FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wiener, L Viola, A Koretski, J Perper, ED Patenaude, AF AF Wiener, Lori Viola, Adrienne Koretski, Julia Perper, Emily Diana Patenaude, Andrea Farkas TI Pediatric psycho-oncology care: standards, guidelines, and consensus reports SO PSYCHO-ONCOLOGY LA English DT Article DE pediatric; psychosocial; standards; guidelines; consensus reports ID SIOP WORKING COMMITTEE; QUALITY CANCER CARE; CHILDHOOD-CANCER; ISSUES; CHILDREN; ADOLESCENT; DIAGNOSIS; SURVIVORS; SUPPORT; ASSISTANCE AB ObjectiveThe aim of this study was to identify existing guidelines, standards, or consensus-based reports for psychosocial care of children with cancer and their families. PurposePsychosocial standards of care for children with cancer can systematize the approach to care and create a replicable model that can be utilized in pediatric hospitals around the world. Determining gaps in existing standards in pediatric psycho-oncology can guide development of useful evidence-based and consensus-based standards. MethodsThe MEDLINE and PubMed databases were searched by investigators at two major pediatric oncology centers for existing guidelines, consensus-based reports, or standards for psychosocial care of patients with pediatric cancer and their families published in peer-reviewed journals in English between 1980 and 2013. ResultsWe located 27 articles about psychosocial care that met inclusion criteria: 5 set forth standards, 19 were guidelines, and 3 were consensus-based reports. None was sufficiently up to date, comprehensive, specific enough, or evidence- or consensus-based to serve as a current standard for psychosocial care for children with cancer and their families. ConclusionDespite calls by a number of international pediatric oncology and psycho-oncology professional organizations about the urgency of addressing the psychosocial needs of the child with cancer to reduce suffering, there remains a need for development of a widely acceptable, evidence-based and consensus-based, comprehensive standard of care to guide provision of essential psychosocial services to all patients with pediatric cancer. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. C1 [Wiener, Lori] NCI, NIH, Bethesda, MD 20892 USA. [Viola, Adrienne] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Koretski, Julia; Patenaude, Andrea Farkas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Perper, Emily Diana] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Patenaude, Andrea Farkas] Childrens Hosp, Boston, MA 02115 USA. [Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wiener, L (reprint author), NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 47 TC 7 Z9 7 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2015 VL 24 IS 2 BP 204 EP 211 DI 10.1002/pon.3589 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CA2TN UT WOS:000348760800012 PM 24906202 ER PT J AU Shinagare, AB Ip, IK Lacson, R Ramaiya, NH George, S Khorasani, R AF Shinagare, Atul B. Ip, Ivan K. Lacson, Ronilda Ramaiya, Nikhil H. George, Suzanne Khorasani, Ramin TI Gastrointestinal Stromal Tumor: Optimizing the Use of Cross-sectional Chest Imaging during Follow-up SO RADIOLOGY LA English DT Article ID FEATURES; METASTASIS; SURVIVAL AB Purpose: To identify the frequency of and variables associated with thoracic metastasis in patients with gastrointestinal stromal tumor (GIST) to help optimize the use of cross-sectional chest imaging. Materials and Methods: This retrospective institutional review board-approved study included 631 patients (343 men; mean age, 55 years; range, 19-94 years) with pathologically confirmed GIST who were identified with a natural language processing algorithm in a review of radiologic reports from January 2004 through October 2012, followed by manual confirmation. The requirement for informed consent was waived. Available imaging, pathologic, and clinical records were reviewed to confirm the presence of abdominal and thoracic metastases. The association of age; sex; size, location, mitotic count, and risk stratification of the primary tumor; initial treatment; presence of abdominal metastases; and bulky abdominal metastases (more than 10 lesions larger than 1 cm, or more than five lesions with at least one larger than 5 cm) with development of thoracic metastases, the primary outcome measure, was studied by using logistic regression. Results: During median follow-up of 61.4 months (interquartile range, 37.8-93 months), 401 of 631 (63.5%) patients developed metastatic disease (median interval, 6.9 months; interquartile range, 0-25.6 months), all with peritoneal (n = 324) and/or hepatic metastases (n = 303). Bulky abdominal metastases were found in 218 (34.5%) patients. Although 579 (91.8%) patients underwent chest imaging, only 64 of 631 (10.1%) developed thoracic metastases (median, 51.4 months; interquartile range, 36-78.7 months); all had bulky abdominal metastases except one patient who presented with symptomatic scapular metastasis. Only bulky abdominal metastasis was significantly associated with the development of thoracic metastasis (P < .0001; odds ratio, 42.6; range, 8.6-211.5). Conclusion: Thoracic metastases are relatively uncommon in patients with GIST and are significantly associated only with presence of bulky abdominal metastases. (C) RSNA, 2014 C1 [Shinagare, Atul B.; Ip, Ivan K.; Lacson, Ronilda; Khorasani, Ramin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Shinagare, Atul B.; Ip, Ivan K.; Lacson, Ronilda; Khorasani, Ramin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Evidence Based Imaging, Boston, MA 02115 USA. [Shinagare, Atul B.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [George, Suzanne] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM ashinagare@partners.org NR 24 TC 4 Z9 4 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 FEB PY 2015 VL 274 IS 2 BP 395 EP 404 DI 10.1148/radiol.14132456 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CA1WS UT WOS:000348700300011 PM 25203129 ER PT J AU Honda, JR Wallace, RJ Chan, ED AF Honda, Jennifer R. Wallace, Richard J., Jr. Chan, Edward D. TI First you have to row a little boat SO RESPIROLOGY LA English DT Editorial Material DE infection and inflammation; pneumonia; respiratory infection (non-tuberculous) ID COMPLEX LUNG-DISEASE; NONTUBERCULOUS MYCOBACTERIAL DISEASES; AVIUM-INTRACELLULARE; ETHAMBUTOL; RIFAMPICIN; MACROLIDE; THERAPY C1 [Honda, Jennifer R.; Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. [Honda, Jennifer R.; Chan, Edward D.] Natl Jewish Hlth, Dept Med & Acad Affairs, Denver, CO USA. [Honda, Jennifer R.; Chan, Edward D.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Wallace, Richard J., Jr.] Univ Texas Hlth Sci Ctr Tyler, Dept Med, Tyler, TX USA. [Wallace, Richard J., Jr.] Univ Texas Hlth Sci Ctr Tyler, Mycobacteria Nocardia Res Lab, Tyler, TX USA. RP Honda, JR (reprint author), Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. NR 15 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 EI 1440-1843 J9 RESPIROLOGY JI Respirology PD FEB PY 2015 VL 20 IS 2 BP 181 EP 182 DI 10.1111/resp.12465 PG 2 WC Respiratory System SC Respiratory System GA AZ3EK UT WOS:000348110300003 PM 25581353 ER PT J AU Liu, QY Hu, YJ Yu, HH Yuan, L Hu, J Atik, A Guan, M Li, DL Li, X Tang, SB AF Liu, Qingyun Hu, Yijun Yu, Honghua Yuan, Ling Hu, Jie Atik, Alp Guan, Meng Li, Dongli Li, Xin Tang, Shibo TI COMPARISON OF INTRAVITREAL TRIAMCINOLONE ACETONIDE VERSUS INTRAVITREAL BEVACIZUMAB AS THE PRIMARY TREATMENT OF CLINICALLY SIGNIFICANT MACULAR EDEMA SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE CSME; DME; bevacizumab; triamcinolone acitonide; OCT ID OPTICAL COHERENCE TOMOGRAPHY; DIABETIC-RETINOPATHY; AQUEOUS-HUMOR; INJECTION; PATTERNS; EFFICACY; THERAPY AB Objectives: To evaluate the short-term efficacy of triamcinolone acetonide versus bevacizumab for the treatment of diabetic, clinically significant, macular edema with different optical coherence tomography findings. Methods: Fifty eyes of 45 consecutive patients with diabetic, clinically significant, macular edema were incorporated in this prospective interventional case series. Patients were divided into 3 groups according to findings on optical coherence tomography: 1) macular edema combined with serous retinal detachment (Group 1), 2) diffused macular thickening (Group 2), and 3) cystoid macular edema (Group 3). Patients from each group were treated with a single intravitreal injection of triamcinolone (IVTA) or 2 intravitreal injections of bevacizumab (IVB) with an interval of 6 weeks. Patients were observed at 6, 12, and 24 weeks after IVTA or the first IVB injection. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were examined at each visit. Repeated-measures analysis of variance was used to compare the efficacy of the treatment groups. Results: In Group 1, IVTA showed more favorable effects on CRT reduction and BCVA improvement compared with IVB at 6, 12, and 24 weeks (P = 0.002, 0.001, 0.027 and P = 0.036, 0.001, 0.027), respectively. In Group 2, IVB had more CRT reduction than IVTA at 6 and 12 weeks (P = 0.013 and 0.036), although there was no significant difference in BCVA improvement between the 2 groups (p > 0.05). In Group 3, IVTA and IVB did not have significant effects on CRT reduction and BCVA improvement (p > 0.05). Conclusion: The short-term efficacy of IVTA and IVB on treating clinically significant macular edema varied with different optical coherence tomography findings. In clinically significant macular edema combined with serous retinal detachment, IVTA may be more favorable than IVB in CRT reduction and BCVA improvement. In patients with diffused macular thickening, IVB may be better than IVTA in macular thickness reduction, although this does not translate to a significant improvement in BCVA. C1 [Liu, Qingyun] Tongliao City Hosp, Dept Ophthalmol, Tongliao, Peoples R China. [Hu, Yijun; Hu, Jie] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China. [Hu, Yijun; Atik, Alp] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Yu, Honghua] Gen Hosp Guangzhou Mil Command PLA, Dept Ophthalmol, Guangzhou, Guangdong, Peoples R China. [Yuan, Ling; Guan, Meng; Li, Dongli] Kunming Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Kunming, Peoples R China. [Tang, Shibo] Cent S Univ, Aier Sch Ophthalmol, Changsha 410015, Hunan, Peoples R China. RP Tang, SB (reprint author), Cent S Univ, Aier Sch Ophthalmol, Fourth Floor,198 Middle Furong Rd, Changsha 410015, Hunan, Peoples R China. EM tangshibo@vip.163.com FU National Natural Science Foundation of China [81260151]; Applied Basic Research Foundation of the Department of Science and Technology of Yunnan Province [2011FB062]; Science and Technology Foundation of the Department of Health of Yunnan Province [2011WS0041] FX Supported by grant 81260151 from the National Natural Science Foundation of China (L. Yuan), grant 2011FB062 from the Applied Basic Research Foundation of the Department of Science and Technology of Yunnan Province (L. Yuan), and grant 2011WS0041 from the Science and Technology Foundation of the Department of Health of Yunnan Province (L. Yuan). NR 30 TC 4 Z9 4 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD FEB PY 2015 VL 35 IS 2 BP 272 EP 279 PG 8 WC Ophthalmology SC Ophthalmology GA CA2UU UT WOS:000348764200016 PM 25105313 ER PT J AU Abou Zahr, Z Spiegelman, A Cantu, M Ng, B AF Abou Zahr, Zaki Spiegelman, Andrew Cantu, Maria Ng, Bernard TI Perioperative use of anti-rheumatic agents does not increase early postoperative infection risks: a Veteran Affairs' administrative database study SO RHEUMATOLOGY INTERNATIONAL LA English DT Article DE Anti-TNF drugs; Rheumatoid arthritis; Disease-modifying anti-rheumatic drugs (DMARD); Infection; Surgery ID RHEUMATOID-ARTHRITIS PATIENTS; FACTOR-ALPHA BLOCKERS; NECROSIS-FACTOR; METHOTREXATE; COMPLICATIONS; SURGERY; DRUGS; HAND AB The aim of this study was to validate a novel technique that predicts stopping of disease-modifying anti-rheumatic drugs (DMARDs) and biologic agents (BA) from the Veterans Affairs (VA) database and compare infection risks of rheumatoid arthritis patients who stopped versus continued DMARDs/BA perioperatively. We identified 6,024 patients on 1 DMARD or BA in the perioperative period between 1999 and 2009. Time gap between medication stop date and the next start date predicted drug stoppage (X). Time gap between surgery date and stop date predicted whether stoppage was before surgery (Y). Chart review from Houston VA was used for validation. ROC analyses were performed on chart review data to obtain X and Y cutoffs. The primary endpoints were wound infections and other infections within 30 days. ROC analyses found X a parts per thousand yen 33 (AUC = 0.954) and Y a parts per thousand yen -11 (AUC = 0.846). Risk of postoperative infections was not different when stopping and continuing DMARDs/BA preoperatively. Stopping BA after surgery was associated with higher odds of postoperative wound (OR 14.15, 95 % CI 1.76-113.76) and general infection (OR 9.2, 95 % CI 1.99-42.60) compared to not stopping. Stopping DMARDs after surgery was associated with increased risk of postoperative general infection (OR 1.84, 95 % CI 1.07-3.16) compared with not stopping. There was positive association between stopping DMARDs after surgery and postoperative wound infection but failed to achieve statistical significance (OR 1.67, 95 % CI 0.96-2.91). There was no significant difference in postoperative infection risk when stopping or continuing DMARD/BA. Our new validated method can be utilized in the VA and other databases to predict drug stoppage. C1 [Abou Zahr, Zaki] Univ Minnesota, Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Spiegelman, Andrew] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Cantu, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Ng, Bernard] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Ng, B (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM dr_zaki_abouzahr@yahoo.com; bernardng1@gmail.com FU Department of Veteran Affairs, Veterans Health Administration, Health Services Research and Development Service [VA.SCV.1010./000-00.B_N]; Veterans Affairs Health Services Research and Development Service Houston Center of Excellence [HFP90-020]; South Central VA Health Care Network Research Pilot Grant Award FX The research reported here was supported by the Department of Veteran Affairs, Veterans Health Administration, Health Services Research and Development Service, (VA.SCV.1010./000-00.B_N). This work was also partly supported by the Veterans Affairs Health Services Research and Development Service Houston Center of Excellence (HFP90-020). Dr. Bernard Ng held a South Central VA Health Care Network Research Pilot Grant Award and was a consultant to UCB Pharmaceuticals. The rest of the authors have no conflicts of interest to declare. The funding sources had no role in the study design, conduct and analysis or in the decision to submit the manuscript for publication. NR 25 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0172-8172 EI 1437-160X J9 RHEUMATOL INT JI Rheumatol. Int. PD FEB PY 2015 VL 35 IS 2 BP 265 EP 272 DI 10.1007/s00296-014-3121-0 PG 8 WC Rheumatology SC Rheumatology GA CA5YB UT WOS:000348983300006 PM 25187198 ER PT J AU Hazlett, EA Rothstein, EG Ferreira, R Silverman, JM Siever, LJ Olincy, A AF Hazlett, Erin A. Rothstein, Ethan G. Ferreira, Rui Silverman, Jeremy M. Siever, Larry J. Olincy, Ann TI Sensory gating disturbances in the spectrum: Similarities and differences in schizotypal personality disorder and schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizotypal personality disorder; Schizophrenia; Event-related potential; Evoked potential; P50; Psychophysiology; Sensory gating ID REPEATED AUDITORY-STIMULI; DEFICIENT ATTENTIONAL MODULATION; P50 SUPPRESSION; BIPOLAR DISORDER; EVOKED-RESPONSE; POTENTIAL ABNORMALITIES; COGNITIVE IMPAIRMENT; NICOTINIC RECEPTORS; STARTLE RESPONSE; WORKING-MEMORY AB Background: DSM-5 places schizophrenia on a continuum from severe, chronic schizophrenia to the attenuated schizophrenia-like traits of schizotypal personality disorder (SPD), the prototypic schizophrenia-related personality disorder. SPD shares common genetic and neurobiological substrates with schizophrenia, including information processing abnormalities, although they are less marked. This is the first study to directly compare the P50 evoked electroencephalographic response-a measure of sensory gating and a neurophysiological endophenotype-between schizophrenia-spectrum groups. Two hypotheses were tested: (1) Compared with healthy controls (HCs), schizophrenia patients show reduced P50 suppression and SPD patients resemble schizophrenia but exhibit less marked deficits; and (2) Deficient P50 suppression in SPD is associated with greater clinical symptom severity. Methods: P50 was assessed in 32 schizophrenia-spectrum disorder patients (12 SPD, 20 schizophrenia patients) and 25 demographically-matched HCs. The standard conditioning (C)-testing (T) paradigm was used and P50 suppression was quantified using the T-C difference and the T/C ratio. Results: All P50 measures showed a linear, stepwise pattern with the SPD group intermediate between the HC and schizophrenia groups. Compared with HCs, both patient groups had lower conditioning and T-C difference values. Among the SPD group, greater clinical symptom severity was associated with greater conditioning-response amplitude deficits. Conclusion: These findings: (1) are novel in showing that P50 deficits in SPD resemble those observed in schizophrenia, albeit less marked; (2) support the concept that the phenomenological link between SPD and schizophrenia lies in shared neurocognitive/neurophysiological pathologies; and (3) provide evidence that P50 is a neurophysiological endophenotype for schizophrenia-spectrum disorders. Published by Elsevier B.V. C1 [Hazlett, Erin A.; Rothstein, Ethan G.; Ferreira, Rui; Silverman, Jeremy M.; Siever, Larry J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Hazlett, Erin A.; Silverman, Jeremy M.; Siever, Larry J.] James J Peters VA Med Ctr, Res & Dev, Bronx, NY 10468 USA. [Hazlett, Erin A.; Siever, Larry J.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN3, Bronx, NY 10468 USA. [Olincy, Ann] Univ Colorado, Dept Psychiat, Denver, CO 80202 USA. RP Hazlett, EA (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN3, 130 West Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM erin.hazlett@mssm.edu FU VA MERIT Award [I01CX000261]; NIMH Collaborative R01 grant [R01MH065554, R01MH056140]; National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) [UL1TR000067] FX Support for this work came from a VA MERIT Award I01CX000261 to E. A. H., NIMH Collaborative R01 grants to each of the seven Consortia on Genetics of Schizophrenia (COGS) sites including R01MH065554 to L.J.S, R01MH056140 to L.J.S., and grant no. UL1TR000067 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). NR 87 TC 3 Z9 3 U1 3 U2 9 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 FEB PY 2015 VL 161 IS 2-3 BP 283 EP 290 DI 10.1016/j.schres.2014.11.020 PG 8 WC Psychiatry SC Psychiatry GA AZ8GB UT WOS:000348452100021 PM 25482574 ER PT J AU Trockel, M Karlin, BE Taylor, CB Brown, GK Manber, R AF Trockel, Mickey Karlin, Bradley E. Taylor, C. Barr Brown, Gregory K. Manber, Rachel TI Effects of Cognitive Behavioral Therapy for Insomnia on Suicidal Ideation in Veterans SO SLEEP LA English DT Article DE cognitive behavioral therapy; insomnia; suicidal ideation; dissemination; Veterans ID RANDOMIZED CONTROLLED-TRIAL; SLEEP DISTURBANCE; NATIONAL-DISSEMINATION; PERSISTENT INSOMNIA; DEPRESSIVE SYMPTOMS; FOLLOW-UP; ADULTS; SYSTEM; PHARMACOTHERAPY; METAANALYSIS AB Objective: To examine the effects of cognitive behavioral therapy for insomnia (CBT-I) on suicidal ideation among Veterans with insomnia. Design: Longitudinal data collected in the course of an uncontrolled evaluation of a large-scale CBT-I training program. Setting: Outpatient and residential treatment facilities. Participants: Four hundred five Veterans presenting for treatment of insomnia. Interventions: Cognitive behavioral therapy for insomnia. Measurement and Results: At baseline, 32% of patients, compared with 21% at final assessment, endorsed some level of suicidal ideation [chi(2)(df = 1) = 125; P < 0.001]. After adjusting for demographic variables and baseline insomnia severity, each 7-point decrease in Insomnia Severity Index score achieved during CBT-I treatment was associated with a 65% (odds ratio = 0.35; 95% confidence intervals = 0.24 to 0.52) reduction in odds of suicidal ideation. The effect of change in insomnia severity on change in depression severity was also significant. After controlling for change in depression severity and other variables in the model, the effect of change in insomnia severity on change in suicidal ideation remained significant. Conclusion: This evaluation of the largest dissemination of cognitive behavioral therapy for insomnia (CBT-I) in the United States found a clinically meaningful reduction in suicidal ideation among Veterans receiving CBT-I. The mechanisms by which effective treatment of insomnia with CBT-I reduces suicide risk are unknown and warrant investigation. The current results may have significant public health implications for preventing suicide among Veterans. C1 [Trockel, Mickey; Manber, Rachel] Vet Affairs Palo Alto Hlth Care Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Palo Alto, CA USA. [Trockel, Mickey; Taylor, C. Barr; Manber, Rachel] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Karlin, Bradley E.] US Dept Vet Affairs, Cent Off, Mental Hlth Serv, Washington, DC USA. [Karlin, Bradley E.] Educ Dev Ctr Inc, New York, NY 10014 USA. [Karlin, Bradley E.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Brown, Gregory K.] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Brown, Gregory K.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Karlin, BE (reprint author), Educ Dev Ctr Inc, Mental Hlth & Aging, 96 Morton St,7th Floor, New York, NY 10014 USA. EM bradkarlin@gmail.com FU Mental Health Services, U.S. Department of Veterans Affairs Central Office FX This was not an industry supported study. This project was supported by Mental Health Services, U.S. Department of Veterans Affairs Central Office. Dr. Karlin is currently affiliated with the Education Development Center, Inc., and the Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University. Dr. Manber is a co-author of a workbook related to the treatment described in this paper from which she receives royalties. The other authors have indicated no financial conflicts of interest. NR 47 TC 17 Z9 17 U1 1 U2 12 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 FEB 1 PY 2015 VL 38 IS 2 BP 259 EP 265 DI 10.5665/sleep.4410 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CA2SO UT WOS:000348757800014 PM 25515115 ER PT J AU Manconi, M Zavalko, I Fanfulla, F Winkelman, JW Fulda, S AF Manconi, Mauro Zavalko, Irina Fanfulla, Francesco Winkelman, John W. Fulda, Stephany TI An Evidence-Based Recommendation for a New Definition of Respiratory-Related Leg Movements SO SLEEP LA English DT Article DE respiratory-related leg movements; periodic leg movements; sleep apnea ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE AIRWAY PRESSURE; PERIODIC LIMB MOVEMENTS; HEART-FAILURE; PREVALENCE; MORTALITY; WAKEFULNESS; DISORDER; THERAPY; PLMS AB Study Objectives: Current sleep scoring rules exclude leg movements that occur near respiratory events from being scored as periodic leg movements during sleep (PLMS) but differ in whether they exclude leg movements occurring at the end (WASM/IRLSSG) or during a respiratory event (AASM). The aim of the present study was to describe the distribution of leg movements in relation to respiratory events and to contribute to an evidence-based rule for the identification and scoring of respiratory-related leg movements (RRLMs). Design: Retrospective chart review and analysis of polysomnographic recordings. Setting: Clinical sleep laboratory. Participants: 64 patients with polysomnographic recordings between January 2010 and July 2011, aged 18 to 75 years, with AHI > 20, ODI > 10, more than 50% of apneas being obstructive, > 15 leg movements of any type per hour of sleep, no more than 20% of total sleep time with artifacts and no medical condition or medication that could influence leg movements or respiratory disturbances. Interventions: None. Measurements and Results: Back-averaging of leg movement activity (LMA) with respect to respiratory events revealed that LMA was present shortly before the end of the respiratory events, but occurred mostly following respiratory events with peak onset of LMA 2.5 s after respiratory event termination. Increased LMA before the beginning of the respiratory event consisted mainly of the tail of LMA after the end of the previous respiratory event. Change-point analysis indicated that LMA was increased over an interval of -2.0 s to +10.25 s around the end of respiratory events. Changing the definition of RRLMs had a significant influence on PLMS counts. The number of patients with obstructive sleep apnea with PLMS index > 15 was 80% when considering the WASM/IRLSSG definition, 67% for the AASM criteria, and 41% when based on the interval identified by change-point analysis (-2.0 to 10.25 s). Conclusions: Leg movements are not augmented at the beginning or middle of respiratory events but are increased around the end of respiratory events over a period significantly longer than specified in the AASM and the WASM/IRLSSG rules. Both rules underestimate the number of respiratory-related leg movements and thus overestimate the number of periodic leg movements during sleep in patients with obstructive sleep apnea. C1 [Manconi, Mauro; Zavalko, Irina; Fulda, Stephany] Civ Hosp EOC Lugano, Sleep & Epilepsy Ctr, Neuroctr Southern Switzerland, CH-6900 Lugano, Switzerland. [Zavalko, Irina] Russian Acad Sci, Inst Biomed Problems, Moscow, Russia. [Fanfulla, Francesco] Salvatore Maugeri Fdn IRCCS, Sci Inst Pavia, Sleep Ctr, Pavia, Italy. [Winkelman, John W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Sleep Disorders Clin Res Program, Boston, MA USA. RP Fulda, S (reprint author), Civ Hosp EOC Lugano, Sleep & Epilepsy Ctr, Neuroctr Southern Switzerland, Via Tesserete 46, CH-6900 Lugano, Switzerland. EM stephany.fulda@gmail.com OI Fanfulla, Francesco/0000-0002-8601-423X NR 29 TC 10 Z9 10 U1 0 U2 4 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 FEB 1 PY 2015 VL 38 IS 2 BP 295 EP 304 DI 10.5665/sleep.4418 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CA2SO UT WOS:000348757800018 PM 25325500 ER PT J AU Tanabe, KK AF Tanabe, Kenneth K. TI Commentary on "Can we improve the morbidity and mortality associated with the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure in the management of colorectal liver metastases?" SO SURGERY LA English DT Editorial Material ID RESECTION C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ktanabe@partners.org NR 10 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 2015 VL 157 IS 2 BP 204 EP 206 DI 10.1016/j.surg.2014.08.053 PG 3 WC Surgery SC Surgery GA CA5TX UT WOS:000348971800004 PM 25433729 ER PT J AU Valsangkar, NP Ingkakul, T Correa-Gallego, C Mino-Kenudson, M Masia, R Lillemoe, KD Fernandez-del Castillo, C Warshaw, AL Liss, AS Thayer, SP AF Valsangkar, Nakul P. Ingkakul, Thun Correa-Gallego, Camilo Mino-Kenudson, Mari Masia, Ricard Lillemoe, Keith D. Fernandez-del Castillo, Carlos Warshaw, Andrew L. Liss, Andrew S. Thayer, Sarah P. TI Survival in ampullary cancer: Potential role of different KRAS mutations SO SURGERY LA English DT Article ID K-RAS MUTATION; ADJUVANT CHEMORADIATION THERAPY; COLORECTAL-CANCER; PROGNOSTIC VALUE; LUNG ADENOCARCINOMAS; CARCINOMA; VATER; PREDICTORS; PANCREATICODUODENECTOMY; NODES AB Objective. The prognosis of ampullary adenocarcinoma (AA) usually is favorable; however a subset of AA have poor biology and outcomes similar to pancreatic cancer Patients in this subset will have early recurrence and death usually within 2 years. To date, there are no genetic markers to identify these patients. This study identifies the high-risk subset of AA and evaluates the mutational status of KRAS in predicting poor outcome. Methods. The tumor registry of an academic center was reviewed for data on patients managed operatively with AA. KRAS genotypes were determined for these patients using a polymerase chain reaction-based assay on clinical specimens. Analysis of variance and chi(2) tests was used to categorize continuous and categorical variables. Univariate and multivariate survival analyses were performed using Kaplan-Meier and Cox methods, respectively. Results. A total of 146 patients were identified with AA between 1982 and 2008. After stringent pathologic review, 97 patients were confirmed with AA, of whom 75 had tissue specimens available for analysis. Genotyping revealed 67% were wild-type (KRAS(wT)), and 33% were mutant for KRAS. Patients with KRAS(G12D) (n = 9), the most common mutational genotype, had poorer median survival (62 months) compared with those with KRAS(non-G12D) mutants (median survival not reached, mean 145 months) and KRAS(WT) patients (155 months, P = .05). Patients with survival 30 months were labeled "high-risk." Of the 9 patients with KRAS(G12D), 56% were in this high-risk subset, compared with 18% of KRAS(WT) (P = .02) and 31% of KRAS(non-G12D) (P > .05) populations. Patients with KRAS(G12D) also were more likely to present with advanced T stage. Conclusion. The KRAS(G12D) mutation identifies a subset of AA patients with poor prognoses and may be used to identifiy patients at risk of early recurrence and poorer survival who may benefit from adjuvant therapy. C1 [Valsangkar, Nakul P.; Ingkakul, Thun; Correa-Gallego, Camilo; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Liss, Andrew S.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mino-Kenudson, Mari; Masia, Ricard] Massachusetts Gen Hosp, Dept Pathol, MD Inst Pancreat Canc Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Thayer, SP (reprint author), Univ Nebraska Med Ctr, Div Surg Oncol, Fred & Pamela Buffett Canc Ctr, 986345 Nebraska Med Ctr, Omaha, NE 68198 USA. EM sarah.thayer@unmc.edu FU National Cancer Institute [CA117969, GA127003] FX Supported by the Andrew L. Warshaw, M.D. Institute for Pancreatic Cancer Research (to N.P.V.) and the grants CA117969, GA127003 from the National Cancer Institute (to S.P.T.). NR 36 TC 8 Z9 8 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 2015 VL 157 IS 2 BP 260 EP 268 DI 10.1016/j.surg.2014.08.092 PG 9 WC Surgery SC Surgery GA CA5TX UT WOS:000348971800011 PM 25616942 ER PT J AU Stey, AM Russell, MM Ko, CY Sacks, GD Dawes, AJ Gibbons, MM AF Stey, Anne M. Russell, Marcia M. Ko, Clifford Y. Sacks, Greg D. Dawes, Aaron J. Gibbons, Melinda M. TI Clinical registries and quality measurement in surgery: A systematic review SO SURGERY LA English DT Review ID OUTCOMES LONGITUDINAL DATABASE; SURGICAL-SITE-INFECTION; RISK-ADJUSTED OUTCOMES; ARTERY-BYPASS-SURGERY; OF-VETERANS-AFFAIRS; ABDOMINAL AORTIC-ANEURYSM; NORTHERN NEW-ENGLAND; VENA-CAVA FILTERS; TRAUMA DATA-BANK; BARIATRIC-SURGERY AB Background. Surgical clinical registries provide clinical information with the intent of measuring and improving quality. This study aimed to describe how surgical clinical registries have been used to measure surgical quality, the reported findings, and the limitations of registry measurements. Methods. Medline, CINAHL, and Cochrane were queried for English articles with the terms: "registry AND surgery AND quality. "Eligibility criteria were studies explicitly assessing quality measurement with registries as the primary data source. Studies were abstracted to identify registries, define registry structure, uses for quality measurement, and limitations of the measurements used. Results. A total of 111 studies of 18 registries were identified for data abstraction. Two registries were financed privately, and 5 registries were financed by a governmental organization. Across registries, the most common uses of process measures were for monitoring providers and as platforms for quality improvement initiatives. The most common uses of outcome measures were to improve quality modeling and to identify preoperative risk factors for poor outcomes. Eight studies noted improvements in risk-adjusted mortality with registry participation; one found no change. A major limitation is bias from context and means of data collection threatening internal validity of registry quality measurement. Conversely, the other major limitation is the cost of participation, which threatens the external validity of registry quality measurement. Conclusion. Clinical registries have advanced surgical quality definition, measurement, and modeling as well as having served as platforms for local initiatives for quality improvement. The implication of this finding is that subsidizing registry participation may improve data validity as well as engage providers in quality improvement. C1 [Stey, Anne M.] Mt Sinai Med Ctr, Icahn Sch Med, Los Angeles, CA 90024 USA. [Stey, Anne M.; Russell, Marcia M.; Ko, Clifford Y.; Sacks, Greg D.; Dawes, Aaron J.; Gibbons, Melinda M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Russell, Marcia M.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Ko, Clifford Y.] Amer Coll Surg, Chicago, IL USA. RP Stey, AM (reprint author), Mt Sinai Med Ctr, Icahn Sch Med, 10940 Wilshire Blvd,Suite 710, Los Angeles, CA 90024 USA. EM astey@mednet.ucla.edu OI Stey, Anne/0000-0002-8334-0304; Dawes, Aaron/0000-0003-4574-6765 FU Robert Wood Johnson Foundation Clinical Scholars program; U.S. Department of Veterans Affairs [70039] FX A.M.S., A.D., G.D.S. time was supported for this publication by The Robert Wood Johnson Foundation Clinical Scholars program and the U.S. Department of Veterans Affairs Grant number 70039. NR 140 TC 11 Z9 11 U1 3 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 2015 VL 157 IS 2 BP 381 EP 395 DI 10.1016/j.surg.2014.08.097 PG 15 WC Surgery SC Surgery GA CA5TX UT WOS:000348971800025 PM 25616951 ER PT J AU Mehra, S Tuttle, RM Milas, M Orloff, L Bergman, D Bernet, V Brett, E Cobin, R Doherty, G Judson, BL Klopper, J Lee, S Lupo, M Machac, J Mechanick, JI Randolph, G Ross, DS Smallridge, R Terris, D Tufano, R Alon, E Clain, J DosReis, L Scherl, S Urken, ML AF Mehra, Saral Tuttle, R. Michael Milas, Mira Orloff, Lisa Bergman, Donald Bernet, Victor Brett, Elise Cobin, Rhoda Doherty, Gerard Judson, Benjamin L. Klopper, Joshua Lee, Stephanie Lupo, Mark Machac, Josef Mechanick, Jeffrey I. Randolph, Gregory Ross, Douglas S. Smallridge, Robert Terris, David Tufano, Ralph Alon, Eran Clain, Jason DosReis, Laura Scherl, Sophie Urken, Mark L. TI Database and Registry Research in Thyroid Cancer: Striving for a New and Improved National Thyroid Cancer Database SO THYROID LA English DT Review ID PROGNOSTIC SCORING SYSTEM; UNITED-STATES; DATA-BASE; PERIOPERATIVE INFORMATION; RISK-GROUP; CARCINOMA; SURVIVAL; PAPILLARY; WELL; COMMUNICATION AB Background: Health registries have become extremely powerful tools for cancer research. Unfortunately, certain details and the ability to adapt to new information are necessarily limited in current registries, and they cannot address many controversial issues in cancer management. This is of particular concern in differentiated thyroid cancer, which is rapidly increasing in incidence and has many unknowns related to optimal treatment and surveillance recommendations. Summary: In this study, we review different types of health registries used in cancer research in the United States, with a focus on their advantages and disadvantages as related to the study of thyroid cancer. This analysis includes population-based cancer registries, health systems-based cancer registries, and patient-based disease registries. It is important that clinicians understand the way data are collected in, as well as the composition of, these different registries in order to more critically interpret the clinical research that is conducted using that data. In an attempt to address shortcoming of current databases for thyroid cancer, we present the potential of an innovative web-based disease management tool for thyroid cancer called the Thyroid Cancer Care Collaborative (TCCC) to become a patient-based registry that can be used to evaluate and improve the quality of care delivered to patients with thyroid cancer as well as to answer questions that we have not been able to address with current databases and registries. Conclusion: A cancer registry that follows a specific patient, is integrated into physician workflow, and collects data across different treatment sites and different payers does not exist in the current fragmented system of healthcare in the United States. The TCCC offers physicians who treat thyroid cancer numerous time-saving and quality improvement services, and could significantly improve patient care. With rapid adoption across the nation, the TCCC could become a new paradigm for database research in thyroid cancer to improve our understanding of thyroid cancer management. C1 [Mehra, Saral; Judson, Benjamin L.] Yale Univ, Sch Med, Dept Surg Otolaryngol, New Haven, CT 06520 USA. [Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Milas, Mira] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Orloff, Lisa] Stanford Otolaryngol Head & Neck Surg, Stanford, CA USA. [Bergman, Donald; Brett, Elise] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. [Bernet, Victor; Smallridge, Robert] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Cobin, Rhoda] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, Ridgewood, NJ USA. [Doherty, Gerard] Boston Univ, Med Ctr, Dept Surg, Boston, MA USA. [Klopper, Joshua] Univ Colorado Denver, Aurora, CO USA. [Lee, Stephanie] Boston Med Ctr, Dept Med, Sect Endocrinol Diabet & Nutr, Boston, MA USA. [Lupo, Mark] Florida State Univ, Coll Med, Sarasota, FL USA. [Lupo, Mark] Florida State Univ, Thyroid & Endocrine Ctr Florida, Sarasota, FL USA. [Machac, Josef; Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Randolph, Gregory] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Terris, David] Med Coll Georgia, Augusta, GA 30912 USA. [Tufano, Ralph] Johns Hopkins Sch Med, Baltimore, MD USA. [Alon, Eran] Tel Aviv Univ, Sackler Sch Med, Tel Hashomer, Israel. [Clain, Jason; DosReis, Laura; Scherl, Sophie] THANC Fdn, New York, NY USA. [Urken, Mark L.] Mt Sinai Beth Israel Med Ctr, New York, NY USA. RP Mehra, S (reprint author), Yale Univ, Sch Med, 333 Cedar St,Box 208041, New Haven, CT 06520 USA. EM saral.mehra@yale.edu FU Mount Sinai Health System; Thyroid Head and Neck Cancer (THANC) Foundation FX The preparation of this article was supported by a generous grant from the Mount Sinai Health System and the Thyroid Head and Neck Cancer (THANC) Foundation. NR 37 TC 7 Z9 8 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD FEB 1 PY 2015 VL 25 IS 2 BP 157 EP 168 DI 10.1089/thy.2014.0270 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CA6HQ UT WOS:000349012300003 PM 25517683 ER PT J AU Sammon, JD McKay, RR Kim, SP Sood, A Sukumar, S Hayn, MH Hu, JC Kibel, AS Nguyen, PL Peabody, JO Saad, F Sun, M Varda, B Menon, M Choueiri, TK Trinh, QD AF Sammon, Jesse D. McKay, Rana R. Kim, Simon P. Sood, Akshay Sukumar, Shyam Hayn, Matthew H. Hu, Jim C. Kibel, Adam S. Nguyen, Paul L. Peabody, James O. Saad, Fred Sun, Maxine Varda, Briony Menon, Mani Choueiri, Toni K. Quoc-Dien Trinh TI Burden of Hospital Admissions and Utilization of Hospice Care in Metastatic Prostate Cancer Patients SO UROLOGY LA English DT Article ID UNITED-STATES; INCREASED SURVIVAL; ZOLEDRONIC ACID; CHEMOTHERAPY; COST; ABIRATERONE; CARCINOMA; ANTIGEN AB OBJECTIVE To examine the rates of hospitalization in patients with metastatic prostate cancer (mCaP), as well as the effect of hospice utilization on the cost patterns of mCaP. Over the past decade, dramatic changes in the management of advanced prostate cancer have proceeded alongside changes in end-of-life care. But, the impact of these contemporary advances in management of mCaP and its implications on US health care expenditure remains unknown. METHODS Patients hospitalized with mCaP from 1998 to 2010 were extracted from the Nationwide Inpatient Sample (n = 100,220). Temporal trends in incidence and charges were assessed by linear regression. Complex samples logistic regression models were used to identify the predictors of in-hospital mortality, elevated hospital charges beyond the 75th percentile and hospice utilization. RESULTS Between 1998 and 2010, admissions for mCaP decreased at a rate of -5.95% per year (P<.001), whereas per-incident charges increased at the rate of 6.1% (P<.001) annually; the national economic burden of care was stable. Over the study period, hospice use increased 488.0% per year (P<.001) but was significantly lower among black (odds ratio [OR], 0.73; P = .01) and Hispanic (OR, 0.65; P = .03) patients. In multivariable analyses, hospice utilization was associated with decreased odds of elevated hospital charges beyond the 75th percentile (OR, 0.84; P = .02). CONCLUSION Despite a decline in hospitalizations for mCaP, the economic burden of care has remained stable. Increasing use of hospice services has moderated the effect of rising per-incident hospital charges, highlighting the importance of promoting access to hospice in the right clinical setting. These findings have important policy implications, particularly as advances in treatment are expected to further increase expenditures related the inpatient management of mCaP. (C) 2015 Elsevier Inc. C1 Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Yale Univ, Dept Urol, New Haven, CT USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Div Urol Oncol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. Univ Minnesota, Dept Urol, Minneapolis, MN USA. Maine Med Ctr, Dept Urol, Portland, ME 04102 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Montreal, Ctr Hosp, Div Urol, Montreal, PQ, Canada. Univ Montreal, Ctr Hosp, Div Urol, Montreal, PQ, Canada. Univ Montreal, Ctr Hosp, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. RP Trinh, QD (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 45 Francis St,ASB II-3, Boston, MA 02115 USA. EM trinh.qd@gmail.com NR 28 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD FEB PY 2015 VL 85 IS 2 BP 343 EP 349 DI 10.1016/j.urology.2014.09.053 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AZ9UN UT WOS:000348562200020 PM 25623683 ER PT J AU Hshieh, TT Petrone, AB Gaziano, JM Djousse, L AF Hshieh, Tammy T. Petrone, Andrew B. Gaziano, J. Michael Djousse, Luc TI Nut consumption and risk of mortality in the Physicians' Health Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE cardiovascular disease; coronary artery disease; mortality; nut consumption; nuts ID POLYUNSATURATED FATTY-ACIDS; CORONARY-HEART-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; MEDITERRANEAN DIET; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; INFLAMMATORY MARKERS; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; PRIMARY PREVENTION AB Background: Previous studies have suggested that nut consumption is associated with beneficial cardiovascular outcomes. However, limited data are available on the association between nut intake and all-cause mortality. Objective: Our aim was to test the hypothesis that nut consumption is inversely associated with the risk of all-cause mortality. Design: In this prospective cohort study in 20,742 male physicians, we assessed nut intake between 1999 and 2002 via a food-frequency questionnaire and ascertained deaths through an endpoint committee. We used Cox regression to estimate multivariable-adjusted HRs for death according to nut consumption. In secondary analyses, we evaluated associations of nut consumption with cause-specific mortality. Results: During a mean follow-up of 9.6 y, there were 2732 deaths. The mean (+/- SD) age at baseline was 66.6 +/- 9.3 y. Median nut consumption was 1 serving/wk. Multivariable-adjusted HRs (95% CIs) were 1.0 (reference), 0.92 (0.83, 1.01), 0.85 (0.76, 0.96), 0.86 (0.75, 0.98), and 0.74 (0.63, 0.87) for nut consumption of never or <1 serving/mo, 1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and >= 5 servings/wk, respectively (P-linear trend < 0.0001), after adjustment for age, body mass index, alcohol use, smoking, exercise, prevalent diabetes and hypertension, and intakes of energy, saturated fat, fruit and vegetables, and red meat. In a secondary analysis, results were consistent for cardiovascular disease mortality but only suggestive and non-statistically significant for coronary artery disease and cancer mortality. Conclusion: Our data are consistent with an inverse association between nut consumption and the risk of all-cause and cardiovascular disease mortality in US male physicians. C1 [Hshieh, Tammy T.; Petrone, Andrew B.; Gaziano, J. Michael; Djousse, Luc] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Hshieh, Tammy T.] Inst Aging Res, Aging Brain Ctr, Boston, MA USA. [Gaziano, J. Michael; Djousse, Luc] Geriatr Res GRECC, Massachusetts Vet Epidemiol, Boston, MA USA. [Gaziano, J. Michael; Djousse, Luc] Geriatr Res GRECC, Res Informat Ctr MAVERIC, Boston, MA USA. [Gaziano, J. Michael; Djousse, Luc] VA Boston Healthcare Syst, Boston, MA USA. RP Djousse, L (reprint author), Brigham & Womens Hosp, Div Aging, One Brigham Circle,1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM ldjousse@rics.bwh.harvard.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD [R21 HL088081]; National Cancer Institute [CA-34944, CA-40360, CA-097193]; NHLBI [HL-26490, HL-34595]; NTH-funded T32 training grant [AG000158] FX Supported by grant R21 HL088081 from the National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD (to LD). The Physicians' Health Study is supported by grants CA-34944, CA-40360, and CA-097193 from the National Cancer Institute and grants HL-26490 and HL-34595 from the NHLBI. TTH is supported by an NTH-funded T32 training grant (AG000158). NR 60 TC 8 Z9 8 U1 0 U2 15 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2015 VL 101 IS 2 BP 407 EP 412 DI 10.3945/ajcn.114.099846 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CA5US UT WOS:000348973900021 PM 25646339 ER PT J AU Berkowitz, SA Meigs, JB DeWalt, D Seligman, HK Barnard, LS Bright, OJM Schow, M Atlas, SJ Wexler, DJ AF Berkowitz, Seth A. Meigs, James B. DeWalt, Darren Seligman, Hilary K. Barnard, Lily S. Bright, Oliver-John M. Schow, Marie Atlas, Steven J. Wexler, Deborah J. TI Material Need Insecurities, Control of Diabetes Mellitus, and Use of Health Care Resources Results of the Measuring Economic Insecurity in Diabetes Study SO JAMA INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; FOOD INSECURITY; LOW-INCOME; SENSITIVE-CONDITIONS; SOCIOECONOMIC DISPARITIES; CARDIOVASCULAR-DISEASE; SOCIAL DETERMINANTS; HOUSING INSTABILITY; SELF-MANAGEMENT; ADULTS AB IMPORTANCE Increasing access to care may be insufficient to improve the health of patients with diabetes mellitus and unmet basic needs (hereinafter referred to as material need insecurities). How specific material need insecurities relate to clinical outcomes and the use of health care resources in a setting of near-universal access to health care is unclear. OBJECTIVE To determine the association of food insecurity, cost-related medication underuse, housing instability, and energy insecurity with control of diabetes mellitus and the use of health care resources. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional data were collected from June 1, 2012, through October 31, 2013, at 1 academic primary care clinic, 2 community health centers, and 1 specialty center for the treatment of diabetes mellitus in Massachusetts. A random sample of 411 patients, stratified by clinic, consisted of adults (aged >= 21 years) with diabetes mellitus (response rate, 62.3%). MAIN OUTCOMES AND MEASURES The prespecified primary outcome was a composite indicator of poor diabetes control (hemoglobin A(1c) level, >9.0%; low-density lipoprotein cholesterol level, >100mg/dL; or blood pressure, >140/90 mm Hg). Prespecified secondary outcomes included outpatient visits and a composite of emergency department (ED) visits and acute care hospitalizations (ED/inpatient visits). RESULTS Overall, 19.1% of respondents reported food insecurity; 27.6%, cost-related medication underuse; 10.7%, housing instability; 14.1%, energy insecurity; and 39.1%, at least 1 material need insecurity. Poor diabetes control was observed in 46.0% of respondents. In multivariable models, food insecurity was associated with a greater odds of poor diabetes control (adjusted odds ratio [OR], 1.97 [95% CI, 1.58-2.47]) and increased outpatient visits (adjusted incident rate ratio [IRR], 1.19 [95% CI, 1.05-1.36]) but not increased ED/inpatient visits (IRR, 1.00 [95% CI, 0.51-1.97]). Cost-related medication underuse was associated with poor diabetes control (OR, 1.91 [95% CI, 1.35-2.70]) and increased ED/inpatient visits (IRR, 1.68 [95% CI, 1.21-2.34]) but not outpatient visits (IRR, 1.07 [95% CI, 0.95-1.21]). Housing instability (IRR, 1.31 [95% CI, 1.14-1.51]) and energy insecurity (IRR, 1.12 [95% CI, 1.00-1.25]) were associated with increased outpatient visits but not with diabetes control (OR, 1.10 [95% CI, 0.60-2.02] and OR, 1.27 [95% CI, 0.96-1.69], respectively) or with ED/inpatient visits (IRR, 1.49 [95% CI, 0.81-2.73] and IRR, 1.31 [95% CI, 0.80-2.13], respectively). An increasing number of insecurities was associated with poor diabetes control (OR for each additional need, 1.39 [95% CI, 1.18-1.63]) and increased use of health care resources (IRR for outpatient visits, 1.09 [95% CI, 1.03-1.15]; IRR for ED/inpatient visits, 1.22 [95% CI, 0.99-1.51]). CONCLUSIONS AND RELEVANCE Material need insecurities were common among patients with diabetes mellitus and had varying but generally adverse associations with diabetes control and the use of health care resources. Material need insecurities may be important targets for improving care of diabetes mellitus. C1 [Berkowitz, Seth A.; Meigs, James B.; Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02141 USA. [Berkowitz, Seth A.; Wexler, Deborah J.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02141 USA. [Berkowitz, Seth A.; Meigs, James B.; Atlas, Steven J.; Wexler, Deborah J.] Harvard Univ, Sch Med, Boston, MA USA. [DeWalt, Darren] Univ N Carolina, Sch Med, Div Gen Med & Clin Epidemiol, Chapel Hill, NC USA. [Seligman, Hilary K.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Seligman, Hilary K.] San Francisco Gen Hosp & Trauma Ctr, Ctr Vulnerable Populat, San Francisco, CA USA. RP Berkowitz, SA (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,Ninth Floor, Boston, MA 02141 USA. EM saberkowitz@partners.org OI Berkowitz, Seth/0000-0003-1030-4297; DeWalt, Darren/0000-0003-2270-751X FU Institutional National Research Service award [T32HP10251]; Ryoichi Sasakawa Fellowship Fund; Division of General Internal Medicine, Massachusetts General Hospital; National Institutes of Health [R03DK090196-01A1, U01DK098246, K24DK080140] FX This study was supported by Institutional National Research Service award T32HP10251 (Dr Berkowitz), by the Ryoichi Sasakawa Fellowship Fund (Dr Berkowitz), by the Division of General Internal Medicine, Massachusetts General Hospital (Dr Berkowitz), by awards R03DK090196-01A1 and U01DK098246 from the National Institutes of Health (DrWexler), and in part by award K24DK080140 from the National Institutes of Health (Dr Meigs). NR 53 TC 15 Z9 15 U1 4 U2 16 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 FEB PY 2015 VL 175 IS 2 BP 257 EP 265 DI 10.1001/jamainternmed.2014.6888 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CA7TL UT WOS:000349120100026 PM 25545780 ER PT J AU Sebro, R Aslam, R Muglia, VF Wang, ZJ Westphalen, AC AF Sebro, Ronnie Aslam, Rizwan Muglia, Valdair Francisco Wang, Z. Jane Westphalen, Antonio Carlos TI Low yield of chemical shift MRI for characterization of adrenal lesions with high attenuation density on unenhanced CT SO ABDOMINAL IMAGING LA English DT Article DE Adrenal adenoma; Adrenal lesion; Adrenal nodule; Adrenal mass; Chemical shift; Magnetic resonance imaging (MRI); Computed tomography (CT) ID DELAYED ENHANCED CT; INITIAL-EXPERIENCE; F-18-FDG PET/CT; IN-PHASE; MASSES; PHEOCHROMOCYTOMA; ADENOMAS; BENIGN; DIFFERENTIATION; METASTASES AB Purpose: To investigate the threshold unenhanced CT density of adrenal nodules at which further evaluation with chemical shift MRI is unlikely to be definitive and therefore not helpful in further characterizing some indeterminate adrenal lesions. Methods: Retrospective evaluation of 44 adrenal lesions imaged with unenhanced CT and chemical shift MRI and followed for at least 1 year. Qualitative and quantitative assessment of signal loss on chemical shift MRI was performed. Adenomas were diagnosed if the lesion measured equal or less than 10 HU on unenhanced CT; on MRI a SI index greater than 16.5% or adrenal: spleen chemical shift ratio less than 0.71 was considered diagnostic of adenoma. Results: 31.8% (14/44), 47.7% (21/44), and 20.5% (9/44) of the adrenal lesions had an unenhanced CT attenuation density <= 10, 10-30, and > 30 HU. Adrenal lesions with an unenhanced CT density 10-30 and > 30 HU had a 76.2% (16/21) and a 33.3% (3/9) chance of being categorized as an adenoma using MRI SI index, respectively. Conclusions: Adrenal lesions with unenhanced attenuation CT density > 30 HU had a 66.6% of remaining indeterminate even after evaluation with chemical shift MRI. Advances in knowledge: Chemical shift MRI is reasonable for evaluating adrenal lesions with an unenhanced CT attenuation density less than 30 HU. The likelihood of chemical shift MRI detecting signal loss in lesions CT density greater than 30 HU, however, is low. C1 [Sebro, Ronnie] Massachusetts Gen Hosp Imaging, Boston, MA 02114 USA. [Aslam, Rizwan; Wang, Z. Jane; Westphalen, Antonio Carlos] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Aslam, Rizwan; Wang, Z. Jane; Westphalen, Antonio Carlos] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Muglia, Valdair Francisco] Univ Sao Paulo, Ribeirao Preto Sch Med, BR-14048900 Ribeirao Preto, SP, Brazil. RP Westphalen, AC (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM antonio.west-phalen@ucsf.edu RI Muglia, Valdair/H-5208-2012 OI Muglia, Valdair/0000-0002-4700-0599 NR 35 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD FEB PY 2015 VL 40 IS 2 BP 318 EP 326 DI 10.1007/s00261-014-0208-8 PG 9 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA AZ6AC UT WOS:000348298800012 PM 25095753 ER PT J AU Suh, CH Baheti, AD Tirumani, SH Rosenthal, MH Kim, KW Ramaiya, NH Shinagare, AB AF Suh, Chong Hyun Baheti, Akshay D. Tirumani, Sree Harsha Rosenthal, Michael H. Kim, Kyung Won Ramaiya, Nikhil H. Shinagare, Atul B. TI Multimodality imaging of penile cancer: what radiologists need to know SO ABDOMINAL IMAGING LA English DT Article DE Penile cancer; 2010 AJCC TNM staging; Role of imaging; Management ID SQUAMOUS-CELL CARCINOMA; METASTASIS CLASSIFICATION-SYSTEM; LYMPH-NODE METASTASIS; HUMAN-PAPILLOMAVIRUS; ASPIRATION-CYTOLOGY; PROGNOSTIC-FACTORS; SURGICAL-TREATMENT; GROIN DISSECTION; PHASE-II; LYMPHADENECTOMY AB The purpose of this article is to provide a comprehensive update on the role of imaging in the diagnosis and management of penile cancer. Imaging plays a major role in the initial assessment, treatment planning, and follow-up of patients with penile carcinoma. MRI helps in assessing the T staging of the primary and in detecting local recurrence. PET/CT and CT are useful for detecting regional nodal and distant metastases. C1 [Suh, Chong Hyun; Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul 138736, South Korea. [Suh, Chong Hyun; Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, Seoul 138736, South Korea. [Baheti, Akshay D.; Tirumani, Sree Harsha; Rosenthal, Michael H.; Ramaiya, Nikhil H.; Shinagare, Atul B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Baheti, Akshay D.; Tirumani, Sree Harsha; Rosenthal, Michael H.; Ramaiya, Nikhil H.; Shinagare, Atul B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Suh, CH (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, 88 Olymp Ro 43 Gil, Seoul 138736, South Korea. EM jhsuh04@gmail.com RI Rosenthal, Michael/D-4080-2015 NR 58 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD FEB PY 2015 VL 40 IS 2 BP 424 EP 435 DI 10.1007/s00261-014-0218-6 PG 12 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA AZ6AC UT WOS:000348298800021 PM 25117563 ER PT J AU Malchau, H Graves, SE Porter, M Harris, WH Troelsen, A AF Malchau, Henrik Graves, Stephen E. Porter, Martyn Harris, William H. Troelsen, Anders TI The next critical role of orthopedic registries SO ACTA ORTHOPAEDICA LA English DT Editorial Material C1 [Malchau, Henrik; Harris, William H.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Dept Orthoped, Boston, MA 02114 USA. [Malchau, Henrik] Sahlgrens Univ Hosp, Dept Orthoped, Molndal, Sweden. [Graves, Stephen E.] Australian Orthopaed Assoc Natl Joint Replacement, Adelaide, SA, Australia. [Graves, Stephen E.] Flinders Univ S Australia, Dept Surg, Adelaide, SA 5001, Australia. [Porter, Martyn] Wrightington Hosp, Wigan, Lancs, England. [Troelsen, Anders] Copenhagen Univ Hosp Hvidovre, Clin Orthopaed Res Hvidovre CORH, Dept Orthopaed Surg, Copenhagen, Denmark. RP Malchau, H (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, Dept Orthoped, Boston, MA 02114 USA. EM hmalchau@mgh.harvard.edu RI Graves, Stephen/A-9463-2016 OI Graves, Stephen/0000-0002-1629-319X NR 3 TC 3 Z9 3 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1745-3674 EI 1745-3682 J9 ACTA ORTHOP JI Acta Orthop. PD FEB PY 2015 VL 86 IS 1 BP 3 EP 4 DI 10.3109/17453674.2014.1002184 PG 2 WC Orthopedics SC Orthopedics GA AZ6ZD UT WOS:000348367000002 PM 25583041 ER PT J AU Goy, ER Bohlig, A Carter, J Ganzini, L AF Goy, Elizabeth R. Bohlig, Amanda Carter, Julie Ganzini, Linda TI Identifying Predictors of Hospice Eligibility in Patients With Parkinson Disease SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE Parkinson disease; hospice; palliative ID BODY-WEIGHT; PROGRESSION; MORTALITY; LIFE; CARE; END AB This study aims to improve recognition of hospice eligibility for patients with Parkinson disease (PD) by ascertaining which variables have a higher probability of occurring uniquely in 6 to 12 months before death when compared to 18 to 24 months before death. Participants were 339 patients who died who were diagnosed with PD or Parkinsonism and treated with dopaminergic prescriptions for at least 3 years in northwestern US Veterans Affairs medical centers. A range of indicators were compared across 3 time periods (30-36 months, 24-18 months, and 12-6 months before death) using within-subjects repeated measures design. Results indicate that body mass index less than 18, alone or combined with a shift in prescribing (when benefits of dopaminergic medications no longer outweigh their risk of side effects), may signal appropriate timing for hospice referral. C1 [Goy, Elizabeth R.; Bohlig, Amanda; Ganzini, Linda] Portland VA Med Ctr, Div Mental Hlth, Portland, OR 97239 USA. [Carter, Julie] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. RP Goy, ER (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd P3MHDC, Portland, OR 97239 USA. EM Elizabeth.Goy@va.gov FU Health Services Research and Development (HSR&D) Career Development Award [RCD 04326]; HSR&D Portland Center for the Study of Chronic, Comorbid Mental and Physical Disorders, at the Portland VA Medical Center [REA 06-174] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research is funded in part by a Health Services Research and Development (HSR&D) Career Development Award for Dr. Goy (RCD 04326), and the HSR&D Portland Center for the Study of Chronic, Comorbid Mental and Physical Disorders (REA 06-174), at the Portland VA Medical Center. NR 18 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 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD FEB PY 2015 VL 32 IS 1 BP 29 EP 33 DI 10.1177/1049909113502119 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ4MQ UT WOS:000348196000004 PM 23975684 ER PT J AU Clark, JK Fasciano, K AF Clark, Jennifer K. Fasciano, Karen TI Young Adult Palliative Care: Challenges and Opportunities SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Review DE young adult; emerging adult; adolescents and young adults; palliative care; hospice; end-of-life care ID OF-LIFE CARE; CYSTIC-FIBROSIS; DYING ADOLESCENT; SELF-MANAGEMENT; CANCER-PATIENTS; CHRONIC ILLNESS; TRANSITION; CHILDREN; DISEASE; PEOPLE AB Young adulthood is a time of immense growth and possibilities. As a result, it is also a time when serious illness can have profound effects. This review examines the current data pertinent to young adult palliative care and discusses the challenges and opportunities where palliative medicine can enhance the care provided to this growing and vulnerable population. From the data, 2 primary themes emerged (1) ongoing young adult development not only generates unique biologic disease burdens and clinical treatment options but also requires frequent assessment and promotion and (2) binary health care systems often leave young adults without access to developmentally appropriate health care. Given its interdisciplinary approach, palliative care is uniquely poised to address the challenges known to caring for the seriously ill young adult. C1 [Clark, Jennifer K.] Univ Oklahoma, Dept Internal Med, Sch Community Med Tulsa, OU Ctr Palliat Care, Tulsa, OK 74135 USA. [Clark, Jennifer K.] Univ Oklahoma, Dept Pediat, Sch Community Med Tulsa, OU Ctr Palliat Care, Tulsa, OK 74135 USA. [Fasciano, Karen] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Clark, JK (reprint author), Univ Oklahoma, Dept Internal Med, Sch Community Med Tulsa, OU Ctr Palliat Care, 4502 E 41st St, Tulsa, OK 74135 USA. EM jennifer-k-clark@ouhsc.edu NR 80 TC 2 Z9 2 U1 2 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD FEB PY 2015 VL 32 IS 1 BP 101 EP 111 DI 10.1177/1049909113510394 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ4MQ UT WOS:000348196000013 PM 24198063 ER PT J AU Simon, HB AF Simon, Harvey B. TI Music as Medicine SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID BRAIN; INTERVENTION; METAANALYSIS; DEPRESSION; RECOVERY; CANCER; MOOD; GAIT; PAIN C1 [Simon, Harvey B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Simon, Harvey B.] MIT, Hlth Sci Technol Fac, Cambridge, MA 02139 USA. [Simon, Harvey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Simon, HB (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. EM hsimon@partners.org NR 32 TC 0 Z9 0 U1 3 U2 22 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 FEB PY 2015 VL 128 IS 2 BP 208 EP 210 DI 10.1016/j.amjmed.2014.10.023 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AZ5YG UT WOS:000348293800027 PM 25448175 ER PT J AU Wosu, AC Gelaye, B Valdimarsdottir, U Kirschbaum, C Stalder, T Shields, AE Williams, MA AF Wosu, Adaeze C. Gelaye, Bizu Valdimarsdottir, Unnur Kirschbaum, Clemens Stalder, Tobias Shields, Alexandra E. Williams, Michelle A. TI Hair cortisol in relation to sociodemographic and lifestyle characteristics in a multiethnic US sample SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Correlates; Race; Ethnicity; Chronic stress; Biomarker; Community ID INDIVIDUALS AB Purpose: We investigated the feasibility of obtaining hair samples from men and women at community-based barbershops and hair salons for analysis of cortisol and assessed sociodemographic and lifestyle correlates of hair cortisol concentrations (HCCs). A total of 102 participants completed the study. Methods: Research staff interviewed participants using a structured questionnaire, and samples of hair were collected. HCCs were determined using liquid chromatography-tandem mass spectrometry. Age- and sex-adjusted linear regression models were used to evaluate the association of HCC with covariates. Results:: Analyses by race/ethnicity showed highest median HCC in blacks (12.5 [6.9-29.31) pg/mg) followed by Hispanics (10.7 15.8-14.91 pg/mg), whites (5.0 [3.8-10.8] pg/mg), and other participants (4.2 [3.3-15.71 pg/mg), P < .01. Current smokers had significantly higher median HCC (11.7 [8.8-18.91 pg/mg) compared with former smokers (4.6 [3.5-14.6] pg/mg) and those who had never smoked (6.9 [4.7-12.81 pg/mg), P = .04. After adjustment for age and sex, geometric mean HCC was 0.72 pg/mg lower in dyed hair compared with hair that was not dyed (beta = 0.72, standard error = 0.30, 95% confidence interval, -1.29 to -0.15, P = .02). Conclusions: HCC can be assessed in community-based studies. Future HCC studies should consider cosmetic hair treatment, cigarette smoking, and the potential role of psychosocial stressors in the association between race/ethnicity and HCC. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wosu, Adaeze C.; Gelaye, Bizu; Valdimarsdottir, Unnur; Williams, Michelle A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Valdimarsdottir, Unnur] Univ Iceland, Fac Med, Ctr Publ Hlth Sci, Reykjavik, Iceland. [Kirschbaum, Clemens; Stalder, Tobias] Tech Univ Dresden, Dept Psychol, D-01062 Dresden, Germany. [Shields, Alexandra E.] Harvard Univ, Sch Med, Harvard Massachusetts Gen Hosp,Dept Med, Ctr Genom Vulnerable Populat & Hlth Dispar,Mongan, Boston, MA USA. RP Wosu, AC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Room 500, Boston, MA 02115 USA. EM awosu@hsph.harvard.edu OI Gelaye, Bizu/0000-0001-7934-548X FU National Institutes of Health; National Center for Research Resources (NCRR); National Center for Advancing Translational Sciences (NCATS) [8UL1TR000170-05] FX This research was supported, in part, by an award from the National Institutes of Health, National Center for Research Resources (NCRR) and the National Center for Advancing Translational Sciences (NCATS): 8UL1TR000170-05. The National Institutes of Health had no further role in the study design, in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the article for publication. The authors would like to thank the study participants, owners, managers, and staff of the barbershops and hair salons for granting access to conduct the study and the laboratory staff at the Department of Biopsychology, Technical University of Dresden, Dresden, Germany, for completing all laboratory analyses. The authors also wish to thank Ms. Kristin Roynesdal for her assistance with data collection. NR 20 TC 12 Z9 12 U1 0 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 2015 VL 25 IS 2 BP 90 EP 95 DI 10.1016/j.annepidem.2014.11.022 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CA2QE UT WOS:000348751700005 PM 25534254 ER PT J AU Balch, C Arias-Pulido, H Banerjee, S Lancaster, AK Clark, KB Perilstein, M Hawkins, B Rhodes, J Sliz, P Wilkins, J Chittenden, TW AF Balch, Curt Arias-Pulido, Hugo Banerjee, Soumya Lancaster, Alex K. Clark, Kevin B. Perilstein, Michael Hawkins, Brian Rhodes, John Sliz, Piotr Wilkins, Jon Chittenden, Thomas W. TI Science and technology consortia in US biomedical research: A paradigm shift in response to unsustainable academic growth SO BIOESSAYS LA English DT Editorial Material C1 [Balch, Curt; Arias-Pulido, Hugo; Banerjee, Soumya; Lancaster, Alex K.; Clark, Kevin B.; Perilstein, Michael; Hawkins, Brian; Rhodes, John; Sliz, Piotr; Wilkins, Jon; Chittenden, Thomas W.] Complex Biol Syst Alliance, N Andover, MA 01845 USA. [Balch, Curt; Arias-Pulido, Hugo; Banerjee, Soumya; Lancaster, Alex K.; Wilkins, Jon; Chittenden, Thomas W.] Ronin Inst, Montclair, NJ USA. [Banerjee, Soumya] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Banerjee, Soumya] Broad Inst MIT & Harvard, Cambridge, MA USA. [Lancaster, Alex K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Clark, Kevin B.] Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA USA. [Clark, Kevin B.] Univ Illinois, Natl Ctr Supercomp Applicat, Urbana, IL USA. [Hawkins, Brian] Univ Washington, Sch Med, Mitochondria & Metab Ctr, Seattle, WA USA. [Rhodes, John] Yale Univ, Sch Med, Yale Cardiovasc Res Ctr, New Haven, CT USA. [Sliz, Piotr] Harvard Univ, Sch Med, SBGrid Consortium, Boston, MA USA. [Wilkins, Jon] Santa Fe Inst, Santa Fe, NM 87501 USA. [Chittenden, Thomas W.] Harvard Univ, Sch Med, Res Comp Grp, Boston, MA USA. RP Chittenden, TW (reprint author), Complex Biol Syst Alliance, N Andover, MA 01845 USA. EM tom_chittenden@hms.harvard.edu RI Lancaster, Alexander/K-2855-2013; OI Wilkins, Jon/0000-0001-6405-6538; Lancaster, Alexander/0000-0002-0002-9263; Sliz, Piotr/0000-0002-6522-0835 NR 10 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0265-9247 EI 1521-1878 J9 BIOESSAYS JI Bioessays PD FEB PY 2015 VL 37 IS 2 BP 119 EP 122 DI 10.1002/bies.201400167 PG 4 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA AZ9AQ UT WOS:000348504100004 PM 25387399 ER PT J AU Appelbaum, FR Anasetti, C Antin, JH Atkins, H Davies, S Devine, S Giralt, S Heslop, H Laport, G Lee, SJ Loganw, B Pasquini, M Pulsipher, M Stadtmauer, E Wingard, JR Horowitz, MM AF Appelbaum, Frederick R. Anasetti, Claudio Antin, Joseph H. Atkins, Harold Davies, Stella Devine, Steven Giralt, Sergio Heslop, Helen Laport, Ginna Lee, Stephanie J. Loganw, Brent Pasquini, Marcelo Pulsipher, Michael Stadtmauer, Edward Wingard, John R. Horowitz, Mary M. TI Blood and Marrow Transplant Clinical Trials Network State of the Science Symposium 2014 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic cell; transplantation; Leukemia; Lymphoma; Myeloma ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; BRONCHIOLITIS OBLITERANS SYNDROME; IDIOPATHIC PNEUMONIA SYNDROME; ACUTE MYELOID-LEUKEMIA; SEVERE APLASTIC-ANEMIA; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; UNRELATED DONOR TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; SIALIDASE FUSION PROTEIN C1 [Appelbaum, Frederick R.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Anasetti, Claudio] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Atkins, Harold] Ottawa Hosp, Res Inst, Canc Therapeut Program, Ottawa, ON, Canada. [Davies, Stella] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Devine, Steven] Ohio State Univ, Blood & Marrow Transplant Program, Columbus, OH 43210 USA. [Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Bone Marrow Transplant Serv, New York, NY 10021 USA. [Heslop, Helen] Baylor Coll Med, Adult Bone Marrow & Stem Cell Transplant Program, Houston, TX 77030 USA. [Laport, Ginna] Stanford Hosp & Clin, Stanford, CA USA. [Loganw, Brent; Pasquini, Marcelo; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Div Clin Res, Milwaukee, WI 53226 USA. [Pulsipher, Michael] Univ Utah, Sch Med, Primary Childrens Hosp, Salt Lake City, UT USA. [Stadtmauer, Edward] Univ Penn, Div Hematol & Oncol, Philadelphia, PA 19104 USA. [Wingard, John R.] Univ Florida, Dept Internal Med, Div Hematol, Gainesville, FL USA. RP Appelbaum, FR (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,D5-310, Seattle, WA 98109 USA. EM fappelba@fhcrc.org FU National Heart, Lung, and Blood Institute [U10HL069294]; National Cancer Institute [U10HL069294]; Be The Match Foundation [U10HL069294] FX Support was provided by grant #U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute (Grant # U10HL069294) and by the Be The Match Foundation (Grant # U10HL069294). NR 140 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2015 VL 21 IS 2 BP 202 EP 224 DI 10.1016/j.bbmt.2014.10.003 PG 23 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CA0UW UT WOS:000348632700003 PM 25445636 ER PT J AU Arai, S Arora, M Wang, T Spellman, SR He, W Courie, DR Urbano-Ispizua, A Cutler, CS Bacigalupo, AA Battiwallaw, M Flowers, ME Juckett, MB Lee, SJ Loren, AW Klumpp, TR Prockup, SE Ringden, OETH Savani, BN Socie, G Schultz, KR Spitzer, T Teshima, T Bredeson, CN Jacobsohn, DA Hayashi, RJ Drobyski, WR Frangoul, HA Akpek, G Ho, VT Lewis, VA Gale, RP Koreth, J Chao, NJ Aljurf, MD Cooper, BW Laughlin, MJ Hsu, JW Hematti, P Verdonck, LF Solh, MM Norkin, M Reddy, V Perez-Simon, JA Khera, N Lewis, ID Atsuta, Y Olsson, RF Saber, W Waller, EK Blaise, D Pidala, JA Martin, PJ Satwani, P Bornhauser, M Inamoto, Y Weisdorf, DJ Horowitz, MM Pavletic, SZ AF Arai, Sally Arora, Mukta Wang, Tao Spellman, Stephen R. He, Wensheng Courie, Daniel R. Urbano-Ispizua, Alvaro Cutler, Corey S. Bacigalupo, Andrea A. Battiwallaw, Minoo Flowers, Mary E. Juckett, Mark B. Lee, Stephanie J. Loren, Alison W. Klumpp, Thomas R. Prockup, Susan E. Ringden, Olle E. T. H. Savani, Bipin N. Socie, Gerard Schultz, Kirk R. Spitzer, Thomas Teshima, Takanori Bredeson, Christopher N. Jacobsohn, David A. Hayashi, Robert J. Drobyski, William R. Frangoul, Haydar A. Akpek, Gorgiin Ho, Vincent T. Lewis, Victor A. Gale, Robert Peter Koreth, John Chao, Nelson J. Aljurf, Mahmoud D. Cooper, Brenda W. Laughlin, Mary J. Hsu, Jack W. Hematti, Peiman Verdonck, Leo F. Solh, Melhelm M. Norkin, Maxim Reddy, Vijay Perez-Simon, Jose A. Khera, Nandita Lewis, Ian D. Atsuta, Yoshiko Olsson, Richard F. Saber, Wael Waller, Edmund K. Blaise, Didier Pidala, Joseph A. Martin, Paul J. Satwani, Prakash Bornhauser, Martin Inamoto, Yoshihiro Weisdorf, Daniel J. Horowitz, Mary M. Pavletic, Steven Z. CA Graft-Vs-Host Dis Working Comm CIB TI Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation: A Report from the Center for International Blood and Marrow Transplant Research SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Incidence; cGVHD; Allogeneic transplant; Nonrelapse mortality ID HEMATOPOIETIC-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; BONE-MARROW; UNRELATED DONORS; STEM-CELL; REDUCED-INTENSITY; CLINICAL-TRIALS; COMPETING RISKS; SINGLE-CENTER AB Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P <.0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Arai, Sally; Arora, Mukta; Wang, Tao] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Arora, Mukta] Univ Minnesota, Med Ctr, Div Hematol Oncol & Transplant, Minneapolis, MN 55455 USA. [Wang, Tao] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA. [Wang, Tao] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Natl Marrow Donor Program, Minneapolis, MN USA. [He, Wensheng; Loren, Alison W.] Univ Michigan, Div Hematol Oncol, Ann Arbor, MI USA. [Loren, Alison W.; Spitzer, Thomas] Hosp Clin Barcelona, Div Hematol Oncol, Barcelona, Spain. [Socie, Gerard; Bredeson, Christopher N.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Teshima, Takanori; Waller, Edmund K.] IRCCS AOU San Martino IST, Dept Hematol, Genoa, Italy. [Loren, Alison W.; Hematti, Peiman; Satwani, Prakash] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Koreth, John; Norkin, Maxim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Koreth, John; Perez-Simon, Jose A.] Univ Washington, Seattle, WA 98195 USA. [Aljurf, Mahmoud D.; Cooper, Brenda W.; Laughlin, Mary J.] Univ Wisconsin, Hosp & Clin, Dept Med, Div Hematol Oncol Bone Marrow Transplantat, Madison, WI 53792 USA. [Hematti, Peiman; Verdonck, Leo F.; Solh, Melhelm M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Hematti, Peiman; Solh, Melhelm M.; Norkin, Maxim] Univ Penn, Med Ctr, Abramson Canc Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Reddy, Vijay; Perez-Simon, Jose A.; Khera, Nandita] Temple Bone Marrow Transplant Program, Div Bone Marrow Transplantat, Philadelphia, PA USA. [Lewis, Ian D.; Atsuta, Yoshiko; Olsson, Richard F.] Mem Sloan Kettering Canc Ctr, Dept Pediat, Div Bone Marrow Transplant, New York, NY 10021 USA. [Saber, Wael; Waller, Edmund K.; Blaise, Didier] Karolinska Univ Hosp, Div Clin Immunol, Stockholm, Sweden. [Saber, Wael; Waller, Edmund K.; Blaise, Didier] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Pidala, Joseph A.; Martin, Paul J.; Satwani, Prakash] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN 37235 USA. [Martin, Paul J.] Hop St Louis, Div Hematol, Paris, France. [Satwani, Prakash; Bornhauser, Martin] Univ British Columbia, British Columbias Childrens Hosp, Dept Pediat Hematol Oncol BMT, Vancouver, BC V5Z 1M9, Canada. [Bornhauser, Martin; Inamoto, Yoshihiro] Massachusetts Gen Hosp, Dept Bone Marrow Transplant Oncol, Boston, MA 02114 USA. [Inamoto, Yoshihiro; Weisdorf, Daniel J.] Kyushu Univ Hosp, Fukuoka 812, Japan. [Horowitz, Mary M.] Ottawa Hosp, Dept Med, Ottawa, ON, Canada. [Horowitz, Mary M.; Pavletic, Steven Z.] Childrens Natl Hlth Syst, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC USA. [Pavletic, Steven Z.; Graft-Vs-Host Dis Working Comm CIB] Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO USA. RP Pavletic, SZ (reprint author), NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, 9000 Rockville Pike,Bldg 10 CRC,Room 3E-3330, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov RI IBIS, ONCOHEMATOLOGI/P-3457-2015; OI Olsson, Richard/0000-0001-5970-2128 FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung, and Blood Institute (NHLBI) [U24-CA76518]; National Institute of Allergy and Infectious Diseases (NIAID) [U24-CA76518]; NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; 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; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; Medical College of Wisconsin; Merck 82 Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; Therakos; WellPoint The views expressed in this article do not reflect the official policy or position of the NIH; Department of the Navy; Department of Defense, or any other agency of the U.S. Government FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) (U24-CA76518), and the National Institute of Allergy and Infectious Diseases (NIAID) (U24-CA76518); Grant/Cooperative Agreement 5U01HL069294 from the NHLBI and NCI; contract HHSH234200637015C with Health Resources and Services Administration; 2 grants (N00014-06-1-0704 and N00014-08-1-0058) from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; 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; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Medical College of Wisconsin; Merck 82 Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; Therakos; and WellPoint The views expressed in this article do not reflect the official policy or position of the NIH, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. NR 32 TC 41 Z9 44 U1 1 U2 6 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 FEB PY 2015 VL 21 IS 2 BP 266 EP 274 DI 10.1016/j.bbmt.2014.10.021 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CA0UW UT WOS:000348632700009 PM 25445023 ER PT J AU Bona, K London, WB Guo, DJ Abel, G Lehmann, L Wolfe, J AF Bona, Kira London, Wendy B. Guo, Dongjing Abel, Gregory Lehmann, Leslie Wolfe, Joanne TI Prevalence and Impact of Financial Hardship among New England Pediatric Stem Cell Transplantation Families SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Pediatric; Hematopoietic stem cell transplantation; Financial hardship; Graft-versus-host disease; Poverty ID QUALITY-OF-LIFE; LOW-INCOME; CHILD HEALTH; MULTISITE SURVEILLANCE; SOCIOECONOMIC-STATUS; CANCER-TREATMENT; CYSTIC-FIBROSIS; ECONOMIC-IMPACT; FOOD SECURITY; COSTS AB Poverty is correlated with negative health outcomes in pediatric primary care and subspecialties; its association with childhood hematopoietic stem cell transplantation (HSCT) patterns of care and clinical outcomes is not known. We describe family-reported financial hardship at a primary referral center in New England and explore the relationship between measures of poverty and patterns of care and clinical outcomes. Forty-five English-speaking parents of children after allogeneic HSCT in the prior 12 months completed a 1-time survey (response rate 88%). Low-income families, defined as <= 200% federal poverty level (FPL), were compared with all others. Eighteen (40%) families reported pre-HSCT incomes <= 200% FPL. Material hardship, including food, housing, or energy insecurity was reported by 17 (38%) families in the cohort. Low-income families reported disproportionate transplantation-related income losses, with 7 (39%) reporting annual income losses of >40% compared with 2 (18%) wealthier families (P = .02). In univariate analyses, 11(61%) low-income children experienced graft-versus-host disease (GVHD) of any grade in the first 180 days after HSCT compared with 2 (7%) wealthier children (P = .004). We conclude that low income and, in particular, material hardship, are prevalent in a New England pediatric HSCT population and represent targets for improvement in quality of life. The role of poverty in mediating GVHD deserves further investigation in larger studies that can control for known risk factors and may provide a targetable source of transplantation-associated morbidity. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Bona, Kira; London, Wendy B.; Guo, Dongjing; Lehmann, Leslie; Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Bona, Kira; London, Wendy B.; Guo, Dongjing; Lehmann, Leslie; Wolfe, Joanne] Dana Farber Boston Childrens Canc & Blood Disorde, Dept Pediat Oncol, Boston, MA USA. [Bona, Kira; London, Wendy B.; Abel, Gregory; Lehmann, Leslie; Wolfe, Joanne] Harvard Univ, Sch Med, Boston, MA USA. [Bona, Kira; Abel, Gregory; Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Populat Res, Boston, MA 02115 USA. [Abel, Gregory] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Oncol, Boston, MA 02115 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Bona, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM kira.bona@childrens.harvard.edu FU Family Reach Foundation; Pedals for Pediatrics; St. Baldrick's Foundation; National Palliative Care Research Center; American Society of Clinical Oncology FX The authors thank our families for sharing their time and stories with us. The authors additionally thank Dr. Deborah Frank and colleagues for sharing their research experience and measurement instruments. This study was funded in part by grants from the Family Reach Foundation and Pedals for Pediatrics. Dr. Bona is supported by grants from the St. Baldrick's Foundation, the National Palliative Care Research Center, and the American Society of Clinical Oncology. NR 48 TC 5 Z9 5 U1 4 U2 8 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 FEB PY 2015 VL 21 IS 2 BP 312 EP 318 DI 10.1016/j.bbmt.2014.10.016 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CA0UW UT WOS:000348632700016 PM 25445021 ER PT J AU Vij, R Kumar, S Zhang, MJ Zhong, XB Huang, JX Dispenzieri, A Abidi, MH Bird, JM Freytes, CO Gale, RP Kindwall-Keller, TL Kyle, RA Landsburg, DJ Lazarus, HM Munker, R Roy, V Sharma, M Vogl, DT Wirk, B Hari, PN AF Vij, Ravi Kumar, Shaji Zhang, Mei-Jie Zhong, Xiaobo Huang, Jiaxing Dispenzieri, Angela Abidi, Muneer H. Bird, Jennifer M. Freytes, Cesar O. Gale, Robert Peter Kindwall-Keller, Tamila L. Kyle, Robert A. Landsburg, Daniel J. Lazarus, Hillard M. Munker, Reinhold Roy, Vivek Sharma, Manish Vogl, Dan T. Wirk, Baldeep Hari, Parameswaran N. TI Impact of Pretransplant Therapy and Depth of Disease Response before Autologous Transplantation for Multiple Myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Myeloma; Primary refractory; Autologous transplant ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; COMPLETE REMISSION; INTENSIVE THERAPY; CHEMOTHERAPY; SURVIVAL; INDUCTION; OUTCOMES; BENEFIT AB Patients with multiple myeloma (MM) who are eligible for autologous stem cell transplantation (ASCT) typically receive a finite period of initial therapy before ASCT. It is not clear if patients with suboptimal (less than a partial) response to initial therapy benefit from additional alternative therapy with intent to maximize pretransplant response. We identified 539 patients with MM who had an ASCT after having achieved less than a partial response (PR) to first-line induction chemotherapy between 1995 and 2010. These patients were then divided into 2 groups: those who received additional salvage chemotherapy before ASCT (n = 324) and those who had no additional salvage chemotherapy immediately before ASCT (n = 215). Additional pretransplant chemotherapy resulted in deepening responses in 68% (complete response in 8% and PR in 60%). On multivariate analysis there was no impact of pretransplant salvage chemotherapy on treatment-related mortality, risk for relapse, progression-free survival, or overall survival. In conclusion, for patients achieving less than a PR to initial induction therapy, including with novel agent combinations, additional pre-ASCT salvage chemotherapy improved the depth of response and pre-ASCT disease status but was not associated with survival benefit. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Vij, Ravi] Washington Univ, Sch Med, Div Hematol & Oncol, St Louis, MO USA. [Kumar, Shaji; Dispenzieri, Angela; Kyle, Robert A.] Mayo Clin, Dept Hematol, Rochester, MN USA. [Zhang, Mei-Jie; Zhong, Xiaobo; Huang, Jiaxing; Hari, Parameswaran N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Zhang, Mei-Jie] Inst Hlth & Soc, Div Biostat, Milwaukee, WI USA. [Abidi, Muneer H.] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Div BMT, Detroit, MI USA. [Bird, Jennifer M.] Univ Hosp Bristol NHS, Dept Haematol, Bristol, Avon, England. [Freytes, Cesar O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Hematol Res Ctr, Div Expt Med, London, England. [Kindwall-Keller, Tamila L.] Univ Virginia Hlth Syst, Div Hematol Oncol, Charlottesville, VA USA. [Landsburg, Daniel J.; Vogl, Dan T.] Univ Penn, Abramson Canc Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Munker, Reinhold] Louisiana State Univ Hlth Shreveport, Dept Internal Med, Div Hematol Oncol, Shreveport, LA USA. [Roy, Vivek] Mayo Clin, Blood & Marrow Transplant Program, Jacksonville, FL 32224 USA. [Sharma, Manish] Thomas Jefferson Univ, Dept Internal Med, Philadelphia, PA 19107 USA. [Wirk, Baldeep] SUNY Stony Brook, Med Ctr, Dept Internal Med, Stony Brook, NY 11794 USA. RP Hari, PN (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Div Hematol & Oncol, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu RI Kumar, Shaji/A-9853-2008; OI Kumar, Shaji/0000-0001-5392-9284; Abidi, Muneer/0000-0002-9936-6031; Hari, Parameswaran/0000-0002-8800-297X; Dispenzieri, Angela/0000-0001-8780-9512 FU National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI and NCI [5U10HL069294]; Health Resources and Services Administration [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Office of Naval Research; *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be The Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *Terumo BCT; *Teva Neuroscience, Inc.; *Therakos; University of Minnesota; University of Utah; WellPoint FX Financial disclosure: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; contract HHSH250201200016C with the Health Resources and Services Administration; 2 grants (N00014-12-1-0142 and N00014-13-1-0039) from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be The Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *Terumo BCT; *Teva Neuroscience, Inc.; *Therakos; University of Minnesota; University of Utah; and *WellPoint The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration; or any other agency of the U.S. Government. Asterisk (*) indicates corporate members. NR 19 TC 14 Z9 14 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 FEB PY 2015 VL 21 IS 2 BP 335 EP 341 DI 10.1016/j.bbmt.2014.10.023 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CA0UW UT WOS:000348632700019 PM 25445028 ER PT J AU Billen, A Madrigal, JA Strydom, A Szydlo, RM Switzer, GE Shaw, BE AF Billen, Annelies Madrigal, J. Alejandro Strydom, Andre Szydlo, Richard M. Switzer, Galen E. Shaw, Bronwen E. TI Predonation Health-Related Quality of Life Scores Predict Time to Recovery in Hematopoietic Stem Cell Donors SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Peripheral blood stem cells; Bone marrow; Donation experience; Health-related quality of life ID COLONY-STIMULATING FACTOR; UNRELATED BONE-MARROW; ADVERSE EVENTS; PROSPECTIVE TRIAL; FOLLOW-UP; BLOOD; DONATION; PAIN; DEPRESSION; EXPERIENCE AB The physical reactions to hematopoietic stem cell donation have been extensively studied, but less is known about factors that predict poorer donation experiences. The aim of this prospective study was to examine demographic and health-related quality of life (HRQOL) factors that might be associated with recovery and side effects. We also described the changes in HRQOL during the donation process. In total, 275 peripheral blood stem cell (PBSC) and 37 bone marrow (BM) consecutive donors completed the SF-36 questionnaire predonation and 4 weeks, and 3 months postdonation. Predonation HRQOL markers were the strongest predictors of time to recovery. Poorer predonation physical health was associated with longer recovery (P = .017) and certain side effects in PBSC donors. Poorer predonation mental health was associated with longer recovery in BM donors (P = .03) and pain after PBSC donation (P = .003). Physical HRQOL scores declined significantly from predonation to 4 weeks postdonation. This was shown both for PBSC and BM donors (P < .001 and P = .009, respectively), but the decline was much greater for BM donors. There was a return to predonation HRQOL values 3 months after donation in both groups with values well above the mean of the general population (P < .001). (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Billen, Annelies; Madrigal, J. Alejandro; Shaw, Bronwen E.] UCL, Inst Canc, London, England. [Billen, Annelies; Madrigal, J. Alejandro; Shaw, Bronwen E.] Anthony Nolan Res Inst, London, England. [Strydom, Andre] UCL, Mental Hlth Sci Unit, London, England. [Szydlo, Richard M.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England. [Switzer, Galen E.] Univ Pittsburgh, Dept Gen Internal Med, Pittsburgh, PA USA. [Switzer, Galen E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Shaw, Bronwen E.] Royal Marsden Hosp, Dept Haematol, London SW3 6JJ, England. RP Billen, A (reprint author), Anthony Nolan,2 Heathgate Pl,75-87 Agincourt Rd, London NW3 2N, England. EM Annelies.billen@anthonynolan.org RI Szydlo, Richard/C-6678-2012 OI Szydlo, Richard/0000-0003-1102-8298 NR 36 TC 3 Z9 4 U1 2 U2 4 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 FEB PY 2015 VL 21 IS 2 BP 350 EP 356 DI 10.1016/j.bbmt.2014.10.028 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CA0UW UT WOS:000348632700021 PM 25452034 ER PT J AU Bedair, H Yang, J Dwyer, MK McCarthy, JC AF Bedair, Hany Yang, Judy Dwyer, Maureen K. McCarthy, Joseph C. TI Preoperative Erythropoietin Alpha Reduces Postoperative Transfusions in THA and TKA but May Not Be Cost-effective SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL KNEE ARTHROPLASTY; PRIMARY TOTAL HIP; AUTOLOGOUS BLOOD-DONATION; TOTAL JOINT ARTHROPLASTY; RECOMBINANT-HUMAN-ERYTHROPOIETIN; TRANEXAMIC ACID; ORTHOPEDIC-SURGERY; EPOETIN-ALPHA; REPLACEMENT; TRIAL AB Preoperative erythropoietin alpha (EPO) has been shown to be effective at reducing postoperative blood transfusions in total hip arthroplasty (THA) and total knee arthroplasty (TKA); however, treatment with EPO is associated with additional costs, and it is not known whether these costs can be justified when weighed against the transfusion reductions achieved in patients who receive the drug. The purpose of this study is to investigate (1) efficacy of preoperative EPO in reducing postoperative transfusions in TKA and THA; (2) whether patients treated with EPO have reduced length of stay or a different discharge disposition; and (3) whether EPO use reduces overall blood management costs. Patients undergoing primary THA or TKA over a 10-month period with preoperative hemoglobin < 13 g/dL were recommended to be treated preoperatively with EPO. During that time, 80 of 286 (28%) patients met that inclusion criterion and the treating team recommended EPO to all of them; of that group, 24 (30%) opted to take EPO and 56 (70%) opted not to. Patients receiving at least one dose of EPO and those not receiving EPO were compared in terms of transfusion frequency, length of stay and discharge disposition, and overall blood management costs. Demographics, preoperative hemoglobin, and operative blood loss for both groups were similar (p > 0.05). No transfusion triggers were used; rather, patients with postoperative hemoglobin < 10 mg/dL and who were symptomatic despite fluid boluses were transfused. The clinician responsible for transfusing symptomatic patients was blinded to the patient's EPO treatment status. Costs were defined as direct costs paid or incurred by our institution for EPO, allogeneic blood, and variable costs associated with patient care after THA/TKA. A decision-tree cost analysis was performed using the collected clinical data and cost data collected from our institution; the analysis considered total associated blood management cost for an EPO and a non-EPO strategy with sensitivity analysis of key cost variables. The proportion of patients receiving transfusions was lower in patients who received EPO than in patients who did not (0% [zero of 24] versus 41% [23 of 56]; p < 0.001). The mean length of inpatient hospital stay (EPO: 3.0 +/- A 0.4 versus control: 3.3 +/- A 0.8 days, p = 0.77) and discharge disposition also was not different between the groups. The cost analysis demonstrated that the EPO strategy was more costly compared with no EPO (USD 2632 versus USD 2284) and its cost would need to be less than USD 225/dose for this to change. EPO reduced the need for postoperative transfusions in high-risk patients undergoing THA and TKA; however, it was not found to be cost-effective in our model. Our model could not consider relatively rare complications of blood transfusions, including disease transmission, deep periprosthetic infections, and transfusion reactions, but if surgeons or patients value avoiding these potential but rare factors highly, this could reasonably influence the decision of whether to use EPO despite our findings that it was not cost-effective. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Bedair, Hany; Dwyer, Maureen K.; McCarthy, Joseph C.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. [Bedair, Hany; Yang, Judy; Dwyer, Maureen K.; McCarthy, Joseph C.] Newton Wellesley Hosp, Kaplan Ctr Joint Reconstruct Surg, Newton, MA 02462 USA. RP Bedair, H (reprint author), Newton Wellesley Hosp, Kaplan Ctr Joint Reconstruct Surg, 2014 Washington St,Green Bldg,Suite 361, Newton, MA 02462 USA. EM hbedair@partners.org NR 39 TC 15 Z9 16 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 FEB PY 2015 VL 473 IS 2 BP 590 EP 596 DI 10.1007/s11999-014-3819-z PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AZ6QY UT WOS:000348344900035 PM 25106796 ER PT J AU Hansen, VJ Gromov, K Lebrun, LM Rubash, HE Malchau, H Freiberg, AA AF Hansen, Viktor J. Gromov, Kirill Lebrun, Lauren M. Rubash, Harry E. Malchau, Henrik Freiberg, Andrew A. TI Does the Risk Assessment and Prediction Tool Predict Discharge Disposition After Joint Replacement? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL KNEE REPLACEMENT; TOTAL HIP-ARTHROPLASTY; QUALITY-OF-LIFE; RESOURCE UTILIZATION; COST-EFFECTIVENESS AB Payers of health services and policymakers place a major focus on cost containment in health care. Studies have shown that early planning of discharge is essential in reducing length of stay and achieving financial benefit; tools that can help predict discharge disposition would therefore be of use. The Risk Assessment and Prediction Tool (RAPT) is a preoperative survey constructed to predict discharge disposition after total joint arthroplasty (TJA). The RAPT was developed and tested on a population of Australian patients undergoing joint replacement, but its validity in other populations is unknown. A low RAPT score is reported to indicate a high risk of needing any form of inpatient rehabilitation after TJA, including short-term nursing facilities. This study attempts (1) to assess predictive accuracy of the RAPT on US patients undergoing total hip and knee arthroplasty (THA/TKA); and (2) to determine predictive accuracy of each individual score (1-12). Between June 2006 and December 2011, RAPT scores of 3213 patients (1449 THAs; 1764 TKAs) were prospectively captured during the preoperative clinical visit. Scores were stored along with other clinical data, including discharge disposition, in a dedicated database on a secure server. The database was queried by the nursing case manager to retrieve the RAPT scores of all patients captured during this time period. Binary logistic regression was used to analyze the scores and determine predictive accuracy. Overall predictive accuracy was 78%. RAPT scores < 6 and > 10 (of 12) predicted with > 90% accuracy discharge to inpatient rehabilitation and home, respectively. Predictive accuracy was lowest for scores between 7 and 10 at 65.2% and almost 50% of patients received scores in this range. Based on our findings, the risk categories in our populations should be high risk < 7, intermediate risk 7 to 10, and low risk > 10. The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort. Based on our data, intermediate-risk patients should be defined as those with scores of 7 to 10. Predictive accuracy for these patients could potentially be improved through the identification and addition of other factors correlated to discharge disposition. The RAPT allows for identification of patients who are likely to be discharged home or to rehabilitation, which may facilitate preoperative planning of postoperative care. Additionally, it identifies intermediate-risk patients and could be used to implement targeted interventions to facilitate discharge home in this group of patients. Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. C1 [Hansen, Viktor J.; Gromov, Kirill; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Lebrun, Lauren M.; Rubash, Harry E.; Malchau, Henrik; Freiberg, Andrew A.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Gromov, Kirill] Copenhagen Univ Hosp, Dept Orthopaed Surg, Copenhagen, Denmark. RP Freiberg, AA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,Yawkey Suite 3B, Boston, MA 02114 USA. EM afreiberg@mgh.harvard.edu NR 16 TC 9 Z9 9 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 FEB PY 2015 VL 473 IS 2 BP 597 EP 601 DI 10.1007/s11999-014-3851-z PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AZ6QY UT WOS:000348344900036 PM 25106801 ER PT J AU Dwyer, MK Jones, HL Field, RE McCarthy, JC Noble, PC AF Dwyer, Maureen K. Jones, Hugh L. Field, Richard E. McCarthy, Joseph C. Noble, Philip C. TI Femoroacetabular Impingement Negates the Acetabular Labral Seal During Pivoting Maneuvers but Not Gait SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID FINITE-ELEMENT MODEL; HIP-JOINT; OSTEOARTHRITIS; MECHANICS; FEATURES; ANATOMY; DAMAGE; TEARS; MRI AB Experimental disruption of the labrum has been shown to compromise its sealing function and alter cartilage lubrication. However, it is not known whether pathological changes to the labrum secondary to femoroacetabular impingement (FAI) have a similar impact on labral function. Does damage to the labrum occurring in association with abnormal femoral morphology affect the labral seal? Using 10 fresh cadaveric specimens (mean age 50 years, +/- A 8), we measured the capacity of the central compartment of the hip (the iliofemoral joint) to maintain a seal during fluid infusion, which may help elucidate the function of the labrum during weightbearing. Specimens with and without abnormal femoral morphology (six normal-appearing specimens and four whose geometry suggested cam-type FAI) were tested in postures observed during functional activities, including simulations of normal gait, stooping, and pivoting. Each specimen with FAI morphology exhibited secondary damage of the labrum and the adjacent chondral surface, whereas specimens of normal morphology were undamaged. Average peak central compartment pressure was reduced during pivoting for specimens with the presence of labral damage secondary to FAI. When placed in pivoting positions, hips with FAI maintained lower fluid pressures within the central compartment compared with intact specimens (15 +/- A 3 versus 42 +/- A 8 kPa, respectively; effect size: 1.08 [-0.36 to 2.31]; p = 0.007). No differences in peak pressure were observed between groups (FAI versus normal) for postures simulating either gait (21 +/- A 6 versus 22 +/- A 4 kPa; p = 0.902) or stooping (9 +/- A 2 versus 8 +/- A 3 kPa; p = 0.775) with the numbers available. The acetabular seal, quantified by the maximum intraarticular pressure, was reduced during pivoting; however, the seal was maintained during simulated gait and stooping. Because degeneration is progressive with repetitive impingement, loss of the labral seal starts to be seen during pivoting and may progress from there, but in this small-sample cadaver study that evaluated specimens in middle adulthood, the seal remains intact during simulated gait and stooping. Our study suggests that labral damage secondary to cam-type FAI may reduce the ability of the labral to provide an adequate seal of the central compartment of the hip during loading; however, the extent to which this is affected requires further investigation. C1 [Dwyer, Maureen K.; McCarthy, Joseph C.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. [Dwyer, Maureen K.; McCarthy, Joseph C.] Newton Wellesley Hosp, Kaplan Joint Ctr, Newton, MA 02462 USA. [Jones, Hugh L.; Noble, Philip C.] Inst Orthoped Res & Educ, Houston, TX USA. [Field, Richard E.] St Anthony Hosp, Sutton, Surrey, England. [Noble, Philip C.] Baylor Coll Med, Houston, TX 77030 USA. RP Dwyer, MK (reprint author), Newton Wellesley Hosp, Kaplan Joint Ctr, 2000 Washington St,Green Bldg,Suite 361, Newton, MA 02462 USA. EM mkdwyer@partners.org NR 22 TC 3 Z9 3 U1 1 U2 1 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 FEB PY 2015 VL 473 IS 2 BP 602 EP 607 DI 10.1007/s11999-014-3760-1 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AZ6QY UT WOS:000348344900037 PM 24989124 ER PT J AU Hageman, MGJS Briet, JP Bossen, JK Blok, RD Ring, DC Vranceanu, AM AF Hageman, Michiel G. J. S. Briet, Jan Paul Bossen, Jeroen K. Blok, Robin D. Ring, David C. Vranceanu, Ana-Maria TI Do Previsit Expectations Correlate With Satisfaction of New Patients Presenting for Evaluation With an Orthopaedic Surgical Practice? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; PRIMARY-CARE; HEALTH-CARE; PREOPERATIVE EXPECTATIONS; GENERAL-PRACTICE; DETERMINANTS; CONSULTATIONS; POPULATION; PREDICTORS; SURGERY AB Patient satisfaction is associated with increased compliance, improved treatment outcomes, and decreased risk of litigation. Factors such as patient understanding and psychological well-being are recognized influences on satisfaction. Less is known about the relationship between previsit expectations and satisfaction. (1) Are there correlations among previsit expectations, met expectations, and patient satisfaction? (2) What are the categories of expectations, and which one(s) correlate with satisfaction? Eighty-six new patients presenting to a hand surgery practice of a tertiary referral hospital with 70% direct primary care referrals, mostly with elective concerns, indicated their previsit expectations (Patient Intention Questionnaire [PIQ]). Immediately after the visit, the same patients rated the degree to which their previsit expectations were met (Expectation Met Questionnaire [EMQ]) and their satisfaction level (Medical Interview Satisfaction Scale). These tools have been used in primary care office settings and claim good psychometric properties, and although they have not been strictly validated for responsiveness and other test parameters, they have good face validity. We then conducted a multivariable backward linear regression to determine whether (1) scores on the PIQ; and (2) scores on the EMQ are associated with satisfaction. Satisfaction correlated with met expectations (r = 0.36; p < 0.001) but not with previsit expectations (r = -0.01, p = 0.94). We identified five primary categories of previsit expectations that accounted for 50% of the variance in PIQ: (1) "Information and Explanation"; (2) "Emotional and Understanding"; (3) "Emotional Problems"; (4) "Diagnostics"; and (5) "Comforting". The only category of met expectations that correlated with satisfaction was Information and Explanation (r = 0.43; p < 0.001). Among patients seeing a hand surgeon, met expectations correlate with satisfaction. In particular, patients with met expectations regarding information and explanation were more satisfied with their visit. Efforts to determine the most effective methods for conveying unexpected information warrant investigation. Level II, prognostic study. C1 [Hageman, Michiel G. J. S.; Briet, Jan Paul; Bossen, Jeroen K.; Blok, Robin D.; Ring, David C.; Vranceanu, Ana-Maria] Harvard Univ, Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv,Med Sch, Boston, MA 02114 USA. RP Ring, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv,Med Sch, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM d.ring@mgh.harvard.edu OI Blok, Robin/0000-0002-5291-546X FU "Marti kuning Eckhardt fonds"; "Spinoza fonds"; "AnnaFonds Travel grant" (Dutch orthopaedic travel grant) FX One of the authors (MGJSH) was supported by "Marti kuning Eckhardt fonds," a nonmedical study grant, "Spinoza fonds," a nonmedical study grant, and a "AnnaFonds Travel grant" (Dutch orthopaedic travel grant). One of the authors (RDB) was supported by "Spinza fonds," a nonmedical study grant. NR 27 TC 4 Z9 4 U1 2 U2 7 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 FEB PY 2015 VL 473 IS 2 BP 716 EP 721 DI 10.1007/s11999-014-3970-6 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AZ6QY UT WOS:000348344900053 PM 25269531 ER PT J AU Teunis, T Nota, SPFT Schwab, JH AF Teunis, Teun Nota, Sjoerd P. F. T. Schwab, Joseph H. TI Do Corresponding Authors Take Responsibility for Their Work? A Covert Survey SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID AVAILABILITY; METAANALYSIS; SCIENCE; TRIALS AB Publication of a manuscript does not end an author's responsibilities. Reasons to contact an author after publication include clarification, access to raw data, and collaboration. However, legitimate questions have been raised regarding whether these responsibilities generally are being met by corresponding authors of biomedical publications. This study aims to establish (1) what proportion of corresponding authors accept the responsibility of correspondence; (2) identify characteristics of responders; and (3) assess email address decay with time. We hypothesize that the response rate is unrelated to journal impact factor. We contacted 450 corresponding authors throughout various fields of biomedical research regarding the availability of additional data from their study, under the pretense of needing these data for a related review article. Authors were randomly selected from 45 journals whose impact factors ranged from 52 to 0; the source articles were published between May 2003 and May 2013. The proportion of corresponding authors who replied, along with author characteristics were recorded, as was the proportion of emails that were returned for inactive addresses; 446 authors were available for final analysis. Fifty-three percent (190/357) of the authors with working email addresses responded to our request. Clinical researchers were more likely to reply than basic/translational scientists (51% [114/225] versus 34% [76/221]; p < 0.001). Impact factor and other author characteristics did not differ. Logistic regression analysis showed that the odds of replying decreased by 15% per year (odds ratio [OR], 0.85; 95% CI, 0.79-0.91; p < 0.001), and showed a positive relationship between clinical research and response (OR, 2.0; 95% CI, 1.3-2.9; p = 0.001). In 2013 all email addresses (45/45) were reachable, but within 10 years, 49% (21/43) had become invalid. Our results suggest that contacting corresponding authors is problematic throughout the field of biomedical research. Defining the responsibilities of corresponding authors by journals more explicitly-particularly after publication of their manuscript-may increase the response rate on data requests. Possible other ways to improve communication after research publication are: (1) listing more than one email address per corresponding author, eg, an institutional and personal address; (2) specifying all authors' email addresses; (3) when an author leaves an institution, send an automated reply offering alternative ways to get in touch; and (4) linking published manuscripts to research platforms. C1 [Teunis, Teun; Nota, Sjoerd P. F. T.] Harvard Univ, Dept Orthopaed Surg, Musculoskeletal Oncol Serv, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Schwab, Joseph H.] Harvard Univ, Dept Orthopaed Surg, Musculoskeletal Oncol Serv, Massachusetts Gen Hosp,Med Sch,Spine Surg Serv, Boston, MA 02114 USA. RP Teunis, T (reprint author), Harvard Univ, Dept Orthopaed Surg, Musculoskeletal Oncol Serv, Massachusetts Gen Hosp,Med Sch, Room 3-946,Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA. EM teunteunis@gmail.com FU Prince Bernhard Culture Fund; Kuitse Fung (Amsterdam, The Netherlands); Fundatie van de Vrijvrouwe van Renswoude te's-Gravenhage (The Hague, The Netherlands); Stryker (Kalamazoo, MI, USA); Biom'up (Saint-Priest, France) FX One of the authors (TT) received research grants from the Prince Bernhard Culture Fund & Kuitse Fung (Amsterdam, The Netherlands) (less than USD 10,000), and Fundatie van de Vrijvrouwe van Renswoude te's-Gravenhage (The Hague, The Netherlands) (less than USD 10,000).; One of the authors (JS) certifies that he, or a member of his immediate family, has or may receive payments or benefits, during the study period from Stryker (Kalamazoo, MI, USA) (less than USD 10,000), and Biom'up (Saint-Priest, France) (less than USD 10,000). NR 18 TC 4 Z9 4 U1 3 U2 7 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 FEB PY 2015 VL 473 IS 2 BP 729 EP 735 DI 10.1007/s11999-014-3868-3 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AZ6QY UT WOS:000348344900055 PM 25123243 ER PT J AU Dzhala, V Staley, KJ AF Dzhala, Volodymyr Staley, Kevin J. TI Acute and Chronic Efficacy of Bumetanide in an in vitro Model of Posttraumatic Epileptogenesis SO CNS Neuroscience & Therapeutics LA English DT Article DE Bumetanide; NKCC1; phenobarbital; posttraumatic seizures; Trauma ID CATION-CHLORIDE COTRANSPORTERS; TEMPORAL-LOBE EPILEPSY; K-CL COTRANSPORTER; NEONATAL SEIZURES; RAT HIPPOCAMPUS; NEURONAL COMMUNICATION; SYNAPTIC PLASTICITY; EXCITATORY ACTIONS; INTERICTAL SPIKES; DEVELOPING BRAIN AB BackgroundSeizures triggered by acute injuries to the developing brain respond poorly to first-line medications that target the inhibitory chloride-permeable GABA(A) receptor. Neuronal injury is associated with profound increases in cytoplasmic chloride ([Cl-](i)) resulting in depolarizing GABA signaling, higher seizure propensity and limited efficacy of GABAergic anticonvulsants. The Na+-K+-2Cl(-) (NKCC1) cotransporter blocker bumetanide reduces [Cl-](i) and causes more negative GABA equilibrium potential in injured neurons. We therefore tested both the acute and chronic efficacy of bumetanide on early posttraumatic ictal-like epileptiform discharges and epileptogenesis. MethodsAcute hippocampal slices were used as a model of severe traumatic brain injury and posttraumatic epileptogenesis. Hippocampal slices were then incubated for 3weeks. After a 1-week latent period, slice cultures developed chronic spontaneous ictal-like discharges. The anticonvulsant and anti-epileptogenic efficacy of bumetanide, phenobarbital, and the combination of these drugs was studied. ResultsBumetanide reduced the frequency and power of early posttraumatic ictal-like discharges in vitro and enhanced the anticonvulsant efficacy of phenobarbital. Continuous 2-3weeks administration of bumetanide as well as phenobarbital in combination with bumetanide failed to prevent posttraumatic ictal-like discharges and epileptogenesis. ConclusionsOur data demonstrate a persistent contribution of NKCC1 cotransport in posttraumatic ictal-like activity, presumably as a consequence of chronic alterations in neuronal chloride homeostasis and GABA-mediated inhibition. New strategies for more effective reduction in posttraumatic and seizure-induced [Cl-](i) accumulation could provide the basis for effective treatments for posttraumatic epileptogenesis and the resultant seizures. C1 [Dzhala, Volodymyr; Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Staley, KJ (reprint author), MGH Neurol, CNY 114,Room 2600,114 16th St, Charlestown, MA 02129 USA. EM staley.kevin@mgh.harvard.edu FU NIH (NINDS) [RO1 NS 40109-13] FX This study was supported by NIH grant RO1 NS 40109-13 (NINDS). We thank Michelle Mail for technical assistance. NR 55 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 EI 1755-5949 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PD FEB PY 2015 VL 21 IS 2 SI SI BP 173 EP 180 DI 10.1111/cns.12369 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CA3YL UT WOS:000348841000011 PM 25495911 ER PT J AU Barnard, LS Wexler, DJ DeWalt, D Berkowitz, SA AF Barnard, Lily S. Wexler, Deborah J. DeWalt, Darren Berkowitz, Seth A. TI Material Need Support Interventions for Diabetes Prevention and Control: a Systematic Review SO CURRENT DIABETES REPORTS LA English DT Article DE Diabetes mellitus; Social determinants of health; Food insecurity; Poverty; Housing instability; Diabetes mellitus/therapy; Socioeconomic status ID NUTRITION EXAMINATION SURVEY; FOOD INSECURITY; SOCIAL DETERMINANTS; CARDIOVASCULAR-DISEASE; MEDICATION UNDERUSE; SOCIOECONOMIC DISPARITIES; FINANCIAL INCENTIVES; AFRICAN-AMERICAN; GLYCEMIC CONTROL; SELF-MANAGEMENT AB Unmet material needs, such as food insecurity and housing instability, are associated with increased risk of diabetes and worse outcomes among diabetes patients. Healthcare delivery organizations are increasingly held accountable for health outcomes that may be related to these "social determinants," which are outside the scope of traditional medical intervention. This review summarizes the current literature regarding interventions that provide material support for income, food, housing, and other basic needs. In addition, we propose a conceptual model of the relationship between unmet needs and diabetes outcomes and provide recommendations for future interventional research. C1 [Barnard, Lily S.] Tufts Univ, Biol Program, Medford, MA 02155 USA. [Barnard, Lily S.] Tufts Univ, Community Hlth Program, Medford, MA 02155 USA. [Wexler, Deborah J.; Berkowitz, Seth A.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Wexler, Deborah J.; Berkowitz, Seth A.] Harvard Univ, Sch Med, Boston, MA USA. [DeWalt, Darren] Univ N Carolina, Div Gen Internal Med & Clin Epidemiol, Chapel Hill, NC USA. [Berkowitz, Seth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Berkowitz, SA (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM SABerkowitz@partners.org OI Berkowitz, Seth/0000-0003-1030-4297; DeWalt, Darren/0000-0003-2270-751X NR 70 TC 2 Z9 2 U1 4 U2 23 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD FEB PY 2015 VL 15 IS 2 AR 2 DI 10.1007/s11892-014-0574-1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CA3EJ UT WOS:000348788800006 ER PT J AU Buschur, E Brown, F Wyckoff, J AF Buschur, Elizabeth Brown, Florence Wyckoff, Jennifer TI Using Oral Agents to Manage Gestational Diabetes: What Have We Learned? SO CURRENT DIABETES REPORTS LA English DT Article DE Glyburide; Metformin; Pregnancy; Gestational diabetes; Oral agents ID HYPOGLYCEMIC AGENTS; CLINICAL-PRACTICE; PERINATAL OUTCOMES; PREGNANCY OUTCOMES; HUMAN PLACENTA; FETAL SAFETY; GLYBURIDE; INSULIN; METFORMIN; MELLITUS AB Insulin has been the mainstay of treatment of diabetes during pregnancy for decades. Although glyburide and metformin are classified as category B during pregnancy, recent research has suggested that these oral agents alone or in conjunction with insulin may be safe for the treatment of gestational diabetes (GDM). This paper summarizes the data on the use of glyburide and metformin for treatment of GDM. C1 [Buschur, Elizabeth; Wyckoff, Jennifer] Univ Michigan, Ann Arbor, MI 48105 USA. [Brown, Florence] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Wyckoff, J (reprint author), Univ Michigan, 24 Frank Lloyd Wright Dr, Ann Arbor, MI 48105 USA. EM eliosbor@med.umich.edu; Florence.brown@joslin.harvard.edu; jwyckoff@med.umich.edu NR 66 TC 0 Z9 0 U1 1 U2 5 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD FEB PY 2015 VL 15 IS 2 AR 4 DI 10.1007/s11892-014-0570-5 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CA3EJ UT WOS:000348788800002 ER PT J AU Satterthwaite, TD Baker, JT AF Satterthwaite, Theodore D. Baker, Justin T. TI How can studies of resting-state functional connectivity help us understand psychosis as a disorder of brain development? SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID BIPOLAR DISORDER; DEFAULT NETWORK; SCHIZOPHRENIA; ORGANIZATION; MOTION; DYSCONNECTIVITY; ARCHITECTURE; DYNAMICS; IMPACT; CORTEX AB Psychosis is increasingly being understood as a neurodevelopmental 'dysconnection' syndrome, in which neural connectivity at both microscopic and macroscopic levels of brain organization becomes disrupted during late adolescence and early adulthood. Tools to quantify normative brain development and identify individuals at risk are urgently needed to tailor appropriate strategies for prevention and intervention, and could substantially improve clinical outcomes. Resting-state functional connectivity magnetic resonance imaging (rsfc-MRI) provides a rich, functional description of the brain's macroscopic connectivity structure. Over the past several years, rsfc-MRI has evolved to be a powerful tool for studying both normal brain development and abnormalities associated with psychosis. Several recent advances highlight intriguing and potentially significant parallels between these two lines of research. For instance, rsfc-MRI work suggests that psychosis is accompanied by loss of segregation between large-scale brain association networks, a pattern that is normal in early life but typically matures into more segregated systems by young adulthood. Coupled with data sharing across large-scale neuroimaging studies, longitudinal assessments using rsfc-MRI in patients and those at risk will be essential for improving our biological understanding of psychosis and will help inform diagnosis, prognosis, and clinical decision-making. C1 [Satterthwaite, Theodore D.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Baker, Justin T.] McLean Hosp, Psychot Disorders Div, Belmont, MA 02178 USA. [Baker, Justin T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Satterthwaite, TD (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. EM sattertt@upenn.edu FU NIMH [K23MH098130, K23MH104515-01]; Marc Rapport Family Investigator grant through the Brain and Behavior Foundation; Maria Lorenz Pope Fellowship; [KL2 TR001100] FX TDS was supported by NIMH K23MH098130 and the Marc Rapport Family Investigator grant through the Brain and Behavior Foundation. JTB was supported by KL2 TR001100 (Harvard Catalyst), the Maria Lorenz Pope Fellowship, and NIMH K23MH104515-01. NR 50 TC 11 Z9 11 U1 3 U2 12 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD FEB PY 2015 VL 30 BP 85 EP 91 DI 10.1016/j.conb.2014.10.005 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AZ6OA UT WOS:000348337600013 PM 25464373 ER PT J AU Neale, BM Sklar, P AF Neale, Benjamin M. Sklar, Pamela TI Genetic analysis of schizophrenia and bipolar disorder reveals polygenicity but also suggests new directions for molecular interrogation SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; RARE CHROMOSOMAL DELETIONS; SCAN METAANALYSIS; HYPERACTIVITY DISORDER; ATTENTION-DEFICIT; HAPLOTYPE MAP; DUPLICATIONS; LOCI AB Over the last few years, genetics research has made significant strides in identifying many risk factors for schizophrenia and bipolar disorder. These risk factors include inherited common single nucleotide polymorphisms, copy number variants, and rare single nucleotide variants, as well as rare de novo variants. For all variants, the common theme has been that of polygenicity, meaning that many small genetic risk factors influence risk in the population and that no gene or variant on its own has been shown to be fully deterministic of schizophrenia or bipolar. When taken together, biological themes that have emerged including the importance of synaptic function and calcium signaling. This has implications for our understanding of the biological underpinnings of these diseases. C1 [Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Neale, Benjamin M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Neale, Benjamin M.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Neale, Benjamin M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Sklar, Pamela] Icahn Sch Med Mt Sinai, Div Psychiat Genom, Dept Psychiat, New York, NY 10029 USA. RP Neale, BM (reprint author), Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. EM bneale@broadinstitute.org; pamela.sklar@mssm.edu NR 62 TC 23 Z9 23 U1 5 U2 18 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD FEB PY 2015 VL 30 BP 131 EP 138 DI 10.1016/j.conb.2014.12.001 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AZ6OA UT WOS:000348337600019 PM 25544106 ER PT J AU Sosenko, JM Skyler, JS DiMeglio, LA Beam, CA Krischer, JP Greenbaum, CJ Boulware, D Rafkin, LE Matheson, D Herold, KC Mahon, J Palmer, JP AF Sosenko, Jay M. Skyler, Jay S. DiMeglio, Linda A. Beam, Craig A. Krischer, Jeffrey P. Greenbaum, Carla J. Boulware, David Rafkin, Lisa E. Matheson, Della Herold, Kevan C. Mahon, Jeffrey Palmer, Jerry P. CA Type 1 Diabet TrialNet Diabet Prevention Trial-Type 1 TI A New Approach for Diagnosing Type 1 Diabetes in Autoantibody-Positive Individuals Based on Prediction and Natural History SO DIABETES CARE LA English DT Article ID TRIAL-TYPE 1; IMPAIRED GLUCOSE-TOLERANCE; RISK SCORE; PREVENTION TRIAL-TYPE-1; INSULIN-RESISTANCE; MELLITUS; PARTICIPANTS; PROGRESSION; CHILDREN; PUBERTY AB OBJECTIVEWe assessed whether type 1 diabetes (T1D) can be diagnosed earlier using a new approach based on prediction and natural history in autoantibody-positive individuals.RESEARCH DESIGN AND METHODSDiabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Natural History Study (TNNHS) participants were studied. A metabolic index, the T1D Diagnostic Index60 (Index60), was developed from 2-h oral glucose tolerance tests (OGTTs) using the log fasting C-peptide, 60-min C-peptide, and 60-min glucose. OGTTs with Index60 2.00 and 2-h glucose <200 mg/dL (Ind60+Only) were compared with Index60 <2.00 and 2-h glucose 200 mg/dL (2hglu+Only) OGTTs as criteria for T1D. Individuals were assessed for C-peptide loss from the first Ind60+Only OGTT to diagnosis.RESULTSAreas under receiver operating characteristic curves were significantly higher for Index60 than for the 2-h glucose (P < 0.001 for both DPT-1 and the TNNHS). As a diagnostic criterion, sensitivity was higher for Ind60+Only than for 2hglu+Only (0.44 vs. 0.15 in DPT-1; 0.26 vs. 0.17 in the TNNHS) OGTTs. Specificity was somewhat higher for 2hglu+Only OGTTs in DPT-1 (0.97 vs. 0.91) but equivalent in the TNNHS (0.98 for both). Positive and negative predictive values were higher for Ind60+Only OGTTs in both studies. Postchallenge C-peptide levels declined significantly at each OGTT time point from the first Ind60+Only OGTT to the time of standard diagnosis (range -22 to -34% in DPT-1 and -14 to -27% in the TNNHS). C-peptide and glucose patterns differed markedly between Ind60+Only and 2hglu+Only OGTTs.CONCLUSIONSAn approach based on prediction and natural history appears to have utility for diagnosing T1D. C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa E.; Matheson, Della] Univ Miami, Div Endocrinol, Miami, FL 33132 USA. [DiMeglio, Linda A.] Indiana Univ, Sect Pediat Endocrinol Diabetol, Indianapolis, IN 46204 USA. [Beam, Craig A.] Western Michigan Univ, Sch Med, Div Epidemiol & Biostat, Kalamazoo, MI 49008 USA. [Krischer, Jeffrey P.; Boulware, David] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Greenbaum, Carla J.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. [Herold, Kevan C.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Palmer, Jerry P.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Endocrinol Metab & Nutr, Seattle, WA 98195 USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL 33132 USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016; OI DiMeglio, Linda/0000-0002-8033-6078 FU National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Center for Research Resources; JDRF; American Diabetes Association FX This work was funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Center for Research Resources, JDRF, and the American Diabetes Association. NR 16 TC 8 Z9 8 U1 0 U2 8 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 FEB PY 2015 VL 38 IS 2 BP 271 EP 276 DI 10.2337/dc14-1813 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AZ8JK UT WOS:000348461400027 PM 25519451 ER PT J AU Rasbach, L Jenkins, C Laffel, L AF Rasbach, Lisa Jenkins, Carolyn Laffel, Lori TI An Integrative Review of Self-efficacy Measurement Instruments in Youth With Type 1 Diabetes SO DIABETES EDUCATOR LA English DT Article ID SCHOOL-AGE-CHILDREN; GLYCEMIC CONTROL; HEALTH-PROMOTION; EMERGING ADULTS; ADOLESCENTS; MANAGEMENT; MELLITUS; OUTCOMES; BEHAVIORS; ADHERENCE AB Purpose The purpose of this study is to assess the extant literature on instruments used to measure self-efficacy in youth with type 1 diabetes (T1DM) and their caregivers and to critically evaluate these measurements. Methods An integrative review (2003-2013) was conducted searching PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and US National Library of Medicine PubMed service (PubMed) databases using key words diabetes, type 1 diabetes, and self-efficacy. The authors reviewed the resulting 294 references for inclusion criteria of (a) sample of youth with T1DM or sample of caregivers of youth with T1DM, (b) description of the self-efficacy instrument as primary research, and (c) the instrument measured self-efficacy specifically related to diabetes management. Forty-five articles out of the initial 294 met criteria. Results Of the 45 articles, 10 different self-efficacy instruments were identified. The primary theoretical framework used was Bandura's social cognitive theory and model of self-efficacy. Most participants were white middle-class T1DM youth. Evaluations to assess validity often were not reported; however, a majority of studies reported high internal consistency of the instruments. Conclusions Sample homogeneity could limit the applicability of results to certain patient populations. Further psychometric analysis, including validity assessments, should be conducted in more diverse samples. Development of valid and reliable instruments for measuring self-efficacy that are sensitive to change across a wider caregiver base over time is necessary. While this review examined reliable and valid instruments used in research, future opportunities include evaluation of measuring self-efficacy in T1DM youth exposed to recent advances in diabetes management technologies. C1 [Rasbach, Lisa; Jenkins, Carolyn] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Rasbach, Lisa; Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Rasbach, L (reprint author), Med Univ S Carolina, Coll Nursing, 99 Jonathan Lucas St,MSC 160, Charleston, SC 29425 USA. EM greenli@musc.edu FU NIH [P30DK036836] FX This research was supported by the NIH grant P30DK036836. The content is solely the responsibility of the authors and does not represent the official view of this organization. NR 75 TC 3 Z9 3 U1 3 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 EI 1554-6063 J9 DIABETES EDUCATOR JI Diabetes Educ. PD FEB PY 2015 VL 41 IS 1 BP 43 EP 58 DI 10.1177/0145721714550254 PG 16 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA AZ9IL UT WOS:000348527000004 PM 25216655 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Environmental Risk Factors for Inflammatory Bowel Diseases: A Review SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE Crohn's disease; Ulcerative colitis; Environment; Smoking; Diet; Vitamin D ID ARYL-HYDROCARBON RECEPTOR; AMBIENT AIR-POLLUTION; 25-HYDROXY VITAMIN-D; CROHNS-DISEASE; ULCERATIVE-COLITIS; CLOSTRIDIUM-DIFFICILE; PSYCHOLOGICAL STRESS; CIGARETTE-SMOKING; REDUCED RISK; DIETARY-FAT AB Inflammatory bowel diseases comprising Crohn's disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases. The key mechanism underlying the pathogenesis of these diseases is a dysregulated immune response to commensal flora in a genetically susceptible host. Thus intestinal microbial dysbiosis, host genetics, and the external environment all play an important role in the development of incident disease and in determining subsequent disease behavior and outcomes. There are several well-defined or putative environmental risk factors including cigarette smoking, appendectomy, diet, stress and depression, vitamin D as well as hormonal influence. The effect of some of the risk factors appears to differ between CD and UC suggesting that despite shared genetic and immunologic mechanisms, distinct pathways of pathogenesis exist. There is a growing body of literature identifying risk factors for incident disease. There is less rigorous literature defining triggers of relapse, and few controlled clinical trials examining if modification of such risk factors results in an improvement in patient outcomes. This is an area of considerable patient, physician, and scientific interest, and there is an important unmet need for rigorous studies of the external environment in disease pathogenesis and subsequent course. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU US National Institutes of Health [K23 DK097142] FX A.N.A is supported by funding from the US National Institutes of Health (K23 DK097142). NR 112 TC 19 Z9 20 U1 5 U2 37 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2015 VL 60 IS 2 BP 290 EP 298 DI 10.1007/s10620-014-3350-9 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ7SP UT WOS:000348418400004 PM 25204669 ER PT J AU Wright, AP Desai, AP Bajpai, S King, LY Sahani, DV Corey, KE AF Wright, Andrew P. Desai, Amit P. Bajpai, Surabhi King, Lindsay Y. Sahani, Dushyant V. Corey, Kathleen E. TI Gaps in Recognition and Evaluation of Incidentally Identified Hepatic Steatosis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Fatty liver; Primary care; Nonalcoholic steatohepatitis; CT scan; Imaging; Steatosis ID FATTY LIVER-DISEASE; FIBROSIS; SYSTEMS AB Nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease, is frequently diagnosed incidentally on imaging. The goal of the present study was to characterize rates of documentation and evaluation of incidentally identified steatosis. Adults who underwent abdominal computed tomography with incidentally reported steatosis from January 2008 to October 2011 and with a parts per thousand yen1 primary care appointment within 14 months following imaging were included. One hundred twenty-seven individuals with newly identified steatosis on imaging were included. Medical record documentation of newly identified steatosis occurred in only 29 individuals (22.8 %). Mention of steatosis within the "impression" section of radiology reports in addition to the report body was associated with significantly higher likelihood of primary care documentation (p = 0.007). Primary care documentation of steatosis was associated higher rates of evaluation for the etiology of steatosis include testing of aminotransferase levels (96.5 vs. 77.5 %, p = 0.025), alcohol use screening (89.6 vs. 66.3 %, p = 0.02), and hepatitis C screening (20.6 vs. 2.0 %, p = 0.002). No patient had documentation of the NAFLD fibrosis score and none were referred for specialist evaluation or for liver biopsy. However, when calculated, the NAFLD fibrosis score identified 14 patients (11 %) as high risk for advanced hepatic fibrosis. Documentation of incidentally identified steatosis is infrequent but was improved when steatosis was mentioned in the "impression" of radiographic reports. Documentation of steatosis was associated with increased rates of aminotransferase testing and alcohol use and hepatitis C screening. An important proportion of individuals with incidentally identified steatosis are at high risk of fibrosis and may benefit from additional evaluation. C1 [Wright, Andrew P.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Wright, Andrew P.; Bajpai, Surabhi; King, Lindsay Y.; Sahani, Dushyant V.; Corey, Kathleen E.] Harvard Univ, Sch Med, Boston, MA USA. [Desai, Amit P.] New York Presbyterian Hosp, Dept Gastroenterol & Hepatol, New York, NY USA. [Bajpai, Surabhi; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [King, Lindsay Y.; Corey, Kathleen E.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. RP Corey, KE (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM apwright@partners.org; apd9006@nyp.org; sbajpai@partners.org; lyking@partners.org; dsahani@partners.org; kcorey@partners.org FU NIK [K23DK 099422-0] FX K.E.C. receives funding from NIK K23DK 099422-0. NR 8 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2015 VL 60 IS 2 BP 333 EP 338 DI 10.1007/s10620-014-3346-5 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ7SP UT WOS:000348418400009 PM 25190263 ER PT J AU Ananthakrishnan, AN Cheng, A Cagan, A Cai, TX Gainer, VS Shaw, SY Churchill, S Karlson, EW Murphy, SN Kohane, I Liao, KP AF Ananthakrishnan, Ashwin N. Cheng, Alice Cagan, Andrew Cai, Tianxi Gainer, Vivian S. Shaw, Stanley Y. Churchill, Susanne Karlson, Elizabeth W. Murphy, Shawn N. Kohane, Isaac Liao, Katherine P. TI Mode of Childbirth and Long-Term Outcomes in Women with Inflammatory Bowel Diseases SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Crohn's disease; Ulcerative colitis; Pregnancy; Delivery; Caesarean section ID PREGNANCY-RELATED ISSUES; PERIANAL CROHNS-DISEASE; 25-HYDROXY VITAMIN-D; INCREASED RISK; DELIVERY; SAFETY; COHORT; IMPACT; EPIDEMIOLOGY; SURGERY AB Inflammatory bowel diseases [IBD; Crohn's disease (CD), ulcerative colitis] often affect women in their reproductive years. Few studies have analyzed the impact of mode of childbirth on long-term IBD outcomes. We used a multi-institutional IBD cohort to identify all women in the reproductive age-group with a diagnosis of IBD prior to pregnancy. We identified the occurrence of a new diagnosis code for perianal complications, IBD-related hospitalization and surgery, and initiation of medical therapy after either a vaginal delivery or caesarean section (CS). Cox proportional hazards models adjusting for potential confounders were used to estimate independent effect of mode of childbirth on IBD outcomes. Our cohort included 360 women with IBD (161 CS). Women in the CS group were likely to be older and more likely to have complicated disease behavior prior to pregnancy. During follow-up, there was no difference in the likelihood of IBD-related surgery (multivariate hazard ratio 1.75, 95 % confidence interval (CI) 0.40-7.75), IBD-related hospitalization (HR 1.39), initiation of immunomodulator therapy (HR 1.45), or anti-TNF therapy (HR 1.11). Among the 133 CD pregnancies with no prior perianal disease, we found no excess risk of subsequent new diagnosis perianal fistulae with vaginal delivery compared to CS (HR 0.19, 95 % CI 0.04-1.05). Mode of delivery did not influence natural history of IBD. In our cohort, vaginal delivery was not associated with increased risk of subsequent perianal disease in women with CD. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Shaw, Stanley Y.; Karlson, Elizabeth W.; Murphy, Shawn N.; Kohane, Isaac; Liao, Katherine P.] Harvard Univ, Sch Med, Boston, MA USA. [Cheng, Alice; Shaw, Stanley Y.; Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Cagan, Andrew; Gainer, Vivian S.] Partners HealthCare, Res IS & Comp, Charlestown, MA USA. [Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Churchill, Susanne; Murphy, Shawn N.; Kohane, Isaac] Brigham & Womens Hosp, Natl Ctr Biomed Comp I2b2, Boston, MA 02115 USA. [Karlson, Elizabeth W.; Liao, Katherine P.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kohane, Isaac] Childrens Hosp, Boston, MA 02115 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU NIH [U54LM008748, K08 AR060257, K24 AR052403, P60 AR047782, R01 AR049880]; American Gastroenterological Association; US National Institutes of Health [K23 DK097142]; Harold and Duval Bowen Fund FX The study was supported by NIH U54LM008748. A.N.A is supported by funding from the American Gastroenterological Association and from the US National Institutes of Health (K23 DK097142). K.P.L. is supported by NIH K08 AR060257 and the Harold and Duval Bowen Fund. E.W.K is supported by grants from the NIH (K24 AR052403, P60 AR047782, R01 AR049880). NR 35 TC 4 Z9 4 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2015 VL 60 IS 2 BP 471 EP 477 DI 10.1007/s10620-014-3353-6 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ7SP UT WOS:000348418400026 PM 25213079 ER PT J AU Borck, G Hog, F Dentici, ML Tan, PL Sowada, N Medeira, A Gueneau, L Thiele, H Kousi, M Lepri, F Wenzeck, L Blumenthal, I Radicioni, A Schwarzenberg, TL Mandriani, B Fischetto, R Morris-Rosendahl, DJ Altmuller, J Reymond, A Nurnberg, P Merla, G Dallapiccola, B Katsanis, N Cramer, P Kubisch, C AF Borck, Guntram Hog, Friederike Dentici, Maria Lisa Tan, Perciliz L. Sowada, Nadine Medeira, Ana Gueneau, Lucie Thiele, Holger Kousi, Maria Lepri, Francesca Wenzeck, Larissa Blumenthal, Ian Radicioni, Antonio Schwarzenberg, Tito Livio Mandriani, Barbara Fischetto, Rita Morris-Rosendahl, Deborah J. Altmuller, Janine Reymond, Alexandre Nurnberg, Peter Merla, Giuseppe Dallapiccola, Bruno Katsanis, Nicholas Cramer, Patrick Kubisch, Christian TI BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies SO GENOME RESEARCH LA English DT Article ID TATA-BINDING PROTEIN; COPY-NUMBER VARIANT; INTELLECTUAL DISABILITY; POL III; HYPOMYELINATING LEUKODYSTROPHY; PONTOCEREBELLAR HYPOPLASIA; PREINITIATION COMPLEX; INITIATION COMPLEX; TFIIB; PROMOTERS AB RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to regulate protein synthesis. Dysregulation of Pol III transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or tRNA processing factors cause neurogenetic disorders in humans, such as hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic missense alterations of BRF1 in three families. In support of the pathogenic potential of the discovered alleles, suppression or CRISPR-mediated deletion of bif1 in zebraflsh embryos recapitulated key neurodevelopmental phenotypes; in vivo complementation showed all four candidate mutations to be pathogenic in an apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce Pol III-related transcription activity in vitro. Taken together, our data show that BRF1 mutations that reduce protein activity cause neurodevelopmental anomalies, suggesting that BRF1-mediated Pol III transcription is required for normal cerebellar and cognitive development. C1 [Borck, Guntram; Sowada, Nadine; Kubisch, Christian] Univ Ulm, Inst Human Genet, D-89081 Ulm, Germany. [Hog, Friederike; Wenzeck, Larissa] Univ Munich, Gene Ctr Munich, D-81377 Munich, Germany. [Hog, Friederike; Wenzeck, Larissa] Univ Munich, Dept Biochem, Ctr Integrated Prot Sci CIPSM, D-81377 Munich, Germany. [Dentici, Maria Lisa; Lepri, Francesca; Dallapiccola, Bruno] Bambino Gesu Pediat Hosp, IRCCS, I-00165 Rome, Italy. [Tan, Perciliz L.; Kousi, Maria; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Medeira, Ana] CHLN, Hosp S Maria, Dept Pediat, Serv Genet, P-1649035 Lisbon, Portugal. [Gueneau, Lucie; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland. [Thiele, Holger; Altmuller, Janine; Nurnberg, Peter] Univ Cologne, CCG, D-50931 Cologne, Germany. [Blumenthal, Ian] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Blumenthal, Ian] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Radicioni, Antonio] Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy. [Schwarzenberg, Tito Livio] Univ Roma La Sapienza, Dept Neonatol, I-00161 Rome, Italy. [Mandriani, Barbara; Merla, Giuseppe] IRCCS Casa Sollievo Sofferenza, Med Genet Unit, I-71013 San Giovanni Rotondo, Italy. [Mandriani, Barbara] Univ Brescia, PhD Program, I-25121 Brescia, Italy. [Fischetto, Rita] AOU Policlin Consorziale, UO Malattie Metabol PO Giovanni 23, I-70120 Bari, Italy. [Morris-Rosendahl, Deborah J.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England. [Altmuller, Janine] Univ Cologne, Inst Human Genet, D-50931 Cologne, Germany. [Nurnberg, Peter] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany. [Nurnberg, Peter] Univ Cologne, CMMC, D-50931 Cologne, Germany. [Cramer, Patrick] Max Planck Inst Biophys Chem, Dept Mol Biol, D-37077 Gottingen, Germany. [Kubisch, Christian] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, D-20246 Hamburg, Germany. RP Borck, G (reprint author), Univ Ulm, Inst Human Genet, D-89081 Ulm, Germany. EM guntram.borck@uni-ulm.de RI Kubisch, Christian/F-1893-2011; Borck, Guntram/F-1868-2015; Dallapiccola, Bruno/K-8692-2016 OI Kubisch, Christian/0000-0003-4220-0978; Lepri, Francesca Romana/0000-0001-5331-0473; Katsanis, Nicholas/0000-0002-2480-0171; Dallapiccola, Bruno/0000-0002-5031-1013 FU Elite Network Bavaria program "Protein Dynamics in Health and Disease"; Deutsche Forschungsgemeinschaft [SFB646, GraKo1721, SFB960, SFB1064]; European Research Council; Jung-Stiftung; Vallee Foundation; Deutsche Forschungsgemeinschaft; Italian Ministry of Health; Lithuanian-Swiss Cooperation Program FX We thank the families for their collaboration. The clinical information and the patient pictures were uploaded to the web-based Dysmorphology Diagnostic System (DDS) developed by DYSCERNE-a European Network of Centres of Expertise for Dysmorphology (EU DG Sanco) and discussed among the DDS expert panel. We thank Sarah Sainsbury for mapping the BRF1 mutations on the hTFIIB structure; Karl Bertram and All A. Alfaiz for help with cloning and bioinformatic analyses; Bernd Lapatki and Leopoldo Zelante for discussions on clinical (including dental) aspects of the disorder; Birgit Budde, Dagmar Wieczorek, and Hilde van Esch for providing DNA; and Christelle Golzio and Michael Talkowski for zebrafish RNA-seq data. F.H. was supported by the Elite Network Bavaria program "Protein Dynamics in Health and Disease"; P.C. by the Deutsche Forschungsgemeinschaft (SFB646, GraKo1721, SFB960, SFB1064, CIPSM, NIM), an Advanced Grant of the European Research Council, the Jung-Stiftung, and the Vallee Foundation; G.B. by the Deutsche Forschungsgemeinschaft; G.M. by a grant from the Italian Ministry of Health (Ricerca Corrente 2012-14); and A.R. by the Lithuanian-Swiss Cooperation Program. NR 56 TC 15 Z9 16 U1 1 U2 14 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 FEB PY 2015 VL 25 IS 2 BP 155 EP 166 DI 10.1101/gr.176925.114 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CA5UY UT WOS:000348974500001 PM 25561519 ER PT J AU Malik, WQ Hochberg, LR Donoghue, JP Brown, EN AF Malik, Wasim Q. Hochberg, Leigh R. Donoghue, John P. Brown, Emery N. TI Modulation Depth Estimation and Variable Selection in State-Space Models for Neural Interfaces SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Brain-computer interface (BCI); brain-machine interface (BMI); feature selection; modulation depth (MD); neural decoding; neural interface; state-spacemodel; tetraplegia; variable selection ID PRIMARY MOTOR CORTEX; CORTICAL-NEURONS; INFORMATION; TETRAPLEGIA; GRASP; REACH; POPULATIONS; KINEMATICS; PREDICTION; ENSEMBLES AB Rapid developments in neural interface technology are making it possible to record increasingly large signal sets of neural activity. Various factors such as asymmetrical information distribution and across-channel redundancy may, however, limit the benefit of high-dimensional signal sets, and the increased computational complexity may not yield corresponding improvement in system performance. High-dimensional system models may also lead to overfitting and lack of generalizability. To address these issues, we present a generalized modulation depth measure using the state-space framework that quantifies the tuning of a neural signal channel to relevant behavioral covariates. For a dynamical system, we develop computationally efficient procedures for estimating modulation depth from multivariate data. We show that this measure can be used to rank neural signals and select an optimal channel subset for inclusion in the neural decoding algorithm. We present a scheme for choosing the optimal subset based on model order selection criteria. We apply this method to neuronal ensemble spike-rate decoding in neural interfaces, using our framework to relate motor cortical activity with intended movement kinematics. With offline analysis of intracortical motor imagery data obtained from individuals with tetraplegia using the BrainGate neural interface, we demonstrate that our variable selection scheme is useful for identifying and ranking the most information-rich neural signals. We demonstrate that our approach offers several orders of magnitude lower complexity but virtually identical decoding performance compared to greedy search and other selection schemes. Our statistical analysis shows that the modulation depth of human motor cortical single-unit signals is well characterized by the generalized Pareto distribution. Our variable selection scheme has wide applicability in problems involving multisensor signal modeling and estimation in biomedical engineering systems. C1 [Malik, Wasim Q.; Brown, Emery N.] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Malik, Wasim Q.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Malik, Wasim Q.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Malik, Wasim Q.; Hochberg, Leigh R.; Donoghue, John P.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Malik, Wasim Q.; Hochberg, Leigh R.; Donoghue, John P.] Dept Vet Affairs Med Ctr, Ctr Neurorestorat & Neurotechnol, Rehabil R&D Serv, Providence, RI 02908 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Malik, WQ (reprint author), Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM wmalik@mgh.harvard.edu; leigh_hochberg@brown.edu; john_donoghue@brown.edu; enb@neurostat.mit.edu OI Hochberg, Leigh/0000-0003-0261-2273 FU Department of Defense [W81XWH-09-2-0001]; Department of Veterans Affairs [B6453R, A6779I, B6310N, B6459L]; National Institutes of Health [R01 DC009899, RC1 HD063931, N01 HD053403, DP1 OD003646, TR01 GM104948]; National Science Foundation [CBET 1159652]; Wings for Life Spinal Cord Research Foundation; Doris Duke Foundation; MGH Neurological Clinical Research Institute; MGH Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; Cyberkinetics Neurotechnology Systems FX This work was supported in part by the Department of Defense (USAMRAA Cooperative Agreement W81XWH-09-2-0001), Department of Veterans Affairs (B6453R, A6779I, B6310N, and B6459L), National Institutes of Health (R01 DC009899, RC1 HD063931, N01 HD053403, DP1 OD003646, TR01 GM104948), National Science Foundation (CBET 1159652), Wings for Life Spinal Cord Research Foundation, Doris Duke Foundation, MGH Neurological Clinical Research Institute, and MGH Deane Institute for Integrated Research on Atrial Fibrillation and Stroke. The pilot clinical trial, in which participant S3 was recruited, was sponsored in part by Cyberkinetics Neurotechnology Systems. The BrainGate clinical trial is directed by Massachusetts General Hospital. The contents do not necessarily represent the views of the Department of Defense, Department of Veterans Affairs, or the United States Government. NR 40 TC 1 Z9 1 U1 2 U2 12 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 EI 1558-2531 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD FEB PY 2015 VL 62 IS 2 BP 570 EP 581 DI 10.1109/TBME.2014.2360393 PG 12 WC Engineering, Biomedical SC Engineering GA AZ5ZK UT WOS:000348297000019 PM 25265627 ER PT J AU Cai, WL Lee, JG Zhang, D Kim, SH Zalis, M Yoshida, H AF Cai, Wenli Lee, June-Goo Zhang, Da Kim, Se Hyung Zalis, Michael Yoshida, Hiroyuki TI Electronic Cleansing in Fecal-Tagging Dual-Energy CT Colonography Based on Material Decomposition and Virtual Colon Tagging SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Dual-energy CT (DE-CT); electronic cleansing (EC); partial volume effect (PVE); virtual colonoscopy ID COMPUTED-TOMOGRAPHY COLONOGRAPHY; AIDED POLYP DETECTION; CATHARTIC PREPARATION; SEGMENTATION; COLONOSCOPY; RECONSTRUCTION; FEASIBILITY; EXPERIENCE; LUMEN; AIR AB Dual-energy CT provides a promising solution to identify tagged fecal materials in electronic cleansing (EC) for fecal-tagging CT colonography (CTC). In this study, we developed a new EC method based on virtual colon tagging (VCT) for minimizing EC artifacts by use of the material decomposition ability in dual-energy CTC images. In our approach, a localized three-material decomposition model decomposes each voxel into a material mixture vector and the first partial derivatives of three base materials: luminal air, soft tissue, and iodine-tagged fecal material. A Poisson-based derivative smoothing algorithm smoothes the derivatives and implicitly smoothes the associated material mixture fields. VCT is a means for marking the entire colonic lumen by virtually elevating the CT value of luminal air as high as that of the tagged fecal materials to differentiate effectively soft-tissue structures from air tagging mixtures. Adual-energy EC scheme based on VCT method, denoted as VCT-EC, was developed, in which the colonic lumen was first virtually tagged and then segmented by its high values in VCT images. The performance of the VCT-EC scheme was evaluated in a phantom study and a clinical study. Our results demonstrated that our VCT-EC scheme may provide a significant reduction of EC artifacts. C1 [Cai, Wenli; Zhang, Da; Zalis, Michael; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli; Zhang, Da; Zalis, Michael; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lee, June-Goo] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Kim, Se Hyung] Seoul Natl Univ, Dept Radiol, Hosp Coll Med, Seoul 110744, South Korea. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM cai.wenli@mgh.harvard.edu; junegoo.lee@gmail.com; zhangda82@gmail.com; shkim@radcom.snu.ac.kr; mzalis@mgh.harvard.edu; yoshida.hiro@mgh.harvard.edu FU American Cancer Society [RSG-11-076-01-CCE] FX This work was supported by Research Scholar Grant RSG-11-076-01-CCE from the American Cancer Society. Asterisk indicates corresponding author. NR 43 TC 2 Z9 2 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 EI 1558-2531 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD FEB PY 2015 VL 62 IS 2 BP 754 EP 765 DI 10.1109/TBME.2014.2364837 PG 12 WC Engineering, Biomedical SC Engineering GA AZ5ZK UT WOS:000348297000038 PM 25350911 ER PT J AU Woo, J Stone, M Prince, JL AF Woo, Jonghye Stone, Maureen Prince, Jerry L. TI Multimodal Registration via Mutual Information Incorporating Geometric and Spatial Context SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article DE Multimodal image registration; mutual information; Harris operator ID FREE-FORM DEFORMATIONS; IMAGE REGISTRATION; NONRIGID REGISTRATION; TEMPORAL REGISTRATION; MAXIMIZATION; MR; VISUALIZATION; OPTIMIZATION; REGIONS; MOTION AB Multimodal image registration is a class of algorithms to find correspondence from different modalities. Since different modalities do not exhibit the same characteristics, finding accurate correspondence still remains a challenge. To deal with this, mutual information (MI)-based registration has been a preferred choice as MI is based on the statistical relationship between both volumes to be registered. However, MI has some limitations. First, MI-based registration often fails when there are local intensity variations in the volumes. Second, MI only considers the statistical intensity relationships between both volumes and ignores the spatial and geometric information about the voxel. In this work, we propose to address these limitations by incorporating spatial and geometric information via a 3D Harris operator. In particular, we focus on the registration between a high-resolution image and a low-resolution image. The MI cost function is computed in the regions where there are large spatial variations such as corner or edge. In addition, the MI cost function is augmented with geometric information derived from the 3D Harris operator applied to the high-resolution image. The robustness and accuracy of the proposed method were demonstrated using experiments on synthetic and clinical data including the brain and the tongue. The proposed method provided accurate registration and yielded better performance over standard registration methods. C1 [Woo, Jonghye] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Woo, Jonghye] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Stone, Maureen] Univ Maryland Baltimore Cty, Dept Neural & Pain Sci, Baltimore, MD 21250 USA. [Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RP Woo, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM jwoo@mgh.harvard.edu; stone@umaryland.edu; prince@jhu.edu FU National Institutes of Health [R01CA133015, R00DC012575] FX This work was supported by the National Institutes of Health under Grant R01CA133015 and Grant R00DC012575. The associate editor coordinating the review of this manuscript and approving it for publication was Dr. Quanzheng Li. NR 44 TC 7 Z9 7 U1 2 U2 26 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1057-7149 EI 1941-0042 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD FEB PY 2015 VL 24 IS 2 BP 757 EP + DI 10.1109/TIP.2014.2387019 PG 13 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA AZ7CH UT WOS:000348375400003 PM 25561595 ER PT J AU Li, Y Lu, Z Zhang, X Yu, H Kirkwood, KL Lopes-Virella, MF Huang, Y AF Li, Y. Lu, Z. Zhang, X. Yu, H. Kirkwood, K. L. Lopes-Virella, M. F. Huang, Y. TI Metabolic Syndrome Exacerbates Inflammation and Bone Loss in Periodontitis SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE lipopolysaccharide; palmitic acid; high-fat diet; osteoclast; cytokines; gene expression ID FREE FATTY-ACIDS; INSULIN-RESISTANCE; AGGRESSIVE PERIODONTITIS; DISEASE; ASSOCIATION; OBESITY; MACROPHAGES; EXPRESSION; MICROBIOTA; PALMITATE AB Clinical studies have shown that metabolic syndrome (MetS) is associated with increased risk of developing periodontitis. However, the underlying mechanisms remain largely unknown. Since it is known that lipopolysaccharide (LPS)-activated toll-like receptor 4 signaling pathways play a crucial role in periodontitis, we hypothesized that MetS enhances LPS-induced periodontal inflammation and alveolar bone loss. In this study, we induced MetS in C57BL/6 mice by feeding them high-fat diet (HFD), and we induced periodontitis by periodontal injection of Aggregatibacter actinomycetemcomitans LPS. We found that mice fed a HFD had significantly increased body weight, plasma lipids, insulin, and insulin resistance when compared with mice fed regular chow, indicating that the mice developed MetS. We also found that a HFD markedly increased LPS-induced alveolar bone loss, osteoclastogenesis, and inflammatory infiltration. Analysis of gene expression in periodontal tissue revealed that HFD and LPS injection cooperatively stimulated expression of cytokines that are known to be involved in periodontal tissue inflammation and osteoclastogenesissuch as interleukin 6, monocyte-chemotactic protein 1, receptor activator of nuclear factor kappa-B ligand, and macrophage colony-stimulating factor. To further understand the potential mechanisms involved in MetS-boosted tissue inflammation, our in vitro studies showed that palmitic acidthe most abundant saturated fatty acid (SFA) and the major SFA in the HFD used in our animal studypotently enhanced LPS-induced proinflammatory gene expression in macrophages. In sum, this study demonstrated that MetS was associated with increased periodontal inflammation and alveolar bone loss in an LPS-induced periodontitis animal model. This study also suggests that SFA palmitic acid may play an important role in MetS-associated periodontitis by enhancing LPS-induced expression of inflammatory cytokines in macrophages. C1 [Li, Y.; Lu, Z.; Zhang, X.; Lopes-Virella, M. F.; Huang, Y.] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Coll Med, Charleston, SC 29403 USA. [Yu, H.; Kirkwood, K. L.; Huang, Y.] Med Univ S Carolina, Dept Oral Hlth Sci, Coll Dent Med, Charleston, SC 29403 USA. [Lopes-Virella, M. F.; Huang, Y.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Dept Med, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU National Institutes of Health [DE016353]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development [5I01BX000854]; National Institute of General Medical Sciences [P30GM103331] FX This work was supported by grant DE016353 from the National Institutes of Health and grant 5I01BX000854 from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development (to Y.H.). This study utilized the facilities and resources of the Medical University of South Carolina Center for Oral Health Research, which is partially supported by grant P30GM103331 from the National Institute of General Medical Sciences. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 35 TC 6 Z9 7 U1 2 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2015 VL 94 IS 2 BP 362 EP 370 DI 10.1177/0022034514561658 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CA1BO UT WOS:000348647900016 PM 25503900 ER PT J AU Xiong, GX Redding, K Chen, B Cohen, AS Cohen, NA AF Xiong, Guoxiang Redding, Kevin Chen, Bei Cohen, Akiva S. Cohen, Noam A. TI Non-specific Immunostaining by a Rabbit Antibody against Gustducin alpha Subunit in Mouse Brain SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE taste bud; immunohistochemistry; peptide neutralization; axonal terminal; polyclonal antibody ID BITTER TASTE RECEPTORS; SOLITARY CHEMOSENSORY CELLS; GASTROINTESTINAL-TRACT; BURKHOLDERIA-CEPACIA; SWEET TASTE; RAT-BRAIN; IMMUNOHISTOCHEMISTRY; EXPRESSION; BUDS; SPECIFICITY AB Gustducin is a guanosine nucleotide-binding protein functionally coupled with taste receptors and thus originally identified in taste cells of the tongue. Recently, bitter taste receptors and gustducin have been detected in the airways, digestive tracts and brain. The existing studies showing taste receptors and gustducin in the brain were carried out exclusively on frozen sections. In order to avoid the technical shortcomings associated with frozen sectioning, we performed immunofluorescence staining using vibratome-cut sections from mouse brains. Using a rabbit gustducin antibody, we could not detect neurons or astrocytes as reported previously. Rather, we found dense fibers in the nucleus accumbens and periventricular areas. We assumed these staining patterns to be specific after confirmation with conventional negative control staining. For the verification of this finding, we stained gustducin knockout mouse brain and tongue sections with the same rabbit gustducin antibody. Whereas negative staining was confirmed in the tongue, intensive fibers were constantly stained in the brain. Moreover, immunostaining with a goat gustducin antibody could not demonstrate the fibers in the brain tissue. The present study implies a cross immunoreaction that occurs with the rabbit gustducin antibody in mouse brain samples, suggesting that the conventional negative controls may not be sufficient when an immunostaining pattern is to be verified. C1 [Xiong, Guoxiang; Cohen, Akiva S.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Redding, Kevin] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Chen, Bei; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Cohen, Akiva S.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Xiong, GX (reprint author), Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. EM xiong@email.chop.edu FU Flight Attendants Medical Research Institute FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a grant from The Flight Attendants Medical Research Institute and a philanthropic contribution from the RLG Foundation, Inc. (to NAC). NR 39 TC 2 Z9 2 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD FEB PY 2015 VL 63 IS 2 BP 79 EP 87 DI 10.1369/0022155414562838 PG 9 WC Cell Biology SC Cell Biology GA AZ9JP UT WOS:000348529900001 PM 25411190 ER PT J AU Hagiwara, Y Villarreal, D Sanchez-Reilly, S AF Hagiwara, Yuya Villarreal, Deborah Sanchez-Reilly, Sandra TI Present Planning versus Future Planning: We Need a Shift Toward Goals of Care Education for Physicians SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Letter C1 [Hagiwara, Yuya; Villarreal, Deborah; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA. [Villarreal, Deborah; Sanchez-Reilly, Sandra] South Texas Vet Hlth Care Syst, Geriatr Res Educ Clin Ctr, San Antonio, TX USA. RP Hagiwara, Y (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, 7703 Floyd Curl Dr,MSC 7875, San Antonio, TX 78229 USA. EM hagiwara@uthscsa.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD FEB 1 PY 2015 VL 18 IS 2 BP 99 EP 99 DI 10.1089/jpm.2014.0394 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ9IE UT WOS:000348526300004 PM 25546816 ER PT J AU Friedrichsdorf, SJ Postier, A Dreyfus, J Osenga, K Sencer, S Wolfe, J AF Friedrichsdorf, Stefan J. Postier, Andrea Dreyfus, Jill Osenga, Kaci Sencer, Susan Wolfe, Joanne TI Improved Quality of Life at End of Life Related to Home-Based Palliative Care in Children with Cancer SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID TERMINAL CARE; DEATH; HOSPICE; PARENTS; SYMPTOMS; SUPPORT; IMPACT AB Background: Nearly 2000 children die due to a malignancy in the United States annually. Emerging data suggest that home is the desired location of care for children with cancer at end of life. However, one obstacle to enrollment in a pediatric palliative care (PPC) home care program may be fear that distressing symptoms at end of life cannot be adequately managed outside the hospital. Objective: To compare the symptom distress and quality-of-life experience for children who received concurrent end-of-life care from a PPC home care program (PPC/Oncology) with that of those who died without exposure to the PPC program (Oncology). Methods: We conducted a retrospective survey study of a cohort of bereaved parents of children who died of cancer between 2002 and 2008 at a U.S. tertiary pediatric institution. Results: Sixty bereaved parents were surveyed (50% PPC/Oncology). Prevalence of constipation and high distress from fatigue were more common in the PPC/Oncology group; other distressing symptoms were similar between groups, showing room for improvement. Children who received PPC/Oncology were significantly more likely to have fun (70% versus 45%), to experience events that added meaning to life (89% versus 63%), and to die at home (93% versus 20%). Conclusions: This is the first North American study to assess outcomes among children with cancer who received concurrent oncology and palliative home care compared with those who received oncology care alone. Symptom distress experiences were similar in groups. However, children enrolled in a PPC home care program appear to have improved quality of life and are more likely to die at home. C1 [Friedrichsdorf, Stefan J.; Postier, Andrea; Osenga, Kaci] Childrens Hosp & Clin Minnesota, Dept Pain Med Palliat Care & Integrat Med, Minneapolis, MN 55404 USA. [Sencer, Susan] Childrens Hosp & Clin Minnesota, Dept Hematol Oncol, Minneapolis, MN 55404 USA. [Dreyfus, Jill] Childrens Hosp & Clin Minnesota, Res Program, Minneapolis, MN 55404 USA. [Dreyfus, Jill] Childrens Hosp & Clin Minnesota, Sponsored Program, Minneapolis, MN 55404 USA. [Friedrichsdorf, Stefan J.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. [Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Friedrichsdorf, SJ (reprint author), Childrens Hosp & Clin Minnesota, Dept Pain Med Palliat Care & Integrat Med, 2525 Chicago Ave S, Minneapolis, MN 55404 USA. EM stefan.friedrichsdorf@childrensMN.org FU CHC's Internal Research Grant Program (IRGP) FX This study was funded by CHC's Internal Research Grant Program (IRGP). The CHC IRGP was not involved in the conduction of the study or the development of this submission. We are grateful to Peter Lund, MDiv, for his research assistance and dedication to this project, and we are appreciative of the parents and families who took the time and energy to open up and share their very personal perspectives with us. NR 36 TC 8 Z9 8 U1 0 U2 11 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 FEB 1 PY 2015 VL 18 IS 2 BP 143 EP 150 DI 10.1089/jpm.2014.0285 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ9IE UT WOS:000348526300011 PM 25401507 ER PT J AU Shin, JA Back, AL AF Shin, Jennifer A. Back, Anthony L. TI A Snapshot of the Person Within: Using Smartphone Photos To Understand Values SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 [Shin, Jennifer A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Back, Anthony L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. RP Shin, JA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM jashin@partners.org FU NCI NIH HHS [R25CA092203, R25 CA092203] NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD FEB 1 PY 2015 VL 18 IS 2 BP 191 EP 192 DI 10.1089/jpm.2014.0201 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ9IE UT WOS:000348526300020 PM 25621599 ER PT J AU Goldstein, SA Evangelista, A Abbara, S Arai, A Asch, FM Badano, LP Bolen, MA Connolly, HM Cuellar-Calabria, H Czerny, M Devereux, RB Erbel, RA Fattori, R Isselbacher, EM Lindsay, JM McCulloch, M Michelena, HI Nienaber, CA Oh, JK Pepi, M Taylor, AJ Weinsaft, JW Zamorano, JL Dietz, H Eagle, K Elefteriades, J Jondeau, G Rousseau, H Schepens, M AF Goldstein, Steven A. Evangelista, Arturo Abbara, Suhny Arai, Andrew Asch, Federico M. Badano, Luigi P. Bolen, Michael A. Connolly, Heidi M. Cuellar-Calabria, Hug Czerny, Martin Devereux, Richard B. Erbel, Raimund A. Fattori, Rossella Isselbacher, Eric M. Lindsay, Joseph M. McCulloch, Marti Michelena, Hector I. Nienaber, Christoph A. Oh, Jae K. Pepi, Mauro Taylor, Allen J. Weinsaft, Jonathan W. Zamorano, Jose Luis Dietz, Harry Eagle, Kim Elefteriades, John Jondeau, Guillaume Rousseau, Herve Schepens, Marc TI Multimodality Imaging of Diseases of the Thoracic Aorta in Adults: From the American Society of Echocardiography and the European Association of Cardiovascular Imaging Endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID PENETRATING ATHEROSCLEROTIC ULCERS; INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHY; STENT-GRAFT IMPLANTATION; CORONARY-ARTERY-DISEASE; MULTIDETECTOR ROW CT; GIANT-CELL ARTERITIS; ENDOVASCULAR ANEURYSM REPAIR; 3-DIMENSIONAL MR-ANGIOGRAPHY; CONTRAST-INDUCED NEPHROPATHY; EXPERT CONSENSUS DOCUMENT C1 [Goldstein, Steven A.; Asch, Federico M.; Lindsay, Joseph M.; Taylor, Allen J.] Washington Hosp Ctr, Medstar Heart Inst, Washington, DC 20010 USA. [Evangelista, Arturo; Cuellar-Calabria, Hug] Vall dHebron Univ Hosp, Barcelona, Spain. [Abbara, Suhny] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Arai, Andrew] Natl Inst Hlth, Bethesda, MD USA. [Badano, Luigi P.] Univ Padua, Padua, Italy. [Bolen, Michael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Connolly, Heidi M.; Michelena, Hector I.; Oh, Jae K.] Mayo Clin, Rochester, MN USA. [Czerny, Martin] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Devereux, Richard B.; Weinsaft, Jonathan W.] Weill Cornell Med Coll, New York, NY USA. [Erbel, Raimund A.] Univ Duisburg Essen, West German Heart Ctr, Essen, Germany. [Fattori, Rossella] San Salvatore Hosp, Pesaro, Italy. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nienaber, Christoph A.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Nienaber, Christoph A.] Univ Rostock, D-18055 Rostock, Germany. [Pepi, Mauro] IRCCS, Ctr Cardiol Monzino, Milan, Italy. [Zamorano, Jose Luis] Univ Hosp Ramon y Cajal, Madrid, Spain. [Dietz, Harry] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Eagle, Kim] Univ Michigan, Ann Arbor, MI 48109 USA. [Elefteriades, John] Yale Univ, Sch Med, New Haven, CT USA. [Jondeau, Guillaume] Hop Bichat Claude Bernard, F-75877 Paris, France. [Rousseau, Herve] Hop Rangueil, Toulouse, France. [Schepens, Marc] AZ St Jan Brugge, Brugge, Belgium. RP Goldstein, SA (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org FU Siemens; GORE; Medtronic; Toshiba; Lantheus Medical Imaging FX The following authors reported relationships with one or more commercial interests: Suhny Abbara, MD, serves as a consultant for Perceptive Informatics. Andrew Arai, MD, receives research support from Siemens. Luigi P. Badano, MD, PhD, FESC, has received software and equipment from GE Healthcare, Siemens, and TomTec for research and testing purposes and is on the speakers' bureau of GE Healthcare. Kim Eagle, MD, received a research grant from GORE. John Elefteriades, MD, has a book published by CardioText and is a principal investigator on a grant and clinical trial from Medtronic. Jae K. Oh, MD, received a research grant from Toshiba and core laboratory support from Medtronic. Herve Rousseau, MD, serves as a consultant for GORE, Medtronic, and Bolton. Jonathan W. Weinsaft, MD, received a research grant from Lantheus Medical Imaging. NR 440 TC 45 Z9 46 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD FEB PY 2015 VL 28 IS 2 BP 119 EP 182 DI 10.1016/j.echo.2014.11.015 PG 64 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ8HU UT WOS:000348457200002 PM 25623219 ER PT J AU Matsushita, K Sang, YY Ballew, SH Shlipak, M Katz, R Rosas, SE Peralta, CA Woodward, M Kramer, HJ Jacobs, DR Sarnak, MJ Coresh, J AF Matsushita, Kunihiro Sang, Yingying Ballew, Shoshana H. Shlipak, Michael Katz, Ronit Rosas, Sylvia E. Peralta, Carmen A. Woodward, Mark Kramer, Holly J. Jacobs, David R. Sarnak, Mark J. Coresh, Josef TI Subclinical Atherosclerosis Measures for Cardiovascular Prediction in CKD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; CORONARY-ARTERY CALCIUM; AMERICAN-HEART-ASSOCIATION; INTIMA-MEDIA THICKNESS; ANKLE-BRACHIAL INDEX; RISK-FACTORS; PRACTICE GUIDELINES; CYSTATIN C; TASK-FORCE AB Whether inclusion of the coronary artery calcium score improves cardiovascular risk prediction in individuals with CKD, a population with unique calcium-phosphate homeostasis, is unknown. Among 6553 participants ages 45-84 years without prior cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, coronary artery calcium score was assessed for cardiovascular risk prediction beyond the Framingham predictors in those with (n=1284) and without CKD and contrasted with carotid intimamedia thickness and ankle-brachial index (two other measures of subclinical atherosclerosis). During a median follow-up of 8.4 years, 650 cardiovascular events (coronary heart disease, stroke, heart failure, and peripheral artery disease) occurred (236 events in subjects with CKD). In Cox proportional hazards models adjusted for Framingham predictors, each subclinical measure was independently associated with cardiovascular outcomes, with larger adjusted hazard ratios (HRs; per 1 SD) for coronary artery calcium score than carotid intima-media thickness or ankle-brachial index in subjects without and with CKD (HR, 1.69; 95% confidence interval [95% CI], 1.45 to 1.97 versus HR, 1.12; 95% Cl, 1.00 to 1.25 and HR, 1.20; 95% Cl, 1.08 to 1.32, respectively). Compared with inclusion of carotid intima-media thickness or ankle-brachial index, inclusion of the coronary artery calcium score led to greater increases in C statistic for predicting cardiovascular disease and net reclassification improvement. Coronary artery calcium score performed best for the prediction of coronary heart disease and heart failure, regardless of CKD status. In conclusion, each measure improved cardiovascular risk prediction in subjects with CKD, with the greatest improvement observed with coronary artery calcium score. C1 [Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana H.; Woodward, Mark; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Shlipak, Michael] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. [Shlipak, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Shlipak, Michael] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Peralta, Carmen A.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Katz, Ronit] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Rosas, Sylvia E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Peralta, Carmen A.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Kramer, Holly J.] Loyola Univ, Med Ctr, Div Nephrol, Maywood, IL 60153 USA. [Jacobs, David R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. RP Matsushita, K (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. EM kmatsush@jhsph.edu RI Woodward, Mark/D-8492-2015 FU National Heart, Lung, and Blood Institute [N01-HC-95159-N01-HC-95169]; National Center for Research Resource [UL1-RR-024156, UL1-RR-025005] FX This research was supported by National Heart, Lung, and Blood Institute Contracts N01-HC-95159-N01-HC-95169 and National Center for Research Resource Grants UL1-RR-024156 and UL1-RR-025005. NR 40 TC 23 Z9 25 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2015 VL 26 IS 2 BP 439 EP 447 DI 10.1681/ASN.2014020173 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CA0RG UT WOS:000348623700021 PM 25145930 ER PT J AU Drain, PK AF Drain, Paul K. TI Ebola: lessons learned from HIV and tuberculosis epidemics SO LANCET INFECTIOUS DISEASES LA English DT Letter ID TESTS C1 [Drain, Paul K.] Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Drain, Paul K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Drain, PK (reprint author), Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. EM pdrain@partners.org FU FIC NIH HHS [R24 TW007988]; NIAID NIH HHS [K23 AI108293, T32 AI007433, P30 AI060354] NR 4 TC 4 Z9 4 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD FEB PY 2015 VL 15 IS 2 BP 146 EP 147 PG 2 WC Infectious Diseases SC Infectious Diseases GA AZ7PJ UT WOS:000348410200012 PM 25749061 ER PT J AU Mitra, M Iezzoni, LI Zhang, JY Long-Bellil, LM Smeltzer, SC Barton, BA AF Mitra, Monika Iezzoni, Lisa I. Zhang, Jianying Long-Bellil, Linda M. Smeltzer, Suzanne C. Barton, Bruce A. TI Prevalence and Risk Factors for Postpartum Depression Symptoms Among Women with Disabilities SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Disability; Postpartum depression; Women with disabilities; Pregnancy ID PHYSICAL-DISABILITIES; PREGNANT-WOMEN; MATERNAL DEPRESSION; BIRTH CERTIFICATE; SUBSTANCE USE; IMPACT; EXPERIENCES; MOTHERS; HEALTH; METAANALYSIS AB The adverse consequences of postpartum depression on the health of the mother and her child are well documented. However, there is little information on postpartum depression among mothers with disabilities. This study examines the patterns of depression and depressive symptoms before, during and after pregnancy and the association between depression before and during pregnancy and postpartum depression symptomatology (PPD) among women with and without disabilities. Data from the 2009-2011 Rhode Island Pregnancy Risk Assessment Monitoring System (PRAMS) were analyzed in 2013. Almost 30 % (28.9 %; 95 % CI 22.8-35.8) of mothers with disabilities reported often or always feeling down, depressed or sad after childbirth compared to 10 % of those without disabilities (95 % CI 8.9-11.3). Compared to other women in the study, women with disabilities had a greater likelihood for PPD symptoms (RR 1.6, 95 % CI 1.1-2.2) after accounting for sociodemographics, maternal characteristics related to PPD, and depression before and during pregnancy. Adjusting for other covariates, self-reported prenatal diagnosis of depression was not associated with symptoms of PPD and depression during pregnancy was marginally associated with PPD symptomatology for women with disabilities. Women with disabilities are at a greater risk of experiencing symptoms of postpartum depression than other women. Screening for PPD among new mothers with disabilities and timely referral of those with PPD diagnosis are vital to the health of mothers with disabilities and their children. C1 [Mitra, Monika; Zhang, Jianying; Long-Bellil, Linda M.] Univ Massachusetts, Ctr Hlth Policy & Res, Sch Med, Shrewsbury, MA 01545 USA. [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Smeltzer, Suzanne C.] Villanova Univ, Ctr Nursing Res, Villanova, PA 19085 USA. [Barton, Bruce A.] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. RP Mitra, M (reprint author), Univ Massachusetts, Ctr Hlth Policy & Res, Sch Med, 333 South St, Shrewsbury, MA 01545 USA. EM monika.mitra@umassmed.edu; liezzoni@partners.org; Jianying.zhang@umassmed.edu; linda.long@umassmed.edu; Suzanne.smeltzer@villanova.edu; Bruce.barton@umassmed.edu OI Barton, Bruce/0000-0001-7878-8895 FU NICHD NIH HHS [1R01HD074581, R01 HD074581] NR 51 TC 5 Z9 5 U1 3 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 EI 1573-6628 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD FEB PY 2015 VL 19 IS 2 SI SI BP 362 EP 372 DI 10.1007/s10995-014-1518-8 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AZ6TP UT WOS:000348353600020 PM 24889114 ER PT J AU Lee, JJ Granter, SR Laga, AC Saavedra, AP Zhan, Q Guo, WM Xu, SY Murphy, GF Lian, CG AF Lee, Jonathan J. Granter, Scott R. Laga, Alvaro C. Saavedra, Arturo P. Zhan, Qian Guo, Weimin Xu, Shuyun Murphy, George F. Lian, Christine G. TI 5-Hydroxymethylcytosine expression in metastatic melanoma versus nodal nevus in sentinel lymph node biopsies SO MODERN PATHOLOGY LA English DT Article ID MELANOCYTIC NEVI; CUTANEOUS NEVI; USEFUL MARKER; SOX2; DIFFERENTIATE; NESTIN; CELLS; P16 AB Sentinel lymph node biopsies are conducted to stage patients with newly diagnosed melanomas that have histopathological attributes conferring defined levels of metastatic potential. Because benign nevic cells may also form 'deposits' in lymph nodes (nodal nevus), the pathological evaluation for metastatic melanoma within sentinel lymph nodes can be challenging. Twenty-eight sentinel lymph node biopsy cases containing either metastatic melanoma (N= 18) or nodal nevi (N= 10) were retrieved from the archives of the Brigham and Women's Hospital, Department of Pathology (2011-2014). In addition, two sentinel lymph node cases that were favored to represent metastatic disease but whose histopathological features were viewed as equivocal, with melanoma favored, were also included. Dual labeling for the melanocyte lineage marker, MART-1, and the epigenetic marker, 5-hydroxymethylcytosine, a functionally significant indicator that has been shown to distinguish benign nevi from melanoma, was performed on all cases using immunohistochemistry and/or direct immunofluorescence. All (18 of 18) metastatic melanoma cases showed complete loss of 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells, and all (10 of 10) nodal nevus cases demonstrated 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells. In addition, 5-hydroxymethylcytosine staining confirmed the favored diagnoses of metastatic melanoma in the two 'equivocal' cases. Thus, 5-hydroxymethylcytosine may be a useful adjunctive marker to distinguish between benign nodal nevi and metastatic melanoma during the evaluation of sentinel lymph node biopsies for metastatic melanoma. C1 [Lee, Jonathan J.; Granter, Scott R.; Laga, Alvaro C.; Saavedra, Arturo P.; Zhan, Qian; Guo, Weimin; Xu, Shuyun; Murphy, George F.; Lian, Christine G.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Program Dermatopathol,Med Sch, Boston, MA 02115 USA. [Saavedra, Arturo P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Murphy, GF (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Program Dermatopathol,Med Sch, 221 Longwood Ave,EBRC Suite 401, Boston, MA 02115 USA. EM gmurphy@rics.bwh.harvard.edu; cglian@partners.org RI Guo, Weimin/B-3155-2009; OI Guo, Weimin/0000-0003-4318-7154; Lian, Christine/0000-0003-4626-1612 FU NIH [5P40CA093683-09]; Women's Hospital; Bristol-Meyers-Squibb FX These results were shared, in part, at the Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School Department of Pathology Annual Research Celebration (2014) in Boston, MA, USA. This study is supported by NIH grant 5P40CA093683-09 to the SPORE Core at Brigham and Women's Hospital. GFM receives funding from Bristol-Meyers-Squibb for work on melanoma biomarkers (not a funding source for this study). NR 23 TC 9 Z9 9 U1 0 U2 3 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 FEB PY 2015 VL 28 IS 2 BP 218 EP 229 DI 10.1038/modpathol.2014.99 PG 12 WC Pathology SC Pathology GA CA5NY UT WOS:000348956300006 PM 25081754 ER PT J AU Kamat, SS Camara, K Parsons, WH Chen, DH Dix, MM Bird, TD Howell, AR Cravatt, BF AF Kamat, Siddhesh S. Camara, Kaddy Parsons, William H. Chen, Dong-Hui Dix, Melissa M. Bird, Thomas D. Howell, Amy R. Cravatt, Benjamin F. TI Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay SO NATURE CHEMICAL BIOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; SERINE HYDROLASES; ENDOCANNABINOID 2-ARACHIDONOYLGLYCEROL; PHOSPHOLIPASE A(1); HISTAMINE-RELEASE; GRAVES-DISEASE; X-CHROMOSOME; MAST-CELLS; BRAIN; PHOSPHATIDYLSERINE AB Lysophosphatidylserines (lyso-PSs) are a class of signaling lipids that regulate immunological and neurological processes. The metabolism of lyso-PSs remains poorly understood in vivo. Recently, we determined that ABHD12 is a major brain lyso-PS lipase, implicating lyso-PSs in the neurological disease polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and cataract (PHARC), which is caused by null mutations in the ABHD12 gene. Here, we couple activity-based profiling with pharmacological and genetic methods to annotate the poorly characterized enzyme ABHD16A as a phosphatidylserine (PS) lipase that generates lyso-PS in mammalian systems. We describe a small-molecule inhibitor of ABHD16A that depletes lyso-PSs from cells, including lymphoblasts derived from subjects with PHARC. In mouse macrophages, disruption of ABHD12 and ABHD16A respectively increases and decreases both lyso-PSs and lipopolysaccharide-induced cytokine production. Finally, Abhd16a(-/-) mice have decreased brain lyso-PSs, which runs counter to the elevation in lyso-PS in Abhd12(-/-) mice. Our findings illuminate an ABHD16A-ABHD12 axis that dynamically regulates lyso-PS metabolism in vivo, designating these enzymes as potential targets for treating neuroimmunological disorders. C1 [Kamat, Siddhesh S.; Parsons, William H.; Dix, Melissa M.; Cravatt, Benjamin F.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA. [Kamat, Siddhesh S.; Parsons, William H.; Dix, Melissa M.; Cravatt, Benjamin F.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Camara, Kaddy; Howell, Amy R.] Univ Connecticut, Dept Chem, Storrs, CT USA. [Chen, Dong-Hui; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Bird, Thomas D.] Univ Washington, Dept Med, Seattle, WA USA. [Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Cravatt, BF (reprint author), Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA. EM cravatt@scripps.edu OI Parsons, William/0000-0001-6065-2340 FU US National Institutes of Health [DA033760]; American Chemical Society; Hewitt Foundation for Medical Research fellowship; Department of Veterans Affairs Research Funds; US National Science Foundation [CHE-0809753, CHE-1048717] FX We are grateful to K. Masuda, A. Viader and K.-L. Hsu for their helpful discussions, guidance and technical expertise in harvesting tissues; G. Simon and J. Blankman for helpful discussions; M. Niphakis for advice on the SAR studies on the beta-lactone scaffolds; O. Ulanovskaya for advice on generating the shRNA knockdown cell lines; B. Correia for the guidance on using CIMAGE; C. Joslyn and T. Takei for technical assistance; and M. Lau for contributions to initial synthetic studies. This work was supported by the US National Institutes of Health (DA033760) and the ninth Irving S. Sigal postdoctoral fellowship from the American Chemical Society (to S.S.K.), a Hewitt Foundation for Medical Research fellowship (to W.H.P.), the Department of Veterans Affairs Research Funds (to T.D.B.) and the US National Science Foundation (CHE-0809753 and CHE-1048717 to A.R.H.). NR 49 TC 21 Z9 21 U1 1 U2 17 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 FEB PY 2015 VL 11 IS 2 BP 164 EP U116 DI 10.1038/NCHEMBIO.1721 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ6WN UT WOS:000348358800015 PM 25580854 ER PT J AU O'Dushlaine, C Rossin, L Lee, PH Duncan, L Parikshak, NN Newhouse, S Ripke, S Neale, BM Purcell, SM Posthuma, D Nurnberger, JI Lee, SH Faraone, SV Perlis, RH Mowry, BJ Thapar, A Goddard, ME Witte, JS Absher, D Agartz, I Akil, H Amin, F Andreassen, OA Anjorin, A Anney, R Anttila, V Arking, DE Asherson, P Azevedo, MH Backlund, L Badner, JA Bailey, AJ Banaschewski, T Barchas, JD Barnes, MR Barrett, TB Bass, N Battaglia, A Bauer, M Bayes, M Bellivier, F Bergen, SE Berrettini, W Betancur, C Bettecken, T Biederman, J Binder, EB Black, DW Blackwood, DHR Bloss, CS Boehnke, M Boomsma, DI Breuer, R Bruggeman, R Cormican, P Buccola, NG Buitelaar, JK Bunney, WE Buxbaum, JD Byerley, WF Byrne, EM Caesar, S Cahn, W Cantor, RM Casas, M Chakravarti, A Chambert, K Choudhury, K Cichon, S Mattheisen, M Cloninger, CR Collier, DA Cook, EH Coon, H Cormand, B Corvin, A Coryell, WH Craig, DW Craig, IW Crosbie, J Cuccaro, ML Curtis, D Czamara, D Datta, S Dawson, G Day, R De Geus, EJ Degenhardt, F Djurovic, S Donohoe, GJ Doyle, AE Duan, J Dudbridge, F Duketis, E Ebstein, RP Edenberg, HJ Elia, J Ennis, S Etain, B Fanous, A Farmer, AE Ferrier, IN Flicldnger, M Fombonne, E Foroud, T Frank, J Franke, B Fraser, C Freedman, R Freimer, NB Freitag, CM Friedl, M Frisen, L Gailagher, L Gejman, PV Georgieva, L Gershon, ES Giegling, I Gill, M Gordon, SD Gordon-Smith, K Green, EK Greenwood, TA Grice, DE Gross, M Grozeva, D Guan, W Gurling, H De Haan, L Haines, JL Hakonarson, H Hallmayer, J Hamilton, SP Hamshere, ML Hansen, TF Hartmann, AM Hautzinger, M Heath, AC Henders, AK Herms, S Hickie, IB Hipolito, M Hoefels, S Holsboer, F Hoogendijk, WJ Hottenga, JJ Hultman, CM Hus, V Ingason, A Ising, M Jamain, S Jones, EG Jones, I Jones, L Tzeng, JY Kahler, AK Kahn, RS Kandaswamy, R Keller, MC Kennedy, JL Kenny, E Kent, L Kim, YJ Kirov, GK Klauck, SM Klei, L Knowles, JA Kohli, MA Koller, DL Konte, B Korszun, A Krabbendam, L Krasucki, R Kuntsi, J Kwan, P Landen, M Langstrom, N Lathrop, M Lawrence, J Lawson, WB Leboyer, M Ledbetter, DH Lencz, T Lesch, KP Levinson, DF Lewis, CM Li, J Lichtenstein, P Lieberman, JA Lin, DY Linszen, DH Liu, CY Lohoff, FW Loo, SK Lord, C Lowe, JK Lucae, S MacIntyre, DJ Madden, PAF Maestrini, E Magnusson, PKE Mahon, PB Maier, W Malhotra, AK Mane, SM Martin, CL Martin, NG Matthews, K Mattingsdal, M McCarroll, SA McGhee, KA McGough, JJ McGrath, PJ McGuffin, P McInnis, MG McIntosh, A McKinney, R McLean, AW McMahon, FJ McMahon, WM McQuillin, A Medeiros, H Medland, SE Meier, S Melle, I Meng, F Meyer, J Middeldorp, CM Middleton, L Milanova, V Miranda, A Monaco, AP Montgomery, GW Moran, JL Moreno-De-Luca, D Morken, G Morris, DW Morrow, EM Moskvina, V Muglia, P Muhleisen, TW Muir, WJ Muller-Myhsok, B Murtha, M Myers, RM Myin-Germeys, I Neale, MC Nelson, SF Nievergelt, CM Nikolov, I Nimgaonkar, V Nolen, WA Nothen, MM Nwulia, EA Nyholt, DR Oades, RD Olincy, A Oliveira, G Olsen, L Ophoff, RA Osby, U Owen, MJ Palotie, A Parr, JR Paterson, AD Pato, CN Pato, MT Penninx, BW Pergadia, ML Pericak-Vance, MA Pickard, BS Pimm, J Piven, J Potash, JB Poustka, F Propping, P Puri, V Quested, DJ Quinn, EM Ramos-Quiroga, JA Rasmussen, HB Raychaudhuri, S Rehnstrom, K Reif, A Ribases, M Rice, JP Rietschel, M Roeder, K Roeyers, H Rothenberger, A Rouleau, G Ruderfer, D Rujescu, D Sanders, AR Sanders, SJ Santangelo, SL Sergeant, JA Schachar, R Schalling, M Schatzberg, AF Scheftner, WA Schellenberg, GD Scherer, SW Schork, NJ Schulze, TG Schumacher, J Schwarz, M Scolnick, E Scott, LJ Shi, JX Shilling, PD Shyn, SI Silverman, JM Slager, SL Smalley, SL Smit, JH Smith, EN Sonuga-Barke, EJS Cair, DS State, M Steffens, M Steinhausen, HC Strauss, JS Strohmaier, J Stroup, TS Sutdiffe, JS Szatmari, P Szelinger, S Thirumalai, S Thompson, RC Todorov, AA Tozzi, F Treutlein, J Uhr, M Van den Oord, EJCG Van Grootheest, G Van Os, J Vicente, AM Vieland, VJ Vincent, JB Visscher, PM Walsh, CA Wassink, TH Watson, SJ Weissman, MM Werge, T Wienker, TF Wijsman, EM Willemsen, G Williams, N Willsey, AJ Witt, SH Xu, W Young, AH Yu, TW Zammit, S Zandi, PP Zhang, P Zitman, FG Zollner, S Devlin, B Kelsoe, JR Sklar, P Daly, MJ O'Donovan, MC Craddock, N Kendler, KS Weiss, LA Wray, NR Zhao, ZM Geschwind, DH Sullivan, PF Smoller, JW Holmans, PA Breen, G AF O'Dushlaine, Colm Rossin, Lizzy Lee, Phil H. Duncan, Laramie Parikshak, Neelroop N. Newhouse, Stephen Ripke, Stephan Neale, Benjamin M. Purcell, Shaun M. Posthuma, Danielle Nurnberger, John I. Lee, S. Hong Faraone, Stephen V. Perlis, Roy H. Mowry, Bryan J. Thapar, Anita Goddard, Michael E. Witte, John S. Absher, Devin Agartz, Ingrid Akil, Huda Amin, Farooq Andreassen, Ole A. Anjorin, Adebayo Anney, Richard Anttila, Verneri Arking, Dan E. Asherson, Philip Azevedo, Maria H. Backlund, Lena Badner, Judith A. Bailey, Anthony J. Banaschewski, Tobias Barchas, Jack D. Barnes, Michael R. Barrett, Thomas B. Bass, Nicholas Battaglia, Agatino Bauer, Michael Bayes, Monica Bellivier, Frank Bergen, Sarah E. Berrettini, Wade Betancur, Catalina Bettecken, Thomas Biederman, Joseph Binder, Elisabeth B. Black, Donald W. Blackwood, Douglas H. R. Bloss, Cinnamon S. Boehnke, Michael Boomsma, Dorret I. Breuer, Rene Bruggeman, Richard Cormican, Paul Buccola, Nancy G. Buitelaar, Jan K. Bunney, William E. Buxbaum, Joseph D. Byerley, William F. Byrne, Enda M. Caesar, Sian Cahn, Wiepke Cantor, Rita M. Casas, Miguel Chakravarti, Aravinda Chambert, Kimberly Choudhury, Khalid Cichon, Sven Mattheisen, Manuel Cloninger, C. Robert Collier, David A. Cook, Edwin H. Coon, Hilary Cormand, Bru Corvin, Aiden Coryell, William H. Craig, David W. Craig, Ian W. Crosbie, Jennifer Cuccaro, Michael L. Curtis, David Czamara, Darina Datta, Susmita Dawson, Geraldine Day, Richard De Geus, Eco J. Degenhardt, Franziska Djurovic, Srdjan Donohoe, Gary J. Doyle, Alysa E. Duan, Jubao Dudbridge, Frank Duketis, Eftichia Ebstein, Richard P. Edenberg, Howard J. Elia, Josephine Ennis, Sean Etain, Bruno Fanous, Ayman Farmer, Anne E. Ferrier, I. Nicol Flicldnger, Matthew Fombonne, Eric Foroud, Tatiana Frank, Josef Franke, Barbara Fraser, Christine Freedman, Robert Freimer, Nelson B. Freitag, Christine M. Friedl, Marion Frisen, Louise Gailagher, Louise Gejman, Pablo V. Georgieva, Lyudmila Gershon, Elliot S. Giegling, Ina Gill, Michael Gordon, Scott D. Gordon-Smith, Katherine Green, Elaine K. Greenwood, Tiffany A. Grice, Dorothy E. Gross, Magdalena Grozeva, Detelina Guan, Weihua Gurling, Hugh De Haan, Lieuwe Haines, Jonathan L. Hakonarson, Hakon Hallmayer, Joachim Hamilton, Steven P. Hamshere, Marian L. Hansen, Thomas F. Hartmann, Annette M. Hautzinger, Martin Heath, Andrew C. Henders, Anjali K. Herms, Stefan Hickie, Ian B. Hipolito, Maria Hoefels, Susanne Holsboer, Florian Hoogendijk, Witte J. Hottenga, Jouke-Jan Hultman, Christina M. Hus, Vanessa Ingason, Andres Ising, Marcus Jamain, Stephane Jones, Edward G. Jones, Ian Jones, Lisa Tzeng, Jung-Ying Kaehler, Anna K. Kahn, Rene S. Kandaswamy, Radhika Keller, Matthew C. Kennedy, James L. Kenny, Elaine Kent, Lindsey Kim, Yunjung Kirov, George K. Klauck, Sabine M. Klei, Lambertus Knowles, James A. Kohli, Martin A. Koller, Daniel L. Konte, Bettina Korszun, Ania Krabbendam, Lydia Krasucki, Robert Kuntsi, Jonna Kwan, Phoenix Landen, Mikael Laengstroem, Niklas Lathrop, Mark Lawrence, Jacob Lawson, William B. Leboyer, Marion Ledbetter, David H. Lencz, Todd Lesch, Klaus-Peter Levinson, Douglas F. Lewis, Cathryn M. Li, Jun Lichtenstein, Paul Lieberman, Jeffrey A. Lin, Dan-Yu Linszen, Don H. Liu, Chunyu Lohoff, Falk W. Loo, Sandra K. Lord, Catherine Lowe, Jennifer K. Lucae, Susanne MacIntyre, Donald J. Madden, Pamela A. F. Maestrini, Elena Magnusson, Patrik K. E. Mahon, Pamela B. Maier, Wolfgang Malhotra, Anil K. Mane, Shrikant M. Martin, Christa L. Martin, Nicholas G. Matthews, Keith Mattingsdal, Morten McCarroll, Steven A. McGhee, Kevin A. McGough, James J. McGrath, Patrick J. McGuffin, Peter McInnis, Melvin G. McIntosh, Andrew McKinney, Rebecca McLean, Alan W. McMahon, Francis J. McMahon, William M. McQuillin, Andrew Medeiros, Helena Medland, Sarah E. Meier, Sandra Melle, Ingrid Meng, Fan Meyer, Jobst Middeldorp, Christel M. Middleton, Lefkos Milanova, Vihra Miranda, Ana Monaco, Anthony P. Montgomery, Grant W. Moran, Jennifer L. Moreno-De-Luca, Daniel Morken, Gunnar Morris, Derek W. Morrow, Eric M. Moskvina, Valentina Muglia, Pierandrea Muehleisen, Thomas W. Muir, Walter J. Mueller-Myhsok, Bertram Murtha, Michael Myers, Richard M. Myin-Germeys, Inez Neale, Michael C. Nelson, Stan F. Nievergelt, Caroline M. Nikolov, Ivan Nimgaonkar, Vishwajit Nolen, Willem A. Noethen, Markus M. Nwulia, Evaristus A. Nyholt, Dale R. Oades, Robert D. Olincy, Ann Oliveira, Guiomar Olsen, Line Ophoff, Roel A. Osby, Urban Owen, Michael J. Palotie, Aarno Parr, Jeremy R. Paterson, Andrew D. Pato, Carlos N. Pato, Michele T. Penninx, Brenda W. Pergadia, Michele L. Pericak-Vance, Margaret A. Pickard, Benjamin S. Pimm, Jonathan Piven, Joseph Potash, James B. Poustka, Fritz Propping, Peter Puri, Vinay Quested, Digby J. Quinn, Emma M. Ramos-Quiroga, Josep Antoni Rasmussen, Henrik B. Raychaudhuri, Soumya Rehnstroem, Karola Reif, Andreas Ribases, Marta Rice, John P. Rietschel, Marcella Roeder, Kathryn Roeyers, Herbert Rothenberger, Aribert Rouleau, Guy Ruderfer, Douglas Rujescu, Dan Sanders, Alan R. Sanders, Stephan J. Santangelo, Susan L. Sergeant, Joseph A. Schachar, Russell Schalling, Martin Schatzberg, Alan F. Scheftner, William A. Schellenberg, Gerard D. Scherer, Stephen W. Schork, Nicholas J. Schulze, Thomas G. Schumacher, Johannes Schwarz, Markus Scolnick, Edward Scott, Laura J. Shi, Jianxin Shilling, Paul D. Shyn, Stanley I. Silverman, Jeremy M. Slager, Susan L. Smalley, Susan L. Smit, Johannes H. Smith, Erin N. Sonuga-Barke, Edmund J. S. Cair, David St. State, Matthew Steffens, Michael Steinhausen, Hans-Christoph Strauss, John S. Strohmaier, Jana Stroup, T. Scott Sutdiffe, James S. Szatmari, Peter Szelinger, Szabocls Thirumalai, Srinivasa Thompson, Robert C. Todorov, Alexandre A. Tozzi, Federica Treutlein, Jens Uhr, Manfred Van den Oord, Edwin J. C. G. Van Grootheest, Gerard Van Os, Jim Vicente, Astrid M. Vieland, Veronica J. Vincent, John B. Visscher, Peter M. Walsh, Christopher A. Wassink, Thomas H. Watson, Stanley J. Weissman, Myrna M. Werge, Thomas Wienker, Thomas F. Wijsman, Ellen M. Willemsen, Gonneke Williams, Nigel Willsey, A. Jeremy Witt, Stephanie H. Xu, Wei Young, Allan H. Yu, Timothy W. Zammit, Stanley Zandi, Peter P. Zhang, Peng Zitman, Frans G. Zoellner, Sebastian Devlin, Bernie Kelsoe, John R. Sklar, Pamela Daly, Mark J. O'Donovan, Michael C. Craddock, Nicholas Kendler, Kenneth S. Weiss, Lauren A. Wray, Naomi R. Zhao, Zhaoming Geschwind, Daniel H. Sullivan, Patrick F. Smoller, Jordan W. Holmans, Peter A. Breen, Gerome CA IIBDGC Network & Pathway Anal Subgrp Psyc TI Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways SO NATURE NEUROSCIENCE LA English DT Article ID DE-NOVO MUTATIONS; SCHIZOPHRENIA; METHYLATION; DISORDERS; AUTISM; BRAIN; PROMOTERS; BURDEN; LOCI AB Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders. C1 [O'Dushlaine, Colm] Regeneron Pharmaceut Inc, Regeneron Genet Ctr, Tarrytown, NY 10591 USA. [O'Dushlaine, Colm; Rossin, Lizzy; Duncan, Laramie; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Perlis, Roy H.; Anttila, Verneri; Raychaudhuri, Soumya; Daly, Mark J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. 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[Schatzberg, Alan F.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Scheftner, William A.] Rush Univ Med Ctr, Chicago, IL USA. [Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Gen, Toronto, ON M5G 1X8, Canada. [Schork, Nicholas J.; Smith, Erin N.] Scripps Res Inst, La Jolla, CA 92037 USA. [Schulze, Thomas G.] Univ Gottingen, Dept Psychiat & Psychotherapy, D-37073 Gottingen, Germany. [Schwarz, Markus] Psychiat Ctr Nordbaden, Wiesloch, Germany. [Shi, Jianxin] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Shyn, Stanley I.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Slager, Susan L.] Mayo Clin, Rochester, MN USA. [Sonuga-Barke, Edmund J. S.] Univ Southampton, Acad Unit Psychol, Developmental Brain & Behav Lab, Southampton, Hants, England. [Cair, David St.] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland. [Steffens, Michael] Fed Inst Drugs & Med Devices BfArM, Res Dept, Bonn, Germany. [Steinhausen, Hans-Christoph] Aalborg Univ Hosp, Res Unit Child & Adolescent Psychiat, Aalborg, Denmark. Univ Basel, Clin Psychol & Epidemiol, Basel, Switzerland. [Steinhausen, Hans-Christoph] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland. [Strauss, John S.] Ctr Addict & Mental Hlth, Mol Neuropsychiat & Dev Lab, Toronto, ON, Canada. [Stroup, T. Scott; Vincent, John B.] Columbia Univ, Dept Psychiat, New York, NY USA. [Sutdiffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Nashville, TN 37235 USA. [Szatmari, Peter] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Hosp Sick Children, Neurosci & Mental Hlth Program, Toronto, ON M5G 1X8, Canada. [Szatmari, Peter] Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Thirumalai, Srinivasa] Oxford Hlth NHS Fdn Trust, Marlborough House Secure Unit, Milton Keynes, Bucks, England. [Van den Oord, Edwin J. C. G.] Virginia Commonwealth Univ, Ctr Biomarker Res & Personalized Med, Richmond, VA USA. Inst Nacl Saude Dr Ricardo Jorge, Lisbon, Portugal. [Vicente, Astrid M.] BioFIG, Ctr Biodivers, Funct & Integrat Gen, Lisbon, Portugal. Inst Gulbenkian Ciencias, Lisbon, Portugal. [Vicente, Astrid M.] Nationwide Childrens Hosp, Battelle Ctr Math Med, Columbus, OH USA. [Vieland, Veronica J.; Walsh, Christopher A.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Life Sci, Dept Neurol, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Ctr Life Sci, Dept Paediat, Boston, MA 02115 USA. [Weissman, Myrna M.] Columbia Univ, Coll Physicians & Surg, New York, NY USA. [Werge, Thomas] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark. [Wienker, Thomas F.] Univ Bonn, Inst Med Biometry, Bonn, Germany. [Wijsman, Ellen M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Wijsman, Ellen M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Young, Allan H.] Kings Coll London, Inst Psychiat, Ctr Affect Disorders, London, England. [Yu, Timothy W.] Harvard Univ, Sch Med, Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Zandi, Peter P.] Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD USA. [Zitman, Frans G.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, STEP, Dept Psychiat, San Diego, CA USA. Virginia Commonwealth Univ, Dept Human Mol Genet, Richmond, VA USA. [Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Kendler, Kenneth S.] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA. [Zhao, Zhaoming] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. RP Breen, G (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, MRC, London, England. EM holmanspa@cardiff.ac.uk; gerome.breen@kcl.ac.uk RI Holmans, Peter/F-4518-2015; Kuntsi, Jonna/G-9750-2011; Zhang, Peng/N-2920-2014; Mattheisen, Manuel/B-4949-2012; Breen, Gerome/A-5540-2010; Monaco, Anthony/A-4495-2010; Scherer, Stephen /B-3785-2013; Franke, Barbara/D-4836-2009; Hansen, Thomas/O-5965-2014; Paterson, Andrew/A-4088-2011; Melle, Ingrid /B-4858-2011; Schumacher, Johannes/F-4970-2015; Ruderfer, Douglas/M-5795-2016; Lee, Sang Hong/A-2569-2011; Lohoff, Falk/M-7951-2016; Lencz, Todd/J-3418-2014; BELLIVIER, FRANK/H-5197-2012; McQuillin, Andrew/C-1623-2008; Magnusson, Patrik/C-4458-2017; Lesch, Klaus-Peter/J-4906-2013; OI Holmans, Peter/0000-0003-0870-9412; Zhang, Peng/0000-0003-1182-1392; Mattheisen, Manuel/0000-0002-8442-493X; Breen, Gerome/0000-0003-2053-1792; Monaco, Anthony/0000-0001-7480-3197; Scherer, Stephen /0000-0002-8326-1999; Franke, Barbara/0000-0003-4375-6572; Hansen, Thomas/0000-0001-6703-7762; Paterson, Andrew/0000-0002-9169-118X; Melle, Ingrid /0000-0002-9783-548X; Schumacher, Johannes/0000-0001-9217-6457; Ruderfer, Douglas/0000-0002-2365-386X; Bruggeman, Richard/0000-0002-3238-8471; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Oliveira, Guiomar/0000-0002-7049-1277; Yu, Timothy/0000-0003-2988-7701; Thapar, Anita/0000-0002-3689-737X; Etain, Bruno/0000-0002-5377-1488; de Geus, Eco/0000-0001-6022-2666; Cormand, Bru/0000-0001-5318-4382; Betancur, Catalina/0000-0002-3327-4804; Backlund, Lena/0000-0001-9399-5024; Gallagher, Louise/0000-0001-9462-2836; Zammit, Stanley/0000-0002-2647-9211; Myin-Germeys, Inez/0000-0002-3731-4930; Jamain, Stephane/0000-0002-4321-4100; Greenwood, Tiffany/0000-0002-6080-6503; Kent, Lindsey/0000-0002-5315-3399; Anney, Richard/0000-0002-6083-407X; Lee, Sang Hong/0000-0001-9701-2718; Lencz, Todd/0000-0001-8586-338X; McQuillin, Andrew/0000-0003-1567-2240; Lesch, Klaus-Peter/0000-0001-8348-153X; Hamilton, Steven/0000-0001-8106-6260; Bergen, Sarah/0000-0002-5888-0034; Anttila, Verneri/0000-0002-0073-4675; McMahon, Francis/0000-0002-9469-305X FU National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London; Maudsley NHS Foundation Trust; King's College London; US National Institute of Mental Health (NIMH) [K99MH101367]; NIMH [U01 MH085520]; Netherlands Scientific Organization (NOW) [480-05-003]; Dutch Brain Foundation; VU University FX G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. The PGC Cross-Disorder Group is supported by NIMH grant U01 MH085520. Statistical analyses were carried out on the Genetic Cluster Computer, which is fmancially supported by the Netherlands Scientific Organization (NOW; 480-05-003; principal investigator D.P.) along with a supplement from the Dutch Brain Foundation and VU University. Numerous (> 100) grants from government agencies along with substantial private and foundation support worldwide enabled the collection of phenotype and genotype data, without which this research would not be possible. NR 39 TC 110 Z9 111 U1 20 U2 126 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 FEB PY 2015 VL 18 IS 2 BP 199 EP 209 DI 10.1038/nn.3922 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CA0UM UT WOS:000348631800010 ER PT J AU Reardon, DA Wen, PY AF Reardon, David A. Wen, Patrick Y. TI GLIOMA IN 2014 Unravelling tumour heterogeneity -implications for therapy SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID NEWLY-DIAGNOSED GLIOBLASTOMA; BEVACIZUMAB; TEMOZOLOMIDE; TRIAL; IDH1 AB Heterogeneity within and across tumours is increasingly recognized as a critical factor that limits therapeutic progress for many cancers. Key studies reported in 2014 describe previously unappreciated patterns of geographical and temporal heterogeneity for glioblastoma (the mostcommon primary CNS tumour in adults), with important implications for ongoing therapeutic studies evaluating molecular targeted therapies. C1 [Reardon, David A.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA. RP Reardon, DA (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. EM david_reardon@dfci.harvard.edu NR 10 TC 22 Z9 25 U1 0 U2 4 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 FEB PY 2015 VL 12 IS 2 BP 69 EP 70 DI 10.1038/nrclinonc.2014.223 PG 2 WC Oncology SC Oncology GA CA4GB UT WOS:000348861300002 PM 25560529 ER PT J AU Smith, TR Habib, A Rosenow, JM Nahed, BV Babu, MA Cybulski, G Fessler, R Batjer, HH Heary, RF AF Smith, Timothy R. Habib, Ali Rosenow, Joshua M. Nahed, Brian V. Babu, Maya A. Cybulski, George Fessler, Richard Batjer, H. Hunt Heary, Robert F. TI Defensive Medicine in Neurosurgery: Does State-Level Liability Risk Matter? SO NEUROSURGERY LA English DT Article DE Defensive medicine; Health reform; Liability; Malpractice; Neurosurgery; Tort ID MALPRACTICE LITIGATION; PHYSICIANS; CLAIMS; REFORM; DOCTORS; LAW; SUE AB BACKGROUND: Defensive medicine is prevalent among US neurosurgeons due to the high risk of malpractice claims. This study provides national estimates of US neurosurgeons' defensive behaviors and perceptions. OBJECTIVE: To examine the relationship of defensive medicine-both "assurance" behaviors and "avoidance" behaviors-to the liability environment. METHODS: A 51-question online survey was sent to 3344 US neurosurgeon members of the American Board of Neurological Surgeons (ABNS). The survey was anonymous and conducted over 6 weeks in the spring of 2011. The previously validated questionnaire contained questions on neurosurgeon, patient, and practice characteristics; perceptions of the liability environment; and defensive-medicine behaviors. Bivariate and multivariate analyses examined the state liability risk environment as a predictor of a neurosurgeon's likelihood of practicing defensive medicine. RESULTS: A total of 1026 neurosurgeons completed the survey (31% response rate). Neurosurgeons' perceptions of their state's liability environment generally corresponded well to more objective measures of state-level liability risk because 83% of respondents correctly identified that they were practicing in a high-risk environment. When controlling for surgeon experience, income, high-risk patient load, liability history, and type of patient insurance, neurosurgeons were 50% more likely to practice defensive medicine in high-risk states compared with low-risk-risk states (odds ratio: 1.5, P < .05). CONCLUSION: Both avoidance and assurance behaviors are prevalent among US neurosurgeons and are correlated with subjective and objective measures of state-level liability risk. Defensive medicine practices do not align with patient-centered care and may contribute to increased inefficiency in an already taxed health care system. C1 [Smith, Timothy R.; Habib, Ali; Rosenow, Joshua M.; Cybulski, George; Fessler, Richard; Batjer, H. Hunt] Northwestern Univ, Dept Neurol Surg, Chicago, IL 60611 USA. [Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Babu, Maya A.] Mayo Clin & Mayo Grad Sch Med, Dept Neurol Surg, Rochester, MN USA. [Heary, Robert F.] UMDNJ New Jersey Med Sch, Dept Neurol Surg, Newark, NJ USA. RP Smith, TR (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Neurol Surg, 676 N St Clair St,Suite 2210, Chicago, IL 60611 USA. EM timothy-smith-0@fsm.northwestern.edu FU Congress of Neurological Surgeons; Council of State Neurosurgical Societies FX The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. Sources of funding were the Congress of Neurological Surgeons and the Council of State Neurosurgical Societies. NR 28 TC 10 Z9 10 U1 0 U2 4 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 FEB PY 2015 VL 76 IS 2 BP 105 EP 113 DI 10.1227/NEU.0000000000000576 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AZ3SR UT WOS:000348147500017 PM 25255258 ER PT J AU Torriani, M Oliveira, AL Azevedo, DC Bredella, MA Yu, EW AF Torriani, Martin Oliveira, Adriana L. Azevedo, Debora C. Bredella, Miriam A. Yu, Elaine W. TI Effects of Roux-en-Y Gastric Bypass Surgery on Visceral and Subcutaneous Fat Density by Computed Tomography SO OBESITY SURGERY LA English DT Article DE Obesity; Adipose tissue; Metabolic syndrome; Visceral fat; Surgery; Computed tomography ID ADIPOSE-TISSUE; SYSTEMIC INFLAMMATION; SLEEVE GASTRECTOMY; EVOLUTION; RISK AB We aimed to test the hypothesis that noninvasive fat density by computed tomography (CT) increases after Roux-en-Y gastric bypass (RYGB) and correlates with improved cardiometabolic risk. We examined 21 obese adults before and 12 months after RYGB and 16 obese nonsurgical controls followed for 12 months. Visceral (VAT) and subcutaneous adipose tissue (SAT) density increased after RYGB (P < 0.0001) while remaining stable in controls (P a parts per thousand yenaEuro parts per thousand 0.1). In RYGB subjects, 12-month increase in VAT density correlated with decreased C-reactive protein (CRP) independent of change in VAT area or BMI (both P < 0.05). Twelve-month increase in SAT density correlated with increased HDL cholesterol independent of change in SAT area (P = 0.048), BMI (P = 0.03), or statin use (P = 0.002), and 1 unit increase in SAT density had increased odds of higher total abdominal fat loss (P = 0.002). C1 [Torriani, Martin; Oliveira, Adriana L.; Azevedo, Debora C.; Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Torriani, Martin; Oliveira, Adriana L.; Azevedo, Debora C.; Bredella, Miriam A.; Yu, Elaine W.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yu, Elaine W.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM mtorriani@mgh.harvard.edu FU National Institutes of Health [HD51959, RR025758, DK093713] FX This study was funded by the National Institutes of Health (Grant Numbers: HD51959, RR025758 and DK093713). NR 10 TC 7 Z9 7 U1 0 U2 1 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 FEB PY 2015 VL 25 IS 2 BP 381 EP 385 DI 10.1007/s11695-014-1485-6 PG 5 WC Surgery SC Surgery GA AZ3ER UT WOS:000348111000029 PM 25381117 ER PT J AU Papakostas, TD Le, HG Chodosh, J Jacobs, DS AF Papakostas, Thanos D. Le, Hong-Gam Chodosh, James Jacobs, Deborah S. TI Prosthetic Replacement of the Ocular Surface Ecosystem as Treatment for Ocular Surface Disease in Patients with a History of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis SO OPHTHALMOLOGY LA English DT Article ID COST-EFFECTIVENESS THRESHOLD; SCLERAL CONTACT-LENS; VERSUS-HOST-DISEASE; BOSTON KERATOPROSTHESIS; ERYTHEMA MULTIFORME; MANIFESTATIONS; MANAGEMENT; THERAPY; COMPLICATIONS; NICE AB Purpose: To report the visual outcomes of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in patients with ocular surface disease related to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Design: Retrospective cohort study. Subjects: We included 86 patients (167 eyes) with history of SJS/TEN who underwent PROSE treatment from January 1, 2006, to January 1, 2011. Methods: Etiology, previous interventions, change in visual acuity, change in visual function, and duration of follow-up are reported. Paired t test and Friedman test with Dunn's post hoc test for multiple comparisons were used for statistical analysis. Main Outcome Measures: Visual acuity at last follow-up and visual function based on the National Eye Institute 25-item Visual Functioning Questionnaire (NEI VFQ-25) at 6 months. Results: We treated 35 males and 51 females with a history of SJS/TENS; median age was 36 years. The most common reported etiologies for SJS/TENS were antibiotics (n = 25), ibuprofen (n = 15), and lamotrigine (n = 11). The median visual acuity at the initial visit was 20/60 (range, 20/400-20/25; 0.48 logarithm of the minimum angle of resolution [logMAR]), and the visual acuity at completion of customization was 20/25 (range, 20/200-20/20; 0.096 logMAR; P < 0.001), with no decline in median acuity at the end of follow-up. Median duration of follow-up was 16 months. There was a significant improvement in the visual function of the patients based on the NEI VFQ-25 questionnaire (mean of 48 points at baseline vs. mean of 72 points at 6 months; P < 0.001). In addition, there was also an improvement in the self-reported general health of the patients (mean of 57 points at baseline vs. mean of 65 points at 6 months; P < 0.01). Conclusions: In a large cohort of patients with chronic ocular surface disease related to SJS/TEN, PROSE treatment offers sustained and significant large improvement in visual function and acuity. (C) 2015 by the American Academy of Ophthalmology. C1 [Papakostas, Thanos D.; Chodosh, James; Jacobs, Deborah S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Le, Hong-Gam; Jacobs, Deborah S.] Boston Fdn Sight, Needham, MA 02494 USA. RP Jacobs, DS (reprint author), Boston Fdn Sight, 464 Hillside Ave,Suite 205, Needham, MA 02494 USA. EM djacobs@bostonsight.org NR 28 TC 8 Z9 8 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2015 VL 122 IS 2 BP 248 EP 253 DI 10.1016/j.ophtha.2014.08.015 PG 6 WC Ophthalmology SC Ophthalmology GA AZ5WT UT WOS:000348290000015 PM 25282251 ER PT J AU Qian, CX Hassanaly, S Harissi-Dagher, M AF Qian, Cynthia X. Hassanaly, Salima Harissi-Dagher, Mona TI Anterior Segment Optical Coherence Tomography in the Long-Term Follow-up and Detection of Glaucoma in Boston Type I Keratoprosthesis SO OPHTHALMOLOGY LA English DT Article ID UNIVERSITY-OF-CALIFORNIA; CHAMBER ANGLE ASSESSMENT; ULTRASOUND BIOMICROSCOPY; OUTCOMES; ENDOPHTHALMITIS; COMPLICATIONS; MULTICENTER; PREVENTION; RESOLUTION; INFECTION AB Purpose: To evaluate the role of anterior segment (AS) optical coherence tomography (OCT) as a standardized method of imaging Boston type I keratoprosthesis (KPro) after surgery, particularly in the visualization of iris and angle structures. Design: Prospective case series. Participants: Twenty patients who underwent KPro implantation in 1 eye. Methods: Patients underwent AS OCT imaging before surgery. After KPro implantation, patients were imaged using the AS single, dual, and quad scans to obtain transverse images of the eye every 15 degrees over 360 degrees. High-resolution, corneal quad, and anterior chamber scans were also obtained. This imaging protocol allowed juxtaposition and comparison of the same imaging coordinates obtained before surgery and 3, 6, and 12 months after surgery. Main Outcome Measures: Postoperative visual acuity (VA), glaucoma progression on clinical examination and formal visual field testing, and anatomic angle changes on AS OCT defined by angle closure, peripheral anterior synechiae (PAS), iriseKPro backplate touch, and graftehost interface changes over time. Results: Mean follow-up was 18.8 +/- 3.2 months. The average preoperative VA was 1.9 +/- 0.5 logarithm of the minimum angle of resolution. After surgery, VA improved to 1.0 +/- 0.9 at last follow-up (P = 0.002). Fourteen of 20 patients had glaucoma before surgery. After surgery, 5 of these patients deteriorated clinically and 1 de novo diagnosis of glaucoma was made. On OCT, the average total degrees of angle closure for all patients increased from 158.5 +/- 158.9 degrees before surgery to 205.4 +/- 154.0 degrees after surgery (P = 0.04). The number of eyes with 360 degrees of PAS increased from 6 of 20 before surgery to 9 of 20 after surgery. Irisebackplate touch was demonstrated in 5 of 20 patients, with an average area of involvement of 24.2 +/- 36.2 degrees. Overall, of the 12 of 20 patients with clear signs of anatomic angle narrowing and synechiae progression on imaging, 3 had glaucoma deterioration detected by clinical examination. In the other 9 patients, angle changes on OCT were not accompanied by any detectable clinical signs of glaucomatous deterioration. Conclusions: Anterior segment OCT can be used to observe anatomic changes after KPro implantation that cannot be detected otherwise. We were unable to demonstrate a correlation between anatomic features and clinical progression. (C) 2015 by the American Academy of Ophthalmology. C1 [Qian, Cynthia X.; Hassanaly, Salima; Harissi-Dagher, Mona] Univ Montreal, Dept Ophthalmol, Quebec City, PQ, Canada. [Qian, Cynthia X.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Harissi-Dagher, M (reprint author), CHUM, Hop Notre Dame, 1560 Sherbrooke E, Montreal, PQ H2L 4M1, Canada. EM monadagher@hotmail.com FU Pfizer Investigator-Initiated Research program; American Society of Cataract and Refractive Surgery research grant; Fonds de Recherche en Ophtalmologie de l'Universite de Montreal, Montreal, Canada FX Supported by the Pfizer Investigator-Initiated Research program; an American Society of Cataract and Refractive Surgery research grant; and a research grant from the Fonds de Recherche en Ophtalmologie de l'Universite de Montreal, Montreal, Canada. The sponsor or funding organization had no role in the design or conduct of this research. NR 35 TC 6 Z9 6 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2015 VL 122 IS 2 BP 317 EP 325 DI 10.1016/j.ophtha.2014.08.007 PG 9 WC Ophthalmology SC Ophthalmology GA AZ5WT UT WOS:000348290000024 PM 25264027 ER PT J AU Ip, MS Domalpally, A Sun, JK Ehrlich, JS AF Ip, Michael S. Domalpally, Amitha Sun, Jennifer K. Ehrlich, Jason S. TI Long-term Effects of Therapy with Ranibizumab on Diabetic Retinopathy Severity and Baseline Risk Factors for Worsening Retinopathy SO OPHTHALMOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MACULAR EDEMA; FOCAL/GRID PHOTOCOAGULATION; INTRAVITREAL TRIAMCINOLONE; PROLIFERATIVE RETINOPATHY; CLINICAL-TRIAL; PROGRESSION; COMPLICATIONS; CANDESARTAN; ACETONIDE AB Purpose: To assess the effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity when administered for up to 3 years, evaluate the effect of delayed initiation of ranibizumab therapy on DR severity, and identify baseline patient characteristics associated with the development of proliferative DR (PDR). Design: Exploratory analyses of phase III, randomized, double-masked, sham-controlled multicenter clinical trials. Participants: Adults with diabetic macular edema (DME) (N = 759), baseline best-corrected visual acuity 20/40 to 20/320 Snellen equivalent, and central foveal thickness >= 275 mu m. Methods: Patients were randomized to monthly 0.3 or 0.5 mg ranibizumab or sham injections. Sham participants could switch to 0.5 mg ranibizumab during the third year (sham/0.5 mg crossover). Baseline risk factors were evaluated to explore potential associations with development of PDR. Time to first development of PDR was analyzed by Kaplan-Meier methods to calculate cumulative probabilities by group. Main Outcome Measures: Study eye change on the Early Treatment Diabetic Retinopathy Study severity scale and a composite clinical outcome evaluating progression to PDR based on photographic changes plus clinically important events defining PDR. Results: At month 36, a greater proportion of ranibizumab-treated eyes had >= 2- or >= 3-step DR improvement compared with sham/0.5 mg crossover. A >= 3-step improvement was achieved at 36 months by 3.3%, 15.0%, and 13.2% of sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab-treated eyes, respectively (P < 0.0001). Through 36 months, 39.1% of eyes in the sham/0.5 mg group developed PDR, as measured by composite outcome, compared with 18.3% and 17.1% of eyes treated with 0.3 or 0.5 mg ranibizumab, respectively. The presence of macular capillary nonperfusion at baseline seems to be associated with progression to PDR in ranibizumab-treated eyes but did not meaningfully influence visual acuity improvement in eyes with DME after ranibizumab therapy. Conclusions: Ranibizumab, as administered to patients with DME for 12 to 36 months in these studies, can both improve DR severity and prevent worsening. Prolonged delays in initiation of ranibizumab therapy may limit this therapeutic effect. Although uncommon, the development of PDR still occurs in a small percentage of eyes undergoing antievascular endothelial growth factor therapy and may be related to the presence of macular nonperfusion. (C) 2015 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). C1 [Ip, Michael S.; Domalpally, Amitha] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med, Madison, WI 53717 USA. [Sun, Jennifer K.] Joslin Diabet Ctr, Harvard Dept Ophthalmol, Boston, MA 02215 USA. [Ehrlich, Jason S.] Genentech Inc, San Francisco, CA 94080 USA. RP Ip, MS (reprint author), Univ Wisconsin, Fundus Photograph Reading Ctr, 8010 Excelsior Dr,Suite 100, Madison, WI 53717 USA. EM msip@wisc.edu RI Dagdelen, Selcuk /A-9432-2017 FU Allergan Inc.; Optovue; Genentech, Inc.; Boston Micromachines FX The author(s) have made the following disclosure(s): M.S.I.: Consultant/advisor - Eye Technology Ltd, Genentech, Inc., NicOx, Notal Vision, QLT Phototherapeutics Inc., Regeneron, Sirion; Grant support - Allergan Inc. J.S.: Consultant - Novartis; Scientific Advisory Board - Abbott Laboratories; Research support - Optovue, Genentech, Inc., Boston Micromachines. J.S.E.:Employee - Genentech, Inc. (a member of the Roche Group); Equity and/or options - Roche. Supported by Genentech, Inc.; Support for third-party writing assistance was provided by Genentech, Inc. The sponsor participated in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation and review of the manuscript. NR 25 TC 20 Z9 21 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2015 VL 122 IS 2 BP 367 EP 374 DI 10.1016/j.ophtha.2014.08.048 PG 8 WC Ophthalmology SC Ophthalmology GA AZ5WT UT WOS:000348290000029 PM 25439595 ER PT J AU Manze, MG Orner, MB Glickman, M Pbert, L Berlowitz, D Kressin, NR AF Manze, Meredith G. Orner, Michelle B. Glickman, Mark Pbert, Lori Berlowitz, Dan Kressin, Nancy R. TI Brief provider communication skills training fails to impact patient hypertension outcomes SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Hypertension; Blood pressure; Patient-provider communication; Medication adherence; Patient-centered care ID BLOOD-PRESSURE CONTROL; WORCESTER-AREA TRIAL; PRIMARY-CARE; HYPERLIPIDEMIA WATCH; GENDER CONCORDANCE; PHYSICIAN; ADHERENCE; INTERVENTION; MANAGEMENT; SUPPORT AB Objectives: Hypertension remains a prevalent risk factor for cardiovascular disease, and improved medication adherence leads to better blood pressure (BP) control. We sought to improve medication adherence and hypertension outcomes among patients with uncontrolled BP through communication skills training targeting providers. Methods: We conducted a randomized controlled trial to assess the effects of a communication skills intervention for primary care doctors compared to usual care controls, on the outcomes of BP (systolic, diastolic), patient self-reported medication adherence, and provider counseling, assessed at baseline and post-intervention. We enrolled 379 patients with uncontrolled BP; 203 (54%) with follow-up data comprised our final sample. We performed random effects least squares regression analyses to examine whether the provider training improved outcomes, using clinics as the unit of randomization. Results: In neither unadjusted nor multivariate analyses were significant differences in change detected from baseline to follow-up in provider counseling, medication adherence or BP, for the intervention versus control groups. Conclusion: The intervention did not improve the outcomes; it may have been too brief and lacked sufficient practice level changes to impact counseling, adherence or BP. Practice Implications: Future intervention efforts may require more extensive provider training, along with broader systematic changes, to improve patient outcomes. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Manze, Meredith G.] CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10035 USA. [Orner, Michelle B.; Glickman, Mark; Berlowitz, Dan] Bedford VAMC, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Glickman, Mark; Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Hlth Policy & Management Dept, Boston, MA USA. [Pbert, Lori] Univ Massachusetts, Sch Med, Worcester, MA USA. [Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Manze, MG (reprint author), CUNY Hunter Coll, Sch Publ Hlth, 2180 3rd Ave,Room 523, New York, NY 10035 USA. EM meredith.manze@hunter.cuny.edu FU NIH/National Heart, Lung, and Blood Institute [R01 HL072814]; Health Services Research and Development Service, Department of Veterans Affairs [RCS 02-066-1] FX This study was supported by NIH/National Heart, Lung, and Blood Institute grant R01 HL072814 (PI: Kressin); Dr Kressin is also supported by a Senior Research Career Scientist award (RCS 02-066-1) from the Health Services Research and Development Service, Department of Veterans Affairs. We thank Peter Davidson, MD, and the clinic and research staff for their assistance. NR 34 TC 1 Z9 1 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD FEB PY 2015 VL 98 IS 2 BP 191 EP 198 DI 10.1016/j.pec.2014.10.014 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AZ9SL UT WOS:000348555400010 PM 25468397 ER PT J AU Linsky, A Simon, SR Bokhour, B AF Linsky, Amy Simon, Steven R. Bokhour, Barbara TI Patient perceptions of proactive medication discontinuation SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Patient beliefs; Communication; Shared decision making; Medication safety ID DECISION-MAKING; RANDOMIZED-TRIAL; HEALTH BELIEFS; OLDER-ADULTS; PREFERENCES; ADHERENCE; POLYPHARMACY; CARE AB Objective: While many patients prefer fewer medications, decisions about medication discontinuation involve collaboration between patients and providers. We sought to identify patient perspectives on intentional medication discontinuation in order to optimize medication use. Methods: We conducted 20 interviews and two focus groups with a convenience sample of patients (22 men, 5 women; mean age 66 years) at two US Veterans Affairs Medical Centers. We queried patients' experiences with and attitudes toward taking multiple medications, preferences about taking fewer medications, and communication with their providers about stopping a medicine. Transcripts were analyzed qualitatively. Results: Three main themes emerged to create a conceptual model of medication discontinuation from the patient perspective: (1) conflicting views of medication, encompassing the sub-themes of desire for fewer medications, adherence, and specific versus general; (2) importance of patient-provider relationships, encompassing the sub-themes of trust, relying on expertise, shared decision making, and balancing multiple providers; and (3) limited experience with medication discontinuation. Conclusion: Many patients who have a preference to take fewer medicines do not share their beliefs with providers and recall few instances of provider-initiated medication discontinuation. Practice implications: Strengthening patient-provider relationships and eliciting patient attitudes about taking fewer medications may enable appropriate discontinuation of unnecessary medications. Published by Elsevier Ireland Ltd. C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA. [Linsky, Amy; Simon, Steven R.; Bokhour, Barbara] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. [Linsky, Amy; Simon, Steven R.; Bokhour, Barbara] ENRM Vet Affairs Med Ctr, Boston, MA USA. [Linsky, Amy; Simon, Steven R.; Bokhour, Barbara] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Linsky, Amy; Simon, Steven R.; Bokhour, Barbara] ENRM Vet Affairs Med Ctr, Bedford, MA USA. [Linsky, Amy; Simon, Steven R.] Boston Med Ctr, Gen Internal Med Sect, Boston, MA USA. [Linsky, Amy; Simon, Steven R.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Bokhour, Barbara] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Linsky, A (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,Bldg 9,Room 425 152G, Boston, MA 02130 USA. EM AmylinsIcy@va.gov; Steven.Simon2@va.gov; Barbara.Bokhour@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Career Development Award FX We thank Thomas Marcello, BA and Justice Clark, BA for their assistance in the coordination and assistance with research activities. We confirm all patient/personal identifiers have been removed or disguised so the patient/person(s) described are not identifiable and cannot be identified through the details of the story. The study was conducted using resources of the VA Boston Healthcare System. The PI was supported by a Department of Veterans Affairs, Veterans Health Administration, Career Development Award. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; nor decision to submit the manuscript for publication. NR 31 TC 9 Z9 9 U1 2 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD FEB PY 2015 VL 98 IS 2 BP 220 EP 225 DI 10.1016/j.pec.2014.11.010 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AZ9SL UT WOS:000348555400014 PM 25435516 ER PT J AU Chang, CY Huang, AJ Palmer, WE AF Chang, Connie Y. Huang, Ambrose J. Palmer, William E. TI Radiographic Evaluation of Hip Implants SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY LA English DT Article DE hip arthroplasty; radiograph; evaluation ID METAL-ON-METAL; PERIPROSTHETIC FEMORAL FRACTURES; RESURFACING ARTHROPLASTY; VANCOUVER CLASSIFICATION; ILIOPSOAS IMPINGEMENT; ACETABULAR COMPONENT; SURFACE ARTHROPLASTY; REPLACEMENT; REVISION; DISLOCATION AB Serial radiographs are the mainstay in the longitudinal assessment of hip implants. The prosthesis, periprosthetic bone, and juxta-articular soft tissues are inspected for fracture, periosteal reaction, stress shielding, calcar resorption, osteolysis, bony remodeling, metallic debris, and heterotopic ossification. Comparison radiographs best confirm implant migration, subsidence, and aseptic loosening. Infection, particle disease, reaction to metal, and mechanical impingement are important causes of postsurgical pain, but in their earliest stages they may be difficult to diagnose using radiographs. This article addresses the role of radiography following hip arthroplasty. C1 [Chang, Connie Y.; Huang, Ambrose J.; Palmer, William E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. RP Chang, CY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM cychang@mgh.harvard.edu NR 70 TC 3 Z9 3 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1089-7860 EI 1098-898X J9 SEMIN MUSCULOSKEL R JI Semin. Musculoskelet. Radiol. PD FEB PY 2015 VL 19 IS 1 BP 12 EP 20 DI 10.1055/s-0034-1396763 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CA3IE UT WOS:000348799000003 PM 25633021 ER PT J AU Tucker, JD Gelpi, A Bangsberg, DR Grewe, ME Necochea, R AF Tucker, Joseph D. Gelpi, Adriane Bangsberg, David R. Grewe, Mary E. Necochea, Raul TI The disruptive influence of syphilis cures within specialist venereal systems: implications for HIV cure preparedness SO SEXUALLY TRANSMITTED INFECTIONS LA English DT Editorial Material C1 [Tucker, Joseph D.] Int Diagnost Ctr, London WC1E 7HT, England. [Tucker, Joseph D.; Gelpi, Adriane; Grewe, Mary E.] Univ N Carolina, Inst Global Hlth & Infect Dis, Chapel Hill, NC USA. [Gelpi, Adriane; Grewe, Mary E.; Necochea, Raul] Univ N Carolina, Dept Social Med, Chapel Hill, NC USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Tucker, JD (reprint author), Int Diagnost Ctr, Keppel St, London WC1E 7HT, England. EM joseph.tucker@post.harvard.edu FU NIAID NIH HHS [R01 AI108366, P30 AI050410]; PHS HHS [NIAID R01A108366-01, NIAID P30-AI50410] NR 10 TC 1 Z9 1 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1368-4973 EI 1472-3263 J9 SEX TRANSM INFECT JI Sex. Transm. Infect. PD FEB PY 2015 VL 91 IS 1 BP 2 EP 3 DI 10.1136/sextrans-2014-051777 PG 2 WC Infectious Diseases SC Infectious Diseases GA AZ5SH UT WOS:000348279500001 PM 25609463 ER PT J AU Koffel, EA Koffel, JB Gehrman, PR AF Koffel, Erin A. Koffel, Jonathan B. Gehrman, Philip R. TI A meta-analysis of group cognitive behavioral therapy for insomnia SO SLEEP MEDICINE REVIEWS LA English DT Review DE Group therapy; CBT-I; Insomnia ID RANDOMIZED CONTROLLED-TRIAL; PSYCHIATRIC-DISORDERS; PERSISTENT INSOMNIA; SLEEP DISTURBANCE; STEPPED CARE; OLDER-ADULTS; EFFICACY; INTERVENTION; SEVERITY; DISEASE AB Insomnia is the most common sleep disorder among the general population. Although cognitive behavioral therapy for insomnia (CBT-I) is the psychological treatment of choice, the availability of individual therapy is often not sufficient to meet the demand for treatment. Group treatment can increase the efficiency of delivery, but its efficacy has not been well-established. Randomized controlled trials (RCfs) comparing group CBT-I to a control group in patients with insomnia were identified. A review of 670 unique citations resulted in eight studies that met criteria for analysis. Outcome variables included both qualitative (e.g., sleep quality) and quantitative (e.g., sleep diary) outcomes, as well as depression and pain severity, at both pre- to post-treatment and follow-up (3-12 mo post-treatment). Overall, we found medium to large effect sizes for sleep onset latency, sleep efficiency, and wake after sleep onset and small effect sizes for pain outcomes. Effect sizes remained significant at follow-up, suggesting that treatment gains persist over time. Other variables, including total sleep time, sleep quality, and depression, showed significant improvements, but these findings were limited to the within treatment group analyses. It is clear that group CBT-I is an efficacious treatment. Implications for stepped care models for insomnia are discussed. Published by Elsevier Ltd. C1 [Koffel, Erin A.] Univ Minnesota, Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA. [Koffel, Erin A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Koffel, Jonathan B.] Univ Minnesota, Biomed Lib, Minneapolis, MN USA. [Gehrman, Philip R.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Gehrman, Philip R.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Koffel, EA (reprint author), Dept Vet Affairs Med Ctr, 1 Vet Dr, Minneapolis, MN 55417 USA. EM Erin.Koffel@va.gov OI Koffel, Jonathan/0000-0003-1723-5087 FU VA [VA999999] NR 46 TC 23 Z9 24 U1 8 U2 33 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1087-0792 EI 1532-2955 J9 SLEEP MED REV JI Sleep Med. Rev. PD FEB PY 2015 VL 19 BP 6 EP 16 DI 10.1016/j.smrv.2014.05.001 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AZ6NP UT WOS:000348336600003 PM 24931811 ER PT J AU Sonis, S Elting, L Keefe, D Nguyen, H Grunberg, S Randolph-Jackson, P Brennan, M AF Sonis, Stephen Elting, Linda Keefe, Dorothy Nguyen, Hoang Grunberg, Steven Randolph-Jackson, Pamela Brennan, Michael CA TRIAD Burden Illness Investigators TI Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Head and neck cancerd; Non-small cell lung cancer; Radiotherapy; Diarrhea ID LOCALLY ADVANCED HEAD; CONCOMITANT CISPLATIN; RADIOTHERAPY; CHEMOTHERAPY; MUCOSITIS; CONCURRENT AB To better understand the indirect effects of standard courses of radiation therapy (RT) on distant tissue toxicity, we evaluated the frequency, course, and health and economic burden of regimen-related diarrhea in a large, multinational group of patients who were being treated for cancers of the head and neck (HNC) or lung (NSCLC). In this exploratory, prospective study, 284 patients being treated for HNC and 60 being treated for NSCLC were stratified into four cohorts to evaluate the effect of radiation alone and radiation plus concomitant chemotherapy (CRT) on radiation-induced diarrhea (RID). RID was assessed daily throughout RT using a patient-reported five-point categorical scale. Health and resource use outcomes were evaluated at least weekly during radiation. Moderate to severe RID was reported in all groups and was worse among patient being treated with concomitant chemoradiation (CRT). Whereas 29 % of patients treated with radiation only developed RID, the incidence was 42 % among CRT-treated patients. Tumor site did not impact the rate of RID, but did impact the rate of development and was more acute in patients being treated for NSCLC than for HNC. Patients with significant RID had worse health and resource use outcomes than did patients without RID regardless of the form of treatment. G-tube placement, weight loss, unplanned office visits, and in-patient days were adversely affected by RID. Not surprisingly, patients treated with CRT had poorer health and resource outcomes than RT only patients, even in the absence of RID. In addition to local tissue toxicities, our results suggest that focal radiation may also be associated with significant distant tissue-centric injury here represented by RID. While these changes were seen with radiation alone, the addition of chemotherapy increased the incidence and burden of illness. RID adversely impacted resource use. This unanticipated finding supports the hypothesis that focal radiation therapy results in pathobiological changes that extend beyond the radiation field and which can produce distant changes. C1 [Sonis, Stephen] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sonis, Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Elting, Linda; Nguyen, Hoang] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Keefe, Dorothy] Univ Adelaide, Adelaide, SA, Australia. [Grunberg, Steven] Univ Vermont, Med Ctr, Burlington, VT USA. [Randolph-Jackson, Pamela] MedStar Washington Hosp Ctr, Washington, DC USA. [Brennan, Michael] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Sonis, Stephen] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. RP Sonis, S (reprint author), Brigham & Womens Hosp, Div Oral Med, 75 Francis St, Boston, MA 02115 USA. EM ssonis@partners.org FU Helsinn, Inc. FX This study was supported by an unrestricted grant from Helsinn, Inc. NR 18 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD FEB PY 2015 VL 23 IS 2 BP 433 EP 439 DI 10.1007/s00520-014-2395-9 PG 7 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA AZ6AB UT WOS:000348298700019 PM 25123194 ER PT J AU Antebi, B Zhang, ZL Wang, Y Lu, ZD Chen, XD Ling, J AF Antebi, Ben Zhang, ZhiLiang Wang, Yu Lu, ZhongDing Chen, Xiao-Dong Ling, Jian TI Stromal-Cell-Derived Extracellular Matrix Promotes the Proliferation and Retains the Osteogenic Differentiation Capacity of Mesenchymal Stem Cells on Three-Dimensional Scaffolds SO Tissue Engineering Part C-Methods LA English DT Article ID PERFUSION BIOREACTOR SYSTEM; BONE-MARROW-CELLS; IN-VITRO; EX-VIVO; CONSTRUCT DEVELOPMENT; SEEDING DENSITY; SELF-RENEWAL; CULTURE; NICHE; MICROENVIRONMENT AB To date, expansion of bone-marrow-derived mesenchymal stem cells (MSCs) is typically carried out on two-dimensional (2D) tissue culture plastic. Since this 2D substratum is very different from the physiological situation, MSCs gradually lose their unique multipotent properties during expansion. Recently, the role of the extracellular matrix (ECM) microenvironment ("niche") in facilitating and regulating stem cell behavior in vivo has been elucidated. As a result, investigators have shifted their efforts toward developing three-dimensional (3D) scaffolds capable of functioning like the native tissue ECM. In this study, we demonstrated that stromal-cell-derived ECM, formed within a collagen/hydroxyapatite (Col/HA) scaffold to mimic the bone marrow "niche," promoted MSC proliferation and preserved their differentiation capacity. The ECM was synthesized by MSCs to reconstitute the tissue-specific 3D microenvironment in vitro. Following deposition of the ECM inside Col/HA scaffold, the construct was decellularized and reseeded with MSCs to study their behavior. The data showed that MSCs cultured on the ECM-Col/HA scaffolds grew significantly faster than the cells from the same batch cultured on the regular Col/HA scaffolds. In addition, MSCs cultured on the ECM-Col/HA scaffolds retained their "stemness" and osteogenic differentiation capacity better than MSCs cultured on regular Col/HA scaffolds. When ECM-Col/HA scaffolds were implanted into immunocompromised mice, with or without loading MSCs, it was found that those scaffolds formed less bone as compared with regular Col/HA scaffolds (i.e., without ECM), in both cases of with or without loading MSCs. The in vivo study further confirmed that the ECM-Col/HA scaffold was a suitable mimic of the bone marrow "niche." This novel 3D stromal-cell-derived ECM system has the potential to be developed into a biomedical platform for regenerative medicine applications. C1 [Antebi, Ben; Ling, Jian] SW Res Inst, Microencapsulat & Nanomat Dept, San Antonio, TX 78238 USA. [Antebi, Ben; Ling, Jian] Univ Texas Hlth Sci Ctr San Antonio, Univ Texas San Antonio, Biomed Engn Program, San Antonio, TX 78229 USA. [Zhang, ZhiLiang; Wang, Yu; Lu, ZhongDing; Chen, Xiao-Dong] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Chen, Xiao-Dong] South Texas Vet Hlth Care Syst, Audie L Murphy Div Hosp, San Antonio, TX USA. RP Ling, J (reprint author), SW Res Inst, Microencapsulat & Nanomat Dept, 6220 Culebra Rd, San Antonio, TX 78238 USA. EM chenx4@uthscsa.edu; jling@swri.org FU National Heart, Lung, and Blood Institute [R21 HL102775] FX This work was supported by the National Heart, Lung, and Blood Institute: R21 HL102775. NR 46 TC 6 Z9 6 U1 4 U2 15 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3384 EI 1937-3392 J9 TISSUE ENG PART C-ME JI Tissue Eng. Part C-Methods PD FEB 1 PY 2015 VL 21 IS 2 BP 171 EP 181 DI 10.1089/ten.tec.2014.0092 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CA6HR UT WOS:000349012400007 PM 24965227 ER PT J AU Peev, MP Chang, YC King, DR Yeh, DD Kaafarani, H Fagenholz, PJ De Moya, MA Velmahos, GC AF Peev, Miroslav P. Chang, Yuchiao King, David R. Yeh, Daniel D. Kaafarani, Haytham Fagenholz, Peter J. De Moya, Marc A. Velmahos, George C. TI Delayed Laparotomy After Selective Non-operative Management of Penetrating Abdominal Injuries SO WORLD JOURNAL OF SURGERY LA English DT Article ID GUNSHOT WOUNDS; ROUTINE LAPAROTOMY; TRAUMA CENTER; ABDOMEN; CONSERVATISM; STANDARD; STILL AB Main concern during the practice of selective non-operative management (SNOM) for abdominal stab wounds (SW) and gunshot wounds (GSW) is the potential for harm in patients who fail SNOM and receive a delayed laparotomy (DL). The aim of this study is to determine whether such patients suffer adverse sequelae because of delays in diagnosis and treatment when managed under a structured SNOM protocol. 190 patients underwent laparotomy after an abdominal GSW or SW (5/04-10/12). Patients taken to operation within 120 min of admission were included in the early laparotomy (EL) group (n =153, 80.5 %) and the remaining in the DL group (n =37, 19.5 %). Outcomes included mortality, hospital stay, and postoperative complications. The median time from hospital arrival to operation was 43 min (range: 17-119) for EL patients and 249 min (range: 122-1,545) for DL patients. The average number and type of injuries were similar among the groups. Mortality and negative laparotomy were observed only in the EL group. There was no significant difference in the hospital stay between the groups. The overall complications were higher in the EL group (44.4 vs. 24.3 %, p =0.026). DL was independently associated with a lower likelihood for complications (OR 0.39, 95 % CI 0.16-0.98, p =0.045). Individual review of all DL patients did not reveal an incident in which complications could be directly attributed to the delay. In a structured protocol, patients who fail SNOM and require an operation are recognized and treated promptly. The delay in operation does not cause unnecessary morbidity or mortality. C1 [Peev, Miroslav P.; Chang, Yuchiao; King, David R.; Yeh, Daniel D.; Kaafarani, Haytham; Fagenholz, Peter J.; De Moya, Marc A.; Velmahos, George C.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Peev, Miroslav P.; Chang, Yuchiao; King, David R.; Yeh, Daniel D.; Kaafarani, Haytham; Fagenholz, Peter J.; De Moya, Marc A.; Velmahos, George C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Peev, MP (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM miroslav.peev@tufts.edu; gvelmahos@mgh.harvard.edu OI King, David/0000-0003-1028-1478 NR 20 TC 3 Z9 3 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 FEB PY 2015 VL 39 IS 2 BP 380 EP 386 DI 10.1007/s00268-014-2813-7 PG 7 WC Surgery SC Surgery GA AZ4XK UT WOS:000348224100014 PM 25277981 ER PT J AU Chambers, KJ Pearse, A Coveney, J Rogers, S Kamani, D Sritharan, N Randolph, GW AF Chambers, Kyle J. Pearse, Allison Coveney, Jonathan Rogers, Sarah Kamani, Dipti Sritharan, Niranjan Randolph, Gregory W. TI Respiratory Variation Predicts Optimal Endotracheal Tube Placement for Intra-operative Nerve Monitoring in Thyroid and Parathyroid Surgery SO WORLD JOURNAL OF SURGERY LA English DT Article ID RECURRENT LARYNGEAL NERVE; PATTERNS; PLAUDITS; PITFALLS; INJURY AB Intra-operative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) during thyroid and parathyroid surgery is thought to aid in identification and dissection of the RLN. While utilization of IONM is increasing, one area of variability in its application is the assessment of adequate endotracheal tube electrode placement for IONM during the case. The main objective of this study is to assess the overall success of utilizing respiratory variation to confirm proper endotracheal tube placement for RLN monitoring. A prospective study of RLN monitoring during thyroid and parathyroid surgery at an academic referral center. Fifty-five cases were included. Fifty (91 %) achieved optimal respiratory variation during endotracheal tube position. Five (9 %) required repeat laryngoscopy to confirm correct endotracheal tube placement following patient positioning. For the respiratory variation group, average amplitude achieved during initial vagus, maximum vagus, initial RLN, and maximal RLN was 700 (+/- 474) mA, 921 (+/- 616) mA, 887 (+/- 584) mA, and 1330 (+/- 843) mA during evoked stimulation, respectively. For the repeat laryngoscopy group, average amplitude achieved during initial vagus, maximum vagus, initial RLN, and maximal RLN evoked stimulation was 591 (+/- 364) mA, 959 (+/- 306) mA, 771 (+/- 424) mA, and 1462 (+/- 855) mA during evoked stimulation, respectively. There was no statistical difference between the two groups for average initial vagus amplitude (p = 0.62), average maximum vagus amplitude (p = 0.89), average initial RLN amplitude (p = 0.67), or average maximum RLN amplitude (p = 0.74). The findings of this study support the International Neural Monitoring Study Group recommendation that confirmation of endotracheal tube electrode placement be performed either by confirmation of adequate respiratory variation or by repeat direct laryngoscopy. C1 [Chambers, Kyle J.; Pearse, Allison; Coveney, Jonathan; Rogers, Sarah; Kamani, Dipti; Sritharan, Niranjan] Harvard Univ, Div Thyroid & Parathyroid Endocrine Surg, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Sch Med, Boston, MA 02138 USA. [Randolph, Gregory W.] Harvard Univ, Sch Med, Dept Surg, Div Surg Oncol,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kamani, D (reprint author), Harvard Univ, Div Thyroid & Parathyroid Endocrine Surg, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Sch Med, Boston, MA 02138 USA. EM dipti_kamani@meei.harvard.edu; Gregory_Randolph@meei.harvard.edu FU John and Claire Bertucci Thyroid Research fund FX This work was funded by the John and Claire Bertucci Thyroid Research fund. NR 23 TC 3 Z9 3 U1 0 U2 2 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 FEB PY 2015 VL 39 IS 2 BP 393 EP 399 DI 10.1007/s00268-014-2820-8 PG 7 WC Surgery SC Surgery GA AZ4XK UT WOS:000348224100016 PM 25297816 ER PT J AU Shamji, MH Bellido, V Scadding, GW Layhadi, JA Cheung, DKM Calderon, MA Asare, A Gao, Z Turka, LA Tchao, N Togias, A Phippard, D Durham, SR AF Shamji, M. H. Bellido, V. Scadding, G. W. Layhadi, J. A. Cheung, D. K. M. Calderon, M. A. Asare, A. Gao, Z. Turka, L. A. Tchao, N. Togias, A. Phippard, D. Durham, S. R. TI Effector cell signature in peripheral blood following nasal allergen challenge in grass pollen allergic individuals SO ALLERGY LA English DT Article DE basophils; IL-4; nasal allergen challenge; seasonal allergic rhinitis; T cells ID DENDRITIC CELLS; INDUCED RHINITIS; MESSENGER-RNA; MUCOSA; PROVOCATION; MEDIATORS; RESPONSES; RELEASE; IMMUNOTHERAPY; EOSINOPHILS AB BackgroundSeveral studies have demonstrated the time course of inflammatory mediators in nasal fluids following nasal allergen challenge (NAC), whereas the effects of NAC on cells in the periphery are unknown. We examined the time course of effector cell markers (for basophils, dendritic cells and T cells) in peripheral blood after nasal grass pollen allergen challenge. MethodsTwelve participants with seasonal allergic rhinitis underwent a control (diluent) challenge followed by NAC after an interval of 14days. Nasal symptoms and peak nasal inspiratory flow (PNIF) were recorded along with peripheral basophil, T-cell and dendritic cell responses (flow cytometry), T-cell proliferative responses (thymidine incorporation), and cytokine expression (FluoroSpot assay). ResultsRobust increases in nasal symptoms and decreases in PNIF were observed during the early (0-1h) response and modest significant changes during the late (1-24h) response. Sequential peaks in peripheral blood basophil activation markers were observed (CD107a at 3h, CD63 at 6h, and CD203c(bright) at 24h). T effector/memory cells (CD4(+)CD25(lo)) were increased at 6h and accompanied by increases in CD80(+) and CD86(+) plasmacytoid dendritic cells (pDCs). Ex vivo grass antigen-driven T-cell proliferative responses and the frequency of IL-4(+)CD4(+) T cells were significantly increased at 6h after NAC when compared to the control day. ConclusionBasophil, T-cell, and dendritic cell activation increased the frequency of allergen-driven IL-4(+)CD4(+) T cells, and T-cell proliferative responses are detectable in the periphery after NAC. These data confirm systemic cellular activation following a local nasal provocation. C1 [Shamji, M. H.; Layhadi, J. A.; Cheung, D. K. M.; Durham, S. R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Immunomodulat & Tolerance Grp, London SW7 2AZ, England. [Bellido, V.; Scadding, G. W.; Layhadi, J. A.; Cheung, D. K. M.; Calderon, M. A.; Durham, S. R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England. [Asare, A.; Gao, Z.; Turka, L. A.; Tchao, N.; Phippard, D.] Immune Tolerance Network, Bethesda, MD USA. [Turka, L. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Togias, A.] NIAID, Bethesda, MD 20892 USA. RP Durham, SR (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst, Sir Alexander Fleming Bldg, London SW7 2AZ, England. EM s.durham@imperial.ac.uk FU Immune Tolerance Network (NIH), an international clinical research consortium headquartered at the University of California San Francisco [N01 AI15416]; National Institute of Allergy and Infectious Diseases; Juvenile Diabetes Research Foundation; Wellcome Trust; Royal Brompton Hospital Charitable Trust Fund FX This research was performed with the support of the Immune Tolerance Network (NIH Contract #N01 AI15416; www.immunetolerance.org), an international clinical research consortium headquartered at the University of California San Francisco and supported by the National Institute of Allergy and Infectious Diseases and the Juvenile Diabetes Research Foundation. Dr Guy Scadding is supported by a Wellcome Trust Clinical Fellowship. This research was also supported by a grant from the Royal Brompton Hospital Charitable Trust Fund. NR 31 TC 7 Z9 8 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD FEB PY 2015 VL 70 IS 2 BP 171 EP 179 DI 10.1111/all.12543 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA AZ0UM UT WOS:000347960300005 PM 25377909 ER PT J AU Liu, KD Yang, W Go, AS Anderson, AH Feldman, HI Fischer, MJ He, J Kallem, RR Kusek, JW Master, SR Miller, ER Rosas, SE Steigerwalt, S Tao, KX Weir, MR Hsu, CY AF Liu, Kathleen D. Yang, Wei Go, Alan S. Anderson, Amanda H. Feldman, Harold I. Fischer, Michael J. He, Jiang Kallem, Radhakrishna R. Kusek, John W. Master, Stephen R. Miller, Edgar R., III Rosas, Sylvia E. Steigerwalt, Susan Tao, Kaixiang Weir, Matthew R. Hsu, Chi-yuan CA CRIC Study Investigators TI Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Neutrophil gelatinase-associated lipocalin (NGAL); renal tubular injury; renal tubular dysfunction; biomarker; chronic kidney disease (CKD); Chronic Renal Insufficiency Cohort (CRIC) Study; cardiovascular disease; ischemic atherosclerotic event ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; INJURY MOLECULE-1 KIM-1; HEART-FAILURE; ATHEROSCLEROSIS RISK; ALL-CAUSE; NGAL; MORTALITY; DAMAGE; BIOMARKERS AB Background: Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria). Study Design: Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study. Setting & Participants: 3,386 participants with estimated glomerular filtration rate of 20 to 70 mL/min/1.73 m(2) enrolled from June 2003 through August 2008. Predictor: Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. Outcomes: Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011. Measurements: Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). Results: There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5 ng/mL] vs lowest [<= 6.9 ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. Limitations: Urine NGAL was measured only once. Conclusions: Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths. (C) 2015 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Liu, Kathleen D.; Hsu, Chi-yuan] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Yang, Wei; Anderson, Amanda H.; Feldman, Harold I.; Kallem, Radhakrishna R.; Tao, Kaixiang] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Go, Alan S.; Hsu, Chi-yuan] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Fischer, Michael J.] Jesse Brown VAMC, Dept Med, Chicago, IL USA. [Fischer, Michael J.] Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA. [He, Jiang] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD USA. [Master, Stephen R.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Miller, Edgar R., III] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA. [Rosas, Sylvia E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Steigerwalt, Susan] St John Hosp & Med Ctr, St Claire Specialty Phys, Detroit, MI USA. [Weir, Matthew R.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. RP Hsu, CY (reprint author), Univ Calif San Francisco, Div Nephrol, 521 Parnassus Ave,C443,Box 0532, San Francisco, CA 94143 USA. EM hsuchi@medicine.ucsf.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902]; Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS) [UL1TR000003]; Johns Hopkins University grant [UL1 TR-000424]; University of Maryland General Clinical Research Center grant [M01 RR-16500]; Clinical and Translational Science Collaborative of Cleveland from the NCATS component of the NIH [UL1TR000439]; NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research grant [UL1TR000433]; University of Illinois at Chicago Clinical and Translational Science Award [UL1RR029879]; Tulane University Translational Research in Hypertension and Renal Biology grant [P30GM103337]; Kaiser Permanente NIH/National Center for Research Resources UCSF-CTSI grant [UL1 RR-024131]; CKD Biomarker Consortium [U01DK85649] FX Funding for the CRIC Study was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by the following: the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS) UL1TR000003, Johns Hopkins University grant UL1 TR-000424, University of Maryland General Clinical Research Center grant M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, grant UL1TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research grant UL1TR000433, University of Illinois at Chicago Clinical and Translational Science Award UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology grant P30GM103337, and Kaiser Permanente NIH/National Center for Research Resources UCSF-CTSI grant UL1 RR-024131. Drs Liu, Go, Feldman, and Hsu also are supported by grant U01DK85649 as members of the CKD Biomarker Consortium. NR 41 TC 12 Z9 14 U1 0 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 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2015 VL 65 IS 2 BP 267 EP 274 DI 10.1053/j.ajkd.2014.07.025 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AZ4MT UT WOS:000348196400013 PM 25311702 ER PT J AU Wang, H Xu, ZP Wu, AS Dong, YL Zhang, YY Yue, Y Xie, ZC AF Wang, Hui Xu, Zhipeng Wu, Anshi Dong, Yuanlin Zhang, Yiying Yue, Yun Xie, Zhongcong TI 2-Deoxy-D-Glucose Enhances Anesthetic Effects in Mice SO ANESTHESIA AND ANALGESIA LA English DT Article ID PROTECTS HIPPOCAMPAL-NEURONS; ISOFLURANE-INDUCED APOPTOSIS; COMPLEX-I FUNCTION; CAENORHABDITIS-ELEGANS; MITOCHONDRIAL-FUNCTION; GENERAL-ANESTHESIA; INDUCED NEUROTOXICITY; VOLATILE-ANESTHETICS; RESPIRATORY-CHAIN; L-CARNITINE AB BACKGROUND: The mechanisms of general anesthesia by volatile drugs remain largely unknown. Mitochondrial dysfunction and reduction in energy levels have been suggested to be associated with general anesthesia status. 2-Deoxy-D-glucose (2-DG), an analog of glucose, inhibits hexokinase and reduces cellular levels of adenosine triphosphate (ATP). 3-Nitropropionic acid is another compound which can deplete ATP levels. In contrast, idebenone and l-carnitine could rescue deficits of energy. We therefore sought to determine whether 2-DG and/or 3-nitropropionic acid can enhance the anesthetic effects of isoflurane, and whether idebenone and l-carnitine can reverse the actions of 2-DG. METHODS: C57BL/6J mice (8 months old) received different concentrations of isoflurane with and without the treatments of 2-DG, 3-nitropropionic acid, idebenone, and l-carnitine. Isoflurane-induced loss of righting reflex (LORR) was determined in the mice. ATP levels in H4 human neuroglioma cells were assessed after these treatments. Finally, 31P-magnetic resonance spectroscopy was used to determine the effects of isoflurane on brain ATP levels in the mice. RESULTS: 2-DG enhanced isoflurane-induced LORR (P = 0.002, N = 15). 3-Nitropropionic acid also enhanced the anesthetic effects of isoflurane (P = 0.005, N = 15). Idebenone (idebenone + saline versus idebenone + 2-DG: P = 0.165, N = 15), but not l-carnitine (l-carnitine + saline versus l-carnitine + 2-DG: P < 0.0001, N = 15), inhibited the effects of 2-DG on enhancing isoflurane-induced LORR in the mice, as evidenced by 2-DG not enhancing isoflurane-induced LORR in the mice pretreated with idebenone. Idebenone (idebenone + saline versus idebenone + 2-DG: P = 0.177, N = 6), but not l-carnitine (l-carnitine + saline versus l-carnitine + 2-DG: P = 0.029, N = 6), also mitigated the effects of 2-DG on reducing ATP levels in cells, as evidenced by 2-DG not decreasing ATP levels in the cells pretreated with idebenone. Finally, isoflurane decreased ATP levels in both cultured cells and mouse brains (beta-ATP: P = 0.003, N = 10; beta-ATP/phosphocreatine: P = 0.006, N = 10; beta-ATP/inorganic phosphate: P = 0.001, N = 10). CONCLUSIONS: These results from our pilot studies have established a system and generated a hypothesis that 2-DG enhances anesthetic effects via reducing energy levels. These findings should promote further studies to investigate anesthesia mechanisms. C1 [Wang, Hui; Wu, Anshi; Yue, Yun] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesia, Beijing, Peoples R China. [Wang, Hui; Xu, Zhipeng; Dong, Yuanlin; Zhang, Yiying; Xie, Zhongcong] Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02129 USA. [Wang, Hui; Xu, Zhipeng; Dong, Yuanlin; Zhang, Yiying; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA USA. [Xu, Zhipeng] Chinese Peoples Liberat Army Gen Hosp, Anesthesia & Operat Ctr, Beijing, Peoples R China. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4310, Boston, MA 02129 USA. EM zxie@mgh.harvard.edu FU National Institutes of Health, Bethesda, MD [R21AG038994, R01 GM088801, R01 AG041274]; Investigator-Initiated Research Grant from Alzheimer's Association, Chicago, IL; Cure Alzheimer's Fund, Wellesley, MA; China National Science Foundation Overseas Young Scholars Collaboration Research Award [NSF30928026] FX This research was supported by R21AG038994, R01 GM088801, and R01 AG041274 from National Institutes of Health, Bethesda, MD, Investigator-Initiated Research Grant from Alzheimer's Association, Chicago, IL, and Cure Alzheimer's Fund, Wellesley, MA (to ZX), and China National Science Foundation Overseas Young Scholars Collaboration Research Award NSF30928026 (to YY and ZX). NR 51 TC 7 Z9 7 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 2015 VL 120 IS 2 BP 312 EP 319 DI 10.1213/ANE.0000000000000520 PG 8 WC Anesthesiology SC Anesthesiology GA AZ3PG UT WOS:000348138700008 PM 25390277 ER PT J AU Hilgendorf, I Swirski, FK Robbins, CS AF Hilgendorf, Ingo Swirski, Filip K. Robbins, Clinton S. TI Monocyte Fate in Atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; cardiovascular disease; inflammation; macrophage; monocyte ID ACUTE MYOCARDIAL-INFARCTION; LOW-DENSITY-LIPOPROTEIN; STEM-CELL PROLIFERATION; HEMATOPOIETIC PROGENITOR CELLS; ACUTE CORONARY SYNDROMES; RECEPTOR KNOCKOUT MICE; ISCHEMIC-HEART FAILURE; CLASS-A OVEREXPRESSION; MARROW-DERIVED CELLS; BONE-MARROW AB Monocytes and their descendant macrophages are essential to the development and exacerbation of atherosclerosis, a lipid-driven inflammatory disease. Lipid-laden macrophages, known as foam cells, reside in early lesions and advanced atheromata. Our understanding of how monocytes accumulate in the growing lesion, differentiate, ingest lipids, and contribute to disease has advanced substantially over the last several years. These cells' remarkable phenotypic and functional complexity is a therapeutic opportunity: in the future, treatment and prevention of cardiovascular disease and its complications may involve specific targeting of atherogenic monocytes/macrophages and their products. C1 [Hilgendorf, Ingo] Univ Freiburg, Ctr Heart, Dept Cardiol & Angiol, D-79106 Freiburg, Germany. [Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Robbins, Clinton S.] Univ Toronto, Toronto Gen Res Inst, Peter Munk Cardiac Ctr, Dept Lab Med, Toronto, ON M5G 1L7, Canada. [Robbins, Clinton S.] Univ Toronto, Toronto Gen Res Inst, Peter Munk Cardiac Ctr, Dept Pathobiol & Immunol, Toronto, ON M5G 1L7, Canada. RP Hilgendorf, I (reprint author), Univ Freiburg, Ctr Heart, Dept Cardiol & Angiol 1, Hugstetter St 55, D-79106 Freiburg, Germany. EM ingo.hilgendorf@universitaets-herzzentrum.de; clint.robbins@utoronto.ca FU DFG (German Research Foundation) [HI 1573/2-1]; Canadian Institutes of Health Research [311523]; Peter Munk Chair in Aortic Disease Research FX This work was supported in part by DFG (German Research Foundation) grant HI 1573/2-1 (to I. Hilgendorf), the Canadian Institutes of Health Research grant 311523 (to C.S. Robbins), and the Peter Munk Chair in Aortic Disease Research (to C.S. Robbins). NR 110 TC 27 Z9 28 U1 3 U2 19 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 FEB PY 2015 VL 35 IS 2 BP 272 EP 279 DI 10.1161/ATVBAHA.114.303565 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AZ4TE UT WOS:000348215100006 PM 25538208 ER PT J AU Abdelbaky, A Corsini, E Figueroa, AL Subramanian, S Fontanez, S Emami, H Hoffmann, U Narula, J Tawakol, A AF Abdelbaky, Amr Corsini, Erin Figueroa, Amparo L. Subramanian, Sharath Fontanez, Sara Emami, Hamed Hoffmann, Udo Narula, Jagat Tawakol, Ahmed TI Early aortic valve inflammation precedes calcification: A longitudinal FDG-PET/CT study SO ATHEROSCLEROSIS LA English DT Article DE Aortic valve calcification; FED-PET; Aortic valve inflammation ID POSITRON-EMISSION-TOMOGRAPHY; CORONARY-ARTERY CALCIUM; DISEASE PROGRESSION; RISK-FACTORS; STENOSIS; ATHEROSCLEROSIS; FLUORODEOXYGLUCOSE; DETERMINANTS; POPULATION; SCLEROSIS AB Objectives: Recent data shows a relationship between aortic valve (AV) inflammation and calcification. However, direct evidence linking early valve inflammation (prior to hemodynamic compromise) to subsequent calcium (Ca) deposition is lacking in humans. We sought to test the hypothesis whether local AV inflammation predisposes to subsequent AV Ca deposition. Methods: We identified 111 individuals (age 60[ 49, 68], 50.5% male) without active cancer or aortic stenosis who underwent 2 PET/CT studies 1-5 years apart for cancer surveillance. AV inflammation was determined by measuring FDG uptake (maximum standardized uptake value, SUVmax) within the AV on baseline PET/CT. Subsequent deposition of AV Ca was determined by comparing baseline and follow-up CT scans, determined as an increase in AV Ca volume score (CaVS). Patients were classified as "non-progressors" or "progressors" based on Square Root difference in CaVS (using a pre-determined cut-off value of 2.5). CT and PET measurements were conducted by 2 mutually blinded laboratories. Results: During follow-up, AV Ca increased in 23 patients (20.2%) classified as "progressors", of whom 9 (9.2%) demonstrated subsequent 'incident' AV Ca. The AV SUVmax (mean +/- SD) was higher in progressors vs. non-progressors (2.03 +/- 0.52 vs. 1.74 +/- 0.36, p = 0.02) and especially in patients with-vs. without-incident AV Ca (2.28 +/- 0.42 vs. 1.73 +/- 0.36, p < 0.001). Moreover, AV inflammation (AV SUVmax) independently predicted subsequent calcification after adjusting for cardiovascular risk factors [OR (95%CI): 4.99 (1.30-19.15), p = 0.02]. Conclusion: The findings suggest that early AV inflammation may predispose to AV sclerosis. The evaluation of valvular metabolic activity may prove useful for developing a better understanding of calcific valve disease. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Abdelbaky, Amr; Corsini, Erin; Figueroa, Amparo L.; Subramanian, Sharath; Fontanez, Sara; Emami, Hamed; Hoffmann, Udo; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Narula, Jagat] Mt Sinai Sch Med, Div Cardiol, New York, NY USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@mgh.harvard.edu OI Corsini, Erin/0000-0003-4715-0244 NR 36 TC 10 Z9 10 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2015 VL 238 IS 2 BP 165 EP 172 DI 10.1016/j.atherosclerosis.2014.11.026 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AZ1UL UT WOS:000348023000003 PM 25525744 ER PT J AU Shahian, DM Normand, SLT AF Shahian, David M. Normand, Sharon-Lise T. TI What is a performance outlier? SO BMJ QUALITY & SAFETY LA English DT Editorial Material ID PROFILING HOSPITAL PERFORMANCE; 30-DAY MORTALITY-RATES; QUALITY-OF-CARE; RISK-ADJUSTMENT; SURGICAL QUALITY; CARDIAC-SURGERY; INSTITUTIONAL PERFORMANCE; BYPASS-SURGERY; FUNNEL PLOTS; OUTCOMES C1 [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Ctr Qual & Safety, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 47 TC 9 Z9 9 U1 1 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD FEB PY 2015 VL 24 IS 2 BP 95 EP 99 DI 10.1136/bmjqs-2015-003934 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AZ4PC UT WOS:000348203800003 PM 25605952 ER PT J AU Singh, H Sittig, DF AF Singh, Hardeep Sittig, Dean F. TI Advancing the science of measurement of diagnostic errors in healthcare: the Safer Dx framework SO BMJ QUALITY & SAFETY LA English DT Article ID ADVERSE EVENTS; MALPRACTICE CLAIMS; PATIENT SAFETY; HOSPITALIZED-PATIENTS; AMBULATORY-CARE; MEDICAL-RECORD; ORGANIZATIONS; SURVEILLANCE; SETTINGS; IMPROVE AB Diagnostic errors are major contributors to harmful patient outcomes, yet they remain a relatively understudied and unmeasured area of patient safety. Although they are estimated to affect about 12 million Americans each year in ambulatory care settings alone, both the conceptual and pragmatic scientific foundation for their measurement is under-developed. Health care organizations do not have the tools and strategies to measure diagnostic safety and most have not integrated diagnostic error into their existing patient safety programs. Further progress toward reducing diagnostic errors will hinge on our ability to overcome measurement-related challenges. In order to lay a robust groundwork for measurement and monitoring techniques to ensure diagnostic safety, we recently developed a multifaceted framework to advance the science of measuring diagnostic errors (The Safer Dx framework). In this paper, we describe how the framework serves as a conceptual foundation for system-wide safety measurement, monitoring and improvement of diagnostic error. The framework accounts for the complex adaptive sociotechnical system in which diagnosis takes place (the structure), the distributed process dimensions in which diagnoses evolve beyond the doctor's visit (the process) and the outcomes of a correct and timely "safe diagnosis" as well as patient and health care outcomes (the outcomes). We posit that the Safer Dx framework can be used by a variety of stakeholders including researchers, clinicians, health care organizations and policymakers, to stimulate both retrospective and more proactive measurement of diagnostic errors. The feedback and learning that would result will help develop subsequent interventions that lead to safer diagnosis, improved value of health care delivery and improved patient outcomes. C1 [Singh, Hardeep] Michael E DeBakey VA Med Ctr, Houston Vet Affairs Ctr Innovat Qual Effectivenes, Houston, TX USA. [Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Sittig, Dean F.] Univ Texas Sch Biomed Informat, Houston, TX USA. [Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. RP Singh, H (reprint author), VA Med Ctr 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu FU VA Health Services Research and Development Service [CRE 12-033]; VA National Center for Patient Safety; Agency for Health Care Research and Quality [R01HS022087]; Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX HS is supported by the VA Health Services Research and Development Service (CRE 12-033; Presidential Early Career Award for Scientists and Engineers USA 14-274), the VA National Center for Patient Safety and the Agency for Health Care Research and Quality (R01HS022087). This work is supported in part by the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). HS presented the Safer Dx framework to the Institute of Medicine Diagnostic Error in Health Care Consensus Study Committee on 6 August 2014. NR 59 TC 17 Z9 17 U1 2 U2 12 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD FEB PY 2015 VL 24 IS 2 BP 103 EP 110 DI 10.1136/bmjqs-2014-003675 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AZ4PC UT WOS:000348203800005 PM 25589094 ER PT J AU Turan, S Thiele, S Tafaj, O Brix, B Atay, Z Abali, S Haliloglu, B Bereket, A Bastepe, M AF Turan, Serap Thiele, Susanne Tafaj, Olta Brix, Bettina Atay, Zeynep Abali, Saygin Haliloglu, Belma Bereket, Abdullah Bastepe, Murat TI Evidence of hormone resistance in a pseudo-pseudohypoparathyroidism patient with a novel paternal mutation in GNAS SO BONE LA English DT Article DE Pseudohypoparathyroidism; Pseudopseudohypoparathyroidism; GNAS; Hormone resistance ID ALBRIGHT HEREDITARY OSTEODYSTROPHY; XL-ALPHA-S; MATERNAL TRANSMISSION; GROWTH-HORMONE; GS-ALPHA; GENE; PSEUDOPSEUDOHYPOPARATHYROIDISM; DEFICIENCY; G(S)ALPHA; LOCUS AB Context: Loss-of-function GNAS mutations lead to hormone resistance and Albright's hereditary osteodystrophy (AHO) when maternally inherited, i.e. pseudohypoparathyroidism-Ia (PHPIa), but cause AHO alone when located on the paternal allele, i.e. pseudoPHP (PPHP). Objective: We aimed to establish the molecular diagnosis in a patient with AHO and evidence of hormone resistance. Case: The patient is a female who presented at the age of 13.5 years with short stature and multiple AHO features. No evidence for TSH or gonadotropin-resistance was present. Serum calcium and vitamin D levels were normal. However, serum PTH was elevated on multiple occasions (64-178 pg/mL, normal: 9-52) and growth hormone response to clonidine or L-DOPA was blunted, suggesting hormone resistance and PHP-Ia. The patient had diminished erythrocyte Gm activity and a novel heterozygous GNAS mutation (c.328 G>C; p.A109P). The mother lacked the mutation, and the father's DNA was not available. Hence, a diagnosis of PPHP also appeared possible, supported by low birth weight and a lack of AHO features associated predominantly with PHP-Ia, i.e. obesity and cognitive impairment. To determine the parental origin of the mutation, we amplified the paternally expressed A/B and biallelically expressed Gs alpha transcripts from the patient's peripheral blood RNA. While both wild-type and mutant nucleotides were detected in the Gs alpha amplicon, only the mutant nucleotide was present in the A/B amplicon, indicating that the mutation was paternal. Conclusion: These findings suggest that PTH and other hormone resistance may not be an exclusive feature of PHP-Ia and could also be observed in patients with PPHP. (C) 2014 Elsevier Inc. All rights reserved. C1 [Turan, Serap; Atay, Zeynep; Abali, Saygin; Haliloglu, Belma; Bereket, Abdullah] Marmara Univ, Dept Pediat Endocrinol, Istanbul, Turkey. [Thiele, Susanne; Brix, Bettina] Med Univ Lubeck, Div Expt Paediat Endocrinol & Diabet, Lubeck, Germany. [Tafaj, Olta; Bastepe, Murat] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 55 Fruit St Thier 10, Boston, MA 02114 USA. EM serap.turan@marmara.edu.tr; bastepe@helix.mgh.harvard.edu FU NIH/NIDDK [RO1DK073911]; University of Luebeck [E48-2013] FX Molecular genetic studies were funded in part by the NIH/NIDDK grant to M.B. (RO1DK073911) and a grant of the University of Luebeck to S.T.2 (E48-2013). NR 29 TC 6 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 8756-3282 EI 1873-2763 J9 BONE JI Bone PD FEB PY 2015 VL 71 BP 53 EP 57 DI 10.1016/j.bone.2014.10.006 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AY7XU UT WOS:000347770000007 PM 25464124 ER PT J AU Wasfy, MM DeLuca, J Wang, F Berkstresser, B Ackerman, KE Eisman, A Lewis, GD Hutter, AM Weiner, RB Baggish, AL AF Wasfy, Meagan M. DeLuca, James Wang, Francis Berkstresser, Brant Ackerman, Kathryn E. Eisman, Aaron Lewis, Gregory D. Hutter, Adolph M. Weiner, Rory B. Baggish, Aaron L. TI ECG findings in competitive rowers: normative data and the prevalence of abnormalities using contemporary screening recommendations SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Article ID EARLY REPOLARIZATION PATTERN; SUDDEN CARDIAC DEATH; T-WAVE; CLINICAL-SIGNIFICANCE; CONSENSUS STATEMENT; EUROPEAN-SOCIETY; SEATTLE CRITERIA; OF-CARDIOLOGY; UNITED-STATES; ENDURANCE AB Background/aim The international governing body for competitive rowing recently mandated the inclusion of 12-lead ECG during preparticipation screening. We therefore sought to describe normative ECG characteristics and to examine the prevalence of abnormal ECG findings as defined by contemporary athlete ECG interpretation criteria among competitive rowers. Methods Competitive rowers (n=330, 56% male) underwent standard 12-lead ECG at the time of collegiate preparticipation screening. ECGs were analysed quantitatively to develop a sport-specific normative database and then for the presence of abnormalities in accordance with the 2010 European Society of Cardiology (ESC) recommendations and 2013 'Seattle Criteria.' Results 94% of rowers had one or more training-related ECG patterns including sinus bradycardia (51%), sinus arrhythmia (55%), and incomplete right bundle branch block (42%). Males were more likely than females to have isolated voltage criteria for left ventricular hypertrophy (LVH) (51% vs 8%, p<0.001) and early repolarisation pattern (76% vs 23%, p<0.001). Application of the 2010 ESC criteria, compared to the Seattle criteria, resulted in the classification of a significantly greater number of abnormal ECGs (47% vs 4%; p<0.001). The detection of true pathology, accomplished by both interpretation criteria, was confined to a single case of ventricular pre-excitation. Conclusions Training-related ECG patterns with several gender-based differences are common among competitive rowers. The diagnostic accuracy and downstream clinical implications of ECG-inclusive preparticipation screening among rowers will be dictated by the choice and future refinement of ECG interpretation criteria. C1 [Wasfy, Meagan M.; DeLuca, James; Eisman, Aaron; Lewis, Gregory D.; Hutter, Adolph M.; Weiner, Rory B.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. [Wang, Francis; Berkstresser, Brant; Baggish, Aaron L.] Harvard Univ Hlth Serv, Cambridge, MA USA. [Ackerman, Kathryn E.] Boston Childrens Hosp, Div Sports Med, Boston, MA USA. [Ackerman, Kathryn E.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, 55 Fruit St,Yawkey Suite 5B, Boston, MA 02114 USA. EM abaggish@partners.org FU American Heart Association [FTF2220328] FX The authors wish to thank Harvard crew coaches Charlie Butt, Linda Muri, William Manning, and Billy Boyce and for their on-going partnership. The authors acknowledge the late Harry Parker for his steadfast support of the Harvard Athlete Initiative and his firm belief in the value of sport science. The authors wish to thank Ms. Deborah McDonald for clerical oversight. This study was funded, in part by a research grant from the American Heart Association FTF2220328 (ALB). NR 34 TC 11 Z9 11 U1 1 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 EI 1473-0480 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD FEB PY 2015 VL 49 IS 3 BP 200 EP 206 DI 10.1136/bjsports-2014-093919 PG 7 WC Sport Sciences SC Sport Sciences GA AZ2OY UT WOS:000348073800014 PM 25202138 ER PT J AU Coutinho, JF Goncalves, OF Maia, L Vasconcelos, CF Perrone-McGovern, K Simon-Dack, S Hernandez, K Oliveira-Silva, P Mesquita, AR Sampaio, A AF Coutinho, Joana Fernandes Goncalves, Oscar Filipe Maia, Liliana Vasconcelos, Cristiana Fernandes Perrone-McGovern, Kristin Simon-Dack, Stephanie Hernandez, Kristina Oliveira-Silva, Patricia Mesquita, Ana Raquel Sampaio, Adriana TI Differential activation of the default mode network in jet lagged individuals SO CHRONOBIOLOGY INTERNATIONAL LA English DT Article DE Brain; default mode network; jet lag ID ANTERIOR CINGULATE CORTEX; FUNCTIONAL CONNECTIVITY; COGNITIVE DEFICITS; COPING STRATEGIES; CORTISOL-LEVELS; SOCIAL PHOBIA; BRAIN; PERFORMANCE; MEMORY; SHIFT AB Long-term exposure to transmeridian flights has been shown to impact cognitive functioning. Nevertheless, the immediate effects of jet lag in the activation of specific brain networks have not been investigated. We analyzed the impact of short-term jet lag on the activation of the default mode network (DMN). A group of individuals who were on a transmeridian flight and a control group went through a functional magnetic resonance imaging acquisition. Statistical analysis was performed to test for differences in the DMN activation between groups. Participants from the jet lag group presented decreased activation in the anterior nodes of the DMN, specifically in bilateral medial prefrontal and anterior cingulate cortex. No areas of increased activation were observed for the jet lag group. These results may be suggestive of a negative impact of jet lag on important cognitive functions such as introspection, emotional regulation and decision making in a few days after individuals arrive at their destination. C1 [Coutinho, Joana Fernandes; Goncalves, Oscar Filipe; Maia, Liliana; Oliveira-Silva, Patricia; Mesquita, Ana Raquel; Sampaio, Adriana] Univ Minho, Sch Psychol, CIPsi, Neuropsychophysiol Lab, P-4710057 Braga, Portugal. [Goncalves, Oscar Filipe] Northeastern Univ, Bouve Coll Hlth Sci, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Goncalves, Oscar Filipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Spaulding Ctr Neuromodulat, Boston, MA USA. [Goncalves, Oscar Filipe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Vasconcelos, Cristiana Fernandes] Hosp Sto Antonio, CHP, Dept Neuroradiol, Oporto, Portugal. [Perrone-McGovern, Kristin] Ball State Univ, Dept Counseling Psychol & Guidance Serv, Muncie, DE USA. [Simon-Dack, Stephanie; Hernandez, Kristina] Ball State Univ, Dept Psychol Sci, Muncie, DE USA. RP Coutinho, JF (reprint author), Univ Minho, Sch Psychol, Campus Gualtar, P-4710057 Braga, Portugal. EM joanafpc@gmail.com RI Goncalves, Oscar/G-5278-2010; Perrone-McGovern, Kristin/J-9558-2012; Sampaio, Adriana/C-8361-2011; OI Goncalves, Oscar/0000-0003-2735-9155; Perrone-McGovern, Kristin/0000-0003-0506-1892; Sampaio, Adriana/0000-0001-7347-1282; Coutinho, Joana/0000-0002-1562-0099; Mesquita, Ana/0000-0002-9635-2355 FU Portuguese Foundation for Science and Technology (FCT) - FEDER (POFC - COMPETE) [PIC/IC/83290/2007]; FCT [SFRH/BPD/75014/2010]; Bial Foundation [87/12]; Competitive Factors Operational Programme COMPETE - Portuguese Foundation for Science and Technology [PTDC/PSI-PCL/115316/2009] FX This study was funded by the Portuguese Foundation for Science and Technology (FCT): PIC/IC/83290/2007, which is supported by FEDER (POFC - COMPETE). Joana Coutinho was funded by a FCT postdoctoral grant (number: SFRH/BPD/75014/2010) and Bial Foundation (grant number 87/12). Liliana Maia is supported by the Competitive Factors Operational Programme COMPETE - by national funds from the Portuguese Foundation for Science and Technology (grant PTDC/PSI-PCL/115316/2009). NR 43 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0742-0528 EI 1525-6073 J9 CHRONOBIOL INT JI Chronobiol. Int. PD FEB PY 2015 VL 32 IS 1 BP 143 EP 149 DI 10.3109/07420528.2014.955187 PG 7 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA AZ6AI UT WOS:000348299800015 PM 25180985 ER PT J AU Bernson-Leung, M Ananth, P Shusterman, S AF Bernson-Leung, Miya Ananth, Prasanna Shusterman, Suzanne TI Neuroblastoma Presenting as Facial Nerve Palsy and Bulging Tympanic Membrane SO CLINICAL PEDIATRICS LA English DT Article ID METASTATIC NEUROBLASTOMA; PARALYSIS; CHILDREN C1 [Bernson-Leung, Miya; Ananth, Prasanna; Shusterman, Suzanne] Boston Childrens Hosp, Boston, MA 02215 USA. [Ananth, Prasanna; Shusterman, Suzanne] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bernson-Leung, M (reprint author), Boston Childrens Hosp, Dept Neurol, 300 Longwood Ave,Fegan 11, Boston, MA 02215 USA. EM miya.bernson-leung@childrens.harvard.edu OI Bernson-Leung, Miya/0000-0002-7766-2323 NR 10 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 EI 1938-2707 J9 CLIN PEDIATR JI Clin. Pediatr. PD FEB PY 2015 VL 54 IS 2 BP 183 EP 185 DI 10.1177/0009922814534314 PG 3 WC Pediatrics SC Pediatrics GA AZ4NA UT WOS:000348197200012 PM 24817076 ER PT J AU Singh, A Lester, C Drapp, R Hu, DZ Glimcher, LH Jones, D AF Singh, Anju Lester, Chantel Drapp, Rebecca Hu, Dorothy Z. Glimcher, Laurie H. Jones, Dallas TI Tetraspanin CD9 and ectonucleotidase CD73 identify an osteochondroprogenitor population with elevated osteogenic properties SO DEVELOPMENT LA English DT Article DE Osteochondroprogenitor; Osteoblast; Skeletal stem cell ID MESENCHYMAL STEM-CELLS; PROGENITOR CELLS; REGENERATION; BONES AB Cell-based bone regeneration strategies offer promise for traumatic bone injuries, congenital defects, non-union fractures and other skeletal pathologies. Postnatal bone remodeling and fracture healing provide evidence that an osteochondroprogenitor cell is present in adult life that can differentiate to remodel or repair the fractured bone. However, cell-based skeletal repair in the clinic is still in its infancy, mostly due to poor characterization of progenitor cells and lack of knowledge about their in vivo behavior. Here, we took acombined approachof high-throughput screening, flow-based cell sorting and in vivo transplantation to isolate markers that identify osteochondroprogenitor cells. We show that the presence of tetraspanin CD9 enriches for osteochondroprogenitors within CD105(+) mesenchymal cells and that these cells readily form bone upon transplantation. In addition, we have used Thy1.2 and the ectonucleotidase CD73 to identify subsets within the CD9(+) population that lead to endochondral or intramembranous-like bone formation. Utilization of this unique cell surface phenotype to enrich for osteochondroprogenitor cells will allow for further characterization of the molecular mechanisms that regulate their osteogenic properties. C1 [Singh, Anju] NIH, Dept Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Lester, Chantel] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Drapp, Rebecca] N Carolina State Univ, Coll Vet Med, Raleigh, NC 27607 USA. [Hu, Dorothy Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Glimcher, Laurie H.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [Jones, Dallas] Abide Therapeut, San Diego, CA 92121 USA. RP Singh, A (reprint author), NIH, Dept Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. EM anju.singh@nih.gov; lglimche@med.cornell.edu FU National Institutes of Health [HD055601, K99AR055668]; Arthritis Foundation FX This work was supported by National Institutes of Health grants [HD055601 to L.H.G. and K99AR055668 to D.J.]. A.S. was supported by a fellowship from the Arthritis Foundation. Deposited in PMC for release after 12 months. NR 20 TC 1 Z9 1 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD FEB 1 PY 2015 VL 142 IS 3 BP 438 EP 443 DI 10.1242/dev.113571 PG 6 WC Developmental Biology SC Developmental Biology GA AZ5HT UT WOS:000348251800005 PM 25564652 ER PT J AU Gillern, SM Mahmoud, NN Paulson, EC AF Gillern, Suzanne M. Mahmoud, Najjia N. Paulson, E. Carter TI Local Excision for Early Stage Rectal Cancer in Patients Over Age 65 Years: 2000-2009 SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Local excision; Patterns of care; Rectal cancer; Survey of Epidemiology and End Results-Medicare ID LYMPH-NODE METASTASIS; TRANSANAL ENDOSCOPIC MICROSURGERY; LONG-TERM SURVIVAL; COLORECTAL-CANCER; RADICAL SURGERY; T1; CARCINOMA; THERAPY; RISK; ADENOCARCINOMA AB BACKGROUND: Local excision of rectal cancer is an attractive option because it avoids the morbidity of radical resection. Concerns have arisen during the past decade, however, regarding substandard oncologic results. OBJECTIVE: Using the most recent Survey of Epidemiology and End Results-Medicare data, we examined the change in the use of local excision for rectal cancer from 2000 to 2009 and examined patient, surgeon, and hospital factors related to its use. DESIGN: This study is a retrospective cohort study. SETTINGS: This study was conducted at a tertiary care medical center using Survey of Epidemiology and End Results-Medicare data. PATIENTS: Patients with pathologic Tis, T1, or T2 rectal cancer who were >65 years of age and underwent primary radical resection or local excision between 2000 and 2009 were included in this study. MAIN OUTCOME MEASURES: The change in the use of local excision for rectal cancer from 2000 to 2009 was the main outcome measured. RESULTS: A total of 8966 patients were identified. The use of local excision decreased significantly between 2000 and 2009. Women and patients who were older and had more comorbidities were significantly more likely to undergo local excision. Having a colorectal surgeon perform the surgery increased the odds of local excision by 1.5 times (p < 0.001). Similar trends were seen in patients operated on at the National Cancer Institute (OR, 1.7; p < 0.001) and teaching hospitals (OR, 1.2; p = 0.003). Younger surgeons were more likely to perform local excisions. For surgeons graduating in 1980-1989 or 1990 and after, the odds of local excision were 1.40 (p = 0.001) and 2.1 (p < 0.001) compared with surgeons graduating before 1970. LIMITATIONS: The study was limited by the retrospective design, and the data were collected by multiple healthcare officials in their representative institutions. CONCLUSIONS: In patient >65 years of age, the odds of undergoing local excision for early stage rectal cancer decreased significantly between 2000 and 2009, coincident with evidence of oncologic inferiority. However, there was still significant variation in its use. More studies are needed to better understand these variations in an attempt to bring more uniformity to the use of local excision in early stage rectal cancer. C1 [Gillern, Suzanne M.; Mahmoud, Najjia N.; Paulson, E. Carter] Hosp Univ Penn, Dept Gen Surg, Div Colon & Rectal Surg, Philadelphia, PA 19104 USA. [Paulson, E. Carter] Philadelphia VA Med Ctr, Dept Gen Surg, Philadelphia, PA USA. RP Paulson, EC (reprint author), Surg Business Off, 3900 Woodland Ave,PVAMC 5th Floor, Philadelphia, PA 19104 USA. EM paulsone@uphs.upenn.edu FU Thomas B. and Jeannette E. Laws McCabe Fund FX Funding for this research was provided by the Thomas B. and Jeannette E. Laws McCabe Fund. NR 33 TC 3 Z9 4 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD FEB PY 2015 VL 58 IS 2 BP 172 EP 178 DI 10.1097/DCR.0000000000000279 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AZ4IZ UT WOS:000348186000008 PM 25585074 ER PT J AU Leonard, MM Serena, G Sturgeon, C Fasano, A AF Leonard, Maureen M. Serena, Gloria Sturgeon, Craig Fasano, Alessio TI Genetics and celiac disease: the importance of screening SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE celiac disease; genetic risk; HLA; screening ID INTESTINAL BARRIER FUNCTION; PEDIATRIC-GASTROENTEROLOGY; TISSUE TRANSGLUTAMINASE; INCREASED PREVALENCE; MULTIPLE COMMON; RISK VARIANTS; AT-RISK; HLA; ASSOCIATION; DIAGNOSIS AB The prevalence of celiac disease (CD) is increasing. Despite an increased awareness and an improvement in diagnostic testing, the majority of individuals with CD remain undiagnosed. Currently, genetic testing in screening for CD is used only to exclude a diagnosis or reinforce a strong clinical suspicion. In this paper, we review the most current literature regarding genetic testing in CD. In response to important data revealing that an individual's HLA haplotype is one of the strongest known predictors of CD, we propose genetic screening for at-risk infants to stratify individuals based on genetic risk to ultimately create genetic specific screening algorithms. C1 [Leonard, Maureen M.; Serena, Gloria; Sturgeon, Craig; Fasano, Alessio] Massachusetts Gen Hosp, Ctr Celiac Res, Mucosal Immunol & Biol Res Ctr, Boston, MA 02111 USA. [Leonard, Maureen M.; Serena, Gloria; Sturgeon, Craig; Fasano, Alessio] Massachusetts Gen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA 02111 USA. [Serena, Gloria; Sturgeon, Craig] Univ Maryland, Sch Med, Grad Program Life Sci, Baltimore, MD 21201 USA. RP Leonard, MM (reprint author), Massachusetts Gen Hosp, Ctr Celiac Res, Mucosal Immunol & Biol Res Ctr, 165 Cambridge St, Boston, MA 02111 USA. EM Mleonard7@mgh.harvard.edu NR 68 TC 3 Z9 3 U1 3 U2 26 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1747-4124 EI 1747-4132 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD FEB PY 2015 VL 9 IS 2 BP 209 EP 215 DI 10.1586/17474124.2014.945915 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ1ZZ UT WOS:000348035400010 PM 25294637 ER PT J AU Pins, A Mihm, MC Hoang, MP AF Pins, Adrian Mihm, Martin C., Jr. Hoang, Mai P. TI BAP1 and BRAFV600E expression in benign and malignant melanocytic proliferations SO HUMAN PATHOLOGY LA English DT Article DE BAP1; BRAFV600E; Immunohistochemistry; Nevi; Melanoma ID SPITZ TUMORS; GERMLINE MUTATIONS; BRAF MUTATION; MELANOMA; UVEAL; NEVI; PREDISPOSE; DIAGNOSIS; BRCA1 AB BAPI (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma, and other tumors. Screening for BAPI mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and nondesmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy) and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP] germline mutation. Most sporadic melanocytic lesions exhibited positive BAP1 nuclear staining, except for 1 proliferative nodule arising in congenital nevus, 1 desmoplastic, 1 nevoid, and 2 metastatic melanomas. BRAFV600E positivity was demonstrated in 80% of dermal, 5% of congenital, 6% of Spitz, and 5.5% of atypical Spitz nevi; 29% of proliferative nodules arising in congenital nevi; and 24% of primary and nondesmoplastic and 35% of metastatic melanomas. Combined BAP1 loss and BRAFV600E staining was seen in 67% of BAP1 tumor syndrome-associated lesions and in none of the sporadic melanocytic proliferations including Spitz and atypical Spitz nevi and atypical Spitz tumors, with the exception of 1 primary melanoma. The combined BAP1-BRAFV600E+ immunoprofile appears to be a constant feature of BAP1 tumor syndrome associated melanocytic lesions, and the designation of Spitz nevi or variants thereof appears to be inaccurate for this group of lesions. (C) 2015 Elsevier Inc. All rights reserved. C1 [Pins, Adrian; Mihm, Martin C., Jr.; Hoang, Mai P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pins, Adrian; Mihm, Martin C., Jr.] Massachusetts Gen Hosp, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02114 USA. [Pins, Adrian; Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@mgh.harvard.edu NR 24 TC 0 Z9 0 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2015 VL 46 IS 2 BP 239 EP 245 DI 10.1016/j.humpath.2014.10.015 PG 7 WC Pathology SC Pathology GA AZ5QI UT WOS:000348274600010 ER PT J AU Geyer, JT Subramaniyam, S Jiang, YW Elemento, O Ferry, JA de Leval, L Nakashima, MO Liu, YC Martin, P Mathew, S Orazi, A Tam, W AF Geyer, Julia Turbiner Subramaniyam, Shivakumar Jiang, Yanwen Elemento, Olivier Ferry, Judith A. de Leval, Laurence Nakashima, Megan O. Liu, Yen-Chun Martin, Peter Mathew, Susan Orazi, Attilio Tam, Wayne TI Lymphoblastic transformation of follicular lymphoma: a clinicopathologic and molecular analysis of 7 patients SO HUMAN PATHOLOGY LA English DT Article DE Follicular lymphoma; Lymphoblastic transformation; MYC rearrangement; Double hit lymphoma; TdT staining ID B-CELL LYMPHOMA; MYC GENE REARRANGEMENT; PLASMABLASTIC LYMPHOMA; POOR-PROGNOSIS; TRANSLOCATION; LEUKEMIA; NEOPLASMS; FEATURES; TRANSDIFFERENTIATION; GENERATION AB Approximately 30% of patients with follicular lymphoma (FL) transform to a more aggressive malignancy, most commonly diffuse large B cell lymphoma. Rarely, FL transformation results in clinical findings, histology, and immunophenotype reminiscent of B-Iymphoblastic leukemia/lymphoma. We report the largest series to date with detailed analysis of 7 such patients. Lymphoblastic transformation occurred on average 2 years after initial diagnosis of FL. Five patients had prior intensive chemotherapy. Two patients developed mature high-grade lymphoma, followed by the lymphoblastic transformation. FL had BCL2 gene rearrangement in 4 of 5 cases. High-grade transformation was accompanied by MYC gene rearrangement (5 of 5). Transformation was characterized by expression of TdT, loss of Bcl6, variable loss of immunoglobulin light chain, and persistence of Pax-5, Bcl2, and CD10. Whole-exome sequencing in 1 case revealed presence of several actionable mutations (CD79B, CCND3, CDK12). FL, aggressive mature B cell lymphoma, and lymphoblastic transformation were clonally related in 6 evaluable cases. After transformation, survival ranged from 1 to 14 months. Four patients died of disease, 2 were in remission after stem cell transplant, and 1 was alive with disease. (C) 2015 Elsevier Inc. All rights reserved. C1 [Geyer, Julia Turbiner; Subramaniyam, Shivakumar; Liu, Yen-Chun; Mathew, Susan; Orazi, Attilio; Tam, Wayne] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Jiang, Yanwen; Elemento, Olivier] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10065 USA. [Jiang, Yanwen; Martin, Peter] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [Ferry, Judith A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [de Leval, Laurence] Inst Univ Pathol, CH-1011 Lausanne, Switzerland. [Nakashima, Megan O.] Cleveland Clin, Dept Pathol & Lab Med, Cleveland, OH 44195 USA. RP Geyer, JT (reprint author), New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Pathol & Lab Med, 525 East 68th St, New York, NY 10065 USA. EM jut9021@med.cornll.edu NR 37 TC 7 Z9 7 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 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2015 VL 46 IS 2 BP 260 EP 271 DI 10.1016/j.humpath.2014.10.021 PG 12 WC Pathology SC Pathology GA AZ5QI UT WOS:000348274600013 PM 25529125 ER PT J AU Arku, RE Adamkiewicz, G Vallarino, J Spengler, JD Levy, DE AF Arku, R. E. Adamkiewicz, G. Vallarino, J. Spengler, J. D. Levy, D. E. TI Seasonal variability in environmental tobacco smoke exposure in public housing developments SO INDOOR AIR LA English DT Article DE Indoor air pollution; Second-hand smoke; Particulate matter; Airborne nicotine; Seasonal patterns; Multiunit housing ID SECONDHAND SMOKE; UNITED-STATES; INDOOR; PENETRATION; NONSMOKERS; CHILDREN; MONITOR; OUTDOOR; FINE; RISK AB The risk of tobacco smoking and second-hand smoke (SHS) exposure combined are the leading contributors to disease burden in high-income countries. Recent studies and policies are focusing on reducing exposure to SHS in multiunit housing (MUH), especially public housing. We examined seasonal patterns of SHS levels within indoor common areas located on Boston Housing Authority (BHA) properties. We measured weekly integrated and continuous fine particulate matter (PM2.5) and passive airborne nicotine in six buildings of varying building and occupant characteristics in summer 2012 and winter 2013. The average weekly indoor PM2.5 concentration across all six developments was 9.2g/m(3), higher during winter monitoring period (10.3g/m(3)) compared with summer (8.0g/m(3)). Airborne nicotine concentrations ranged from no detection to about 5000ng/m(3) (mean 311ng/m(3)). Nicotine levels were significantly higher in the winter compared with summer (620 vs. 85ng/m(3); 95% CI: 72-998). Smoking-related exposures within Boston public housing vary by season, building types, and resident smoking policy. Our results represent exposure disparities that may contribute to health disparities in low-income communities and highlight the potential importance of efforts to mitigate SHS exposures during winter when outdoor-indoor exchange rates are low and smokers may tend to stay indoors. Our findings support the use of smoke-free policy as an effective tool to eliminate SHS exposure and protect non-smokers, especially residents of MUH. C1 [Arku, R. E.; Adamkiewicz, G.; Vallarino, J.; Spengler, J. D.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Levy, D. E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Levy, D. E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Adamkiewicz, G (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr, Room 404K WEST,401 Pk Dr, Boston, MA 02215 USA. EM gadamkie@hsph.harvard.edu FU Flight Attendants Medical Research Institute; Harvard School of Public Health; National Cancer Institute's Lung Cancer Disparities Center grant [P50CA148596] FX This work was conducted with support from the Flight Attendants Medical Research Institute, the Harvard School of Public Health, and the National Cancer Institute's Lung Cancer Disparities Center grant #P50CA148596. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. We thank Charles Perrino at the University of California, Berkeley, for preparing and analyzing all passive nicotine monitors. NR 34 TC 10 Z9 10 U1 0 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-6947 EI 1600-0668 J9 INDOOR AIR JI Indoor Air PD FEB PY 2015 VL 25 IS 1 BP 13 EP 20 DI 10.1111/ina.12121 PG 8 WC Construction & Building Technology; Engineering, Environmental; Public, Environmental & Occupational Health SC Construction & Building Technology; Engineering; Public, Environmental & Occupational Health GA AZ3GM UT WOS:000348115500003 PM 24750252 ER PT J AU Herrera, BS Hasturk, H Kantarci, A Freire, MO Nguyen, O Kansal, S Van Dyke, TE AF Herrera, Bruno S. Hasturk, Hatice Kantarci, Alpdogan Freire, Marcelo O. Nguyen, Olivia Kansal, Shevali Van Dyke, Thomas E. TI Impact of Resolvin E1 on Murine Neutrophil Phagocytosis in Type 2 Diabetes SO INFECTION AND IMMUNITY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; HEMOGLOBIN A(1C) LEVELS; PORPHYROMONAS-GINGIVALIS; LIPID MEDIATORS; ANTIINFLAMMATORY ACTIONS; MACROPHAGE INFILTRATION; VASCULAR INFLAMMATION; PERIODONTAL-DISEASE; INSULIN-RESISTANCE; INDUCED COLITIS AB Diabetic complications involve inflammation-mediated microvascular and macrovascular damage, disruption of lipid metabolism, glycosylation of proteins, and abnormalities of neutrophil-mediated events. Resolution of inflamed tissues to health and homeostasis is an active process mediated by endogenous lipid agonists, including lipoxins and resolvins. This proresolution system appears to be compromised in type 2 diabetes (T2D). The goal of this study was to investigate unresolved inflammation in T2D. Wild-type (WT) and genetically engineered mice, including T2D mice (db/db), transgenic mice overexpressing the human resolvin E1 (RvE1) receptor (ERV1), and a newly bred strain of db/ERV1 mice, were used to determine the impact of RvE1 on the phagocytosis of Porphyromonas gingivalis in T2D. Neutrophils were isolated and incubated with fluorescein isothiocyanate-labeled P. gingivalis, and phagocytosis was measured in a fluorochrome-based assay by flow cytometry. Mitogen-activated protein kinase (MAPK) (p42 and p44) and Akt (Thr308 and Ser473) phosphorylation was analyzed by Western blotting. The mouse dorsal air pouch model was used to evaluate the in vivo impact of RvE1. Results revealed that RvE1 increased the neutrophil phagocytosis of P. gingivalis in WT animals but had no impact in db/db animals. In ERV1-transgenic and ERV1-transgenic diabetic mice, phagocytosis was significantly increased. RvE1 decreased Akt and MAPK phosphorylation in the transgenic animals. In vivo dorsal air pouch studies revealed that RvE1 decreases neutrophil influx into the pouch and increases neutrophil phagocytosis of P. gingivalis in the transgenic animals; cutaneous fat deposition was reduced, as was macrophage infiltration. The results suggest that RvE1 rescues impaired neutrophil phagocytosis in obese T2D mice overexpressing ERV1. C1 [Herrera, Bruno S.; Hasturk, Hatice; Kantarci, Alpdogan; Freire, Marcelo O.; Nguyen, Olivia; Kansal, Shevali; Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. RP Van Dyke, TE (reprint author), Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. EM tvandyke@forsyth.org FU USPHS from the National Institutes of Dental and Craniofacial Research [DE015566, DE018917, DE023584]; Sunstar Americas FX This study was supported by USPHS grants DE015566, DE018917, and DE023584 from the National Institutes of Dental and Craniofacial Research. S.K. was supported by an unrestricted educational grant from Sunstar Americas. NR 60 TC 9 Z9 9 U1 1 U2 4 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 FEB PY 2015 VL 83 IS 2 BP 792 EP 801 DI 10.1128/IAI.02444-14 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AZ0ST UT WOS:000347955700033 PM 25486994 ER PT J AU Jin, JO Zhang, W Du, JY Yu, Q AF Jin, Jun-O Zhang, Wei Du, Jiang-yuan Yu, Qing TI BDCA1-Positive Dendritic Cells (DCs) Represent a Unique Human Myeloid DC Subset That Induces Innate and Adaptive Immune Responses to Staphylococcus aureus Infection (vol 82, pg 4466, 2014) SO INFECTION AND IMMUNITY LA English DT Correction C1 [Jin, Jun-O; Zhang, Wei; Du, Jiang-yuan] Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China. [Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. RP Jin, JO (reprint author), Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China. NR 1 TC 0 Z9 0 U1 0 U2 2 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 FEB PY 2015 VL 83 IS 2 BP 849 EP 849 DI 10.1128/IAI.02857-14 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AZ0ST UT WOS:000347955700040 ER PT J AU Cotter, EW Kelly, NR Mitchell, KS Mazzeo, SE AF Cotter, Elizabeth W. Kelly, Nichole R. Mitchell, Karen S. Mazzeo, Suzanne E. TI An Investigation of Body Appreciation, Ethnic Identity, and Eating Disorder Symptoms in Black Women SO JOURNAL OF BLACK PSYCHOLOGY LA English DT Article DE body appreciation; validity; reliability; ethnic identity; eating disorder symptoms ID AFRICAN-AMERICAN COLLEGE; QUESTIONNAIRE EDE-Q; SELF-REPORT QUESTIONNAIRE; THIN-IDEAL; BULIMIC SYMPTOMATOLOGY; CONSTRUCT-VALIDITY; PREVENTION PROGRAM; IMAGE ASSESSMENT; CAUCASIAN WOMEN; NEGATIVE AFFECT AB Positive body image, such as body appreciation or acceptance, has gone largely unexamined in women of color in comparison with more pathological body attitudes. In an effort to promote and extend positive body image research, this study examined the reliability and validity of the Body Appreciation Scale (BAS) in Black college women, as well as the relation between ethnic identity and body appreciation. Participants were 228 Black college women (M age = 19.89, SD = 4.57). The relation between BAS scores and measures of appearance evaluation, self-esteem, Western beauty ideal internalization, eating disordered behavior, and teasing was examined to investigate convergent and divergent validity. Results supported the construct validity of this measure. Similar to previous research, a confirmatory factor analysis supported a unidimensional factor structure. Ethnic identity was moderately, positively associated with body appreciation. Western beauty ideal internalization mediated the relation between ethnic identity and eating, weight, and shape concerns. Overall, findings support the use of the BAS with Black college women. C1 [Cotter, Elizabeth W.; Kelly, Nichole R.; Mazzeo, Suzanne E.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Mitchell, Karen S.] VA Boston Healthcare Syst, Boston, MA USA. [Mitchell, Karen S.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Cotter, EW (reprint author), Virginia Commonwealth Univ, Dept Psychol, 806 W Franklin St,POB 842018, Richmond, VA 23284 USA. EM ecotter@vcu.edu NR 94 TC 2 Z9 2 U1 9 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0095-7984 EI 1552-4558 J9 J BLACK PSYCHOL JI J. Black Psychol. PD FEB PY 2015 VL 41 IS 1 BP 3 EP 25 DI 10.1177/0095798413502671 PG 23 WC Psychology, Multidisciplinary SC Psychology GA AZ1CA UT WOS:000347976700001 ER PT J AU Han, SH Mallampalli, RK AF Han, SeungHye Mallampalli, Rama K. TI The Acute Respiratory Distress Syndrome: From Mechanism to Translation SO JOURNAL OF IMMUNOLOGY LA English DT Review ID ACUTE LUNG INJURY; NEUTROPHIL EXTRACELLULAR TRAPS; MESENCHYMAL STEM-CELLS; PATTERN-RECOGNITION RECEPTORS; DIAGNOSED MULTIPLE-MYELOMA; TOLL-LIKE RECEPTORS; MOLECULAR-PATTERNS; MITOCHONDRIAL-DNA; NLRP3 INFLAMMASOME; UBIQUITIN LIGASE AB The acute respiratory distress syndrome (ARDS) is a form of severe hypoxemic respiratory failure that is characterized by inflammatory injury to the alveolar capillary barrier, with extravasation of protein-rich edema fluid into the airspace. Although many modalities to treat ARDS have been investigated over the past several decades, supportive therapies remain the mainstay of treatment. In this article, we briefly review the definition, epidemiology, and pathophysiology of ARDS and present emerging aspects of ARDS pathophysiology that encompass modulators of the innate immune response, damage signals, and aberrant proteolysis that may serve as a foundation for future therapeutic targets. C1 [Han, SeungHye; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, UPMC Montefiore, Dept Med, Div Pulm Allergy & Crit Care Med, NW 628, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU National Institutes of Health [R01 HL096376, R01 HL097376, R01 HL098174, R01 HL081784, 1UH2HL123502, P01 HL114453]; U.S. Department of Veterans Affairs FX This work was supported by a Merit Review Award from the U.S. Department of Veterans Affairs and National Institutes of Health Grants R01 HL096376, R01 HL097376, R01 HL098174, R01 HL081784, 1UH2HL123502, and P01 HL114453 (to R.K.M.). This material is based upon work that was supported in part by the Biomedical Laboratory Research and Development, Office of Research and Development, Veterans Health Administration, U.S. Department of Veterans Affairs. NR 89 TC 24 Z9 30 U1 5 U2 24 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2015 VL 194 IS 3 BP 855 EP 860 DI 10.4049/jimmunol.1402513 PG 6 WC Immunology SC Immunology GA AZ3NK UT WOS:000348134000003 PM 25596299 ER PT J AU Kant, CD Akiyama, Y Tanaka, K Shea, S Yamada, Y Connolly, SE Marino, J Tocco, G Benichou, G AF Kant, Cavit D. Akiyama, Yoshinobu Tanaka, Katsunori Shea, Susan Yamada, Yohei Connolly, Sarah E. Marino, Jose Tocco, Georges Benichou, Gilles TI Both Rejection and Tolerance of Allografts Can Occur in the Absence of Secondary Lymphoid Tissues SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; B-INDUCING KINASE; DENDRITIC LEUKOCYTES; INDIRECT RECOGNITION; GRAFT-REJECTION; IN-VIVO; INTRAVENOUS-INJECTION; CARDIAC ALLOGRAFTS; SKIN ALLOGRAFTS; SOLUBLE-ANTIGEN AB In this study, we showed that aly/aly mice, which are devoid of lymph nodes and Peyer's patches, acutely rejected fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts also were rejected acutely by splenectomized aly/aly (aly/aly-spl(-)) mice devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8(+) T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected by aly/aly-spl(-) mice. Actually, aly/aly-spl(-) mice that spontaneously accepted a heart allotransplant and displayed donor-specific tolerance also accepted skin grafts from the same, but not a third-party, donor via a mechanism involving CD4(+) regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs. C1 Massachusetts Gen Hosp, Dept Surg, Transplantat Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Benichou, G (reprint author), Massachusetts Gen Hosp, Dept Surg, Thier 807,55 Fruit St, Boston, MA 02114 USA. EM gbenichou@partners.org FU National Institutes of Health [R21AI100278, R03AI094235] FX This work was supported by National Institutes of Health Grants R21AI100278 and R03AI094235 (to G.B.). NR 60 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2015 VL 194 IS 3 BP 1364 EP 1371 DI 10.4049/jimmunol.1401157 PG 8 WC Immunology SC Immunology GA AZ3NK UT WOS:000348134000056 PM 25535285 ER PT J AU Enamandram, M Duncan, LM Kimball, AB AF Enamandram, Monica Duncan, Lyn M. Kimball, Alexandra B. TI Delivering value in dermatology: Insights from skin cancer detection in routine clinical visits SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE basal cell carcinoma; nonmelanoma skin cancer; quality improvement; screening; skin cancer incidence; squamous cell carcinoma; value in health care delivery ID MELANOMA AB Background: There are increasing demands to demonstrate and report on outcomes in dermatology. Skin cancer diagnosis through skin examination has been well studied, and is promising as a value-delivering intervention. Objective: This study seeks to identify the rate of skin cancer diagnosis during routine visits to a large tertiary dermatology clinic. Methods: Medical records of patients presenting for routine dermatologic care at Massachusetts General Hospital between March 28 and September 28, 2012, were retrospectively reviewed. All patients given a diagnosis of nonmelanoma skin cancer (NMSC) confirmed on biopsy specimen were identified. Billing data were used to identify the total number of patients evaluated during the study period. Results: NMSC was diagnosed in 1266 skin biopsy specimens from 1047 (7.0%) of the 14,829 patients who presented for routine care. In all, 55% of patients with NMSC were men (mean age 70 years). Chief symptoms of patients with NMSC included general dermatologic concerns (37%), routine cancer screening (43%), and specific lesion(s) of concern (19%). Limitations: Retrospective design and restriction to a single institution may limit the generalizability of our findings. Conclusion: The incidence of NMSC in routine dermatology is high; these findings validate the value of care provided by dermatologists and highlight the likely increasing need for their diagnostic skills as the population ages in the United States. C1 [Enamandram, Monica; Kimball, Alexandra B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Duncan, Lyn M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM Harvardskinstudies@partners.org NR 13 TC 1 Z9 1 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2015 VL 72 IS 2 BP 310 EP 313 DI 10.1016/j.jaad.2014.10.030 PG 4 WC Dermatology SC Dermatology GA AY9YH UT WOS:000347903200019 PM 25484266 ER PT J AU Sheu, J Hawryluk, EB Guo, DJ London, WB Huang, JT AF Sheu, Johanna Hawryluk, Elena B. Guo, Dongjing London, Wendy B. Huang, Jennifer T. TI Voriconazole phototoxicity in children: A retrospective review SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review DE nonmelanoma skin cancer; pediatrics; photosensitivity; phototoxicity; squamous cell cancer; voriconazole ID SQUAMOUS-CELL CARCINOMA; RECIPIENTS RECEIVING VORICONAZOLE; ORGAN TRANSPLANT RECIPIENTS; TRIAZOLE ANTIFUNGAL AGENT; SKIN-CANCER; PEDIATRIC-PATIENTS; FUNGAL-INFECTIONS; ZYGOMYCOSIS; SURVEILLANCE; PROPHYLAXIS AB Background: Voriconazole, an antifungal agent, is associated with various cutaneous reactions, including phototoxicity, accelerated photoaging, and skin cancer. Incidence and risk factors for these reactions in children have not been well described. Objective: We sought to determine the incidence of and factors associated with phototoxic reactions and nonmelanoma skin cancer in pediatric patients treated with voriconazole. Methods: This was a retrospective analysis of 430 pediatric patients treated with voriconazole between 2003 and 2013 at Boston Children's Hospital. Results: Incidence of phototoxicity was 20% in all children treated with voriconazole and 47% in children treated for 6 months or longer. Factors associated with phototoxicity included white race, cystic fibrosis, cumulative treatment time, and cumulative dose. Four patients (1%) had nonmelanoma skin cancer; all experienced a phototoxic reaction during voriconazole treatment. Of those with phototoxicity, 5% were discontinued on voriconazole, 6% were referred to dermatology, and 26% received counseling about sun protection from their primary physician. Limitations: Our study is limited by its retrospective design and potential referral bias associated with a tertiary-care center. Conclusions: Voriconazole-associated phototoxicity is relatively common in children and may lead to nonmelanoma skin cancer. However, those with phototoxic reactions are often continued on therapy, rarely referred to dermatology, and infrequently counseled on sun protection. C1 [Sheu, Johanna; Hawryluk, Elena B.; London, Wendy B.; Huang, Jennifer T.] Harvard Univ, Sch Med, Boston, MA USA. [Sheu, Johanna; Hawryluk, Elena B.; Huang, Jennifer T.] Boston Childrens Hosp, Dermatol Program, Div Allergy & Immunol, Dept Med, Boston, MA 02115 USA. [Guo, Dongjing; London, Wendy B.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Guo, Dongjing; London, Wendy B.; Huang, Jennifer T.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Huang, JT (reprint author), Boston Childrens Hosp, Dermatol Program, Fegan Sixth Floor,300 Longwood Ave, Boston, MA 02115 USA. EM jennifer.huang@childrens.harvard.edu NR 29 TC 6 Z9 8 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2015 VL 72 IS 2 BP 314 EP 320 DI 10.1016/j.jaad.2014.10.023 PG 7 WC Dermatology SC Dermatology GA AY9YH UT WOS:000347903200020 PM 25481710 ER PT J AU Mossanen, M Calvert, JK Holt, SK James, AC Wright, JL Harper, JD Krieger, JN Gore, JL AF Mossanen, Matthew Calvert, Joshua K. Holt, Sarah K. James, Andrew C. Wright, Jonathan L. Harper, Jonathan D. Krieger, John N. Gore, John L. TI Overuse of Antimicrobial Prophylaxis in Community Practice Urology SO JOURNAL OF UROLOGY LA English DT Article DE urologic surgical procedures; antibiotic prophylaxis; physician's practice patterns; drug resistance; bacterial; quality of health care ID CLOSTRIDIUM-DIFFICILE COLITIS; INFECTION-PREVENTION-PROJECT; LENGTH-OF-STAY; SURGERY; MORTALITY; RISK AB Purpose: We examined index urological surgeries to assess utilization patterns of antimicrobial prophylaxis in a large, community based population. Materials and Methods: From the Premier Perspectives Database we identified patients who underwent inpatient urological surgeries that are considered index procedures by the ABU (American Board of Urology), including radical prostatectomy, partial or radical nephrectomy, radical cystectomy, ureteroscopy, shock wave lithotripsy, transurethral resection of the prostate, percutaneous nephrostolithotomy, transvaginal surgery, inflatable penile prosthesis, brachytherapy, transurethral resection of bladder tumor and cystoscopy. Procedures were identified based on ICD-9 procedure codes for 2007 to 2012. Antimicrobial administration, class and duration were abstracted from patient billing data. The class and duration of antimicrobials concordant with the 2008 AUA Best Practice Policy Statement was used to determine compliance. Results: The overall compliance rate was 53%, ranging from 0.6% for radical cystectomy to 97% for shock wave lithotripsy. Antimicrobial use consistent with AUA Best Practices included the appropriate class in 67% of cases (range 34% to 80%) and the recommended duration in 78% (range 1.2% to 98%). Average prophylaxis duration for procedures for which it is recommended ranged from 1.1 days after brachytherapy to 10.3 days after radical cystectomy. The compliance rate increased from 46% overall in 2007 to 59% overall in 2012. Conclusions: We documented considerable variation in antimicrobial prophylaxis for urological surgery. Compliance with AUA Best Practices increased with time but overall rates remain less than 60%. Efforts are needed to better understand the reasons for variation from recommended antimicrobial prophylaxis for common inpatient urological procedures to help decrease resultant complications and improve outcomes. C1 [Mossanen, Matthew] Univ Washington, Dept Urol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Div Urol, Seattle, WA USA. RP Mossanen, M (reprint author), Univ Washington, Dept Urol, 1959 Northeast Pacific St,BB-1115,Box 356510, Seattle, WA 98195 USA. EM mnmoss@uw.edu FU NIDDK NIH HHS [P01 DK043881] NR 21 TC 10 Z9 10 U1 0 U2 5 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 FEB PY 2015 VL 193 IS 2 BP 543 EP 547 DI 10.1016/j.juro.2014.08.107 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA AY6YZ UT WOS:000347709800042 PM 25196654 ER PT J AU Cooley, CZ Stockmann, JP Armstrong, BD Sarracanie, M Lev, MH Rosen, MS Wald, LL AF Cooley, Clarissa Zimmerman Stockmann, Jason P. Armstrong, Brandon D. Sarracanie, Mathieu Lev, Michael H. Rosen, Matthew S. Wald, Lawrence L. TI Two-Dimensional Imaging in a Lightweight Portable MRI Scanner without Gradient Coils SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE portable MRI; low-field MRI; nonlinear SEMs; Halbach magnet; parallel imaging ID MAGNETIC-RESONANCE; PHASE GRADIENTS; NMR; FIELD; RECONSTRUCTION; ARRAY; DESIGN AB PurposeAs the premiere modality for brain imaging, MRI could find wider applicability if lightweight, portable systems were available for siting in unconventional locations such as intensive care units, physician offices, surgical suites, ambulances, emergency rooms, sports facilities, or rural healthcare sites. MethodsWe construct and validate a truly portable (<100 kg) and silent proof-of-concept MRI scanner which replaces conventional gradient encoding with a rotating lightweight cryogen-free, low-field magnet. When rotated about the object, the inhomogeneous field pattern is used as a rotating spatial encoding magnetic field (rSEM) to create generalized projections which encode the iteratively reconstructed two-dimensional (2D) image. Multiple receive channels are used to disambiguate the nonbijective encoding field. ResultsThe system is validated with experimental images of 2D test phantoms. Similar to other nonlinear field encoding schemes, the spatial resolution is position dependent with blurring in the center, but is shown to be likely sufficient for many medical applications. ConclusionThe presented MRI scanner demonstrates the potential for portability by simultaneously relaxing the magnet homogeneity criteria and eliminating the gradient coil. This new architecture and encoding scheme shows convincing proof of concept images that are expected to be further improved with refinement of the calibration and methodology. Magn Reson Med 73:872-883, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Cooley, Clarissa Zimmerman; Stockmann, Jason P.; Armstrong, Brandon D.; Sarracanie, Mathieu; Rosen, Matthew S.; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Cooley, Clarissa Zimmerman] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Stockmann, Jason P.; Armstrong, Brandon D.; Sarracanie, Mathieu; Rosen, Matthew S.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lev, Michael H.; Rosen, Matthew S.; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA USA. [Wald, Lawrence L.] Harvard MIT Div Hlth Sci Technol, Cambridge, MA USA. RP Cooley, CZ (reprint author), 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM clzimmer@mit.edu RI Wald, Lawrence/D-4151-2009 FU Department of Defense, Defense Medical Research and Development Program, Applied Research and Advanced Technology Development Award [W81XWH-11-2-0076 (DM09094)]; NIH [P41EB015896, T32DC00038]; NIH Blueprint for Neuroscience Research [T90DA022759/R90DA023427] FX Grant sponsor: The Department of Defense, Defense Medical Research and Development Program, Applied Research and Advanced Technology Development Award; Grant number: W81XWH-11-2-0076 (DM09094); Grant sponsor: NIH; Grant numbers: P41EB015896, T32DC00038; Grant sponsor: NIH Blueprint for Neuroscience Research; Grant number: T90DA022759/R90DA023427. NR 36 TC 12 Z9 12 U1 3 U2 14 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 FEB PY 2015 VL 73 IS 2 BP 872 EP 883 DI 10.1002/mrm.25147 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ3PO UT WOS:000348139500048 PM 24668520 ER PT J AU Swanson, RA AF Swanson, Raymond A. TI Brain glycogen - vestigial no more SO METABOLIC BRAIN DISEASE LA English DT Editorial Material ID IN-VIVO; GLUCOSE DEPRIVATION; ENERGY-METABOLISM; CEREBRAL GLYCOGEN; NEURONAL-ACTIVITY; WHITE-MATTER; ASTROCYTES; NEUROTRANSMITTERS; HYPOGLYCEMIA; STIMULATION C1 [Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Swanson, Raymond A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Swanson, RA (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. EM Raymond.Swanson@ucsf.edu NR 24 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 EI 1573-7365 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD FEB PY 2015 VL 30 IS 1 BP 251 EP 253 DI 10.1007/s11011-014-9596-2 PG 3 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AZ2GS UT WOS:000348053100032 PM 25060966 ER PT J AU Delpech, JC Madore, C Joffre, C Aubert, A Kang, JX Nadjar, A Laye, S AF Delpech, Jean-Christophe Madore, Charlotte Joffre, Corinne Aubert, Agnes Kang, Jing Xuan Nadjar, Agnes Laye, Sophie TI Transgenic Increase in n-3/n-6 Fatty Acid Ratio Protects Against Cognitive Deficits Induced by an Immune Challenge through Decrease of Neuroinflammation SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID AGED MICE; MICROGLIAL ACTIVATION; SIGNALING PATHWAY; SICKNESS BEHAVIOR; WATER MAZE; FAT-1 MICE; LIPOPOLYSACCHARIDE; BRAIN; EXPRESSION; MEMORY AB Polyunsaturated fatty acids (PUFAs) display immunomodulatory properties in the brain, n-3 PUFAs being able to reduce inflammation whereas n-6 PUFAs are more pro-inflammatory. It has been extensively demonstrated that exposure to a peripheral immune challenge leads to the production and release of inflammatory mediators in the brain in association with cognitive deficits. The question arises whether n-3 PUFA supplementation could downregulate the brain inflammatory response and subsequent cognitive alterations. In this study, we used a genetically modified mouse line carrying the fat-1 gene from the roundworm Caenorhabditis elegans, encoding an n-3 PUFA desaturase that catalyzes conversion of n-6 into n-3 PUFA. Consequently, these mice display endogenously elevated n-3 PUFA tissue contents. Fat-1 mice or wild-type (WT) littermates were injected peripherally with lipopolysaccharide (LPS), a bacterial endotoxin, to induce an inflammatory episode. Our results showed that LPS altered differently the phenotype of microglia and the expression of cytokines and chemokines in Fat-1 and WT mice. In Fat-1 mice, pro-inflammatory factors synthesis was lowered compared with WT mice, whereas anti-inflammatory mechanisms were favored 24 h after LPS treatment. Moreover, LPS injection impaired spatial memory in WT mice, whereas interestingly, the Fat-1 mice showed normal cognitive performances. All together, these data suggest that the central n-3 PUFA increase observed in Fat-1 mice modulated the brain innate immune system activity, leading to the protection of animals against LPS-induced pro-inflammatory cytokine production and subsequent spatial memory alteration. C1 [Delpech, Jean-Christophe; Madore, Charlotte; Joffre, Corinne; Aubert, Agnes; Nadjar, Agnes; Laye, Sophie] INRA, UMR 1286, F-33076 Bordeaux, France. [Delpech, Jean-Christophe; Madore, Charlotte; Joffre, Corinne; Aubert, Agnes; Nadjar, Agnes; Laye, Sophie] Univ Bordeaux, UMR 1286, Bordeaux, France. [Kang, Jing Xuan] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kang, Jing Xuan] Harvard Univ, Sch Med, Boston, MA USA. RP Laye, S (reprint author), INRA, UMR 1286, F-33076 Bordeaux, France. EM sophie.laye@bordeaux.inra.fr NR 60 TC 18 Z9 19 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2015 VL 40 IS 3 BP 525 EP 536 DI 10.1038/npp.2014.196 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AY6ET UT WOS:000347660900001 PM 25228141 ER PT J AU Jacobs, EG Holsen, LM Lancaster, K Makris, N Whitfield-Gabrieli, S Remington, A Weiss, B Buka, S Klibanski, A Goldstein, JM AF Jacobs, Emily G. Holsen, Laura M. Lancaster, Katie Makris, Nikos Whitfield-Gabrieli, Sue Remington, Anne Weiss, Blair Buka, Stephen Klibanski, Anne Goldstein, Jill M. TI 17 beta-Estradiol Differentially Regulates Stress Circuitry Activity in Healthy and Depressed Women SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-BETA; PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING-FACTOR; FEMALE RHESUS-MONKEYS; ALPHA MESSENGER-RNA; SEX-DIFFERENCES; PREFRONTAL CORTEX; MOOD DISORDERS; PREMENSTRUAL-SYNDROME; MAJOR DEPRESSION AB Many regions within stress neurocircuitry, including the anterior hypothalamus, amygdala, hippocampus, and medial prefrontal cortex, are densely populated with sex steroid receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17 beta-estradiol (E-2) impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol's role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol's role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in E-2 during the menstrual cycle, we conducted a within-person repeated-measures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy control women underwent hormonal evaluations, behavioral testing, and fMRI scanning on two occasions, under low and high E-2 conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E-2 modulates activity across key stress circuitry regions, including bilateral amygdala, hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E-2 conditions were attenuated under high E-2 conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol's actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced sex difference in MDD risk. C1 [Jacobs, Emily G.; Holsen, Laura M.; Remington, Anne; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Boston, MA 02115 USA. [Jacobs, Emily G.; Holsen, Laura M.; Remington, Anne; Weiss, Blair; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Jacobs, Emily G.; Holsen, Laura M.; Makris, Nikos; Goldstein, Jill M.] Harvard Univ, Sch Med, Boston, MA 02120 USA. [Lancaster, Katie] Univ Virginia, Dept Psychol, Charlottesville, VA 22903 USA. [Makris, Nikos; Whitfield-Gabrieli, Sue; Goldstein, Jill M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. [Makris, Nikos; Whitfield-Gabrieli, Sue; Goldstein, Jill M.] MIT, Charlestown, MA USA. [Whitfield-Gabrieli, Sue] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Buka, Stephen] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Klibanski, Anne] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. RP Jacobs, EG (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, One Brigham Circle, Boston, MA 02120 USA. EM egjacobs@nmr.mgh.harvard.edu FU Office for Research on Women's Health (ORWH); National Institute of Mental Health [ORWH-NIMH SCOR P50 MH082679]; NIMH [T32 MH016259]; NICHD (BIRCWH) [K12 HD051959] FX This study was supported by the Office for Research on Women's Health (ORWH) and National Institute of Mental Health (ORWH-NIMH SCOR P50 MH082679; Goldstein, Tobet, Handa, PIs). Dr Jacobs was supported by the NIMH T32 MH016259 and the NICHD (BIRCWH) K12 HD051959. The authors declare no conflict of interest. NR 90 TC 9 Z9 9 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2015 VL 40 IS 3 BP 566 EP 576 DI 10.1038/npp.2014.203 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AY6ET UT WOS:000347660900005 PM 25113601 ER PT J AU Wang, ZH Butner, JD Kerketta, R Cristini, V Deisboeck, TS AF Wang, Zhihui Butner, Joseph D. Kerketta, Romica Cristini, Vittorio Deisboeck, Thomas S. TI Simulating cancer growth with multiscale agent-based modeling SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Mathematical modeling; Signaling pathway; Tumor growth and invasion; Drug discovery; Translational research ID CELLULAR-AUTOMATON MODEL; TUMOR-GROWTH; BREAST-CANCER; LUNG-CANCER; SOLID TUMOR; MATHEMATICAL-MODEL; CROSS-SCALE; EVOLUTION; HYBRID; MIGRATION AB There have been many techniques developed in recent years to in silico model a variety of cancer behaviors. Agent-based modeling is a specific discrete-based hybrid modeling approach that allows simulating the role of diversity in cell populations as well as within each individual cell; it has therefore become a powerful modeling method widely used by computational cancer researchers. Many aspects of tumor morphology including phenotype-changing mutations, the adaptation to microenvironment, the process of angiogenesis, the influence of extracellular matrix, reactions to chemotherapy or surgical intervention, the effects of oxygen and nutrient availability, and metastasis and invasion of healthy tissues have been incorporated and investigated in agent-based models. In this review, we introduce some of the most recent agent-based models that have provided insight into the understanding of cancer growth and invasion, spanning multiple biological scales in time and space, and we further describe several experimentally testable hypotheses generated by those models. We also discuss some of the current challenges of multiscale agent-based cancer models. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Wang, Zhihui; Kerketta, Romica; Cristini, Vittorio] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Butner, Joseph D.; Cristini, Vittorio] Univ New Mexico, Dept Chem Engn, Albuquerque, NM 87131 USA. [Butner, Joseph D.; Cristini, Vittorio] Univ New Mexico, Ctr Biomed Engn, Albuquerque, NM 87131 USA. [Cristini, Vittorio] King Abdulaziz Univ, Fac Sci, Dept Math, Jeddah 21589, Saudi Arabia. [Deisboeck, Thomas S.] ThinkMotu LLC, Wellesley, MA 02481 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM zwang@salud.unm.edu; ts.deisboeck@thinkmotu.com RI Cristini, Vittorio/N-3540-2013; Faculty of, Sciences, KAU/E-7305-2017 FU National Science Foundation [DMS-1263742]; National Institutes of Health Grant (NIH) [1U54CA149196, 1U54CA143837, 1U54CA151668, 1U54CA143907]; University of New Mexico Cancer Center Victor and Ruby Hansen Surface Professorship in Molecular Modeling of Cancer; New Mexico Cancer Nanoscience and Microsystems Training Center (CNTC) fellowship; Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital FX This work has been supported in part by the National Science Foundation Grant DMS-1263742 (Z.W., V.C.), the National Institutes of Health Grant (NIH) 1U54CA149196, 1U54CA143837, 1U54CA151668, and 1U54CA143907 (V.C.), the University of New Mexico Cancer Center Victor and Ruby Hansen Surface Professorship in Molecular Modeling of Cancer (V.C.), the New Mexico Cancer Nanoscience and Microsystems Training Center (CNTC) fellowship (R.K.), and the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital (T.S.D.). Finally, we apologize to our colleagues whose works could not be cited due to space limitations. NR 92 TC 23 Z9 23 U1 3 U2 52 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD FEB PY 2015 VL 30 BP 70 EP 78 DI 10.1016/j.semcancer.2014.04.001 PG 9 WC Oncology SC Oncology GA AZ2UE UT WOS:000348086900009 PM 24793698 ER PT J AU Hafner, S Wagner, K Wepler, M Matallo, J Groger, M McCook, O Scheuerle, A Huber-Lang, M Frick, M Weber, S Stahl, B Jung, B Calzia, E Georgieff, M Moller, P Dietl, P Radermacher, P Wagner, F AF Hafner, Sebastian Wagner, Katja Wepler, Martin Matallo, Jose Groeger, Michael McCook, Oscar Scheuerle, Angelika Huber-Lang, Markus Frick, Manfred Weber, Sandra Stahl, Bettina Jung, Birgit Calzia, Enrico Georgieff, Michael Moeller, Peter Dietl, Paul Radermacher, Peter Wagner, Florian TI PHYSIOLOGICAL AND IMMUNE-BIOLOGICAL CHARACTERIZATION OF A LONG-TERM MURINE MODEL OF BLUNT CHEST TRAUMA SO SHOCK LA English DT Article DE Cytokines; heme oxygenase 1; nuclear factor-kappa B; nitrotyrosine; purinergic receptors; mitochondrial respiration ID INDUCED LUNG INJURY; P2X(7) RECEPTOR; MECHANICAL VENTILATION; EXTRACELLULAR ATP; CONTUSION; MICE; INFLAMMATION; DIAPHRAGM; RESPONSES; CARDIOPULMONARY AB Blunt chest trauma causes pulmonary and systemic inflammation. It is still a matter of debate whether the long-term course of this inflammatory response is associated with persistent impairment of lung function. We hypothesized that an increase of inflammatory biomarkers may still be present at later time points after blunt chest trauma, eventually, despite normalized lung mechanics and gas exchange. Anesthetized spontaneously breathing male C57BL/6J mice underwent a blast waveYinduced blunt chest trauma or sham procedure. Twelve and 24 h later, blood gases and lung mechanics were measured, together with blood, bronchoalveolar lavage (BAL), and tissue cytokine concentrations (multiplex cytokine kit); heme oxygenase 1 (HO-1), activated caspase-3, Bcl-x(L), and Bax expression (Western blotting); nuclear factor-kappa B activation (electrophoretic mobility shift assay); nitrotyrosine formation; and purinergic (P2XR4 and P2XR7) receptor expression (immunohistochemistry). Histological damage was assessed by hematoxylin and eosin and periodic acid-Schiff staining. High-resolution respirometry allowed assessing mitochondrial respiration in diaphragm biopsies. Chest trauma significantly increased tissue and BAL cytokine levels, associated with a significant increase in HO-1, purinergic receptor expression, and tissue nitrotyrosine formation. In contrast, lung mechanics, gas exchange, and histological damage did not show any significant difference between sham and trauma groups. Activation of the immune response remains present at later time points after murine blunt chest trauma. Discordance of the increased local inflammatory response and preserved pulmonary function may be explained by a dissociation of the immune response and lung function, such as previously suggested after experimental sepsis. C1 [Hafner, Sebastian; Wagner, Katja; Matallo, Jose; Groeger, Michael; McCook, Oscar; Weber, Sandra; Stahl, Bettina; Calzia, Enrico; Radermacher, Peter; Wagner, Florian] Univ Ulm Klinikum, Inst Anasthesiol Pathophysiol & Verfahrensentwick, D-89081 Ulm, Germany. [Hafner, Sebastian; Wagner, Katja; Wepler, Martin; Georgieff, Michael; Wagner, Florian] Univ Ulm Klinikum, Anasthesiol Klin, D-89081 Ulm, Germany. [Wepler, Martin] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Scheuerle, Angelika; Moeller, Peter] Univ Ulm Klinikum, Inst Pathol, D-89081 Ulm, Germany. [Huber-Lang, Markus] Univ Ulm Klinikum, Klin Unfallchirurg Hand Plast & Wiederherstellung, D-89081 Ulm, Germany. [Frick, Manfred; Dietl, Paul] Univ Ulm, Inst Allgemeine Physiol, D-89069 Ulm, Germany. [Jung, Birgit] Boehringer Ingelheim Pharma GmbH & Co KG, Dept Pulm Res, Biberach, Germany. RP Radermacher, P (reprint author), Univ Ulm Klinikum, Inst Anasthesiol Pathophysiol & Verfahrensentwick, Helmholtzstr 8-1, D-89081 Ulm, Germany. EM peter.radermacher@uni-ulm.de RI Frick, Manfred/E-1374-2012 FU Ministry of Science, Research, Arts of Baden-Wurttemberg [Az: 32-7533.-6-10/15/5]; Ulm University FX This work was supported by a grant from the Ministry of Science, Research, Arts of Baden-Wurttemberg (Az: 32-7533.-6-10/15/5 to P.R.) and by a grant from Ulm University (3.4S Senior Clinician Scientist to F.W.). NR 37 TC 6 Z9 6 U1 0 U2 2 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 FEB PY 2015 VL 43 IS 2 BP 140 EP 147 DI 10.1097/SHK.0000000000000277 PG 8 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA AZ3PS UT WOS:000348139900007 PM 25526372 ER PT J AU Nassour, I Kautza, B Rubin, M Escobar, D Luciano, J Loughran, P Gomez, H Scott, J Gallo, D Brumfield, J Otterbein, LE Zuckerbraun, BS AF Nassour, Ibrahim Kautza, Benjamin Rubin, Mark Escobar, Daniel Luciano, Jason Loughran, Patricia Gomez, Hernando Scott, Jeffrey Gallo, David Brumfield, John Otterbein, Leo E. Zuckerbraun, Brian S. TI CARBON MONOXIDE PROTECTS AGAINST HEMORRHAGIC SHOCK AND RESUSCITATION-INDUCED MICROCIRCULATORY INJURY AND TISSUE INJURY SO SHOCK LA English DT Article DE Endothelium; carbon monoxide-releasing molecule; sinusoid; adhesion molecule ID HEME OXYGENASE-1; ORGAN FAILURE; P-SELECTIN; EXPRESSION; ACTIVATION; STRESS; APOPTOSIS; ADHESION; LIVER; DYSFUNCTION AB Traumatic injury is a significant cause of morbidity and mortality worldwide. Microcirculatory activation and injury from hemorrhage contribute to organ injury. Many adaptive responses occur within the microcirculatory beds to limit injury including upregulation of heme oxygenase (HO) enzymes, the rate-limiting enzymes in the breakdown of heme to carbon monoxide (CO), iron, and biliverdin. Here we tested the hypothesis that CO abrogates trauma-induced injury and inflammation protecting the microcirculatory beds. Methods: C57Bl/6 mice underwent sham operation or hemorrhagic shock to a mean arterial pressure of 25 mmHg for 120 minutes. Mice were resuscitated with lactated Ringer's at 2x the volume of maximal shed blood. Mice were randomized to receive CO-releasing molecule or inactive CO-releasing molecule at resuscitation. A cohort of mice was pretreated with tin protoporphyrin-IX to inhibit endogenous CO generation by HOs. Primary mouse liver sinusoidal endothelial cells were cultured for in vitro experiments. Results: Carbon monoxide-releasing molecule protected against hemorrhagic shock/resuscitation organ injury and systemic inflammation and reduced hepatic sinusoidal endothelial injury. Inhibition of HO activity with tin protoporphyrin-IX exacerbated liver hepatic sinusoidal injury. Hemorrhagic shock/resuscitation in vivo or cytokine stimulation in vitro resulted in increased endothelial expression of adhesion molecules that was associated with decreased leukocyte adhesion in vivo and in vitro. Conclusions: Hemorrhagic shock/resuscitation is associated with endothelial injury. Heme oxygenase enzymes and CO are involved in part in diminishing this injury and may prove useful as a therapeutic adjunct that can be harnessed to protect against endothelial activation and damage. C1 [Nassour, Ibrahim; Kautza, Benjamin; Rubin, Mark; Escobar, Daniel; Luciano, Jason; Loughran, Patricia; Gomez, Hernando; Brumfield, John; Zuckerbraun, Brian S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Scott, Jeffrey; Gallo, David; Otterbein, Leo E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Brumfield, John; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), F1200PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu OI Nassour, Ibrahim/0000-0002-9845-1074 FU National Institutes of Health [R01 GM082830]; Veterans Affairs Merit Award [1I01BX000566]; Department of Defense [DM102439, 5R01GM088666]; CIMIT Center for Integration of Medicine and Innovative Technology FX This work is supported by National Institutes of Health grants R01 GM082830 (B.S.Z.), Veterans Affairs Merit Award 1I01BX000566 (B.S.Z.), and Department of Defense DM102439 (B.S.Z.), 5R01GM088666 (L.E.O.) and CIMIT Center for Integration of Medicine and Innovative Technology (L.E.O.). NR 34 TC 6 Z9 6 U1 2 U2 11 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 FEB PY 2015 VL 43 IS 2 BP 166 EP 171 DI 10.1097/SHK.0000000000000264 PG 6 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA AZ3PS UT WOS:000348139900010 PM 25243427 ER PT J AU Tian, HJ Li, CS Scott, TP Montgomery, SR Phan, K Lao, LF Zhang, W Li, YW Hayashi, T Takahashi, S Alobaidaan, R Ruangchainikom, M Zhao, KW Brochmann, EJ Murray, SS Wang, JC Daubs, MD AF Tian, Haijun Li, Chen-Shuang Scott, Trevor P. Montgomery, Scott R. Phan, Kevin Lao, Lifeng Zhang, Wei Li, Yawei Hayashi, Tetsuo Takahashi, Shinji Alobaidaan, Raed Ruangchainikom, Monchai Zhao, Ke-Wei Brochmann, Elsa J. Murray, Samuel S. Wang, Jeffrey C. Daubs, Michael D. TI Secreted phosphoprotein 24 kD inhibits nerve root inflammation induced by bone morphogenetic protein-2 SO SPINE JOURNAL LA English DT Article DE Secreted phosphoprotein 24 kD; Bone morphogenetic protein-2; Nerve root inflammation; Spine surgery; Posterior lumbar fusion; Complications ID GENE-RELATED PEPTIDE; BINDING PEPTIDE; SENSORY NEURONS; RODENT MODEL; SURGERY; FUSION; ARTHRODESIS; EXPRESSION; RECOVERY; INJURY AB BACKGROUND CONTEXT: Bone morphogenetic protein-2 (BMP-2) has been used to successfully promote spine fusion, but side-effects including nerve inflammation have been observed. PURPOSE: To investigate the direct neurotoxic effects of BMP-2 and test the hypotheses that the use of BMP binding proteins, such as secreted phosphoprotein 24 kD (Spp24), can reduce or eliminate these effects. STUDY DESIGN: In vitro experiments and in vivo analysis in a rodent model. METHODS: In vitro, dorsal root ganglion cells were cultured in the presence of BMP-2 with and without Spp24 and calcitonin gene-related peptide and Substance P, markers of neuroinflammation, were measured by immunohistochemistry. In vivo, rats underwent a left-sided laminotomy at L5 to expose the S1 nerve root and were randomized into four different groups according to the intervention at the laminotomy site: collagen sponge only (no BMP-2 or Spp24), BMP-2 in a collagen sponge only, BMP-2 in a collagen sponge+an empty collagen sponge to act as a barrier, and BMP-2 in a collagen sponge+Spp24 in a collagen sponge to act as a barrier. Functional evaluation was done using the Basso, Beattie, and Bresnahan scale and immunohistochemical analyses were performed using calcitonin gene-related peptide and Substance P staining. RESULTS: The neuroinflammatory effects of BMP-2 in vitro were ameliorated by the addition of Spp24. Similarly, in vivo, Spp24 reduced the expression of markers on neuroinflammation in animals treated with BMP-2 and also improved the function after BMP-2 administration. CONCLUSIONS: These results confirm that BMP binding proteins have great potential as adjuvant therapies to limit BMP-2 related side-effects in spine surgery. (C) 2015 Elsevier Inc. All rights reserved. C1 [Tian, Haijun] Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Orthopaed Surg, Shanghai 200003, Peoples R China. [Tian, Haijun; Scott, Trevor P.; Montgomery, Scott R.; Phan, Kevin; Lao, Lifeng; Zhang, Wei; Li, Yawei; Hayashi, Tetsuo; Takahashi, Shinji; Alobaidaan, Raed; Ruangchainikom, Monchai] Univ Calif Los Angeles, Dept Orthopaed Surg, Los Angeles, CA 90024 USA. [Li, Chen-Shuang] Peking Univ, Sch & Hosp Stomatol, Dept Orthodont, Beijing 100081, Peoples R China. [Zhao, Ke-Wei; Brochmann, Elsa J.; Murray, Samuel S.] VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA. [Brochmann, Elsa J.; Murray, Samuel S.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA 91343 USA. [Brochmann, Elsa J.; Murray, Samuel S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Wang, Jeffrey C.] Univ So Calif, Keck Sch Med, Dept Orthopaed Surg, Los Angeles, CA 90033 USA. [Daubs, Michael D.] Univ Nevada, Sch Med, Dept Surg, Div Orthopaed Surg, Las Vegas, NV 89102 USA. RP Tian, HJ (reprint author), Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Orthopaed Surg, 415 Fengyang Rd, Shanghai 200003, Peoples R China. EM haijuntianmd@gmail.com FU AO Spine; Dept. VA; AO Foundation; Cervical Spine Research Society; AO Spine of North America FX HT: Nothing to disclose. C-SL: Nothing to disclose. TPS: Nothing to disclose. SRM: Nothing to disclose. KP: Nothing to disclose. LL: Nothing to disclose. WZ: Nothing to disclose. YL: Nothing to disclose. TH: Nothing to disclose. ST: Fellowship Support: AO Spine (B). RA: Nothing to disclose. MR: Nothing to disclose. K-WZ: Nothing to disclose. EJB: Grants: Dept. VA (G, Paid directly to institution). SSM: Grants: Dept. VA (F, Paid directly to institution). JCW: Royalties: Stryker (B), Osprey (C), Aesculap (B), Biomet (F), Amedica (D), Seaspine (D), Synthes (C), Alphatech (E); Stock Ownership: Fziomed (2,500 shares, less than 1%), Alphatech (14,619 shares, less than 1%); Private Investments: Promethean Spine (B investment, less than 1% of entity, unknown amount of shares), Paradigm Spine (B investment, less than 1% of entity, unknown amount of shares), Benevenue (C investment, less than 1% of entity, unknown amount of shares), Nexgen (B investment, less than 1% of entity, unknown amount of shares), Pioneer (B investment, less than 1% of entity, unknown amount of shares), Amedica (D investment, less than 1% of entity, unknown amount of shares), Vertiflex (B investment, less than 1% of entity, unknown amount of shares), Electrocore (C investment, less than 1% of entity, unknown amount of shares), Surgitech (C investment, less than 1% of entity, unknown amount of shares), Axiomed (25,000 shares, less than 1% of entity), VG Innovations (5,000 options, less than 1% of entity), Corespine (2,000 options valued at less than 1% of company), Expanding Ortho (33,000 options valued at less than 1% of company), Syndicom (66,125 shares valued at less than 1% of company), Osprey (10 options, less than 1% of company), Amedica (35,416 options, less than 1% of company), Bone Biologics (51,255 shares, less than 1% of company), Curative Biosciences (1,875 options, less than 1% of company), Pearldriver (25,000 options, less than 1% of company); Board of Directors: NASS (nonfinancial, reimbursement for travel for board meetings), CSRS (nonfinancial, reimbursement for travel for board meetings), AO Foundation (E, combined for honorariums for educational activities and reimbursements for international travel for this nonprofit foundation, which requires me to travel internationally on multiple trips and allows for business class travel on international trips), Collaborative Spine Research Foundation (nonfinancial, reimbursement for travel for board meetings); Fellowship Support: AO Foundation (E, Paid directly to institution). MDD: Grant: Cervical Spine Research Society (C, Paid directly to institution); Royalties: Depuy-Synthes Spine (F); Consulting: Depuy-Synthes Spine (B); Fellowship Support: AO Spine of North America (E, Paid directly to institution). NR 25 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 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD FEB 1 PY 2015 VL 15 IS 2 BP 314 EP 321 DI 10.1016/j.spinee.2014.09.021 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AZ2DX UT WOS:000348045900019 PM 25264179 ER PT J AU Bicket, MC Horowitz, JM Benzon, HT Cohen, SP AF Bicket, Mark C. Horowitz, Joshua M. Benzon, Honorio T. Cohen, Steven P. TI Epidural injections in prevention of surgery for spinal pain: systematic review and meta-analysis of randomized controlled trials SO SPINE JOURNAL LA English DT Review DE Epidural steroid injection; Surgery; Back pain; Radicular pain; Low back pain; Systematic review; Meta-analysis ID LOW-BACK-PAIN; LUMBAR DISC HERNIATION; OUTCOMES-RESEARCH-TRIAL; NERVE ROOT COMPRESSION; STEROID INJECTIONS; DOUBLE-BLIND; RADICULAR PAIN; CORTICOSTEROID INJECTIONS; SUBGROUP-ANALYSIS; TRANSFORAMINAL INJECTION AB BACKGROUND CONTEXT: Low back pain is debilitating and costly, especially for patients not responding to conservative therapy and requiring surgery. PURPOSE: Our objective was to determine whether epidural steroid injections (ESI) have a surgery-sparing effect in patients with spinal pain. STUDY DESIGN/SETTING: The study design was based on a systematic review and meta-analysis. METHODS: Databases searched included Cochrane, PubMed, and EMBASE. The primary analysis evaluated randomized controlled trials (RCTs) in which treatment groups received ESI and control groups underwent control injections. Secondary analyses involved RCTs comparing surgery with ESI, and subgroup analyses of trials comparing surgery with conservative treatment in which the operative disposition of subjects who received ESI were evaluated. RESULTS: Of the 26 total studies included, only those evaluating the effect of ESI on the need for surgery as a primary outcome examined the same patient cohort, providing moderate evidence that patients who received ESI were less likely to undergo surgery than those who received control treatment. For studies examining surgery as a secondary outcome, ESI demonstrated a trend to reduce the need for surgery for short-term (<1 year) outcomes (risk ratio, 0.68; 95% confidence interval, 0.41-1.13; p=.14) but not long-term (>= 1 year) outcomes (0.95, 0.77-1.19, p=.68). Secondary analyses provided low-level evidence suggesting that between one-third and half of patients considering surgery who undergo ESI can avoid surgery. CONCLUSIONS: Epidural steroid injections may provide a small surgery-sparing effect in the short term compared with control injections and reduce the need for surgery in some patients who would otherwise proceed to surgery. (C) 2015 Elsevier Inc. All rights reserved. C1 [Bicket, Mark C.; Horowitz, Joshua M.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Horowitz, Joshua M.] Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. [Benzon, Honorio T.] Northwestern Sch Med, Dept Anesthesiol, Chicago, IL 60611 USA. [Cohen, Steven P.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21029 USA. [Cohen, Steven P.] Walter Reed Natl Mil Med Ctr, Dept Anesthesiol, Bethesda, MD 20889 USA. RP Bicket, MC (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mbicket@partners.org FU Centers for Rehabilitation Sciences Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA [111726] FX The authors would like to acknowledge Lieutenant Colonel Scott R. Griffith, MD, US Army Pain Management Consultant and Walter Reed Pain Medicine Program Director, and Commander Steven Hanling, MD, US Navy Pain Management Consultant and Naval Medical Center-San Diego Pain Medicine Program Director, for their assistance validating the technical quality scale. Neither received compensation for their contribution to this work. This study was funded in part by Grant 111726 of the Centers for Rehabilitation Sciences Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. The funding organization played no role in any of the following aspects of this study: design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. NR 71 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD FEB 1 PY 2015 VL 15 IS 2 BP 348 EP 362 DI 10.1016/j.spinee.2014.10.011 PG 15 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AZ2DX UT WOS:000348045900023 PM 25463400 ER PT J AU Stuckey, DW Hingtgen, SD Karakas, N Rich, BE Shah, K AF Stuckey, Daniel W. Hingtgen, Shawn D. Karakas, Nihal Rich, Benjamin E. Shah, Khalid TI Engineering Toxin-Resistant Therapeutic Stem Cells to Treat Brain Tumors SO STEM CELLS LA English DT Article DE Cytotoxin; Stem cell; Molecular imaging; Glioblastoma; Targeted therapy ID GROWTH-FACTOR RECEPTOR; IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; PHASE-II TRIAL; PSEUDOMONAS EXOTOXIN; RECOMBINANT IMMUNOTOXIN; DIPHTHERIA-TOXIN; GENE-THERAPY; GLIOBLASTOMA-MULTIFORME; CANCER-TREATMENT; HEMATOLOGIC MALIGNANCIES AB Pseudomonas exotoxin (PE) potently blocks protein synthesis by catalyzing the inactivation of elongation factor-2 (EF-2). Targeted PE-cytotoxins have been used as antitumor agents, although their effective clinical translation in solid tumors has been confounded by off-target delivery, systemic toxicity, and short chemotherapeutic half-life. To overcome these limitations, we have created toxin-resistant stem cells by modifying endogenous EF-2, and engineered them to secrete PE-cytotoxins that target specifically expressed (interleukin-13 receptor subunit alpha-2) or overexpressed (epidermal growth factor receptor) in glioblastomas (GBM). Molecular analysis correlated efficacy of PE-targeted cytotoxins with levels of cognate receptor expression, and optical imaging was applied to simultaneously track the kinetics of protein synthesis inhibition and GBM cell viability in vivo. The release of IL13-PE from biodegradable synthetic extracellular matrix (sECM) encapsulated stem cells in a clinically relevant GBM resection model led to increased long-term survival of mice compared to IL13-PE protein infusion. Moreover, multiple patient-derived GBM lines responded to treatment, underscoring its clinical relevance. In sum, integrating stem cell-based engineering, multimodal imaging, and delivery of PE-cytotoxins in a clinically relevant GBM model represents a novel strategy and a potential advancement in GBM therapy. C1 [Stuckey, Daniel W.; Hingtgen, Shawn D.; Karakas, Nihal; Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Boston, MA USA. [Stuckey, Daniel W.; Hingtgen, Shawn D.; Karakas, Nihal; Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Rich, Benjamin E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rich, Benjamin E.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. EM kshah@mgh.harvard.edu FU U.S. National Institutes of Health [R01CA138922, R01CA173077] FX We thank G. Prestwich (University of Utah) and T. Zarembinski (Biotime, Inc.) for providing us with synthetic extracellular matrix gels, G. Mohapatra (Massachusetts General Hospital) for genome sequencing analysis, and Sara Pignatta (Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori) for experimental assistance during the review process. This work was supported by U.S. National Institutes of Health Grants R01CA138922 (K.S.) and R01CA173077 (K.S.). NR 55 TC 6 Z9 7 U1 1 U2 13 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 FEB PY 2015 VL 33 IS 2 BP 589 EP 600 DI 10.1002/stem.1874 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AZ4RW UT WOS:000348211300024 PM 25346520 ER PT J AU Zhu, WB Casper, A Libal, NL Murphy, SJ Bodhankar, S Offner, H Alkayed, NJ AF Zhu, Wenbin Casper, Amanda Libal, Nicole L. Murphy, Stephanie J. Bodhankar, Sheetal Offner, Halina Alkayed, Nabil J. TI Preclinical Evaluation of Recombinant T Cell Receptor Ligand RTL1000 as a Therapeutic Agent in Ischemic Stroke SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Ischemic stroke; Neurobehavioral evaluation; Immunotherapy; Recombinant T cell receptor ligand; HLA-DR2 transgenic mice ID CLASS-II CONSTRUCTS; FUNCTIONAL RECOVERY; MICE; ACTIVATION; MYELIN; RECOMMENDATIONS; INFLAMMATION; LYMPHOCYTES; TOLERANCE; SEVERITY AB Recombinant T cell Receptor Ligand 1000 (RTL1000), a partial human major histocompatibility complex (MHC) molecule coupled to a human myelin peptide, reduces infarct size after experimental stroke in HLA-DRB1*1502 transgenic (DR2-Tg) mice. In this study, we characterized the therapeutic time window of opportunity for RTL1000; we explored the efficacy of a single dose of RTL1000 administration and determined if RTL1000 affords long-term neurobehavioral functional improvement after ischemic stroke. Male DR2-Tg mice underwent 60 min of intraluminal reversible middle cerebral artery occlusion (MCAO). RTL1000 or vehicle was injected 4, 6, or 8 h after MCAO, followed by three daily injections. In the single-dose study, one-time injection of RTL1000 was applied 4 h after MCAO. Cortical, striatal, and hemispheric infarct sizes were measured 24 or 96 h after stroke. Behavioral testing, including neuroscore evaluation, open field, paw preference, and novel object recognition, was performed up to 28 days after stroke. Our data showed that RTL1000 significantly reduced the infarct size 96 h after MCAO when the first injection was given at 4 and 6 h, but not 8 h, after the onset of stroke. A single dose of 400 or 100 mu g RTL1000 also significantly reduced the infarct size 24 h after MCAO. Behavioral testing showed that RTL1000 treatment used 4 h after MCAO improved long-term cognitive outcome 28 days after stroke. Taken together, RTL1000 protects against acute injury if applied within a 6-h time window and improves long-term functional recovery after experimental stroke in DR2-Tg mice. C1 [Zhu, Wenbin; Casper, Amanda; Libal, Nicole L.; Murphy, Stephanie J.; Offner, Halina; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Bodhankar, Sheetal; Offner, Halina; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Murphy, Stephanie J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA. [Bodhankar, Sheetal; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. RP Alkayed, NJ (reprint author), Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. EM alkayedn@ohsu.edu FU NIH [NS076013]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX This work was supported by NIH Grants #NS076013 (STTR) and by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. NR 32 TC 9 Z9 9 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 EI 1868-601X J9 TRANSL STROKE RES JI Transl. Stroke Res. PD FEB PY 2015 VL 6 IS 1 BP 60 EP 68 DI 10.1007/s12975-014-0373-7 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AZ3IT UT WOS:000348121500008 PM 25270354 ER PT J AU Malte, CA Dennis, PA Saxon, AJ McFall, M Carmody, TP Unger, W Beckham, JC AF Malte, Carol A. Dennis, Paul A. Saxon, Andrew J. McFall, Miles Carmody, Timothy P. Unger, William Beckham, Jean C. TI Tobacco use trajectories among a large cohort of treated smokers with posttraumatic stress disorder SO ADDICTIVE BEHAVIORS LA English DT Article DE Smoking cessation; Posttraumatic stress disorder; Veterans; Major depressive disorder; Relapse ID MENTAL-HEALTH-CARE; SMOKING-CESSATION; NICOTINE DEPENDENCE; GENERAL-POPULATION; CIGARETTE-SMOKING; MAJOR DEPRESSION; ELECTRONIC DIARY; FOLLOW-UP; RELAPSE; ABSTINENCE AB Introduction: This study identified distinct tobacco use trajectories across 18 months in 943 veteran smokers with posttraumatic stress disorder (PTSD) in order to describe quit and relapse patterns, examine associations between trajectory groups on baseline characteristics and cessation service utilization, and explore group differences in mental health outcomes. Methods: Veterans who participated in a muldsite, randomized trial of integrated smoking cessation care were grouped using k-means clustering based on reported daily tobacco use between baseline and 18 months. Four trajectory clusters were identified: no reduction (62%), temporary reduction (11%), late sustained reduction (9%) and early sustained reduction (18%). Results: Median quit times in the early, late, temporary, and no reduction groups were 451, 141.5, 97, and 2 days, respectively. Compared to the early reduction group, the temporary reduction group exhibited higher baseline depression (p < 0.01) and anxiety (p < 0.01), but did not differ in treatment received, with both groups attending significantly more cessation visits (p < 0.001) and more likely to receive recommended pharmacotherapy (p < 0.001) than the no reduction group-between baseline and 6 months. The early reduction group exhibited lower depression relative to the no reduction (p < 0.01) and temporary reduction (p < 0.01) groups across all assessments between baseline and 18 months. Differences were not observed between groups in depressive or PTSD symptom change over time between baseline and 18 months. Conclusions: Tobacco use trajectories among treated smokers with PTSD vary distinctly. Characteristics of identified subgroups may lead to targeted interventions among smokers with PTSD and potentially other psychiatric disorders. Published by Elsevier Ltd. C1 [Malte, Carol A.; Saxon, Andrew J.; McFall, Miles] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Dennis, Paul A.] Durham Vet Affairs Med Ctr, Res & Dev Serv, Durham, NC USA. [Saxon, Andrew J.; McFall, Miles] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Carmody, Timothy P.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Carmody, Timothy P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Unger, William] Providence Vet Affairs Med Ctr, Providence, RI USA. [Beckham, Jean C.] Vet Affairs Mid Atlantic Reg Mental Illness Res E, Durham, NC USA. [Beckham, Jean C.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. RP Malte, CA (reprint author), VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, 1660 S Columbian Way,S-116 ATC, Seattle, WA 98108 USA. EM Carol.Malte@va.gov FU U.S. Department of Veterans Affairs, Office of Research and Development Cooperative Studies Program (CSP) [519]; Veterans Affairs Puget Sound Center of Excellence in Substance Abuse Treatment and Education; U.S. Department of Veterans Affairs, Office of Clinical Research and Development; Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center FX This material is based upon work supported by the U.S. Department of Veterans Affairs, Office of Research and Development Cooperative Studies Program (CSP #519). The Veterans Affairs Puget Sound Center of Excellence in Substance Abuse Treatment and Education, the U.S. Department of Veterans Affairs, Office of Clinical Research and Development, and the Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center provided additional support. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U.S. Department of Veterans Affairs. NR 37 TC 1 Z9 1 U1 5 U2 11 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 FEB PY 2015 VL 41 BP 238 EP 246 DI 10.1016/j.addbeh.2014.10.034 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AY3PZ UT WOS:000347496500037 PM 25452071 ER PT J AU Corey, KE Vuppalanchi, R Wilson, LA Cummings, OW Chalasani, N AF Corey, K. E. Vuppalanchi, R. Wilson, L. A. Cummings, O. W. Chalasani, N. CA NASH CRN TI NASH resolution is associated with improvements in HDL and triglyceride levels but not improvement in LDL or non-HDL-C levels SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; FATTY LIVER-DISEASE; CORONARY-HEART-DISEASE; NONALCOHOLIC STEATOHEPATITIS; FOLLOW-UP; RISK; ATHEROSCLEROSIS; DYSLIPIDEMIA; PIOGLITAZONE; PREDICTION AB BackgroundNonalcoholic steatohepatitis (NASH) is associated with dyslipidemia and cardiovascular disease (CVD). AimTo determine the relationship between resolution of NASH and dyslipidemia. MethodsIndividuals in the Pioglitazone vs. Vitamin E vs. Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial with paired liver biopsies and fasting lipid levels were included (N=222). In the PIVENS trial individuals were randomised to pioglitazone 30mg, vitamin E 800IU or placebo for 96weeks. Change in lipid levels at 96weeks was compared between those with and without NASH resolution. ResultsDyslipidemia at baseline was frequent, with low high-density lipoprotein (HDL) (<40mg/dL in men or <50mg/dL in women) in 63%, hypertriglyceridaemia (150mg/dL) in 46%, hypercholesterolaemia (200mg/dL) in 47% and triglycerides (TG)/HDL >5.0 in 25%. Low-density lipoprotein (LD) 160mg/dL was found in 16% and elevated non-HDL cholesterol (non-HDL-C) (130mg/dL) in 73%. HDL increased with NASH resolution but decreased in those without resolution (2.9mg/dL vs. -2.5mg/dL, P<0.001). NASH resolution was associated with significant decreases in TG and TG/HDL ratio compared to those without resolution (TG: -21.1 vs. -2.3mg/dL, P=0.03 and TG/HDL: -0.7 vs. 0.1, P=0.003). Non-HDL-C, LDL and cholesterol decreased over 96weeks in both groups, but there was no significant difference between groups. Treatment group did not impact lipids. ConclusionsNASH resolution is associated with improvements in TG and HDL but not in other cardiovascular disease risk factors including LDL and non-HDL-C levels. Individuals with resolution of NASH may still be at increased risk of cardiovascular disease. identifier: NCT00063622. C1 [Corey, K. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vuppalanchi, R.; Cummings, O. W.; Chalasani, N.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Wilson, L. A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Corey, KE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM kcorey@partners.org RI Vaughn, Ivana/B-6138-2016; OI Vaughn, Ivana/0000-0002-7201-0289; Vuppalanchi, Raj/0000-0003-0637-1577 FU NIH [K23DK099422-0]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Center for Advancing Translational Sciences (NCATS) [UL1TR000439, UL1TR000077, UL1TR000436, UL1TR000150, UL1TR000424, UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004, UL1TR000423, UL1TR000058, UL1TR000067, UL1TR000454] FX Declaration of funding interests: KEC receives support from the NIH K23DK099422-0. The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713) and by the National Center for Advancing Translational Sciences (NCATS) in conduct of NASH CRN Studies (grants UL1TR000439, UL1TR000077, UL1TR000436, UL1TR000150, UL1TR000424, UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004, UL1TR000423, UL1TR000058, UL1TR000067, UL1TR000454). NR 31 TC 6 Z9 6 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 EI 1365-2036 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD FEB PY 2015 VL 41 IS 3 BP 301 EP 309 DI 10.1111/apt.13035 PG 9 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA AY8XZ UT WOS:000347835300006 PM 25429853 ER PT J AU Gottlieb, LM Tirozzi, KJ Manchanda, R Burns, AR Sandel, MT AF Gottlieb, Laura M. Tirozzi, Karen J. Manchanda, Rishi Burns, Abby R. Sandel, Megan T. TI Moving Electronic Medical Records Upstream Incorporating Social Determinants of Health SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID NUTRITION EXAMINATION SURVEY; HOUSEHOLD FOOD INSECURITY; NATIONAL-HEALTH; CHILDREN; BEHAVIOR; ADOLESCENTS; ADULTHOOD; SECURITY; RISKS AB Background: Knowledge of the biological pathways and mechanisms connecting social factors with health has increased exponentially over the past 25 years, yet in most clinical settings, screening and intervention around social determinants of health are not part of standard clinical care. Electronic medical records provide new opportunities for assessing and managing social needs in clinical settings, particularly those serving vulnerable populations. Purpose: To illustrate the feasibility of capturing information and promoting interventions related to social determinants of health in electronic medical records. Methods: Three case studies were examined in which electronic medical records have been used to collect data and address social determinants of health in clinical settings. Results: From these case studies, we identified multiple functions that electronic medical records can perform to facilitate the integration of social determinants of health into clinical systems, including screening, triaging, referring, tracking, and data sharing. Conclusions: If barriers related to incentives, training, and privacy can be overcome, electronic medical record systems can improve the integration of social determinants of health into health care delivery systems. More evidence is needed to evaluate the impact of such integration on health care outcomes before widespread adoption can be recommended. (C) 2015 American Journal of Preventive Medicine C1 [Gottlieb, Laura M.] Univ Calif San Francisco, Sch Med, Dept Family & Community Med, San Francisco, CA 94118 USA. [Burns, Abby R.] Univ Calif Berkeley, Sch Social Welf, Berkeley, CA 94720 USA. [Manchanda, Rishi] HealthBegins, Los Angeles, CA USA. [Manchanda, Rishi] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Tirozzi, Karen J.] Hlth Leads, Res & Dev, Boston, MA USA. [Sandel, Megan T.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Hlth Policy, Natl Ctr Med Legal Partnership, Washington, DC USA. RP Gottlieb, LM (reprint author), Univ Calif San Francisco, Sch Med, 3333 Calif St,Suite 465, San Francisco, CA 94118 USA. EM gottliebl@chc.ucsf.edu FU Lisa and John Pritzker Family Fund; Kresge Foundation; Robert Wood Johnson Foundation FX Laura Gottlieb's work on this project was supported by the Lisa and John Pritzker Family Fund. The funding agency played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Gottlieb is employed by the University of California, San Francisco and is Co-Founder of HealthBegins.; Megan Sandel's work on this project was supported by the Kresge and Robert Wood Johnson Foundations. Neither funding agency played a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Sandel is also Medical Director of the National Center for Medical-Legal Partnership. NR 26 TC 15 Z9 15 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD FEB PY 2015 VL 48 IS 2 BP 215 EP 218 DI 10.1016/j.amepre.2014.07.009 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AZ2YY UT WOS:000348096300015 PM 25217095 ER PT J AU Evans, AT Loeb, KR Shulman, HM Hassan, S Qiu, WC Hockenbery, DM Ioannou, GN Chauncey, TR Gretch, DR McDonald, GB AF Evans, Ashley T. Loeb, Keith R. Shulman, Howard M. Hassan, Sajida Qiu, Wan Chong Hockenbery, David M. Ioannou, George N. Chauncey, Thomas R. Gretch, David R. McDonald, George B. TI Fibrosing Cholestatic Hepatitis C After Hematopoietic Cell Transplantation Report of 3 Fatal Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE hepatitis C virus; fibrosing cholestatic hepatitis; hematopoietic cell transplantation; liver disease; mycophenolate mofetil; in situ hybridization ID BONE-MARROW-TRANSPLANTATION; MYCOPHENOLATE-MOFETIL; VIRUS-INFECTION; LIVER-TRANSPLANTATION; BILIARY OBSTRUCTION; PREVENTION; RECIPIENTS; DISEASE; COMPLICATIONS; TRANSMISSION AB Development of liver disease after hematopoietic cell transplantation is common and the causes diverse. Infection by hepatitis C virus (HCV) can be seen in patients who are chronically infected before transplant or from passage of virus from an infected donor; the normal 10-year course of hepatitis C after transplant is one of waxing and waning of serum aminotransferase enzymes, with little morbidity. In the series of 3 patients reported here, the course of hepatitis C was rapidly fatal, with the onset of jaundice at day 60 to 80 after transplant and liver histology typical of fibrosing cholestatic hepatitis (marked bile ductular proliferation, ballooned hepatocytes, and associated collagenous fibrosis centered around ductules). The bile ductular reaction pattern varied from elongated structures without a recognizable lumen to a pattern of cuboidal cells with a clear lumen. There was significant cholestasis with bile within hepatocytes and canalicular bile plugs. In situ HCV RNA hybridization studies from 1 patient showed a robust infection with high levels of HCV-infected hepatocytes and active viral replication. All 3 patients were on immunosuppressive drugs after transplant, including mycophenolate mofetil (MMF), which irreversibly inhibits inosine monophosphate dehydrogenase, on which T and B lymphocytes are dependent. We speculate that fatal fibrosing cholestatic hepatitis C in these cases was related to the immunosuppressive effects of MMF, as we had not recognized this presentation of HCV infection before the introduction of MMF. C1 [Evans, Ashley T.; Hockenbery, David M.; Ioannou, George N.; Chauncey, Thomas R.; McDonald, George B.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Loeb, Keith R.; Shulman, Howard M.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Qiu, Wan Chong; Gretch, David R.] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. [Loeb, Keith R.; Shulman, Howard M.; Hassan, Sajida; Hockenbery, David M.; McDonald, George B.] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98104 USA. [Ioannou, George N.; Chauncey, Thomas R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP McDonald, GB (reprint author), Fred Hutchinson Canc Res Ctr, Gastroenterol Hepatol Sect D5 114, 1100 Fairview Ave North, Seattle, WA 98109 USA. EM gmcdonal@fhcrc.org NR 38 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2015 VL 39 IS 2 BP 212 EP 220 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA AZ0SP UT WOS:000347955200008 PM 25517948 ER PT J AU Tompkins, RG AF Tompkins, Ronald G. TI Survival From Burns in the New Millennium 70 Years' Experience From a Single Institution SO ANNALS OF SURGERY LA English DT Review DE burn centers; burns; mortality; survival; verification ID STANDARD OPERATING PROCEDURES; PROMPT ESCHAR EXCISION; BENCHMARKING OUTCOMES; PULMONARY-LESIONS; MORTALITY; INJURIES; CHILDREN; THERAPY; PATIENT AB Objective: This review explores the series of published analyses from Massachusetts General Hospital to better understand how changes in medical specialization of burn medicine likely enabled the most important increase in survival from burns in the past 70 years. Background: Seventy years ago, survival from the most serious burn injuries was not possible even in the most advanced countries until critical advances were introduced. Insights into those few medical advances that actually impacted survival might be better understood from the consideration of a continuous series of survival analyses over 7 decades at Massachusetts General Hospital. Methods: Mortality data from previously reported probit and logit analyses from thousands of patients treated at Massachusetts General Hospital were reviewed. A comparison of mortality from these prior mortality analyses from a more recent multicenter study and a national data set was performed. Results: The only giant leap forward in survival occurred during the 1970s, with no improvement during either the preceding or subsequent 30-year intervals. Despite the many modern advances that have been added to the care of these patients since 1984, although these may have represented medical progress, these advances did not impact survival. Conclusions: Survival rates from burn injury may have been maximized by current treatment approaches within medical centers of excellence in burn medicine. Further efforts to improve the quality of life of survivors of burn injury should ultimately have very favorable impact upon the long-term outcomes in these patients who now survive such devastating injuries. C1 [Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA USA. RP Tompkins, RG (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 1302, Boston, MA 02114 USA. EM rtomp-kins@mgh.harvard.edu FU National Institute of General Medical Sciences [P50GM021700, T32GM007035, U54GM062119, R24GM102656, R01GM101401] FX Supported by the following grants from the National Institute of General Medical Sciences: P50GM021700, T32GM007035, U54GM062119, R24GM102656, and R01GM101401. The authors declare no conflicts of interest. NR 29 TC 8 Z9 8 U1 3 U2 8 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 FEB PY 2015 VL 261 IS 2 BP 263 EP 268 DI 10.1097/SLA.0000000000000623 PG 6 WC Surgery SC Surgery GA AY8AP UT WOS:000347777100034 PM 24670865 ER PT J AU Lawson, EH Zingmond, DS Hall, BL Louie, R Brook, RH Ko, CY AF Lawson, Elise H. Zingmond, David S. Hall, Bruce Lee Louie, Rachel Brook, Robert H. Ko, Clifford Y. TI Comparison Between Clinical Registry and Medicare Claims Data on the Classification of Hospital Quality of Surgical Care SO ANNALS OF SURGERY LA English DT Article DE surgery; quality measurement; clinical registry; administrative claims ID POSTOPERATIVE ADVERSE EVENTS; IMPROVEMENT PROGRAM; ADMINISTRATIVE DATA; RISK ADJUSTMENT; HEALTH-CARE; NSQIP; ASSOCIATION; MORTALITY; OUTCOMES; VOLUME AB Objective: To compare the classification of hospital statistical outlier status as better or worse performance than expected for postoperative complications using Medicare claims versus clinical registry data. Background: Controversy remains as to the most favorable data source for measuring postoperative complications for pay-for-performance and public reporting polices. Methods: Patient-level records (2005-2008) were linked between the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and Medicare inpatient claims. Hospital statistical outlier status for better or worse performance than expected was assessed using each data source for superficial surgical site infection (SSI), deep/organ-space SSI, any SSI, urinary tract infection, pneumonia, sepsis, deep venous thrombosis, pulmonary embolism, venous thromboembolism, and myocardial infarction by developing hierarchical multivariable logistic regression models. Kappa statistics and correlation coefficients assessed agreement between the data sources. Results: A total of 192 hospitals with 110,987 surgical patients were included. Agreement on hospital rank for complication rates between Medicare claims and ACS-NSQIP was poor-to-moderate (weighted kappa: 0.18-0.48). Of hospitals identified as statistical outliers for better or worse performance by Medicare claims, 26% were also identified as outliers by ACS-NSQIP. Of outliers identified by ACS-NSQIP, 16% were also identified as outliers by Medicare claims. Agreement between the data sources on hospital outlier status classification was uniformly poor (weighted kappa: -0.02-0.34). Conclusions: Despite using the same statistical methodology with each data source, classification of hospital outlier status as better or worse performance than expected for postoperative complications differed substantially between ACS-NSQIP and Medicare claims. C1 [Lawson, Elise H.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Lawson, Elise H.; Hall, Bruce Lee; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Lawson, Elise H.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Zingmond, David S.; Louie, Rachel; Brook, Robert H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Hall, Bruce Lee] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Hall, Bruce Lee] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Hall, Bruce Lee] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce Lee] Washington Univ, Olin Business Sch, St Louis, MO USA. [Hall, Bruce Lee] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. [Brook, Robert H.] RAND Corp, Santa Monica, CA USA. [Brook, Robert H.] UCLA Jonathan & Karin Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Lawson, EH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM elawson@mednet.ucla.edu FU VA Health Services Research and Development program [RWJ 65-020]; American College of Surgeons through the Robert Wood Johnson Foundation Clinical Scholars Program; Centers for Medicare and Medicaid Services (CMS) FX E.H.L.'s time was supported by the VA Health Services Research and Development program (RWJ 65-020) and the American College of Surgeons through the Robert Wood Johnson Foundation Clinical Scholars Program. This study was funded by a contract from the Centers for Medicare and Medicaid Services (CMS). The remaining authors have nothing to declare. NR 26 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 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD FEB PY 2015 VL 261 IS 2 BP 290 EP 296 DI 10.1097/SLA.0000000000000707 PG 7 WC Surgery SC Surgery GA AY8AP UT WOS:000347777100038 PM 25569029 ER PT J AU Yao, K Liederbach, E Tang, R Lei, L Czechura, T Sisco, M Howard, M Hulick, PJ Winchester, DJ Coopey, SB Smith, BL AF Yao, Katharine Liederbach, Erik Tang, Rong Lei, Lan Czechura, Tomasz Sisco, Mark Howard, Michael Hulick, Peter J. Winchester, David J. Coopey, Suzanne B. Smith, Barbara L. TI Nipple-Sparing Mastectomy in BRCA1/2 Mutation Carriers: An Interim Analysis and Review of the Literature SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID BILATERAL PROPHYLACTIC MASTECTOMY; RISK-REDUCING SURGERY; BREAST-CANCER; AREOLA COMPLEX; FAMILY-HISTORY; FOLLOW-UP; RECONSTRUCTION; REDUCTION; PREDICTORS; SURVIVAL AB There are few large-scale studies that have examined outcomes for BRCA1/2 carriers who have undergone nipple-sparing mastectomy (NSM). The objective of our study was to examine incidental cancers, operative complications, and locoregional recurrences in BRCA1/2 mutation carriers who underwent NSM for both risk reduction and cancer treatment. This was a retrospective review of pathology results and outcomes of 201 BRCA1/2 carriers from two different institutions who underwent NSM from 2007 to 2014. NSM was performed in 397 breasts of 201 BRCA1/2 carriers. One hundred and twenty-five (62.2 %) patients had a BRCA1 mutation and 76 (37.8 %) had a BRCA2 mutation; 150 (74.6 %) patients underwent NSM for risk reduction and 51 (25.4 %) for cancer. Incidental cancers were found in four (2.7 %) of the 150 risk-reduction patients and two (3.9 %) of the 51 cancer patients. The nipple-areolar complex (NAC) was involved with cancer in three (5.8 %) patients. No prophylactic mastectomy had a positive NAC margin. There was loss of the NAC in seven breasts (1.8 %) and flap necrosis in ten (2.5 %) breasts. With a mean follow-up of 32.6 months (1-76 months), there have been four cancer events-three in cancer patients and one in a risk-reduction patient but none at the NAC. NSM in BRCA1/2 carriers is associated with a low rate of complications and locoregional recurrence but these patients require long-term follow-up in both the cancer and risk-reduction setting. C1 [Yao, Katharine; Liederbach, Erik; Czechura, Tomasz; Sisco, Mark; Howard, Michael; Winchester, David J.] NorthShore Univ HealthSyst, Evanston Hosp, Dept Surg, Evanston, IL 60201 USA. [Hulick, Peter J.] NorthShore Univ HealthSyst, Ctr Med Genet, Dept Med, Evanston, IL USA. [Tang, Rong; Lei, Lan; Coopey, Suzanne B.; Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Yao, Katharine; Sisco, Mark; Howard, Michael; Winchester, David J.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. RP Yao, K (reprint author), NorthShore Univ HealthSyst, Evanston Hosp, Dept Surg, Evanston, IL 60201 USA. EM kyao@northshore.org FU Auxiliary of Evanston Hospital ACE Breast Research Fund; Glenbrook Hospital ACE Breast Research Fund FX The authors acknowledge the Auxiliary of Evanston and Glenbrook Hospitals ACE Breast Research Fund for their generous support of this project through the breast research fellowship program. NR 31 TC 17 Z9 17 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2015 VL 22 IS 2 BP 370 EP 376 DI 10.1245/s10434-014-3883-3 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA AY8QH UT WOS:000347817900006 PM 25023546 ER PT J AU Sheth, RA Feldman, AS Walker, TG AF Sheth, Rahul A. Feldman, Adam S. Walker, T. Gregory TI Renoduodenal Fistula After Transcatheter Embolization of Renal Angiomyolipoma SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Angiomyolipoma; Complication; Embolization ID ARTERIAL EMBOLIZATION; COMPLICATION AB Transcatheter embolization of renal angiomyolipomas is a routinely performed, nephron-sparing procedure with a favorable safety profile. Complications from this procedure are typically minor in severity, with postembolization syndrome the most common minor complication. Abscess formation is a recognized but uncommon major complication of this procedure and is presumably due to superinfection of the infarcted tissue after arterial embolization. In this case report, we describe the formation of a renoduodenal fistula after embolization of an angiomyolipoma, complicated by intracranial abscess formation and requiring multiple percutaneous drainage procedures and eventual partial nephrectomy. C1 [Sheth, Rahul A.; Walker, T. Gregory] Massachusetts Gen Hosp, Div Intervent Radiol, Dept Radiol, Boston, MA 02114 USA. [Feldman, Adam S.] Massachusetts Gen Hosp, Div Urol, Dept Surg, Boston, MA 02114 USA. RP Walker, TG (reprint author), Massachusetts Gen Hosp, Div Intervent Radiol, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM tgwalker@partners.org NR 10 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 EI 1432-086X J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD FEB PY 2015 VL 38 IS 1 BP 232 EP 235 DI 10.1007/s00270-014-0887-0 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AY8RH UT WOS:000347820600030 PM 24722895 ER PT J AU Viaud, S Daillere, R Boneca, IG Lepage, P Langella, P Chamaillard, M Pittet, MJ Ghiringhelli, F Trinchieri, G Goldszmid, R Zitvogel, L AF Viaud, S. Daillere, R. Boneca, I. G. Lepage, P. Langella, P. Chamaillard, M. Pittet, M. J. Ghiringhelli, F. Trinchieri, G. Goldszmid, R. Zitvogel, L. TI Gut microbiome and anticancer immune response: really hot Sh(star)t! SO CELL DEATH AND DIFFERENTIATION LA English DT Review ID INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTORS; GERM-FREE MICE; INDUCED COLITIS; COLON TUMORIGENESIS; BETA-GLUCURONIDASE; COLORECTAL-CANCER; INNATE IMMUNITY; LUNG-CANCER AB The impact of gut microbiota in eliciting innate and adaptive immune responses beneficial for the host in the context of effective therapies against cancer has been highlighted recently. Chemotherapeutic agents, by compromising, to some extent, the intestinal integrity, increase the gut permeability and selective translocation of Gram-positive bacteria in secondary lymphoid organs. There, anticommensal pathogenic Th17 T-cell responses are primed, facilitating the accumulation of Th1 helper T cells in tumor beds after chemotherapy as well as tumor regression. Importantly, the redox equilibrium of myeloid cells contained in the tumor microenvironment is also influenced by the intestinal microbiota. Hence, the anticancer efficacy of alkylating agents (such as cyclophosphamide) and platinum salts (oxaliplatin, cis-platin) is compromised in germ-free mice or animals treated with antibiotics. These findings represent a paradigm shift in our understanding of the mode of action of many compounds having an impact on the host-microbe mutualism. C1 [Viaud, S.; Daillere, R.; Zitvogel, L.] INSERM, Gustave Roussy, U1015, F-94805 Villejuif, France. [Viaud, S.; Daillere, R.; Zitvogel, L.] Univ Paris Sud, Le Kremlin Bicetre, France. [Boneca, I. G.] INSERM, Unit Biol & Genet Bacterial Cell Wall, Paris, France. [Boneca, I. G.] INSERM, Grp Avenir, Paris, France. [Lepage, P.; Langella, P.] Inst Natl Rech Agronom, Micalis UMR1319, Jouy En Josas, France. [Lepage, P.; Langella, P.] AgroParisTech, Micalis UMR1319, F-78350 Jouy En Josas, France. [Chamaillard, M.] Univ Lille Nord France, Lille, France. [Chamaillard, M.] Inst Pasteur, Ctr Infect & Immun Lille, F-59019 Lille, France. [Chamaillard, M.] CNRS, Unite Mixte Rech, Lille, France. [Chamaillard, M.] INSERM, F-59045 Lille, France. [Pittet, M. J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Pittet, M. J.] Harvard Univ, Sch Med, Boston, MA USA. [Ghiringhelli, F.] INSERM, Ctr Georges Francois, U866, Dijon, France. [Ghiringhelli, F.] INSERM, Grp Avenir, Dijon, France. [Ghiringhelli, F.] Univ Bourgogne, Fac Med, Dijon, France. [Trinchieri, G.; Goldszmid, R.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. [Zitvogel, L.] Ctr Invest Clin Biotherapie CICBT 507, Villejuif, France. RP Zitvogel, L (reprint author), INSERM, Gustave Roussy, U1015, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. EM laurence.zitvogel@gustaveroussy.fr RI Chamaillard, Mathias/L-6542-2013; Lepage, Patricia/D-4362-2014; Boneca, Ivo/H-1677-2014 OI Chamaillard, Mathias/0000-0002-0243-9717; Boneca, Ivo/0000-0001-8122-509X FU Institut National du Cancer (INCa); Ligue contre le cancer (LIGUE labellisee); SIRIC Socrate; LABEX; PACRI Onco-Immunology; European Research Council [202283]; ISREC Foundation FX We thank our colleagues from the Gustave Roussy animal facility and Institut Pasteur axenic mice facility. This work was supported by Institut National du Cancer (INCa), la Ligue contre le cancer (LIGUE labellisee), SIRIC Socrate, LABEX and PACRI Onco-Immunology, European Research Council starting grant (PGN from SHAPE to VIR no. 202283 to IGB) and ISREC Foundation. NR 134 TC 19 Z9 21 U1 10 U2 50 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD FEB PY 2015 VL 22 IS 2 SI SI BP 199 EP 214 DI 10.1038/cdd.2014.56 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AY9AR UT WOS:000347842500003 PM 24832470 ER PT J AU Matro, JM Li, T Cristofanilli, M Hughes, ME Ottesen, RA Weeks, JC Wong, YN AF Matro, Jennifer M. Li, Tianyu Cristofanilli, Massimo Hughes, Melissa E. Ottesen, Rebecca A. Weeks, Jane C. Wong, Yu-Ning TI Inflammatory Breast Cancer Management in the National Comprehensive Cancer Network: The Disease, Recurrence Pattern, and Outcome SO CLINICAL BREAST CANCER LA English DT Article DE Brain metastases; Inflammatory breast cancer; Metastatic breast cancer; Multimodality therapy; Triple negative breast cancer ID NERVOUS-SYSTEM METASTASES; CIRCULATING TUMOR-CELLS; BRAIN METASTASES; MULTIMODALITY TREATMENT; PROGNOSTIC FACTORS; NATURAL-HISTORY; SURVIVAL; CARCINOMA; EPIDEMIOLOGY; SITES AB IBC is a unique entity with aggressive clinical features, predictable recurrence patterns, and poor prognosis. The high rate of recurrence, especially in the CNS, suggests that new strategies for surveillance and follow-up are needed for earlier detection or prevention of brain metastases. Background: Inflammatory breast cancer (IBC) is an uncommon clinicopathologic entity characterized by rapid progression and aggressive behavior. We used the National Comprehensive Cancer Network (NCCN) Outcomes Database to characterize recurrence patterns and outcomes. Methods: Patients with newly diagnosed IBC treated between 1999 and 2009 at 12 NCCN institutions were identified, and baseline characteristics were obtained. Patients had multimodality therapy if they received 2 of 3 treatments: surgery, perioperative (neoadjuvant or adjuvant) chemotherapy, or perioperative radiation. The first site of recurrence/metastatic diagnosis was identified. Overall survival was calculated on the basis of stage at diagnosis and receipt of multimodality therapy. Results: We identified 673 patients, of whom 195(29%) had metastatic disease at presentation. Median follow-up was 29 months. Of patients in stage III, 82% received > 1 treatment modality. Among 203 patients in stage III with recurrence, the most frequent sites of first recurrence were bone (28%), central nervous system (CNS), lung, and liver (all 21%). Human epidermal growth factor receptor 2 positive and triple negative subtypes had higher rates of CNS recurrence (P = .001). Median survival was 66 months (95% confidence interval [CI], 54-107) for stage III and 26 months (95% CI, 22-33) for stage IV. Among 82% of patients in stage III receiving multimodality therapy, the median survival was 107 months (95% CI, 71 to not reached). Conclusions: This large, retrospective, multi-institutional study confirms the aggressive clinical features, unique recurrence patterns, and adverse prognosis of IBC. The high rate of CNS recurrence among high-risk subtypes, despite the inflammatory nature of the breast cancer, suggests that new strategies are needed for earlier detection or prevention of brain metastases to improve long-term prognosis. C1 [Matro, Jennifer M.; Li, Tianyu; Wong, Yu-Ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Cristofanilli, Massimo] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Hughes, Melissa E.; Weeks, Jane C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ottesen, Rebecca A.] City Hope Canc Ctr, Duarte, CA USA. RP Matro, JM (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. EM Jennifer.matro@uphs.upenn.edu FU [P30 CA006927]; [K07CA136995-01]; [P50 CA 89393] FX TL, MC, and N-YW were supported by P30 CA006927. N-YW was also supported by K07CA136995-01. Data collection was supported by P50 CA 89393 to Dana Farber Cancer Institute. NR 36 TC 8 Z9 8 U1 0 U2 8 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 EI 1938-0666 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD FEB PY 2015 VL 15 IS 1 BP 1 EP 7 DI 10.1016/j.clbc.2014.05.005 PG 7 WC Oncology SC Oncology GA AZ1QF UT WOS:000348012400001 PM 25034439 ER PT J AU Mayer, EL Gropper, AB Harris, L Gold, JM Parker, L Kuter, I Come, S Najita, JS Guo, H Winer, EP Burstein, HJ AF Mayer, Erica L. Gropper, Adrienne B. Harris, Lyndsay Gold, Julie M. Parker, Leroy Kuter, Irene Come, Steven Najita, Julie S. Guo, Hao Winer, Eric P. Burstein, Harold J. TI Long-Term Follow-Up After Preoperative Trastuzumab and Chemotherapy for HER2-Overexpressing Breast Cancer SO CLINICAL BREAST CANCER LA English DT Article DE Anthracycline; Cardiotoxicity; Neoadjuvant therapy; Pathologic complete response ID SURGICAL ADJUVANT BREAST; PATHOLOGICAL COMPLETE RESPONSE; TRIAL COMPARING DOXORUBICIN; NEOADJUVANT THERAPY; RANDOMIZED-TRIAL; BOWEL PROJECT; SYSTEMIC THERAPY; PLUS TRASTUZUMAB; NSABP B-31; OPEN-LABEL AB Documentation of long-term outcomes following HER2-directed therapy is an emerging research area. We conducted a retrospective analysis of survival and toxicity outcomes using data from early trials of neoadjuvant trastuzumab with chemotherapy. We find that the association between pathologic complete response (pCR) and recurrence-free survival (RFS) persists at long-term follow-up, and that rare late cardiotoxicity might occur in patients re-treated with cardiotoxic agents. Background: Neoadjuvant chemotherapy and trastuzumab is an established treatment for locally advanced HER2-positive breast cancer, providing favorable rates of clinical response and pCR. Minimal data describe long-term outcomes after neoadjuvant HER2-directed therapy. This study aimed to explore long-term efficacy and toxicity after neoadjuvant trastuzumab and chemotherapy for HER2-positive breast cancer. Patients and Methods: Eligible patients participated in 1 of 2 single-arm phase II neoadjuvant trials, receiving either paclitaxel/trastuzumab (TH) or vinorelbine/trastuzumab (NH) for stage II-III HER2-positive disease. Postoperative chemotherapy, with or without trastuzumab, was offered. Charts were reviewed to identify recurrence, death, and treatment-related toxicities. Association of long-term outcomes with baseline characteristics and pathological response to primary therapy was explored. Results: Eighty patients were identified; 33 (41.3%) received TH and 47 (58.8%) received NH. Fourteen (17.5%) had pCR at surgery. Most (96.3%) received anthracycline-based adjuvant chemotherapy; 78.7% of NH patients also received adjuvant trastuzumab. At a median follow-up of 8.8 years, 23 (28.8%) patients have experienced recurrence, with 16 breast cancer-related deaths. Four-year RFS in patients with pCR was 92.9% (95% confidence interval [CI], 79.4%-100%) versus 72.4% without pCR (95% CI, 63.9%-82.1%). All initial symptomatic cardiotoxicity resolved during extended follow-up. New symptomatic cardiotoxicity in long-term follow-up was rare, primarily occurring in patients requiring retreatment with a cardiotoxic agent. Conclusion: Neoadjuvant chemotherapy and trastuzumab for HER2-positive breast cancer resulted in favorable long-term survival with minimal late toxicity. Trends in this data set suggest an association between pCR and improved long-term RFS. Retreatment with cardiotoxic agents might increase risk of late cardiotoxicity. C1 [Mayer, Erica L.; Parker, Leroy; Najita, Julie S.; Guo, Hao; Winer, Eric P.; Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Gropper, Adrienne B.] Brigham & Womens Hosp, Boston, MA USA. [Harris, Lyndsay] Case Comprehens Canc Ctr, Cleveland, OH USA. [Gold, Julie M.] Mt Kisco Med Grp, Mt Kisco, NY USA. [Kuter, Irene] Massachusetts Gen Hosp, Boston, MA USA. [Come, Steven] Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Mayer, EL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM emayer@partners.org RI Guo, Hao/E-8921-2015 OI Guo, Hao/0000-0003-1658-0989 NR 32 TC 3 Z9 3 U1 3 U2 13 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 EI 1938-0666 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD FEB PY 2015 VL 15 IS 1 BP 24 EP 30 DI 10.1016/j.clbc.2014.07.010 PG 7 WC Oncology SC Oncology GA AZ1QF UT WOS:000348012400004 PM 25205424 ER PT J AU Priyadharshini, B Turka, LA AF Priyadharshini, Bhavana Turka, Laurence A. TI T-cell energy metabolism as a controller of cell fate in transplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE AMP-activated protein kinase; immunometabolism; mammalian target of rapamycin; regulatory T cells; transplantation ID DENDRITIC CELLS; ACID-METABOLISM; TRYPTOPHAN CATABOLISM; EFFECTOR FUNCTION; ACTIVATION; MTOR; MEMORY; DIFFERENTIATION; TOLERANCE; PATHWAYS AB Purpose of review To highlight some of the recent developments in the novel field of immunometabolism and the therapeutic potential of the many regulatory components of this immunometabolic network for transplantation. Recent findings In response to cytokines, changes in nutrients, and other alterations in the local milieu, immune cells are capable of changing their internal metabolic pathways to meet their energy demands. Recent studies demonstrate that activated T effectors (Th1 and Th17) are supported by aerobic glycolysis, whereas regulatory T cells and CD8 memory T cells favor fatty acid oxidation and lipid biosynthesis through mitochondrial oxidative phosphorylation. These bioenergetic processes are dependent upon the activation of metabolic sensors such as mammalian target of rapamycin and AMP-activated protein kinase, respectively, indicating that the cross-talk between immunity and metabolism can shape the fate and function of immune cells. Finally, exciting new studies suggest that differences in the bioenergetic mechanisms within the various immune subsets may selectively be exploited for regulating the immune responses. Summary In this review, we will discuss the metabolic signatures adopted by various immune cells during tolerance versus immunity and the promising avenues that can be modulated by targeting metabolic pathways with either nutrition or pharmacological intervention for establishing long-term transplantation tolerance. C1 [Priyadharshini, Bhavana; Turka, Laurence A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Transplantat Sci, Boston, MA USA. RP Turka, LA (reprint author), 149,13th St,Room 5101, Boston, MA 02129 USA. EM lturka@partners.org FU NIH [R21AI105607, P01HL018646] FX This work was funded by the NIH grants R21AI105607 and P01HL018646 (to L.A.T.). NR 53 TC 6 Z9 6 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD FEB PY 2015 VL 20 IS 1 BP 21 EP 28 DI 10.1097/MOT.0000000000000149 PG 8 WC Transplantation SC Transplantation GA AY7DD UT WOS:000347720600004 PM 25563988 ER PT J AU Granados, JMM Benichou, G Kawai, T AF Granados, Jose M. M. Benichou, Gilles Kawai, Tatsuo TI Hematopoietic stem cell infusion/transplantation for induction of allograft tolerance SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE allograft tolerance; chimerism; donor bone marrow transplantation; hematopoietic stem cell transplantation; kidney transplantation; vascularized composite allograft ID BONE-MARROW-TRANSPLANTATION; NONINHERITED MATERNAL ANTIGENS; TOTAL-LYMPHOID IRRADIATION; MISMATCHED RENAL-TRANSPLANTATION; MIXED ALLOGENEIC CHIMERISM; MEMORY T-CELLS; NONHUMAN-PRIMATES; DENDRITIC CELLS; MAINTENANCE IMMUNOSUPPRESSION; KIDNEY-TRANSPLANTATION AB Purpose of review The present review updates the current status of basic, preclinical, and clinical research on donor hematopoietic stem cell infusion for allograft tolerance induction. Recent findings Recent basic studies in mice provide evidence of significant involvement of both central deletional and peripheral regulatory mechanisms in induction and maintenance of allograft tolerance effected through a mixed chimerism approach with donor hematopoietic stem cell infusion. The presence of heterologous memory T cells in primates hampers the induction of persistent chimerism. Durable mixed chimerism, however, now has been recently induced in inbred major histocompatibility complex-mismatched swine, resulting in tolerance of vascularized composite tissue allografts. In clinical transplantation, allograft tolerance has been achieved in human leukocyte antigen-mismatched kidney transplantation after the induction of transient mixed chimerism or persistent full donor chimerism. Summary Tolerance induction in clinical kidney transplantation has been achieved by donor hematopoietic stem cell infusion. Improving the consistency and safety of tolerance induction and extending successful protocols to other organs, and to organs from deceased donors, are critical next steps to bringing tolerance to a wider range of clinical applications. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Transplantat Sci, Boston, MA USA. RP Kawai, T (reprint author), Massachusetts Gen Hosp, Ctr Transplantat Sci, MGH White 521,55 Fruit St, Boston, MA 02114 USA. EM tkawai@mgh.harvard.edu FU NIH [AI102405-01, PO-1 HL 18646-25] FX The present article was supported in part by NIH AI102405-01, PO-1 HL 18646-25. NR 97 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 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD FEB PY 2015 VL 20 IS 1 BP 49 EP 56 DI 10.1097/MOT.0000000000000159 PG 8 WC Transplantation SC Transplantation GA AY7DD UT WOS:000347720600008 PM 25563992 ER PT J AU Wasfy, MM Baggish, AL AF Wasfy, Meagan M. Baggish, Aaron L. TI T-wave inversions in athletes: a sheep in wolf's clothing? SO HEART LA English DT Editorial Material ID EUROPEAN-SOCIETY; CRITERIA; CARDIOLOGY C1 [Wasfy, Meagan M.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. [Baggish, Aaron L.] Harvard Univ, Hlth Serv, Cambridge, MA 02138 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, 55 Fruit St,Yawkey Suite 5B, Boston, MA 02114 USA. EM abaggish@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD FEB 1 PY 2015 VL 101 IS 3 BP 167 EP 168 DI 10.1136/heartjnl-2014-306988 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ1BK UT WOS:000347975200003 PM 25432978 ER PT J AU Berny-Lang, MA Darling, CE Frelinger, AL Barnard, MR Smith, CS Michelson, AD AF Berny-Lang, M. A. Darling, C. E. Frelinger, A. L., III Barnard, M. R. Smith, C. S. Michelson, A. D. TI Do immature platelet levels in chest pain patients presenting to the emergency department aid in the diagnosis of acute coronary syndrome? SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Article DE Acute coronary syndrome; emergency medicine; immature platelet fraction; myocardial infarction; platelets ID DUAL ANTIPLATELET THERAPY; MYOCARDIAL-INFARCTION; RETICULATED PLATELETS; ARTERY-DISEASE; HEART-DISEASE; VOLUME; SIZE; FRACTION; TURNOVER; ASPIRIN AB IntroductionEarly and accurate identification of acute coronary syndrome (ACS) vs. noncardiac chest pain in patients presenting to the emergency department (ED) is problematic and new diagnostic markers are needed. Previous studies reported that elevated mean platelet volume (MPV) is associated with ACS and predictive of cardiovascular risk. MPV is closely related to the immature platelet fraction (IPF), and recent studies have suggested that IPF may be a more sensitive marker of ACS than MPV. The objective of the present study was to determine whether the measurement of IPF assists in the diagnosis of ACS in patients presenting to the ED with chest pain. MethodsIn this single-center, prospective, cross-sectional study, adult patients presenting to the ED with chest pain and/or suspected ACS were considered for enrollment. Blood samples from 236 ACS-negative and 44 ACS-positive patients were analyzed in a Sysmex XE-2100 for platelet count, MPV, IPF, and the absolute count of immature platelets (IPC). ResultsTotal platelet counts, MPV, IPF, and IPC were not statistically different between ACS-negative and ACS-positive patients. The IPF was 4.62.7% and 5.0 +/- 2.8% (mean +/- SD, P=0.24), and the IPC was 10.0 +/- 4.6 and 11.5 +/- 7.5x10(3)/L (P=0.27) for ACS-negative and ACS-positive patients, respectively. ConclusionIn 280 patients presenting to the ED with chest pain and/or suspected ACS, no differences in IPF, IPC or MPV were observed in ACS-negative vs. ACS-positive patients, suggesting that these parameters do not assist in the diagnosis of ACS. C1 [Berny-Lang, M. A.; Frelinger, A. L., III; Barnard, M. R.; Michelson, A. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Boston Childrens Hosp, Ctr Platelet Res Studies,Div Hematol Oncol, Boston, MA 02115 USA. [Darling, C. E.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Smith, C. S.] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA. RP Michelson, AD (reprint author), Boston Childrens Hosp, Karp 08213,300 Longwood Ave, Boston, MA 02115 USA. EM alan.michelson@childrens.harvard.edu FU NIH [5T32HL007574-31]; Society for Academic Emergency Medicine (SAEM), Des Plaines, IL; Sysmex Corporation FX The authors thank Michelle Maynard for excellent technical assistance. MAB was supported by an NIH T32 Training Grant (5T32HL007574-31). CED was supported in part by a Research Training Grant from the Society for Academic Emergency Medicine (SAEM), Des Plaines, IL. This study was funded in part by a grant from Sysmex Corporation; however, Sysmex Corporation had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. NR 34 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-5521 EI 1751-553X J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD FEB PY 2015 VL 37 IS 1 BP 112 EP 119 DI 10.1111/ijlh.12250 PG 8 WC Hematology SC Hematology GA AY9NB UT WOS:000347876600020 PM 24806286 ER PT J AU Goyal, L Wadlow, RC Blaszkowsky, LS Wolpin, BM Abrams, TA McCleary, NJ Sheehan, S Sundaram, E Karol, MD Chen, J Zhu, AX AF Goyal, Lipika Wadlow, Raymond C. Blaszkowsky, Lawrence S. Wolpin, Brian M. Abrams, Thomas A. McCleary, Nadine Jackson Sheehan, Susan Sundaram, Eamala Karol, Michael D. Chen, John Zhu, Andrew X. TI A phase I and pharmacokinetic study of ganetespib (STA-9090) in advanced hepatocellular carcinoma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Hepatocellular carcinoma; STA-9090; Ganetespib; Phase I; Heat shock protein inhibitors; Pharmacokinetics; Hepatic dysfunction ID CELL LUNG-CANCER; HSP90 INHIBITOR; HUMAN LIVER; SORAFENIB; THERAPY; SAFETY; GELDANAMYCIN; DEGRADATION; DOXORUBICIN; EXPRESSION AB Background Ganetespib (STA-9090) is an Hsp90 inhibitor that downregulates VEGFR, c-MET, HER2, IGF-IR, EGFR, and other Hsp90 client proteins involved in hepatocarcinogenesis, thereby making it an attractive therapy for HCC. This Phase I study was performed to establish the safety, tolerability, recommended Phase 2 dose (RP2D), and preliminary clinical activity of ganetespib in previously treated patients with advanced HCC. Methods Patients with advanced HCC, Child-Pugh A cirrhosis, progression on or intolerance to sorafenib, and ECOG PS a parts per thousand currency signaEuro parts per thousand 1 were enrolled in a standard 3x3 dose escalation study at doses of 100 mg/m(2), 150 mg/m(2), and 200 mg/m(2) IV given on days 1, 8, and 15 of each 28-day cycle. Objective response by RECIST version 1.1 criteria was evaluated by CT/MRI every 8 weeks. Results Fourteen patients were enrolled in this trial and received at least one dose of the study drug. Of the 14 patients: median age, 57 years old; male 71 %; Asian 36 %; HCC etiology (HBV 36 %, HCV 43 %, Hemachromatosis 7 %, unknown 21 %); Child Pugh Class (A 93 %, B 7 %); median number of prior treatments 2; median baseline AFP 70.1 ng/mL. The RP2D was determined to be 200 mg/m(2). The most commonly seen AEs were diarrhea (93 %), fatigue (71 %), AST elevation (64 %), and hyperglycemia (64 %). The most common Gr 3/4 AEs were hyperglycemia (21 %) and lipasemia (21 %). One (7 %) patient had a fatal AE, septic shock, within 30 days of receiving the study drug. One dose-limiting toxicity, grade 3 lipasemia, was observed at the 100 mg/m(2) dose. Pharmacokinetics studies showed a t(1/2), CL, T-max, and V-ss of 6.45 h, 48.28 L/h (25.56 L/h/m(2)), 0.76 h, and 191 L (100.4 L/m(2)), respectively. No objective responses were seen; one patient (7 %) had stable disease at 16 weeks. Median time to progression was 1.8 months, and median overall survival was 7.2 months. Conclusion Ganetespib had a manageable safety profile in patients with advanced HCC who had progressed on at least one line of systemic therapy. The pharmacokinetic profile showed that ganetespib exposure in patients with mild hepatic dysfunction is similar to that seen in patients with normal liver function. Ganetespib showed limited clinical benefit in patients with advanced HCC in this phase I trial. C1 [Goyal, Lipika; Blaszkowsky, Lawrence S.; Sheehan, Susan; Sundaram, Eamala; Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Wolpin, Brian M.; Abrams, Thomas A.; McCleary, Nadine Jackson] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goyal, Lipika; Blaszkowsky, Lawrence S.; Wolpin, Brian M.; Abrams, Thomas A.; McCleary, Nadine Jackson; Zhu, Andrew X.] Harvard Univ, Sch Med, Boston, MA USA. [Wadlow, Raymond C.] Virginia Canc Specialists, Fairfax, VA USA. [Karol, Michael D.; Chen, John] Synta Pharmaceut Corp, Lexington, MA USA. RP Goyal, L (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,LH PB 220, Boston, MA 02114 USA. EM lgoyal@partners.org FU Synta Pharmaceuticals FX We received research support for this trial from Synta Pharmaceuticals. NR 37 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2015 VL 33 IS 1 BP 128 EP 137 DI 10.1007/s10637-014-0164-8 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AZ0QI UT WOS:000347949400014 PM 25248753 ER PT J AU Schiff, D Kesari, S de Groot, J Mikkelsen, T Drappatz, J Coyle, T Fichtel, L Silver, B Walters, I Reardon, D AF Schiff, David Kesari, Santosh de Groot, John Mikkelsen, Tom Drappatz, Jan Coyle, Thomas Fichtel, Lisa Silver, Bruce Walters, Ian Reardon, David TI Phase 2 study of CT-322, a targeted biologic inhibitor of VEGFR-2 based on a domain of human fibronectin, in recurrent glioblastoma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Glioblastoma; Adnectin; Anti-angiogenic therapy; VEGF receptor; Irinotecan ID BEVACIZUMAB PLUS IRINOTECAN; ADNECTIN INHIBITOR; TRIAL AB VEGF signaling through VEGFR-2 is the major factor in glioblastoma angiogenesis. CT-322, a pegylated protein engineered from the 10th type III human fibronectin domain, binds the VEGFR-2 extracellular domain with high specificity and affinity to block VEGF-induced VEGFR-2 signaling. This study evaluated CT-322 in an open-label run-in/phase 2 setting to assess its efficacy and safety in recurrent glioblastoma. Eligible patients had 1st, 2nd or 3rd recurrence of glioblastoma with measurable tumor on MRI and no prior anti-angiogenic therapy. The initial CT-322 dose was 1 mg/kg IV weekly, with plans to escalate subsequent patients to 2 mg/kg weekly if tolerated; within each CT-322 dose cohort, patients were randomized to +/- irinotecan IV semiweekly. The primary endpoint was 6-month progression-free survival (PFS-6). Sixty-three patients with a median age of 56 were treated, the majority at first recurrence. One-third experienced serious adverse events, of which four were at least possibly related to study treatment (two intracranial hemorrhages and two infusion reactions). Twenty-nine percent of subjects developed treatment-emergent hypertension. The PFS-6 rate in the CT-322 monotherapy groups was 18.6 and 0.0 % in the 1 and 2 mg/kg treatment groups, respectively; results from the 2 mg/kg group indicated that the null hypothesis that PFS-6 a parts per thousand currency sign12 % could not be rejected. The study was terminated prior to reaching the planned enrollment for all treatment groups because data from the completed CT-322 2 mg/kg monotherapy treatment arm revealed insufficient efficacy. Despite biological activity and a tolerable side effect profile, CT-322 failed to meet the prespecified threshold for efficacy in recurrent glioblastoma. C1 [Schiff, David] Univ Virginia, Neurooncol Ctr, Charlottesville, VA 22908 USA. [Kesari, Santosh; Drappatz, Jan] Dana Farber Canc Inst, Boston, MA 02115 USA. [de Groot, John] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Coyle, Thomas] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Fichtel, Lisa] South Texas Oncol & Hematol, San Antonio, TX USA. [Silver, Bruce] Adnexus, Waltham, MA USA. [Walters, Ian] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Reardon, David] Duke Univ, Durham, NC USA. RP Schiff, D (reprint author), Univ Virginia, Neurooncol Ctr, Box 800432, Charlottesville, VA 22908 USA. EM ds4jd@virginia.edu FU Bristol-Myers-Squibb; Adnexus FX Ian Walters was employed by and owned stock in Bristol-Myers-Squibb at the time of the study, and Bruce Silver was a paid consultant to Bristol-Myers-Squibb and Adnexus. The remaining authors report no conflict of interest. NR 19 TC 8 Z9 8 U1 0 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2015 VL 33 IS 1 BP 247 EP 253 DI 10.1007/s10637-014-0186-2 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AZ0QI UT WOS:000347949400027 PM 25388940 ER PT J AU Courtney, CL Ethun, KF Villinger, F Ruprecht, RM Byrareddy, SN AF Courtney, Cynthia L. Ethun, Kelly F. Villinger, Francois Ruprecht, Ruth M. Byrareddy, Siddappa N. TI Massive occlusive thrombosis of the pulmonary artery in pigtailed macaques chronically infected with R5-tropic simian-human immunodeficiency virus SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE pulmonary arterial hypertension; SHIV; SIV ID VASCULAR-LESIONS; HYPERTENSION; REPLICATION; SIV; ENV AB BackgroundPulmonary arterial hypertension (PAH) has been identified as a serious complication of HIV infection. Methods and ResultsHere, we report sudden death in two pigtailed macaques (Macaca nemestrina) chronically infected (similar to 1-2years post-infection) with an R5 SHIV strain. At necropsy, total occlusion of the pulmonary artery by a large fibrin thrombus was present in both animals. ConclusionThis report describes pulmonary vascular lesions similar to PAH in R5 SHIV-infected pigtail macaques. C1 [Courtney, Cynthia L.; Ethun, Kelly F.; Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Courtney, Cynthia L.; Ethun, Kelly F.; Villinger, Francois; Byrareddy, Siddappa N.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Courtney, Cynthia L.; Ethun, Kelly F.; Villinger, Francois; Byrareddy, Siddappa N.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Ruprecht, Ruth M.] Texas Biomed Res Inst, San Antonio, TX USA. [Ruprecht, Ruth M.; Byrareddy, Siddappa N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ruprecht, Ruth M.; Byrareddy, Siddappa N.] Harvard Univ, Sch Med, Boston, MA USA. RP Byrareddy, SN (reprint author), Emory Univ, Dept Pathol & Lab Med, 101 Woodruff Circle,Room 2337A, Atlanta, GA 30322 USA. EM siddappa.n.byrareddy@emory.edu FU NIH [R21 NS063877, R37 AI034266, P51OD11132] FX The authors thank the animal care and pathology staff of the YNPRC for their excellent care of the animals and technical support for this study. This work was supported by NIH grants R21 NS063877 and R37 AI034266 to RMR as well as base grant P51OD11132 to the Yerkes National Primate Research Center. NR 13 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0047-2565 EI 1600-0684 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB PY 2015 VL 44 IS 1 BP 35 EP 39 DI 10.1111/jmp.12142 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA AY7HU UT WOS:000347732500005 PM 25174584 ER PT J AU Smith, JA Stallons, LJ Collier, JB Chavin, KD Schnellmann, RG AF Smith, Joshua A. Stallons, L. Jay Collier, Justin B. Chavin, Kenneth D. Schnellmann, Rick G. TI Suppression of Mitochondrial Biogenesis through Toll-Like Receptor 4-Dependent Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase Signaling in Endotoxin-Induced Acute Kidney Injury SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ACUTE-RENAL-FAILURE; PERITUBULAR CAPILLARY DYSFUNCTION; ISCHEMIA-REPERFUSION INJURY; CRITICALLY-ILL PATIENTS; MEK1/2 INHIBITOR; TNF-ALPHA; SEPSIS; CELLS; LPS; INFLAMMATION AB Although disruption of mitochondrial homeostasis and biogenesis (MB) is a widely accepted pathophysiologic feature of sepsis-induced acute kidney injury (AKI), the molecular mechanisms responsible for this phenomenon are unknown. In this study, we examined the signaling pathways responsible for the suppression of MB in a mouse model of lipopolysaccharide (LPS)-induced AKI. Downregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), a master regulator of MB, was noted at the mRNA level at 3 hours and protein level at 18 hours in the renal cortex, and was associated with loss of renal function after LPS treatment. LPS-mediated suppression of PGC-1 alpha led to reduced expression of downstream regulators of MB and electron transport chain proteins along with a reduction in renal cortical mitochondrial DNA content. Mechanistically, Toll-like receptor 4 (TLR4) knockout mice were protected from renal injury and disruption of MB after LPS exposure. Immunoblot analysis revealed activation of tumor progression locus 2/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (TPL-2/MEK/ERK) signaling in the renal cortex by LPS. Pharmacologic inhibition of MEK/ERK signaling attenuated renal dysfunction and loss of PGC-1 alpha, and was associated with a reduction in proinflammatory cytokine (e.g., tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta) expression at 3 hours after LPS exposure. Neutralization of TNF-alpha also blocked PGC-1 alpha suppression, but not renal dysfunction, after LPS-induced AKI. Finally, systemic administration of recombinant tumor necrosis factor-alpha alone was sufficient to produce AKI and disrupt mitochondrial homeostasis. These findings indicate an important role for the TLR4/MEK/ERK pathway in both LPS-induced renal dysfunction and suppression of MB. TLR4/MEK/ERK/TNF-alpha signaling may represent a novel therapeutic target to prevent mitochondrial dysfunction and AKI produced by sepsis. C1 [Smith, Joshua A.; Stallons, L. Jay; Collier, Justin B.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Chavin, Kenneth D.] Med Univ S Carolina, Div Transplant Surg, Dept Surg, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health National Institute of General Medical Sciences [GM084147, P20-GM103542-02]; National Institutes of Health National Center for Research Resources [UL1-RR029882, C06-RR015455]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [5I01 BX-000851]; South Carolina Clinical and Translational Research Institute at the Medical University of South Carolina FX This work was supported in part by the National Institutes of Health National Institute of General Medical Sciences [Grants GM084147 (to R.G.S.) and P20-GM103542-02 (to South Carolina COBRE in Oxidants, Redox Balance, and Stress Signaling]; the National Institutes of Health National Center for Research Resources [Grant UL1-RR029882]; the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [Grant 5I01 BX-000851 (to R.G.S.)]; and the South Carolina Clinical and Translational Research Institute at the Medical University of South Carolina. Animal facilities were funded by the National Institutes of Health National Center for Research Resources [Grant C06-RR015455]. NR 59 TC 11 Z9 11 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2015 VL 352 IS 2 BP 346 EP 357 DI 10.1124/jpet.114.221085 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AY8RY UT WOS:000347822200018 PM 25503387 ER PT J AU Chevalier, L Goldfarb, E Miller, J Hoeppner, B Gorrindo, T Birnbaum, RJ AF Chevalier, Lydia Goldfarb, Elizabeth Miller, Jessica Hoeppner, Bettina Gorrindo, Tristan Birnbaum, Robert J. TI Gaps in Preparedness of Clergy and Healthcare Providers to Address Mental Health Needs of Returning Service Members SO JOURNAL OF RELIGION & HEALTH LA English DT Article DE Educational needs assessment; Mixed methods; Post-traumatic stress disorder; Service members; Traumatic brain injury ID POSTTRAUMATIC-STRESS-DISORDER; CORONARY-HEART-DISEASE; VETERANS; DECISIONS; AFGHANISTAN; DISPARITIES; DEPRESSION; TRAUMA; FAITH; PTSD AB To elucidate gaps in the preparedness of clergy and healthcare providers to care for service members (SM) with deployment-related mental health needs. Participants identified clinically relevant symptoms in a standardized video role play of a veteran with deployment-related mental health needs and discussed their preparedness to deal with SM. Clergy members identified suicide and depression most often, while providers identified difficulty sleeping, low energy, nightmares and irritability. Neither clergy nor providers felt prepared to minister to or treat SM with traumatic brain injury. Through a mixed methods approach, we identified gaps in preparedness of clergy and healthcare providers in dealing with the mental health needs of SM. C1 [Chevalier, Lydia; Goldfarb, Elizabeth; Miller, Jessica; Hoeppner, Bettina; Gorrindo, Tristan; Birnbaum, Robert J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hoeppner, Bettina; Gorrindo, Tristan; Birnbaum, Robert J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Chevalier, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Ste 744, Boston, MA 02114 USA. EM lydia.chevalier5@gmail.com NR 26 TC 1 Z9 1 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-4197 EI 1573-6571 J9 J RELIG HEALTH JI J. Relig. Health PD FEB PY 2015 VL 54 IS 1 BP 327 EP 338 DI 10.1007/s10943-014-9917-0 PG 12 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA AY9UL UT WOS:000347895800027 PM 25112409 ER PT J AU Maker, AV Carrara, S Jamieson, NB Pelaez-Luna, M Lennon, AM Dal Molin, M Scarpa, A Frulloni, L Brugge, WR AF Maker, Ajay V. Carrara, Silvia Jamieson, Nigel B. Pelaez-Luna, Mario Lennon, Anne Marie Dal Molin, Marco Scarpa, Aldo Frulloni, Luca Brugge, William R. TI Cyst Fluid Biomarkers for Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Critical Review from the International Expert Meeting on Pancreatic Branch-Duct-Intraductal Papillary Mucinous Neoplasms SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Review ID FINE-NEEDLE-ASPIRATION; HELICOBACTER-PYLORI INFECTION; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; BIOLOGICAL BEHAVIOR; PRECURSOR LESIONS; GNAS MUTATIONS; MESSENGER-RNA; CORE PROTEINS; CELL-LINES C1 [Maker, Ajay V.] Univ Illinois, Dept Surg, Div Surg Oncol, Chicago, IL 60680 USA. [Carrara, Silvia] Ist Clin Humanitas, Digest Endoscopy Unit, Rozzano, Italy. [Jamieson, Nigel B.] Univ Glasgow, Dept Surg, Glasgow G12 8QQ, Lanark, Scotland. [Pelaez-Luna, Mario] Univ Nacl Autonoma Mexico, Dept Gastroenterol, Inst Nacl Ciencias Med & Nutr, Sch Med, Mexico City 04510, DF, Mexico. [Lennon, Anne Marie] Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD USA. [Dal Molin, Marco] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Scarpa, Aldo] Univ Verona, Dept Pathol & Diagnost, I-37100 Verona, Italy. [Frulloni, Luca] Univ Verona, Dept Med, Gastroenterol Sect, I-37100 Verona, Italy. [Brugge, William R.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. RP Maker, AV (reprint author), 835 S Wolcott Ave MC 790, Chicago, IL 60612 USA. EM amaker@uic.edu RI scarpa, aldo/K-6832-2016; OI scarpa, aldo/0000-0003-1678-739X; Frulloni, Luca/0000-0001-7417-2655 FU NCI NIH HHS [R01CA176828, K08 CA190855, R01 CA176828] NR 102 TC 14 Z9 15 U1 1 U2 5 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 FEB PY 2015 VL 220 IS 2 BP 243 EP 253 DI 10.1016/j.jamcollsurg.2014.11.001 PG 11 WC Surgery SC Surgery GA AY9XX UT WOS:000347902000014 PM 25592469 ER PT J AU Lee, KH Haneuse, S Schrag, D Dominici, F AF Lee, Kyu Ha Haneuse, Sebastien Schrag, Deborah Dominici, Francesca TI Bayesian semiparametric analysis of semicompeting risks data: investigating hospital readmission after a pancreatic cancer diagnosis SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Bayesian survival analysis; Illness-death models; Reversible jump Markov chain Monte Carlo methods; Semicompeting risks; Shared frailty ID COMPETING RISKS; MULTISTATE MODELS; RECURRENT EVENTS; TERMINAL EVENTS; UNITED-STATES; ASSOCIATION; SURVIVAL; DEATH AB In the USA, the Centers for Medicare and Medicaid Services use 30-day readmission, following hospitalization, as a proxy outcome to monitor quality of care. These efforts generally focus on treatable health conditions, such as pneumonia and heart failure. Expanding quality-of-care systems to monitor conditions for which treatment options are limited or non-existent, such as pancreatic cancer, is challenging because of the non-trivial force of mortality; 30-day mortality for pancreatic cancer is approximately 30%. In the statistical literature, data that arise when the observation of the time to some non-terminal event is subject to some terminal event are referred to as semicompeting risks data'. Given such data, scientific interest may lie in at least one of three areas: estimation or inference for regression parameters, characterization of dependence between the two events and prediction given a covariate profile. Existing statistical methods focus almost exclusively on the first of these; methods are sparse or non-existent, however, when interest lies with understanding dependence and performing prediction. We propose a Bayesian semiparametric regression framework for analysing semicompeting risks data that permits the simultaneous investigation of all three of the aforementioned scientific goals. Characterization of the induced posterior and posterior predictive distributions is achieved via an efficient Metropolis-Hastings-Green algorithm, which has been implemented in an R package. The framework proposed is applied to data on 16051 individuals who were diagnosed with pancreatic cancer between 2005 and 2008, obtained from Medicare part A. We found that increased risk for readmission is associated with a high comorbidity index, a long hospital stay at initial hospitalization, non-white race, being male and discharge to home care. C1 [Lee, Kyu Ha; Haneuse, Sebastien; Dominici, Francesca] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, KH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM klee@hsph.harvard.edu FU National Cancer Institute [P01 CA134294-02]; National Institutes of Health [ES012044, K18 HS021991, R01 CA181360-01] FX We thank Dr Yun Wang at the Harvard School of Public Heath for assistance and consultation on the Medicare pancreatic cancer data set. We are also grateful for helpful comments from the Joint Editor, an Associate Editor and two referees. This work was supported by National Cancer Institute grant P01 CA134294-02 and National Institutes of Health grants ES012044, K18 HS021991 and R01 CA181360-01. NR 42 TC 7 Z9 7 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0035-9254 EI 1467-9876 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PD FEB PY 2015 VL 64 IS 2 BP 253 EP 273 DI 10.1111/rssc.12078 PG 21 WC Statistics & Probability SC Mathematics GA AY9TM UT WOS:000347893400002 PM 25977592 ER PT J AU Elias, PZ Spector, M AF Elias, Paul Z. Spector, Myron TI Treatment of penetrating brain injury in a rat model using collagen scaffolds incorporating soluble Nogo receptor SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE LA English DT Article DE penetrating brain injury; collagen scaffold; rat brain; Nogo receptor; traumatic brain injury; brain tissue engineering ID SPINAL-CORD-INJURY; AXONAL REGENERATION; MOLECULAR-MECHANISMS; TAU-PROTEIN; IN-VITRO; MACROPHAGES; INFLAMMATION; OLIGODENDROCYTES; DEGENERATION; IMPLANTATION AB Injuries and diseases of the central nervous system (CNS) have the potential to cause permanent loss of brain parenchyma, with severe neurological consequences. Cavitary defects in the brain may afford the possibility of treatment with biomaterials that fill the lesion site while delivering therapeutic agents. This study examined the treatment of penetrating brain injury (PBI) in a rat model with collagen biomaterials and a soluble Nogo receptor (sNgR) molecule. sNgR was aimed at neutralizing myelin proteins that hinder axon regeneration by inducing growth cone collapse. Scaffolds containing sNgR were implanted in the brains of adult rats 1 week after injury and analysed 4 weeks or 8 weeks later. Histological analysis revealed that the scaffolds filled the lesion sites, remained intact with open pores and were infiltrated with cells and extracellular matrix. Immunohistochemical staining demonstrated the composition of the cellular infiltrate to include macrophages, astrocytes and vascular endothelial cells. Isolated regions of the scaffold borders showed integration with surrounding viable brain tissue that included neurons and oligodendrocytes. While axon regeneration was not detected in the scaffolds, the cellular infiltration and vascularization of the lesion site demonstrated a modification of the injury environment with implications for regenerative strategies. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Elias, Paul Z.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Elias, Paul Z.; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA. [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. RP Elias, PZ (reprint author), VA Boston Healthcare Syst, Tissue Engn Labs, Mail Stop 151,Room D1-151,150 S Huntington Ave, Boston, MA 02130 USA. EM pzelias@alum.mit.edu FU US Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service FX The research reported here was supported by the US Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. We thank Dr. Daniel Lee and Dr. Paul Weinreb at Biogen Idec for generously providing the soluble Nogo receptor. We also thank Alix Weaver for assistance with H&E staining. No competing financial interests exist. NR 67 TC 2 Z9 2 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-6254 EI 1932-7005 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD FEB PY 2015 VL 9 IS 2 BP 137 EP 150 DI 10.1002/term.1621 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA AZ0RU UT WOS:000347953100005 PM 23038669 ER PT J AU Stahl, JE AF Stahl, James E. TI Trust and Recognition: Coming to Terms with Models SO MEDICAL DECISION MAKING LA English DT Editorial Material C1 [Stahl, James E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stahl, JE (reprint author), Massachusetts Gen Hosp, MGH Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM jstahl@mgh.harvard.edu NR 6 TC 1 Z9 1 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD FEB PY 2015 VL 35 IS 2 BP 136 EP 138 DI 10.1177/0272989X14563080 PG 3 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AZ2HF UT WOS:000348054300002 PM 25510875 ER PT J AU Enns, EA Cipriano, LE Simons, CT Kong, CY AF Enns, Eva A. Cipriano, Lauren E. Simons, Cyrena T. Kong, Chung Yin TI Identifying Best-Fitting Inputs in Health-Economic Model Calibration: A Pareto Frontier Approach SO MEDICAL DECISION MAKING LA English DT Article DE health-economic model; calibration; Pareto frontier; model uncertainty; parameter uncertainty; parameter estimation; calibration uncertainty ID NATURAL-HISTORY MODEL; MULTIOBJECTIVE GENETIC ALGORITHM; COST-EFFECTIVENESS ANALYSIS; BAYESIAN CALIBRATION; AORTIC-STENOSIS; CERVICAL-CANCER; DISEASE AB Background. To identify best-fitting input sets using model calibration, individual calibration target fits are often combined into a single goodness-of-fit (GOF) measure using a set of weights. Decisions in the calibration process, such as which weights to use, influence which sets of model inputs are identified as best-fitting, potentially leading to different health economic conclusions. We present an alternative approach to identifying best-fitting input sets based on the concept of Pareto-optimality. A set of model inputs is on the Pareto frontier if no other input set simultaneously fits all calibration targets as well or better. Methods. We demonstrate the Pareto frontier approach in the calibration of 2 models: a simple, illustrative Markov model and a previously published cost-effectiveness model of transcatheter aortic valve replacement (TAVR). For each model, we compare the input sets on the Pareto frontier to an equal number of best-fitting input sets according to 2 possible weighted-sum GOF scoring systems, and we compare the health economic conclusions arising from these different definitions of best-fitting. Results. For the simple model, outcomes evaluated over the best-fitting input sets according to the 2 weighted-sum GOF schemes were virtually nonoverlapping on the cost-effectiveness plane and resulted in very different incremental cost-effectiveness ratios ($79,300 [95% CI 72,500-87,600] v. $139,700 [ 95% CI 79,900-182,800] per quality-adjusted life-year [ QALY] gained). Input sets on the Pareto frontier spanned both regions ($79,000 [ 95% CI 64,900-156,200] per QALY gained). The TAVR model yielded similar results. Conclusions. Choices in generating a summary GOF score may result in different health economic conclusions. The Pareto frontier approach eliminates the need to make these choices by using an intuitive and transparent notion of optimality as the basis for identifying best-fitting input sets. C1 [Enns, Eva A.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Cipriano, Lauren E.] Univ Western Ontario, Ivey Business Sch, London, ON, Canada. [Simons, Cyrena T.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Kong, Chung Yin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Kong, Chung Yin] Harvard Univ, Sch Med, Boston, MA USA. RP Kong, CY (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM joey@mgh-ita.org RI Cipriano, Lauren/C-3521-2017 OI Cipriano, Lauren/0000-0001-5568-4516 FU National Cancer Institute [K25CA133141] FX Financial support for this study was provided in part by the National Cancer Institute (K25CA133141). The funding agreement ensured the authors' independence in designing the study, interpreting the data, and writing and publishing the report. Revision accepted for publication 22 February 2014. NR 39 TC 4 Z9 4 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD FEB PY 2015 VL 35 IS 2 BP 170 EP 182 DI 10.1177/0272989X14528382 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AZ2HF UT WOS:000348054300008 PM 24799456 ER PT J AU Codella, J Safdar, N Heffernan, R Alagoz, O AF Codella, James Safdar, Nasia Heffernan, Rick Alagoz, Oguzhan TI An Agent-based Simulation Model for Clostridium difficile Infection Control SO MEDICAL DECISION MAKING LA English DT Article DE Clostridium difficile; simulation methods; agent-based simulation; infectious disease control; hospital-acquired infections ID PSEUDOMEMBRANOUS COLITIS; ORAL VANCOMYCIN; ENVIRONMENTAL SURFACES; HOSPITALIZED-PATIENTS; REDUCE TRANSMISSION; RISK-FACTORS; DISEASE; DIARRHEA; CONTAMINATION; MORTALITY AB Background. Control of Clostridium difficile infection (CDI) is an increasingly difficult problem for health care institutions. There are commonly recommended strategies to combat CDI transmission, such as oral vancomycin for CDI treatment, increased hand hygiene with soap and water for health care workers, daily environmental disinfection of infected patient rooms, and contact isolation of diseased patients. However, the efficacy of these strategies, particularly for endemic CDI, has not been well studied. The objective of this research is to develop a valid, agent-based simulation model (ABM) to study C. difficile transmission and control in a midsized hospital. Methods. We develop an ABM of a midsized hospital with agents such as patients, health care workers, and visitors. We model the natural progression of CDI in a patient using a Markov chain and the transmission of CDI through agent and environmental interactions. We derive input parameters from aggregate patient data from the 2007-2010 Wisconsin Hospital Association and published medical literature. We define a calibration process, which we use to estimate transition probabilities of the Markov model by comparing simulation results to benchmark values found in published literature. Results. In a comparison of CDI control strategies implemented individually, routine bleach disinfection of CDI-positive patient rooms provides the largest reduction in nosocomial asymptomatic colonization (21.8%) and nosocomial CDIs (42.8%). Additionally, vancomycin treatment provides the largest reduction in relapse CDIs (41.9%), CDI-related mortalities (68.5%), and total patient length of stay (21.6%). Conclusion. We develop a generalized ABM for CDI control that can be customized and further expanded to specific institutions and/or scenarios. Additionally, we estimate transition probabilities for a Markov model of natural CDI progression in a patient through calibration. C1 [Codella, James; Alagoz, Oguzhan] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53706 USA. [Heffernan, Rick] Bur Communicable Dis & Emergency Response, Wisconsin Div Publ Hlth, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin Hosp & Clin, Dept Med, Madison, WI 53792 USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Alagoz, O (reprint author), Univ Wisconsin, Dept Ind & Syst Engn, 3242 Mech Engn Bldg,1513 Univ Ave, Madison, WI 53706 USA. EM alagoz@engr.wisc.edu FU CTSA program of NCRR NIH [2UL1TR000427]; National Science Foundation, Division of Civil, Mechanical and Manufacturing Innovation [CMMI-0844423]; VA MERIT award FX Supported through grant 2UL1TR000427 from the CTSA program of NCRR NIH and grant CMMI-0844423 from the National Science Foundation, Division of Civil, Mechanical and Manufacturing Innovation. Nasia Safdar is supported by a VA MERIT award. Revision accepted for publication 18 June 2014. NR 55 TC 3 Z9 3 U1 1 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD FEB PY 2015 VL 35 IS 2 BP 211 EP 229 DI 10.1177/0272989X14545788 PG 19 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AZ2HF UT WOS:000348054300011 PM 25112595 ER PT J AU Carlson, SJ Nandivada, P Chang, MI Mitchell, PD O'Loughlin, A Cowan, E Gura, KM Nose, V Bistrian, BR Puder, M AF Carlson, Sarah J. Nandivada, Prathima Chang, Melissa I. Mitchell, Paul D. O'Loughlin, Alison Cowan, Eileen Gura, Kathleen M. Nose, Vania Bistrian, Bruce R. Puder, Mark TI The addition of medium-chain triglycerides to a purified fish oil-based diet alters inflammatory profiles in mice SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Medium-chain triglycerides; Fish oil; Parenteral nutrition; Inflammation ID TOTAL PARENTERAL-NUTRITION; FATTY-ACID DEFICIENCY; TUMOR-NECROSIS-FACTOR; INTESTINAL FAILURE; ARACHIDONIC-ACID; LIVER-DISEASE; DOCOSAHEXAENOIC ACID; TREATED RATS; GUINEA-PIGS; ENDOTOXIN AB Objective. Parenteral nutrition associated liver disease (PNALD) is a deadly complication of long term parenteral nutrition (PN) use in infants. Fish oil-based lipid emulsion has been shown in recent years to effectively treat PNALD. Alternative fat sources free of essential fatty acids have recently been investigated for health benefits related to decreased inflammatory response. We hypothesized that the addition of medium-chain triglycerides (MCT) to a purified fish oil-based diet would decrease the response to inflammatory challenge in mice, while allowing for sufficient growth and development. Materials/methods. Six groups of ten adult male C57/Bl6 mice were pair-fed different dietary treatments for a period of twelve weeks, varying only in fat source (percent calories by weight): 10.84% soybean oil (SOY), 10% coconut oil (HCO), 10% medium-chain triglycerides (MCI), 3% purified fish oil (PFO), 3% purified fish oil with 3% medium-chain triglycerides (50:50 MCT:PFO) and 3% purified fish oil with 7.59% medium-chain triglycerides (70:30 MCT:PFO). An endotoxin challenge was administered to half of the animals in each group at the completion of dietary treatment. Results. All groups demonstrated normal growth throughout the study period. Groups fed MCT and HCO diets demonstrated biochemical essential fatty acid deficiency and decreased IL-6 and TNF-alpha response to endotoxin challenge. Groups containing PFO had increased inflammatory response to endotoxin challenge, and the addition of MCT to PFO mitigated this inflammatory response. Conclusion. These results suggest that the addition of MCT to PFO formulations may decrease the host response to inflammatory challenge, which may pose potential for optimized PN formulations. Inclusion of MCT in lipid emulsions given with PN formulations may be of use in therapeutic interventions for disease states resulting from chronic inflammation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Carlson, Sarah J.; Nandivada, Prathima; Chang, Melissa I.; O'Loughlin, Alison; Cowan, Eileen; Puder, Mark] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Carlson, Sarah J.; Nandivada, Prathima; Chang, Melissa I.; O'Loughlin, Alison; Cowan, Eileen; Puder, Mark] Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA. [Mitchell, Paul D.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA. [Gura, Kathleen M.] Boston Childrens Hosp, Dept Pharm, Boston, MA USA. [Nose, Vania] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bistrian, Bruce R.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Puder, M (reprint author), 300 Longwood Ave Fegan 3, Boston, MA 02115 USA. EM mark.puder@childrens.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health [F532 HD 071715-02]; National Research Service Award Institutional Training Grant of the National Institutes of Health [2T32DK007754-14, 5 T32 HD007466-16, 5 T32 HD007466-17]; Joshua Ryan Rappaport Research Fellowship; Boston Children's Hospital Department of Surgery; Vascular Biology Program FX Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award number F532 HD 071715-02. Further research support was also given by the National Research Service Award Institutional Training Grant of the National Institutes of Health under award numbers 2T32DK007754-14, 5 T32 HD007466-16 and 5 T32 HD007466-17, the Joshua Ryan Rappaport Research Fellowship, and the Boston Children's Hospital Department of Surgery and the Vascular Biology Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 38 TC 7 Z9 7 U1 2 U2 22 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 FEB PY 2015 VL 64 IS 2 BP 274 EP 282 DI 10.1016/j.metabol.2014.10.005 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AY5CG UT WOS:000347590300016 PM 25458829 ER PT J AU Cote, CJ Sui, JH Anderson, TA Bhattacharya, ST Shank, ES Tuason, PM August, DA Zibaitis, A Firth, PG Fuzaylov, G Leeman, MR Mai, CL Roberts, JD AF Cote, Charles J. Sui, Jinghu Anderson, Thomas Anthony Bhattacharya, Somaletha T. Shank, Erik S. Tuason, Pacifico M. August, David A. Zibaitis, Audrius Firth, Paul G. Fuzaylov, Gennadiy Leeman, Michael R. Mai, Christine L. Roberts, Jesse D., Jr. TI Continuous noninvasive cardiac output in children: is this the next generation of operating room monitors? Initial experience in 402 pediatric patients SO PEDIATRIC ANESTHESIA LA English DT Article DE monitoring; physiologic; cardiac; safety; adverse events; intraoperative ID CONGENITAL HEART-DISEASE; ELECTRICAL VELOCIMETRY; PULSE OXIMETRY; SINGLE-BLIND; ECHOCARDIOGRAPHY; SURGERY; THERMODILUTION; BIOIMPEDANCE; CARDIOMETRY AB BackgroundElectrical Cardiometry (EC) estimates cardiac parameters by measuring changes in thoracic electrical bioimpedance during the cardiac cycle. The ICON (R), using four electrocardiogram electrodes (EKG), estimates the maximum rate of change of impedance to peak aortic blood acceleration (based on the premise that red blood cells change from random orientation during diastole (high impedance) to an aligned state during systole (low impedance)). ObjectiveTo determine whether continuous cardiac output (CO) data provide additional information to current anesthesia monitors that is useful to practitioners. MethodsAfter IRB approval and verbal consent, 402 children were enrolled. Data were uploaded to our anesthesia record at one-minute intervals. Ten-second measurements (averaged over the previous 20 heart beats) were downloaded to separate files for later comparison with routine OR monitors. ResultsData from 374 were in the final cohort (loss of signal or improper lead placement); 292012 measurements during 58049min of anesthesia were made in these children (1day to 19years and 1 to 107kg). Four events had a 25% reduction in cardiac index at least 1min before a clinically important change in other monitored parameters; 18 events in 14 children confirmed manifestations of other hemodynamic measures; eight events may have represented artifacts because the observed measurements did not seem to fit the clinical parameters of the other monitors; three other events documented decreased stroke index with extreme tachycardia. ConclusionsElectrical cardiometry provides real-time cardiovascular information regarding developing hemodynamic events and successfully tracked the rapid response to interventions in children of all sizes. Intervention decisions must be based on the combined data from all monitors and the clinical situation. Our experience suggests that this type of monitor may be an important addition to real-time hemodynamic monitoring. C1 [Cote, Charles J.; Anderson, Thomas Anthony; Bhattacharya, Somaletha T.; Shank, Erik S.; Tuason, Pacifico M.; August, David A.; Zibaitis, Audrius; Firth, Paul G.; Fuzaylov, Gennadiy; Leeman, Michael R.; Mai, Christine L.; Roberts, Jesse D., Jr.] Massachusetts Gen Hosp, MassGen Hosp Children, Dept Anesthesia Crit & Pain Management, Div Pediat Anesthesia, Boston, MA 02114 USA. [Sui, Jinghu] Chinese Acad Med Sci, Plast Surg Hosp, Dept Anesthesiol, Beijing 100730, Peoples R China. RP Cote, CJ (reprint author), Harvard Univ, Sch Med, Div Pediat Anesthesia, MassGen Hosp Children, 55 Fruit St, Boston, MA 02114 USA. EM cjcote@partners.org FU ICON(R) Cardiotronic/ Osypka Medical, Inc., La Jolla, CA FX This study was approved by IRB of the Massachusetts General Hospital Boston MA and FDAAA trial registered (NCT01499615). This research was supported in part through the loan of two devices ICON (R) Cardiotronic/ Osypka Medical, Inc., 7463 Draper Ave, La Jolla, CA 92037, and a research fellow supported by a study grant from the People's Republic of China. NR 31 TC 8 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 EI 1460-9592 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD FEB PY 2015 VL 25 IS 2 BP 150 EP 159 DI 10.1111/pan.12441 PG 10 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA AY8FP UT WOS:000347790200007 PM 24916144 ER PT J AU Schweidenback, CTH Emerman, AB Jambhekar, A Blower, MD AF Schweidenback, Caterina T. H. Emerman, Amy B. Jambhekar, Ashwini Blower, Michael D. TI Evidence for multiple, distinct ADAR-containing complexes in Xenopus laevis SO RNA LA English DT Article DE A-to-I editing; RNA editing; dsRNA; RNP ID DOUBLE-STRANDED-RNA; BICOID MESSENGER-RNA; MAJOR DEVELOPMENTAL TRANSITION; CYTOPLASMIC STRESS GRANULES; FIBROBLAST-GROWTH-FACTOR; LARGE GENE LISTS; ADENOSINE-DEAMINASE; TRANSLATIONAL CONTROL; HUMAN TRANSCRIPTOME; FUNCTIONAL-ANALYSIS AB ADAR (adenosine deaminase acting on RNA) is an RNA-editing enzyme present in most metazoans that converts adenosines in double-stranded RNA targets into inosines. Although the RNA targets of ADAR-mediated editing have been extensively cataloged, our understanding of the cellular function of such editing remains incomplete. We report that long, double-stranded RNA added to Xenopus laevis egg extract is incorporated into an ADAR-containing complex whose protein components resemble those of stress granules. This complex localizes to microtubules, as assayed by accumulation on meiotic spindles. We observe that the length of a double-stranded RNA influences its incorporation into the microtubule-localized complex. ADAR forms a similar complex with endogenous RNA, but the endogenous complex fails to localize to microtubules. In addition, we characterize the endogenous, ADAR-associated RNAs and discover that they are enriched for transcripts encoding transcriptional regulators, zinc-finger proteins, and components of the secretory pathway. Interestingly, association with ADAR correlates with previously reported translational repression in early embryonic development. This work demonstrates that ADAR is a component of two, distinct ribonucleoprotein complexes that contain different types of RNAs and exhibit diverse cellular localization patterns. Our findings offer new insight into the potential cellular functions of ADAR. C1 [Schweidenback, Caterina T. H.; Emerman, Amy B.; Jambhekar, Ashwini; Blower, Michael D.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Schweidenback, Caterina T. H.; Emerman, Amy B.; Jambhekar, Ashwini; Blower, Michael D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Blower, MD (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM blower@molbio.mgh.harvard.edu FU National Institutes of Health (NIH) RO1 [RO1GM086434]; Burroughs Wellcome Fund Career Award in the Biomedical Sciences; NIH [F32 GM090533]; National Science Foundation (NSF) GRFP FX We are grateful to Brenda Bass for generously sharing plasmids, antibodies, and knowledge and to Michael Jantsch, John Sommerville, and Bruce Schnapp for kindly providing antibodies. We thank the MGH Sequencing Core for sequencing our Illumina libraries, members of the Blower laboratory for critically reading this manuscript, and Elijah Carrier for help optimizing Western blot conditions. This research was funded with the following grants: National Institutes of Health (NIH) RO1 (RO1GM086434) (M.D.B.), Burroughs Wellcome Fund Career Award in the Biomedical Sciences (M.D.B.), NIH F32 GM090533 (C.T.H.S.), National Science Foundation (NSF) GRFP (A.B.E.). NR 94 TC 1 Z9 1 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 EI 1469-9001 J9 RNA JI RNA PD FEB PY 2015 VL 21 IS 2 BP 279 EP 295 DI 10.1261/rna.047787.114 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ2AG UT WOS:000348036400012 PM 25519486 ER PT J AU Campbell, JD Liu, G Luo, LQ Xiao, J Gerrein, J Juan-Guardela, B Tedrow, J Alekseyev, YO Yang, IV Correll, M Geraci, M Quackenbush, J Sciurba, F Schwartz, DA Kaminski, N Johnson, WE Monti, S Spira, A Beane, J Lenburg, ME AF Campbell, Joshua D. Liu, Gang Luo, Lingqi Xiao, Ji Gerrein, Joseph Juan-Guardela, Brenda Tedrow, John Alekseyev, Yuriy O. Yang, Ivana V. Correll, Mick Geraci, Mark Quackenbush, John Sciurba, Frank Schwartz, David A. Kaminski, Naftali Johnson, W. Evan Monti, Stefano Spira, Avrum Beane, Jennifer Lenburg, Marc E. TI Assessment of microRNA differential expression and detection in multiplexed small RNA sequencing data SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE microRNA; differential expression; detection; sequencing; multiplexing; coverage ID PATHWAYS AB Small RNA sequencing can be used to gain an unprecedented amount of detail into the microRNA transcriptome. The relatively high cost and low throughput of sequencing bases technologies can potentially be offset by the use of multiplexing. However, multiplexing involves a trade-off between increased number of sequenced samples and reduced number of reads per sample (i.e., lower depth of coverage). To assess the effect of different sequencing depths owing to multiplexing on microRNA differential expression and detection, we sequenced the small RNA of lung tissue samples collected in a clinical setting by multiplexing one, three, six, nine, or 12 samples per lane using the Illumina HiSeq 2000. As expected, the numbers of reads obtained per sample decreased as the number of samples in a multiplex increased. Furthermore, after normalization, replicate samples included in distinct multiplexes were highly correlated (R > 0.97). When detecting differential microRNA expression between groups of samples, microRNAs with average expression >1 reads per million (RPM) had reproducible fold change estimates (signal to noise) independent of the degree of multiplexing. The number of microRNAs detected was strongly correlated with the log(2) number of reads aligning to microRNA loci (R = 0.96). However, most additional microRNAs detected in samples with greater sequencing depth were in the range of expression which had lower fold change reproducibility. These findings elucidate the trade-off between increasing the number of samples in a multiplex with decreasing sequencing depth and will aid in the design of large-scale clinical studies exploring microRNA expression and its role in disease. C1 [Campbell, Joshua D.; Gerrein, Joseph; Johnson, W. Evan; Monti, Stefano; Spira, Avrum; Lenburg, Marc E.] Boston Univ, Bioinformat Grad Program, Boston, MA 02215 USA. [Campbell, Joshua D.; Liu, Gang; Luo, Lingqi; Xiao, Ji; Gerrein, Joseph; Johnson, W. Evan; Monti, Stefano; Spira, Avrum; Beane, Jennifer; Lenburg, Marc E.] Boston Univ, Sect Computat Biomed, Med Ctr, Boston, MA 02118 USA. [Juan-Guardela, Brenda; Tedrow, John; Sciurba, Frank; Kaminski, Naftali] Univ Pittsburgh, Med Ctr, Simmons Ctr Interstitial Lung Dis, Pittsburgh, PA 15213 USA. [Juan-Guardela, Brenda; Tedrow, John; Sciurba, Frank; Kaminski, Naftali] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15213 USA. [Alekseyev, Yuriy O.; Lenburg, Marc E.] Boston Univ, Dept Pathol & Lab Med, Sch Med, Boston, MA 02118 USA. [Yang, Ivana V.; Schwartz, David A.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO 80206 USA. [Yang, Ivana V.; Schwartz, David A.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02215 USA. [Correll, Mick; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Geraci, Mark] Univ Colorado, Dept Med, Sch Med, Aurora, CO 80045 USA. RP Lenburg, ME (reprint author), Boston Univ, Bioinformat Grad Program, Boston, MA 02215 USA. EM mlenburg@bu.edu RI Lenburg, Marc/B-8027-2008; Liu, Geoffrey/N-4421-2016; OI Lenburg, Marc/0000-0002-5760-4708; Beane-Ebel, Jennifer/0000-0002-6699-2132; Gerrein, Joseph/0000-0002-5833-1609 FU National Heart, Lung, and Blood Institute [RC2HL101715-01]; National Cancer Institute's Early Detection Research Network of the National Institutes of Health [U01CA152751] FX We thank the reviewers for their constructive feedback. This work was funded by the National Heart, Lung, and Blood Institute (RC2HL101715-01) and the National Cancer Institute's Early Detection Research Network (U01CA152751) of the National Institutes of Health. NR 14 TC 2 Z9 2 U1 1 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 EI 1469-9001 J9 RNA JI RNA-Publ. RNA Soc. PD FEB PY 2015 VL 21 IS 2 BP 164 EP 171 DI 10.1261/rna.046060.114 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ2AG UT WOS:000348036400002 PM 25519487 ER PT J AU An, G Qin, XQ Acharya, C Xu, Y Deng, SH Shi, LH Zang, MR Sui, WW Yi, SH Li, ZJ Hao, M Feng, XY Jin, FY Zou, DH Qi, JY Zhao, YZ Tai, YT Wang, JX Qiu, LG AF An, Gang Qin, Xiaoqi Acharya, Chirag Xu, Yan Deng, Shuhui Shi, Lihui Zang, Meirong Sui, Weiwei Yi, Shuhua Li, Zengjun Hao, Mu Feng, Xiaoyan Jin, Fengyan Zou, Dehui Qi, Junyuan Zhao, Yaozhong Tai, Yu-Tzu Wang, Jianxing Qiu, Lugui TI Multiple myeloma patients with low proportion of circulating plasma cells had similar survival with primary plasma cell leukemia patients SO ANNALS OF HEMATOLOGY LA English DT Article DE Multiple myeloma; Circulating plasma cells; Primary plasma cell leukemia ID IN-SITU HYBRIDIZATION; WORKING GROUP; INTERGROUPE-FRANCOPHONE; GENETIC ABERRATIONS; TRANSPLANTATION; PREDICTOR; CLASSIFICATION; ABNORMALITIES; PROGRESSION; INTERPHASE AB The common features shared by primary plasma cell leukemia (pPCL) and multiple myeloma (MM) with circulating plasma cells (CPCs) are peripheral blood invasion and expansion of plasma cells independent of the protective bone marrow (BM) microenvironment niche. However, few studies have addressed the relationship between pPCL and MM with CPCs. Here, we quantitated the number CPCs by conventional morphology in 767 patients with newly diagnosed MM; their clinic features were compared with those of 33 pPCL cases. When the presence of CPCs was defined as more than 2 % plasma cells per 100 nucleated cells on Wright-Giemsa stained peripheral blood smears, the incidence of MM with CPCs was 14.1 % in newly diagnosed MM. Patients with CPCs shared many clinical features with pPCL, especially clinical parameters related to tumor burden. However, no commonalities were found in immunophenotyping and cytogenetics. The prognosis of pPCL was poor, with a median progression free survival (PFS) of 12 months and an overall survival (OS) of 15 months. MM patients with CPCs had a clearly inferior PFS and OS as compared with the control cohort. Most interestingly, although the CPCs were not high enough to meet the diagnostic criteria for pPCL, the survival of MM patients with CPCs was comparable with that of pPCL, with a median PFS of 17 months and an OS of 25 months. C1 [An, Gang; Qin, Xiaoqi; Xu, Yan; Deng, Shuhui; Shi, Lihui; Zang, Meirong; Sui, Weiwei; Yi, Shuhua; Li, Zengjun; Hao, Mu; Feng, Xiaoyan; Zou, Dehui; Qi, Junyuan; Zhao, Yaozhong; Wang, Jianxing; Qiu, Lugui] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China. [An, Gang; Qin, Xiaoqi; Xu, Yan; Deng, Shuhui; Shi, Lihui; Zang, Meirong; Sui, Weiwei; Yi, Shuhua; Li, Zengjun; Hao, Mu; Feng, Xiaoyan; Zou, Dehui; Qi, Junyuan; Zhao, Yaozhong; Wang, Jianxing; Qiu, Lugui] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China. [An, Gang; Qin, Xiaoqi; Xu, Yan; Deng, Shuhui; Shi, Lihui; Zang, Meirong; Sui, Weiwei; Yi, Shuhua; Li, Zengjun; Hao, Mu; Feng, Xiaoyan; Zou, Dehui; Qi, Junyuan; Zhao, Yaozhong; Wang, Jianxing; Qiu, Lugui] Peking Union Med Coll, Tianjin, Peoples R China. [Jin, Fengyan] Jilin Univ, Ctr Canc, Hosp 1, Changchun 130023, Peoples R China. [Acharya, Chirag; Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Acharya, Chirag; Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Qiu, LG (reprint author), Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China. EM drqiu99@medmail.com.cn FU National Natural Science Fund [81400175, 81172255, 81370632]; Clinical Research Program from Ministry of Health, China; Special Key Anticancer Research and Development Program of Tianjin Municipality [12ZCDZSY17600]; Union Youth Research Fund of Peking Union Medical College; Doctoral Foundation [20131106120037] FX The present study was supported by the National Natural Science Fund (81400175, 81172255, 81370632), the Clinical Research Program from Ministry of Health, China (Key project 2010 to 2012), the Special Key Anticancer Research and Development Program of Tianjin Municipality (12ZCDZSY17600), the Union Youth Research Fund of Peking Union Medical College (2012-2013), the Doctoral Foundation (20131106120037). NR 27 TC 5 Z9 5 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 EI 1432-0584 J9 ANN HEMATOL JI Ann. Hematol. PD FEB PY 2015 VL 94 IS 2 BP 257 EP 264 DI 10.1007/s00277-014-2211-0 PG 8 WC Hematology SC Hematology GA AY6ML UT WOS:000347680200010 PM 25231928 ER PT J AU Beste, LA Green, PK Ioannou, GN AF Beste, Lauren A. Green, Pamela K. Ioannou, George N. TI Boceprevir and telaprevir-based regimens for the treatment of hepatitis C virus in HIV/HCV coinfected patients SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE hepatitis C virus; hepatitis C virus; HIV; protease inhibitor; veterans ID HUMAN-IMMUNODEFICIENCY-VIRUS; TREATMENT-NAIVE PATIENTS; ALPHA-2A PLUS RIBAVIRIN; HEPATOCELLULAR-CARCINOMA; PEGINTERFERON ALPHA-2A; PHASE-2 TRIAL; VIROLOGICAL RESPONSE; INTERFERON ALPHA-2A; HIV COINFECTION; TRIPLE THERAPY AB Background and aim Hepatitis C virus (HCV) treatment in patients coinfected with HIV has historically been limited by poor efficacy and medication toxicities. Direct-acting antivirals (e.g. boceprevir and telaprevir) improve treatment results in clinical trials, but little is known about the outcomes in community-based coinfected populations. This project aimed to describe the real-world effectiveness of boceprevir-based or telaprevir-based therapies in HIV/HCV coinfected patients. Materials and methods We identified HIV/HCV coinfected patients of all genotypes in the Veterans Affairs healthcare system who initiated pegylated interferon and ribavirin with or without boceprevir or telaprevir from June 2011 to November 2012 (n = 134). Results Sustained virologic response (SVR) was higher in genotype 1 patients receiving boceprevir or telaprevir [ n = 62, SVR = 50.0%, 95% confidence interval (CI) 37-63] versus pegylated interferon/ribavirin alone (n = 48, SVR = 33.3%, 95% CI 20-47). Patients with genotypes 2/3 treated with pegylated interferon/ribavirin (n = 24) achieved an SVR of 41.7% (95% CI 20-63). Only a few patients (15-25%) of each genotype completed more than 44 of 48 projected weeks. Treatment with boceprevir or telaprevir was the only characteristic independently associated with SVR in genotype 1 (adjusted odds ratio 2.2, 95% CI 1.1-4.7). Conclusion Addition of boceprevir or telaprevir to pegylated interferon/ribavirin improves treatment response in genotype 1 HIV/HCV coinfected patients. Treatment response is similar to reports from HCV monoinfected Veterans Affairs patients but lower than those reported in clinical trials. Early treatment discontinuation was common. (C) 2015 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Beste, Lauren A.] Vet Affairs Puget Sound Hlth Care Syst, Primary Care Serv, Seattle, WA 98108 USA. [Beste, Lauren A.; Green, Pamela K.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Beste, Lauren A.] Univ Washington, Dept Internal Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Ioannou, George N.] Univ Washington, Dept Internal Med, Div Gastroenterol, Seattle, WA 98195 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol Sect, Seattle, WA 98108 USA. RP Beste, LA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-111-GI, Seattle, WA 98108 USA. EM lauren.beste@va.gov FU VA Puget Sound Health Care System (Seattle, Washington); Clinical Science Research and Development, Office of Research and Development, Veterans Affairs [I01CX000320] FX This material is the result of work supported by resources from the VA Puget Sound Health Care System (Seattle, Washington). The study was funded by a Merit Review grant (I01CX000320), Clinical Science Research and Development, Office of Research and Development, Veterans Affairs (GNI). NR 23 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 0954-691X EI 1473-5687 J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD FEB PY 2015 VL 27 IS 2 BP 123 EP 129 DI 10.1097/MEG.0000000000000241 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AX9UZ UT WOS:000347248700002 PM 25503739 ER PT J AU Rosendorff, C AF Rosendorff, Clive TI Diuretics and potassium SO JOURNAL OF HYPERTENSION LA English DT Letter C1 [Rosendorff, Clive] Icahn Sch Med Mt Sinai, Mt Sinai Heart, Bronx, NY USA. [Rosendorff, Clive] Icahn Sch Med Mt Sinai, Dept Med, Bronx, NY USA. [Rosendorff, Clive] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@va.gov NR 4 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0263-6352 EI 1473-5598 J9 J HYPERTENS JI J. Hypertens. PD FEB PY 2015 VL 33 IS 2 BP 421 EP 422 DI 10.1097/HJH.0000000000000457 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AY2CM UT WOS:000347396100030 PM 25535881 ER PT J AU Wang, P Duan, D Zhou, X Li, X Yang, J Deng, M Xu, Y AF Wang, P. Duan, D. Zhou, X. Li, X. Yang, J. Deng, M. Xu, Y. TI Relationship between expression of human gingival beta-defensins and levels of periodontopathogens in subgingival plaque SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE antimicrobial cationic peptides; bacteria; beta-defensins; dental plaque; periodontitis ID POLYMERASE-CHAIN-REACTION; DENTICOLA SUPPRESSES EXPRESSION; ORAL EPITHELIAL-CELLS; REAL-TIME PCR; HUMAN BETA-DEFENSIN-1; PORPHYROMONAS-GINGIVALIS; ANTIMICROBIAL PEPTIDES; GENE-EXPRESSION; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; FUSOBACTERIUM-NUCLEATUM AB Background and ObjectiveHuman beta-defensins (hBDs) are a group of antimicrobial peptides important in epithelial innate immunity, and their differential expression is associated with periodontal diseases. The aim of this study was to explore relationships among hBDs, total subgingival bacteria and periodontopathogens in healthy subjects and in patients with chronic periodontitis. Material and MethodsThe periodontal clinical parameters of 29 healthy subjects and 25 patients with chronic periodontitis were recorded. The relative expression of hBD1, hBD2 and hBD3 genes in gingival biopsies was measured using real-time PCR. The numbers of total bacteria and of Treponema denticola, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Tannerella forsythia in subgingival plaque were quantified by real-time PCR. Data were analyzed using the Mann-Whitney U-test and Spearman's rank correlation test. ResultsNo significant differences in expression of the hBD genes were found between the group of healthy subjects and the group of patients with chronic periodontitis. Total bacteria and T.denticola were detected in all participants. F.nucleatum and T.forsythia were detected in all patients with chronic periodontitis and in 86.21% and 51.72%, respectively, of healthy volunteers. P.gingivalis and A.actinomycetemcomitans were detected in 24.14% and 17.24%, respectively, of the healthy group and in 84.00% and 12.00%, respectively, of the chronic periodontitis group. The prevalence of all bacteria, except A.actinomycetemcomitans, was significantly higher in the group of patients with chronic periodontitis than in the group of healthy subjects (p<0.05). A significant, negative correlation was observed between total bacteria and hBD-2 (r=-0.384, p=0.011). Upon analyzing the data in different groups, total bacteria and hBD-2 were significantly correlated (r=-0.492, p=0.026) only in the group of healthy subjects. ConclusionThe negative correlations between hBD-2 and total bacteria, especially in the group of healthy subjects, indicate that hBDs may play an important role by limiting an increase of bacterial load at the initial stage of periodontitis. C1 [Wang, P.; Duan, D.; Zhou, X.; Li, X.; Yang, J.; Xu, Y.] State Key Lab Oral Dis, Chengdu, Peoples R China. [Wang, P.] Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, Cambridge, MA USA. [Deng, M.] Univ N Carolina, Sch Dent, Oral Biol Program, Chapel Hill, NC USA. [Xu, Y.] Sichuan Univ, Dept Periodontol, West China Sch Stomatol, Chengdu SICHUAN UNI, Peoples R China. RP Xu, Y (reprint author), Sichuan Univ, Dept Periodontol, West China Sch Stomatol, 14,Sect 3,Renmin Nan Rd, Chengdu SICHUAN UNI, Peoples R China. EM schuehih@sohu.com OI deng, meng/0000-0002-9051-7534 FU Science and Technology Department of Sichuan Province [2011FZ0044]; National Science Foundation of China [30872872] FX The authors thank Dr Bo Han, Dr Ming Xuan, Dr YunLong Wu and Dr Jun Wu at the Department of Oral Surgery, West China School of Stomatology, Sichuan University for collecting the gingival tissues. The authors thank Dr Xiaoshan Wang (Epidemiology and Biostatistics Core, The Forsyth Institute) for his statistical assistance. This study was financially supported by the Foundation 2011FZ0044 from Science and Technology Department of Sichuan Province and National Science Foundation of China (30872872). NR 56 TC 2 Z9 3 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3484 EI 1600-0765 J9 J PERIODONTAL RES JI J. Periodont. Res. PD FEB PY 2015 VL 50 IS 1 BP 113 EP 122 DI 10.1111/jre.12187 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AY3EO UT WOS:000347467600013 PM 24814979 ER PT J AU Garnett, BR Masyn, KE Austin, SB Williams, DR Viswanath, K AF Garnett, Bernice R. Masyn, Katherine E. Austin, S. Bryn Williams, David R. Viswanath, Kasisomayajula TI Coping Styles of Adolescents Experiencing Multiple Forms of Discrimination and Bullying: Evidence From a Sample of Ethnically Diverse Urban Youth SO JOURNAL OF SCHOOL HEALTH LA English DT Article DE discrimination; bullying; coping style; latent class analysis; adolescents ID AFRICAN-AMERICAN ADOLESCENTS; RACIAL-DISCRIMINATION; DEPRESSION; VICTIMIZATION; MASSACHUSETTS; ATTRIBUTIONS; PREVALENCE; ADJUSTMENT; BEHAVIORS; SYMPTOMS AB BACKGROUNDWe used a latent class analysis (LCA) to characterize coping styles of urban youth and examined if coping styles moderated the association between experiencing discrimination and bullying and depressive symptoms. METHODSThe data come from the 2006 Boston Youth Survey, where students were asked to select 2 behaviors they do most often when they are upset, from a list of 15 options. A total of 927 (75%) students contributed to the LCA analytic sample (44% non-Hispanic Blacks, 29% Hispanics, and 58% girls). Relative and absolute fit indices determined the number of classes. An interaction term between types of discrimination and bullying experienced and coping style tested for moderation. RESULTSThe LCA revealed that a 3-class solution had the best fit (Lo-Mendell-Rubin likelihood ratio test, 4-class vs 3-class, p-value .12). The largest coping style class was characterized by high endorsement of distractive coping strategies (59%), the second class was characterized by using supportive coping strategies (27%), and the third class was characterized by using avoidance coping strategies (12%). We found a significant interaction between discrimination and coping style for depressive symptoms. CONCLUSIONSThe relationship between experiencing discrimination and depression varied based on coping style and the type of discrimination and bullying experienced. C1 [Garnett, Bernice R.] Univ Vermont, Coll Educ & Social Serv, Burlington, VT 05405 USA. [Masyn, Katherine E.] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. [Austin, S. Bryn; Williams, David R.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Austin, S. Bryn] Boston Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Hlth Commun Core,Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA. RP Garnett, BR (reprint author), Univ Vermont, Coll Educ & Social Serv, 533 Waterman Bldg,85 South Prospect St, Burlington, VT 05405 USA. EM bgarnett@uvm.edu; katherine_masyn@gse.harvard.edu; bryn.austin@childrens.harvard.edu; dwilliam@hsph.harvard.edu; Vish_Viswanath@dfci.harvard.edu NR 40 TC 2 Z9 2 U1 2 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4391 EI 1746-1561 J9 J SCHOOL HEALTH JI J. Sch. Health PD FEB PY 2015 VL 85 IS 2 BP 109 EP 117 DI 10.1111/josh.12225 PG 9 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY4II UT WOS:000347541000005 PM 25564979 ER PT J AU Foster, DW Langdon, KJ Schmidt, NB Zvolensky, M AF Foster, Dawn W. Langdon, Kirsten J. Schmidt, Norman B. Zvolensky, Michael TI Smoking Processes, Panic, and Depressive Symptoms Among Treatment-Seeking Smokers SO SUBSTANCE USE & MISUSE LA English DT Article DE Smoking; anxiety; panic; depression; cigarettes; tobacco; motives ID ANXIETY SENSITIVITY; CESSATION TREATMENT; CIGARETTE-SMOKING; PSYCHIATRIC-DISORDERS; OUTCOME EXPECTANCIES; ATTACK HISTORY; MOTIVES; DEPENDENCE; NICOTINE; PATTERNS AB Objectives: The present study evaluated the relative contribution of panic and depressive symptoms in relation to past cessation difficulties and smoking motives among treatment-seeking daily smokers. Methods: The sample included 392 treatment-seeking daily smokers (47.07% female; M-age = 35.48; SD = 13.56), who reported smoking an average of 10 or more cigarettes daily for at least one year. Results: Findings indicated that panic and depressive symptoms were significantly associated with quit problems as well as addictive and negative affect motives for smoking. However, depressive symptoms were not associated with habitual smoking motives. Conclusions: Differential patterns of associations with smoking-based processes imply that although panic and depression are related, there are important distinctions. Such data highlight the need for additional research to examine the putative role of panic and depressive symptoms in relation to smoking behaviors to further elucidate the mechanisms through which panic, depression, and smoking impact one another. C1 [Foster, Dawn W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA. [Langdon, Kirsten J.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Langdon, Kirsten J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Schmidt, Norman B.] Florida State Univ, Dept Psychol, Anxiety & Behav Hlth Clin, Tallahassee, FL 32306 USA. [Zvolensky, Michael] Univ Houston, Dept Psychol, Houston, TX USA. RP Foster, DW (reprint author), Yale Univ, Sch Med, Dept Psychiat, 34 Pk St, New Haven, CT 06519 USA. EM dawn.foster@yale.edu FU National Institute of Mental Health [R01 MH076629-01]; National Institute on Drug Abuse [K12-DA-000167] FX This project was supported by National Institute of Mental Health grant R01 MH076629-01 (Drs. Zvolensky and Schmidt). Additionally, preparation of this manuscript was supported in part by National Institute on Drug Abuse grant K12-DA-000167 (Dr. Foster). NIMH and NIDA had no direct role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. The contents of this manuscript do not necessarily represent the policy of the NIMH or NIDA, and as such, endorsement by the Federal Government should not be assumed. NR 40 TC 0 Z9 0 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PD FEB PY 2015 VL 50 IS 3 BP 394 EP 402 DI 10.3109/10826084.2014.984849 PG 9 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA AY0YR UT WOS:000347321100014 PM 25496170 ER PT J AU Pond, GR Bellmunt, J Rosenberg, JE Bajorin, DF Regazzi, AM Choueiri, TK Qu, AQ Niegisch, G Albers, P Necchi, A Di Lorenzo, G Fougeray, R Wong, YN Sridhar, SS Ko, YJ Milowsky, MI Galsky, MD Sonpavde, G AF Pond, G. R. Bellmunt, J. Rosenberg, J. E. Bajorin, D. F. Regazzi, A. M. Choueiri, T. K. Qu, A. Q. Niegisch, G. Albers, P. Necchi, A. Di Lorenzo, G. Fougeray, R. Wong, Y. -N. Sridhar, S. S. Ko, Y. -J. Milowsky, M. I. Galsky, M. D. Sonpavde, G. TI Impact of the Number of Prior Lines of Therapy and Prior Perioperative Chemotherapy in Patients Receiving Salvage Therapy for Advanced Urothelial Carcinoma: Implications for Trial Design SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Advanced; Number of prior regimens; Prior perioperative chemotherapy; Prognosis; Salvage therapy; Urothelial carcinoma ID TRANSITIONAL-CELL CARCINOMA; METASTATIC BREAST-CANCER; RANDOMIZED PHASE-III; OPEN-LABEL; INTERNAL VALIDATION; COLORECTAL-CANCER; 2ND-LINE THERAPY; SOLID TUMORS; SINGLE GROUP; DOUBLE-BLIND AB This analysis of patients from prospective trials of salvage therapy for advanced urothelial carcinoma did not identify a prognostic effect for number of prior lines of therapy and prior perioperative chemotherapy. Performance status, hemoglobin, liver metastasis, and time from prior chemotherapy were prognostic for outcomes. These findings allow trials to use uniform eligibility criteria, which will enhance accrual and improve interpretability. Background: The differential impact of the number of prior lines of therapy and the setting of prior therapy (perioperative or metastatic) is unclear in advanced urothelial carcinoma. Patients and Methods: Ten phase II trials of salvage chemotherapy, biologic agent therapy, or both, enrolling 731 patients, were available. Data on the number of prior lines of therapy and the setting of prior therapy were required in addition to known previously recognized prognostic factors: time from prior chemotherapy, hemoglobin level, performance status, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of the number of prior lines and prior perioperative therapy with overall survival (OS) as the primary clinical endpoint. Trial was a stratification factor. Results: A total of 711 patients were evaluable. The overall median progression-free survival and OS were 2.7 and 6.8 months, respectively. The number of prior lines was 1 in 559 patients (78.6%), 2 in 111 (15.6%), 3 in 29 (4.1%), 4 in 10 (1.4%), and 5 in 2 (0.3%). Prior perioperative chemotherapy was given to 277 (39.1%) and chemotherapy for metastatic disease to 454 (64.1%). The number of prior lines was not independently associated with OS (hazard ratio, 0.99; 95% CI, 0.86-1.14). Prior perioperative chemotherapy was a favorable factor for OS on univariate but not multivariate analysis. Conclusion: The number of prior lines of therapy and prior perioperative chemotherapy were not independently prognostic in patients with urothelial carcinoma receiving salvage therapy. Adoption of these data in salvage therapy trials should enhance accrual, the interpretability of results, and drug development. C1 [Pond, G. R.] McMaster Univ, Hamilton, NY USA. [Bellmunt, J.] Univ Hosp del Mar, Inst Hosp del Mar Invest Med, Barcelona, Spain. [Rosenberg, J. E.; Bajorin, D. F.; Regazzi, A. M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Choueiri, T. K.; Qu, A. Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, T. K.; Qu, A. Q.] Harvard Univ, Sch Med, Boston, MA USA. [Niegisch, G.; Albers, P.] Univ Dusseldorf, Dusseldorf, Germany. [Necchi, A.] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Di Lorenzo, G.] Univ Naples Federico II, Naples, Italy. [Fougeray, R.] Inst Rech Pierre Fabre, Boulogne, France. [Wong, Y. -N.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Sridhar, S. S.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Ko, Y. -J.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Milowsky, M. I.] Univ N Carolina, Chapel Hill, NC USA. [Galsky, M. D.] Mt Sinai Sch Med, Tisch Canc Ctr Inst, New York, NY USA. [Sonpavde, G.] Univ Alabama Birmingham, Ctr Comprehens Canc, 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 OI Regazzi, Ashley/0000-0002-6019-1852; Niegisch, Gunter/0000-0001-6929-8691; Rosenberg, Jonathan/0000-0003-2637-4249; Necchi, Andrea/0000-0002-3007-2756 NR 28 TC 5 Z9 5 U1 1 U2 6 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD FEB PY 2015 VL 13 IS 1 BP 71 EP 79 DI 10.1016/j.clgc.2014.06.004 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AY2HR UT WOS:000347410100018 PM 24993933 ER PT J AU Parekh, A Chen, MH Graham, P Mahal, BA Hirsch, AE Nakabayashi, M Evan, C Kantoff, PW Martin, NE Nguyen, PL AF Parekh, Arti Chen, Ming-Hui Graham, Powell Mahal, Brandon A. Hirsch, Ariel E. Nakabayashi, Mari Evan, Carolyn Kantoff, Philip W. Martin, Neil E. Nguyen, Paul L. TI Role of Androgen Deprivation Therapy in Early Salvage Radiation Among Patients With Prostate-Specific Antigen Level of 0.5 or Less SO CLINICAL GENITOURINARY CANCER LA English DT Article DE ADT; Prostate cancer; Salvage therapy; Surgical margins; Ultrasensitive PSA ID RADICAL PROSTATECTOMY; CANCER; RADIOTHERAPY; RECURRENCE; MEN AB In this study, we examine the benefit of adding androgen deprivation therapy (ADT) to salvage radiotherapy in modern patients followed with ultrasensitive prostate-specific antigen (PSA). In these 108 patients who received radical prostatectomy and salvage radiation at a PSA of 0.5 or less, we found that ADT was associated with a decreased risk of recurrence. This benefit appeared limited to men with negative margins, which suggests that men with positive margins and PSA <= 0.5 may be good candidates for salvage radiation alone. Background: The Radiation Therapy Oncology Group 96-01 randomized trial demonstrated the benefit of adding androgen deprivation therapy (ADT) to salvage radiotherapy for an increasing prostate-specific antigen (PSA) after prostatectomy, but it is unknown whether modern patients followed with ultrasensitive PSA and salvaged at a low PSA (ie, <= 0.5) also benefit from ADT. Patients and Methods: The cohort comprised 108 patients who received radical prostatectomy (RP), were followed by ultrasensitive PSA, and received salvage radiotherapy at a PSA of 0.5 or less. Sixty patients had negative margins, and 48 patients had positive margins at RP. Cox multivariable regression analysis was performed to identify factors associated with time to secondary PSA failure and included PSA at salvage, year of treatment, Gleason score, ADT use, margin status, T stage, and PSA doubling time. Occurrence of distant metastases was documented. Results: Median follow-up after radiation was 63.09 months. A total of 24 patients had a distant metastasis. In all patients, ADT use was associated with a decreased risk of recurrence (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.25-0.79; P = .006). On subgroup analysis, ADT was associated with a decreased risk of failure among patients with negative margins (HR, 0.27; 95% CI, 0.12-0.61; P = .002), but not among men with positive margins (HR, 0.78; 95% CI, 0.29-2.10; P = .63). Conclusions: Even patients followed with ultrasensitive PSA and salvaged early with a PSA <= 0.5 seem to benefit from the addition of ADT to salvage radiation. However, this benefit seemed to be limited to men with negative margins; thus, men with positive margins and PSA <= 0.5 may be good candidates for salvage radiation alone. C1 [Parekh, Arti; Graham, Powell; Mahal, Brandon A.; Martin, Neil E.; Nguyen, Paul L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02215 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT USA. [Hirsch, Ariel E.] Boston Univ, Sch Med, Boston Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. [Nakabayashi, Mari; Evan, Carolyn; Kantoff, Philip W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02215 USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02215 USA. EM pnguyen@LROC.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical Schoo; Fitz's Cancer Warriors; Prostate Cancer Foundation FX This work was supported by the Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School, Fitz's Cancer Warriors, Hugh Simons in Honor of Frank and Anne Simons, David and Cynthia Chapin, The Prostate Cancer Foundation, and a grant from an anonymous family foundation. NR 12 TC 1 Z9 1 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD FEB PY 2015 VL 13 IS 1 BP E1 EP E6 DI 10.1016/j.clgc.2014.06.0161 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AY2HR UT WOS:000347410100001 PM 25103271 ER PT J AU Lee, RJ Cohen, NA AF Lee, Robert J. Cohen, Noam A. TI Role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE acyl-homoserine lactone; bacterial infection; host-pathogen interactions; interkingdom signaling; nitric oxide ID SOLITARY CHEMOSENSORY CELLS; QUORUM-SENSING MOLECULES; NITRIC-OXIDE; PSEUDOMONAS-AERUGINOSA; BRUSH CELLS; ANTIMICROBIAL ACTIVITY; CYSTIC-FIBROSIS; AIRWAY; PERCEPTION; EXPRESSION AB Purpose of review Taste receptor family 2 (T2R) bitter taste receptors were originally identified and named on the basis of their role in type 2 taste cells of the tongue, in which they serve to detect the presence of potentially harmful ingested chemicals. In 2009, researchers demonstrated that airway epithelial cells also express T2R receptors, but their role in airway physiology and human disease has only recently begun to be identified. Recent findings Recent research has demonstrated that at least one airway T2R receptor, taste receptor family 2 isoform 38 protein (T2R38) is activated by secreted bacterial products. Activation of T2R38 in sinonasal epithelial cells stimulates nitric oxide production, increasing ciliary beating and directly killing bacteria. Clinical studies have also found correlations of TAS2R38 genotype with susceptibility to gram-negative upper respiratory infection and established T2R38 as an independent risk factor for chronic rhinosinusitis requiring sinus surgery. Summary These recent studies identify a role for T2R38 in sinonasal innate immunity and chronic rhinosinusitis. Clinical implications include the potential development of T2R38-directed topical therapies, as well as using taste testing and/or genotyping to predict susceptibility to infection. Further studies are needed to more clearly determine how TAS2R38 genotype affects patient outcomes in chronic rhinosinusitis and other upper airway diseases. C1 [Lee, Robert J.; Cohen, Noam A.] Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Div Rhinol, Hosp Univ Penn Ravdin Bldg,5th Floor,3400 Spruce, Philadelphia, PA 19104 USA. EM noam.cohen@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932; Lee, Robert/0000-0001-5826-6686 FU Flight Attendants Medical Research Institute [082478] FX Some of the research described here was supported by a grant from the Flight Attendants Medical Research Institute (082478) and a philanthropic contribution from the RLG Foundation, Inc., both to N.A.C. NR 77 TC 13 Z9 14 U1 7 U2 32 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-4050 EI 1473-6322 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD FEB PY 2015 VL 15 IS 1 BP 14 EP 20 DI 10.1097/ACI.0000000000000120 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA AX9ZX UT WOS:000347258500002 PM 25304231 ER PT J AU Levitsky, LL AF Levitsky, Lynne L. TI Disorders of growth and development: new genetics, new endocrinology, and new environmental challenges SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Editorial Material C1 [Levitsky, Lynne L.] Massachusetts Gen Hosp, Dept Pediat, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Levitsky, LL (reprint author), Harvard Univ, Sch Med, 175 Cambridge St, Boston, MA 02114 USA. EM LLevitsky@mgh.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2015 VL 22 IS 1 BP 34 EP 34 DI 10.1097/MED.0000000000000129 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX6IW UT WOS:000347027000007 PM 25546636 ER PT J AU Levitsky, LL Luria, AHO Hayes, FJ Lin, AE AF Levitsky, Lynne L. Luria, Anne H. O'Donnell Hayes, Frances J. Lin, Angela E. TI Turner syndrome: update on biology and management across the life span SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE aortic dissection; estrogen therapy; recombinant growth hormone therapy; short stature; Turner syndrome ID IDIOPATHIC SHORT STATURE; MULLERIAN HORMONE-LEVELS; BICUSPID AORTIC-VALVE; X-CHROMOSOME; PUBERTAL DEVELOPMENT; MAGNETIC-RESONANCE; MATERNAL PLASMA; CLINICAL-TRIAL; GH DEFICIENCY; SELF-ESTEEM AB Purpose of reviewWe review recent understanding of the pathophysiology, molecular biology, and management of Turner syndrome.Recent findingsSophisticated genetic techniques are able to detect mosaicism in one-third of individuals previously thought to have monosomy X. Prenatal detection using maternal blood should permit noninvasive detection of most fetuses with an X chromosome abnormality. Disproportionate growth with short limbs has been documented in this condition, and a target gene of short stature homeobox, connective tissue growth factor (Ctgf), has been described. Liver disease is more common in Turner syndrome than previously recognized. Most girls have gonadal failure. Spontaneous puberty and menarche is more commonly seen in girls with XX mosaicism. Low-dose estrogen replacement therapy may be given early to induce a more normal onset and tempo of puberty. Oocyte donation for assisted reproduction carries a substantial risk, particularly if the woman has known cardiac or aortic disease. Neurodevelopmental differences in Turner syndrome are beginning to be correlated with differences in brain anatomy.SummaryAn increased understanding of the molecular basis for aspects of this disorder is now developing. In addition, a renewed focus on health maintenance through the life span should provide better general and targeted healthcare for these girls and women. C1 [Levitsky, Lynne L.] Massachusetts Gen Hosp, Dept Pediat, Pediatr Endocrine Unit, Boston, MA 02114 USA. [Luria, Anne H. O'Donnell] Harvard Univ, Sch Med, Genet Residency Program, Boston, MA 02114 USA. [Luria, Anne H. O'Donnell; Lin, Angela E.] Boston Childrens Hosp, Boston, MA USA. [Hayes, Frances J.] Massachusetts Gen Hosp, Dept Med, Reproduct Endocrine Unit, Boston, MA 02114 USA. Mass Gen Hosp Children, Gegenet Unit, Boston, MA 02114 USA. RP Levitsky, LL (reprint author), Harvard Univ, Sch Med, 175 Cambridge St, Boston, MA 02114 USA. EM LLevitsky@mgh.harvard.edu OI O'Donnell-Luria, Anne/0000-0001-6418-9592 NR 90 TC 4 Z9 4 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2015 VL 22 IS 1 BP 65 EP 72 DI 10.1097/MED.0000000000000128 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX6IW UT WOS:000347027000012 PM 25517026 ER PT J AU Lambertini, M Ginsburg, ES Partridge, AH AF Lambertini, Matteo Ginsburg, Elizabeth S. Partridge, Ann H. TI Update on fertility preservation in young women undergoing breast cancer and ovarian cancer therapy SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Review DE BRCA1 and BRCA2 mutations; breast cancer; fertility issues; ovarian cancer; young women ID PREIMPLANTATION GENETIC DIAGNOSIS; IN-VITRO FERTILIZATION; HORMONE AGONISTS; CONSERVATIVE MANAGEMENT; SPARING SURGERY; PREMENOPAUSAL WOMEN; AMERICAN-SOCIETY; RANDOMIZED-TRIAL; MATURED OOCYTES; BRCA2 MUTATION AB Purpose of review The purpose of the article is to review the available options for fertility preservation in patients with breast and ovarian cancer, and the special issues faced by BRCA mutation carriers. Recent findings Future fertility is an important consideration for many young patients with cancer. There are both experimental and standard available strategies for patients with breast and ovarian cancer to preserve fertility, and each has potential advantages and disadvantages. Summary Embryo cryopreservation is widely available with a highly successful track record. Improvements in laboratory techniques have led to oocyte cryopreservation recently being recategorized as nonexperimental. Conservative gynecologic surgery is a standard consideration for patients with stage I ovarian cancer who desire future fertility. Ovarian tissue cryopreservation as well as ovarian suppression with luteinizing hormone-releasing hormone analogs during chemotherapy are considered experimental methods at this time, although recent data suggest both safety and efficacy for the use of luteinizing hormone-releasing hormone analogs in women receiving (neo)adjuvant chemotherapy for breast cancer. Special issues should be considered for women with BRCA mutations because of the need to undergo preventive surgery at young age. Multidisciplinary teams and well functioning relationships between the oncology and reproductive units are crucial to manage the fertility issues of young women with cancer. C1 [Lambertini, Matteo; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lambertini, Matteo] IRCCS AOU San Martino IST, Dept Med Oncol, UO Oncol Med 2, Genoa, Italy. [Ginsburg, Elizabeth S.] Brigham & Womens Hosp, Ctr Infertil & Reprod Surg, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Ann_Partridge@dfci.harvard.edu OI Lambertini, Matteo/0000-0003-1797-5296 NR 93 TC 14 Z9 14 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-872X EI 1473-656X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD FEB PY 2015 VL 27 IS 1 BP 98 EP 107 DI 10.1097/GCO.0000000000000138 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AX9WZ UT WOS:000347251200016 PM 25490381 ER PT J AU Basch, E Autio, KA Smith, MR Bennett, AV Weitzman, AL Scheffold, C Sweeney, C Rathkopf, DE Smith, DC George, DJ Higano, CS Harzstark, AL Sartor, AO Gordon, MS Vogelzang, NJ de Bono, JS Haas, NB Corn, PG Schimmoller, F Scher, HI AF Basch, Ethan Autio, Karen A. Smith, Matthew R. Bennett, Antonia V. Weitzman, Aaron L. Scheffold, Christian Sweeney, Christopher Rathkopf, Dana E. Smith, David C. George, Daniel J. Higano, Celestia S. Harzstark, Andrea L. Sartor, A. Oliver Gordon, Michael S. Vogelzang, Nicholas J. de Bono, Johann S. Haas, Naomi B. Corn, Paul G. Schimmoller, Frauke Scher, Howard I. TI Effects of Cabozantinib on Pain and Narcotic Use in Patients with Castration-resistant Prostate Cancer: Results from a Phase 2 Nonrandomized Expansion Cohort SO EUROPEAN UROLOGY LA English DT Article DE mCRPC; Pain control; Patient-reported outcomes; Phase 2 trial; Quality of life; Tyrosine kinase inhibitor ID MITOXANTRONE PLUS PREDNISONE; REPORTED OUTCOMES; CLINICAL-TRIALS; RANDOMIZED-TRIAL; END-POINTS; RECOMMENDATIONS; CHEMOTHERAPY; MET; METASTASIS; INHIBITOR AB Background: Pain negatively affects quality of life for cancer patients. Preliminary data in metastatic castration-resistant prostate cancer (mCRPC) suggested a benefit of the oral tyrosine kinase inhibitor cabozantinib to pain palliation. Objective: Prospective evaluation of cabozantinib's benefits on pain and narcotic use in mCRPC. Design, setting, and participants: This was a nonrandomized expansion (NRE) cohort (n = 144) of a phase 2 randomized discontinuation trial in docetaxel-refractory mCRPC patients. Pain and interference of symptoms with sleep and general activity were electronically self-reported daily for 7-d intervals at baseline and regularly scheduled throughout the study. Mean per-patient scores were calculated for each interval. Narcotic use was recorded daily during the same intervals. Intervention: Open-label cabozantinib (100 mg or 40 mg). Outcome measurements and statistical analysis: The following stringent response definition was used: clinically meaningful pain reduction (>= 30% improvement in mean scores from baseline) confirmed at a later interval without concomitant increases in narcotics. Only patients with moderate or severe baseline pain were analyzed. Results and limitations: Sixty-five patients with moderate or severe baseline pain were evaluable. Of these, 27 (42%) experienced pain palliation according to the stringent response definition. Thirty-seven patients (57%) had clinically meaningful pain relief at two consecutive intervals, reported >= 6 wk apart in the majority. Forty-four patients (68%) had palliation at one or more intervals; 36 (55%) decreased narcotics use during one or more intervals. Clinically meaningful pain reduction was associated with significant (p <= 0.001) improvements in sleep quality and general activity. A limitation of this study was its open-label design. Conclusions: Cabozantinib demonstrated clinically meaningful pain palliation, reduced or eliminated patients' narcotic use, and improved patient functioning, thus meriting prospective validation in phase 3 studies. Patient summary: We evaluated the potential of cabozantinib to improve symptoms in patients with metastatic prostate cancer that no longer responds to standard therapies. We saw a promising reduction in pain and reduced need for narcotic painkillers. Larger, well-controlled trials are necessary to confirm these findings. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Basch, Ethan; Bennett, Antonia V.] Univ N Carolina, Canc Outcomes Res Program, Lineberger Canc Ctr, Chapel Hill, NC 27599 USA. [Autio, Karen A.; Rathkopf, Dana E.; Scher, Howard I.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY 10021 USA. [Autio, Karen A.; Scher, Howard I.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Genitourinary Oncol Program, Boston, MA 02114 USA. [Weitzman, Aaron L.; Scheffold, Christian; Schimmoller, Frauke] Exelixis Inc, Clin Dev, San Francisco, CA USA. [Sweeney, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, David C.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [George, Daniel J.] Duke Univ, Med Ctr, Durham, NC USA. [Higano, Celestia S.] Univ Washington, Dept Med, Div Med Oncol, Seattle, WA 98195 USA. [Harzstark, Andrea L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sartor, A. Oliver] Tulane Univ, Tulane Canc Ctr, New Orleans, LA 70118 USA. [Gordon, Michael S.] Pinnacle Oncol Hematol, Scottsdale, AZ USA. [Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [de Bono, Johann S.] Royal Marsden Hosp, Drug Dev Unit, Sutton, Surrey, England. [Haas, Naomi B.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Corn, Paul G.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. RP Basch, E (reprint author), Univ N Carolina, Canc Outcomes Res Program, 170 Manning Dr CB 7305,Phys Off Bldg,Suite 3185, Chapel Hill, NC 27599 USA. EM Ebasch@med.unc.edu OI Rathkopf, Dana/0000-0002-4503-7582 FU Exelixis, Inc.; US Department of Defense (DOD) Prostate Cancer Clinical Trials Consortium at Memorial Sloan-Kettering Cancer Center; Prostate Cancer Foundation; National Cancer Institute; DOD [W81XWH-11-1-0639] FX This study was sponsored by Exelixis, Inc. Employees of the sponsor were involved in study design, collection of the data, management of the data, manuscript review, and manuscript writing. Additional funding was provided by the US Department of Defense (DOD) Prostate Cancer Clinical Trials Consortium at Memorial Sloan-Kettering Cancer Center and the Prostate Cancer Foundation. E. Basch's research is supported by grants from the National Cancer Institute and the DOD (grant W81XWH-11-1-0639); this work does not represent the views or opinions of the DOD. NR 34 TC 12 Z9 13 U1 5 U2 11 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 FEB PY 2015 VL 67 IS 2 BP 310 EP 318 DI 10.1016/j.eururo.2014.02.013 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AX6LJ UT WOS:000347033500038 PM 24631409 ER PT J AU Economopoulos, KP Stamou, A Sergentanis, TN AF Economopoulos, Konstantinos P. Stamou, Aliki Sergentanis, Theodoros N. TI Re: Luis Felipe Brandao, Riccardo Autorino, Humberto Laydner, et al. Robotic Versus Laparoscopic Adrenalectomy: A Systematic Review and Meta-analysis. Eur Urol 2014; 65: 1154-61 SO EUROPEAN UROLOGY LA English DT Letter C1 [Economopoulos, Konstantinos P.; Sergentanis, Theodoros N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Economopoulos, Konstantinos P.; Stamou, Aliki; Sergentanis, Theodoros N.] Soc Jr Doctors, Athens, Greece. [Sergentanis, Theodoros N.] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece. RP Economopoulos, KP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 101 Merrimack St, Boston, MA 02114 USA. EM keconomopoulos@mgh.harvard.edu OI Economopoulos, Konstantinos/0000-0003-4856-0405; Sergentanis, Theodoros N./0000-0002-9355-5528 NR 5 TC 1 Z9 1 U1 1 U2 4 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 FEB PY 2015 VL 67 IS 2 BP E32 EP E32 DI 10.1016/j.eururo.2014.09.052 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AX6LJ UT WOS:000347033500009 PM 25311953 ER PT J AU Coleman, CN Sullivan, JM Bader, JL Murrain-Hill, P Koerner, JF Garrett, AL Weinstock, DM Case, C Hrdina, C Adams, SA Whitcomb, RC Graeden, E Shankman, R Lant, T Maidment, BW Hatchett, RC AF Coleman, C. Norman Sullivan, Julie M. Bader, Judith L. Murrain-Hill, Paula Koerner, John F. Garrett, Andrew L. Weinstock, David M. Case, Cullen, Jr. Hrdina, Chad Adams, Steven A. Whitcomb, Robert C. Graeden, Ellie Shankman, Robert Lant, Timothy Maidment, Bert W. Hatchett, Richard C. TI PUBLIC HEALTH AND MEDICAL PREPAREDNESS FOR A NUCLEAR DETONATION: THE NUCLEAR INCIDENT MEDICAL ENTERPRISE SO HEALTH PHYSICS LA English DT Article DE National Council on Radiation Protection and Measurements; emergency planning; nuclear war; radiological terrorism ID SCARCE RESOURCES; RADIATION VICTIMS; GLOBAL CONSENSUS; DECISION-MODEL; MASS-CASUALTY; MANAGEMENT; EMERGENCIES; ALLOCATION; TRIAGE; TOOLS AB Resilience and the ability to mitigate the consequences of a nuclear incident are enhanced by (1) effective planning, preparation and training; (2) ongoing interaction, formal exercises, and evaluation among the sectors involved; (3) effective and timely response and communication; and (4) continuous improvements based on new science, technology, experience, and ideas. Public health and medical planning require a complex, multifaceted systematic approach involving federal, state, local, tribal, and territorial governments; private sector organizations; academia; industry; international partners; and individual experts and volunteers. The approach developed by the U.S. Department of Health and Human Services Nuclear Incident Medical Enterprise (NIME) is the result of efforts from government and nongovernment experts. It is a "bottom-up" systematic approach built on the available and emerging science that considers physical infrastructure damage, the spectrum of injuries, a scarce resources setting, the need for decision making in the face of a rapidly evolving situation with limited information early on, timely communication, and the need for tools and just-in-time information for responders who will likely be unfamiliar with radiation medicine and uncertain and overwhelmed in the face of the large number of casualties and the presence of radioactivity. The components of NIME can be used to support planning for, response to, and recovery from the effects of a nuclear incident. Recognizing that it is a continuous work-in-progress, the current status of the public health and medical preparedness and response for a nuclear incident is provided. C1 [Coleman, C. Norman; Sullivan, Julie M.; Bader, Judith L.; Murrain-Hill, Paula; Koerner, John F.; Garrett, Andrew L.; Shankman, Robert] Dept Hlth & Human Serv, Off Emergency Management, Off Assistant Secretary Preparedness & Response, Washington, DC USA. [Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Weinstock, David M.; Case, Cullen, Jr.] Natl Marrow Donor Program, Radiat Injury Treatment Network, Minneapolis, MN USA. [Hrdina, Chad] Dept Hlth & Human Serv, Off Policy & Planning, Off Assistant Secretary Preparedness & Response, Washington, DC USA. [Adams, Steven A.] Ctr Dis Control & Prevent, Div Strateg Natl Stockpile, Off Publ Hlth Preparedness & Response, Atlanta, GA USA. [Whitcomb, Robert C.] Ctr Dis Control & Prevent, Radiat Studies Branch, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA USA. [Graeden, Ellie] Gryphon Sci LLC, Rockville, MD USA. [Lant, Timothy; Hatchett, Richard C.] Dept Hlth & Human Serv, Biomed Adv Res & Dev Author, Off Assistant Secretary Preparedness & Response, Washington, DC USA. [Maidment, Bert W.] NIAID, Radiat Nucl Countermeasures Program, NIH, Bethesda, MD 20892 USA. RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM ccoleman@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 53 TC 9 Z9 9 U1 2 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2015 VL 108 IS 2 BP 149 EP 160 DI 10.1097/HP.0000000000000249 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA AX6YN UT WOS:000347064100011 PM 25551496 ER PT J AU Lee, J Jeon, JY Meyerhardt, JA AF Lee, Junga Jeon, Justin Y. Meyerhardt, Jeffrey A. TI Diet and Lifestyle in Survivors of Colorectal Cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Colorectal cancer; Cancer survival; Lifestyle factors; Epigenetics ID BODY-MASS INDEX; III COLON-CANCER; RECREATIONAL PHYSICAL-ACTIVITY; TREATMENT-RELATED TOXICITY; ADJUVANT CHEMOTHERAPY; RECTAL-CANCER; DIAGNOSIS; IMPACT; GROWTH; ASSOCIATION AB Much research supports the association between diet and lifestyle in the development of colorectal cancer. Recent studies have demonstrated an association between various energy balance host factors (obesity, physical inactivity, and certain dietary factors) and outcomes. This review summarizes the impact of modifiable lifestyle factors, including prediagnosis and postdiagnosis adiposity, physical activity, and diet, on the prognosis of patients with colorectal cancer. The article focuses on associations of these factors in survivors of stage I to III colorectal cancer, and summarizes the possible mechanisms for the association between modifiable lifestyle factors and the prognosis of patients with colorectal cancer. C1 [Lee, Junga; Jeon, Justin Y.] Yonsei Univ, Exercise Med Ctr Canc & Diabet Patients, Dept Sport & Leisure Studies, Seoul 120749, South Korea. [Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM jmeyerhardt@partners.org FU NCI NIH HHS [P50 CA127003, R01 CA149222, R01 CA169141, U54 CA155626] NR 53 TC 8 Z9 8 U1 6 U2 24 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 2015 VL 29 IS 1 BP 1 EP + DI 10.1016/j.hoc.2014.09.005 PG 28 WC Oncology; Hematology SC Oncology; Hematology GA AX5FD UT WOS:000346951300002 PM 25475570 ER PT J AU Chan, CHF Cusack, JC Ryan, DP AF Chan, Carlos H. F. Cusack, James C. Ryan, David P. TI A Critical Look at Local-Regional Management of Peritoneal Metastasis SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Colorectal cancer; Carcinomatosis; Cytoreductive surgery; Hyperthermic intraperitoneal chemotherapy; Systemic chemotherapy ID HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; COLORECTAL-CANCER; SYSTEMIC CHEMOTHERAPY; CYTOREDUCTIVE SURGERY; RANDOMIZED-TRIAL; CARCINOMATOSIS; ORIGIN; SURVIVAL AB For patients with stage IV colorectal cancer, the presence of peritoneal metastases is a poor prognostic feature. Despite the improvement in systemic therapy, long-term survival remains poor for patients with peritoneal carcinomatosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be associated with long-term survival in patients who have limited peritoneal disease, particularly those who can have complete cytoreduction. Whether the possible benefit of CRS and HIPEC is from the surgical resection of all disease or the combination of CRS and HIPEC remains unclear. C1 [Chan, Carlos H. F.; Cusack, James C.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA 02114 USA. [Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Div Med Oncol, Boston, MA 02114 USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Med Oncol, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM DPRYAN@mgh.harvard.edu NR 20 TC 4 Z9 4 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 2015 VL 29 IS 1 BP 153 EP + DI 10.1016/j.hoc.2014.09.006 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA AX5FD UT WOS:000346951300009 PM 25475577 ER PT J AU Denny, BT Fan, J Liu, X Ochsner, KN Guerreri, S Mayson, SJ Rimsky, L McMaster, A New, AS Goodman, M Siever, LJ Koenigsberg, HW AF Denny, Bryan T. Fan, Jin Liu, Xun Ochsner, Kevin N. Guerreri, Stephanie Mayson, Sarah Jo Rimsky, Liza McMaster, Antonia New, Antonia S. Goodman, Marianne Siever, Larry J. Koenigsberg, Harold W. TI Elevated amygdala activity during reappraisal anticipation predicts anxiety in avoidant personality disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Avoidant personality disorder; Reappraisal; Anticipation; Anxiety; FMRI; Amygdala ID GENERALIZED SOCIAL PHOBIA; COGNITIVE REAPPRAISAL; EMOTION REGULATION; BORDERLINE; PICTURES; BRAIN AB Background: Avoidant personality disorder is characterized by pervasive anxiety, fear of criticism, disapproval, and rejection, particularly in anticipation of exposure to social situations. An important but underexplorecl question concerns whether anxiety in avoidant patients is associated with an impaired ability to engage emotion regulatory strategies in anticipation of and during appraisal of negative social stimuli. Methods: We examined the use of an adaptive emotion regulation strategy, cognitive reappraisal, in avoidant patients. In addition to assessing individual differences in state and trait anxiety levels, self-reported affect as well as measures of neural activity were compared between 17 avoidant patients and 21 healthy control participants both in anticipation of and during performance of a reappraisal task. Results: Avoidant patients showed greater state and trait related anxiety relative to healthy participants. In addition, relative to healthy participants, avoidant patients showed pronounced amygdala hyper-reactivity during reappraisal anticipation, and this hyper reactivity effect was positively associated with increasing self reported anxiety levels. Limitations: Our finding of exaggerated amygdala activity during reappraisal anticipation could reflect anxiety about the impending need to reappraise, anxiety about the certainty of an upcoming negative image, or anxiety relating to anticipated scrutiny of task responses by the experimenters. While we believe that all of these possibilities are consistent with the phenomenology of avoidant personality disorder, future research may clarify this ambiguity. Conclusions: These results suggest that amygclala reactivity in anticipation of receiving negative social information may represent a key component of the neural mechanisms underlying the heightened anxiety present in avoidant patients. Published by Elsevier B.V. C1 [Denny, Bryan T.; Fan, Jin; Guerreri, Stephanie; Mayson, Sarah Jo; Rimsky, Liza; McMaster, Antonia; New, Antonia S.; Goodman, Marianne; Siever, Larry J.; Koenigsberg, Harold W.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Fan, Jin] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Fan, Jin] CUNY Queens Coll, Dept Psychol, New York, NY 11367 USA. [Liu, Xun] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. [Ochsner, Kevin N.] Columbia Univ, Dept Psychol, New York, NY 10027 USA. RP Koenigsberg, HW (reprint author), James J Peters VA Med Ctr, Mental Hlth Patient Care Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM HWarrenK@nyc.rr.com RI Fan, Jin/A-6716-2009 OI Fan, Jin/0000-0001-9630-8330 FU National Institute of Mental Health; James J Peters VA Medical Center; National Center for Advancing Translational Sciences (a component of the National Institutes of Health) FX This research was funded by the National Institute of Mental Health, the James J Peters VA Medical Center, and the National Center for Advancing Translational Sciences (a component of the National Institutes of Health). This publication is solely the work of the authors. The study sponsors had no role in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. NR 36 TC 3 Z9 3 U1 2 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB 1 PY 2015 VL 172 BP 1 EP 7 DI 10.1016/j.jad.2014.09.017 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AX0LD UT WOS:000346643000001 PM 25451388 ER PT J AU Blanc, J Bui, E Mouchenik, Y Derivois, D Birmes, P AF Blanc, Judite Bui, Eric Mouchenik, Yoram Derivois, Daniel Birmes, Philippe TI Prevalence of post-traumatic stress disorder and depression in two groups of children one year after the January 2010 earthquake in Haiti SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Depression; Children; Earthquake; Post-traumatic stress disorder ID SYMPTOMS; SURVIVORS; VICTIMS AB Background: More than 500 studies were conducted in Haiti following the January 12 of 2010 earthquake, yet few of them assessed mental health of the population. To our knowledge, none targeted the effectiveness of various methods used to treat survivors, whether adults or children Method: Our study aimed to assess one year after the disaster, the effect of a specific psycho-social support offered to relocated children in Port-au-Prince compared with a control group. Results: The two groups were homogeneous in the intensity of the peritraumatic distress they experienced. We were unable to show a significant difference between both in the average scores for PTSD, nor for depression, nor in three out of the four sub-scales of the Child Behavior Check-List. In case children, 68% and 40.9%, respectively, and 50% and 20.5% of the control group, reported severe levels of the symptoms of PTSD and depression. These surprising results can be explained by the absence of equivalence in the two groups from a socio-demographic point of view and because subjects were not randomly selected in the recruitment process. Conclusion: This study has not made it possible to indicate the effectiveness of a specific psycho-social support offered to children in the aftermath of the disaster. On the other hand, the sample illustrates the high prevalence (more than 50% for PTSD) of severe post-traumatic stress in this group of school-age children, one year after the earthquake. These results indicate that serious attention should be paid to the mental health aspects in reconstruction program for the country. (C) 2014 Elsevier B.V. All rights reserved, C1 [Blanc, Judite; Mouchenik, Yoram] Univ Paris 13, Lab UTRPP, F-93430 Villetaneuse, France. [Blanc, Judite] Univ Toulouse, Lab Stress Traumat, Toulouse, France. [Blanc, Judite] Univ Etat Haiti, FASCH, Port Au Prince, Haiti. [Bui, Eric] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders,RSF MGH Ho, Boston, MA 02114 USA. [Derivois, Daniel] Univ Lyon 2, Lab CRPPC, F-69365 Lyon 07, France. [Birmes, Philippe] Univ Hosp Toulouse, LST, EA 4560, Toulouse, France. [Birmes, Philippe] Univ Toulouse 3, F-31062 Toulouse, France. RP Blanc, J (reprint author), Univ Paris 13, Lab UTRPP, 99 Ave Jean Baptiste Clement, F-93430 Villetaneuse, France. EM juditeblanc@yahoo.fr RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 FU Agency Nationale de la Recherche in France FX The translation of the manuscript front french to english was made possible by ANR-10-HAIT-002 RECREAHVI project supported by Agency Nationale de la Recherche in France NR 25 TC 4 Z9 4 U1 3 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB 1 PY 2015 VL 172 BP 121 EP 126 DI 10.1016/j.jad.2014.09.055 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AX0LD UT WOS:000346643000018 PM 25451405 ER PT J AU Uchida, M Serra, G Zayas, L Kenworthy, T Hughes, B Koster, A Faraone, SV Biederman, J AF Uchida, Mai Serra, Giulia Zayas, Lazaro Kenworthy, Tara Hughes, Brittany Koster, Ariana Faraone, Stephen V. Biederman, Joseph TI Can manic switches be predicted in pediatric major depression? A systematic literature review SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE Bipolar disorder; Major depressive disorder; Manic switch; Pediatric ID BIPOLAR DISORDER; CLINICAL CHARACTERISTICS; CONDUCT DISORDER; FOLLOW-UP; ADHD YOUTH; ADOLESCENTS; CHILDREN; BEHAVIOR; PROFILE; YOUNG AB Background: The rate of switching from major depression to bipolar disorder is high in children. Predicting who is at risk for switching poses unique challenges and is of high clinical relevance. Our aim was to examine the existing scientific literature elucidating if certain clinical correlates predict ultimate bipolar switches in children initially presenting with a depressive episode. Methods: We conducted a systematic literature search of studies assessing the risk factors for bipolar switching in youth. In all, seven studies fit our a priori criteria and were thus included in our qualitative review. Results: Together, these papers found that manic switches in pediatric depression can be predicted by several risk factors, including positive family history of mood disorders, emotional and behavioral dysregulation, subthreshold mania, and psychosis. Limitations: We identified only seven prospective informative studies for our review. The majority of subjects included in these studies were referred and Caucasian. Thus, the results may not generalize to other community samples and other ethnicities. Conclusions: These findings can help alert clinicians of the risk of manic switches. (C) 2014 Elsevier B.V. All rights reserved. C1 [Uchida, Mai; Kenworthy, Tara; Hughes, Brittany; Koster, Ariana; Biederman, Joseph] Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. [Zayas, Lazaro] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Serra, Giulia] Univ Roma La Sapienza, NESMOS Dept, St Andrea Hosp, I-00185 Rome, Italy. [Uchida, Mai; Serra, Giulia; Zayas, Lazaro; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Uchida, M (reprint author), 55 Fruit St,Warren 625, Boston, MA 02114 USA. EM muchida@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Massachusetts General Hospital Pediatric Psychopharmacology Council Fund FX This work was supported in part by the Massachusetts General Hospital Pediatric Psychopharmacology Council Fund. The funding source had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. NR 39 TC 1 Z9 1 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB 1 PY 2015 VL 172 BP 300 EP 306 DI 10.1016/j.jad.2014.10.046 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AX0LD UT WOS:000346643000042 PM 25451429 ER PT J AU Pietrzak, RH Rosenheck, RA Cramer, JA Vessichio, JC Tsai, J Southwick, SM Krystal, JH AF Pietrzak, Robert H. Rosenheck, Robert A. Cramer, Joyce A. Vessichio, Jennifer C. Tsai, Jack Southwick, Steven M. Krystal, John H. CA VA CSP 504 Collaborative Grp TI Elucidating the transdiagnostic dimensional structure of trauma-related psychopathology: Findings from VA cooperative study 504-risperidone treatment for military service related chronic post traumatic stress disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Posttraumatic stress disorder; Depression; Generalized anxiety disorder; Veterans; Exploratory factor analysis; Functioning ID RESEARCH DOMAIN CRITERIA; 5-FACTOR MODEL; SYMPTOMS; VETERANS; ANXIETY; DEPRESSION; SCALE; PTSD; RDOC; DISTRESS AB Background: Three of the most common trauma-related mental disorders posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD) are highly comorbid and share common transdiagnostic symptom dimensions of threat (i.e., fear) and loss (i.e., dysphoria) symptomatology. However, empirical evaluation of the dimensional structure of component aspects of these disorders is lacking. Methods: Using structured clinical interview data from U.S. military veterans with chronic military related PTSD, we evaluated the transdiagnostic dimensional structure of PTSD, MDD, and GAD symptoms. We then examined the relationship between the best-fitting transdiagnostic model of these symptoms, and measures of physical and mental functioning, and life satisfaction and well-being. Results: Exploratory factor analysis revealed that a 3-factor transdiagnostic model comprised of loss (i.e., dysphoria), threat (i.e., anxious arousal, re-experiencing, and avoidance symptoms), and somatic anxiety (i.e., physiological manifestations of anxiety) symptoms provided the best representation of trauma related PTSD, MDD, and GAD symptoms. Somatic anxiety symptoms were independently associated with physical functioning, while loss symptoms were independently associated with mental functioning and life satisfaction and well-being. Limitations: Evaluation of study aims in a relatively homogeneous sample of veterans with chronic, military related PTSD. Conclusions: Results of this study suggest that a 3-factor transdiagnostic model best characterizes the dimensional structure of PTSD, MDD, and GAD symptoms in military veterans with chronic military-related PTSD. This model evidenced external validity in demonstrating differential associations with measures of physical and mental functioning, and life satisfaction and well-being. Results provide support for emerging contemporary models of psychopathology, which emphasize transdiagnostic and dimensional conceptualizations of mental disorders. Such models may have utility in understanding the Functional status of trauma survivors. Published by Elsevier B.V. C1 [Pietrzak, Robert H.; Southwick, Steven M.; Krystal, John H.] VA Connecticut Healthcare Syst, Clin Neurosci Div, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA. [Pietrzak, Robert H.; Rosenheck, Robert A.; Cramer, Joyce A.; Vessichio, Jennifer C.; Tsai, Jack; Southwick, Steven M.; Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06516 USA. [Rosenheck, Robert A.; Tsai, Jack; Krystal, John H.] New England Mental Illness Res Educ & Clin Ctr, US Dept Vet Affairs, West Haven, CT USA. [Cramer, Joyce A.; Vessichio, Jennifer C.] VA Connecticut Healthcare Syst, Psychiat Serv, West Haven, CT USA. [Krystal, John H.] Yale New Haven Med Ctr, Psychiat Serv, New Haven, CT 06504 USA. RP Pietrzak, RH (reprint author), Yale Univ, Sch Med, US Dept Vet Affairs,Dept Psychiat, Natl Ctr Posttraumat Stress Disorder,VA Connectic, 950 Campbell Ave,151E, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu FU U.S. Department of Veterans Affairs [504]; National Institute on Alcohol Abuse and Alcoholism [2P50AA012870-14] FX This study was supported by the U.S. Department of Veterans Affairs through its support of VA Cooperative Study #504, Clinical Neuroscience Division of the VA National Center for PTSD, and the Consortium to Alleviate PTSD. Johnson and Johnson provided medication and some financial support to the U.S. Department of Veterans Affairs to facilitate the initiation and conduct of the study. Additionally Dr. Krystal received support from the National Institute on Alcohol Abuse and Alcoholism grant (2P50AA012870-14) and the National Center for Advancing Translational Science grants (UL1RR024139, PI: R. Sherwin, UH2TR000960, PI: JHK). NR 30 TC 0 Z9 0 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB 1 PY 2015 VL 172 BP 331 EP 336 DI 10.1016/j.jad.2014.10.025 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AX0LD UT WOS:000346643000047 PM 25451434 ER PT J AU Jacobsen, KK Nievergelt, CM Zayats, T Greenwood, TA Anttila, V Akiskal, HS Haavik, J Fasmer, OB Kelsoe, JR Johansson, S Oedegaard, KJ AF Jacobsen, Kaya K. Nievergelt, Caroline M. Zayats, Tetyana Greenwood, Tiffany A. Anttila, Verneri Akiskal, Hagop S. Haavik, Jan Fasmer, Ole Bernt Kelsoe, John R. Johansson, Stefan Oedegaard, Ketil J. CA BiGs Consortium IHG Consortium TI Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar disorder; Migraine; Genetics; NBEA; Neurobeachin ID RECEPTOR TRAFFICKING; SUSCEPTIBILITY LOCI; GENETIC ASSOCIATION; NEUROBEACHIN; PREVALENCE; METAANALYSIS; POPULATION; GLUTAMATE; LINKAGE; AUTISM AB Background: Migraine is a common comorbidity among individuals with bipolar disorder, but the underlying mechanisms for this cooccurrence are poorly understood. The aim of this study was to investigate the genetic background of bipolar patients with and without migraine. Methods: We performed a genome-wide association analysis contrasting 460 bipolar migraneurs with 914 bipolar patients without migraine from the Bipolar Genome Study (BiGS). Results We identified one genome-wide significant association between migraine in bipolar disorder patients and rs1160720, an intronic single nucleotide polymorphism (SNP) in the NBEA gene (P=2.97 x 10(-8), OR: 1.82, 95% Cl: 1.47-225), although this was not replicated in a smaller sample of 289 migraine cases. Limitations: Our study is based on self reported migraine. Conclusions: NBEA encodes neurobeachin, a scaffolding protein primarily expressed in the brain and involved in trafficking of vesicles containing neurotransmitter receptors. This locus has not previously been implicated in migraine per se. We found no evidence of association in data from the GWAS migraine meta analysis consortium (n =118,710 participants) suggesting that the association might be specific to migraine co-morbid with bipolar disorder. (C) 2014 The Authors. Published by Elsevier B.V. C1 [Jacobsen, Kaya K.; Zayats, Tetyana; Haavik, Jan; Johansson, Stefan] Univ Bergen, Dept Biomed, KG Jebsen Ctr Neurophyciatr Res, Bergen, Norway. [Jacobsen, Kaya K.; Zayats, Tetyana; Johansson, Stefan] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [Fasmer, Ole Bernt; Oedegaard, Ketil J.] Univ Bergen, Dept Clin Med, KG Jebsen Ctr Neurophyciatr Res, Bergen, Norway. [Nievergelt, Caroline M.; Greenwood, Tiffany A.; Akiskal, Hagop S.; Kelsoe, John R.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Anttila, Verneri] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Anttila, Verneri] Harvard Univ, Sch Med, Boston, MA USA. [Anttila, Verneri] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Anttila, Verneri] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Akiskal, Hagop S.; Kelsoe, John R.] VA Hosp, Dept Psychiat, San Diego, CA USA. [Haavik, Jan; Fasmer, Ole Bernt; Oedegaard, Ketil J.] Haukeland Hosp, Div Psychiat, N-5021 Bergen, Norway. [Johansson, Stefan] Univ Bergen, Dept Clin Sci, N-5020 Bergen, Norway. RP Jacobsen, KK (reprint author), Univ Bergen, Dept Biomed, N-5020 Bergen, Norway. EM kja098@biomed.uib.no RI Johansson, Stefan/C-4394-2011; OI Johansson, Stefan/0000-0002-2298-7008; Nievergelt, Caroline/0000-0001-5766-8923; Kaprio, Jaakko/0000-0002-3716-2455; Wedenoja, Juho/0000-0002-6155-0378; Kaunisto, Mari/0000-0002-6946-9195; Haavik, Jan/0000-0001-7865-2808 FU NIMH; NHGRI [MH68503, MH078151, MH081804, MH059567]; Genetic Association Information Network (GAIN); UCSD General Clinical Research Center [M01 RR00827]; [R01 MH093500]; [U01 MH002758]; [K01 MH087889] FX This work was supported by grants to JRK from the NIMH and NHGRI (MH68503, MH078151, MH081804, MH059567 supplement) and by the Genetic Association Information Network (GAIN) and the UCSD General Clinical Research Center (M01 RR00827). CMN was supported by R01 MH093500 and U01 MH002758, TAG was funded by K01 MH087889. NR 62 TC 1 Z9 1 U1 0 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB 1 PY 2015 VL 172 BP 453 EP 461 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AX0LD UT WOS:000346643000063 PM 25451450 ER PT J AU Fava, M Ramey, T Pickering, E Kinrys, G Boyer, S Altstiel, L AF Fava, Maurizio Ramey, Tanya Pickering, Eve Kinrys, Gustavo Boyer, Stacey Altstiel, Larry TI A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of the Augmentation of a Nicotinic Acetylcholine Receptor Partial Agonist in Depression Is There a Relationship to Leptin Levels? SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE CP-601,927; depression; MADRS score; leptin; BMI ID OBESITY; ANTIDEPRESSANT; RESISTANCE; DISORDERS; CIGARETTE; CHOLINE; SMOKING AB This randomized, double-blind, placebo-controlled trial evaluated the efficacy of CP-601,927, an alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist and an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to selective serotonin reuptake inhibitors (SSRIs). After open-label treatment with an SSRI for 8 weeks, subjects with a Hamilton Depression Scale 17 score greater than or equal to 16 were entered into a double-blind phase and randomized to CP-601,927 2 mg twice daily or placebo for 6 weeks. The primary end point was the change in Montgomery-Asberg Depression Rating Scale (MADRS) score from double-blind baseline to week 14. There was no significant difference in change from baseline to week 14 in the MADRS score for CP-610,927 versus placebo (least square mean difference [80% confidence interval], -1.30 [-3.32-0.71]). Post hoc analyses revealed that the drug-placebo difference in change from baseline (SE) to week 14 in MADRS score was greater in subjects with body mass index (BMI) less than or equal to 35 kg/m(2) (-3.43 [1.87], P = 0.069) than those with BMI greater than 35 kg/m(2) (3.37 [2.8], P = 0.230). Analysis of biomarkers associated with increased BMI suggests that baseline leptin had a significant effect on treatment outcome. P values for the effect of treatment on mean change in MADRS score for subjects with baseline leptin levels below and above the median were 0.055 and 0.0055, respectively. CP-601,927 was equivalent to placebo as an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to SSRIs. However, post hoc analyses suggest that BMI, particularly elevated leptin levels, may have affected the response to CP-601,927; however, further study may be needed to confirm these results. C1 [Fava, Maurizio; Kinrys, Gustavo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Trials Network & Inst, Boston, MA USA. [Pickering, Eve] Pfizer Res, Biostat, Cambridge, MA USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Clin Trials Network & Inst, Bulfinch 351,55 Fruit St, Boston, MA 02114 USA. EM MFAVA@PARTNERS.ORG FU Pfizer Inc. FX The study was funded by Pfizer Inc. Eve Pickering is an employee of Pfizer Inc. Stacey Boyer is an employee of Biogen Idec. Tanya Ramey is an employee of the National Institutes of Health. Maurizio Fava and Gustavo Kinrys are employees of Harvard Medical School, Clinical Trials Network and Institute at the Massachusetts General Hospital. Larry Altstiel is an employee of Provectra Therapeutics. NR 21 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 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2015 VL 35 IS 1 BP 51 EP 56 DI 10.1097/JCP.0000000000000245 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AX5QY UT WOS:000346983200008 PM 25422883 ER PT J AU Monnelly, EP Fonda, J Gagnon, DR Chittamooru, S Lawler, EV AF Monnelly, Edward P. Fonda, Jennifer Gagnon, David R. Chittamooru, Subha Lawler, Elizabeth V. TI Weight Gain on Antipsychotic Medication Is Associated With Sustained Use Among Veterans With Schizophrenia SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; antipsychotic medications; weight change; persistence ID THERAPEUTIC RESPONSE; RANDOMIZED-TRIAL; SERUM LEPTIN; CATIE; RISPERIDONE; OLANZAPINE; ADHERENCE; DRUGS; EFFICACY; RISK AB Objective: Continuous antipsychotic treatment is important in schizophrenia, and studies have shown that rates of discontinuation are high. Some studies suggest that weight gain may lead schizophrenic patients to discontinue treatment, whereas other studies show smaller effects of weight gain on medication discontinuation, and some find weight gain associated with symptom improvement. Our retrospective cohort study investigated the effect of weight change on the continued use for 1 year (persistence) of all antipsychotics, then among users of first-generation antipsychotics and second-generation antipsychotics (SGAs), and lastly subgroups of SGAs. Methods: We identified 2130 patients with schizophrenia starting an antipsychotic that had not used 1 in the prior year. Using multivariable logistic regression adjusted for demographic and clinical variables, we determined the odds of remaining persistent on medication among patients who either gained weight or did not gain weight in the following year. Results: For all antipsychotics combined, weight change was not associated with persistence. Among SGAs, weight gain was associated with a 23% increase in the adjusted odds ratio (OR) for persistence (OR, 1.23; 95% confidence interval [CI], 1.00-1.51), whereas there was a nonsignificant decrease in the adjusted odds of persistence among first-generation antipsychotic users (OR, 0.74; 95% CI, 0.43-1.28). When SGAs were divided into subgroups (clozapine/olanzapine, risperidone/quetiapine), both had increases in the likelihood of persistence, but only the association for clozapine/olanzapine was significant at a trend level (adjusted OR, 1.46; 95% CI, 0.99-2.16). Conclusions: These findings are supportive of other research that shows weight gain does not invariably lead to medication discontinuation and may be associated with clinical improvement. C1 [Monnelly, Edward P.; Fonda, Jennifer; Gagnon, David R.; Chittamooru, Subha; Lawler, Elizabeth V.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Monnelly, Edward P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gagnon, David R.; Lawler, Elizabeth V.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lawler, Elizabeth V.] Harvard Univ, Sch Med, Boston, MA USA. [Lawler, Elizabeth V.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Monnelly, EP (reprint author), Jama Plain VA Med Ctr, Mental Hlth Serv, 150 S,Huntington Ave, Boston, MA 02130 USA. EM Edward.monnelly@va.gov FU Massachusetts Veterans Epidemiology Research and Information Center from the Veterans Health Administration Cooperative Studies Program; Wyeth Ayerst FX This study was funded by the Massachusetts Veterans Epidemiology Research and Information Center from the Veterans Health Administration Cooperative Studies Program. Additional funding was provided by Wyeth Ayerst. NR 36 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 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2015 VL 35 IS 1 BP 57 EP 62 DI 10.1097/JCP.0000000000000262 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AX5QY UT WOS:000346983200009 PM 25514067 ER PT J AU Bobo, WV Reilly-Harrington, NA Ketter, TA Brody, BD Kinrys, G Kemp, DE Shelton, RC McElroy, SL Sylvia, LG Kocsis, JH McInnis, MG Friedman, ES Singh, V Tohen, M Bowden, CL Deckersbach, T Calabrese, JR Thase, ME Nierenberg, AA Rabideau, DJ Schoenfeld, DA Faraone, SV Kamali, M AF Bobo, William V. Reilly-Harrington, Noreen A. Ketter, Terence A. Brody, Benjamin D. Kinrys, Gustavo Kemp, David E. Shelton, Richard C. McElroy, Susan L. Sylvia, Louisa G. Kocsis, James H. McInnis, Melvin G. Friedman, Edward S. Singh, Vivek Tohen, Mauricio Bowden, Charles L. Deckersbach, Thilo Calabrese, Joseph R. Thase, Michael E. Nierenberg, Andrew A. Rabideau, Dustin J. Schoenfeld, David A. Faraone, Stephen V. Kamali, Masoud TI Complexity of Illness and Adjunctive Benzodiazepine Use in Outpatients With Bipolar I or II Disorder Results From the Bipolar CHOICE Study SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE benzodiazepines; bipolar disorder; patterns of practice; treatment ID PSYCHOTROPIC-DRUG PRESCRIPTION; SEVERE MENTAL-ILLNESS; STEP-BD PARTICIPANTS; DEPRESSIVE-ILLNESS; ANXIETY DISORDERS; MOOD DISORDERS; COMORBIDITY; PATTERNS; LAMOTRIGINE; POPULATION AB Benzodiazepines are widely prescribed for patients with bipolar disorders in clinical practice, but very little is known about the subtypes of patients with bipolar disorder or aspects of bipolar illness that contribute most to benzodiazepine use. We examined the prevalence of and factors associated with benzodiazepine use among 482 patients with bipolar I or II disorder enrolled in the Bipolar CHOICE study. Eighty-one subjects were prescribed benzodiazepines at study entry and were considered benzodiazepine users. Stepwise logistic regression was used to model baseline benzodiazepine use versus nonuse, using entry and exit criteria of P < 0.1. In bivariate analyses, benzodiazepine users were prescribed a significantly higher number of other psychotropic medications and were more likely to be prescribed lamotrigine or antidepressants as compared with benzodiazepine nonusers. Benzodiazepine users were more likely to have a diagnosis of bipolar I disorder and comorbid anxiety disorder, but not comorbid alcohol or substance use disorders. Benzodiazepine users also had experienced more anxiety and depressive symptoms and suicidality, but not irritability or manic symptoms, than did benzodiazepine nonusers. In the multivariate model, anxiety symptom level (regardless of diagnosis), lamotrigine use, number of concomitant psychotropic medications, college education, and high household income predicted benzodiazepine use. Benzodiazepine use in patients with bipolar disorders is associated with greater illness complexity as indicated by a higher number of concomitant psychotropic medications and higher anxiety symptom burden, regardless of a comorbid anxiety disorder diagnosis. Demographic factors were also important determinants of benzodiazepine use, which may be related to access to care and insurance coverage for benzodiazepines. C1 [Bobo, William V.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN 55902 USA. [Reilly-Harrington, Noreen A.; Kinrys, Gustavo; Sylvia, Louisa G.; Deckersbach, Thilo; Nierenberg, Andrew A.; Rabideau, Dustin J.; Schoenfeld, David A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ketter, Terence A.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Ketter, Terence A.] Stanford Univ, Sch Med, Bipolar Disorders Clin, Stanford, CA 94305 USA. [Brody, Benjamin D.; Kocsis, James H.] Cornell Univ, Weill Cornell Med Coll, Dept Psychiat, New York, NY 10021 USA. [Kemp, David E.; Calabrese, Joseph R.] Case Western Reserve Univ, Sch Med, Dept Psychiat, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Shelton, Richard C.] Univ Alabama Birmingham, Sch Med, Dept Psychiat, Birmingham, AL USA. [McElroy, Susan L.] Lindner Ctr HOPE, Mason, OH USA. [McElroy, Susan L.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [McInnis, Melvin G.; Kamali, Masoud] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [McInnis, Melvin G.; Kamali, Masoud] Univ Michigan, Depress Ctr, Ann Arbor, MI 48109 USA. [Friedman, Edward S.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 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, Hlth Sci Ctr, Dept Psychiat, Albuquerque, NM 87131 USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. RP Bobo, WV (reprint author), Mayo Clin, Dept Psychiat & Psychol, 200 First St SW,Generose 2A, Rochester, MN 55902 USA. EM bobo.william@mayo.edu OI Faraone, Stephen/0000-0002-9217-3982 FU AstraZeneca Pharmaceuticals LP; Cephalon Inc; Eli Lilly and Company; Pfizer Inc; Sunovion Pharmaceuticals; Allergan, Inc; Avanir Pharmaceuticals; Bristol-Myers Squibb Company; Forest Pharmaceuticals; Janssen Pharmaceutica Products, LP; Merck Co, Inc; Teva Pharmaceuticals; Forest; Agency for Healthcare Research and Quality (AHRQ); Pritzker Neuropsychiatric Disorders Research Consortium; AstraZeneca; Cephalon; Elan Pharmaceuticals; Forest Pharmaceuticals Inc; GlaxoSmithKline; Sanofi/Synthelabo; Sepracor Inc; UCB Pharma; Wyeth-Ayerst Laboratories; Repligen; Roche; Takeda; Neosync; AHRQ; NIMH; NIDA; Burroughs Wellcome Trust; Pritzker Consortium; Appian Labs; BristolMyers Squibb; Elan, Corp; Euthymics Bioscience; Janssen Pharmaceutica; Naurex, Inc; Novartis Pharmaceuticals; Otsuka Pharmaceuticals; Pamlab, Inc; RepligenRepligen, Corp; Ridge Diagnostics; St Jude Medical, Inc; Takeda Pharmaceuticals; Alkermes; Marriott Foundation; National Institute of Mental Health; Orexigen Therapeutics, Inc; Pfizer; Shire; Takeda Pharmaceutical Company Ltd; Transcept Pharmaceutical, Inc; Heinz C Prechter Research Fund; Michigan Institute for Clinical Health Research (MICHR); Qatar National Research Foundation; Merck Pharmaceuticals; Novartis; St Jude Medical; Medtronics; NARSAD; TSA; OCF; Tufts University; NIH; NIA; Janssen Pharmaceuticals; Forest Research Institute; Shire Development Inc; Medtronic; Cyberonics; Northstar; Medacorp; MGH Psychiatry Academy; BrainCells Inc; Systems Research and Applications Corporation; Boston University; Catalan Agency for Health Technology Assessment and Research; National Association of Social Workers Massachusetts; Massachusetts Medical Society; Oxford University Press; Department of Defense; Health Resources Services Administration; Cleveland Foundation; Stanley Medical Research Institute; Abbott; Janssen; Eli Lilly; Lundbeck; PharmaNeuroboost; Bristol-Myers Squibb; Cederroth; Elan; Lichtwer Pharma; Pamlab; Stanley Foundation FX Dr Reilly-Harrington receives royalties from Oxford University Press, the American Psychological Association, and New Harbinger. She serves as a consultant for United Biosource Corporation and was a shareholder in Concordant Rater Systems. Dr Ketter, between May 14, 2010, and May 14, 2013, had the following financial interests/arrangements or affiliations that could be perceived as real or apparent conflicts of interest: grant/research support from AstraZeneca Pharmaceuticals LP, Cephalon Inc, Eli Lilly and Company, Pfizer Inc, and Sunovion Pharmaceuticals; consultant fees from Allergan, Inc, Avanir Pharmaceuticals, Bristol-Myers Squibb Company, Cephalon Inc, Forest Pharmaceuticals, Janssen Pharmaceutica Products, LP, Merck & Co, Inc, Sunovion Pharmaceuticals, Teva Pharmaceuticals; lecture honoraria from Abbott Laboratories, Inc, AstraZeneca Pharmaceuticals LP, GlaxoSmithKline, and Otsuka Pharmaceuticals; and Publication Royalties from American Psychiatric Publishing, Inc. In addition, Dr Ketter' s spouse is an employee of and holds stock in Janssen Pharmaceuticals. Dr Brody has received salary support over the past 3 years from grants funded by Forest, Agency for Healthcare Research and Quality (AHRQ), and Pritzker Neuropsychiatric Disorders Research Consortium. Dr Kinrys has received research support from AstraZeneca, Bristol-Myers Squibb Company, Cephalon, Elan Pharmaceuticals, Eli Lilly and Company, Forest Pharmaceuticals Inc, GlaxoSmithKline, Sanofi/Synthelabo, Sepracor Inc, Pfizer Inc, UCB Pharma, and Wyeth-Ayerst Laboratories. He has been an advisor or consultant for AstraZeneca, Cephalon, Eli Lilly and Company, Forest Pharmaceuticals Inc, GlaxoSmithKline, Janssen Pharmaceutica, Pfizer Inc, Sepracor Inc, UCB Pharma, and Wyeth-Ayerst Laboratories. Dr Kinrys has been a speaker for AstraZeneca, Forest Pharmaceuticals Inc, GlaxoSmithKline, Sepracor Inc, and Wyeth-Ayerst Laboratories. Dr Sylvia was a shareholder in Concordant Rater Systems and serves as a consultant for Bracket Global, Inc and Clintara. She also receives royalties from New Harbinger Publishers. Dr Friedman receives grant support from Repligen, AstraZeneca, Roche, Takeda, and Neosync. He has been a consultant for Pamlab. He receives royalties from Springer. He has served as an expert forensic consultant for Thomson Rhodes & Cowie P. C. and Berger and Zavesky Co. L. P. A. Dr Kocsis has received research grants and contracts from AHRQ, NIMH, NIDA, Burroughs Wellcome Trust, Pritzker Consortium, Takeda, Forest, AstraZeneca, and Roche. He is on the speaker' s bureau at Pfizer and Merck and on the advisory board at Corcept. Dr Kemp serves on the speaker's bureau for Pfizer and AstraZeneca and is a consultant for Bristol-Myers Squibb, Teva, Corcept, and Janssen. His spouse is a minor stockholder for Sanofi and Abbott. Dr Shelton has served as a consultant to Bristol-Myers Squibb, Cyberonics, Inc, Elan, Corp, Eli Lilly and Company, Euthymics Bioscience, Forest Pharmaceuticals, Janssen Pharmaceutica, Medtronic, Inc, Otsuka Pharmaceuticals, Pamlab, Inc, Pfizer, Inc, Ridge Diagnostics, and Takeda Pharmaceuticals. Dr Shelton has received research grant support from Appian Labs, BristolMyers Squibb, Elan, Corp, Eli Lilly and Company, Euthymics Bioscience, Forest Pharmaceuticals, Janssen Pharmaceutica, Naurex, Inc, Novartis Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab, Inc, Repligen, Corp, Ridge Diagnostics, St Jude Medical, Inc, and Takeda Pharmaceuticals.; Dr McElroy is a consultant to or member of the scientific advisory boards of Alkermes, Bracket, Corcept, MedAvante, Shire, Sunovian, and Teva. She is a principal or coinvestigator on studies sponsored by the AHRQ, Alkermes, AstraZeneca, Cephalon, Eli Lilly and Company, Forest, Marriott Foundation, National Institute of Mental Health, Orexigen Therapeutics, Inc, Pfizer, Shire, Takeda Pharmaceutical Company Ltd, and Transcept Pharmaceutical, Inc. She is also an inventor onUnited States Patent no. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the patent' s assignee, University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson, which has exclusive rights under the patent. Dr McInnis has received grants for research support from NIMH, the Heinz C Prechter Research Fund, and the Michigan Institute for Clinical Health Research (MICHR). He has received consulting income from the Qatar National Research Foundation and Merck Pharmaceuticals. Dr Friedman received grant support from NIMH, AHRQ, Novartis, St Jude Medical, Medtronics, Repligen, AstraZeneca, Roche, and Takeda. He receives royalties from Springer. He has been a consultant for Pamlab. Dr Singh has been a speaker for Merck and Sunovion. He has received research support from Novartis and AstraZeneca. Dr Tohen was an employee of Lilly (1997-2008) and has received honoraria from or consulted for AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Johnson & Johnson, Otsuka, Merck, Sunovion, Forest, Roche, Elan, Lundbeck, Teva, Pamlab, Wyeth, and Wiley Publishing; his spouse is a full-time employee and minor stockholder at Lilly. Dr Bowden is a research collaborator with Elan and a consultant with Teva; he has no participation with speaker bureaus, nor does he or his wife hold any equity position in any biomedical or pharmaceutical corporation. Dr Deckersbach has received research support from NIMH, NARSAD, TSA, OCF, Tufts University, NIH, NIA, Janssen Pharmaceuticals, the Forest Research Institute, Shire Development Inc, Medtronic, Cyberonics, and Northstar. He has received honoraria, consultation fees, and/or royalties from the following: Medacorp, MGH Psychiatry Academy, BrainCells Inc, Systems Research and Applications Corporation, Boston University, Tufts University, the Catalan Agency for Health Technology Assessment and Research, the National Association of Social Workers Massachusetts, the Massachusetts Medical Society, and Oxford University Press. Dr Calabrese receives federal funding from the Department of Defense, Health Resources Services Administration, and NIMH; he receives research funding or grants from the following private industries or nonprofit funds: Cleveland Foundation, NARSAD, and Stanley Medical Research Institute; he receives research grants from Abbott, AstraZeneca, Cephalon, GlaxoSmithKline, Janssen, Eli Lilly, and Lundbeck; he serves on the advisory boards of Abbott, AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Forest, France Foundation, GlaxoSmithKline, Janssen, NeuroSearch, OrthoMcNeil, Repligen, Schering-Plough, Servier, Solvay/Wyeth, Takeda, and Supernus Pharmaceuticals; and he reports CME activities with AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen, Johnson & Johnson, Schering-Plough, and Solvay/Wyeth.; Dr Thase has been an advisor/consultant: to Alkermes, AstraZeneca, BristolMyers Squibb, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck, MedAvante, Merck, Mylan, Neuronetics, Otsuka, Pamlab, PharmaNeuroboost, Pfizer, Rexahn, Roche, Shire, Sunovion, Supernus, Takeda, and Teva, as well as the US Food and Drug Administration and the National Institute of Mental Health. During the same time frame, Dr Thase has received honoraria for talks from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, and Pfizer and he has received research grants from Alkermes, AstraZeneca, Eli Lilly, Forest, GlaxoSmithKline, Otsuka, PharmaNeuroboost, and Roche, as well as the National Institute of Mental Health and the AHRQ. Dr Nierenberg is a consultant for Abbott Laboratories, AstraZeneca, Basilea, BrainCells Inc, Brandeis University, Bristol-Myers Squibb, Cephalon, Corcept, Eli Lilly and Company, Forest, Genaissance, GlaxoSmithKline, Innapharma, Janssen Pharmaceutica, Jazz Pharmaceuticals, Lundbeck, Merck, Novartis, Pamlab, PGx Health, Pfizer, Ridge Diagnostics, Roche, Sepracor, ScheringPlough, Shire, Somerset, Sunovion, Takeda, Targacept, and Teva. He is a stakeholder in Appliance Computing, Inc (MindSite); Brain Cells, Inc, InfoMed (potential share of income). He receives research support from AHRQ, Bristol-Myers Squibb, Cederroth, Cyberonics, Elan, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Lichtwer Pharma, Eli Lilly, Mylin (formerly Dey Pharmaceuticals), NARSAD, NIMH, Pamlab, Pfizer, Shire, Stanley Foundation, and Wyeth-Ayerst. Honoraria include MGH Psychiatry Academy in the past 3 years (prior to these, 3 years ago, he received honoraria from Bristol-Myers Squibb, Cyberonics, Forest Pharmaceuticals, GlaxoSmithKline, Eli Lilly, Shire, and WyethAyerst). Dr Nierenberg receives other income from legal case reviews for CRICO, MBL Publishing for past services as Editor-in-Chief of CNS Spectrums, Slack Inc for services as Associate Editor of Psychiatric Annals, and Editorial Board, Mind Mood Memory, Belvior Publications. He has copyright joint ownership with MGH for Structured Clinical Interview for MADRS and Clinical Positive Affect Scale and additional honoraria from ADURS, American Society for Clinical Psychopharmacology and Zucker Hillside Hospital and Forest and Janssen, Biomedical Development, Boston Center for the Arts, University of Pisa, University of Wisconsin at Madison, University Texas Southwest atDallas, Health New England and Harold Grinspoon Charitable Foundation and Eli Lilly and AstraZeneca, Brandeis University, International Society for Bipolar Disorder, 2nd East Asian Bipolar Forum, MidAtlantic Permanente Research Institute, Up-to-Date. Dr Schoenfeld has an ongoing consulting relationship with the following pharmaceutical companies: Biogen, Neuronova, Cytokinetics, Edison Pharmaceuticals, GlaxoSmithKline, Merck, Agennix, Alexion, and Pfizer. He also has a consulting relationship with Aptiv, a contract research organization. Dr Bobo, Mr Rabideau, and Dr Kamali report no competing interests in the past 3 years. NR 30 TC 2 Z9 2 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2015 VL 35 IS 1 BP 68 EP 74 DI 10.1097/JCP.0000000000000257 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AX5QY UT WOS:000346983200011 PM 25514063 ER PT J AU Wijeakumar, S Spencer, JP Bohache, K Boas, DA Magnotta, VA AF Wijeakumar, Sobanawartiny Spencer, John P. Bohache, Kevin Boas, David A. Magnotta, Vincent A. TI Validating a new methodology for optical probe design and image registration in fNIRS studies SO NEUROIMAGE LA English DT Article DE Functional near infrared spectroscopy; Probe geometry; Optode co-registration; Visual working memory; AtlasViewerGUI ID NEAR-INFRARED SPECTROSCOPY; WORKING-MEMORY; HEMODYNAMIC-RESPONSES; BRAIN; STIMULI; INFANTS AB Functional near-infrared spectroscopy (fNIRS) is an imaging technique that relies on the principle of shining near-infrared light through tissue to detect changes in hemodynamic activation. An important methodological issue encountered is the creation of optimized probe geometry for fNIRS recordings. Here, across three experiments, we describe and validate a processing pipeline designed to create an optimized, yet scalable probe geometry based on selected regions of interest (ROIs) from the functional magnetic resonance imaging (fMRI) literature. In experiment 1, we created a probe geometry optimized to record changes in activation from target ROIs important for visual working memory. Positions of the sources and detectors of the probe geometry on an adult head were digitized using a motion sensor and projected onto a generic adult atlas and a segmented head obtained from the subject's MRI scan. In experiment 2, the same probe geometry was scaled down to fit a child's head and later digitized and projected onto the generic adult atlas and a segmented volume obtained from the child's MRI scan. Using visualization tools and by quantifying the amount of intersection between target ROIs and channels, we show that out of 21 ROIs, 17 and 19 ROIs intersected with fNIRS channels from the adult and child probe geometries, respectively. Further, both the adult atlas and adult subject-specific MRI approaches yielded similar results and can be used interchangeably. However, results suggest that segmented heads obtained from MRI scans be used for registering children's data. Finally, in experiment 3, we further validated our processing pipeline by creating a different probe geometry designed to record from target ROIs involved in language and motor processing. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wijeakumar, Sobanawartiny; Spencer, John P.; Bohache, Kevin] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Wijeakumar, Sobanawartiny; Spencer, John P.; Bohache, Kevin; Magnotta, Vincent A.] Univ Iowa, Delta Ctr, Iowa City, IA 52242 USA. [Magnotta, Vincent A.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. [Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA. RP Wijeakumar, S (reprint author), Univ Iowa, Dept Psychol, E1 Seashore Hall, Iowa City, IA 52245 USA. EM sobanawartiny-wijeakumar@uiowa.edu FU NSF [HSD0527698]; NIH [P41 EB015896] FX JPS acknowledges support from NSF HSD0527698.; DAB acknowledges support from NIH P41 EB015896. NR 34 TC 3 Z9 3 U1 0 U2 14 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 FEB 1 PY 2015 VL 106 BP 86 EP 100 DI 10.1016/j.neuroimage.2014.11.022 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AX7NG UT WOS:000347101900008 PM 25705757 ER PT J AU Aganj, I Reuter, M Sabuncu, MR Fischl, B AF Aganj, Iman Reuter, Martin Sabuncu, Mert R. Fischl, Bruce TI Avoiding symmetry-breaking spatial non-uniformity in deformable image registration via a quasi-volume-preserving constraint SO NEUROIMAGE LA English DT Article DE Deformable image registration; Volume-preserving constraints; Symmetry; Inverse-consistency; Integral non-uniformity ID LOCALLY ADAPTIVE REGULARIZATION; SURFACE-BASED ANALYSIS; FREE-FORM DEFORMATION; NONRIGID REGISTRATION; DIFFEOMORPHIC REGISTRATION; SEGMENTATION; ALGORITHM; DEMONS; BRAIN; CONSTRUCTION AB The choice of a reference image typically influences the results of deformable image registration, thereby making it asymmetric. This is a consequence of a spatially non-uniform weighting in the cost function integral that leads to general registration inaccuracy. The inhomogeneous integral measure - which is the local volume change in the transformation, thus varying through the course of the registration - causes image regions to contribute differently to the objective function. More importantly, the optimization algorithm is allowed to minimize the cost function by manipulating the volume change, instead of aligning the images. The approaches that restore symmetry to deformable registration successfully achieve inverse-consistency, but do not eliminate the regional bias that is the source of the error. In this work, we address the root of the problem: the non-uniformity of the cost function integral. We introduce a new quasi-volume-preserving constraint that allows for volume change only in areas with well-matching image intensities, and show that such a constraint puts a bound on the error arising from spatial non-uniformity. We demonstrate the advantages of adding the proposed constraint to standard (asymmetric and symmetrized) demons and diffeomorphic demons algorithms through experiments on synthetic images, and real X-ray and 2D/3D brain MRI data. Specifically, the results show that our approach leads to image alignment with more accurate matching of manually defined neuroanatomical structures, better tradeoff between image intensity matching and registration-induced distortion, improved native symmetry, and lower susceptibility to local optima. In summary, the inclusion of this space-and time-varying constraint leads to better image registration along every dimension that we have measured it. (C) 2014 Elsevier Inc. All rights reserved. C1 [Aganj, Iman; Reuter, Martin; Sabuncu, Mert R.; Fischl, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Radiol De, Charlestown, MA 02129 USA. [Reuter, Martin; Sabuncu, Mert R.; Fischl, Bruce] MIT, Dept Elect Engn & Comp Sci, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Fischl, Bruce] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Aganj, I (reprint author), 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM iman@nmr.mgh.harvard.edu; mreuter@nmr.mgh.harvard.edu; msabuncu@nmr.mgh.harvard.edu; fischl@nmr.mgh.harvard.edu RI Reuter, Martin/B-3456-2010 OI Reuter, Martin/0000-0002-2665-9693 FU National Center for Research Resources [U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering (NIBIB) [P41-EB015896, R01EB006758]; National Institute on Aging [AG022381, 5R01AG008122-22, R01 AG016495-11]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963, R01NS083534]; Autism & Dyslexia Project - Ellison Medical Foundation; NIH Blueprint for Neuroscience Research [5U01-MH093765]; Massachusetts Alzheimer's Disease Research Center [5 P50 AG005134]; Massachusetts General Hospital (MGH) Neurology Clinical Trials Unit; Harvard NeuroDiscovery Center; NIBIB K25 grant [1K25EB013649-01]; BrightFocus Alzheimer's Disease Pilot grant [A2012333]; [1S10RR023401]; [1S10RR019307]; [1S10RR023043] FX Support for this research was provided in part by the National Center for Research Resources (U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (NIBIB, P41-EB015896, R01EB006758), the National Institute on Aging (AG022381, 5R01AG008122-22, R01 AG016495-11), the National Center for Alternative Medicine (RC1 AT005728-01), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963, R01NS083534), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation, and by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. IA was additionally supported by a grant from the Massachusetts Alzheimer's Disease Research Center (5 P50 AG005134), the Massachusetts General Hospital (MGH) Neurology Clinical Trials Unit, and the Harvard NeuroDiscovery Center. MS received support from an NIBIB K25 grant (1K25EB013649-01) and a BrightFocus Alzheimer's Disease Pilot grant (A2012333). In addition, BF has a financial interest in CorticoMetrics, a company whose medical pursuits focus on brain imaging and measurement technologies. BF's interests were reviewed and are managed by MGH and Partners HealthCare in accordance with their conflict of interest policies. NR 80 TC 2 Z9 3 U1 1 U2 9 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 FEB 1 PY 2015 VL 106 BP 238 EP 251 DI 10.1016/j.neuroimage.2014.10.059 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AX7NG UT WOS:000347101900022 PM 25449738 ER PT J AU De Winter, FL Zhu, Q Van den Stock, J Nelissen, K Peeters, R de Gelder, B Vanduffel, W Vandenbulcke, M AF De Winter, Francois-Laurent Zhu, Qi Van den Stock, Jan Nelissen, Koen Peeters, Ronald de Gelder, Beatrice Vanduffel, Wim Vandenbulcke, Mathieu TI Lateralization for dynamic facial expressions in human superior temporal sulcus SO NEUROIMAGE LA English DT Article DE Lateralization; Dynamic facial expressions; Comparative; fMRI ID FUSIFORM FACE AREA; CHIMPANZEES PAN-TROGLODYTES; HUMAN BRAIN; LANGUAGE DOMINANCE; RIGHT-HEMISPHERE; FUNCTIONAL MRI; CEREBRAL LATERALIZATION; MACAQUE CORTEX; PERCEPTION; FMRI AB Most face processing studies in humans show stronger activation in the right compared to the left hemisphere. Evidence is largely based on studies with static stimuli focusing on the fusiform face area (FFA). Hence, the pattern of lateralization for dynamic faces is less clear. Furthermore, it is unclear whether this property is common to human and non-human primates due to predisposing processing strategies in the right hemisphere or that alternatively left sided specialization for language in humans could be the driving force behind this phenomenon. We aimed to address both issues by studying lateralization for dynamic facial expressions in monkeys and humans. Therefore, we conducted an event-related fMRI experiment in three macaques and twenty right handed humans. We presented human and monkey dynamic facial expressions (chewing and fear) as well as scrambled versions to both species. We studied lateralization in independently defined face-responsive and face-selective regions by calculating a weighted lateralization index (LIwm) using a bootstrapping method. In order to examine if lateralization in humans is related to language, we performed a separate fMRI experiment in ten human volunteers including a 'speech' expression (one syllable non-word) and its scrambled version. Both within face-responsive and selective regions, we found consistent lateralization for dynamic faces (chewing and fear) versus scrambled versions in the right human posterior superior temporal sulcus (pSTS), but not in FFA nor in ventral temporal cortex. Conversely, in monkeys no consistent pattern of lateralization for dynamic facial expressions was observed. Finally, LIwms based on the contrast between different types of dynamic facial expressions (relative to scrambled versions) revealed left-sided lateralization in human pSTS for speech-related expressions compared to chewing and emotional expressions. To conclude, we found consistent laterality effects in human posterior STS but not in visual cortex of monkeys. Based on our results, it is tempting to speculate that lateralization for dynamic face processing in humans may be driven by left-hemispheric language specialization which may not have been present yet in the common ancestor of human and macaque monkeys. (C) 2014 Elsevier Inc. All rights reserved. C1 [De Winter, Francois-Laurent; Van den Stock, Jan; de Gelder, Beatrice; Vandenbulcke, Mathieu] Katholieke Univ Leuven, Dept Neurosci, Res Grp Psychiat, B-3000 Leuven, Belgium. [De Winter, Francois-Laurent; Van den Stock, Jan; Vandenbulcke, Mathieu] Univ Hosp Leuven, Dept Old Age Psychiat, B-3000 Leuven, Belgium. [Zhu, Qi; Nelissen, Koen; Vanduffel, Wim] Katholieke Univ Leuven, Dept Neurosci, Lab Neuro & Psychophysiol, B-3000 Leuven, Belgium. [Peeters, Ronald] UZ Leuven, Dept Radiol, B-3000 Leuven, Belgium. [Peeters, Ronald] Katholieke Univ Leuven, Dept Imaging & Pathol, B-3000 Leuven, Belgium. [de Gelder, Beatrice] Maastricht Univ, Dept Cognit Neurosci, NL-6200 MD Maastricht, Netherlands. [de Gelder, Beatrice] Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands. [Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP De Winter, FL (reprint author), Katholieke Univ Leuven, Dept Neurosci, Res Grp Psychiat, Herestr 49,Box 1027, B-3000 Leuven, Belgium. EM francoislaurent.dewinter@med.kuleuven.be RI Van den Stock, Jan/F-1906-2014 OI Van den Stock, Jan/0000-0001-5756-3195 FU Fund for Scientific Research (Flanders) [G043912, G074609, G062208, G083111]; Hercules II Funding; Inter University Attraction Pole [7/11] FX We thank C. Fransen, C. Van Eupen and A. Coeman for animal training and care; and D. Mantini, H. Kolster, W. Depuydt, G. Meulemans, P. Kayenbergh, M. De Paep, S. Verstraeten, and I. Puttemans for technical assistance. This work was supported by the Fund for Scientific Research (Flanders) G043912, G074609, G062208, and G083111, Hercules II Funding, Inter University Attraction Pole 7/11. Q.Z. and J.V.d.S. are post-doctoral fellows of the FWO Vlaanderen. NR 70 TC 17 Z9 17 U1 6 U2 33 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 FEB 1 PY 2015 VL 106 BP 340 EP 352 DI 10.1016/j.neuroimage.2014.11.020 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AX7NG UT WOS:000347101900031 PM 25463458 ER PT J AU Iglesias, JE Sabuncu, MR Aganj, I Bhatt, P Casillas, C Salat, D Boxer, A Fischl, B Van Leemput, K AF Eugenio Iglesias, Juan Sabuncu, Mert Rory Aganj, Iman Bhatt, Priyanka Casillas, Christen Salat, David Boxer, Adam Fischl, Bruce Van Leemput, Koen TI An algorithm for optimal fusion of atlases with different labeling protocols SO NEUROIMAGE LA English DT Article DE Segmentation; Label fusion ID SPATIALLY VARYING PERFORMANCE; HUMAN-BRAIN; IMAGE SEGMENTATION; HIPPOCAMPAL SUBFIELDS; STATISTICAL FUSION; ALZHEIMERS-DISEASE; MRI; AGE; PROBABILITY; SELECTION AB In this paper we present a novel label fusion algorithm suited for scenarios in which different manual delineation protocols with potentially disparate structures have been used to annotate the training scans (hereafter referred to as "atlases"). Such scenarios arise when atlases have missing structures, when they have been labeled with different levels of detail, or when they have been taken from different heterogeneous databases. The proposed algorithm can be used to automatically label a novel scan with any of the protocols from the training data. Further, it enables us to generate new labels that are not present in any delineation protocol by defining intersections on the underling labels. We first use probabilistic models of label fusion to generalize three popular label fusion techniques to the multi-protocol setting: majority voting, semi-locally weighted voting and STAPLE. Then, we identify some shortcomings of the generalized methods, namely the inability to produce meaningful posterior probabilities for the different labels (majority voting, semi-locally weighted voting) and to exploit the similarities between the atlases (all three methods). Finally, we propose a novel generative label fusion model that can overcome these drawbacks. We use the proposed method to combine four brain MRI datasets labeled with different protocols (with a total of 102 unique labeled structures) to produce segmentations of 148 brain regions. Using cross-validation, we show that the proposed algorithm outperforms the generalizations of majority voting, semi-locally weighted voting and STAPLE (mean Dice score 83%, vs. 77%, 80% and 79%, respectively). We also evaluated the proposed algorithm in an aging study, successfully reproducing some well-known results in cortical and subcortical structures. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Eugenio Iglesias, Juan] Basque Ctr Cognit Brain & Language BCBL, Gipuzkoa, Spain. [Sabuncu, Mert Rory; Aganj, Iman; Salat, David; Fischl, Bruce; Van Leemput, Koen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Bhatt, Priyanka; Casillas, Christen; Boxer, Adam] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Sabuncu, Mert Rory; Fischl, Bruce] MIT, CSAIL, Cambridge, MA 02139 USA. [Van Leemput, Koen] Tech Univ Denmark, Dept Appl Math & Comp Sci, Odense, Denmark. [Van Leemput, Koen] Aalto Univ, Dept Informat & Comp Sci, Espoo, Finland. [Van Leemput, Koen] Aalto Univ, Dept Biomed Engn & Computat Sci, Espoo, Finland. RP Iglesias, JE (reprint author), Basque Ctr Cognit Brain & Language BCBL, Gipuzkoa, Spain. EM e.iglesias@bcbl.eu RI Van Leemput, Koen/A-9197-2009; Iglesias, Juan Eugenio/K-1184-2014 OI Van Leemput, Koen/0000-0001-6466-5309; Iglesias, Juan Eugenio/0000-0001-7569-173X FU National Center for Research Resources [U24 RR021382, P41-RR14075, 1KL2RR025757-01]; National Institute for Biomedical Imaging and Bioengineering [P41-EB015896, R01EB006758, R01EB013565, 1K25EB013649-01]; National Institute on Aging [AG022381, 5R01AG008122-22, R01 AG016495-11]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS 072652-01, 1R01NS070963, R01NS083534]; Autism & Dyslexia Project - Ellison Medical Foundation; NIH Blueprint for Neuroscience Research [5U01-MH093765]; TEKES (ComBrain); Harvard Catalyst; Harvard; Gipuzkoako Foru Aldundia; BrightFocus grant [AHAF-A2012333]; [1S10RR023401]; [1S10RR019307]; [1S10RR023043] FX Support for this research was provided in part by the National Center for Research Resources (U24 RR021382, P41-RR14075, 1KL2RR025757-01), the National Institute for Biomedical Imaging and Bioengineering (P41-EB015896, R01EB006758, R01EB013565, 1K25EB013649-01), the National Institute on Aging (AG022381, 5R01AG008122-22, R01 AG016495-11), the National Center for Alternative Medicine (RC1 AT005728-01), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS 072652-01, 1R01NS070963, R01NS083534), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation, and by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. This research was also funded by TEKES (ComBrain), Harvard Catalyst, and financial contributions from Harvard and affiliations. JEI was supported by the Gipuzkoako Foru Aldundia (Fellows Gipuzkoa Program). MRS was partially supported by a BrightFocus grant (AHAF-A2012333). In addition, BF has a financial interest in CorticoMetrics, a company whose medical pursuits focus on brain imaging and measurement technologies. BF's interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. NR 42 TC 2 Z9 2 U1 0 U2 7 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 FEB 1 PY 2015 VL 106 BP 451 EP 463 DI 10.1016/j.neuroimage.2014.11.031 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AX7NG UT WOS:000347101900041 PM 25463466 ER PT J AU Huang, SY Nummenmaa, A Witzel, T Duval, T Cohen-Adad, J Wald, LL Mcnab, JA AF Huang, Susie Y. Nummenmaa, Aapo Witzel, Thomas Duval, Tanguy Cohen-Adad, Julien Wald, Lawrence L. McNab, Jennifer A. TI The impact of gradient strength on in vivo diffusion MRI estimates of axon diameter SO NEUROIMAGE LA English DT Article ID HUMAN CONNECTOME PROJECT; HUMAN CORPUS-CALLOSUM; AMYOTROPHIC-LATERAL-SCLEROSIS; AUTISM SPECTRUM DISORDERS; BRAIN WHITE-MATTER; WEIGHTED MR; FIBER COMPOSITION; MICROSTRUCTURE SENSITIVITY; RESTRICTED DIFFUSION; WATER RELAXATION AB Diffusion magnetic resonance imaging (MRI) methods for axon diameter mapping benefit from higher maximum gradient strengths than are currently available on commercial human scanners. Using a dedicated high-gradient 3 T human MRI scanner with a maximum gradient strength of 300 mT/m, we systematically studied the effect of gradient strength on in vivo axon diameter and density estimates in the human corpus callosum. Pulsed gradient spin echo experiments were performed in a single scan session lasting approximately 2 h on each of three human subjects. The data were then divided into subsets with maximum gradient strengths of 77, 145, 212, and 293 mT/m and diffusion times encompassing short (16 and 25 ms) and long (60 and 94 ms) diffusion time regimes. A three-compartment model of intra-axonal diffusion, extra-axonal diffusion, and free diffusion in cerebrospinal fluid was fitted to the data using a Markov chain Monte Carlo approach. For the acquisition parameters, model, and fitting routine used in our study, it was found that higher maximum gradient strengths decreased the mean axon diameter estimates by two to three fold and decreased the uncertainty in axon diameter estimates by more than half across the corpus callosum. The exclusive use of longer diffusion times resulted in axon diameter estimates that were up to two times larger than those obtained with shorter diffusion times. Axon diameter and density maps appeared less noisy and showed improved contrast between different regions of the corpus callosum with higher maximum gradient strength. Known differences in axon diameter and density between the genu, body, and splenium of the corpus callosum were preserved and became more reproducible at higher maximum gradient strengths. Our results suggest that an optimal q-space sampling scheme for estimating in vivo axon diameters should incorporate the highest possible gradient strength. The improvement in axon diameter and density estimates that we demonstrate from increasing maximum gradient strength will inform protocol development and encourage the adoption of higher maximum gradient strengths for use in commercial human scanners. (C) 2014 Elsevier Inc. All rights reserved. C1 [Huang, Susie Y.; Nummenmaa, Aapo; Witzel, Thomas; Wald, Lawrence L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02138 USA. [Duval, Tanguy; Cohen-Adad, Julien] Ecole Polytech, Inst Biomed Engn, Montreal, PQ H3C 3A7, Canada. [Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [McNab, Jennifer A.] Stanford Univ, Dept Radiol, Radiol Sci Lab, Stanford, CA 94305 USA. RP Huang, SY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02138 USA. EM syhuang@nmr.mgh.harvard.edu RI Witzel, Thomas/P-1402-2014; Wald, Lawrence/D-4151-2009 FU NIH Blueprint for Neuroscience Research Grant [U01MH093765]; NIH from NCRR [P41EB015896]; NIBIB [R01EB006847, K99EB015445]; Canadian Institute for Health Research; RSNA Research Resident Grant FX This work was funded by an NIH Blueprint for Neuroscience Research Grant: U01MH093765, as well as NIH funding from NCRR P41EB015896, NIBIB R01EB006847, and NIBIB K99EB015445. Funding support was also received from a fellowship from the Canadian Institute for Health Research and an RSNA Research Resident Grant. We thank Eric Klawiter, Jonathan Polimeni, and Bruce Rosen for helpful discussions on this material. NR 72 TC 22 Z9 22 U1 3 U2 25 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 FEB 1 PY 2015 VL 106 BP 464 EP 472 DI 10.1016/j.neuroimage.2014.12.008 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AX7NG UT WOS:000347101900042 PM 25498429 ER PT J AU Bredella, MA Azevedo, DC Oliveira, AL Simeone, FJ Chang, CY Stubbs, AJ Torriani, M AF Bredella, Miriam A. Azevedo, Debora C. Oliveira, Adriana L. Simeone, Frank J. Chang, Connie Y. Stubbs, Allston J. Torriani, Martin TI Pelvic morphology in ischiofemoral impingement SO SKELETAL RADIOLOGY LA English DT Article DE Ischiofemoral impingement; Hip; MRI; Quadratus femoris muscle ID QUADRATUS FEMORIS MUSCLE; LESSER TROCHANTER; HIP PAIN; PELVIMETRY AB To assess MRI measures to quantify pelvic morphology that may predispose to ischiofemoral impingement (IFI). We hypothesized that patients with IFI have a wider interischial distance and an increased femoral neck angle compared with normal controls. The study was IRB-approved and complied with HIPAA guidelines. IFI was diagnosed based on clinical findings (hip or buttock pain) and ipsilateral edema of the quadratus femoris muscle on MRI. Control subjects did not report isolated hip/buttock pain and underwent MRI for surveillance of neoplasms or to exclude pelvic fractures. Two MSK radiologists measured the ischiofemoral (IF) and quadratus femoris (QF) distance, the ischial angle as a measure of inter-ischial distance, and the femoral neck angle. The quadratus femoris muscle was evaluated for edema. Groups were compared using ANOVA. Multivariate standard least-squares regression modeling was used to control for age and gender. The study group comprised 84 patients with IFI (53 +/- 16 years, 73 female, 11 male) and 51 controls (52 +/- 16 years, 33 female, 18 male). Thirteen out of 84 patients (15 %) had bilateral IFI. Patients with IFI had decreased IF and QF distance (p < 0.0001), increased ischial angle (p = 0.004), and increased femoral neck angle (p = 0.02) compared with controls, independent of age and gender. Patients with IFI have increased ischial and femoral neck angles compared with controls. These anatomical variations in pelvic morphology may predispose to IFI. MRI is a useful method of not only assessing the osseous and soft-tissue abnormalities associated with IFI, but also of quantifying anatomical variations in pelvic morphology that can predispose to IFI. C1 [Bredella, Miriam A.; Azevedo, Debora C.; Oliveira, Adriana L.; Simeone, Frank J.; Chang, Connie Y.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Stubbs, Allston J.] Wake Forest Univ, Bowman Gray Sch Med, Div Sports Med, Dept Orthoped Surg, Winston Salem, NC USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol Musculoskeletal Imaging & Intervent, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org NR 14 TC 15 Z9 16 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 FEB PY 2015 VL 44 IS 2 BP 249 EP 253 DI 10.1007/s00256-014-2041-0 PG 5 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA AX4LQ UT WOS:000346904500011 PM 25371087 ER PT J AU Arterburn, D Wellman, R Westbrook, EO Ross, TR McCulloch, D Handley, M Lowe, M Cable, C Zeliadt, SB Hoffman, RM AF Arterburn, David Wellman, Robert Westbrook, Emily O. Ross, Tyler R. McCulloch, David Handley, Matt Lowe, Marc Cable, Chris Zeliadt, Steven B. Hoffman, Richard M. TI Decision Aids for Benign Prostatic Hyperplasia and Prostate Cancer SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CLINICAL-PRACTICE; MANAGEMENT; UPDATE; HEALTH; GUIDELINE; BARRIERS; CARE; MEN AB Objectives To examine the relationships among implementing decision aids (DAs) for benign prostatic hyperplasia (BPH) and prostate cancer (PRCA), and treatment rates and costs. Study Design A pre-post observational evaluation of a quality improvement initiative in a healthcare system in Washington state. Methods Men with BPH seen in urology clinics and all men diagnosed with localized PRCA were identified for an intervention period, in which urologists were instructed to order a DA for every patient with those conditions, and a historical control period. Outcomes were 6-month rates of surgery for BPH, any active treatment (hormone therapy, radiation, or surgery) for PRCA, and total healthcare costs. Results During the intervention, DAs were delivered to 22% of men with recent BPH drug treatment, 24% of men with untreated BPH, and 56% of men with PRCA. DA implementation was associated with a 32% lower rate of surgery among men with treated BPH (rate ratio [RR], 0.68; 95% CI, 0.49-0.94) and a nonsignificant 22% lower rate of surgery among men with previously untreated BPH (RR, 0.78; 95% CI, 0.50-1.22). For PRCA, DA implementation was associated with a 27% lower rate of active treatment (RR, 0.73; 95% CI, 0.57-0.93). We found no significant associations between DA implementation and costs of care for either condition. Conclusions Implementing patient DAs was associated with lower rates of elective surgery for previously treated BPH and active treatment for localized PRCA; however, implementation of these DAs was not associated with lower costs of care. C1 [Arterburn, David; Wellman, Robert; Westbrook, Emily O.; Ross, Tyler R.] Grp Hlth Res Inst, 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA. [McCulloch, David; Handley, Matt; Lowe, Marc; Cable, Chris] Grp Hlth Phys, Seattle, WA USA. [Zeliadt, Steven B.] VA Puget Sound Hlth Care Syst, Northwest HSR&D Ctr Excellence, Seattle, WA USA. [Hoffman, Richard M.] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. [Hoffman, Richard M.] New Mexico VA Hlth Care Syst, Med Serv, Albuquerque, NM USA. RP Arterburn, D (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA. EM arterburn.d@ghc.org FU The Commonwealth Fund [20080479]; Informed Medical Decisions Foundation [0103]; Group Health Foundation FX This work was funded by The Commonwealth Fund (Grant #20080479), the Informed Medical Decisions Foundation (Grant #0103), and the Group Health Foundation. The decision aids used in this study were provided by Health Dialog, Inc. The authors had full access to all of the data and the funders did not have control over manuscript drafting or publication. NR 25 TC 0 Z9 1 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD FEB PY 2015 VL 21 IS 2 BP E130 EP + PG 13 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DR4XM UT WOS:000379906800006 PM 25880488 ER PT J AU Grant, RW Huang, ES Wexler, DJ Laiteerapong, N Warton, EM Moffet, HH Karter, AJ AF Grant, Richard W. Huang, Elbert S. Wexler, Deborah J. Laiteerapong, Neda Warton, E. Margaret Moffet, Howard H. Karter, Andrew J. TI Patients Who Self-Monitor Blood Glucose and Their Unused Testing Results SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID TYPE-2 DIABETIC-PATIENTS; NORTHERN-CALIFORNIA; GLYCEMIC CONTROL; PRIMARY-CARE; VALIDITY; RELIABILITY; HEALTH; TIME; COMMUNICATION; VALIDATION AB Objectives To investigate the prevalence, predictors, and costs associated with unused results from self-monitoring of blood glucose (SMBG). Study Design Observational cohort study. Methods We studied 7320 patients with type 2 diabetes mellitus who were not prescribed insulin and who reported SMBG. Patients reported whether they used SMBG results to make adjustments to diet, exercise, or medicines; and whether their physician/provider reviewed their SMBG results. We categorized SMBG results as "used" (by patient and/or provider) or "unused" (not used by either patient or provider). Results SMBG results were unused by patient and provider in 15.2% of patients. In separate models adjusted for demographic and clinical differences, major predictors of SMBG without patient or physician using the results included a patient reporting that diabetes was not a high priority (relative risk [RR], 1.81; 95% CI, 1.58-2.07); the physician not engaging in shared decision making (RR, 1.66; 95% CI, 1.46-1.90); and no healthcare professional teaching the patient how to adjust diet/medicines based on SMBG results in the past year (RR, 2.27; 95% CI, 2.00-2.57). Patients with unused results were dispensed 171 +/- 191 test strips per year at an estimated annual cost of $168. Conclusions Nearly 1 in 6 non-insulin-treated patients practiced SMBG without either the patient or physician using the results. This represents a wasteful and ineffective practice for patients and health systems alike. Our results suggest that the decision to initiate and continue SMBG must be made in concert with the patient's own priorities, and, if prescribed, SMBG requires effective patient-provider communication and patient education. C1 [Grant, Richard W.; Warton, E. Margaret; Moffet, Howard H.; Karter, Andrew J.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Huang, Elbert S.; Laiteerapong, Neda] Univ Chicago, Dept Med, Gen Internal Med Sect, Chicago, IL 60637 USA. [Wexler, Deborah J.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Wexler, Deborah J.] Harvard Med Sch, Boston, MA USA. RP Grant, RW (reprint author), 2101 Webster St,20th Fl, Oakland, CA 94612 USA. EM Richard.W.Grant@kp.org FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK-081796, R01-DK080726, R01-DK-065664, R01-HD46113]; NIDDK Centers for Diabetes Translation Research at Kaiser Permanente and University of California, San Francisco [P30 DK092924]; University of Chicago [P30 DK092949] FX This work was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01-DK-081796, R01-DK080726, R01-DK-065664, and R01-HD46113). Investigators were also supported by NIDDK Centers for Diabetes Translation Research at Kaiser Permanente and University of California, San Francisco (P30 DK092924) and the University of Chicago (P30 DK092949). NR 31 TC 5 Z9 5 U1 1 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD FEB PY 2015 VL 21 IS 2 BP E119 EP E129 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DR4XM UT WOS:000379906800005 PM 25880487 ER PT J AU Tsai, JN Yu, EW Derrico, N Martinez-Betancourt, A Bouxsein, ML AF Tsai, J. N. Yu, E. W. Derrico, N. Martinez-Betancourt, A. Bouxsein, M. L. TI IN VIVO CORTICAL BONE INDENTATION MEASUREMENTS ARE INDEPENDENT OF AGE, BMD AND CORTICAL MORPHOLOGY IN POSTMENOPAUSAL WOMEN SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO) CY MAR 26-29, 2015 CL Milan, ITALY SP WCO, IOF, EsCEO C1 [Tsai, J. N.; Yu, E. W.; Derrico, N.; Martinez-Betancourt, A.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bouxsein, M. L.] Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD FEB PY 2015 VL 26 SU 1 MA OC19 BP S46 EP S47 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DI8QX UT WOS:000373767100028 ER PT J AU Bauer, MS Lee, A Miller, CJ Bajor, L Li, MF Penfold, RB AF Bauer, Mark S. Lee, Austin Miller, Christopher J. Bajor, Laura Li, Mingfei Penfold, Robert B. TI Effects of Diagnostic Inclusion Criteria on Prevalence and Population Characteristics in Database Research SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VS. UNSTRUCTURED INTERVIEWS; NATIONAL-COMORBIDITY-SURVEY; BIPOLAR AFFECTIVE-DISORDER; MENTAL-HEALTH-SERVICES; ADMINISTRATIVE DATA; 12-MONTH PREVALENCE; SCHIZOPHRENIA; VETERANS; DEPRESSION AB Objectives: Studies of serious mental illnesses that use administrative databases have employed various criteria to establish diagnoses of interest. Several studies have assessed the validity of diagnostic inclusion criteria against research diagnoses. However, no studies have examined the effect of diagnostic inclusion criteria on prevalence and population characteristics across such groups. Methods: Administrative data for 2003-2010 from the Department of Veterans Affairs were used to calculate prevalence rates and assess effects of varying the diagnostic inclusion criteria on population composition for bipolar disorder, schizophrenia, and posttraumatic stress disorder (PTSD). Specifically, for each diagnosis, mutually exclusive sub-populations were compared on the basis of the following inclusion criteria for a given diagnosis: one treatment encounter, two outpatient encounters or one inpatient encounter, and any two encounters. For bipolar disorder and schizophrenia, effects of excluding individuals who had a competing diagnosis of, respectively, schizophrenia or bipolar disorder in the prior 12 months and since 2002 were also determined. Results: In 2010, moving from the broadest definitions of bipolar disorder (N=120,382), schizophrenia (N=91,977), and PTSD (N=554,028) to the most restrictive definitions reduced prevalence rates by, respectively, 28.7%, 34.9%, and 25.7%, with temporal trends for 2003-2010 paralleling results in 2010. Population composition changes with changing diagnostic inclusion criteria were variable, with predominantly small odds ratios. Conclusions: Population composition was relatively robust across common diagnostic inclusion criteria for each condition. Thus choice of criteria can focus on considerations of diagnostic validity and case-finding needs. Three mechanisms for the impact of diagnostic criteria on population composition in administrative data sets are discussed. C1 [Bauer, Mark S.] Ctr Healthcare Org & Implementat Res, Dept Vet Affairs VA, Jamaica Plain, MA USA. [Bauer, Mark S.; Bajor, Laura] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Lee, Austin] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Miller, Christopher J.] Ctr Healthcare Org & Implementat Res, Jamaica Plain, MA USA. [Bajor, Laura] Ctr Org Leadership & Management Res, London, England. [Miller, Christopher J.; Bajor, Laura] VA Boston Healthcare Syst, Boston, MA USA. [Li, Mingfei] Bentley Univ, Dept Math Sci, Waltham, MA USA. [Penfold, Robert B.] Grp Hlth Res Ins, Dept Hlth Serv Res, Seattle, WA USA. RP Bauer, MS (reprint author), Ctr Healthcare Org & Implementat Res, Dept Vet Affairs VA, Jamaica Plain, MA USA. EM mark.bauer@va.gov FU Health Services Research and Development grant from the Office of Research and Development, Veterans Health Administration, U.S. Department of Veterans Affairs [IIR-10-314] FX This material is based on work supported by Health Services Research and Development grant IIR-10-314 (to Dr. Bauer) from the Office of Research and Development, Veterans Health Administration, U.S. Department of Veterans Affairs. The funding organization provided competitive grant support for these analyses but was not otherwise involved in the design or conduct of the study or review or approval of the manuscript. NR 37 TC 6 Z9 6 U1 4 U2 4 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 FEB PY 2015 VL 66 IS 2 BP 141 EP 148 DI 10.1176/appi.ps.201400115 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE3TC UT WOS:000370552100011 PM 25320943 ER PT J AU Kimerling, R Bastian, LA Bean-Mayberry, BA Bucossi, MM Carney, DV Goldstein, KM Phibbs, CS Pomernacki, A Sadler, AG Yano, EM Frayne, SM AF Kimerling, Rachel Bastian, Lori A. Bean-Mayberry, Bevanne A. Bucossi, Meggan M. Carney, Diane V. Goldstein, Karen M. Phibbs, Ciaran S. Pomernacki, Alyssa Sadler, Anne G. Yano, Elizabeth M. Frayne, Susan M. TI Patient-Centered Mental Health Care for Female Veterans SO PSYCHIATRIC SERVICES LA English DT Article ID COLLABORATIVE CARE; WOMEN VETERANS; DEPRESSION; VALIDATION; DISORDERS; SERVICES; QUALITY; VA; INTERVENTIONS; QUESTIONNAIRE AB Objective: Mental health services for women vary widely across the Veterans Health Administration (VHA) system, without consensus on the need for, or organization of, specialized services for women. Understanding women's needs and priorities is essential to guide the implementation of patient-centered behavioral health services. Methods: In a cross-sectional, multisite survey of female veterans using primary care, potential stakeholders were identified for VHA mental health services by assessing perceived or observed need for mental health services. These stakeholders (N=484) ranked priorities for mental health care among a wide range of possible services. The investigators then quantified the importance of having designated women's mental health services for each of the mental health services that emerged as key priorities. Results: Treatment for depression, pain management, coping with chronic general medical conditions, sleep problems, weight management, and posttraumatic stress disorder (PTSD) emerged as women's key priorities. Having mental health services specialized for women was rated as extremely important to substantial proportions of women for each of the six prioritized services. Preference for primary care colocation was strongly associated with higher importance ratings for designated women's mental health services. For specific types of services, race, ethnicity, sexual orientation, PTSD symptoms, and psychiatric comorbidity were also associated with higher importance ratings for designated women's services. Conclusions: Female veterans are a diverse population whose needs and preferences for mental health services vary along demographic and clinical factors. These stakeholder perspectives can help prioritize structural and clinical aspects of designated women's mental health care in the VHA. C1 [Kimerling, Rachel] Vet Affairs VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA. [Kimerling, Rachel; Bucossi, Meggan M.; Carney, Diane V.; Pomernacki, Alyssa; Frayne, Susan M.] Vet Affairs VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA. [Frayne, Susan M.] Stanford Univ, Sch Med, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Bastian, Lori A.] VA Connecticut Healthcare Syst, Hlth Serv Res & Dev HSR&D Pain Res Informat Multi, West Haven, CT USA. [Bastian, Lori A.] Univ Connecticut, Ctr Hlth, Div Gen Internal Med, Farmington, CT USA. [Bean-Mayberry, Bevanne A.] VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Study Healthcare Innovat Implementat &, Sepulveda, CA USA. [Bean-Mayberry, Bevanne A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Health, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA. [Goldstein, Karen M.] Durham VA Med Ctr, HSR&D Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Goldstein, Karen M.] Duke Univ, Dept Med, Durham, NC USA. [Phibbs, Ciaran S.] VA Palo Alto Hlth Care Syst, HSR&D Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Phibbs, Ciaran S.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Sadler, Anne G.] Iowa City VA Hlth Care Syst, HSR&D Ctr Comprehens Access & Delivery Res & Eval, Iowa City, IA USA. [Sadler, Anne G.] Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. RP Kimerling, R (reprint author), Vet Affairs VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA. EM rachel.kimerling@va.gov OI Kimerling, Rachel/0000-0003-0996-4212 FU VA HSRD grant [SDR 10-012] FX This study was funded by VA HSR&D grant SDR 10-012 (Women's Health Research Network). The authors thank Joanne Pavao, M.P.H., Deborah Nazarian, Ph.D., Shannan Sonnicksen, L.C.S.W., M.P.H., Caitlin McLean, M.S., and Julia Lin, Ph.D., of the VA Palo Alto Health Care System; Jill Blakeney, R.N., of Durham VA Medical Center; Ruth Klap, Ph.D., and Julia Yosef, M.S., R.N., of VA Greater Los Angeles Healthcare System; and Brittany D. Martin, M.A., M. Litt., and Holly J. Erschens, B.A., of Iowa City VA 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 VA or the U.S. government. NR 41 TC 6 Z9 6 U1 1 U2 4 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 FEB PY 2015 VL 66 IS 2 BP 155 EP 162 DI 10.1176/appi.ps.201300551 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE3TC UT WOS:000370552100013 PM 25642611 ER PT J AU Fong, ZV Fernandez-del Castillo, C AF Fong, Zhi Ven Fernandez-del Castillo, Carlos TI Intraductal Papillary Mucinous Adenocarcinoma of the Pancreas: Clinical Outcomes, Prognostic Factors, and the Role of Adjuvant Therapy SO VISZERALMEDIZIN LA English DT Review DE Intraductal papillary mucinous adenocarcinoma; Prognostic factors; Adjuvant therapy ID SINGLE-INSTITUTION EXPERIENCE; DUCTAL-ADENOCARCINOMA; SURGICAL RESECTION; CLINICOPATHOLOGICAL CHARACTERISTICS; 1423 PANCREATICODUODENECTOMIES; SYMPTOMATIC PATIENTS; INVASIVE-CARCINOMA; UPDATED EXPERIENCE; PREDICTIVE-FACTORS; NEOPLASM AB Background: Intraductal papillary mucinous adenocarcinoma (IPMCs) occur more frequently in main-duct intraductal papillary mucinous neoplasms. Methods: Review of the literature. Results: The prognosis of IPMCs depends on its histopathological subtype: colloid IPMCs have superior survival rates mainly secondary to more favorable pathological features, whereas tubular IPMCs have survival outcomes similar to that of conventional pancreatic adenocarcinomas. The epithelial background plays an equally important role in defining the biology of IPMCs: gastric IPMC subtypes demonstrate an overall worse survival outcome when compared to intestinal, pancreatobiliary, and oncocytic subtypes. Lymph node involvement is one of the strongest predictors of survival in IPMC, with a decreasing overall survival as the lymph node ratio increases. There is little evidence to support adjuvant chemoradiation in patients with IPMC. Conclusion: Our current understanding of IPMC biology based on histopathological and epithelial background subtypes as well as clinicopathological predictors should influence patient counseling and selection for adjuvant therapy. C1 [Fong, Zhi Ven; Fernandez-del Castillo, Carlos] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org NR 38 TC 2 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-6664 EI 1662-6672 J9 VISZERALMEDIZIN JI Viszeralmedizin PD FEB PY 2015 VL 31 IS 1 BP 43 EP 46 DI 10.1159/000373912 PG 4 WC Surgery SC Surgery GA DH8BO UT WOS:000373018500007 PM 26288615 ER PT J AU Treadway, MT Waskom, ML Dillon, DG Holmes, AJ Park, MTM Chakravarty, MM Dutra, SJ Polli, FE Iosifescu, DV Fava, M Gabrieli, JDE Pizzagalli, DA AF Treadway, Michael T. Waskom, Michael L. Dillon, Daniel G. Holmes, Avram J. Park, Min Tae M. Chakravarty, M. Mallar Dutra, Sunny J. Polli, Frida E. Iosifescu, Dan V. Fava, Maurizio Gabrieli, John D. E. Pizzagalli, Diego A. TI Illness Progression, Recent Stress, and Morphometry of Hippocampal Subfields and Medial Prefrontal Cortex in Major Depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Dentate gyrus; Hippocampus; MAGeT brain; Major depression; mPFC; MRI ID ANTERIOR CINGULATE CORTEX; CORTICAL SURFACE; DENDRITIC MORPHOLOGY; MEMORY IMPAIRMENT; BIPOLAR-DISORDER; DECISION-MAKING; BRAIN; VOLUME; AMYGDALA; SEGMENTATION AB BACKGROUND: Longitudinal studies of illness progression in patients with major depressive disorder (MDD) indicate that the onset of subsequent depressive episodes becomes increasingly decoupled from external stressors. A possible mechanism underlying this phenomenon is that multiple episodes induce long-lasting neurobiological changes that confer increased risk for recurrence. Prior morphometric studies have frequently reported volumetric reductions in patients with MDD-especially in medial prefrontal cortex (mPFC) and the hippocampus-but few studies have investigated whether these changes are exacerbated by prior episodes. METHODS: In a sample of 103 medication-free patients with depression and control subjects with no history of depression, structural magnetic resonance imaging was performed to examine relationships between number of prior episodes, current stress, hippocampal subfield volume and cortical thickness. Volumetric analyses of the hippocampus were performed using a recently validated subfield segmentation approach, and cortical thickness estimates were obtained using vertex-based methods. Participants were grouped on the basis of the number of prior depressive episodes and current depressive diagnosis. RESULTS: Number of prior episodes was associated with both lower reported stress levels and reduced volume in the dentate gyrus. Cortical thinning of the left mPFC was associated with a greater number of prior depressive episodes but not current depressive diagnosis. CONCLUSIONS: Collectively, these findings are consistent with preclinical models suggesting that the dentate gyrus and mPFC are especially vulnerable to stress exposure and provide evidence for morphometric changes that are consistent with stress-sensitization models of recurrence in MDD. C1 [Treadway, Michael T.; Dillon, Daniel G.; Pizzagalli, Diego A.] Harvard Univ, McLean Hosp, Sch Med, Ctr Depress Anxiety & Stress Res, Belmont, MA USA. [Waskom, Michael L.] Stanford Univ, Dept Psychol, Palo Alto, CA 94304 USA. [Holmes, Avram J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Holmes, Avram J.; Dutra, Sunny J.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Park, Min Tae M.; Chakravarty, M. Mallar] Ctr Addict & Mental Hlth, Kimel Family Imaging Genet Lab, Toronto, ON, Canada. [Chakravarty, M. Mallar] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Chakravarty, M. Mallar] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON, Canada. [Polli, Frida E.; Gabrieli, John D. E.] MIT, Cambridge, MA 02139 USA. [Iosifescu, Dan V.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. RP Pizzagalli, DA (reprint author), McLean Hosp, Ctr Depress Anxiety & Stress Res, 115 Mill St, Belmont, MA 02478 USA. EM dap@mclean.harvard.edu OI Dillon, Daniel/0000-0002-1977-700X FU National Institute of Mental Health (NIMH) [R01 MH068376]; National Center for Complementary and Alternative Medicine (NCCAM) [R21 AT002974]; NCCAM [R01 AT001638]; NIMH [K01 MH099232, K99 MH094438]; W. Garfield Weston Foundation; Icahn School of Medicine at Mount Sinai from AstraZeneca; Brainsway; Euthymics Bioscience, Inc.; NeoSync; Roche; Shire; Avanir Pharmaceuticals; CNS Response, Inc.; Otsuka; Servier; Sunovion; Abbott Laboratories; Alkermes, Inc.; American Cyanamid; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells, Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clintara LLC; Covance; Covidien; Eli Lilly; Company; EnVivo Pharmaceuticals Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Harvard Clinical Research Institute; Hoffmann-La Roche; 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 and Depression; National Center for Complementary and Alternative Medicine; National Institute of Drug Abuse; National Institute of Mental Health, Neuralstem, Inc.; Novartis AG; Organon Pharmaceuticals; Pamlab LLC; Pfizer, Inc.; Pharmacia-Upjohn; Pharmaceutical Research Associates, Inc.; Pharmavite LLC; PharmoRx Therapeutics; Photothera; RCT Logic LLC; Sanofi; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories; Affectis Pharmaceuticals AG; Amarin Pharma, Inc.; Auspex Pharmaceuticals; Bayer; Best Practice Project Management, Inc.; BioMarin Pharmaceutical, Inc.; Biovail Corporation; Cephalon, Inc.; Cerecor; Clinical Trials Solutions; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences Pvt Ltd.; Dainippon Sumitomo Pharma Co., Inc.; DOV Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai, Inc.; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Genomind LLC; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research & Development LLC; Knoll Pharmaceuticals Corp.; Labopharm, Inc.; Lundbeck, Inc.; MedAvante Inc.; Merck Co., Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; Neuralstem, Inc.; Neuronetics, Inc.; NextWave Pharmaceuticals; Nutrition 21; Orexigen Therapeutics, Inc.; Otsuka Pharmaceuticals; PharmaStar; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Sepracor, Inc.; Servier Laboratories; Schering-Plough Corporation; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; Tal Medical, Inc.; Tetragenex Pharmaceuticals, Inc.; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; Vanda Pharmaceuticals, Inc.; Advanced Neuro Technology North America; Ono Pharma USA; Pfizer FX This study was supported by National Institute of Mental Health (NIMH) Grant R01 MH068376 awarded to DAP as well as National Center for Complementary and Alternative Medicine (NCCAM) Grant R21 AT002974 awarded to DAP and NCCAM R01 AT001638 awarded to MF. AJH and DGD were supported by NIMH Grants K01 MH099232 and K99 MH094438, respectively. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. MMC was supported by the W. Garfield Weston Foundation.; DVI has received over the past 3 years funding through Icahn School of Medicine at Mount Sinai from AstraZeneca, Brainsway, Euthymics Bioscience, Inc., NeoSync, Roche, and Shire and consulting fees from Avanir Pharmaceuticals, CNS Response, Inc., Otsuka, Servier, and Sunovion.; MF has received research support from Abbott Laboratories, Alkermes, Inc., American Cyanamid, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, 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, Hoffmann-La Roche, 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 and Depression, National Center for Complementary and Alternative Medicine, National Institute of Drug Abuse, National Institute of Mental Health, Neuralstem, Inc., Novartis AG, Organon Pharmaceuticals, Pamlab LLC, Pfizer, Inc., Pharmacia-Upjohn, Pharmaceutical Research Associates, Inc., Pharmavite LLC, PharmoRx Therapeutics, Photothera, Roche, RCT Logic LLC (formerly Clinical Trials Solutions LLC), Sanofi, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, Wyeth-Ayerst Laboratories; advisory/consulting fees from Abbott Laboratories, Affectis Pharmaceuticals AG, Alkermes, Inc., Amarin Pharma, Inc., Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer, Best Practice Project Management, Inc., BioMarin Pharmaceutical, Inc., Biovail Corporation, BrainCells, Inc., Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Inc., Cerecor, Clinical Trials Solutions, CNS Response, Inc., Compellis Pharmaceuticals, Cypress Pharmaceutical, Inc., DiagnoSearch Life Sciences Pvt Ltd., Dainippon 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., Rexahn Pharmaceuticals, Inc., Ridge Diagnostics, Inc., Roche, Sanofi, Sepracor, Inc., Servier Laboratories, Schering-Plough Corporation, Solvay Pharmaceuticals, Inc., Somaxon Pharmaceuticals, Inc., Somerset Pharmaceuticals, Sunovion Pharmaceuticals, Supernus Pharmaceuticals, Inc., Synthelabo, Takeda Pharmaceutical Company Limited, Tal Medical, Inc., Tetragenex Pharmaceuticals, Inc., TransForm Pharmaceuticals, Inc., Transcept Pharmaceuticals, Inc., and Vanda Pharmaceuticals, Inc.; and speaking/publishing royalties from AdaMed, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim GmbH, BristolMyers 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., and Wyeth-Ayerst Laboratories. MF has equity holdings in Compellis Pharmaceuticals and PsyBrain, Inc. and receives royalty/patent or other income from patent for Sequential Parallel Comparison Design, which is licensed by Massachusetts General Hospital to RCT Logic LLC. He has a patent application for a combination of scopolamine and ketamine in major depressive disorder and holds a copyright for the Massachusetts General Hospital Cognitive & Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs & Symptoms, and SAFER, Lippincott Williams & Wilkins, Wolters Kluwer, World Scientific Publishing Co. Pte. Ltd.; DAP has received over the past 3 years honoraria or consulting fees from Advanced Neuro Technology North America, AstraZeneca, Ono Pharma USA, Pfizer, Servier, and Shire for activities unrelated to this project. NR 78 TC 38 Z9 41 U1 3 U2 27 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 FEB 1 PY 2015 VL 77 IS 3 BP 285 EP 294 DI 10.1016/j.biopsych.2014.06.018 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AX3NG UT WOS:000346845500017 PM 25109665 ER PT J AU Mayeda, ER Whitmer, RA Yaffe, K AF Mayeda, Elizabeth Rose Whitmer, Rachel A. Yaffe, Kristine TI Diabetes and Cognition SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Type 2 diabetes; Cognition; Cognitive decline; Dementia; Aging; Epidemiology ID VASCULAR RISK-FACTORS; ALZHEIMERS-DISEASE; DEMENTIA RISK; OLDER PERSONS; SEVERE HYPOGLYCEMIA; OXIDATIVE DAMAGE; FOLLOW-UP; LATE-LIFE; MELLITUS; DECLINE AB Dementia is a major cause of disability and death among older adults. Those with type 2 diabetes (T2D) are 50-100% more likely to develop dementia than those without T2D, but it is unknown whether this association reflects a causal relationship. Proposed mechanisms through which T2D could cause dementia include the effects of insulin dysregulation and chronic hyperglycemia on features of Alzheimer's disease and macrovascular and microvascular disorders in the brain. More research is needed to elucidate the link between T2D and dementia and identify strategies to maintain cognitive function among people with T2D. C1 [Mayeda, Elizabeth Rose] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. [Whitmer, Rachel A.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Mayeda, ER (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM elizabeth.mayeda@ucsf.edu FU National Institute on Aging grant [K24 AG031155]; National Institute of Diabetes and Digestive and Kidney Diseases grant [R01DK081796]; BrightFocus Foundation FX The authors were supported by funding from National Institute on Aging grant K24 AG031155, National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK081796, and grant support from the BrightFocus Foundation. NR 92 TC 15 Z9 16 U1 0 U2 24 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD FEB PY 2015 VL 31 IS 1 BP 101 EP + DI 10.1016/j.cger.2014.08.021 PG 16 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AX1CX UT WOS:000346686900010 PM 25453304 ER PT J AU Agaram, NP Chen, HW Zhang, L Sung, YS Panicek, D Healey, JH Nielsen, GP Fletcher, CDM Antonescu, CR AF Agaram, Narasimhan P. Chen, Hsiao-Wei Zhang, Lei Sung, Yun-Shao Panicek, David Healey, John H. Nielsen, G. Petur Fletcher, Christopher D. M. Antonescu, Cristina R. TI EWSR1-PBX3: A Novel Gene Fusion in Myoepithelial Tumors SO GENES CHROMOSOMES & CANCER LA English DT Article ID SOFT-TISSUE; MALIGNANT MYOEPITHELIOMA; MODULAR FRAMEWORK; PRE-B; BONE; RNA; REARRANGEMENTS; ORGANOGENESIS; EXPRESSION; CARCINOMA AB The genetics of myoepithelial tumors (ME) of soft tissue and bone have recently been investigated, with EWSR1-related gene fusions being seen in approximately half of the tumors. The fusion partners of EWSR1 so far described include POU5F1, PBX1, ZNF444 and, in a rare case, ATF1. We investigated by RNA sequencing an index case of EWSR1-rearranged ME of the tibia, lacking a known fusion partner, and identified a novel EWSR1-PBX3 fusion. The fusion was further validated by reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization (FISH). To evaluate if this is a recurrent event, an additional cohort of 22 EWSR1-rearranged ME cases lacking a fusion partner were screened by FISH for abnormalities in PBX3 gene. Thus, two additional cases were identified showing an EWSR1-PBX3 gene fusion. One of them was also intraosseous involving the ankle, while the other occurred in the soft tissue of the index finger. The morphology of the EWSR1-PBX3 fusion positive cases showed similar findings, with nests or sheets of epithelioid to spindle cells in a partially myxoid to collagenous matrix. All three cases showed expression of S100 and EMA by immunohistochemistry. In summary, we report a novel EWSR1-PBX3 gene fusion in a small subset of ME, thereby expanding the spectrum of EWSR1-related gene fusions seen in these tumors. This gene fusion seems to occur preferentially in skeletal ME, with two of the three study cases occurring in intraosseous locations. (c) 2014 Wiley Periodicals, Inc. C1 [Agaram, Narasimhan P.; Chen, Hsiao-Wei; Zhang, Lei; Sung, Yun-Shao; Antonescu, Cristina R.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Panicek, David] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Healey, John H.] Mem Sloan Kettering Canc Ctr, Dept Surg, Orthoped Serv, New York, NY 10065 USA. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fletcher, Christopher D. M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Agaram, NP (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA. EM agaramn@mskcc.org; antonesc@mskcc.org OI Panicek, David/0000-0003-0302-174X FU Cycle for Survival [P01CA47179, P50 CA 140146-01] FX Supported by: Cycle for Survival (C.R.A.) Grant Numbers: P01CA47179 (CRA), P50 CA 140146-01 (CRA). NR 33 TC 14 Z9 14 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-2257 EI 1098-2264 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD FEB PY 2015 VL 54 IS 2 BP 63 EP 71 DI 10.1002/gcc.22216 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA AW5ZE UT WOS:000346348600001 PM 25231231 ER PT J AU Naraghi, L Peev, MP Esteve, R Chang, YC Berger, DL Thayer, SP Rattner, DW Lillemoe, KD Kaafarani, H Yeh, DD de Moya, MA Fagenholz, PJ Velmahos, GS King, DR AF Naraghi, Leily Peev, Miroslav P. Esteve, Rogette Chang, Yuchiao Berger, David L. Thayer, Sarah P. Rattner, David W. Lillemoe, Keith D. Kaafarani, Haytham Yeh, Daniel D. de Moya, Marc A. Fagenholz, Peter J. Velmahos, George S. King, David R. TI The influence of anesthesia on heart rate complexity during elective and urgent surgery in 128 patients SO JOURNAL OF CRITICAL CARE LA English DT Article DE Entropy; Surgery; SampEn; Elective; Variability; Complexity ID DIMINISHED PHYSIOLOGICAL RESERVE; BEDSIDE MONITORING STRATEGY; 1,425 TRAUMA PATIENTS; RATE-VARIABILITY; LIFESAVING INTERVENTIONS; GENERAL-ANESTHESIA; PREDICTS; MORTALITY; TOOL; VOLATILITY AB Background: As an emerging "new vital sign," heart rate complexity (by sample entropy [SampEn]) has been shown to be a useful trauma triage tool by predicting occult physiologic compromise and need for life-saving interventions. Sample entropy may be confounded by anesthesia possibly limiting its value intraoperatively. We investigated the effects of anesthesia on SampEn during elective and urgent surgical procedures. We hypothesized that SampEn is reduced by general anesthesia. Methods: With institutional review board-approved waiver of informed consent, 128 patients undergoing elective or urgent general surgery were prospectively enrolled. Real-time heart rate complexity was calculated using SampEn through electrocardiogram recordings of 200 consecutive beats in a continuous sliding-window fashion. We recorded SampEn starting 10 minutes before induction until 10 minutes after emergence from anesthesia. The time before induction of anesthesia was categorized as period 1, the time after induction and before emergence as period 2 (intraoperative), and the time after emergence as period 3. We analyzed SampEn changes as patients moved between the different periods and made 3 comparisons: from period 1 with period 2 (comparison A), from period 2 with period 3 (comparison B). We also compared period 1 with period 3 SampEn (comparison C). Results: The mean SampEn value for all patients before induction of anesthesia was 1.55 +/- 0.58. In each 1 of the 3, comparisons there was a decline in SampEn. Comparison A had a mean decrease of 0.53 +/- 0.55 (P < .0001), comparison B had a decrease of 0.13 +/- 0.52 (P < .0051), and the mean SampEn difference for comparison C was 0.66 +/- 0.53 (P < .0001). Certain pharmacologics had significant effect on SampEn as did need for urgent surgery and American Society of Anesthesiologists class. Conclusion: Sample entropy decreases after induction of anesthesia and continues to decrease even immediately after emergence in patients without any immediately life-threatening conditions. This finding may complicate interpretation low complexity as a predictor of life-saving interventions in patients in the perioperative period. (C) 2014 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM dking3@partners.org OI King, David/0000-0003-1028-1478 NR 29 TC 0 Z9 0 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD FEB PY 2015 VL 30 IS 1 BP 145 EP 149 DI 10.1016/j.jcrc.2014.08.008 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA AW4GJ UT WOS:000346238900025 PM 25239820 ER PT J AU Courtwright, AM Brackett, S Cadge, W Krakauer, EL Robinson, EM AF Courtwright, Andrew M. Brackett, Sharon Cadge, Wendy Krakauer, Eric L. Robinson, Ellen M. TI Experience with a hospital policy on not offering cardiopulmonary resuscitation when believed more harmful than beneficial SO JOURNAL OF CRITICAL CARE LA English DT Article DE Cardiopulmonary resuscitation; Do not resuscitate; End of life; Ethics consultation; Medical ethics; Medical futility ID OF-LIFE CARE; MEDICAL FUTILITY; INTENSIVE-CARE; END; DECISIONS; ORDERS; CONSENT; STATES; UNITS; CPR AB Purpose: This study investigated the impact of age, race, and functional status on decisions not to offer cardiopulmonary resuscitation (CPR) despite patient or surrogate requests that CPR be performed. Methods: This was a retrospective cohort study of all ethics committee consultations between 2007 and 2013 at a large academic hospital with a not offering CPR policy. Results: There were 134 cases of disagreement over whether to provide CPR. In 45 cases (33.6%), the patient or surrogate agreed to a do-not-resuscitate (DNR) order after initial ethics consultation. In 67 (75.3%) of the remaining 89 cases, the ethics committee recommended not offering CPR. In the other 22 (24.7%) cases, the ethics committee recommended offering CPR. There was no significant relationship between age, race, or functional status and the recommendation not to offer CPR. Patients who were not offered CPR were more likely to be critically ill (61.2% vs 18.2%, P < .001). The 90-day mortality rate among patients who were not offered CPR was 90.2%. Conclusions: There was no association between age, race, or functional status and the decision not to offer CPR made in consultation with an ethics committee. Orders to withhold CPR were more common among critically ill patients. (C) 2014 Elsevier Inc. All rights reserved. C1 [Courtwright, Andrew M.; Robinson, Ellen M.] Massachusetts Gen Hosp, Inst Patient Care, Patient Care Serv, Boston, MA 02114 USA. [Courtwright, Andrew M.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Brackett, Sharon] Massachusetts Gen Hosp, Ellison Surg Intens Care Unit 4, Patient Care Serv, Boston, MA 02114 USA. [Cadge, Wendy] Brandeis Univ, Dept Sociol, Waltham, MA USA. [Krakauer, Eric L.] Massachusetts Gen Hosp, Div Palliat Care, Boston, MA 02114 USA. [Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Robinson, Ellen M.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Courtwright, AM (reprint author), Ctr Chest Dis, 15 Francis St, Boston, MA 02115 USA. EM acourtwright@partners.org FU Yvonne L. Munn Post Doctoral Research Fellowship; Yvonne L. Munn Center for Nursing Research, Institute for Patient Care, MGH FX Research support for E.R. was provided by the Yvonne L. Munn Post Doctoral Research Fellowship and the Yvonne L. Munn Center for Nursing Research, Institute for Patient Care, MGH. NR 34 TC 5 Z9 6 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD FEB PY 2015 VL 30 IS 1 BP 173 EP 177 DI 10.1016/j.jcrc.2014.10.003 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA AW4GJ UT WOS:000346238900030 PM 25457115 ER PT J AU Kwok, AC Hu, YY Dodgion, CM Jiang, W Ting, GV Taback, N Lipsitz, SR Weeks, JC Greenberg, CC AF Kwok, Alvin C. Hu, Yue-Yung Dodgion, Christopher M. Jiang, Wei Ting, Gladys V. Taback, Nathan Lipsitz, Stuart R. Weeks, Jane C. Greenberg, Caprice C. TI Invasive procedures in the elderly after stage IV cancer diagnosis SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Stage IV cancer; End-of-life; Procedure utilization ID OF-LIFE DISCUSSIONS; CELL LUNG-CANCER; UNITED-STATES; CARE; END; TRENDS; COST; SURVIVAL; EPIDEMIOLOGY; SURVEILLANCE AB Background: Invasive procedures are resource intense and may be associated with substantial morbidity. These harms must be carefully balanced with the benefits gained in life expectancy and quality of life. Prior research has demonstrated an increasing aggressiveness of care in cancer patients at the end-of-life. To better characterize surgical care in this setting, we sought to examine trends in the use of invasive procedures in patients diagnosed with metastatic cancer on presentation. Materials and methods: Using Surveillance Epidemiology and End Results -Medicare data, we identified invasive procedure claims from 1994-2009 for patients diagnosed with incident stage IV breast, colorectal, lung, and prostate cancer patients in 1995-2006. We grouped procedures into surgically relevant categories, using an adaptation of the Clinical Classifications Software, and measured utilization and relative changes over time. Results: Of stage IV patients diagnosed in 2002-2006, 96% underwent a procedure during the course of their cancer care including 63% after the diagnostic period, and 25% in the last month of life. Between 1996 and 2006, minimal change was observed in utilization during the diagnostic period (+1.5%). However, there were significant increases during continuing care (+20.7%) and the last month of life (+21.5%). Procedures consistent with primary tumor resection decreased, whereas those with probable palliative intent and those unrelated to cancer increased. Conclusions: Nearly all patients who present with metastatic cancer undergo invasive procedures. Although overall utilization is increasing, the specific procedure types indicate that it may be appropriate, enhancing the quality of life in this vulnerable population. (C) 2015 Elsevier Inc. All rights reserved. C1 [Kwok, Alvin C.; Hu, Yue-Yung; Dodgion, Christopher M.; Jiang, Wei; Lipsitz, Stuart R.; Greenberg, Caprice C.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Kwok, Alvin C.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Kwok, Alvin C.] Univ Utah, Sch Med, Dept Plast & Reconstruct Surg, Salt Lake City, UT USA. [Hu, Yue-Yung] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Dodgion, Christopher M.; Greenberg, Caprice C.] Univ Wisconsin Hosp & Clin, Dept Surg, Wisconsin Surg Outcomes Res WiSOR Program, Madison, WI 53792 USA. [Ting, Gladys V.; Taback, Nathan; Weeks, Jane C.; Greenberg, Caprice C.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Hu, YY (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, 110 Francis St,Suite 9B, Boston, MA 02215 USA. EM yhu@bidmc.harvard.edu RI JIANG, WEI /F-3930-2015; Dodgion, Chris/A-2877-2016 OI Dodgion, Chris/0000-0002-5789-7731 FU National Institutes of Health [RC2CA148185-01, 2T32DK00754-12, L30RR031458-01, L30CA123695-03] FX This project was funded by the National Institutes of Health grants #RC2CA148185-01 (J.C.W. and C.C.G.), #2T32DK00754-12 (Y.-Y.H.), #L30RR031458-01 (Y.-Y.H.), and #L30CA123695-03 (C.C.G.). NR 30 TC 4 Z9 4 U1 1 U2 15 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 FEB PY 2015 VL 193 IS 2 BP 754 EP 763 DI 10.1016/j.jss.2014.08.021 PG 10 WC Surgery SC Surgery GA AW4IK UT WOS:000346244300033 PM 25234747 ER PT J AU Hobai, IA Morse, JC Siwik, DA Colucci, WS AF Hobai, Ion A. Morse, Justin C. Siwik, Deborah A. Colucci, Wilson S. TI Lipopolysaccharide and cytokines inhibit rat cardiomyocyte contractility in vitro SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Sepsis; Sepsis-induced cardiomyopathy; Calcium; Excitation-contraction coupling; L-type calcium channel; SERCA; Na+/Ca2+ exchange ID NITRIC-OXIDE SYNTHASE; CARDIAC SARCOPLASMIC-RETICULUM; NECROSIS-FACTOR-ALPHA; VENTRICULAR MYOCYTES; CA2+ TRANSIENTS; SEPTIC SHOCK; MYOCARDIAL DYSFUNCTION; INDUCED DEPRESSION; CALCIUM CURRENT; HEART-FAILURE AB Background: Sepsis-induced cardiomyopathy (SIC) is thought to be the result of detrimental effects of inflammatory mediators on the cardiac muscle. Here we studied the effects of prolonged (24 +/- 4 h) exposure of adult rat ventricular myocytes (ARVM) to bacterial lipopolysaccharide (LPS) and inflammatory cytokines tumor necrosis factor (TNF) and interleukins-1 (IL-1) and IL-6. Materials and methods: We measured sarcomere shortening (SS) and cellular calcium (Ca2+) transients (Delta Ca-i, with fura-2 AM) in isolated cardiomyocytes externally paced at 5 Hz at 37 degrees C. Results: SS decreased after incubation with LPS (100 mu g/mL), IL-1 (100 ng/mL), and IL-6 (30 ng/mL), but not with lesser doses of these mediators, or TNF (10-100 ng/mL). A combination of LPS (100 mu g/mL), TNF, IL-1, and IL-6 (each 100 ng/mL; i.e., "Cytomix-100") induced a maximal decrease in SS and Delta Ca-i. Sarcoplasmic reticulum (SR) Ca2+ load (Ca-SR, measured with caffeine) was unchanged by Cytomix-100; however, SR fractional release (Delta Ca-i/Ca-SR) was decreased. Underlying these effects, Ca2+ influx into the cell (via L-type Ca2+ channels, LTCC) and Ca2+ extrusion via Na2+/Ca2+ exchange were decreased by Cytomix-100. SR Ca2+ pump (SERCA) (SR Ca2+ ATPase) was not affected. Conclusions: Prolonged exposure of ARVM to a mixture of LPS and inflammatory cytokines inhibits cell contractility. The effect is mediated by the inhibition of Ca2+ influx via LTCC, and partially opposed by the inhibition of Na+/Ca2+ exchange. Because both mechanisms are commonly seen in animal models of SIC, we conclude that prolonged challenge with Cytomix-100 of ARVM may represent an accurate in vitro model for SIC. (C) 2015 Elsevier Inc. All rights reserved. C1 [Hobai, Ion A.; Morse, Justin C.; Siwik, Deborah A.; Colucci, Wilson S.] Boston Univ, Med Ctr, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA. [Hobai, Ion A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Hobai, IA (reprint author), Boston Univ, Med Ctr, Dept Med, Cardiovasc Med Sect, Evans Basic Res Bldg,650 Albany St,X740, Boston, MA 02118 USA. EM ihobai@partners.org FU National Institutes of Health [HL-061639, HL-064750]; National Heart, Lung, and Blood Institute - Boston University Cardiovascular Proteomics Center [N01-HV-28178]; National Institute of General Medical Sciences [K08GM096082, T32GM00 7592]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX This work was supported by National Institutes of Health grants HL-061639, HL-064750 (W.S.C.) and the National Heart, Lung, and Blood Institute -sponsored Boston University Cardiovascular Proteomics Center (Contract No. N01-HV-28178, W.S.C.). I.A.H. acknowledges support from K08GM096082 and T32GM00 7592 (National Institute of General Medical Sciences) and the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. Other support includes Boston University Student Research Awards for J.C.M. NR 49 TC 4 Z9 4 U1 0 U2 16 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 FEB PY 2015 VL 193 IS 2 BP 888 EP 901 DI 10.1016/j.jss.2014.09.015 PG 14 WC Surgery SC Surgery GA AW4IK UT WOS:000346244300049 PM 25439505 ER PT J AU Richard, MLL Nowling, TK Brandon, D Watson, DK Zhang, XK AF Richard, Mara L. Lennard Nowling, Tamara K. Brandon, Danielle Watson, Dennis K. Zhang, Xian K. TI Fli-1 controls transcription from the MCP-1 gene promoter, which may provide a novel mechanism for chemokine and cytokine activation SO MOLECULAR IMMUNOLOGY LA English DT Article DE Transcriptional factors; Gene regulation; Chemokines; Inflammation; Fli-1; MCP-1 ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; SYSTEMIC-LUPUS-ERYTHEMATOSUS; NF-KAPPA-B; ETS FAMILY; RENAL-DISEASE; GROWTH-FACTOR; T-CELLS; EXPRESSION; BINDING; MICE AB Regulation of proinflammatory cytokines and chemokines is a primary role of the innate immune response. MCP-1 is a chemokine that recruits immune cells to sites of inflammation. Expression of MCP-1 is reduced in primary kidney endothelial cells from mice with a heterozygous knockout of the Fli-1 transcription factor. Fli-1 is a member of the Ets family of transcription factors, which are evolutionarily conserved across several organisms including Drosophilla, Xenopus, mouse and human. Ets family members bind DNA through a consensus sequence GGAA/T, or Ets binding site (EBS). Fli-1 binds to EBSs within the endogenous MCP-1 promoter by ChIP assay. In this study, transient transfection assays indicate that the Fli-1 gene actively promotes transcription from the MCP-1 gene promoter in a dose-dependent manner. Mutation of the DNA binding domain of Fli-1 demonstrated that Fli-1 activates transcription of MCP-1 both directly, by binding to the promoter, and indirectly, likely through interactions with other transcription factors. Another-Ets-transcription-factor, Ets-1, was also tested, but failed to promote transcription. While Ets-1 failed to drive transcription independently, a weak synergistic activation of the MCP-1 promoter was observed between Ets-1 and FR-1. In addition, Fli-1 and the NF kappa B family member p65 were found to interact synergistically to activate transcription from the MCP-1 promoter, while Sp1 and p50 inhibit this interaction. Deletion studies identified that EBSs in the distal and proximal MCP-1 promoter are critical for Fli-1 activation from the MCP-1 promoter. Together, these results demonstrate that Fli-1 is a novel regulator of the proinflammatory chemokine MCP-1, that interacts with other transcription factors to form a complex transcriptional mechanism for the activation of MCP-1 and mediation of the inflammatory response. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Richard, Mara L. Lennard; Nowling, Tamara K.; Brandon, Danielle; Zhang, Xian K.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Nowling, Tamara K.; Zhang, Xian K.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29403 USA. [Watson, Dennis K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Watson, Dennis K.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. RP Zhang, XK (reprint author), Div Rheumatol & Immunol, Suite 912,96 Jonathan Lucas St,MSC637, Charleston, SC 29425 USA. EM zhangjo@musc.edu OI Watson, Dennis/0000-0003-3448-7657 FU National Institute of Health (NIAMS) [AR056670] FX This research study was supported by the National Institute of Health grant (NIAMS, AR056670 to X.K.Z.). We would like to thank Dr. Jeremy Boss from the Emory University School of Medicine for providing us with the pJECAT2.6 vector and the p50, p65 and Sp1 expression constructs. We would also like to thank Dr. Maria Trojanowska from the Boston University School of Medicine Arthritis Center for the Fli-1 DNA binding mutant expression construct. NR 45 TC 3 Z9 3 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD FEB PY 2015 VL 63 IS 2 SI SI BP 566 EP 573 DI 10.1016/j.molimm.2014.07.013 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA AW8WT UT WOS:000346540900053 ER PT J AU Ramly, E Kaafarani, HMA Velmahos, GC AF Ramly, Elie Kaafarani, Haytham M. A. Velmahos, George C. TI The Effect of Aging on Pulmonary Function Implications for Monitoring and Support of the Surgical and Trauma Patient SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Aging; Pulmonary function; Perioperative care; Postoperative pulmonary complications ID COLLEGE-OF-PHYSICIANS; RANDOMIZED CONTROLLED-TRIAL; MULTIFACTORIAL RISK INDEX; POSITIVE AIRWAY PRESSURE; MAJOR NONCARDIAC SURGERY; ABDOMINAL-SURGERY; NONCARDIOTHORACIC SURGERY; POSTOPERATIVE DELIRIUM; ELDERLY-PATIENTS; CONTRACTILE PROPERTIES AB Age-related anatomic, physiologic, and immunologic changes to the pulmonary system, as well as a high prevalence of chronic pulmonary diseases, puts the geriatric patient at an especially high risk for postoperative pulmonary complications. Successful perioperative respiratory care of the geriatric patient relies on careful risk assessment and optimization of pulmonary function and support. The success of such efforts aimed at preventing and/or mitigating pulmonary complications in the geriatric patient depends on a thorough, individualized, yet standardized and evidence-based approach to the care of every patient. C1 [Ramly, Elie; Kaafarani, Haytham M. A.; Velmahos, George C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Kaafarani, HMA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hkaafarani@mgh.harvard.edu NR 103 TC 8 Z9 8 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 2015 VL 95 IS 1 BP 53 EP + DI 10.1016/j.suc.2014.09.009 PG 18 WC Surgery SC Surgery GA AW9AF UT WOS:000346549500007 PM 25459542 ER PT J AU Scandrett, KG Zuckerbraun, BS Peitzman, AB AF Scandrett, Karen G. Zuckerbraun, Brian S. Peitzman, Andrew B. TI Operative Risk Stratification in the Older Adult SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Geriatric; Frailty; Goals of care; Cognitive function ID AMERICAN GERIATRICS SOCIETY; COLLEGE-OF-PHYSICIANS; SERVICES-TASK-FORCE; ELDER LIFE PROGRAM; SURGICAL OUTCOMES; POSTOPERATIVE COMPLICATIONS; NONCARDIOTHORACIC SURGERY; PULMONARY COMPLICATIONS; PREOPERATIVE ASSESSMENT; ASPIRATION PNEUMONIA AB As the population ages, the health care system must to adapt to the needs of the older population. Hospitalization risks are particularly significant in the frail geriatric patients, with costly and morbid consequences. Appropriate preoperative assessment can identify sources of increased risk and enable the surgical team to manage this risk, through "prehabilitation," intraoperative modification, and postoperative care. Geriatric preoperative assessment expands usual risk stratification and careful medication review to include screening for functional disability, cognitive impairment, nutritional deficiency, and frailty. The information gathered can also equip the surgeon to develop a patient-centered and realistic treatment plan. C1 [Scandrett, Karen G.] Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Zuckerbraun, Brian S.; Peitzman, Andrew B.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. RP Peitzman, AB (reprint author), UPMC Presbyterian, Dept Surg, F-1281, Pittsburgh, PA 15213 USA. EM peitzmanab@upmc.edu NR 84 TC 4 Z9 4 U1 6 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 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 2015 VL 95 IS 1 BP 149 EP + DI 10.1016/j.suc.2014.09.014 PG 26 WC Surgery SC Surgery GA AW9AF UT WOS:000346549500014 PM 25459549 ER PT J AU Micheletti, RG Werth, VP AF Micheletti, Robert G. Werth, Victoria P. TI Small Vessel Vasculitis of the Skin SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Small vessel vasculitis of the skin; Cutaneous vasculitis; Leukocytoclastic vasculitis; Hypersensitivity vasculitis; IgA vasculitis; Henoch-Schonlein purpura ID HENOCH-SCHONLEIN PURPURA; CUTANEOUS LEUKOCYTOCLASTIC VASCULITIS; URTICARIAL-VASCULITIS; CLINICAL-FEATURES; HYPERSENSITIVITY VASCULITIS; DIRECT IMMUNOFLUORESCENCE; LUPUS-ERYTHEMATOSUS; ETIOLOGIC FACTORS; CONTROLLED-TRIAL; THERAPY AB Small vessel vasculitis in the skin manifests with palpable purpura on the lower extremities. This clinical presentation prompts a complete physical examination, history, and review of systems, as well as biopsies for routine processing and direct immunofluorescence to confirm the diagnosis. The presence of vasculitis in other organs, associated underlying conditions, and the severity of cutaneous manifestations dictate management. The majority of cases are self-limited, and overall the prognosis is favorable. Still, a subset of patients can have serious complications and chronic or recurrent disease. C1 [Micheletti, Robert G.; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Micheletti, Robert G.; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Dept Dermatol, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA. RP Micheletti, RG (reprint author), Univ Penn, Perelman Sch Med, Dept Dermatol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM Robert.Micheletti@uphs.upenn.edu NR 43 TC 7 Z9 7 U1 2 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-857X EI 1558-3163 J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 2015 VL 41 IS 1 BP 21 EP + DI 10.1016/j.rdc.2014.09.006 PG 13 WC Rheumatology SC Rheumatology GA AW3XS UT WOS:000346217100004 PM 25399937 ER PT J AU Miloslavsky, EM Stone, JH Unizony, SH AF Miloslavsky, Eli M. Stone, John H. Unizony, Sebastian H. TI Challenging Mimickers of Primary Systemic Vasculitis SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Mimicker; Vasculitis; IgG4-related disease; Livedoid vasculopathy; Segmental arterial mediolysis; Lymphomatoid granulomatosis; Fibromuscular dysplasia; Degos disease ID SEGMENTAL ARTERIAL MEDIOLYSIS; MALIGNANT ATROPHIC PAPULOSIS; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; PULMONARY LYMPHOMATOID GRANULOMATOSIS; CEREBRAL VASOCONSTRICTION SYNDROMES; PRIMARY ANTIPHOSPHOLIPID SYNDROME; CALCIFIC UREMIC ARTERIOLOPATHY; DIFFUSE ALVEOLAR HEMORRHAGE; UNITED-STATES REGISTRY; FIBROMUSCULAR DYSPLASIA AB The need to distinguish true primary systemic vasculitis from its multiple potential mimickers is one of the most challenging diagnostic conundrums in clinical medicine. This article reviews 9 challenging vasculitis mimickers: fibromuscular dysplasia, calciphylaxis, segmental arterial mediolysis, anti-phospholipid syndrome, hypereosinophilic syndrome, lymphomatoid granulomatosis, malignant atrophic papulosis, livedoid vasculopathy, and immunoglobulin G4-related disease. C1 [Miloslavsky, Eli M.; Stone, John H.; Unizony, Sebastian H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM jhstone@mgh.harvard.edu NR 113 TC 4 Z9 4 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-857X EI 1558-3163 J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 2015 VL 41 IS 1 BP 141 EP + DI 10.1016/j.rdc.2014.09.011 PG 21 WC Rheumatology SC Rheumatology GA AW3XS UT WOS:000346217100012 PM 25399945 ER PT J AU Psaros, C Barinas, J Robbins, GK Bedoya, CA Park, ER Safren, SA AF Psaros, Christina Barinas, Jennifer Robbins, Gregory K. Bedoya, C. Andres Park, Elyse R. Safren, Steven A. TI Reflections on living with HIV over time: exploring the perspective of HIV-infected women over 50 SO AGING & MENTAL HEALTH LA English DT Article DE women; coping; aging; HIV/AIDS; adjustment ID RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH; OLDER-ADULTS; HIV/AIDS; SUPPORT; RISK; LIFE; INTERVENTION; INDIVIDUALS; OUTCOMES AB Objectives: Approximately 32.7% of people living with HIV/AIDS (PLWHA) in the USA are now over the age of 50. Women comprise a significant percentage of the US HIV epidemic and the percentage of women diagnosed with HIV continues to grow; however, little is known about women's experiences living and coping with HIV over time. The goal of this study was to explore the experiences of US women over 50 living with HIV to better understand how they make sense of their diagnosis and cope with their illness over time and during the aging process. Method: Nineteen women (mean age = 56.79, SD = 4.63) referred from Boston-area organizations and hospitals completed one-time, in-depth individual interviews, out of which 47% of the participants were identified as Black/African Americans, and 37% as White. The average time since diagnosis was 16.32years (SD = 5.70). Inclusion criteria included: (1) female sex, (2) aged 50 or older, (3) HIV diagnosis, and (4) English speaking. Transcribed interviews were analyzed using a grounded theory approach and NVivo 9 software. Results: Findings are described across the following themes: (1) experiences at diagnosis, (2) uncertainty of disease course, (3) acceptance, and (4) living 'well' with HIV. Participants appeared to be well adjusted to their HIV diagnosis and described a progression to acceptance and survivorship; they identified strategies to 'live well' in the context of HIV. For some, health-related uncertainty about the future remained. These findings were organized into a model of coping with HIV. Conclusion: Themes and issues identified by this study may help guide interventions across the lifespan for women with HIV. C1 [Psaros, Christina; Barinas, Jennifer; Bedoya, C. Andres; Park, Elyse R.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Robbins, Gregory K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Psaros, C (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM cpsaros@partners.org FU Harvard University Center for AIDS Research (CFAR), an NIH [P30 AI060354]; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; NCCAM; FIC; OAR; [K23 MH096651] FX Dr Psaros' time was supported by the Harvard University Center for AIDS Research (CFAR), an NIH funded program (P30 AI060354) which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NCCAM, FIC, and OAR, and K23 MH096651. NR 29 TC 2 Z9 2 U1 0 U2 26 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 EI 1364-6915 J9 AGING MENT HEALTH JI Aging Ment. Health PD FEB 1 PY 2015 VL 19 IS 2 BP 121 EP 128 DI 10.1080/13607863.2014.917608 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AU1FB UT WOS:000345365300003 PM 24903460 ER PT J AU Stewart, T Sossi, V Aasly, JO Wszolek, ZK Uitti, RJ Hasegawa, K Yokoyama, T Zabetian, CP Leverenz, JB Stoessl, AJ Wang, Y Ginghina, C Liu, CQ Cain, KC Auinger, P Kang, UJ Jensen, PH Shi, M Zhang, J AF Stewart, Tessandra Sossi, Vesna Aasly, Jan O. Wszolek, Zbigniew K. Uitti, Ryan J. Hasegawa, Kazuko Yokoyama, Teruo Zabetian, Cyrus P. Leverenz, James B. Stoessl, Alexander Jon Wang, Yu Ginghina, Carmen Liu, Changqin Cain, Kevin C. Auinger, Peggy Kang, Un Jung Jensen, Poul Henning Shi, Min Zhang, Jing TI Phosphorylated alpha-synuclein in Parkinson's disease: correlation depends on disease severity SO ACTA NEUROPATHOLOGICA COMMUNICATIONS LA English DT Article DE Parkinson's disease; Cerebrospinal fluid; Biomarker; alpha-synuclein; Phosphorylation; DATATOP ID CEREBROSPINAL-FLUID; RAT MODEL; BLOOD-PLASMA; AMYLOID-BETA; IN-VIVO; SER-129; DEMENTIA; NEURODEGENERATION; NEUROTOXICITY; PROGRESSION AB Introduction: alpha a-Synuclein (alpha-syn) is a key protein in Parkinson's disease (PD), and one of its phosphorylated forms, pS129, is higher in PD patients than healthy controls. However, few studies have examined its levels in longitudinally collected cerebrospinal fluid (CSF) or in preclinical cases. In this study, CSF and clinical data were contributed by >300 subjects from three cohorts (the longitudinal DATATOP cohort, a large cross-sectional cohort, and a cohort of LRRK2 mutation carriers). Results: Consistent with our previous observation that CSF pS129 positively correlated with Unified Parkinson's Disease Rating Scale (UPDRS) scores, CSF pS129 in the DATATOP cohort increased over approximately two years of disease progression (mean change 5.60 pg/ml, p = 0.050). Intriguingly, in the DATATOP cohort, pS129 negatively correlated with UPDRS scores at the baseline (R = -0.244, p = 0.017), but not final point, suggesting that this association may depend on disease stage. Reanalysis of our previous cohort with stratification by PD stage, and addition of a cohort of LRRK2 mutation carriers with very early/preclinical PD, supported the idea that the relationship between CSF pS129 and disease severity over a wider range of PD stages might be represented with a U-shaped curve, in which lower pS129 levels correlated with worse clinical condition at early stages, but better condition at later stages. Conclusion: The observation of a negative-to-positive transition of correlation of pS129 to disease severity as PD progresses could have profound impact on how pS129 is used as a biomarker clinically as well as in modeling PD experimentally. C1 [Stewart, Tessandra; Ginghina, Carmen; Liu, Changqin; Shi, Min; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Sossi, Vesna] Univ British Columbia, Vancouver Hosp & Hlth Sci Ctr, Dept Phys & Astron, Vancouver, BC V5Z 1M9, Canada. [Aasly, Jan O.] St Olavs Hosp, Dept Neurol, Trondheim, Norway. [Wszolek, Zbigniew K.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Hasegawa, Kazuko; Yokoyama, Teruo] Sagamihara Natl Hosp, Natl Hosp Org, Dept Neurol, Kanagawa, Japan. [Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Educ & Clin Ctr, Geriatr Res, Seattle, WA USA. [Zabetian, Cyrus P.; Leverenz, James B.] Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA. [Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Educ & Clin Ctr, Mental Illness Res, Seattle, WA USA. [Stoessl, Alexander Jon] Univ British Columbia, Pacific Parkinsons Res Ctr, Vancouver Coastal Hlth, Vancouver, BC V5Z 1M9, Canada. [Wang, Yu] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Neurosurg, Wuhan 430030, Hubei, Peoples R China. [Liu, Changqin] Xiamen Univ, Affiliated Hosp 1, Dept Endocrinol & Metab, Xiamen, Peoples R China. [Liu, Changqin] Xiamen Univ, Affiliated Hosp 1, Xiamen Diabet Inst, Xiamen, Peoples R China. [Cain, Kevin C.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Auinger, Peggy] Univ Rochester, Sch Med & Dent, Ctr Human Expt Therapeut, Dept Neurol, Rochester, NY USA. [Kang, Un Jung] Univ Chicago Med & Biol Sci, Dept Neurol, Chicago, IL USA. [Jensen, Poul Henning] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, 325 9th Ave,HMC Box 359635, Seattle, WA 98104 USA. EM zhangj@uw.edu FU NIA NIH HHS [R01 AG033398]; NIEHS NIH HHS [P30 ES007033-6364, R01 ES016873, P42 ES004696-5897, R01 ES019277, T32 ES007032, T32 ES015459]; NINDS NIH HHS [P50 NS072187, P50 NS062684-6221, R01 NS057567, R01 NS065070, U01 NS082137] NR 35 TC 11 Z9 11 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2051-5960 J9 ACTA NEUROPATHOL COM JI Acta Neuropathol. Commun. PD JAN 31 PY 2015 VL 3 AR 7 DI 10.1186/s40478-015-0185-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CS6AI UT WOS:000362159000003 PM 25637461 ER PT J AU Greaney, ML Sprunck-Harrild, K Ruddy, KJ Ligibel, J Barry, WT Baker, E Meyer, M Emmons, KM Partridge, AH AF Greaney, Mary L. Sprunck-Harrild, Kim Ruddy, Kathryn J. Ligibel, Jennifer Barry, William T. Baker, Emily Meyer, Meghan Emmons, Karen M. Partridge, Ann H. TI Study protocol for Young & Strong: a cluster randomized design to increase attention to unique issues faced by young women with newly diagnosed breast cancer SO BMC PUBLIC HEALTH LA English DT Article DE Breast cancer; Oncology; Young women; Fertility; Exercise; Psychosocial distress; Patient communication ID QUALITY-OF-LIFE; FERTILITY CONCERNS; PRIMARY-CARE; SURVIVORS; HEALTH; AGE; PREMENOPAUSAL; INTERVENTIONS; PRESERVATION; CHEMOTHERAPY AB Background: Each year, approximately 11% of women diagnosed with breast cancer in the United States are 45 years of age or younger. These women have concerns specific to or accentuated by their age, including fertility-related concerns, and have higher rates of psychosocial distress than women diagnosed at older ages. Current guidelines recommend that fertility risks be considered early in all treatment plans; however, the extant research indicates that attention to fertility by the healthcare team is limited. Importantly, attention to fertility may be a proxy for whether or not other important issues warranting attention in younger women with breast cancer are addressed, including genetic risks, psychosocial distress, sexual functioning, and body image concerns. The Young & Strong study tests the efficacy of an intervention designed for young women recently diagnosed with breast cancer and their oncologists with the intention to: 1) increase attention to fertility as an important surrogate for other issues facing young women, 2) educate and support young women and their providers, and 3) reduce psychosocial distress among young women with breast cancer. Methods/Design: The study employs a cluster randomized design including 14 academic institutions and 40 community sites across the U.S. assigned to either the study intervention arm or contact-time comparison intervention arm. Academic institutions enroll up to 15 patients per site while community sites enroll up to 10 patients. Patient eligibility requirements include: an initial diagnosis of stage I-III invasive breast cancer within three months prior, without a known recurrence or metastatic breast cancer; 18-45 years of age at diagnosis; ability to read and write in English. The primary outcome is oncologists' attention to fertility concerns as determined by medical record review. Secondary outcomes include differences in patient satisfaction with care and psychosocial distress between the two study arms. Discussion: Study findings will provide valuable insight into how to increase attention to fertility and other issues specific to young women with breast cancer and how to improve doctor-patient communication around these issues, which may promote better quality of care for this population. C1 [Greaney, Mary L.] Univ Rhode Isl, Kingston, RI 02881 USA. [Sprunck-Harrild, Kim; Ligibel, Jennifer; Barry, William T.; Baker, Emily; Meyer, Meghan; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Ruddy, Kathryn J.] Mayo Clin, Rochester, MN USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ligibel, Jennifer; Partridge, Ann H.] Harvard Univ, Sch Med, Boston, MA USA. RP Greaney, ML (reprint author), Univ Rhode Isl, Kingston, RI 02881 USA. EM mgreaney@uri.edu FU ASCO Cancer Foundation/Susan G. Komen Improving Cancer Care Grant; NIH [5 K05 CA124415-05] FX This work was supported by an ASCO Cancer Foundation/Susan G. Komen Improving Cancer Care Grant (PI: Partridge) and by NIH 5 K05 CA124415-05 (PI: K. Emmons). Study-related materials were developed in partnership with the DF/HCC Health Communication Core, Boston, MA. We would like to thank all the women who participated in the focus groups, key informant interviews, and in the Young & Strong pilot and parent study, as well as the oncologists, providers, site coordinators, and other study staff at the sites. NR 50 TC 1 Z9 1 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD JAN 31 PY 2015 VL 15 AR 37 DI 10.1186/s12889-015-1346-9 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CB1WN UT WOS:000349418800002 PM 25636332 ER PT J AU Shen, HS Liang, D Luo, MY Duan, CJ Cai, WL Zhu, SS Qiu, JP Li, WR AF Shen, Hesong Liang, Dan Luo, Mingyue Duan, Chaijie Cai, Wenli Zhu, Shanshan Qiu, Jianping Li, Wenru TI Pilot Study on Image Quality and Radiation Dose of CT Colonography with Adaptive Iterative Dose Reduction Three-Dimensional SO PLOS ONE LA English DT Article ID TUBE-CURRENT MODULATION; COLORECTAL LESIONS; MDCT COLONOGRAPHY; RECONSTRUCTION; FEASIBILITY; CANCER; RISK; REIMBURSEMENT; COLONOSCOPY; PERFORMANCE AB Objective To investigate image quality and radiation dose of CT colonography (CTC) with adaptive iterative dose reduction three-dimensional (AIDR3D). Methods Ten segments of porcine colon phantom were collected, and 30 pedunculate polyps with diameters ranging from 1 to 15 mm were simulated on each segment. Image data were acquired with tube voltage of 120 kVp, and current doses of 10 mAs, 20 mAs, 30 mAs, 40 mAs, 50 mAs, respectively. CTC images were reconstructed using filtered back projection (FBP) and AIDR3D. Two radiologists blindly evaluated image quality. Quantitative evaluation of image quality included image noise, signal-to-noise ratio (SNR), and contrast-tonoise ratio (CNR). Qualitative image quality was evaluated with a five-score scale. Radiation dose was calculated based on dose-length product. Ten volunteers were examined supine 50 mAs with FBP and prone 20 mAs with AIDR3D, and image qualities were assessed. Paired t test was performed for statistical analysis. Results For 20 mAs with AIDR3D and 50 mAs with FBP, image noise, SNRs and CNRs were (16.4 +/- 1.6) HU vs. (16.8 +/- 2.6) HU, 1.9 +/- 0.2 vs. 1.9 +/- 0.4, and 62.3 +/- 6.8 vs. 62.0 +/- 6.2, respectively; qualitative image quality scores were 4.1 and 4.3, respectively; their differences were all not statistically significant. Compared with 50 mAs with FBP, radiation dose (1.62 mSv) of 20 mAs with AIDR3D was decreased by 60.0%. There was no statistically significant difference in image noise, SNRs, CNRs and qualitative image quality scores between prone 20 mAs with AIDR3D and supine 50 mAs with FBP in 10 volunteers, the former reduced radiation dose by 61.1%. Conclusion Image quality of CTC using 20 mAs with AIDR3D could be comparable to standard 50 mAs with FBP, radiation dose of the former reduced by about 60.0% and was only 1.62 mSv. C1 [Shen, Hesong; Liang, Dan; Luo, Mingyue; Zhu, Shanshan; Qiu, Jianping; Li, Wenru] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiol, Guangzhou 510275, Guangdong, Peoples R China. [Duan, Chaijie] Tsinghua Univ, Grad Sch Shenzhen, Biomed Engn Res Ctr, Shenzhen 518057, Guangdong, Peoples R China. [Cai, Wenli] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli] Harvard Univ, Sch Med, Boston, MA USA. RP Luo, MY (reprint author), Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiol, Guangzhou 510275, Guangdong, Peoples R China. EM myluo720@163.com RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 FU National Natural Science Foundation of China [81230035]; Guangdong Provincial Science and Technology Program [2011B031800182, 2013B051000016] FX This study was supported by The National Natural Science Foundation of China (81230035), http://www.nsfc.gov.cn/; and Guangdong Provincial Science and Technology Program (2011B031800182, 2013B051000016), http://pro.gdstc.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 1 Z9 1 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 30 PY 2015 VL 10 IS 1 AR e0117116 DI 10.1371/journal.pone.0117116 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC9HX UT WOS:000350680700070 PM 25635839 ER PT J AU Courties, G Herisson, F Sager, HB Heidt, T Ye, YX Wei, Y Sun, Y Severe, N Dutta, P Scharff, J Scadden, DT Weissleder, R Swirski, FK Moskowitz, MA Nahrendorf, M AF Courties, Gabriel Herisson, Fanny Sager, Hendrik B. Heidt, Timo Ye, Yuxiang Wei, Ying Sun, Yuan Severe, Nicolas Dutta, Partha Scharff, Jennifer Scadden, David T. Weissleder, Ralph Swirski, Filip K. Moskowitz, Michael A. Nahrendorf, Matthias TI Ischemic Stroke Activates Hematopoietic Bone Marrow Stem Cells SO CIRCULATION RESEARCH LA English DT Article DE bone marrow; hematopoietic stem cells; monocyte; stroke ID FOCAL CEREBRAL-ISCHEMIA; INNATE IMMUNE-SYSTEM; MYOCARDIAL-INFARCTION; POSTSTROKE INFECTION; INFLAMMATORY CELLS; BETA-BLOCKERS; BRAIN; ATHEROSCLEROSIS; MACROPHAGES; NICHE AB Rationale: The mechanisms leading to an expanded neutrophil and monocyte supply after stroke are incompletely understood. Objective: To test the hypothesis that transient middle cerebral artery occlusion (tMCAO) in mice leads to activation of hematopoietic bone marrow stem cells. Methods and Results: Serial in vivo bioluminescence reporter gene imaging in mice with tMCAO revealed that bone marrow cell cycling peaked 4 days after stroke (P<0.05 versus pre tMCAO). Flow cytometry and cell cycle analysis showed activation of the entire hematopoietic tree, including myeloid progenitors. The cycling fraction of the most upstream hematopoietic stem cells increased from 3.34%+/- 0.19% to 7.32%+/- 0.52% after tMCAO (P<0.05). In vivo microscopy corroborated proliferation of adoptively transferred hematopoietic progenitors in the bone marrow of mice with stroke. The hematopoietic system's myeloid bias was reflected by increased expression of myeloid transcription factors, including PU.1 (P<0.05), and by a decline in lymphocyte precursors. In mice after tMCAO, tyrosine hydroxylase levels in sympathetic fibers and bone marrow noradrenaline levels rose (P<0.05, respectively), associated with a decrease of hematopoietic niche factors that promote stem cell quiescence. In mice with genetic deficiency of the beta(3) adrenergic receptor, hematopoietic stem cells did not enter the cell cycle in increased numbers after tMCAO (naive control, 3.23 +/- 0.22; tMCAO, 3.74 +/- 0.33, P=0.51). Conclusions: Ischemic stroke activates hematopoietic stem cells via increased sympathetic tone, leading to a myeloid bias of hematopoiesis and higher bone marrow output of inflammatory Ly6C(high) monocytes and neutrophils. C1 [Courties, Gabriel; Sager, Hendrik B.; Heidt, Timo; Ye, Yuxiang; Sun, Yuan; Dutta, Partha; Scharff, Jennifer; Weissleder, Ralph; Swirski, Filip K.; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Courties, Gabriel; Sager, Hendrik B.; Heidt, Timo; Ye, Yuxiang; Sun, Yuan; Dutta, Partha; Scharff, Jennifer; Weissleder, Ralph; Swirski, Filip K.; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Herisson, Fanny; Wei, Ying; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA USA. [Herisson, Fanny; Wei, Ying; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Neurol, Charlestown, MA USA. [Severe, Nicolas; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Nahrendorf, M (reprint author), Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU National Institutes of Health [R01-NS084863, R01-HL117829, R01-HL096576, HHSN268201000044C]; MGH Research Scholar Award; American Heart Association [13POST16580004]; German Research Foundation [HE6382/1-1, SA1668/2-1]; Deutsche Herzstiftung [S/05/12] FX This work was funded in part by grants from the National Institutes of Health (R01-NS084863, R01-HL117829, R01-HL096576, HHSN268201000044C), the MGH Research Scholar Award, the American Heart Association (13POST16580004), the German Research Foundation (HE6382/1-1 and SA1668/2-1), and the Deutsche Herzstiftung (S/05/12). NR 52 TC 27 Z9 28 U1 2 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD JAN 30 PY 2015 VL 116 IS 3 BP 407 EP + DI 10.1161/CIRCRESAHA.116.305207 PG 19 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA CA3IJ UT WOS:000348799500007 PM 25362208 ER PT J AU Newton, RH Lu, Y Papa, A Whitcher, GH Kang, YJ Yan, C Pandolfi, PP Turka, LA AF Newton, Ryan H. Lu, Yu Papa, Antonella Whitcher, Greg H. Kang, Youn-Jung Yan, Catherine Pandolfi, Pier Paolo Turka, Laurence A. TI Suppression of T-cell lymphomagenesis in mice requires PTEN phosphatase activity SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-SUPPRESSOR; GENOMIC INSTABILITY; NEGATIVE REGULATION; NUCLEAR PTEN; PTEN/MMAC1; INACTIVATION; MANNER; GENE AB Mice with T-cell-specific loss of the tumor suppressor gene PTEN early in T-cell ontogeny develop thymic lymphomas that invariably harbor a reciprocal translocation involving the T-cell receptor alpha/delta locus and c-myc, t(14; 15). In addition to its known function as a lipid phosphatase opposing PI3K signaling, PTEN has also been described as playing a prominent role in promoting genomic stability. As a result, it has been uncertain which one(s) of these 2 separable features were required to block the development of lymphoma. Here, using a conditional model in which T cells selectively express 1 phosphatase-dead PTEN mutant (C124S) and maintain 1 null allele, we show that PTEN phosphatase activity is required for preventing the emergence of a malignant T-cell population harboring t(14; 15), thus constituting a critical function of PTEN in preventing lymphomagenesis. C1 [Newton, Ryan H.; Whitcher, Greg H.; Turka, Laurence A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02129 USA. [Newton, Ryan H.; Whitcher, Greg H.; Turka, Laurence A.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02129 USA. [Lu, Yu] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Papa, Antonella; Pandolfi, Pier Paolo] Beth Israel Deaconess Canc Ctr, Canc Res Inst, Boston, MA USA. [Papa, Antonella; Pandolfi, Pier Paolo] Beth Israel Deaconess Med Ctr, Dept Pathol & Med, Boston, MA 02215 USA. [Kang, Youn-Jung; Yan, Catherine] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Kang, Youn-Jung] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. RP Turka, LA (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, 149 13th St,Room 5101, Boston, MA 02129 USA. EM lturka@partners.org OI Papa, Antonella/0000-0001-8653-7121 NR 25 TC 4 Z9 4 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 29 PY 2015 VL 125 IS 5 BP 852 EP 855 DI 10.1182/blood-2014-04-571372 PG 4 WC Hematology SC Hematology GA CD1DR UT WOS:000350814900019 PM 25477498 ER PT J AU Lawrence, MS Sougnez, C Lichtenstein, L Cibulskisl, K Lander, E Gabriel, SB Getz, G Ally, A Balasundaram, M Birol, I Bowlby, R Brooks, D Butterfield, YSN Carlsen, R Cheng, D Chu, A Dhalla, N Guin, R Holt, RA Jones, SJM Lee, D Li, HYI Marra, MA Mayo, M Moore, RA Mungall, AJ Robertson, AG Schein, JE Sipahimalan, P Tam, A Thiessen, N Wong, T Protopopov, A Santoso, N Lee, S Parfenov, M Zhang, JH Mahadeshwar, HS Tang, JB Ren, XJ Seth, S Haseley, P Zeng, D Yang, LX Xu, AW Song, XZ Pantazi, A Bristow, CA Hadjipanayis, A Seidman, J Chin, L Park, PJ Kucherlapati, R Akbani, R Casasent, T Liu, WB Le, Y Mille, G Motter, T Weinstein, J Diao, LX Wang, J Fan, YH Lie, JZ Wang, K Auman, JT Balu, S Bodenheimer, T Buda, E Hayes, DN Hoadley, KA Hoyle, AP Jefferys, SR Jones, CD Kimes, PK Liu, YF Marron, JS Meng, SW Mieczkowski, PA Mose, LE Parker, JS Perou, CM Prins, JF Roach, J Shi, Y Simons, JV Singh, D Soloway, MG Tan, DH Veluvolu, U Walter, V Waring, S Wilkerson, MD Wu, JY Zhao, N Cherniack, AD Hammerman, PS Tward, AD Pedamallu, CS Saksena, G Jung, J Ojesina, AI Carter, SL Zack, TI Schumacher, SE Beroukhim, R Freeman, SS Meyerson, M Cho, J Chin, L Getz, G Noble, MS DiCara, D Zhang, H Heiman, DI Gehlenborg, N Voet, D Lin, P Frazer, S Stojanov, P Liu, YC Zou, LH Kim, J Sougnez, C Gabriel, SB Lawrence, MS Muzny, D Doddapaneni, H Kovar, C Reid, J Morton, D Han, Y Hale, W Chao, H Chang, K Drummond, JA Gibbs, RA Kakkar, N Wheeler, D Xi, L Ciriello, G Ladanyi, M Lee, W Ramirez, R Sander, C Shen, R Sinhal, R Weinhold, N Taylor, BS Aksoy, BA Dresdner, G Gao, JJ Gross, B Jacobsen, A Reva, B Schultz, N Sumer, SO Sun, YC Chan, TA Morris, LG Stuart, J Benz, S Ng, S Benz, C Yau, C Baylin, SB Cope, L Danilova, L Herman, JG Bootwalla, M Maglinte, DT Larid, PW Triche, T Weisenberger, DJ Van den Berg, DJ Agrawal, N Bishop, J Boutros, PC Bruce, JP Byers, LA Califano, J Carey, TE Chen, Z Cheng, H Chiosea, SI Cohen, E Diergaarde, B Egloff, AM El-Naggar, AK Ferris, RL Frederick, MJ Grandis, JR Guo, Y Haddad, RI Hammerman, PS Harris, T Hayes, DN Hui, ABY Lee, JJ Lippman, SM Liu, FF McHugh, JB Myers, J Ng, PKS Perez-Ordonez, B Pickering, CR Prystowsky, M Romkes, M Saleh, AD Sartor, MA Seethala, R Seiwert, TY Si, H Tward, AD Van Waes, C Waggott, DM Wiznerowicz, M Yarbrough, WG Zhang, JX Zuo, ZX Burnett, K Crain, D Gardner, J Lau, K Mallery, D Morris, S Lauskis, JP Penny, R Shelton, C Shelton, T Sherman, M Yena, P Black, AD Bowen, J Frick, J Gastier-Foster, JM Harper, HA Leraas, K Lichtenberg, TM Ramirez, NC Wise, L Zmuda, E Baboud, J Jensen, MA Kahn, AB Pihl, TD Pot, DA Srinivasan, D Walton, JS Wan, YH Burton, RA Davidsen, T Demchok, JA Eley, G Ferguson, ML Shaw, KRM Ozenberger, BA Sheth, M Sofia, HJ Tarnuzzer, R Wang, ZN Yang, LM Zenklusen, JC Saller, C Tarvi, K Chen, C Bollag, R Weinberger, P Golusinski, W Golusinski, P Ibbs, M Korski, K Mackiewicz, A Suchorska, W Szybiak, B Wiznerowicz, M Burnett, K Curley, E Gardner, J Mallery, D Penny, R Shelton, T Yena, P Beard, C Mitchell, C Sandusky, G Agrawal, N Ahn, J Bishop, J Califano, J Khan, Z Bruce, JP Hui, ABY Irish, J Liu, FF Perez-Ordonez, B Waldron, J Boutros, PC Waggott, DM Myers, J William, WN Lippman, SM Egea, S Gomez-Fernandez, C Herbert, L Bradford, CR Carey, TE Chepeha, DB Haddad, AS Jones, TR Komarck, CM Malakh, M McHugh, JB Moyer, JS Nguyen, A Peterson, LA Prince, ME Rozek, LS Sartor, MA Taylor, EG Walline, HM Wolf, GT Boice, L Chera, BS Funkhouser, WK Gulley, ML Hackman, TG Hayes, DN Hayward, MC Huang, M Rathmell, WK Salazar, AH Shockley, WW Shores, CG Thorne, L Weissler, MC Wrenn, S Zanation, AM Chiosea, SI Diergaarde, B Egloff, AM Ferris, RL Romkes, M Seethala, R Brown, BT Guo, Y Pham, M Yarbrough, WG AF Lawrence, Michael S. Sougnez, Carrie Lichtenstein, Lee Cibulskisl, Kristian Lander, Eric Gabriel, Stacey B. Getz, Gad Ally, Adrian Balasundaram, Miruna Birol, Inanc Bowlby, Reanne Brooks, Denise Butterfield, Yaron S. N. Carlsen, Rebecca Cheng, Dean Chu, Andy Dhalla, Noreen Guin, Ranabir Holt, Robert A. Jones, Steven J. M. Lee, Darlene Li, Haiyan I. Marra, Marco A. Mayo, Michael Moore, Richard A. Mungall, Andrew J. Robertson, A. Gordon Schein, Jacqueline E. Sipahimalan, Payal Tam, Angela Thiessen, Nina Wong, Tina Protopopov, Alexei Santoso, Netty Lee, Semin Parfenov, Michael Zhang, Jianhua Mahadeshwar, Harshad S. Tang, Jiabin Ren, Xiaojia Seth, Sahil Haseley, Psalm Zeng, Dong Yang, Lixing Xu, Andrew W. Song, Xingzhi Pantazi, Angeliki Bristow, Christopher A. Hadjipanayis, Angela Seidman, Jonathan Chin, Lynda Park, Peter J. Kucherlapati, Raju Akbani, Rehan Casasent, Tod Liu, Wenbin Le, Yiling Mille, Gordon Motter, Thomas Weinstein, John Diao, Lixia Wang, Jing Fan, You Hong Lie, Jinze Wang, Kai Auman, J. Todd Balu, Saianand Bodenheimer, Thomas Buda, Elizabeth Hayes, D. Neil Hoadley, Katherine A. Hoyle, Alan P. Jefferys, Stuart R. Jones, Corbin D. Kimes, Patrick K. Liu, Yufeng Marron, J. S. Meng, Shaowu Mieczkowski, Piotr A. Mose, Lisle E. Parker, Joel S. Perou, Charles M. Prins, Jan F. Roach, Jeffrey Shi, Yan Simons, Janae V. Singh, Darshan Soloway, Matthew G. Tan, Donghui Veluvolu, Umadevi Walter, Vonn Waring, Scot Wilkerson, Matthew D. Wu, Junyuan Zhao, Ni Cherniack, Andrew D. Hammerman, Peter S. Tward, Aaron D. Pedamallu, Chandra Sekhar Saksena, Gordon Jung, Joonil Ojesina, Akinyemi I. Carter, Scott L. Zack, Travis I. Schumacher, Steven E. Beroukhim, Rameen Freeman, Samuel S. Meyerson, Matthew Cho, Juok Chin, Lynda Getz, Gad Noble, Michael S. DiCara, Daniel Zhang, Hailei Heiman, David I. Gehlenborg, Nils Voet, Doug Lin, Pei Frazer, Scott Stojanov, Petar Liu, Yingchun Zou, Lihua Kim, Jaegil Sougnez, Carrie Gabriel, Stacey B. Lawrence, Michael S. Muzny, Donna Doddapaneni, HarshaVardhan Kovar, Christie Reid, Jeff Morton, Donna Han, Yi Hale, Walker Chao, Hsu Chang, Kyle Drummond, Jennifer A. Gibbs, Richard A. Kakkar, Nipun Wheeler, David Xi, Liu Ciriello, Giovanni Ladanyi, Marc Lee, William Ramirez, Ricardo Sander, Chris Shen, Ronglai Sinhal, Rileen Weinhold, Nils Taylor, Barry S. Aksoy, B. Arman Dresdner, Gideon Gao, Jianjiong Gross, Benjamin Jacobsen, Anders Reva, Boris Schultz, Nikolaus Sumer, S. Onur Sun, Yichao Chan, Timothy A. Morris, Luc G. Stuart, Joshua Benz, Stephen Ng, Sam Benz, Christopher Yau, Christina Baylin, Stephen B. Cope, Leslie Danilova, Ludmila Herman, James G. Bootwalla, Moiz Maglinte, Dennis T. Larid, Peter W. Triche, Timothy, Jr. Weisenberger, Daniel J. Van den Berg, David J. Agrawal, Nishant Bishop, Justin Boutros, Paul C. Bruce, Jeff P. Byers, Lauren Averett Califano, Joseph Carey, Thomas E. Chen, Zhong Cheng, Hui Chiosea, Simion I. Cohen, Ezra Diergaarde, Brenda Egloff, Ann Marie El-Naggar, Adel K. Ferris, Robert L. Frederick, Mitchell J. Grandis, Jennifer R. Guo, Yan Haddad, Robert I. Hammerman, Peter S. Harris, Thomas Hayes, D. Neil Hui, Angela B. Y. Lee, J. Jack Lippman, Scott M. Liu, Fei-Fei McHugh, Jonathan B. Myers, Jeff Ng, Patrick Kwok Shing Perez-Ordonez, Bayardo Pickering, Curtis R. Prystowsky, Michael Romkes, Marjorie Saleh, Anthony D. Sartor, Maureen A. Seethala, Raja Seiwert, Tanguy Y. Si, Han Tward, Aaron D. Van Waes, Carter Waggott, Daryl M. Wiznerowicz, Maciej Yarbrough, Wendell G. Zhang, Jiexin Zuo, Zhixiang Burnett, Ken Crain, Daniel Gardner, Johanna Lau, Kevin Mallery, David Morris, Scott Lauskis, Joseph Pau Penny, Robert Shelton, Candace Shelton, Troy Sherman, Mark Yena, Peggy Black, Aaron D. Bowen, Jay Frick, Jessica Gastier-Foster, Julie M. Harper, Hollie A. Leraas, Kristen Lichtenberg, Tara M. Ramirez, Nilsa C. Wise, Lisa Zmuda, Erik Baboud, Julien Jensen, Mark A. Kahn, An B. Pihl, Todd D. Pot, David A. Srinivasan, Deepak Walton, Jessica S. Wan, Yunhu Burton, Robert A. Davidsen, Tanja Demchok, John A. Eley, Greg Ferguson, Martin L. Shaw, Kenna R. Mills Ozenberger, Bradley A. Sheth, Margi Sofia, Heidi J. Tarnuzzer, Roy Wang, Zhining Yang, Liming Zenklusen, Jean Claude Saller, Charles Tarvi, Katherine Chen, Chu Bollag, Roni Weinberger, Paul Golusinski, Wojciech Golusinski, Pawel Ibbs, Matthew Korski, Konstanty Mackiewicz, Andrzej Suchorska, Wiktoria Szybiak, Bartosz Wiznerowicz, Maciej Burnett, Ken Curley, Erin Gardner, Johanna Mallery, David Penny, Robert Shelton, Troy Yena, Peggy Beard, Christina Mitchell, Colleen Sandusky, George Agrawal, Nishant Ahn, Julie Bishop, Justin Califano, Joseph Khan, Zubair Bruce, Jeff P. Hui, Angela B. Y. Irish, Jonathan Liu, Fei-Fei Perez-Ordonez, Bayardo Waldron, John Boutros, Paul C. Waggott, Daryl M. Myers, Jeff William, William N., Jr. Lippman, Scott M. Egea, Sophie Gomez-Fernandez, Carmen Herbert, Lynn Bradford, Carol R. Carey, Thomas E. Chepeha, Douglas B. Haddad, Andrea S. Jones, Tamara R. Komarck, Christine M. Malakh, Mayya McHugh, Jonathan B. Moyer, Jeffrey S. Nguyen, Ariane Peterson, Lisa A. Prince, Mark E. Rozek, Laura S. Sartor, Maureen A. Taylor, Evan G. Walline, Heather M. Wolf, Gregory T. Boice, Lori Chera, Bhishamjit S. Funkhouser, William K. Gulley, Margaret L. Hackman, Trevor G. Hayes, D. Neil Hayward, Michele C. Huang, Mei Rathmell, W. Kimryn Salazar, Ashley H. Shockley, William W. Shores, Carol G. Thorne, Leigh Weissler, Mark C. Wrenn, Sylvia Zanation, Adam M. Chiosea, Simion I. Diergaarde, Brenda Egloff, Ann Marie Ferris, Robert L. Romkes, Marjorie Seethala, Raja Brown, Brandee T. Guo, Yan Pham, Michelle Yarbrough, Wendell G. CA Canc Genome Atlas Network TI Comprehensive genomic characterization of head and neck squamous cell carcinomas SO NATURE LA English DT Article ID NF-KAPPA-B; GROWTH-FACTOR-RECEPTOR; AJUBA FAMILY PROTEINS; CANCER GROWTH; ACTIVATION; EXPRESSION; TRAF3; EGFR; CLASSIFICATION; RESISTANCE AB The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs. C1 [Lichtenstein, Lee; Cibulskisl, Kristian; Lander, Eric; Gabriel, Stacey B.; Cherniack, Andrew D.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Jung, Joonil; Ojesina, Akinyemi I.; Carter, Scott L.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Freeman, Samuel S.; Meyerson, Matthew; Cho, Juok; Noble, Michael S.; DiCara, Daniel; Zhang, Hailei; Heiman, David I.; Gehlenborg, Nils; Voet, Doug; Lin, Pei; Frazer, Scott; Stojanov, Petar; Liu, Yingchun; Zou, Lihua; Kim, Jaegil] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Cheng, Dean; Chu, Andy; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J. M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalan, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada. [Protopopov, Alexei; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Seth, Sahil; Zeng, Dong; Song, Xingzhi; Bristow, Christopher A.; Akbani, Rehan; Casasent, Tod; Liu, Wenbin; Le, Yiling; Mille, Gordon; Motter, Thomas; Weinstein, John; Diao, Lixia; Wang, Jing; Fan, You Hong; Byers, Lauren Averett; El-Naggar, Adel K.; Frederick, Mitchell J.; Lee, J. Jack; Myers, Jeff; Ng, Patrick Kwok Shing; Pickering, Curtis R.; Zhang, Jiexin; William, William N., Jr.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Santoso, Netty; Lee, Semin; Parfenov, Michael; Ren, Xiaojia; Haseley, Psalm; Yang, Lixing; Xu, Andrew W.; Pantazi, Angeliki; Hadjipanayis, Angela; Seidman, Jonathan; Park, Peter J.; Kucherlapati, Raju; Beroukhim, Rameen; Meyerson, Matthew; Tward, Aaron D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hadjipanayis, Angela; Park, Peter J.; Kucherlapati, Raju] Brigham & Womens Hosp, Boston, MA 02115 USA. [Park, Peter J.] Boston Childrens Hosp, Boston, MA 02115 USA. [Lie, Jinze; Wang, Kai] Univ Kentucky, Lexington, KY 40506 USA. [Auman, J. Todd; Balu, Saianand; Bodenheimer, Thomas; Buda, Elizabeth; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Kimes, Patrick K.; Liu, Yufeng; Marron, J. S.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Parker, Joel S.; Perou, Charles M.; Prins, Jan F.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Singh, Darshan; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Walter, Vonn; Waring, Scot; Wilkerson, Matthew D.; Wu, Junyuan; Zhao, Ni; Boice, Lori; Chera, Bhishamjit S.; Funkhouser, William K.; Gulley, Margaret L.; Hackman, Trevor G.; Hayward, Michele C.; Huang, Mei; Rathmell, W. Kimryn; Salazar, Ashley H.; Shockley, William W.; Shores, Carol G.; Thorne, Leigh; Weissler, Mark C.; Wrenn, Sylvia; Zanation, Adam M.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Pedamallu, Chandra Sekhar; Ojesina, Akinyemi I.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Meyerson, Matthew; Stojanov, Petar; Haddad, Robert I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zack, Travis I.] Harvard Univ, Boston, MA 02115 USA. [Muzny, Donna; Doddapaneni, HarshaVardhan; Kovar, Christie; Reid, Jeff; Morton, Donna; Han, Yi; Hale, Walker; Chao, Hsu; Chang, Kyle; Drummond, Jennifer A.; Gibbs, Richard A.; Kakkar, Nipun; Wheeler, David; Xi, Liu] Baylor Coll Med, Houston, TX 77030 USA. [Ciriello, Giovanni; Ladanyi, Marc; Lee, William; Ramirez, Ricardo; Sander, Chris; Shen, Ronglai; Sinhal, Rileen; Weinhold, Nils; Taylor, Barry S.; Aksoy, B. Arman; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Reva, Boris; Schultz, Nikolaus; Sumer, S. Onur; Sun, Yichao; Chan, Timothy A.; Morris, Luc G.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Stuart, Joshua; Benz, Stephen; Ng, Sam; Benz, Christopher; Yau, Christina] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. [Baylin, Stephen B.; Cope, Leslie; Danilova, Ludmila; Herman, James G.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Bootwalla, Moiz; Maglinte, Dennis T.; Larid, Peter W.; Triche, Timothy, Jr.; Weisenberger, Daniel J.; Van den Berg, David J.] Univ So Calif, Los Angeles, CA 90033 USA. [Agrawal, Nishant; Bishop, Justin; Califano, Joseph; Ahn, Julie; Khan, Zubair] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Boutros, Paul C.; Waggott, Daryl M.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. [Bruce, Jeff P.; Hui, Angela B. Y.] Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. [Carey, Thomas E.; McHugh, Jonathan B.; Sartor, Maureen A.; Bradford, Carol R.; Chepeha, Douglas B.; Haddad, Andrea S.; Jones, Tamara R.; Komarck, Christine M.; Malakh, Mayya; Moyer, Jeffrey S.; Nguyen, Ariane; Peterson, Lisa A.; Prince, Mark E.; Rozek, Laura S.; Taylor, Evan G.; Walline, Heather M.; Wolf, Gregory T.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Chen, Zhong; Cheng, Hui; Saleh, Anthony D.; Si, Han; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. [Chiosea, Simion I.; Diergaarde, Brenda; Egloff, Ann Marie; Ferris, Robert L.; Grandis, Jennifer R.; Romkes, Marjorie; Seethala, Raja] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Cohen, Ezra; Seiwert, Tanguy Y.; Zuo, Zhixiang] Univ Chicago, Chicago, IL 60637 USA. [Guo, Yan; Brown, Brandee T.; Pham, Michelle] Vanderbilt Univ, Med Ctr, Med Ctr East 7209, Nashville, TN 37232 USA. [Harris, Thomas; Prystowsky, Michael] Albert Einstein Coll Med, Bronx, NY 10461 USA. [Lippman, Scott M.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Liu, Fei-Fei; Irish, Jonathan; Waldron, John] Univ Toronto, Toronto, ON M5G 2M9, Canada. [Perez-Ordonez, Bayardo] Univ Hlth Network, Toronto, ON M5G 2C4, Canada. [Wiznerowicz, Maciej; Golusinski, Wojciech; Golusinski, Pawel; Ibbs, Matthew; Korski, Konstanty; Mackiewicz, Andrzej; Suchorska, Wiktoria; Szybiak, Bartosz] Greater Poland Canc Ctr, PL-61866 Poznan, Poland. [Yarbrough, Wendell G.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Burnett, Ken; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Lauskis, Joseph Pau; Shelton, Candace; Shelton, Troy; Sherman, Mark; Yena, Peggy; Curley, Erin] Int Genom Consortium, Phoenix, AZ 85004 USA. [Black, Aaron D.; Bowen, Jay; Frick, Jessica; Gastier-Foster, Julie M.; Harper, Hollie A.; Leraas, Kristen; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA. [Baboud, Julien; Jensen, Mark A.; Kahn, An B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Walton, Jessica S.; Wan, Yunhu] SRA Int, Fairfax, VA 22033 USA. [Burton, Robert A.] Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Davidsen, Tanja; Demchok, John A.; Ferguson, Martin L.; Shaw, Kenna R. Mills; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude] NCI, Bethesda, MD 20892 USA. [Eley, Greg] Scimentis LLC, Atlanta, GA 30666 USA. [Ozenberger, Bradley A.; Sofia, Heidi J.] NHGRI, NIH, Bethesda, MD 20892 USA. [Saller, Charles; Tarvi, Katherine] Analyt Biol Serv Inc, St Petersburg 198013, Russia. [Chen, Chu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Bollag, Roni; Weinberger, Paul] Georgia Regents Univ, Augusta, GA 30912 USA. [Beard, Christina; Mitchell, Colleen; Sandusky, George] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46202 USA. [Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. RP Hayes, DN (reprint author), Univ N Carolina, Chapel Hill, NC 27599 USA. EM hayes@med.unc.edu; anaggar@mdanderson.org; grandisjr@upmc.edu RI Schein, Jacquie/G-3674-2015; Weinberger, Paul/B-7007-2008; Holt, Robert/C-3303-2009; Zhao, Ni/P-9086-2014; Marra, Marco/B-5987-2008; Jones, Steven/C-3621-2009; Zuo, Zhixiang/M-4441-2016; Lee, Semin/S-2629-2016; Birol, Inanc/G-5440-2011; OI Schultz, Nikolaus/0000-0002-0131-4904; Diergaarde, Brenda/0000-0002-3578-6547; Carey, Thomas/0000-0002-5202-7518; Seth, Sahil/0000-0003-4579-3959; Pot, David/0000-0002-1480-9826; Jacobsen, Anders/0000-0001-6847-4980; Sinha, Rileen/0000-0001-5497-5055; Perou, Charles/0000-0001-9827-2247; Gehlenborg, Nils/0000-0003-0327-8297; Weinberger, Paul/0000-0002-5885-2631; Zhao, Ni/0000-0002-7762-3949; Zuo, Zhixiang/0000-0002-2492-2689; Lee, Semin/0000-0002-9015-6046; Birol, Inanc/0000-0003-0950-7839; Ojesina, Akinyemi/0000-0003-0755-3639; Benz, Stephen/0000-0002-4067-0602; Spence, Tara/0000-0001-7098-4103 FU National Institutes of Health (NIH) [P50CA097190, P50CA16672, U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, RO1 CA 095419]; Bobby F. Garrett Fund for Head and Neck Cancer Research; NIDCD Intramural Projects [ZIA-DC-000016, 73, 74] FX This study was supported by National Institutes of Health (NIH) grants: P50CA097190, P50CA16672, U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025 and RO1 CA 095419. Supported by The Bobby F. Garrett Fund for Head and Neck Cancer Research and NIDCD Intramural Projects ZIA-DC-000016, 73 and 74. NR 45 TC 226 Z9 227 U1 27 U2 103 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 29 PY 2015 VL 517 IS 7536 BP 576 EP 582 DI 10.1038/nature14129 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA2ZL UT WOS:000348775000035 ER PT J AU Norman, JM Handley, SA Baldridge, MT Droit, L Liu, CY Keller, BC Kambal, A Monaco, CL Zhao, G Fleshner, P Stappenbeck, TS McGovern, DPB Keshavarzian, A Mutlu, EA Sauk, J Gevers, D Xavier, RJ Wang, D Parkes, M Virgin, HW AF Norman, Jason M. Handley, Scott A. Baldridge, Megan T. Droit, Lindsay Liu, Catherine Y. Keller, Brian C. Kambal, Amal Monaco, Cynthia L. Zhao, Guoyan Fleshner, Phillip Stappenbeck, Thaddeus S. McGovern, Dermot P. B. Keshavarzian, Ali Mutlu, Ece A. Sauk, Jenny Gevers, Dirk Xavier, Ramnik J. Wang, David Parkes, Miles Virgin, Herbert W. TI Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease SO CELL LA English DT Article ID HUMAN GUT VIROME; FECAL MICROBIOTA TRANSPLANTATION; CROHNS-DISEASE; STAPHYLOCOCCUS-AUREUS; METAGENOMIC ANALYSIS; BACTERIAL PATHOGENS; ULCERATIVE-COLITIS; ANTIBIOTICS INDUCE; CYSTIC-FIBROSIS; SEQUENCING DATA AB Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn's disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases. We show that the enteric virome is abnormal in CD and UC patients. In-depth analysis of preparations enriched for free virions in the intestine revealed that CD and UC were associated with a significant expansion of Caudovirales bacteriophages. The viromes of CD and UC patients were disease and cohort specific. Importantly, it did not appear that expansion and diversification of the enteric virome was secondary to changes in bacterial populations. These data support a model in which changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis. We conclude that the virome is a candidate for contributing to, or being a biomarker for, human inflammatory bowel disease and speculate that the enteric virome may play a role in other diseases. C1 [Norman, Jason M.; Handley, Scott A.; Baldridge, Megan T.; Droit, Lindsay; Liu, Catherine Y.; Keller, Brian C.; Kambal, Amal; Monaco, Cynthia L.; Zhao, Guoyan; Stappenbeck, Thaddeus S.; Wang, David; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Keller, Brian C.; Monaco, Cynthia L.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Zhao, Guoyan; Wang, David] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Fleshner, Phillip] Cedars Sinai Med Ctr, Div Colorectal Surg, Los Angeles, CA 90048 USA. [McGovern, Dermot P. B.] F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 USA. [McGovern, Dermot P. B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Keshavarzian, Ali; Mutlu, Ece A.] Rush Univ, Med Ctr, Div Digest Dis & Nutr, Dept Med, Chicago, IL 60612 USA. [Sauk, Jenny; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Sauk, Jenny; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Sauk, Jenny; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gevers, Dirk; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Parkes, Miles] Univ Cambridge, Addenbrookes Hosp, Div Gastroenterol, Cambridge CB2 0QQ, England. [Parkes, Miles] Univ Cambridge, Dept Med, Cambridge CB2 0QQ, England. RP Virgin, HW (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. EM virgin@wustl.edu RI Keller, Brian/E-2996-2016; OI Keller, Brian/0000-0003-2997-6712; Baldridge, Megan/0000-0002-7030-6131 FU Crohn's and Colitis Foundation [R01 AI084887, R01 OD011170, 3132, 274415]; Broad Medical Foundation [IBD-0357]; NIH grant [5T32AI007163-35, 5T32CA009547, T32 HL007317-36, 5T32AI007172-34]; European Union [305479]; Leona M. and Harry B. Helmsley Charitable Trust; NIHR Biomedical Research Centre awards; University of Cambridge School of Clinical Medicine; NIH Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research grant [U54 AI057160]; NCI Cancer Center Support grant [P30 CA91842]; National Center for Research Resources (NCRR) [UL1TR000448]; NIHR Biomedical Research Centre award; Agency for Healthcare Research and Quality [HS021747]; [R01 AT007143]; [DK071838]; [AT001628]; [DK062413]; [DK046763-19]; [AI067068]; [U54DE023789-01]; [U54 DE023798]; [R01 DK092405] FX H.W.V., S.A.H., and J.M.N. were supported by R01 AI084887, R01 OD011170, grants 3132 and 274415 from the Crohn's and Colitis Foundation, and grant IBD-0357 from the Broad Medical Foundation. T.S.S. was supported by grant 3132 from the Crohn's and Colitis Foundation. J.M.N. was supported by NIH grant 5T32AI007163-35. M.T.B. was supported by NIH grant 5T32CA009547. B.C.K. was supported by NIH grant T32 HL007317-36. C.L.M. was supported by NIH grant 5T32AI007172-34. A. Keshavarzian and E.A.M. were supported by R01 AT007143, DK071838, and AT001628. D.P.B.M. was supported by DK062413, DK046763-19, AI067068, and U54DE023789-01, grant HS021747 from the Agency for Healthcare Research and Quality, grant 305479 from the European Union, and The Leona M. and Harry B. Helmsley Charitable Trust. M.P. was supported by the NIHR Biomedical Research Centre awards to Addenbrooke's Hospital and University of Cambridge School of Clinical Medicine. D.W. was supported by the NIH Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research grant U54 AI057160. D.G. and R.J.X. were supported by U54 DE023798 and R01 DK092405. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support grant P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA grant UL1TR000448 from the National Center for Research Resources (NCRR), a component of the NIH, and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. We would like to thank the patients and relatives who contributed samples to this collection and the team of research nurses and coordinators who supported this activity, including Claire Dawson, Elizabeth Andersen, and Martina Lofthouse (Cambridge, UK) and Gildardo Barron (Los Angeles, USA). We also acknowledge the NIHR Biomedical Research Centre award to support research infrastructure at Addenbrooke's Hospital/University of Cambridge School of Clinical Medicine. We would also like to thank Jessica Hoisington-Lopez from the Center for Genome Sciences and Systems Biology at Washington University School of Medicine for her sequencing expertise. NR 65 TC 108 Z9 109 U1 15 U2 64 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 29 PY 2015 VL 160 IS 3 BP 447 EP 460 DI 10.1016/j.cell.2015.01.002 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CA8YX UT WOS:000349208000011 PM 25619688 ER PT J AU Francis, PA Regan, MM Fleming, GF Lang, I Ciruelos, E Bellet, M Bonnefoi, HR Climent, MA Da Prada, GA Burstein, HJ Martino, S Davidson, NE Geyer, CE Walley, BA Coleman, R Kerbrat, P Buchholz, S Ingle, JN Winer, EP Rabaglio-Poretti, M Maibach, R Ruepp, B Giobbie-Hurder, A Price, KN Colleoni, M Viale, G Coates, AS Goldhirsch, A Gelber, RD AF Francis, Prudence A. Regan, Meredith M. Fleming, Gini F. Lang, Istvan Ciruelos, Eva Bellet, Meritxell Bonnefoi, Herve R. Climent, Miguel A. Da Prada, Gian Antonio Burstein, Harold J. Martino, Silvana Davidson, Nancy E. Geyer, Charles E., Jr. Walley, Barbara A. Coleman, Robert Kerbrat, Pierre Buchholz, Stefan Ingle, James N. Winer, Eric P. Rabaglio-Poretti, Manuela Maibach, Rudolf Ruepp, Barbara Giobbie-Hurder, Anita Price, Karen N. Colleoni, Marco Viale, Giuseppe Coates, Alan S. Goldhirsch, Aron Gelber, Richard D. CA SOFT Investigators Int Breast Canc Study Grp TI Adjuvant Ovarian Suppression in Premenopausal Breast Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID YOUNG-WOMEN; CHEMOTHERAPY; THERAPY; TRIALS; METAANALYSIS; AMENORRHEA; TAMOXIFEN; GOSERELIN AB BACKGROUND Suppression of ovarian estrogen production reduces the recurrence of hormone-receptor-positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain. METHODS We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal. RESULTS After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87). CONCLUSIONS Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. C1 [Francis, Prudence A.] Univ Melbourne, St Vincents Hosp, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Francis, Prudence A.; Coates, Alan S.] Univ Newcastle, Australia & New Zealand Breast Canc Trials Grp, Newcastle, NSW 2300, Australia. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Regan, Meredith M.; Giobbie-Hurder, Anita; Gelber, Richard D.] Dana Farber Canc Inst, IBCSG, Ctr Stat, Boston, MA 02115 USA. [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Med, Boston, MA USA. [Burstein, Harold J.; Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Susan F Smith Ctr Womens Canc, Boston, MA 02115 USA. [Burstein, Harold J.; Winer, Eric P.] Alliance Clin Trials Oncol, Boston, MA USA. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, IBCSG Stat Ctr, Boston, MA USA. [Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Frontier Sci & Technol Res Fdn, Boston, MA 02115 USA. [Fleming, Gini F.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Fleming, Gini F.] Alliance Clin Trials Oncol, Chicago, IL USA. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Lang, Istvan] Int Breast Canc Study Grp, Budapest, Hungary. [Ciruelos, Eva] Univ Hosp 12 Octubre, Madrid, Spain. [Bellet, Meritxell] Vall dHebron Inst Oncol, Barcelona, Spain. [Bellet, Meritxell] Vall dHebron Univ Hosp, Barcelona, Spain. [Ciruelos, Eva; Bellet, Meritxell; Climent, Miguel A.] SOLTI Grp, Barcelona, Spain. [Climent, Miguel A.] Inst Valenciano Oncol, Valencia, Spain. [Bonnefoi, Herve R.] Univ Bordeaux, Inst Bergonie Comprehens Canc Ctr, INSERM, U916, Bordeaux, France. [Kerbrat, Pierre] Univ Rennes, Ctr Eugene Marquis, Rennes, France. [Bonnefoi, Herve R.; Kerbrat, Pierre] European Org Res Treatment Canc, Brussels, Belgium. [Da Prada, Gian Antonio] Salvatore Maugeri Fdn, Pavia, Italy. [Da Prada, Gian Antonio] IBCSG, Pavia, Italy. [Colleoni, Marco; Goldhirsch, Aron] Univ Milan, European Inst Oncol, Milan, Italy. [Colleoni, Marco; Goldhirsch, Aron] Univ Milan, Int Breast Canc Study Grp, Milan, Italy. [Viale, Giuseppe] Univ Milan, European Inst Oncol, IBCSG Cent Pathol Ctr, Milan, Italy. [Martino, Silvana] Angeles Clin, Santa Monica, CA USA. [Martino, Silvana] Res Inst, Santa Monica, CA USA. [Martino, Silvana] SWOG, Santa Monica, CA USA. [Davidson, Nancy E.] Univ Pittsburgh, Med Ctr, Inst Canc, Ctr Canc, Pittsburgh, PA USA. [Davidson, Nancy E.] ECOG ACRIN Canc Res Grp, Pittsburgh, PA USA. [Geyer, Charles E., Jr.] Virginia Commonwealth Univ, Massey Canc Ctr, Sch Med, Richmond, VA 23284 USA. [Geyer, Charles E., Jr.] NRG Oncol, Richmond, VA USA. [Walley, Barbara A.] Tom Baker Canc Clin, Calgary, AB, Canada. [Walley, Barbara A.] Natl Canc Inst Canada, Clin Trials Grp, Calgary, AB, Canada. [Coleman, Robert] Weston Pk Hosp, Sheffield, S Yorkshire, England. [Coleman, Robert] Natl Inst Canc Res, Breast Canc Clin Studies Grp, London, England. [Coleman, Robert] Inst Canc Res, Clin Trials & Stat Unit, London SW3 6JB, England. [Buchholz, Stefan] Univ Med Ctr Regensburg, German Breast Grp, Regensburg, Germany. [Buchholz, Stefan] Univ Med Ctr Regensburg, Dept Obstet & Gynecol, Regensburg, Germany. [Ingle, James N.] Mayo Clin, Rochester, MN USA. [Ingle, James N.] Alliance Clin Trials Oncol, Rochester, MN USA. [Rabaglio-Poretti, Manuela] Univ Bern, Inselspital, Univ Hosp, CH-3010 Bern, Switzerland. [Rabaglio-Poretti, Manuela; Maibach, Rudolf; Ruepp, Barbara] IBCSG Coordinating Ctr, Bern, Switzerland. RP Francis, PA (reprint author), Peter MacCallum Canc Ctr, Locked Bag 1,ABeckett St, Melbourne, Vic 8006, Australia. EM ibcsgcc@ibcsg.org OI Ciruelos, Eva /0000-0002-2796-1042 FU Pfizer FX Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690. NR 19 TC 135 Z9 145 U1 7 U2 45 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 29 PY 2015 VL 372 IS 5 BP 436 EP 446 DI 10.1056/NEJMoa1412379 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CA1CD UT WOS:000348649700008 PM 25495490 ER PT J AU Cooper, CM Baron, JM AF Cooper, Cynthia M. Baron, Jason M. TI Case 4-2015: A 49-Year-Old Man with Obtundation Followed by Agitation and Acidosis Ethylene glycol ingestion SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; ACUTE MYOCARDIAL-INFARCTION; GAP METABOLIC-ACIDOSIS; SUICIDAL IDEATION; RESPIRATORY RATE; ANION-GAP; META-CHLOROPHENYLPIPERAZINE; PHARMACODYNAMIC PROFILE; VENLAFAXINE OVERDOSE; OSMOLAL GAP C1 [Cooper, Cynthia M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02163 USA. [Baron, Jason M.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cooper, Cynthia M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Baron, Jason M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cooper, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02163 USA. NR 52 TC 1 Z9 1 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 29 PY 2015 VL 372 IS 5 BP 465 EP 473 DI 10.1056/NEJMcpc1410940 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CA1CD UT WOS:000348649700012 PM 25629745 ER PT J AU Solomon, CG Greene, MF AF Solomon, Caren G. Greene, Michael F. TI Control of Hypertension in Pregnancy - If Some Is Good, Is More Worse? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Solomon, Caren G.; Greene, Michael F.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Solomon, CG (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 8 TC 4 Z9 5 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 29 PY 2015 VL 372 IS 5 BP 475 EP 476 DI 10.1056/NEJMe1414836 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CA1CD UT WOS:000348649700013 PM 25629746 ER PT J AU Morris, H DeWolf, S Robins, H Sprangers, B LoCascio, SA Shonts, BA Kawai, T Wong, WC Yang, SX Zuber, J Shen, YF Sykes, M AF Morris, Heather DeWolf, Susan Robins, Harlan Sprangers, Ben LoCascio, Samuel A. Shonts, Brittany A. Kawai, Tatsuo Wong, Waichi Yang, Suxiao Zuber, Julien Shen, Yufeng Sykes, Megan TI Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID BONE-MARROW-TRANSPLANTATION; MISMATCHED RENAL-TRANSPLANTATION; MAINTENANCE IMMUNOSUPPRESSION; MEDIATED LYMPHOLYSIS; MIXED CHIMERISM; IN-VIVO; INDUCTION; RECIPIENTS; REJECTION; REGIMEN AB T cell responses to allogeneic major histocompatibility complex antigens present a formidable barrier to organ transplantation, necessitating long-term immunosuppression to minimize rejection. Chronic rejection and drug-induced morbidities are major limitations that could be overcome by allograft tolerance induction. Tolerance was first intentionally induced in humans via combined kidney and bone marrow transplantation (CKBMT), but the mechanisms of tolerance in these patients are incompletely understood. We now establish an assay to identify donor-reactive T cells and test the role of deletion in tolerance after CKBMT. Using high-throughput sequencing of the T cell receptor B chain CDR3 region, we define a fingerprint of the donor-reactive T cell repertoire before transplantation and track those clones after transplant. We observed posttransplant reductions in donor-reactive T cell clones in three tolerant CKBMT patients; such reductions were not observed in a fourth, nontolerant, CKBMT patient or in two conventional kidney transplant recipients on standard immunosuppressive regimens. T cell repertoire turnover due to lymphocyte-depleting conditioning only partially accounted for the observed reductions in tolerant patients; in fact, conventional transplant recipients showed expansion of circulating donor-reactive clones, despite extensive repertoire turnover. Moreover, loss of donor-reactive T cell clones more closely associated with tolerance induction than in vitro functional assays. Our analysis supports clonal deletion as a mechanism of allograft tolerance in CKBMT patients. The results validate the contribution of donor-reactive T cell clones identified before transplant by our method, supporting further exploration as a potential biomarker of transplant outcomes. C1 [Morris, Heather; DeWolf, Susan; Sprangers, Ben; LoCascio, Samuel A.; Shonts, Brittany A.; Wong, Waichi; Yang, Suxiao; Zuber, Julien; Shen, Yufeng; Sykes, Megan] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Robins, Harlan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Kawai, Tatsuo] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shen, YF (reprint author), Columbia Univ, Med Ctr, New York, NY 10032 USA. EM ys2411@columbia.edu; megan.sykes@columbia.edu FU NIH grant ROI [AI084074]; NIH grant PO1 [P01 AI106697]; ITN [N01 AI15416]; Kidney Research Student Scholar Grant from the American Society of Nephrology; NIH [S10RR027050] FX The work was supported in part by NIH grants ROI #AI084074, PO1 grant #P01 AI106697, and ITN contract N01 AI15416. S.D.W. was supported by a Kidney Research Student Scholar Grant from the American Society of Nephrology. FACS instrumentation was purchased with NIH grant #S10RR027050. NR 38 TC 34 Z9 34 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 28 PY 2015 VL 7 IS 272 AR 272ra10 DI 10.1126/scitranslmed.3010760 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CB1YA UT WOS:000349422700001 PM 25632034 ER PT J AU Haridas, V Pean, P Jasenosky, LD Madec, Y Laureillard, D Sok, T Sath, S Borand, L Marcy, O Chan, S Tsitsikov, E Delfraissy, JF Blanc, FX Goldfeld, AE AF Haridas, Viraga Pean, Polidy Jasenosky, Luke D. Madec, Yoann Laureillard, Didier Sok, Thim Sath, Sun Borand, Laurence Marcy, Olivier Chan, Sarin Tsitsikov, Erdyni Delfraissy, Jean-Francois Blanc, Francois-Xavier Goldfeld, Anne E. CA CAPRI-T ANRS 121614 Study Team TI TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in highly immunosuppressed HIV-infected patients with TB SO AIDS LA English DT Article DE activated T cells; antiretroviral therapy; CAMELIA trial; CCR5(+)CD4(+); effector memory; HIV; immunosuppression; T cells; TB; TB-IRIS ID RECONSTITUTION INFLAMMATORY SYNDROME; IMMUNE-RESTORATION-DISEASE; ANTIRETROVIRAL THERAPY; TUBERCULOSIS; EXPRESSION; INITIATION; RESPONSES; CCR5; LYMPHOCYTES; SUBSETS AB Objective: To investigate the impact of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) upon immunological recovery and the T-cell compartment after initiation of TB and antiretroviral therapy (ART). Design and methods: We prospectively evaluated T-cell immunophenotypes by flow cytometry and cytokines by Luminex assays in a subset (n = 154) of highly immunosuppressed HIV-infected patients with TB from the Cambodian Early versus Late Introduction of Antiretrovirals randomized clinical trial. We compared findings from patients who developed TB-IRIS with findings from patients who did not develop TB-IRIS. Data were evaluated with mixed-effect linear regression, Kaplan-Meier estimates, and Wilcoxon rank-sum tests, and q-values were calculated to control for multiple comparisons. Results: Development of TB-IRIS was associated with significantly greater pre-ART frequencies of HLA-DR(+)CD45RO(+)CD4(+), CCR5(+)CD4(+), OX40(+)CD4(+)and Fas(+) effector memory CD8(+) T cells, and significantly elevated levels of plasma interleukin (IL)-6, IL-1 beta, IL-8, and IL-10, and viral load. Post-ART initiation, effector memory CD4(+) and Fas(+) effector memory CD4(+) T-cell frequencies significantly expanded, and central memory CD4(+) T-cell frequencies significantly contracted in patients who experienced TB-IRIS. By week 34 post-TB treatment initiation, effector memory/central memory CD4(+) T-cell ratios were markedly higher in TB-IRIS versus non-TB-IRIS patients. Conclusions: A distinct pattern of pre-ART T-cell and cytokine markers appear to poise the immune response of certain patients to develop TB-IRIS. Experience of TB-IRIS is then associated with long-term remodeling of the CD4(+) T-cell memory compartment towards an effector memory-dominated phenotype. We speculate that these pre and post-ART TB-IRIS-associated immune parameters may contribute to superior immune control of TB/HIV co-infection and better clinical outcome. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Haridas, Viraga; Jasenosky, Luke D.; Goldfeld, Anne E.] Harvard Univ, Boston Childrens Hosp, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. [Pean, Polidy] Inst Pasteur Cambodge, Phnom Penh, Cambodia. [Madec, Yoann] Inst Pasteur, Emerging Dis Epidemiol Unit, Paris, France. [Laureillard, Didier; Sok, Thim; Sath, Sun; Marcy, Olivier; Chan, Sarin; Goldfeld, Anne E.] Cambodian Hlth Comm, Phnom Penh, Cambodia. [Borand, Laurence] Inst Pasteur Cambodge, Epidemiol & Publ Hlth Unit, Phnom Penh, Cambodia. [Tsitsikov, Erdyni] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Lab Med, Boston, MA USA. [Delfraissy, Jean-Francois] French Natl Agcy Res AIDS & Viral Hepatitis ANRS, Paris, France. [Delfraissy, Jean-Francois; Blanc, Francois-Xavier] Hop Bicetre, AP HP, Le Kremlin Bicetre, France. RP Goldfeld, AE (reprint author), Harvard Univ, Boston Childrens Hosp, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. EM anne.goldfeld@childrens.harvard.edu RI Blanc, Francois-Xavier/D-7425-2015 FU ANRS [12164]; NIH [R21AI076023]; Annenberg Foundation; AERAS; AmFAR; NIAID/NIH-IeDEA [U01AI069907-07] FX The authors are indebted to Wallis Annenberg whose generosity made this study possible, and to John Moores for his generous gift. This work was supported by grants from the ANRS (12164), the NIH (R21AI076023), the Annenberg Foundation, AERAS, and AmFAR, with support from NIAID/NIH-IeDEA (U01AI069907-07), and a gift from John Moores. We are grateful to Francoise Barre-Sinoussi for her help, advice, and support over the years. We thank Eric Nerrienet, Claire Rekacewicz, Daniel Scott, Gianfranco Pancino, Jean-Louis Sarthou, and Charles Mayaud for helpful discussions and advice as we began the study, and Jean-Louis Sarthou for his long time support of the Harvard team's collaboration with the Institut Pasteur du Cambodge. We thank the CAMELIA study team, including the site nurses, doctors, and health workers, and Vincent Deubel and the staff at the Institut Pasteur du Cambodge. We thank Larry Fox, Rod Hoff, Jane Bupp, and Brigitte Bazin for their support and helpful discussions from the beginning of CAMELIA onward and the staff of the Cambodian Health Committee, especially Sam Sophan, for his contributions to and support of the work. We thank Leslie Kalish of Children's Hospital Boston and the Harvard Catalyst Biostatistical Consulting program (NIH UL1 TR001102) for expert statistical advice and help as we started the analysis. We also thank Jerry Sadoff for his early support and Judy Lieberman for helpful comments on the manuscript. Finally, we are deeply indebted to the patients who took part in this study, who generously offered their participation to help the scientific community find solutions to AIDS and TB. NR 49 TC 6 Z9 6 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 28 PY 2015 VL 29 IS 3 BP 263 EP 273 DI 10.1097/QAD.0000000000000546 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AZ0SZ UT WOS:000347956200002 PM 25486415 ER PT J AU Denison, JA Koole, O Tsui, S Menten, J Torpey, K van Praag, E Mukadi, YD Colebunders, R Auld, AF Agolory, S Kaplan, JE Mulenga, M Kwesigabo, GP Wabwire-Mangen, F Bangsberg, DR AF Denison, Julie A. Koole, Olivier Tsui, Sharon Menten, Joris Torpey, Kwasi van Praag, Eric Mukadi, Ya Diul Colebunders, Robert Auld, Andrew F. Agolory, Simon Kaplan, Jonathan E. Mulenga, Modest Kwesigabo, Gideon P. Wabwire-Mangen, Fred Bangsberg, David R. TI Incomplete adherence among treatment-experienced adults on antiretroviral therapy in Tanzania, Uganda and Zambia SO AIDS LA English DT Article DE antiretroviral therapy; HIV/AIDS; medication adherence; sub-Saharan Africa; Tanzania; Uganda; Zambia ID SUB-SAHARAN AFRICA; SELF-REPORTED ADHERENCE; HIV-INFECTED PATIENTS; HIGH-INCOME COUNTRIES; MEDICATION ADHERENCE; VIROLOGICAL RESPONSE; CLINICAL-TRIALS; SOCIAL SUPPORT; NORTH-AMERICA; RURAL UGANDA AB Objectives: To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa. Design: A cross-sectional study. Methods: Systematically selected ART clients (>= 18 years; on ART >= 6 months) attending 18facilities in three countries (250 clients/facility) were interviewed. Client self-reports (3-day, 30-day, Case Index >= 48 consecutive hours of missed ART), healthcare provider estimates and the pharmacymedication possession ratio(MPR) were used to estimate ART adherence. Participants from two facilities per country underwent HIV RNA testing. Optimal adherence measures were selected on the basis of degree of association with concurrent HIV RNA dichotomized at less than or greater/equal to 1000 copies/ml. Multivariate regression analysis, adjusted for site-level clustering, assessed associations between incomplete adherence and individual and programme factors. Results: A total of 4489 participants were included, of whom 1498 underwent HIV RNA testing. Nonadherence ranged from 3.2% missing at least 48 consecutive hours to 40.1% having an MPR of less than 90%. The percentage with HIV RNA at least 1000 copies/ml ranged from 7.2 to 17.2% across study sites (mean = 9.9%). Having at least 48 consecutive hours of missed ART was the adherence measure most strongly related to virologic failure. Factors significantly related to incomplete adherence included visiting a traditional healer, screening positive for alcohol abuse, experiencing more HIV symptoms, having an ART regimen without nevirapine and greater levels of internalized stigma. Conclusion: Results support more in-depth investigations of the role of traditional healers, and the development of interventions to address alcohol abuse and internalized stigma among treatment-experienced adult ART patients. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Denison, Julie A.; Tsui, Sharon; Torpey, Kwasi; van Praag, Eric; Mukadi, Ya Diul] FHI 360, Social & Behav Hlth Sci, Durham, NC USA. [Denison, Julie A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. [Koole, Olivier; Menten, Joris; Colebunders, Robert] Inst Trop Med, B-2000 Antwerp, Belgium. [Koole, Olivier] London Sch Hyg & Trop Med, London WC1, England. [Colebunders, Robert] Univ Antwerp, B-2020 Antwerp, Belgium. [Auld, Andrew F.; Agolory, Simon; Kaplan, Jonathan E.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Mulenga, Modest] Trop Dis Res Ctr, Ndola, Zambia. [Kwesigabo, Gideon P.] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Wabwire-Mangen, Fred] Makerere Univ, Coll Hlth Sci, Infect Dis Inst, Kampala, Uganda. [Bangsberg, David R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Denison, JA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, 615 N Wolfe St,E5032, Baltimore, MD 21205 USA. EM jdenison@jhu.edu OI Auld, Andrew/0000-0001-5089-9163 FU President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC); Health Resources & Services Administration (HRSA) [2006-N-08428]; FHI [360] FX This research has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) and the Health Resources & Services Administration (HRSA) under the terms of the contract no. 2006-N-08428 with FHI 360. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of CDC, HRSA or any other federal agency or office. NR 65 TC 10 Z9 10 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 28 PY 2015 VL 29 IS 3 BP 361 EP 371 DI 10.1097/QAD.0000000000000543 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AZ0SZ UT WOS:000347956200012 PM 25686684 ER PT J AU Friel, AM Zhang, L Pru, CA Clark, NC McCallum, ML Blok, LJ Shioda, T Peluso, JJ Rueda, BR Pru, JK AF Friel, Anne M. Zhang, Ling Pru, Cindy A. Clark, Nicole C. McCallum, Melissa L. Blok, Leen J. Shioda, Toshi Peluso, John J. Rueda, Bo R. Pru, James K. TI Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors SO CANCER LETTERS LA English DT Article DE Cancer; Chemotherapy; Endometrial; PGRMC1; Progesterone; Xenograft ID IMMORTALIZED GRANULOSA-CELLS; RNA-BINDING-PROTEIN; OVARIAN-CANCER; ANTIAPOPTOTIC ACTION; HORMONAL-THERAPY; GENE-EXPRESSION; PGRMC1; BREAST; CARCINOMA; VIABILITY AB Endometrial cancer is the leading gynecologic cancer in women in the United States with 52,630 women predicted to be diagnosed with the disease in 2014. The objective of this study was to determine if progesterone (P4) receptor membrane component 1 (PGRMC1) influenced endometrial cancer cell viability in response to chemotherapy in vitro and in vivo. A lentiviral-based shRNA knockdown approach was used to generate stable PGRMC1-intact and PGRMC1-deplete Ishikawa endometrial cancer cell lines that also lacked expression of the classical progesterone receptor (PGR). Progesterone treatment inhibited mitosis of PGRMC1-intact, but not PGRMC1-deplete cells, suggesting that PGRMC1 mediates the anti-mitotic actions of P4. To test the hypothesis that PGRMC1 attenuates chemotherapy-induced apoptosis, PGRMC1-intact and PGRMC1-deplete cells were treated in vitro with vehicle, P4 (1 mu M), doxorubicin (Dox, 2 mu g/ml), or P4 + Dox for 48 h. Doxorubicin treatment of PGRMC1-intact cells resulted in a significant increase in cell death; however, co-treatment with P4 significantly attenuated Dox-induced cell death. This response to P-4 was lost in PGRMC1-deplete cells. To extend these observations in vivo, a xenograft model was employed where PGRMC1-intact and PGRMC1-deplete endometrial tumors were generated following subcutaneous and intraperitoneal inoculation of immunocompromised NOD/SCID and nude mice, respectively. Tumors derived from PGRMC1-deplete cells grew slower than tumors from PGRMC1-intact cells. Mice harboring endometrial tumors were then given three treatments of vehicle (1:1 cremophor EL: ethanol + 0.9% saline) or chemotherapy [Paditaxel (15 mg/kg, i.p.) followed after an interval of 30 minutes by CARBOplatin (50 mg/kg)] at five day intervals. In response to chemotherapy, tumor volume decreased approximately four-fold more in PGRMC1-deplete tumors when compared with PGRMC1-intact control tumors, suggesting that PGRMC1 promotes tumor cell viability during chemotherapeutic stress. In sum, these in Vitro and in vivo findings demonstrate that PGRMC1 plays a prominent role in the growth and chemoresistance of human endometrial tumors. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Friel, Anne M.; Zhang, Ling; Shioda, Toshi; Rueda, Bo R.] Harvard Univ, Sch Med, Vincent Ctr Reprod Biol,Ctr Canc Res, Dept Obstet & Gynecol,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pru, Cindy A.; McCallum, Melissa L.; Pru, James K.] Washington State Univ, Dept Anim Sci, Pullman, WA 99164 USA. [Clark, Nicole C.; Pru, James K.] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. [Blok, Leen J.] Erasmus Univ, Med Ctr, Josephine Nefkens Inst, Dept Obstet & Gynecol, Rotterdam, Netherlands. [Rueda, Bo R.] Univ Connecticut, Ctr Hlth, Dept Obstet, Farmington, CT 06030 USA. [Peluso, John J.] Univ Connecticut, Ctr Hlth, Dept Gynecol, Farmington, CT 06030 USA. [Peluso, John J.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06030 USA. RP Pru, JK (reprint author), Washington State Univ, Dept Anim Sci, Pullman, WA 99164 USA. EM jpru@wsu.edu FU Vincent Memorial Research Funds; Advanced Medical Research Foundation; NIH [RR030264, OD016564] FX This work was supported by Vincent Memorial Research Funds, the Advanced Medical Research Foundation, and NIH RR030264 and OD016564. NR 58 TC 10 Z9 10 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD JAN 28 PY 2015 VL 356 IS 2 BP 434 EP 442 DI 10.1016/j.canlet.2014.09.036 PN B PG 9 WC Oncology SC Oncology GA AZ1NL UT WOS:000348005500013 PM 25304370 ER PT J AU Wong, WP AF Wong, Wesley P. TI Revealing the Mechanical Regulation of Hemostasis with Novel Approaches in Single-Molecule Manipulation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Wong, Wesley P.] Harvard Univ, Wyss Inst, Biol Chem & Mol Pharmacol, Cambridge, MA 02138 USA. [Wong, Wesley P.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 35-Subg BP 7A EP 7A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700036 ER PT J AU Song, LK Sun, ZYJ Kim, M Kaur, P Wagner, G Reinherz, EL AF Song, Likai Sun, Zhen-Yu J. Kim, Mikyung Kaur, Pavanjeet Wagner, Gerhard Reinherz, Ellis L. TI HIV gp41-Antibody Interaction at the Viral Membrane Interface Defined by EPR Spectroscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Song, Likai; Kaur, Pavanjeet] Natl High Magnet Field Lab, Tallahassee, FL USA. [Song, Likai; Kaur, Pavanjeet] Florida State Univ, Tallahassee, FL 32306 USA. [Sun, Zhen-Yu J.; Kim, Mikyung; Wagner, Gerhard; Reinherz, Ellis L.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Mikyung; Reinherz, Ellis L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 188-Plat BP 38A EP 39A PG 2 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700189 ER PT J AU Kovacs-Bogdan, E Sancak, Y Kamer, KJ Plovanich, M Jambhekar, A Huber, RJ Myre, MA Blower, MD Mootha, VK AF Kovacs-Bogdan, Erika Sancak, Yasemin Kamer, Kimberli J. Plovanich, Molly Jambhekar, Ashwini Huber, Robert J. Myre, Michael A. Blower, Michael D. Mootha, Vamsi K. TI In vivo Reconstitution of the Mitochondrial Uniporter SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kovacs-Bogdan, Erika; Sancak, Yasemin; Kamer, Kimberli J.; Plovanich, Molly; Jambhekar, Ashwini; Blower, Michael D.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Mol Biol, Boston, MA 02114 USA. [Huber, Robert J.; Myre, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 894-Plat BP 177A EP 178A PG 2 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100104 ER PT J AU Kamer, KJ Mootha, VK AF Kamer, Kimberli J. Mootha, Vamsi K. TI MICU1 and MICU2 Operate Together to Regulate the Uniporter SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Kamer, Kimberli J.] Harvard Univ, Chem & Chem Biol, Cambridge, MA 02138 USA. [Mootha, Vamsi K.] Massachusetts Gen Hosp, HHMI, Mol Biol, Boston, MA 02114 USA. [Mootha, Vamsi K.] Harvard Univ, Sch Med, Syst Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2870-Pos BP 567A EP 567A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600478 ER PT J AU Zamani, P Rawat, D Shiva-Kumar, P Geraci, S Bhuva, R Konda, P Doulias, PT Ischiropoulos, H Townsend, RR Margulies, KB Cappola, TP Poole, DC Chirinos, JA AF Zamani, Payman Rawat, Deepa Shiva-Kumar, Prithvi Geraci, Salvatore Bhuva, Rushik Konda, Prasad Doulias, Paschalis-Thomas Ischiropoulos, Harry Townsend, Raymond R. Margulies, Kenneth B. Cappola, Thomas P. Poole, David C. Chirinos, Julio A. TI Effect of Inorganic Nitrate on Exercise Capacity in Heart Failure With Preserved Ejection Fraction SO CIRCULATION LA English DT Article DE exercise; heart failure; nitrates; nitric oxide ID NEAR-INFRARED SPECTROSCOPY; SOCIETY-OF-CARDIOLOGY; O-2 UPTAKE KINETICS; DIETARY NITRATE; SKELETAL-MUSCLE; NITRIC-OXIDE; OXIDATIVE CAPACITY; INTENSITY EXERCISE; OXYGEN-CONSUMPTION; WAVE REFLECTIONS AB Background-Inorganic nitrate (NO3-), abundant in certain vegetables, is converted to nitrite by bacteria in the oral cavity. Nitrite can be converted to nitric oxide in the setting of hypoxia. We tested the hypothesis that NO3- supplementation improves exercise capacity in heart failure with preserved ejection fraction via specific adaptations to exercise. Methods and Results-Seventeen subjects participated in this randomized, double-blind, crossover study comparing a single dose of NO3- rich beetroot juice (NO3-, 12.9 mmol) with an identical nitrate-depleted placebo. Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests, with measurements of cardiac output and skeletal muscle oxygenation. We also assessed skeletal muscle oxidative function. Study end points included exercise efficiency (total work/total oxygen consumed), peak Vo(2), total work performed, vasodilatory reserve, forearm mitochondrial oxidative function, and augmentation index (a marker of arterial wave reflections, measured via radial arterial tonometry). Supplementation increased plasma nitric oxide metabolites (median, 326 versus 10 mu mol/L; P=0.0003), peak (V) over doto(2) (12.6 +/- 3.7 versus 11.6 +/- 3.1 mL O-2.min(-1).kg(-1); P=0.005), and total work performed (55.6 +/- 35.3 versus 49.2 +/- 28.9 kJ; P=0.04). However, efficiency was unchanged. NO3- led to greater reductions in systemic vascular resistance (-42.4 +/- 16.6% versus -31.8 +/- 20.3%; P=0.03) and increases in cardiac output (121.2 +/- 59.9% versus 88.7 +/- 53.3%; P=0.006) with exercise. NO3- reduced aortic augmentation index (132.2 +/- 16.7% versus 141.4 +/- 21.9%; P=0.03) and tended to improve mitochondrial oxidative function. Conclusions-NO3- increased exercise capacity in heart failure with preserved ejection fraction by targeting peripheral abnormalities. Efficiency did not change as a result of parallel increases in total work and (V)over doto(2). NO3- increased exercise vasodilatory and cardiac output reserves. NO3- also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling. C1 [Zamani, Payman; Shiva-Kumar, Prithvi; Konda, Prasad; Margulies, Kenneth B.; Cappola, Thomas P.; Chirinos, Julio A.] Hosp Univ Penn, Perelman Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Rawat, Deepa; Shiva-Kumar, Prithvi; Geraci, Salvatore; Bhuva, Rushik; Chirinos, Julio A.] Philadelphia Vet Affairs Med Ctr, Div Cardiol, Philadelphia, PA USA. [Doulias, Paschalis-Thomas; Ischiropoulos, Harry] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA. [Townsend, Raymond R.] Univ Penn, Perelman Sch Med, Div Nephrol Hypertens, Philadelphia, PA 19104 USA. [Poole, David C.] Kansas State Univ, Dept Kinesiol, Manhattan, KS 66506 USA. [Poole, David C.] Kansas State Univ, Dept Anat, Manhattan, KS 66506 USA. [Poole, David C.] Kansas State Univ, Dept Physiol, Manhattan, KS 66506 USA. RP Chirinos, JA (reprint author), 3800 Woodland Ave,Room 8B111, Philadelphia, PA 19104 USA. EM Julio.Chirinos@uphs.upenn.edu FU Gilead Life Sciences; Atcor Medical; Cardiodynamics; APC Cardiovascular; National Institutes of Health [HL54926, HL105993, HL110338, HL113777]; Juventis Therapeutics; Celladon Corp; Thoratec Corp; Innolign Biomedical, LLC FX Dr Zamani performed prior research in HFpEF that was funded by Gilead Life Sciences. Dr Chirinos is named as inventor in a patent application for the use of inorganic nitrate in HFpEF. Dr Chirinos has received minor support (equipment loans) from Atcor Medical, Cardiodynamics, and APC Cardiovascular. Dr Ischiropoulos is the Gisela and Dennis Alter Chair in Pediatric Neonatology at the Children's Hospital of Philadelphia and is supported by National Institutes of Health grant HL54926. Dr Margulies reports advisory committee membership for Novo Nordisk and AstraZeneca, as well as research grant support from Juventis Therapeutics, Celladon Corp, Thoratec Corp, Innolign Biomedical, LLC, and the National Institutes of Health (HL105993, HL110338, HL113777). The other authors report no conflicts. NR 54 TC 57 Z9 59 U1 6 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 27 PY 2015 VL 131 IS 4 BP 371 EP U1184 DI 10.1161/CIRCULATIONAHA.114.012957 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AZ7YR UT WOS:000348432100014 PM 25533966 ER PT J AU Mozaffarian, D Benjamin, EJ Go, AS Arnett, DK Blaha, MJ Cushman, M de Ferranti, S Despres, JP Fullerton, HJ Howard, VJ Huffman, MD Judd, SE Kissela, BM Lackland, DT Lichtman, JH Lisabeth, LD Liu, SM Mackey, RH Matchar, DB McGuire, DK Mohler, ER Moy, CS Muntner, P Mussolino, ME Nasir, K Neumar, RW Nichol, G Palaniappan, L Pandey, DK Reeves, MJ Rodriguez, CJ Sorlie, PD Stein, J Towfighi, A Turan, TN Virani, SS Willey, JZ Woo, D Yeh, RW Turner, MB AF Mozaffarian, Dariush Benjamin, Emelia J. Go, Alan S. Arnett, Donna K. Blaha, Michael J. Cushman, Mary de Ferranti, Sarah Despres, Jean-Pierre Fullerton, Heather J. Howard, Virginia J. Huffman, Mark D. Judd, Suzanne E. Kissela, Brett M. Lackland, Daniel T. Lichtman, Judith H. Lisabeth, Lynda D. Liu, Simin Mackey, Rachel H. Matchar, David B. McGuire, Darren K. Mohler, Emile R., III Moy, Claudia S. Muntner, Paul Mussolino, Michael E. Nasir, Khurram Neumar, Robert W. Nichol, Graham Palaniappan, Latha Pandey, Dilip K. Reeves, Mathew J. Rodriguez, Carlos J. Sorlie, Paul D. Stein, Joel Towfighi, Amytis Turan, Tanya N. Virani, Salim S. Willey, Joshua Z. Woo, Daniel Yeh, Robert W. Turner, Melanie B. CA Amer Heart Assoc Stat Comm Stroke Stat Subcomm TI Executive Summary: Heart Disease and Stroke Statistics-2015 Update A Report From the American Heart Association SO CIRCULATION LA English DT Article C1 [Mozaffarian, Dariush] Tufts Univ, Medford, MA 02155 USA. [Arnett, Donna K.; Howard, Virginia J.; Judd, Suzanne E.; Muntner, Paul] Univ Alabama Birmingham, Birmingham, AL USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Blaha, Michael J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Cushman, Mary] Univ Vermont, Burlington, VT 05405 USA. [de Ferranti, Sarah] Childrens Hosp Boston, Boston, MA USA. [Despres, Jean-Pierre] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada. [Fullerton, Heather J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Go, Alan S.] Kaiser Permanente, Oakland, CA USA. [Huffman, Mark D.] Northwestern Univ, Evanston, IL 60208 USA. [Kissela, Brett M.] Univ Cincinnati, Acad Hlth Ctr, Cincinnati, OH 45221 USA. [Lackland, Daniel T.; Turan, Tanya N.] Med Univ S Carolina, Charleston, SC USA. [Lichtman, Judith H.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Lisabeth, Lynda D.; Neumar, Robert W.] Univ Michigan, Ann Arbor, MI 48109 USA. [Liu, Simin] Brown Univ, Providence, RI 02912 USA. [Mackey, Rachel H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Matchar, David B.] Duke Univ, Durham, NC 27706 USA. [McGuire, Darren K.] Univ Texas Southwestern Med Ctr, Houston, TX USA. [Mohler, Emile R., III] Univ Penn, Philadelphia, PA 19104 USA. [Moy, Claudia S.; Mussolino, Michael E.] NIH, Washington, DC USA. [Nasir, Khurram] Baptist Hlth Med Grp, New York, NY USA. [Nichol, Graham] Univ Washington, Seattle, WA 98195 USA. [Palaniappan, Latha] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Pandey, Dilip K.] Univ Illinois, Chicago, IL USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Rodriguez, Carlos J.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Sorlie, Paul D.] NHLBI, Washington, DC USA. [Stein, Joel; Willey, Joshua Z.] Columbia Univ, New York, NY 10027 USA. [Towfighi, Amytis] Univ So Calif, Los Angeles, CA 90089 USA. [Turner, Melanie B.] Amer Heart Assoc, Bethesda, MD USA. [Virani, Salim S.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Innovat, Methodist DeBakey Heart & Vasc Ctr,Michael E DeBa, Houston, TX 77030 USA. [Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mozaffarian, D (reprint author), Tufts Univ, Medford, MA 02155 USA. OI Mackey, Rachel/0000-0001-6088-2664; Turan, Tanya/0000-0001-5399-8845; Huffman, Mark/0000-0001-7412-2519; Benjamin, Emelia/0000-0003-4076-2336; Virani, Salim/0000-0001-9541-6954; Kissela, Brett/0000-0002-9773-4013 FU NIH/NHLBI; Canadian Institutes of Health Research (CIHR); European Foundation for the Study of Diabetes (EFSD); Fondation de l'IUCPQ; Canadian Partnership Against Cancer (CPAC); Heart & Stroke Foundation of Canada (HSFC); Fonds de la recherche en sante du Quebec; Heart and Stroke Foundation of Canada (HSFC); Diabete Quebec; Ministere de la Sante et des Services sociaux du Quebec; Ministere des Finances et de l'Economie du Quebec; Conseil franco-quebecois de cooperation universitaire (CFQCU); Astra-Zeneca; NHLBI; National Institute of Diabetes, Digestive and Kidney Diseases; Sanofi; World Heart Federation; JR Alberts Foundation; Eisenberg Foundation; Stanford University; GlaxoSmithKline; Takeda; Orexigen; Janssen; Eli Lilly; Bristol Myers Squibb; AstraZeneca; Boehringer Ingelheim; Merck; Novo Nordisk; Lexicon; Amgen Inc.; Nexstim; Tyromotion; Myomo; Department of Veterans Affairs; American Heart Association; American Diabetes Association; NIH FX Emelia J. Benjamin Boston University School of Medicine NIH/NHLBI dagger None None None None AHA, Circulation Associate Editor dagger None; Jean-Pierre Despres Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Quebec Canadian Institutes of Health Research (CIHR)dagger; European Foundation for the Study of Diabetes (EFSD)dagger; Fondation de l'IUCPQ dagger; Fondation de l'IUCPQ dagger; Canadian Partnership Against Cancer (CPAC) and Heart & Stroke Foundation of Canada (HSFC)dagger; Canadian Institutes of Health Research (CIHR)dagger; Canadian Institutes of Health Research (CIHR)dagger; Canadian Institutes of Health Research (CIHR)dagger; Fonds de la recherche en sante du Quebec dagger; Canadian Institutes of Health Research (CIHR)dagger; Canadian Institutes of Health Research (CIHR)dagger; Heart and Stroke Foundation of Canada (HSFC)dagger; Canadian Institutes of Health Research (CIHR)dagger; Canadian Institutes of Health Research (CIHR)dagger; Diabete Quebec*; Ministere de la Sante et des Services sociaux du Quebec dagger; Ministere des Finances et de l'Economie du Quebec dagger; Conseil franco-quebecois de cooperation universitaire (CFQCU)dagger; Heart and Stroke Foundation of Canada (HSFC)dagger; Heart and Stroke Foundation of Canada (HSFC)dagger; Heart and Stroke Foundation of Canada (HSFC)dagger None Pfizer Canada dagger; Merck dagger None None Abbott Laboratories dagger; Torrent Pharmaceuticals dagger None; Alan S. Go Kaiser Permanente Astra-Zeneca dagger; NHLBI dagger; National Institute of Diabetes, Digestive and Kidney Diseases dagger; Sanofi dagger None None None None None None; Mark D. Huffman Northwestern University World Heart Federation dagger; JR Alberts Foundation dagger; Eisenberg Foundation dagger None None None None None None; Simin Liu Brown University Stanford University dagger None None None None None None; Darren K. McGuire University of Texas-Southwestern Med Ctr GlaxoSmithKline*; Takeda*; Orexigen dagger; Janssen dagger; Eli Lilly*; Bristol Myers Squibb dagger; AstraZeneca dagger; Boehringer Ingelheim dagger; Merck dagger; Novo Nordisk dagger; Lexicon dagger None None Takeda dagger None Novo Nordisk dagger; Boehringer Ingelheim dagger; Merck*; Regeneron* None; Paul Muntner University of Alabama at Birmingham Amgen Inc. (research grant to study cardiovascular disease prevention, diagnosis and treatment)dagger None None None None None None; Joel Stein Columbia University Nexstim*; Tyromotion*; Myomo* None None None None Myomo* None; Salim S. Virani Michael E. DeBakey VA Medical Center Health Services Research and Development Center for Innovations, Baylor College of Medicine, Michael E. DeBakey VAMC, Methodist DeBakey Heart and Vascular Center Department of Veterans Affairs dagger; American Heart Association dagger; American Diabetes Association dagger None None None None None None; Joshua Z. Willey Columbia University NIH dagger None None None None None None NR 0 TC 80 Z9 84 U1 5 U2 73 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 27 PY 2015 VL 131 IS 4 BP 434 EP 441 DI 10.1161/CIR.0000000000000157 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AZ7YR UT WOS:000348432100023 ER PT J AU Mozaffarian, D Benjamin, EJ Go, AS Arnett, DK Blaha, MJ Cushman, M de Ferranti, S Despres, JP Fullerton, HJ Howard, VJ Huffman, MD Judd, SE Kissela, BM Lackland, DT Lichtman, JH Lisabeth, LD Liu, SM Mackey, RH Matchar, DB McGuire, DK Mohler, ER Moy, CS Muntner, P Mussolino, ME Nasir, K Neumar, RW Nichol, G Palaniappan, L Pandey, DK Reeves, MJ Rodriguez, CJ Sorlie, PD Stein, J Towfighi, A Turan, TN Virani, SS Willey, JZ Woo, D Yeh, RW Turner, MB AF Mozaffarian, Dariush Benjamin, Emelia J. Go, Alan S. Arnett, Donna K. Blaha, Michael J. Cushman, Mary de Ferranti, Sarah Despres, Jean-Pierre Fullerton, Heather J. Howard, Virginia J. Huffman, Mark D. Judd, Suzanne E. Kissela, Brett M. Lackland, Daniel T. Lichtman, Judith H. Lisabeth, Lynda D. Liu, Simin Mackey, Rachel H. Matchar, David B. McGuire, Darren K. Mohler, Emile R., III Moy, Claudia S. Muntner, Paul Mussolino, Michael E. Nasir, Khurram Neumar, Robert W. Nichol, Graham Palaniappan, Latha Pandey, Dilip K. Reeves, Mathew J. Rodriguez, Carlos J. Sorlie, Paul D. Stein, Joel Towfighi, Amytis Turan, Tanya N. Virani, Salim S. Willey, Joshua Z. Woo, Daniel Yeh, Robert W. Turner, Melanie B. CA Amer Heart Assoc Stat Comm Stroke Stat Subcomm TI Heart Disease and Stroke Statistics-2015 Update A Report From the American Heart Association SO CIRCULATION LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; CHRONIC KIDNEY-DISEASE; BODY-MASS INDEX; NUTRITION-EXAMINATION-SURVEY; ACUTE MYOCARDIAL-INFARCTION; SUDDEN CARDIAC DEATH; CARDIOVASCULAR RISK-FACTORS; TYPE-2 DIABETES-MELLITUS; TRANSIENT ISCHEMIC ATTACK; ALL-CAUSE MORTALITY C1 [Mozaffarian, Dariush] Tufts Univ, Medford, MA 02155 USA. [Arnett, Donna K.; Howard, Virginia J.; Judd, Suzanne E.; Muntner, Paul] Univ Alabama Birmingham, Birmingham, AL USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Blaha, Michael J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Cushman, Mary] Univ Vermont, Burlington, VT 05405 USA. [de Ferranti, Sarah] Childrens Hosp Boston, Boston, MA USA. [Despres, Jean-Pierre] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada. [Fullerton, Heather J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Go, Alan S.] Kaiser Permanente, Oakland, CA USA. [Huffman, Mark D.] Northwestern Univ, Evanston, IL 60208 USA. [Kissela, Brett M.] Univ Cincinnati, Acad Hlth Ctr, Cincinnati, OH 45221 USA. [Lackland, Daniel T.; Turan, Tanya N.] Med Univ S Carolina, Charleston, SC USA. [Lichtman, Judith H.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Lisabeth, Lynda D.; Neumar, Robert W.] Univ Michigan, Ann Arbor, MI 48109 USA. [Liu, Simin] Brown Univ, Providence, RI 02912 USA. [Mackey, Rachel H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Matchar, David B.] Duke Univ, Durham, NC 27706 USA. [McGuire, Darren K.] Univ Texas Southwestern Med Ctr, Houston, TX USA. [Mohler, Emile R., III] Univ Penn, Philadelphia, PA 19104 USA. [Mussolino, Michael E.] NIH, Bethesda, MD USA. [Nasir, Khurram] Baptist Hlth Med Grp, Houston, TX USA. [Nichol, Graham] Univ Washington, Seattle, WA 98195 USA. [Palaniappan, Latha] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Pandey, Dilip K.] Univ Illinois, Chicago, IL USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Rodriguez, Carlos J.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Sorlie, Paul D.] NHLBI, Bethesda, MD USA. [Stein, Joel; Willey, Joshua Z.] Columbia Univ, New York, NY 10027 USA. [Towfighi, Amytis] Univ So Calif, Los Angeles, CA 90089 USA. [Turner, Melanie B.] Amer Heart Assoc, Houston, TX USA. [Virani, Salim S.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Innovat, Methodist DeBakey Heart & Vasc Ctr,Michael E DeBa, Houston, TX 77030 USA. [Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mozaffarian, D (reprint author), Tufts Univ, Medford, MA 02155 USA. OI Mackey, Rachel/0000-0001-6088-2664; Turan, Tanya/0000-0001-5399-8845; Huffman, Mark/0000-0001-7412-2519; Benjamin, Emelia/0000-0003-4076-2336; Virani, Salim/0000-0001-9541-6954; Kissela, Brett/0000-0002-9773-4013 FU NCATS NIH HHS [UL1 TR000077, UL1 TR001425]; NHLBI NIH HHS [R01 HL104199]; NINDS NIH HHS [K23 NS073104] NR 1605 TC 1928 Z9 1977 U1 80 U2 324 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 27 PY 2015 VL 131 IS 4 BP E29 EP E322 DI 10.1161/CIR.0000000000000152 PG 294 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AZ7YR UT WOS:000348432100002 PM 25520374 ER PT J AU Cong, J Fan, TP Yang, XQ Squires, JW Cheng, GM Zhang, LL Zhang, Z AF Cong, Juan Fan, Tingpan Yang, Xiaoqian Squires, Jared Wynn Cheng, Guomei Zhang, Linlin Zhang, Zhan TI Structural and functional changes in maternal left ventricle during pregnancy: a three-dimensional speckle-tracking echocardiography study SO CARDIOVASCULAR ULTRASOUND LA English DT Article DE Pregnancy; Remodeling; Myocardial deformation; Three-dimension; Speckle-tracking echocardiography ID GLOBAL AREA STRAIN; QUANTIFICATION; DEFORMATION; VOLUMES; DISEASE; MOTION; HEART AB Background: Pregnancy represents a physiological adaptation to the transient load changes of maternal heart. This study aimed to investigate maternal left ventricle (LV) performance during normal pregnancy by three-dimensional speckle-tracking echocardiography (3D STE) parameters considering LV loading and shape. Methods: Sequential two-dimensional echocardiography (2DE) and 3D STE were performed on 68 women during each pregnancy trimester and 6 to 9 weeks after delivery, while thirty age-matched, healthy, nonpregnant women served as controls. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS) and global radial strain (GRS) were measured. Results: Increased cardiac index and progressive eccentric hypertrophy was detected, which subsequently recovered postpartum. In late pregnancy, GLS, GCS, GAS and GRS significantly decreased (P < 0.05) accompanied by a slight reduction of LV ejection fraction (EF) (P < 0.05), and these values returned postpartum to baseline level. All 3D strain indices correlated well with gestation age (P < 0.01), while compared to other components, GAS exhibited the strongest association with 3D EF (r = 0.549) and sphericity index (r = 0.328), and was the only parameter that correlated well with LV mass index (r = 0.22). Conclusions: This study gives normal ranges of 3D STE indices in pregnancy. 3D STE demonstrated modified myocardial deformation and changes in maternal LV structure and function during the gestation period. C1 [Cong, Juan; Fan, Tingpan] Zhengzhou Univ, Affiliated Hosp 3, Dept Ultrason Diag, Zhengzhou 450052, Henan Province, Peoples R China. [Cong, Juan; Yang, Xiaoqian; Cheng, Guomei; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Zhengzhou 450052, Henan Province, Peoples R China. [Cong, Juan; Yang, Xiaoqian; Cheng, Guomei; Zhang, Linlin; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Henan Prov Engn Res Ctr Perinatal Med, Zhengzhou 450052, Henan Province, Peoples R China. [Cong, Juan; Yang, Xiaoqian; Cheng, Guomei; Zhang, Linlin; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Henan Translat Med Engn Lab Maternal & Childrens, Zhengzhou 450052, Henan Province, Peoples R China. [Squires, Jared Wynn] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Zhang, Z (reprint author), Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Zhengzhou 450052, Henan Province, Peoples R China. EM zhangzhanzdsfy@126.com FU Henan Provincial Healthy Talents of Scientific and Technological Innovative Program [ID_124200510005] FX This work was supported by the Henan Provincial Healthy Talents of Scientific and Technological Innovative Program (Grant ID_124200510005). NR 26 TC 7 Z9 7 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-7120 J9 CARDIOVASC ULTRASOUN JI Cardiovasc. Ultrasound PD JAN 27 PY 2015 VL 13 AR 6 DI 10.1186/1476-7120-13-6 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CC0XM UT WOS:000350063200002 PM 25626356 ER PT J AU Frakt, AB AF Frakt, Austin B. TI Hospital Consolidation Isn't the Key to Lowering Costs and Raising Quality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 [Frakt, Austin B.] Boston VA Healthcare Syst, Boston, MA USA. [Frakt, Austin B.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Frakt, Austin B.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Frakt, AB (reprint author), Boston VA Healthcare Syst, Boston, MA USA. EM afrakt@gmail.com NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 27 PY 2015 VL 313 IS 4 BP 345 EP 345 DI 10.1001/jama.2014.17412 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CA7BS UT WOS:000349072600003 PM 25626023 ER PT J AU Leroy, F Cai, Q Bogart, SL Dubois, J Coulon, O Monzalvo, K Fischer, C Glasel, H Van der Haegen, L Benezita, A Lin, CP Kennedy, DN Ihara, AS Hertz-Pannier, L Moutard, ML Poupon, C Brysbaert, M Roberts, N Hopkins, WD Mangin, JF Dehaene-Lambertz, G AF Leroy, Francois Cai, Qing Bogart, Stephanie L. Dubois, Jessica Coulon, Olivier Monzalvo, Karla Fischer, Clara Glasel, Herve Van der Haegen, Lise Benezita, Audrey Lin, Ching-Po Kennedy, David N. Ihara, Aya S. Hertz-Pannier, Lucie Moutard, Marie-Laure Poupon, Cyril Brysbaert, Marc Roberts, Neil Hopkins, William D. Mangin, Jean-Francois Dehaene-Lambertz, Ghislaine TI New human-specific brain landmark: The depth asymmetry of superior temporal sulcus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE brain; anatomy; asymmetry; human-specific; STS ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; PLANUM TEMPORALE; LANGUAGE LATERALIZATION; STRUCTURAL ASYMMETRIES; LEFT-HANDERS; AREA; HANDEDNESS; INFANTS; FMRI AB Identifying potentially unique features of the human cerebral cortex is a first step to understanding how evolution has shaped the brain in our species. By analyzing MR images obtained from 177 humans and 73 chimpanzees, we observed a human-specific asymmetry in the superior temporal sulcus at the heart of the communication regions and which we have named the "superior temporal asymmetrical pit" (STAP). This 45-mm-long segment ventral to Heschl's gyrus is deeper in the right hemisphere than in the left in 95% of typical human subjects, from infanthood till adulthood, and is present, irrespective of handedness, language lateralization, and sex although it is greater in males than in females. The STAP also is seen in several groups of atypical subjects including persons with situs inversus, autistic spectrum disorder, Turner syndrome, and corpus callosum agenesis. It is explained in part by the larger number of sulcal interruptions in the left than in the right hemisphere. Its early presence in the infants of this study as well as in fetuses and premature infants suggests a strong genetic influence. Because this asymmetry is barely visible in chimpanzees, we recommend the STAP region during midgestation as an important phenotype to investigate asymmetrical variations of gene expression among the primate lineage. This genetic target may provide important insights regarding the evolution of the crucial cognitive abilities sustained by this sulcus in our species, namely communication and social cognition. C1 [Leroy, Francois; Dubois, Jessica; Monzalvo, Karla; Glasel, Herve; Benezita, Audrey; Dehaene-Lambertz, Ghislaine] CEA, Off Atom Energy & Alternat Energies, INSERM, NeuroSpin,Cognit Neuroimaging Unit,U992, F-91191 Gif Sur Yvette, France. [Fischer, Clara; Brysbaert, Marc; Mangin, Jean-Francois] CEA, Off Atom Energy & Alternat Energies, INSERM, NeuroSpin,Anal & Proc Informat Unit, F-91191 Gif Sur Yvette, France. [Hertz-Pannier, Lucie] CEA, Off Atom Energy & Alternat Energies, INSERM, NeuroSpin,Clin & Translat Applicat Res Unit,U663, F-91191 Gif Sur Yvette, France. [Poupon, Cyril] CEA, Off Atom Energy & Alternat Energies, INSERM, NeuroSpin,Nucl Magnet Resonance Imaging & Spect U, F-91191 Gif Sur Yvette, France. [Cai, Qing] E China Normal Univ, Shanghai Key Lab Brain Funct Genom, Shanghai 200241, Peoples R China. [Bogart, Stephanie L.; Hopkins, William D.] Emory Univ, Yerkes Reg Primate Res Ctr, Div Dev & Cognit Neurosci, Atlanta, GA 30322 USA. [Coulon, Olivier] Aix Marseille Univ, UMR CNRS 7296, Lab Syst & Informat Sci, F-13284 Marseille, France. [Van der Haegen, Lise] Univ Ghent, Dept Expt Psychol, B-9000 Ghent, Belgium. [Lin, Ching-Po] Natl Yang Ming Univ, Inst Neurosci, Taipei 112, Taiwan. [Kennedy, David N.] Massachusetts Gen Hosp, Ctr Neurosci, Ctr Morphometr Anal, Boston, MA 02114 USA. [Ihara, Aya S.] Natl Inst Informat & Commun Technol, Ctr Informat & Neural Networks, Osaka 5650871, Japan. [Moutard, Marie-Laure] Trousseau Hosp, AP HP, Neuropediat Dept, F-75012 Paris, France. [Roberts, Neil] Univ Edinburgh, Coll Med & Vet Med, Clin Res Imaging Ctr, Edinburgh EH8 9YL, Midlothian, Scotland. RP Leroy, F (reprint author), CEA, Off Atom Energy & Alternat Energies, INSERM, NeuroSpin,Cognit Neuroimaging Unit,U992, F-91191 Gif Sur Yvette, France. EM francois.leroy@cea.fr RI Dubois, Jessica/P-2461-2014; OI Dubois, Jessica/0000-0003-4865-8111; Brysbaert, Marc/0000-0002-3645-3189 FU McDonnell Foundation; Bettencourt-Schueller Foundation FX We thank the ABIDE initiative, the Laboratory for Neurocognitive and Imaging Research (Kennedy Krieger Institute, Baltimore, MD), and Roberto Toro for the dataset related to normally developing and autistic children; specifically, from the Laboratory for Neurocognitive and Imaging Research, we thank Anita Barber, Rebecca Buhlman, Brian Caffo, Deana Crocetti, Suresh Joel, John Muschelli, Carrie Nettles, James Pekar, Kristie Sweeney, Michelle Talley, Mary Beth Nebel, and Stewart Mostofsky. We also thank Nicolas Molko and Stanislas Dehaene for the dataset related to Turner syndrome. Finally, we are grateful to the NeuroSpin teams for their help in the acquisition of infants and children data. This work was supported by the McDonnell and Bettencourt-Schueller Foundations. NR 49 TC 15 Z9 15 U1 4 U2 27 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 27 PY 2015 VL 112 IS 4 BP 1208 EP 1213 DI 10.1073/pnas.1412389112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ7SB UT WOS:000348417000064 PM 25583500 ER PT J AU Warren, HS Tompkins, RG Moldawer, LL Seok, J Xu, WH Mindrinos, MN Maier, RV Xiao, WZ Davis, RW AF Warren, H. Shaw Tompkins, Ronald G. Moldawer, Lyle L. Seok, Junhee Xu, Weihong Mindrinos, Michael N. Maier, Ronald V. Xiao, Wenzhong Davis, Ronald W. TI Mice are not men SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter C1 [Warren, H. Shaw; Tompkins, Ronald G.; Xiao, Wenzhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Warren, H. Shaw; Tompkins, Ronald G.; Xiao, Wenzhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Warren, H. Shaw; Tompkins, Ronald G.; Xiao, Wenzhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Moldawer, Lyle L.] Univ Florida, Dept Surg, Gainesville, FL 32608 USA. [Seok, Junhee] Korea Univ, Sch Elect Engn, Seoul 136713, South Korea. [Xu, Weihong; Mindrinos, Michael N.; Davis, Ronald W.] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94305 USA. [Maier, Ronald V.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98195 USA. RP Xiao, WZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. EM wenzhong.xiao@mgh.harvard.edu FU NIGMS NIH HHS [R01 GM104481, R24 GM102656, U54 GM062119] NR 2 TC 21 Z9 21 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 27 PY 2015 VL 112 IS 4 BP E345 EP E345 DI 10.1073/pnas.1414857111 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ7SB UT WOS:000348417000003 PM 25540422 ER PT J AU Mehta, AJ Kubzansky, LD Coull, BA Kloog, I Koutrakis, P Sparrow, D Spiro, A Vokonas, P Schwartz, J AF Mehta, Amar J. Kubzansky, Laura D. Coull, Brent A. Kloog, Itai Koutrakis, Petros Sparrow, David Spiro, Avron, III Vokonas, Pantel Schwartz, Joel TI Associations between air pollution and perceived stress: the Veterans Administration Normative Aging Study SO ENVIRONMENTAL HEALTH LA English DT Article DE Aged; Air pollution; Male; Particulate matter; Prospective studies; Stress; Psychological ID PARTICULATE MATTER; PSYCHOSOCIAL FACTORS; NOISE EXPOSURE; LUNG-FUNCTION; OLDER-ADULTS; RISK-FACTOR; HEALTH; DEPRESSION; MORTALITY; INFLAMMATION AB Background: There is mixed evidence suggesting that air pollution may be associated with increased risk of developing psychiatric disorders. We aimed to investigate the association between air pollution and non-specific perceived stress, often a precursor to development of affective psychiatric disorders. Methods: This longitudinal analysis consisted of 987 older men participating in at least one visit for the Veterans Administration Normative Aging Study between 1995 and 2007 (n = 2,244 visits). At each visit, participants were administered the 14-item Perceived Stress Scale (PSS), which quantifies stress experienced in the previous week. Scores ranged from 0-56 with higher scores indicating increased stress. Differences in PSS score per interquartile range increase in moving average (1, 2, and 4-weeks) of air pollution exposures were estimated using linear mixed-effects regression after adjustment for age, race, education, physical activity, anti-depressant medication use, seasonality, meteorology, and day of week. We also evaluated effect modification by season (April-September and March-October for warm and cold season, respectively). Results: Fine particles (PM2.5), black carbon (BC), nitrogen dioxide, and particle number counts (PNC) at moving averages of 1, 2, and 4-weeks were associated with higher perceived stress ratings. The strongest associations were observed for PNC; for example, a 15,997 counts/cm(3) interquartile range increase in 1-week average PNC was associated with a 3.2 point (95% CI: 2.1-4.3) increase in PSS score. Season modified the associations for specific pollutants; higher PSS scores in association with PM2.5, BC, and sulfate were observed mainly in colder months. Conclusions: Air pollution was associated with higher levels of perceived stress in this sample of older men, particularly in colder months for specific pollutants. C1 [Mehta, Amar J.; Koutrakis, Petros; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Kubzansky, Laura D.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA. [Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Kloog, Itai] Ben Gurion Univ Negev, Dept Geog & Environm Dev, IL-84105 Beer Sheva, Israel. [Sparrow, David; Spiro, Avron, III; Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Sparrow, David] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Vokonas, Pantel] Boston Univ, Sch Med, Dept Med, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Mehta, AJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr,West 415,401 Pk Dr, Boston, MA 02215 USA. EM amehta@hsph.harvard.edu FU National Institute of Environmental Health Sciences [ES014663-01A2, P01 ES09825]; U.S. Environmental Protection Agency [EPA R832416, R827353, R83241601]; Cooperative Studies Program/Epidemiology Research and Information Center of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts; NIH [R01-AG018436]; VA Research Career Scientist award; VA Senior Research Career Scientist award; USEPA [R827353, R83241601, R832416]; USEPA (EPA Clean Air Research Center grant) [RD83479801] FX The authors thank the participants and staff of the VA Normative Aging Study. This work was supported by the grants from the National Institute of Environmental Health Sciences (ES014663-01A2 and P01 ES09825) and from the U.S. Environmental Protection Agency (EPA R832416, R827353, and R83241601). The Veterans Affairs (VA) Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts. Support was also provided by NIH grant R01-AG018436. This research was also supported by a VA Research Career Scientist award to David Sparrow and a VA Senior Research Career Scientist award to Avron Spiro, III.; This publication was made possible by USEPA grant (R832416, R827353, R83241601, and EPA Clean Air Research Center grant RD83479801). Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the USEPA. Further, USEPA does not endorse the purchase of any commercial products or services mentioned in the publication. NR 65 TC 3 Z9 3 U1 6 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD JAN 27 PY 2015 VL 14 AR UNSP 10 DI 10.1186/1476-069X-14-10 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA CA6RM UT WOS:000349043200001 PM 25627872 ER PT J AU Singer, DE Ezekowitz, MD AF Singer, Daniel E. Ezekowitz, Michael D. TI Adding Rigor to Stroke Risk Prediction in Atrial Fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE anticoagulation; atrial fibrillation; risk scores; stroke prevention ID STRATIFICATION; GUIDELINES; MANAGEMENT; SCHEMES; ESC 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. [Ezekowitz, Michael D.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. RP Singer, DE (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. EM dsinger@partners.org NR 13 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 27 PY 2015 VL 65 IS 3 BP 233 EP 235 DI 10.1016/j.jacc.2014.11.013 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ2EA UT WOS:000348046200002 PM 25614419 ER PT J AU Ho, PM O'Donnell, CI Bradley, SM Grunwald, GK Helfrich, C Chapko, M Liu, CF Maddox, TM Tsai, TT Jesse, RL Fihn, SD Rumsfeld, JS AF Ho, P. Michael O'Donnell, Colin I. Bradley, Steven M. Grunwald, Gary K. Helfrich, Christian Chapko, Michael Liu, Chuan-Fen Maddox, Thomas M. Tsai, Thomas T. Jesse, Robert L. Fihn, Stephan D. Rumsfeld, John S. TI 1-Year Risk-Adjusted Mortality and Costs of Percutaneous Coronary Intervention in the Veterans Health Administration Insights From the VA CART Program SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE costs; health care delivery; ischemic heart disease; PCI; outcomes; value ID CARDIOVASCULAR DATA REGISTRY; ACUTE MYOCARDIAL-INFARCTION; REPEAT REVASCULARIZATION; QUALITY; PCI; PREDICTION; EFFICIENCY; OUTCOMES; DISEASE; SURGERY AB BACKGROUND There is significant interest in measuring health care value, but this concept has not been operationalized in specific patient cohorts. The longitudinal outcomes and costs for patients after percutaneous coronary intervention (PCI) provide an opportunity to measure an aspect of health care value. OBJECTIVES This study evaluated variations in 1-year outcomes (risk-adjusted mortality) and risk-standardized costs of care for all patients undergoing PCI in the Veterans Affairs (VA) system from 2007 to 2010. METHODS This retrospective cohort study evaluated all veterans undergoing PCI at any of 60 hospitals in the VA health care system, using data from the national VA Clinical Assessment, Reporting, and Tracking (CART) program. Primary outcomes were 1-year mortality and costs following PCI. Risk-standardized mortality and cost ratios were calculated, adjusting for cardiac and noncardiac comorbidities. RESULTS A median of 261 PCIs were performed in the 60 hospitals during the study period. Median 1-year unadjusted hospital mortality rate was 6.13%. Four hospitals were significantly above the 1-year risk-standardized median mortality rate, with median mortality ratios ranging from 1.23 to 1.28. No hospitals were significantly below median mortality. Median 1-year total unadjusted hospital costs were $46,302 per patient. There were 16 hospitals above and 19 hospitals below the risk-standardized median cost, with risk-standardized ratios ranging from 0.45 to 2.09, reflecting a much larger magnitude of variability in costs than in mortality. CONCLUSIONS There is much smaller variation in 1-year risk adjusted mortality than in risk-standardized costs after PCI in the VA. These findings suggest that there are opportunities to improve PCI value by reducing costs without compromising outcomes. This approach to evaluating outcomes and costs together may be a model for other health systems and accountable care organizations interested in operationalizing value measurement. (C) 2015 by the American College of Cardiology Foundation. C1 [Ho, P. Michael; O'Donnell, Colin I.; Bradley, Steven M.; Grunwald, Gary K.; Maddox, Thomas M.; Tsai, Thomas T.; Rumsfeld, John S.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. [Ho, P. Michael; O'Donnell, Colin I.; Bradley, Steven M.; Grunwald, Gary K.; Maddox, Thomas M.; Tsai, Thomas T.; Rumsfeld, John S.] Univ Colorado, Div Cardiol, Denver, CO 80220 USA. [Helfrich, Christian; Chapko, Michael; Liu, Chuan-Fen; Fihn, Stephan D.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Jesse, Robert L.] Dept Vet Affairs, Vet Hlth Adm, Washington, DC USA. [Fihn, Stephan D.] Vet Affairs Off Analyt & Business Intelligence, Washington, DC USA. RP Ho, PM (reprint author), Univ Colorado, Sect Cardiol, Denver Vet Affairs Med Ctr, 1055 Clermont St 111B, Denver, CO 80220 USA. EM michael.ho@va.gov RI Helfrich, Christian/D-2382-2016 OI Helfrich, Christian/0000-0002-9827-4768 FU Career Development Awards from VA Health Services Research and Development FX Drs. Bradley and Maddox are supported by Career Development Awards from VA Health Services Research and Development. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 19 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 27 PY 2015 VL 65 IS 3 BP 236 EP 242 DI 10.1016/j.jacc.2014.10.048 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ2EA UT WOS:000348046200003 PM 25614420 ER PT J AU Samarendra, P Mangione, MP AF Samarendra, Padmaraj Mangione, Michael P. TI Aortic Stenosis and Perioperative Risk With Noncardiac Surgery SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE clinical outcomes; heart failure; hypotension; intraoperative monitoring; phenylephrine ID CORONARY-ARTERY-DISEASE; LOW MORTALITY-RATES; VALVE-REPLACEMENT; CARDIAC RISK; SURGICAL-PROCEDURES; PERFORM WELL; COMPLICATIONS; OUTCOMES; HEMODYNAMICS; HOSPITALS AB Aortic stenosis (AS) is characterized as a high-risk index for cardiac complications during noncardiac surgery. The American College of Cardiology/American Heart Association guidelines define severe AS as aortic valve area <= 1 cm(2), mean gradient of >= 40 mm Hg, and peak velocity of >= 4 m/s. As per current clinical practice, any of these characteristic features label a patient as at high risk for noncardiac surgery. However, these parameters appear inconsistent, particularly with respect to the aortic valve area cutoff value. The perioperative risk associated with AS during noncardiac surgery depends upon its severity (moderate vs. severe), clinical status, and the complexity of the surgical procedure (low to intermediate risk vs. high risk). A critical analysis of old and new data from published studies indicates that the significance of the presence of AS in patients undergoing noncardiac surgery is overemphasized in studies that predate the more recent advances in echocardiography and cardiac catheterization in assessment of aortic stenosis, anesthetic and surgical techniques, as well as post-operative patient care. (C) 2015 by the American College of Cardiology Foundation. C1 [Samarendra, Padmaraj] VA Med Ctr, Noninvas Cardiol & Echocardiog Lab, Pittsburgh, PA 15240 USA. [Samarendra, Padmaraj] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Mangione, Michael P.] VA Pittsburgh Hlth Care Syst, Dept Anesthesia, Pittsburgh, PA USA. [Mangione, Michael P.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. RP Samarendra, P (reprint author), VA Med Ctr, Univ Dr C, Pittsburgh, PA 15240 USA. EM Padmaraj@aol.com NR 40 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 27 PY 2015 VL 65 IS 3 BP 295 EP 302 DI 10.1016/j.jacc.2014.10.051 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ2EA UT WOS:000348046200012 PM 25614427 ER PT J AU Boatin, AA Wylie, B Goldfarb, I Azevedo, R Pittel, E Ng, C Haberer, J AF Boatin, Adeline A. Wylie, Blair Goldfarb, Ilona Azevedo, Robin Pittel, Elena Ng, Courtney Haberer, Jessica TI Wireless Fetal Heart Rate Monitoring in Inpatient Full-Term Pregnant Women: Testing Functionality and Acceptability SO PLoS One LA English DT Article AB We tested functionality and acceptability of a wireless fetal monitoring prototype technology in pregnant women in an inpatient labor unit in the United States. Women with full-term singleton pregnancies and no evidence of active labor were asked to wear the prototype technology for 30 minutes. We assessed functionality by evaluating the ability to successfully monitor the fetal heartbeat for 30 minutes, transmit this data to Cloud storage and view the data on a web portal. Three obstetricians also rated fetal cardiotocographs on ease of readability. We assessed acceptability by administering closed and open-ended questions on perceived utility and likeability to pregnant women and clinicians interacting with the prototype technology. Thirty-two women were enrolled, 28 of whom (87.5%) successfully completed 30 minutes of fetal monitoring including transmission of cardiotocographs to the web portal. Four sessions though completed, were not successfully uploaded to the Cloud storage. Six non-study clinicians interacted with the prototype technology. The primary technical problem observed was a delay in data transmission between the prototype and the web portal, which ranged from 2 to 209 minutes. Delays were ascribed to Wi-Fi connectivity problems. Recorded cardiotocographs received a mean score of 4.2/5 (+/- 1.0) on ease of readability with an interclass correlation of 0.81(95% CI 0.45, 0.96). Both pregnant women and clinicians found the prototype technology likable (81.3% and 66.7% respectively), useful (96.9% and 66.7% respectively), and would either use it again or recommend its use to another pregnant woman (77.4% and 66.7% respectively). In this pilot study we found that this wireless fetal monitoring prototype technology has potential for use in a United States inpatient setting but would benefit from some technology changes. We found it to be acceptable to both pregnant women and clinicians. Further research is needed to assess feasibility of using this technology in busy inpatient settings. C1 [Boatin, Adeline A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02163 USA. [Wylie, Blair; Goldfarb, Ilona] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Maternal Fetal Med,Dept Obstet & Gynecol, Boston, MA USA. [Azevedo, Robin; Pittel, Elena] Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. [Ng, Courtney; Haberer, Jessica] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth, Boston, MA USA. RP Boatin, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02163 USA. EM aboatin@partners.org FU Gary and Mary West Health Institute FX This study was conducted at the Massachusetts General Hospital with support provided by the Gary and Mary West Health Institute, an independent, not for profit medical research organization that works with healthcare providers and research institutions to create new, more effective ways of delivering care. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 9 TC 2 Z9 2 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 26 PY 2015 VL 10 IS 1 AR e0117043 DI 10.1371/journal.pone.0117043 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ8MR UT WOS:000348470400016 PM 25622043 ER PT J AU Swerdlow, DI Preiss, D Kuchenbaecker, KB Holmes, MV Engmann, JEL Shah, T Sofat, R Stender, S Johnson, PCD Scott, RA Leusink, M Verweij, N Sharp, SJ Guo, YR Giambartolomei, C Chung, C Peasey, A Amuzu, A Li, K Palmen, J Howard, P Cooper, JA Drenos, F Li, YR Lowe, G Gallacher, J Stewart, MCW Tzoulaki, I Buxbaum, SG Daphne, LV Forouhi, NG Onland-Moret, NC van der Schouw, YT Schnabel, RB Hubacek, JA Kubinova, R Baceviciene, M Tamosiunas, A Pajak, A Topor-Madry, R Stepaniak, U Malyutina, SA Baldassarre, D Sennblad, B Tremoli, E de Faire, U Veglia, F Ford, I Jukema, JW Westendorp, RGJ de Borst, GJ de Jong, PA Algra, A Spiering, W Maitland-van der Zee, AH Klungel, OH de Boer, A Doevendans, PA Eaton, CB Robinson, JG Duggan, D Kjekshus, J Downs, JR Gotto, AM Keech, AC Marchioli, R Tognoni, G Sever, PS Poulter, NR Waters, DD Pedersen, TR Amarenco, P Nakamura, H McMurray, JJV Lewsey, JD Chasman, DI Ridker, PM Maggioni, AP Tavazzi, L Ray, KK Seshasai, SRK Manson, JE Price, JF Whincup, PH Morris, RW Lawlor, DA Smith, GD Ben-Shlomo, Y Schreiner, PJ Fornage, M Siscovick, DS Cushman, M Kumari, M Wareham, NJ Verschuren, WMM Redline, S Patel, SR Whittaker, JC Hamsten, A Delaney, JA Dale, C Gaunt, TR Wong, A Kuh, D Hardy, R Kathiresan, S Castillo, BA van der Harst, P Brunner, EJ Tybjaerg-Hansen, A Marmot, MG Krauss, RM Tsai, M Coresh, J Hoogeveen, RC Psaty, BM Lange, LA Hakonarson, H Dudbridge, F Humphries, SE Talmud, PJ Kivimaki, M Timpson, NJ Langenberg, C Asselbergs, FW Voevoda, M Bobak, M Pikhart, H Wilson, JG Reiner, AP Keating, BJ Hingorani, AD Sattar, N AF Swerdlow, Daniel I. Preiss, David Kuchenbaecker, Karoline B. Holmes, Michael V. Engmann, Jorgen E. L. Shah, Tina Sofat, Reecha Stender, Stefan Johnson, Paul C. D. Scott, Robert A. Leusink, Maarten Verweij, Niek Sharp, Stephen J. Guo, Yiran Giambartolomei, Claudia Chung, Christina Peasey, Anne Amuzu, Antoinette Li, Kawah Palmen, Jutta Howard, Philip Cooper, Jackie A. Drenos, Fotios Li, Yun R. Lowe, Gordon Gallacher, John Stewart, Marlene C. W. Tzoulaki, Ioanna Buxbaum, Sarah G. Daphne, L. van der A. Forouhi, Nita G. Onland-Moret, N. Charlotte van der Schouw, Yvonne T. Schnabel, Renate B. Hubacek, Jaroslav A. Kubinova, Ruzena Baceviciene, Migle Tamosiunas, Abdonas Pajak, Andrzej Topor-Madry, Roman Stepaniak, Urszula Malyutina, Sofi A. Baldassarre, Damiano Sennblad, Bengt Tremoli, Elena de Faire, Ulf Veglia, Fabrizio Ford, Ian Jukema, J. Wouter Westendorp, Rudi G. J. de Borst, Gert Jan de Jong, Pim A. Algra, Ale Spiering, Wilko Maitland-van der Zee, Anke H. Klungel, Olaf H. de Boer, Anthonius Doevendans, Pieter A. Eaton, Charles B. Robinson, Jennifer G. Duggan, David Kjekshus, John Downs, John R. Gotto, Antonio M. Keech, Anthony C. Marchioli, Roberto Tognoni, Gianni Sever, Peter S. Poulter, Neil R. Waters, David D. Pedersen, Terje R. Amarenco, Pierre Nakamura, Haruo McMurray, John J. V. Lewsey, James D. Chasman, Daniel I. Ridker, Paul M. Maggioni, Aldo P. Tavazzi, Luigi Ray, Kausik K. Seshasai, Sreenivasa Rao Kondapally Manson, Joann E. Price, Jackie F. Whincup, Peter H. Morris, Richard W. Lawlor, Debbie A. Smith, George Davey Ben-Shlomo, Yoav Schreiner, Pamela J. Fornage, Myriam Siscovick, David S. Cushman, Mary Kumari, Meena Wareham, Nick J. Verschuren, W. M. Monique Redline, Susan Patel, Sanjay R. Whittaker, John C. Hamsten, Anders Delaney, Joseph A. Dale, Caroline Gaunt, Tom R. Wong, Andrew Kuh, Diana Hardy, Rebecca Kathiresan, Sekar Castillo, Berta A. van der Harst, Pim Brunner, Eric J. Tybjaerg-Hansen, Anne Marmot, Michael G. Krauss, Ronald M. Tsai, Michael Coresh, Josef Hoogeveen, Ronald C. Psaty, Bruce M. Lange, Leslie A. Hakonarson, Hakon Dudbridge, Frank Humphries, Steve E. Talmud, Philippa J. Kivimaeki, Mika Timpson, Nicholas J. Langenberg, Claudia Asselbergs, Folkert W. Voevoda, Mikhail Bobak, Martin Pikhart, Hynek Wilson, James G. Reiner, Alex P. Keating, Brendan J. Hingorani, Aroon D. Sattar, Naveed CA DIAGRAM Consortium MAGIC Consortium InterAct Consortium TI HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials SO LANCET LA English DT Article ID HIGH-DOSE ATORVASTATIN; BODY-MASS INDEX; STATIN THERAPY; MENDELIAN RANDOMIZATION; ASSOCIATION ANALYSES; LDL CHOLESTEROL; METAANALYSIS; RISK; PREVENTION; DISEASE AB Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. Findings Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0.06 mmol/L (95% CI 0.05-0.07) lower LDL cholesterol and higher body weight (0.30 kg, 0.18-0.43), waist circumference (0.32 cm, 0.16-0.47), plasma insulin concentration (1.62%, 0.53-2.72), and plasma glucose concentration (0.23%, 0.02-0.44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1.02, 95% CI 1.00-1.05); the rs12916-T allele association was consistent (1.06, 1.03-1.09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0.92 mmol/L (95% CI 0.18-1.67) at 1-year of follow-up, increased bodyweight by 0.24 kg (95% CI 0.10-0.38 in all trials; 0.33 kg, 95% CI 0.24-0.42 in placebo or standard care controlled trials and 0.15 kg, 95% CI 0.39 to 0.08 in intensive-dose vs moderate-dose trials) at a mean of 4. 2 years (range 1.9-6.7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1.12, 95% CI 1.06-1.18 in all trials; 1.11, 95% CI 1.03-1. 20 in placebo or standard care controlled trials and 1.12, 95% CI 1.04-1. 22 in intensive-dose vs moderate dose trials). Interpretation The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. C1 [Swerdlow, Daniel I.; Holmes, Michael V.; Engmann, Jorgen E. L.; Shah, Tina; Asselbergs, Folkert W.; Hingorani, Aroon D.] UCL, UCL Inst Cardiovasc Sci & Farr Inst, London, England. [Sofat, Reecha] UCL, UCL Dept Med, London, England. [Chung, Christina; Peasey, Anne; Kumari, Meena; Brunner, Eric J.; Marmot, Michael G.; Kivimaeki, Mika; Bobak, Martin; Pikhart, Hynek] UCL, UCL Res Dept Epidemiol & Publ Hlth, London, England. [Giambartolomei, Claudia] UCL, UCL Genet Inst, London, England. [Morris, Richard W.] UCL, UCL Dept Primary Care & Populat Hlth, London, England. [Li, Kawah; Palmen, Jutta; Howard, Philip; Cooper, Jackie A.; Drenos, Fotios; Humphries, Steve E.; Talmud, Philippa J.] UCL, Ctr Cardiovasc Genet, London, England. [Wong, Andrew; Kuh, Diana; Hardy, Rebecca] UCL, MRCUnit Lifelong Hlth & Ageing, Inst Epidemiol & Hlth Care, London, England. [Preiss, David; McMurray, John J. V.; Sattar, Naveed] Univ Glasgow, BHF Glasgow Cardiovascular Res Ctr, Glasgow G12 8TA, Lanark, Scotland. [Johnson, Paul C. D.; Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Lowe, Gordon] Univ Glasgow, Inst Cardiovasc & Med, Glasgow, Lanark, Scotland. 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[Amarenco, Pierre] Denis Diderot Univ, Paris, France. [Nakamura, Haruo] Mitsukoshi Hlth & Welf Fdn, Tokyo, Japan. [Chasman, Daniel I.; Ridker, Paul M.; Manson, Joann E.] Harvard Univ, Div Prevent Med, Sch Med, Boston, MA USA. [Patel, Sanjay R.] Harvard Univ, Div Sleep Med, Sch Med, Boston, MA USA. [Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Tavazzi, Luigi] Maria Cecilia Hosp, GVM Care & Res, ES Hlth Sci Fdn, Cotignola, RA, Italy. [Ray, Kausik K.; Seshasai, Sreenivasa Rao Kondapally] Cardiac & Cell Sci Res Inst, London, England. [Whincup, Peter H.] St Georges Univ, London, England. [Lawlor, Debbie A.; Smith, George Davey; Gaunt, Tom R.; Timpson, Nicholas J.] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England. [Lawlor, Debbie A.; Smith, George Davey; Ben-Shlomo, Yoav; Timpson, Nicholas J.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Tsai, Michael] Univ Minnesota, Minneapolis, MN USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Med, Dept Epidemiol, Cardiovascular Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Delaney, Joseph A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Cushman, Mary] Univ Vermont, Dept Med, Colchester, VT USA. [Cushman, Mary] Univ Vermont, Dept Pathol, Colchester, VT USA. [Whittaker, John C.] GlaxoSmithKline, Stevenage, Herts, England. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Broad Inst, Program Med & Populat Gent, Cambridge, MA USA. [Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Hoogeveen, Ronald C.] Baylor Coll Med, Dept Med, Div Atherosclerosis & Vasc Med, Houston, TX 77030 USA. [Lange, Leslie A.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. [Asselbergs, Folkert W.] Durrer Ctr Cardiogenet Res, ICIN Netherlands Heart Inst, Utrecht, Netherlands. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Preiss, D (reprint author), Univ Glasgow, BHF Glasgow Cardiovascular Res Ctr, Glasgow G12 8TA, Lanark, Scotland. EM d.swerdlow@ucl.ac.uk; david.preiss@glasgow.ac.uk RI Gaunt, Tom/O-3918-2014; Guo, Yiran/H-4120-2011; de Jong, Pim/G-7220-2014; Onland-Moret, N. Charlotte/G-9185-2011; Fox, Laura /C-6249-2016; Klungel, Olaf/I-9563-2016; Verweij, Niek/A-4499-2017; Davey Smith, George/A-7407-2013; Baldassarre, Damiano/J-3295-2016; OI Maggioni, Aldo Pietro/0000-0003-2764-6779; mcmurray, john/0000-0002-6317-3975; Lawlor, Debbie A/0000-0002-6793-2262; Morris, Richard/0000-0001-7240-4563; Pikhart, Hynek/0000-0001-5277-4049; TREMOLI, ELENA/0000-0002-0929-6106; Whincup, Peter/0000-0002-5589-4107; Johnson, Paul/0000-0001-6663-7520; Humphries, Stephen E/0000-0002-8221-6547; Patel, Sanjay/0000-0002-9142-5172; Kumari, Meena/0000-0001-9716-1035; Verweij, Niek/0000-0002-4303-7685; Forouhi, Nita/0000-0002-5041-248X; Timpson, Nicholas/0000-0002-7141-9189; Marmot, Michael/0000-0002-2431-6419; Gaunt, Tom/0000-0003-0924-3247; Guo, Yiran/0000-0002-6549-8589; de Jong, Pim/0000-0003-4840-6854; Davey Smith, George/0000-0002-1407-8314; Baldassarre, Damiano/0000-0002-2766-8882; Talmud, Philippa/0000-0002-5560-1933; Swerdlow, Daniel/0000-0002-7946-3459; Preiss, David/0000-0003-3139-1836 FU Medical Research Council (MRC) Doctoral Training Award; Rosetrees Trust; MRC Population Health Scientist Fellowship [G0802432]; National Institutes of Health (NIH); British Heart Foundation (Schillingford) Clinical Training Fellowship [FS/07/011]; Danish MRC [10-083788]; Research Fund at Rigshospitalet; Copenhagen University Hospital; Chief Physician Johan Boserup and Lise Boserup's Fund; Wellcome Trust [064947/Z/01/Z, 081081/Z/06/Z]; National Institute on Aging [1R01 AG23522-01]; MacArthur Foundation; National Institute on Minority Health; Health Disparities of the NIH [P20MD006899]; MRC; Ministry of Health, Czech Republic [00023001]; Magnus Bergvall Foundation; Foundation for Old Servants; National Institute for Healthy Ageing [05060810]; British Heart Foundation; Chest, Heart and Stroke Scotland; Wellcome Trust; British Heart Foundation [RG/13/2/30098]; MooDFOOD Collaborative Project (FP7) [613598]; NIH [NIH U19 HL065797, NHLBI 33014]; British Heart Foundation (BHF) [RG 08/008, PG/07/133/24260]; EMIF [115372] FX DIS is supported by a Medical Research Council (MRC) Doctoral Training Award and a grant from the Rosetrees Trust. MVH is supported by a MRC Population Health Scientist Fellowship (G0802432). JELL is supported by grants from the National Institutes of Health (NIH) and the MRC. RS has been supported by a British Heart Foundation (Schillingford) Clinical Training Fellowship (FS/07/011). SS is supported by the Danish MRC (grant no. 10-083788), the Research Fund at Rigshospitalet, Copenhagen University Hospital, and Chief Physician Johan Boserup and Lise Boserup's Fund. CC and APe are supported by grants from the Wellcome Trust (064947/Z/01/Z and 081081/Z/06/Z), a grant from the National Institute on Aging (1R01 AG23522-01), and a grant from MacArthur Foundation. SGB was supported by an award from the National Institute on Minority Health and Health Disparities of the NIH (award number P20MD006899). NGF is supported by a grant from the MRC. JAH is supported by the project (Ministry of Health, Czech Republic) for the development of research organisation 00023001 (IKEM, Prague, Czech Republic). APa is supported by grants from the Wellcome Trust (064947/Z/01/Z and 081081/Z/06/Z) and National Institute on Aging (1R01 AG23522-01). BS is supported by the Magnus Bergvall Foundation and the Foundation for Old Servants. RGJW is supported by the National Institute for Healthy Ageing (Grant 05060810). JFP is supported by the British Heart Foundation; Chest, Heart and Stroke Scotland; the Wellcome Trust; and the MRC. DAL, GDS, and NJT work in a unit that receives funding from the MRC and University of Bristol. EJB's research is supported by a British Heart Foundation programme grant (RG/13/2/30098) and the MooDFOOD Collaborative Project (FP7 grant 613598). RMK is supported by the NIH (grant NIH U19 HL065797). SEH and PJT are supported by the British Heart Foundation (BHF RG 08/008, PG/07/133/24260), MRC, and NIH (grant NHLBI 33014). MKi is supported by the National Institute on Aging (AG034454); the M RC (K013351); the National Heart, Lung and Blood Institute (HL036310); and the Academy of Finland. NJT is supported by the MRC (grant G0600705). FWA is supported by a clinical fellowship from the Netherlands Organisation for Health Research and Development (ZonMw grant 90700342). ADH is supported by University College London NIHR Biomedical Research Centre. NS's research is supported by the British Heart Foundation, Diabetes UK, and the EU/EF PIA Innovative Medicines Initiative Joint Undertaking (EMIF grant 115372). We thank Merck and Novartis for contributing data to the statin trials analysis. Details of grants or other support for included studies are provided in the appendix. NR 40 TC 123 Z9 126 U1 11 U2 51 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JAN 24 PY 2015 VL 385 IS 9965 BP 351 EP 361 DI 10.1016/S0140-6736(14)61183-1 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AZ9CN UT WOS:000348509000028 PM 25262344 ER PT J AU Ursea, R De Castro, D Bowen, TJ Chan, CC AF Ursea, Roxana De Castro, Dawn Bowen, Trent J. Chan, Chi-Chao TI The role of conjunctival biopsy in the diagnosis of granulomatosis with polyangiitis SO JOURNAL OF OPHTHALMIC INFLAMMATION AND INFECTION LA English DT Article DE Conjunctivitis; Cornea; Ulceration; Biopsy; Granulomatosis with polyangiitis ID WEGENERS-GRANULOMATOSIS; PRESENTING FEATURE; LIMITED FORMS; MANIFESTATIONS AB Background: The purpose of this study is to describe a patient who was diagnosed with granulomatosis with polyangiitis based on conjunctival biopsy. This study is a case report and review of the literature. Findings: A 48-year-old Caucasian woman presented with a 2-week history of a left eye peripheral corneal ulcer with adjacent conjunctivitis and a 4-month history of a non-resolving productive cough. Given her elevated serum perinuclear antineutrophil cytoplasmic antibody (P-ANCA) and erythrocyte sedimentation rate (ESR) levels as well as a chest computed topography (CT) that showed bilateral patchy infiltrates, suspicion of limited granulomatosis with polyangiitis with lung and ocular involvement was high. Because bronchoalveolar lavage was nondiagnostic for granulomatous disease, conjunctival biopsy was initially attempted in order to avoid a more invasive lung biopsy. The conjunctival biopsy revealed mixed subacute inflammatory mediators and vasculitis consistent with granulomatosis with polyangiitis. Conclusions: Conjunctival biopsy may be a valuable, minimally invasive method for diagnosing systemic granulomatosis with polyangiitis. C1 [Ursea, Roxana] Univ Arizona, Dept Ophthalmol & Vis Sci, Coll Med, Tucson, AZ 85711 USA. [De Castro, Dawn] Massachusetts Eye & Ear Infirm, Oculoplast Serv, Boston, MA 02114 USA. [Bowen, Trent J.] Univ Arizona, Coll Med, Tucson, AZ 85711 USA. [Chan, Chi-Chao] NEI, Immunopathol Sect, Bethesda, MD 20892 USA. RP Ursea, R (reprint author), Univ Arizona, Dept Ophthalmol & Vis Sci, Coll Med, Tucson, AZ 85711 USA. EM roxanaursea@hotmail.com NR 26 TC 2 Z9 2 U1 0 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1869-5760 J9 J OPHTHALMIC INFLAMM JI J. Ophthalmic Inflamm. Infect. PD JAN 23 PY 2015 VL 5 AR 1 DI 10.1186/s12348-014-0033-9 PG 5 WC Ophthalmology SC Ophthalmology GA CZ2JP UT WOS:000366931600001 PM 25632308 ER PT J AU Hori, Y Takeda, S Cho, H Wegmann, S Shoup, TM Takahashi, K Irimia, D Elmaleh, DR Hyman, BT Hudry, E AF Hori, Yukiko Takeda, Shuko Cho, Hansang Wegmann, Susanne Shoup, Timothy M. Takahashi, Kazue Irimia, Daniel Elmaleh, David R. Hyman, Bradley T. Hudry, Eloise TI A Food and Drug Administration-approved Asthma Therapeutic Agent Impacts Amyloid beta in the Brain in a Transgenic Model of Alzheimer Disease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG-TERM POTENTIATION; FIBRIL FORMATION; PRECURSOR PROTEIN; IN-VIVO; MUTANT PRESENILIN-1; SYNAPTIC PLASTICITY; SECRETED OLIGOMERS; COGNITIVE FUNCTION; FLAVONOID FISETIN; OXIDATIVE STRESS AB Interfering with the assembly of Amyloid beta (A beta) peptides from monomer to oligomeric species and fibrils or promoting their clearance from the brain are targets of anti-A beta-directed therapies in Alzheimer disease. Here we demonstrate that cromolyn sodium (disodium cromoglycate), a Food and Drug Administration-approved drug already in use for the treatment of asthma, efficiently inhibits the aggregation of A beta monomers into higher-order oligomers and fibrils in vitro without affecting A beta production. In vivo, the levels of soluble A beta are decreased by over 50% after only 1 week of daily intraperitoneally administered cromolyn sodium. Additional in vivo microdialysis studies also show that this compound decreases the half-life of soluble A beta in the brain. These data suggest a clear effect of a peripherally administered, Food and Drug Administration-approved medication on A beta economy, supporting further investigation of the potential long-term efficacy of cromolyn sodium in Alzheimer disease. C1 [Hori, Yukiko; Takeda, Shuko; Wegmann, Susanne; Hyman, Bradley T.; Hudry, Eloise] Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. [Cho, Hansang; Irimia, Daniel] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02129 USA. [Shoup, Timothy M.; Elmaleh, David R.] Harvard Univ, Med Sch Charlestown, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02129 USA. [Takahashi, Kazue] Harvard Univ, Med Sch Charlestown, Serv Pediat, Boston, MA 02129 USA. RP Hudry, E (reprint author), MA Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Alzheimers Dis Res Lab, Bldg 114,16th St, Charlestown, MA 02129 USA. EM ehudry@partners.org FU AZ Therapies Inc.; Uehara Memorial Foundation; Japan Society for the Promotion of Science; Dreyfoos Fund Against Alzheimer's Disease FX This study was supported by AZ Therapies Inc., by a postdoctoral fellowship from the Uehara Memorial Foundation (to Y. H.), by the Postdoctoral Fellowship for Research Abroad from the Japan Society for the Promotion of Science (to S. T.), and by the Dreyfoos Fund Against Alzheimer's Disease. NR 50 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 23 PY 2015 VL 290 IS 4 BP 1966 EP 1978 DI 10.1074/jbc.M114.586602 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CA0EH UT WOS:000348588000006 PM 25468905 ER PT J AU Sea, K Sohn, SH Durazo, A Sheng, YW Shaw, BF Cao, XH Taylor, AB Whitson, LJ Holloway, SP Hart, PJ Cabelli, DE Gralla, EB Valentine, JS AF Sea, Kevin Sohn, Se Hui Durazo, Armando Sheng, Yuewei Shaw, Bryan F. Cao, Xiaohang Taylor, Alexander B. Whitson, Lisa J. Holloway, Stephen P. Hart, P. John Cabelli, Diane E. Gralla, Edith Butler Valentine, Joan Selverstone TI Insights into the Role of the Unusual Disulfide Bond in Copper-Zinc Superoxide Dismutase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU,ZN-SUPEROXIDE DISMUTASE; SACCHAROMYCES-CEREVISIAE; ATOMIC-RESOLUTION; PULSE-RADIOLYSIS; REDUCED FORM; METAL; AGGREGATION; YEAST; ALS AB The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human SOD1 (hSOD) and yeast SOD1 lacking the disulfide bond. We determined x-ray crystal structures of metal-bound and metal-deficient hC57S SOD1. C57S hSOD1 isolated from yeast contained four zinc ions per protein dimer and was structurally very similar to wild type. The addition of copper to this four-zinc protein gave properly reconstituted 2Cu, 2Zn C57S hSOD, and its spectroscopic properties indicated that the coordination geometry of the copper was remarkably similar to that of holo wild type hSOD1. In contrast, the addition of copper and zinc ions to apo C57S human SOD1 failed to give proper reconstitution. Using pulse radiolysis, we determined SOD activities of yeast and human SOD1s lacking disulfide bonds and found that they were enzymatically active at similar to 10% of the wild type rate. These results are contrary to earlier reports that the intrasubunit disulfide bonds in SOD1 are essential for SOD activity. Kinetic studies revealed further that the yeast mutant SOD1 had less ionic attraction for superoxide, possibly explaining the lower rates. Saccharomyces cerevisiae cells lacking the sod1 gene do not grow aerobically in the absence of lysine, but expression of C57S SOD1 increased growth to 30-50% of the growth of cells expressing wild type SOD1, supporting that C57S SOD1 retained a significant amount of activity. C1 [Sea, Kevin; Sohn, Se Hui; Durazo, Armando; Sheng, Yuewei; Shaw, Bryan F.; Gralla, Edith Butler; Valentine, Joan Selverstone] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Sea, Kevin] Santa Rosa Jr Coll, Dept Wine Studies, Santa Rosa, CA 95401 USA. [Sohn, Se Hui] LG Chem Ltd, Taejon 305380, South Korea. [Durazo, Armando] Univ Arizona, Dept Chem & Environm Engn, Tucson, AZ 85721 USA. [Cabelli, Diane E.] Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. [Shaw, Bryan F.] Baylor Univ, Dept Chem & Biochem, Waco, TX 76798 USA. [Cao, Xiaohang; Taylor, Alexander B.; Whitson, Lisa J.; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. [Valentine, Joan Selverstone] Ewha Womans Univ, Dept Bioinspired Sci, Seoul 120750, South Korea. RP Sea, K (reprint author), Santa Rosa Jr Coll, Dept Wine Studies, 1501 Mendocino Ave, Santa Rosa, CA 95401 USA. EM kevinsea@yahoo.com; jsv@chem.ucla.edu RI Shaw, Bryan/A-7001-2008 FU National Institutes of Health [DK46828, GM28222, GM08496, NS39112]; Veterans Affairs [VA 101 BX00506]; U.S. Department of Energy Division of Chemical Sciences, Geosciences, and Biosciences [DE-AC02-98CH10886] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK46828 and GM28222 (to J. S. V.), GM08496 (to K. S.), and NS39112 (to P. J. H.). This work was also supported by Veterans Affairs Grant VA 101 BX00506 (to P. J. H.) and Contract DE-AC02-98CH10886 from the U.S. Department of Energy Division of Chemical Sciences, Geosciences, and Biosciences (to Brookhaven National Laboratory). NR 63 TC 6 Z9 6 U1 3 U2 27 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 23 PY 2015 VL 290 IS 4 BP 2405 EP 2418 DI 10.1074/jbc.M114.588798 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CA0EH UT WOS:000348588000043 PM 25433341 ER PT J AU Goroll, AH Hunt, DP AF Goroll, Allan H. Hunt, Daniel P. TI Bridging the Hospitalist-Primary Care Divide through Collaborative Care SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Goroll, Allan H.; Hunt, Daniel P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Goroll, AH (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. NR 5 TC 7 Z9 7 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 22 PY 2015 VL 372 IS 4 BP 308 EP 309 DI 10.1056/NEJMp1411416 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AZ4PJ UT WOS:000348204500005 PM 25607426 ER PT J AU Ansell, SM Lesokhin, AM Borrello, I Halwani, A Scott, EC Gutierrez, M Schuster, SJ Millenson, MM Cattry, D Freeman, GJ Rodig, SJ Chapuy, B Ligon, AH Zhu, LL Grosso, JF Kim, SY Timmerman, JM Shipp, MA Armand, P AF Ansell, Stephen M. Lesokhin, Alexander M. Borrello, Ivan Halwani, Ahmad Scott, Emma C. Gutierrez, Martin Schuster, Stephen J. Millenson, Michael M. Cattry, Deepika Freeman, Gordon J. Rodig, Scott J. Chapuy, Bjoern Ligon, Azra H. Zhu, Lili Grosso, Joseph F. Kim, Su Young Timmerman, John M. Shipp, Margaret A. Armand, Philippe TI PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STEM-CELL TRANSPLANTATION; T-CELLS; LYMPHOPROLIFERATIVE DISORDERS; ANTI-PD-1 ANTIBODY; RESPONSE CRITERIA; PHASE-II; CANCER; SAFETY; THERAPEUTICS; PIDILIZUMAB AB BACKGROUND Preclinical studies suggest that Reed-Sternberg cells exploit the programmed death 1 (PD-1) pathway to evade immune detection. In classic Hodgkin's lymphoma, alterations in chromosome 9p24.1 increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and promote their induction through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. We hypothesized that nivolumab, a PD-1-blocking antibody, could inhibit tumor immune evasion in patients with relapsed or refractory Hodgkin's lymphoma. METHODS In this ongoing study, 23 patients with relapsed or refractory Hodgkin's lymphoma that had already been heavily treated received nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks until they had a complete response, tumor progression, or excessive toxic effects. Study objectives were measurement of safety and efficacy and assessment of the PDL1 and PDL2 (also called CD274 and PDCD1LG2, respectively) loci and PD-L1 and PD-L2 protein expression. RESULTS Of the 23 study patients, 78% were enrolled in the study after a relapse following autologous stem-cell transplantation and 78% after a relapse following the receipt of brentuximab vedotin. Drug-related adverse events of any grade and of grade 3 occurred in 78% and 22% of patients, respectively. An objective response was reported in 20 patients (87%), including 17% with a complete response and 70% with a partial response; the remaining 3 patients (13%) had stable disease. The rate of progression-free survival at 24 weeks was 86%; 11 patients were continuing to participate in the study. Reasons for discontinuation included stem-cell transplantation (in 6 patients), disease progression (in 4 patients), and drug toxicity (in 2 patients). Analyses of pretreatment tumor specimens from 10 patients revealed copy-number gains in PDL1 and PDL2 and increased expression of these ligands. Reed-Sternberg cells showed nuclear positivity of phosphorylated STAT3, indicative of active JAK-STAT signaling. CONCLUSIONS Nivolumab had substantial therapeutic activity and an acceptable safety profile in patients with previously heavily treated relapsed or refractory Hodgkin's lymphoma. C1 [Ansell, Stephen M.] Mayo Clin, Rochester, MN 55905 USA. [Lesokhin, Alexander M.; Cattry, Deepika] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lesokhin, Alexander M.] Weill Cornell Med Coll, New York, NY 10021 USA. [Borrello, Ivan] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Borrello, Ivan] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Halwani, Ahmad] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Scott, Emma C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Scott, Emma C.] Knight Canc Inst, Portland, OR USA. [Gutierrez, Martin] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Zhu, Lili; Grosso, Joseph F.; Kim, Su Young] Bristol Myers Squibb Co, Lawrenceville, NJ USA. [Schuster, Stephen J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Millenson, Michael M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Freeman, Gordon J.; Chapuy, Bjoern; Shipp, Margaret A.; Armand, Philippe] Dana Farber Canc Inst, Boston, MA 02215 USA. [Rodig, Scott J.; Ligon, Azra H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Freeman, Gordon J.; Rodig, Scott J.; Chapuy, Bjoern; Ligon, Azra H.; Shipp, Margaret A.; Armand, Philippe] Harvard Univ, Sch Med, Boston, MA USA. [Timmerman, John M.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Ansell, SM (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. EM ansell.stephen@mayo.edu; philippe_armand@dfci.harvard.edu OI Halwani, Ahmad/0000-0001-6183-6491 FU Bristol-Myers Squibb; National Institutes of Health [U54CA163125, P01AI056299, R01CA161026]; Miller Fund; Seattle Genetics; Celldex Therapeutics; Millennium; Idera; Regeneron; Kyowa Hakko Kirin; AbbVie; Genentech; Ventana/Roche; Bayer; Gilead; Merck; Pharmacyclics; Janssen; Sanofi Aventis FX Supported by Bristol-Myers Squibb, by grants from the National Institutes of Health (U54CA163125 and P01AI056299, to Dr. Freeman; and R01CA161026, to Dr. Shipp), and by a grant from the Miller Fund (to Dr. Shipp).; Dr. Ansell reports receiving grant support from Seattle Genetics, Celldex Therapeutics, Millennium, Idera, and Regeneron; Dr. Lesokhin, receiving consulting fees and grant support from Bristol-Myers Squibb; Dr. Halwani, receiving grant support from Seattle Genetics, Millennium, Kyowa Hakko Kirin, AbbVie, Genentech, and Bristol-Myers Squibb; Dr. Freeman, receiving royalties from patents related to PD-1, PD-L1, and PD-L2 pathways (US 6808710, US 6936704, US 7038013, US7101550, US 7432059, US 7635757, US 7638492, US 7700301, US 7709214, US 8552154, and US 8652465), which are licensed to Bristol-Myers Squibb, Roche, Merck, EMD Serono, Boehringer Ingelheim, Amplimmune, and Novartis; Dr. Rodig, receiving grant support from Bristol-Myers Squibb and Ventana/Roche and having a pending patent application related to anti-PD-L1 monoclonal antibodies and fragments (US 61/895,543); Ms. Zhu, Dr. Grosso, and Dr. Kim, being employees of Bristol-Myers Squibb; Dr. Timmerman, receiving grant support from Bristol-Myers Squibb; Dr. Shipp, receiving fees for serving on advisory boards from Bristol-Myers Squibb, Bayer, Gilead, Merck, Pharmacyclics, and Janssen and receiving grant support from Bristol-Myers Squibb, Sanofi Aventis, and Bayer; and Dr. Armand, receiving consulting fees from Merck. No other potential conflict of interest relevant to this article was reported. NR 26 TC 595 Z9 622 U1 28 U2 101 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 22 PY 2015 VL 372 IS 4 BP 311 EP 319 DI 10.1056/NEJMoa1411087 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AZ4PJ UT WOS:000348204500006 PM 25482239 ER PT J AU David, WS Temin, ES Kraeft, JJ Hooper, DC AF David, William S. Temin, Elizabeth S. Kraeft, Jessica J. Hooper, David C. TI Case 3-2015: A 60-Year-Old Woman with Abdominal Pain, Dyspnea, and Diplopia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SUCCINYLCHOLINE-INDUCED HYPERKALEMIA; STATES C1 [David, William S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Temin, Elizabeth S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Kraeft, Jessica J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hooper, David C.] Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. [David, William S.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Temin, Elizabeth S.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Kraeft, Jessica J.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hooper, David C.] Harvard Univ, Sch Med, Dept Infect Dis, Boston, MA USA. RP David, WS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 22 PY 2015 VL 372 IS 4 BP 364 EP 372 DI 10.1056/NEJMcpc1410936 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AZ4PJ UT WOS:000348204500012 PM 25607430 ER PT J AU Xu, J Shao, Z Li, D Xie, HF Kim, W Huang, JL Taylor, JE Pinello, L Glass, K Jaffe, JD Yuan, GC Orkin, SH AF Xu, Jian Shao, Zhen Li, Dan Xie, Huafeng Kim, Woojin Huang, Jialiang Taylor, Jordan E. Pinello, Luca Glass, Kimberly Jaffe, Jacob D. Yuan, Guo-Cheng Orkin, Stuart H. TI Developmental Control of Polycomb Subunit Composition by GATA Factors Mediates a Switch to Non-Canonical Functions SO MOLECULAR CELL LA English DT Article ID HISTONE METHYLTRANSFERASE ACTIVITY; HEMATOPOIETIC STEM-CELLS; PROSTATE-CANCER; GENE-EXPRESSION; GROUP PROTEINS; LYSINE 27; IN-VIVO; EZH2; CHROMATIN; COMPLEX AB Polycomb repressive complex 2 (PRC2) plays crucial roles in transcriptional regulation and stem cell development. However, the context-specific functions associated with alternative subunits remain largely unexplored. Here we show that the related enzymatic subunits EZH1 and EZH2 undergo an expression switch during blood cell development. An erythroid-specific enhancer mediates transcriptional activation of EZH1, and a switch from GATA2 to GATA1 controls the developmental EZH1/2 switch by differential association with EZH1 enhancers. We further examine the in vivo stoichiometry of the PRC2 complexes by quantitative proteomics and reveal the existence of an EZH1-SUZ12 subcomplex lacking EED. EZH1 together with SUZ12 form a non-canonical PRC2 complex, occupy active chromatin, and positively regulate gene expression. Loss of EZH2 expression leads to repositioning of EZH1 to EZH2 targets. Thus, the lineage-and developmental stage-specific regulation of PRC2 subunit composition leads to a switch from canonical silencing to non-canonical functions during blood stem cell specification. C1 [Xu, Jian; Shao, Zhen; Xie, Huafeng; Kim, Woojin; Huang, Jialiang; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Xu, Jian; Shao, Zhen; Xie, Huafeng; Kim, Woojin; Huang, Jialiang; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Li, Dan] Harvard Univ, Cambridge, MA 02138 USA. [Huang, Jialiang; Pinello, Luca; Glass, Kimberly; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Taylor, Jordan E.; Jaffe, Jacob D.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Xu, Jian] Univ Texas SW Med Ctr Dallas, Dept Pediat, Childrens Res Inst, Dallas, TX 75390 USA. [Shao, Zhen] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Computat Biol, CAS MPG Partner Inst Computat Biol, Shanghai 200031, Peoples R China. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu FU NIH; NIDDK [K01DK093543, R03DK101665] FX We thank Sidinh Luc, Cong Peng, Matthew Canver, Daniel Bauer, and members of the S.H.O. laboratory for assistance and discussion; Ross Tomaino and Steven Gygi for assistance with proteomics analysis; and John Stamatoyannopoulos for assistance with DNase-seq. We thank Kambiz Mousavi and Vittorio Sartorelli for providing the EZH1 antibody, and Ben van Handel and Hanna Mikkola for providing the fetal liver CD34+ cells. This work was supported by funding from the NIH (G.-C.Y. and S.H.O.). S.H.O. is an Investigator of the Howard Hughes Medical Institute (HHMI). J.X. is supported by NIDDK Career Development Awards K01DK093543 and R03DK101665. NR 48 TC 24 Z9 24 U1 2 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD JAN 22 PY 2015 VL 57 IS 2 BP 304 EP 316 DI 10.1016/j.molcel.2014.12.009 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ9CC UT WOS:000348507800010 PM 25578878 ER PT J AU Kung, JT Kesner, B An, JY Ahn, JY Cifuentes-Rojas, C Colognori, D Jeon, Y Szanto, A del Rosario, BC Pinter, SF Erwin, JA Lee, JT AF Kung, Johnny T. Kesner, Barry An, Jee Young Ahn, Janice Y. Cifuentes-Rojas, Catherine Colognori, David Jeon, Yesu Szanto, Attila del Rosario, Brian C. Pinter, Stefan F. Erwin, Jennifer A. Lee, Jeannie T. TI Locus-Specific Targeting to the X Chromosome Revealed by the RNA Interactome of CTCF SO MOLECULAR CELL LA English DT Article ID BINDING PROTEINS; CHROMATIN INTERACTIONS; GENE-EXPRESSION; SEQ EXPERIMENTS; INACTIVATION; GENOME; CLIP; DNA; IDENTIFICATION; TRANSCRIPTION AB CTCF is a master regulator that plays important roles in genome architecture and gene expression. How CTCF is recruited in a locus-specific manner is not fully understood. Evidence from epigenetic processes, such as X chromosome inactivation (XCI), indicates that CTCF associates functionally with RNA. Using genome-wide approaches to investigate the relationship between its RNA interactome and epigenomic landscape, here we report that CTCF binds thousands of transcripts in mouse embryonic stem cells, many in close proximity to CTCF's genomic binding sites. CTCF is a specific and high-affinity RNA-binding protein (K-d < 1 nM). During XCI, CTCF differentially binds the active and inactive X chromosomes and interacts directly with Tsix, Xite, and Xist RNAs. Tsix and Xite RNAs target CTCF to the X inactivation center, thereby inducing homologous X chromosome pairing. Our work elucidates one mechanism by which CTCF is recruited in a locus-specific manner and implicates CTCF-RNA interactions in long-range chromosomal interactions. C1 [Kung, Johnny T.; Kesner, Barry; An, Jee Young; Ahn, Janice Y.; Cifuentes-Rojas, Catherine; Colognori, David; Jeon, Yesu; Szanto, Attila; del Rosario, Brian C.; Pinter, Stefan F.; Erwin, Jennifer A.; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Kung, Johnny T.; Kesner, Barry; An, Jee Young; Ahn, Janice Y.; Cifuentes-Rojas, Catherine; Colognori, David; Jeon, Yesu; Szanto, Attila; del Rosario, Brian C.; Pinter, Stefan F.; Erwin, Jennifer A.; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kung, Johnny T.; Kesner, Barry; An, Jee Young; Ahn, Janice Y.; Cifuentes-Rojas, Catherine; Colognori, David; Jeon, Yesu; Szanto, Attila; del Rosario, Brian C.; Pinter, Stefan F.; Erwin, Jennifer A.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ahn, Janice Y.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Pinter, Stefan/0000-0003-4750-1403; Ahn, Janice/0000-0003-3625-9906 FU Natural Sciences and Engineering Research Council of Canada; Michael and Anna Vranos Fellowship for the Life Sciences; NSF; NIH [F32-GM101828, RO1-GM58839] FX We thank all lab members for helpful advice and many important discussions. We also give special thanks to C.T. Wu, S. Buratowski, R. Reed, W. Bender, M. Blower, and P. Garrity for valuable advice during the thesis work of J.T.K, and C.T. Wu, R. Losick, and N. Francis during the thesis work of J.Y. Ahn. We acknowledge Exiqon Corporation for design of LNA oligonucleotides. This work was supported by a Postgraduate Scholarship from the Natural Sciences and Engineering Research Council of Canada (to J.T.K), a Michael and Anna Vranos Fellowship for the Life Sciences (to J.Y. Ahn), an NSF graduate fellowship (to J.A.E.), and NIH grants F32-GM101828 (to C.C.R.) and RO1-GM58839 (to J.T.L.). J.T.L. is an Investigator of the Howard Hughes Medical Institute. NR 61 TC 27 Z9 27 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD JAN 22 PY 2015 VL 57 IS 2 BP 361 EP 375 DI 10.1016/j.molcel.2014.12.006 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ9CC UT WOS:000348507800015 PM 25578877 ER PT J AU Savar, A Acin, S Gonzalez, CL El-Sawy, T Mejia, O Li, Z Esmaeli, B Lacy-Hulbert, A El-Naggar, AK McCarty, JH Caulin, C AF Savar, A. Acin, S. Gonzalez, C. L. El-Sawy, T. Mejia, O. Li, Z. Esmaeli, B. Lacy-Hulbert, A. El-Naggar, A. K. McCarty, J. H. Caulin, C. TI Loss of epithelial p53 and alpha v integrin cooperate through Akt to induce squamous cell carcinoma yet prevent remodeling of the tumor microenvironment SO ONCOGENE LA English DT Article DE p53; squamous cell carcinoma; mouse model; integrins; tumor microenvironment ID GAIN-OF-FUNCTION; ONCOGENIC K-RAS; SKIN-CANCER; ORGAN-TRANSPLANTATION; MOUSE MODEL; EXPRESSION; MUTATIONS; KERATINOCYTES; DIFFERENTIATION; INACTIVATION AB Most of the squamous cell carcinomas (SCCs) of the skin and head and neck contain p53 mutations. The presence of p53 mutations in premalignant lesions suggests that they represent early events during tumor progression and additional alterations may be required for SCC development. Here we show that codeletion of the p53 and alpha v integrin genes in mouse stratified epithelia induced SCCs in 100% of the mice, more frequently and with much shorter latency than deletion of either gene alone. The SCCs that lacked p53 and alpha v in the epithelial tumor cells exhibited high Akt activity, lacked multiple types of infiltrating immune cells, contained a defective vasculature and grew slower than tumors that expressed p53 or alpha v. These results reveal that loss of alpha v in epithelial cells that lack p53 promotes SCC development, but also prevents remodeling of the tumor microenvironment and delays tumor growth. We observed that Akt inactivation in SCC cells that lack p53 and alpha v promoted anoikis. Thus, tumors may arise in these mice as a result of the increased cell survival induced by Akt activation triggered by loss of alpha v and p53, and by the defective recruitment of immune cells to these tumors, which may allow immune evasion. However, the defective vasculature and lack of a supportive stroma create a restrictive microenvironment in these SCCs that slows their growth. These mechanisms may underlie the rapid onset and slow growth of SCCs that lack p53 and alpha v. C1 [Savar, A.; Acin, S.; Gonzalez, C. L.; El-Sawy, T.; Mejia, O.; Li, Z.; Esmaeli, B.; Caulin, C.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. [Lacy-Hulbert, A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [El-Naggar, A. K.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [McCarty, J. H.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Caulin, C.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. RP Caulin, C (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Unit 123, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM ccaulin@mdanderson.org FU National Institutes of Health [DE015344]; Pilot Project grant from the American Cancer Society Institutional Research Grant Program; National Institutes of Health through Cancer Center Support Grant [CA16672] FX We thank Dennis Roop for the K14.CrePR1 mice, Anton Berns for the floxed p53 mice and Sarah Bronson and Dawn Chalaire for editorial assistance. This study was supported by the National Institutes of Health through Grant DE015344 (C Caulin) and a Pilot Project grant from the American Cancer Society Institutional Research Grant Program (JH McCarty). Veterinary services and core facilities at The University of Texas MD Anderson Cancer Center were supported in part by the National Institutes of Health through Cancer Center Support Grant CA16672. NR 41 TC 4 Z9 4 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JAN 22 PY 2015 VL 34 IS 4 BP 516 EP 524 DI 10.1038/onc.2013.585 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AZ8FU UT WOS:000348451300012 PM 24469034 ER PT J AU Korn, D AF Korn, David TI Indirect costs: cash is no gravy train SO NATURE LA English DT Letter C1 [Korn, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Korn, David] Harvard Univ, Sch Med, Boston, MA USA. RP Korn, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM david_korn@harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 22 PY 2015 VL 517 IS 7535 BP 438 EP 438 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ4MU UT WOS:000348196500017 PM 25612045 ER PT J AU Tasnim, M Ma, SN Yang, EW Jiang, T Li, W AF Tasnim, Masruba Ma, Shining Yang, Ei-Wen Jiang, Tao Li, Wei TI Accurate inference of isoforms from multiple sample RNA-Seq data SO BMC GENOMICS LA English DT Article ID FUNCTIONAL ELEMENTS; SPLICE JUNCTIONS; IDENTIFICATION; REVEALS; GENOME; QUANTIFICATION; TRANSCRIPTOMES; PROJECT; READS AB Background: RNA-Seq based transcriptome assembly has become a fundamental technique for studying expressed mRNAs (i.e., transcripts or isoforms) in a cell using high-throughput sequencing technologies, and is serving as a basis to analyze the structural and quantitative differences of expressed isoforms between samples. However, the current transcriptome assembly algorithms are not specifically designed to handle large amounts of errors that are inherent in real RNA-Seq datasets, especially those involving multiple samples, making downstream differential analysis applications difficult. On the other hand, multiple sample RNA-Seq datasets may provide more information than single sample datasets that can be utilized to improve the performance of transcriptome assembly and abundance estimation, but such information remains overlooked by the existing assembly tools. Results: We formulate a computational framework of transcriptome assembly that is capable of handling noisy RNA-Seq reads and multiple sample RNA-Seq datasets efficiently. We show that finding an optimal solution under this framework is an NP-hard problem. Instead, we develop an efficient heuristic algorithm, called Iterative Shortest Path (ISP), based on linear programming (LP) and integer linear programming (ILP). Our preliminary experimental results on both simulated and real datasets and comparison with the existing assembly tools demonstrate that (i) the ISP algorithm is able to assemble transcriptomes with a greatly increased precision while keeping the same level of sensitivity, especially when many samples are involved, and (ii) its assembly results help improve downstream differential analysis. C1 [Tasnim, Masruba; Ma, Shining; Yang, Ei-Wen; Jiang, Tao; Li, Wei] Univ Calif Riverside, Dept Comp Sci & Engn, Riverside, CA 92507 USA. [Ma, Shining; Jiang, Tao] Tsinghua Univ, MOE Key Lab Bioinformat, TNLIST, Dept Automat, Beijing 100084, Peoples R China. [Ma, Shining] Tsinghua Univ, Bioinformat Div, TNLIST, Dept Automat, Beijing 100084, Peoples R China. [Jiang, Tao] Tsinghua Univ, Bioinformat Div, TNLIST, Dept Comp Sci & Technol, Beijing 100084, Peoples R China. [Li, Wei] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Wei] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Jiang, T (reprint author), Univ Calif Riverside, Dept Comp Sci & Engn, Riverside, CA 92507 USA. EM jiang@cs.ucr.edu; wli@jimmy.harvard.edu FU National Science Foundation [DBI-1262107] FX The research was partially supported by National Science Foundation grant DBI-1262107. NR 31 TC 2 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JAN 21 PY 2015 VL 16 SU 2 AR S15 DI 10.1186/1471-2164-16-S2-S15 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CH4CL UT WOS:000353978900015 PM 25708199 ER PT J AU Hu, ZT Vashlishan-Murray, AB Kaplan, JM AF Hu, Zhitao Vashlishan-Murray, Amy B. Kaplan, Joshua M. TI NLP-12 Engages Different UNC-13 Proteins to Potentiate Tonic and Evoked Release SO JOURNAL OF NEUROSCIENCE LA English DT Article DE C. elegans; CCK; Munc13; neuropeptide; NLP-12; UNC-13 ID ELEGANS NEUROMUSCULAR-JUNCTION; SHORT-TERM PLASTICITY; NEUROTRANSMITTER RELEASE; CAENORHABDITIS-ELEGANS; SYNAPTIC-TRANSMISSION; C-ELEGANS; VESICLE DOCKING; ACTIVE ZONES; G(Q)ALPHA; MUNC13-1 AB A neuropeptide (NLP-12) and its receptor (CKR-2) potentiate tonic and evoked ACh release at Caenorhabditis elegans neuromuscular junctions. Increased evoked release is mediated by a presynaptic pathway (egl-30 G alpha(q) and egl-8 PLC beta) that produces DAG, and by DAG binding to short and long UNC-13 proteins. Potentiation of tonic ACh release persists in mutants deficient for egl-30 G alpha(q) and egl-8 PLC beta and requires DAG binding to UNC-13L (but not UNC-13S). Thus, NLP-12 adjusts tonic and evoked release by distinct mechanisms. C1 [Hu, Zhitao; Vashlishan-Murray, Amy B.; Kaplan, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Hu, Zhitao; Vashlishan-Murray, Amy B.; Kaplan, Joshua M.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Vashlishan-Murray, Amy B.] Emerson Coll, Dept Commun Sci & Disorders, Boston, MA 02116 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Bldg,7th Floor,185 Cambridge St, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU National Institutes of Health [GM54728] FX This work was supported by a National Institutes of Health research grant (GM54728 to J.K.). We thank members of the Kaplan lab for critical comments on this manuscript. Some strains were provided by the C. elegans Genetics Stock Center. NR 44 TC 1 Z9 1 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 21 PY 2015 VL 35 IS 3 BP 1038 EP 1042 DI 10.1523/JNEUROSCI.2825-14.2015 PG 5 WC Neurosciences SC Neurosciences & Neurology GA CB1TU UT WOS:000349411700017 PM 25609620 ER PT J AU Lee, HG Milner, PJ Placzek, MS Buchwald, SL Hooker, JM AF Lee, Hong Geun Milner, Phillip J. Placzek, Michael S. Buchwald, Stephen L. Hooker, Jacob M. TI Virtually Instantaneous, Room-Temperature [C-11]-Cyanation Using Biaryl Phosphine Pd(0) Complexes SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PALLADIUM-CATALYZED CYANATION; RECEPTOR ANTAGONIST; PET; C-11 AB A new radiosynthetic protocol for the preparation of [C-11]aryl nitriles has been developed. This process is based on the direct reaction of in situ prepared L Pd(Ar)X complexes (L = biaryl phosphine) with [C-11]HCN. The strategy is operationally simple, exhibits a remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity compared to previously reported systems. With this procedure, a variety of [C-11]nitrile-containing pharmaceuticals were prepared with high radiochemical efficiency. C1 [Lee, Hong Geun; Milner, Phillip J.; Buchwald, Stephen L.] MIT, Cambridge, MA 02139 USA. [Placzek, Michael S.; Hooker, Jacob M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Placzek, Michael S.; Hooker, Jacob M.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Hooker, Jacob M.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. RP Buchwald, SL (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM sbuchwal@mit.edu; hooker@nmr.mgh.harvard.edu FU National Institutes of Health [GM46059]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health [P41EB015896]; National Institutes of Health Shared Instrumentation Grant Program; High-End Instrumentation Grant Program [S10RR017208, S10RR026666]; National Science Foundation [2010094243]; NIH-NIDA [2T32DA015036] FX Research reported in this publication was supported by the National Institutes of Health (GM46059). A portion of this research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Regional Resource supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the National Institutes of Health Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program (S10RR017208 and S10RR026666). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. P.J.M. thanks the National Science Foundation for a predoctoral fellowship (2010094243). We also thank Amgen for an educational donation. M.S.P. thanks NIH-NIDA for a postdoctoral fellowship (2T32DA015036). Technical assistance from Nathaniel Schauer, Judit Sore, and Dr. Ramesh Neelamegam (MGH/HST) is appreciated. We are grateful to Dr. Todd Senecal (MIT) for performing preliminary experiments. NR 18 TC 6 Z9 6 U1 1 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 21 PY 2015 VL 137 IS 2 BP 648 EP 651 DI 10.1021/ja5121155 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8RX UT WOS:000348483400025 PM 25565277 ER PT J AU Santillan-Hernandez, Y Almanza-Miranda, E Xin, WW Goss, K Vera-Loaiza, A Gorraez-de la Mora, MT Pina-Aguilar, RE AF Santillan-Hernandez, Yuritzi Almanza-Miranda, Enory Xin, Winnie W. Goss, Kendrick Vera-Loaiza, Aurea Gorraez-de la Mora, Maria T. Pina-Aguilar, Raul E. TI Novel LIPA mutations in Mexican siblings with lysosomal acid lipase deficiency SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Cholesteryl ester storage disease; Liver fibrosis; Dyslipidemia; Liver steatosis; Wolman disease ID ESTER STORAGE DISEASE AB Lysosomal acid lipase (LAL) deficiency is an under-recognized lysosomal disease caused by deficient enzymatic activity of LAL. In this report we describe two affected female Mexican siblings with early hepatic complications. At two months of age, the first sibling presented with alternating episodes of diarrhea and constipation, and later with hepatomegaly, elevated transaminases, high levels of total and low-density lipoprotein cholesterol, and low levels of high-density lipoprotein. Portal hypertension and grade 2 esophageal varices were detected at four years of age. The second sibling presented with hepatomegaly, elevated transaminases and mildly elevated low-density lipoprotein and low high-density lipoprotein at six months of age. LAL activity was deficient in both patients. Sequencing of LIPA revealed two previously unreported heterozygous mutations in exon 4: c. 253C>A and c. 294C>G. These cases highlight the clinical continuum between the so-called Wolman disease and cholesteryl ester storage disease, and underscore that LAL deficiency represents a single disease with a degree of clinical heterogeneity. C1 [Santillan-Hernandez, Yuritzi; Vera-Loaiza, Aurea] ISSSTE, Ctr Med Nacl Noviembre 20, Dept Med Genet, Mexico City 03100, DF, Mexico. [Almanza-Miranda, Enory] ISSSTE, Ctr Med Nacl Noviembre 20, Dept Pediat Gastroenterol, Mexico City 03229, DF, Mexico. [Xin, Winnie W.; Goss, Kendrick] Massachusetts Gen Hosp, Neurogenet DNA Diagnost Lab, Boston, MA 02114 USA. [Gorraez-de la Mora, Maria T.] ISSSTE, Ctr Med Nacl Noviembre 20, Dept Pathol, Mexico City 03100, DF, Mexico. [Pina-Aguilar, Raul E.] ISSSTE, Ctr Med Nacl Noviembre 20, Med Genom Div, Mexico City 03100, DF, Mexico. RP Pina-Aguilar, RE (reprint author), ISSSTE, Ctr Med Nacl Noviembre 20, Med Genom Div, San Lorenzo 502D,Col Valle, Mexico City 03100, DF, Mexico. EM rpina.a@hotmail.com OI Pina-Aguilar, Raul/0000-0002-2043-4282 NR 21 TC 0 Z9 0 U1 0 U2 0 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JAN 21 PY 2015 VL 21 IS 3 BP 1001 EP 1008 DI 10.3748/wjg.v21.i3.1001 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ7TA UT WOS:000348419400031 PM 25624737 ER PT J AU Hurwitz, M Williams, CL Mishra, P Rottmann, J Dhou, S Wagar, M Mannarino, EG Mak, RH Lewis, JH AF Hurwitz, Martina Williams, Christopher L. Mishra, Pankaj Rottmann, Joerg Dhou, Salam Wagar, Matthew Mannarino, Edward G. Mak, Raymond H. Lewis, John H. TI Generation of fluoroscopic 3D images with a respiratory motion model based on an external surrogate signal SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE respiration; lung motion; radiation therapy planning ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; GATED RADIOTHERAPY; RADIATION-THERAPY; XCAT PHANTOM; PATIENT DATA; TUMOR SIZE; RECONSTRUCTION; ACQUISITION; SIMULATION; PROJECTION AB Respiratory motion during radiotherapy can cause uncertainties in definition of the target volume and in estimation of the dose delivered to the target and healthy tissue. In this paper, we generate volumetric images of the internal patient anatomy during treatment using only the motion of a surrogate signal. Pre-treatment four-dimensional CT imaging is used to create a patient-specific model correlating internal respiratory motion with the trajectory of an external surrogate placed on the chest. The performance of this model is assessed with digital and physical phantoms reproducing measured irregular patient breathing patterns. Ten patient breathing patterns are incorporated in a digital phantom. For each patient breathing pattern, the model is used to generate images over the course of thirty seconds. The tumor position predicted by the model is compared to ground truth information from the digital phantom. Over the ten patient breathing patterns, the average absolute error in the tumor centroid position predicted by the motion model is 1.4 mm. The corresponding error for one patient breathing pattern implemented in an anthropomorphic physical phantom was 0.6 mm. The global voxel intensity error was used to compare the full image to the ground truth and demonstrates good agreement between predicted and true images. The model also generates accurate predictions for breathing patterns with irregular phases or amplitudes. C1 [Hurwitz, Martina] Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hurwitz, M (reprint author), Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. EM martinah@gmail.com; jhlewis@lroc.harvard.edu FU Varian Medical Systems, Inc.; Radiological Society of North America Research Scholar Grant [RSCH1206] FX The authors would like to thank Dr S Nishioka of the Department of Radiology, NTT Hospital, Sapporo, Japan, Dr H Shirato of the Department of Radiation Medicine, Hokkaido University School of Medicine, Sapporo, Japan, and Dr R Berbeco of Brigham and Women's Hospital, Boston, MA for sharing the patient tumor motion dataset with us. This project was supported, in part, through a Master Research Agreement with Varian Medical Systems, Inc. and Radiological Society of North America Research Scholar Grant #RSCH1206. NR 28 TC 2 Z9 2 U1 1 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2015 VL 60 IS 2 BP 521 EP 535 DI 10.1088/0031-9155/60/2/521 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AY6KL UT WOS:000347675100006 PM 25548999 ER PT J AU Grassberger, C Lomax, A Paganetti, H AF Grassberger, C. Lomax, Anthony Paganetti, H. TI Characterizing a proton beam scanning system for Monte Carlo dose calculation in patients SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE active scanning proton therapy; Monte Carlo simulation; patient dose calculation ID RANGE UNCERTAINTIES; THERAPY; TOPAS AB The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI). Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low-energy electrons (<0.6 MeV for 230 MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of-field effects such as secondary cancer induction. To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5 mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations. C1 [Grassberger, C.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Grassberger, C.; Lomax, Anthony] Harvard Univ, Sch Med, Boston, MA 02114 USA. Paul Scherrer Inst, Ctr Proton Radiotherapy, CH-5232 Villigen, Switzerland. RP Grassberger, C (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM Grassberger.Clemens@mgh.harvard.edu FU National Cancer Institute Grant [R01CA111590] FX The authors would like to acknowledge Dr Ben Clasie for sharing his knowledge about active scanning proton delivery systems, Dr Thomas Bortfeld for fruitful discussions concerning his analytical Bragg peak model and Dr Jon Jackson and Partners Research Computing for maintenance of the computing cluster. This work was supported by National Cancer Institute Grant R01CA111590. NR 20 TC 10 Z9 10 U1 1 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2015 VL 60 IS 2 BP 633 EP 645 DI 10.1088/0031-9155/60/2/633 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AY6KL UT WOS:000347675100012 PM 25549079 ER PT J AU Copik, AJ Baldys, A Nguyen, K Sahdeo, S Ho, H Kosaka, A Dietrich, PJ Fitch, B Raymond, JR Ford, APDW Button, D Milla, ME AF Copik, Alicja J. Baldys, Aleksander Nguyen, Khanh Sahdeo, Sunil Ho, Hoangdung Kosaka, Alan Dietrich, Paul J. Fitch, Bill Raymond, John R. Ford, Anthony P. D. W. Button, Donald Milla, Marcos E. TI Isoproterenol Acts as a Biased Agonist of the Alpha-1A-Adrenoceptor that Selectively Activates the MAPK/ERK Pathway SO PLOS ONE LA English DT Article ID PROTEIN-KINASE PATHWAYS; PAROTID ACINAR-CELLS; ALPHA(1)-ADRENERGIC RECEPTOR SUBTYPES; BETA-ADRENERGIC-RECEPTORS; TRANSFECTED PC12 CELLS; BETA(2)-ADRENERGIC RECEPTOR; ALPHA(1A)-ADRENERGIC RECEPTORS; INTERNALIZATION PROPERTIES; SYMPATHOMIMETIC AMINES; FUNCTIONAL SELECTIVITY AB The alpha(1A)-AR is thought to couple predominantly to the G alpha(q)/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e. not all agonists of a given GPCR generate responses through utilization of the same signaling cascade(s). Previous work with G alpha(q) coupling-defective variants of alpha(1A)-AR, as well as a combination of Ca2+ channel blockers, uncovered cross-talk between alpha(1A)-AR and beta(2)-AR that leads to potentiation of a G alpha(q)-independent signaling cascade in response to alpha(1A)-AR activation. We hypothesized that molecules exist that act as biased agonists to selectively activate this pathway. In this report, isoproterenol (Iso), typically viewed as beta-AR-selective agonist, was examined with respect to activation of alpha(1A)-AR. alpha(1A)-AR selective antagonists were used to specifically block Iso evoked signaling in different cellular backgrounds and confirm its action at alpha(1A)-AR. Iso induced signaling at alpha(1A)-AR was further interrogated by probing steps along the G alpha(q)/PLC, G alpha(s) and MAPK/ERK pathways. In HEK-293/EBNA cells transiently transduced with alpha(1A)-AR, and CHO_alpha(1A)-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+ mobilization that could be blocked by alpha(1A)-AR selective antagonists. The kinetics of Iso induced Ca2+ transients differed from typical G alpha(q)-mediated Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could be detected in either cell line after stimulation with Iso, but activation was accompanied by receptor internalization. Data are presented that indicate that Iso represents a novel type of alpha(1A)-AR partial agonist with signaling bias toward MAPK/ERK signaling cascade that is likely independent of coupling to G alpha(q). C1 [Copik, Alicja J.; Sahdeo, Sunil; Ford, Anthony P. D. W.; Button, Donald; Milla, Marcos E.] Roche Palo Alto LLC, Biochem Pharmacol Inflammat Discovery, Palo Alto, CA 94304 USA. [Nguyen, Khanh; Ho, Hoangdung; Kosaka, Alan; Dietrich, Paul J.; Fitch, Bill] Roche Palo Alto LLC, Discovery Technol, Palo Alto, CA 94304 USA. [Baldys, Aleksander; Raymond, John R.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Baldys, Aleksander; Raymond, John R.] Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC 29425 USA. RP Milla, ME (reprint author), Roche Palo Alto LLC, Biochem Pharmacol Inflammat Discovery, 3401 Hillview Dr, Palo Alto, CA 94304 USA. EM mmilla22@its.jnj.com FU Department of Veterans Affairs Merit and Research Enhancement Award Program grants; National Institutes of Health [DK052448, GM063909]; Medical University of South Carolina Division of Nephrology, and Dialysis Clinics, Inc.; Roche Palo Alto LLC FX Most of this work was performed at Roche Palo Alto LLC. Immunofluorescence microscopy studies were performed with support from the Department of Veterans Affairs Merit and Research Enhancement Award Program grants, by National Institutes of Health Grants DK052448 and GM063909, by laboratory endowment jointly supported by the Medical University of South Carolina Division of Nephrology, and Dialysis Clinics, Inc. (to JRR). Roche Palo Alto LLC, the funder, provided support in the form of salaries for authors AJC, KN, SS, HH, AK, PJD, BF, APDWF, DB and MEM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section. NR 69 TC 2 Z9 2 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 21 PY 2015 VL 10 IS 1 AR e0115701 DI 10.1371/journal.pone.0115701 PG 31 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ4PR UT WOS:000348205300018 PM 25606852 ER PT J AU Penagarikano, O Lazaro, MT Lu, XH Gordon, A Dong, HM Lam, HA Peles, E Maidment, NT Murphy, NP Yang, XW Golshani, P Geschwind, DH AF Penagarikano, Olga Lazaro, Maria T. Lu, Xiao-Hong Gordon, Aaron Dong, Hongmei Lam, Hoa A. Peles, Elior Maidment, Nigel T. Murphy, Niall P. Yang, X. William Golshani, Peyman Geschwind, Daniel H. TI Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID RECEPTOR GENE OXTR; SPECTRUM DISORDER; PLASMA OXYTOCIN; PRAIRIE VOLES; AFFILIATIVE BEHAVIOR; MICROTUS-OCHROGASTER; HYPERPHAGIC OBESITY; MICE; VASOPRESSIN; RELEASE AB Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2), in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome, displays many features that parallel those of the human disorder. Because CDFE has high penetrance for autism spectrum disorder (ASD), we performed an in vivo screen for drugs that ameliorate abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the para-ventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment to rectify this deficit. C1 [Penagarikano, Olga; Lazaro, Maria T.; Dong, Hongmei; Golshani, Peyman; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA. [Penagarikano, Olga; Geschwind, Daniel H.] Univ Calif Los Angeles, Ctr Autism Res & Treament, Los Angeles, CA 90095 USA. [Penagarikano, Olga; Geschwind, Daniel H.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Lu, Xiao-Hong; Yang, X. William; Geschwind, Daniel H.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Gordon, Aaron; Peles, Elior] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. [Lam, Hoa A.; Maidment, Nigel T.; Murphy, Niall P.] Univ Calif Los Angeles, Jane & Terry Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Golshani, Peyman] Univ Calif Los Angeles, Integrat Ctr Learning & Memory, Los Angeles, CA 90095 USA. [Golshani, Peyman] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Geschwind, DH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA. EM dhg@ucla.edu OI Penagarikano, Olga/0000-0001-8153-8221 FU NIH/National Institute of Mental Health (NIMH) [R01 MH081754-02R, NIH/NS50220]; NIH Autism Centers of Excellence (ACE) (Project II) [1P50-HD055784-01]; Simons Foundation Autism Research Initiative; UCLA Center for Autism Research and Treatment (CART) Pilot Grant; Autism Speaks grant in translational research [7657]; NIH/National Institute of Neurological Disorders and Stroke (NINDS) [R01 NS049501, R01 NS074312]; McKnight Foundation; [5R01-MH081754-04] FX This work was supported by grants NIH/National Institute of Mental Health (NIMH) R01 MH081754-02R to D.H.G., NIH/NS50220 to E.P., NIH Autism Centers of Excellence (ACE) 1P50-HD055784-01 to D.H.G. (Project II), Network grant 5R01-MH081754-04 to D.H.G., Simons Foundation Autism Research Initiative to E.P. and D.H.G., UCLA Center for Autism Research and Treatment (CART) Pilot Grant to N.T.M. and N.P.M., and Autism Speaks grant in translational research 7657 to O.P. X.W.Y. is supported by the NIH/National Institute of Neurological Disorders and Stroke (NINDS) grants R01 NS049501 and R01 NS074312, and the Brain Disorder Award from McKnight Foundation. NR 76 TC 50 Z9 51 U1 4 U2 32 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 21 PY 2015 VL 7 IS 271 AR 271ra8 DI 10.1126/scitranslmed.3010257 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AZ6TS UT WOS:000348353900002 PM 25609168 ER PT J AU Chen, XQ Wales, P Quinti, L Zuo, FX Moniot, S Herisson, F Rauf, NA Wang, H Silverman, RB Ayata, C Maxwell, MM Steegborn, C Schwarzschild, MA Outeiro, TF Kazantsev, AG AF Chen, Xiqun Wales, Pauline Quinti, Luisa Zuo, Fuxing Moniot, Sebastien Herisson, Fanny Rauf, Nazifa Abdul Wang, Hua Silverman, Richard B. Ayata, Cenk Maxwell, Michelle M. Steegborn, Clemens Schwarzschild, Michael A. Outeiro, Tiago F. Kazantsev, Aleksey G. TI The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson's Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia SO PLOS ONE LA English DT Article ID MOUSE MODEL; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; SIRT2; DEACETYLASE; ALS; PROTEIN; NEURODEGENERATION; POLYMORPHISM; GENERATION AB Sirtuin deacetylases regulate diverse cellular pathways and influence disease processes. Our previous studies identified the brain-enriched sirtuin-2 (SIRT2) deacetylase as a potential drug target to counteract neurodegeneration. In the present study, we characterize SIRT2 inhibition activity of the brain-permeable compound AK7 and examine the efficacy of this small molecule in models of Parkinson's disease, amyotrophic lateral sclerosis and cerebral ischemia. Our results demonstrate that AK7 is neuroprotective in models of Parkinson's disease; it ameliorates alpha-synuclein toxicity in vitro and prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine depletion and dopaminergic neuron loss in vivo. The compound does not show beneficial effects in mouse models of amyotrophic lateral sclerosis and cerebral ischemia. These findings underscore the specificity of protective effects observed here in models of Parkinson's disease, and previously in Huntington's disease, and support the development of SIRT2 inhibitors as potential therapeutics for the two neurodegenerative diseases. C1 [Chen, Xiqun; Quinti, Luisa; Zuo, Fuxing; Herisson, Fanny; Rauf, Nazifa Abdul; Ayata, Cenk; Maxwell, Michelle M.; Schwarzschild, Michael A.; Kazantsev, Aleksey G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. [Wales, Pauline; Outeiro, Tiago F.] Univ Med Ctr Goettingen, Ctr Nanoscale Microscopy & Mol Physiol Brain, Dept NeuroDegenerat & Restorat Res, D-37073 Gottingen, Germany. [Moniot, Sebastien; Steegborn, Clemens] Univ Bayreuth, Dept Biochem, D-95447 Bayreuth, Germany. [Wang, Hua; Silverman, Richard B.] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chem Life Proc Inst, Dept Chem,Dept Mol Biosci, Evanston, IL 60208 USA. RP Chen, XQ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. EM xchen17@mgh.harvard.edu; AKAZANTSEV@mgh.harvard.edu FU NIH [U01-NS066912]; RJG foundation [2011D004473]; DFG Center of Excellence on Nanoscale Microscopy and Molecular Physiology of the Brain FX This work was supported by grants from the NIH U01-NS066912 (http://grants.nih.gov/grants/funding/ac_search_results.htm?text_curr = u01), RJG foundation 2011D004473 (no website), and DFG Center of Excellence on Nanoscale Microscopy and Molecular Physiology of the Brain (http://grc.unigoettingen.de/89.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 19 Z9 19 U1 3 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 21 PY 2015 VL 10 IS 1 AR UNSP e0116919 DI 10.1371/journal.pone.0116919 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ4PR UT WOS:000348205300044 ER PT J AU Bendell, JC Powderly, JD Lieu, CH Eckhardt, SG Hurwitz, H Hochster, HS Murphy, JE Funke, RP Rossi, C Wallin, J Waterkamp, D Pishvaian, MJ AF Bendell, Johanna C. Powderly, John D. Lieu, Christopher Hanyoung Eckhardt, S. Gail Hurwitz, Herbert Hochster, Howard S. Murphy, Janet E. Funke, Roel Peter Rossi, Cheryl Wallin, Jeffrey Waterkamp, Daniel Pishvaian, Michael J. TI Safety and efficacy of MPDL3280A (anti-PDL1) in combination with bevacizumab (bev) and/or FOLFOX in patients (pts) with metastatic colorectal cancer (mCRC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. Carolina BioOncol Inst, Huntersville, NC USA. Univ Colorado, Denver, CO 80202 USA. Univ Colorado, Sch Med, Aurora, CO USA. Duke Univ, Med Ctr, Durham, NC USA. Yale Univ, Sch Med, Dept Med Oncol, New Haven, CT USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Genentech Inc, San Francisco, CA 94080 USA. F Hoffmann La Roche Ltd, Basel, Switzerland. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 704 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800699 ER PT J AU Castillo, JJ Glezerman, I Boklage, S Chiodo, J Schulman, KL AF Castillo, Jorge J. Glezerman, Ilya Boklage, Susan Chiodo, Joseph Schulman, Kathy L. TI Incidence of hyponatremia in a cohort of patients with colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Weill Cornell Med Coll, New York, NY USA. Otsuka Amer Pharmaceut Inc, Princeton, NJ USA. Outcomes Res Solutions Inc, Shrewsbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 545 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800542 ER PT J AU Chong, DQ Mehta, R Song, MY Kedrin, D Meyerhardt, JA Ng, K Wu, K Ogino, S Fuchs, CS Giovannucci, EL Chan, AT AF Chong, Dawn Q. Mehta, Raaj Song, Mingyang Kedrin, Dmitriy Meyerhardt, Jeffrey A. Ng, Kimmie Wu, Kana Ogino, Shuji Fuchs, Charles S. Giovannucci, Edward L. Chan, Andrew T. TI Prediagnostic plasma adiponectin and survival among patients with colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Natl Canc Ctr, Singapore, Singapore. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Channing Labs, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, TH Chan Sch Publ Hlth, Sch Med, Boston, MA 02115 USA. RI Song, Mingyang/M-6701-2013 OI Song, Mingyang/0000-0002-1324-0316 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 526 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800523 ER PT J AU Coart, E Saad, ED Shi, Q Sommeijer, DW Zalcberg, JR Maughan, T Goldberg, RM Schmoll, HJ Punt, CJA Van Cutsem, E Douillard, JY Hoff, PM Tebbutt, NC Fuchs, CS Falcone, A Tournigand, C De Gramont, A Sargent, DJ Burzykowski, T Buyse, ME AF Coart, Elisabeth Saad, Everardo D. Shi, Qian Sommeijer, Dirkje Willemien Zalcberg, John Raymond Maughan, Tim Goldberg, Richard M. Schmoll, Hans-Joachim Punt, Cornelis J. A. Van Cutsem, Eric Douillard, Jean-Yves Hoff, Paulo Marcelo Tebbutt, Niall C. Fuchs, Charles S. Falcone, Alfredo Tournigand, Christophe De Gramont, Aimery Sargent, Daniel J. Burzykowski, Tomasz Buyse, Marc E. CA ARCAD Grp TI Trial-level association between response-based endpoints (RBEs) and progression-free (PFS)/overall survival (OS) in first-line therapy for metastatic colorectal cancer (mCRC) in the ARCAD database. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Int Inst Drug Dev, Louvain, Belgium. Dendrix Res, Sao Paulo, Brazil. Mayo Clin, Rochester, MN USA. Univ Amsterdam, Acad Med Ctr, NHMRC Clin Trials Ctr, Flevohosp, NL-1105 AZ Amsterdam, Netherlands. Monash Univ, Sch Publ Hlth, Melbourne, Vic 3004, Australia. CRUK MRC Oxford Inst Radiat Oncol, Oxford, England. Ohio State Univ Wexner Med Ctr, Columbus, OH USA. Univ Clin Halle Saale, Dept Internal Med 4, Halle, Germany. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. Univ Hosp Gasthuisberg Leuven, Leuven, Belgium. Ctr Rene Gauducheau, Dept Med Oncol, F-44035 Nantes, France. Univ Sao Paulo, Hosp Sirio Libanes, Sao Paulo, Brazil. Univ Sao Paulo, Inst Canc Estado Sao Paulo, Sao Paulo, Brazil. Austin Hlth, Melbourne, Vic, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Azienda Osped Univ Pisana Ist Toscano Tumori, UO Oncol Med 2, Pisa, Italy. Hop Henri Mondor, UPEC, F-94010 Creteil, France. Hosp St Antoine, Paris, France. Int Inst Drug Dev, Leuven, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 666 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800661 ER PT J AU Demetri, GD Reichardt, P Kang, YK Blay, JY Joensuu, H Schaefer, KB Kuss, I Kappeler, C Casali, PG AF Demetri, George D. Reichardt, Peter Kang, Yoon-Koo Blay, Jean-Yves Joensuu, Heikki Schaefer, Klaus Bernd Kuss, Iris Kappeler, Christian Casali, Paolo Giovanni TI An updated overall survival analysis with correction for protocol-planned crossover of the international, phase III, randomized, placebo-controlled trial of regorafenib in advanced gastrointestinal stromal tumors after failure of imatinib and sunitinib (GRID). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. HELIOS Klinikum Berlin Buch, Berlin, Germany. Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. Ctr Leon Berard, F-69373 Lyon, France. Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Helsinki, Finland. Bayer Pharma AG, Berlin, Germany. Bayer HealthCare Pharmaceut, Berlin, Germany. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 110 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800108 ER PT J AU Fuentes, E Ahmad, R Hong, TS Clark, JW Kwak, EL Rattner, DW Mullen, JT AF Fuentes, Eva Ahmad, Rima Hong, Theodore S. Clark, Jeffrey W. Kwak, Eunice Lee Rattner, David W. Mullen, John Thomas TI The impact of neoadjuvant therapy for gastroesophageal adenocarcinoma on postoperative morbidity and mortality SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 156 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800154 ER PT J AU Goyal, L Yurgelun, MB Abrams, TA Kwak, EL Cleary, JM Knowles, M Regan, E Gisondi, A Sheehan, S Zheng, H Zhu, AX AF Goyal, Lipika Yurgelun, Matthew B. Abrams, Thomas Adam Kwak, Eunice Lee Cleary, James M. Knowles, Michelle Regan, Eileen Gisondi, Amy Sheehan, Susan Zheng, Hui Zhu, Andrew X. TI A phase II trial of cabozantinib (XL-184) in patients with advanced cholangiocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MGH Canc Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 800 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800795 ER PT J AU Hatziapostolou, M Koutsioumpa, M Kottakis, F Iliopoulos, D Polytarchou, C AF Hatziapostolou, Maria Koutsioumpa, Marina Kottakis, Filippos Iliopoulos, Dimitrios Polytarchou, Christos TI Targeting colon cancer metabolism through a long noncoding RNA. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Syst Biomed, Div Digest Dis, Los Angeles, CA 90095 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 604 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800601 ER PT J AU Isakoff, SJ Saleh, MN Lugovskoy, A Mathews, S Czibere, AG Shields, AF Bahleda, R Soria, JC Arnedos, M AF Isakoff, Steven J. Saleh, Mansoor N. Lugovskoy, Alexey Mathews, Sara Czibere, Akos Gabor Shields, Anthony Frank Bahleda, Rastislav Soria, Jean-Charles Arnedos, Monica TI First-in-human study of MM-141: A novel tetravalent monoclonal antibody targeting IGF-1R and ErbB3. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Georgia Canc Specialists PC, Atlanta, GA USA. Merrimack Pharmaceut Inc, Cambridge, MA USA. Karmanos Canc Inst, Detroit, MI USA. Inst Gustave Roussy, Drug Dev Dept, Villejuif, France. Inst Gustave Roussy, Villejuif, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 384 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800382 ER PT J AU Kwak, EL LoRusso, P Hamid, O Janku, F Kittaneh, M Catenacci, DVT Chan, E Bekaii-Saab, TS Amore, B Hwang, YC Tang, R Ngarmchamnanrith, G Hong, DS AF Kwak, Eunice Lee LoRusso, Patricia Hamid, Omid Janku, Filip Kittaneh, Muaiad Catenacci, Daniel Virgil Thomas Chan, Emily Bekaii-Saab, Tanios S. Amore, Benny Hwang, Yuying C. Tang, Rui Ngarmchamnanrith, Gataree Hong, David S. TI Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Yale Canc Ctr, New Haven, CT USA. Angeles Clin & Res Inst, Los Angeles, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Karmanos Canc Inst, Detroit, MI USA. Univ Chicago, Chicago, IL 60637 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Ohio State Univ, Ctr Comprehens Canc, Arthur G James Canc Hosp, Columbus, OH 43210 USA. Richard J Solove Res Inst, Columbus, OH USA. Amgen Inc, Seattle, WA USA. Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 1 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800002 ER PT J AU Olszanski, AJ Wang-Gillam, A Kwak, EL Nazzal, K Mehdi, F Borad, MJ AF Olszanski, Anthony J. Wang-Gillam, Andrea Kwak, Eunice Lee Nazzal, Kamal Mehdi, Fazal Borad, Mitesh J. TI A phase I dose-escalation trial of TH-302 with nab-paclitaxel and gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Temple Hlth, Fox Chase Canc Ctr, Philadelphia, PA USA. Washington Univ, St Louis, MO USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. EMD Serono, Billerica, MA USA. Mayo Clin, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA TPS505 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800503 ER PT J AU Tabernero, J Ohtsu, A Muro, K Van Cutsem, E Oh, SC Bodoky, G Shimada, Y Hironaka, S Ajani, JA Tomasek, J Safran, H Chandrawansa, K Hsu, YZ Heathman, M Khan, AZ Ni, L Melemed, AS Gao, L Ferry, D Fuchs, CS AF Tabernero, Josep Ohtsu, Atsushi Muro, Kei Van Cutsem, Eric Oh, Sang Cheul Bodoky, Gyorgy Shimada, Yasuhiro Hironaka, Shuichi Ajani, Jaffer A. Tomasek, Jiri Safran, Howard Chandrawansa, Kumari Hsu, Yanzhi Heathman, Michael Khan, Azhar Z. Ni, Lan Melemed, Allen S. Gao, Ling Ferry, David Fuchs, Charles S. TI Exposure-response (E-R) relationship of ramucirumab (RAM) from two global, randomized, double-blind, phase 3 studies of patients (Pts) with advanced second-line gastric cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Vall dHebron Univ Hosp, Barcelona, Spain. Natl Canc Ctr, Exploratory Oncol Res & Clin Trial Ctr, Kashiwa, Chiba, Japan. Aichi Canc Ctr Hosp, Dept Clin Oncol, Nagoya, Aichi 464, Japan. Univ Hosp Gasthuisberg Leuven, Leuven, Belgium. Korea Univ, Guro Hosp, Seoul, South Korea. Szent Laszlo Hosp, Budapest, Hungary. Natl Canc Ctr, Tokyo, Japan. Chiba Canc Ctr, Clin Trial Promot Dept, Chiba 2608717, Japan. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Masaryk Univ, Fac Med, Masaryk Mem Canc Inst, Brno, Czech Republic. Brown Univ, Oncol Res Grp, Providence, RI 02912 USA. Eli Lilly & Co, Bridgewater, NJ USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 121 PG 2 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800119 ER PT J AU Yao, JC Buzzoni, R Carnaghi, C Fazio, N Singh, S Wolin, EM Tomasek, J Raderer, M Lahner, H Lam, DH Cauwel, H Valle, JW Delle Fave, G Van Cutsem, E Strosberg, JR Tesselaar, ME Shimada, Y Oh, DY Kulke, M Pavel, ME AF Yao, James C. Buzzoni, Roberto Carnaghi, Carlo Fazio, Nicola Singh, Simron Wolin, Edward M. Tomasek, Jiri Raderer, Markus Lahner, Harald Lam, Du Hung Cauwel, Helene Valle, Juan W. Delle Fave, Gianfranco Van Cutsem, Eric Strosberg, Jonathan R. Tesselaar, Margot Et Shimada, Yasuhiro Oh, Do-Youn Kulke, Matthew Pavel, Marianne E. CA Fourth Trial RADIANT-4 Study Grp TI Baseline demographics of the randomized, placebo-controlled, double-blind, phase III RADIANT-4 study of everolimus in nonfunctional gastrointestinal (GI) or lung neuroendocrine tumors (NET). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. IRCCS Ist Clin Humanitas, Rozzano, Italy. Ist Europeo Oncol, Milan, Italy. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Univ Kentucky, Markey Canc Ctr, Lexington, KY USA. Masaryk Univ, Masaryk Mem Canc Inst, Fac Med, Brno, Czech Republic. AKH, Univ Klin Innere Med 1, Vienna, Austria. Univ Klinikum Essen, Zentrum Innere Med, Essen, Germany. Novartis Pharmaceut, E Hanover, NJ USA. Novartis Pharma AG, Basel, Switzerland. Univ Manchester, Manchester Acad Hlth Sci Ctr, Dept Med Oncol, Christie NHS Fdn Trust, Manchester, Lancs, England. Univ Roma La Sapienza, Azienda Osped St Andrea, Rome, Italy. Univ Hosp Gasthuisberg Leuven, Leuven, Belgium. Univ S Florida, H Lee Moffitt Canc Ctr, Dept Med, Tampa, FL 33682 USA. Netherlands Canc Inst, Amsterdam, Netherlands. Natl Canc Ctr, Tokyo, Japan. Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Dana Farber Canc Inst, Boston, MA 02115 USA. Charite, Campus Virchow Klinikum, D-13353 Berlin, Germany. RI Valle, Juan/J-3571-2015 OI Valle, Juan/0000-0002-1999-0863 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 276 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800274 ER PT J AU Zhu, AX Ryoo, BY Yen, CJ Kudo, M Poon, RTP Pastorelli, D Blanc, JF Chung, HC Baron, AD Pfiffer, TEF Okusaka, T Kubackova, K Trojan, J Sastre, J Chau, I Chang, SC Abada, P Yang, L Hsu, Y Park, JO AF Zhu, Andrew X. Ryoo, Baek-Yeol Yen, Chia-Jui Kudo, Masatoshi Poon, Ronnie Tung-Ping Pastorelli, Davide Blanc, Jean-Frederic Chung, Hyun Cheol Baron, Ari David Pfiffer, Tulio Eduardo Flesch Okusaka, Takuji Kubackova, Katerina Trojan, Jorg Sastre, Javier Chau, Ian Chang, Shao-Chun Abada, Paolo Yang, Ling Hsu, Yanzhi Park, Joon Oh TI Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): Analysis of patients with elevated alpha-fetoprotein (AFP) from the randomized phase III REACH study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. Univ Ulsan Coll Med, Dept Oncol, Asan Med Ctr, Seoul, South Korea. Natl Cheng Kung Univ Hosp, Internal Med, Tainan 70428, Taiwan. Kinki Univ Sch Med, Dept Gastroenterol & Hepatol, Osaka, Japan. Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China. IRCCS, Oncol Med 1, Ist Oncol Veneto, Padua, Italy. Hop St Andre, Bordeaux, France. Yonsei Univ Coll Med, Yonsei Canc Ctr, Canc Metastasis Res Ctr, Shinchon Dong, South Korea. Pacific Hematol Oncol Associates, San Francisco, CA USA. Inst Canc Estado Sao Paulo, Sao Paulo, Brazil. Natl Canc Ctr, Div Hepatobiliary & Pancreat Oncol, Tokyo, Japan. Charles Univ Prague, Univ Hosp Motol, Dept Oncol, Prague, Czech Republic. Goethe Univ Frankfurt, D-60054 Frankfurt, Germany. Hosp Clin San Carlos, Madrid, Spain. Royal Marsden NHS Fdn Trust, London, England. Royal Marsden NHS Fdn Trust, Surrey, England. Eli Lilly & Co, Indianapolis, IN 46285 USA. Eli Lilly & Co, Bridgewater, NJ USA. Sungkyunkwan Univ, Samsung Med Ctr, Seoul, South Korea. NR 0 TC 3 Z9 3 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 232 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800230 ER PT J AU Munoz, JL Rodriguez-Cruz, V Ramkissoon, SH Ligon, KL Greco, SJ Rameshwar, P AF Munoz, Jessian L. Rodriguez-Cruz, Vivian Ramkissoon, Shakti H. Ligon, Keith L. Greco, Steven J. Rameshwar, Pranela TI Temozolomide resistance in glioblastoma occurs by miRNA-9-targeted PTCH1, independent of sonic hedgehog level SO ONCOTARGET LA English DT Article DE glioblastoma; MicroRNA-9; PTCH; Temozolomide; P-gp ID BREAST-CANCER CELLS; STEM-CELLS; EXPRESSION; MICRORNAS; INHIBITION; DELIVERY; DIFFERENTIATION; NEUROGENESIS; ACTIVATION; MUTATIONS AB Glioblastoma Multiforme (GBM), the most common and lethal adult primary tumor of the brain, showed a link between Sonic Hedgehog (SHH) pathway in the resistance to temozolomide (TMZ). PTCH1, the SHH receptor, can tonically represses signaling by endocytosis. We asked how the decrease in PTCH1 in GBM cells could lead to TMZ-resistance. TMZ resistant GBM cells have increased PTCH1 mRNA and reduced protein. Knockdown of Dicer, a Type III RNAase, indicated that miRNAs can explain the decreased PTCH1 in TMZ resistant cells. Computational studies, real-time PCR, reporter gene studies, western blots, target protector oligos and ectopic expression identified miR-9 as the target of PTCH1 in resistant GBM cells with concomitant activation of SHH signaling. MiR-9 mediated increases in the drug efflux transporters, MDR1 and ABCG2. MiR-9 was increased in the tissues from GBM patients and in an early passage GBM cell line from a patient with recurrent GBM but not from a naive patient. Pharmacological inhibition of SHH signaling sensitized the GBM cells to TMZ. Taken together, miR-9 targets PTCH1 in GBM cells by a SHH-independent method in GBM cells for TMZ resistance. The identified pathways could lead to new strategies to target GBM with combinations of drugs. C1 [Munoz, Jessian L.; Greco, Steven J.; Rameshwar, Pranela] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Munoz, Jessian L.; Rameshwar, Pranela] Rutgers Sch Biomed Hlth Sci, Grad Sch Biomed Sci, Newark, NJ USA. [Rodriguez-Cruz, Vivian] Univ Puerto Rico, Dept Chem, Cayey, PR USA. [Ramkissoon, Shakti H.; Ligon, Keith L.] Boston Childrens Hosp, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Ramkissoon, Shakti H.; Ligon, Keith L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Rameshwar, P (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, 185 S Orange Ave, Newark, NJ 07103 USA. EM rameshwa@njms.rutgers.edu FU F.M Kirby FX This work was supported by F.M Kirby to PR. NR 36 TC 12 Z9 14 U1 1 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 20 PY 2015 VL 6 IS 2 BP 1190 EP 1201 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CF4AE UT WOS:000352489800048 PM 25595896 ER PT J AU Berg, A Hoivik, EA Mjos, S Holst, F Werner, HMJ Tangen, IL Taylor-Weiner, A Gibson, WJ Kusonmano, K Wik, E Trovik, J Halle, MK Oyan, AM Kalland, KH Cherniack, AD Beroukhim, R Stefansson, I Mills, GB Krakstad, C Salvesen, HB AF Berg, Anna Hoivik, Erling A. Mjos, Siv Holst, Frederik Werner, Henrica M. J. Tangen, Ingvild L. Taylor-Weiner, Amaro Gibson, William J. Kusonmano, Kanthida Wik, Elisabeth Trovik, Jone Halle, Mari K. Oyan, Anne M. Kalland, Karl-Henning Cherniack, Andrew D. Beroukhim, Rameen Stefansson, Ingunn Mills, Gordon B. Krakstad, Camilla Salvesen, Helga B. TI Molecular profiling of endometrial carcinoma precursor, primary and metastatic lesions suggests different targets for treatment in obese compared to non-obese patients SO ONCOTARGET LA English DT Article DE endometrial carcinoma; endometrial hyperplasia; metastasis; body mass index; PI3Kinase ID GYNECOLOGIC-ONCOLOGY-GROUP; PTEN EXPRESSION; ATYPICAL HYPERPLASIA; PIK3CA MUTATIONS; HIGH-FREQUENCY; CANCER; GENE; WOMEN; RISK; AMPLIFICATION AB Obesity is linked to increased incidence of endometrioid endometrial cancer (EEC) and complex atypical hyperplasia (CAH). We here explore pattern and sequence of molecular alterations characterizing endometrial carcinogenesis in general and related to body mass index (BMI), to improve diagnostic stratification and treatment strategies. We performed molecular characterization of 729 prospectively collected EEC and CAH. Candidate biomarkers were identified in frozen samples by whole-exome and Sanger sequencing, oligonucleotide gene expression and Reverse Phase Protein Arrays (investigation cohort) and further explored in formalin fixed tissues by immunohistochemistry and Fluorescent in Situ Hybridization (validation cohort). We here demonstrate that PIK3CA mutations, PTEN loss, PI3K and KRAS activation are early events in endometrial carcinogenesis. Molecular changes related to KRAS activation and inflammation are more common in obese CAH patients, suggesting different prevention and systemic treatment strategies in obese and non-obese patients. We also found that oncoprotein Stathmin might improve preoperative diagnostic distinction between premalignant and malignant endometrial lesions. C1 [Berg, Anna; Hoivik, Erling A.; Mjos, Siv; Holst, Frederik; Werner, Henrica M. J.; Tangen, Ingvild L.; Kusonmano, Kanthida; Trovik, Jone; Halle, Mari K.; Oyan, Anne M.; Kalland, Karl-Henning; Krakstad, Camilla; Salvesen, Helga B.] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, N-5020 Bergen, Norway. [Berg, Anna; Hoivik, Erling A.; Mjos, Siv; Holst, Frederik; Werner, Henrica M. J.; Tangen, Ingvild L.; Kusonmano, Kanthida; Trovik, Jone; Halle, Mari K.; Krakstad, Camilla; Salvesen, Helga B.] Haukeland Hosp, Dept Gynecol & Obstet, Bergen, Norway. [Kusonmano, Kanthida] Univ Bergen, Computat Biol Unit, N-5020 Bergen, Norway. [Wik, Elisabeth; Stefansson, Ingunn] Haukeland Hosp, Dept Pathol, Bergen, Norway. [Wik, Elisabeth; Stefansson, Ingunn] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Med, N-5020 Bergen, Norway. [Oyan, Anne M.; Kalland, Karl-Henning] Haukeland Hosp, Dept Microbiol, Bergen, Norway. [Taylor-Weiner, Amaro; Gibson, William J.; Cherniack, Andrew D.; Beroukhim, Rameen] Broad Inst Harvard & MIT, Cambridge, MA USA. [Taylor-Weiner, Amaro; Gibson, William J.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Taylor-Weiner, Amaro; Gibson, William J.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Taylor-Weiner, Amaro; Gibson, William J.; Beroukhim, Rameen] Harvard Univ, Sch Med, Boston, MA USA. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. RP Salvesen, HB (reprint author), Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, N-5020 Bergen, Norway. EM Helga.salvesen@k2.uib.no RI Kalland, Karl-Henning/B-9445-2017; salvesen, Helga/C-1187-2017 OI Kalland, Karl-Henning/0000-0003-4486-2334; salvesen, Helga/0000-0002-4438-8831 FU Helse Vest; University of Bergen; Norwegian Cancer Society; Research Council of Norway; Bergen Medisinske Forskningsstiftelse; MD Anderson Cancer Center Support Grant (CCSG) from the National Cancer Institute [CA016672]; [P50 CA098258] FX HBS was supported by Helse Vest, the University of Bergen, the Norwegian Cancer Society (Harald Andersen Legat), and the Research Council of Norway, KC by Bergen Medisinske Forskningsstiftelse, GBM by P50 CA098258. RPPA analysis was supported by MD Anderson Cancer Center Support Grant (CCSG) CA016672 from the National Cancer Institute. NR 72 TC 13 Z9 13 U1 0 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 20 PY 2015 VL 6 IS 2 BP 1327 EP 1339 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CF4AE UT WOS:000352489800058 PM 25415225 ER PT J AU Stearns, V Chapman, JAW Ma, CX Ellis, MJ Ingle, JN Pritchard, KI Budd, GT Rabaglio, M Sledge, GW Le Maitre, A Kundapur, J Liedke, PER Shepherd, LE Goss, PE AF Stearns, Vered Chapman, Judith-Anne W. Ma, Cynthia X. Ellis, Matthew J. Ingle, James N. Pritchard, Kathleen I. Budd, G. Thomas Rabaglio, Manuela Sledge, George W. Le Maitre, Aurelie Kundapur, Jessica Liedke, Pedro E. R. Shepherd, Lois E. Goss, Paul E. TI Treatment-Associated Musculoskeletal and Vasomotor Symptoms and Relapse-Free Survival in the NCIC CTG MA.27 Adjuvant Breast Cancer Aromatase Inhibitor Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVERSE EVENTS; POSTMENOPAUSAL WOMEN; RISK; DISCONTINUATION; MANAGEMENT; EXEMESTANE; THERAPY AB Purpose Treatment-emergent symptoms with adjuvant tamoxifen and aromatase inhibitors (AIs) have been associated with superior recurrence-free survival (RFS). We hypothesized that MA. 27 anastrozoleor exemestane-treated patients with new or worsening vasomotor and/or joint symptoms would have improved RFS. Patients and Methods MA. 27 randomly assigned 7,576 postmenopausal women with breast cancer to 5 years of anastrozole or exemestane. Patient-reported symptoms were collected using the Common Terminology Criteria for Adverse Events version 3.0 at protocol-specified baseline and 6-and 12-month clinical visits. Symptoms were considered present with either vasomotor and/or joint complaints. Associations between symptoms and baseline patient characteristics were examined with chi(2) and Fisher's exact tests. Subsequent effects of new or worsening symptoms on RFS were examined with landmark analyses and stratified univariable and multivariable Cox models. We examined the effects of 3-month symptoms arising from unplanned clinic visits as a result of severe toxicity. Results Patients were assessable if eligible for the MA. 27 trial, received some trial therapy, and had no disease recurrence at the end of a symptom assessment period; 96% of patients (n = 7,306 patients) were included at 6 months, and 96% (n = 7,246) were included at 12 months. Thirty-four percent of patients had baseline symptoms. For patients without baseline symptoms, 25% and 52% had new symptoms by 6 and 12 months, respectively. Neither treatment-emergent nor baseline symptoms significantly impacted RFS (P >.10) in patients with or without baseline symptoms. Conclusion In MA. 27, anastrozole or exemestane treatment-emergent symptoms were not associated with improved RFS. Women should be supported through treatment and encouraged to remain on their AI regardless of their symptoms. (C) 2014 by American Society of Clinical Oncology C1 [Stearns, Vered] Kimmel Canc Ctr, Baltimore, MD USA. [Chapman, Judith-Anne W.; Le Maitre, Aurelie; Kundapur, Jessica; Shepherd, Lois E.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON K7L 3N6, Canada. [Pritchard, Kathleen I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Pritchard, Kathleen I.] Univ Toronto, Toronto, ON, Canada. [Ma, Cynthia X.] Washington Univ, Siteman Canc Ctr, St Louis, MO USA. [Ellis, Matthew J.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Ingle, James N.] Mayo Clin, Rochester, MN USA. [Budd, G. Thomas] Cleveland Clin, Cleveland, OH 44106 USA. [Sledge, George W.] Stanford Univ, San Francisco, CA USA. [Liedke, Pedro E. R.; Goss, Paul E.] Harvard Univ, Cambridge, MA 02138 USA. [Goss, Paul E.] Massachusetts Gen Hosp, Avon Int Breast Canc Res Program, Boston, MA 02114 USA. [Rabaglio, Manuela] Inselspital Univ Hosp, Bern, Switzerland. [Rabaglio, Manuela] Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. [Liedke, Pedro E. R.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Liedke, Pedro E. R.] Inst Canc Mae Deus, Oncol, Porto Alegre, RS, Brazil. RP Goss, PE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Lawrence House,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org FU NCI NIH HHS [U10 CA180888, P30 CA015083, U10 CA180833] NR 20 TC 10 Z9 10 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 BP 265 EP U163 DI 10.1200/JCO.2014.57.6926 PG 13 WC Oncology SC Oncology GA CF3BC UT WOS:000352421400011 PM 25512454 ER PT J AU Shulman, LN Berry, DA Cirrincione, CT Hudis, CA Winer, EP AF Shulman, Lawrence N. Berry, Donald A. Cirrincione, Constance T. Hudis, Clifford A. Winer, Eric P. TI Reply to V. Amoroso et al SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID POSITIVE BREAST-CANCER; ADJUVANT THERAPY C1 [Shulman, Lawrence N.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cirrincione, Constance T.] Duke Univ, Durham, NC USA. [Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Shulman, LN (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 BP 291 EP 291 DI 10.1200/JCO.2014.59.1875 PG 1 WC Oncology SC Oncology GA CF3BC UT WOS:000352421400019 PM 25512457 ER PT J AU Katz, IT Leister, E Kacanek, D Hughes, MD Bardeguez, A Livingston, E Stek, A Shapiro, DE Tuomala, R AF Katz, Ingrid T. Leister, Erin Kacanek, Deborah Hughes, Michael D. Bardeguez, Arlene Livingston, Elizabeth Stek, Alice Shapiro, David E. Tuomala, Ruth TI Factors Associated With Lack of Viral Suppression at Delivery Among Highly Active Antiretroviral Therapy-Naive Women With HIV A Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; EXPOSED UNINFECTED INFANTS; INFECTED PREGNANT-WOMEN; TO-CHILD TRANSMISSION; HIV-1-INFECTED WOMEN; UNITED-STATES; RISK-FACTORS; PERINATAL TRANSMISSION; HEALTH LITERACY; LOAD AB Background: A high delivery maternal plasma HIV-1 RNA level (viral load [VL]) is a risk factor for mother-to-child transmission and poor maternal health. Objective: To identify factors associated with detectable VL at delivery despite initiation of highly active antiretroviral therapy (HAART) during pregnancy. Design: Multicenter observational study. (ClinicalTrial.gov: NCT00028145) Setting: 67 U.S. AIDS clinical research sites. Patients: Pregnant women with HIV who initiated HAART during pregnancy. Measurements: Descriptive summaries and associations among sociodemographic, HIV disease, and treatment characteristics; pregnancy-related risk factors; and detectable VL (>400 copies/mL) at delivery. Results: Between 2002 and 2011, 671 women met inclusion criteria and 13.1% had detectable VL at delivery. Factors associated with detectable VL included multiparity (16.4% vs. 8.0% nulliparity; P = 0.002), black ethnicity (17.6% vs. 6.6% Hispanic and 6.6% white; P < 0.001), 11th grade education or less (17.6% vs. 12.1% had a high school diploma; P = 0.013), initiation of HAART in the third trimester (23.9% vs. 12.3% and 8.6% in the second and trimesters, respectively; P = 0.003), having an HIV diagnosis before the current pregnancy (16.1% vs. 11.0% during the current pregnancy; P = 0.051), and having the first prenatal visit in the third trimester (33.3% vs. 14.3% and 10.5% in the second and third trimesters, respectively; P = 0.002). Women who had treatment interruptions or reported poor medication adherence were more likely to have detectable VL at delivery. Limitation: Data on many covariates were incomplete because women entered the study at varying times during pregnancy. Conclusion: A total of 13.1% of women who initiated HAART during pregnancy had detectable VL at delivery. The timing of HAART initiation and prenatal care, along with medication adherence during pregnancy, were associated with detectable VL at delivery. Social factors, including ethnicity and education, may help identify women who could benefit from focused efforts to promote early HAART initiation and adherence. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brigham & Womens Hosp,Ctr Global Hlth, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Duke Univ, Sch Med, Durham, NC USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Katz, IT (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM ikatz2@partners.org FU U.S. Department of Health and Human Services FX U.S. Department of Health and Human Services. NR 48 TC 9 Z9 9 U1 1 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 20 PY 2015 VL 162 IS 2 BP 90 EP + DI 10.7326/M13-2005 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA CC1NB UT WOS:000350106600015 PM 25599347 ER PT J AU Ghatalia, P Je, Y Kaymakcalan, MD Sonpavde, G Choueiri, TK AF Ghatalia, P. Je, Y. Kaymakcalan, M. D. Sonpavde, G. Choueiri, T. K. TI QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors SO BRITISH JOURNAL OF CANCER LA English DT Article DE vascular endothelial growth factor receptor; tyrosine kinase inhibitors; approved; QTc interval prolongation; meta-analysis; cardiac toxicity ID RENAL-CELL CARCINOMA; PHASE-III TRIAL; VANDETANIB PLUS DOCETAXEL; DOUBLE-BLIND; LUNG-CANCER; CLINICAL-TRIALS; TREATMENT PATTERNS; CARDIOVASCULAR SAFETY; THYROID-CANCER; BREAST-CANCER AB Background: Multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are known to cause cardiac toxicity, but the relative risk (RR) of QTc interval prolongation and serious arrhythmias associated with them are not reported. Methods: We conducted a trial-level meta-analysis of randomised phase II and III trials comparing arms with and without a US Food and Drug Administration-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, axitinib, vandetanib, cabozantinib, ponatinib and regorafenib). A total of 6548 patients from 18 trials were selected. Statistical analyses were conducted to calculate the summary incidence, RR and 95% CIs. Results: The RR for all-grade and high-grade QTc prolongation for the TKI vs no TKI arms was 8.66 (95% CI 4.92-15.2, P < 0.001) and 2.69 (95% CI 1.33-5.44, P = 0.006), respectively, with most of the events being asymptomatic QTc prolongation. Respectively, 4.4% and 0.83% of patients exposed to VEGFR TKI had all-grade and high-grade QTc prolongation. On subgroup analysis, only sunitinib and vandetanib were associated with a statistically significant risk of QTc prolongation, with higher doses of vandetanib associated with a greater risk. The rate of serious arrhythmias including torsades de pointes did not seem to be higher with high-grade QTc prolongation. The risk of QTc prolongation was independent of the duration of therapy. Conclusions: In the largest study to date, we show that VEGFR TKI can be associated with QTc prolongation. Although most cases were of low clinical significance, it is unclear whether the same applies to patients treated off clinical trials. C1 [Ghatalia, P.] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL USA. [Je, Y.] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea. [Kaymakcalan, M. D.; Choueiri, T. K.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Kaymakcalan, M. D.; Choueiri, T. K.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Sonpavde, G.] UAB Med Ctr Birmingham, Sect Med Oncol, Dept Internal Med, Birmingham, AL USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM toni_choueiri@dfci.harvard.edu NR 51 TC 13 Z9 14 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 20 PY 2015 VL 112 IS 2 BP 296 EP 305 DI 10.1038/bjc.2014.564 PG 10 WC Oncology SC Oncology GA AZ5SY UT WOS:000348281100012 PM 25349964 ER PT J AU Norden, AD Ligon, KL Hammond, SN Muzikansky, A Reardon, DA Kaley, TJ Batchelor, TT Plotkin, SR Raizer, JJ Wong, ET Drappatz, J Lesser, GJ Haidar, S Beroukhim, R Lee, EQ Doherty, L Lafrankie, D Gaffey, SC Gerard, M Smith, KH McCluskey, C Phuphanich, S Wen, PY AF Norden, Andrew D. Ligon, Keith L. Hammond, Samantha N. Muzikansky, Alona Reardon, David A. Kaley, Thomas J. Batchelor, Tracy T. Plotkin, Scott R. Raizer, Jeffrey J. Wong, Eric T. Drappatz, Jan Lesser, Glenn J. Haidar, Sam Beroukhim, Rameen Lee, Eudocia Q. Doherty, Lisa Lafrankie, Debra Gaffey, Sarah C. Gerard, Mary Smith, Katrina H. McCluskey, Christine Phuphanich, Surasak Wen, Patrick Y. TI Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma SO NEUROLOGY LA English DT Article ID SOMATOSTATIN ANALOG; IN-VITRO; THERAPY; OCTREOTIDE; MUTATIONS; MECHANISM; SST(2A); AKT1; SMO AB Objective: A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective. Methods: Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6). Patients were stratified by histology (atypical [World Health Organization grade 2] and malignant [grade 3] meningiomas in cohort A and benign [grade 3] in cohort B). Results: Eighteen patients were accrued in cohort A and 16 in cohort B. Cohort A had median age 59 years, median Karnofsky performance status 80, 17 (94%) had previous radiation therapy, and 11 (61%) showed high octreotide uptake. Cohort B had median age 52 years, median Karnofsky performance status 90, 11 (69%) had previous radiation therapy, and 12 (75%) showed high octreotide uptake. There were no radiographic responses to pasireotide LAR therapy in either cohort. Twelve patients (67%) in cohort A and 13 (81%) in cohort B achieved stable disease. In cohort A, PFS6 was 17% and median PFS 15 weeks (95% confidence interval: 8-20). In cohort B, PFS6 was 50% and median PFS 26 weeks (12-43). Treatment was well tolerated. Octreotide uptake and insulin-like growth factor-1 levels did not predict outcome. Expression of somatostatin receptor 3 predicted favorable PFS and overall survival. Conclusions: Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation. Classification of evidence: This study provides Class IV evidence that in patients with recurrent or progressive meningioma, pasireotide LAR does not significantly increase the proportion of patients with PFS at 6 months. C1 [Norden, Andrew D.; Lee, Eudocia Q.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Canc Neurol, Boston, MA 02115 USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Beroukhim, Rameen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Norden, Andrew D.; Hammond, Samantha N.; Reardon, David A.; Beroukhim, Rameen; Lee, Eudocia Q.; Doherty, Lisa; Lafrankie, Debra; Gerard, Mary; Smith, Katrina H.; McCluskey, Christine; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Norden, Andrew D.; Ligon, Keith L.; Reardon, David A.; Batchelor, Tracy T.; Plotkin, Scott R.; Wong, Eric T.; Beroukhim, Rameen; Lee, Eudocia Q.; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. [Ligon, Keith L.; Haidar, Sam] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Kaley, Thomas J.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA. [Batchelor, Tracy T.; Plotkin, Scott R.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Raizer, Jeffrey J.] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA. [Wong, Eric T.] Beth Israel Deaconess Med Ctr, Brain Tumor Ctr, Boston, MA 02215 USA. [Drappatz, Jan] Univ Pittsburgh, Med Ctr, Adult Neurooncol Program, Pittsburgh, PA USA. [Lesser, Glenn J.] Wake Forest Univ, Ctr Comprehens Canc, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Phuphanich, Surasak] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA. [Phuphanich, Surasak] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, Div Canc Neurol, 75 Francis St, Boston, MA 02115 USA. EM pwen@partners.org OI Kaley, Thomas/0000-0002-2540-8518 FU Novartis FX This study was supported by Novartis. NR 24 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 20 PY 2015 VL 84 IS 3 BP 280 EP 286 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CA1XQ UT WOS:000348702600014 PM 25527270 ER PT J AU Arora, P Song, YN Dusek, J Plotnikoff, G Sabatine, MS Cheng, S Valcour, A Swales, H Taylor, B Carney, E Guanaga, D Young, JR Karol, C Torre, M Azzahir, A Strachan, SM O'Neill, DC Wolf, M Harrell, F Newton-Cheh, C Wang, TJ AF Arora, Pankaj Song, Yanna Dusek, Jeffery Plotnikoff, Gregory Sabatine, Marc S. Cheng, Susan Valcour, Andre Swales, Heather Taylor, Beth Carney, Erin Guanaga, Derek Young, Joseph R. Karol, Courtney Torre, Michael Azzahir, Atum Strachan, Semerit M. O'Neill, Dillon C. Wolf, Myles Harrell, Frank Newton-Cheh, Christopher Wang, Thomas J. TI Vitamin D Therapy in Individuals With Prehypertension or Hypertension The DAYLIGHT Trial SO CIRCULATION LA English DT Article DE blood pressure; dietary supplements; hypertension; vitamin D deficiency ID RANDOMIZED CONTROLLED-TRIAL; D-BINDING PROTEIN; BLOOD-PRESSURE; D SUPPLEMENTATION; CARDIOVASCULAR-DISEASE; PARATHYROID-HORMONE; D DEFICIENCY; RISK; RECOMMENDATIONS; ASSOCIATION AB Background-A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension. This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure, but data from prospective, randomized trials are limited. Methods and Results-A double-blind, randomized, controlled trial was conducted at 4 sites in the United States. We enrolled 534 individuals 18 to 50 years of age with low vitamin D status (25-hydroxyvitamin D levels <= 25 ng/mL) and systolic blood pressure of 120 to 159 mm Hg. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D 3 for 6 months. The primary end point was change in mean 24-hour systolic blood pressure. Secondary end points included change in ambulatory diastolic blood pressure and clinic systolic and diastolic blood pressures. The median age was 38 years, and 62% of participants were men. Forty-six percent of participants were white, and 48% were black. The median 25-hydroxyvitamin D level at baseline was 15.3 ng/mL. Four-hundred fifty-ive participants (85%) had at least 1 follow-up blood pressure measurement; 383 participants (72%) completed the full 6-month study. At the end of the study, there was no significant difference in the primary end point (change in mean 24-hour systolic blood pressure, -0.8 versus -1.6 mm Hg in the high-dose and low-dose arms; P=0.71) or in any of the secondary end points. Furthermore, there was no evidence of association between change in 25-hydroxyvitamin D and change in 24-hour systolic blood pressure at 6 months (Spearman correlation coefficient, -0.05, P=0.34). Results were consistent across prespecified subgroups. Conclusions-Vitamin D supplementation did not reduce blood pressure in individuals with prehypertension or stage I hypertension and vitamin D deficiency. Our findings suggest that the association between vitamin D status and elevated blood pressure noted in observational studies is not causal. C1 [Arora, Pankaj] Univ Alabama Birmingham, Div Cardiol, Dept Med, Birmingham, AL USA. [Song, Yanna; Harrell, Frank] Vanderbilt Univ, Dept Biostat, Nashville, TN 37232 USA. [O'Neill, Dillon C.; Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Dept Med, Nashville, TN 37232 USA. [Dusek, Jeffery; Plotnikoff, Gregory] Abbott NW Hosp, Integrat Hlth Res Ctr, Minneapolis, MN 55407 USA. [Sabatine, Marc S.; Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02115 USA. [Valcour, Andre] LabCorp, Esoterix Clin Lab Serv, Res Triangle Pk, NC USA. [Swales, Heather; Taylor, Beth] Hartford Hosp, Div Cardiol, Dept Med, Hartford, CT 06115 USA. [Carney, Erin; Guanaga, Derek; Young, Joseph R.; Karol, Courtney; Torre, Michael; Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Azzahir, Atum; Strachan, Semerit M.] Cultural Wellness Ctr, Div Cardiol, Minneapolis, MN USA. [Wolf, Myles] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Nephrol, Chicago, IL 60611 USA. RP Wang, TJ (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, 2220 Pierce Ave,383 PRB, Nashville, TN 37232 USA. EM thomas.j.wang@vanderbilt.edu OI Arora, Pankaj/0000-0003-2420-3550 FU DiaSorin Inc. FX The study was funded by an investigator-initiated grant from DiaSorin Inc. Additional assay support was provided by LabCorp Inc. DiaSorin Inc was not involved in the design or conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation of the manuscript for publication. NR 28 TC 27 Z9 29 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 20 PY 2015 VL 131 IS 3 BP 254 EP + DI 10.1161/CIRCULATIONAHA.114.011732 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AZ3KT UT WOS:000348126800010 PM 25359163 ER PT J AU Delling, FN Rong, J Larson, MG Lehman, B Osypiuk, E Stantchev, P Slaugenhaupt, SA Benjamin, EJ Levine, RA Vasan, RS AF Delling, Francesca N. Rong, Jian Larson, Martin G. Lehman, Birgitta Osypiuk, Ewa Stantchev, Plamen Slaugenhaupt, Susan A. Benjamin, Emelia J. Levine, Robert A. Vasan, Ramachandran S. TI Familial Clustering of Mitral Valve Prolapse in the Community SO CIRCULATION LA English DT Article DE echocardiography; epidemiology; genetics; mitral valve prolapse ID LATE SYSTOLIC MURMUR; MIDSYSTOLIC CLICK; NATURAL-HISTORY; REGURGITATION; HEART; DIAGNOSIS; LEAFLET; LOCUS; DETERMINANTS; INHERITANCE AB Background-Knowledge of mitral valve prolapse (MVP) inheritance is based on pedigree observation and M-mode echocardiography. The extent of familial clustering of MVP among unselected individuals in the community using current, more specific echocardiographic criteria is unknown. In addition, the importance of nondiagnostic MVP morphologies (NDMs; first described in large pedigrees) has not been investigated in the general population. We hypothesized that parental MVP and NDMs increase the risk of offspring MVP. Methods and Results-Study participants were 3679 Generation 3 individuals with available parental data in the Offspring or the New Offspring Spouse cohorts. MVP and NDMs were distinguished by leaflet displacement >2 versus <= 2 mm beyond the mitral annulus, respectively. We compared MVP prevalence in Generation 3 participants with at least 1 parent with MVP (n=186) with that in individuals without parental MVP (n=3493). Among 3679 participants (53% women; mean age, 40 +/- 9 years), 49 (1%) had MVP. Parental MVP was associated with a higher prevalence of MVP in Generation 3 participants (10 of 186, 5.4%) compared with no parental MVP (39 of 3493, 1.1%; adjusted odds ratio, 4.51; 95% confidence interval, 2.13-9.54; P<0.0001). When parental NDMs were examined alone, the prevalence of Generation 3 MVP remained higher (12 of 484, 2.5%) compared with those without parental MVP or NDMs (27 of 3009, 0.9%; adjusted odds ratio, 2.52; 95% confidence interval, 1.25-5.10; P=0.01). Conclusions-Parental MVP and NDMs are associated with increased prevalence of offspring MVP, highlighting the genetic substrate of MVP and the potential clinical significance of NDMs in the community. C1 [Delling, Francesca N.; Rong, Jian; Larson, Martin G.; Lehman, Birgitta; Osypiuk, Ewa; Stantchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Framingham, MA USA. [Delling, Francesca N.; Rong, Jian; Larson, Martin G.; Lehman, Birgitta; Osypiuk, Ewa; Stantchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Delling, Francesca N.] Harvard Univ, Sch Med, Dept Med, Cardiovasc Div,Beth Israel Deaconess Med Ctr, Boston, MA USA. [Rong, Jian] Boston Univ, Sch Med, Dept Med, Neurol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Sect Math & Stat, Boston, MA 02215 USA. [Slaugenhaupt, Susan A.] Univ Hartford, Ctr Human Genet Res, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Levine, Robert A.] Univ Hartford, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Dept Med,Med Sch, Boston, MA USA. RP Delling, FN (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Div, 330 Brookline Ave,E-SH-458, Boston, MA 02215 USA. EM fdelling@bidmc.harvard.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Founders Affiliate American Heart Association Clinical Research Program; National Heart, Lung, and Blood Institute FHS [N01-HC-25195]; [R01HL080124]; [RO1HL0107385]; [K23HL116652] FX This work was supported by the Founders Affiliate American Heart Association Clinical Research Program (Dr Delling), National Heart, Lung, and Blood Institute FHS contract No. N01-HC-25195, and research grants R01HL080124, RO1HL0107385 (Dr Vasan), and K23HL116652 (Dr Delling). NR 39 TC 7 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 20 PY 2015 VL 131 IS 3 BP 263 EP + DI 10.1161/CIRCULATIONAHA.114.012594 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AZ3KT UT WOS:000348126800011 PM 25361552 ER PT J AU Nelson, RW Beisang, D Tubo, NJ Dileepan, T Wiesner, DL Nielsen, K Wuthrich, M Klein, BS Kotov, DI Spanier, JA Fife, BT Moon, JJ Jenkins, MK AF Nelson, Ryan W. Beisang, Daniel Tubo, Noah J. Dileepan, Thamotharampillai Wiesner, Darin L. Nielsen, Kirsten Wuethrich, Marcel Klein, Bruce S. Kotov, Dmitri I. Spanier, Justin A. Fife, Brian T. Moon, James J. Jenkins, Marc K. TI T Cell Receptor Cross-Reactivity between Similar Foreign and Self Peptides Influences Naive Cell Population Size and Autoimmunity SO IMMUNITY LA English DT Article ID CLASS-II; PRECURSOR FREQUENCIES; REPERTOIRE DIVERSITY; RESPONSE MAGNITUDE; H-2(B) MICE; IN-VIVO; EPITOPE; INFECTION; COMPLEX; BINDING AB T cell receptor (TCR) cross-reactivity between major histocompatibility complex II (MHCII)-binding self and foreign peptides could influence the naive CD4(+) T cell repertoire and autoimmunity. We found that nonamer peptides that bind to the same MHCII molecule only need to share five amino acids to cross-react on the same TCR. This property was biologically relevant because systemic expression of a self peptide reduced the size of a naive cell population specific for a related foreign peptide by deletion of cells with cross-reactive TCRs. Reciprocally, an incompletely deleted naive T cell population specific for a tissue-restricted self peptide could be triggered by related microbial peptides to cause autoimmunity. Thus, TCR cross-reactivity between similar self and foreign peptides can reduce the size of certain foreign peptide-specific T cell populations and might allow T cell populations specific for tissue-restricted self peptides to cause autoimmunity after infection. C1 [Nelson, Ryan W.; Tubo, Noah J.; Dileepan, Thamotharampillai; Kotov, Dmitri I.; Spanier, Justin A.; Fife, Brian T.; Jenkins, Marc K.] Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA. [Nelson, Ryan W.; Beisang, Daniel; Tubo, Noah J.; Dileepan, Thamotharampillai; Wiesner, Darin L.; Nielsen, Kirsten; Kotov, Dmitri I.; Jenkins, Marc K.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. [Wuethrich, Marcel; Klein, Bruce S.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53706 USA. [Spanier, Justin A.; Fife, Brian T.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. [Moon, James J.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02129 USA. [Moon, James J.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Jenkins, MK (reprint author), Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA. EM jenki002@umn.edu OI Fife, Brian/0000-0001-9826-5637; Jenkins, Marc/0000-0001-8009-7655; Kotov, Dmitri/0000-0001-7843-1503 FU NIH [T32 GM008244, F30 DK093242, UL1 TR000114, R01 AI107020, R01 AI080275, R01 AI105816, R01 AI040996, R01 AI093553, P01 AI035296, R37 AI027998, R01 AI039614, R01 AI103760]; William F. Milton Fund FX We thank J. Walter and A. Quade for technical assistance, S. McSorley for the Aasf:I-Ab, RplF:I-Ab, and PmpG1:I-Ab tetramers, and all members of the Jenkins Laboratory for helpful discussions. Grants from the NIH (T32 GM008244 and F30 DK093242 to R.W.N., UL1 TR000114 to D. B., R01 AI107020 to J. J. M., R01 AI080275 to K.N., R01 AI105816 and R01 AI040996 to B. S. K., R01 AI093553 to M. W., P01 AI035296 to B. T. F., and R37 AI027998, R01 AI039614, P01 AI035296, and R01 AI103760 to M. K. J.) and the William F. Milton Fund (to J. J. M.) supported this work. NR 51 TC 36 Z9 36 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD JAN 20 PY 2015 VL 42 IS 1 BP 95 EP 107 DI 10.1016/j.immuni.2014.12.022 PG 13 WC Immunology SC Immunology GA AZ4NC UT WOS:000348197500014 PM 25601203 ER PT J AU Corrales-Medina, VF Alvarez, KN Weissfeld, LA Angus, DC Chirinos, JA Chang, CCH Newman, A Loehr, L Folsom, AR Elkind, MS Lyles, MF Kronmal, RA Yende, S AF Corrales-Medina, Vicente F. Alvarez, Karina N. Weissfeld, Lisa A. Angus, Derek C. Chirinos, Julio A. Chang, Chung-Chou H. Newman, Anne Loehr, Laura Folsom, Aaron R. Elkind, Mitchell S. Lyles, Mary F. Kronmal, Richard A. Yende, Sachin TI Association Between Hospitalization for Pneumonia and Subsequent Risk of Cardiovascular Disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE CORONARY SYNDROMES; HEART-DISEASE; INFLAMMATORY MARKERS; ATHEROSCLEROSIS RISK; OLDER AMERICANS; ACUTE INFECTION; SEVERE SEPSIS; SURVIVAL; MORTALITY; STROKE AB IMPORTANCE The risk of cardiovascular disease (CVD) after infection is poorly understood. OBJECTIVE To determine whether hospitalization for pneumonia is associated with an increased short-term and long-term risk of CVD. DESIGN, SETTINGS, AND PARTICIPANTS We examined 2 community-based cohorts: the Cardiovascular Health Study (CHS, n = 5888; enrollment age, >= 65 years; enrollment period, 1989-1994) and the Atherosclerosis Risk in Communities study (ARIC, n = 15 792; enrollment age, 45-64 years; enrollment period, 1987-1989). Participants were followed up through December 31, 2010. We matched each participant hospitalized with pneumonia to 2 controls. Pneumonia cases and controls were followed for occurrence of CVD over 10 years after matching. We estimated hazard ratios (HRs) for CVD at different time intervals, adjusting for demographics, CVD risk factors, subclinical CVD, comorbidities, and functional status. EXPOSURES Hospitalization for pneumonia. MAIN OUTCOMES AND MEASURES Incident CVD (myocardial infarction, stroke, and fatal coronary heart disease). RESULTS Of 591 pneumonia cases in CHS, 206 had CVD events over 10 years after pneumonia hospitalization. Compared with controls, CVD risk among pneumonia cases was highest during the first year after hospitalization and remained significantly higher than among controls through 10 years. In ARIC, of 680 pneumonia cases, 112 had CVD events over 10 years after hospitalization. After the second year, CVD risk among pneumonia cases was not significantly higher than among controls. [GRAPHICS] CONCLUSIONS AND RELEVANCE Hospitalization for pneumonia was associated with increased short-term and long-term risk of CVD, suggesting that pneumonia may be a risk factor for CVD. C1 [Corrales-Medina, Vicente F.] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Corrales-Medina, Vicente F.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Alvarez, Karina N.; Weissfeld, Lisa A.; Angus, Derek C.; Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, Clin Res Invest & Syst Modeling Acute Illness CRI, Pittsburgh, PA 15261 USA. [Weissfeld, Lisa A.; Chang, Chung-Chou H.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Chirinos, Julio A.] Univ Penn, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Philadelphia Vet Affairs Med Ctr, Div Cardiol, Philadelphia, PA USA. [Chang, Chung-Chou H.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. [Newman, Anne] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Loehr, Laura] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Elkind, Mitchell S.] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. [Elkind, Mitchell S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Lyles, Mary F.] Wake Forest Univ, Dept Med, Winston Salem, NC 27109 USA. [Kronmal, Richard A.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Yende, Sachin] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Yende, S (reprint author), Univ Pittsburgh, Dept Crit Care Med, Clin Res Invest & Syst Modeling Acute Illness CRI, 606D Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM angusdc@upmc.edu; yendes@upmc.edu RI Newman, Anne/C-6408-2013; Angus, Derek/E-9671-2012; OI Newman, Anne/0000-0002-0106-1150; Corrales-Medina, Vicente/0000-0002-9691-491X 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]; NHLBI [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; Department of Medicine of The Ottawa Hospital; Ottawa Hospital Research Institute in Ottawa, Ontario, Canada; National Institute of General Medical Sciences [K23GM083215, R01GM097471] FX The Cardiovascular Health Study (CHS) 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 grant AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS- NHLBI. org. The Atherosclerosis Risk in Communities study was supported by contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C from the NHLBI. This article is also supported by a Junior Investigator Award from the Department of Medicine of The Ottawa Hospital and the Ottawa Hospital Research Institute in Ottawa, Ontario, Canada (Dr Corrales- Medina) and by K23GM083215 and R01GM097471 from the National Institute of General Medical Sciences (Dr Yende). NR 41 TC 49 Z9 49 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 20 PY 2015 VL 313 IS 3 BP 264 EP 274 DI 10.1001/jama.2014.18229 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AZ3RS UT WOS:000348145000018 PM 25602997 ER PT J AU Malhotra, R Burke, MF Martyn, T Shakartzi, HR Thayer, TE O'Rourke, C Li, PC Derwall, M Spagnolli, E Kolodziej, SA Hoeft, K Mayeur, C Jiramongkolchai, P Kumar, R Buys, ES Yu, PB Bloch, KD Bloch, DB AF Malhotra, Rajeev Burke, Megan F. Martyn, Trejeeve Shakartzi, Hannah R. Thayer, Timothy E. O'Rourke, Caitlin Li, Pingcheng Derwall, Matthias Spagnolli, Ester Kolodziej, Starsha A. Hoeft, Konrad Mayeur, Claire Jiramongkolchai, Pawina Kumar, Ravindra Buys, Emmanuel S. Yu, Paul B. Bloch, Kenneth D. Bloch, Donald B. TI Inhibition of Bone Morphogenetic Protein Signal Transduction Prevents the Medial Vascular Calcification Associated with Matrix Gla Protein Deficiency SO PLOS ONE LA English DT Article ID CORONARY-ARTERY CALCIFICATION; SMOOTH-MUSCLE-CELLS; IN-VIVO; MOLECULAR-MECHANISMS; VULNERABLE PLAQUE; ENDOTHELIAL-CELLS; KEUTEL-SYNDROME; ATHEROSCLEROSIS; RUNX2; HYDROXYAPATITE AB Objective Matrix Gla protein (MGP) is reported to inhibit bone morphogenetic protein (BMP) signal transduction. MGP deficiency is associated with medial calcification of the arterial wall, in a process that involves both osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) and mesenchymal transition of endothelial cells (EndMT). In this study, we investigated the contribution of BMP signal transduction to the medial calcification that develops in MGP-deficient mice. Approach and Results MGP-deficient mice (MGP(-/-)) were treated with one of two BMP signaling inhibitors, LDN-193189 or ALK3-Fc, beginning one day after birth. Aortic calcification was assessed in 28-day-old mice by measuring the uptake of a fluorescent bisphosphonate probe and by staining tissue sections with Alizarin red. Aortic calcification was 80% less in MGP(-/-) mice treated with LDN-193189 or ALK3-Fc compared with vehicle-treated control animals (P < 0.001 for both). LDN-193189-treated MGP(-/-) mice survived longer than vehicle-treated MGP(-/-) mice. Levels of phosphorylated Smad1/5 and Id1 mRNA (markers of BMP signaling) did not differ in the aortas from MGP(-/-) and wild-type mice. Markers of EndMT and osteogenesis were increased in MGP(-/-) aortas, an effect that was prevented by LDN-193189. Calcification of isolated VSMCs was also inhibited by LDN-193189. Conclusions Inhibition of BMP signaling leads to reduced vascular calcification and improved survival in MGP(-/-) mice. The EndMT and osteogenic transdifferentiation associated with MGP deficiency is dependent upon BMP signaling. These results suggest that BMP signal transduction has critical roles in the development of vascular calcification in MGP-deficient mice. C1 [Malhotra, Rajeev; Burke, Megan F.; Thayer, Timothy E.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Malhotra, Rajeev; Burke, Megan F.; Thayer, Timothy E.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Boston, MA 02115 USA. [Martyn, Trejeeve; Shakartzi, Hannah R.; O'Rourke, Caitlin; Li, Pingcheng; Derwall, Matthias; Spagnolli, Ester; Kolodziej, Starsha A.; Hoeft, Konrad; Mayeur, Claire; Jiramongkolchai, Pawina; Buys, Emmanuel S.; Bloch, Kenneth D.; Bloch, Donald B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res,Dept Anesthesia Crit, Boston, MA 02115 USA. [Derwall, Matthias] Rhein Westfal TH Aachen, Uniklin Aachen, Dept Anesthesiol, Aachen, Germany. [Kumar, Ravindra] Acceleron Pharma Inc, Cambridge, MA USA. [Yu, Paul B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Bloch, Donald B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02115 USA. [Bloch, Donald B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02115 USA. RP Malhotra, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. EM rmalhotra@partners.org OI Yu, Paul/0000-0003-2145-4944; Malhotra, Rajeev/0000-0003-0120-4630 FU American Heart Association [11FTF7290032]; National Heart, Lung, and Blood Institute [K08HL111210]; Howard Hughes Medical Institute; Sarnoff Cardiovascular Research Foundation; START-Program of the Faculty of Medicine at RWTH Aachen (MD); Leducq Foundation; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR057374]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK082971] FX This work was supported by the American Heart Association Fellow-to-Faculty Award # 11FTF7290032 (RM); the National Heart, Lung, and Blood Institute (K08HL111210, RM); the Howard Hughes Medical Institute (TM and PJ); the Sarnoff Cardiovascular Research Foundation (MFB and TET); the START-Program of the Faculty of Medicine at RWTH Aachen (MD); the Leducq Foundation (Multidisciplinary Program to Elucidate the Role of Bone Morphogenetic Protein Signaling in the Pathogenesis of Pulmonary and Systemic Vascular Diseases, PBY and KDB); the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR057374, PBY); and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK082971, KDB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 9 Z9 9 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 20 PY 2015 VL 10 IS 1 AR e0117098 DI 10.1371/journal.pone.0117098 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ4OZ UT WOS:000348203500042 PM 25603410 ER PT J AU Walters, DL Raffel, OC Jang, IK AF Walters, Darren L. Raffel, O. Christopher Jang, Ik-Kyung TI Are the findings of optical coherence tomography sufficient for the evaluation of the safety and efficacy of the next generation of drug eluting stents? SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Editorial Material DE Optical coherence tomography; Coronary stent; Neointima ID COMPLETE NEOINTIMAL COVERAGE; INTRAVASCULAR ULTRASOUND; CLINICAL-APPLICATIONS; IMPLANTATION; THROMBOSIS; TERMINOLOGY; METHODOLOGY; APPOSITION; DOCUMENT; LIGHT C1 [Walters, Darren L.; Raffel, O. Christopher] Prince Charles Hosp, Brisbane, Qld 4032, Australia. [Walters, Darren L.; Raffel, O. Christopher] Univ Queensland, St Lucia, Qld, Australia. [Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jang, Ik-Kyung] Harvard Univ, Med Sch Boston, Cambridge, MA 02138 USA. RP Walters, DL (reprint author), Prince Charles Hosp, Dept Cardiol, Rode Rd, Brisbane, Qld 4032, Australia. EM darren.walters@health.qld.gov.au NR 25 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD JAN 20 PY 2015 VL 179 BP 127 EP 128 DI 10.1016/j.ijcard.2014.10.146 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW2AC UT WOS:000346089400043 PM 25464431 ER PT J AU Goto, T Gibo, K Hagiwara, Y Morita, H Brown, DFM Brown, CA Hasegawa, K AF Goto, Tadahiro Gibo, Koichiro Hagiwara, Yusuke Morita, Hiroshi Brown, David F. M. Brown, Calvin A., III Hasegawa, Kohei CA Japanese Emergency Med Network Inv TI Multiple failed intubation attempts are associated with decreased success rates on the first rescue intubation in the emergency department: a retrospective analysis of multicentre observational data SO SCANDINAVIAN JOURNAL OF TRAUMA RESUSCITATION & EMERGENCY MEDICINE LA English DT Article DE Intubation; Failed intubation; Rescue intubation; Success rate; Emergency department ID UNANTICIPATED DIFFICULT AIRWAY; RAPID-SEQUENCE INTUBATION; HOSPITAL CARDIAC-ARREST; TRACHEAL INTUBATION; ENDOTRACHEAL INTUBATION; MANAGEMENT; PATIENT; RECOMMENDATIONS; LARYNGOSCOPE; VENTILATION AB Background: Although the international guidelines emphasize early and systematic use of rescue intubation techniques, there is little evidence to support this notion. We aimed to test the hypothesis that preceding multiple failed intubation attempts are associated with a decreased success rate on the first rescue intubation in emergency departments (EDs). Methods: We analysed data from two multicentre prospective registries designed to characterize current ED airway management in Japan between April 2010 and June 2013. All patients who underwent a rescue intubation after a failed attempt or a series of failed attempts were included for the analysis. Multiple failed intubation attempts were defined as >= 2 consecutive failed intubation attempts before a rescue intubation. Primary outcome measure was success rate on the first rescue intubation attempt. Results: Of 6,273 consecutive patients, 1,151 underwent a rescue intubation. The success rate on the first rescue intubation attempt declined as the number of preceding failed intubation attempts increased (81% [95% CI, 79%-84%] after one failed attempt; 71% [95% CI, 66%-76%] after two failed attempts; 67% [95% CI, 55%-78%] after three or more failed attempts; P-trend < 0.001). In the multivariable analysis adjusting for age, sex, principal indication, change in methods, devices, and intubator specialty, and clustering of patients within EDs, success rate on the first rescue intubation after two failed attempts was significantly lower (OR, 0.56; 95% CI, 0.41-0.77) compared to that after one failed attempt. Similarly, success rate on the first rescue intubation attempt after three or more failed attempts was significantly lower (OR, 0.49; 95% CI, 0.25-0.94) compared to that after one failed attempt. Conclusion: Preceding multiple failed intubation attempts was independently associated with a decreased success rate on the first rescue intubation in the ED. C1 [Goto, Tadahiro; Morita, Hiroshi] Univ Fukui Hosp, Dept Emergency Med, Yoshida, Fukui 9101193, Japan. [Gibo, Koichiro] Okinawa Prefectural Chubu Hosp, Dept Emergency Med, Uruma, Okinawa 9042293, Japan. [Hagiwara, Yusuke] Tokyo Metropolitan Childrens Med Ctr, Dept Pediat Emergency & Crit Care Med, Div Pediat Emergency Med, Fuchu, Tokyo 1838561, Japan. [Brown, David F. M.; Hasegawa, Kohei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Brown, Calvin A., III] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. RP Goto, T (reprint author), Univ Fukui Hosp, Dept Emergency Med, 23-3 Shimoaiduki, Yoshida, Fukui 9101193, Japan. EM qq_gto@yahoo.co.jp FU St. Luke's Life Science Institute; Massachusetts General Hospital; Brigham and Women's Hospital (PI, Hasegawa) FX This study was supported by a grant from St. Luke's Life Science Institute and a grant from Massachusetts General Hospital and Brigham and Women's Hospital (PI, Hasegawa). The study sponsors have no involvement in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication NR 37 TC 5 Z9 5 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1757-7241 J9 SCAND J TRAUMA RESUS JI Scand. J. Trauma Resusc. Emerg. Med. PD JAN 16 PY 2015 VL 23 DI 10.1186/s13049-014-0085-8 PG 10 WC Emergency Medicine SC Emergency Medicine GA CD1OX UT WOS:000350845300001 PM 25700237 ER PT J AU Cheng, C Gao, NX Yu, CJ Wang, ZY Wang, J Hao, EH Wei, Y Mu, XL Tian, YL Ran, CZ Jiao, LJ AF Cheng, Chi Gao, Naixun Yu, Changjiang Wang, Zhaoyun Wang, Jun Hao, Erhong Wei, Yun Mu, Xiaolong Tian, Yanli Ran, Chongzhao Jiao, Lijuan TI Diversity-Oriented Facile Access to Highly Fluorescent Membrane-Permeable Benz[c,d]indole N-Heteroarene BF2 Dyes SO ORGANIC LETTERS LA English DT Article ID BORON DIFLUORIDE DYES; BODIPY DYES; BORATE COMPLEXES; GFP-CHROMOPHORE; FAR-RED; PROBES; ANALOGS; DESIGN; DERIVATIVES; STRATEGIES AB A diversity-oriented one-pot synthesis of a series of membrane-permeable BF2-rigidified benz[c,d]indole N-heteroarene BBN and BBC dyes has been achieved from the condensation of two commercial components (benz[c,d]indol-2-one and a set of N-heteroarene derivatives that can be selected from thousands of commercially available sources) and the subsequent in situ BF2 complexation reaction. These dyes enjoy a set of excellent photophysical properties including the large Stokes shift, high solution and solid-state fluorescence, and excellent photostabilities. C1 [Cheng, Chi; Gao, Naixun; Yu, Changjiang; Wang, Zhaoyun; Wang, Jun; Hao, Erhong; Wei, Yun; Mu, Xiaolong; Jiao, Lijuan] Anhui Normal Univ, Sch Chem & Mat Sci, Anhui Lab Mol Based Mat, Lab Funct Mol Solids,Minist Educ, Wuhu 241000, Anhui, Peoples R China. [Tian, Yanli; Ran, Chongzhao] Harvard Univ, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Mol Imaging Lab,Dept Radiol,Med Sch, Charlestown, MA 02129 USA. RP Ran, CZ (reprint author), Harvard Univ, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Mol Imaging Lab,Dept Radiol,Med Sch, Charlestown, MA 02129 USA. EM cran@nmr.mgh.harvard.edu; jiao421@mail.ahnu.edu.cn RI Jiao, Lijuan/C-2124-2015 FU National Nature Science Foundation of China [21072005, 21272007, 21372011]; Anhui Normal University [160-791310] FX This work is supported by the National Nature Science Foundation of China (Grant Nos. 21072005, 21272007, and 21372011) and the Research Culture Funds of Anhui Normal University (Grant No. 160-791310). NR 56 TC 21 Z9 21 U1 6 U2 64 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 EI 1523-7052 J9 ORG LETT JI Org. Lett. PD JAN 16 PY 2015 VL 17 IS 2 BP 278 EP 281 DI 10.1021/ol503379c PG 4 WC Chemistry, Organic SC Chemistry GA AZ6LR UT WOS:000348331800028 PM 25551331 ER PT J AU San Roman, AK Aronson, BE Krasinski, SD Shivdasani, RA Verzi, MP AF San Roman, Adrianna K. Aronson, Boaz E. Krasinski, Stephen D. Shivdasani, Ramesh A. Verzi, Michael P. TI Transcription Factors GATA4 and HNF4A Control Distinct Aspects of Intestinal Homeostasis in Conjunction with Transcription Factor CDX2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOOP-HELIX PROTEIN; GENE-EXPRESSION; INSULIN GENE; MOUSE COLON; ADULT; DIFFERENTIATION; EPITHELIUM; MAINTENANCE; PROMOTER; MICE AB Distinct groups of transcription factors (TFs) assemble at tissue- specific cis-regulatory sites, implying that different TF combinations may control different genes and cellular functions. Within such combinations, TFs that specify or maintain a lineage and are therefore considered master regulators may play a key role. Gene enhancers often attract these tissue-restricted TFs, as well as TFs that are expressed more broadly. However, the contributions of the individual TFs to combinatorial regulatory activity have not been examined critically in many cases in vivo. We address this question using a genetic approach in mice to inactivate the intestine-specifying and intestine-restricted factor CDX2 alone or in combination with its more broadly expressed partner factors, GATA4 and HNF4A. Compared with single mutants, each combination produced significantly greater defects and rapid lethality through distinct anomalies. Intestines lacking Gata4 and Cdx2 were deficient in crypt cell replication, whereas combined loss of Hnf4a and Cdx2 specifically impaired viability and maturation of villus enterocytes. Integrated analysis of TF binding and of transcripts affected in Hnf4a; Cdx2 compound-mutant intestines indicated that this TF pair controls genes required to construct the apical brush border and absorb nutrients, including dietary lipids. This study thus defines combinatorial TF activities, their specific requirements during tissue homeostasis, and modules of transcriptional targets in intestinal epithelial cells in vivo. C1 [San Roman, Adrianna K.; Shivdasani, Ramesh A.; Verzi, Michael P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [San Roman, Adrianna K.; Shivdasani, Ramesh A.; Verzi, Michael P.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [San Roman, Adrianna K.] Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Boston, MA 02115 USA. [Aronson, Boaz E.; Krasinski, Stephen D.] Boston Childrens Hosp, Div Pediat Gastroenterol & Nutr, Dept Med, Boston, MA 02115 USA. [Aronson, Boaz E.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands. [Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Verzi, Michael P.] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ramesh_shivdasani@dfci.harvard.edu; verzi@biology.rutgers.edu FU National Institutes of Health [R01DK08229, R01DK061382, F31CA180784, K01DK088868]; National Science Foundation; Human Genetics Institute of New Jersey; Nutricia Research Foundation; European Society for Pediatric Research; KWF Kankerbestrijding; Prins Bernhard Cultuurfonds; Specialized Program of Research Excellence in Gastrointestinal Cancer Award from the NCI, National Institutes of Health [P50CA127003] FX This work was supported, in whole or in part, by National Institutes of Health Grants R01DK08229 (to R. A. S.) and R01DK061382 (to S. D. K.) and Fellowships F31CA180784 (to A. K. S. R.) and K01DK088868 (to M. P. V.). This work was also supported by a National Science Foundation graduate research fellowship (to A. K. S. R.); the Human Genetics Institute of New Jersey (to M. P. V.); the Nutricia Research Foundation, the European Society for Pediatric Research, KWF Kankerbestrijding, and Prins Bernhard Cultuurfonds (to B. E. A.); and Specialized Program of Research Excellence in Gastrointestinal Cancer Award P50CA127003 from the NCI, National Institutes of Health. NR 45 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 16 PY 2015 VL 290 IS 3 BP 1850 EP 1860 DI 10.1074/jbc.M114.620211 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ2IB UT WOS:000348056400049 PM 25488664 ER PT J AU Nakazawa, H Yamada, M Tanaka, T Kramer, J Yu, YM Fischman, AJ Martyn, JAJ Tompkins, RG Kaneki, M AF Nakazawa, Harumasa Yamada, Marina Tanaka, Tomokazu Kramer, Joshua Yu, Yong-Ming Fischman, Alan J. Martyn, J. A. Jeevendra Tompkins, Ronald G. Kaneki, Masao TI Role of Protein Farnesylation in Burn-Induced Metabolic Derangements and Insulin Resistance in Mouse Skeletal Muscle SO PLOS ONE LA English DT Article ID NITRIC-OXIDE SYNTHASE; ENDOPLASMIC-RETICULUM STRESS; CRITICALLY-ILL PATIENTS; FARNESYLTRANSFERASE INHIBITOR; GLUCOSE-TOLERANCE; POTENTIAL ROLE; BASE DEFICIT; KINASE B; MICE; LACTATE AB Objective Metabolic derangements, including insulin resistance and hyperlactatemia, are a major complication of major trauma (e.g., burn injury) and affect the prognosis of burn patients. Protein farnesylation, a posttranslational lipid modification of cysteine residues, has been emerging as a potential component of inflammatory response in sepsis. However, farnesylation has not yet been studied in major trauma. To study a role of farnesylation in burn-induced metabolic aberration, we examined the effects of farnesyltransferase (FTase) inhibitor, FTI-277, on burn-induced insulin resistance and metabolic alterations in mouse skeletal muscle. Methods A full thickness burn (30% total body surface area) was produced under anesthesia in male C57BL/6 mice at 8 weeks of age. After the mice were treated with FTI-277 (5 mg/kg/day, IP) or vehicle for 3 days, muscle insulin signaling, metabolic alterations and inflammatory gene expression were evaluated. Results Burn increased FTase expression and farnesylated proteins in mouse muscle compared with sham-burn at 3 days after burn. Simultaneously, insulin-stimulated phosphorylation of insulin receptor (IR), insulin receptor substrate (IRS)-1, Akt and GSK-3 beta was decreased. Protein expression of PTP-1B (a negative regulator of IR-IRS-1 signaling), PTEN (a negative regulator of Akt-mediated signaling), protein degradation and lactate release by muscle, and plasma lactate levels were increased by burn. Burn-induced impaired insulin signaling and metabolic dysfunction were associated with increased inflammatory gene expression. These burn-induced alterations were reversed or ameliorated by FTI-277. Conclusions Our data demonstrate that burn increased FTase expression and protein farnesylation along with insulin resistance, metabolic alterations and inflammatory response in mouse skeletal muscle, all of which were prevented by FTI-277 treatment. These results indicate that increased protein farnesylation plays a pivotal role in burn-induced metabolic dysfunction and inflammatory response. Our study identifies FTase as a novel potential molecular target to reverse or ameliorate metabolic derangements in burn patients. C1 [Nakazawa, Harumasa; Yamada, Marina; Tanaka, Tomokazu; Martyn, J. A. Jeevendra; Kaneki, Masao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Yamada, Marina; Yu, Yong-Ming; Fischman, Alan J.; Martyn, J. A. Jeevendra; Kaneki, Masao] Shriners Hosp Children, Boston, MA USA. [Kramer, Joshua] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Yu, Yong-Ming; Tompkins, Ronald G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Kaneki, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. EM mkaneki@helix.mgh.harvard.edu FU Shriners Hospitals for Children [71000, 85800, 84203]; National Institutes of Health(NIGMS) [P50GM02700] FX This work was supported by a research grant to MK (71000, 85800) and a fellowship to MY (84203) from Shriners Hospitals for Children, and to RGT (P50GM02700) from National Institutes of Health(NIGMS). The funders had no role in study design, date collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 5 Z9 5 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 16 PY 2015 VL 10 IS 1 AR e0116633 DI 10.1371/journal.pone.0116633 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ4OS UT WOS:000348202900004 PM 25594415 ER PT J AU Flynn, RL Cox, KE Jeitany, M Wakimoto, H Bryll, AR Ganem, NJ Bersani, F Pineda, JR Suva, ML Benes, CH Haber, DA Boussin, FD Zou, L AF Flynn, Rachel Litman Cox, Kelli E. Jeitany, Maya Wakimoto, Hiroaki Bryll, Alysia R. Ganem, Neil J. Bersani, Francesca Pineda, Jose R. Suva, Mario L. Benes, Cyril H. Haber, Daniel A. Boussin, Francois D. Zou, Lee TI Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors SO SCIENCE LA English DT Article ID REPEAT-CONTAINING RNA; SINGLE-STRANDED-DNA; HOMOLOGOUS RECOMBINATION; CHROMOSOME ENDS; PROTEIN-KINASE; MUTATIONS; GLIOBLASTOMA; TUMORS; POLYMERASE; DISCOVERY AB Cancer cells rely on telomerase or the alternative lengthening of telomeres (ALT) pathway to overcome replicative mortality. ALT is mediated by recombination and is prevalent in a subset of human cancers, yet whether it can be exploited therapeutically remains unknown. Loss of the chromatin-remodeling protein ATRX associates with ALT in cancers. Here, we show that ATRX loss compromises cell-cycle regulation of the telomeric noncoding RNA TERRA and leads to persistent association of replication protein A (RPA) with telomeres after DNA replication, creating a recombinogenic nucleoprotein structure. Inhibition of the protein kinase ATR, a critical regulator of recombination recruited by RPA, disrupts ALT and triggers chromosome fragmentation and apoptosis in ALT cells. The cell death induced by ATR inhibitors is highly selective for cancer cells that rely on ALT, suggesting that such inhibitors may be useful for treatment of ALT-positive cancers. C1 [Flynn, Rachel Litman; Bersani, Francesca; Suva, Mario L.; Benes, Cyril H.; Haber, Daniel A.; Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Flynn, Rachel Litman; Cox, Kelli E.; Bryll, Alysia R.; Ganem, Neil J.] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Ctr Canc, Boston, MA 02118 USA. [Flynn, Rachel Litman; Cox, Kelli E.; Bryll, Alysia R.; Ganem, Neil J.] Boston Univ, Sch Med, Dept Med, Ctr Canc, Boston, MA 02118 USA. [Jeitany, Maya; Pineda, Jose R.; Boussin, Francois D.] CEA Fontenay Aux Roses, Inst Radiobiol Cellulaire & Mol, Lab Radiopathol, UMR 967, Fontenay Aux Roses, France. [Wakimoto, Hiroaki] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. [Wakimoto, Hiroaki] Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02115 USA. [Bersani, Francesca; Haber, Daniel A.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Charlestown, MA 02129 USA. [Suva, Mario L.; Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Flynn, RL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM rlflynn@bu.edu; zou.lee@mgh.harvard.edu RI Pineda, Jose/F-9710-2015 OI Pineda, Jose/0000-0002-0900-7466 FU Wellcome Trust [102696]; Irtelis CEA Ph.D. program; INCA "TetraTips" [PLBIO10-030]; NIH [CA166729, GM076388]; Karin Grunebaum Cancer Research Foundation; Foster Foundation FX We thank S. Artandi, W. Wright, H. Yu, M.P. Junier, and Q. Yang for reagents; A. Manning, A. Jimenez, D. Ramirez, and T. Kortulewski for technical assistance; and members of the Zou lab for helpful discussions. C.H.B. is supported by a grant from the Wellcome Trust (102696). M.J. has a fellowship from Irtelis CEA Ph.D. program. F.B. has a grant from INCA "TetraTips" (PLBIO10-030). R.L.F. is supported by the NIH K99/R00 Award (CA166729), the Karin Grunebaum Cancer Research Foundation, and the Foster Foundation. L.Z. is a Jim and Ann Orr Massachusetts General Hospital Research Scholar, a Senior Scholar of the Ellison Medical Foundation, and supported by the NIH grant GM076388. NR 33 TC 86 Z9 87 U1 8 U2 58 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 16 PY 2015 VL 347 IS 6219 BP 273 EP 277 DI 10.1126/science.1257216 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ0DA UT WOS:000347915300036 PM 25593184 ER PT J AU Penaloza-MacMaster, P Barber, DL Wherry, EJ Provine, NM Teigler, JE Parenteau, L Blackmore, S Borducchi, EN Larocca, RA Yates, KB Shen, H Haining, WN Sommerstein, R Pinschewer, DD Ahmed, R Barouch, DH AF Penaloza-MacMaster, Pablo Barber, Daniel L. Wherry, E. John Provine, Nicholas M. Teigler, Jeffrey E. Parenteau, Lily Blackmore, Stephen Borducchi, Erica N. Larocca, Rafael A. Yates, Kathleen B. Shen, Hao Haining, W. Nicholas Sommerstein, Rami Pinschewer, Daniel D. Ahmed, Rafi Barouch, Dan H. TI Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection SO SCIENCE LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; CHRONIC VIRAL-INFECTION; CD8-T-CELL MEMORY; CD4-T-CELL HELP; CD8(+); RESPONSES; PERSISTENCE; EPITOPE; IDENTIFICATION; ACTIVATION AB CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology. C1 [Penaloza-MacMaster, Pablo; Provine, Nicholas M.; Teigler, Jeffrey E.; Parenteau, Lily; Blackmore, Stephen; Borducchi, Erica N.; Larocca, Rafael A.; Barouch, Dan H.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Barber, Daniel L.] NIAID, Lab Parasit Dis, Bethesda, MD 20892 USA. [Wherry, E. John; Shen, Hao] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Wherry, E. John; Shen, Hao] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Yates, Kathleen B.; Haining, W. Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sommerstein, Rami; Pinschewer, Daniel D.] Univ Geneva, WHO Collaborating Ctr Vaccine Immunol, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland. [Pinschewer, Daniel D.] Univ Basel, Div Expt Virol, Dept Biomed Haus Peterspl, CH-4009 Basel, Switzerland. [Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Barouch, Dan H.] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. RP Barouch, DH (reprint author), Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. EM dbarouch@bidmc.harvard.edu OI Sommerstein, Rami/0000-0003-1011-6878 FU NIH [AI007245, AI07387, AI078526, AI096040, AI030048]; Bill and Melinda Gates Foundation [OPP1033091]; Swiss National Science Foundation [310030_149340/1]; European Research Council; Ragon Institute; NIAID Intramural Research Program FX We thank A. Wieland, M. Rasheed, A. Kamphorst, K. Araki, S. Crotty, B. Walker, C. Bricault, P. Abbink, and F. Ball for generous advice, assistance, and reagents. The data presented in this manuscript are tabulated in the main paper and the supplementary materials. Supported by NIH grants AI007245 and AI07387 (P.P.M.), AI078526 and AI096040 (D.H.B.), and AI030048 (R.A.); Bill and Melinda Gates Foundation grant OPP1033091 (D.H.B.); Swiss National Science Foundation grant 310030_149340/1 (D.D.P.); the European Research Council (D.D.P.) the Ragon Institute (D.H.B.); and the NIAID Intramural Research Program (D.L.B.). Gene expression data have been uploaded to GEO (accession no. GSE63825). The authors declare no financial conflicts of interest. NR 29 TC 13 Z9 13 U1 0 U2 16 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 16 PY 2015 VL 347 IS 6219 BP 278 EP 283 DI 10.1126/science.aaa2148 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ0DA UT WOS:000347915300037 PM 25593185 ER PT J AU Lei, XY Liu, CX Azadzoi, K Li, CL Lu, F Xiang, A Sun, JB Guo, YH Zhao, QC Yan, Z Yang, JH AF Lei, Xiaoying Liu, Chaoxu Azadzoi, Kazem Li, Cuiling Lu, Fan Xiang, An Sun, Jianbin Guo, Yanhai Zhao, Qingchuan Yan, Zhen Yang, Jinghua TI A novel IgM-H-Ficolin complement pathway to attack allogenic cancer cells in vitro SO SCIENTIFIC REPORTS LA English DT Article ID CIBACRON BLUE F3GA; MONOCLONAL-ANTIBODIES; TUMOR IMMUNOGENICITY; ADAPTIVE IMMUNITY; BINDING; INNATE; IMMUNOSURVEILLANCE; ACTIVATION; MOLECULE; NEUROBLASTOMA AB The pentameric serum IgMs are critical to immune defense and surveillance through cytotoxicity against microbes and nascent cancer cells. Ficolins, a group of oligomeric lectins with an overall structure similar to C1q and mannose-binding lectin (MBL) participate in microbe infection and apoptotic cell clearance by activating the complement lectin pathway or a primitive opsonophagocytosis. It remains unknown whether serum IgMs interplay with ficolins in cancer immunosurveillance. Here we report a natural cancer killing of different types of cancer cells by sera from a healthy human population mediated by a novel IgM-H-ficolin complement activation pathway. We demonstrate for the first time that H-ficolin bound to a subset of IgMs in positive human sera and IgM-H-ficolin deposited on cancer cells to activate complement attack in cancer cells. Our data suggest that the IgM-H-ficolin -mediated complement activation pathway may be another defensive strategy for human cancer immunosurveillance. C1 [Lei, Xiaoying; Xiang, An; Sun, Jianbin; Guo, Yanhai; Yan, Zhen] Fourth Mil Med Univ, Sch Pharm, Dept Pharmacogen, State Key Lab Canc Biol, Xian 710032, Peoples R China. [Liu, Chaoxu; Azadzoi, Kazem; Yang, Jinghua] Boston Univ, Dept Surg, VA Boston Healthcare Syst, Sch Med, Boston, MA 02130 USA. [Liu, Chaoxu; Azadzoi, Kazem; Yang, Jinghua] Boston Univ, Dept Urol, VA Boston Healthcare Syst, Sch Med, Boston, MA 02130 USA. [Li, Cuiling; Yang, Jinghua] Shandong Univ, Sch Med, Canc Res Ctr, Jinan 250000, Peoples R China. [Lu, Fan] Fourth Mil Med Univ, Dept Biochem & Mol Biol, State Key Lab Canc Biol, Xian 710032, Peoples R China. [Zhao, Qingchuan] Fourth Mil Med Univ, Xijing Hosp, Dept Gastroenterol, State Key Lab Canc Biol, Xian 710032, Peoples R China. RP Yang, JH (reprint author), Boston Univ, Dept Surg, VA Boston Healthcare Syst, Sch Med, Boston, MA 02130 USA. EM yanzhen@fmmu.edu.cn; jyang@bu.edu FU Susan G. Komen Foundation [BCTR0707230]; 985 program of Shandong University; National Natural Science Foundation of China [30901357, 81200323, 81272276]; National Key Basic Research Program [2010CB933902] FX This work was jointly supported by the Susan G. Komen Foundation for a Cure (No. BCTR0707230) and the 985 program of Shandong University to Dr. J.H.Y., the National Natural Science Foundation of China (No. 30901357; No. 81200323; No. 81272276) and the National Key Basic Research Program (No. 2010CB933902) to Dr. J.H.Y., Z.Y., X.Y.L. and C. X.L. This is the result of work partially supported with resources and the use of facilities at VA Boston Healthcare System. The authors thank Medjaden Bioscience company for English proofreading. NR 38 TC 4 Z9 4 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 16 PY 2015 VL 5 AR 7824 DI 10.1038/srep07824 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY9YN UT WOS:000347903800005 PM 25592840 ER PT J AU Dietz, KN Di Stefano, L Maher, RC Zhu, H Macdonald, ME Gusella, JF Walker, JA AF Dietz, Kevin N. Di Stefano, Luisa Maher, Robert C. Zhu, Hui Macdonald, Marcy E. Gusella, James F. Walker, James A. TI The Drosophila Huntington's disease gene ortholog dhtt influences chromatin regulation during development SO HUMAN MOLECULAR GENETICS LA English DT Article ID WILD-TYPE HUNTINGTIN; HISTONE METHYLTRANSFERASE ACTIVITY; POSITION-EFFECT VARIEGATION; TRANSCRIPTION FACTOR; NUCLEOSOME DYNAMICS; EMBRYONIC LETHALITY; CHROMOSOMAL-PROTEIN; REPRESSOR COMPLEX; DNA METHYLATION; POLYCOMB AB Huntington's disease is an autosomal dominant neurodegenerative disorder caused by a CAG expansion mutation in HTT, the gene encoding huntingtin. Evidence from both human genotype-phenotype relationships and mouse model systems suggests that the mutation acts by dysregulating some normal activity of huntingtin. Recent work in the mouse has revealed a role for huntingtin in epigenetic regulation during development. Here, we examine the role of the Drosophila huntingtin ortholog (dhtt) in chromatin regulation in the development of the fly. Although null dhtt mutants display no overt phenotype, we found that dhtt acts as a suppressor of position-effect variegation (PEV), suggesting that it influences chromatin organization. We demonstrate that dhtt affects heterochromatin spreading in a PEV model by modulating histone H3K9 methylation levels at the heterochromatin-euchromatin boundary. To gain mechanistic insights into how dhtt influences chromatin function, we conducted a candidate genetic screen using RNAi lines targeting known PEV modifier genes. We found that dhtt modifies phenotypes caused by knockdown of a number of key epigenetic regulators, including chromatin-associated proteins, histone demethylases (HDMs) and methyltransferases. Notably, dhtt strongly modifies phenotypes resulting from loss of the HDM dLsd1, in both the ovary and wing, and we demonstrate that dhtt appears to act as a facilitator of dLsd1 function in regulating global histone H3K4 methylation levels. These findings suggest that a fundamental aspect of huntingtin function in heterochromatin/euchromatin organization is evolutionarily conserved across phyla. C1 [Dietz, Kevin N.; Zhu, Hui; Macdonald, Marcy E.; Gusella, James F.; Walker, James A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Dietz, Kevin N.; Zhu, Hui; Macdonald, Marcy E.; Gusella, James F.; Walker, James A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Di Stefano, Luisa] Univ Toulouse, UMR 5088, Lab Biol Cellulaire & Mol Controle Proliferat, UMR 5088, F-31062 Toulouse, France. [Di Stefano, Luisa] CNRS, F-31062 Toulouse, France. [Maher, Robert C.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. RP Walker, JA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM jwalker@helix.mgh.harvard.edu FU Huntington's Disease Society of America [NS16367]; CHDI Foundation, Inc.; Fondation pour la Recherche Medicale (FRM) FX This work was supported by the Huntington's Disease Society of America (grant NS16367) and CHDI Foundation, Inc. LDS was funded by the Fondation pour la Recherche Medicale (FRM). NR 91 TC 4 Z9 4 U1 3 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 15 PY 2015 VL 24 IS 2 BP 330 EP 345 DI 10.1093/hmg/ddu446 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CC1WV UT WOS:000350137000003 PM 25168387 ER PT J AU Froehner, SC Reed, SM Anderson, KN Huang, PL Percival, JM AF Froehner, Stanley C. Reed, Sarah M. Anderson, Kendra N. Huang, Paul L. Percival, Justin M. TI Loss of nNOS inhibits compensatory muscle hypertrophy and exacerbates inflammation and eccentric contraction-induced damage in mdx mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID NITRIC-OXIDE SYNTHASE; DUCHENNE-MUSCULAR-DYSTROPHY; DEFICIENT SKELETAL-MUSCLE; S-NITROSYLATION; MOUSE MODEL; ALPHA-SYNTROPHIN; INDUCED INJURY; SARCOLEMMA; FATIGUE; MECHANISM AB Approaches targeting nitric oxide (NO) signaling show promise as therapies for Duchenne and Becker muscular dystrophies. However, the mechanisms by which NO benefits dystrophin-deficient muscle remain unclear, but may involve nNOS beta, a newly discovered enzymatic source of NO in skeletal muscle. Here we investigate the impact of dystrophin deficiency on nNOS beta and use mdx mice engineered to lack nNOS mu and nNOS beta to discern how the loss of nNOS impacts dystrophic skeletal muscle pathology. In mdx muscle, nNOS beta was mislocalized and its association with the Golgi complex was reduced. nNOS depletion from mdx mice prevented compensatory skeletal muscle cell hypertrophy, decreased myofiber central nucleation and increased focal macrophage cell infiltration, indicating exacerbated dystrophic muscle damage. Reductions in muscle integrity in nNOS-null mdx mice were accompanied by decreases in specific force and increased susceptibility to eccentric contraction-induced muscle damage compared with mdx controls. Unexpectedly, muscle fatigue was unaffected by nNOS depletion, revealing a novel latent compensatory mechanism for the loss of nNOS in mdx mice. Together with previous studies, these data suggest that localization of both nNOS mu and nNOS beta is disrupted by dystrophin deficiency. They also indicate that nNOS has a more complex role as a modifier of dystrophic pathology and broader therapeutic potential than previously recognized. Importantly, these findings also suggest nNOS beta as a new drug target and provide a new conceptual framework for understanding nNOS signaling and the benefits of NO therapies in dystrophinopathies. C1 [Froehner, Stanley C.; Reed, Sarah M.; Anderson, Kendra N.; Percival, Justin M.] Univ Washington, Sch Med, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Percival, Justin M.] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA. RP Percival, JM (reprint author), Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol R 189, POB 016189, Miami, FL 33101 USA. EM j.percival@med.miami.edu FU Muscular Dystrophy Association; NIAMS of the National Institutes of Health [69075, NS33145, AR056221]; American Physiological Society Undergraduate Summer Research Fellowship; Mary Gates Research Scholarship FX Research reported in this publication was supported by the Muscular Dystrophy Association and by NIAMS of the National Institutes of Health under award numbers 69075 (JMP), NS33145 and AR056221 (SCF). SMR was supported by an American Physiological Society Undergraduate Summer Research Fellowship and Mary Gates Research Scholarship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 65 TC 5 Z9 5 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 15 PY 2015 VL 24 IS 2 BP 492 EP 505 DI 10.1093/hmg/ddu469 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CC1WV UT WOS:000350137000016 PM 25214536 ER PT J AU Dotson, AL Wang, JM Saugstad, J Murphy, SJ Offner, H AF Dotson, Abby L. Wang, Jianming Saugstad, Julie Murphy, Stephanie J. Offner, Halina TI Splenectomy reduces infarct volume and neuroinflammation in male but not female mice in experimental stroke SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Experimental stroke; Sex difference; Immune response; Neuroinflammation; Infarct volume; Splenectomy ID REGULATORY T-CELLS; ACUTE ISCHEMIC-STROKE; NECROSIS-FACTOR-ALPHA; BRAIN-INJURY; CEREBRAL-ISCHEMIA; INFLAMMATION; SEX; EXPRESSION; PROTECTS; ESTROGEN AB The peripheral immune response contributes to neurodegeneration after stroke yet little is known about how this process differs between males and females. The current study demonstrates that splenectomy prior to experimental stroke eliminates sex differences in infarct volume and activated brain monocytes/microglia. In the periphery of both sexes, activated T cells correlate directly with stroke outcome while monocytes are reduced by splenectomy only in males. This study provides new information about the sex specific mechanisms of the peripheral immune response in neurodegeneration after stroke and demonstrates the need for representation of both sexes in basic and clinical stroke research. (C) 2014 Elsevier B.V. All rights reserved. C1 [Dotson, Abby L.; Offner, Halina] VA Med Ctr, Portland, OR USA. [Dotson, Abby L.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Wang, Jianming; Saugstad, Julie; Murphy, Stephanie J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIH [NS076013]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX The authors wish to thank Gail Kent for assistance with manuscript submission. This work was supported by NIH Grant # NS076013 and by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 37 TC 9 Z9 9 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 EI 1872-8421 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN 15 PY 2015 VL 278 BP 289 EP 298 DI 10.1016/j.jneuroim.2014.11.020 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CA9UC UT WOS:000349269300037 PM 25434281 ER PT J AU Kim, DH Martin, JT Elliott, DM Smith, LJ Mauck, RL AF Kim, Dong Hwa Martin, John T. Elliott, Dawn M. Smith, Lachlan J. Mauck, Robert L. TI Phenotypic stability, matrix elaboration and functional maturation of nucleus pulposus cells encapsulated in photocrosslinkable hyaluronic acid hydrogels SO ACTA BIOMATERIALIA LA English DT Article DE Intervertebral disc degeneration; Cell therapy; Three-dimensional culture; Mechanical properties; Tissue engineering ID INTERVERTEBRAL DISC CELLS; IN-VITRO; ARTICULAR-CARTILAGE; ENGINEERED CARTILAGE; REGENERATION; CHONDROCYTES; EXPRESSION; GENE; GELS; DIFFERENTIATION AB Degradation of the nucleus pulposus (NP) is an early hallmark of intervertebral disc degeneration. The capacity for endogenous regeneration in the NP is limited due to the low cellularity and poor nutrient and vascular supply. Towards restoring the NP, a number of biomaterials have been explored for cell delivery. These materials must support the NP cell phenotype while promoting the elaboration of an NP-like extracellular matrix in the shortest possible time. Our previous work with chondrocytes and mesenchymal stem cells demonstrated that hydrogels based on hyaluronic acid (HA) are effective at promoting matrix production and the development of functional material properties. However, this material has not been evaluated in the context of NP cells. Therefore, to test this material for NP regeneration, bovine NP cells were encapsulated in 1% w/vol HA hydrogels at either a low seeding density (20 x 10(6) cells ml(-1)) or a high seeding density (60 x 10(6) cells ml(-1)), and constructs were cultured over an 8 week period. These NP cell-laden HA hydrogels showed functional matrix accumulation, with increasing matrix content and mechanical properties with time in culture at both seeding densities. Furthermore, encapsulated cells showed NP-specific gene expression profiles that were significantly higher than expanded NP cells prior to encapsulation, suggesting a restoration of phenotype. Interestingly, these levels were higher at the lower seeding density compared to the higher seeding density. These findings support the use of HA-based hydrogels for NP tissue engineering and cellular therapies directed at restoration or replacement of the endogenous NP. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Kim, Dong Hwa; Martin, John T.; Smith, Lachlan J.; Mauck, Robert L.] Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. [Kim, Dong Hwa; Martin, John T.; Smith, Lachlan J.; Mauck, Robert L.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. [Martin, John T.; Mauck, Robert L.] Univ Penn, Dept Mech Engn & Appl Mech, Philadelphia, PA 19104 USA. [Elliott, Dawn M.] Univ Delaware, Dept Biomed Engn, Newark, DE 19716 USA. [Smith, Lachlan J.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. [Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. RP Mauck, RL (reprint author), Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, 36th St & Hamilton Walk,424 Stemmler Hall, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu FU Department of Defense [OR090090]; Department of Veterans Affairs [101 RX000211]; Penn Center for Musculoskeletal Disorders [P30 AR050950] FX This work was supported by the Department of Defense (Grant OR090090), the Department of Veterans Affairs (Grant 101 RX000211) and the Penn Center for Musculoskeletal Disorders (Grant P30 AR050950). NR 51 TC 8 Z9 9 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 EI 1878-7568 J9 ACTA BIOMATER JI Acta Biomater. PD JAN 15 PY 2015 VL 12 BP 21 EP 29 DI 10.1016/j.actbio.2014.10.030 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CA1QF UT WOS:000348686100003 PM 25448344 ER PT J AU Khera, AV Qamar, A Reilly, MP Dunbar, RL Rader, DJ AF Khera, Amit V. Qamar, Arman Reilly, Muredach P. Dunbar, Richard L. Rader, Daniel J. TI Effects of Niacin, Statin, and Fenofibrate on Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels in Patients With Dyslipidemia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; LDL CHOLESTEROL; PCSK9; HYPERCHOLESTEROLEMIA; ATORVASTATIN; TOLERABILITY; EFFICACY; PHASE-2; SAFETY; TRIAL AB Recent trials demonstrated substantial improvement in lipid parameters with inhibition of proprotein convertase subtilisin-like/kexin type 9 (PCSK9). Although statins and fibrates have been reported to increase plasma PCSK9 levels, the effect of niacin on PCSK9 is unknown. We investigated the impact of niacin, atorvastatin, and fenofibrate on PCSK9 levels in 3 distinct studies. A statin-only study randomized 74 hypercholesterolemic patients to placebo, atorvastatin 10 mg/day, or atorvastatin 80 mg/day for 16 weeks. A dose-related increase in PCSK9 was noted such that atorvastatin 80 mg increased PCSK9 by a mean +27% (95% confidence interval [CI] +12 to +42), confirming the effect of statin therapy on raising PCSK9. A second study randomized 70 patients with carotid atherosclerosis to simvastatin 20 mg/day, simvastatin 80 mg/day, or simvastatin 20 mg/extended-release (ER) niacin 2 g/day. PCSK9 levels were increased with statin therapy, but decreased with the simvastatin 20 mg/ER niacin combination (mean -13%, CI -3 to -23). A final study involved 19 dyslipidemic participants on atorvastatin 10 mg with serial addition of fenofibric acid 135 mg followed by ER niacin 2 g/day. Fenofibric acid led to a + 23% (CI +10 to +36, p = 0.001) increase in PCSK9; the addition of niacin resulted in a subsequent -17% decrease (CI -19 to -5, p = 0.004). A positive association was noted between change in PCSK9 and low-density lipoprotein cholesterol levels (r = 0.62, p = 0.006) with the addition of niacin. In conclusion, niacin therapy offsets the increase in PCSK9 levels noted with statin and fibrate therapy. A portion of the low-density lipoprotein cholesterol reduction seen with niacin therapy may be due to reduction in PCSK9. (C) 2015 Elsevier Inc. All rights reserved. C1 [Khera, Amit V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Qamar, Arman; Reilly, Muredach P.; Dunbar, Richard L.; Rader, Daniel J.] Smilow Ctr Translat Res, Dept Med, Perelman Sch Med, Philadelphia, PA USA. [Qamar, Arman; Reilly, Muredach P.; Dunbar, Richard L.; Rader, Daniel J.] Smilow Ctr Translat Res, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA USA. RP Khera, AV (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. EM avkhera@mgh.harvard.edu FU Merck Pharmaceuticals (Whitehouse Station, New Jersey); Abbott Pharmaceuticals (Abbott Park, Illinois); National Center for Research Resources [UL1RR024134] FX The study involving treatment with simvastatin versus extended-release niacin (study 2) was supported by investigator-initiated grants from Merck Pharmaceuticals (Whitehouse Station, New Jersey) and KOS Pharmaceuticals, now Abbott Pharmaceuticals (Abbott Park, Illinois). The study involving sequential therapy with fenofibric acid, atorvastatin, and niacin (study 3) was supported by Abbot Pharmaceuticals (Abbott Park, Illinois) and the National Center for Research Resources, grant UL1RR024134. Companies had no influence on study design, analysis, or manuscript preparation. All authors have approved the final manuscript draft submitted for publication. NR 20 TC 15 Z9 15 U1 0 U2 8 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2015 VL 115 IS 2 BP 178 EP 182 DI 10.1016/j.amjcard.2014.10.018 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ7OJ UT WOS:000348407700005 PM 25432415 ER PT J AU Maan, A Heist, EK Passeri, J Inglessis, I Baker, J Ptaszek, L Vlahakes, G Ruskin, JN Palacios, I Sundt, T Mansour, M AF Maan, Abhishek Heist, E. Kevin Passeri, Jonathan Inglessis, Ignacio Baker, Joshua Ptaszek, Leon Vlahakes, Gus Ruskin, Jeremy N. Palacios, Igor Sundt, Thoralf Mansour, Moussa TI Impact of Atrial Fibrillation on Outcomes in Patients Who Underwent Transcatheter Aortic Valve Replacement SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SURGERY; RISK; ASSOCIATION; PREDICTION; MANAGEMENT; STENOSIS AB Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for surgical high-risk patients with severe aortic stenosis. The aim of this study was to determine the impact of atrial fibrillation (AF) on procedural outcomes. Data from 137 patients who underwent TAVR using Edwards SAPIEN valve were reviewed. The predictors of new-onset atrial fibrillation (NOAF) after the procedure were analyzed. In addition, the post-TAVR clinical outcomes and adverse events were compared according to the presence and absence of preprocedural and postprocedural AF. Previous AF was present in 49% of the patients who underwent TAVR. After the procedure, NOAF was detected in 21% of patients, and the cumulative incidence of post-TAVR AF was 60%. After TAVR, 50% of all the episodes of NOAF occurred in the initial 24 hours after the procedure. Transapical approach was observed to an important predictor of NOAF (adjusted odds ratio [OR] 5.05, 95% confidence interval [CI] 1.40 to 18.20, p = 0.013). The composite outcome of all-cause mortality, stroke, vascular complications, and repeat hospitalization in 1 month after TAVR was significantly higher in patients with previous AF (33 of 67 vs 19 of 70, adjusted OR 2.60, 95% CI 1.22 to 5.54, p = 0.013) compared with patients who did not have previous AF. The presence of post-TAVR AF led to a prolongation in the duration of intensive care unit stay by an average of 70 hours (95% CI 25 to 114.7 hours, p = 0.002). Similarly, post-TAVR AF also led to the prolongation in the hospital stay by an average of 6.7 days (95% CI 4.69 to 8.73 days, p <0.0005). In conclusion, our study demonstrates that the presence of AF before TAVR is an important predictor of the composite end point of all-cause mortality, stroke, vascular complications, and repeat hospitalization in 1 month after the procedure. AF after TAVR is more likely to be encountered with the transapical approach and is associated with a prolongation of intensive care unit and hospital stay. (C) 2015 Elsevier Inc. All rights reserved. C1 [Maan, Abhishek; Heist, E. Kevin; Passeri, Jonathan; Inglessis, Ignacio; Baker, Joshua; Ptaszek, Leon; Vlahakes, Gus; Ruskin, Jeremy N.; Palacios, Igor; Sundt, Thoralf; Mansour, Moussa] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. EM mmansour@mgh.harvard.edu FU Deane Institute for Integrative Research in Atrial Fibrillation and Stroke at Massachusetts General Hospital FX The work was supported in part by the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke at Massachusetts General Hospital. NR 25 TC 12 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2015 VL 115 IS 2 BP 220 EP 226 DI 10.1016/j.amjcard.2014.10.027 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ7OJ UT WOS:000348407700013 PM 25465936 ER PT J AU Kim, JH Sher, S Wang, F Berkstresser, B Shoop, JL Galante, A Al Mheid, I Ghasemzadeh, N Hutter, AM Williams, BR Sperling, LS Weiner, RB Quyyumi, AA Baggish, AL AF Kim, Jonathan H. Sher, Salman Wang, Francis Berkstresser, Brant Shoop, James L. Galante, Angelo Al Mheid, Ibhar Ghasemzadeh, Nima Hutter, Adolph M. Williams, B. Robinson, III Sperling, Laurence S. Weiner, Rory B. Quyyumi, Arshed A. Baggish, Aaron L. TI Impact of American-Style Football Participation on Vascular Function SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CENTRAL ARTERIAL COMPLIANCE; PULSE-WAVE VELOCITY; BLOOD-PRESSURE; CARDIOVASCULAR EVENTS; CONSENSUS DOCUMENT; LEAGUE PLAYERS; RISK-FACTORS; STIFFNESS; HYPERTENSION; MORTALITY AB Although hypertension is common in American-style football (ASF) players, the presence of concomitant vascular dysfunction has not been previously characterized. We sought to examine the impact of ASF participation on arterial stiffness and to compare metrics of arterial function between collegiate ASF participants and nonathletic collegiate controls. Newly matriculated collegiate athletes were studied longitudinally during a single season of ASF participation and were then compared with healthy undergraduate controls. Arterial stiffness was characterized using applanation tonometry (SphygmoCor). ASF participants (n = 32, 18.4 +/- 0.5 years) were evenly comprised of Caucasians (n = 14, 44%) and African-Americans (n = 18, 56%). A single season of ASF participation led to an increase in central aortic pulse pressure (27 +/- 4 vs 34 +/- 8 mm Hg, p <0.001). Relative to controls (n = 47), pulse wave velocity was increased in ASF participants (5.6 +/- 0.7 vs 6.2 +/- 0.9 m/s, p = 0.002). After adjusting for height, weight, body mass index, systolic blood pressure, and diastolic blood pressure, ASF participation was independently predictive of increased pulse wave velocity (0 = 0.33, p = 0.04). In conclusion, ASF participation leads to changes in central hemodynamics and increased arterial stiffness. (C) 2015 Elsevier Inc. All rights reserved. C1 [Kim, Jonathan H.; Sher, Salman; Al Mheid, Ibhar; Ghasemzadeh, Nima; Williams, B. Robinson, III; Sperling, Laurence S.; Quyyumi, Arshed A.] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Wang, Francis; Berkstresser, Brant; Baggish, Aaron L.] Harvard Univ, Univ Hlth Serv, Cambridge, MA 02138 USA. [Shoop, James L.; Galante, Angelo] Georgia Inst Technol, Dept Sports Med, Atlanta, GA 30332 USA. [Hutter, Adolph M.; Weiner, Rory B.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, Boston, MA 02114 USA. RP Kim, JH (reprint author), Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. EM jonathan.kim@emory.edu FU T32 National Institutes of Health Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant, Bethesda, Maryland [HL00745]; American Heart Association, Dallas, Texas [FTF2220328] FX This study was funded, in part, by the T32 National Institutes of Health Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant (HL00745), Bethesda, Maryland (Dr. Kim) and the American Heart Association FTF2220328, Dallas, Texas (Dr. Baggish). The authors have no conflicts of interest to disclose. NR 29 TC 5 Z9 5 U1 0 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2015 VL 115 IS 2 BP 262 EP 267 DI 10.1016/j.amjcard.2014.10.033 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ7OJ UT WOS:000348407700020 PM 25465938 ER PT J AU Hicks, JW Sadovski, O Parkes, J Houle, S Hay, BA Carter, RL Wilson, AA Vasdev, N AF Hicks, Justin W. Sadovski, Oleg Parkes, Jun Houle, Sylvain Hay, Bruce A. Carter, Randall L. Wilson, Alan A. Vasdev, Neil TI Radiosynthesis and ex vivo evaluation of [F-18]-(S)-3-(6-(3-fluoropropoxy)benzo[d]isoxazol-3-yl)-5-(methoxymethyl )oxazolidin-2-one for imaging MAO-B with PET SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Positron emission tomography; Fluorine-18; SL25.1188; MAO-B ID MONOAMINE-OXIDASE-B; POSITRON-EMISSION-TOMOGRAPHY; QUANTITATIVE ENZYME AUTORADIOGRAPHY; HUMAN-BRAIN; RADIOTRACER DEVELOPMENT; ALZHEIMERS-DISEASE; IN-VITRO; INHIBITOR; RADIOLIGAND; ASTROCYTES AB Carbon-11 labeled SL25.1188 ((S)-5-(methoxymethyl)-3-(6-(4,4,4-trifluorobutoxy) benzo[d] isoxazol-3yl) oxazolidin-2-one) is a reversible radiotracer for monoamine oxidase B that was recently evaluated in healthy volunteers by positron emission tomography (PET). Herein we report the preparation and ex vivo evaluation of a fluorinated SL25.1188 derivative as a candidate 18F-labeled PET radiotracer. (S)-3-(6-(3-fluoropropoxy) benzo[d] isoxazol-3-yl)-5-(methoxy methyl) oxazolidin-2-one (1) was labeled with fluorine-18 in 51% uncorrected radiochemical yield having high radiochemical purity (> 98%) and specific activity (109 26 GBq/lmol). Ex vivo biodistribution studies demonstrated low radioactivity retention, specific binding and metabolic stability within rat brains. High uptake of radioactivity in bone is consistent with metabolic defluorination. In vitro binding assays of longer chain fluoroalkoxy derivatives revealed that the length of the carbon chain is an integral feature in MAO-B inhibitor potency and selectivity within this scaffold. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Hicks, Justin W.; Sadovski, Oleg; Parkes, Jun; Houle, Sylvain; Wilson, Alan A.] Ctr Addict & Mental Hlth, Res Imaging Ctr, Toronto, ON M5T 1R8, Canada. [Hicks, Justin W.; Houle, Sylvain; Wilson, Alan A.] Univ Toronto, Inst Med Sci, Toronto, ON M5T 1R8, Canada. [Hay, Bruce A.; Carter, Randall L.] Gen Elect Global Res, Niskayuna, NY 12309 USA. [Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. RP Vasdev, N (reprint author), Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. EM Vasdev.Neil@mgh.harvard.edu FU Ontario Ministry of Research and Innovation FX We would like to thank Dr. Ben Rotstein for helpful discussion. Funding for this work was provided in part by the Ontario Ministry of Research and Innovation (Early Researcher Award to NV). NR 59 TC 2 Z9 3 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 15 PY 2015 VL 25 IS 2 BP 288 EP 291 DI 10.1016/j.bmcl.2014.11.048 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA AY9XQ UT WOS:000347901400028 PM 25488845 ER PT J AU Guo, GW Chmielecki, J Goparaju, C Heguy, A Dolgalev, I Carbone, M Seepo, S Meyerson, M Pass, HI AF Guo, Guangwu Chmielecki, Juliann Goparaju, Chandra Heguy, Adriana Dolgalev, Igor Carbone, Michele Seepo, Sara Meyerson, Matthew Pass, Harvey I. TI Whole-Exome Sequencing Reveals Frequent Genetic Alterations in BAP1, NF2, CDKN2A, and CUL1 in Malignant Pleural Mesothelioma SO CANCER RESEARCH LA English DT Review ID SOMATIC MUTATIONS; CANCER GENOME; ADENOCARCINOMA AB Malignant pleural mesothelioma (MPM) is an aggressive neoplasm associated with asbestos exposure. Although previous studies based on candidate gene approaches have identified important common somatic mutations in MPM, these studies have focused on small sets of genes and have provided a limited view of the genetic alterations underlying this disease. Here, we performed whole-exome sequencing on DNA from 22 MPMs and matched blood samples, and identified 517 somatic mutations across 490 mutated genes. Integrative analysis of mutations and somatic copy-number alterations revealed frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1. Our study presents the first unbiased view of the genomic basis of MPM. (C) 2014 AACR. C1 [Guo, Guangwu; Chmielecki, Juliann; Seepo, Sara; Meyerson, Matthew] Broad Inst Harvard & MIT, Cambridge, MD USA. [Guo, Guangwu; Chmielecki, Juliann; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Guo, Guangwu; Chmielecki, Juliann; Meyerson, Matthew] Ctr Canc Genome Discovery, Dept Med Oncol, Boston, MA USA. [Goparaju, Chandra; Pass, Harvey I.] NYU, Langone Med Ctr, Dept Cardiothorac Surg, New York, NY 10016 USA. [Heguy, Adriana; Dolgalev, Igor] NYU, Langone Med Ctr, Genome Technol Ctr, New York, NY USA. [Carbone, Michele] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Pass, HI (reprint author), NYU, Langone Med Ctr, Dept Cardiothorac Surg, 530 1St Ave,9v, New York, NY 10016 USA. EM Harvey.Pass@nyumc.org OI Dolgalev, Igor/0000-0003-4451-126X FU Broad Institute through a grant from the National Human Genome Research Institute at the NIH [U54HG003067]; NCI EDRN [5U01CA111295-07]; Stephen E. Banner Lung Cancer Foundation; American Cancer Society AstraZeneca Postdoctoral Fellowship FX This work was supported by the Broad Institute through a grant from the National Human Genome Research Institute at the NIH (U54HG003067: Eric S. Lander, principal investigator), and by NCI EDRN 5U01CA111295-07 (H.I. Pass as principal investigator), the Stephen E. Banner Lung Cancer Foundation, and Belluck and Fox. J. Chmielecki was supported by an American Cancer Society AstraZeneca Postdoctoral Fellowship. NR 21 TC 46 Z9 46 U1 5 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2015 VL 75 IS 2 BP 264 EP 269 DI 10.1158/0008-5472.CAN-14-1008 PG 6 WC Oncology SC Oncology GA AZ0LT UT WOS:000347937600004 PM 25488749 ER PT J AU Bailey, ST Westerling, T Brown, M AF Bailey, Shannon T. Westerling, Thomas Brown, Myles TI Loss of Estrogen-Regulated microRNA Expression Increases HER2 Signaling and Is Prognostic of Poor Outcome in Luminal Breast Cancer SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; MOLECULAR PORTRAITS; DOWN-REGULATION; RECEPTOR-ALPHA; LET-7 MICRORNA; TUMOR SUBTYPES; CELLS; PROLIFERATION; TARGET; LIN28 AB Among the genes regulated by estrogen receptor (ER) are miRNAs that play a role in breast cancer signaling pathways. To determine whether miRNAs are involved in ER-positive breast cancer progression to hormone independence, we profiled the expression of 800 miRNAs in the estrogen-dependent human breast cancer cell line MCF7 and its estrogen-independent derivative MCF7:2A (MCF7:2A) using NanoString. We found 78 miRNAs differentially expressed between the two cell lines, including a cluster comprising let-7c, miR99a, and miR125b, which is encoded in an intron of the long noncoding RNA LINC00478. These miRNAs are ER targets in MCF7 cells, and nearby ER binding and their expression are significantly decreased in MCF7:2A cells. The expression of these miRNAs was interrogated in patient samples profiled in The Cancer Genome Atlas (TCGA). Among luminal tumors, these miRNAs are expressed at higher levels in luminal A versus B tumors. Although their expression is uniformly low in luminal B tumors, they are lost only in a subset of luminal A patients. Interestingly, this subset with low expression of these miRNAs had worse overall survival compared with luminal A patients with high expression. We confirmed that miR125b directly targets HER2 and that let-7c also regulates HER2 protein expression. In addition, HER2 protein expression and activity are negatively correlated with let-7c expression in TCGA. In summary, we identified an ER-regulated miRNA cluster that regulates HER2, is lost with progression to estrogen independence, and may serve as a biomarker of poor outcome in ER+ luminal A breast cancer patients. (C) 2014 AACR. C1 [Bailey, Shannon T.; Westerling, Thomas; Brown, Myles] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Bailey, Shannon T.; Westerling, Thomas; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bailey, Shannon T.; Westerling, Thomas; Brown, Myles] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bailey, Shannon T.; Westerling, Thomas; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Brown, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Funct Canc Epigenet, 450 Brookline Ave,D730, Boston, MA 02215 USA. EM myles_brown@dfci.harvard.edu OI Brown, Myles/0000-0002-8213-1658 FU Susan G. Komen for the Cure; NCI [CA080111]; NIDDK [R01 DK074967] FX This work was supported by grants from Susan G. Komen for the Cure (M. Brown), the NCI (P01 CA080111 to M. Brown), and NIDDK (R01 DK074967 to M. Brown). NR 52 TC 17 Z9 17 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2015 VL 75 IS 2 BP 436 EP 445 DI 10.1158/0008-5472.CAN-14-1041 PG 10 WC Oncology SC Oncology GA AZ0LT UT WOS:000347937600021 PM 25388283 ER PT J AU Ben Tanfous, M Sharif-Askari, B Ceppi, F Laaribi, H Gagne, V Rousseau, J Labuda, M Silverman, LB Sallan, SE Neuberg, D Kutok, JL Sinnett, D Laverdiere, C Krajinovic, M AF Ben Tanfous, Mohsen Sharif-Askari, Bahram Ceppi, Francesco Laaribi, Haithem Gagne, Vincent Rousseau, Julie Labuda, Malgorzata Silverman, Lewis B. Sallan, Stephen E. Neuberg, Donna Kutok, Jeffery L. Sinnett, Daniel Laverdiere, Caroline Krajinovic, Maja TI Polymorphisms of Asparaginase Pathway and Asparaginase-Related Complications in Children with Acute Lymphoblastic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID FARBER-CANCER-INSTITUTE; SYNTHETASE EXPRESSION; CELLS; CONSORTIUM; RESISTANCE; TRIAL C1 [Ben Tanfous, Mohsen; Sharif-Askari, Bahram; Ceppi, Francesco; Laaribi, Haithem; Gagne, Vincent; Rousseau, Julie; Labuda, Malgorzata; Sinnett, Daniel; Laverdiere, Caroline; Krajinovic, Maja] CHU St Justine, Ctr Rech, Montreal, PQ H3T 1C5, Canada. [Sinnett, Daniel; Laverdiere, Caroline; Krajinovic, Maja] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. [Krajinovic, Maja] Univ Montreal, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada. [Silverman, Lewis B.; Sallan, Stephen E.] Univ Montreal, Dept Pediat Oncol, Montreal, PQ H3C 3J7, Canada. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Silverman, Lewis B.; Sallan, Stephen E.] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. [Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Krajinovic, M (reprint author), CHU St Justine, Ctr Rech, 3175 Chemin Cote Ste Catherine, Montreal, PQ H3T 1C5, Canada. EM maja.krajinovic@umontreal.ca FU NCI NIH HHS [5 P01CA06848, P01 CA068484] NR 27 TC 7 Z9 7 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2015 VL 21 IS 2 BP 329 EP 334 DI 10.1158/1078-0432.CCR-14-0508 PG 6 WC Oncology SC Oncology GA AZ0MA UT WOS:000347938200014 PM 24907114 ER PT J AU Alagesan, B Contino, G Guimaraes, AR Corcoran, RB Deshpande, V Wojtkiewicz, GR Hezel, AF Wong, KK Loda, M Weissleder, R Benes, C Engelman, JA Bardeesy, N AF Alagesan, Brinda Contino, Gianmarco Guimaraes, Alexander R. Corcoran, Ryan B. Deshpande, Vikram Wojtkiewicz, Gregory R. Hezel, Aram F. Wong, Kwok-Kin Loda, Massimo Weissleder, Ralph Benes, Cyril Engelman, Jeffrey A. Bardeesy, Nabeel TI Combined MEK and PI3K Inhibition in a Mouse Model of Pancreatic Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID KINASE KINASE-1/2 INHIBITOR; DUCTAL ADENOCARCINOMA; EXPRESSION; ONCOGENE; GEMCITABINE; ARRY-142886; AZD6244; TUMORS AB Purpose: Improved therapeutic approaches are needed for the treatment of pancreatic ductal adenocarcinoma (PDAC). As dual MEK and PI3K inhibition is presently being used in clinical trials for patients with PDAC, we sought to test the efficacy of combined targeting of these pathways in PDAC using both in vitro drug screens and genetically engineered mouse models (GEMM). Experimental Design: We performed high-throughput screening of > 500 human cancer cell lines (including 46 PDAC lines), for sensitivity to 50 clinically relevant compounds, including MEK and PI3K inhibitors. We tested the top hit in the screen, the MEK1/2 inhibitor, AZD6244, for efficacy alone or in combination with the PI3K inhibitors, BKM120 or GDC-0941, in a Kras(G12D)-driven GEMM that recapitulates the histopathogenesis of human PDAC. Results: In vitro screens revealed that PDAC cell lines are relatively resistant to single-agent therapies. The response profile to the MEK1/2 inhibitor, AZD6244, was an outlier, showing the highest selective efficacy in PDAC. Although MEK inhibition alone was mainly cytostatic, apoptosis was induced when combined with PI3K inhibitors (BKM120 or GDC-0941). When tested in a PDAC GEMM and compared with the single agents or vehicle controls, the combination delayed tumor formation in the setting of prevention and extended survival when used to treat advanced tumors, although no durable responses were observed. Conclusions: Our studies point to important contributions of MEK and PI3K signaling to PDAC pathogenesis and suggest that dual targeting of these pathways may provide benefit in some patients with PDAC. (C) 2014 AACR. C1 [Alagesan, Brinda; Contino, Gianmarco; Corcoran, Ryan B.; Hezel, Aram F.; Benes, Cyril; Engelman, Jeffrey A.; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Guimaraes, Alexander R.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Guimaraes, Alexander R.; Loda, Massimo; Weissleder, Ralph] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Corcoran, Ryan B.; Hezel, Aram F.; Wong, Kwok-Kin; Benes, Cyril; Engelman, Jeffrey A.; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Deshpande, Vikram] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Bardeesy, N (reprint author), Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM nelbardeesy@partners.org FU AACR/Pancreatic Cancer Action Network; NIH [NCI 2P01CA117969-06]; Dana-Farber/Harvard Cancer Center Gastrointestinal Cancer SPORE grant [P50 CA127003]; NIH training grant [T32 CA071345]; Fondazione Umberto Veronesi, Associazione Italiana per la ricerca sul Cancro; American Italian Cancer Foundation FX This work was supported by grants (to N. Bardeesy) from the AACR/Pancreatic Cancer Action Network, the NIH (NCI 2P01CA117969-06), and Dana-Farber/Harvard Cancer Center Gastrointestinal Cancer SPORE grant P50 CA127003 (to N. Bardeesy and J.A. Engelman). R. B. Corcoran was supported by NIH training grant T32 CA071345. G. Contino was supported by Fondazione Umberto Veronesi, Associazione Italiana per la ricerca sul Cancro and American Italian Cancer Foundation. NR 24 TC 26 Z9 27 U1 3 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2015 VL 21 IS 2 BP 396 EP 404 DI 10.1158/1078-0432.CCR-14-1591 PG 9 WC Oncology SC Oncology GA AZ0MA UT WOS:000347938200021 PM 25348516 ER PT J AU Creech, AL Taylor, JE Maier, VK Wu, X Feeney, CM Udeshi, ND Peach, SE Boehm, JS Lee, JT Carr, SA Jaffe, JD AF Creech, Amanda L. Taylor, Jordan E. Maier, Verena K. Wu, Xiaoyun Feeney, Caitlin M. Udeshi, Namrata D. Peach, Sally E. Boehm, Jesse S. Lee, Jeannie T. Carr, Steven A. Jaffe, Jacob D. TI Building the Connectivity Map of epigenetics: Chromatin profiling by quantitative targeted mass spectrometry SO METHODS LA English DT Article DE Histones; Chromatin; Epigenetics; Proteomics; Mass spectrometry; SILAC ID H3 LYSINE 27; HISTONE H3; METHYLATION; EZH2; MUTATIONS; MOLECULES AB Epigenetic control of genome function is an important regulatory mechanism in diverse processes such as lineage commitment and environmental sensing, and in disease etiologies ranging from neuropsychiatric disorders to cancer. Here we report a robust, high-throughput targeted, quantitative mass spectrometry (MS) method to rapidly profile modifications of the core histones of chromatin that compose the epigenetic landscape, enabling comparisons among cells with differing genetic backgrounds, genomic perturbations, and drug treatments. (C) 2014 ElsevierInc. All rights reserved. C1 [Creech, Amanda L.; Taylor, Jordan E.; Wu, Xiaoyun; Feeney, Caitlin M.; Udeshi, Namrata D.; Peach, Sally E.; Boehm, Jesse S.; Carr, Steven A.; Jaffe, Jacob D.] Broad Inst MIT & Harvard Univ, Cambridge, MA 02142 USA. [Maier, Verena K.; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Lee, Jeannie T.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Jaffe, JD (reprint author), Broad Inst, 415 Main St, Cambridge, MA 02142 USA. EM jjaffe@broadinstitute.org OI Boehm, Jesse/0000-0002-6795-6336 FU Thought Leader Award; Agilent Technologies Foundation; Agilent Technologies, Inc.; [R21 DA025720-02]; [U01 CA164186-02] FX This work was funded in part by R21 DA025720-02 and U01 CA164186-02 to J.D.J. and by a Thought Leader Award and gift to S.A.C. from the Agilent Technologies Foundation and Agilent Technologies, Inc., respectively. NR 13 TC 7 Z9 7 U1 1 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD JAN 15 PY 2015 VL 72 BP 57 EP 64 DI 10.1016/j.ymeth.2014.10.033 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ7PP UT WOS:000348410800009 PM 25448295 ER PT J AU Chandra, A Khullar, D Lee, TH AF Chandra, Amitabh Khullar, Dhruv Lee, Thomas H. TI Addressing the Challenge of Gray-Zone Medicine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DISEASE; PCI C1 [Chandra, Amitabh] Harvard Univ, Kennedy Sch, Cambridge, MA 02138 USA. [Khullar, Dhruv] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Thomas H.] Press Ganey Associates, Boston, MA USA. RP Chandra, A (reprint author), Harvard Univ, Kennedy Sch, Cambridge, MA 02138 USA. NR 5 TC 4 Z9 4 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 15 PY 2015 VL 372 IS 3 BP 203 EP 205 DI 10.1056/NEJMp1409696 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AZ3HX UT WOS:000348119200002 PM 25587945 ER PT J AU Labidi-Galy, SI Clauss, A Ng, V Duraisamy, S Elias, KM Piao, HY Bilal, E Davidowitz, RA Lu, Y Badalian-Very, G Gyorffy, B Kang, UB Ficarro, S Ganesan, S Mills, GB Marto, JA Drapkin, R AF Labidi-Galy, S. I. Clauss, A. Ng, V. Duraisamy, S. Elias, K. M. Piao, H-Y Bilal, E. Davidowitz, R. A. Lu, Y. Badalian-Very, G. Gyoerffy, B. Kang, U-B Ficarro, S. Ganesan, S. Mills, G. B. Marto, J. A. Drapkin, R. TI Elafin drives poor outcome in high-grade serous ovarian cancers and basal-like breast tumors SO ONCOGENE LA English DT Article DE elafin; ovarian cancer; basal-like breast cancer; mitogen; MAP kinase ID MAMMARY EPITHELIAL-CELLS; MICROARRAY DATA; GENOMIC INSTABILITY; FALLOPIAN-TUBE; EXPRESSION; PROTEIN; CARCINOMAS; SURVIVAL; GENES; VALIDATION AB High-grade serous ovarian carcinoma (HGSOC) and basal-like breast cancer (BLBC) share many features including TP53 mutations, genomic instability and poor prognosis. We recently reported that Elafin is overexpressed by HGSOC and is associated with poor overall survival. Here, we confirm that Elafin overexpression is associated with shorter survival in 1000 HGSOC patients. Elafin confers a proliferative advantage to tumor cells through the activation of the MAP kinase pathway. This mitogenic effect can be neutralized by RNA interference, specific antibodies and a MEK inhibitor. Elafin expression in patient-derived samples was also associated with chemoresistance and strongly correlates with bcl-xL expression. We extended these findings into the examination of 1100 primary breast tumors and six breast cancer cell lines. We observed that Elafin is overexpressed and secreted specifically by BLBC tumors and cell lines, leading to a similar mitogenic effect through activation of the MAP kinase pathway. Here too, Elafin overexpression is associated with poor overall survival, suggesting that it may serve as a biomarker and therapeutic target in this setting. C1 [Labidi-Galy, S. I.; Clauss, A.; Ng, V.; Duraisamy, S.; Elias, K. M.; Piao, H-Y; Badalian-Very, G.; Drapkin, R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Labidi-Galy, S. I.; Clauss, A.; Duraisamy, S.; Elias, K. M.; Badalian-Very, G.; Kang, U-B; Ficarro, S.; Marto, J. A.; Drapkin, R.] Harvard Univ, Sch Med, Boston, MA USA. [Elias, K. M.] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. [Bilal, E.; Ganesan, S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. [Davidowitz, R. A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Lu, Y.; Mills, G. B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Gyoerffy, B.] Hungarian Acad Sci, Res Lab Pediat & Nephrol, Budapest, Hungary. [Kang, U-B; Ficarro, S.; Marto, J. A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA. [Drapkin, R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Drapkin, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, JF215D,450 Brookline Ave, Boston, MA 02215 USA. EM ronny_drapkin@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016; OI Drapkin, Ronny/0000-0002-6912-6977; Elias, Kevin/0000-0003-1502-5553; labidi-galy, sana intidhar/0000-0002-0824-3475; Gyorffy, Balazs/0000-0002-5772-3766 FU NIH/NCI SPORE in OC [OC P50-CA105009, U01 CA-152990, R21 CA-156021]; NIH/NINDS [P01 NS047572]; Honorable Tina Brozman 'Tina's Wish' Foundation; Dr Miriam and Sheldon G. Adelson Medical Research Foundation; Robert and Debra First Fund; Gamel Family Fund; Ovarian Cancer Research Fund; Madeline Franchi Ovations for the Cure Fund; Mary Kay Foundation; Sandy Rollman Ovarian Cancer Foundation; Dana-Farber Cancer Institute (DFCI) Strategic Initiative; Executive Council of the Cancer Foundation; New Jersey Commission on Cancer Research; Arthur Sachs/Fulbright/Harvard; La Fondation Philippe; La Fondation de France-Recherche clinique en cancerologie-Aide a la mobilite des chercheurs FX The authors thank Dr Michelle Hirsch for critical review of the manuscript, Laura Selfors of biocomputing analyzes of the RPPA data, and members of the Drapkin laboratory for fruitful discussions. This work was supported by the NIH/NCI SPORE in OC P50-CA105009 (RD), U01 CA-152990 (RD), R21 CA-156021 (RD); NIH/NINDS P01 NS047572 (JM), the Honorable Tina Brozman 'Tina's Wish' Foundation (JM, RD), the Dr Miriam and Sheldon G. Adelson Medical Research Foundation (GBM and RD), The Robert and Debra First Fund (RD), The Gamel Family Fund (RD), the Ovarian Cancer Research Fund (RD), The Madeline Franchi Ovations for the Cure Fund (AC), the Mary Kay Foundation (RD), the Sandy Rollman Ovarian Cancer Foundation (RD), the Dana-Farber Cancer Institute (DFCI) Strategic Initiative (JM), the Executive Council of the Cancer Foundation (SG), and the New Jersey Commission on Cancer Research (SG). SILG is a recipient of grants from Arthur Sachs/Fulbright/Harvard, La Fondation Philippe and La Fondation de France-'Recherche clinique en cancerologie-Aide a la mobilite des chercheurs'. NR 63 TC 8 Z9 8 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JAN 15 PY 2015 VL 34 IS 3 BP 299 EP 309 DI 10.1038/onc.2013.562 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AZ3RY UT WOS:000348145500004 PM 24469047 ER PT J AU Asmal, M Luedemann, C Lavine, CL Mach, LV Balachandran, H Brinkley, C Denny, TN Lewis, MG Anderson, H Pal, R Sok, D Le, K Pauthner, M Hahn, BH Shaw, GM Seaman, MS Letvin, NL Burton, DR Sodroski, JG Haynes, BF Santra, S AF Asmal, Mohammed Luedemann, Corinne Lavine, Christy L. Mach, Linh V. Balachandran, Harikrishnan Brinkley, Christie Denny, Thomas N. Lewis, Mark G. Anderson, Hanne Pal, Ranajit Sok, Devin Le, Khoa Pauthner, Matthias Hahn, Beatrice H. Shaw, George M. Seaman, Michael S. Letvin, Norman L. Burton, Dennis R. Sodroski, Joseph G. Haynes, Barton F. Santra, Sampa TI Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes SO VIROLOGY LA English DT Article DE SHIV; HIV-1 Clade C; Transmitted/founder Env; Mucosal transmission ID RHESUS-MONKEYS; TYPE-1 ISOLATE; NEUTRALIZING ANTIBODIES; LYMPHOCYTE DEPLETION; PATHOGENIC SHIVS; MACAQUES; ENV; AIDS; VACCINATION; CHALLENGE AB Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder (T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman primates. Currently available SHIVs contain HIV-1 any genes from chronically-infected individuals and do not reflect the characteristics of biologically relevant HIV-1 strains that mediate human transmission. We chose to develop clade C SHIVs, as clade C is the major infecting subtype of HIV-1 in the world. We constructed 10 clade C SHIVs expressing Env proteins from T/F viruses. Three of these ten clade C SHIVs (SHIV KB9 C3, SHIV KB9 C4 and SHIV KB9 C5) replicated in naive rhesus monkeys. These three SHIVs are mucosally transmissible and are neutralized by sCD4 and several HIV-1 broadly neutralizing antibodies. However, like natural T/F viruses, they exhibit low Env reactivity and a Tier 2 neutralization sensitivity. Of note, none of the clade C T/F SHIVs elicited detectable autologous neutralizing antibodies in the infected monkeys, even though antibodies that neutralized a heterologous Tier 1 HIV-1 were generated. Challenge with these three new clade C SHIVs will provide biologically relevant tests for vaccine protection in rhesus macaques. (C) 2014 Elsevier Inc. All rights reserved. C1 [Asmal, Mohammed; Luedemann, Corinne; Lavine, Christy L.; Mach, Linh V.; Balachandran, Harikrishnan; Seaman, Michael S.; Santra, Sampa] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Hahn, Beatrice H.; Shaw, George M.; Letvin, Norman L.] Univ Penn, Dept Med & Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02215 USA. [Brinkley, Christie; Denny, Thomas N.; Haynes, Barton F.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Lewis, Mark G.; Anderson, Hanne] BIOQUAL Inc, Rockville, MD 20852 USA. [Pal, Ranajit] Adv BioSci Labs Inc, Rockville, MD 20850 USA. [Sok, Devin; Le, Khoa; Pauthner, Matthias; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA. RP Santra, S (reprint author), Beth Israel Deaconess Med Ctr, E CLS-1038, Boston, MA 02215 USA. EM ssantra@bidmc.harvard.edu FU Center for HIV/AIDS Vaccine Immunology-Immunogen Design (CHAVI-ID) [UM1-AI00645]; Bill and Melinda Gates Foundation [OPP1033104]; NIH [HHSN272201100022C, HHSN2722013000013]; Harvard University Center for AIDS Research grant NIH [P30-AI060354]; New England Primate Research Center base grant NIH [OD011103] FX We acknowledge Dr. Amber Hoggatt, Mathew Beck, Gerald Learn, Charlene Shaver, and Jake Yalley-Ogunro for their assistance. This work was funded by the Center for HIV/AIDS Vaccine Immunology-Immunogen Design (CHAVI-ID) UM1-AI00645, Bill and Melinda Gates Foundation OPP1033104, NIH contracts HHSN272201100022C and HHSN2722013000013, Harvard University Center for AIDS Research grant NIH P30-AI060354, New England Primate Research Center base grant NIH OD011103. NR 37 TC 8 Z9 9 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 0042-6822 J9 VIROLOGY JI Virology PD JAN 15 PY 2015 VL 475 BP 37 EP 45 DI 10.1016/j.virol.2014.10.032 PG 9 WC Virology SC Virology GA AZ4FE UT WOS:000348176500004 PM 25462344 ER PT J AU Chen, YB Batchelor, T Li, SL Hochberg, E Brezina, M Jones, S Del Rio, C Curtis, M Ballen, KK Barnes, J Chi, AS Dietrich, J Driscoll, J Gertsner, ER Hochberg, F LaCasce, AS McAfee, SL Spitzer, TR Nayak, L Armand, P AF Chen, Yi-Bin Batchelor, Tracy Li, Shuli Hochberg, Ephraim Brezina, Mark Jones, Sooae Del Rio, Candice Curtis, Morgan Ballen, Karen K. Barnes, Jeffrey Chi, Andrew S. Dietrich, Jorg Driscoll, Jessica Gertsner, Elizabeth R. Hochberg, Fred LaCasce, Ann S. McAfee, Steven L. Spitzer, Thomas R. Nayak, Lakshmi Armand, Philippe TI Phase 2 Trial of High-Dose Rituximab With High-Dose Cytarabine Mobilization Therapy and High-Dose Thiotepa, Busulfan, and Cyclophosphamide Autologous Stem Cell Transplantation in Patients With Central Nervous System Involvement by Non-Hodgkin Lymphoma SO CANCER LA English DT Article DE autologous transplant; central nervous system (CNS) lymphoma; rituximab; thiotepa; busulfan; cyclophosphamide (TBC); thiotepa ID PRIMARY CNS LYMPHOMA; WHOLE-BRAIN RADIOTHERAPY; RECURRENT PRIMARY CNS; STUDY-GROUP DSHNHL; INTENSIVE CHEMOTHERAPY; INTRAOCULAR LYMPHOMA; CEREBROSPINAL-FLUID; 1ST-LINE TREATMENT; CONSOLIDATING RADIOTHERAPY; MARROW-TRANSPLANTATION AB BACKGROUNDHigh-dose thiotepa, busulfan, and cyclophosphamide (TBC) with autologous stem cell transplantation (ASCT) has been used in patients with central nervous system (CNS) involvement by non-Hodgkin lymphoma (NHL). Despite limited penetration into the CNS, rituximab is active in primary CNS NHL. Therefore, high-dose rituximab was combined with TBC for ASCT in patients with CNS NHL. METHODSA single-arm phase 2 trial using high-dose rituximab with cytarabine for stem cell mobilization followed by high-dose rituximab combined with thiotepa, busulfan, and cyclophosphamide (R-TBC) for ASCT was conducted. Doses of rituximab at 1000 mg/m(2) were given on days 1 and 8 of mobilization and on days -9 and -2 of TBC. The primary endpoint was efficacy. RESULTSThirty patients were enrolled. Eighteen patients had primary CNS NHL (12 with complete remission (CR)/first partial remission (PR1) and 6 with CR/PR2), and 12 patients had secondary CNS lymphoma (5 with CR/PR1 and 7 with CR/PR2 or beyond). All patients were in partial or complete remission. Twenty-nine patients proceeded to R-TBC ASCT. Two patients developed significant neurotoxicity. The 100-day nonrelapse mortality rate was 0%, and 1 patient died because of nonrelapse causes 5 months after ASCT. For all patients, at a median follow-up of 24 months (range, 12-40 months), the estimated 2-year progression-free survival rate was 81% (95% confidence interval, 59%-92%), and the 2-year overall survival rate was 93% (95% confidence interval, 76%-98%). There were no relapses or deaths among the 18 patients with primary CNS lymphoma. CONCLUSIONSFor patients with CNS involvement by B-cell NHL and especially for patients with primary CNS NHL, R-TBC ASCT shows encouraging activity and merits further study. Cancer 2015;121:226-33. (c) 2014 American Cancer Society. Using high-dose systemic rituximab may allow higher concentrations to penetrate the central nervous system. This article presents a phase 2 trial combining high-dose rituximab with standard autologous stem cell transplantation and shows compelling results in patients with central nervous system involvement by non-Hodgkin lymphoma. C1 [Chen, Yi-Bin; Del Rio, Candice; Curtis, Morgan; Ballen, Karen K.; Driscoll, Jessica] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Batchelor, Tracy; Jones, Sooae; Chi, Andrew S.; Dietrich, Jorg; Gertsner, Elizabeth R.; Hochberg, Fred] Massachusetts Gen Hosp, Div Neurooncol, Boston, MA 02114 USA. [Li, Shuli] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hochberg, Ephraim; Brezina, Mark; Barnes, Jeffrey; McAfee, Steven L.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [LaCasce, Ann S.; Armand, Philippe] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Nayak, Lakshmi] Dana Farber Canc Inst, Div Neurooncol, Boston, MA 02115 USA. RP Chen, YB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Bone Marrow Transplant Unit,Med Sch, Cox 108,55 Fruit St, Boston, MA 02114 USA. EM ychen6@partners.org FU Otsuka Pharmaceuticals; National Institutes of Health [CA 006516] FX Yi-Bin Chen and Philippe Armand received funding from Otsuka Pharmaceuticals to conduct this and other clinical trials. Shuli Li's work is partially supported by National Institutes of Health grant CA 006516. NR 45 TC 13 Z9 13 U1 0 U2 2 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 JAN 15 PY 2015 VL 121 IS 2 BP 226 EP 233 DI 10.1002/cncr.29023 PG 8 WC Oncology SC Oncology GA AY4IH UT WOS:000347540900009 PM 25204639 ER PT J AU Alderfer, MA Zelley, K Lindell, RB Novokmet, A Mai, PL Garber, JE Nathan, D Scollon, S Chun, NM Patenaude, AF Ford, JM Plon, SE Schiffman, JD Diller, LR Savage, SA Malkin, D Ford, CA Nichols, KE AF Alderfer, Melissa A. Zelley, Kristin Lindell, Robert B. Novokmet, Ana Mai, Phuong L. Garber, Judy E. Nathan, Deepika Scollon, Sarah Chun, Nicolette M. Patenaude, Andrea F. Ford, James M. Plon, Sharon E. Schiffman, Joshua D. Diller, Lisa R. Savage, Sharon A. Malkin, David Ford, Carol A. Nichols, Kim E. TI Parent Decision-Making Around the Genetic Testing of Children for Germline TP53 Mutations SO CANCER LA English DT Article DE genetic testing; Li-Fraumeni syndrome; decision-making; pediatrics; cancer ID LI-FRAUMENI-SYNDROME; CANCER PREDISPOSITION; ISSUES; UPDATE; RISK AB BACKGROUNDLi-Fraumeni syndrome is a rare genetic cancer predisposition syndrome caused by germline TP53 mutations. Up to 20% of mutation carriers develop cancer during childhood. The benefits of TP53 mutation testing of children are a matter of debate and knowledge of parent decision-making around such testing is limited. The current study examined how parents make decisions regarding TP53 testing for their children. METHODSFamilies offered and those pursuing TP53 testing for their children were identified across the study sites. Qualitative interviews with 46 parents (39 families) were analyzed to describe decision-making styles and perceived advantages and disadvantages of testing. RESULTSTP53 mutation testing uptake was high (92%). Three decision-making styles emerged. Automatic decisions (44% of decisions) involved little thought and identified immediate benefit(s) in testing (100% pursued testing). Considered decisions (49%) weighed the risks and benefits but were made easily (77% pursued testing). Deliberated decisions (6%) were difficult and focused on psychosocial concerns (25% pursued testing). Perceived advantages of testing included promoting child health, satisfying a need to know, understanding why cancer(s) occurred, suggesting family member risk, and benefiting research. Disadvantages included psychosocial risks and privacy/discrimination/insurance issues. CONCLUSIONSAlthough empirical evidence regarding the benefits and risks of TP53 testing during childhood are lacking, the majority of parents in the current study decided easily in favor of testing and perceived a range of advantages. The authors conclude that in the context of a clinical diagnosis of Li-Fraumeni syndrome, parents should continue to be offered TP53 testing for their children, counseled regarding potential risks and benefits, and supported in their decision-making process. Cancer 2015;121:286-93. (c) 2014 American Cancer Society. Li-Fraumeni Syndrome (LFS) is a rare genetic cancer predisposition syndrome caused by germline TP53 mutations in which up to 20% of mutation carriers develop cancer during childhood. Although empirical evidence regarding benefits and risks of TP53 testing during childhood are lacking, most parents in our study decided easily in favor of testing and perceived a range of advantages that outweighed risks. C1 [Alderfer, Melissa A.; Zelley, Kristin; Lindell, Robert B.; Nichols, Kim E.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Alderfer, Melissa A.; Ford, Carol A.; Nichols, Kim E.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Novokmet, Ana; Malkin, David] Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Mai, Phuong L.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Garber, Judy E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA. [Garber, Judy E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Nathan, Deepika; Schiffman, Joshua D.] Univ Utah, Huntsman Canc Inst, High Risk Canc Clin, Salt Lake City, UT USA. [Nathan, Deepika; Schiffman, Joshua D.] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Scollon, Sarah; Plon, Sharon E.] Texas Childrens Canc Ctr, Canc Genet & Genom Program, Houston, TX USA. [Scollon, Sarah; Plon, Sharon E.] Texas Childrens Hematol Ctr, Canc Genet & Genom Program, Houston, TX USA. [Chun, Nicolette M.; Ford, James M.] Stanford Univ, Med Ctr, Canc Genet Program, Stanford, CA 94305 USA. [Patenaude, Andrea F.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Patenaude, Andrea F.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Ford, James M.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Ford, James M.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. [Plon, Sharon E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Plon, Sharon E.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Schiffman, Joshua D.] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Diller, Lisa R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childhood Canc Survivor Program, Boston, MA 02115 USA. [Diller, Lisa R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Malkin, David] Univ Toronto, Dept Pediat, Toronto, ON, Canada. [Ford, Carol A.] Childrens Hosp Philadelphia, Div Adolescent Med, Philadelphia, PA 19104 USA. RP Alderfer, MA (reprint author), Nemours Alfred I duPont Hosp Children, Ctr Healthcare Delivery Sci, 1600 Rockland Rd, Wilmington, DE 19803 USA. EM melissa.alderfer@nemours.org RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU University of Pennsylvania Center for the Integration of Genetic Healthcare Technologies (Penn-CIGHT); Center for Childhood Cancer Research at The Children's Hospital of Philadelphia; Alex's Lemonade Stand Foundation FX Supported by grants from The University of Pennsylvania Center for the Integration of Genetic Healthcare Technologies (Penn-CIGHT), the Center for Childhood Cancer Research at The Children's Hospital of Philadelphia, and Alex's Lemonade Stand Foundation. NR 14 TC 5 Z9 5 U1 1 U2 7 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 JAN 15 PY 2015 VL 121 IS 2 BP 286 EP 293 DI 10.1002/cncr.29027 PG 8 WC Oncology SC Oncology GA AY4IH UT WOS:000347540900016 PM 25223899 ER PT J AU Hamnvik, OPR Choueiri, TK Turchin, A McKay, RR Goyal, L Davis, M Kaymakcalan, MD Williams, JS AF Hamnvik, Ole-Petter R. Choueiri, Toni K. Turchin, Alexander McKay, Rana R. Goyal, Lipika Davis, Michael Kaymakcalan, Marina D. Williams, Jonathan S. TI Clinical Risk Factors for the Development of Hypertension in Patients Treated With Inhibitors of the VEGF Signaling Pathway SO CANCER LA English DT Article DE hypertension; antihypertensive agents; angiogenesis inhibitors; risk factors; survival; sunitinib; sorafenib; pazopanib ID RENAL-CELL CARCINOMA; CANCER-PATIENTS; BLOOD-PRESSURE; METAANALYSIS; SUNITINIB; SORAFENIB; BIOMARKER; SURVIVAL; EFFICACY; AXITINIB AB BACKGROUNDVEGF signaling pathway inhibitor (anti-VEGF) therapy is associated with hypertension, but little is known about predisposing clinical characteristics. This study describes the real-world association between baseline clinical characteristics, blood pressure (BP) response, and survival in patients prescribed anti-VEGF therapies. METHODSClinical data from Partners HealthCare in Massachusetts was obtained from adults treated with anti-VEGF therapies (2002-2013). Treatment-induced hypertensive response was defined as worsening of preexisting hypertension or new diagnosis of hypertension (if no prior hypertension history). RESULTSData from 1120 patients with renal cell carcinoma (32.2%), hepatocellular carcinoma (11.6%), gastrointestinal stromal tumors (12.5%), and other sarcomas (15.3%) were analyzed. Most patients received sunitinib (52%), sorafenib (25.9%), or pazopanib (18%). A treatment-induced hypertensive response was identified in 49.7% of treated patients. Preexisting hypertension, present in 65.4%, was an independent risk factor for BP elevation (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.27-1.92); other risk factors included age 60 years (OR, 1.26; 95% CI, 1.06-1.52), and body mass index (BMI) 25 kg/m(2) (OR, 1.26; 95% CI, 1.04-1.53). Race, sex, anti-VEGF therapy prescribed, and baseline antihypertensive class were not significant risk factors. The absolute observed mean increase in BP was 21 mm Hg (systolic)/15 mm Hg (diastolic), both in patients with and without preexisting hypertension. The development of hypertension predicted improved survival (hazard ratio, 0.76; 95% CI, 0.65-0.89). CONCLUSIONSPreexisting hypertension, age, and BMI identify patients at risk for significant anti-VEGF therapy-induced BP elevation. Hypertension appears to be a clinical biomarker of efficacy of anti-VEGF therapies in a broad range of malignancies. Cancer 2015;121:311-9. (c) 2014 American Cancer Society. Older age, higher body mass index, and preexisting hypertension are risk factors for the development of a treatment-induced hypertensive response to VEGF signaling pathway inhibitors. The development of hypertension was associated with improved survival. C1 [Hamnvik, Ole-Petter R.; Turchin, Alexander; Davis, Michael; Williams, Jonathan S.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Choueiri, Toni K.; McKay, Rana R.; Kaymakcalan, Marina D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goyal, Lipika] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Williams, JS (reprint author), 221 Longwood Ave,RFB 2, Boston, MA 02115 USA. EM jwilliams5@partners.org OI Williams, Jonathan/0000-0001-7152-765X FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [1UL1 TR001102-01]; Michael Brigham funds for Kidney Cancer Research FX This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 1UL1 TR001102-01) and financial contributions from Harvard University and its affiliated academic health care centers, as well as the Trust Family and Michael Brigham funds for Kidney Cancer Research (to T.K.C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic health care centers, or the National Institutes of Health. NR 31 TC 21 Z9 21 U1 0 U2 7 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 JAN 15 PY 2015 VL 121 IS 2 BP 311 EP 319 DI 10.1002/cncr.28972 PG 9 WC Oncology SC Oncology GA AY4IH UT WOS:000347540900019 PM 25236375 ER PT J AU Rooney, MS Shukla, SA Wu, CJ Getz, G Hacohen, N AF Rooney, Michael S. Shukla, Sachet A. Wu, Catherine J. Getz, Gad Hacohen, Nir TI Molecular and Genetic Properties of Tumors Associated with Local Immune Cytolytic Activity SO CELL LA English DT Article ID CASEIN KINASE-II; T-CELLS; INDUCED APOPTOSIS; CANCER-CELLS; DOWN-REGULATION; EXPRESSION; SURVIVAL; RESISTANCE; LANDSCAPE; MELANOMA AB How the genomic landscape of a tumor shapes and is shaped by anti-tumor immunity has not been systematically explored. Using large-scale genomic data sets of solid tissue tumor biopsies, we quantified the cytolytic activity of the local immune infiltrate and identified associated properties across 18 tumor types. The number of predicted MHC Class I-associated neoantigens was correlated with cytolytic activity and was lower than expected in colorectal and other tumors, suggesting immune-mediated elimination. We identified recurrently mutated genes that showed positive association with cytolytic activity, including beta-2-microglobulin (B2M), HLA-A, -B and -C and Caspase 8 (CASP8), highlighting loss of antigen presentation and blockade of extrinsic apoptosis as key strategies of resistance to cytolytic activity. Genetic amplifications were also associated with high cytolytic activity, including immunosuppressive factors such as PDL1/2 and ALOX12B/15B. Our genetic findings thus provide evidence for immunoediting in tumors and uncover mechanisms of tumor-intrinsic resistance to cytolytic activity. C1 [Rooney, Michael S.; Shukla, Sachet A.; Wu, Catherine J.; Getz, Gad; Hacohen, Nir] Broad Inst, Cambridge, MA 02142 USA. [Rooney, Michael S.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02141 USA. [Shukla, Sachet A.; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Catherine J.; Hacohen, Nir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. RP Hacohen, N (reprint author), Broad Inst, Cambridge, MA 02142 USA. EM nhacohen@mgh.harvard.edu FU Blavatinik Family Foundation; MGH Research Scholars Program; NIH Training Programin Bioinformatics and Integrative Genomics training FX We are grateful to the TCGA Research Network (http://cancergenome.nih.gov/), the Genotype-Tissue Expression (GTEx) Project (dbGaP phs000424.v3.p1), the FANTOM research consortium (http://fantom.gsc.riken.jp/), and the Broad-Novartis Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home) for providing the data analyzed in this manuscript. We thank Mara Rosenberg, Amaro Taylor-Weiner, Chloe Villani, Arnon Arazi, Pavan Bachireddy, and Dan-Avi Landau for their feedback and help accessing data and analysis tools and Leslie Gaffney for assistance with artwork. Funding was provided by the Blavatinik Family Foundation (N.H.), the MGH Research Scholars Program (N.H.), and the NIH Training Programin Bioinformatics and Integrative Genomics training grant (M.S.R.). G.G. is a consultant to the KEW Group. NR 62 TC 187 Z9 189 U1 18 U2 68 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 15 PY 2015 VL 160 IS 1-2 BP 48 EP 61 DI 10.1016/j.cell.2014.12.033 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ0GD UT WOS:000347923200008 PM 25594174 ER PT J AU Tamplin, OJ Durand, EM Carr, LA Childs, SJ Hagedorn, EJ Li, PL Yzaguirre, AD Speck, NA Zon, LI AF Tamplin, Owen J. Durand, Ellen M. Carr, Logan A. Childs, Sarah J. Hagedorn, Elliott J. Li, Pulin Yzaguirre, Amanda D. Speck, Nancy A. Zon, Leonard I. TI Hematopoietic Stem Cell Arrival Triggers Dynamic Remodeling of the Perivascular Niche SO CELL LA English DT Article ID GROWTH-FACTOR-BETA; BONE-MARROW NICHE; AORTIC ENDOTHELIUM; PROGENITOR CELLS; SELF-RENEWAL; MOUSE EMBRYO; ZEBRAFISH; MAINTENANCE; TRANSPLANTATION; ENGRAFTMENT AB Hematopoietic stem and progenitor cells (HSPCs) can reconstitute and sustain the entire blood system. We generated a highly specific transgenic reporter of HSPCs in zebrafish. This allowed us to perform high-resolution live imaging on endogenous HSPCs not currently possible in mammalian bone marrow. Using this system, we have uncovered distinct interactions between single HSPCs and their niche. When an HSPC arrives in the perivascular niche, a group of endothelial cells remodel to form a surrounding pocket. This structure appears conserved in mouse fetal liver. Correlative light and electron microscopy revealed that endothelial cells surround a single HSPC attached to a single mesenchymal stromal cell. Live imaging showed that mesenchymal stromal cells anchor HSPCs and orient their divisions. A chemical genetic screen found that the compound lycorine promotes HSPC-niche interactions during development and ultimately expands the stem cell pool into adulthood. Our studies provide evidence for dynamic niche interactions upon stem cell colonization. C1 [Tamplin, Owen J.; Durand, Ellen M.; Carr, Logan A.; Hagedorn, Elliott J.; Li, Pulin; Zon, Leonard I.] Harvard Univ, Sch Med, Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Tamplin, Owen J.; Durand, Ellen M.; Carr, Logan A.; Hagedorn, Elliott J.; Li, Pulin; Zon, Leonard I.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Tamplin, Owen J.; Durand, Ellen M.; Carr, Logan A.; Hagedorn, Elliott J.; Li, Pulin; Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Durand, Ellen M.; Zon, Leonard I.] Harvard Univ, Cambridge, MA 02138 USA. [Childs, Sarah J.] Univ Calgary, Alberta Childrens Hosp Res Inst, Calgary, AB T2N 4N1, Canada. [Li, Pulin; Zon, Leonard I.] Harvard Univ, Chem Biol Program, Cambridge, MA 02138 USA. [Yzaguirre, Amanda D.; Speck, Nancy A.] Univ Penn, Abramson Family Canc Res Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Yzaguirre, Amanda D.; Speck, Nancy A.] Univ Penn, Dept Cell & Dev Biol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU HHMI; NIH [R01 HL04880, 5P30 DK49216, 5R01 DK53298, 5U01 HL10001-05, R24 DK092760, R01 HL091724, U01HL100405, 1F31HL120615]; American Society of Hematology; Heart and Stroke Foundation of Canada; Canadian Institutes of Health Research (CIHR) [MOP-97787]; Alberta Innovates Health Solutions; Helen Hay Whitney Foundation FX We thank the following for their support and contributions: L. Cameron for confocal imaging (Dana Farber Cancer Institute); T. Schlaeger, S. Datta, and P.D. Manos for chemical screening (Boston Children's Hospital [BCH]); R. Mathieu for flow cytometry (BCH); L. Bu and A. Hill for confocal imaging (BCH); H.A. Feldman and W. London for statistical analysis (BCH); T.P. Ward and Y. Zhou for computer support (BCH); J. Hutchinson, O.M. Hofmann, and W.A. Hide for microarray analysis (Harvard School of Public Health); M. Ericsson and E.J. Benecchi for conventional electron microscopy (Harvard Medical School); A. Roholt for serial block face scanning EM (Renovo Neural, Cleveland, USA); T. Fuerstenhaupt for guidance in EM tomographic reconstructions (University of Calgary); and T. Bowman for immunohistochemistry (Brigham and Women's Hospital). We thank T.V. Bowman, J.R. Perlin, and C.K. Kaufman for critical reading of this manuscript. This work was supported by HHMI and NIH grants R01 HL04880, 5P30 DK49216, 5R01 DK53298, 5U01 HL10001-05, and R24 DK092760 (to L.I.Z.); R01 HL091724 and U01HL100405 (to N.A.S.); and 1F31HL120615 (to A.D.Y.). O.J.T. was supported by the American Society of Hematology, Canadian Institutes of Health Research (CIHR), and Heart and Stroke Foundation of Canada. S.J.C. was supported by CIHR (MOP-97787) and Alberta Innovates Health Solutions. E.J.H. was supported by a Helen Hay Whitney Foundation Fellowship. L.I.Z. is a founder and stockholder of Fate Therapeutics, Inc. and Scholar Rock and is a scientific advisor for Stemgent. NR 38 TC 60 Z9 61 U1 4 U2 35 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 15 PY 2015 VL 160 IS 1-2 BP 241 EP 252 DI 10.1016/j.cell.2014.12.032 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ0GD UT WOS:000347923200022 PM 25594182 ER PT J AU Nerya, FC da Hora, CC Yaqub, U Zhang, X McCarthy, DM Bhide, PG Irimia, D Breakefield, XO AF Nerya, Flavia C. da Hora, Cintia C. Yaqub, Uzma Zhang, Xuan McCarthy, Deirdre M. Bhide, Pradeep G. Irimia, Daniel Breakefield, Xandra O. TI New methods for investigation of neuronal migration in embryonic brain explants SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Neuron migration; MGE explant; Microfluidic device; Transduction ID FOREBRAIN AB Background: Proper migration of neurons is essential for the formation and normal functioning of the nervous system. Defects in neuronal migration underlie a number of neurologic diseases in humans. Although cell migration is crucial for neural development, molecular mechanisms guiding neuronal migration remain to be elucidated fully. Newborn neurons from the embryonic medial ganglionic eminence (MGE) migrate a long distance dorsally in the developing brain, giving rise to several types of interneurons in the neocortex. New method: In this study, we developed an immunocytochemistry (ICC) protocol to stain neurons migrating out of the MGE explant embedded in Matrigel. We also established a protocol to efficiently transfect cells in MGE explants, achieving a transduction efficiency of more than 30%. Comparison with existing method: In addition, we developed microfluidic chambers for explants that allow visualization of the vectorial migration of individual neurons from mouse embryonic MGE explants. Our microfluidic system allows monitoring of the distribution of cellular organelles (e.g. Golgi) within migrating neurons which have been stained with commercial molecular dyes or transfected with adeno-associated virus (AAV) expressing reporter proteins. Conclusion: These methods provide new paradigms to study neuronal migration in real-time. (C) 2014 Elsevier B.V. All rights reserved. C1 [Nerya, Flavia C.; da Hora, Cintia C.; Yaqub, Uzma; Zhang, Xuan; McCarthy, Deirdre M.; Bhide, Pradeep G.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Boston, MA 02114 USA. [Nerya, Flavia C.; da Hora, Cintia C.; Yaqub, Uzma; Zhang, Xuan; McCarthy, Deirdre M.; Bhide, Pradeep G.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [McCarthy, Deirdre M.; Bhide, Pradeep G.] Florida State Univ, Coll Med, Dept Biomed Sci, Ctr Brain Repair, Tallahassee, FL 32306 USA. [Irimia, Daniel] Massachusetts Gen Hosp, Dept Surg, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. RP Nerya, FC (reprint author), Massachusetts Gen Hosp East, Mol Neurogenet Unit, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM neryfc@yahoo.com OI Irimia, Daniel/0000-0001-7347-2082; Bhide, Pradeep/0000-0003-4236-9415 FU NIH/NINDS [P50 NS037409, GM092804]; Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine; NIH/NIBIB BioMEMS Resource Center [EB002503] FX The authors thank Ms. Suzanne McDavitt for skilled editorial assistance. We also thank Igor Bagayev and Dr. Cristopher Bragg at MGH Neuroscience Center Confocal Microscope Facility. This work was supported by NIH/NINDS Grant P50 NS037409 (XOB and PB) and GM092804 (DI), and The Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine (FCN). Lentivirus and AAV vectors were kindly provided by Dr. Miguel Sena-Esteves (UMass Medical School, Worcester, MA). Microfabrication procedures were performed at the NIH/NIBIB BioMEMS Resource Center (EB002503). NR 17 TC 3 Z9 3 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 15 PY 2015 VL 239 BP 80 EP 84 DI 10.1016/j.jneumeth.2014.09.028 PG 5 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AY6GE UT WOS:000347664400009 PM 25291524 ER PT J AU Banks, AS McAllister, FE Camporez, JPG Zushin, PJH Jurczak, MJ Laznik-Bogoslavski, D Shulman, GI Gygi, SP Spiegelman, BM AF Banks, Alexander S. McAllister, Fiona E. Camporez, Joao Paulo G. Zushin, Peter-James H. Jurczak, Michael J. Laznik-Bogoslavski, Dina Shulman, Gerald I. Gygi, Steven P. Spiegelman, Bruce M. TI An ERK/Cdk5 axis controls the diabetogenic actions of PPAR gamma SO NATURE LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; ACTIVATED PROTEIN-KINASE; INSULIN SENSITIVITY; MASS-SPECTROMETRY; MEK INHIBITION; PHOSPHORYLATION; MODULATION; GLUCOSE; OBESE; CDK5 AB Obesity-linked insulin resistance is a major precursor to the development of type 2 diabetes. Previous work has shown that phosphorylation of PPAR gamma (peroxisome proliferator-activated receptor gamma) at serine 273 by cydin-dependent kinase 5 (Cdk5) stimulates diabetogenic gene expression in adipose tissues(1). Inhibition of this modification is a key therapeutic mechanism for anti-diabetic drugs that bind PPAR gamma, such as the thiazolidinediones and PPAR gamma partial agonists or non-agonists(2). For a better understanding of the importance of this obesity-linked PPAR gamma phosphorylation, we created mice that ablated Cdk5 specifically in adipose tissues. These mice have both a paradoxical increase in PPAR gamma phosphorylation at serine 273 and worsened insulin resistance. Unbiased proteomic studies show that extracellular signal-regulated kinase (ERK) kinases are activated in these knockout animals. Here we show that ERK directly phosphorylates serine 273 of PPAR gamma in a robust manner and that Cdk5 suppresses ERKs through direct action on a novel site in MAP kinase/ ERK kinase (MEK). Importantly, pharmacological inhibition of MEK and ERK markedly improves insulin resistance in both obese wildtype and ob/ob mice, and also completely reverses the deleterious effects of the Cdk5 ablation. These data show that an ERK/Cdk5 axis controls PPAR gamma function and suggest that MEK/ERK inhibitors may hold promise for the treatment of type 2 diabetes. C1 [Banks, Alexander S.; Zushin, Peter-James H.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Banks, Alexander S.; Zushin, Peter-James H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [McAllister, Fiona E.; Gygi, Steven P.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Camporez, Joao Paulo G.; Jurczak, Michael J.; Shulman, Gerald I.] Yale Univ, Sch Med, Yale Mouse Metab Phenotyping Ctr, New Haven, CT 06510 USA. [Camporez, Joao Paulo G.; Jurczak, Michael J.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Camporez, Joao Paulo G.; Jurczak, Michael J.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Laznik-Bogoslavski, Dina; Spiegelman, Bruce M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Banks, AS (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 75 Francis St, Boston, MA 02115 USA. EM abanks@research.bwh.harvard.edu; bruce_spiegelman@dfci.harvard.edu RI Camporez, Joao Paulo/B-9122-2015; Banks, Alexander/B-4832-2012 OI Banks, Alexander/0000-0003-1787-6925 FU National Institutes of Health (NIH) [DK31405, DK93638]; Harvard University Milton Fund FX We thank E. Rosen for providing us with the adiponectin Cre mice before their initial publication; members of the Spiegelman laboratory (Dana-Farber Cancer Institute) and D. Cohen (Brigham and Women's Hospital) for discussions; and C. Palmer and K. LeClair for reading the manuscript. B.M.S. acknowledges National Institutes of Health (NIH) grant DK31405. A.B. acknowledges NIH grant DK93638, the Harvard University Milton Fund, and the Harvard Digestive Disease Center, Core D. NR 44 TC 55 Z9 55 U1 6 U2 45 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 15 PY 2015 VL 517 IS 7534 BP 391 EP U581 DI 10.1038/nature13887 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY8NK UT WOS:000347810300051 PM 25409143 ER PT J AU Konhilas, JP Chen, H Luczak, E Mckee, LA Regan, J Watson, PA Stauffer, BL Khalpey, ZI Mckinsey, TA Horn, T LaFleur, B Leinwand, LA AF Konhilas, John P. Chen, Hao Luczak, Elizabeth Mckee, Laurel A. Regan, Jessica Watson, Peter A. Stauffer, Brian L. Khalpey, Zain I. Mckinsey, Timothy A. Horn, Todd LaFleur, Bonnie Leinwand, Leslie A. TI Diet and sex modify exercise and cardiac adaptation in the mouse SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiac hypertrophy; sex and exercise; diet; soy ID ACTIVATED PROTEIN-KINASE; ENDURANCE EXERCISE; SKELETAL-MUSCLE; HYPERTROPHIC CARDIOMYOPATHY; GENDER-DIFFERENCES; HEART-FAILURE; MICE; WHEEL; SUBSTRATE; PATHWAY AB The heart adapts to exercise stimuli in a sex-dimorphic manner when mice are fed the traditional soy-based chow. Females undergo more voluntary exercise (4 wk) than males and exhibit more cardiac hypertrophy per kilometer run (18, 32). We have found that diet plays a critical role in cage wheel exercise and cardiac adaptation to the exercise stimulus in this sex dimorphism. Specifically, feeding male mice a casein-based, soy-free diet increases daily running distance over soy-fed counterparts to equal that of females. Moreover, casein-fed males have a greater capacity to increase their cardiac mass in response to exercise compared with soy-fed males. To further explore the biochemical mechanisms for these differences, we performed a candidate-based RT-PCR screen on genes previously implicated in diet-or exercise-based cardiac hypertrophy. Of the genes screened, many exhibit significant exercise, diet, or sex effects but only transforming growth factor-beta 1 shows a significant three-way interaction with no genes showing a two-way interaction. Finally, we show that the expression and activity of adenosine monophosphate-activated kinase-alpha 2 and acetyl-CoA carboxylase is dependent on exercise, diet, and sex. C1 [Konhilas, John P.; Luczak, Elizabeth; Stauffer, Brian L.; Leinwand, Leslie A.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Konhilas, John P.; Chen, Hao; Mckee, Laurel A.; Regan, Jessica] Univ Arizona, Dept Physiol, Sarver Mol Cardiovasc Res Program, Tucson, AZ 85721 USA. [Watson, Peter A.] Univ Colorado, Denver, CO 80202 USA. [Watson, Peter A.; Stauffer, Brian L.; Mckinsey, Timothy A.; Horn, Todd] Denver Vet Affairs Med Ctr, Denver, CO USA. [Watson, Peter A.; Stauffer, Brian L.; Mckinsey, Timothy A.; Horn, Todd] Univ Colorado, Dept Med, Div Cardiol, Denver, CO USA. [Stauffer, Brian L.] Denver Hlth Med Ctr, Dept Med, Div Cardiol, Denver, CO USA. [Khalpey, Zain I.] Univ Arizona, Dept Surg, Tucson, AZ 85721 USA. [LaFleur, Bonnie] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85721 USA. RP Konhilas, JP (reprint author), Univ Arizona, Dept Physiol, Sarver Mol Cardiovasc Res Program, 1656 E Mabel St,Med Res Bldg,Rm 320, Tucson, AZ 85721 USA. EM konhilas@arizona.edu OI Stauffer, Brian/0000-0003-3418-7750 FU National Heart, Lung, and Blood Institute [HL-50560, HL-098256]; National and Mentored Research Science Development Award [K01-AR-052840]; National Heart, Lung, and Blood Institute Independent Scientist Award [K02-HL-105799] FX This work was supported by National Heart, Lung, and Blood Institute Grants HL-50560 (to L. A. Leinwand) and HL-098256, National and Mentored Research Science Development Award K01-AR-052840, and National Heart, Lung, and Blood Institute Independent Scientist Award K02-HL-105799 (to J. P. Konhilas). NR 43 TC 5 Z9 5 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN 15 PY 2015 VL 308 IS 2 BP H135 EP H145 DI 10.1152/ajpheart.00532.2014 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA AY0WW UT WOS:000347315900008 PM 25398983 ER PT J AU Janzon, M James, S Cannon, CP Storey, RF Mellstrom, C Nicolau, JC Wallentin, L Henriksson, M AF Janzon, M. James, S. Cannon, C. P. Storey, R. F. Mellstrom, C. Nicolau, J. C. Wallentin, L. Henriksson, M. TI Health economic analysis of ticagrelor in patients with acute coronary syndromes intended for non-invasive therapy SO HEART LA English DT Article ID MYOCARDIAL-INFARCTION; MEDICAL-MANAGEMENT; PLATO TRIAL; CLOPIDOGREL; OUTCOMES; STRATEGY; REVASCULARIZATION; INTERVENTION; PREDICTORS AB Objective To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management. Methods A previously developed cost effectiveness model was used to estimate long-term costs and outcomes for patients scheduled for non-invasive management. Healthcare costs, event rates and health-related quality of life under treatment with either ticagrelor or clopidogrel over 12 months were estimated from the PLATO study. Long-term costs and health outcomes were estimated based on data from PLATO and published literature sources. To investigate the importance of different healthcare cost structures and life expectancy for the results, the analysis was carried out from the perspectives of the Swedish, UK, German and Brazilian public healthcare systems. Results Ticagrelor was associated with lifetime quality-adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 in the UK, 0.17 in Germany and 0.13 in Brazil compared with generic clopidogrel, with increased healthcare costs of (sic)467, (sic)551, (sic)739 and (sic)574, respectively. The cost per QALY gained with ticagrelor was (sic)2747, (sic)3395, (sic)4419 and (sic)4471 from a Swedish, UK, German and Brazilian public healthcare system perspective, respectively. Probabilistic sensitivity analyses indicated that the cost per QALY gained with ticagrelor was below conventional threshold values of cost effectiveness with a high probability. Conclusions Treatment of patients with ACS scheduled for 12 months' non-invasive management with ticagrelor is associated with a cost per QALY gained below conventional threshold values of cost effectiveness compared with generic clopidogrel. C1 [Janzon, M.] Linkoping Univ, Dept Cardiol, Linkoping, Sweden. [Janzon, M.] Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden. [Janzon, M.; Henriksson, M.] Linkoping Univ, Ctr Med Technol Assessment, Dept Med & Hlth Sci, Div Hlth Care Anal, Linkoping, Sweden. [James, S.; Wallentin, L.] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [James, S.; Wallentin, L.] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Cannon, C. P.] Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. [Cannon, C. P.] Harvard Univ, Sch Med, Boston, MA USA. [Storey, R. F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Mellstrom, C.] AstraZeneca R&D, Molndal, Sweden. [Nicolau, J. C.] Univ Sao Paulo Med Sch, Heart Inst InCor, Sao Paulo, Brazil. [Henriksson, M.] AstraZeneca Nord Balt, Sodertalje, Sweden. RP Janzon, M (reprint author), Linkoping Univ Hosp, Dept Cardiol, SE-58185 Linkoping, Sweden. EM magnus.janzon@liu.se RI Nicolau, Jose/E-1487-2012 FU AstraZeneca FX The PLATO study was funded by AstraZeneca. NR 23 TC 2 Z9 2 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD JAN 15 PY 2015 VL 101 IS 2 BP 119 EP 125 DI 10.1136/heartjnl-2014-305864 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AY3BP UT WOS:000347459800008 PM 25227704 ER PT J AU Murali, MR Uyeda, JW Tingpej, B AF Murali, Mandakolathur R. Uyeda, Jennifer W. Tingpej, Bhatraphol TI Case 2-2015: A 25-Year-Old Man with Abdominal Pain, Syncope, and Hypotension SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CYSTIC ECHINOCOCCOSIS; ANAPHYLAXIS; SHOCK C1 [Murali, Mandakolathur R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Uyeda, Jennifer W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Tingpej, Bhatraphol] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Murali, Mandakolathur R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Uyeda, Jennifer W.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Tingpej, Bhatraphol] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Murali, MR (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 14 TC 3 Z9 3 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 15 PY 2015 VL 372 IS 3 BP 265 EP 273 DI 10.1056/NEJMcpc1410939 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AZ3HX UT WOS:000348119200012 PM 25587951 ER PT J AU McCleery, A Lee, J Joshi, A Wynn, JK Hellemann, GS Green, MF AF McCleery, Amanda Lee, Junghee Joshi, Aditi Wynn, Jonathan K. Hellemann, Gerhard S. Green, Michael F. TI Meta-Analysis of Face Processing Event-Related Potentials in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Emotion identification; ERP; Face processing; N170; N250; Schizophrenia ID FACIAL AFFECT RECOGNITION; SOCIAL COGNITION; EMOTION RECOGNITION; PERCEPTION; N170; DEFICITS; EXPRESSIONS; PSYCHOSIS; REPRESENTATIONS; STANDARDIZATION AB BACKGROUND: Schizophrenia is associated with impaired face processing. N170 and N250 are two event-related potentials that have been studied in relation to face processing in schizophrenia, but the results have been mixed. The aim of this article was to conduct a meta-analysis of N170 and N250 in schizophrenia to evaluate trends and resolve the inconsistencies. METHODS: Twenty-one studies of N170 (n = 438 schizophrenia patients, n = 418 control subjects) and six studies of N250 (n = 149 schizophrenia patients, n = 151 control subjects) were evaluated. Hedges' g was calculated for each study, and the overall weighted mean effect size (ES) was calculated for N170 and N250. Homogeneity of the ES distributions, potential publication bias, and impact of potential moderators were also assessed. RESULTS: The amplitude of both N170 and N250 to face stimuli was smaller in patients than control subjects (N170 ES = .64; N250 ES = .49; ps < .001). The distributions of the ES were homogeneous (ps > .90), and there was no indication of a publication bias. We found no significant effect of task requirements regarding judgments of the face stimuli. Moreover, we found no significant difference between the ES for N170 and N250. CONCLUSIONS: Though findings of individual studies have been mixed, the results of the meta-analysis strongly support disruption of N170 and N250 in schizophrenia. The comparable effect sizes across the two waveforms suggest that the well-established behavioral deficit in face emotion processing is mirrored in an underlying neural impairment for processing faces. C1 [McCleery, Amanda; Lee, Junghee; Wynn, Jonathan K.; Hellemann, Gerhard S.; Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Joshi, Aditi] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Wynn, Jonathan K.; Green, Michael F.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP McCleery, A (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, UCLA Semel Inst Neurosci & Human Behav, 300 Med Plaza,Room 2213, Los Angeles, CA 90095 USA. EM amccleery@mednet.ucla.edu RI Lee, Junghee/C-5226-2014; McCleery, Amanda/D-5471-2016; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; McCleery, Amanda/0000-0003-2714-6897; Wynn, Jonathan/0000-0002-1763-8540 FU Canadian Institutes of Health Research fellowship award; Amgen FX Dr. McCleery is supported by the Canadian Institutes of Health Research fellowship award.; Dr. Green has been a consultant to AbbVie, Biogen, DSP, EnVivo, and Roche, and he is on the scientific advisory board of Mnemosyne. He has received research funds from Amgen. All other authors declare no biomedical financial interests or potential conflicts of interest. NR 63 TC 9 Z9 10 U1 4 U2 21 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 JAN 15 PY 2015 VL 77 IS 2 BP 116 EP 126 DI 10.1016/j.biopsych.2014.04.015 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AW6NQ UT WOS:000346386600007 PM 24923618 ER PT J AU Cannon, TD Chung, Y He, G Sun, DQ Jacobson, A van Erp, TGM McEwen, S Addington, J Bearden, CE Cadenhead, K Cornblatt, B Mathalon, DH McGlashan, T Perkins, D Jeffries, C Seidman, LJ Tsuang, M Walker, E Woods, SW Heinssen, R AF Cannon, Tyrone D. Chung, Yoonho He, George Sun, Daqiang Jacobson, Aron van Erp, Theo G. M. McEwen, Sarah Addington, Jean Bearden, Carrie E. Cadenhead, Kristin Cornblatt, Barbara Mathalon, Daniel H. McGlashan, Thomas Perkins, Diana Jeffries, Clark Seidman, Larry J. Tsuang, Ming Walker, Elaine Woods, Scott W. Heinssen, Robert CA North Amer Prodrome Longitudinal S TI Progressive Reduction in Cortical Thickness as Psychosis Develops: A Multisite Longitudinal Neuroimaging Study of Youth at Elevated Clinical Risk SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Inflammation; MRI; Prefrontal cortex; Prodromal; Psychosis; Schizophrenia ID ULTRA-HIGH-RISK; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE; NEUROANATOMICAL ABNORMALITIES; ANTIPSYCHOTIC TREATMENT; HIPPOCAMPAL VOLUME; INDIVIDUALS; SCHIZOPHRENIA; BRAIN AB BACKGROUND: Individuals at clinical high risk (CHR) who progress to fully psychotic symptoms have been observed to show a steeper rate of cortical gray matter reduction compared with individuals without symptomatic progression and with healthy control subjects. Whether such changes reflect processes associated with the pathophysiology of schizophrenia or exposure to antipsychotic drugs is unknown. METHODS: In this multisite study, 274 CHR cases, including 35 individuals who converted to psychosis, and 135 healthy comparison subjects were scanned with magnetic resonance imaging at baseline, 12-month follow-up, or the point of conversion for the subjects who developed fully psychotic symptoms. RESULTS: In a traveling subjects substudy, excellent reliability was observed for measures of cortical thickness and subcortical volumes. Controlling for multiple comparisons throughout the brain, CHR subjects who converted to psychosis showed a steeper rate of gray matter loss in the right superior frontal, middle frontal, and medial orbitofrontal cortical regions as well as a greater rate of expansion of the third ventricle compared with CHR subjects who did not convert to psychosis and healthy control subjects. Differential tissue loss was present in subjects who had not received antipsychotic medications during the interscan interval and was predicted by baseline levels of an aggregate measure of proinflammatory cytokines in plasma. CONCLUSIONS: These findings demonstrate that the brain changes are not explained by exposure to antipsychotic drugs but likely play a role in psychosis pathophysiology. Given that the cortical changes were more pronounced in subjects with briefer durations of prodromal symptoms, contributing factors may predominantly play a role in acuteonset forms of psychosis. C1 [Cannon, Tyrone D.; Chung, Yoonho; He, George; Jacobson, Aron] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Cannon, Tyrone D.; McGlashan, Thomas; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Sun, Daqiang; McEwen, Sarah; Bearden, Carrie E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Sun, Daqiang; McEwen, Sarah; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [van Erp, Theo G. M.] Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Cadenhead, Kristin; Tsuang, Ming] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Cornblatt, Barbara] Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY USA. [Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Perkins, Diana] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Jeffries, Clark] Univ N Carolina, Renaissance Comp Inst, Chapel Hill, NC USA. [Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Walker, Elaine] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Heinssen, Robert] NIMH, Div Treatment & Prevent Res, Rockville, MD 20857 USA. RP Cannon, TD (reprint author), Yale Univ, Dept Psychol, 2 Hillhouse Ave,POB 208205, New Haven, CT 06520 USA. EM tyrone.cannon@yale.edu FU National Institute of Mental Health (NIMH) at the National Institutes of Health [MH081902, MH081857, MH081988, MH081928, MH082004, MH082022, MH081984, MH066160]; NIMH [P50 MH066286, P50 MH080272]; Commonwealth of Massachusetts [SCDMH82101008006] FX This work was supported by a collaborative U01 award from the National Institute of Mental Health (NIMH) at the National Institutes of Health (Grant Nos. MH081902 [TDC], MH081857 [BC], MH081988 [EW], MH081928 [LJS], MH082004 [DP], MH082022 [KC], MH081984 [JA], and MH066160 [SWW]) and NIMH Grant No. P50 MH066286 (CEB), NIMH Grant No. P50 MH080272, and the Commonwealth of Massachusetts (Grant No. SCDMH82101008006 [LJS]). NR 64 TC 74 Z9 74 U1 15 U2 41 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 JAN 15 PY 2015 VL 77 IS 2 BP 147 EP 157 DI 10.1016/j.biopsych.2014.05.023 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AW6NQ UT WOS:000346386600010 PM 25034946 ER PT J AU Dowling, NM Johnson, SC Gleason, CE Jagust, WJ AF Dowling, N. Maritza Johnson, Sterling C. Gleason, Carey E. Jagust, William J. CA Alzheimers Dis Neuroimaging Initia TI The mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function SO NEUROIMAGE LA English DT Article DE CSF biomarkers; Beta amyloid; FDG-PET; Tau; Alzheimer's disease; Longitudinal mediation; Parallel process latent growth; Structural equation modeling ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; PRECLINICAL ALZHEIMERS-DISEASE; BRAIN GLUCOSE-METABOLISM; MINI-MENTAL-STATE; APOLIPOPROTEIN-E; CSF BIOMARKERS; MEASUREMENT INVARIANCE; AMYLOID BURDEN; GENETIC RISK AB Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imagingmarkers of neural function, and cognition has not been described. Using a statistical mediation model, we examined relationships between cerebrospinal fluid (CSF) analytes (hyperphosphorylated tau (p-Tau(181p)), beta-amyloid peptides 1-42 (A beta(1-42)), total tau (t-Tau), and their ratios); change in cognitive function; and change in [18F] fluorodeoxyglucose (FDG) uptake using positron emission tomography (PET). We hypothesized that a) abnormal CSF protein values at baseline, result in cognitive declines by decreasing neuronal glucose metabolism across time, and b) the role of altered glucose metabolism in the assumed causal chain varies by brain region and the nature of CSF protein alteration. Data from 412 individuals participating in Alzheimer's Disease Neuroimaging (ADNI) cohort studies were included in analyses. At baseline, individuals were cognitively normal (N = 82), or impaired: 241 with mild cognitive impairment, and 89 with Alzheimer's disease. A parallel-process latent growth curve model was used to test mediational effects of changes in regional FDG-PET uptake over time in relation to baseline CSF biomarkers and changes in cognition, measured with the 13-item Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-Cog). Findings suggested a causal sequence of events; specifically, FDG hypometabolism acted as a mediator between antecedent CSF biomarker alterations and subsequent cognitive impairment. Higher baseline concentrations of t-Tau, and p-Tau181p were more predictive of decline in cerebral glucose metabolism than lower baseline concentrations of A beta(1-42). FDG-PET changes appeared to mediate t-Tau or t-Tau/A beta(1-42)-associated cognitive change across all brain regions examined. Significant direct effects of alterations in A beta(1-42) levels on hypometabolism were observed in a single brain region: middle/inferior temporal gyrus. Results support a temporal framework model in which reduced CSF amyloid-related biomarkers occur earlier in the pathogenic pathway, ultimately leading to detrimental cognitive effects. Also consistent with this temporal framework model, baseline markers of neurofibrillary degeneration predicted changes in brain glucose metabolism in turn causing longitudinal cognitive changes, suggesting that tau-related burden precedes neurometabolic dysfunction. While intriguing, the hypothesized mediational relationships require further validation. Published by Elsevier Inc. C1 [Dowling, N. Maritza] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53792 USA. [Dowling, N. Maritza; Johnson, Sterling C.; Gleason, Carey E.] Univ Wisconsin, Alzheimers Dis Res Ctr, Madison, WI 53792 USA. [Johnson, Sterling C.; Gleason, Carey E.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Jagust, William J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA. RP Dowling, NM (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53792 USA. EM nmdowlin@biostat.wisc.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; Alzheimer's Association [NIRG-12-242799]; National Institutes of Health [NIH-AG021155] FX Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare;; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.; This research also was partially supported by a grant from the Alzheimer's Association (NIRG-12-242799, Dowling) and the National Institutes of Health (NIH-AG021155, Johnson). NR 81 TC 7 Z9 8 U1 4 U2 28 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 JAN 15 PY 2015 VL 105 BP 357 EP 368 DI 10.1016/j.neuroimage.2014.10.050 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AW1LG UT WOS:000346050300034 PM 25450107 ER PT J AU Shafee, R Buckner, RL Fischl, B AF Shafee, Rebecca Buckner, Randy L. Fischl, Bruce TI Gray matter myelination of 1555 human brains using partial volume corrected MRI images SO NEUROIMAGE LA English DT Article DE Myelin; MRI; Cortical development; Partial volume effect ID HUMAN CEREBRAL-CORTEX; INTRINSIC FUNCTIONAL CONNECTIVITY; ANTERIOR CINGULATE CORTEX; MAGNETIC-RESONANCE IMAGES; SURFACE-BASED ANALYSIS; HUMAN VISUAL-CORTEX; HIGH-RESOLUTION MRI; CORTICAL AREAS; WHITE-MATTER; IRON CONCENTRATION AB Themyelin content of the cortex changes over the human lifetime and aberrant cortical myelination is associated with diseases such as schizophrenia and multiple sclerosis. Recently magnetic resonance imaging (MRI) techniques have shown potential in differentiating between myeloarchitectonically distinct cortical regions in vivo. Here we introduce a new algorithm for correcting partial volume effects present in mm-scale MRI images which was used to investigate the myelination pattern of the cerebral cortex in 1555 clinically normal subjects using the ratio of T1-weighted (T1w) and T2-weighted (T2w) MRI images. A significant linear cross-sectional age increase in T1w/T2w estimated myelin was detected across an 18 to 35 year age span (highest value of similar to 1%/year compared to mean T1w/T2w myelin value at 18 years). The cortex was divided at mid-thickness and the value of T1w/T2w myelin calculated for the inner and outer layers separately. The increase in T1w/T2w estimated myelin occurs predominantly in the inner layer for most cortical regions. The ratio of the inner and outer layer T1w/T2w myelin was further validated using high-resolution in vivo MRI scans and also a high-resolution MRI scan of a postmortem brain. Additionally, the relationships between cortical thickness, curvature and T1w/T2w estimated myelin were found to be significant, although the relationships varied across the cortex. We discuss these observations as well as limitations of using the T1w/T2w ratio as an estimate of cortical myelin. (C) 2014 Elsevier Inc. All rights reserved. C1 [Shafee, Rebecca; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buckner, Randy L.; Fischl, Bruce] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Buckner, Randy L.; Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Shafee, Rebecca] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Shafee, Rebecca] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Fischl, B (reprint author), 149 Thirteenth St,Rm 2301, Charlestown, MA 02129 USA. EM shafee@genetics.med.harvard.edu; randy_buckner@harvard.edu; Fischl@nmr.mgh.harvard.edu FU Center for Brain Science Neuroinformatics Research Group; Athinoula A. Martinos Center for Biomedical Imaging; Center for Human Genetic Research; HHMI; National Center for Research Resources [U24 RR021382]; National Institute of Biomedical Imaging and Bioengineering [5P41EB015896-15, R01EB006758]; National Institute on Aging [AG022381, 5R01AG008122-22, R01 AG016495-11]; National Center for Complementary and Alternative Medicine [RC1 AT005728-01]; National Institute of Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963]; Shared Instrumentation Grants [1S10RR023401, 1S10RR019307, 1S10RR023043]; Autism & Dyslexia Project - Ellison Medical Foundation; NIH Blueprint for Neuroscience Research, multi-institutional Human Connectome Project [5U01-MH093765] FX Data were provided [in part] by the Brain Genomics Superstruct Project of Harvard University and the Massachusetts General Hospital, (Principal Investigators: Randy Buckner, Joshua Roffman, and Jordan Smoller), with support from the Center for Brain Science Neuroinformatics Research Group, the Athinoula A. Martinos Center for Biomedical Imaging, and the Center for Human Genetic Research. 20 individual investigators at Harvard and MGH generously contributed data to the overall project. Support for this research was provided by HHMI, the National Center for Research Resources (U24 RR021382), the National Institute of Biomedical Imaging and Bioengineering (5P41EB015896-15, R01EB006758), the National Institute on Aging (AG022381, 5R01AG008122-22, R01 AG016495-11), the National Center for Complementary and Alternative Medicine (RC1 AT005728-01), and the National Institute of Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation, and by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. NR 58 TC 17 Z9 17 U1 1 U2 17 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 JAN 15 PY 2015 VL 105 BP 473 EP 485 DI 10.1016/j.neuroimage.2014.10.054 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AW1LG UT WOS:000346050300043 PM 25449739 ER PT J AU Rigotti, NA Wu, M AF Rigotti, Nancy A. Wu, Mark TI Advising patients about electronic cigarettes SO EUROPEAN HEART JOURNAL LA English DT Editorial Material C1 [Rigotti, Nancy A.; Wu, Mark] Boston Univ, Sch Med, Boston, MA 02118 USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. RP Rigotti, NA (reprint author), Boston Univ, Sch Med, Boston, MA 02118 USA. EM nrigotti@partners.org; Mark_Wu@hms.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JAN 14 PY 2015 VL 36 IS 3 BP 135 EP 136 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE1QT UT WOS:000351587700004 PM 25741552 ER PT J AU Adamala, K Engelhart, AE Szostak, JW AF Adamala, Katarzyna Engelhart, Aaron E. Szostak, Jack W. TI Generation of Functional RNAs from Inactive Oligonucleotide Complexes by Non-enzymatic Primer Extension SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID TEMPLATE-DIRECTED SYNTHESIS; GROUP-I INTRON; HAMMERHEAD RIBOZYME; REPLICATION STEPS; NUCLEIC-ACIDS; CLEAVAGE; ENZYME; MODEL; OLIGOMERIZATION; RECONSTITUTION AB The earliest genomic RNAs had to be short enough for efficient replication, while simultaneously serving as unfolded templates and effective ribozymes. A partial solution to this paradox may lie in the fact that many functional RNAs can self-assemble from multiple fragments. Therefore, in early evolution, genomic RNA fragments could have been significantly shorter than unimolecular functional RNAs. Here, we show that unstable, nonfunctional complexes assembled from even shorter 3'-truncated oligonucleotides can be stabilized and gain function via non-enzymatic primer extension. Such short RNAs could act as good templates due to their minimal length and complex-forming capacity, while their minimal length would facilitate replication by relatively inefficient polymerization reactions. These RNAs could also assemble into nascent functional RNAs and undergo conversion to catalytically active forms, by the same polymerization chemistry used for replication that generated the original short RNAs. Such phenomena could have substantially relaxed requirements for copying efficiency in early nonenzymatic replication systems C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu OI Adamala, Kate/0000-0003-1066-7207 FU Simons Collaboration on the Origin of Life; NASA Postdoctoral Program through NASA Astrobiology; NASA; Massachusetts General Hospital Executive Committee on Research FX The authors thank Dr. Neha Kamat for helpful discussions and supplying activated nucleotides and members of the Szostak lab for helpful comments on the manuscript. This research was supported in part by a grant from the Simons Collaboration on the Origin of Life to J.W.S. A.E.E. was supported by an appointment to the NASA Postdoctoral Program through NASA Astrobiology, administered by Oak Ridge Associated Universities through a contract with NASA, and a Tosteson Fellowship from the Massachusetts General Hospital Executive Committee on Research. J.W.S. is an Investigator of the Howard Hughes Medical Institute. NR 42 TC 5 Z9 5 U1 3 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 14 PY 2015 VL 137 IS 1 BP 483 EP 489 DI 10.1021/ja511564d PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8RY UT WOS:000348483500079 PM 25521912 ER PT J AU Roberts, AM Ware, JS Herman, DS Schafer, S Baksi, J Bick, AG Buchan, RJ Walsh, R John, S Wilkinson, S Mazzarotto, F Felkin, LE Gong, SS MacArthur, JAL Cunningham, F Flannick, J Gabriel, SB Altshuler, DM Macdonald, PS Heinig, M Keogh, AM Hayward, CS Banner, NR Pennell, DJ O'Regan, DP San, TR De Marvao, A Dawes, TJW Gulati, A Birks, EJ Yacoub, MH Radke, M Gotthardt, M Wilson, JG O'Donnell, CJ Prasad, SK Barton, PJR Fatkin, D Hubner, N Seidman, JG Seidman, CE Cook, SA AF Roberts, Angharad M. Ware, James S. Herman, Daniel S. Schafer, Sebastian Baksi, John Bick, Alexander G. Buchan, Rachel J. Walsh, Roddy John, Shibu Wilkinson, Samuel Mazzarotto, Francesco Felkin, Leanne E. Gong, Sungsam MacArthur, Jacqueline A. L. Cunningham, Fiona Flannick, Jason Gabriel, Stacey B. Altshuler, David M. Macdonald, Peter S. Heinig, Matthias Keogh, Anne M. Hayward, Christopher S. Banner, Nicholas R. Pennell, Dudley J. O'Regan, Declan P. San, Tan Ru De Marvao, Antonio Dawes, Timothy J. W. Gulati, Ankur Birks, Emma J. Yacoub, Magdi H. Radke, Michael Gotthardt, Michael Wilson, James G. O'Donnell, Christopher J. Prasad, Sanjay K. Barton, Paul J. R. Fatkin, Diane Hubner, Norbert Seidman, Jonathan G. Seidman, Christine E. Cook, Stuart A. TI Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID CARDIOVASCULAR MAGNETIC-RESONANCE; FAMILIAL DILATED CARDIOMYOPATHY; HEART-FAILURE; PROGNOSTIC VALUE; RISK-FACTORS; POPULATION; VARIANTS; MUTATIONS; SEQUENCE; GENES AB The recent discovery of heterozygous human mutations that truncate full-length titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as a common cause of end-stage dilated cardiomyopathy (DCM) promises new prospects for improving heart failure management. However, realization of this opportunity has been hindered by the burden of TTN-truncating variants (TTNtv) in the general population and uncertainty about their consequences in health or disease. To elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac phenotyping in 5267 individuals across the spectrum of cardiac physiology and integrated these data with RNA and protein analyses of human heart tissues. We report diversity of TTN isoform expression in the heart, define the relative inclusion of TTN exons in different isoforms (using the TTN transcript annotations available at http://cardiodb.org/titin), and demonstrate that these data, coupled with the position of the TTNtv, provide a robust strategy to discriminate pathogenic from benign TTNtv. We show that TTNtv is the most common genetic cause of DCM in ambulant patients in the community, identify clinically important manifestations of TTNtv-positive DCM, and define the penetrance and outcomes of TTNtv in the general population. By integrating genetic, transcriptome, and protein analyses, we provide evidence for a length-dependent mechanism of disease. These data inform diagnostic criteria and management strategies for TTNtv-positive DCM patients and for TTNtv that are identified as incidental findings. C1 [Roberts, Angharad M.; O'Regan, Declan P.; De Marvao, Antonio; Dawes, Timothy J. W.; Cook, Stuart A.] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England. [Roberts, Angharad M.; Ware, James S.; Baksi, John; Buchan, Rachel J.; Walsh, Roddy; John, Shibu; Wilkinson, Samuel; Mazzarotto, Francesco; Felkin, Leanne E.; Gong, Sungsam; Pennell, Dudley J.; Gulati, Ankur; Prasad, Sanjay K.; Barton, Paul J. R.] Royal Brompton & Harefield Natl Hlth Serv NHS Fdn, Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London SW3 6NP, England. [Roberts, Angharad M.; Ware, James S.; Baksi, John; Buchan, Rachel J.; Walsh, Roddy; John, Shibu; Wilkinson, Samuel; Mazzarotto, Francesco; Felkin, Leanne E.; Gong, Sungsam; Pennell, Dudley J.; Gulati, Ankur; Prasad, Sanjay K.; Barton, Paul J. R.] Univ London Imperial Coll Sci Technol & Med, London SW3 6NP, England. [Ware, James S.; Mazzarotto, Francesco; Felkin, Leanne E.; Banner, Nicholas R.; Pennell, Dudley J.; Birks, Emma J.; Yacoub, Magdi H.; Barton, Paul J. R.; Cook, Stuart A.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6NP, England. [Ware, James S.; Herman, Daniel S.; Bick, Alexander G.; Seidman, Jonathan G.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Ware, James S.; Herman, Daniel S.; Bick, Alexander G.; Flannick, Jason; Gabriel, Stacey B.; Altshuler, David M.; Seidman, Christine E.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Ware, James S.; Herman, Daniel S.; Bick, Alexander G.; Flannick, Jason; Gabriel, Stacey B.; Altshuler, David M.; Seidman, Christine E.] MIT, Cambridge, MA 02142 USA. [Herman, Daniel S.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Schafer, Sebastian; Heinig, Matthias] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. [MacArthur, Jacqueline A. L.; Cunningham, Fiona] Wellcome Trust Genome Campus, European Bioinformat Inst, European Mol Biol Lab, Hinxton CB10 1SD, Cambs, England. [Flannick, Jason] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Macdonald, Peter S.; Keogh, Anne M.; Hayward, Christopher S.; Fatkin, Diane] St Vincents Hosp, Dept Cardiol, Darlinghurst, NSW 2010, Australia. [Macdonald, Peter S.; Keogh, Anne M.; Hayward, Christopher S.; Fatkin, Diane] Victor Chang Cardiac Res Inst, Darlinghurst, NSW 2010, Australia. [Macdonald, Peter S.; Keogh, Anne M.; Hayward, Christopher S.; Fatkin, Diane] Univ New S Wales, Fac Med, Kensington, NSW 2052, Australia. [Banner, Nicholas R.] Harefield Hosp, Royal Brompton & Harefield NHS Fdn Trust, Harefield UB9 6JH, Middx, England. [San, Tan Ru; Cook, Stuart A.] Natl Heart Ctr, Singapore 169609, Singapore. [Birks, Emma J.] Univ Louisville, Dept Med, Louisville, KY 40202 USA. [Birks, Emma J.] Jewish Hosp, Louisville, KY 40202 USA. [Radke, Michael; Gotthardt, Michael] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. [Gotthardt, Michael] German Ctr Cardiovasc Res, D-13347 Berlin, Germany. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [O'Donnell, Christopher J.] NHLBI, FraminghamHeart Study, Framingham, MA 01702 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Hubner, Norbert] Charite, D-10117 Berlin, Germany. [Seidman, Christine E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Seidman, Christine E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Cook, Stuart A.] Duke Natl Univ Singapore, Singapore 169857, Singapore. RP Cook, SA (reprint author), Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England. EM cseidman@genetics.med.harvard.edu; stuart.cook@nhcs.com.sg RI Mazzarotto, Francesco/E-1843-2017; OI Mazzarotto, Francesco/0000-0002-6159-9980; Felkin, Leanne/0000-0003-1402-8314; Barton, Paul/0000-0002-1165-7767; Schafer, Sebastian/0000-0002-6909-8275; Gotthardt, Michael/0000-0003-1788-3172; Gong, Sungsam/0000-0001-5796-4423; Walsh, Roddy/0000-0001-5092-8825; de Marvao, Antonio/0000-0001-9095-5887; Ware, James/0000-0002-6110-5880 FU NIHR Biomedical Research Unit in Cardiovascular Disease at Royal Brompton & Harefield NHS Foundation Trust; Imperial College London; NIHR Imperial Biomedical Research Centre; British Heart Foundation UK [SP/10/10/28431, PG/12/27/29489]; European Molecular Biology Laboratory; MRC UK; Wellcome Trust UK [087183/Z/08/Z, 092854/Z/10/Z, WT095908]; Fondation Leducq; Tanoto Foundation; Goh Foundation; Academy of Medical Sciences; Arthritis Research UK; Heart Research UK; CORDA; National Medical Research Council (NMRC) Singapore; Rosetrees Trus; European Community's Seventh Framework Programme (FP7 [GEN2PHEN project]) [CardioNeT-ITN-289600, 200754]; National Human Genome Research Institute [U54 HG003067]; NIH [HL080494, 5-T32-GM007748-33]; Howard Hughes Medical Institute; Australian National Health and Medical Research Council; NHLBI [N01-HC-25195, 6R01-NS 17950, N01-HC-95170, N01-HC-95171, N01-HC-95172, HL-102924]; National Institute for Minority Health and Health Disparities; National Institute of Biomedical Imaging and Bioengineering; U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221] FX The research was supported by the NIHR Biomedical Research Unit in Cardiovascular Disease at Royal Brompton & Harefield NHS Foundation Trust and Imperial College London, NIHR Imperial Biomedical Research Centre, British Heart Foundation UK (SP/10/10/28431, PG/12/27/29489), European Molecular Biology Laboratory, MRC UK, Wellcome Trust UK (087183/Z/08/Z, 092854/Z/10/Z, WT095908), Fondation Leducq, Tanoto Foundation, Goh Foundation, Academy of Medical Sciences, Arthritis Research UK, Heart Research UK, CORDA, National Medical Research Council (NMRC) Singapore, Rosetrees Trust, European Community's Seventh Framework Programme (FP7) [CardioNeT-ITN-289600; 200754 - the GEN2PHEN project], National Human Genome Research Institute (U54 HG003067), NIH (HL080494, 5-T32-GM007748-33), Howard Hughes Medical Institute, and the Australian National Health and Medical Research Council. The FHS was supported by the NHLBI (N01-HC-25195, 6R01-NS 17950), and genotyping services from Affymetrix Inc. (N02-HL-6-4278). The JHS is supported by NHLBI (N01-HC-95170, N01-HC-95171, N01-HC-95172), the National Institute for Minority Health and Health Disparities, and the National Institute of Biomedical Imaging and Bioengineering. The WHI Sequencing Project is supported by NHLBI (HL-102924), NIH, and U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. This publication reflects only the author's views, and the funders are not liable for any use that may be made of the information contained herein. NR 67 TC 42 Z9 43 U1 5 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 14 PY 2015 VL 7 IS 270 AR 270ra6 DI 10.1126/scitranslmed.3010134 PG 14 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AZ6TN UT WOS:000348353400004 PM 25589632 ER PT J AU Feng, AL You, ML Tian, LM Singamaneni, S Liu, M Duan, ZF Lu, TJ Xu, F Lin, M AF Feng, Ai Ling You, Min Li Tian, Limei Singamaneni, Srikanth Liu, Ming Duan, Zhenfeng Lu, Tian Jian Xu, Feng Lin, Min TI Distance-Dependent Plasmon-Enhanced Fluorescence of Upconversion Nanoparticles using Polyelectrolyte Multilayers as Tunable Spacers SO SCIENTIFIC REPORTS LA English DT Article ID CORE-SHELL NANOPARTICLES; BIOMEDICAL APPLICATIONS; MOLECULAR FLUORESCENCE; GOLD NANOPARTICLES; QUANTUM DOTS; IN-VIVO; LUMINESCENCE; NANOCRYSTALS; RESONANCE; EMISSION AB Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted widespread interests in bioapplications due to their unique optical properties by converting near infrared excitation to visible emission. However, relatively low quantum yield prompts a need for developing methods for fluorescence enhancement. Plasmon nanostructures are known to efficiently enhance fluorescence of the surrounding fluorophores by acting as nanoantennae to focus electric field into nano-volume. Here, we reported a novel plasmon-enhanced fluorescence system in which the distance between UCNPs and nanoantennae (gold nanorods, AuNRs) was precisely tuned by using layer-by-layer assembled polyelectrolyte multilayers as spacers. By modulating the aspect ratio of AuNRs, localized surface plasmon resonance (LSPR) wavelength at 980 nm was obtained, matching the native excitation of UCNPs resulting in maximum enhancement of 22.6-fold with 8 nm spacer thickness. These findings provide a unique platform for exploring hybrid nanostructures composed of UCNPs and plasmonic nanostructures in bioimaging applications. C1 [Feng, Ai Ling; You, Min Li; Xu, Feng; Lin, Min] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710049, Peoples R China. [Feng, Ai Ling; You, Min Li; Lu, Tian Jian; Xu, Feng; Lin, Min] Xi An Jiao Tong Univ, Bioinspired Engn & Biomech Ctr, Xian 710049, Peoples R China. [Tian, Limei; Singamaneni, Srikanth] Washington Univ, Inst Mat Sci & Engn, Dept Mech Engn & Mat Sci, St Louis, MO 63130 USA. [Liu, Ming] Xi An Jiao Tong Univ, Minist Educ, Elect Mat Res Lab, Xian 710049, Peoples R China. [Liu, Ming] Xi An Jiao Tong Univ, Int Ctr Dielect Res, Xian 710049, Peoples R China. [Duan, Zhenfeng; Lin, Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Lin, M (reprint author), Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710049, Peoples R China. EM minlin@mail.xjtu.edu.cn RI Xu, Feng/C-7430-2011; Lu, Tian Jian/E-6063-2016; Liu, Ming/B-4143-2009; Xu, Feng/H-4468-2011 OI Liu, Ming/0000-0002-6310-948X; Xu, Feng/0000-0003-4351-0222 FU National Natural Science Foundation of China [11120101002]; International Science & Technology Cooperation Program of China [2013DFG02930]; National Key Scientific Apparatus Development of Special Item [2013YQ190467]; Natural Science Basic Research Plan in Shaanxi Province of China [2014JQ6199]; Fundamental Research Funds for the Central Universities [2012jdhz46]; China Scholarship of Council; China Young 1000-Talent Program; Program for New Century Excellent Talents in University FX This work was financially supported by the National Natural Science Foundation of China (11120101002), International Science & Technology Cooperation Program of China (2013DFG02930), National Key Scientific Apparatus Development of Special Item (2013YQ190467), Natural Science Basic Research Plan in Shaanxi Province of China (2014JQ6199), the Fundamental Research Funds for the Central Universities (2012jdhz46). M.L. is supported by scholarship from the China Scholarship of Council. Feng Xu was also partially supported by the China Young 1000-Talent Program and the Program for New Century Excellent Talents in University. The SEM and TEM work was done at International Center for Dielectric Research (ICDR), Xi'an Jiaotong University, Xi'an, China. The authors also thank Ms. Dai Yan Zhu, Ms. Lu Lu and Mr. Ma Chuan Sheng for their help in using SEM and TEM. NR 50 TC 35 Z9 35 U1 23 U2 171 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 14 PY 2015 VL 5 AR 7779 DI 10.1038/srep07779 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY8ZM UT WOS:000347839200009 PM 25586238 ER PT J AU Wheeler, AL Tien, PC Grunfeld, C Schafer, AL AF Wheeler, Amber L. Tien, Phyllis C. Grunfeld, Carl Schafer, Anne L. TI Teriparatide treatment of osteoporosis in an HIV-infected man: a case report and literature review SO AIDS LA English DT Letter ID BONE; THERAPY; MEN C1 Univ Calif San Francisco, Dept Med, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Wheeler, AL (reprint author), Vet Affairs Med Ctr, Metab Sect, 111F,4150 Clement St, San Francisco, CA 94121 USA. EM amber.wheeler@ucsf.edu OI Wheeler, Amber/0000-0002-9926-1301 FU CSRD VA [IK2 CX000549]; NCATS NIH HHS [KL2TR000143, KL2 TR000143]; NIAID NIH HHS [K24 AI108516]; NICHD NIH HHS [5K12HD052163-15, K12 HD052163]; NIDDK NIH HHS [T32 DK007418] NR 6 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 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 14 PY 2015 VL 29 IS 2 BP 245 EP 246 DI 10.1097/QAD.0000000000000529 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AX8HE UT WOS:000347149900014 PM 25532609 ER PT J AU Daskalakis, NP Yehuda, R AF Daskalakis, Nikolaos P. Yehuda, Rachel TI Early maternal influences on stress circuitry: implications for resilience and susceptibility to physical and mental disorders SO FRONTIERS IN ENDOCRINOLOGY LA English DT Editorial Material DE early life stress; HPA axis; vulnerability; resilience; maternal ID HOLOCAUST SURVIVORS; PTSD; EXPOSURE; TRAUMA C1 [Daskalakis, Nikolaos P.; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Traumat Stress Studies Div, Dept Psychiat, New York, NY 10029 USA. [Daskalakis, Nikolaos P.; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr, Bronx, NY USA. [Daskalakis, Nikolaos P.] Icahn Sch Med Mt Sinai, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY 10029 USA. [Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. RP Daskalakis, NP (reprint author), Icahn Sch Med Mt Sinai, Traumat Stress Studies Div, Dept Psychiat, New York, NY 10029 USA.; Daskalakis, NP (reprint author), James J Peters Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr, Bronx, NY USA.; Daskalakis, NP (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY 10029 USA. EM nikolaos.daskalakis@mssm.edu OI Daskalakis, Nikolaos/0000-0003-1660-9112 NR 22 TC 1 Z9 1 U1 2 U2 3 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2392 J9 FRONT ENDOCRINOL JI Front. Endocrinol. PD JAN 14 PY 2015 VL 5 AR 244 DI 10.3389/fendo.2014.00244 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP3KL UT WOS:000378392100001 ER PT J AU Langer, R Weissleder, R AF Langer, Robert Weissleder, Ralph TI Nanotechnology SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Langer, Robert] MIT, Cambridge, MA 02139 USA. [Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Langer, R (reprint author), MIT, Langer Res Lab, 500 Main St,Room 76-661, Cambridge, MA 02139 USA. EM rlanger@mit.edu NR 6 TC 21 Z9 21 U1 5 U2 36 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 13 PY 2015 VL 313 IS 2 BP 135 EP 136 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AY6MC UT WOS:000347679300008 PM 25585320 ER PT J AU Teodorescu, M Barnet, JH Hagen, EW Palta, M Young, TB Peppard, PE AF Teodorescu, Mihaela Barnet, Jodi H. Hagen, Erika W. Palta, Mari Young, Terry B. Peppard, Paul E. TI Association Between Asthma and Risk of Developing Obstructive Sleep Apnea SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID UPPER AIRWAY; GASTROESOPHAGEAL-REFLUX; SYSTEMIC INFLAMMATION; INCREASED PREVALENCE; DAYTIME SLEEPINESS; SELF-REPORT; ADULTS; POPULATION; STEROIDS; DISEASE AB IMPORTANCE Obstructive sleep apnea (OSA) is more common among patients with asthma; whether asthma is associated with the development of OSA is unknown. OBJECTIVE To examine the prospective relationship of asthma with incident OSA. DESIGN, SETTING, AND PARTICIPANTS Population-based prospective epidemiologic study (the Wisconsin Sleep Cohort Study) beginning in 1988. Adult participants were recruited from a random sample of Wisconsin state employees to attend overnight polysomnography studies at 4-year intervals. Asthma and covariate information were assessed during polysomnography studies through March 2013. Eligible participants were identified as free of OSA (apnea-hypopnea index [AHI] of <5 events/h and not treated) by 2 baseline polysomnography studies. There were 1105 4-year follow-up intervals provided by 547 participants (52% women; mean [SD] baseline age, 50 [8] years). EXPOSURES Questionnaire-assessed presence and duration of self-reported physician-diagnosed asthma. MAIN OUTCOMES AND MEASURES The associations of presence and duration of asthma with 4-year incidences of both OSA (AHI of >= 5 or positive airway pressure treatment) and OSA concomitant with habitual daytime sleepiness were estimated using repeated-measures Poisson regression, adjusting for confounders. RESULTS Twenty-two of 81 participants (27%[95% CI, 17%-37%]) with asthma experienced incident OSA over their first observed 4-year follow-up interval compared with 75 of 466 participants (16%[95% CI, 13%-19%]) without asthma. Using all 4-year intervals, participants with asthma experienced 45 cases of incident OSA during 167 4-year intervals (27%[95% CI, 20%-34%]) and participants without asthma experienced 160 cases of incident OSA during 938 4-year intervals (17%[95% CI, 15%-19%]); the corresponding adjusted relative risk (RR) was 1.39 (95% CI, 1.06-1.82), controlling for sex, age, baseline and change in body mass index, and other factors. Asthma was also associated with new-onset OSA with habitual sleepiness (RR, 2.72 [95% CI, 1.26-5.89], P = .045). Asthma duration was related to both incident OSA (RR, 1.07 per 5-year increment in asthma duration [95% CI, 1.02-1.13], P = .01) and incident OSA with habitual sleepiness (RR, 1.18 [95% CI, 1.07-1.31], P = .02). CONCLUSIONS AND RELEVANCE Asthma was associated with an increased risk of new-onset OSA. Studies investigating the mechanisms underlying this association and the value of periodic OSA evaluation in patients with asthma are warranted. C1 [Teodorescu, Mihaela] William S Middleton Mem Vet Adm Med Ctr, James B Skatrud Pulm Sleep Res Lab, Madison, WI USA. [Teodorescu, Mihaela] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. [Teodorescu, Mihaela] Univ Wisconsin, Sch Med & Publ Hlth, Ctr Sleep Med & Sleep Res, Madison, WI 53792 USA. [Barnet, Jodi H.; Hagen, Erika W.; Palta, Mari; Young, Terry B.; Peppard, Paul E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53792 USA. RP Teodorescu, M (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, K4-910 CSC 9988,600 Highland Ave, Madison, WI 53792 USA. EM mt3@medicine.wisc.edu FU National Heart, Lung, and Blood Institute [R01HL62252]; National Institute on Aging [R01AG036838]; National Center for Research Resources at the National Institutes of Health (NIH) [1UL1RR025011] FX This work was funded by the National Heart, Lung, and Blood Institute (R01HL62252), National Institute on Aging (R01AG036838), and the National Center for Research Resources (1UL1RR025011) at the National Institutes of Health (NIH); additional resources were from the William S. Middleton Memorial VA Hospital, Madison. This work was performed at the University of Wisconsin and William S. Middleton Memorial VA Hospital, Madison. NR 34 TC 30 Z9 31 U1 3 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 13 PY 2015 VL 313 IS 2 BP 156 EP 164 DI 10.1001/jama.2014.17822 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AY6MC UT WOS:000347679300015 PM 25585327 ER PT J AU Rosenquist, JN Lehrer, SF O'Malley, AJ Zaslavsky, AM Smoller, JW Christakis, NA AF Rosenquist, James Niels Lehrer, Steven F. O'Malley, A. James Zaslavsky, Alan M. Smoller, Jordan W. Christakis, Nicholas A. TI Cohort of birth modifies the association between FTO genotype and BMI SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE population genetics; obesity; birth cohort ID BODY-MASS INDEX; BY-ENVIRONMENT INTERACTION; GENOME-WIDE ASSOCIATION; GENETIC ASSOCIATIONS; ADULT OBESITY; ENERGY-INTAKE; CHILDREN; INTELLIGENCE; CHILDHOOD; VARIANT AB A substantial body of research has explored the relative roles of genetic and environmental factors on phenotype expression in humans. Recent research has also sought to identify gene-environment (or g-by-e) interactions, with mixed success. One potential reason for these mixed results may relate to the fact that genetic effects might be modified by changes in the environment over time. For example, the noted rise of obesity in the United States in the latter part of the 20th century might reflect an interaction between genetic variation and changing environmental conditions that together affect the penetrance of genetic influences. To evaluate this hypothesis, we use longitudinal data from the Framingham Heart Study collected over 30 y from a geographically relatively localized sample to test whether the well-documented association between the rs993609 variant of the FTO (fat mass and obesity associated) gene and body mass index (BMI) varies across birth cohorts, time period, and the lifecycle. Such cohort and period effects integrate many potential environmental factors, and this gene-by-environment analysis examines interactions with both time-varying contemporaneous and historical environmental influences. Using constrained linear age-period-cohort models that include family controls, we find that there is a robust relationship between birth cohort and the genotype-phenotype correlation between the FTO risk allele and BMI, with an observed inflection point for those born after 1942. These results suggest genetic influences on complex traits like obesity can vary over time, presumably because of global environmental changes that modify allelic penetrance. C1 [Rosenquist, James Niels] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lehrer, Steven F.] Queens Univ, Sch Policy Studies, Kingston, ON K7L 3N6, Canada. [Lehrer, Steven F.] Queens Univ, Dept Econ, Kingston, ON K7L 3N6, Canada. [Lehrer, Steven F.] Natl Bur Econ Res USA, Cambridge, MA 02138 USA. [O'Malley, A. James] Dartmouth Coll, Geisel Sch Med, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH 03755 USA. [Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Christakis, Nicholas A.] Yale Univ, Dept Sociol, New Haven, CT 06520 USA. [Christakis, Nicholas A.] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Christakis, Nicholas A.] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA. [Christakis, Nicholas A.] Yale Univ, Yale Inst Network Sci, New Haven, CT 06520 USA. RP Rosenquist, JN (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM JRosenquist@partners.org FU National Institute on Aging [P01-AG031093]; Social Sciences and Humanities Research Council; National Heart, Lung, and Blood Institute (NHLBI) [N02-HL-64278]; NHLBI; Boston University [N01-HC-25195]; NIH dbGap [780] FX We thank David Cutler, Eliana Hechter, Heidi Williams, and two anonymous reviewers for helpful comments. We also thank Peter Treut and Emily Hau for assistance with data visualizations. This work was supported by Grant P01-AG031093 from the National Institute on Aging and the Social Sciences and Humanities Research Council (to S. F. L.). Funding for SHARe Affymetrix genotyping was provided by National Heart, Lung, and Blood Institute (NHLBI) Contract N02-HL-64278. The Framingham Heart Study is conducted and supported by the NHLBI in collaboration with Boston University (Contract N01-HC-25195). Data were downloaded from NIH dbGap, Project 780, with accession phs000153. SocialNetwork. v6.p5.c1. GRU and general research use phs000153. SocialNetwork. v6.p5.c2.NPU. NR 48 TC 17 Z9 17 U1 1 U2 20 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 13 PY 2015 VL 112 IS 2 BP 354 EP 359 DI 10.1073/pnas.1411893111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY7HS UT WOS:000347732300035 PM 25548176 ER PT J AU Cipolletta, D Cohen, P Spiegelman, BM Benoist, C Mathis, D AF Cipolletta, Daniela Cohen, Paul Spiegelman, Bruce M. Benoist, Christophe Mathis, Diane TI Appearance and disappearance of the mRNA signature characteristic of T-reg cells in visceral adipose tissue: Age, diet, and PPAR gamma effects SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE obesity; inflammation; type 2 diabetes; regulatory T cell; Foxp3 ID SYSTEM; PHOSPHORYLATION; RETROVIRUSES; MICE; FAT AB A unique population of Foxp3(+)CD4(+) regulatory T (T-reg) cells resides in visceral adipose tissue (VAT) of lean mice, especially in the epididymal fat depot. VAT T-regs are unusual in their very high representation within the CD4(+) T-cell compartment, their transcriptome, and their repertoire of antigen-specific T-cell receptors. They are important regulators of local and systemic inflammation and metabolism. The overall goal of this study was to learn how the VAT T-reg transcriptome adapts to different stimuli; in particular, its response to aging in lean mice, to metabolic perturbations associated with obesity, and to certain signaling events routed through PPAR gamma, the "master-regulator" of adipocyte differentiation. We show that the VAT T-reg signature is imposed early in life, well before age-dependent expansion of the adipose-tissue Treg population. VAT T-regs in obese mice lose the signature typical of lean individuals but gain an additional set of over-and underrepresented transcripts. This obese mouse VAT T-reg signature depends on phosphorylation of the serine residue at position 273 of PPAR gamma, in striking parallel to a pathway recently elucidated in adipocytes. These findings are important to consider in designing drugs to target type 2 diabetes and other features of the "metabolic syndrome." C1 [Cipolletta, Daniela; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. [Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. [Benoist, Christophe; Mathis, Diane] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. EM cbdm@hms.harvard.edu FU NIH [R01 DK092541]; Ellison Foundation (Boston); JPB Foundation; Joslin Diabetes Center [P30DK36836] FX We thank V. Babatunde for help with cloning, K. Hattori for assistance with mouse husbandry, J. LaVecchio and G. Buruzala for flow-cytometry, J. Ericson and K. Leatherbee for RNA processing, S. Davis for help with the microarray analysis, and Dr. M. T. Wilson for discussions. This work was supported by grants from the NIH (R01 DK092541), the Ellison Foundation (Boston), and the JPB Foundation (to D.M. and B.M.S.), and by the core facilities of the Joslin Diabetes Center (P30DK36836). NR 14 TC 15 Z9 15 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 13 PY 2015 VL 112 IS 2 BP 482 EP 487 DI 10.1073/pnas.1423486112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY7HS UT WOS:000347732300057 PM 25550516 ER PT J AU Leavenworth, JW Verbinnen, B Wang, Q Shen, E Cantor, H AF Leavenworth, Jianmei W. Verbinnen, Bert Wang, Qin Shen, Erxia Cantor, Harvey TI Intracellular osteopontin regulates homeostasis and function of natural killer cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cellular maintenance; contraction; long-lived cell; memory cell; T-box transcription factor ID T-BET; NK-CELLS; PERIPHERAL HOMEOSTASIS; ADAPTIVE IMMUNITY; DENDRITIC CELLS; MEMORY; MATURATION; SURVIVAL; IL-15; CYTOMEGALOVIRUS AB Natural killer (NK) cells play an essential role in the immune response to infection and cancer. After infection or during homeostatic expansion NK cells express a developmental program that includes a contraction phase followed by the formation of long-lived mature memory-like cells. Although this NK cell response pattern is well established, the underlying mechanisms that ensure efficient transition to long-lived NK cells remain largely undefined. Here we report that deficient expression of intracellular osteopontin (OPN-i) by NK cells results in defective responses to IL-15 associated with a substantial increase in the NK cell contraction phase of homeostatic expansion, defective expression of the Eomes transcription factor, and diminished responses to metastatic tumors. The OPN-i-deficient phenotype is accompanied by increased NK cell apoptosis, impaired transition from immature to mature NK cells, and diminished ability to develop memory-like NK cells that respond to mouse cytomegalovirus. Gene pathway analysis of OPN-i-deficient NK cells suggests that the mechanistic target of rapamycin pathway may connect OPN-i to Eomes and T-bet expression by mature NK cells following up-regulation of OPN-i after IL-15 stimulation. Identification of OPN-i as an essential molecular component for maintenance of functional NK cell expansion provides insight into the NK cell response and may provide the basis for improved approaches to immunotherapy for infectious disease and cancer. C1 [Leavenworth, Jianmei W.; Verbinnen, Bert; Wang, Qin; Shen, Erxia; Cantor, Harvey] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Leavenworth, Jianmei W.; Verbinnen, Bert; Wang, Qin; Shen, Erxia; Cantor, Harvey] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leavenworth, Jianmei W.; Cantor, Harvey] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [Wang, Qin] Soochow Univ, Coll Med, Dept Immunol, Suzhou 215123, Jiangsu, Peoples R China. [Shen, Erxia] Guangzhou Med Univ, Sch Basic Sci, Guangzhou Hoffmann Inst Immunol, Dept Pathogen Biol & Immunol, Guangzhou 510182, Guangdong, Peoples R China. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu FU National Institutes of Health [AI48125]; Benacerraf Fellowship; National Research Service Award Fellowship [T32 CA070083]; Belgian-American Educational Foundation FX We thank Yue Shao (Dana-Farber Cancer Institute Microarray Facility) for microarray analysis and A. Angel for manuscript and figure preparation. This work was supported in part by National Institutes of Health Research Grant AI48125, a gift from The LeRoy Schecter Research Foundation (to H.C.), the Benacerraf Fellowship and National Research Service Award Fellowship (T32 CA070083) (to J.W.L.), and a Belgian-American Educational Foundation Fellowship (to B.V.). NR 39 TC 4 Z9 4 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 13 PY 2015 VL 112 IS 2 BP 494 EP 499 DI 10.1073/pnas.1423011112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY7HS UT WOS:000347732300059 PM 25550515 ER PT J AU Godec, J Cowley, GS Barnitz, RA Root, DE Sharpe, AH Haining, WN AF Godec, Jernej Cowley, Glenn S. Barnitz, R. Anthony Root, David E. Sharpe, Arlene H. Haining, W. Nicholas TI Inducible RNAi in vivo reveals that the transcription factor BATF is required to initiate but not maintain CD8(+) T-cell effector differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD8 T cell; RNAi; transcription factor; BATF ID MEMORY; RESPONSES; NETWORK; ANTIGEN; DISCOVERY; MICE AB The differentiation of effector CD8(+) T cells is critical for the development of protective responses to pathogens and for effective vaccines. In the first few hours after activation, naive CD8(+) T cells initiate a transcriptional program that leads to the formation of effector and memory T cells, but the regulation of this process is poorly understood. Investigating the role of specific transcription factors (TFs) in determining CD8(+) effector T-cell fate by gene knockdown with RNAi is challenging because naive T cells are refractory to transduction with viral vectors without extensive ex vivo stimulation, which obscures the earliest events in effector differentiation. To overcome this obstacle, we developed a novel strategy to test the function of genes in naive CD8(+) T cells in vivo by creating bone marrow chimera from hematopoietic progenitors transduced with an inducible shRNA construct. Following hematopoietic reconstitution, this approach allowed inducible in vivo gene knockdown in any cell type that developed from this transduced progenitor pool. We demonstrated that lentivirus-transduced progenitor cells could reconstitute normal hematopoiesis and develop into naive CD8(+) T cells that were indistinguishable from wild-type naive T cells. This experimental system enabled induction of efficient gene knockdown in vivo without subsequent manipulation. We applied this strategy to show that the TF BATF is essential for initial commitment of naive CD8(+) T cells to effector development but becomes dispensable by 72h. This approach makes possible the study of gene function in vivo in unperturbed cells of hematopoietic origin that are refractory to viral transduction. C1 [Godec, Jernej; Barnitz, R. Anthony; Haining, W. Nicholas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Godec, Jernej; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Godec, Jernej; Sharpe, Arlene H.] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. [Godec, Jernej; Sharpe, Arlene H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cowley, Glenn S.; Root, David E.; Sharpe, Arlene H.; Haining, W. Nicholas] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Sharpe, Arlene H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Haining, WN (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM arlene_sharpe@hms.harvard.edu; nicholas_haining@dfci.harvard.edu OI Barnitz, Tony/0000-0002-9634-4558 FU National Institutes of Health [AI091493, AI057266, AI082630, AI38310]; Cancer Research Institute Predoctoral Emphasis Pathway in Tumor Immunology FX We thank John G. Doench, E. John Wherry, and the members of the W.N.H. and A.H.S. laboratories for meaningful discussions. This work was supported by the National Institutes of Health Grants AI091493, AI057266, AI082630 (to W.N.H.), AI38310 (to A.H.S.), and Cancer Research Institute Predoctoral Emphasis Pathway in Tumor Immunology (J.G.). NR 23 TC 8 Z9 8 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 13 PY 2015 VL 112 IS 2 BP 512 EP 517 DI 10.1073/pnas.1413291112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY7HS UT WOS:000347732300062 PM 25548173 ER PT J AU Van Dort, CJ Zachs, DP Kenny, JD Zheng, S Goldblum, RR Gelwan, NA Ramos, DM Nolan, MA Wang, KR Weng, FJ Lin, YX Wilson, MA Brown, EN AF Van Dort, Christa J. Zachs, Daniel P. Kenny, Jonathan D. Zheng, Shu Goldblum, Rebecca R. Gelwan, Noah A. Ramos, Daniel M. Nolan, Michael A. Wang, Karen Weng, Feng-Ju Lin, Yingxi Wilson, Matthew A. Brown, Emery N. TI Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE rapid eye movement sleep; acetylcholine; optogenetics; mesopontine tegmentum; mouse ID LATERODORSAL TEGMENTAL NUCLEUS; FREELY MOVING CATS; BRAIN-STEM; PONTOMESENCEPHALIC TEGMENTUM; PARADOXICAL SLEEP; GLUTAMATERGIC NEURONS; GABAERGIC NEURONS; WAKING CYCLE; IN-VITRO; RAT AB Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep. C1 [Van Dort, Christa J.; Zachs, Daniel P.; Kenny, Jonathan D.; Gelwan, Noah A.; Brown, Emery N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Van Dort, Christa J.; Zachs, Daniel P.; Kenny, Jonathan D.; Zheng, Shu; Goldblum, Rebecca R.; Gelwan, Noah A.; Ramos, Daniel M.; Nolan, Michael A.; Wang, Karen; Weng, Feng-Ju; Lin, Yingxi; Wilson, Matthew A.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Van Dort, Christa J.; Zachs, Daniel P.; Kenny, Jonathan D.; Goldblum, Rebecca R.; Gelwan, Noah A.; Ramos, Daniel M.; Nolan, Michael A.; Wang, Karen; Wilson, Matthew A.] MIT, Picower Inst Learning & Mem, Cambridge, MA 02139 USA. [Weng, Feng-Ju; Lin, Yingxi] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Goldblum, Rebecca R.; Nolan, Michael A.; Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Van Dort, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM vandortc@mit.edu; enb@neurostat.mit.edu OI Kenny, Jonathan/0000-0003-3745-3217 FU NIH [DP1-OD003646, TR01-GM104948, T32-HL07901]; Massachusetts General Hospital Executive Committee on Research Fellowship; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital FX This study was supported by NIH Grant DP1-OD003646 (to E.N.B.), NIH Grant TR01-GM104948 (to E.N.B. and M.A.W.), and NIH Grant T32-HL07901 (to C.J.V.); a Massachusetts General Hospital Executive Committee on Research Fellowship (to C.J.V.); and the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital. NR 41 TC 31 Z9 32 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 13 PY 2015 VL 112 IS 2 BP 584 EP 589 DI 10.1073/pnas.1423136112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY7HS UT WOS:000347732300074 PM 25548191 ER PT J AU Maldonado, RA LaMothe, RA Ferrari, JD Zhang, AH Rossi, RJ Kolte, PN Griset, AP O'Neil, C Altreuter, DH Browning, E Johnston, L Farokhzad, OC Langer, R Scott, DW von Andrian, UH Kishimoto, TK AF Maldonado, Roberto A. LaMothe, Robert A. Ferrari, Joseph D. Zhang, Ai-Hong Rossi, Robert J. Kolte, Pallavi N. Griset, Aaron P. O'Neil, Conlin Altreuter, David H. Browning, Erica Johnston, Lloyd Farokhzad, Omid C. Langer, Robert Scott, David W. von Andrian, Ulrich H. Kishimoto, Takashi Kei TI Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nanoparticles; immune tolerance; rapamycin; immunotherapy; anti-drug antibodies ID TOLEROGENIC DENDRITIC CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ENZYME-REPLACEMENT THERAPY; SYNGENEIC LYMPHOID-CELLS; FACTOR-VIII; IMMUNE MODULATION; HEMOPHILIA-A; RISK-FACTORS; RESPONSES; DISEASE AB Current treatments to control pathological or unwanted immune responses often use broadly immunosuppressive drugs. New approaches to induce antigen-specific immunological tolerance that control both cellular and humoral immune responses are desirable. Here we describe the use of synthetic, biodegradable nanoparticles carrying either protein or peptide antigens and a tolerogenic immunomodulator, rapamycin, to induce durable and antigen-specific immune tolerance, even in the presence of potent Toll-like receptor agonists. Treatment with tolerogenic nanoparticles results in the inhibition of CD4+ and CD8+ T-cell activation, an increase in regulatory cells, durable B-cell tolerance resistant to multiple immunogenic challenges, and the inhibition of antigen-specific hypersensitivity reactions, relapsing experimental autoimmune encephalomyelitis, and antibody responses against coagulation factor VIII in hemophilia A mice, even in animals previously sensitized to antigen. Only encapsulated rapamycin, not the free form, could induce immunological tolerance. Tolerogenic nanoparticle therapy represents a potential novel approach for the treatment of allergies, autoimmune diseases, and prevention of antidrug antibodies against biologic therapies. C1 [Maldonado, Roberto A.; LaMothe, Robert A.; Ferrari, Joseph D.; Kolte, Pallavi N.; Griset, Aaron P.; O'Neil, Conlin; Altreuter, David H.; Browning, Erica; Johnston, Lloyd; Kishimoto, Takashi Kei] Selecta Biosci Inc, Watertown, MA 02472 USA. [Zhang, Ai-Hong; Rossi, Robert J.; Scott, David W.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Farokhzad, Omid C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol,Lab Nanomed & Biomat, Boston, MA 02115 USA. [Farokhzad, Omid C.] King Abdulaziz Univ, Jeddah 22254, Saudi Arabia. [Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Langer, Robert] David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [von Andrian, Ulrich H.] MIT & Harvard, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. RP Kishimoto, TK (reprint author), Selecta Biosci Inc, Watertown, MA 02472 USA. EM kkishimoto@selectabio.com FU Juvenile Diabetes Research Foundation FX The authors gratefully acknowledge the excellent support of Aditi Chalishazar, Dr. Lynelle Pittet, and the ELISA team for ELISA analyses and Dr. Fen-ni Fu, Dr. William Kuhlman, Dr. Victor Chan, Ray Damien, and Dr. Nelly Viseux for analytical characterization of nanoparticles. We thank Dr. Suzana Marusic for support with the EAE studies. This work was partially funded by a grant from the Juvenile Diabetes Research Foundation. NR 47 TC 47 Z9 47 U1 16 U2 78 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 13 PY 2015 VL 112 IS 2 BP E156 EP E165 DI 10.1073/pnas.1408686111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY7HS UT WOS:000347732300010 PM 25548186 ER PT J AU Lopez, MF Krastins, B Sarracino, DA Byram, G Vogelsang, MS Prakash, A Peterman, S Ahmad, S Vadali, G Deng, WJ Inglessis, I Wickham, T Feeney, K Dec, GW Palacios, I Buonanno, FS Lo, EH Ning, MM AF Lopez, Mary F. Krastins, Bryan Sarracino, David A. Byram, Gregory Vogelsang, Maryann S. Prakash, Amol Peterman, Scott Ahmad, Shadab Vadali, Gouri Deng, Wenjun Inglessis, Ignacio Wickham, Tom Feeney, Kathleen Dec, G. William Palacios, Igor Buonanno, Ferdinando S. Lo, Eng H. Ning, MingMing TI Proteomic signatures of serum albumin-bound proteins from stroke patients with and without endovascular closure of PFO are significantly different and suggest a novel mechanism for cholesterol efflux SO CLINICAL PROTEOMICS LA English DT Article DE Biomarker; Discovery; Stroke; Cerebrovascular disease; Ischemic stroke; Patent foramen ovale; PFO; Mass spectrometry; Proteomics; Albumin ID HIGH-DENSITY-LIPOPROTEIN; PATENT FORAMEN OVALE; MASS-SPECTROMETRIC IMMUNOASSAY; CARDIOVASCULAR-DISEASE; HIGH-THROUGHPUT; HUMAN-PLASMA; CELLS; CANCER; OPPORTUNITIES; METABOLISM AB Background: The anatomy of PFO suggests that it can allow thrombi and potentially harmful circulatory factors to travel directly from the venous to the arterial circulation - altering circulatory phenotype. Our previous publication using high-resolution LC-MS/MS to profile protein and peptide expression patterns in plasma showed that albumin was relatively increased in donor samples from PFO-related than other types of ischemic strokes. Since albumin binds a host of molecules and acts as a carrier for lipoproteins, small molecules and drugs, we decided to investigate the albumin-bound proteins (in a similar sample cohort) in an effort to unravel biological changes and potentially discover biomarkers related to PFO-related stroke and PFO endovascular closure. Methods: The method used in this study combined albumin immuno-enrichment with high resolution LC-MS in order to specifically capture and quantify the albumin-bound proteins. Subsequently, we measured cholesterol and HDL in a larger, separate cohort of PFO stroke patients, pre and post closure. Results: The results demonstrated that a number of proteins were specifically associated with albumin in samples with and without endovascular closure of the PFO, and that the protein profiles were very different. Eight proteins, typically associated with HDL were common to both sample sets and quantitatively differently abundant. Pathway analysis of the MS results suggested that enhanced cholesterol efflux and reduced lipid oxidation were associated with PFO closure. Measurement of total cholesterol and HDL in a larger cohort of PFO closure samples using a colorimetric assay was consistent with the proteomic predictions. Conclusions: The collective data presented in this study demonstrate that analysis of albumin-bound proteins could provide a valuable tool for biomarker discovery on the effects of PFO endovascular closure. In addition, the results suggest that PFO endovascular closure can potentially have effects on HDL, cholesterol and albumin-bound ApoA-I abundance, therefore possibly providing benefits in cardioprotective functions. C1 [Lopez, Mary F.; Krastins, Bryan; Sarracino, David A.; Byram, Gregory; Vogelsang, Maryann S.; Prakash, Amol; Peterman, Scott; Ahmad, Shadab; Vadali, Gouri] Thermo Sci BRIMS, 790 Mem Dr, Cambridge, MA 02139 USA. [Deng, Wenjun; Inglessis, Ignacio; Wickham, Tom; Feeney, Kathleen; Dec, G. William; Palacios, Igor; Buonanno, Ferdinando S.; Lo, Eng H.; Ning, MingMing] Harvard Univ, Sch Med, Dept Neurol, Clin Prote Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Deng, Wenjun; Inglessis, Ignacio; Wickham, Tom; Feeney, Kathleen; Dec, G. William; Palacios, Igor; Buonanno, Ferdinando S.; Lo, Eng H.; Ning, MingMing] Harvard Univ, Sch Med, Dept Neurol, Cardioneurol Clin,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Lopez, MF (reprint author), Thermo Sci BRIMS, 790 Mem Dr, Cambridge, MA 02139 USA. EM mary.lopez@thermofisher.com NR 40 TC 8 Z9 9 U1 5 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1542-6416 EI 1559-0275 J9 CLIN PROTEOM JI Clin. Proteom. PD JAN 13 PY 2015 VL 12 AR 2 DI 10.1186/1559-0275-12-2 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA DF2WH UT WOS:000371204600002 PM 25678897 ER PT J AU Ahlfors, SP Jones, SR Ahveninen, J Hamalainen, MS Belliveau, JW Bar, M AF Ahlfors, Seppo P. Jones, Stephanie R. Ahveninen, Jyrki Haemaelaeinen, Matti S. Belliveau, John W. Bar, Moshe TI Direction of magnetoencephalography sources associated with feedback and feedforward contributions in a visual object recognition task SO NEUROSCIENCE LETTERS LA English DT Article DE Magnetoencephalography; Cerebral cortex; Current dipole; Top-down; Bottom-up ID PRIMARY SOMATOSENSORY CORTEX; TOP-DOWN FACILITATION; EXTRASTRIATE CORTEX; SOURCE LOCALIZATION; EVOKED-RESPONSES; MU RHYTHM; MEG; MODULATION; BRAIN; EEG AB Identifying inter-area communication in terms of the hierarchical organization of functional brain areas is of considerable interest in human neuroimaging. Previous studies have suggested that the direction of magneto- and electroencephalography (MEG, EEG) source currents depend on the layer-specific input patterns into a cortical area. We examined the direction in MEG source currents in a visual object recognition experiment in which there were specific expectations of activation in the fusiform region being driven by either feedforward or feedback inputs. The source for the early non-specific visual evoked response, presumably corresponding to feedforward driven activity, pointed outward, i.e., away from the white matter. In contrast, the source for the later, object-recognition related signals, expected to be driven by feedback inputs, pointed inward, toward the white matter. Associating specific features of the MEG/EEG source waveforms to feedforward and feedback inputs could provide unique information about the activation patterns within hierarchically organized cortical areas. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Ahlfors, Seppo P.; Jones, Stephanie R.; Ahveninen, Jyrki; Haemaelaeinen, Matti S.; Belliveau, John W.; Bar, Moshe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ahlfors, Seppo P.; Haemaelaeinen, Matti S.; Belliveau, John W.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02135 USA. [Jones, Stephanie R.] Brown Univ, Providence, RI 02912 USA. [Bar, Moshe] Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-52900 Ramat Gan, Israel. RP Ahlfors, SP (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM seppo@nmr.mgh.harvard.edu RI Ahlfors, Seppo/P-3644-2016 FU NIH [NS57500, NS37462, EY019477]; Israeli Center of Research Excellence in Cognitive Sciences ICORE [51/11]; National Center for Research Resources [P41EB015896] FX This work was supported by NIH grants NS57500 (SPA), NS37462 (JWB/SPA), EY019477 (MB), and The Israeli Center of Research Excellence in Cognitive Sciences ICORE grant No. 51/11 (MB). This work was supported in part by The National Center for Research Resources (P41EB015896). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 4 Z9 6 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 12 PY 2015 VL 585 BP 149 EP 154 DI 10.1016/j.neulet.2014.11.029 PG 6 WC Neurosciences SC Neurosciences & Neurology GA CA8TS UT WOS:000349194400029 PM 25445356 ER PT J AU Pfirschke, C Garris, C Pittet, MJ AF Pfirschke, Christina Garris, Christopher Pittet, Mikael J. TI Common TLR5 Mutations Control Cancer Progression SO CANCER CELL LA English DT Editorial Material ID T-CELL; MICROBIOTA; DEFENSE; TUMORS C1 [Pfirschke, Christina; Garris, Christopher; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Pfirschke, Christina; Garris, Christopher; Pittet, Mikael J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Pittet, MJ (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu NR 9 TC 4 Z9 4 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD JAN 12 PY 2015 VL 27 IS 1 BP 1 EP 3 DI 10.1016/j.ccell.2014.12.008 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AY9ZS UT WOS:000347906900001 PM 25584886 ER PT J AU Damsky, W Micevic, G Meeth, K Muthusamy, V Curley, DP Santhanakrishnan, M Erdelyi, I Platt, JT Huang, L Theodosakis, N Zaidi, MR Tighe, S Davies, MA Dankort, D McMahon, M Merlino, G Bardeesy, N Bosenberg, M AF Damsky, William Micevic, Goran Meeth, Katrina Muthusamy, Viswanathan Curley, David P. Santhanakrishnan, Manjula Erdelyi, Ildiko Platt, James T. Huang, Laura Theodosakis, Nicholas Zaidi, M. Raza Tighe, Scott Davies, Michael A. Dankort, David McMahon, Martin Merlino, Glenn Bardeesy, Nabeel Bosenberg, Marcus TI mTORC1 Activation Blocks Braf(V600E)-Induced Growth Arrest but Is Insufficient for Melanoma Formation SO CANCER CELL LA English DT Article ID ONCOGENE-INDUCED SENESCENCE; MALIGNANT MELANOMAS; CUTANEOUS MELANOMA; MELANOCYTIC TUMORS; MOUSE MODEL; COMPLEX 2; PTEN LOSS; EXPRESSION; CANCER; NEVI AB Braf(V600E) induces benign, growth-arrested melanocytic nevus development, but also drives melanoma formation. Cdkn2a loss in Braf(V600E) melanocytes in mice results in rare progression to melanoma, but only after stable growth arrest as nevi. Immediate progression to melanoma is prevented by upregulation of miR-99/100, which downregulates mTOR and IGF1R signaling. mTORC1 activation through Stk11 (Lkb1) loss abrogates growth arrest of Braf(V600E) melanocytic nevi, but is insufficient for complete progression to melanoma. Cdkn2a loss is associated with mTORC2 and Akt activation in human and murine melanocytic neoplasms. Simultaneous Cdkn2a and Lkb1 inactivation in Braf(V600E) melanocytes results in activation of both mTORC1 and mTORC2/Akt, inducing rapid melanoma formation in mice. In this model, activation of both mTORC1/2 is required for Braf-induced melanomagenesis. C1 [Damsky, William; Micevic, Goran; Platt, James T.; Huang, Laura; Bosenberg, Marcus] Yale Univ, Dept Dermatol, New Haven, CT 06510 USA. [Micevic, Goran; Meeth, Katrina; Theodosakis, Nicholas; Bosenberg, Marcus] Yale Univ, Dept Pathol, New Haven, CT 06510 USA. [Muthusamy, Viswanathan] Yale Univ, Dept Chem, New Haven, CT 06510 USA. [Curley, David P.] Brown Univ, Dept Emergency Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [Santhanakrishnan, Manjula] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. [Erdelyi, Ildiko] Yale Univ, Sch Med, Sect Comparat Med, New Haven, CT 06510 USA. [Zaidi, M. Raza] Temple Univ, Fels Inst Canc Res & Mol Biol, Sch Med, Philadelphia, PA 19140 USA. [Tighe, Scott] Univ Vermont, Coll Med, Vermont Canc Ctr, NextGen Sequencing Facil, Burlington, VT 05405 USA. [Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Dankort, David] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada. [McMahon, Martin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA. [McMahon, Martin] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA. [Merlino, Glenn] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Damsky, W (reprint author), Yale Univ, Dept Dermatol, New Haven, CT 06510 USA. EM william.damsky@gmail.com; marcus.bosenberg@yale.edu RI Zaidi, M. Raza/H-1386-2016; OI Zaidi, M. Raza/0000-0003-0480-3188; Dankort, David/0000-0002-5862-6829 FU National Cancer Institute [NCI] Cancer Center Support Grant [CCSG] [CA-16672]; NCI [R01 CA112054, P50 CA121974, P01 CA128814]; Hevery Foundation; Joanna M. Nicolay Melanoma Foundation; GlaxoSmithKline; Genentech; Merck; Myriad; AstraZeneca; Sanofi-Aventis FX The authors thank all members of the M.B. lab. We also thank Z. Zhao for FACS sort assistance, the Yale Dermatopathology lab for tissue processing, the University of Vermont Microarray Core Facility for assistance with microarray analyses, and the RPPA Core Facility at MD Anderson Cancer Center for the RPPA analyses (supported by National Cancer Institute [NCI] Cancer Center Support Grant [CCSG] CA-16672). Special thanks to R. Halaban for providing human melanoma cell lines and to D. Stern and his lab for the human melanoma RPPA analyses. This work was supported by grants from the NCI (R01 CA112054, P50 CA121974, and P01 CA128814) and the Hevery and Joanna M. Nicolay Melanoma Foundations. The results in part are based on data generated by the TCGA Research Network. M. A. D. has served on advisory boards for GlaxoSmithKline, Genentech, Novartis, and Sanofi-Aventis and has received research funding from GlaxoSmithKline, Genentech, Merck, Myriad, AstraZeneca, and Sanofi-Aventis. NR 51 TC 18 Z9 19 U1 4 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD JAN 12 PY 2015 VL 27 IS 1 BP 41 EP 56 DI 10.1016/j.ccell.2014.11.014 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AY9ZS UT WOS:000347906900009 PM 25584893 ER PT J AU Costa, C Ebi, H Martini, M Beausoleil, SA Faber, AC Jakubik, CT Huang, A Wang, YZ Nishtala, M Hall, B Rikova, K Zhao, JA Hirsch, E Benes, CH Engelman, JA AF Costa, Carlotta Ebi, Hiromichi Martini, Miriam Beausoleil, Sean A. Faber, Anthony C. Jakubik, Charles T. Huang, Alan Wang, Youzhen Nishtala, Madhuri Hall, Ben Rikova, Klarisa Zhao, Jean Hirsch, Emilio Benes, Cyril H. Engelman, Jeffrey A. TI Measurement of PIP3 Levels Reveals an Unexpected Role for p110 beta in Early Adaptive Responses to p110 alpha-Specific Inhibitors in Luminal Breast Cancer SO CANCER CELL LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; SELECTIVE INHIBITOR; PI3K INHIBITORS; CLINICAL-TRIALS; PROTEIN-KINASE; ACTIVATES AKT; MUTATIONS; PIK3CA; TRANSFORMATION; GROWTH AB BYL719, which selectively inhibits the alpha isoform of the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110a), is currently in clinical trials for the treatment of solid tumors, especially luminal breast cancers with PIK3CA mutations and/or HER2 amplification. This study reveals that, even among these sensitive cancers, the initial efficacy of p110 alpha inhibition is mitigated by rapid re-accumulation of the PI3K product PIP3 produced by the p110 beta isoform. Importantly, the reactivation of PI3K mediated by p110b does not invariably restore AKT phosphorylation, demonstrating the limitations of using phospho-AKT as a surrogate to measure PI3K activation. Consistently, we show that the addition of the p110 beta inhibitor to BYL719 prevents the PIP3 rebound and induces greater antitumor efficacy in HER2-amplified and PIK3CA mutant cancers. C1 [Costa, Carlotta; Ebi, Hiromichi; Faber, Anthony C.; Jakubik, Charles T.; Nishtala, Madhuri; Benes, Cyril H.; Engelman, Jeffrey A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Martini, Miriam; Hirsch, Emilio] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Mol Biotechnol Ctr, I-10126 Turin, Italy. [Beausoleil, Sean A.; Hall, Ben; Rikova, Klarisa] Cell Signaling Technol Inc, Danvers, MA 01923 USA. [Huang, Alan; Wang, Youzhen] Novartis Inst BioMed Res, Cambridge, MA 02139 USA. [Zhao, Jean] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Zhao, Jean] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. RP Engelman, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. EM jengelman@partners.org FU NIH [R01CA137008]; AIRC, Italy; Novartis Pharmaceuticals FX This study is supported by grants from the NIH R01CA137008 (to J.A.E.) and AIRC, Italy (to E.H.). We thank Targeting PI3K in Women's Cancers Stand Up to Cancer Dream Team for supplying GDC-0941. We thank Dr. Lucia Rameh for performing the PIP3 measurement using HPLC. We thank Drs. Rosen and Schwartz for critical reading of this manuscript. A.H. and Y.W. are employees and shareholders of Novartis Pharmaceuticals. C.H.B. received research support from Novartis Pharmaceuticals. J.A.E. is a consultant for Novartis and receives research support from Novartis Pharmaceuticals. NR 38 TC 40 Z9 40 U1 3 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD JAN 12 PY 2015 VL 27 IS 1 BP 97 EP 108 DI 10.1016/j.ccell.2014.11.007 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AY9ZS UT WOS:000347906900013 PM 25544637 ER PT J AU Edelman, MJ Tan, MT Fidler, MJ Sanborn, RE Otterson, G Sequist, LV Evans, TL Schneider, BJ Keresztes, R Rogers, JS de Mayolo, JA Feliciano, J Yang, Y Medeiros, M Zaknoen, SL AF Edelman, Martin J. Tan, Ming T. Fidler, Mary J. Sanborn, Rachel E. Otterson, Greg Sequist, Lecia V. Evans, Tracey L. Schneider, Bryan J. Keresztes, Roger Rogers, John S. de Mayolo, Jorge Antunez Feliciano, Josephine Yang, Yang Medeiros, Michelle Zaknoen, Sara L. TI Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of the Efficacy and Safety of Apricoxib in Combination With Either Docetaxel or Pemetrexed in Patients With Biomarker-Selected Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CYCLOOXYGENASE-2 EXPRESSION; BREAST-CANCER; CELECOXIB; ERLOTINIB; CHEMOTHERAPY; TRIAL AB Purpose Overexpression of COX-2 correlates with advanced stage and worse outcomes in non-small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2-dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of apricoxib to second-line docetaxel or pemetrexed. Patients and Methods Patients with NSCLC who had disease progression after one line of platinum-based therapy, performance status of 0 to 2, and normal organ function were potentially eligible. Only patients with a >= 50% decrease in urinary PGE-M after 5 days of treatment with apricoxib could enroll. Docetaxel 75 mg/m(2) or pemetrexed 500 mg/m(2) once every 21 days per the investigator was administered with apricoxib or placebo 400 mg once per day. The primary end point was progression-free survival (PFS). Exploratory analysis was performed regarding baseline urinary PGE-M and outcomes. Results In all, 101 patients completed screening, and 72 of the 80 who demonstrated >= 50% suppression were randomly assigned to apricoxib or placebo. Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib versus placebo. The median PFS for the control arm was 97 days (95% CI, 52 to 193 days) versus 85 days (95% CI, 67 to 142 days) for the experimental arm (P = .91). Conclusion Apricoxib did not improve PFS, despite biomarker-driven patient selection. (C) 2014 by American Society of Clinical Oncology C1 [Edelman, Martin J.; Feliciano, Josephine; Yang, Yang; Medeiros, Michelle] Univ Maryland Greenebaum Canc Ctr, Baltimore, MD 21136 USA. [Tan, Ming T.] Georgetown Univ, Washington, DC USA. [Fidler, Mary J.] Rush Univ Med Ctr, Chicago, IL USA. [Sanborn, Rachel E.] Providence Portland Med Ctr, Portland, OR USA. [Otterson, Greg] Ohio State Univ Comprehens Canc Ctr, Columbus, OH USA. [Sequist, Lecia V.] Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. [Evans, Tracey L.] Univ Penn, Philadelphia, PA 19104 USA. [Schneider, Bryan J.] Weill Cornell Med Coll, New York, NY USA. [Keresztes, Roger] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Rogers, John S.] West Virginia Univ Sch Med, Morgantown, WV USA. [de Mayolo, Jorge Antunez] Mercy Res Inst, Miami, FL USA. [Zaknoen, Sara L.] Tragara, San Diego, CA USA. RP Edelman, MJ (reprint author), Univ Maryland Greenebaum Canc Ctr, 22 South Greene St, Baltimore, MD 21136 USA. EM medelman@umm.edu FU Tragara Pharmaceuticals FX Although all authors completed the disclosure declaration, the following author(s) and/or an author's immediate family member(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: Jorge Antunez de Mayolo, Oncology and Radiation Associates (C), McKesson Health Solutions (C) Consultant or Advisory Role: Lecia V. Sequist, Clovis Oncology (U), Boehringer Ingelheim (U), AstraZeneca (U), Merrimack Pharmaceuticals (U), Novartis (U), Genentech (U), Taiho Pharmaceutical (U) Stock Ownership: Sara L. Zaknoen, Tragara Pharmaceuticals Honoraria: None Research Funding: Martin J. Edelman, Tragara Pharmaceuticals Expert Testimony: None Patents, Royalties, and Licenses: None Other Remuneration: None NR 13 TC 5 Z9 6 U1 2 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2015 VL 33 IS 2 BP 189 EP U96 DI 10.1200/JCO.2014.55.5789 PG 8 WC Oncology SC Oncology GA CF2ZX UT WOS:000352418100013 PM 25452446 ER PT J AU Frazier, AL Hale, JP Rodriguez-Galindo, C Dang, H Olson, T Murray, MJ Amatruda, JF Thornton, C Arul, GS Billmire, D Shaikh, F Pashankar, F Stoneham, S Krailo, M Nicholson, JC AF Frazier, A. Lindsay Hale, Juliet P. Rodriguez-Galindo, Carlos Dang, Ha Olson, Thomas Murray, Matthew J. Amatruda, James F. Thornton, Claire Arul, G. Suren Billmire, Deborah Shaikh, Furqan Pashankar, Farzana Stoneham, Sara Krailo, Mark Nicholson, James C. TI Revised Risk Classification for Pediatric Extracranial Germ Cell Tumors Based on 25 Years of Clinical Trial Data From the United Kingdom and United States SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHILDRENS ONCOLOGY GROUP; ALPHA-FETOPROTEIN; PROGNOSTIC-FACTORS; TESTICULAR-CANCER; STAGE-I; ETOPOSIDE; INTERGROUP; ADOLESCENT; BLEOMYCIN; CISPLATIN AB Purpose To risk stratify malignant extracranial pediatric germ cell tumors (GCTs). Patients and Methods Data from seven GCT trials conducted by the Children's Oncology Group (United States) or the Children's Cancer and Leukemia Group (United Kingdom) between 1985 and 2009 were merged to create a data set of patients with stage II to IV disease treated with platinum-based therapy. A parametric cure model was used to evaluate the prognostic importance of age, tumor site, stage, histology, tumor markers, and treatment regimen and estimate the percentage of patients who achieved long-term disease-free (LTDF) survival in each subgroup of the final model. Validation of the model was conducted using the bootstrap method. Results In multivariable analysis of 519 patients with GCTs, stage IV disease (P = .001), age >= 11 years (P = .001), and tumor site (P = .001) were significant predictors of worse LTDF survival. Elevated alpha-fetoprotein (AFP) >= 10,000 ng/mL was associated with worse outcome, whereas pure yolk sac tumor (YST) was associated with better outcome, although neither met criteria for statistical significance. The analysis identified a group of patients age > 11 years with either stage III to IV extragonadal tumors or stage IV ovarian tumors with predicted LTDF survival < 70%. A bootstrap procedure showed retention of age, tumor site, and stage in > 94%, AFP in 12%, and YST in 27% of the replications. Conclusion Clinical trial data from two large national pediatric clinical trial organizations have produced a new evidence-based risk stratification of malignant pediatric GCTs that identifies a poor-risk group warranting intensified therapy. (C) 2014 by American Society of Clinical Oncology C1 [Frazier, A. Lindsay; Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Boston, MA 02216 USA. [Frazier, A. Lindsay; Rodriguez-Galindo, Carlos] Boston Childrens Hosp, Boston, MA 02216 USA. [Hale, Juliet P.] Newcastle Upon Tyne Hosp Natl Hlth Serv NHS Fdn T, Newcastle Upon Tyne, Tyne & Wear, England. [Murray, Matthew J.; Amatruda, James F.] Cambridge Univ Hosp NHS Fdn Trust, Cambridge, England. [Murray, Matthew J.] Univ Cambridge, Cambridge, England. [Thornton, Claire] Royal Victoria Hosp, Belfast Hlth Trust, Belfast BT12 6BA, Antrim, North Ireland. [Arul, G. Suren] Birmingham Childrens Hosp NHS Fdn Trust, Birgmingham, W Midlands, England. [Stoneham, Sara] Univ Coll London Hosp Trusts, Childrens & Young Persons Canc Serv, London, England. [Dang, Ha] Childrens Oncol Grp, Philadelphia, PA USA. [Krailo, Mark] Univ So Calif, Los Angeles, CA USA. [Olson, Thomas] Emory Univ, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Amatruda, James F.] Childrens Med Ctr Dallas, Dallas, TX USA. [Billmire, Deborah] Riley Hosp Children, Indianapolis, IN USA. [Shaikh, Furqan] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Pashankar, Farzana] Yale Canc Ctr, New Haven, CT USA. RP Frazier, AL (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D-3127, Boston, MA 02216 USA. EM lindsay_frazier@dfci.harvard.edu FU Bridging the Gap Fund; Dana-Farber Cancer Institute; Katie Walker Cancer Trust; Teenage Cancer Trust; William Guy Forbeck Foundation FX Supported by the Bridging the Gap Fund, Dana-Farber Cancer Institute, Katie Walker Cancer Trust, Teenage Cancer Trust, and William Guy Forbeck Foundation. NR 26 TC 16 Z9 16 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2015 VL 33 IS 2 BP 195 EP U104 DI 10.1200/JCO.2014.58.3369 PG 8 WC Oncology SC Oncology GA CF2ZX UT WOS:000352418100014 PM 25452439 ER PT J AU Naghavi, M Wang, HD Lozano, R Davis, A Liang, XF Zhou, MG Vollset, SE Ozgoren, AA Abdalla, S Abd-Allah, F Aziz, MIA Abera, SF Aboyans, V Abraham, B Abraham, JP Abuabara, KE Abubakar, I Abu-Raddad, LJ Abu-Rmeileh, NME Achoki, T Adelekan, A Ademi, ZN Adofo, K Adou, AK Adsuar, JC Aernlov, J Agardh, EE Akena, D Al Khabouri, MJ Alasfoor, D Albittar, M Alegretti, MA Aleman, AV Alemu, ZA Alfonso-Cristancho, R Alhabib, S Ali, MK Ali, R Alla, F Al Lami, F Allebeck, P AlMazroa, MA Salman, RAS Alsharif, U Alvarez, E Alviz-Guzman, N Amankwaa, AA Amare, AT Ameli, O Amini, H Ammar, W Anderson, HR Anderson, BO Antonio, CAT Anwari, P Apfel, H Cunningham, SA Arsenijevic, VSA Al Artaman Asad, MM Asghar, RJ Assadi, R Atkins, LS Atkinson, C Badawi, A Bahit, MC Bakfalouni, T Balakrishnan, K Balalla, S Banerjee, A Barber, RM Barker-Collo, SL Barquera, S Barregard, L Barrero, LH Barrientos-Gutierrez, T Basu, A Basu, S Basulaiman, MO Beardsley, J Bedi, N Beghi, E Bekele, T Bell, ML Benjet, C Bennett, DA Bensenor, IM Benzian, H Bertozzi-Villa, A Beyene, TJ Bhala, N Bhalla, A Bhutta, ZA Bikbov, B Bin Abdulhak, A Biryukov, S Blore, JD Blyth, FM Bohensky, MA Borges, G Bose, D Boufous, S Bourne, RR Boyers, LN Brainin, M Brauer, M Brayne, CEG Brazinova, A Breitborde, N Brenner, H Briggs, ADM Brown, JC Brugha, TS Buckle, GC Bui, LN Bukhman, G Burch, M Nonato, IRC Carabin, H Cardenas, R Carapetis, J Carpenter, DO Caso, V Castaneda-Orjuela, CA Castro, RE Catala-Lopez, F Cavalleri, F Chang, JC Charlson, FC Che, X Chen, HL Chen, YY Chen, JS Chen, ZM Chiang, PPC Chimed-Ochir, O Chowdhury, R Christensen, H Christophi, CA Chuang, TW Chugh, SS Cirillo, M Coates, MM Coffeng, LE Coggeshall, MS Cohen, A Colistro, V Colquhoun, SM Colomar, M Cooper, LT Cooper, C Coppola, LM Cortinovis, M Courville, K Cowie, BC Criqui, MH Crump, JA Cuevas-Nasu, L Leite, IDC Dabhadkar, KC Dandona, L Dandona, R Dansereau, E Dargan, PI Dayama, A De la Cruz-Gongora, V de la Vega, SF De Leo, D Degenhardt, L del Pozo-Cruz, B Dellavalle, RP Deribe, K Jarlais, DCD Dessalegn, M deVeber, GA Dharmaratne, SD Dherani, M Diaz-Ortega, JL Diaz-Torne, C Dicker, D Ding, EL Dokova, K Dorsey, ER Driscoll, TR Duan, LL Duber, HC Durrani, AM Ebel, BE Edmond, KM Ellenbogen, RG Elshrek, Y Ermakov, SP Erskine, HE Eshrati, B Esteghamati, A Estep, K Furst, T Fahimi, S Fahrion, AS Faraon, EJA Farzadfar, F Fay, DFJ Feigl, AB Feigin, VL Felicio, MM Fereshtehnejad, SM Fernandes, JG Ferrari, AJ Fleming, TD Foigt, N Foreman, K Forouzanfar, MH Fowkes, FGR Paleo, UF Franklin, RC Futran, ND Gaffikin, L Gambashidze, K Gankpe, FG Garcia-Guerra, FA Garcia, AC Geleijnse, JM Gessner, BD Gibney, KB Gillum, RF Gilmour, S Abdelmageem, I Ginawi, M Giroud, M Glaser, EL Goenka, S Dantes, HG Gona, P Gonzalez-Medina, D Guinovart, C Gupta, R Gupta, R Gosselin, RA Gotay, CC Goto, A Gowda, HN Graetz, N Greenwell, KF Gugnani, HC Gunnell, D Gutierrez, RA Haagsma, J Hafezi-Nejad, N Hagan, H Hagstromer, M Halasa, YA Hamadeh, RR Hamavid, H Hammami, M Hancock, J Hankey, GJ Hansen, GM Harb, HL Harewood, H Haro, JM Havmoeller, R Hay, RJ Hay, SI Hedayati, MT Pi, IBH Heuton, KR Heydarpour, P Higashi, H Hijar, M Hoek, HW Hoffman, HJ Hornberger, JC Hosgood, HD Hossain, M Hotez, PJ Hoy, DG Hsairi, M Hu, GQ Huang, JJ Huffman, MD Hughes, AJ Husseini, A Huynh, C Iannarone, M Iburg, KM Idrisov, BT Ikeda, N Innos, K Inoue, M Islami, F Ismayilova, S Jacobsen, KH Jassal, S Jayaraman, SP Jensen, PN Jha, V Jiang, GH Jiang, Y Jonas, JB Joseph, J Juel, K Kabagambe, EK Kan, HD Karch, A Karimkhani, C Karthikeyan, G Kassebaum, N Kaul, A Kawakami, N Kazanjan, K Kazi, DS Kemp, AH Kengne, AP Keren, A Kereselidze, M Khader, YS Khalifa, SEAH Khan, EA Khan, G Khang, YH Kieling, C Kinfu, Y Kinge, JM Kim, D Kim, S Kivipelto, M Knibbs, L Knudsen, AK Kokubo, Y Kosen, S Kotagal, M Kravchenko, MA Krishnaswami, S Krueger, H Defo, BK Kuipers, EJ Bicer, BK Kulkarni, C Kulkarni, VS Kumar, K Kumar, RB Kwan, GF Kyu, H Lai, T Balaji, AL Lalloo, R Lallukka, T Lam, H Lan, Q Lansingh, VC Larson, HJ Larsson, A Lavados, PM Lawrynowicz, AEB Leasher, JL Lee, JT Leigh, J Leinsalu, M Leung, R Levitz, C Li, B Li, YC Li, YM Liddell, C Lim, SS de Lima, GMF Lind, ML Lipshultz, SE Liu, SW Liu, Y Lloyd, BK Lofgren, KT Logroscino, G London, SJ Lortet-Tieulent, J Lotufo, PA Lucas, RM Lunevicius, R Lyons, RA Ma, S Machado, VMP MacIntyre, MF Mackay, MT MacLachlan, JH Magis-Rodriguez, C Mahdi, AA Majdan, M Malekzadeh, R Mangalam, S Mapoma, CC Marape, M Marcenes, W Margono, C Marks, GB Marzan, MB Masci, JR Mashal, MTQ Masiye, F Mason-Jones, AJ Matzopolous, R Mayosi, BM Mazorodze, TT McGrath, JJ Mckay, AC Mckee, M McLain, A Meaney, PA Mehndiratta, MM Mejia-Rodriguez, F Melaku, YA Meltzer, M Memish, ZA Mendoza, W Mensah, GA Meretoja, A Mhimbira, FA Miller, TR Mills, EJ Misganaw, A Mishra, SK Mock, CN Moffitt, TE Ibrahim, NM Mohammad, KA Mokdad, AH Mola, GL Monasta, L Monis, JD Hernandez, JCM Montico, M Montine, TJ Mooney, MD Moore, AR Moradi-Lakeh, M Moran, AE Mori, R Moschandreas, J Moturi, WN Moyer, ML Mozaffarian, D Mueller, UO Mukaigawara, M Mullany, EC Murray, J Mustapha, A Naghavi, P Naheed, A Naidoo, KS Naldi, L Nand, D Nangia, V Narayan, KMV Nash, D Nasher, J Nejjari, C Nelson, RG Neuhouser, M Neupane, SP Newcomb, PA Newman, L Newton, CR Ng, M Ngalesoni, FN Nguyen, G Nguyen, NTT Nisar, MI Nolte, S Norheim, OF Norman, RE Norrving, B Nyakarahuka, L Odell, S O'Donnell, M Ohkubo, T Ohno, SL Olusanya, BO Omer, SB Opio, JN Orisakwe, OE Ortblad, KF Ortiz, A Otayza, MLK Pain, AW Pandian, JD Panelo, CI Panniyammakal, J Papachristou, C Caicedo, AJP Patten, SB Patton, GC Paul, VK Pavlin, B Pearce, N Pellegrini, CA Pereira, DM Peresson, SC Perez-Padilla, R Perez-Ruiz, FP Perico, N Pervaiz, A Pesudovs, K Peterson, CB Petzold, M Phillips, BK Phillips, DE Phillips, MR Plass, D Piel, FB Poenaru, D Polinder, S Popova, S Poulton, RG Pourmalek, F Prabhakaran, D Qato, D Quezada, AD Quistberg, DA Rabito, F Rafay, A Rahimi, K Rahimi-Movaghar, V Rahman, SUR Raju, M Rakovac, I Rana, SM Refaat, A Remuzzi, G Ribeiro, AL Ricci, S Riccio, PM Richardson, L Richardus, JH Roberts, B Roberts, DA Robinson, M Roca, A Rodriguez, A Rojas-Rueda, D Ronfani, L Room, R Roth, GA Rothenbacher, D Rothstein, DH Rowley, JT Roy, N Ruhago, GM Rushton, L Sambandam, S Soreide, K Saeedi, MY Saha, S Sahathevan, R Sahraian, MA Sahle, BW Salomon, JA Salvo, D Samonte, GMJ Sampson, U Sanabria, JR Sandar, L Santos, IS Satpathy, M Sawhney, M Saylan, M Scarborough, P Schottker, B Schmidt, JC Schneider, IJC Schumacher, AE Schwebel, DC Scott, JG Sepanlou, SG Servan-Mori, EE Shackelford, K Shaheen, A Shahraz, S Shakh-Nazarova, M Shangguan, S She, J Sheikhbahaei, S Shepard, DS Shibuya, K Shinohara, Y Shishani, K Shiue, I Shivakoti, R Shrime, MG Sigfusdottir, ID Silberberg, DH Silva, AP Simard, EP Sindi, S Singh, JA Singh, L Sioson, E Skirbekk, V Sliwa, K So, S Soljak, M Soneji, S Soshnikov, SS Sposato, LA Sreeramareddy, CT Stanaway, JRD Stathopoulou, VK Steenland, K Stein, C Steiner, C Stevens, A Stoeckl, H Straif, K Stroumpoulis, K Sturua, L Sunguya, BF Swaminathan, S Swaroop, M Sykes, BL Tabb, KM Takahashi, K Talongwa, RT Tan, F Tanne, D Tanner, M Tavakkoli, M Ao, BT Teixeira, CM Templin, T Tenkorang, EY Terkawi, AS Thomas, BA Thorne-Lyman, AL Thrift, AG Thurston, GD Tillmann, T Tirschwell, DL Tleyjeh, IM Tonelli, M Topouzis, F Towbin, JA Toyoshima, H Traebert, J Tran, BX Truelsen, T Trujillo, U Trillini, M Dimbuene, ZT Tsilimbaris, M Tuzcu, EM Ubeda, C Uchendu, US Ukwaja, KN Undurraga, EA Vallely, AJ van de Vijver, S van Gool, CH Varakin, YY Vasankari, TJ Vasconcelos, AMN Vavilala, MS Venketasubramanian, N Vijayakumar, L Villalpando, S Violante, FS Vlassov, VV Wagner, GR Waller, SG Wang, JL Wang, L Wang, XR Wang, YP Warouw, TS Weichenthal, S Weiderpass, E Weintraub, RG Wenzhi, W Werdecker, A Wessells, KRR Westerman, R Whiteford, HA Wilkinson, JD Williams, TN Woldeyohannes, SM Wolfe, CDA Wolock, TM Woolf, AD Wong, JQ Wright, JL Wulf, S Wurtz, B Xu, GL Yang, YC Yano, Y Yatsuya, H Yip, P Yonemoto, N Yoon, SJ Younis, M Yu, CH Jin, KY Zaki, MES Zamakhshary, MF Zeeb, H Zhang, Y Zhao, Y Zheng, YF Zhu, J Zhu, S Zonies, D Zou, XN Zunt, JR Vos, T Lopez, AD Murray, CJL AF Naghavi, Mohsen Wang, Haidong Lozano, Rafael Davis, Adrian Liang, Xiaofeng Zhou, Maigeng Vollset, Stein Emil Ozgoren, Ayse Abbasoglu Abdalla, Safa Abd-Allah, Foad Aziz, Muna I. 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Truelsen, Thomas Trujillo, Ulises Trillini, Matias Dimbuene, Zacharie Tsala Tsilimbaris, Miltiadis Tuzcu, E. Murat Ubeda, Clotilde Uchendu, Uche S. Ukwaja, Kingsley N. Undurraga, Eduardo A. Vallely, Andrew J. van de Vijver, Steven van Gool, Coen H. Varakin, Yuri Y. Vasankari, Tommi J. Vasconcelos, Ana Maria Nogales Vavilala, Monica S. Venketasubramanian, N. Vijayakumar, Lakshmi Villalpando, Salvador Violante, Francesco S. Vlassov, Vasiliy Victorovich Wagner, Gregory R. Waller, Stephen G. Wang, JianLi Wang, Linhong Wang, XiaoRong Wang, Yanping Warouw, Tati Suryati Weichenthal, Scott Weiderpass, Elisabete Weintraub, Robert G. Wenzhi, Wang Werdecker, Andrea Wessells, K. Ryan R. Westerman, Ronny Whiteford, Harvey A. Wilkinson, James D. Williams, Thomas Neil Woldeyohannes, Solomon Meseret Wolfe, Charles D. A. Wolock, Timothy M. Woolf, Anthony D. Wong, John Q. Wright, Jonathan L. Wulf, Sarah Wurtz, Brittany Xu, Gelin Yang, Yang C. Yano, Yuichiro Yatsuya, Hiroshi Yip, Paul Yonemoto, Naohiro Yoon, Seok-Jun Younis, Mustafa Yu, Chuanhua Jin, Kim Yun Zaki, Maysaa El Sayed Zamakhshary, Mohammed Fouad Zeeb, Hajo Zhang, Yong Zhao, Yong Zheng, Yingfeng Zhu, Jun Zhu, Shankuan Zonies, David Zou, Xiao Nong Zunt, Joseph R. Vos, Theo Lopez, Alan D. Murray, Christopher J. L. CA GBD Mortal 2013 Causes Death Colla TI Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 SO LANCET LA English DT Article ID INFLUENZAE TYPE-B; PNEUMOCOCCAL CONJUGATE VACCINE; PLACEBO-CONTROLLED-TRIAL; 187 COUNTRIES; RISK-FACTORS; ENTERIC MULTICENTER; CHILDREN YOUNGER; CHILDHOOD PNEUMONIA; INTEGRATED APPROACH; POPULATION HEALTH AB Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade. C1 [Naghavi, Mohsen; Wang, Haidong; Lozano, Rafael; Vollset, Stein Emil; Achoki, Tom; Apfel, Henry; Atkinson, Charles; Barber, Ryan M.; Bertozzi-Villa, Amelia; Biryukov, Stan; Brown, Jonathan C.; Catala-Lopez, Ferrn; Coates, Matthew M.; Coffeng, Luc Edgar; Coggeshall, Megan S.; Dandona, Lalit; Dansereau, Emily; Dicker, Daniel; Duber, Herbert C.; Estep, Kara; Fleming, Thomas D.; Forouzanfar, Mohammad H.; Gonzalez-Medina, Diego; Graetz, Nicholas; Haagsma, Juanita; Hamavid, Hannah; Hancock, Jamie; Hansen, Gillian M.; Heuton, Kyle R.; Higashi, Hideki; Huynh, Chantal; Iannarone, Marissa; Joseph, Jonathan; Kassebaum, Nicholas; Kyu, Hmwe; Levitz, Carly; Liddell, Chelsea; Lind, Maggie L.; Lofgren, Katherine T.; MacIntyre, Michael F.; Margono, Christopher; McLain, Abigail; Mokdad, Ali H.; Mooney, Meghan D.; Moradi-Lakeh, Maziar; Moyer, Madeline L.; Mullany, Erin C.; Naghavi, Paria; Ng, Marie; Nguyen, Grant; Odell, Shaun; Ohno, Summer Lockett; Ortblad, Katrina F.; Pain, Amanda W.; Phillips, Bryan K.; Phillips, David E.; Richardson, Lee; Roberts, D. Allen; Robinson, Margaret; Roth, Gregory A.; Sandar, Logan; Schumacher, Austin E.; Shackelford, Katya; Singh, Lavanya; Sioson, Edgar; Stanaway, Jeff Rey D.; Steiner, Caitlyn; Stevens, Antony; Templin, Tara; Thomas, Bernadette A.; Wolock, Timothy M.; Wulf, Sarah; Wurtz, Brittany; Vos, Theo; Murray, Christopher J. L.] Inst Hlth Metr & Evaluat, Seattle, WA USA. [Ellenbogen, Richard G.; Wright, Jonathan L.] Univ Washington, Sch Med, Seattle, WA USA. [Kassebaum, Nicholas] Childrens Hosp, Seattle, WA USA. [Tirschwell, David L.] Dept Neurol, Seattle, WA USA. [Ebel, Beth E.] Univ Washington, Harborview Med Ctr, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA. [Alfonso-Cristancho, Rafael; Anderson, Benjamin O.; Futran, Neal D.; Jensen, Paul N.; Kotagal, Meera; Mock, Charles N.; Montine, Thomas J.; Pellegrini, Carlos A.; Quistberg, D. Alex; Vavilala, Monica S.; Zunt, Joseph R.] Univ Washington, Seattle, WA 98195 USA. 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[Vollset, Stein Emil; Norheim, Ole F.] Univ Bergen, Bergen, Norway. [Ozgoren, Ayse Abbasoglu; Bicer, Burcu Kucuk] Hacettepe Univ, Inst Populat Studies, Ankara, Turkey. [Abdalla, Safa] Sudanese Publ Hlth Consultancy Grp, Solihull, W Midlands, England. [Abd-Allah, Foad] Cairo Univ, Fac Med, Cairo, Egypt. [Aziz, Muna I. Abdel] Inst Publ Hlth, Khartoum, Sudan. [Abera, Semaw Ferede] Coll Hlth Sci, Sch Publ Hlth, Mekelle, Tigray, Ethiopia. [Melaku, Yohannes Adama; Sahle, Berhe Weldearegawi] Mekelle Univ, Mekelle, Tigray, Ethiopia. [Aboyans, Victor] Dupuytren Univ Hosp, Limoges, France. [Abraham, Biju] Oslo & Akershus Univ, Coll Appl Sci HiOA, Oslo, Norway. [Abraham, Jerry P.] Univ Texas San Antonio, Sch Med, San Antonio, TX USA. [Abuabara, Katrina E.; Silberberg, Donald H.] Univ Penn, Philadelphia, PA 19104 USA. [Benzian, Habib] Dept Epidemiol & Publ Hlth, London, England. [Benzian, Habib] UCL, London, England. [Abu-Raddad, Laith J.] Weill Cornell Med Coll Qatar, Doha, Qatar. 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[Al Khabouri, Mazin J.; Alasfoor, Deena] Minist Hlth, Muscat, Oman. [Al Lami, Faris] Baghdad Coll Med, Baghdad, Iraq. [Albittar, Mohammed] Independent, Damascus, Syria. Grp Invest Ciencias Salud & Neurociencias CISNEUR, Cartagena De Indias, Bolivar, Colombia. [Alegretti, Miguel Angel; Aleman, Alicia V.; Cavalleri, Fiorella; Colistro, Valentina] Univ Republica, Fac Med, Dept Prevent & Social Med, Montevideo, Uruguay. [Alemu, Zewdie Aderaw] Debre Markos Univ, Debre Markos, Amhara, Ethiopia. [Alhabib, Samia] Natl Guard Hlth Affairs, Riyadh, Saudi Arabia. [Simard, Edgar P.; Steenland, Kyle] Rollins Sch Publ Hlth, Atlanta, GA USA. [Ali, Mohammed K.; Cunningham, Solveig Argeseanu; Dabhadkar, Kaustubh C.; Liu, Yang; Narayan, K. M. Venkat; Omer, Saad B.; Phillips, Michael R.] Emory Univ, Atlanta, GA 30322 USA. [Ali, Raghib; Bennett, Derrick A.; Briggs, Adam D. M.; Chen, Zhengming; Hay, Simon I.; Piel, Frederic Bernard; Rahimi, Kazem; Scarborough, Peter] Univ Oxford, Oxford, England. [Alla, Francois] Univ Lorraine, Sch Publ Hlth, Nancy, France. [Allebeck, Peter] Dept Publ Hlth Sci, Stockholm, Sweden. [Fereshtehnejad, Seyed-Mohammad] Dept Neurobiol Care Sci & Soc NVS, Stockholm, Sweden. [Kivipelto, Miia] Aging Res Ctr, Stockholm, Sweden. [Weiderpass, Elisabete] Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Hagstromer, Maria; Havmoeller, Rasmus; Sindi, Shireen] Karolinska Inst, Stockholm, Sweden. [AlMazroa, Mohammad A.; Basulaiman, Mohammed Omar; Memish, Ziad A.; Saeedi, Mohammad Yahya] Saudi Minist Hlth, Riyadh, Saudi Arabia. [Salman, Rustam Al-Shahi; Fowkes, F. Gerry R.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Alsharif, Ubai; Nolte, Sandra; Papachristou, Christina] Charite, D-13353 Berlin, Germany. [Alvarez, Elena] Government, Madrid, Spain. [Alviz-Guzman, Nelson; Paternina Caicedo, Angel J.] Univ Cartagena, Cartagena De Indias, Colombia. [Amankwaa, Adansi A.] Albany State Univ, Albany, GA 31705 USA. [Amare, Azmeraw T.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Amare, Azmeraw T.] Bahir Dar Univ, Coll Med & Hlth Sci, Bahir Dar, Ethiopia. [Ameli, Omid] Boston Univ, Boston, MA 02215 USA. [Amini, Hassan] Kurdistan Univ Med Sci, Kurdistan Environm Hlth Res Ctr, Sanandaj, Kurdistan, Iran. [Amini, Hassan] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland. [Tanner, Marcel] Univ Basel, Basel, Switzerland. [Ammar, Walid] Minist Publ Hlth, Beirut, Lebanon. [Anderson, H. Ross] St Georges Univ London, London, England. [Antonio, Carl Abelardo T.; Faraon, Emerito Jose A.; Panelo, Carlo Irwin] Univ Philippines Manila, Coll Publ Hlth, Manila, Philippines. [Anwari, Palwasha] UNFPA, Kabul, Afghanistan. [Arsenijevic, Valentina S. Arsic] Univ Belgrade, Sch Med, Inst Microbiol & Immunol, Belgrade, Serbia. [Al Artaman] Evidera Inc, Lexington, MA USA. [Asad, Majed Masoud] Minist Hlth, Amman, Jordan. [Asghar, Rana J.] South Asian Publ Hlth Forum, Islamabad, Pakistan. [Assadi, Reza] Mashhad Univ Med Sci, Mashhad, Khorasan Razavi, Iran. [Atkins, Lydia S.] Minist Hlth Wellness Human Serv & Gender Relat, Castries, St Lucia. [Badawi, Alaa] Publ Hlth Agcy Canada, Toronto, ON, Canada. [Bahit, Maria C.] INECO Neurociencias, Santa Fe, NM USA. [Bakfalouni, Talal] Minist Hlth, Damascus, Syria. [Balakrishnan, Kalpana] Sri Ramachandra Univ, Madras, Tamil Nadu, India. [Balalla, Shivanthi; Feigin, Valery L.] Natl Inst Stroke & Appl Neurosciences, Auckland, New Zealand. [Barker-Collo, Suzanne L.] Sch Psychol, Auckland, New Zealand. [del Pozo-Cruz, Borja] Univ Auckland, Auckland 1, New Zealand. [Banerjee, Amitava] Univ Birmingham, Birmingham, W Midlands, England. [Barregard, Lars] Univ Gothenburg, Dept Environm & Occupat Hlth, Gothenburg, Sweden. [Barrero, Lope H.] Pontificia Univ Javeriana, Dept Ind Engn, Bogota, Colombia. [Basu, Arindam] Univ Canterbury, Sch Hlth Sci, Canterbury, New Zealand. 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[Bhalla, Ashish] Postgrad Inst Med Educ & Res, Chandigarh 160012, UT, India. [Bhutta, Zulfiqar A.] Med Ctr, Karachi, Pakistan. [Nisar, Muhammad Imran] Aga Khan Univ, Karachi, Pakistan. [Bikbov, Boris] I Evdokimov Moscow State Univ Med & Dent, Moscow, Russia. [Bin Abdulhak, Aref] Univ Missouri, Kansas City, MO 64110 USA. [Marks, Guy B.] Woolcock Inst Med Res, Sydney, NSW, Australia. [Driscoll, Tim R.] Sydney Sch Publ Hlth, Sydney, NSW, Australia. [Blyth, Fiona M.; Leigh, James] Univ Sydney, Sydney, NSW 2006, Australia. [Borges, Guilherme] Inst Nacl Psiquiatria, Mexico City, DF, Mexico. [Bose, Dipan] World Bank, Washington, DC 20433 USA. [Boufous, Soufiane] Transport & Rd Safety TARS Res, Sydney, NSW, Australia. [Vallely, Andrew J.] Kirby Inst, Sydney, NSW, Australia. [Degenhardt, Louisa; Satpathy, Maheswar] Univ New S Wales, Sydney, NSW, Australia. [Bourne, Rupert R.] Anglia Ruskin Univ, Vis & Eye Res Unit, Cambridge, England. [Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA. [Brainin, Michael] Danube Univ Krems, Krems, Austria. [Krueger, Hans] Sch Populat & Publ Hlth, Vancouver, BC, Canada. [Brauer, Michael; Gotay, Carolyn C.; Pourmalek, Farshad] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Brayne, Carol E. G.] Cambridge Inst Publ Hlth, Cambridge, England. [Brazinova, Alexandra; Majdan, Marek] Trnava Univ, Fac Hlth Sci & Social Work, Trnava, Slovakia. [Breitborde, Nicholas] Univ Arizona, Tucson, AZ USA. [Brenner, Hermann] German Canc Res Ctr, Heidelberg, Germany. [Brugha, Traolach S.] Univ Leicester, Leicester, Leics, England. [Buckle, Geoffrey C.; Gona, Philimon] Univ Massachusetts, Sch Med, Worcester, MA USA. [Bui, Linh Ngoc; Nhung Thi Trang Nguyen] Hanoi Sch Publ Hlth, Hanoi, Vietnam. [Bukhman, Gene] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ding, Eric L.; Fahimi, Saman; Shangguan, Siyi] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Feigl, Andrea B.; Salomon, Joshua A.; Shrime, Mark G.] Harvard Univ, Cambridge, MA 02138 USA. [Burch, Michael] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Cardenas, Rosario] Univ Autonoma Metropolitana, Mexico City, DF, Mexico. [Carabin, Helesne] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK USA. [Carapetis, Jonathan] Telethon Inst Child Hlth Res, Subiaco, WA, Australia. [Carpenter, David O.] Univ Albany, Rensselaer, NY USA. [Caso, Valeria] Univ Perugia, Stroke Unit, I-06100 Perugia, Italy. [Castaneda-Orjuela, Carlos A.] Colombian Natl Hlth Observ, Inst Nacl Salud, Bogota, Colombia. [Castro, Ruben Estanislao] Univ Diego Portales, Santiago, Chile. [Catala-Lopez, Ferrn] Minist Hlth, Spanish Med & Healthcare Prod Agcy AEMPS, Div Pharmacoepidemiol & Pharmacovigilance, Madrid, Spain. [Chang, Jung-Chen] Natl Taiwan Univ, Taipei 10764, Taiwan. [Hoy, Damian G.] Univ Queensland, Sch Populat Hlth, Herston, Qld, Australia. [Scott, James G.] Univ Queensland, Clin Res Ctr, Herston, Qld, Australia. [Charlson, Fiona C.; Erskine, Holly E.; Ferrari, Alize J.; Knibbs, Luke; McGrath, John J.; Norman, Rosana E.; Whiteford, Harvey A.] Univ Queensland, Brisbane, Qld, Australia. [Che, Xuan] NIH, Bethesda, MD 20892 USA. [She, Jun] Zhongshan Hosp, Shanghai, Peoples R China. [Chen, Yingyao; Kan, Haidong] Fudan Univ, Shanghai 200433, Peoples R China. [Chen, Zhengming] CTSU, Nuffield Dept Populat Hlth, Oxford, England. [Chen, Honglei; London, Stephanie J.] NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv,RTP,NC USA, Res Triangle Pk, NC 27709 USA. [Chen, Jian Sheng] Inst Bone & Joint Res, St Laonards, NSW, Australia. [Chimed-Ochir, Odgerel] Univ Occupat & Environm Hlth, Dept Environm Epidemiol, Kitakyushu, Fukuoka 807, Japan. [Chowdhury, Rajiv; Murray, Christopher J. L.] Univ Cambridge, Cambridge, England. [Christensen, Hanne] Bispebjerg Hosp, Copenhagen, Denmark. [Christophi, Costas A.] Cyprus Univ Technol, Limassol, Cyprus. [Chang, Jung-Chen] Taipei Med Univ, Sch Med, Dept Mol Parasitol & Trop Dis, Taipei, Taiwan. [Chuang, Ting-Wu] Taipei Med Univ, Ctr Int Trop Med, Coll Med, Taipei, Taiwan. [Chugh, Sumeet S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Cirillo, Massimo] Univ Salerno, I-84081 Baronissi, SA, Italy. [Cohen, Aaron] Hlth Effects Inst, Boston, MA USA. [Colomar, Mercedes] UNICEM, Montevideo, Uruguay. [Cooper, Cyrus] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Cooper, Cyrus; Tleyjeh, Imad M.] Mayo Clin, Rochester, MN USA. [Coppola, Luis M.] Hosp Municipal Ramon Santamarina, Buenos Aires, DF, Argentina. [Cowie, Benjamin C.; MacLachlan, Jennifer H.] Victorian Infect Dis Reference Lab, North Melbourne, Vic, Australia. [Criqui, Michael H.; Jassal, Simerjot] Univ Calif San Diego, La Jolla, CA 92093 USA. [Crump, John A.] Dunedin Sch Med, Ctr Int Hlth, Dunedin, Otago, New Zealand. [Poulton, Richie G.] Univ Otago, Dunedin, Otago, New Zealand. [Leite, Iuri da Costa] Natl Sch Publ Hlth ENSP Fiocruz, Rio De Janeiro, Brazil. [Dandona, Lalit; Dandona, Rakhi; Goenka, Shifalika] Publ Hlth Fdn India, New Delhi, India. [Dandona, Rakhi; Goenka, Shifalika] Indian Inst Publ Hlth, New Delhi, India. [Dargan, Paul I.] Guys & St Thomas NHS Fdn Trust, London, England. [Dayama, Anand] Jacobi Med Ctr, Dept Surg, Atlanta, GA USA. [de la Vega, Shelley F.] Univ Philippines, Inst Aging, Manila, Philippines. [Lam, Hilton] Univ Philippines, Natl Inst Hlth, Inst Hlth Policy & Dev Studies, Manila, Philippines. [De Leo, Diego] Griffith Univ, Brisbane, Qld 4111, Australia. [Uchendu, Uche S.] US Dept Vet Affairs, Washington, DC USA. [Dellavalle, Robert P.] Eastern Colorado Healthcare Syst, Denver, CO USA. [Jarlais, Don C. Des] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Dessalegn, Muluken] Africa Med & Res Fdn Ethiopia, Addis Ababa, Ethiopia. [deVeber, Gabrielle A.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Dharmaratne, Samath D.] Univ Peradeniya, Peradeniya, Sri Lanka. [Dherani, Mukesh] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Diaz-Torne, Cesar] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Dokova, Klara] Med Univ Varna, Fac Publ Hlth, Dept Social Med, Varna, Bulgaria. [Dorsey, E. Ray] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Durrani, Adnan M.] NIH, Montgomery, MD USA. [Hankey, Graeme J.] Sch Med & Pharmacol, Perth, WA, Australia. [Kabagambe, Edmond Kato] Univ Western Australia, Perth, WA 6009, Australia. [Elshrek, Yousef] Univ Tripoli, Fac Agr, Dept Food Sci, Tripoli, Libya. [Ermakov, Sergey Petrovich] Russian Acad Sci, Inst Social & Econ Studies Populat, Moscow, Russia. [Eshrati, Babak] Arak Univ Med Sci & Hlth Affairs, Arak, Markazi, Iran. [Esteghamati, Alireza; Hafezi-Nejad, Nima; Sheikhbahaei, Sara] Endocrinol & Metab Res Ctr, Tehran, Iran. [Farzadfar, Farshad] Noncommunicable Dis Reesearch Ctr, Tehran, Iran. [Malekzadeh, Reza; Sepanlou, Sadaf G.] Digest Dis Res Ctr, Tehran, Iran. [Rahimi-Movaghar, Vafa] Sina Trauma & Surg Res Ctr, Tehran, Iran. [Sahraian, Mohammad Ali] Res Ctr, Tehran, Iran. [Moradi-Lakeh, Maziar] Dept Community Med, Tehran, Iran. [Heydarpour, Pouria] Univ Tehran Med Sci, Tehran, Iran. [Fuerst, Thomas] Ctr Hlth Policy, London, England. [Fuerst, Thomas] Dept Infect Dis Epidemiol, London, England. [Mustapha, Adetoun] MRC PHE Ctr Hlth & Environm, London, England. [Foreman, Kyle; Rodriguez, Alina; Rushton, Lesley; Soljak, Michael; Williams, Thomas Neil] Univ London Imperial Coll Sci Technol & Med, London, England. [Vollset, Stein Emil] Div Informat Evidence Res & Innovat, Copenhagen, Denmark. [Fahrion, Anna S.; Rakovac, Ivo] WHO, Reg Off Europe, DK-2100 Copenhagen, Denmark. [Newman, Lori] WHO, CH-1211 Geneva, Switzerland. [Teixeira, Carolina Maria] ARS Norte, Oporto, Portugal. [Felicio, Manuela Mendonca; de Lima, Graca Maria Ferreira; Machado, Vasco Manuel Pedro] IP Dept Saude Publ, Oporto, Portugal. [Fernandes, Jefferson G.] German Hosp Oswaldo Cruz, Inst Educ & Sci, Sao Paulo, Brazil. [Foigt, Nataliya] Ukraine Acad Med Sci, Inst Gerontol, UA-252655 Kiev, Ukraine. [Franklin, Richard C.] James Cook Univ, Townsville, Qld 4811, Australia. [Gambashidze, Ketevan; Kazanjan, Konstantin; Kereselidze, Maia; Shakh-Nazarova, Marina; Sturua, Lela] Natl Ctr Dis Control & Publ Hlth, Tbilisi, Rep of Georgia. [Gankpe, Fortune Gbetoho] Clin Cooperat Parakou, Parakou, Borgou, Benin. [Garcia, Ana Cristina] Publ Hlth Unit Primary Hlth Care Grp Almada Seixa, Almada, Setubal, Portugal. [Geleijnse, Johanna M.] Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands. [Gessner, Bradford D.] Agence Med Prevent, Paris, France. [Lloyd, Belinda K.] Eastern Hlth Clin Sch, Melbourne, Vic, Australia. [Gibney, Katherine B.; Thrift, Amanda G.] Monash Univ, Melbourne, Vic 3004, Australia. [Gillum, Richard F.] Howard Univ, Washington, DC 20059 USA. [Inoue, Manami] Grad Sch Med, Tokyo, Japan. [Kawakami, Norito] Sch Publ Hlth, Tokyo, Japan. [Gilmour, Stuart; Shibuya, Kenji] Univ Tokyo, Tokyo, Japan. [Ginawi, Mohamed] Univ Hail, Coll Med, Hail, Saudi Arabia. [Giroud, Maurice] Univ Hosp Dijon, Dijon France, Region Of Burgo, France. [Glaser, Elizabeth L.; Halasa, Yara A.; Idrisov, Bulat T.; Shahraz, Saeid; Shepard, Donald S.; Undurraga, Eduardo A.] Brandeis Univ, Waltham, MA USA. [Gosselin, Richard A.; Kazi, Dhruv S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goto, Atsushi] Natl Ctr Global Hlth & Med, Dept Diabet Res, Tokyo, Japan. [Gugnani, Harish Chander] St James Sch Med, Kralendijk, Bonaire, Netherlands. [Guinovart, Caterina] PATH, Seattle, WA USA. [Gunnell, David] Univ Bristol, Bristol, Avon, England. [Gupta, Rahul] Fortis Escorts Hosp, Jaipur, Rajasthan, India. [Gupta, Rajeev] Kanawha Charleston Hlth Dept, Charleston, WV USA. [Thurston, George D.] NYU, Nelson Inst Environm Med, Tuxedo Pk, NY USA. [Hagan, Holly] NYU, New York, NY USA. [Hamadeh, Randah Ribhi] Arabian Gulf Univ, Manama, Bahrain. [Hammami, Mouhanad] Wayne Cty Dept Hlth & Human Serv, Detroit, MI USA. [Harewood, Heather] Eunice Gibson Polyclin, Bridgetown, St Michael, Barbados. [Haro, Josep Maria] Univ Barcelona, CIBERSAM, Barcelona, Spain. [Hay, Roderick J.] Int Fdn Dermatol, London, England. [Hedayati, Mohammad T.] Mazandaran Univ Med Sci, Sari, Mazandaran, Iran. [Hijar, Martha] Fdn Entornos AC, Cuernavaca, Morelos, Mexico. [Hoek, Hans W.] Parnassia Psychiat Inst, The Hague, Netherlands. [Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. [Hornberger, John C.] Cedar Associates, Menlo Pk, CA USA. [Hosgood, H. Dean] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Hossain, Mazeda; Larson, Heidi J.; Mckee, Martin; Pearce, Neil; Roberts, Bayard; Stoeckl, Heidi; Tillmann, Taavi] London Sch Hyg & Trop Med, London WC1, England. [Hotez, Peter J.] Baylor Coll Med, Houston, TX 77030 USA. [Hoy, Damian G.] Secretariat Pacific Commun, Publ Hlth Div, Herston, Qld, Australia. [Hsairi, Mohamed] Natl Inst Publ Hlth MOH, Tunis, Tunisia. [Hu, Guoqing] Univ Toronto, Toronto, ON, Canada. [Hu, Guoqing] Cent S Univ, Changsha, Hunan, Peoples R China. [Huffman, Mark D.] Feinberg Sch Med, Chicago, IL USA. [Swaroop, Mamta] Northwestern Univ, Chicago, IL 60611 USA. [Husseini, Abdullatif] Qatar Univ, Publ Hlth Program, Birzeit, Ramallah, Israel. [Iburg, Kim M.] Aarhus Univ, Aarhus, Denmark. [Ikeda, Nayu] Natl Inst Hlth & Nutr, Bunkyo Ku, Tokyo 162, Japan. [Innos, Kaire; Leinsalu, Mall] Natl Inst Hlth Dev, Tallinn, Estonia. [Islami, Farhad] Amer Canc Soc, New York, NY USA. [Ismayilova, Samaya] Self Employed, Baku, Azerbaijan. [Jacobsen, Kathryn H.] George Mason Univ, Fairfax, VA 22030 USA. [Jassal, Simerjot] VA San Diego, San Diego, CA USA. [Jayaraman, Sudha P.] Virginia Commonwealth Univ, Richmond, VA USA. [Jha, Vivekanand] Postgrad Inst Med Educ & Res, Chandigarh 160012, India. [Jiang, Guohong] Tianjin Ctr Dis Control & Prevent, Tianjin, Peoples R China. [Jiang, Ying] Univ Occupat & Environm Hlth, Inst Ind Ecol Sci, Dept Hlth Dev, Dept Environm Epidemiol, Kitakyushu, Fukuoka 807, Japan. [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany. [Juel, Knud] Natl Inst Publ Hlth, Copenhagen, Denmark. [Kabagambe, Edmond Kato; Sampson, Uchechukwu] Vanderbilt Univ, Nashville, TN 37235 USA. Univ Balamand, Beirut, Lebanon. [Karch, Andre] Helmholtz Ctr Infect Res, Braunschweig, Germany. [Karch, Andre] German Ctr Infect Res DZIF, Braunschweig, Germany. [Karimkhani, Chante] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Moran, Andrew E.] Columbia Univ, New York, NY USA. [Karthikeyan, Ganesan; Paul, Vinod K.] All India Inst Med Sci, New Delhi, India. [Kaul, Anil] Oklahoma State Univ, Tulsa, OK USA. [Kengne, Andre Pascal; Matzopolous, Richard] South African Med Res Council, Cape Town, Western Cape, South Africa. [Keren, Andre] Hadassah Kerem Univ Hosp, Jerusalem, Israel. [Khader, Yousef Saleh] Jordan Univ Sci & Technol, Irbid, Jordan. [Khalifa, Shams Eldin Ali Hassan] Supreme Council Hlth, Doha, Qatar. [Khan, Ejaz Ahmed] Hlth Serv Acad, Islamabad, Punjab, Pakistan. [Khan, Gulfaraz] UAE Univ, Abu Dhabi, U Arab Emirates. [Khang, Young-Ho] Seoul Natl Univ, Coll Med, Inst Hlth Policy & Management, Seoul, South Korea. [Kieling, Christian] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil. [Kim, Daniel] Northeastern Univ, Boston, MA 02115 USA. [Kim, Sungroul] Soonchunhyang Univ, Asan, South Korea. [Kinfu, Yohannes] Univ Canberra, Canberra, ACT 2601, Australia. [Kokubo, Yoshihiro] Natl Cerebral & Cardiovasc Ctr, Dept Prevent Cardiol, Suita, Osaka, Japan. [Kosen, Sowarta] Ctr Community Empowerment Hlth Policy & Humanitie, Jakarta, Indonesia. [Warouw, Tati Suryati] NIHRD, Jakarta, Special Provinc, Indonesia. [Kravchenko, Michael A.; Varakin, Yuri Y.] Res Ctr Neurol, Moscow, Russia. [Krishnaswami, Sanjay] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Krishnaswami, Sanjay] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Defo, Barthelemy Kuate] Univ Montreal, Montreal, PQ, Canada. [Polinder, Suzanne] Dept Publ Hlth, Rotterdam, Netherlands. [Kuipers, Ernst J.; Richardus, Jan Hendrik] Erasmus MC Univ Med Ctr, Rotterdam, Netherlands. [Kulkarni, Chanda] Rajrajeshwari Med Coll & Hosp, Bangalore, Karnataka, India. [Kulkarni, Veena S.] Arkansas State Univ, State Univ, AR 72467 USA. [Kumar, Kaushalendra] Int Inst Populat Sci, Bombay, Maharashtra, India. [Kwan, Gene F.] Boston Med Ctr, Boston, MA USA. [Lai, Taavi] Fourth View Consulting, Tallinn, Estonia. [Lalloo, Ratilal] Australian Res Ctr Populat Oral Hlth, Gold Coast, Qld, Australia. [Lalloo, Ratilal] Univ Adelaide, Sch Dent, Gold Coast, Qld, Australia. [Lallukka, Tea] Finnish Inst Occupat Hlth, Helsinki, Finland. [Lallukka, Tea] Univ Helsinki, Fac Med, Hjelt Inst, FIN-00014 Helsinki, Finland. [Lan, Qing] NCI, Rockville, MD USA. [Lansingh, Van C.] IAPB & Vis 2020 LA, Weston, FL USA. [Lavados, Pablo M.] Univ Desarrollo, Serv Neurol Clin Alemana, Santiago, RM, Chile. [Lawrynowicz, Alicia E. B.; Silva, Andrea P.; Ubeda, Clotilde] Inst Nacl Epidemiol Dr Juan H Jara, Buenos Aires, DF, Argentina. [Leasher, Janet L.] Nova SE Univ, Ft Lauderdale, FL 33314 USA. [Lee, Jong-Tae; Yoon, Seok-Jun] Korea Univ, Seoul, South Korea. [Leung, Ricky] SUNY Albany, Rensselaer, NY USA. [Zhang, Yong] Dept Gerontol, Jinan, Shandong, Peoples R China. [Li, Bin] Jinan Cent Hosp, Jinan, Shandong, Peoples R China. [Li, Yichong] Genentech Inc, San Francisco, CA USA. [Lipshultz, Steven E.] Wayne State Univ, Miami, FL USA. [Lloyd, Belinda K.; Room, Robin] Eastern Hlth, Turning Point Alcohol & Drug Ctr, Fitzroy, Vic, Australia. [Logroscino, Giancarlo] Univ Bari, Bari, Italy. Australian Natl Univ, Canberra, ACT, Australia. [Lunevicius, Raimundas] Aintree Univ Hosp NHS Fdn Trust, NHS Fdn Trust, Liverpool L9 7AL, Merseyside, England. [Lyons, Ronan Anthony] Swansea Univ, swauni, Swansea, W Glam, Wales. [Ma, Stefan] Minist Hlth Singapore, Singapore, Singapore. [Mackay, Mark T.] Royal Childrens Hosp, Melbourne, Vic, Australia. [Magis-Rodriguez, Carlos] Ctr Prevenc & Control VIH SIDA, Mexico City, DF, Mexico. [Mahdi, Abbas A.] King Georges Med Univ, Lucknow, Uttar Pradesh, India. [Mangalam, Srikanth] Tech Stand & Safety Author, Toronto, ON, Canada. [Mapoma, Christopher Chabila; Masiye, Felix] Univ Zambia, Lusaka, Zambia. [Marape, Marape] Botswana Baylor Childrens Clin Ctr Excellence, Gaborone, Botswana. [Marcenes, Wagner] Univ London, London, England. 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Ryan/0000-0002-5485-7144; Khan, Ejaz/0000-0002-7072-8035; Hagstromer, Maria/0000-0002-4607-8677; Bikbov, Boris/0000-0002-1925-7506; MacLachlan, Jennifer/0000-0002-7654-4536; Gibney, Katherine/0000-0001-5851-5339; Stockl, Heidi/0000-0002-0907-8483; Kwan, Gene/0000-0002-0929-6800; Piel, Frederic B./0000-0001-8131-7728; Higashi, Hideki/0000-0002-5534-0905; Lavados, Pablo/0000-0002-9118-9093; Ukwaja, Kingsley N./0000-0002-1974-8735; Alsharif, Ubai/0000-0002-4024-3950; Amini, Heresh/0000-0002-4825-1322; Lotufo, Paulo/0000-0002-4856-8450; Karch, Andre/0000-0003-3014-8543; Hedayati, Mohammad T./0000-0001-6415-4648; Patten, Scott/0000-0001-9871-4041; Scott, James/0000-0002-0744-0688; Franklin, Richard/0000-0003-1864-4552; Ermakov, Sergey/0000-0003-1072-1162; Pereira, David/0000-0003-0384-7592; Bohensky, Megan/0000-0001-8370-1408; Montico, Marcella/0000-0003-0377-8232; Jacobsen, Kathryn/0000-0002-4198-6246; Lalloo, Ratilal/0000-0001-5822-1269; Tillmann, Taavi/0000-0002-8428-3719; Soshnikov, Sergey/0000-0002-6983-7066; Salomon, Joshua/0000-0003-3929-5515; Beyene, Tariku Jibat/0000-0002-7474-1966; Santos, Itamar/0000-0003-3212-8466; Patton, George/0000-0001-5039-8326; Brenner, Hermann/0000-0002-6129-1572; Whiteford, Harvey/0000-0003-4667-6623; Charlson, Fiona/0000-0003-2876-5040; Ronfani, Luca/0000-0001-5710-3914; LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Moffitt, Terrie/0000-0002-8589-6760; McGrath, John/0000-0002-4792-6068; Hankey, Graeme /0000-0002-6044-7328; wang, YA XING/0000-0003-2749-7793; Naldi, Luigi/0000-0002-3160-2835; Osborne, Nicholas/0000-0002-6700-2284; Thrift, Amanda/0000-0001-8533-4170; Weiderpass, Elisabete/0000-0003-2237-0128; Rahimi, Kazem/0000-0002-4807-4610; Haro, Josep Maria/0000-0002-3984-277X; Degenhardt, Louisa/0000-0002-8513-2218; Monasta, Lorenzo/0000-0001-7774-548X; Sepanlou, Sadaf/0000-0002-3669-5129; Kravchenko, Michael/0000-0001-5187-5518; Norheim, Ole F./0000-0002-5748-5956; London, Stephanie/0000-0003-4911-5290; Hay, Simon/0000-0002-0611-7272; Moradi-Lakeh, Maziar/0000-0001-7381-5305; NORMAN, ROSANA/0000-0002-9742-1957; Sindi, Shireen/0000-0002-3786-0552; Husseini, Abdullatif/0000-0001-8767-5956; Benjet, Corina/0000-0002-4569-6094; Al-Shahi Salman, Rustam/0000-0002-2108-9222; Prabhakaran, Dorairaj/0000-0002-3172-834X; Deribe, Kebede/0000-0002-8526-6996; Khang, Young-Ho/0000-0002-9585-8266; Ortiz Arduan, Alberto/0000-0002-9805-9523; Kemp, Andrew/0000-0003-1146-3791; Erskine, Holly/0000-0003-3119-9211; Heydarpour, Pouria/0000-0001-5644-7555; Soreide, Kjetil/0000-0001-7594-4354; Quistberg, Alex/0000-0001-9730-2686; Liu, Zhi-Hong/0000-0001-6093-0726; Kieling, Christian/0000-0001-7691-4149; Ribeiro, Antonio/0000-0002-2740-0042; Nolte, Sandra/0000-0001-6185-9423; Ameli, Omid/0000-0001-7878-0551; Rakovac, Ivo/0000-0003-3462-2636; Tanne, David/0000-0002-6699-2220; Adsuar, Jose C/0000-0001-7203-3168; Majdan, Marek/0000-0001-8037-742X; Aboyans, Victor/0000-0002-0322-9818; Brauer, Michael/0000-0002-9103-9343; Glaser, Elizabeth/0000-0002-1918-057X; Chen, Honglei/0000-0003-3446-7779; Perez-Ruiz, Fernando/0000-0002-5268-1894; Catala-Lopez, Ferran/0000-0002-3833-9312; Mhimbira, Francis/0000-0001-8989-6832; Olusanya, Bolajoko/0000-0002-3826-0583; Tabb Dina, Karen/0000-0002-4722-9502; Vallely, Andrew/0000-0003-1558-4822; Goenka, Shifalika/0000-0001-6993-2883; Xu, Gelin/0000-0002-6194-0341; Goto, Atsushi/0000-0003-0669-654X; Naghavi, Paria/0000-0002-8908-7952; Davis, Adrian/0000-0001-7134-7528; Banerjee, Amitava/0000-0001-8741-3411; Hotez, Peter/0000-0001-8770-1042; Abubakar, Ibrahim/0000-0002-0370-1430; Schottker, Ben/0000-0002-1217-4521; Pourmalek, Farshad/0000-0002-2134-0771; Undurraga, Eduardo/0000-0002-4425-1253 FU British Heart Foundation [RG/08/014/24067]; Department of Health [CDF-2013-06-012, RP-PG-0407-10184]; Medical Research Council [MC_U147585819, G9806489, MC_U137686851, MC_UP_A620_1014, MC_UU_12011/1, MR/K006525/1, MR/L003120/1]; NCATS NIH HHS [KL2 TR001088]; NIA NIH HHS [P30 AG017253]; NIEHS NIH HHS [P30 ES000260]; Wellcome Trust [089276, 089963, 099876] NR 122 TC 936 Z9 979 U1 221 U2 752 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JAN 10 PY 2015 VL 385 IS 9963 BP 117 EP 171 DI 10.1016/S0140-6736(14)61682-2 PG 55 WC Medicine, General & Internal SC General & Internal Medicine GA AY7BI UT WOS:000347715900024 PM 25530442 ER PT J AU Leak, RK Li, PY Zhang, F Sulaiman, HH Weng, ZF Wang, GH Stetler, RA Shi, YJ Cao, GD Gao, YQ Chen, J AF Leak, Rehana K. Li, Peiying Zhang, Feng Sulaiman, Hassan H. Weng, Zhongfang Wang, Guohua Stetler, R. Anne Shi, Yejie Cao, Guodong Gao, Yanqin Chen, Jun TI Apurinic/Apyrimidinic Endonuclease 1 Upregulation Reduces Oxidative DNA Damage and Protects Hippocampal Neurons from Ischemic Injury SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID BASE-EXCISION-REPAIR; GLOBAL CEREBRAL-ISCHEMIA; STRANDED DEOXYRIBONUCLEIC-ACID; CELLULAR STRESS RESPONSES; HUMAN ABASIC ENDONUCLEASE; TRANSIENT FOCAL ISCHEMIA; RAT-BRAIN; CRITICAL DETERMINANTS; SUPEROXIDE-DISMUTASE; IONIZING-RADIATION AB Aims: Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme that participates in base-excision repair of oxidative DNA damage and in the redox activation of transcription factors. We tested the hypothesis that APE1 upregulation protects neuronal structure and function against transient global cerebral ischemia (tGCI). Results: Upregulation of APE1 by low-dose proton irradiation (PI) or by transgene overexpression protected hippocampal CA1 neurons against tGCI-induced cell loss and reduced apurinic/apyrimidinic sites and DNA fragmentation. Conversely, APE1 knockdown attenuated the protection afforded by PI and ischemic preconditioning. APE1 overexpression inhibited the DNA damage response, as evidenced by lower phospho-histone H2A and p53-upregulated modulator of apoptosis levels. APE1 overexpression also partially rescued dendritic spines and attenuated the decrease in field excitatory postsynaptic potentials in hippocampal CA1. Presynaptic and postsynaptic markers were reduced after tGCI, and this effect was blunted in APE1 transgenics. The Morris water maze test revealed that APE1 protected against learning and memory deficits for at least 27 days post-injury. Animals expressing DNA repair-disabled mutant APE1 (D210A) exhibited more DNA damage than wild-type controls and were not protected against tGCI-induced cell loss. Innovation: This is the first study that thoroughly characterizes structural and functional protection against ischemia after APE1 upregulation by measuring synaptic markers, electrophysiological function, and long-term neurological deficits in vivo. Furthermore, disabling the DNA repair activity of APE1 was found to abrogate its protective impact. Conclusion: APE1 upregulation, either endogenously or through transgene overexpression, protects DNA, neuronal structures, synaptic function, and behavioral output from ischemic injury. Antioxid. Redox Signal. 22, 135-148. C1 [Leak, Rehana K.; Li, Peiying; Zhang, Feng; Wang, Guohua; Stetler, R. Anne; Cao, Guodong; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Leak, Rehana K.; Li, Peiying; Zhang, Feng; Wang, Guohua; Stetler, R. Anne; Cao, Guodong; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Leak, Rehana K.; Li, Peiying; Zhang, Feng; Sulaiman, Hassan H.; Weng, Zhongfang; Wang, Guohua; Stetler, R. Anne; Shi, Yejie; Cao, Guodong; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA USA. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA. [Leak, Rehana K.; Li, Peiying; Zhang, Feng; Sulaiman, Hassan H.; Weng, Zhongfang; Stetler, R. Anne; Shi, Yejie; Cao, Guodong; Chen, Jun] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Zhang, Feng; Weng, Zhongfang; Stetler, R. Anne; Cao, Guodong; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Dept Neurol, S507 Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM yqgao@shmu.edu.cn; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417; Shi, Yejie/0000-0001-7502-9201 FU NIH [NS036736, NS043802, NS045048]; AHA [10SDG2560122]; Chinese Natural Science Foundation [30870794, 81020108021, 81171149, 81371306, 81228008]; VA; UPMC FX These studies were supported by NIH grants NS036736, NS043802, and NS045048 (to J.C.) and AHA grant 10SDG2560122 (to F.Z.). Y.G. was supported by Chinese Natural Science Foundation grant numbers 30870794, 81020108021, 81171149, and 81371306. J.C. is the recipient of the Research Career Scientist award from the VA and of the Richard King Mellon Endowed Professorship from UPMC and was also supported by Chinese Natural Science Foundation grant number 81228008. The authors are indebted to Pat Strickler for outstanding administrative support. NR 67 TC 5 Z9 6 U1 1 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN 10 PY 2015 VL 22 IS 2 BP 135 EP 148 DI 10.1089/ars.2013.5511 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AX6NC UT WOS:000347037800004 PM 24180454 ER PT J AU Brennan-Minnella, AM Won, SJ Swanson, RA AF Brennan-Minnella, Angela M. Won, Seok Joon Swanson, Raymond A. TI NADPH Oxidase-2: Linking Glucose, Acidosis, and Excitotoxicity in Stroke SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID METHYL-D-ASPARTATE; CYTOSOLIC PHOSPHOLIPASE A(2); FOCAL CEREBRAL-ISCHEMIA; NMDA RECEPTOR ACTIVATION; TISSUE-PLASMINOGEN ACTIVATOR; KINASE-C-ZETA; NEUTROPHIL RESPIRATORY BURST; CEREBELLAR GRANULE CELLS; EXCITATORY AMINO-ACIDS; REACTIVE-OXYGEN AB Significance: Neuronal superoxide production contributes to cell death in both glutamate excitotoxicity and brain ischemia (stroke). NADPH oxidase-2 (NOX2) is the major source of neuronal superoxide production in these settings, and regulation of NOX2 activity can thereby influence outcome in stroke. Recent Advances: Reduced NOX2 activity can rescue cells from oxidative stress and cell death that otherwise occur in excitotoxicity and ischemia. NOX2 activity is regulated by several factors previously shown to affect outcome in stroke, including glucose availability, intracellular pH, protein kinase zeta/delta, casein kinase 2, phosphoinositide-3-kinase, Rac1/2, and phospholipase A2. The newly identified functions of these factors as regulators of NOX2 activity suggest alternative mechanisms for their effects on ischemic brain injury. Critical Issues: Key aspects of these regulatory influences remain unresolved, including the mechanisms by which rac1 and phospholipase activities are coupled to N-methyl-D-aspartate (NMDA) receptors, and whether superoxide production by NOX2 triggers subsequent superoxide production by mitochondria. Future Directions: It will be important to establish whether interventions targeting the signaling pathways linking NMDA receptors to NOX2 in brain ischemia can provide a greater neuroprotective efficacy or a longer time window to treatment than provided by NMDA receptor blockade alone. It will likewise be important to determine whether dissociating superoxide production from the other signaling events initiated by NMDA receptors can mitigate the deleterious effects of NMDA receptor blockade. Antioxid. Redox Signal. 22, 161-174. C1 [Brennan-Minnella, Angela M.; Won, Seok Joon; Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Brennan-Minnella, Angela M.; Won, Seok Joon; Swanson, Raymond A.] San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA USA. RP Swanson, RA (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. EM raymond.swanson@ucsf.edu OI Swanson, Raymond/0000-0002-3664-5359 FU U.S. Dept. of Veterans Affairs; National Institutes of Health [NS081149] FX This work was supported by the U.S. Dept. of Veterans Affairs and National Institutes of Health (grant NS081149). We thank Colleen Hefner for assistance with the article preparation. NR 196 TC 9 Z9 9 U1 3 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN 10 PY 2015 VL 22 IS 2 BP 161 EP 174 DI 10.1089/ars.2013.5767 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AX6NC UT WOS:000347037800006 PM 24628477 ER PT J AU Giuliano, M Herrera, S Christiny, P Shaw, C Creighton, CJ Mitchell, T Bhat, R Zhang, XM Mao, SF Dobrolecki, LE Al-Rawi, A Chen, FJ Veneziani, BM Zhang, XHF Hilsenbeck, SG Contreras, A Gutierrez, C Jeselsohn, RM Rimawi, MF Osborne, CK Lewis, MT Schiff, R Trivedi, MV AF Giuliano, Mario Herrera, Sabrina Christiny, Pavel Shaw, Chad Creighton, Chad J. Mitchell, Tamika Bhat, Raksha Zhang, Xiaomei Mao, Sufeng Dobrolecki, Lacey E. Al-Rawi, Ahmed Chen, Fengju Veneziani, Bianca M. Zhang, Xiang H-F Hilsenbeck, Susan G. Contreras, Alejandro Gutierrez, Carolina Jeselsohn, Rinath M. Rimawi, Mothaffar F. Osborne, C. Kent Lewis, Michael T. Schiff, Rachel Trivedi, Meghana V. TI Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis SO BREAST CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; PERIPHERAL-BLOOD; BONE-MARROW; POOLED ANALYSIS; STEM-CELL; SURVIVAL; MARKERS; THERAPY; PROGRESSION; EXPRESSION AB Introduction: Real-time monitoring of biologic changes in tumors may be possible by investigating the transitional cells such as circulating tumor cells (CTCs) and disseminated tumor cells in bone marrow (BM-DTCs). However, the small numbers of CTCs and the limited access to bone marrow aspirates in cancer patients pose major hurdles. The goal of this study was to determine whether breast cancer (BC) patient-derived xenograft (PDX) mice could provide a constant and renewable source of CTCs and BM-DTCs, thereby representing a unique system for the study of metastatic processes. Methods: CTCs and BM-DTCs, isolated from BC PDX-bearing mice, were identified by immunostaining for human pan-cytokeratin and nuclear counterstaining of red blood cell-lysed blood and bone marrow fractions, respectively. The rate of lung metastases (LM) was previously reported in these lines. Associations between the presence of CTCs, BM-DTCs, and LM were assessed by the Fisher's Exact and Cochran-Mantel-Haenszel tests. Two separate genetic signatures associated with the presence of CTC clusters and with lung metastatic potential were computed by using the expression arrays of primary tumors from different PDX lines and subsequently overlapped to identify common genes. Results: In total, 18 BC PDX lines were evaluated. CTCs and BM-DTCs, present as either single cells or clusters, were detected in 83% (15 of 18) and 62.5% (10 to 16) of the lines, respectively. A positive association was noted between the presence of CTCs and BM-DTCs within the same mice. LM was previously found in 9 of 18 (50%) lines, of which all nine had detectable CTCs. The presence of LM was strongly associated with the detection of CTC clusters but not with individual cells or detection of BM-DTCs. Overlapping of the two genetic signatures of the primary PDX tumors associated with the presence of CTC clusters and with lung metastatic potential identified four genes (HLA-DP1A, GJA1, PEG3, and XIST). This four-gene profile predicted distant metastases-free survival in publicly available datasets of early BC patients. Conclusion: This study suggests that CTCs and BM-DTCs detected in BC PDX-bearing mice may represent a valuable and unique preclinical model for investigating the role of these rare cells in tumor metastases. C1 [Giuliano, Mario; Herrera, Sabrina; Mitchell, Tamika; Zhang, Xiaomei; Mao, Sufeng; Dobrolecki, Lacey E.; Zhang, Xiang H-F; Hilsenbeck, Susan G.; Contreras, Alejandro; Gutierrez, Carolina; Jeselsohn, Rinath M.; Rimawi, Mothaffar F.; Osborne, C. Kent; Lewis, Michael T.; Schiff, Rachel; Trivedi, Meghana V.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Giuliano, Mario] Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy. [Christiny, Pavel; Bhat, Raksha; Al-Rawi, Ahmed; Trivedi, Meghana V.] Univ Houston, Dept Pharm Practice & Translat Res, Houston, TX USA. [Shaw, Chad; Creighton, Chad J.; Chen, Fengju; Zhang, Xiang H-F; Hilsenbeck, Susan G.; Contreras, Alejandro; Gutierrez, Carolina; Rimawi, Mothaffar F.; Osborne, C. Kent; Lewis, Michael T.; Schiff, Rachel; Trivedi, Meghana V.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Shaw, Chad] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Creighton, Chad J.; Zhang, Xiang H-F; Hilsenbeck, Susan G.; Rimawi, Mothaffar F.; Osborne, C. Kent; Schiff, Rachel; Trivedi, Meghana V.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Veneziani, Bianca M.] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy. [Zhang, Xiang H-F; Schiff, Rachel] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Contreras, Alejandro; Gutierrez, Carolina] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Jeselsohn, Rinath M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lewis, Michael T.] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. [Trivedi, Meghana V.] Univ Houston, Dept Pharmacol & Pharmaceut Sci, Houston, TX USA. RP Schiff, R (reprint author), Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. EM rschiff@bcm.edu; mtrivedi@UH.EDU RI Veneziani, Bianca/R-4791-2016; OI VENEZIANI, Bianca Maria/0000-0002-1678-4183 FU National Institutes of Health [U54CA149196, P01 SPORE]; faculty start-up funds; Cancer Prevention and Research Institute of Texas (CPRIT) program [RP101499]; Baylor College of Medicine Comprehensive Cancer Training Program; Susan G. Komen grant [KG120001]; Dan L. Duncan Cancer Center Grant from the National Cancer Institute, Cytometry and Cell Sorting Core at Baylor College of Medicine [P30CA125123]; NIH [P30 AI036211, P30 CA125123, S10 RR024574]; Breast Cancer Research Foundation; Entertainment Industry Foundation/Lee Jeans; SU2C Breast Cancer Program FX This study was supported in part by National Institutes of Health grants U54CA149196 (to R.S. and M.T.); P01 SPORE (to R.S. and R.M.J.); faculty start-up funds (to M.T.); Cancer Prevention and Research Institute of Texas (CPRIT) program RP101499, Baylor College of Medicine Comprehensive Cancer Training Program (to M.G.); Susan G. Komen grant KG120001 (to M.L.); Dan L. Duncan Cancer Center Grant P30CA125123 from the National Cancer Institute, Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the NIH (P30 AI036211, P30 CA125123, and S10 RR024574), research grants from the Breast Cancer Research Foundation; the Entertainment Industry Foundation/Lee Jeans, and SU2C Breast Cancer Program. We also acknowledge the following Baylor College of Medicine shared resources: Biostatistics & Informatics; Cytometry and Cell Sorting; and Human Tissue Acquisition and Pathology. NR 49 TC 9 Z9 10 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PD JAN 9 PY 2015 VL 17 AR 3 DI 10.1186/s13058-014-0508-5 PG 9 WC Oncology SC Oncology GA CE3JR UT WOS:000351723100002 PM 25572662 ER PT J AU Kuo, AH Ancukiewicz, M Kozak, KR Yock, TI Padera, TP AF Kuo, Angera H. Ancukiewicz, Marek Kozak, Kevin R. Yock, Torunn I. Padera, Timothy P. TI Cardiac and inflammatory biomarkers do not correlate with volume of heart or lung receiving radiation SO RADIATION ONCOLOGY LA English DT Article DE Radiation; Lung cancer; Cardiotoxicity; Radiation induced pneumonitis; Biomarkers; C-reactive protein ID POSTOPERATIVE RADIOTHERAPY; PROTEIN; CANCER; SERUM; PNEUMONITIS AB Background: Thoracic and cardiac irradiation increases the risk of pulmonary and cardiovascular disease. In addition, radiation, often in combination with chemotherapy, can cause treatment-related pneumonitis. Previously, we showed that the common marker for cardiac damage, troponin T, was not elevated by chemoradiation [Lung Cancer 62:351-355, 2008]. In this study, we explore whether dose-volume metrics and biomarkers for cardiac damage, inflammation or angiogenesis could identify patients receiving thoracic radiation who would later have cardiac or pulmonary complications. Findings: To this end, we quantified cardiac biomarkers including c-reactive protein (cRP) as well as a panel of angiogenic and inflammatory molecules in thirty patients who received radiation therapy to the thorax with or without concurrent chemotherapy between May 2006 and May 2007. Serum was collected at baseline, 2 weeks into radiation treatment and at the completion of radiation therapy. Heart and lung dosimetric parameters and clinical risk factors were also examined, along with the monitoring of adverse pulmonary and cardiac events during follow-up. Contrary to our hypothesis, there was no correlation between serum biomarker levels and cardiac radiation dose. Similarly there was little association between lung dose-volume metrics and inflammatory or angiogenic biomarkers. Furthermore, there was no correlation with serum biomarkers and adverse pulmonary or cardiovascular events. Conclusion: Based on these data, acute elevations in serum biomarkers of cardiac damage, inflammation or angiogenesis should not be attributed to thoracic (chemo) radiation and elevations in such biomarkers of tissue damage should be further evaluated. C1 [Kuo, Angera H.; Ancukiewicz, Marek; Kozak, Kevin R.; Yock, Torunn I.; Padera, Timothy P.] Massachusetts Gen Hosp, MGH Canc Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. [Kuo, Angera H.; Ancukiewicz, Marek; Kozak, Kevin R.; Yock, Torunn I.; Padera, Timothy P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Padera, TP (reprint author), Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. EM tpadera@steele.mgh.harvard.edu OI Padera, Timothy/0000-0002-3453-9384 FU Ira J. Spiro Translational Research Award; NIH [R00CA137167, DP2OD008780] FX We thank Anna Khachatryan for her outstanding technical support. This work was supported by an Ira J. Spiro Translational Research Award (TIY, TPP), NIH R00CA137167 (TPP) and NIH DP2OD008780 (TPP). NR 13 TC 5 Z9 5 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-717X J9 RADIAT ONCOL JI Radiat. Oncol. PD JAN 9 PY 2015 VL 10 AR 5 DI 10.1186/s13014-014-0324-1 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CA9ZA UT WOS:000349283100001 PM 25573181 ER PT J AU Konadhode, RR Pelluru, D Shiromani, PJ AF Konadhode, Roda Rani Pelluru, Dheeraj Shiromani, Priyattam J. TI Neurons containing orexin or melanin concentrating hormone reciprocally regulate wake and sleep SO FRONTIERS IN SYSTEMS NEUROSCIENCE LA English DT Article DE sleep; melanin concentrating hormone; optogenetics; hypothalamus ID EYE-MOVEMENT SLEEP; VENTROLATERAL PREOPTIC NUCLEUS; LATERAL HYPOTHALAMIC AREA; WAKING DISCHARGE PATTERNS; LOCUS-COERULEUS NEURONS; SLOW-WAVE SLEEP; REM-SLEEP; MCH NEURONS; KNOCKOUT MICE; GENE-TRANSFER AB Neurons containing orexin (hypocretin), or melanin concentrating hormone (MCH) are intermingled with each other in the perifornical and lateral hypothalamus. Each is a separate and distinct neuronal population, but they project to similar target areas in the brain. Orexin has been implicated in regulating arousal since loss of orexin neurons is associated with the sleep disorder narcolepsy. Microinjections of orexin into the brain or optogenetic stimulation of orexin neurons increase waking. Orexin neurons are active in waking and quiescent in sleep, which is consistent with their role in promoting waking. On the other hand, the MCH neurons are quiet in waking but active in sleep, suggesting that they could initiate sleep. Recently, for the first time the MCH neurons were stimulated optogenetically and it increased sleep. Indeed, optogenetic activation of MCH neurons induced sleep in both mice and rats at a circadian time when they should be awake, indicating the powerful effect that MCH neurons have in suppressing the wake-promoting effect of not only orexin but also of all of the other arousal neurotransmitters. Gamma-Aminobutyric acid (GABA) is coexpressed with MCH in the MCH neurons, although MCH is also inhibitory. The inhibitory tone of the MCH neurons is opposite to the excitatory tone of the orexin neurons. We hypothesize that strength in activity of each determines wake vs. sleep. C1 [Konadhode, Roda Rani; Pelluru, Dheeraj; Shiromani, Priyattam J.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Konadhode, Roda Rani; Pelluru, Dheeraj; Shiromani, Priyattam J.] Med Univ S Carolina, Dept Behav Sci, Charleston, SC 29425 USA. [Shiromani, Priyattam J.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Shiromani, PJ (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, 114 Doughty St,Room 404, Charleston, SC 29425 USA. EM shiroman@musc.edu NR 101 TC 6 Z9 6 U1 2 U2 6 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5137 J9 FRONT SYST NEUROSCI JI Front. Syst. Neurosci. PD JAN 8 PY 2015 VL 8 AR UNSP 244 DI 10.3389/fnsys.2014.00244 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CU6SM UT WOS:000363663800001 ER PT J AU McCarthy, AM Keller, B Kontos, D Boghossian, L McGuire, E Bristol, M Chen, JB Domchek, S Armstrong, K AF McCarthy, Anne Marie Keller, Brad Kontos, Despina Boghossian, Leigh McGuire, Erin Bristol, Mirar Chen, Jinbo Domchek, Susan Armstrong, Katrina TI The use of the Gail model, body mass index and SNPs to predict breast cancer among women with abnormal (BI-RADS 4) mammograms SO BREAST CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; AFRICAN-AMERICAN WOMEN; SUSCEPTIBILITY LOCI; RISK PREDICTION; DATA SYSTEM; SCREENING MAMMOGRAPHY; CONFER SUSCEPTIBILITY; GENETIC-VARIANTS; COMMON VARIANTS AB Introduction: Mammography screening results in a significant number of false-positives. The use of pretest breast cancer risk factors to guide follow-up of abnormal mammograms could improve the positive predictive value of screening. We evaluated the use of the Gail model, body mass index (BMI), and genetic markers to predict cancer diagnosis among women with abnormal mammograms. We also examined the extent to which pretest risk factors could reclassify women without cancer below the biopsy threshold. Methods: We recruited a prospective cohort of women referred for biopsy with abnormal (BI-RADS 4) mammograms according to the American College of Radiology's Breast Imaging-Reporting and Data System (BI-RADS). Breast cancer risk factors were assessed prior to biopsy. A validated panel of 12 single-nucleotide polymorphisms (SNPs) associated with breast cancer were measured. Logistic regression was used to assess the association of Gail risk factors, BMI and SNPs with cancer diagnosis (invasive or ductal carcinoma in situ). Model discrimination was assessed using the area under the receiver operating characteristic curve, and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. The distribution of predicted probabilities of a cancer diagnosis were compared for women with or without breast cancer. Results: In the multivariate model, age (odds ratio (OR) = 1.05; 95% confidence interval (CI), 1.03 to 1.08; P < 0.001), SNP panel relative risk (OR = 2.30; 95% CI, 1.06 to 4.99, P = 0.035) and BMI (>= 30 kg/m(2) versus < 25 kg/m(2); OR = 2.20; 95% CI, 1.05 to 4.58; P = 0.036) were significantly associated with breast cancer diagnosis. Older women were more likely than younger women to be diagnosed with breast cancer. The SNP panel relative risk remained strongly associated with breast cancer diagnosis after multivariable adjustment. Higher BMI was also strongly associated with increased odds of a breast cancer diagnosis. Obese women (OR = 2.20; 95% CI, 1.05 to 4.58; P = 0.036) had more than twice the odds of cancer diagnosis compared to women with a BMI < 25 kg/m(2). The SNP panel appeared to have predictive ability among both white and black women. Conclusions: Breast cancer risk factors, including BMI and genetic markers, are predictive of cancer diagnosis among women with BI-RADS 4 mammograms. Using pretest risk factors to guide follow-up of abnormal mammograms could reduce the burden of false-positive mammograms. C1 [McCarthy, Anne Marie; Bristol, Mirar; Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Keller, Brad; Kontos, Despina] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Boghossian, Leigh; Domchek, Susan] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [McGuire, Erin] Univ Penn, Dept Gen Internal Med, Philadelphia, PA 19104 USA. [Chen, Jinbo] Univ Penn, Dept Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP McCarthy, AM (reprint author), Massachusetts Gen Hosp, Dept Med, 50 Staniford St,940F, Boston, MA 02114 USA. EM amccarthy8@partners.org FU National Institutes of Health, National Cancer Institute (NIH/NCI) [P01 CA85484, UC2 CA148310, U54 CA163313]; NCI [R01 CA164305] FX This work was supported by the following grants from the National Institutes of Health, National Cancer Institute (NIH/NCI): P01 CA85484, UC2 CA148310 and U54 CA163313. Additionally, JC was partially supported by NCI award R01 CA164305. The NIH/NCI did not have any role in the study design; collection, analysis or interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication. NR 69 TC 4 Z9 6 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PD JAN 8 PY 2015 VL 17 AR 1 DI 10.1186/s13058-014-0509-4 PG 10 WC Oncology SC Oncology GA CE3JO UT WOS:000351722800001 PM 25567532 ER PT J AU Sauna, ZE Lozier, JN Kasper, CK Yanover, C Nichols, T Howard, TE AF Sauna, Zuben E. Lozier, Jay N. Kasper, Carol K. Yanover, Chen Nichols, Timothy Howard, Tom E. TI The intron-22-inverted F8 locus permits factor VIII synthesis: explanation for low inhibitor risk and a role for pharmacogenomics SO BLOOD LA English DT Article ID SEVERE HEMOPHILIA-A; ENDOGENOUS FACTOR-VIII; MHC CLASS-II; CENTRAL TOLERANCE; GENE; MUTATION; MILD; CELLS; IMMUNOGENICITY; INVERSIONS AB Intron-22-inversion patients express the entire Factor VIII (FVIII)-amino-acid sequence intracellularly as 2 non-secreted polypeptides and have a positive "intracellular (I)-FVIII-CRM" status. Mutations conferring a positive I-FVIII-CRM status are associated with low inhibitor risk and are pharmacogenetically relevant because inhibitor risk may be affected by the nature of the therapeutic FVIII-protein (tFVIII), the affinity of any tFVIII-derived foreign peptide (tFVIII-fp) for anyHLAclass-II isomer (HLA-II) comprising individual major histocompatibility complex (MHC) repertoires, and the stability of any tFVIII-fp/HLA-II complex. We hypothesize that mutations conferring a completely or substantially negative I-FVIII-CRM status are pharmacogenetically irrelevant because inhibitor risk is high with any tFVIII and individual MHC repertoire. C1 [Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA. [Lozier, Jay N.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Kasper, Carol K.] Orthopaed Hemophilia Treatment Ctr, Los Angeles, CA USA. [Kasper, Carol K.] Univ So Calif, Keck Sch Med, Dept Med, Div Hematol, Los Angeles, CA 90033 USA. [Yanover, Chen] IBM Res Lab, Machine Learning Healthcare & Life Sci, Haifa, Israel. [Nichols, Timothy] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Nichols, Timothy] Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. [Howard, Tom E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Howard, Tom E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. RP Howard, TE (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Bldg 500,Room 1258, Los Angeles, CA 90073 USA. EM zuben.sauna@fda.hhs.gov; Tom.Howard@va.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 FU Modernization of Science Program of the Center for Biologics Evaluation and Research, United States Food and Drug Administration; National Heart, Lung and Blood Institute, National Institutes of Health [1RC2-HL101851, HL-71130, HL-72533]; Bayer Healthcare Corporation; Bayer Hemophilia Awards Program; Baxter Healthcare Corporation; Clinical Translational Science Institute at the University of Southern California FX This study was supported by the Modernization of Science Program of the Center for Biologics Evaluation and Research, United States Food and Drug Administration (Z.E.S.); and grants from the National Heart, Lung and Blood Institute, National Institutes of Health (1RC2-HL101851, HL-71130, HL-72533), the Bayer Healthcare Corporation, Bayer Hemophilia Awards Program, Baxter Healthcare Corporation, and the Clinical Translational Science Institute at the University of Southern California (T.E.H.). NR 31 TC 3 Z9 4 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 8 PY 2015 VL 125 IS 2 BP 223 EP 228 DI 10.1182/blood-2013-12-530113 PG 6 WC Hematology SC Hematology GA CD1CA UT WOS:000350810200010 PM 25406352 ER PT J AU Janiszewska, M Polyak, K AF Janiszewska, Michalina Polyak, Kornelia TI Clonal Evolution in Cancer: A Tale of Twisted Twines SO CELL STEM CELL LA English DT Editorial Material ID MODEL AB Intra-tumor heterogeneity of cancer cells hampers the design of effective therapies and yet it is poorly reproduced in experimental models. A recent report by Eirew at al. provides an in-depth analysis of genetic heterogeneity of breast tumor xenografts and shows that changes in clonal diversity might not be stochastic. C1 [Janiszewska, Michalina; Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Janiszewska, Michalina; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Polyak, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM kornelia_polyak@dfci.harvard.edu NR 8 TC 7 Z9 7 U1 1 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD JAN 8 PY 2015 VL 16 IS 1 BP 11 EP 12 DI 10.1016/j.stem.2014.12.011 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AY6YK UT WOS:000347708400006 PM 25575078 ER PT J AU Tan, L Nomanbhoy, T Gurbani, D Patricelli, M Hunter, J Geng, JF Herhaus, L Zhang, JM Pauls, E Ham, Y Choi, HG Xie, T Deng, XM Buhrlage, SJ Sim, T Cohen, P Sapkota, G Westover, KD Gray, NS AF Tan, Li Nomanbhoy, Tyzoon Gurbani, Deepak Patricelli, Matthew Hunter, John Geng, Jiefei Herhaus, Lina Zhang, Jianming Pauls, Eduardo Ham, Youngjin Choi, Hwan Geun Xie, Ting Deng, Xianming Buhrlage, Sara J. Sim, Taebo Cohen, Philip Sapkota, Gopal Westover, Kenneth D. Gray, Nathanael S. TI Discovery of Type II Inhibitors of TGF beta-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RESORCYLIC ACID LACTONE; INDUCED APOPTOSIS; CELLS; OPTIMIZATION; RESISTANCE; PLATFORM; INNATE; MODEL; JNK AB We developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38a (MAPK14) and ABL. Further investigation of the structureactivity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16 and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. A 2.4 angstrom cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors. C1 [Tan, Li; Zhang, Jianming; Ham, Youngjin; Choi, Hwan Geun; Xie, Ting; Deng, Xianming; Buhrlage, Sara J.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Tan, Li; Zhang, Jianming; Ham, Youngjin; Xie, Ting; Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Nomanbhoy, Tyzoon; Patricelli, Matthew] ActivX Biosci, La Jolla, CA 92037 USA. [Gurbani, Deepak; Hunter, John; Westover, Kenneth D.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Gurbani, Deepak; Hunter, John; Westover, Kenneth D.] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA. [Geng, Jiefei] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Herhaus, Lina; Pauls, Eduardo; Cohen, Philip; Sapkota, Gopal] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat & Ubiquitylat Unit, Dundee DD1 5EH, Scotland. [Sim, Taebo] Korea Inst Sci & Technol, Chem Kinom Res Ctr, Seoul 136791, South Korea. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM nathanael_gray@dfci.harvard.edu FU NIH [CA130876-05, HG006097-03, CPRIT R1207]; U.S. Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357] FX This study was supported by research funding from NIH Grants CA130876-05 (N.S.G.), HG006097-03 (N.S.G), and CPRIT R1207 (K.D.W.). We thank Diana Tomchick, Zhe Chen, and the staff at the structural biology laboratory at UT Southwestern Medical Center and beamline 19ID for assistance with X-ray data collection and processing. Results shown in this report are derived from work performed at Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. Argonne is operated by UChicago Argonne, LLC, for the U.S. Department of Energy, Office of Biological and Environmental Research under Contract DE-AC02-06CH11357. The Gen2.2 cells used in this study were generously provided by Dr. Joel Plumas and Dr. Laurence Chaperot. We thank Dr. Ying Li for her suggestions and help for this study. NR 32 TC 12 Z9 12 U1 4 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD JAN 8 PY 2015 VL 58 IS 1 SI SI BP 183 EP 196 DI 10.1021/jm500480k PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AY7MH UT WOS:000347743700011 PM 25075558 ER PT J AU Lunt, SY Muralidhar, V Hosios, AM Israelsen, WJ Gui, DY Newhouse, L Ogrodzinski, M Hecht, V Xu, K Acevedo, PNM Hollern, DP Bellinger, G Dayton, TL Christen, S Elia, I Dinh, AT Stephanopoulos, G Manalis, SR Yaffe, MB Andrechek, ER Fendt, SM Vander Heiden, MG AF Lunt, Sophia Y. Muralidhar, Vinayak Hosios, Aaron M. Israelsen, William J. Gui, Dan Y. Newhouse, Lauren Ogrodzinski, Martin Hecht, Vivian Xu, Kali Acevedo, Paula N. Marin Hollern, Daniel P. Bellinger, Gary Dayton, Talya L. Christen, Stefan Elia, Ilaria Dinh, Anh T. Stephanopoulos, Gregory Manalis, Scott R. Yaffe, Michael B. Andrechek, Eran R. Fendt, Sarah-Maria Vander Heiden, Matthew G. TI Pyruvate Kinase Isoform Expression Alters Nucleotide Synthesis to Impact Cell Proliferation SO MOLECULAR CELL LA English DT Article ID REDUCTIVE GLUTAMINE-METABOLISM; TUMOR-CELLS; GENE-TRANSCRIPTION; CANCER METABOLISM; CYCLE PROGRESSION; PROTEIN-KINASE; M2; PKM2; PROMOTES; METHOTREXATE AB Metabolic regulation influences cell proliferation. The influence of pyruvate kinase isoforms on tumor cells has been extensively studied, but whether PKM2 is required for normal cell proliferation is unknown. We examine how PKM2 deletion affects proliferation and metabolism in nontransformed, nonimmortalized PKM2-expressing primary cells. We find that deletion of PKM2 in primary cells results in PKM1 expression and proliferation arrest. PKM1 expression, rather than PKM2 loss, is responsible for this effect, and proliferation arrest cannot be explained by cell differentiation, senescence, death, changes in gene expression, or prevention of cell growth. Instead, PKM1 expression impairs nucleotide production and the ability to synthesize DNA and progress through the cell cycle. Nucleotide biosynthesis is limiting, as proliferation arrest is characterized by severe thymidine depletion, and supplying exogenous thymine rescues both nucleotide levels and cell proliferation. Thus, PKM1 expression promotes a metabolic state that is unable to support DNA synthesis. C1 [Lunt, Sophia Y.; Muralidhar, Vinayak; Hosios, Aaron M.; Israelsen, William J.; Gui, Dan Y.; Hecht, Vivian; Xu, Kali; Acevedo, Paula N. Marin; Bellinger, Gary; Dayton, Talya L.; Dinh, Anh T.; Manalis, Scott R.; Yaffe, Michael B.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Lunt, Sophia Y.; Newhouse, Lauren; Ogrodzinski, Martin; Hollern, Daniel P.; Andrechek, Eran R.] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA. [Muralidhar, Vinayak] Harvard Univ, Sch Med, Harvard MIT Hlth Sci & Technol Div, Boston, MA 02115 USA. [Hosios, Aaron M.; Israelsen, William J.; Gui, Dan Y.; Dayton, Talya L.; Yaffe, Michael B.; Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Ogrodzinski, Martin] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Hecht, Vivian; Manalis, Scott R.; Yaffe, Michael B.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Christen, Stefan; Elia, Ilaria; Fendt, Sarah-Maria] VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium. [Christen, Stefan; Elia, Ilaria; Fendt, Sarah-Maria] Katholieke Univ Leuven, Dept Oncol, B-3000 Leuven, Belgium. [Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 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 Lunt, Sophia/0000-0003-4522-6065; Fendt, Sarah-Maria/0000-0001-6018-9296 FU Department of Defense CDMRP Visionary Postdoctoral Award [W81XWH-12-1-0466]; Marie Curie CIG; FWO-Odysseus II; Concern Foundation funding; Bayer Healthcare Pharmaceuticals; Smith Family Foundation; Burroughs Wellcome Fund; Damon Runyon Cancer Research Foundation; Stern family; American Association for Cancer Research; National Cancer Institute, NIH [5P30CA1405141, R01CA168653] FX This research was supported by the Department of Defense CDMRP Visionary Postdoctoral Award under award number (W81XWH-12-1-0466) to S.Y.L. The work of S.-M.F. was supported by Marie Curie CIG, FWO-Odysseus II, Concern Foundation funding, and Bayer Healthcare Pharmaceuticals. This work was also supported by the Smith Family Foundation, the Burroughs Wellcome Fund, the Damon Runyon Cancer Research Foundation, the Stern family, the American Association for Cancer Research, and the National Cancer Institute including NIH 5P30CA1405141 and R01CA168653. The authors thank Gavin Reid and Julia Busik for access to their laboratories; Stephanie Yazinski for experimental advice; Alice Chen, Amy Liu, Olivia Czajkowski, Jordan Honeysett, Michael Monterey, Jon Rennhack, Eric Poliner, Blair Bullard, Christoph Benning, and the Koch Institute Swanson Biotechnology Center for technical assistance; Craig Thomas and Matthew Boxer for providing PKM2 activators; and Christian Metallo, Eric Bell, Ben Olenchock, Caroline Lewis, Brian Fiske, Katie Mattaini, Shawn Davidson, Jared Mayers, Amelia Yu, and Zach Johnson for thoughtful discussions and comments on the manuscript. M.G.V.H. is a consultant and advisory board member for Agios Pharmaceuticals. NR 78 TC 39 Z9 40 U1 1 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD JAN 8 PY 2015 VL 57 IS 1 BP 95 EP 107 DI 10.1016/j.molcel.2014.10.027 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AY6ZM UT WOS:000347711100009 PM 25482511 ER PT J AU Ouyang, J Garner, E Hallet, A Nguyen, HD Rickman, KA Gill, G Smogorzewska, A Zou, L AF Ouyang, Jian Garner, Elizabeth Hallet, Alexander Hai Dang Nguyen Rickman, Kimberly A. Gill, Grace Smogorzewska, Agata Zou, Lee TI Noncovalent Interactions with SUMO and Ubiquitin Orchestrate Distinct Functions of the SLX4 Complex in Genome Maintenance SO MOLECULAR CELL LA English DT Article ID HOLLIDAY JUNCTION RESOLUTION; DOUBLE-STRAND BREAKS; CROSS-LINK REPAIR; STRUCTURE-SPECIFIC ENDONUCLEASES; STRUCTURE-SPECIFIC NUCLEASES; REPLICATION FORK COLLAPSE; DNA-DAMAGE RESPONSE; FANCONI-ANEMIA; HUMAN-CELLS; E3 LIGASE AB SLX4, a coordinator of multiple DNA structure-specific endonucleases, is important for several DNA repair pathways. Noncovalent interactions of SLX4 with ubiquitin are required for localizing SLX4 to DNA interstrand crosslinks (ICLs), yet how SLX4 is targeted to other functional contexts remains unclear. Here, we show that SLX4 binds SUMO-2/3 chains via SUMO-interacting motifs (SIMs). The SIMs of SLX4 are dispensable for ICL repair but important for processing CPT-induced replication intermediates, suppressing fragile site instability, and localizing SLX4 to ALT telomeres. The localization of SLX4 to laser-induced DNA damage also requires the SIMs, as well as DNA end resection, UBC9, and MDC1. Furthermore, the SUMO binding of SLX4 enhances its interaction with specific DNA-damage sensors or telomere-binding proteins, including RPA, MRE11-RAD50-NBS1, and TRF2. Thus, the interactions of SLX4 with SUMO and ubiquitin increase its affinity for factors recognizing different DNA lesions or telomeres, helping to direct the SLX4 complex in distinct functional contexts. C1 [Ouyang, Jian; Hallet, Alexander; Hai Dang Nguyen; Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Garner, Elizabeth; Rickman, Kimberly A.; Smogorzewska, Agata] Rockefeller Univ, Lab Genome Maintenance, New York, NY 10065 USA. [Gill, Grace] Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. RP Smogorzewska, A (reprint author), Rockefeller Univ, Lab Genome Maintenance, New York, NY 10065 USA. EM agata.smogorzewska@mail.rockefeller.edu; zou.lee@mgh.harvard.edu FU Doris Duke Clinical Scientist Development Award; Rockefeller University; NIH Training Program grant [T32GM007739]; NIH [GM076388, R01HL120922]; Federal Share of MGH Proton Program; Burroughs Wellcome Fund Career Award for Medical Scientists; Doris Duke Charitable Foundation FX We thank Drs. R. Baer, R. Hay, T. Hunter, and J. Jin for reagents, and members of the Zou lab for helpful discussions. L.Z. is a Jim & Ann Orr Massachusetts General Hospital Research Scholar. A.S. is a Rita Allen Foundation scholar, an Irma T. Hirschl scholar, an Alexandrine and Alexander Sinsheimer Foundation scholar, and a recipient of a Doris Duke Clinical Scientist Development Award. E.G. is a recipient of the Women & Science fellowship from The Rockefeller University. K.A.R. was supported by the NIH Training Program grant T32GM007739 to the Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program. This work was supported by grants from NIH (GM076388 to L.Z. and R01HL120922 to A.S.), the Federal Share of MGH Proton Program (L.Z.), the Burroughs Wellcome Fund Career Award for Medical Scientists (A.S.), and the Doris Duke Charitable Foundation (A.S.). NR 71 TC 27 Z9 27 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD JAN 8 PY 2015 VL 57 IS 1 BP 108 EP 122 DI 10.1016/j.molcel.2014.11.015 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AY6ZM UT WOS:000347711100010 PM 25533185 ER PT J AU Shen, RR Zhou, AY Kim, E O'Connell, JT Hagerstrand, D Beroukhim, R Hahn, WC AF Shen, R. R. Zhou, A. Y. Kim, E. O'Connell, J. T. Hagerstrand, D. Beroukhim, R. Hahn, W. C. TI TRAF2 is an NF-kappa B-activating oncogene in epithelial cancers SO ONCOGENE LA English DT Article DE TRAF2; NF-kappa B; cancer; 9q34 amplification ID TUMOR-SUPPRESSOR CYLD; K63-LINKED POLYUBIQUITINATION; MULTIPLE-MYELOMA; CELL LYMPHOMA; MOUSE MODEL; IKK; PHOSPHORYLATION; TUMORIGENESIS; MUTATIONS; PATHWAY AB Aberrant nuclear factor (NF)-kappa B activation is frequently observed in human cancers. Genome characterization efforts have identified genetic alterations in multiple components of the NF-kappa B pathway, some of which have been shown to be essential for cancer initiation and tumor maintenance. Here, using patient tumors and cancer cell lines, we identify the NF-kappa B regulator, TRAF2 (tumor necrosis factor (TNF) receptor-associated factor 2), as an oncogene that is recurrently amplified and rearranged in 15% of human epithelial cancers. Suppression of TRAF2 in cancer cells harboring TRAF2 copy number gain inhibits proliferation, NF-kappa B activation, anchorage-independent growth and tumorigenesis. Cancer cells that are dependent on TRAF2 also require NF-kappa B for survival. The phosphorylation of TRAF2 at serine 11 is essential for the survival of cancer cells harboring TRAF2 amplification. Together, these observations identify TRAF2 as a frequently amplified oncogene. C1 [Shen, R. R.; Zhou, A. Y.; Kim, E.; O'Connell, J. T.; Hagerstrand, D.; Beroukhim, R.; Hahn, W. C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Shen, R. R.; Zhou, A. Y.; Kim, E.; O'Connell, J. T.; Hagerstrand, D.; Beroukhim, R.; Hahn, W. C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Shen, R. R.; Zhou, A. Y.; Kim, E.; O'Connell, J. T.; Hagerstrand, D.; Beroukhim, R.; Hahn, W. C.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1538, Boston, MA 02215 USA. EM William_Hahn@dfci.harvard.edu RI Hagerstrand, Daniel/D-1584-2014 OI Hagerstrand, Daniel/0000-0001-7270-0776 FU Ruth L. Kirschstein National Research Service Award [F32 CA128265]; Aid for Cancer Research; [R01 CA130988] FX We thank members of the Hahn lab and the Cichowski lab for thoughtful discussion, reagents and technical assistance. We also thank Hasem Habelhah for providing the pTRAF2 (Ser11) antibody. We further thank Shumei Wang, Anita Hawkins, Chengzeng Zhang and Cynthia Morton at the DFCI Cytogenetics Core for TRAF2 FISH analysis and discussion. This work was supported in part by R01 CA130988 (to WCH), a Ruth L. Kirschstein National Research Service Award F32 CA128265 (to RRS) and The Aid for Cancer Research (to RRS). NR 43 TC 7 Z9 8 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JAN 8 PY 2015 VL 34 IS 2 BP 209 EP 216 DI 10.1038/onc.2013.543 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AY8FS UT WOS:000347790500008 PM 24362534 ER PT J AU Tolaney, SM Barry, WT Dang, CT Yardley, DA Moy, B Marcom, PK Albain, KS Rugo, HS Ellis, M Shapira, I Wolff, AC Carey, LA Overmoyer, BA Partridge, AH Guo, H Hudis, CA Krop, IE Burstein, HJ Winer, EP AF Tolaney, Sara M. Barry, William T. Dang, Chau T. Yardley, Denise A. Moy, Beverly Marcom, P. Kelly Albain, Kathy S. Rugo, Hope S. Ellis, Matthew Shapira, Iuliana Wolff, Antonio C. Carey, Lisa A. Overmoyer, Beth A. Partridge, Ann H. Guo, Hao Hudis, Clifford A. Krop, Ian E. Burstein, Harold J. Winer, Eric P. TI Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID METASTATIC BREAST; MONOCLONAL-ANTIBODY; CHEMOTHERAPY; EFFICACY; WOMEN; OVEREXPRESSION; ONCOGENE; DISEASE; TRIALS; SAFETY AB BACKGROUND No single standard treatment exists for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)-positive breast cancers, because most of these patients have been ineligible for the pivotal trials of adjuvant trastuzumab. METHODS We performed an uncontrolled, single-group, multicenter, investigator-initiated study of adjuvant paclitaxel and trastuzumab in 406 patients with tumors measuring up to 3 cm in greatest dimension. Patients received weekly treatment with paclitaxel and trastuzumab for 12 weeks, followed by 9 months of trastuzumab monotherapy. The primary end point was survival free from invasive disease. RESULTS The median follow-up period was 4.0 years. The 3-year rate of survival free from invasive disease was 98.7% (95% confidence interval [CI], 97.6 to 99.8). Among the 12 relapses seen, 2 were due to distant metastatic breast cancer. Excluding contralateral HER2-negative breast cancers and nonbreast cancers, 7 disease-specific events were noted. A total of 13 patients (3.2%; 95% CI, 1.7 to 5.4) reported at least one episode of grade 3 neuropathy, and 2 had symptomatic congestive heart failure (0.5%; 95% CI, 0.1 to 1.8), both of whom had normalization of the left ventricular ejection fraction after discontinuation of trastuzumab. A total of 13 patients had significant asymptomatic declines in ejection fraction (3.2%; 95% CI, 1.7 to 5.4), as defined by the study, but 11 of these patients were able to resume trastuzumab therapy after a brief interruption. CONCLUSIONS Among women with predominantly stage I HER2-positive breast cancer, treatment with adjuvant paclitaxel plus trastuzumab was associated with a risk of early recurrence of about 2%; 6% of patients withdrew from the study because of protocol-specified adverse events. (Funded by Genentech; ClinicalTrials.gov number, NCT00542451.) C1 [Tolaney, Sara M.; Overmoyer, Beth A.; Partridge, Ann H.; Krop, Ian E.; Burstein, Harold J.; Winer, Eric P.] Massachusetts Gen Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02114 USA. [Barry, William T.; Guo, Hao] Massachusetts Gen Hosp, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02114 USA. [Moy, Beverly] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Dang, Chau T.; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, Solid Tumor Div, Dept Med, Breast Canc Med Serv, New York, NY 10021 USA. [Dang, Chau T.; Hudis, Clifford A.] Weill Cornell Med Ctr, Dept Med, New York, NY USA. [Shapira, Iuliana] Hofstra North Shore LIJ Sch Med, Dept Med Oncol, New Hyde Pk, NY USA. [Yardley, Denise A.] Sarah Cannon Canc Ctr, Dept Med Oncol, Nashville, TN USA. [Marcom, P. Kelly] Duke Canc Inst, Dept Med, Div Med Oncol, Durham, NC USA. [Carey, Lisa A.] Univ N Carolina, Dept Med Oncol, Chapel Hill, NC USA. [Albain, Kathy S.] Loyola Univ Chicago Stritch Sch Med, Div Hematol Oncol, Dept Med, Cardinal Bernardin Canc Ctr, Maywood, IL USA. [Rugo, Hope S.] Univ Calif San Francisco, Div Oncol, Dept Med, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Ellis, Matthew] Washington Univ, Dept Med Oncol, St Louis, MO 63130 USA. [Wolff, Antonio C.] Johns Hopkins Kimmel Canc Ctr, Dept Oncol, Baltimore, MD USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM ewiner@-partners.org RI Guo, Hao/E-8921-2015; OI Guo, Hao/0000-0003-1658-0989; Wolff, Antonio/0000-0003-3734-1063 FU Genentech FX Funded by Genentech; ClinicalTrials.gov number, NCT00542451. NR 19 TC 101 Z9 109 U1 1 U2 27 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 8 PY 2015 VL 372 IS 2 BP 134 EP 141 DI 10.1056/NEJMoa1406281 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AY2UA UT WOS:000347443300008 PM 25564897 ER PT J AU Moy, B Specht, MC Lanuti, M Rafferty, EA Lerwill, MF AF Moy, Beverly Specht, Michelle C. Lanuti, Michael Rafferty, Elizabeth A. Lerwill, Melinda F. TI Case 1-2015: A 66-Year-Old Woman with Metastatic Breast Cancer after Endocrine Therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ESTROGEN-RECEPTOR; POSTMENOPAUSAL WOMEN; ADJUVANT TAMOXIFEN; COMBINATION TRIAL; RANDOMIZED-TRIAL; MRI; LETROZOLE; TUMORS; RECURRENCE; MUTATIONS C1 [Moy, Beverly] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Specht, Michelle C.; Lanuti, Michael] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rafferty, Elizabeth A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lerwill, Melinda F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Moy, Beverly] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Specht, Michelle C.; Lanuti, Michael] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Rafferty, Elizabeth A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Lerwill, Melinda F.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Moy, B (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 32 TC 1 Z9 1 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 8 PY 2015 VL 372 IS 2 BP 162 EP 170 DI 10.1056/NEJMcpc1408601 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AY2UA UT WOS:000347443300012 PM 25564900 ER PT J AU Lorenzon, P Redolfi, N Podolsky, MJ Zamparo, I Franchi, SA Pietra, G Boccaccio, A Menini, A Murthy, VN Lodovichi, C AF Lorenzon, Paolo Redolfi, Nelly Podolsky, Michael J. Zamparo, Ilaria Franchi, Sira Angela Pietra, Gianluca Boccaccio, Anna Menini, Anna Murthy, Venkatesh N. Lodovichi, Claudia TI Circuit Formation and Function in the Olfactory Bulb of Mice with Reduced Spontaneous Afferent Activity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE behavior; functional imaging; olfactory bulb; olfactory system; sensory map; topography ID GENE-TARGETED MICE; SENSORY NEURONS; ODORANT RECEPTORS; ELECTRICAL-ACTIVITY; CRITICAL PERIOD; IN-VIVO; TOPOGRAPHIC ORGANIZATION; TRANSGENIC MICE; EVOKED ACTIVITY; MAP AB The type of neuronal activity required for circuit development is a matter of significant debate. We addressed this issue by analyzing the topographic organization of the olfactory bulb in transgenic mice engineered to have very little afferent spontaneous activity due to the overexpression of the inwardly rectifying potassium channel Kir2.1 in the olfactory sensory neurons (Kir2.1 mice). In these conditions, the topography of the olfactory bulb was unrefined. Odor-evoked responses were readily recorded in glomeruli with reduced spontaneous afferent activity, although the functional maps were coarser than in controls and contributed to altered olfactory discrimination behavior. In addition, overexpression of Kir2.1 in adults induced a regression of the already refined connectivity to an immature (i. e., coarser) status. Our data suggest that spontaneous activity plays a critical role not only in the development but also in the maintenance of the topography of the olfactory bulb and in sensory information processing. C1 [Lorenzon, Paolo; Redolfi, Nelly; Zamparo, Ilaria; Franchi, Sira Angela; Lodovichi, Claudia] Venetian Inst Mol Med, I-35129 Padua, Italy. [Podolsky, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pietra, Gianluca; Menini, Anna] Scuola Int Super Studi Avanzati, SISSA, Neurobiol Grp, I-34136 Trieste, Italy. [Boccaccio, Anna] CNR, Inst Biophys, I-16149 Genoa, Italy. [Murthy, Venkatesh N.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Murthy, Venkatesh N.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Lodovichi, Claudia] CNR, Inst Neurosci, Padua, Italy. RP Lodovichi, C (reprint author), CNR, Inst Neurosci, Via Orus 2-35129, Padua, Italy. EM claudia.lodovichi@unipd.it RI Boccaccio, Anna/H-6816-2012; OI Boccaccio, Anna/0000-0002-6219-2285; Menini, Anna/0000-0001-9304-0412 FU Armenise-Harvard Career Developmental Award; Cariparo Grant FX This work was supported by an Armenise-Harvard Career Developmental Award and by the Cariparo Grant to C.L. We are grateful to J.A. Gogos for generously providing the P2-IRES-GFP and the teto-Kir2.1-IRES-tauLacZ mice. We thank Luca Dall'Arche for helping with behavioral experiments. NR 68 TC 3 Z9 3 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 7 PY 2015 VL 35 IS 1 BP 146 EP 160 DI 10.1523/JNEUROSCI.0613-14.2015 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CB1SB UT WOS:000349407200013 PM 25568110 ER PT J AU Sadleir, KR Eimer, WA Cole, SL Vassar, R AF Sadleir, Katherine R. Eimer, William A. Cole, Sarah L. Vassar, Robert TI A beta reduction in BACE1 heterozygous null 5XFAD mice is associated with transgenic APP level SO Molecular Neurodegeneration LA English DT Article DE beta-secretase; Amyloid precursor protein; Alzheimer's disease; APP transgenic mouse models; 5XFAD; BACE1 heterozygous; Amyloid; A beta; Dot blot; Estrogen response element ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; SECRETASE BACE1; MEMORY DEFICITS; KNOCKOUT MICE; AXON GUIDANCE; NEURON LOSS; ENZYME 1; IN-VIVO; EXPRESSION AB Background: The beta-secretase, BACE1, cleaves APP to initiate generation of the beta-amyloid peptide, A beta, that comprises amyloid plaques in Alzheimer's disease (AD). Reducing BACE1 activity is an attractive therapeutic approach to AD, but complete inhibition of BACE1 could have mechanism-based side-effects as BACE1(-/-) mice show deficits in axon guidance, myelination, memory, and other neurological processes. Since BACE1(+/-) mice appear normal there is interest in determining whether 50% reduction in BACE1 is potentially effective in preventing or treating AD. APP transgenic mice heterozygous for BACE1 have decreased A beta but the extent of reduction varies greatly from study to study. Here we assess the effects of 50% BACE1 reduction on the widely used 5XFAD mouse model of AD. Results: 50% BACE1 reduction reduces A beta 42, plaques, and BACE1-cleaved APP fragments in female, but not in male, 5XFAD/ BACE1(+/-) mice. 5XFAD/ BACE1(+/+) females have higher levels of A beta 42 and steady-state transgenic APP than males, likely caused by an estrogen response element in the transgene Thy-1 promoter. We hypothesize that higher transgenic APP level in female 5XFAD mice causes BACE1 to no longer be in excess over APP so that 50% BACE1 reduction has a significant A beta 42 lowering effect. In contrast, the lower APP level in 5XFAD males allows BACE1 to be in excess over APP even at 50% BACE1 reduction, preventing lowering of A beta 42 in 5XFAD/ BACE1(+/-) males. We also developed and validated a dot blot assay with an A beta 42-selective antibody as an accurate and cost-effective alternative to ELISA for measuring cerebral A beta 42 levels. Conclusions: 50% BACE1 reduction lowers A beta 42 in female 5XFAD mice only, potentially because BACE1 is not in excess over APP in 5XFAD females with higher transgene expression, while BACE1 is in excess over APP in 5XFAD males with lower transgene expression. Our results suggest that greater than 50% BACE1 inhibition might be necessary to significantly lower A beta, given that BACE1 is likely to be in excess over APP in the human brain. Additionally, in experiments using the 5XFAD mouse model, or other Thy-1 promoter transgenic mice, equal numbers of male and female mice should be used, in order to avoid artifactual gender-related differences. C1 [Sadleir, Katherine R.; Eimer, William A.; Cole, Sarah L.; Vassar, Robert] Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60605 USA. [Eimer, William A.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Cole, Sarah L.] Takeda Cambridge, Neurodegenerat Grp, Cambridge, England. RP Vassar, R (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60605 USA. EM r-vassar@northwestern.edu FU National Insititutes of Health [R01 AG022560, R01 AG030142]; NIH [F32AG033445, 5T32AG00026]; Northwestern University Cell Imaging Facility; Cancer Center [NCI CA060553] FX This work was supported by the National Insititutes of Health R01 AG022560 and R01 AG030142 to Dr. Robert Vassar, NIH F32AG033445 and 5T32AG00026 to Dr. Katherine R. Sadleir, and the Northwestern University Cell Imaging Facility and a Cancer Center Support Grant (NCI CA060553). NR 42 TC 8 Z9 8 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD JAN 7 PY 2015 VL 10 AR 1 DI 10.1186/1750-1326-10-1 PG 16 WC Neurosciences SC Neurosciences & Neurology GA CA7WH UT WOS:000349127600001 PM 25567526 ER PT J AU Wood, KB Buttermann, GR Phukan, R Harrod, CC Mehbod, A Shannon, B Bono, CM Harris, MB AF Wood, Kirkham B. Buttermann, Glenn R. Phukan, Rishabh Harrod, Christopher C. Mehbod, Amir Shannon, Brian Bono, Christopher M. Harris, Mitchel B. TI Operative Compared with Nonoperative Treatment of a Thoracolumbar Burst Fracture without Neurological Deficit SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID NONSURGICAL TREATMENT; SPINAL-INJURIES; LUMBAR SPINE; MANAGEMENT; REDUCTION; FUSION; INSTRUMENTATION; JUNCTION AB Background: Studies comparing operative with nonoperative treatment of a stable burst fracture of the thoracolumbar junction in neurologically intact patients have not shown a meaningful difference at early follow-up. To our knowledge, longer-term outcome data have not before been presented. Methods: From 1992 to 1998, forty-seven consecutive patients with a stable thoracolumbar burst fracture and no neurological deficit were evaluated and randomized to one of two treatment groups: operative treatment (posterior or anterior arthrodesis) or nonoperative treatment (a body cast or orthosis). We previously reported the results of follow-up at an average of forty-four months. The current study presents the results of long-term follow-up, at an average of eighteen years (range, sixteen to twenty-two years). As in the earlier study, patients at long-term follow-up indicated the degree of pain on a visual analog scale and completed the Roland and Morris disability questionnaire, the Oswestry Disability Index (ODI) questionnaire, and the Short Form-36 (SF-36) health survey. Work and health status were obtained, and patients were evaluated radiographically. Results: Of the original operatively treated group of twenty-four patients, follow-up data were obtained for nineteen; one patient had died, and four could not be located. Of the original nonoperatively treated group of twenty-three patients, data were obtained for eighteen; two patients had died, and three could not be located. The average kyphosis was not significantly different between the two groups (13 degrees for those who received operative treatment compared with 19 degrees for those treated nonoperatively). Median scores for pain (4 cm for the operative group and 1.5 cm for the nonoperative group; p = 0.003), ODI scores (20 for the operative group and 2 for the nonoperative group; p < 0.001) and Roland and Morris scores (7 for the operative group and 1 for the nonoperative group; p = 0.001) were all significantly better in the group treated nonoperatively. Seven of eight SF-36 scores also favored nonoperative treatment. Conclusions: While early analysis (four years) revealed few significant differences between the two groups, at long-term follow-up (sixteen to twenty-two years), those with a stable burst fracture who were treated nonoperatively reported less pain and better function compared with those who were treated surgically. C1 Univ Minnesota, Dept Orthopaed Surg, Minneapolis, MN 55455 USA. [Mehbod, Amir] Twin Cities Spine Ctr, Minneapolis, MN USA. Ramsey Med Ctr, St Paul, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Wood, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, 55 Fruit St,Yawkey OCC 3800, Boston, MA 02114 USA. EM kbwood@partners.org NR 32 TC 11 Z9 14 U1 0 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JAN 7 PY 2015 VL 97A IS 1 BP 3 EP 9 DI 10.2106/JBJS.N.00226 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AY3IJ UT WOS:000347477300008 PM 25568388 ER PT J AU Guo, YM Wang, Z Mayer, EA Holschneider, DP AF Guo, Yumei Wang, Zhuo Mayer, Emeran A. Holschneider, Daniel P. TI Neonatal stress from limited bedding elicits visceral hyperalgesia in adult rats SO NEUROREPORT LA English DT Article DE abdominal pain; colorectal distension; early life stress; irritable bowel syndrome; nesting behavior; nociception; sex differences; visceral pain ID EARLY-LIFE STRESS; IRRITABLE-BOWEL-SYNDROME; MATERNAL SEPARATION; ESTROUS-CYCLE; COLONIC DISTENSION; SEX-DIFFERENCES; MODEL; VISCEROMOTOR; RESPONSES; ABUSE AB Early life stress is a risk factor for developing functional pain disorders. The 'limited bedding' (LB) model elicits psychological stress in the dam and her pups by providing minimal nesting material following delivery. Little is known about the effects of LB on visceral pain. Rats (female, male) were exposed to LB on postnatal days 2-9. Electromyographic visceromotor responses were recorded at the age of 11-12 weeks during titrated colorectal distension. LB exposure resulted in significant visceral hyperalgesia in both sexes. Sex differences were demonstrated only in nonstressed controls, with females showing a greater visceromotor response. Our results prepare the way for use of the LB model in studying the development of visceral pain in adults with functional gastrointestinal disorders. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Guo, Yumei; Wang, Zhuo; Holschneider, Daniel P.] Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 90089 USA. [Holschneider, Daniel P.] Univ So Calif, Dept Neurol Cell & Neurobiol, Los Angeles, CA 90089 USA. [Wang, Zhuo; Mayer, Emeran A.; Holschneider, Daniel P.] Univ Calif Los Angeles, Dept Med, Ctr Neurobiol Stress, Los Angeles, CA 90024 USA. [Mayer, Emeran A.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. [Mayer, Emeran A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Mayer, Emeran A.] Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA USA. [Mayer, Emeran A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Holschneider, DP (reprint author), Univ So Calif, Dept Psychiat & Behav Sci, 1975 Zonal Ave,KAM 400,MC 9037, Los Angeles, CA 90089 USA. EM holschne@usc.edu FU United States National Institutes of Health [P50DK064539] FX The research was supported by United States National Institutes of Health grants P50DK064539 (Mayer). NR 25 TC 8 Z9 8 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 EI 1473-558X J9 NEUROREPORT JI Neuroreport PD JAN 7 PY 2015 VL 26 IS 1 BP 13 EP 16 DI 10.1097/WNR.0000000000000292 PG 4 WC Neurosciences SC Neurosciences & Neurology GA AU7OW UT WOS:000345790900003 PM 25426824 ER PT J AU Cypess, AM Weiner, LS Roberts-Toler, C Elia, EF Kessler, SH Kahn, PA English, J Chatman, K Trauger, SA Doria, A Kolodny, GM AF Cypess, Aaron M. Weiner, Lauren S. Roberts-Toler, Carla Elia, Elisa Franquet Kessler, Skyler H. Kahn, Peter A. English, Jeffrey Chatman, Kelly Trauger, Sunia A. Doria, Alessandro Kolodny, Gerald M. TI Activation of Human Brown Adipose Tissue by a beta 3-Adrenergic Receptor Agonist SO CELL METABOLISM LA English DT Article ID SELECTIVE BETA(3)-ADRENOCEPTOR AGONIST; ADULT HUMANS; ADRENOCEPTOR AGONIST; ENERGY-EXPENDITURE; COLD-EXPOSURE; DOUBLE-BLIND; FAT; THERMOGENESIS; METABOLISM; MIRABEGRON AB Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of beta 3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity has never been demonstrated in humans. Here we determined the ability of 200 mg oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a beta 3-AR agonist currently approved to treat overactive bladder, to stimulate BAT as compared to placebo. Mirabegron led to higher BAT metabolic activity as measured via F-18-fluorodeoxyglucose (F-18-FDG) using positron emission tomography (PET) combined with computed tomography (CT) in all twelve healthy male subjects (p = 0.001), and it increased resting metabolic rate (RMR) by 203 +/- 40 kcal/day (+ 13%; p = 0.001). BAT metabolic activity was also a significant predictor of the changes in RMR (p = 0.006). Therefore, a beta 3-AR agonist can stimulate human BAT thermogenesis and may be a promising treatment for metabolic disease. C1 [Cypess, Aaron M.; Weiner, Lauren S.; Roberts-Toler, Carla; Kessler, Skyler H.] Harvard Univ, Sch Med, Sect Integrat Physiol & Metab, Res Div,Joslin Diabet Ctr, Boston, MA 02215 USA. [Elia, Elisa Franquet; English, Jeffrey; Kolodny, Gerald M.] Harvard Univ, Sch Med, Div Nucl Med & Mol Imaging, Dept Radiol,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kahn, Peter A.] Albert Einstein Coll Med, Bronx, NY 10461 USA. [Chatman, Kelly; Trauger, Sunia A.] Harvard Univ, Small Mol Mass Spectrometry Facil, FAS Div Sci, Cambridge, MA 02138 USA. [Doria, Alessandro] Harvard Univ, Sch Med, Sect Genet & Epidemiol, Res Div,Joslin Diabet Ctr, Boston, MA 02215 USA. RP Cypess, AM (reprint author), Harvard Univ, Sch Med, Sect Integrat Physiol & Metab, Res Div,Joslin Diabet Ctr, Boston, MA 02215 USA. EM Aaron.Cypess@joslin.harvard.edu FU National Institutes of Health (NIH) [K23 DK081604, P30 DK036836]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Fundacion Alfonso Martin Escudero; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources [UL1 RR025758]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Science) [UL1TR000170, UL1TR001102]; Harvard University; Chugai Pharmaceutical Co., Ltd through Joslin Diabetes Center; Molecular Metabolism, LLC through Joslin Diabetes Center; Sanofi FX This work was supported by National Institutes of Health (NIH) grants K23 DK081604 and P30 DK036836 (including a P&F award) and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); the Fundacion Alfonso Martin Escudero; Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources award UL1 RR025758 and National Center for Advancing Translational Science awards UL1TR000170 and UL1TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the NIH.; Dr. Cypess is a recipient of sponsored research grants from Chugai Pharmaceutical Co., Ltd, and Molecular Metabolism, LLC, both through Joslin Diabetes Center; and he has received payment for lecturing about clinical diabetes on behalf of Joslin Diabetes Center to employees of Sanofi, Genentech, Eli Lilly, Janssen, and Regeneron. Dr. Doria has received research support from Sanofi. NR 37 TC 125 Z9 127 U1 5 U2 45 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD JAN 6 PY 2015 VL 21 IS 1 BP 33 EP 38 DI 10.1016/j.cmet.2014.12.009 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AY3ER UT WOS:000347467900008 PM 25565203 ER PT J AU Palsson-McDermott, EM Curtis, AM Goel, G Lauterbach, MAR Sheedy, FJ Gleeson, LE van den Bosch, MWM Quinn, SR Domingo-Fernandez, R Johnson, DGW Jiang, JK Israelsen, WJ Keane, J Thomas, C Clish, C Vanden Heiden, M Xavier, RJ O'Neill, LAJ AF Palsson-McDermott, Eva M. Curtis, Anne M. Goel, Gautam Lauterbach, Mario A. R. Sheedy, Frederick J. Gleeson, Laura E. van den Bosch, Mirjam W. M. Quinn, Susan R. Domingo-Fernandez, Raquel Johnson, Daniel G. W. Jiang, Jain-kang Israelsen, William J. Keane, Joseph Thomas, Craig Clish, Clary Vanden Heiden, Matthew Xavier, Ramnik J. O'Neill, Luke A. J. TI Pyruvate Kinase M2 Regulates Hif-1 alpha Activity and IL-1 beta Induction and Is a Critical Determinant of the Warburg Effect in LPS-Activated Macrophages SO CELL METABOLISM LA English DT Article ID TUMOR-GROWTH; MYCOBACTERIUM-TUBERCULOSIS; NUCLEAR TRANSLOCATION; CANCER METABOLISM; PKM2; ISOFORM; PROMOTES; GLUCOSE; GENE; FRUCTOSE-1,6-BISPHOSPHATE AB Macrophages activated by the TLR4 agonist LPS undergo dramatic changes in their metabolic activity. We here show that LPS induces expression of the key metabolic regulator Pyruvate Kinase M2 (PKM2). Activation of PKM2 using two well-characterized small molecules, DASA-58 and TEPP-46, inhibited LPS-induced Hif-1 alpha and IL-1 beta, as well as the expression of a range of other Hif-1 alpha-dependent genes. Activation of PKM2 attenuated an LPS-induced proinflammatory M1 macrophage phenotype while promoting traits typical of an M2 macrophage. We show that LPS-induced PKM2 enters into a complex with Hif-1 alpha, which can directly bind to the IL-1b promoter, an event that is inhibited by activation of PKM2. Both compounds inhibited LPS-induced glycolytic reprogramming and succinate production. Finally, activation of PKM2 by TEPP-46 in vivo inhibited LPS and Salmonella typhimurium-induced IL-1 beta production, while boosting production of IL-10. PKM2 is therefore a critical determinant of macrophage activation by LPS, promoting the inflammatory response. C1 [Palsson-McDermott, Eva M.; Curtis, Anne M.; Lauterbach, Mario A. R.; van den Bosch, Mirjam W. M.; Quinn, Susan R.; Domingo-Fernandez, Raquel; Johnson, Daniel G. W.; O'Neill, Luke A. J.] Univ Dublin Trinity Coll, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin 2, Ireland. [Goel, Gautam; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Goel, Gautam; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Goel, Gautam; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Goel, Gautam; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Goel, Gautam; Clish, Clary; Xavier, Ramnik J.] Broad Inst Harvard Univ & Massachusetts Inst Tec, Cambridge, MA 02142 USA. [Sheedy, Frederick J.; Gleeson, Laura E.; Keane, Joseph] Univ Dublin Trinity Coll, Dept Clin Med, Sch Med, Dublin 2, Ireland. [Israelsen, William J.; Vanden Heiden, Matthew] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA. [Jiang, Jain-kang; Thomas, Craig] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Vanden Heiden, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP O'Neill, LAJ (reprint author), Univ Dublin Trinity Coll, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin 2, Ireland. EM laoneill@tcd.ie OI Keane, Joseph/0000-0001-5313-385X FU Science Foundation Ireland; European Research Council; Health Research Board; European Community [HEALTH-14-2011-281608]; Wellcome Trust; Baggot St Hospital Trust; National Institutes of Health FX We thank Science Foundation Ireland, the European Research Council, the Health Research Board, European Community Seventh Framework Programme (FP7-2007-2013) under grant agreement No. HEALTH-14-2011-281608 'TIMER', Wellcome Trust, Baggot St Hospital Trust, and National Institutes of Health for funding. NR 36 TC 70 Z9 71 U1 11 U2 39 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD JAN 6 PY 2015 VL 21 IS 1 BP 65 EP 80 DI 10.1016/j.cmet.2014.12.005 PG 16 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AY3ER UT WOS:000347467900011 PM 25565206 ER PT J AU Burns, SM Vetere, A Walpita, D Dancik, V Khodier, C Perez, J Clemons, PA Wagner, BK Altshuler, D AF Burns, Sean M. Vetere, Amedeo Walpita, Deepika Dancik, Vlado Khodier, Carol Perez, Jose Clemons, Paul A. Wagner, Bridget K. Altshuler, David TI High-Throughput Luminescent Reporter of Insulin Secretion for Discovering Regulators of Pancreatic Beta-Cell Function SO CELL METABOLISM LA English DT Article ID SELECTIVE SEROTONIN; CA2+ CHANNELS; GLUCOSE; EXPRESSION; CULTURE; LINE; GLUCOKINASE; PROINSULIN; METABOLISM; LUCIFERASE AB Defects in insulin secretion play a central role in the pathogenesis of type 2 diabetes, yet the mechanisms driving beta-cell dysfunction remain poorly understood, and therapies to preserve glucose-dependent insulin release are inadequate. We report a luminescent insulin secretion assay that enables large-scale investigations of beta-cell function, created by inserting Gaussia luciferase into the C-peptide portion of proinsulin. Beta-cell lines expressing this construct cosecrete luciferase and insulin in close correlation, under both standard conditions or when stressed by cytokines, fatty acids, or ER toxins. We adapted the reporter for high-throughput assays and performed a 1,600-compound pilot screen, which identified several classes of drugs inhibiting secretion, as well as glucose-potentiated secretagogues that were confirmed to have activity in primary human islets. Requiring 40-fold less time and expense than the traditional ELISA, this assay may accelerate the identification of pathways governing insulin secretion and compounds that safely augment beta-cell function in diabetes. C1 [Burns, Sean M.; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Burns, Sean M.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Burns, Sean M.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Altshuler, David] MIT, Dept Biol, Cambridge, MA 02142 USA. [Burns, Sean M.; Altshuler, David] Broad Inst Harvard & MIT, Med & Populat Genet Program, Cambridge, MA 02142 USA. [Vetere, Amedeo; Walpita, Deepika; Dancik, Vlado; Clemons, Paul A.; Wagner, Bridget K.] Broad Inst Harvard & MIT, Ctr Sci Therapeut, Cambridge, MA 02142 USA. [Khodier, Carol; Perez, Jose] Broad Inst Harvard & MIT, Ctr Dev Therapeut, Cambridge, MA 02142 USA. RP Burns, SM (reprint author), Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. EM sburns@broadinstitute.org OI Vetere, Amedeo/0000-0001-5608-0773 FU Carlos Slim Foundation in Mexico FX The work was conducted as part of the Slim Initiative for Genomic Medicine, a project funded by the Carlos Slim Foundation in Mexico. A patent has been filed for the insulin secretion reporter. We thank colleagues at the Massachusetts General Hospital, Broad Institute, and Joslin Diabetes Center for helpful conversations, in particular members of the D.A., Daly, and B.K.W. laboratories, as well as Joseph Avruch, Stuart Schreiber, Nicola Tolliday, Thomas Hasaka, Bakhos Tannous, Gordon Weir, and Susan Bonner-Weir. NR 38 TC 10 Z9 10 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD JAN 6 PY 2015 VL 21 IS 1 BP 126 EP 137 DI 10.1016/j.cmet.2014.12.010 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AY3ER UT WOS:000347467900016 PM 25565210 ER PT J AU Packer, M McMurray, JJV Desai, AS Gong, J Lefkowitz, MP Rizkala, AR Rouleau, JL Shi, VC Solomon, SD Swedberg, K Zile, M Andersen, K Arango, JL Arnold, JM Belohlavek, J Bohm, M Boytsov, S Burgess, LJ Cabrera, W Calvo, C Chen, CH Dukat, A Duarte, YC Erglis, A Fu, M Gomez, E Gonzalez-Medina, A Hagege, AA Huang, J Katova, T Kiatchoosakun, S Kim, KS Kozan, O Llamas, EB Martinez, F Merkely, B Mendoza, I Mosterd, A Negrusz-Kawecka, M Peuhkurinen, K Ramires, FJA Refsgaard, J Rosenthal, A Senni, M Jr, ASS Silva-Cardoso, J Squire, IB Starling, RC Teerlink, JR Vanhaecke, J Vinereanu, D Wong, RCC AF Packer, Milton McMurray, John J. V. Desai, Akshay S. Gong, Jianjian Lefkowitz, Martin P. Rizkala, Adel R. Rouleau, Jean L. Shi, Victor C. Solomon, Scott D. Swedberg, Karl Zile, Michael Andersen, Karl Arango, Juan Luis Arnold, J. Malcolm Belohlavek, Jan Boehm, Michael Boytsov, Sergey Burgess, Lesley J. Cabrera, Walter Calvo, Carlos Chen, Chen-Huan Dukat, Andrej Duarte, Yan Carlos Erglis, Andrejs Fu, Michael Gomez, Efrain Gonzalez-Medina, Angel Hagege, Albert A. Huang, Jun Katova, Tzvetana Kiatchoosakun, Songsak Kim, Kee-Sik Kozan, Oemer Llamas, Edmundo Bayram Martinez, Felipe Merkely, Bela Mendoza, Ivan Mosterd, Arend Negrusz-Kawecka, Marta Peuhkurinen, Keijo Ramires, Felix J. A. Refsgaard, Jens Rosenthal, Arvo Senni, Michele Jr, Antonio S. Sibulo Silva-Cardoso, Jose Squire, Iain B. Starling, Randall C. Teerlink, John R. Vanhaecke, Johan Vinereanu, Dragos Wong, Raymond Ching-Chiew CA PARADIGM-HF Investigators TI Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure SO CIRCULATION LA English DT Article DE heart failure; neprilysin; receptors, angiotensin ID LEFT-VENTRICULAR DYSFUNCTION; NATRIURETIC-PEPTIDE; NEUTRAL ENDOPEPTIDASE; CONVERTING ENZYME; MYOCARDIAL-INFARCTION; MILD SYMPTOMS; MORTALITY; TRIAL; ADRENOMEDULLIN; BRADYKININ AB Background-Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. Methods and Results-We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril. Conclusions-Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. C1 [Packer, Milton] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [McMurray, John J. V.] Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Desai, Akshay S.; Solomon, Scott D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gong, Jianjian; Lefkowitz, Martin P.; Rizkala, Adel R.; Shi, Victor C.] Novartis Pharmaceut, E Hanover, NJ USA. [Rouleau, Jean L.] Univ Montreal, Inst Cardiol, Montreal, PQ, Canada. [Swedberg, Karl] Dept Mol & Clin Med, Gothenburg, Sweden. [Zile, Michael] Med Univ S Carolina, Charleston, SC 29425 USA. [Zile, Michael] Vet Adm Med Ctr, RHJ Dept, Charleston, SC 29403 USA. [Andersen, Karl] Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland. [Arango, Juan Luis] Unidad Cirugia Cardiovasc Guatemala, Guatemala City, Guatemala. [Arnold, J. Malcolm] Univ Western Ontario, Dept Physiol & Med, London, ON N6A 3K7, Canada. [Belohlavek, Jan] Charles Univ Prague, Gen Univ Hosp, Dept Med 2, Prague, Czech Republic. [Belohlavek, Jan] Charles Univ Prague, Sch Med 1, Dept Med 2, Prague, Czech Republic. [Boehm, Michael] Univ Saarland, Dept Cardiol, Homburg, Germany. [Boytsov, Sergey] Natl Res Ctr Prevent Med, Moscow, Russia. [Burgess, Lesley J.] Univ Stellenbosch, Dept Internal Med, Cardiol Unit, TREAD Res, Parow, South Africa. [Burgess, Lesley J.] Tygerberg Hosp, Parow, South Africa. [Cabrera, Walter] Clin Vesalio, Lima, Peru. [Calvo, Carlos] Hosp Clin Univ, Unidad Hipertens Arterial & Riesgo Vasc, La Coruna, Spain. [Chen, Chen-Huan] Natl Yang Ming Univ, Dept Med, Taipei, Taiwan. [Dukat, Andrej] Comenius Univ, Dept Internal Med 2, Bratislava, Slovakia. [Duarte, Yan Carlos] Luis Vernaza Hosp, Guayaquil, Ecuador. [Erglis, Andrejs] Univ Latvia, Inst Cardiol, Fac Med, Riga, Latvia. [Fu, Michael] Ostra Hosp, Sahlgrenska Univ Hosp, Dept Med, S-41685 Gothenburg, Sweden. [Gomez, Efrain] Clin Shaio, Bogota, Colombia. [Gonzalez-Medina, Angel] Univ Autonoma Santo Domingo, Hosp Santo Domingo, Santo Domingo, Dominican Rep. [Hagege, Albert A.] Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, Paris, France. [Hagege, Albert A.] Paris Descartes Univ, Sorbonne Paris Cite, Paris, France. [Hagege, Albert A.] INSERM, U970, Paris Cardiovasc Res Ctr, Paris, France. [Huang, Jun] Nanjing Med Univ, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China. [Katova, Tzvetana] Natl Hosp Cardiol, Sofia, Bulgaria. [Kiatchoosakun, Songsak] Khon Kaen Univ, Khon Kaen, Thailand. [Kim, Kee-Sik] Daegu Catholic Univ Hosp, Taegu, South Korea. [Kozan, Oemer] Dokuz Eylul Univ, Fac Med, Izmir, Turkey. [Llamas, Edmundo Bayram] Fdn Cardiovasc Aguascalientes AC, Hidalgo, Mexico. [Martinez, Felipe] Univ Nacl Cordoba, Fdn Rusculleda, Inst DAMIC, RA-5000 Cordoba, Argentina. [Merkely, Bela] Semmelweis Univ, H-1085 Budapest, Hungary. [Mendoza, Ivan] Cent Univ Venezuela, Venezuela Inst Trop Med, Caracas, Venezuela. [Mosterd, Arend] Meander Med Ctr, Dept Cardiol, Amersfoort, Netherlands. [Mosterd, Arend] WCN Dutch Network Cardiovasc Res, Utrecht, Netherlands. [Negrusz-Kawecka, Marta] Wroclaw Med Univ, Dept & Clin Cardiol, Wroclaw, Poland. [Peuhkurinen, Keijo] Kuopio Univ Hosp, Dept Med, SF-70210 Kuopio, Finland. [Ramires, Felix J. A.] Univ Sao Paulo, Sch Med, Heart Inst InCor, BR-05508 Sao Paulo, Brazil. [Refsgaard, Jens] Viborg Hosp, Dept Cardiol, Viborg, Denmark. [Senni, Michele] Azienda Osped Papa Giovanni XXIII, Bergamo, Italy. [Jr, Antonio S. Sibulo] St Lukes Heart Inst, Quezon City, Philippines. [Silva-Cardoso, Jose] Univ Porto, Porto Med Sch, Ctr Hlth Technol & Serv Res CINTESIS, P-4100 Oporto, Portugal. [Squire, Iain B.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Squire, Iain B.] Glenfield Hosp, NIHR Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Starling, Randall C.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Vanhaecke, Johan] Univ Hosp KU Leuven, Dept Cardiovasc Dis, Leuven, Belgium. [Vinereanu, Dragos] Carol Davila Univ & Emergency Hosp, Univ Med & Pharm, Bucharest, Romania. [Wong, Raymond Ching-Chiew] Natl Univ Singapore, Ctr Heart, Dept Cardiol, Singapore 117548, Singapore. RP Packer, M (reprint author), Univ Texas SW Med Ctr Dallas, Dept Clin Sci, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM milton.packer@utsouthwestern.edu; john.mcmurray@glasgow.ac.uk RI Ramires, Felix/D-5996-2012; Libis, Roman/O-9193-2015; Rafalskiy, Vladimir/G-3172-2013; FMUP, CINTESIS/C-6631-2014; Zhilyaev, Evgeny/E-3774-2016; Urina, Miguel/H-2605-2016; Boytsov, Sergey/M-4486-2014; Drapkina, Oxana/G-8443-2016; OI Ramires, Felix/0000-0003-2437-2485; Libis, Roman/0000-0003-0130-990X; Rafalskiy, Vladimir/0000-0002-2503-9580; FMUP, CINTESIS/0000-0001-7248-2086; Zhilyaev, Evgeny/0000-0002-9443-1164; Urina, Miguel/0000-0001-6003-4622; Boytsov, Sergey/0000-0001-6998-8406; Drapkina, Oxana/0000-0002-4453-8430; Nightingale, Angus/0000-0001-9435-726X; Mohindra, Raj/0000-0002-8437-5066; Martinez-Selles, Manuel/0000-0003-0289-6229; Danzi, Gian Battista/0000-0003-0897-8006; mcmurray, john/0000-0002-6317-3975 FU Novartis FX The study was funded by Novartis. NR 42 TC 86 Z9 92 U1 4 U2 53 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 6 PY 2015 VL 131 IS 1 BP 54 EP 61 DI 10.1161/CIRCULATIONAHA.114.013748 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AY0PW UT WOS:000347299900017 PM 25403646 ER PT J AU Song, ZR Chokshi, DA AF Song, Zirui Chokshi, Dave A. TI The Role of Private Payers in Payment Reform SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Song, Zirui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Song, Zirui] Harvard Univ, Sch Med, Boston, MA USA. [Chokshi, Dave A.] New York City Hlth & Hosp Corp, New York, NY USA. [Chokshi, Dave A.] NYU, Langone Med Ctr, Dept Populat Hlth, New York, NY USA. [Chokshi, Dave A.] NYU, Langone Med Ctr, Dept Med, New York, NY USA. RP Song, ZR (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM zirui_song@post.harvard.edu FU NIA NIH HHS [F30 AG039175] NR 9 TC 5 Z9 5 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 6 PY 2015 VL 313 IS 1 BP 25 EP 26 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AY3IQ UT WOS:000347478000007 PM 25562259 ER PT J AU Katz, M Laffel, L AF Katz, Michelle Laffel, Lori TI Mortality in Type 1 Diabetes in the Current Era Two Steps Forward, One Step Backward SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DISEASE; POPULATION; ONSET; COMPLICATIONS; MELLITUS; RISK; CARE C1 [Katz, Michelle; Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. [Katz, Michelle; Laffel, Lori] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Laffel, Lori] Massachusetts Gen Hosp Children, Pediat Endocrinol Unit, Boston, MA USA. [Katz, Michelle; Laffel, Lori] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Laffel, L (reprint author), Joslin Diabet Ctr, Sect Pediat Adolescent & Young Adult Diabet, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836, K12DK094721, K12 DK094721, P30DK036836] NR 18 TC 6 Z9 6 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 6 PY 2015 VL 313 IS 1 BP 35 EP 36 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AY3IQ UT WOS:000347478000012 PM 25562263 ER PT J AU Orchard, TJ Nathan, DM Zinman, B Cleary, P Brillon, D Backlund, JYC Lachin, JM AF Orchard, Trevor J. Nathan, David M. Zinman, Bernard Cleary, Patricia Brillon, David Backlund, Jye-Yu C. Lachin, John M. CA DCCT EDIC Res Grp TI Association Between 7 Years of Intensive Treatment of Type 1 Diabetes and Long-term Mortality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ALL-CAUSE MORTALITY; GLOMERULAR-FILTRATION-RATE; POPULATION-BASED COHORT; PITTSBURGH EPIDEMIOLOGY; FOLLOW-UP; COMPLICATIONS; MELLITUS; INTERVENTIONS; DISEASE; TRENDS AB IMPORTANCE Whether mortality in type 1 diabetes mellitus is affected following intensive glycemic therapy has not been established. OBJECTIVE To determine whether mortality differed between the original intensive and conventional treatment groups in the long-term follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. DESIGN, SETTING, AND PARTICIPANTS After the DCCT (1983-1993) ended, participants were followed up in a multisite (27 US and Canadian academic clinical centers) observational study (Epidemiology of Diabetes Control and Complications [EDIC]) until December 31, 2012. Participants were 1441 healthy volunteers with diabetes mellitus who, at baseline, were 13 to 39 years of age with 1 to 15 years of diabetes duration and no or early microvascular complications, and without hypertension, preexisting cardiovascular disease, or other potentially life-threatening disease. INTERVENTIONS AND EXPOSURES During the clinical trial, participants were randomly assigned to receive intensive therapy (n = 711) aimed at achieving glycemia as close to the nondiabetic range as safely possible, or conventional therapy (n = 730) with the goal of avoiding symptomatic hypoglycemia and hyperglycemia. At the end of the DCCT, after a mean of 6.5 years, intensive therapy was taught and recommended to all participants and diabetes care was returned to personal physicians. MAIN OUTCOMES AND MEASURES Total and cause-specific mortality was assessed through annual contact with family and friends and through records over 27 years' mean follow-up. RESULTS Vital status was ascertained for 1429 (99.2%) participants. There were 107 deaths, 64 in the conventional and 43 in the intensive group. The absolute risk difference was -109 per 100 000 patient-years (95% CI, -218 to -1), with lower all-cause mortality risk in the intensive therapy group (hazard ratio [HR] = 0.67 [95% CI, 0.46-0.99]; P = .045). Primary causes of death were cardiovascular disease (24 deaths; 22.4%), cancer (21 deaths; 19.6%), acute diabetes complications (19 deaths; 17.8%), and accidents or suicide (18 deaths; 16.8%). Higher levels of glycated hemoglobin (HbA(1c)) were associated with all-cause mortality (HR = 1.56 [95% CI, 1.35-1.81 per 10% relative increase in HbA(1c)]; P < .001), as well as the development of albuminuria (HR = 2.20 [95% CI, 1.46-3.31]; P < .001). CONCLUSIONS AND RELEVANCE After a mean of 27 years' follow-up of patients with type 1 diabetes, 6.5 years of initial intensive diabetes therapy was associated with a modestly lower all-cause mortality rate when compared with conventional therapy. C1 [Orchard, Trevor J.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Zinman, Bernard] Univ Toronto, Mt Sinai Hosp, Lunefeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Cleary, Patricia; Backlund, Jye-Yu C.; Lachin, John M.] George Washington Univ, Biostat Ctr, Rockville, MD USA. [Brillon, David] Cornell Univ, Med Ctr, New York, NY 10021 USA. RP Orchard, TJ (reprint author), Univ Pittsburgh, 3512 Fifth Ave,Room 207, Pittsburgh, PA 15213 USA. EM tjo@pitt.edu RI Zinman, Bernard/E-7266-2013; OI orchard, trevor/0000-0001-9552-3215; Lachin, John/0000-0001-9838-2841 FU Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease [U01 DK094176, U01 DK094157]; National Eye Institute; National Institute of Neurological Disorders and Stroke; General Clinical Research Centers Program; Clinical Translational Science Center Program, Bethesda, Maryland FX The DCCT/EDIC has been supported by U01 cooperative agreement grants (1982-1993 and 2011-2016) and contracts (1982-2011) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (grants U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and the Clinical Translational Science Center Program (2006-present), Bethesda, Maryland. The following industry contributors provided free or discounted supplies or equipment to support participants' adherence to the study: Abbott Diabetes Care (Alameda, CA), Animas (Westchester, PA), Bayer Diabetes Care (North America Headquarters, Tarrytown, NY), Becton Dickinson (Franklin Lakes, NJ), Eli Lilly (Indianapolis, IN), Extend Nutrition (St. Louis, MO), Lifescan (Milpitas, CA), Medtronic Diabetes (Minneapolis, MN), Nipro Home Diagnostics (Ft. Lauderdale, FL), Nova Diabetes Care (Billerica, MA), Omron (Shelton, CT), OmniPod Insulin Management System (Bedford, MA), Perrigo Diabetes Care (Allegan, MI), Roche Diabetes Care (Indianapolis, IN), and sanofi-aventis (Bridgewater NJ). NR 31 TC 84 Z9 87 U1 3 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 6 PY 2015 VL 313 IS 1 BP 45 EP 53 DI 10.1001/jama.2014.16107 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AY3IQ UT WOS:000347478000014 ER PT J AU Kostis, WJ Pentakota, SR Morerya, AE AF Kostis, William J. Pentakota, Sri Ram Morerya, Abel E. TI Risk Profile of Clinical Trial Participants SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Kostis, William J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pentakota, Sri Ram; Morerya, Abel E.] Rutgers Robert Wood Johnson Med Sch, Cardiovasc Inst, New Brunswick, NJ USA. RP Kostis, WJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM wkostis@mgh.harvard.edu NR 3 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 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 6 PY 2015 VL 313 IS 1 BP 93 EP 94 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AY3IQ UT WOS:000347478000027 PM 25562277 ER PT J AU Zhang, ZG Kolm, P Grau-Sepulveda, MV Ponirakis, A O'Brien, SM Klein, LW Shaw, RE Mckay, C Shahian, DM Grover, FL Mayer, JE Garratt, KN Hlatky, M Edwards, FH Weintraub, WS AF Zhang, Zugui Kolm, Paul Grau-Sepulveda, Maria V. Ponirakis, Angelo O'Brien, Sean M. Klein, Lloyd W. Shaw, Richard E. Mckay, Charles Shahian, David M. Grover, Frederick L. Mayer, John E. Garratt, Kirk N. Hlatky, Mark Edwards, Fred H. Weintraub, William S. TI Cost-Effectiveness of Revascularization Strategies The ASCERT Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE coronary artery bypass graft; incremental cost-effectiveness ratio; percutaneous coronary intervention; stable ischemic heart disease ID PERCUTANEOUS CORONARY INTERVENTION; CARDIOVASCULAR DATA REGISTRY; ADULT CARDIAC-SURGERY; DRUG-ELUTING STENTS; AMERICAN-COLLEGE; QUALITY MEASUREMENT; HEART-ASSOCIATION; DISEASE; SELECTION; SOCIETY AB BACKGROUND ASCERT (American College of Cardiology Foundation and the Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies) was a large observational study designed to compare the long-term effectiveness of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) to treat coronary artery disease (CAD) over 4 to 5 years. OBJECTIVES This study examined the cost-effectiveness of CABG versus PCI for stable ischemic heart disease. METHODS The Society of Thoracic Surgeons and American College of Cardiology Foundation databases were linked to the Centers for Medicare and Medicaid Services claims data. Costs for the index and observation period (2004 to 2008) hospitalizations were assessed by diagnosis-related group Medicare reimbursement rates; costs beyond the observation period were estimated from average Medicare participant per capita expenditure. Effectiveness was measured via mortality and life-expectancy data. Cost and effectiveness comparisons were adjusted using propensity score matching with the incremental cost-effectiveness ratio expressed as cost per quality-adjusted life-year gained. RESULTS CABG patients (n = 86,244) and PCI patients (n = 103,549) were at least 65 years old with 2- or 3-vessel coronary artery disease. Adjusted costs were higher for CABG for the index hospitalization, study period, and lifetime by $10,670, $8,145, and $11,575, respectively. Patients undergoing CABG gained an adjusted average of 0.2525 and 0.3801 life-years relative to PCI over the observation period and lifetime, respectively. The life-time incremental cost-effectiveness ratio of CABG compared to PCI was $30,454/QALY gained. CONCLUSIONS Over a period of 4 years or longer, patients undergoing CABG had better outcomes but at higher costs than those undergoing PCI. (C) 2015 by the American College of Cardiology Foundation. C1 [Zhang, Zugui; Kolm, Paul; Weintraub, William S.] Christiana Care Hlth Syst, Value Inst, Newark, DE 19718 USA. [Grau-Sepulveda, Maria V.; O'Brien, Sean M.] Duke Clin Res Inst, Dept Outcomes Hlth Econ & Qual Life, Durham, NC USA. [Ponirakis, Angelo] Amer Coll Cardiol, Dept Res Study, Washington, DC USA. [Klein, Lloyd W.] Advocate Illinois Mason Med Ctr, Cardiol Sect, Chicago, IL USA. [Shaw, Richard E.] Harbor UCLA Med Ctr, Cardiol Sect, Torrance, CA 90509 USA. [Mckay, Charles] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. [Grover, Frederick L.] Denver Dept Vet Affairs Med Ctr, Cardiol Sect, Denver, CO USA. [Mayer, John E.] Boston Childrens Hosp, Dept Cardiac Surg, Boston, MA USA. [Garratt, Kirk N.] Lenox Hill Heart & Vasc Inst New York, Dept Intervent Cardiovasc Res, New York, NY USA. [Hlatky, Mark] Stanford Univ, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. Univ Florida Shands Jacksonville, Dept Surg, Jacksonville, FL USA. RP Zhang, ZG (reprint author), Christiana Care Hlth Syst, Value Inst, Newark, DE 19718 USA. FU National Heart, Lung, and Blood Institute [RC2HL101489]; Institutional Development Award from the National Institute of General Medical Sciences of the National Institutes of Health [U54-GM104941]; Boston Scientific Corporation; DSI/Lily; CeloNova; Mayo Foundation FX This work is supported by a grant from the National Heart, Lung, and Blood Institute (#RC2HL101489) and by an Institutional Development Award from the National Institute of General Medical Sciences (#U54-GM104941) of the National Institutes of Health. Dr. Grover consults for, but does not receive fees from, Somalution. Dr. Garratt consults for The Medicines Company and Boston Scientific Corporation; and receives research support from Boston Scientific Corporation, DSI/Lily, CeloNova, and the Mayo Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Steven Nissen, MD, served as Guest Editor for this paper. NR 26 TC 9 Z9 9 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 6 PY 2015 VL 65 IS 1 BP 1 EP 11 DI 10.1016/j.jacc.2014.09.078 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AY2GI UT WOS:000347406400001 PM 25572503 ER PT J AU Tomasetti, C Marchionni, L Nowak, MA Parmigiani, G Vogelstein, B AF Tomasetti, Cristian Marchionni, Luigi Nowak, Martin A. Parmigiani, Giovanni Vogelstein, Bert TI Only three driver gene mutations are required for the development of lung and colorectal cancers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; driver mutations; somatic mutation rate; cancer incidence; cancer evolution ID MULTISTAGE CARCINOGENESIS; MYELOID-LEUKEMIA; TUMOR INITIATION; SMOKING; GENOME; MODEL; LANDSCAPES; RESISTANCE; CESSATION AB Cancer arises through the sequential accumulation of mutations in oncogenes and tumor suppressor genes. However, how many such mutations are required for a normal human cell to progress to an advanced cancer? The best estimates for this number have been provided by mathematical models based on the relation between age and incidence. For example, the classic studies of Nordling [Nordling CO (1953) Br J Cancer 7(1): 68-72] and Armitage and Doll [Armitage P, Doll R (1954) Br J Cancer 8(1): 1-12] suggest that six or seven sequential mutations are required. Here, we describe a different approach to derive this estimate that combines conventional epidemiologic studies with genome-wide sequencing data: incidence data for different groups of patients with the same cancer type were compared with respect to their somatic mutation rates. In two well-documented cancer types (lung and colon adenocarcinomas), we find that only three sequential mutations are required to develop cancer. This conclusion deepens our understanding of the process of carcinogenesis and has important implications for the design of future cancer genome-sequencing efforts. C1 [Tomasetti, Cristian] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Div Biostat & Bioinformat,Dept Oncol, Baltimore, MD 21205 USA. [Tomasetti, Cristian] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Marchionni, Luigi] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Canc Biol Program, Baltimore, MD 21205 USA. [Nowak, Martin A.] Harvard Univ, Dept Math, Program Evolutionary Dynam, Cambridge, MA 02138 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Vogelstein, Bert] Johns Hopkins Univ, Sch Med, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21205 USA. [Vogelstein, Bert] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Sidney Kimmel Canc Ctr, Baltimore, MD 21205 USA. RP Tomasetti, C (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Div Biostat & Bioinformat,Dept Oncol, Baltimore, MD 21205 USA. EM ctomasetti@jhu.edu; vogelbe@jhmi.edu OI Tomasetti, Cristian/0000-0003-3277-4804 FU NIH [P30CA006973, R37CA43460]; Virginia and D. K. Ludwig Fund for Cancer Research FX We thank Donald Geman for useful comments on the manuscript. C.T. and L.M. were supported by NIH Core Grant P30CA006973 (to Johns Hopkins Kimmel Cancer Center). B.V. was supported by The Virginia and D. K. Ludwig Fund for Cancer Research and by NIH Grant R37CA43460. NR 35 TC 48 Z9 50 U1 4 U2 30 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 6 PY 2015 VL 112 IS 1 BP 118 EP 123 DI 10.1073/pnas.1421839112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2WN UT WOS:000347447100039 PM 25535351 ER PT J AU Li, WY Wu, JF Yang, JM Sun, S Chai, RJ Chen, ZY Li, HW AF Li, Wenyan Wu, Jingfang Yang, Jianming Sun, Shan Chai, Renjie Chen, Zheng-Yi Li, Huawei TI Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Notch1; beta-catenin; proliferation; hair cells; inner ear ID MOUSE INNER-EAR; SUPPORTING CELLS; ACOUSTIC TRAUMA; STEM-CELLS; TISSUE REGENERATION; BETA-CATENIN; LATERAL-LINE; IN-VIVO; EXPRESSION; MICE AB The activation of cochlear progenitor cells is a promising approach for hair cell (HC) regeneration and hearing recovery. The mechanisms underlying the initiation of proliferation of postnatal cochlear progenitor cells and their transdifferentiation to HCs remain to be determined. We show that Notch inhibition initiates proliferation of supporting cells (SCs) and mitotic regeneration of HCs in neonatal mouse cochlea in vivo and in vitro. Through lineage tracing, we identify that a majority of the proliferating SCs and mitotic-generated HCs induced by Notch inhibition are derived from the Wnt-responsive leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5(+)) progenitor cells. We demonstrate that Notch inhibition removes the brakes on the canonical Wnt signaling and promotes Lgr5(+) progenitor cells to mitotically generate new HCs. Our study reveals a new function of Notch signaling in limiting proliferation and regeneration potential of postnatal cochlear progenitor cells, and provides a new route to regenerate HCs from progenitor cells by interrupting the interaction between the Notch and Wnt pathways. C1 [Li, Wenyan; Wu, Jingfang; Sun, Shan; Li, Huawei] Fudan Univ, Dept Otorhinolaryngol, Shanghai 200032, Peoples R China. [Sun, Shan; Li, Huawei] Fudan Univ, Throat Hosp, Minist Hlth, Key Lab Hearing Sci, Shanghai 200032, Peoples R China. [Li, Huawei] Fudan Univ, Inst Biomed Sci, Inst Stem Cell & Regenerat Med, Shanghai 200032, Peoples R China. [Li, Huawei] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Li, Wenyan; Chen, Zheng-Yi] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Li, Wenyan; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Yang, Jianming] Anhui Med Univ, Affiliated Hosp 2, Dept Otorhinolaryngol, Hefei 230601, Anhui, Peoples R China. [Chai, Renjie] Southeast Univ, Jiangsu Prov Coinnovat Ctr Neuroregenerat, Nanjing 210096, Jiangsu, Peoples R China. [Chai, Renjie] Southeast Univ, Inst Life Sci, Minist Educ, Key Lab Dev Genes & Human Dis, Nanjing 210096, Jiangsu, Peoples R China. RP Chen, ZY (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM zheng-yi_chen@meei.harvard.edu; hwli@shmu.edu.cn FU 973 Program [2011CB504506, 2015CB965000]; National Natural Science Foundation of China [81230019, 81400463, 81470687, 81470692, 81371094]; Construction Program of Shanghai Committee of Science and Technology [12DZ2251700, 14DJ1400203]; Major Program of Shanghai Committee of Science and Technology [11441901000]; Frederick & Ines Yeatts Hair Cell Regeneration Grant; David-Shulsky Foundation; Bertarelli Foundation; NIH [R01 DC06908] FX This work was supported by grants from 973 Program (Grants 2011CB504506, 2015CB965000), the National Natural Science Foundation of China (Grants 81230019, 81400463, 81470687, 81470692, 81371094), the Construction Program of Shanghai Committee of Science and Technology (Grants 12DZ2251700 and 14DJ1400203), the Major Program of Shanghai Committee of Science and Technology (Grant 11441901000), a Frederick & Ines Yeatts Hair Cell Regeneration Grant, and the David-Shulsky Foundation, the Bertarelli Foundation, and NIH (Grant R01 DC06908). NR 49 TC 28 Z9 30 U1 3 U2 29 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 6 PY 2015 VL 112 IS 1 BP 166 EP 171 DI 10.1073/pnas.1415901112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2WN UT WOS:000347447100047 PM 25535395 ER PT J AU Baratta, MG Schinzel, AC Zwang, Y Bandopadhayay, P Bowman-Colin, C Kutt, J Curtis, J Piao, HY Wong, LC Kung, AL Beroukhim, R Bradner, JE Drapkin, R Hahn, WC Liu, JF Livingston, DM AF Baratta, Maria Giuseppina Schinzel, Anna C. Zwang, Yaara Bandopadhayay, Pratiti Bowman-Colin, Christian Kutt, Jennifer Curtis, Jennifer Piao, Huiying Wong, Laura C. Kung, Andrew L. Beroukhim, Rameen Bradner, James E. Drapkin, Ronny Hahn, William C. Liu, Joyce F. Livingston, David M. TI An in-tumor genetic screen reveals that the BET bromodomain protein, BRD4, is a potential therapeutic target in ovarian carcinoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ovarian cancer; in vivo screen; targeted therapy; BRD4; MYCN ID CREATINE-KINASE-B; SELECTIVE-INHIBITION; SEROUS CARCINOMA; HUMAN CANCERS; EXPRESSION; MYC; RECRUITMENT; CHROMATIN; LEUKEMIA; CELLS AB High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive form of epithelial ovarian cancer, for which few targeted therapies exist. To search for new therapeutic target proteins, we performed an in vivo shRNA screen using an established human HGSOC cell line growing either subcutaneously or intraperitoneally in immunocompromised mice. We identified genes previously implicated in ovarian cancer such as AURKA1, ERBB3, CDK2, and mTOR, as well as several novel candidates including BRD4, VRK1, and GALK2. We confirmed, using both genetic and pharmacologic approaches, that the activity of BRD4, an epigenetic transcription modulator, is necessary for proliferation/survival of both an established human ovarian cancer cell line (OVCAR8) and a subset of primary serous ovarian cancer cell strains (DFs). Among the DFs tested, the strains sensitive to BRD4 inhibition revealed elevated expression of either MYCN or c-MYC, with MYCN expression correlating closely with JQ1 sensitivity. Accordingly, primary human xenografts derived from high-MYCN or c-MYC strains exhibited sensitivity to BRD4 inhibition. These data suggest that BRD4 inhibition represents a new therapeutic approach for MYC-overexpressing HGSOCs. C1 [Baratta, Maria Giuseppina; Bandopadhayay, Pratiti; Bowman-Colin, Christian; Kutt, Jennifer; Curtis, Jennifer; Piao, Huiying; Wong, Laura C.; Beroukhim, Rameen; Bradner, James E.; Livingston, David M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Schinzel, Anna C.; Zwang, Yaara; Beroukhim, Rameen; Bradner, James E.; Drapkin, Ronny; Hahn, William C.; Liu, Joyce F.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Baratta, Maria Giuseppina; Schinzel, Anna C.; Zwang, Yaara; Bandopadhayay, Pratiti; Bowman-Colin, Christian; Kung, Andrew L.; Beroukhim, Rameen; Bradner, James E.; Drapkin, Ronny; Hahn, William C.; Liu, Joyce F.; Livingston, David M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schinzel, Anna C.; Zwang, Yaara; Bandopadhayay, Pratiti; Beroukhim, Rameen; Bradner, James E.; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM david_livingston@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016; OI Drapkin, Ronny/0000-0002-6912-6977; Kung, Andrew/0000-0002-9091-488X FU Liz Tilberis Grant; Ovarian Cancer Research Foundation, National Institutes of Health/National Cancer Institute Grant [U01 CA176058]; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation FX We thank the Broad Institute RNAi Consortium for providing shRNAs; Amanda Christie and Haig Inguilizian for technical contributions; Rhamy Zeid and Alison M. Karst for contributions in exploring the role of BRD4 in ovarian cancer; Elodie Hatchi for helpful discussions and editing of the manuscript; and Stoil D. Dimitrov and Hua Wang for critical reading of the manuscript. We thank the other D.M.L. laboratory colleagues for helpful discussions and reagents and the Lurie family imaging center and the Belfer Institute for Applied Cancer Science for excellent work. This work was funded by the Liz Tilberis Grant (to J.F.L.) and the Ann Schreiber Mentored Investigator award (to M.G.B.) from the Ovarian Cancer Research Foundation, National Institutes of Health/National Cancer Institute Grant U01 CA176058 (to W.C.H.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (R.D.), and a gift from Deborah and Robert First (to Dana-Farber Cancer Institute, R.D., and D.M.L.). NR 37 TC 35 Z9 37 U1 4 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 6 PY 2015 VL 112 IS 1 BP 232 EP 237 DI 10.1073/pnas.1422165112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2WN UT WOS:000347447100058 PM 25535366 ER PT J AU Qin, WP Pan, JP Wu, Y Bauman, WA Cardozo, C AF Qin, Weiping Pan, Jiangping Wu, Yong Bauman, William A. Cardozo, Christopher TI Anabolic steroids activate calcineurin-NFAT signaling and thereby increase myotube size and reduce denervation atrophy SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE Muscle atrophy; Myotubes; Androgens; Denervation; Calcineurin-NFAT signaling ID SKELETAL-MUSCLE HYPERTROPHY; SPINAL-CORD-INJURY; GENE-EXPRESSION; NERVE ACTIVITY; AMYLOID NEUROPATHOLOGY; CALORIE RESTRICTION; CARDIAC-HYPERTROPHY; STRIATED-MUSCLES; RECEPTOR-BINDING; CYCLOSPORINE-A AB Anabolic androgens have been shown to reduce muscle loss due to immobilization, paralysis and many other medical conditions, but the molecular basis for these actions is poorly understood. We have recently demonstrated that nandrolone, a synthetic androgen, slows muscle atrophy after nerve transection associated with down-regulation of regulator of calcineurin 2 (RCAN2), a calcineurin inhibitor, suggesting a possible role of calcineurin-NFAT signaling. To test this possibility, rat gastrocnemius muscle was analyzed at 56 days after denervation. In denervated muscle, calcineurin activity declined and NFATc4 was excluded from the nucleus and these effects were reversed by nandrolone. Similarly, nandrolone increased calcineurin activity and nuclear NFATc4 levels in cultured L6 myotubes. Nandrolone also induced cell hypertrophy that was blocked by cyclosporin A or overexpression of RCAN2. Finally protection against denervation atrophy by nandrolone in rats was blocked by cyclosporin A. These results demonstrate for the first time that nandrolone activates calcineurin-NFAT signaling, and that such signaling is important in nandrolone-induced cell hypertrophy and protection against paralysis-induced muscle atrophy. Published by Elsevier Ireland Ltd. C1 [Qin, Weiping; Pan, Jiangping; Wu, Yong; Bauman, William A.; Cardozo, Christopher] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Qin, Weiping; Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, New York, NY 10029 USA. RP Qin, WP (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences SCI, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM weiping.qin@mssm.edu; Chris.cardozo@mssm.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service [B4162C, B3347K, F6997R, B0687R, B1313-R] FX We thank Kel Morin for critical reading of the manuscript and Jianwei Hou for assistance with the animal studies. Sources of research support: The Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service grants B4162C, B3347K, F6997R, B0687R and B1313-R. NR 59 TC 3 Z9 3 U1 1 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 5 PY 2015 VL 399 IS C BP 336 EP 345 DI 10.1016/j.mce.2014.09.025 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CA4MI UT WOS:000348877700036 PM 25450864 ER PT J AU Peng, SW Wang, JW Karanam, B Wang, CG Huh, WK Alvarez, RD Pai, SI Hung, CF Wu, TC Roden, RBS AF Peng, Shiwen Wang, Joshua W. Karanam, Balasubramanyam Wang, Chenguang Huh, Warner K. Alvarez, Ronald D. Pai, Sara I. Hung, Chien-fu Wu, T. -C. Roden, Richard B. S. TI Sequential Cisplatin Therapy and Vaccination with HPV16 E6E7L2 Fusion Protein in Saponin Adjuvant GPI-0100 for the Treatment of a Model HPV16+Cancer SO PLOS ONE LA English DT Article ID VULVAL INTRAEPITHELIAL NEOPLASIA; PHASE-II TRIAL; HUMAN-PAPILLOMAVIRUS VACCINES; VIRUS-LIKE PARTICLE; DNA VACCINATION; CERVICAL-CANCER; TA-CIN; MUCOSAL VACCINATION; ANTITUMOR IMMUNITY; HEALTHY-VOLUNTEERS AB Clinical studies suggest that responses to HPV16 E6E7L2 fusion protein (TA-CIN) vaccination alone are modest, and GPI-0100 is a well-tolerated, potent adjuvant. Here we sought to optimize both the immunogenicity of TA-CIN via formulation with GPI-0100 and treatment of HPV16+ cancer by vaccination after cisplatin chemotherapy. HPV16 neutralizing serum antibody titers, CD4+ T cell proliferative and E6/E7-specific CD8+ T cell responses were significantly enhanced when mice were vaccinated subcutaneously (s.c.) or intramuscularly (i.m.) with TA-CIN formulated with GPI-0100. Vaccination was tested for therapy of mice bearing syngeneic HPV16 E6/E7+ tumors (TC-1) either in the lung or subcutaneously. Mice treated with TA-CIN/GPI-0100 vaccination exhibited robust E7-specific CD8+ T cell responses, which were associated with reduced tumor burden in the lung, whereas mice receiving either component alone were similar to controls. Since vaccination alone was not sufficient for cure, mice bearing s.c. TC-1 tumor were first treated with two doses of cisplatin and then vaccinated. Vaccination with TA-CIN/GPI-0100 i.m. substantially retarded tumor growth and extended survival after cisplatin therapy. Injection of TA-CIN alone, but not GPI-0100, into the tumor (i.t.) was similarly efficacious after cisplatin therapy, but the mice eventually succumbed. However, tumor regression and extended remission was observed in 80% of the mice treated with cisplatin and then intra-tumoral TA-CIN/GPI-0100 vaccination. These mice also exhibited robust E7-specific CD8+ T cell and HPV16 neutralizing antibody responses. Thus formulation of TA-CIN with GPI-0100 and intra-tumoral delivery after cisplatin treatment elicits potent therapeutic responses in a murine model of HPV16+ cancer. C1 [Peng, Shiwen; Wang, Joshua W.; Karanam, Balasubramanyam; Hung, Chien-fu; Wu, T. -C.; Roden, Richard B. S.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. [Wang, Chenguang] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Hung, Chien-fu; Wu, T. -C.; Roden, Richard B. S.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21205 USA. [Wu, T. -C.; Roden, Richard B. S.] Johns Hopkins Univ, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. [Huh, Warner K.; Alvarez, Ronald D.] Univ Alabama Birmingham, Div Gynecol Oncol, Birmingham, AL USA. [Karanam, Balasubramanyam] Tuskegee Univ, Carver Res Fdn, Dept Biol, Tuskegee, AL 36088 USA. [Karanam, Balasubramanyam] Tuskegee Univ, Carver Res Fdn, Ctr Canc Res, Tuskegee, AL 36088 USA. [Pai, Sara I.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Roden, RBS (reprint author), Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. EM roden@jhmi.edu FU V foundation; Public Health Service [P50 CA098252, RO1 CA133749, CA118790] FX The study was funded by grants from the V foundation (www.jimmyv.org) to SP and RBSR, and Public Health Service (grants.nih.gov) grants P50 CA098252 to TCW, RO1 CA133749 to WKH, and CA118790 to RBSR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 7 Z9 8 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 5 PY 2015 VL 10 IS 1 AR e116389 DI 10.1371/journal.pone.0116389 PG 25 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ3BG UT WOS:000348102200016 PM 25560237 ER PT J AU Santavirta, T Santavirta, N Betancourt, TS Gilman, SE AF Santavirta, Torsten Santavirta, Nina Betancourt, Theresa S. Gilman, Stephen E. TI Long term mental health outcomes of Finnish children evacuated to Swedish families during the second world war and their non-evacuated siblings: cohort study SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID WORLD-WAR-II; UNACCOMPANIED REFUGEE CHILDREN; PSYCHOSOCIAL SUPPORT; ADULT DEPRESSION; BIRTH COHORT; RISK-FACTORS; FOLLOW-UP; CHILDHOOD; DISORDERS; CONFLICT AB Objectives To compare the risks of admission to hospital for any type of psychiatric disorder and for four specific psychiatric disorders among adults who as children were evacuated to Swedish foster families during the second world war and their non-evacuated siblings, and to evaluate whether these risks differ between the sexes. Design Cohort study. Setting National child evacuation scheme in Finland during the second world war. Participants Children born in Finland between 1933 and 1944 who were later included in a 10% sample of the 1950 Finnish census ascertained in 1997 (n=45 463; women: n=22 021; men: n=23 442). Evacuees in the sample were identified from war time government records. Main outcome measure Adults admitted to hospital for psychiatric disorders recorded between 1971 and 2011 in the Finnish hospital discharge register. Methods We used Cox proportional hazards models to estimate the association between evacuation to temporary foster care in Sweden during the second world war and admission to hospital for a psychiatric disorder between ages 38 and 78 years. Fixed effects methods were employed to control for all unobserved social and genetic characteristics shared among siblings. Results Among men and women combined, the risk of admission to hospital for a psychiatric disorder did not differ between Finnish adults evacuated to Swedish foster families and their non-evacuated siblings (hazard ratio 0.89, 95% confidence interval 0.64 to 1.26). Evidence suggested a lower risk of admission for any mental disorder (0.67, 0.44 to 1.03) among evacuated men, whereas for women there was no association between evacuation and the overall risk of admission for a psychiatric disorder (1.21, 0.80 to 1.83). When admissions for individual psychiatric disorders were analyzed, evacuated girls were significantly more likely than their non-evacuated sisters to be admitted to hospital for a mood disorder as an adult (2.19, 1.10 to 4.33). Conclusions The Finnish evacuation policy was not associated with an increased overall risk of admission to hospital for a psychiatric disorder in adulthood among former evacuees. In fact, evacuation was associated with a marginally reduced risk of admission for any psychiatric disorder among men. Among women who had been evacuated, however, the risk of being admitted to hospital for a mood disorder was increased. C1 [Santavirta, Torsten] Stockholm Univ, Swedish Inst Social Res, SE-10691 Stockholm, Sweden. [Santavirta, Nina] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Betancourt, Theresa S.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Dept Social & Behav Sci,Dept Psychiat, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Dept Epidemiol,Dept Psychiat, Boston, MA 02115 USA. RP Santavirta, T (reprint author), Stockholm Univ, Swedish Inst Social Res, SE-10691 Stockholm, Sweden. EM torsten.santavirta@sofi.su.se RI Santavirta, Torsten/C-3918-2014; Gilman, Stephen/E-7632-2010 OI Santavirta, Torsten/0000-0001-6613-3410; Gilman, Stephen/0000-0002-8331-6419 FU Academy of Finland; National Institutes of Health [MH087544]; Signe and Ane Gyllenberg Foundation; Tore Browaldh Foundation; Siamon Foundation FX This work was supported by the Academy of Finland, National Institutes of Health (grant MH087544), and the Signe and Ane Gyllenberg Foundation. TS received additional support from the Tore Browaldh Foundation and the Siamon Foundation. NR 62 TC 4 Z9 4 U1 2 U2 15 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD JAN 5 PY 2015 VL 350 AR g7753 DI 10.1136/bmj.g7753 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AZ3LU UT WOS:000348129900003 PM 25569841 ER PT J AU Jenkins, JA Gordon, AJ AF Jenkins, Jennifer A. Gordon, Adam J. TI Substance Use Disorder Prevention and Treatment in Stigmatized Patient Populations: Ripe for Innovation SO SUBSTANCE ABUSE LA English DT Editorial Material C1 [Jenkins, Jennifer A.] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC, Pittsburgh, PA 15240 USA. [Gordon, Adam J.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,Bldg 30, Pittsburgh, PA 15240 USA. EM adam.gordon@va.gov NR 4 TC 0 Z9 0 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD JAN 2 PY 2015 VL 36 IS 1 BP 1 EP 2 DI 10.1080/08897077.2015.1009266 PG 2 WC Substance Abuse SC Substance Abuse GA CD7MW UT WOS:000351275600001 PM 25607933 ER PT J AU Rittmueller, SE Frey, MS Williams, EC Sun, HL Bryson, CL Bradley, KA AF Rittmueller, Stacey E. Frey, Madeleine S. Williams, Emily C. Sun, Haili Bryson, Chris L. Bradley, Katharine A. TI Association Between Alcohol Use and Cardiovascular Self-Care Behaviors Among Male Hypertensive Veterans Affairs Outpatients: A Cross-Sectional Study SO SUBSTANCE ABUSE LA English DT Article DE Alcohol; cardiovascular; hypertension; self-care ID RANDOMIZED CONTROLLED-TRIALS; SERVICES TASK-FORCE; BLOOD-PRESSURE; SCREENING SCORES; PROBLEM DRINKING; UNITED-STATES; AUDIT-C; CONSUMPTION; RISK; POPULATION AB Background: Alcohol use is associated with health behaviors that impact cardiovascular outcomes in patients with hypertension, including avoiding salt, exercising, weight management, and not smoking. This study examined associations between varying levels of alcohol use and self-reported cardiovascular health behaviors among hypertensive Veterans Affairs (VA) outpatients. Methods: Male outpatients with self-reported hypertension from 7 VA sites who returned mailed questionnaires (N = 11,927) were divided into 5 levels of alcohol use: nondrinking, low-level use, and mild, moderate, and severe alcohol misuse based on AUDIT-C (Alcohol Use Disorders Identification Test-Consumption) scores (0, 1-3, 4-5, 6-7, and 8-12, respectively). For each category, adjusted logistic regression models estimated the prevalence of patients who self-reported avoiding salt, exercising, controlling weight, or not smoking, and the composite of all four. Results: Increasing level of alcohol use was associated with decreasing prevalence of avoiding salt, controlling weight, not smoking, and the combination of all 4 behaviors (P values all <.001). A linear trend was not observed for exercise (P =.83), which was most common among patients with mild alcohol misuse (P =.01 relative to nondrinking). Conclusions: Alcohol consumption is inversely associated with adherence to cardiovascular self-care behaviors among hypertensive VA outpatients. Clinicians should be especially aware of alcohol use level among hypertensive patients. C1 [Rittmueller, Stacey E.] Pacific Northwest Univ Hlth Sci, Yakima, WA USA. [Frey, Madeleine S.; Bradley, Katharine A.] Grp Hlth Res Inst, Ctr Community Hlth & Evaluat, Seattle, WA USA. [Williams, Emily C.; Sun, Haili; Bryson, Chris L.] Vet Affairs VA Puget Sound Hlth Care Syst, Denver Seattle Ctr Innovat Vet Ctr & Value Driven, Seattle, WA USA. [Williams, Emily C.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bryson, Chris L.] Vet Affairs VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. [Bryson, Chris L.; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. [Bradley, Katharine A.] Vet Affairs VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, Denver Seattle Ctr Innovat Vet Ctr & Value Driven, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Emily.williams3@va.gov FU VA HSRD IIR grant [IAC 05-206-1]; VA Health Services Research and Development [CDA 12-276]; VA Center of Excellence for Substance Abuse Treatment and Education; VA HSRD grants [SDR96-002, IIR99-376]; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI) FX This work was funded by VA HSR&D IIR grant IAC 05-206-1 and conducted with support from VA Health Services Research and Development and VA Center of Excellence for Substance Abuse Treatment and Education. The VA Ambulatory Care Quality Improvement Project (ACQUIP) was funded by VA HSR&D grants SDR96-002 and IIR99-376. Dr. Williams is supported by a Career Development Award from VA Health Services Research & Development (CDA 12-276) and is an investigator with the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work at Washington University in St. Louis. IRI is supported through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI). Views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the University of Washington, or Group Health Research Institute. NR 37 TC 2 Z9 2 U1 1 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD JAN 2 PY 2015 VL 36 IS 1 BP 6 EP 12 DI 10.1080/08897077.2014.932318 PG 7 WC Substance Abuse SC Substance Abuse GA CD7MW UT WOS:000351275600003 PM 24964087 ER PT J AU Pollick, SA Beatty, JR Sokol, RJ Strickler, RC Chang, G Svikis, DS Tzilos, GK Ondersma, SJ AF Pollick, Sarah A. Beatty, Jessica R. Sokol, Robert J. Strickler, Ronald C. Chang, Grace Svikis, Dace S. Tzilos, Golfo K. Ondersma, Steven J. TI Acceptability of a Computerized Brief Intervention for Alcohol Among Abstinent But At-Risk Pregnant Women SO SUBSTANCE ABUSE LA English DT Article DE technology; pregnancy; intervention programs; Alcohol/alcoholism; mixed-methods research ID PRIMARY-HEALTH-CARE; GENERAL-PRACTITIONERS; BEHAVIOR; CLINICIAN; DRINKING; TRIAL AB Background: Limitations in time and training have hindered widespread implementation of alcohol-based interventions in prenatal clinics. Also, despite the possibility of underreporting or relapse, many at-risk women report that they quit drinking after pregnancy confirmation so that interventions focusing on current drinking may seem unnecessary. The Computerized Brief Intervention for Alcohol Use in Pregnancy (C-BIAP) was designed to (a) be implemented via a handheld device in prenatal clinics, and (b) use a modified brief intervention strategy with women who screen at-risk but report no current drinking. Methods: The authors administered the C-BIAP to 18 T-ACE (Tolerance, Annoyance, Cut Down, and Eye Opener)-positive pregnant African American women who provided quantitative and qualitative feedback. Results: The C-BIAP received high ratings of acceptability; qualitative feedback was also positive overall and suggested good acceptance of abstinence themes. Conclusions: Technology may be a feasible and acceptable method for brief intervention delivery with pregnant women who do not report current drinking. C1 [Pollick, Sarah A.; Beatty, Jessica R.; Ondersma, Steven J.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48202 USA. [Sokol, Robert J.] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Detroit, MI 48202 USA. [Strickler, Ronald C.] Henry Ford Hlth Syst, Gynecol Obstet & Womens Hlth, Detroit, MI USA. [Chang, Grace] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Chang, Grace] VA Boston Healthcare Syst, Addict Psychiat Inpatient Program, Boston, MA USA. [Chang, Grace] VA Boston Healthcare Syst, Residential Program, Boston, MA USA. [Svikis, Dace S.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Svikis, Dace S.] Virginia Commonwealth Univ, Inst Womens Hlth, Richmond, VA USA. [Tzilos, Golfo K.] Brown Univ, Dept Psychiat & Human Behav & Behav & Social Sci, Providence, RI 02912 USA. RP Ondersma, SJ (reprint author), Wayne State Univ, Dept Psychiat & Behav Neurosci, 71 E Ferry Ave, Detroit, MI 48202 USA. EM s.ondersma@wayne.edu FU National Institute on Alcohol Abuse and Alcoholism [AA 20056] FX This research was conducted with support from the National Institute on Alcohol Abuse and Alcoholism (grant AA 20056). The National Institutes of Health had no role in the conduct of the study, data analysis, or preparation of the manuscript. NR 26 TC 6 Z9 6 U1 3 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD JAN 2 PY 2015 VL 36 IS 1 BP 13 EP 20 DI 10.1080/08897077.2013.857631 PG 8 WC Substance Abuse SC Substance Abuse GA CD7MW UT WOS:000351275600004 PM 24266770 ER PT J AU Collins, SE Duncan, MH Smart, BF Saxon, AJ Malone, DK Jackson, TR Ries, RK AF Collins, Susan E. Duncan, Mark H. Smart, Brian F. Saxon, Andrew J. Malone, Daniel K. Jackson, T. Ron Ries, Richard K. TI Extended-Release Naltrexone and Harm Reduction Counseling for Chronically Homeless People With Alcohol Dependence SO SUBSTANCE ABUSE LA English DT Article DE extended-release naltrexone; Alcohol dependence; homelessness; harm reduction ID SUBSTANCE-ABUSE TREATMENT; COGNITIVE-BEHAVIORAL TREATMENT; RANDOMIZED CONTROLLED-TRIALS; HOUSING 1ST; ETHYL GLUCURONIDE; PHARMACOTHERAPY TRIALS; CONTROLLED DRINKING; MENTAL-ILLNESS; HEAVY DRINKING; USE DISORDERS AB Background: Abstinence-based alcohol interventions are minimally desirable to and effective for chronically homeless individuals with alcohol dependence who have multimorbidity and high publicly funded service utilization and associated costs. Lower-barrier, patient-centered combined pharmacobehavioral interventions may more effectively treat this population. Harm reduction counseling involves a nonjudgmental, empathic style and patient-driven goal setting that requires neither abstinence nor use reduction. Extended-release naltrexone (XR-NTX), a monthly injectable formulation of an opioid receptor antagonist, reduces craving, is safe and effective for active drinkers, and may thereby support harm reduction goal setting. The aims of this 12-week, single-arm pilot were to initially document some aspects of feasibility, acceptability, and alcohol outcomes following XR-NTX administration and harm reduction counseling for chronically homeless individuals with alcohol dependence. Methods: Participants were currently/formerly chronically homeless, alcohol-dependent individuals (N = 31) from 2 community-based agencies in the US Pacific Northwest. Measures included self-reported alcohol craving, quantity/frequency, problems, and biomarkers (ethyl glucuronide [EtG], liver transaminases). XR-NTX and harm reduction counseling were administered monthly over the 3-month treatment course. Results: Of the 45 individuals approached, 43 were interested in participation. The first injection was received by 31 participants, and 24 complied with all study procedures. Participants reported the treatment was acceptable. Participants evinced decreases in alcohol craving (33%), typical (25%) and peak (34%) use, frequency (17%), problems (60%), and EtG from the baseline to the 12-week follow-up (Ps < .05). Conclusions: XR-NTX and harm reduction counseling are promising means of supporting reductions in alcohol use and alcohol-related harm among chronically homeless, alcohol-dependent individuals. C1 [Collins, Susan E.; Duncan, Mark H.; Smart, Brian F.; Saxon, Andrew J.; Ries, Richard K.] Univ Washington, Harborview Med Ctr, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Saxon, Andrew J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Malone, Daniel K.] Downtown Emergency Serv Ctr, Seattle, WA USA. [Jackson, T. Ron] Evergreen Treatment Serv, Seattle, WA USA. RP Collins, SE (reprint author), Univ Washington, Harborview Med Ctr, Dept Psychiat & Behav Sci, 325 Ninth Ave,Box 359911, Seattle, WA 98104 USA. EM collinss@uw.edu FU Alcohol and Drug Abuse Institute; Center for Healthcare Improvement for Addictions, Mental Illness and Medically Vulnerable Populations (CHAMMP); National Institute on Alcohol Abuse and Alcoholism [K22AA018384] FX This research was supported by small grants from the Alcohol and Drug Abuse Institute (Principal Investigator [PI]: Collins) and the Center for Healthcare Improvement for Addictions, Mental Illness and Medically Vulnerable Populations (CHAMMP; PI: Collins) as well as a Career Transition Award from the National Institute on Alcohol Abuse and Alcoholism (K22AA018384; PI: Collins). These agencies were not directly involved in the work reported on in the article or in the composition of the submission. Dr. Saxon serves on the Scientific Advisory Board for Alkermes and as speaker for Reckitt Benckiser. Dr. Ries serves as speaker for Alkermes, Janssen Pharmaceuticals, and has served in the past as speaker for Reckitt Benckiser. All other authors declare that they have no conflicts of interest pertaining to this article. NR 100 TC 6 Z9 6 U1 2 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD JAN 2 PY 2015 VL 36 IS 1 BP 21 EP 33 DI 10.1080/08897077.2014.904838 PG 13 WC Substance Abuse SC Substance Abuse GA CD7MW UT WOS:000351275600005 PM 24779575 ER PT J AU Gopal, GJ Pal, J Kumar, A Mukhopadhyay, G AF Gopal, Gopal Jee Pal, Jagannath Kumar, Awanish Mukhopadhyay, Gauranga TI C-terminal domain of CagX is responsible for its interaction with CagT protein of Helicobacter pylri type IV secretion system SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE H. pylori; TFSS; CagT/CagX; Interaction; Yeast-two-hybrid system ID AGROBACTERIUM-TUMEFACIENS; PATHOGENICITY ISLAND; CONJUGATION SYSTEMS; HOST-CELLS; PYLORI; APPARATUS; TRANSLOCATION; SURFACE; GENES; YEAST AB Helicobacter pylori are the well known human pathogen associated with gastric cancer and peptic ulcer. Pathogenesis is mainly due to the presence of 40 kb cagPAI (cog Pathogenicity Island) region that encodes the type IV secretion system (TFSS) consisting of a cytoplasmic part, a middle part/core complex (spans from inner membrane to outer membrane), and an outer membrane associated part. CagX and CagT are two important proteins of TFSS that have homology with virB9 and virB7 of Agrobacterium tumefaciens TFSS. In this study, we have shown that the CagX and CagT interact directly by using co-immunoprecipitation of endogenous CagX and CagT and MBP pull down assay. We further authenticate this observation using yeast two-hybrid assay and co-expression of both the protein coding gene in Escherichia coli. We also observed that the C-terminal region of CagX is important for CagT interaction. We reconfirm that CagT depends on CagX for its stabilization. These observations could contribute in overall visualization of assembly and architecture of TFSS because protein-protein interactions among Cag proteins are likely to have an important role in assembly. Thorough understanding about architecture and mechanism of action of cag-TFSS may lead to design controlled drug delivery system. (C) 2014 Elsevier Inc. All rights reserved. C1 [Gopal, Gopal Jee; Pal, Jagannath; Mukhopadhyay, Gauranga] Jawaharlal Nehru Univ, Special Ctr Mol Med, New Delhi 110067, India. [Gopal, Gopal Jee] Maharaja Sayajirao Univ Baroda, Dept Biochem, Vadodara, Gujarat, India. [Pal, Jagannath] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kumar, Awanish] Natl Inst Technol, Dept Biotechnol, Raipur, Chhattisgarh, India. RP Gopal, GJ (reprint author), Maharaja Sayajirao Univ Baroda, Dept Biochem, Vadodara, Gujarat, India. EM gopaljigopal@rediffmail.com; garunga@hotmail.com FU Council for Scientific and Industrial Research New Delhi, India FX GJG acknowledges Council for Scientific and Industrial Research New Delhi, India for fellowship and funding. Authors are thankful to Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, Dept. of Biochemistry, M.S. University, Vadodara, Dept. of Biotechnology, NIT, Raipur, India. NR 23 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 2 PY 2015 VL 456 IS 1 BP 98 EP 103 DI 10.1016/j.bbrc.2014.11.041 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AZ8RZ UT WOS:000348483600016 PM 25446105 ER PT J AU Barry, WT Perou, CM Marcom, PK Carey, LA Ibrahim, JG AF Barry, William T. Perou, Charles M. Marcom, P. Kelly Carey, Lisa A. Ibrahim, Joseph G. TI The Use of Bayesian Hierarchical Models for Adaptive Randomization in Biomarker-Driven Phase II Studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Response adaptive; Integral biomarkers; Phase II trials ID BIASED COIN DESIGNS; HUMAN BREAST-TUMORS; PLAY-WINNER RULE; CLINICAL-TRIALS; PERSONALIZED MEDICINE; MOLECULAR PORTRAITS; LUNG-CANCER; GENE; THERAPY; INFERENCE AB The role of biomarkers has increased in cancer clinical trials such that novel designs are needed to efficiently answer questions of both drug effects and biomarker performance. We advocate Bayesian hierarchical models for response-adaptive randomized phase II studies integrating single or multiple biomarkers. Prior selection allows one to control a gradual and seamless transition from randomized-blocks to marker-enrichment during the trial. Adaptive randomization is an efficient design for evaluating treatment efficacy within biomarker subgroups, with less variable final sample sizes when compared to nested staged designs. Inference based on the Bayesian hierarchical model also has improved performance in identifying the sub-population where therapeutics are effective over independent analyses done within each biomarker subgroup. C1 [Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Perou, Charles M.] Univ N Carolina, Dept Pathol, Chapel Hill, NC USA. [Marcom, P. Kelly] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Carey, Lisa A.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. [Ibrahim, Joseph G.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. RP Barry, WT (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave,CLS 11007, Boston, MA 02215 USA. EM bbarry@jimmy.harvard.edu OI Perou, Charles/0000-0001-9827-2247 FU NIH [1S10RR025590-01]; North Carolina Biotechnology Center [2009-IDG-1002]; V Foundation for Cancer Research; CJL Foundation FX Computation resources for simulations were through the Duke Scalable Computing Resource funded by NIH (grant number 1S10RR025590-01) and the North Carolina Biotechnology Center (grant number 2009-IDG-1002). This work was funded in part by a Partners in Excellence grant from the V Foundation for Cancer Research and by the CJL Foundation. NR 52 TC 1 Z9 1 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 2 PY 2015 VL 25 IS 1 BP 66 EP 88 DI 10.1080/10543406.2014.919933 PG 23 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AZ9CE UT WOS:000348508000006 PM 24836519 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Capturing the light: The birth of photography, a true story of genius and rivalry SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Arch & Special Collect Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Arch & Special Collect Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 EI 1746-0662 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PD JAN 2 PY 2015 VL 13 IS 1 BP 97 EP 98 DI 10.1080/17460654.2014.996328 PG 2 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA AY4KG UT WOS:000347546100008 ER PT J AU Liu, JC Ferreira, CG Yusufzai, T AF Liu, Jessica C. Ferreira, Catarina G. Yusufzai, Timur TI Human CHD2 Is a Chromatin Assembly ATPase Regulated by Its Chromo- and DNA-binding Domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE ATPase; Chromatin Remodeling; DNA-binding Protein; Epilepsy; Nucleosome; CHD2; Chromodomains ID REMODELING FACTOR; MOUSE DEVELOPMENT; SNF2 FAMILY; ISWI; ACF; NUCLEOSOMES; MUTATIONS; HELICASE; PROTEIN; IDENTIFICATION AB Background: CHD2 is a conserved ATPase and deletions of CHD2 have been linked to developmental and neurological disorders. Results: The regions flanking the ATPase domain of CHD2 confer substrate specificity and couple ATP hydrolysis to remodeling. Conclusion: CHD2 possesses nucleosome assembly activity regulated by its accessory domains. Significance: Understanding the mechanisms of chromatin remodeling is crucial for delineating how remodeling defects contribute to human diseases. Chromodomain helicase DNA-binding protein 2 (CHD2) is an ATPase and a member of the SNF2-like family of helicase-related enzymes. Although deletions of CHD2 have been linked to developmental defects in mice and epileptic disorders in humans, little is known about its biochemical and cellular activities. In this study, we investigate the ATP-dependent activity of CHD2 and show that CHD2 catalyzes the assembly of chromatin into periodic arrays. We also show that the N-terminal region of CHD2, which contains tandem chromodomains, serves an auto-inhibitory role in both the DNA-binding and ATPase activities of CHD2. While loss of the N-terminal region leads to enhanced chromatin-stimulated ATPase activity, the N-terminal region is required for ATP-dependent chromatin remodeling by CHD2. In contrast, the C-terminal region, which contains a putative DNA-binding domain, selectively senses double-stranded DNA of at least 40 base pairs in length and enhances the ATPase and chromatin remodeling activities of CHD2. Our study shows that the accessory domains of CHD2 play central roles in both regulating the ATPase domain and conferring selectivity to chromatin substrates. C1 [Liu, Jessica C.; Ferreira, Catarina G.; Yusufzai, Timur] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Liu, Jessica C.; Ferreira, Catarina G.; Yusufzai, Timur] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Liu, Jessica C.] Harvard Univ, Dept Mol & Cellular Biol, Grad Program Mol Cells & Organisms, Cambridge, MA 02138 USA. RP Yusufzai, T (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,JF520, Boston, MA 02215 USA. EM timur_yusufzai@dfci.harvard.edu RI Ferreira, Carlos Gil/G-4957-2013 NR 43 TC 5 Z9 6 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 2 PY 2015 VL 290 IS 1 BP 25 EP 34 DI 10.1074/jbc.M114.609156 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX9OG UT WOS:000347231200003 PM 25384982 ER PT J AU Chandra, A Lin, T Zhu, J Tong, W Huo, YY Jia, HR Zhang, YJ Liu, XS Cengel, K Xia, B Qin, L AF Chandra, Abhishek Lin, Tiao Zhu, Ji Tong, Wei Huo, Yanying Jia, Haoruo Zhang, Yejia Liu, X. Sherry Cengel, Keith Xia, Bing Qin, Ling TI PTH1-34 Blocks Radiation-induced Osteoblast Apoptosis by Enhancing DNA Repair through Canonical Wnt Pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Apoptosis; DNA Repair; Osteoblast; Parathyroid Hormone; Wnt Pathway; Ionizing Radiation ID PELVIC INSUFFICIENCY FRACTURES; PARATHYROID-HORMONE; BONE-FORMATION; IONIZING-RADIATION; INTERMITTENT PTH; PROTEIN-KINASE; IN-VITRO; CELLS; IRRADIATION; EXPRESSION AB Background: PTH1-34 alleviates radiation-induced osteoporosis in a preclinical radiotherapy model. Results: PTH1-34 attenuates radiation damage on osteoblasts by increasing Ku70 amount, accelerating DNA repair, and suppressing osteoblast apoptosis. Pathway analyses identify canonical Wnt pathway as an important mediator. Conclusion: PTH1-34 blocks radiation-induced osteoblast apoptosis through activation of -catenin. Significance: PTH1-34 or Wnt agonist could be possible therapy for radiation-induced osteoporosis. Focal radiotherapy for cancer patients has detrimental effects on bones within the radiation field and the primary clinical signs of bone damage include the loss of functional osteoblasts. We reported previously that daily injection of parathyroid hormone (PTH, 1-34) alleviates radiation-induced osteopenia in a preclinical radiotherapy model by improving osteoblast survival. To elucidate the molecular mechanisms, we irradiated osteoblastic UMR 106-01 cells and calvarial organ culture and demonstrated an anti-apoptosis effect of PTH1-34 on these cultures. Inhibitor assay indicated that PTH exerts its radioprotective action mainly through protein kinase A/-catenin pathway. -H2AX foci staining and comet assay revealed that PTH efficiently promotes the repair of DNA double strand breaks (DSBs) in irradiated osteoblasts via activating the -catenin pathway. Interestingly, Wnt3a alone also blocked cell death and accelerated DNA repair in primary osteoprogenitors, osteoblastic and osteocytic cells after radiation through the canonical signaling. Further investigations revealed that both Wnt3a and PTH increase the amount of Ku70, a core protein for initiating the assembly of DSB repair machinery, in osteoblasts after radiation. Moreover, down-regulation of Ku70 by siRNA abrogated the prosurvival effect of PTH and Wnt3a on irradiated osteoblasts. In summary, our results identify a novel role of PTH and canonical Wnt signaling in regulating DSB repair machinery and apoptosis in osteoblasts and shed light on using PTH1-34 or Wnt agonist as possible therapy for radiation-induced osteoporosis. C1 [Chandra, Abhishek; Lin, Tiao; Zhu, Ji; Tong, Wei; Jia, Haoruo; Liu, X. Sherry; Qin, Ling] Univ Penn, Dept Orthopaed Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Zhang, Yejia] Univ Penn, Dept Phys Med & Rehabil, Perelman Sch Med, Philadelphia, PA 19104 USA. [Zhang, Yejia] Univ Penn, Dept Orthoped Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cengel, Keith] Univ Penn, Dept Radiat Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lin, Tiao] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Orthopaed Surg, Hangzhou 310009, Zhejiang, Peoples R China. [Tong, Wei] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Orthopaed Surg, Wuhan 430022, Hubei, Peoples R China. [Xia, Bing] Rutgers State Univ, Dept Radiat Oncol, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Xia, Bing] Rutgers State Univ, Dept Radiat Oncol, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA. [Zhang, Yejia] Philadelphia Vet Affairs Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. RP Qin, L (reprint author), Univ Penn, Dept Orthopaed Surg, Perelman Sch Med, 424 Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA. EM qinling@mail.med.upenn.edu OI Liu, Xiaowei/0000-0001-7247-2232; Chandra, Abhishek/0000-0001-9423-9669 FU National Institutes of Health [R01DK095803, R01CA138804]; Penn Center for Musculoskeletal Disorder [P30AR050950]; ASBMR Junior Faculty Osteoporosis Basic Research Award; McCabe Pilot Award FX This work was supported by National Institutes of Health Grants R01DK095803 (to L. Q.) and R01CA138804 (to B. X.), Penn Center for Musculoskeletal Disorder Grant P30AR050950 (NIAMS, National Institutes of Health), the ASBMR Junior Faculty Osteoporosis Basic Research Award (to L. Q.), and the McCabe Pilot Award (to X. S. L.). NR 53 TC 6 Z9 6 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 2 PY 2015 VL 290 IS 1 BP 157 EP 167 DI 10.1074/jbc.M114.608158 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX9OG UT WOS:000347231200014 PM 25336648 ER PT J AU Greenblatt, MB Kim, JM Oh, H Park, KH Choo, MK Sano, Y Tye, CE Skobe, Z Davis, RJ Park, JM Bei, M Glimcher, LH Shim, JH AF Greenblatt, Matthew B. Kim, Jung-Min Oh, Hwanhee Park, Kwang Hwan Choo, Min-Kyung Sano, Yasuyo Tye, Coralee E. Skobe, Ziedonis Davis, Roger J. Park, Jin Mo Bei, Marianna Glimcher, Laurie H. Shim, Jae-Hyuck TI p38 alpha MAPK Is Required for Tooth Morphogenesis and Enamel Secretion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Bone Morphogenetic Protein (BMP); Microtubule-associated Protein (MAP); p38 MAPK; SMAD Transcription Factor; Tooth Development; Ameloblast; Ectodermal Dysplasia ID ACTIVATED PROTEIN-KINASE; GENE-EXPRESSION; IN-VIVO; MOUSE; BMP; APOPTOSIS; MICE; KNOT; FOLLISTATIN; DOWNSTREAM AB Background: Little is known regarding the contribution of MAPKs to the development of ectodermal appendages. Results: Mice with a deletion of p38 in ectoderm display defective secretion of dental enamel and the absence of dental cusps. Conclusion: p38 mediates critical steps in tooth morphogenesis and enamel secretion. Significance: This is the first in vivo study demonstrating that the p38 MAPK pathway is critical for tooth morphogenesis and enamel secretion. An improved understanding of the molecular pathways that drive tooth morphogenesis and enamel secretion is needed to generate teeth from organ cultures for therapeutic implantation or to determine the pathogenesis of primary disorders of dentition (Abdollah, S., Macias-Silva, M., Tsukazaki, T., Hayashi, H., Attisano, L., and Wrana, J. L. (1997) J. Biol. Chem. 272, 27678-27685). Here we present a novel ectodermal dysplasia phenotype associated with conditional deletion of p38 MAPK in ectodermal appendages using K14-cre mice (p38(K14) mice). These mice display impaired patterning of dental cusps and a profound defect in the production and biomechanical strength of dental enamel because of defects in ameloblast differentiation and activity. In the absence of p38, expression of amelogenin and (4)-integrin in ameloblasts and p21 in the enamel knot was significantly reduced. Mice lacking the MAP2K MKK6, but not mice lacking MAP2K MKK3, also show the enamel defects, implying that MKK6 functions as an upstream kinase of p38 in ectodermal appendages. Lastly, stimulation with BMP2/7 in both explant culture and an ameloblast cell line confirm that p38 functions downstream of BMPs in this context. Thus, BMP-induced activation of the p38 MAPK pathway is critical for the morphogenesis of tooth cusps and the secretion of dental enamel. C1 [Greenblatt, Matthew B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kim, Jung-Min; Oh, Hwanhee; Park, Kwang Hwan; Shim, Jae-Hyuck] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Park, Kwang Hwan] Yonsei Univ, Coll Med, Dept Microbiol, Brain Korea PLUS Project Med Sci 21, Seoul, South Korea. [Park, Kwang Hwan] Yonsei Univ, Coll Med, Dept Orthopaed Surg, Seoul, South Korea. [Choo, Min-Kyung; Sano, Yasuyo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Choo, Min-Kyung; Sano, Yasuyo] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Tye, Coralee E.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. [Skobe, Ziedonis] Forsyth Inst, Cambridge, MA 02142 USA. [Davis, Roger J.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA. [Davis, Roger J.] Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Program Mol Med, Worcester, MA 01605 USA. [Bei, Marianna] Harvard Univ, Sch Med, Shriners Burns Hosp, Dept Surg,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Glimcher, Laurie H.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. RP Greenblatt, MB (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM mag3003@med.cornell.edu; jas2060@med.cornell.edu FU National Institutes of Health [AI074957] FX This work was supported, in whole or in part, by National Institutes of Health Grant AI074957 (to J. M. P.). L. H. G. is a member of the board of directors of and holds equity in Bristol-Myers Squibb. NR 36 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 2 PY 2015 VL 290 IS 1 BP 284 EP 295 DI 10.1074/jbc.M114.599274 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX9OG UT WOS:000347231200026 PM 25406311 ER PT J AU Ou, Y Wang, SJ Jiang, L Zheng, B Gu, W AF Ou, Yang Wang, Shang-Jui Jiang, Le Zheng, Bin Gu, Wei TI p53 Protein-mediated Regulation of Phosphoglycerate Dehydrogenase (PHGDH) Is Crucial for the Apoptotic Response upon Serine Starvation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Apoptosis; Cancer Biology; Cell Death; Melanoma; Metabolism; p53; Tumor Suppressor Gene ID TUMOR-SUPPRESSOR P53; P53-INDUCIBLE REGULATOR; MALIGNANT-MELANOMA; GLUCOSE-METABOLISM; TARGET GENE; WARBURG; CANCER; GROWTH; CELLS; INHIBITION AB Background:PHGDH encodes a key metabolic enzyme in the serine biosynthesis pathway and is frequently amplified in melanomas. Results: p53 transcriptionally represses PHGDH expression. Serine starvation promotes p53-mediated apoptosis in melanomas through PHGDH suppression. Conclusion: p53-mediated repression of PHGDH enhances the apoptotic response upon serine starvation in melanoma cells. Significance: The combination of the drugs activating p53 and serine deprivation could be a better treatment for melanomas. Although p53 is frequently mutated in human cancers, about 80% of human melanomas retain wild-type p53. Here we report that PHGDH, the key metabolic enzyme that catalyzes the rate-limiting step of the serine biosynthesis pathway, is a target of p53 in human melanoma cells. p53 suppresses PHGDH expression and inhibits de novo serine biosynthesis. Notably, upon serine starvation, p53-mediated cell death is enhanced dramatically in response to Nutlin-3 treatment. Moreover, PHGDH has been found recently to be amplified frequently in human melanomas. We found that PHGDH overexpression significantly suppresses the apoptotic response, whereas RNAi-mediated knockdown of endogenous PHGDH promotes apoptosis under the same treatment. These results demonstrate an important role of p53 in regulating the serine biosynthesis pathway through suppressing PHGDH expression and reveal serine deprivation as a novel approach to sensitize p53-mediated apoptotic responses in human melanoma cells. C1 [Ou, Yang; Wang, Shang-Jui; Jiang, Le; Gu, Wei] Columbia Univ, Coll Phys & Surg, Inst Canc Genet, New York, NY 10032 USA. [Ou, Yang; Wang, Shang-Jui; Jiang, Le; Gu, Wei] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Zheng, Bin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Gu, W (reprint author), Columbia Univ Coll Phys & Surg, Dept Pathol & Cell Biol, Inst Canc Genet, 1130 St Nicholas Ave, New York, NY 10032 USA. EM wg8@columbia.edu FU NCI, National Institutes of Health [5RO1CA085533, 5RO1CA172023, 5RO1 CA166294, 2P01CA080058, R01 CA166717]; National Institutes of Health Cancer Biology Training Grant [T32-CA09503] FX This work was supported, in whole or in part, by NCI, National Institutes of Health Awards 5RO1CA085533, 5RO1CA172023, 5RO1 CA166294, 5RO1CA085533, and 2P01CA080058 (to W. G.) and R01 CA166717 (to B. Z.).; Supported by National Institutes of Health Cancer Biology Training Grant T32-CA09503. NR 37 TC 13 Z9 13 U1 0 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 2 PY 2015 VL 290 IS 1 BP 457 EP 466 DI 10.1074/jbc.M114.616359 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX9OG UT WOS:000347231200040 PM 25404730 ER PT J AU Haggerty, G Blanchard, M Baity, MR Defife, JA Stein, MB Siefert, CJ Sinclair, SJ Zodan, J AF Haggerty, Greg Blanchard, Mark Baity, Matthew R. Defife, Jared A. Stein, Michelle B. Siefert, Caleb J. Sinclair, Samuel J. Zodan, Jennifer TI Clinical Validity of a Dimensional Assessment of Self- and Interpersonal Functioning in Adolescent Inpatients SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; IV AXIS V; GLOBAL ASSESSMENT; OBJECT RELATIONS; PSYCHOLOGICAL-ASSESSMENT; MENTAL-HEALTH; ASSESSING LEVEL; LIFE-SPAN; PART I; RELIABILITY AB The Social Cognition and Object Relations Scale-Global Version (SCORS-G) is a clinical rating system assessing 8 domains of self- and interpersonal relational experience that can be applied to narrative response data (e.g., Thematic Apperception Test [TAT; Murray, 1943], early memories narratives) or oral data (e.g., psychotherapy narratives, relationship anecdotal paradigms). In this study, 72 psychiatrically hospitalized adolescents consented and were rated by their individual and group therapist using the SCORS-G. Clinicians also rated therapy engagement, personality functioning, quality of peer relationships, school functioning, global assessment of functioning (GAF), history of eating-disordered behavior, and history of nonsuicidal self-injury. SCORS-G composite ratings achieved an acceptable level of interrater reliability and were associated with theoretically predicted variables (e.g., engagement in therapy, history of nonsuicidal self-injury). SCORS-G ratings also incrementally improved the prediction of therapy engagement and global functioning beyond what was accounted for by GAF scores. This study further demonstrates the clinical utility of the SCORS-G with adolescents. C1 [Haggerty, Greg; Blanchard, Mark; Zodan, Jennifer] Nassau Univ, Med Ctr, Von Tauber Inst Global Psychiat, E Meadow, NY 11554 USA. [Baity, Matthew R.] Alliant Int Univ, Calif Sch Profess Psychol, Alhambra, CA USA. [Defife, Jared A.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Stein, Michelle B.; Sinclair, Samuel J.] Massachusetts Gen Hosp, PEaRL, Boston, MA 02114 USA. [Stein, Michelle B.; Sinclair, Samuel J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Siefert, Caleb J.] Univ Michigan Dearborn, Dept Psychol, Dearborn, MI USA. RP Haggerty, G (reprint author), Nassau Univ, Med Ctr, Von Tauber Inst Global Psychiat, 2201 Hempstead Turnpike,Box 48, E Meadow, NY 11554 USA. EM ghag541@aol.com FU NIMH NIH HHS [R21 MH097781, 1R21MH097781-01A1] NR 97 TC 2 Z9 2 U1 6 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 EI 1532-7752 J9 J PERS ASSESS JI J. Pers. Assess. PD JAN 2 PY 2015 VL 97 IS 1 BP 3 EP 12 DI 10.1080/00223891.2014.930744 PG 10 WC Psychology, Clinical; Psychology, Social SC Psychology GA AX6OU UT WOS:000347042200002 PM 25010080 ER PT J AU Gallagher, MW AF Gallagher, Matthew W. TI Treating PTSD with Cognitive-Behavioral Therapies SO COGNITIVE BEHAVIOUR THERAPY LA English DT Book Review C1 [Gallagher, Matthew W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Gallagher, Matthew W.] Boston Univ, Sch Med, Boston, MA 02130 USA. RP Gallagher, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 South Huntington Ave,Natl Ctr PTSD 116B-2, Boston, MA 02130 USA. EM mwg@bu.edu NR 1 TC 0 Z9 0 U1 2 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1650-6073 EI 1651-2316 J9 COGN BEHAV THERAPY JI Cogn. Behav. Ther. PD JAN 2 PY 2015 VL 44 IS 1 BP 86 EP 86 DI 10.1080/16506073.2014.976254 PG 1 WC Behavioral Sciences; Psychology, Clinical SC Behavioral Sciences; Psychology GA AW4QK UT WOS:000346265500010 PM 25372339 ER PT J AU Radebe, M Gounder, K Mokgoro, M Ndhlovu, ZM Mncube, Z Mkhize, L van der Stok, M Jaggernath, M Walker, BD Ndung'u, T AF Radebe, Mopo Gounder, Kamini Mokgoro, Mammekwa Ndhlovu, Zaza M. Mncube, Zenele Mkhize, Lungile van der Stok, Mary Jaggernath, Manjeetha Walker, Bruce D. Ndung'u, Thumbi TI Broad and persistent Gag-specific CD8(+) T-cell responses are associated with viral control but rarely drive viral escape during primary HIV-1 infection SO AIDS LA English DT Article DE acute HIV-1 infection; CD8(+) T cells; central CD8(+) T-cell memory responses; gag-specific responses; immune escape; persistent CD8(+) T-cell responses ID IMMUNODEFICIENCY-VIRUS TYPE-1; SET-POINT; DISEASE PROGRESSION; IMMUNE-RESPONSE; CLASS-I; VIREMIA; LOAD; EPITOPES; CD4(+); LYMPHOCYTES AB Objective: We characterized protein-specific CD8(+) T-cell immunodominance patterns during the first year of HIV-1 infection, and their impact on viral evolution and immune control. Methods: We analyzed CD8(+) T-cell responses to the full HIV-1 proteome during the first year of infection in 18 antiretroviral-naive individuals with acute HIV-1 subtype C infection, all identified prior to seroconversion. Ex-vivo and cultured interferon-gamma ELISPOT assays were performed and viruses from plasma were sequenced within defined CTL Gag epitopes. Results: Nef-specific CD8(+) T-cell responses were dominant during the first 4 weeks after infection and made up 40% of the total responses at this time; yet, by 1 year, responses against this region had declined and Gag responses made up to 47% of all T-cell responses measured. An inverse correlation between the breadth of Gag-specific responses and viral load set point was evident at 26 weeks after infection (P = 0.0081, r = -0.60) and beyond. An inverse correlation between the number of persistent responses targeting Gag and viral set point was also identified (P = 0.01, r = -0.58). Gag-specific responses detectable by the cultured ELISPOT assay correlated negatively with viral load set point (P = 0.0013, r = -0.91). Sequence evolution in targeted and nontargeted Gag epitopes in this cohort was infrequent. Conclusions: These data underscore the importance of HIV-specific CD8(+) T-cell responses, particularly to the Gag protein, in the maintenance of low viral load levels during primary infection, and show that these responses are initially poorly elicited by natural infection. These data have implications for vaccine design strategies. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Radebe, Mopo; Gounder, Kamini; Mokgoro, Mammekwa; Ndhlovu, Zaza M.; Mncube, Zenele; Mkhize, Lungile; van der Stok, Mary; Jaggernath, Manjeetha; Walker, Bruce D.; Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Radebe, Mopo; Gounder, Kamini; Walker, Bruce D.; Ndung'u, Thumbi] Nelson R Mandela Sch Med, KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Ndhlovu, Zaza M.; Walker, Bruce D.; Ndung'u, Thumbi] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Ndung'u, Thumbi] Max Planck Inst Infect Biol, Berlin, Germany. RP Ndung'u, T (reprint author), Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, 719 Umbilo Rd, Durban, South Africa. EM ndungu@ukzn.ac.za OI Ndung'u, Thumbi/0000-0003-2962-3992 FU NIH [R37AI067073]; Bill and Melinda Gates Foundation; South African Department of Science and Technology through the National Research Foundation; International AIDS Vaccine Initiative; Victor Daitz Chair in HIV/TB Research; International Early Career Scientist Award from the Howard Hughes Medical Institute; UNESCO/L'Oreal Corporate Foundation fellowship; Technology Innovation Agency of the Department of Science and Technology of South Africa; Mark and Lisa Schwartz Foundation; Fogarty International Clinical Research Fellows award FX The research was funded by NIH (R37AI067073), the Bill and Melinda Gates Foundation, the South African Department of Science and Technology through the National Research Foundation and the International AIDS Vaccine Initiative. Partial funding was also received from the Victor Daitz Chair in HIV/TB Research and an International Early Career Scientist Award from the Howard Hughes Medical Institute to TN. MR was funded by a UNESCO/L'Oreal Corporate Foundation fellowship and the Technology Innovation Agency of the Department of Science and Technology of South Africa. Additional support was provided by the Mark and Lisa Schwartz Foundation.; K.G. was the recipient of a Fogarty International Clinical Research Fellows award. NR 54 TC 10 Z9 10 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 2 PY 2015 VL 29 IS 1 BP 23 EP 33 DI 10.1097/QAD.0000000000000508 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AU4NB UT WOS:000345586900004 PM 25387316 ER PT J AU Chan, BT Weiser, SD Boum, Y Siedner, MJ Mocello, AR Haberer, JE Hunt, PW Martin, JN Mayer, KH Bangsberg, DR Tsai, AC AF Chan, Brian T. Weiser, Sheri D. Boum, Yap Siedner, Mark J. Mocello, A. Rain Haberer, Jessica E. Hunt, Peter W. Martin, Jeffrey N. Mayer, Kenneth H. Bangsberg, David R. Tsai, Alexander C. TI Persistent HIV-related stigma in rural Uganda during a period of increasing HIV incidence despite treatment expansion SO AIDS LA English DT Article DE HIV; incidence; stigma; trends; Uganda ID AIDS-RELATED STIGMA; SOUTH-AFRICA; ANTIRETROVIRAL THERAPY; CAPE-TOWN; INTERNALIZED STIGMA; TESTING SERVICES; HIV/AIDS; PEOPLE; DEPRESSION; TANZANIA AB Objective: Programme implementers have argued that the increasing availability of antiretroviral therapy (ART) will reduce the stigma of HIV. We analyzed data from Uganda to assess how HIV-related stigma has changed during a period of ART expansion. Design: Serial cross-sectional surveys. Methods: We analyzed data from the Uganda AIDS Rural Treatment Outcomes study during 2007-2012 to estimate trends in internalized stigma among people living with HIV (PLHIV) at the time of treatment initiation. We analyzed data from the Uganda Demographic and Health Surveys from 2006 to 2011 to estimate trends in stigmatizing attitudes and anticipated stigma in the general population. We fitted regression models adjusted for sociodemographic characteristics, with year of data collection as the primary explanatory variable. Results: We estimated an upward trend in internalized stigma among PLHIV presenting for treatment initiation [adjusted b = 0.18; 95% confidence interval (CI), 0.06-0.30]. In the general population, the odds of reporting anticipated stigma were greater in 2011 compared with 2006 [adjusted odds ratio (OR) = 1.80; 95% CI, 1.51-2.13], despite an apparent decline in stigmatizing attitudes (adjusted OR = 0.62; 95% CI, 0.52-0.74). Conclusion: Internalized stigma has increased over time among PLHIV in the setting of worsening anticipated stigma in the general population. Further study is needed to better understand the reasons for increasing HIV-related stigma in Uganda and its impact on HIV prevention efforts. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Chan, Brian T.; Siedner, Mark J.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Chan, Brian T.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Chan, Brian T.; Siedner, Mark J.; Haberer, Jessica E.; Mayer, Kenneth H.; Bangsberg, David R.; Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. [Weiser, Sheri D.; Hunt, Peter W.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. [Weiser, Sheri D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Boum, Yap] Epicentre, Mbarara, Uganda. [Siedner, Mark J.; Haberer, Jessica E.; Bangsberg, David R.; Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Mocello, A. Rain; Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Mayer, Kenneth H.] Fenway Hlth, Boston, MA USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Tsai, Alexander C.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. RP Chan, BT (reprint author), Brigham & Womens Hosp, 15 Francis St,PBBA 4, Boston, MA 02115 USA. EM bchan@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU US National Institutes of Health (NIH) [R01MH054907, P30AI27763, K23MH079713]; NIH [T32AI007433, K23MH099916, K23MH087228, U01CA066529, P30AI060354, K24MH087227, K23MH096620]; David Brudnoy Scholar Award; Burke Family Foundation; Merck; Gilead; Bristol Meyers Squibb FX Source of funding: The UARTO Study was funded by US National Institutes of Health (NIH) R01MH054907, P30AI27763, and K23MH079713. The authors also acknowledge the following additional sources of support: NIH T32AI007433 (B.T.C.), K23MH099916 (M.J.S.), K23MH087228 (J.E.H.), U01CA066529 (J.N.M.), P30AI060354 (K.H.M.), K24MH087227 (D.R.B.), K23MH096620 (A.C.T.), David Brudnoy Scholar Award (B.T.C.), and the Burke Family Foundation (S.D.W.). K.H.M. has also received unrestricted research grants from Merck, Gilead, and Bristol Meyers Squibb. NR 55 TC 15 Z9 15 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 2 PY 2015 VL 29 IS 1 BP 83 EP 90 DI 10.1097/QAD.0000000000000495 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AU4NB UT WOS:000345586900011 PM 25268886 ER PT J AU Andersen, L Kagee, A O'Cleirigh, C Safren, S Joska, J AF Andersen, L. Kagee, A. O'Cleirigh, C. Safren, S. Joska, J. TI Understanding the experience and manifestation of depression in people living with HIV/AIDS in South Africa SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE low- and middle-income countries; depression; South Africa; AIDS; HIV ID COMMON MENTAL-DISORDERS; VALIDATION; PREDICTORS; HEALTH AB Understanding the experience of depression in people living with HIV/AIDS (PLWH) could aid in the detection and treatment of the disorder. Yet, there is limited knowledge of the subjective experience of depression amongst PLWH in low- and middle-income countries despite high rates of this disorder in this population. In the current study, semi-structured interviews were conducted with depressed adults living with HIV attending a primary infectious disease clinic in South Africa. Interview transcripts were thematically analyzed. The construct of depression was consistent with DSM-IV criteria; however, the symptom presentation was distinctive. Somatic symptoms were most prominent in participants' initial presentations because participants perceived them as medically relevant. Affective, cognitive, and behavioral symptoms were not readily reported as participants did not perceive these symptoms as pertinent to their medical treatment. We identified several idioms of distress that could assist in screening for depression in this population. A valid, contextually developed screener for depression in PLWH awaits further investigation. Such a measure could play a key role in formulating a logistically feasible method of detection and treatment for depression in this population. C1 [Andersen, L.; Joska, J.] Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa. [Kagee, A.] Univ Stellenbosch, Dept Psychol, ZA-7600 Stellenbosch, South Africa. [O'Cleirigh, C.; Safren, S.] Harvard Univ, Sch Med, Dept Psychiat, Behav Med Serv,Massachusetts Gen Hosp,Fenway Inst, Boston, MA 02115 USA. RP Andersen, L (reprint author), Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa. EM lena.andersen@gmail.com FU NIAAA NIH HHS [R24 AA022919]; NIAID NIH HHS [P30 AI042851, P30 AI42851]; NIDA NIH HHS [R34 DA031038]; NIMH NIH HHS [K24 MH094214, 1 K24 MH094214]; Wellcome Trust NR 12 TC 1 Z9 1 U1 2 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD JAN 2 PY 2015 VL 27 IS 1 BP 59 EP 62 DI 10.1080/09540121.2014.951306 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA AS6UL UT WOS:000344397500011 PM 25303372 ER PT J AU Pecoraro, A Mimiaga, M O'Cleirigh, C Safren, SA Blokhina, E Verbitskaya, E Yaroslavtseva, T Ustinov, A Lioznov, DA Zvartau, E Krupitsky, E Woody, GE AF Pecoraro, Anna Mimiaga, Matthew O'Cleirigh, Conall Safren, Steven A. Blokhina, Elena Verbitskaya, Elena Yaroslavtseva, Tatiana Ustinov, Andrey Lioznov, Dmitry A. Zvartau, Edwin Krupitsky, Evgeny Woody, George E. TI Depression, substance use, viral load, and CD4+ count among patients who continued or left antiretroviral therapy for HIV in St. Petersburg, Russian Federation SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE attrition; retention; Russian Federation; AIDS; HIV ID PREVENTING RELAPSE; RELEASE NALTREXONE; OPIOID DEPENDENCE; LENINGRAD REGION; RANDOMIZED-TRIAL; ADHERENCE; DRUG; FACILITATORS; MEDICATION; BARRIERS AB Antiretroviral therapy (ART) became more widely available in the Russian Federation in 2006 when the Global Fund made a contribution to purchase ART with a mandate to increase numbers of patients receiving it. Funds were distributed to AIDS Centers and selected hospitals, and numbers quickly increased. Though ART is highly effective for adherent patients, dropout has been a problem; thus understanding characteristics of patients who remain on ART vs. those who leave treatment may provide information to facilitate engagement. We retrospectively assessed depression, hopelessness, substance use, viral load, and CD4+ counts of 120 patients who dropped out of ART for >= 12 months (Lost-to-Care, LTCs) and 120 who continued for >= 12 months (Engaged-in-Care, EICs). As expected, LTCs had higher viral loads and depression, lower CD4+ counts, more alcohol, heroin, and injection drug use in the past 30 days. A binary logistic regression with Center for Epidemiologic Studies Depression score, Beck Hopelessness score, whether drugs/alcohol had ever prevented them from taking ART, and past 30 days' alcohol use [chi(2)(4) = 64.27, p = .0.000] correctly classified 74.5% of participants as LTC or EIC, suggesting that integrated treatment for substance use, psychiatric, and HIV could reduce dropout and improve outcomes. C1 [Pecoraro, Anna; Woody, George E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Pecoraro, Anna; Woody, George E.] NIDA Clin Trials Network, Philadelphia, PA USA. [Mimiaga, Matthew] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mimiaga, Matthew; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [O'Cleirigh, Conall; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blokhina, Elena; Verbitskaya, Elena; Yaroslavtseva, Tatiana; Ustinov, Andrey; Lioznov, Dmitry A.; Zvartau, Edwin; Krupitsky, Evgeny] First Pavlov State Med Univ, Valdman Inst Pharmacol, St Petersburg, Russia. [Krupitsky, Evgeny] Bekhterev Res Psychoneurol Inst, St Petersburg, Russia. RP Pecoraro, A (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. EM annp@mail.med.upenn.edu RI Verbitskaya, Elena/N-3867-2015; Lioznov, Dmitry/J-2539-2013 OI Verbitskaya, Elena/0000-0003-3770-993X; Lioznov, Dmitry/0000-0003-3643-7354 FU NIDA NIH HHS [R01 DA026336]; PEPFAR NR 25 TC 8 Z9 8 U1 0 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD JAN 2 PY 2015 VL 27 IS 1 BP 86 EP 92 DI 10.1080/09540121.2014.959464 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA AS6UL UT WOS:000344397500015 PM 25264710 ER PT J AU Malave, P Sitek, A AF Malave, Peter Sitek, Arkadiusz TI Bayesian analysis of a one-compartment kinetic model used in medical imaging SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE Bayesian; estimation; positron emission tomography; kinetic model; Monte Carlo; posterior ID POSITRON-EMISSION-TOMOGRAPHY; PET AB Kinetic models are used extensively in science, engineering, and medicine. Mathematically, they are a set of coupled differential equations including a source function, otherwise known as an input function. We investigate whether parametric modeling of a noisy input function offers any benefit over the non-parametric input function in estimating kinetic parameters. Our analysis includes four formulations of Bayesian posteriors of model parameters where noise is taken into account in the likelihood functions. Posteriors are determined numerically with a Markov chain Monte Carlo simulation. We compare point estimates derived from the posteriors to a weighted non-linear least squares estimate. Results imply that parametric modeling of the input function does not improve the accuracy of model parameters, even with perfect knowledge of the functional form. Posteriors are validated using an unconventional utilization of the chi(2)-test. We demonstrate that if the noise in the input function is not taken into account, the resulting posteriors are incorrect. C1 [Malave, Peter; Sitek, Arkadiusz] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Malave, Peter; Sitek, Arkadiusz] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sitek, A (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM asitek@pet.mgh.harvard.edu OI Sitek, Arkadiusz/0000-0002-0677-4002 FU NIH [EB013180, HL106474, EB016315] FX This work was supported by NIH grants EB013180, HL106474, and EB016315. NR 16 TC 2 Z9 2 U1 1 U2 9 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 EI 1360-0532 J9 J APPL STAT JI J. Appl. Stat. PD JAN 2 PY 2015 VL 42 IS 1 BP 98 EP 113 DI 10.1080/02664763.2014.934666 PG 16 WC Statistics & Probability SC Mathematics GA AR6BT UT WOS:000343668600008 PM 25408561 ER PT J AU Hoggatt, KJ Prescott, MR Goldmann, E Tamburrino, M Calabrese, JR Liberzon, I Galea, S AF Hoggatt, Katherine J. Prescott, Marta R. Goldmann, Emily Tamburrino, Marijo Calabrese, Joseph R. Liberzon, Israel Galea, Sandro TI The Prevalence and Correlates of Risky Driving Behavior Among National Guard Soldiers SO TRAFFIC INJURY PREVENTION LA English DT Article DE combat; mental health; risky driving; military medicine; veterans of war; trauma ID GULF-WAR-I; ACTIVE-DUTY; DEPLOYMENT STRESSORS; MILITARY PERSONNEL; COMBAT RETURNEES; PTSD CHECKLIST; VETERANS; INJURY; DISORDER; PHQ-9 AB Objective: Previous studies have reported that risky driving is associated with deployment and combat exposure in military populations, but there is limited research on risky driving among soldiers in the National Guard and Reserves, a group increasingly deployed to active international conflicts. The goal of this analysis was to assess the prevalence of risky driving and its demographic, mental health, and deployment-related correlates among members of the Ohio Army National Guard (OHARNG). Methods: The study group comprised 2,616 eligible OHARNG soldiers enlisted as of June 2008, or who enlisted between June 2008 and February 2009. The main outcome of interest was the prevalence of risky driving behavior assessed using six questions: "How often do you use seat belts when you drive or ride in a car?"; "In the past 30days, how many times have you driven when you've had perhaps too much to drink?"; "In the past year, have you ever become impatient with a slow driver in the fast lane and passed them on the right?"; "In the past year have you crossed an intersection knowing that the traffic lights have already changed from yellow to red?"; "In the past year have you disregarded speed limits late at night or early in the morning?"; and "In the past year have you underestimated the speed of an oncoming vehicle when attempting to pass a vehicle in your own lane?" We fit multiple logistic regression models and derived the adjusted prevalence of risky driving behavior for soldiers with mental health conditions, deployment experience, exposure to combat or trauma, and psychosocial stressors or supports. Results: The prevalence of risky driving was higher in soldiers with a history of mental health conditions, deployment to a conflict area, deployment-related traumatic events, and combat or post-combat stressors. In contrast, the prevalence of risky driving was lower for soldiers who reported high levels of psychosocial support. Conclusions: Efforts to mitigate risky driving in military populations may be more effective if they incorporate both targeted messages to remediate dangerous learned driving behaviors and psychosocial interventions to build resilience and address underlying stressors and mental health symptoms. C1 [Hoggatt, Katherine J.] CSHIIP, VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev HSR&D, Sepulveda, CA 91343 USA. [Hoggatt, Katherine J.] UCLA Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Prescott, Marta R.; Goldmann, Emily; Galea, Sandro] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Tamburrino, Marijo] Univ Toledo, Dept Psychiat, Toledo, OH 43606 USA. [Calabrese, Joseph R.] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. [Liberzon, Israel] VA Ann Arbor, Ann Arbor, MI USA. [Liberzon, Israel] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Hoggatt, KJ (reprint author), CSHIIP, VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev HSR&D, 16111 Plummer St. 152), Sepulveda, CA 91343 USA. EM khoggatt@ucla.edu OI Liberzon, Israel/0000-0002-4990-556X FU Department of Defense Congressionally Directed Medical Research Program [W81XWH-O7-1-0409/W81XWH-10-1-0579]; Combat Mental Health Initiative; Department of Veterans Affairs, Veterans Health Administration (VA), Health Services Research and Development (HSRD) Service; VA HSR&D/QUERI Career Development Award at the VA Greater Los Angeles [CDA 11-261]; VA Office of Academic Affiliations; Department of Defense; Health Resources Services Administration; National Institute of Mental Health; Abbott; AstraZeneca; Bristol-Myers Squibb; Cephalon; Cleveland Foundation; Eli Lilly; GlaxoSmithKline; Janssen; NARSAD; Repligen; Stanley Medical Research Institute; Takeda; Wyeth FX This research was supported by Department of Defense Congressionally Directed Medical Research Program: W81XWH-O7-1-0409/W81XWH-10-1-0579, the "Combat Mental Health Initiative" and the Department of Veterans Affairs, Veterans Health Administration (VA), Health Services Research and Development (HSR&D) Service. Dr. Hoggatt was funded through a VA HSR&D/QUERI Career Development Award (CDA 11-261) at the VA Greater Los Angeles and received additional support from the VA Office of Academic Affiliations. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.; Joseph R. Calabrese has received federal funding from the Department of Defense, Health Resources Services Administration, and National Institute of Mental Health; has received research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Cleveland Foundation, Eli Lilly, GlaxoSmithKline, Janssen, NARSAD, Repligen, Stanley Medical Research Institute, Takeda, and Wyeth; has consulted to or served on advisory boards of Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Dainippon Sumitomo, EPI-Q, Inc, Forest, France Foundation, GlaxoSmithKline, Janssen, Johnson and Johnson, Lundbeck, Neurosearch, OrthoMcNeil, Otsuka, Pfizer, Repligen, Schering-Plough, Servier, Solvay, Supernus, Synosia, and Wyeth; has provided CME lectures supported by Abbott, AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen, Johnson & Johnson, Sanofi Aventis, Schering-Plough, Pfizer, Solvay, and Wyeth; and has not been on a speakers bureau for the past 8 years. Past speaker bureaus included Abbott, AstraZeneca, Eli Lilly, and GlaxoSmithKline. He has no related stock, equity, or patents. The other authors have no financial disclosures. NR 36 TC 2 Z9 2 U1 4 U2 46 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-9588 EI 1538-957X J9 TRAFFIC INJ PREV JI Traffic Inj. Prev. PD JAN 2 PY 2015 VL 16 IS 1 BP 17 EP 23 DI 10.1080/15389588.2014.896994 PG 7 WC Public, Environmental & Occupational Health; Transportation SC Public, Environmental & Occupational Health; Transportation GA AQ4ZO UT WOS:000342811100004 PM 25260973 ER PT S AU Mananga, ES AF Mananga, Eugene Stephane BE AttaUrRahman Choudhary, MI TI Mathematical Formulations Used in Solid-State NMR for Structural Biology SO APPLICATIONS OF NMR SPECTROSCOPY, VOL 2 SE Applications of NMR Spectroscopy LA English DT Article; Book Chapter DE Distance constraints; gram matrices; orientational constraints; structural biology; solid-state NMR; tensors; torsion angles ID MAGNETIC-RESONANCE SPECTRA; AVERAGE HAMILTONIAN THEORY; PROTEIN-STRUCTURE; ORIENTATIONAL RESTRAINTS; ANISOTROPIC ENVIRONMENTS; MEMBRANE-PROTEINS; SPECTROSCOPY; CONSTRAINTS; SIMULATION; GRAMICIDIN AB Recent advances in the field of structural biology, with relatively new biophysical techniques such as solid-state nuclear magnetic resonance that holds promise for determining the structures of peptides and proteins located within the cell membrane, facilitate the collection of data on the atomic structures of the biological molecules. Classical methods such as X-ray diffraction (XRD) and liquid-state NMR spectroscopy suffer from difficulties in crystallizing functional proteins in membrane environments (XRD) or too slow molecular motion for averaging of anisotropic nuclear spin interactions (liquid-state NMR) [1]. These problems have motivated the search for alternative methods such as solid-state NMR (SS-NMR). In the solid state NMR, the nuclear spin interactions are typically governed by anisotropic (orientation dependent) components in addition to the isotropic (orientation independent) components known from liquid-state NMR [2-4]. The method (SS-NMR) elucidates molecular structure and dynamics in systems not amenable to characterization by any other way. The importance of the technique stands in its ability to determine accurately intermolecular distances and molecular torsion angles. The technique has been used in systems including both microscopically ordered preparations such as membrane proteins, nanocrystalline proteins, amyloid fibrils, and also disordered or amorphous systems such as glasses. This chapter presents a view of algorithm formulation of structural biology with the mathematical foundation of the determination of protein structure from orientation constraints which highlight the solid-state NMR used as probe for the determination of peptide and protein structures. We also review the continuity conditions and torsion angles from solid-state NMR orientational restraints. Tools such as vector algebra, Gram matrices, and determinants, are used. C1 [Mananga, Eugene Stephane] Harvard Univ, Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA. [Mananga, Eugene Stephane] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging Phys, Dept Radiol, Boston, MA 02114 USA. RP Mananga, ES (reprint author), Harvard Univ, Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM emananga@pet.mgh.harvard.edu NR 56 TC 0 Z9 0 U1 1 U2 1 PU BENTHAM SCIENCE PUBL PI SHARJAH PA EXECUTIVE STE Y-2, P.O. BOX 7917, SAIF ZONE, SHARJAH, 1400 AG, U ARAB EMIRATES SN 2405-4682 BN 978-1-60805-965-2; 978-1-60805-999-7 J9 APPL NMR SPECTROSC PY 2015 VL 2 BP 220 EP 241 PG 22 WC Biochemical Research Methods; Food Science & Technology; Spectroscopy SC Biochemistry & Molecular Biology; Food Science & Technology; Spectroscopy GA BG4CO UT WOS:000388597300006 ER PT S AU Gordon, AJ Conley, JW Gordon, JM AF Gordon, Adam J. Conley, James W. Gordon, Joanne M. BE Sartorius, N Holt, RIG Maj, M TI Physical Diseases and Addictive Disorders: Associations and Implications SO COMORBIDITY OF MENTAL AND PHYSICAL DISORDERS SE Key Issues in Mental Health LA English DT Article; Book Chapter ID ACUTE MARIJUANA INTOXICATION; AMERICAN ADOLESCENT FEMALES; ACUTE MYOCARDIAL-INFARCTION; RECREATIONAL DRUG-USE; CHEST-WALL RIGIDITY; GERM-CELL TUMORS; CANNABIS USE; COCAINE USE; SPONGIFORM LEUKOENCEPHALOPATHY; MENINGOCOCCAL DISEASE AB Increasingly, the identification, assessment and treatment of unhealthy use of alcohol and other drugs often occur within general medical settings. Within this climate, there is a growing awareness of the physical effects connected to acute or chronic use of substances of abuse. By examining these associations and their purported biological causative mechanisms, greater clinical attention in the form of screening, identification and treatment - to co-occurring medical conditions as well as to the use of illicit substances itself may be possible. In this review, we examine recent peer-reviewed literature regarding three substances of abuse (cocaine, marijuana and opioids) and their direct associations with physical disorders. We group the association of diseases based on organ systems and critically examine the literature regarding the evidence to supporting those associations and causative mechanisms. There is good evidence to support the association of cocaine, marijuana and opioid use with a variety of physical health conditions. Unfortunately, while the causative evidence of these associations is preliminary, we could conclude that the use of these substances can incite a host of medical illnesses or complicate their treatment. When combined with societal, mental health and public health harms associated with the use of illicit substances, co-occurring or incident physical health conditions associated with substance use may present a substantial healthcare cost to the individual as well as to the healthcare system at large, resulting in a debilitating strain on often limited time and resources. (C) 2015 S. Karger AG, Basel C1 [Gordon, Adam J.; Conley, James W.] Univ Pittsburgh, Sch Med, CHERP, Pittsburgh, PA 15240 USA. [Gordon, Adam J.; Conley, James W.] Univ Pittsburgh, Sch Med, MIRECC, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15240 USA. [Gordon, Joanne M.] Missouri State Univ, Biomed Sci, Springfield, MO USA. RP Gordon, AJ (reprint author), Univ Pittsburgh, Sch Med, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, CHERP 151-C,Univ Dr C, Pittsburgh, PA 15240 USA. EM gordona@medschool.pitt.edu NR 122 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1662-4874 BN 978-3-318-02604-7; 978-3-318-02603-0 J9 KEY ISSUES MENT HEAL JI Key Iss. Ment. Health PY 2015 VL 179 BP 114 EP 128 DI 10.1159/000365543 PG 15 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA BG3GT UT WOS:000387942800013 ER PT J AU Penn, JL Martindale, JL Milne, LW Marill, KA AF Penn, Joshua L. Martindale, Jennfier L. Milne, Leslie W. Marill, Keith A. TI Aortic dissection associated with blunt chest trauma diagnosed by elevated D-dimer SO INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS LA English DT Article DE Aortic dissection; Chest trauma; D-dimer; Bovine-type aortic arch ID INTERNATIONAL REGISTRY; INJURY; DISEASE; IRAD; ARCH AB INTRODUCTION: Similar to spontaneous aortic dissection, traumatic aortic dissection is diagnosed with a careful history and physical exam, chest radiograph, and ultimately, dedicated aortic imaging. The diagnosis of spontaneous aortic dissection may be aided by using the serum D-dimer test. The use of D-dimer for diagnosing aortic injury in the setting of blunt trauma has not previously been reported. PRESENTATION OF CASE: We present a case of aortic dissection in a 61-year-old male diagnosed when the patient presented with chest pain after blunt chest trauma. DISCUSSION: The patient had no known history or risk factors for aortic disease. None of the classic findings were present by history, physical examination or chest radiograph and the diagnosis was made as the result of an elevated D-dimer. We discuss how the D-dimer test fortuitously led to the diagnosis in this case, and the implications. CONCLUSION: D-dimer could be helpful in diagnosing aortic injuries in low-risk chest trauma patients. (C) 2015 The Authors. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd. C1 [Penn, Joshua L.; Martindale, Jennfier L.] Harvard Med Sch, Dept Emergency Med, Harvard Affiliated Emergency Med Residency, Boston, MA 02115 USA. [Milne, Leslie W.; Marill, Keith A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Marill, KA (reprint author), 3600 Forbes Ave,Suite 400A, Pittsburgh, PA 15261 USA. EM kmarill@mgh.harvard.edu FU NHLBI NIH HHS [K12 HL109068] NR 21 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2210-2612 J9 INT J SURG CASE REP JI Int. J. Surg. Case Rep. PY 2015 VL 10 BP 76 EP 79 DI 10.1016/j.ijscr.2015.03.027 PG 4 WC Surgery SC Surgery GA ED3FL UT WOS:000388734800020 PM 25805614 ER PT S AU Otto, T AF Otto, Tobias BE Christiansen, H Christiansen, NM TI MYCN and Its Posttranslational Regulation in Neuroblastoma SO PROGRESSIVE NEUROBLASTOMA: INNOVATION AND NOVEL THERAPEUTIC STRATEGIES SE Pediatric and Adolescent Medicine LA English DT Article; Book Chapter ID SMALL-MOLECULE INHIBITORS; GROWTH IN-VITRO; N-MYC; AURORA KINASE; NEURONAL PRECURSORS; DIFFERENTIATION; PROTEIN; VIVO; PROLIFERATION; PROGRESSION AB High-risk neuroblastoma is frequently associated with amplification of the MYCN oncogene and this genetic aberration correlates strongly with poor prognosis in neuroblastoma patients. However, amplification of MYCN also offers new therapeutic opportunities since tumor cells that become addicted to high levels of N-Myc protein can be selectively targeted. In untransformed neuronal precursor cells, N-Myc is regulated by a series of posttranslational modifications that lead to its proteasomal degradation during mitosis. Neuroblastoma cells harboring amplification of MYCN, however, have developed mechanisms that impede the physiological degradation of N-Myc in order to sustain the high N-Myc activity required for proliferation and survival. Interference with this posttranslational regulation by pharmacologic inhibition of target proteins provides novel therapeutic approaches for neuroblastoma treatment. In this chapter, we will discuss the posttranslational regulation of N-Myc under physiological conditions as well as the mechanisms that MYCN-amplified neuroblastoma cells employ to evade this regulation. We will focus on the posttranslational regulation of N-Myc by PI3K/Akt signaling, Aurora-A, anaplastic lymphoma kinase and histone deacetylases. Furthermore, we will highlight to what extent this knowledge has been translated into new clinical treatment options. (C) 2015 S. Karger AG, Basel C1 [Otto, Tobias] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Otto, Tobias] Harvard Med Sch, Dept Genet, Boston, MA USA. RP Otto, T (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 28 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1017-5989 BN 978-3-318-05497-2; 978-3-318-05496-5 J9 PEDIATR ADOLESC MED JI Pediatr. Adolesc. Med. PY 2015 VL 20 BP 47 EP 58 DI 10.1159/000382085 D2 10.1159/isbn.978-3-318-05497-2 PG 12 WC Oncology; Pediatrics SC Oncology; Pediatrics GA BG2MZ UT WOS:000387487100006 ER PT S AU Yeung, CM George, RE AF Yeung, Caleb M. George, Rani E. BE Christiansen, H Christiansen, NM TI The Role of the Anaplastic Lymphoma Kinase Receptor in Neuroblastoma SO PROGRESSIVE NEUROBLASTOMA: INNOVATION AND NOVEL THERAPEUTIC STRATEGIES SE Pediatric and Adolescent Medicine LA English DT Article; Book Chapter ID ATP-COMPETITIVE INHIBITORS; NON-HODGKINS-LYMPHOMA; CELL LUNG-CANCER; TYROSINE KINASE; ALK KINASE; NPM-ALK; CRIZOTINIB RESISTANCE; ACTIVATING MUTATIONS; NERVOUS-SYSTEM; GROWTH-FACTOR AB Anaplastic lymphoma kinase (ALK) is a membrane-bound receptor tyrosine kinase that when aberrantly expressed is capable of promoting neuroblastoma pathogenesis, and serves as a bona fide therapeutic target. In this review, we discuss the physiologic role of ALK, the mechanisms and relationships of ALK signaling pathways, the role of mutant ALK, and its therapeutic targeting in neuroblastoma. (C) 2015 S. Karger AG, Basel C1 [Yeung, Caleb M.; George, Rani E.] Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Yeung, CM (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 93 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1017-5989 BN 978-3-318-05497-2; 978-3-318-05496-5 J9 PEDIATR ADOLESC MED JI Pediatr. Adolesc. Med. PY 2015 VL 20 BP 107 EP 120 DI 10.1159/000382093 D2 10.1159/isbn.978-3-318-05497-2 PG 14 WC Oncology; Pediatrics SC Oncology; Pediatrics GA BG2MZ UT WOS:000387487100010 ER PT B AU Manola, J Xu, W Giantonio, BJ AF Manola, Judith Xu, Wei Giantonio, Bruce J. BE OSullivan, B Brierley, JD DCruz, AK Fey, MF Pollock, R Vermorken, JB Huang, SH TI Assessment of treatment outcome SO UICC MANUAL OF CLINICAL ONCOLOGY, 9TH EDITION LA English DT Article; Book Chapter ID END-POINTS; RECOMMENDATIONS; TRIALS C1 [Manola, Judith] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Xu, Wei] Princess Margaret Canc Ctr, Dept Biostat, Toronto, ON, Canada. [Giantonio, Bruce J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Manola, J (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-119-01313-6; 978-1-4443-3244-5 PY 2015 BP 40 EP 52 D2 10.1002/9781119013143 PG 13 WC Oncology SC Oncology GA BG1BQ UT WOS:000386636800007 ER PT J AU Yonker, LM Zan, SY Scirica, CV Jethwani, K Kinane, TB AF Yonker, Lael M. Zan, Shiyi Scirica, Christina V. Jethwani, Kamal Kinane, T. Bernard TI "Friending" Teens: Systematic Review of Social Media in Adolescent and Young Adult Health Care SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Review DE social media; social networking sites; adolescents; young adults; health ID RANDOMIZED CONTROLLED-TRIAL; NETWORKING WEB SITE; COLLEGE-STUDENTS; SEXUAL HEALTH; MENTAL-HEALTH; LATINO ADOLESCENTS; FACEBOOK PROFILES; OLDER ADOLESCENTS; RISK BEHAVIOR; SUBSTANCE USE AB Background: Social media has emerged as a potentially powerful medium for communication with adolescents and young adults around their health choices. Objective: The goal of this systematic review is to identify research on the use of social media for interacting with adolescents and young adults in order to achieve positive health outcomes. Methods: A MEDLINE/PubMed electronic database search was performed between January 1, 2002 and October 1, 2013, using terms to identify peer-reviewed research in which social media and other Web 2.0 technologies were an important feature. We used a systematic approach to retrieve papers and extract relevant data. Results: We identified 288 studies involving social media, of which 87 met criteria for inclusion; 75 studies were purely observational and 12 were interventional. The ways in which social media was leveraged by these studies included (1) observing adolescent and young adult behavior (n= 77), (2) providing health information (n= 13), (3) engaging the adolescent and young adult community (n= 17), and (4) recruiting research participants (n= 23). Common health topics addressed included high-risk sexual behaviors (n= 23), alcohol, tobacco, and other drug use (n= 19), Internet safety (n= 8), mental health issues (n= 18), medical conditions (n= 11), or other specified issues (n= 12). Several studies used more than one social media platform and addressed more than one health-related topic. Conclusions: Social media technologies offer an exciting new means for engaging and communicating with adolescents and young adults; it has been successfully used to engage this age group, identify behaviors, and provide appropriate intervention and education. Nevertheless, the majority of studies to date have been preliminary and limited in their methodologies, and mostly center around evaluating how adolescents and young adults use social media and the resulting implications on their health. Although these explorations are essential, further exploration and development of these strategies into building effective interventions is necessary. C1 [Yonker, Lael M.; Scirica, Christina V.; Kinane, T. Bernard] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Yonker, Lael M.; Zan, Shiyi; Scirica, Christina V.; Jethwani, Kamal; Kinane, T. Bernard] Harvard Univ, Sch Med, Boston, MA USA. [Zan, Shiyi; Jethwani, Kamal] Partners Healthcare, Ctr Connected Hlth, Boston, MA USA. RP Kinane, TB (reprint author), Massachusetts Gen Hosp, Dept Pediat, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM tbkinane@partners.org NR 102 TC 22 Z9 22 U1 5 U2 17 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD JAN PY 2015 VL 17 IS 1 AR e4 DI 10.2196/jmir.3692 PG 15 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AY0YH UT WOS:000347320100005 PM 25560751 ER PT B AU Pfeiffer, CD Wong, B AF Pfeiffer, Christopher D. Wong, Brian BE Hospenthal, DR Rinaldi, MG TI Diagnostic Immunology SO DIAGNOSIS AND TREATMENT OF FUNGAL INFECTIONS, SECOND EDITION SE Infectious Disease-Series LA English DT Article; Book Chapter ID INVASIVE FUNGAL-INFECTIONS; BRONCHOALVEOLAR LAVAGE FLUID; LATEX-AGGLUTINATION-TEST; BETA-D-GLUCAN; GALACTOMANNAN ENZYME-IMMUNOASSAY; BLASTOMYCES-DERMATITIDIS ANTIGEN; CLINICAL-PRACTICE GUIDELINES; ORGAN TRANSPLANT RECIPIENTS; SERUM CRYPTOCOCCAL ANTIGEN; LINKED-IMMUNOSORBENT-ASSAY C1 [Pfeiffer, Christopher D.; Wong, Brian] Oregon Hlth & Sci Univ, Div Infect Dis, Dept Med, 3181 SW Sam Jackson Pk Rd,L457, Portland, OR 97239 USA. [Pfeiffer, Christopher D.] Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR 97239 USA. RP Wong, B (reprint author), Oregon Hlth & Sci Univ, Div Infect Dis, Dept Med, 3181 SW Sam Jackson Pk Rd,L457, Portland, OR 97239 USA. EM wongbri@ohsu.edu NR 96 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND BN 978-3-319-13090-3; 978-3-319-13089-7 J9 INFECT DIS-SER PY 2015 BP 45 EP 64 DI 10.1007/978-3-319-13090-3_5 D2 10.1007/978-3-319-13090-3 PG 20 WC Infectious Diseases SC Infectious Diseases GA BF9SL UT WOS:000385855800006 ER PT B AU Boucher, HW Patterson, TF AF Boucher, Helen W. Patterson, Thomas F. BE Hospenthal, DR Rinaldi, MG TI Aspergillosis SO DIAGNOSIS AND TREATMENT OF FUNGAL INFECTIONS, SECOND EDITION SE Infectious Disease-Series LA English DT Article; Book Chapter ID INVASIVE PULMONARY ASPERGILLOSIS; LIPOSOMAL AMPHOTERICIN-B; ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; CELL TRANSPLANT RECIPIENTS; POLYMERASE-CHAIN-REACTION; GUINEA-PIG MODEL; BETA-D-GLUCAN; FUNGAL-INFECTIONS; ANTIFUNGAL THERAPY; CONTROLLED-TRIAL C1 [Boucher, Helen W.] Tufts Med Ctr, Div Infect Dis & Geog Med, 800 Washington St,Box 238, Boston, MA 02111 USA. [Patterson, Thomas F.] Tufts Med Ctr, Div Infect Dis & Geog Med, 800 Washington St,Box 238, Boston, MA 02111 USA. Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Div, South Texas Vet Hlth Care Syst, Dept Med,Div Infect Dis, San Antonio, TX 78229 USA. EM hboucher@tuftsmedicalcenter.org NR 107 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND BN 978-3-319-13090-3; 978-3-319-13089-7 J9 INFECT DIS-SER PY 2015 BP 129 EP 140 DI 10.1007/978-3-319-13090-3_10 D2 10.1007/978-3-319-13090-3 PG 12 WC Infectious Diseases SC Infectious Diseases GA BF9SL UT WOS:000385855800011 ER PT S AU Raol, N Hartnick, CJ AF Raol, Nikhila Hartnick, Christopher J. BE Raol, N Hartnick, CJ TI Anatomy and Physiology of Velopharyngeal Closure and Insufficiency SO SURGERY FOR PEDIATRIC VELOPHARYNGEAL INSUFFICIENCY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID MUSCULUS UVULAE; CLEFT-PALATE; SPEECH; CHILDREN AB The velopharynx is a complex structure that is responsible for separation of the oral and nasal cavities during speech production and swallowing. Incompetence of this mechanism can lead to hypernasality, with nasal air emission and incomprehensible speech, as well as nasopharyngeal regurgitation. There can be a significant social stigma associated with velopharyngeal dysfunction, and surgical treatment can be curative in many cases. Knowledge of the normal anatomy and physiology of the velopharyngeal complex is essential when planning for surgical repair. (C) 2015 S. Karger AG, Basel C1 [Raol, Nikhila; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu NR 18 TC 0 Z9 0 U1 0 U2 5 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-318-02787-7; 978-3-318-02786-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2015 VL 76 BP 1 EP 6 DI 10.1159/000368003 D2 10.1159/isbn.978-3-318-02787-7 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA BG2CM UT WOS:000387250500002 PM 25733226 ER PT S AU Raol, N Hartnick, CJ AF Raol, Nikhila Hartnick, Christopher J. BE Raol, N Hartnick, CJ TI Surgery for Pediatric Velopharyngeal Insufficiency Preface SO SURGERY FOR PEDIATRIC VELOPHARYNGEAL INSUFFICIENCY SE Advances in Oto-Rhino-Laryngology LA English DT Editorial Material; Book Chapter C1 [Raol, Nikhila; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RP Raol, N (reprint author), Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-318-02787-7; 978-3-318-02786-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2015 VL 76 BP VI EP VI D2 10.1159/isbn.978-3-318-02787-7 PG 1 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA BG2CM UT WOS:000387250500001 ER PT S AU de Stadler, M Hersh, C AF de Stadler, Marie Hersh, Cheryl BE Raol, N Hartnick, CJ TI Nasometry, Videofluoroscopy, and the Speech Pathologist's Evaluation and Treatment SO SURGERY FOR PEDIATRIC VELOPHARYNGEAL INSUFFICIENCY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID VELOPHARYNGEAL GAP SIZE; CLEFT-PALATE; LANGUAGE ISSUES; INSUFFICIENCY; DYSFUNCTION; MANAGEMENT AB The speech-language pathologist (SLP) plays an important role in the assessment and management of children with velopharyngeal insufficiency (VPI). The SLP assesses speech sound production and oral nasal resonance and identifies the characteristics of nasal air emission to guide the clinical and surgical management of VPI. Clinical resonance evaluations typically include an oral motor exam, identification of nasal air emission, and analysis of the speech sound repertoire. Additional elements include perceptual assessment of intra-oral air pressure, the degree of hypernasality, and vocal loudness/quality. Clinical speech and resonance evaluations are typically the gold-standard evaluation method until a child reaches 3-4 years of age, when sufficient compliance levels and speech-language abilities allow for participation in instrumental testing. At that time, objective assessment measures are introduced, including nasometry, videofluoroscopy, and/or nasopharyngoscopy. Nasometry is a computer-based tool that quantifies nasal air escape and allows comparison of the score against normative data. Videofluoroscopy is a radiographic tool used to assess the shaping of the velum and closure of the velopharyngeal mechanism during speech production. Evaluation findings guide decision making regarding surgical candidacy and/or the therapeutic management of VPI. Surgery should always be pursued first when an anatomic deficit prevents velopharyngeal closure. Therapy should always be pursued in children who present with velopharyngeal mislearning and/or motor planning issues resulting in VPI. It is not uncommon for children to receive a combination of surgical intervention and speech resonance therapy during their VPI management course. Collaborative decision making between the otorhinolaryngologist and the SLP provides optimal patient care. (C) 2015 S. Karger AG, Basel C1 [de Stadler, Marie; Hersh, Cheryl] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, 275 Cambridge St,3rd Floor, Boston, MA 02114 USA. RP Hersh, C (reprint author), Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, 275 Cambridge St,3rd Floor, Boston, MA 02114 USA. EM cjhersh@partners.org NR 23 TC 0 Z9 0 U1 2 U2 6 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-318-02787-7; 978-3-318-02786-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2015 VL 76 BP 7 EP 17 DI 10.1159/000368004 D2 10.1159/isbn.978-3-318-02787-7 PG 11 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA BG2CM UT WOS:000387250500003 PM 25733227 ER PT S AU Raol, N Sagar, P Nimkin, K Hartnick, CJ AF Raol, Nikhila Sagar, Pallavi Nimkin, Katherine Hartnick, Christopher J. BE Raol, N Hartnick, CJ TI New Technology: Use of Cine MRI for Velopharyngeal Insufficiency SO SURGERY FOR PEDIATRIC VELOPHARYNGEAL INSUFFICIENCY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID VIDEOFLUOROSCOPY AB Cine magnetic resonance imaging (MRI) has been used since 1999 to evaluate velopharyngeal function. It allows the visualization of articulatory movement of the velopharyngeal port at rest and during speech. In addition, some studies have shown that it can be synched with audio and can define specific anatomic defects. Cine MRI also provides a non-invasive modality by which velopharyngeal closure can be evaluated. In this chapter, the utility and technique of cine MRI will be described. (C) 2015 S. Karger AG, Basel C1 [Raol, Nikhila; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Sagar, Pallavi; Nimkin, Katherine] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Raol, N (reprint author), Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM nikhila_raol@meei.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-318-02787-7; 978-3-318-02786-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2015 VL 76 BP 27 EP 32 DI 10.1159/000368011 D2 10.1159/isbn.978-3-318-02787-7 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA BG2CM UT WOS:000387250500005 PM 25733229 ER PT S AU Raol, N Hartnick, CJ AF Raol, Nikhila Hartnick, Christopher J. BE Raol, N Hartnick, CJ TI Superiorly Based Pharyngeal Flap SO SURGERY FOR PEDIATRIC VELOPHARYNGEAL INSUFFICIENCY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID VELOPHARYNGEAL INSUFFICIENCY; SURGERY; COMPLICATIONS; OUTCOMES; APNEA; IOWA AB First described in 1875 by Schoenborn as an inferiorly based flap, the pharyngeal flap is the most common surgical procedure performed for velopharyngeal insufficiency. Having undergone numerous modifications since its conception, the pharyngeal flap is now primarily designed as a superiorly based flap and is most effective for patients with good lateral wall motion but limited anteriorposterior motion due to poor palatal excursion. The primary aims of this chapter are to provide the clinician with indications for when to consider utilizing the superiorly based pharyngeal flap and to give a stepwise description of how to perform the procedure. (C) 2015 S. Karger AG, Basel C1 [Raol, Nikhila; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RP Raol, N (reprint author), Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM nikhila_raol@meei.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-318-02787-7; 978-3-318-02786-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2015 VL 76 BP 50 EP 57 DI 10.1159/000368016 D2 10.1159/isbn.978-3-318-02787-7 PG 8 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA BG2CM UT WOS:000387250500008 PM 25733232 ER PT S AU Raol, N Hartnick, CJ AF Raol, Nikhila Hartnick, Christopher J. BE Raol, N Hartnick, CJ TI Sphincter Pharyngoplasty SO SURGERY FOR PEDIATRIC VELOPHARYNGEAL INSUFFICIENCY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID VELOPHARYNGEAL INSUFFICIENCY; FURLOW PALATOPLASTY; MANAGEMENT; OUTCOMES; INCOMPETENCE; EXPERIENCE AB First described in 1950 by Hynes for patients with velopharyngeal insufficiency following cleft palate repair, the sphincter pharyngoplasty is a frequently used procedure for treating velopharyngeal insufficiency that rivals the pharyngeal flap in some centers as the most frequently used procedure. This technique is most effective for patients with good anterior-posterior motion but limited lateral wall motion. The primary aims of this chapter are to provide the clinician with indications for when to consider utilizing the sphincter pharyngoplasty and to give a stepwise description of how to perform the procedure. (C) 2015 S. Karger AG, Basel C1 [Raol, Nikhila; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RP Raol, N (reprint author), Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM nikhila_raol@meei.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-318-02787-7; 978-3-318-02786-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2015 VL 76 BP 58 EP 66 DI 10.1159/000368019 D2 10.1159/isbn.978-3-318-02787-7 PG 9 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA BG2CM UT WOS:000387250500009 PM 25733233 ER PT S AU Raol, N Hartnick, CJ AF Raol, Nikhila Hartnick, Christopher J. BE Raol, N Hartnick, CJ TI Furlow Double-Opposing Z-Plasty SO SURGERY FOR PEDIATRIC VELOPHARYNGEAL INSUFFICIENCY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID VELOPHARYNGEAL INSUFFICIENCY; PALATOPLASTY; MANAGEMENT AB First described in 1978 by Furlow for the repair of a cleft soft palate, the double-opposing z-plasty, also known as the Furlow palatoplasty, is an excellent procedure for repairing a submucous cleft. It is also useful in patients with touch closure who simply need lengthening of the soft palate and as an option for patients with anomalous carotid vasculature where pharyngeal flaps and sphincter pharyngoplasty are precarious. The primary aims of this chapter are to provide the clinician with indications for when to consider utilizing the Furlow palatoplasty and to give a stepwise description of how to perform the procedure. (C) 2015 S. Karger AG, Basel C1 [Raol, Nikhila; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RP Raol, N (reprint author), Massachusetts Eye & Ear Infirm, Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM nikhila_raol@meei.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-318-02787-7; 978-3-318-02786-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2015 VL 76 BP 67 EP 73 DI 10.1159/000368022 D2 10.1159/isbn.978-3-318-02787-7 PG 7 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA BG2CM UT WOS:000387250500010 PM 25733234 ER PT B AU Fecci, PE Chen, C Baumeister, S Dranoff, G AF Fecci, Peter E. Chen, Christina Baumeister, Susanne Dranoff, Glenn BE Bagnoli, F Rappuoli, R TI Cancer Immunotherapy: The Road to Rejection SO ADVANCED VACCINE RESEARCH: METHODS FOR THE DECADE OF VACCINES LA English DT Article; Book Chapter ID COLONY-STIMULATING FACTOR; CHIMERIC ANTIGEN RECEPTOR; RENAL-CELL CARCINOMA; RESISTANT PROSTATE-CANCER; TUMOR-INFILTRATING LYMPHOCYTES; PULSED DENDRITIC CELLS; METASTATIC MELANOMA PATIENTS; 1E10 ANTIIDIOTYPE VACCINE; EPITHELIAL OVARIAN-CANCER; DOSE-ESCALATION TRIAL AB Immunotherapy continues to gain both momentum and legitimacy as a rational mode of cancer therapy. The idea that the immune system, if correctly manipulated, might be capable of surveying, identifying, and eradicating, in precise fashion, those cells that have mutant or newly expressed proteins en route to neoplastic growth patterns has long proved intriguing. This idea has been gradually shaped into a variety of immunotherapy approaches ranging from antibodies to cell transfers to vaccines. A large number of tumour types are also under study, including melanoma, glioma, lung, prostate, breast, head/neck, cervical, ovarian, pancreas, renal cell, colorectal cancers, and lymphoma. This chapter will review the current state, applications, adjuncts, and challenges to the successful immune-based treatment of cancer, emphasizing clinical trials. C1 [Fecci, Peter E.; Chen, Christina] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Baumeister, Susanne] Harvard Med Sch, Boston Childrens Hosp, Dept Pediat, Boston, MA USA. [Baumeister, Susanne] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Dranoff, Glenn] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Fecci, PE (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. EM peter.fecci@duke.edu; cjackson@jhmi.edu; susanne.baumeister@childrens.harvard.edu; glenn_dranoff@dfci.harvard.edu NR 183 TC 0 Z9 0 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-910190-03-6 PY 2015 BP 359 EP 385 PG 27 WC Immunology SC Immunology GA BG3AR UT WOS:000387829400016 ER PT S AU Berenji, GR Li, YX Gonzalez-Odriozola, R Thenkondar, A AF Berenji, Gholam R. Li, Yuxin Gonzalez-Odriozola, Roberto Thenkondar, Anurada BE Preedy, VR TI Sodium Fluoride and PET Bone Scans SO FLUORINE: CHEMISTRY, ANALYSIS, FUNCTION AND EFFECTS SE Food and Nutritional Components in Focus LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; F-18-FLUORIDE PET; BREAST-CANCER; METABOLIC-ACTIVITY; SKELETAL KINETICS; PAGETS-DISEASE; ION; METASTASES; GRAFTS C1 [Berenji, Gholam R.; Li, Yuxin; Gonzalez-Odriozola, Roberto; Thenkondar, Anurada] VA Greater Los Angeles Healthcare Syst, Dept Nucl Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RP Berenji, GR (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Nucl Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Gholam.Berenji@va.gov NR 36 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 2045-1695 BN 978-1-78262-850-7; 978-1-84973-888-0 J9 FOOD NUTR COMPON FOC PY 2015 IS 6 BP 236 EP 254 D2 10.1039/9781782628507 PG 19 WC Chemistry, Analytical; Nutrition & Dietetics SC Chemistry; Nutrition & Dietetics GA BG3RW UT WOS:000388175200015 ER PT S AU Pfefferbaum, B Deshpande, SN Allen, SF Sherrieb, K AF Pfefferbaum, B. Deshpande, S. N. Allen, S. F. Sherrieb, K. BE Watson, RR Tabor, JA Ehiri, JE Preedy, VR TI Children's reactions and adjustment to natural disasters SO HANDBOOK OF PUBLIC HEALTH IN NATURAL DISASTERS: NUTRITION, FOOD, REMEDIATION AND PREPARATION SE Human Health Handbooks LA English DT Article; Book Chapter DE children; disaster; exposure; mental health; posttraumatic stress ID POSTTRAUMATIC-STRESS-DISORDER; HURRICANE KATRINA; MENTAL-HEALTH; NORWEGIAN CHILDREN; FOLLOW-UP; SRI-LANKA; ADOLESCENTS; TSUNAMI; TERRORISM; EXPOSURE AB This chapter reviews children's reactions to natural disasters and the factors which influence those reactions. Commonly-studied post-disaster outcomes in children include posttraumatic stress disorder, posttraumatic stress reactions, anxiety, depression, behavior problems, and substance use, and an emerging literature describes posttraumatic growth. In addition to exposure, a number of individual, family, and social factors influence children's reactions and recovery. Given that children have been identified as a vulnerable population in the context of disasters, systematic public health preparedness and response efforts as well as clinical services should address their special needs. C1 [Pfefferbaum, B.; Deshpande, S. N.; Allen, S. F.] Univ Oklahoma, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Terrorism & Disaster Ctr,Coll Med, POB 26901, Oklahoma City, OK 73126 USA. [Sherrieb, K.] Geisel Sch Med Dartmouth, Dept Psychiat, Lebanon, NH 03756 USA. [Sherrieb, K.] US Dept Vet Affairs, Natl Ctr PTSD, White River Jct, VT 05001 USA. RP Pfefferbaum, B (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Terrorism & Disaster Ctr,Coll Med, POB 26901, Oklahoma City, OK 73126 USA. EM betty-pfefferbaum@ouhsc.edu NR 42 TC 0 Z9 0 U1 1 U2 1 PU WAGENINGEN ACAD PUBL PI WAGENINGEN PA POSTBUS 220, 6700 AE WAGENINGEN, NETHERLANDS SN 2212-375X BN 978-90-8686-806-3; 978-90-8686-257-3 J9 HUM HEALT HANDB PY 2015 VL 10 BP 113 EP 124 DI 10.3920/978-90-8686-806-3_6 D2 10.3920/ 978-90-8686-806-3 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health; Nutrition & Dietetics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Nutrition & Dietetics GA BF9IH UT WOS:000385640500006 ER PT B AU Wong, KHK Truslow, JG Khankhel, AH Tien, J AF Wong, Keith H. K. Truslow, James G. Khankhel, Aimal H. Tien, Joe BE Brey, EM TI Biophysical Mechanisms That Govern the Vascularization of Microfluidic Scaffolds SO VASCULARIZATION: REGENERATIVE MEDICINE AND TISSUE ENGINEERING LA English DT Article; Book Chapter ID TUBES IN-VITRO; ENGINEERED TISSUES; ENDOTHELIAL-CELLS; DRAINAGE SYSTEMS; ANGIOGENESIS; MICROVESSELS; HYDROGELS; NETWORK; MODELS; MATRIX C1 [Wong, Keith H. K.; Truslow, James G.; Khankhel, Aimal H.; Tien, Joe] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Wong, Keith H. K.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA USA. RP Wong, KHK (reprint author), Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. NR 54 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-8046-6; 978-1-4665-8045-9 PY 2015 BP 109 EP 124 PG 16 WC Cell & Tissue Engineering SC Cell Biology GA BF9YF UT WOS:000386048400007 ER PT S AU Glass, K Quackenbush, J Kepner, J AF Glass, Kimberly Quackenbush, John Kepner, Jeremy GP IEEE TI High Performance Computing of Gene Regulatory Networks using a Message-Passing Model SO 2015 IEEE HIGH PERFORMANCE EXTREME COMPUTING CONFERENCE (HPEC) SE IEEE High Performance Extreme Computing Conference LA English DT Proceedings Paper CT IEEE High Performance Extreme Computing Conference (HPEC) CY SEP 15-17, 2015 CL Westin Hotel, MA ID INFERENCE AB Gene regulatory network reconstruction is a fundamental problem in computational biology. We recently developed an algorithm, called PANDA (Passing Attributes Between Networks for Data Assimilation), that integrates multiple sources of 'omics data and estimates regulatory network models. This approach was initially implemented in the C++ programming language and has since been applied to a number of biological systems. In our current research we are beginning to expand the algorithm to incorporate larger and most diverse datasets, to reconstruct networks that contain increasing numbers of elements, and to build not only single network models, but sets of networks. In order to accomplish these "Big Data" applications, it has become critical that we increase the computational efficiency of the PANDA implementation. In this paper we show how to recast PANDA's similarity equations as matrix operations. This allows us to implement a highly readable version of the algorithm using the MATLAB/Octave programming language. We find that the resulting M-code much shorter (103 compared to 1128 lines) and more easily modifiable for potential future applications. The new implementation also runs significantly faster, with increasing efficiency as the network models increase in size. Tests comparing the C-code and M-code versions of PANDA demonstrate that this speed-up is on the order of 20-80 times faster for networks of similar dimensions to those we find in current biological applications. C1 [Glass, Kimberly] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Glass, Kimberly] Harvard Med Sch, Boston, MA USA. [Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Quackenbush, John] Harvard Sch Publ Hlth, Boston, MA USA. [Kepner, Jeremy] Lincoln Lab, Cambridge, MA USA. [Kepner, Jeremy] MIT, Cambridge, MA 02139 USA. RP Glass, K (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM rekrg@channing.harvard.edu; johnq@jimmy.harvard.edu; kepner@ll.mit.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2377-6943 BN 978-1-4673-9286-0 J9 IEEE HIGH PERF EXTR PY 2015 PG 6 WC Computer Science, Hardware & Architecture; Computer Science, Theory & Methods SC Computer Science GA BF3HH UT WOS:000380543000039 ER PT J AU Athalye, P Sekeljic, NJ Ilic, MM Tonyushkin, AA Notaros, BM AF Athalye, Pranav Sekeljic, Nada J. Ilic, Milan M. Tonyushkin, Alexey A. Notaros, Branislav M. GP IEEE TI Improving Traveling-Wave RF Fields inside Magnetic Resonance Imaging Bores by Incorporating Dielectric Loadings SO 2015 USNC-URSI RADIO SCIENCE MEETING (JOINT WITH AP-S SYMPOSIUM) PROCEEDINGS LA English DT Meeting Abstract CT USNC-URSI Radio Science Meeting (Joint with AP-S Symposium) Proceedings CY JUL 19-19, 2015 CL Vancouver, CANADA SP Inst Elect Elect Engineers, IEEE Antennas Propagat Soc, IEEE, URSI C1 [Athalye, Pranav; Sekeljic, Nada J.; Ilic, Milan M.; Notaros, Branislav M.] Colorado State Univ, Elect & Comp Engn Dept, Ft Collins, CO 80523 USA. [Ilic, Milan M.] Univ Belgrade, Sch Elect Engn, Belgrade 11001, Serbia. [Tonyushkin, Alexey A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. EM athalye@rams.colostate.edu; inadasek@engr.colostate.edu; milanilic@etf.rs; atonyushkin@mgh.harvard.edu; notaros@colostate.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-7817-5 PY 2015 BP 316 EP 316 PG 1 WC Computer Science, Theory & Methods SC Computer Science GA BF3TC UT WOS:000380575300316 ER PT B AU Pal, C Martin, S AF Pal, Chiranjib Martin, Sunil BE Adak, S Datta, R TI Role of T-cells in Leishmania Infection SO LEISHMANIA: CURRENT BIOLOGY AND CONTROL LA English DT Article; Book Chapter ID EXPERIMENTAL CUTANEOUS LEISHMANIASIS; MAJOR INFECTION; VISCERAL LEISHMANIASIS; DONOVANI INFECTION; TGF-BETA; IMMUNOLOGICAL REGULATION; AMAZONENSIS INFECTION; DERMAL LEISHMANIASIS; DENDRITIC CELLS; BALB/C MICE AB T-cells play a critical role in the immunoregulation of anti-leishmanial immune response. In leishmaniasis, Th1-related cytokine production seems to be crucial for host control of parasite burden and clinical cure. Visceral and diffuse cutaneous leishmaniasis are characterized by negative skin test for parasite antigens and failure to produce Th1 cytokines, whereas tegumentary leishmaniasis is characterized by a positive skin test and the ability of peripheral blood mononuclear cells (PBMCs) to produce IL-12 and IFN-gamma (Th1 cytokine). In fact, IL-4 and IL-13 (Th2 cytokines) promote disease progression in cutaneous leishmaniasis, whereas IL-4 seems to enhance protective type-1 responses in visceral leishmaniasis. Thus, immune response to intracellular parasites shifted from the Th1/Th2 paradigm of resistance/susceptibility to a more biologically relevant regulatory and counter-regulatory network of diverse T-cell subsets. Moreover, the presence of antigen-specific regulatory T-cell subsets may provide an environment that contributes to the balance between Th1 and Th2 cells. Finally, the involvement of CD8(+) T-cells has been described, but the modality of their role and function in this kind of infection has not been expanded so far. Recently discovered Th17, Th9 and Tfh subsets and related cytokines have been reported to perform diverse functions in the course of leishmaniasis as a whole. Leishmania is one of the first microbes credited to employ T-reg cells for immunoevasion. IL-10-producing Foxp3(+) and Foxp3-T-reg subtypes perpetuate immunosuppression whereas inflammatory CD8(+) T-cells counter the immunosuppression, forcing the parasite to metastasize. A detailed understanding of these immune-regulatory checkpoints may expose novel drug targets, which may help in developing therapies against diseases with similar molecular aetiology. C1 [Pal, Chiranjib] West Bengal State Univ, Dept Zool, Cellular Immunol & Expt Therapeut Lab, Barasat, W Bengal, India. [Martin, Sunil] Harvard Med Sch, Dana Farber Harvard Canc Ctr, Canc Immunol Programme, Boston, MA USA. RP Pal, C (reprint author), West Bengal State Univ, Dept Zool, Cellular Immunol & Expt Therapeut Lab, Barasat, W Bengal, India. EM cpcu.immunology@gmail.com; sunil_martin@dfci.harvard.edu NR 85 TC 0 Z9 0 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-908230-53-9; 978-1-908230-52-2 PY 2015 BP 147 EP 166 PG 20 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BF9CI UT WOS:000385432000010 ER PT S AU Bhere, D Shah, K AF Bhere, Deepak Shah, Khalid BE Fisher, PB Tew, KD TI Stem Cell-Based Therapies for Cancer SO ADVANCES IN CANCER RESEARCH, VOL 127 SE Advances in Cancer Research LA English DT Review; Book Chapter ID APOPTOSIS-INDUCING LIGAND; MESENCHYMAL PROGENITOR CELLS; EGF RECEPTOR TRANSACTIVATION; LUNG METASTASIS MODEL; BONE-MARROW; IN-VITRO; OVARIAN-CANCER; BRAIN-TUMORS; GENE-THERAPY; TARGETED-DELIVERY AB Stem cell-based therapeutic strategies have emerged as very attractive treatment options over the past decade. Stem cells are now being utilized as delivery vehicles especially in cancer therapy to deliver a number of targeted proteins and viruses. This chapter aims to shed light on numerous studies that have successfully employed these strategies to target various cancer types with a special emphasis on numerous aspects that are critical to the success of future stem cell-based therapies for cancer. C1 [Bhere, Deepak; Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02215 USA. RP Shah, K (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02215 USA. EM kshah@mgh.harvard.edu NR 143 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-802942-8; 978-0-12-802920-6 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2015 VL 127 BP 159 EP 189 DI 10.1016/bs.acr.2015.04.012 PG 31 WC Oncology SC Oncology GA BF8GF UT WOS:000385011400004 PM 26093900 ER PT S AU Mul, JD Stanford, KI Hirshman, MF Goodyear, LJ AF Mul, Joram D. Stanford, Kristin I. Hirshman, Michael F. Goodyear, Laurie J. BE Bouchard, C TI Exercise and Regulation of Carbohydrate Metabolism SO MOLECULAR AND CELLULAR REGULATION OF ADAPTATION TO EXERCISE SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID HUMAN SKELETAL-MUSCLE; ACTIVATED PROTEIN-KINASE; STIMULATED GLUCOSE-UPTAKE; LIFE-STYLE INTERVENTION; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; 160 KDA AS160; GLUT4 TRANSLOCATION; INSULIN SENSITIVITY; AKT SUBSTRATE; BIOCHEMICAL ADAPTATIONS AB Carbohydrates are the preferred substrate for contracting skeletal muscles during high-intensity exercise and are also readily utilized during moderate intensity exercise. This use of carbohydrates during physical activity likely played an important role during the survival of early Homo sapiens, and genes and traits regulating physical activity, carbohydrate metabolism, and energy storage have undoubtedly been selected throughout evolution. In contrast to the life of early H. sapiens, modern lifestyles are predominantly sedentary. As a result, intake of excessive amounts of carbohydrates due to the easy and continuous accessibility to modern high-energy food and drinks has not only become unnecessary but also led to metabolic diseases in the face of physical inactivity. A resulting metabolic disease is type 2 diabetes, a complex endocrine disorder characterized by abnormally high concentrations of circulating glucose. This disease now affects millions of people worldwide. Exercise has beneficial effects to help control impaired glucose homeostasis with metabolic disease, and is a well-established tool to prevent and combat type 2 diabetes. This chapter focuses on the effects of exercise on carbohydrate metabolism in skeletal muscle and systemic glucose homeostasis. We will also focus on the molecular mechanisms that mediate the effects of exercise to increase glucose uptake in skeletal muscle. It is now well established that there are different proximal signaling pathways that mediate the effects of exercise and insulin on glucose uptake, and these distinct mechanisms are consistent with the ability of exercise to increase glucose uptake in the face of insulin resistance in people with type 2 diabetes. Ongoing research in this area is aimed at defining the precise mechanism by which exercise increases glucose uptake and insulin sensitivity and the types of exercise necessary for these important health benefits. C1 [Mul, Joram D.; Stanford, Kristin I.; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Med Sch, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Goodyear, Laurie J.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Harvard Med Sch, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.; Goodyear, LJ (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu FU NIAMS NIH HHS [R01 AR042238, R01-AR42238]; NIDDK NIH HHS [K01 DK105109, 5P30 DK36836, K01-DK105109, P30 DK036836, R01 DK099511, R01 DK101043, R01-DK099511, R01-DK101043] NR 127 TC 2 Z9 2 U1 2 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-803992-2; 978-0-12-803991-5 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2015 VL 135 BP 17 EP 37 DI 10.1016/bs.pmbts.2015.07.020 PG 21 WC Biochemistry & Molecular Biology; Sport Sciences SC Biochemistry & Molecular Biology; Sport Sciences GA BF8GN UT WOS:000385015700003 PM 26477909 ER PT J AU Mumenthaler, SM Foo, J Choi, NC Heise, N Leder, K Agus, DB Pao, W Michor, F Mallick, P AF Mumenthaler, Shannon M. Foo, Jasmine Choi, Nathan C. Heise, Nicholas Leder, Kevin Agus, David B. Pao, William Michor, Franziska Mallick, Parag TI The Impact of Microenvironmental Heterogeneity on the Evolution of Drug Resistance in Cancer Cells SO CANCER INFORMATICS LA English DT Article DE cancer; microenvironment; evolutionary modeling; drug resistance ID LUNG-CANCER; TUMOR MICROENVIRONMENT; ACQUIRED-RESISTANCE; MATHEMATICAL-MODEL; BREAST-CANCER; ANTICANCER THERAPY; GENE AMPLIFICATION; COLORECTAL-CANCER; DOSING SCHEDULES; EGFR INHIBITORS AB Therapeutic resistance arises as a result of evolutionary processes driven by dynamic feedback between a heterogeneous cell population and environmental selective pressures. Previous studies have suggested that mutations conferring resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in non-small-cell lung cancer (NSCLC) cells lower the fitness of resistant cells relative to drug-sensitive cells in a drug-free environment. Here, we hypothesize that the local tumor microenvironment could influence the magnitude and directionality of the selective effect, both in the presence and absence of a drug. Using a combined experimental and computational approach, we developed a mathematical model of preexisting drug resistance describing multiple cellular compartments, each representing a specific tumor environmental niche. This model was parameterized using a novel experimental dataset derived from the HCC827 erlotinib-sensitive and -resistant NSCLC cell lines. We found that, in contrast to in the drug-free environment, resistant cells may hold a fitness advantage compared to parental cells in microenvironments deficient in oxygen and nutrients. We then utilized the model to predict the impact of drug and nutrient gradients on tumor composition and recurrence times, demonstrating that these endpoints are strongly dependent on the microenvironment. Our interdisciplinary approach provides a model system to quantitatively investigate the impact of microenvironmental effects on the evolutionary dynamics of tumor cells. C1 [Mumenthaler, Shannon M.; Choi, Nathan C.; Agus, David B.] Univ Southern Calif, Keck Sch Med, Ctr Appl Mol Med, Los Angeles, CA USA. [Foo, Jasmine; Heise, Nicholas] Univ Minnesota, Sch Math, Minneapolis, MN 55455 USA. [Leder, Kevin] Univ Minnesota, Dept Ind & Syst Engn, Minneapolis, MN USA. [Pao, William] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN USA. [Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Michor, Franziska] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Mallick, Parag] Stanford Univ, Dept Radiol, Canary Ctr Stanford Canc Early Detect, Palo Alto, CA 94304 USA. RP Foo, J (reprint author), Univ Minnesota, Sch Math, Minneapolis, MN 55455 USA. EM jyfoo@math.umn.edu; michor@jimmy.harvard.edu; paragm@stanford.edu FU NCI NIH HHS [P30 CA014089, U54 CA143798, U54 CA143907] NR 73 TC 7 Z9 8 U1 3 U2 5 PU LIBERTAS ACAD PI AUCKLAND PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND SN 1176-9351 J9 CANCER INFORM JI Cancer Inform. PY 2015 VL 14 SU 4 BP 19 EP 31 DI 10.4137/CIN.S19338 PG 13 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA DW9GW UT WOS:000383965600003 PM 26244007 ER PT J AU Taneli, T Guo, YH Mushtaq, S AF Taneli, Tolga Guo, Yu-Heng Mushtaq, Sabina BE Ascher, MS Levounis, P TI Internet Gaming Disorder Virtual or Real? SO BEHAVIORAL ADDICTIONS LA English DT Article; Book Chapter ID VIDEO GAMES; ADDICTION C1 [Taneli, Tolga; Mushtaq, Sabina] Rutgers New Jersey Med Sch, Div Child & Adolescent Psychiat, Dept Psychiat, New Brunswick, NJ 08903 USA. [Guo, Yu-Heng] Hosp Univ Penn, Dept Psychiat, Psychiat, Philadelphia, PA 19104 USA. [Guo, Yu-Heng] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Taneli, T (reprint author), Rutgers New Jersey Med Sch, Div Child & Adolescent Psychiat, Dept Psychiat, New Brunswick, NJ 08903 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA BN 978-1-58562-485-0 PY 2015 BP 67 EP 80 PG 14 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA BF6IT UT WOS:000383141300007 ER PT J AU Zaman, T Lache, D AF Zaman, Tauheed Lache, Daniel BE Ascher, MS Levounis, P TI Texting and E-mail Problem Use SO BEHAVIORAL ADDICTIONS LA English DT Article; Book Chapter ID MOBILE PHONE USE; YOUNG-ADULTS; INTERNET C1 [Zaman, Tauheed] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lache, Daniel] Univ Penn, Philadelphia VA Med Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Zaman, T (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 18 TC 1 Z9 1 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA BN 978-1-58562-485-0 PY 2015 BP 101 EP 112 PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA BF6IT UT WOS:000383141300009 ER PT J AU Beheshti, A Neuberg, D McDonald, JT Vanderburg, CR Evens, AM AF Beheshti, Afshin Neuberg, Donna McDonald, J. Tyson Vanderburg, Charles R. Evens, Andrew M. TI The Impact of Age and Sex in DLBCL: Systems Biology Analyses Identify Distinct Molecular Changes and Signaling Networks SO CANCER INFORMATICS LA English DT Article DE aging and cancer; non-Hodgkin lymphoma; tumor progression; JUN; sex and cancer; DLBCL; diffuse large B-cell lymphoma; TCGA ID B-CELL LYMPHOMA; NON-HODGKIN-LYMPHOMA; N-TERMINAL KINASES; EXPRESSION PROFILES; CANCER PROGRESSION; CYTOCHROME-C; INHIBITORS; SURVIVAL; PROGNOSIS; RITUXIMAB AB Potential molecular alterations based on age and sex are not well defined in diffuse large B-cell lymphoma (DLBCL). We examined global transcriptome DLBCL data from The Cancer Genome Atlas (TCGA) via a systems biology approach to determine the molecular differences associated with age and sex. Collectively, sex and age revealed striking transcriptional differences with older age associated with decreased metabolism and telomere functions and female sex was associated with decreased interferon signaling, transcription, cell cycle, and PD-1 signaling. We discovered that the key genes for most groups strongly regulated immune function activity. Furthermore, older females were predicted to have less DLBCL progression versus older males and young females. Finally, analyses in systems biology revealed that JUN and CYCS signaling were the most critical factors associated with tumor progression in older and male patients. We identified important molecular perturbations in DLBCL that were strongly associated with age and sex and were predicted to strongly influence tumor progression. C1 [Beheshti, Afshin] Tufts Med Ctr, Mol Oncol Res Inst, Div Hematol Oncol, Boston, MA USA. [Neuberg, Donna] Harvard Univ, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [McDonald, J. Tyson] Hampton Univ, Canc Res Ctr, Hampton, VA 23668 USA. [Vanderburg, Charles R.] Massachusetts Gen Hosp, Harvard NeuroDiscovery Ctr, Boston, MA 02114 USA. [Evens, Andrew M.] Tufts Med Ctr, Tufts Canc Ctr, Boston, MA 02111 USA. [Evens, Andrew M.] Tufts Med Ctr, Div Hematol Oncol, Boston, MA USA. [Evens, Andrew M.] Tufts Univ, Sch Med, Med, Boston, MA 02111 USA. RP Evens, AM (reprint author), Tufts Med Ctr, Tufts Canc Ctr, Boston, MA 02111 USA. EM AEvens@tuftsmedicalcenter.org OI Beheshti, Afshin/0000-0003-4643-531X FU NCI NIH HHS [R01 CA164311] NR 29 TC 3 Z9 3 U1 0 U2 0 PU LIBERTAS ACAD PI AUCKLAND PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND SN 1176-9351 J9 CANCER INFORM JI Cancer Inform. PY 2015 VL 14 BP 141 EP 148 DI 10.4137/CIN.S34144 PG 8 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA DW9ET UT WOS:000383959500001 PM 26691437 ER PT J AU Mazzola, E Blackford, A Parmigiani, G Biswas, S AF Mazzola, Emanuele Blackford, Amanda Parmigiani, Giovanni Biswas, Swati TI Recent Enhancements to the Genetic Risk Prediction Model BRCAPRO SO CANCER INFORMATICS LA English DT Article DE BRCAPRO; BRCA1; BRCA2; mutation carrier; breast cancer; ovarian cancer ID BREAST-CANCER; CARRIER PROBABILITIES; MUTATION CARRIERS AB BRCAPRO is a widely used model for genetic risk prediction of breast cancer. It is a function within the R package BayesMendel and is used to calculate the probabilities of being a carrier of a deleterious mutation in one or both of the BRCA genes, as well as the probability of being affected with breast and ovarian cancer within a defined time window. Both predictions are based on information contained in the counselee's family history of cancer. During the last decade, BRCAPRO has undergone several rounds of successive refinements: the current version is part of release 2.1 of BayesMendel. In this review, we showcase some of the most notable features of the software resulting from these recent changes. We provide examples highlighting each feature, using artificial pedigrees motivated by complex clinical examples. We illustrate how BRCAPRO is a comprehensive software for genetic risk prediction with many useful features that allow users the flexibility to incorporate varying amounts of available information. C1 [Mazzola, Emanuele; Parmigiani, Giovanni] Harvard TH Chan Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mazzola, Emanuele; Parmigiani, Giovanni] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Blackford, Amanda] Johns Hopkins Univ, Sch Med, Div Biostat & Bioinformat, Baltimore, MD USA. [Biswas, Swati] Univ Texas Dallas, Dept Math Sci, Richardson, TX 75083 USA. RP Mazzola, E (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM mazzola@jimmy.harvard.edu FU NCI NIH HHS [P30 CA006516, R03 CA173834] NR 14 TC 3 Z9 3 U1 0 U2 0 PU LIBERTAS ACAD PI AUCKLAND PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND SN 1176-9351 J9 CANCER INFORM JI Cancer Inform. PY 2015 VL 14 SU 2 BP 147 EP 157 DI 10.4137/CIN.S17292 PG 11 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA DW9FH UT WOS:000383960900015 PM 25983549 ER PT S AU Xie, ZY Zhu, AJ Chen, LG McCarthy, T AF Xie, Zhiyong Zhu, Aijun Chen, Laigao McCarthy, Timothy BE Gao, F Shi, K Li, S TI Region-Based Data-Driven Intensity Normalization for Group Comparison of Functional Brain Images SO COMPUTATIONAL METHODS FOR MOLECULAR IMAGING SE Lecture Notes in Computational Vision and Biomechanics LA English DT Article; Book Chapter DE Brain imaging; Glucose metabolism; Intensity normalization; PET; SPECT AB Intensity normalization is widely used to remove the confounding effect of global change exhibited in PET or SPECT brain images such that the local activity can be detected. Improper estimate of global change may induce a biased normalization. To separate the global change from local measurements, an iterative method is proposed to identify reference regions that are not affected by the local activity. From more than one hundred predefined anatomical regions, the reference regions are selected based on their intensity similarity between two groups. Weighted least squares regression is used to compute linear intensity transformations to align intensities of corresponding reference regions across all subjects. Studies with simulated data demonstrated that the proposed method performed better in recovering real intensity change comparing with global mean normalization and with Andersson's data-driven method. C1 [Xie, Zhiyong; Chen, Laigao; McCarthy, Timothy] Pfizer Inc, Cambridge, MA 02139 USA. [Zhu, Aijun] Massachusetts Gen Hosp, Cambridge, MA USA. RP Xie, ZY (reprint author), Pfizer Inc, Cambridge, MA 02139 USA. EM Zhiyong.Xie@pfizer.com NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2212-9391 BN 978-3-319-18431-9; 978-3-319-18430-2 J9 L N COMPUT VIS BIOME PY 2015 VL 22 BP 113 EP 122 DI 10.1007/978-3-319-18431-9_12 D2 10.1007/978-3-319-18431-9 PG 10 WC Biophysics; Computer Science, Artificial Intelligence; Engineering, Biomedical SC Biophysics; Computer Science; Engineering GA BF6NS UT WOS:000383355200012 ER PT B AU Caplan, D AF Caplan, David BE Hillis, AE TI THE NEURAL BASIS OF SYNTACTIC PROCESSING A Critical Review SO HANDBOOK OF ADULT LANGUAGE DISORDERS, 2ND EDITION LA English DT Review; Book Chapter ID EVENT-RELATED POTENTIALS; REAL-TIME COMPREHENSION; SENTENCE COMPREHENSION; BRAIN POTENTIALS; WORKING-MEMORY; LANGUAGE COMPREHENSION; AMBIGUITY RESOLUTION; AGRAMMATIC APHASIA; LEFT-HEMISPHERE; POSITIVE SHIFT C1 [Caplan, David] Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. NR 118 TC 0 Z9 0 U1 2 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH ROAD, HOVE BN3 2FA, E SUSSEX, ENGLAND BN 978-1-84872-686-4; 978-1-315-71355-7; 978-1-84872-685-7 PY 2015 BP 355 EP 374 PG 20 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA BF6IY UT WOS:000383145600019 ER PT J AU Ratzliff, AH Unutzer, J Pascualy, M AF Ratzliff, Anna H. Unutzer, Jurgen Pascualy, Marcella BE Raney, LE TI Training Psychiatrists for Integrated Care SO INTEGRATED CARE: WORKING AT THE INTERFACE OF PRIMARY CARE AND BEHAVIORAL HEALTH LA English DT Article; Book Chapter ID PRIMARY MEDICAL-CARE; MENTAL-HEALTH-CARE; COLLABORATIVE CARE; INTERPROFESSIONAL EDUCATION; RESIDENTS; DEPRESSION; SETTINGS; ILLNESS; SERVICES; PROGRAMS C1 [Ratzliff, Anna H.; Unutzer, Jurgen] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Unutzer, Jurgen] Univ Washington, Hlth Serv & Global Hlth, Seattle, WA 98195 USA. [Unutzer, Jurgen] Univ Washington, Div Integrated Care & Publ Hlth, Seattle, WA 98195 USA. [Unutzer, Jurgen] Univ Washington, AIMS Adv Integrated Mental Hlth Solut Ctr, Seattle, WA 98195 USA. [Pascualy, Marcella] VA Puget Sound Hlth Care Syst, Psychiat & Behav Sci, Seattle, WA USA. RP Ratzliff, AH (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 33 TC 1 Z9 1 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA BN 978-1-58562-480-5 PY 2015 BP 113 EP 138 PG 26 WC Health Care Sciences & Services; Health Policy & Services; Primary Health Care; Psychiatry SC Health Care Sciences & Services; General & Internal Medicine; Psychiatry GA BF6IR UT WOS:000383139600008 ER PT J AU Vaillant, GE AF Vaillant, George E. BE Jeste, DV Palmer, BW TI Resilience and Posttraumatic Growth SO POSITIVE PSYCHIATRY: A CLINICAL HANDBOOK LA English DT Article; Book Chapter ID POSITIVE EMOTIONS; LIFE C1 [Vaillant, George E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Vaillant, GE (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. NR 39 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA BN 978-1-58562-495-9 PY 2015 BP 45 EP 70 D2 10.1176/appi.books.9781615370818 PG 26 WC Psychiatry SC Psychiatry GA BF6IU UT WOS:000383142600004 ER PT J AU Parks, AC Kleiman, EM Kashdan, TB Hausmann, LRM Meyer, PS Day, AM Spillane, NS Kahler, CW AF Parks, Acacia C. Kleiman, Evan M. Kashdan, Todd B. Hausmann, Leslie R. M. Meyer, Piper S. Day, Anne M. Spillane, Nichea S. Kahler, Christopher W. BE Jeste, DV Palmer, BW TI Positive Psychotherapeutic and Behavioral Interventions SO POSITIVE PSYCHIATRY: A CLINICAL HANDBOOK LA English DT Article; Book Chapter ID SMOKING-CESSATION TREATMENT; DEPRESSIVE SYMPTOMS; MAJOR DEPRESSION; METAANALYSIS; HAPPINESS; LIFE; SCHIZOPHRENIA; FEASIBILITY; EXPERIENCE; GRATITUDE C1 [Parks, Acacia C.] Hiram Coll, Psychol, Hiram, OH 44234 USA. [Kleiman, Evan M.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Kashdan, Todd B.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Kashdan, Todd B.] George Mason Univ, Ctr Consciousness & Transformat, Fairfax, VA 22030 USA. [Hausmann, Leslie R. M.] VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA USA. [Hausmann, Leslie R. M.] Univ Pittsburgh, Sch Med, Med, Pittsburgh, PA USA. [Meyer, Piper S.] Univ Minnesota, Minnesota Ctr Mental Hlth, St Paul, MN 55108 USA. [Day, Anne M.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Spillane, Nichea S.] Brown Univ, Ctr Alcohol & Addict Studies, Res, Providence, RI 02912 USA. [Kahler, Christopher W.] Brown Univ, Dept Behav & Social Sci, Providence, RI 02912 USA. RP Parks, AC (reprint author), Hiram Coll, Psychol, Hiram, OH 44234 USA. NR 37 TC 1 Z9 1 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA BN 978-1-58562-495-9 PY 2015 BP 147 EP 165 D2 10.1176/appi.books.9781615370818 PG 19 WC Psychiatry SC Psychiatry GA BF6IU UT WOS:000383142600009 ER PT J AU Olsen, LR Simon, C Kudahl, UJ Bagger, FO Winther, O Reinherz, EL Zhang, GL Brusic, V AF Olsen, Lars R. Simon, Christian Kudahl, Ulrich J. Bagger, Frederik O. Winther, Ole Reinherz, Ellis L. Zhang, Guang L. Brusic, Vladimir TI A computational method for identification of vaccine targets from protein regions of conserved human leukocyte antigen binding SO BMC MEDICAL GENOMICS LA English DT Article; Proceedings Paper CT Joint 26th Genome Informatics Workshop / Asia-Pacific-Bioinformatics-Network (APBioNet) 14th International Conference on Bioinformatics (GIW/InCoB) CY SEP 09-11, 2015 CL Tokyo, JAPAN SP Asia Pacific Bioinformat Network ID MULTIPLE SEQUENCE ALIGNMENT; CD8(+) T-CELLS; PROTECTIVE IMMUNITY; PREDICTION SERVERS; HIV VACCINE; PEPTIDE; DIVERSITY; EPITOPES; DESIGN; RESPONSES AB Background: Computational methods for T cell-based vaccine target discovery focus on selection of highly conserved peptides identified across pathogen variants, followed by prediction of their binding of human leukocyte antigen molecules. However, experimental studies have shown that T cells often target diverse regions in highly variable viral pathogens and this diversity may need to be addressed through redefinition of suitable peptide targets. Methods: We have developed a method for antigen assessment and target selection for polyvalent vaccines, with which we identified immune epitopes from variable regions, where all variants bind HLA. These regions, although variable, can thus be considered stable in terms of HLA binding and represent valuable vaccine targets. Results: We applied this method to predict CD8(+) T-cell targets in influenza A H7N9 hemagglutinin and significantly increased the number of potential vaccine targets compared to the number of targets discovered using the traditional approach where low-frequency peptides are excluded. Conclusions: We developed a webserver with an intuitive visualization scheme for summarizing the T cell-based antigenic potential of any given protein or proteome using human leukocyte antigen binding predictions and made a web-accessible software implementation freely available at http://met-hilab.cbs.dtu.dk/blockcons/. C1 [Olsen, Lars R.; Simon, Christian; Kudahl, Ulrich J.; Reinherz, Ellis L.; Zhang, Guang L.; Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Olsen, Lars R.; Bagger, Frederik O.; Winther, Ole] Univ Copenhagen, Dept Biol, Bioinformat Ctr, Copenhagen, Denmark. [Olsen, Lars R.; Simon, Christian; Kudahl, Ulrich J.] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, Lyngby, Denmark. [Bagger, Frederik O.] Univ Copenhagen, BRIC, Copenhagen, Denmark. [Simon, Christian] Univ Copenhagen, Novo Nordisk Ctr Prot Res, Dis Syst Biol, Copenhagen, Denmark. [Bagger, Frederik O.] Univ Copenhagen, Fac Hlth Sci, Rigshosp, Finsen Lab, Copenhagen, Denmark. [Reinherz, Ellis L.] Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. [Reinherz, Ellis L.] Harvard Med Sch, Dept Med, Boston, MA USA. [Zhang, Guang L.] Boston Univ, Metropolitan Coll, Dept Comp Sci, Boston, MA 02215 USA. [Brusic, Vladimir] Nazarbayev Univ, Sch Med, Astana, Kazakhstan. [Brusic, Vladimir] Nazarbayev Univ, Bioinformat Ctr, Astana, Kazakhstan. RP Brusic, V (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. EM vladimir.brusic@nu.edu.kz OI Simon, Christian/0000-0002-5866-5967; Otzen Bagger, Frederik/0000-0003-0636-8845 FU NIAID NIH HHS [U01 AI 90043] NR 39 TC 1 Z9 1 U1 0 U2 0 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 PY 2015 VL 8 SU 4 AR S1 DI 10.1186/1755-8794-8-S4-S1 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA DV5VK UT WOS:000382998600001 PM 26679766 ER PT J AU Sun, J Brusic, V AF Sun, Jing Brusic, Vladimir TI A systematic analysis of a broadly neutralizing antibody AR3C epitopes on Hepatitis C virus E2 envelope glycoprotein and their cross-reactivity SO BMC MEDICAL GENOMICS LA English DT Article; Proceedings Paper CT Joint 26th Genome Informatics Workshop / Asia-Pacific-Bioinformatics-Network (APBioNet) 14th International Conference on Bioinformatics (GIW/InCoB) CY SEP 09-11, 2015 CL Tokyo, JAPAN SP Asia Pacific Bioinformat Network ID MONOCLONAL-ANTIBODIES; VIRAL-HEPATITIS; INFECTION; DATABASE AB Background: Hepatitis C virus (HCV) belongs to Flaviviridae family of viruses. HCV represents a major challenge to public health since its estimated global prevalence is 2.8% of the world's human population. The design and development of HCV vaccine has been hampered by rapid evolution of viral quasispecies resulting in antibody escape variants. HCV envelope glycoprotein E1 and E2 that mediate fusion and entry of the virus into host cells are primary targets of the host immune responses. Results: Structural characterization of E2 core protein and a broadly neutralizing antibody AR3C together with E1E2 sequence information enabled the analysis of B-cell epitope variability. The E2 binding site by AR3C and its surrounding area were identified from the crystal structure of E2c-AR3C complex. We clustered HCV strains using the concept of "discontinuous motif/peptide" and classified B-cell epitopes based on their similarity. Conclusions: The assessment of antibody neutralizing coverage provides insights into potential cross-reactivity of the AR3C neutralizing antibody across a large number of HCV variants. C1 [Sun, Jing] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. [Brusic, Vladimir] Nazarbayev Univ, Sch Med, Astana, Kazakhstan. [Brusic, Vladimir] Nazarbayev Univ, Bioinformat Ctr, Astana, Kazakhstan. RP Sun, J (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. EM jing_sun@dfci.harvard.edu NR 34 TC 1 Z9 1 U1 0 U2 0 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 PY 2015 VL 8 SU 4 AR S6 DI 10.1186/1755-8794-8-S4-S6 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA DV5VK UT WOS:000382998600006 PM 26681161 ER PT S AU Unkelbach, J AF Unkelbach, J. BE Jaffray, DA TI Non-uniform spatiotemporal fractionation schemes in photon radiotherapy SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2 SE IFMBE Proceedings LA English DT Proceedings Paper CT World Congress on Medical Physics and Biomedical Engineering CY JUN 07-12, 2015 CL Toronto, CANADA DE Radiotherapy; Fractionation; BED AB Fractionation decisions in radiotherapy face the tradeoff between increasing the number of fractions to spare normal tissues, and increasing the total dose to achieve the same level of tumor control. In that regard, the ideal treatment would fractionate in normal tissues while simultaneously hypofractionating in the tumor. Interestingly, this is possible to a limited degree by delivering distinct dose distributions in different fractions. The dose distributions have to be designed such that similar doses are delivered to normal tissues while delivering high single fraction doses to parts of the tumor. In this paper, proof-of-concept is provided that this concept may lead to an improved therapeutic ratio for rotation therapy treatments using conventional photon beams. An idealized model of a large tumor treated in two fractions is considered. Fractionation effects are modeled via the biologically equivalent dose model. It is shown that the optimal treatment delivers the dose to the center of the tumor in a single fraction, while the second fraction delivers dose only to the rim of the tumor. The approach may potentially be interesting for large tumors embedded in a dose-limiting organ treated with stereotactic regimens. C1 [Unkelbach, J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Unkelbach, J (reprint author), Massachusetts Gen Hosp, 30 Fruit St, Boston, MA 02114 USA. EM junkelbach@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1680-0737 BN 978-3-319-19387-8; 978-3-319-19386-1 J9 IFMBE PROC PY 2015 VL 51 BP 401 EP 404 DI 10.1007/978-3-319-19387-8_97 PG 4 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BF5AQ UT WOS:000381813000097 ER PT S AU Bangert, M Unkelbach, J AF Bangert, M. Unkelbach, J. BE Jaffray, DA TI Objective function surrogates for iterative beam angle selection SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2 SE IFMBE Proceedings LA English DT Proceedings Paper CT World Congress on Medical Physics and Biomedical Engineering CY JUN 07-12, 2015 CL Toronto, CANADA DE Radiation therapy; IMRT; treatment planning; beam angle selection/optimization ID MODULATED RADIATION-THERAPY; OPTIMIZATION AB Optimized non-coplanar beam ensembles may yield substantial improvements of radiation therapy treatment plan quality. However, beam angle selection (BAS) is a non-trivial process and automated beam ensemble optimization is not supported by most commercial treatment planning systems, in part due to the lack of efficient algorithms. We focus on iterative BAS, where a beam ensemble is sequentially constructed: the basis for BAS during iteration n is a treatment plan containing n-1 fixed beams. To select the nth beam, each remaining candidate beam is added one-by-one to the current beam ensemble and the fluence map optimization (FMO) problem is solved. The beam yielding the lowest objective function value is selected. In this work we investigate two alternative methods relying on objective function surrogates to score candidate beams in order to make iterative BAS computationally more efficient: Conventional iterative BAS is compared to (1) an approach where the FMO is not solved to optimality but stopped after five iterations of a gradient based algorithm and (2) an approach where candidate beams are scored based on a projected gradient of the FMO in the first iteration. In a treatment planning study including one pancreas, one prostate, and one intracranial case, it is observed that both iterative BAS methods using objective function surrogates yield similar plan quality compared to naive iterative BAS with regard to the resulting the objective function values and DVHs. At the same time, the surrogates enable reductions in computation time by a factor of 50-100 making them highly attractive for clinical application. C1 [Bangert, M.] German Canc Res Ctr, Dept Med Phys Radiat Oncol, Heidelberg, Germany. [Unkelbach, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Unkelbach, J.] Harvard Med Sch, Dept Radiat Oncol, Boston, MA USA. RP Bangert, M (reprint author), German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM m.bangert@dkfz.de NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1680-0737 BN 978-3-319-19387-8; 978-3-319-19386-1 J9 IFMBE PROC PY 2015 VL 51 BP 413 EP 416 DI 10.1007/978-3-319-19387-8_100 PG 4 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BF5AQ UT WOS:000381813000100 ER PT S AU Jermoumi, M Yucel, A Hao, Y Cifter, G Sajo, E Ngwa, W AF Jermoumi, M. Yucel, A. Hao, Y. Cifter, G. Sajo, E. Ngwa, W. BE Jaffray, DA TI A Software App for Radiotherapy with In-situ Dose-painting using high Z nanoparticles SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2 SE IFMBE Proceedings LA English DT Proceedings Paper CT World Congress on Medical Physics and Biomedical Engineering CY JUN 07-12, 2015 CL Toronto, CANADA DE Dose painting; dose enhancement; high atomic number nanoparticles ID GOLD NANOPARTICLES; RADIATION-THERAPY; BRACHYTHERAPY; ENHANCEMENT; IRRADIATION; AGENTS AB The purpose of this work is to develop a user friendly and free-to-download application software that can be employed for modeling Radiotherapy with In-situ Dose-painting (RAID) using high-Z nanoparticles (HZNPs). The RAID APP is software program written in Matlab (Mathworks, Natick, MA, USA) based on deterministic code developed to simulate the space-time intra-tumor HZNPs biodistribution within the tumor, and the corresponding dose enhancement in response to low dose rate (LDR) brachytherapy of I-125, Pd-102, Cs-131 and kilovoltage x-rays such as 50 keV and 100 keV. Through the graphical user interface (GUI) of the RAID APP, the user will be directed to different features to compute various parameters related to the dose enhancement and the biodistribution of NPs within high risk tumor sub-volumes. The software was developed as a tool for research purposes with potential for subsequent development to guide dose-painting treatment planning using radiosensitizers such as gold (Au) and platinum (Pt). C1 [Jermoumi, M.; Yucel, A.; Hao, Y.; Cifter, G.; Sajo, E.; Ngwa, W.] Univ Massachusetts Lowell, Med Phys Program, Dept Phys & Appl Phys, Lowell, MA 01852 USA. [Jermoumi, M.; Cifter, G.; Ngwa, W.] Dana Farber Canc Inst, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Jermoumi, M.; Cifter, G.; Ngwa, W.] Harvard Med Sch, Boston, MA USA. RP Jermoumi, M (reprint author), Univ Massachusetts Lowell, Med Phys Program, Dept Phys & Appl Phys, Lowell, MA 01852 USA. FU NCI NIH HHS [K01 CA172478] NR 12 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1680-0737 BN 978-3-319-19387-8; 978-3-319-19386-1 J9 IFMBE PROC PY 2015 VL 51 BP 618 EP 621 DI 10.1007/978-3-319-19387-8_151 PG 4 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BF5AQ UT WOS:000381813000151 PM 27453711 ER PT S AU Pinter, C Lasso, A Wang, A Sharp, GC Alexander, K Jaffray, D Fichtinger, G AF Pinter, Csaba Lasso, Andras Wang, An Sharp, Gregory C. Alexander, Kevin Jaffray, David Fichtinger, Gabor BE Jaffray, DA TI Performing radiation therapy research using the open-source SlicerRT toolkit SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2 SE IFMBE Proceedings LA English DT Proceedings Paper CT World Congress on Medical Physics and Biomedical Engineering CY JUN 07-12, 2015 CL Toronto, CANADA DE Radiation therapy; 3D Slicer; DICOM-RT; dosimetry; adaptive radiation therapy ID RADIOTHERAPY RESEARCH; MONTE-CARLO; ENVIRONMENT AB Radiation therapy (RT) is a common treatment option for a wide variety of cancer types. Despite significant improvements in this technique over the past years, software tools for research in RT are limited to either expensive, closed, proprietary applications or heterogeneous sets of open-source software packages with limited scope, reliability, and user support. Our SlicerRT toolkit aspires to overcome these limitations by providing an extensive set of RT research tools leveraging the advanced visualization and image analysis features of its base platform 3D Slicer. The SlicerRT toolkit comprises of a set of 3D Slicer extensions: SlicerRT core, Matlab Bridge, Multi-dimensional Data, and Gel Dosimetry. The SlicerRT core extension contains 26 modules, many of which provide common RT tools used in most RT research scenarios. Matlab Bridge provides a convenient way for connecting the researchers' existing MATLAB algorithms to the SlicerRT ecosystem. Multi-dimensional Data offers a feature set for handling multi-dimensional datasets, such as longitudinal studies or 4D data. Finally, Gel Dosimetry facilitates gel dosimetry analysis workflows through a streamlined, workflow-based end-user application. It serves as an example and proof of concept for such applications implementing advanced clinical or research workflows. Using these open-source software tools makes it possible to conduct cutting edge RT research without parallel development efforts. It acts as a medium into which researchers can integrate their methods into, and which they can use to perform comparative validation, develop novel RT techniques, or transition advanced methods into routine clinical practice. C1 [Pinter, Csaba; Lasso, Andras; Fichtinger, Gabor] Queens Univ, Sch Comp, Lab Percutaneous Surg, Kingston, ON, Canada. [Wang, An; Jaffray, David] Univ Hlth Network, Princess Margaret Canc Ctr, Radiat Med Program, Toronto, ON, Canada. [Sharp, Gregory C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Alexander, Kevin] Queens Univ, Dept Phys Engn Phys & Astrophys, Kingston, ON, Canada. [Jaffray, David] Univ Hlth Network, Techna Inst Adv Technol Hlth, Toronto, ON, Canada. RP Pinter, C (reprint author), Queens Univ, 25 Union St, Kingston, ON, Canada. EM csaba.pinter@queensu.ca NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1680-0737 BN 978-3-319-19387-8; 978-3-319-19386-1 J9 IFMBE PROC PY 2015 VL 51 BP 622 EP 625 DI 10.1007/978-3-319-19387-8_152 PG 4 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BF5AQ UT WOS:000381813000152 ER PT S AU Altundal, Y Sajo, E Makrigiorgos, GM Berbeco, RI Ngwa, W AF Altundal, Yucel Sajo, Erno Makrigiorgos, G. Mike Berbeco, Ross I. Ngwa, Wilfred BE Jaffray, DA TI Nanoparticle-aided Radiotherapy for Retinoblastoma and Choroidal Melanoma SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2 SE IFMBE Proceedings LA English DT Proceedings Paper CT World Congress on Medical Physics and Biomedical Engineering CY JUN 07-12, 2015 CL Toronto, CANADA DE Nanoparticles; Retinoblastoma; Choroidal Meanoma; Dose Enhancement ID STEREOTACTIC RADIOSURGERY; MACULAR DEGENERATION; GOLD NANOPARTICLES; BRACHYTHERAPY; ENHANCEMENT AB This work investigates the dosimetric feasibility of employing gold nanoparticles (AuNPs) or carboplatin nanoparticles (CNPs) to enhance radiotherapy (RT) treatment efficacy for ocular cancers: retinoblastoma (Rb) and choroidal melanoma (CM), during kV-energy internal and external beam radiotherapy. The results predict that substantial dose enhancement may be achieved by employing AuNPs or CNPs in conjunction with radiotherapy for ocular cancer using kVenergy photon beams. Brachytherapy sources yield higher dose enhancement than the external beam in kV energy range. However, the external beam has the advantage of being non-invasive. C1 [Altundal, Yucel; Sajo, Erno; Ngwa, Wilfred] Univ Massachusetts, Lowell, MA 01852 USA. [Makrigiorgos, G. Mike; Berbeco, Ross I.; Ngwa, Wilfred] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Makrigiorgos, G. Mike; Berbeco, Ross I.; Ngwa, Wilfred] Harvard Med Sch, Boston, MA USA. RP Altundal, Y (reprint author), Univ Massachusetts, Lowell, MA 01852 USA. FU NCI NIH HHS [K01 CA172478] NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1680-0737 BN 978-3-319-19387-8; 978-3-319-19386-1 J9 IFMBE PROC PY 2015 VL 51 BP 907 EP 910 DI 10.1007/978-3-319-19387-8_221 PG 4 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BF5AQ UT WOS:000381813000221 PM 28003818 ER PT S AU Cifter, G Altundal, Y Detappe, A Sajo, E Berbeco, R Makrigiorgos, M Ngwa, W AF Cifter, Gizem Altundal, Yucel Detappe, Alex Sajo, Erno Berbeco, Ross Makrigiorgos, Mike Ngwa, Wilfred BE Jaffray, DA TI Dose enhancement during concomitant chemoradiotherapy using FDA approved concentrations of carboplatin and oxaliplatin nanoparticles SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2 SE IFMBE Proceedings LA English DT Proceedings Paper CT World Congress on Medical Physics and Biomedical Engineering CY JUN 07-12, 2015 CL Toronto, CANADA DE carboplatin; oxaliplatin; dose enhancement; nano particles; concomitant chemoradiotherapy ID VASCULAR DISRUPTING AGENTS; GOLD NANOPARTICLES; RADIATION-THERAPY; PHOTON BEAMS; CANCER; BRACHYTHERAPY; PROLIFERATION; CHEMOTHERAPY; ANGIOGENESIS; DELIVERY AB Radiation boosting has been shown in a number of studies to be effective in the prevention of cancer recurrence. To further the effectiveness of this technique, we propose a new method of enhancing dose locally by administrating nanoparticles of carboplatin (CaNPs) and oxaliplatin (ONPs) as adjuvants to brachytherapy and external beam therapy (EBRT). To investigate the efficacy of this method, dose enhancement calculations were carried out to calculate the energy deposited by photoelectrons and Auger electrons produced by low energy photons from either EBRT or brachytherapy sources with CaNPs and ONPs. Our results show a significant increase in the dose enhancement for various carboplatin and oxaliplatin concentrations up to their allowed FDA limits. C1 [Cifter, Gizem; Altundal, Yucel; Sajo, Erno; Ngwa, Wilfred] Univ Massachusetts, Dept Phys & Appl Phys, Lowell, MA 01854 USA. [Cifter, Gizem; Detappe, Alex; Berbeco, Ross; Makrigiorgos, Mike; Ngwa, Wilfred] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Cifter, Gizem; Detappe, Alex; Berbeco, Ross; Makrigiorgos, Mike; Ngwa, Wilfred] Harvard Med Sch, Boston, MA 02215 USA. RP Cifter, G (reprint author), Univ Massachusetts, Dept Phys & Appl Phys, Lowell, MA 01854 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1680-0737 BN 978-3-319-19387-8; 978-3-319-19386-1 J9 IFMBE PROC PY 2015 VL 51 BP 1723 EP 1726 DI 10.1007/978-3-319-19387-8_418 PG 4 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BF5AQ UT WOS:000381813000418 ER PT S AU Best, SR Pai, SI AF Best, Simon R. Pai, Sara I. BE Fakhry, C DSouza, G TI The Role of Vaccines for HPV-Related Head and Neck Cancers SO HPV AND HEAD AND NECK CANCERS SE Head and Neck Cancer Clinics LA English DT Article; Book Chapter ID HUMAN-PAPILLOMAVIRUS TYPE-16; CERVICAL INTRAEPITHELIAL NEOPLASIA; T-CELL RESPONSES; TUMOR-SPECIFIC IMMUNITY; INTERFERON-ALPHA; UNITED-STATES; RISK-FACTORS; DNA VACCINE; PHASE-I; INFECTION C1 [Best, Simon R.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Pai, Sara I.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Pai, Sara I.] Harvard Med Sch, Boston, MA USA. RP Best, SR (reprint author), Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. EM sbest2@jhmi.edu; Sara.Pai@mgh.harvard.edu NR 63 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER INDIA PI NEW DELHI PA 7TH FLOOR, VIJAYA BUILDING, 17, BARAKHAMBA RD, NEW DELHI, 110 001, INDIA SN 2364-4079 BN 978-81-322-2413-6; 978-81-322-2412-9 J9 HEAD NECK CANC CLIN PY 2015 BP 99 EP 110 DI 10.1007/978-81-322-2413-6_7 D2 10.1007/978-81-322-2413-6 PG 12 WC Oncology; Otorhinolaryngology SC Oncology; Otorhinolaryngology GA BF4RY UT WOS:000381637300010 ER PT S AU Chatnuntawech, I Bilgic, B Martin, A Setsompop, K Adalsteinsson, E AF Chatnuntawech, Itthi Bilgic, Berkin Martin, Adrian Setsompop, Kawin Adalsteinsson, Elfar GP IEEE TI FAST RECONSTRUCTION FOR ACCELERATED MULTI-SLICE MULTI-CONTRAST MRI SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 12th International Symposium on Biomedical Imaging CY APR 16-19, 2015 CL New York, NY SP NIBIB, NATL INST, IEEE, EMB DE Magnetic resonance imaging (MRI); compressed sensing; multi-contrast imaging ID IMAGE-RECONSTRUCTION AB Clinical magnetic resonance imaging (MRI) protocols typically include multiple acquisitions of the same region of interest under different contrast settings. This paper presents an efficient algorithm to jointly reconstruct a set of undersampled images with different contrasts. The proposed method has faster reconstruction time and better quality as measured by the normalized root-mean-square error (RMSE) compared to the existing methods consisting of multi-contrast Fast Composite Splitting Algorithm (FCSA-MT), Multiple measurement vectors FOCal Underdetermined System Solver (M-FOCUSS), and total variation regularized compressed sensing (SparseMRI). To efficiently solve the l(2,1)-regularized optimization problem, our proposed algorithm adopts the Split Bregman (SB) technique to divide the problem into sub-problems. We efficiently compute a closed-form solution to each of the sub-problems by implementing a 3D spatial gradient operator as element-wise multiplication in k-space. As demonstrated by the in vivo results, the proposed algorithm (SB-L21) offers 2x, 32x, and 66x faster reconstruction with lower RMSE averaged across all contrasts and slices compared to FCSA-MT, M-FOCUSS, and SparseMRI, respectively. C1 [Chatnuntawech, Itthi; Martin, Adrian; Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Bilgic, Berkin; Setsompop, Kawin] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Martin, Adrian] Univ Rey Juan Carlos, Appl Math, Mostoles, Spain. [Setsompop, Kawin] Harvard Med Sch, Dept Radiol, Boston, MA USA. [Adalsteinsson, Elfar] MIT, Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Chatnuntawech, I (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2374-8 J9 I S BIOMED IMAGING PY 2015 BP 335 EP 338 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BF3IK UT WOS:000380546000080 ER PT S AU Zhao, B Lam, F Bilgicy, B Ye, HH Setsompop, K AF Zhao, Bo Lam, Fan Bilgicy, Berkin Ye, Huihui Setsompop, Kawin GP IEEE TI y MAXIMUM LIKELIHOOD RECONSTRUCTION FOR MAGNETIC RESONANCE FINGERPRINTING SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 12th International Symposium on Biomedical Imaging CY APR 16-19, 2015 CL New York, NY SP NIBIB, NATL INST, IEEE, EMB DE Magnetic resonance fingerprinting; maximum likelihood estimation; iterative reconstruction; variable splitting; alternating direction method of multiplier; variable projection AB In this paper, we introduce a statistical estimation framework for magnetic resonance fingerprinting (MRF), a recently proposed quantitative imaging paradigm. Within this framework, we present a maximum likelihood formulation to simultaneously estimate multiple parameter maps from highly undersampled, noisy k-space data. A novel iterative algorithm, based on variable splitting, the alternating direction method of multipliers, and the variable projection method, is proposed to solve the resulting optimization problem. Representative results demonstrate that compared to the conventional MRF reconstruction, the proposed method yields improved accuracy and/or reduced acquisition time. Moreover, the proposed formulation enables theoretical analysis of MRF. For example, we show that with the gridding reconstruction as an initialization, the first iteration of the proposed method exactly produces the conventional MRF reconstruction. C1 [Zhao, Bo; Lam, Fan] Univ Illinois, Dept Elect & Comp Engn, Champaign, IL 61820 USA. [Bilgicy, Berkin; Ye, Huihui; Setsompop, Kawin] Massachusetts Gen Hosp, Athinoula A Martions Ctr Biomed Imaging, Boston, MA 02114 USA. [Bilgicy, Berkin; Ye, Huihui; Setsompop, Kawin] Harvard Med Sch, Boston, MA USA. RP Zhao, B (reprint author), Univ Illinois, Dept Elect & Comp Engn, Champaign, IL 61820 USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2374-8 J9 I S BIOMED IMAGING PY 2015 BP 905 EP 909 PG 5 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BF3IK UT WOS:000380546000216 ER PT S AU Jafari-Khouzani, K Gerstner, E Rosen, B Kalpathy-Cramer, J AF Jafari-Khouzani, Kourosh Gerstner, Elizabeth Rosen, Bruce Kalpathy-Cramer, Jayashree GP IEEE TI UPSAMPLING DYNAMIC CONTRAST ENHANCED MRI SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 12th International Symposium on Biomedical Imaging CY APR 16-19, 2015 CL New York, NY SP NIBIB, NATL INST, IEEE, EMB DE Interpolation; upsampling; super-resolution; dynamic contrast-enhanced magnetic resonance imaging AB Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used to evaluate the vasculature properties of tissues. The resolution of DCE-MRI is limited since the imaging is required to be rapid in order to achieve a reasonable temporal resolution. This limits the accuracy of quantitative analysis of DCE-MRI, in particular, voxel-wise analysis. In this paper, we propose an upsampling technique that uses high-resolution post-Gadolinium T1-weighted image to guide interpolation of DCE-MRI to a higher resolution. Experimental results conducted on brain DCE-MRI of patients with brain tumors show the superiority of the method in comparison with standard interpolation techniques. C1 [Jafari-Khouzani, Kourosh; Rosen, Bruce; Kalpathy-Cramer, Jayashree] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Gerstner, Elizabeth] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Jafari-Khouzani, K (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2374-8 J9 I S BIOMED IMAGING PY 2015 BP 1032 EP 1035 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BF3IK UT WOS:000380546000246 ER PT S AU Zhu, WT Guo, N Bai, B Conti, PS Leahy, RM Li, QZ AF Zhu, Wentao Guo, Ning Bai, Bing Conti, Peter S. Leahy, Richard M. Li, Quanzheng GP IEEE TI Direct Estimation from List-Mode Data for Reversible Tracers using Graphical Modeling SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 12th International Symposium on Biomedical Imaging CY APR 16-19, 2015 CL New York, NY SP NIBIB, NATL INST, IEEE, EMB ID PET DATA; DYNAMIC PET; RECONSTRUCTION; BINDING AB We propose a novel method to directly estimate parametric images from listmode PET data for reversible tracers based on an inhomogeneous Poisson process model. We use a relative equilibrium graphical model, similar to the Logan plot, to linearize the problem. A static sinogram from time of tracer injection to the steady state is incorporated to improve the ill-conditioning of the estimation problem. Cramer-Rao analysis and Monte-Carlo simulation demonstrate that our method improves the conditioning of the estimation problem and provides higher contrast recovery and smaller standard deviation compared with a sinogram based direct estimation approach. C1 [Zhu, Wentao; Bai, Bing; Conti, Peter S.; Leahy, Richard M.] Univ Southern Calif, Los Angeles, CA 90089 USA. [Guo, Ning; Li, Quanzheng] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. RP Zhu, WT (reprint author), Univ Southern Calif, Los Angeles, CA 90089 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2374-8 J9 I S BIOMED IMAGING PY 2015 BP 1204 EP 1207 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BF3IK UT WOS:000380546000288 ER PT S AU Hoge, WS Polimeni, JR AF Hoge, W. Scott Polimeni, Jonathan R. GP IEEE TI A DUAL-POLARITY GRAPPA KERNEL FOR THE ROBUST RECONSTRUCTION OF ACCELERATED EPI DATA SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 12th International Symposium on Biomedical Imaging CY APR 16-19, 2015 CL New York, NY SP NIBIB, NATL INST, IEEE, EMB DE EPI; Nyquist Ghost Correction; parallel imaging; fMRI; Artifact Correction AB The quality of high-resolution Echo Planar images of the human brain has improved greatly in recent years, enabled by novel multi-channel receiver coil arrays and parallel imaging. However, in regions with local field inhomogeneity, EPI artifacts limit which parts of the brain can be imaged successfully. In this work, we present evidence that certain image artifacts can be attributed to nonlinear phase errors that are present in regions of local susceptibility gradients and certain coil array elements. Because these phase errors cannot be corrected with conventional Nyquist ghost correction, we propose a new method that integrates ghost correction with parallel imaging reconstruction. The proposed Dual-Polarity GRAPPA method operates directly on raw EPI data to estimate k-space data from the under-sampled acquisition while simultaneously correcting inherent EPI phase errors. We present examples of this method successfully removing strong phase-error artifacts in high-resolution 7T EPI data. C1 [Hoge, W. Scott] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Hoge, W. Scott] Harvard Med Sch, Boston, MA USA. [Polimeni, Jonathan R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Hoge, WS (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 11 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2374-8 J9 I S BIOMED IMAGING PY 2015 BP 1244 EP 1247 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BF3IK UT WOS:000380546000298 ER PT S AU Dutta, J El Fakhri, G Zhu, XP Li, QZ AF Dutta, Joyita El Fakhri, Georges Zhu, Xuping Li, Quanzheng GP IEEE TI PET POINT SPREAD FUNCTION MODELING AND IMAGE DEBLURRING USING A PET/MRI JOINT ENTROPY PRIOR SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 12th International Symposium on Biomedical Imaging CY APR 16-19, 2015 CL New York, NY SP NIBIB, NATL INST, IEEE, EMB DE deblurring; deconvolution; joint entropy; anatomical priors; PET/MRI; multimodality imaging; partial volume correction ID ANATOMICAL PRIORS; RECONSTRUCTION; DECONVOLUTION; INFORMATION; RESOLUTION AB The quantitative accuracy of PET is degraded by partial volume effects caused by the limited spatial resolution capabilities of PET scanners. In this paper, we describe an image deblurring technique that uses the spatially varying point spread function of the scanner measured in the image space. To stabilize the deconvolution problem, we introduce the joint entropy between the PET image and a high resolution MR image as an information theoretic penalty function. We present a computationally efficient framework for minimizing the resultant cost function. By means of simulations on the Brain-Web phantom, we show that our method leads to faster convergence and a lower mean squared error. We then applied our method to a phantom and a human dataset and demonstrated that, compared to standalone deblurring, which tends to amplify noise, the joint entropy prior leads to a smooth PET image with sharp boundaries consistent with MRI. C1 [Dutta, Joyita; El Fakhri, Georges; Zhu, Xuping; Li, Quanzheng] Harvard Med Sch, Ctr Adv Med Imaging Sci, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dutta, J (reprint author), Harvard Med Sch, Ctr Adv Med Imaging Sci, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 1 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2374-8 J9 I S BIOMED IMAGING PY 2015 BP 1423 EP 1426 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BF3IK UT WOS:000380546000342 ER PT S AU Bolon-Canedo, V Ataer-Cansizoglu, E Erdogmus, D Kalpathy-Cramer, J Chiang, MF AF Bolon-Canedo, V. Ataer-Cansizoglu, E. Erdogmus, D. Kalpathy-Cramer, J. Chiang, M. F. GP IEEE TI A GMM-BASED FEATURE EXTRACTION TECHNIQUE FOR THE AUTOMATED DIAGNOSIS OF RETINOPATHY OF PREMATURITY SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 12th International Symposium on Biomedical Imaging CY APR 16-19, 2015 CL New York, NY SP NIBIB, NATL INST, IEEE, EMB DE Retinopathy of prematurity; feature extraction; classification ID PLUS DISEASE DIAGNOSIS; IMAGE-ANALYSIS; AGREEMENT AB Retinopathy of Prematurity (ROP) is an ophthalmic disease that is a leading cause of childhood blindness throughout the world. Accurate diagnosis of ROP is vital to identify infants who require treatment, which can prevent blindness. Arterial tortuosity and venous dilation in the retina are important signs of ROP, so it is necessary to extract these features from points on the vessels or vessel segments. Then, an image is represented with statistics such as minimum, maximum or mean of these values. However, these statistics provide biased estimates as an image contains both healthy and abnormal vessels. In this work, we present a novel feature extraction technique that represents each image with the parameters of a two-component Gaussian Mixture Model (GMM). Using these features, we performed classification experiments on a manually segmented retinal image dataset consisting of 77 images. The results show that GMM-based features outperform other features that are based on classical statistics, with accuracy over 90%. Moreover, if the features are extracted from the whole image without distinguishing veins and arteries, proposed features provide better performance compared to using traditional statistics. C1 [Bolon-Canedo, V.] Univ A Coruna, Dept Comp Sci, La Coruna, Spain. [Ataer-Cansizoglu, E.; Erdogmus, D.] Northeastern Univ, Cognit Syst Lab, Boston, MA 02115 USA. [Kalpathy-Cramer, J.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Chiang, M. F.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Chiang, M. F.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Bolon-Canedo, V (reprint author), Univ A Coruna, Dept Comp Sci, La Coruna, Spain. RI Bolon-Canedo, Veronica/A-5573-2015; OI Bolon-Canedo, Veronica/0000-0002-0524-6427; Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 NR 17 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2374-8 J9 I S BIOMED IMAGING PY 2015 BP 1498 EP 1501 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BF3IK UT WOS:000380546000360 ER PT S AU Ataer-Cansizoglu, E Taguchi, Y Kalpathy-Cramer, J Chiang, MF Erdogmus, D AF Ataer-Cansizoglu, E. Taguchi, Y. Kalpathy-Cramer, J. Chiang, M. F. Erdogmus, D. GP IEEE TI ANALYSIS OF SHAPE ASSUMPTIONS IN 3D RECONSTRUCTION OF RETINA FROM MULTIPLE FUNDUS IMAGES SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 12th International Symposium on Biomedical Imaging CY APR 16-19, 2015 CL New York, NY SP NIBIB, NATL INST, IEEE, EMB DE retinal images; 3D reconstruction; visualization AB Utilizing priors about the shape of retinal surface is important for accurate reconstruction. We present a detailed analysis of geometrical shape priors in the 3D reconstruction of retina. We first approximate the retinal surface either as a sphere inspired by the actual shape of the eyeball, or as a plane inspired by the 2D mosaicing approaches. Based on this approximation, we perform an initial camera localization with a 2D -to 3D registration procedure. Then, parameters of the surface and the camera poses are refined through a nonlinear least squares optimization using different shape priors. The resulting 3D model and camera poses can be used for intuitively visualizing the retinal images with a model -guided browsing interface. C1 [Ataer-Cansizoglu, E.; Erdogmus, D.] Northeastern Univ, Cognit Syst Lab, Boston, MA 02115 USA. [Taguchi, Y.] MERL, Cambridge, MA USA. [Kalpathy-Cramer, J.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Chiang, M. F.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Chiang, M. F.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Ataer-Cansizoglu, E (reprint author), Northeastern Univ, Cognit Syst Lab, Boston, MA 02115 USA. OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2374-8 J9 I S BIOMED IMAGING PY 2015 BP 1502 EP 1505 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BF3IK UT WOS:000380546000361 ER PT J AU Nossenson, R Nossenson, N AF Nossenson, Ronit Nossenson, Nir BE Avresky, DR Busnel, Y TI Packet Erasure Multi-Channel Model for Video Streaming Applications SO 2015 IEEE 14th International Symposium on Network Computing and Applications (NCA) LA English DT Proceedings Paper CT IEEE 14th International Symposium on Network Computing and Applications NCA CY SEP 28-30, 2015 CL Cambridge, MA SP IEEE Computer Society Technical Committee on Distributed Processing (TCDP), Akamai Technologies, Inc., International Research Institute on Autonomic Network Computing DE Video Streaming Applications; Multichannel Video Steaming; Packet Erasure Models ID AD HOC NETWORKS; CHANNEL AB Transmission of a video stream over multiple channels is an emerging technology for improving the streaming quality over wireless and best-effort networks. However, these channels might be statistically dependent and may share resources such as bottleneck links, or may cause mutual interference. As a result, the packet loss rate and packet delay over a specific channel can increase while activating additional channels. Modeling such a system without consideration of the negative impact of the channels statistical dependency can lead to underestimation of service performance problems. We suggest a new simple Markov model for multiple channels with statistical dependency. The suggested model captures the performance degradation over the individual channels, while activating multiple channels. Traces of real data are used to confirm the model validity. C1 [Nossenson, Ronit] Akamai Technol, Serv Performance, Cambridge, MA 02142 USA. [Nossenson, Nir] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Nossenson, Nir] Harvard Med Sch, Boston, MA USA. RP Nossenson, R (reprint author), Akamai Technol, Serv Performance, Cambridge, MA 02142 USA. EM rnossens@akamai.com; nnossenson@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-5090-1849-9 PY 2015 BP 259 EP 262 DI 10.1109/NCA.2015.50 PG 4 WC Computer Science, Information Systems SC Computer Science GA BF3BW UT WOS:000380522500040 ER PT J AU Nabavi, S Beck, AH AF Nabavi, Sheida Beck, Andrew H. GP IEEE TI Earth Mover's Distance for Differential Analysis of Heterogeneous Genomics Data SO 2015 IEEE GLOBAL CONFERENCE ON SIGNAL AND INFORMATION PROCESSING (GLOBALSIP) LA English DT Proceedings Paper CT IEEE Global Conference on Signal and Information Processing (GlobalSIP) CY DEC 13-16, 2015 CL Orlando, FL DE Earth mover's distance; differential expression analysis; distribution comparison; heterogeneous samples ID EXPRESSION ANALYSIS; GENE AB The identification of mRNA transcripts with expression levels associated with clinical and/or biological entities is a major goal of biomedical research. Several methods have been developed to identify genes expressed differentially between biological or clinical classes of interest. These methods use statistical approaches and are based on the assumption that between classes variations are high and within class variation is low. However, many problems in biology and biomedicine contain samples that show high levels of within class heterogeneity. This makes the identification of differentially expressed genes very challenging. To address this challenge we developed a differential expression analysis method based on a signal processing approach that uses the Earth Mover's Distance to measure the overall difference between the distributions of a gene's expression in two classes of samples and uses permutations to estimate the false discovery rate for each gene. Applying this method to simulated and real biological data, we show that this method outperforms the conventional differential expression analysis methods. C1 [Nabavi, Sheida] Univ Connecticut, Dept Comp Sci & Engn, Storrs, CT 06269 USA. [Beck, Andrew H.] BIDMC, Dept Pathol, Boston, MA USA. [Beck, Andrew H.] Harvard Med Sch, Boston, MA USA. RP Nabavi, S (reprint author), Univ Connecticut, Dept Comp Sci & Engn, Storrs, CT 06269 USA. EM nabavi@engr.uconn.edu; abeck2@bidmc.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-7591-4 PY 2015 BP 963 EP 966 PG 4 WC Computer Science, Artificial Intelligence SC Computer Science GA BF2LH UT WOS:000380477600197 ER PT J AU Litz, B AF Litz, Brett TI Early intervention for trauma and loss: overview and working care model SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Meeting Abstract ID POSTTRAUMATIC-STRESS; TRAJECTORIES; RESILIENCE; DISORDER C1 [Litz, Brett] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA. [Litz, Brett] Boston Univ, Coll Arts & Sci, Dept Psychol, Boston, MA 02215 USA. [Litz, Brett] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. EM brettlitz@comcast.net FU Swedish Foundation for Humanities and Social Sciences [F14-1747:1] FX This conference was funded by a grant from The Swedish Foundation for Humanities and Social Sciences (F14-1747:1). NR 13 TC 2 Z9 2 U1 0 U2 1 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2015 VL 6 SU 3 AR 28543 DI 10.3402/ejpt.v6.28543 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DR6JI UT WOS:000380007800002 PM 26073207 ER PT S AU Citi, L Olariu, C Barbieri, R AF Citi, Luca Olariu, Claudia Barbieri, Riccardo BE Murray, A TI A LightWAVE client for Semi-automated Annotation of Heart Beats from ECG Time Series SO 2015 COMPUTING IN CARDIOLOGY CONFERENCE (CINC) SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 2015 Comp in Cardiol Conference (CinC) CY SEP 06-09, 2015 CL Comp in Cardiol 2015, nice, FRANCE HO Comp in Cardiol 2015 AB LightWAVE is an open-source web-based software for viewing ECGs and other physiologic waveforms and associated annotations (such as heart-beat markers). At present, most users run the raw ECG through an automated QRS detector and later use LightWAVE to review and correct the detected heart beats. Although this 2-stage procedure may work well with clean signals, it is inefficient and time consuming when the recordings are contaminated by noise, artefacts or recurring ectopic events. To overcome this limitation, we customized the LightWAVE client to allow automated and semi-automated annotation of heart beats from ECG time series. In semi-automatic mode, the algorithm automatically identifies most QRS complexes and stops - asking for manual intervention - whenever the confidence of a detection falls below a given threshold. Additionally, the software now shows the series of inter-beat intervals, which is an invaluable tool to easily spot R-wave misdetections and genuine arrhythmias. The new client introduces further additional features compared to the standard version, for example the possibility of importing raw signals from local CSV files and of exporting the current plot in SVG format. Overall, our customized client extends the functionality of LightWAVE and brings it closer to one of its design goals, i.e. to provide a comfortable and efficient method of annotating physiologic data. C1 [Citi, Luca; Olariu, Claudia] Univ Essex, Sch Elect Engn & Comp Sci, Wivenhoe Pk, Colchester CO4 3SQ, Essex, England. [Barbieri, Riccardo] Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA USA. [Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Citi, L (reprint author), Univ Essex, Sch Elect Engn & Comp Sci, Wivenhoe Pk, Colchester CO4 3SQ, Essex, England. EM lciti@ieee.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-5090-0685-4 J9 COMPUT CARDIOL CONF PY 2015 VL 42 BP 605 EP 608 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical SC Computer Science; Engineering GA BF1CZ UT WOS:000380374700153 ER PT S AU Garcia, RG Valenza, G Tomaz, CA Barbieri, R AF Garcia, Ronald G. Valenza, Gaetano Tomaz, Carlos A. Barbieri, Riccardo BE Murray, A TI Instantaneous Bispectral Analysis of Heartbeat Dynamics for the Assessment of Major Depression SO 2015 COMPUTING IN CARDIOLOGY CONFERENCE (CINC) SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 2015 Comp in Cardiol Conference (CinC) CY SEP 06-09, 2015 CL Comp in Cardiol 2015, nice, FRANCE HO Comp in Cardiol 2015 ID BIPOLAR PATIENTS; RESPONSES; STATES AB Major depression (MD) is associated with increased cardiovascular risk. Although alterations in autonomic regulation have been proposed as one potential pathophysiological mechanism to explain this comorbidity, studies using standard HRV features in depressed subjects have been inconclusive. In this study, 48 patients with MD and 48 healthy controls (TIC) were randomly assigned to an audio-visual task with two different versions: one emotionally neutral (A) and the other emotionally arousing (E). ECG signal (lead was collected at 250 Hz, and point process nonlinear analysis of heartbeat dynamics was performed to obtain instantaneous features from standard time-domain analysis, as well as spectral (LF, HF, LF/HF) and bispectral (LL, LH, and TIN) analysis, 2ilean values of all features were computed over the 30s segment of the emotional elicitation session, Only bispectral parameters LH and NH were significantly different between patients and NC (p<0.02,1. Our results suggest that time-varying nonlinear dynamics of parasympathetic activity are significantly reduced in MD compared to HC in response to emotional elicitation. We conclude that instantaneous bispectral analysis could be a promising tool for assessment of autonomic modulation in MD, C1 [Garcia, Ronald G.; Valenza, Gaetano; Barbieri, Riccardo] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Garcia, Ronald G.] Univ Santander, Sch Med, Bucaramanga, Colombia. [Valenza, Gaetano] Univ Pisa, Res Ctr E Piaggio, Pisa, Italy. [Tomaz, Carlos A.] Univ Brasilia, Lab Neurosci & Behav, Brasilia, DF, Brazil. RP Garcia, RG (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, CNY 149-2301,13th St, Charlestown, MA 02129 USA. EM rgarcia@nmr.mgh.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-5090-0685-4 J9 COMPUT CARDIOL CONF PY 2015 VL 42 BP 781 EP 784 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical SC Computer Science; Engineering GA BF1CZ UT WOS:000380374700197 ER PT S AU Valenza, G Faita, F Pratali, L Vanello, N Lanata, A Barbieri, R Scilingo, EP AF Valenza, Gaetano Faita, Francesco Pratali, Lorenza Vanello, Nicola Lanata, Antonio Barbieri, Riccardo Scilingo, Enzo Pasquale BE Murray, A TI Changes in Instantaneous Complex Dynamics during Exercise in Chronic Mountain Sickness SO 2015 COMPUTING IN CARDIOLOGY CONFERENCE (CINC) SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 2015 Comp in Cardiol Conference (CinC) CY SEP 06-09, 2015 CL Comp in Cardiol 2015, nice, FRANCE HO Comp in Cardiol 2015 ID HEART AB The combination of persistent polycythemia with decreased physical and cognitive performances while living in high-altitude is defined as 'Chronic Mountain Sickness' (CMS). To date, the role of the autonomic nervous system in CMS is still unknown. In this study, we analyze instantaneous tracking of cardiovascular complexity in order to increase the knowledge on CMS physio-pathology. To this extent, we processed heartbeat dynamics gathered from 13 CMS males and 7 high-altitude male dwellers, taken as healthy controls (HC), during semi-supine bicycle tasks performed at 25W, 50W, and 100W along with a recovery session. Instantaneous Dominant Lyapunov exponents (IDLE), as estimated through point-process nonlinear models with Laguerre and Volterra expansions, were evaluated from such series. Results showed that instantaneous heartbeat complex dynamics was significantly altered in CMS. In particular, IDLE increases were associated to CMS, with respect to HC, during the 25W and 50W exercise sessions (p < 0.01). Conversely, no statistical differences were found when analyzing the 100W session, and first recovery after exercise. C1 [Valenza, Gaetano; Vanello, Nicola; Lanata, Antonio; Scilingo, Enzo Pasquale] Univ Pisa, Dept Informat Engn, Pisa, Italy. [Valenza, Gaetano; Vanello, Nicola; Lanata, Antonio; Scilingo, Enzo Pasquale] Univ Pisa, Res Ctr E Piaggio, Pisa, Italy. [Valenza, Gaetano; Barbieri, Riccardo] Harvard Med School, Massachusetts Gen Hosp, Boston, MA USA. [Faita, Francesco; Pratali, Lorenza; Vanello, Nicola] Italian Natl Res Council, Inst Clin Physiol, Pisa, Italy. RP Valenza, G (reprint author), Largo Lucio Lazzarino 1, I-56122 Pisa, Italy. EM g.valenza@ieee.org NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-5090-0685-4 J9 COMPUT CARDIOL CONF PY 2015 VL 42 BP 997 EP 1000 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical SC Computer Science; Engineering GA BF1CZ UT WOS:000380374700251 ER PT S AU Barbieri, R Valenza, G Citi, L Placidi, F Izzi, F Albanese, M Marciani, MG Guerrisi, M Romigi, A Toschi, N AF Barbieri, Riccardo Valenza, Gaetano Citi, Luca Placidi, Fabio Izzi, Francesca Albanese, Maria Marciani, Maria Grazia Guerrisi, Maria Romigi, Andrea Toschi, Nicola BE Murray, A TI Lower Instantaneous Entropy of Heartbeat Dynamics During Seizures in Untreated Temporal Lobe Epilepsy SO 2015 COMPUTING IN CARDIOLOGY CONFERENCE (CINC) SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 2015 Comp in Cardiol Conference (CinC) CY SEP 06-09, 2015 CL Comp in Cardiol 2015, nice, FRANCE HO Comp in Cardiol 2015 ID RATE-VARIABILITY; STATES AB Temporal lobe epilepsy (TLE) is associated with dysunction of the autonomic nervous system. While it is known that heart rate variability (HRV) changes in epilepsy comprise both ictal (CRI) and interictal (INT) autonomic cardiac effects, the mechanisms leading to these alterations are not well understood. In this paper we investigate the alterations in instantaneous autonomic complexity during CRI in untreated TLE using bipolar ECG recordings from 10 patients with at least one seizure originating from temporal regions as recorded by video-EEG monitoring. We isolated artifact-free INT and CRI periods and computed mean values of instantaneous point-process Approximate and Sample Entropy (ipApEn and ipSampEn, respectively). ipApEn was significantly lower (p<0.02) and ipSampEn was lower (p<0.065) in CRI vs. INT. The variability (median absolute deviation) of ipApEn was also significantly lower (p<0.03) in CRI vs INT. Our results suggest that ictal events in untreated TLE are associated with a decrease in heartbeat complexity and its variability, possibly pointing toward subtle autonomic changes which may accompany or precede seizures, and can only be detected using an instantaneous, time resolved approach to quantifying autonomic complexity. C1 [Barbieri, Riccardo; Valenza, Gaetano; Toschi, Nicola] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Valenza, Gaetano] Univ Pisa, Pisa, Italy. [Citi, Luca] Univ Essex, Colchester, Essex, England. [Placidi, Fabio; Marciani, Maria Grazia; Guerrisi, Maria; Toschi, Nicola] Univ Roma Tor Vergata, Rome, Italy. [Placidi, Fabio; Izzi, Francesca; Albanese, Maria; Marciani, Maria Grazia; Romigi, Andrea] Tor Vergata Univ Hosp, Rome, Italy. RP Barbieri, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM barbieri@neurostat.mit.edu NR 19 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-5090-0685-4 J9 COMPUT CARDIOL CONF PY 2015 VL 42 BP 1037 EP 1040 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical SC Computer Science; Engineering GA BF1CZ UT WOS:000380374700261 ER PT S AU Simoes, RD Mitsiades, C Williamson, KE Emmert-Streib, F AF Simoes, Ricardo de Matos Mitsiades, Constantine Williamson, Kate E. Emmert-Streib, Frank BE Huan, J Miyano, S Shehu, A Hu, X Ma, B Rajasekaran, S Gombar, VK Schapranow, IM Yoo, IH Zhou, JY Chen, B Pai, V Pierce, B TI Network signatures based on gene pair expression ratios improve classification and the analysis of muscle-invasive urothelial cancer SO PROCEEDINGS 2015 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM LA English DT Proceedings Paper CT IEEE International Conference on Bioinformatics and Biomedicine CY NOV 09-12, 2015 CL Washington, DC SP IEEE, IEEE Comp Soc, Natl Sci Fdn DE Urothelial cancer; muscle-invasive; non muscle-invasive; gene pair expression ratio; feature selection; data feature space inflation ID MOLECULAR INTERACTION DATABASE; BLADDER-CANCER; BREAST-CANCER; VARIABLE SELECTION; 2013 UPDATE; IDENTIFICATION; REGULARIZATION; SURVIVAL; PACKAGE; DISEASE AB Urothelial cancer (UC) is highly recurrent and can progress from non-invasive (NMIUC) to a more aggressive muscle-invasive (MIUC) subtype that invades the muscle tissue layer of the bladder. We present a proof of principle study that network-based features of gene pairs can be used to improve classifier performance and the functional analysis of urothelial cancer gene expression data. In the first step of our procedure each individual sample of a UC gene expression dataset is inflated by gene pair expression ratios that are defined based on a given network structure. In the second step an elastic net feature selection procedure for network-based signatures is applied to discriminate between NMIUC and MIUC samples. We performed a repeated random subsampling cross validation in three independent datasets. The network signatures were characterized by a functional enrichment analysis and studied for the enrichment of known cancer genes. We observed that the network-based gene signatures from meta collections of protein-protein interaction (PPI) databases such as CPDB and the PPI databases HPRD and BioGrid improved the classification performance compared to single gene based signatures. The network based signatures that were derived from PPI databases showed a prominent enrichment of cancer genes (e.g., TP53, TRIM27 and HNRNPA2Bl). We provide a novel integrative approach for large-scale gene expression analysis for the identification and development of novel diagnostical targets in bladder cancer. Further, our method allowed to link cancer gene associations to network-based expression signatures that are not observed in gene-based expression signatures. C1 [Simoes, Ricardo de Matos; Mitsiades, Constantine] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Sch Med Dent & Biomed Sci, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland. [Simoes, Ricardo de Matos; Williamson, Kate E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Emmert-Streib, Frank] Tampere Univ Technol, FI-33720 Tampere, Finland. RP Simoes, RD (reprint author), Queens Univ Belfast, Ctr Canc Res & Cell Biol, Sch Med Dent & Biomed Sci, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland. EM ricardo_dematossimoes@dfci.harvard.edu NR 42 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2156-1125 BN 978-1-4673-6798-1 J9 IEEE INT C BIOINFORM PY 2015 BP 1216 EP 1223 PG 8 WC Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Computer Science; Mathematical & Computational Biology GA BE9EI UT WOS:000377335600212 ER PT S AU Tuerk, PW Ronzio, JL Shore, P AF Tuerk, Peter W. Ronzio, Joseph L. Shore, Peter BE Tuerk, PW Shore, P TI Technologies and Clinical Videoconferencing Infrastructures: A Guide to Selecting Appropriate Systems SO CLINICAL VIDEOCONFERENCING IN TELEHEALTH: PROGRAM DEVELOPMENT AND PRACTICE SE Behavioral Telehealth LA English DT Article; Book Chapter AB Purpose This chapter provides basic and intermediate-level key concepts related to clinical videoconferencing (CV) technologies for the purposes of assisting clinical administrators in choosing a CV system. It defines the common types of CV systems and considers the strengths and limitations of hardware-based vs. software-based platforms, as well as web-based vs. cellular-based signal transmission. The chapter also highlights the importance of defining the specific needs of a clinical ecology on a hierarchy to help achieve a balance between optimizing clinical utility and available budget when choosing CV systems. Context The information is helpful to clinical managers or administrators who are in charge of choosing/purchasing a CV solution for their facility or practice. The field of telehealth, and the availability of accompanying commercial technology options, is expanding rapidly with no end in sight. Both the development of new technologies and the daily identification of novel clinical demands for technologies are fueling continued growth in the field. Accordingly, administrators new to CV purchasing and decision making need a concise starting place to get a handle on relevant issues. The chapter is also helpful to clinicians, as they are ultimately the driving force in the identification of new ways to use technology in the service of public health needs. Tools The chapter provides the following tools: a summary overview of CV system options, including hardware-based, software-based and mixed strategies; a checklist of issues to research when choosing CV systems, a beginners guide to network capacity issues relevant to purchasing CV systems; three vignettes outlining helpful issues related to choosing specific telehealth hardware; a guide for selecting CV software, including the requirements of existing hardware; information on mobile tablets in the CV environment; a detailed discussion regarding health insurance portability and accountability (HIPPA) and FIPS 140-2 encoding; considerations regarding the integration of supporting technologies for CV systems; and a checklist of questions to address basic system needs before consulting with vendors. C1 [Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Tuerk, Peter W.] Vet Hlth Adm, Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Ronzio, Joseph L.] Vet Hlth Adm, Dept Vet Affairs, Washington, DC USA. [Shore, Peter] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Shore, Peter] Dept Vet Affairs, VA NW Hlth Network VISN 20, Portland, OR USA. RP Tuerk, PW (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. EM Tuerk@musc.edu; joe@ronzio.org; shore@ohsu.edu NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2199-8604 BN 978-3-319-08765-8; 978-3-319-08764-1 J9 BEHAV TELEHEALTH PY 2015 BP 3 EP 22 DI 10.1007/978-3-319-08765-8_1 D2 10.1007/978-3-319-08765-8 PG 20 WC Psychology, Clinical; Health Care Sciences & Services; Health Policy & Services; Medical Informatics; Psychiatry SC Psychology; Health Care Sciences & Services; Medical Informatics; Psychiatry GA BF0EP UT WOS:000378626900003 ER PT S AU Tuerk, PW Shore, P AF Tuerk, Peter W. Shore, Peter BE Tuerk, PW Shore, P TI Clinical Videoconferencing in Telehealth Program Development and Practice Preface SO CLINICAL VIDEOCONFERENCING IN TELEHEALTH: PROGRAM DEVELOPMENT AND PRACTICE SE Behavioral Telehealth LA English DT Editorial Material; Book Chapter C1 [Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. [Tuerk, Peter W.] Ralph H Johnson VA Med Ctr, Dept Vet Affairs, Charleston, SC USA. [Shore, Peter] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Shore, Peter] Dept Vet Affairs, VA NW Hlth Network VISN 20, Portland, OR USA. RP Tuerk, PW (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2199-8604 BN 978-3-319-08765-8; 978-3-319-08764-1 J9 BEHAV TELEHEALTH PY 2015 BP IX EP X D2 10.1007/978-3-319-08765-8 PG 2 WC Psychology, Clinical; Health Care Sciences & Services; Health Policy & Services; Medical Informatics; Psychiatry SC Psychology; Health Care Sciences & Services; Medical Informatics; Psychiatry GA BF0EP UT WOS:000378626900002 ER PT S AU Williams, JL Tuerk, PW Acierno, R AF Williams, Joah L. Tuerk, Peter W. Acierno, Ron BE Tuerk, PW Shore, P TI Common Elements of the Expert Consensus Guidelines for Clinical Videoconferencing SO CLINICAL VIDEOCONFERENCING IN TELEHEALTH: PROGRAM DEVELOPMENT AND PRACTICE SE Behavioral Telehealth LA English DT Article; Book Chapter AB Purpose This chapter identifies common elements of various expert consensus guidelines for clinical videoconferencing (CV) services. We broadly conceptualize common elements as shared recommendations or themes addressed in the majority of published organizational guidelines (in this case, as identified in at least five of the nine major sets of national-level guidelines). Practice recommendations are discussed in the context of these common elements, specific guidelines are highlighted that represent the shared intention of common themes, and basic core requirements of CV programming are synthesized. We close the chapter by discussing notable variability among the guidelines pertaining to specific issues. Context Several professional organizations and agencies have published guides addressing the clinical, technical, and administrative standards applicable to CV-based health services. This information is useful for clinic managers and clinicians attempting to integrate CV into their practice in that these guidelines offer practical strategies for developing safe, patient-centered programs. Yet, a large amount of content related to expert consensus guidelines is available and not all guidelines are agreed on or pertinent to specific contexts. Accordingly, care is taken to represent commonalities of the various guidelines in order to provide a brief synopsis of the core recommendations considered to be essential across a majority of contexts. It is expected that managers and clinicians developing CV programming might use this information as a quick-reference base to begin considering CV procedures and policies, and then judge the merits of additional components from individual guidelines based on local programming needs and circumstances. Tools The chapter identifies and provides links to the expert consensus guidelines relevant to CV practice. Summary checklists of core similarities in the guidelines are provided related to CV technical considerations, physical set-up at the provider-and patient-end, clinical and administrative responsibilities, and specific provider behaviors that facilitate successful CV programming. Differences between the guidelines are also highlighted. While efforts have been taken in this volume to minimize the repetition of similar information presented across chapters, the current chapter represents somewhat of a departure from that rule given the overarching content matter. Accordingly, please note that most of the information summarized here is surveyed in much greater detail by the individually themed chapters. C1 [Williams, Joah L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Tuerk, Peter W.] Vet Hlth Adm, Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Acierno, Ron] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. RP Williams, JL (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA. EM wiljoah@musc.edu; Tuerk@musc.edu NR 11 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2199-8604 BN 978-3-319-08765-8; 978-3-319-08764-1 J9 BEHAV TELEHEALTH PY 2015 BP 55 EP 67 DI 10.1007/978-3-319-08765-8_3 D2 10.1007/978-3-319-08765-8 PG 13 WC Psychology, Clinical; Health Care Sciences & Services; Health Policy & Services; Medical Informatics; Psychiatry SC Psychology; Health Care Sciences & Services; Medical Informatics; Psychiatry GA BF0EP UT WOS:000378626900005 ER PT S AU Hilty, DM Yellowlees, PM Tuerk, PW Nasatir-Hilty, SEH Shoemaker, EZ Johnston, B Pato, MT AF Hilty, Donald M. Yellowlees, Peter M. Tuerk, Peter W. Nasatir-Hilty, Sarah E. H. Shoemaker, Erica Z. Johnston, Barb Pato, Michele T. BE Tuerk, PW Shore, P TI Program Evaluation and Modification: Supporting Pragmatic Data-Driven Clinical Videoconferencing (CV) Services SO CLINICAL VIDEOCONFERENCING IN TELEHEALTH: PROGRAM DEVELOPMENT AND PRACTICE SE Behavioral Telehealth LA English DT Article; Book Chapter ID POSTTRAUMATIC-STRESS-DISORDER; PRIMARY-CARE; TELEPSYCHIATRY CONSULTATION; TELEMENTAL HEALTH; DEVELOPMENTAL-DISABILITIES; ADOLESCENT TELEPSYCHIATRY; PATIENT SATISFACTION; MANAGEMENT-SYSTEM; RANDOMIZED-TRIAL; DEPRESSION AB Purpose This chapter discusses the prioritization of desired outcomes and ongoing program evaluation in the provision of clinical videoconferencing (CV) services. It provides an overall organizing framework to consider program evaluation from the very early stages of planning. Emphasis is placed on crafting evaluation fitted to specific needs and available resources. Context Understanding the fundamentals of program evaluation is necessary for clinical managers, clinicians, and telehealth experts because the processes of sound evaluation are essential for goal-directed programming and innovation with new CV services. Program evaluation may require a fundamental shift in philosophy-from measuring what happens with services, to planning for specific desired outcomes, and then gathering support for and designing services around those specific outcomes-in advance. The foundation for high-quality evaluation is a program with organizational support and an interdisciplinary team that shares responsibilities for overlapped roles. Tools The chapter provides a number of concrete tools to assist in planning for and implementing CV program evaluation. Included is a list of team-based resources which should be evaluated during the program development stage; a list of team qualities that can be planned for and assessed; examples for identifying multidimensional goals and alignment of goals across facilities; resources highlighting types of cost analyses; a list of cost-related outcomes and questions relevant to CV programming; a list of satisfaction-related CV outcomes for patients, providers, and support staff; examples of relevant process-oriented evaluation measures; a table organizing different types of reference groups for comparing CV program outcomes; and a list of program evaluation do's and don'ts. References and resources for information are also provided for further review. C1 [Hilty, Donald M.; Shoemaker, Erica Z.; Pato, Michele T.] USC, Keck Sch Med, Dept Psychiat, Los Angeles, CA USA. [Yellowlees, Peter M.] Hlth Informat Fellowship Program UC Davis, UC Davis Dept Psychiat, Sacramento, CA USA. [Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Tuerk, Peter W.] Vet Hlth Adm, Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Nasatir-Hilty, Sarah E. H.] USC, Keck Sch Med, Dept Psychiat, Los Angeles, CA USA. [Johnston, Barb] HealthLinkNow, Sacramento, CA USA. RP Hilty, DM (reprint author), USC, Keck Sch Med, Dept Psychiat, Los Angeles, CA USA. EM hilty@usc.edu NR 53 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2199-8604 BN 978-3-319-08765-8; 978-3-319-08764-1 J9 BEHAV TELEHEALTH PY 2015 BP 105 EP 130 DI 10.1007/978-3-319-08765-8_6 D2 10.1007/978-3-319-08765-8 PG 26 WC Psychology, Clinical; Health Care Sciences & Services; Health Policy & Services; Medical Informatics; Psychiatry SC Psychology; Health Care Sciences & Services; Medical Informatics; Psychiatry GA BF0EP UT WOS:000378626900008 ER PT S AU Shore, P Lu, M AF Shore, Peter Lu, Mary BE Tuerk, PW Shore, P TI Patient Safety Planning and Emergency Management SO CLINICAL VIDEOCONFERENCING IN TELEHEALTH: PROGRAM DEVELOPMENT AND PRACTICE SE Behavioral Telehealth LA English DT Article; Book Chapter AB Purpose This chapter provides practice guidelines and resources for patient risk evaluation and emergency response when providing clinical videoconferencing (CV) services to clinic-based and nonclinic-based settings. It contains information regarding provider preparation for both behavioral and medical emergencies. Additionally, this chapter provides information regarding the identification of suitable patients for CV services. Context This chapter is useful for clinicians because although behavioral and medical emergencies in mental health settings have been addressed in the literature for decades, guidelines for handling emergencies via CV are somewhat new. Providers offering or preparing to offer CV services must necessarily attend to the specifics of risk evaluation and emergency response protocols in CV settings. Tools This chapter provides an overview of available recommendations regarding emergency planning and response in CV settings, identifies specific procedures for selecting suitable patients and for conducting emergency planning prior to and during treatment for both clinic-based and nonclinic-based settings. This chapter also includes the following tools in the appendices: Pre-treatment checklists, pre-session checklists, emergency planning templates, clinical note template for documenting emergency plans, the Assessment for Suitability Home-Based Telemental Health (ASH-25)-a suicide risk assessment tool, and a list of additional resources related to chapter topics. C1 [Shore, Peter; Lu, Mary] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Shore, Peter] Dept Vet Affairs, VA NW Hlth Network VISN 20, Portland, OR USA. [Lu, Mary] Portland VA Med Ctr, Dept Vet Affairs, Portland, OR USA. RP Shore, P (reprint author), Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. EM shore@ohsu.edu NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2199-8604 BN 978-3-319-08765-8; 978-3-319-08764-1 J9 BEHAV TELEHEALTH PY 2015 BP 167 EP 201 DI 10.1007/978-3-319-08765-8_8 D2 10.1007/978-3-319-08765-8 PG 35 WC Psychology, Clinical; Health Care Sciences & Services; Health Policy & Services; Medical Informatics; Psychiatry SC Psychology; Health Care Sciences & Services; Medical Informatics; Psychiatry GA BF0EP UT WOS:000378626900010 ER PT S AU Lozano, BE Birks, AH Kloezeman, K Cha, N Morland, LA Tuerk, PW AF Lozano, Brian E. Birks, Anna Hynes Kloezeman, Karen Cha, Nancy Morland, Leslie A. Tuerk, Peter W. BE Tuerk, PW Shore, P TI Therapeutic Alliance in Clinical Videoconferencing: Optimizing the Communication Context SO CLINICAL VIDEOCONFERENCING IN TELEHEALTH: PROGRAM DEVELOPMENT AND PRACTICE SE Behavioral Telehealth LA English DT Article; Book Chapter ID FACE-TO-FACE; POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIOR THERAPY; OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE-UTILIZATION; PATIENT-SATISFACTION; TELEMENTAL HEALTH; WORKING ALLIANCE; TELECOMMUNICATIONS TECHNOLOGY AB Purpose This chapter addresses methods to establish or bolster therapeutic alliance with patients engaged in clinical videoconferencing (CV). The chapter will present a brief summary of the existing literature on therapeutic alliance to support a discussion of how therapeutic alliance may be impacted when conducting CV services. The chapter will also denote modifications to standard clinical behaviors which have been linked to strong therapeutic alliance in CV settings. Context The information is helpful for clinicians and managers because alliance has been demonstrated to be related to clinical outcomes for behavioral treatments. Stakeholders and clinicians new to CV contexts often question the ability of CV services to facilitate appropriate levels of alliance; accordingly, it is helpful to have access to a quick-reference summary in order to provide support for programming. Moreover, though the scientific literature base regarding CV provides broad evidence that appropriate alliance is most often achieved via CV, it is still important to convey specialized nuances of alliance in CV contexts. The authors have logged over 10,000 clinical hours via CV and have amassed a significant amount of highly-specific procedural knowledge regarding at-distance relationship building through practical experience and trial and error. Accordingly, the information is helpful in preventing those new to CV from starting from scratch or recreating the wheel when considering alliance in CV contexts. Tools The chapter provides the following tools: a brief review of the literature regarding therapeutic alliance and the effects of alliance on clinical outcomes in CV contexts, a list of psychotherapy contexts in which CV treatment has been associated with strong or adequate patient-provider alliance, a separate list of more general health care domains in which CV treatment has been associated with strong or adequate patient-provider satisfaction, a list of clinical techniques and clinician attributes that have been empirically associated with alliance, a more targeted list of suggestions to bolster alliance in CV contexts, a provider-oriented checklist of tasks to complete before initial CV sessions to safeguard alliance, a provider-oriented checklist of tasks to complete during initial CV sessions to safeguard alliance, and a checklist of procedures for when patients express concerns regarding receiving treatment via CV modalities. Finally, links to resources documenting technical and physical configurations to support alliance in CV contexts are provided, as are sample videos of provider/patient interactions over the modality. C1 [Lozano, Brian E.; Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. [Lozano, Brian E.; Tuerk, Peter W.] Vet Hlth Adm, Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Birks, Anna Hynes] Vet Hlth Adm, Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Kloezeman, Karen; Cha, Nancy; Morland, Leslie A.] Dept Vet Affairs Pacific Isl Healthcare Syst, Natl Ctr PTSD, Pacific Isl Div, Honolulu, HI USA. RP Lozano, BE (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM Lozano@musc.edu; anna.birks@va.gov NR 90 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2199-8604 BN 978-3-319-08765-8; 978-3-319-08764-1 J9 BEHAV TELEHEALTH PY 2015 BP 221 EP 251 DI 10.1007/978-3-319-08765-8_10 D2 10.1007/978-3-319-08765-8 PG 31 WC Psychology, Clinical; Health Care Sciences & Services; Health Policy & Services; Medical Informatics; Psychiatry SC Psychology; Health Care Sciences & Services; Medical Informatics; Psychiatry GA BF0EP UT WOS:000378626900012 ER PT J AU Zhou, YC Hu, XY Tang, ZM Ahn, AC AF Zhou, Yichao Hu, Xiyuan Tang, Zhenmin Ahn, Andrew C. GP IEEE TI Denoising and Baseline Correction of ECG Signals using Sparse Representation SO 2015 IEEE INTERNATIONAL WORKSHOP ON SIGNAL PROCESSING SYSTEMS (SIPS 2015) LA English DT Proceedings Paper CT IEEE International Workshop on Signal Processing Systems (SiPS) CY OCT 14-16, 2015 CL Hangzhou, PEOPLES R CHINA SP IEEE DE sparse representation; adaptive signal separation; ECG denoising; baseline wandering correction ID SEPARATION AB Removing noise and other artifacts in the electrocardiogram (ECG) is a critical preprocessing step for further heart disease analysis and diagnosis. In this paper, we propose a sparse representation based ECG signal denoising and baseline wandering (BW) correction algorithm. Unlike the traditional filtering-based methods, like Fourier or Wavelet transform, which use fixed basis, the proposed algorithm models the ECG signal as superposition of few inner structures plus additive random noise, while those structures can be learned from the input signal or a training set. Using those learned inner structures and their properties, we can accurately approximate the original ECG signal and remove noise and other artifacts like baseline wandering. To demonstrate the robustness and efficacy of the proposed algorithm, we compare it to several state-of-the-art algorithms through both simulated and real-life ECG recordings. C1 [Zhou, Yichao; Tang, Zhenmin] Nanjing Univ Sci & Technol, Sch Comp Sci, Nanjing 210094, Jiangsu, Peoples R China. [Hu, Xiyuan] Chinese Acad Sci, Inst Automat, Beijing 100190, Peoples R China. [Ahn, Andrew C.] Harvard Med Sch, MGH, BIDMC, Boston, MA 02215 USA. RP Zhou, YC (reprint author), Nanjing Univ Sci & Technol, Sch Comp Sci, Nanjing 210094, Jiangsu, Peoples R China. EM wingegg313@126.com; xiyuan.hu@ia.ac.cn; aahn1@mgh.harvard.edu NR 16 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-9604-2 PY 2015 PG 6 WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BF0KD UT WOS:000378944000024 ER PT S AU Wadley, VG McClure, LA Warnock, DG Lassen-Greene, CL Hopkin, RJ Laney, DA Clarke, VM Tamura, MK Howard, G Sims, K AF Wadley, Virginia G. McClure, Leslie A. Warnock, David G. Lassen-Greene, Caroline L. Hopkin, Robert J. Laney, Dawn A. Clarke, Virginia M. Tamura, Manjula Kurella Howard, George Sims, Katherine BE Zschocke, J Baumgartner, M Morava, E Patterson, M Rahman, S Peters, V TI Cognitive Function in Adults Aging with Fabry Disease: A Case-Control Feasibility Study Using Telephone-Based Assessments SO JIMD REPORTS, VOL 18 SE JIMD Reports LA English DT Article; Book Chapter ID QUALITY-OF-LIFE; NEUROPSYCHOLOGICAL ASSESSMENT; ALZHEIMERS-DISEASE; IMPAIRMENT; STROKE; METAANALYSIS; PERFORMANCE; DEPRESSION; SYMPTOMS; REGISTRY AB We examined the feasibility of recruiting US adults >= 45 years old with Fabry disease (FD) for telephone assessments of cognitive functioning. A case-control design matched each FD participant on age, sex, race, and education to four participants from a population-based study. Fifty-four participants with FD age 46-72 years were matched to 216 controls. Standardized cognitive assessments, quality of life (QOL), and medical histories were obtained by phone, supplemented by objective indices of comorbidities. Normalized scores on six cognitive tasks were calculated. On the individual tasks, scores on list recall and semantic fluency were significantly lower among FD participants (p-values < 0.05), while scores on the other four tasks did not differ. After averaging each participant's normalized scores to form a cognitive composite, we examined group differences in composite scores, before and after adjusting for multiple covariates using generalized estimating equations. The composite scores of FD cases were marginally lower than controls before covariate adjustments (p = 0.08). QOL and mental health variables substantially attenuated this finding (p = 0.75), highlighting the influence of these factors on cognition in FD. Additional adjustment for cardiovascular comorbidities, kidney function, and stroke had negligible impact, despite higher prevalence in the FD sample. Telephone-based cognitive assessment methods are feasible among adults with FD, affording access to a geographically dispersed sample. Although decrements in discrete cognitive domains were observed, the overall cognitive function of older adults with FD was equivalent to that of well-matched controls before and after accounting for multiple confounding variables. C1 [Wadley, Virginia G.] Univ Alabama Birmingham, Dept Med, Div Gerontol Geriatr & Palliat Care, CH19 218T,1720 2nd Ave So, Birmingham, AL 35294 USA. [McClure, Leslie A.; Howard, George] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Warnock, David G.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [Lassen-Greene, Caroline L.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA. [Hopkin, Robert J.] Univ Cincinnati, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Hopkin, Robert J.] STAR Lysosomal Dis Ctr, Div Human Genet, Cincinnati, OH USA. [Laney, Dawn A.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [Clarke, Virginia M.; Sims, Katherine] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Tamura, Manjula Kurella] Vet Affairs Palo Alto Hlth Care Syst, Geriatr Res & Educ Clin Ctr, Palo Alto, CA USA. RP Wadley, VG (reprint author), Univ Alabama Birmingham, Dept Med, Div Gerontol Geriatr & Palliat Care, CH19 218T,1720 2nd Ave So, Birmingham, AL 35294 USA. EM vwadley@uab.edu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU NIA NIH HHS [P30 AG022838]; NINDS NIH HHS [U01 NS041588] NR 28 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2192-8304 BN 978-3-662-44863-2; 978-3-662-44862-5 J9 JIMD REP PY 2015 VL 18 BP 41 EP 50 DI 10.1007/8904_2014_346 D2 10.1007/978-3-662-44863-2 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity SC Endocrinology & Metabolism; Genetics & Heredity GA BE8SK UT WOS:000376981500005 PM 25567791 ER PT J AU Olson, CK Kutner, L AF Olson, C. K. Kutner, L. TI VIEWPOINTS AND FLASHPOINTS IN THE STUDY OF VIDEO GAME VIOLENCE AND AGGRESSION SO PSYCHOLOGY-JOURNAL OF THE HIGHER SCHOOL OF ECONOMICS LA English DT Article DE video games; media violence; aggression; computer games; research bias ID MEDIA VIOLENCE; PROSOCIAL BEHAVIOR; UNITED-STATES; COMPETITION; EASTERN; PLAY AB Researchers from different backgrounds have approached the topic of violent video games and aggression with varying assumptions, methods, and goals. Researchers from an experimental psychology orientation seek to test theories under controlled conditions, and assume that all children are at risk of harm from acting out violence during gameplay. They champion policies to reduce youth exposure to violent game content. Researchers from applied fields such as public health, clinical psychology and criminology assume that video game effects (negative or positive) will vary by child, circumstance and content, and seek to identify high-risk patterns via studies in real-world settings. These different lenses illuminate ongoing disagreements about the relationship, if any, between violent video games and harmful aggressive behaviors. Some disagreements could be mitigated through greater clarity in definitions and methods. For example, confusion arises when researchers fail to clearly define "aggression"; treat aggressive thoughts, feelings, and behaviors as part of a continuum; or view aggression as equivalent to harmful intent or violence. Studies suggest that media violence researchers, like all humans, tend to disproportionately seek out and value evidence that supports their point of view. Actively searching for common ground, and welcoming new researchers from a variety of disciplines, may help move the field forward. C1 [Olson, C. K.; Kutner, L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mental Hlth & Media, Boston, MA USA. RP Olson, CK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mental Hlth & Media, Boston, MA USA. EM ckolson@post.harvard.edu; lkutner@stanford.edu NR 42 TC 0 Z9 0 U1 4 U2 4 PU NATL RES UNIV HIGHER EDUCATION PI MOSCOW PA NATL RES UNIV HIGHER EDUCATION, MOSCOW, 00000, RUSSIA SN 1813-8918 J9 PSYCHOL-J HIGH SCH E JI Psychol.-J. High. Sch. Econ. PY 2015 VL 12 IS 1 BP 13 EP 28 PG 16 WC Psychology, Multidisciplinary SC Psychology GA DP6LA UT WOS:000378607400002 ER PT S AU Guonason, J Mehta, DD Quatieri, TF AF Guonason, Jon Mehta, Daryush D. Quatieri, Thomas F. GP IEEE TI EVALUATION OF SPEECH INVERSE FILTERING TECHNIQUES USING A PHYSIOLOGICALLY BASED SYNTHESIZER SO 2015 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING (ICASSP) SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT 40th IEEE International Conference on Acoustics, Speech, and Signal Processing (ICASSP) CY APR 19-24, 2014 CL Brisbane, AUSTRALIA SP IEEE, Inst Elect & Elect Engineers Signal Proc Soc DE Glottal inverse filtering; glottal flow; glottal closure instant detection; speech signal processing; acoustics ID SPEAKER IDENTIFICATION; FREQUENCY ESTIMATION; LINEAR PREDICTION; VOICE PRODUCTION; GLOTTAL FLOW; WAVE-FORM; PARAMETERIZATION; SIGNALS; MODEL AB Glottal inverse filtering methods are designed to derive a glottal flow waveform from a speech signal. In this paper, we evaluate and compare such methods using a speech synthesizer that simulates voice production in a physiologically-based manner that includes complexities such as nonlinear source-tract coupling. Five inverse filtering techniques are evaluated on 90 synthesized speech waveforms generated by setting six vowel configurations, three glottal models, and five fundamental frequencies. Using normalized mean square error as the primary performance metric of the estimated glottal flow derivative, results show that the accuracy of all methods depends on the configuration of the vocal tract, glottis and the fundamental frequency. Averaged over these conditions, the closed phase covariance and one weighted covariance algorithm yield lower error rates (0.41 +/- 0.2) than iterative and adaptive inverse filtering (0.49 +/- 0.1) and complex cepstrum decomposition (0.76 +/- 0.1). C1 [Guonason, Jon] Reykjavik Univ, Ctr Anal & Design Intelligent Agents, Menntavegur 1, Reykjavik, Iceland. [Mehta, Daryush D.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Mehta, Daryush D.; Quatieri, Thomas F.] MIT Lincoln Lab, Lexington, MA USA. RP Guonason, J (reprint author), Reykjavik Univ, Ctr Anal & Design Intelligent Agents, Menntavegur 1, Reykjavik, Iceland. EM jg@ru.is; mehta.daryush@mgh.harvard.edu; quatieri@ll.mn.edu NR 30 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4673-6997-8 J9 INT CONF ACOUST SPEE PY 2015 BP 4245 EP 4249 PG 5 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BE1SM UT WOS:000368452404077 ER PT J AU Charidimou, A Martinez-Ramirez, S Shoamanesh, A Oliveira, J Frosch, M Vashkevich, A Ayres, A Rosand, J Gurol, ME Greenberg, SM Viswanathan, A AF Charidimou, A. Martinez-Ramirez, S. Shoamanesh, A. Oliveira-Filho, J. Frosch, M. Vashkevich, A. Ayres, A. Rosand, J. Gurol, M. E. Greenberg, S. M. Viswanathan, A. TI Sporadic cerebral amyloid angiopathy with and without intracerebral haemorrhage: evidence for distinct disease phenotypes SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract CT 24th European Stroke Conference CY MAY 13-15, 2015 CL Vienna, AUSTRIA C1 [Charidimou, A.; Martinez-Ramirez, S.; Shoamanesh, A.; Oliveira-Filho, J.; Vashkevich, A.; Ayres, A.; Rosand, J.; Gurol, M. E.; Greenberg, S. M.; Viswanathan, A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Frosch, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2015 VL 39 SU 2 BP 158 EP 158 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DM0HD UT WOS:000376023400216 ER PT S AU Guo, T Lovell, NH Tsai, D Twyford, P Fried, S Morley, JW Suaning, GJ Dokos, S AF Guo, Tianruo Lovell, Nigel H. Tsai, David Twyford, Perry Fried, Shelley Morley, John W. Suaning, Gregg J. Dokos, Socrates GP IEEE TI Optimizing Retinal Ganglion Cell Responses to High-Frequency Electrical Stimulation Strategies for Preferential Neuronal Excitation SO 2015 7TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 7th Annual International IEEE EMBS Conference on Neural Engineering (NER) CY APR 22-24, 2015 CL Montpellier, FRANCE SP IEEE, EMBS ID TIGER SALAMANDER RETINA; MECHANISMS; SIMULATION AB A retinal ganglion cell (RGC) model based on accurate biophysics and detailed representations of cell morphologies was used to understand how these cells respond to electrical stimulation over a wide range of frequencies, spanning 50-2000 pulses per second (PPS). Our modeling results and associated in vitro data both suggest the usefulness of high stimulation frequency in effectively modulating the activity of RGCs. This model can be used for optimizing varied extracellular stimulus profiles, and to assist in the design of sophisticated stimulation strategies for clinical visual neuroprostheses. C1 [Guo, Tianruo; Lovell, Nigel H.; Tsai, David; Suaning, Gregg J.; Dokos, Socrates] UNSW Australia, Grad Sch Biomed Engn, Sydney, NSW 2052, Australia. [Tsai, David] Columbia Univ, Howard Hughes Med Inst, Biol Sci & Bioelect Syst Lab, Elect Engn, New York, NY 10032 USA. [Morley, John W.] Univ Western Sydney, Sch Med, Penrith, NSW 1797, Australia. [Twyford, Perry; Fried, Shelley] VA Boston Healthcare Syst, Boston, MA USA. [Twyford, Perry; Fried, Shelley] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Twyford, Perry; Fried, Shelley] Harvard Univ, Sch Med, Boston, MA USA. RP Lovell, NH (reprint author), UNSW Australia, Grad Sch Biomed Engn, Sydney, NSW 2052, Australia. EM n.lovell@unsw.edu.au NR 18 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4673-6389-1 J9 I IEEE EMBS C NEUR E PY 2015 BP 252 EP 255 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BE9FT UT WOS:000377414600063 ER PT S AU Im, M Fried, SI AF Im, Maesoon Fried, Shelley I. GP IEEE TI Spatial Properties of Network-Mediated Response of Retinal Ganglion Cells to Electric Stimulation SO 2015 7TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 7th Annual International IEEE EMBS Conference on Neural Engineering (NER) CY APR 22-24, 2015 CL Montpellier, FRANCE SP IEEE, EMBS ID PROSTHESIS; ARRAY AB Retinal prosthetics consistently demonstrate the ability to restore limited visual perception to those blinded from outer retinal degenerative diseases. However, the performance of retinal implants is highly inconsistent and high-density arrays have proven only marginally better than much sparser ones suggesting that improving the overall quality of elicited vision may require more than just a high density electrode array. Existing devices are also implanted subretinally and epiretinally raising the possibility that electrode location also contributes to percept quality. Here, we compared the responses to stimulation from subretinal and epiretinal electrodes in the same cell. Use of a 4x4 subretinal electrode array allowed us to also compare responses to different numbers of electrodes activated simultaneously. Surprisingly, responses showed minimal dependence of both the electrode position (epiretinal vs. subretinal) as well as on electrode size (one vs. up to nine electrodes). However, when charge density considerations are implemented, such as those that are necessary during clinical use, the responses arising from smaller electrodes were less effective. This finding may help to explain the inconsistency between theoretical visual acuity and achievement in clinical testing with the high density implanted arrays. C1 [Im, Maesoon; Fried, Shelley I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Fried, Shelley I.] VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Fried, SI (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. EM im.maesoon@mgh.harvard.edu; fried.shelley@mgh.harvard.edu NR 22 TC 0 Z9 0 U1 1 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4673-6389-1 J9 I IEEE EMBS C NEUR E PY 2015 BP 256 EP 259 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BE9FT UT WOS:000377414600064 ER PT S AU Lee, SW Fried, SI AF Lee, Seung Woo Fried, Shelley I. GP IEEE TI Magnetic control of cortical pyramidal neuron activity using a micro-coil SO 2015 7TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 7th Annual International IEEE EMBS Conference on Neural Engineering (NER) CY APR 22-24, 2015 CL Montpellier, FRANCE SP IEEE, EMBS ID BRAIN-STIMULATION AB Transcranial magnetic stimulation (TMS) is a noninvasive method that modulates neural activity in the central nervous systems. It has been widely used both to study basic structure and function of the nervous system as well as to treat neurological diseases, i.e. clinical depression. However, ongoing advancements have been hampered by a lack of understanding as to the mechanisms by which TMS modulates neural activity. Here, we report responses from two distinct types of cortical pyramidal neurons to magnetic stimulation arising from a sub-millimeter coil. Cell attached patch clamps were used to record neural activity of layer 5 pyramidal neurons of the prefrontal cortex (PFC) in the in vitro mouse brain slice preparation. We found that both types of L5 pyramidal neurons were strongly excited by 10 Hz repetitive simulation when the coil was positioned on distal apical dendrites (i.e. layer 1-4). However, the excitation switched into strong inhibition when the coil was positioned close to the soma (i.e. close to layer 5) for one type of neuron, but not for the other type. These results suggest that responses of the L5 pyramidal neurons of the PFC are heterogeneous depending on the cell-type, and further, that this type of approach may be useful for studying the cellular level mechanisms underlying repetitive TMS. C1 [Lee, Seung Woo; Fried, Shelley I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, MGH Thier 415,50 Blossom St, Boston, MA 02114 USA. [Fried, Shelley I.] Boston VA Healthcare Syst Rehabil Res & Dev, Boston, MA 01230 USA. RP Fried, SI (reprint author), Boston VA Healthcare Syst Rehabil Res & Dev, Boston, MA 01230 USA. EM Lee.Seungwoo@mgh.harvard.edu; Fried.Shelley@mgh.harvard.edu NR 12 TC 0 Z9 0 U1 2 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4673-6389-1 J9 I IEEE EMBS C NEUR E PY 2015 BP 268 EP 271 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BE9FT UT WOS:000377414600067 ER PT J AU Ahluwalia, N Mugo, BM Feghali-Bostwick, C Pardo, A Selman, M Lagares, D Tager, AM AF Ahluwalia, N. Mugo, B. M. Feghali-Bostwick, C. Pardo, A. Selman, M. Lagares, D. Tager, A. M. TI Lung Injury Induces Non-Cell-Autonomous Fibroblast Invasion During The Development Of Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Ahluwalia, N.; Mugo, B. M.; Lagares, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Feghali-Bostwick, C.] Med Univ S Carolina, Charleston, SC 29425 USA. [Pardo, A.] Univ Nacl Autonoma Mexico, Mexico City 04510, DF, Mexico. [Selman, M.] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. [Tager, A. M.] Massachusetts Gen Hosp, Charlestown, MA USA. EM nahluwalia1@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5334 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807153 ER PT J AU Ahluwalia, S Mularski, RA Lendon, J Prendergast, T Neville, TH Lorenz, K AF Ahluwalia, S. Mularski, R. A. Lendon, J. Prendergast, T. Neville, T. H. Lorenz, K. TI Improving Icu Family Meetings: Do The Experts Agree With The Evidence? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Ahluwalia, S.] RAND Corp, Santa Monica, CA USA. [Mularski, R. A.] Kaiser Permanente Northwest, Portland, OR USA. [Lendon, J.; Lorenz, K.] VA Greater Los Angeles, Los Angeles, CA USA. [Lendon, J.; Lorenz, K.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Prendergast, T.] Portland VA Med Ctr, Portland, CA USA. [Prendergast, T.] Oregon Hlth & Sci Univ, Portland, CA USA. [Neville, T. H.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800006 ER PT J AU Akgun, KM Tate, JP Womack, J Brown, TT Leaf, DA Crystal, S Justice, AC Crothers, KA Oursler, KK AF Akgun, K. M. Tate, J. P. Womack, J. Brown, T. T. Leaf, D. A. Crystal, S. Justice, A. C. Crothers, K. A. Oursler, K. K. TI Is Chronic Obstructive Pulmonary Disease (COPD) An Independent Risk Factor For An Adapted Frailty-Related Phenotype In Hiv-Infected Compared With Uninfected Persons? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Akgun, K. M.; Tate, J. P.; Womack, J.; Justice, A. C.] VA Connecticut, West Haven, CT USA. [Akgun, K. M.; Tate, J. P.; Justice, A. C.] Yale Univ, Sch Med, West Haven, CT 06516 USA. [Womack, J.] Yale Univ, Sch Nursing, West Haven, CT USA. [Brown, T. T.] Johns Hopkins Univ, Baltimore, MD USA. [Leaf, D. A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Leaf, D. A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Crystal, S.] Rutgers State Univ, New Brunswick, NJ 08903 USA. [Crothers, K. A.] Univ Washington, Sch Med, Seattle, WA USA. [Oursler, K. K.] Salem VA Med Ctr, Salem, VA USA. [Oursler, K. K.] Univ Maryland, SOM, Salem, VA USA. EM kathleen.akgun@yale.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4713 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806148 ER PT J AU Alladina, J Hibbert, KA Harris, RS Thompson, BT Januzzi, JL Bajwa, E AF Alladina, J. Hibbert, K. A. Harris, R. S. Thompson, B. T. Januzzi, J. L. Bajwa, E. TI Prognostic Value Of Biomarkers In Weaning Mechanical Ventilation In Patients With Acute Respiratory Distress Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Alladina, J.; Hibbert, K. A.; Harris, R. S.; Thompson, B. T.; Januzzi, J. L.; Bajwa, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, R. S.; Januzzi, J. L.; Bajwa, E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6254 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582808489 ER PT J AU Au, DH Berger, D Carvalho, PG Collins, M Goodman, RB Gunnink, E McDowell, J Moss, BR Nelson, K Plumley, R Reinke, LF Weppner, W Woo, D Feemster, LC AF Au, D. H. Berger, D. Carvalho, P. G. Collins, M. Goodman, R. B. Gunnink, E. McDowell, J. Moss, B. R. Nelson, K. Plumley, R. Reinke, L. F. Weppner, W. Woo, D. Feemster, L. C. TI COPD Hospital Readmissions Penalites: Do Patients Discharged With COPD Diagnoses Have COPD? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Au, D. H.; Berger, D.; Collins, M.; Goodman, R. B.; Gunnink, E.; McDowell, J.; Moss, B. R.; Nelson, K.; Plumley, R.; Reinke, L. F.; Woo, D.; Feemster, L. C.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Carvalho, P. G.; Weppner, W.] Boise VA Med Ctr, Boise, ID USA. EM margaret.collins@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6478 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582808556 ER PT J AU Bai, X Shang, S Henao-Tamayo, M Basaraba, R Ovrutsky, A Matsuda, J Takeda, K Chan, M Dakhama, A Kinney, W Trostel, J Bai, A Achcar, R Hartney, J Kim, SH Dinarello, C Orme, I Ordway, DJ Chan, ED AF Bai, X. Shang, S. Henao-Tamayo, M. Basaraba, R. Ovrutsky, A. Matsuda, J. Takeda, K. Chan, M. Dakhama, A. Kinney, W. Trostel, J. Bai, A. Achcar, R. Hartney, J. Kim, S. -H. Dinarello, C. Orme, I. Ordway, D. J. Chan, E. D. TI Human Il-32 Expression Protects Mice Against A Hypervirulent Strain Of Mycobacterium Tuberculosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Bai, X.; Ovrutsky, A.; Matsuda, J.; Takeda, K.; Chan, M.; Dakhama, A.; Kinney, W.; Trostel, J.; Bai, A.; Achcar, R.; Hartney, J.; Kim, S. -H.] Natl Jewish Hlth, Denver, CO USA. [Shang, S.; Henao-Tamayo, M.; Basaraba, R.; Orme, I.; Ordway, D. J.] Colorado State Univ, Ft Collins, CO 80523 USA. [Dinarello, C.] Univ Colorado, Aurora, CO USA. [Chan, E. D.] Denver VAMC, Denver, CO USA. RI Shang, Shaobin/K-5669-2015; Henao-Tamayo, Marcela/D-8189-2017 OI Shang, Shaobin/0000-0003-4407-1911; Henao-Tamayo, Marcela/0000-0002-4249-9650 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3249 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803524 ER PT J AU Bann, M Lacy, M Ash, S Swenson, E AF Bann, M. Lacy, M. Ash, S. Swenson, E. TI Non-Invasive Total Hemoglobin Measurement: Can A Finger Probe Replace A Blood Draw? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Bann, M.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Lacy, M.] Univ New Mexico, Albuquerque, NM 87131 USA. [Ash, S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Swenson, E.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1654 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582801053 ER PT J AU Beane, J Mazzili, S Tassinari, A Geshalter, Y Mascaux, C Liu, G Zhang, S Liu, H Alexandrov, Y Reid, M Merrick, D Lam, S Lenburg, M Spira, A AF Beane, J. Mazzili, S. Tassinari, A. Geshalter, Y. Mascaux, C. Liu, G. Zhang, S. Liu, H. Alexandrov, Y. Reid, M. Merrick, D. Lam, S. Lenburg, M. Spira, A. TI Airway Gene-Expression Alterations Associated With Premalignancy: New Paradigms For Lung Cancer Chemoprevention SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Beane, J.; Mazzili, S.; Tassinari, A.; Geshalter, Y.; Liu, G.; Zhang, S.; Liu, H.; Alexandrov, Y.; Lenburg, M.; Spira, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Beane, J.; Mascaux, C.] Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. [Reid, M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Merrick, D.] Denver VA Med Ctr, Denver, CO USA. [Lam, S.] BC Canc Agcy, Vancouver, BC, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5158 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806592 ER PT J AU Beitler, JR Majumdar, R Hubmayr, RD Malhotra, A Thompson, BT Owens, RL Loring, SH Talmor, DS AF Beitler, J. R. Majumdar, R. Hubmayr, R. D. Malhotra, A. Thompson, B. T. Owens, R. L. Loring, S. H. Talmor, D. S. TI Relative Inspiratory Capacity Predicts Lung Stress In Acute Respiratory Distress Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Beitler, J. R.; Majumdar, R.; Malhotra, A.; Owens, R. L.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Beitler, J. R.; Hubmayr, R. D.] Mayo Clin, Rochester, MN USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Loring, S. H.; Talmor, D. S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3645 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804295 ER PT J AU Beitler, JR Malhotra, A Sands, SA Owens, RL Thompson, BT Loring, SH Talmor, DS AF Beitler, J. R. Malhotra, A. Sands, S. A. Owens, R. L. Thompson, B. T. Loring, S. H. Talmor, D. S. TI Occult High Tidal Volumes From Breath Stacking Dyssynchrony Occur Commonly During Low Tidal Volume Ventilation For Ards SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Beitler, J. R.; Malhotra, A.; Owens, R. L.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Sands, S. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Loring, S. H.; Talmor, D. S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3896 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804563 ER PT J AU Betancourt, J Patel, A Jun, D Lulla, A Patel, K Oh, SS AF Betancourt, J. Patel, A. Jun, D. Lulla, A. Patel, K. Oh, S. S. TI Clozapine-Induced Cardiovascular Collapse SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Betancourt, J.; Oh, S. S.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Betancourt, J.; Oh, S. S.] West Los Angeles VA Med Ctr, Los Angeles, CA USA. [Patel, A.; Jun, D.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Lulla, A.; Patel, K.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM jaimebetancourt@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3178 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803453 ER PT J AU Bhatt, SP Soler, X Wang, X Murray, S Allen, T Anzueto, A Beaty, TH Black-Shinn, JL Bon, J Boriek, AM Casaburi, R Cordova, FC Criner, GJ DeMeo, DL Diaz, AA Dransfield, MT Estepar, RS Everett, DC Foreman, MG Galban, CJ Hanania, NA Hokanson, JE Hoffman, EA Jensen, RL Kazerooni, EA Kim, V Kinney, GL Lan, C Li, D Lynch, DA Make, BJ Martinez, FJ McEvoy, C Parker, MM Parulekar, AD Porszasz, J Pratte, K Al Qaisi, MA Ramsdell, JW Ross, BD Rossiter, HB Sharafkhaneh, A Van Beek, EJ Sitek, A Steiner, RM Wan, ES Strand, MJ Washko, GR Wells, JM Wendt, CH Wise, RA Yen, A Silverman, EK Crapo, J Bowler, RP Han, MK AF Bhatt, S. P. Soler, X. Wang, X. Murray, S. Allen, T. Anzueto, A. Beaty, T. H. Black-Shinn, J. L. Bon, J. Boriek, A. M. Casaburi, R. Cordova, F. C. Criner, G. J. DeMeo, D. L. Diaz, A. A. Dransfield, M. T. Estepar, R. S. Everett, D. C. Foreman, M. G. Galban, C. J. Hanania, N. A. Hokanson, J. E. Hoffman, E. A. Jensen, R. L. Kazerooni, E. A. Kim, V. Kinney, G. L. Lan, C. Li, D. Lynch, D. A. Make, B. J. Martinez, F. J. McEvoy, C. Parker, M. M. Parulekar, A. D. Porszasz, J. Pratte, K. Al Qaisi, M. A. Ramsdell, J. W. Ross, B. D. Rossiter, H. B. Sharafkhaneh, A. Van Beek, E. J. Sitek, A. Steiner, R. M. Wan, E. S. Strand, M. J. Washko, G. R. Wells, J. M. Wendt, C. H. Wise, R. A. Yen, A. Silverman, E. K. Crapo, J. Bowler, R. P. Han, M. K. TI Predictors Of Lung Function Decline In Smokers In COPDgene Phase 2 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Bhatt, S. P.; Dransfield, M. T.] Univ Alabama Birmingham, Birmingham, AL USA. [Soler, X.] Univ Calif San Diego, San Diego, CA 92103 USA. [Wang, X.; Murray, S.; Galban, C. J.; Kazerooni, E. A.; Ross, B. D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Allen, T.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Beaty, T. H.] Johns Hopkins Univ, Baltimore, MD USA. [Black-Shinn, J. L.] Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO USA. [Bon, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Boriek, A. M.; Parulekar, A. D.; Sharafkhaneh, A.] Baylor Coll Med, Houston, TX 77030 USA. [Casaburi, R.] Harbor UCLA Med Ctr, Torrance, CA USA. [Cordova, F. C.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Criner, G. J.; Kim, V.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [DeMeo, D. L.; Wan, E. S.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Diaz, A. A.; Estepar, R. S.; Strand, M. J.; Washko, G. R.; Silverman, E. K.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Everett, D. C.; Lynch, D. A.; Make, B. J.; Al Qaisi, M. A.; Crapo, J.; Bowler, R. P.] Natl Jewish Hlth, Denver, CO USA. [Foreman, M. G.] Morehouse Sch Med, Atlanta, Afghanistan. [Hanania, N. A.] Baylor Coll Med, Asthma Clin Res Ctr, Houston, TX 77030 USA. [Hokanson, J. E.] Univ Colorado, Denver, DC USA. [Hoffman, E. A.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Jensen, R. L.] Univ Utah, Salt Lake City, UT USA. [Kinney, G. L.] Colorado Sch Publ Hlth, Aurora, CO USA. [Lan, C.] Michael E DeBakey VAMC, Houston, TX USA. [Li, D.] David Geffen Sch Med, Torrance, CA USA. [Martinez, F. J.] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA. [McEvoy, C.] HealthPartners Sleep Ctr, Maplewood, MN USA. [Parker, M. M.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Porszasz, J.; Rossiter, H. B.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Pratte, K.] Univ Colorado, Aurora, CO USA. [Ramsdell, J. W.] Univ Calif San Diego, San Diego, CA 92103 USA. [Van Beek, E. J.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Sitek, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Steiner, R. M.] Temple Univ, Philadelphia, PA 19122 USA. [Wells, J. M.] UAB, Birmingham, AL USA. [Wendt, C. H.] Univ Minnesota, Minneapolis, MN USA. [Wise, R. A.] Johns Hopkins Med Ctr, Baltimore, MD USA. [Yen, A.] UCSD Med Ctr, San Diego, CA USA. [Han, M. K.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. EM spbhatt@uab.edu NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2433 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802287 ER PT J AU Black, KE Bain, G Berdyshev, E Gorshkova, I Probst, CK Fontaine, BA Knipe, RS Lagares, D Ahluwalia, N Castelino, F Shea, BS Natarajan, V Tager, AM AF Black, K. E. Bain, G. Berdyshev, E. Gorshkova, I. Probst, C. K. Fontaine, B. A. Knipe, R. S. Lagares, D. Ahluwalia, N. Castelino, F. Shea, B. S. Natarajan, V. Tager, A. M. TI Autotaxin-Independent Lysophosphatidic Acid (lpa) Generation In Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Black, K. E.; Probst, C. K.; Fontaine, B. A.; Knipe, R. S.; Lagares, D.; Ahluwalia, N.; Castelino, F.; Tager, A. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bain, G.] Pharmakea Therapeut, San Diego, CA USA. [Berdyshev, E.; Gorshkova, I.; Natarajan, V.] Univ Illinois, Chicago, IL USA. [Shea, B. S.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. EM kblack1@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2358 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802152 ER PT J AU Cattano, D Brayanov, J George, E AF Cattano, D. Brayanov, J. George, E. TI Respiratory Volume Variability Prior To Opioid Administration As An Indicator For Opioid-Induced Respiratory Depression SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Cattano, D.] Univ Texas Houston, Sch Med, Houston, TX USA. [Cattano, D.; Brayanov, J.] MIT, Boston, MA USA. [George, E.] Massachusets Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1081 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800082 ER PT J AU Chan, ED Rizque, M Langston, L AF Chan, E. D. Rizque, M. Langston, L. TI Unusual Cause Of Upper Gastrointestinal Bleeding In An Immunocompromised Patient SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Chan, E. D.] Natl Jewish Hlth, Denver, CO USA. [Chan, E. D.; Rizque, M.; Langston, L.] Denver VAMC, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4645 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806080 ER PT J AU Chan, ED Frazer-Abel, A Woroch, E Bohn, M Giclas, P Bishokarma, P AF Chan, E. D. Frazer-Abel, A. Woroch, E. Bohn, M. Giclas, P. Bishokarma, P. TI Heparin Significantly Restores C1 Esterase Inhibitor (c1-Inh) Activity Ex Vivo In Patients With Hereditary Angioedema SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Chan, E. D.; Frazer-Abel, A.; Woroch, E.; Giclas, P.; Bishokarma, P.] Natl Jewish Hlth, Denver, CO USA. [Bohn, M.] Denver VAMC, Denver, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4208 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582805267 ER PT J AU Chan, ED Oberley-Deegan, R Bai, A Ovrutsky, A Kinney, W Weaver, M Honda, J Pott, G Shapiro, L Bai, X AF Chan, E. D. Oberley-Deegan, R. Bai, A. Ovrutsky, A. Kinney, W. Weaver, M. Honda, J. Pott, G. Shapiro, L. Bai, X. TI Curcumin Enhances Macrophage Control Of Mycobacterium Tuberculosis Infection SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Chan, E. D.; Oberley-Deegan, R.; Bai, A.; Ovrutsky, A.; Kinney, W.; Weaver, M.; Honda, J.; Bai, X.] Natl Jewish Hlth, Denver, CO USA. [Chan, E. D.; Pott, G.; Shapiro, L.] Denver VAMC, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3250 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803525 ER PT J AU Channick, RN Joish, VN Platt, D Xia, F Teal, S Orden, M Satler, C Tapson, V AF Channick, R. N. Joish, V. N. Platt, D. Xia, F. Teal, S. Orden, M. Satler, C. Tapson, V. TI Occurrence Of Pulmonary Hypertension Following Newly Diagnosed Pulmonary Embolism Patients In The United States SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Channick, R. N.] Massachsetts Gen Hosp, Boston, MA USA. [Joish, V. N.; Platt, D.; Xia, F.; Satler, C.] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Teal, S.; Orden, M.] Bayer Pharma AG, Berlin, Germany. [Tapson, V.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. EM david.platt@bayer.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4831 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806265 ER PT J AU Chin, KM Channick, R Frey, A Gaine, S Ghofrani, HA Hoeper, M Lang, I McIaughlin, V Preiss, R Simonneau, G Sitbon, O Stefani, M Tapson, V Galie, N Rubin, LJ AF Chin, K. M. Channick, R. Frey, A. Gaine, S. Ghofrani, H. -A. Hoeper, M. Lang, I. McIaughlin, V. Preiss, R. Simonneau, G. Sitbon, O. Stefani, M. Tapson, V. Galie, N. Rubin, L. J. TI Selexipag Prolongs The Time To Morbidity/mortality Events In Key Subgroup Populations: Results From Griphon, A Randomized Controlled Study In Pulmonary Arterial Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Chin, K. M.] UT Southwestern, Dallas, TX USA. [Channick, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Frey, A.; Preiss, R.; Stefani, M.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Gaine, S.] Mater Misericordiae Univ Hosp, Dublin, Ireland. [Ghofrani, H. -A.] Univ Giessen, D-35390 Giessen, Germany. [Ghofrani, H. -A.] Marburg Lung Ctr, Giessen, Germany. [Hoeper, M.] Hannover Med Sch, Hannover, Germany. [Lang, I.] Med Univ Vienna, Vienna, Austria. [McIaughlin, V.] Univ Michigan, Ann Arbor, MI 48109 USA. [Simonneau, G.; Sitbon, O.] Univ Paris Sud, Hop Univ Bicetre, F-94275 Le Kremlin Bicetre, France. [Tapson, V.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Galie, N.] Univ Bologna, Ist Malattie Apparato Cardiovasc, Bologna, Italy. [Rubin, L. J.] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2199 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582801591 ER PT J AU Costa, LD Harris, RS Venegas, JG Melo, MFV Musch, G Correia, JA Winkler, T AF Costa, L. Degani Harris, R. S. Venegas, J. G. Melo, M. F. Vidal Musch, G. Correia, J. A. Winkler, T. TI Reliability Of Estimates Of Lung Perfusion Heterogeneity Using Positron Emission Tomography (pet) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Costa, L. Degani] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Harris, R. S.; Venegas, J. G.; Melo, M. F. Vidal; Musch, G.; Correia, J. A.; Winkler, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, R. S.; Melo, M. F. Vidal; Winkler, T.] Harvard Univ, Sch Med, Boston, MA USA. EM luizadeg@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3510 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804160 ER PT J AU Delcroix, M Channick, RN Galie, N Ghofrani, HA Jansa, P Mehta, S Perchenet, L Pulido, T Sastry, B Sitbon, O Souza, R Torbicki, A Verweij, P Rubin, LJ Simonneau, G AF Delcroix, M. Channick, R. N. Galie, N. Ghofrani, H. A. Jansa, P. Mehta, S. Perchenet, L. Pulido, T. Sastry, B. Sitbon, O. Souza, R. Torbicki, A. Verweij, P. Rubin, L. J. Simonneau, G. TI Prognostic Indicators Of Long-Term Outcome In Pulmonary Arterial Hypertension: Results From The Seraphin Event-Driven Morbidity/mortality Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Delcroix, M.] Univ Hosp Gasthuisberg, Leuven, Belgium. [Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Galie, N.] Bologna Univ Hosp, Bologna, Italy. [Ghofrani, H. A.] Univ Giessen, D-35390 Giessen, Germany. [Ghofrani, H. A.] Marburg Lung Ctr UGMLC, Giessen, Germany. [Ghofrani, H. A.] Imperial Coll London London UK, Giessen, Germany. [Jansa, P.] Charles Univ Prague, Prague, Czech Republic. [Mehta, S.] Univ Western Ontario, Victoria Hosp, London Hlth Sci Ctr, London, ON, Canada. [Perchenet, L.; Verweij, P.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Pulido, T.] Ignacio Chavez Natl Heart Inst, Mexico City, DF, Mexico. [Sastry, B.] CARE Hosp, Hyderabad, Andhra Pradesh, India. [Sitbon, O.; Simonneau, G.] Univ Paris Sud, Hop Bicetre, AP HP, Serv Pneumol,Lab Excellence Rech Med & Innovat Th, F-94275 Le Kremlin Bicetre, France. [Sitbon, O.; Simonneau, G.] INSERM, U 999, F-94275 Le Kremlin Bicetre, France. [Souza, R.] Univ Sao Paulo, Sch Med, Heart Inst, Sao Paulo, Brazil. [Torbicki, A.] ECZ Otwock, Med Ctr Postgrad Educ, Otwock, Poland. [Rubin, L. J.] Univ Calif San Diego, San Diego Med Sch, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5503 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807364 ER PT J AU Desogere, PA Tapias-Vargas, L Rietz, TA Rotile, N Blasi, F Day, H Fuchs, B Lanuti, M Caravan, P AF Desogere, P. A. Tapias-Vargas, L. Rietz, T. A. Rotile, N. Blasi, F. Day, H. Fuchs, B. Lanuti, M. Caravan, P. TI Optimization Of A Collagen-Targeted Positron Emission Tomography (pet) Probe For Molecular Imaging Of Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc ID CONTRAST AGENT; MICE; MRI C1 [Desogere, P. A.; Rietz, T. A.; Rotile, N.; Blasi, F.; Day, H.; Caravan, P.] Massachusettes Gen Hosp, Boston, MA USA. [Desogere, P. A.; Tapias-Vargas, L.; Fuchs, B.; Lanuti, M.] Massachussets Gen Hosp, Boston, MA USA. EM desogere@nmr.mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4968 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806402 ER PT J AU DuBrock, HM LeVarge, BL Rodriguez-Lopez, J Channick, RN AF DuBrock, H. M. LeVarge, B. L. Rodriguez-Lopez, J. Channick, R. N. TI Is The Current Model For End Stage Liver Disease (meld) Exception Scoring System Appropriate For Patients With Portopulmonary Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [DuBrock, H. M.; LeVarge, B. L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rodriguez-Lopez, J.; Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hdubrock@bidmc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5516 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807377 ER PT J AU DuBrock, HM LeVarge, BL Curry, MP Rodriguez-Lopez, J Channick, RN Karumanchi, SA AF DuBrock, H. M. LeVarge, B. L. Curry, M. P. Rodriguez-Lopez, J. Channick, R. N. Karumanchi, S. A. TI The Role Of Endothelin-1 In The Pathogenesis Of Portopulmonary Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [DuBrock, H. M.; LeVarge, B. L.; Curry, M. P.; Karumanchi, S. A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rodriguez-Lopez, J.; Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hdubrock@bidmc.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4830 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806264 ER PT J AU Dumas, O Mansbach, JM Hasegawa, K Sullivan, AF Piedra, PA Camargo, CA AF Dumas, O. Mansbach, J. M. Hasegawa, K. Sullivan, A. F. Piedra, P. A. Camargo, C. A. TI A Clustering Approach To Identify Bronchiolitis Profiles Among Children Hospitalized With Bronchiolitis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Dumas, O.; Sullivan, A. F.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Dumas, O.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Mansbach, J. M.] Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp, Boston, MA USA. [Hasegawa, K.; Camargo, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Piedra, P. A.] Baylor Coll Med, Dept Mol Virol, Houston, TX 77030 USA. [Piedra, P. A.] Baylor Coll Med, Dept Microbiol, Houston, TX 77030 USA. [Piedra, P. A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. EM orianne.dumas@channing.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2632 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802485 ER PT J AU Dutta, J Winkler, T Carvalho, AR Spieth, PM Guldner, A El Fakhri, G De Abreu, MG Melo, MFV Li, Q AF Dutta, J. Winkler, T. Carvalho, A. R. Spieth, P. M. Guldner, A. El Fakhri, G. De Abreu, M. G. Melo, M. F. Vidal Li, Q. TI Validation Of High-Resolution Computation Of Lung Strain Distribution During Mechanical Ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Dutta, J.; Winkler, T.; El Fakhri, G.; Melo, M. F. Vidal; Li, Q.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winkler, T.; Spieth, P. M.] Univ Hosp Carl Gustav Carus, Dresden, Germany. [Spieth, P. M.; De Abreu, M. G.] Univ Hosp Dresden, Dresden, Germany. [Melo, M. F. Vidal] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1214 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800213 ER PT J AU Falcao, LR Wellman, TJ Winkler, T Capelozzi, VL Harris, RS Musch, G Venegas, JG Melo, MFV AF Falcao, L. R. Wellman, T. J. Winkler, T. Capelozzi, V. L. Harris, R. S. Musch, G. Venegas, J. G. Melo, M. F. Vidal TI Quantitative Assessment Of Neutrophilic Inflammation With Light And Electron Microscopy And Relationship With Pulmonary Kinetics Of 18f-Fluorodeoxyglucose In Early Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Wellman, T. J.] Boston Univ, Boston, MA 02215 USA. [Winkler, T.; Harris, R. S.; Musch, G.; Venegas, J. G.; Melo, M. F. Vidal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Capelozzi, V. L.] Univ Sao Paulo, Sao Paulo, Brazil. EM luizfernandofalcao@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4977 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806411 ER PT J AU Falcao, LR Winkler, T O'Neil, K Harris, RS Musch, G Venegas, JG Melo, MFV AF Falcao, L. R. Winkler, T. O'Neil, K. Harris, R. S. Musch, G. Venegas, J. G. Melo, M. F. Vidal TI Topographical Sources Of Ventilation Heterogeneity After Mild, Moderate, And Severe Acute Pulmonary Embolism SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Falcao, L. R.; Melo, M. F. Vidal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Falcao, L. R.; Winkler, T.; O'Neil, K.; Harris, R. S.; Musch, G.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, R. S.] Harvard Univ, Sch Med, Boston, MA USA. EM luizfernandofalcao@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4869 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806303 ER PT J AU Farhat, M Sultana, R Murray, M AF Farhat, M. Sultana, R. Murray, M. TI Large Scale Sequencing Of Genetic Determinants Of Drug Resistance In Mycobacterium Tuberculosis: Implications For Diagnostic Design SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Farhat, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sultana, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Murray, M.] Harvard Univ, Sch Publ Hlth, Sch Med, Boston, MA 02115 USA. EM mrfarhat@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2184 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582801576 ER PT J AU Fleehart, S Nguyen, HQ Fan, VS Hunter, C Chen, Z Reinke, LF AF Fleehart, S. Nguyen, H. Q. Fan, V. S. Hunter, C. Chen, Z. Reinke, L. F. TI The Effect Of Psychosocial Behavioral Therapy For Patients With COPD And Depression SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Fleehart, S.; Fan, V. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Nguyen, H. Q.; Hunter, C.; Chen, Z.] Univ Washington, Seattle, WA 98195 USA. [Reinke, L. F.] Dept Vet Affairs, Edmonds, WA USA. EM reinkl@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6395 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803352 ER PT J AU Fracchia, MS Cook, AL Hardy, S Hartnick, CJ AF Fracchia, M. S. Cook, A. L. Hardy, S. Hartnick, C. J. TI The Role Of Triple Endoscopy In The Diagnosis And Management Of Pediatric Patients With Chronic Cough: A Case Series SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Fracchia, M. S.; Cook, A. L.; Hardy, S.] Massachusetts Gen Hosp Children, Boston, MA USA. [Hartnick, C. J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2624 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802477 ER PT J AU Gaffin, JM Petty, CR Lai, PS Sheehan, WJ Baxi, S Coull, BA Gold, DR Koutrakis, P Phipatanakul, W AF Gaffin, J. M. Petty, C. R. Lai, P. S. Sheehan, W. J. Baxi, S. Coull, B. A. Gold, D. R. Koutrakis, P. Phipatanakul, W. TI Prediction Of Indoor Air Particulate Matter From Ambient Measures In The School Inner City Asthma Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Gaffin, J. M.; Petty, C. R.; Sheehan, W. J.; Baxi, S.; Phipatanakul, W.] Boston Childrens Hosp, Boston, MA USA. [Lai, P. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Coull, B. A.; Koutrakis, P.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gold, D. R.] Harvard Univ, Sch Med, Boston, MA USA. EM jonathan.gaffin@childrens.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3232 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803507 ER PT J AU Gaffney, AW Hang, JQ Lee, MS Su, L Zhang, FY Christiani, DC AF Gaffney, A. W. Hang, J. -Q. Lee, M. -S. Su, L. Zhang, F. -Y. Christiani, D. C. TI Socioeconomic Status And Lung Function In A Population-Based Study In Shanghai, China SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Gaffney, A. W.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hang, J. -Q.; Su, L.; Zhang, F. -Y.] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Lee, M. -S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. EM agaffney@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4691 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806126 ER PT J AU Gaffney, AW Hang, JQ Lee, MS Su, L Zhang, FY Christiani, DC AF Gaffney, A. W. Hang, J. -Q. Lee, M. -S. Su, L. Zhang, F. -Y. Christiani, D. C. TI A Population-Based Study Of Mode Of Commuting And Pulmonary Function In Shanghai, China SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Gaffney, A. W.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hang, J. -Q.; Su, L.; Zhang, F. -Y.] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Lee, M. -S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802090 ER PT J AU Garshick, E Grady, S Hart, JE Moy, ML Coull, B Schwartz, J Laden, F Koutrakis, P AF Garshick, E. Grady, S. Hart, J. E. Moy, M. L. Coull, B. Schwartz, J. Laden, F. Koutrakis, P. TI Indoor Air Pollution Exposures And Reduced Pulmonary Function In COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Garshick, E.; Grady, S.; Moy, M. L.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Hart, J. E.; Laden, F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Coull, B.; Schwartz, J.; Koutrakis, P.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4043 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582805102 ER PT J AU Gilpin, SE Charest, JM Tapias, LF Ren, X Wu, T Mathisen, DJ Ott, H AF Gilpin, S. E. Charest, J. M. Tapias, L. F. Ren, X. Wu, T. Mathisen, D. J. Ott, H. TI Extended Biomimetic Culture And Functional Bio-Assessment Of Recellularized Human Lungs SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Gilpin, S. E.; Charest, J. M.; Tapias, L. F.; Ren, X.; Wu, T.; Mathisen, D. J.; Ott, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sgilpin@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5342 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807161 ER PT J AU Greenblatt, EE Winkler, T Harris, RS Kelly, V Kone, M Katz, I Martin, AR Cailibotte, G Venegas, JG AF Greenblatt, E. E. Winkler, T. Harris, R. S. Kelly, V. Kone, M. Katz, I. Martin, A. R. Cailibotte, G. Venegas, J. G. TI What Causes Uneven Aerosol Deposition In The Lung? A Quantitative Imaging Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Greenblatt, E. E.; Winkler, T.; Kone, M.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenblatt, E. E.] MIT, Boston, MA USA. [Harris, R. S.; Kelly, V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Katz, I.; Cailibotte, G.] Air Liquide R&D, Jouy En Josas, France. [Martin, A. R.] Univ Alberta, Edmonton, AB, Canada. EM eeg@mit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1226 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800225 ER PT J AU Guldner, A Braune, A Ball, L Silva, PL Samary, CDS Huhle, R Becker, C Insorsi, A Rentzsch, I Oehme, L Andreeff, M Melo, MFV Winkler, T Pelosi, P Rocco, PRM Kotzerke, J De Abreu, MG AF Guldner, A. Braune, A. Ball, L. Silva, P. L. Samary, C. D. S. Huhle, R. Becker, C. Insorsi, A. Rentzsch, I. Oehme, L. Andreeff, M. Melo, M. F. Vidal Winkler, T. Pelosi, P. Rocco, P. R. M. Kotzerke, J. De Abreu, M. Gama TI Volutrauma Is Associated With Higher Lung [18f]fluorodeoxyglucose Uptake Than Atelectrauma At Comparable Tidal Volumes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Guldner, A.; Braune, A.; Ball, L.; Huhle, R.; Becker, C.; Rentzsch, I.; Kotzerke, J.; De Abreu, M. Gama] Univ Hosp Carl Gustav Carus, Dresden, Germany. [Silva, P. L.; Samary, C. D. S.; Rocco, P. R. M.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. [Insorsi, A.; Pelosi, P.] Univ Genoa, Genoa, Italy. [Oehme, L.; Andreeff, M.] Uniklinikum Carl Gustav Carus, Dresden, Germany. [Melo, M. F. Vidal; Winkler, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM andreas.gueldner@uniklinikum-dresden.de RI Ball, Lorenzo/K-7612-2016 OI Ball, Lorenzo/0000-0002-3876-4730 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2386 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802180 ER PT J AU Hardin, CC Rajendran, K Manomohan, G Tambe, D Husain, A Dodson, RB Myers, C Butler, JP Fredberg, JJ Birukov, KG Stenmark, KR Krishnan, R AF Hardin, C. C. Rajendran, K. Manomohan, G. Tambe, D. Husain, A. Dodson, R. B. Myers, C. Butler, J. P. Fredberg, J. J. Birukov, K. G. Stenmark, K. R. Krishnan, R. TI Il-6 Induces Potent Increases In Cell-Substrate Tractions And Cell-Cell Stress In Human Pulmonary Artery Endothelial Cell Monolayers SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Hardin, C. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rajendran, K.; Manomohan, G.; Husain, A.; Krishnan, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tambe, D.] Univ S Alabama, Mobile, AL 36688 USA. [Dodson, R. B.] Univ Colorado Denver, Anschutz Med Campus, Aurora, CO USA. [Myers, C.; Stenmark, K. R.] Univ Colorado, Aurora, CO USA. [Butler, J. P.; Fredberg, J. J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Fredberg, J. J.; Birukov, K. G.] Univ Chicago, Chicago, IL 60637 USA. EM chardin@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2659 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802511 ER PT J AU Hasegawa, K Bittner, JC Herrera, V Gabriel, S Camargo, CA AF Hasegawa, K. Bittner, J. C. Herrera, V. Gabriel, S. Camargo, C. A. TI Adults With Frequent Hospitalizations For Acute Asthma, 2012-2013 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Hasegawa, K.; Bittner, J. C.; Camargo, C. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herrera, V.; Gabriel, S.] Novartis Pharmaceut, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6271 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582808506 ER PT J AU Heckman, EJ Latourelle, J Gerszten, RE Dupuis, J O'Connor, GT AF Heckman, E. J. Latourelle, J. Gerszten, R. E. Dupuis, J. O'Connor, G. T. TI Metabolomics In Sleep Apnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Heckman, E. J.; O'Connor, G. T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Latourelle, J.; Dupuis, J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Gerszten, R. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM heckmaer@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2708 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802559 ER PT J AU Hibbert, KA Kassis, EB Thompson, BT Januzzi, JL Harris, RS Bajwa, E AF Hibbert, K. A. Kassis, E. Baedorf Thompson, B. T. Januzzi, J. L. Harris, R. S. Bajwa, E. TI Unintended Consequences: Elevated Troponin Levels In Ards Patients Receiving Albuterol SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Hibbert, K. A.; Kassis, E. Baedorf; Thompson, B. T.; Januzzi, J. L.; Harris, R. S.; Bajwa, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hibbert, K. A.; Kassis, E. Baedorf; Thompson, B. T.; Januzzi, J. L.; Harris, R. S.; Bajwa, E.] Harvard Univ, Sch Med, Boston, MA USA. EM kahibbert@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6255 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582808490 ER PT J AU Hibbert, KA Winkler, T Kelly, VJ Cosgrove, K Holland, C Melo, MFV Harris, RS Bajwa, E AF Hibbert, K. A. Winkler, T. Kelly, V. J. Cosgrove, K. Holland, C. Melo, M. F. Vidal Harris, R. S. Bajwa, E. TI Regional Aeration And Inflammation In Healthy Volunteers And Subjects With Ards And Heart Failure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Hibbert, K. A.; Winkler, T.; Kelly, V. J.; Cosgrove, K.; Holland, C.; Melo, M. F. Vidal; Harris, R. S.; Bajwa, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winkler, T.; Kelly, V. J.; Cosgrove, K.; Holland, C.; Melo, M. F. Vidal; Harris, R. S.; Bajwa, E.] Harvard Univ, Sch Med, Boston, MA USA. EM kahibbert@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3109 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803384 ER PT J AU Hsu, DJ North, C Brode, SK Celli, BR AF Hsu, D. J. North, C. Brode, S. K. Celli, B. R. TI Predictors Of Influenza Vaccination In Patients With Chronic Obstructive Pulmonary Disease: Analysis Of The 2012 Behavioral Risk Factors Surveillance System SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Hsu, D. J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [North, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brode, S. K.] Univ Toronto, Toronto, ON, Canada. [Celli, B. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM dhsu@bidmc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6170 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582808405 ER PT J AU Hug, C Christiani, DC Kapur, K Biswas, SK Hasan, MOSI Rodrigues, EG Islam, F Chin, K Mostofa, MG Quamruzzaman, Q Rahman, M Mazumdar, M AF Hug, C. Christiani, D. C. Kapur, K. Biswas, S. K. Hasan, M. O. S. Ibne Rodrigues, E. G. Islam, F. Chin, K. Mostofa, M. G. Quamruzzaman, Q. Rahman, M. Mazumdar, M. TI Arsenic-Related Cystic Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Hug, C.; Kapur, K.; Islam, F.; Chin, K.; Mazumdar, M.] Boston Childrens Hosp, Boston, MA USA. [Christiani, D. C.; Rodrigues, E. G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Biswas, S. K.] Bangabandhu Sheikh Mujib Med Univ, Dhaka, Bangladesh. [Hasan, M. O. S. Ibne; Mostofa, M. G.; Quamruzzaman, Q.; Rahman, M.] Dhaka Community Hosp, Dhaka, Bangladesh. EM christopher.hug@childrens.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3338 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803612 ER PT J AU Jiwani, AZ Maple, E Mahon, I Apgar, C Atwood, CW Battaile, JT Browning, R Garshick, E Goldstein, RH Keith, RL More, K Morris, MJ Parrish, JS Reid, M Vachani, A Gatsonis, C Elashoff, D Duan, F Dubinett, SM Lenburgh, M Massion, PP Remick, DG Wistuba, II Schnall, M Spira, A AF Jiwani, A. Z. Maple, E. Mahon, I. Apgar, C. Atwood, C. W. Battaile, J. T. Browning, R., Jr. Garshick, E. Goldstein, R. H. Keith, R. L. More, K. Morris, M. J. Parrish, J. S. Reid, M. Vachani, A. Gatsonis, C. Elashoff, D. Duan, F. Dubinett, S. M. Lenburgh, M. Massion, P. P. Remick, D. G. Wistuba, I. I. Schnall, M. Spira, A. CA DECAMP Consortium TI Detection And Validation Of Molecular Biomarkers For The Early Detection Of Lung Cancer Among Military And Veteran Populations: The Decamp Consortium SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Jiwani, A. Z.; Maple, E.; Lenburgh, M.; Remick, D. G.; Spira, A.] Boston Univ, Med Ctr, Boston, MA USA. [Mahon, I.; Apgar, C.; Schnall, M.] Amer Coll Radiol, Imaging Network, Philadelphia, PA USA. [Atwood, C. W.] Univ Pittsburgh, Pittsburgh, PA USA. [Battaile, J. T.] Univ Texas Southwestern, Dallas, TX USA. [Browning, R., Jr.] Walter Reed Naval Med Ctr, Bethesda, MD USA. [Garshick, E.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Goldstein, R. H.] VA Boston Healthcare Syst, Boston, MA USA. [Keith, R. L.] VA Eastern Colorado Healthcare Syst, Denver, CO USA. [More, K.] Portsmouth Naval Med Ctr, Portsmouth, VA USA. [Morris, M. J.] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. [Parrish, J. S.] Naval Med Ctr, San Diego, CA USA. [Reid, M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Vachani, A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Gatsonis, C.; Duan, F.] Brown Univ, Providence, RI 02912 USA. [Elashoff, D.; Dubinett, S. M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Massion, P. P.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Wistuba, I. I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1249 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800248 ER PT J AU Johansen, T Winkler, T Greenblatt, EE Kelly, VJ Harris, RS Venegas, JG AF Johansen, T. Winkler, T. Greenblatt, E. E. Kelly, V. J. Harris, R. S. Venegas, J. G. TI Mapping Local Oxygen And Co2 Transfer Rates In The Lung SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Johansen, T.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Winkler, T.; Greenblatt, E. E.; Kelly, V. J.; Harris, R. S.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenblatt, E. E.] MIT, Boston, MA USA. [Harris, R. S.] Harvard Univ, Sch Med, Boston, MA USA. EM troels.johansen@ki.au.dk NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2126 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582801525 ER PT J AU Jolley, SE Moss, M Needham, DM Caldwell, ES Morris, PE Miller, RR Ringwood, N Anders, MG Koo, K Parry, SM Gundel, S Hough, CL AF Jolley, S. E. Moss, M. Needham, D. M. Caldwell, E. S. Morris, P. E. Miller, R. R. Ringwood, N. Anders, M. G. Koo, K. Parry, S. M. Gundel, S. Hough, C. L. TI Point Prevalence Study Of Intensive Care Unit Mobility Across The Acute Respiratory Distress Syndrome Network SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Jolley, S. E.] Louisiana State Univ, Sch Med, New Orleans, LA USA. [Moss, M.] Univ Colorado Denver, Aurora, CO USA. [Needham, D. M.] Johns Hopkins Univ, Baltimore, MD USA. [Caldwell, E. S.] Univ Washington, Seattle, WA 98195 USA. [Morris, P. E.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Miller, R. R.] Univ Utah, Sch Med, Intermt Healthcare, Murray, UT USA. [Ringwood, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Anders, M. G.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Koo, K.] Swedish Hlth Serv, Seattle, WA USA. [Parry, S. M.] Univ Melbourne, Melbourne, Vic, Australia. [Gundel, S.; Hough, C. L.] Univ Washington, Seattle, WA 98195 USA. EM sjolle@lsuhsc.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6349 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802267 ER EF