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