBITOR; MUTATIONS; THERAPY AB Chronic lymphocytic leukemia (CLL) patients with high-risk markers such as del(17p) or those who have relapsed after multiple lines of therapy have a poor prognosis and allogeneic hematopoietic cell transplantation (alloHCT) has historically been the best opportunity for achieving long-term disease control. Recently, several new highly efficacious and well-tolerated small molecules targeting the B cell receptor (BCR) pathway and Bcl-2 have been approved or are in the late stages of development. These new agents are altering therapeutic paradigms in CLL, but unlike with alloHCT, information on long-term disease control is lacking. Here, we provide an overview of the data supporting the use of HCT in CLL and the promising results with the novel agents. We discuss the evolving role of alloHCT for CLL in the novel agent era, including identifying the patients most likely to benefit from transplantation and optimal transplantation timing, as well the use of novel agents in the post-transplantation setting. C1 [Davids, Matthew S.; Alyea, Edwin P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Matthew_Davids@dfci.harvard.edu; Edwin_Alyea@dfci.harvard.edu FU Infinity; Pharmacyclics; TG Therapeutics; Genentech; Janssen; Gilead FX Dr. Matthew S. Davids reports grants from Infinity, Pharmacyclics, and TG Therapeutics. Dr. Davids reports personal fees from Infinity, TG Therapeutics, Genentech, Janssen, and Gilead. Dr. Edwin P. Alyea reports personal fees from Janssen. NR 51 TC 0 Z9 0 U1 0 U2 1 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1558-8211 EI 1558-822X J9 CURR HEMATOL MALIG R JI Curr. Hematol. Malig. Rep. PD MAR PY 2015 VL 10 IS 1 BP 18 EP 27 DI 10.1007/s11899-014-0247-9 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA CD5BY UT WOS:000351103900003 PM 25682168 ER PT J AU Nolan, CJ Ruderman, NB Kahn, SE Pedersen, O Prentki, M AF Nolan, Christopher J. Ruderman, Neil B. Kahn, Steven E. Pedersen, Oluf Prentki, Marc TI Insulin Resistance as a Physiological Defense Against Metabolic Stress: Implications for the Management of Subsets of Type 2 Diabetes SO DIABETES LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; BLOOD-GLUCOSE CONTROL; ACTIVATED PROTEIN-KINASE; MALONYL-COA; MULTIFACTORIAL INTERVENTION; SUBSTRATE METABOLISM; INTENSIVE INSULIN; TREATED PATIENTS; ACCORD TRIAL; FOLLOW-UP AB Stratifying the management of type 2 diabetes (T2D) has to take into account marked variability in patient phenotype due to heterogeneity in its pathophysiology, different stages of the disease process, and multiple other patient factors including comorbidities. The focus here is on the very challenging subgroup of patients with T2D who are overweight or obese with insulin resistance (IR) and the most refractory hyperglycemia due to an inability to change lifestyle to reverse positive energy balance. For this subgroup of patients with T2D, we question the dogma that IR is primarily harmful to the body and should be counteracted at any cost. Instead we propose that IR, particularly in this high-risk subgroup, is a defense mechanism that protects critical tissues of the cardiovascular system from nutrient-induced injury. Overriding IR in an effort to lower plasma glucose levels, particularly with intensive insulin therapy, could therefore be harmful. Treatments that nutrient off-load to lower glucose are more likely to be beneficial. The concepts of IR as an adaptive defense mechanism and insulin-induced metabolic stress may provide explanation for some of the unexpected outcomes of recent major clinical trials in T2D. Potential molecular mechanisms underlying these concepts; their clinical implications for stratification of T2D management, particularly in overweight and obese patients with difficult glycemic control; and future research requirements are discussed. C1 [Nolan, Christopher J.] Canberra Hosp, Dept Endocrinol, Canberra, ACT, Australia. [Nolan, Christopher J.] Australian Natl Univ, Sch Med, Canberra, ACT, Australia. [Ruderman, Neil B.] Boston Univ, Med Ctr, Diabet Res Unit, Boston, MA USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Prentki, Marc] Univ Montreal, CRCHUM, Quebec City, PQ, Canada. [Prentki, Marc] Univ Montreal, Montreal Diabet Res Ctr, Quebec City, PQ, Canada. [Prentki, Marc] Univ Montreal, Dept Nutr, Quebec City, PQ, Canada. [Prentki, Marc] Univ Montreal, Dept Biochem & Mol Med, Quebec City, PQ, Canada. RP Nolan, CJ (reprint author), Canberra Hosp, Dept Endocrinol, Canberra, ACT, Australia. EM christopher.nolan@anu.edu.au RI Nolan, Christopher/B-2026-2008; OI Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health [R01-DK019514, P01-HL068758, P30-DK017047]; Canadian Institutes of Health Research; National Health and Medical Research Council [1028108]; Department of Veterans Affairs FX Work was supported in part by grants from the National Institutes of Health (R01-DK019514, [N.B.R. and M.P.], P01-HL068758 [N.B.R.], and P30-DK017047 [S.E.K.]), the Canadian Institutes of Health Research (M.P.), the National Health and Medical Research Council (project grant 1028108 [C.J.N.]), and the Department of Veterans Affairs (S.E.K.). NR 73 TC 27 Z9 27 U1 2 U2 18 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 MAR PY 2015 VL 64 IS 3 BP 673 EP 686 DI 10.2337/db14-0694 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CC3GX UT WOS:000350235900003 PM 25713189 ER PT J AU Moon, HS Huh, JY Dincer, F Schneider, BE Hasselgren, PO Mantzoros, CS AF Moon, Hyun-Seuk Huh, Joo Young Dincer, Fadime Schneider, Benjamin E. Hasselgren, Per-Olof Mantzoros, Christos S. TI Identification and Saturable Nature of Signaling Pathways Induced by Metreleptin in Humans: Comparative Evaluation of In Vivo, Ex Vivo, and In Vitro Administration SO DIABETES LA English DT Article ID TYROSINE PHOSPHATASE SHP-2; LEPTIN-REPLACEMENT THERAPY; ACTIVATED PROTEIN-KINASE; METHIONYL HUMAN LEPTIN; FATTY-ACID OXIDATION; INSULIN-RESISTANCE; GENE-EXPRESSION; SKELETAL-MUSCLE; CELLS; MICE AB Signaling pathways activated by leptin in metabolically important organs have largely been studied only in animal and/or cell culture studies. In this study, we examined whether leptin has similar effects in human peripheral tissues in vivo, ex vivo, and in vitro and whether the response would be different in lean and obese humans. For in vivo leptin signaling, metreleptin was administered and muscle, adipose tissue, and peripheral blood mononuclear cells were taken for analysis of signal activation. Experiments were also done ex vivo and with primary cultured cells in vitro. The signal activation was compared between male versus female and obese versus lean humans. Acute in vivo, ex vivo, and/or in vitro metreleptin administration similarly activated STAT3, AMPK, ERK1/2, Akt, mTOR, NF-B, and/or IKK/ without any differences between male versus female and obese versus lean subjects. All signaling pathways were saturable at approximate to 30-50 ng/mL, consistent with the clinical evidence showing no additional effect(s) in obese subjects who already have high levels of leptin. Our data provide novel information on downstream effectors of metreleptin action in humans that may have therapeutic implications. C1 [Moon, Hyun-Seuk; Huh, Joo Young; Dincer, Fadime; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Schneider, Benjamin E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Minimally Invas Surg, Boston, MA 02215 USA. [Hasselgren, Per-Olof] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Moon, Hyun-Seuk/G-8576-2015 OI Moon, Hyun-Seuk/0000-0002-5216-2090 FU National Institutes of Health [DK-081913]; VA Merit award; Beth Israel Deaconess Medical Center FX This work was supported by the National Institutes of Health (DK-081913) and a VA Merit award. The Mantzoros Laboratory is also supported by a discretionary grant from Beth Israel Deaconess Medical Center. Metreleptin was provided through an agreement with the Beth Israel Deaconess Medical Center. NR 45 TC 2 Z9 2 U1 0 U2 2 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 MAR PY 2015 VL 64 IS 3 BP 828 EP 839 DI 10.2337/db14-0625 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CC3GX UT WOS:000350235900024 PM 25249580 ER PT J AU Hamman, RF Horton, E Barrett-Connor, E Bray, GA Christophi, CA Crandall, J Florez, JC Fowler, S Goldberg, R Kahn, SE Knowler, WC Lachin, JM Murphy, MB Venditti, E AF Hamman, Richard F. Horton, Edward Barrett-Connor, Elizabeth Bray, George A. Christophi, Costas A. Crandall, Jill Florez, Jose C. Fowler, Sarah Goldberg, Ronald Kahn, Steven E. Knowler, William C. Lachin, John M. Murphy, Mary Beth Venditti, Elizabeth CA Diabet Prevention Program DPP Res TI Factors Affecting the Decline in Incidence of Diabetes in the Diabetes Prevention Program Outcomes Study (DPPOS) SO DIABETES LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; FOLLOW-UP; WEIGHT-LOSS; FASTING GLUCOSE; PIMA-INDIANS; RISK; MELLITUS; ROSIGLITAZONE; PROGRESSION AB During the first 7 years of the Diabetes Prevention Program Outcomes Study (DPPOS), diabetes incidence rates, when compared with the Diabetes Prevention Program (DPP), decreased in the placebo (-42%) and metformin (-25%), groups compared with the rates in the intensive lifestyle intervention (+31%) group. Participants in the placebo and metformin groups were offered group intensive lifestyle intervention prior to entering the DPPOS. The following two hypotheses were explored to explain the rate differences: effective intervention (changes in weight and other factors due to intensive lifestyle intervention) and exhaustion of susceptible (changes in mean genetic and diabetes risk scores). No combination of behavioral risk factors (weight, physical activity, diet, smoking, and antidepressant or statin use) explained the lower DPPOS rates of diabetes progression in the placebo and metformin groups, whereas weight gain was the factor associated with higher rates of progression in the intensive lifestyle intervention group. Different patterns in the average genetic risk score over time were consistent with exhaustion of susceptibles. Results were consistent with exhaustion of susceptibles for the change in incidence rates, but not the availability of intensive lifestyle intervention to all persons before the beginning of the DPPOS. Thus, effective intervention did not explain the lower diabetes rates in the DPPOS among subjects in the placebo and metformin groups compared with those in the DPP. C1 [Hamman, Richard F.] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO 80045 USA. [Horton, Edward] Joslin Diabet Ctr, Sect Clin Res, Boston, MA 02215 USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Christophi, Costas A.; Fowler, Sarah; Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Crandall, Jill] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldberg, Ronald] Univ Miami, Sch Med, Diabet Res Inst, Miami, FL USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Knowler, William C.] NIDDK, Phoenix, AZ USA. [Murphy, Mary Beth] Univ Tennessee, Ctr Hlth Sci, Div Endocrinol, Memphis, TN 38163 USA. [Venditti, Elizabeth] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr Hlth Syst, Pittsburgh, PA 15213 USA. RP Hamman, RF (reprint author), Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO 80045 USA. EM dppmail@bsc.gwu.edu OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; National Eye Institute; National Heart, Lung, and Blood Institute; Office of Women's Health; National Institute on Minority Health and Health Disparities; Centers for Disease Control and Prevention; Department of Veterans Affairs; American Diabetes Association FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding of the clinical and coordinating centers that designed and undertook the study and collected, managed, analyzed, and interpreted the data. The General Clinical Research Center Program and the National Center for Research Resources supported data collection at many of the clinical centers. The study was funded by the NIDDK as a cooperative agreement The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and by the Indian Health Service. Funding was also provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Institute on Aging; the National Eye Institute; the National Heart, Lung, and Blood Institute; the Office of Women's Health; the National Institute on Minority Health and Health Disparities; the Centers for Disease Control and Prevention; the Department of Veterans Affairs; and the American Diabetes Association. The sponsor of this study was represented on the Steering Committee and played a part in the study design, how the study was performed, and the publication of the article. The funding agency was not represented on the writing group, although all members of the Steering Committee had input into the contents of the report. NR 32 TC 8 Z9 8 U1 0 U2 3 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 MAR PY 2015 VL 64 IS 3 BP 989 EP 998 DI 10.2337/db14-0333 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CC3GX UT WOS:000350235900038 ER PT J AU Zhang, H Hao, Y Manor, B Novak, P Milberg, W Zhang, J Fang, J Novak, V AF Zhang, Hui Hao, Ying Manor, Bradley Novak, Peter Milberg, William Zhang, Jue Fang, Jing Novak, Vera TI Intranasal Insulin Enhanced Resting-State Functional Connectivity of Hippocampal Regions in Type 2 Diabetes SO DIABETES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; COGNITIVE IMPAIRMENT; VERBAL FLUENCY; DISEASE; HUMANS; NETWORK; MEMORY; SENSITIVITY; CORTEX AB Type 2 diabetes mellitus (T2DM) alters brain function and manifests as brain atrophy. Intranasal insulin has emerged as a promising intervention for treatment of cognitive impairment. We evaluated the acute effects of intranasal insulin on resting-state brain functional connectivity in older adults with T2DM. This proof-of-concept, randomized, double-blind, placebo-controlled study evaluated the effects of a single 40 IU dose of insulin or saline in 14 diabetic and 14 control subjects. Resting-state functional connectivity between the hippocampal region and default mode network (DMN) was quantified using functional MRI (fMRI) at 3Tesla. Following insulin administration, diabetic patients demonstrated increased resting-state connectivity between the hippocampal regions and the medial frontal cortex (MFC) as compared with placebo (cluster size: right, P = 0.03) and other DMN regions. On placebo, the diabetes group had lower connectivity between the hippocampal region and the MFC as compared with control subjects (cluster size: right, P = 0.02), but on insulin, MFC connectivity was similar to control subjects. Resting-state connectivity correlated with cognitive performance. A single dose of intranasal insulin increases resting-state functional connectivity between the hippocampal regions and multiple DMN regions in older adults with T2DM. Intranasal insulin administration may modify functional connectivity among brain regions regulating memory and complex cognitive behaviors. C1 [Zhang, Hui; Hao, Ying; Manor, Bradley; Zhang, Jue; Fang, Jing] Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China. [Manor, Bradley] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02115 USA. [Novak, Peter] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. [Milberg, William] VA Boston Healthcare, New England Geriatr Res Educ & Clin Ctr Boston, Boston Div, Boston, MA USA. [Milberg, William] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Zhang, Jue; Fang, Jing] Peking Univ, Coll Engn, Beijing 100871, Peoples R China. [Novak, Vera] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. RP Novak, V (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. EM vnovak@bidmc.harvard.edu OI Zhang, Hui/0000-0001-8313-0756 FU China Scholarship Council [201206010220]; 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) [8KL2-TR-000168-05, 8UL1-TR-000170-05]; Translational Research Center for TBI and Stress Disorders (TRACTS); VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C]; VA Merit Review Award; National Institute of Diabetes and Digestive and Kidney Diseases [5R21-DK-084463-02]; National Institute on Aging [1R01-AG-0287601-A2]; Harvard Catalyst; Harvard University, academic health care centers; National Natural Science Foundation of China [NSFC 11372013] FX Y.H. received grant support from China Scholarship Council (201206010220). B.M. received a KL2 Medical Research Investigator Training award (1KL2RR025757-04) from 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 8KL2-TR-000168-05). W.M. was also supported by the Translational Research Center for TBI and Stress Disorders (TRACTS), the VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C), and VA Merit Review Award to Regina McGlinchey. V.N. has received grants from the National Institute of Diabetes and Digestive and Kidney Diseases (5R21-DK-084463-02) and the National Institute on Aging (1R01-AG-0287601-A2) related to this study, and V.N., B.M., P.N., and W.M. received salaries from these grants. This work was conducted with support from Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health award 8UL1-TR-000170-05, and financial contributions from Harvard University and its affiliated academic health care centers). This work was also supported by the National Natural Science Foundation of China (NSFC 11372013). NR 49 TC 18 Z9 21 U1 1 U2 20 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 MAR PY 2015 VL 64 IS 3 BP 1025 EP 1034 DI 10.2337/db14-1000 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CC3GX UT WOS:000350235900041 PM 25249577 ER PT J AU Marshall, BDL Operario, D Bryant, KJ Cook, RL Edelman, EJ Gaither, JR Gordon, AJ Kahler, CW Maisto, SA McGinnis, KA van den Berg, JJ Zaller, ND Justice, AC Fiellin, DA AF Marshall, Brandon D. L. Operario, Don Bryant, Kendall J. Cook, Robert L. Edelman, E. Jennifer Gaither, Julie R. Gordon, Adam J. Kahler, Christopher W. Maisto, Stephen A. McGinnis, Kathleen A. van den Berg, Jacob J. Zaller, Nickolas D. Justice, Amy C. Fiellin, David A. TI Drinking trajectories among HIV-infected men who have sex with men: A cohort study of United States veterans SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol; Men who have sex with men; Veterans; HIV infection; Trajectories; Trends ID POSTTRAUMATIC-STRESS-DISORDER; ALCOHOL-RELATED PROBLEMS; VA HEALTH-CARE; SUBSTANCE USE; POSITIVE MEN; AUDIT-C; SUPPORTED EMPLOYMENT; INVERSE PROBABILITY; MINORITY VETERANS; BINGE DRINKING AB Background: Although high rates of alcohol consumption and related problems have been observed among HIV-infected men who have sex with men (MSM), little is known about the long-term patterns of and factors associated with hazardous alcohol use in this population. We sought to identify alcohol use trajectories and correlates of hazardous alcohol use among HIV-infected MSM. Methods: Sexually active, HIV-infected MSM participating in the Veterans Aging Cohort Study were eligible for inclusion. Participants were recruited from VA infectious disease clinics in Atlanta, Baltimore, New York, Houston, Los Angeles, Pittsburgh, and Washington, DC. Data from annual self-reported assessments and group-based trajectory models were used to identify distinct alcohol use trajectories over an eight-year study period (2002-2010). We then used generalized estimate equations (GEE) to examine longitudinal correlates of hazardous alcohol use (defined as an AUDIT-C score >= 4). Results: Among 1065 participants, the mean age was 45.5 (SD = 9.2) and 606 (58.2%) were African American. Baseline hazardous alcohol use was reported by 309 (29.3%). Group-based trajectory modeling revealed a distinct group (12.5% of the sample) with consistently hazardous alcohol use, characterized by a mean AUDIT-C score of >5 at every time point. In a GEE-based multivariable model, hazardous alcohol use was associated with earning <$6000 annually, having an alcohol-related diagnosis, using cannabis, and using cocaine. Conclusions: More than 1 in 10 HIV-infected MSM US veterans reported consistent, long-term hazardous alcohol use. Financial insecurity and concurrent substance use were predictors of consistently hazardous alcohol use, and may be modifiable targets for intervention. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Marshall, Brandon D. L.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Operario, Don; Kahler, Christopher W.; van den Berg, Jacob J.] Brown Univ, Sch Publ Hlth, Dept Behav & Social Sci, Providence, RI 02912 USA. [Bryant, Kendall J.] NIAAA, Rockville, MD 20852 USA. [Cook, Robert L.] Univ Florida, Dept Epidemiol, Gainesville, FL 32610 USA. [Edelman, E. Jennifer; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. [Edelman, E. Jennifer; Gaither, Julie R.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Ctr Interdisciplinary Res AIDS, New Haven, CT 06510 USA. [Gaither, Julie R.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15206 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Kahler, Christopher W.] Brown Univ, Sch Publ Hlth, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Kahler, Christopher W.] Brown Univ, Sch Publ Hlth, Alcohol Res Ctr HIV ARCH, Providence, RI 02912 USA. [Maisto, Stephen A.] Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. [Maisto, Stephen A.] Syracuse VA Med Ctr, VA Ctr Integrated Healthcare, Syracuse, NY 13210 USA. [McGinnis, Kathleen A.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [van den Berg, Jacob J.] Miriam Hosp, Div Infect Dis, Providence, RI 02906 USA. [Zaller, Nickolas D.] Univ Arkansas Med Sci, Dept Hlth Behav & Hlth Educ, Little Rock, AR 72205 USA. RP Marshall, BDL (reprint author), Brown Univ, Sch Publ Hlth, Dept Epidemiol, 121 South Main St,Box G-S-121-2, Providence, RI 02912 USA. EM brandon_marshall@brown.edu OI Fiellin, David/0000-0002-4006-010X; Justice, Amy/0000-0003-0139-5502 FU National Institute on Alcohol Abuse and Alcoholism [U24-AA022000, U10-AA013566, U01-AA020795, U01-AA020790, U24-AA020794, P01-AA019072]; National Institute of Allergy and Infectious Diseases [P30-AI042853]; NIAAA [U24-AA022002, K05-AA16928]; National Institute on Drug Abuse [F31-DA035567] FX This work was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA: U24-AA022000, U10-AA013566, U01-AA020795, U01-AA020790, U24-AA020794, U10-AA013566, and P01-AA019072), the National Institute of Allergy and Infectious Diseases (P30-AI042853), and in kind by the U.S. Department of Veterans Affairs. Dr. Robert Cook is supported by the NIAAA (U24-AA022002). Ms. Julie Gaither is supported by the National Institute on Drug Abuse (F31-DA035567). Dr. Stephen Maisto is supported by the NIAAA (K05-AA16928). Dr. E. Jennifer Edelman is a Yale-Drug Abuse, Addiction, and HIV Research Scholar (K12-DA033312). The sponsors had no role in the study design; the collection, analysis and interpretation of data; the writing of the report; and in the decision to submit the article for publication. NR 65 TC 3 Z9 3 U1 4 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 2015 VL 148 BP 69 EP 76 DI 10.1016/j.drugalcdep.2014.12.023 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CC7DF UT WOS:000350527200009 PM 25596785 ER PT J AU Williams, EC Frasco, MA Jacobson, IG Maynard, C Littman, AJ Seelig, AD Crum-Cianflone, NF Nagel, A Boyko, EJ AF Williams, Emily C. Frasco, Melissa A. Jacobson, Isabel G. Maynard, Charles Littman, Alyson J. Seelig, Amber D. Crum-Cianflone, Nancy F. Nagel, Anna Boyko, Edward J. TI Risk factors for relapse to problem drinking among current and former US military personnel: A prospective study of the Millennium Cohort SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Problem drinking; Alcohol use disorders; Millennium Cohort Study; Military; Relapse prospective study; Risk factors ID ALCOHOL-RELATED PROBLEMS; MENTAL-HEALTH PROBLEMS; PRIMARY-CARE; FOLLOW-UP; COMBAT EXPOSURE; SERVICE MEMBERS; BINGE DRINKING; UNITED-STATES; USE DISORDERS; SUBSTANCE USE AB Background: Military service members may be prone to relapse to problem drinking after remission, given a culture of alcohol use as a coping mechanism for stressful or traumatic events associated with military duties or exposures. However, the prevalence and correlates of relapse are unknown. We sought to identify socio-demographic, military, behavioral, and health characteristics associated with relapse among current and former military members with remittent problem drinking. Methods: Participants in the longitudinal Millennium Cohort Study who reported problem drinking at baseline (2001-2003) and were remittent at first follow-up (2004-2006) were included (n = 6909). Logistic regression models identified demographic, military service, behavioral, and health characteristics that predicted relapse (report of >= 1 past-year alcohol-related problem on the validated Patient Health Questionnaire) at the second follow-up (2007-2008). Results: Sixteen percent of those with remittent problem drinking relapsed. Reserve/National Guard members compared with active-duty members (odds ratio [OR] = 1.71,95% confidence interval [CI]: 1.45-2.01), members separated from the military during follow-up (OR= 1.46, 95% CI: 1.16-1.83), and deployers who reported combat exposure (OR = 1.32, 95% CI: 1.07-1.62, relative to non-deployers) were significantly more likely to relapse. Those with multiple deployments were significantly less likely to relapse (OR= 0.73,95% CI: 0.58-0.92). Behavioral factors and mental health conditions also predicted relapse. Conclusion: Relapse was common and associated with military and non-military factors. Targeted intervention to prevent relapse may be indicated for military personnel in particular subgroups, such as Reservists, veterans, and those who deploy with combat exposure. (C) 2015 Published by Elsevier Ireland Ltd. C1 [Williams, Emily C.; Maynard, Charles] Denver Seattle Ctr Innovat Veteran Ctr & Value Dr, Dept Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res Dev, Seattle, WA 98101 USA. [Williams, Emily C.; Maynard, Charles] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Frasco, Melissa A.; Jacobson, Isabel G.; Crum-Cianflone, Nancy F.; Nagel, Anna] Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA 92106 USA. [Maynard, Charles; Littman, Alyson J.; Seelig, Amber D.; Boyko, Edward J.] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Littman, Alyson J.; Boyko, Edward J.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Crum-Cianflone, Nancy F.] Naval Med Ctr San Diego, San Diego, CA 92134 USA. [Boyko, Edward J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM emily.williams3@va.gov; Frasco.Melissa@gmail.com; isabeljacobson@yahoo.com; cmaynard@u.washington.edu; Alyson.Littman@va.gov; Amber.Seelig@va.gov; nancy32red@yahoo.com; anna.nagel@med.navy.mil; Edward.Boyko@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU HSRD VA [IK2 HX001161] NR 71 TC 2 Z9 2 U1 3 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 2015 VL 148 BP 93 EP 101 DI 10.1016/j.drugalcdep.2014.12.031 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CC7DF UT WOS:000350527200012 PM 25599962 ER PT J AU Johri, AM Chitty, DW Hua, LQ Marincheva, G Picard, MH AF Johri, Amer M. Chitty, David W. Hua, Lanqi Marincheva, Gergana Picard, Michael H. TI Assessment of Image Quality in Real Time Three-Dimensional Dobutamine Stress Echocardiography: An Integrated 2D/3D Approach SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE dobutamine; stress test; echocardiography; three-dimensional; integrated protocol; quality ID CLINICAL-APPLICATIONS; MYOCARDIAL-ISCHEMIA; FEASIBILITY; LIMITATIONS AB BackgroundThree-dimensional (3D) stress echocardiography is a relatively new technique offering the potential to acquire images of the entire left ventricle from 1 or 2 transducer positions in a time-efficient manner. Relative to two-dimensional (2D) imaging, the ability to quickly acquire full volume images during peak stress with 3D echocardiography can eliminate left ventricular (LV) foreshortening while reducing inter-operator variability. Our objectives were to (1) determine the practicality of a novel integrated 2D/3D stress protocol in incorporating 3D imaging into a standard 2D stress echocardiogram and (2) to determine whether the quality of imaging using the novel 2D/3D protocol was sufficient for interpretation. MethodsTwenty-five patients referred for stress echocardiography underwent an integrated 2D/3D image acquisition protocol. LV segments were scored from 0 (absent or no clear endocardial visualization) to 3 (excellent/full visualization of endocardial border) with each modality. 2D segment quality scoring was compared with 3D. An integrated score was compared with either 2D or 3D imaging alone. ResultsTwo-dimensional and 3D imaging were optimal for differing segments and the integrated protocol was superior to either modality alone. 3D imaging was superior in visualizing the anterior and anterolateral region of the base segments, compared to 2D imaging. 3D imaging was less useful for the base, the mid-inferior, and the inferoseptal segments, thus emphasizing the need to retain 2D imaging in stress echocardiography at this time. ConclusionThe integrated 2D/3D protocol approach to stress echocardiography is technically feasible and maximizes image quality of dobutamine stress echocardiography, improving patient assessment. C1 [Johri, Amer M.; Chitty, David W.] Queens Univ, Div Cardiol, Kingston, ON, Canada. [Hua, Lanqi; Marincheva, Gergana; Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Hua, Lanqi; Marincheva, Gergana; Picard, Michael H.] Massachusetts Gen Hosp, Dept Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Hua, Lanqi; Marincheva, Gergana; Picard, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. RP Picard, MH (reprint author), Cardiac Ultrasound Lab, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA. EM mhpicard@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 14 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-2822 EI 1540-8175 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD MAR PY 2015 VL 32 IS 3 BP 496 EP 507 DI 10.1111/echo.12692 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CC8ZA UT WOS:000350655900014 PM 25059625 ER PT J AU Dwojak, S Emerick, KS AF Dwojak, Sunshine Emerick, Kevin S. TI Sentinel lymph node biopsy for cutaneous head and neck malignancies SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE cutaneous squamous cell carcinoma; head and neck cancer; lymph node metastasis; melanoma; Merkel cell carcinoma; sentinel lymph node biopsy ID MERKEL CELL-CARCINOMA; EARLY-STAGE MELANOMA; AMERICAN JOINT COMMITTEE; CLINICAL-PRACTICE GUIDELINE; THIN MELANOMA; SINGLE-INSTITUTION; MULTICENTER TRIAL; MITOTIC RATE; MULTIDISCIPLINARY MANAGEMENT; PROGNOSTIC VALUE AB Sentinel lymph node biopsy (SLNB) is a procedure that can provide critical information regarding pathologic lymph node status and accurate regional staging. This is very important for developing treatment plans and providing prognostic guidance for cutaneous malignancies. The head and neck (HN) region is unique from other body sites due to its complex lymphatic drainage pathways, multiple lymph node basins, proximity of important cranial nerves and potential for contralateral or bilateral drainage. These unique aspects of the HN previously created some uncertainty about the use of SLNB in the HN. This review will discuss the current reliable status of HN SLNB and provide a guide for its current application in cutaneous malignancy of the HN. C1 [Emerick, Kevin S.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Emerick, KS (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Kevin_Emerick@meei.harvard.edu NR 85 TC 1 Z9 1 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD MAR PY 2015 VL 15 IS 3 BP 305 EP 315 DI 10.1586/14737140.2015.990441 PG 11 WC Oncology SC Oncology GA CC5JN UT WOS:000350395000007 PM 25494555 ER PT J AU Guillemette, S Serra, RW Peng, M Hayes, JA Konstantinopoulos, PA Green, MR Cantor, SB AF Guillemette, Shawna Serra, Ryan W. Peng, Min Hayes, Janelle A. Konstantinopoulos, Panagiotis A. Green, Michael R. Cantor, Sharon B. TI Resistance to therapy in BRCA2 mutant cells due to loss of the nucleosome remodeling factor CHD4 SO GENES & DEVELOPMENT LA English DT Article DE BRCA2; CHD4; DNA repair; hereditary cancer ID DNA-DAMAGE RESPONSE; TRANSLESION SYNTHESIS; MI-2/NURD COMPLEX; HOMOLOGOUS RECOMBINATION; SOMATIC MUTATIONS; OVARIAN-CARCINOMA; CANCER GENOMICS; REPAIR; CHEMORESISTANCE; CHEMOTHERAPY AB Hereditary cancers derive from gene defects that often compromise DNA repair. Thus, BRCA-associated cancers are sensitive to DNA-damaging agents such as cisplatin. The efficacy of cisplatin is limited, however, by the development of resistance. One cisplatin resistance mechanism is restoration of homologous recombination (HR), which can result from BRCA reversion mutations. However, in BRCA2 mutant cancers, cisplatin resistance can occur independently of restored BR by a mechanism that remains unknown. Here we performed a genome-wide shRNA screen and found that loss of the nucleosome remodeling factor CHD4 confers cisplatin resistance. Restoration of cisplatin resistance is independent of HR but correlates with restored cell cycle progression, reduced chromosomal aberrations, and enhanced DNA damage tolerance. Suggesting clinical relevance, cisplatin-resistant clones lacking genetic reversion of BRCA2 show de novo loss of CHD4 expression in vitro. Moreover, BRCA2 mutant ovarian cancers with reduced CHD4 expression significantly correlate with shorter progression-free survival and shorter overall survival. Collectively, our findings indicate that CHD4 modulates therapeutic response in BRCA2 mutant cancer cells. C1 [Guillemette, Shawna; Serra, Ryan W.; Peng, Min; Hayes, Janelle A.; Green, Michael R.; Cantor, Sharon B.] Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, UMASS Mem Canc Ctr,Womens Canc Program, Worcester, MA 01605 USA. [Green, Michael R.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA. [Konstantinopoulos, Panagiotis A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Cantor, SB (reprint author), Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, UMASS Mem Canc Ctr,Womens Canc Program, Worcester, MA 01605 USA. EM sharon.cantor@umassmed.edu FU Department of Defense [W81XWH-10-1-0585]; National Institutes of Health [RO1 11150917] FX We thank T. Taniguchi, E. Swisher, and S. Elledge for comments on the manuscript; A. Virbasius for help with lentiviral preparation; and the J. Mao, T. Fazzio, S. Elledge, and S. Ganesan laboratories for sharing reagents. The GFP-HA-CHD4 constructs were generous gifts from S. Jackson, and the HA-BRCA2 construct was a generous gift from R. Scully. We thank A. Venkatesh, B. Morehouse, and S. Nayak for technical assistance. This work was supported by the Department of Defense (W81XWH-10-1-0585 to P.A.K.) and the National Institutes of Health (RO1 11150917 to S.B.C.) as well as charitable contributions from the Lipp Family Foundation and Mr. and Mrs. Edward T. Vitone, Jr. M.R.G. is an investigator of the Howard Hughes Medical Institute. NR 30 TC 12 Z9 12 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 2015 VL 29 IS 5 BP 489 EP 494 DI 10.1101/gad.256214.114 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA CD6HV UT WOS:000351191100003 PM 25737278 ER PT J AU Murn, J Zarnack, K Yang, YJ Durak, O Murphy, EA Cheloufi, S Gonzalez, DM Teplova, M Curk, T Zuber, J Patel, DJ Ule, J Luscombe, NM Tsai, LH Walsh, CA Shi, Y AF Murn, Jernej Zarnack, Kathi Yang, Yawei J. Durak, Omer Murphy, Elisabeth A. Cheloufi, Sihem Gonzalez, Dilenny M. Teplova, Marianna Curk, Tomaz Zuber, Johannes Patel, Dinshaw J. Ule, Jernej Luscombe, Nicholas M. Tsai, Li-Huei Walsh, Christopher A. Shi, Yang TI Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt SO GENES & DEVELOPMENT LA English DT Article DE RNA-binding proteins; cell morphology; gene expression program; neurons; translation; Unkempt ID DENDRITIC SPINE MORPHOGENESIS; HELPER T-CELLS; MESSENGER-RNA; NUCLEOTIDE-RESOLUTION; MUSCLEBLIND PROTEINS; TRANSLATION; GENOME; ACTIVATION; SYNAPSE; MOTIFS AB Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mouse embryos disrupts the shape of migrating neurons, while ectopic expression confers neuronal-like morphology to cells of different nonneuronal lineages. We found that Unkempt is a sequence-specific RNA-binding protein and identified its precise binding sites within coding regions of mRNAs linked to protein metabolism and trafficking. RNA binding is required for Unkempt-induced remodeling of cellular shape and is directly coupled to a reduced production of the encoded proteins. These findings link post-transcriptional regulation of gene expression with cellular shape and have general implications for the development and disease of multicellular organisms. C1 [Murn, Jernej; Shi, Yang] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Murn, Jernej; Shi, Yang] Boston Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. [Zarnack, Kathi; Luscombe, Nicholas M.] European Bioinformat Inst, EMBL, Cambridge CB10 1SD, England. [Zarnack, Kathi] Goethe Univ Frankfurt, Buchmann Inst Mol Life Sci, D-60438 Frankfurt, Germany. [Yang, Yawei J.; Murphy, Elisabeth A.; Gonzalez, Dilenny M.; Walsh, Christopher A.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA. [Yang, Yawei J.; Murphy, Elisabeth A.; Gonzalez, Dilenny M.; Walsh, Christopher A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Yang, Yawei J.; Murphy, Elisabeth A.; Gonzalez, Dilenny M.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Yang, Yawei J.; Murphy, Elisabeth A.; Gonzalez, Dilenny M.; Luscombe, Nicholas M.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Yang, Yawei J.; Murphy, Elisabeth A.; Gonzalez, Dilenny M.; Walsh, Christopher A.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA. [Yang, Yawei J.; Murphy, Elisabeth A.; Gonzalez, Dilenny M.; Walsh, Christopher A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Durak, Omer; Tsai, Li-Huei] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Durak, Omer; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Cheloufi, Sihem] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Cheloufi, Sihem] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Teplova, Marianna; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA. [Curk, Tomaz] Univ Ljubljana, Fac Comp & Informat Sci, Ljubljana 1000, Slovenia. [Zuber, Johannes] Vienna Bioctr, Res Inst Mol Pathol, A-1030 Vienna, Austria. [Ule, Jernej] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Luscombe, Nicholas M.] UCL, Dept Genet Environm & Evolut, UCL Genet Inst, London WC1E 6BT, England. [Luscombe, Nicholas M.] Canc Res UK London Res Inst, London WC2A 3LY, England. [Luscombe, Nicholas M.] Technol Grad Univ, Okinawa Inst Sci, Okinawa 9040495, Japan. RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM murn.jemej@gmail.com; yang_shi@hms.harvard.edu RI Ule, Jernej/C-6315-2013 OI Ule, Jernej/0000-0002-2452-4277 FU Nancy Lurie Marks Post-doctoral Fellowship; EMBL Interdisciplinary Postdocs (EIPOD) fellowship; Stuart H.Q. and Victoria Quan Fellowship; National Institute of General Medical Sciences [T32GM007753]; National Institute of Neurological Disorders and Stroke [R01 NS032457, R01 NS35129]; Manton Center for Orphan Disease Research; National Institutes of Health [GM058012, CA118487, MH096066] FX We thank Yoichiro Sugimoto, Andrea D'Ambrogio, Tom Chittenden, and Angeles Fernandez-Gonzales for advice and assistance with the experiments; Timothy Mitchison, Julian Konig, Linda Van Aelst, Marc Kirschner, Nicholas Ingolia, David Pellman, David van Vactor, John Flanagan, and members of the Shi laboratory for discussion and comments on the manuscript; Crt Gorup for his work on the iCount pipeline; and Francois Guillemot for the pCAGGS-IRES-RFP vector. This study was supported by the Nancy Lurie Marks Post-doctoral Fellowship (J.M.), an EMBL Interdisciplinary Postdocs (EIPOD) fellowship (K.Z.), Stuart H.Q. and Victoria Quan Fellowship (Y.J.Y.), National Institute of General Medical Sciences grant T32GM007753 (Y.J.Y.), National Institute of Neurological Disorders and Stroke grants R01 NS032457 and R01 NS35129 (C.A.W.), the Manton Center for Orphan Disease Research (C.A.W.), and National Institutes of Health grants GM058012, CA118487, and MH096066 (Y.S.). C.A.W. is an Investigator of the Howard Hughes Medical Institute. Y.S. is an American Cancer Society Research Professor. Y.S. is also a co-founder of Constellation Pharmaceuticals, Inc., and a member of its scientific advisory board. NR 49 TC 4 Z9 6 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 2015 VL 29 IS 5 BP 501 EP 512 DI 10.1101/gad.258483.115 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA CD6HV UT WOS:000351191100005 PM 25737280 ER PT J AU Jakobiec, FA Rashid, A Yoon, M AF Jakobiec, Frederick A. Rashid, Alia Yoon, Michael TI Massive and diffuse elastosis of the temporal artery SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Letter ID GIANT-CELL ARTERITIS; PINGUECULA; SCLEROSIS; SKIN C1 [Jakobiec, Frederick A.; Rashid, Alia] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Yoon, Michael] Massachusetts Eye & Ear Infirm, Oculoplast Serv, 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 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0721-832X EI 1435-702X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD MAR PY 2015 VL 253 IS 3 BP 493 EP 495 DI 10.1007/s00417-014-2833-x PG 3 WC Ophthalmology SC Ophthalmology GA CC6WR UT WOS:000350510200021 PM 25341957 ER PT J AU Rakvongthai, Y Worstell, W El Fakhri, G Bian, JG Lorsakul, A Ouyang, JS AF Rakvongthai, Yothin Worstell, William El Fakhri, Georges Bian, Junguo Lorsakul, Auranuch Ouyang, Jinsong TI Spectral CT Using Multiple Balanced K-Edge Filters SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE K-edge filters; rainbow-CT; ross spectrometer; spectral CT; transmission matrix ID ENERGY COMPUTED-TOMOGRAPHY; ATOMIC NUMBERS; X-RAYS; OPTIMIZATION; DETECTORS; SCANNER AB Our goal is to validate a spectral computed tomography (CT) system design that uses a conventional X-ray source with multiple balanced K-edge filters. By performing a simultaneously synthetic reconstruction in multiple energy bins, we obtained a good agreement between measurements and model expectations for a reasonably complex phantom. We performed simulation and data acquisition on a phantom containing multiple rods of different materials using a NeuroLogica CT scanner. Five balanced K-edge filters including Molybdenum, Cerium, Dysprosium, Erbium, and Tungsten were used separately proximal to the X-ray tube. For each sinogram bin, measured filtered vector can be defined as a product of a transmission matrix, which is determined by the filters and is independent of the imaging object, and energy-binned intensity vector. The energy-binned sinograms were then obtained by inverting the transmission matrix followed by a multiplication of the filter measurement vector. For each energy bin defined by two consecutive K-edges, a synthesized energy-binned attenuation image was obtained using filtered back-projection reconstruction. The reconstructed attenuation coefficients for each rod obtained from the experiment was in good agreement with the corresponding simulated results. Furthermore, the reconstructed attenuation coefficients for a given energy bin, agreed with National Institute of Standards and Technology reference values when beam hardening within the energy bin is small. The proposed cost-effective system design using multiple balanced K-edge filters can be used to perform spectral CT imaging at clinically relevant flux rates using conventional detectors and integrating electronics. C1 [Rakvongthai, Yothin; El Fakhri, Georges; Bian, Junguo; Lorsakul, Auranuch; Ouyang, Jinsong] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Rakvongthai, Yothin; El Fakhri, Georges; Bian, Junguo; Ouyang, Jinsong] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Worstell, William] PhotoDiagnost Syst Inc, Boxboro, MA 01719 USA. [Lorsakul, Auranuch] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. RP Ouyang, JS (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. EM ouyang.jinsong@mgh.harvard.edu FU National Institutes of Health (NIH) [R43-EB017591, T32-EB013180] FX This work was supported by the National Institutes of Health (NIH) under Grant R43-EB017591 and Grant T32-EB013180. Y. Rakvongthai and W. Worstell are co-first authors. Asterisk indicates corresponding author. NR 25 TC 3 Z9 4 U1 0 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAR PY 2015 VL 34 IS 3 BP 740 EP 747 DI 10.1109/TMI.2014.2358561 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA CD1YN UT WOS:000350870700006 PM 25252276 ER PT J AU Kim, K Ye, JC Worstell, W Ouyang, JS Rakvongthai, Y El Fakhri, G Li, QZ AF Kim, Kyungsang Ye, Jong Chul Worstell, William Ouyang, Jinsong Rakvongthai, Yothin El Fakhri, Georges Li, Quanzheng TI Sparse-View Spectral CT Reconstruction Using Spectral Patch-Based Low-Rank Penalty SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Concave-convex procedure; difference of convex functions algorithm; low-rank; patch; separable quadratic surrogate; spectral computed tomography (CT) ID PRINCIPAL COMPONENT ANALYSIS; PET IMAGE-RECONSTRUCTION; DUAL-ENERGY CT; COMPUTED-TOMOGRAPHY; BREAST CT; MULTIMATERIAL DECOMPOSITION; MICRO-CT; SYSTEM; REGULARIZATION; OPTIMIZATION AB Spectral computed tomography (CT) is a promising technique with the potential for improving lesion detection, tissue characterization, and material decomposition. In this paper, we are interested in kVp switching-based spectral CT that alternates distinct kVp X-ray transmissions during gantry rotation. This system can acquire multiple X-ray energy transmissions without additional radiation dose. However, only sparse views are generated for each spectral measurement; and the spectra themselves are limited in number. To address these limitations, we propose a penalized maximum likelihood method using spectral patch-based low-rank penalty, which exploits the self-similarity of patches that are collected at the same position in spectral images. The main advantage is that the relatively small number of materials within each patch allows us to employ the low-rank penalty that is less sensitive to intensity changes while preserving edge directions. In our optimization formulation, the cost function consists of the Poisson log-likelihood for X-ray transmission and the nonconvex patch-based low-rank penalty. Since the original cost function is difficult to minimize directly, we propose an optimization method using separable quadratic surrogate and concave convex procedure algorithms for the log-likelihood and penalty terms, which results in an alternating minimization that provides a computational advantage because each subproblem can be solved independently. We performed computer simulations and a real experiment using a kVp switching-based spectral CT with sparse-view measurements, and compared the proposed method with conventional algorithms. We confirmed that the proposed method improves spectral images both qualitatively and quantitatively. Furthermore, our GPU implementation significantly reduces the computational cost. C1 [Kim, Kyungsang; Ouyang, Jinsong; Rakvongthai, Yothin; El Fakhri, Georges; Li, Quanzheng] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Kim, Kyungsang; Ouyang, Jinsong; Rakvongthai, Yothin; El Fakhri, Georges; Li, Quanzheng] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ye, Jong Chul] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Bio Imaging Signal Proc Lab, Taejon 305701, South Korea. [Worstell, William] Photo Diagnost Syst, Boxboro, MA 01719 USA. RP Li, QZ (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. EM li.quanzheng@mgh.harvard.edu RI Ye, Jong Chul/C-1623-2011 FU Korea Science and Engineering Foundation (KOSEF) - Korean government (MEST) [NRF-2009-0081089]; NIH [R01EB013293] FX K. Kim and J. C. Ye are supported by a grant from the Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (MEST) (NRF-2009-0081089). Q. Li is supported by NIH R01EB013293. Asterisk indicates corresponding author. NR 51 TC 9 Z9 9 U1 2 U2 14 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAR PY 2015 VL 34 IS 3 BP 748 EP 760 DI 10.1109/TMI.2014.2380993 PG 13 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA CD1YN UT WOS:000350870700007 PM 25532170 ER PT J AU Lamb, P Sahani, DV Fuentes-Orrego, JM Patino, M Ghosh, A Mendonca, PRS AF Lamb, Peter Sahani, Dushyant V. Fuentes-Orrego, Jorge M. Patino, Manuel Ghosh, Asish Mendonca, Paulo R. S. TI Stratification of Patients With Liver Fibrosis Using Dual-Energy CT SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Computed tomography (CT); dual-energy CT; liver fibrosis; material decomposition; medical imaging ID MAGNETIC-RESONANCE ELASTOGRAPHY; CHRONIC HEPATITIS-C; MR ELASTOGRAPHY; HEPATOCELLULAR-CARCINOMA; COMPUTED-TOMOGRAPHY; NONINVASIVE ASSESSMENT; INITIAL-EXPERIENCE; MULTIDETECTOR CT; UNITED-STATES; FATTY LIVER AB Assessing the severity of liver fibrosis has direct clinical implications for patient diagnosis and treatment. Liver biopsy, typically considered the gold standard, has limited clinical utility due to its invasiveness. Therefore, several imaging-based techniques for staging liver fibrosis have emerged, such as magnetic resonance elastography (MRE) and ultrasound elastography (USE), but they face challenges that include limited availability, high cost, poor patient compliance, low repeatability, and inaccuracy. Computed tomography (CT) can address many of these limitations, but is still hampered by inaccuracy in the presence of confounding factors, such as liver fat. Dual-energy CT (DECT), with its ability to discriminate between different tissue types, may offer a viable alternative to these methods. By combining the "multi-material decomposition" (MMD) algorithm with a biologically driven hypothesis we developed a method for assessing liver fibrosis from DECT images. On a twelve-patient cohort the method produced quantitative maps showing the spatial distribution of liver fibrosis, as well as a fibrosis score for each patient with statistically significant correlation with the severity of fibrosis across a wide range of disease severities. A preliminary comparison of the proposed algorithm against MRE showed good agreement between the two methods. Finally, the application of the algorithm to longitudinal DECT scans of the cohort produced highly repeatable results. We conclude that our algorithm can successfully stratify patients with liver fibrosis and can serve to supplement and augment current clinical practice and the role of DECT imaging in staging liver fibrosis. C1 [Lamb, Peter; Mendonca, Paulo R. S.] GE Global Res, Niskayuna, NY 12309 USA. [Sahani, Dushyant V.; Fuentes-Orrego, Jorge M.; Patino, Manuel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ghosh, Asish] GE Healthcare, Slingerlands, NY 12159 USA. RP Mendonca, PRS (reprint author), Qualcomm Res, San Diego, CA 92121 USA. EM peter.lamb@ge.com; dsahani@partners.org; jmfuentes@partners.org; mpatino@partners.org; aghosh@nycap.rr.com; paulom@qti.qualcomm.com OI Fuentes-Orrego, Jorge/0000-0002-9254-0746 NR 65 TC 9 Z9 9 U1 1 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAR PY 2015 VL 34 IS 3 BP 807 EP 815 DI 10.1109/TMI.2014.2353044 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA CD1YN UT WOS:000350870700013 PM 25181365 ER PT J AU Guo, WJ Qi, H Deng, CY Zhou, HX Deng, SP Li, FR AF Guo, Wei-Jian Qi, Hui Deng, Chun-Yan Zhou, Han-Xin Deng, Shao-Ping Li, Fu-Rong TI The roles of IL-2 and IL-10 enhance anti-CD45RBmAb immune inhibition in allograft skin SO IMMUNOLOGIC RESEARCH LA English DT Article DE Anti-CD45RB monoclonal antibodies; Immune tolerance; Skin allograft; IL-2; IL-10 ID REGULATORY T-CELLS; TRANSPLANTATION TOLERANCE; CUTTING EDGE; TGF-BETA; ANTIBODY; SURVIVAL; CD45RB; DIFFERENTIATION; INTERLEUKIN-2; INFLAMMATION AB As a new type of immune tolerance inducer, anti-CD45RB monoclonal antibodies (anti-CD45RBmAb) can prolong the graft survival time of animal organs or cell transplantation as well as induce stable immune tolerance. Both interleukin (IL)-2 and IL-10 have important roles in the induction and maintenance of immunological tolerance. However, whether these cytokines combined with anti-CD45RBmAb can promote immune tolerance is poorly understood. Therefore, we investigated the effect of IL-2 and IL-10 in vitro and in vivo on the tolerance induction by anti-CD45RBmAb. The changes of Treg and Th17 cells and Th1/Th2 cytokines in anti-CD45RBmAb induced prolongation of skin allograft survival in mice. The finding of a role for IL-2 is novel, of interest, IL-2 promoted anti-CD45RBmAb-induced CD4(+) T cell differentiation into Treg and Th2 cells and suppressed Th17 and Th1 cells. IL-2 enhanced the induction of immune tolerance by anti-CD45RBmAb and significantly prolonged skin graft survival time in vivo. In contrast, this effect should be demonstrated experimentally by neutralizing IL-2 and inhibition of the effect of anti-CD45RBmAb, and neutralizing IL-10 showed no effect for anti-CD45RBmAb-induced tolerance. These data reveal that IL-2 significantly enhances anti-CD45RBmAb-induced immune tolerance via up-regulated T regulatory (Treg) cells and the balance of Th1/Th2 shifts. Conversely, IL-10 showed no effect on anti-CD45RBmAb-induced tolerance. C1 [Guo, Wei-Jian; Qi, Hui; Deng, Chun-Yan; Li, Fu-Rong] Jinan Univ, Shenzhen Peoples Hosp, Key Lab Stem Cell & Cellular Therapy, Clin Med Coll 2, Shenzhen 518020, Peoples R China. [Zhou, Han-Xin; Li, Fu-Rong] Shenzhen Inst Gerontol, Shenzhen 518020, Peoples R China. [Deng, Shao-Ping] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Deng, SP (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM sdeng10@yahoo.com; frli62@yahoo.com FU national 973 special plan of China [2007CB516811]; National Natural Science Foundation of China [30772042]; Natural Science Foundation of Guangdong [6027540]; Science and Technology Project of Shenzhen [201001005] FX This work was supported by the national 973 special plan of China (No. 2007CB516811), the National Natural Science Foundation of China (No. 30772042), The Natural Science Foundation of Guangdong (No. 6027540) and The Science and Technology Project of Shenzhen (No. 201001005). NR 28 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X EI 1559-0755 J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2015 VL 61 IS 3 BP 250 EP 259 DI 10.1007/s12026-014-8618-9 PG 10 WC Immunology SC Immunology GA CC4BO UT WOS:000350295900008 PM 25550088 ER PT J AU Mehta, S Jeffrey, KL AF Mehta, Stuti Jeffrey, Kate L. TI Beyond receptors and signaling: epigenetic factors in the regulation of innate immunity SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Review ID NF-KAPPA-B; HISTONE DEACETYLASE INHIBITOR; TUBERCULOSIS 19-KDA LIPOPROTEIN; SYSTEMIC-LUPUS-ERYTHEMATOSUS; LONG NONCODING RNA; GENE-EXPRESSION; INTERFERON RESPONSE; P-TEFB; ANAPLASMA-PHAGOCYTOPHILUM; TRANSCRIPTION ELONGATION AB The interaction of innate immune cells with pathogens leads to changes in gene expression that elicit our body's first line of defense against infection. Although signaling pathways and transcription factors have a central role, it is becoming increasingly clear that epigenetic factors, in the form of DNA or histone modifications, as well as noncoding RNAs, are critical for generating the necessary cell lineage as well as context-specific gene expression in diverse innate immune cell types. Much of the epigenetic landscape is set during cellular differentiation; however, pathogens and other environmental triggers also induce changes in histone modifications that can either promote tolerance or 'train' innate immune cells for a more robust antigen-independent secondary response. Here we review the important contribution of epigenetic factors to the initiation, maintenance and training of innate immune responses. In addition, we explore how pathogens have hijacked these mechanisms for their benefit and the potential of small molecules targeting chromatin machinery as a way to boost or subdue the innate immune response in disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Jeffrey, KL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 60 Blossom St,Thier340, Boston, MA 02114 USA. EM KJeffrey@mgh.harvard.edu RI Mehta, Stuti/E-9477-2017 OI Mehta, Stuti/0000-0002-6810-6771 FU NIAID NIH HHS [R01 AI107087] NR 109 TC 8 Z9 8 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 EI 1440-1711 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD MAR PY 2015 VL 93 IS 3 BP 233 EP 244 DI 10.1038/icb.2014.101 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CD6OM UT WOS:000351208600005 PM 25559622 ER PT J AU Sansoni, ER Sautter, NB Mace, JC Smith, TL Yawn, JR Lawrence, LA Schlosser, RJ Soler, ZM Mulligan, JK AF Sansoni, E. Ritter Sautter, Nathan B. Mace, Jess C. Smith, Timothy L. Yawn, James R. Lawrence, Lauren A. Schlosser, Rodney J. Soler, Zachary M. Mulligan, Jennifer K. TI Vitamin D-3 as a novel regulator of basic fibroblast growth factor in chronic rhinosinusitis with nasal polyposis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE sinusitis; vitamin D; 25-dihydroxyvitamin D3; fibroblast growth factor-2; polyps ID ALLERGIC FUNGAL RHINOSINUSITIS; SINUS MUCOSA; DENDRITIC CELLS; MURINE MODEL; IN-VITRO; EXPRESSION; ANALOGS; RANTES; INFLAMMATION; DEFICIENCY AB BackgroundThe immunopathogenesis of chronic rhinosinusitis (CRS) is largely unknown, but it is thought that different inflammatory profiles are responsible for the different CRS subtypes. 25-Hydroxyvitamin-D (25-VD3) has been shown to alter inflammatory mediators in other disease processes and 25-VD3 deficiency is associated with CRS with nasal polyps (CRSwNP), but it is unknown if 25-VD3 levels impact local inflammation in CRS. This study investigated the correlation between plasma 25-VD3 and sinonasal mucus monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and basic fibroblast growth factor (bFGF) levels in patients with CRS. MethodsStudy subjects undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2012 to August 2014. Control subjects included patients undergoing ESS for noninflammatory pathology. Blood and sinonasal mucus were collected at the time of ESS. Plasma 25-VD3 was measured by enzyme-linked immunosorbent assay (ELISA) and mucus levels of MCP-1, RANTES, and bFGF by cytometric bead array (CBA). ResultsA total of 57 patients were enrolled and categorized as CRS without nasal polyps (CRSsNP) (n = 31), CRSwNP (n = 14), and controls (n = 12). No significant correlation was found between MCP-1 and 25-VD3. There was a significant negative correlation between 25-VD3 and RANTES (r = -0.612; p = 0.026) and bFGF (r = -0.578; p = 0.039) in CRSwNP patients; however, there was no significant correlation in CRSsNP patients. ConclusionThis data suggests that 25-VD3 may play a role in regulation of RANTES and bFGF expression in CRSwNP. This may occur through regulation of NP fibroblasts or other immune cells. Further investigation is warranted to better elucidate the role of RANTES, bFGF, and 25-VD3 in CRSwNP. C1 [Sansoni, E. Ritter; Sautter, Nathan B.; Mace, Jess C.; Smith, Timothy L.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Yawn, James R.] Med Univ S Carolina, Sch Med, Charleston, SC 29425 USA. [Lawrence, Lauren A.; Schlosser, Rodney J.; Soler, Zachary M.; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Schlosser, Rodney J.; Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Mulligan, JK (reprint author), 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM konopa@musc.edu FU NIH, National Institute on Deafness and Other Communication Disorders (NIDCD) [R01 DC005805]; American Academy of Otolaryngology-Head and Neck Surgery Foundation/American Rhinologic Society (AAO-HNSF/ARS) Centralized Otolaryngology Research Efforts (CORE) [313516] FX Funding sources for the study: NIH, National Institute on Deafness and Other Communication Disorders (NIDCD) (R01 DC005805 to T.L.S.); American Academy of Otolaryngology-Head and Neck Surgery Foundation/American Rhinologic Society (AAO-HNSF/ARS) Centralized Otolaryngology Research Efforts (CORE, #313516). NR 28 TC 4 Z9 4 U1 1 U2 5 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 MAR PY 2015 VL 5 IS 3 BP 191 EP 196 DI 10.1002/alr.21474 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA CD0NG UT WOS:000350770400003 PM 25561293 ER PT J AU Zhang, Z Adappa, ND Lautenbach, E Chiu, AG Doghramji, LJ Cohen, NA Palmer, JN AF Zhang, Zi Adappa, Nithin D. Lautenbach, Ebbing Chiu, Alexander G. Doghramji, Laurel J. Cohen, Noam A. Palmer, James N. TI Coagulase-negative Staphylococcus culture in chronic rhinosinusitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE chronic rhinosinusitis; infection; coagulase-negative Staphylococcus; endoscopic sinus surgery; culture ID CHRONIC SINUSITIS; BACTERIOLOGY; SURGERY; STRAINS AB BackgroundCoagulase-negative Staphylococcus (CoNS) is commonly isolated from patients with chronic rhinosinusitis (CRS). However, the role of CoNS in CRS remains controversial. We aimed to determine the association between positive CoNS culture at functional endoscopic sinus surgery (FESS) and CRS severity. MethodsAdult CRS patients who underwent FESS between October 1, 2007 to December 31, 2011 were recruited. Patient demographics, disease characteristics, medication use, Lund-Mackay computed tomography (CT) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were collected at baseline before FESS. Intraoperative cultures were obtained in a standard manner. Patients were placed into 2 groups based on culture findings: patients with CoNS as the sole positive culture result and patients with all other positive culture results, including CoNS, as part of a polymicrobial culture. ResultsA total of 376 CRS patients met the criteria; 106 patients (28%) had CoNS as their only isolate, 260 (69%) had other positive cultures, and 10 (3%) had no bacterial growth. Compared to patients with other positive cultures, patients with the sole result of CoNS were significantly less likely to have a history of FESS (52% vs 65%, p = 0.019), nasal polyps (50% vs 65%, p = 0.006), and had a better Lund-Mackay CT score (11.95 vs 14.18, p = 0.020). After adjusting for all factors in the multiple logistic regression model, CoNS as the sole positive culture result was independently associated with having no history of FESS (odds ratio [OR] = 0.45; 95% confidence interval [CI], 0.22 to 0.94; p = 0.034). ConclusionPositive intraoperative CoNS cultures alone do not result in increased CRS disease burden by objective or subjective measures as compared to patients with other bacterial or polymicrobial culture isolates. C1 [Zhang, Zi; Lautenbach, Ebbing] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Adappa, Nithin D.; Doghramji, Laurel J.; Cohen, Noam A.; Palmer, James N.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lautenbach, Ebbing] Univ Penn, Dept Med, Perelman Sch Med, Div Infect Dis, 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 FU National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health [K24 AI080942] FX Funding source for the study: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (K24 AI080942 to E.L.). NR 19 TC 2 Z9 2 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 MAR PY 2015 VL 5 IS 3 BP 204 EP 213 DI 10.1002/alr.21439 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA CD0NG UT WOS:000350770400005 PM 25367456 ER PT J AU Sedaghat, AR Kieff, DA Bergmark, RW Cunnane, ME Busaba, NY AF Sedaghat, Ahmad R. Kieff, David A. Bergmark, Regan W. Cunnane, Mary E. Busaba, Nicolas Y. TI Radiographic evaluation of nasal septal deviation from computed tomography correlates poorly with physical exam findings SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE deviated nasal septum; septoplasty; computed tomography; delivery of healthcare; insurance; health; nasal surgical procedures; health policy; practice guidelines ID CHRONIC RHINOSINUSITIS; ALLERGIC RHINITIS; RISK-FACTORS; OBSTRUCTION; SEPTOPLASTY; SINUS; NOSE; OUTCOMES AB BackgroundPerformance of septoplasty is dependent on objective evidence of nasal septal deviation. Although physical examination including anterior rhinoscopy and endoscopic examination is the gold standard for evaluation of septal deviation, third-party payors' reviews of septoplasty claims are often made on computed tomography (CT) findings. However, the correlation between radiographic evaluation of septal deviation with physical examination findings is unknown. MethodsRetrospective, blinded, independent evaluation of septal deviation in 39 consecutive patients from physical examination, including anterior rhinoscopy and endoscopic examination, by an otolaryngologist and radiographic evaluation of sinus CT scan by a neuroradiologist. Four distinct septal locations (nasal valve, cartilaginous, inferior/maxillary crest and osseous septum) were evaluated on a 4-point scale representing (1) 0% to 25%, (2) >25% to 50%, (3) >50% to 75%, and (4) >75% obstruction. Correlation between physical examination and radiographic evaluations was made by Pearson's correlation and quantitative agreement assessed by Krippendorf's alpha. ResultsStatistically significant correlation was detected between physical examination including nasal endoscopy and radiographic assessment of septal deviation only at the osseous septum (p = 0.007, r = 0.425) with low quantitative agreement ( = 0.290). No significant correlation was detected at the cartilaginous septum (p = 0.286, r = 0.175), inferior septum (p = 0.117, r = 0.255), or nasal valve (p = 0.174, r = 0.222). Quantitative agreement at the nasal valve suggested a bias in CT to underestimate physical exam findings ( = -0.490). ConclusionCT is a poor substitute for physical examination, the gold standard, in assessment of septal deviation. Clinical decisions about pursuit of septoplasty or third-party payors' decisions to approve septoplasty should not be made on radiographic evidence. C1 [Sedaghat, Ahmad R.; Kieff, David A.; Bergmark, Regan W.; Busaba, Nicolas Y.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Sedaghat, Ahmad R.; Kieff, David A.; Bergmark, Regan W.; Busaba, Nicolas Y.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Cunnane, Mary E.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu NR 14 TC 3 Z9 3 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 MAR PY 2015 VL 5 IS 3 BP 258 EP 262 DI 10.1002/alr.21445 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA CD0NG UT WOS:000350770400012 PM 25412986 ER PT J AU Kuter, DJ Macahilig, C Grotzinger, KM Poston, SA Wang, PF Dawson, KL Ward, M AF Kuter, David J. Macahilig, Cynthia Grotzinger, Kelly M. Poston, Sara A. Wang, Peter Feng Dawson, Katie L. Ward, Melea TI Treatment patterns and clinical outcomes in patients with chronic immune thrombocytopenia (ITP) switched to eltrombopag or romiplostim SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Clinical outcomes; Eltrombopag; Immune thrombocytopenia; Romiplostim; Treatment switching ID THROMBOPOIETIN RECEPTOR AGONISTS; QUALITY-OF-LIFE; PURPURA; EFFICACY AB This observational study aimed to assess real-world treatment patterns and clinical outcomes for patients with chronic immune thrombocytopenia (ITP) currently being treated with eltrombopag or romiplostim after switching from corticosteroids, rituximab, or the alternate thrombopoietin receptor agonist (TPO-RA). The study examined the rationale for switching to TPO-RA therapy using aided responses. Dosing patterns were also analyzed before and after switching. Treatment outcomes were assessed through platelet counts at multiple time points including treatment initiation and after switching at the last office visit. A total of 280 patients were enrolled whose active therapy for ITP was replaced with either eltrombopag (n = 130) or romiplostim (n = 150). Efficacy-related issues (desired platelet count not achieved and/or lack of response to prior therapy) were the main drivers for therapy switching among all patients (54 % for eltrombopag vs. 57 % for romiplostim). Platelet counts at the last office visit showed improvement compared with counts at the initiation of either eltrombopag or romiplostim treatment. No significant differences were noted when comparing clinical outcomes between the eltrombopag and romiplostim treatment cohorts. Our results suggest that switching to the other TPO-RA may be beneficial if there is inadequate response to treatment with the initial TPO-RA. C1 [Kuter, David J.] Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. [Macahilig, Cynthia] Med Data Analyt, Res Operat, Parsippany, NJ USA. [Grotzinger, Kelly M.] GlaxoSmithKline, Value Evidence & Outcomes, Collegeville, PA USA. [Poston, Sara A.] GlaxoSmithKline, US Hlth Outcomes, Philadelphia, PA USA. [Wang, Peter Feng] Bristol Myers Squibb Co, Hlth Econ & Outcomes Res, Princeton, NJ USA. [Dawson, Katie L.] Katie Louise Dawson LLC, Clin Dev, New Hope, PA USA. [Ward, Melea] GlaxoSmithKline, US Hlth Outcomes, Res Triangle Pk, NC USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Div Hematol, 55 Fruit St, Boston, MA 02114 USA. EM kuter.david@mgh.harvard.edu FU GlaxoSmithKline FX This study was conducted in partnership with Medical Data Analytics, which received funding from GlaxoSmithKline for data collection, analysis, and interpretation of results. We would like to acknowledge the following individuals: Robert Simons, PhD, President, Global Health Economics and Outcomes Research (GHEOR) for analytical support; Lavanya Sudharshan, MS, Lead Analyst, Pharmerit International, for medical writing support. All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors (ICMJE). D.K., P.F.W., and K.G. contributed to study design and reviewed data. C.M. contributed to data collection. K.G. and S.P. contributed to data analyses. C.M., K.G., S.P., K.G., M.W., P.F.W., and D.K. contributed to interpretation of results. S.P., D.K., K.D., and M.W. helped with writing of the manuscript. All authors revised the manuscript and approved its final contents. NR 21 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0925-5710 EI 1865-3774 J9 INT J HEMATOL JI Int. J. Hematol. PD MAR PY 2015 VL 101 IS 3 BP 255 EP 263 DI 10.1007/s12185-014-1731-7 PG 9 WC Hematology SC Hematology GA CD2IH UT WOS:000350899600007 PM 25586660 ER PT J AU Farhat, MR Mitnick, CD Franke, MF Kaur, D Sloutsky, A Murray, M Jacobson, KR AF Farhat, M. R. Mitnick, C. D. Franke, M. F. Kaur, D. Sloutsky, A. Murray, M. Jacobson, K. R. TI Concordance of Mycobacterium tuberculosis fluoroquinolone resistance testing: implications for treatment SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE drug susceptibility testing; multidrug-resistant tuberculosis; critical concentration ID MOXIFLOXACIN; GATIFLOXACIN AB Fluoroquinolone (FQ) drug susceptibility testing (DST) is an important step in the design of effective treatment regimens for multidrug-resistant tuberculosis. Here we compare ciprofloxacin, ofloxacin and moxifloxacin (MFX) resistance results from 226 multidrug-resistant samples. The low level of concordance observed suggests that DST should be performed for the specific FQ planned for clinical use. The results also support the new World Health Organization recommendation for testing MFX at a critical concentration of 2.0 mu g/ml. C1 [Farhat, M. R.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Farhat, M. R.; Mitnick, C. D.; Franke, M. F.; Murray, M.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Mitnick, C. D.] Brigham & Womens Hosp, Dept Global Hlth Equ, Boston, MA 02115 USA. [Kaur, D.; Sloutsky, A.] Univ Massachusetts, Sch Med, Massachusetts Supranatl TB Reference Lab, Boston, MA 02125 USA. [Murray, M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Jacobson, K. R.] Boston Univ, Sch Med, Infect Dis Sect, Boston, MA 02118 USA. [Jacobson, K. R.] Univ Stellenbosch, Dept Sci & Technol, Natl Res Fdn,Ctr Excellence Biomed TB Res, MRC,Fac Med & Hlth Sci,Ctr Mol & Cellular Biol,Di, ZA-7505 Tygerberg, South Africa. RP Farhat, MR (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, 641 Huntington Ave,Suite 4A, Boston, MA 02115 USA. EM mrfarhat@partners.org OI Farhat, Maha/0000-0002-3871-5760; Jacobson, Karen/0000-0003-4239-3685 FU Harvard Center for AIDS Research (CFAR), a National Institutes of Health (NIH) [P30 AI060354]; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Institute of Child Health and Human Development; National Institute on Drug Abuse, National Institute of Mental Health; National Institute on Aging; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences; Fogarty International Center (FIC); Office of AIDS Research (Bethesda, MD, USA); American Lung Association (Washington DC, USA) Biomedical Research Grant [RG-270912-N]; Parker B. Francis Fellowship; NIH/FIC [K01 TW009213]; NIH NIAID [U19-AI109755] FX This work was supported by the Harvard Center for AIDS Research (CFAR), a National Institutes of Health (NIH) funded program (P30 AI060354), which is supported by the following NIH Co-Funding and Participating Institutes and Centers: National Institute of Allergy and Infectious Diseases (NIAID), National Cancer Institute, National Institute of Child Health and Human Development, National Institute on Drug Abuse, National Institute of Mental Health, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of General Medical Sciences, Fogarty International Center (FIC), and Office of AIDS Research (Bethesda, MD, USA). This work was also supported by the American Lung Association (Washington DC, USA) Biomedical Research Grant (RG-270912-N) and the Parker B. Francis Fellowship (MRF), the NIH/FIC (K01 TW009213 KRJ) and NIH NIAID (U19-AI109755, MM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 11 TC 6 Z9 6 U1 2 U2 4 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 EI 1815-7920 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD MAR PY 2015 VL 19 IS 3 BP 339 EP 341 DI 10.5588/ijtld.14.0814 PG 3 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA CC9SO UT WOS:000350711700019 PM 25686144 ER PT J AU Lipska, KJ Ross, JS Miao, YH Shah, ND Lee, SJ Steinman, MA AF Lipska, Kasia J. Ross, Joseph S. Miao, Yinghui Shah, Nilay D. Lee, Sei J. Steinman, Michael A. TI Potential Overtreatment of Diabetes Mellitus in Older Adults With Tight Glycemic Control SO JAMA INTERNAL MEDICINE LA English DT Article ID SEVERE HYPOGLYCEMIA; EPIDEMIOLOGIC ANALYSIS; CLINICAL COMPLEXITY; GLUCOSE CONTROL; RISK; MORTALITY; ASSOCIATION; DEMENTIA; COMPLICATIONS; PREVALENCE AB IMPORTANCE In older adults with multiple serious comorbidities and functional limitations, the harms of intensive glycemic control likely exceed the benefits. OBJECTIVES To examine glycemic control levels among older adults with diabetes mellitus by health status and to estimate the prevalence of potential overtreatment of diabetes. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of the data on 1288 older adults (>= 65 years) with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 2001 through 2010 who had a hemoglobin A(1c) (HbA(1c)) measurement. All analyses incorporated complex survey design to produce nationally representative estimates. EXPOSURES Health status categories: very complex/poor, based on difficulty with 2 or more activities of daily living or dialysis dependence; complex/intermediate, based on difficulty with 2 or more instrumental activities of daily living or presence of 3 or more chronic conditions; and relatively healthy if none of these were present. MAIN OUTCOMES AND MEASURES Tight glycemic control (HbA(1c) level, <7%) and use of diabetes medications likely to result in hypoglycemia (insulin or sulfonylureas). RESULTS Of 1288 older adults with diabetes, 50.7%(95% CI, 46.6%-54.8%), representing 3.1 million (95% CI, 2.7-3.5), were relatively healthy, 28.1%(95% CI, 24.8%-31.5%), representing 1.7 million (95% CI, 1.4-2.0), had complex/intermediate health, and 21.2%(95% CI, 18.3%-24.4%), representing 1.3 million (95% CI, 1.1-1.5), had very complex/poor health. Overall, 61.5%(95% CI, 57.5%-65.3%), representing 3.8 million (95% CI, 3.4-4.2), had an HbA1c level of less than 7%; this proportion did not differ across health status categories (62.8%[95% CI, 56.9%-68.3%]) were relatively healthy, 63.0%(95% CI, 57.0%-68.6%) had complex/intermediate health, and 56.4%(95% CI, 49.7%-62.9%) had very complex/poor health (P = .26). Of the older adults with an HbA(1c) level of less than 7%, 54.9% (95% CI, 50.4%-59.3%) were treated with either insulin or sulfonylureas; this proportion was similar across health status categories (50.8%[95% CI, 45.1%-56.5%] were relatively healthy, 58.7% [95% CI, 49.4%-67.5%] had complex/intermediate health, and 60.0%[95% CI, 51.4%-68.1%] had very complex/poor health; P = .14). During the 10 study years, there were no significant changes in the proportion of older adults with an HbA(1c) level of less than 7% (P = .34), the proportion with an HbA(1c) level of less than 7% who had complex/intermediate or very complex/poor health (P = .27), or the proportion with an HbA(1c) level of less than 7% who were treated with insulin or sulfonylureas despite having complex/intermediate or very complex/poor health (P = .65). CONCLUSIONS AND RELEVANCE Although the harms of intensive treatment likely exceed the benefits for older patients with complex/intermediate or very complex/poor health status, most of these adults reached tight glycemic targets between 2001 and 2010. Most of them were treated with insulin or sulfonylureas, which may lead to severe hypoglycemia. Our findings suggest that a substantial proportion of older adults with diabetes were potentially overtreated. C1 Yale Univ, Sch Med, Dept Internal Med, Endocrinol Sect, New Haven, CT 06510 USA. [Lipska, Kasia J.; Ross, Joseph S.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Ross, Joseph S.] Yale Univ, Sch Med, Dept Internal Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Ross, Joseph S.] Yale Univ, Sch Med, Dept Internal Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. [Ross, Joseph S.] Yale Univ, Dept Hlth Policy & Management, Sch Publ Hlth, New Haven, CT 06520 USA. [Miao, Yinghui; Lee, Sei J.; Steinman, Michael A.] San Francisco VA Med Ctr, Div Geriatr, Dept Med, San Francisco, CA USA. [Shah, Nilay D.] Mayo Clin, Knowledge & Evaluat Res Unit, Dept Hlth Sci Res, Rochester, MN USA. [Shah, Nilay D.] Mayo Clin, Div Hlth Care Policy & Res, Dept Hlth Sci Res, Rochester, MN USA. [Lee, Sei J.; Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. RP Lipska, KJ (reprint author), Yale Univ, Endocrinol Sect, Dept Internal Med, Sch Med, POB 208020, New Haven, CT 06520 USA. EM kasia.lipska@yale.edu FU Pepper Center Career Development Award [P30 AG21342]; National Institute on Aging [R03 AG045086, K23-AG048359, K08 AG032886]; Yale Center for Investigation Scholar Award Clinical and Translational Science Award [UL1 TR000142]; American Federation for Aging Research through the Paul B. Beeson Career Development Program (Drs Lipska and Ross); National Institutes of Health and the American Federation for Aging Research [1K23-AG030999, P30-AG044281] FX This study was supported by grant P30 AG21342 from the Pepper Center Career Development Award, Grants for Early Medical/Surgical Specialists' Transition to Aging Research No. R03 AG045086 from the National Institute on Aging, Yale Center for Investigation Scholar Award Clinical and Translational Science Award number UL1 TR000142, and National Institute on Aging grant K23-AG048359 (Dr Lipska); the American Federation for Aging Research through the Paul B. Beeson Career Development Program (Drs Lipska and Ross); National Institute on Aging grant K08 AG032886 (Dr Ross); and National Institutes of Health and the American Federation for Aging Research grants 1K23-AG030999 and P30-AG044281 (Dr Steinman). NR 33 TC 56 Z9 56 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2015 VL 175 IS 3 BP 356 EP 362 DI 10.1001/jamainternmed.2014.7345 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CD0YF UT WOS:000350799600011 PM 25581565 ER PT J AU Yeh, RW Mauri, L Wolf, RE Romm, IK Lovett, A Shahian, D Normand, SL AF Yeh, Robert W. Mauri, Laura Wolf, Robert E. Romm, Iyah K. Lovett, Ann Shahian, David Normand, Sharon-Lise TI Population Trends in Rates of Coronary Revascularization SO JAMA INTERNAL MEDICINE LA English DT Letter ID HOSPITALIZED MYOCARDIAL-INFARCTION; OUTCOMES C1 [Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Mauri, Laura] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Wolf, Robert E.; Lovett, Ann; Normand, Sharon-Lise] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Romm, Iyah K.] Hlth Policy Commiss, Commonwealth Massachusetts, Boston, MA USA. [Shahian, David] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Shahian, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Qual & Safety, Boston, MA USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 8-843, Boston, MA 02114 USA. EM ryeh@partners.org FU NHLBI NIH HHS [1K23HL118138, K23 HL118138] NR 6 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2015 VL 175 IS 3 BP 454 EP 456 DI 10.1001/jamainternmed.2014.7129 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CD0YF UT WOS:000350799600033 PM 25559059 ER PT J AU Schmajuk, G Bozic, KJ Yazdany, J AF Schmajuk, Gabriela Bozic, Kevin J. Yazdany, Jinoos TI Using Medicare Data to Understand Health Care Value: Measures of Incremental Cost and Effectiveness are Both Needed to Estimate Value Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Schmajuk, Gabriela; Yazdany, Jinoos] Univ Calif San Francisco, Dept Med Rheumatol, San Francisco, CA 94143 USA. [Schmajuk, Gabriela] San Francisco Vet Affairs VA Med Ctr, San Francisco, CA USA. [Bozic, Kevin J.] Univ Calif San Francisco, Dept Orthoped Surg, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Schmajuk, G (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Mailstop 111R, San Francisco, CA 94121 USA. EM gabriela.schmajuk@ucsf.edu FU NIAMS NIH HHS [K23 AR060259, K23 AR063770] NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2015 VL 175 IS 3 BP 462 EP 463 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CD0YF UT WOS:000350799600041 PM 25730567 ER PT J AU Grady, D Redberg, RF AF Grady, Deborah Redberg, Rita F. TI Advancing Medical Professionalism and the Choosing Wisely Campaign Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Grady, Deborah; Redberg, Rita F.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Dept Med, 550 16th St, San Francisco, CA 94158 USA. EM Deborah.Grady@ucsf.edu NR 1 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 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2015 VL 175 IS 3 BP 465 EP 465 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CD0YF UT WOS:000350799600045 PM 25730572 ER PT J AU Butala, NM Johnson, BK Horwitz, LI AF Butala, Neel M. Johnson, Benjamin K. Horwitz, Leora I. TI Mortality Trends in Diabetes Mellitus Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID DEATH CERTIFICATE COMPLETION; ACCURACY C1 [Butala, Neel M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Johnson, Benjamin K.] Yale Univ, Sch Med, Yale Ctr Analyt Sci, New Haven, CT USA. [Horwitz, Leora I.] NYU, Sch Med, Dept Populat Hlth, Div Healthcare Delivery Sci, New York, NY USA. [Horwitz, Leora I.] NYU, Sch Med, Dept Med, Div Gen Internal Med & Clin Innovat, New York, NY USA. RP Horwitz, LI (reprint author), NYU Sch Med, Dept Populat Hlth, 550 First Ave,TRB Room 607, New York, NY 10016 USA. EM Leora.horwitz@nyumc.org OI Horwitz, Leora/0000-0003-1800-6040 NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2015 VL 175 IS 3 BP 470 EP 470 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CD0YF UT WOS:000350799600054 PM 25730582 ER PT J AU Howard, RG Samuels, J Gyftopoulos, S Krasnokutsky, S Leung, J Swearingen, CJ Pillinger, MH AF Howard, Rennie G. Samuels, Jonathan Gyftopoulos, Soterios Krasnokutsky, Svetlana Leung, Joseph Swearingen, Christopher J. Pillinger, Michael H. TI Presence of Gout Is Associated With Increased Prevalence and Severity of Knee Osteoarthritis Among Older Men Results of a Pilot Study SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE gout; hyperuricemia; knee osteoarthritis; biomarker; musculoskeletal ultrasound ID RANDOMIZED CONTROLLED-TRIAL; URIC-ACID; ASYMPTOMATIC HYPERURICEMIA; OCCUPATIONAL ACTIVITY; MONOSODIUM URATE; DANGER SIGNAL; RISK-FACTORS; ARTHRITIS; POPULATION; ULTRASOUND AB Background: Gout and osteoarthritis (OA) are the most prevalent arthritides, but their relationship is neither well established nor well understood. Objectives: We assessed whether a diagnosis of gout or asymptomatic hyperuricemia(AH) is associated with increased prevalence/severity of knee OA. Methods: One hundred nineteen male patients aged 55 to 85 years were sequentially enrolled from the primary care clinics of an urban Veterans Affairs hospital, assessed and categorized into 3 groups: gout (American College of Rheumatology Classification Criteria), AH (serum urate >= 6.8 mg/dL, no gout), and control (serum urate <6.8 mg/dL, no gout). Twenty-five patients from each group subsequently underwent formal assessment of knee OA presence and severity (American College of Rheumatology Clinical/Radiographic Criteria, Kellgren-Lawrence grade). Musculoskeletal ultrasound was used to detect monosodium urate deposition at the knees and first metatarsophalangeal joints. Results: The study showed 68.0% of gout, 52.0% of AH, and 28.0% of age-matched control subjects had knee OA (gout vs control, P = 0.017). Odds ratio for knee OA in gout versus control subjects was 5.46 prior to and 3.80 after adjusting for body mass index. Gout subjects also had higher Kellgren-Lawrence grades than did the control subjects (P = 0.001). Subjects with sonographically detected monosodium urate crystal deposition on cartilage were more likely to have OA than those without (60.0 vs 27.5%, P = 0.037), with crystal deposition at the first metatarsophalangeal joints correlating most closely with OA knee involvement. Conclusions: Knee OA was more prevalent in gout patients versus control subjects and intermediate in AH. Knee OA was more severe in gout patients versus control subjects. C1 [Howard, Rennie G.; Samuels, Jonathan; Krasnokutsky, Svetlana; Pillinger, Michael H.] NYU, NYU Langone Med Ctr, Sch Med, Div Rheumatol, New York, NY USA. [Howard, Rennie G.; Samuels, Jonathan; Krasnokutsky, Svetlana; Leung, Joseph; Pillinger, Michael H.] US Dept Vet Affairs, Dept Med, New York Harbor Hlth Care Syst, New York, NY USA. [Gyftopoulos, Soterios] NYU, Dept Radiol, Sch Med, NYU Langone Med Ctr, New York, NY 10016 USA. [Leung, Joseph] NYU, Div Gen Internal Med, Sch Med, NYU Langone Med Ctr, New York, NY 10016 USA. [Swearingen, Christopher J.] Univ Arkansas Med Sci, Dept Pediat, Biostat Sect, Little Rock, AR 72205 USA. RP Pillinger, MH (reprint author), NYU Hosp Joint Dis, 301 E 17th St,Room 1410, New York, NY 10003 USA. EM michael.pillinger@nyumc.org OI samuels, jonathan/0000-0002-1513-770X; Pillinger, Michael/0000-0003-3168-1542 FU National Institutes of Health T32 Training Grant [5T32AR007176]; Arthritis Foundation New York Chapter; Clinical and Translational Science Institute of NYU School of Medicine; CTSA from the National Center for the Advancement of Translational Science, National Institutes of Health [UL1TR000038] FX This work was supported by a National Institutes of Health T32 Training Grant 5T32AR007176 (R.G.H.; principal investigator Steven B. Abramson, MD), a Fellowship Award in Osteoarthritis from the Arthritis Foundation New York Chapter (R.G.H.) and Pilot Award from the Clinical and Translational Science Institute of NYU School of Medicine (R.G.H.). M.H.P. is supported in part by CTSA grant UL1TR000038 from the National Center for the Advancement of Translational Science, National Institutes of Health. NR 49 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD MAR PY 2015 VL 21 IS 2 BP 63 EP 71 DI 10.1097/RHU.0000000000000217 PG 9 WC Rheumatology SC Rheumatology GA CD0KX UT WOS:000350762600003 PM 25710856 ER PT J AU Neumeyer, AM O'Rourke, JA Massa, A Lee, H Lawson, EA McDougle, CJ Misra, M AF Neumeyer, Ann M. O'Rourke, Julia A. Massa, Alexandra Lee, Hang Lawson, Elizabeth A. McDougle, Christopher J. Misra, Madhusmita TI Brief Report: Bone Fractures in Children and Adults with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Autism; Fractures; Low bone density; Osteoporosis ID OSTEOPOROTIC FRACTURES; MINERAL CONTENT; ADOLESCENTS; EPIDEMIOLOGY; DENSITY; DISABILITIES; CHILDHOOD; BURDEN; SWEDEN; RISK AB Peripubertal boys with autism spectrum disorder (ASD) have lower bone mineral density (BMD) than typically developing controls. However, it is not clear whether lower BMD in ASD results in an increased fracture rate. This study examined the rate of fractures in children and adults with and without ASD using a national database of emergency room visits (Nationwide Emergency Department Sample). A higher odds ratio for hip fractures in children and young adults (3-22 years) as well as older adults (23-50 years) with ASD than those without ASD, and a higher odds ratio for forearm and spine fractures in women ages 23-50 with ASD were found. Further studies are necessary to better understand the decreased bone density in ASD and its implications for fracture development. C1 [Neumeyer, Ann M.; O'Rourke, Julia A.; Massa, Alexandra; McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Lexington, MA 02114 USA. [Neumeyer, Ann M.; O'Rourke, Julia A.; Massa, Alexandra; McDougle, Christopher J.] Harvard Univ, Sch Med, Lexington, MA USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Lawson, Elizabeth A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Lawson, Elizabeth A.; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. [Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. RP Neumeyer, AM (reprint author), Massachusetts Gen Hosp, Lurie Ctr Autism, One Maguire Rd, Lexington, MA 02114 USA. EM aneumeyer@mgh.harvard.edu FU NIH [K24HD071843, 1 UL1 RR025758-01]; Nancy Lurie Marks Family Foundation FX This research was supported in part by NIH grants K24HD071843 and 1 UL1 RR025758-01. The authors also thank the Nancy Lurie Marks Family Foundation for their support and partnership. NR 34 TC 5 Z9 5 U1 1 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAR PY 2015 VL 45 IS 3 BP 881 EP 887 DI 10.1007/s10803-014-2228-1 PG 7 WC Psychology, Developmental SC Psychology GA CC4FK UT WOS:000350306600023 PM 25193141 ER PT J AU Jones, D Zhao, FM Brell, J Lewis, MA Loprinzi, CL Weiss, M Fisch, MJ AF Jones, Desiree Zhao, Fengmin Brell, Joanna Lewis, Mark A. Loprinzi, Charles L. Weiss, Matthias Fisch, Michael J. TI Neuropathic symptoms, quality of life, and clinician perception of patient care in medical oncology outpatients with colorectal, breast, lung, and prostate cancer SO JOURNAL OF CANCER SURVIVORSHIP LA English DT Article DE Colorectal cancer; Neuropathy; Neuropathic pain; Numbness/tingling; Quality of life ID INDUCED PERIPHERAL NEUROPATHY; ACUTE PAIN SYNDROME; COLON-CANCER; INDUCED NEUROTOXICITY; ADJUVANT TREATMENT; CHEMOTHERAPY; OXALIPLATIN; TRIAL; FLUOROURACIL; LEUCOVORIN AB We investigated how treatment-induced neuropathic symptoms are associated with patients' quality of life (QOL) and clinician-reported difficulty in caring for patients. Data were obtained from 3,106 outpatients with colorectal, breast, lung, or prostate cancer on numbness/tingling (N/T), neuropathic pain, and QOL. Clinicians reported the degree of difficulty in caring for patients' physical and psychological symptoms. For all patients, moderate to severe N/T was associated with poor QOL (OR = 1.82, 95 % CI = 1.47-2.26, P < 0.001) but neuropathic pain was not (OR = 1.31, 95 % CI = 0.94-1.83, P = 0.114). Moderate to severe N/T and neuropathic pain were associated with increased care difficulty (OR = 1.49, 95 % CI = 1.27-1.74, P < 0.001 for N/T, and OR = 1.46, 95 % CI = 1.15-1.84, P = 0.002 for neuropathic pain). The association of neuropathic pain with care difficulty was most significant in patients with colorectal cancer (CRC) (OR = 2.32, 95 % CI = 1.41-3.83, P = 0.001). Baseline neuropathic pain was associated with declining QOL in CRC patients (OR = 2.08, 95 % CI = 1.21-3.58, P = 0.008). Clinicians may experience increased care difficulty for patients of all cancer types with moderate to severe N/T or neuropathic pain; care difficulty due to neuropathic pain may be higher for CRC patients. Nearly half the patients of all cancer types with moderate to severe N/T may expect poor short-term QOL; CRC-but not other-patients with baseline neuropathic pain are likely to experience declining QOL. About half of patients with moderate to severe N/T (any cancer type) may expect poor QOL in the short term; CRC patients with baseline neuropathic pain in particular may experience declining QOL. C1 [Jones, Desiree; Lewis, Mark A.; Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA. [Zhao, Fengmin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Brell, Joanna] Metrohlth Med Ctr, Cleveland, OH USA. [Loprinzi, Charles L.] Mayo Clin, Breast Dept, Rochester, MN USA. [Loprinzi, Charles L.] Mayo Clin, Dept Oncol, Rochester, MN USA. [Weiss, Matthias] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. RP Jones, D (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, 1515 Holcombe Blvd,Unit 410, Houston, TX 77030 USA. EM djones1@mdanderson.org FU Public Health Service Grants [CA37604, CA17145]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was supported in part by Public Health Service Grants CA37604, CA17145, and grants from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Drs. Fisch and Zhao had full access to the data. NR 30 TC 1 Z9 1 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 EI 1932-2267 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD MAR PY 2015 VL 9 IS 1 BP 1 EP 10 DI 10.1007/s11764-014-0379-x PG 10 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA CC4ZB UT WOS:000350364400001 PM 25023039 ER PT J AU Zhou, ES Hu, JC Kantoff, PW Recklitis, CJ AF Zhou, Eric S. Hu, Jim C. Kantoff, Philip W. Recklitis, Christopher J. TI Identifying suicidal symptoms in prostate cancer survivors using brief self-report SO JOURNAL OF CANCER SURVIVORSHIP LA English DT Article DE Suicide ideation; Prostate cancer; Cancer survivorship ID REPLICATION NCS-R; ADULT SURVIVORS; CHILDHOOD-CANCER; GENERAL-POPULATION; IDEATION; RISK; DEPRESSION; DEATH; THOUGHTS; REGISTER AB Prostate cancer (PC) survivors are at elevated risk for completed suicide even many years post-treatment. Despite this risk, practical and efficient methods for assessing these symptoms have not been established. We sought to determine if suicidal symptoms could be effectively and efficiently identified in a cohort of PC survivors, and whether these men were receptive to emotional health interventions. Six hundred fifty-six PC survivors, an average of 5 years post-diagnosis, completed eight self-report items about suicidal symptoms and behavior in the past 7 days, and 12 months, as well as medical utilization and interest in emotional health support. Between 3.6 and 17.9 % of PC survivors endorsed a single suicidal ideation item, and denied all other ideation. All survivors who endorsed serious suicidal ideation/behavior also endorsed either passive or active ideation. 58.3 % of survivors denied any suicidal symptoms within the past week, but endorsed it within the past year. Most survivors had medical provider contact within the past year and were open to receiving information about emotional health interventions. Suicidal ideation in PC survivors cannot be accurately evaluated using only a one-item screen, or by inquiring within a single time frame. In both research and clinical settings, the evaluation for suicidal ideation in PC survivors should utilize multiple questions, across several time periods. It is possible to skip queries about serious ideation/behavior if passive or active ideation is denied. Once identified, medical providers should refer these men to psychosocial providers who can offer emotional support. C1 [Zhou, Eric S.; Kantoff, Philip W.; Recklitis, Christopher J.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Zhou, Eric S.; Kantoff, Philip W.; Recklitis, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. [Hu, Jim C.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Christopher_Recklitis@dfci.harvard.edu NR 45 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 EI 1932-2267 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD MAR PY 2015 VL 9 IS 1 BP 59 EP 67 DI 10.1007/s11764-014-0385-z PG 9 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA CC4ZB UT WOS:000350364400007 PM 25135206 ER PT J AU Blackmon, JE Liptak, C Recklitis, CJ AF Blackmon, Jaime E. Liptak, Cori Recklitis, Christopher J. TI Development and preliminary validation of a short form of the Beck Depression Inventory for Youth (BDI-Y) in a sample of adolescent cancer survivors SO JOURNAL OF CANCER SURVIVORSHIP LA English DT Article DE Beck Depression Inventory for Youth; Cancer; Survivorship; Adolescents; Depression ID CHILDHOOD-CANCER; ADULT SURVIVORS; PROJECT REACH; OUTCOMES; CHILDREN; ILLNESS AB The aim of this study was to analyze adolescent cancer survivors' responses to the Beck Depression Inventory for Youth (BDI-Y) to determine if a short form of the measure could be developed that would accurately identify survivors with clinically significant levels of depressive symptoms. Two hundred two adolescent survivors (mean age = 15.39 years, SD = 1.93) completed the BDI-Y at a single time point and were divided into two groups: a derivation sample (n = 105) and a replication sample (n = 97). Based on correlations with the total BDI-Y score in the derivation sample, items were selected for inclusion in three potential short forms, with 6, 8, and 11 items, respectively. These short forms were then evaluated against the full BDI-Y scale first in the derivation sample and subsequently in the replication sample (n = 97). Each of the three short forms had high correlations with the total BDI-Y scale (r > 0.95), good internal consistency (alpha > 0.80), and good overall discrimination compared to a standard BDI-Y cutoff score (AUC > 0.90). The eight-item short form demonstrated notable consistency across the derivation and replication samples, with high sensitivity and specificity using a cutoff score of a parts per thousand yen5, making it a promising tool for clinical screening. Abbreviated versions of the BDI-Y can accurately detect depression in adolescent cancer survivors. An eight-item short form demonstrates strong psychometric properties and potential for use as a screening measure in this population, while the 6- and 11-item short forms may be suited to other applications. C1 [Blackmon, Jaime E.; Recklitis, Christopher J.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02215 USA. [Liptak, Cori; Recklitis, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Liptak, Cori] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, Perini Family Survivors Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM Christopher_Recklitis@dfci.harvard.edu NR 50 TC 3 Z9 3 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 EI 1932-2267 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD MAR PY 2015 VL 9 IS 1 BP 107 EP 114 DI 10.1007/s11764-014-0394-y PG 8 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA CC4ZB UT WOS:000350364400010 PM 25164512 ER PT J AU Metra, M Cotter, G El-Khorazaty, J Davison, BA Milo, O Carubelli, V Bourge, RC Cleland, JG Jondeau, G Krum, H O'Connor, CM Parker, JD Torre-Amione, G van Veldhuisen, DJ Rainisio, M Kobrin, I Mcmurray, JJ Teerlink, JR AF Metra, Marco Cotter, Gad El-Khorazaty, Jill Davison, Beth A. Milo, Olga Carubelli, Valentina Bourge, Robert C. Cleland, John G. Jondeau, Guillaume Krum, Henry O'Connor, Christopher M. Parker, John D. Torre-Amione, Guillermo van Veldhuisen, Dirk J. Rainisio, Maurizio Kobrin, Isaac Mcmurray, John J. Teerlink, John R. TI Acute Heart Failure in the Elderly: Differences in Clinical Characteristics, Outcomes, and Prognostic Factors in the VERITAS Study SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; age; outcomes ID ACUTE MYOCARDIAL-INFARCTION; NATRIURETIC-PEPTIDE; RELAX-AHF; TROPONIN ELEVATION; RENAL DYSFUNCTION; TASK-FORCE; HIGH-RISK; ASSOCIATION; TRIAL; HOSPITALIZATION AB Background: Acute heart failure (HF) is common in the elderly, but the association of age with clinical outcomes and prognostic factors has not been examined thoroughly. Methods and Results: We analyzed the clinical and laboratory characteristics and the outcomes of 1,347 patients with acute HF enrolled in the VERITAS trial. Subjects were subdivided based on their median age of 72 years. Older patients had a higher prevalence of comorbidities and a higher prevalence of hypertension and atrial fibrillation. During a mean follow-up of 149 +/- 61 days, 432 patients (32.1%) reached the composite end point of death, in-hospital worsening HF, or HF rehospitalization by 30 days, and 135 patients (10.4%) died by 90 days, with a worse outcome in elderly patients in both cases. At multivariable analysis, different variables were related with each of these outcomes in elderly compared with younger patients. Regarding deaths at 90 days, plasma urea nitrogen and hemoglobin levels were predictive only in the younger patients, whereas respiratory rate and albumin levels were associated with mortality only in the older patients. Conclusions: Elderly patients with acute HF have different clinical characteristics and poorer outcomes. Prognostic variables differ in elderly compared with younger patients. C1 [Metra, Marco; Carubelli, Valentina] Univ Brescia, Dept Med & Surg Specialties, Radiol Sci & Publ Hlth, Cardiol, Brescia, Italy. [Cotter, Gad; El-Khorazaty, Jill; Davison, Beth A.; Milo, Olga] Momentum Res Inc, Durham, NC USA. [Bourge, Robert C.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Cleland, John G.] Royal Bronzpton & Harefield Hosp Trust, Natl Heart & Lung Inst, London, England. [Cleland, John G.] Univ Hull, Hull York Med Sch, Kingston Upon Hull, Yorks, England. [Jondeau, Guillaume] Hop Bichat Claude Bernard, Serv Cardiol, F-75877 Paris, France. [Krum, Henry] Monash Univ, Alfred Hosp, Dept Epidemiol & Prevent Med, Monash Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. [O'Connor, Christopher M.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Parker, John D.] Mt Sinai Hosp, Dept Med, Div Cardiol, New York, NY USA. [Parker, John D.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Torre-Amione, Guillermo] Houston Methodist Hosp, Houston, TX USA. [Torre-Amione, Guillermo] Tecnol Monterrey, Monterrey, Mexico. [van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Rainisio, Maurizio] AbaNovus, San Remo, Italy. [Kobrin, Isaac] Actel Pharmaceut, Allschwil, Switzerland. [Mcmurray, John J.] Univ Glasgow, Glasgow, Lanark, Scotland. [Teerlink, John R.] San Francisco VA Med Ctr, Sect Cardiol, San Francisco, CA USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Metra, M (reprint author), Spedali Civil Brescia, Cardiol, Piazza Spedali Civili 1, I-25123 Brescia, Italy. EM metramarco@libero.it OI Cleland, John/0000-0002-1471-7016; Parker, John/0000-0003-1949-2669; Metra, Marco/0000-0001-6691-8568; mcmurray, john/0000-0002-6317-3975 NR 41 TC 8 Z9 8 U1 0 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD MAR PY 2015 VL 21 IS 3 BP 179 EP 188 DI 10.1016/j.cardfail.2014.12.012 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CD1ML UT WOS:000350838900001 PM 25573829 ER PT J AU Maisel, A Xue, Y Greene, SJ Pang, PS Januzzi, JL Pina, IL Defilippi, C Butler, J AF Maisel, Alan Xue, Yang Greene, Stephen J. Pang, Peter S. Januzzi, James L. Pina, Ileana L. Defilippi, Christopher Butler, Javed TI The Potential Role of Natriuretic Peptide-Guided Management for Patients Hospitalized for Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Review DE Heart failure; natriuretic peptides; readmission; hospitalization ID ARTERY CATHETERIZATION EFFECTIVENESS; INITIATE LIFESAVING TREATMENT; PROBNP REDUCTION PERCENTAGE; ACUTE MYOCARDIAL-INFARCTION; SYSTOLIC BLOOD-PRESSURE; NT-PROBNP; EMERGENCY-DEPARTMENT; OPTIMIZE-HF; ORGANIZED PROGRAM; CONTROLLED-TRIAL AB There are >1 million hospitalizations for heart failure (HF) in the United States annually. After discharge, 25% of these patients are rehospitalized within 30 days, and 30% are dead within 1 year. To date, all trials in patients with acute HF (AHF) have failed to improve post-discharge outcomes. There remains a need for an effective objective risk stratification strategy that is capable of reliably identifying patients at heightened risk for readmission and informing discharge decision making. Natriuretic peptide (NP) levels during and after AHF hospitalization can provide valuable information regarding congestion status and chronic remodeling stress. The lack of sensitivity and inter-rater reliability of physical examination, and failure to achieve dry weight in many patients before discharge, renders the use of NP to guide therapy to prevent readmission an attractive option. NP levels can be used across the spectrum of ARP care settings, ranging from the emergency department and inpatient stay to post-discharge follow-up and chronic management. This review summarizes available data and provides an expert opinion on the potential role of NPs to reduce HF readmissions. C1 [Maisel, Alan; Xue, Yang] Univ Calif San Diego, Dept Med, Div Cardiol, San Diego, CA 92103 USA. [Maisel, Alan; Xue, Yang] San Diego Vet Adm Med Ctr, San Diego, CA USA. [Greene, Stephen J.] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Pang, Peter S.] Indiana Univ, Sch Med, Dept Emergency Med, Indianapolis, IN 46204 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Pina, Ileana L.] Albert Einstein Coll Med, Dept Med, Div Cardiol, New York, NY USA. [Defilippi, Christopher] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Butler, Javed] SUNY Stony Brook, Dept Med, Div Cardiol, Stony Brook, NY 11794 USA. RP Butler, J (reprint author), SUNY Stony Brook, Hlth Sci Ctr, Div Cardiol, T-16,Room 080, Stony Brook, NY 11794 USA. EM javed.butler@stonybrookmedicine.edu FU Alere; Abbott; BG Medicine; Brahms; Roche; Critical Diagnostics; Siemens; National Institutes of Health; European Union; Health Resources and Services Administration; Amgen; Gambr; Otsuka; Bio Control FX Alan Maisel, MD, has received research support from Alere, Abbott, BG Medicine, and Brahms; is a consultant to Alere, Critical Diagnostics, Sphingotect, BG Medicine, and EFG Diagnostics; has had speaking engagements for BG Medicine and Alere; and is a cofounder of Cardero Therapeutics and My Life Diagnostics. Yang Xue, MD, has received travel grants from Alere, Brahms, and BG Medicine. Stephen J. Greene, MD, has no potential conflicts. Peter S. Pang, MD, reports consultancies and honoraria from Janssen, Medtronic, Novartis, Otsuka, Trevena, scPharmaceuticals, Cornerstone Therapeutics, and BG Medicine; and has has received research support from Alere. James L. Januzzi, MD, has received research support from Roche, Critical Diagnostics, Siemens; and is a consultant to Amgen, Novartis, Zensun, Critical Diagnostics, and Sphingotec. Ileana L. Pi a, MD, MPH, has no potential conflicts. Christopher DeFilippi, MD, has received research support from Roche and Alere; is a consultant to Roche; and has received an honorarium from Siemens. Javed Butler, MD, MPH, has received research support from the National Institutes of Health, European Union, and Health Resources and Services Administration; has participated in clinical trials supported by Amgen, Gambro, Otsuka, and Bio Control; is a consultant to Amgen, BG Medicine, Celladon, Harvest, Gambro, Ono Pharma, Trevena, Bayer, Medtronic, Stemedica, and GE Healthcare; and has stock options with Stemedica. NR 70 TC 6 Z9 6 U1 0 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD MAR PY 2015 VL 21 IS 3 BP 233 EP 239 DI 10.1016/j.cardfail.2014.11.009 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CD1ML UT WOS:000350838900007 PM 25433362 ER PT J AU Crowley, B Howe, YJ McDougle, CJ AF Crowley, Brittany Howe, Yamini J. McDougle, Christopher J. TI Topiramate for Weight Loss in Two Young Adult Women with Autism Spectrum Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Letter ID PERVASIVE DEVELOPMENTAL DISORDERS; DOUBLE-BLIND; CHILDREN; RISPERIDONE; ADOLESCENTS; GAIN C1 [Crowley, Brittany] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Howe, Yamini J.; McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Lexington, MA 02421 USA. [Howe, Yamini J.; McDougle, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. RP McDougle, CJ (reprint author), Massachusetts Gen Hosp, Lurie Ctr Autism, 1 Maguire Rd, Lexington, MA 02421 USA. EM cmcdougle@partners.org NR 12 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 EI 1557-8992 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD MAR 1 PY 2015 VL 25 IS 2 BP 183 EP 185 DI 10.1089/cap.2014.0140 PG 3 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA CD4MT UT WOS:000351057800015 PM 25746055 ER PT J AU Zhu, XR Messer, JS Wang, YW Lin, FF Cham, CM Chang, J Billiar, TR Lotze, MT Boone, DL Chang, EB AF Zhu, Xiaorong Messer, Jeannette S. Wang, Yunwei Lin, Fanfei Cham, Candace M. Chang, Jonathan Billiar, Timothy R. Lotze, Michael T. Boone, David L. Chang, Eugene B. TI Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROUP BOX-1 PROTEIN; CALPAIN-MEDIATED CLEAVAGE; BOWEL-DISEASE; INTESTINAL INFLAMMATION; IN-VITRO; AUTOPHAGY; APOPTOSIS; MICE; CASPASE; CALPASTATIN AB The intracellular protein HMGB1 is released from cells and acts as a damage-associated molecular pattern molecule during many diseases, including inflammatory bowel disease (IBD); however, the intracellular function of HMGB1 during inflammation is poorly understood. Here, we demonstrated that cytosolic HMGB1 regulates apoptosis by protecting the autophagy proteins beclin 1 and ATG5 from calpain-mediated cleavage during inflammation. Colitis in mice with an intestinal epithelial cell-specific Hmgb1 deletion and patients with IBD were both characterized by increased calpain activation, beclin 1 and ATG5 cleavage, and intestinal epithelial cell (IEC) death compared with controls. In vitro cleavage assays and studies of enteroids verified that HMGB1 protects beclin 1 and ATG5 from calpain-mediated cleavage events that generate proapoptotic protein fragments. Together, our results indicate that HMGB1 is essential for mitigating the extent and severity of inflammation-associated cellular injury by controlling the switch between the proautophagic and proapoptotic functions of beclin 1 and ATG5 during inflammation. Moreover, these studies demonstrate that HMGB1 is pivotal for reducing tissue injury in IBD and other complex inflammatory disorders. C1 [Zhu, Xiaorong; Messer, Jeannette S.; Wang, Yunwei; Lin, Fanfei; Cham, Candace M.; Boone, David L.; Chang, Eugene B.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Chang, Jonathan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Billiar, Timothy R.; Lotze, Michael T.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. RP Chang, EB (reprint author), Univ Chicago, Knapp Ctr Biomed Discovery, 900 E 57th St,9th Floor,Room 9130, Chicago, IL 60637 USA. EM echang@medicine.bsd.uchicago.edu OI Messer, Jeannette/0000-0002-5072-3835 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH through Digestive Disease Research Core Center [DK-42086, DK47722, DK097268, 1F32DK082104, P30 DK42086]; National Institute of Allergy and Infectious Diseases (NIAID) [AI083375]; Gastrointestinal Research Foundation; Crohn's and Colitis Foundation of America; Broad Medical Research Program; Peter and Carol Goldman Family Research Fund; Harry and Leona Helmsley Charitable Trust (SHARE) FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH through Digestive Disease Research Core Center grants DK-42086 (to E.B. Chang), DK47722 (to E.B. Chang), DK097268 (to E.B. Chang), 1F32DK082104 (to J.S. Messer), and P30 DK42086 (to J.S. Messer). Support was also provided by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (AI083375, to D.L. Boone); the Gastrointestinal Research Foundation; the Crohn's and Colitis Foundation of America (to J.S. Messer and Y. Wang); the Broad Medical Research Program (to D.L. Boone); the Peter and Carol Goldman Family Research Fund; and the Harry and Leona Helmsley Charitable Trust (SHARE). NR 64 TC 23 Z9 25 U1 1 U2 22 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2015 VL 125 IS 3 BP 1098 EP 1110 DI 10.1172/JCI76344 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CC8KF UT WOS:000350616500025 PM 25642769 ER PT J AU Mallipattu, SK Horne, SJ D'Agati, V Narla, G Liu, RJ Frohman, MA Dickman, K Chen, EY Ma'ayan, A Bialkowska, AB Ghaleb, AM Nandan, MO Jain, MK Daehn, I Chuang, PY Yang, VW He, JC AF Mallipattu, Sandeep K. Horne, Sylvia J. D'Agati, Vivette Narla, Goutham Liu, Ruijie Frohman, Michael A. Dickman, Kathleen Chen, Edward Y. Ma'ayan, Avi Bialkowska, Agnieszka B. Ghaleb, Amr M. Nandan, Mandayam O. Jain, Mukesh K. Daehn, Ilse Chuang, Peter Y. Yang, Vincent W. He, John C. TI Kruppel-like factor 6 regulates mitochondrial function in the kidney SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; HIV-ASSOCIATED NEPHROPATHY; NEPHROTIC SYNDROME; OXIDATIVE STRESS; GENE-EXPRESSION; RETINOIC ACID; DOXORUBICIN; APOPTOSIS; PODOCYTES; INJURY AB Maintenance of mitochondrial structure and function is critical for preventing podocyte apoptosis and eventual glomerulosclerosis in the kidney; however, the transcription factors that regulate mitochondrial function in podocyte injury remain to be identified. Here, we identified Kruppel-like factor 6 (KLF6), a zinc finger domain transcription factor, as an essential regulator of mitochondrial function in podocyte apoptosis. We observed that podocyte-specific deletion of Klf6 increased the susceptibility of a resistant mouse strain to adriamycin-induced (ADR-induced) focal segmental glomerulosclerosis (FSGS). KLF6 expression was induced early in response to ADR in mice and cultured human podocytes, and prevented mitochondrial dysfunction and activation of intrinsic apoptotic pathways in these podocytes. Promoter analysis and chromatin immunoprecipitation studies revealed that putative KLF6 transcriptional binding sites are present in the promoter of the mitochondrial cytochrome c oxidase assembly gene (SCO2), which is critical for preventing cytochrome c release and activation of the intrinsic apoptotic pathway. Additionally, KLF6 expression was reduced in podocytes from HIV-1 transgenic mice as well as in renal biopsies from patients with HIV-associated nephropathy (HIVAN) and FSGS. Together, these findings indicate that KLF6-dependent regulation of the cytochrome c oxidase assembly gene is critical for maintaining mitochondrial function and preventing podocyte apoptosis. C1 [Mallipattu, Sandeep K.; Horne, Sylvia J.] SUNY Stony Brook, Dept Med, Div Nephrol, Stony Brook, NY 11790 USA. [D'Agati, Vivette] Columbia Univ, Dept Pathol, New York, NY USA. [Narla, Goutham] Case Western Reserve Univ, Inst Transformat Mol Med, Cleveland, OH 44106 USA. [Liu, Ruijie; Daehn, Ilse; Chuang, Peter Y.; He, John C.] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [Frohman, Michael A.; Dickman, Kathleen] SUNY Stony Brook, Dept Pharmacol, Stony Brook, NY 11790 USA. [Chen, Edward Y.; Ma'ayan, Avi; He, John C.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Bialkowska, Agnieszka B.; Ghaleb, Amr M.; Nandan, Mandayam O.; Yang, Vincent W.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11790 USA. [Jain, Mukesh K.] Case Western Reserve Univ, Dept Med, Res Inst, Case Cardiovasc Inst, Cleveland, OH 44106 USA. [He, John C.] James J Peters VA Med Ctr, Renal Sect, New York, NY USA. RP He, JC (reprint author), Mt Sinai Sch Med, Dept Med Nephrol, One Gustave L Levy Pl,Box 1243m, New York, NY 10029 USA. EM sandeep.mallipattu@stonybrookmedicine.edu; cijiang.he@mssm.edu OI daehn, ilse/0000-0001-9915-5376 FU NIH/NIDDK [1 R01 DK078897-01, 1K0801DK102519-01]; Chinese 973 fund [2012CB517601]; Dialysis Clinic Inc. (Paul Teschan Research Grant) FX This work was supported by NIH/NIDDK 1 R01 DK078897-01 and Chinese 973 fund 2012CB517601 to J.C. He; and NIH/NIDDK 1K0801DK102519-01 and Dialysis Clinic Inc. (Paul Teschan Research Grant) to S.K. Mallipattu. We thank Ali Gharavi, Natalia Papeta, and Roel Sterken (Division of Nephrology, Department of Medicine, Columbia University, New York, New York, USA) for their guidance and constructive feedback on the data presented in this article. NR 46 TC 10 Z9 12 U1 3 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2015 VL 125 IS 3 BP 1347 EP 1361 DI 10.1172/JCI77084 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CC8KF UT WOS:000350616500045 PM 25689250 ER PT J AU Nelson, BD Ahn, R Markovchick, V Hines, RA Lauretti, AR Lauretti, JR Dahl-Regis, M Burke, TF AF Nelson, Brett D. Ahn, Roy Markovchick, Vince Hines, Rosemary A. Lauretti, Alexandre R. Lauretti, Julien R. Dahl-Regis, Merceline Burke, Thomas F. TI EMERGENCY CARE AND REFERRAL AMONG ISOLATED ISLAND POPULATIONS IN THE BAHAMAS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency medicine; emergency referral; island populations; isolated populations; Bahamas ID ULTRASOUND AB Background: Isolated island populations face unique health challenges. In the Bahamas, the islands of Mayaguana, Inagua, Crooked Island, Acklins, and Long Cay-referred to as the MICAL Constituency-are among the most isolated. Objectives: Our objective was to better understand regional emergency care needs and capabilities, and determine how emergency care can be optimized among island populations. Methods: During the summer of 2013, the project team conducted semi-structured key-informant interviews and small-group discussions among all health care teams in the MICAL region, as well as a community-based household survey on the island of Mayaguana. The interviews and small-group discussions consisted of open-response questions related to health care services, equipment, supplies, medications, and human resources. The community-based survey examined the prevalence of chronic noncommunicable diseases (CNCDs) and associated risk factors affecting the inhabitants of the region. Results: The average number of annual emergency referrals from each of the MICAL islands was approximately 25-30, and reasons for referrals off-island included chest pain, abdominal pain, trauma, and dysfunctional uterine bleeding. Traditional prehospital care is not established in the MICAL Constituency. Providers reported feelings of isolation from the distant health system in Nassau. Whereas most clinics have a well-stocked pharmacy of oral medications, diagnostic capabilities are limited. The household survey showed a high prevalence of CNCDs and associated risk factors. Conclusion: Ongoing in-service emergency care training among MICAL providers is needed. Additional equipment could significantly improve emergency care capabilities, specifically, equipment to manage chest pain, fractures, and other trauma. Community-based preventive services and education could improve the overall health of the island populations. (C) 2015 Elsevier Inc. C1 [Nelson, Brett D.; Ahn, Roy; Markovchick, Vince; Hines, Rosemary A.; Lauretti, Alexandre R.; Lauretti, Julien R.; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Nelson, Brett D.; Ahn, Roy; Burke, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA. [Markovchick, Vince] Denver Hlth Med Ctr, Dept Emergency Med, Denver, CO USA. [Dahl-Regis, Merceline] Govt Bahamas, Minist Hlth, Nassau, Bahamas. RP Nelson, BD (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Zero Emerson St,Suite 104, Boston, MA 02114 USA. OI Nelson, Brett/0000-0002-5049-1798 FU Mayaguana Development Advisory Board FX The authors would like to thank Tim Haffner, Vincent Vanderpool-Wallace, the Mayaguana Development Advisory Board, and the Ministry of Health of the Bahamas for their critical assistance with this study. We also sincerely thank the many health care providers, administrators, and community members for their selfless time in participating. Funding for this research was provided by the Mayaguana Development Advisory Board. NR 9 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 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD MAR PY 2015 VL 48 IS 3 BP 356 EP 365 DI 10.1016/j.jemermed.2014.09.069 PG 10 WC Emergency Medicine SC Emergency Medicine GA CC7XH UT WOS:000350581300023 PM 25534899 ER PT J AU Kruse, GR Khan, SM Zaslavsky, AM Ayanian, JZ Sequist, TD AF Kruse, Gina R. Khan, Sami M. Zaslavsky, Alan M. Ayanian, John Z. Sequist, Thomas D. TI Overuse of Colonoscopy for Colorectal Cancer Screening and Surveillance SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colorectal cancer screening; colonoscopy; overuse; efficiency ID SOCIETY-TASK-FORCE; PRIMARY-CARE PHYSICIANS; NATIONAL-SURVEY; CLINICAL GUIDELINES; POLYP SURVEILLANCE; CONSENSUS UPDATE; POLYPECTOMY; MEDICARE; RECOMMENDATION; RATIONALE AB Ongoing efforts to increase colorectal cancer (CRC) screening rates have raised concerns that these exams may be overused, thereby subjecting patients to unnecessary risks and wasting healthcare resources. Our aim was to measure overuse of screening and surveillance colonoscopies among average-risk adults, and to identify correlates of overuse. Our approach was a retrospective cohort study using electronic health record data for patients 50-65 years old with no personal history of CRC or colorectal adenomas with an incident CRC screening colonoscopy from 2001 to 2010 within a multispecialty physician group practice. We measured time to next screening or surveillance colonoscopy and predictors of overuse (exam performed more than one year earlier than guideline recommended intervals) of colonoscopies. We identified 1,429 adults who had an incident colonoscopy between 2001 and 2010, and they underwent an additional 871 screening or surveillance colonoscopies during a median follow-up of 6 years. Most follow-up screening colonoscopies (88 %) and many surveillance colonoscopies (49 %) repeated during the study represented overuse. Time to next colonoscopy after incident screening varied by exam findings (no polyp: median 6.9 years, interquartile range [IQR]: 5.1-10.0; hyperplastic polyp: 5.7 years, IQR: 4.9-9.7; low-risk adenoma: 5.1 years, IQR: 3.3-6.3; high-risk adenoma: 2.9 years, IQR: 2.0-3.4, p < 0.001). In logistic regression models of colonoscopy overuse, an endoscopist recommendation for early follow-up was strongly associated with overuse of screening colonoscopy (OR 6.27, 95 % CI: 3.15-12.50) and surveillance colonoscopy (OR 13.47, 95 % CI 6.61-27.46). In a multilevel logistic regression model, variation in the overuse of screening colonoscopy was significantly associated with the endoscopist performing the previous exam. Overuse of screening and surveillance exams are common and should be monitored by healthcare systems. Variations in endoscopist recommendations represent targets for interventions to reduce overuse. C1 [Kruse, Gina R.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Khan, Sami M.; Ayanian, John Z.; Sequist, Thomas D.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Zaslavsky, Alan M.; Ayanian, John Z.; Sequist, Thomas D.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Ayanian, John Z.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Sequist, Thomas D.] Partners Healthcare Syst, Boston, MA USA. RP Kruse, GR (reprint author), 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM gkruse@mgh.harvard.edu FU National Cancer Institute [R01 CA112367, 5R25 CA057711-20]; Health Resources and Services Administration [T32HP12706]; Ryoichi Sasakawa Fellowship Fund FX The study was supported by the National Cancer Institute R01 CA112367. Dr. Kruse was supported by Health Resources and Services Administration training grant T32HP12706, the Ryoichi Sasakawa Fellowship Fund, and the National Cancer Institute 5R25 CA057711-20. NR 40 TC 9 Z9 9 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2015 VL 30 IS 3 BP 277 EP 283 DI 10.1007/s11606-014-3015-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD2EG UT WOS:000350886500006 PM 25266407 ER PT J AU Zuchowski, JL Rose, DE Hamilton, AB Stockdale, SE Meredith, LS Yano, EM Rubenstein, LV Cordasco, KM AF Zuchowski, Jessica L. Rose, Danielle E. Hamilton, Alison B. Stockdale, Susan E. Meredith, Lisa S. Yano, Elizabeth M. Rubenstein, Lisa V. Cordasco, Kristina M. TI Challenges in Referral Communication Between VHA Primary Care and Specialty Care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care; specialty care; communication; electronic health records; veterans ID CENTERED MEDICAL HOME; HEALTH-CARE; DISPERSED COLLABORATION; PHYSICIAN REFERRALS; UNITED-STATES; COORDINATION; SYSTEM; DETERMINANTS; CONSULTATION; NEIGHBOR AB Poor communication between primary care providers (PCPs) and specialists is a significant problem and a detriment to effective care coordination. Inconsistency in the quality of primary-specialty communication persists even in environments with integrated delivery systems and electronic medical records (EMRs), such as the Veterans Health Administration (VHA). The purpose of this study was to measure ease of communication and to characterize communication challenges perceived by PCPs and primary care personnel in the VHA, with a particular focus on challenges associated with referral communication. The study utilized a convergent mixed-methods design: online cross-sectional survey measuring PCP-reported ease of communication with specialists, and semi-structured interviews characterizing primary-specialty communication challenges. 191 VHA PCPs from one regional network were surveyed (54 % response rate), and 41 VHA PCPs and primary care staff were interviewed. PCP-reported ease of communication mean score (survey) and recurring themes in participant descriptions of primary-specialty referral communication (interviews) were analyzed. Among PCPs, ease-of-communication ratings were highest for women's health and mental health (mean score of 2.3 on a scale of 1-3 in both), and lowest for cardiothoracic surgery and neurology (mean scores of 1.3 and 1.6, respectively). Primary care personnel experienced challenges communicating with specialists via the EMR system, including difficulty in communicating special requests for appointments within a certain time frame and frequent rejection of referral requests due to rigid informational requirements. When faced with these challenges, PCPs reported using strategies such as telephone and e-mail contact with specialists with whom they had established relationships, as well as the use of an EMR-based referral innovation called "eConsults" as an alternative to a traditional referral. Primary-specialty communication is a continuing challenge that varies by specialty and may be associated with the likelihood of an established connection already in place between specialty and primary care. Improvement in EMR systems is needed, with more flexibility for the communication of special requests. Building relationships between PCPs and specialists may also facilitate referral communication. C1 [Zuchowski, Jessica L.; Rose, Danielle E.; Hamilton, Alison B.; Stockdale, Susan E.; Meredith, Lisa S.; Yano, Elizabeth M.; Rubenstein, Lisa V.; Cordasco, Kristina M.] VA Greater Angeles Healthcare Syst, Ctr Study Healthcare Innovat, Implementat & Policy, Sepulveda, CA USA. [Hamilton, Alison B.; Stockdale, Susan E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Meredith, Lisa S.; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Yano, Elizabeth M.] UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Rubenstein, Lisa V.; Cordasco, Kristina M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Zuchowski, JL (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Innovat Implementat & Policy, Bldg 25,16111 Plummer St, Sepulveda, CA 91343 USA. EM jessica.zuchowski@va.gov FU VHA Office of Patient Care Services [XVA 65-018]; VA HSRD Service [RCS 05-195] FX Funding for the VAIL-PCC PACT Demonstration Laboratory initiative was provided to Drs. Lisa V. Rubenstein, Elizabeth M. Yano, and Lisa Altman from the VHA Office of Patient Care Services (Project #XVA 65-018). Dr. Yano's time was supported by a Senior Research Career Scientist Award from the VA HSR&D Service (Project #RCS 05-195). The views expressed within are solely those of the authors, and do not necessarily represent the views of the Department of Veterans Affairs or the United States government. NR 32 TC 7 Z9 7 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2015 VL 30 IS 3 BP 305 EP 311 DI 10.1007/s11606-014-3100-x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD2EG UT WOS:000350886500010 PM 25410884 ER PT J AU Parast, L Doyle, B Damberg, CL Shetty, K Ganz, DA Wenger, NS Shekelle, PG AF Parast, Layla Doyle, Brian Damberg, Cheryl L. Shetty, Kanaka Ganz, David A. Wenger, Neil S. Shekelle, Paul G. TI Challenges in Assessing the Process-Outcome Link in Practice SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE quality improvement; program evaluation; medicare; preventive care; randomized trials ID ACUTE MYOCARDIAL-INFARCTION; SENSITIVITY-ANALYSIS; BETA-BLOCKADE; MORTALITY; QUALITY; CARE; CONFOUNDERS; ASSOCIATION; ADHERENCE; TRIALS AB The expanded use of clinical process-of-care measures to assess the quality of health care in the context of public reporting and pay-for-performance applications has led to a desire to demonstrate the value of such efforts in terms of improved patient outcomes. The inability to observe associations between improved delivery of clinical processes and improved clinical outcomes in practice has raised concerns about the value of holding providers accountable for delivery of clinical processes of care. Analyses that attempt to investigate this relationship are fraught with many challenges, including selection of an appropriate outcome, the proximity of the outcome to the receipt of the clinical process, limited power to detect an effect, small expected effect sizes in practice, potential bias due to unmeasured confounding factors, and difficulties due to changes in measure specification over time. To avoid potentially misleading conclusions about an observed or lack of observed association between a clinical process of care and an outcome in the context of observational studies, individuals conducting and interpreting such studies should carefully consider, evaluate, and acknowledge these types of challenges. C1 [Parast, Layla; Damberg, Cheryl L.; Shetty, Kanaka; Ganz, David A.; Wenger, Neil S.; Shekelle, Paul G.] RAND Corp, Santa Monica, CA 90407 USA. [Doyle, Brian; Ganz, David A.; Wenger, Neil S.; Shekelle, Paul G.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ganz, David A.; Shekelle, Paul G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Parast, L (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM parast@rand.org OI Doyle, Brian/0000-0003-2782-2306 FU Centers for Medicare and Medicaid Services [HHSM-500-2011-AZ0S.SIP.02] FX This project was funded by the Centers for Medicare and Medicaid Services under contract number HHSM-500-2011-AZ0S.SIP.02. NR 31 TC 4 Z9 4 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2015 VL 30 IS 3 BP 359 EP 364 DI 10.1007/s11606-014-3150-0 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD2EG UT WOS:000350886500022 PM 25564435 ER PT J AU Kronlage, SC Menendez, ME AF Kronlage, Steven C. Menendez, Mariano E. TI The Benefit of Carpal Tunnel Release in Patients With Electrophysiologically Moderate and Severe Disease SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Carpal tunnel; electrodiagnostic; severe; moderate; release; benefit ID NERVE-CONDUCTION; FOLLOW-UP; SYMPTOMS; SURGERY; OUTCOMES; OLDER; AGE; QUESTIONNAIRE; DECOMPRESSION; TRIAL AB Purpose To compare change in numbness and pain after carpal tunnel release in patients with electrophysiologically moderate and severe disease. Methods We tested the primary null hypothesis that there is no difference in the total Carpal Tunnel Symptoms Scale score 3 months after surgery between patients with moderate and those with severe disease. Ninety-five patients (47 in the moderate cohort, and 48 in the severe cohort) who had miniopen carpal tunnel release between November 2011. and November 2013 were identified from our prospectively collected database. For each patient, the total Carpal Tunnel Symptoms Scale score, as well the numbness and pain subscale scores, at the preoperative and postoperative (2-wk, 1-mo, 2-mo, 3-mo, >= 1-y) visits were documented. The data were analyzed with repeated-measures analysis of variance. Results Three months after surgery, patients with moderate carpal tunnel syndrome (CTS) reported, on average, no symptoms, and patients with severe disease had reduced but unresolved symptoms. Although symptoms diminished in both groups from the preoperative assessment to the 2-week postoperative assessment, patients with severe CTS had comparatively more severe symptoms at all time points with the exception of pain at 2 weeks and 1 year or longer after surgery, at which times there was no significant difference. At 1 year or longer after surgery, 1 (2%) patient with moderate CTS and 9 (19%) patients with severe CTS reported continued symptoms. Preoperative electrodiagnostic severity was the factor most predictive of symptom scores. Conclusions Patients with severe CTS experience considerable reduction in symptoms after surgery but should be informed that recovery, may be more prolonged and, in some cases, incomplete 1 year after carpal tunnel release, particularly with regard to numbness. Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved. C1 [Kronlage, Steven C.] Andrews Inst, Gulf Breeze, FL 32561 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Kronlage, SC (reprint author), Andrews Inst, Suite 205,1040 Gulf Breeze Pkwy, Gulf Breeze, FL 32561 USA. EM skronlage@yahoo.com NR 32 TC 0 Z9 0 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2015 VL 40 IS 3 BP 438 EP 444 DI 10.1016/j.jhsa.2014.12.012 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CD4CH UT WOS:000351029700002 PM 25708432 ER PT J AU Webber, T Patel, SP Pensak, M Fajolu, O Rozental, TD Wolf, JM AF Webber, Tracy Patel, Shaun P. Pensak, Michael Fajolu, Olukemi Rozental, Tamara D. Wolf, Jennifer Moriatis TI Correlation Between Distal Radial Cortical Thickness and Bone Mineral Density SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Distal radius fracture; bone mineral density; osteoporosis; cortical thickness; fragility fracture ID PROXIMAL HUMERUS; OSTEOPOROSIS; FRACTURES; HIP; WOMEN; PREDICTORS; MORBIDITY; MORTALITY AB Purpose To determine interobserver reliability in measuring the cortical thickness of distal radiuses on posteroanterior radiographs obtained at the time of injury and to determine whether there is a correlation between distal radius cortical thickness and hip and lumbar spine scores on dual-energy x-ray absorptiometry (DXA). Methods Four orthopedic surgeons at 2 academic institutions who were blinded to the study protocol reviewed standard posteroanterior wrist radiographs of 80 women over age 50 years with distal radius fractures with DXA data obtained within the past 2 years. Radial bicortical widths were measured at 50 and 70 mm proximal to the distal ulnar articular surface, and mean bicortical thickness was calculated from radiographs of the injured wrist. Average bicortical width was compared with each patient's femoral and lumbar spine bone density measures. Data were analyzed using Pearson correlation coefficients and simple linear regression. Inter-rater reliability was evaluated using intra-class correlation coefficients. Results The inter-rater reliability for average bicortical thickness had a high intra-class correlation coefficient value of 0.91. Average bicortical thickness showed a statistically significant positive relationship with femoral bone density. Average bicortical thickness was statistically correlated with femoral bone density values, with a 1-mm increase in average bicortical thickness associated with a 0.05 g/cm(2)-increase in femoral density. Average bicortical thickness was not associated with lumbar bone density. Conclusions Bicortical thickness of the distal radius was positively correlated with femoral bone density but not with lumbar spine density. This may reflect similarity in quality and loading properties of the femur and radius as appendicular bones, compared with the axial spine. Identification of thinned distal radial cortices in association with distal radius fracture is a simple qualitative observation that should prompt further evaluation with DXA and medical management of bone insufficiency. Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved. C1 Univ Connecticut, Dept Orthopaed Surg, Farmington, CT 06030 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Boston, MA 02215 USA. RP Wolf, JM (reprint author), Univ Connecticut, Ctr Hlth, New England Musculoskeletal Inst, Dept Orthopaed Surg, 263 Farmington Ave,MARB4 ORTHO, Farmington, CT 06030 USA. EM jmwolf@uchc.edu FU American Foundation for Surgery of the Hand; Orthopaedic Research and Education Foundation (RJOS/DePuy/OREF grant) FX Funding for this work was received from the American Foundation for Surgery of the Hand and the Orthopaedic Research and Education Foundation (RJOS/DePuy/OREF grant). The authors acknowledge the assistance of Katy Coyle, RN, Mark Cote, PhD, Lindsay Herder, BS, and Mary Bouxsein, PhD. NR 21 TC 5 Z9 5 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2015 VL 40 IS 3 BP 493 EP 499 DI 10.1016/j.jhsa.2014.12.015 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CD4CH UT WOS:000351029700012 PM 25708436 ER PT J AU Mellema, JJ Janssen, SJ Guitton, TG Ring, D AF Mellema, Jos J. Janssen, Stein J. Guitton, Thierry G. Ring, David TI Quantitative 3-Dimensional Computed Tomography Measurements of Coronoid Fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Coronoid; fracture; morphology; computed tomography; 3-dimensional ID SURFACE-AREA; RADIAL HEAD AB Purpose Using quantitative 3-dimensional computed tomography (Q3DCT) modeling, we tested the null hypothesis that there was no difference in fracture fragment volume, articular surface involvement, and number of fracture fragments between coronoid fracture types and patterns of traumatic elbow instability. Methods We studied 82 patients with a computed tomography scan of a coronoid fracture using Q3DCT modeling. Fracture fragments were identified and fragment volume and articular surface involvement were measured within fracture types and injury patterns. Kruskal Wallis test was used to evaluate the Q3DCT data of the coronoid fractures. Results Fractures of the coronoid tip (n = 45) were less fragmented and had the smallest fragment volume and articular surface area involvement compared with anteromedial facet fractures (n = 20) and base fractures (n = 17). Anteromedial facet and base fractures were more fragmented than tip fractures, and base fractures had the largest fragment volume and articular surface area involvement compared with tip and anteromedial facet fractures. We found similar differences between fracture types described by Regan and Morrey. Furthermore, fractures associated with terrible triad fracture dislocation ( n = 42) had the smallest fragment volume, and fractures associated with olecranon fracture dislocations (n = 17) had the largest fragment volume and articular surface area involvement compared with the other injury patterns. Conclusions Analyzing fractures of the coronoid using Q3DCT modeling demonstrated that fracture fragment characteristics differ significantly between fracture types and injury patterns. Detailed knowledge of fracture characteristics and their association with specific patterns of traumatic elbow instability may assist decision making and preoperative planning. Clinical relevance Quantitative 3DCT modeling can provide a more detailed understanding of fracture morphology, which might guide decision making and implant development. Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Univ Amsterdam, Acad Med Ctr, Orthotrauma Res Ctr Amsterdam, NL-1105 AZ Amsterdam, Netherlands. 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 Guitton, Thierry/0000-0002-2599-1985; Ring, David/0000-0002-6506-4879 NR 18 TC 8 Z9 8 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2015 VL 40 IS 3 BP 526 EP 533 DI 10.1016/j.jhsa.2014.07.059 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CD4CH UT WOS:000351029700018 PM 25510153 ER PT J AU Hanson, JT Leykum, LK Pugh, JA McDaniel, RR AF Hanson, Joshua T. Leykum, Luci K. Pugh, Jacqueline A. McDaniel, Reuben R. TI Nighttime Clinical Encounters: How Residents Perceive and Respond to Calls at Night SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID SIGN-OUT; HANDOFF PROGRAM; PATIENT-CARE; HEALTH-CARE; QUALITY; IMPROVEMENT AB BACKGROUNDCare fragmentation is common and contributes to communication errors and adverse events. Handoff tools were developed to reduce the potential for these errors. Despite their widespread adoption, there is little information describing their impact on clinical work. Understanding their impact could be helpful in improving handoffs and transitions. OBJECTIVETo better understand what clinical work is done overnight, the housestaff perceptions of overnight clinical work, and how handoff instruments support this work. DESIGNReal-time data collection and survey. PARTICIPANTSInternal medicine resident physicians. MAIN MEASURESData collection measured information related to nighttime clinical encounters, including the information sources and actions taken. Surveys assessed resident perceptions toward care transitions. KEY RESULTSOf 299 encounters, 289 contained complete data. The tool was used as an information source in 27.7% of encounters, whereas the information source was either the nurse or the chart in 94.4% of encounters. Many encounters resulted in a new order for a medication, whereas 3.8% resulted in documentation. In the survey data, 73.6% residents reported the sign-out procedure was safe. CONCLUSIONThese data suggest that a handoff tool is not sufficient to address nighttime clinical issues and suggest that effective care requires more than just the information transfer. It may also reflect that electronic medical records have become a readily available information source at the point of care. Sign-out should support residents' ability to make sense of what is happening and integrate care of day and night teams, rather than solely transfer information. Journal of Hospital Medicine 2015;10:142-146. 2015 Society of Hospital Medicine C1 [Hanson, Joshua T.; Leykum, Luci K.; Pugh, Jacqueline A.] South Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX USA. [Hanson, Joshua T.; Leykum, Luci K.; Pugh, Jacqueline A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Sch Med, San Antonio, TX 78229 USA. [McDaniel, Reuben R.] Univ Texas Austin, McCombs Sch Business, Dept Informat Risk & Operat Management, Austin, TX 78712 USA. RP Hanson, JT (reprint author), 7703 Floyd Curl Dr,MC 7982, San Antonio, TX 78229 USA. EM hansonj4@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [CDA 07-022]; South Texas Veterans Health Care System FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (CDA 07-022). Investigator salary support was provided through this funding, and through the South Texas Veterans Health Care System. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. Parts of these data were presented at the 2013 SGIM National Meeting in Denver, Colorado. The authors report no conflicts of interest. NR 24 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD MAR PY 2015 VL 10 IS 3 BP 142 EP 146 DI 10.1002/jhm.2315 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CC8XX UT WOS:000350653000002 PM 25736614 ER PT J AU Siegel, RS Hoeppner, B Yen, S Stout, RL Weinstock, LM Hower, HM Birmaher, B Goldstein, TR Goldstein, BI Hunt, JI Strober, M Axelson, DA Gill, MK Keller, MB AF Siegel, Rebecca S. Hoeppner, Bettina Yen, Shirley Stout, Robert L. Weinstock, Lauren M. Hower, Heather M. Birmaher, Boris Goldstein, Tina R. Goldstein, Benjamin I. Hunt, Jeffrey I. Strober, Michael Axelson, David A. Gill, Mary Kay Keller, Martin B. TI Longitudinal Associations Between Interpersonal Relationship Functioning and Mood Episode Severity in Youth With Bipolar Disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Bipolar disorder; interpersonal relationship functioning; longitudinal ID SPECTRUM DISORDERS; SOCIAL SUPPORT; I DISORDER; FOLLOW-UP; DEPRESSIVE SYMPTOMS; FIT INDEXES; ADOLESCENTS; CHILDREN; PHENOTYPE; COMORBIDITY AB This study examined the longitudinal association between mood episode severity and relationships in youth with bipolar (BP) disorder. Participants were 413 Course and Outcome of Bipolar Youth study youth, aged 12.6 +/- 3.3 years. Monthly ratings of relationships (parents, siblings, and friends) and mood episode severity were assessed by the Adolescent Longitudinal Interval Follow-up Evaluation Psychosocial Functioning Schedule and Psychiatric Rating Scales, on average, every 8.2months over 5.1 years. Correlations examined whether participants with increased episode severity also reported poorer relationships and whether fluctuations in episode severity predicted fluctuations in relationships, and vice versa. Results indicated that participants with greater mood episode severity also had worse relationships. Longitudinally, participants had largely stable relationships. To the extent that there were associations, changes in parental relationships may precede changes in episode severity, although the magnitude of this finding was small. Findings have implications for relationship interventions in BP youth. C1 [Siegel, Rebecca S.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Hoeppner, Bettina] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Addict Med, Cambridge, MA 02138 USA. [Yen, Shirley; Stout, Robert L.; Weinstock, Lauren M.; Hower, Heather M.; Hunt, Jeffrey I.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Providence, RI 02906 USA. [Yen, Shirley; Stout, Robert L.; Weinstock, Lauren M.; Hower, Heather M.; Keller, Martin B.] Butler Hosp, Providence, RI 02906 USA. [Birmaher, Boris; Goldstein, Tina R.; Gill, Mary Kay] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA. [Goldstein, Benjamin I.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Med Ctr, Dept Child Psychiat, Toronto, ON, Canada. [Hunt, Jeffrey I.] Emma Pendelton Bradley Hosp, East Providence, RI USA. [Strober, Michael] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Axelson, David A.] Nationwide Childrens Hosp, Columbus, OH USA. [Axelson, David A.] Ohio State Coll Med, Columbus, OH USA. RP Hower, HM (reprint author), Brown Univ, Dept Psychiat & Human Behav, Butler Hosp, 700 Butler Dr, Providence, RI 02906 USA. EM heather_hower@brown.edu OI Weinstock, Lauren/0000-0001-9970-235X FU NIMH [MH59691, MH059929, MH59977]; National Institute on Drug Abuse (NIDA) [K01DA027097] FX The authors thank the families for their participation and the COBY research staff and Shelli Avenevoli, PhD, from the National Institutes of Mental Health (NIMH) for their support. This article was supported by NIMH grants MH59691 (to Drs Keller/Yen), MH059929 (to Dr Birmaher), and MH59977 (to Dr Strober) and National Institute on Drug Abuse (NIDA) grant K01DA027097 (to Dr Hoeppner). NR 52 TC 0 Z9 0 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAR PY 2015 VL 203 IS 3 BP 194 EP 204 DI 10.1097/NMD.0000000000000261 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CD0JW UT WOS:000350759600008 PM 25668652 ER PT J AU Wright, JA Whiteley, JA Laforge, RG Adams, WG Berry, D Friedman, RH AF Wright, Julie A. Whiteley, Jessica A. Laforge, Robert G. Adams, William G. Berry, Donna Friedman, Robert H. TI Validation of 5 Stage-of-Change Measures for Parental Support of Healthy Eating and Activity SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE readiness; measures; parents; nutrition; television; stages of change; sugar-sweetened beverage; obesity ID PHYSICAL-ACTIVITY; BEHAVIOR-CHANGE; TRANSTHEORETICAL MODEL; SELF-EFFICACY; VEGETABLE CONSUMPTION; DECISIONAL BALANCE; EXERCISE BEHAVIOR; CHILDREN; ADOLESCENTS; OVERWEIGHT AB Objective: To assess the validity of 5 parental stage-of-change (SOC) measures: (1) providing 5 servings/d of fruits and vegetables (FV), (2) limiting television (TV) to 2 h/d, (3) helping children achieve 1 h/d physical activity (PA), (4) limiting sugary drinks (SD) to 1 serving/wk, and (5) limiting fruit juice (FJ) to 4-6 oz/d. Design: Cross-sectional instrument development study. Construct validity was evaluated by examining whether parental self-efficacy, parental readiness ladder (ladder), and child's behavioral levels (eg, FV consumption) exhibited a theoretically consistent pattern across the SOC. Setting/Participants: Convenience sample (n = 283) of parents of children aged 4-10 years. Measures: Survey assessed SOC, ladder, and child's behavioral level score for each topic (FV, TV, PA, SD, and FJ), and parental self-efficacy for measure except TV. Analysis: Analysis of variance with Tukey-Kramer post hoc tests examined whether variables differed by SOC. Results: Percentages of parents in the pre-action SOC were 34% (PA), 39% (FV), 42% (SD), 45% (TV), and 63% (FJ). Parental self-efficacy, ladder, and child's behavioral level differed significantly by SOC for each topic area (P < .001). Maintenance SOC was significantly higher than pre-action SOC. Conclusions and Implications: Measured variables exhibited a theoretically consistent pattern across SOC, suggesting construct validity and potential usefulness for obesity prevention efforts. C1 [Wright, Julie A.; Whiteley, Jessica A.] Univ Massachusetts, Dept Exercise & Hlth Sci, Boston, MA 02125 USA. [Wright, Julie A.; Friedman, Robert H.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Adams, William G.] Boston Univ, Sch Med, Dept Gen Pediat, Boston, MA 02118 USA. [Berry, Donna] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Laforge, Robert G.] Univ Rhode Isl, Dept Psychol, Kingston, RI 02881 USA. RP Wright, JA (reprint author), Univ Massachusetts, Dept Exercise & Hlth Sci, 100 Morrissey Blvd, Boston, MA 02125 USA. EM julie.wright@umb.edu OI Wright, Julie/0000-0002-5115-7011 FU National Cancer Institute [K07CA113643] FX This study was supported by a grant from the National Cancer Institute (K07CA113643). NR 37 TC 1 Z9 1 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 EI 1878-2620 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD MAR-APR PY 2015 VL 47 IS 2 BP 134 EP 142 DI 10.1016/j.jneb.2014.11.003 PG 9 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA CD1HO UT WOS:000350825900007 PM 25579067 ER PT J AU Kutney-Lee, A Brennan, CW Meterko, M Ersek, M AF Kutney-Lee, Ann Brennan, Caitlin W. Meterko, Mark Ersek, Mary TI Organization of Nursing and Quality of Care for Veterans at the End of Life SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Nursing care; palliative care; veterans; quality of care; end-of-life care; Department of Veterans Affairs ID PRACTICE ENVIRONMENT SCALE; CROSS-SECTIONAL SURVEYS; PATIENT SATISFACTION; FAMILY ASSESSMENT; HOSPITAL-CARE; UNITED-STATES; WORK INDEX; NATIONWIDE; OUTCOMES; PERSPECTIVES AB Context. The Veterans Health Administration (VA) has improved the quality of end-of-life (EOL) care over the past several years. Several structural and process variables are associated with better outcomes. Little is known, however, about the relationship between the organization of nursing care and EOL outcomes. Objectives. To examine the association between the organization of nursing care, including the nurse work environment and nurse staffing levels, and quality of EOL care in VA acute care facilities. Methods. Secondary analysis of linked data from the Bereaved Family Survey (BFS), electronic medical record, administrative data, and the VA Nursing Outcomes Database. The sample included 4908 veterans who died in one of 116 VA acute care facilities nationally between October 2010 and September 2011. Unadjusted and adjusted generalized estimating equations were used to examine associations between nursing and BFS outcomes. Results. BFS respondents were 17% more likely to give an excellent overall rating of the quality of EOL care received by the veteran in facilities with better nurse work environments (P <= 0.05). The nurse work environment also was a significant predictor of providers listening to concerns and providing desired treatments. Nurse staffing was significantly associated with an excellent overall rating, alerting of the family before death, attention to personal care needs, and the provision of emotional support after the patient's death. Conclusion. Improvement of the nurse work environment and nurse staffing in VA acute care facilities may result in enhanced quality of care received by hospitalized veterans at the EOL. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Kutney-Lee, Ann; Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Kutney-Lee, Ann; Ersek, Mary] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Brennan, Caitlin W.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Meterko, Mark] VA Boston Healthcare Syst, Boston, MA USA. [Meterko, Mark] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Kutney-Lee, A (reprint author), Univ Penn, Sch Nursing, 418 Curie Blvd,Claire M Fagin Hall,Room 385, Philadelphia, PA 19104 USA. EM akutney@nursing.upenn.edu FU VA National Quality Scholars Program; NINR (Aiken, PI) [R01-NR-004513]; Robert Wood Johnson Foundation FX Dr. Brennan was supported by the VA National Quality Scholars Program. This work also was supported by NINR R01-NR-004513 (Aiken, PI) and the Robert Wood Johnson Foundation. The opinions expressed in this article are those of the authors alone and do not necessarily reflect the views of the Department of Veterans Affairs, National Institutes of Health, Public Health Service, Department of Health and Human Services, or the Robert Wood Johnson Foundation. The authors declare no conflicts of interest. NR 32 TC 3 Z9 3 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAR PY 2015 VL 49 IS 3 BP 570 EP 577 DI 10.1016/j.jpainsymman.2014.07.002 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CD2JN UT WOS:000350903800013 PM 25116912 ER PT J AU Becker, G Jors, K Block, S AF Becker, Gerhild Jors, Karin Block, Susan TI Discovering the Truth Beyond the Truth SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Truth disclosure; physician-patient relations; personal autonomy ID PATIENT AB The question "What is truth?'' is one of the oldest questions in philosophy. Truth within the field of medicine has gained relevance because of its fundamental relationship to the principle of patient autonomy. To fully participate in their medical care, patients must be told the truth-even in the most difficult of situations. Palliative care emphasizes patient autonomy and a patient-centered approach, and it is precisely among patients with chronic, life-threatening, or terminal illnesses that truth plays a particularly crucial role. For these patients, finding out the truth about their disease forces them to confront existential fears. As physicians, we must understand that truth, similar to the complexity of pain, is multidimensional. In this article, we discuss the truth from three linguistic perspectives: the Latin veritas, the Greek aletheia, and the Hebrew emeth. Veritas conveys an understanding of truth focused on facts and reality. Aletheia reveals truth as a process, and emeth shows that truth is experienced in truthful encounters with others. In everyday clinical practice, truth is typically equated with the facts. However, this limited understanding of the truth does not account for the uniqueness of each patient. Although two patients may receive the same diagnosis (or facts), each will be affected by this truth in a very individual way. To help patients apprehend the truth, physicians are called to engage in a delicate back-and-forth of multiple difficult conversations in which each patient is accepted as a unique individual. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Becker, Gerhild; Jors, Karin] Univ Med Ctr Freiburg, Dept Palliat Care, Ctr Comprehens Canc, D-79106 Freiburg, Germany. [Block, Susan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Jors, K (reprint author), Univ Med Ctr Freiburg, Dept Palliat Care, Robert Koch Str 3, D-79106 Freiburg, Germany. EM karin.jors@uniklinik-freiburg.de OI Becker, Gerhild/0000-0001-9060-0285 NR 9 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAR PY 2015 VL 49 IS 3 BP 646 EP 649 DI 10.1016/j.jpainsymman.2014.10.016 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CD2JN UT WOS:000350903800021 PM 25542549 ER PT J AU Singh, JA Dalbeth, N AF Singh, Jasvinder A. Dalbeth, Nicola TI Is the Double Contour Sign Specific for Gout? Or Only for Crystal Arthritis? SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID ASYMPTOMATIC HYPERURICEMIA; ULTRASOUND; DEPOSITION; INVOLVEMENT; DIAGNOSIS C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Dalbeth, Nicola] Univ Auckland, Auckland 1, New Zealand. [Dalbeth, Nicola] Auckland Dist Hlth Board, Auckland, New Zealand. RP Singh, JA (reprint author), Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham VA Med Ctr, Birmingham, AL 35233 USA. NR 8 TC 1 Z9 1 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2015 VL 42 IS 3 BP 353 EP 354 DI 10.3899/jrheum.141322 PG 2 WC Rheumatology SC Rheumatology GA CD0FM UT WOS:000350746000003 PM 25729038 ER PT J AU Greenberg, PL Stone, RM Bejar, R Bennett, JM Bloomfield, CD Borate, U De Castro, CM Deeg, HJ DeZern, AE Fathi, AT Frankfurt, O Gaensler, K Garcia-Manero, G Griffiths, EA Head, D Klimek, V Komrokji, R Kujawski, LA Maness, LJ O'Donnell, MR Pollyea, DA Scott, B Shami, PJ Stein, BL Westervelt, P Wheeler, B Shead, DA Smith, C AF Greenberg, Peter L. Stone, Richard M. Bejar, Rafael Bennett, John M. Bloomfield, Clara D. Borate, Uma De Castro, Carlos M. Deeg, H. Joachim DeZern, Amy E. Fathi, Amir T. Frankfurt, Olga Gaensler, Karin Garcia-Manero, Guillermo Griffiths, Elizabeth A. Head, David Klimek, Virginia Komrokji, Rami Kujawski, Lisa A. Maness, Lori J. O'Donnell, Margaret R. Pollyea, Daniel A. Scott, Bart Shami, Paul J. Stein, Brady L. Westervelt, Peter Wheeler, Benton Shead, Dorothy A. Smith, Courtney TI Myelodysplastic Syndromes, Version 2.2015 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PROGNOSTIC SCORING SYSTEM; ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; TRANSFUSION-DEPENDENT PATIENTS; CLINICAL-PRACTICE GUIDELINE; BLOOD-CELL TRANSFUSION; CHROMOSOME 5Q DELETION; DISEASE PROGRESSION; SETBP1 MUTATIONS; SYNDROMES MDS AB The NCCN Guidelines for Myelodysplastic Syndromes (MDS) comprise a heterogeneous group of myeloid disorders with a highly variable disease course that depends largely on risk factors. Risk evaluation is therefore a critical component of decision-making in the treatment of MDS. The development of newer treatments and the refinement of current treatment modalities are designed to improve patient outcomes and reduce side effects. These NCCN Guidelines Insights focus on the recent updates to the guidelines, which include the incorporation of a revised prognostic scoring system, addition of molecular abnormalities associated with MDS, and refinement of treatment options involving a discussion of cost of care. C1 [Greenberg, Peter L.] Stanford Canc Inst, Stanford, CA 94305 USA. [Stone, Richard M.] Dana FarberBrigham & Womens Canc Ctr, Boston, MA 02115 USA. [Bejar, Rafael] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA USA. [Bennett, John M.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bloomfield, Clara D.] Solove Res Inst, Columbus, OH USA. [Borate, Uma] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [De Castro, Carlos M.] Duke Canc Inst, Durham, NC USA. [Deeg, H. Joachim; Scott, Bart] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [DeZern, Amy E.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Fathi, Amir T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Frankfurt, Olga; Stein, Brady L.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Gaensler, Karin] UCSF, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Griffiths, Elizabeth A.] Roswell Pk Canc Inst, Buffalo, NY USA. [Head, David] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Klimek, Virginia] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Komrokji, Rami] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Kujawski, Lisa A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Maness, Lori J.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [O'Donnell, Margaret R.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Pollyea, Daniel A.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Shami, Paul J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Westervelt, Peter] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Westervelt, Peter] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Wheeler, Benton] Univ Tennessee, St Jude Childrens Res Hosp, Ctr Hlth Sci, Knoxville, TN 37996 USA. [Shead, Dorothy A.; Smith, Courtney] Natl Comprehens Canc Network, Ft Washington, PA USA. RP Greenberg, PL (reprint author), Stanford Canc Inst, Stanford, CA 94305 USA. FU Eisai; Exelixis Inc.; 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 59 TC 15 Z9 15 U1 1 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2015 VL 13 IS 3 BP 261 EP 272 PG 12 WC Oncology SC Oncology GA CD0RN UT WOS:000350781700004 PM 25736003 ER PT J AU Jacobson, CA Freedman, AS AF Jacobson, Caron A. Freedman, Arnold S. TI Is Observation Dead in Follicular Lymphoma? Still Appropriate SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ADVANCED-STAGE; RITUXIMAB; TRIAL; CYCLOPHOSPHAMIDE; VINCRISTINE; PREDNISONE; THERAPY; POLICY; WATCH AB Given the incurable yet indolent nature of follicular lymphoma (FL) and the lack of a survival benefit seen with the early treatment of patients with a low tumor burden, watchful waiting has been the predominant strategy for treating asymptomatic patients with newly diagnosed FL for more than 2 decades. The success and tolerability of rituximab for the treatment of this disease, however, has led to challenges for this treatment paradigm and the consideration of early upfront treatment with rituximab monotherapy, with or without rituximab maintenance. These strategies have resulted in improvements in quality of life with a low incidence of toxicity and have led some to practice changes. However, based on uncertainty about how early treatment affects response to second treatment, the differential cost of treatment, and the lack of a survival benefit, observation remains an appropriate and viable strategy for select patients. C1 [Jacobson, Caron A.; Freedman, Arnold S.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Arnold_Freedman@dfci.harvard.edu NR 10 TC 1 Z9 1 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 MAR PY 2015 VL 13 IS 3 BP 367 EP 370 PG 4 WC Oncology SC Oncology GA CD0RN UT WOS:000350781700013 PM 25736012 ER PT J AU Steensma, DP AF Steensma, David P. TI Mimicking MacGyver in the Oncology Clinic: Improvisation and Creative Solutions, Only Rarely Involving Duct Tape SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Steensma, David P.] Dana Farber Canc Inst, Dept Hematol Malignancies, Adult Leukemia Grp, Boston, MA 02115 USA. [Steensma, David P.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Steensma, DP (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2015 VL 13 IS 3 BP 371 EP 373 PG 3 WC Oncology SC Oncology GA CD0RN UT WOS:000350781700014 PM 25736013 ER PT J AU Fox, N Schwartz, D Salazar, JH Haut, ER Dahm, P Black, JH Brakenridge, SC Como, JJ Hendershot, K King, DR Maung, AA Moorman, ML Nagy, K Petrey, LB Tesoriero, R Scalea, TM Fabian, TC AF Fox, Nicole Schwartz, Diane Salazar, Jose H. Haut, Elliott R. Dahm, Philipp Black, James H. Brakenridge, Scott C. Como, John J. Hendershot, Kimberly King, David R. Maung, Adrian A. Moorman, Matthew L. Nagy, Kimberly Petrey, Laura B. Tesoriero, Ronald Scalea, Thomas M. Fabian, Timothy C. TI Evaluation and Management of Blunt Traumatic Aortic Injury: A Practice Management Guideline From the Eastern Association for the Surgery of Trauma SO JOURNAL OF TRAUMA NURSING LA English DT Article DE Blunt injury; Traumatic aortic injury; Blunt aortic trauma ID CHEST COMPUTED-TOMOGRAPHY; DESCENDING THORACIC AORTA; ENDOVASCULAR STENT-GRAFTS; SINGLE-CENTER EXPERIENCE; OPEN REPAIR; DELAYED REPAIR; AMERICAN-ASSOCIATION; CONTAINED RUPTURE; OPERATIVE REPAIR; SURGICAL REPAIR AB Background: Blunt traumatic aortic injury (BTAI) is the second most common cause of death in trauma patients. Eighty percent of patients with BTAI will die before reaching a trauma center. The issues of how to diagnose, treat, and manage BTAI were first addressed by the Eastern Association for the Surgery of Trauma (EAST) in the practice management guidelines on this topic published in 2000. Since that time, there have been advances in the management of BTAI. As a result, the EAST guidelines committee decided to develop updated guidelines for this topic using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework recently adopted by EAST. Methods: A systematic review of the MEDLINE database using PubMed was performed. The search retrieved English language articles regarding BTAI from 1998 to 2013. Letters to the editor, case reports, book chapters, and review articles were excluded. Topics of investigation included imaging to diagnose BTAI. type of operative repair, and timing of operative repair. Results: Sixty articles were identified. Of these. 51 articles were selected to construct the guidelines. Conclusion: There have been changes in practice since the publication of the previous guidelines in 2000. Computed tomography of the chest with intravenous contrast is strongly recommended to diagnose clinically significant BTAI. Endovascular repair is strongly recommended for patients without contraindications. Delayed repair of BTAI is suggested, with the stipulation that effective blood pressure control must be used in these patients. (J Trauma Acute Care Surg. 2015;78: 125-135. Level of Evidence: Systematic reviews and meta-analyses, level III. C1 [Fox, Nicole] Rowan Univ, Cooper Med Sch, Cooper Univ Hosp, Dept Surg, Camden, NJ USA. [Schwartz, Diane] Johns Hopkins Bayview Med Ctr, Dept Surg, Baltimore, MD USA. [Haut, Elliott R.] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. [Black, James H.] Johns Hopkins Univ Hosp, Dept Vasc Surg & Endovasc Therapy, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Baltimore, MD USA. [Tesoriero, Ronald; Scalea, Thomas M.] Univ Maryland, Sch Med, Dept Surg, R Adams Cowley Shock Trauma Ctr, Baltimore, MD 21201 USA. [Dahm, Philipp] Univ Florida, Coll Med, Dept Urol, Malcom Randall VAMC, Gainesville, FL 32611 USA. [Brakenridge, Scott C.] Univ Florida, Dept Surg, Hlth Sci Ctr, UF Hlth Shands Hosp, Gainesville, FL USA. [Como, John J.] Metrohlth Med Ctr, Dept Surg, Cleveland, OH USA. [Moorman, Matthew L.] Cleveland Clin, Lerner Coll Med, Div Acute Care Surg, Cleveland, OH USA. Wright State Univ, Dept Surg, Boonshoft Sch Med, Dayton, OH 45435 USA. [King, David R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Maung, Adrian A.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Nagy, Kimberly] Stroger Hosp, Cook Cty Trauma Unit, Dept Surg, Chicago, IL USA. [Petrey, Laura B.] Baylor Univ, Med Ctr, Dept Surg, Dallas, TX 75246 USA. [Fabian, Timothy C.] Univ Tennessee, Hlth Sci Ctr, Dept Surg, Memphis, TN USA. RP Fox, N (reprint author), Cooper Univ Hosp, Trauma, Crit Care, Emergency Surg, 1 Cooper Plaza, Camden, NJ 08103 USA. EM fox-nicoleo@cooperhealth.edu OI King, David/0000-0003-1028-1478; Brakenridge, Scott/0000-0002-7327-3718 NR 57 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-7496 EI 1932-3883 J9 J TRAUMA NURS JI J. Trauma Nurs. PD MAR-APR PY 2015 VL 22 IS 2 BP 99 EP 110 DI 10.1097/JTN.0000000000000118 PG 12 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA CD3SR UT WOS:000351001500010 PM 25768967 ER PT J AU Oklu, R Ghasemi-Rad, M Irani, Z Brinegar, KN Toner, E Hirsch, JA AF Oklu, Rahmi Ghasemi-Rad, Mohammad Irani, Zubin Brinegar, Katelyn N. Toner, Emre Hirsch, Joshua A. TI Aspiration Thrombectomy Using the Penumbra Catheter SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter ID STROKE; SYSTEM C1 [Oklu, Rahmi; Ghasemi-Rad, Mohammad; Irani, Zubin; Brinegar, Katelyn N.; Toner, Emre] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Intervent Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Intervent Neuroradiol, Boston, MA 02114 USA. RP Oklu, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Intervent Radiol, Gray Bigelow 290,55 Fruit St, Boston, MA 02114 USA. NR 4 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR PY 2015 VL 26 IS 3 BP 454 EP 455 DI 10.1016/j.jvir.2014.11.028 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CD1KO UT WOS:000350834000026 PM 25735532 ER PT J AU Hughes, KS Schnaper, LA AF Hughes, Kevin S. Schnaper, Lauren A. TI Can older women with early breast cancer avoid radiation? SO LANCET ONCOLOGY LA English DT Editorial Material ID INTRAOPERATIVE RADIOTHERAPY; FOLLOW-UP; TRIAL; IRRADIATION; IMPACT C1 [Hughes, Kevin S.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. [Hughes, Kevin S.] Harvard Univ, Sch Med, Boston, MA USA. [Schnaper, Lauren A.] Greater Baltimore Med Ctr, Baltimore, MD USA. RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. EM kshughes@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 11 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2015 VL 16 IS 3 BP 235 EP 237 DI 10.1016/S1470-2045(15)70014-8 PG 4 WC Oncology SC Oncology GA CC7WA UT WOS:000350577900031 PM 25637341 ER PT J AU Gray, PJ Zietman, AL AF Gray, Phillip J. Zietman, Anthony L. TI Androgen deprivation with radiotherapy: how long is long enough? SO LANCET ONCOLOGY LA English DT Editorial Material ID PROSTATE-CANCER; RADIATION-THERAPY; TRIAL; SUPPRESSION; DURATION C1 [Gray, Phillip J.; Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02138 USA. RP Gray, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02138 USA. EM pjgray@partners.org NR 11 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 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2015 VL 16 IS 3 BP 244 EP 246 DI 10.1016/S1470-2045(15)70073-2 PG 4 WC Oncology SC Oncology GA CC7WA UT WOS:000350577900037 PM 25702877 ER PT J AU Ko, JJ Xie, WL Kroeger, N Lee, JL Rini, BI Knox, JJ Bjarnason, GA Srinivas, S Pal, SK Yuasa, T Smoragiewicz, M Donskov, F Kanesvaran, R Wood, L Ernst, DS Agarwal, N Vaishampayan, UN Rha, SY Choueiri, TK Heng, DYC AF Ko, Jenny J. Xie, Wanling Kroeger, Nils Lee, Jae-Lyun Rini, Brian I. Knox, Jennifer J. Bjarnason, Georg A. Srinivas, Sandy Pal, Sumanta K. Yuasa, Takeshi Smoragiewicz, Martin Donskov, Frede Kanesvaran, Ravindran Wood, Lori Ernst, D. Scott Agarwal, Neeraj Vaishampayan, Ulka N. Rha, Sun-young Choueiri, Toni K. Heng, Daniel Y. C. TI International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study SO LANCET ONCOLOGY LA English DT Article ID RANDOMIZED PHASE-3 TRIAL; DOUBLE-BLIND; III TRIAL; SURVIVAL; SORAFENIB; CANCER; SUNITINIB; PROGRESSION; EVEROLIMUS; PAZOPANIB AB Background Previous prognostic models for second-line systemic therapy in patients with metastatic renal cell carcinoma have not been studied in the setting of targeted therapy. We sought to validate the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in patients with metastatic renal cell carcinoma receiving next-line targeted therapy after progression on first-line targeted therapy. Methods In this population-based study, we analysed patients who received second-line targeted therapy for metastatic renal cell carcinoma at 19 centres in Canada, USA, Greece, Japan, Singapore, South Korea, and Denmark. The primary endpoint was overall survival since the initiation of second-line therapy. We compared the prognostic performance of the IMDC model with the three-factor MSKCC model used for previously treated patients for overall survival since the start of second-line targeted therapy. Findings Between Jan 1, 2005, and Nov 30, 2012, we included 1021 patients treated with second-line targeted therapy. Median overall survival since the start of second-line targeted therapy was 12.5 months (95% CI 11.3-14.3). Five of six predefined factors in the IMDC model (anaemia, thrombocytosis, neutrophilia, Karnofsky performance status [KPS] <80, and <1 year from diagnosis to first-line targeted therapy) were independent predictors of poor overall survival on multivariable analysis. The concordance index using all six prognostic factors (ie, also including hypercalcaemia) was 0.70 (95% CI 0.67-0.72) with the IMDC model and was 0.66 (95% CI 0.64-0.68) with the three-factor MSKCC model. When patients were divided into three risk categories using IMDC criteria, median overall survival was 35.3 months (95% CI 28.3-47.8) in the favourable risk group (n=76), 16.6 months (14.9-17.9) in the intermediate risk group (n=529), and 5.4 months (4.7-6.8) in the poor risk group (n=261). Interpretation The IMDC prognostic model can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in fi rst-line targeted therapy. The IMDC prognostic model in the second-line targeted therapy setting has an improved prognostic performance and is applicable to a more contemporary patient cohort than that of the three-factor MSKCC model. C1 [Ko, Jenny J.; Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Dept Med Oncol, Calgary, AB T2N 4N2, Canada. [Xie, Wanling; Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kroeger, Nils] Ernst Moritz Arndt Univ Greifswald, Dept Urol, Univ Hosp Greifswald, Greifswald, Germany. [Lee, Jae-Lyun] Univ Ulsan, Coll Med, Dept Oncol, Asan Med Ctr, Seoul, South Korea. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Knox, Jennifer J.] Univ Toronto, Princess Margaret Canc Ctr, Dept Med Oncol, Univ Hlth Network, Toronto, ON, Canada. [Bjarnason, Georg A.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Srinivas, Sandy] Stanford Med Ctr, Div Oncol, Stanford, CA USA. [Pal, Sumanta K.] City Hope Comprehens Canc Ctr, Med Oncol & Expt Therapeut, Duarte, CA USA. [Yuasa, Takeshi] Japanese Fdn Canc Res, Dept Urol, Canc Inst Hosp, Tokyo, Japan. [Smoragiewicz, Martin] Univ British Columbia, British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 1M9, Canada. [Donskov, Frede] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [Kanesvaran, Ravindran] Natl Canc Ctr Singapore, Div Med Oncol, Singapore, Singapore. [Wood, Lori] Dalhousie Univ, Queen Elizabeth II Hlth Sci Ctr, Halifax, NS, Canada. [Ernst, D. Scott] London Reg Canc Ctr, London, ON N6A 4L6, Canada. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Vaishampayan, Ulka N.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Rha, Sun-young] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, Alberta Hlth Serv Canc Care, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca FU DF/HCC Kidney Cancer SPORE [P50 CA101942-01]; Kidney Cancer Research Network of Canada; Canadian Institute for Health Research; Trust Family FX DF/HCC Kidney Cancer SPORE P50 CA101942-01, Kidney Cancer Research Network of Canada, Canadian Institute for Health Research, Trust Family, Loker Pinard, Michael Brigham, and Gerald DeWulf. NR 31 TC 42 Z9 43 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2015 VL 16 IS 3 BP 293 EP 300 DI 10.1016/S1470-2045(14)71222-7 PG 8 WC Oncology SC Oncology GA CC7WA UT WOS:000350577900050 PM 25681967 ER PT J AU Penson, RT Huang, HQ Wenzel, LB Monk, BJ Stockman, S Long, HJ Ramondetta, LM Landrum, LM Oaknin, A Reid, TJA Leitao, MM Method, M Michael, H Tewari, KS AF Penson, Richard T. Huang, Helen Q. Wenzel, Lari B. Monk, Bradley J. Stockman, Sharon Long, Harry J., III Ramondetta, Lois M. Landrum, Lisa M. Oaknin, Ana Reid, Thomas J. A. Leitao, Mario M. Method, Michael Michael, Helen Tewari, Krishnansu S. TI Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240) SO LANCET ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; CLINICAL-TRIALS; UTERINE CERVIX; STAGE IVB; III TRIAL; CISPLATIN; CARCINOMA; SURVIVAL; CHEMOTHERAPY; VALIDATION AB Background GOG 240 was a practice-changing randomised phase 3 trial that concluded that chemotherapy plus bevacizumab for advanced cervical cancer significantly improves overall and progression-free survival, and the proportion of patients achieving an overall objective response, compared with chemotherapy alone. In this study, we aimed to analyse patient-reported outcomes in GOG 240. Methods Eligible adult participants (aged >= 18 years) had primary stage IVB or recurrent or persistent carcinoma of the cervix with measurable disease and GOG performance status of 0-1. Participants were randomly assigned by web-based permuted block randomisation (block size 4) in a 1: 1: 1: 1 ratio to the four treatment groups: cisplatin (50 mg/m(2) intravenously on day 1 or 2 of the treatment cycle) and paclitaxel (135 mg/m(2) intravenously over 24 h or 175 mg/m(2) intravenously over 3 h on day 1), with or without bevacizumab (15 mg/kg intravenously on day 1 or 2), or paclitaxel (175 mg/m(2) over 3 h on day 1) and topotecan (0.75 mg/m(2) for 30 min on days 1-3) with or without bevacizumab (15 mg/kg intravenously on day 1). Treatment assignment was concealed at randomisation (everyone was masked to treatment assignment, achieved by the use of a computer encrypted numbering system at the National Cancer Institute) and became open-label when each patient was registered to the trial. Treatment cycles were repeated every 21 days until disease progression or unacceptable toxicity, whichever occurred first. The coprimary endpoints of the trial were overall survival and safety; the primary quality-of-life endpoint was the score on the Functional Assessment of Cancer Therapy-Cervix Trial Outcome Index (FACT-Cx TOI). For our analysis of patient-reported outcomes, participants were assessed before treatment cycles 1, 2, and 5, and at 6 and 9 months after the start of cycle 1, with the FACT-Cx TOI, items from the FACT-GOG-Neurotoxicity subscale, and a worst pain item from the Brief Pain Inventory. All patients who completed baseline quality-of-life assessments and at least one further follow-up assessment were evaluable for quality-of-life outcomes. This study is registered with ClinicalTrials.gov, number NCT00803062. Findings Between April 6, 2009, and Jan 3, 2012, a total of 452 patients were enrolled in the trial, of whom 390 completed baseline quality-of-life assessment and at least one further assessment and were therefore evaluable for quality-of-life outcomes. In these patients, patient-reported outcome completion declined from 426 (94%) of 452 (at baseline) to 193 (63%) of 307 (9 months post-cycle 1), but completion rates did not differ significantly between treatment regimens (p=0.78). The baseline FACT-Cx TOI scores did not differ significantly between patients who received bevacizumab versus those who did not (p=0.27). Compared with patients who received chemotherapy alone, patients who received chemotherapy plus bevacizumab reported FACT-Cx TOI scores that were an average of 1 . 2 points lower (98 .75% CI -4.1 to 1.7; p=0.30). Interpretation Improvements in overall survival and progression-free survival attributed to the incorporation of bevacizumab into the treatment of advanced cervical cancer were not accompanied by any significant deterioration in health-related quality of life. Patients responding to anti-angiogenesis therapy who maintain an acceptable quality of life could be suitable at progression for treatment with other novel therapies that might confer additional benefit. C1 [Penson, Richard T.] Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. [Huang, Helen Q.] Roswell Pk Canc Inst, NRG Oncol Gynecol Oncol Grp, Buffalo, NY 14263 USA. [Wenzel, Lari B.; Tewari, Krishnansu S.] Univ Calif Irvine, Med Ctr, Orange, CA USA. [Monk, Bradley J.] Univ Arizona, Ctr Canc, Phoenix, AZ USA. [Monk, Bradley J.] Creighton Univ, St Josephs Hosp & Med Ctr, Phoenix, AZ USA. [Stockman, Sharon] Univ Iowa Hosp, Iowa City, IA USA. [Long, Harry J., III] Mayo Clin, Rochester, MN USA. [Ramondetta, Lois M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Landrum, Lisa M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Oaknin, Ana] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. [Reid, Thomas J. A.] Univ Cincinnati, Coll Med, Womens Canc Ctr Kettering, Kettering, OH USA. [Leitao, Mario M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Method, Michael] Michiana Hematol Oncol PC Mishawaka, Mishawaka, IN USA. [Michael, Helen] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, 55 Fruit St,Yawkey 9-064 9E, Boston, MA 02114 USA. EM rpenson@partners.org FU National Institutes of Health FX National Institutes of Health. NR 26 TC 24 Z9 25 U1 0 U2 5 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 MAR PY 2015 VL 16 IS 3 BP 301 EP 311 DI 10.1016/S1470-2045(15)70004-5 PG 11 WC Oncology SC Oncology GA CC7WA UT WOS:000350577900051 PM 25638326 ER PT J AU Armenian, SH Hudson, MM Mulder, RL Chen, MH Constine, LS Dwyer, M Nathan, PC Tissing, WJE Shankar, S Sieswerda, E Skinner, R Steinberger, J van Dalen, EC van der Pal, H Wallace, WH Levitt, G Kremer, LCM AF Armenian, Saro H. Hudson, Melissa M. Mulder, Renee L. Chen, Ming Hui Constine, Louis S. Dwyer, Mary Nathan, Paul C. Tissing, Wim J. E. Shankar, Sadhna Sieswerda, Elske Skinner, Rod Steinberger, Julia van Dalen, Elvira C. van der Pal, Helena Wallace, W. Hamish Levitt, Gill Kremer, Leontien C. M. TI Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group SO LANCET ONCOLOGY LA English DT Review ID TERM-FOLLOW-UP; LEFT-VENTRICULAR DYSFUNCTION; AMERICAN-HEART-ASSOCIATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; BONE-MARROW-TRANSPLANTATION; CARDIOVASCULAR RISK-FACTORS; ACC/AHA 2005 GUIDELINES; NT-PRO-BNP; LONG-TERM AB Survivors of childhood cancer treated with anthracycline chemotherapy or chest radiation are at an increased risk of developing congestive heart failure. In this population, congestive heart failure is well recognised as a progressive disorder, with a variable period of asymptomatic cardiomyopathy that precedes signs and symptoms. As a result, several clinical practice guidelines have been developed independently to help with detection and treatment of asymptomatic cardiomyopathy. These guidelines differ with regards to definitions of at-risk populations, surveillance modality and frequency, and recommendations for interventions. Differences between these guidelines could hinder the effective implementation of these recommendations. We report on the results of an international collaboration to harmonise existing cardiomyopathy surveillance recommendations using an evidence-based approach that relied on standardised definitions for outcomes of interest and transparent presentation of the quality of the evidence. The resultant recommendations were graded according to the quality of the evidence and the potential benefit gained from early detection and intervention. C1 [Armenian, Saro H.] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA USA. [Hudson, Melissa M.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Hudson, Melissa M.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Mulder, Renee L.; Sieswerda, Elske; van Dalen, Elvira C.; Kremer, Leontien C. M.] Emma Childrens Hosp, Acad Med Ctr, Dept Pediat Oncol, Amsterdam, Netherlands. [Chen, Ming Hui] Harvard Univ, Sch Med, Dept Pediat, Boston Childrens Hosp, Boston, MA 02115 USA. [Chen, Ming Hui] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Constine, Louis S.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. [Constine, Louis S.] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA. [Dwyer, Mary] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Nathan, Paul C.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Nathan, Paul C.] Univ Toronto, Dept Pediat, Toronto, ON, Canada. [Nathan, Paul C.] Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Tissing, Wim J. E.] Univ Groningen, Univ Med Ctr Groningen, Div Pediat Oncol & Pediat Hematol, Beatrix Childrens Hosp, Groningen, Netherlands. [Shankar, Sadhna] Childrens Natl Med Ctr, Div Oncol, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. [Skinner, Rod] Great North Childrens Hosp, Dept Paediat & Adolescent Haematol Oncol, Newcastle Upon Tyne, Tyne & Wear, England. [Skinner, Rod] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Steinberger, Julia] Univ Minnesota, Dept Pediat, Div Cardiol, Amplatz Childrens Hosp, Minneapolis, MN 55455 USA. [van der Pal, Helena] Emma Childrens Hosp, Dept Pediat Oncol & Med Oncol, Acad Med Ctr, Amsterdam, Netherlands. [Wallace, W. Hamish] Royal Hosp Sick Children, Dept Hematol Oncol, Edinburgh EH9 1LF, Midlothian, Scotland. [Levitt, Gill] Great Ormond St Hosp Sick Children, Dept Oncol Haematol, London WC1N 3JH, England. RP Armenian, SH (reprint author), Dept Populat Sci, City Hope 1500 East Duarte Rd, Duarte, CA 91010 USA. EM sarmenian@coh.org FU National Institutes of Health (NCI) [2 K12 CA001727-14, 1 U10 CA098543]; National Cancer Institute [CA 21765]; American Lebanese Syrian Associated Charities; Dutch Cancer Society, Amsterdam, Netherlands [UVA 2011-4938]; 7th Framework Program of the European Union, PanCareSurfUp [257505]; NCI/NIDDK [1R01CA113930]; NIDDK [1R01DK072124]; Stichting Kinderen Kankervrij, Netherlands; Tom Voute Foundation, Amsterdam, Netherlands FX SHA is supported by the National Institutes of Health (NCI; 2 K12 CA001727-14, 1 U10 CA098543). MMH is supported by the Cancer Center Support (CORE) grant CA 21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities. RLM is supported by the Dutch Cancer Society, Amsterdam, Netherlands (UVA 2011-4938). GL and RS are supported in part by the 7th Framework Program of the European Union, PanCareSurfUp (257505). JS is supported by NCI/NIDDK: 1R01CA113930, NIDDK: 1R01DK072124. ECvD is supported by Stichting Kinderen Kankervrij, Netherlands. HvdP is supported by the Tom Voute Foundation, Amsterdam, Netherlands. We thank Kevin Oeffinger and Jako Burgers for critically appraising the recommendations and the manuscript as external reviewers. We would like to thank the experts of the International Late Effects of Childhood Cancer Guideline Harmonization Group and members of the PanCareSurfUp Consortium for their participation in the international guideline harmonization process: Smita Bhatia, Wendy Landier, Edit Bardi, Eva Frey, Riccardo Haupt, Claudia Kuhni, Gisela Michel, Flora van Leeuwen, Cecile Ronckers, Berthe Aleman, Gregory Armstrong, Eric Chow, Richard Cohn, Junichiro Fujimoto, Satomi Funaki, Daniel Green, Tara Henderson, Lars Hjorth, David Hodgson, Hiroyuki Ishiguro, Shunichi Kato, Chikako Kiyotani, Miho Maeda, Michael Schaapveld, Jane Skeen, and Charles Sklar. NR 108 TC 43 Z9 43 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2015 VL 16 IS 3 BP E123 EP E136 PG 14 WC Oncology SC Oncology GA CC7WA UT WOS:000350577900026 PM 25752563 ER PT J AU DeAngelo, DJ Stevenson, KE Dahlberg, SE Silverman, LB Couban, S Supko, JG Amrein, PC Ballen, KK Seftel, MD Turner, AR Leber, B Howson-Jan, K Kelly, K Cohen, S Matthews, JH Savoie, L Wadleigh, M Sirulnik, LA Galinsky, I Neuberg, DS Sallan, SE Stone, RM AF DeAngelo, D. J. Stevenson, K. E. Dahlberg, S. E. Silverman, L. B. Couban, S. Supko, J. G. Amrein, P. C. Ballen, K. K. Seftel, M. D. Turner, A. R. Leber, B. Howson-Jan, K. Kelly, K. Cohen, S. Matthews, J. H. Savoie, L. Wadleigh, M. Sirulnik, L. A. Galinsky, I. Neuberg, D. S. Sallan, S. E. Stone, R. M. TI Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia SO LEUKEMIA LA English DT Article ID FARBER-CANCER-INSTITUTE; COLI L-ASPARAGINASE; YOUNG-ADULTS; INDUCTION FAILURE; REMISSION INDUCTION; CEREBROSPINAL-FLUID; GROUP-B; ADOLESCENTS; CHILDREN; PROTOCOLS AB On the basis of the data suggesting that adolescents and young adult patients with acute lymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric protocols, we assessed the feasibility of treating adult patients aged 18-50 years with ALL with the DFCI Pediatric ALL Consortium regimen utilizing a 30-week course of pharmacokinetically dose-adjusted E. call L-asparaginase during consolidation. Between 2002 and 2008,92 eligible patients aged 18-50 years were enrolled at 13 participating centers. Seventy-eight patients (85%) achieved a complete remission (CR) after 1 month of intensive induction therapy. With a median follow-up of 4.5 years, the 4-year disease-free survival (DFS) for the patients achieving a CR was 69% (95% confidence interval (CI) 56-78%) and the 4-year overall survival (OS) for all eligible patients was 67% (95% CI 56-76%). The 4-year DFS for the 64 patients who achieved a CR and were Philadelphia chromosome negative (Ph-) was 71% (95% CI 58-81%), and for all 74 Ph- patients the 4-year OS was 70% (95% CI 58-79%), We conclude that a pediatric-like treatment strategy for young adults with de novo ALL is feasible, associated with tolerable toxicity, and results in improved outcomes compared with historical regimens in young adult patients with ALL. C1 [DeAngelo, D. J.; Wadleigh, M.; Sirulnik, L. A.; Galinsky, I.; Stone, R. M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Stevenson, K. E.; Dahlberg, S. E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Silverman, L. B.; Sallan, S. E.] Boston Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Pediat Hematol Oncol, Boston, MA USA. [Couban, S.] Canada Clin Trials Grp, Natl Canc Inst, Kingston, ON, Canada. [Couban, S.] Dalhousie Univ, Halifax, NS, Canada. [Supko, J. G.; Amrein, P. C.; Ballen, K. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seftel, M. D.] Canc Care Manitoba, Winnipeg, MB, Canada. [Turner, A. R.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Leber, B.] Hamilton Hlth Sci Ctr, Hamilton, ON, Canada. [Howson-Jan, K.] London Hlth Serv, London, ON, Canada. [Kelly, K.] Columbia Univ, Med Ctr, New York, NY USA. [Cohen, S.] Hosp Maisonneuve Rosemont, Montreal, PQ, Canada. [Matthews, J. H.] Queens Univ, Kingston, ON, Canada. [Savoie, L.] Tom Baker Canc Clin, Calgary, AB, Canada. RP DeAngelo, DJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,D1 B30, Boston, MA 02215 USA. EM daniel_deangelo@dfci.harvard.edu FU NIH [PO1 CA068484] FX We thank Susan Buchanan, PA-C, Adriana Pcnicaud, PA-C and Kristina Hines for technical assistance. This study was supported in part by NIH Grant PO1 CA068484. Sigma Tau has partially funded the laboratory performing Asparaginasc enzyme level testing. NR 34 TC 35 Z9 36 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAR PY 2015 VL 29 IS 3 BP 526 EP 534 DI 10.1038/leu.2014.229 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CD0BE UT WOS:000350734300002 PM 25079173 ER PT J AU Niederwieser, C Kohlschmidt, J Volinia, S Whitman, SP Metzeler, KH Eisfeld, AK Maharry, K Yan, P Frankhouser, D Becker, H Schwind, S Carroll, AJ Nicolet, D Mendler, JH Curfman, JP Wu, YZ Baer, MR Powell, BL Kolitz, JE Moore, JO Carter, TH Bundschuh, R Larson, RA Stone, RM Mrozek, K Marcucci, G Bloomfield, CD AF Niederwieser, C. Kohlschmidt, J. Volinia, S. Whitman, S. P. Metzeler, K. H. Eisfeld, A-K Maharry, K. Yan, P. Frankhouser, D. Becker, H. Schwind, S. Carroll, A. J. Nicolet, D. Mendler, J. h Curfman, J. P. Wu, Y-Z Baer, M. R. Powell, B. L. Kolitz, J. E. Moore, J. O. Carter, T. H. Bundschuh, R. Larson, R. A. Stone, R. M. Mrozek, K. Marcucci, G. Bloomfield, C. D. TI Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia SO LEUKEMIA LA English DT Article ID INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; GROUP-B; MICRORNA-EXPRESSION; HEMATOLOGIC MALIGNANCIES; EUROPEAN LEUKEMIANET; CLINICAL IMPACT; POOR-PROGNOSIS; DISTINCT GENE AB DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (>= 60 years) adults with primary, cytogenetically normal acute myeloid leukemia (CN-AML). Patients were dichotomized into high versus low expressers using median cut. Outcomes were assessed in the context of known CN-AML prognosticators. Gene and microRNA expression, and DNA methylation profiles were analyzed using microarrays and MethylCap-sequencing, respectively. High DNMT3B expressers had fewer complete remissions (CR; P = 0.002) and shorter disease-free (DFS; P = 0.02) and overall (OS; P < 0.001) survival. In multivariable analyses, high DNMT3B expression remained an independent predictor of lower CR rates (P = 0.04) and shorter DFS (P = 0.04) and OS (P = 0.001). High DNMT3B expression associated with a gene expression profile comprising 363 genes involved in differentiation, proliferation and survival pathways, but with only four differentially expressed microRNAs (miR-133b, miR-148a, miR-122, miR-409-3p) and no differential DNA methylation regions. We conclude that high DNMT3B expression independently associates with adverse outcome in older CN-AML patients. Gene expression analyses suggest that DNMT3B is involved in the modulation of several genes, although the regulatory mechanisms remain to be investigated to devise therapeutic approaches specific for these patients. C1 [Niederwieser, C.; Kohlschmidt, J.; Volinia, S.; Whitman, S. P.; Metzeler, K. H.; Eisfeld, A-K; Maharry, K.; Yan, P.; Frankhouser, D.; Becker, H.; Schwind, S.; Nicolet, D.; Mendler, J. h; Curfman, J. P.; Wu, Y-Z; Mrozek, K.; Marcucci, G.; Bloomfield, C. D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Kohlschmidt, J.; Maharry, K.; Nicolet, D.] Mayo Clin, Alliance Clin Trials Oncol, Stat & Data Ctr, Rochester, MN USA. [Carroll, A. J.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Baer, M. R.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Baer, M. R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Powell, B. L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Kolitz, J. E.] Hofstra North Shore Long Isl Jewish Sch Med, Monter Canc Ctr, Lake Success, NY USA. [Moore, J. O.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Carter, T. H.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Bundschuh, R.] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA. [Bundschuh, R.] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA. [Larson, R. A.] Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA. [Stone, R. M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Mrozek, K (reprint author), Ohio State Univ, Ctr Comprehens Canc, 1232 A James Canc Hosp,300 West Tenth Ave, Columbus, OH 43210 USA. EM krzysztof.mrozek@osumc.edu; guido.marcucci@osumc.edu; clara.bloomfield@osumc.edu RI Bundschuh, Ralf/B-9623-2008; Mrozek, Krzysztof/A-3142-2008; Metzeler, Klaus/C-2118-2009; Yan, Pearlly/E-4339-2011; OI Volinia, Stefano/0000-0003-0910-3893; Bundschuh, Ralf/0000-0002-6699-8614; Metzeler, Klaus/0000-0003-3920-7490; Yan, Pearlly/0000-0003-1965-4920; Mendler, Jason/0000-0001-5605-5324; Larson, Richard/0000-0001-9168-3203 FU National Cancer Institute [CA101140, CA114725, CA140158, CA31946, CA33601, CA16058, CA77658, CA129657]; Coleman Leukemia Research Foundation; Pelotonia Fellowship Program; Conquer Cancer Foundation; Deutsche Krebshilfe-Dr Mildred Scheel Cancer Foundation FX The Cancer and Leukemia Group B institutions, and their principal investigators participating in this study are provided in the Supplementary Information. We thank Donna Bucci and the CALGB/Alliance Leukemia Tissue Bank at The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA for sample processing and storage services; Lisa J. Sterling and Chris Finks for data management; and The Ohio State University Comprehensive Cancer Center's Nucleic Acid and Microarray Shared Resources for technical support. This work was supported in part by the National Cancer Institute (grants CA101140, CA114725, CA140158, CA31946, CA33601, CA16058, CA77658 and CA129657), the Coleman Leukemia Research Foundation, the Pelotonia Fellowship Program (A-KE), the Conquer Cancer Foundation (JHM) and the Deutsche Krebshilfe-Dr Mildred Scheel Cancer Foundation (HB). NR 59 TC 21 Z9 22 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAR PY 2015 VL 29 IS 3 BP 567 EP 575 DI 10.1038/leu.2014.267 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CD0BE UT WOS:000350734300006 PM 25204569 ER PT J AU Jagannathan, S Vad, N Vallabhapurapu, S Vallabhapurapu, S Anderson, KC Driscoll, JJ AF Jagannathan, S. Vad, N. Vallabhapurapu, S. Vallabhapurapu, S. Anderson, K. C. Driscoll, J. J. TI MiR-29b replacement inhibits proteasomes and disrupts aggresome plus autophagosome formation to enhance the antimyeloma benefit of bortezomib SO LEUKEMIA LA English DT Article ID REFRACTORY MULTIPLE-MYELOMA; MICRORNA EXPRESSION; ANTITUMOR-ACTIVITY; TUMOR-SUPPRESSOR; ACTIVATOR PA200; IN-VIVO; CELLS; SYSTEM; RESISTANCE; DEXAMETHASONE AB Evading apoptosis is a cancer hallmark that remains a serious obstacle in current treatment approaches. Although proteasome inhibitors (PIs) have transformed management of multiple myeloma (MM), drug resistance emerges through induction of the aggresome+autophagy pathway as a compensatory protein clearance mechanism. Genome-wide profiling identified microRNAs (miRs) differentially expressed in bortezomib-resistant myeloma cells compared with drug-naive cells. The effect of individual miRs on proteasomal degradation of short-lived fluorescent reporter proteins was then determined in live cells. MiR-29b was significantly reduced in bortezomib-resistant cells as well as in cells resistant to second-generation PIs carfilzomib and ixazomib. Luciferase reporter assays demonstrated that miR-29b targeted PSME4 that encodes the proteasome activator PA200. Synthetically engineered miR-29b replacements impaired the growth of myeloma cells, patient tumor cells and xenotransplants. MiR-29b replacements also decreased PA200 association with proteasomes, reduced the proteasome's peptidase activity and inhibited ornithine decarboxylase turnover, a proteasome substrate degraded through ubiquitin-independent mechanisms. Immunofluorescence studies revealed that miR-29b replacements enhanced the bortezomib-induced accumulation of ubiquitinated proteins but did not reveal aggresome or autophagosome formation. Taken together, our study identifies miR-29b replacements as the first-in-class miR-based PIs that also disrupt the autophagy pathway and highlight their potential to synergistically enhance the antimyeloma effect of bortezomib. C1 [Jagannathan, S.; Vad, N.; Driscoll, J. J.] Univ Cincinnati, Coll Med, Vontz Ctr Mol Studies, Cincinnati, OH 45267 USA. [Jagannathan, S.; Vad, N.; Driscoll, J. J.] Univ Cincinnati, Coll Med, Vontz Ctr Mol Studies, Div Hematol & Oncol, Cincinnati, OH 45267 USA. [Vallabhapurapu, S.; Vallabhapurapu, S.; Driscoll, J. J.] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH 45267 USA. [Anderson, K. C.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. [Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. RP Driscoll, JJ (reprint author), Univ Cincinnati, Coll Med, Vontz Ctr Mol Studies, 3125 Eden Ave, Cincinnati, OH 45267 USA. EM driscojs@uc.edu FU NCI NIH HHS [P01 CA155258, P50 CA100707] NR 51 TC 15 Z9 17 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAR PY 2015 VL 29 IS 3 BP 727 EP 738 DI 10.1038/leu.2014.279 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA CD0BE UT WOS:000350734300023 PM 25234165 ER PT J AU Unkelbach, J Bortfeld, T Craft, D Alber, M Bangert, M Bokrantz, R Chen, D Li, RJ Xing, L Men, CH Nill, S Papp, D Romeijn, E Salari, E AF Unkelbach, Jan Bortfeld, Thomas Craft, David Alber, Markus Bangert, Mark Bokrantz, Rasmus Chen, Danny Li, Ruijiang Xing, Lei Men, Chunhua Nill, Simeon Papp, David Romeijn, Edwin Salari, Ehsan TI Optimization approaches to volumetric modulated arc therapy planning SO MEDICAL PHYSICS LA English DT Review DE radiotherapy; treatment plan optimization; VMAT ID BEAM ANGLE OPTIMIZATION; RADIATION-THERAPY; SHOOT IMRT; VMAT; RADIOTHERAPY; GENERATION; ALGORITHM; TOMOTHERAPY; DELIVERY; EFFICIENCY AB Volumetric modulated arc therapy (VMAT) has found widespread clinical application in recent years. A large number of treatment planning studies have evaluated the potential for VMAT for different disease sites based on the currently available commercial implementations of VMAT planning. In contrast, literature on the underlying mathematical optimization methods used in treatment planning is scarce. VMAT planning represents a challenging large scale optimization problem. In contrast to fluence map optimization in intensity-modulated radiotherapy planning for static beams, VMAT planning represents a nonconvex optimization problem. In this paper, the authors review the state-of-the-art in VMAT planning from an algorithmic perspective. Different approaches to VMAT optimization, including arc sequencing methods, extensions of direct aperture optimization, and direct optimization of leaf trajectories are reviewed. Their advantages and limitations are outlined and recommendations for improvements are discussed. (C) 2015 American Association of Physicists in Medicine. C1 [Unkelbach, Jan; Bortfeld, Thomas; Craft, David] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Unkelbach, Jan; Bortfeld, Thomas; Craft, David] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Alber, Markus] Aarhus Univ Hosp, Dept Med Phys, DK-8000 Aarhus C, Denmark. [Alber, Markus] Aarhus Univ Hosp, Dept Radiat Oncol, DK-8000 Aarhus C, Denmark. [Bangert, Mark] German Canc Res Ctr, Dept Med Phys Radiat Oncol, D-69120 Heidelberg, Germany. [Bokrantz, Rasmus] RaySearch Labs, SE-11134 Stockholm, Sweden. [Chen, Danny] Univ Notre Dame, Dept Comp Sci & Engn, Notre Dame, IN 46556 USA. [Li, Ruijiang; Xing, Lei] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA. [Men, Chunhua] Elekta, Dept Res, Maryland Hts, MO 63043 USA. [Nill, Simeon] Inst Canc Res, Joint Dept Phys, Sutton SM2 5NG, Surrey, England. [Nill, Simeon] Royal Marsden NHS Fdn Trust, Sutton SM2 5NG, Surrey, England. [Papp, David] N Carolina State Univ, Dept Math, Raleigh, NC 27695 USA. [Romeijn, Edwin] Georgia Inst Technol, H Milton Stewart Sch Ind & Syst Engn, Atlanta, GA 30332 USA. [Salari, Ehsan] Wichita State Univ, Dept Ind & Mfg Engn, Wichita, KS 67260 USA. RP Unkelbach, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM junkelbach@mgh.harvard.edu FU NCI NIH HHS [R01 CA176553] NR 46 TC 4 Z9 4 U1 0 U2 11 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 MAR PY 2015 VL 42 IS 3 BP 1367 EP 1377 DI 10.1118/1.4908224 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CC9BC UT WOS:000350661500022 PM 25735291 ER PT J AU Daifalla, N Cayabyab, MJ Xie, E Kim, HB Tzipori, S Stashenko, P Duncan, M Campos-Neto, A AF Daifalla, Nada Cayabyab, Mark J. Xie, Emily Kim, Hyeun Bum Tzipori, Saul Stashenko, Philip Duncan, Margaret Campos-Neto, Antonio TI Commensal Streptococcus mitis is a unique vector for oral mucosal vaccination SO MICROBES AND INFECTION LA English DT Article DE Streptococcus mitis; Ag85b; Vaccine vector; Oral immunization; Mucosal vaccine; Gnotobiotic piglets ID VACCINES; LIVE; IMMUNITY; ANTIGEN; CAVITY; IMMUNIZATION; PROTEIN; UPDATE; STRAIN; TRIAL AB The development of vaccine approaches that induce mucosal and systemic immune responses is critical for the effective prevention of several infections. Here, we report on the use of the abundant human oral commensal bacterium Streptococcus mitis as a delivery vehicle for mucosal immunization. Using homologous recombination we generated a stable rS. mitis expressing a Mycobacterium tuberculosis protein (Ag85b). Oral administration of rS. mitis in gnotobiotic piglets resulted in efficient oral colonization and production of oral and systemic anti-Ag85b specific IgA and IgG antibodies. These results support that the commensal S. mitis is potentially a useful vector for mucosal vaccination. (C) 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. C1 [Daifalla, Nada; Cayabyab, Mark J.; Xie, Emily; Stashenko, Philip; Duncan, Margaret; Campos-Neto, Antonio] Forsyth Inst, Cambridge, MA 02142 USA. [Kim, Hyeun Bum; Tzipori, Saul] Cummings Sch Vet Med Tufts, Grafton, MA USA. [Kim, Hyeun Bum] Dankook Univ, Dept Anim Resources Sci, Cheonan, South Africa. RP Campos-Neto, A (reprint author), Forsyth Inst, Cambridge, MA 02142 USA. EM acampos@forsyth.org RI Daifalla, Nada/E-6005-2017 FU NIH [R03 DE022525, R01 DE015931, R01 AI076425] FX This study was supported in part by NIH grants R03 DE022525 (M.C.), R01 DE015931 (M.D.), and R01 AI076425 (A.C-N.). NR 27 TC 3 Z9 3 U1 0 U2 4 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 MAR PY 2015 VL 17 IS 3 BP 237 EP 242 DI 10.1016/j.micinf.2014.11.002 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CD5CZ UT WOS:000351106800008 PM 25522856 ER PT J AU Kressin, NR Groeneveld, PW AF Kressin, Nancy R. Groeneveld, Peter W. TI Race/Ethnicity and Overuse of Care: A Systematic Review SO MILBANK QUARTERLY LA English DT Review DE guideline adherence; inappropriate utilization; inappropriate test ID RESPIRATORY-TRACT INFECTIONS; POPULATION-BASED-ANALYSIS; LOW-BACK-PAIN; UNITED-STATES; RACIAL-DIFFERENCES; CARDIAC REVASCULARIZATION; CAROTID-ENDARTERECTOMY; EMERGENCY-DEPARTMENTS; ANTIBIOTIC-TREATMENT; REGIONAL-VARIATIONS AB Policy Points: Racial/ethnic differences in the overuse of care (specifically, unneeded care that does not improve patients' outcomes) have received little scholarly attention. Our systematic review of the literature (59 studies) found that the overuse of care is not invariably associated with race/ethnicity, but when it was, a substantial proportion of studies found greater overuse of care among white patients. The absence of established subject terms in PubMed for the overuse of care or inappropriate care impedes the ability of researchers or policymakers to synthesize prior scientific or policy efforts. ContextThe literature on disparities in health care has examined the contrast between white patients receiving needed care, compared with racial/ethnic minority patients not receiving needed care. Racial/ethnic differences in the overuse of care, that is, unneeded care that does not improve patients' outcomes, have received less attention. We systematically reviewed the literature regarding race/ethnicity and the overuse of care. MethodsWe searched the Medline database for US studies that included at least 2 racial/ethnic groups and that examined the association between race/ethnicity and the overuse of procedures, diagnostic (care) or therapeutic care. In a recent review, we identified studies of overuse by race/ethnicity, and we also examined reference lists of retrieved articles. We then abstracted and evaluated this information, including the population studied, data source, sample size and assembly, type of care, guideline or appropriateness standard, controls for clinical confounding and financing of care, and findings. FindingsWe identified 59 unique studies, of which 11 had a low risk of methodological bias. Studies with multiple outcomes were counted more than once; collectively they assessed 74 different outcomes. Thirty-two studies, 6 with low risks of bias (LRoB), provided evidence that whites received more inappropriate or nonrecommended care than racial/ethnic minorities did. Nine studies (2 LRoB) found evidence of more overuse of care by minorities than by whites. Thirty-three studies (6 LRoB) found no relationship between race/ethnicity and overuse. ConclusionsAlthough the overuse of care is not invariably associated with race/ethnicity, when it was, a substantial proportion of studies found greater overuse of care among white patients. Clinicians and researchers should try to understand how and why race/ethnicity might be associated with overuse and to intervene to reduce it. C1 [Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Med, Boston, MA 02215 USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Hlth Care Dispar Res Program, Sect Gen Internal Med,Dept Med, Boston, MA 02215 USA. [Groeneveld, Peter W.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Groeneveld, Peter W.] Univ Penn, Perelman Sch Med, Med, Philadelphia, PA 19104 USA. RP Kressin, NR (reprint author), Crosstown Ctr, Gen Internal Med Sect, 801 Massachusetts Ave,2nd Fl,Rm 2090, Boston, MA 02118 USA. EM nkressin@bu.edu FU Veterans Affairs Health Services Research and Development Service [RCS-02-066-1]; NIH/NHLBI [1U01HL105342-01] FX Nancy Kressin was supported by a Senior Research Career Scientist award from the Veterans Affairs Health Services Research and Development Service (RCS-02-066-1). This research also was supported by a grant: NIH/NHLBI (1U01HL105342-01, N. Kressin, PI). The sponsors 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. NR 96 TC 4 Z9 4 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-378X EI 1468-0009 J9 MILBANK Q JI Milbank Q. PD MAR PY 2015 VL 93 IS 1 BP 112 EP 138 DI 10.1111/1468-0009.12107 PG 27 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CD0HZ UT WOS:000350752800012 PM 25752352 ER PT J AU Shi, M Movius, J Dator, R Aro, P Zhao, YC Pan, C Lin, XM Bammler, TK Stewart, T Zabetian, CP Peskind, ER Hu, SC Quinn, JF Galasko, DR Zhang, J AF Shi, Min Movius, James Dator, Romel Aro, Patrick Zhao, Yanchun Pan, Catherine Lin, Xiangmin Bammler, Theo K. Stewart, Tessandra Zabetian, Cyrus P. Peskind, Elaine R. Hu, Shu-Ching Quinn, Joseph F. Galasko, Douglas R. Zhang, Jing TI Cerebrospinal Fluid Peptides as Potential Parkinson Disease Biomarkers: A Staged Pipeline for Discovery and Validation SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID PRECURSOR-LIKE PROTEIN-1; NEURODEGENERATIVE DISEASES; MATRIX METALLOPROTEINASES; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; CLINICAL-FEATURES; SUBSTANTIA-NIGRA; TISSUE INHIBITOR; AMYLOID-BETA; IDENTIFICATION AB Finding robust biomarkers for Parkinson disease (PD) is currently hampered by inherent technical limitations associated with imaging or antibody-based protein assays. To circumvent the challenges, we adapted a staged pipeline, starting from our previous proteomic profiling followed by high-throughput targeted mass spectrometry (MS), to identify peptides in human cerebrospinal fluid (CSF) for PD diagnosis and disease severity correlation. In this multicenter study consisting of training and validation sets, a total of 178 subjects were randomly selected from a retrospective cohort, matching age and sex between PD patients, healthy controls, and neurological controls with Alzheimer disease (AD). From similar to 14,000 unique peptides displaying differences between PD and healthy control in proteomic investigations, 126 peptides were selected based on relevance and observability in CSF using bioinformatic analysis and MS screening, and then quantified by highly accurate and sensitive selected reaction monitoring (SRM) in the CSF of 30 PD patients versus 30 healthy controls (training set), followed by diagnostic (receiver operating characteristics) and disease severity correlation analyses. The most promising candidates were further tested in an independent cohort of 40 PD patients, 38 AD patients, and 40 healthy controls (validation set). A panel of five peptides (derived from SPP1, LRP1, CSF1R, EPHA4, and TIMP1) was identified to provide an area under curve (AUC) of 0.873 (sensitivity = 76.7%, specificity = 80.0%) for PD versus healthy controls in the training set. The performance was essentially confirmed in the validation set (AUC = 0.853, sensitivity = 82.5%, specificity = 82.5%). Additionally, this panel could also differentiate the PD and AD groups (AUC = 0.990, sensitivity = 95.0%, specificity = 97.4%). Furthermore, a combination of two peptides belonging to proteins TIMP1 and APLP1 significantly correlated with disease severity as determined by the Unified Parkinson's Disease Rating Scale motor scores in both the training (r = 0.381, p = 0.038) j and the validation (r = 0.339, p = 0.032) sets. The novel panel of CSF peptides, if validated in independent cohorts, could be used to assist in clinical diagnosis of PD and has the potential to help monitoring or predicting disease progression. C1 [Shi, Min; Movius, James; Dator, Romel; Aro, Patrick; Zhao, Yanchun; Pan, Catherine; Lin, Xiangmin; Stewart, Tessandra; Zhang, Jing] Univ Washington, Dept Pathol, Sch Med, Seattle, WA 98104 USA. [Lin, Xiangmin] Fujian Agr & Forestry Univ, Sch Life Sci, Fuzhou 350002, Fujian, Peoples R China. [Bammler, Theo K.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Zabetian, Cyrus P.; Hu, Shu-Ching] Vet Affairs Puget Sound Hlth Care Syst, Geriatr & Parkinsons Dis Res Ctr, Seattle, WA 98108 USA. [Zabetian, Cyrus P.; Hu, Shu-Ching] Vet Affairs Puget Sound Hlth Care Syst, Geriatr & Parkinsons Educ Ctr, Seattle, WA 98108 USA. [Zabetian, Cyrus P.; Hu, Shu-Ching] Vet Affairs Puget Sound Hlth Care Syst, Geriatr & Parkinsons Clin Ctr, Seattle, WA 98108 USA. [Zabetian, Cyrus P.; Hu, Shu-Ching] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. [Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Peskind, Elaine R.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Zhang, J (reprint author), Univ Washington, Dept Pathol, Sch Med, HMC Box 359635,325 9th Ave, Seattle, WA 98104 USA. EM zhangj@u.washington.edu RI Shi, Min/G-6165-2012; OI Shi, Min/0000-0002-6901-2558; , xiangmin/0000-0001-9128-689X; Lin, Xiangmin/0000-0003-2216-0198 FU National Institutes of Health (NIH) [U01 NS082137, P42 ES004696-5897, P30 ES007033-6364, R01 AG033398, R01 ES016873, R01 ES019277, R01 NS057567, P50 NS062684-6221, R01 NS065070, P50 AG005131]; NIH [P50 AG003156-30]; National Institute of Neurological Disorders and Stroke/NIH [R21 NS085425]; University of Washington's Proteomics Resource [UWPR95794]; National Institute Of Environmental Health Sciences of the NIH [P30 ES007033]; National Natural Science Foundation of China (NSFC) [31200105, 31470238] FX This study was supported by generous grants from the National Institutes of Health (NIH) (U01 NS082137, P42 ES004696-5897, P30 ES007033-6364, R01 AG033398, R01 ES016873, R01 ES019277, R01 NS057567, and P50 NS062684-6221 to JZ, R01 NS065070 to CPZ, and P50 AG005131 to DRG), and partially by a pilot study award from the NIH-sponsored ADRC at the UW (P50 AG003156-30) and a National Institute of Neurological Disorders and Stroke/NIH award R21 NS085425 to MS. It was also supported in part by the University of Washington's Proteomics Resource (UWPR95794), the National Institute Of Environmental Health Sciences of the NIH under Award Number P30 ES007033, and the National Natural Science Foundation of China (NSFC) projects (31200105 and 31470238). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and other sponsors. NR 58 TC 11 Z9 11 U1 1 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAR PY 2015 VL 14 IS 3 BP 544 EP 555 DI 10.1074/mcp.M114.040576 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CC9EP UT WOS:000350671300009 PM 25556233 ER PT J AU Zhang, X Miller, KW AF Zhang, Xi Miller, Keith W. TI Dodecyl Maltopyranoside Enabled Purification of Active Human GABA Type A Receptors for Deep and Direct Proteomic Sequencing SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID CHILDHOOD ABSENCE EPILEPSY; MASS-SPECTROMETRIC ANALYSIS; PROTEIN-COUPLED RECEPTOR; CYTOCHROME-C-OXIDASE; NICOTINIC ACETYLCHOLINE-RECEPTOR; X-RAY-STRUCTURE; MEMBRANE-PROTEINS; CRYSTAL-STRUCTURE; PHOSPHORYLATION SITES; SHOTGUN PROTEOMICS AB The challenge in high-quality membrane proteomics is all about sample preparation prior to HPLC, and the cell-to-protein step poses a long-standing bottleneck. Traditional protein extraction methods apply ionic or poly-disperse detergents, harsh denaturation, and repeated protein/peptide precipitation/resolubilization afterward, but suffer low yield, low reproducibility, and low sequence coverage. Contrary to attempts to subdue, we resolved this challenge by providing proteins nature-and-activity-promoting conditions throughout preparation. Using 285-kDa hetero-pentameric human GABA type A receptor overexpressed in HEK293 as a model, we describe a n-dodecyl-beta-D-maltopyranoside/cholesteryl hemisuccinate (DDM/CHS)-based affinity purification method, that produced active receptors, supported protease activity, and allowed high performance with both in-gel and direct gel-free proteomic analyses-without detergent removal. Unlike conventional belief that detergents must be removed before HPLC MS, the high-purity low-dose nonionic detergent DDM did not interfere with peptides, and obviated removal or desalting. Sonication or dropwise addition of detergent robustly solubilized over 90% of membrane pellets. The purification conditions were comparable to those applied in successful crystallizations of most membrane proteins. These results enabled streamlined proteomics of human synaptic membrane proteins, and more importantly, allowed directly coupling proteomics with crystallography to characterize both static and dynamic structures of membrane proteins in crystallization pipelines. C1 [Zhang, Xi; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Zhang, Xi; Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Zhang, X (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 32 Fruit St, Boston, MA 02114 USA. EM xi.zhang.edu@gmail.com OI Zhang, Xi/0000-0003-2755-7901 FU National Institute of General Medical Sciences [GM 58448]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX This work was supported in part by the National Institute of General Medical Sciences (GM 58448, K.W.M.) and by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital (K.W.M.). NR 70 TC 4 Z9 4 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAR PY 2015 VL 14 IS 3 BP 724 EP 738 DI 10.1074/mcp.M114.042556 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CC9EP UT WOS:000350671300023 PM 25473089 ER PT J AU Wong, SCK Sasportas, LS Richardson, K Gordon, BR Jayatunga, MKP Shalizi, A Pfister, SX Stanzl, EG Chui, C Mathur, M Thomsen, SK Shetty, C Pliuskys, L Mehra, A Bahar, H Godec, J Jong, S Perez, DA AF Wong, Sybil C. K. Sasportas, Laura S. Richardson, Katie Gordon, Brian R. Jayatunga, Madura K. P. Shalizi, Aryaman Pfister, Sophia X. Stanzl, Erika G. Chui, Cecilia Mathur, Melina Thomsen, Soren K. Shetty, Charvi Pliuskys, Laurynas Mehra, Akhil Bahar, Hila Godec, Jernej Jong, Simcha Perez, Daniel A. TI Keys to the kingdom SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 [Wong, Sybil C. K.; Perez, Daniel A.] Oxbridge Biotech Roundtable, London, England. [Sasportas, Laura S.; Mathur, Melina] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Sasportas, Laura S.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Richardson, Katie] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England. [Gordon, Brian R.] BRGordon Partners, San Francisco, CA USA. [Jayatunga, Madura K. P.] Univ Oxford, Dept Organ Chem, Chem Res Lab, Oxford, England. [Shalizi, Aryaman] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Pfister, Sophia X.] CRUK MRC Oxford Inst Radiat Oncol, Oxford, England. [Stanzl, Erika G.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA. [Chui, Cecilia] Univ Oxford, Oxford, England. [Thomsen, Soren K.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Shetty, Charvi] KNOX Med Diagnost Inc, San Francisco, CA USA. [Pliuskys, Laurynas] Univ Oxford, Doctoral Training Ctr, Oxford, England. [Mehra, Akhil] Univ Calif San Francisco, Dept Anthropol Hist & Social Med, San Francisco, CA 94143 USA. [Bahar, Hila] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bahar, Hila] Harvard Univ, Sch Med, Boston, MA USA. [Godec, Jernej] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Godec, Jernej] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA USA. [Jong, Simcha] UCL, Dept Management Sci & Innovat, London, England. [Perez, Daniel A.] Univ Oxford, Dept Biochem, Glycobiol Inst, Oxford OX1 3QU, England. RP Wong, SCK (reprint author), Oxbridge Biotech Roundtable, London, England. EM dan@oxbridgebiotech.com RI Pfister, Stefan/F-6860-2013; OI Pfister, Stefan/0000-0002-5447-5322; Wong, Sybil/0000-0001-5238-2109; Jong, Simcha/0000-0002-3281-5381 NR 6 TC 1 Z9 1 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2015 VL 33 IS 3 BP 232 EP 236 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CD0ME UT WOS:000350766900013 PM 25748908 ER PT J AU Ziller, MJ Hansen, KD Meissner, A Aryee, MJ AF Ziller, Michael J. Hansen, Kasper D. Meissner, Alexander Aryee, Martin J. TI Coverage recommendations for methylation analysis by whole-genome bisulfite sequencing SO NATURE METHODS LA English DT Article ID MAMMALIAN DEVELOPMENT; BIOINFORMATICS; BIOLOGY AB Whole-genome bisulfite sequencing (WGBSBS) allows genome-wide DNA methylation profiling, but the associated high sequencing costs continue to limit its widespread application. We used several high-coverage reference data sets to experimentally determine minimal sequencing requirements. We present data-derived recommendations for minimum sequencing depth for WGBSBS libraries, highlight what is gained with increasing coverage and discuss the trade-off between sequencing depth and number of assayed replicates. C1 [Ziller, Michael J.; Meissner, Alexander; Aryee, Martin J.] Broad Inst & Harvard, Cambridge, MA 02139 USA. [Ziller, Michael J.; Meissner, Alexander] Harvard Stem Cell Inst, Cambridge, MA USA. [Ziller, Michael J.; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hansen, Kasper D.] Johns Hopkins Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Hansen, Kasper D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Aryee, Martin J.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Aryee, Martin J.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Aryee, Martin J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Aryee, MJ (reprint author), Broad Inst & Harvard, Cambridge, MA 02139 USA. EM alex@broadinstitute.org; aryee.martin@mgh.harvard.edu OI Aryee, Martin/0000-0002-6848-1344 FU NIH Common Fund [U01ES017155]; NIGMS [P01GM099117]; New York Stem Cell Foundation FX This work was supported by the NIH Common Fund (U01ES017155), NIGMS (P01GM099117) and the New York Stem Cell Foundation. A.M. receives support as a New York Stem Cell Foundation Robertson Investigator. NR 15 TC 26 Z9 27 U1 4 U2 25 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 MAR PY 2015 VL 12 IS 3 BP 230 EP + DI 10.1038/NMETH.3152 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CC9EH UT WOS:000350670300023 PM 25362363 ER PT J AU Neal, JW Gainor, JF Shaw, AT AF Neal, Joel W. Gainor, Justin F. Shaw, Alice T. TI Developing biomarker-specific end points in lung cancer clinical trials SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; CIRCULATING TUMOR-CELLS; METASTATIC BREAST-CANCER; GROWTH-FACTOR RECEPTOR; PLATINUM-BASED CHEMOTHERAPY; PROTEIN-SYNTHESIS RATE; ADVANCED SOLID TUMORS; PHASE-III TRIAL; PROSTATE-CANCER; BRAIN-TUMORS AB In cancer-drug development, a number of different end points have been used to establish efficacy and support regulatory approval, such as overall survival, progression-free survival (PFS), and radiographic response rate. However, these traditional end points have important limitations. For example, in lung cancer clinical trials, evaluating overall survival end points is a protracted process and these end points are most reliable when crossover to the investigational therapy is not permitted. Furthermore, although radiographic surrogate end points, such as PFS and response rate, generally correlate with clinical benefit in the setting of cytotoxic chemotherapy and molecular targeted therapies, novel immunotherapies might have atypical response kinetics, which confounds radiographic interpretation. In this Review, we discuss the need to develop alternative or surrogate end points for lung cancer clinical trials, and focus on several new biomarkers that could serve as surrogate end points, including functional imaging biomarkers, circulating factors (tumour proteins, DNA, and cells), and pharmacodynamic tumour markers. By enabling the size, duration, and complexity of cancer trials to be reduced, biomarker end points hold the promise to accelerate drug development and improve patient outcomes. C1 [Neal, Joel W.] Stanford Univ, Stanford Canc Inst, Div Oncol, Dept Med, Stanford, CA 94305 USA. [Neal, Joel W.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Gainor, Justin F.; Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, 32 Fruit St, Boston, MA 02114 USA. EM ashaw1@mgh.harvard.edu FU NIH National Cancer Institute [C06CA059267, R01CA164273] FX We thank Dr Phil Lavori for helpful discussions surrounding statistical implications of biomarker-driven clinical trials. The work of J.F.G. is funded in part by the NIH National Cancer Institute (Grant: C06CA059267). The work of A.T.S. is funded in part by the NIH National Cancer Institute (Grant: R01CA164273). NR 126 TC 9 Z9 9 U1 1 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAR PY 2015 VL 12 IS 3 BP 135 EP 146 DI 10.1038/nrclinonc.2014.222 PG 12 WC Oncology SC Oncology GA CC9FG UT WOS:000350673000006 PM 25533947 ER PT J AU Yoder, KK Territo, PR Hutchins, GD Hannestad, J Morris, ED Gallezot, JD Normandin, MD Cosgrove, KP AF Yoder, Karmen K. Territo, Paul R. Hutchins, Gary D. Hannestad, Jonas Morris, Evan D. Gallezot, Jean-Dominique Normandin, Marc D. Cosgrove, Kelly P. TI Comparison of standardized uptake values with volume of distribution for quantitation of [C-11]PBR28 brain uptake SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE PET; PBR28; TSPO; SUV; Validity; Inflammation ID PROTEIN 18 KDA; POSITRON-EMISSION-TOMOGRAPHY; TRANSLOCATOR PROTEIN; ALZHEIMERS-DISEASE; IN-VIVO; BENZODIAZEPINE-RECEPTOR; RADIOLIGAND BINDING; INTERFERON-GAMMA; PET; INFLAMMATION AB Introduction: [C-11]PBR28 is a high-affinity ligand for the Translocator Protein 18 kDa (TSPO), which is considered to be a marker for microglial activation. Volume of distribution (V-T) estimated with an arterial plasma input function-is the gold standard for quantitation of [C-11]PBR28 binding. However, arterial sampling is impractical at many PET sites for multiple reasons. Reference region modeling approaches are not ideal for TSPO tracers, as the existence of a true reference region cannot be assumed. Given that it would be desirable to have a non-invasive index of [C-11]PBR28 binding, we elected to study the utility of the semi-quantitative metric, standardized uptake value (SUV) for use in brain [C-11]PBR PET studies. The primary goal of this study was to determine the relationship between SUV and V-T. Methods: We performed a retrospective analysis of data from sixteen [C-11]PBR28 PET scans acquired in baboons at baseline and at multiple time points after IV injection of lipopolysaccharide, an endotoxin that transiently induces neuroinflammation. For each scan, data from 14 brain regions of interest were studied. V-T was estimated with the Logan plot, using metabolite-corrected input functions. SUV was calculated with data from 30 to 60 minutes after [C-11]PBR28 injection. Results: Within individual PET studies, SUV tended to correlate well with V-T. Across studies, the relationship between SUV and V-T was variable. Conclusions: From study to study, there was variability in the degree of correlation between [C-11]PBR28 V-T and SUV. There are multiple physiological factors that may contribute to this variance. Advances in Knowledge: As currently applied, the non-invasive measurement of SUV does not appear to be a reliable outcome variable for [C-11]PBR28. Additional work is needed to discover the source of the discrepancy in SUV between [C-11]PBR28 scans. (C) 2014 Elsevier Inc. All rights reserved. C1 [Yoder, Karmen K.; Territo, Paul R.; Hutchins, Gary D.] Indiana Univ Sch Med, Radiol & Imaging Sci, Indianapolis, IN 46202 USA. [Yoder, Karmen K.; Hutchins, Gary D.] Indiana Univ Sch Med, Ctr Neuroimaging, Indianapolis, IN 46202 USA. [Yoder, Karmen K.] Indiana Univ Sch Med, Stark Neurosci Res Inst, Indianapolis, IN 46202 USA. [Hannestad, Jonas; Morris, Evan D.; Gallezot, Jean-Dominique; Cosgrove, Kelly P.] Yale Univ, Sch Med, Yale PET Ctr, New Haven, CT USA. [Normandin, Marc D.] Harvard Univ, Sch Med, Dept Radiol, Ctr Adv Med Imaging Sci,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Yoder, KK (reprint author), Indiana Univ Sch Med, Radiol & Imaging Sci, 950 W Walnut St R2,E124, Indianapolis, IN 46202 USA. EM kkyoder@iupui.edu RI Normandin, Marc/C-6728-2015 OI Normandin, Marc/0000-0003-1645-523X FU Department of the Army [W81XWH-08-2-0701]; Society for Nuclear Medicine; NIH [K12DA00167, K01DA020651] FX The authors would like to thank John West for computational support. The Department of the Army (W81XWH-08-2-0701, JH), the Society for Nuclear Medicine (Molecular Imaging Research Grant for Junior Medical Faculty, JH), and NIH (K12DA00167, JH; K01DA020651, KPC) provided funding and/or salary support. The U.S. Army Medical Research Acquisition Activity, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. The information does not necessarily reflect the position or the policy of the government, and no official endorsement should be inferred. NR 23 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 0969-8051 EI 1872-9614 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAR PY 2015 VL 42 IS 3 BP 305 EP 308 DI 10.1016/j.nucmedbio.2014.11.003 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD0RS UT WOS:000350782200015 PM 25487553 ER PT J AU Ratcliffe, D Sogg, S Friedman, KE AF Ratcliffe, Denise Sogg, Stephanie Friedman, Kelli E. TI Letter to the Editor: a Comparative Study of Three-Year Weight Loss and Outcomes After Laparoscopic Gastric Bypass in Patients with "Yellow Light" Psychological Clearance SO OBESITY SURGERY LA English DT Letter C1 [Ratcliffe, Denise] Chelsea & Westminster Hosp, Bariatr Surg Serv, London SW10 9NH, England. [Ratcliffe, Denise] CNWL NHS Fdn Trust, Psychol Med Unit, London SW10 9NG, England. [Ratcliffe, Denise] Phoenix Hlth, Chester, Cheshire, England. [Sogg, Stephanie] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Sogg, Stephanie] Harvard Univ, Sch Med, Boston, MA USA. [Friedman, Kelli E.] Duke Univ, Med Ctr, Duke Ctr Metab & Weight Loss Surg, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. RP Ratcliffe, D (reprint author), CNWL NHS Fdn Trust, Psychol Med Unit, London SW10 9NG, England. EM d.ratcliffe@nhs.net NR 2 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 EI 1708-0428 J9 OBES SURG JI Obes. Surg. PD MAR PY 2015 VL 25 IS 3 BP 539 EP 540 DI 10.1007/s11695-014-1445-1 PG 2 WC Surgery SC Surgery GA CD2GF UT WOS:000350892500023 PM 25287530 ER PT J AU Lefebvre, DR Yoon, MK AF Lefebvre, Daniel R. Yoon, Michael K. TI CT-Based Measurements of the Sphenoid Trigone in Different Sex and Race SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LATERAL ORBITAL WALL; DECOMPRESSION; VOLUME; BONE AB Purpose: In thyroid orbitopathy, surgical treatment of exophthalmos and compressive optic neuropathy is orbital decompression. Deep lateral wall decompression has been advocated alone or combined with the medial wall for a "balanced" decompression. The degree of lateral decompression is dependent on the volume of the sphenoid trigone comprising the deep lateral orbital wall. This study aims to compare the volume of the trigone in various races in men and women. Methods: After Institutional Review Board approval, patients with normal sinus CT scans (Siemens Somatom 40-slice) were retrospectively reviewed. Inclusion criteria were men and women aged 30 to 60 years, no orbital disease or surgery, normal orbital CT scans, and self-reported race (Asian, black/African American, white). Scans were measured with imaging software (Synapse, Fujifilm USA). The superior and inferior extents of the measured trigone were the superior and inferior orbital fissures, respectively. In the axial CT plane, the areas of each slice of the right and left trigone were manually outlined with the software and volume subsequently calculated based on the slice thickness (2 mm). Comparisons between groups were made via repeated measures analysis of variance. Results: One hundred twenty subjects were included, 20 from each subgroup, yielding 240 measured orbits. The overall volume of the sphenoid trigone for all groups combined was 1.53 cm(3) (standard deviation 0.72 cm(3)). Mean male volume was significantly larger than mean female volume (1.71 +/- 0.83 cm(3) vs. 1.35 +/- 0.55 cm(3); p = 0.004). Average left side volume was larger than paired right side volume (1.58 +/- 0.74 cm(3) vs. 1.49 +/- 0.71 cm(3); p = 0.02). There were no significant differences in average volumes between races (p = 0.17). Conclusions: The mean sphenoid trigone volume was larger in men than in women. There were no significant differences in volume between racial groups. The data showed significant interindividual and intraindividual variability. When analyzing these data for the purposes of orbital decompression, planning should be based on each side of each patient, as the expected degree of lateral decompression may vary greatly. C1 [Lefebvre, Daniel R.; Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Div Ophthalm Plast Surg, Boston, MA USA. [Lefebvre, Daniel R.; Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Lefebvre, DR (reprint author), Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg, 243 Charles St, Boston, MA 02114 USA. EM michael_yoon@meei.harvard.edu NR 11 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR-APR PY 2015 VL 31 IS 2 BP 155 EP 158 DI 10.1097/IOP.0000000000000370 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA CD1IM UT WOS:000350828300028 PM 25658833 ER PT J AU Pemberton, JD MacIntosh, PW Zeglam, A Fay, A AF Pemberton, John D. MacIntosh, Peter W. Zeglam, Ahmaida Fay, Aaron TI Naphazoline as a Confounder in the Diagnosis of Carotid Artery Dissection SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID PTOSIS AB Diagnosing Horner Syndrome can be difficult in the setting of an incomplete triad. A 27-year-old man presented with unilateral eyelid droop and intermittent ipsilateral headaches, having already seen 7 physicians. Physical examination revealed unilateral ptosis but no pupillary miosis or facial anhidrosis. Inspection of his clinical photographs revealed elevation of the ipsilateral lower eyelid, suggesting sympathetic dysfunction. On further questioning, he admitted to naphazoline dependence. Reexamination after ceasing the naphazoline unveiled the anisocoria. Vascular imaging subsequently revealed carotid dissection, and the patient was started on anticoagulant and antiplatelet therapy. The ptosis persisted after conjunctival Mullerectomy. External levator resection was recommended, but patient declined. This case underscores the importance of clinical photography, meticulous medical record review, and complete medication history including over-the-counter preparations. Clinicians should meticulously inspect the lower eyelid in cases of atypical blepharoptosis and consider the effects of eye drops when inspecting pupils for miosis. C1 [Pemberton, John D.; Zeglam, Ahmaida] Univ Arkansas Med Sci, Coll Med Div, Little Rock, AR 72205 USA. [Pemberton, John D.] Univ Arkansas Med Sci, Jones Eye Inst, Dept Ophthalmol, Little Rock, AR 72205 USA. [MacIntosh, Peter W.; Fay, Aaron] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Fay, Aaron] Massachusetts Eye & Ear Infirm, Dept Ophthalmol Ophthalm Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu OI Pemberton, John/0000-0001-6305-4653 NR 10 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 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR-APR PY 2015 VL 31 IS 2 BP E33 EP E35 DI 10.1097/IOP.0000000000000059 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA CD1IM UT WOS:000350828300004 PM 24807801 ER PT J AU Hajjarian, Z Nadkarni, SK AF Hajjarian, Zeinab Nadkarni, Seemantini K. TI Estimation of particle size variations for laser speckle rheology of materials SO OPTICS LETTERS LA English DT Article ID ATHEROSCLEROTIC PLAQUES; POLARIZED-LIGHT; TISSUE AB Laser speckle rheology (LSR) is an optical technique for assessing the viscoelastic properties of materials with several industrial, biological, and medical applications. In LSR, the viscoelastic modulus, G*(omega), of a material is quantified by analyzing the temporal fluctuations of speckle patterns. However, the size of scattering particles within the material also influences the rate of speckle fluctuations, independent of sample mechanical properties, and complicates the accurate estimation of G*(omega). Here, we demonstrate that the average particle size may be retrieved from the azimuth-angle dependence of time-averaged speckle intensities, permitting the accurate quantification of the viscoelastic moduli of materials with unknown particle size distribution using LSR. (C) 2015 Optical Society of America C1 [Nadkarni, Seemantini K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Nadkarni, SK (reprint author), Harvard Univ, Sch Med, 40 Blossom St,BAR 7, Boston, MA 02114 USA. EM snadkarni@mgh.harvard.edu FU National Institutes of Health [1RO1HL119867-01, U54 EB015408-01]; Air Force Office of Scientific Research AFOSR [FA9550-13-1-0068] FX The authors acknowledge the support from the National Institutes of Health 1RO1HL119867-01, U54 EB015408-01, and Air Force Office of Scientific Research AFOSR FA9550-13-1-0068 grants. NR 17 TC 5 Z9 5 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD MAR 1 PY 2015 VL 40 IS 5 BP 764 EP 767 DI 10.1364/OL.40.000764 PG 4 WC Optics SC Optics GA CD0YW UT WOS:000350801500022 PM 25723427 ER PT J AU Eisenberg, E Burstein, Y Suzan, E Treister, R Aviram, J AF Eisenberg, Elan Burstein, Yulia Suzan, Erica Treister, Roi Aviram, Joshua TI Spinal cord stimulation attenuates temporal summation in patients with neuropathic pain SO PAIN LA English DT Article DE Radicular pain; Dermatome; Wind-up; Quantitative sensory testing; Analgesia ID PROSPECTIVE MULTICENTER; DORSAL-HORN; FOLLOW-UP; TRIAL; MECHANISMS; THRESHOLD; ANALGESIA; MODEL AB Evidence has shown that electrical stimutatjon at the ciorsal columns attenuated the "wind-up" phenomenon in dorsal horn neurons in nerve-injured rats. This study was aimed to test the effect of spinal cord stimulation (SOS) on temporal summation (TS), the clinical correlate of the wind-up phenomenon in patients with radicular leg pain. Eighteen patients with SOS implants were tested both 30 minutes after SOS activation ("ON") and 2 hours 'after turning it off ("OFF"), in a random order. Temporal summation was evaluated in the most painful site in the affected leg and in the corresponding area in the contralateral leg by applying a tonic painful heat stimulus (46.5 degrees C; 120 seconds) and simultaneous recording of the perCeived heat pain intensity. Patients were also requested to report their clinical pain intensity (0-100 numerical pain scale) during SOS "ON" and "OFF". The Wilcoxon signed rank test was used in the comparisons between SOS "ON" and "OFF". Spinal cord stimulation activation significantly attenuated clinical pain intensity (from 66 +/- 18 to 27 +/- 31, P < 0.001). In the nonpainful leg, SOS activation failed to produce an effect on TS (24 +/- 20 vs 21 +/- 24 in SOS "OFF" and "ON", respectively; P = 0.277). In contrast, a significant decrease in the magnitude of TS in the affected leg was observed in response to SOS activation (from 32 +/- 33 to 19 +/- 24; P = 0.017). These results suggest that attenuation of, TS, which likely represents suppression of hyperexcitability in spinal cord neurons, is a possible mechanism underlying SOS analgesia in patients with neuropathic pain. C1 [Eisenberg, Elan; Suzan, Erica] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel. [Eisenberg, Elan] Rambam Hlth Care Campus, Inst Pain Med, IL-3109601 Haifa, Israel. [Burstein, Yulia] Hillel Yaffe Med Ctr, Dept Anesthesiol, Hadera, Israel. [Treister, Roi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Aviram, Joshua] Univ Haifa, Fac Social Welf & Hlth Sci, IL-31999 Haifa, Israel. RP Eisenberg, E (reprint author), Rambam Hlth Care Campus, Inst Pain Med, Pain Res Unit, POB 9602, IL-3109601 Haifa, Israel. EM e_eisenberg@rambam.health.gov.il NR 20 TC 2 Z9 2 U1 0 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 MAR PY 2015 VL 156 IS 3 BP 381 EP 385 DI 10.1097/01.j.pain.0000460342.69718.a2 PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CC7CW UT WOS:000350526300007 PM 25599230 ER PT J AU Liu, CQ Cholerton, B Shi, M Ginghina, C Cain, KC Auinger, P Zhang, J AF Liu, Changqin Cholerton, Brenna Shi, Min Ginghina, Carmen Cain, Kevin C. Auinger, Peggy Zhang, Jing CA Parkinson Study Grp DATATOP TI CSF tau and tau/A beta(42) predict cognitive decline in Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Biomarkers; Cerebrospinal fluid; Cognition; Neuropsychological tests; Parkinson disease; tau proteins ID CEREBROSPINAL-FLUID; AMYLOID-BETA; ALPHA-SYNUCLEIN; T-TAU; DEMENTIA; ASSOCIATION; PERFORMANCE; IMPAIRMENT; BIOMARKERS; MUTATIONS AB Introduction: A substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches. Methods: Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n = 403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n = 305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid beta(1-42) (A beta(42)), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype. Results: No association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/A beta(42) predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype. Conclusions: The current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Liu, Changqin; Shi, Min; Ginghina, Carmen; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Liu, Changqin] Xiamen Univ, Affiliated Hosp 1, Dept Endocrinol & Diabet, Xiamen, Peoples R China. [Cholerton, Brenna] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Cholerton, Brenna] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Cain, Kevin C.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98104 USA. [Auinger, Peggy] Univ Rochester, Sch Med & Dent, Dept Neurol, Ctr Human Expt Therapeut, Rochester, NY 14642 USA. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, HMC Box 359635,325 9th Ave, Seattle, WA 98104 USA. EM liuchangqin@126.com; bchol@uw.edu; mshi70@uw.edu; ginghina@uw.edu; cain@uw.edu; peggy.auinger@chet.rochester.edu; zhangj@uw.edu RI Shi, Min/G-6165-2012 OI Shi, Min/0000-0002-6901-2558 FU Michael J. Fox Foundation; NIH [AG10124, ES004696-5897, ES007033-6364, AG033398, ES016873, ES019277, NS057567, NS062684-6221, NS082137] FX The study is supported by generous grants from the Michael J. Fox Foundation as well as NIH (AG10124, ES004696-5897, ES007033-6364, AG033398, ES016873, ES019277, NS057567, NS062684-6221 and NS082137). We thank Karen Marder, Lorraine Clark, and the Parkinson's Disease Foundation Weill Family Fund for providing the APOE data for this study. NR 29 TC 16 Z9 17 U1 0 U2 9 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 MAR PY 2015 VL 21 IS 3 BP 271 EP 276 DI 10.1016/j.parkreldis.2014.12.027 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CD2SU UT WOS:000350930100019 PM 25596881 ER PT J AU Fang, JY Perez, A Christine, CW Leehey, M Aminoff, MJ Boyd, JT Morgan, JC Dhall, R Nicholas, AP Bodis-Wollner, I Zweig, RM Goudreau, JL AF Fang, John Y. Perez, Adriana Christine, Chadwick W. Leehey, Maureen Aminoff, Michael J. Boyd, James T. Morgan, John C. Dhall, Rohit Nicholas, Anthony P. Bodis-Wollner, Ivan Zweig, Richard M. Goudreau, John L. CA NINDS NET-PD Investigators TI Parkinson's disease severity and use of dopaminergic medications SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Levodopa; Dopamine agonist; Clinical trial; Disability; Cognition ID TRIAL; LEVODOPA; DESIGN AB Background: The effects of dopaminergic therapy in parkinson's disease (PD) can vary depending on the class of medication selected. Objective: The aim of this post hoc study was to determine if the class of dopaminergic therapy correlated with disease severity in persons with early, treated PD. Methods: A non-parametric global statistical test (GST) was used to assess the status of participants treated with dopamine agonist (DA) monotherapy, levodopa (LD) monotherapy or combined LD and DA therapy on multiple PD outcomes encompassing motor, cognitive, psychiatric and autonomic function, as well as disability and quality of life. Results: The outcomes measured at the beginning of the study showed lower disease burden for participants on initial DA monotherapy compared to those taking combined LD and DA therapy after controlling for age, education, taking cog-meds and amantadine. Conclusion: This observation suggests that clinicians treating early PD patients favor combined LD and DA therapy in patients with more disabling features over DA monotherapy. As such, studies of PD progression in treated PD patients may be affected by the class of symptomatic dopaminergic therapy. Published by Elsevier Ltd. C1 [Fang, John Y.] Vanderbilt Univ, Dept Neurol, Nashville, TN 37232 USA. [Perez, Adriana] Univ Texas Sch Publ Hlth, UTHlth, Austin, TX 78701 USA. [Christine, Chadwick W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Leehey, Maureen] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA. [Aminoff, Michael J.] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA. [Boyd, James T.] Univ Vermont, Dept Neurol Sci, Coll Med, Burlington, VT 05401 USA. [Morgan, John C.] Georgia Regents Univ, Dept Neurol, Med Coll Georgia, Movement & Cognit Disorders Ctr, Augusta, GA 30912 USA. [Dhall, Rohit] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Nicholas, Anthony P.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Nicholas, Anthony P.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Bodis-Wollner, Ivan] Suny Downstate Med Ctr, Dept Neurol, Brooklyn, NY 11203 USA. [Bodis-Wollner, Ivan] Suny Downstate Med Ctr, Dept Ophthalmol, Brooklyn, NY 11203 USA. [Zweig, Richard M.] LSU Hlth Sci Ctr Shreveport, Dept Neurol, Shreveport, LA 71130 USA. [Goudreau, John L.] Michigan State Univ, Dept Neurol, E Lansing, MI 48824 USA. RP Fang, JY (reprint author), Vanderbilt Univ, Dept Neurol, 1161 21st Ave South,A-0118, Nashville, TN 37232 USA. EM john.y.fang@vanderbilt.edu FU NIMHD NIH HHS [R24 MD001779]; NINDS NIH HHS [U10 NS044555] NR 7 TC 1 Z9 1 U1 0 U2 6 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 MAR PY 2015 VL 21 IS 3 BP 297 EP 299 DI 10.1016/j.parkreldis.2014.10.016 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA CD2SU UT WOS:000350930100024 PM 25541182 ER PT J AU Speltz, ML Birgfeld, C Starr, JR Collett, B Kapp-Simon, K AF Speltz, Matthew L. Birgfeld, Craig Starr, Jacqueline R. Collett, Brent Kapp-Simon, Kathleen TI The Effects of Whole-Vault Cranioplasty versus Strip Craniectomy on Long-Term Neuropsychological Outcomes in Sagittal Craniosynostosis SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter ID SINGLE-SUTURE CRANIOSYNOSTOSIS; INFANTS C1 [Speltz, Matthew L.; Birgfeld, Craig; Collett, Brent] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Starr, Jacqueline R.] Forsyth Inst, Cambridge, MA USA. [Kapp-Simon, Kathleen] Shriners Hosp Children, Chicago, IL USA. [Kapp-Simon, Kathleen] Univ Illinois, Chicago, IL USA. RP Speltz, ML (reprint author), Univ Washington, Sch Med, Box 359300, Seattle, WA 98195 USA. EM matt.speltz@seattlechildrens.org NR 5 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 2015 VL 135 IS 3 BP 646E EP 647E DI 10.1097/PRS.0000000000001067 PG 3 WC Surgery SC Surgery GA CD0IO UT WOS:000350754700026 PM 25647708 ER PT J AU Brezing, C Ferrara, M Freudenreich, O AF Brezing, Christina Ferrara, Maria Freudenreich, Oliver TI The Syndemic Illness of HIV and Trauma: Implications for a Trauma-Informed Model of Care SO PSYCHOSOMATICS LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; SUBSTANCE USE DISORDER; SEVERE MENTAL-ILLNESS; AFRICAN-AMERICAN MEN; RISK BEHAVIOR; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; HEALTH OUTCOMES; POSITIVE WOMEN AB Background: People living with HIV infection are disproportionately burdened by trauma and the resultant negative health consequences, making the combiin of HIV infection and trauma a syndemic illness. Despite the high co-occurrence and negative influence on health, trauma and posttrattmatic sequelae in people living with HIV infection often go unrecognized and untreated because of the current gaps in medical training and lack at practice guidelines, Objective: We set out to review the current literature on HIV infection and trauma and propose a trauma-informed model of care to target this,syndemic illness. Methods: We searched PubMed, PsycINFO, and Cochrane review databases for articles that contained the following search terms: HIV AND either trauma (specifically violent trauma), PTSD intimate partner violence (IPV) abuse, or trauma-informed care. Articles were limited to primary clinical research or metanalyses published in English, Articles were excluded if they referred to HIV-associated posttraumatic stress disorder or HIV-associated posttraumatic growth. Results: We confirm high, but variable, rates of trauma in people living with HIV infection demonstrated in multiple studies, ranging from 10%-90%. Trauma is associated with (1) increased HIV-risk behavior, contributing to transmission and acquisition of the virus; (2) negative internal and external mediators also associated with poor health and high-risk HIV behavior; (3) poor adherence to treatment; (4) poor HI V-related and other health outcomes; and (5) particularly vulnerable special populations. Conclusions: Clinicians should consider using a model of trauma-informed care in the treatment of people living with HIV infection. Its adoption in different settings needs to be matched to available resources. C1 [Brezing, Christina] Columbia Univ, Coll Phys & Surg, Div Subst Abuse, Dept Psychiat, New York, NY 10032 USA. [Ferrara, Maria] AUSL Modena, Dept Mental Hlth & Subst Abuse, Modena, Italy. [Freudenreich, Oliver] Massachusetts Gen Hosp, Dept Psychiat, Div Med & Psychiat, Boston, MA 02114 USA. RP Brezing, C (reprint author), Columbia Univ, Coll Phys & Surg, Div Subst Abuse, Dept Psychiat, 1051 Riverside Dr,Unit 66,Rm 3736, New York, NY 10032 USA. EM brezing@nyspi.columbia.edu NR 91 TC 11 Z9 11 U1 4 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2015 VL 56 IS 2 BP 107 EP 118 PG 12 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CD0BO UT WOS:000350735400001 PM 25597836 ER PT J AU Suarez, L Beach, SR Moore, SV Mastromauro, CA Januzzi, JL Celano, CM Chang, TE Huffman, JC AF Suarez, Laura Beach, Scott R. Moore, Shannon V. Mastromauro, Carol A. Januzzi, James L. Celano, Christopher M. Chang, Trina E. Huffman, Jeff C. TI Use of the Patient Health Questionnaire-9 and a Detailed Suicide Evaluation in Determining Imminent Suicidality in Distressed Patients With Cardiac Disease SO PSYCHOSOMATICS LA English DT Article ID DEATH REPORTING SYSTEM; CORONARY-HEART-DISEASE; PRIMARY-CARE; MYOCARDIAL-INFARCTION; DEPRESSION SCREENER; ATRIAL-FIBRILLATION; ANXIETY DISORDERS; CANCER-PATIENTS; RISK-ASSESSMENT; IDEATION AB Background: The risk of suicide is elevated in patients with cardiac disease in comparison with the general population. Objective: In distressed cardiac inpatients, we explored the use of Item 9 of the Patient Health Questionnaire-9, which inquires about thoughts of death or suicide, and a detailed suicide evaluation (DSE) triggered by positive responses to Item 9 as means of assessing suicide. Methods: Among cardiac inpatients endorsing current emotional distress, we recorded the prevalence of positive responses to item 9, gathered information about outcomes and time spent completing the DSE, and examined the frequency of imminent suicidality identified by the DSE among Item 9-positive patients. Results: Among 366 patients, 77 (21%) answered affirmatively to Item 9. All DSEs were successfully completed but consumed 17 clinician hours. Among the 71 patients receiving the DSE, 2 (0.5% of total sample; 2.8% of Item 9-positive patients) were imminently suicidal (i.e., had intent or plan). Conclusion: Nearly I in 4 patients had a positive response to Item 9, but very few had imminent suicidality; the DSE was easy to use and acceptable to patients but time consuming. A more narrowly focused alternative to Item 9 may more accurately predict imminent,suicidality and reduce the burden of further detailed suicide screening. C1 [Suarez, Laura; Beach, Scott R.; Moore, Shannon V.; Mastromauro, Carol A.; Januzzi, James L.; Celano, Christopher M.; Chang, Trina E.; Huffman, Jeff C.] Harvard Univ, Sch Med, Boston, MA USA. [Suarez, Laura; Beach, Scott R.; Moore, Shannon V.; Mastromauro, Carol A.; Celano, Christopher M.; Chang, Trina E.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Beach, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 605, Boston, MA 02114 USA. EM sbeach1@partners.org FU American Heart Association, USA [10GRNT3450015] FX This research was funded by an American Heart Association, USA Grant-in-Aid 10GRNT3450015 (Huffman): the funders had no role in the acquisition, analysis, or interpretation of data. NR 42 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2015 VL 56 IS 2 BP 181 EP 189 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CD0BO UT WOS:000350735400007 PM 25660436 ER PT J AU Rustad, JK Cho, T Chemali, Z Rost, N Stern, TA AF Rustad, James K. Cho, Tracey Chemali, Zeina Rost, Natalia Stern, Theodore A. TI The Recognition and Treatment of Rabies: A Case Report and Discussion SO PSYCHOSOMATICS LA English DT Editorial Material ID ENCEPHALITIS; DIAGNOSIS; CHOKING; FEAR C1 [Rustad, James K.] Univ S Florida, Morsani Coll Med, Tampa, FL 33613 USA. [Cho, Tracey; Chemali, Zeina; Rost, Natalia; Stern, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Rustad, JK (reprint author), Univ S Florida, Morsani Coll Med, Dept Psychiat & Behav Neurosci, 3515 E Fletcher Ave, Tampa, FL 33613 USA. EM jkrustad@health.usf.edu NR 24 TC 0 Z9 0 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2015 VL 56 IS 2 BP 196 EP 201 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CD0BO UT WOS:000350735400009 PM 25591495 ER PT J AU Greene, ME Rolfson, O Garellick, G Gordon, M Nemes, S AF Greene, M. E. Rolfson, O. Garellick, G. Gordon, M. Nemes, S. TI Improved statistical analysis of pre- and post-treatment patient-reported outcome measures (PROMs): the applicability of piecewise linear regression splines SO QUALITY OF LIFE RESEARCH LA English DT Article DE EQ-5D; Segmented regression; Change point; Total hip arthroplasty ID 2 SEPARATE REGIMES; 2-PHASE REGRESSION; CROSS-VALIDATION; HIP-REPLACEMENT; CHANGE-POINTS; INFERENCE; MODELS; CANCER; LIKELIHOOD; TESTS AB Patient-reported health-related quality-of-life (HRQoL) measures such as the EuroQol 5 dimension (EQ-5D) index are commonplace when assessing healthcare providers or efficiency of medical techniques. HRQoL measures are generally bounded, and the magnitude of possible improvement depends on the pre-treatment HRQoL value. This paper aimed to assess and illustrated the possibility of modelling the relationship between pre- and post-treatment HRQoL measures with piecewise linear splines. The method was illustrated using a longitudinal dataset of 36,625 patients with one EQ-5D index before and one a year after total hip arthroplasty. We considered four models: intercept only model, single line regression, and segmented regression with 1 and 2 change points. The post-operative EQ-5D index served as the outcome, while the preoperative EQ-5D index was the predictor. We found that a two-line regression best described the data with the lines meeting at 0.159 on the preoperative EQ-5D index scale. In the low preoperative group (with an initial preoperative index from -0.594 to 0.159), the predicted post-operative scores ranged from 0.368 to 0.765, with post-operative scores increasing 0.528 points for each unit in the preoperative score. In the high preoperative group (initial range from 0.159 to 1), the predicted post-operative scores ranged from 0.765 to 0.855, increasing 0.106 points for each unit in the preoperative score. Piecewise linear regression is a straightforward approach to analyse baseline and follow-up HRQoL measures such as the EQ-5D index. It can provide a reasonable approximation of the shape of the underlying relationship where the threshold and slopes prove informative and meaningful. C1 [Greene, M. E.; Rolfson, O.; Garellick, G.; Gordon, M.; Nemes, S.] Ctr Registers Vastra Gotaland, Swedish Hip Arthroplasty Register, S-41345 Gothenburg, Sweden. [Greene, M. E.; Rolfson, O.; Garellick, G.; Nemes, S.] Univ Gothenburg, Dept Orthoped, Inst Clin Sci, Sahlgrenska Acad, S-41345 Gothenburg, Sweden. [Greene, M. E.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Gordon, M.] Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden. RP Nemes, S (reprint author), Ctr Registers Vastra Gotaland, Swedish Hip Arthroplasty Register, Medicinargatan 18G, S-41345 Gothenburg, Sweden. EM szilard.nemes@registercentrum.se RI Gordon, Max/M-4330-2014; OI Gordon, Max/0000-0002-8080-5815; Nemes, Szilard/0000-0002-4145-1786; Rolfson, Ola/0000-0001-6534-1242 FU Swedish National Board of Health and Welfare; Swedish Association of Local Authorities and Regions; County Council of the Western Region of Sweden; Dr Felix Neuberghs Foundation FX This study is an analysis of the databases in the Swedish Hip Arthroplasty Register, which is funded by the Swedish National Board of Health and Welfare, the Swedish Association of Local Authorities and Regions and the County Council of the Western Region of Sweden. Research grants from Dr Felix Neuberghs Foundation have contributed financially to this study. The publication of the results is not contingent on the sponsor's approval. NR 39 TC 6 Z9 6 U1 1 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD MAR PY 2015 VL 24 IS 3 BP 567 EP 573 DI 10.1007/s11136-014-0808-3 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CC9MO UT WOS:000350694900006 PM 25252607 ER PT J AU Watt, T Barbesino, G Bjorner, JB Bonnema, SJ Bukvic, B Drummond, R Groenvold, M Hegedus, L Kantzer, V Lasch, KE Marcocci, C Mishra, A Netea-Maier, R Ekker, M Paunovic, I Quinn, TJ Rasmussen, AK Russell, A Sabaretnam, M Smit, J Torring, O Zivaljevic, V Feldt-Rasmussen, U AF Watt, Torquil Barbesino, Giuseppe Bjorner, Jakob Bue Bonnema, Steen Joop Bukvic, Branka Drummond, Russell Groenvold, Mogens Hegedus, Laszlo Kantzer, Valeska Lasch, Kathryn E. Marcocci, Claudio Mishra, Anjali Netea-Maier, Romana Ekker, Merel Paunovic, Ivan Quinn, Terence J. Rasmussen, Ase Krogh Russell, Audrey Sabaretnam, Mayilvaganan Smit, Johannes Torring, Ove Zivaljevic, Vladan Feldt-Rasmussen, Ulla TI Cross-cultural validity of the thyroid-specific quality-of-life patient-reported outcome measure, ThyPRO SO QUALITY OF LIFE RESEARCH LA English DT Article DE Thyroid diseases; Quality of life; Patient-reported outcome measure; Cross-cultural validity; Differential item functioning ID ORDINAL LOGISTIC-REGRESSION; ITEM FUNCTIONING DETECTION; EFFECT SIZE; CONSTRUCT-VALIDITY; HEALTH OUTCOMES; GRAVES-DISEASE; QUESTIONNAIRE; IMPACT; CALIBRATION; DISORDERS AB Thyroid diseases are common and often affect quality of life (QoL). No cross-culturally validated patient-reported outcome measuring thyroid-related QoL is available. The purpose of the present study was to test the cross-cultural validity of the newly developed thyroid-related patient-reported outcome ThyPRO, using tests for differential item functioning (DIF) according to language version. The ThyPRO consists of 85 items summarized in 13 multi-item scales and one single item. Scales cover physical and mental symptoms, well-being and function as well as social and daily function and cosmetic concerns. Translation applied standard forward-backward methodology with subsequent cognitive interviews and reviews. Responses (N = 1,810) to the ThyPRO were collected in seven countries: UK (n = 166), The Netherlands (n = 147), Serbia (n = 150), Italy (n = 110), India (n = 148), Denmark (n = 902) and Sweden (n = 187). Translated versions were compared pairwise to the English version by examining uniform and nonuniform DIF, i.e., whether patients from different countries respond differently to a particular item, although they have identical level of the concept measured by the item. Analyses were controlled for thyroid diagnosis. DIF was investigated by ordinal logistic regression, testing for both statistical significance and magnitude (Delta R (2) > 0.02). Scale level was estimated by the sum score, after purification. For twelve of the 84 tested items, DIF was identified in more than one language. Eight of these were small, but four were indicative of possible low translatability. Twenty-one instances of DIF in single languages were identified, indicating potential problems with the particular translation. However, only seven were of a magnitude which could affect scale scores, most of which could be explained by sample differences not controlled for. The ThyPRO has good cross-cultural validity with only minor cross-cultural invariance and is recommended for use in international multicenter studies. C1 [Watt, Torquil; Rasmussen, Ase Krogh; Feldt-Rasmussen, Ulla] Univ Copenhagen, Dept Endocrinol, Hosp Rigshospitalet, DK-2100 Copenhagen O, Denmark. [Barbesino, Giuseppe] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bjorner, Jakob Bue] QualityMetric, Lincoln, RI USA. [Bonnema, Steen Joop; Hegedus, Laszlo] Odense Univ Hosp, Dept Endocrinol & Metab, DK-5000 Odense, Denmark. [Bukvic, Branka; Paunovic, Ivan; Zivaljevic, Vladan] Clin Ctr Serbia, Belgrade, Serbia. [Drummond, Russell; Quinn, Terence J.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Groenvold, Mogens] Univ Copenhagen, Res Unit, Dept Palliat Med, Bispebjerg Hosp, DK-2100 Copenhagen O, Denmark. [Groenvold, Mogens] Univ Copenhagen, Dept Hlth Serv Res, DK-2100 Copenhagen O, Denmark. [Kantzer, Valeska] Hlth Res Associates Inc, Mountlake Terrace, WA USA. [Lasch, Kathryn E.] Pharmerit Int, Bethesda, MD USA. [Marcocci, Claudio] Univ Pisa, Univ Dept Clin & Expt Med, Pisa, Italy. [Marcocci, Claudio] Univ Hosp Pisa, Endocrine Unit 2, Pisa, Italy. [Mishra, Anjali] Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India. [Netea-Maier, Romana; Ekker, Merel; Smit, Johannes] Radboud Univ Nijmegen Med Ctr, Dept Internal Med, Nijmegen, Netherlands. [Russell, Audrey] Natl Univ Ireland Univ Coll Cork, Cork, Ireland. [Sabaretnam, Mayilvaganan] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Torring, Ove] Karolinska Inst Sodersjukhuset, Inst Clin Sci & Educ, Stockholm, Sweden. RP Watt, T (reprint author), Univ Copenhagen, Dept Endocrinol, Hosp Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. EM torquil.watt@regionh.dk RI Netea, Mihai/N-5155-2014; Smit, J.W.A./H-8091-2014; Netea-Maier, R.T./L-4543-2015; OI Gronvold, Mogens/0000-0002-3153-780X FU Danish Agency for Science, Technology and Innovation: Council for Strategic Research and Council for Independent Research; Genzyme Corporation FX This study has been supported by grants from the Danish Agency for Science, Technology and Innovation: Council for Strategic Research and Council for Independent Research and by Genzyme Corporation by an unrestricted research grant. Special thanks to Sabrina Sereni, Supriya Mathur, Kajsa Bergman, Gitte Karina Geil, Kim AEbelo, Selma Flora Watt and Laura Siim Magnussen for assistance with data entry and logistics. NR 50 TC 6 Z9 6 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD MAR PY 2015 VL 24 IS 3 BP 769 EP 780 DI 10.1007/s11136-014-0798-1 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CC9MO UT WOS:000350694900025 PM 25194574 ER PT J AU Vargas, M Servillo, G Tessitore, G Aloj, F Brunetti, I Arditi, E Salami, D Kacmarek, RM Pelosi, P AF Vargas, Maria Servillo, Giuseppe Tessitore, Gaetano Aloj, Fulvio Brunetti, Iole Arditi, Enrico Salami, Dorino Kacmarek, Robert M. Pelosi, Paolo TI Double Lumen Endotracheal Tube for Percutaneous Tracheostomy-Reply SO RESPIRATORY CARE LA English DT Letter C1 [Vargas, Maria; Servillo, Giuseppe; Tessitore, Gaetano] Univ Naples Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, Naples, Italy. [Aloj, Fulvio] Ist Ricovero & Cura Carattere Sci Neuromed, Anaesthesia & Intens Care Unit, Pozzilli, Italy. [Brunetti, Iole; Arditi, Enrico; Salami, Dorino] Univ Genoa, Dept Anesthesia & Intens Care, Azienda Osped Univ San Martino IST, Ist Ricovero & Cura Carattere Sci, Genoa, Italy. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. [Pelosi, Paolo] Univ Genoa, Azienda Osped Univ San Martino IST, Ist Ricovero & Cura Carrattere Sci, Dept Anesthesia & Intens Care,Dept Surg Sci & Int, Genoa, Italy. 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 3 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 MAR PY 2015 VL 60 IS 3 BP E62 EP E63 DI 10.4187/respcare.04009 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CD2IB UT WOS:000350898700030 PM 25737577 ER PT J AU Dedania, VS Grob, S Zhang, K Bakri, SJ AF Dedania, Vaidehi S. Grob, Seanna Zhang, Kang Bakri, Sophie J. TI PHARMACOGENOMICS OF RESPONSE TO ANTI-VEGF THERAPY IN EXUDATIVE AGE-RELATED MACULAR DEGENERATION SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Review DE age-related macular degeneration; ARMS2; bevacizumab; complement factor H (CFH); eye; genetics; HTRA1; ranibizumab; retina; single-nucleotide polymorphisms; vascular endothelial growth factor ID COMPLEMENT FACTOR-H; ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL RANIBIZUMAB; PIGMENT EPITHELIUM; BEVACIZUMAB; RISK; ASSOCIATION; GENE; SUSCEPTIBILITY; VARIANT AB Purpose: To determine whether there is an association between response to intravitreal anti-vascular endothelial growth factor agents and genotype in patients with neovascular age-related macular degeneration. Methods: Analysis of the current literature evaluating pharmacogenetics of treatment response in patients with neovascular age-related macular degeneration. Results: Studies have demonstrated associations between various genotypes and response to intravitreal anti-vascular endothelial growth factor agents. Lower-risk genotypes of the CFH, ARMS2, HTRA1, and VEGF-A genes may be associated with improved visual outcomes. Additionally, frequency of injections may be associated with certain genotypes. Conclusion: Genetic background may influence an individual's response to treatment of neovascular age-related macular degeneration. Further studies to investigate biologic pathways of neovascular age-related macular degeneration and gene products that are directly involved might lead to better understanding of contribution of various genes to treatment response. C1 [Dedania, Vaidehi S.] Albany Med Ctr, Lions Eye Inst, Albany, NY USA. [Grob, Seanna] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Grob, Seanna; Zhang, Kang] Univ Calif San Diego, Shiley Eye Ctr, Inst Genom Med, Dept Ophthalmol, La Jolla, CA 92093 USA. [Bakri, Sophie J.] Mayo Clin, Dept Ophthalmol, Rochester, MN USA. RP Bakri, SJ (reprint author), Mayo Clin, Dept Ophthalmol, Rochester, MN 55905 USA. EM bakri.sophie@mayo.edu FU Research to Prevent Blindness, New York, New York FX Supported by Research to Prevent Blindness, New York, New York (S.J.B.). NR 42 TC 4 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD MAR PY 2015 VL 35 IS 3 BP 381 EP 391 PG 11 WC Ophthalmology SC Ophthalmology GA CC4AO UT WOS:000350293100013 PM 25635578 ER PT J AU Pang, CE Sarraf, D Freund, KB AF Pang, Claudine E. Sarraf, David Freund, K. Bailey TI EXTREME CHOROIDAL THINNING IN HIGH MYOPIA SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE extreme choroidal thinning; leptochoroid; high myopia; subfoveal choroidal thickness; retinal thickness; visual acuity; age-related choroidal atrophy ID OPTICAL COHERENCE TOMOGRAPHY; THICKNESS MEASUREMENTS; AXIAL LENGTH; POSTERIOR STAPHYLOMA; RETINAL-DETACHMENT; VISUAL IMPAIRMENT; BEIJING EYE; LOW-VISION; BLINDNESS; POPULATION AB Purpose: To describe the spectral domain optical coherence tomography characteristics of extreme choroidal thinning in high myopia and demonstrate its compatibility with good visual acuity. Methods: This was a retrospective observational case review of nonconsecutive myopic patients with extreme choroidal thinning, defined as a subfoveal choroidal thickness of 20 mm or less as measured with spectral domain optical coherence tomography. Clinical features, such as visual acuity, axial length, and spectral domain optical coherence tomography characteristics including choroidal and retinal thicknesses in four quadrants were analyzed. Results: Thirty-six eyes of 20 patients with extreme choroidal thinning were included. Mean subfoveal choroidal thickness was 13.9 +/- 6.0 mu m, mean age was 71 years (range, 32-85 years), mean axial length was 30.7 +/- 2.2 mm, and mean follow-up duration was 44.7 +/- 15.4 months. Of these, 25 eyes (70%) had visual acuity of 20/40 or better (mean visual acuity was 20/30), whereas the remaining eyes had mean visual acuity of 20/193. All eyes with extreme choroidal thinning had prominent choroidal vessels seen under the macula documented on color fundus photography and near-infrared reflectance imaging. All eyes with visual acuity poorer than 20/40 had fovea-involving choroidal neovascularization and/or atrophy. In the 25 eyes with good visual acuity, the mean choroidal thickness was thinnest at the nasal zone, followed by inferior, superior, and temporal zones (P = 0.01); and there was no detectable decrease in choroidal thickness over time. The mean retinal thickness was thinner in the fovea and parafoveal zones when compared with highly myopic eyes without extreme choroidal thinning. Conclusion: Extreme choroidal thinning in myopic eyes is compatible with good visual acuity of 20/40 or better, may be present in a wide age range, and may not demonstrate any progressive decline over up to 70 months of follow-up; suggesting that choroidal thickness alone is not a reliable indicator of visual function. C1 [Pang, Claudine E.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA. [Pang, Claudine E.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY USA. [Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90024 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Freund, K. Bailey] NYU, Dept Ophthalmol, Sch Med, New York, NY 10016 USA. RP Pang, CE (reprint author), Vitreous Retina Macula Consultants New York, 460 Pk Ave,Fifth Floor, New York, NY 10022 USA. EM kbfnyf@aol.com FU LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, NY; Macula Foundation, Inc, New York, NY; Regeneron; Heidelberg; Genentech FX Supported by LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, NY and the Macula Foundation, Inc, New York, NY.; K. B. Freund is a consultant at Genentech, Regeneron, Optos, Bayer HealthCare, Thrombogneics, and Heidelberg Engineering. D. Sarraf has received research support from Regeneron and Heidelberg, and is a speaker. C. E. Pang has no financial/conflicting interests to disclose. D. Sarraf has received research support from Regeneron and Genentech, and is a consultant for Genentech. NR 47 TC 6 Z9 6 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD MAR PY 2015 VL 35 IS 3 BP 407 EP 415 PG 9 WC Ophthalmology SC Ophthalmology GA CC4AO UT WOS:000350293100016 PM 25313711 ER PT J AU Daskalakis, NP Binder, EB AF Daskalakis, Nikolaos P. Binder, Elisabeth B. TI Schizophrenia in the Spectrum of Gene-Stress Interactions: The FKBP5 Example SO SCHIZOPHRENIA BULLETIN LA English DT Article ID PITUITARY-ADRENAL AXIS; RECEPTOR MESSENGER-RNA; EARLY-LIFE ADVERSITY; CHILDHOOD TRAUMA; BIPOLAR DISORDER; ENVIRONMENT INTERACTIONS; PSYCHOSOCIAL STRESS; HIPPOCAMPAL VOLUME; CORTISOL-LEVELS; 1ST-EPISODE PSYCHOSIS AB Many studies have demonstrated that genotype (G) interacts with adverse life experiences (E) to produce individual differences in vulnerability and resilience to mental disorders, including schizophrenia. Genetic susceptibility to stress and the timing of the environmental exposure(s) are relevant for these interactions and represent common risk factors. We take the example of the FKBP5 gene to illustrate G x E interactions that predict pleiotropic psychiatric outcomes, including schizophrenia. C1 [Daskalakis, Nikolaos P.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Daskalakis, Nikolaos P.] James J Peters Vet Affairs Med Ctr, Mental Hlth Care Ctr, Bronx, NY USA. [Binder, Elisabeth B.] Max Planck Inst Psychiat, Dept Translat Res Psychiat, D-80804 Munich, Germany. [Binder, Elisabeth B.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. RP Daskalakis, NP (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM nikolaos.daskalakis@mssm.edu RI Daskalakis, Nikolaos/B-7930-2014 OI Daskalakis, Nikolaos/0000-0003-1660-9112 FU Dutch Top-Institute Pharma [T5-209] FX NPD was supported by the Dutch Top-Institute Pharma T5-209. EBB is co-inventor of the following patent application: "FKBP5: a novel target for antidepressant therapy. European Patent# EP 1687443 B1." The authors have declared that there are no other conflicts of interest in relation to the subject of this study. NR 91 TC 3 Z9 3 U1 4 U2 13 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 MAR PY 2015 VL 41 IS 2 BP 323 EP 329 DI 10.1093/schbul/sbu189 PG 7 WC Psychiatry SC Psychiatry GA CD3LI UT WOS:000350979500005 PM 25592294 ER PT J AU Perkins, DO Jeffries, CD Addington, J Bearden, CE Cadenhead, KS Cannon, TD Cornblatt, BA Mathalon, DH McGlashan, TH Seidman, LJ Tsuang, MT Walker, EF Woods, SW Heinssen, R AF Perkins, Diana O. Jeffries, Clark D. Addington, Jean Bearden, Carrie E. Cadenhead, Kristin S. Cannon, Tyrone D. Cornblatt, Barbara A. Mathalon, Daniel H. McGlashan, Thomas H. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. Woods, Scott W. Heinssen, Robert TI Towards a Psychosis Risk Blood Diagnostic for Persons Experiencing High-Risk Symptoms: Preliminary Results From the NAPLS Project SO SCHIZOPHRENIA BULLETIN LA English DT Article DE clinical high risk; psychosis; prodrome; multiplex; risk prediction; malondialdehyde-modified low-density lipoprotein (MDA-LDL); immune; inflammation; oxidative stress ID HIGH-CLINICAL-RISK; OXIDATIVE STRESS; CORTISOL SECRETION; GROWTH-FACTOR; ROC CURVE; AT-RISK; SCHIZOPHRENIA; METAANALYSIS; VALIDATION; PRODROME AB Introduction: A barrier to preventative treatments for psychosis is the absence of accurate identification of persons at highest risk. A blood test that could substantially increase diagnostic accuracy would enhance development of psychosis prevention interventions. Methods: The North American Prodrome Longitudinal Study project is a multisite endeavor that aims to better understand predictors and mechanisms for the development of psychosis. In this study, we measured expression of plasma analytes reflecting inflammation, oxidative stress, hormones, and metabolism. A "greedy algorithm" selected analytes that best distinguished persons with clinical high-risk symptoms who developed psychosis (CHR-P; n = 32) from unaffected comparison (UC) subjects (n = 35) and from those who did not develop psychosis during a 2-year follow-up (CHR-NP; n = 40). Results: The classifier included 15 analytes (selected from 117), with an area under the receiver operating curve for CHR-P vs UC of 0.91 and CHR-P vs CHR-NP of 0.88. Randomly scrambled group membership followed by reconstructions of the entire classifier method yielded consistently weak classifiers, indicating that the true classifier is highly unlikely to be a chance occurrence. Such randomization methods robustly imply the assays contain consistent information distinguishing the groups which was not obscured by the data normalization method and was revealed by classifier construction. These results support the hypothesis that inflammation, oxidative stress, and dysregulation of hypothalamic-pituitary axes may be prominent in the earliest stages of psychosis. Conclusion: If confirmed in other groups of persons at elevated risk of psychosis, a multiplex blood assay has the potential for high clinical utility. C1 [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Jeffries, Clark D.] Univ N Carolina, Renaissance Comp Inst, Chapel Hill, NC USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cadenhead, Kristin S.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Cannon, Tyrone D.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Cannon, Tyrone D.; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, Inst Genom Med, La Jolla, CA 92093 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Heinssen, Robert] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Perkins, DO (reprint author), Univ N Carolina, Dept Psychiat, CB 7160, Chapel Hill, NC 27599 USA. EM diana_perkins@med.unc.edu FU National Institute of Mental Health [U01MH0818902, U01MH081984, P50MH066286, U01MH082022, U01MH081857, U01MH082004, U01MH081928, U01MH081988, U01MH066160]; San Francisco Foundation FX National Institute of Mental Health grants (U01MH0818902 to T.D.C., U01MH081984 to J.M.A., P50MH066286 to C.E.B., U01MH082022 to K.S.C., U01MH081857 to B.A.C., U01MH082004 to D.O.P., U01MH081928 to L.J.S., U01MH081988 to E.F.W., U01MH066160 to S.W.W.). The analysis of plasma samples was funded by a gift from an anonymous donor administered through the San Francisco Foundation (Perkins). NR 58 TC 36 Z9 36 U1 4 U2 13 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 MAR PY 2015 VL 41 IS 2 BP 419 EP 428 DI 10.1093/schbul/sbu099 PG 10 WC Psychiatry SC Psychiatry GA CD3LI UT WOS:000350979500017 PM 25103207 ER PT J AU Oribe, N Hirano, Y Kanba, S del Re, E Seidman, L Mesholam-Gately, R Goldstein, JM Shenton, M Spencer, KM McCarley, RW Niznikiewicz, M AF Oribe, Naoya Hirano, Yoji Kanba, Shigenobu del Re, Elisabetta Seidman, Larry Mesholam-Gately, Raquelle Goldstein, Jill M. Shenton, Martha Spencer, Kevin M. McCarley, Robert W. Niznikiewicz, Margaret TI Progressive Reduction of Visual P300 Amplitude in Patients With First-Episode Schizophrenia: An ERP Study SO SCHIZOPHRENIA BULLETIN LA English DT Article DE EEG; first-episode schizophrenia; P300; longitudinal; progression of schizophrenia ID EVENT-RELATED POTENTIALS; GRAY-MATTER VOLUME; SUPERIOR TEMPORAL GYRUS; MISMATCH NEGATIVITY; PROCESSING DEFICITS; ONSET SCHIZOPHRENIA; LONGITUDINAL MRI; BRAIN; ATTENTION; ABNORMALITIES AB Objective: To understand the underlying dynamic neurophysiological changes over the course of schizophrenia, it is important to study subjects longitudinally from the early stage of the illness. We previously reported that visual P300 was already impaired in patients with first-episode schizophrenia (FESZ). This study demonstrates how the visual P300, as well as earlier components P1, N1, and N200, changed at the 1-year follow-up after their initial measurement. Methods: Visual ERPs were recorded with the same experimental paradigm and acquisition protocol at both time points in FESZ (n = 18) and healthy comparison subjects (n = 24). Participants silently counted infrequent target stimuli ("x") amid standard stimuli ("y") presented on the screen while the 64-channel electroencephalogram was recorded. Results: FESZ showed smaller visual P300, N200, P1 (trend level) amplitude and delayed P300 and N1 latency at both time points; however, only P300 showed progressive amplitude reduction over the course of the illness at 1-year follow-up. P300 latency did not change over time in either group. FESZ showed significantly reduced Spatial Span total score at both time points, and there was a significant negative correlation between P300 peak amplitude and the Brief Psychiatric Rating Scale positive symptom score at baseline. Conclusion: These data show progressive P300 amplitude reduction in response to visual stimuli in the early stage of schizophrenia. These visual P300 findings support the concept of progression of schizophrenia, suggesting the usefulness of the visual P300 as a biological marker of progression. C1 [Oribe, Naoya; Hirano, Yoji; del Re, Elisabetta; McCarley, Robert W.; Niznikiewicz, Margaret] Harvard Univ, Sch Med, Clin Neurosci Div,Dept Psychiat, Lab Neurosci,VA Boston Healthcare Syst Brockton D, Brockton, MA 02301 USA. [Oribe, Naoya; Hirano, Yoji; Spencer, Kevin M.] Harvard Univ, Sch Med, Dept Psychiat,Boston Div, Neural Dynam Lab,Boston Vet Affairs Healthcare Sy, Boston, MA 02115 USA. [Oribe, Naoya; Hirano, Yoji; Kanba, Shigenobu] Kyushu Univ, Grad Sch Med Sci, Dept Neuropsychiat, Fukuoka 812, Japan. [Seidman, Larry; Mesholam-Gately, Raquelle] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr,Publ Psychiat Div,B, Boston, MA 02115 USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp,Connors Ctr Womens Hlth & G, Boston, MA 02115 USA. [Goldstein, Jill M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Shenton, Martha] Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Shenton, Martha] Brigham & Womens Hosp, Dept Radiol, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Shenton, Martha] Harvard Univ, Sch Med, Boston Div, Res & Dev,Boston Vet Affairs Healthcare Syst, Boston, MA USA. RP Niznikiewicz, M (reprint author), Harvard Univ, Sch Med, Dept Psychiat 116A, VA Boston Healthcare Syst,Brockton Div, 940 Belmont St, Brockton, MA 02301 USA. EM Margaret_Niznikiewicz@hms.harvard.edu FU Department of Veterans Affairs Medical Research Awards (Schizophrenia Center, Merit Awards); National Institute of Mental Health [K05MH070047, R01MH50747, R01MH40799, R01MH052807, CIDAR P50MH080272]; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation [S2208]; Japan Society for the Promotion of Science [B 22791129]; Fund for Pharmacopsychiatry Research from SENSHIN Medical Research Foundation FX Department of Veterans Affairs Medical Research Awards (Schizophrenia Center, Merit Awards to R.W.M. and M.E.S.); National Institute of Mental Health (K05MH070047 and R01MH50747 to M.E.S., R01MH40799 and R01MH052807 to R.W.M., CIDAR P50MH080272 to R.W.M. and M.E.S.); Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation (S2208 to S.K.) and Grant-in-Aid for Young Scientists (B 22791129 to Y.H.) from Japan Society for the Promotion of Science; Fund for Pharmacopsychiatry Research (to Y.H.) from SENSHIN Medical Research Foundation. NR 74 TC 1 Z9 1 U1 2 U2 8 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 MAR PY 2015 VL 41 IS 2 BP 460 EP 470 DI 10.1093/schbul/sbu083 PG 11 WC Psychiatry SC Psychiatry GA CD3LI UT WOS:000350979500021 PM 24914176 ER PT J AU Song, YS Blackwell, T Yaffe, K Ancoli-Israel, S Redline, S Stone, KL AF Song, Yeonsu Blackwell, Terri Yaffe, Kristine Ancoli-Israel, Sonia Redline, Susan Stone, Katie L. CA Osteoporotic Fractures Men MrOS S TI Relationships Between Sleep Stages and Changes in Cognitive Function in Older Men: The MrOS Sleep Study SO SLEEP LA English DT Article DE aging; cognitive function; cohort study; sleep stages ID SLOW-WAVE SLEEP; CARDIOVASCULAR HEALTH COGNITION; VISUAL-DISCRIMINATION TASK; EYE-MOVEMENT SLEEP; OSTEOPOROTIC FRACTURES; ALZHEIMERS-DISEASE; DEMENTIA; ADULTS; PERFORMANCE; POPULATION AB Study Objective: To investigate the associations between sleep stage distributions and subsequent decline in cognitive function in older men over time. Design: A population-based prospective substudy of the Osteoporotic Fractures in Men Study. Settings: Six sites in the United States. Participants: Community-dwelling men aged 67 y or older (n = 2,601), who were free of probable dementia at sleep visit. Follow-up averaged 3.4 y. Measurement and Results: Sleep stages were identified by in-home polysomnography at the initial sleep visit (2003-2005). Cognitive outcomes were assessed with the Trail Making Test Part B and Modified Mini-Mental State Examination (3MS) at sleep visit and two follow-up visits. After adjusting for multiple confounders compared with men in the lowest quartile of percent of sleep time spent in Stage N1, those in the highest quartile had a twofold increase in cognitive decline for both cognitive tests (adjusted annualized percent change/y: Trail Making Test Part B Q1 = 1.06, Q4 = 2.45, P = 0.01; 3MS Q1 = -0.27, Q4 = -0.48, P = 0.03). In addition, compared with men in the highest quartile, men in the lowest quartile of percent of sleep time in Stage R revealed more cognitive decline on the 3MS (adjusted annualized percent change/y: Q1 = -0.49, Q4 = -0.22, P = 0.003). These findings were consistent even after further adjustment of total sleep time and sleep disordered breathing. No significant relationships between other sleep stages (N2, N3) and cognitive change were found. Conclusion: Increased time in Stage N1 sleep and less time in Stage REM sleep are associated with worsening cognitive performance in older men over time. C1 [Song, Yeonsu] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Blackwell, Terri; Stone, Katie L.] San Francisco Coordinating Ctr, San Francisco, CA 94107 USA. [Blackwell, Terri; Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Psychiat Neurol & Epidemiol, San Francisco, CA 94143 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA. [Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Stone, KL (reprint author), San Francisco Coordinating Ctr, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM kstone@sfcc-cpmc.net FU National Institutes of Health; National Institute on Aging (NIA); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Advancing Translational Sciences (NCATS); NIH Roadmap for Medical Research [U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1 TR000128]; National Heart, Lung, and Blood Institute [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, R01 HL070839]; ResMed Foundation; NIH FX This was not an industry supported study. The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. The National Heart, Lung, and Blood Institute provides funding for the ancillary MrOS Sleep Study, "Outcomes of Sleep Disorders in Older Men," under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839. The analysis was performed at California Pacific Medical Center Research Institute, San Francisco, CA. Dr. Ancoli-Israel is a consultant and on the scientific advisory board for Arena, Ferring Pharmaceuticals Inc., Jansen, Merck, NeuroVigil, Inc., and Purdue Pharma LP. Dr. Redline received research grants from ResMed Foundation and equipment for use in research from ResMed Inc and Philips-Respironics. Dr. Yaffe serves on data safety monitoring boards for Takeda Pharmaceuticals, Inc. and an NIH sponsored study. She is a consultant for Novartis and Pfizer and serves on the Beeson Scientific Advisory Board. The other authors have indicated no financial conflicts of interest. NR 71 TC 8 Z9 8 U1 6 U2 13 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 MAR PY 2015 VL 38 IS 3 BP 411 EP 421 DI 10.5665/sleep.4500 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CC8WE UT WOS:000350648500012 PM 25325465 ER PT J AU Jakobiec, FA Callahan, AB Stagner, AM Lee, NG Rashid, A Mendoza, P Grove, A Freitag, SK AF Jakobiec, Frederick A. Callahan, Alison B. Stagner, Anna M. Lee, N. Grace Rashid, Alia Mendoza, Pia Grove, Arthur Freitag, Suzanne K. TI Malignant rhabdoid transformation of a longstanding, aggressive, and recurrent orbital angiomyxoma SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE orbit; angiomyxoma; rhabdoid tumor; vimentin; cytokeratin; INI1 ID INFLAMMATORY MYOFIBROBLASTIC TUMOR; ATYPICAL TERATOID/RHABDOID TUMOR; LACRIMAL GLAND; SOFT-TISSUE; IMMUNOHISTOCHEMICAL ANALYSIS; EPITHELIOID SARCOMA; MULTIMODAL THERAPY; CELL-CARCINOMA; FEATURES; MYOEPITHELIOMA AB A 47-year-old woman presented with a medial orbital tumor initially diagnosed as either a myxoid neurofibroma or myoepithelioma. Over 30 years the tumor recurred seven times and was serially debulked. Careful histopathologic analysis. coupled with immunohistochemical studies performed on the last two biopsies established the rare diagnosis of a locally aggressive angiomyxoma (because of its local infiltrative growth) with myofibroblastic features (smooth muscle actin and calponin positivity and desmin negativity). The last recurrence manifested at a shorter interval than the earlier ones, suggesting an accelerating clinical course. By this late stage there was complete blindness, a frozen globe, and extreme, unmeasurable proptosis accompanied by massive chemosis and eyelid fullness. An exenteration was performed, and the orbital contents contained a persistent angiomyxoma, but additionally, another cellular population had emerged-mitotically active cells with a malignant rhabdoid phenotype (round shape, cytoplasmic hyaline/globoid inclusions composed of whorls of compact vimentin filaments as well as epithelial membrane antigen and focal cytokeratin positivity). This is the first orbital case of a rhabdoid transformation of a benign orbital mesenchymal tumor:Shortly after the exenteration, multifocal metastases, notably to the lungs, were found, leading to the introduction of chemotherapy, which was discontinued because of non-responsiveness of the tumor and patient intolerance. After 1 year of follow up, the patient is still alive, but has persistent active disease with widespread metastases and a guarded prognosis. (C) 2015 Elsevier Inc. All rights reserved. C1 [Jakobiec, Frederick A.; Callahan, Alison B.; Stagner, Anna M.; Lee, N. Grace; Rashid, Alia; Mendoza, Pia; Grove, Arthur; Freitag, Suzanne K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jakobiec, Frederick A.; Stagner, Anna M.; Rashid, Alia; Mendoza, Pia] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Dept Ophthalmol, Boston, MA 02114 USA. [Lee, N. Grace; Freitag, Suzanne K.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol Ophthalm Plast Surg Serv, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St Suite 327, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 72 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 0039-6257 EI 1879-3304 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAR-APR PY 2015 VL 60 IS 2 BP 166 EP 176 DI 10.1016/j.survophthal.2014.12.002 PG 11 WC Ophthalmology SC Ophthalmology GA CC7HX UT WOS:000350539400007 PM 25595060 ER PT J AU Mayers, JR Vander Heiden, MG AF Mayers, Jared R. Vander Heiden, Matthew G. TI Famine versus feast: understanding the metabolism of tumors in vivo SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review DE cancer metabolism; tumor metabolism; cell proliferation; nutrient availability ID CANCER-ASSOCIATED FIBROBLASTS; AMINO-ACID-CONCENTRATIONS; IMAGING MASS-SPECTROMETRY; RAS-TRANSFORMED CELLS; PANCREATIC-CANCER; GLUTAMINE-METABOLISM; AEROBIC GLYCOLYSIS; C-MYC; GASTROINTESTINAL CANCER; ALPHA-KETOGLUTARATE AB To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo. Whole-body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo. C1 [Mayers, Jared R.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Mayers, Jared R.; Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Vander Heiden, Matthew G.] Harvard Univ, Sch Med, Boston, MA USA. [Vander Heiden, Matthew G.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA. RP Vander Heiden, MG (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mvh@mit.edu OI Mayers, Jared/0000-0002-8607-1787 FU Burroughs Wellcome Fund; Lustgarten Foundation; American Association for Cancer Research; National Cancer Institute; [F30 CA183474] FX We thank all members of the laboratory of M.G.V.H. for their thoughtful discussion and feedback throughout the course of developing this manuscript, and specifically thank A.M. Hosios and D.Y. Gui for assistance with generating the model of proliferation in culture, and S.M. Davidson for discussions regarding metabolism in vivo. We thank R.J. Deberardinis, A.M. Hosios, and W.J. Israelsen for input into compiling nutrient values in plasma We also thank the reviewers for their time and thoughtful critiques to improve our manuscript. Owing to space limitations we regret being unable to cite many excellent papers. J.R.M. was supported by F30 CA183474. M.G.V.H. acknowledges support from the Burroughs Wellcome Fund, the Lustgarten Foundation, the American Association for Cancer Research, and the National Cancer Institute. NR 114 TC 27 Z9 27 U1 3 U2 23 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAR PY 2015 VL 40 IS 3 BP 130 EP 140 DI 10.1016/j.tibs.2015.01.004 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC8IT UT WOS:000350612400002 PM 25639751 ER PT J AU Fujioka, M Okano, H Edge, ASB AF Fujioka, Masato Okano, Hideyuki Edge, Albert S. B. TI Manipulating cell fate in the cochlea: a feasible therapy for hearing loss SO TRENDS IN NEUROSCIENCES LA English DT Review DE sensory systems; cell replacement; hearing loss; hair cells ID MAMMALIAN INNER-EAR; HAIR-CELLS; STEM-CELLS; ACOUSTIC TRAUMA; MOUSE COCHLEA; IN-VIVO; REGULATES DEVELOPMENT; SUPPORTING CELLS; REGENERATION; EXPRESSION AB Mammalian auditory hair cells do not spontaneously regenerate, unlike hair cells in lower vertebrates, including fish and birds. In mammals, hearing loss due to the loss of hair cells is permanent and intractable. Recent studies in the mouse have demonstrated spontaneous hair cell regeneration during a short postnatal period, but this regenerative capacity is lost in the adult cochlea. Reduced regeneration coincides with a transition that results in a decreased pool of progenitor cells in the cochlear sensory epithelium. Here, we review the signaling cascades involved in hair cell formation and morphogenesis of the organ of Corti in developing mammals, the changing status of progenitor cells in the cochlea, and the regeneration of auditory hair cells in adult mammals. C1 [Fujioka, Masato] Keio Univ, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Tokyo, Japan. [Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Tokyo 160, Japan. [Edge, Albert S. B.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, Boston, MA 02114 USA. [Edge, Albert S. B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Edge, ASB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM albert_edge@meei.harvard.edu RI Hidokano, Hideyuki/J-5973-2013 FU MEXT [24592560]; MHLW (Comprehensive Research on Disability Health and Welfare); Takeda Science Foundation; NIH [RO1 DC007174, R21 DC010440, P30 DC05209] FX We are grateful to T. Nagai for his excellent technical assistance in the electron microscopy. This work was supported by MEXT. KAKENHI (Grant-in-Aid for Scientific Research (C), 24592560), by MHLW (Comprehensive Research on Disability Health and Welfare), by Takeda Science Foundation to M.F, and by NIH grants RO1 DC007174, R21 DC010440, and P30 DC05209. NR 39 TC 5 Z9 5 U1 0 U2 10 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 2015 VL 38 IS 3 BP 139 EP 144 DI 10.1016/j.tins.2014.12.004 PG 6 WC Neurosciences SC Neurosciences & Neurology GA CD2UA UT WOS:000350933300003 PM 25593106 ER PT J AU Shan, L Bao, AM Swaab, DF AF Shan, Ling Bao, Ai-Min Swaab, Dick F. TI The human histaminergic system in neuropsychiatric disorders SO TRENDS IN NEUROSCIENCES LA English DT Review DE histamine; Parkinson's disease; Alzheimer's disease; Huntington's disease; narcolepsy; Tourette's syndrome ID MELANIN-CONCENTRATING HORMONE; CEREBROSPINAL-FLUID HISTAMINE; RECEPTOR-MEDIATED INHIBITION; L-HISTIDINE DECARBOXYLASE; ALZHEIMERS-DISEASE BRAIN; PARKINSONS-DISEASE; H-3 RECEPTOR; HUMAN HYPOTHALAMUS; TUBEROMAMMILLARY NUCLEUS; INVERSE AGONIST AB Histaminergic neurons are exclusively located in the hypothalamic tuberomamillary nucleus, from where they project to many brain areas. The histaminergic system is involved in basic physiological functions, such as the sleep-wake cycle, energy and endocrine homeostasis, sensory and motor functions, cognition, and attention, which are all severely affected in neuropsychiatric disorders. Here, we present recent postmortem findings on the alterations in this system in neuropsychiatric disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), depression, and narcolepsy. In addition, we highlight the need to validate animal models for these diseases and also for burette's syndrome (TS) in relation to alterations in the histaminergic system. Moreover, we discuss the potential for, and concerns over, the use of novel histamine 3 receptor (H3R) antagonists/inverse agonists as treatment for such disorders. C1 [Shan, Ling; Bao, Ai-Min] Zhejiang Univ, Dept Neurobiol, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China. [Shan, Ling; Swaab, Dick F.] Netherlands Inst Neurosci, NL-1105 BA Amsterdam, Netherlands. [Shan, Ling] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Shan, Ling] Vet Adm Greater Los Angeles Hlth Care Syst, Neurobiol Res, North Hills, CA 91343 USA. RP Bao, AM (reprint author), Zhejiang Univ, Dept Neurobiol, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China. EM baoaimin@zju.edu.cn OI Shan, Ling/0000-0002-4765-2474 FU Program of Introducing Talents of Discipline to Universities of China [B13026]; Zhejiang University K.P. Chao's Hi-Tech Foundation for Scholars and Scientists; China Scholarship Council [30201]; European Histamine Research Society; NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation FX This work was supported by the Program of Introducing Talents of Discipline to Universities of China (Nr. B13026) to D.S. and A-M.B., and supported by Zhejiang University K.P. Chao's Hi-Tech Foundation for Scholars and Scientists to D.S. It was also supported by the China Scholarship Council for State Scholarship Fund [grant number (2007) 30201 to L.S. The work has been presented and awarded a Young Investigators Award by the European Histamine Research Society to L.S. L.S. is currently supported by a (2014) NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. The authors also thank The Netherlands Brain Bank (Director Inge Huitinga) for providing human brain material and clinical data, and W.T.P. Verweij for secretarial assistance, NR 112 TC 22 Z9 23 U1 4 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 2015 VL 38 IS 3 BP 167 EP 177 DI 10.1016/j.tins.2014.12.008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CD2UA UT WOS:000350933300006 PM 25575625 ER PT J AU Shamitoff, A Lamba, R Bennett, GL Catanzano, T Moshiri, M Katz, DS Bhargava, P AF Shamitoff, Anna Lamba, Ramit Bennett, Genevieve L. Catanzano, Tara Moshiri, Mariam Katz, Douglas S. Bhargava, Puneet TI Practice Patterns in Imaging of the Abdomen and Pelvis of the Pregnant Patient A Survey from the 2012 Radiological Society of North America Annual Meeting Controversies Session SO ULTRASOUND QUARTERLY LA English DT Editorial Material ID ABDOMINAL-PAIN; UROLITHIASIS; COMPLICATIONS; MANAGEMENT; DIAGNOSIS C1 [Shamitoff, Anna; Moshiri, Mariam; Bhargava, Puneet] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Lamba, Ramit] Univ Calif, Dept Radiol, Sacramento, CA USA. [Bennett, Genevieve L.] NYU, Dept Radiol, Langone Med Ctr, New York, NY 10016 USA. [Bennett, Genevieve L.] Sch Med, New York, NY USA. [Catanzano, Tara] Baystate Med Ctr, Dept Radiol, Springfield, MA USA. [Katz, Douglas S.] Winthrop Univ Hosp, Dept Radiol, Mineola, NY 11501 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA 98108 USA. RP Bhargava, P (reprint author), VA Puget Sound Hlth Care Syst, Dept Radiol, 1660 S ColumbianWay, Seattle, WA 98108 USA. EM bhargp@uw.edu NR 15 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-8771 EI 1536-0253 J9 ULTRASOUND Q JI Ultrasound Q. PD MAR PY 2015 VL 31 IS 1 BP 2 EP 4 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CC3XO UT WOS:000350284800002 PM 25706359 ER PT J AU Wall, DJ Javitt, MC Glanc, P Bhosale, PR Harisinghani, MG Harris, RD Khati, NJ Mitchell, DG Nyberg, DA Pandharipande, PV Pannu, HK Shipp, TD Siegel, CL Simpson, L Wong-You-Cheong, JJ Zelop, CM AF Wall, Darci J. Javitt, Marcia C. Glanc, Phyllis Bhosale, Priyadarshani R. Harisinghani, Mukesh G. Harris, Robert D. Khati, Nadia J. Mitchell, Donald G. Nyberg, David A. Pandharipande, Pari V. Pannu, Harpreet K. Shipp, Thomas D. Siegel, Cary Lynn Simpson, Lynn Wong-You-Cheong, Jade J. Zelop, Carolyn M. TI ACR Appropriateness Criteria (R) Infertility SO ULTRASOUND QUARTERLY LA English DT Article DE Appropriateness Criteria; infertility; ultrasound; MRI; hysterosalpingogram; saline infusion sonohysterography ID MULLERIAN DUCT ANOMALIES; POLYCYSTIC-OVARY-SYNDROME; CURRENT-DURATION APPROACH; DE-SAC OBLITERATION; PELVIC ENDOMETRIOSIS; FEMALE INFERTILITY; UTERINE ANOMALIES; 3-DIMENSIONAL ULTRASONOGRAPHY; TRANSVAGINAL SONOGRAPHY; INTRAUTERINE ABNORMALITIES AB Appropriate imaging for women undergoing infertility workup depends upon the clinician's suspicion for potential causes of infertility. Transvaginal US is the preferred modality to assess the ovaries for features of polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility. For women who have a history or clinical suspicion of endometriosis, which affects at least one third of women with infertility, both MRI and pelvic US can provide valuable information. If tubal occlusion is suspected, whether due to endometriosis, previous pelvic inflammatory disease, or other cause, hysterosalpingogram (HSG) is the preferred method of evaluation. To assess for anatomic causes of recurrent pregnancy loss (RPL) such as Mullerian anomalies, synechiae, and leiomyomas, saline infusion sonohysterography, MRI and 3-D US are most appropriate. Up to 10% of women suffering recurrent pregnancy loss have a congenital Mullerian anomaly. When assessment of the pituitary gland is indicated, MRI is the imaging exam of choice. The American College of Radiology Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Wall, Darci J.] Mayo Clin, Rochester, MN 55902 USA. [Javitt, Marcia C.] Rambam Healthcare Campus, Haifa, Israel. [Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Bhosale, Priyadarshani R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Harisinghani, Mukesh G.; Pandharipande, Pari V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Robert D.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Khati, Nadia J.] George Washington Univ Hosp, Washington, DC USA. [Mitchell, Donald G.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Nyberg, David A.] Old Vicarage, Worcester Pk, Worcs, England. [Pannu, Harpreet K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shipp, Thomas D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shipp, Thomas D.; Simpson, Lynn; Zelop, Carolyn M.] Amer Coll Obstetricians & Gynecologists, Washington, DC USA. [Siegel, Cary Lynn] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Simpson, Lynn] Columbia Univ, New York, NY USA. [Wong-You-Cheong, Jade J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Zelop, Carolyn M.] Valley Hosp, Ridgewood, NJ USA. RP Wall, DJ (reprint author), Mayo Clin, Rochester, MN 55902 USA. EM wall.darci@mayo.edu NR 102 TC 1 Z9 1 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-8771 EI 1536-0253 J9 ULTRASOUND Q JI Ultrasound Q. PD MAR PY 2015 VL 31 IS 1 BP 37 EP 44 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CC3XO UT WOS:000350284800007 PM 25706363 ER PT J AU Slade, EP Goldman, HH AF Slade, Eric P. Goldman, Howard H. TI The Dynamics of Psychiatric Bed Use in General Hospitals SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Psychiatric inpatient care; Scatter beds; Length-of-stay ID EMERGENCY-DEPARTMENT; CARE AB This study examines general hospitals' adjustments in psychiatric bed utilization practices in response to increases in psychiatric inpatient admissions. Using panel data from 439 hospitals, monthly observations (N = 7,831) between 2007 and 2010 on psychiatric admissions, psychiatric bed occupancy rates, and average length-of-stay were created for psychiatric inpatients. In fixed-effects regressions, an increase in psychiatric admissions was associated with an increase in the probability of psychiatric bed use exceeding 100 % occupancy and with a reduction of mean length-of-stay. These results were confirmed in instrumental variables models. General hospitals may dynamically adjust bed utilization practices in response to changing psychiatric bed needs. An implication of this dynamic adjustment model is that bed shortages are likely to be local, transitory events. C1 [Slade, Eric P.] US Dept Vet Affairs, VA Capitol Healthcare Network Mental Illness Res, Baltimore, MD 21201 USA. [Slade, Eric P.; Goldman, Howard H.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21227 USA. RP Slade, EP (reprint author), US Dept Vet Affairs, VA Capitol Healthcare Network Mental Illness Res, 10 N Greene St, Baltimore, MD 21201 USA. EM eslade@psych.umaryland.edu; hh.goldman@verizon.net FU NIMH NIH HHS [R21 MH096285] NR 18 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD MAR PY 2015 VL 42 IS 2 BP 139 EP 146 DI 10.1007/s10488-014-0554-4 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CC4DR UT WOS:000350301500003 PM 24756929 ER PT J AU Gumaste, P Ortiz, AE Patel, A Baron, J Harris, R Barr, R AF Gumaste, Priyanka Ortiz, Arisa E. Patel, Amit Baron, Jonathan Harris, Ronald Barr, Ronald TI Generalized Basaloid Follicular Hamartoma Syndrome: A Case Report and Review of the Literature SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article; Proceedings Paper CT CalDerm-Society Annual Meeting CY SEP 20-22, 2013 CL Santa Barbara, CA SP CalDerm Soc DE basaloid follicular hamartoma ID CELL CARCINOMA; MYASTHENIA-GRAVIS; FIBROEPITHELIOMA; EXPRESSION; ALOPECIA; THERAPY; DISEASE; PINKUS AB Basaloid follicular hamartoma (BFH) is a rare, generally benign lesion of importance because of its clinical and histopathological similarity to infundibulocystic basal cell carcinoma. Autosomal dominant generalized BFH syndrome is 1 of the 5 clinical forms of BFH that has been described in the literature. We report a case of BFH syndrome in a 47-year-old Hispanic female who presented with an increasing number of small 1- to 2-mm tan to brown smooth facial papules, few palmar pits, and cobblestoning of the tongue. Her mother had similar lesions on her face. A biopsy of one of the patient's facial lesions confirmed the diagnosis of BFH. Of note, this patient later presented with rapid growth of one of her facial lesions, and a subsequent biopsy confirmed the development of a basal cell carcinoma arising within one of her BFH lesions. Although BFH is classically stable for years and does not require immediate surgical removal, our case highlights the importance of continual monitoring of these patients, given the potential for malignant transformation of these lesions. C1 [Gumaste, Priyanka] Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Ortiz, Arisa E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatol Cosmet & Laser Ctr,Dept Dermatol, Boston, MA 02115 USA. [Ortiz, Arisa E.] Univ Calif San Diego, Div Dermatol, Dept Med, San Diego, CA 92122 USA. [Patel, Amit; Harris, Ronald] UC Irvine, Dept Dermatol, Irvine, CA USA. [Baron, Jonathan] RBGB Dermatol, Santa Ana, CA USA. [Barr, Ronald] Laguna Pathol Med Grp, Laguna Beach, CA USA. RP Ortiz, AE (reprint author), Univ Calif San Diego, 8899 Univ Ctr Lane 350, San Diego, CA 92122 USA. EM arisaortiz@gmail.com NR 21 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0193-1091 EI 1533-0311 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD MAR PY 2015 VL 37 IS 3 BP E37 EP E40 PG 4 WC Dermatology SC Dermatology GA CC4AW UT WOS:000350294000003 PM 24698936 ER PT J AU Maria, MMMS Baker, NL Ramakrishnan, V Brady, KT McRae-Clark, A AF Maria, Megan M. Moran-Santa Baker, Nathaniel L. Ramakrishnan, Viswanathan Brady, Kathleen T. McRae-Clark, Aimee TI Impact of acute guanfacine administration on stress and cue reactivity in cocaine-dependent individuals SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Cocaine; cocaine cues; guanfacine; stress ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; ALPHA-2-ADRENERGIC RECEPTOR AGONISTS; ANXIOGENIC DRUG YOHIMBINE; GENDER-DIFFERENCES; INDUCED REINSTATEMENT; DSM-IV; SEEKING; CLONIDINE; RATS; WITHDRAWAL AB Background: Stress and drug-paired cues increase drug craving and noradrenergic activity in cocaine-dependent individuals. Thus, medications that attenuate noradrenergic activity may be effective therapeutic treatment options for cocaine-dependent individuals. Objectives: To examine the impact of acute administration of the alpha 2 adrenergic receptor agonist guanfacine on responses to multiple risk factors for relapse in cocaine-dependent individuals. Methods: In a double-blind, placebo-controlled study, cocaine-dependent individuals (n = 84), were randomized to receive either 2 mg guanfacine (n = 50) or placebo (n = 34). Within each treatment arm, subjects were randomized to either a stress (guanfacine n = 26; placebo n = 15) or a no-stress (guanfacine n = 24; placebo n = 19) group. Participants in the stress group performed the Trier Social Stress Test. Subjects in each group were exposed to a neutral cue and then to cocaine-related cues. Plasma cortisol and subjective responses were compared between the four groups. Results: The no-stress guanfacine group reported greater craving in response to cocaine cues as compared to the neutral cue (p<0.001). The guanfacine stress group reported greater subjective stress at the neutral cue than at baseline (p = 0.032). The cocaine cue increased subjective stress in the guanfacine (p<0.001) no-stress group. There were no effects of guanfacine on cortisol levels in either the stress or no stress groups (all >40.70). Conclusion: This study found no effects of a single 2mg dose of guanfacine on reactivity to stress and cues alone or on the interaction of stress and drug cues. In cocaine-dependent individuals an acute 2mg dose of guanfacine may not be an effective therapeutic treatment strategy. C1 [Maria, Megan M. Moran-Santa; Brady, Kathleen T.; McRae-Clark, Aimee] Med Univ S Carolina, Dept Psychiat & Behav Neurosci, Clin Neurosci Div, Charleston, SC 29425 USA. [Baker, Nathaniel L.; Ramakrishnan, Viswanathan] Med Univ S Carolina, Dept Publ Hlth Sci, Clin Neurosci Div, Charleston, SC 29425 USA. [Brady, Kathleen T.] Ralph H Johnson VAMC, Charleston, SC USA. RP Maria, MMMS (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, 125 Doughty St, Charleston, SC 29425 USA. EM moranm@musc.edu FU National Institutes of Health; National Institute on Drug Abuse [R01DA021690]; National Institute of Child Health and Human Development [K12HD055885]; National Center for Advancing Translational Sciences [UL1TR000062] FX This work was supported by National Institutes of Health; National Institute on Drug Abuse (R01DA021690), National Institute of Child Health and Human Development K12HD055885, National Center for Advancing Translational Sciences (UL1TR000062). NR 44 TC 0 Z9 0 U1 2 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 EI 1097-9891 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD MAR PY 2015 VL 41 IS 2 BP 146 EP 152 DI 10.3109/00952990.2014.945590 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA CC2XW UT WOS:000350209500006 ER PT J AU Ramos, EM Gillis, T Mysore, JS Lee, JM Gogele, M D'Elia, Y Pichler, I Sequeiros, J Pramstaller, PP Gusella, JF MacDonald, ME Alonso, I AF Ramos, Eliana Marisa Gillis, Tammy Mysore, Jayalakshmi S. Lee, Jong-Min Goegele, Martin D'Elia, Yuri Pichler, Irene Sequeiros, Jorge Pramstaller, Peter P. Gusella, James F. MacDonald, Marcy E. Alonso, Isabel TI Haplotype Analysis of the 4p16.3 Region in Portuguese Families With Huntington's Disease SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE Haplotype analysis; Huntington's disease; Instability; Genetic diversity; Delta 2642 allele ID AGE-OF-ONSET; TRINUCLEOTIDE REPEAT; MOLECULAR ANALYSIS; CAG REPEAT; INTERMEDIATE ALLELES; HD GENE; POPULATION; POLYMORPHISM; CHROMOSOMES; INSTABILITY AB Huntington's disease (HD) is a neurodegenerative disorder characterized by involuntary choreic movements, cognitive impairment, and behavioral changes, caused by the expansion of an unstable CAG repeat in HTT. We characterized the genetic diversity of the HD mutation by performing an extensive haplotype analysis of approximate to 1Mb region flanking HTT in over 300 HD families of Portuguese origin. We observed that haplotype A, marked by HTT delta2642, was enriched in HD chromosomes and carried the two largest expansions reported in the Portuguese population. However, the most frequent HD haplotype B carried one of the largest (+12 CAGs) expansions, which resulted in an allele class change to full penetrance. Despite having a normal CAG distribution skewed to the higher end of the range, these two core haplotypes had similar expanded CAG repeat sizes compared to the other major core haplotypes (C and D) and there was no statistical difference in transmitted repeat instability across haplotypes. We observed a diversity of HTT region haplotypes in both normal and expanded chromosomes, representative of more than one ancestral chromosome underlying HD in Portugal, where multiple independent events on distinct chromosome 4 haplotypes have given rise to expansion into the pathogenic range. (c) 2015 Wiley Periodicals, Inc. C1 [Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S.; Lee, Jong-Min; Gusella, James F.; MacDonald, Marcy E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ramos, Eliana Marisa; Sequeiros, Jorge; Alonso, Isabel] Univ Porto, UnIGENe, IBMC Inst Mol & Cell Biol, P-4150180 Oporto, Portugal. [Goegele, Martin; D'Elia, Yuri; Pichler, Irene; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Pramstaller, Peter P.] Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Sequeiros, Jorge; Alonso, Isabel] Univ Porto, CGPP, IBMC Inst Mol & Cell Biol, P-4150180 Oporto, Portugal. [Sequeiros, Jorge; Alonso, Isabel] Univ Porto, ICBAS, P-4150180 Oporto, Portugal. RP Alonso, I (reprint author), Univ Porto, UnIGENe, Rua Campo Alegre 823, P-4150180 Oporto, Portugal. EM ialonso@ibmc.up.pt RI Alonso, Isabel/I-4307-2013 OI Alonso, Isabel/0000-0001-8549-6903 FU NINDS [NS16367, NS32765]; Fundacao para a Ciencia e a Tecnologia [SFRH/BD/44335/2008]; Programa Ciencia, POPH - QREN - Tipologia 4.2 - Promocao do Emprego Cientifico, ESF; MCTES (Ministerio da Ciencia e Ensino Superior); Ministry of Health; Department of Educational Assistance FX Grant sponsor: NINDS; Grant number: NS16367, NS32765; Grant sponsor: Fundacao para a Ciencia e a Tecnologia; Grant number: SFRH/BD/44335/2008; Grant sponsor: Programa Ciencia, POPH - QREN - Tipologia 4.2 - Promocao do Emprego Cientifico, ESF and MCTES (Ministerio da Ciencia e Ensino Superior); Grant sponsor: Ministry of Health and Department of Educational Assistance. NR 32 TC 1 Z9 1 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR PY 2015 VL 168 IS 2 BP 135 EP 143 DI 10.1002/ajmg.b.32289 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA CC0XO UT WOS:000350063400007 PM 25656686 ER PT J AU Neuner, J Fedders, M Caravella, M Bradford, L Schapira, M AF Neuner, Joan Fedders, Megan Caravella, Mary Bradford, Lisa Schapira, Marilyn TI Meaningful Use and the Patient Portal: Patient Enrollment, Use, and Satisfaction With Patient Portals at a Later-Adopting Center SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE meaningful use; electronic health records; patient satisfaction; medical informatics ID MEDICAL-RECORD; HEALTH RECORD; USE CRITERIA; ACCESS; SERVICES; MODEL; WILL; CARE AB Many physicians are adopting patient portals in response to governmental incentives for meaningful use (MU), but the stage 2 requirements for portal use may be particularly challenging for newer electronic health record (EHR) users. This study examined enrollment, use based on MU requirements, and satisfaction in a recently adopting fee-for-service multispecialty system. Between 2010 and 2012, overall portal enrollment increased from 13.2% to 23.1% but varied substantially by physician specialty. In 2013, more than 97% of physicians would have met requirements for a stage 2 MU utilization measure requiring that patients download personal health information, but only 38% of all physicians (87% of primary care physicians [PCPs] and 37% of other specialists) would have met e-mail requirements. Satisfaction with the portal overall and with portal-based e-mails was high. These results suggest that later-adopting PCPs can succeed in providing satisfactory record and e-mail access but specialists may find reaching e-mail thresholds more difficult. C1 [Neuner, Joan; Bradford, Lisa] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Fedders, Megan] Med Coll Wisconsin, Froedtert Hosp, Milwaukee, WI 53226 USA. [Caravella, Mary] Univ Connecticut, Sch Business, Storrs, CT USA. [Schapira, Marilyn] Univ Penn, Perleman Sch Med, Philadelphia, PA 19104 USA. [Schapira, Marilyn] Philadelphia VA Med Ctr, CHERP, Philadelphia, PA USA. RP Neuner, J (reprint author), Med Coll Wisconsin, Ctr Patient Care & Outcomes Res, 8701 Watertown Plank Rd,Suite H3100, Milwaukee, WI 53226 USA. EM jneuner@mcw.edu FU CTSI (Clinical and Translational Science Institute) [5520204]; AHW (Advancing a Healthier Wisconsin) award [9520196]; AHW FX The authors received the following financial support for the research, authorship, and/or publication of this article: CTSI (Clinical and Translational Science Institute) Grant Number: 5520204; and AHW (Advancing a Healthier Wisconsin) award Project Number: 9520196. The CTSI Pilot and Collaborative Clinical and Translational Research Grant is supported by AHW. NR 21 TC 8 Z9 8 U1 4 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAR-APR PY 2015 VL 30 IS 2 BP 105 EP 113 DI 10.1177/1062860614523488 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CC6IE UT WOS:000350467800001 PM 24563085 ER PT J AU Turner, AP Hartoonian, N Maynard, C Leipertz, SL Haselkorn, JK AF Turner, Aaron P. Hartoonian, Narineh Maynard, Charles Leipertz, Steven L. Haselkorn, Jodie K. TI Smoking and Physical Activity: Examining Health Behaviors and 15-Year Mortality Among Individuals With Multiple Sclerosis SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Exercise; Mortality; Multiple sclerosis; Physical activity; Rehabilitation; Smoking ID QUALITY-OF-LIFE; UNITED-STATES; EXERCISE; POPULATION; PREVALENCE; VETERANS; VALIDITY; FITNESS; PEOPLE; RISK AB Objectives: To examine 2 modifiable health behaviors smoking and physical activity and their relationship to mortality among individuals with multiple sclerosis (MS). Design: Secondary analysis of Large Health Survey. Setting: Data were obtained from a linkage of the Veterans Affairs (VA) MS National Data Repository, containing information on service provision to all individuals with MS receiving health services within the U.S. Department of Veterans Affairs; the VA 1999 Large Health Survey, containing information on smoking and physical activity; and the VA Vital Status File. All-cause mortality was examined for the 15-year period from 1999 through 2013. Participants: Participants (N=2994) with MS who completed the Large Health Survey containing information on smoking and physical activity. Interventions: Not applicable. Main Outcome Measure: Survival. Results: There were 1500 deaths (50.1%) during the study period. Cox proportional hazard analyses were conducted to examine the association between smoking and physical activity and 15-year mortality. After adjusting for demographic factors, physical functioning, mental health, and comorbid medical conditions, baseline smoking was associated with greater mortality (hazard ratio [HR.] = 1.38; 95% confidence interval [CI], 1.184-1.60). Higher levels of baseline physical activity were associated with lower mortality (activity 1-2 times/wk: HR=.64; 95% CI,.518-.798; activity >= 3 times/wk: HR=.53; 95% CI, .388.715). Conclusions: Results suggest that modifiable health behaviors represent a promising opportunity for intervention to improve the lives of individuals with MS. (C) 2015 by the American Congress of Rehabilitation Medicine C1 [Turner, Aaron P.; Hartoonian, Narineh; Maynard, Charles; Leipertz, Steven L.; Haselkorn, Jodie K.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Turner, Aaron P.; Hartoonian, Narineh; Leipertz, Steven L.; Haselkorn, Jodie K.] VA Multiple Sclerosis Ctr Excellence West, Seattle, WA USA. [Turner, Aaron P.] VA Ctr Excellence Subst Abuse Treatment & Ed, Seattle, WA USA. [Turner, Aaron P.; Hartoonian, Narineh; Haselkorn, Jodie K.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@med.va.gov RI Maynard, Charles/N-3906-2015; OI Maynard, Charles/0000-0002-1644-7814; Turner, Aaron/0000-0001-6897-8003 FU Veterans Affairs (VA) Rehabilitation Research and Development Service Career Development Award [B33I9VA]; VA Center of Excellence in Substance Abuse Treatment and Education; VA Multiple Sclerosis Center of Excellence West; VA Office of Quality and Performance; National Multiple Sclerosis Society [MB0026] FX Supported by a Veterans Affairs (VA) Rehabilitation Research and Development Service Career Development Award (grant no. B33I9VA), the VA Center of Excellence in Substance Abuse Treatment and Education, the VA Multiple Sclerosis Center of Excellence West, VA Office of Quality and Performance, and National Multiple Sclerosis Society (grant no. MB0026). NR 35 TC 5 Z9 5 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2015 VL 96 IS 3 BP 402 EP 409 DI 10.1016/j.apmr.2014.10.014 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CC3QZ UT WOS:000350265400004 PM 25448246 ER PT J AU Carreras, ET Mega, JL AF Carreras, Edward T. Mega, Jessica L. TI Role of Oral Anticoagulants in Patients After an Acute Coronary Syndrome SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE acute coronary syndrome; anticoagulation; non-vitamin K dependent oral anticoagulants ID ELEVATION MYOCARDIAL-INFARCTION; ASSOCIATION TASK-FORCE; ATRIAL-FIBRILLATION; ANTIPLATELET THERAPY; PRACTICE GUIDELINES; WARFARIN; RIVAROXABAN; METAANALYSIS; CLOPIDOGREL; APIXABAN AB After an acute coronary syndrome, patients continue to be at risk of adverse cardiovascular events despite treatment with the current standard of antithrombotic therapy. The risk may be in part secondary to thrombin, which remains elevated after an acute coronary syndrome event. Several studies have investigated the utility of adding oral anticoagulation to post-acute coronary syndrome medical regimens, with the most promising results coming from the addition of low-dose oral direct anticoagulants. Focusing on optimal dosing strategies and applying therapies to the appropriate populations provide the ability to maximize benefit and minimize risk. C1 [Mega, Jessica L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. [Carreras, Edward T.; Mega, Jessica L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Mega, JL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jmega@partners.org FU Johnson Johnson; Bayer; Daiichi Sankyo; AstraZeneca; Eli Lilly; Bristol-Myers Squibb; Sanofi-Aventis; Accumetrics; Nanosphere FX Dr Mega has received research funding from Johnson & Johnson, Bayer, Daiichi Sankyo, AstraZeneca, Eli Lilly, Bristol-Myers Squibb, Sanofi-Aventis, Accumetrics, and Nanosphere, and honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and Portola. Dr Carreras reports no conflicts. NR 24 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 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2015 VL 35 IS 3 BP 520 EP 524 DI 10.1161/ATVBAHA.114.303401 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CC5JV UT WOS:000350395800010 PM 25614282 ER PT J AU Evans, WS Caplan, D Ostrowski, A Michaud, J Guarino, AJ Waters, G AF Evans, William S. Caplan, David Ostrowski, Adam Michaud, Jennifer Guarino, Anthony J. Waters, Gloria TI Working Memory and the Revision of Syntactic and Discourse Ambiguities SO CANADIAN JOURNAL OF EXPERIMENTAL PSYCHOLOGY-REVUE CANADIENNE DE PSYCHOLOGIE EXPERIMENTALE LA English DT Article DE short-term memory; working memory; age; speed of processing; sentence and discourse comprehension ID SHORT-TERM-MEMORY; IMMEDIATE SERIAL-RECALL; GARDEN-PATH SENTENCES; ADULT AGE-DIFFERENCES; INDIVIDUAL-DIFFERENCES; EYE-MOVEMENTS; WORD-LENGTH; LANGUAGE COMPREHENSION; IRRELEVANT SPEECH; RELATIVE CLAUSES AB Two hundred participants, 50 in each of 4 age ranges (19-29 years, 30-49 years, 50-69 years, 70-90 years) were tested for short-term working memory, speed of processing, and online processing of 3 types of sentences in which an initially assigned syntactic structure and/or semantic interpretation had to be revised. Self-paced reading times were longer for the segments that signaled the need for revision; there also were interactions of age and sentence type and speed of processing and sentence type, but not of working memory and sentence type on reading times for these segments. The results provide evidence that working memory does not support the processes that revise the structure and interpretation of sentences and discourse. C1 [Evans, William S.; Ostrowski, Adam; Waters, Gloria] Boston Univ, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. [Caplan, David; Michaud, Jennifer] Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. [Guarino, Anthony J.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Caplan, D (reprint author), Neuropsychol Lab, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIH [AG09661] FX This research was supported by NIH Grant AG09661 to David Caplan and Gloria Waters. NR 106 TC 2 Z9 2 U1 5 U2 13 PU CANADIAN PSYCHOLOGICAL ASSOC PI OTTAWA PA 141 LAURIER AVE WEST, STE 702, OTTAWA, ONTARIO K1P 5J3, CANADA SN 1196-1961 EI 1878-7290 J9 CAN J EXP PSYCHOL JI Can. J. Exp. Psychol.-Rev. Can. Psychol. Exp. PD MAR PY 2015 VL 69 IS 1 SI SI BP 136 EP 155 DI 10.1037/cep0000037 PG 20 WC Psychology, Experimental SC Psychology GA CC7OH UT WOS:000350557300013 PM 25485458 ER PT J AU Surmann, EM Voigt, AY Michel, S Bauer, K Reuschenbach, M Ferrone, S Doeberitz, MV Kloor, M AF Surmann, Eva-Maria Voigt, Anita Y. Michel, Sara Bauer, Kathrin Reuschenbach, Miriam Ferrone, Soldano Doeberitz, Magnus von Knebel Kloor, Matthias TI Association of high CD4-positive T cell infiltration with mutations in HLA class II-regulatory genes in microsatellite-unstable colorectal cancer SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Colorectal cancer; HLA class II antigens; Immune evasion; Microsatellite instability; Tumor-infiltrating lymphocytes ID TUMOR-SPECIFIC ANTIGENS; DR EXPRESSION; ESTABLISHED MELANOMA; INSTABILITY; CARCINOMAS; LYMPHOCYTES; METASTASES; ANTIBODIES; PROGNOSIS; MECHANISM AB Besides being expressed on professional antigen-presenting cells, HLA class II antigens are expressed on various tumors of non-lymphoid origin, including a subset of colorectal cancers (CRC). Information about the regulation of HLA class II antigen expression is important for a better understanding of their role in the interactions between tumor and immune cells. Whether lack of HLA class II antigen expression in tumors reflects the selective immune destruction of HLA class II antigen-expressing tumor cells is unknown. To address this question, we tested whether lack of HLA class II antigen expression in CRC was associated with immune cell infiltration. We selected microsatellite-unstable (MSI-H) CRC, because they show pronounced tumor antigen-specific immune responses and, in a subset of tumors, lack of HLA class II antigen expression due to mutations inactivating HLA class II-regulatory genes. We examined HLA class II antigen expression, mutations in regulatory genes, and CD4-positive T cell infiltration in 69 MSI-H CRC lesions. Mutations in RFX5, CIITA, and RFXAP were found in 13 (28.9 %), 3 (6.7 %), and 1 (2.2 %) out of 45 HLA class II antigen-negative tumors. CD4-positive tumor-infiltrating lymphocyte counts were significantly higher in HLA class II antigen-negative tumors harboring mutations in HLA class II-regulatory genes (107.4 T cells per 0.25 mm(2)) compared to tumors without mutations (55.5 T cells per 0.25 mm(2), p = 0.008). Our results suggest that the outgrowth of tumor cells lacking HLA class II antigen expression due to mutations of regulatory genes is favored in an environment of dense CD4-positive T cell infiltration. C1 [Surmann, Eva-Maria; Voigt, Anita Y.; Michel, Sara; Bauer, Kathrin; Reuschenbach, Miriam; Doeberitz, Magnus von Knebel; Kloor, Matthias] Univ Heidelberg Hosp, Inst Pathol, Dept Appl Tumor Biol, Heidelberg, Germany. [Surmann, Eva-Maria; Voigt, Anita Y.; Michel, Sara; Bauer, Kathrin; Reuschenbach, Miriam; Doeberitz, Magnus von Knebel; Kloor, Matthias] DKFZ German Canc Res Ctr, Clin Cooperat Unit Appl Tumor Biol, Heidelberg, Germany. [Surmann, Eva-Maria; Voigt, Anita Y.; Michel, Sara; Bauer, Kathrin; Reuschenbach, Miriam; Doeberitz, Magnus von Knebel; Kloor, Matthias] Univ Heidelberg Hosp, Mol Med Partnership Unit, Heidelberg, Germany. [Surmann, Eva-Maria; Voigt, Anita Y.; Michel, Sara; Bauer, Kathrin; Reuschenbach, Miriam; Doeberitz, Magnus von Knebel; Kloor, Matthias] European Mol Biol Lab, D-69012 Heidelberg, Germany. [Voigt, Anita Y.] European Mol Biol Lab, Struct & Computat Biol Unit, D-69012 Heidelberg, Germany. [Ferrone, Soldano] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kloor, M (reprint author), Univ Heidelberg Hosp, Inst Pathol, Dept Appl Tumor Biol, Heidelberg, Germany. EM anita.voigt@embl.de; matthias.kloor@med.uni-heidelberg.de RI von Knebel Doeberitz, Magnus/D-2372-2016 OI von Knebel Doeberitz, Magnus/0000-0002-0498-6781 FU Public Health Service (PHS) [R01 CA110249, R01 CA138188]; Deutsche Forschungsgemeinschaft (German Research Foundation); National Cancer Institute FX We are grateful to Nina Nelius, Beate Kuchenbuch and Petra Hofler for the excellent technical support they provided. This work was supported by the Public Health Service (PHS) Grants R01 CA110249 and R01 CA138188 (Soldano Ferrone), awarded by the National Cancer Institute and by a Grant of the Deutsche Forschungsgemeinschaft (German Research Foundation). NR 38 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAR PY 2015 VL 64 IS 3 BP 357 EP 366 DI 10.1007/s00262-014-1638-4 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CC4VC UT WOS:000350351200009 PM 25445815 ER PT J AU Stone, JR AF Stone, James R. TI Novel prognostic tissue markers in congestive heart failure SO CARDIOVASCULAR PATHOLOGY LA English DT Review DE Apoptosis; Proliferation; Ubiquitin; Cyclophilin A; Gremlin-1; Heterogeneous nuclear ribonucleoprotein C ID IDIOPATHIC DILATED CARDIOMYOPATHY; EUROPEAN CARDIOVASCULAR PATHOLOGY; PARTIAL LEFT VENTRICULECTOMY; NUCLEAR RIBONUCLEOPROTEIN-C; MESSENGER-RNA BINDING; ENDOMYOCARDIAL BIOPSY; HYDROGEN-PEROXIDE; PHYSIOLOGICAL LEVELS; INTIMAL HYPERPLASIA; RISK STRATIFICATION AB Heart failure is a relatively common disorder associated with high morbidity, mortality, and economic burden. Better tools to predict outcomes for patients with heart failure could allow for better decision making concerning patient treatment and management and better utilization of health care resources. Endomyocardial biopsy offers a mechanism to pathologically diagnose specific diseases in patients with heart failure, but such biopsies can often be negative, with no specific diagnostic information. Novel tissue markers in endomyocardial biopsies have been identified that may be useful in assessing prognosis in heart failure patients. Such tissue markers include ubiquitin, Gremlin-1, cyclophilin A, and heterogeneous nuclear ribonucleoprotein C. In some cases, tissue markers have been found to be independent of and even superior to clinical indices and serum markers in predicting prognosis for heart failure patients. In some cases, these novel tissue markers appear to offer prognostic information even in the setting of an otherwise negative endomyocardial biopsy. (C) 2014 Elsevier Inc. All rights reserved. C1 [Stone, James R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stone, James R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Simches Res Bldg Room 8236,185 Cambridge St CPZN, Boston, MA 02114 USA. EM jrstone@partners.org FU Massachusetts General Hospital FX This work was funded by Massachusetts General Hospital. NR 55 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 EI 1879-1336 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD MAR-APR PY 2015 VL 24 IS 2 BP 65 EP 70 DI 10.1016/j.carpath.2014.07.010 PG 6 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA CC3EY UT WOS:000350230000001 PM 25453729 ER PT J AU Vergallo, R Joye, R Barlis, P Jia, HB Tian, JW Soeda, T Minami, Y Hu, SN Dauerman, HL Toma, C Chan, J Lee, H Biasucci, LM Crea, F Jang, IK AF Vergallo, Rocco Joye, Russell Barlis, Peter Jia, Haibo Tian, Jinwei Soeda, Tsunenari Minami, Yoshiyasu Hu, Sining Dauerman, Harold L. Toma, Catalin Chan, James Lee, Hang Biasucci, Luigi Marzio Crea, Filippo Jang, Ik-Kyung TI Bivalirudin Versus Unfractionated Heparin for Residual Thrombus Burden: A Frequency-Domain Optical Coherence Tomography Study SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bivalirudin; unfractionated heparin; thrombus; optical coherence tomography ID PERCUTANEOUS CORONARY INTERVENTION; ELEVATION MYOCARDIAL-INFARCTION; CLOPIDOGREL TREATMENT; STENT THROMBOSIS; ELUTING STENTS; PRIMARY PCI; TRIAL; ABCIXIMAB; PLATELET; PLUS AB ObjectivesThis study aimed to compare the effect of bivalirudin and unfractionated heparin (UFH) on residual thrombus burden assessed by frequency-domain optical coherence tomography (FD-OCT), and on angiographic indices of microvascular obstruction (MVO). BackgroundThe efficacy of bivalirudin to inhibit thrombus formation inside the stent during percutaneous coronary interventions (PCI) as compared to UFH is unknown. MethodsSixty patients with coronary artery disease who underwent post-PCI FD-OCT were studied, including 20 patients treated with bivalirudin and 40 control patients treated with UFH, matched by clinical presentation, stent characteristics, and periprocedural medications. In-stent thrombus volume, thrombus score (number of quadrants with thrombus), and thrombus type (white/red) were assessed by FD-OCT. Thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), and Quantitative Blush Evaluator (QuBE) score were recorded. ResultsPatients treated with bivalirudin showed similar thrombus volume (0.14 mm(3) [0.00-0.88] vs. 0.13 mm(3) [0.00-0.63], P=0.962), thrombus score (10 [0-25] vs. 8 [0-21], P=0.849) and thrombus length (1.70 mm [0.00-4.10] vs. 1.40 mm [0.00-4.05], P=0.968], as compared with patients treated with UFH. Patients in the bivalirudin group showed lower proportion of white thrombus (55.5% vs. 78.6%, P=0.016). There was no significant difference in TIMI flow grade, cTFC, and QuBE score between the two groups. ConclusionsThe present study showed similar residual thrombus burden and angiographic indices of MVO immediately after PCI between patients treated with bivalirudin and those treated with UFH. (c) 2014 Wiley Periodicals, Inc. C1 [Vergallo, Rocco; Joye, Russell; Jia, Haibo; Tian, Jinwei; Soeda, Tsunenari; Minami, Yoshiyasu; Hu, Sining; Chan, James; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Barlis, Peter] Univ Melbourne, Melbourne Med Sch, Melbourne, Vic 3010, Australia. [Dauerman, Harold L.] Univ Vermont, Coll Med, Div Cardiol, Burlington, VT USA. [Toma, Catalin] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Biasucci, Luigi Marzio; Crea, Filippo] Univ Cattolica Sacro Cuore, Dept Cardiovasc Med, I-00168 Rome, Italy. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@mgh.harvard.edu OI biasucci, luigi m/0000-0002-6921-6497 FU National Natural Science Foundation of China [81200076, 81300201]; Italian Society of Cardiology Award for Research Abroad; Dr. John Nam Research Fellowship grant; Light-Lab Imaging/St. Jude Medical FX Contract grant sponsor: National Natural Science Foundation of China; Contract grant numbers: 81200076; 81300201.; Contract grant sponsor: Italian Society of Cardiology Award for Research Abroad, Dr. John Nam Research Fellowship grant, Light-Lab Imaging/St. Jude Medical.. NR 23 TC 5 Z9 5 U1 0 U2 6 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 MAR PY 2015 VL 85 IS 4 BP 575 EP 582 DI 10.1002/ccd.25631 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CC2VN UT WOS:000350202900015 PM 25115992 ER PT J AU Wang, HX Sharma, C Knoblich, K Granter, SR Hemler, ME AF Wang, Hong-Xing Sharma, Chandan Knoblich, Konstantin Granter, Scott R. Hemler, Martin E. TI EWI-2 negatively regulates TGF-beta signaling leading to altered melanoma growth and metastasis SO CELL RESEARCH LA English DT Article DE melanoma; EWI-2/IgSF8; TGF-beta 1; tetraspanins; CD9; CD81 ID EPITHELIAL-MESENCHYMAL TRANSITION; TRANSFORMING GROWTH-FACTOR-BETA-1; CD9-ASSOCIATED PROTEIN; CUTANEOUS MELANOMA; TETRASPANIN CD9; CELL MOTILITY; CD81 PARTNER; CANCER CELLS; EXPRESSION; INVASION AB In normal melanocytes, TGF-beta signaling has a cytostatic effect. However, in primary melanoma cells, TGF-beta-induced cytostasis is diminished, thus allowing melanoma growth. Later, a second phase of TGF-beta signaling supports melanoma EMT-like changes, invasion and metastasis. In parallel with these "present-absent-present" TGF-beta signaling phases, cell surface protein EWI motif-containing protein 2 (EWI-2 or IgSF8) is "absent-present-absent" in melanocytes, primary melanoma, and metastatic melanoma, respectively, suggesting that EWI-2 may serve as a negative regulator of TGF-beta signaling. Using melanoma cell lines and melanoma short-term cultures, we performed RNAi and overexpression experiments and found that EWI-2 negatively regulates TGF-beta signaling and its downstream events including cytostasis (in vitro and in vivo), EMT-like changes, cell migration, CD271-dependent invasion, and lung metastasis (in vivo). When EWI-2 is present, it associates with cell surface tetraspanin proteins CD9 and CD81-molecules not previously linked to TGF-beta signaling. Indeed, when associated with EWI-2, CD9 and CD81 are sequestered and have no impact on T beta R2-T beta R1 association or TGF-beta signaling. However, when EWI-2 is knocked down, CD9 and CD81 become available to provide critical support for T beta R2-T beta R1 association, thus markedly elevating TGF-beta signaling. Consequently, all of those TGF-beta-dependent functions specifically arising due to EWI-2 depletion are reversed by blocking or depleting cell surface tetraspanin proteins CD9 or CD81. These results provide new insights into regulation of TGF-beta signaling in melanoma, uncover new roles for tetraspanins CD9 and CD81, and strongly suggest that EWI-2 could serve as a favorable prognosis indicator for melanoma patients. C1 [Wang, Hong-Xing; Sharma, Chandan; Knoblich, Konstantin; Hemler, Martin E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Wang, Hong-Xing; Sharma, Chandan; Knoblich, Konstantin; Hemler, Martin E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Granter, Scott R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. EM martin_hemler@dfci.harvard.edu RI Knoblich, Konstantin/B-5980-2009 OI Knoblich, Konstantin/0000-0002-5646-837X FU National Institutes of Health [CA42368] FX This work was supported by the National Institutes of Health (CA42368 to MEH). NR 50 TC 4 Z9 4 U1 1 U2 3 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 MAR PY 2015 VL 25 IS 3 BP 370 EP 385 DI 10.1038/cr.2015.17 PG 16 WC Cell Biology SC Cell Biology GA CC7SN UT WOS:000350568800011 PM 25656846 ER PT J AU Parsons, K Nakatani, Y Nguyen, MD AF Parsons, Kari Nakatani, Yoshihiro Minh Dang Nguyen TI p600/UBR4 in the central nervous system SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE p600; UBR4; CNS; Brain; Neurons; Neurological diseases ID END RULE PATHWAY; JOHANSON-BLIZZARD-SYNDROME; COPY-NUMBER VARIATION; E3 UBIQUITIN LIGASES; SPINDLE ORIENTATION; NEURONAL MIGRATION; E7 ONCOPROTEIN; UBR BOX; PHOTOCONDUCTIVE STIMULATION; DEVELOPMENTAL-DISABILITIES AB A decade ago, the large 600 kDa mammalian protein p600 (also known as UBR4) was discovered as a multifunctional protein with roles in anoikis, viral transformation and protein degradation. Recently, p600 has emerged as a critical protein in the mammalian brain with roles in neurogenesis, neuronal migration, neuronal signaling and survival. How p600 integrates these apparently unrelated functions to maintain tissue homeostasis and murine survival remains unclear. The common molecular basis underlying many of the actions of p600 suggests, however, certain conservation and transposition of these functions across systems. In this review, we summarize the central nervous system functions of p600 and propose new perspectives on its biological complexity in neuronal physiology and neurological diseases. C1 [Parsons, Kari; Minh Dang Nguyen] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Parsons, Kari; Minh Dang Nguyen] Univ Calgary, Hotchkiss Brain Inst, Dept Cell Biol & Anat, Calgary, AB T2N 4N1, Canada. [Parsons, Kari; Minh Dang Nguyen] Univ Calgary, Dept Biochem & Mol Biol, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Nakatani, Yoshihiro] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Nguyen, MD (reprint author), Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. EM kalparso@ucalgary.ca; Yoshihiro_Nakatani@dfci.harvard.edu; mdnguyen@ucalgary.ca FU Canadian Institutes of Health Research (CIHR); Alberta Innovates Health Solutions (AIHS); Human Frontier Science Program Organization; CIHR; AIHS FX The work on p600 is supported by the Canadian Institutes of Health Research (CIHR) (MDN) and Alberta Innovates Health Solutions (AIHS) (MDN). MDN held a Career Development Award from the Human Frontier Science Program Organization, a New Investigator Award from the CIHR and a Scholar Award from the AIHS. KP received an AIHS scholarship. NR 109 TC 2 Z9 2 U1 0 U2 12 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X EI 1420-9071 J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 2015 VL 72 IS 6 BP 1149 EP 1160 DI 10.1007/s00018-014-1788-8 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CC4EJ UT WOS:000350303300008 PM 25424645 ER PT J AU Camargo, CA AF Camargo, C. A., Jr. TI Gestational weight gain and offspring asthma: A novel opportunity for primary prevention research SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Editorial Material ID BODY-MASS INDEX; OBESITY; DISEASE; RISK C1 [Camargo, C. A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 11 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-7894 EI 1365-2222 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD MAR PY 2015 VL 45 IS 3 BP 544 EP 546 DI 10.1111/cea.12436 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA CC6DT UT WOS:000350455800001 PM 25711133 ER PT J AU Soderling, E ElSalhy, M Honkala, E Fontana, M Flannagan, S Eckert, G Kokaras, A Paster, B Tolvanen, M Honkala, S AF Soderling, Eva ElSalhy, Mohamed Honkala, Eino Fontana, Margherita Flannagan, Susan Eckert, George Kokaras, Alexis Paster, Bruce Tolvanen, Mimmi Honkala, Sisko TI Effects of short-term xylitol gum chewing on the oral microbiome SO CLINICAL ORAL INVESTIGATIONS LA English DT Article DE Xylitol; Sorbitol; HOMIM; Mutans streptococci; Microbiota ID RANDOMIZED-CLINICAL-TRIAL; HIGH-DOSE XYLITOL; MUTANS STREPTOCOCCI; CARIES PREVENTION; SCHOOL-SATISFACTION; LIFE-SATISFACTION; SUGAR ALCOHOLS; DENTAL-CARIES; PLAQUE PH; SCHOOLCHILDREN AB The aim of this study was to determine the effects of short-term xylitol gum chewing on the salivary microbiota of children. The study was a randomised, controlled, double-blind trial. Healthy children used xylitol chewing gum (xylitol group, n = 35) or sorbitol chewing gum (control group, n = 38) for 5 weeks. The daily dose of xylitol/sorbitol was approximately 6 g/day. At baseline and at the end of the test period, unstimulated and paraffin-stimulated saliva were collected. The microbial composition of the saliva was assessed using human oral microbe identification microarray (HOMIM). Mutans streptococci (MS) were plate cultured. As judged by HOMIM results, no xylitol-induced changes in the salivary microbiota took place in the xylitol group. In the control group, Veillonella atypica showed a significant decrease (p = 0.0001). The xylitol gum chewing decreased viable counts of MS in both stimulated (p = 0.006) and unstimulated (p = 0.002) saliva, but similar effects were also seen in the control group. The use of xylitol gum decreased MS, in general, but did not change the salivary microbial composition. Short-term consumption of xylitol had no impact on the composition of the salivary microbiota, but resulted in a decrease in the levels of MS. C1 [Soderling, Eva; Tolvanen, Mimmi] Univ Turku, Inst Dent, FIN-20520 Turku, Finland. [ElSalhy, Mohamed; Honkala, Eino; Honkala, Sisko] Kuwait Univ, Fac Dent, Safat 13110, Kuwait. [Fontana, Margherita; Flannagan, Susan; Eckert, George] Univ Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA. [Eckert, George] Indiana Univ, Sch Med, Dept Biostat, Indianapolis, IN 46202 USA. [Kokaras, Alexis; Paster, Bruce] Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA. [Paster, Bruce] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Soderling, E (reprint author), Univ Turku, Inst Dent, FIN-20520 Turku, Finland. EM eva.soderling@utu.fi OI Fontana, Margherita/0000-0003-2357-7534; ElSalhy, Mohamed/0000-0002-7410-457X FU TEKES, Finland; STABPRO project; Finnish Dental Society Apollonia; Kuwait University [DD02/10, GD01/11, SRUL02/13] FX The excellent technical assistance of biomedical research technician Oona Hallfors (Institute of Dentistry, University of Turku, Finland) and Anisha Varghese (Faculty of Dentistry, University of Kuwait, Kuwait) is gratefully acknowledged. The STABPRO project (funded by TEKES, Finland) and Finnish Dental Society Apollonia are acknowledged for providing funding for the study. This study was also supported by Kuwait University grants DD02/10, GD01/11, SRUL02/13. NR 41 TC 6 Z9 6 U1 4 U2 34 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1432-6981 EI 1436-3771 J9 CLIN ORAL INVEST JI Clin. Oral Investig. PD MAR PY 2015 VL 19 IS 2 BP 237 EP 244 DI 10.1007/s00784-014-1229-y PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CC4VT UT WOS:000350353300009 PM 24663814 ER PT J AU Rauch, SAM King, AP Abelson, J Tuerk, PW Smith, E Rothbaum, BO Clifton, E Defever, A Liberzon, I AF Rauch, Sheila A. M. King, Anthony P. Abelson, James Tuerk, Peter W. Smith, Erin Rothbaum, Barbara O. Clifton, Erin Defever, Andrew Liberzon, Israel TI BIOLOGICAL AND SYMPTOM CHANGES IN POSTTRAUMATIC STRESS DISORDER TREATMENT: A RANDOMIZED CLINICAL TRIAL SO DEPRESSION AND ANXIETY LA English DT Article DE PTSD; cortisol; treatment; exposure therapy; cognitive behavioral therapy; veteran ID CORTISOL-LEVELS; PROLONGED EXPOSURE; FOLLOW-UP; PTSD; THERAPY; RESPONSES; VETERANS; NEUROENDOCRINE; VALIDATION; SURVIVORS AB BackgroundUnderstanding cognitive and biological mechanisms of PTSD treatment can help refine treatments and increase rates of response. MethodsThirty-six veterans with PTSD were randomly assigned to receive Prolonged exposure therapy (PE) or Present-Centered therapy (PCT). We examined symptoms, trauma-related cognitions, and two indices of HPA axis function (cortisol awakening response and cortisol response to a script-driven imagery task). ResultsThirty veterans started treatment and 26 completed. PE resulted in significantly more symptom reduction than PCT (P=.008). High treatment responders collapsed across treatments showed nominally higher cortisol levels measured at pretreatment 30 min after trauma script exposure compared to low responders (P=.08). At midtreatment, high treatment responders showed higher cortisol levels throughout the imagery task (Ps=.03-.04). There were no differences between high and low treatment responders at posttreatment. Thoughts of incompetence (F (1.6, 35.8)=16.8, P=.000) and a dangerous world (F (1.3, 29.9)=8.2, P=.004) significantly improved over time in high treatment responders but showed no change in low responders. Script-associated cortisol response prior to treatment and reductions in thoughts of incompetence accounted for 83% of the variance in reductions in PTSD severity with PE. ConclusionsBoth increased cortisol response to personal trauma script prior to PTSD therapy and reductions in cognitive symptoms of PTSD were significantly and uniquely related to reductions in the core symptoms of PTSD in PE. However, contrary to our hypotheses, cortisol measures were not related to cognitive changes. C1 [Rauch, Sheila A. M.; King, Anthony P.; Smith, Erin; Clifton, Erin; Defever, Andrew; Liberzon, Israel] VA Ann Arbor Healthcare Syst, PTSD Clin Team, Ann Arbor, MI USA. [Rauch, Sheila A. M.; King, Anthony P.; Abelson, James; Liberzon, Israel] Univ Michigan Med Sch, Dept Psychiat, Ann Arbor, MI USA. [Tuerk, Peter W.] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. [Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Rothbaum, Barbara O.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. RP Rauch, SAM (reprint author), VA Ann Arbor Healthcare Syst, PTSD Clin Team, 2215 Fuller Rd 116c, Ann Arbor, MI 48105 USA. EM sherauch@med.umich.edu RI Rauch, Sheila/K-4450-2015; OI Rauch, Sheila/0000-0001-9686-4011; King, Anthony/0000-0002-0764-9625; Liberzon, Israel/0000-0002-4990-556X FU VA Office of Research and Development Clinical Sciences Research and Development (PI: Rauch); VHA; DOD FX This article was based on work supported by a Career Development Award (CDA-2) from the VA Office of Research and Development Clinical Sciences Research and Development (PI: Rauch). Dr. Rauch has received grant funding from VHA and DOD. Dr. Liberzon has received grant funding from DOD and NIH. Preliminary results from this study were presented at 2010 and 2011 Annual Meeting of the American College of Neuropsychopharmacology and the 2011 Anxiety Disorders Association of America Conference. Erin Clifton's affiliation has changed since her work on this project. Her current affiliation is Department of Psychology, Case Western Reserve University. NR 37 TC 9 Z9 10 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAR PY 2015 VL 32 IS 3 BP 204 EP 212 DI 10.1002/da.22331 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CC6LD UT WOS:000350475500007 PM 25639570 ER PT J AU Maguire, LH Thomas, AR Goldstein, AM AF Maguire, Lillias H. Thomas, Alyssa R. Goldstein, Allan M. TI Tumors of the Neural Crest: Common Themes in Development and Cancer SO DEVELOPMENTAL DYNAMICS LA English DT Review DE neural crest cells; neurocristopathies; neural crest-derived tumors; epithelial mesenchymal transition ID MULTIPLE ENDOCRINE NEOPLASIA; EPITHELIAL-MESENCHYMAL TRANSITION; MEDULLARY-THYROID CARCINOMA; CHEMOKINE RECEPTOR CXCR4; CELL-CELL ADHESION; E-CADHERIN; N-CADHERIN; PERIPHERAL-NERVE; GENE-EXPRESSION; NEUROFIBROMATOSIS TYPE-1 AB The neural crest (NC) is a remarkable transient structure in the vertebrate embryo that gives rise to a highly versatile population of pluripotent cells that contribute to the formation of multiple tissues and organs throughout the body. In order to achieve their task, NC-derived cells have developed specialized mechanisms to promote (1) their transition from an epithelial to a mesenchymal phenotype, (2) their capacity for extensive migration and cell proliferation, and (3) their ability to produce diverse cell types largely depending on the microenvironment encountered during and after their migratory path. Following embryogenesis, these same features of cellular motility, invasion, and proliferation can become a liability by contributing to tumorigenesis and metastasis. Ample evidence has shown that cancer cells have cleverly co-opted many of the genetic and molecular features used by developing NC cells. This review focuses on tumors that arise from NC-derived tissues and examines mechanistic themes shared during their oncogenic and metastatic development with embryonic NC cell ontogeny. Developmental Dynamics 244:311-322, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Maguire, Lillias H.; Thomas, Alyssa R.; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. RP Goldstein, AM (reprint author), Massachusetts Gen Hosp, Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org NR 148 TC 12 Z9 12 U1 7 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD MAR PY 2015 VL 244 IS 3 SI SI BP 311 EP 322 DI 10.1002/dvdy.24226 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA CC6MR UT WOS:000350479700008 PM 25382669 ER PT J AU Jacobson, AM Nathan, DM AF Jacobson, Alan M. Nathan, David M. TI Saul Genuth, MD: Clinical Researcher and Leader in Developing Modern Diabetes Treatment SO DIABETES CARE LA English DT Editorial Material ID COMPLICATIONS TRIAL/EPIDEMIOLOGY; INSULIN-SECRETION; INTERVENTIONS; OBESITY; MICE; PROGRESSION; MELLITUS; DELIVERY; THERAPY; DISEASE C1 [Jacobson, Alan M.] Winthrop Univ Hosp, Res Inst, Mineola, NY 11501 USA. [Jacobson, Alan M.] Stony Brook Sch Med, Mineola, NY USA. [Nathan, David M.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA. RP Jacobson, AM (reprint author), Winthrop Univ Hosp, Res Inst, Mineola, NY 11501 USA. EM amjacobson@winthrop.org NR 25 TC 1 Z9 1 U1 0 U2 1 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 MAR PY 2015 VL 38 IS 3 BP 347 EP 351 DI 10.2337/dc14-1396 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CC4EN UT WOS:000350303700016 PM 25715411 ER PT J AU Hass, J Walton, E Kirsten, H Turner, J Wolthusen, R Roessner, V Sponheim, SR Holt, D Gollub, R Calhoun, VD Ehrlich, S AF Hass, Johanna Walton, Esther Kirsten, Holger Turner, Jessica Wolthusen, Rick Roessner, Veit Sponheim, Scott R. Holt, Daphne Gollub, Randy Calhoun, Vince D. Ehrlich, Stefan TI Complexin2 modulates working memory-related neural activity in patients with schizophrenia SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE Complexin2; Imaging genetics; Intermediate phenotype; Working memory; Frontoparietal circuit; Schizophrenia ID DORSOLATERAL PREFRONTAL CORTEX; GENOME-WIDE ASSOCIATION; SYNAPTIC PLASTICITY; MESSENGER-RNAS; RISK-FACTORS; FMRI; DYSFUNCTION; POPULATION; RELATIVES; DISEASE AB The specific contribution of risk or candidate gene variants to the complex phenotype of schizophrenia is largely unknown. Studying the effects of such variants on brain function can provide insight into disease-associated mechanisms on a neural systems level. Previous studies found common variants in the complexin2 (CPLX2) gene to be highly associated with cognitive dysfunction in schizophrenia patients. Similarly, cognitive functioning was found to be impaired in Cplx2 gene-deficient mice if they were subjected to maternal deprivation or mild brain trauma during puberty. Here, we aimed to study seven common CPLX2 single-nucleotide polymorphisms (SNPs) and their neurogenetic risk mechanisms by investigating their relationship to a schizophrenia-related functional neuroimaging intermediate phenotype. We examined functional MRI and genotype data collected from 104 patients with DSM-IV-diagnosed schizophrenia and 122 healthy controls who participated in the Mind Clinical Imaging Consortium study of schizophrenia. Seven SNPs distributed over the whole CPLX2 gene were tested for association with working memory-elicited neural activity in a frontoparietal neural network. Three CPLX2 SNPs were significantly associated with increased neural activity in the dorsolateral prefrontal cortex and intraparietal sulcus in the schizophrenia sample, but showed no association in healthy controls. Since increased working memory-related neural activity in individuals with or at risk for schizophrenia has been interpreted as 'neural inefficiency,' these findings suggest that certain variants of CPLX2 may contribute to impaired brain function in schizophrenia, possibly combined with other deleterious genetic variants, adverse environmental events, or developmental insults. C1 [Hass, Johanna; Walton, Esther; Wolthusen, Rick; Roessner, Veit; Ehrlich, Stefan] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Fac Med Carl Gustav Carus, D-01307 Dresden, Germany. [Kirsten, Holger] Univ Leipzig, IMISE, D-04109 Leipzig, Germany. [Kirsten, Holger] Univ Leipzig, LIFE Leipzig Interdisciplinary Res Cluster Genet, D-04109 Leipzig, Germany. [Turner, Jessica; Calhoun, Vince D.] MIND Res Network, Albuquerque, NM USA. [Wolthusen, Rick; Holt, Daphne; Gollub, Randy; Ehrlich, Stefan] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wolthusen, Rick; Holt, Daphne; Gollub, Randy; Ehrlich, Stefan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Ctr Magnet Resonance Res, Minneapolis, MN 55455 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. RP Ehrlich, S (reprint author), Tech Univ Dresden, Dept Child & Adolescent Psychiat, Fac Med Carl Gustav Carus, Fetscherstr 74, D-01307 Dresden, Germany. EM transden.lab@gmail.com OI Walton, Esther/0000-0002-0935-2200; Gollub, Randy L./0000-0002-9434-4044 FU National Institutes of Health [NIH/NCRR P41RR14075]; Department of Energy [DE-FG02-99ER62764]; MIND Research Network; Morphometry BIRN [1U24, RR021382A]; Function BIRN [U24RR021992-01, NIH.NCRR MO1 RR025758-01]; NARSAD; Deutsche Forschungsgemeinschaft FX This work was supported by the National Institutes of Health (NIH/NCRR P41RR14075), Department of Energy (DE-FG02-99ER62764), MIND Research Network, Morphometry BIRN (1U24, RR021382A), Function BIRN (U24RR021992-01, NIH.NCRR MO1 RR025758-01), NARSAD Young Investigator Grant (SE), and the Deutsche Forschungsgemeinschaft (Research Fellowship to SE). NR 61 TC 5 Z9 5 U1 2 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0940-1334 EI 1433-8491 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD MAR PY 2015 VL 265 IS 2 BP 137 EP 145 DI 10.1007/s00406-014-0550-4 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CC4FC UT WOS:000350305500006 PM 25297695 ER PT J AU Shaaya, EA Pollack, SF Boronat, S Davis-Cooper, S Zella, GC Thibert, RL AF Shaaya, Elias A. Pollack, Sarah F. Boronat, Susana Davis-Cooper, Shelby Zella, Garrett C. Thibert, Ronald L. TI Gastrointestinal problems in 15q duplication syndrome SO EUROPEAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE 15q duplication syndrome; Constipation; Dup15q; GI; GI reflux ID OF-THE-LITERATURE; INTERSTITIAL DUPLICATION; AUTISM; DISORDERS; CHILDREN; REGION; ASDS AB Chromosome 15q duplication syndrome ( Dup15q syndrome) is a neurodevelopmental disorder involving copy number gains of the maternal chromosome 15q11.2-q13 region, characterized by intellectual disability, developmental delay, autism spectrum disorder (ASD), and epilepsy. Gastrointestinal (GI) problems in Dup15q syndrome have been reported only rarely, mostly focused on neonatal feeding difficulties. A retrospective review of the medical records of 46 patients with Dup15q syndrome was conducted to assess GI issues and their treatments in this population. GI symptoms were present in 76.7% of subjects with an isodicentric duplication and 87.5% with an interstitial duplication. There was no clear association between GI issues and ASD, with symptoms occurring in 78.9% of all subjects and 78.2% of ASD subjects. The most commonly reported symptoms were gastroesophageal reflux (56.7%) and constipation (60%), with 30% of subjects reporting both. The most common treatments were polyethylene glycol for constipation and proton pump inhibitors for reflux. Behaviors such as irritability and aggressiveness improved with treatment of GI symptoms in several subjects. The results indicate that GI symptoms are common in Dup15q syndrome and may have an atypical presentation. Diagnosis may be difficult, especially in individuals who are nonverbal or minimally verbal, so increased awareness is critical for early diagnosis and treatment. (C) 2015 Elsevier Masson SAS. All rights reserved. C1 [Shaaya, Elias A.; Pollack, Sarah F.; Boronat, Susana; Davis-Cooper, Shelby; Thibert, Ronald L.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. [Shaaya, Elias A.; Pollack, Sarah F.; Boronat, Susana; Davis-Cooper, Shelby; Thibert, Ronald L.] Dup15q Ctr, Boston, MA USA. [Zella, Garrett C.] Tufts Med Ctr, Floating Hosp Children, Boston, MA USA. [Zella, Garrett C.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Thibert, Ronald L.] Harvard Univ, Sch Med, Boston, MA USA. RP Thibert, RL (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM rthibert@mgh.harvard.edu FU Dup15q Alliance FX We would like to thank the Dup15q Alliance for their support of this study. We would also like to thank all of the families who have visited the Dup15q Center at the Massachusetts General Hospital. NR 14 TC 1 Z9 1 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1769-7212 EI 1878-0849 J9 EUR J MED GENET JI Eur. J. Med. Genet. PD MAR PY 2015 VL 58 IS 3 BP 191 EP 193 DI 10.1016/j.ejmg.2014.12.012 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA CC3EP UT WOS:000350228700013 PM 25573720 ER PT J AU Kapoor, S Thorn, BE Bandy, O Clements, KL AF Kapoor, S. Thorn, B. E. Bandy, O. Clements, K. L. TI Pain referents used to respond to the Pain Catastrophizing Scale SO EUROPEAN JOURNAL OF PAIN LA English DT Article ID COGNITIVE-BEHAVIORAL TREATMENT; BACK-PAIN; PREDICTORS; MEMORIES; HEADACHE; THERAPY; TRIAL AB BackgroundPain catastrophizing has emerged as a highly important construct in pain research. The Pain Catastrophizing Scale (PCS) is a widely used self-report measure used to determine a person's level of pain catastrophizing, assumed to be associated with an ongoing, recalled or anticipated pain experience. In practice, instructions for self-reporting catastrophizing typically do not provide a specific pain referent, even when assessing patients with chronic pain. Researchers have noted that it is not known what type of pain participants are referring to when responding to a catastrophizing questionnaire. MethodIn the current study, 182 presumably healthy undergraduate students completed the PCS followed by a query regarding the pain referent used to complete the scale. In addition, they were asked if they have ever experienced chronic pain and to list their worst pain experience. ResultsThe most commonly used primary referents included pain due to acute injury (26.4%), headache (18.0%) and general physical pain (11.5%). The type of primary referent and the number of referents did not influence the catastrophizing scores. However, the catastrophizing scores were influenced by the context of the primary pain referent, i.e., whether the primary pain referent was non-chronic worst pain, both chronic and worst pain, chronic pain or unrelated to either chronic or worst pain. Notably, a larger than expected proportion of participants reported having experienced chronic pain (44.5%; n=81). ConclusionThe examination of pain referents while responding to a catastrophizing measure would add to our understanding of a person's pain experience and related catastrophic cognitions. C1 [Kapoor, S.; Thorn, B. E.; Bandy, O.] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA. [Clements, K. L.] Birmingham Vet Affairs Med Ctr, Dept Behav & Mental Hlth, Birmingham, AL USA. RP Thorn, BE (reprint author), Univ Alabama, Dept Psychol, Box 870348, Tuscaloosa, AL 35487 USA. EM bthorn@as.ua.edu NR 33 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1090-3801 EI 1532-2149 J9 EUR J PAIN JI Eur. J. Pain PD MAR PY 2015 VL 19 IS 3 BP 400 EP 407 DI 10.1002/ejp.561 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CC6HK UT WOS:000350465800013 PM 25059471 ER PT J AU Santos, Z Avci, P Hamblin, MR AF Santos, Zenildo Avci, Pinar Hamblin, Michael R. TI Drug discovery for alopecia: gone today, hair tomorrow SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE 5-alpha-reductase inhibitor; alopecia areata; androgenic alopecia; anti-androgen; baldness; chemotherapy-induced alopecia; hair follicle; low-level laser (light) therapy; stem cells; topical immunotherapy ID CHEMOTHERAPY-INDUCED ALOPECIA; MALE-PATTERN BALDNESS; GROWTH-PROMOTING ACTIVITY; GENOME-WIDE ASSOCIATION; FOLLICLE DERMAL PAPILLA; ANDROGENETIC ALOPECIA; IN-VITRO; STEM-CELLS; RAT MODEL; ANIMAL-MODELS AB Introduction: Hair loss or alopecia affects the majority of the population at some time in their life, and increasingly, sufferers are demanding treatment. Three main types of alopecia (androgenic [AGA], areata [AA] and chemotherapy-induced [CIA]) are very different, and have their own laboratory models and separate drug-discovery efforts. Areas covered: In this article, the authors review the biology of hair, hair follicle (HF) cycling, stem cells and signaling pathways. AGA, due to dihydrotesterone, is treated by 5-alpha reductase inhibitors, androgen receptor blockers and ATP-sensitive potassium channel-openers. AA, which involves attack by CD8(+)NK group 2D-positive (NKG2D(+)) T cells, is treated with immunosuppressives, biologics and JAK inhibitors. Meanwhile, CIA is treated by apoptosis inhibitors, cytokines and topical immunotherapy. Expert opinion: The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play. C1 [Santos, Zenildo; Avci, Pinar; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Santos, Zenildo; Avci, Pinar; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Avci, Pinar] Semmelweis Univ, Sch Med, Dept Dermatol Dermatooncol & Venerol, H-1085 Budapest, Hungary. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu FU CAPES [99999.002158/2014-00]; US NIH [R01AI050875]; Lexington International, Inc. FX Z Santos was supported by CAPES grant 99999.002158/2014-00. MR Hamblin was supported by US NIH grant R01AI050875. MR Hamblin is also a present member of the Transdermal Cap, Inc. scientific advisory board. He has also been a member of the scientific advisory board and received research support from Lexington International, Inc. Both companies manufacture LLLT devices for hair regrowth. 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 180 TC 3 Z9 3 U1 5 U2 46 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 EI 1746-045X J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD MAR PY 2015 VL 10 IS 3 BP 269 EP 292 DI 10.1517/17460441.2015.1009892 PG 24 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CC2YG UT WOS:000350210500007 PM 25662177 ER PT J AU Gukovsky, I Gukovskaya, AS AF Gukovsky, Ilya Gukovskaya, Anna S. TI Impaired Autophagy Triggers Chronic Pancreatitis: Lessons From Pancreas- Specific Atg5 Knockout Mice SO GASTROENTEROLOGY LA English DT Editorial Material ID CANCER; CELLS; INFLAMMATION; TRYPSINOGEN; ACTIVATION C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Gukovsky, I (reprint author), West Los Angeles VA Healthcare Ctr, Pancreat Res Grp, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA. EM igukovsk@ucla.edu FU NCI NIH HHS [P01 CA163200]; NIAAA NIH HHS [AA019730, R01 AA019730]; NIDDK NIH HHS [DK059936, DK098108, P01 DK098108, P30 DK041301, R01 DK059936] NR 28 TC 6 Z9 6 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2015 VL 148 IS 3 BP 501 EP 505 DI 10.1053/j.gastro.2015.01.012 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CB9QX UT WOS:000349968200017 PM 25613315 ER PT J AU Martins, M Williams, AH Comeau, M Marion, M Ziegler, JT Freedman, BI Merrill, JT Glenn, SB Kelly, JA Sivils, KM James, JA Guthridge, JM Alarcon-Riquelme, ME Bae, SC Kim, JH Kim, D Anaya, JM Boackle, SA Criswell, LA Kimberly, RP Alarcon, GS Brown, EE Vila, LM Petri, MA Ramsey-Goldman, R Niewold, TB Tsao, BP Gilkeson, GS Kamen, DL Jacob, CO Stevens, AM Gaffney, PM Harley, JB Langefeld, CD Fesel, C AF Martins, M. Williams, A. H. Comeau, M. Marion, M. Ziegler, J. T. Freedman, B. I. Merrill, J. T. Glenn, S. B. Kelly, J. A. Sivils, K. M. James, J. A. Guthridge, J. M. Alarcon-Riquelme, M. E. Bae, S-C Kim, J-H Kim, D. Anaya, J-M Boackle, S. A. Criswell, L. A. Kimberly, R. P. Alarcon, G. S. Brown, E. E. Vila, L. M. Petri, M. A. Ramsey-Goldman, R. Niewold, T. B. Tsao, B. P. Gilkeson, G. S. Kamen, D. L. Jacob, C. O. Stevens, A. M. Gaffney, P. M. Harley, J. B. Langefeld, C. D. Fesel, C. TI Genetic association of CD247 (CD3 zeta) with SLE in a large-scale multiethnic study SO GENES AND IMMUNITY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; RECEPTOR ZETA-CHAIN; T-CELLS; SUSCEPTIBILITY LOCI; DOWN-REGULATION; EXPRESSION; REPLICATION; VARIANTS; PHOSPHORYLATION AB A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3. chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3. are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 x 10(-4) < P < 4.15 x 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085- rs12144621-rs858554; G-G-A-G-A; P-hap = 2.12 x 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 x 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 x 10(-3) < P < 3.97 x 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P-meta = 2.66 x 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism. C1 [Martins, M.] Inst Mol Med, P-1649028 Lisbon, Portugal. [Martins, M.; Fesel, C.] Inst Gulbenkian Ciencias, Oeiras, Portugal. [Williams, A. H.; Comeau, M.; Marion, M.; Ziegler, J. T.] Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA. [Williams, A. H.; Comeau, M.; Marion, M.; Ziegler, J. T.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Freedman, B. I.] Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC USA. [Merrill, J. T.; Glenn, S. B.; Kelly, J. A.] Oklahoma Med Res Fdn, Clin Pharmacol Res Program, Oklahoma City, OK 73104 USA. [James, J. A.; Guthridge, J. M.; Alarcon-Riquelme, M. E.] Oklahoma Med Res Fdn, Arthritis & Clin Immunol Program, Oklahoma City, OK 73104 USA. [James, J. A.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Alarcon-Riquelme, M. E.] Pfizer Univ Granada Junta de Andalucia, Ctr Genom & Invest Oncol GENYO, Granada, Spain. [Bae, S-C; Kim, J-H; Kim, D.] Hanyang Univ, Hosp Rheumat Dis, Dept Rheumatol, Seoul 133791, South Korea. [Anaya, J-M] Univ Rosario, Ctr Autoimmune Dis Res CREA, Bogota, Colombia. [Boackle, S. A.] Univ Colorado, Sch Med, Div Rheumatol, Aurora, CO USA. [Criswell, L. A.] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA. [Kimberly, R. P.; Alarcon, G. S.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Brown, E. E.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Brown, E. E.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Vila, L. M.] Univ Puerto Rico Med Sci Campus, Dept Med, Div Rheumatol, San Juan, PR USA. [Petri, M. A.] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA. [Ramsey-Goldman, R.] Northwestern Univ, Sch Med, Div Rheumatol, Chicago, IL 60611 USA. [Niewold, T. B.] Mayo Clin, Div Rheumatol, Rochester, MN USA. [Niewold, T. B.] Mayo Clin, Dept Immunol, Rochester, MN USA. [Tsao, B. P.] Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA USA. [Gilkeson, G. S.; Kamen, D. L.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Jacob, C. O.] Univ So Calif, Dept Med, Los Angeles, CA USA. [Stevens, A. M.] Seattle Childrens Res Inst Arthrit Fdn, Ctr Immun & Immunotherapies, Seattle, WA USA. [Harley, J. B.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA. [Harley, J. B.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Cincinnati, OH 45229 USA. [Harley, J. B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. RP Martins, M (reprint author), Inst Mol Med, Av Prof Egas Moniz,Edificio Egas Moniz,P1C74, P-1649028 Lisbon, Portugal. EM mcmartins227@gmail.com RI Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249 FU National Institutes of Health [UL1RR025741] FX We thank the SLE patients and healthy controls for their collaboration in this study. We also thank the entire OMRF team for organizing this study. We thank all the authors of the 'Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus' (Yang et al. 2010) paper for sharing the data information on the GWAS results on the CD247 region. We also thank the University of Alabama Birmingham Center for Clinical and Translational Science (CCTS). This study was supported by the: National Institutes of Health grants (UL1RR025741) to RRG, Northwestern University Feinberg School of Medicine (K24AR002138, P602AR30692, P01AR49084) to RPK, GSA and EEB, University of Alabama Birmingham to LMP, National Institute of Arthritis and Musculoskeletal and Skin Diseases to RRG, UL1TR000165 and P01AI083194 to RPK, RO1AR43814 to BPT, University of California Los Angeles (P60AR053308, UL1TR000004) to LC, University of California San Francisco (AR43727) to MAP, Johns Hopkins University (R21AI070304) to SAB, University of Colorado School of Medicine (RO1AR057172) to COJ, University of Southern California (UL1RR025014 and R01AR051545-03) to AMS, Seattle Children's Research Institute Arthritis Foundation (UL1RR029882 and P60AR062755) to GSG and DLK, Medical University of South Carolina (P30AR53483, U19AI082714, P30GM103510, U01AI101934) to JAJ and JMG, AI063274, AR056360 and AI083194 to PMG, Oklahoma Medical Research Foundation (R37AI024717, P01083194, P01AR049084) to JH, Cincinnati Children's Hospital Medical Center; the US Departments of Defense (PR094002) to JH and Veterans Affairs to JH; the Alliance for Lupus Research to LC and BPT; a Kirkland Scholar Award to LC; Korea Healthcare technology R & D project (A121983) funded by the Ministry for Health and Welfare, Republic of Korea to SCB; the Swedish Research Council and Instituto de Salud Carlos III grant (PS09/ 00129) cofinanced by FEDER funds of the European Union to MEAR; Funda~ao para a Cincia e Tecnologia (FCT, Portugal) fellowships (SFRH/ BPD/ 29354/ 2006) to M Martins and (SFRH/ BPD/ 34648/ 2007) to CF. NR 44 TC 2 Z9 2 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 EI 1476-5470 J9 GENES IMMUN JI Genes Immun. PD MAR PY 2015 VL 16 IS 2 BP 142 EP 150 DI 10.1038/gene.2014.73 PG 9 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA CD0BV UT WOS:000350736100006 PM 25569266 ER PT J AU Amendola, LM Dorschner, MO Robertson, PD Salama, JS Hart, R Shirts, BH Murray, ML Tokita, MJ Gallego, CJ Kim, DS Bennett, JT Crosslin, DR Ranchalis, J Jones, KL Rosenthal, EA Jarvik, ER Itsara, A Turner, EH Herman, DS Schleit, J Burt, A Jamal, SM Abrudan, JL Johnson, AD Conlin, LK Dulik, MC Santani, A Metterville, DR Kelly, M Foreman, AKM Lee, K Taylor, KD Guo, XQ Crooks, K Kiedrowski, LA Raffe, LJ Gordon, O Machini, K Desnick, R Biesecker, LG Lubitz, SA Mulchandani, S Cooper, GM Joffe, S Richards, CS Yang, YP Rotter, JI Rich, SS O'Donne, CJ Berg, JS Spinner, NB Evans, JP Fullerton, SM Leppig, KA Bennett, RL Bird, T Sybert, VP Grady, WM Tabor, HK Kim, JH Bamshad, MJ Wilfond, B Motulsky, AG Scott, R Pritchard, CC Walsh, TD Burke, W Raskind, WH Byers, P Hisama, FM Rehm, H Nickerson, DA Jarvik, GP AF Amendola, Laura M. Dorschner, Michael O. Robertson, Peggy D. Salama, Joseph S. Hart, Ragan Shirts, Brian H. Murray, Mitzi L. Tokita, Mari J. Gallego, Carlos J. Kim, Daniel Seung Bennett, James T. Crosslin, David R. Ranchalis, Jane Jones, Kelly L. Rosenthal, Elisabeth A. Jarvik, Ella R. Itsara, Andy Turner, Emily H. Herman, Daniel S. Schleit, Jennifer Burt, Amber Jamal, Seema M. Abrudan, Jenica L. Johnson, Andrew D. Conlin, Laura K. Dulik, Matthew C. Santani, Avni Metterville, Danielle R. Kelly, Melissa Foreman, Ann Katherine M. Lee, Kristy Taylor, Kent D. Guo, Xiuqing Crooks, Kristy Kiedrowski, Lesli A. Raffe, Leslie J. Gordon, Ora Machini, Kalotina Desnick, Robe Biesecker, Leslie G. Lubitz, Steven A. Mulchandani, Surabhi Cooper, Greg M. Joffe, Steven Richards, C. Sue Yang, Yaoping Rotter, Jerome I. Rich, Stephen S. O'Donne, Christopher J. Berg, Jonathan S. Spinner, Nancy B. Evans, James P. Fullerton, Stephanie M. Leppig, Kathleen A. Bennett, Robin L. Bird, Thomas Sybert, Virginia P. Grady, William M. Tabor, Holly K. Kim, Jerry H. Bamshad, Michael J. Wilfond, Benjamin Motulsky, Arno G. Scott, Ronald Pritchard, Colin C. Walsh, Tom D. Burke, Wylie Raskind, Wendy H. Byers, Peter Hisama, Fuki M. Rehm, Heidi Nickerson, Debbie A. Jarvik, Gail P. TI Actionable exomic incidental findings in 6503 participants: challenges of variant classification SO GENOME RESEARCH LA English DT Article ID MESSENGER-RNA DECAY; GENOMIC SEQUENCE; GENETIC-VARIANTS; MUTATIONS; IDENTIFICATION; INDIVIDUALS; INSIGHTS; DISEASE AB Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52(1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base. C1 [Amendola, Laura M.; Salama, Joseph S.; Hart, Ragan; Murray, Mitzi L.; Tokita, Mari J.; Gallego, Carlos J.; Bennett, James T.; Crosslin, David R.; Ranchalis, Jane; Rosenthal, Elisabeth A.; Jarvik, Ella R.; Itsara, Andy; Burt, Amber; Bennett, Robin L.; Sybert, Virginia P.; Motulsky, Arno G.; Scott, Ronald; Walsh, Tom D.; Burke, Wylie; Raskind, Wendy H.; Byers, Peter; Hisama, Fuki M.; Jarvik, Gail P.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Dorschner, Michael O.; Robertson, Peggy D.; Kim, Daniel Seung; Crosslin, David R.; Turner, Emily H.; Motulsky, Arno G.; Nickerson, Debbie A.; Jarvik, Gail P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Dorschner, Michael O.; Shirts, Brian H.; Turner, Emily H.; Herman, Daniel S.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Dorschner, Michael O.; Raskind, Wendy H.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Murray, Mitzi L.; Schleit, Jennifer; Byers, Peter] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Bennett, James T.; Jones, Kelly L.; Tabor, Holly K.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Jamal, Seema M.; Scott, Ronald] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA. [Abrudan, Jenica L.] Childrens Hosp Philadelphia, Dept Genet, Philadelphia, PA 19104 USA. [Abrudan, Jenica L.; Conlin, Laura K.; Dulik, Matthew C.; Santani, Avni; Spinner, Nancy B.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Johnson, Andrew D.; O'Donne, Christopher J.] NHLBI, Framingham Heart Study, Div Intramural Res, Framingham, MA 01702 USA. [Conlin, Laura K.; Santani, Avni; Spinner, Nancy B.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Dulik, Matthew C.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA. [Metterville, Danielle R.; Rehm, Heidi] Partners Healthcare, Mol Med Lab, Boston, MA 02115 USA. [Kelly, Melissa] Partners Healthcare Personalized Med, Boston, MA 02115 USA. [Foreman, Ann Katherine M.; Evans, James P.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Taylor, Kent D.; Guo, Xiuqing; Rotter, Jerome I.] Harbor UCLA, Los Angeles Biomed Res Inst, Translat Genom & Populat Sci, Torrance, CA 90502 USA. [Taylor, Kent D.; Guo, Xiuqing; Rotter, Jerome I.] Harbor UCLA, Dept Pediat, Torrance, CA 90502 USA. [Crooks, Kristy] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27514 USA. [Kiedrowski, Lesli A.] Univ Texas SW Med Ctr Dallas, Dept Canc Genet, Dallas, TX 75390 USA. [Raffe, Leslie J.; Gordon, Ora] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA. [Machini, Kalotina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Machini, Kalotina; Rehm, Heidi] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Desnick, Robe] Mt Sinai Hosp, Dept Genet & Genom Med, Div Med Genet, New York, NY 10029 USA. [Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Cooper, Greg M.] HudsonAlpha Inst Biotechnol Huntsville, Huntsville, AL 35806 USA. [Joffe, Steven] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Richards, C. Sue] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. [Yang, Yaoping] Harbor UCLA, Dept Pediat, Div Infect Dis, Torrance, CA 90502 USA. [Rich, Stephen S.] Harbor UCLA, Dept Pediat, Div Infect Dis, Torrance, CA 90502 USA. [Yang, Yaoping] Harbor UCLA, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Yang, Yaoping] Harbor UCLA, Dept Pediat, Torrance, CA 90502 USA. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. [O'Donne, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Fullerton, Stephanie M.] Massachusetts Gen Hosp, Dept Bioeth & Humanities, Seattle, WA 98195 USA. [Leppig, Kathleen A.; Nickerson, Debbie A.] Grp Hlth Cooperat Puget Sound, Genet Serv, Seattle, WA 98112 USA. [Bird, Thomas] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Bird, Thomas] Vet Affairs Puget Sound Hlth Care Syst Geriatr Re, Seattle, WA 98108 USA. [Sybert, Virginia P.] Grp Hlth Cooperat Puget Sound, Dermatol, Seattle, WA 98112 USA. [Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Grady, William M.] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. [Tabor, Holly K.; Wilfond, Benjamin] Seattle Childrens Res Inst, Treuman Katz Ctr Pediat Bioeth, Washington, DC 98105 USA. [Kim, Jerry H.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Wilfond, Benjamin] Univ Washington, Dept Pediat, Div Bioeth, Seattle, WA 98195 USA. RP Amendola, LM (reprint author), Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. EM pair@u.washington.edu RI Burke, William/C-1203-2012; Johnson, Andrew/G-6520-2013; OI Walsh, Tom/0000-0002-8875-0310; Lee, Kristy/0000-0002-8338-7989; Turner, Emily/0000-0001-9040-9229 FU NIH, NHGRI/NCI [U01HG006507, U01HG007307, U01HG006375, U01HG006485, U01HG006500, U01HG006546, UM1HG007301, UM1HG007292, U01HG006487, U01HG006492, U41HG006834]; NIH/NIGMS [T32 GM007454, 1K23HL114724, 5P30CA015704]; Burroughs Wellcome Fund (WMG); Washington State Life Sciences Discovery Fund [2065508]; National Heart, Lung, and Blood Institute (NHLBI); NHLBI [RC2 HL-103010, RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2 HL-102926]; Prostate Cancer Foundation Young Investigator Award FX We thank Joshua Akey for sharing his group's ancestry analyses. This work was funded by the NIH, NHGRI/NCI U01HG006507, U01HG007307, U01HG006375, U01HG006485, U01HG006500, U01HG006546, UM1HG007301, UM1HG007292, U01HG006487, U01HG006492, U41HG006834, U41HG006834, NIH/NIGMS T32 GM007454, 1K23HL114724, 5P30CA015704, Burroughs Wellcome Fund (WMG), and Washington State Life Sciences Discovery Fund (2065508, to the Northwest Institute of Genetic Medicine). The authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute (NHLBI) and the contributions of the research institutions, study investigators, field staff, and study participants in creating this resource for biomedical research. Funding for GO ESP was provided by NHLBI grants RC2 HL-103010 (HeartGO), RC2 HL-102923 (LungGO), and RC2 HL-102924 (WHISP). The exome sequencing was performed through NHLBI grants RC2 HL-102925 (BroadGO) and RC2 HL-102926 (SeattleGO). Dr. Pritchard is supported by a 2013 Prostate Cancer Foundation Young Investigator Award. The NEXT Medicine return of results committee included A.M., B.W., B.S., C.G., D.N., F.H., G.J, J.P.E., J.K., J.B., K.L., L.A., M.D., M.M., P.B., R.B., R.S., S.M.F., T.B., V.S., W.R., W.G., and W.B. The variant reviewers were A.J., A.D.J., A.S., B.S., C.G., D.H., D.K., ER., E.J., E.T., F.H., Gj., H.T., J.B., J.R., J.S., J.R., J.K., J.B., J.S., K.F., K.J., K.T., K.C., K.L., L.A., L.C., L.K., L.B., L.R., M.T., M.D., M.D., M.M., N.S., O.G., P.B., R.H., R.B., R.S., S.R., S.M., T.W., W.R., W.B., and X.G. NR 28 TC 57 Z9 57 U1 2 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD MAR PY 2015 VL 25 IS 3 BP 305 EP 315 DI 10.1101/gr.183483.114 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CC7DA UT WOS:000350526700001 PM 25637381 ER PT J AU Kim, H Zheng, SY Amini, SS Virk, SM Mikkelsen, T Brat, DJ Grimsby, J Sougnez, C Muller, F Hu, J Sloan, AE Cohen, ML Van Meir, EG Scarpace, L Laird, PW Weinstein, JN Lander, ES Gabrie, S Getz, G Meyerson, M Chin, L Barnholtz-Sloan, JS Verhaak, RGW AF Kim, Hoon Zheng, Siyuan Amini, Seyed S. Virk, Selene M. Mikkelsen, Tom Brat, Daniel J. Grimsby, Jonna Sougnez, Carrie Muller, Florian Hu, Jian Sloan, Andrew E. Cohen, Mark L. Van Meir, Erwin G. Scarpace, Lisa Laird, Peter W. Weinstein, John N. Lander, Eric S. Gabrie, Stacey Getz, Gad Meyerson, Matthew Chin, Lynda Barnholtz-Sloan, Jill S. Verhaak, Roel G. W. TI Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution SO GENOME RESEARCH LA English DT Article ID CIRCULAR BINARY SEGMENTATION; COPY-NUMBER; CLONAL EVOLUTION; INTRATUMOR HETEROGENEITY; MALIGNANT GLIOMAS; TP53 MUTATIONS; BREAST CANCERS; DNA; CELLS; LEUKEMIA AB Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence similar to 7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. C1 [Kim, Hoon; Zheng, Siyuan; Amini, Seyed S.; Weinstein, John N.; Verhaak, Roel G. W.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Kim, Hoon; Zheng, Siyuan; Muller, Florian; Hu, Jian; Weinstein, John N.; Chin, Lynda; Verhaak, Roel G. W.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Virk, Selene M.; Sloan, Andrew E.; Cohen, Mark L.; Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Mikkelsen, Tom; Scarpace, Lisa] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. [Mikkelsen, Tom; Scarpace, Lisa] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA. [Brat, Daniel J.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Grimsby, Jonna; Sougnez, Carrie; Lander, Eric S.; Gabrie, Stacey; Getz, Gad; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Sloan, Andrew E.] Case Western Reserve Sch Med, Univ Hosp Case Med Ctr, Brain Tumor & Neurooncol Ctr, Dept Neurosurg, Cleveland, OH 44706 USA. [Cohen, Mark L.] Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH 44106 USA. [Van Meir, Erwin G.] Emory Univ, Winship Canc Inst, Dept Neurosurg & Hematol & Med Oncol, Atlanta, GA 30322 USA. [Van Meir, Erwin G.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Laird, Peter W.] Van Andel Res Inst, Ctr Epigenet, Grand Rapids, MI 49503 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Verhaak, RGW (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. EM rverhaak@mdanderson.org FU NCI [P50 CA127001, P50 CA083639-12, P01 CA085878, R01 CA190121, CA016672]; Cancer Prevention & Research Institute of Texas (CPRIT) [R140606]; University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center; TCGA [28xS100]; MD Anderson Genome Data Analysis Center [CA143883]; H.A. and Mary K. Chapman Foundation; Michael and Susan Dell Foundation (honoring Lorraine Dell); Odyssey Program; Theodore N. Law Endowment for Scientific Achievement at The University of Texas MD Anderson Cancer Center; [R01 CA163722]; [HHSN261201000057C] FX We thank all members of TCGA GBM working group, Patricia S. Fox for assistance in survival analysis, and Lee Ann Chastain for assistance in manuscript editing. The results published here are in whole or part based upon data generated by The Cancer Genome Atlas project established by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) of the National Institutes of Health. Information about TCGA and the investigators and institutions that constitute the TCGA research network can be found at http://cancergenome.nih.gov. This work is supported by grants from the NCI, grant numbers P50 CA127001, P50 CA083639-12, P01 CA085878, R01 CA190121, Cancer Prevention & Research Institute of Texas (CPRIT) grant number R140606, and the University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center to R.G.W.V.; grant number R01 CA163722 and TCGA contract number 28xS100 to E.G.V.M.; grant number CA143883 (MD Anderson Genome Data Analysis Center) to J.N.W.; and contract number HHSN261201000057C for A.E.S., M.L.C., and J.S.B. The MD Anderson Sequencing and Microarray Facility is funded by NCI Grant CA016672. This work is also supported by generous funding from the H.A. and Mary K. Chapman Foundation and the Michael and Susan Dell Foundation (honoring Lorraine Dell) to J.N.W. H.K. is supported in part by the Odyssey Program and the Theodore N. Law Endowment for Scientific Achievement at The University of Texas MD Anderson Cancer Center. NR 54 TC 39 Z9 41 U1 3 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD MAR PY 2015 VL 25 IS 3 BP 316 EP 327 DI 10.1101/gr.180612.114 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CC7DA UT WOS:000350526700002 PM 25650244 ER PT J AU Dorman, C Wong, M Khan, A AF Dorman, Christina Wong, Mark Khan, Aazib TI Cholestatic Hepatitis From Prolonged Kratom Use: A Case Report SO HEPATOLOGY LA English DT Article C1 [Dorman, Christina; Wong, Mark] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Dorman, Christina; Wong, Mark] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wong, Mark] Audie L Murphy VA Hosp, San Antonio, TX 78229 USA. [Wong, Mark] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Khan, Aazib] Univ Texas Hlth Sci Ctr San Antonio, Internal Med, San Antonio, TX 78229 USA. RP Dorman, C (reprint author), 4114 Med Dr,Apt 19205, San Antonio, TX 78229 USA. EM christina.b.dorman@gmail.com NR 4 TC 5 Z9 5 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD MAR PY 2015 VL 61 IS 3 BP 1086 EP 1087 DI 10.1002/hep.27612 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CC2BS UT WOS:000350150300039 PM 25418457 ER PT J AU Cheever, TR Berkley, D Braun, S Brown, RH Byrne, BJ Chamberlain, JS Cwik, V Duan, DS Federoff, HJ High, KA Kaspar, BK Klinger, KW Larkindale, J Lincecum, J Mavilio, F McDonald, CL McLaughlin, J McLeod, BW Mendell, JR Nuckolls, G Stedman, HH Tagle, DA Vandenberghe, LH Wang, H Wernett, PJ Wilson, JM Porter, JD Gubitz, AK AF Cheever, Thomas R. Berkley, Dale Braun, Serge Brown, Robert H. Byrne, Barry J. Chamberlain, Jeffrey S. Cwik, Valerie Duan, Dongsheng Federoff, Howard J. High, Katherine A. Kaspar, Brian K. Klinger, Katherine W. Larkindale, Jane Lincecum, John Mavilio, Fulvio McDonald, Cheryl L. McLaughlin, James McLeod, Bonnie Weiss Mendell, Jerry R. Nuckolls, Glen Stedman, Hansell H. Tagle, Danilo A. Vandenberghe, Luk H. Wang, Hao Wernett, Pamela J. Wilson, James M. Porter, John D. Gubitz, Amelie K. TI Perspectives on Best Practices for Gene Therapy Programs SO HUMAN GENE THERAPY LA English DT Article AB With recent successes in gene therapy trials for hemophilia and retinal diseases, the promise and prospects for gene therapy are once again garnering significant attention. To build on this momentum, the National Institute of Neurological Disorders and Stroke and the Muscular Dystrophy Association jointly hosted a workshop in April 2014 on "Best Practices for Gene Therapy Programs," with a focus on neuromuscular disorders. Workshop participants included researchers from academia and industry as well as representatives from the regulatory, legal, and patient advocacy sectors to cover the gamut from preclinical optimization to intellectual property concerns and regulatory approval. The workshop focused on three key issues in the field: (1) establishing adequate scientific premise for clinical trials in gene therapy, (2) addressing regulatory process issues, and (3) intellectual property and commercialization issues as they relate to gene therapy. The outcomes from the discussions at this workshop are intended to provide guidance for researchers and funders in the gene therapy field. C1 [Cheever, Thomas R.; Nuckolls, Glen; Wang, Hao; Wernett, Pamela J.; Porter, John D.; Gubitz, Amelie K.] NINDS, NIH, Bethesda, MD 20892 USA. [Berkley, Dale] NIH, Off Gen Counsel, Bethesda, MD 20892 USA. [Braun, Serge] Assoc Francaise Myopathies, F-91002 Evry, France. [Brown, Robert H.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Byrne, Barry J.] Univ Florida, Sch Med, Dept Pediat, Gainesville, FL 32610 USA. [Chamberlain, Jeffrey S.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Cwik, Valerie] Muscular Dystrophy Assoc, Tucson, AZ 85718 USA. [Duan, Dongsheng] Univ Missouri, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA. [Federoff, Howard J.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. [High, Katherine A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [High, Katherine A.] Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. [High, Katherine A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kaspar, Brian K.; Mendell, Jerry R.] Nationwide Childrens Hosp, Res Inst, Ctr Gene Therapy, Columbus, OH 43205 USA. [Klinger, Katherine W.] Genzyme Corp, Framingham, MA 01701 USA. [Larkindale, Jane] NMD Consulting, Tucson, AZ 85750 USA. [Lincecum, John] Amyotroph Lateral Sclerosis Therapy Dev Inst, Cambridge, MA 02139 USA. [Mavilio, Fulvio] Genethon, F-91002 Evry, France. [McDonald, Cheryl L.] NHLBI, NIH, Bethesda, MD 20892 USA. [McLaughlin, James] Voyager Therapeut, Cambridge, MA 02139 USA. [McLeod, Bonnie Weiss] Cooley LLP, Washington, DC 20001 USA. [Stedman, Hansell H.] Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Tagle, Danilo A.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Vandenberghe, Luk H.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Vandenberghe, Luk H.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Wilson, James M.] Univ Penn, Gene Therapy Program, Philadelphia, PA 19104 USA. RP Gubitz, AK (reprint author), NINDS, NIH, Room 2154,6001 Execut Blvd, Bethesda, MD 20892 USA. EM gubitza@ninds.nih.gov RI Kaspar, Brian/E-3349-2011; Wilson, James/F-9220-2011; OI Wilson, James/0000-0002-9630-3131; Mavilio, Fulvio/0000-0003-0459-4320 FU MDA; NINDS FX We would like to thank Wilson Bryan and Mercedes Serabian (CBER/FDA), and Marco Passini (Genzyme, a Sanofi Company) for their participation in the workshop. We would also like to thank Paul Muhlrad, formerly of the MDA, for his help with early stages of organizing the workshop. This workshop was supported by the MDA and NINDS. NR 4 TC 3 Z9 4 U1 0 U2 9 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 MAR 1 PY 2015 VL 26 IS 3 BP 127 EP 133 DI 10.1089/hum.2014.147 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CD4MV UT WOS:000351058000001 PM 25654329 ER PT J AU Jasenosky, LD Scriba, TJ Hanekom, WA Goldfeld, AE AF Jasenosky, Luke D. Scriba, Thomas J. Hanekom, Willem A. Goldfeld, Anne E. TI T cells and adaptive immunity to Mycobacterium tuberculosis in humans SO IMMUNOLOGICAL REVIEWS LA English DT Review DE TB; CD4(+); CD8(+); IL-10-producing immunosuppressive and Treg cells; Th1 and Th17 cells; HIV co-infection ID ACTIVE PULMONARY TUBERCULOSIS; CALMETTE-GUERIN VACCINATION; RECONSTITUTION INFLAMMATORY SYNDROME; LATENTLY INFECTED INDIVIDUALS; SKIN-TEST RESPONSE; CD8(+) T; ANTIRETROVIRAL THERAPY; INTERFERON-GAMMA; IFN-GAMMA; POLYFUNCTIONAL CD4(+) AB The adaptive immune response mediated by T cells is critical for control of Mycobacterium tuberculosis (M.tuberculosis) infection in humans. However, the M.tuberculosis antigens and host T-cell responses that are required for an effective adaptive immune response to M.tuberculosis infection are yet to be defined. Here, we review recent findings on CD4(+) and CD8(+) T-cell responses to M.tuberculosis infection and examine the roles of distinct M.tuberculosis-specific T-cell subsets in control of de novo and latent M.tuberculosis infection, and in the evolution of T-cell immunity to M.tuberculosis in response to tuberculosis treatment. In addition, we discuss recent studies that elucidate aspects of M.tuberculosis-specific adaptive immunity during human immunodeficiency virus co-infection and summarize recent findings from vaccine trials that provide insight into effective adaptive immune responses to M.tuberculosis infection. C1 [Jasenosky, Luke D.; Goldfeld, Anne E.] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Scriba, Thomas J.; Hanekom, Willem A.] Univ Cape Town, South African TB Vaccine Initiat, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Scriba, Thomas J.; Hanekom, Willem A.] Univ Cape Town, Sch Child & Adolescent Hlth, ZA-7925 Cape Town, South Africa. [Hanekom, Willem A.] Bill & Melinda Gates Fdn, Seattle, WA USA. RP Goldfeld, AE (reprint author), Childrens Hosp, Program Cellular & Mol Med, 200 Longwood Ave, Boston, MA 02115 USA. EM anne.goldfeld@childrens.harvard.edu NR 210 TC 38 Z9 40 U1 4 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD MAR PY 2015 VL 264 IS 1 SI SI BP 74 EP 87 DI 10.1111/imr.12274 PG 14 WC Immunology SC Immunology GA CC2HX UT WOS:000350167200006 PM 25703553 ER PT J AU Foley, OW Rauh-Hain, JA Clemmer, J Clark, RM Hall, T Diver, EJ Schorge, JO del Carmen, MG AF Foley, Olivia W. Rauh-Hain, J. Alejandro Clemmer, Joel Clark, Rachel M. Hall, Tracilyn Diver, Elisabeth J. Schorge, John O. del Carmen, Marcela G. TI Trends in the Treatment of Uterine Leiomyosarcoma in the Medicare Population SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Uterine leiomyosarcoma; Chemotherapy; Radiotherapy; Survival ID GYNECOLOGIC-ONCOLOGY-GROUP; PROGNOSTIC-FACTORS; SARCOMAS; UTERUS; STAGE; CHEMOTHERAPY; VALIDATION; IMPACT AB Objective: Uterine leiomyosarcoma (LMS) is a relatively rare malignancy that is associated with a poor prognosis. The rarity of LMS has led to a lack of consensus regarding appropriate treatment. The goal of this study was to identify the role that chemotherapy and radiotherapy have played in the treatment of uterine LMS in the United States as well as the effectiveness of adjuvant treatment. Materials/Methods: We used the SEER (Surveillance, Epidemiology, and End Results)Medicare database to gather information on uterine LMS patients older than the age of 66 years diagnosed between 1992 and 2009. Basic demographic and clinical characteristics were collected. A logistic regression model analysis was performed to determine predictors of treatment. Cox proportional hazards models were used to identify clinical parameters and treatment strategies associated with survival differences. Results: Our final study group included 230 patients. We found that the rate of use of chemotherapy and radiotherapy in the treatment of patients with uterine LMS increased over the period investigated. However, we identified no significant survival advantage associated with either mode of therapy. The strongest predictor of survival was stage at diagnosis. The logistic regression model analysis revealed that age at diagnosis, treatment year, stage, and underlying health status were all independent predictors of chemotherapy. Age at diagnosis was also a predictor of radiation therapy. Conclusions: The increasing rates of chemotherapy and radiotherapy use in this population seem to be unfounded given the lack of survival benefit. Further investigation into alternative treatment regimens is merited. The prognostic significance of stage at diagnosis indicates the importance of improving early detection of uterine LMS. C1 [Foley, Olivia W.; Rauh-Hain, J. Alejandro; Clemmer, Joel; Clark, Rachel M.; Hall, Tracilyn; Diver, Elisabeth J.; 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, Div Gynecol Oncol, Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org FU Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital FX Supported by the Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital. NR 25 TC 4 Z9 4 U1 0 U2 5 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 MAR PY 2015 VL 25 IS 3 BP 453 EP 458 DI 10.1097/IGC.0000000000000372 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CC1SM UT WOS:000350123800016 PM 25628107 ER PT J AU Geary, S Selvi, F Chuang, SK August, M AF Geary, S. Selvi, F. Chuang, S. -K. August, M. TI Identifying dental panoramic radiograph features for the screening of low bone mass in postmenopausal women SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE osteoporosis; postmenopausal; menopause; panoramic; radiography ID MINERAL DENSITY; HIP-FRACTURES; RADIOMORPHOMETRIC INDEXES; OSTEOPOROTIC FRACTURES; RISK; STATEMENT; DIAGNOSIS; AGE AB A retrospective cohort study was performed to evaluate the use of panoramic radiographs as a screening tool for low bone mass in postmenopausal women. Female subjects aged >= 50 years were included. The predictor variables were gonial angle, antegonial angle, mandibular cortical bone integrity, periodontal disease status, and number of remaining teeth. The primary outcome variable was bone mineral density status. Descriptive and logistic regression statistics were computed; P < 0.05 was considered significant. The sample was composed of 273 subjects, aged 50-89 years. Visual assessment of mandibular cortical bone integrity demonstrated a statistically significant correlation with low bone mass diagnosis on univariate logistic regression (P = 0.019), but lost significance on multivariate analysis with age, body mass index, and number of remaining teeth (P = 0.6). A visual estimation of the mandibular cortical bone integrity from panoramic radiographs may be useful for identifying postmenopausal women at high risk for osteoporosis. C1 [Geary, S.; Chuang, S. -K.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Selvi, F.] Istanbul Univ, Dept Oral & Maxillofacial Surg, Fac Dent, Istanbul, Turkey. [August, M.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP August, M (reprint author), Massachusetts Gen Hosp, Oral & Maxillofacial Surg, 15 Parkman St, Boston, MA 02114 USA. EM Maugust@partners.org FU Department of Oral and Maxillofacial Surgery Education and Research Fund; Harvard Medical School Scholars in Medicine Office FX This study was funded by the Department of Oral and Maxillofacial Surgery Education and Research Fund and Harvard Medical School Scholars in Medicine Office. NR 22 TC 0 Z9 0 U1 4 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 EI 1399-0020 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD MAR PY 2015 VL 44 IS 3 BP 395 EP 399 DI 10.1016/j.ijom.2014.11.008 PG 5 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA CC7DJ UT WOS:000350527600016 PM 25480009 ER PT J AU Dryden-Peterson, S Lockman, S Zash, R Lei, QH Chen, JY Souda, S Petlo, C Dintwa, E Lebelonyane, R Mmalane, M Shapiro, RL AF Dryden-Peterson, Scott Lockman, Shahin Zash, Rebecca Lei, Quonhong Chen, Jennifer Y. Souda, Sajini Petlo, Chipo Dintwa, Eldah Lebelonyane, Refeletswe Mmalane, Mompati Shapiro, Roger L. TI Initial Programmatic Implementation of WHO Option B in Botswana Associated With Increased Projected MTCT SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE PMTCT; Option B; implementation science; sub-Saharan Africa; ART initiation; HIV-1 ID MOTHER-TO-CHILD; ACTIVE ANTIRETROVIRAL THERAPY; HIV TRANSMISSION; DOUBLE-BLIND; ZIDOVUDINE; EFFICACY; TRIAL; PREVENTION; LAMIVUDINE; REGIMENS AB Botswana was one of the first African countries to transition from WHO Option A to Option B for prevention of mother-to-child HIV transmission (MTCT). We evaluated the impact of this transition on projected MTCT risk through review of 10,681 obstetric records of HIV-infected women delivering at 6 maternity wards. Compared with Option A, women receiving antenatal care under Option B were more likely to receive combination antiretroviral therapy (ART), adjusted odds ratio (aOR): 2.59 (95% confidence interval: 2.25 to 2.98), but they were also more likely to receive no antenatal antiretrovirals, aOR: 2.10 (95% confidence interval: 1.74 to 2.53). Consequently, initial implementation of Option B was associated with increased projected MTCT at 6 months of age, 3.79% under Option A and 4.69% under Option B (P < 0.001). Successful implementation of Option B or B+ may require that ART can be initiated within antenatal clinics, and novel strategies to remove barriers to rapid ART initiation. C1 [Dryden-Peterson, Scott; Lockman, Shahin] Brigham & Womens Hosp, Div Infect Dis, Dept Med, Boston, MA 02115 USA. [Dryden-Peterson, Scott; Lockman, Shahin; Zash, Rebecca; Mmalane, Mompati; Shapiro, Roger L.] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Dryden-Peterson, Scott; Lockman, Shahin; Shapiro, Roger L.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Zash, Rebecca; Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Dept Med, Div Infect Dis, Boston, MA 02215 USA. [Lei, Quonhong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Chen, Jennifer Y.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Souda, Sajini] Univ Botswana, Dept Pathol, Fac Hlth Sci, Gaborone, Botswana. [Petlo, Chipo; Dintwa, Eldah; Lebelonyane, Refeletswe] Minist Hlth, Dept HIV AIDS Prevent & Care, Gaborone, Botswana. RP Dryden-Peterson, S (reprint author), Brigham & Womens Hosp, Div Infect Dis, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM scott_peterson@post.harvard.edu FU Centers for Disease Control and Prevention [U2GPS000941]; National Institutes of Health [3R01HD044391-06S1, 5K23AI091434, 3R01HD0443910-6S1, K23AI091434] FX Supported by research grants from the Centers for Disease Control and Prevention (U2GPS000941) and the National Institutes of Health (3R01HD044391-06S1, 5K23AI091434).; Supported by grants from the National Institutes of Health (3R01HD0443910-6S1, K23AI091434). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 5 Z9 5 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2015 VL 68 IS 3 BP 245 EP 249 DI 10.1097/QAI.0000000000000482 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CC3JZ UT WOS:000350245400007 PM 25501611 ER PT J AU Drain, PK Losina, E Coleman, SM Giddy, J Ross, D Katz, JN Bassett, IV AF Drain, Paul K. Losina, Elena Coleman, Sharon M. Giddy, Janet Ross, Douglas Katz, Jeffrey N. Bassett, Ingrid V. TI Value of Urine Lipoarabinomannan Grade and Second Test for Optimizing Clinic-Based Screening for HIV-Associated Pulmonary Tuberculosis SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE tuberculosis; HIV; AIDS; lipoarabinomannan; urine; screening; South Africa ID DIAGNOSTIC-ACCURACY; ANTIRETROVIRAL THERAPY; HOSPITALIZED-PATIENTS; SPUTUM SAMPLES; SOUTH-AFRICA; LAM-ELISA; ASSAY; PREVALENCE; SETTINGS; ANTIGEN AB Background:We assessed the role of urine lipoarabinomannan (LAM) grade and a second LAM test for HIV-associated pulmonary tuberculosis (TB) screening in outpatient clinics in South Africa.Methods:We enrolled newly diagnosed HIV-infected adults (18 years) at 4 clinics, excluding those on TB therapy. Participants provided sputum for acid-fast bacilli (AFB) microscopy and culture. Nurses conducted 2 rapid urine LAM tests at the point-of-care and graded positive results from low (faint) to high (5+). Culture-confirmed pulmonary TB was the gold standard. We used area under receiver operating curves (AUROC) to compare screening strategies.Results:Among 320 HIV-infected adults, median CD4 was 248 cells per cubic millimeter (interquartile range, 107-379/mm(3)); 54 (17%) were TB culture positive. Fifty-two (16%) of all participants were LAM positive by either test; correlation between LAM tests was high. Among 10 faint positive results, 2 (20%) had culture-positive TB. Using 1+ LAM grade as positive, 1 LAM test had sensitivity of 41% [95% confidence interval (CI): 28% to 55%] and specificity of 92% (95% CI: 88% to 95%). A 2 LAM test strategy had a sensitivity of 43% (95% CI: 29% to 57%). One LAM test 1+ grade (AUROC = 0.66; 95% CI: 0.60 to 0.73) was significantly better than sputum AFB alone. The optimal strategy was sequentially performing 1 LAM test followed by sputum AFB if LAM grade <1+ (AUROC = 0.70; 95% CI: 0.63 to 0.77), which had sensitivity of 48% (95% CI: 34% to 62%) and specificity of 91% (95% CI: 87% to 94%).Conclusions:In this clinic-based study, faint line was a false-positive second urine LAM test added no value, and an optimal screening strategy was 1 LAM test followed by sputum AFB microscopy for urine LAM-negative people. C1 [Drain, Paul K.; Losina, Elena; Bassett, Ingrid V.] Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Drain, Paul K.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. [Drain, Paul K.; Bassett, Ingrid V.] Harvard Univ, Brigham & Womens Hosp, Div Infect Dis, Dept Med,Med Sch, Boston, MA 02115 USA. [Losina, Elena] Massachusetts Gen Hosp, Dept Med, Gen Internal Med, Boston, MA 02114 USA. [Losina, Elena; Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Dept Orthoped Surg, Sch Med, Boston, MA 02115 USA. [Coleman, Sharon M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Giddy, Janet] McCord Hosp, Dept Med, Durban, South Africa. [Ross, Douglas] St Marys Hosp, Dept Med, Durban, South Africa. RP Drain, PK (reprint author), Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM pdrain@partners.org FU Harvard Global Health Institute; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988]; Infectious Disease Society of America Education and Research Foundation (IDSA ERF); National Foundation for Infectious Diseases (NFID), Massachusetts General Hospital Executive Committee on Research, The Program in AIDS Clinical Research Training Grant [T32 AI007433]; National Institute of Mental Health [R01 MH090326]; National Institute of Allergy and Infectious Diseases [K23 AI108293]; Harvard University Center for AIDS Research [P30 AI060354]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24 AR057827]; National Center for Research Resources (Harvard Catalyst) [UL1 RR 025758]; Claflin Distinguished Scholar Award FX Supported by the Harvard Global Health Institute, the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988), the Infectious Disease Society of America Education and Research Foundation (IDSA ERF) and National Foundation for Infectious Diseases (NFID), Massachusetts General Hospital Executive Committee on Research, The Program in AIDS Clinical Research Training Grant (T32 AI007433) (P.K.D.); the National Institute of Mental Health R01 MH090326 (I.V.B.); the National Institute of Allergy and Infectious Diseases K23 AI108293 (P.K.D.); the Harvard University Center for AIDS Research P30 AI060354; the National Institute of Arthritis and Musculoskeletal and Skin Diseases K24 AR057827 (E.L.); the National Center for Research Resources (the Harvard Catalyst UL1 RR 025758); and the Claflin Distinguished Scholar Award (I.V.B.). NR 30 TC 8 Z9 8 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2015 VL 68 IS 3 BP 274 EP 280 DI 10.1097/QAI.0000000000000436 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CC3JZ UT WOS:000350245400011 PM 25415288 ER PT J AU Mimiaga, MJ O'Cleirigh, C Biello, KB Robertson, AM Safren, SA Coates, TJ Koblin, BA Chesney, MA Donnell, DJ Stall, RD Mayer, KH AF Mimiaga, Matthew J. O'Cleirigh, Conall Biello, Katie B. Robertson, Angela M. Safren, Steven A. Coates, Thomas J. Koblin, Beryl A. Chesney, Margaret A. Donnell, Deborah J. Stall, Ron D. Mayer, Kenneth H. TI The Effect of Psychosocial Syndemic Production on 4-Year HIV Incidence and Risk Behavior in a Large Cohort of Sexually Active Men Who Have Sex With Men SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; men who have sex with men; psychosocial conditions; prevention of HIV; sexual behaviors ID MULTICENTER AIDS COHORT; BASE-LINE DATA; HEALTH-PROBLEMS; UNITED-STATES; SUBSTANCE USE; YOUNG MEN; EXPLORE; INTERVENTION; GAY; ASSOCIATIONS AB Background:Cross-sectional studies have suggested that co-occurring epidemics or syndemics of psychosocial health problems may accelerate HIV transmission among men who have sex with men (MSM) in the United States. We aimed to assess how 5 syndemic conditions (depressive symptoms, heavy alcohol use, stimulant use, polydrug use, and childhood sexual abuse) affected HIV incidence and sexual risk behavior over time.Methods:Eligible men in a large prospective cohort of sexually active HIV-uninfected MSM completed HIV testing and behavioral surveys at baseline and every 6 months for 48 months. We examined interrelationships between psychosocial problems and whether these interactions increased the odds of HIV risk behaviors and risk of seroconversion over study follow-up.Results:Among 4295 men, prevalence of psychosocial conditions was substantial at baseline and was positively associated with each other. We identified a statistically significant positive dose-response relationship between numbers of syndemic conditions and HIV seroconversion for all comparisons (with the greatest hazard among those with 4-5 conditions, adjusted hazard ratio = 8.69; 95% confidence interval: 4.78 to 15.44). The number of syndemic conditions also predicted increased HIV-related risk behaviors over time, which mediated the syndemic-HIV seroconversion association.Conclusions:The accumulation of syndemic psychosocial problems predicted HIV-related sexual risk behaviors and seroconversion in a large sample of US MSM. Given the high prevalence of syndemic conditions among MSM and the moderate effect sizes attained by traditional brief behavioral interventions to date, the HIV prevention agenda requires a shift toward improved assessment of psychosocial comorbidities and stronger integration with mental health and substance abuse treatment services. C1 [Mimiaga, Matthew J.; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Dept Psychiat, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mimiaga, Matthew J.; Biello, Katie B.; Robertson, Angela M.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02114 USA. [Mimiaga, Matthew J.; O'Cleirigh, Conall; Biello, Katie B.; Robertson, Angela M.; Safren, Steven A.; Mayer, Kenneth H.] Fenway Inst, Fenway Hlth, Boston, MA USA. [Coates, Thomas J.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr World Hlth, Los Angeles, CA 90095 USA. [Koblin, Beryl A.] New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10021 USA. [Chesney, Margaret A.] Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. [Donnell, Deborah J.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Stall, Ron D.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Mayer, Kenneth H.] Harvard Univ, Dept Infect Dis, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02114 USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Dept Psychiat, Behav Med Serv, Med Sch,Massachusetts Gen Hosp, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mmimiaga@mgh.harvard.edu OI Bazzi, Angela/0000-0001-6828-1919; Donnell, Deborah/0000-0002-0587-7480 FU HIV Network for Prevention Trials; US National Institute of Allergy and Infectious Diseases; National Institute on Alcohol Abuse and Alcoholism [N01 AI35176]; Abt Associates Inc; Fred Hutchinson Cancer Research Center [N01 AI45200]; Denver Department of Health and Hospitals; Fenway Community Health Center; Howard Brown Health Center; New York Blood Center; Public Health Foundation Inc; University of Washington; HIV Prevention Trials Network; National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institute of Mental Health; Office of AIDS Research; Family Health International [5 U01 AI46749]; National Institute of Mental Health, NIH [R01 MH095624-01]; [U01 AI48040]; [U01 AI48016]; [U01 AI47981]; [U01 AI47995] FX Supported by the HIV Network for Prevention Trials and sponsored by the US National Institute of Allergy and Infectious Diseases and the National Institute on Alcohol Abuse and Alcoholism through contract N01 AI35176 with Abt Associates Inc; contract N01 AI45200 with the Fred Hutchinson Cancer Research Center; and subcontracts with the Denver Department of Health and Hospitals, the Fenway Community Health Center, the Howard Brown Health Center, the New York Blood Center, the Public Health Foundation Inc, and the University of Washington. In addition, this work was supported by the HIV Prevention Trials Network and sponsored by the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the National Institute of Mental Health, and the Office of AIDS Research through a cooperative agreement with Family Health International (cooperative agreement 5 U01 AI46749) with a subsequent subcontract to Abt Associates Inc with subcontracts to the Howard Brown Health Center and the Denver Department of Health and Hospitals; cooperative agreement U01 AI48040 to the Fenway Community Health Center, cooperative agreement U01 AI48016 to Columbia University (including a subagreement with the New York Blood Center), cooperative agreement U01 AI47981 to the University of Washington, cooperative agreement U01 AI47995 to the University of California, San Francisco. The time of Dr C.O'C. on this article was supported in part by R01 MH095624-01 Integrated Trauma and HIV Prevention Treatment for MSM with Childhood Sexual Abuse Histories (PI: C.O'C.) awarded by the National Institute of Mental Health, NIH. NR 30 TC 28 Z9 29 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2015 VL 68 IS 3 BP 329 EP 336 DI 10.1097/QAI.0000000000000475 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CC3JZ UT WOS:000350245400019 PM 25501609 ER PT J AU Pietrzak, RH Lim, YY Neumeister, A Ames, D Ellis, KA Harrington, K Lautenschlager, NT Restrepo, C Martins, RN Masters, CL Villemagne, VL Rowe, CC Maruff, P AF Pietrzak, Robert H. Lim, Yen Ying Neumeister, Alexander Ames, David Ellis, Kathryn A. Harrington, Karra Lautenschlager, Nicola T. Restrepo, Carolina Martins, Ralph N. Masters, Colin L. Villemagne, Victor L. Rowe, Christopher C. Maruff, Paul CA Australian Imaging Biomarkers & Li TI Amyloid-beta, Anxiety, and Cognitive Decline in Preclinical Alzheimer Disease A Multicenter, Prospective Cohort Study SO JAMA PSYCHIATRY LA English DT Article ID HEALTHY OLDER-ADULTS; RANDOMIZED-CONTROLLED-TRIAL; LATE-LIFE ANXIETY; MEMORY DECLINE; NEUROPSYCHIATRIC SYMPTOMS; CLINICAL-TRIAL; DOUBLE-BLIND; STYLE AIBL; IMPAIRMENT; DEPRESSION AB IMPORTANCE Alzheimer disease (AD) is now known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. Although the presence of abnormal levels of amyloid-beta (A beta) is associated with higher rates of progression to clinically classified mild cognitive impairment or dementia, little research has evaluated potentially modifiable moderators of A beta-related cognitive decline, such as anxiety and depressive symptoms. OBJECTIVE To evaluate the association between A beta status and cognitive changes, and the role of anxiety and depressive symptoms in moderating A beta-related cognitive changes in the preclinical phase of AD. DESIGN, SETTING, AND PARTICIPANTS In this multicenter, prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments, we studied 333 healthy, older adults at hospital-based research clinics. MAIN OUTCOMES AND MEASURES Carbon 11-labeled Pittsburgh Compound B (PiB)-, florbetapir F 18-, or flutemetamol F 18-derived measures of A beta, Hospital Anxiety and Depression Scale scores, and comprehensive neuropsychological evaluation that yielded measures of global cognition, verbal memory, visual memory, attention, language, executive function, and visuospatial ability. RESULTS A positive A beta (A beta+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function, and elevated anxiety symptoms moderated these associations. Compared with the A beta+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the A beta+, high-anxiety group, with Cohen d values of 0.78 (95% CI, 0.33-1.23) for global cognition, 0.54 (95% CI, 0.10-0.98) for verbal memory, 0.51 (95% CI, 0.07-0.96) for language, and 0.39 (95% CI, 0.05-0.83) for executive function. These effects were independent of age, educational level, IQ, APOE genotype, subjective memory complaints, vascular risk factors, and depressive symptoms; furthermore, depressive symptoms and subjective memory complaints did not moderate the association between A beta and cognitive decline. CONCLUSIONS AND RELEVANCE These results provide additional support for the deleterious effect of elevated A beta levels on cognitive function in preclinical AD. They further suggest that elevated anxiety symptoms moderate the effect of A beta on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. Given that there is currently no standard antiamyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD. C1 [Pietrzak, Robert H.] US Dept Vet Affairs, Vet Affairs Connecticut Healthcare Syst, Clin Neurosci Div, West Haven, CT 06516 USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Lim, Yen Ying; Ellis, Kathryn A.; Harrington, Karra; Restrepo, Carolina; Masters, Colin L.; Villemagne, Victor L.; Maruff, Paul] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia. [Lim, Yen Ying] Brown Univ, Warren Alpert Sch Med, Dept Neurol, Providence, RI 02912 USA. [Neumeister, Alexander] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Neumeister, Alexander] NYU, Sch Med, Dept Radiol, New York, NY USA. [Ames, David; Ellis, Kathryn A.; Lautenschlager, Nicola T.] Univ Melbourne, St Vincents Hlth, Dept Psychiat, Acad Unit Psychiat Old Age, Kew, Vic, Australia. [Ames, David; Ellis, Kathryn A.; Lautenschlager, Nicola T.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia. [Ames, David; Ellis, Kathryn A.; Lautenschlager, Nicola T.] Univ Western Australia, Western Australia Ctr Hlth & Ageing, Perth, WA 6009, Australia. [Martins, Ralph N.] Edith Cowan Univ, Ctr Excellence Alzheimers Dis Res & Care, Sch Exercise Biomed & Hlth Sci, Perth, WA, Australia. [Villemagne, Victor L.; Rowe, Christopher C.] Austin Hlth, Dept Nucl Med, Heidelberg, Vic, Australia. [Villemagne, Victor L.; Rowe, Christopher C.] Austin Hlth, Ctr Positron Emiss Tomog, Heidelberg, Vic, Australia. [Villemagne, Victor L.; Rowe, Christopher C.] Univ Melbourne, Austin Hlth, Dept Med, Heidelberg, Vic, Australia. [Maruff, Paul] Cogstate Ltd, Melbourne, Vic, Australia. RP Pietrzak, RH (reprint author), US Dept Vet Affairs, Vet Affairs Connecticut Healthcare Syst, Clin Neurosci Div, 950 Campbell Ave,Mail Code 161E, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu RI Laws, Simon/C-2858-2014; OI Laws, Simon/0000-0002-4355-7082; Hone, Eugene/0000-0001-6708-3718 FU Commonwealth Scientific Industrial and Research Organization; Edith Cowan University; Mental Health Research Institute; National Ageing Research Institute; Austin Health; National Health and Medical Research Council; Dementia Collaborative Research Centres program; Science and Industry Endowment Fund; Cooperative Research Centre for Mental Health; Cogstate Ltd FX Funding for the Australian Imaging, Biomarkers, and Lifestyle Study was provided in part by the study partners (Commonwealth Scientific Industrial and Research Organization, Edith Cowan University, Mental Health Research Institute, National Ageing Research Institute, Austin Health, and Cogstate Ltd). The study also received support from the National Health and Medical Research Council and the Dementia Collaborative Research Centres program, as well as funding from the Science and Industry Endowment Fund and the Cooperative Research Centre for Mental Health. NR 51 TC 16 Z9 16 U1 3 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAR PY 2015 VL 72 IS 3 BP 284 EP 291 DI 10.1001/jamapsychiatry.2014.2476 PG 8 WC Psychiatry SC Psychiatry GA CC7UJ UT WOS:000350573600012 PM 25629787 ER PT J AU Blosnich, JR AF Blosnich, John R. TI Adverse Childhood Experiences and Military Service Reply SO JAMA PSYCHIATRY LA English DT Letter C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM john.blosnich@va.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAR PY 2015 VL 72 IS 3 BP 296 EP 297 PG 3 WC Psychiatry SC Psychiatry GA CC7UJ UT WOS:000350573600016 PM 25738693 ER PT J AU Fuzaylov, G Anderson, R Knittel, J Driscoll, DN AF Fuzaylov, Gennadiy Anderson, Richard Knittel, Justin Driscoll, Daniel N. TI Global Health: Burn Outreach Program SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID UKRAINE; SURGERY; MODEL; CARE AB The objective of this article is to outline the elements of an international burn care outreach program in a resource-constrained country. The program has grown from a collaborative effort with Ukrainian physicians and healthcare officials. With this collaboration, a multipronged approach has been developed to address the gaps in burn care as discovered by years of interaction with the medical community in Ukraine. Contact was initiated with the burn unit of a single municipal hospital in Lviv, Ukraine. Patients with burn injuries were screened and selected patients were comanaged over a 3-year period by American and Ukrainian physicians. This comanagement included repeated evaluation both by telemedicine conferencing as well as annual trips with physicians from Boston, Massachusetts, traveling to Ukraine to assess patients in an outreach clinic and perform surgical procedures. In our first trip in 2011 we assessed 22 patients and operated on 5. In 2012, 38 patients were evaluated and 12 had combined surgical intervention. In our 2013 trip, 63 patients were evaluated and we operated on 22 of these patients. Multiple clinical research projects related to burn prevention and improving perioperative care have been initiated, presented at national meetings, and submitted for publication in peer-reviewed journals. Our outreach program in Lviv, Ukraine, strives to improve overall burn care by a multilayered approach. These elements can serve as a possible template for additional international burn outreach plans as they can be customized for both large and small interventions. C1 [Fuzaylov, Gennadiy; Anderson, Richard; Knittel, Justin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Driscoll, Daniel N.] Shriners Hosp Crippled Children, Div Plast Surg, Dept Surg, Boston, MA USA. RP Fuzaylov, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. FU Ukrainian National Women League of America, United States; Doctors Collaborating to Help Children Corporation, United States; WonderWork, United States; Masimo Corporation, Shriners Hospitals for Children, Boston, MA, United States; Massachusetts General Hospital, Boston, MA, United States; AmeriCare Medical Supplies, United States; Rotary International FX This study has been funded by Ukrainian National Women League of America, United States, Doctors Collaborating to Help Children Corporation, United States, WonderWork, United States, Masimo Corporation, Shriners Hospitals for Children, Boston, MA, United States, Massachusetts General Hospital, Boston, MA, United States, AmeriCare Medical Supplies, United States, and Rotary International. NR 11 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD MAR-APR PY 2015 VL 36 IS 2 BP 306 EP 309 DI 10.1097/BCR.0000000000000074 PG 4 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA CC5JO UT WOS:000350395100026 PM 24823335 ER PT J AU Ibrahim, AE Goverman, J Sarhane, KA Donofrio, J Walker, TG Fagan, SP AF Ibrahim, Amir E. Goverman, Jeremy Sarhane, Karim A. Donofrio, Jill Walker, T. Gregory Fagan, Shawn P. TI The Emerging Role of Tissue Plasminogen Activator in the Management of Severe Frostbite SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID OPEN-LABEL; THERAPY; INJURY; AMPUTATION; EVALUATE; EFFICACY; DEXTRAN; SAFETY AB This article presents a small case series demonstrating clinical success with thrombolytic agents for severe frostbite injury to the lower extremities. The authors report three patients with severe frostbite injuries to their distal lower extremities who were managed with urgent interventional radiology and intra-arterial tissue plasminogen activator infusion according to a prespecified protocol. Limbs and digits were successfully salvaged and patients returned to normal activity within 2 weeks. Although further studies are needed, results of this study support a new approach in the management of frostbite: from conservative management and observation to urgent interventional radiology and possible tissue plasminogen activator infusion. A protocol for the management of such injuries is presented. C1 [Ibrahim, Amir E.; Goverman, Jeremy; Fagan, Shawn P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Burns,Dept Surg, Boston, MA 02114 USA. [Sarhane, Karim A.] Johns Hopkins Univ, Dept Plast & Reconstruct Surg, Baltimore, MD USA. [Donofrio, Jill] UNECOM Kent Hosp Emergency Med Program, Warwick, RI USA. [Walker, T. Gregory] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Goverman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Burns,Dept Surg, Boston, MA 02114 USA. NR 24 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD MAR-APR PY 2015 VL 36 IS 2 BP E62 EP E66 DI 10.1097/BCR.0000000000000135 PG 5 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA CC5JO UT WOS:000350395100009 PM 25687362 ER PT J AU Forghani, R Kim, HJ Wojtkiewicz, GR Bure, L Wu, Y Hayase, M Wei, Y Zheng, Y Moskowitz, MA Chen, JW AF Forghani, Reza Kim, Hyeon Ju Wojtkiewicz, Gregory R. Bure, Lionel Wu, Yue Hayase, Makoto Wei, Ying Zheng, Yi Moskowitz, Michael A. Chen, John W. TI Myeloperoxidase propagates damage and is a potential therapeutic target for subacute stroke SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE inflammation; ischemia; myeloperoxidase; stroke ID ISCHEMIC BRAIN-INJURY; CEREBRAL-ISCHEMIA; DIFFUSION; DEFICIENCY; MECHANISM; INFLAMMATION; ACTIVATION; INFARCTION; MORTALITY; RATS AB Few effective treatment options exist for stroke beyond the hyperacute period. Radical generation and myeloperoxidase (MPO) have been implicated in stroke. We investigated whether pharmacologic reduction or gene deletion of this highly oxidative enzyme reduces infarct propagation and improves outcome in the transient middle cerebral artery occlusion mouse model (MCAO). Mice were treated with 4-aminobenzoic acid hydrazide (ABAH), a specific irreversible MPO inhibitor. Three treatment regimens were used: (1) daily throughout the 21-day observational period, (2) during the acute stage (first 24 hours), or (3) during the subacute stage (daily starting on day 2). We found elevated MPO activity in ipsilateral brain 3 to 21 days after ischemia. 4-Aminobenzoic acid hydrazide reduced enzyme activity by 30% to 40% and final lesion volume by 60% (P < 0.01). The MPO-knockout (KO) mice subjected to MCAO also showed a similar reduction in the final lesion volume (P < 0.01). The ABAH treatment or MPO-KO mice also improved neurobehavioral outcome (P < 0.001) and survival (P=0.01), but ABAH had no additional beneficial effects in MPO-KO mice, confirming specificity of ABAH. Interestingly, inhibiting MPO activity during the subacute stage recapitulated most of the therapeutic benefit of continuous MPO inhibition, suggesting that MPO-targeted therapies could be useful when given after 24 hours of stroke onset. C1 [Forghani, Reza; Kim, Hyeon Ju; Wojtkiewicz, Gregory R.; Bure, Lionel; Wu, Yue; Chen, John W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02115 USA. [Forghani, Reza; Moskowitz, Michael A.; Chen, John W.] Harvard Univ, Div Neuroradiol, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02115 USA. [Hayase, Makoto; Wei, Ying; Zheng, Yi; Moskowitz, Michael A.] Harvard Univ, Stroke & Neurovasc Regulat Lab, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02115 USA. [Hayase, Makoto; Wei, Ying; Zheng, Yi; Moskowitz, Michael A.] Harvard Univ, Stroke & Neurovasc Regulat Lab, Dept Neurol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02115 USA. RP Chen, JW (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,5-210 Richard B Simches Res Bld, Boston, MA 02114 USA. EM jwchen@mgh.harvard.edu FU National Institute of Health [R01-NS070835, R01-NS072167]; Radiological Society of North America Research Fellow Grant FX This study was supported in part by the National Institute of Health (R01-NS070835 and R01-NS072167 to JWQ. RF received support from a Radiological Society of North America Research Fellow Grant. NR 42 TC 6 Z9 8 U1 1 U2 8 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 MAR PY 2015 VL 35 IS 3 BP 485 EP 493 DI 10.1038/jcbfm.2014.222 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CC5IZ UT WOS:000350393600018 PM 25515211 ER PT J AU Doyle, AE AF Doyle, Alysa E. TI Commentary: Insights from across diagnostic boundaries: ADHD in the RDoC era - a commentary on Scerif and Baker (2015) SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Editorial Material DE Attention-deficit; hyperactivity disorder; RDoC framework; shared risk mechanisms; child psychopathology; genetic studies ID DOMAIN CRITERIA RDOC AB Unbiased genomewide association studies of tens of thousands of individuals are transforming our understanding of the origins and structure of psychopathology across the lifespan. Together with findings from epidemiology and cognitive neuroscience, these recent molecular genetic studies underscore the importance of studying phenotypes across as well as within conventional psychiatric diagnoses in order to construct a more pathophysiologically grounded taxonomy from the bottom up. Such efforts, promoted by NIMH's Research Domain Criteria (RDoC) framework, are critical to developing more accurate models of the risk mechanisms that are shared and distinct across various psychopathologic outcomes. In turn, these models could reveal new treatment targets and early intervention opportunities. In their article in the 2015 JCPP Annual Research Review, Scerif and Baker remind us that bottom-up insights into psychiatric illness might also be gained by examining specific genetic disorders that often fall within the purview of pediatrics and neurology. These authors note high rates of symptoms of attention-deficit hyperactivity disorder (ADHD) in syndromes with known and often monogenic genetic causes (e.g. Fragile X) and suggest that studying the ADHD-like phenomena in these conditions may provide insight into ADHD itself. This commentary highlights themes from Scerif and Baker's review that overlap with the core tenets of RDoC and notes their significance for advancing our understanding of ADHD in the coming years. It concludes by suggesting ways in which further attention to the RDoC framework could also enhance Scerif and Baker's agenda. Read the full article at doi: C1 [Doyle, Alysa E.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Boston, MA 02114 USA. [Doyle, Alysa E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Sch Med, Boston, MA 02114 USA. [Doyle, Alysa E.] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. RP Doyle, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, 15 Parkman St, Boston, MA 02114 USA. EM doylea@helix.mgh.harvard.edu NR 9 TC 0 Z9 0 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD MAR PY 2015 VL 56 IS 3 SI SI BP 274 EP 277 DI 10.1111/jcpp.12401 PG 4 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CC4DX UT WOS:000350302100007 PM 25714738 ER PT J AU Walcott, BP Khanna, A Yanamadala, V Coumans, JV Peterfreund, RA AF Walcott, Brian P. Khanna, Arjun Yanamadala, Vijay Coumans, Jean-Valery Peterfreund, Robert A. TI Cost analysis of spinal and general anesthesia for the surgical treatment of lumbar spondylosis SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Cost; Discectomy; Herniated disc; Laminectomy; Lumbar spondylosis; Spinal anesthesia; Spinal stenosis ID PERIOPERATIVE OUTCOME VARIABLES; DEGENERATIVE SPONDYLOLISTHESIS; LAMINECTOMY SURGERY; DISC; STENOSIS AB Lumbar spine surgery is typically performed under general anesthesia, although spinal anesthesia can also be used. Given the prevalence of lumbar spine surgery, small differences in cost between the two anesthetic techniques have the potential to make a large impact on overall healthcare costs. We sought to perform a cost comparison analysis of spinal versus general anesthesia for lumbar spine operations. Following Institutional Review Board approval, a retrospective cohort study was performed from 2009-2012 on consecutive patients undergoing non-instrumented, elective lumbar spine surgery for spondylosis by a single surgeon. Each patient was evaluated for both types of anesthesia, with the decision for anesthetic method being made based on a combination of physical status, anatomical considerations, and ultimately a consensus agreement between patient, surgeon, and anesthesiologist. Patient demographics and clinical characteristics were compared between the two groups. Operating room costs were calculated whilst blinded to clinical outcomes and reported in percentage difference. General anesthesia (n = 319) and spinal anesthesia (n = 81) patients had significantly different median operative times of 175 +/- 39.08 and 158 +/- 32.75 minutes, respectively (p < 0.001, Mann-Whitney U test). Operating room costs were 10.33% higher for general anesthesia compared to spinal anesthesia (p = 0.003, Mann Whitney U test). Complications of spinal anesthesia included excessive movement (n = 1), failed spinal attempt (n = 3), intraoperative conversion to general anesthesia (n = 2), and a high spinal level (n = 1). In conclusion, spinal anesthesia can be performed safely in patients undergoing lumbar spine surgery. It has the potential to reduce operative times, costs, and possibly, complications. Further prospective evaluation will help to validate these findings. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.; Khanna, Arjun; Yanamadala, Vijay; Coumans, Jean-Valery] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Khanna, Arjun; Yanamadala, Vijay; Coumans, Jean-Valery; Peterfreund, Robert A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Peterfreund, Robert A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 20 TC 2 Z9 2 U1 2 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD MAR PY 2015 VL 22 IS 3 BP 539 EP 543 DI 10.1016/j.jocn.2014.08.024 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CC6YN UT WOS:000350515000020 PM 25510535 ER PT J AU Koffie, RM Stapleton, CJ Torok, CM Yoo, AJ Leslie-Mazwi, TM Codd, PJ AF Koffie, Robert M. Stapleton, Christopher J. Torok, Collin M. Yoo, Albert J. Leslie-Mazwi, Thabele M. Codd, Patrick J. TI Rapid growth of an infectious intracranial aneurysm with catastrophic intracranial hemorrhage SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Endovascular neurosurgery; Infectious intracranial aneurysm; Mycotic aneurysm; Subarachnoid hemorrhage; Vascular neurosurgery ID CEREBRAL MYCOTIC-ANEURYSMS AB Infectious intracranial aneurysms are rare vascular lesions that classically occur in patients with infective endocarditis. We present a 49-year-old man with altered mental status and headache with rapid growth and rupture of an infectious intracranial aneurysm with catastrophic intracranial hemorrhage, and review issues related to open neurosurgical and endovascular interventions. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Koffie, Robert M.; Stapleton, Christopher J.; Codd, Patrick J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Koffie, Robert M.; Stapleton, Christopher J.; Torok, Collin M.; Yoo, Albert J.; Leslie-Mazwi, Thabele M.; Codd, Patrick J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Stapleton, Christopher J.; Torok, Collin M.; Yoo, Albert J.; Leslie-Mazwi, Thabele M.] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Neuroradiol, Boston, MA 02114 USA. RP Stapleton, CJ (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White 502, Boston, MA 02114 USA. EM cstapleton@partners.org NR 6 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD MAR PY 2015 VL 22 IS 3 BP 603 EP 605 DI 10.1016/j.jocn.2014.09.007 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CC6YN UT WOS:000350515000036 PM 25455738 ER PT J AU Glass, NE Pinna, A Masi, A Rosman, AS Neihaus, D Okochi, S Saunders, JK Hatzaras, I Cohen, S Berman, R Newman, E Pachter, HL Gouge, TH Melis, M AF Glass, Nina E. Pinna, Antonio Masi, Antonio Rosman, Alan S. Neihaus, Dena Okochi, Shunpei Saunders, John K. Hatzaras, Ioannis Cohen, Steven Berman, Russell Newman, Elliot Pachter, H. Leon Gouge, Thomas H. Melis, Marcovalerio TI The Surgical Apgar Score Predicts Postoperative ICU Admission SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Risk assessment; Scoring systems; Surgery; Surgical Apgar score ID SURGERY; SYSTEMS; VETERAN; POSSUM C1 [Glass, Nina E.; Pinna, Antonio; Masi, Antonio; Neihaus, Dena; Okochi, Shunpei; Saunders, John K.; Hatzaras, Ioannis; Cohen, Steven; Berman, Russell; Newman, Elliot; Pachter, H. Leon; Gouge, Thomas H.; Melis, Marcovalerio] New York Harbor Healthcare Syst, Dept Surg, New York, NY 10044 USA. [Glass, Nina E.; Pinna, Antonio; Masi, Antonio; Saunders, John K.; Hatzaras, Ioannis; Cohen, Steven; Berman, Russell; Newman, Elliot; Pachter, H. Leon; Gouge, Thomas H.; Melis, Marcovalerio] NYU, Sch Med, Dept Surg, Brooklyn, NY USA. [Pinna, Antonio] Univ Sassari, I-07100 Sassari, Italy. [Rosman, Alan S.] Mt Sinai Sch Med, Gastroenterol Sect, New York, NY USA. [Rosman, Alan S.] Mt Sinai Sch Med, Program Med, New York, NY USA. [Rosman, Alan S.] James J Peters VAMC, New York, NY USA. RP Melis, M (reprint author), New York Harbor Healthcare Syst, Dept Surg, 423 E 23RD ST 4153 N, New York, NY 10044 USA. EM marcovalerio.melis@nyumc.org OI Gouge, Thomas/0000-0001-8381-4146; Pinna, Antonio/0000-0002-2187-6744; Berman, Russell/0000-0002-5026-5651 NR 14 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAR PY 2015 VL 19 IS 3 BP 445 EP 450 DI 10.1007/s11605-014-2733-8 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CB9PV UT WOS:000349965000008 PM 25572972 ER PT J AU Hill, AL Sumra, KK Russell, MM Yoo, J Ko, CY Hart, S Wainberg, Z Hecht, JR Lin, AY AF Hill, Amy L. Sumra, Kirandeep K. Russell, Marcia M. Yoo, James Ko, Clifford Y. Hart, Steven Wainberg, Zev Hecht, J. Randolph Lin, Anne Y. TI A Single Institution Experience in Compliance with Universal Screening for Lynch Syndrome in Colorectal Cancer SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Lynch syndrome; Universal screening; Microsatellite instability; Immunohistochemistry ID MICROSATELLITE INSTABILITY; IMMUNOHISTOCHEMISTRY; IMPLEMENTATION AB Detection of Lynch syndrome has the potential to reduce morbidity and mortality among patients and their family members due to beneficial screening and treatment options. Several institutions have begun to adopt universal rather than risk-stratified screening protocols, but the lack of 100 % compliance rates requires identification of system-level interventions to improve screening practices. We aimed to identify patient, tumor, and system factors associated with lack of screening and identify system-based interventions to improve Lynch syndrome screening. This study is a retrospective analysis of Lynch syndrome screening among colorectal cancer patients undergoing surgery in a single healthcare system. Two hundred and sixty-two patients who underwent surgery for colorectal cancer were studied. Rate of Lynch syndrome screening. We identified that 75 % of the total cohort was screened for Lynch syndrome. Of patients under the age of 50, 78 % percent were screened. Lower screening rates were found among patients with complete pathologic tumor response and lower pathologic stage of tumor. Higher screening rates were found at the academic hospital and with colorectal surgeons. In multivariable logistic regression analysis, lower screening rates were associated with community hospital location (OR, 0.22; 95 % CI, 0.08-0.56). Results may not be generalizable to different hospital settings. Several potential system-level interventions were identified to improve screening rates including an emphasis on improved provider communication. C1 [Hill, Amy L.; Lin, Anne Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Sumra, Kirandeep K.] Univ Arizona, Coll Med, Phoenix, AZ USA. [Russell, Marcia M.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Yoo, James] Tufts Med Ctr, Boston, MA 02111 USA. [Hart, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Wainberg, Zev; Hecht, J. Randolph] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Lin, AY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,72-247 CHS, Los Angeles, CA 90095 USA. EM aylin@mednet.ucla.edu NR 15 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAR PY 2015 VL 19 IS 3 BP 543 EP 550 DI 10.1007/s11605-014-2687-x PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CB9PV UT WOS:000349965000020 PM 25504462 ER PT J AU Moscovich, M Okun, MS Favilla, C Figueroa, KP Pulst, SM Perlman, S Wilmot, G Gomez, C Schmahmann, J Paulson, H Shakkottai, V Ying, S Zesiewicz, T Kuo, SH Mazzoni, P Bushara, K Xia, GB Ashizawa, T Subramony, SH AF Moscovich, M. Okun, Michael S. Favilla, Chris Figueroa, Karla P. Pulst, Stefan M. Perlman, Susan Wilmot, George Gomez, Christopher Schmahmann, Jeremy Paulson, Henry Shakkottai, Vikram Ying, Sarah Zesiewicz, Theresa Kuo, S. H. Mazzoni, P. Bushara, Khalaf Xia, Guangbin Ashizawa, Tetsuo Subramony, S. H. TI Clinical Evaluation of Eye Movements in Spinocerebellar Ataxias: A Prospective Multicenter Study SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID DOMINANT CEREBELLAR-ATAXIA; SLOW SACCADES; BRAIN-STEM; SCA2; ABNORMALITIES; POPULATION; NYSTAGMUS; FAMILIES; ATROPHY; TYPE-1 AB Background:Ocular motor abnormalities reflect the varied neuropathology of spinocerebellar ataxias (SCAs) and may serve to clinically distinguish the different SCAs. We analyzed the various eye movement abnormalities detected prospectively at the baseline visit during a large multicenter natural history study of SCAs 1, 2, 3, and 6.Methods:The data were prospectively collected from 12 centers in the United States in patients with SCAs 1, 2, 3, and 6, as part of the Clinical Research Consortium for Spinocerebellar Ataxias (NIH-CRC-SCA). Patient characteristics, ataxia rating scales, the Unified Huntington Disease Rating Scale functional examination, and clinical staging were used. Eye movement abnormalities including nystagmus, disorders of saccades and pursuit, and ophthalmoparesis were recorded, and factors influencing their occurrence were examined.Results:A total of 301 patients participated in this study, including 52 patients with SCA 1, 64 with SCA 2, 117 with SCA 3, and 68 with SCA 6. Although no specific ocular motor abnormality was pathognomonic to any SCA, significant differences were noted in their occurrence among different disorders. SCA 6 was characterized by frequent occurrence of nystagmus and abnormal pursuit and rarity of slow saccades and ophthalmoparesis and SCA 2 by the frequent occurrence of slow saccades and infrequent nystagmus and dysmetric saccades. SCA 1 and SCA 3 subjects had a more even distribution of eye movement abnormalities.Conclusions:Prospective data from a large cohort of patients with SCAs 1, 2, 3, and 6 provide statistical validation that the SCAs exhibit distinct eye movement abnormalities that are useful in identifying the genotypes. Many of the abnormalities correlate with greater disease severity measures. C1 [Moscovich, M.; Okun, Michael S.; Favilla, Chris; Xia, Guangbin; Ashizawa, Tetsuo; Subramony, S. H.] Univ Florida, McKnight Brain Inst, Dept Neurol, Gainesville, FL 32611 USA. [Figueroa, Karla P.; Pulst, Stefan M.] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Perlman, Susan] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Wilmot, George] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Gomez, Christopher] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Schmahmann, Jeremy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Paulson, Henry; Shakkottai, Vikram] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Ying, Sarah] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Zesiewicz, Theresa] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA. [Kuo, S. H.; Mazzoni, P.] Columbia Univ, Dept Neurol, New York, NY USA. [Bushara, Khalaf] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. RP Subramony, SH (reprint author), Univ Florida, Coll Med, Dept Neurol, 1149 Newell Dr,L3-100, Gainesville, FL 32611 USA. EM s.subramony@neurology.ufl.edu OI Okun, Michael/0000-0002-6247-9358; Favilla, Christopher/0000-0003-0871-9549 FU NIH [NS068897] FX Supported by NIH Grant NS068897 to T. Ashizawa. The remaining authors report no conflicts of interest. NR 26 TC 4 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD MAR PY 2015 VL 35 IS 1 BP 16 EP 21 DI 10.1097/WNO.0000000000000167 PG 6 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA CC6GD UT WOS:000350462300008 PM 25259863 ER PT J AU Hirsch, JA Turk, AS Mocco, J Fiorella, DJ Jayaraman, MV Meyers, PM Yoo, AJ Manchikanti, L AF Hirsch, Joshua A. Turk, Aquilla S. Mocco, J. Fiorella, David J. Jayaraman, Mahesh V. Meyers, Phillip M. Yoo, Albert J. Manchikanti, Laxmaiah TI Evidence-based clinical practice for the neurointerventionalist SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID RANDOMIZED-TRIAL; MANAGEMENT; STANDARDS; MEDICINE; GUIDELINES; THERAPY; STROKE; CARE AB The field of neurointerventional (NI) surgery has developed in the context of technologic innovation. Many treatments readily provided in 2014 would have been hard to imagine as recently as 10 years ago. The reality of present day NI care is that, while providers, payors, policy makers and patients rely on evidence to guide NI decision-making, the available data are often less robust than participants might desire. In this paper we will explore the fundamentals of evidence-based clinical practice. C1 [Hirsch, Joshua A.; Yoo, Albert J.] Harvard Univ, Sch Med, Neuroendovasc Program, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Turk, Aquilla S.] Med Univ S Carolina, Dept Neurosurg, Charleston, SC 29425 USA. [Turk, Aquilla S.] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. [Mocco, J.] Vanderbilt Univ, Med Ctr, Dept Neurosurg, Nashville, TN USA. [Fiorella, David J.] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY 11794 USA. [Jayaraman, Mahesh V.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. [Meyers, Phillip M.] Columbia Univ, Dept Radiol, New York, NY USA. [Meyers, Phillip M.] Columbia Univ, Dept Neurol Surg, New York, NY USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. RP Hirsch, JA (reprint author), Harvard Univ, Sch Med, Neuroendovasc Program, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Hirsch@snisonline.org NR 30 TC 2 Z9 2 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAR PY 2015 VL 7 IS 3 BP 225 EP 228 DI 10.1136/neurintsurg-2014-011155 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA CC6RB UT WOS:000350493600017 PM 24578482 ER PT J AU Manchikanti, L Candido, KD Benyamin, RM Hirsch, JA AF Manchikanti, Laxmaiah Candido, Kenneth D. Benyamin, Ramsin M. Hirsch, Joshua A. TI Results of comprehensive medical management of lumbar disorders questioned SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Letter ID CAUDAL EPIDURAL INJECTIONS; CENTRAL SPINAL STENOSIS; 2-YEAR FOLLOW-UP; LOW-BACK-PAIN; DISC HERNIATION; COST-EFFECTIVENESS; DOUBLE-BLIND; SURGERY SYNDROME; CONTROLLED-TRIAL; SPONDYLOLISTHESIS C1 [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Candido, Kenneth D.] Advocate Illinois Mason Med Ctr, Chicago, IL USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Urbana, IL 61801 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), Univ Louisville, Louisville, KY 40292 USA. NR 15 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 EI 1547-5646 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD MAR PY 2015 VL 22 IS 3 BP 332 EP 333 DI 10.3171/2014.6.SPINE14605 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CC3RG UT WOS:000350266300017 PM 25525961 ER PT J AU Li, CB Hosseini, A Tsai, TY Kwon, YM Li, GA AF Li, Chunbao Hosseini, Ali Tsai, Tsung-Yuan Kwon, Young-Min Li, Guoan TI Articular Contact Kinematics of the Knee Before and After a Cruciate Retaining Total Knee Arthroplasty SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE TKA; knee osteoarthritis; fluoroscopy; in vivo kinematics; contact kinematics ID TIBIAL POLYETHYLENE INSERT; IN-VIVO KINEMATICS; OSTEOARTHRITIC KNEES; JOINT KINEMATICS; BEARING; FLEXION; LIGAMENT; VITRO; TKA; DESIGN AB Accurate knowledge of tibiofemoral articular contact kinematics of the knee after total knee arthroplasty (TKA) is important for understanding the intrinsic knee biomechanics and improving the longevity of the components. The objective of this study was to compare the in vivo articular contact kinematics of the knees with end-stage medial osteoarthritis (OA) during a weight-bearing, single leg lunge activity before and after a posterior cruciate retaining TKA (CR-TKA) using a dual fluoroscopic imaging technique. We found that the CR-TKA resulted in more posterior contact positions on the tibial surface and a reduced range of motion in the medial and lateral compartments. The distances between medial and lateral contact locations in the CR-TKA knees were statistically larger than the OA knees. The articular contact centers have shifted from medial side of the tibial plateau pre-operatively to the lateral side after operation. This study indicated that the CR-TKA resulted in significant changes in contact kinematics of the knees in both anteroposterior and mediolateral directions. Further studies are needed to determine the influence of the altered in vivo contact kinematics on the longevity of polyethylene liner and long term clinical outcomes of the TKA. (c) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???-???, 2015. C1 [Li, Chunbao; Hosseini, Ali; Tsai, Tsung-Yuan; Kwon, Young-Min; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Li, Chunbao; Hosseini, Ali; Tsai, Tsung-Yuan; Kwon, Young-Min; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Li, Chunbao] Chinese Peoples Liberat Army Gen Hosp, Dept Orthopaed Surg, Beijing 1000853, Peoples R China. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@mgh.harvard.edu OI Tsai, Tsung-Yuan/0000-0003-1522-2987 FU Department of Orthopaedic Surgery at Massachusetts General Hospital; Chinese PLA General Hospital, Beijing FX The authors thank the support of the Department of Orthopaedic Surgery at Massachusetts General Hospital, and the scholarship provided by the Chinese PLA General Hospital, Beijing. The technical assistance of Drs. Harry Rubash, Andrew Freiberg, and Yujie Liu is greatly appreciated. NR 48 TC 4 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD MAR PY 2015 VL 33 IS 3 BP 349 EP 358 DI 10.1002/jor.22764 PG 10 WC Orthopedics SC Orthopedics GA CC6JZ UT WOS:000350472500010 PM 25469483 ER PT J AU Langlois, J Zaoui, A Scemama, C Martell, J Bragdon, C Hamadouche, M AF Langlois, Jean Zaoui, Amine Scemama, Caroline Martell, John Bragdon, Charles Hamadouche, Moussa TI Validation of a Computer-Assisted Method for Measurement of Radiographic Wear in Total Hip Arthroplasty Using All Polyethylene Cemented Acetabular Components SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE total hip replacement; polyethylene wear; error measurement; precision measurement; accuracy measurement ID RADIO STEREOMETRIC ANALYSIS; ACCURACY; PRECISION; SOCKET; MODEL AB Although cemented all polyethylene (PE) cups have been routinely used in total hip arthroplasty for decades, no computer-assisted method for measurement of radiographic wear has ever been specifically validated for these implants. Using a validated hip phantom model, AP plain hip radiographs were obtained consecutively for eight simulated wear positions. A version of Martell's Hip Analysis Suite software dedicated to all polyethylene sockets was used by three different examiners of varied experience. Bias (mean, standard deviation and 95% confidence interval limit), repeatability (standard deviation and 95% limit) and reproducibility (standard deviation and 95% limit) for two-dimensional wear measurements were assessed, as recommended by the current ASTM guidelines. Using this protocol, the dedicated software showed an overall mean bias of 0.089 +/- 0.060mm (mean +/- SD), and 0.118mm for 95% CI limit. Repeatability (intra examiner) standard deviation and 95% limit were respectively 0.106mm and 0.292mm. Reproducibility (inter examiner) standard deviation and 95% limit were respectively 0.112mm and 0.308mm. Martell Hip Analysis for all PE cemented cups is a reliable and low-cost instrument in the assessment of wear, despite being less precise than its original version dedicated to cementless components. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???-???, 2015. C1 [Langlois, Jean; Zaoui, Amine; Scemama, Caroline; Hamadouche, Moussa] Univ Paris 05, Hop Cochin, APHP, Serv Chirurg Orthoped & Traumatol, F-75679 Paris 14, France. [Martell, John] Univ Chicago, Dept Orthopaed, Chicago, IL 60637 USA. [Bragdon, Charles] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Lab, Boston, MA 02114 USA. [Bragdon, Charles] Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. [Bragdon, Charles] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Langlois, J (reprint author), Univ Paris 05, Hop Cochin, APHP, Serv Chirurg Orthoped & Traumatol, 27 Rue Faubourg St Jacques, F-75679 Paris 14, France. EM jeangast@gmail.com FU Fulbright Foundation; Arthur Sachs Foundation FX Grant sponsor: Fulbright and the Arthur Sachs Foundations. NR 19 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD MAR PY 2015 VL 33 IS 3 BP 417 EP 420 DI 10.1002/jor.22777 PG 4 WC Orthopedics SC Orthopedics GA CC6JZ UT WOS:000350472500019 PM 25564735 ER PT J AU Houghteling, PD Walker, WA AF Houghteling, Pearl D. Walker, W. Allan TI Why Is Initial Bacterial Colonization of the Intestine Important to Infants' and Children's Health? SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review DE breast-feeding; cesarean section; immune programming; infant colonization; microbiome ID INFLAMMATORY-BOWEL-DISEASE; RECURRENT CLOSTRIDIUM-DIFFICILE; IMMUNE-MEDIATED INFLAMMATION; HUMAN-MILK OLIGOSACCHARIDES; ACTIVE ULCERATIVE-COLITIS; TRICHURIS-SUIS THERAPY; DIET-INDUCED OBESITY; GUT MICROBIOTA; BREAST-MILK; NECROTIZING ENTEROCOLITIS AB Microbial colonization of the infant occurs during a critical time window for immune and gastrointestinal development. Infant colonization sets the stage for the adult microbiome. This review is a broad survey of the factors affecting infant colonization and the downstream effects on gastrointestinal health and disease. Major topics affecting colonization include initial inoculation dependent on birth mode, the impact of breast-feeding, and inside-out modulation of the developing microbiome by the immune system. Major outcomes of colonization include the timing-dependent education of the neonatal immune system, which is interconnected with barrier function and metabolism. These all engage in further continuing cross-talk with the microbiome, genetics, and nutrition. This review also briefly examines mechanisms of disease resulting from disrupted colonization as well as nutritional and microbial therapies. C1 [Houghteling, Pearl D.; Walker, W. Allan] Massachusetts Gen Hosp Children, Mucosal Immunol & Biol Res Ctr, Charlestown, MA USA. RP Walker, WA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM wwalker@partners.org FU NIH [P30 DK040561, P01 DK033506, R01 HD012437, R01 HD059126, 3T32DK007191-39S1] FX This study was supported by NIH grants (P30 DK040561, P01 DK033506, R01 HD012437, R01 HD059126, and 3T32DK007191-39S1). NR 136 TC 18 Z9 23 U1 9 U2 73 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 MAR PY 2015 VL 60 IS 3 BP 294 EP 307 DI 10.1097/MPG.0000000000000597 PG 14 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA CC7DE UT WOS:000350527100008 PM 25313849 ER PT J AU Corey, KE Vuppalanchi, R Vos, M Kohli, R Molleston, JP Wilson, L Unalp-Arida, A Cummings, OW Lavine, JE Chalasani, N AF Corey, Kathleen E. Vuppalanchi, Raj Vos, Miriam Kohli, Rohit Molleston, Jean P. Wilson, Laura Unalp-Arida, Aynur Cummings, Oscar W. Lavine, Joel E. Chalasani, Naga CA Nonalcoholic Steatohepatitis TI Improvement in Liver Histology Is Associated With Reduction in Dyslipidemia in Children With Nonalcoholic Fatty Liver Disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE cardiovascular disease risk; lipids; metformin; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; non-high-density lipoprotein cholesterol ID DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR RISK-FACTORS; INTIMA-MEDIA THICKNESS; OBESE ADOLESCENTS; INSULIN-RESISTANCE; METABOLIC SYNDROME; CONTROLLED-TRIAL; YOUNG-ADULTS; FOLLOW-UP; ATHEROSCLEROSIS AB Objectives: Nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease among US children, may be associated with cardiovascular disease (CVD) risk. The present study sought to determine the prevalence of dyslipidemia in children with NAFLD and assess dyslipidemia by liver histology and histologic changes. Methods: Individuals in the Treatment of NAFLD in Children (TONIC) trial were included (N=173). In the TONIC trial, children with NAFLD were randomized to vitamin E, metformin, or placebo for 96 weeks. Nonalcoholic steatohepatitis (NASH) improved in 56 children. Change in lipid levels from baseline and 96 weeks was compared between patients with and without histologic improvement and with and without NASH. Results: Dyslipidemia was frequent, with low high-density lipoprotein (HDL) (<40 mg/dL) in 61.8%, hypertriglyceridemia (>130 mg/dL) in 50.3%, hypercholesterolemia (>200 mg/dL) in 23.7%, elevated low-density lipoprotein (LDL) (>130 mg/dL) in 21.5%, elevated non-HDL cholesterol (non-HDL-C) (>145 mg/dL) in 35.2%, and triglycerides/HDL >3.0 in 57.2% of patients. Histologic improvement was associated with significant decreases in cholesterol (-11.4 mg/dL vs 1.9 mg/dL, P = 0.04), LDL (-11.2 mg/dL vs -2.1 mg/dL, P = 0.04), and non-HDL-C (-8.8 mg/dL vs 0.5 mg/dL. P =0.03) compared with those without improvement. Children with NASH resolution had significant decreases in cholesterol (-10.0 mg/dL vs -0.9 mg/dL, P = 0.02) and non-HDL-C (-7.3 mg/dL vs 1.1 mg/dL, P = 0.01) compared with those without NASH resolution. There was no improvement in triglycerides, HDL level, or triglycerides/HDL ratio in either group. Conclusions: Dyslipidemia is frequent in children with NAFLD. NASH resolution and histologic improvement are associated with improvements in some forms of dyslipidemia. C1 [Corey, Kathleen E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vuppalanchi, Raj; Molleston, Jean P.; Cummings, Oscar W.; Chalasani, Naga] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Vos, Miriam] Emory Univ, Sch Med, Atlanta, GA USA. [Kohli, Rohit] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Wilson, Laura; Unalp-Arida, Aynur] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Lavine, Joel E.] Columbia Univ, New York, NY USA. RP Corey, KE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM kcorey@partners.org OI Vuppalanchi, Raj/0000-0003-0637-1577; kohli, Rohit/0000-0002-0198-7703 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health General Clinical Research Centers [UL1RR024989, UL1RR024128, M01RR000750, UL1RR024131, M01RR000827, UL1RR02501401, M01RR000065, M01RR00188, M01RR020359]; NIH [K23DK099422-0]; National Institute of Diabetes and Digestive and Kidney Disease; Clinical and Translational Science FX The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, and U01DK061713. The present study is supported in part by the Intramural Research Program of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Other grant support includes the following National Institutes of Health General Clinical Research Centers or Clinical and Translational Science Awards: UL1RR024989, UL1RR024128, M01RR000750, UL1RR024131, M01RR000827, UL1RR02501401, M01RR000065, M01RR00188, and M01RR020359.; K.E.C. receives support from the NIH K23DK099422-0. TONIC trial is supported by the National Institute of Diabetes and Digestive and Kidney Disease and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The other authors report no conflicts of interest. NR 40 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAR PY 2015 VL 60 IS 3 BP 360 EP 367 DI 10.1097/MPG.0000000000000584 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA CC7DE UT WOS:000350527100019 PM 25714579 ER PT J AU Escobar, DA Botero-Quintero, AM Kautza, BC Luciano, J Loughran, P Darwiche, S Rosengart, MR Zuckerbraun, BS Gomez, H AF Escobar, Daniel A. Botero-Quintero, Ana M. Kautza, Benjamin C. Luciano, Jason Loughran, Patricia Darwiche, Sophie Rosengart, Matthew R. Zuckerbraun, Brian S. Gomez, Hernando TI Adenosine monophosphate-activated protein kinase activation protects against sepsis-induced organ injury and inflammation SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Sepsis; AMPK; Energy; Inflammation; Endothelium; Organ injury ID NF-KAPPA-B; VEIN ENDOTHELIAL-CELLS; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBONUCLEOSIDE; MITOCHONDRIAL BIOGENESIS; ENERGY SENSOR; IN-VITRO; ACADESINE; AUTOPHAGY; AMPK; REPERFUSION AB Background: Mortality in sepsis is most often attributed to the development of multiple organ failure. In sepsis, inflammation-mediated endothelial activation, defined as a proinflammatory and procoagulant state of the endothelial cells, has been associated with severity of disease. Thus, the objective of this study was to test the hypothesis that adenosine monophosphate-activated protein kinase (AMPK) activation limits inflammation and endothelium activation to protect against organ injury in sepsis. 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), which is an adenosine monophosphate analog, has been used to upregulate activity of AMPK. Compound C is a cell-permeable pyrrazolopyrimidine compound that inhibits AMPK activity. Methods: Wild-type mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice were randomized to vehicle, AICAR, or compound C. Mouse kidney endothelial cells were used for in vitro experiments. Renal and liver function were determined by serum cystatin C, blood urea nitrogen (BUN), creatinine, and alanine aminotransferase. Serum cytokines were measured by enzyme-linked immunosorbent assay. Microvascular injury was determined using Evans blue dye and electron microscopy. Immunohistochemistry was used to measure protein levels of phospho-AMPK (p-AMPK), microtubule-associated protein 1A/1B-light chain 3 (LC3), and intracellular adhesion molecule. LC3 levels were used as a measure of autophagosome formation. Results: AICAR decreased liver and kidney injury induced by CLP and minimized cytokine elevation in vivo and in vitro. CLP increased renal and hepatic phosphorylation of AMPK and autophagic signaling as determined by LC3. Inhibition of AMPK with compound C prevented CLP-induced autophagy and exacerbated tissue injury. Additionally, CLP led to endothelial injury as determined by electron microscopy and Evans blue dye extravasation, and AICAR limited this injury. Furthermore, AICAR limited CLP and lipopolysaccharide (LPS)-induced upregulation of intracellular adhesion molecule in vivo and in vitro and decreased LPS-induced neutrophil adhesion in vitro. Conclusions: In this model, activation of AMPK was protective, and AICAR minimized organ injury by decreasing inflammatory cytokines and endothelial activation. These data suggest that AMPK signaling influences sepsis or LPS-induced endothelial activation and organ injury. (C) 2015 Elsevier Inc. All rights reserved. C1 [Escobar, Daniel A.; Botero-Quintero, Ana M.; Kautza, Benjamin C.; Luciano, Jason; Loughran, Patricia; Darwiche, Sophie; Rosengart, Matthew R.; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Rosengart, Matthew R.; Gomez, Hernando] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15261 USA. [Zuckerbraun, Brian S.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Dept Surg, Pittsburgh, PA USA. [Zuckerbraun, Brian S.; Gomez, Hernando] Univ Pittsburgh, Dept Crit Care Med, Ctr Crit Care Nephrol, Pittsburgh, PA USA. RP Gomez, H (reprint author), Univ Pittsburgh, Dept Crit Care Med, 640A Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM gomezh@upmc.edu FU National Institutes of Health [R01 GM082830, 1K12HL109068-02]; Veterans Affairs Merit Award [1I01BX000566]; Department of Defense [DM102439] FX No conflict of interest is declared. This work is supported by National Institutes of Health grants R01 GM082830 (B.S.Z.), 1K12HL109068-02 (H.G.), Veterans Affairs Merit Award 1I01BX000566 (B.S.Z.), and Department of Defense DM102439 (B.S.Z.). NR 43 TC 13 Z9 15 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD MAR PY 2015 VL 194 IS 1 BP 262 EP 272 DI 10.1016/j.jss.2014.10.009 PG 11 WC Surgery SC Surgery GA CC5FH UT WOS:000350384000034 PM 25456115 ER PT J AU Nansel, T Haynie, D Lipsky, L Mehta, S Laffel, L AF Nansel, Tonja Haynie, Denise Lipsky, Leah Mehta, Sanjeev Laffel, Lori TI Little Variation in Diet Cost Across Wide Ranges of Overall Dietary Quality among Youth with Type 1 Diabetes SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Type 1 diabetes; Cost; Spending; Adolescents; Children ID LOW-INCOME WOMEN; ENERGY-DENSE DIETS; SOCIOECONOMIC-STATUS; NUTRITIONAL QUALITY; NUTRIENT DATABASE; FOOD-CONSUMPTION; AMERICAN WOMEN; HEALTHFUL DIET; CHILDREN; ADOLESCENTS AB We examined the association of diet quality with diet cost in a sample of youth with type 1 diabetes, for whom diet is an important component of medical management. Differences in food group spending by diet quality were also examined to identify potential budgetary reallocation to improve overall diet quality. Families of 252 youth with type 1 diabetes aged 8 to 18 years completed 3-day youth diet records. Cost of each food reported was calculated based on the average price obtained from two online grocery stores. Diet cost was estimated as average daily cost of foods consumed. The Healthy Eating Index 2005 (HEI2005), Nutrient Rich Foods Index version 9.3, and Whole Plant Food Density scores were evaluated. Differences in mean daily diet cost across tertiles of HEI2005, Nutrient Rich Foods Index version 9.3, and Whole Plant Food Density were modest, with none reaching statistical significance. Those in the upper tertile of HEI2005 spent more on whole fruit, whole grains, lean meat, and low-fat dairy, and less on high-fat meat and high-fat dairy compared with those in the lower tertiles. Higher-quality diets can be obtained at comparable costs to lesser-quality diets, suggesting that cost need not be an insurmountable barrier to more healthful eating. Reallocation of spending may increase overall quality without substantially increasing overall spending. Findings suggest potential strategies for assisting families of youth with type 1 diabetes in identifying cost-effective ways to achieve a more healthful diet. C1 [Nansel, Tonja; Haynie, Denise; Lipsky, Leah] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. [Mehta, Sanjeev; Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02115 USA. RP Nansel, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B13, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program [HHSN267200703434C] FX This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program (contract no. HHSN267200703434C). NR 55 TC 4 Z9 4 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 EI 2212-2680 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD MAR PY 2015 VL 115 IS 3 BP 433 EP U115 DI 10.1016/j.jand.2014.07.035 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CC3FM UT WOS:000350231700014 PM 25266245 ER PT J AU Yu, HA Sima, CS Shen, RL Kass, S Gainor, J Shaw, A Hames, M Iams, W Aston, J Lovly, CM Horn, L Lydon, C Oxnard, GR Kris, MG Ladanyi, M Riely, GJ AF Yu, Helena A. Sima, Camelia S. Shen, Ronglai Kass, Samantha Gainor, Justin Shaw, Alice Hames, Megan Iams, Wade Aston, Jonathan Lovly, Christine M. Horn, Leora Lydon, Christine Oxnard, Geoffrey R. Kris, Mark G. Ladanyi, Marc Riely, Gregory J. TI Prognostic Impact of KRAS Mutation Subtypes in 677 Patients with Metastatic Lung Adenocarcinomas SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; KRAS; Prognostic markers; Adenocarcinoma; Metastatic ID K-RAS MUTATIONS; GROWTH-FACTOR RECEPTOR; COLORECTAL-CANCER; PHASE-III; ONCOGENE SUBSTITUTIONS; ADJUVANT CHEMOTHERAPY; CLINICAL-TRIALS; EGFR MUTATIONS; NEVER-SMOKERS; CELL AB Background: We previously demonstrated that patients with metastatic KRAS mutant lung cancers have a shorter survival compared with patients with KRAS wild-type cancers. Recent reports have suggested different clinical outcomes and distinct activated signaling pathways depending on KRAS mutation subtype. To better understand the impact of KRAS mutation subtype, we analyzed data from 677 patients with KRAS mutant metastatic lung cancer. Methods: We reviewed all patients with metastatic or recurrent lung cancers found to have KRAS mutations over a 6-year time period. We evaluated the associations among KRAS mutation type, clinical factors, and overall survival in univariate and multivariate analyses. Any significant findings were validated in an external multi-institution patient dataset. Results: Among 677 patients with KRAS mutant lung cancers (53 at codon 13, 624 at codon 12), there was no difference in overall survival for patients when comparing KRAS transition versus transversion mutations (p = 0.99), smoking status (p = 0.33), or when comparing specific amino acid substitutions (p = 0.20). In our dataset, patients with KRAS codon 13 mutant tumors (n = 53) had shorter overall survival compared with patients with codon 12 mutant tumors (n = 624) (1.1 versus 1.3 years, respectively; p = 0.009), and the findings were confirmed in a multivariate Cox model controlling for age, sex, and smoking status (hazard ratio: 1.52, 95% confidence interval: 1.11-2.08; p = 0.008). In an independent validation set of tumors from 682 patients with stage IV KRAS mutant lung cancers, there was no difference in survival between patients with KRAS codon 13 versus codon 12 mutations (1.0 versus 1.1 years, respectively; p = 0.41). Conclusions: Among individuals with KRAS mutant metastatic lung cancers treated with conventional therapy, there are no apparent differences in outcome based on KRAS mutation subtype. C1 [Yu, Helena A.; Kass, Samantha; Kris, Mark G.; Riely, Gregory J.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv,Div Solid Tumor Oncol, New York, NY USA. [Sima, Camelia S.; Shen, Ronglai] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA. [Ladanyi, Marc] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA. [Gainor, Justin; Shaw, Alice] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. [Hames, Megan; Iams, Wade; Aston, Jonathan; Lovly, Christine M.; Horn, Leora] Vanderbilt Ingram Canc Ctr, Dept Med, Franklin, TN USA. [Lydon, Christine; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Riely, GJ (reprint author), Mem Sloan Kettering Canc Ctr, 300 East 66th St, New York, NY 10065 USA. EM rielyg@mskcc.org OI Kris, Mark/0000-0002-7317-5341 FU NIH [P01CA129243] FX This study was supported by NIH funding, P01CA129243 (Mark G. Kris). The sponsor played no role in data collection, analysis or interpretation. NR 47 TC 9 Z9 9 U1 1 U2 3 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 MAR PY 2015 VL 10 IS 3 BP 431 EP 437 DI 10.1097/JTO.0000000000000432 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CC1QX UT WOS:000350118000010 PM 25415430 ER PT J AU Shuster, M Morley, K Logan, J Sequist, LV Shaw, A Fidias, P Kroshinsky, D AF Shuster, Marina Morley, Keith Logan, Jennifer Sequist, Lecia V. Shaw, Alice Fidias, Panos Kroshinsky, Daniela TI Lipodermatosclerosis Secondary to Pemetrexed Use SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article ID CELL LUNG-CANCER C1 [Shuster, Marina] Harvard Univ, Sch Med, Boston, MA USA. [Morley, Keith] Harvard Combined Dermatol Residency Program, Boston, MA USA. [Logan, Jennifer; Sequist, Lecia V.; Shaw, Alice; Fidias, Panos] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kroshinsky, D (reprint author), 50 Staniford St,Suite 200, Boston, MA 02114 USA. EM dkroshinsky@mgh.harvard.edu FU Pfizer; Novartis; Genentech; Roche; Ignyta; Ariad; Chugai; Daiichi-sankyo FX Panos Fidias was previously a paid board member of Genentech. Alice Shaw is currently a paid consultant for Pfizer, Novartis, Genentech, Roche, and Ignyta and was previously a paid consultant for Ariad, Chugai, and Daiichi-sankyo. Jennifer Logan was previously a paid consultant for Novartis. For the remaining authors none were declared. NR 7 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAR PY 2015 VL 10 IS 3 BP E11 EP E12 DI 10.1097/JTO.0000000000000426 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CC1QX UT WOS:000350118000001 PM 25695225 ER PT J AU White, EA Kramer, RE Hwang, JH Fernando, ATP Naetar, N Hahn, WC Roberts, TM Schaffhausen, BS Livingston, DM Howley, PM AF White, Elizabeth A. Kramer, Rebecca E. Hwang, Justin H. Fernando, Arun T. Pores Naetar, Nana Hahn, William C. Roberts, Thomas M. Schaffhausen, Brian S. Livingston, David M. Howley, Peter M. TI Papillomavirus E7 Oncoproteins Share Functions with Polyomavirus Small T Antigens SO JOURNAL OF VIROLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; HUMAN CELL-TRANSFORMATION; PROTEIN PHOSPHATASE 2A; LARGE TUMOR-ANTIGEN; MIDDLE T; SV40; TYPE-16; ASSOCIATION; PP2A; IDENTIFICATION AB Many of the small DNA tumor viruses encode transforming proteins that function by targeting critical cellular pathways involved in cell proliferation and survival. In this study, we have examined whether some of the functions of the polyomavirus small T antigens (ST) are shared by the E6 and E7 oncoproteins of two oncogenic papillomaviruses. Using three different assays, we have found that E7 can provide some simian virus 40 (SV40) or murine polyomavirus (PyV) ST functions. Both human papillomavirus 16 (HPV16) and bovine papillomavirus (BPV1) E7 proteins are capable of partially substituting for SV40 ST in a transformation assay that also includes SV40 large T antigen, the catalytic subunit of cellular telomerase, and oncogenic Ras. Like SV40 ST, HPV16 E7 has the ability to override a quiescence block induced by mitogen deprivation. Like PyV ST, it also has the ability to inhibit myoblast differentiation. At least two of these activities are dependent upon the interaction of HPV16 E7 with retinoblastoma protein family members. For small T antigens, interaction with PP2A is needed for each of these functions. Even though there is no strong evidence that E6 or E7 share the ability of small T to interact with PP2A, E7 provides these functions related to cellular transformation. IMPORTANCE DNA tumor viruses have provided major insights into how cancers develop. Some viruses, like the human papillomaviruses, can cause cancer directly. Both the papillomaviruses and the polyomaviruses have served as tools for understanding pathways that are often perturbed in cancer. Here, we have compared the functions of transforming proteins from several DNA tumor viruses, including two papillomaviruses and two polyomaviruses. We tested the papillomavirus E6 and E7 oncoproteins in three functional assays and found that E7 can provide some or all of the functions of the SV40 small T antigen, another well-characterized oncoprotein, in two of these assays. In a third assay, papillomavirus E7 has the same effect as the murine polyomavirus small T protein. In summary, we report several new functions for the papillomavirus E7 proteins, which will contribute new insights into the roles of viruses in cancer and the cellular pathways they perturb in carcinogenesis. C1 [White, Elizabeth A.; Kramer, Rebecca E.; Howley, Peter M.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02138 USA. [Hwang, Justin H.; Schaffhausen, Brian S.] Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. [Fernando, Arun T. Pores; Naetar, Nana; Hahn, William C.; Roberts, Thomas M.; Livingston, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Fernando, Arun T. Pores; Naetar, Nana; Hahn, William C.; Roberts, Thomas M.; Livingston, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Howley, PM (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02138 USA. EM peter_howley@hms.harvard.edu FU NIH [P01CA050661]; NRSA grant [F32AI080075] FX This work was supported by NIH grant P01CA050661 (P.M.H., T.M.R., B.S.S., D.M.L., and W.C.H.) and individual NRSA grant F32AI080075 to E.A.W. NR 38 TC 3 Z9 3 U1 0 U2 2 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 MAR PY 2015 VL 89 IS 5 BP 2857 EP 2865 DI 10.1128/JVI.03282-14 PG 9 WC Virology SC Virology GA CC2XD UT WOS:000350207400037 PM 25540383 ER PT J AU Ketteler, M Elder, GJ Evenepoel, P Ix, JH Jamal, SA Lafage-Proust, MH Shroff, R Thadhani, RI Tonelli, MA Kasiske, BL Wheeler, DC Leonard, MB AF Ketteler, Markus Elder, Grahame J. Evenepoel, Pieter Ix, Joachim H. Jamal, Sophie A. Lafage-Proust, Marie-Helene Shroff, Rukshana Thadhani, Ravi I. Tonelli, Marcello A. Kasiske, Bertram L. Wheeler, David C. Leonard, Mary B. TI Revisiting KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder: a commentary from a Kidney Disease: Improving Global Outcomes controversies conference SO KIDNEY INTERNATIONAL LA English DT Review DE calcium; CKD-MBD; clinical practice guideline; phosphate; PTH; renal osteodystrophy ID RANDOMIZED CONTROLLED-TRIAL; PHOSPHATE BINDERS; RENAL-DISEASE; VITAMIN-D; CKD-MBD; CALCIUM; MORTALITY; FRACTURE; DENSITY; CALCIFICATION AB A new definition and classification of chronic kidney disease-mineral and bone disorder (CKD-MBD) was proposed in 2005 and it was later followed by a guideline publication on this topic from Kidney Disease: Improving Global Outcomes (KDIGO) in 2009. This work recognized that CKD-MBD is a syndrome of bone abnormalities, laboratory abnormalities, and vascular calcification linked to fractures, cardiovascular disease, and mortality. Because of limited data at the time of the original guideline systematic review, many of the recommendations were cautiously vague. KDIGO convened a Controversies Conference in October 2013 to review the CKD-MBD literature published since the 2009 guideline. Specifically, the objective of this conference was to determine whether sufficient new data had emerged to support a reassessment of the CKD-MBD guideline and if so to determine the scope of these potential revisions. This report summarizes the results of these proceedings, highlighting important new studies conducted in the interval since the original KDIGO CKD-MBD guideline. C1 [Ketteler, Markus] Klinikum Coburg GmbH, Div Nephrol, D-96450 Coburg, Germany. [Elder, Grahame J.] Westmead Hosp, Dept Renal Med, Sydney, NSW, Australia. [Elder, Grahame J.] Garvan Inst Med Res, Osteoporosis & Bone Biol Div, Sydney, NSW, Australia. [Evenepoel, Pieter] Univ Hosp Leuven, Dept Nephrol, Leuven, Belgium. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. [Jamal, Sophie A.] Womens Coll Res Inst, Toronto, ON, Canada. [Lafage-Proust, Marie-Helene] Fac Med, INSERM, U1059, St Etienne, France. [Shroff, Rukshana] Great Ormond St Hosp Sick Children, Nephrol Unit, London WC1N 3JH, England. [Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Tonelli, Marcello A.] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Tonelli, Marcello A.] Univ Alberta, Dept Publ Hlth Sci, Edmonton, AB, Canada. [Kasiske, Bertram L.] Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA. [Wheeler, David C.] UCL, London, England. [Leonard, Mary B.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Ketteler, M (reprint author), Klinikum Coburg GmbH, Div Nephrol, Ketschendorfer St 33, D-96450 Coburg, Germany. EM markus.ketteler@klinikum-coburg.de RI Shroff, Rukshana/C-7347-2008; Tonelli, Marcello/B-3028-2009 OI Shroff, Rukshana/0000-0001-8501-1072; FU Abbvie; Amgen; Fresenius; Medice; Mitsubishi; Sanofi; Shire; Vifor; Vifor Australia; AstraZeneca; Keryx; Servier; Kaneka; Abbott Laboratories; Astellas; Baxter; F Hoffmann-La Roche; Janssen; Merck Sharp Dohme; Otsuka; AstraZeneca/British Heart Foundation; Kidney Research UK; Medical Research Council; Healthcare Quality Improvement Partnership FX MK declared having received consultancy fees and speaker honoraria from Abbvie, Amgen, Fresenius, Medice, Mitsubishi, Sanofi, Shire, and Vifor. GJE declared having received consultancy fees from Amgen, Shire, and Vifor Australia; speaker honoraria from Amgen, Sanofi and Shire. PE declared having received consultancy fees from Amgen; speaker honoraria from Amgen, Astellas, Fresenius, and Shire; research support from Amgen. JHI declared having received consultancy fees from AstraZeneca and Keryx; speaker honoraria from Shire. SAJ declared having received consultancy fees from Amgen and Sanofi; speaker honoraria from Amgen, Bayer, Sanofi/Genzyme, and Warner Chilcott/Actavis. MHLP declared having received research support from Servier. RIT declared having received consultancy fees from Fresenius and research support from Kaneka. MAT declared having received research support from Abbott Laboratories through a peer reviewed grant to the Canadian Institutes of Health Research. DCW declared having received consultancy fees from Abbvie, Amgen, Astellas, Baxter, F Hoffmann-La Roche, Janssen, Merck Sharp & Dohme, Otsuka, and Vifor; research funding from AstraZeneca/British Heart Foundation, Kidney Research UK, Medical Research Council, Healthcare Quality Improvement Partnership; speaker honoraria from Amgen and Otsuka. BLK, MBL and RS reported no relevant disclosures. NR 23 TC 30 Z9 33 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2015 VL 87 IS 3 BP 502 EP 508 DI 10.1038/ki.2014.425 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CC7FO UT WOS:000350533300006 PM 25651364 ER PT J AU Ivers, LC Hilaire, IJ Teng, JE Almazor, CP Jerome, JG Ternier, R Boncy, J Buteau, J Murray, MB Harris, JB Franke, MF AF Ivers, Louise C. Hilaire, Isabelle J. Teng, Jessica E. Almazor, Charles P. Jerome, J. Gregory Ternier, Ralph Boncy, Jacques Buteau, Josiane Murray, Megan B. Harris, Jason B. Franke, Molly F. TI Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis SO LANCET GLOBAL HEALTH LA English DT Article ID FOLLOW-UP; CONTROLLED-TRIAL; FIELD TRIAL; VACCINES; EFFICACY; BANGLADESH; CAMPAIGN AB Background Between April and June, 2012, a reactive cholera vaccination campaign was done in Haiti with an oral inactivated bivalent whole-cell vaccine. We aimed to assess the effectiveness of the vaccine in a case-control study and to assess the likelihood of bias in that study in a bias-indicator study. Methods Residents of Bocozel or Grand Saline who were eligible for the vaccination campaign (ie, age >= 12 months, not pregnant, and living in the region at the time of the vaccine campaign) were included. In the primary case-control study, cases had acute watery diarrhoea, sought treatment at one of three participating cholera treatment units, and had a stool sample positive for cholera by culture. For each case, four control individuals who did not seek treatment for acute watery diarrhoea were matched by location of residence, enrolment time (within 2 weeks of the case), and age (1-4 years, 5-15 years, and > 15 years). Cases in the bias-indicator study were individuals with acute watery diarrhoea with a negative stool sample for cholera. Controls were selected in the same manner as in the primary case-control study. Trained staff used standard laboratory procedures to do rapid tests and stool cultures from study cases. Participants were interviewed to collect data on sociodemographic characteristics, risk factors for cholera, and self-reported vaccination. Data were analysed by conditional logistic regression, adjusting for matching factors. Findings From Oct 24, 2012, to March 9, 2014, 114 eligible individuals presented with acute watery diarrhoea and were enrolled, 25 of whom were subsequently excluded. 47 participants were analysed as cases in the vaccine effectiveness case-control study and 42 as cases in the bias-indicator study. 33 (70%) of 47 cholera cases self-reported vaccination versus 167 (89%) of 188 controls (vaccine effectiveness 63%, 95% CI 8-85). 27 (57%) of 47 cases had certified vaccination versus 147 (78%) of 188 controls (vaccine effectiveness 58%, 13-80). Neither self-reported nor verified vaccination was significantly associated with non-cholera diarrhoea (vaccine effectiveness 18%, 95% CI -208 to 78 by self-report and -21%, -238 to 57 by verified vaccination). Interpretation Bivalent whole-cell oral cholera vaccine effectively protected against cholera in Haiti from 4 months to 24 months after vaccination. Vaccination is an important component of efforts to control cholera epidemics. Copyright (C) Ivers et al. Open Access article distributed under the terms of CC BY-NC-ND. C1 [Ivers, Louise C.; Teng, Jessica E.; Murray, Megan B.] Brigham & Womens Hosp, Dept Med, Div Global Hlth Equ, Boston, MA 02115 USA. [Ivers, Louise C.; Murray, Megan B.; Franke, Molly F.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ivers, Louise C.; Teng, Jessica E.; Murray, Megan B.; Franke, Molly F.] Partners In Hlth, Boston, MA USA. [Hilaire, Isabelle J.; Almazor, Charles P.; Jerome, J. Gregory; Ternier, Ralph] Zanmi Lasante, St Marc, Haiti. [Boncy, Jacques; Buteau, Josiane] Minist Hlth & Populat, Natl Lab, Port Au Prince, Haiti. [Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Ivers, LC (reprint author), Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. EM louise_ivers@hms.harvard.edu FU National Institutes of Health [NIAID R01 AI099243]; Delivering Oral Vaccines Effectively project at Johns Hopkins University - Bill & Melinda Gates Foundation; Global Health Research Core of the Department of Global Health and Social Medicine; American Red Cross FX These studies were supported by grants from the National Institutes of Health, (NIAID R01 AI099243; LCI, JET, JBH, and MFF), the Delivering Oral Vaccines Effectively project at Johns Hopkins University, which is funded by the Bill & Melinda Gates Foundation (LCI and JET), and the Global Health Research Core of the Department of Global Health and Social Medicine (MFF). We thank the study participants, the Ministry of Health and Population of Haiti, the Abundance Foundation, and the staff of Zanmi Lasante. We are also grateful to the American Red Cross and private donors who funded the oral cholera vaccination campaign. NR 31 TC 15 Z9 15 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD MAR PY 2015 VL 3 IS 3 BP E162 EP E168 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CB9OH UT WOS:000349960700015 PM 25701994 ER PT J AU Gagoski, BA Bilgic, B Eichner, C Bhat, H Grant, PE Wald, LL Setsompop, K AF Gagoski, Borjan A. Bilgic, Berkin Eichner, Cornelius Bhat, Himanshu Grant, P. Ellen Wald, Lawrence L. Setsompop, Kawin TI RARE/Turbo Spin Echo Imaging with Simultaneous Multislice Wave-CAIPI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE simultaneous multislice; multiband; Wave-CAIPI; MultiPINS; CAIPIRINHA; RARE; TSE; FSE ID PINS RADIOFREQUENCY PULSES; REFOCUSING FLIP ANGLES; GRASE GRADIENT-ECHO; ARBITRARY K-SPACE; WHOLE-BRAIN; FAST MRI; DIFFUSION MRI; PARALLEL MRI; RF PULSES; SENSE AB PurposeTo enable highly accelerated RARE/Turbo Spin Echo (TSE) imaging using Simultaneous MultiSlice (SMS) Wave-CAIPI acquisition with reduced g-factor penalty. MethodsSMS Wave-CAIPI incurs slice shifts across simultaneously excited slices while playing sinusoidal gradient waveforms during the readout of each encoding line. This results in an efficient k-space coverage that spreads aliasing in all three dimensions to fully harness the encoding power of coil sensitivities. The novel MultiPINS radiofrequency (RF) pulses dramatically reduce the power deposition of multiband (MB) refocusing pulse, thus allowing high MB factors within the Specific Absorption Rate (SAR) limit. ResultsWave-CAIPI acquisition with MultiPINS permits whole brain coverage with 1 mm isotropic resolution in 70 s at effective MB factor 13, with maximum and average g-factor penalties of g(max)=1.34 and g(avg)=1.12, and without R penalty. With blipped-CAIPI, the g-factor performance was degraded to g(max)=3.24 and g(avg)=1.42; a 2.4-fold increase in g(max) relative to Wave-CAIPI. At this MB factor, the SAR of the MultiBand and PINS pulses are 4.2 and 1.9 times that of the MultiPINS pulse, while the peak RF power are 19.4 and 3.9 times higher. ConclusionCombination of the two technologies, Wave-CAIPI and MultiPINS pulse, enables highly accelerated RARE/TSE imaging with low SNR penalty at reduced SAR. Magn Reson Med, 2015. (c) 2015 Wiley Periodicals, Inc. Magn Reson Med 73:929-938, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Gagoski, Borjan A.; Grant, P. Ellen] Boston Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. [Gagoski, Borjan A.; Bilgic, Berkin; Grant, P. Ellen; Wald, Lawrence L.; Setsompop, Kawin] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Bilgic, Berkin; Eichner, Cornelius; Wald, Lawrence L.; Setsompop, Kawin] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Eichner, Cornelius] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany. [Bhat, Himanshu] Siemens Med Solut USA Inc, Charlestown, MA USA. [Wald, Lawrence L.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. RP Gagoski, BA (reprint author), 1 Autumn St,AU457, Boston, MA 02215 USA. EM borjan.gagoski@childrens.harvard.edu RI Wald, Lawrence/D-4151-2009 FU NIH [R00EB012107, P41RR14075, R01EB017337]; NIH Blueprint for Neuroscience [1U01MH093765] FX Grant sponsor: NIH; Grant numbers: R00EB012107; P41RR14075; R01EB017337; Grant sponsor: NIH Blueprint for Neuroscience; Grant number: 1U01MH093765 (Human Connectome Project). NR 56 TC 3 Z9 3 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAR PY 2015 VL 73 IS 3 BP 929 EP 938 DI 10.1002/mrm.25615 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CC3VV UT WOS:000350279900005 PM 25640187 ER PT J AU Cauley, SF Xi, YZ Bilgic, B Xia, JL Adalsteinsson, E Balakrishnan, V Wald, LL Setsompop, K AF Cauley, Stephen F. Xi, Yuanzhe Bilgic, Berkin Xia, Jianlin Adalsteinsson, Elfar Balakrishnan, Venkataramanan Wald, Lawrence L. Setsompop, Kawin TI Fast Reconstruction for Multichannel Compressed Sensing Using a Hierarchically Semiseparable Solver SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE parallel imaging; compressed sensing; SENSE; hierarchically semiseparable ID IMAGING RECONSTRUCTION; MRI; GRAPPA AB PurposeThe adoption of multichannel compressed sensing (CS) for clinical magnetic resonance imaging (MRI) hinges on the ability to accurately reconstruct images from an undersampled dataset in a reasonable time frame. When CS is combined with SENSE parallel imaging, reconstruction can be computationally intensive. As an alternative to iterative methods that repetitively evaluate a forward CS+SENSE model, we introduce a technique for the fast computation of a compact inverse model solution. MethodsA recently proposed hierarchically semiseparable (HSS) solver is used to compactly represent the inverse of the CS+SENSE encoding matrix to a high level of accuracy. To investigate the computational efficiency of the proposed HSS-Inverse method, we compare reconstruction time with the current state-of-the-art. In vivo 3T brain data at multiple image contrasts, resolutions, acceleration factors, and number of receive channels were used for this comparison. ResultsThe HSS-Inverse method allows for >6x speedup when compared to current state-of-the-art reconstruction methods with the same accuracy. Efficient computational scaling is demonstrated for CS+SENSE with respect to image size. The HSS-Inverse method is also shown to have minimal dependency on the number of parallel imaging channels/acceleration factor. ConclusionsThe proposed HSS-Inverse method is highly efficient and should enable real-time CS reconstruction on standard MRI vendors' computational hardware. Magn Reson Med 73:1034-1040, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Cauley, Stephen F.; Bilgic, Berkin; Adalsteinsson, Elfar; Wald, Lawrence L.; Setsompop, Kawin] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Xi, Yuanzhe; Xia, Jianlin] Purdue Univ, Dept Math, W Lafayette, IN 47907 USA. [Bilgic, Berkin; Wald, Lawrence L.; Setsompop, Kawin] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Adalsteinsson, Elfar; Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Balakrishnan, Venkataramanan] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. RP Cauley, SF (reprint author), MGH Martinos Ctr Biomed Imaging, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM stcauley@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 FU NIH [U01MH093765]; NIBIB [R00EB012107, R01EB006847]; NCRR [P41RR014075]; NSF [DMS-1255416, DMS-1115572, CHE-0957024] FX Grant sponsor: NIH; Grant number: U01MH093765; Grant sponsor: NIBIB; Grant numbers: R00EB012107; R01EB006847; Grant sponsor: NCRR; Grant number: P41RR014075; Grant sponsor: NSF; Grant numbers: DMS-1255416; DMS-1115572; CHE-0957024. NR 18 TC 8 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAR PY 2015 VL 73 IS 3 BP 1034 EP 1040 DI 10.1002/mrm.25222 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CC3VV UT WOS:000350279900015 PM 24639238 ER PT J AU Guerin, B Gebhardt, M Serano, P Adalsteinsson, E Hamm, M Pfeuffer, J Nistler, J Wald, LL AF Guerin, Bastien Gebhardt, Matthias Serano, Peter Adalsteinsson, Elfar Hamm, Michael Pfeuffer, Josef Nistler, Juergen Wald, Lawrence L. TI Comparison of Simulated Parallel Transmit Body Arrays at 3 T Using Excitation Uniformity, Global SAR, Local SAR, and Power Efficiency Metrics SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE Local SAR; global SAR; power; parallel transmission; pTx coils; excitation fidelity; spokes ID ABSORPTION RATE; PULSE DESIGN; 8 CHANNELS; COIL; MRI; OPTIMIZATION; TESLA AB PurposeWe compare the performance of eight parallel transmit (pTx) body arrays with up to 32 channels and a standard birdcage design. Excitation uniformity, local specific absorption rate (SAR), global SAR, and power metrics are analyzed in the torso at 3 T for radiofrequency (RF)-shimming and 2-spoke excitations. MethodsWe used a fast cosimulation strategy for field calculation in the presence of coupling between transmit channels. We designed spoke pulses using magnitude least squares optimization with explicit constraint of SAR and power and compared the performance of the different pTx coils using the L-curve method. ResultsPTx arrays outperformed the conventional birdcage coil in all metrics except peak and average power efficiency. The presence of coupling exacerbated this power efficiency problem. At constant excitation fidelity, the pTx array with 24 channels arranged in three z-rows could decrease local SAR more than 4-fold (2-fold) for RF-shimming (2-spoke) compared to the birdcage coil for pulses of equal duration. Multi-row pTx coils had a marked performance advantage compared to single row designs, especially for coronal imaging. ConclusionPTx coils can simultaneously improve the excitation uniformity and reduce SAR compared to a birdcage coil when SAR metrics are explicitly constrained in the pulse design. Magn Reson Med 73:1137-1150, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Guerin, Bastien; Serano, Peter; Wald, Lawrence L.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Gebhardt, Matthias; Hamm, Michael; Pfeuffer, Josef; Nistler, Juergen] Siemens Healthcare, Erlangen, Germany. [Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Adalsteinsson, Elfar; Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Guerin, B (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM guerin@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 FU NIH [R01EB0068547, R01EB007942, P41EB015896]; Siemens-MIT Alliance MKI (MIT Kavli Institute for Astrophysics and Space Research) Support FX Grant sponsor: NIH; Grant numbers: R01EB0068547, R01EB007942, and P41EB015896; Grant sponsor: Siemens-MIT Alliance MKI (MIT Kavli Institute for Astrophysics and Space Research) Support. NR 37 TC 15 Z9 15 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAR PY 2015 VL 73 IS 3 BP 1137 EP 1150 DI 10.1002/mrm.25243 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CC3VV UT WOS:000350279900026 PM 24752979 ER PT J AU Lin, LP Sabnis, AJ Chan, E Olivas, V Cade, L Pazarentzos, E Asthana, S Neel, D Yan, JJ Lu, XY Pham, L Wang, MXM Karachaliou, N Cao, MG Manzano, JL Ramirez, JL Torres, JMS Buttitta, F Rudin, CM Collisson, EA Algazi, A Robinson, E Osman, I Munoz-Couselo, E Cortes, J Frederick, DT Cooper, ZA McMahon, M Marchetti, A Rosell, R Flaherty, KT Wargo, JA Bivona, TG AF Lin, Luping Sabnis, Amit J. Chan, Elton Olivas, Victor Cade, Lindsay Pazarentzos, Evangelos Asthana, Saurabh Neel, Dana Yan, Jenny Jiacheng Lu, Xinyuan Pham, Luu Wang, Mingxue M. Karachaliou, Niki Gonzalez Cao, Maria Luis Manzano, Jose Luis Ramirez, Jose Sanchez Torres, Jose Miguel Buttitta, Fiamma Rudin, Charles M. Collisson, Eric A. Algazi, Alain Robinson, Eric Osman, Iman Munoz-Couselo, Eva Cortes, Javier Frederick, Dennie T. Cooper, Zachary A. McMahon, Martin Marchetti, Antonio Rosell, Rafael Flaherty, Keith T. Wargo, Jennifer A. Bivona, Trever G. TI The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies SO NATURE GENETICS LA English DT Article ID CELL LUNG-CANCER; SIGNALING PATHWAY; COLON-CANCER; INHIBITION; BRAF; MELANOMA; KRAS; SURVIVAL; TRANSCRIPTION; ACTIVATION AB Resistance to RAF-and MEK-targeted therapy is a major clinical challenge(1-4). RAF and MEK inhibitors are initially but only transiently effective in some but not all patients with BRAF gene mutation and are largely ineffective in those with RAS gene mutation because of resistance(5-14). Through a genetic screen in BRAF-mutant tumor cells, we show that the Hippo pathway effector YAP (encoded by YAP1) acts as a parallel survival input to promote resistance to RAF and MEK inhibitor therapy. Combined YAP and RAF or MEK inhibition was synthetically lethal not only in several BRAF-mutant tumor types but also in RAS-mutant tumors. Increased YAP in tumors harboring BRAF V600E was a biomarker of worse initial response to RAF and MEK inhibition in patients, establishing the clinical relevance of our findings. Our data identify YAP as a new mechanism of resistance to RAF-and MEK-targeted therapy. The findings unveil the synthetic lethality of combined suppression of YAP and RAF or MEK as a promising strategy to enhance treatment response and patient survival. C1 [Lin, Luping; Sabnis, Amit J.; Chan, Elton; Olivas, Victor; Cade, Lindsay; Pazarentzos, Evangelos; Asthana, Saurabh; Neel, Dana; Yan, Jenny Jiacheng; Lu, Xinyuan; Pham, Luu; Wang, Mingxue M.; Collisson, Eric A.; Algazi, Alain; Bivona, Trever G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Lin, Luping; Sabnis, Amit J.; Chan, Elton; Olivas, Victor; Cade, Lindsay; Pazarentzos, Evangelos; Asthana, Saurabh; Neel, Dana; Yan, Jenny Jiacheng; Lu, Xinyuan; Pham, Luu; Wang, Mingxue M.; Collisson, Eric A.; Algazi, Alain; McMahon, Martin; Bivona, Trever G.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Sabnis, Amit J.] Univ Calif San Francisco, Dept Pediat, Div Pediat Hematol & Oncol, San Francisco, CA USA. [Karachaliou, Niki; Gonzalez Cao, Maria; Rosell, Rafael] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Canc Biol & Precis Med Program, Badalona, Spain. [Luis Manzano, Jose] Hosp Badalona Germans Trias & Pujol, Calalan Inst Oncol, Med Oncol Serv, Badalona, Spain. [Luis Ramirez, Jose] Hosp Badalona Germans Trias & Pujol, Fundacio Inst Recerca Germans Trias & Pujol IGTP, Translat Oncol Lab, Catalan Inst Oncol, Barcelona, Spain. [Sanchez Torres, Jose Miguel] Hosp Univ La Princess, Med Oncol Serv, Madrid, Spain. [Buttitta, Fiamma] Univ Fdn, Ctr Predict Mol Med, Chieti, Italy. [Rudin, Charles M.] Mem Sloan Kettering Canc Ctr, Mol Chem & Pharmacol Program, New York, NY 10021 USA. [Rudin, Charles M.] Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, New York, NY 10021 USA. [Robinson, Eric; Osman, Iman] NYU, Inst Canc, Ronald O Perelman Dept Dermatol Med & Urol, New York, NY USA. [Munoz-Couselo, Eva; Cortes, Javier] Vall dHebron Inst Oncol, Barcelona, Spain. [Frederick, Dennie T.; Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Frederick, Dennie T.; Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Comprehens Canc, Boston, MA 02114 USA. [Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. RP Bivona, TG (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM tbivona@medicine.ucsf.edu OI Pazarentzos, Evangelos/0000-0002-5453-1646; Rudin, Charles/0000-0001-5204-3465; Cooper, Zachary/0000-0003-1059-0940 FU US National Institutes of Health (NIH) Director's New Innovator Award [DP2CA174497]; Howard Hughes Medical Institute; Doris Duke Charitable Foundation; American Lung Association; National Lung Cancer Partnership; Addario Foundation; Van Auken Private Foundation; Sidney Kimmel Foundation for Cancer Research; Searle Scholars Program; La Caixa Foundation; US NIH [R01CA131261] FX We thank G. Bollag and P. Lin (Plexxikon) for providing PLX4720. We thank J. Weissman and members of the Bivona laboratory for critical review of the manuscript. The authors acknowledge funding support (to T.G.B.) from the following sources: US National Institutes of Health (NIH) Director's New Innovator Award (DP2CA174497), the Howard Hughes Medical Institute (Collaborative Innovation Award), the Doris Duke Charitable Foundation, the American Lung Association, the National Lung Cancer Partnership, the Addario and Van Auken Private Foundations, the Sidney Kimmel Foundation for Cancer Research and the Searle Scholars Program. The authors also acknowledge funding from La Caixa Foundation (to R.R.) and from US NIH grant R01CA131261 (to M.M.). NR 37 TC 67 Z9 67 U1 2 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAR PY 2015 VL 47 IS 3 BP 250 EP + DI 10.1038/ng.3218 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CC4MQ UT WOS:000350327900016 PM 25665005 ER PT J AU Loh, PR Tucker, G Bulik-Sullivan, BK Vilhjalmsson, BJ Finucane, HK Salem, RM Chasman, DI Ridker, PM Neale, BM Berger, B Patterson, N Price, AL AF Loh, Po-Ru Tucker, George Bulik-Sullivan, Brendan K. Vilhjalmsson, Bjarni J. Finucane, Hilary K. Salem, Rany M. Chasman, Daniel I. Ridker, Paul M. Neale, Benjamin M. Berger, Bonnie Patterson, Nick Price, Alkes L. TI Efficient Bayesian mixed-model analysis increases association power in large cohorts SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; COMPLEX TRAITS; STRUCTURED POPULATIONS; GENETIC ASSOCIATION; COMMON SNPS; PREDICTION; STRATIFICATION; REGRESSION; ALGORITHM; INFERENCE AB Linear mixed models are a powerful statistical tool for identifying genetic associations and avoiding confounding. However, existing methods are computationally intractable in large cohorts and may not optimize power. All existing methods require time cost O(MN2) (where N is the number of samples and M is the number of SNPs) and implicitly assume an infinitesimal genetic architecture in which effect sizes are normally distributed, which can limit power. Here we present a far more efficient mixed-model association method, BOLT-LMM, which requires only a small number of O(MN) time iterations and increases power by modeling more realistic, non-infinitesimal genetic architectures via a Bayesian mixture prior on marker effect sizes. We applied BOLT-LMM to 9 quantitative traits in 23,294 samples from the Women's Genome Health Study (WGHS) and observed significant increases in power, consistent with simulations. Theory and simulations show that the boost in power increases with cohort size, making BOLT-LMM appealing for genome-wide association studies in large cohorts. C1 [Loh, Po-Ru; Tucker, George; Vilhjalmsson, Bjarni J.; Price, Alkes L.] Harvard IH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Loh, Po-Ru; Bulik-Sullivan, Brendan K.; Vilhjalmsson, Bjarni J.; Salem, Rany M.; Neale, Benjamin M.; Patterson, Nick; Price, Alkes L.] Broad Inst Harvard & MIT, Progrram Med & Populat Genet, Cambridge, MA USA. [Tucker, George; Finucane, Hilary K.; Berger, Bonnie] MIT, Dept Math, Cambridge, MA 02139 USA. [Tucker, George; Berger, Bonnie] Comp Sci & Artificial Intelligence Lab, Cambridge, MA USA. [Bulik-Sullivan, Brendan K.; Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Salem, Rany M.] Childrens Hosp Boston, Dept Endocrinol, Boston, MA USA. [Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Price, Alkes L.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Loh, PR (reprint author), Harvard IH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM loh@hsph.harvard.edu; aprice@hsph.harvard.edu RI Vilhjalmsson, Bjarni/K-3971-2014 OI Vilhjalmsson, Bjarni/0000-0003-2277-9249 FU US National Institutes of Health [R01 HG006399]; US National Institutes of Health fellowship [F32 HG007805]; Fannie and John Hertz Foundation; National Heart, Lung, and Blood Institute [HL043851, HL080467]; National Cancer Institute [CA047988]; Donald W. Reynolds Foundation; Fondation Leducq; Amgen FX We are grateful to M. Lipson, S. Simmons, A. Gusev, K. Galinsky, J. Yang, P. Visscher, Z. Zhu and D. Gudbjartsson for helpful discussions. This research was supported by US National Institutes of Health grant R01 HG006399 and US National Institutes of Health fellowship F32 HG007805. H.K.F. was supported by the Fannie and John Hertz Foundation. The WGHS is supported by HL043851 and grants HL080467 from the National Heart, Lung, and Blood Institute and grant CA047988 from the National Cancer Institute, by the Donald W. Reynolds Foundation and by the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. NR 48 TC 37 Z9 39 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAR PY 2015 VL 47 IS 3 BP 284 EP + DI 10.1038/ng.3190 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CC4MQ UT WOS:000350327900022 PM 25642633 ER PT J AU Bulik-Sullivan, BK Loh, PR Finucane, HK Ripke, S Yang, J Patterson, N Daly, MJ Price, AL Neale, BM AF Bulik-Sullivan, Brendan K. Loh, Po-Ru Finucane, Hilary K. Ripke, Stephan Yang, Jian Patterson, Nick Daly, Mark J. Price, Alkes L. Neale, Benjamin M. CA Schizophrenia Working Grp TI LD Score regression distinguishes confounding from polygenicity in genome-wide association studies SO NATURE GENETICS LA English DT Article ID MAJOR DEPRESSIVE DISORDER; BODY-MASS INDEX; GENETIC-VARIANTS; LINKAGE DISEQUILIBRIUM; IDENTIFIES 13; RISK LOCI; METAANALYSIS; POPULATIONS; DISEASE; TRAITS AB Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size. C1 [Bulik-Sullivan, Brendan K.; Loh, Po-Ru; Patterson, Nick; Daly, Mark J.; Price, Alkes L.; Neale, Benjamin M.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Bulik-Sullivan, Brendan K.; Ripke, Stephan; Daly, Mark J.; Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Bulik-Sullivan, Brendan K.; Ripke, Stephan; Daly, Mark J.; Neale, Benjamin M.] Harvard Univ, Sch Med, Boston, MA USA. [Bulik-Sullivan, Brendan K.; Ripke, Stephan; Daly, Mark J.; Neale, Benjamin M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Loh, Po-Ru; Finucane, Hilary K.; Price, Alkes L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Finucane, Hilary K.] MIT, Dept Math, Cambridge, MA 02139 USA. [Yang, Jian] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Price, Alkes L.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Neale, BM (reprint author), Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM bneale@broadinstitute.org RI Stroup, Thomas/F-9188-2014; Domenici, Enrico/K-8194-2016; Ruderfer, Douglas/M-5795-2016; McQuillin, Andrew/C-1623-2008; Slominsky, Petr/B-4640-2016; Catts, Stanley/G-6917-2013; So, Hon-Cheong/I-1100-2016; Pantelis, Christos/H-7722-2014; Yang, Jian/A-5852-2010; Melle, Ingrid /B-4858-2011; Webb, Bradley/B-1459-2009; Hansen, Thomas/O-5965-2014; Hammer, Christian/C-5827-2014; Zai, Clement/G-7379-2015; SCHALL, ULRICH/G-7452-2013; Collier, David/D-1649-2011; Mattheisen, Manuel/B-4949-2012 OI Knight, Joanne/0000-0002-7148-1660; McIntosh, Andrew/0000-0002-0198-4588; Dinan, Timothy/0000-0002-2316-7220; /0000-0002-8114-7615; Adolfsson, Rolf/0000-0001-9785-8473; Jonsson, Erik/0000-0001-8368-6332; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; murray, robin/0000-0003-0829-0519; Visscher, Peter/0000-0002-2143-8760; Stroup, Thomas/0000-0002-3123-0672; Myin-Germeys, Inez/0000-0002-3731-4930; Esko, Tonu/0000-0003-1982-6569; Murphy, Kieran/0000-0003-2930-4465; Julia Cano, Antonio/0000-0001-6064-3620; Moran, Jennifer/0000-0002-5664-4716; Walters, James/0000-0002-6980-4053; Buxbaum, Joseph/0000-0001-8898-8313; Bruggeman, Richard/0000-0002-3238-8471; O'Neill, Francis Anthony/0000-0002-7531-7657; Domenici, Enrico/0000-0001-7436-6919; Ruderfer, Douglas/0000-0002-2365-386X; McQuillin, Andrew/0000-0003-1567-2240; Bergen, Sarah/0000-0002-5888-0034; Golimbet, Vera/0000-0002-0114-4300; Stefansson, Hreinn/0000-0002-9331-6666; Agartz, Ingrid/0000-0002-9839-5391; Escott-Price, Valentina/0000-0003-1784-5483; Corvin, Aiden/0000-0001-6717-4089; Golimbet, Vera/0000-0002-9960-7114; Crowley, James/0000-0001-9051-1557; Slominsky, Petr/0000-0003-3530-0655; Pantelis, Christos/0000-0002-9565-0238; Yang, Jian/0000-0003-2001-2474; Melle, Ingrid /0000-0002-9783-548X; Webb, Bradley/0000-0002-0576-5366; Hansen, Thomas/0000-0001-6703-7762; Hammer, Christian/0000-0003-4548-7548; Collier, David/0000-0003-4087-1559; Mattheisen, Manuel/0000-0002-8442-493X FU US National Institutes of Health [F32 HG007805, R01 HG006399, R03 CA173785, R01 MH094421]; Fannie and John Hertz Foundation FX We would like to thank P. Sullivan for helpful discussion. This work was supported by US National Institutes of Health grants F32 HG007805 (P.-R.L.), R01 HG006399 (A.L.P.), R03 CA173785 (H.K.F.) and R01 MH094421 (PGC) and by the Fannie and John Hertz Foundation (H.K.F.). Data on coronary artery disease and myocardial infarction were contributed by CARDIoGRAMplusC4D investigators and were downloaded from Psychiatric Genomics Consortium. NR 43 TC 125 Z9 127 U1 8 U2 59 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAR PY 2015 VL 47 IS 3 BP 291 EP + DI 10.1038/ng.3211 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CC4MQ UT WOS:000350327900023 PM 25642630 ER PT J AU Greenlee, H Zick, SM Rosenthal, D Cohen, L Cassileth, B Tripathy, D AF Greenlee, Heather Zick, Suzanna M. Rosenthal, David Cohen, Lorenzo Cassileth, Barrie Tripathy, Debu TI Integrative oncology - strong science is needed for better patient care SO NATURE REVIEWS CANCER LA English DT Letter ID CANCER SURVIVORS; BREAST-CANCER; DISCONTINUATION C1 [Greenlee, Heather] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Zick, Suzanna M.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. [Rosenthal, David] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rosenthal, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cohen, Lorenzo] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol & Behav Sci, Houston, TX 77030 USA. [Cassileth, Barrie] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Tripathy, Debu] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. RP Greenlee, H (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. EM hg2120@columbia.edu NR 10 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAR PY 2015 VL 15 IS 3 DI 10.1038/nrc3822-c1 PG 1 WC Oncology SC Oncology GA CC4BQ UT WOS:000350296100008 PM 25693833 ER PT J AU Caroff, SN Campbell, EC AF Caroff, Stanley N. Campbell, E. Cabrina TI Risk of neuroleptic malignant syndrome in patients with NMDAR encephalitis SO NEUROLOGICAL SCIENCES LA English DT Letter DE Neuroleptic malignant syndrome; Encephalitis; Neuroleptics; Antipsychotics; Psychosis C1 [Caroff, Stanley N.; Campbell, E. Cabrina] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Caroff, Stanley N.; Campbell, E. Cabrina] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Caroff, SN (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM stanley.caroff@va.gov NR 5 TC 3 Z9 3 U1 0 U2 3 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 MAR PY 2015 VL 36 IS 3 BP 479 EP 480 DI 10.1007/s10072-014-2022-z PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CC4ZG UT WOS:000350365000021 PM 25480349 ER PT J AU Jones, PS Cahill, DP Brastianos, PK Flaherty, KT Curry, WT AF Jones, Pamela S. Cahill, Daniel P. Brastianos, Priscilla K. Flaherty, Keith T. Curry, William T. TI Ipilimumab and craniotomy in patients with melanoma and brain metastases: a case series SO NEUROSURGICAL FOCUS LA English DT Article DE ipilimumab; melanoma; immunotherapy; craniotomy; metastases ID LONG-TERM SURVIVAL; PHASE-2 TRIAL; MALIGNANT-MELANOMA; CTLA-4 BLOCKADE; OPEN-LABEL; THERAPY; IMMUNOTHERAPY; VEMURAFENIB; MANAGEMENT; ANTIBODY AB OBJECT In patients with large or symptomatic brain lesions from metastatic melanoma, the value of resection of metastases to facilitate administration of systemic ipilimumab therapy has not yet been described. The authors undertook this study to investigate whether craniotomy creates the opportunity for patients to receive and benefit from ipilimumab who would otherwise succumb to brain metastasis prior to the onset of regression. METHODS All patients with metastatic melanoma who received ipilimumab and underwent craniotomy for metastasis resection between 2008 and 2014 at the Massachusetts General Hospital were identified through retrospective chart review. The final analysis included cases involving patients who underwent craniotomy within 3 months prior to initiation of therapy or up to 6 months after cessation of ipilimumab administration. RESULTS Twelve patients met the inclusion criteria based on timing of therapy (median age 59.2). The median number of metastases at the time of craniotomy was 2. The median number of ipilimumab doses received was 4. Eleven of 12 courses of ipilimumab were stopped for disease progression, and 1 was stopped for treatment-induced colitis. Eight of 12 patients had improvement in their performance status following craniotomy. Of the 6 patients requiring corticosteroids prior to craniotomy, 3 tolerated corticosteroid dose reduction after surgery. Ten of 12 patients had died by the time of data collection, with 1 patient lost to follow-up. The median survival after the start of ipilimumab treatment was 7 months. CONCLUSIONS In this series, patients who underwent resection of brain metastases in temporal proximity to receiving ipilimumab had qualitatively improved performance status following surgery in most cases. Surgery facilitated corticosteroid reduction in select patients. Larger analyses are required to better understand possible synergies between craniotomy for melanoma metastases and ipilimumab treatment. C1 [Jones, Pamela S.; Cahill, Daniel P.; Curry, William T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Brastianos, Priscilla K.; Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Curry, WT (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Stephen E & Catherine Pappas Ctr Neurooncol, 55 Fruit St,YAW 9E-9026, Boston, MA 02114 USA. EM wcurry@mgh.harvard.edu OI Brastianos, Priscilla/0000-0003-4470-8425; Cahill, Daniel/0000-0003-2552-6546 NR 27 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD MAR PY 2015 VL 38 IS 3 AR E5 DI 10.3171/2014.12.FOCUS14698 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CC5SI UT WOS:000350422600003 PM 25727227 ER PT J AU Pownall, HJ Bray, GA Wagenknecht, LE Walkup, MP Heshka, S Hubbard, VS Hill, J Kahn, SE Nathan, DM Schwartz, AV Johnson, KC AF Pownall, Henry J. Bray, George A. Wagenknecht, Lynne E. Walkup, Michael P. Heshka, Stanley Hubbard, Van S. Hill, James Kahn, Steven E. Nathan, David M. Schwartz, Anne V. Johnson, Karen C. TI Changes in Body Composition Over 8 Years in a Randomized Trial of a Lifestyle Intervention: The Look AHEAD Study SO OBESITY LA English DT Article ID TYPE-2 DIABETES-MELLITUS; X-RAY ABSORPTIOMETRY; DISEASE RISK-FACTORS; WEIGHT-LOSS; CARDIOVASCULAR-DISEASE; FAT DISTRIBUTION; GENERAL-POPULATION; INSULIN-RESISTANCE; OLDER-ADULTS; OBESE WOMEN AB ObjectiveTo determine the effects of an intensive lifestyle intervention versus a comparison group on body composition in obese or overweight persons with type 2 diabetes at baseline and at 1, 4, and 8 years. MethodsBody composition was measured by dual-energy X-ray absorptiometry in a subset of 1019 Look AHEAD study volunteers randomized to intervention or comparison groups. The intervention was designed to achieve and maintain 7% weight loss through increased physical activity and reduced caloric intake. The comparison group received social support and diabetes education. ResultsAt 1 year, the intervention group lost fat (5.60.2 kg) and lean mass (2.3 +/- 0.1 kg) but regained fat (approximate to 100%) and lost lean mass between years 1 and 8. Between baseline and year 8, weight loss was greater in intervention versus comparison groups (4.0 +/- 0.4 vs. 2.3 +/- 0.4 kg); comparison group weight loss was mostly lean mass (2.1 +/- 0.17 kg). Fat mass in the intervention group was lower than that of the comparison group at all post-baseline time points. ConclusionsReduced fat mass may place the intervention group at a lower risk of obesity-linked sequelae, a hypothesis that can be tested by future studies of this cohort. C1 [Pownall, Henry J.] Houston Methodist Res Inst, Div Atherosclerosis, Dept Cardiol, Houston, TX USA. [Pownall, Henry J.] Baylor Coll Med, Houston, TX 77030 USA. [Bray, George A.] Pennington Biomed Res Ctr, Div Clin Obes, Baton Rouge, LA 70808 USA. [Wagenknecht, Lynne E.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Walkup, Michael P.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Heshka, Stanley] St Lukes Roosevelt Hosp, Dept Med, New York, NY 10025 USA. [Hubbard, Van S.] NIH, Bethesda, MD 20892 USA. [Hill, James] Univ Colorado, Anschutz Hlth & Wellness Ctr, Denver, CO 80202 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Schwartz, Anne V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. RP Wagenknecht, LE (reprint author), Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. EM lwgnkcht@wakehealth.edu OI Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health (NIH) through National Institute of Diabetes and Digestive and Kidney Diseases [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women's Health; Centers for Disease Control and Prevention; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center; Massachusetts Institute of Technology General Clinical Research Center [M01RR01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee at Memphis General Clinical Research Center [M01RR0021140]; University of Pittsburgh General Clinical Research Center (GCRC) [M01RR000056]; Clinical Translational Research Center (CTRC) - Clinical & Translational Science Award [UL1 RR 024153]; NIH [DK 046204]; VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; Frederic C. Bartter General Clinical Research Center [M01RR01346] FX This research was supported by the National Institutes of Health (NIH) through cooperative agreements with the National Institute of Diabetes and Digestive and Kidney Diseases: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. Additional funding was provided by the National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women's Health; the Centers for Disease Control and Prevention; and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (I.H.S.) provided personnel, medical oversight, and use of facilities. Additional support provided by The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (GCRC) (M01RR000056), the Clinical Translational Research Center (CTRC) funded by the Clinical & Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and the Frederic C. Bartter General Clinical Research Center (M01RR01346). The following organizations have committed to make major contributions to Look AHEAD: FedEx Corporation; Health Management Resources; LifeScan, Inc., a Johnson & Johnson Company; OPTIFAST (R) of Nestle HealthCare Nutrition, Inc.; Hoffmann-La Roche Inc.; Abbott Nutrition; and Slim-Fast Brand of Unilever North America. Some of the information contained herein was derived from data provided by the Bureau of Vital Statistics, New York City Department of Health and Mental Hygiene. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of the funding sources. NR 40 TC 8 Z9 8 U1 1 U2 16 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 MAR PY 2015 VL 23 IS 3 BP 565 EP 572 DI 10.1002/oby.21005 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CC3LG UT WOS:000350249700011 PM 25707379 ER PT J AU Sakallioglu, EE Sakallioglu, U Lutfioglu, M Pamuk, F Kantarci, A AF Sakallioglu, E. E. Sakallioglu, U. Lutfioglu, M. Pamuk, F. Kantarci, A. TI Vascular endothelial cadherin and vascular endothelial growth factor in periodontitis and smoking SO ORAL DISEASES LA English DT Article DE VE-cadherin; VEGF; smoking; periodontitis; gingival crevicular fluid ID GINGIVAL CREVICULAR FLUID; C-REACTIVE PROTEIN; VE-CADHERIN; TYROSINE PHOSPHORYLATION; ADHERENS JUNCTIONS; CIGARETTE-SMOKING; OXIDATIVE STRESS; SMALL AIRWAYS; BLOOD-FLOW; IN-VIVO AB OBJECTIVE: This study investigated the vascularization in periodontal disease process via revealing: (i) vascular endothelial cadherin (VE-cadherin) and vascular endothelial growth factor (VEGF) productions in periodontitis and (ii) the impact of smoking on this phenomenon. MATERIALS AND METHODS: Fifteen smokers and 15 non-smokers with/without periodontitis were allocated by split-mouth randomization regarding their smoking and periodontal statuses. The teeth with periodontitis in smokers (group 1), without periodontitis in smokers (group 2), with periodontitis in non-smokers (group 3), and without periodontitis in non-smokers (group 4) constituted the study groups. Gingival crevicular fluid (GCF) levels of VE-cadherin and VEGF were determined by ELISA to evaluate their profiles in the groups. RESULTS: There were increased VE-cadherin levels in groups 1 and 3 compared with groups 2 and 4 (P < 0.05). Group 2 demonstrated higher VE-cadherin level than group 4 (P < 0.05). Increased VEGF was noted in groups 1 and 3 compared with groups 2 and 4 (P < 0.05) with similar levels between groups 1 and 3 and groups 2 and 4 (P > 0.05). There were no correlations between the VE-cadherin and VEGF levels in all groups (P > 0.05). CONCLUSION: The results suggest that VE-cadherin and VEGF may increase in periodontitis, and smoking may uniquely cause VE-cadherin production in GCF. C1 [Sakallioglu, E. E.; Sakallioglu, U.; Lutfioglu, M.] Ondokuz Mayis Univ, Fac Dent, Dept Periodontol, TR-55139 Kurupelit, Samsun, Turkey. [Pamuk, F.] Aydin Univ, Fac Dent, Dept Periodontol, Istanbul, Turkey. [Kantarci, A.] Forsyth Inst, Dept Periodontol, Cambridge, MA USA. RP Sakallioglu, EE (reprint author), Ondokuz Mayis Univ, Fac Dent, Dept Periodontol, TR-55139 Kurupelit, Samsun, Turkey. EM eseracarel@hotmail.com NR 55 TC 2 Z9 2 U1 4 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X EI 1601-0825 J9 ORAL DIS JI Oral Dis. PD MAR PY 2015 VL 21 IS 2 BP 263 EP 269 DI 10.1111/odi.12261 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CB9XC UT WOS:000349986500017 PM 24853861 ER PT J AU Puram, SV Yarlagadda, BB Sethi, R Muralidhar, V Chambers, KJ Emerick, KS Rocco, JW Lin, DT Deschler, DG AF Puram, Sidharth V. Yarlagadda, Bharat B. Sethi, Rosh Muralidhar, Vinayak Chambers, Kyle J. Emerick, Kevin S. Rocco, James W. Lin, Derrick T. Deschler, Daniel G. TI Transfusion in Head and Neck Free Flap Patients: Practice Patterns and a Comparative Analysis by Flap Type SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE transfusion; free flap; head and neck cancer ID ACUTE NORMOVOLEMIC HEMODILUTION; ALLOGENEIC BLOOD-TRANSFUSION; RISK-FACTORS; SURGERY; RECONSTRUCTION; INFECTION AB Objective To characterize patterns of utilization and outcomes following transfusion in head and neck patients undergoing free flap reconstruction. Study Design Case series with chart review. Setting Tertiary academic medical center. Subjects and Methods Two hundred eighty-two head and neck patients undergoing free flap reconstruction from 2011 to 2013. Outcome parameters included post-transfusion hematocrit increase, length of stay (LOS), flap survival, and perioperative complications. Results Of all head and neck free flap patients, 48.9% received blood transfusions. Average pretransfusion hametocrit (Hct) was 24.7% 0.2% with 2.5 +/- 0.1 units of blood transfused. Transfused patients were more likely to have been taken back to the operating room. Rates of transfusion were similar between flap types, although anterolateral thigh (ALT) and fibular free flap (FFF) patients had higher transfusion requirements compared to radial forearm free flap (RFFF) patients. Further, FFF patients trended toward receiving transfusions earlier. Transfusion did not influence flap survival but was associated with wound dehiscence, myocardial infarction, congestive heart failure, respiratory distress, and pneumonia. Subset analyses by flap type revealed that differences were significant among the RFFF and FFF cohorts but not ALT patients. When comparing patients who were transfused for Hct <21 to those transfused for Hct <27, there were no differences in LOS, flap survival, or postsurgical complications. Conclusions Among the different types of flaps, FFF and ALT are associated with higher transfusion requirements. Transfusion in patients undergoing free flap reconstruction does not significantly affect flap survival but was associated with perioperative complications. Our data support consideration of a restrictive transfusion policy in free flap patients. C1 [Puram, Sidharth V.; Yarlagadda, Bharat B.; Sethi, Rosh; Muralidhar, Vinayak; Chambers, Kyle J.; Emerick, Kevin S.; Rocco, James W.; Lin, Derrick T.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Puram, Sidharth V.; Yarlagadda, Bharat B.; Sethi, Rosh; Muralidhar, Vinayak; Chambers, Kyle J.; Emerick, Kevin S.; Rocco, James W.; Lin, Derrick T.; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM daniel_deschler@meei.harvard.edu NR 20 TC 6 Z9 6 U1 0 U2 1 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 MAR PY 2015 VL 152 IS 3 BP 449 EP 457 DI 10.1177/0194599814567107 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CC6LS UT WOS:000350477100011 PM 25628368 ER PT J AU Kozin, ED Sethi, RKV Lehmann, A Remenschneider, AK Golub, JS Reyes, SA Emerick, KS Lee, DJ Gray, ST AF Kozin, Elliott D. Sethi, Rosh K. V. Lehmann, Ashton Remenschneider, Aaron K. Golub, Justin S. Reyes, Samuel A. Emerick, Kevin S. Lee, Daniel J. Gray, Stacey T. TI Analysis of an Online Match Discussion Board: Improving the Otolaryngology-Head and Neck Surgery Match SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE otolaryngology; Match; education; Internet; social media ID RESIDENT SELECTION; PROGRAM; PERFORMANCE; VIEWPOINT AB Objective The Match has become the accepted selection process for graduate medical education. Otomatch.com has provided an online forum for Otolaryngology-Head and Neck Surgery (OHNS) Match-related questions for over a decade. Herein, we aim to delineate the type of posts on Otomatch to better understand the perspective of medical students applying for OHNS residency. Study Design Retrospective review of an OHNS Match-related online forum. Subjects and Methods Subjects were contributors to an OHNS Match-related online forum. Posts on Otomatch between December 2001 and April 2014 were reviewed. The title of each thread and number of views were recorded for quantitative analysis. Each thread was organized into 1 of 6 major categories and 1 of 18 subcategories. National Resident Matching Program (NRMP) data were utilized for comparison. Results We identified 1921 threads corresponding to over 2 million page views. Over 40% of threads were related to questions about specific programs, and 27% were discussions about interviews. Views, a surrogate measure for popularity, reflected different trends. The majority of individuals viewed posts on interviews (42%), program-specific questions (20%), and how to rank programs (11%). There was an increase in viewership tracked with a rise in applicant numbers based on NRMP data. Conclusion Our study provides an in-depth analysis of a popular discussion forum for medical students interested in the OHNS Match process. The most viewed posts are about interview dates and questions regarding specific programs. We provide suggestions to address unmet needs for medical students and potentially improve the Match process. C1 [Kozin, Elliott D.; Sethi, Rosh K. V.; Lehmann, Ashton; Remenschneider, Aaron K.; Emerick, Kevin S.; Lee, Daniel J.; Gray, Stacey T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kozin, Elliott D.; Sethi, Rosh K. V.; Lehmann, Ashton; Remenschneider, Aaron K.; Emerick, Kevin S.; Lee, Daniel J.; Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Golub, Justin S.] Univ Cincinnati, Dept Otolaryngol Head & Neck Surg, Cincinnati, OH USA. [Reyes, Samuel A.] SUNY Buffalo, Dept Otolaryngol, Buffalo, NY 14260 USA. RP Gray, ST (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Stacey_Gray@meei.harvard.edu FU NIDCD NIH HHS [T32 DC000020] NR 21 TC 1 Z9 1 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 2015 VL 152 IS 3 BP 458 EP 464 DI 10.1177/0194599814561187 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CC6LS UT WOS:000350477100012 PM 25550223 ER PT J AU Raol, N Rogers, D Setlur, J Hartnick, CJ AF Raol, Nikhila Rogers, Derek Setlur, Jennifer Hartnick, Christopher J. TI Comparison of Hybrid Laryngotracheal Reconstruction to Traditional Single- and Double-Stage Laryngotracheal Reconstruction SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE laryngotracheal reconstruction; LTR; subglottic stenosis; hybrid LTR ID NEONATAL SUBGLOTTIC STENOSIS; OUTCOMES; CHILDREN; SURGERY; TRENDS AB Objectives (1) To describe outcomes from and modifications to the hybrid laryngotracheal reconstruction (LTR) technique and (2) to compare this technique to traditional single- and double-stage LTR (ssLTR/dsLTR). Study Design Chart review with case series. Setting Tertiary care otolaryngology specialty hospital. Subjects All patients under 18 years of age who underwent LTR by a single surgeon from July 1, 2009, to December 31, 2013. Methods Charts were assessed for age, gender, etiology of stenosis, type of reconstruction, comorbidities, length of stay, complications, and tracheostomy status. Analysis was performed using Kruskal-Wallis and Wilcoxon rank sum analysis. Results Forty-four patients were identified, with 13 hybrid LTRs, 27 ssLTRs, and 4 dsLTRs. Of the hybrid LTRs, an overall decannulation rate of 76.9% was noted, comparable to those for dsLTR. The hybrid LTR technique offered a significantly shorter period of narcotic use when compared to ssLTR (median 15 vs 21 days, P < .01). No patients in the hybrid LTR group developed supraglottic granulation tissue. There was no statistically significant difference in median length of stay for ssLTRs, dsLTRs, and hybrid LTRs (P = .38). Conclusion The hybrid LTR technique is well tolerated and useful in patients of all ages. Narcotics can be weaned more quickly due to the presence of a secure airway at all times via the existing tracheostomy. Use of a long stent prevents formation of granulation tissue that may be seen with a suprastomal stent. This technique should be considered in patients with high-grade stenosis with a preexisting tracheostomy. C1 [Raol, Nikhila; Rogers, Derek; Setlur, Jennifer; Hartnick, Christopher J.] Harvard Univ, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Harvard Univ, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM Christopher_hartnick@meei.harvard.edu NR 15 TC 0 Z9 0 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 MAR PY 2015 VL 152 IS 3 BP 524 EP 529 DI 10.1177/0194599814567106 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CC6LS UT WOS:000350477100023 PM 25573683 ER PT J AU Acha, MR Keaney, JJ Lubitz, SA Milan, DJ Mansour, M Heist, KE Ptaszek, LM Singh, JP Blendea, D Mela, T AF Acha, Moshe Rav Keaney, John J. Lubitz, Steven A. Milan, David J. Mansour, Moussa Heist, Kevin E. Ptaszek, Leon M. Singh, Jagmeet P. Blendea, Dan Mela, Theofanie TI Increased Perforation Risk with an MRI-Conditional Pacing Lead: A Single-Center Study SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE pacing; imaging ID ACTIVE-FIXATION LEADS; CARDIAC PERFORATION; PACEMAKER; COMPLICATIONS; IMPLANTATION AB BackgroundMagnetic resonance imaging (MRI) has been considered contraindicated in patients with cardiac pacemakers (PPMs). Recently, Medtronic (MDT) MRI SureScan PPM (Medtronic Inc., Minneapolis, MN, USA) and leads were introduced into clinical practice in the United States of America. ObjectiveTo compare MDT CapSureFix 5086 MRI SureScan lead-associated perforation and dislodgement rates with MDT non-MRI SureScan active fixation leads. MethodsWe retrospectively analyzed the records of all patients implanted with MDT CapSureFix 5086 MRI SureScan leads as well as all patients implanted with MDT 4076 and 5076 leads at our institution from April 2011 to April 2014. ResultsFour of 72 patients implanted with MDT CapSureFix 5086 MRI SureScan leads (5.5%) had evidence of lead perforation, necessitating pericardiocentesis in three cases and lead revision in one case. Three of the four perforations were delayed perforations, presenting more than 3 weeks postimplant. Two patients implanted with MDT CapSureFix 5086 MRI SureScan leads (2.8%) had lead dislodgement. Of 420 patients implanted with MDT non-MRI SureScan leads, there were two perforations (0.47%) and four dislodgements (0.9%). There were significantly increased lead perforations associated with MDT CapSureFix 5086 MRI SureScan leads (P = 0.005) and a nonsignificant trend toward increased dislodgements (P = 0.18) when compared with MDT non-MRI SureScan leads. ConclusionIn contradiction to prior studies, this retrospective study suggests an increased perforation rate with MDT CapSureFix 5086 MRI SureScan leads. Most perforations were delayed perforations, presenting more than 3 weeks postimplant. Higher volume prospective studies with longer follow-up are needed to confirm our findings. C1 [Acha, Moshe Rav; Keaney, John J.; Lubitz, Steven A.; Milan, David J.; Mansour, Moussa; Heist, Kevin E.; Ptaszek, Leon M.; Singh, Jagmeet P.; Blendea, Dan; Mela, Theofanie] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.; Milan, David J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Acha, MR (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 108, Boston, MA 02114 USA. EM ravacha.moshe@gmail.com FU St. Jude; Biosense Webster; Boston Scientific; Endosense; MC10; Voyage Medical; Securus Medical; Biotronik; Sorin FX Dr. Moshe Rav Acha-modest lecture honoraria, St. Jude; Dr. John J. Keaney-none; Dr. David J. Milan-none; Dr. Moussa Mansour-consult honoraria: Biosense Webster, St. Jude, Medtronic; research grants: St. Jude, Biosense Webster, Boston Scientific, Endosense, MC10, Voyage Medical, Securus Medical; Dr. E. Kevin Heist-modest consulting honoraria: Biosense Webster, St. Jude; research grant: Biotronik, Sorin; Dr. Leon M. Ptaszek-consulting honoraria: SJM, Mast Therapeutics; Dr. Jagmeet P. Singh-consulting and research: Medtronic, St. Jude, Biotronik, Boston Scientific, Sorin; Dr. Dan Blendea-none; Dr. Theofanie Mela-modest speaker's honoraria: Boston Scientific, Medtronic, Biotronik, St. Jude. NR 22 TC 4 Z9 4 U1 0 U2 2 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 MAR PY 2015 VL 38 IS 3 BP 334 EP 342 DI 10.1111/pace.12550 PG 9 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA CC6UZ UT WOS:000350505800009 PM 25469809 ER PT J AU Dicianno, BE Parmanto, B Fairman, AD Crytzer, TM Yu, DXH Pramana, G Coughenour, D Petrazzi, AA AF Dicianno, Brad E. Parmanto, Bambang Fairman, Andrea D. Crytzer, Theresa M. Yu, Daihua X. Pramana, Gede Coughenour, Derek Petrazzi, Alan A. TI Perspectives on the Evolution of Mobile (mHealth) Technologies and Application to Rehabilitation SO PHYSICAL THERAPY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE; SELF-MANAGEMENT; WEIGHT-LOSS; RELIABILITY; SYSTEM; INTERVENTION; VALIDITY; PROGRAM; SMARTPHONE AB Individuals with chronic conditions and disabilities who are vulnerable to secondary complications often require complex habilitative and rehabilitative services to prevent and treat these complications. This perspective article reviews the evolution of mHealth technologies and presents insights as to how this evolution informed our development of a novel mHealth system, iMHere (interactive mobile health and rehabilitation), and other technologies, including those used by the Veterans Administration. This article will explain the novel applications of In Health for rehabilitation and specifically physical therapy. Perspectives on the roles of rehabilitation professionals in the delivery of health care using mHealth systems are included. Challenges to mHealth, including regulatory and funding issues, are discussed. This article also describes how mHealth can be used to improve patient satisfaction and delivery of care and to promote health and wellness. C1 [Dicianno, Brad E.] Human Engn Res Lab, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Dicianno, Brad E.] Univ Pittsburgh, Dept Phys Med & Rehabil, Sch Med, Pittsburgh, PA 15206 USA. [Dicianno, Brad E.; Parmanto, Bambang; Yu, Daihua X.; Pramana, Gede] Univ Pittsburgh, Dept Hlth Informat Management, Sch Hlth & Rehabil Sci, Pittsburgh, PA 15206 USA. [Fairman, Andrea D.; Crytzer, Theresa M.] Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA. [Fairman, Andrea D.] Duquesne Univ, Dept Occupat Therapy, Pittsburgh, PA 15219 USA. [Coughenour, Derek] Vet Affairs Pittsburgh Healthcare Syst, Rehabil Dept, Clin Support Serv Line, Pittsburgh, PA USA. [Petrazzi, Alan A.] Vet Affairs Pittsburgh Healthcare Syst, Primary Care Serv Line, Pittsburgh, PA USA. RP Dicianno, BE (reprint author), Univ Pittsburgh, Human Engn Res Lab, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM dicianno@pitt.edu RI Emchi, Karma/Q-1952-2016 FU National Institute on Disability and Rehabilitation Research (NIDRR) [H133E090002]; Rehabilitation Engineering Research Center on Telerehabilitatiori (RERC-TR); Verizon Foundation FX This research was supported, in part, by grants from the National Institute on Disability and Rehabilitation Research (NIDRR) grant H133E090002, the Rehabilitation Engineering Research Center on Telerehabilitatiori (RERC-TR), and the Verizon Foundation. NR 72 TC 7 Z9 8 U1 5 U2 27 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 EI 1538-6724 J9 PHYS THER JI Phys. Ther. PD MAR PY 2015 VL 95 IS 3 BP 397 EP 405 DI 10.2522/ptj.20130534 PG 9 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA CC3RK UT WOS:000350266800011 PM 24925075 ER PT J AU Yulek, F Dirik, EB Eren, Y Simavli, H Ugurlu, N Cagil, N Simsek, S AF Yulek, Fatma Dirik, Ebru Bilge Eren, Yasemin Simavli, Huseyin Ugurlu, Nagihan CagIl, Nurullah Simsek, Saban TI Macula and Retinal Nerve Fiber Layer in Migraine Patients: Analysis By Spectral Domain Optic Coherence Tomography SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Ganglion cell complex thickness; macular thickness; migraine; nerve fiber layer thickness; spectral domain optical coherence tomography ID LOW-TENSION GLAUCOMA; OPEN-ANGLE GLAUCOMA; THICKNESS MEASUREMENTS; REPRODUCIBILITY; HEADACHE; ASSOCIATION; VASOSPASM; CORTEX; SCALES; BLOOD AB Aim: Investigating the retinal nerve fiber layer (RNFL), macular and ganglion cell complex thickness in eyes of migraine patients using optical coherence tomography. Methods: The study was designed as an observational cross-sectional study. 50 patients with migraine (30 patients with aura and 20 patients without aura) and 50 healthy volunteers were included. Optical coherence tomography was performed with Optovue technology. The fast RNFL thickness (3.4) scan, MM5, and GCC acquisition protocols were used. Results: There was no statistically significant difference in retinal thickness in any of the quadrants between the control group and the migraine patients (p>0.05). The average RNFL thickness (110.50 vs 102.84 microns, p = 0.03) was significantly thinner in migrainers as compared to the control. The ANOVA did not reveal any significant difference between migrainers with aura, migrainers without aura, and the control group. The VAS (visual analogue scale) score of migraine patients was not statistically significantly correlated with any of the parameters, while the length of migraine history was negatively correlated with the average RNFL thickness (r = -0.32, p = 0.03). Conclusion: The average RNFL thickness in the migraine patients was found to be thinner than that in the control group. In addition, we found a negative weak correlation between length of migraine history and the average RNFL thickness, supporting the possible association between these pathologies. C1 [Yulek, Fatma; Ugurlu, Nagihan; CagIl, Nurullah] Yildirim Beyazit Univ, Ankara Ataturk Educ & Training Hosp, Fac Med, Dept Ophthalmol, Ankara, Turkey. [Dirik, Ebru Bilge; Eren, Yasemin] Yildirim Beyazit Univ, Ankara Ataturk Educ & Training Hosp, Fac Med, Dept Neurol, Ankara, Turkey. [Simavli, Huseyin] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Simavli, Huseyin] Izzet Baysal Bolu State Hosp, Dept Ophthalmol, Bolu, Turkey. [Simsek, Saban] Maltepe Univ, Fac Med, Dept Ophthalmol, Istanbul, Turkey. RP Simavli, H (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St,8th Floor, Boston, MA 02114 USA. EM huseyin_simavli@meei.harvard.edu RI Simavli, Huseyin/K-4404-2016; OI Simavli, Huseyin/0000-0003-1657-9099 NR 25 TC 5 Z9 5 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD MAR PY 2015 VL 30 IS 2 BP 124 EP 128 DI 10.3109/08820538.2013.833270 PG 5 WC Ophthalmology SC Ophthalmology GA CC6CF UT WOS:000350451500007 PM 24171810 ER PT J AU Fadlallah, A Jakobiec, FA Mendoza, PR Zalloua, PA Melki, SA AF Fadlallah, A. Jakobiec, F. A. Mendoza, P. R. Zalloua, P. A. Melki, S. A. TI Boston Type I Keratoprosthesis for Treatment of Gelatinous Drop-Like Corneal Dystrophy After Repeated Graft Failure SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Boston type I keratoprosthesis; genetic analysis; gelatinous drop-like corneal dystrophy ID SUBEPITHELIAL AMYLOIDOSIS; PATIENT AB Purpose: To describe the use of a Boston type I keratoprosthesis as a secondary penetrating procedure to treat gelatinous drop-like corneal dystrophy (GDLD), with presentation of pathologic findings, genetic analysis, and discussion of other surgical options. Methods: A 43-year-old woman with GDLD in both eyes, best corrected visual acuity (BCVA) of counting fingers in both eyes, and recurrent corneal opacification following two penetrating keratoplasties presented for visual rehabilitation. A Boston type I keratoprosthesis was implanted in her left eye after extracapsular clear lens extraction. Results: The surgery was uneventful and one month after surgery, best corrected vision improved to 20/30, which has been maintained for a period of more than nine months. At the 12-month visit, her vision was noted to be diminished to 20/200 due to a retroprosthetic membrane and improved to 20/25 two weeks after a Yag capsulotomy. Histopathologic examination of the corneal specimen disclosed predominantly subepithelial amyloid deposition. Genetic analysis is presented. Conclusions: GDLD is a rare disorder of primary corneal amyloidosis. Recurrence of this condition following surgery is very common. Boston type I keratoprosthesis as a secondary procedure can be successful in restoring vision in affected patients. C1 [Fadlallah, A.; Melki, S. A.] Beirut Eye Specialist Hosp, Beirut, Lebanon. [Fadlallah, A.] St Joseph Univ, Fac Med, Beirut, Lebanon. [Jakobiec, F. A.; Mendoza, P. R.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Jakobiec, F. A.; Mendoza, P. R.; Melki, S. A.] Harvard Univ, Sch Med, Boston, MA USA. [Zalloua, P. A.] Lebanese Amer Univ, Beirut, Lebanon. [Melki, S. A.] Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA 02114 USA. RP Melki, SA (reprint author), Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM samir_melki@meei.harvard.edu OI zalloua, pierre/0000-0002-8494-5081 NR 10 TC 2 Z9 2 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD MAR PY 2015 VL 30 IS 2 BP 150 EP 153 DI 10.3109/08820538.2013.833266 PG 4 WC Ophthalmology SC Ophthalmology GA CC6CF UT WOS:000350451500013 PM 24117413 ER PT J AU Holliday, EG Traylor, M Malik, R Bevan, S Falcone, G Hopewell, JC Cheng, YC Cotlarciuc, I Bis, JC Boerwinkle, E Boncoraglio, GB Clarke, R Cole, JW Fornage, M Furie, KL Ikram, MA Jannes, J Kittner, SJ Lincz, LF Maguire, JM Meschia, JF Mosley, TH Nalls, MA Oldmeadow, C Parati, EA Psaty, BM Rothwell, PM Seshadri, S Scott, RJ Sharma, P Sudlow, C Wiggins, KL Worrall, BB Rosand, J Mitchell, BD Dichgans, M Markus, HS Levi, C Attia, J Wray, NR AF Holliday, Elizabeth G. Traylor, Matthew Malik, Rainer Bevan, Steve Falcone, Guido Hopewell, Jemma C. Cheng, Yu-Ching Cotlarciuc, Ioana Bis, Joshua C. Boerwinkle, Eric Boncoraglio, Giorgio B. Clarke, Robert Cole, John W. Fornage, Myriam Furie, Karen L. Ikram, M. Arfan Jannes, Jim Kittner, Steven J. Lincz, Lisa F. Maguire, Jane M. Meschia, James F. Mosley, Thomas H. Nalls, Mike A. Oldmeadow, Christopher Parati, Eugenio A. Psaty, Bruce M. Rothwell, Peter M. Seshadri, Sudha Scott, Rodney J. Sharma, Pankaj Sudlow, Cathie Wiggins, Kerri L. Worrall, Bradford B. Rosand, Jonathan Mitchell, Braxton D. Dichgans, Martin Markus, Hugh S. Levi, Christopher Attia, John Wray, Naomi R. CA Australian Stroke Genetics Collabo Wellcome Trust Case Control Consor Int Stroke Genetics Consortium TI Genetic Overlap Between Diagnostic Subtypes of Ischemic Stroke SO STROKE LA English DT Article DE atherosclerosis; genetic epidemiology; lacunar stroke ID GENOME-WIDE ASSOCIATION; COMPLEX TRAITS; METAANALYSIS; VARIANTS; LINKAGE AB Background and Purpose-Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Methods-Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. Results-High genetic correlation was identified between LAA and SVD using linear mixed models (r(g)=0.96, SE=0.47, P=9x10(-4)) and profile scores (r(g)=0.72; 95% confidence interval, 0.52-0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1x10(-7)) for single nucleotide polymorphisms near the opioid receptor mu 1 (OPRM1) gene. Conclusions-Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes. C1 [Holliday, Elizabeth G.; Attia, John] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [Lincz, Lisa F.; Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, Callaghan, NSW 2308, Australia. [Maguire, Jane M.] Univ Newcastle, Sch Nursing & Midwifery, Callaghan, NSW 2308, Australia. [Holliday, Elizabeth G.; Oldmeadow, Christopher; Attia, John] Hunter Med Res Inst, Publ Hlth Res Program, Clin Res Design IT & Stat Support Unit, Newcastle, NSW, Australia. [Traylor, Matthew; Bevan, Steve; Markus, Hugh S.] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 1TN, England. [Malik, Rainer; Dichgans, Martin] Univ Munich, Klinikum Univ Mun Chen, Inst Stroke & Dementia Res, Munich, Germany. [Falcone, Guido; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Falcone, Guido; Rosand, Jonathan] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Hopewell, Jemma C.; Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford OX1 2JD, England. [Hopewell, Jemma C.; Clarke, Robert] Univ Oxford, Epidemiol Studies Unit, Oxford OX1 2JD, England. [Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford OX1 2JD, England. [Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Cole, John W.; Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Cotlarciuc, Ioana] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England. [Bis, Joshua C.; Psaty, Bruce M.; Wiggins, Kerri L.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. [Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Boncoraglio, Giorgio B.; Parati, Eugenio A.] IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy. [Cole, John W.; Kittner, Steven J.] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MD USA. [Furie, Karen L.] Rhode Isl Hosp, Dept Neurol, Providence, RI USA. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Jannes, Jim] Univ Adelaide, Sch Med, Adelaide, SA 5005, Australia. [Lincz, Lisa F.] Calvary Mater Newcastle Hosp, Hunter Haematol Res Grp, Newcastle, NSW, Australia. [Lincz, Lisa F.; Maguire, Jane M.; Scott, Rodney J.; Levi, Christopher] Hunter Med Res Inst, Newcastle, NSW, Australia. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med Geriatr, Jackson, MS 39216 USA. [Nalls, Mike A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Scott, Rodney J.] John Hunter Hosp, NSW Pathol, Newcastle, NSW, Australia. [Levi, Christopher] John Hunter Hosp, Dept Neurol, Newcastle, NSW, Australia. [Sharma, Pankaj] Royal Holloway Univ London ICR2UL & Ashford, Inst Cardiovasc Res, London, England. [Sharma, Pankaj] St Peters Hosp, Chertsey, England. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh EH8 9YL, Midlothian, Scotland. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. EM liz.holliday@newcastle.edu.au RI Boncoraglio, Giorgio/B-8647-2011; Wray, Naomi/C-8639-2015; OI Wray, Naomi/0000-0001-7421-3357; Seshadri, Sudha/0000-0001-6135-2622; Ikram, Mohammad Arfan/0000-0003-0372-8585; Traylor, Matthew/0000-0001-6624-8621; Bevan, Steve/0000-0003-0490-6830; Mitchell, Braxton/0000-0003-4920-4744 FU British Heart Foundation [FS/14/55/30806]; NHGRI NIH HHS [U01 HG005160]; NIA NIH HHS [R01 AG033193]; NIDCD NIH HHS [L30 DC006823]; NINDS NIH HHS [K08 NS045802, U01 NS069208]; The Dunhill Medical Trust [OSRP2/1006]; Wellcome Trust [095626] NR 30 TC 11 Z9 11 U1 0 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 MAR PY 2015 VL 46 IS 3 BP 615 EP + DI 10.1161/STROKEAHA.114.007930 PG 22 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CC3XP UT WOS:000350284900015 PM 25613305 ER PT J AU Sheth, KN Smith, EE Grau-Sepulveda, MV Kleindorfer, D Fonarow, GC Schwamm, LH AF Sheth, Kevin N. Smith, Eric E. Grau-Sepulveda, Maria V. Kleindorfer, Dawn Fonarow, Gregg C. Schwamm, Lee H. TI Drip and Ship Thrombolytic Therapy for Acute Ischemic Stroke Use, Temporal Trends, and Outcomes SO STROKE LA English DT Article DE emergency medicine; stroke; tissue-type plasminogen activator ID TISSUE-PLASMINOGEN ACTIVATOR; GUIDELINES-STROKE; MEDICARE BENEFICIARIES; 30-DAY MORTALITY; CARE; ASSOCIATION; IMPROVEMENT; ATTACK; REGISTRY; QUALITY AB Background and Purpose-Interhospital transfer after use of intravenous tissue-type plasminogen activator (tPA) in acute stroke (drip and ship) is increasingly frequent. Small studies have suggested that drip and ship tPA is safe and increases rates of tPA use; however, little is known about real-world practice patterns. We sought to evaluate temporal trends in drip and ship tPA use and to compare the patient and hospital characteristics with that of conventional (front door) thrombolysis. Methods-We analyzed data from 44 667 patients with ischemic stroke treated with intravenous tPA <= 3 hours of symptom onset in the Get With The Guidelines-Stroke program from April 2003 to October 2010 in 1440 hospitals. The main outcomes were the frequency of drip and ship tPA use over time, the characteristics of patients treated, and in-hospital outcomes, treatments, and complications. Results-Among 44 667 patients treated with tPA, the drip and ship method was a common method (n=10 475; 23.5%), the use of which increased in parallel with the traditional tPA method over time. Patients treated by the drip and ship method differed significantly from front-door patients, with lower National Institutes of Health Stroke Scale scores when recorded (n=35 467). Crude in-hospital mortality (10.9%) and symptomatic intracranial hemorrhage (5.7%) in patients treated by the drip and ship method were slightly higher compared with those in front-door patients, and these differences persisted after risk adjustment. Conclusions-Drip and ship tPA is common, used in 1 in 4 patients treated with tPA in the United States. Modest differences in mortality and symptomatic intracranial hemorrhage may be because of patient selection bias, post-tPA care differences, or unmeasured confounding. The drip and ship paradigm may facilitate widespread tPA use in patients with acute stroke. C1 [Sheth, Kevin N.] Yale Univ, Sch Med, Div Neurocrit Care & Emergency Neurol, Dept Neurol, New Haven, CT 06520 USA. [Sheth, Kevin N.] Yale Univ, Sch Med, Dept Neurosurg, Div Neurocrit Care & Emergency Neurol, New Haven, CT 06520 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Grau-Sepulveda, Maria V.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Kleindorfer, Dawn] Univ Cincinnati, Dept Neurol, Cincinnati, OH 45221 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Los Angeles, CA 90095 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. RP Sheth, KN (reprint author), Yale Univ, Sch Med, Div Neurocrit Care & Emergency Neurol, Dept Neurol, 15 York St,LCI 710A, New Haven, CT 06520 USA. EM kevin.sheth@yale.edu NR 21 TC 17 Z9 17 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAR PY 2015 VL 46 IS 3 BP 732 EP 739 DI 10.1161/STROKEAHA.114.007506 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CC3XP UT WOS:000350284900033 PM 25672784 ER PT J AU Wang, MP Wang, X Lam, TH Viswanath, K Chan, SS AF Wang, Man Ping Wang, Xin Lam, Tai Hing Viswanath, Kasisomayajula Chan, Sophia S. TI The tobacco endgame in Hong Kong: public support for a total ban on tobacco sales SO TOBACCO CONTROL LA English DT Article ID OPINION AB Background Tobacco endgame policies are increasingly advocated to end tobacco use. This study investigated public support for a total ban on tobacco sales, use and possession in Hong Kong. Methods A telephone survey was conducted among 1537 randomly selected residents in 2012 to assess their support for a total ban on tobacco sales, usage and possession. Information on sociodemographic characteristics, smoking, and second hand smoke exposure were collected. Logistic regression was used to investigate factors associated with support for a total ban. Results Most of the never smokers (75.3%), ex-smokers (63.9%), and nearly half of current smokers (48.9%) backed some form of a total ban on tobacco. A total ban on tobacco sales was the most popular option among the three groups, with over half (64.8%) of all respondents supporting a ban within 10 years. Current smoking and higher educational attainment were associated with less support for a total ban on tobacco sales. Among current smokers, having quit intentions and attempts to quit were associated with support for a total ban. Conclusions A total ban on tobacco sales was supported by most respondents. Ex-smokers and current smokers also voiced substantial support, although less than never smokers. A total ban on tobacco sales before 2022 should be the goal as it is supported by most of the respondents. Interim tobacco control measures, such as tax increases, expansion of smoking cessation services and plain packaging should be implemented to help current smokers quit and reduce smoking initiation before implementation of the ban. C1 [Wang, Man Ping; Wang, Xin; Lam, Tai Hing] Univ Hong Kong, Sch Publ Hlth, Pokfulam, Hong Kong, Peoples R China. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Ctr Community Based Res,Dana Farber Canc Inst, Boston, MA 02115 USA. [Chan, Sophia S.] Univ Hong Kong, Sch Nursing, Pokfulam, Hong Kong, Peoples R China. RP Lam, TH (reprint author), Univ Hong Kong, Sch Publ Hlth, 21 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China. EM hrmrlth@hku.hk FU Hong Kong Jockey Club Charities Trust FX This study was a part of the project 'FAMILY: A Jockey Club Initiative for a Harmonious Society,' which was funded by The Hong Kong Jockey Club Charities Trust. NR 28 TC 7 Z9 7 U1 2 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 EI 1468-3318 J9 TOB CONTROL JI Tob. Control PD MAR PY 2015 VL 24 IS 2 BP 162 EP 167 DI 10.1136/tobaccocontrol-2013-051092 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CC4QH UT WOS:000350337500018 PM 24046209 ER PT J AU Becker, A Pradel, L Kluth, L Schmid, M Eichelberg, C Ahyai, S Trinh, Q Seiler, D Dahlem, R Hansen, J Rink, M Zacharias, M Mehnert, A Bergelt, C Fisch, M Chun, FKH AF Becker, Andreas Pradel, Lea Kluth, Luis Schmid, Marianne Eichelberg, Christian Ahyai, Sascha Quoc Trinh Seiler, Daniel Dahlem, Roland Hansen, Jens Rink, Michael Zacharias, Mario Mehnert, Anja Bergelt, Corinna Fisch, Margit Chun, Felix K. H. TI Laparoscopic versus open partial nephrectomy for clinical T1 renal masses: no impact of surgical approach on perioperative complications and long-term postoperative quality of life SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Renal cell carcinoma; Renal mass; Quality of life; EORTC; Outcomes; Complication ID NEPHRON-SPARING SURGERY; CELL CARCINOMA; RADICAL NEPHRECTOMY; POPULATION; OUTCOMES; UTILITY; SYSTEM; SERIES; TUMORS AB Beyond oncological safety, consideration of 30-day complications according to Clavien-Dindo, as well as postoperative quality of life (QoL) after nephron-sparing surgery for clinical T1 renal masses, represents important factors for treatment decision counseling. The objective of this study was to compare the effect of laparoscopic versus open partial nephrectomy (LPN vs. OPN) on 30-day complications and long-term postoperative QoL for clinical T1 renal masses. Retrospective, longitudinal analysis of 293 patients treated with either LPN versus OPN for T1 renal masses. The investigated endpoints were 30-day Clavien-Dindo complications and health-related QoL (EORTC QLQ-C30). Respectively, logistic and linear regression models analyzed the effect of surgical partial nephrectomy approach on endpoints. Overall complication rates were similar in patients undergoing OPN or LPN (16.1 vs. 14.6 %, p = 0.8). Significantly less major complications (2.4 vs. 10.4 %, p = 0.025) occurred after LPN. Despite a shorter convalescence period for LPN patients (p = 0.035), in uni- and multivariable analyses, surgical approach was not associated with 30-day complications nor long-term differences in QoL (all p > 0.05). Despite a faster recovery time after LPN, our findings suggest that LPN and OPN are equivalent with regard to 30-day Clavien-Dindo complication rates and long-term QoL. C1 [Becker, Andreas; Pradel, Lea; Kluth, Luis; Schmid, Marianne; Eichelberg, Christian; Ahyai, Sascha; Dahlem, Roland; Hansen, Jens; Rink, Michael; Fisch, Margit; Chun, Felix K. H.] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Becker, Andreas] Univ Montreal Hlth Ctr, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Quoc Trinh] Harvard Univ, Sch Med, Dept Surg, Div Urol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Quoc Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Seiler, Daniel] Kantonsspital Aarau, Dept Urol, Aarau, Switzerland. [Zacharias, Mario] Vivantes Auguste Victoria Klinikum, Dept Urol, Berlin, Germany. [Mehnert, Anja; Bergelt, Corinna] Univ Med Ctr Hamburg Eppendorf, Dept & Outpatient Clin Med Psychol, Hamburg, Germany. RP Becker, A (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. EM a.becker@uke.de RI Mehnert, Anja/A-1177-2008 NR 26 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD MAR PY 2015 VL 33 IS 3 BP 421 EP 426 DI 10.1007/s00345-014-1318-1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA CC5AO UT WOS:000350369100018 PM 24879404 ER PT J AU Schranz, AJ Brady, KA Momplaisir, F Metlay, JP Stephens, A Yehia, BR AF Schranz, Asher J. Brady, Kathleen A. Momplaisir, Florence Metlay, Joshua P. Stephens, Alisa Yehia, Baligh R. TI Comparison of HIV Outcomes for Patients Linked at Hospital Versus Community-Based Clinics SO AIDS PATIENT CARE AND STDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; SUBSTANCE USE TREATMENT; SOCIETY-USA PANEL; HEALTH CENTERS; VIRAL SUPPRESSION; UNITED-STATES; INFECTED PATIENTS; MEDICAL-CARE; PHYSICIANS OFFICES AB Outpatient care for people living with HIV is delivered in diverse settings. Differences in setting may impact HIV outcomes. We evaluated HIV-infected adults in care at Ryan White-funded clinics in Philadelphia, PA, between 2008 and 2011 to determine how setting of care (hospital versus community-based) influenced HIV outcomes. Clinics were categorized as hospital-based if they were located onsite at a hospital. The composite outcome was completion of the final three steps of the HIV care continuum: (1) retention in care; (2) use of antiretroviral therapy (ART); and (3) viral suppression. Mixed-effects logistic regression, accounting for patient and clinic factors, examined the relationship between care setting and the outcome. In total, 12,637 patients, contributing 32,515 patient-years, received care at 25 clinics (12 hospital-based). Women, non-Hispanic blacks, those with private insurance, and individuals with higher household incomes more commonly attended hospital-based clinics (p<0.05). Of the 12,962 patient-years (40%) during which patients attended community-based clinics, 59% met the outcome. Similarly, 59% of the 19,553 patient-years (60%) in which patients attended hospital-based clinics met the outcome. Adjusting for patient and clinic factors, setting was not associated with the outcome (adjusted odds ratio=1.24, 95% CI=0.84-1.84). In summary, demographics differ among patients visiting hospital and community-based clinics. Completion of the final three steps of the HIV care continuum did not vary between hospital and community-based clinics, which may reflect advances in HIV therapy and the wide availability of HIV care resources. C1 [Schranz, Asher J.] NYU, Sch Med, Dept Med, New York, NY 10016 USA. [Brady, Kathleen A.; Yehia, Baligh R.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Stephens, Alisa; Yehia, Baligh R.] Univ Penn, Perelman Sch Med, Ctr Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Yehia, Baligh R.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Brady, Kathleen A.] Philadelphia Dept Publ Hlth, AIDS Activ Coordinating Off, Philadelphia, PA USA. [Momplaisir, Florence] Drexel Univ, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Schranz, AJ (reprint author), NYU, Sch Med, NBV 16 North 30,550 First Ave, New York, NY 10016 USA. EM asher.schranz@nyumc.org FU National Institutes of Health [K23-MH097647-01A] FX Funding: This study was supported by the National Institutes of Health (K23-MH097647-01A to BRY). NR 64 TC 0 Z9 0 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD MAR 1 PY 2015 VL 29 IS 3 BP 117 EP 125 DI 10.1089/apc.2014.0199 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CC3XE UT WOS:000350283700002 PM 25665013 ER PT J AU Movassaghian, M Sohani, AR McAfee, SL Perry, AM Dal Cin, P McLaughlin, C Fathi, AT AF Movassaghian, Maryam Sohani, Aliyah R. McAfee, Steven L. Perry, Ashley M. Dal Cin, Paola McLaughlin, Cynthia Fathi, Amir T. TI Chromosome 17p deletion in a case of T-cell acute lymphoblastic lymphoma SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material ID HEMATOLOGIC MALIGNANCIES C1 [Movassaghian, Maryam; McAfee, Steven L.; Perry, Ashley M.; Fathi, Amir T.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Sohani, Aliyah R.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Dal Cin, Paola; McLaughlin, Cynthia] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. RP Fathi, AT (reprint author), Massachusetts Gen Hosp, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA. EM afathi@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2015 VL 90 IS 3 BP 267 EP 268 DI 10.1002/ajh.23847 PG 2 WC Hematology SC Hematology GA CB8OJ UT WOS:000349889300024 PM 25195772 ER PT J AU Garg, M Lee, BE McGarry, K Mangray, S Castillo, JJ AF Garg, Megha Lee, Brian E. McGarry, Kelly Mangray, Shamlal Castillo, Jorge J. TI CD20-negative diffuse large B-cell lymphoma presenting with lactic acidosis SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID METABOLIC COMPLICATION; PROGNOSIS C1 [Garg, Megha; Lee, Brian E.; McGarry, Kelly] Brown Univ, Dept Med, Rhode Isl Hosp, Warren Alpert Med Sch, Providence, RI 02912 USA. [Mangray, Shamlal] Brown Univ, Dept Pathol, Rhode Isl Hosp, Warren Alpert Med Sch, Providence, RI 02912 USA. [Castillo, Jorge J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Garg, M (reprint author), 593 Eddy St JB 0100, Providence, RI 02903 USA. EM mgarg@lifespan.org OI Castillo, Jorge/0000-0001-9490-7532 NR 9 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 MAR PY 2015 VL 90 IS 3 BP E49 EP E50 DI 10.1002/ajh.23904 PG 2 WC Hematology SC Hematology GA CB8OJ UT WOS:000349889300004 PM 25417998 ER PT J AU Bieraugel, K Oehler, D NeSmith, M Chiovaro, J AF Bieraugel, Karen Oehler, Drew NeSmith, Meghan Chiovaro, Joseph TI Cat Got Your Spleen? Hepatosplenic Bartonella Infection SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID SCRATCH-DISEASE; HENSELAE INFECTION C1 [Bieraugel, Karen; Oehler, Drew; NeSmith, Meghan; Chiovaro, Joseph] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Chiovaro, Joseph] Portland VA Med Ctr, Dept Med, Portland, OR 97239 USA. RP Chiovaro, J (reprint author), Portland VA Med Ctr, Dept Med MED P3, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM jchiovaro@gmail.com NR 11 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD MAR PY 2015 VL 128 IS 3 BP 246 EP 249 DI 10.1016/j.amjmed.2014.11.003 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CC0DC UT WOS:000350004200021 PM 25460524 ER PT J AU Zakroysky, P Thai, WE Deano, RC Basnet, S Onandia, ZG Gandhi, S Tawakol, A Min, JK Truong, QA AF Zakroysky, Pearl Thai, Wai-ee Deano, Roderick C. Basnet, Sandeep Onandia, Zurine Galvan Gandhi, Sachin Tawakol, Ahmed Min, James K. Truong, Quynh A. TI Steroid Exposure, Acute Coronary Syndrome, and Inflammatory Bowel Disease: Insights into the Inflammatory Milieu SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Acute coronary syndrome; Crohn's disease; Inflammatory bowel disease; Ulcerative colitis; Steroids ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; HEART-DISEASE; RISK; GLUCOCORTICOIDS; EVENTS; PATHOGENESIS; COHORT AB BACKGROUND: Steroids are anti-inflammatory agents commonly used to treat inflammatory bowel disease. Inflammation plays a critical role in the pathophysiology of both inflammatory bowel disease and acute coronary syndrome. We examined the relationship between steroid use in patients with inflammatory bowel disease and acute coronary syndrome. METHODS: In 177 patients with inflammatory bowel disease (mean age 67 years, 75% male, 44% Crohn's disease, 56% ulcerative colitis), we performed a 1:2 case-control study matched for age, sex, and inflammatory bowel disease type, and compared 59 patients with inflammatory bowel disease with acute coronary syndrome to 118 patients with inflammatory bowel disease without acute coronary syndrome. Steroid use was defined as current or prior exposure. Acute coronary syndrome was defined as myocardial infarction or unstable angina, confirmed by cardiac biomarkers and coronary angiography. RESULTS: In patients with inflammatory bowel disease, 34% with acute coronary syndrome had exposure to steroids, vs 58% without acute coronary syndrome (P < .01). Steroid exposure reduced the adjusted odds of acute coronary syndrome by 82% (odds ratio [OR] 0.39; 95% confidence interval [CI], 0.20-0.74; adjusted OR 0.18; 95% CI, 0.06-0.51) in patients with inflammatory bowel disease, 77% in Crohn's disease (OR 0.36; 95% CI, 0.14-0.92; adjusted OR 0.23; 95% CI, 0.06-0.98), and 78% in ulcerative colitis (OR 0.41; 95% CI, 0.16-1.04; adjusted OR 0.22; 95% CI, 0.06-0.90). There was no association between other inflammatory bowel disease medications and acute coronary syndrome. CONCLUSIONS: In patients with inflammatory bowel disease, steroid use significantly reduces the odds of acute coronary syndrome. These findings provide further mechanistic insight into the inflammatory processes involved in inflammatory bowel disease and acute coronary syndrome. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zakroysky, Pearl] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Thai, Wai-ee; Basnet, Sandeep; Onandia, Zurine Galvan; Gandhi, Sachin; Tawakol, Ahmed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Cardiac MR PET CT Program, Boston, MA USA. [Thai, Wai-ee; Basnet, Sandeep; Onandia, Zurine Galvan; Gandhi, Sachin; Tawakol, Ahmed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Deano, Roderick C.] New York Presbyterian Hosp, Weill Cornell Med Coll, Div Cardiovasc Dis, New York, NY USA. [Min, James K.; Truong, Quynh A.] New York Presbyterian Hosp, Dalio Inst Cardiovasc Imaging, New York, NY USA. [Min, James K.; Truong, Quynh A.] Weill Cornell Med Coll, New York, NY USA. RP Truong, QA (reprint author), New York Presbyterian Hosp, Dalio Inst Cardiovasc Imaging, New York, NY 10021 USA. EM qat9001@med.cornell.edu FU National Institutes of Health [K23HL098370, L30HL093896] FX QAT received support from National Institutes of Health grants K23HL098370 and L30HL093896. NR 20 TC 3 Z9 4 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD MAR PY 2015 VL 128 IS 3 BP 303 EP 311 DI 10.1016/j.amjmed.2014.10.033 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CC0DC UT WOS:000350004200031 PM 25446295 ER PT J AU Bangalore, S Schwamm, L Smith, EE Singh, IM Liang, L Fonarow, GC Bhatt, DL AF Bangalore, Sripal Schwamm, Lee Smith, Eric E. Singh, Inder M. Liang, Li Fonarow, Gregg C. Bhatt, Deepak L. CA Get Guidelines Stroke Steering Com TI Quality of Care: A Long Way to Tipperary or a Long Way Down Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID SECONDARY PREVENTION; PERFORMANCE-MEASURES; ISCHEMIC-STROKE; MEDICATIONS; ASSOCIATION; DISCHARGE; ADHERENCE; OUTCOMES C1 [Bangalore, Sripal] NYU Med Ctr, New York, NY 10016 USA. [Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. [Singh, Inder M.] Mercy Heart & Vasc Inst, Sacramento, CA USA. [Liang, Li] Duke Clin Res Inst, Durham, NC USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bangalore, S (reprint author), NYU Med Ctr, New York, NY 10016 USA. RI Smith, Eric/C-5443-2012; OI Smith, Eric/0000-0003-3956-1668; Bangalore, Sripal/0000-0001-9485-0652 NR 7 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 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD MAR PY 2015 VL 128 IS 3 BP E15 EP E16 DI 10.1016/j.amjmed.2014.10.058 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CC0DC UT WOS:000350004200007 PM 25707888 ER PT J AU Kozin, ED Remenschneider, AK Shah, PV Reardon, E Lee, DJ AF Kozin, Elliott D. Remenschneider, Aaron K. Shah, Parth V. Reardon, Edward Lee, Daniel J. TI Endoscopic transcanal removal of symptomatic external auditory canal exostoses SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID SURGICAL-TREATMENT AB Exostoses are bony outgrowths of the external auditory canal (EAC) that can lead to cerumen entrapment, recurrent infections, and conductive hearing loss. When surgical removal is indicated, a drill or osteotome may be used via a post-auricular, endaural, or transcanal approach. Studies suggest that exostoses removed by transcanal osteotome result in decreased morbidity when compared to open, drilled approaches; however, inadvertent injury to the facial nerve or inner ear is a theoretical concern given the restrictive geometry of the EAC and challenges of visualizing the tip of the chisel through the microscope. The endoscope provides superior visualization of the external auditory canal and tympanic membrane compared to the microscope. We sought to demonstrate the efficacy and safety of endoscopic exostosis surgery with an osteotome. We find that the endoscope provides improved wide angled views without blind spots. There were no intraoperative complications. Endoscopic canaloplasty for exostoses may be readily applied. (C) 2015 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Kozin, ED (reprint author), 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 FU NIDCD NIH HHS [T32 DC000020] NR 5 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 EI 1532-818X J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD MAR-APR PY 2015 VL 36 IS 2 BP 283 EP 286 DI 10.1016/j.amjoto.2014.10.018 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA CB9FJ UT WOS:000349937100032 PM 25459316 ER PT J AU Gordon, JL Girdler, SS Meltzer-Brody, SE Stika, CS Thurston, RC Clark, CT Prairie, BA Moses-Kolko, E Joffe, H Wisner, KL AF Gordon, Jennifer L. Girdler, Susan S. Meltzer-Brody, Samantha E. Stika, Catherine S. Thurston, Rebecca C. Clark, Crystal T. Prairie, Beth A. Moses-Kolko, Eydie Joffe, Hadine Wisner, Katherine L. TI Ovarian Hormone Fluctuation, Neurosteroids, and HPA Axis Dysregulation in Perimenopausal Depression: A Novel Heuristic Model SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID CORTICOTROPIN-RELEASING HORMONE; MENOPAUSAL TRANSITION; MAJOR DEPRESSION; POSTMENOPAUSAL WOMEN; POSTPARTUM DEPRESSION; GABA(A) RECEPTORS; NATION SWAN; DEHYDROEPIANDROSTERONE LEVELS; CIRCULATING ALLOPREGNANOLONE; REPRODUCTIVE HORMONES AB Objective: In this conceptual review, the authors propose a novel mechanistic candidate in the etiology of depression with onset in the menopause transition ("perimenopausal depression") involving alterations in stress-responsive pathways, induced by ovarian hormone fluctuation. Method: The relevant literature in perimenopausal depression, including prevalence, predictors, and treatment with estrogen therapy, was reviewed. Subsequently, the growing evidence from animal models and clinical research in other reproductive mood disorders was synthesized to describe a heuristic model of perimenopausal depression development. Results: The rate of major depressive disorder and clinically meaningful elevations in depressive symptoms increases two- to threefold during the menopause transition. While the mechanisms by which ovarian hormone fluctuation might impact mood are poorly understood, growing evidence from basic and clinical research suggests that fluctuations in ovarian hormones and derived neurosteroids result in alterations in regulation of the HPA axis by gamma-aminobutyric acid (GABA). The authors' heuristic model suggests that for some women,, failure of the GABA(A) receptor to regulate overall GABA-ergic tone in the face of shifting levels of these neurosteroids may induce HPA axis dysfunction, thereby increasing sensitivity to stress and generating greater vulnerability to depression. Conclusions: The proposed model provides a basis for understanding the mechanisms by which the changing hormonal environment of the menopause transition may interact with the psychosocial environment of midlife to contribute to perimenopausal depression risk. Future research investigating this model may inform the development of novel pharmacological treatments for perimenopausal depression and related disorders, such as postpartum depression and premenstrual dysphoric disorder. C1 [Girdler, Susan S.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA. Northwestern Univ, Dept Obstet Gynecol, Chicago, IL 60611 USA. Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Allegheny Hlth Network, Dept Obstet & Gynecol, Pittsburgh, PA USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Girdler, SS (reprint author), Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA. EM susan_girdler@med.unc.edu FU NIMH [RO1 MH-087619]; Fonds de la Recherche du Quebec-Sante (FRQS); Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12 HD-055884]; North Carolina Translational and Clinical Sciences Institute; Canadian Institutes of Health Research (CIHR) Vanier Canada Graduate Scholarship; AstraZeneca; Foundation of Hope; Sage Pharmaceuticals; National Institute of Child Health and Human Development [HD-067185]; Cephalon/Teva FX Supported by NIMH grant RO1 MH-087619. Dr. Gordon is the recipient of a postdoctoral fellowship of the Fonds de la Recherche du Quebec-Sante (FRQS). Dr. Clark is supported in part by grant K12 HD-055884 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.; Dr. Gordon reports receiving a Pilot Project Grant from the North Carolina Translational and Clinical Sciences Institute; previously she was the recipient of a Canadian Institutes of Health Research (CIHR) Vanier Canada Graduate Scholarship. Dr Meltzer-Brody has received grant funding from AstraZeneca, the Foundation of Hope, and Sage Pharmaceuticals. Dr. Moses-Kolko has received support from grant HD-067185 from the National Institute of Child Health and Human Development Dr. Joffe receives research support from Cephalon/Teva, serves as consultant to Noven and Merck, and participates in an advisory board for Merck. Dr. Wisner serves as consultant to Quinn Emanuel Urquhart & Sullivan, L.L.P., which legally represents Pfizer Pharmaceutical Company; the Department of Psychiatry at Northwestern University receives contractual fees for Dr. Wisner's consultation to Quinn Emanuel Urquhart & Sullivan. The other authors report no financial relationships with commercial interests. NR 85 TC 17 Z9 18 U1 2 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2015 VL 172 IS 3 BP 227 EP 236 DI 10.1176/appi.ajp.2014.14070918 PG 10 WC Psychiatry SC Psychiatry GA CC0DW UT WOS:000350007000008 PM 25585035 ER PT J AU Chen, T Yuan, J Duncanson, S Hibert, ML Kodish, BC Mylavaganam, G Maker, M Li, H Sremac, M Santosuosso, M Forbes, B Kashiwagi, S Cao, J Lei, J Thomas, M Hartono, C Sachs, D Markmann, J Sambanis, A Poznansky, MC AF Chen, T. Yuan, J. Duncanson, S. Hibert, M. L. Kodish, B. C. Mylavaganam, G. Maker, M. Li, H. Sremac, M. Santosuosso, M. Forbes, B. Kashiwagi, S. Cao, J. Lei, J. Thomas, M. Hartono, C. Sachs, D. Markmann, J. Sambanis, A. Poznansky, M. C. TI Alginate Encapsulant Incorporating CXCL12 Supports Long-Term Allo- and Xenoislet Transplantation Without Systemic Immune Suppression SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE basic (laboratory) research; science; kidney transplantation; nephrology; xenotransplantation; animal models; kidney biology ID REGULATORY T-CELLS; MESENCHYMAL STEM-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NOD MICE; ISLET TRANSPLANTATION; DIABETES-MELLITUS; PANCREATIC-ISLETS; ACTIVE MOVEMENT; BONE-MARROW; SURVIVAL AB Islet transplantation represents a potentially curative approach for individuals with Type I Diabetes. The requirement for systemic immune suppression to control immune-mediated rejection of transplanted islets and the limited human islet supply represent significant roadblocks to progress for this approach. Islet microencapsulation in alginate offers limited protection in the absence of systemic immunosuppression, but does not support long-term islet survival. The chemokine, CXCL12, can repel effector T cells while recruiting immune-suppressive regulatory T cells (Tregs) to an anatomic site while providing a prosurvival signal for beta-cells. We proposed that coating or encapsulating donor islets with CXCL12 would induce local immune-isolation and protect and support the function of an allo- or xenograft without systemic immune suppression. This study investigated the effect of alginate microcapsules incorporating CXCL12 on islet function. Islet transplantation was performed in murine models of insulin-dependent diabetes. Coating of islets with CXCL12 or microencapsulation of islets with alginate incorporating the chemokine, resulted in long-term allo- and xenoislet survival and function, as well as a selective increase in intragraft Tregs. These data support the use of CXCL12 as a coating or a component of an alginate encapsulant to induce sustained local immune-isolation for allo- or xenoislet transplantation without systemic immunosuppression. An alginate microencapsulant incorporating CXCL12 acts as a T cell chemorepellent and an islet prosurvival factor that supports long-term allo- and xenoislet transplantation without systemic immune suppression in mouse models of diabetes. C1 [Chen, T.; Yuan, J.; Hibert, M. L.; Kodish, B. C.; Mylavaganam, G.; Maker, M.; Li, H.; Sremac, M.; Santosuosso, M.; Forbes, B.; Kashiwagi, S.; Cao, J.; Poznansky, M. C.] Massachusetts Gen Hosp, Vaccine & Immunotherapy Ctr, Charlestown, MA 02129 USA. [Duncanson, S.; Sambanis, A.] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. [Lei, J.] Dept Transplantat Surg, Boston, MA USA. [Thomas, M.] Massachusetts Gen Hosp, Dept Endocrinol, Boston, MA 02114 USA. [Hartono, C.] Cornell Weill Med Sch, New York, NY USA. [Sachs, D.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. [Markmann, J.] Georgia Inst Technol, Sch Chem & Biomol Engn, Atlanta, GA 30332 USA. RP Poznansky, MC (reprint author), Massachusetts Gen Hosp, Vaccine & Immunotherapy Ctr, Charlestown, MA 02129 USA. EM mpoznansky@partners.org FU Juvenile Diabetes Research Foundation; Friends of VIC FX Zurab Machaidze, Zachary Thompson, Marguerite Bradley and Ben Campbell provided technical support for the islet encapsulation protocol and its execution. This work was supported by the Juvenile Diabetes Research Foundation and The Friends of VIC. NR 52 TC 10 Z9 11 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2015 VL 15 IS 3 BP 618 EP 627 DI 10.1111/ajt.13049 PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA CB9UD UT WOS:000349977700010 PM 25693473 ER PT J AU Shafi, MM Vernet, M Klooster, D Chu, CJ Boric, K Barnard, ME Romatoski, K Westover, MB Christodoulou, JA Gabrieli, JDE Whitfield-Gabrieli, S Pascual-Leone, A Chang, BS AF Shafi, Mouhsin M. Vernet, Marine Klooster, Debby Chu, Catherine J. Boric, Katica Barnard, Mollie E. Romatoski, Kelsey Westover, M. Brandon Christodoulou, Joanna A. Gabrieli, John D. E. Whitfield-Gabrieli, Susan Pascual-Leone, Alvaro Chang, Bernard S. TI Physiological Consequences of Abnormal Connectivity in a Developmental Epilepsy SO ANNALS OF NEUROLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; PERIVENTRICULAR NODULAR HETEROTOPIA; TEMPORAL-LOBE EPILEPSY; FUNCTIONAL CONNECTIVITY; CORTICAL EXCITABILITY; HUMAN BRAIN; TMS-EEG; FOCAL EPILEPSY; RESPONSES; TARGETS AB ObjectiveMany forms of epilepsy are associated with aberrant neuronal connections, but the relationship between such pathological connectivity and the underlying physiological predisposition to seizures is unclear. We sought to characterize the cortical excitability profile of a developmental form of epilepsy known to have structural and functional connectivity abnormalities. MethodsWe employed transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) recording in 8 patients with epilepsy from periventricular nodular heterotopia and matched healthy controls. We used connectivity imaging findings to guide TMS targeting and compared the evoked responses to single-pulse stimulation from different cortical regions. ResultsHeterotopia patients with active epilepsy demonstrated a relatively augmented late cortical response that was greater than that of matched controls. This abnormality was specific to cortical regions with connectivity to subcortical heterotopic gray matter. Topographic mapping of the late response differences showed distributed cortical networks that were not limited to the stimulation site, and source analysis in 1 subject revealed that the generator of abnormal TMS-evoked activity overlapped with the spike and seizure onset zone. InterpretationOur findings indicate that patients with epilepsy from gray matter heterotopia have altered cortical physiology consistent with hyperexcitability, and that this abnormality is specifically linked to the presence of aberrant connectivity. These results support the idea that TMS-EEG could be a useful biomarker in epilepsy in gray matter heterotopia, expand our understanding of circuit mechanisms of epileptogenesis, and have potential implications for therapeutic neuromodulation in similar epileptic conditions associated with deep lesions. Ann Neurol 2015;77:487-503 C1 [Shafi, Mouhsin M.; Vernet, Marine; Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. [Shafi, Mouhsin M.; Vernet, Marine; Chu, Catherine J.; Boric, Katica; Romatoski, Kelsey; Westover, M. Brandon; Pascual-Leone, Alvaro; Chang, Bernard S.] Harvard Univ, Sch Med, Boston, MA USA. [Shafi, Mouhsin M.; Romatoski, Kelsey; Chang, Bernard S.] Beth Israel Deaconess Med Ctr, Dept Neurol, Comprehens Epilepsy Ctr, Boston, MA 02215 USA. [Klooster, Debby] Acad Ctr Epileptol, Kempenhaeghe, Heeze, Netherlands. [Chu, Catherine J.; Boric, Katica; Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Barnard, Mollie E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Christodoulou, Joanna A.] MGH Inst Hlth Profess, Dept Commun Sci & Disorders, Boston, MA USA. [Gabrieli, John D. E.; Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Shafi, MM (reprint author), Beth Israel Deaconess Med Ctr, West Baker 5,330 Brookline Ave, Boston, MA 02215 USA. EM mshafi@bidmc.harvard.edu FU KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst/Harvard Clinical and Translational Science Center (NIH National Center for Research Resources [NCRR]); KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences [NCATS]) [KL2 TR001100]; Fyssen Foundation; NIH/NINDS [5K12NS066225]; American Brain Foundation; Sidney R. Baer Jr Foundation; NIH [NICHD R01 HD069776, NINDS R01 NS073601, NIMH R21 MH099196, NINDS R21 NS082870, NINDS R21 NS085491, NICHD R21 HD07616]; Harvard Catalyst/Harvard Clinical and Translational Science Center (NIH NCRR); Harvard Catalyst/Harvard Clinical and Translational Science Center (NCATS) [UL1 RR025758]; NIH National Institute of Neurological Disorders and Stroke [R01 NS073601] FX M.M.S. was supported by a KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst/Harvard Clinical and Translational Science Center (NIH National Center for Research Resources [NCRR] and National Center for Advancing Translational Sciences [NCATS], KL2 TR001100). M.V. was supported by the Fyssen Foundation. C.J.C. was supported by the NIH/NINDS (5K12NS066225). M.B.W. was supported the American Brain Foundation. A. P.-L. was supported by grants from the Sidney R. Baer Jr Foundation, NIH (NICHD R01 HD069776, NINDS R01 NS073601, NIMH R21 MH099196, NINDS R21 NS082870, NINDS R21 NS085491, NICHD R21 HD07616), and Harvard Catalyst/Harvard Clinical and Translational Science Center (NIH NCRR and the NCATS, UL1 RR025758). B.S.C. was supported by the NIH National Institute of Neurological Disorders and Stroke (R01 NS073601, with subcontract to J.D.E.G.). NR 55 TC 9 Z9 9 U1 1 U2 5 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 MAR PY 2015 VL 77 IS 3 BP 487 EP 503 DI 10.1002/ana.24343 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CC6EC UT WOS:000350456800013 PM 25858773 ER PT J AU Cavusoglu, E Marmur, JD Hegde, S Yanamadala, S Batuman, OA Chopra, V Ay, G Eng, C AF Cavusoglu, Erdal Marmur, Jonathan D. Hegde, Sudhanva Yanamadala, Sunitha Batuman, Olcay A. Chopra, Vineet Ay, Gonca Eng, Calvin TI Relation of baseline plasma MMP-1 levels to long-term all-cause mortality in patients with known or suspected coronary artery disease referred for coronary angiography SO ATHEROSCLEROSIS LA English DT Article DE Matrix metalloproteinase 1; Biomarkers; Acute coronary syndrome; Prognosis; Mortality ID INDEPENDENT PREDICTOR; HEART-FAILURE; METALLOPROTEINASE EXPRESSION; MATRIX METALLOPROTEINASES; MYOCARDIAL-INFARCTION; REGIONS; PLAQUES; RISK; PAR1 AB Objectives: To investigate the long-term prognostic significance of baseline plasma MMP-1 levels in a group of well-characterized male patients with known or suspected coronary artery disease, including those presenting with acute coronary syndrome. Background: MMP-1 is an interstitial collagenase that is considered the primary enzyme responsible for collagen degradation. In addition, MMP-1 can lead to platelet activation through the PAR1 pathway that is independent of thrombin. Methods: Baseline plasma MMP-1 levels were measured in 364 male patients who were referred for coronary angiography and followed prospectively for five years for the development of all-cause mortality. Results: After adjustment for a variety of baseline clinical, angiographic and laboratory parameters, baseline plasma MMP-1 levels (analyzed as a continuous variable) were an independent predictor of all-cause mortality at 5 years (HR, 1.49; 95% CI, 1.23-1.80; P < 0.0001). Furthermore, in 3 additional multivariate models that included a wide variety of contemporary biomarkers with established prognostic efficacy (i.e., ST2, GDF-15, Cystatin C, hs-CRP, Myeloperoxidase, NT-proBNP, TIMP-1, Adiponectin, RDW, hemoglobin, and Erythropoietin), MMP-1 remained an independent predictor of all-cause mortality at 5 years. Similar results were obtained when the analyses were restricted to the subpopulation of patients presenting with acute coronary syndrome. Conclusions: Elevated levels of MMP-1 are associated with an increased risk of long-term all-cause mortality in patients with known or suspected coronary disease that is independent of a variety of clinical, angiographic, and laboratory variables, including a whole host of contemporary biomarkers with established prognostic efficacy representing multiple different pathophysiologic processes. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Cavusoglu, Erdal; Chopra, Vineet; Eng, Calvin] Bronx Vet Affairs Med Ctr, Dept Med, Div Cardiol, Bronx, NY USA. [Cavusoglu, Erdal; Marmur, Jonathan D.; Hegde, Sudhanva; Yanamadala, Sunitha] Suny Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. [Batuman, Olcay A.] Suny Downstate Med Ctr, Dept Med, Div Hematol, Brooklyn, NY 11203 USA. [Ay, Gonca] Mersin Univ, Dept Biol Sci, Mersin, Turkey. RP Cavusoglu, E (reprint author), Suny Downstate Med Ctr, 450 Clarkson Ave,Box 1199, Brooklyn, NY 11203 USA. EM ECavusoglu@aol.com FU American Heart Association [10GRNT3700003]; NIH-NHLBI [5R21HL098661-02] FX This study was sponsored, in part, by grants related to biomarkers from the American Heart Association (Grant-in-Aid 10GRNT3700003) and the NIH-NHLBI (5R21HL098661-02). NR 23 TC 1 Z9 3 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAR PY 2015 VL 239 IS 1 BP 268 EP 275 DI 10.1016/j.atherosclerosis.2015.01.003 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CB6RH UT WOS:000349753800039 PM 25635325 ER PT J AU Hershenberg, R Goldfried, MR AF Hershenberg, Rachel Goldfried, Marvin R. TI Implications of RDoC for the Research and Practice of Psychotherapy SO BEHAVIOR THERAPY LA English DT Article DE evidence-based practice; empirically supported treatments; clinical trials; psychotherapy research; research domain criteria ID RESEARCH DOMAIN CRITERIA; CONTROLLED CLINICAL-TRIALS; PRACTICE RESEARCH NETWORK; BEHAVIORAL ACTIVATION; PSYCHIATRIC-DIAGNOSIS; COGNITIVE THERAPY; PSYCHOPATHOLOGY; DEPRESSION; MODEL; EXPERIENCES AB The field of psychotherapy is at an important juncture. Recent changes in the field include (a) the skeptical reception of the fifth edition of the Diagnostic and Statistical Manual and (b) NIMH's prioritization of an alternative classification system to guide translational and intervention research. Moreover, (c) the field continues to be held accountable to governmental agencies and third-party payers to demonstrate its empirical basis. Thus, psychological research as it relates to the practice of psychotherapy is at a crossroads. In this article, we provide a brief overview of several generations of psychotherapy outcome research, including the consequences that followed in the 1980s as psychotherapy research moved toward randomized controlled trials for clinical disorders. We delineate the inherent strengths and limitations of this movement and address how the NIMH has recently responded with the Research Domain Criteria (RDoC). We then address philosophical and practical implications of the emphasis on a neuroscientific conceptualization of psychological problems. Finally, we discuss opportunities for a next generation of convergent science that incorporates, rather than replaces, psychosocial variables across stages of translational research and treatment development. C1 [Hershenberg, Rachel] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Hershenberg, Rachel] Univ Penn, Philadelphia, PA 19104 USA. [Goldfried, Marvin R.] SUNY Stony Brook, Stony Brook, NY USA. RP Hershenberg, R (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave,Mailstop 116, Philadelphia, PA 19104 USA. EM rhersh@mail.med.upenn.edu NR 67 TC 8 Z9 8 U1 2 U2 11 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD MAR PY 2015 VL 46 IS 2 BP 156 EP 165 PG 10 WC Psychology, Clinical SC Psychology GA CC0FX UT WOS:000350012300002 PM 25645165 ER PT J AU Thompson-Hollands, J Abramovitch, A Tompson, MC Barlow, DH AF Thompson-Hollands, Johanna Abramovitch, Amitai Tompson, Martha C. Barlow, David H. TI A Randomized Clinical Trial of a Brief Family Intervention to Reduce Accommodation in Obsessive-Compulsive Disorder: A Preliminary Study SO BEHAVIOR THERAPY LA English DT Article DE accommodation; family; obsessive-compulsive disorder ID QUALITY-OF-LIFE; DSM-IV ANXIETY; EMOTIONAL DISORDERS; TRANSDIAGNOSTIC TREATMENT; PSYCHOMETRIC PROPERTIES; BEHAVIORAL TREATMENT; UNIFIED PROTOCOL; MOOD DISORDERS; INVENTORY; CLASSIFICATION AB Accommodation consists of changes in family members' behavior to prevent or reduce patients' obsessive compulsive disorder (OCD) rituals or distress. High levels of family accommodation are associated with more severe symptoms and functional impairment in patients, and may also interfere with exposure-based treatment. The purpose of this study was to develop and test an intervention to reduce accommodation in the family members of adult OCD patients. Patients (N = 18, mean age = 35.44,33% male, 94% Caucasian) received a course of standard individual exposure and ritual prevention (ERP) for OCD. Family members (N = 18, mean age = 41.72, 56% male, 94% Caucasian) were randomized to either receive or not receive the adjunctive intervention, consisting of two sessions of psychoeducation and skills training in reducing accommodation. Results revealed that the intervention successfully reduced scores on the clinician-rated Family Accommodation Scale (Week 8: d = 1.05). Patients whose family members received the intervention showed greater reductions in Yale-Brown Obsessive Compulsive Scale scores across treatment than patients whose family members had not (Week 8: d = 1.27), and hierarchical regression analyses revealed that change in family accommodation from baseline accounted for a significant amount of variance in later OCD symptoms (beta=.45, p =.02). Results from this preliminary study suggest that adjunctive intervention produces more rapid treatment response compared with traditional ERP alone. Accommodation is a potentially important target for improving treatment in OCD and other diagnostic groups where accommodation is likely to occur. C1 [Thompson-Hollands, Johanna; Tompson, Martha C.; Barlow, David H.] Boston Univ, Boston, MA 02139 USA. [Abramovitch, Amitai] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Thompson-Hollands, J (reprint author), Boston Univ, 648 Beacon St,Floor 6, Boston, MA 02139 USA. EM hollands@bu.edu FU National Institutes of Mental Health [F31MH092996]; Association for Behavioral and Cognitive Therapies FX This research was supported by a fellowship from the National Institutes of Mental Health to the first author under award number F31MH092996. The content reported here is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Mental Health. Financial support for the present study was also provided from the Association for Behavioral and Cognitive Therapies. NR 50 TC 7 Z9 8 U1 2 U2 9 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD MAR PY 2015 VL 46 IS 2 BP 218 EP 229 PG 12 WC Psychology, Clinical SC Psychology GA CC0FX UT WOS:000350012300007 PM 25645170 ER PT J AU Jagasia, MH Greinix, HT Arora, M Williams, KM Wolff, D Cowen, EW Palmer, J Weisdorf, D Treister, NS Cheng, GS Kerr, H Stratton, P Duarte, RF McDonald, GB Inamoto, Y Vigorito, A Arai, S Datiles, MB Jacobsohn, D Heller, T Kitko, CL Mitchell, SA Martin, PJ Shulman, H Wu, RS Cutler, CS Vogelsang, GB Lee, SJ Pavletic, SZ Flowers, MED AF Jagasia, Madan H. Greinix, Hildegard T. Arora, Mukta Williams, Kirsten M. Wolff, Daniel Cowen, Edward W. Palmer, Jeanne Weisdorf, Daniel Treister, Nathaniel S. Cheng, Guang-Shing Kerr, Holly Stratton, Pamela Duarte, Rafael F. McDonald, George B. Inamoto, Yoshihiro Vigorito, Afonso Arai, Sally Datiles, Manuel B. Jacobsohn, David Heller, Theo Kitko, Carrie L. Mitchell, Sandra A. Martin, Paul J. Shulman, Howard Wu, Roy S. Cutler, Corey S. Vogelsang, Georgia B. Lee, Stephanie J. Pavletic, Steven Z. Flowers, Mary E. D. TI National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic graft-versus-host disease; National Institutes of Health; Diagnosis; Staging ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; CHRONIC GVHD CONSORTIUM; RISK-FACTORS; NONRELAPSE MORTALITY; SURVIVAL; SEVERITY; OUTCOMES; SCORE; ORGAN AB The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic graft-versus-host disease (GVHD). The 2014 NIH consensus maintains the framework of the prior consensus with further refinement based on new evidence. Revisions have been made to address areas of controversy or confusion, such as the overlap chronic GVHD subcategory and the distinction between active disease and past tissue damage. Diagnostic criteria for involvement of mouth, eyes, genitalia, and lungs have been revised. Categories of chronic GVHD should be defined in ways that indicate prognosis, guide treatment, and define eligibility for clinical trials. Revisions have been made to focus attention on the causes of organ-specific abnormalities. Attribution of organ-specific abnormalities to chronic GVHD has been addressed. This paradigm shift provides greater specificity and more accurately measures the global burden of disease attributed to GVHD, and it will facilitate biomarker association studies. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Dept Hematol & Oncol, Nashville, TN 37235 USA. [Greinix, Hildegard T.] Med Univ Vienna, Dept Internal Med, Vienna, Austria. [Arora, Mukta; Weisdorf, Daniel] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Williams, Kirsten M.; Cowen, Edward W.; Pavletic, Steven Z.] Ctr Canc Res, Natl Canc Inst, NIH, Bethesda, MD USA. [Williams, Kirsten M.; Jacobsohn, David] Childrens Natl Hlth Syst, Dept Blood & Marrow Transplantat, Washington, DC USA. [Weisdorf, Daniel] Univ Regensburg, Dept Internal Med, D-93053 Regensburg, Germany. [Palmer, Jeanne] Mayo Clin Arizona, Dept Hematol Oncol Blood & Marrow Transplant, Phoenix, AZ USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Dept Surg, Div Oral Med & Dent, Boston, MA 02115 USA. [Cheng, Guang-Shing; McDonald, George B.; Martin, Paul J.; Shulman, Howard; Lee, Stephanie J.; Flowers, Mary E. D.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Kerr, Holly] BC Canc Agcy, Dept Hematol, Vancouver, BC, Canada. [Stratton, Pamela] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. [Duarte, Rafael F.] Inst Catala Oncol, Dept Hematol, Barcelona, Spain. [Inamoto, Yoshihiro] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan. [Vigorito, Afonso] Hemoctr Unicamp, Hematol & Hemotherapy Ctr, Campinas, SP, Brazil. [Arai, Sally] Stanford Univ, Med Ctr, Dept Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Datiles, Manuel B.] NIH, Natl Eye Inst, Eye Clin, Bethesda, MD 20892 USA. [Heller, Theo] NIH, Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, Bethesda, MD 20892 USA. [Kitko, Carrie L.] Univ Michigan, Ctr Comprehens Canc, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Mitchell, Sandra A.] NIH, Dept Appl Res Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Wu, Roy S.] NIH, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Cutler, Corey S.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA USA. [Vogelsang, Georgia B.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. RP Flowers, MED (reprint author), Fred Hutchinson Canc Res Ctr, D5-290 POB 19024, Seattle, WA 98109 USA. EM mflowers@fredhutch.org OI Datiles, Manuel III B./0000-0003-4660-1664 FU NIH's 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; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; National Cancer Institute [CA18029, CA118953]; National Institutes of Health FX This project was supported by the NIH's 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; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources. This work was also supported in part by grants CA18029 and CA118953 from the National Cancer Institute and the National Institutes of Health. 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 ORDR/NCATS and NCI), German-Austrian-Swiss chronic 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 de Matos Silva and Vaneuza Funke) and Deutsche Jose Carreras Leukamie-Stiftung. The authors would like to thank Dr. Joseph Antin (Dana Farber Cancer Center, Boston, MA) and Dr. Gerard Socie (University Paris VII & AP-HP, Hospital Saint Louis, Paris, France) for their critical review of the manuscript. The authors also thank Marcie Hall for careful review of the manuscript. 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. For their expert contributions to this 2014 NIH Consensus Diagnosis and Staging Working Group document special acknowledgements go to Drs. Mark Schubert, Fred Hutchinson Cancer Research Center in Seattle, WA, Tina Dietrich-Ntoukas, University of Regensburg, Germany, Janine Clayton, National Eye Institute, NIH, Bethesda, MD, Melissa A. Merideth, National Human Genome Research Institute, NIH, Bethesda, MD, Tajana Klepac Pulanic, Community Health Center East, Zagreb, Croatia, and Robert Knobler, University of Vienna, Austria. NR 51 TC 87 Z9 90 U1 6 U2 12 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 MAR PY 2015 VL 21 IS 3 BP 389 EP 401 DI 10.1016/j.bbmt.2014.12.001 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CC0EV UT WOS:000350009500004 PM 25529383 ER PT J AU Villa, A Aboalela, A Luskin, KA Cutler, CS Sonis, ST Bin Woo, S Peterson, DE Treister, NS AF Villa, Alessandro Aboalela, Ali Luskin, Katharine A. Cutler, Corey S. Sonis, Stephen T. Bin Woo, Sook Peterson, Douglas E. Treister, Nathaniel S. TI Mammalian Target of Rapamycin Inhibitor-Associated Stomatitis in Hematopoietic Stem Cell Transplantation Patients Receiving Sirolimus Prophylaxis for Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Graft-versus-host-disease; Sirolimus; Ulcers; Management ID GVHD PROPHYLAXIS; RENAL-ALLOGRAFTS; ACUTE REJECTION; RECIPIENTS; MANAGEMENT; MTOR; IMMUNOSUPPRESSION; CYCLOSPORINE; EFFICACY; THERAPY AB The mammalian target of rapamycin (mTOR) inhibitor sirolimus is effective in reducing incidence of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Agents that inhibit the mTOR pathway are known to be associated with significant and potentially dose-limiting toxictries, including stomatitis. The objective of this study was to report the clinical features and management outcomes of sirolimus-associated oral ulcers in the context of post-HSCT prophylaxis of GVHD. Seventeen patients, from a study cohort of 967, who were treated with sirolimus as prophylaxis for GVHD after allogeneic HSCT at the Dana-Farber/Brigham and Women's Cancer Center developed oral ulcers and were referred to the oral medicine clinic for evaluation and treatment over a period of 6 years. Clinical characteristics (appearance, anatomic site, size) and therapeutic outcomes (time to complete resolution) were documented. Median time to onset of oral ulceration was 55 days after allogeneic HSCT (range, 6 to 387 days); 92.9% of ulcers were located on nonkeratinized mucosa, with the ventrolateral tongue the most common site of involvement. Thirteen patients were treated with topical corticosteroid therapy; 12 of these patients also required intralesional corticosteroid injections. Clinical improvement (resolution of the lesions and improvement of symptoms) was noted in all cases, with no reported adverse events. Median time to complete resolution after onset of therapy was 14 days (range, 2 to 70 days). Patients receiving sirolimus for GVHD prophylaxis may develop painful oral ulcerations, which can be effectively managed with topical steroid treatment. Further prospective studies are needed to better elucidate the incidence of this complication, identify risk factors, and evaluate the effectiveness of interventions. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Villa, Alessandro; Aboalela, Ali; Sonis, Stephen T.; Bin Woo, Sook; Treister, Nathaniel S.] Harvard Univ, Sch Dent Med, Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Villa, Alessandro; Aboalela, Ali; Sonis, Stephen T.; Bin Woo, Sook; Treister, Nathaniel S.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Luskin, Katharine A.; Peterson, Douglas E.] Univ Connecticut, Ctr Hlth, Sch Dent Med, Farmington, CT USA. [Cutler, Corey S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Peterson, Douglas E.] Univ Connecticut, Ctr Hlth, Sch Dent Med, Dept Oral Hlth & Diagnost Sci, Farmington, CT USA. [Peterson, Douglas E.] Univ Connecticut, Ctr Hlth, Neag Comprehens Canc Ctr, Farmington, CT USA. RP Villa, A (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,Suite BC-3-028, Boston, MA 02120 USA. EM avilla@partners.org FU University of Connecticut Department of Oral Health & Diagnostic Sciences [4-04078]; University of Connecticut School of Dental Medicine Alumni Research Fellowship FX This work was partially sponsored by the University of Connecticut Department of Oral Health & Diagnostic Sciences Account 4-04078 and the University of Connecticut School of Dental Medicine Alumni Research Fellowship. NR 24 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2015 VL 21 IS 3 BP 503 EP 508 DI 10.1016/j.bbmt.2014.11.680 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CC0EV UT WOS:000350009500018 PM 25482865 ER PT J AU Spring, L Li, S Soiffer, RJ Antin, JH Alyea, EP Glotzbecker, B AF Spring, Laura Li, Shuli Soiffer, Robert J. Antin, Joseph H. Alyea, Edwin P., III Glotzbecker, Brett TI Risk Factors for Readmission after Allogeneic Hematopoietic Stem Cell Transplantation and Impact on Overall Survival SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Readmission; Allogeneic hematopoietic stem cell transplantation; Survival ID HEART-FAILURE; 30-DAY READMISSION; MEDICARE BENEFICIARIES; RATES; PHYSICIAN; CARE AB Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) are presumed to be at high risk for hospital readmission. The objective of this study was to identify the incidence and associated risk factors for readmissions in allogeneic HSCT patients and to evaluate the effect of readmissions on overall survival. In this retrospective review, we included 1141 HSCT patients (503 patients receiving a myeloablative [MAC] HSCT and 638 a reduced-intensity conditioning [RIC] HSCT). We measured rates of readmission at 30 days after discharge from HSCT and by day +100 after HSCT. Reasons for readmission, risk factors for readmission, and effect on overall survival were assessed. In the MAC group, 130 of 459 (28.3%) patients were readmitted within 30 days of discharge and 195 of 456 (42.8%) patients by day 100. In the RIC group, 105 of 600 (17.5%) patients were readmitted within 30 days of discharge and 185 of 595 (31.1%) patients by day 100. There were significantly more readmissions in the MAC group at both the 30-day (P < .001) and day +100 time points (P < .001). The most frequent reason for readmission was infection (28.2% in MAC group, 27.3% in RIC group). The occurrence of infection during the index admission was the only risk factor significant in both groups at both time points in the multivariable regression analysis. Readmission was significantly associated with decreased overall survival in both groups and at both time points. MAC patients are readmitted significantly more than RIC patients. Infection is the most common cause of readmission after HSCT and the occurrence of infection during the index transplantation admission is a significant risk factor for readmission. Readmission within 30 days of discharge and by day +100 after transplantation was a significant risk factor for a lower 5-year overall survival rate in both groups. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Spring, Laura; Li, Shuli; Soiffer, Robert J.; Antin, Joseph H.; Alyea, Edwin P., III; Glotzbecker, Brett] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Glotzbecker, B (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, 450 Brookline Ave,Dana 104B, Boston, MA 02215 USA. EM brett_glotzbecker@dfci.harvard.edu NR 23 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2015 VL 21 IS 3 BP 509 EP 516 DI 10.1016/j.bbmt.2014.11.682 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CC0EV UT WOS:000350009500019 PM 25482866 ER PT J AU Copelan, EA Avalos, BR Ahn, KW Zhu, XC Gale, RP Grunwald, MR Hamadani, M Hamilton, BK Hale, GA Marks, DI Waller, EK Savani, BN Costa, LJ Ramanathan, M Cahn, JY Khoury, HJ Weisdorf, DJ Inamoto, Y Kamble, RT Schouten, HC Wirk, B Litzow, MR Aljurf, MD van Besien, KW Ustun, C Bolwell, BJ Bredeson, CN Fasan, O Ghosh, N Horowitz, MM Arora, M Szer, J Loren, AW Alyea, EP Cortes, J Maziarz, RT Kalaycio, ME Saber, W AF Copelan, Edward A. Avalos, Belinda R. Ahn, Kwang Woo Zhu, Xiaochun Gale, Robert Peter Grunwald, Michael R. Hamadani, Mehdi Hamilton, Betty K. Hale, Gregory A. Marks, David I. Waller, Edmund K. Savani, Bipin N. Costa, Luciano J. Ramanathan, Muthalagu Cahn, Jean-Yves Khoury, H. Jean Weisdorf, Daniel J. Inamoto, Yoshihiro Kamble, Rammurti T. Schouten, Harry C. Wirk, Baldeep Litzow, Mark R. Aljurf, Mahmoud D. van Besien, Koen W. Ustun, Celalettin Bolwell, Brian J. Bredeson, Christopher N. Fasan, Omotayo Ghosh, Nilanjan Horowitz, Mary M. Arora, Mukta Szer, Jeffrey Loren, Alison W. Alyea, Edwin P. Cortes, Jorge Maziarz, Richard T. Kalaycio, Matt E. Saber, Wael TI Comparison of Outcomes of Allogeneic Transplantation for Chronic Myeloid Leukemia with Cyclophosphamide in Combination with Intravenous Busulfan, Oral Busulfan, or Total Body Irradiation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic myeloid leukemia; Busulfan; Total body irradiation ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; CHRONIC GRANULOCYTIC-LEUKEMIA; PREPARATIVE REGIMEN; CHRONIC-PHASE; VENOOCCLUSIVE DISEASE; MYELOGENOUS LEUKEMIA; RANDOMIZED-TRIAL; 1ST REMISSION; SURVIVAL AB Cyclophosphamide (Cy) in combination with busulfan (Bu) or total body irradiation (TBI) is the most commonly used myeloablative conditioning regimen in patients with chronic myeloid leukemia (CML). We used data from the Center for International Bone Marrow Transplantation Research to compare outcomes in adults who underwent hematopoietic cell transplantation for CIVIL in first chronic phase after myeloablative conditioning with Cy in combination with TBI, oral Bu, or intravenous (i.v.) Bu. Four hundred thirty-eight adults received human leukocyte antigen (HLA)-matched sibling grafts and 235 received well-matched grafts from unrelated donors (URD) from 2000 through 2006. Important differences existed between the groups in distribution of donor relation, exposure to tyrosine kinase inhibitors, and year of transplantation. In multivariate analysis, relapse occurred less frequently among patients receiving i.v. Bu compared with TB! (relative risk ERR], .36; P = .022) or oral Bu (RR, .39; P = .028), but nonrelapse mortality and survival were similar. A significant interaction was detected between donor relation and the main effect in leukemia-free survival (LFS). Among recipients of HLA-identical sibling grafts, but not URD grafts, LFS was better in patients receiving i.v. Bu (RR, .53; P = .025) or oral Bu (RR, .64; P = .017) compared with TBI. In CML in first chronic phase, Cy in combination with i.v. Bu was associated with less relapse than TBI or oral Bu. LFS was better after i.v. or oral Bu compared with TBI. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Copelan, Edward A.; Avalos, Belinda R.; Grunwald, Michael R.; Fasan, Omotayo; Ghosh, Nilanjan] Carolinas Hlthcare Syst, Levirte Canc Inst, Charlotte, NC USA. [Ahn, Kwang Woo] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Ahn, Kwang Woo; Zhu, Xiaochun; Hamadani, Mehdi; Horowitz, Mary M.; Saber, Wael] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Hematol Res Ctr, Dept Med, Div Expt Med, London, England. [Hamilton, Betty K.; Bolwell, Brian J.] Cleveland Clin, Dept Hematol & Oncol, Cleveland, OH 44106 USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, Dept Hematol Oncol, St Petersburg, FL 33701 USA. [Marks, David I.] Univ Hosp Bristol NHS Trust, Bristol, Avon, England. [Waller, Edmund K.; Khoury, H. Jean] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN 37235 USA. [Costa, Luciano J.] Med Univ S Carolina, Dept Med, Div Hematol Oncol, Charleston, SC 29425 USA. [Ramanathan, Muthalagu] UMass Mem Med Ctr, Div Hematol Oncol, Worcester, MA USA. [Cahn, Jean-Yves] Univ Hosp, Dept Hematol, Grenoble, France. [Weisdorf, Daniel J.; Ustun, Celalettin; Arora, Mukta] Univ Minnesota, Med Ctr, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Inamoto, Yoshihiro] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Div Hematol & Oncol, Houston, TX 77030 USA. [Schouten, Harry C.] Acad Ziekenhuis, Div Hematol, Maastricht, Netherlands. [Wirk, Baldeep] SUNY Stony Brook, Med Ctr, Dept Internal Med, Stony Brook, NY 11794 USA. [Litzow, Mark R.] Mayo Clin, Dept Hematol, Rochester, MN USA. [Aljurf, Mahmoud D.] King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia. [van Besien, Koen W.] Weill Cornell Med Coll, Dept Med Oncol, New York, NY USA. [Bredeson, Christopher N.] Ottawa Hosp, Blood Marrow Transplant Program, Ottawa, ON, Canada. [Bredeson, Christopher N.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. [Szer, Jeffrey] Royal Melbourne Hosp, Dept Clin Haematol & Bone Marrow Transplantat, Parkville, Vic 3050, Australia. [Loren, Alison W.] Univ Penn, Perelman Sch Med, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Alyea, Edwin P.] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. [Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Div Canc Med, Houston, TX 77030 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. RP Copelan, EA (reprint author), Levine Canc Inst, 1021 Morehead Med Dr,Suite 5300, Charlotte, NC 28204 USA. EM Heather.T.Johnson@carolinashealthcare.org FU Public Health Service Grant from National Cancer Institute [U24-CA76518]; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases; NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen; Angioblast; Ariad; Be The Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; Therakos FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases; a grant/cooperative agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc.; Amgen; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be The Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; Therakos; and Well Point The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the US Government. NR 33 TC 4 Z9 4 U1 2 U2 9 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 MAR PY 2015 VL 21 IS 3 BP 552 EP 558 DI 10.1016/j.bbmt.2014.12.010 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CC0EV UT WOS:000350009500025 PM 25528388 ER PT J AU Hoss, AG Labadorf, A Latourelle, JC Kartha, VK Hadzi, TC Gusella, JF MacDonald, ME Chen, JF Akbarian, S Weng, ZP Vonsattel, JP Myers, RH AF Hoss, Andrew G. Labadorf, Adam Latourelle, Jeanne C. Kartha, Vinay K. Hadzi, Tiffany C. Gusella, James F. MacDonald, Marcy E. Chen, Jiang-Fan Akbarian, Schahram Weng, Zhiping Vonsattel, Jean Paul Myers, Richard H. TI miR-10b-5p expression in Huntington's disease brain relates to age of onset and the extent of striatal involvement SO BMC MEDICAL GENOMICS LA English DT Article DE Huntington's disease; Human; Prefrontal cortex; Striatum; miRNA-sequencing; microRNA; miRNA; RNA biology; Age at onset; Neuropathological involvement ID RNA-SEQ DATA; GENE-EXPRESSION; NEUROTROPHIC FACTOR; NONCODING RNAS; MICRORNA; DYSREGULATION; MODELS; MIRNA; IDENTIFICATION; DEGENERATION AB Background: MicroRNAs (miRNAs) are small non-coding RNAs that recognize sites of complementarity of target messenger RNAs, resulting in transcriptional regulation and translational repression of target genes. In Huntington's disease (HD), a neurodegenerative disease caused by a trinucleotide repeat expansion, miRNA dyregulation has been reported, which may impact gene expression and modify the progression and severity of HD. Methods: We performed next-generation miRNA sequence analysis in prefrontal cortex (Brodmann Area 9) from 26 HD, 2 HD gene positive, and 36 control brains. Neuropathological information was available for all HD brains, including age at disease onset, CAG-repeat size, Vonsattel grade, and Hadzi-Vonsattel striatal and cortical scores, a continuous measure of the extent of neurodegeneration. Linear models were performed to examine the relationship of miRNA expression to these clinical features, and messenger RNA targets of associated miRNAs were tested for gene ontology term enrichment. Results: We identified 75 miRNAs differentially expressed in HD brain (FDR q-value <0.05). Among the HD brains, nine miRNAs were significantly associated with Vonsattel grade of neuropathological involvement and three of these, miR-10b-5p, miR-10b-3p, and miR-302a-3p, significantly related to the Hadzi-Vonsattel striatal score (a continuous measure of striatal involvement) after adjustment for CAG length. Five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-10b-3p, and miR-106a-5p) were identified as having a significant relationship to CAG length-adjusted age of onset including miR-10b-5p, the mostly strongly over-expressed miRNA in HD cases. Although prefrontal cortex was the source of tissue profiled in these studies, the relationship of miR-10b-5p expression to striatal involvement in the disease was independent of cortical involvement. Correlation of miRNAs to the clinical features clustered by direction of effect and the gene targets of the observed miRNAs showed association to processes relating to nervous system development and transcriptional regulation. Conclusions: These results demonstrate that miRNA expression in cortical BA9 provides insight into striatal involvement and support a role for these miRNAs, particularly miR-10b-5p, in HD pathogenicity. The miRNAs identified in our studies of postmortem brain tissue may be detectable in peripheral fluids and thus warrant consideration as accessible biomarkers for disease stage, rate of progression, and other important clinical characteristics of HD. C1 [Hoss, Andrew G.; Labadorf, Adam; Latourelle, Jeanne C.; Hadzi, Tiffany C.; Chen, Jiang-Fan; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Hoss, Andrew G.] Boston Univ, Sch Med, Grad Program Genet & Genom, Boston, MA 02215 USA. [Labadorf, Adam; Kartha, Vinay K.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Gusella, James F.; MacDonald, Marcy E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Akbarian, Schahram] Mt Sinai Sch Med, Friedman Brain Inst, Dept Psychiat, New York, NY USA. [Weng, Zhiping] Univ Massachusetts, Sch Med, Program Bioinformat & Integrat Biol, Worcester, MA 01605 USA. [Weng, Zhiping] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA. [Vonsattel, Jean Paul] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY USA. [Vonsattel, Jean Paul] New York Presbyterian Hosp, New York, NY USA. [Myers, Richard H.] Boston Univ, Sch Med, Genome Sci Inst, Boston, MA 02215 USA. RP Myers, RH (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. EM rmyers@bu.edu OI Labadorf, Adam/0000-0002-0753-8992 FU Jerry McDonald HD Research Fund; US National Institutes of Health (Epigenetic Markers in Huntington's disease Brain) [R01NS073947]; US National Institutes of Health (Dopaminergic Epigenomes From Human Brain) [R21NS076958]; US National Institutes of Health (Delineating the Huntington's Disease Mechanism by Manipulating the Mouse HD) [R01NS032765]; 2013 Firefly Frontiers Grant FX Jerry McDonald HD Research Fund; US National Institutes of Health (R01NS073947 Epigenetic Markers in Huntington's disease Brain, R21NS076958 Dopaminergic Epigenomes From Human Brain, R01NS032765 Delineating the Huntington's Disease Mechanism by Manipulating the Mouse HD); 2013 Firefly Frontiers Grant. NR 59 TC 9 Z9 9 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD MAR 1 PY 2015 VL 8 AR 10 DI 10.1186/s12920-015-0083-3 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA CC3QA UT WOS:000350262800001 PM 25889241 ER PT J AU Ding, XB Zhou, XH Wang, QH AF Ding, Xiaobo Zhou, Xiao-Hua Wang, Qihua TI A partially linear single-index transformation model and its nonparametric estimation SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE Basis function; Cross validation; linear inequality restriction; local linear regression; minimum average variance estimation ID DIMENSION REDUCTION; SEMIPARAMETRIC ESTIMATION; REGRESSION-MODEL AB In this paper, we consider the nonparametric estimation of the partially linear single-index transformation model, where the transformation function, single-index function and error distribution are all completely unknown. We first use the minimum average variance estimation method to estimate the regression coefficients, and then propose a new incorporated local linear regression estimator for the derivative function of the single-index function. Accordingly by integration we can obtain the estimator of the single-index function. Finally we propose a constrained least square estimator for the transformation function, where basis function approximation is employed and cross validation method is proposed to select suitable sets of basis functions. Asymptotical properties of the estimators are established. Simulation studies show that our proposed estimators work well. A real-world data analysis of total health care charges was used to illustrate the proposed procedure. The Canadian Journal of Statistics 43: 97-117; 2015 (c) 2015 Statistical Society of Canada Resume Les auteurs traitent de l'estimation non parametrique du modele de transformation partiellement lineaire a un indice dans le cas oU la transformation, la fonction d'indice et la distribution de l'erreur sont toutes completement inconnues. Ils estiment d'abord les coefficients de regression par la methode de la variance moyenne minimale, puis ils proposent un nouvel estimateur local de regression lineaire pour la derivee de la fonction d'indice, menant a l'estimation de cette fonction par integration. Finalement, ils proposent un estimateur aux moindres carres avec contraintes pour la fonction de transformation dont une approximation est effectuee a l'aide de fonctions de base, elles-memes selectionnees par une procedure de validation croisee. Les auteurs etablissent les proprietes asymptotiques de leurs estimateurs et montrent a l'aide de simulations que ceux-ci donnent de bons resultats. Ils illustrent egalement leur methode en analysant un jeu de donnees reelles portant sur les couts des soins de sante. La revue canadienne de statistique 43: 97-117; 2015 (c) 2015 Societe statistique du Canada C1 [Ding, Xiaobo; Wang, Qihua] Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China. [Ding, Xiaobo; Zhou, Xiao-Hua] Vet Affairs Puget Sound Hlth Care Syst, HSR& Ctr Excellence, Seattle, WA 98108 USA. [Ding, Xiaobo; Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Wang, Qihua] Shenzhen Univ, Inst Stat Sci, Shenzhen, Guangdong, Peoples R China. RP Zhou, XH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, HSR& Ctr Excellence, Seattle, WA 98108 USA. EM azhou@u.washington.edu FU U.S. Department of Veterans Affairs, Veterans Affairs Health Administration, Health Science Research and Development grant [RCS 05-196]; National Natural Science Foundation of China; Key Laboratory of Random Complex Structures and Data Science, Chinese Academy of Sciences; National Science Fund for Creative Research Groups in China; Natural Science Foundation of Shenzhen University FX The authors thank the review editor and the two anonymous reviewers for their useful comments and suggestions, which led to a great improvement of the paper. Xiao-Hua (Andrew) Zhou, Ph.D., is presently a Core Investigator and Biostatistics Unit Director at the Seattle/Denver Center of Innovation for Veteran-Centered and Value-Driven Care, Department of Veterans Affairs Medical Center, Seattle, WA. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. Dr. Zhou's work was supported in part by U.S. Department of Veterans Affairs, Veterans Affairs Health Administration, Health Science Research and Development grant (RCS 05-196). Ding's research was supported in part by a research grant from the National Natural Science Foundation of China. Ding and Wang's research was also supported by the Key Laboratory of Random Complex Structures and Data Science, Chinese Academy of Sciences. Wang's research was supported by the National Natural Science Foundation of China, the National Science Fund for Creative Research Groups in China, and Natural Science Foundation of Shenzhen University. NR 27 TC 1 Z9 1 U1 4 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0319-5724 EI 1708-945X J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD MAR PY 2015 VL 43 IS 1 BP 97 EP 117 DI 10.1002/cjs.11239 PG 21 WC Statistics & Probability SC Mathematics GA CC1YF UT WOS:000350140600006 ER PT J AU Gray, PJ Lin, CC Sineshaw, H Paly, JJ Jemal, A Efstathiou, JA AF Gray, Phillip J. Lin, Chun Chieh Sineshaw, Helmneh Paly, Jonathan J. Jemal, Ahmedin Efstathiou, Jason A. TI Management Trends in Stage I Testicular Seminoma: Impact of Race, Insurance Status, and Treatment Facility SO CANCER LA English DT Article DE chemotherapy; practice patterns; radiotherapy; seminoma; testicular cancer ID CANCER DATA-BASE; INVASIVE BLADDER-CANCER; LONG-TERM SURVIVORS; GERM-CELL CANCER; RANDOMIZED-TRIAL; UNITED-STATES; ADJUVANT TREATMENT; SURVEILLANCE; RISK; RADIOTHERAPY AB BACKGROUNDThe management of stage I testicular seminoma is evolving rapidly. This study examined modern trends in the management of stage I testicular seminoma and the effects of sociodemographic factors on therapy choice. METHODSData from the National Cancer Data Base on 34,067 patients with stage I testicular seminoma who were treated between 1998 and 2011 were analyzed. Multivariate logistic regression models were used to assess factors associated with adjuvant management strategies. RESULTSFor patients with stage IA/B testicular seminoma, rates of observation after orchiectomy increased from 23.7% to 54.0%, the receipt of adjuvant chemotherapy increased from 1.5% to 16.0%, and the receipt of radiotherapy decreased from 70.8% to 28.8%. A similar pattern was seen in stage IS testicular seminoma, although these patients were more likely to receive adjuvant radiotherapy/chemotherapy (60.7% vs 44.8% for stage IA/B in 2011, P<.001). For patients with stage IA/B testicular seminoma, observation after orchiectomy was more common in racial minorities (odds ratio [OR] for blacks vs whites, 1.31, P<.001; OR for Hispanics vs whites, 1.39, P<.001) and in the uninsured (OR for uninsured vs privately insured, 1.33, P<.001) and less common at community centers (OR for community centers vs National Cancer Institute-designated cancer centers, 0.80, P=.044). In those with stage IA/B testicular seminoma who received adjuvant radiotherapy/chemotherapy, the receipt of chemotherapy was more common at academic centers and for patients with nonprivate insurance. CONCLUSIONSPostorchiectomy observation in stage I testicular seminoma has increased significantly in recent years, as has the receipt of chemotherapy, whereas the receipt of radiotherapy has declined, particularly at academic centers. Race, insurance status, and facility type are strongly associated with the choice of adjuvant management. Cancer 2015;121:681-687. (c) 2014 American Cancer Society. In an analysis of 34,067 patients with stage I testicular seminoma, the rate of observation after orchiectomy increases from 23.7% in 1998 to 54.0% in 2011. Racial minorities, the uninsured, and those treated at academic centers are more likely to receive observation. C1 [Gray, Phillip J.; Paly, Jonathan J.; Efstathiou, Jason A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Lin, Chun Chieh; Sineshaw, Helmneh; Jemal, Ahmedin] Amer Canc Soc, Surveillance & Hlth Serv Res Program, Atlanta, GA 30329 USA. RP Gray, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM pjgray@partners.org FU American Cancer Society FX This study was funded by American Cancer Society intramural research funding. NR 38 TC 9 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAR 1 PY 2015 VL 121 IS 5 BP 681 EP 687 DI 10.1002/cncr.29094 PG 7 WC Oncology SC Oncology GA CB9WY UT WOS:000349986100007 PM 25345675 ER PT J AU Freedman, RA Kouri, EM West, DW Keating, NL AF Freedman, Rachel A. Kouri, Elena M. West, Dee W. Keating, Nancy L. TI Racial/Ethnic Disparities in Knowledge About One's Breast Cancer Characteristics SO CANCER LA English DT Article DE breast cancer; knowledge; disparities; health literacy; education ID TREATMENT DECISION-MAKING; FUNCTIONAL HEALTH LITERACY; INCREASING MAMMOGRAPHY; RANDOMIZED-TRIAL; CHRONIC DISEASE; OLDER-PEOPLE; WOMEN; CARE; COMMUNICATION; DETERMINANTS AB BACKGROUNDUnderstanding tumor characteristics is likely important, but little is known about breast cancer patients' knowledge of their own disease. The authors assessed women's knowledge about their tumor characteristics, whether racial/ethnic disparities in knowledge exist, and whether education and health literacy influence associations. METHODSA population-based cohort of women in Northern California with stage 0 through III breast cancers diagnosed from 2010 to 2011 (participation rate 68.5%) was surveyed. Among 500 respondents (222 non-Hispanic white women, 142 non-Hispanic black women, and 136 Hispanic women), racial/ethnic differences in knowledge about tumor characteristics (estrogen receptor [ER] status, human epidermal growth factor receptor 2 [HER2] status, stage, grade) and correctness of tumor information (with California Cancer Registry data for confirmation) were examined. Multivariate logistic regression was used to assess the probability of: 1) knowing tumor stage, receptor status, and grade; and 2) correctly answering questions about tumor information by race/ethnicity. The impact of education and health literacy on findings was examined in sequential models. RESULTSOverall, 32% to 82% of women reported knowing each of the 4 tumor characteristics of interest, and 20% to 58% correctly reported these characteristics. After adjustment, black and Hispanic women were less likely than white women to know and have correct responses for stage, ER status, and HER2 status (all P<.05). Education and health literacy were significantly associated with knowing and having correct information about some characteristics, but these variables did not eliminate most of the racial/ethnic differences observed. CONCLUSIONSPatient's knowledge about their own breast cancer was generally poor, particularly for minority women. Further study of how this knowledge may impact receipt of care and outcomes is warranted. Cancer 2015;121:724-732. (c) 2014 American Cancer Society. Women's knowledge about their breast cancer characteristics was generally poor for all patients, and minority, less educated, and older women were the least likely to know and correctly report characteristics. C1 [Freedman, Rachel A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Kouri, Elena M.; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [West, Dee W.] Inst Publ Hlth, Canc Registry Greater Calif, Sacramento, CA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org FU Komen for the Cure Foundation; National Cancer Institute's Surveillance, Epidemiology and End Results Program [HHSN261201000140C, HHSN261201000035C, HHSN261201000034C]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U58DP003862-01] FX This work was supported by Komen for the Cure Foundation. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the state-wide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement U58DP003862-01 awarded to the California Department of Public Health. NR 42 TC 8 Z9 8 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAR 1 PY 2015 VL 121 IS 5 BP 724 EP 732 DI 10.1002/cncr.28977 PG 9 WC Oncology SC Oncology GA CB9WY UT WOS:000349986100012 PM 25624186 ER PT J AU Wang, DS Jani, AB Sesay, M Tai, CG Lee, DK Echt, KV Goodman, MG Kilbridge, KE Master, VA AF Wang, Daniel S. Jani, Ashesh B. Sesay, Musu Tai, Caroline G. Lee, Daniel K. Echt, Katharina V. Goodman, Michael G. Kilbridge, Kerry E. Master, Viraj A. TI Video-Based Educational Tool Improves Patient Comprehension of Common Prostate Health Terminology SO CANCER LA English DT Article DE health literacy; multimedia; patient education; prostate cancer; shared decision making ID RADICAL PROSTATECTOMY; CANCER; KNOWLEDGE; COMPUTER; SOCIETY; BENEFIT; TERMS; PRINT; MEN AB BACKGROUNDHealth care providers often counsel prostate cancer patients about treatment options with medical terminology. However, studies have demonstrated a severe lack of comprehension of these terms, particularly in underserved populations. It was hypothesized that a video-based educational tool would significantly improve the understanding of key terms related to prostate health in a predominantly lower literacy population. METHODSA software application was developed by various experts, including urologists and human-computer interaction specialists, to serve as a video-based educational tool emphasizing narrated animations to promote understanding of terms related to urinary, bowel, and sexual function. This application was viewed by patients recruited from 2 low-income safety net clinics, where a previously developed survey was administered to assess pre- and postintervention levels of comprehension. RESULTSFifty-six patients with a mean literacy level of 7th to 8th grade completed the study. Patients achieved statistically significant improvements in comprehension for the majority of the terms after the video intervention, with notable improvements including the terms incontinence (from 14% to 50%), bowels (from 14% to 46%), and impotence (from 58% to 84%). Patients demonstrated significant gains in their understanding of the function of the prostate (from 11% to 30%) and in their ability to locate the prostate on anatomic drawings (from 50% to 82%). CONCLUSIONSThis video-based educational tool is an effective method for overcoming the severe lack of comprehension of prostate health terminology among patients. The improvements achieved have the potential to enhance patient participation in shared and informed decision making and to support combined visual-audio multimedia as a promising tool for prostate cancer education. Cancer 2015;121:733-740. (c) 2014 American Cancer Society. Recent studies have revealed a disheartening lack of comprehension of medical terms often used in counseling patients about treatment options. To address this vital component of shared decision making, a video-based educational tool has been developed, and it results in significant gains in patient comprehension of such terminology. C1 [Wang, Daniel S.] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Jani, Ashesh B.] Emory Univ, Sch Med, Emory Winship Canc Inst, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Sesay, Musu; Tai, Caroline G.; Lee, Daniel K.; Master, Viraj A.] Emory Univ, Sch Med, Emory Winship Canc Inst, Dept Urol, Atlanta, GA 30322 USA. [Echt, Katharina V.] Emory Univ, Sch Med, Emory Winship Canc Inst, Dept Med, Atlanta, GA 30322 USA. [Echt, Katharina V.] Atlanta Vet Affairs Med Ctr, Birmingham Atlanta Vet Affairs Geriatr Res Educ &, Atlanta, GA USA. [Echt, Katharina V.] Atlanta Vet Affairs Med Ctr, Atlanta Vet Affairs Rehabil Res & Dev Ctr Excelle, Atlanta, GA USA. [Goodman, Michael G.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Kilbridge, Kerry E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kilbridge, Kerry E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. RP Master, VA (reprint author), Emory Univ, Sch Med, Emory Winship Canc Inst, Dept Urol, 1365 Clifton Rd Northeast,Bldg B,Suite 1400, Atlanta, GA 30322 USA. EM vmaster@emory.edu FU Winship Cancer Institute of Emory University FX This work was supported by a Multi-Investigator Research Seed Grant from the Winship Cancer Institute of Emory University (coprincipal investigators: Viraj A. Master, Ashesh B. Jani, and Michael Goodman). NR 31 TC 8 Z9 8 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAR 1 PY 2015 VL 121 IS 5 BP 733 EP 740 DI 10.1002/cncr.29101 PG 8 WC Oncology SC Oncology GA CB9WY UT WOS:000349986100013 PM 25393416 ER PT J AU Somayaji, D Cloyes, KG AF Somayaji, Darryl Cloyes, Kristin Gates TI Cancer Fear and Fatalism How African American Participants Construct the Role of Research Subject in Relation to Clinical Cancer Research SO CANCER NURSING LA English DT Article DE African American; Cancer; Fatalism; Fear; Identity; Race; Research subject ID CRITICAL RACE THEORY; AGE-BASED DISPARITIES; HEALTH-CARE-SYSTEM; UNDERREPRESENTED POPULATIONS; EDUCATIONAL INTERVENTION; OLDER-ADULTS; TRIALS; RECRUITMENT; BREAST; RACE/ETHNICITY AB Background: Lack of African American participation in cancer clinical trials has been identified as a critical problem. Historical interactions related to race, identity, and power may contribute to continued inequity in healthcare and research participation. Objective: The aim of this study was to explore the perceptions of African Americans regarding cancer and research and how these perceptions shape their beliefs about participating as cancer research subjects. Methods: Three African American focus groups were conducted including people who had never participated in cancer research, those who had, and those who were asked but refused (n = 16). Discussion focused on their perceptions of cancer research and actual or potential participation as research subjects. Data were coded using both structured and inductive coding methods. Results: Fear and fatalism emerged in relation to research, race, power, and identity and were related to larger historical and social issues rather than only individual thoughts or feelings. Participants described fears of the unknown, death, mistrust, conspiracy, and discrimination together with positive/negative tensions between self, family, and community responsibilities. Conclusion: Complex identities linked perceptions of cancer and cancer research with broader historical and cultural issues. Fear, fatalism, and current and historical relationships influence how people perceive themselves as research subjects and may influence their decisions to participate in cancer research. Implication for Practice: Acknowledging how complex factors including race and racism contribute to health disparities may give nurses and other healthcare providers a better appreciation of how historical, social, and cultural dynamics at individual, community, and organizational levels influence access to and participation in cancer research. C1 [Somayaji, Darryl] Univ Massachusetts, Phyllis F Cantor Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cloyes, Kristin Gates] Univ Utah, Sch Nursing, Salt Lake City, UT USA. RP Somayaji, D (reprint author), Univ Massachusetts, Phyllis F Cantor Ctr, Dana Farber Canc Inst, 450 Brookline Ave,L522, Boston, MA 02115 USA. EM darryl_somayaji@dfci.harvard.edu FU American Cancer Society [113737-DSCN-07-131-01-SCN, 117201-DSCNR-07-137-03-SCN] FX American Cancer Society Doctoral Degree Scholarship in Cancer Nursing Award ID: 113737-DSCN-07-131-01-SCN; 117201-DSCNR-07-137-03-SCN. NR 45 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 0162-220X EI 1538-9804 J9 CANCER NURS JI Cancer Nurs. PD MAR-APR PY 2015 VL 38 IS 2 BP 133 EP 144 DI 10.1097/NCC.0000000000000144 PG 12 WC Oncology; Nursing SC Oncology; Nursing GA CB8UV UT WOS:000349907900014 PM 24945262 ER PT J AU Elvington, M Schepp-Berglind, J Tomlinson, S AF Elvington, M. Schepp-Berglind, J. Tomlinson, S. TI Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of dextran sulphate sodium-induced colitis SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE colon; complement; inflammation; inflammatory bowel disease ID INFLAMMATORY-BOWEL-DISEASE; DECAY-ACCELERATING FACTOR; ULCERATIVE-COLITIS; CROHNS-DISEASE; ACTIVATED COMPLEMENT; DENDRITIC CELLS; MURINE MODEL; MICE; C5A; EXPRESSION AB The role of complement in inflammatory bowel disease (IBD) has been studied primarily using acute models, and it is unclear how complement affects processes in more relevant chronic models of IBD in which modulation of adaptive immunity and development of fibrosis have pathogenic roles. Using mice deficient in C1q/mannose-binding lectin (MBL) or C3, we demonstrated an important role for these opsonins and/or the classical pathway C3 convertase in providing protection against mucosal injury and infection in a model of chronic dextran sulphate sodium (DSS)-induced colitis. In contrast, deficiency of the alternative pathway (fB(-/-) mice) had significantly less impact on injury profiles. Consequently, the effect of a targeted inhibitor of the alternative pathway was investigated in a therapeutic protocol. Following the establishment of colitis, mice were treated with CR2-fH during subsequent periods of DSS treatment and acute injury (modelling relapse). CR2-fH significantly reduced complement activation, inflammation and injury in the colon, and additionally reduced fibrosis. Alternative pathway inhibition also altered the immune response in the chronic state in terms of reducing numbers of B cells, macrophages and mature dendritic cells in the lamina propria. This study indicates an important role for the alternative pathway of complement in the pathogenesis and the shaping of an immune response in chronic DSS-induced colitis, and supports further investigation into the use of targeted alternative pathway inhibition for the treatment of IBD. C1 [Elvington, M.; Schepp-Berglind, J.; Tomlinson, S.] Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA. [Tomlinson, S.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave,BSB 201, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU Crohn's and Colitis Foundation of America; National Institutes of Health [T32 AR050958] FX This work was supported by a grant from the Crohn's and Colitis Foundation of America (to ST) and National Institutes of Health Training Grant T32 AR050958 (to J. S. B.). We thank Emily Paulling for histology work and expert technical assistance. NR 34 TC 4 Z9 4 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAR PY 2015 VL 179 IS 3 BP 500 EP 508 DI 10.1111/cei.12464 PG 9 WC Immunology SC Immunology GA CC0PQ UT WOS:000350038400013 PM 25293413 ER PT J AU Bernard, B Sweeney, CJ AF Bernard, Brandon Sweeney, Christopher J. TI Management of Metastatic Hormone-Sensitive Prostate Cancer SO CURRENT UROLOGY REPORTS LA English DT Article DE Metastatic hormone-sensitive prostate cancer; Androgen deprivation therapy; Chemohormonal therapy; Bone health ID ANDROGEN-DEPRIVATION THERAPY; PHASE-III TRIAL; OPEN-LABEL; DEGARELIX; INTERMITTENT; MONOTHERAPY; DOCETAXEL; MEN; MITOXANTRONE; PREDNISONE AB In 2014, prostate cancer will affect roughly 15% of American men during their lifetimes with about 230,000 new cases and 29,000 deaths per year. If required, most can be treated with curative surgery or radiotherapy. Upon relapse, androgen deprivation therapy (intermittent or continuous) is the cornerstone of treatment for hormone-sensitive disease. Response is variable and treatment is associated with a significant risk of toxicity. Recently, significant advances in survival have been demonstrated with chemohormonal therapy in men with high-volume disease. In addition, new findings have informed the approach to preventing bone complications in patients on therapy for metastatic hormone-sensitive prostate cancer. Devising clinical prediction tools and biomarkers is needed to select patients most likely to benefit from certain therapies and allow for a personalized approach. C1 [Bernard, Brandon; Sweeney, Christopher J.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Sweeney, CJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1230, Boston, MA 02215 USA. EM brandond_bernard@dfci.harvard.edu; christopher_sweeney@dfci.harvard.edu NR 36 TC 2 Z9 2 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1527-2737 J9 CURR UROL REP JI Curr. Urol. Rep. PD MAR PY 2015 VL 16 IS 3 AR UNSP 14 DI 10.1007/s11934-015-0488-8 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CC0VU UT WOS:000350057000007 PM 25677237 ER PT J AU McCully, KS AF McCully, Kilmer S. TI Homocysteine and the pathogenesis of atherosclerosis SO EXPERT REVIEW OF CLINICAL PHARMACOLOGY LA English DT Review DE atherosclerosis; homocysteine; lipoprotein; microorganisms; oxidative phosphorylation; oxidative stress; thioretinaco; thioretinamide ID RANDOMIZED CONTROLLED-TRIAL; B-VITAMIN THERAPY; CYSTATHIONINE BETA-SYNTHASE; HYDROGEN-SULFIDE; CHEMICAL PATHOLOGY; VASCULAR-DISEASE; THIOLACTONE METABOLISM; PROTEOGLYCAN STRUCTURE; MYOCARDIAL-INFARCTION; DIABETIC-NEPHROPATHY AB The homocysteine theory of arteriosclerosis was discovered by study of arteriosclerotic plaques occurring in homocystinuria, a disease caused by deficiencies of cystathionine synthase, methionine synthase or methylenetetrahydrofolate reductase. According to the homocysteine theory, metabolic and nutritional abnormalities leading to elevation of plasma homocysteine cause atherosclerosis in the general population without these rare enzymatic abnormalities. Through studies of metabolism of homocysteine thiolactone, the anhydride of homocysteine, in cell cultures from homocystinuric children, the pathway for synthesis of sulfate was found to be dependent upon thioretinamide, the amide formed from retinoic acid and homocysteine thiolactone. Two molecules of thioretinamide form the complex thioretinaco with cobalamin, and oxidative phosphorylation is catalyzed by reduction of oxygen, which is bound to thioretinaco ozonide, by electrons from electron transport particles. Atherogenesis is attributed to formation of aggregates of homocysteinylated lipoproteins with microorganisms, which obstruct the vasa vasorum during formation of arterial vulnerable plaques. C1 [McCully, Kilmer S.] VA Boston Healthcare Syst, Pathol & Lab Med Serv, West Roxbury, MA 02132 USA. [McCully, Kilmer S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP McCully, KS (reprint author), VA Boston Healthcare Syst, Pathol & Lab Med Serv, 1400 Vet Foreign Wars Pkwy, West Roxbury, MA 02132 USA. EM kilmer.mccully@va.gov RI McCully, Kevin/P-5141-2015 OI McCully, Kevin/0000-0001-9850-487X FU US Department of Veterans Affairs FX The preparation of this article was supported by the US Department of Veterans Affairs solely by salary. The author has 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 76 TC 16 Z9 23 U1 1 U2 27 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1751-2433 EI 1751-2441 J9 EXPERT REV CLIN PHAR JI Expert Rev. Clin. Pharmacol. PD MAR PY 2015 VL 8 IS 2 BP 211 EP 219 DI 10.1586/17512433.2015.1010516 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CC0JW UT WOS:000350022600007 PM 25653125 ER PT J AU Brauns, T Leblanc, P Gelfand, JA Poznanski, M AF Brauns, Timothy Leblanc, Pierre Gelfand, Jeffrey A. Poznanski, Mark TI Could mycobacterial Hsp70-containing fusion protein lead the way to an affordable therapeutic cancer vaccine? SO EXPERT REVIEW OF VACCINES LA English DT Review DE antigen presenting cells; cancer treatment costs; cancer vaccine; heat shock protein; immunotherapy; mesothelioma; ovarian cancer; tumor associated antigens ID HEAT-SHOCK PROTEINS; DENDRITIC CELL STIMULATION; TUMOR-NECROSIS-FACTOR; T-CELLS; ANTIGEN PRESENTATION; CROSS-PRESENTATION; PEPTIDE VACCINES; IMMUNE-RESPONSE; HUMAN HEAT-SHOCK-PROTEIN-60; ENDOPLASMIC-RETICULUM AB Cancer vaccine development efforts have recently gained momentum, but most vaccines showing clinical impact in human trials tend to be based on technology approaches that are very costly and difficult to produce at scale. With the projected doubling of the incidence of cancer and its related cost of care in the U.S. over the next two decades, the widespread clinical use of such vaccines will prove difficult to justify. Heat shock protein-based vaccines have shown the potential to elicit clinically meaningful immunologic responses in cancer, but the predominant development approach - heat shock protein-peptide complexes derived from a patient's own tumor - face similar challenges of cost and scalability. New innovative modalities for deploying heat shock proteins in cancer vaccines may open the door to vaccines that can generate potent cytotoxic responses against multiple tumor targets and can be made in a cost-effective and scalable manner. C1 [Brauns, Timothy; Leblanc, Pierre; Poznanski, Mark] Massachusetts Gen Hosp, Vaccine & Immunotherapy Ctr, Charlestown, MA 02129 USA. [Gelfand, Jeffrey A.] Massachusetts Gen Hosp, Vaccine & Immunotherapy Ctr, Boston, MA 02114 USA. RP Poznanski, M (reprint author), Massachusetts Gen Hosp, Vaccine & Immunotherapy Ctr, 149 13th St,Mailstop 149-5-5425, Charlestown, MA 02129 USA. EM mpoznansky@partners.org FU Edmund C. Lynch Jr. Cancer Fund; Arthur Luxenberg Esq.; Perry Weitz Esq.; Friends of VIC Fund FX This manuscript is dedicated to the memory of Janet Gelfand, a victim of ovarian cancer. The authors gratefully acknowledge the support that allowed for the original research discussed in this manuscript to be performed: The Edmund C. Lynch Jr. Cancer Fund, Arthur Luxenberg Esq., Perry Weitz Esq., and the Friends of VIC Fund. NR 84 TC 1 Z9 1 U1 1 U2 6 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD MAR PY 2015 VL 14 IS 3 BP 435 EP 446 DI 10.1586/14760584.2015.979797 PG 12 WC Immunology SC Immunology GA CC0UM UT WOS:000350052800010 PM 25496347 ER PT J AU Gray, ST Herr, MW Sethi, RKV Diercks, G Lee, L Curry, W Chan, AN Clark, J Holbrook, EH Rocco, J Sadow, PM Lin, DT AF Gray, Stacey T. Herr, Marc W. Sethi, Rosh K. V. Diercks, Gillian Lee, Linda Curry, William Chan, Annie Clark, John Holbrook, Eric H. Rocco, James Sadow, Peter M. Lin, Derrick T. TI Treatment outcomes and prognostic factors, including human papillomavirus, for sinonasal undifferentiated carcinoma: A retrospective review SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE sinonasal undifferentiated carcinoma; p16; human papillomavirus; sinonasal malignancy; treatment ID SQUAMOUS-CELL CARCINOMA; IN-SITU HYBRIDIZATION; OROPHARYNGEAL CANCER; P16 EXPRESSION; NECK TUMORS; ORAL-CAVITY; HEAD; EXPERIENCE; SURVIVAL; DISTINCT AB BackgroundSinonasal undifferentiated carcinoma (SNUC) is a high-grade, aggressive neoplasm. Low incidence and poor outcomes make identification of prognostic factors and treatment standardization difficult. Similarly, little is known regarding the association of human papillomavirus (HPV) with SNUC. MethodsA retrospective review was conducted. Extracted information included treatment received, tumor recurrence, patient survival, p16 expression, and HPV status. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). Survival trends were compared using the log-rank test. ResultsNineteen patients received multimodality treatment for SNUC. Five-year OS and DFS rates were 45.2% and 50.7%, respectively, with no significant difference between treatment types. Tumors from 11 patients were p16-positive and 9 of these were also HPV-positive. Kaplan-Meier analysis demonstrated improved survival. ConclusionOur series demonstrates a higher prevalence of HPV in SNUC than previously reported. HPV-positive SNUCs may benefit from improved survival and should be investigated further in future studies. (c) 2014 Wiley Periodicals, Inc. Head Neck 37: 366-374, 2015 C1 [Gray, Stacey T.; Herr, Marc W.; Diercks, Gillian; Lee, Linda; Holbrook, Eric H.; Rocco, James; Sadow, Peter M.; Lin, Derrick T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Gray, Stacey T.; Herr, Marc W.; Curry, William; Chan, Annie; Clark, John; Holbrook, Eric H.; Rocco, James; Lin, Derrick T.] Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Cranial Base Ctr, Boston, MA 02114 USA. [Sethi, Rosh K. V.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Curry, William] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Chan, Annie] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Clark, John] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Herr, MW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Div Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM marc.w.herr@gmail.com NR 47 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD MAR PY 2015 VL 37 IS 3 BP 366 EP 374 DI 10.1002/hed.23606 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CB9TG UT WOS:000349975100011 PM 24421248 ER PT J AU Palombo, DJ Keane, MM Verfaellie, M AF Palombo, Daniela J. Keane, Margaret M. Verfaellie, Mieke TI The Medial Temporal Lobes Are Critical for Reward-Based Decision Making Under Conditions That Promote Episodic Future Thinking SO HIPPOCAMPUS LA English DT Article DE hippocampus; amnesia; temporal discounting; delay discounting; mental time travel ID MENTAL TIME-TRAVEL; ORBITOFRONTAL CORTEX; VENTRAL HIPPOCAMPUS; IMPULSIVE CHOICE; SUBJECTIVE VALUE; MEMORY; DELAY; AMNESIA; RATS; PERSPECTIVE AB In the present study, we investigated the effect of medial temporal lobe (MTL) damage on human decision making in the context of reward-based intertemporal choice. During intertemporal choice, humans typically devalue (or discount) a future reward to account for its delayed arrival (e.g., preferring $30 now over $42 in 2 months), but this effect is attenuated when participants engage in episodic future thinking, i.e., project themselves into the future to imagine a specific event. We hypothesized that this attenuation would be selectively impaired in amnesic patients, who have deficits in episodic future thinking. Replicating previous work, in a standard intertemporal choice task, amnesic patients showed temporal discounting indices similar to healthy controls. Consistent with our hypothesis, while healthy controls demonstrated attenuated temporal discounting in a condition that required participants first to engage in episodic future thinking (e.g., to imagine spending $42 at a theatre in 2 months), amnesic patients failed to demonstrate this effect. Moreover, as expected, amnesic patients' narratives were less episodically rich than those of controls. These findings extend the range of tasks that are shown to be MTL dependent to include not only memory-based decision-making tasks but also future-oriented ones. (c) 2014 Wiley Periodicals, Inc. C1 [Palombo, Daniela J.; Keane, Margaret M.; Verfaellie, Mieke] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Palombo, Daniela J.; Keane, Margaret M.; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02130 USA. [Keane, Margaret M.] Wellesley Coll, Dept Psychol, Wellesley, MA 02481 USA. RP Palombo, DJ (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr, 150 South Huntington Ave,151-A, Boston, MA 02130 USA. EM palombo@bu.edu OI Palombo, Daniela/0000-0001-8082-3522 FU National Institutes of Mental Health [MH093431]; Clinical Science Research and Development Service of the Department of Veterans Affairs [IO1 CX000925]; Canadian Institutes of Health Research FX Grant sponsor: National Institutes of Mental Health; Grant number: MH093431; Grant sponsor: Clinical Science Research and Development Service of the Department of Veterans Affairs; Grant number: IO1 CX000925; Grant sponsor: Canadian Institutes of Health Research. NR 40 TC 20 Z9 20 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PD MAR PY 2015 VL 25 IS 3 BP 345 EP 353 DI 10.1002/hipo.22376 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CB9TM UT WOS:000349975900006 PM 25284804 ER PT J AU Kaplan, AB Kozin, ED Puram, SV Owoc, MS Shah, PV Hight, AE Sethi, RKV Remenschneider, AK Lee, DJ AF Kaplan, Alyson B. Kozin, Elliott D. Puram, Sidharth V. Owoc, Maryanna S. Shah, Parth V. Hight, A. E. Sethi, Rosh K. V. Remenschneider, Aaron K. Lee, Daniel J. TI Auditory brainstem implant candidacy in the United States in children 0-17 years old SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Auditory brainstem implant; Pediatric; Neuroprosthesis; Cochlear implant; Cochlear abnormalities; Cochlear nerve abnormalities ID SENSORINEURAL HEARING-LOSS; INNER-EAR MALFORMATIONS; BONE COMPUTED-TOMOGRAPHY; COCHLEAR IMPLANTATION; NERVE DEFICIENCY; NUCLEUS IMPLANT; DEAF-CHILDREN; APLASIA; PERFORMANCE; HYPOPLASIA AB Objectives: The auditory brainstem implant (ABI) is an option for hearing rehabilitation in profoundly deaf patients ineligible for cochlear implantation. Over the past decade, surgeons have begun implanting ABIs in pediatric patients who are unable to receive cochlear implants due to congenital or acquired malformations of the inner ear. No study has examined the potential population-level demand for ABIs in the United States (US). Herein, we aim to quantify the potential need for pediatric ABIs. Methods: A systematic literature review was conducted to identify studies detailing the rates of congenital cochlear and/or cochlear nerve (CN) anomalies. Absolute indications for ABI include bilateral cochlea or CN aplasia (Group A), and relative indications for ABI include bilateral cochlea or CN hypoplasia (Group B). Data was subsequently correlated to the US Census Bureau, the National Health Interview Survey, and the Gallaudet Research Institute to provide an estimation of pediatric ABI candidates. Results: Eleven studies documented rates of bilateral findings. Bilateral cochlea aplasia was identified in 0-8.7% of patients and bilateral CN aplasia in 0-4.8% of patients (Group A). Bilateral cochlea hypoplasia was identified in 0-8.7% of patients and bilateral CN hypoplasia in 0-5.4% of patients (Group B). Using population-level sensorineural hearing loss data, we roughly estimate 2.1% of potential implant candidates meet absolute indications for an ABI in the United States. Conclusion: Congenital cochlear and cochlear nerve anomalies are exceedingly rare. This study provides the first preliminary estimate of cochlea and CN aplasia/hypoplasia at the population level albeit with limitations based on available data. These data suggest the need for dedicated ABI centers to focus expertise and management. (C) 2015 Published by Elsevier Ireland Ltd. C1 [Kaplan, Alyson B.; Kozin, Elliott D.; Puram, Sidharth V.; Owoc, Maryanna S.; Shah, Parth V.; Hight, A. E.; Sethi, Rosh K. V.; Remenschneider, Aaron K.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kaplan, Alyson B.; Kozin, Elliott D.; Puram, Sidharth V.; Owoc, Maryanna S.; Shah, Parth V.; Hight, A. E.; Sethi, Rosh K. V.; Remenschneider, Aaron K.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Lee@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 FU NIDCD NIH HHS [T32 DC000020] NR 52 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD MAR PY 2015 VL 79 IS 3 BP 310 EP 315 DI 10.1016/j.ijporl.2014.11.023 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA CC2OF UT WOS:000350183800006 PM 25577282 ER PT J AU Langevin, HM Schnyer, R MacPherson, H Davis, R Harris, RE Napadow, V Wayne, PM Milley, RJ Lao, LX Stener-Victorin, E Kong, JT Hammerschlag, R AF Langevin, Helene M. Schnyer, Rosa MacPherson, Hugh Davis, Robert Harris, Richard E. Napadow, Vitaly Wayne, Peter M. Milley, Ryan J. Lao, Lixing Stener-Victorin, Elisabet Kong, Jiang-Ti Hammerschlag, Richard CA Soc Acupuncture Res TI Manual and Electrical Needle Stimulation in Acupuncture Research: Pitfalls and Challenges of Heterogeneity SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID LOW-BACK-PAIN; NERVE-STIMULATION; AURICULAR ELECTROACUPUNCTURE; ANALGESIA; METAANALYSIS; POINT; RAT; MODULATION; NALOXONE; BRAIN AB In the field of acupuncture research there is an implicit yet unexplored assumption that the evidence on manual and electrical stimulation techniques, derived from basic science studies, clinical trials, systematic reviews, and meta-analyses, is generally interchangeable. Such interchangeability would justify a bidirectional approach to acupuncture research, where basic science studies and clinical trials each inform the other. This article examines the validity of this fundamental assumption by critically reviewing the literature and comparing manual to electrical acupuncture in basic science studies, clinical trials, and meta-analyses. The evidence from this study does not support the assumption that these techniques are interchangeable. This article also identifies endemic methodologic limitations that have impaired progress in the field. For example, basic science studies have not matched the frequency and duration of manual needle stimulation to the frequency and duration of electrical stimulation. Further, most clinical trials purporting to compare the two types of stimulation have instead tested electroacupuncture as an adjunct to manual acupuncture. The current findings reveal fundamental gaps in the understanding of the mechanisms and relative effectiveness of manual versus electrical acupuncture. Finally, future research directions are suggested to better differentiate electrical from manual simulation, and implications for clinical practice are discussed. C1 [Langevin, Helene M.; Wayne, Peter M.] Harvard Univ, Sch Med, Osher Ctr Integrat Med, Boston, MA 02215 USA. [Schnyer, Rosa] Univ Texas Austin, Sch Nursing, Austin, TX 78712 USA. [MacPherson, Hugh] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Davis, Robert] Stromatec Inc, Burlington, VT USA. [Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Napadow, Vitaly] Harvard Univ, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Sch Med, Boston, MA 02215 USA. [Milley, Ryan J.; Hammerschlag, Richard] Oregon Coll Oriental Med, Portland, OR USA. [Lao, Lixing] Univ Hong Kong, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China. [Stener-Victorin, Elisabet] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. [Kong, Jiang-Ti] Stanford Univ, Sch Med, Dept Anesthesiol, Palo Alto, CA 94304 USA. RP Langevin, HM (reprint author), Harvard Univ, Brigham & Womens Hosp, Osher Ctr Integrat Med, Med Sch,Div Prevent Med, 900 Commonwealth Ave,Third Floor, Boston, MA 02215 USA. EM hlangevin@partners.org OI Stener-Victorin, Elisabet/0000-0002-3424-1502; Lao, Lixing/0000-0003-0198-9714 FU NIDA NIH HHS [T32 DA035165] NR 76 TC 9 Z9 10 U1 3 U2 17 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 MAR 1 PY 2015 VL 21 IS 3 BP 113 EP 128 DI 10.1089/acm.2014.0186 PG 16 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA CD0GR UT WOS:000350749200001 PM 25710206 ER PT J AU Nemani, N Santo, L Eda, H Cirstea, D Mishima, Y Patel, C O'Donnell, E Yee, A Raje, N AF Nemani, Neeharika Santo, Loredana Eda, Homare Cirstea, Diana Mishima, Yuko Patel, Chirayu O'Donnell, Elizabeth Yee, Andrew Raje, Noopur TI Role of Decorin in Multiple Myeloma (MM) Bone Marrow Microenvironment SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE MULTIPLE MYELOMA; OSTEOBLASTS; DECORIN; CCL3 ID DOWN-REGULATION; KINASE INHIBITOR; CARFILZOMIB; OSTEOBLASTS; MIP-1-ALPHA; MATRIX; MODEL AB Decorin is a small, leucine-rich proteoglycan found in the extracellular matrix of various connective tissues with potential effective tumor suppressive properties. Recent data suggest low levels of decorin in multiple myeloma (MM) patients compared to healthy volunteers, as well as in patients with osteolytic bone lesions compared to non-osteolytic lesions. In the present report, we investigated the role of decorin in the MM microenvironment or niche. Our data suggests that decorin is produced by osteoblasts (OBs) but not by MM cells. Furthermore, MM cells decrease OB-induced decorin secretion and this effect is mediated by CCL3. Importantly, neutralizing CCL3 from MM cells restores decorin levels in OBs as does proteasome inhibitors such as carfilzomib. These findings indicate that decorin may indirectly act as an antagonist to MM cell survival and that the interplay between MM and decorin may be an important target to explore in manipulating the tumor niche to inhibit tumorigenesis. (C) 2014 American Society for Bone and Mineral Research. C1 [Nemani, Neeharika; Santo, Loredana; Eda, Homare; Cirstea, Diana; Mishima, Yuko; Patel, Chirayu; O'Donnell, Elizabeth; Yee, Andrew; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Raje, N (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@mgh.harvard.edu FU Acetylon Pharmaceuticals Inc.; Eli Lilly FX NR is on the advisory board of Celgene, Novartis, Millennium, Onyx, and Amgen. NR has research funding from Acetylon Pharmaceuticals Inc. and Eli Lilly. The remaining authors state that they have no conflicts of interest. NR 20 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2015 VL 30 IS 3 BP 533 EP 538 DI 10.1002/jbmr.2371 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CC0YV UT WOS:000350066900017 ER PT J AU Boronat, S Mehan, WA Shaaya, EA Thibert, RL Caruso, P AF Boronat, Susana Mehan, William A. Shaaya, Elias A. Thibert, Ronald L. Caruso, Paul TI Hippocampal Abnormalities in Magnetic Resonance Imaging (MRI) of 15q Duplication Syndromes SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE CNV; duplication 15q11-q13; hippocampus; hippocampal malrotation; idic(15); neuroimaging; MR ID TEMPORAL-LOBE; EPILEPSY; MALFORMATIONS; ANOMALIES; CHILDREN; BRAIN AB Patients with 15q duplication syndromes, including isodicentric chromosome 15 and interstitial duplications, usually present with autism spectrum disorder, intellectual disability, and frequently epilepsy. Neuroimaging studies in these patients are typically reported as normal, but nonspecific findings such as thinning of the corpus callosum and increased pericerebral spaces have been reported. A review of brain magnetic resonance imaging (MRI) studies of 11 individuals seen at the Massachusetts General Hospital Dup15q Center was performed. Hippocampus morphology was specifically reviewed, as a recent neuropathologic study has found frequent hippocampal heterotopias and dysplasias in these disorders. Two subjects had unilateral hippocampal sclerosis and 6 had bilateral hippocampal malformations. Hypoplasia of the corpus callosum was present in 2 subjects. C1 [Boronat, Susana; Shaaya, Elias A.; Thibert, Ronald L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Boronat, Susana] Univ Autonoma Barcelona, Vall dHebron Hosp, Dept Pediat Neurol, E-08193 Barcelona, Spain. [Mehan, William A.; Caruso, Paul] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Boronat, S (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM susboronat@gmail.com FU BAE (beca de ampliacion de estudios) grant from the Carlos III Institute, Spain FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: SB is supported by a BAE (beca de ampliacion de estudios) grant from the Carlos III Institute, Spain. NR 22 TC 4 Z9 4 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 EI 1708-8283 J9 J CHILD NEUROL JI J. Child Neurol. PD MAR PY 2015 VL 30 IS 3 BP 333 EP 338 DI 10.1177/0883073814538669 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA CB9VY UT WOS:000349982900010 PM 24985752 ER PT J AU Chen, L Deng, WJ Thomas, RW McMullin, DD Lo Eng, H Buonanno, FS Ning, MM AF Chen, Lei Deng, Wenjun Thomas, Wickham R. McMullin, David D. Lo Eng, H. Buonanno, Ferdinando S. Ning, Mingming TI CLINICAL CHARACTERISTICS OF PFO STROKE IN PREGNANCY SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Chen, Lei] Sichuan Univ, West China Hosp, Chengdu 610064, Sichuan, Peoples R China. [Chen, Lei; Deng, Wenjun; Thomas, Wickham R.; McMullin, David D.; Lo Eng, H.; Buonanno, Ferdinando S.; Ning, Mingming] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2015 VL 63 IS 3 MA MP5 BP 573 EP 573 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CC1RM UT WOS:000350120400035 ER PT J AU Chen, L Deng, WJ Wickham, TR McMullin, DD Lo Eng, H Buonanno, FS Ning, MM AF Chen, Lei Deng, Wenjun Wickham, Thomas R. McMullin, David D. Lo Eng, H. Buonanno, Ferdinando S. Ning, Mingming TI PREGNANCY OUTCOMES FOLLOWING PFO RELATED STROKE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Chen, Lei] Sichuan Univ, West China Hosp, Chengdu 610064, Sichuan, Peoples R China. [Chen, Lei; Deng, Wenjun; Wickham, Thomas R.; McMullin, David D.; Lo Eng, H.; Buonanno, Ferdinando S.; Ning, Mingming] Mass Gen Hosp, Boston, MA USA. NR 0 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 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2015 VL 63 IS 3 MA MP8 BP 574 EP 574 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CC1RM UT WOS:000350120400038 ER PT J AU Deng, WJ Wickham, T Feeney-Heinzelmann, K Chen, L Inglessis, I Palacios, I Buonanno, F Lo, E Ning, MM AF Deng, Wenjun Wickham, Thomas Feeney-Heinzelmann, Kathleen Chen, Lei Inglessis, Ignacio Palacios, Igor Buonanno, Ferdinando Lo, Eng Ning, MingMing TI PFO CLOSURE REDUCES HIGH HOMOCYSTEINE LEVEL IN STROKE PATIENTS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Deng, Wenjun; Wickham, Thomas; Feeney-Heinzelmann, Kathleen; Chen, Lei; Inglessis, Ignacio; Palacios, Igor; Buonanno, Ferdinando; Lo, Eng; Ning, MingMing] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2015 VL 63 IS 3 MA P1 BP 581 EP 582 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CC1RM UT WOS:000350120400061 ER PT J AU Fuchs, HF Broderick, RC Harnsberger, CR Chang, DC Sandler, BJ Jacobsen, GR Horgan, S AF Fuchs, Hans F. Broderick, Ryan C. Harnsberger, Cristina R. Chang, David C. Sandler, Bryan J. Jacobsen, Garth R. Horgan, Santiago TI Benefits of Bariatric Surgery Do Not Reach Obese Men SO JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES LA English DT Article ID UNITED-STATES; GENDER; TRENDS; WOMEN; DISSATISFACTION; PREVALENCE; THINNESS; OUTCOMES; ACCESS AB Background: Epidemiological studies have shown an equal gender distribution of obesity in the United States; however, literature suggests approximately 80% of patients undergoing bariatric surgery are female. The aim of this study is to identify factors that contribute to this gender disparity. Study Design: A retrospective analysis of the Nationwide Inpatient Sample was performed. Obese patients who underwent open or laparoscopic gastric bypass or sleeve gastrectomy were identified using International Classification of Diseases, 9th edition codes. Patients <18 years of age were excluded. Female gender was used as a dependent variable to determine factors that influence gender distribution. Multivariate analyses adjusted for age, race, state within the United States, Charlson Comorbidity Index, income level, and insurance status. Results: From 1998 to 2010, 190,705 patients underwent bariatric surgery (93% gastric bypass, 7% sleeve gastrectomy). Females made up 81.36% of the population. An 80% to 20% female to male distribution was maintained for every year (1998-2010) and was unchanged within individual states. Patients were more likely to be female if from a lower-income neighborhood or if African American or Hispanic (P<.05). Patients were less likely to be female with increasing age, more comorbidities, or private insurance (P<.05). Conclusions: The unequal gender distribution in bariatric surgery patients is influenced by demographic and socioeconomic factors. This disparity is narrowed in patients who are older and have more comorbidities, whereas the disparity is widened for certain races and lower incomes. Given the equal distribution of obesity in the United States, the widespread gender gap in bariatric surgery may suggest an underuse in obese men. C1 [Fuchs, Hans F.; Broderick, Ryan C.; Harnsberger, Cristina R.; Chang, David C.; Sandler, Bryan J.; Jacobsen, Garth R.; Horgan, Santiago] Univ Calif San Diego, Dept Surg, Ctr Future Surg, Div Minimally Invas Surg, San Diego, CA 92103 USA. [Fuchs, Hans F.] Univ Cologne, Dept Gen Surg, D-50931 Cologne, Germany. [Chang, David C.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fuchs, HF (reprint author), Univ Calif San Diego, Dept Surg, Ctr Future Surg, Div Minimally Invas Surg, 9500 Gilman Dr,MC 0740, La Jolla, CA 92093 USA. EM hfuchs@ucsd.edu NR 31 TC 9 Z9 9 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1092-6429 EI 1557-9034 J9 J LAPAROENDOSC ADV S JI J. Laparoendosc. Adv. Surg. Tech. PD MAR 1 PY 2015 VL 25 IS 3 BP 196 EP 201 DI 10.1089/lap.2014.0639 PG 6 WC Surgery SC Surgery GA CD1GU UT WOS:000350823800005 PM 25654317 ER PT J AU Shao, JX Nguyen, KL Natsuaki, Y Spottiswoode, B Hu, P AF Shao, Jiaxin Nguyen, Kim-Lien Natsuaki, Yutaka Spottiswoode, Bruce Hu, Peng TI Instantaneous Signal Loss Simulation (InSiL): An Improved Algorithm for Myocardial T-1 Mapping Using the MOLLI Sequence SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE T-1 mapping; MR relaxometry; quantitative MRI; myocardial scar imaging ID INVERSION-RECOVERY MOLLI; MAGNETIZATION-TRANSFER; LOOK-LOCKER; PULSE SEQUENCE; HEART-FAILURE; T1; QUANTIFICATION; VOLUME; ATHEROSCLEROSIS; RELAXATION AB PurposeTo propose a T-1 mapping algorithm for the modified Look-Locker inversion-recovery (MOLLI) sequence that can improve T-1 estimation accuracy. Materials and MethodsThe modified T-1 mapping algorithm (InSiL) is based on the simulation of MOLLI signal evolution and simulates the longitudinal magnetization signal perturbation by each single-shot image acquisition in MOLLI as an instantaneous signal loss. InSiL was evaluated against original MOLLI using Bloch simulations, phantom studies, and in 15 healthy volunteers at 1.5T. ResultsIn phantom studies, the maximum absolute error by InSiL is less than 2%, while that by MOLLI is more than 20% for T-1 values from 221 msec to 1539 msec. The benefit of InSiL is greatest at heart rate (HR) >80 bpm and T-1 >1000 msec, and InSiL reduced MOLLI T-1 error from 14.94.5% to 0.4 +/- 0.3%. Average InSiL-derived native myocardial T-1 values at 1.5T in healthy volunteers were significantly higher than MOLLI-derived values by 236.9 +/- 11.7 msec (1160.3 +/- 25.1 msec vs. 923.4 +/- 22.3 msec, P<0.001) at an average HR of 65.1 +/- 14.7 bpm. ConclusionThe proposed InSiL approach yields better T-1 mapping accuracy than MOLLI, and is less sensitive to HR variation in tissues with longer T-1 values. J. Magn. Reson. Imaging 2015;41:721-729. (c) 2014 Wiley Periodicals, Inc. C1 [Shao, Jiaxin; Nguyen, Kim-Lien; Hu, Peng] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Nguyen, Kim-Lien] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA. [Nguyen, Kim-Lien] Vet Affairs Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA USA. [Natsuaki, Yutaka; Spottiswoode, Bruce] Siemens Healthcare, Chicago, IL USA. [Hu, Peng] Univ Calif Los Angeles, Biomed Phys Interdept Grad Program, Los Angeles, CA USA. RP Hu, P (reprint author), Dept Radiol Sci, 300 UCLA Med Plaza Suite B119, Los Angeles, CA 90095 USA. EM penghu@mednet.ucla.edu RI Shao, Jiaxin/S-3993-2016 OI Shao, Jiaxin/0000-0001-9998-3622 NR 31 TC 2 Z9 2 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAR PY 2015 VL 41 IS 3 BP 721 EP 729 DI 10.1002/jmri.24599 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CB9QT UT WOS:000349967700018 PM 24677371 ER PT J AU Ives-Erickson, J Duffy, ME Jones, DA AF Ives-Erickson, Jeanette Duffy, Mary E. Jones, Dorothy A. TI Development and Psychometric Evaluation of the Patient Care Associates' Work Environment Scale SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID RETENTION AB OBJECTIVE: The purpose of this study is to examine the psychometric properties of the Patient Care Associates' Work Environment Scale (PCA-WES). BACKGROUND: Few studies exist examining patient care associates (PCAs) working in acute care settings, and no instruments are available to examine the impact of the work environment on their practice. METHODS: A psychometric evaluation using a nonprobability purposive sample of 390 PCAs was undertaken. RESULTS: Cronbach's alpha internal consistency reliability of the total score was .95. Principal components analysis with varimax rotation and Kaiser normalization identified 5 components that accounted for 57.2% of variance and confirmed the original theoretical structure. The resulting 35-item scale had subscale Cronbach's alpha reliability estimates that ranged from .84 to .93. CONCLUSIONS: The multidimensional PCA-WES is a psychometrically sound measure of 5 components of the PCA practice environment in the acute care setting and is sufficiently reliable and valid for use as independent subscales in healthcare research. C1 [Ives-Erickson, Jeanette; Duffy, Mary E.; Jones, Dorothy A.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Duffy, ME (reprint author), Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, 275 Cambridge St, Boston, MA 02114 USA. EM pointjude@verizon.net NR 12 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 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAR PY 2015 VL 45 IS 3 BP 139 EP 144 DI 10.1097/NNA.0000000000000173 PG 6 WC Nursing SC Nursing GA CB9VG UT WOS:000349980900006 PM 25689499 ER PT J AU Ricci, JA Desai, NS Vendemia, N AF Ricci, Joseph A. Desai, Naman S. Vendemia, Nicholas TI Correction of a Contour Deformity Associated With Frontal Pneumosinus Dilatans Using Surgical Navigation Technology SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ETIOLOGY; SINUS AB Pneumosinus dilatans (PD) is a pathologic hyperaeration of the paranasal sinuses of unknown etiology. Although benign itself, PD has been associated with a number of serious concomitant conditions, including meningioma, optic nerve tumors, and visual loss. Patients with PD often present with cosmetic complaints, desiring recontouring of the facial bones to achieve an improved appearance of the face. The present case illustrates one of the first attempts at intraoperative surgical navigation to map the frontal sinus during correction of the facial deformity caused by PD. The navigation device was used to give the surgical team real-time information during the case to prevent violation of the posterior table of the frontal sinus, allowing for facial bone contouring to occur in a more efficient and safer manner by way of accurate osteotomy placement with no wasted bone for reconstruction and no accidental intracranial involvement. (C) 2015 American Association of Oral and Maxillofacial Surgeons C1 [Ricci, Joseph A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Plast Surg, Boston, MA USA. [Desai, Naman S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Vendemia, Nicholas] Manhattan Aesthet Surg, New York, NY USA. RP Ricci, JA (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, 55 Fruit St,WACC 435, Boston, MA 02114 USA. EM jaricci@partners.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2015 VL 73 IS 3 BP 529 EP 533 DI 10.1016/j.joms.2014.08.023 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CB6UM UT WOS:000349762200023 PM 25488312 ER PT J AU Menendez, ME Ring, D AF Menendez, Mariano E. Ring, David TI Failure to Rescue After Proximal Femur Fracture Surgery SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE failure to rescue; mortality; adverse events; inpatient; Elixhauser; complications; epidemiology; nationwide inpatient sample; trauma ID IN-HOSPITAL MORTALITY; QUALITY IMPROVEMENT PROGRAM; SURGICAL SAFETY CHECKLIST; NATIONWIDE INPATIENT SAMPLE; PAY-FOR-PERFORMANCE; CANCER-SURGERY; HIP FRACTURE; TO-RESCUE; OF-CARE; OUTCOMES AB Objectives: Failure to rescue (FTR)-death after a major adverse event-has recently been identified as an important determinant of variation in surgical mortality. We sought to identify patient and hospital characteristics associated with FTR after proximal femur fracture surgery, and to determine whether they are different from the predictors of the occurrence of adverse events. We also identified which adverse events are most highly associated with FTR. Methods: Among an estimated 287,959 patients with a surgically treated proximal femur fracture identified in the 2011 Nationwide Inpatient Sample, the overall adverse event rate was 22% and the FTR rate was 6.4%. Multivariable logistic regression modeling was used to identify independent predictors of FTR and adverse events. Results: Patient-specific variables influenced adverse event occurrence but exerted little or no influence on FTR. Hospitals located in rural areas were 14% less likely than urban hospitals to have adverse events [ odds ratio (OR): 0.86, 95% confidence interval (CI): 0.83-0.89], but 30% more likely to fail to rescue patients from adverse events (OR: 1.3, 95% CI: 1.2-1.5). Compared with teaching and large hospitals, nonteaching settings and institutions of smaller size were associated with decreased risk for adverse events, but similar risk for FTR. Lower hospital volume was a risk factor for adverse events and FTR. There was a more than 3-fold increased risk for death among patients with respiratory failure (OR: 5.4, 95% CI: 5.0-5.8), pulmonary embolism (OR: 3.6, 95% CI: 3.1-4.1), and myocardial infarction (OR: 3.0, 95% CI: 2.8-3.3). Conclusions: Because FTR is less affected by patient characteristics than morbidity, it might be a better measure of provider-specific performance in hip fracture surgery. Targeted initiatives aimed at improving the timely recognition and management of cardiorespiratory adverse events -particularly at rural hospitals-might be key to reducing mortality. C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 57 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0890-5339 EI 1531-2291 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD MAR PY 2015 VL 29 IS 3 BP E96 EP E102 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA CC1ZM UT WOS:000350144000003 PM 25233165 ER PT J AU Li, JW Morway, L Velasquez, A Weingart, SN Stuver, SO AF Li, Justin W. Morway, Laurinda Velasquez, Andrew Weingart, Saul N. Stuver, Sherri O. TI Perceptions of Medical Errors in Cancer Care: An Analysis of How the News Media Describe Sentinel Events SO JOURNAL OF PATIENT SAFETY LA English DT Article DE medical errors; news media; cancer patients ID PATIENT SAFETY; ADVERSE EVENTS; COVERAGE; INFORMATION AB Objective: To analyze the print news media's coverage of sentinel events involving cancer patients. Methods: Using LexisNexis (R), we identified English-language newspaper articles covering medical errors in cancer care between January 1, 2000, and December 31, 2010. Articles were coded for 3 major themes using a standardized abstraction instrument: narrative statements and point of view most prominently represented, attribution of blame, and orientation toward patient safety. We also abstracted country where the newspaper was published, type of error event, and extent of patient harm. Results: We analyzed 64 articles from 37 print newspaper syndications that circulated in 6 countries/regions. Reports of medical errors rarely were framed from the point of view of a safety expert or the responsible clinician (13% and 3%, respectively) compared with the patient and legal points of view (both 30%). Articles held individual clinicians (41%) and hospital systems (28%) responsible for most errors. Four in 10 articles failed to present medical errors as "systems'' problems. Article perspective varied considerably by country, with 53% of articles from the UK and 63% from Australia and New Zealand judged as negatively slanted compared with 14% in the United States and Canada. Conclusions: In reports of medical errors involving cancer patients, the news media regularly blame individual clinicians for mistakes and fail to present a systems-based understanding of these events. C1 [Li, Justin W.; Morway, Laurinda; Velasquez, Andrew; Weingart, Saul N.; Stuver, Sherri O.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02215 USA. RP Stuver, SO (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 450 Brookline Ave, Boston, MA 02215 USA. EM sherri_stuver@dfci.harvard.edu FU Center for Patient Safety, Dana-Farber Cancer Institute FX Center for Patient Safety, Dana-Farber Cancer Institute. NR 30 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 1549-8417 J9 J PATIENT SAF JI J. Patient Saf. PD MAR PY 2015 VL 11 IS 1 BP 42 EP 51 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CB9UV UT WOS:000349979700007 PM 24080724 ER PT J AU Hettmer, S Teot, LA Kozakewich, H Werger, AM Davies, KJ Fletcher, CDM Grier, HE Rodriguez-Galindo, C Wagers, AJ AF Hettmer, Simone Teot, Lisa A. Kozakewich, Harry Werger, Annette M. Davies, Kimberly J. Fletcher, Christopher D. M. Grier, Holcombe E. Rodriguez-Galindo, Carlos Wagers, Amy J. TI Myogenic Tumors in Nevoid Basal Cell Carcinoma Syndrome SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE fetal rhabdomyoma; rhabdomyosarcoma; PATCHED; nevoid basal cell carcinoma syndrome ID FETAL RHABDOMYOMA; NASOPHARYNGEAL RHABDOMYOSARCOMA; HEDGEHOG PATHWAY; GORLIN-SYNDROME; MOUSE MODEL; GENES AB In mice, activated Hedgehog (Hh) signaling induces tumors with myogenic differentiation. In humans, hyperactive Hh signaling due to germline PATCHED1 (PTCH1) mutations has been linked to nevoid basal cell carcinoma syndrome (NBCCS). We report an embryonal rhabdomyosarcoma in a 16-month-old girl with NBCCS and review the literature on myogenic neoplasms in NBCCS, including 8 fetal rhabdomyomas and 3 rhabdomyosarcomas. Of note, 3 population studies, including 255 individuals with NBCCS aged 4 months to 87 years, did not identify any myogenic tumors. Thus, myogenic tumors in NBCCS are rare and include both rhabdomyosarcomas and fetal rhabdomyomas. C1 [Hettmer, Simone; Werger, Annette M.; Davies, Kimberly J.; Grier, Holcombe E.; Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hettmer, Simone; Davies, Kimberly J.; Grier, Holcombe E.; Rodriguez-Galindo, Carlos] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA USA. [Teot, Lisa A.; Kozakewich, Harry] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Hettmer, Simone; Wagers, Amy J.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Hettmer, Simone; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. [Hettmer, Simone; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Fletcher, Christopher D. M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Hettmer, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM simone.hettmer@childrens.harvard.edu FU P.A.L.S. Bermuda/St. Baldrick's and the Alex's Lemonade Stand Foundation; Stand Up To Cancer-American Association for Cancer Research Innovative Research Grant [SU2C-AACR-IRG1111] FX Supported in part by P.A.L.S. Bermuda/St. Baldrick's and the Alex's Lemonade Stand Foundation (to S.H.), and by a Stand Up To Cancer-American Association for Cancer Research Innovative Research Grant, Grant Number SU2C-AACR-IRG1111. NR 21 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1077-4114 EI 1536-3678 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAR PY 2015 VL 37 IS 2 BP 147 EP 149 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CB8UD UT WOS:000349905900024 PM 24517962 ER PT J AU Reese, HE Vallejo, Z Rasmussen, J Crowe, K Rosenfield, E Wilhelm, S AF Reese, Hannah E. Vallejo, Zayda Rasmussen, Jessica Crowe, Katherine Rosenfield, Elizabeth Wilhelm, Sabine TI Mindfulness-based stress reduction for Tourette syndrome and chronic tic disorder: A pilot study SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Chronic tic disorder; Mindfulness; Psychosocial; Tourette syndrome; Treatment ID RANDOMIZED CONTROLLED-TRIAL; HABIT-REVERSAL; BEHAVIOR-THERAPY; MEDITATION; CHILDREN; INTERVENTION; ADOLESCENTS; SEVERITY; ADULTS; SCALE AB Objective: In this pilot study we sought to develop and test a modified form of mindfulness-based stress reduction (MBSR-tics) for the treatment of Tourette Syndrome (TS) and Chronic Tic Disorder (CTD). Our specific aims were: 1) To determine the feasibility and acceptability of an 8-week trial of MBSR-tics in individuals 16 and older with TS or CTD and 2) To determine the efficacy of an 8-week trial of MBSR-tics in individuals 16 and older with TS or CTD. Methods: Eighteen individuals age 16-67 completed an uncontrolled open trial of MBSR-tics. The intervention consisted of 8 weekly 2-hour classes and one 4 hour retreat in the fifth or sixth week of the program. Symptomatic assessments were performed at baseline, post-treatment, and one-month follow-up. Results: MBSR-tics proved to be a feasible and acceptable intervention. It resulted in significant improvement in tic severity and tic-related impairment. 58.8% of subjects were deemed treatment responders. Therapeutic gains were maintained at 1-month follow-up. Improvements in tic severity were correlated with increases in self-reported levels of mindfulness. Conclusions: This small open pilot study provides preliminary support for the feasibility, acceptability, and efficacy of MBSR-tics for individuals 16 or older with TS or CTD. A larger randomized controlled trial with blind assessment is necessary to confirm these initial, promising findings. (C) 2014 Elsevier Inc All rights reserved. C1 [Reese, Hannah E.; Vallejo, Zayda; Rasmussen, Jessica; Crowe, Katherine; Rosenfield, Elizabeth; Wilhelm, Sabine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. RP Reese, HE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. EM hreese@mgh.harvard.edu FU Tourette Syndrome Association (TSA) FX The present study was funded by a grant from the Tourette Syndrome Association (TSA) awarded to the first author. The TSA played no role in the study design, collection, analysis, or interpretation of the data, the writing of the report, or the decision to submit the article for publication. NR 30 TC 6 Z9 7 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD MAR PY 2015 VL 78 IS 3 BP 293 EP 298 DI 10.1016/j.jpsychores.2014.08.001 PG 6 WC Psychiatry SC Psychiatry GA CC2PE UT WOS:000350186300013 PM 25149879 ER PT J AU Banks, CA Knox, C Hunter, DA Mackinnon, SE Hohman, MH Hadlock, TA AF Banks, Caroline A. Knox, Christopher Hunter, Daniel A. Mackinnon, Susan E. Hohman, Marc H. Hadlock, Tessa A. TI Long-Term Functional Recovery after Facial Nerve Transection and Repair in the Rat SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE facial nerve transection and repair; facial paralysis; regeneration; whisking ID QUALITY-OF-LIFE; CRUSH INJURY; REGENERATION; STIMULATION; PARALYSIS; MODEL; WHISKING; SURGERY; NEURON AB Background The rodent model is commonly used to study facial nerve injury. Because of the exceptional regenerative capacity of the rodent facial nerve, it is essential to consider the timing when studying facial nerve regeneration and functional recovery. Short-term functional recovery data following transection and repair of the facial nerve has been documented by our laboratory. However, because of the limitations of the head fixation device, there is a lack of long-term data following facial nerve injury. The objective of this study was to elucidate the long-term time course and functional deficit following facial nerve transection and repair in a rodent model. Methods Adult rats were divided into group 1 (controls) and group 2 (experimental). Group 1 animals underwent head fixation, followed by a facial nerve injury, and functional testing was performed from day 7 to day 70. Group 2 animals underwent facial nerve injury, followed by delayed head fixation, and then underwent functional testing from months 6 to 8. Results There was no statistical difference between the average whisking amplitudes in group 1 and group 2 animals. Conclusion Functional whisking recovery 6 months after facial nerve injury is comparable to recovery within 1 to 4 months of transection and repair, thus the ideal window for evaluating facial nerve recovery falls within the 4 months after injury. C1 [Banks, Caroline A.; Knox, Christopher; Hohman, Marc H.] Harvard Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hunter, Daniel A.] Washington Univ, Sch Med, Dept Plast Surg, St Louis, MO USA. [Mackinnon, Susan E.] Washington Univ, Dept Surg, St Louis, MO USA. [Hadlock, Tessa A.] Mass Eye & Ear Infirm, Dept Otolaryngol, Facial Nerve Ctr, Boston, MA USA. RP Banks, CA (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Caroline_Banks@meei.harvard.edu FU NINDS NIH HHS [R01 NS071067] NR 28 TC 1 Z9 1 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X EI 1098-8947 J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD MAR PY 2015 VL 31 IS 3 BP 210 EP 216 DI 10.1055/s-0034-1395940 PG 7 WC Surgery SC Surgery GA CC2QD UT WOS:000350188800008 PM 25629206 ER PT J AU Kopple, JD Kim, JC Shapiro, BB Zhang, M Li, YA Porszasz, J Bross, R Feroze, U Upreti, R Kalantar-Zadeh, K AF Kopple, Joel D. Kim, Jun C. Shapiro, Bryan B. Zhang, Min Li, Yinan Porszasz, Janos Bross, Rachelle Feroze, Usama Upreti, Rajeev Kalantar-Zadeh, Kamyar TI Factors Affecting Daily Physical Activity and Physical Performance in Maintenance Dialysis Patients SO JOURNAL OF RENAL NUTRITION LA English DT Article ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; ANXIETY DISORDERS; DEPRESSION; EXERCISE; MORTALITY; METAANALYSIS; ASSOCIATION; POPULATION AB Maintenance hemodialysis (MHD) patients display reduced daily physical activity (DPA) and physical performance (PP). Previous studies did not differentiate the effects of kidney failure and MHD treatments from comorbidities as causes for reduced DPA and PP. In relatively healthy MHD patients and normal adults, we evaluated DPA and PP and examined relationships between DPA and PP and possible associations between anxiety or depression and DPA and PP. DPA, 6-minute walk distance (6-MWD), sit-to-stand (STS), and stair-climbing tests were measured in 72 MHD patients (40% diabetics) with limited comorbidities and 39 normal adults of similar age and gender mix. Anxiety and depression were measured by the Beck anxiety and depression inventories. DPA, time-averaged over 7 days, and all 3 PP tests were impaired in MHD patients, to about 60% to 70% of normal values (P < .0001 for each measurement). MHD patients spent more time sleeping or physically inactive (P < .0001) and less time in >= moderate activity (P < .0001). Adjusted DPA correlated with 6-MWD but not STS or stair-climbing. Anxiety and depression were identified in 43% and 33% of MHD patients and 2.5% and 5.1% of normals (P < .0001 for each comparison). Most of the impairment in DPA and PP tests were also observed in MHD patients without anxiety or depression. However, MHD patients with both anxiety and depression generally had the most impaired DPA and PP. In MHD patients, higher adjusted anxiety scores were correlated with impaired 6-MWD and STS, whereas adjusted average DPA was negatively correlated with depression (r = -0.33, P = .006) but not anxiety. DPA on the hemodialysis day (P = .01), day after dialysis (P = .03), and day 2 after dialysis (P = .03) each correlated negatively with degree of depression but not with anxiety. MHD patients displayed negative-adjusted correlations between anxiety and 6-MWD (P = .03) and STS (P = .04). In relatively healthy MHD patients, DPA and PP are substantially impaired and correlated with each other, even in patients without evidence for anxiety or depression. Anxiety and depression are common in MHD patients and are associated with further impairment in DPA and PP. (C) 2015 by the National Kidney Foundation, Inc. All rights reserved. C1 [Kopple, Joel D.; Kim, Jun C.; Shapiro, Bryan B.; Zhang, Min; Li, Yinan; Feroze, Usama; Upreti, Rajeev] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Nephrol & Hypertens, Torrance, CA 90509 USA. [Kopple, Joel D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kim, Jun C.] CHA Univ, CHA Gumi Med Ctr, Div Nephrol, Seoul, South Korea. [Feroze, Usama] Harvard South Shore Psychiat Residency Program, VA Boston Hlth Care Syst, Brockton, MA USA. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Div Nephrol & Hypertens, Irvine, CA USA. [Kopple, Joel D.; Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Porszasz, Janos] Harbor UCLA Med Ctr, Div Resp & Crit Care Physiol & Med, Rehabil Clin Trials Ctr, Torrance, CA 90509 USA. [Porszasz, Janos] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Zhang, Min] Tianjin Union Med Ctr, Div Nephrol, Tianjin, Peoples R China. [Li, Yinan] Xiamen Univ, Affiliated Hosp 1, Dept Nephrol, Xiamen, Peoples R China. [Kalantar-Zadeh, Kamyar] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Harold Simmons Ctr Kidney Dis Res & Epidemiol, Torrance, CA 90509 USA. [Bross, Rachelle] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, UCLA Clin & Translat Sci Inst, Torrance, CA 90509 USA. RP Kopple, JD (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, 1000 West Carson St C-1 Annex, Torrance, CA 90509 USA. EM jkopple@labiomed.org OI Porszasz, Janos/0000-0002-5823-0031; Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 31 TC 3 Z9 3 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 1051-2276 EI 1532-8503 J9 J RENAL NUTR JI J. Renal Nutr. PD MAR PY 2015 VL 25 IS 2 BP 217 EP 222 DI 10.1053/j.jrn.2014.10.017 PG 6 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA CB9NV UT WOS:000349959400026 PM 25701942 ER PT J AU von Keudell, A Sadoghi, P AF von Keudell, Arvind Sadoghi, Patrick TI A Response to the New England Journal of Medicine Article A Randomized Trial of Epidural Glucocorticoid Injections for Spinal Stenosis SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Letter C1 [von Keudell, Arvind] Harvard Med Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Sadoghi, Patrick] Med Univ Graz, Dept Orthopaed Surg, Graz, Austria. RP von Keudell, A (reprint author), Harvard Med Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1536-0652 EI 1539-2465 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD MAR PY 2015 VL 28 IS 2 BP 76 EP 76 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA CC1PS UT WOS:000350114200007 PM 25393664 ER PT J AU Stey, AM Russell, MM Hall, BL Lin, A Gibbons, MM Lawson, EH Zingmond, DS Ko, CY AF Stey, Anne M. Russell, Marcia M. Hall, Bruce L. Lin, Andy Gibbons, Melinda M. Lawson, Elise H. Zingmond, David S. Ko, Clifford Y. TI Is There Hospital Variation in Long-Term Incisional Hernia Repair after Abdominal Surgery? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY-OF-LIFE; ADMINISTRATIVE DATABASES; VETERANS-AFFAIRS; CLAIMS DATA; SURGICAL CARE; FOLLOW-UP; OUTCOMES; MEDICARE; COST; COMPLICATIONS AB BACKGROUND: Currently, hospital benchmarking organizations are often limited to short-term surgical quality comparisons among hospitals. The goal of this study was to determine whether long-term rates of incisional hernia repair after common abdominal operations could be used to compare hospital long-term surgical quality. STUDY DESIGN: This was a cohort study with up to 4 years of follow-up. Patients who underwent 1 of 5 common inpatient abdominal operations were identified in 2005-2008 American College of Surgeons NSQIP data linked to Medicare inpatient records. The main outcomes included occurrence of an incisional hernia repair. A multivariable, shared frailty Cox proportional hazards regression was used to compare each hospital's incisional hernia rate with the overall mean rate for all hospitals and control for American College of Surgeons NSQIP preoperative clinical variables. RESULTS: A total of 37,134 patients underwent 1 of 5 common inpatient abdominal operations, including colectomy, small bowel resection, ventral hernia repair, pancreatic resection, or cholecystectomy, at 1 of 216 hospitals participating in American College of Surgeons NSQIP during the 4-year period. There were 1,474 (4.0%) patients who underwent an incisional hernia repair, at a median follow-up time of 16 months (interquartile range 8 to 25 months) after initial abdominal surgery. After risk adjustment, there was no significant difference in the ratio of any one hospital's adjusted hazard rate for incisional hernia repair vs the average hospital adjusted hazard rate. CONCLUSIONS: Risk-adjusted hospital rates of incisional hernia repair do not vary significantly from the average. This suggests that incisional hernia repair might not be sensitive enough as a long-term quality metric for benchmarking hospital performance. (C) 2015 by the American College of Surgeons C1 [Stey, Anne M.] Mt Sinai Med Ctr, Icahn Sch Med, New York, NY 10029 USA. [Stey, Anne M.; Russell, Marcia M.; Lin, Andy; Gibbons, Melinda M.; Lawson, Elise H.; Zingmond, David S.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Russell, Marcia M.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Hall, Bruce L.] Washington Univ, Sch Med St Louis, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Olin Business Sch, St Louis, MO 63130 USA. [Hall, Bruce L.] Washington Univ St Louis, St Louis VA Med Ctr, Washington, DC USA. [Hall, Bruce L.] BJC Healthcare, St Louis, MO USA. [Hall, Bruce L.; Ko, Clifford Y.] Amer Coll Surg, Chicago, IL USA. RP Stey, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 10940 Wilshire Blvd,Ste 710, Los Angeles, CA 90024 USA. EM as013j@gmail.com FU Robert Wood Johnson Foundation Clinical Scholars Program; US Department of Veterans Affairs [70039]; American College of Surgeons FX Supported by the Robert Wood Johnson Foundation Clinical Scholars Program and the US Department of Veterans Affairs (grant no. 70039). Drs Hall and Ko are paid consultants for the American College of Surgeons. NR 41 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAR PY 2015 VL 220 IS 3 BP 313 EP U192 DI 10.1016/j.jamcollsurg.2014.11.011 PG 12 WC Surgery SC Surgery GA CB8WI UT WOS:000349912300010 PM 25542281 ER PT J AU Levy, C White, H AF Levy, Cari White, Heidi TI The AMDA Foundation Futures Program: Inspiring the Next Generation of Postacute and Long-Term Care Medical Directors SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Editorial Material C1 [Levy, Cari] Denver Vet Affairs Med Ctr, Dept Med, Div Hlth Care Policy & Res, Denver, CO 80220 USA. [Levy, Cari] Univ Colorado, Denver, CO 80220 USA. [White, Heidi] Duke Univ, Dept Med, Div Geriatr, Durham, NC USA. RP Levy, C (reprint author), Denver Vet Affairs Med Ctr, Dept Med, Div Hlth Care Policy & Res, 1055 Clermont St, Denver, CO 80220 USA. EM cari.levy@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 EI 1538-9375 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD MAR 1 PY 2015 VL 16 IS 3 BP 179 EP 180 DI 10.1016/j.jamda.2014.12.011 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA CC2LQ UT WOS:000350176900004 PM 25659619 ER PT J AU Mohajer, MA Darouiche, RO AF Mohajer, M. Al Darouiche, R. O. TI Re: Infections Associated with Inflatable Penile Prostheses SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 [Mohajer, M. Al; Darouiche, R. O.] Univ Arizona, Dept Med, Tucson, AZ 85724 USA. [Mohajer, M. Al; Darouiche, R. O.] Baylor Coll Med, Spinal Cord Injury & Med Care Lines, Infect Dis Sect, Michael E DeBakey & Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Mohajer, MA (reprint author), Univ Arizona, Dept Med, Tucson, AZ 85724 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD MAR PY 2015 VL 193 IS 3 BP 907 EP 907 DI 10.1016/j.juro.2014.12.043 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CB8IX UT WOS:000349873300051 ER PT J AU Carr, PL Gunn, CM Kaplan, SA Raj, A Freund, KM AF Carr, Phyllis L. Gunn, Christine M. Kaplan, Samantha A. Raj, Anita Freund, Karen M. TI Inadequate Progress for Women in Academic Medicine: Findings from the National Faculty Study SO JOURNAL OF WOMENS HEALTH LA English DT Article ID ORGANIZATIONAL-CLIMATE; CAREER SATISFACTION; GENDER-DIFFERENCES; ADVANCEMENT; PHYSICIANS; SCHOOL; COMPENSATION; PRODUCTIVITY; PERCEPTIONS; IMPACT AB Background: Women have entered academic medicine in significant numbers for 4 decades and now comprise 20% of full-time faculty. Despite this, women have not reached senior positions in parity with men. We sought to explore the gender climate in academic medicine as perceived by representatives to the Association of American Medical Colleges (AAMC) Group on Women in Medicine and Science (GWIMS) and Group on Diversity and Inclusion (GDI). Methods: We conducted a qualitative analysis of semistructured telephone interviews with GWIMS and GDI representatives and other senior leaders at 24 randomly selected medical schools of the 1995 National Faculty Study. All were in the continental United States, balanced for public/private status and AAMC geographic region. Interviews were audiotaped, transcribed, and organized into content areas before an inductive thematic analysis was conducted. Themes that were expressed by multiple informants were studied for patterns of association. Results: Five themes were identified: (1) a perceived wide spectrum in gender climate; (2) lack of parity in rank and leadership by gender; (3) lack of retention of women in academic medicine (the "leaky pipeline"); (4) lack of gender equity in compensation; and (5) a disproportionate burden of family responsibilities and work-life balance on women's career progression. Conclusions: Key informants described improvements in the climate of academic medicine for women as modest. Medical schools were noted to vary by department in the gender experience of women, often with no institutional oversight. Our findings speak to the need for systematic review by medical schools and by accrediting organizations to achieve gender equity in academic medicine. C1 [Carr, Phyllis L.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Gunn, Christine M.] Boston Univ, Sch Med, Dept Med, Womens Hlth Unit, Boston, MA 02118 USA. [Kaplan, Samantha A.] Boston Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. [Raj, Anita] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Freund, Karen M.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Freund, Karen M.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Carr, PL (reprint author), Massachusetts Gen Hosp, Yawkey 4B,55 Fruit St, Boston, MA 02114 USA. EM pcarr1@partners.org OI Gunn, Christine/0000-0003-3340-2834 FU National Institute of General Medical Science; Office of the Director, National Institutes of Health [R01 GM088470] FX Funding for the research reported in this article was supported by the National Institute of General Medical Science and the Office of the Director, National Institutes of Health, under award number R01 GM088470. NR 26 TC 18 Z9 18 U1 5 U2 21 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 MAR 1 PY 2015 VL 24 IS 3 BP 190 EP 199 DI 10.1089/jwh.2014.4848 PG 10 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 CD0GV UT WOS:000350749600004 PM 25658907 ER PT J AU Rosso, AL Sanders, JL Arnold, AM Boudreau, RM Hirsch, CH Carlson, MC Rosano, C Kritchevsky, SB Newman, AB AF Rosso, Andrea L. Sanders, Jason L. Arnold, Alice M. Boudreau, Robert M. Hirsch, Calvin H. Carlson, Michelle C. Rosano, Caterina Kritchevsky, Stephen B. Newman, Anne B. TI Multisystem Physiologic Impairments and Changes in Gait Speed of Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Gait; Physical function; Epidemiology ID CARDIOVASCULAR HEALTH; PHYSICAL FUNCTION; INCIDENT DISABILITY; BODY-COMPOSITION; WOMENS HEALTH; WALKING SPEED; ASSOCIATION; COMORBIDITY; MORTALITY; DECLINE AB Background: Slowed gait is an important health indicator in older adults but a single identifiable cause is often lacking. We assessed whether a summary index measuring impairments across multiple physiologic systems was associated with slowed gait in older individuals. Methods: Data from the Cardiovascular Health Study (n = 3,010) were used to assess associations between baseline physiologic index (measuring vasculature, brain, kidneys, lungs, and glucose metabolism; range 0-10 with 0-2 points/system and lower score indicating higher function) and annual gait speed (m/s) over 6 years. Participants with complete data on the physiologic index and at least two gait speed measures were included. Mean gait speed and 95% confidence intervals (CI) by category of index were calculated using mixed effects models. Results: Those with scores of three or higher on the index had significantly slower gait speed at baseline compared to those with scores of 0-2 (7-10: mean speed = 0.83 m/s, 95% CI: 0.80, 0.84; 0-2: mean speed = 1.01 m/s, 95% CI: 0.99, 1.03). Those with higher indices also had faster decline in gait speed compared to those with lower scores after adjustment for demographic and health characteristics (7-10: change in speed = -0.020 m/s/year, 95% CI: -0.024, -0.016; 0-2: change in speed = -0.010 m/s/year, 95% CI: -0.014, -0.006). Conclusions: Greater impairment across five organ systems was associated with slower gait speed and greater declines in gait speed over 6 years. Impairments accumulated over multiple physiologic systems may make older adults more vulnerable to slow gait speed. C1 [Rosso, Andrea L.; Boudreau, Robert M.; Rosano, Caterina; Newman, Anne B.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Sanders, Jason L.] Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Sanders, Jason L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Arnold, Alice M.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Hirsch, Calvin H.] Univ Calif Davis, Davis Med Ctr, Div Gen Med, Sacramento, CA 95817 USA. [Carlson, Michelle C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. RP Rosso, AL (reprint author), Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, 130 N Bellefield Ave, Pittsburgh, PA 15213 USA. EM alr143@pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Rosso, Andrea/0000-0001-5890-9856; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Boudreau, Robert/0000-0003-0162-5187 FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute on Aging (NIA) [AG023629]; NIA [T32-AG-000181] FX This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. Additional funding for this analysis came from a training grant from the NIA (T32-AG-000181). NR 31 TC 8 Z9 8 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2015 VL 70 IS 3 BP 317 EP 322 DI 10.1093/gerona/glu176 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CC1RZ UT WOS:000350122200006 PM 25380599 ER PT J AU Koyama, A Houston, DK Simonsick, EM Lee, JS Ayonayon, HN Shahar, DR Rosano, C Satterfield, S Yaffe, K AF Koyama, Alain Houston, Denise K. Simonsick, Eleanor M. Lee, Jung Sun Ayonayon, Hilsa N. Shahar, Danit R. Rosano, Caterina Satterfield, Suzanne Yaffe, Kristine TI Association Between the Mediterranean Diet and Cognitive Decline in a Biracial Population SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Epidemiology; Nutrition; Cognitive aging; Alzheimers; Cognition ID MENTAL-STATE-EXAM; ALZHEIMERS-DISEASE; CARDIOVASCULAR-DISEASE; ADHERENCE; RISK; DEMENTIA; HEALTH; MEDDIETSCORE; IMPAIRMENT; AMERICANS AB Background. Results from numerous studies suggest protective effects of the Mediterranean diet for cardiovascular disease, cancer, and mortality. Evidence for an association with a decreased risk of cognitive decline is less consistent and studies are limited by a lack of diversity in their populations. Methods. We followed 2,326 older adults (38.2% black, 51.3% female, aged 70-79 at baseline) over 8 years in a prospective cohort study in the United States (Health, Aging and Body Composition study). To measure adherence to a Mediterranean diet, we calculated race-specific tertiles of the MedDiet score (range: 0-55) using baseline food frequency questionnaires. Cognitive decline was assessed using repeated Modified Mini Mental State Examination scores over the study. We used linear mixed models to assess the association between MedDiet score and trajectory of cognitive decline. Results. Among blacks, participants with high MedDiet scores had a significantly lower mean rate of decline on the Modified Mini Mental State Examination score compared with participants with lower MedDiet scores (middle and bottom tertiles). The mean difference in points per year was 0.22 (95% confidence interval: 0.05-0.39; p = .01) after adjustment for age, sex, education, body mass index, current smoking, physical activity, depression, diabetes, total energy intake, and socioeconomic status. No association between MedDiet scores and change in Modified Mini Mental State Examination score was seen among white participants (p = .14). Conclusions. Stronger adherence to the Mediterranean diet may reduce the rate of cognitive decline among black, but not white older adults. Further studies in diverse populations are needed to confirm this association and pinpoint mechanisms that may explain these results. C1 [Koyama, Alain] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Koyama, Alain; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Houston, Denise K.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Lee, Jung Sun] Univ Georgia, Athens, GA 30602 USA. [Ayonayon, Hilsa N.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shahar, Danit R.] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Epidemiol & Hlth Evaluat, S Daniel Int Ctr Hlth & Nutr, IL-84105 Beer Sheva, Israel. [Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Koyama, A (reprint author), San Francisco VA Med Ctr, 4150 Clement St,VAMC 116H, San Francisco, CA 94121 USA. EM akk412@mail.harvard.edu OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU National Institute of Aging [K24 AG 031155, R01 AG 026720]; Alzheimer's Association [IIRG-08-88872]; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR [R01-NR012459]; Intramural Research Program of the NIH, National Institute on Aging FX Funded in part by grants K24 AG 031155 and R01 AG 026720 from the National Institute of Aging and grant IIRG-08-88872 from the Alzheimer's Association. This research was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106, NIA grant R01-AG028050, and NINR grant R01-NR012459. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 39 TC 4 Z9 4 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2015 VL 70 IS 3 BP 352 EP 357 DI 10.1093/gerona/glu097 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CC1RZ UT WOS:000350122200011 PM 24994847 ER PT J AU Chambers, KJ Kraft, S Emerick, K AF Chambers, Kyle J. Kraft, Stefan Emerick, Kevin TI Evaluation of Frozen Section Margins in High-Risk Cutaneous Squamous Cell Carcinomas of the Head and Neck SO LARYNGOSCOPE LA English DT Article DE Frozen section; high-risk cutaneous squamous cell carcinoma; perineural invasion ID SURGERY HISTOPATHOLOGY CONCORDANCE; PROGNOSTIC FACTORS; UNITED-STATES; SKIN; METASTASIS; MANAGEMENT AB Objectives/HypothesisTo identify histopathologic features associated with poor correlation of frozen and permanent pathology margins following wide local excision for advanced cutaneous squamous cell carcinomas of the head and neck. Study DesignRetrospective review. MethodsA retrospective review of patients undergoing excision of advanced head and neck squamous cell carcinomas between the years 2010 AND 2013 was performed. Demographic, operative, and pathology data were collected. Overall correlation between frozen section margins and final margins on permanent section results was calculated. Positive and negative predictive values of several histopathologic features were determined. ResultsForty-one cases were identified from the database. Perineural invasion, lymphovascular invasion, and a component of poorly differentiated carcinoma were identified in 61.3%, 34.5%, and 17.1% of cases, respectively. Discrepancy between frozen section margins and permanent margins was identified in eight cases (19.5%). The false-negative rate for poorly differentiated carcinoma, lymphovascular invasion, and perineural invasion was 14%, 36%, 26%, respectively. The positive and negative predictive value of poorly differentiated carcinoma, lymphovascular invasion, and perineural invasion in predicting discrepancy between frozen and permanent margins was 14% and 80%, 36% and 84%, and 26% and 92%, respectively. ConclusionsThis study demonstrated a moderate rate of discrepancy between frozen and permanent section analysis of operative margins from high-risk cutaneous squamous cell carcinomas of the head and neck. The presence or absence of certain histopathologic features appears to be associated with a higher rate of frozen section discrepancy. Evaluation of these features in a preoperative biopsy or staging excision may be useful in planning definitive excision and reconstruction. C1 [Chambers, Kyle J.; Emerick, Kevin] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Chambers, Kyle J.; Emerick, Kevin] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kraft, Stefan] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. RP Chambers, KJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM kyle_chambers@meei.harvard.edu NR 20 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 2015 VL 125 IS 3 BP 636 EP 639 DI 10.1002/lary.24945 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CB9PN UT WOS:000349964100030 PM 25230253 ER PT J AU Rosado, FG Oliveira, JL Sohani, AR Schroyens, W Sykes, DB Kenderian, SS Lacy, MQ Kyle, RA Hoyer, JD AF Rosado, Flavia G. Oliveira, Jennifer L. Sohani, Aliya R. Schroyens, Wilfried Sykes, David B. Kenderian, Saad S. Lacy, Martha Q. Kyle, Robert A. Hoyer, James D. TI Bone marrow findings of the newly described TEMPI syndrome: when erythrocytosis and plasma cell dyscrasia coexist SO MODERN PATHOLOGY LA English DT Article ID SCHNITZLER-SYNDROME; MONOCLONAL GAMMOPATHY; BORTEZOMIB AB TEMPI syndrome (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) is a recently described syndrome that, owing to erythrocytosis, may be confused with polycythemia vera. It is best classified as a type of plasma cell dyscrasia with paraneoplastic manifestations, similar to POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin abnormalities). To date, 11 patients have been identified. This is the first morphologic review of TEMPI syndrome bone marrow samples, in order to define pathologic features that may aid in the recognition of the syndrome and to identify post-therapy changes. Seven bone marrow aspirates and biopsies from three patients, including two post-treatment marrows, were examined. Patients were 36, 49, and 49 years old at time of diagnosis. In all cases, erythropoietin levels were extremely elevated at >5000 IU/I, the paraprotein was IgG kappa, JAK2 V617F was negative and vascular endothelial growth factor levels were normal. In one case, the increase in clonal plasma cells reached levels of smoldering myeloma (18%), but remaining marrows showed few monoclonal plasma cells (<5%). All pre-treatment biopsies showed erythroid hyperplasia, with mild nonspecific megakaryocytic, and erythroid cytologic atypia in one marrow. Prominent plasma cell vacuolization and reactive-appearing lymphoid aggregates were noted in one case. Findings of myeloproliferative neoplasms, including megakaryocyte clusters and fibrosis, were not identified. In conclusion, TEMPI syndrome should be considered when erythrocytosis and plasma cell dyscrasia coexist. The bone marrow findings, although nonspecific, differ significantly from polycythemia vera. Peculiar clinical and laboratorial findings of TEMPI, including elevated erythropoietin and normal vascular endothelial growth factor level, allow the diagnosis and distinction from POEMS syndrome. Significant decrease in erythropoietin level following treatment suggests a role of erythropoietin in monitoring therapeutic response. C1 [Rosado, Flavia G.; Oliveira, Jennifer L.; Kenderian, Saad S.; Lacy, Martha Q.; Kyle, Robert A.; Hoyer, James D.] Mayo Clin, Rochester, MN USA. [Sohani, Aliya R.; Sykes, David B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schroyens, Wilfried] Univ Antwerp, B-2020 Antwerp, Belgium. RP Rosado, FG (reprint author), W Virginia Univ, Dept Pathol, Robert C Byrd Hlth Sci Ctr, POB 9203, Morgantown, WV 26506 USA. EM flaviarosado21@gmail.com OI Kenderian, Saad/0000-0003-2767-3830 NR 18 TC 3 Z9 3 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 MAR PY 2015 VL 28 IS 3 BP 367 EP 372 DI 10.1038/modpathol.2014.117 PG 6 WC Pathology SC Pathology GA CC3QX UT WOS:000350265200005 PM 25216227 ER PT J AU Chen, W Xiong, S Li, J Li, XY Liu, Y Zou, CB Mallampalli, RK AF Chen, Wei Xiong, Sheng Li, Jin Li, Xiuying Liu, Yuan Zou, Chunbin Mallampalli, Rama K. TI The Ubiquitin E3 Ligase SCF-FBXO24 Recognizes Deacetylated Nucleoside Diphosphate Kinase A To Enhance Its Degradation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID F-BOX PROTEINS; METASTATIC SUPPRESSOR NM23-H1; TUMOR-METASTASIS; PROTEASOMAL DEGRADATION; SUBSTRATE RECOGNITION; DEPENDENT REGULATION; CELL-PROLIFERATION; STRUCTURAL BASIS; COMPLEX; BINDING AB The Skp-Cul-F box (SCF) ubiquitin E3 ligase machinery recognizes predominantly phosphodegrons or, less commonly, an (I/L) Q molecular signature within substrates to facilitate their recruitment in mediating protein ubiquitination and degradation. Here, we examined the molecular signals that determine the turnover of the multifunctional enzyme nucleoside diphosphate kinase A (NDPK-A) that controls cell proliferation. NDPK-A protein exhibits a half-life of similar to 6 h in HeLa cells and is targeted for ubiquitylation through actions of the F-box protein FBXO24. SCF-FBXO24 polyubiquitinates NDPK-A at K85, and two NH2-terminal residues, L55 and K56, were identified as important molecular sites for FBXO24 interaction. Importantly, K56 acetylation impairs its interaction with FBXO24, and replacing K56 with Q56, an acetylation mimic, reduces NDPK-A FBXO24 binding capacity. The acetyltransferase GCN5 catalyzes K56 acetylation within NDPK-A, thereby stabilizing NDPK-A, whereas GCN5 depletion in cells accelerates NDPK-A degradation. Cellular expression of an NDPK-A acetylation mimic or FBXO24 silencing increases NDPK-A life span which, in turn, impairs cell migration and wound healing. We propose that lysine acetylation when presented in the appropriate context may be recognized by some F-box proteins as a unique inhibitory molecular signal for their recruitment to restrict substrate degradation. C1 [Chen, Wei; Xiong, Sheng; Li, Xiuying] Jinan Univ, Coll Life Sci & Technol, Inst Biomed, Guangzhou, Guangdong, Peoples R China. [Chen, Wei; Xiong, Sheng; Li, Xiuying] Jinan Univ, Coll Life Sci & Technol, Natl Engn Res Ctr Genet Med, Guangzhou, Guangdong, Peoples R China. [Li, Jin; Liu, Yuan; Zou, Chunbin; Mallampalli, Rama K.] Univ Pittsburgh, Acute Lung Injury Ctr Excellence, Dept Med, Pittsburgh, PA 15260 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zou, CB (reprint author), Univ Pittsburgh, Acute Lung Injury Ctr Excellence, Dept Med, Pittsburgh, PA 15260 USA. EM zouc@upmc.edu; mallampallirk@upmc.edu FU National Institutes of Health R01 [HL096376, HL097376, HL098174, HL081784, 1UH2HL123502, P01 HL114453]; American Heart Association Award [12SDG12040330]; U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; U.S. Department of Veterans Affairs; National Project for Significant New Drugs Development of the MOST of China [2012ZX09103-301-033, 2012ZX09202-301-001]; Natural Science Foundation of China [30873082]; Major Biotech Industrialization Projects from the Guangzhou Municipal Science and Technology Bureau [2010U1-E00541] FX This work was supported, in part, by National Institutes of Health R01 grants HL096376, HL097376, HL098174, HL081784, 1UH2HL123502, P01 HL114453 (to R.K.M.) and American Heart Association Award 12SDG12040330 (to C.Z.). This work was also supported in part by the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, and a Merit Review Award from the U.S. Department of Veterans Affairs. This work was also supported, in part, by grants from the National Project for Significant New Drugs Development of the MOST of China (2012ZX09103-301-033 and 2012ZX09202-301-001), the Natural Science Foundation of China (30873082), and the Major Biotech Industrialization Projects from the Guangzhou Municipal Science and Technology Bureau (2010U1-E00541) to W.C., S.X., and X.L. NR 46 TC 1 Z9 2 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2015 VL 35 IS 6 BP 1001 EP 1013 DI 10.1128/MCB.01185-14 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CB9KS UT WOS:000349951100007 PM 25582197 ER PT J AU Patel, MS Wright, AJ Kohn, R Markmann, JF Kotton, CN Vagefi, PA AF Patel, Madhukar S. Wright, Alissa J. Kohn, Rachel Markmann, James F. Kotton, Camille N. Vagefi, Parsia A. TI Successful long-term management of invasive cerebral fungal infection following liver transplantation SO MYCOSES LA English DT Article DE Liver transplantation; fungal infection ID BOYDII BRAIN-ABSCESS; CLINICAL-PRACTICE; ASPERGILLOSIS; VORICONAZOLE; RECIPIENTS; SCEDOSPORIUM; POSACONAZOLE; GUIDELINES; SURVIVAL; THERAPY AB Central nervous system (CNS) infections after liver transplantation may be fungal in aetiology, with involvement from either common organisms such as Cryptococcus neoformans and Aspergillus spp. as well as less common organisms, such as the Mucorales and Scedosporium spp. Although the mortality of CNS fungal infections was nearly 100% in early series, more recent data has suggested that good outcomes can be achieved. This may be due to both improved diagnostic capabilities, such as the ability to obtain fungal susceptibilities and therapeutic drug levels, and improved therapeutic options, such as the newer triazoles- voriconazole and posaconazole. Due to improved outcomes, issues have now arisen around the long-term tolerability of these agents. The following two cases of invasive cerebral fungal infections following liver transplantation, one with Aspergillus flavus, and the other with Scedosporium boydii/apiospermum highlight the success that can be seen with the modern management of a previously fatal diagnosis. In particular, we highlight the issues around therapeutic monitoring and discontinuation of therapy. C1 [Patel, Madhukar S.; Markmann, James F.; Vagefi, Parsia A.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wright, Alissa J.] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Kohn, Rachel] Hosp Univ Penn, Dept Pulm & Crit Care Med, Philadelphia, PA 19104 USA. [Kotton, Camille N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White 544b, Boston, MA 02114 USA. EM pvagefi@mgh.harvard.edu NR 23 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAR PY 2015 VL 58 IS 3 BP 181 EP 186 DI 10.1111/myc.12289 PG 6 WC Dermatology; Mycology SC Dermatology; Mycology GA CB9KZ UT WOS:000349951800009 PM 25590987 ER PT J AU Lewis, HD Liddle, J Coote, JE Atkinson, SJ Barker, MD Bax, BD Bicker, KL Bingham, RP Campbell, M Chen, YH Chung, CW Craggs, PD Davis, RP Eberhard, D Joberty, G Lind, KE Locke, K Maller, C Martinod, K Patten, C Polyakova, O Rise, CE Rudiger, M Sheppard, RJ Slade, DJ Thomas, P Thorpe, J Yao, G Drewes, G Wagner, DD Thompson, PR Prinjha, RK Wilson, DM AF Lewis, Huw D. Liddle, John Coote, Jim E. Atkinson, Stephen J. Barker, Michael D. Bax, Benjamin D. Bicker, Kevin L. Bingham, Ryan P. Campbell, Matthew Chen, Yu Hua Chung, Chun-Wa Craggs, Peter D. Davis, Rob P. Eberhard, Dirk Joberty, Gerard Lind, Kenneth E. Locke, Kelly Maller, Claire Martinod, Kimberly Patten, Chris Polyakova, Oxana Rise, Cecil E. Ruediger, Martin Sheppard, Robert J. Slade, Daniel J. Thomas, Pamela Thorpe, Jim Yao, Gang Drewes, Gerard Wagner, Denisa D. Thompson, Paul R. Prinjha, Rab K. Wilson, David M. TI Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation SO NATURE CHEMICAL BIOLOGY LA English DT Article ID NEUTROPHIL EXTRACELLULAR TRAPS; ARGININE DEIMINASE 4; GENE-EXPRESSION; TARGET; REFINEMENT; ACTIVATION; SIMILARITY; THROMBOSIS; DESIGN AB PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation for, to our knowledge, the first time. The therapeutic potential of PAD4 inhibitors can now be explored. C1 [Lewis, Huw D.; Liddle, John; Atkinson, Stephen J.; Barker, Michael D.; Campbell, Matthew; Davis, Rob P.; Maller, Claire; Patten, Chris; Sheppard, Robert J.; Prinjha, Rab K.; Wilson, David M.] GlaxoSmithKline, Med Res Ctr, Immunoinflammat Therapy Area, EpiNova DPU, Stevenage, Herts, England. [Coote, Jim E.; Bax, Benjamin D.; Bingham, Ryan P.; Chen, Yu Hua; Chung, Chun-Wa; Craggs, Peter D.; Locke, Kelly; Polyakova, Oxana; Ruediger, Martin; Thomas, Pamela; Thorpe, Jim] GlaxoSmithKline, Med Res Ctr, Stevenage, Herts, England. [Bicker, Kevin L.; Slade, Daniel J.; Thompson, Paul R.] Scripps Florida, Scripps Res Inst, Dept Chem, Jupiter, FL USA. [Eberhard, Dirk; Joberty, Gerard; Drewes, Gerard] A GSK Co, Cellzome GmbH, Heidelberg, Germany. [Lind, Kenneth E.; Rise, Cecil E.; Yao, Gang] GlaxoSmithKline, ELT Boston Platform Technol & Sci, Waltham, MA USA. [Martinod, Kimberly; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Martinod, Kimberly] Harvard Univ, Sch Med, Div Med Sci, Grad Program Immunol, Boston, MA 02115 USA. [Wagner, Denisa D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lewis, HD (reprint author), GlaxoSmithKline, Med Res Ctr, Immunoinflammat Therapy Area, EpiNova DPU, Stevenage, Herts, England. EM huw.d.lewis@gsk.com OI Martinod, Kimberly/0000-0002-1026-6107; Slade, Daniel/0000-0001-5634-7220 FU US National Institutes of Health [GM079357, R01 HL102101] FX This work was supported in part by US National Institutes of Health grants GM079357 (to P. R. T.) and R01 HL102101 (to D. D. W.). We thank the following colleagues for their medicinal and synthetic chemistry contributions to this manuscript: D. Amans, H. Diallo, C. Douault, N. Garton, K. Jones, J. Renaux, T. Shipley, A. Walker, B. Watson and C. Wellaway. We also gratefully acknowledge S. Ready for diligently preparing and quantifying S. aureus for neutrophil studies. For the chemoproteomics data, we would like to thank M. Boesche and Cellzome's tissue culture and target validation teams for technical expertise and M. Bantscheff for stimulating discussion. We thank M. Neu and P. Homes for assistance for structural studies and B. Nolte for advice on crystallography. NR 35 TC 47 Z9 47 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD MAR PY 2015 VL 11 IS 3 BP 189 EP + DI 10.1038/nchembio.1735 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CB7WY UT WOS:000349840500006 PM 25622091 ER PT J AU Sankaran, VG Weiss, MJ AF Sankaran, Vijay G. Weiss, Mitchell J. TI Anemia: progress in molecular mechanisms and therapies SO NATURE MEDICINE LA English DT Review ID SICKLE-CELL-DISEASE; DIAMOND-BLACKFAN ANEMIA; FETAL-HEMOGLOBIN EXPRESSION; HEMATOPOIETIC STEM-CELLS; BETA-THALASSEMIC MICE; CONGENITAL ERYTHROPOIETIC PORPHYRIA; GENOME-WIDE ASSOCIATION; CHRONIC KIDNEY-DISEASE; ZINC-FINGER NUCLEASES; FACTOR KLF1 CAUSES AB Anemia is a major source of morbidity and mortality worldwide. Here we review recent insights into how red blood cells (RBCs) are produced, the pathogenic mechanisms underlying various forms of anemia, and novel therapies derived from these findings. It is likely that these new insights, mainly arising from basic scientific studies, will contribute immensely to both the understanding of frequently debilitating forms of anemia and the ability to treat affected patients. Major worldwide diseases that are likely to benefit from new advances include the hemoglobinopathies (beta-thalassemia and sickle cell disease); rare genetic disorders of RBC production; and anemias associated with chronic kidney disease, inflammation, and cancer. Promising new approaches to treatment include drugs that target recently defined pathways in RBC production, iron metabolism, and fetal globin-family gene expression, as well as gene therapies that use improved viral vectors and newly developed genome editing technologies. C1 [Sankaran, Vijay G.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Hematol & Oncol, Boston, MA 02115 USA. [Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sankaran, Vijay G.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Weiss, Mitchell J.] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA. RP Sankaran, VG (reprint author), Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Hematol & Oncol, Boston, MA 02115 USA. EM sankaran@broadinstitute.org; mitch.weiss@stjude.org FU US National Institutes of Health (NIH) [R01 DK103794, R21 HL120791, U01 HL117720]; March of Dimes Basil O'Connor Scholar Award; Diamond-Blackfan Anemia Foundation; NIH [R01 DK0923128, R01 DK61692, R01 HL088554] FX We apologize for being unable to cite numerous papers and studies in this field due to space limitations. We are grateful to N. Mohandas, A. Nienhuis, and D. Nathan for comments and suggestions on this Review. V.G.S. received support from the US National Institutes of Health (NIH; R01 DK103794, R21 HL120791, U01 HL117720), a March of Dimes Basil O'Connor Scholar Award and an award from the Diamond-Blackfan Anemia Foundation. M.J.W. received support from the NIH (R01 DK0923128, R01 DK61692, R01 HL088554). We are grateful to the many patients with anemia and their families, who have advanced the field by participating in clinical studies and advocating research. NR 119 TC 45 Z9 47 U1 19 U2 65 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 MAR PY 2015 VL 21 IS 3 BP 221 EP 230 DI 10.1038/nm.3814 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CC4YG UT WOS:000350362000014 PM 25742458 ER PT J AU Staley, K AF Staley, Kevin TI Molecular mechanisms of epilepsy SO NATURE NEUROSCIENCE LA English DT Review ID TEMPORAL-LOBE EPILEPSY; CA1 HIPPOCAMPAL REGION; SYNAPTIC-TRANSMISSION; STATUS EPILEPTICUS; MOUSE MODEL; POSTTRAUMATIC EPILEPSY; SEIZURE FREQUENCY; ENTORHINAL CORTEX; GABA(A) RECEPTORS; DRAVET SYNDROME AB Decades of experimental work have established an imbalance of excitation and inhibition as the leading mechanism of the transition from normal brain function to seizure. In epilepsy, these transitions are rare and abrupt. Transition processes incorporating positive feedback, such as activity-dependent disinhibition, could provide these uncommon timing features. A rapidly expanding array of genetic etiologies will help delineate the molecular mechanism(s). This delineation will entail quite a bit of cell biology. The genes discovered so far are more remarkable for their diversity than their similarities. C1 [Staley, Kevin] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Staley, Kevin] Harvard Univ, Sch Med, Boston, MA USA. RP Staley, K (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM staley.kevin@mgh.harvard.edu FU US National Institutes of Health [NS034700, NS040109] FX This work was funded by US National Institutes of Health grants NS034700 and NS040109. NR 82 TC 24 Z9 24 U1 178 U2 213 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAR PY 2015 VL 18 IS 3 BP 367 EP 372 DI 10.1038/nn.3947 PG 6 WC Neurosciences SC Neurosciences & Neurology GA CC2SO UT WOS:000350195100014 PM 25710839 ER PT J AU Keung, AJ Joung, JK Khalil, AS Collins, JJ AF Keung, Albert J. Joung, J. Keith Khalil, Ahmad S. Collins, James J. TI Chromatin regulation at the frontier of synthetic biology SO NATURE REVIEWS GENETICS LA English DT Review ID NUCLEOSOME POSITIONING SEQUENCES; TRANSCRIPTION FACTOR-BINDING; TARGETED DNA METHYLATION; GENOME-WIDE ANALYSIS; IN-VIVO; SACCHAROMYCES-CEREVISIAE; HISTONE MODIFICATIONS; GENE-REGULATION; BUDDING YEAST; HUMAN-CELLS AB As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including 'epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication. C1 [Keung, Albert J.; Khalil, Ahmad S.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Keung, Albert J.; Khalil, Ahmad S.] Boston Univ, Ctr Synthet Biol, Boston, MA 02215 USA. [Keung, Albert J.; Collins, James J.] MIT, Synthet Biol Ctr, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Keung, Albert J.; Collins, James J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Khalil, Ahmad S.; Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Collins, James J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Collins, JJ (reprint author), MIT, Synthet Biol Ctr, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jimjc@mit.edu FU US National Institutes of Health (NIH)-National Institute of General Medical Sciences (NIGMS); NIH; Defense Advanced Research Projects Agency grant; Department of Biomedical Engineering at Boston University; National Science Foundation; Wyss Institute for Biologically Inspired Engineering; Howard Hughes Medical Institute FX This work was supported by a US National Institutes of Health (NIH)-National Institute of General Medical Sciences (NIGMS) Ruth L. Kirschstein Postdoctoral Fellowship (A.J.K.), an NIH Director's Pioneer Award (J.K.J.), a Defense Advanced Research Projects Agency grant (J.K.J., A.S.K., and J.J.C.), start-up funds from the Department of Biomedical Engineering at Boston University (A.S.K.), a National Science Foundation CAREER Award (A.S.K.), a NIH R24 (J.J.C.), the Wyss Institute for Biologically Inspired Engineering (J.J.C.) and the Howard Hughes Medical Institute (J.J.C.). Owing to space limitations, the authors regret that many important publications were not able to be discussed in this Review. NR 130 TC 28 Z9 28 U1 9 U2 60 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 EI 1471-0064 J9 NAT REV GENET JI Nat. Rev. Genet. PD MAR PY 2015 VL 16 IS 3 BP 159 EP 171 DI 10.1038/nrg3900 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA CB8PR UT WOS:000349893500010 PM 25668787 ER PT J AU Barshop, K Staller, K Semler, J Kuo, B AF Barshop, K. Staller, K. Semler, J. Kuo, B. TI Duodenal rather than antral motility contractile parameters correlate with symptom severity in gastroparesis patients SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE duodenal; gastroparesis; motility; small bowel; symptoms; wireless motility capsule ID FUNCTIONAL DYSPEPSIA; ANTRODUODENAL MANOMETRY; PAGI-SYM; CAPSULE; DYSMOTILITY; HEALTHY; VALIDATION; DISORDERS; GCSI AB BackgroundStudies of symptomatic gastroparetics consistently find poor correlation with gastric emptying. We hypothesized that concomitant small bowel dysmotility may play a role in symptom causation in gastroparesis and sought to test this hypothesis by using wireless motility capsule (WMC) testing to simultaneously measure antral and duodenal area under pressure curve (AUC) in patients with delayed gastric emptying. MethodsUsing a cohort from a multicenter clinical trial and a separate tertiary clinical database, we identified gastroparetics that underwent concurrent WMC testing and completed the Gastroparesis Cardinal Symptom Index, a validated questionnaire. Our study included 35 gastroparetics defined by a gastric emptying time (GET) 5h. Antral and duodenal AUC were assessed at 1-h windows pre-GET and post-GET, respectively. Key ResultsWe found moderate correlations between duodenal AUC and symptom severity in the combined cohort (n=35; R=-0.42; p=0.01; 95% CI -0.7, -0.1). Removing patients with colonic delay resulted in a stronger correlation of duodenal AUC to symptom severity (n=21; R=-0.63; p<0.01; 95% CI -0.81, -0.31). The multicenter trial (n=20) and clinical practice cohorts (n=15) had significantly different symptom severity and exclusion criteria. When analyzed separately, significant correlations between duodenal AUC and symptom severity were observed (R=-0.71; p<0.01; 95% CI -0.9, -0.4 and R=-0.72; p<0.01; 95% CI -0.9, -0.3, respectively). Symptom severity and antral motility showed no correlation. Conclusions & InferencesWe found significant correlations between duodenal AUC and symptom severity in two cohorts of gastroparetics. Small bowel motility may contribute to symptom generation in gastroparetic patients and this may inform therapeutic considerations. C1 [Barshop, K.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Staller, K.; Kuo, B.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM braden.kuo@gmail.com OI Staller, Kyle/0000-0003-4925-4290 FU SmartPill Corporation; NYSTAR [C020118]; NIH [DK069614]; International Foundation for Functional GI Disorders FX The trial was sponsored by The SmartPill Corporation and partly supported by NYSTAR grant C020118, NIH grant DK069614, and the International Foundation for Functional GI Disorders. NR 24 TC 4 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAR PY 2015 VL 27 IS 3 BP 339 EP 346 DI 10.1111/nmo.12496 PG 8 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA CC2CV UT WOS:000350153400005 PM 25521513 ER PT J AU Wu, RH Xiao, G Zhou, IY Ran, CZ Sun, PZ AF Wu, Renhua Xiao, Gang Zhou, Iris Yuwen Ran, Chongzhao Sun, Phillip Zhe TI Quantitative chemical exchange saturation transfer (qCEST) MRI - omega plot analysis of RF-spillover-corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate SO NMR IN BIOMEDICINE LA English DT Article DE chemical exchange saturation transfer (CEST); omega plot; quantitative CEST (qCEST) analysis ID ACUTE CEREBRAL-ISCHEMIA; MAGNETIZATION-TRANSFER; 7 T; HUMAN BRAIN; PH; AGENTS; TIME AB Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST-weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH-dependent exchange rate followed a dominantly base-catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Wu, Renhua; Xiao, Gang] Shantou Univ, Affiliated Hosp 2, Dept Radiol, Coll Med, Shantou, Peoples R China. [Xiao, Gang] Hanshan Normal Univ, Dept Math & Stat, Chaozhou, Peoples R China. [Zhou, Iris Yuwen; Ran, Chongzhao; Sun, Phillip Zhe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Zhou, Iris Yuwen; Ran, Chongzhao; Sun, Phillip Zhe] Harvard Univ, Sch Med, Charlestown, MA USA. RP Sun, PZ (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu RI Zhou, Iris Yuwen/A-2089-2017 OI Zhou, Iris Yuwen/0000-0002-4351-7398 FU NSFC [30930027]; NIH/NIBIB [K01EB009771]; NIH/NINDS [1R01NS083654] FX This study was supported in part by grants from NSFC 30930027, NIH/NIBIB K01EB009771 and NIH/NINDS 1R01NS083654. This work has been presented at the ISMRM-ESMRMB Joint Annual Meeting, Milan, 2014. NR 54 TC 6 Z9 7 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD MAR PY 2015 VL 28 IS 3 BP 376 EP 383 DI 10.1002/nbm.3257 PG 8 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA CC1XX UT WOS:000350139800011 PM 25615718 ER PT J AU del Carmen, MG Rice, LW AF del Carmen, Marcela G. Rice, Laurel W. TI Underrepresentation of Women in Clinical Trials Why Gynecologic Oncologists Are Worried SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CISPLATIN; HEALTH; SEX; CARCINOMA; RADIATION; THERAPY; DISEASE; CANCER AB In gynecologic oncology, significant advances with improved patient outcomes have clearly and thankfully resulted from randomized clinical trials. The recent restructuring of cooperative groups and decreased funding for phase III clinical trials have unintentionally resulted in a 90% reduction of available trials and accrual in gynecologic oncology. This Commentary reviews the history of the underrepresentation of women in clinical trials, highlighting the challenges that threaten the viability of gynecologic oncology clinical research, resulting in a decreased likelihood of improving the survival of women with gynecologic cancer. We suggest an opportunity for partnering with the U.S. government and the private sector to enhance research funding opportunities while increasing advocacy efforts to reinvigorate our clinical trials platform. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. Univ Wisconsin Hosp & Clin, Dept Obstet & Gynecol, Madison, WI 53792 USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 22 TC 3 Z9 3 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2015 VL 125 IS 3 BP 616 EP 619 DI 10.1097/AOG.0000000000000695 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CC1QY UT WOS:000350118100014 PM 25730224 ER PT J AU Barth, WH AF Barth, William H., Jr. TI Persistent Occiput Posterior SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FETAL HEAD POSITION; OPERATIVE VAGINAL DELIVERY; TRANSVAGINAL DIGITAL EXAMINATION; TRANSABDOMINAL ULTRASOUND ASSESSMENT; RANDOMIZED CONTROLLED-TRIAL; ANAL-SPHINCTER INJURY; CESAREAN DELIVERY; NEONATAL MORBIDITY; OCCIPITOPOSTERIOR POSITION; INTRAPARTUM SONOGRAPHY AB Persistent occiput posterior (OP) is associated with increased rates of maternal and newborn morbidity. Its diagnosis by physical examination is challenging but is improved with bedside ultrasonography. Occiput posterior discovered in the active phase or early second stage of labor usually resolves spontaneously. When it does not, prophylactic manual rotation may decrease persistent OP and its associated complications. When delivery is indicated for arrest of descent in the setting of persistent OP, a pragmatic approach is suggested. Suspected fetal macrosomia, a biparietal diameter above the pelvic inlet or a maternal pelvis with android features should prompt cesarean delivery. Nonrotational operative vaginal delivery is appropriate when the maternal pelvis has a narrow anterior segment but ample room posteriorly, like with anthropoid features. When all other conditions are met and the fetal head arrests in an OP position in a patient with gynecoid pelvic features and ample room anteriorly, options include cesarean delivery, nonrotational operative vaginal delivery, and rotational procedures, either manual or with the use of rotational forceps. Recent literature suggests that maternal and fetal outcomes with rotational forceps are better than those reported in older series. Although not without significant challenges, a role remains for teaching and practicing selected rotational forceps operations in contemporary obstetrics. C1 [Barth, William H., Jr.] Harvard Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Barth, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Massachusetts Gen Hosp Founders 418, Div Maternal Fetal Med,Dept Obstet & Gynecol,Med, 55 Fruit St, Boston, MA 02114 USA. EM wbarthjr@mgh.harvard.edu NR 91 TC 10 Z9 11 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2015 VL 125 IS 3 BP 695 EP 709 DI 10.1097/AOG.0000000000000647 PG 15 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CC1QY UT WOS:000350118100025 PM 25730235 ER PT J AU Remenschneider, A Santos, F AF Remenschneider, Aaron Santos, Felipe TI PNEUMOCEPHALUS, HEARING LOSS, AND VERTIGO AFTER AIRLINE FLIGHT IN A PATIENT WITH SUPERIOR CANAL DEHISCENCE Reply SO OTOLOGY & NEUROTOLOGY LA English DT Letter C1 [Remenschneider, Aaron; Santos, Felipe] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Remenschneider, A (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. EM aaron_remenschneider@meei.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAR PY 2015 VL 36 IS 3 BP 561 EP 562 PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA CB6XI UT WOS:000349769700039 PM 25823355 ER PT J AU Chong, CR Linnoila, I Janne, PA Johnson, BE Sholl, LM AF Chong, Curtis R. Linnoila, Ilona Jaenne, Pasi A. Johnson, Bruce E. Sholl, Lynette M. TI Pathologic Classification of Pulmonary Carcinoid Cell Lines SO PANCREAS LA English DT Meeting Abstract C1 [Chong, Curtis R.; Jaenne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Linnoila, Ilona] NCI, Bethesda, MD 20892 USA. [Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD MAR PY 2015 VL 44 IS 2 BP 347 EP 347 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CB6XF UT WOS:000349769400030 ER PT J AU Chong, CR Johnson, BE Janne, PA AF Chong, Curtis R. Johnson, Bruce E. Jaenne, Pasi A. TI Drug Discovery for Atypical Pulmonary Carcinoid Using a Library of Targeted Agents SO PANCREAS LA English DT Meeting Abstract C1 [Chong, Curtis R.; Johnson, Bruce E.; Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD MAR PY 2015 VL 44 IS 2 BP 347 EP 347 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CB6XF UT WOS:000349769400029 ER PT J AU Chong, CR Wirth, LJ Nishino, M Chen, AB Sholl, L McNamee, CJ Janne, PA Johnson, BE AF Chong, Curtis R. Wirth, Lori J. Nishino, Mizuki Chen, Aileen B. Sholl, LynetteM. McNamee, Ciaran J. Jaenne, Pasi A. Johnson, Bruce E. TI Chemotherapy for Locally Advanced and Metastatic Pulmonary Carcinoid Tumors SO PANCREAS LA English DT Meeting Abstract C1 [Chong, Curtis R.; Nishino, Mizuki; Chen, Aileen B.; Sholl, LynetteM.; McNamee, Ciaran J.; Jaenne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wirth, Lori J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD MAR PY 2015 VL 44 IS 2 BP 352 EP 352 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CB6XF UT WOS:000349769400046 ER PT J AU Phan, AT Halperin, DM Chan, JA Fogelman, DR Hess, KR Malinowski, P Regan, E Ng, CS Yao, JC Kulke, MH AF Phan, Alexandria T. Halperin, Daniel M. Chan, Jennifer A. Fogelman, David R. Hess, Kenneth R. Malinowski, Paige Regan, Eileen Ng, Chaan S. Yao, James C. Kulke, Matthew H. TI A Prospective, Multi-Institutional Phase II Study of Pazopanib and Depot Octreotide in Advanced, Well-Differentiated Neuroendocrine Tumors SO PANCREAS LA English DT Meeting Abstract C1 [Phan, Alexandria T.; Halperin, Daniel M.; Fogelman, David R.; Yao, James C.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Chan, Jennifer A.; Malinowski, Paige; Regan, Eileen; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hess, Kenneth R.; Ng, Chaan S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 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 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD MAR PY 2015 VL 44 IS 2 BP 356 EP 356 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CB6XF UT WOS:000349769400058 ER PT J AU Qian, ZR Francis, JM Ter-Minassian, M Chan, JA Brais, LK Hooshmand, SM Brooks, N Nishihara, R Li, TT Imamura, Y Yamauchi, M Inamura, K Kim, SA Mima, K Sukawa, Y Masuda, A Yang, JH Lin, XH Christiani, DC Fuchs, CS Meyerson, M Ogino, S Kulke, MH AF Qian, Zhi Rong Francis, Joshua M. Ter-Minassian, Monica Chan, Jennifer A. Brais, Lauren K. Hooshmand, Susanne M. Brooks, Nichole Nishihara, Reiko Li, Tingting Imamura, Yu Yamauchi, Mai Inamura, Kentaro Kim, Sun A. Mima, Kosuke Sukawa, Yasutaka Masuda, Atsuhiro Yang, Juhong Lin, Xihong Christiani, David C. Fuchs, Charles S. Meyerson, Matthew Ogino, Shuji Kulke, Matthew H. TI Prognostic Significance of CDKN1B (p27) Expression in Gastroenteropancreatic Neuroendocrine Tumors SO PANCREAS LA English DT Meeting Abstract C1 [Qian, Zhi Rong; Francis, Joshua M.; Ter-Minassian, Monica; Chan, Jennifer A.; Brais, Lauren K.; Hooshmand, Susanne M.; Brooks, Nichole; Nishihara, Reiko; Li, Tingting; Imamura, Yu; Yamauchi, Mai; Inamura, Kentaro; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Masuda, Atsuhiro; Yang, Juhong; Fuchs, Charles S.; Meyerson, Matthew; Ogino, Shuji; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Qian, Zhi Rong; Francis, Joshua M.; Ter-Minassian, Monica; Chan, Jennifer A.; Brais, Lauren K.; Hooshmand, Susanne M.; Brooks, Nichole; Nishihara, Reiko; Li, Tingting; Imamura, Yu; Yamauchi, Mai; Inamura, Kentaro; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Masuda, Atsuhiro; Yang, Juhong; Fuchs, Charles S.; Meyerson, Matthew; Ogino, Shuji; Kulke, Matthew H.] Harvard Univ, Sch Med, Boston, MA USA. [Francis, Joshua M.; Christiani, David C.; Meyerson, Matthew] Broad Inst, Cambridge, MA USA. [Ter-Minassian, Monica] Chinese Peoples Liberat Army Gen Hosp, Dept Environm Hlth, Beijing 100853, Peoples R China. [Li, Tingting] Chinese Peoples Liberat Army Gen Hosp, Dept Geriatr Gastroenterol, Beijing 100853, Peoples R China. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Christiani, David C.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fuchs, Charles S.] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD MAR PY 2015 VL 44 IS 2 BP 356 EP 356 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CB6XF UT WOS:000349769400059 ER PT J AU Wheeler, D Kulke, M O'Dorisio, T Horsch, D Jackson, S Ye, GL Kim, HW Zambrowicz, B Sands, AA Fleming, D AF Wheeler, Darren Kulke, Matthew O'Dorisio, Thomas Hoersch, Dieter Jackson, Shanna Ye, Gui-Lan Kim, Hyung-Woo Zambrowicz, Brian Sands, Arthur A. Fleming, Douglas TI Telotristat Etiprate (TE) in a Subset of Patients With Carcinoid Heart Disease Included in Two Phase 2 Trials for Carcinoid Syndrome SO PANCREAS LA English DT Meeting Abstract C1 [Wheeler, Darren; Jackson, Shanna; Ye, Gui-Lan; Kim, Hyung-Woo; Zambrowicz, Brian; Sands, Arthur A.; Fleming, Douglas] Lexicon Pharmaceut Inc, The Woodlands, TX USA. [Kulke, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Dorisio, Thomas] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Hoersch, Dieter] Zentralink Bad Berka GmbH, Bad Berka, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD MAR PY 2015 VL 44 IS 2 BP 361 EP 361 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CB6XF UT WOS:000349769400075 ER PT J AU Rice, MB Rifas-Shiman, SL Oken, E Gillman, MW Ljungman, PL Litonjua, AA Schwartz, J Coull, BA Zanobetti, A Koutrakis, P Melly, SJ Mittleman, MA Gold, DR AF Rice, Mary B. Rifas-Shiman, Sheryl L. Oken, Emily Gillman, Matthew W. Ljungman, Petter L. Litonjua, Augusto A. Schwartz, Joel Coull, Brent A. Zanobetti, Antonella Koutrakis, Petros Melly, Steven J. Mittleman, Murray A. Gold, Diane R. TI Exposure to Traffic and Early Life Respiratory Infection: A Cohort Study SO PEDIATRIC PULMONOLOGY LA English DT Article DE epidemiology; environmental lung disease; air pollution; traffic; prenatal exposures; respiratory infection ID AIR-POLLUTION; INFANT-MORTALITY; INCREASED SUSCEPTIBILITY; MYOCARDIAL-INFARCTION; SMOKE EXPOSURE; LUNG-FUNCTION; BIRTH-WEIGHT; CHILDREN; BRONCHIOLITIS; METAANALYSIS AB We examined whether proximity to a major roadway and traffic density around the home during pregnancy are associated with risk of early life respiratory infection in a pre-birth cohort in the Boston area. We geocoded addresses for 1,263 mother-child pairs enrolled during the first trimester of pregnancy in Project Viva during 1999-2002. We calculated distance from home to nearest major roadway and traffic density in a 100m buffer around the home. We defined respiratory infection as maternal report of 1 doctor-diagnosed pneumonia, bronchiolitis, croup, or other respiratory infection from birth until the early childhood visit (median age 3.3). We used relative risk regression models adjusting for potential confounders to estimate associations between traffic exposures and risk of respiratory infection. Distance to roadway during pregnancy was associated with risk of respiratory infection. In fully adjusted models, relative risks (95% CI) for respiratory infection were: 1.30 (1.08, 1.55) for <100m, 1.15 (0.93, 1.41) for 100 to <200m, and 0.95 (0.84, 1.07) for 200 to <1,000m compared with living 1,000m away from a major roadway. Each interquartile range increase in distance to roadway was associated with an 8% (95% CI 0.87, 0.98) lower risk, and each interquartile range increase in traffic density was associated with a 5% (95% CI 0.98, 1.13) higher risk of respiratory infection. Our findings suggest that living close to a major roadway during pregnancy may predispose the developing lung to infection in early life. Pediatr Pulmonol. 2015; 50:252-259. (c) 2014 Wiley Periodicals, Inc. C1 [Rice, Mary B.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Rice, Mary B.; Ljungman, Petter L.; Mittleman, Murray A.] Beth Israel Deaconess Med Ctr, Dept Med, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Rifas-Shiman, Sheryl L.; Oken, Emily; Gillman, Matthew W.] Harvard Univ, Sch Med, Obes Prevent Program, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Litonjua, Augusto A.; Gold, Diane R.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Schwartz, Joel; Coull, Brent A.; Zanobetti, Antonella; Koutrakis, Petros; Melly, Steven J.; Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Rice, MB (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM mrice2@partners.org RI Ljungman, Petter/C-6371-2014 OI Ljungman, Petter/0000-0002-7815-2632 FU NIH/NHLBI [5T32HL007374]; NIH/NIEHS [1F32ES023352-01, P30ES000002, P01-ES009825]; NIH/NIAID [R01AI102960]; NIH/NICHD [K24 HD069408]; US EPA [R832416, RD834798] FX NIH/NHLBI; Number: 5T32HL007374, NIH/NIEHS; Numbers: 1F32ES023352-01, P30ES000002, P01-ES009825, NIH/NIAID; Number: R01AI102960, NIH/NICHD; Number: K24 HD069408, US EPA; Numbers: R832416, RD834798. NR 33 TC 5 Z9 5 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD MAR PY 2015 VL 50 IS 3 BP 252 EP 259 DI 10.1002/ppul.23029 PG 8 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA CC0AS UT WOS:000349997700007 ER PT J AU Tiddens, HAWM Puderbach, M Venegas, JG Ratjen, F Donaldson, SH Davis, SD Rowe, SM Sagel, SD Higgins, M Waltz, DA AF Tiddens, Harm A. W. M. Puderbach, Michael Venegas, Jose G. Ratjen, Felix Donaldson, Scott H. Davis, Stephanie D. Rowe, Steven M. Sagel, Scott D. Higgins, Mark Waltz, David A. TI Novel Outcome Measures for Clinical Trials in Cystic Fibrosis SO PEDIATRIC PULMONOLOGY LA English DT Review DE cystic fibrosis; endpoints; outcome measures; imaging; sputum biomarkers; CFTR activity ID LUNG CLEARANCE INDEX; TRANSMEMBRANE CONDUCTANCE REGULATOR; POTENTIAL DIFFERENCE MEASUREMENTS; POSITRON-EMISSION-TOMOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; MULTIPLE-BREATH WASHOUT; INTESTINAL CURRENT MEASUREMENT; CHEST COMPUTED-TOMOGRAPHY; INHALED HYPERTONIC SALINE; NATIVE HUMAN COLON AB Cystic fibrosis (CF) is a common inherited condition caused by mutations in the gene encoding the CF transmembrane regulator protein. With increased understanding of the molecular mechanisms underlying CF and the development of new therapies there comes the need to develop new outcome measures to assess the disease, its progression and response to treatment. As there are limitations to the current endpoints accepted for regulatory purposes, a workshop to discuss novel endpoints for clinical trials in CF was held in Anaheim, California in November 2011. The pros and cons of novel outcome measures with potential utility for evaluation of novel treatments in CF were critically evaluated. The highlights of the 2011 workshop and subsequent advances in technologies and techniques that could be used to inform the development of clinical trial endpoints are summarized in this review. Pediatr Pulmonol. (c) 2014 The Authors. Pediatric Pulmonology published by Wiley Periodicals, Inc. C1 [Tiddens, Harm A. W. M.] Erasmus Univ, Med Ctr, Sophia Childrens Hosp, Dept Pediat Pulmonol & Allergol,Dept Radiol, NL-3000 CB Rotterdam, Netherlands. [Puderbach, Michael] Hufeland Klinikum, Dept Diagnost & Intervent Radiol, Bad Langensalza, Germany. [Venegas, Jose G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Ratjen, Felix] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Resp Med, Toronto, ON M5G 1X8, Canada. [Donaldson, Scott H.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Davis, Stephanie D.] Indiana Univ Sch Med, James Whitcomb Riley Hosp Children, Dept Pediat, Indianapolis, IN 46202 USA. [Rowe, Steven M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Sagel, Scott D.] Univ Colorado, Sch Med, Dept Pediat, Childrens Hosp Colorado, Denver, CO USA. [Higgins, Mark] Vertex Pharmaceut Europe, Abingdon, Oxon, England. [Waltz, David A.] Vertex Pharmaceut, Boston, MA USA. RP Tiddens, HAWM (reprint author), Erasmus Univ, Med Ctr, Sophia Childrens Hosp, Dept Pediat Pulmonol & Allergol,Dept Radiol, POB 2060, NL-3000 CB Rotterdam, Netherlands. EM h.tiddens@erasmusmc.nl FU Novartis Pharma AG (Basel, Switzerland) FX Novartis Pharma AG (Basel, Switzerland). NR 149 TC 8 Z9 8 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD MAR PY 2015 VL 50 IS 3 BP 302 EP 315 DI 10.1002/ppul.23146 PG 14 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA CC0AS UT WOS:000349997700013 ER PT J AU Nienhuis, HH Gaykema, SBM Timmer-Bosscha, H Jalving, M Brouwers, AH Lub-de Hooge, MN van der Vegt, B Overmoyer, B de Vries, EGE Schroder, CP AF Nienhuis, H. H. Gaykema, S. B. M. Timmer-Bosscha, H. Jalving, M. Brouwers, A. H. Lub-de Hooge, M. N. van der Vegt, B. Overmoyer, B. de Vries, E. G. E. Schroder, C. P. TI Targeting breast cancer through its microenvironment: Current status of preclinical and clinical research in finding relevant targets SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Microenvironment; Breast cancer; Targeted therapy; Biomarkers; Metastasis; Metabolism ID ENDOTHELIAL GROWTH-FACTOR; BODY-MASS INDEX; TYROSINE KINASE INHIBITOR; MATRIX-METALLOPROTEINASE INHIBITORS; POSITRON-EMISSION-TOMOGRAPHY; TUMOR-ASSOCIATED MACROPHAGES; MAMMARY-GLAND DEVELOPMENT; EPITHELIAL-MESENCHYMAL TRANSITION; BEVACIZUMAB-CONTAINING THERAPY; ADJUVANT ENDOCRINE THERAPY AB It is increasingly evident that not only breast cancer cells, but also the tissue embedding these cells: the tumor microenvironment, plays an important role in tumor progression, metastasis formation and treatment sensitivity. This review focuses on the current knowledge of processes by which the microenvironment affects breast cancer, including formation of the metastatic niche, metabolic stimulation, stimulation of tumor cell migration, immune modulation, angiogenesis and matrix remodeling. The number of drugs targeting key factors in these processes is expanding, and the available clinical data is increasing. Therefore current strategies for intervention and prediction of treatment response are outlined. At present, targeting the formation of the metastatic niche and metabolic stimulation by the breast cancer microenvironment, are already showing clinical efficacy. Intervening in the stimulation of tumor cell migration and immune modulation by the microenvironment upcoming fields of great research interest. In contrast, targeting microenvironmental angiogenesis or matrix remodeling appears to be of limited clinical relevance in breast cancer treatment so far. Further research is warranted to optimize intervention strategies and develop predictive tests for the relevance of targeting involved factors within the microenvironment in order to optimally personalize breast cancer treatment. (C) 2014 Elsevier Inc. All rights reserved. C1 [Nienhuis, H. H.; Gaykema, S. B. M.; Timmer-Bosscha, H.; Jalving, M.; de Vries, E. G. E.; Schroder, C. P.] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, NL-9700 RB Groningen, Netherlands. [Brouwers, A. H.; Lub-de Hooge, M. N.] Univ Groningen, Univ Med Ctr Groningen, Dept Nucl Med & Mol Imaging, NL-9700 RB Groningen, Netherlands. [Lub-de Hooge, M. N.] Univ Groningen, Univ Med Ctr Groningen, Dept Hosp & Clin Pharm, NL-9700 RB Groningen, Netherlands. [van der Vegt, B.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, NL-9700 RB Groningen, Netherlands. [Overmoyer, B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Schroder, CP (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, POB 30001, NL-9700 RB Groningen, Netherlands. EM c.p.schroder@umcg.nl RI van der Vegt, Bert/G-5887-2014; OI van der Vegt, Bert/0000-0002-2613-1506; Jalving, Mathilde/0000-0002-9142-9050 FU Dutch Cancer Society [RUG 2010-4739]; ERC [293445] FX Supported by Dutch Cancer Society grant RUG 2010-4739 and the ERC advanced grant 293445 (OnQview). NR 268 TC 6 Z9 8 U1 2 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAR PY 2015 VL 147 BP 63 EP 79 DI 10.1016/j.pharmthera.2014.11.004 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CC2QK UT WOS:000350189500006 PM 25444756 ER PT J AU Spring, JD Wood, NE Mueller-Pfeiffer, C Milad, MR Pitman, RK Orr, SP AF Spring, Justin D. Wood, Nellie E. Mueller-Pfeiffer, Christoph Milad, Mohammed R. Pitman, Roger K. Orr, Scott P. TI Prereactivation propranolol fails to reduce skin conductance reactivity to prepared fear-conditioned stimuli SO PSYCHOPHYSIOLOGY LA English DT Article DE Fear conditioning; Reconsolidation; Skin conductance; Propranolol; Posttraumatic stress disorder (PTSD) ID POSTTRAUMATIC-STRESS-DISORDER; DRIVEN TRAUMATIC IMAGERY; PUBLICATION RECOMMENDATIONS; ELECTRODERMAL MEASUREMENTS; MEMORY CONSOLIDATION; PTSD SYMPTOMS; RECONSOLIDATION; AMYGDALA; RESPONSES; REACTIVATION AB Pharmacologic blockade of memory reconsolidation has been demonstrated in fear-conditioned rodents and humans and may provide a means to reduce fearfulness in anxiety disorders and posttraumatic stress disorder. Studying the efficacy of potential interventions in clinical populations is challenging, creating a need for paradigms within which candidate reconsolidation-blocking interventions can be readily tested. We used videos of biologically prepared conditioned stimuli (tarantulas) to test the efficacy of propranolol in blocking reconsolidation of conditioned fear in healthy young adults. Strong differential conditioning, measured by skin conductance, was observed among a screened subset of participants during acquisition. However, subsequent propranolol failed to reduce reactivity to the reactivated conditioned stimulus. These results are consistent with other recent findings and point to a need for testing other candidate drugs. C1 [Spring, Justin D.; Wood, Nellie E.; Mueller-Pfeiffer, Christoph; Milad, Mohammed R.; Pitman, Roger K.; Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Mueller-Pfeiffer, Christoph] Cty St Gallen North, Psychiat Serv, Ctr Educ & Res COEUR, Wil, Switzerland. RP Orr, SP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 120 Second Ave, Charlestown, MA 02129 USA. EM scott_orr@hms.harvard.edu FU U.S. Army Medical Research and Material Command [W81XWH-11-2-0092 {DM102744}] FX This work was supported by a grant from the U.S. Army Medical Research and Material Command (award number W81XWH-11-2-0092 {DM102744}). NR 43 TC 12 Z9 12 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAR PY 2015 VL 52 IS 3 BP 407 EP 415 DI 10.1111/psyp.12326 PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA CC0QD UT WOS:000350039700012 PM 25224026 ER PT J AU Puchner, SB Lu, MT Mayrhofer, T Liu, T Pursnani, A Ghoshhajra, BB Truong, QA Wiviott, SD Fleg, JL Hoffmann, U Ferencik, M AF Puchner, Stefan B. Lu, Michael T. Mayrhofer, Thomas Liu, Ting Pursnani, Amit Ghoshhajra, Brian B. Truong, Quynh A. Wiviott, Stephen D. Fleg, Jerome L. Hoffmann, Udo Ferencik, Maros TI High-Risk Coronary Plaque at Coronary CT Angiography Is Associated with Nonalcoholic Fatty Liver Disease, Independent of Coronary Plaque and Stenosis Burden: Results from the ROMICAT II Trial SO RADIOLOGY LA English DT Article ID SPIRAL COMPUTED-TOMOGRAPHY; HEPATIC STEATOSIS; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC LESIONS; REACTIVE PROTEIN; UNITED-STATES; POPULATION; CALCIFICATION; SEVERITY; SCORE AB Purpose: To determine the association between nonalcoholic fatty liver disease (NAFLD) and the presence of high-risk coronary atherosclerotic plaque as assessed with coronary computed tomographic (CT) angiography. Materials and Methods: This study was approved by the local ethics committees; informed consent was obtained. Patients randomized to the coronary CT angiography arm of the Rule Out Myocardial Infarction using Computer Assisted Tomography, or ROMICAT, II trial who underwent both nonenhanced CT to assess calcium score and contrast material-enhanced coronary CT angiography were included. Readers assessed coronary CT angiography images for the presence of coronary plaque, significant stenosis (>= 50%), and high-risk plaque features (positive remodeling, CT attenuation < 30 HU, napkin-ring sign, spotty calcium). NAFLD was defined as hepatic steatosis at nonenhanced CT (liver minus spleen CT attenuation < 1 HU) without evidence of clinical liver disease, liver cirrhosis, or alcohol abuse. To determine the association between high-risk plaque and NAFLD, univariable and multivariable logistic regression analyses were performed, with high-risk plaque as a dependent variable and NAFLD, traditional risk factors, and extent of coronary atherosclerosis as independent variables. Results: Overall, 182 (40.9%) of 445 patients had CT evidence of NAFLD. High-risk plaque was more frequent in patients with NAFLD than in patients without NAFLD (59.3% vs 19.0%, respectively; P < .001). The association between NAFLD and high-risk plaque (odds ratio, 2.13; 95% confidence interval: 1.18, 3.85) persisted after adjusting for the extent and severity of coronary atherosclerosis and traditional risk factors. Conclusion: NAFLD is associated with advanced high-risk coronary plaque, independent of traditional cardiovascular risk factors and the extent and severity of coronary artery disease. (C) RSNA, 2014. C1 [Puchner, Stefan B.; Lu, Michael T.; Mayrhofer, Thomas; Liu, Ting; Pursnani, Amit; Ghoshhajra, Brian B.; Truong, Quynh A.; Hoffmann, Udo; Ferencik, Maros] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Puchner, Stefan B.; Lu, Michael T.; Mayrhofer, Thomas; Liu, Ting; Pursnani, Amit; Ghoshhajra, Brian B.; Truong, Quynh A.; Hoffmann, Udo; Ferencik, Maros] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Truong, Quynh A.; Ferencik, Maros] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Puchner, Stefan B.] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria. [Wiviott, Stephen D.] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, Sch Med, Boston, MA 02115 USA. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Puchner, SB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM sbpuchner@mgh.harvard.edu FU national Instittute of Health [U01HL092040, U01HL092022, 5T32 HL076136, 5K24HL113128, K23HL098370, L30HL093896] FX This research was supported by the national Instittute of Health (grant nos. U01HL092040, U01HL092022, 5T32 HL076136, 5K24HL113128, K23HL098370, L30HL093896, and 5T32 HL076136) NR 35 TC 18 Z9 18 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 MAR PY 2015 VL 274 IS 3 BP 693 EP 701 DI 10.1148/radiol.14140933 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CB9YK UT WOS:000349990500008 PM 25369449 ER PT J AU Mohamed, ASR Ruangskul, MN Awan, MJ Baron, CA Kalpathy-Cramer, J Castillo, R Castillo, E Guerrero, TM Kocak-Uzel, E Yang, JZ Court, LE Kantor, ME Gunn, GB Colen, RR Frank, SJ Garden, AS Rosenthal, DI Fuller, CD AF Mohamed, Abdallah S. R. Ruangskul, Manee-Naad Awan, Musaddiq J. Baron, Charles A. Kalpathy-Cramer, Jayashree Castillo, Richard Castillo, Edward Guerrero, Thomas M. Kocak-Uzel, Esengul Yang, Jinzhong Court, Laurence E. Kantor, Michael E. Gunn, G. Brandon Colen, Rivka R. Frank, Steven J. Garden, Adam S. Rosenthal, David I. Fuller, Clifton D. TI Quality Assurance Assessment of Diagnostic and Radiation Therapy-Simulation CT Image Registration for Head and Neck Radiation Therapy: Anatomic Region of Interest-based Comparison of Rigid and Deformable Algorithms SO RADIOLOGY LA English DT Article ID GUIDED RADIOTHERAPY; VALIDATION; SEGMENTATION; ACCURACY; TUMORS AB Purpose: To develop a quality assurance (QA) workflow by using a robust, curated, manually segmented anatomic region-of-interest (ROI) library as a benchmark for quantitative assessment of different image registration techniques used for head and neck radiation therapy-simulation computed tomography (CT) with diagnostic CT coregistration. Materials and Methods: Radiation therapy-simulation CT images and diagnostic CT images in 20 patients with head and neck squamous cell carcinoma treated with curative-intent intensity-modulated radiation therapy between August 2011 and May 2012 were retrospectively retrieved with institutional review board approval. Sixty-eight reference anatomic ROIs with gross tumor and nodal targets were then manually contoured on images from each examination. Diagnostic CT images were registered with simulation CT images rigidly and by using four deformable image registration (DIR) algorithms: atlas based, B-spline, demons, and optical flow. The resultant deformed ROIs were compared with manually contoured reference ROIs by using similarity coefficient metrics (ie, Dice similarity coefficient) and surface distance metrics (ie, 95% maximum Hausdorff distance). The nonparametric Steel test with control was used to compare different DIR algorithms with rigid image registration (RIR) by using the post hoc Wilcoxon signed-rank test for stratified metric comparison. Results: A total of 2720 anatomic and 50 tumor and nodal ROIs were delineated. All DIR algorithms showed improved performance over RIR for anatomic and target ROI conformance, as shown for most comparison metrics (Steel test, P < .008 after Bonferroni correction). The performance of different algorithms varied substantially with stratification by specific anatomic structures or category and simulation CT section thickness. Conclusion: Development of a formal ROI-based QA workflow for registration assessment demonstrated improved performance with DIR techniques over RIR. After QA, DIR implementation should be the standard for head and neck diagnostic CT and simulation CT allineation, especially for target delineation. (C) RSNA, 2014 C1 [Mohamed, Abdallah S. R.; Ruangskul, Manee-Naad; Awan, Musaddiq J.; Baron, Charles A.; Castillo, Richard; Castillo, Edward; Guerrero, Thomas M.; Kocak-Uzel, Esengul; Yang, Jinzhong; Court, Laurence E.; Kantor, Michael E.; Gunn, G. Brandon; Frank, Steven J.; Garden, Adam S.; Rosenthal, David I.; Fuller, Clifton D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Colen, Rivka R.] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, Boston, MA USA. [Castillo, Richard; Castillo, Edward; Guerrero, Thomas M.] Rice Univ, Dept Computat & Appl Math, Houston, TX USA. [Castillo, Edward; Guerrero, Thomas M.; Court, Laurence E.; Fuller, Clifton D.] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA. RP Fuller, CD (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Box 0097,1515 Holcombe Blvd, Houston, TX 77030 USA. EM cdfuller@mdanderson.org OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618; Fuller, Clifton/0000-0002-5264-3994; Yang, Jinzhong/0000-0002-9254-4501; Mohamed, Abdallah/0000-0003-2064-7613 FU National Institutes of Health [CA016672, K12 CA088084-14, L30 CA136381-02, K99/R00 LM009889, U01 CA154601, U24 CA180918, K01 CA181292, DP OD007044, R0 CA178495] FX This research was supported in part by National Institutes of Health (grant nos CA016672, K12 CA088084-14, L30 CA136381-02, K99/R00 LM009889, U01 CA154601 and U24 CA180918, K01 CA181292, DP OD007044, R0 CA178495). NR 37 TC 8 Z9 8 U1 1 U2 9 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2015 VL 274 IS 3 BP 752 EP 763 DI 10.1148/radiol.14132871 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CB9YK UT WOS:000349990500014 PM 25380454 ER PT J AU Zhang, M Lin, QX Lu, J Rong, DD Zhao, ZL Ma, QF Liu, HS Shu, N He, Y Li, KC AF Zhang, Miao Lin, Qixiang Lu, Jie Rong, Dongdong Zhao, Zhilian Ma, Qingfeng Liu, Hesheng Shu, Ni He, Yong Li, Kuncheng TI Pontine Infarction: Diffusion-Tensor Imaging of Motor Pathways-A Longitudinal Study SO RADIOLOGY LA English DT Article ID CORTICOSPINAL TRACT; CEREBRAL INFARCT; MR TRACTOGRAPHY; FIBER TRACKING; CHRONIC STROKE; RECOVERY; REORGANIZATION; CORTEX; DEGENERATION; INTEGRITY AB Purpose: To investigate the dynamic evolution of diffusion indexes in the corticospinal tract (CST) distal to a pontine infarct by using diffusion-tensor imaging, to determine the relationship of these indexes with clinical prognosis, and to explore the structural changes in the motor pathway during recovery. Materials and Methods: This study was approved by the institutional ethics committee, and written informed consent was obtained from each participant. Seventeen patients with pontine infarct underwent five diffusion-tensor imaging examinations during a period of 6 months (within 7 days of onset, 14, 30, 90, and 180 after onset). Fractional anisotropic values were measured in the medulla, cerebral peduncle, internal capsule, and centrum semiovale. Fractional anisotropic values of the CST in the ipsilateral side of the infarct were compared with those in the contralateral sides and those in control subjects by using the Student t test and one-way analysis of variance, and their relationships with clinical scores were analyzed by using Pearson correlation analysis. Reconstructions of the CST were performed. Structural changes of the damaged CST were followed up. Results: Fractional anisotropic ratios in the CST above the pons decreased significantly compared with those in the contralateral side and those in control subjects within 7 days, on day 14, and on day 30 after onset (P < .001). Fractional anisotropic ratios above the pons on day 14 correlated positively with Fugl-Meyer scores on day 90 (r = 0.771, P < .001) and day 180 (r = 0.730, P = .001). Follow-up diffusion-tensor tractographic images showed regeneration and reorganization of the motor pathways. Conclusion: Secondary degeneration of the CST can be detected at diffusion-tensor imaging in the early stages after pontine infarction, which could help predict the motor outcomes. Diffusion-tensor tractography can allow detection of regeneration and reorganization of the motor pathways during recovery. (C) RSNA, 2014 C1 [Zhang, Miao; Lu, Jie; Rong, Dongdong; Zhao, Zhilian; Li, Kuncheng] Capital Med Univ, Dept Radiol, Xuanwu Hosp, Beijing 100053, Peoples R China. [Ma, Qingfeng] Capital Med Univ, Dept Neurol, Xuanwu Hosp, Beijing 100053, Peoples R China. [Zhang, Miao; Lu, Jie; Rong, Dongdong; Zhao, Zhilian; Li, Kuncheng] Beijing Key Lab Magnet Resonance Imaging & Brain, Beijing, Peoples R China. [Lin, Qixiang; Shu, Ni; He, Yong] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [Lin, Qixiang; Shu, Ni; He, Yong] Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China. [Lin, Qixiang; Shu, Ni; He, Yong] Beijing Normal Univ, Ctr Collaborat & Innovat Brain & Learning Sci, Beijing 100875, Peoples R China. [Liu, Hesheng] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Liu, Hesheng] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Li, KC (reprint author), Capital Med Univ, Dept Radiol, Xuanwu Hosp, 45 Changchun St, Beijing 100053, Peoples R China. EM kuncheng.li@gmail.com FU NINDS NIH HHS [K25 NS069805] NR 29 TC 3 Z9 3 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2015 VL 274 IS 3 BP 841 EP 850 DI 10.1148/radiol.14140373 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CB9YK UT WOS:000349990500023 PM 25356962 ER PT J AU Samir, AE Dhyani, M Vij, A Bhan, AK Halpern, EF Mendez-Navarro, J Corey, KE Chung, RT AF Samir, Anthony E. Dhyani, Manish Vij, Abhinav Bhan, Atul K. Halpern, Elkan F. Mendez-Navarro, Jorge Corey, Kathleen E. Chung, Raymond T. TI Shear-Wave Elastography for the Estimation of Liver Fibrosis in Chronic Liver Disease: Determining Accuracy and Ideal Site for Measurement SO RADIOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; MAGNETIC-RESONANCE ELASTOGRAPHY; TRANSIENT ELASTOGRAPHY; HEPATOCELLULAR-CARCINOMA; STIFFNESS MEASUREMENT; UNITED-STATES; VIRUS; METAANALYSIS; PERFORMANCE; STEATOSIS AB Purpose: To evaluate the accuracy of shear-wave elastography (SWE) for staging liver fibrosis in patients with diffuse liver disease (including patients with hepatitis C virus [HCV]) and to determine the relative accuracy of SWE measurements obtained from different hepatic acquisition sites for staging liver fibrosis. Materials and Methods: The institutional review board approved this single-institution prospective study, which was performed between January 2010 and March 2013 in 136 consecutive patients who underwent SWE before their scheduled liver biopsy (age range, 18-76 years; mean age, 49 years; 70 men, 66 women). Informed consent was obtained from all patients. SWE measurements were obtained at four sites in the liver. Biopsy specimens were reviewed in a blinded manner by a pathologist using METAVIR criteria. SWE measurements and biopsy results were compared by using the Spearman correlation and receiver operating characteristic (ROC) curve analysis. Results: SWE values obtained at the upper right lobe showed the highest correlation with estimation of fibrosis (r = 0.41, P < .001). Inflammation and steatosis did not show any correlation with SWE values except for values from the left lobe, which showed correlation with steatosis (r = 0.24, P = .004). The area under the ROC curve (AUC) in the differentiation of stage F2 fibrosis or greater, stage F3 fibrosis or greater, and stage F4 fibrosis was 0.77 (95% confidence interval [CI]: 0.68, 0.86), 0.82 (95% CI: 0.75, 0.91), and 0.82 (95% CI: 0.70, 0.95), respectively, for all subjects who underwent liver biopsy. The corresponding AUCs for the subset of patients with HCV were 0.80 (95% CI: 0.67, 0.92), 0.82 (95% CI: 0.70, 0.95), and 0.89 (95% CI: 0.73, 1.00). The adjusted AUCs for differentiating stage F2 or greater fibrosis in patients with chronic liver disease and those with HCV were 0.84 and 0.87, respectively. Conclusion: SWE estimates of liver stiffness obtained from the right upper lobe showed the best correlation with liver fibrosis severity and can potentially be used as a noninvasive test to differentiate intermediate degrees of liver fibrosis in patients with liver disease. (C) RSNA, 2014 C1 [Samir, Anthony E.; Dhyani, Manish] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Bhan, Atul K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA. [Corey, Kathleen E.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hepatol,Liver & GI Div,Dept Med, Boston, MA 02114 USA. [Vij, Abhinav] Bryn Mawr Hosp, Dept Radiol, Bryn Mawr, PA USA. [Mendez-Navarro, Jorge] Hosp Especialidades Ctr Med La Raza, Dept Gastroenterol, Natl Med Ctr, CMN Siglo 21,IMSS, Mexico City, DF, Mexico. RP Samir, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM asamir@partners.org OI Samir, Anthony/0000-0002-7801-8724; Dhyani, Manish/0000-0002-2651-1859 FU National Institutes of Health [DK078772] FX R.T.C. supported by the National Institutes of Health (grant DK078772). NR 38 TC 19 Z9 22 U1 1 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2015 VL 274 IS 3 BP 888 EP 896 DI 10.1148/radiol.14140839 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CB9YK UT WOS:000349990500029 PM 25393946 ER PT J AU Sheth, RA Arellano, RS Uppot, RN Samir, AE Goyal, L Zhu, AX Gervais, DA Mahmood, U AF Sheth, Rahul A. Arellano, Ronald S. Uppot, Raul N. Samir, Anthony E. Goyal, Lipika Zhu, Andrew X. Gervais, Debra A. Mahmood, Umar TI Prospective Trial with Optical Molecular Imaging for Percutaneous Interventions in Focal Hepatic Lesions SO RADIOLOGY LA English DT Article ID INDOCYANINE GREEN; HEPATOCELLULAR-CARCINOMA; RESECTION; SURGERY; BIOPSY AB Purpose: To demonstrate the clinical translation of optical molecular imaging (OMI) for the localization of focal hepatic lesions during percutaneous hepatic interventions. Materials and Methods: Institutional review board approval was obtained for this prospective, single-center, HIPAA-compliant trial. Patients who were suspected of having hepatocellular carcinoma or liver metastases from colorectal cancer and were scheduled for percutaneous liver biopsy or thermal ablation were eligible for this study. Patients (n = 5) received 0.5 mg per kilogram of body weight of indocyanine green (ICG) intravenously 24 hours prior to their scheduled procedure in this study. Intraprocedurally, a handheld device composed of an endoscope that fits coaxially through a standard 17-gauge introducer needle was advanced into the liver, and real-time measurements of ICG fluorescence were obtained. A point-of-care fluorescence imaging system was used to image ICG fluorescence in biopsy samples. Target-to-background ratios (TBRs) were calculated by dividing the mean fluorescence intensity in the lesion by the mean fluorescence intensity in the adjacent liver parenchyma. The reference standard for determination of proper needle positioning in patients undergoing biopsy was final pathologic analysis of biopsy specimens or follow-up imaging. Results: Intraprocedural OMI was successfully performed in six lesions (two lesions in patient 3) in five patients. The median size of the targeted lesions was 16 mm (range, 10-21 mm). Four of five biopsies (80%) yielded an accurate pathologic diagnosis, and one biopsy specimen showed benign liver parenchyma; both ablated lesions showed no residual disease 1 month after the procedure. The median overall added procedure time to perform OMI was 2 minutes. ICG was found to localize with TBRs greater than 2.0 (median, 7.9; range, 2.4-13.4) in all target lesions. No trial-related adverse events were reported. Conclusion: The clinical translation of OMI to percutaneous hepatic interventions was demonstrated. (C) RSNA, 2014 C1 [Sheth, Rahul A.; Arellano, Ronald S.; Uppot, Raul N.; Samir, Anthony E.; Gervais, Debra A.; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Goyal, Lipika; Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Hematol Oncol, Charlestown, MA 02129 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM umahmood@mgh.harvard.edu OI Samir, Anthony/0000-0002-7801-8724 FU National Institutes of Health [U01CA084301, P50CA127003] FX This research was supported by the National Institutes of Health (grants U01CA084301 and P50CA127003). NR 18 TC 8 Z9 9 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2015 VL 274 IS 3 BP 917 EP 926 DI 10.1148/radiol.14141308 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CB9YK UT WOS:000349990500032 PM 25302707 ER PT J AU Kikinis, Z Fitzsimmons, J Dunn, C Vu, MA Makris, N Bouix, S Goldstein, JM Mesholam-Gately, RI Petryshen, T Del Re, EC Wojcik, J Seidman, LJ Kubicki, M AF Kikinis, Zora Fitzsimmons, Jennifer Dunn, Chandler Mai-Anh Vu Makris, Nikos Bouix, Sylvain Goldstein, Jill M. Mesholam-Gately, Raquelle I. Petryshen, Tracey del Re, Elisabetta C. Wojcik, Joanne Seidman, Larry J. Kubicki, Marek TI Anterior commissural white matter fiber abnormalities in first-episode psychosis: A tractography study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE First-episode schizophrenia; Anterior commissure (AC); Diffusion Tensor Magnetic Resonance Imaging (dMRI); Fractional anisotropy (FA); Radial diffusivity (RD); Tractography ID DIFFUSION-TENSOR; CORPUS-CALLOSUM; RADIAL DIFFUSIVITY; TEMPORAL-LOBE; FUNCTIONAL CONNECTIVITY; FRACTIONAL ANISOTROPY; CHRONIC-SCHIZOPHRENIA; CORTICAL REGIONS; RHESUS-MONKEY; HUMAN BRAIN AB Background: The Anterior Commissure (AC) is an important interhemispheric pathway that connects contralateral temporal lobes and orbitofrontal areas. The role of the AC is not yet well understood, although abnormalities in this white matter tract have been reported in patients diagnosed with chronic schizophrenia. However, it is not known whether changes in the AC are present at earlier stages of the disease. Methods: Diffusion Magnetic Resonance Images (dMRI) were acquired from 17 First Episode Schizophrenia Patients (FESZ) and 20 healthy controls. The AC was reconstructed using a streamline tractography approach. DMRI measures, including Fractional Anisotropy (FA), Trace, Axial Diffusivity (AD) and Radial Diffusivity (RD) were computed in order to assess microstructural changes in the AC. Results: FA was reduced, while trace and RD showed increases in FESZ. AD did not show differences between groups. Conclusion: The observed changes in these dMRI measures, namely reductions in FA and increases in trace and RD, without changes in AD, likely point to myelin abnormalities of this white matter tract, and provide evidence of white matter pathology extant in the early phases of schizophrenia. (C) 2015 Elsevier B.V. All rights reserved. C1 [Kikinis, Zora; Fitzsimmons, Jennifer; Dunn, Chandler; Mai-Anh Vu; Makris, Nikos; Bouix, Sylvain; Goldstein, Jill M.; del Re, Elisabetta C.; Kubicki, Marek] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02114 USA. [Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02114 USA. [Mesholam-Gately, Raquelle I.; Wojcik, Joanne; Seidman, Larry J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Publ Psychiat Div, Boston, MA 02114 USA. [Petryshen, Tracey] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Petryshen, Tracey] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Petryshen, Tracey] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [del Re, Elisabetta C.] VA Boston Healthcare Syst, Brockton, MA USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Kikinis, Z (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, 1249 Boylston St, Boston, MA 02114 USA. EM zora@bwh.harvard.edu FU NIH [R01 AG04252, R01 MH102377, P50MH080272]; NIMH [R01MH082918]; Veterans Administration Merit Review; T32 Stuart T. Hauser Clinical Research Training Program in Biological and Social Psychiatry; Commonwealth Research Center [SCDMH82101008006]; Clinical Translational Science Award [UL1RR025758]; Beth Israel Deaconess Medical Center from the National Center for Research Resources FX This work was supported by NIH R01 AG04252; NIH R01 MH102377; NIMH R01MH082918; NIH P50MH080272; Veterans Administration Merit Review; T32 Stuart T. Hauser Clinical Research Training Program in Biological and Social Psychiatry; the Commonwealth Research Center (SCDMH82101008006) and by the Clinical Translational Science Award UL1RR025758 to Harvard University and Beth Israel Deaconess Medical Center from the National Center for Research Resources. NR 61 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 2015 VL 162 IS 1-3 BP 29 EP 34 DI 10.1016/j.schres.2015.01.037 PG 6 WC Psychiatry SC Psychiatry GA CB9QI UT WOS:000349966400005 PM 25667192 ER PT J AU Tabak, NT Green, MF Wynn, JK Proudfit, GH Altshuler, L Horan, WP AF Tabak, Naomi T. Green, Michael F. Wynn, Jonathan K. Proudfit, Greg H. Altshuler, Lori Horan, William P. TI Perceived emotional intelligence is impaired and associated with poor community functioning in schizophrenia and bipolar disorder SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Bipolar disorder; Emotion; Emotional intelligence ID META-MOOD SCALE; RATING-SCALE; LIFE SATISFACTION; NEGATIVE SYMPTOMS; BEHAVIOR-THERAPY; I DISORDER; MINDFULNESS; VALIDITY; INDIVIDUALS; RELIABILITY AB Schizophrenia and bipolar disorder have been associated with shared and distinct emotion processing abnormalities. Initial findings indicate that these disorders differ with respect to the domain of emotional intelligence (EI). Individuals with schizophrenia display deficits on performance measures of EI, whereas those with bipolar disorder do not. However, no research has examined patients' subjective beliefs about their own EI (referred to as "perceived EI"). This study examined perceived EI, assessed with the Trait Meta-Mood Scale (TMMS), and its clinical and functional correlates in outpatients with schizophrenia (n = 35) or bipolar disorder I (n = 38) and matched healthy controls (n = 35). The TMMS includes three subscales that assess beliefs about one's ability to attend to (Attention to Feelings), understand (Clarity of Feelings), and repair emotions (Mood Repair). Participants in the clinical groups also completed community functioning and symptom assessments. Both clinical groups reported significantly lower perceived EI than controls, but did not differ from each other. Higher total TMMS correlated with higher levels of independent living in the schizophrenia group (r =. 36) and better social functioning in the bipolar group (r = .61). In addition, although higher Attention to Feelings scores correlated with greater psychiatric symptoms in the schizophrenia group, higher scores across all subscales correlated with less manic symptoms in the bipolar group. The findings suggest that perceived EI is impaired and related to community functioning in both disorders. Published by Elsevier B.V. C1 [Tabak, Naomi T.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90073 USA. [Tabak, Naomi T.; Green, Michael F.; Wynn, Jonathan K.; Horan, William P.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Green, Michael F.; Wynn, Jonathan K.; Altshuler, Lori; Horan, William P.] UCLA Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Proudfit, Greg H.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY USA. RP Horan, WP (reprint author), Univ Calif Los Angeles, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM horan@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIMH [MH091468, MH065707, MH43292] FX Funding for the current study was provided by NIMH Grants MH091468 (William P. Horan, Ph.D.) and MH065707 and MH43292 (Michael F. Green, PhD). NR 55 TC 5 Z9 5 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 2015 VL 162 IS 1-3 BP 189 EP 195 DI 10.1016/j.schres.2014.12.005 PG 7 WC Psychiatry SC Psychiatry GA CB9QI UT WOS:000349966400031 PM 25579055 ER PT J AU Gao, R Chen, S Kobayashi, M Yu, H Zhang, YC Wan, Y Young, SK Soltis, A Yu, M Vemula, S Fraenkel, E Cantor, A Antipin, Y Xu, Y Yoder, MC Wek, RC Ellis, SR Kapur, R Zhu, XF Liu, Y AF Gao, Rui Chen, Sisi Kobayashi, Michihiro Yu, Hao Zhang, Yingchi Wan, Yang Young, Sara K. Soltis, Anthony Yu, Ming Vemula, Sasidhar Fraenkel, Ernest Cantor, Alan Antipin, Yevgeniy Xu, Yang Yoder, Mervin C. Wek, Ronald C. Ellis, Steven R. Kapur, Reuben Zhu, Xiaofan Liu, Yan TI Bmi1 Promotes Erythroid Development Through Regulating Ribosome Biogenesis SO STEM CELLS LA English DT Article DE Bmi1; Ribosome biogenesis; Erythroid differentiation; p53; Ribosomopathies ID DIAMOND-BLACKFAN ANEMIA; POLYCOMB GROUP PROTEINS; HEMATOPOIETIC STEM-CELLS; PROGENITOR CELLS; GENE-EXPRESSION; MAINTENANCE; APOPTOSIS; MYC; RIBOSOMOPATHIES; ERYTHROPOIESIS AB While Polycomb group protein Bmi1 is important for stem cell maintenance, its role in lineage commitment is largely unknown. We have identified Bmi1 as a novel regulator of erythroid development. Bmi1 is highly expressed in mouse erythroid progenitor cells and its deficiency impairs erythroid differentiation. BMI1 is also important for human erythroid development. Furthermore, we discovered that loss of Bmi1 in erythroid progenitor cells results in decreased transcription of multiple ribosomal protein genes and impaired ribosome biogenesis. Bmi1 deficiency stabilizes p53 protein, leading to upregulation of p21 expression and subsequent G0/G1 cell cycle arrest. Genetic inhibition of p53 activity rescues the erythroid defects seen in the Bmi1 null mice, demonstrating that a p53-dependent mechanism underlies the pathophysiology of the anemia. Mechanistically, Bmi1 is associated with multiple ribosomal protein genes and may positively regulate their expression in erythroid progenitor cells. Thus, Bmi1 promotes erythroid development, at least in part through regulating ribosome biogenesis. Ribosomopathies are human disorders of ribosome dysfunction, including Diamond-Blackfan anemia (DBA) and 5q- syndrome, in which genetic abnormalities cause impaired ribosome biogenesis, resulting in specific clinical phenotypes. We observed that BMI1 expression in human hematopoietic stem and progenitor cells from patients with DBA is correlated with the expression of some ribosomal protein genes, suggesting that BMI1 deficiency may play a pathological role in DBA and other ribosomopathies. C1 [Gao, Rui; Kobayashi, Michihiro; Yu, Hao; Vemula, Sasidhar; Yoder, Mervin C.; Kapur, Reuben; Liu, Yan] Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN 46202 USA. [Chen, Sisi; Young, Sara K.; Wek, Ronald C.; Liu, Yan] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46204 USA. [Zhang, Yingchi; Wan, Yang; Zhu, Xiaofan] Chinese Acad Med Sci, Inst Hematol, Dept Pediat, State Key Lab Expt Hematol, Tianjin, Peoples R China. [Zhang, Yingchi; Wan, Yang; Zhu, Xiaofan] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China. [Zhang, Yingchi; Wan, Yang; Zhu, Xiaofan] Peking Union Med Coll, Tianjin, Peoples R China. [Soltis, Anthony; Fraenkel, Ernest] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Yu, Ming; Cantor, Alan] Harvard Univ, Sch Med, Div Med Sci, Childrens Hosp Boston, Boston, MA USA. [Yu, Ming; Cantor, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. [Antipin, Yevgeniy] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10021 USA. [Xu, Yang] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92103 USA. [Ellis, Steven R.] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40292 USA. RP Liu, Y (reprint author), Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN 46202 USA. EM liu219@iu.edu OI Soltis, Anthony/0000-0002-3394-1275; Fraenkel, Ernest/0000-0001-9249-8181 FU Department of Defense (DoD) Career Development Award [CA120373]; St. Baldrick's Foundation Scholar Award; Elsa Pardee Foundation Cancer Research Award; Alex's Lemonade Stand Foundation Research Award; American Cancer Society Institutional Research Grant; Indiana University Simon Cancer Center pilot project grant; Indiana University Biomedical Research Grant FX We would like to thank Dr. Martin van Lohuizen (The Netherlands Cancer Institute, The Netherlands) for providing the Bmi1 knockout mice. We are also grateful to Dr. Atsushi Iwama (Chiba University, Japan) for providing BMI1-shRNAs and to Dr. Schuringa (University of Groningen, Groningen, The Netherlands) for providing MIGR1-BMI1 plasmid. This work was supported in part by the Department of Defense (DoD) Career Development Award CA120373 (Y.L.), an St. Baldrick's Foundation Scholar Award (Y.L.), an Elsa Pardee Foundation Cancer Research Award (Y.L.), an Alex's Lemonade Stand Foundation Research Award (Y.L.), an American Cancer Society Institutional Research Grant (Y.L.), an Indiana University Simon Cancer Center pilot project grant (Y.L.), and an Indiana University Biomedical Research Grant (Y.L.). We acknowledge the In Vivo Therapeutics Core of the Indiana University Simon Cancer Center as well as the nursing staff and Dr. Arthur Baluyut at the St. Vincent Hospital (Indianapolis, IN) for providing umbilical cord blood samples for this study. We also would like to thank Marilyn Wales for helping in the preparation of the manuscript. NR 53 TC 5 Z9 5 U1 2 U2 9 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 MAR PY 2015 VL 33 IS 3 BP 925 EP 938 DI 10.1002/stem.1896 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA CB7ZZ UT WOS:000349849000026 PM 25385494 ER PT J AU Howitt, BE Hanamornroongruang, S Lin, DI Conner, JE Schulte, S Horowitz, N Crum, CP Meserve, EE AF Howitt, Brooke E. Hanamornroongruang, Suchanan Lin, Douglas I. Conner, James E. Schulte, Stephanie Horowitz, Neil Crum, Christopher P. Meserve, Emily E. TI Evidence for a Dualistic Model of High-grade Serous Carcinoma BRCA Mutation Status, Histology, and Tubal Intraepithelial Carcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE fallopian tube; neoplasia; serous carcinoma; BRCA; endometrioid; tubal intraepithelial carcinoma; risk-reduction salpingo-oophorectomy ID OVARIAN-CANCER; FALLOPIAN-TUBE; SALPINGO-OOPHORECTOMY; BREAST-CANCER; NEOPLASIA; WOMEN; EPITHELIUM; PRECURSOR; RISK; CARCINOGENESIS AB Most early adnexal carcinomas detected in asymptomatic women with germline BRCA mutations (BRCA(+)) present as serous tubal intraepithelial carcinomas (STIC). However, STICs are found in only similar to 40% of symptomatic high-grade serous carcinomas (HGSCs) and less frequently in pseudoendo-metrioid variants of HGSC. Consecutive cases of untreated HGSC from BRCA(+) and BRCA(-) women with detailed fallopian tube examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined, and tumors were classified morphologically as SET ("SET", >50% solid, pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET tumors trended toward a higher frequency in BRCA(+) versus BRCA(-) women (50% vs. 28%, P = 0.11), had a significantly younger mean age than those with classic HGSC in BRCA(-) women (mean 56.2 vs. 64.8 y, P = 0.04), and displayed a better clinical outcome in both groups combined (P = 0.024). STIC was significantly more frequent in tumors from the BRCA(-) cohort (66% vs. 31%, P = 0.017) and specifically the BRCA(-) tumors with classic morphology (83%) versus those with SET morphology (22%, P = 0.003). Overall, several covariables histology, BRCA status, age, coexisting STIC, and response to therapy-define 2 categories of HGSC with differences in precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic HGSC model that could shed light on the differences in frequency of STIC between symptomatic and asymptomatic women with HGSC. This model emphasizes the need for further study of HGSC precursors to determine their relevance to the prevention of this lethal malignancy. C1 [Howitt, Brooke E.; Lin, Douglas I.; Conner, James E.; Schulte, Stephanie; Crum, Christopher P.; Meserve, Emily E.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Horowitz, Neil] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Horowitz, Neil] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hanamornroongruang, Suchanan] Mahidol Univ, Siriraj Hosp, Dept Pathol, Bangkok 10700, Thailand. RP Crum, CP (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM ccrum@partners.org FU Department of Defense [W81XWH-10-1-0289] FX Supported by a grant from the Department of Defense (W81XWH-10-1-0289 to C.P.C.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 25 TC 18 Z9 18 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2015 VL 39 IS 3 BP 287 EP 293 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA CB7JS UT WOS:000349803400001 PM 25581732 ER PT J AU Reder, L Della-Torre, E Stone, JH Mori, M Song, P AF Reder, Lindsay Della-Torre, Emanuel Stone, John H. Mori, Matthew Song, Phillip TI Clinical Manifestations of IgG4-Related Disease in the Pharynx: Case Series and Review of the Literature SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE fibrosis; IgG4-related disease; larynx; pharynx; rituximab ID HEAD; NECK AB Objective: The objective of this report is to characterize IgG4-related disease (IgG4-RD) as it is manifested in the head and neck and describe a series of patients with a rarely described presentation in laryngopharyngeal subsites. Methods: Here, we illustrate the presentation and clinical course of 3 patients with laryngopharyngeal manifestations of IgG4-RD, including the manner of diagnosis and effective treatment. Results: Three patients with laryngopharyngeal lesions were ultimately diagnosed with IgG4-RD after lengthy work-up. The diagnostic criteria and treatment protocols are explained. Conclusion: IgG4-related disease is a fibroinflannmatory disorder now described in almost every organ system. The head and neck regions are among the most common areas of involvement, however, reports of laryngopharyngeal involvement are rare. We also summarize current knowledge of this entity and discuss established diagnostic criteria and clinical findings. C1 [Reder, Lindsay] Univ So Calif, Dept Otolaryngol Head & Neck Surg, Los Angeles, CA USA. [Della-Torre, Emanuel] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Unit Med & Clin Immunol, Milan, Italy. [Della-Torre, Emanuel; Stone, John H.; Mori, Matthew; Song, Phillip] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Mori, Matthew; Song, Phillip] Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02481 USA. [Mori, Matthew; Song, Phillip] Massachusetts Eye & Ear Infirm, Ctr Neurolaryngol, Boston, MA 02481 USA. RP Song, P (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02481 USA. EM phillip_song@meei.harvard.edu NR 18 TC 3 Z9 3 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-4894 EI 1943-572X J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAR PY 2015 VL 124 IS 3 BP 173 EP 178 DI 10.1177/0003489414549574 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA CB3FD UT WOS:000349512700001 PM 25204708 ER PT J AU Marcum, ZA Driessen, J Thorpe, CT Donohue, JM Gellad, WF AF Marcum, Zachary A. Driessen, Julia Thorpe, Carolyn T. Donohue, Julie M. Gellad, Walid F. TI Regional Variation in Use of a New Class of Antidiabetic Medication Among Medicare Beneficiaries: The Case of Incretin Mimetics SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE Medicare; diabetes; pharmacoepidemiology; regional variation ID PRESCRIPTION DRUG-USE; GEOGRAPHIC-VARIATION; PART-D; CLINICAL-USE; PATIENT; DETERMINANTS; PHYSICIANS; INHIBITORS; THERAPIES; COHORT AB Background: When incretin mimetic (IM) medications were introduced in 2005, their effectiveness compared with other less-expensive second-line diabetes therapies was unknown, especially for older adults. Physicians likely had some uncertainty about the role of IMs in the diabetes treatment armamentarium. Regional variation in uptake of IMs may be a marker of such uncertainty. Objective: To investigate the extent of regional variation in the use of IMs among beneficiaries and estimate the cost implications for Medicare. Methods: This was a cross-sectional analysis of 2009-2010 claims data from a nationally representative sample of 238 499 Medicare Part D beneficiaries aged >= 65 years, who were continuously enrolled in fee-for-service Medicare and Part D and filled >= 1 antidiabetic prescription. Beneficiaries were assigned to I of 306 hospital-referral regions (HRRs) using ZIP codes. The main outcome was adjusted proportion of antidiabetic users in an HRR receiving an IM. Results: Overall, 29 933 beneficiaries (12.6%) filled an IM prescription, including 26 939 (11.3%) for sitagliptin or saxagliptin and 3718 (1.6%) for exenatide or liraglutide. The adjusted proportion of beneficiaries using IMs varied more than 3-fold across HRRs, from 5th and 95th percentiles of 5.2% to 17.0%. Compared with non-1M users, IM users faced a 155% higher annual Part D plan ($1067 vs $418) and 144% higher patient ($369 vs $151) costs for antidiabetic prescriptions. Conclusion: Among older Part D beneficiaries using antidiabetic drugs, substantial regional variation exists in the use of IMs, not accounted for by sociodemographics and health status. IM use was associated with substantially greater costs for Part D plans and beneficiaries. C1 [Marcum, Zachary A.; Driessen, Julia; Thorpe, Carolyn T.; Donohue, Julie M.; Gellad, Walid F.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Thorpe, Carolyn T.; Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Marcum, ZA (reprint author), Univ Pittsburgh, Sch Med, Div Geriatr Med, 3471 Fifth Ave Suite 500, Pittsburgh, PA 15213 USA. EM zam12@pitt.edu OI Donohue, Julie/0000-0003-2418-6017 FU National Institute on Aging [P30 AG024827, K07AG033174, R01AG027017]; AHRQ [R01HS018721]; VA HSR&D Career Development Award [CDA 09-207]; NHLBI, a pilot grant from the RAND-University of Pittsburgh Health Institute (RUPHI) [R01HL119246]; National Center for Research Resources (NCRR), a component of the National Institutes of Health [UL1 RR024153] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by National Institute on Aging Grants (P30 AG024827; K07AG033174; R01AG027017), and an AHRQ grant (R01HS018721). WFG was supported by a VA HSR&D Career Development Award (CDA 09-207). JMD and WFG were partially supported by R01HL119246 from NHLBI, a pilot grant from the RAND-University of Pittsburgh Health Institute (RUPHI), and Grant Number UL1 RR024153 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health. NR 27 TC 1 Z9 1 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAR PY 2015 VL 49 IS 3 BP 285 EP 292 DI 10.1177/1060028014563951 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CB6NI UT WOS:000349743300003 PM 25515869 ER PT J AU Robinson, TN Rosenthal, RA AF Robinson, Thomas N. Rosenthal, Ronnie A. TI Optimizing the Geriatric Preoperative Assessment The Use of Functional Dependence and Beyond SO ANNALS OF SURGERY LA English DT Editorial Material ID SURGICAL OUTCOMES; INTENSITY; CARE; LIFE; END C1 [Robinson, Thomas N.] Denver VA Med Ctr, Dept Surg, Denver, CO 80220 USA. [Rosenthal, Ronnie A.] Yale Univ, Sch Med, Dept Surg, West Haven, CT 06516 USA. RP Robinson, TN (reprint author), Denver VA Med Ctr, Dept Surg, 1055 Clermont St 112, Denver, CO 80220 USA. EM thomas.robinson@ucclenver.edu NR 9 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 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAR PY 2015 VL 261 IS 3 BP 438 EP 439 DI 10.1097/SLA.0000000000001132 PG 2 WC Surgery SC Surgery GA CB3WK UT WOS:000349559900036 PM 25654561 ER PT J AU Chung, JW Ju, MH Kinnier, CV Sohn, MW Bilimoria, KY AF Chung, Jeanette W. Ju, Mila H. Kinnier, Christine V. Sohn, Min-Woong Bilimoria, Karl Y. TI Postoperative Venous Thromboembolism Outcomes Measure Analytic Exploration of Potential Misclassification of Hospital Quality Due to Surveillance Bias SO ANNALS OF SURGERY LA English DT Editorial Material C1 [Chung, Jeanette W.; Ju, Mila H.; Kinnier, Christine V.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr, Dept Surg, Chicago, IL 60611 USA. [Chung, Jeanette W.; Ju, Mila H.; Kinnier, Christine V.; Bilimoria, Karl Y.] NW Mem Hosp, Chicago, IL 60611 USA. [Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sohn, Min-Woong] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. RP Bilimoria, KY (reprint author), Northwestern Univ, NW Mem Hosp, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr,Dept Surg, 676 St Clair St,Arkes Pavil Suite 6-650, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu RI Sohn, Min-Woong/C-3560-2015 OI Sohn, Min-Woong/0000-0002-9474-2907 FU AHRQ HHS [R21 HS021857, R21HS021857]; NHLBI NIH HHS [T32 HL094293, 5T32HL094293] NR 3 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAR PY 2015 VL 261 IS 3 BP 443 EP 444 DI 10.1097/SLA.0000000000000850 PG 2 WC Surgery SC Surgery GA CB3WK UT WOS:000349559900038 PM 25119123 ER PT J AU Artinyan, A Orcutt, ST Anaya, DA Richardson, P Chen, GJ Berger, DH AF Artinyan, Avo Orcutt, Sonia T. Anaya, Daniel A. Richardson, Peter Chen, G. John Berger, David H. TI Infectious Postoperative Complications Decrease Long-term Survival in Patients Undergoing Curative Surgery for Colorectal Cancer A Study of 12,075 Patients SO ANNALS OF SURGERY LA English DT Article DE colorectal cancer; postoperative complications; surgery; surgical site infections; survival ID QUALITY IMPROVEMENT PROGRAM; ANASTOMOTIC LEAKAGE; RECTAL-CANCER; COLON-CANCER; RISK-FACTORS; SURGICAL COMPLICATIONS; RESECTION; MORTALITY; MORBIDITY; IMPACT AB Objective: We sought to characterize the effect of postoperative complications on long-term survival after colorectal cancer (CRC) resection. Background: The impact of early morbidity on long-term survival after curative-intent CRC surgery remains controversial. Methods: The Veterans Affairs Surgical Quality Improvement Program and Central Cancer Registry databases were linked to acquire perioperative and cancer-specific data for 12,075 patients undergoing resection for nonmetastatic CRC (1999-2009). Patients were categorized by presence of any complication within 30 days and by type of complication (noninfectious vs infectious). Univariate and multivariate survival analyses adjusted for patient, disease, and treatment factors were performed, excluding early deaths (<90 days). Subset analysis was performed to determine the specific impact of severe postoperative infections. Results: The overall morbidity and infectious complication rates were 27.8% and 22.5%, respectively. Patients with noninfectious postoperative complications were older, had lower preoperative serum albumin, had worse functional status, and had higher American Society of Anesthesiologists scores than patients with infectious complications and without complications (all P < 0.001). The presence of any complication was independently associated with decreased long-term survival [hazard ratio, 1.24; 95% confidence interval (1.15-1.34)]. Multivariate analysis by complication type demonstrated increased risk only with infectious complications [hazard ratio, 1.31; 95% confidence interval (1.21-1.42)]. Subset analysis demonstrated this effect predominantly in patients with severe infections [hazard ratio, 1.41; 95% confidence interval (1.15-1.73)]. Conclusions: The presence of postoperative complications after CRC resection is associated with decreased long-term survival, independent of patient, disease, and treatment factors. The impact on long-term outcome is primarily driven by infectious complications, particularly severe postoperative infections. C1 [Artinyan, Avo; Anaya, Daniel A.; Berger, David H.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Artinyan, Avo; Orcutt, Sonia T.; Anaya, Daniel A.; Berger, David H.] Baylor Coll Med, Dept Surg, Div Gen Surg & Surg Oncol, Houston, TX 77030 USA. [Anaya, Daniel A.; Richardson, Peter; Chen, G. John; Berger, David H.] Vet Affairs Ctr Innovat Qual Effectiveness & Safe, Houston, TX USA. [Richardson, Peter; Chen, G. John] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Artinyan, A (reprint author), Baylor Coll Med, Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM artinyan@bcm.edu NR 39 TC 29 Z9 30 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAR PY 2015 VL 261 IS 3 BP 497 EP 505 DI 10.1097/SLA.0000000000000854 PG 9 WC Surgery SC Surgery GA CB3WK UT WOS:000349559900046 PM 25185465 ER PT J AU Konstantinidis, IT Ferrone, CR AF Konstantinidis, Ioannis T. Ferrone, Cristina R. TI Retrospective Studies and Pancreatic Adenocarcinoma: How Far Can We Backdate? Reply SO ANNALS OF SURGERY LA English DT Letter C1 [Konstantinidis, Ioannis T.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Konstantinidis, IT (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM cferrone@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAR PY 2015 VL 261 IS 3 BP E84 EP E84 DI 10.1097/SLA.0000000000000417 PG 1 WC Surgery SC Surgery GA CB3WK UT WOS:000349559900029 PM 24368656 ER PT J AU Palter, VN Grantcharov, TP AF Palter, Vanessa N. Grantcharov, Teodor P. TI Development and Validation of a Comprehensive Curriculum to Teach an Advanced Minimally Invasive Procedure Reply SO ANNALS OF SURGERY LA English DT Letter ID SKILLS LABORATORIES; NATIONAL-SURVEY C1 [Palter, Vanessa N.] Univ Toronto, Toronto, ON, Canada. [Grantcharov, Teodor P.] Univ Toronto, St Michaels Hosp, Massachusetts Gen Hosp, Boston, MA USA. RP Palter, VN (reprint author), Univ Toronto, Toronto, ON, Canada. EM vanessa.palter@utoronto.ca NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAR PY 2015 VL 261 IS 3 BP E72 EP E73 DI 10.1097/SLA.0000000000000480 PG 2 WC Surgery SC Surgery GA CB3WK UT WOS:000349559900014 PM 25664536 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Modeling Lengthy Work-ups in Gastrointestinal Bleeding SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Gastrointestinal Bleeding; Markov Chain; Medical Decision Analysis; Modeling ID DOUBLE-BALLOON ENTEROSCOPY; COST-EFFECTIVENESS; CAPSULE ENDOSCOPY; COLORECTAL-CANCER; DECISION-ANALYSIS; METAANALYSIS; COLONOSCOPY; MANAGEMENT; DIAGNOSIS; DISEASE AB Multiple procedures and medical devices are being used in a complex interplay to diagnose and treat gastrointestinal bleeding. The aim of the study was to develop a mathematical model that helps in estimating the average number of procedures to be expected in the general management of gastrointestinal bleeding. The modeling process serves as an example of how mathematical analysis in general can be used to answer unresolved clinical questions, lead to a better understanding of the underlying influences in a disease process, and provide a starting point for future clinical trials. The analysis uses a Markov chain to model the transition probabilities among consecutive interventions used to find and treat a bleeding site. The results show that starting a work-up of gastrointestinal bleeding with an esophagogastroduodenoscopy will lead on average to 2.69 procedures per patient. Of these expected procedures, 1.46 will be esophagogastroduodenoscopies, 0.69 colonoscopies, 0.25 video capsule endoscopies, 0.14 double-balloon enteroscopies, and 0.14 procedures from interventional radiology. Management chains initiated with a colonoscopy result in similar outcomes. Among 10,000 simulated individual patients, the number of procedures varies between 1 and 16 consecutive procedures, with 95% of all patients undergoing 6 procedures or less. The outcomes of the model suggest that the published success rates of endoscopic and radiographic procedures are overly optimistic. The results also point to the need to generate clinical data through future studies that more reliably account for treatment failures and the interchange among various complementary diagnostic modalities. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 29 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 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2015 VL 13 IS 3 BP 433 EP 439 DI 10.1016/j.cgh.2014.01.019 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CB6RJ UT WOS:000349754000011 PM 24440338 ER PT J AU Berry, K Taylor, J Liou, IW Ioannou, GN AF Berry, Kristin Taylor, Justin Liou, Iris W. Ioannou, George N. TI Portal Vein Thrombosis Is Not Associated With Increased Mortality Among Patients With Cirrhosis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Portal Vein Thrombosis; Cirrhosis; Mortality; Liver Transplantation; UNOS; Survival; MELD ID LIVER; SURVIVAL; ANTICOAGULATION; OUTCOMES AB BACKGROUND & AIMS: Portal vein thrombosis (PVT) is common in patients with cirrhosis and may have adverse clinical consequences. We investigated whether PVT is associated with survival in patients with cirrhosis. METHODS: Using the United Network for Organ Sharing registries from 2002 through 2013, we followed a cohort of transplant-naive adults with cirrhosis without hepatocellular carcinoma (N = 66,506) from the time of transplant listing until the time of liver transplantation or death before transplantation. We used Cox proportional hazards analysis and competing risks analysis to compare patients who had PVT at the time of listing (n = 2207) with those who did not (n = 64,299) with regard to the risk of transplantation or death before transplantation, after adjusting for important baseline characteristics. RESULTS: During a mean follow-up period of 1.78 years, 17,757 (27%) patients died before liver transplantation, 29,179 (44%) patients underwent transplantation, and 19,570 (29%) patients were still alive without having undergone transplantation. Compared with patients who did not have PVT, patients with PVT had lower mortality (adjusted hazard ratio [AHR], 0.88; 95% confidence interval [CI], 0.81-0.96), a similar risk of transplantation (AHR, 0.95; 95% CI, 0.89-1.02), and a lower risk of the combined outcome of death or transplantation (AHR, 0.95; 95% CI, 0.88-0.97). Similar results were found by competing risks analyses. Independent predictors of mortality included age, model for end-stage liver disease score, serum albumin level, ascites, encephalopathy, diabetes, hepatitis C virus infection, and low body mass index (<24.4 kg/m(2)). CONCLUSIONS: Among patients with cirrhosis on liver transplant waiting lists, patients with PVT have lower mortality than patients without PVT. C1 [Berry, Kristin; Ioannou, George N.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. [Taylor, Justin; Liou, Iris W.; Ioannou, George N.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, S-111-Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Health Resources and Services Administration [231-00-0115] FX Supported in part by Health Resources and Services Administration contract 231-00-0115. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services. NR 18 TC 12 Z9 13 U1 0 U2 4 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 MAR PY 2015 VL 13 IS 3 BP 585 EP 593 DI 10.1016/j.cgh.2014.10.010 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CB6RJ UT WOS:000349754000031 PM 25459555 ER PT J AU Herbrecht, R Patterson, TF Slavin, MA Marchetti, O Maertens, J Johnson, EM Schlamm, HT Donnelly, JP Pappas, PG AF Herbrecht, Raoul Patterson, Thomas F. Slavin, Monica A. Marchetti, Oscar Maertens, Johan Johnson, Elizabeth M. Schlamm, Haran T. Donnelly, J. Peter Pappas, Peter G. TI Application of the 2008 Definitions for Invasive Fungal Diseases to the Trial Comparing Voriconazole Versus Amphotericin B for Therapy of Invasive Aspergillosis: A Collaborative Study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE voriconazole; amphotericin B; neutropenia; allogeneic hematopoietic stem cell transplantation; preemptive therapy ID RANDOMIZED-TRIAL; 1ST-LINE THERAPY; DIAGNOSIS; CASPOFUNGIN; CONSENSUS AB Background. Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions. Methods. The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged. Results. Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA. Conclusions. Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA. C1 [Herbrecht, Raoul] Hop Hautepierre, Dept Hematol & Oncol, Strasbourg, France. [Herbrecht, Raoul] Univ Strasbourg, F-67098 Strasbourg, France. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Slavin, Monica A.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Slavin, Monica A.] Univ Melbourne, Melbourne, Vic 3010, Australia. [Marchetti, Oscar] Lausanne Univ Hosp CHUV, Dept Med, Infect Dis Serv, Lausanne, Switzerland. [Maertens, Johan] Katholieke Univ Leuven, Univ Ziekenhuizen Leuven, Louvain, Belgium. [Johnson, Elizabeth M.] Publ Hlth England Mycol Reference Lab, Bristol, Avon, England. [Johnson, Elizabeth M.] Natl Collect Pathogen Fungi, Bristol, Avon, England. [Schlamm, Haran T.] Pfizer Global Res & Dev, New York, NY USA. [Donnelly, J. Peter] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Pappas, Peter G.] Univ Alabama Birmingham, Div Infect Dis, Dept Med, Birmingham, AL USA. RP Herbrecht, R (reprint author), Univ Strasbourg, Hop Hautepierre, Dept Hematol & Oncol, F-67098 Strasbourg, France. EM raoul.herbrecht@chru-strasbourg.fr OI Herbrecht, Raoul/0000-0002-9381-4876 FU Pfizer Inc. FX The Global Comparative Aspergillosis Study and this recategorization study were sponsored by Pfizer Inc. NR 15 TC 13 Z9 14 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 1 PY 2015 VL 60 IS 5 BP 713 EP 720 DI 10.1093/cid/ciu911 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CB6VY UT WOS:000349766100008 PM 25414266 ER PT J AU Westover, MB Shafi, MM Bianchi, MT Moura, LMVR O'Rourke, D Rosenthal, ES Chu, CJ Donovan, S Hoch, DB Kilbride, RD Cole, AJ Cash, SS AF Westover, M. Brandon Shafi, Mouhsin M. Bianchi, Matt T. Moura, Lidia M. V. R. O'Rourke, Deirdre Rosenthal, Eric S. Chu, Catherine J. Donovan, Samantha Hoch, Daniel B. Kilbride, Ronan D. Cole, Andrew J. Cash, Sydney S. TI The probability of seizures during EEG monitoring in critically ill adults SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Continuous electroencephalography; ICU EEG monitoring; Nonconvulsive seizures ID NONCONVULSIVE STATUS EPILEPTICUS; TRAUMATIC BRAIN-INJURY; INTENSIVE-CARE-UNIT; INTRACEREBRAL HEMORRHAGE; SUBARACHNOID HEMORRHAGE; ELECTROGRAPHIC SEIZURES; DISCHARGES; FREQUENCY; IMPACT AB Objective: To characterize the risk for seizures over time in relation to EEG findings in hospitalized adults undergoing continuous EEG monitoring (cEEG). Methods: Retrospective analysis of cEEG data and medical records from 625 consecutive adult inpatients monitored at a tertiary medical center. Using survival analysis methods, we estimated the time-dependent probability that a seizure will occur within the next 72-h, if no seizure has occurred yet, as a function of EEG abnormalities detected so far. Results: Seizures occurred in 27% (168/625). The first seizure occurred early (< 30 min of monitoring) in 58% (98/168). In 527 patients without early seizures, 159 (30%) had early epileptiform abnormalities, versus 368 (70%) without. Seizures were eventually detected in 25% of patients with early epileptiform discharges, versus 8% without early discharges. The 72-h risk of seizures declined below 5% if no epileptiform abnormalities were present in the first two hours, whereas 16 h of monitoring were required when epileptiform discharges were present. 20% (74/388) of patients without early epileptiform abnormalities later developed them; 23% (17/74) of these ultimately had seizures. Only 4% (12/294) experienced a seizure without preceding epileptiform abnormalities. Conclusions: Seizure risk in acute neurological illness decays rapidly, at a rate dependent on abnormalities detected early during monitoring. This study demonstrates that substantial risk stratification is possible based on early EEG abnormalities. Significance: These findings have implications for patient-specific determination of the required duration of cEEG monitoring in hospitalized patients. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Westover, M. Brandon; Shafi, Mouhsin M.; Bianchi, Matt T.; Moura, Lidia M. V. R.; O'Rourke, Deirdre; Rosenthal, Eric S.; Chu, Catherine J.; Donovan, Samantha; Hoch, Daniel B.; Kilbride, Ronan D.; Cole, Andrew J.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, Boston, MA 02114 USA. [Shafi, Mouhsin M.] Beth Israel Deaconess Med Ctr, Epilepsy Serv, Dept Neurol, Boston, MA 02214 USA. RP Westover, MB (reprint author), Massachusetts Gen Hosp, Wang 7 Neurol,55 Fruit St, Boston, MA 02114 USA. EM mwestover@mgh.harvard.edu; mshafi@bidmc.harvard.edu; mtbianchi@mgh.harvard.edu; lmoura@mgh.harvard.edu; daorourke@mgh.harvard.edu; erosenthal@mgh.harvard.edu; cchu3@mgh.harvard.edu; dbhoch@mgh.harvard.edu; rkilbride@mgh.harvard.edu; acole1@mgh.harvard.edu; scash@mgh.harvard.edu OI Hoch, Daniel/0000-0002-4294-024X; Rosenthal, Eric/0000-0003-3900-356X FU NINDS NIH HHS [K12 NS066225] NR 41 TC 6 Z9 7 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAR PY 2015 VL 126 IS 3 BP 463 EP 471 DI 10.1016/j.clinph.2014.05.037 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CB4RX UT WOS:000349616700008 PM 25082090 ER PT J AU Cronin, J Francis, J AF Cronin, Julie Francis, Jacquelyn TI Investigating the Use of Instructional Videos on Social Media to Increase Effectiveness of Hands-on Practical Applications SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Cronin, Julie; Francis, Jacquelyn] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0887-6274 EI 1538-9782 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2015 VL 29 IS 2 BP E50 EP E50 PG 1 WC Nursing SC Nursing GA CB3XT UT WOS:000349563500118 ER PT J AU Kekre, N Koreth, J AF Kekre, Natasha Koreth, John TI Novel strategies to prevent relapse after allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia and myelodysplastic syndromes SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE acute myeloid leukaemia; myelodysplastic syndromes; relapse; transplantation ID ACUTE MYELOGENOUS LEUKEMIA; DONOR LYMPHOCYTE INFUSION; MINIMAL RESIDUAL DISEASE; NATURAL-KILLER-CELLS; BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; REDUCED-INTENSITY; COMPLETE REMISSION; IN-VIVO; PHASE-I AB Purpose of reviewRelapse of haematological neoplasms after allogeneic haematopoietic stem cell transplantation (HSCT) remains one of the leading causes of death. Treatment of relapse post-HSCT is frequently ineffective and outcomes are poor, necessitating preventive strategies that are reviewed below.Recent findingsCurrent strategies to prevent relapse after HSCT are geared towards four general principles: improving the antitumour effects of conditioning regimens prior to HSCT, improving graft selection and engineering to augment the graft-versus-leukaemia effect, post-HSCT chemotherapeutic interventions to impair growth of residual clonal cells and post-HSCT immune-mediated interventions to enhance the graft-versus-leukaemia effect. Strategies based on cell manipulation, namely natural killer (NK) cell enrichment and adoptive T cell transfer, are emerging. Targeted therapies including vaccinations, FLT3 inhibitors, mAbs and chimeric antigen receptor T cell therapy represent a new avenue of treating acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Studies are underway to incorporate all of these strategies in the clinical setting to determine their impact on relapse and survival after HSCT.SummaryThe most recent evidence suggests that strategies using NK cell therapy and targeted immune therapies after HSCT may change the current landscape of HSCT for AML and MDS. C1 [Kekre, Natasha; Koreth, John] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. RP Koreth, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA. EM john_koreth@dfci.harvard.edu NR 52 TC 7 Z9 7 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2015 VL 22 IS 2 BP 116 EP 122 DI 10.1097/MOH.0000000000000116 PG 7 WC Hematology SC Hematology GA CB1JR UT WOS:000349384000007 PM 25575033 ER PT J AU Wolach, O Stone, RM AF Wolach, Ofir Stone, Richard M. TI Is it time to change conventional consolidation chemotherapy for acute myeloid leukemia in CR1? SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE acute myeloid leukemia; allogeneic stem cell transplant; first remission; postremission therapy ID CORE-BINDING-FACTOR; STEM-CELL TRANSPLANTATION; 1ST COMPLETE REMISSION; ACUTE MYELOGENOUS LEUKEMIA; HIGH-DOSE CYTARABINE; BONE-MARROW-TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; INTERNAL TANDEM DUPLICATION; INDIVIDUAL PATIENT DATA; FRENCH AML INTERGROUP AB Purpose of reviewChoosing the most appropriate postremission therapy (PRT) for a patient with acute myeloid leukemia (AML) in first complete remission remains a challenging task. Factors such as risk for disease relapse, nonrelapse mortality associated with different PRT approaches, donor availability, prospects for salvage should disease relapse, and patient preference all affect PRT choice.Recent findingsNew genetic markers refine AML risk stratification and identify patients within the classical' risk groups who may benefit from transplant-based or chemotherapy-based PRT. The use of minimal residual disease in first remission to guide PRT choice and the application of novel, targeted therapies have the potential to alter PRT approaches across AML risk groups. The advent of alternative donor sources, use of reduced intensity regimens, and improved supportive care all affect the availability and safety of transplant-based PRT and challenge the relevance of the older legacy donor/no-donor' genetically randomized trials.SummaryGenetic risk assessment, monitoring of minimal residual disease in first remission, use of targeted agents, and the newer transplant strategies all have the potential to personalize' PRT choice in the AML patient. The clinical value of these novel interventions awaits validation in prospective, risk-adapted clinical trials. C1 [Wolach, Ofir; Stone, Richard M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM rstone@partners.org NR 94 TC 3 Z9 3 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2015 VL 22 IS 2 BP 123 EP 131 DI 10.1097/MOH.0000000000000119 PG 9 WC Hematology SC Hematology GA CB1JR UT WOS:000349384000008 PM 25594168 ER PT J AU Padron, E Steensma, DP AF Padron, Eric Steensma, David P. TI Cutting the cord from myelodysplastic syndromes: chronic myelomonocytic leukemia-specific biology and management strategies SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE chronic leukemias; chronic myelomonocytic leukemia; myelodysplastic syndromes; myelodysplastic syndrome; myeloproliferative neoplasm overlap disorders; somatic mutations ID PROGNOSTIC SCORING SYSTEM; WORLD-HEALTH-ORGANIZATION; ACUTE MYELOID-LEUKEMIA; RISK STRATIFICATION; MUTATIONS; AZACITIDINE; ABNORMALITIES; DECITABINE; CYTARABINE; DISORDERS AB Purpose of reviewChronic myelomonocytic leukemia (CMML) is a troublesome hematologic malignancy characterized by peripheral blood monocytosis, marrow dysplasia, cytopenias, frequent extramedullary involvement by clonal cells, and a propensity for progression to acute myeloid leukemia. Although previously considered a subtype of the myelodysplastic syndromes (MDS), CMML is now recognized as a distinct entity with unique biologic and clinical features. This change has created a scientific and clinical research landscape that makes it difficult to discern CMML-specific validated conclusions versus speculative extrapolation from more general MDS data.Recent findingsHere, we review recent biologic observations that support the current CMML WHO classification, such as the high frequency of SRSF2 and ASXL1 mutations compared with MDS and critical dependence of CMML cells on granulocyte-macrophage colony-stimulating factor signaling. In addition, we discuss CMML-specific prognostic tools and therapeutic results of agents developed for MDS in patients with CMML.SummaryThe present review focuses on evidence supporting CMML ontology and identifies key clinical differences in the management of CMML and that of MDS subtypes. C1 [Padron, Eric] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Steensma, DP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Dana 2037, Boston, MA 02215 USA. EM david_steensma@dfci.harvard.edu FU Evans Foundation; American Society of Hematology; Incyte; Cell Therapeutics; FORMA FX E.P. has received honoraria from Incyte and Novartis. E.P. is currently receiving a grant from the Evans Foundation, American Society of Hematology, Incyte, Cell Therapeutics, and FORMA. The remaining authors have no conflicts of interest. NR 44 TC 4 Z9 4 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2015 VL 22 IS 2 BP 163 EP 170 DI 10.1097/MOH.0000000000000112 PG 8 WC Hematology SC Hematology GA CB1JR UT WOS:000349384000013 PM 25575034 ER PT J AU Hobbs, GS Rampal, RK AF Hobbs, Gabriela S. Rampal, Raajit K. TI Clinical and molecular genetic characterization of myelofibrosis SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE genetics; myelofibrosis; ruxolitinib ID CHRONIC MYELOMONOCYTIC LEUKEMIA; INTERNATIONAL WORKING GROUP; PHASE MYELOPROLIFERATIVE NEOPLASMS; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; MYELOID METAPLASIA; SOMATIC MUTATIONS; ASXL1 MUTATIONS; MYELODYSPLASTIC SYNDROMES AB Purpose of reviewThe myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and myelofibrosis. Of these, myelofibrosis often has the most aggressive course. There is, however, often significant clinical heterogeneity among patients with myelofibrosis. We seek to summarize recent clinical and biological findings in myelofibrosis as well as review the spectrum of clinically relevant mutation in myelofibrosis and their implications.Recent findingsThe mutational spectrum in myelofibrosis includes driver mutations in genes such as JAK2, calreticulin, and myeloproliferative leukemia virus oncogene. In addition, recurrent mutations in epigenetic modifiers such as ASXL1 and TET2 have also been described. Importantly, several studies have indicated that specific mutations, as well as the number of mutations, that a patient bears may have important clinical consequences. The presence or absence of certain mutations may help to determine a patient's risk for thrombosis, leukemic transformation, and survival.SummaryMyelofibrosis often has variable outcomes among patients. Prognostic systems based on clinical observations have been developed in an attempt to predict risks of disease progression and transformation. The discovery of recurrent genomic alterations in myelofibrosis, and the observation that many of these alterations may help predict clinical outcomes, has heralded a new era in the biologic understanding and clinical approach to myelofibrosis. C1 [Hobbs, Gabriela S.] Massachusetts Gen Hosp, Leukemia Serv, Boston, MA 02114 USA. [Rampal, Raajit K.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10021 USA. RP Rampal, RK (reprint author), 1275 York Ave, New York, NY 10065 USA. EM rampalr@mskcc.org OI Hobbs, Gabriela/0000-0002-0199-9333 NR 66 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 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2015 VL 22 IS 2 BP 177 EP 183 DI 10.1097/MOH.0000000000000122 PG 7 WC Hematology SC Hematology GA CB1JR UT WOS:000349384000015 PM 25635755 ER PT J AU Sircar, M Thadhani, R Karumanchi, SA AF Sircar, Monica Thadhani, Ravi Karumanchi, S. Ananth TI Pathogenesis of preeclampsia SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE angiogenic factors; placental growth factor; preeclampsia; pregnancy; proteinuria; soluble fms-like tyrosine kinase 1; vascular endothelial growth factor ID ENDOTHELIAL-GROWTH-FACTOR; TYROSINE KINASE 1; SUSPECTED PREECLAMPSIA; CARDIOVASCULAR-DISEASE; ANTIANGIOGENIC FACTORS; ANGIOGENIC FACTORS; FACTOR RECEPTOR-1; SOLUBLE ENDOGLIN; GESTATIONAL HYPERTENSION; AGONISTIC AUTOANTIBODIES AB Purpose of reviewPreeclampsia is a gestational kidney disease characterized by glomerular endothelial injury, leading to maternal hypertension and proteinuria. If not addressed promptly, there is significant maternal and fetal morbidity and mortality. When severe, this disorder can cause hepatic and neurologic dysfunction. Understandably, this placental disease enters the focus of the obstetrician first; however, with progression, the nephrologist can also be enlisted. Typical complications include acute kidney injury, refractory hypertension, and acute pulmonary edema. This review summarizes recent literature on the pathogenesis of this condition and will highlight new diagnostic and therapeutic options for preeclampsia.Recent findingsOver the past decade, the role of soluble vascular factors in preeclampsia has shed light on the mechanism underlying this disease. During the last 2 years, several new therapeutics have been developed that target implicated circulating angiogenic factors, including soluble fms-like tyrosine kinase 1, an endogenous vascular endothelial growth factor inhibitor. Serum levels of angiogenic factors have been correlated with a constellation of hemodynamic and pathophysiologic changes. Thus, circulating levels of these factors may serve both diagnostic and prognostic purposes.SummaryOverall, our understanding of preeclampsia has developed significantly and the future holds promise for mechanism-based novel diagnostics and therapeutics. C1 [Sircar, Monica; Thadhani, Ravi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sircar, Monica; Thadhani, Ravi; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,RN 370D, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu FU NIH FX M.S. is supported by NIH T32 award, R.T. by NIH K24 award, and S.A.K. is an investigator of the Howard Hughes Medical Institute. NR 75 TC 16 Z9 19 U1 1 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1062-4821 EI 1473-6543 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAR PY 2015 VL 24 IS 2 BP 131 EP 138 DI 10.1097/MNH.0000000000000105 PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA CB1JW UT WOS:000349384500004 PM 25636145 ER PT J AU Verloes, A Di Donato, N Masliah-Planchon, J Jongmans, M Abdul-Raman, OA Albrecht, B Allanson, J Brunner, H Bertola, D Chassaing, N David, A Devriendt, K Eftekhari, P Drouin-Garraud, V Faravelli, F Faivre, L Giuliano, F Almeida, LG Juncos, J Kempers, M Eker, HK Lacombe, D Lin, A Mancini, G Melis, D Lourenco, CM Siu, VM Morin, G Nezarati, M Nowaczyk, MJM Ramer, JC Osimani, S Philip, N Pierpont, ME Procaccio, V Roseli, ZS Rossi, M Rusu, C Sznajer, Y Templin, L Uliana, V Klaus, M Van Bon, B Van Ravenswaaij, C Wainer, B Fry, AE Rump, A Hoischen, A Drunat, S Riviere, JB Dobyns, WB Pilz, DT AF Verloes, Alain Di Donato, Nataliya Masliah-Planchon, Julien Jongmans, Marjolijn Abdul-Raman, Omar A. Albrecht, Beate Allanson, Judith Brunner, Han Bertola, Debora Chassaing, Nicolas David, Albert Devriendt, Koen Eftekhari, Pirayeh Drouin-Garraud, Valerie Faravelli, Francesca Faivre, Laurence Giuliano, Fabienne Almeida, Leina Guion Juncos, Jorge Kempers, Marlies Eker, Hatice Kocak Lacombe, Didier Lin, Angela Mancini, Grazia Melis, Daniela Lourenco, Charles Marques Siu, Victoria Mok Morin, Gilles Nezarati, Marjan Nowaczyk, Malgorzata J. M. Ramer, Jeanette C. Osimani, Sara Philip, Nicole Pierpont, Mary Ella Procaccio, Vincent Roseli, Zeichi-Seide Rossi, Massimiliano Rusu, Cristina Sznajer, Yves Templin, Ludivine Uliana, Vera Klaus, Mirjam Van Bon, Bregje Van Ravenswaaij, Conny Wainer, Bruce Fry, Andrew E. Rump, Andreas Hoischen, Alexander Drunat, Severine Riviere, Jean-Baptiste Dobyns, William B. Pilz, Daniela T. TI Baraitser-Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID APPARENTLY UNDESCRIBED SYNDROME; BETA-ACTIN; MENTAL-RETARDATION; GAMMA-ACTIN; IRIS COLOBOMA; FUNCTIONAL DIVERSITY; GYRAL MALFORMATIONS; GROWTH-RETARDATION; FACIAL SYNDROME; SHALLOW ORBITS AB Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode beta-and gamma-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity. C1 [Verloes, Alain; Masliah-Planchon, Julien; Osimani, Sara; Drunat, Severine] Robert DEBRE Univ Hosp, APHP, Dept Genet, Paris, France. [Verloes, Alain; Masliah-Planchon, Julien; Osimani, Sara; Drunat, Severine] Paris Diderot Univ, Paris, France. [Verloes, Alain] Hosp Robert DEBRE, INSERM UMR 1141, Paris, France. [Di Donato, Nataliya; Rump, Andreas] Fac Med Carl Gustav Carus, Inst Clin Genet, Dresden, Germany. [Jongmans, Marjolijn; Brunner, Han; Kempers, Marlies; Van Bon, Bregje; Hoischen, Alexander] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. [Abdul-Raman, Omar A.] Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA. [Albrecht, Beate] Univ Klinikum Essen, Inst Humangenet, Essen, Germany. [Allanson, Judith] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. [Bertola, Debora] Univ Sao Paulo, Fac Med, Hosp Clin, Sao Paulo, Brazil. [Bertola, Debora] Univ Sao Paulo, Inst Biociencias, Sao Paulo, Brazil. [Chassaing, Nicolas] Purpan Univ Hosp, Serv Genet Med, Toulouse, France. [David, Albert] Univ Hosp, Serv Genet Med, Nantes, France. [Devriendt, Koen] Univ Hosp Gasthuisberg, Dept Genet, Leuven, Belgium. [Eftekhari, Pirayeh] Lariboisiere Hosp, APHP, Dept Hematol, Paris, France. [Drouin-Garraud, Valerie] Univ Hosp, Serv Genet Med, Rouen, France. [Faravelli, Francesca; Riviere, Jean-Baptiste] Osped Galliera, Dipartimento Genet Med, Genoa, Italy. [Faivre, Laurence] Univ Hosp, Serv Genet Med, Dijon, France. [Giuliano, Fabienne] Univ Hosp, Serv Genet Med, Nice, France. [Almeida, Leina Guion; Roseli, Zeichi-Seide] Univ Sao Paulo, Hosp Rehabil Craniofacial Anomalies HRAC, Dept Clin Genet, Bauru, Brazil. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Eker, Hatice Kocak] Dr Faruk Sukan Matern & Childrens Hosp, Dept Med Genet, Konya, Turkey. [Lacombe, Didier] Univ Hosp, Serv Genet Med, Bordeaux, France. [Lin, Angela] Massachusetts Gen Hosp, Med Genet Unit, Boston, MA 02114 USA. [Mancini, Grazia] Erasmus MC, Rotterdam, Netherlands. [Melis, Daniela] Univ Naples Federico II, Dipartimento Pediat, Naples, Italy. [Lourenco, Charles Marques] Univ Sao Paulo, Clin Hosp Ribeirao Preto, Sao Paulo, Brazil. [Siu, Victoria Mok] Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada. [Morin, Gilles] Univ Hosp, Serv Genet Med, Amiens, France. [Nezarati, Marjan] North York Gen Hosp, Toronto, ON, Canada. [Nowaczyk, Malgorzata J. M.] McMaster Univ, Hamilton, ON, Canada. [Ramer, Jeanette C.] Penn State Univ, Dept Pediat, Hershey, PA USA. [Philip, Nicole; Templin, Ludivine] La Timone Univ Hosp, Serv Genet Med, Marseille, France. [Pierpont, Mary Ella] Univ Minnesota, Med Ctr, Dept Pediat & Ophthalmol, Minneapolis, MN 55455 USA. [Procaccio, Vincent] Univ Hosp, Dept Genet, Angers, France. [Rossi, Massimiliano] Univ Hosp, Serv Genet Med, Lyon, France. [Rusu, Cristina] Univ Hosp, Dept Genet, Iasi, Romania. [Sznajer, Yves] St Luc Univ Hosp, Serv Genet Med, Brussels, Belgium. [Uliana, Vera] Osped Galliera, Dipartimento Genet Med, Genoa, Italy. [Klaus, Mirjam] Mitteldeutscher Praxisverbund Humangenet, Dresden, Germany. [Van Ravenswaaij, Conny] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Wainer, Bruce] Off Chief Med Examiner, San Francisco, CA USA. [Fry, Andrew E.; Pilz, Daniela T.] Univ Wales Hosp, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales. [Riviere, Jean-Baptiste; Dobyns, William B.] Seattle Childrens Hosp, Seattle, WA USA. RP Verloes, A (reprint author), CHU Robert DEBRE, Dept Genet, 48 Blvd SERURIER, F-75019 Paris, France. EM alain.verloes@rdb.aphp.fr RI Brunner, Han/C-9928-2013; Hoischen, Alexander/D-1282-2013; Procaccio, Vincent/M-2596-2015; van Bon, Bregje/Q-2445-2015; Philip, Nicole/I-2881-2016; Fapesp-Cepid, CEGH-CEL/J-3613-2015; OI Hoischen, Alexander/0000-0002-8072-4476; , Alain/0000-0003-4819-0264; Rump, Andreas/0000-0001-7116-6364; Dobyns, William/0000-0002-7681-2844 FU Baily Thomas Charitable Fund, UK; National Institute for Social Care and Health Research (NISCHR), Wales, UK FX We would like to thank all the patients and their families for their interest and participation. This work was supported by the Baily Thomas Charitable Fund, UK and the National Institute for Social Care and Health Research (NISCHR), Wales, UK. NR 51 TC 10 Z9 10 U1 3 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAR PY 2015 VL 23 IS 3 BP 292 EP 301 DI 10.1038/ejhg.2014.95 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CB5MG UT WOS:000349670900004 PM 25052316 ER PT J AU Kreiner-Moller, E Medina-Gomez, C Uitterlinden, AG Rivadeneira, F Estrada, K AF Kreiner-Moller, Eskil Medina-Gomez, Carolina Uitterlinden, Andre G. Rivadeneira, Fernando Estrada, Karol TI Improving accuracy of rare variant imputation with a two-step imputation approach SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GENOTYPE IMPUTATION AB Genotype imputation has been the pillar of the success of genome-wide association studies (GWAS) for identifying common variants associated with common diseases. However, most GWAS have been run using only 60 HapMap samples as reference for imputation, meaning less frequent and rare variants not being comprehensively scrutinized. Next-generation arrays ensuring sufficient coverage together with new reference panels, as the 1000 Genomes panel, are emerging to facilitate imputation of low frequent single-nucleotide polymorphisms (minor allele frequency (MAF) <5%). In this study, we present a two-step imputation approach improving the quality of the 1000 Genomes imputation by genotyping only a subset of samples to create a local reference population on a dense array with many low-frequency markers. In this approach, the study sample, genotyped with a first generation array, is imputed first to the local reference sample genotyped on a dense array and hereafter to the 1000 Genomes reference panel. We show that mean imputation quality, measured by the r(2) using this approach, increases by 28% for variants with a MAF between 1 and 5% as compared with direct imputation to 1000 Genomes reference. Similarly, the concordance rate between calls of imputed and true genotypes was found to be significantly higher for heterozygotes (P<1e-15) and rare homozygote calls (P<1e-15) in this low frequency range. The two-step approach in our setting improves imputation quality compared with traditional direct imputation noteworthy in the low-frequency spectrum and is a cost-effective strategy in large epidemiological studies. C1 [Kreiner-Moller, Eskil; Medina-Gomez, Carolina; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol] Erasmus Univ, Med Ctr, Dept Internal Med, Genet Lab Internal Med, NL-3000 CA Rotterdam, Netherlands. [Kreiner-Moller, Eskil] Univ Copenhagen, Fac Hlth Sci, COPSAC, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark. [Kreiner-Moller, Eskil] Copenhagen Univ Hosp, Danish Pediat Asthma Ctr, Gentofte, Denmark. [Estrada, Karol] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Estrada, Karol] Harvard Univ, Sch Med, Boston, MA USA. [Estrada, Karol] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Estrada, K (reprint author), Erasmus Univ, Med Ctr, Dept Internal Med, Genet Lab Internal Med, POB 2040 Ee5-79, NL-3000 CA Rotterdam, Netherlands. EM karol@broadinstitute.org OI Rivadeneira, Fernando/0000-0001-9435-9441; Kreiner, Eskil/0000-0003-1204-2438; Medina-Gomez, Carolina/0000-0001-7999-5538 FU Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Netherlands Genomics Initiative; Ministry of Education, Culture and Science; Ministry of Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; European Respiratory Society [429-2011]; NWO Rubicon fellowship [825.12.023] FX The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research (NWO), The Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The contribution of inhabitants, general practitioners and pharmacists of the Ommoord district to the Rotterdam Study is gratefully acknowledged. We further acknowledge the support of the European Respiratory Society, Fellowship STRTF 429-2011 and from the NWO Rubicon fellowship 825.12.023. NR 15 TC 7 Z9 7 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAR PY 2015 VL 23 IS 3 BP 395 EP 400 DI 10.1038/ejhg.2014.91 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CB5MG UT WOS:000349670900019 PM 24939589 ER PT J AU Harte, CB Vujanovic, AA Potter, CM AF Harte, Christopher B. Vujanovic, Anka A. Potter, Carrie M. TI Association Between Exercise and Posttraumatic Stress Symptoms Among Trauma-Exposed Adults SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE posttraumatic stress; PTSD; trauma; exercise; physical activity ID ANXIETY SENSITIVITY; PHYSICAL-ACTIVITY; COLLEGE-STUDENTS; DISORDER AB The present investigation examined associations between intensities of exercise involvement and posttraumatic stress (PTS) symptom cluster severity (reexperiencing, avoidance/numbing, and hyperarousal). The sample was comprised of 108 adults (54.6% women; M-age = 23.9, SD = 10.22, range = 18-62), who endorsed exposure to a Diagnostic and Statistical Manual of Mental Disorders (Fourth edition, Text Revision) posttraumatic stress disorder Criterion A traumatic life event but did not meet criteria for any current Axis I psychopathology. After controlling for gender and lifetime number of trauma exposure types experienced, results indicated that vigorous-intensity exercise, but not light- or moderate-intensity exercise, was significantly inversely associated with hyperarousal symptom cluster severity. This study adds to the scarce, yet growing, body of exercisePTS literatureby illuminating the inverse associations of vigorous-intensity exercise, specifically, and PTS hyperarousal symptom severity among trauma-exposed individuals. C1 [Harte, Christopher B.] Boston Univ, VA Boston Healthcare Syst, Res Serv, Dept Psychiat,Sch Med, Boston, MA 02215 USA. [Vujanovic, Anka A.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77021 USA. [Potter, Carrie M.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. RP Vujanovic, AA (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Psychiat & Behav Sci, 2800 South MacGregor Way, Houston, TX 77021 USA. EM anka.a.vujanovic@uth.tmc.edu OI Harte, Christopher/0000-0002-8097-7369 FU National Research Service Award [1 F31 DA021006-02] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported, in part, by a National Research Service Award (1 F31 DA021006-02) granted to Anka Vujanovic. NR 19 TC 1 Z9 1 U1 4 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 EI 1552-3918 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD MAR PY 2015 VL 38 IS 1 BP 42 EP 52 DI 10.1177/0163278713494774 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CB5SF UT WOS:000349687100004 PM 23864542 ER PT J AU Delaney, CB Eddy, KT Hartmann, AS Becker, AE Murray, HB Thomas, JJ AF Delaney, Charlotte B. Eddy, Kamryn T. Hartmann, Andrea S. Becker, Anne E. Murray, Helen B. Thomas, Jennifer J. TI Pica and Rumination Behavior among Individuals Seeking Treatment for Eating Disorders or Obesity SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE pica; rumination; DSM-5; eating disorder; feeding disorder ID BULIMIA-NERVOSA; CHILDREN; ADOLESCENTS; PAGOPHAGIA; DIAGNOSIS; IRON AB ObjectivePica and rumination disorder (RD)formerly classified within DSM-IV Feeding and Eating Disorders of Infancy or Early Childhoodare now classified within DSM-5 Feeding and Eating Disorders. Though pica and RD have been studied in select populations (e.g., pregnant women, intellectually disabled persons), their typical features and overall prevalence remain unknown. This study examined the clinical characteristics and frequency of DSM-5 pica and RD among individuals seeking treatment for eating disorders and obesity. MethodWe conducted structured interviews with adolescent and young adult females from a residential eating disorder center (N=149), and adult males and females with overweight or obesity from an outpatient weight-loss clinic (N=100). ResultsSeveral participants reported ingesting non-nutritive substances (e.g., ice) for weight-control purposes. However, only 1.3% (n=2; 95% CI: .06% to 5.1%) at the residential eating disorder center and 0% at the weight-loss clinic met DSM-5 criteria for pica, consuming gum and plastic. Although no eating disorder participants were eligible for an RD diagnosis due to DSM-5 trumping rules, 7.4% (n=11; 95% CI: 4.0% to 12.9%) endorsed rumination behavior under varying degrees of volitional control. At the weight-loss clinic, 2.0% (n=2; 95% CI: 0.1% to 7.4%) had RD. DiscussionDSM-5 pica and RD were rare in our sample of individuals seeking treatment for eating disorders and obesity, but related behaviors were more common. The wide range of pica and rumination presentations highlights the challenges of differential diagnosis with other forms of disordered eating. (c) 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:238-248) C1 [Delaney, Charlotte B.] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA. [Delaney, Charlotte B.; Eddy, Kamryn T.; Becker, Anne E.; Murray, Helen B.; Thomas, Jennifer J.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Eddy, Kamryn T.; Becker, Anne E.; Thomas, Jennifer J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Hartmann, Andrea S.] Univ Osnabruck, Insititute Psychol, D-49069 Osnabruck, Germany. [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. RP Thomas, JJ (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. EM jjthomas@mgh.harvard.edu FU Office of Medical Student Research of the Albert Einstein College of Medicine; Hilda and Preston Davis Foundation FX Supported by Office of Medical Student Research of the Albert Einstein College of Medicine and Hilda and Preston Davis Foundation. NR 32 TC 2 Z9 2 U1 7 U2 31 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 MAR PY 2015 VL 48 IS 2 BP 238 EP 248 DI 10.1002/eat.22279 PG 11 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA CB4ME UT WOS:000349601100010 PM 24729045 ER PT J AU Applebaum, AJ Bedoya, CA Hendriksen, ES Wilkinson, JL Safren, SA O'Cleirigh, C AF Applebaum, Allison J. Bedoya, C. Andres Hendriksen, Ellen S. Wilkinson, Jesse L. Safren, Steven A. O'Cleirigh, Conall TI Future Directions for Interventions Targeting PTSD in HIV-infected Adults SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE HIV; intervention development; posttraumatic stress disorder (PTSD); research recommendations ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; HUMAN-IMMUNODEFICIENCY-VIRUS; WRITTEN EMOTIONAL DISCLOSURE; RANDOMIZED CONTROLLED-TRIALS; SUBSTANCE USE DISORDERS; COPING INTERVENTION; PROLONGED EXPOSURE; TRAUMATIC STRESS; HEALTH OUTCOMES AB Although studies consistently report high rates of comorbid posttraumatic stress disorder (PTSD) and HIV infection, development and testing of PTSD treatment interventions in HIV-infected adults is limited. As such, the purpose of this review was twofold. First, this review augments the three existing reviews of research for PTSD in HIV-infected adults conducted within the past 10 years. We found two empirically supported cognitive-behavioral therapy-based interventions for the treatment of trauma-related symptoms in HIV-infected adults. Due to the continued limited number of effective interventions for this population, a second aim of our review was to draw from the expansive field of effective PTSD interventions for the general population to propose ways that future clinical intervention research may be tailored for HIV-infected adults. Therefore, in addition to a review, we conceptualized this paper as an opportunity to generate an ideal preview of the field of intervention research in this population. Copyright (C) 2015 Association of Nurses in AIDS Care C1 [Applebaum, Allison J.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [Bedoya, C. Andres; Safren, Steven A.; O'Cleirigh, Conall] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bedoya, C. Andres; Safren, Steven A.; O'Cleirigh, Conall] Harvard Univ, Sch Med, Boston, MA USA. [Hendriksen, Ellen S.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Wilkinson, Jesse L.] SUNY Stony Brook, Dept Clin Psychol, Stony Brook, NY 11794 USA. RP Applebaum, AJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 1275 York Ave, New York, NY 10021 USA. FU National Institute of Mental Health [MH094214, MH084757]; Harvard University Center for AIDS Research by National Institute of Allergy and Infectious Diseases [P30AI060354] FX Funding note: Some of the authors time was supported by grants MH094214 (Safren) and MH084757 (Safren) funded by the National Institute of Mental Health, and P30AI060354 (Walker) from the Harvard University Center for AIDS Research funded by the National Institute of Allergy and Infectious Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 69 TC 3 Z9 3 U1 0 U2 5 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 MAR-APR PY 2015 VL 26 IS 2 DI 10.1016/j.jana.2014.11.001 PG 12 WC Nursing SC Nursing GA CB4PC UT WOS:000349609100004 PM 25665885 ER PT J AU Machtinger, EL Lavin, SM Hilliard, S Jones, R Haberer, JE Capito, K Dawson-Rose, C AF Machtinger, Edward L. Lavin, Sonja M. Hilliard, Starr Jones, Rhodessa Haberer, Jessica E. Capito, Kristen Dawson-Rose, Carol TI An Expressive Therapy Group Disclosure Intervention for Women Living With HIV Improves Social Support, Self-efficacy, and the Safety and Quality of Relationships: A Qualitative Analysis SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE disclosure; expressive therapy; HIV; trauma; self-efficacy; women ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROCESSES MODEL; POSITIVE WOMEN; VIOLENCE; SAMPLE; INFECTION; ADHERENCE; HIV/AIDS; OUTCOMES; TRAUMA AB Women living with HIV (WLHIV) face high rates of morbidity and mortality. HIV disclosure interventions have been identified as a promising but under-evaluated approach for WLHIV to improve their health and well-being. The Medea Project is an expressive therapy group intervention that was first developed to help incarcerated women develop the confidence and skills to tell their stories publicly in theatrical performances. The intervention was subsequently adapted as a community-based disclosure intervention for WLHIV. Our study describes an analysis of the impact of the Medea Project on the lives of the WLHIV who participated. All participating WLHIV publicly disclosed their HIV status during the performances. Five impact themes emerged from the data: sisterhood, catharsis, self-acceptance, safer and healthier relationships, and gaining a voice. Our study identifies a voluntary, effective, and broadly beneficial disclosure intervention for women living with HIV. Copyright (C) 2015 The Authors. Published by Elsevier Inc. All rights reserved C1 [Machtinger, Edward L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lavin, Sonja M.; Dawson-Rose, Carol] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Hilliard, Starr; Capito, Kristen] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Jones, Rhodessa] Medea Project Theater Incarcerated Women, San Francisco, CA USA. [Haberer, Jessica E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Haberer, Jessica E.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. RP Machtinger, EL (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM Edward.machtinger@ucsf.edu NR 55 TC 2 Z9 3 U1 3 U2 11 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 MAR-APR PY 2015 VL 26 IS 2 DI 10.1016/j.jana.2014.05.001 PG 12 WC Nursing SC Nursing GA CB4PC UT WOS:000349609100009 PM 25027284 ER PT J AU Cutrona, SL Mazor, KM Vieux, SN Luger, TM Volkman, JE Rutten, LJF AF Cutrona, Sarah L. Mazor, Kathleen M. Vieux, Sana N. Luger, Tana M. Volkman, Julie E. Rutten, Lila J. Finney TI Health Information-Seeking on Behalf of Others: Characteristics of "Surrogate Seekers" SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Internet; Health information-seeking; Social network; Peer group; Caregiver ID ONLINE; BEHAVIOR AB Understanding the behaviors of surrogate seekers (those who seek health information for others) may guide efforts to improve health information transmission. We used 2011-2012 data from the Health Information National Trends Survey to describe behaviors of online surrogate seekers. Respondents were asked about use of the Internet for surrogate-seeking over the prior 12 months. Data were weighted to calculate population estimates. Two thirds (66.6 %) reported surrogate-seeking. Compared to those who sought health information online for only themselves, surrogate seekers were more likely to live in households with others (weighted percent 89.4 vs. 82.5 % of self-seekers; p < 0.05); no significant differences in sex, race, income or education were observed. Surrogate seekers were more likely to report activities requiring user-generated content: email communication with healthcare providers; visits to social networking sites to read and share about medical topics and participation in online health support groups. On multivariate analysis, those who had looked online for healthcare providers were more likely to be surrogate seekers (OR 1.67, 95 % CI 1.08-2.59). In addition to seeking health information, surrogate seekers create and pass along communications that may influence medical care decisions. Research is needed to identify ways to facilitate transmission of accurate health information. C1 [Cutrona, Sarah L.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Mazor, Kathleen M.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA 01605 USA. [Vieux, Sana N.] PCORI, Res Integrat & Evaluat Program, Washington, DC 20036 USA. [Luger, Tana M.] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA 01730 USA. [Volkman, Julie E.] US Dept Vet Affairs, ENR Mem Hosp, Bedford, MA USA. [Rutten, Lila J. Finney] Mayo Clin, Robert D & Patricia E Kern Ctr Sci Hlth Care Deli, Rochester, MN 55905 USA. RP Cutrona, SL (reprint author), Univ Massachusetts, Sch Med, 365 Plantat St,Biotech 1,Suite 100, Worcester, MA 01605 USA. EM sarah.cutrona@umassmemorial.org FU NCATS NIH HHS [KL2 TR000160] NR 20 TC 5 Z9 5 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 EI 1543-0154 J9 J CANCER EDUC JI J. Cancer Educ. PD MAR PY 2015 VL 30 IS 1 BP 12 EP 19 DI 10.1007/s13187-014-0701-3 PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA CB6TJ UT WOS:000349759300003 PM 24989816 ER PT J AU Sheppard, KD Ford, CR Sawyer, P Foley, KT Harada, CN Brown, CJ Ritchie, CS AF Sheppard, Kendra D. Ford, Channing R. Sawyer, Patricia Foley, Kathleen T. Harada, Caroline N. Brown, Cynthia J. Ritchie, Christine S. TI The interprofessional clinical experience: interprofessional education in the nursing home SO JOURNAL OF INTERPROFESSIONAL CARE LA English DT Article DE Health and social care; interprofessional education; interdisciplinary ID ATTITUDES; RESIDENTS; SCALE AB The interprofessional clinical experience (ICE) was designed to introduce trainees to the roles of different healthcare professionals, provide an opportunity to participate in an interprofessional team, and familiarize trainees with caring for older adults in the nursing home setting. Healthcare trainees from seven professions (dentistry, medicine, nursing, nutrition, occupational therapy, optometry and social work) participated in ICE. This program consisted of individual patient interviews followed by a team meeting to develop a comprehensive care plan. To evaluate the impact of ICE on attitudinal change, the UCLA Geriatric Attitudes Scale and a post-experience assessment were used. The post-experience assessment evaluated the trainees' perception of potential team members' roles and attitudes about interprofessional team care of the older adult. Attitudes toward interprofessional teamwork and the older adult were generally positive. ICE is a novel program that allows trainees across healthcare professions to experience interprofessional teamwork in the nursing home setting. C1 [Sheppard, Kendra D.; Ford, Channing R.; Sawyer, Patricia; Harada, Caroline N.; Brown, Cynthia J.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Dept Med, Birmingham, AL 35294 USA. [Foley, Kathleen T.] Brenau Univ North Atlanta Campus, Sch Occupat Therapy, Norcross, GA USA. [Harada, Caroline N.; Brown, Cynthia J.] GRECC, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Ritchie, Christine S.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Ritchie, Christine S.] Jewish Home San Francisco Ctr Res Aging, San Francisco, CA USA. RP Sheppard, KD (reprint author), Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Dept Med, 1720 2nd Ave South,CH19,218H, Birmingham, AL 35294 USA. EM ksheppard@uabmc.edu FU Health Resources and Services Administration (HRSA) [UB4HP19045]; Southeast Center of Excellence in Geriatric Medicine; VA Rehabilitation Research and Development Merit Review Award [E7036R]; Donald W. Reynolds Foundation; Geriatric Academic Leadership Award from the National Institute on Aging [1K07AG31779]; HRSA FX The authors received support for their individual roles in the Interprofessional Clinical Experience from the Health Resources and Services Administration (HRSA)-funded Geriatric Education Center Grant (UB4HP19045). K.D.S. received support as a John A. Hartford Foundation Scholar Award from the Southeast Center of Excellence in Geriatric Medicine. C.J.B. received support from the VA Rehabilitation Research and Development Merit Review Award (E7036R). C.N.H. received support from the Donald W. Reynolds Foundation. C.S.R is supported by a Geriatric Academic Leadership Award from the National Institute on Aging (1K07AG31779) and was previously supported by the HRSA-funded Geriatric Education Center grant while she was at the University of Alabama at Birmingham. K.T.F has no disclosures and no conflicts of interest. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding agencies. NR 7 TC 2 Z9 2 U1 1 U2 13 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1356-1820 EI 1469-9567 J9 J INTERPROF CARE JI J. Interprofessional Care PD MAR PY 2015 VL 29 IS 2 BP 170 EP 172 DI 10.3109/13561820.2014.942776 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CB5IP UT WOS:000349661000017 PM 25140581 ER PT J AU Imam, A Jin, G Sillesen, M Dekker, SE Bambakidis, T Hwabejire, JO Jepsen, CH Halaweish, I Alam, HB AF Imam, Ayesha Jin, Guang Sillesen, Martin Dekker, Simone E. Bambakidis, Ted Hwabejire, John O. Jepsen, Cecilie H. Halaweish, Ihab Alam, Hasan B. TI Fresh Frozen Plasma Resuscitation Provides Neuroprotection Compared to Normal Saline in a Large Animal Model of Traumatic Brain Injury and Polytrauma SO JOURNAL OF NEUROTRAUMA LA English DT Article DE hemorrhage; brain; trauma; resuscitation; plasma ID NITRIC-OXIDE; HEMORRHAGIC-SHOCK; FLUID RESUSCITATION; CEREBROSPINAL-FLUID; LYOPHILIZED PLASMA; MORTALITY; ENDOTHELIN-1; TRANSFUSION; MANAGEMENT; OUTCOMES AB We have previously shown that early treatment with fresh frozen plasma (FFP) is neuroprotective in a swine model of hemorrhagic shock (HS) and traumatic brain injury (TBI). However, it remains unknown whether this strategy would be beneficial in a more clinical polytrauma model. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, brain oxygenation, and intracranial pressure (ICP) and subjected to computer-controlled TBI and multi-system trauma (rib fracture, soft-tissue damage, and liver injury) as well as combined free and controlled hemorrhage (40% blood volume). After 2 h of shock (mean arterial pressure, 30-35 mm Hg), animals were resuscitated with normal saline (NS; 3xvolume) or FFP (1xvolume; n=6/group). Six hours postresuscitation, brains were harvested and lesion size and swelling were evaluated. Levels of endothelial-derived vasodilator endothelial nitric oxide synthase (eNOS) and vasoconstrictor endothelin-1 (ET-1) were also measured. FFP resuscitation was associated with reduced brain lesion size (1005.8 vs. 2081.9 mm(3); p=0.01) as well as swelling (11.5% vs. 19.4%; p=0.02). Further, FFP-resuscitated animals had higher brain oxygenation as well as cerebral perfusion pressures. Levels of cerebral eNOS were higher in the FFP-treated group (852.9 vs. 816.4 ng/mL; p=0.03), but no differences in brain levels of ET-1 were observed. Early administration of FFP is neuroprotective in a complex, large animal model of polytrauma, hemorrhage, and TBI. This is associated with a favorable brain oxygenation and cerebral perfusion pressure profile as well as higher levels of endothelial-derived vasodilator eNOS, compared to normal saline resuscitation. C1 [Imam, Ayesha; Sillesen, Martin; Hwabejire, John O.; Jepsen, Cecilie H.] Harvard Univ, Sch Med, Dept Surg,Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02115 USA. [Jin, Guang; Dekker, Simone E.; Bambakidis, Ted; Halaweish, Ihab; Alam, Hasan B.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Sillesen, Martin] Copenhagen Univ Hosp, Dept Surg, Hillerod, Denmark. [Dekker, Simone E.] Vrije Univ Amsterdam Med Ctr, Inst Cardiovasc Res, Dept Anesthesiol, Amsterdam, Netherlands. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu FU U.S. Army Medical Research and Materiel Command [GRANTT00521959] FX The study was funded by a grant from the U.S. Army Medical Research and Materiel Command (GRANTT00521959; to H.B.A.). NR 27 TC 4 Z9 4 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD MAR 1 PY 2015 VL 32 IS 5 BP 307 EP 313 DI 10.1089/neu.2014.3535 PG 7 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CC0SD UT WOS:000350045700003 PM 25153180 ER PT J AU Baugh, CM Kiernan, PT Kroshus, E Daneshvar, DH Montenigro, PH McKee, AC Stern, RA AF Baugh, Christine M. Kiernan, Patrick T. Kroshus, Emily Daneshvar, Daniel H. Montenigro, Philip H. McKee, Ann C. Stern, Robert A. TI Frequency of Head-Impact-Related Outcomes by Position in NCAA Division I Collegiate Football Players SO JOURNAL OF NEUROTRAUMA LA English DT Article DE American football; mild traumatic brain injury; concussion; college; linemen ID CHRONIC TRAUMATIC ENCEPHALOPATHY; HIGH-SCHOOL FOOTBALL; SPORT-RELATED CONCUSSION; STATES HIGH-SCHOOL; BRAIN-INJURY; PROFESSIONAL FOOTBALL; UNITED-STATES; SUBCONCUSSIVE IMPACTS; EPIDEMIOLOGY; INTERVENTION AB Concussions and subconcussive impacts sustained in American football have been associated with short- and long-term neurological impairment, but differences in head impact outcomes across playing positions are not well understood. The American Medical Society for Sports Medicine has identified playing position as a key risk factor for concussion in football and one for which additional research is needed. This study examined variation in head impact outcomes across primary football playing positions in a group of 730 National Collegiate Athletic Association Division I Football Championship Series athletes, using a self-report questionnaire. Although there were no significant differences between position groups in the number of diagnosed concussions during the 2012 football season, there were significant differences between groups in undiagnosed concussions (p=0.008) and "dings" (p<0.001); offensive linemen reported significantly higher numbers than most other positions. Significant differences were found between position groups in the frequencies of several postimpact symptoms, including dizziness (p<0.001), headache (p<0.001), and seeing stars (p<0.001) during the 2012 football season, with offensive linemen reporting significantly more symptoms compared to most other groups. There were also positional differences in frequency of returning to play while symptomatic (p<0.001) and frequency of participating in full-contact practice (p<0.001). Offensive linemen reported having returned to play while experiencing symptoms more frequently and participating in more full-contact practices than other groups. These findings suggest that offensive linemen, a position group that experiences frequent, but low-magnitude, head impacts, develop more postimpact symptoms than other playing positions, but do not report these symptoms as a concussion. C1 [Baugh, Christine M.] Harvard Univ, Harvard Interfac Initiat Hlth Policy, Cambridge, MA 02138 USA. [Baugh, Christine M.] Harvard Univ, Edmond J Safra Ctr Eth, Cambridge, MA 02138 USA. [Baugh, Christine M.] Boston Childrens Hosp, Div Sports Med, Boston, MA USA. [Kiernan, Patrick T.; Daneshvar, Daniel H.; Montenigro, Philip H.; McKee, Ann C.; Stern, Robert A.] Boston Univ, Chron Traumat Encephalopathy Ctr, Boston, MA 02215 USA. [Kroshus, Emily] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Kroshus, Emily] Natl Collegiate Athlet Assoc, Sport Sci Inst, Indianapolis, IN USA. [Daneshvar, Daniel H.] Boston Univ, Sch Med, Dept Behav Neurosci, Boston, MA 02118 USA. [Montenigro, Philip H.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [McKee, Ann C.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Stern, Robert A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Stern, Robert A.] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02118 USA. [Daneshvar, Daniel H.] Sports Legacy Inst, Boston, MA USA. [McKee, Ann C.] VA Boston Healthcare Syst, Boston, MA USA. [McKee, Ann C.; Stern, Robert A.] Boston Univ, Alzheimers Dis Ctr, Boston, MA 02215 USA. RP Baugh, CM (reprint author), Harvard Univ, Harvard Interfac Initiat Hlth Policy, 14 Story St,4th Floor, Cambridge, MA 02138 USA. EM cbaugh@g.harvard.edu OI Daneshvar, Daniel/0000-0003-3691-9513; Stern, Robert/0000-0002-5008-077X; Montenigro, Philip/0000-0003-4442-9207 FU Edmond J. Safra Center for Ethics at Harvard University; NCAA Sports Science Institute; Athena Diagnostics FX Christine M. Baugh received funding from the Edmond J. Safra Center for Ethics at Harvard University to conduct the larger study from which data for this manuscript was derived. Emily Kroshus receives funding from the NCAA Sports Science Institute as a postdoctoral research fellow. Robert A. Stern is a paid consultant to Athena Diagnostics and receives royalties from Psychological Assessment Resources, Inc. He also provides expert consultation to legal teams involved with NCAA and NFL-related litigation. NR 72 TC 15 Z9 15 U1 4 U2 22 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD MAR 1 PY 2015 VL 32 IS 5 BP 314 EP 326 DI 10.1089/neu.2014.3582 PG 13 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CC0SD UT WOS:000350045700004 PM 25155288 ER PT J AU Jacobsen, J Billings, A AF Jacobsen, Juliet Billings, Andrew TI Easing the Burden of Surrogate Decision Making: The Role of a Do-Not-Escalate-Treatment Order SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material ID LIFE-SUSTAINING TREATMENT; INTENSIVE-CARE; ROUTINE STRATEGY; END; SUPPORT; FAMILY; ICU; EXPERIENCE; OTHERS AB We present a case illustrating the common problem of a surrogate decision maker who is psychologically distressed over the medical team's recommendation to withdraw life-sustaining treatment. We suggest how a do-not-escalate-treatment (DNET) order can be helpful in such situations when the usual approaches to withholding or withdrawing care are not acceptable to the surrogate. We define a DNET order, explain when it might be useful, and discuss how it can facilitate a humane, negotiated resolution of differences. C1 [Jacobsen, Juliet] Massachusetts Gen Hosp, Palliat Care Div, Boston, MA 02114 USA. [Billings, Andrew] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Jacobsen, J (reprint author), Massachusetts Gen Hosp, Palliat Care Div, 5 Fruit St,Founders 600, Boston, MA 02114 USA. EM jjacobsen@partners.org NR 29 TC 0 Z9 0 U1 4 U2 6 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 MAR 1 PY 2015 VL 18 IS 3 BP 306 EP 309 DI 10.1089/jpm.2014.0295 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CC1MO UT WOS:000350105200022 PM 25671289 ER PT J AU Chu, CJ Tanaka, N Diaz, J Edlow, BL Wu, O Hamalainen, M Stufflebeam, S Cash, SS Kramer, MA AF Chu, C. J. Tanaka, N. Diaz, J. Edlow, B. L. Wu, O. Haemaelaeinen, M. Stufflebeam, S. Cash, S. S. Kramer, M. A. TI EEG functional connectivity is partially predicted by underlying white matter connectivity SO NEUROIMAGE LA English DT Article DE Probabilistic tractography; Electrical source imaging; Structural networks; DTI; High density EEG ID DEFAULT MODE NETWORK; GRAPH-THEORETICAL ANALYSIS; HUMAN CONNECTOME PROJECT; TEMPORAL-LOBE EPILEPSY; STRUCTURAL CONNECTIVITY; CORTICAL NETWORKS; BRAIN NETWORKS; VISUAL-CORTEX; ANATOMICAL CONNECTIVITY; CEREBRAL-CORTEX AB Over the past decade, networks have become a leading model to illustrate both the anatomical relationships (structural networks) and the coupling of dynamic physiology (functional networks) linking separate brain regions. The relationship between these two levels of description remains incompletely understood and an area of intense research interest. In particular, it is unclear how cortical currents relate to underlying brain structural architecture. In addition, although theory suggests that brain communication is highly frequency dependent, how structural connections influence overlying functional connectivity in different frequency bands has not been previously explored. Here we relate functional networks inferred from statistical associations between source imaging of EEG activity and underlying cortico-cortical structural brain connectivity determined by probabilistic white matter tractography. We evaluate spontaneous fluctuating cortical brain activity over a long time scale (minutes) and relate inferred functional networks to underlying structural connectivity for broadband signals, as well as in seven distinct frequency bands. We find that cortical networks derived from source EEG estimates partially reflect both direct and indirect underlying white matter connectivity in all frequency bands evaluated. In addition, we find that when structural support is absent, functional connectivity is significantly reduced for high frequency bands compared to low frequency bands. The association between cortical currents and underlyingwhite matter connectivity highlights the obligatory interdependence of functional and structural networks in the human brain. The increased dependence on structural support for the coupling of higher frequency brain rhythms provides new evidence for how underlying anatomy directly shapes emergent brain dynamics at fast time scales. (C) 2014 Elsevier Inc. All rights reserved. C1 [Chu, C. J.; Diaz, J.; Edlow, B. L.; Cash, S. S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Chu, C. J.; Tanaka, N.; Edlow, B. L.; Wu, O.; Haemaelaeinen, M.; Stufflebeam, S.; Cash, S. S.] Harvard Univ, Sch Med, Boston, MA USA. [Tanaka, N.; Diaz, J.; Edlow, B. L.; Wu, O.; Haemaelaeinen, M.] MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Tanaka, N.; Wu, O.; Haemaelaeinen, M.; Stufflebeam, S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kramer, M. A.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Chu, CJ (reprint author), 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM cjchu@mgh.harvard.edu FU Burroughs Wellcome Fund; [NIH5K12NS066225] FX CJC is supported by NIH5K12NS066225. MAK is supported by a career award at the scientific interface from the Burroughs Wellcome Fund. NR 93 TC 9 Z9 9 U1 3 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2015 VL 108 BP 23 EP 33 DI 10.1016/j.neuroimage.2014.12.033 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CB4SO UT WOS:000349618600003 PM 25534110 ER PT J AU Sabuncu, MR Bernal-Rusiel, JL Reuter, M Greve, DN Fischl, B AF Sabuncu, Mert R. Bernal-Rusiel, Jorge L. Reuter, Martin Greve, Douglas N. Fischl, Bruce CA Alzheimers Dis Neuroimaging Initia TI Event time analysis of longitudinal neuroimage data (vol 97, pg 9, 2014) SO NEUROIMAGE LA English DT Correction C1 [Sabuncu, Mert R.; Bernal-Rusiel, Jorge L.; Reuter, Martin; Greve, Douglas N.; Fischl, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sabuncu, Mert R.; Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Reuter, Martin] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Sabuncu, MR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM msabuncu@nmr.mgh.harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2015 VL 108 BP 74 EP 74 DI 10.1016/j.neuroimage.2014.12.051 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CB4SO UT WOS:000349618600007 ER PT J AU Bernal-Rusiel, JL Greve, DN Reuter, M Fischl, B Sabuncu, MR AF Bernal-Rusiel, Jorge L. Greve, Douglas N. Reuter, Martin Fischl, Bruce Sabuncu, Mert R. CA Alzheimer's Dis Neuroimaging Initi TI Statistical analysis of longitudinal neuroimage data with Linear Mixed Effects models (vol 66, pg 249, 2013) SO NEUROIMAGE LA English DT Correction C1 [Bernal-Rusiel, Jorge L.; Greve, Douglas N.; Reuter, Martin; Fischl, Bruce; Sabuncu, Mert R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Bernal-Rusiel, Jorge L.; Greve, Douglas N.; Reuter, Martin; Fischl, Bruce; Sabuncu, Mert R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Reuter, Martin] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Fischl, Bruce; Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Sabuncu, MR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM msabuncu@nmr.mgh.harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2015 VL 108 BP 110 EP 110 DI 10.1016/j.neuroimage.2014.12.053 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CB4SO UT WOS:000349618600011 ER PT J AU Bernal-Rusiel, JL Reuter, M Greve, DN Fischl, B Sabuncu, MR AF Bernal-Rusiel, Jorge L. Reuter, Martin Greve, Douglas N. Fischl, Bruce Sabuncu, Mert R. CA Alzheimer's Dis Neuroimaging Initi TI Spatiotemporal linear mixed effects modeling for the mass-univariate analysis of longitudinal neuroimage data (vol 81, pg 358, 2013) SO NEUROIMAGE LA English DT Correction C1 [Bernal-Rusiel, Jorge L.; Reuter, Martin; Greve, Douglas N.; Fischl, Bruce; Sabuncu, Mert R.] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Reuter, Martin] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Fischl, Bruce; Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Sabuncu, MR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM msabuncu@nmr.mgh.harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2015 VL 108 BP 123 EP 123 DI 10.1016/j.neuroimage.2014.12.052 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CB4SO UT WOS:000349618600013 ER PT J AU Cacciatore, S Saccenti, E Piccioli, M AF Cacciatore, Stefano Saccenti, Edoardo Piccioli, Mario TI Hypothesis: The Sound of the Individual Metabolic Phenotype? Acoustic Detection of NMR Experiments SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID BREAST-CANCER; PERSONALIZED MEDICINE; DISEASE; PROFILES; MODELS; HEALTH; TIME; CLASSIFICATION; IDENTIFICATION; METABONOMICS AB We present here an innovative hypothesis and report preliminary evidence that the sound of NMR signals could provide an alternative to the current representation of the individual metabolic fingerprint and supply equally significant information. The NMR spectra of the urine samples provided by four healthy donors were converted into audio signals that were analyzed in two audio experiments by listeners with both musical and non-musical training. The listeners were first asked to cluster the audio signals of two donors on the basis of perceived similarity and then to classify unknown samples after having listened to a set of reference signals. In the clustering experiment, the probability of obtaining the same results by pure chance was 7.04% and 0.05% for non-musicians and musicians, respectively. In the classification experiment, musicians scored 84% accuracy which compared favorably with the 100% accuracy attained by sophisticated pattern recognition methods. The results were further validated and confirmed by analyzing the NMR metabolic profiles belonging to two other different donors. These findings support our hypothesis that the uniqueness of the metabolic phenotype is preserved even when reproduced as audio signal and warrants further consideration and testing in larger study samples. C1 [Cacciatore, Stefano] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Saccenti, Edoardo] Wageningen Univ, Lab Syst & Synthet Biol, NL-6700 AP Wageningen, Netherlands. [Piccioli, Mario] Univ Florence, Magnet Resonance Ctr CERM, I-50019 Florence, Italy. [Piccioli, Mario] Univ Florence, Dept Chem, I-50019 Florence, Italy. RP Piccioli, M (reprint author), Univ Florence, Magnet Resonance Ctr CERM, Via Luigi Sacconi 2, I-50019 Florence, Italy. EM piccioli@cerm.unifi.it RI Piccioli, Mario/M-1994-2015; OI Piccioli, Mario/0000-0001-9882-9754; Cacciatore, Stefano/0000-0001-7052-7156 FU Fondazione Italiana per la Ricerca sul Cancro; Associazione Italiana per la Ricerca sul Cancro FX Leonardo Tenori is gratefully acknowledged for his comments and support. We are grateful to Claudio Luchinat and FiorGen Foundation (Sesto Fiorentino, Italy) for the permission to use part of the MetRef NMR dataset. Stefano Cacciatore was supported by a fellowship from the "Fondazione Italiana per la Ricerca sul Cancro." NR 78 TC 0 Z9 0 U1 0 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 EI 1557-8100 J9 OMICS JI OMICS PD MAR 1 PY 2015 VL 19 IS 3 BP 147 EP 156 DI 10.1089/omi.2014.0131 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CC6EU UT WOS:000350458600002 PM 25748436 ER PT J AU Lee, IS Wallraven, C Kong, J Chang, DS Lee, H Park, HJ Chae, Y AF Lee, In-Seon Wallraven, Christian Kong, Jian Chang, Dong-Seon Lee, Hyejung Park, Hi-Joon Chae, Younbyoung TI When pain is not only pain: Inserting needles into the body evokes distinct reward-related brain responses in the context of a treatment SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Acupuncture; Context; fMRI; Pain; Reward; Therapeutic tool; Ventral striatum ID ACUPUNCTURE EXPECTANCY SCALE; SINGLE-TRIAL FMRI; NUCLEUS-ACCUMBENS; SOMATOSENSORY CORTEX; PLACEBO ANALGESIA; OPIOID ANALGESIA; PERSISTENT PAIN; ACTIVATION; STIMULI; DISSOCIATION AB The aim of this study was to compare behavioral and functional brain responses to the act of inserting needles into the body in two different contexts, treatment and stimulation, and to determine whether the behavioral and functional brain responses to a subsequent pain stimulus were also context dependent. Twenty-four participants were randomly divided into two groups: an acupuncture treatment (AT) group and an acupuncture stimulation (AS) group. Each participant received three different types of stimuli, consisting of tactile, acupuncture, and pain stimuli, and was given behavioral assessments during fMRI scanning. Although the applied stimuli were physically identical in both groups, the verbal instructions differed: participants in the AS group were primed to consider the acupuncture as a painful stimulus, whereas the participants in the AT group were told that the acupuncture was part of therapeutic treatment. Acupuncture yielded greater brain activation in reward-related brain areas (ventral striatum) of the brain in the AT group when compared to the AS group. Brain activation in response to pain stimuli was significantly attenuated in the bilateral secondary somatosensory cortex and the right dorsolateral prefrontal cortex after prior acupuncture needle stimulation in the AT group but not in the AS group. Inserting needles into the body in the context of treatment activated reward circuitries in the brain and modulated pain responses in the pain matrix. Our findings suggest that pain induced by therapeutic tools in the context of a treatment is modulated differently in the brain, demonstrating the power of context in medical practice. (C) 2014 Elsevier Inc. All rights reserved. C1 [Lee, In-Seon; Lee, Hyejung; Park, Hi-Joon; Chae, Younbyoung] Kyung Hee Univ, Coll Korean Med, Acupuncture & Meridian Sci Res Ctr, Seoul 130701, South Korea. [Lee, In-Seon] Univ Tubingen Hosp, Dept Internal Med Psychosomat Med & Psychotherapy, Tubingen, Germany. [Wallraven, Christian; Chae, Younbyoung] Korea Univ, Dept Brain Cognit Engn, Seoul, South Korea. [Kong, Jian] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Chang, Dong-Seon] Max Planck Inst Biol Cybernet, Dept Human Percept Cognit & Act, D-72076 Tubingen, Germany. RP Chae, Y (reprint author), Kyung Hee Univ, Coll Korean Med, Acupuncture & Meridian Sci Res Ctr, 1 Hoegi Dong, Seoul 130701, South Korea. EM ybchae@khu.ac.kr OI Chang, Dong-Seon/0000-0003-4562-1321 FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2011-0009913] FX This research was 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. 2011-0009913). NR 49 TC 6 Z9 6 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD MAR 1 PY 2015 VL 140 BP 148 EP 155 DI 10.1016/j.physbeh.2014.12.030 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA CB4HI UT WOS:000349588400020 PM 25528104 ER PT J AU Kim, SP Gross, CP Smaldone, MC Han, LC Van Houten, H Lotan, Y Svatek, RS Thompson, RH Karnes, RJ Trinh, QD Kutikov, A Shah, ND AF Kim, S. P. Gross, C. P. Smaldone, M. C. Han, L. C. Van Houten, H. Lotan, Y. Svatek, R. S. Thompson, R. H. Karnes, R. J. Trinh, Q-D Kutikov, A. Shah, N. D. TI Perioperative outcomes and hospital reimbursement by type of radical prostatectomy: results from a privately insured patient population SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article ID ROBOTIC SURGERY; UNITED-STATES; CANCER; TECHNOLOGIES; ADOPTION; COST; RISK; CARE; MEN AB BACKGROUND: With the increasing use of robotic surgery in the United States, the comparative effectiveness and differences in reimbursement of minimally invasive radical prostatectomy (MIRP) and open prostatectomy (ORP) in privately insured patients are unknown. Therefore, we sought to assess the differences in perioperative outcomes and hospital reimbursement in a privately insured patient population who were surgically treated for prostate cancer. METHODS: Using a large private insurance database, we identified 17 610 prostate cancer patients who underwent either MIRP or ORP from 2003 to 2010. The primary outcomes were length of stay (LOS), perioperative complications, 90-day readmissions rates and hospital reimbursement. Multivariable regression analyses were used to evaluate for differences in primary outcomes across surgical approaches. RESULTS: Overall, 8981 (51.0%) and 8629 (49.0%) surgically treated prostate cancer patients underwent MIRP and ORP, respectively. The proportion of patients undergoing MIRP markedly rose from 11.9% in 2003 to 72.5% in 2010 (P < 0.001 for trend). Relative to ORP, MIRP was associated with a shorter median LOS (1.0 day vs 3.0 days; P < 0.001) and lower adjusted odds ratio of perioperative complications (OR: 0.82; P < 0.001). However, the 90-day readmission rates of MIRP and ORP were similar (OR: 0.99; P = 0.76). MIRP provided higher adjusted mean hospital reimbursement compared with ORP (US$ 19 292 vs US$ 17 347; P < 0.001). CONCLUSIONS: Among privately insured patients diagnosed with prostate cancer, robotic surgery rapidly disseminated with over 70% of patients undergoing MIRP by 2009-2010. Although MIRP was associated with shorter LOS and modestly better perioperative outcomes, hospitals received higher reimbursement for MIRP compared with ORP. C1 [Kim, S. P.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Sch Med, Inst Urol, Cleveland, OH 44106 USA. [Kim, S. P.; Gross, C. P.] Yale Univ, COPPER Ctr, New Haven, CT USA. [Kim, S. P.] Case Western Reserve Univ, Ctr Reducing Racial Dispar, Cleveland, OH 44106 USA. [Gross, C. P.] Yale Univ, Dept Internal Med, New Haven, CT USA. [Smaldone, M. C.; Kutikov, A.] Fox Chase Canc Ctr, Dept Surg, Philadelphia, PA 19111 USA. [Han, L. C.; Van Houten, H.; Shah, N. D.] Mayo Clin, Div Hlth Care Policy & Res, Rochester, MN USA. [Lotan, Y.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA. [Svatek, R. S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Thompson, R. H.; Karnes, R. J.] Mayo Clin, Dept Urol, Rochester, MN USA. [Trinh, Q-D] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Urol Surg, Boston, MA 02115 USA. [Shah, N. D.] Mayo Clin, Knowledge & Evaluat Res Unit, Rochester, MN USA. RP Kim, SP (reprint author), Case Western Reserve Univ, Univ Hosp Case Med Ctr, Sch Med, Inst Urol, 11100 Euclid Ave,Mailstop LKS5406, Cleveland, OH 44106 USA. EM Simon.Kim@UHhospitals.org FU career development award from the Conquer Cancer Foundation of the American Society of Clinical Oncology FX SPK was supported by a career development award from the Conquer Cancer Foundation of the American Society of Clinical Oncology. The remaining authors declare no conflict of interest. NR 29 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 EI 1476-5608 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD MAR PY 2015 VL 18 IS 1 BP 13 EP 17 DI 10.1038/pcan.2014.38 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CB4VN UT WOS:000349626500002 PM 25311766 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 The association between race and treatment regret among men with recurrent prostate cancer SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article ID QUALITY-OF-LIFE; AFRICAN-AMERICAN MEN; ANDROGEN DEPRIVATION THERAPY; RADICAL PROSTATECTOMY; RACIAL-DIFFERENCES; DECISIONAL REGRET; SATISFACTION; CARE; KNOWLEDGE; MISTRUST AB BACKGROUND: To examine the impact of race on treatment regret among men with recurrent prostate cancer after surgery or radiation. METHODS: The prospective Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry was used to study a cohort of 484 men with biochemically recurrent prostate cancer after radical prostatectomy, external beam radiation or brachytherapy. Multivariable logistic regression was used to model the association between race and treatment regret and to determine whether there was an interaction between race and sexual problems after treatment with regards to treatment regret. RESULTS: Black men (N = 78) were significantly more likely to have treatment regret when compared with non-black men (N = 406; 21.8% versus 12.6%) on univariable analysis (odds ratio (OR) 1.94; 95% confidence interval 1.05-3.56; P = 0.03). On multivariable analysis, black race trended towards but was no longer significantly associated with an increase in treatment regret (adjusted OR (AOR) 1.84 (0.95-3.58); P = 0.071). There was an interaction between race and sexual problems after treatment (P-interaction = 0.02) such that among those without sexual problems, black men had more treatment regret than non-black men (26.7% versus 8.4%: AOR 4.68 (1.73-12.63); P = 0.002), whereas among those with sexual problems, there was no difference in treatment regret between black and non-black men (18.8% versus 17.3%: AOR 1.04 (0.44-2.46); P = 0.93). CONCLUSIONS: Among men with recurrent prostate cancer after surgery or radiation, black men were nearly twice as likely to experience treatment regret. Treating physicians should ensure that patients are fully apprised of the pros and cons of all treatment options to reduce the risk of subsequent regret. C1 [Mahal, B. A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chen, M-H] Univ Connecticut, Dept Stat, Storrs, CT USA. [Bennett, C. L.] South Carolina Coll Pharm, 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 & Urol, New Orleans, LA 70118 USA. [Stein, K.] Novartis, E Hanover, NJ USA. [D'Amico, A. V.; Nguyen, P. L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu FU David and Cynthia Chapin; Prostate Cancer Foundation; Fitz's Cancer Warriors; Hugh Simons in honor of Frank and Anne Simons 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 and a grant from an anonymous family foundation. NR 35 TC 3 Z9 3 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 EI 1476-5608 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD MAR PY 2015 VL 18 IS 1 BP 38 EP 42 DI 10.1038/pcan.2014.42 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CB4VN UT WOS:000349626500006 PM 25348256 ER PT J AU Arora, S Singh, P Singh, PM Trikha, A AF Arora, Shubhangi Singh, Prashant Singh, Preet Mohinder Trikha, Anjan TI PROCALCITONIN LEVELS IN SURVIVORS AND NONSURVIVORS OF SEPSIS: SYSTEMATIC REVIEW AND META-ANALYSIS SO SHOCK LA English DT Review DE Procalcitonin in sepsis; mortality and procalcitonin in sepsis; procalcitonin in nonsurvivors ID CRITICALLY-ILL PATIENTS; C-REACTIVE PROTEIN; INTENSIVE-CARE-UNIT; SUCCESSFUL SURGICAL-TREATMENT; SEPTIC SHOCK; SERUM PROCALCITONIN; ANTIBIOTIC-THERAPY; PROGNOSTIC VALUE; DIAGNOSTIC MARKER; ORGAN FAILURE AB Procalcitonin (PCT) is an acute-phase reactant that has been used to diagnose and potentially track the treatment of sepsis. Procalcitonin values rise initially as the infection sets in and eventually fall with resolution. Its level has been reported to be significantly higher in potential nonsurvivors of a septic episode than among survivors. However, there is also a significant amount of evidence against this. We thus conducted a meta-analysis to pool data from all the available studies regarding PCT levels in survivors and nonsurvivors of sepsis. An extensive literature search was conducted using the key words procalcitonin, sepsis, and prognosis. The references of the relevant studies were also scanned. The data from the eligible studies were extracted and analyzed for any significant pooled mean difference between survivors and nonsurvivors both on days 1 and 3. The mean difference in the day 1 PCT values between survivors and nonsurvivors was found to be statistically significant (P = 0.02). The mean difference on day 3 was also statistically significant (P = 0.002). However, in a subgroup consisting of studies on patients with severe sepsis and septic shock, day 1 difference was not found to be significant (P = 0.62). We found heterogeneity of 90% in our study population, which decreased to 62% after exclusion of studies conducted in emergency department patients. Procalcitonin levels in early stages of sepsis are significantly lower among survivors as compared with nonsurvivors of sepsis. C1 [Arora, Shubhangi] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Singh, Prashant] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Singh, Preet Mohinder; Trikha, Anjan] All India Inst Med Sci, Dept Anaesthesiol, New Delhi 110029, India. RP Singh, PM (reprint author), All India Inst Med Sci, Dept Anaesthesiol, New Delhi 110029, India. EM preetrajpal@gmail.com NR 100 TC 6 Z9 7 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD MAR PY 2015 VL 43 IS 3 BP 212 EP 221 DI 10.1097/SHK.0000000000000305 PG 10 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA CB1UE UT WOS:000349412700002 PM 25423128 ER PT J AU Scherzer, R Bacchetti, P Messerlian, G Goderre, J Maki, PM Seifer, DB Anastos, K Karim, R Greenblatt, RM AF Scherzer, Rebecca Bacchetti, Peter Messerlian, Geralyn Goderre, Johanna Maki, Pauline M. Seifer, David B. Anastos, Kathryn Karim, Roksana Greenblatt, Ruth M. TI Impact of CD4+Lymphocytes and HIV Infection on Anti-Mullerian Hormone Levels in a Large Cohort of HIV-infected and HIV-uninfected Women SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE Anti-Mullerian hormone; CD4 lymphocytes; HIV; menopause; ovarian follicle ID POLYCYSTIC-OVARY-SYNDROME; REPRODUCTIVE-AGED WOMEN; ANTRAL FOLLICLE COUNT; ANTIMULLERIAN HORMONE; PREMENOPAUSAL WOMEN; INTERAGENCY HIV; MENSTRUAL-CYCLE; AMH LEVEL; MENOPAUSE; RESERVE AB ProblemEffects of HIV infection on ovarian function and aging are unclear. Method of studyAnti-Mullerian Hormone (AMH) levels were analyzed in 2621 HIV-infected and 941 uninfected participants using left-censored longitudinal models. ResultsAge-adjusted AMH levels were 16% lower in women with undetectable viraemia and 26% lower in detectable viraemia, relative to uninfected women. Current CD4 count associated with higher AMH in both HIV-infected and HIV-uninfected women. After controlling for current and nadir CD4, AMH was 15% higher in HIV-infected relative to uninfected women, regardless of HIV viraemia. Gravidity, amenorrhea, and nadir total lymphocyte counts associated with higher AMH; hormonal contraceptive use and past weight loss associated with lower AMH. ConclusionsCD4+ lymphocyte counts were associated with AMH in both HIV-infected and uninfected women. After adjustment for CD4 counts and age, HIV infection was associated with higher AMH. CD4 T cells and cellular activation may influence ovarian granulosa cell function. C1 [Scherzer, Rebecca; Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Med, San Francisco Sch Med, San Francisco, CA 94143 USA. [Scherzer, Rebecca] San Francisco VA Med Ctr, San Francisco, CA USA. [Bacchetti, Peter; Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco Sch Med, San Francisco, CA 94143 USA. [Messerlian, Geralyn] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Goderre, Johanna] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Maki, Pauline M.] Univ Illinois, Dept Psychiat, Coll Med, Chicago, IL 60612 USA. [Maki, Pauline M.] Univ Illinois, Dept Psychol, Coll Med, Chicago, IL 60680 USA. [Seifer, David B.] Maimonides Hosp, Brooklyn, NY 11219 USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Karim, Roksana] Univ So Calif, Los Angeles, CA USA. [Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco Sch Pharm, San Francisco, CA 94143 USA. RP Greenblatt, RM (reprint author), Univ Calif San Francisco, Box 1352, San Francisco, CA 94143 USA. EM ruth.greenblatt@ucsf.edu OI Messerlian, Geralyn/0000-0002-9440-3411 FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131] FX Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. These funding sources had no involvement in the design or execution of this study. NR 50 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD MAR PY 2015 VL 73 IS 3 BP 273 EP 284 DI 10.1111/aji.12332 PG 12 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA CB4SJ UT WOS:000349618000009 PM 25339186 ER PT J AU Vasheghani, F Zhang, Y Li, YH Blati, M Fahmi, H Lussier, B Roughley, P Lagares, D Endisha, H Saffar, B Lajeunesse, D Marshall, WK Rampersaud, YR Mahomed, NN Gandhi, R Pelletier, JP Martel-Pelletier, J Kapoor, M AF Vasheghani, Faezeh Zhang, Yue Li, Ying-Hua Blati, Meryem Fahmi, Hassan Lussier, Bertrand Roughley, Peter Lagares, David Endisha, Helal Saffar, Bahareh Lajeunesse, Daniel Marshall, Wayne K. Rampersaud, Y. Raja Mahomed, Nizar N. Gandhi, Rajiv Pelletier, Jean-Pierre Martel-Pelletier, Johanne Kapoor, Mohit TI PPAR gamma deficiency results in severe, accelerated osteoarthritis associated with aberrant mTOR signalling in the articular cartilage SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; PI3K/AKT/MTOR PATHWAY; SELF-DIGESTION; AUTOPHAGY; DISEASE; MICE; PIOGLITAZONE; DEGRADATION; EXPRESSION; RAPAMYCIN AB Objectives We have previously shown that peroxisome proliferator-activated receptor gamma (PPAR gamma), a transcription factor, is essential for the normal growth and development of cartilage. In the present study, we created inducible cartilage-specific PPAR gamma knockout (KO) mice and subjected these mice to the destabilisation of medial meniscus (DMM) model of osteoarthritis (OA) to elucidate the specific in vivo role of PPAR gamma in OA pathophysiology. We further investigated the downstream PPAR gamma signalling pathway responsible for maintaining cartilage homeostasis. Methods Inducible cartilage-specific PPAR gamma KO mice were generated and subjected to DMM model of OA. We also created inducible cartilage-specific PPAR gamma/mammalian target for rapamycin (mTOR) double KO mice to dissect the PPAR gamma signalling pathway in OA. Results Compared with control mice, PPAR gamma KO mice exhibit accelerated OA phenotype with increased cartilage degradation, chondrocyte apoptosis, and the overproduction of OA inflammatory/catabolic factors associated with the increased expression of mTOR and the suppression of key autophagy markers. In vitro rescue experiments using PPAR gamma expression vector reduced mTOR expression, increased expression of autophagy markers and reduced the expression of OA inflammatory/catabolic factors, thus reversing the phenotype of PPAR gamma KO mice chondrocytes. To dissect the in vivo role of mTOR pathway in PPAR gamma signalling, we created and subjected PPAR gamma-mTOR double KO mice to the OA model to see if the genetic deletion of mTOR in PPAR gamma KO mice (double KO) can rescue the accelerated OA phenotype observed in PPAR gamma KO mice. Indeed, PPAR gamma-mTOR double KO mice exhibit significant protection/reversal from OA phenotype. Significance PPAR gamma maintains articular cartilage homeostasis, in part, by regulating mTOR pathway. C1 [Vasheghani, Faezeh; Blati, Meryem; Fahmi, Hassan; Lajeunesse, Daniel; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Kapoor, Mohit] Univ Montreal Hosp Res Ctr CRCHUM, Osteoarthrit Res Unit, Montreal, PQ, Canada. [Zhang, Yue; Li, Ying-Hua; Endisha, Helal; Saffar, Bahareh; Kapoor, Mohit] Univ Hlth Network, Toronto Western Res Inst, Div Genet & Dev, Toronto, ON M5T 2S8, Canada. [Lussier, Bertrand] Univ Montreal, Fac Vet Med, Dept Clin Sci, St Hyacinthe, PQ J2S 7C6, Canada. [Roughley, Peter] McGill Univ, Shriners Hosp, Genet Unit, Montreal, PQ, Canada. [Lagares, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Cambridge, MA 02138 USA. [Lagares, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Dept Med, Cambridge, MA 02138 USA. [Marshall, Wayne K.; Rampersaud, Y. Raja; Mahomed, Nizar N.; Gandhi, Rajiv; Kapoor, Mohit] Toronto Western Hosp, Div Orthoped, Toronto, ON M5T 2S8, Canada. [Kapoor, Mohit] Univ Toronto, Dept Surg, Toronto, ON, Canada. RP Kapoor, M (reprint author), Univ Hlth Network, Toronto Western Hosp, Toronto Western Res Inst, 60 Leonard Ave, Toronto, ON M5T 2S8, Canada. EM mkapoor@uhnresearch.ca FU MK's Canadian Institutes of Health Research Operating Grant [MOP: 126016, MOP: 106567]; Canadian Arthritis Network (CAN)/The Arthritis Society (TAS) FX This work is supported by MK's Canadian Institutes of Health Research Operating Grant MOP: 126016 and MOP: 106567. FV is a recipient of Graduate PhD award from the Canadian Arthritis Network (CAN)/The Arthritis Society (TAS). NR 35 TC 20 Z9 21 U1 1 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2015 VL 74 IS 3 BP 569 EP 578 DI 10.1136/annrheumdis-2014-205743 PG 10 WC Rheumatology SC Rheumatology GA CB1YB UT WOS:000349422800014 PM 25573665 ER PT J AU Cao, Y Hunter, ZR Liu, X Xu, L Yang, G Chen, J Tsakmaklis, N Kanan, S Castillo, JJ Treon, SP AF Cao, Yang Hunter, Zachary R. Liu, Xia Xu, Lian Yang, Guang Chen, Jie Tsakmaklis, Nickolas Kanan, Sandra Castillo, Jorge J. Treon, Steven P. TI CXCR4 WHIM-like frameshift and nonsense mutations promote ibrutinib resistance but do not supplant MYD88(L265P)-directed survival signalling in Waldenstrom macroglobulinaemia cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Waldenstrom macroglobulinaemia; WHIM; CXCR4; MYD88; ibrutinib ID L265P SOMATIC MUTATION; MYD88 L265P AB CXCR4(WHIM) frameshift and nonsense mutations follow MYD88(L265P) as the most common somatic variants in Waldenstrom Macroglobulinaemia (WM), and impact clinical presentation and ibrutinib response. While the nonsense (CXCR4(S338X)) mutation has been investigated, little is known about CXCR4 frameshift (CXCR4(FS)) mutations. We engineered WM cells to express CXCR4(FS) mutations present in patients, and compared their CXCL12 (SDF-1a) induced signalling and ibrutinib sensitivity to CXCR4(wild-type (WT)) and CXCR4(S338X) cells. Following CXCL12 stimulation, CXCR4(FS) and CXCR4(S338X) WM cells showed impaired CXCR4 receptor internalization, and enhanced AKT1 (also termed AKT) and MAPK1 (also termed ERK) activation versus CXCRWT cells (P<005), though MAPK1 activation was more prolonged in CXCR4(S338X) cells (P<005). CXCR4(FS) and CXCR4(S338X) cells, but not CXCR4(WT) cells, were rescued from ibrutinib-triggered apoptosis by CXCL12 that was reversed by AKT1, MAPK1 or CXCR4 antagonists. Treatment with an inhibitor that blocks MYD88(L265P) signalling triggered similar levels of apoptosis that was not abrogated by CXCL12 treatment in CXCR4(WT) and CXCR4(WHIM) cells. These studies show a functional role for CXCR4(FS) mutations in WM, and provide a framework for the investigation of CXCR4 antagonists with ibrutinib in CXCR4(WHIM)-mutated WM patients. Direct inhibition of MYD88(L265P) signalling overcomes CXCL12 triggered survival effects in CXCR4(WHIM)-mutated cells supporting a primary role for this survival pathway in WM. C1 [Cao, Yang; Hunter, Zachary R.; Liu, Xia; Xu, Lian; Yang, Guang; Chen, Jie; Tsakmaklis, Nickolas; Kanan, Sandra; Castillo, Jorge J.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Cao, Yang; Liu, Xia; Yang, Guang; Castillo, Jorge J.; Treon, Steven P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hunter, Zachary R.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M548,450 Brookline Ave, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu OI Hunter, Zachary/0000-0002-1689-1691 FU Leukemia and Lymphoma Society; Edward and Linda Nelson Fund for WM Research; Kerry Robertson Fund for WM Studies FX The authors acknowledge the generous support of the Leukemia and Lymphoma Society for a Translational Research Grant, Peter S. Bing M.D., the Edward and Linda Nelson Fund for WM Research, the Kerry Robertson Fund for WM Studies for their generous support of this research work. NR 20 TC 18 Z9 18 U1 2 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 MAR PY 2015 VL 168 IS 5 BP 701 EP 707 DI 10.1111/bjh.13200 PG 7 WC Hematology SC Hematology GA CB4PW UT WOS:000349611300011 PM 25371371 ER PT J AU Becker, SJE Teunis, T Blauth, J Kortlever, JTP Dyer, GSM Ring, D AF Becker, Stephanie J. E. Teunis, Teun Blauth, Johann Kortlever, Joost T. P. Dyer, George S. M. Ring, David TI Medical Services and Associated Costs Vary Widely Among Surgeons Treating Patients With Hand Osteoarthritis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID GEOGRAPHIC-VARIATION; REGIONAL-VARIATION; CARE; PREVALENCE AB There are substantial variations in medical services that are difficult to explain based on differences in pathophysiology alone. The scale of variation and the number of people affected suggest substantial potential to lower healthcare costs with the reduction of practice variation. Our study assessed practice variation across three affiliated urban sites in one city in the United States and related healthcare costs following the diagnosis of hand osteoarthritis (OA) in patients. (1) What are the factors associated with increased costs and surgery in the first year after diagnosis of hand OA? (2) How much practice variation exists among hand surgeons in terms of the number of patient visits, use of imaging tests, use of injections, occupational therapy use, and surgery? (3) What proportion of total cost is accounted for by patients who consult with an additional provider? Patients receiving a new diagnosis of primary hand OA between January 1, 2007, and December 31, 2011, were identified from the research database of three affiliated urban hospitals in a single city in the United States. We included 2814 patients (69%, 1929 women) treated by six hand surgeons. We recorded all visits, imaging tests, injections, occupational therapy visits, and surgical procedures in the first year after that diagnosis. Costs were extracted from the Medicare Physician Fee Schedule. Reliability of the database was assessed by manual checking of 120 patient charts (4.3% of all data); reliability was determined to be 94% (113 of 120) for diagnoses, 97% (116 of 120) correct surgeon, 100% (120 of 120) second surgeon, 99% (278 of 282) visits, 99% (132 of 134) imaging procedures, 92% (11 of 12) injections, 95% (21 of 22) surgical procedures, and 85% (102 of 120) prescribing occupational therapy. Predictors of increased costs included younger patient age (regression coefficient [beta] -3.5, semipartial R-2 0.0049, 95% confidence interval [CI] -5.4 to -1.7, p < 0.001), seeing a second surgeon (beta 283, semipartial R-2 0.0095, 95% CI 176-391, p < 0.001), and specific surgeons (surgeon 1: beta -243, semipartial R-2 0.026, 95% CI -298 to -188, p < 0.001; surgeon 2: beta -177, semipartial R-2 0.0090, 95% CI -246 to -109, p < 0.001; surgeon 6: beta 124, semipartial R-2 0.0050, 95% CI 59-189, p < 0.001) (adjusted R-2 = 0.056). Similarly, factors associated with increased surgical intervention included younger patient age (beta -0.0026, semipartial R-2 0.0071, 95% CI -0.0037 to -0.0015, p < 0.001), male sex (beta 0.041, semipartial R-2 0.0028, 95% CI -0.069 to -0.012, p = 0.005), seeing a second surgeon (beta 0.16, semipartial R-2 0.0091, 95% CI 0.094-0.22, p < 0.001), and specific surgeons (surgeon 1: beta -0.14, semipartial R-2 0.026, 95% CI -0.18 to -0.11, p < 0.001; surgeon 2: beta -0.13, semipartial R-2 0.014, 95% CI -0.17 to -0.091, p < 0.001). There were large variations in the average number of visits (1.5-fold), imaging tests (threefold), use of injections (51-fold), occupational therapy (twofold), and surgery rates (sevenfold) among providers. One hundred twenty patients (4.3%) consulted a second surgeon within the first year after receiving the diagnosis of hand OA, which accounted for 8.1% (USD 68,826/USD 845,304) of the total costs. Patients who saw additional providers and who were of younger age incurred higher costs and a greater likelihood of undergoing surgery; the latter was also greater in male patients. Use of medical services and associated costs vary widely among providers treating patients with hand OA. Initiatives addressing practice variation-increased use of decision aids, for example-merit additional study. Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence. C1 [Becker, Stephanie J. E.; Teunis, Teun; Blauth, Johann; Kortlever, Joost T. P.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Dyer, George S. M.] Harvard Univ, Sch Med, Orthopaed Hand & Upper Extrem Serv, Brigham & Womens Hosp,Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA. EM dring@mgh.harvard.edu FU Anna Foundation\NOREF (Oegstgeest, The Netherlands); Genootschap Noorthey (Bussum, The Netherlands); Stichting Fonds Doctor Catharine van Tussenbroek (Amsterdam, The Netherlands); Stichting Vreedefonds (Amsterdam, The Netherlands); Prince Bernhard Culture Fund & Kuitse Fung (Amsterdam, The Netherlands); Fundatie van de Vrijvrouwe van Renswoude te's-Gravenhage (The Hague, The Netherlans); Wright Medical (Memphis, TN, USA); Skeletal Dynamics (Miami, FL, USA); Biomet (Warsaw, IN, USA); AO North America (Paoli, PA, USA); AO International (Dubendorf, Switzerland) FX One of the authors (SJEB) is supported by Dutch research grants from Anna Foundation vertical bar NOREF (less than USD 10,000) (Oegstgeest, The Netherlands), Genootschap Noorthey (less than USD 10,000) (Bussum, The Netherlands), Stichting Fonds Doctor Catharine van Tussenbroek (less than USD 10,000) (Amsterdam, The Netherlands), and Stichting Vreedefonds (less than USD 10,000) (Amsterdam, The Netherlands). One of the authors (TT) received research grants from the Prince Bernhard Culture Fund & Kuitse Fung (less than USD 10,000) (Amsterdam, The Netherlands) and Fundatie van de Vrijvrouwe van Renswoude te's-Gravenhage (less than USD 10,000) (The Hague, The Netherlans). One of the authors (DR) certifies that he, or a member of his immediate family, has or may receive payments or benefits, during the study period from Wright Medical (less than USD 10,000) (Memphis, TN, USA); Skeletal Dynamics (less than USD 10,000) (Miami, FL, USA); Biomet (less than USD 10,000) (Warsaw, IN, USA); AO North America (less than USD 10,000) (Paoli, PA, USA); and AO International (less than USD 10,000) (Dubendorf, Switzerland). NR 24 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2015 VL 473 IS 3 BP 1111 EP 1117 DI 10.1007/s11999-014-3912-3 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CA9KM UT WOS:000349242200051 PM 25171936 ER PT J AU Menendez, ME van Dijk, CN Ring, D AF Menendez, Mariano E. van Dijk, C. Niek Ring, David TI Who Leaves the Hospital Against Medical Advice in the Orthopaedic Setting? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID DISCHARGE; OUTCOMES; RISK; ARTHROPLASTY; SURGERY; CARE; READMISSION; PREDICTORS; MORTALITY; DISEASE AB Patients who leave the hospital against medical advice are at risk for readmission and for a variety of complications and are likely to consume more healthcare resources. However, little is known about which factors, if any, may be associated with self-discharge (discharge against medical advice) among orthopaedic inpatients. We studied the frequency and factors associated with self-discharge in patients hospitalized for orthopaedic trauma and musculoskeletal infection. Using discharge records from the Nationwide Inpatient Sample (2002-2011), we identified approximately 7,067,432 patient hospitalizations for orthopaedic trauma and 5,488,686 for musculoskeletal infection. We calculated the proportions of admissions that ended in self-discharge for both trauma and infection patients; then, we examined patient demographics, diagnoses, and hospital factors. Multivariable logistic regression models were constructed to determine independent predictors of self-discharge. Approximately one in 333 (0.3%) patients hospitalized for an isolated fracture and one in 47 (2.1%) patients with musculoskeletal infection left against medical advice. Patient characteristics associated with self-discharge included age < 75 years (trauma: odds ratio [OR] 2.7, 95% confidence interval [CI] 2.5-2.8, p < 0.001; infection: OR 3.9, 95% CI 3.8-4.1, p < 0.001), male sex (trauma: OR 1.7, 95% CI 1.7-1.8, p < 0.001; infection: OR 1.4, 95% CI 1.3-1.4, p < 0.001), black race/ethnicity (trauma: OR 1.5, 95% CI 1.4-1.6, p < 0.001; infection: OR 1.1, 95% CI 1.1-1.1, p < 0.001), low household income (trauma: OR 1.5, 95% CI 1.4-1.5, p < 0.001; infection: OR 1.4, 95% CI 1.4-1.4, p < 0.001), nonprivate insurance (Medicare [trauma: OR 1.7, 95% CI 1.6-1.8, p < 0.001; infection: OR 2.5, 95% CI 2.4-2.5, p < 0.001] and Medicaid [trauma: OR 2.6, 95% CI 2.5-2.7, p < 0.001; infection: OR 3.2, 95% CI 3.2-3.3, p < 0.001]), and no insurance coverage (trauma: OR 3.0, 95% CI 2.9-3.1, p < 0.001; infection: OR 3.5, 95% CI 3.4-3.5, p < 0.001), less medical comorbidity (trauma: OR 0.94 per one-unit increase in the number of comorbidities, 95% CI 0.93-0.95, p < 0.001; infection: OR 0.88, 95% CI 0.87-0.88, p < 0.001), alcohol (trauma: OR, 2.3, 95% 2.2-2.4, p < 0.001; infection: OR 1.5, 95% CI 1.5-1.5, p < 0.001), opioid (trauma: OR 2.9, 95% CI 2.7-3.1, p < 0.001; infection: OR 4.4, 95% CI 4.3-4.4, p < 0.001) and nonopioid drug abuse (trauma: OR, 2.0, 95% CI 1.9-2.1, p < 0.001; infection: OR 2.8, 95% CI 2.8-2.9, p < 0.001), psychosis (trauma: OR 1.3, 95%CI 1.2-1.3, p < 0.001; infection: OR 1.3, 95% CI 1.3, 1.4, p < 0.001), and AIDS/HIV infection (trauma: OR 1.5, 95% CI 1.2-1.8, p < 0.001; infection: OR 1.3, 95% CI 1.3-1.4, p < 0.001). Patients with upper extremity fractures (OR 1.9, 95% CI 1.8-1.9, p < 0.001) or fractures of the neck and trunk (OR 2.1, 95% CI 2.0-2.2, p < 0.001) were more likely to leave against medical advice than patients with lower extremity fractures. Among infection hospitalizations, patients with cellulitis had the highest odds of self-discharge compared with carbuncle/furuncle (OR 1.3, 95% CI 1.2-1.5, p < 0.001). Self-discharges were more likely to occur at hospitals of larger size (trauma: OR 1.2, 95% CI 1.1-1.2, p < 0.001; infection: nonsignificant), located in urban settings (trauma: OR 1.3, 95% CI 1.2-1.4, p < 0.001; infection: OR 1.6, 95% CI 1.5-1.6, p < 0.001), and in the Northeast (trauma: OR 1.7, 95% CI 1.6-1.8, p < 0.001; infection: OR 1.6, 95% CI 1.6-1.6, p < 0.001) than at small, rural hospitals in the South. Our data can be used to promptly identify orthopaedic inpatients at higher risk of self-discharge on admission and target interventions to optimize treatment adherence. Strategies to enhance physician communication skills among patients with low health literacy, improve cultural sensitivity, and proactively address substance abuse issues early during hospital admission may aid in preventing discharge dilemmas and merit additional study. Level III, prognostic study. See the Instructions for Authors for complete description of levels of evidence. C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. [van Dijk, C. Niek] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM marianofurrer@gmail.com NR 44 TC 5 Z9 5 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2015 VL 473 IS 3 BP 1140 EP 1149 DI 10.1007/s11999-014-3924-z PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CA9KM UT WOS:000349242200055 PM 25187333 ER PT J AU Shikari, H Amparo, F Saboo, U Dana, R AF Shikari, Hasanain Amparo, Francisco Saboo, Ujwala Dana, Reza TI Onset of Ocular Graft-Versus-Host Disease Symptoms After Allogeneic Hematopoietic Stem Cell Transplantation SO CORNEA LA English DT Article DE ocular graft-versus-host disease; dry eye; allogeneic hematopoietic stem cell transplant ID BONE-MARROW-TRANSPLANTATION; UNRELATED DONOR TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; RISK-FACTORS; DRY EYE; METHOTREXATE; PROPHYLAXIS; COMPLICATIONS; CYCLOSPORINE; PREVALENCE AB Objective: To study the factors affecting the time to onset of ocular graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: A retrospective chart review of 200 patients with ocular GVHD was performed to evaluate the association between various donor-recipient characteristics and the time to onset of ocular GVHD after allo-HSCT. Results: The median time to onset of chronic ocular GVHD after allo-HSCT was 293 days (range, 26-2308 days). Patients receiving fully human leukocyte antigen (HLA)-matched transplants had a delayed onset of ocular GVHD (median, 294 days) compared with mismatched transplants (219 days; P = 0.029). HLA-matched transplants from related donors had delayed onset of ocular GVHD (307 days) compared with HLA-matched (286 days; P = 0.168) and HLA-mismatched (231 days; P = 0.015) transplants from unrelated donors. Ocular GVHD followed systemic GVHD in 76% of patients but preceded systemic disease in 7%, occurred concurrently in 15%, and was not associated with systemic GVHD in 2% of patients. The time elapsed between the occurrence of systemic and ocular GVHD was significantly longer in matched-related transplants (250 days) than in matched-unrelated transplants (120 days; P = 0.004). Conclusions: The onset of ocular GVHD after allo-HSCT is variable and is influenced by donor-recipient matching characteristics. In the majority of patients with GVHD, ocular involvement follows the occurrence of systemic manifestations; however, importantly, it can also precede or develop independently of systemic disease in a minority of patients. Regular ophthalmic follow-up is recommended after allo-HSCT regardless of concurrent systemic GVHD status. C1 [Shikari, Hasanain; Amparo, Francisco; Saboo, Ujwala; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU National Institutes of Health [EY19098] FX Supported by the National Institutes of Health (grant EY19098). NR 35 TC 7 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD MAR PY 2015 VL 34 IS 3 BP 243 EP 247 PG 5 WC Ophthalmology SC Ophthalmology GA CB2JS UT WOS:000349453900004 PM 25603230 ER PT J AU Chang, HYP Luo, ZK Chodosh, J Dohlman, CH Colby, KA AF Chang, Han-Ying Peggy Luo, Zhonghui Katie Chodosh, James Dohlman, Claes H. Colby, Kathryn A. TI Primary Implantation of Type I Boston Keratoprosthesis in Nonautoimmune Corneal Diseases SO CORNEA LA English DT Article DE Primary; Boston; KPro ID PENETRATING KERATOPLASTY; RISK-FACTORS; GRAFT FAILURE; MICROBIAL KERATITIS; HERPETIC-KERATITIS; TRANSPLANTATION; ANIRIDIA; OUTCOMES; PROGNOSIS; COMPLICATIONS AB Purpose: The aim of this study was to report outcomes of type I Boston keratoprosthesis (KPro) as primary corneal surgery in nonautoimmune corneal disorders. Methods: In this retrospective, observational, large single-center case series of 43 eyes (37 patients) that were followed for an average of 39 months (1-6 years), primary implantation of the type I Boston KPro was performed in all patients. Visual acuity at year 1, visual acuity at last follow-up, and postoperative complication rates were examined for all eyes. Results: Preoperative best-corrected visual acuity ranged from 20/60 to light perception, with vision of 20/200 or worse in 88%. Vision was >= 20/200 at 1 year in 77% of eyes (P < 0.0001). Complications included retroprosthetic membrane formation (51%), glaucoma progression (47%), corneal melt (19%), and sterile vitritis (14%). Conclusions: In a large series with long follow-up, primary Boston KPro effectively restored vision. Close follow-up is needed to manage the known complications after Boston KPro. C1 [Chang, Han-Ying Peggy; Luo, Zhonghui Katie; Chodosh, James; Dohlman, Claes H.; Colby, Kathryn A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Chang, HYP (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM hpchang@meei.harvard.edu NR 45 TC 5 Z9 5 U1 5 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD MAR PY 2015 VL 34 IS 3 BP 264 EP 270 PG 7 WC Ophthalmology SC Ophthalmology GA CB2JS UT WOS:000349453900008 PM 25611395 ER PT J AU Liu, Y Kam, WR Ding, J Sullivan, DA AF Liu, Yang Kam, Wendy R. Ding, Juan Sullivan, David A. TI Can Tetracycline Antibiotics Duplicate the Ability of Azithromycin to Stimulate Human Meibomian Gland Epithelial Cell Differentiation? SO CORNEA LA English DT Article DE meibomian gland; azithromycin; doxycycline; minocycline; tetracycline ID INDUCED PHOSPHOLIPIDOSIS; INTERNATIONAL WORKSHOP; DYSFUNCTION; SUBCOMMITTEE; LIVER AB Purpose: Azithromycin and tetracyclines are commonly prescribed in the United States for the treatment of meibomian gland dysfunction (MGD). The efficacy of these antibiotics has been believed to be their antiinflammatory and antibacterial actions, which suppress MGD-associated posterior blepharitis and growth of lid bacteria. However, we recently discovered that azithromycin can act directly on human meibomian gland epithelial cells (HMGECs) to stimulate their function. In this study, we sought to determine whether tetracycline antibiotics can duplicate this azithromycin effect. Methods: Immortalized HMGEC were cultured in the presence of a vehicle, azithromycin, doxycycline, minocycline, or tetracycline for 5 days. Cells were evaluated for cholesterol and neutral lipid staining, and the lipid composition of cellular lysates was analyzed by high-performance thin-layer chromatography. Results: Our results demonstrate that azithromycin's ability to stimulate the differentiation of human meibomian gland cells is unique, and is not duplicated by doxycycline, minocycline, or tetracycline. Azithromycin, but not the other antibiotics, significantly increased the cellular accumulation of cholesterol, cholesterol esters, phospholipids, and lysosomes. These differentiative actions of azithromycin were paralleled by an increased expression of sterol regulatory element-binding protein 1. Conclusions: Our findings show that the stimulatory effects of azithromycin on HMGEC function are unique and are not duplicated by the antibiotics doxycycline, minocycline, or tetracycline. Our results further suggest that this stimulatory influence of azithromycin may contribute to its beneficial effect in treating MGD and its associated evaporative dry eye disease. C1 Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Liu, Y (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM yang_liu@meei.harvard.edu FU NIH [EY05612]; Margaret S. Sinon Scholar in Ocular Surface Research Fund; Guoxing Yao Research Fund FX Supported by NIH grant EY05612, the Margaret S. Sinon Scholar in Ocular Surface Research Fund, and the Guoxing Yao Research Fund. NR 22 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD MAR PY 2015 VL 34 IS 3 BP 342 EP 346 PG 5 WC Ophthalmology SC Ophthalmology GA CB2JS UT WOS:000349453900022 PM 25611398 ER PT J AU Jia, HB Hu, SN Uemura, S Park, SJ Jang, Y Prasad, A Lee, S Soeda, T Abtahian, F Vergallo, R Tian, JW Lee, H Stone, PH Yu, B Jang, IK AF Jia, Haibo Hu, Sining Uemura, Shiro Park, Seung-Jung Jang, Yangsoo Prasad, Abhiram Lee, Stephen Soeda, Tsunenari Abtahian, Farhad Vergallo, Rocco Tian, Jinwei Lee, Hang Stone, Peter H. Yu, Bo Jang, Ik-Kyung TI Insights into the spatial distribution of lipid-rich plaques in relation to coronary artery bifurcations: an in-vivo optical coherence tomography study SO CORONARY ARTERY DISEASE LA English DT Article DE bifurcation; distribution; optical coherence tomography; vulnerable plaque ID INTRAVASCULAR ULTRASOUND ANALYSIS; SHEAR-STRESS; ATHEROSCLEROTIC PLAQUES; VIRTUAL HISTOLOGY; RUPTURE; LESIONS; VULNERABILITY; CLASSIFICATION; LOCALIZATION; MORPHOLOGY AB Objectives The aim of this study was to investigate the spatial location of vulnerable plaques at coronary artery bifurcations using frequency domain-optical coherence tomography. Background In-vivo data on geometric location of vulnerable plaques in relation to coronary bifurcation are limited. Materials and methods A total of 40 patients with left anterior descending artery bifurcation were studied. Plaque characteristics in five regions in relation to a side branch were compared: opposite flow divider (OFD); bifurcation site (BF); main branch side proximal (MBP); side branch side proximal (SBP); and flow divider (FD). Frequency domain-optical coherence tomography was used for plaque characterization. Results Seventy-two lipid-rich plaques and 15 thin-cap fibroatheroma (TCFA) were detected in 220 regions of 44 bifurcations. Overall, the main branch side had more vulnerable characteristics compared with the side branch side. The FD was rarely affected by lipid accumulation. The OFD showed the highest prevalence of lipid-rich plaques [47.7% (OFD) vs. 45.5% (MBP), 43.2% (BF), 18.2% (SBP), and 9.1% (FD), P < 0.0001] and TCFA [20.5% (OFD) vs. 6.8% (MBP), 6.8% (BF), 2.2% (SBP), and 0.0% (FD), P < 0.001] and the thinnest fibrous cap [88.7 +/- 43.7 mu m (OFD) vs. 123.5 +/- 62.7 mu m (MBP), 149.6 +/- 77.0 mu m (BF), 157.4 +/- 65.4 mu m (SBP), and 163.6 +/- 76.9 mu m (FD), P = 0.002] compared with other regions. Conclusion Lipid accumulation tends to develop in the zone opposite the side branch. TCFA was localized predominantly in the region OFD, whereas FD was rarely affected. Coron Artery Dis 26: 133-141 Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Jia, Haibo; Hu, Sining; Tian, Jinwei; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin 150086, Peoples R China. [Jia, Haibo; Hu, Sining; Tian, Jinwei; Yu, Bo] Chinese Minist Educ, Key Lab Myocardial Ischemia, Harbin, Peoples R China. [Lee, Stephen] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Jia, Haibo; Hu, Sining; Soeda, Tsunenari; Abtahian, Farhad; Vergallo, Rocco; Tian, Jinwei; Jang, Ik-Kyung] Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Stone, Peter H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div, Boston, MA 02115 USA. [Uemura, Shiro] Nara Med Univ, Dept Med 1, Nara, Japan. [Park, Seung-Jung] Asan Med Ctr, Div Cardiol, Seoul, South Korea. [Jang, Yangsoo] Yonsei Univ, Coll Med, Severance Cardiovasc Hosp, Div Cardiol, Seoul, South Korea. [Prasad, Abhiram] Univ London, London, England. RP Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Key Lab Myocardial Ischemia,Chinese Minist Educ, 246 Xuefu Rd, Harbin 150086, Peoples R China. EM yubodr@163.com FU LightLab Imaging/St Jude Medical; National Natural Science Foundation of China [81200076, 81300201, 81330033, 30871064]; Open Foundation of Key Laboratory of Myocardial Ischemia (Harbin Medical University); Chinese Ministry of Education [KF201205]; Enrico ed Enrica Sovena Foundation, Italy FX This study was supported by grants from LightLab Imaging/St Jude Medical (I.-K.J.), National Natural Science Foundation of China (81200076/H.J., 81300201/J.T., 81330033/B.Y., 30871064/B.Y.), Open Foundation of Key Laboratory of Myocardial Ischemia (Harbin Medical University), Chinese Ministry of Education (KF201205/H.J.), Enrico ed Enrica Sovena Foundation, Italy (R.V.). NR 33 TC 4 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0954-6928 EI 1473-5830 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD MAR PY 2015 VL 26 IS 2 BP 133 EP 141 DI 10.1097/MCA.0000000000000188 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CB2JD UT WOS:000349452300009 PM 25356817 ER PT J AU Dewundara, S Pasquale, LR AF Dewundara, Samantha Pasquale, Louis R. TI Exfoliation syndrome: a disease with an environmental component SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Review DE coffee consumption; dietary folate; environmental factors; exfoliation syndrome; latitude effect; solar exposure ID RETINAL VEIN OCCLUSION; OPEN-ANGLE GLAUCOMA; 1 GENE POLYMORPHISMS; PSEUDOEXFOLIATION SYNDROME; PLASMA HOMOCYSTEINE; LOXL1 GENE; ULTRAVIOLET-RADIATION; COFFEE CONSUMPTION; OXIDATIVE STRESS; AQUEOUS-HUMOR AB Purpose of review Exfoliation syndrome (XFS), the most common cause of secondary open angle glaucoma, is associated with significant ocular morbidity. Recent studies have pointed toward environmental components that may alter the risk of XFS development. This review focuses on the recent studies elucidating the role of environmental factors that play a role in the development of exfoliation syndrome. Recent findings In XFS, aberrant microfibril formation emanating from the cell-extracellular matrix interface admixes with other macromolecules and is cross-linked by lysyl oxidase like 1 (LOXL1) activity. A common gene variant in the LOXL1 enzyme, an enzyme critical for enhancing the tensile strength of collagen and elastin in extracellular matrices, has been found in approximately 90% of XFS cases. However, approximately 80% of controls also have disease-associated LOXL1 gene variants. These findings point toward other nongenetic factors influencing the development of XFS. Increasing latitude, solar radiation, climatic variables and dietary factors such as high coffee consumption and low dietary folate intake are among the nongenetic factors associated with increased risk of XFS. Summary A greater understanding of the environmental components associated with XFS may lead to lifestyle preventive strategies to ameliorate disease burden. C1 [Dewundara, Samantha; Pasquale, Louis R.] Dept Ophthalmol, Boston, MA USA. [Pasquale, Louis R.] Harvard Univ, Sch Med, Massachusetts Eye & Ear, Boston, MA USA. [Pasquale, Louis R.] Brigham & Womens Hosp, Div Network Med, Boston, MA 02115 USA. RP Pasquale, LR (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu FU Arthur Ashley Foundation; National Institutes of Health [EY020928]; Harvard Medical School Distinguished Ophthalmology Scholar Award FX The Arthur Ashley Foundation, grant # EY020928 from the National Institutes of Health, and a Harvard Medical School Distinguished Ophthalmology Scholar Award supported this work. NR 65 TC 5 Z9 5 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8738 EI 1531-7021 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD MAR PY 2015 VL 26 IS 2 BP 78 EP 81 DI 10.1097/ICU.0000000000000135 PG 4 WC Ophthalmology SC Ophthalmology GA CB0XZ UT WOS:000349352300002 PM 25594763 ER PT J AU Germain, M Pezzolesi, MG Sandholm, N McKnight, AJ Susztak, K Lajer, M Forsblom, C Marre, M Parving, HH Rossing, P Toppila, I Skupien, J Roussel, R Ko, YA Ledo, N Folkersen, L Civelek, M Maxwell, AP Tregouet, DA Groop, PH Tarnow, L Hadjadj, S AF Germain, Marine Pezzolesi, Marcus G. Sandholm, Niina McKnight, Amy J. Susztak, Katalin Lajer, Maria Forsblom, Carol Marre, Michel Parving, Hans-Henrik Rossing, Peter Toppila, Iiro Skupien, Jan Roussel, Ronan Ko, Yi-An Ledo, Nora Folkersen, Lasse Civelek, Mete Maxwell, Alexander P. Tregouet, David-Alexandre Groop, Per-Henrik Tarnow, Lise Hadjadj, Samy TI SORBS1 gene, a new candidate for diabetic nephropathy: results from a multi-stage genome-wide association study in patients with type 1 diabetes SO DIABETOLOGIA LA English DT Article DE Diabetic nephropathy; GWAS; Kidney; Sorbin; Type 1 diabetes ID SUSCEPTIBILITY GENES; KIDNEY-DISEASE; EXPRESSION AB The genetic determinants of diabetic nephropathy remain poorly understood. We aimed to identify novel susceptibility genes for diabetic nephropathy. We performed a genome-wide association study using 1000 Genomes-based imputation to compare type 1 diabetic nephropathy cases with proteinuria and with or without renal failure with control patients who have had diabetes for more than 15 years and no evidence of renal disease. None of the single nucleotide polymorphisms (SNPs) tested in a discovery cohort composed of 683 cases and 779 controls reached genome-wide statistical significance. The 46 top hits (p < 10(-5)) were then sought for first-stage analysis in the Genetics of Kidneys in Diabetes US (US-GoKinD) study, an independent population of 820 cases and 885 controls. Two SNPs in strong linkage disequilibrium with each other and located in the SORBS1 gene were consistently and significantly (p < 10(-4)) associated with diabetic nephropathy. The minor rs1326934-C allele was less frequent in cases than in controls (0.34 vs 0.43) and was associated with a decreased risk for diabetic nephropathy (OR 0.70; 95% CI 0.60, 0.82). However, this association was not observed in a second stage with two additional diabetic nephropathy cohorts, the All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK and Republic of Ireland (UK-ROI; p = 0.15) and the Finnish Diabetic Nephropathy (FinnDiane; p = 0.44) studies, totalling 2,142 cases and 2,494 controls. Altogether, the random-effect meta-analysed rs1326934-C allele OR for diabetic nephropathy was 0.83 (95% CI 0.72, 0.96; p = 0.009). These data suggest that SORBS1 might be a gene involved in diabetic nephropathy. C1 [Germain, Marine; Tregouet, David-Alexandre] Univ Paris 06, Sorbonne Univ, UMR S 1166, Team Genom & Pathophysiol Cardiovasc Dis, Paris, France. [Germain, Marine; Tregouet, David-Alexandre] INSERM, UMR S 1166, Team Genom & Pathophysiol Cardiovasc Dis, Paris, France. [Germain, Marine; Tregouet, David-Alexandre] ICAN Inst Cardiometab & Nutr, F-75013 Paris, France. [Pezzolesi, Marcus G.; Skupien, Jan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Pezzolesi, Marcus G.; Skupien, Jan] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sandholm, Niina; Forsblom, Carol; Toppila, Iiro; Groop, Per-Henrik] Biomedicum Helsinki, Folkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland. [Sandholm, Niina; Forsblom, Carol; Toppila, Iiro; Groop, Per-Henrik] Univ Helsinki, Cent Hosp, Dept Med, Div Nephrol, Helsinki, Finland. [Sandholm, Niina] Aalto Univ, Dept Biomed Engn & Computat Sci, Espoo, Finland. [McKnight, Amy J.; Maxwell, Alexander P.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. [Susztak, Katalin; Ko, Yi-An; Ledo, Nora] Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Lajer, Maria; Rossing, Peter; Tarnow, Lise] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Marre, Michel; Roussel, Ronan] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Marre, Michel; Roussel, Ronan] Hop Bichat Claude Bernard, AP HP, F-75877 Paris, France. [Marre, Michel; Roussel, Ronan] Dept Hosp Univ FIRE, Paris, France. [Marre, Michel; Roussel, Ronan] Ctr Rech Cordeliers, INSERM, U1138, Paris, France. [Parving, Hans-Henrik; Rossing, Peter; Tarnow, Lise] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Parving, Hans-Henrik] Univ Copenhagen, Rigshosp, Dept Med Endocrinol, DK-2100 Copenhagen, Denmark. [Rossing, Peter] Univ Copenhagen, Fac Hlth, Ctr Basic Metab Res, Novo Nordisk Fdn, Copenhagen, Denmark. [Skupien, Jan] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. [Folkersen, Lasse] Dept PharmacoGenet, Copenhagen, Denmark. [Folkersen, Lasse] Karolinska Hosp, Atherosclerosis Res Unit, S-10401 Stockholm, Sweden. [Civelek, Mete] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Maxwell, Alexander P.] Belfast City Hosp, Reg Nephrol Unit, Belfast BT9 7AD, Antrim, North Ireland. [Groop, Per-Henrik] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. [Tarnow, Lise] Nordsjaellands Hosp, Hillerod, Denmark. [Hadjadj, Samy] Univ Poitiers, UFR Med Pharm, Ctr Invest Clin, Poitiers, France. [Hadjadj, Samy] CHU Poitiers, Serv Endocrinol Diabetol, F-86021 Poitiers, France. [Hadjadj, Samy] INSERM, CIC1402, Poitiers, France. [Hadjadj, Samy] INSERM, U1082, Poitiers, France. RP Hadjadj, S (reprint author), CHU Poitiers, Serv Endocrinol Diabetol, BP 577, F-86021 Poitiers, France. EM samy.hadjadj@gmail.com RI Ledo, Nora/O-2296-2015; Tregouet, David-Alexandre/E-3961-2016; OI Ledo, Nora/0000-0002-2439-9218; Sandholm, Niina/0000-0003-4322-6942; Marre, Michel/0000-0002-3071-1837; rossing, peter/0000-0002-1531-4294; Maxwell, Alexander P./0000-0002-6110-7253; Civelek, Mete/0000-0002-8141-0284; Folkersen, Lasse/0000-0003-0708-9530 FU NIDDK NIH HHS [R01 DK087635] NR 11 TC 3 Z9 4 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2015 VL 58 IS 3 BP 543 EP 548 DI 10.1007/s00125-014-3459-6 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CA9LD UT WOS:000349244100015 PM 25476525 ER PT J AU Xiao, F Fofana, I Thumann, C Mailly, L Alles, R Robinet, E Meyer, N Schaeffer, M Habersetzer, F Doffoel, M Leyssen, P Neyts, J Zeisel, MB Baumert, TF AF Xiao, Fei Fofana, Isabel Thumann, Christine Mailly, Laurent Alles, Roxane Robinet, Eric Meyer, Nicolas Schaeffer, Mickael Habersetzer, Francois Doffoel, Michel Leyssen, Pieter Neyts, Johan Zeisel, Mirjam B. Baumert, Thomas F. TI Synergy of entry inhibitors with direct-acting antivirals uncovers novel combinations for prevention and treatment of hepatitis C SO GUT LA English DT Article ID GENOTYPE 1 INFECTION; TREATMENT-NAIVE PATIENTS; VIRUS-CELL ENTRY; LIVER-TRANSPLANTATION; INTERFERON-ALPHA; FUTURE THERAPIES; PHASE-2 TRIAL; DOUBLE-BLIND; LUNG-CANCER; VIRAL ENTRY AB Objective Although direct-acting antiviral agents (DAAs) have markedly improved the outcome of treatment in chronic HCV infection, there continues to be an unmet medical need for improved therapies in difficult-to-treat patients as well as liver graft infection. Viral entry is a promising target for antiviral therapy. Design Aiming to explore the role of entry inhibitors for future clinical development, we investigated the antiviral efficacy and toxicity of entry inhibitors in combination with DAAs or other host-targeting agents (HTAs). Screening a large series of combinations of entry inhibitors with DAAs or other HTAs, we uncovered novel combinations of antivirals for prevention and treatment of HCV infection. Results Combinations of DAAs or HTAs and entry inhibitors including CD81-, scavenger receptor class B type I (SR-BI)-or claudin-1 (CLDN1)-specific antibodies or small-molecule inhibitors erlotinib and dasatinib were characterised by a marked and synergistic inhibition of HCV infection over a broad range of concentrations with undetectable toxicity in experimental designs for prevention and treatment both in cell culture models and in human liver-chimeric uPA/SCID mice. Conclusions Our results provide a rationale for the development of antiviral strategies combining entry inhibitors with DAAs or HTAs by taking advantage of synergy. The uncovered combinations provide perspectives for efficient strategies to prevent liver graft infection and novel interferon-free regimens. C1 [Xiao, Fei; Fofana, Isabel; Thumann, Christine; Mailly, Laurent; Alles, Roxane; Robinet, Eric; Habersetzer, Francois; Doffoel, Michel; Zeisel, Mirjam B.; Baumert, Thomas F.] INSERM, U1110, Strasbourg, France. [Xiao, Fei; Fofana, Isabel; Thumann, Christine; Mailly, Laurent; Alles, Roxane; Robinet, Eric; Habersetzer, Francois; Doffoel, Michel; Zeisel, Mirjam B.; Baumert, Thomas F.] Univ Strasbourg, Strasbourg, France. [Alles, Roxane] INSERM, U977, Strasbourg, France. [Meyer, Nicolas; Schaeffer, Mickael] Ctr Hosp Reg Univ Strasbourg, Strasbourg, France. [Habersetzer, Francois; Doffoel, Michel; Baumert, Thomas F.] Hop Univ Strasbourg, Strasbourg, France. [Leyssen, Pieter; Neyts, Johan] KULeuven, Rega Inst Med Res, Leuven, Belgium. [Baumert, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. RP Baumert, TF (reprint author), Univ Strasbourg, Inserm U1110, 3 Rue Koeberle, F-67000 Strasbourg, France. EM Thomas.Baumert@unistra.fr RI Zeisel, Mirjam/E-9205-2016; OI Zeisel, Mirjam/0000-0003-1606-0131; Eric, ROBINET/0000-0001-9765-805X FU Inserm; University of Strasbourg; European Union [ERC-2008-AdG-233130-HEPCENT]; European Union (INTERREG-IV-Rhin Superieur-FEDER-Hepato-Regio-Net); European Union (EU FP7 HepaMab); ANRS [2011/132, 2012/239, 2012/318, 2013/108]; Laboratoire d'excellence LabEx HEPSYS (Investissement d'Avenir) [ANR-10-LAB-28]; Institut Hospitalo-Universitaire Mix-Surg; Direction Generale de l'Offre de Soins [A12027MS]; French National Research Agency; Fund for Scientific Research (FWO) [G.0728.09N]; KULeuven GOA [10/014] FX This work was supported by Inserm, University of Strasbourg, the European Union (ERC-2008-AdG-233130-HEPCENT, INTERREG-IV-Rhin Superieur-FEDER-Hepato-Regio-Net 2009 and 2012, EU FP7 HepaMab), ANRS (2011/132, 2012/239, 2012/318, 2013/108), Laboratoire d'excellence LabEx HEPSYS (Investissement d'Avenir; ANR-10-LAB-28), the Institut Hospitalo-Universitaire Mix-Surg and the Direction Generale de l'Offre de Soins (A12027MS). This work has been published under the framework of the LABEX ANR-10-LABX-0028_HEPSYS and benefits from a funding from the state managed by the French National Research Agency as part of the investments for the future programme. The group in Leuven was funded by a grant from the Fund for Scientific Research (FWO) (G.0728.09N) and KULeuven GOA 10/014. NR 55 TC 26 Z9 27 U1 1 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD MAR PY 2015 VL 64 IS 3 BP 483 EP + DI 10.1136/gutjnl-2013-306155 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CB1GZ UT WOS:000349376600017 PM 24848265 ER PT J AU Robinson, ME Lindemer, ER Fonda, JR Milberg, WP McGlinchey, RE Salat, DH AF Robinson, Meghan E. Lindemer, Emily R. Fonda, Jennifer R. Milberg, William P. McGlinchey, Regina E. Salat, David H. TI Close-Range Blast Exposure is Associated With Altered Functional Connectivity in Veterans Independent of Concussion Symptoms at Time of Exposure SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; Veterans; blast injuries; traumatic brain injury; mild traumatic brain injury ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; GLOBAL SIGNAL REGRESSION; ADULT-RAT BRAIN; MILITARY PERSONNEL; INDUCED NEUROTRAUMA; COORDINATE SYSTEM; CORTICAL SURFACE; MOTOR CORTEX; NETWORKS AB Although there is emerging data on the effects of blast-related concussion (or mTBI) on cognition, the effects of blast exposure itself on the brain have only recently been explored. Toward this end, we examine functional connectivity to the posterior cingulate cortex, a primary region within the default mode network (DMN), in a cohort of 134 Iraq and Afghanistan Veterans characterized for a range of common military-associated comorbidities. Exposure to a blast at close range (<10 meters) was associated with decreased connectivity of bilateral primary somatosensory and motor cortices, and these changes were not different from those seen in participants with blast-related mTBI. These results remained significant when clinical factors such as sleep quality, chronic pain, or post traumatic stress disorder were included in the statistical model. In contrast, differences in functional connectivity based on concussion history and blast exposures at greater distances were not apparent. Despite the limitations of a study of this nature (e.g., assessments long removed from injury, self-reported blast history), these data demonstrate that blast exposure per se, which is prevalent among those who served in Iraq and Afghanistan, may be an important consideration in Veterans' health. It further offers a clinical guideline for determining which blasts (namely, those within 10 meters) are likely to lead to long-term health concerns and may be more accurate than using concussion symptoms alone. Hum Brain Mapp 36:911-922, 2015.Published 2014. This article is a U.S. Government work and is in the public domain in the USA. C1 [Robinson, Meghan E.; Lindemer, Emily R.; Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr NeRVe, Boston, MA 02130 USA. [Robinson, Meghan E.; Lindemer, Emily R.; Fonda, Jennifer R.; Milberg, William P.; McGlinchey, Regina E.; Salat, David H.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA 02130 USA. [Milberg, William P.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, GRECC, Boston, MA 02130 USA. [Salat, David H.] AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Robinson, ME (reprint author), VA Boston Healthcare Syst, TRACTS 182, 150 S Huntington Ave, Boston, MA 02130 USA. EM meghan.robinson@va.gov RI McGlinchey, Regina/R-1971-2016 FU Translational Research Center for TBI and Stress Disorders (TRACTS) VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B9254-C] FX Contract grant sponsor: Translational Research Center for TBI and Stress Disorders (TRACTS) VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence; Contract grant number: B9254-C (R.E.M. and W.P.M). NR 53 TC 12 Z9 12 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAR PY 2015 VL 36 IS 3 BP 911 EP 922 DI 10.1002/hbm.22675 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CB4QI UT WOS:000349612500008 PM 25366378 ER PT J AU Dai, WY Brisimi, TS Adams, WG Mela, T Saligrama, V Paschalidis, IC AF Dai, Wuyang Brisimi, Theodora S. Adams, William G. Mela, Theofanie Saligrama, Venkatesh Paschalidis, Ioannis Ch. TI Prediction of hospitalization due to heart diseases by supervised learning methods SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE Prevention; Predictive models; Hospitalization; Heart diseases; Machine learning; Electronic Health Records (EHRs) ID ELECTRONIC MEDICAL-RECORDS; PRIMARY-CARE; RISK AB Background: In 2008, the United States spent $2.2 trillion for healthcare, which was 15.5% of its GDP. 31% of this expenditure is attributed to hospital care. Evidently, even modest reductions in hospital care costs matter. A 2009 study showed that nearly $30.8 billion in hospital care cost during 2006 was potentially preventable, with heart diseases being responsible for about 31% of that amount. Methods: Our goal is to accurately and efficiently predict heart-related hospitalizations based on the available patient-specific medical history. To the best of our knowledge, the approaches we introduce are novel for this problem. The prediction of hospitalization is formulated as a supervised classification problem. We use de-identified Electronic Health Record (EHR) data from a large urban hospital in Boston to identify patients with heart diseases. Patients are labeled and randomly partitioned into a training and a test set. We apply five machine learning algorithms, namely Support Vector Machines (SVM), AdaBoost using trees as the weak learner, logistic regression, a naive Bayes event classifier, and a variation of a Likelihood Ratio Test adapted to the specific problem. Each model is trained on the training set and then tested on the test set. Results: All five models show consistent results, which could, to some extent, indicate the limit of the achievable prediction accuracy. Our results show that with under 30% false alarm rate, the detection rate could be as high as 82%. These accuracy rates translate to a considerable amount of potential savings, if used in practice. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Dai, Wuyang; Brisimi, Theodora S.; Saligrama, Venkatesh; Paschalidis, Ioannis Ch.] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. [Dai, Wuyang; Brisimi, Theodora S.; Saligrama, Venkatesh; Paschalidis, Ioannis Ch.] Boston Univ, Div Syst Engn, Boston, MA 02215 USA. [Adams, William G.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Adams, William G.] Boston Med Ctr, Boston, MA 02118 USA. [Mela, Theofanie] Massachusetts Gen Hosp, Arrhythmia Serv, Electrophysiol Lab, Boston, MA 02114 USA. RP Paschalidis, IC (reprint author), Boston Univ, Dept Elect & Comp Engn, 8 St Marys St, Boston, MA 02215 USA. EM yannisp@bu.edu OI Paschalidis, Ioannis/0000-0002-3343-2913 FU NSF [IIS-1237022, CNS-1239021]; NIH/NIGMS [GM093147]; ARO [W911NF-11-1-0227, W911NF-12-1-0390]; ONR [N0001410-1-0952] FX This research has been partially supported by the NSF under grants IIS-1237022 and CNS-1239021, by the NIH/NIGMS under grant GM093147, by the ARO under grants W911NF-11-1-0227 and W911NF-12-1-0390, and by the ONR under grant N0001410-1-0952. NR 21 TC 10 Z9 10 U1 6 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 EI 1872-8243 J9 INT J MED INFORM JI Int. J. Med. Inform. PD MAR PY 2015 VL 84 IS 3 BP 189 EP 197 DI 10.1016/j.ijmedinf.2014.10.002 PG 9 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA CB2PV UT WOS:000349471000003 PM 25497295 ER PT J AU Ebrahimzadeh, MH Birjandinejad, A Golhasani, F Moradi, A Vahedi, E Kachooei, AR AF Ebrahimzadeh, Mohammad H. Birjandinejad, Ali Golhasani, Farideh Moradi, Ali Vahedi, Ehsan Kachooei, Amir R. TI Cross-cultural adaptation, validation, and reliability testing of the Shoulder Pain and Disability Index in the Persian population with shoulder problems SO INTERNATIONAL JOURNAL OF REHABILITATION RESEARCH LA English DT Article DE Persian; psychometric; reliability; Shoulder Pain and Disability Index; validity ID VERSION; VALIDITY; TRANSLATION; GUIDELINES AB We aimed to validate the translated and cross-culturally adapted Persian version of the Shoulder Pain and Disability Index (SPADI). The final Persian SPADI was administered to 190 patients, out of whom 83 patients returned for the retest. We administered the Persian version of the SF-36 quality-of-life inventory and the disabilities of the arm shoulder and hand (DASH) questionnaires at the first visit to assess the convergent validity. Cronbach's alpha was 0.94 for the total SPADI, which showed excellent internal consistency. The intraclass correlation coefficient was 0.84 for the total SPADI, which showed good reliability between the test and retest. Convergent validity was confirmed, as the Spearman correlation between total SPADI and DASH was 0.61. Moreover, there was significant correlation between the subscales of the SPADI and SF-36 scales. The Persian version of the SPADI proved to be a reliable and valid instrument to be implemented in the Persian population with shoulder disorders. Level of evidence: level II. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Ebrahimzadeh, Mohammad H.; Birjandinejad, Ali; Golhasani, Farideh; Moradi, Ali; Vahedi, Ehsan; Kachooei, Amir R.] Mashhad Univ Med Sci, Orthoped Res Ctr, Mashhad, Iran. [Kachooei, Amir R.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Kachooei, AR (reprint author), Yawkey Bldg,55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM akachooei@mgh.harvard.edu NR 12 TC 4 Z9 4 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0342-5282 EI 1473-5660 J9 INT J REHABIL RES JI Int. J. Rehabil. Res. PD MAR PY 2015 VL 38 IS 1 BP 84 EP 87 DI 10.1097/MRR.0000000000000088 PG 4 WC Rehabilitation SC Rehabilitation GA CB1NY UT WOS:000349395900012 PM 25305009 ER PT J AU Bryant, MS Workman, CD Jackson, GR AF Bryant, Mon S. Workman, Craig D. Jackson, George R. TI Multidirectional walk test in individuals with Parkinson's disease: a validity study SO INTERNATIONAL JOURNAL OF REHABILITATION RESEARCH LA English DT Article DE backward walk; forward walk; GAITRite; Parkinson's disease; sideways walk; validity ID GAIT ASSESSMENT; RELIABILITY; SYSTEM; PARAMETERS AB Gait parameters of forward, backward, and sideways walk were studied when the participants walked overground in four directions at their self-selected speed and were compared with walking in the four directions on an instrumented GAITRite walkway. Intraclass correlation coefficients between the overground walk test measures and the instrumented walkway measures of gait speed, cadence, and stride length for the forward walk were 0.85, 0.88, and 0.87, respectively. For the backward walk, the coefficients were 0.91 for gait speed, 0.75 for cadence, and 0.93 for stride length. For the sideways walk, the coefficients were 0.92 for gait speed, 0.93 for cadence, and 0.94 for stride length. Gait parameters of forward, backward, and sideways walk obtained by the overground walk test had excellent agreement with those obtained by the instrumented walkway. The quick timed test provided quantitative data for gait evaluation and was valid for clinical use. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Bryant, Mon S.; Workman, Craig D.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Res Serv, Houston, TX 77030 USA. [Bryant, Mon S.] Univ Houston, Dept Phys Med & Rehabil, Houston, TX USA. [Workman, Craig D.] Univ Houston, Dept Hlth & Human Performance, Houston, TX USA. [Jackson, George R.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Houston, TX 77030 USA. [Jackson, George R.] Baylor Coll Med, Houston, TX 77030 USA. RP Bryant, MS (reprint author), Michael E DeBakey VA Med Ctr, Res Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM msbryant@bcm.edu FU RRD VA [IK2 RX000734] NR 17 TC 1 Z9 1 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0342-5282 EI 1473-5660 J9 INT J REHABIL RES JI Int. J. Rehabil. Res. PD MAR PY 2015 VL 38 IS 1 BP 88 EP 91 DI 10.1097/MRR.0000000000000091 PG 4 WC Rehabilitation SC Rehabilitation GA CB1NY UT WOS:000349395900013 PM 25371075 ER PT J AU Zheng, B Fisher, DE AF Zheng, Bin Fisher, David E. TI Metabolic Vulnerability in Melanoma: A ME2 (Me Too) Story SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID MALIC ENZYMES; SENESCENCE AB Metabolic reprograming is a hallmark of cancer and might represent an Achilles' heel in cancer cells. The study by Chang et al. in this issue highlights a critical role of mitochondrial malic enzyme 2 (ME2) in melanoma progression. Targeting ME2 could be an effective approach to inhibit melanoma cell proliferation and tumor growth. C1 [Zheng, Bin; Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Boston, MA 02129 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Boston, MA 02129 USA. EM dfisher3@mgh.harvard.edu FU NCI NIH HHS [R01 CA166717, P01 CA163222]; NIAMS NIH HHS [R01 AR043369] NR 11 TC 1 Z9 1 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2015 VL 135 IS 3 BP 657 EP 659 DI 10.1038/jid.2014.449 PG 3 WC Dermatology SC Dermatology GA CB2AH UT WOS:000349428600005 PM 25666673 ER PT J AU Marneros, AG AF Marneros, Alexander G. TI Genetics of Aplasia Cutis Reveal Novel Regulators of Skin Morphogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Review ID ADAMS-OLIVER SYNDROME; LINKED-N-ACETYLGLUCOSAMINE; TRANSCRIPTION FACTOR AP-2; RIBOSOME BIOGENESIS; CELL-PROLIFERATION; NOTCH RECEPTORS; LIMB ANOMALIES; MUTATIONS; DIFFERENTIATION; EPIDERMIS AB The molecular mechanisms that control skin morphogenesis are complex and only incompletely understood. Aplasia cutis manifests with localized skin defects at birth and is a feature in various syndromes. Identifying the genes that cause these genetic skin conditions provides the opportunity to define novel regulators of skin morphogenesis. Recently, human genetic approaches have led to the identification of aplasia cutis causing mutations in genes that have previously not been implicated to have an important role in skin biology. These findings reveal novel molecular mechanisms that are involved in skin formation during development. C1 [Marneros, Alexander G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA USA. RP Marneros, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, CNY 149,Room 3-216,13th St, Charlestown, MA 02129 USA. EM amarneros@mgh.harvard.edu NR 43 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2015 VL 135 IS 3 BP 666 EP 672 DI 10.1038/jid.2014.413 PG 7 WC Dermatology SC Dermatology GA CB2AH UT WOS:000349428600008 PM 25355129 ER PT J AU Dias, MF Riboldi, M Seco, J Castelhano, I Pella, A Mirandola, A Peralta, L Ciocca, M Orecchia, R Baroni, G AF Dias, Marta F. Riboldi, Marco Seco, Joao Castelhano, Ines Pella, Andrea Mirandola, Alfredo Peralta, Luis Ciocca, Mario Orecchia, Roberto Baroni, Guido TI Scan path optimization with/without clustering for active beam delivery in charged particle therapy SO PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS LA English DT Article DE Scan path; Optimization algorithms; Path length; Transit particles; Wasted particles AB Purpose: To compare different algorithms to optimize the scanning path in charged particle therapy with quasidiscrete scanning. We implemented a Hybrid Genetic Algorithm with Heuristics (HyGA) and combined it with clustering techniques. The performance was compared to Simulated Annealing (SA) and to commercially available treatment planning system (TPS). Methods: Performance and clinical implications were assessed using data from 10 patients treated at CNAO (Centro Nazionale di Adroterapia Oncologica). Clinical treatments are performed relying on beam deflection, avoiding irradiation for transitions between adjacent spots larger than 2 cm. A clustering method was implemented with HyGA (HyGA_Cl), which assumes beam deflection during transition between clusters. Clinical performance was determined as the total number of particles delivered during spot transitions and the number of particles wasted due to beam deflection. Results were compared to scan paths obtained with CNAO TPS. Results: SA and HyGA produced on average shorter paths compared to the currently available TPS. This did not result in a reduction of transit particles, due to the concomitant effect of beam deflection out of the extraction line. HyGA_Cl achieved 2% average reduction in transit particles when compared to CNAO TPS. As a drawback, wasted particles increased, due to more frequent use of beam deflection. Both the SA and HyGA algorithms reduced the number of wasted particles. Conclusion: SA and HyGA proved to be the most cost-effective methods in reducing wasted particles, with benefits in terms of shorter scan paths. A decrease in transit particles delivered with beam deflection can be achieved using HyGA_Cl. (C) 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. C1 [Dias, Marta F.; Peralta, Luis] Univ Lisbon, Fac Sci, Dept Phys, P-1749 Lisbon, Portugal. [Dias, Marta F.; Peralta, Luis] Lab Instrumentacao & Fis Particulas, P-1749 Lisbon, Portugal. [Dias, Marta F.; Riboldi, Marco; Castelhano, Ines; Pella, Andrea; Baroni, Guido] Politecn Milan, Dipartimento Elettron Informaz & Bioingn, I-20133 Milan, Italy. [Riboldi, Marco; Baroni, Guido] Ctr Nazl Adroterapia Oncol, Bioengn Unit, I-27100 Pavia, Italy. [Seco, Joao] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Castelhano, Ines] Univ Lisbon, Inst Biophys & Biomed Engn, Fac Sci, P-1749 Lisbon, Portugal. [Mirandola, Alfredo; Ciocca, Mario] Ctr Nazl Adroterapia Oncol, I-27100 Pavia, Italy. [Orecchia, Roberto] Ctr Nazl Adroterapia Oncol, Dept Med, I-27100 Pavia, Italy. [Orecchia, Roberto] European Inst Oncol, Adv Radiotherapy Ctr, Div Radiotherapy, I-20141 Milan, Italy. [Orecchia, Roberto] Univ Milan, Dept Sci & Biomed Technol, I-20122 Milan, Italy. RP Dias, MF (reprint author), 88 Fairview Ave, Belmont, MA 02478 USA. EM marta.dias@mail.polimi.it RI Peralta, Luis/C-8369-2011; Riboldi, Marco/I-2980-2014 OI Peralta, Luis/0000-0002-3834-1762; Mirandola, Alfredo/0000-0003-2427-2329; Riboldi, Marco/0000-0002-2431-4966 FU LLP/Erasmus Grant FX The work was partially supported by the LLP/Erasmus Grant. NR 12 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1120-1797 EI 1724-191X J9 PHYS MEDICA JI Phys. Medica PD MAR PY 2015 VL 31 IS 2 BP 130 EP 136 DI 10.1016/j.ejmp.2015.01.001 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CB3TS UT WOS:000349552400003 PM 25616862 ER PT J AU Street, AE Gilman, SE Rosellini, AJ Stein, MB Bromet, EJ Cox, KL Colpe, LJ Fullerton, CS Gruber, MJ Heeringa, SG Lewandowski-Romps, L Little, RJA Naifeh, JA Nock, MK Sampson, NA Schoenbaum, M Ursano, RJ Zaslavsky, AM Kessler, RC AF Street, A. E. Gilman, S. E. Rosellini, A. J. Stein, M. B. Bromet, E. J. Cox, K. L. Colpe, L. J. Fullerton, C. S. Gruber, M. J. Heeringa, S. G. Lewandowski-Romps, L. Little, R. J. A. Naifeh, J. A. Nock, M. K. Sampson, N. A. Schoenbaum, M. Ursano, R. J. Zaslavsky, A. M. Kessler, R. C. CA Army STARRS Collaborators TI Understanding the elevated suicide risk of female soldiers during deployments SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Army; Army STARRS; epidemiology; gender; military; risk factors; suicide ID SERVICEMEMBERS ARMY STARRS; MENTAL-HEALTH; GENDER-DIFFERENCES; OEF/OIF VETERANS; UNITED-STATES; US ARMY; MILITARY PERSONNEL; COMBAT DEPLOYMENT; SEXUAL-HARASSMENT; RESILIENCE AB Background. The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment. Method. Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004-2009 (n = 975 057) were used to characterize the gender x deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier's occupation, the proportion of same-gender soldiers in each soldier's unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier's pre-deployment history of treated mental/behavioral disorders. Results. The suicide rate of currently deployed women (14.0/100 000 person-years) was 3.1-3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100 000 personyears) was 0.9-1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female: male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1-6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9-2.8) after adjusting for the hypothesized explanatory variables. Conclusions. These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women. C1 [Street, A. E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Street, A. E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gilman, S. E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Gilman, S. E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rosellini, A. J.; Gruber, M. J.; Sampson, N. A.; Zaslavsky, A. M.; Kessler, R. C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Stein, M. B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Stein, M. B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Stein, M. B.] VA San Diego Healthcare Syst, San Diego, CA USA. [Bromet, E. J.] SUNY Stony Brook, Sch Med, Dept Psychiat, Stony Brook, NY 11794 USA. [Cox, K. L.] US Army Publ Hlth Command, Aberdeen Proving Ground, MD USA. [Colpe, L. J.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Fullerton, C. S.; Naifeh, J. A.; Ursano, R. J.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Sch Med, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [Heeringa, S. G.; Lewandowski-Romps, L.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Little, R. J. A.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Nock, M. K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Schoenbaum, M.] NIMH, Off Sci Policy Planning & Commun, Bethesda, MD 20892 USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM kessler@hcp.med.harvard.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU Department of the Army; US Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIH/NIMH) [U01MH087981] FX Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement number U01MH087981 with the US Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIH/NIMH). The contents are solely the responsibility of the authors and do not necessarily represent the views of the Department of Health and Human Services, NIMH, the Department of the Army, or the DoD. Co-principal investigators are: Robert J. Ursano, MD (Uniformed Services University of the Health Sciences) and Murray B. Stein, MD, MPH (University of California San Diego and VA San Diego Healthcare System). Site principal investigators are: Steven Heeringa, PhD (University of Michigan) and Ronald C. Kessler, PhD (Harvard Medical School). NIMH collaborating scientists are: Lisa J. Colpe, PhD, MPH and Michael Schoenbaum, PhD. Army liaisons/consultants are: Col. Steven Cersovsky, MD, MPH (US Army Public Health Command; USAPHC); Kenneth Cox, MD, MPH (USAPHC). Other team members: Pablo A. Aliaga, MA (Uniformed Services University of the Health Sciences); Col. David M. Benedek, MD (Uniformed Services University of the Health Sciences); Susan Borja, PhD (NIMH); Gregory G. Brown, PhD (University of California San Diego); Laura Campbell-Sills, PhD (University of California San Diego); Catherine L. Dempsey, PhD, MPH (Uniformed Services University of the Health Sciences); Richard Frank, PhD (Harvard Medical School); Carol S. Fullerton, PhD (Uniformed Services University of the Health Sciences); Nancy Gebler, MA (University of Michigan); Robert K. Gifford, PhD (Uniformed Services University of the Health Sciences); Stephen E. Gilman, ScD (Harvard School of Public Health); Marjan G. Holloway, PhD (Uniformed Services University of the Health Sciences); Paul E. Hurwitz, MPH (Uniformed Services University of the Health Sciences); Sonia Jain, PhD (University of California San Diego); Tzu-Cheg Kao, PhD (Uniformed Services University of the Health Sciences); Karestan C. Koenen, PhD (Columbia University); Lisa Lewandowski-Romps, PhD (University of Michigan); Holly Herberman Mash, PhD (Uniformed Services University of the Health Sciences); James E. McCarroll, PhD, MPH (Uniformed Services University of the Health Sciences); Katie A. McLaughlin, PhD (Harvard Medical School); James A. Naifeh, PhD (Uniformed Services University of the Health Sciences); Matthew K. Nock, PhD (Harvard University); Rema Raman, PhD (University of California San Diego); Sherri Rose, PhD (Harvard Medical School); Anthony Joseph Rosellini, PhD (Harvard Medical School); Nancy A. Sampson, BA (Harvard Medical School); LCDR Patcho Santiago, MD, MPH (Uniformed Services University of the Health Sciences); Michaelle Scanlon, MBA (NIMH); Jordan Smoller, MD, ScD (Harvard Medical School); Michael L. Thomas, PhD (University of California San Diego); Patti L. Vegella, MS, MA (Uniformed Services University of the Health Sciences); Christina Wassel, PhD (University of Pittsburgh); and Alan M. Zaslavsky, PhD (Harvard Medical School). A complete list of Army STARRS publications can be found at http://www.ARMYSTARRS.org. As a cooperative agreement, scientists employed by NIMH (L. J. Colpe and M. Schoenbaum) and Army liaisons/consultants (Col. Steven Cersovsky, MD, MPH USAPHC and Kenneth Cox, MD, MPH USAPHC) collaborated to develop the study protocol and data collection instruments, supervise data collection, plan and supervise data analyses, interpret results, and prepare reports.; Although a draft of this manuscript was submitted to the Army and NIMH for review and comment prior to submission, this was with the understanding that comments would be no more than advisory. NR 46 TC 9 Z9 9 U1 4 U2 18 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD MAR PY 2015 VL 45 IS 4 BP 717 EP 726 DI 10.1017/S003329171400258X PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CB4SR UT WOS:000349618900004 PM 25359554 ER PT J AU Balbale, SN Turcios, S LaVela, SL AF Balbale, Salva Najib Turcios, Stephanie LaVela, Sherri L. TI Health Care Employee Perceptions of Patient-Centered Care SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE health care; health care professionals; photography; photovoice; quality improvement; research; qualitative ID PHOTOVOICE; OUTCOMES; SATISFACTION; QUALITY; TRANSFORMATION; EMPOWERMENT; EXPERIENCE; PROMOTION; SYSTEM; NEEDS AB Given the importance of health care employees in the delivery of patient-centered care, understanding their unique perspectives is essential for quality improvement. The purpose of this study was to use photovoice to evaluate perceptions and experiences around patient-centered care among U.S. Veterans Affairs (VA) health care employees. We asked participants to take photographs of salient features in their environment related to patient-centered care. We used the photographs to facilitate dialogue during follow-up interviews. Twelve VA health care employees across two VA sites participated in the project. Although most participants felt satisfied with their work environment and experiences at the VA, they identified several areas for improvement. These included a need for more employee health and wellness initiatives and a need for enhanced opportunities for training and professional growth. Application of photovoice enabled us to learn about employees' unique perspectives around patient-centered care while engaging them in an evaluation of care delivery. C1 [Balbale, Salva Najib; Turcios, Stephanie; LaVela, Sherri L.] US Dept Vet Affairs, Ctr Evaluat Practices & Experiences Patient Ctr C, Hines, IL USA. RP Balbale, SN (reprint author), Edward Hines Jr VA Hosp, 5000 S 5th Ave 151H, Hines, IL 60141 USA. EM Salva.Balbale@va.gov FU HSRD VA [I50 HX001171] NR 34 TC 3 Z9 3 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 EI 1552-7557 J9 QUAL HEALTH RES JI Qual. Health Res. PD MAR PY 2015 VL 25 IS 3 BP 417 EP 425 DI 10.1177/1049732314553011 PG 9 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA CB1FO UT WOS:000349372600011 PM 25274626 ER PT J AU Kelley, PW Kenny, DJ Gordon, DR Benner, P AF Kelley, Patricia Watts Kenny, Deborah J. Gordon, Deborah R. Benner, Patricia TI The Evolution of Case Management for Service Members Injured in Iraq and Afghanistan SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE brain injury; caregivers; caregiving; discharge planning; health care; managed; interpretative phenomenological analysis (IPA); posttraumatic stress disorder (PTSD); rehabilitation; trauma; war; victims of ID CARE AB In this article we describe the nursing care needs of wounded service members (WSMs) from the wars in Iraq and Afghanistan and the evolving role of the nurse case manager (CM). New types of injuries, in-field treatment, immediate transport to multiple care centers, and new technologies have created a new patient population of WSMs that requires new types of nursing care and knowledge. We interviewed 235 nurses, including CMs from nine military treatment facilities (MTFs) and the Veterans Administration (VA), on actual patient care experiences and new knowledge development, and 67 WSMs about their experiences of care. New military and VA nurse case management roles are essential for the effective functioning of the evolving, highly specialized, and transport-based health care system. Working effectively with WSMs required that the CM role be expanded beyond health care management to include family support, re-entry, and life coaching for the extremely altered life circumstances of WSMs. C1 [Kelley, Patricia Watts] US Dept Vet Affairs, Washington, DC 20420 USA. [Kenny, Deborah J.] Univ Colorado, Beth El Coll Nursing & Hlth Sci, Colorado Springs, CO 80907 USA. [Gordon, Deborah R.; Benner, Patricia] Univ Calif San Francisco, Dept Anthropol Hist & Social Med, San Francisco, CA 94143 USA. [Benner, Patricia] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. RP Kelley, PW (reprint author), US Dept Vet Affairs, Off Res & Dev Hlth Serv Res & Dev, 810 Vermont Ave NW, Washington, DC 20420 USA. EM Patricia.kelley2@va.gov NR 19 TC 0 Z9 0 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 EI 1552-7557 J9 QUAL HEALTH RES JI Qual. Health Res. PD MAR PY 2015 VL 25 IS 3 BP 426 EP 439 DI 10.1177/1049732314553228 PG 14 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA CB1FO UT WOS:000349372600012 PM 25288405 ER PT J AU Chang, CY Gill, CM Huang, AJ Simeone, FJ Torriani, M McCarthy, JC Bredella, MA AF Chang, Connie Y. Gill, Corey M. Huang, Ambrose J. Simeone, Frank J. Torriani, Martin McCarthy, Joseph C. Bredella, Miriam A. TI Use of MR arthrography in detecting tears of the ligamentum teres with arthroscopic correlation SO SKELETAL RADIOLOGY LA English DT Article DE (Maximum 5)-hip; Ligamentum teres; MR arthrography; Arthroscopy ID HIP PAIN; PREVALENCE AB To demonstrate the normal appearance of the ligamentum teres on MR arthrography (MRA) and evaluate the accuracy of MRA in detecting ligamentum teres tears with arthroscopic correlation. Institutional Review Board approval was obtained with a waiver for informed consent because of the retrospective study design. A total of 165 cases in 159 patients (111 females, 48 males; mean age 41 +/- 12 years) who underwent both MRA and hip arthroscopy were evaluated for appearance of the ligamentum teres, including the size, number of bundles, and ligamentum teres tears. Marrow edema of the fovea capitis adjacent to the ligamentum teres insertion and the presence of hip plicae were also recorded. The mean thickness and length of the ligamentum teres were 3.5 +/- 1.5 mm and 25.2 +/- 3.8 mm, respectively. Sensitivity, specificity, positive and negative predictive value, and accuracy of MRA for the detection of ligamentum teres tears were 78, 97, 74, 97, and 95 %, respectively. MRA is an accurate method to evaluate the normal morphology and to detect tears of the ligamentum teres. C1 [Chang, Connie Y.; Gill, Corey M.; Huang, Ambrose J.; Simeone, Frank J.; Torriani, Martin; Bredella, Miriam A.] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. [McCarthy, Joseph C.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. RP Chang, CY (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM cychang@mgh.harvard.edu; jcmccarthy1@partners.org NR 22 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAR PY 2015 VL 44 IS 3 BP 361 EP 367 DI 10.1007/s00256-014-2082-4 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CA5CM UT WOS:000348925400007 PM 25527467 ER PT J AU Taneja, AK Miranda, FC Braga, CAP Gill, CM Hartmann, LGC Santos, DCB Rosemberg, LA AF Taneja, Atul K. Miranda, Frederico C. Braga, Cesar A. P. Gill, Corey M. Hartmann, Luiz G. C. Santos, Durval C. B. Rosemberg, Laercio A. TI MRI features of the anterolateral ligament of the knee SO SKELETAL RADIOLOGY LA English DT Article DE Knee; Anatomy; Anterolateral ligament; Lateral collateral ligament; Segond; MRI ID SEGOND-FRACTURE; ILIOTIBIAL TRACT; ANATOMY AB Evaluate the visibility and describe the anatomical features of the anterolateral ligament of the knee using MRI. Magnetic resonance imaging examinations of the knee were independently reviewed by two musculoskeletal radiologists and assessed for the visibility of the anterolateral ligament under direct cross-referencing of axial and coronal images as complete, partial, or non-visible. Distal insertion site (tibial, meniscal), distance to lateral tibial plateau, measurements (length, width, thickness), and associated imaging findings were also tabulated. Clinical and surgical records were also reviewed. Seventy MRI scans from 60 consecutive subjects were included in the study. Mean age was 40 years, body mass 74.9 kg, and height 1.72 m. The subject population was 53 % male, most of the knees were from the left side (51 %), and chronic pain was the main clinical symptom (40 %). Nine knees (13 %) had undergone previous surgery. The anterolateral ligament was identified in 51 % of the knees: completely visible in 11 % and partially visible in 40 %. In all visible cases, the distal insertion site was identified on the tibia, with a mean distance of 5.7 mm to the plateau. A completely visible ligament had a mean length of 33.2 mm, thickness of 5.6 mm, and width of 1.9 mm. Inter-observer agreement for ligament presence was significant (kappa = 0.7). Statistical analyses showed a trend to be more visible in men, with a longer length compared with women. Magnetic resonance imaging clearly identifies the anterolateral ligament of the knee in slightly more than half of cases, being partially visible in most of them. In all cases, a tibial insertion is characterized. C1 [Taneja, Atul K.; Miranda, Frederico C.; Braga, Cesar A. P.; Hartmann, Luiz G. C.; Santos, Durval C. B.; Rosemberg, Laercio A.] Hosp Israelita Albert Einstein, Dept Imaging, Musculoskeletal Radiol Div, Sao Paulo, Brazil. [Taneja, Atul K.] Hosp Coracao HCor, Ctr Diagnost, Sao Paulo, Brazil. [Taneja, Atul K.] Teleimagem, Sao Paulo, Brazil. [Gill, Corey M.] Massachusetts Gen Hosp, Dept Neurol, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Gill, Corey M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Gill, Corey M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Taneja, AK (reprint author), Hosp Israelita Albert Einstein, Dept Imaging, Musculoskeletal Radiol Div, Ave Albert Einstein 627, Sao Paulo, Brazil. EM taneja@einstein.br RI Taneja, Atul/N-3133-2014 OI Taneja, Atul/0000-0002-4655-2033 NR 14 TC 19 Z9 19 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAR PY 2015 VL 44 IS 3 BP 403 EP 410 DI 10.1007/s00256-014-2052-x PG 8 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CA5CM UT WOS:000348925400012 PM 25427785 ER PT J AU Taneja, AK Miranda, FC Braga, CAP Gill, CM Hartmann, LGC Santos, DCB Rosemberg, LA AF Taneja, Atul K. Miranda, Frederico C. Braga, Cesar A. P. Gill, Corey M. Hartmann, Luiz G. C. Santos, Durval C. B. Rosemberg, Laercio A. TI MRI features of the anterolateral ligament of the knee (vol 44, pg 403, 2015) SO SKELETAL RADIOLOGY LA English DT Correction C1 [Taneja, Atul K.; Miranda, Frederico C.; Braga, Cesar A. P.; Hartmann, Luiz G. C.; Santos, Durval C. B.; Rosemberg, Laercio A.] Hosp Israelita Albert Einstein, Dept Imaging, Musculoskeletal Radiol Div, Sao Paulo, Brazil. [Taneja, Atul K.] Hosp Coracao HCor, Ctr Diagnost, Sao Paulo, Brazil. [Taneja, Atul K.] Teleimagem, Sao Paulo, Brazil. [Gill, Corey M.] Massachusetts Gen Hosp, Dept Neurol, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Gill, Corey M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Gill, Corey M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Taneja, AK (reprint author), Hosp Israelita Albert Einstein, Dept Imaging, Musculoskeletal Radiol Div, Ave Albert Einstein 627, Sao Paulo, Brazil. EM taneja@einstein.br RI Taneja, Atul/N-3133-2014 OI Taneja, Atul/0000-0002-4655-2033 NR 1 TC 2 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAR PY 2015 VL 44 IS 3 BP 411 EP 411 DI 10.1007/s00256-014-2086-0 PG 1 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CA5CM UT WOS:000348925400013 PM 25520243 ER PT J AU Sheu, EG Nau, P Nath, B Kuo, B Rattner, DW AF Sheu, Eric G. Nau, Peter Nath, Barbara Kuo, Braden Rattner, David W. TI A comparative trial of laparoscopic magnetic sphincter augmentation and Nissen fundoplication SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-American-Gastrointestinal-and-Endoscopic-Surgeons (SAGES) CY APR 02-05, 2014 CL Salt Lake City, UT SP Soc Amer Gastrointestinal & Endoscop Surg DE Gastroesophageal reflux disease; Fundoplication; LINX; Magnetic sphincter augmentation; Dysphagia; Endoscopic dilation ID GASTROESOPHAGEAL-REFLUX DISEASE; ANTIREFLUX SURGERY; CLINICAL-TRIAL AB Laparoscopic magnetic sphincter augmentation (MSA) with the LINX device is a promising new therapy for the treatment of gastroesophageal reflux disease (GERD). Initial studies have demonstrated MSA to be safe and effective. However, no direct comparison between MSA and laparoscopic Nissen fundoplication (LNF), the gold standard surgical therapy for GERD, has been performed. A single institution, case-control study was conducted of MSA performed from 2012 to 2013 and a cohort of LNF matched for age, gender, and hiatal hernia size. MSA and LNF were both effective treatments for reflux with 75 and 83 % of patients, respectively, reporting resolution of GERD at short-term follow-up. Dysphagia was common following both MSA and LNF, but severe dysphagia requiring endoscopic dilation was more frequent after MSA (50 vs. 0 %, p = 0.01). Need for dilation did not correlate with size of the LINX device or any other examined patient factors. A trend toward decreased adverse GI symptoms of bloating, flatulence, and diarrhea was seen after MSA compared to LNF (0 vs. 33 %). MSA had a shorter operative time (64 vs. 90 min, p < 0.01) but other peri-operative outcomes, including pain, morbidity, and re-admissions were equivalent to LNF. MSA patients were more likely to be self-referred (58 vs. 0 %, p < 0.001). MSA and LNF are both effective and safe treatments for GERD; however, severe dysphagia requiring endoscopic intervention is more common with MSA. Other adverse GI side effects may be less frequent after MSA. Consideration should be paid to these distinct post-operative symptom profiles when selecting a surgical therapy for reflux disease. C1 [Sheu, Eric G.; Rattner, David W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sheu, Eric G.; Rattner, David W.] Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA USA. [Nau, Peter] Univ Iowa, Dept Surg, Iowa City, IA 52242 USA. [Nath, Barbara; Kuo, Braden] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM esheu@partners.org; drattner@mgh.harvard.edu NR 12 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD MAR PY 2015 VL 29 IS 3 BP 505 EP 509 DI 10.1007/s00464-014-3704-6 PG 5 WC Surgery SC Surgery GA CB0DU UT WOS:000349296400001 PM 25012804 ER PT J AU Bordeianou, L Sylla, P Kinnier, CV Rattner, D AF Bordeianou, Liliana Sylla, Patricia Kinnier, Christine V. Rattner, David TI Perineal sigmoidopexy utilizing transanal endoscopic microsurgery (TEM) to treat full thickness rectal prolapse: a feasibility trial in porcine and human cadaver models SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Bowel; Surgical; Perineal rectosigmoidectomy; Rectal prolapse; Transanal endoscopic microsurgery; Cadaver model ID EXPRESS PROCEDURE; INVASIVE SURGERY; MANAGEMENT; SUSPENSION; EVOLUTION; FIXATION; REPAIR AB Perineal approaches for rectal prolapse repair have low complication rates but high recurrence rates, while abdominal approaches that include sigmoidopexy have lower recurrence rates but higher complication rates. To optimize both recurrence and complication rates, we developed a novel procedure that uses transanal endoscopic microsurgery (TEM) to perform a sigmoidopexy via a perineal approach. We created a rectal prolapse model in six swine and two human cadavers using a previously published technique. The rectum was mobilized and eviscerated transanally. After marking the planned point of sigmoid transection, the rectum was returned to the peritoneal cavity. A TEM proctoscope was inserted transanally alongside the rectum, and the lateral sigmoid colon walls were sutured to the sacrum. The sigmoid colon was then transected where previously planned, and a primary sigmoid anastomosis was performed. Total operative time, sigmoidopexy operative time, and suture security were measured and compared to standard rectosigmoidectomy and abdominal sigmoidopexy times. No sigmoid colon, iliac vessel, bladder, or ureteral injuries occurred. At least two sigmoidopexy sutures were secure on inspection in all animals and human cadavers, with increasing success of secure suture placement as experience increased. Operative length was similar to traditional abdominal sigmoidopexy. TEM sigmoidopexy is technically feasible. This approach has the potential to reduce the recurrence rate associated with perineal approaches alone, but further study is needed to confirm this hypothesis. C1 [Bordeianou, Liliana; Sylla, Patricia; Kinnier, Christine V.; Rattner, David] Massachusetts Gen Hosp, Pelv Floor Disorders Ctr, Div Gastrointestinal Surg, Boston, MA 02114 USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Pelv Floor Disorders Ctr, Div Gastrointestinal Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@mgh.harvard.edu; ckinnier@partners.org NR 20 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD MAR PY 2015 VL 29 IS 3 BP 686 EP 691 DI 10.1007/s00464-014-3722-4 PG 6 WC Surgery SC Surgery GA CB0DU UT WOS:000349296400026 PM 25060682 ER PT J AU Maria, MMMS Hartwell, KJ Hanlon, CA Canterberry, M Lematty, T Owens, M Brady, KT George, MS AF Maria, Megan M. Moran-Santa Hartwell, Karen J. Hanlon, Colleen A. Canterberry, Melanie Lematty, Todd Owens, Max Brady, Kathleen T. George, Mark S. TI Right anterior insula connectivity is important for cue-induced craving in nicotine-dependent smokers SO ADDICTION BIOLOGY LA English DT Article DE Craving; cues; functional connectivity; insula; nicotine-dependence; tobacco cigarettes ID SUSTAINED-RELEASE BUPROPION; FUNCTIONAL CONNECTIVITY; DEFAULT-MODE; TOBACCO WITHDRAWAL; SMOKING-CESSATION; CIGARETTE-SMOKING; CONTROLLED-TRIAL; RESTING BRAIN; NETWORKS; ADDICTION AB The insula has been implicated in cue-induced craving and relapse in nicotine-dependent tobacco cigarette smokers. The aims of the present study were to identify brain regions that exhibit greater functional connectivity with the right anterior insula in response to smoking cues than to neutral cues and the role of functional connectivity between these regions in mediating cue-induced craving in healthy (free of axis I psychiatric disorders) nicotine-dependent tobacco cigarette smokers. Functional magnetic resonance imaging data were collected from 63 healthy nicotine-dependent smokers viewing blocks of smoking and neutral cues. Craving ratings were obtained after each block. A psychophysiologic interaction approach was used to identify regions that exhibited significantly greater functional connectivity with the right anterior insula (seed) during the smoking cues than during the neutral (corrected cluster thresholding, Z>2.3, P=0.05). Parameter estimates of the interaction effects from each region were regressed against the mean cue-induced craving scores. Significant task by seed interactions were observed in two clusters centered in the bilateral precuneus and left angular gyrus. The strength of connectivity between the right anterior insula and the precuneus, which is involved interoceptive processing and self-awareness, was positively correlated with the magnitude of the craving response to the smoking cues (r(2)=0.15; P<0.01). These data suggest that among smokers, cue-induced craving may be a function of connectivity between two regions involved in interoception and self-awareness. Moreover, treatment strategies that incorporate mindful attention may be effective in attenuating cue-induced craving and relapse in nicotine-dependent smokers. C1 [Maria, Megan M. Moran-Santa; Hartwell, Karen J.; Hanlon, Colleen A.; Canterberry, Melanie; Lematty, Todd; Owens, Max; Brady, Kathleen T.; George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC 29425 USA. [Hartwell, Karen J.; Brady, Kathleen T.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Maria, MMMS (reprint author), Med Univ S Carolina, Inst Psychiat, Clin Neurosci Div, 67 President St, Charleston, SC 29425 USA. EM moranm@musc.edu NR 46 TC 7 Z9 7 U1 6 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD MAR PY 2015 VL 20 IS 2 BP 407 EP 414 DI 10.1111/adb.12124 PG 8 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA CB0HG UT WOS:000349305900020 ER PT J AU Stein, CH Faigin, DA AF Stein, Catherine H. Faigin, David A. TI Community-Based Arts Initiatives: Exploring the Science of the Arts SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article DE Community-based arts; Arts-based research; Social action AB In this introduction to the special issue, we describe some of the rewards and challenges of community-based arts initiatives for our discipline. We explore the inherent tensions between art and science that are reflected in community-based arts activities. We pose larger questions about researching community-based arts activities and defining the arts as a means of promoting social change. The diversity of populations, settings, and issues represented by the papers in the special issue are described and a common set of values, methods of inquiry and action are discussed. C1 [Stein, Catherine H.] Bowling Green State Univ, Dept Psychol, Bowling Green, OH 43404 USA. [Faigin, David A.] VA Maine Hlth Care Syst, US Dept Vet Affairs, Lewiston, ME USA. RP Stein, CH (reprint author), Bowling Green State Univ, Dept Psychol, Bowling Green, OH 43404 USA. EM cstein@bgsu.edu NR 13 TC 1 Z9 1 U1 1 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0562 EI 1573-2770 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD MAR PY 2015 VL 55 IS 1-2 BP 70 EP 73 DI 10.1007/s10464-014-9698-3 PG 4 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA CA6KW UT WOS:000349023400007 PM 25586502 ER PT J AU Faigin, DA Stein, CH AF Faigin, David A. Stein, Catherine H. TI Community-Based Theater and Adults with Psychiatric Disabilities: Social Activism, Performance and Community Engagement SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article DE Theater; Community-based theater; Psychiatric disabilities; Mental health activism; Qualitative research; Grounded theory ID MENTAL-HEALTH NEEDS; DRAMA THERAPY; RECOVERY; SELF; PEOPLE; CONSUMER; ILLNESS; SCHIZOPHRENIA; EMPOWERMENT; PROVIDERS AB The present study is an in-depth qualitative inquiry with an established theater troupe composed of adults living with psychiatric disabilities known as The Stars of Light. A grounded theory methodology is used to describe dimensions of social activism and characteristics of theater as a medium of engagement at the individual, setting/troupe, and community levels of analysis. Analysis of a broad scope of interview data, performance content, community contacts, and historical data from the troupe's 19-year history led to the identification of eight emergent theoretical concepts formulated from 17 supporting associated themes. The theoretical concepts characterize the impacts of community-based theater in the lives of participants, and theater troupe processes that contribute to community education and positive social change for adults living with psychiatric disabilities. Advantages, limitations, and future directions for research and action in community-based theater settings are discussed within the context of present research findings. C1 [Faigin, David A.] US Dept Vet Affairs, VA Maine Heath Care Syst, Lewiston, ME 04240 USA. [Stein, Catherine H.] Bowling Green State Univ, Dept Psychol, Bowling Green, OH 43403 USA. RP Faigin, DA (reprint author), US Dept Vet Affairs, VA Maine Heath Care Syst, Lewiston, ME 04240 USA. EM dfaigin@gmail.com NR 58 TC 0 Z9 0 U1 3 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0091-0562 EI 1573-2770 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD MAR PY 2015 VL 55 IS 1-2 BP 148 EP 163 DI 10.1007/s10464-014-9695-6 PG 16 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA CA6KW UT WOS:000349023400014 PM 25520209 ER PT J AU Gelernter, J Kranzler, HR Sherva, R Almasy, L Herman, AI Koesterer, R Zhao, HY Farrer, LA AF Gelernter, Joel Kranzler, Henry R. Sherva, Richard Almasy, Laura Herman, Aryeh I. Koesterer, Ryan Zhao, Hongyu Farrer, Lindsay A. TI Genome-Wide Association Study of Nicotine Dependence in American Populations: Identification of Novel Risk Loci in Both African-Americans and European-Americans SO BIOLOGICAL PSYCHIATRY LA English DT Article DE AMPK pathway; DISC1; DLC1; eNOS pathway; FTND; GWAS; Nicotine dependence; Population differences ID REGULAR TOBACCO USE; SMOKING INITIATION; ALCOHOL DEPENDENCE; TWIN; METAANALYSES; DISORDER; BEHAVIOR; CALCIUM; GENES AB BACKGROUND: We report a genome-wide association study (GWAS) of nicotine dependence defined on the basis of scores on the Fagerstrom Test for Nicotine Dependence in European-American (EA) and African-American (AA) populations. METHODS: Our sample, from the one used in our previous GWAS, included only subjects who had smoked >100 cigarettes lifetime (2114 EA and 2602 AA subjects) and an additional 927 AA and 2003 EA subjects from the Study of Addiction: Genetics and Environment project [via the database of Genotypes and Phenotypes (dbGAP)]. GWAS analysis considered Fagerstrom Test for Nicotine Dependence score as an ordinal trait, separately in each population and sample and by combining the results in meta-analysis. We also conducted analyses that were adjusted for other substance use disorder criteria in a single nucleotide polymorphism (SNP) subset. RESULTS: In EAs, one chromosome 7 intergenic region was genome-wide significant (GWS): rs13225753, p = 3.48 x 10(-8) (adjusted). In AAs, GWS associations were observed at numerous SNPs mapped to a region on chromosome 14 of >305,000 base pairs (minimal p = 4.74 x 10(-10)). Two chromosome 8 regions were associated: p = 4.45 x 10(-8) at DLC1 SNP rs289519 (unadjusted) and p = 1.10 x 10(-9) at rs6996964 (adjusted for other substances), located between CSGALNACT1 and INTS10. No GWS associations were observed at the chromosome 15 nicotinic receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) previously associated with nicotine dependence and smoking quantity traits. TSNAX-DISC1 SNP rs821722 (p = 1.46 x 10(-7)) was the most significant result with substantial contributions from both populations; we previously identified DISC1 associations with opioid dependence. Pathway analysis identified association with nitric oxide synthase and adenosine monophosphate-activated protein kinase pathways in EAs. CONCLUSIONS: The key risk loci identified, which require replication, offer novel insights into nicotine dependence biology. C1 [Gelernter, Joel; Herman, Aryeh I.] Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, New Haven, CT USA. [Gelernter, Joel; Herman, Aryeh I.] Vet Affairs Connecticut Healthcare Ctr, Dept Genet, West Haven, CT USA. [Gelernter, Joel; Herman, Aryeh I.] Vet Affairs Connecticut Healthcare Ctr, Dept Neurobiol, West Haven, CT USA. [Kranzler, Henry R.] Univ Penn, Perelman Sch Med, Dept Psychiat, Ctr Studies Addict, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia Vet Affairs Med Ctr, Vet Integrated Serv Network, Mental Illness Res Educ and Clin Ctr 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 Genet, San Antonio, TX USA. [Zhao, Hongyu] Yale Univ, Dept Biostat, Sch Publ Hlth, New Haven, CT USA. [Zhao, Hongyu] Yale Univ, Dept Genet, Sch Publ Hlth, New Haven, CT USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol & Biostat, Boston, MA 02118 USA. [Farrer, Lindsay A.] Sch Publ Hlth, Boston, MA 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]; Veterans Affairs Connecticut and Philadelphia Veterans Affairs Mental Illness Research, Educational, and Clinical Centers FX This study was supported by National Institutes of Health Grants RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, and R01 AA017535 and the Veterans Affairs Connecticut and Philadelphia Veterans Affairs Mental Illness Research, Educational, and Clinical Centers. NR 39 TC 18 Z9 19 U1 4 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2015 VL 77 IS 5 BP 493 EP 503 DI 10.1016/j.biopsych.2014.08.025 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CA8XH UT WOS:000349203800012 PM 25555482 ER PT J AU Carvalho, S Boggio, PS Goncalves, OF Vigario, AR Faria, M Silva, S do Rego, GG Fregni, F Leite, J AF Carvalho, Sandra Boggio, Paulo S. Goncalves, Oscar F. Vigario, Ana Rita Faria, Marisa Silva, Soraia do Rego, Gabriel Gaudencio Fregni, Felipe Leite, Jorge TI Transcranial Direct Current Stimulation Based Metaplasticity Protocols in Working Memory SO BRAIN STIMULATION LA English DT Article DE Working memory; N-Back; Metaplasticity; Pre-conditioning and conditioning tDCS; DLPFC ID HUMAN MOTOR CORTEX; DORSOLATERAL PREFRONTAL CORTEX; NONINVASIVE BRAIN-STIMULATION; HOMEOSTATIC PLASTICITY; MAGNETIC STIMULATION; EXCITABILITY; INDUCTION; TDCS AB Background: It has been already shown that delivering tDCS that are spaced by an interval alters its impact on motor plasticity. These effects can be explained, based on metaplasticity in which a previous modification of activity in a neuronal network can change the effects of subsequent interventions in the same network. But to date there is limited data assessing metaplasticity effects in cognitive functioning. Objectives: The aim of this study was to test several tDCS-based metaplasticity protocols in working memory (WM), by studying the impact of various interstimulation intervals in the performance of a 3-back task. Methods: Fifteen healthy volunteers per experiment participated in this study. Experiments 1 and 2 tested an anodal tDCS-induced metaplasticity protocol (1 mA, 10 + 10') with 3 interstimulation intervals (10, 30, and 60 min). Experiment 3 determined the effects of a similar protocold with a 10-min interval between two sessions of cathodal tDCS or anodal plus cathodal tDCS (1 mA, 10 + 10'). Results: Two consecutive sessions of anodal tDCS delivered with a 10 min interval between them did not improve WM performance (P = .095). This effect remained the same if the interval was increased to 30 or 60 min. In contrast, when a 10 min interval was given between two consecutive cathodal tDCS sessions, performance in the 3 back task increased (P = .042). Conclusions: These results suggest that the polarity effects of tDCS on working memory are dependent on the previous level of activity of the recruited neural population. (C) 2015 Elsevier Inc. All rights reserved. C1 [Carvalho, Sandra; Goncalves, Oscar F.; Vigario, Ana Rita; Faria, Marisa; Silva, Soraia; Leite, Jorge] Univ Minho, CIPsi Sch Psychol EPsi, Neuropsychophysiol Lab, P-4710057 Braga, Portugal. [Carvalho, Sandra; Goncalves, Oscar F.; Fregni, Felipe; Leite, Jorge] Harvard Univ, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Spaulding Neuromodulat Ctr,Sch Med, Boston, MA USA. [Carvalho, Sandra; Goncalves, Oscar F.; Fregni, Felipe; Leite, Jorge] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Boggio, Paulo S.; do Rego, Gabriel Gaudencio] Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Social & Cognit Neurosci Lab, BR-01241001 Sao Paulo, Brazil. [Boggio, Paulo S.; do Rego, Gabriel Gaudencio] Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Dev Disorders Program, BR-01241001 Sao Paulo, Brazil. [Goncalves, Oscar F.] Northeastern Univ, Bouve Coll Hlth Sci, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. RP Carvalho, S (reprint author), Univ Minho, CIPsi Sch Psychol EPsi, Neuropsychophysiol Lab, Campus Gualtar, P-4710057 Braga, Portugal. EM sandrarc@psi.uminho.pt RI Boggio, Paulo/K-6272-2012; Goncalves, Oscar/G-5278-2010; Leite, Jorge/E-4404-2013; OI Boggio, Paulo/0000-0002-6109-0447; Goncalves, Oscar/0000-0003-2735-9155; Leite, Jorge/0000-0002-0323-9012; Carvalho, Sandra/0000-0003-1759-5146 FU Portuguese Foundation for Science and Technology (FCT) [SFRH/BPD/86041/2012, SFRH/BPD/86027/2012] FX This work was supported by the Portuguese Foundation for Science and Technology (FCT) with two individual grants (SFRH/BPD/86041/2012 and SFRH/BPD/86027/2012). NR 26 TC 2 Z9 3 U1 0 U2 11 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 MAR-APR PY 2015 VL 8 IS 2 BP 289 EP 294 DI 10.1016/j.brs.2014.11.011 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CA4EK UT WOS:000348856800017 PM 25550147 ER PT J AU Del Carmen, MG AF Del Carmen, Marcela G. TI Adnexal Masses SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 [Del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Vincent Dept Obstet & Gynecol, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, Boston, MA USA. RP Del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Dept Obstet & Gynecol, Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2015 VL 58 IS 1 BP 1 EP 2 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CA0GC UT WOS:000348594000001 PM 25551697 ER PT J AU Bennett, JA Oliva, E AF Bennett, Jennifer A. Oliva, Esther TI Pathology of the Adnexal Mass SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE adnexal mass; premenopausal; postmenopausal; differential diagnosis ID CLEAR-CELL CARCINOMA; CORD-STROMAL TUMORS; ENDOCERVICAL ADENOCARCINOMAS; ENDOMETRIOID TUMORS; OVARIAN CARCINOMAS; METASTATIC TUMORS; NEOPLASMS; IDENTIFICATION; EXPRESSION; KRUKENBERG AB An "adnexal mass'' is a common specimen encountered in the daily pathology practice. Although most are benign, the incidence of malignancy increases with age, and approximately 30% are malignant in postmenopausal females. Herein we describe the salient macroscopic and microscopic features of the most prevalent adnexal masses. The entities are separated based on patients' age into premenopausal and postmenopausal, with further subdivision into non-neoplastic lesions, benign and malignant neoplasms, and those of uncertain behavior. For each entity, a brief differential diagnosis is discussed and for the malignant neoplasms, tables highlighting the key immunohistochemical differences that may be helpful are provided. C1 [Bennett, Jennifer A.; Oliva, Esther] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Bennett, Jennifer A.; Oliva, Esther] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Warren 251 A,55 Fruit St, Boston, MA 02114 USA. EM eoliva@partners.org NR 22 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 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2015 VL 58 IS 1 BP 3 EP 27 PG 25 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CA0GC UT WOS:000348594000002 PM 25608250 ER PT J AU Hall, TR Randall, TC AF Hall, Tracilyn R. Randall, Thomas C. TI Adnexal Masses in the Premenopausal Patient SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE premenopausal; adnexal mass; cyst aspiration ID ADVANCED OVARIAN-CANCER; TRANSVAGINAL ULTRASONOGRAPHY; EXPECTANT MANAGEMENT; PELVIC EXAMINATION; TUMOR-MARKERS; GUIDELINES; PREGNANCY; SURVIVAL; SURGERY; WOMEN AB Practitioners may frequently encounter adnexal masses in premenopausal women. Adnexal masses can represent a wide variety of etiologies, and therefore they can represent a diagnostic dilemma. When an adnexal mass is found the initial work up must focus on identifying acute pathology followed by determining the risk of a malignancy. Pelvic ultrasound remains the mainstay for evaluation of adnexal masses in premenopausal patients. If ultrasounds findings are indeterminate magnetic resonance imaging (MRI) is the next imaging modality of choice. The evaluation for malignancy should include serum marker screening. Aspiration of adnexal masses is generally avoided, due to the lack of therapeutic benefit and risk of seeding a tumor. When ultrasound findings are suggestive of benign disease, conservative management, including repeat imaging, should be considered. If the clinical suspicion for malignancy is high referral to a gynecologic oncologist is warranted. In other patients whom the evaluation of their adnexal mass remains unclear surgical excision with care not to disrupt the integrity of the mass should be performed for pathologic diagnosis. C1 [Hall, Tracilyn R.; Randall, Thomas C.] Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Hall, Tracilyn R.; Randall, Thomas C.] Harvard Univ, Sch Med, Boston, MA USA. RP Hall, TR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Div Gynecol Oncol, Boston, MA 02114 USA. EM trhall@mgh.harvard.edu NR 45 TC 1 Z9 1 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2015 VL 58 IS 1 BP 47 EP 52 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CA0GC UT WOS:000348594000004 PM 25608252 ER PT J AU Rauh-Hain, JA Melamed, A Buskwofie, A Schorge, JO AF Rauh-Hain, Jose A. Melamed, Alexander Buskwofie, Ama Schorge, John O. TI Adnexal Mass in the Postmenopausal Patient SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE adnexal mass; postmenopausal; ovarian cancer ID POSITRON-EMISSION-TOMOGRAPHY; OVARIAN-CANCER; PELVIC MASSES; TRANSVAGINAL ULTRASONOGRAPHY; COMPUTED-TOMOGRAPHY; WOMEN; DIAGNOSIS; TUMORS; GUIDELINES; MRI AB The adnexal mass in a postmenopausal patient poses an important diagnostic and management dilemma for primary care providers and gynecologists. Postmenopausal women are at a significantly increased risk of gynecologic malignancy; yet even in this population the majority of adnexal masses are benign. Evaluation and management of these lesions centers on the identification of malignancy, especially ovarian cancer, while avoiding unnecessary intervention in patients with benign lesions. Tumor markers and imaging can help in the evaluation of adnexal mass in postmenopausal women. Transvaginal ultrasound has long been considered the imaging modality of choice for the evaluation of adnexal masses. Particularly in the setting of high frequency utilization of transvaginal probes, which project high quality images allowing for detailed descriptions of the macroscopic appearance of the mass, and remains the least expensive of all imaging modalities currently available. For adnexal masses that are highly suspicious for cancer, women should be referred a gynecologic oncologist and facility for optimal care. C1 [Rauh-Hain, Jose A.; Melamed, Alexander; Buskwofie, Ama; Schorge, John O.] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [Melamed, Alexander; Buskwofie, Ama] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Schorge, JO (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Yawkey 9 E, Boston, MA 02114 USA. EM jschorge@partners.org OI Melamed, Alexander/0000-0002-0654-0863 NR 52 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 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2015 VL 58 IS 1 BP 53 EP 65 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CA0GC UT WOS:000348594000005 PM 25565080 ER PT J AU Sisodia, RMC Del Carmen, MG Boruta, DM AF Sisodia, Rachel M. Clark Del Carmen, Marcela G. Boruta, David M. TI Role of Minimally Invasive Surgery in the Management of Adnexal Masses SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE laparoscopy; adnexal masses; ovarian neoplasm ID OVARIAN-CANCER; PREGNANCY; LAPAROSCOPY; DIAGNOSIS; SURVIVAL; BENIGN; OBESE; CARE AB Adnexal masses are common in women of all ages, and up to 10% of these women will undergo surgical removal of an ovarian mass. Laparoscopy is increasingly being viewed as the preferred surgical approach for management of these masses. Contra-indications to laparoscopy are few, and multiple studies have shown benefits over laparotomy with respect to length of hospital stay, complications, and pain. Minimally invasive surgery can safely be performed by appropriately trained surgeons in almost all patient populations, including pregnancy and the morbidly obese. C1 [Sisodia, Rachel M. Clark; Del Carmen, Marcela G.; Boruta, David M.] Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Sisodia, Rachel M. Clark; Del Carmen, Marcela G.; Boruta, David M.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Sisodia, RMC (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. EM rmclark@partners.org NR 25 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 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2015 VL 58 IS 1 BP 66 EP 75 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CA0GC UT WOS:000348594000006 PM 25608253 ER PT J AU Kelleher, CM Goldstein, AM AF Kelleher, Cassandra M. Goldstein, Allan M. TI Adnexal Masses in Children and Adolescents SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE ovarian cyst; ovarian mass; adolescent; child; adnexal mass; adnexal torsion; ovarian cancer ID OF-THE-LITERATURE; MALIGNANT GERM-CELL; EPITHELIAL OVARIAN-TUMORS; CLINICOPATHOLOGICAL ANALYSIS; CONSERVATIVE MANAGEMENT; RETROSPECTIVE ANALYSIS; GONADAL-DYSGENESIS; SINGLE-INSTITUTION; STROMAL TUMORS; CASE SERIES AB Adnexal masses in children encompass a variety of lesions of the ovaries and fallopian tubes, including ovarian cysts and tumors (benign or malignant), fallopian tube cysts and abscesses, paratubal cysts, and endometriomas. When developing a differential diagnosis for adnexal masses in childhood, the clinician must have a broad understanding of adnexal pathology and consider the patient's age, presenting complaints, physical examination findings, and imaging results to generate a list of possible diagnoses and the appropriate treatment plan. We review the clinical presentation of these lesions and discuss the current recommendations for their management. C1 [Kelleher, Cassandra M.; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. RP Kelleher, CM (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. EM ckelleher3@partners.org NR 93 TC 2 Z9 2 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2015 VL 58 IS 1 BP 76 EP 92 PG 17 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CA0GC UT WOS:000348594000007 PM 25551698 ER PT J AU Naqvi, M Kaimal, A AF Naqvi, Mariam Kaimal, Anjali TI Adnexal Masses in Pregnancy SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE adnexal mass; adnexal cyst; ovarian cyst; pregnancy; ovarian torsion ID LAPAROSCOPIC SURGERY; CESAREAN-SECTION; OVARIAN MASSES; MANAGEMENT; ULTRASOUND; DIAGNOSIS; SONOGRAPHY; PREVALENCE; LAPAROTOMY; TORSION AB With the advent of routine obstetrical ultrasound, the diagnosis of an adnexal mass in pregnancy has become increasingly common. Although the reported incidence and expected clinical course varies based on the gestational age at the time of diagnosis and the criteria used to define an adnexal mass, the majority of adnexal masses diagnosed in pregnancy are benign and are likely to resolve without complication or intervention. This review will discuss the epidemiology of adnexal masses in pregnancy, diagnostic tools, potential complications, and management options during pregnancy. C1 [Naqvi, Mariam; Kaimal, Anjali] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Kaimal, A (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Founders 460, Boston, MA 02114 USA. EM akaimal@partners.org NR 38 TC 2 Z9 2 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2015 VL 58 IS 1 BP 93 EP 101 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CA0GC UT WOS:000348594000008 PM 25551696 ER PT J AU Ackman, JB Verzosa, S Kovach, AE Louissaint, A Lanuti, M Wright, CD Shepard, JAO Halpern, EF AF Ackman, Jeanne B. Verzosa, Stacey Kovach, Alexandra E. Louissaint, Abner, Jr. Lanuti, Michael Wright, Cameron D. Shepard, Jo-Anne O. Halpern, Elkan F. TI High rate of unnecessary thymectomy and its cause. Can computed tomography distinguish thymoma, lymphoma, thymic hyperplasia, and thymic cysts? SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Nontherapeutic thymectomy rate; Thymic cyst; Thymic hyperplasia; Lymphoma; Thymoma; CT misinterpretation ID NONTHYMOMATOUS MYASTHENIA-GRAVIS; CELL LUNG-CANCER; CT APPEARANCE; FEATURES; MASSES; TUMORS; MRI AB Purpose: To determine the non-therapeutic thymectomy rate in a recent six-year consecutive thymectomy cohort, the etiology of these unnecessary thymectomies, and the differentiating CT features of thymoma, lymphoma, thymic hyperplasia, and thymic cysts. Materials and methods: Electronic data base query of all thymectomies performed at the Massachusetts General Hospital from 2006 to 2012 yielded 160 thymectomy cases, 124 of which had available imaging. The non-therapeutic thymectomy rate (includes thymectomy for lymphoma and benign disease) was calculated. Preoperative clinical and CT imaging features were assessed by review of the in-house electronic medical record by 2 thoracic surgeons and 2 pathology-blinded radiologists, respectively. Results: The non-therapeutic thymectomy rate of 43.8% (70/160) was largely secondary to concern for thymoma and was comprised of lymphoma (54.3%, 38/70), thymic bed cysts (24.3%, 17/70), thymic hyperplasia (17.1%, 12/70), and reactive or atrophic tissue (4.3%, 3/70). Among these four lesions, there were significant differences in location with respect to midline, morphology, circumscription, homogeneity of attenuation, fatty intercalation, coexistent lymphadenopathy, overt pericardial invasion, and mass effect( p < 0.001). True thymic cysts ranged in attenuation from -20 to 58 Hounsfield units (HU), with a mean attenuation of 23 HU. Conclusion: The high rate of unnecessary thymectomy was due to misinterpretation of thymic cysts, thymic hyperplasia, and lymphoma as thymoma on chest CT. This study demonstrates differentiating features between thymoma, lymphoma, thymic hyperplasia, and thymic cysts on chest CT which may help triage more patients away from thymectomy toward less invasive and non-invasive means of diagnosis and thereby lower the non-therapeutic thymectomy rate. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Ackman, Jeanne B.] Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Ackman, JB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging & Intervent, Founders House 202,55 Fruit St, Boston, MA 02114 USA. EM jackman@mgh.harvard.edu; sverzosa@mgh.harvard.edu; akovach@mgh.harvard.edu; alouissaint@mgh.harvard.edu; mlanuti@mgh.harvard.edu; cdwright@mgh.harvard.edu; jshepard@mgh.harvard.edu; elk@mgh-ita.org NR 37 TC 11 Z9 11 U1 1 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2015 VL 84 IS 3 BP 524 EP 533 DI 10.1016/j.ejrad.2014.11.042 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CA8NN UT WOS:000349177800028 PM 25575742 ER PT J AU Martin, NE Massey, L Stowell, C Bangma, C Briganti, A Bill-Axelson, A Blute, M Catto, J Chen, RC D'Amico, AV Feick, G Fitzpatrick, JM Frank, SJ Froehner, M Frydenberg, M Glaser, A Graefen, M Hamstra, D Kibel, A Mendenhall, N Moretti, K Ramon, J Roos, I Sandler, H Sullivan, FJ Swanson, D Tewari, A Vickers, A Wiegel, T Huland, H AF Martin, Neil E. Massey, Laura Stowell, Caleb Bangma, Chris Briganti, Alberto Bill-Axelson, Anna Blute, Michael Catto, James Chen, Ronald C. D'Amico, Anthony V. Feick, Guenter Fitzpatrick, John M. Frank, Steven J. Froehner, Michael Frydenberg, Mark Glaser, Adam Graefen, Markus Hamstra, Daniel Kibel, Adam Mendenhall, Nancy Moretti, Kim Ramon, Jacob Roos, Ian Sandler, Howard Sullivan, Francis J. Swanson, David Tewari, Ashutosh Vickers, Andrew Wiegel, Thomas Huland, Hartwig TI Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer SO EUROPEAN UROLOGY LA English DT Article DE Outcome measurement; Patient-reported ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; FUNCTIONAL OUTCOMES; REPORTED OUTCOMES; VALIDATION; SURVIVORS; QUESTIONNAIRE; BRACHYTHERAPY; COMORBIDITY; MORBIDITY AB Background: Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment. Objective: To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value. Design, setting, and participants: We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices. Outcome measurements and statistical analysis: The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set. Results and limitations: We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons. Conclusions: We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care. Patient summary: Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer. (C) 2014 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license C1 [Martin, Neil E.; Massey, Laura; Stowell, Caleb] Int Consortium Hlth Outcomes Measurement, Cambridge, MA USA. [Martin, Neil E.; D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Bangma, Chris] Erasmus MC, Dept Urol, Rotterdam, Netherlands. [Briganti, Alberto] Vita Salute San Raffaele Univ Hosp, Dept Urol, Prostate Canc Res Programme, Urol Res Inst, Milan, Italy. [Bill-Axelson, Anna] Univ Uppsala Hosp, Dept Surg Sci, Dept Urol, Uppsala, Sweden. [Bill-Axelson, Anna] Natl Prostate Canc Register Sweden, Uppsala, Sweden. [Blute, Michael] Harvard Univ, Dept Urol, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Catto, James] Univ Sheffield, Acad Urol Unit, Sheffield, S Yorkshire, England. [Catto, James] Univ Sheffield, Sch Med, Sheffield Canc Res Ctr, Acad Unit Mol Oncol,CR UK YCR, Sheffield, S Yorkshire, England. [Chen, Ronald C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Feick, Guenter] Bundesverband Prostatakrebs Selbsthilfe, Pohlheim, Germany. [Fitzpatrick, John M.] Irish Canc Soc, Dublin, Ireland. [Frank, Steven J.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Froehner, Michael] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Urol, D-01062 Dresden, Germany. [Frydenberg, Mark] Monash Univ, Dept Surg, Clayton, Vic 3800, Australia. [Glaser, Adam] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. [Graefen, Markus; Huland, Hartwig] Univ Med Ctr Hamburg Eppendorf, Martini Klin, Hamburg, Germany. [Hamstra, Daniel] Univ Michigan Hlth Syst, Dept Radiat Oncol, Ann Arbor, MI USA. [Kibel, Adam] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Mendenhall, Nancy] Univ Florida, Proton Therapy Inst, Jacksonville, FL USA. [Moretti, Kim] Repatriat Gen Hosp, South Australian Prostate Canc Clin Outcomes Coll, Daw Pk, SA, Australia. [Ramon, Jacob] Chaim Sheba Med Ctr, Dept Urol & Urooncol, IL-52621 Tel Hashomer, Israel. [Roos, Ian] Canc Voices Australia, Melbourne, Vic, Australia. [Sandler, Howard] Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA. [Sullivan, Francis J.] NUI Galway, Prostate Canc Inst, Galway, Ireland. [Swanson, David] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Tewari, Ashutosh] Mt Sinai Hosp, Icahn Sch Med, Dept Urol, New York, NY 10029 USA. [Vickers, Andrew] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Wiegel, Thomas] Univ Hosp Ulm, Dept Radiat Oncol, Ulm, Germany. RP Martin, NE (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM nmartin@lroc.harvard.edu RI Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Vickers, Andrew/0000-0003-1525-6503; catto, james/0000-0003-2787-8828 FU Movember Foundation FX Movember Foundation helped design and conduct the study and collect the data. NR 26 TC 37 Z9 37 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD MAR PY 2015 VL 67 IS 3 BP 460 EP 467 DI 10.1016/j.eururo.2014.08.075 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CB1GD UT WOS:000349374200021 PM 25234359 ER PT J AU Nierenberg, AA Ostergaard, SD Iovieno, N Walker, RSW Fava, M Papakostas, GI AF Nierenberg, Andrew A. Ostergaard, Soren D. Iovieno, Nadia Walker, Rosemary S. W. Fava, Maurizio Papakostas, George I. TI Predictors of placebo response in bipolar depression SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE bipolar depression; clinical trials; placebo response ID PSYCHIATRY WFSBP GUIDELINES; RANDOMIZED CLINICAL-TRIALS; DOUBLE-BLIND; I DEPRESSION; TREATMENTS METAANALYSIS; BIOLOGICAL TREATMENT; DIAGNOSTIC CRITERIA; WORLD FEDERATION; META-REGRESSION; ACUTE MANIA AB The aim of this work is to investigate placebo response rates in placebo-controlled randomized clinical trials (RCTs) of pharmacological therapy in bipolar depression (BPD) and to identify predictors of placebo response and clinical trial outcome in BPD. Medline/PubMed publication databases were searched for RCTs of oral drugs used as monotherapy for the treatment of BPD, published between January 1980 and September 2013. Data extracted from 12 manuscripts and one poster, representing a total of 17 clinical trials, were pooled. Pooled response rates for drug and placebo were 55.1 and 39.2%, corresponding to a risk ratio for responding to active treatment versus placebo of 1.29 (P<0.001). The probability of receiving placebo and trial duration correlated with the response rate to placebo. A meta-regression showed that trial duration and baseline severity correlated with the risk ratio of responding to drug versus placebo. There was a trend toward statistical significance for a greater probability of receiving placebo to predict greater drug-placebo 'separation'. In conclusion, several modifiable factors, specifically the probability of receiving placebo, baseline illness severity, and trial duration, correlate with placebo response rates and/or clinical trial outcome in RCTs of pharmacotherapy for BPD, and should be taken into account when designing studies for BPD. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Nierenberg, Andrew A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.; Iovieno, Nadia; Walker, Rosemary S. W.; Fava, Maurizio; Papakostas, George I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. [Iovieno, Nadia; Fava, Maurizio; Papakostas, George I.] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA. [Ostergaard, Soren D.] Aarhus Univ Hosp Risskov, Res Unit, Dept P, Risskov, Denmark. [Ostergaard, Soren D.] Lundbeck Fdn, Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark. RP Nierenberg, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin, 50 Staniford St, Boston, MA 02114 USA. EM anierenberg@partners.org OI Ostergaard, Soren Dinesen/0000-0002-8032-6208 FU AstraZeneca PLC; Bristol-Myers Squibb Company; Forest Pharmaceuticals; National Institute of Mental Health; PAMLAB LLC; Pfizer Inc.; Ridge Diagnostics; Sunovion Pharmaceuticals; Theracos Inc.; Abbot Laboratories; Alkermes Inc.; American Cyanamid; Aspect Medical Systems; AstraZeneca; BioResearch; Brain Cells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals Inc.; Euthymics Bioscience Inc.; Forest Pharmaceuticals Inc.; Ganeden Biotech Inc.; GlaxoSmithKline; Harvard Clinical Research Institute; Hoffman-LaRoche; Icon Clinical Research; i3 Innovus/Ingenix; Janssen RD, LLC; Jed Foundation; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; MedAvante; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Neuralstem Inc.; Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pharmacia-Upjohn; Pharmaceutical Research Associates Inc.; Pharmavite LLC; PharmoRx Therapeutics; Photothera; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals Inc.; Synthelabo; Wyeth-Ayerst Laboratories; AHRQ; Elan; Forest; Mylan; NIMH; PamLabs; Pfizer Pharmaceuticals; Takeda FX Dr Papakostas has served as a consultant for Abbott Laboratories, AstraZeneca PLC, Avanir Pharmaceuticals, Brainsway Ltd, Bristol-Myers Squibb Company, Cephalon Inc., Dey Pharma, L.P., Eli Lilly Co., GlaxoSmithKline, Evotec AG, H. Lundbeck A/S, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Novartis Pharma AG, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer Inc., Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceutical Company Ltd, Theracos Inc., and Wyeth Inc. Dr Papakostas has received honoraria from Abbott Laboratories, AstraZeneca PLC, Avanir Pharmaceuticals, Bristol-Myers Squibb Company, Brainsway Ltd, Cephalon Inc., Dey Pharma, L.P., Eli Lilly Co., Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, H. Lundbeck A/S, Novartis Pharma AG, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceutical Company Ltd, Theracos Inc., Titan Pharmaceuticals, and Wyeth Inc. Dr Papakostas has received research support from AstraZeneca PLC, Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB LLC, Pfizer Inc., Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sunovion Pharmaceuticals, and Theracos Inc. Dr Papakostas has served (not currently) on the speaker's bureau for BristolMyersSquibb Co. and Pfizer Inc.; Dr Fava disclosures are the following: Research Support: Abbot Laboratories; Alkermes Inc.; American Cyanamid; Aspect Medical Systems; AstraZeneca; BioResearch; Brain Cells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals Inc.; Euthymics Bioscience Inc.; Forest Pharmaceuticals Inc.; Ganeden Biotech Inc.; GlaxoSmithKline; Harvard Clinical Research Institute; Hoffman-LaRoche; Icon Clinical Research; i3 Innovus/Ingenix; Janssen R&D, LLC; Jed Foundation; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; MedAvante; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Neuralstem Inc.; Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmacia-Upjohn; Pharmaceutical Research Associates Inc.; Pharmavite LLC; PharmoRx Therapeutics; Photothera; Roche Pharmaceuticals; RCT Logic, LLC (formerly Clinical Trials Solutions, LLC); Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals Inc.; Synthelabo; Wyeth-Ayerst Laboratories. Advisory/Consulting: Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes Inc.; Amarin Pharma Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management Inc.; BioMarin Pharmaceuticals Inc.; Biovail Corporation; Brain Cells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon Inc.; Cerecor; CNS Response Inc.; Compellis Pharmaceuticals; Cypress Pharmaceutical Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dinippon Sumitomo Pharma Co. Inc.; Dov Pharmaceuticals Inc.; Edgemont Pharmaceuticals Inc.; Eisai Inc.; Eli Lilly and Company; EnVivo Pharmaceuticals Inc.; ePharmaSolutions; EPIX Pharmaceuticals Inc.; Euthymics Bioscience Inc.; Fabre-Kramer Pharmaceuticals Inc.; Forest Pharmaceuticals Inc.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals Inc.; Johnson & Johnson Pharmaceutical Research & Development, LLC; Knoll Pharmaceuticals Corp.; Labopharm Inc.; Lorex Pharmaceuticals; Lundbeck Inc.; MedAvante Inc.; Merck & Co. Inc.; MSI Methylation Sciences Inc.; Naurex Inc.; Neuralstem Inc.; Neuronetics Inc.; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; Pamlab, LLC.; Pfizer Inc.; PharmaStar; Pharmavite LLC.; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals Inc.; Puretech Ventures; PsychoGenics; Psylin Neurosciences Inc.; RCT Logic, LLC (formerly Clinical Trials Solutions, LLC); Rexahn Pharmaceuticals Inc.; Ridge Diagnostics Inc.; Roche; Sanofi-Aventis US LLC.; Sepracor Inc.; Servier Laboratories; Schering-Plough Corporation; Solvay Pharmaceuticals Inc.; Somaxon Pharmaceuticals Inc.; Somerset Pharmaceuticals Inc.; Sunovion Pharmaceuticals; Supernus Pharmaceuticals Inc.; Synthelabo; Takeda Pharmaceutical Company Limited; Tal Medical Inc.; Tetragenex Pharmaceuticals Inc.; TransForm Pharmaceuticals Inc.; Transcept Pharmaceuticals Inc.; Vanda Pharmaceuticals Inc. Speaking/Publishing: Adamed Co.; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon Inc.; CME Institute/Physicians Postgraduate Press Inc.; Eli Lilly and Company; Forest Pharmaceuticals Inc.; ; GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer Inc.; PharmaStar; United BioSource Corp.; Wyeth-Ayerst Laboratories. Equity Holdings: Compellis; PsyBrain Inc. Royalty/patent, other income: Patent for Sequential Parallel Comparison Design (SPCD), which are licensed by MGH to RCT Logic, LLC; and patent application for a combination of Ketamine plus Scopolamine in MDD. Copyright for the MGH Cognitive & Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), and SAFER; Lippincott, Williams & Wilkins; Wolters Kluwer; World Scientific Publishing Co. Pte. Ltd.; Dr Nierenberg has consulted for the American Psychiatric Association, Appliance Computing Inc. (Mindsite), Basliea, Brain Cells Inc., Brandeis University, Bristol-Myers Squibb, Clintara, Dey Pharmaceuticals, Dainippon Sumitomo (now Sunovion), Eli Lilly and Company, EpiQ, L.P./Mylan Inc., Forest, Novartis, PamLabs, PGx Health, Shire, Schering-Plough, Sunovion, Takeda Pharmaceuticals, Targacept, and Teva; consulted through the MGH Clinical Trials Network and Institute (CTNI) for AstraZeneca, Brain Cells Inc., Dianippon Sumitomo/Sepracor, Johnson and Johnson, Labopharm, Merck, Methylation Science, Novartis, PGx Health, Shire, Schering-Plough, Targacept and Takeda/Lundbeck Pharmaceuticals; received grant/research support from AHRQ, Cephalon, Elan, Forest, Mylan, NIMH, PamLabs, Pfizer Pharmaceuticals, Shire, and Takeda; received honoraria from Belvoir Publishing, University of Texas Southwestern Dallas, Hillside Hospital, American Drug Utilization Review, American Society for Clinical Psychopharmacology, Baystate Medical Center, Columbia University, CRICO, Dartmouth Medical School, IMEDEX, Israel Society for Biological Psychiatry, Johns Hopkins University, MJ Consulting, New York State, Medscape, MBL Publishing, National Association of Continuing Education, Physicians Postgraduate Press, SUNY Buffalo, University of Wisconsin, University of Pisa, University of Michigan, University of Miami, APSARD, ISBD, SciMed, Slack Publishing and Wolters Kluwer Publishing; was currently or formerly on the advisory boards of Appliance Computing Inc., Brain Cells Inc., Eli Lilly and Company, Johnson and Johnson, Takeda/Lundbeck, Targacept, and InfoMedic; owns stock options in Appliance Computing Inc. and Brain Cells Inc; has copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery-Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI); and has a patent extension application for the combination of buspirone, bupropion, and melatonin for the treatment of depression. NR 49 TC 5 Z9 5 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0268-1315 EI 1473-5857 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD MAR PY 2015 VL 30 IS 2 BP 59 EP 66 DI 10.1097/YIC.0000000000000058 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA CA6FJ UT WOS:000349004700001 PM 25438027 ER PT J AU Acharya, D Harper, DG Achtyes, ED Seiner, SJ Mahdasian, JA Nykamp, LJ Adkison, L White, LV McClintock, SM Ujkaj, M Davidoff, DA Forester, BP AF Acharya, Deepa Harper, David G. Achtyes, Eric D. Seiner, Stephen J. Mahdasian, Jack A. Nykamp, Louis J. Adkison, Lesley White, Lori Van der Schuur McClintock, Shawn M. Ujkaj, Manjola Davidoff, Donald A. Forester, Brent P. TI Safety and utility of acute electroconvulsive therapy for agitation and aggression in dementia SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE ECT; electroconvulsive therapy; dementia; agitation; aggression ID ATYPICAL ANTIPSYCHOTIC MEDICATIONS; ALZHEIMERS-DISEASE; BEHAVIORAL SYMPTOMS; ELDERLY-PATIENTS; NURSING-HOME; MAJOR DEPRESSION; CLINICAL-TRIALS; ECT TREATMENT; EFFICACY; DEATH AB ObjectiveAgitation and aggression are among the most frequent and disruptive behavioral complications of dementia that contribute to increased cost of care, hospitalization, caregiver burden, and risk of premature institutionalization. This current study examined the safety and efficacy of electroconvulsive therapy (ECT) as a treatment for behavioral disturbances in dementia. We hypothesized that ECT would result in reduced agitated and aggressive behaviors between baseline and discharge. MethodsTwenty-three participants admitted to McLean Hospital (Belmont, MA, USA) and Pine Rest Christian Mental Health Services (Grand Rapids, MI, USA), with a diagnosis of dementia who were referred for ECT to treat agitation and/or aggression, were enrolled in the study. We administered the Cohen-Mansfield Agitation Inventory-Short Form, Neuropsychiatric Inventory-Nursing Home Version, Cornell Scale for Depression in Dementia, and the Clinical Global Impression Scale at baseline, during, and after the ECT course. ResultsRegression analyses revealed a significant decrease from baseline to discharge on the Cohen-Mansfield Agitation Inventory (F(4,8)=13.3; p=0.006) and Neuropsychiatric Inventory (F(4,31)=14.6; p<0.001). There was no statistically significant change in scores on the Cornell Scale for Depression in Dementia. The Clinical Global Impression scores on average changed from a rating of markedly agitated/aggressive at baseline to borderline agitated/aggressive at discharge. Treatment with ECT was well tolerated by most participants; discontinuation of ECT occurred for two participants because of recurrence of agitation and for three participants because of adverse events. ConclusionsElectroconvulsive therapy may be a safe treatment option to reduce symptoms of agitation and aggression in patients with dementia whose behaviors are refractory to medication management. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Acharya, Deepa; Harper, David G.; Forester, Brent P.] Harvard Univ, McLean Hosp, Sch Med, Geriatr Mood Disorders Res Program, Belmont, MA 02478 USA. [Acharya, Deepa] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Achtyes, Eric D.; Mahdasian, Jack A.; Nykamp, Louis J.; White, Lori Van der Schuur] Michigan State Univ, Pine Rest Christian Mental Hlth Serv, Grand Rapids, MI USA. [Seiner, Stephen J.; Ujkaj, Manjola] Harvard Univ, McLean Hosp, Sch Med, Psychiat Neurotherapeut Program, Belmont, MA USA. [Adkison, Lesley] McLean Hosp, Geriatr Psychiat Unit, Belmont, MA 02178 USA. [McClintock, Shawn M.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Neurocognit Res Lab,Div Brain Stimulat & Neurophy, Durham, NC USA. [McClintock, Shawn M.] UT Southwestern Med Ctr, Dept Psychiat, Dallas, TX USA. [Davidoff, Donald A.] Harvard Univ, McLean Hosp, Sch Med, Dept Neuropsychol, Belmont, MA USA. RP Acharya, D (reprint author), Harvard Univ, McLean Hosp, Sch Med, Geriatr Mood Disorders Res Program, Belmont, MA 02478 USA. EM dacharya@mclean.harvard.edu RI Achtyes, Eric/M-6024-2016 OI Achtyes, Eric/0000-0001-8939-1535 FU Pine Rest Foundation; National Institute of Mental Health [K23 MH087739]; Brain and Behavior Foundation; Rogers Family Foundation [NIMH K23 MHO77287] FX Eric Achtyes, MD: Parts of this work were supported by a grant from the Pine Rest Foundation; Shawn McClintock, PhD, MHCS: Parts of this work were supported by a grant from the National Institute of Mental Health (K23 MH087739, PI: SM McClintock) and Brain and Behavior Foundation. Consultant for Shire Development; Brent P. Forester, MD: Rogers Family Foundation (NIMH K23 MHO77287) NR 42 TC 3 Z9 3 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 30 IS 3 BP 265 EP 273 DI 10.1002/gps.4137 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CA7ER UT WOS:000349081000005 PM 24838521 ER PT J AU Salazar, R Royall, DR Palmer, RF AF Salazar, Ricardo Royall, Donald R. Palmer, Raymond F. TI Neuropsychiatric symptoms in community-dwelling Mexican-Americans: results from the Hispanic Established Population for Epidemiological Study of the Elderly (HEPESE) study SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Neuropsychiatric Inventory (NPI); neuropsychiatric symptoms (NPS); Hispanics; population-based study; Mexican-Americans ID ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; FAMILY CAREGIVERS; DEMENTIA SEVERITY; CACHE COUNTY; PREVALENCE; DEPRESSION; SAMPLE; CARE; PSYCHOPATHOLOGY AB ObjectiveThe Neuropsychiatric Inventory (NPI) is a well-established measure of psychopathology and frequently used in dementia studies. Little is known about its psychometric characteristics at a population level, particularly among Hispanics. We report the frequency of NPI symptoms in a community-dwelling older Mexican-American (MA) population cohort and the degree of symptom-related distress experienced by participant informants. MethodsParticipants were 1079 MA age 80years and over residing in five southwestern states who were administered the NPI as part of wave-7 of the Hispanic Established Population for Epidemiological Study of the Elderly (HEPESE) conducted from 2010 to 2011. ResultsNine hundred twenty-five informants rated NPI domains. Prevalence of neuropsychiatric symptoms (NPS) varied by symptom domain and ranged from agitation/aggression (32%) to euphoria/elation (5%). The overall rate of behavioral disturbances was 62.7%. On the other hand, 37.3% of informants reported no NPS. A significant fraction of the informants reported distress from the mood disorder cluster of the scale. ConclusionsA large percentage (>60%) of community-dwelling older MA have one or more informant-reported NPS. These symptoms have diagnostic, prognostic, and therapeutic implications. Although neuropsychiatric disorders may be the initial clinical manifestation of dementia and often appear before cognitive alterations, the high frequency of these symptoms in the HEPESE cohort may reflect a high prevalence of these disorders among community-dwelling MA. The pattern we observed also suggests relatively advanced stages of dementia. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Salazar, Ricardo; Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat & Behav Med, San Antonio, TX 78229 USA. [Royall, Donald R.; Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Royall, Donald R.] South Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. RP Salazar, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat & Behav Med, San Antonio, TX 78229 USA. EM salazarr1@uthscsa.edu FU NIA NIH HHS [R01 AG010939] NR 45 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 30 IS 3 BP 300 EP 307 DI 10.1002/gps.4141 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CA7ER UT WOS:000349081000009 PM 24838594 ER PT J AU Karlin, BE Trockel, M Spira, AP Taylor, CB Manber, R AF Karlin, Bradley E. Trockel, Mickey Spira, Adam P. Taylor, C. Barr Manber, Rachel TI National evaluation of the effectiveness of cognitive behavioral therapy for insomnia among older versus younger veterans SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE cognitive behavioral therapy; insomnia; older adults; geriatrics; veterans; US Department of Veterans Affairs; dissemination; implementation; evidence-based psychotherapy ID RANDOMIZED CONTROLLED-TRIAL; WORKING ALLIANCE INVENTORY; BECK DEPRESSION INVENTORY; QUALITY-OF-LIFE; PSYCHOMETRIC PROPERTIES; COMPARATIVE METAANALYSIS; PERSISTENT INSOMNIA; SLEEP DISTURBANCE; DISORDERS; HEALTH AB ObjectivesLimited research has examined the effects of cognitive behavioral therapy for insomnia (CBT-I) among older adults (age >65years) receiving treatment in real-world clinical settings and even less has examined effects on outcomes beyond reducing insomnia, such as improved quality of life. The current article examines and compares outcomes of older versus younger (age 18-64years) veterans receiving CBT-I nationally in nonsleep specialty settings. MethodPatient outcomes were assessed using the Insomnia Severity Index, Beck Depression Inventory-II, and the World Health Organization Quality of Life-BREF. Therapeutic alliance was assessed using the Working Alliance InventoryShort Revised. ResultsA total of 536 younger veterans and 121 older veterans received CBT-I; 77% of older and 64% of younger patients completed all sessions or finished early due to symptom relief. Mean insomnia scores declined from 19.5 to 9.7 in the older group and from 20.9 to 11.1 in the younger group. Within-group effect sizes were d=2.3 and 2.2 for older and younger groups, respectively. CBT-I also yielded significant improvements in depression and quality of life for both age groups. High and increasing levels of therapeutic alliance were observed for both age groups. ConclusionsOlder (and younger) patients receiving CBT-I from nonsleep specialists experienced large reductions in insomnia and improvements in depression and quality of life. Effects were similar for both age groups, and the rate of dropout was lower among older adults. The results provide strong support for the effectiveness and acceptability of CBT-I for older adults receiving care in routine treatment settings. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Karlin, Bradley E.] US Dept Vet Affairs, Mental Hlth Serv, Cent Off, Washington, DC 20420 USA. [Karlin, Bradley E.] Educ Dev Ctr Inc, New York, NY 10014 USA. [Karlin, Bradley E.; Spira, Adam P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. [Trockel, Mickey; Taylor, C. Barr; Manber, Rachel] Stanford Univ, Med Ctr, Dept Psychiat, Stanford, CA 94305 USA. [Trockel, Mickey; Taylor, C. Barr; Manber, Rachel] Vet Affairs Palo Alto Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 21, Palo Alto, CA 94304 USA. RP Karlin, BE (reprint author), US Dept Vet Affairs, Mental Hlth Serv, Cent Off, Washington, DC 20420 USA. EM bradkarlin@gmail.com FU Mental Health Services, US Department of Veterans Affairs (VA) Central Office FX This project was supported by Mental Health Services, US Department of Veterans Affairs (VA) Central Office. NR 52 TC 4 Z9 4 U1 3 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD MAR PY 2015 VL 30 IS 3 BP 308 EP 315 DI 10.1002/gps.4143 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CA7ER UT WOS:000349081000010 PM 24890708 ER PT J AU Wada, N Kawano, Y Fujiwara, S Kikukawa, Y Okuno, Y Tasaki, M Ueda, M Ando, Y Yoshinaga, K Ri, M Iida, S Nakashima, T Shiotsu, Y Mitsuya, H Hata, H AF Wada, Naoko Kawano, Yawara Fujiwara, Shiho Kikukawa, Yoshitaka Okuno, Yutaka Tasaki, Masayoshi Ueda, Mitsuharu Ando, Yukio Yoshinaga, Kazuya Ri, Masaki Iida, Shinsuke Nakashima, Takayuki Shiotsu, Yukimasa Mitsuya, Hiroaki Hata, Hiroyuki TI Shikonin, dually functions as a proteasome inhibitor and a necroptosis inducer in multiple myeloma cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE multiple myeloma; apoptosis; necroptosis; heat shock protein; proteasome ID INDUCED APOPTOSIS; DOWN-REGULATION; CANCER CELLS; DEATH; INDUCTION; PATHWAY; LINES; IDENTIFICATION; ACTIVATION; STRESS AB Shikonin (SHK), a natural small agent (MW 288.3), reportedly induces cell death in various tumor cells. We have found that SHK also exerts potent cytocidal effects on human multiple myeloma (MM) cells, but its anticancer mechanism in MM cells remains to be elucidated. SHK at 2.5-5 mu M induced apoptosis in seven MM cell lines, including the bortezomib-resistant cell line KMS11/BTZ. The IC50 value of SHK against KMS11/BTZ was comparable to that of a parental cell line KMS11 (1.1 and 1.56 mu M, respectively). SHK induces accumulation of ubiquitinated proteins and activates XBP-1 in MM cells, suggesting that SHK functions as a proteasome inhibitor, eventually inducing ER stress-associated apoptosis. SHK increases levels of HSP70/72, which protects cells from apoptosis, and exerts greater cytocidal effects in combination with the HSP70/72 inhibitor VER-155008. At higher concentrations (10-20 mu M), SHK induced cell death, which was completely inhibited by a necroptosis inhibitor, necrostatin-1 (Nec-1), while the cytocidal activity was unaffected by Z-VAD-FMK, strongly suggesting that cell death is induced by SHK at high concentrations through necroptosis. The present data show for the first time that SHK induces cell death in MM cells. SHK efficiently induces apoptosis and combination of heat shock protein inhibitor with low dose SHK enhances apoptosis, while high dose SHK induces necroptosis in MM cells. These findings together support the use of SHK as a potential therapeutic agent for MM. C1 [Wada, Naoko; Fujiwara, Shiho; Kikukawa, Yoshitaka; Okuno, Yutaka; Mitsuya, Hiroaki; Hata, Hiroyuki] Kumamoto Univ Hosp, Dept Hematol, Kumamoto, Japan. [Kawano, Yawara] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ri, Masaki; Iida, Shinsuke] Nagoya City Univ, Dept Hematol & Oncol, Grad Sch Med Sci, Nagoya, Aichi, Japan. [Tasaki, Masayoshi; Ueda, Mitsuharu; Ando, Yukio] Kumamoto Univ, Dept Neurol, Grad Sch Med Sci, Kumamoto, Japan. [Tasaki, Masayoshi; Hata, Hiroyuki] Kumamoto Univ, Div Informat Clin Sci, Grad Sch Hlth Sci, Kumamoto, Japan. [Yoshinaga, Kazuya] Kumamoto Univ, Dept Anat, Grad Sch Hlth Sci, Kumamoto, Japan. [Nakashima, Takayuki] Kyowa Hakko Kirin Co Ltd, Res Funct Unit, Tokyo, Japan. [Shiotsu, Yukimasa] Kyowa Hakko Kirin Calif Inc, Translat Oncol, La Jolla, CA USA. RP Hata, H (reprint author), Kumamoto Univ, Div Informat Clin Sci, Fac Med Sci, Kumamoto, Japan. EM hata@kumamoto-u.ac.jp FU Amyloidosis Research Committee from the Ministry of Health, Labour, and Welfare, Japan FX We are grateful to the Institute of Natural Medicine, Toyama University, Japan for providing natural herbal compounds. This study was supported in part by a grant from the Amyloidosis Research Committee from the Ministry of Health, Labour, and Welfare, Japan. We are also grateful to Ms. Y. Otake for technical assistance. We thank Gene Technology Center, Institute of Resource Development and Analysis, Kumamoto University for technical assistances regarding proteasome activity analysis. NR 39 TC 12 Z9 13 U1 4 U2 12 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 EI 1791-2423 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 2015 VL 46 IS 3 BP 963 EP 972 DI 10.3892/ijo.2014.2804 PG 10 WC Oncology SC Oncology GA CA6XW UT WOS:000349061800007 PM 25530098 ER PT J AU Lee, HJ Yoon, C Park, DJ Kim, YJ Schmidt, B Lee, YJ Tap, WD Eisinger-Mathason, TSK Choy, E Kirsch, DG Simon, MC Yoon, SS AF Lee, Hae-June Yoon, Changhwan Park, Do Jooong kim, Yeo-Jung Schmidt, Benjamin Lee, Yoon-Jin Tap, William D. Eisinger-Mathason, T. S. Karin Choy, Edwin Kirsch, David G. Simon, M. Celeste Yoon, Sam S. TI Inhibition of Vascular Endothelial Growth Factor A and Hypoxia-Inducible Factor 1 alpha Maximizes the Effects of Radiation in Sarcoma Mouse Models Through Destruction of Tumor Vasculature SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID STEREOTACTIC BODY RADIOTHERAPY; INTENSITY-MODULATED RADIOTHERAPY; IMAGE-GUIDED RADIOTHERAPY; IONIZING-RADIATION; PROSTATE-CANCER; FREE-RADICALS; CARCINOMA; CELLS; HIF-1; RADIOSENSITIVITY AB Purpose: To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1 alpha (HIF-1 alpha) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie trimodality therapy) for soft-tissue sarcoma. Methods and Materials: Hypoxia-inducible factor 1 alpha was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1 alpha binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines. Results: In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm(3) within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1 alpha inhibition kept tumors at < 250 mm(3) for up to 30 days. Trimodality therapy on tumors reduced HIF-1 alpha activity as measured by expression of nuclear HIF-1 alpha by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2-to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and gamma H2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays. Conclusions: Inhibition of HIF-1 alpha is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature. (C) 2015 Elsevier Inc. C1 [Lee, Hae-June; Schmidt, Benjamin; Lee, Yoon-Jin] Massachusetts Gen Hosp, Dept Surg, Harvard Med Sch, Boston, MA 02114 USA. [Choy, Edwin] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lee, Hae-June] Korea Inst Radiol & Med Sci, Divis Radiat Effects, Seoul, South Korea. [Yoon, Changhwan; Park, Do Jooong; Yoon, Sam S.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Tap, William D.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Park, Do Jooong] Seoul Natl Univ, Bundang Hosp, Dept Surg, Seoul 151, South Korea. [kim, Yeo-Jung; Eisinger-Mathason, T. S. Karin; Simon, M. Celeste] Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Kirsch, David G.] Duke Univ Med Ctr, Dept Canc Biol, Durham, NC USA. [Kirsch, David G.] Duke Univ Med Ctr, Dept Pharmacol, Durham, NC USA. [Kirsch, David G.] Duke Univ Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Simon, M. Celeste] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Lee, HJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Harvard Med Sch, Boston, MA 02114 USA. FU National Institutes of Health [1R21 CA117128-02, 1R01 CA158301-01]; Society for Surgical Oncology Clinical Investigator Award FX Supported by National Institutes of Health grants 1R21 CA117128-02 (to S.S.Y.) and 1R01 CA158301-01 (to S.S.Y. and M.C.S.) and a Society for Surgical Oncology Clinical Investigator Award (to S.S.Y.). NR 31 TC 1 Z9 2 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2015 VL 91 IS 3 BP 621 EP 630 DI 10.1016/j.ijrobp.2014.10.047 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CA8YJ UT WOS:000349206600022 PM 25544668 ER PT J AU Fan, OM Camp, M Mantzoros, CS AF Fan, Olivia M. Camp, Michelle Mantzoros, Christos S. TI New research developments and insights from Metabolism SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID HIGH-FAT DIET; BROWN ADIPOSE-TISSUE; INSULIN-RESISTANCE; IRISIN LEVELS; POSTPRANDIAL GLUCOSE; RANDOMIZED CROSSOVER; CALORIC RESTRICTION; OBESE INDIVIDUALS; DNA METHYLATION; CLINICAL-TRIAL C1 [Fan, Olivia M.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Div Endocrinol, Boston, MA USA. [Fan, Olivia M.; Camp, Michelle; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Endocrinol Sect, Boston, MA 02215 USA. RP Fan, OM (reprint author), VA Boston Healthcare Syst, Div Endocrinol, 9-B 150 S Huntington Ave, Boston, MA 02130 USA. EM Olivia.Farr@va.gov OI Farr, Olivia/0000-0002-5182-3432 NR 60 TC 0 Z9 0 U1 0 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD MAR PY 2015 VL 64 IS 3 BP 354 EP 367 DI 10.1016/j.metabol.2014.12.002 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CA2QO UT WOS:000348752700002 ER PT J AU Gjini, E Mansour, MR Sander, JD Moritz, N Nguyen, AT Kesarsing, M Gans, E He, SN Chen, S Ko, M Kuang, YY Yang, S Zhou, Y Rodig, S Zon, LI Joung, JK Rao, A Look, AT AF Gjini, Evisa Mansour, Marc R. Sander, Jeffry D. Moritz, Nadine Nguyen, Ashley T. Kesarsing, Michiel Gans, Emma He, Shuning Chen, Si Ko, Myunggon Kuang, You-Yi Yang, Song Zhou, Yi Rodig, Scott Zon, Leonard I. Joung, J. Keith Rao, Anjana Look, A. Thomas TI A Zebrafish Model of Myelodysplastic Syndrome Produced through tet2 Genomic Editing SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; MUTANT TET2; IN-VIVO; MUTATIONS; DNA; DIFFERENTIATION; MALIGNANCIES; TRANSPLANTATION; MYELOFIBROSIS AB The ten-eleven translocation 2 gene (TET2) encodes a member of the TET family of DNA methylcytosine oxidases that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to initiate the demethylation of DNA within genomic CpG islands. Somatic loss-of-function mutations of TET2 are frequently observed in human myelodysplastic syndrome (MDS), which is a clonal malignancy characterized by dysplastic changes of developing blood cell progenitors, leading to ineffective hematopoiesis. We used genome-editing technology to disrupt the zebrafish Tet2 catalytic domain. tet2(m/m) (homozygous for the mutation) zebrafish exhibited normal embryonic and larval hematopoiesis but developed progressive clonal myelodysplasia as they aged, culminating in myelodysplastic syndromes (MDS) at 24 months of age, with dysplasia of myeloid progenitor cells and anemia with abnormal circulating erythrocytes. The resultant tet2(m/m) mutant zebrafish lines show decreased levels of 5hmC in hematopoietic cells of the kidney marrow but not in other cell types, most likely reflecting the ability of other Tet family members to provide this enzymatic activity in nonhematopoietic tissues but not in hematopoietic cells. tet2(m/m) zebrafish are viable and fertile, providing an ideal model to dissect altered pathways in hematopoietic cells and, for small-molecule screens in embryos, to identify compounds with specific activity against tet2 mutant cells. C1 [Gjini, Evisa; Mansour, Marc R.; Moritz, Nadine; Nguyen, Ashley T.; Kesarsing, Michiel; Gans, Emma; He, Shuning; Chen, Si; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Gjini, Evisa; Mansour, Marc R.; Moritz, Nadine; Nguyen, Ashley T.; Kesarsing, Michiel; Gans, Emma; He, Shuning; Chen, Si; Look, A. Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, Charlestown, MA USA. [Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ko, Myunggon; Rao, Anjana] La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA USA. [Kuang, You-Yi] Chinese Acad Fishery Sci 232, Heilongjiang River Fisheries Res Inst, Harbin, Heilongjiang, Peoples R China. [Yang, Song; Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Yang, Song; Zhou, Yi; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mansour, Marc R.] UCL, UCL Canc Inst, Dept Hematol, London, England. [Rodig, Scott] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu FU National Cancer Institute, National Institutes of Health [R01 CA93152] FX This work was supported by the National Cancer Institute, National Institutes of Health (grant R01 CA93152 to A. T. L.); by a Leukemia and Lymphoma Society Special Fellow Award (to E. G.); by an Alex's Lemonade Stand Foundation Young Investigator Award (to E. G.); by the Andrew McDonough B ~ Foundation (to E. G.); by an NIH Director's Pioneer Award (DP1 GM105378 to J. K. J.); by the National Institute of General Medical Science, NIH (R01 GM088040 to J. K. J.); and by the National Cancer Institute, NIH (T32 CA009216 to J. D. S.). NR 50 TC 14 Z9 15 U1 4 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2015 VL 35 IS 5 BP 789 EP 804 DI 10.1128/MCB.00971-14 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CB0FE UT WOS:000349300200003 PM 25512612 ER PT J AU Wende, AR O'Neill, BT Bugger, H Riehle, C Tuinei, J Buchanan, J Tsushima, K Wang, L Caro, P Guo, A Sloan, C Kim, BJ Wang, XH Pereira, RO McCrory, MA Nye, BG Benavides, GA Darley-Usmar, VM Shioi, T Weimer, BC Abel, ED AF Wende, Adam R. O'Neill, Brian T. Bugger, Heiko Riehle, Christian Tuinei, Joseph Buchanan, Jonathan Tsushima, Kensuke Wang, Li Caro, Pilar Guo, Aili Sloan, Crystal Kim, Bum Jun Wang, Xiaohui Pereira, Renata O. McCrory, Mark A. Nye, Brenna G. Benavides, Gloria A. Darley-Usmar, Victor M. Shioi, Tetsuo Weimer, Bart C. Abel, E. Dale TI Enhanced Cardiac Akt/Protein Kinase B Signaling Contributes to Pathological Cardiac Hypertrophy in Part by Impairing Mitochondrial Function via Transcriptional Repression of Mitochondrion-Targeted Nuclear Genes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; CHRONIC AKT ACTIVATION; FATTY-ACID OXIDATION; RECEPTOR ERR-ALPHA; HEART-FAILURE; PRESSURE-OVERLOAD; CARDIOVASCULAR-SYSTEM; GLUCOSE-UPTAKE; GROWTH-FACTOR; STRIPED BASS AB Sustained Akt activation induces cardiac hypertrophy (LVH), which may lead to heart failure. This study tested the hypothesis that Akt activation contributes to mitochondrial dysfunction in pathological LVH. Akt activation induced LVH and progressive repression of mitochondrial fatty acid oxidation (FAO) pathways. Preventing LVH by inhibiting mTOR failed to prevent the decline in mitochondrial function, but glucose utilization was maintained. Akt activation represses expression of mitochondrial regulatory, FAO, and oxidative phosphorylation genes in vivo that correlate with the duration of Akt activation in part by reducing FOXO-mediated transcriptional activation of mitochondrion-targeted nuclear genes in concert with reduced signaling via peroxisome proliferator-activated receptor alpha (PPAR alpha)/PGC-1 alpha and other transcriptional regulators. In cultured myocytes, Akt activation disrupted mitochondrial bioenergetics, which could be partially reversed by maintaining nuclear FOXO but not by increasing PGC-1 alpha. Thus, although short-term Akt activation may be cardioprotective during ischemia by reducing mitochondrial metabolism and increasing glycolysis, long-term Akt activation in the adult heart contributes to pathological LVH in part by reducing mitochondrial oxidative capacity. C1 [Wende, Adam R.; O'Neill, Brian T.; Bugger, Heiko; Riehle, Christian; Tuinei, Joseph; Buchanan, Jonathan; Tsushima, Kensuke; Wang, Li; Caro, Pilar; Guo, Aili; Sloan, Crystal; Kim, Bum Jun; Wang, Xiaohui; Pereira, Renata O.; Abel, E. Dale] Univ Utah, Sch Med, Program Mol Med, Salt Lake City, UT 84105 USA. [Wende, Adam R.; O'Neill, Brian T.; Bugger, Heiko; Riehle, Christian; Tuinei, Joseph; Buchanan, Jonathan; Tsushima, Kensuke; Wang, Li; Caro, Pilar; Guo, Aili; Sloan, Crystal; Kim, Bum Jun; Wang, Xiaohui; Pereira, Renata O.; Abel, E. Dale] Univ Utah, Sch Med, Div Endocrinol Metab & Diabet, Salt Lake City, UT USA. [Wende, Adam R.; McCrory, Mark A.; Nye, Brenna G.; Benavides, Gloria A.; Darley-Usmar, Victor M.] Univ Alabama Birmingham, Dept Pathol, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [O'Neill, Brian T.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Integrat Physiol & Metab, Boston, MA 02115 USA. [Bugger, Heiko] Univ Freiburg, Heart Ctr Cardiol & Angiol 1, D-79106 Freiburg, Germany. [Riehle, Christian; Tsushima, Kensuke; Pereira, Renata O.; Abel, E. Dale] Univ Iowa, Fraternal Order Eagles Diabet Res Ctr, Iowa City, IA USA. [Riehle, Christian; Tsushima, Kensuke; Pereira, Renata O.; Abel, E. Dale] Univ Iowa, Roy J & Lucille Carver Coll Med, Div Endocrinol & Metab, Iowa City, IA USA. [Guo, Aili] Ohio Univ, Heritage Coll Osteopath Med Specialty Med, Inst Diabet, Athens, OH 45701 USA. [Shioi, Tetsuo] Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto, Japan. [Weimer, Bart C.] Univ Calif Davis, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. RP Abel, ED (reprint author), Univ Utah, Sch Med, Program Mol Med, Salt Lake City, UT 84105 USA. EM DRCAdmin@uiowa.edu FU National Institutes of Health (NIH) [R01HL070070, R01DK092065, U01HL70525]; American Diabetes Association; JDRF [10-2009-672]; NIH [K99R00 HL111322, T32 HL007576]; German Research Foundation (DFG); Spanish Ministry of Education and Science; AHA, Western Affiliates FX This work was supported by grants R01HL070070, R01DK092065, and U01HL70525 from the National Institutes of Health (NIH) to E.D.A., an Established Investigator of the American Heart Association (AHA). B.T.O. was supported by a physician scientist-training award from the American Diabetes Association; A.R.W. was supported by a postdoctoral fellowship from the JDRF (10-2009-672) and NIH K99R00 HL111322. H.B. and C.R. were supported by postdoctoral fellowships from the German Research Foundation (DFG), P.C. was supported by a predoctoral fellowship from the Spanish Ministry of Education and Science, and R.O.P. was supported by a postdoctoral fellowship from the AHA, Western Affiliates, and T32 HL007576 from the NIH. NR 65 TC 12 Z9 13 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2015 VL 35 IS 5 BP 831 EP 846 DI 10.1128/MCB.01109-14 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CB0FE UT WOS:000349300200006 PM 25535334 ER PT J AU Haddad, RI Chan, ATC Vermorken, JB AF Haddad, Robert I. Chan, Anthony T. C. Vermorken, Jan B. TI Barriers to clinical trial recruitment in head and neck cancer SO ORAL ONCOLOGY LA English DT Review DE Head and neck; Trials; Recruitment; Barriers ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; HUMAN-PAPILLOMAVIRUS; CHEMOTHERAPY; SURVIVAL; IMPACT; GUIDELINES; DIAGNOSIS; COUNTRIES; PROGRAM AB Despite substantial improvements in the treatment of head and neck cancer (HNC) over the last two decades, overall survival rates remain unsatisfactory. The need for improved therapeutic approaches for HNC patients is hampered by low patient recruitment rates in HNC clinical trials, particularly Phase III studies. Based on an analysis of ClinicalTrials.gov, this article identified several potential barriers to patient recruitment in Phase I-III clinical trials of treatments for HNC. Of 694 HNC trials identified on ClinicalTrials.gov from multiple sites worldwide, 91 (13.1%) were identified as either terminated, suspended or withdrawn; 27.5% (n = 25) of these did not provide an additional reason for stopping recruitment early. Insufficient accrual was the most common reason provided for trial closure (n = 23, 25.3%). Possible reasons for the insufficient accrual rates include the inappropriate designs of these studies given the change in HNC tumour biology in the last 20 years, the low incidence of the disease, and the diversity of treatment standards and referral processes across countries. Given the low numbers of drugs approved for HNC, it is important that barriers to recruitment in this field are addressed to allow new therapies to be successfully validated in completed clinical trials. This review discusses how these accrual challenges may be overcome with changes to clinical trial designs, including their adaptation to specific subgroups, such as human papillomavirus-positive patients. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Haddad, Robert I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02215 USA. [Chan, Anthony T. C.] Chinese Univ Hong Kong, Sir Y K Pao Ctr Canc, Hong Kong Canc Inst, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China. [Vermorken, Jan B.] Univ Antwerp Hosp, Dept Med Oncol, B-2650 Edegem, Belgium. RP Haddad, RI (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, 450 Brookline Ave, Boston, MA 02215 USA. EM robert_haddad@dfci.harvard.edu; anthony@clo.cuhk.edu.hk; jan.b.vermorken@uza.be FU Boehringer Ingelheim FX This work was supported by Boehringer Ingelheim. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Sophie Albon, of Ogilvy Healthworld, and Katie McClendon of GeoMed, part of the KnowledgePoint360 Group, an Ashfield company, during the preparation of this manuscript. NR 52 TC 3 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD MAR PY 2015 VL 51 IS 3 BP 203 EP 211 DI 10.1016/j.oraloncology.2014.12.007 PG 9 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA CA7FZ UT WOS:000349084500003 PM 25593017 ER PT J AU Sheu, J Saavedra, AP Degar, BA Duncan, CN Fawaz, R Tan, JK Schmidt, BA Kim, HB Huang, JT AF Sheu, Johanna Saavedra, Arturo P. Degar, Barbara A. Duncan, Christine N. Fawaz, Rima Tan, Jennifer K. Schmidt, Birgitta A. Kim, Heung B. Huang, Jennifer T. TI Bone marrow engraftment and associated dermatologic sequelae in a three-yr-old after liver transplantation SO PEDIATRIC TRANSPLANTATION LA English DT Article DE chimerism; liver transplantation; bone marrow engraftment; post-transplant; autoimmune; Langerhans cell histiocytosis ID VERSUS-HOST-DISEASE; CELL TRANSPLANTATION; CHIMERISM; ALLOGRAFTS; TOLERANCE; RECIPIENT; VITILIGO AB We present a case of a three-yr-old child with a history of multisystem Langerhans cell histiocytosis treated with systemic chemotherapy, who developed progressive liver failure and received an orthotopic split liver transplant while continuing on chemotherapy. Onemonth following transplant, he developed acute graft-vs.-host disease of the skin and gastrointestinal tract. Peripheral blood chimerism studies post-transplant demonstrated an increasing predominance of donor lymphocytes and granulocytes. Shortly after, the patient developed vitiligo, and twoyr after transplantation, the patient developed skin manifestations of psoriasis. We discuss and review the current literature, which demonstrates that chimerism following liver transplantation is rare and in our patient may be related to his profound immunosuppression around the time of liver transplant as well the development of acute graft-versus-host disease. While autoimmune disease can occur after solid organ and stem cell transplant, our patient developed skin manifestations of autoimmunity after liver transplantation, which is also rarely described. C1 [Sheu, Johanna] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Saavedra, Arturo P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Degar, Barbara A.] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Pediat,Dana Farber Canc Inst, Boston, MA 02115 USA. [Duncan, Christine N.] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Med,Dana Farber Canc Inst, Boston, MA 02115 USA. [Fawaz, Rima] Harvard Univ, Boston Childrens Hosp, Sch Med, Div Gastroenterol Hepatol & Nutr, Boston, MA 02115 USA. [Tan, Jennifer K.] Harvard Univ, Brigham & Womens Hosp, Boston Childrens Hosp, Dept Dermatol,Med Sch, Boston, MA 02115 USA. [Schmidt, Birgitta A.] Harvard Univ, Boston Childrens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Kim, Heung B.] Harvard Univ, Boston Childrens Hosp, Dept Surg, Sch Med, Boston, MA 02115 USA. [Huang, Jennifer T.] Harvard Univ, Boston Childrens Hosp, Sch Med, Dermatol Program, Boston, MA 02115 USA. RP Huang, JT (reprint author), Harvard Univ, Boston Childrens Hosp, Sch Med, Dermatol Program, 300 Longwood Ave, Boston, MA 02115 USA. EM jennifer.huang@childrens.harvard.edu NR 23 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1397-3142 EI 1399-3046 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD MAR PY 2015 VL 19 IS 2 BP E41 EP E46 DI 10.1111/petr.12412 PG 6 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA CA1EU UT WOS:000348656500003 PM 25516432 ER PT J AU Erlen, JA Tamres, LK Reynolds, N Golin, CE Rosen, MI Remien, RH Banderas, JW Schneiderman, N Wagner, G Bangsberg, DR Liu, HH AF Erlen, Judith A. Tamres, Lisa K. Reynolds, Nancy Golin, Carol E. Rosen, Marc I. Remien, Robert H. Banderas, Julie W. Schneiderman, Neil Wagner, Glenn Bangsberg, David R. Liu, Honghu TI Assessing Usual Care in Clinical Trials SO WESTERN JOURNAL OF NURSING RESEARCH LA English DT Article DE usual care; intervention; control condition; HIV; adherence ID ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED-CONTROLLED-TRIALS; ADHERENCE INTERVENTIONS AB Researchers designing clinical trials often specify usual care received by participants as the control condition expecting that all participants receive usual care regardless of group assignment. The assumption is that the groups in the study are affected similarly. We describe the assessment of usual care within the 16 studies in Multisite Adherence Collaboration in HIV (MACH 14), a multisite collaboration on adherence to antiretroviral therapy. Only five of the studies in MACH 14 assessed usual care. Assessment protocols varied as did the timing and frequency of assessments. All usual care assessments addressed patient education focused on HIV, HIV medications, and medication adherence. Our findings support earlier work that calls for systematic assessments of usual care within the study design, inclusion of descriptions of usual care in reports of the study, and the influence of usual care on the experimental condition in clinical trials. C1 [Erlen, Judith A.; Tamres, Lisa K.] Univ Pittsburgh, Pittsburgh, PA 15261 USA. [Reynolds, Nancy; Rosen, Marc I.] Yale Univ, New Haven, CT USA. [Golin, Carol E.] Univ N Carolina, Chapel Hill, NC USA. [Remien, Robert H.] Columbia Univ, New York, NY USA. [Banderas, Julie W.] Univ Missouri Kansas City, Sch Med, Kansas City, MO USA. [Schneiderman, Neil] Univ Miami, Coral Gables, FL 33124 USA. [Wagner, Glenn] RAND Corp, Santa Monica, CA USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Liu, Honghu] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Erlen, JA (reprint author), Univ Pittsburgh, Dept Hlth & Community Syst, Sch Nursing, 415 Victoria Bldg,3500 Victoria St, Pittsburgh, PA 15261 USA. EM jae001@pitt.edu FU Multisite Adherence Collaboration in HIV (MACH14) from the National Institute of Mental Health (NIMH), Office on AIDS [R01MH078773]; [R01DA11869]; [MH54907]; [2R01NR04749]; [R01NR04749]; [MH68197]; [R01 DA13826]; [K23MH01862]; [MH01584]; [R01 AI41413]; [R01 MH61173]; [NIH/NIAID AI38858]; [AI069419]; [K02 DA017277]; [R01DA15215]; [NIMH P01 MH49548]; [MH58986]; [RO1MH61695]; [CC99-SD003]; [CC02-SD-003]; [R01DA015679] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Multisite Adherence Collaboration in HIV (MACH14) Grant R01MH078773 from the National Institute of Mental Health (NIMH), Office on AIDS. The original grants of individual participating studies are R01DA11869, MH54907, 2R01NR04749, R01NR04749, MH68197, R01 DA13826, K23MH01862, MH01584, R01 AI41413, R01 MH61173, NIH/NIAID AI38858, AI069419, K02 DA017277, R01DA15215, NIMH P01 MH49548, MH58986, RO1MH61695, CC99-SD003, CC02-SD-003, and R01DA015679. NR 14 TC 2 Z9 2 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0193-9459 EI 1552-8456 J9 WESTERN J NURS RES JI West. J. Nurs. Res. PD MAR PY 2015 VL 37 IS 3 BP 288 EP 298 DI 10.1177/0193945914526001 PG 11 WC Nursing SC Nursing GA CA7MW UT WOS:000349102400002 PM 24622154 ER PT J AU Heinrich, M Burger, D Wang, LM Tahhan, G Reinhold, P Zhao, MH Hsu, E Warden, S Baum, D Faustman, DL AF Heinrich, Melanie Burger, Douglas Wang, Limei Tahhan, Georges Reinhold, Peter, III Zhao, Menghan Hsu, Elise Warden, Sarah Baum, Danielle Faustman, Denise L. TI TNFR1 and TNFR2 Expression and Induction on Human Treg Cells from Type 1 Diabetic Subjects SO ANTIBODIES LA English DT Article DE autoimmunity; T regulatory cells (Treg); type 1 diabetes; TNFR2 ID REGULATORY T-CELLS; TUMOR-NECROSIS-FACTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; CROHNS-DISEASE; ALPHA THERAPY; ETANERCEPT THERAPY; RECEPTOR; AUTOIMMUNITY AB Several autoimmune diseases are marked by a deficiency of soluble tumor necrosis factor (TNF). The TNF deficiency is caused in at least one autoimmune disease, multiple sclerosis, by an overabundance of TNF receptor 1 (TNFR1). Excess TNFR1 binds and inactivates TNF and this leaves less TNF bioavailable. This study sought to determine if expression of fresh or IL2-stimulated TNF receptors on Tregs cells, an important immunoregulatory cell involved in autoimmunity, is altered in type I diabetes. Standard fluorescence analysis was used to examine the levels of TNFR1 and TNFR2 on human Tregs in patients with type I diabetes (T1D) or controls. Fresh Tregs from T1D compared to control Tregs had identical levels of TNFR1. In marked contrast, Type 1 diabetic patients Treg cells had statistically elevated levels of TNFR2 compared to controls. Tregs stimulated with IL2 from both T1D and controls showed marked increase of TNFR2 expression in a dose-response manner, but the dose response increase in TNFR2 was significantly higher for T1D Treg cells. No IL2 dose-response was present for TNFR1 on either T1D or control Tregs exposed to IL2. A large study of serum for secreted levels of TNFR2 also revealed elevated circulating levels consistent with the elevated surface expression on Tregs. These findings suggest that abnormal regulation of TNFR2 expression with elevated cellular and secreted levels of TNFR2 is a characteristic of Type 1 diabetes. It is possible that the relative deficiency of TNF in type I diabetes, in contrast to multiple sclerosis, is caused by excess expression of TNFR such as TNFR2, a binding structure for inactivating TNF. C1 [Faustman, Denise L.] Massachusetts Gen Hosp, Immunobiol Labs, Bldg 149,13th St,Rm 3502, Boston, MA 02129 USA. Harvard Univ, Sch Med, Bldg 149,13th St,Rm 3502, Boston, MA 02129 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Immunobiol Labs, Bldg 149,13th St,Rm 3502, Boston, MA 02129 USA. EM faustman@helix.mgh.harvard.edu NR 31 TC 1 Z9 1 U1 1 U2 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2073-4468 J9 ANTIBODIES JI Antibodies PD MAR PY 2015 VL 4 IS 1 BP 34 EP 47 DI 10.3390/antib4010034 PG 14 WC Immunology SC Immunology GA DG1CN UT WOS:000371803000002 ER PT J AU Laviv, A Faquin, WC August, M AF Laviv, Amir Faquin, William C. August, Meredith TI Schwannoma (neurilemmoma) in the floor of the mouth: Presentation of two cases SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY MEDICINE AND PATHOLOGY LA English DT Article DE Shwannomas; Neurilemmoma; Floor of mouth ID NEEDLE-ASPIRATION-CYTOLOGY; SALIVARY-GLAND LESIONS; OF-THE-LITERATURE AB Schwannomas, also known as neurilemmomas, are uncommon neoplasms, derived from Schwann cells of the nerve sheath. Although rare in the oral cavity, Schwannomas should be considered in the differential diagnosis of intraoral masses. Floor of mouth tumors are especially unusual, and in this site, the main differential diagnosis is a minor salivary gland neoplasm. This article presents two cases of Schwannoma in this locale. (C) 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved. C1 [Laviv, Amir; August, Meredith] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [August, Meredith] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Laviv, A (reprint author), Fruit St,Warren 1201, Boston, MA 02114 USA. EM amirlaviv@gmail.com NR 12 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-5558 EI 2212-5566 J9 J ORAL MAXILLOFAC SU JI J. Oral Maxillofac. Surg. Med. Pathol. PD MAR PY 2015 VL 27 IS 2 BP 199 EP 203 DI 10.1016/j.ajoms.2013.09.004 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DF8GQ UT WOS:000371595900009 ER PT J AU Jensen, KDC Camejo, A Melo, MB Cordeiro, C Julien, L Grotenbreg, GM Frickel, EM Ploegh, HL Young, L Saeij, JPJ AF Jensen, Kirk D. C. Camejo, Ana Melo, Mariane B. Cordeiro, Cynthia Julien, Lindsay Grotenbreg, Gijsbert M. Frickel, Eva-Maria Ploegh, Hidde L. Young, Lucy Saeij, Jeroen P. J. TI Toxoplasma gondii Superinfection and Virulence during Secondary Infection Correlate with the Exact ROP5/ROP18 Allelic Combination SO MBIO LA English DT Article ID IMMUNITY-RELATED GTPASES; T-CELL RESPONSES; IRG RESISTANCE GTPASES; INDUCIBLE NITRIC-OXIDE; IFN-GAMMA PRODUCTION; MULTILOCUS PCR-RFLP; OCULAR TOXOPLASMOSIS; CONGENITAL TOXOPLASMOSIS; PROTECTIVE IMMUNITY; PSEUDOKINASE ROP5 AB The intracellular parasite Toxoplasma gondii infects a wide variety of vertebrate species globally. Infection in most hosts causes a lifelong chronic infection and generates immunological memory responses that protect the host against new infections. In regions where the organism is endemic, multiple exposures to T. gondii likely occur with great frequency, yet little is known about the interaction between a chronically infected host and the parasite strains from these areas. A widely used model to explore secondary infection entails challenge of chronically infected or vaccinated mice with the highly virulent type I RH strain. Here, we show that although vaccinated or chronically infected C57BL/6 mice are protected against the type I RH strain, they are not protected against challenge with most strains prevalent in South America or another type I strain, GT1. Genetic and genomic analyses implicated the parasite-secreted rhoptry effectors ROP5 and ROP18, which antagonize the host's gamma interferon-induced immunity-regulated GTPases (IRGs), as primary requirements for virulence during secondary infection. ROP5 and ROP18 promoted parasite superinfection in the brains of challenged survivors. We hypothesize that superinfection may be an important mechanism to generate T. gondii strain diversity, simply because two parasite strains would be present in a single meal consumed by the feline definitive host. Superinfection may drive the genetic diversity of Toxoplasma strains in South America, where most isolates are IRG resistant, compared to North America, where most strains are IRG susceptible and are derived from a few clonal lineages. In summary, ROP5 and ROP18 promote Toxoplasma virulence during reinfection. IMPORTANCE Toxoplasma gondii is a widespread parasite of warm-blooded animals and currently infects one-third of the human population. A long-standing assumption in the field is that prior exposure to this parasite protects the host from subsequent reexposure, due to the generation of protective immunological memory. However, this assumption is based on clinical data and mouse models that analyze infections with strains common to Europe and North America. In contrast, we found that the majority of strains sampled from around the world, in particular those from South America, were able to kill or reinfect the brains of hosts previously exposed to T. gondii. The T. gondii virulence factors ROP5 and ROP18, which inhibit key host effectors that mediate parasite killing, were required for these phenotypes. We speculate that these results underpin clinical observations that pregnant women previously exposed to Toxoplasma can develop congenital infection upon reexposure to South American strains. C1 [Jensen, Kirk D. C.; Camejo, Ana; Melo, Mariane B.; Cordeiro, Cynthia; Julien, Lindsay; Saeij, Jeroen P. J.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Grotenbreg, Gijsbert M.] Natl Univ Singapore, Dept Microbiol, Dept Biol Sci, Singapore 117548, Singapore. [Grotenbreg, Gijsbert M.] Natl Univ Singapore, Inst Life Sci, Immunol Programme, Singapore 117548, Singapore. [Frickel, Eva-Maria] MRC Natl Inst Med Res, Div Parasitol, London, England. [Ploegh, Hidde L.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Ploegh, Hidde L.] MIT, Cambridge, MA 02139 USA. [Young, Lucy] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Saeij, JPJ (reprint author), MIT, Dept Biol, Cambridge, MA 02139 USA. EM jsaeij@mit.edu RI Melo, Mariane/A-1975-2013; OI Saeij, Jeroen/0000-0003-0289-7109 FU Medical Research Council [MC_UP_1202/12]; NIAID NIH HHS [R01 AI080621] NR 104 TC 3 Z9 4 U1 3 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAR-APR PY 2015 VL 6 IS 2 AR e02280-14 DI 10.1128/mBio.02280-14 PG 15 WC Microbiology SC Microbiology GA CJ2KE UT WOS:000355312400038 PM 25714710 ER PT J AU Bispo, PJM Haas, W Gilmore, MS AF Bispo, Paulo J. M. Haas, Wolfgang Gilmore, Michael S. TI Biofilms in Infections of the Eye SO PATHOGENS LA English DT Review DE biofilm; eye; ocular infections; postoperative ocular infections; device-related ocular infections ID INTRAOCULAR-LENS MATERIAL; COAGULASE-NEGATIVE STAPHYLOCOCCI; ANTERIOR-CHAMBER CONTAMINATION; SCANNING-ELECTRON-MICROSCOPY; SOFT CONTACT-LENS; CRYSTALLINE KERATOPATHY; MICROBIAL KERATITIS; CATARACT-SURGERY; PSEUDOMONAS-AERUGINOSA; IN-VITRO AB The ability to form biofilms in a variety of environments is a common trait of bacteria, and may represent one of the earliest defenses against predation. Biofilms are multicellular communities usually held together by a polymeric matrix, ranging from capsular material to cell lysate. In a structure that imposes diffusion limits, environmental microgradients arise to which individual bacteria adapt their physiologies, resulting in the gamut of physiological diversity. Additionally, the proximity of cells within the biofilm creates the opportunity for coordinated behaviors through cell-cell communication using diffusible signals, the most well documented being quorum sensing. Biofilms form on abiotic or biotic surfaces, and because of that are associated with a large proportion of human infections. Biofilm formation imposes a limitation on the uses and design of ocular devices, such as intraocular lenses, posterior contact lenses, scleral buckles, conjunctival plugs, lacrimal intubation devices and orbital implants. In the absence of abiotic materials, biofilms have been observed on the capsule, and in the corneal stroma. As the evidence for the involvement of microbial biofilms in many ocular infections has become compelling, developing new strategies to prevent their formation or to eradicate them at the site of infection, has become a priority. C1 [Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Microbiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Immunol, Boston, MA 02114 USA. RP Gilmore, MS (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM michael_gilmore@meei.harvard.edu FU NEI NIH HHS [R01 EY024285]; NIAID NIH HHS [P01 AI083214] NR 157 TC 6 Z9 6 U1 2 U2 15 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2076-0817 J9 PATHOGENS JI Pathogens PD MAR PY 2015 VL 4 IS 1 BP 111 EP 136 DI 10.3390/pathogens4010111 PG 26 WC Microbiology SC Microbiology GA DG0YJ UT WOS:000371791800006 PM 25806622 ER PT J AU Chang, ET Wells, KB Gilmore, J Tang, LQ Morgan, AU Sanders, S Chung, BW AF Chang, Evelyn T. Wells, Kenneth B. Gilmore, James Tang, Lingqi Morgan, Anna U. Sanders, Starr Chung, Bowen TI Comorbid Depression and Substance Abuse Among Safety-Net Clients in Los Angeles: A Community Participatory Study SO PSYCHIATRIC SERVICES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY MEDICAL-CARE; MENTAL-HEALTH-SERVICES; USE DISORDERS; COOCCURRING DISORDERS; PSYCHIATRIC-DISORDERS; HOMELESS ADULTS; EMERGENCY-DEPARTMENT; HOSPITAL UTILIZATION; ALCOHOL AB Objective: Depression and substance abuse are common among low-income adults from racial-ethnic minority groups who receive services in safety-net settings, although little is known about how clients differ by service setting. This study examined characteristics and service use among depressed, low-income persons from minority groups in under-resourced communities who did and did not have a substance abuse history. Methods: The study used cross-sectional baseline client data (N= 957) from Community Partners in Care, an initiative to improve depression services in Los Angeles County. Clients with probable depression (eight-item Patient Health Questionnaire) from substance abuse programs were compared with depressed clients with and without a history of substance abuse from primary care, mental health, and social and community programs. Sociodemographic, health status, and services utilization variables were examined. Results: Of the 957 depressed clients, 217 (23%) were from substance abuse programs; 269 (28%) clients from other sectors had a substance abuse history, and 471 (49%) did not. Most clients from substance abuse programs or with a substance abuse history were unemployed and impoverished, lacked health insurance, and had high rates of arrests and homelessness. They were also more likely than clients without a substance abuse history to have depression or anxiety disorders, psychosis, and mania and to use emergency rooms. Conclusions: Clients with depression and a substance abuse history had significant psychosocial stressors and high rates of service use, which suggests that communitywide approaches may be needed to address both depression and substance abuse in this safety-net population. C1 [Chang, Evelyn T.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Gen Internal Med, Los Angeles, CA USA. [Wells, Kenneth B.; Tang, Lingqi; Chung, Bowen] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. [Wells, Kenneth B.; Chung, Bowen] RAND Corp, Santa Monica, CA 90406 USA. [Gilmore, James] Behav Hlth Serv Inc, Los Angeles, CA USA. [Morgan, Anna U.] Harbor UCLA Med Ctr, Div Gen Internal Med, Los Angeles, CA USA. [Sanders, Starr] House Uhuru, Los Angeles, CA USA. RP Chang, ET (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Gen Internal Med, Los Angeles, CA USA. EM evelynchang.md@gmail.com FU Office of Academic Affiliations, Health Services Research and Development, U.S. Department of Veterans Affairs (VA) [TMP 65-020]; National Institute of Mental Health (NIMH) [R01MH078853, P30MH082760, P30MH068639]; Robert Wood Johnson Foundation [64244]; UCLA Clinical and Translational Science Institute, National Center for Advancing Translational Science [UL1TR000124]; California Community Foundation [CMCH-12-97088] FX Funding was provided through the Health Services Fellowship Training Program (TMP 65-020) by the Office of Academic Affiliations, Health Services Research and Development, U.S. Department of Veterans Affairs (VA). The study was also funded by awards R01MH078853, P30MH082760, and P30MH068639 from the National Institute of Mental Health (NIMH); award 64244 from the Robert Wood Johnson Foundation; award UL1TR000124 from the UCLA Clinical and Translational Science Institute, National Center for Advancing Translational Science; and award CMCH-12-97088 from the California Community Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the VA; NIMH; National Institutes of Health; UCLA Clinical and Translational Science Institute, National Center for Advancing Translational Science; California Community Foundation; or other affiliated institutions. Community Partners in Care is registered at clinical trials. gov (NCT01699789). The authors thank the 50 participating agencies and their representatives, the participating Los Angeles programs and their providers and staff, and the clients who participated. A list of community partners is at www.communitypartnersincare.org/about/partners. The authors thank the RAND Survey Research Group and trained community members who conducted client data collection. They also thank Wayne Aoki, Ph.D., for comments on the manuscript. NR 75 TC 0 Z9 0 U1 5 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2015 VL 66 IS 3 BP 285 EP 294 DI 10.1176/appi.ps.201300318 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE5QL UT WOS:000370686200011 PM 25727117 ER PT J AU Gifford, E Tavakoli, S Wisdom, J Hamlett-Berry, K AF Gifford, Elizabeth Tavakoli, Sara Wisdom, Jennifer Hamlett-Berry, Kim TI Implementation of Smoking Cessation Treatment in VHA Substance Use Disorder Residential Treatment Programs SO PSYCHIATRIC SERVICES LA English DT Article ID NICOTINE REPLACEMENT THERAPY; TOBACCO DEPENDENCE; ABUSE-TREATMENT; CIGARETTE-SMOKING; TREATMENT ORGANIZATIONS; ALCOHOL DEPENDENCE; PARIHS FRAMEWORK; UNITED-STATES; HEALTH; TRIAL AB Objectives: Although the prevalence of tobacco use among individuals with substance use disorders remains high, smoking cessation (SC) has not been a focus of addiction treatment programs. Veterans Health Administration (VHA) policy requires tobacco use screening and the availability of evidence-based SC treatment in specialty care settings, including substance use disorder programs. As part of a larger quality improvement effort, this qualitative study examined how SC treatment is delivered in VHA substance use disorder residential treatment programs (SRTPs) and the barriers and opportunities for growth that exist within these settings. Methods: Twenty-five staff were interviewed across a sample of 15 SRTPs. Participants were asked to describe their knowledge and attitudes about SC treatment as well as organizational barriers and facilitators related to implementation of SC treatment in their programs. Content analysis was used to extract responses within and across programs. Results: Participants endorsed SC as a general goal and reported that SRTPs responded to patients who requested help. However, many programs did not emphasize SC as an important part of recovery from substance use disorders and did not document, reevaluate, or consistently address tobacco use. Conclusions: The results identified critical gaps in the provision of SC treatment in VHA SRTPs. These findings suggest actionable opportunities to improve SC treatment in SRTPs, including providing training opportunities, developing or enforcing policies that support SC, implementing systems to track and report tobacco-related diagnoses and treatment, and obtaining leadership support for building a culture that encourages SC. C1 [Gifford, Elizabeth; Tavakoli, Sara] US Dept Vet Affairs Palo Alto Hlth Care Syst, Subst Use Disorder Qual Enhancement Res Initiat, Menlo Pk, CA USA. [Wisdom, Jennifer] George Washington Univ, Dept Hlth Policy, Milken Inst, Sch Publ Hlth, Washington, DC USA. [Wisdom, Jennifer] George Washington Univ, Off Vice President Res, Washington, DC USA. [Hamlett-Berry, Kim] US Dept Vet Affairs, Dept Clin Publ Hlth, Washington, DC USA. RP Gifford, E (reprint author), US Dept Vet Affairs Palo Alto Hlth Care Syst, Subst Use Disorder Qual Enhancement Res Initiat, Menlo Pk, CA USA. EM elizabeth.gifford@va.gov FU Office of Tobacco and Health: Policy and Programs, U.S. Department of Veterans Affairs (VA) Office of Clinical Public Health; Substance Use Disorders Quality Enhancement Initiative Center [QLP 59-030] FX This project was supported by the Office of Tobacco and Health: Policy and Programs, U.S. Department of Veterans Affairs (VA) Office of Clinical Public Health and by Locally Initiated Project QLP 59-030 from the Substance Use Disorders Quality Enhancement Initiative Center. The views expressed are those of the authors and do not necessarily reflect the views of the VA or any other entity of the U.S. Government. NR 56 TC 5 Z9 5 U1 4 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2015 VL 66 IS 3 BP 295 EP 302 DI 10.1176/appi.ps.201400008 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE5QL UT WOS:000370686200012 PM 25727118 ER PT J AU Montgomery, AE Dichter, ME Thomasson, AM Roberts, CB Byrne, T AF Montgomery, Ann Elizabeth Dichter, Melissa E. Thomasson, Arwin M. Roberts, Christopher Brent Byrne, Thomas TI Disparities in Housing Status Among Veterans With General Medical, Cognitive, and Behavioral Health Conditions SO PSYCHIATRIC SERVICES LA English DT Article ID HOMELESS VETERANS; CARE; GENDER; NEEDS; WOMEN AB Objective: The study explored disparities in housing status among veterans with general medical, cognitive, and behavioral health conditions. Methods: Multinomial mixed-effects models estimated the relationship between medical, cognitive, and behavioral health comorbidities and housing instability among veterans enrolled in the Veterans Health Administration (VHA) (N=1,582,125) who responded to the Homelessness Screening Clinical Reminder for homelessness and risk during a three-month period. Results: Veterans were two or more times as likely to screen positive for homelessness or risk if they had a diagnosis of a cognitive or behavioral health conditions in the study. Findings related to general medical conditions were inconsistent. Conclusions: The study found disparities in housing instability among VHA outpatients with cognitive and behavioral health conditions, suggesting the need to identify veterans with these conditions experiencing housing instability and the need to develop appropriate interventions to mitigate homelessness or risk. C1 [Montgomery, Ann Elizabeth] Philadelphia Dept Vet Affairs Med Ctr, Natl Ctr Homelessness Vet, Philadelphia, PA USA. [Dichter, Melissa E.; Thomasson, Arwin M.; Roberts, Christopher Brent] Philadelphia Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Byrne, Thomas] Boston Univ, Sch Social Work, Boston, MA 02215 USA. RP Montgomery, AE (reprint author), Philadelphia Dept Vet Affairs Med Ctr, Natl Ctr Homelessness Vet, Philadelphia, PA USA. EM ann.montgomery2@va.gov FU U.S. Department of Veterans Affairs (VA), National Center on Homelessness Among Veterans; VA Center for Health Equity Research and Promotion [LIP 72-061] FX This study was funded by the U.S. Department of Veterans Affairs (VA), National Center on Homelessness Among Veterans and a Competitive Pilot Research Grant (LIP 72-061) by the VA Center for Health Equity Research and Promotion. The contents of this article do not necessarily represent the views of the VA or the United States Government. NR 15 TC 1 Z9 1 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2015 VL 66 IS 3 BP 317 EP 320 DI 10.1176/appi.ps.201400014 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE5QL UT WOS:000370686200016 PM 25727122 ER PT J AU MacLaurin, SA Henderson, DC Freudenreich, O AF MacLaurin, Sarah A. Henderson, David C. Freudenreich, Oliver TI Delineating Responsibility: Primary Care Provider Perspective SO PSYCHIATRIC SERVICES LA English DT Letter ID MENTAL-ILLNESS C1 [MacLaurin, Sarah A.] Freedom Trail Clin, Erich Lindemann Mental Hlth Ctr, Boston, MA USA. [Henderson, David C.; Freudenreich, Oliver] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Henderson, David C.; Freudenreich, Oliver] Harvard Univ, Sch Med, Boston, MA USA. RP MacLaurin, SA (reprint author), Freedom Trail Clin, Erich Lindemann Mental Hlth Ctr, Boston, MA USA. FU Envivo; Janssen; Novartis; Otsuka; Beacon Health Strategies; Forum; Global Medical Education; Med-IQ; Oakstone Medical Education; Optimal Medicine; Psychogenics; UpToDate FX Ms. MacLaurin participates in the Kraft Center for Community Health's Practitioner Program, which pays 20% of her time, specified for projects benefiting the health center. Dr. Henderson has received research funds from or has served as a consultant to Envivo, Janssen, Novartis, and Otsuka. Dr. Freudenreich has received research funds or honoraria from or has served as a consultant to Beacon Health Strategies, Forum, Global Medical Education, Med-IQ, Oakstone Medical Education, Optimal Medicine, Psychogenics, and UpToDate. NR 4 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2015 VL 66 IS 3 BP 333 EP 333 DI 10.1176/appi.ps.660305 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE5QL UT WOS:000370686200025 PM 25727131 ER PT J AU Ichinose, F Zapol, WM AF Ichinose, Fumito Zapol, Warren M. TI Kenneth D. Bloch, MD (1956-2014) OBITUARY SO PULMONARY CIRCULATION LA English DT Biographical-Item C1 [Ichinose, Fumito; Zapol, Warren M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM fichinose@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 2045-8932 EI 2045-8940 J9 PULM CIRC JI Pulm. Circ. PD MAR PY 2015 VL 5 IS 1 BP 217 EP 218 DI 10.1086/680856 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA DJ2RM UT WOS:000374052800020 ER PT J AU Thoma, B Sanders, JL Lin, M Paterson, QS Steeg, J Chan, TM AF Thoma, Brent Sanders, Jason L. Lin, Michelle Paterson, Quinten S. Steeg, Jordon Chan, Teresa M. TI The Social Media Index: Measuring the Impact of Emergency Medicine and Critical Care Websites SO WESTERN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE Online medical education; medical education; social media; impact factor; blogs; podcasts AB Introduction: The number of educational resources created for emergency medicine and critical care (EMCC) that incorporate social media has increased dramatically. With no way to assess their impact or quality, it is challenging for educators to receive scholarly credit and for learners to identify respected resources. The Social Media index (SMi) was developed to help address this. Methods: We used data from social media platforms (Google PageRanks, Alexa Ranks, Facebook Likes, Twitter Followers, and Google+ Followers) for EMCC blogs and podcasts to derive three normalized (ordinal, logarithmic, and raw) formulas. The most statistically robust formula was assessed for 1) temporal stability using repeated measures and website age, and 2) correlation with impact by applying it to EMCC journals and measuring the correlation with known journal impact metrics. Results: The logarithmic version of the SMi containing four metrics was the most statistically robust. It correlated significantly with website age (Spearman r=0.372; p<0.001) and repeated measures through seven months (r=0.929; p<0.001). When applied to EMCC journals, it correlated significantly with all impact metrics except number of articles published. The strongest correlations were seen with the Immediacy Index (r=0.609; p<0.001) and Article Influence Score (r=0.608; p<0.001). Conclusion: The SMi's temporal stability and correlation with journal impact factors suggests that it may be a stable indicator of impact for medical education websites. Further study is needed to determine whether impact correlates with quality and how learners and educators can best utilize this tool. C1 [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Learning Lab, Boston, MA 02114 USA. [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Boston, MA 02114 USA. [Thoma, Brent] Univ Saskatchewan, Emergency Med, Saskatoon, SK, Canada. [Thoma, Brent; Sanders, Jason L.; Lin, Michelle; Chan, Teresa M.] MedEdLIFE Res Collaborat, San Francisco, CA USA. [Sanders, Jason L.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Sanders, Jason L.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Lin, Michelle] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Paterson, Quinten S.; Steeg, Jordon] Univ Saskatchewan, Coll Med, Saskatoon, SK S7N 0W0, Canada. [Chan, Teresa M.] McMaster Univ, Dept Med, Div Emergency Med, Hamilton, ON, Canada. RP Thoma, B (reprint author), Royal Univ Hosp, Emergency Med, Room 2686,103 Hosp Dr, Saskatoon, SK S7N 0W8, Canada. EM brent.thoma@usask.ca OI Chan, Teresa/0000-0001-6104-462X; Thoma, Brent/0000-0003-1124-5786 NR 25 TC 10 Z9 10 U1 0 U2 2 PU WESTJEM PI ORANGE PA C/O SHAHRAM LOTFIPOUR, MD, MPH, 333 CITY BLVD W STE 640, RT 128-01, ORANGE, CA 92868 USA SN 1936-900X EI 1936-9018 J9 WEST J EMERG MED JI West. J. Emerg. Med. PD MAR PY 2015 VL 16 IS 2 BP 242 EP 249 DI 10.5811/westjem.2015.1.24860 PG 8 WC Emergency Medicine SC Emergency Medicine GA DH9JQ UT WOS:000373112800006 PM 25834664 ER PT J AU Enggasser, JL Hermos, JA Rubin, A Lachowicz, M Rybin, D Brief, DJ Roy, M Helmuth, E Rosenbloom, D Keane, TM AF Enggasser, Justin L. Hermos, John A. Rubin, Amy Lachowicz, Mark Rybin, Denis Brief, Deborah J. Roy, Monica Helmuth, Eric Rosenbloom, David Keane, Terence M. TI Drinking goal choice and outcomes in a Web-based alcohol intervention: Results from VetChange SO ADDICTIVE BEHAVIORS LA English DT Article DE Alcohol; Veterans; Web intervention; Internet; Drinking goal; Outcomes ID RANDOMIZED CONTROLLED-TRIAL; DISORDERS IDENTIFICATION TEST; REDUCING HEAVY DRINKING; PROBLEM DRINKERS; COLLEGE-STUDENTS; INITIAL PREFERENCE; CLINICAL-TRIAL; SELF-HELP; ABSTINENCE; COMMITMENT AB Objectives: The objectives of the paper are to describe characteristics of participants who chose moderation and abstinence drinking goals, and to examine post-treatment drinking outcomes based on patterns of goal choice during a Web-based alcohol intervention for returning U.S. Veterans. Method: We conducted a descriptive secondary analysis of a subsample of 305 of 600 Veterans who participated in a clinical trial of VetChange, an 8-module, cognitive-behavioural intervention. Participants self-selected abstinence or moderation drinking goals, initially at Module 3, and weekly during subsequent modules. Alcohol use and alcohol-related problems were measured using the Alcohol Use Disorders Identification Test (AUDIT), Quick Drink Screen (Q)S), and Short Inventory of Problems (SIP-2R). Results: Initial goal choices were 86.9% moderation and 13.1% abstinence. Approximately 20% of participants from each initial choice changed goals during the intervention; last goal choices were 68.6% moderation and 31.4% abstinence. Participants who initially chose moderation reported higher percent heavy drinking days at baseline; participants who initially chose abstinence were more likely to report recent substance abuse treatment and were older. Post-intervention levels of alcohol use and alcohol-related problems were significantly reduced in all goal-choice patterns (i.e., Moderation Only, Abstinence Only, Moderation to Abstinence, and Abstinence to Moderation; all measures p < 0.05 or less). Baseline drinking severity did not differentially relate to outcomes across goal-choice patterns. Conclusions: Participants in a Web-based alcohol intervention for returning U.S. Veterans demonstrated improvements in drinking regardless of whether they chose an abstinence or moderation drinking goal, and whether the goal was maintained or changed over the course of the intervention. Published by Elsevier Ltd. C1 [Enggasser, Justin L.; Hermos, John A.; Rubin, Amy; Brief, Deborah J.; Roy, Monica; Keane, Terence M.] VA Boston Healthcare Syst, Boston, MA USA. [Enggasser, Justin L.; Rubin, Amy; Lachowicz, Mark; Brief, Deborah J.; Roy, Monica; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Hermos, John A.; Rubin, Amy] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Rubin, Amy; Lachowicz, Mark; Brief, Deborah J.; Helmuth, Eric; Rosenbloom, David; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Rybin, Denis] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Helmuth, Eric; Rosenbloom, David] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Enggasser, JL (reprint author), VA Boston Healthcare Syst 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM Justin.Enggasser@va.gov OI Rybin, Denis/0000-0002-3657-4829 FU National Institute on Alcohol Abuse and Alcoholism [RC1AA019248] FX This research was supported by Grant RC1AA019248 (Principal Investigator: Terence M. Keane) from the National Institute on Alcohol Abuse and Alcoholism. Aside from the grant review process, NIAAA had no role in the study design, collection, analysis or interpretation of the data, writing this report, or in the decision to submit this report for publication. The contents of this report do not represent the views of the Department of Veterans Affairs or the United States Government. NR 49 TC 4 Z9 4 U1 4 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD MAR PY 2015 VL 42 BP 63 EP 68 DI 10.1016/j.addbeh.2014.10.036 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AZ9SI UT WOS:000348555100012 PM 25671224 ER PT J AU Ditre, JW Langdon, KJ Kosiba, JD Zale, EL Zvolensky, MJ AF Ditre, Joseph W. Langdon, Kirsten J. Kosiba, Jesse D. Zale, Emily L. Zvolensky, Michael J. TI Relations between pain-related anxiety, tobacco dependence, and barriers to quitting among a community-based sample of daily smokers SO ADDICTIVE BEHAVIORS LA English DT Article DE Pain; Smoking; Anxiety; Cessation; Tobacco; Pain-related anxiety ID SMOKING OUTCOME EXPECTANCIES; WISCONSIN INVENTORY; MOTIVES; SENSITIVITY; CESSATION; FEAR; ASSOCIATIONS; DISABILITY; PREDICTION; MOTIVATION AB There is increasing recognition that complex and potentially bidirectional relations between pain and smoking may be relevant to the maintenance of tobacco addiction. Pain-related anxiety has been identified as a mechanism in the onset and progression of painful disorders, and initial evidence indicates that pain-related anxiety may be associated with essential features of tobacco dependence among smokers with chronic pain. However, there has not been an empirical study of pain-related anxiety in relation to tobacco dependence and self-reported barriers to quitting among a community-based sample of daily smokers. The current sample was comprised of 122 daily smokers who were recruited from the local community to participate in a larger study that included an initial assessment of pain, smoking history, and pain-related anxiety. Approximately 17% of our sample endorsed moderate or severe past-month pain, nearly half met criteria for current anxiety or mood disorder, and about 30% met criteria for a current substance use disorder, exclusive of tobacco dependence. Results indicated that pain-related anxiety was uniquely and positively associated with both tobacco dependence severity scores and self-reported barriers to quitting. These findings lend support to the notion that pain-related anxiety may contribute to the maintenance of tobacco addiction among smokers who experience varying levels of pain severity. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Ditre, Joseph W.; Kosiba, Jesse D.; Zale, Emily L.] Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. [Langdon, Kirsten J.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Langdon, Kirsten J.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Zvolensky, Michael J.] Univ Houston, Dept Psychol, Houston, TX 77004 USA. RP Ditre, JW (reprint author), Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. EM jwditre@syr.edu FU NIDA [F31DA026634, R21DA034285] FX Support for the study and preparation of the manuscript was provided by F31DA026634 awarded to Kirsten Johnson, and R21DA034285 awarded to Joseph Ditre by NIDA. NIDA had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. NR 42 TC 4 Z9 4 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD MAR PY 2015 VL 42 BP 130 EP 135 DI 10.1016/Laddbeh.2014.11.032 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AZ9SI UT WOS:000348555100024 PM 25462660 ER PT J AU McLaughlin, NCR Strong, D Abrantes, A Garnaat, S Cerny, A O'Connell, C Fadok, R Spofford, C Rasmussen, SA Milad, MR Greenberg, BD AF McLaughlin, N. C. R. Strong, D. Abrantes, A. Garnaat, S. Cerny, A. O'Connell, C. Fadok, R. Spofford, C. Rasmussen, S. A. Milad, M. R. Greenberg, B. D. TI Extinction retention and fear renewal in a lifetime obsessive-compulsive disorder sample SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Anxiety/anxiety disorders; OCD/obsessive-compulsive disorder; CBT/cognitive behavior therapy; Biological markers; Cognition ID CONDITIONED FEAR AB Obsessive-compulsive disorder (OCD), like other illnesses with prominent anxiety, may involve abnormal fear regulation and consolidation of safety memories. Impaired fear extinction memory (extinction recall, ER) has been shown in individuals with current symptoms of OCD [1]. However, contrary to expectations, the only previous study investigating this phenomenon showed a positive correlation between extinction recall abilities and OCD symptomology (i.e., as OCD symptoms worsened, extinction memory improved). The purpose of the current study was to determine if patients with a lifetime diagnosis of OCD (not necessarily currently symptomatic) also demonstrate impairments in extinction memory, and the relationship between OCD symptomology and extinction memory in this type of sample. In addition, we also examined fear renewal, which has never been investigated in an OCD sample. We enrolled 37 patients with OCD, the majority of whom were on serotonin reuptake inhibitors, and 18 healthy control participants in a 2-day paradigm assessing fear conditioning and extinction (Day 1) and extinction retention and renewal (Day 2). Skin conductance responses (SCRs) were the dependent measure. Results, as in the prior study, indicated that the only between-group difference was impaired ER in OCD patients relative to controls. Contrary to our prediction, OCD symptom severity was not correlated with the magnitude of extinction recall. There were no differences in fear renewal between OCD patients and controls. (C) 2014 Elsevier B.V. All rights reserved. C1 [McLaughlin, N. C. R.; Abrantes, A.; Garnaat, S.; Rasmussen, S. A.; Greenberg, B. D.] Brown Univ, Alpert Med Sch, Butler Hosp, Providence, RI 02912 USA. [Strong, D.] Univ Calif San Diego, San Diego, CA 92103 USA. [Cerny, A.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [O'Connell, C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Fadok, R.] MIT, Cambridge, MA 02139 USA. [Spofford, C.] Providence Vet Affairs Med Ctr, Providence, RI USA. [Milad, M. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP McLaughlin, NCR (reprint author), Butler Hosp, OCD Res Clin, 345 Blackstone Blvd, Providence, RI 02906 USA. FU NIH [MH086400] FX This research was supported by NIH grant MH086400 and funding from a private donor to Butler Hospital's OCD Clinic. The authors would like to thank Melissa Warstadt and Jason Kirschner for their help with data collection. NR 13 TC 7 Z9 7 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAR 1 PY 2015 VL 280 BP 72 EP 77 DI 10.1016/j.bbr.2014.11.011 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AZ5IQ UT WOS:000348255400009 PM 25446749 ER PT J AU Miyahira, AK Kissick, HT Bishop, JL Takeda, DY Barbieri, CE Simons, JW Pienta, KJ Soule, HR AF Miyahira, Andrea K. Kissick, Haydn T. Bishop, Jennifer L. Takeda, David Y. Barbieri, Christopher E. Simons, Jonathan W. Pienta, Kenneth J. Soule, Howard R. TI Beyond Immune Checkpoint Blockade: New Approaches to Targeting Host-Tumor Interactions in Prostate Cancer: Report From the 2014 Coffey-Holden Prostate Cancer Academy Meeting SO PROSTATE LA English DT Article DE prostate cancer; immunotherapy; tumor microenvironment; therapeutics; immunosuppression ID ANTITUMOR IMMUNITY; ANDROGEN RECEPTOR; SURVIVAL ANALYSIS; IMMUNOTHERAPY; CELLS; IPILIMUMAB; MELANOMA; MICROENVIRONMENT; ENZALUTAMIDE; TESTOSTERONE AB INTRODUCTIONThe 2014 Coffey-Holden Prostate Cancer Academy Meeting, held in La Jolla, CA from June 26 to 29, 2014, was themed: Beyond Immune Checkpoint Blockade: New Approaches to Targeting Host-Tumor Interactions in Prostate Cancer. METHODSSponsored by the Prostate Cancer Foundation (PCF), this annual, invitation-only meeting is structured as an action-tank, and brought together 72 investigators with diverse academic backgrounds to discuss the most relevant topics in the fields of prostate cancer immunotherapy and the tumor microenvironment. RESULTSThe questions addressed at the meeting included: mechanisms underlying the successes and failures of prostate cancer immunotherapies, how to trigger an effective immune response against prostate cancer, the tumor microenvironment and its role in therapy resistance and tumor metastasis, clinically relevant prostate cancer mouse models, how host-tumor interactions affect current therapies and tumor phenotypes, application of principles of precision medicine to prostate cancer immunotherapy, optimizing immunotherapy clinical trial design, and complex multi-system interactions that affect prostate cancer and immune responses including the effects of obesity and the potential role of the host microbiome. DISCUSSIONThis article highlights the most significant recent progress and unmet needs that were discussed at the meeting toward the goal of speeding the development of optimal immunotherapies for the treatment of prostate cancer. Prostate 75:337-347, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Miyahira, Andrea K.; Simons, Jonathan W.; Soule, Howard R.] Prostate Canc Fdn, Santa Monica, CA 90401 USA. [Kissick, Haydn T.] Emory Univ, Atlanta, GA 30322 USA. [Bishop, Jennifer L.] Vancouver Prostate Ctr, Vancouver, BC, Canada. [Takeda, David Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Barbieri, Christopher E.] Weill Cornell Med Coll, New York, NY USA. [Pienta, Kenneth J.] James Buchanan Brady Urol Inst, Dept Urol, Baltimore, MD USA. [Pienta, Kenneth J.] Sch Med, Dept Oncol, Baltimore, MD USA. [Pienta, Kenneth J.] Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD USA. RP Soule, HR (reprint author), Prostate Canc Fdn, 1250 4th St, Santa Monica, CA 90401 USA. EM hsoule@pcf.org RI Pienta, Kenneth/E-7679-2015; OI Pienta, Kenneth/0000-0002-4138-2186; Barbieri, Christopher/0000-0002-0381-1947 NR 53 TC 5 Z9 5 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD MAR 1 PY 2015 VL 75 IS 4 BP 337 EP 347 DI 10.1002/pros.22920 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA AY8OA UT WOS:000347811800001 PM 25358693 ER PT J AU Zhou, CK Littman, AJ Levine, PH Hoffman, HJ Cleary, SD White, E Cook, MB AF Zhou, Cindy Ke Littman, Alyson J. Levine, Paul H. Hoffman, Heather J. Cleary, Sean D. White, Emily Cook, Michael B. TI Male Pattern Baldness in Relation to Prostate Cancer Risks: An Analysis in the VITamins and Lifestyle (VITAL) Cohort Study SO PROSTATE LA English DT Article DE male pattern baldness; prostate cancer; androgen; cohort study ID ENDOGENOUS SEX-HORMONES; EARLY-ONSET BALDNESS; ANDROGENETIC ALOPECIA; SERUM TESTOSTERONE; HAIR LOSS; MEN; METAANALYSIS; POLYMORPHISMS; EPIDEMIOLOGY; FINASTERIDE AB BACKGROUNDMale pattern baldness and prostate cancer may share common pathophysiological mechanisms in terms of advancing age, heritability, and endogenous hormones. Results from previous epidemiologic studies are inconsistent. Therefore, we investigated the association of prostate cancer risks with male pattern baldness at age 30 years, age 45 years, and baseline (median age=60.5 years) in the VITamins And Lifestyle (VITAL) cohort study. METHODSWe included 32,583 men who were aged 50-76 years and without prior cancer diagnosis (excluding non-melanoma skin cancer) at the start of follow-up. First primary incident prostate cancers were ascertained via linkage to the western Washington Surveillance, Epidemiology, and End Results (SEER) program. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards regressions with adjustment for potential confounders. RESULTSDuring follow-up (median=9 years), 2,306 incident prostate cancers were diagnosed. Male pattern baldness at age 30 years, age 45 years, and baseline were not statistically significantly associated with overall or subtypes of prostate cancer. CONCLUSIONThis study did not provide support for the hypothesis that male pattern baldness may be a marker for subsequent prostate cancer. Previous evidence indicates that a distinct class of frontal with vertex balding may be associated with increased risk of aggressive prostate cancer, but all such balding classes were captured as a single exposure category by the VITAL cohort questionnaire. Prostate 75:415-423, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Zhou, Cindy Ke; Cook, Michael B.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Zhou, Cindy Ke; Levine, Paul H.; Hoffman, Heather J.; Cleary, Sean D.] George Washington Univ, Dept Epidemiol & Biostat, Washington, DC USA. [Littman, Alyson J.; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Littman, Alyson J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. RP Cook, MB (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 7-E106,MSC 9774, Bethesda, MD 20892 USA. EM michael.cook@nih.gov RI Zhou, Cindy /H-2165-2015; Cook, Michael/A-5641-2009 OI Zhou, Cindy /0000-0003-4814-4305; Cook, Michael/0000-0002-0533-7302 FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health FX Grant sponsor: Intramural Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. NR 50 TC 3 Z9 3 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD MAR 1 PY 2015 VL 75 IS 4 BP 415 EP 423 DI 10.1002/pros.22927 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA AY8OA UT WOS:000347811800008 PM 25492530 ER EF