FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Menendez, ME Loeffler, M Ring, D AF Menendez, Mariano E. Loeffler, Markus Ring, David TI Patient Satisfaction in an Outpatient Hand Surgery Office: A Comparison of English- and Spanish-Speaking Patients SO QUALITY MANAGEMENT IN HEALTH CARE LA English DT Article DE CG-CAHPS; English; language barriers; patient satisfaction; quality improvement; Spanish ID CARPAL-TUNNEL RELEASE; HEALTH-CARE PROVIDERS; DECISION-MAKING; LANGUAGE CONCORDANCE; DEPRESSIVE SYMPTOMS; CONSUMER ASSESSMENT; MEDICAL ENCOUNTERS; UNCONSCIOUS RACE; CENTERED CARE; HOSPITAL-CARE AB Background: As health care in the United States transitions from a fee-for-service to an outcomes-based environment, patient satisfaction is increasingly incentivized and publicly reported. Despite the continued growth of the Latino population and concomitant rise in the demand for health care, relatively little is known regarding patient satisfaction in Spanish speakers. We sought to compare patient satisfaction with hand surgery office visits between Spanish-and English-speaking patients. Methods: Directly after the office visit, 150 patients (75 English speakers and 75 Spanish speakers) completed a sociodemographic survey, an 11-point ordinal rating of pain intensity, and a survey of satisfaction with the encounter using items derived from the CG-CAHPS (Clinician and Group-Consumer Assessment of Healthcare Providers and Systems) survey. Multivariable regression modeling was used to identify factors associated with patient dissatisfaction. Results: Overall, 79% of Spanish-speaking patients were satisfied with the physician as compared with 91% of English speakers (P = .041). Compared with English-speaking patients, Spanish speakers were less likely to be satisfied with provider listening carefully (91% vs 100%, P = .007) and spending enough time with them (56% vs 93%, P < .001), as well as with waiting times (81% vs 96%, P = .005). There was no difference with regard to provider showing respect, clarity of communication, and explanation of what was done. Younger age and Spanish language were independent predictors of patient dissatisfaction. Conclusions: Spanish-speaking patients are less satisfied with the care provided in a hand surgery office. In light of the growing diversity of the US population and the fact that patient satisfaction is increasingly tied to reimbursement, additional research might identify potential areas of improvement from both the surgeon (eg, communication strategies, cultural competence) and patient (eg health literacy, expectations) perspectives. C1 [Menendez, Mariano E.; Loeffler, Markus; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Ste 2100,55 Fruit St, Boston, MA 02114 USA. EM memenendez@partners.org NR 47 TC 0 Z9 0 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1063-8628 EI 1550-5154 J9 QUAL MANAG HEALTH CA JI Qual. Manag. Health Care PD OCT-DEC PY 2015 VL 24 IS 4 BP 183 EP 189 DI 10.1097/QMH.0000000000000074 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DD5LN UT WOS:000369965300003 PM 26426319 ER PT J AU Knight, JB Schott, NJ Kentor, ML Williams, BA AF Knight, Joshua B. Schott, Nicholas J. Kentor, Michael L. Williams, Brian A. TI Neurotoxicity of common peripheral nerve block adjuvants SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Review DE buprenorphine; clonidine; dexamethasone; local anesthetics; midazolam ID BRACHIAL-PLEXUS BLOCK; ACTIVATED CATION CURRENT; POSTOPERATIVE ANALGESIA; BUPRENORPHINE; BUPIVACAINE; MIDAZOLAM; DEXMEDETOMIDINE; CLONIDINE; ROPIVACAINE; DEXAMETHASONE AB Purpose of review This review outlines the analgesic role of perineural adjuvants for local anesthetic nerve block injections, and evaluates current knowledge regarding whether adjuvants modulate the neurocytologic properties of local anesthetics. Recent findings Perineural adjuvant medications such as dexmedetomidine, clonidine, buprenorphine, dexamethasone, and midazolam play unique analgesic roles. The dosing of these medications to prevent neurotoxicity is characterized in various cellular and in-vivo models. Much of this mitigation may be via reducing the dose of local anesthetic used while achieving equal or superior analgesia. Dose-concentration animal models have shown no evidence of deleterious effects. Clinical observations regarding blocks with combined bupivacaine-clonidine-buprenorphine-dexamethasone have shown beneficial effects on block duration and rebound pain without long-term evidence of neurotoxicity. In-vitro and in-vivo studies of perineural clonidine and dexmedetomidine show attenuation of perineural inflammatory responses generated by local anesthetics. Summary Dexmedetomidine added as a peripheral nerve blockade adjuvant improves block duration without neurotoxic properties. The combined adjuvants clonidine, buprenorphine, and dexamethasone do not appear to alter local anesthetic neurotoxicity. Midazolam significantly increases local anesthetic neurotoxicity in vitro, but when combined with clonidine-buprenorphine-dexamethasone (sans local anesthetic) produces no in-vitro or in-vivo neurotoxicity. Further larger-species animal testing and human trials will be required to reinforce the clinical applicability of these findings. C1 [Knight, Joshua B.; Schott, Nicholas J.; Kentor, Michael L.] Univ Pittsburgh, Med Ctr, Dept Anesthesiol, Pittsburgh, PA 15213 USA. [Williams, Brian A.] Univ Pittsburgh, Sch Med, VA Pittsburgh Hlth Syst, Pittsburgh, PA 15213 USA. RP Knight, JB (reprint author), Educ Off, Dept Anesthesiol, Liliane S Kaufmann Bldg,3471 Fifth Ave,Suite 910, Pittsburgh, PA 15213 USA. EM knightjb@upmc.edu FU Department of Anesthesiology, University of Pittsburgh Medical Center; VA Pittsburgh Health System, Pittsburgh, Pennsylvania, USA FX This work was supported by the Department of Anesthesiology, University of Pittsburgh Medical Center (J.B.K., N.J.S., and M.L.K.), and by the VA Pittsburgh Health System (B.A.W.), Pittsburgh, Pennsylvania, USA. NR 28 TC 4 Z9 5 U1 5 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0952-7907 EI 1473-6500 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD OCT PY 2015 VL 28 IS 5 BP 598 EP 604 DI 10.1097/ACO.0000000000000222 PG 7 WC Anesthesiology SC Anesthesiology GA DC9CY UT WOS:000369519900018 PM 26207854 ER PT J AU Fuller, SC Donald, PJ AF Fuller, Scott C. Donald, Paul J. TI Evaluating risk factors and predicting complications in head and neck reconstructive surgery SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY LA English DT Review DE complications; microvascular; reconstruction; risk factors ID FREE-FLAP RECONSTRUCTION; CLEAN-CONTAMINATED HEAD; FREE-TISSUE TRANSFER; C-REACTIVE PROTEIN; MICROVASCULAR HEAD; PERIOPERATIVE COMPLICATIONS; CANCER SURGERY; DEFECTS; HYPERCOAGULABILITY; THERAPY AB Purpose of reviewComplications in head and neck reconstructive surgery can have devastating effects. There is a tremendous body of literature examining risk factors that may predict complications in this patient population, thereby minimizing or avoiding adverse outcomes.Recent findingsRotational thromboelastometry may provide a mechanism to predict coagulopathy in patients undergoing microvascular reconstruction. Surveillance of serum C-reactive protein levels may provide an additional tool for early intervention in wound complications Controversy persists in the literature regarding specific risk factors and associated perioperative complications.SummaryPerioperative medical and surgical complications are commonplace in the management of complex oncologic disease and attendant defect reconstructions. Potential risk factors have been examined exhaustively in the literature without a consensus being established. C1 [Fuller, Scott C.] US Dept Vet Affairs, Northern Calif Healthcare Syst, Div Otolaryngol, 10535 Hosp Way, Mather, CA 95655 USA. [Fuller, Scott C.; Donald, Paul J.] Univ Calif, Davis Med Ctr, Dept Otolaryngol, Sacramento, CA USA. RP Fuller, SC (reprint author), US Dept Vet Affairs, Northern Calif Healthcare Syst, Div Otolaryngol, 10535 Hosp Way, Mather, CA 95655 USA. EM scott.fuller@va.gov NR 40 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1068-9508 EI 1531-6998 J9 CURR OPIN OTOLARYNGO JI Curr. Opin. Otolaryngol. Head Neck Surg. PD OCT PY 2015 VL 23 IS 5 BP 415 EP 419 DI 10.1097/MOO.0000000000000192 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA DC7RB UT WOS:000369416800009 PM 26339973 ER PT J AU McCunney, RJ Mundt, KA Colby, WD Dobie, R Kaliski, K Blais, M AF McCunney, Robert J. Mundt, Kenneth A. Colby, W. David Dobie, Robert Kaliski, Kenneth Blais, Mark TI "Wind Turbines and Health: A Critical Review of the Scientific Literature'' WIND TURBINES AND HEALTH: AN INFORMED OPINION Response SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Letter ID QUALITY-OF-LIFE C1 [McCunney, Robert J.] MIT, 77 Massachusetts Ave,16-771, Cambridge, MA 02139 USA. [Mundt, Kenneth A.] Environ Int, Epidemiol, Amherst, MA USA. [Colby, W. David] Middlesex London Hlth Unit, Travel Immunizat Clin, London, ON, Canada. [Dobie, Robert] Dobie Associates, San Antonio, TX USA. [Kaliski, Kenneth] Resource Syst Grp, Environm Energy & Acoust, White River Jct, VT USA. [Blais, Mark] Massachusetts Gen Hosp, Psychol Evaluat & Res Lab, Boston, MA 02114 USA. RP McCunney, RJ (reprint author), MIT, 77 Massachusetts Ave,16-771, Cambridge, MA 02139 USA. EM mccunney@mit.edu NR 16 TC 1 Z9 1 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD OCT PY 2015 VL 57 IS 10 BP E133 EP E135 DI 10.1097/JOM.0000000000000559 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DD0UG UT WOS:000369634900005 PM 26461875 ER PT J AU Khalid, AN Ladha, KS Luong, AU Quraishi, SA AF Khalid, Ayesha N. Ladha, Karim S. Luong, Amber U. Quraishi, Sadeq A. TI Association of Vitamin D Status and Acute Rhinosinusitis Results From the United States National Health and Nutrition Examination Survey 2001-2006 SO MEDICINE LA English DT Article ID LOCALLY WEIGHTED REGRESSION; ANTIMICROBIAL PEPTIDES; EPITHELIAL-CELLS; NASAL POLYPOSIS; D DEFICIENCY; ADULTS; CATHELICIDIN; INFECTIONS; SINUSITIS; ANTIBIOTICS AB Although vitamin D status may be a modifiable risk factor for various respiratory ailments, limited data exists regarding its role in sinonasal infections. Our goal was to investigate the association of 25-hydroxyvitamin D (25OHD) levels with acute rhinosinusitis (ARS) in a large, nationally representative sample of non-institutionalized individuals from the United States.In this cross-sectional study of individuals 17 years from the National Health and Nutrition Examination Survey 2001-2006, we used multivariable regression analysis to investigate the association of 25OHD levels with ARS, while adjusting for season, demographics (age, sex, race, and poverty-to-income ratio), and clinical data (smoking, asthma, chronic obstructive pulmonary disease, diabetes mellitus, and neutropenia).A total of 3921 individuals were included in our analyses. Median 25OHD level was 22 (interquartile range 16-28) ng/mL. Overall, 15.8% (95% confidence interval [CI] 14.4-17.7) of participants reported ARS within the 24 hours leading up to their survey participation. After adjusting for season, demographics, and clinical data, 25OHD levels were associated with ARS (odds ratio 0.88, 95% CI 0.78-0.99 per 10ng/mL). When vitamin D status was dichotomized, 25OHD levels <20ng/mL were associated with 33% higher odds of ARS (odds ratio 1.33, 95% CI 1.03-1.72) compared with levels 20ng/mL.Our analyses suggest that 25OHD levels are inversely associated with ARS. Randomized, controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of sinonasal infections. C1 [Khalid, Ayesha N.] Cambridge Hosp, Dept Surg, Div Otolaryngol Head & Neck Surg, Cambridge, MA 02139 USA. [Khalid, Ayesha N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Khalid, Ayesha N.] Boston Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [Ladha, Karim S.; Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Ladha, Karim S.; Quraishi, Sadeq A.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. [Luong, Amber U.] Univ Texas Med Sch Houston, Dept Otorhinolaryngol Head & Neck Surg, Houston, TX USA. RP Khalid, AN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRJ 402, Boston, MA 02114 USA. EM squraishi@mgh.harvard.edu FU National Institutes of Health [UL1 TR000371, KL2 TR000370, L30TR001257]; GREER; ENTvantage; Intersect ENT; Amgen; Mallinckrodt FX A.U.L. is supported by the National Institutes of Health grants UL1 TR000371 and KL2 TR000370. S.A.Q. is supported by National Institutes of Health grant L30TR001257.; A.N.K. received speaker's fees from GREER. A.U.L. received consulting fees from GREER and ENTvantage, and industry research funding from Intersect ENT, Amgen, and Mallinckrodt. The other authors have no funding and conflicts of interest to disclose. NR 48 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD OCT PY 2015 VL 94 IS 40 AR e1447 DI 10.1097/MD.0000000000001447 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DC7MB UT WOS:000369403200001 PM 26447998 ER PT J AU Ni, JQ Fang, XT Zhong, WY Liu, N Wood, KB AF Ni, Jianqiang Fang, Xiutong Zhong, Weiye Liu, Ning Wood, Kirkham B. TI Anterior Lumbar Interbody Fusion for Degenerative Discogenic Low Back Pain Evaluation of L4-S1 Fusion SO MEDICINE LA English DT Article ID TOTAL DISC REPLACEMENT; VISUAL ANALOG SCALES; DISCOGRAPHY; CONTRAINDICATIONS; COHORT; TRIAL AB The treatment of degenerative discogenic pain is controversial, and anterior lumbar fusion for the treatment of degenerative discogenic low back pain has also been a controversial topic for over a generation.The aim of this systematic review was to evaluate the outcome of different anterior lumbar fusion levels for degenerative discogenic low back pain.In this study, we performed a clinical outcome subgroup analysis. The outcomes of 84 consecutive patients who underwent anterior lumbar interbody fusion from 2004 to 2009 were reviewed. The operative time, intraoperative blood loss, hospital stay, Oswestry Disability Index (ODI), visual analog scale (VAS) results, and complication rate were recorded separately.Medical indications were degenerative disc disease (73.8%), postdiscectomy disc disease (16.1%), and disc herniation (9.5%). Patients with severe spondylolysis or disc degeneration, with more than 3 or multilevel lesions, were excluded.The mean operative time was 124.510.9min (range 51-248min), the mean intraoperative blood loss was 242.1 +/- 27.7mL (range 50-2700mL), the mean hospital stay was 3.9 +/- 1.1 days (range 3-6 days), the mean preoperative VAS score was 7.5 +/- 1.4, and the mean preoperative ODI score was 60.0 +/- 5.7. At the 1-year follow-up, the mean postoperative VAS score was 3.3 +/- 1.3 and the mean postoperative ODI score was 13.6 +/- 3.4 (P<0.05). L4-L5 disc fusion led to better clinical results than 2-level L4-L5/L5-S1 disc fusion. Additionally, the 2-level fusion of L4-L5/L5-S1 had better clinical results than the L5-S1 disc fusion at both the 1 and 2-year postoperative follow-ups regarding the VAS score and the ODI score. The rate of complications was more frequent in the 2-level L4-L5/L5-S1 group (27.3%) (group C) than in the L4-L5 group (9.1%) (group A) and the L5-S1 group (12.5%) (group B). There was no difference between the L4-L5 group (9.1%) and the L5-S1 group (12.5%). A venous tear occurred during surgery and was successfully repaired in 6 of the 84 patients. Also, out of the 84 patients, 6 were found with pseudarthrosis during the follow-up, and these patients underwent a spinal fusion with instrumentation, with a posterior approach after a mean of 1 year. The complications secondary to the surgical approach were persistent abdominal pain (1/84, 1.2%) and wound dehiscence (1/84, 1.2%).Anterior lumbar interbody fusion for L4-L5 had better clinical results than the 2-segmental L4-L5/L5-S1 disc fusion, and the 2-segmental L4-L5/L5-S1 disc fusion had better clinical results than the L5-S1 disc fusion. Also, the 2-segmental L4-L5/L5-S1 disc fusion had a higher complication rate (27.3%), but there was no difference between the L4-L5 group (9.1%) and the L5-S1 group (12.5%). C1 [Ni, Jianqiang; Fang, Xiutong; Zhong, Weiye; Liu, Ning; Wood, Kirkham B.] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ni, Jianqiang] Yuhungding Hosp, Dept Orthoped, Qingdao, Shandong, Peoples R China. [Fang, Xiutong] Affiliated Beijing Capital Med Univ, Beijing ShiJiTan Hosp, Dept Orthoped, Beijing, Peoples R China. RP Ni, JQ (reprint author), Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM KBWOOD@mgh.harvard.edu NR 32 TC 1 Z9 1 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD OCT PY 2015 VL 94 IS 43 AR e1851 DI 10.1097/MD.0000000000001851 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DC9IS UT WOS:000369535500044 PM 26512594 ER PT J AU Manchikanti, L Atluri, S Kaye, AD Hirsch, JA AF Manchikanti, Laxmaiah Atluri, Sairam Kaye, Alan David Hirsch, Joshua A. TI Untitled SO SPINE LA English DT Letter ID INJECTIONS C1 [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Atluri, Sairam] Tri State Spine Care Inst, Cincinnati, OH USA. [Kaye, Alan David] LSU Hlth Sci Ctr, Dept Anesthesia, New Orleans, LA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. EM drlm@thepainmd.com; saiatluri@gmail.com; akaye@lsuhsc.edu; HIrsch@snisonline.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD OCT 1 PY 2015 VL 40 IS 19 BP E1071 EP E1071 DI 10.1097/BRS.0000000000001084 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DC4WE UT WOS:000369220200006 PM 26244407 ER PT J AU Jiang, YD Kacmarek, RM AF Jiang, Yandong Kacmarek, Robert M. TI Efficacy of Superimposed High-frequency Jet Ventilation Applied to Variable Degrees of Tracheal Stenosis One Step Forward to Optimized Patient Care SO ANESTHESIOLOGY LA English DT Editorial Material ID AIRWAY EXCHANGE CATHETER; COMPLICATIONS; SURGERY C1 [Jiang, Yandong] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. [Kacmarek, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA USA. RP Jiang, YD (reprint author), Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. EM yandong.jiang@vanderbilt.edu NR 13 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2015 VL 123 IS 4 BP 747 EP 749 DI 10.1097/ALN.0000000000000819 PG 3 WC Anesthesiology SC Anesthesiology GA DB7YW UT WOS:000368734600004 PM 26259138 ER PT J AU Wiener-Kronish, JP AF Wiener-Kronish, Jeanine P. TI Emery N. Brown, MD, Ph.D., Recipient of the 2015 Excellence in Research Award SO ANESTHESIOLOGY LA English DT Biographical-Item C1 [Wiener-Kronish, Jeanine P.] Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. RP Wiener-Kronish, JP (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2015 VL 123 IS 4 BP 759 EP 762 DI 10.1097/ALN.0000000000000816 PG 4 WC Anesthesiology SC Anesthesiology GA DB7YW UT WOS:000368734600005 ER PT J AU Purdon, PL Sampson, A Pavone, KJ Brown, EN AF Purdon, Patrick L. Sampson, Aaron Pavone, Kara J. Brown, Emery N. TI Clinical Electroencephalography for Anesthesiologists Part I: Background and Basic Signatures SO ANESTHESIOLOGY LA English DT Review ID REFRACTORY STATUS EPILEPTICUS; INDUCED ALPHA-RHYTHM; PATIENT STATE INDEX; CEREBRAL BLOOD-FLOW; NITROUS-OXIDE; GENERAL-ANESTHESIA; BURST-SUPPRESSION; BISPECTRAL INDEX; AGONIST DEXMEDETOMIDINE; INDUCED UNCONSCIOUSNESS AB The widely used electroencephalogram-based indices for depth-of-anesthesia monitoring assume that the same index value defines the same level of unconsciousness for all anesthetics. In contrast, we show that different anesthetics act at different molecular targets and neural circuits to produce distinct brain states that are readily visible in the electroencephalogram. We present a two-part review to educate anesthesiologists on use of the unprocessed electroencephalogram and its spectrogram to track the brain states of patients receiving anesthesia care. Here in part I, we review the biophysics of the electroencephalogram and the neurophysiology of the electroencephalogram signatures of three intravenous anesthetics: propofol, dexmedetomidine, and ketamine, and four inhaled anesthetics: sevoflurane, isoflurane, desflurane, and nitrous oxide. Later in part II, we discuss patient management using these electroencephalogram signatures. Use of these electroencephalogram signatures suggests a neurophysiologically based paradigm for brain state monitoring of patients receiving anesthesia care. C1 [Purdon, Patrick L.; Sampson, Aaron; Pavone, Kara J.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB 444, Boston, MA 02114 USA. [Purdon, Patrick L.; Brown, Emery N.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Brown, Emery N.] Inst Med Engn & Sci, Cambridge, MA USA. [Brown, Emery N.] Harvard MIT, Hlth Sci & Technol Program, Cambridge, MA USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Purdon, PL; Brown, EN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB 444, Boston, MA 02114 USA. EM patrickp@nmr.mgh.harvard.edu; enb@neurostat.mit.edu FU National Institutes of Health, Bethesda, Maryland, [DP1-OD003646, DP2-OD006454, TR01-GM104948]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts FX Supported by grants DP1-OD003646 (to Dr. Brown), DP2-OD006454 (to Dr. Purdon), and TR01-GM104948 (to Dr. Brown) from the National Institutes of Health, Bethesda, Maryland, and funds from the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. NR 134 TC 18 Z9 18 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2015 VL 123 IS 4 BP 937 EP 960 DI 10.1097/ALN.0000000000000841 PG 24 WC Anesthesiology SC Anesthesiology GA DB7YW UT WOS:000368734600024 PM 26275092 ER PT J AU Sharifpour, M Bittner, EA Dzik, WH AF Sharifpour, Milad Bittner, Edward A. Dzik, Walter H. TI Adding a New Piece to the Transfusion Puzzle in Oncologic Surgery Patients SO ANESTHESIOLOGY LA English DT Letter ID RANDOMIZED-CONTROLLED-TRIAL; BLOOD-TRANSFUSIONS; CANCER; REQUIREMENTS; OUTCOMES; RISK C1 [Sharifpour, Milad] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sharifpour, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM msharifpour@partners.org NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2015 VL 123 IS 4 BP 968 EP 969 DI 10.1097/ALN.0000000000000801 PG 3 WC Anesthesiology SC Anesthesiology GA DB7YW UT WOS:000368734600029 PM 26372129 ER PT J AU Vaala, SE Hood, KK Laffel, L Kumah-Crystal, YA Lybarger, CK Mulvaney, SA AF Vaala, Sarah E. Hood, Korey K. Laffel, Lori Kumah-Crystal, Yaa A. Lybarger, Cindy K. Mulvaney, Shelagh A. TI Use of Commonly Available Technologies for Diabetes Information and Self-Management Among Adolescents With Type 1 Diabetes and Their Parents: A Web-Based Survey Study SO INTERACTIVE JOURNAL OF MEDICAL RESEARCH LA English DT Article DE diabetes mellitus; Type 1; adolescent; technology; adoption; self-management; self-care ID ONLINE SOCIAL NETWORKING; GLYCEMIC CONTROL; METABOLIC-CONTROL; YOUTH; ADHERENCE; OUTCOMES; SUPPORT; COMMUNICATION; METAANALYSIS; INVOLVEMENT AB Background: For individuals with Type 1 diabetes (T1D), following a complicated daily medical regimen is critical to maintaining optimal health. Adolescents in particular struggle with regimen adherence. Commonly available technologies (eg, diabetes websites, apps) can provide diabetes-related support, yet little is known about how many adolescents with T1D use them, why they are used, or relationships between use and self-management. Objective: This study examined adolescent and parent use of 5 commonly available technologies for diabetes, including proportions who use each technology, frequency of use, and number of different technologies used for diabetes. Analyses also investigated the reasons adolescents reported for using or not using technologies for diabetes, and factors correlated with adolescents' technology use. Finally, this study examined relationships between the type and number of technologies adolescents use for diabetes and their self-management and glycemic control. Methods: Adolescents (12-17 years) and their parents (N= 174 pairs), recruited from a pediatric diabetes clinic (n= 134) and the Children with Diabetes community website (n= 40), participated in this Web-based survey study. Glycosylated hemoglobin (A1C) values were obtained from medical records for pediatric clinic patients. Adolescents reported their use of 5 commonly available technologies for diabetes (ie, social networking, diabetes websites, mobile diabetes apps, text messaging, and glucometer/ insulin pump software), reasons for use, and self-management behavior (Self-Care Inventory-Revised, SCI-R). Results: Most adolescents and parents used at least one of the 5 technologies for diabetes. Among adolescents, the most commonly used technology for diabetes was text messaging (53%), and the least commonly used was diabetes websites (25%). Most adolescents who used diabetes apps, text messaging, or pump/ glucometer software did so more frequently (>= 2 times per week), compared to social networking and website use (<= 1 time per week). The demographic, clinical, and parent-technology use factors related to adolescents' technology use varied by technology. Adolescents who used social networking, websites, or pump/ glucometer software for diabetes had better self-management behavior (SCI-R scores: beta=.18, P=.02; beta=.15, P=.046; beta=.15, P=. 04, respectively), as did those who used several technologies for diabetes (beta=.23, P=. 003). However, use of diabetes websites was related to poorer glycemic control (A1C: beta=.18, P=. 01). Conclusions: Adolescents with T1D may be drawn to different technologies for different purposes, as individual technologies likely offer differing forms of support for diabetes self-management (eg, tracking blood glucose or aiding problem solving).Findings suggest that technologies that are especially useful for adolescents' diabetes problem solving may be particularly beneficial for their self-management. Additional research should examine relationships between the nature of technology use and adolescents' T1D self-management over time. C1 [Vaala, Sarah E.; Mulvaney, Shelagh A.] Vanderbilt Univ, Sch Nursing, 461 21st Ave South, Nashville, TN 37240 USA. [Hood, Korey K.] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA. [Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kumah-Crystal, Yaa A.; Mulvaney, Shelagh A.] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA. [Kumah-Crystal, Yaa A.; Lybarger, Cindy K.; Mulvaney, Shelagh A.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. RP Mulvaney, SA (reprint author), Vanderbilt Univ, Sch Nursing, 461 21st Ave South, Nashville, TN 37240 USA. EM shelagh.mulvaney@vanderbilt.edu FU NCATS NIH HHS [UL1 TR000445]; NIDDK NIH HHS [DP3 DK097706, P30 DK092986] NR 39 TC 4 Z9 4 U1 7 U2 10 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1929-073X J9 INTERACT J MED RES JI Interact. J. Med. Res. PD OCT-DEC PY 2015 VL 4 IS 4 BP 34 EP 46 DI 10.2196/ijmr.4504 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DC2UK UT WOS:000369072500004 PM 26715191 ER PT J AU Vodopivec, I Rinehart, EM Griffin, GK Johncilla, ME Pecora, N Yokoe, DS Feske, SK Milner, DA Folkerth, RD AF Vodopivec, Ivana Rinehart, Elizabeth M. Griffin, Gabriel K. Johncilla, Melanie E. Pecora, Nicole Yokoe, Deborah S. Feske, Steven K. Milner, Danny A., Jr. Folkerth, Rebecca D. TI A Cluster of CNS Infections Due to B. cereus in the Setting of Acute Myeloid Leukemia: Neuropathology in 5 Patients SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Abscess; Bacillus cereus; CNS infection; Hemorrhage; Leukemia; Meningoencephalitis; Outbreak ID OF-THE-LITERATURE; BACILLUS-CEREUS; ANTIMICROBIAL AGENTS; MENINGITIS; ANTHRACIS; RANGE; PCR; THURINGIENSIS; PATHOGENESIS; MYCOIDES AB Bacillus cereus typically causes a self-limited foodborne gastrointestinal (GI) illness. Severe invasive infection occurs rarely, mainly among immunocompromised hosts. We describe a cluster of B. cereus infections among 5 patients with acute myeloid leukemia and chemotherapy-induced neutropenia. The initial case presented with occipital lobe abscess and was found on biopsy to have organisms consistent with Bacillus species. Within 1 week, a second patient died of fulminant brain swelling and hemorrhage. Neuropathologic autopsy and culture revealed B. cereus; hospital infection control and public health officials were notified. Three more patients died within the subsequent 9 months (2 patients had rapid massive hemorrhage and many bacilli reminiscent of Bacillus anthracis infection, and 1 patient had sparse bacilli, petechial hemorrhages, and border zone infarcts). Blood cultures yielded positive results in 3 of 5 cases. A possible route of infection was hematogenous dissemination via GI mucosal breaches (GI symptoms occurred in 3 of 5 cases, and postmortem GI ulceration was found in 3 of 4 cases). Bacilli were seen in 2 of 3 GI ulcerations. Epidemiologic work-up, including a site visit conducted by the Centers for Disease Control and Prevention, did not identify a clear common source but suggested the possibility of bananas as a food source. Bacillus cereus causes a rapidly progressive, hemorrhagic meningoencephalitis with high mortality among patients with neutropenia. Neuropathologists can play a key role in the detection of outbreaks. C1 [Vodopivec, Ivana] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Vodopivec, Ivana; Feske, Steven K.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Rinehart, Elizabeth M.; Griffin, Gabriel K.; Johncilla, Melanie E.; Pecora, Nicole; Milner, Danny A., Jr.; Folkerth, Rebecca D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Yokoe, Deborah S.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. RP Folkerth, RD (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, 75 Francis St, Boston, MA 02115 USA. EM rfolkerth@partners.org FU Department of Pathology, Brigham and Women's Hospital FX This study was supported by the Department of Pathology, Brigham and Women's Hospital. NR 29 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD OCT PY 2015 VL 74 IS 10 BP 1000 EP 1011 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DC2VQ UT WOS:000369076600006 PM 26352989 ER PT J AU Plenter, R Jain, S Ruller, CM Nydam, TL Jani, AH AF Plenter, Robert Jain, Swati Ruller, Chelsea M. Nydam, Trevor L. Jani, Alkesh H. TI Murine Kidney Transplant Technique SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 104; renal; transplant; mouse; immunology; rejection; surgery ID MICE; ANASTOMOSES; THROMBOSIS; VESSELS; INTACT AB The first mouse kidney transplant technique was published in 1973(1) by the Russell laboratory. Although it took some years for other labs to become proficient in and utilize this technique, it is now widely used by many laboratories around the world. A significant refinement to the original technique using the donor aorta to form the arterial anastomosis instead of the renal artery was developed and reported in 1993 by Kalina and Mottram (2) with a further advancement coming from the same laboratory in 1999 (3). While one can become proficient in this model, a search of the literature reveals that many labs still experience a high proportion of graft loss due to arterial thrombosis. We describe here a technique that was devised in our laboratory that vastly reduces the arterial thrombus reported by others (4,5). This is achieved by forming a heel-and-toe cuff of the donor infra-renal aorta that facilitates a larger anastomosis and straighter blood flow into the kidney. C1 [Plenter, Robert] Univ Colorado, Colorado Ctr Transplantat Care Res & Educ, Denver, CO 80202 USA. [Plenter, Robert] Univ Colorado, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. [Jain, Swati; Jani, Alkesh H.] Univ Colorado, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Denver, CO 80202 USA. [Jain, Swati; Jani, Alkesh H.] Univ Colorado, Denver, CO 80202 USA. [Ruller, Chelsea M.; Nydam, Trevor L.] Univ Colorado, Sch Med, Dept Surg, Denver, CO USA. [Jani, Alkesh H.] Denver Vet Affairs Med Ctr, Renal Sect, Denver, CO USA. RP Plenter, R (reprint author), Univ Colorado, Colorado Ctr Transplantat Care Res & Educ, Denver, CO 80202 USA. EM robert.plenter@ucdenver.edu FU [1R03DK096151] FX This work was supported in part by 1R03DK096151. NR 14 TC 1 Z9 1 U1 0 U2 0 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD OCT PY 2015 IS 104 AR e52848 DI 10.3791/52848 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB5SB UT WOS:000368572800011 PM 26555373 ER PT J AU Rochard, LJ Ling, ITC Kong, YW Liao, EC AF Rochard, Lucie J. Ling, Irving T. C. Kong, Yawei Liao, Eric C. TI Visualization of Chondrocyte Intercalation and Directional Proliferation via Zebrabow Clonal Cell Analysis in the Embryonic Meckel's Cartilage SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Developmental Biology; Issue 104; Craniofacial development; cranial neural crest; confocal microscopy; fate mapping; multi-spectral clonal analysis; sox10; Zebrabow; zebrafish; lower jaw; Meckel's cartilage ID CLEFT-LIP; ZEBRAFISH; MODEL AB Development of the vertebrate craniofacial structures requires precise coordination of cell migration, proliferation, adhesion and differentiation. Patterning of the Meckel's cartilage, a first pharyngeal arch derivative, involves the migration of cranial neural crest (CNC) cells and the progressive partitioning, proliferation and organization of differentiated chondrocytes. Several studies have described CNC migration during lower jaw morphogenesis, but the details of how the chondrocytes achieve organization in the growth and extension of Meckel's cartilage remains unclear. The sox10 restricted and chemically induced Cre recombinase-mediated recombination generates permutations of distinct fluorescent proteins (RFP, YFP and CFP), thereby creating a multi-spectral labeling of progenitor cells and their progeny, reflecting distinct clonal populations. Using confocal time-lapse photography, it is possible to observe the chondrocytes behavior during the development of the zebrafish Meckel's cartilage. Multispectral cell labeling enables scientists to demonstrate extension of the Meckel's chondrocytes. During extension phase of the Meckel's cartilage, which prefigures the mandible, chondrocytes intercalate to effect extension as they stack in an organized single-cell layered row. Failure of this organized intercalating process to mediate cell extension provides the cellular mechanistic explanation for hypoplastic mandible that we observe in mandibular malformations. C1 [Rochard, Lucie J.; Ling, Irving T. C.; Kong, Yawei; Liao, Eric C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Cambridge, MA 02138 USA. RP Liao, EC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Cambridge, MA 02138 USA. EM cliao@partners.org FU NIDCR [RO3DE024490]; Shriners Hospitals for Children FX We are grateful for generous funding support from NIDCR RO3DE024490 and Shriners Hospitals for Children (E.C.L.) and post-doctoral training fellowships from Shriners Hospitals for Children (L.R. and Y.K). NR 13 TC 0 Z9 0 U1 1 U2 2 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD OCT PY 2015 IS 104 AR e52935 DI 10.3791/52935 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB5SB UT WOS:000368572800015 PM 26555721 ER PT J AU Miyoshi, N Wittner, BS Shioda, K Hitora, T Ito, T Ramaswamy, S Isselbacher, KJ Sgroi, DC Shioda, T AF Miyoshi, N. Wittner, B. S. Shioda, K. Hitora, T. Ito, T. Ramaswamy, S. Isselbacher, K. J. Sgroi, D. C. Shioda, T. TI Nodes-and-connections RNAi knockdown screening: identification of a signaling molecule network involved in fulvestrant action and breast cancer prognosis SO ONCOGENESIS LA English DT Article ID INTERACTING PROTEIN-KINASE; ALPHA ER-ALPHA; ESTROGEN-RECEPTOR; ENDOCRINE THERAPY; HUMAN-CELLS; RESISTANCE; ACTIVATION; INHIBITORS; APOPTOSIS; FAMILY AB Although RNA interference (RNAi) knockdown screening of cancer cell cultures is an effective approach to predict drug targets or therapeutic/prognostic biomarkers, interactions among identified targets often remain obscure. Here, we introduce the nodes-and-connections RNAi knockdown screening that generates a map of target interactions through systematic iterations of in silico prediction of targets and their experimental validation. An initial RNAi knockdown screening of MCF-7 human breast cancer cells targeting 6560 proteins identified four signaling molecules required for their fulvestrant-induced apoptosis. Signaling molecules physically or functionally interacting with these four primary node targets were computationally predicted and experimentally validated, resulting in identification of four second-generation nodes. Three rounds of further iterations of the prediction-validation cycle generated third, fourth and fifth generation of nodes, completing a 19-node interaction map that contained three predicted nodes but without experimental validation because of technical limitations. The interaction map involved all three members of the death-associated protein kinases (DAPKs) as well as their upstream and downstream signaling molecules (calmodulins and myosin light chain kinases), suggesting that DAPKs play critical roles in the cytocidal action of fulvestrant. The in silico Kaplan-Meier analysis of previously reported human breast cancer cohorts demonstrated significant prognostic predictive power for five of the experimentally validated nodes and for three of the prediction-only nodes. Immunohistochemical studies on the expression of 10 nodal proteins in human breast cancer tissues not only supported their prognostic prediction power but also provided statistically significant evidence of their synchronized expression, implying functional interactions among these nodal proteins. Thus, the Nodes-and-Connections approach to RNAi knockdown screening yields biologically meaningful outcomes by taking advantage of the existing knowledge of the physical and functional interactions between the predicted target genes. The resulting interaction maps provide useful information on signaling pathways cooperatively involved in clinically important features of the malignant cells, such as drug resistance. C1 [Miyoshi, N.; Wittner, B. S.; Shioda, K.; Ramaswamy, S.; Isselbacher, K. J.; Shioda, T.] Massachusetts Gen Hosp, Ctr Canc Res, Bldg 147,7th Floor,13th St, Charlestown, MA 02129 USA. [Miyoshi, N.; Wittner, B. S.; Shioda, K.; Ramaswamy, S.; Isselbacher, K. J.; Sgroi, D. C.; Shioda, T.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Hitora, T.; Ito, T.] Rinku Gen Med Ctr, Dept Surg, Osaka, Japan. [Sgroi, D. C.] Massachusetts Gen Hosp, Mol Pathol, Charlestown, MA 02129 USA. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Bldg 147,7th Floor,13th St, Charlestown, MA 02129 USA. EM tshioda@mgh.harvard.edu FU Susan G Komen for Cure [FAS0703860, KG090515]; MGH-AstraZeneca Research Alliance FX This study was supported by Susan G Komen for Cure Grants FAS0703860 and KG090515, and the MGH-AstraZeneca Research Alliance Grant to TS. NR 57 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2157-9024 J9 ONCOGENESIS JI Oncogenesis PD OCT PY 2015 VL 4 AR e172 DI 10.1038/oncsis.2015.32 PG 9 WC Oncology SC Oncology GA DB7FE UT WOS:000368679300005 PM 26479444 ER PT J AU Payne, SN Maher, ME Tran, NH Van De Hey, DR Foley, TM Yueh, AE Leystra, AA Pasch, CA Jeffrey, JJ Clipson, L Matkowskyj, KA Deming, DA AF Payne, S. N. Maher, M. E. Tran, N. H. Van De Hey, D. R. Foley, T. M. Yueh, A. E. Leystra, A. A. Pasch, C. A. Jeffrey, J. J. Clipson, L. Matkowskyj, K. A. Deming, D. A. TI PIK3CA mutations can initiate pancreatic tumorigenesis and are targetable with PI3K inhibitors SO ONCOGENESIS LA English DT Article ID PAPILLARY MUCINOUS NEOPLASM/CARCINOMA; CELL LUNG-CANCER; DUCTAL ADENOCARCINOMA; CLINICAL-TRIALS; PATHWAY INHIBITORS; BREAST-CANCER; MICE; KRAS; GEMCITABINE; COOPERATE AB Aberrations in the phosphoinositide 3-kinase (PI3K) signaling pathway have a key role in the pathogenesis of numerous cancers by altering cell growth, metabolism, proliferation and apoptosis. Interest in targeting the PI3K signaling cascade continues, as new agents are being clinically evaluated. PIK3CA mutations result in a constitutively active PI3K and are present in a subset of pancreatic cancers. Here we examine mutant PIK3CA-mediated pancreatic tumorigenesis and the response of PIK3CA mutant pancreatic cancers to dual PI3K/mammalian target of rapamycin (mTOR) inhibition. Two murine models were generated expressing a constitutively active PI3K within the pancreas. An increase in acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasms (PanINs) was identified. In one model these lesions were detected as early as 10 days of age. Invasive pancreatic ductal adenocarcinoma developed in these mice as early as 20 days of age. These cancers were highly sensitive to treatment with dual PI3K/mTOR inhibition. In the second model, PanINs and invasive cancer develop with a greater latency owing to a lesser degree of PI3K pathway activation in this murine model. In addition to PI3K pathway activation, increased ERK1/2 signaling is common in human pancreatic cancers. Phosphorylation of ERK1/2 was also investigated in these models. Phosphorylation of ERK1/2 is demonstrated in the pre-neoplastic lesions and invasive cancers. This activation of ERK1/2 is diminished with dual PI3K/mTOR inhibition. In summary, PIK3CA mutations can initiate pancreatic tumorigenesis and these cancers are particularly sensitive to dual PI3K/mTOR inhibition. Future studies of PI3K pathway inhibitors for patients with PIK3CA mutant pancreatic cancers are warranted. C1 [Payne, S. N.; Pasch, C. A.; Jeffrey, J. J.; Matkowskyj, K. A.; Deming, D. A.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Maher, M. E.; Tran, N. H.; Van De Hey, D. R.; Foley, T. M.; Yueh, A. E.; Deming, D. A.] Univ Wisconsin, Dept Med, Div Hematol & Oncol, Madison, WI USA. [Leystra, A. A.; Clipson, L.] Univ Wisconsin, Dept Oncol, Madison, WI USA. [Matkowskyj, K. A.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA. [Matkowskyj, K. A.; Deming, D. A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Deming, DA (reprint author), Univ Wisconsin, Med, 600 Highland Ave,K6-544, Madison, WI 53792 USA. EM ddeming@medicine.wisc.edu FU National Institutes of Health [P30 CA014520]; UW Carbone Cancer Center; UW Department of Medicine; UW School of Medicine and Public Health; UW Graduate School through the Wisconsin Alumni Research Foundation FX This project was supported by the National Institutes of Health P30 CA014520 (Core Grant, University of Wisconsin Carbone Cancer Center); and start-up funds (DAD) from the UW Carbone Cancer Center, UW Department of Medicine, UW School of Medicine and Public Health, and the UW Graduate School through the Wisconsin Alumni Research Foundation. NR 45 TC 3 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2157-9024 J9 ONCOGENESIS JI Oncogenesis PD OCT PY 2015 VL 4 AR e169 DI 10.1038/oncsis.2015.28 PG 10 WC Oncology SC Oncology GA DB7FE UT WOS:000368679300002 PM 26436951 ER PT J AU Kotton, CN AF Kotton, Camille Nelson TI Taming the Beast: Tailored Therapy for Hepatitis E in Organ Transplant Recipients SO TRANSPLANTATION LA English DT Editorial Material ID E VIRUS-INFECTION C1 [Kotton, Camille Nelson] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Harvard Univ, Sch Med, Div Infect Dis, Massachusetts Gen Hosp, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 9 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD OCT PY 2015 VL 99 IS 10 BP 2020 EP 2021 DI 10.1097/TP.0000000000000849 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DC2ZC UT WOS:000369086800008 PM 26214818 ER PT J AU Thanos, A Gilbert, AL Gragoudas, ES AF Thanos, Aristomenis Gilbert, Aubrey L. Gragoudas, Evangelos S. TI Severe Vision Loss With Optic Disc Neovascularization After Hemiretinal Vascular Obstruction Associated With Optic Disc Melanocytoma SO JAMA OPHTHALMOLOGY LA English DT Editorial Material C1 [Thanos, Aristomenis; Gilbert, Aubrey L.; Gragoudas, Evangelos S.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Thanos, A (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM athanos@meei.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD OCT PY 2015 VL 133 IS 10 AR e151502 PG 1 WC Ophthalmology SC Ophthalmology GA CT7AL UT WOS:000362965300002 PM 26448432 ER PT J AU Lozano, BE Gros, DF Killeen, T Jaconis, M Beylotte, FM Boyd, S Back, SE AF Lozano, Brian E. Gros, Daniel F. Killeen, Therese Jaconis, Maryanne Beylotte, Francis M., III Boyd, Stephen Back, Sudie E. TI To Reduce or Abstain? Substance Use Goals in the Treatment of Veterans With Substance Use Disorders and Comorbid PTSD SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ABSTINENCE; THERAPY; PREDICTORS; DEPENDENCE; DRINKING AB Background: Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) frequently co-occur. Previous research demonstrates the utility of goals in attaining improved SUD outcomes, however, no previous studies have examined goal choices in the context of integrated treatment for comorbid PTSD and SUD. Objectives: The present study investigated correlates of treatment entry goals to either reduce or abstain from substance use. Methods: Participants (N = 60) were treatment-seeking veterans with current PTSD and SUD. Participants completed self-report and clinician-rated measures of substance use, PTSD, and affective symptoms as part of a larger randomized controlled trial. Results: Half (30/60) of participants endorsed a treatment entry goal to reduce substance use (reducers). Compared to participants who endorsed a treatment entry goal of abstinence (abstainers), reducers were significantly younger, more likely to be employed, more likely to have served in recent military conflicts (Operations Enduring/Iraqi Freedom), and endorsed significantly fewer symptoms of alcohol dependence. Conclusions and Scientific Significance: The findings demonstrate clinically relevant differences based on treatment entry goals, suggesting that individuals are often able to choose conceivably appropriate treatment goals based, most notably, on the severity of their SUD. Collaboratively engaging patients in establishing treatment goals that are consistent with their beliefs and desires in conjunction with empirical findings is particularly relevant in the context of treatment for SUD and PTSD where many patients are ambivalent about treatment and attrition is common. C1 [Lozano, Brian E.; Gros, Daniel F.; Back, Sudie E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Lozano, Brian E.; Gros, Daniel F.; Killeen, Therese; Jaconis, Maryanne; Beylotte, Francis M., III; Boyd, Stephen; Back, Sudie E.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Lozano, BE (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM Brian.Lozano@va.gov FU NIDA [DA021228]; NIAAA [T32 AA007474]; Veterans Affairs Clinical Sciences Research and Development [CX000845] FX The authors would like to acknowledge support from NIDA grant number DA021228 (Back, S. E.), NIAAA T32 AA007474 (Woodward, J.), Veterans Affairs Clinical Sciences Research and Development CX000845 (Gros, D. F.). NR 25 TC 2 Z9 2 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD OCT PY 2015 VL 24 IS 7 BP 578 EP 581 DI 10.1111/ajad.12263 PG 4 WC Substance Abuse SC Substance Abuse GA DB4SD UT WOS:000368502500001 PM 26300219 ER PT J AU Jacobs, P Ang, A Hillhouse, MP Saxon, AJ Nielsen, S Wakim, PG Mai, BE Mooney, LJ Potter, JS Blaine, JD AF Jacobs, Petra Ang, Alfonso Hillhouse, Maureen P. Saxon, Andrew J. Nielsen, Suzanne Wakim, Paul G. Mai, Barbara E. Mooney, Larissa J. Potter, Jennifer S. Blaine, Jack D. TI Treatment Outcomes in Opioid Dependent Patients With Different Buprenorphine/Naloxone Induction Dosing Patterns and Trajectories SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID MAINTENANCE TREATMENT; METHADONE; RETENTION; TRIAL; EXPERIENCE; PREDICTORS; HEALTH AB Background and Objectives: Induction is a crucial period of opioid addiction treatment. This study aimed to identify buprenorphine/naloxone (BUP) induction patterns and examine their association with outcomes (opioid use, retention, and related adverse events [AEs]). Methods: The secondary analysis of a study of opioid-dependent adults seeking treatment in eight treatment settings included 740 participants inducted on BUP with flexible dosing. Results: Latent class analysis models detected six distinctive induction trajectories: bup1-started and remained on low; bup2started low, shifted slowly to moderate; bup3-started low, shifted quickly to moderate; bup4-started high, shifted to low; bup5-started and remained on moderate; bup6-started moderate, shifted to high dose (Fig. 1). Baseline characteristics, including Clinical Opioid Withdrawal Scale (COWS), were important predictors of retention. When controlled for the baseline characteristics, bup6 participants were three times less likely to drop out the first 7 days than bup1 participants (adjusted hazard ratio (aHR) = .28, p = .03). Opioid use and AEs were similar across trajectories. Participants on >= 16 mg BUP compared to those on < 16 mg at Day 28 were less likely to drop out (aHR = .013, p = .001) and less likely to have AEs during the first 28 days (aOR = .57, p = .03). Discussion and Conclusions: BUP induction dosing was guided by an objective measure of opioid withdrawal. Participants with higher baseline COWS whose BUP doses were raised more quickly were less likely to drop out in the first 7 days than those whose doses were raised slower. Scientific Significance: This study supports the use of an objective measure of opioid withdrawal (COWS) during BUP induction to improve retention early in treatment. C1 [Jacobs, Petra; Blaine, Jack D.] EMMES Corp, Rockville, MD USA. [Ang, Alfonso; Hillhouse, Maureen P.; Mooney, Larissa J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Saxon, Andrew J.] VA Puget Sound Hlth Care, Seattle, WA USA. [Nielsen, Suzanne] Univ New S Wales, Natl Drug & Alcohol Res Ctr, Sydney, NSW, Australia. [Wakim, Paul G.] NIDA, Ctr Clin Trials Network, Rockville, MD USA. [Mai, Barbara E.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Potter, Jennifer S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Jacobs, P (reprint author), EMMES Corp, Rockville, MD USA. EM petraejacobs@gmail.com OI Nielsen, Suzanne/0000-0001-5341-1055 FU National Institute on Drug Abuse; Clinical Trials Network: Pacific Northwest Node, NIH/NIDA [5 U10 DA013714-08]; NHMRC [1013803] FX The original START study was funded by the National Institute on Drug Abuse, where the buprenorphine/naloxone for START was provided by Reckitt Benckiser Pharmaceuticals. The authors of this secondary analysis collaborated on the implementation of START and received the dataset. Dr. Saxon has grant support from the Clinical Trials Network: Pacific Northwest Node. 5 U10 DA013714-08, NIH/NIDA, served on the Pharmaceutical, Scientific Advisory Board, Alkermes, Inc. and has been a presenter for Reckitt-Benckiser, Inc. He has no publishing constraints. Dr. Nielsen is supported by a NHMRC Research Fellowship (#1013803), has been an investigator on united educational grants from Reckitt-Benckiser, completely unrelated to this work, no publishing constraints. Dr. Blaine has been a treatment advocate for Reckitt Benckiser Pharmaceuticals, Inc., with no publishing constraints. The authors alone are responsible for the content and writing of this paper. NR 23 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD OCT PY 2015 VL 24 IS 7 BP 667 EP 675 DI 10.1111/ajad.12288 PG 9 WC Substance Abuse SC Substance Abuse GA DB4SD UT WOS:000368502500014 PM 26400835 ER PT J AU DuBrock, HM Goldberg, DS Sussman, NL Bartolome, S Kadry, Z Salgia, R De Wolf, AM Mulligan, DC Kawut, SM Krowka, MJ Channick, R AF DuBrock, Hilary M. Goldberg, David S. Sussman, Norman L. Bartolome, Sonja Kadry, Zakiyah Salgia, Reena De Wolf, Andre M. Mulligan, David C. Kawut, Steven M. Krowka, Michael J. Channick, Richard TI Prediction of waitlist mortality in patients with portopulmonary hypertension (POPH): An analysis of the UNOS database SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [DuBrock, Hilary M.] Beth Israel Deaconess Med Ctr, Med, Boston, MA 02215 USA. [DuBrock, Hilary M.; Channick, Richard] Massachusetts Gen Hosp, Med, Boston, MA 02114 USA. [Krowka, Michael J.] Mayo Clin, Rochester, MN USA. [Goldberg, David S.; Kawut, Steven M.] Univ Penn, Philadelphia, PA 19104 USA. [Sussman, Norman L.] Baylor Coll Med, Houston, TX 77030 USA. [Bartolome, Sonja] UT Southwestern, Dallas, TX USA. [Kadry, Zakiyah] Penn State Hershey Med Ctr, Hershey, PA USA. [Salgia, Reena] Henry Ford Hosp, Detroit, MI 48202 USA. [De Wolf, Andre M.] Northwester Univ, Chicago, IL USA. [Mulligan, David C.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 9 BP 212A EP 212A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375400010 ER PT J AU Kaplan, DE Taddei, TH Mehta, R Dai, F Hunt, KK Aytaman, A Fox, RK Baytarian, M Pedrosa, MC Pocha, C Valderama, A AF Kaplan, David E. Taddei, Tamar H. Mehta, Rajni Dai, Feng Hunt, Kristel K. Aytaman, Ayse Fox, Rena K. Baytarian, Michelle Pedrosa, Marcos C. Pocha, Christine Valderama, Adriana TI Modernizing the Child-Turcotte-Pugh score in the era of big data: an analysis of 30,897 cirrhotic patients SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kaplan, David E.] Univ Penn, Philadelphia, PA 19104 USA. [Kaplan, David E.] Corporal Michael J Crescenz Vet Affairs Med Ctr, Philadelphia, PA USA. [Taddei, Tamar H.; Mehta, Rajni] West Haven VA Med Ctr, West Haven, CT USA. [Aytaman, Ayse] VA New York Harbor Med Ctr, Brooklyn, NY USA. [Hunt, Kristel K.] JJ Peters Vet Affairs Med Ctr, Med, Bronx, NY USA. [Fox, Rena K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Taddei, Tamar H.; Mehta, Rajni; Dai, Feng] Yale Univ, Sch Med, New Haven, CT USA. [Valderama, Adriana] Bayer Healthcare Pharmaceut, Whippany, NJ USA. [Baytarian, Michelle; Pedrosa, Marcos C.] VA Boston Healthcare Syst, Boston, MA USA. [Pocha, Christine] Univ Bern, Hepatol, Bern, Switzerland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 16 BP 215A EP 215A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375400017 ER PT J AU Ioannou, GN Berry, K AF Ioannou, George N. Berry, Kristin TI Comparison of Liver Transplant-related Survival Benefit in Patients With vs Without Hepatocellular Carcinoma in the United States. SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Ioannou, George N.; Berry, Kristin] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 49 BP 232A EP 233A PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375400050 ER PT J AU El-Serag, HB Richardson, P Kanwal, F AF El-Serag, Hashem B. Richardson, Peter Kanwal, Fasiha TI Incidence and Predictors of hepatocellular Carcinoma following Sustained Virological Response: A national Cohort Study SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Richardson, Peter; Kanwal, Fasiha] Emory Univ, Med Gastroenterol & Hepatol, Houston, TX USA. [El-Serag, Hashem B.] Houston VA Med Ctr, Houston, TX USA. [El-Serag, Hashem B.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 90 BP 253A EP 254A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375400091 ER PT J AU Muir, AJ Charlton, MR Pang, PS Stamm, LM Brainard, DM McHutchison, JG Afdhal, NH Watkins, PB AF Muir, Andrew J. Charlton, Michael R. Pang, Phillip S. Stamm, Luisa M. Brainard, Diana M. McHutchison, John G. Afdhal, Nezam H. Watkins, Paul B. TI Detecting Drug-Induced Liver Injury in Patients with Decompensated Chronic Hepatitis C: A Review of the SOLAR-1 and SOLAR-2 Studies SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Pang, Phillip S.; Stamm, Luisa M.; Brainard, Diana M.; McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Muir, Andrew J.] Duke Univ, Med Ctr, Durham, NC USA. [Afdhal, Nezam H.] BIDMC, Div Gastroenterol, Boston, MA USA. [Watkins, Paul B.] Hamner UNC Inst Drug Safety Sci, Chapel Hill, NC USA. [Charlton, Michael R.] Intermt Med Ctr, Murray, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 96 BP 257A EP 258A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375400097 ER PT J AU Beste, LA Leipertz, S Green, P Dominitz, JA Ross, D Ioannou, GN AF Beste, Lauren A. Leipertz, Steven Green, Pamela Dominitz, Jason A. Ross, David Ioannou, George N. TI Trends in the burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US Veterans from 2001-2013 SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Dominitz, Jason A.; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Beste, Lauren A.; Leipertz, Steven; Green, Pamela; Dominitz, Jason A.; Ioannou, George N.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Ross, David] Dept Vet Affairs, Off Publ Hlth, Washington, DC USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 128 BP 274A EP 274A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401013 ER PT J AU Klebanoff, M Corey, KE Kaplan, LM Chung, RT Hur, C AF Klebanoff, Matthew Corey, Kathleen E. Kaplan, Lee M. Chung, Raymond T. Hur, Chin TI Bariatric surgery for the treatment of nonalcoholic steatohepatitis: Results of a Markov Model SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Klebanoff, Matthew] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Klebanoff, Matthew; Corey, Kathleen E.; Kaplan, Lee M.; Chung, Raymond T.; Hur, Chin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Corey, Kathleen E.; Kaplan, Lee M.; Chung, Raymond T.; Hur, Chin] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 154 BP 287A EP 287A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401039 ER PT J AU Sulkowski, MS Brau, N Lawitz, E Shiffman, ML Towner, WJ Ruane, PJ Doehle, B Wang, J McNally, J Osinusi, A Brainard, DM McHutchison, JG Reau, N Patel, K AF Sulkowski, Mark S. Brau, Norbert Lawitz, Eric Shiffman, Mitchell L. Towner, William J. Ruane, Peter J. Doehle, Brian Wang, Jing McNally, John Osinusi, Anu Brainard, Diana M. McHutchison, John G. Reau, Nancy Patel, Keyur TI A Randomized Controlled Trial of Sofosbuvir/GS-5816 Fixed Dose Combination for 12 Weeks Compared to Sofosbuvir with Ribavirin for 12 Weeks in Genotype 2 HCV Infected Patients: The Phase 3 ASTRAL-2 Study SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Sulkowski, Mark S.] Johns Hopkins Univ, Baltimore, MD USA. [Brau, Norbert] James J Peters VA Med Ctr, Bronx, NY USA. [Brau, Norbert] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Lawitz, Eric] Univ Texas Hlth Sci Ctr San Antonio, Texas Liver Inst, San Antonio, TX 78229 USA. [Shiffman, Mitchell L.] Liver Inst Virginia, Richmond, VA USA. [Towner, William J.] Kaiser Permanente, Los Angeles, CA USA. [Ruane, Peter J.] Ruane Med, Los Angeles, CA USA. [Doehle, Brian; Wang, Jing; McNally, John; Osinusi, Anu; Brainard, Diana M.; McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Reau, Nancy] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Patel, Keyur] Duke Univ, Sch Med, Durham, NC USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 205 BP 313A EP 313A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401090 ER PT J AU Liberal, R Grant, CR Holder, BS Ma, Y Heneghan, MA Mieli-Vergani, G Vergani, D Longhi, MS AF Liberal, Rodrigo Grant, Charlotte R. Holder, Beth S. Ma, Yun Heneghan, Michael A. Mieli-Vergani, Giorgina Vergani, Diego Longhi, Maria Serena TI In autoimmune liver disease defective regulatory T cell responsiveness to IL-2 results in low IL-10 production and impaired suppression SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Liberal, Rodrigo; Grant, Charlotte R.; Holder, Beth S.; Ma, Yun; Heneghan, Michael A.; Mieli-Vergani, Giorgina; Vergani, Diego; Longhi, Maria Serena] Kings Coll London, Inst Liver Studies, London WC2R 2LS, England. [Mieli-Vergani, Giorgina] Kings Coll London, Paediat Liver GI & Nutr Ctr, London WC2R 2LS, England. [Longhi, Maria Serena] Harvard Univ, BIDMC, Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 300 BP 364A EP 364A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401185 ER PT J AU Talal, AH Furlage, R Woolwine-Cunningham, YJ Li, J Difrancesco, R Morse, GD Lauer, G Qu, J Wallace, PK AF Talal, Andrew H. Furlage, Rosemary Woolwine-Cunningham, Yvonne J. Li, Jun Difrancesco, Robin Morse, Gene D. Lauer, Georg Qu, Jun Wallace, Paul K. TI Hepatocyte Isolation from Liver Fine Needle Aspiration and Core Needle Biopsy SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Talal, Andrew H.; Woolwine-Cunningham, Yvonne J.] SUNY Buffalo, Ctr Clin Care & Res Liver Dis, Buffalo, NY 14260 USA. [Talal, Andrew H.] SUNY Buffalo, Dept Med, Div Gastroenterol Hepatol & Nutr, Buffalo, NY 14260 USA. [Furlage, Rosemary; Wallace, Paul K.] Roswell Pk Canc Inst, Dept Flow & Image Cytometry, Buffalo, NY 14263 USA. [Li, Jun; Difrancesco, Robin; Morse, Gene D.; Qu, Jun] SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Buffalo, NY 14260 USA. [Difrancesco, Robin; Morse, Gene D.] SUNY Buffalo, NYS Ctr Excellence Bioinformat & Life Sci, Buffalo, NY 14260 USA. [Lauer, Georg] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 332 BP 379A EP 379A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401217 ER PT J AU Minguez, B Aytaman, A Ventura-Cots, M Badshah, MB Citti, CC Platt, HL Chen, TY Kikuchi, L Marcus, S Yin, M Aberg, J Dieterich, D Schwartz, ME Brau, N AF Minguez, Beatriz Aytaman, Ayse Ventura-Cots, Meritxell Badshah, Maaz B. Citti, Caitlin C. Platt, Heather L. Chen, Ting-Yi Kikuchi, Luciana Marcus, Sonja Yin, Michael Aberg, Judith Dieterich, Douglas Schwartz, Myron E. Braeu, Norbert TI Trends of Hepatocellular Carcinoma (HCC) in HIV-Infected Patients over Time, 1995-2013 SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Minguez, Beatriz; Ventura-Cots, Meritxell] Hosp Univ Vall dHebron, Liver Unit, Barcelona, Spain. [Aytaman, Ayse] VA New York Harbor HCS, Brooklyn, NY USA. [Aytaman, Ayse] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Badshah, Maaz B.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Citti, Caitlin C.; Aberg, Judith; Dieterich, Douglas; Braeu, Norbert] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Platt, Heather L.; Yin, Michael] Columbia Univ, Med Ctr, Div Infect Dis, New York, NY USA. [Chen, Ting-Yi] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kikuchi, Luciana] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Marcus, Sonja; Braeu, Norbert] James J Peters VA Med Ctr, Bronx, NY USA. [Schwartz, Myron E.] Icahn Sch Med Mt Sinai, Dept Surg, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 380 BP 402A EP 403A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401264 ER PT J AU Kikuchi, L Citti, CC Chen, TY Platt, HL Kaplan, DE Ventura-Cots, M Jain, MK Vispo, E Daruich, J Nunez, M Barreiro, P Minguez, B Aytaman, A Rimland, D Brau, N AF Kikuchi, Luciana Citti, Caitlin C. Chen, Ting-Yi Platt, Heather L. Kaplan, David E. Ventura-Cots, Meritxell Jain, Mamta K. Vispo, Eugenia Daruich, Jorge Nunez, Marina Barreiro, Pablo Minguez, Beatriz Aytaman, Ayse Rimland, David Braeu, Norbert TI Sorafenib Therapy in HIV-infected Patients with Hepatocellular Carcinoma (HCC) SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kikuchi, Luciana] Univ Sao Paulo, Gastroenterol, Sao Paulo, Brazil. [Citti, Caitlin C.; Braeu, Norbert] Icahn Sch Med Mt Sinai, Infectious Dis & Liver Dis, New York, NY 10029 USA. [Citti, Caitlin C.; Platt, Heather L.; Braeu, Norbert] James J Peters VA Med Ctr, Bronx, NY USA. [Chen, Ting-Yi; Jain, Mamta K.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kaplan, David E.] Univ Penn, Philadelphia, PA 19104 USA. [Ventura-Cots, Meritxell] Hosp Univ Vall dHebron, Barcelona, Spain. [Vispo, Eugenia; Barreiro, Pablo] Hosp Carlos III, Madrid, Spain. [Daruich, Jorge] Univ Buenos Aires, Buenos Aires, DF, Argentina. [Nunez, Marina] Wake Forest Univ, Winston Salem, NC 27109 USA. [Aytaman, Ayse] VA New York Harbor HCS, Brooklyn, NY USA. [Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 438 BP 430A EP 430A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401321 ER PT J AU Badshah, MB Ventura-Cots, M Citti, CC Kikuchi, L Marcus, S Minguez, B Chen, TY Hernandez, MD Aberg, J Schwartz, ME Dieterich, D Brau, N AF Badshah, Maaz B. Ventura-Cots, Meritxell Citti, Caitlin C. Kikuchi, Luciana Marcus, Sonja Minguez, Beatriz Chen, Ting-Yi Hernandez, Maria D. Aberg, Judith Schwartz, Myron E. Dieterich, Douglas Braeu, Norbert TI Improved Survival of Hepatocellular Carcinoma (HCC) in HIV/Hepatitis B Virus (HBV)-Coinfected Patients Who Are Diagnosed Through HCC Screening SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Badshah, Maaz B.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Ventura-Cots, Meritxell] Hosp Univ Vall Hebron, Barcelona, Spain. [Citti, Caitlin C.; Aberg, Judith; Dieterich, Douglas; Braeu, Norbert] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Kikuchi, Luciana] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Marcus, Sonja; Braeu, Norbert] James J Peters VA Med Ctr, Bronx, NY USA. [Minguez, Beatriz] Hosp Univ Vall dHebron, Barcelona, Spain. [Chen, Ting-Yi] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Hernandez, Maria D.] Univ Miami, Sch Med, Miami, FL USA. [Schwartz, Myron E.] Icahn Sch Med Mt Sinai, Dept Surg, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 457 BP 439A EP 440A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401340 ER PT J AU Kriss, M Edwards, M Golden-Mason, L Larson, C Diener, K Rosen, HR AF Kriss, Michael Edwards, Michael Golden-Mason, Lucy Larson, Colin Diener, Katrina Rosen, Hugo R. TI High-throughput sequencing to define the miRNA cargo of LSEC-derived, anti-viral exosomes SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kriss, Michael; Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado, Div Gastroenterol & Hepatol, Aurora, CO USA. [Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. [Edwards, Michael] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Larson, Colin; Diener, Katrina] Univ Colorado, Genom & Microarray Core, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 503 BP 461A EP 462A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401386 ER PT J AU Egert, EM Johnson, RD Watts, MM Booty, J Damjanov, N Mohr, R Griffiths, J Lee, M Shaikh, HA Hawley, RC Ghosh, MS Mungiole, NS Kaplan, DE AF Egert, E. M. Johnson, Rena D. Watts, Micah M. Booty, Jordan Damjanov, Nevena Mohr, Rosemary Griffiths, Jenifer Lee, Major Shaikh, Haroon A. Hawley, Richard C. Ghosh, Martha S. Mungiole, Nicole S. Kaplan, David E. TI A Regional Multidisciplinary Liver Tumor Board improves Access to Hepatocellular Carcinoma Treatment for Patients Geographically Distant from Tertiary Medical Center SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Egert, E. M.] Coatesville VA Med Ctr, Cochranville, PA USA. [Johnson, Rena D.] Wilmington VA Med Ctr, Wilmington, DE USA. [Watts, Micah M.; Booty, Jordan; Damjanov, Nevena; Mohr, Rosemary; Lee, Major; Mungiole, Nicole S.; Kaplan, David E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Griffiths, Jenifer; Shaikh, Haroon A.; Hawley, Richard C.] Lebanon VA Med Ctr, Lebanon, PA USA. [Ghosh, Martha S.] Wilkes Barre VA Med Ctr, Wilkes Barre, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 521 BP 469A EP 469A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401404 ER PT J AU Hunt, CM Beste, LA Ioannou, GN Lowy, E Provenzale, DT Kelley, MJ Suzuki, A Moylan, CA Oloruntoba, OO Tillmann, HL Lim, JK Ross, D AF Hunt, Christine M. Beste, Lauren A. Ioannou, George N. Lowy, Elliott Provenzale, Dawn T. Kelley, Michael J. Suzuki, Ayako Moylan, Cynthia A. Oloruntoba, Omobonike O. Tillmann, Hans L. Lim, Joseph K. Ross, David TI Hepatitis B Testing Prior to Administration of Rituximab, Ofatumumab and Obinutuzumab in the National Veterans Affairs Health Healthcare System, 2002-2014 SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Hunt, Christine M.; Provenzale, Dawn T.; Kelley, Michael J.; Moylan, Cynthia A.; Oloruntoba, Omobonike O.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Hunt, Christine M.; Provenzale, Dawn T.; Kelley, Michael J.; Moylan, Cynthia A.; Oloruntoba, Omobonike O.] Durham VA Med Ctr, Dept Med, Durham, NC USA. [Ross, David] USDA, Off Publ Hlth, Washington, DC 20250 USA. [Beste, Lauren A.; Ioannou, George N.; Lowy, Elliott] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Ioannou, George N.; Lowy, Elliott] Univ Washington, Seattle, WA 98195 USA. [Suzuki, Ayako] Univ Arkansas Med Sci, Dept Med, Div Hepatol, Little Rock, AR 72205 USA. [Lim, Joseph K.] Yale Univ, Sch Med, Dept Med, Div Hepatol, New Haven, CT 06510 USA. [Tillmann, Hans L.] Eastern Carolina Univ, Dept Med, Greenville, NC USA. [Suzuki, Ayako] Cent Arkansas Vet Heathcare Syst, Dept Med, Div Hepatol, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 540 BP 478A EP 479A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401423 ER PT J AU Liberal, R Grant, CR Ma, Y Heneghan, MA Mieli-Vergani, G Vergani, D Robson, SC Longhi, MS AF Liberal, Rodrigo Grant, Charlotte R. Ma, Yun Heneghan, Michael A. Mieli-Vergani, Giorgina Vergani, Diego Robson, Simon C. Longhi, Maria Serena TI CD39 expression regulates Th17 cell effector function and is perturbed in autoimmune hepatitis/sclerosing cholangitis SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Liberal, Rodrigo; Grant, Charlotte R.; Ma, Yun; Heneghan, Michael A.; Mieli-Vergani, Giorgina; Vergani, Diego; Longhi, Maria Serena] Kings Coll London, Inst Liver Studies, London WC2R 2LS, England. [Mieli-Vergani, Giorgina] Kings Coll London, Paediat Liver GI & Nutr Ctr, London WC2R 2LS, England. [Robson, Simon C.; Longhi, Maria Serena] Harvard Univ, BIDMC, Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 608 BP 510A EP 511A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401491 ER PT J AU Mantry, PS Smith, HL Chung, RT Chapman, WC Curry, MP Schiano, TD Wang, Y Molrine, DC AF Mantry, Parvez S. Smith, Heidi L. Chung, Raymond T. Chapman, William C. Curry, Michael P. Schiano, Thomas D. Wang, Yang Molrine, Deborah C. TI Prevention of allograft HCV reinfection with peri-transplant MBL-HCV1 monoclonal antibody in combination with oral direct-acting antiviral SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Mantry, Parvez S.] Methodist Dallas Med Ctr, Liver Inst, Dallas, TX USA. [Smith, Heidi L.; Wang, Yang; Molrine, Deborah C.] Univ Massachusetts, Sch Med, MassBiol, Boston, MA 02125 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Chapman, William C.] Washington Univ, Dept Surg, St Louis, MA USA. [Curry, Michael P.] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. [Schiano, Thomas D.] Mt Sinai Med Ctr, Recanati Miller Transplantat Inst, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 704 BP 557A EP 558A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402029 ER PT J AU Yarnykh, VL Tartaglione, E Ioannou, GN AF Yarnykh, Vasily L. Tartaglione, Erica Ioannou, George N. TI Fast macromolecular proton fraction (MPF) mapping of the human liver in vivo for quantitative assessment of hepatic fibrosis SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Yarnykh, Vasily L.] Univ Washington, Radiol, Seattle, WA 98195 USA. [Yarnykh, Vasily L.] Tomsk State Univ, Biol & Biophys Res Inst, Tomsk, Russia. [Tartaglione, Erica; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA USA. [Ioannou, George N.] Univ Washington, Div Gastroenterol, Med, Seattle, WA 98195 USA. RI Yarnykh, Vasily/G-8757-2016; Yarnykh, Vasiliy/N-7635-2014 OI Yarnykh, Vasily/0000-0002-1583-8979; NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 803 BP 609A EP 609A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402127 ER PT J AU Goldberg, DS Karp, SJ Heimbach, J Markmann, JF Gilroy, R Hernandez-Alejandro, R Abt, PL AF Goldberg, David S. Karp, Seth J. Heimbach, Julie Markmann, James F. Gilroy, Richard Hernandez-Alejandro, Roberto Abt, Peter L. TI Preliminary Data Analysis from the Improving DCD Outcomes in Liver Transplantation (IDOL) Consortium SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Goldberg, David S.] Hosp Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Abt, Peter L.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Karp, Seth J.] Vanderbilt Univ, Dept Surg, Nashville, TN 37240 USA. [Gilroy, Richard] Univ Kansas, Dept Med, Kansas City, KS USA. [Heimbach, Julie] Mayo Clin, Dept Surg, Rochest, MN USA. [Markmann, James F.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hernandez-Alejandro, Roberto] London Hlth Sci Ctr, Dept Surg, London, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 837 BP 625A EP 625A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402161 ER PT J AU Ioannou, GN Subramanian, S Chait, A Yeh, MM Haigh, WG Savard, C AF Ioannou, George N. Subramanian, Savitha Chait, Alan Yeh, Matthew M. Haigh, W. G. Savard, Christopher TI Cholesterol crystallization within hepatocyte lipid droplets and its role in NASH SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Ioannou, George N.; Subramanian, Savitha; Chait, Alan; Yeh, Matthew M.; Savard, Christopher] Univ Washington, Seattle, WA 98195 USA. [Ioannou, George N.; Haigh, W. G.; Savard, Christopher] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 923 BP 664A EP 664A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402247 ER PT J AU Harriman, G DePeralta, DK Moaven, O Wei, L Greenwood, JR Bhat, SP Tanabe, KK Fuchs, BC Westlin, W Harwood, HJ Kapeller, R AF Harriman, Geraldine DePeralta, Danielle K. Moaven, Omeed Wei, Lan Greenwood, Jeremy R. Bhat, Sathesh P. Tanabe, Kenneth K. Fuchs, Bryan C. Westlin, William Harwood, H. James Kapeller, Rosana TI Liver-Directed Allosteric Inhibitors of Acetyl-CoA Carboxylase Reduce Hepatic Steatosis and Improve Dyslipidemia in Diet-Induced Obese Rat Models and Reduce Inflammation and Fibrosis in a Cirrhotic Rat Model SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Harriman, Geraldine; Westlin, William; Harwood, H. James; Kapeller, Rosana] Nimbus Therapeut, Cambridge, MA USA. [DePeralta, Danielle K.; Moaven, Omeed; Wei, Lan; Tanabe, Kenneth K.; Fuchs, Bryan C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenwood, Jeremy R.; Bhat, Sathesh P.] Schrodinger, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 957 BP 679A EP 680A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402281 ER PT J AU Liu, X Hong, J Cai, DC Lee, SH Fusco, D Schaefer, EA Brisac, C Lidofsky, A Lin, WY Chung, RT AF Liu, Xiao Hong, Jian Cai, Dachuan Lee, Sae Hwan Fusco, Dahlene Schaefer, Esperance A. Brisac, Cynthia Lidofsky, Anna Lin, Wenyu Chung, Raymond T. TI Long noncoding RNAs regulate HCV replication and ISGs in a Jak-STAT independent manner SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Liu, Xiao; Hong, Jian; Cai, Dachuan; Lee, Sae Hwan; Fusco, Dahlene; Schaefer, Esperance A.; Brisac, Cynthia; Lidofsky, Anna; Lin, Wenyu; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 991 BP 695A EP 695A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402315 ER PT J AU Walsh, C Workowski, K Terrault, N Sax, P Cohen, A Bowlus, CL Kim, AY Hyland, RH Wang, J Stamm, LM Brainard, DM McHutchison, JG Von Drygalski, A Rhame, FS Fried, MW Kouides, P Balba, G Reddy, KR AF Walsh, Christopher Workowski, Kimberly Terrault, Norah Sax, Paul Cohen, Alice Bowlus, Christopher L. Kim, Arthur Y. Hyland, Robert H. Wang, Jing Stamm, Luisa M. Brainard, Diana M. McHutchison, John G. Von Drygalski, Annette Rhame, Frank S. Fried, Michael W. Kouides, Peter Balba, Gayle Reddy, K. Rajender TI Approved All-oral Sofosbuvir Regimens are Safe and Highly Effective in Patients with Hereditary Bleeding Disorders SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Walsh, Christopher] Mt Sinai Hosp, New York, NY 10029 USA. [Workowski, Kimberly] Emory Univ, Atlanta, GA 30322 USA. [Terrault, Norah] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sax, Paul] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cohen, Alice] Newark Beth Israel Ctr Barnabas Hlth, Newark, NJ USA. [Bowlus, Christopher L.] Univ Calif Davis, Sacramento, CA USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hyland, Robert H.; Wang, Jing; Stamm, Luisa M.; Brainard, Diana M.; McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Von Drygalski, Annette] Univ Calif San Diego, San Diego, CA 92103 USA. [Rhame, Frank S.] Abbott NW Infect Dis Clin, Minneapolis, MN USA. [Fried, Michael W.] Univ N Carolina, Chapel Hill, NC USA. [Kouides, Peter] Mary M Gooley Hemophilia Ctr, Rochester, NY USA. [Balba, Gayle] Georgetown Univ Hosp, Washington, DC 20007 USA. [Reddy, K. Rajender] Univ Penn, Philadelphia, PA 19104 USA. RI Bowlus, Christopher/N-9276-2016 OI Bowlus, Christopher/0000-0002-3906-6811 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1034 BP 714A EP 714A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402357 ER PT J AU Basu, P Shah, NJ John, N Aloysius, M Brown, R AF Basu, Patrick Shah, Niraj J. John, Nimy Aloysius, M. Brown, Robert TI Sofosbuvir and Ledipasvir in attainment of SVR12 in sickle cell disease (SCD) sub-population with chronic hepatitis C (CHC). a single center prospective open label clinical pilot study - SLASH C Trial SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Basu, Patrick] Columbia Univ, Sch Phys & Surg, Forest Hills, NY USA. [Basu, Patrick; John, Nimy; Aloysius, M.] Kings Cty Hosp, Med Ctr, New York, NY USA. [Shah, Niraj J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY 10029 USA. [Brown, Robert] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1037 BP 715A EP 716A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402360 ER PT J AU Ho, SB Monto, A Peyton, A Kaplan, DE Byrne, S Moon, S Zhu, YN Seyedkazemi, S Rossaro, L Brainard, DM Guyer, W Shaikh, OS Fuchs, M Morgan, TR AF Ho, Samuel B. Monto, Alexander Peyton, Adam Kaplan, David E. Byrne, Sean Moon, Scott Zhu, Yanni Seyedkazemi, Star Rossaro, Lorenzo Brainard, Diana M. Guyer, William Shaikh, Obaid S. Fuchs, Michael Morgan, Timothy R. TI Twelve Weeks of Sofosbuvir plus Ribavirin is Effective for Treatment of Genotype 2 HCV in Difficult to Treat US Veterans with Cirrhosis - Results of the VALOR-HCV Study SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Ho, Samuel B.] VA San Diego Healthcare Syst, Gastroenterol, San Diego, CA USA. [Monto, Alexander] UCSF SFVAMC, Gastroenterol, San Francisco, CA USA. [Peyton, Adam] Miami VA Healthcare Syst, Gastroenterol, Miami, FL USA. [Kaplan, David E.] Philadelphia VA Med Ctr, Gastroenterol, Philadelphia, PA USA. [Byrne, Sean; Moon, Scott; Zhu, Yanni; Seyedkazemi, Star; Rossaro, Lorenzo; Brainard, Diana M.; Guyer, William] Gilead Sci, Foster City, CA USA. [Shaikh, Obaid S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Fuchs, Michael] Richmond VA Med Ctr, Richmond, VA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol, Long Beach, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1041 BP 718A EP 718A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402364 ER PT J AU Basu, P Shah, NJ John, N Aloysius, M Brown, R AF Basu, Patrick Shah, Niraj J. John, Nimy Aloysius, M. Brown, Robert TI Sofosbuvir and Ledipasvir versus Sofosbuvir and Simeprevir combination therapy in the management of acute hepatitis C: A randomized open label prospective clinical pilot study. SLAM C study. Interim data SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Basu, Patrick] Columbia Univ, Sch Phys & Surg, Forest Hills, NY USA. [Basu, Patrick; John, Nimy; Aloysius, M.] Kings Cty Hosp Med Ctr, New York, NY USA. [Shah, Niraj J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY 10029 USA. [Brown, Robert] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1074 BP 736A EP 736A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402396 ER PT J AU Basu, P Shah, NJ John, N Aloysius, M Brown, R AF Basu, Patrick Shah, Niraj J. John, Nimy Aloysius, M. Brown, Robert TI Sofosbuvir, Ledipasvir in IBD treated patients with advanced biologics including Ribavirin eradicating Chronic Hepatitis C: SOLATAIRE C Trial. A multi-center clinical prospective pilot study SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Basu, Patrick] Columbia Univ, Sch Phys & Surg, Forest Hills, NY USA. [Basu, Patrick; John, Nimy; Aloysius, M.] Kings Cty Hosp Med Ctr, New York, NY USA. [Shah, Niraj J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY 10029 USA. [Brown, Robert] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1075 BP 737A EP 737A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402397 ER PT J AU Naggie, S Marks, KM Hughes, M Fierer, DS Kim, AY Hollabaugh, K Kiser, J Roa, J Symonds, B Brainard, DM McHutchison, JG Peters, MG Chung, RT AF Naggie, Susanna Marks, Kristen M. Hughes, Michael Fierer, Daniel S. Kim, Arthur Y. Hollabaugh, Kimberly Kiser, Jennifer Roa, Jhoanna Symonds, Bill Brainard, Diana M. McHutchison, John G. Peters, Marion G. Chung, Raymond T. TI Sofosbuvir Plus Ribavirin Without Interferon For Treatment of Acute Hepatitis C Virus Infection in HIV-1 infected Individuals (SWIFT-C) SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Naggie, Susanna] Duke Univ, Med Ctr, Durham, NC USA. [Marks, Kristen M.] Weill Cornell, New York, NY USA. [Hughes, Michael; Hollabaugh, Kimberly; Roa, Jhoanna] Harvard, Cambridge, MA USA. [Fierer, Daniel S.] Mt Sinai Sch Med, New York, NY USA. [Kim, Arthur Y.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kiser, Jennifer] Univ Colorado, Denver, CO 80202 USA. [Symonds, Bill] Roivant, New York, NY USA. [Brainard, Diana M.; McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Peters, Marion G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1094 BP 748A EP 748A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402416 ER PT J AU Su, F Yu, L Berry, K Liou, IW Landis, CS Reyes, J Rayhill, SC Ioannou, GN AF Su, Feng Yu, Lei Berry, Kristin Liou, Iris W. Landis, Charles S. Reyes, Jorge Rayhill, Stephen C. Ioannou, George N. TI Aging of liver transplant registrants and recipients: trends and impact on waiting list and post-transplantation outcomes SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Su, Feng; Yu, Lei; Liou, Iris W.; Landis, Charles S.; Reyes, Jorge; Rayhill, Stephen C.; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Berry, Kristin; Ioannou, George N.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1211 BP 808A EP 809A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403005 ER PT J AU Feldbrugge, L Mitsuhashi, S Csizmadia, E Sun, XF Schmelzle, M Robson, SC AF Feldbruegge, Linda Mitsuhashi, Shuji Csizmadia, Eva Sun, Xiaofeng Schmelzle, Moritz Robson, Simon C. TI Expression of ENTPD1/CD39 is protective in a mouse model of biliary fibrosis SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Feldbruegge, Linda; Mitsuhashi, Shuji; Csizmadia, Eva; Sun, Xiaofeng; Robson, Simon C.] BIDMC, Gastroenterol, Boston, MA USA. [Schmelzle, Moritz] Charite, Dept Surg, Berlin, Germany. [Feldbruegge, Linda] Univ Hosp Leipzig, Dept Surg, Leipzig, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1394 BP 892A EP 892A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403187 ER PT J AU Shao, B Wakefield, D Baffy, G Karagozian, R AF Shao, Benjamin Wakefield, Dorothy Baffy, Gyorgy Karagozian, Raffi TI Obesity Paradox: Obesity is associated with lower risk of inpatient mortality in patients with cirrhosis, Nationwide Inpatient Sample SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Shao, Benjamin; Karagozian, Raffi] Univ Connecticut, Sch Med, Farmington, CT USA. [Wakefield, Dorothy] UConn Hlth, Ctr Publ Hlth & Hlth Policy, Farmington, CT USA. [Baffy, Gyorgy] VA Boston Healthcare Syst, Gastroenterol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1469 BP 927A EP 927A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403261 ER PT J AU Cai, DC Hong, J Liu, X Lee, SH Fusco, D Schaefer, EA Brisac, C Lidofsky, A Lin, WY Chung, RT AF Cai, Dachuan Hong, Jian Liu, Xiao Lee, Sae Hwan Fusco, Dahlene Schaefer, Esperance A. Brisac, Cynthia Lidofsky, Anna Lin, Wenyu Chung, Raymond T. TI GORASP2 regulates HCV and HBV through RNA and/or DNA replication and virion trafficking SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Cai, Dachuan; Hong, Jian; Liu, Xiao; Lee, Sae Hwan; Fusco, Dahlene; Schaefer, Esperance A.; Brisac, Cynthia; Lidofsky, Anna; Lin, Wenyu; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Cai, Dachuan] Chongqing Med Univ, Affiliated Hosp 2, Dept Infect Dis, Chongqing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1630 BP 1003A EP 1004A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403422 ER PT J AU Lin, WY Cai, DC Hong, J Liu, X Zhao, H Zhu, CL Fusco, D Schaefer, EA Brisac, C Lee, SH Lidofsky, A Chung, RT AF Lin, Wenyu Cai, Dachuan Hong, Jian Liu, Xiao Zhao, Hong Zhu, Chuanlong Fusco, Dahlene Schaefer, Esperance A. Brisac, Cynthia Lee, Sae Hwan Lidofsky, Anna Chung, Raymond T. TI The mechanism of interferon stimulated gene MX1 regulation of HBV and HCV SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Lin, Wenyu; Cai, Dachuan; Hong, Jian; Liu, Xiao; Zhao, Hong; Zhu, Chuanlong; Fusco, Dahlene; Schaefer, Esperance A.; Brisac, Cynthia; Lee, Sae Hwan; Lidofsky, Anna; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Cai, Dachuan] Chongqing Med Univ, Affiliated Hosp 2, Dept Infect Dis, Chongqing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1644 BP 1010A EP 1011A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403436 ER PT J AU Adler, JT Bababekov, Y Markmann, JF Chang, DC Yeh, H AF Adler, Joel T. Bababekov, Yanik Markmann, James F. Chang, David C. Yeh, Heidi TI Distance Affects Mortality on the Waitlist in Pediatric Liver Transplantation SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Adler, Joel T.; Bababekov, Yanik; Markmann, James F.; Chang, David C.; Yeh, Heidi] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1732 BP 1053A EP 1053A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403524 ER PT J AU Mannem, A Rogal, SS Sharma, V Francis, F Cacciarelli, TV Shaikh, OS AF Mannem, Arun Rogal, Shari S. Sharma, Vivek Francis, Fadi Cacciarelli, Thomas V. Shaikh, Obaid S. TI Oral Interferon-free Antiviral Regimens in Liver Transplant Recipients with Hepatitis C: a Real Life Experience SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Mannem, Arun; Shaikh, Obaid S.] Univ Pittsburgh, Sch Med, Med Gastroenterol, Pittsburgh, PA USA. [Mannem, Arun; Rogal, Shari S.; Sharma, Vivek; Francis, Fadi; Cacciarelli, Thomas V.; Shaikh, Obaid S.] Vet Affairs Pittsburgh Healthcare Syst, Med Gastroenterol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1753 BP 1063A EP 1064A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403545 ER PT J AU Davis, BC Tillman, H Fontana, RJ Reddy, KR Chung, RT McGuire, BM Stravitz, RT Lee, WM AF Davis, Brian C. Tillman, Holly Fontana, Robert J. Reddy, K. Rajender Chung, Raymond T. McGuire, Brendan M. Stravitz, R. Todd Lee, William M. TI Heat Stroke Leading to Acute Liver Failure: Case Series from the Acute Liver Failure Study Group SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Davis, Brian C.; Lee, William M.] UT Southwestern Med Ctr, Div Digest & Liver Dis, Dallas, TX USA. [Tillman, Holly] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Fontana, Robert J.] Univ Michigan Hlth Syst, Div Gastroenterol, Ann Arbor, MI USA. [Reddy, K. Rajender] Univ Penn, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [McGuire, Brendan M.] UAB Sch Med, Div Gastroenterol & Hepatol, Birmingham, AL USA. [Stravitz, R. Todd] VCU Med Ctr, Div Gastroenterol, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1768 BP 1070A EP 1071A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404015 ER PT J AU Wei, L Moaven, O Harriman, G Greenwood, JR Bhat, SP Westlin, W Harwood, HJ Kapeller, R Tanabe, KK Fuchs, BC AF Wei, Lan Moaven, Omeed Harriman, Geraldine Greenwood, Jeremy R. Bhat, Sathesh P. Westlin, William Harwood, H. James Kapeller, Rosana Tanabe, Kenneth K. Fuchs, Bryan C. TI Liver Selective Acetyl-CoA Carboxylase Inhibitor ND-654 Improves Sorafenib Efficacy in the Treatment of Hepatocellular Carcinoma in Cirrhotic Rats SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Wei, Lan; Moaven, Omeed; Tanabe, Kenneth K.; Fuchs, Bryan C.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Harriman, Geraldine; Westlin, William; Harwood, H. James; Kapeller, Rosana] Nimbus Therapeut, Cambridge, MA USA. [Greenwood, Jeremy R.; Bhat, Sathesh P.] Schrodinger, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1938 BP 1153A EP 1153A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404183 ER PT J AU Gjuka, D Song, XL Yoo, W Yoo, SY Wang, J Fallon, MB Ioannou, GN Harrison, SA Beretta, L AF Gjuka, Donjeta Song, Xiaoling Yoo, Wonbeak Yoo, Suk Young Wang, Jing Fallon, Michael B. Ioannou, George N. Harrison, Stephen A. Beretta, Laura TI Non-invasive Diagnosis of Non-alcoholic Steatohepatitis (NASH) using a Panel of Fatty Acids SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Gjuka, Donjeta; Yoo, Wonbeak; Beretta, Laura] Univ Texas MD Anderson Canc Ctr, Mol & Cellular Oncol, Houston, TX 77030 USA. [Song, Xiaoling] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Yoo, Suk Young; Wang, Jing] Univ Texas MD Anderson Canc Ctr, Bioinformat & Computat Biol, Houston, TX 77030 USA. [Fallon, Michael B.] Univ Texas MD Anderson Canc Ctr, Div Gastroenterol, Houston, TX 77030 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA. [Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Harrison, Stephen A.] Brooke Army Med Ctr, Dept Med, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2151 BP 1255A EP 1256A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404393 ER PT J AU Corey, KE Gawrieh, S Delemos, A Zheng, H Sanchez, J Danford, CJ Comerford, M Bossi, K Munir, S Chalasani, NP Wattacheril, JJ AF Corey, Kathleen E. Gawrieh, Samer Delemos, Andrew Zheng, Hui Sanchez, Jorge Danford, Christopher J. Comerford, Megan Bossi, Krista Munir, Samina Chalasani, Naga P. Wattacheril, Julia J. TI Risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis due to NAFLD: A multicenter, case- control study SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Corey, Kathleen E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Corey, Kathleen E.; Zheng, Hui; Sanchez, Jorge; Danford, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. [Gawrieh, Samer; Comerford, Megan; Chalasani, Naga P.] Indiana Univ Sch Med, Div Gastroenterol Hepatol, Indianapolis, IN 46202 USA. [Delemos, Andrew; Bossi, Krista] Carolinas Med Ctr, Div Hepatol, Charlotte, NC 28203 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Sanchez, Jorge; Danford, Christopher J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Munir, Samina] Columbia Univ, Med Ctr, Ctr Liver Dis & Transplantat, New York, NY USA. [Wattacheril, Julia J.] Columbia Univ, Coll Phys & Surg, Dept Med, Div Digest & Liver Dis, New York, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2166 BP 1263A EP 1264A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404408 ER PT J AU Long, MT Pedley, A Massaro, JM Hoffmann, U Fox, CS AF Long, Michelle T. Pedley, Alison Massaro, Joseph M. Hoffmann, Udo Fox, Caroline S. TI Non-invasive hepatic fibrosis markers and cardiometabolic risk among adults in the Framingham Heart Study SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Long, Michelle T.] Boston Med Ctr, Gastroenterol, Boston, MA USA. [Long, Michelle T.; Pedley, Alison; Massaro, Joseph M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Biostat, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Endocrinol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2191 BP 1276A EP 1276A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404432 ER PT J AU Corey, KE Kartoun, U Zheng, H Shaw, S AF Corey, Kathleen E. Kartoun, Uri Zheng, Hui Shaw, Stanley TI Identification of Unique Markers of Cardiovascular Disease in NAFLD SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Corey, Kathleen E.; Kartoun, Uri; Zheng, Hui; Shaw, Stanley] Harvard Univ, Sch Med, Boston, MA USA. [Kartoun, Uri; Shaw, Stanley] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Corey, Kathleen E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2194 BP 1277A EP 1277A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404435 ER PT J AU Kleimola, LB Patel, AB Borkar, JA Hibberd, PL AF Kleimola, Lauren B. Patel, Archana B. Borkar, Jitesh A. Hibberd, Patricia L. TI Consequences of household air pollution on child survival: evidence from demographic and health surveys in 47 countries SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE Biomass; Child mortality; Cooking fuel; Household air pollution; Indoor air pollution; Neonatal mortality; Low and middle income countries; Solid fuels ID POLYCYCLIC AROMATIC-HYDROCARBONS; LOWER RESPIRATORY-INFECTIONS; UPDATED SYSTEMATIC ANALYSIS; LOW-BIRTH-WEIGHT; SOLID-FUEL USE; UNDER-5 MORTALITY; BIOMASS FUEL; RISK; PNEUMONIA; INFANT AB Background: Over one-third of the world's population is exposed to household air pollution (HAP) but the separate effects of cooking with solid fuel and kerosene on childhood mortality are unclear. Objectives: To evaluate the effects of both solid fuels and kerosene on neonatal (0-28 days) and child (29 days-59 months) mortality. Methods: We used Demographic and Health Surveys from 47 countries and calculated adjusted relative risks (aRR) using Poisson regression models. Results: The aRR of neonatal and child mortality in households exposed to solid fuels were 1.24 (95% CI: 1.14, 1.34) and 1.21 (95% CI: 1.12, 1.30), respectively, and the aRR for neonatal and child mortality in households exposed to kerosene were 1.34 (95% CI: 1.18, 1.52) and 1.12 (95% CI: 0.99, 1.27), controlling for individual, household, and country-level predictors of mortality. Conclusions: Kerosene should not be classified as a clean fuel. Neonates are at risk for mortality from exposure to solid fuels and kerosene. C1 [Kleimola, Lauren B.; Hibberd, Patricia L.] Massachusetts Gen Hosp, Div Global Hlth, Dept Pediat, Boston, MA 02114 USA. [Patel, Archana B.; Borkar, Jitesh A.] Kinkinie Grover Mem Charitable Trust, Lata Med Res Fdn, Nagpur, Maharashtra, India. [Patel, Archana B.] Indira Gandhi Govt Med Coll, Dept Pediat, Nagpur, Maharashtra, India. RP Kleimola, LB (reprint author), Massachusetts Gen Hosp, MPH, Boston, MA 02114 USA. EM lkleimola@mgh.harvard.edu NR 36 TC 3 Z9 3 U1 1 U2 8 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1077-3525 EI 2049-3967 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD OCT PY 2015 VL 21 IS 4 BP 294 EP 302 DI 10.1179/2049396715Y.0000000007 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DB1HL UT WOS:000368259000003 PM 25843087 ER PT J AU Kovacs, K Marra, KV Yu, GN Wagley, S Ma, J Teague, GC Nandakumar, N Lashkari, K Arroyo, JG AF Kovacs, Kyle Marra, Kyle V. Yu, Gina Wagley, Sushant Ma, Jie Teague, Gianna C. Nandakumar, Namrata Lashkari, Kameran Arroyo, Jorge G. TI Angiogenic and Inflammatory Vitreous Biomarkers Associated With Increasing Levels of Retinal Ischemia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE retinal ischemia; angiogenic; inflammatory; vitreous; neovascular glaucoma ID ENDOTHELIAL GROWTH-FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY; HIGH-AFFINITY BINDING; NEOVASCULAR GLAUCOMA; INTRAVITREAL BEVACIZUMAB; AQUEOUS-HUMOR; REPERFUSION INJURY; VEIN OCCLUSION; MACULAR EDEMA; FACTOR-I AB PURPOSE. To characterize the angiogenic and inflammatory vitreous biomarker profiles in a spectrum of ischemic retinopathies, including neovascular glaucoma. METHODS. This institutional review board-approved study retrospectively analyzed 80 undiluted vitreous samples obtained during pars vitrectomy. The specimens were frozen (-80 degrees C) and sent for concentration analysis of 34 proteins by Bio-Plex Pro assays. Specimens were divided into four groups: patients undergoing epiretinal membrane (ERM) peeling and/or macular hole (MH) surgery with no history of diabetes (non-DM group), patients undergoing ERM peeling, and/or MH surgery with a history of diabetes (DM group), patients with proliferative diabetic retinopathy (PDR group), and patients with neovascular glaucoma (NVG group). Parametric and nonparametric analyses of demographics and cytokine levels were performed using SPSS. RESULTS. There were no significant differences in demographics among cohorts. Numerous proteins were significantly elevated between non-DM and DM (G-CSF, sCD40L, Endoglin, IL-6, placental growth factor [PlGF], VEGF-D), DM and PDR (leptin, IL-8, PlGF, VEGF-A), and PDR and NVG (G-CSF, leptin, TIE-2, sCD40L, EGF, HB-EGF, IL-6, IL-8, PlGF, TNF-alpha). Only PlGF was significantly elevated between each successive cohort. The most potent drivers of NVG were PlGF, VEGF-A, IL-6, and IL-8. CONCLUSIONS. While the role of angioproliferative growth factors is well documented in ischemic retinopathy, our study delineates the importance of inflammatory and previously underreported angiogenic proteins. It also demonstrates a significant incremental increase in certain factors with increasing levels of ischemia. Both of these findings may guide the development of future therapies for ischemic retinopathies. C1 [Kovacs, Kyle] Yale Univ, Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06510 USA. [Marra, Kyle V.] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Yu, Gina; Wagley, Sushant; Arroyo, Jorge G.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. [Ma, Jie; Teague, Gianna C.; Nandakumar, Namrata; Lashkari, Kameran] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Arroyo, JG (reprint author), Beth Israel Deaconess Med Ctr, Retina Serv, Div Ophthalmol, 330 Brookline Ave,Shapiro 5th Floor, Boston, MA 02215 USA. EM jarroyo@bidmc.harvard.edu NR 58 TC 4 Z9 5 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2015 VL 56 IS 11 BP 6523 EP 6530 DI 10.1167/iovs.15-16793 PG 8 WC Ophthalmology SC Ophthalmology GA DB0YQ UT WOS:000368235100041 PM 26447988 ER PT J AU Kang, JH Loomis, SJ Rosner, BA Wiggs, JL Pasquale, LR AF Kang, Jae H. Loomis, Stephanie J. Rosner, Bernard A. Wiggs, Janey L. Pasquale, Louis R. TI Author Response: Comparison of Risk Factor Profiles for Primary Open-Angle Glaucoma Subtypes Defined by Pattern of Visual Field Loss: True Risk Factors or Arbituary Definition? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Letter ID PARAFOVEAL C1 [Kang, Jae H.; Rosner, Bernard A.; Pasquale, Louis R.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Kang, Jae H.; Rosner, Bernard A.; Pasquale, Louis R.] Harvard Univ, Sch Med, Boston, MA USA. [Loomis, Stephanie J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Rosner, Bernard A.] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Wiggs, Janey L.; Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Kang, JH (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. EM nhjhk@channing.harvard.edu NR 16 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2015 VL 56 IS 11 BP 6532 EP 6533 DI 10.1167/iovs.15-17944 PG 2 WC Ophthalmology SC Ophthalmology GA DB0YQ UT WOS:000368235100043 PM 26451681 ER PT J AU Cruzat, A Schrems, WA Schrems-Hoesl, LM Cavalcanti, BM Baniasadi, N Witkin, D Pavan-Langston, D Dana, R Hamrah, P AF Cruzat, Andrea Schrems, Wolfgang A. Schrems-Hoesl, Laura M. Cavalcanti, Bernardo M. Baniasadi, Neda Witkin, Deborah Pavan-Langston, Deborah Dana, Reza Hamrah, Pedram TI Contralateral Clinically Unaffected Eyes of Patients With Unilateral Infectious Keratitis Demonstrate a Sympathetic Immune Response SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE microbial keratitis; in vivo confocal microscopy; dendritic cells; corneal nerves; contralateral ID VIVO-CONFOCAL-MICROSCOPY; ANTIGEN-PRESENTING CELLS; GENE-RELATED PEPTIDE; CONTACT-LENS WEARERS; IN-VIVO; CORNEAL NERVES; DENDRITIC CELLS; NERVOUS-SYSTEM; SUBSTANCE-P; INFLAMMATION AB PURPOSE. To analyze the contralateral unaffected eyes of patients with microbial keratitis (MK) for any immune cell or nerve changes by laser in vivo confocal microscopy (IVCM). METHODS. A prospective study was performed on 28 patients with MK, including acute bacterial, fungal, and Acanthamoeba keratitis, as well as on their contralateral clinically unaffected eyes and on control groups, which consisted of 28 age-matched normal controls and 15 control contact lens (CL) wearers. Laser IVCM with the Heidelberg Retinal Tomograph 3/Rostock Cornea Module and Cochet-Bonnet esthesiometry of the central cornea were performed. Two masked observers assessed central corneal dendritiform cell density and subbasal corneal nerve parameters. RESULTS. The contralateral clinically unaffected eyes of patients with MK demonstrated significant diminishment in nerve density (15,603.8 +/- 1265.2 vs. 24,102.1 +/- 735.6 mu m/mm(2)), total number of nerves (11.9 +/- 1.0 vs. 24.9 +/- 1.2/frame), number of branches (1.7 6 0.2 vs. 19.9 +/- 1.3/frame), and branch nerve length (5775.2 +/- 757.1 vs. 12,715.4 +/- 648.4 mu m/mm(2)) (P < 0.001 for all parameters) compared to normal controls and CL wearers. Further, dendritiform cell density in the contralateral unaffected eyes was significantly increased as compared to that in controls (117.5 +/- 19.9 vs. 24.2 +/- 3.5 cells/mm(2), P < 0.001). CONCLUSIONS. We demonstrate a subclinical involvement in the contralateral clinically unaffected eyes in patients with unilateral acute MK. In vivo confocal microscopy reveals not only a diminishment of the subbasal corneal nerves and sensation, but also an increase in dendritiform cell density in the contralateral unaffected eyes of MK patients. These findings show bilateral immune alterations in a clinically unilateral disease. C1 [Cruzat, Andrea; Schrems, Wolfgang A.; Schrems-Hoesl, Laura M.; Cavalcanti, Bernardo M.; Baniasadi, Neda; Witkin, Deborah; Pavan-Langston, Deborah; Dana, Reza; Hamrah, Pedram] Harvard Univ, Sch Med, Ocular Surface Imaging Ctr, Boston, MA USA. [Cruzat, Andrea; Schrems, Wolfgang A.; Schrems-Hoesl, Laura M.; Cavalcanti, Bernardo M.; Baniasadi, Neda; Witkin, Deborah; Pavan-Langston, Deborah; Dana, Reza; Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv,Dept Ophthalmol, Boston, MA USA. [Cruzat, Andrea] Pontificia Univ Catolica Chile, Dept Ophthalmol, Santiago, Chile. [Hamrah, Pedram] Tufts Univ, Sch Med, Boston Image Reading Ctr, Boston, MA 02111 USA. [Hamrah, Pedram] Tufts Univ, Sch Med, New England Eye Ctr, Cornea Serv,Dept Ophthalmol,Tufts Med Ctr, Boston, MA 02111 USA. RP Hamrah, P (reprint author), Tufts Med Ctr, Dept Ophthalmol, Boston, MA 02111 USA. EM phamrah@tuftsmedicalcenter.org FU NEI NIH HHS [K08 EY020575, K08-EY020575, K24 EY019098, K24-EY19098, R01 EY022695, R01-EY022695] NR 43 TC 4 Z9 4 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2015 VL 56 IS 11 BP 6612 EP 6620 DI 10.1167/iovs.15-16560 PG 9 WC Ophthalmology SC Ophthalmology GA DB0YQ UT WOS:000368235100053 PM 26465889 ER PT J AU Maidana, DE Tsoka, P Tian, B Dib, B Matsumoto, H Kataoka, K Lin, HJ Miller, JW Vavvas, DG AF Maidana, Daniel E. Tsoka, Pavlina Tian, Bo Dib, Bernard Matsumoto, Hidetaka Kataoka, Keiko Lin, Haijiang Miller, Joan W. Vavvas, Demetrios G. TI A Novel ImageJ Macro for Automated Cell Death Quantitation in the Retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE cell death; inner nuclear layer; NMDA; outer nuclear layer; retina; retinal detachment; TUNEL assay ID DNA FRAGMENTATION; IN-SITU; IDENTIFICATION; NECROPTOSIS; APOPTOSIS; NECROSIS AB PURPOSE. TUNEL assay is widely used to evaluate cell death. Quantification of TUNEL-positive (TUNEL+) cells in tissue sections is usually performed manually, ideally by two masked observers. This process is time consuming, prone to measurement errors, and not entirely reproducible. In this paper, we describe an automated quantification approach to address these difficulties. METHODS. We developed an ImageJ macro to quantitate cell death by TUNEL assay in retinal cross-section images. The script was coded using IJ1 programming language. To validate this tool, we selected a dataset of TUNEL assay digital images, calculated layer area and cell count manually (done by two observers), and compared measurements between observers and macro results. RESULTS. The automated macro segmented outer nuclear layer (ONL) and inner nuclear layer (INL) successfully. Automated TUNEL+ cell counts were in-between counts of inexperienced and experienced observers. The intraobserver coefficient of variation (COV) ranged from 13.09% to 25.20%. The COV between both observers was 51.11 +/- 25.83% for the ONL and 56.07 +/- 24.03% for the INL. Comparing observers' results with macro results, COV was 23.37 +/- 15.97% for the ONL and 23.44 +/- 18.56% for the INL. CONCLUSIONS. We developed and validated an ImageJ macro that can be used as an accurate and precise quantitative tool for retina researchers to achieve repeatable, unbiased, fast, and accurate cell death quantitation. We believe that this standardized measurement tool could be advantageous to compare results across different research groups, as it is freely available as open source. C1 [Maidana, Daniel E.; Tsoka, Pavlina; Tian, Bo; Dib, Bernard; Matsumoto, Hidetaka; Kataoka, Keiko; Lin, Haijiang; Miller, Joan W.; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab, Boston, MA USA. RP Vavvas, DG (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Demetrios_Vavvas@MEEI.HARVARD.EDU RI Kataoka, Keiko/B-2806-2016 OI Kataoka, Keiko/0000-0002-8795-6536 FU NEI NIH HHS [R01 EY025362, P30 EY014104, R21 EY023079, EY014104, R21EY023079-01A1] NR 20 TC 1 Z9 1 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2015 VL 56 IS 11 BP 6701 EP 6708 DI 10.1167/iovs.15-17599 PG 8 WC Ophthalmology SC Ophthalmology GA DB0YQ UT WOS:000368235100067 PM 26469755 ER PT J AU Heindl, LM Kaser-Eichberger, A Schlereth, SL Bock, F Regenfuss, B Reitsamer, HA McMenamin, P Lutty, GA Maruyama, K Chen, L Dana, R Kerjaschki, D Alitalo, K De Stefano, ME Junghans, BM Schroedl, F Cursiefen, C AF Heindl, Ludwig M. Kaser-Eichberger, Alexandra Schlereth, Simona L. Bock, Felix Regenfuss, Birgit Reitsamer, Herbert A. McMenamin, Paul Lutty, Gerard A. Maruyama, Kazuichi Chen, Lu Dana, Reza Kerjaschki, Dontscho Alitalo, Kari De Stefano, Maria Egle Junghans, Barbara M. Schroedl, Falk Cursiefen, Claus TI Sufficient Evidence for Lymphatics in the Developing and Adult Human Choroid? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Letter ID TRANSCRIPTION FACTOR; ENDOTHELIAL-CELLS; HUMAN TISSUES; EXPRESSION; PROX1; MARKERS; VESSELS; VASCULATURE; PODOPLANIN; MORPHOLOGY C1 [Heindl, Ludwig M.; Schlereth, Simona L.; Bock, Felix; Regenfuss, Birgit; Cursiefen, Claus] Univ Cologne, Dept Ophthalmol, D-50931 Cologne, Germany. [Kaser-Eichberger, Alexandra; Reitsamer, Herbert A.; Schroedl, Falk] Paracelsus Med Univ, Dept Ophthalmol, Salzburg, Austria. [McMenamin, Paul] Monash Univ, Dept Anat & Dev Biol, Fac Med Nursing & Hlth Sci, Melbourne, Vic 3004, Australia. [Lutty, Gerard A.] Johns Hopkins Univ, Wilmer Ophthalmol Inst, Baltimore, MD 21218 USA. [Maruyama, Kazuichi] Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Sendai, Miyagi 980, Japan. [Chen, Lu] Univ Calif Berkeley, Ctr Eye Dis & Dev, Program Vis Sci, Berkeley, CA 94720 USA. [Chen, Lu] Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA. [Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Kerjaschki, Dontscho] Med Univ Vienna, Dept Pathol, Vienna, Austria. [Alitalo, Kari] Univ Helsinki, Inst Biomed, Helsinki, Finland. [De Stefano, Maria Egle] Univ Roma La Sapienza, Fdn Cenci Bolognetti, Ist Pasteur, Dept Biol & Biotechnol Charles Darwin, I-00185 Rome, Italy. [Junghans, Barbara M.] Univ New S Wales, Sch Optometry & Vis Sci, Sydney, NSW, Australia. [Schroedl, Falk] Paracelsus Med Univ, Dept Anat, Salzburg, Austria. RP Heindl, LM (reprint author), Univ Cologne, Dept Ophthalmol, D-50931 Cologne, Germany. EM ludwig.heindl@uk-koeln.de OI Junghans, Barbara/0000-0002-2089-7965 FU NEI NIH HHS [R01 EY017392] NR 30 TC 1 Z9 1 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2015 VL 56 IS 11 BP 6709 EP 6710 DI 10.1167/iovs.15-17686 PG 2 WC Ophthalmology SC Ophthalmology GA DB0YQ UT WOS:000368235100068 PM 26588256 ER PT J AU Batki, SL AF Batki, Steven L. TI What Is the Right Pharmacotherapy for Alcohol Use Disorder in Patients With Schizophrenia? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material DE Antipsychotics; Comorbidity; Schizophrenia; Substance-Related Disorders ID SUBSTANCE USE DISORDER; NALTREXONE; DEPENDENCE C1 [Batki, Steven L.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94121 USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Batki, SL (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Psychiat, 4150 Clement St, San Francisco, CA 94121 USA. EM steven.batki@ucsf.edu FU NIH/NIAAA [RO1 AA013655]; Department of Defense [W81XWH-12-2-0137, W81XWH-11-2-0245] FX This work was supported in part by NIH/NIAAA Grant RO1 AA013655 and Department of Defense Grants W81XWH-12-2-0137 and W81XWH-11-2-0245 and with the support of the resources of the San Francisco Veterans Affairs Medical Center. NR 10 TC 0 Z9 0 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2015 VL 76 IS 10 BP E1336 EP E1337 DI 10.4088/JCP.14com09611 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DB2OC UT WOS:000368347900018 PM 26528663 ER PT J AU Okello, S Kanyesigye, M Muyindike, WR Annex, BH Hunt, PW Haneuse, S Siedner, MJ AF Okello, Samson Kanyesigye, Michael Muyindike, Winnie R. Annex, Brian Herb Hunt, Peter W. Haneuse, Sebastien Siedner, Mark Jacob TI Incidence and predictors of hypertension in adults with HIV-initiating antiretroviral therapy in south-western Uganda SO JOURNAL OF HYPERTENSION LA English DT Article DE aging; antiretroviral therapy; HIV; AIDS; hypertension; noncommunicable disease; sub-Saharan Africa ID IMMUNODEFICIENCY-VIRUS-INFECTION; FRAMINGHAM RISK SCORE; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; INCOME COUNTRIES; LIFE EXPECTANCY; CELL COUNT; COHORT; STROKE; MEN AB Objective:The successful scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has led to increasing life expectancy, and thus increased risk of hypertension. We aimed to describe the incidence and predictors of hypertension in HIV patients receiving ART at a publicly funded clinic in rural Uganda.Methods:We abstracted data from medical records of adult patients who initiated ART at an HIV clinic in south-western Uganda during 2010-2012. We defined hypertension as at least two consecutive clinical visits, with a SBP at least 140 mmHg and/or SBP of at least 90 mmHg, or prescription for an antihypertensive medication. We calculated the incidence of hypertension and fit multivariable Cox proportional-hazards models to identify predictors of hypertension.Results:A total of 3389 patients initiated ART without a prior diagnosis of hypertension during the observation period. Over 3990 person-years of follow-up, 445 patients developed hypertension, for a crude incidence of 111.5/1000 (95% confidence interval 101.9-121.7) person-years. Rates were highest among men aged at least 40 years (158.8per/1000 person-years) and lowest in women aged 30-39 years (80/1000 person-years). Lower CD4(+) cell count at ART initiation, as well as traditional risk factors including male sex, increasing age, and obesity, were independently associated with hypertension.Conclusion:We observed a high incidence of hypertension in HIV-infected persons on ART in rural Uganda, and increased risk with lower nadir CD4(+) cell counts. Our findings call for increased attention to screening of and treatment for hypertension, along with continued prioritization of early ART initiation. C1 [Okello, Samson; Muyindike, Winnie R.] Mbarara Reg Referral Hosp, Dept Internal Med, Mbarara, Uganda. [Kanyesigye, Michael; Muyindike, Winnie R.] Mbarara Reg Referral Hosp, Immune Suppress Syndrome Clin, Mbarara, Uganda. [Annex, Brian Herb] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA USA. [Annex, Brian Herb] Univ Virginia, Dept Med, Div Cardiovasc Med, Charlottesville, VA USA. [Hunt, Peter W.] Univ Calif San Francisco, Dept Med, Div HIV AIDS, San Francisco, CA USA. [Okello, Samson] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Haneuse, Sebastien] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Siedner, Mark Jacob] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Siedner, Mark Jacob] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Siedner, Mark Jacob] Harvard Univ, Sch Med, Boston, MA USA. RP Okello, S (reprint author), Mbarara Univ Sci & Technol, Dept Internal Med, POB 1410, Mbarara, Uganda. EM Okello.samson@must.ac.ug OI Okello, Samson/0000-0001-7377-6094 FU Canda-Africa Preventive Trials (CAPT) network mentorship award; National Institutes of Health [NIH K23099916]; Harvard Center for AIDS Research FX S.O. received the Canda-Africa Preventive Trials (CAPT) network 2013 mentorship award to carry out this study. M.J.S. receives research support from the National Institutes of Health (NIH K23099916) and the Harvard Center for AIDS Research. NR 45 TC 10 Z9 10 U1 0 U2 0 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 OCT PY 2015 VL 33 IS 10 BP 2039 EP 2045 DI 10.1097/HJH.0000000000000657 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DB4QE UT WOS:000368497400012 PM 26431192 ER PT J AU Lesenfants, D Chatelle, C Laureys, S Noirhomme, Q AF Lesenfants, Damien Chatelle, Camille Laureys, Steven Noirhomme, Quentin TI Brain-computer interfaces, Locked-In syndrome, and disorders of consciousness SO M S-MEDECINE SCIENCES LA French DT Article ID BEDSIDE DETECTION; VEGETATIVE STATE; AWARENESS; PARADIGM; COHORT AB Detecting signs of consciousness in patients with severe brain injury constitutes a real challenge for clinicians. The current gold standard in clinical diagnosis is the behavioral scale relying on motor abilities, which are often impaired or nonexistent in these patients. In this context, brain-computer interfaces (BCIs) could offer a potential complementary tool to detect signs of consciousness whilst bypassing the usual motor pathway. In addition to complementing behavioral assessments and potentially reducing error rate, BCIs could also serve as a communication tool for paralyzed but conscious patients, e.g., suffering from Locked-In Syndrome. In this paper, we report on recent work conducted by the Coma Science Group on BCI technology, aiming to optimize diagnosis and communication in patients with disorders of consciousness and Locked-In syndrome. C1 [Lesenfants, Damien; Chatelle, Camille; Laureys, Steven; Noirhomme, Quentin] Univ Liege, Coma Sci Grp, Cyclotron Res Ctr, B-4000 Liege, Belgium. [Lesenfants, Damien; Chatelle, Camille; Laureys, Steven; Noirhomme, Quentin] Univ Liege, Dept Neurol, B-4000 Liege, Belgium. [Lesenfants, Damien] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Lesenfants, Damien] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Chatelle, Camille] Massachusetts Gen Hosp, Lab Neuroimaging Coma & Consciousness, Boston, MA 02114 USA. [Chatelle, Camille] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Chatelle, Camille] Harvard Univ, Sch Med, Boston, MA USA. [Noirhomme, Quentin] Brain Innovat BV, Maastricht, Netherlands. RP Lesenfants, D (reprint author), Univ Liege, Coma Sci Grp, Cyclotron Res Ctr, Allee 6 Aout, B-4000 Liege, Belgium. EM damien_lesenfants@brown.edu RI Laureys, Steven/A-3349-2011 NR 30 TC 0 Z9 0 U1 3 U2 8 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD OCT PY 2015 VL 31 IS 10 BP 906 EP 913 DI 10.1051/medsci/20153110017 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DB1FP UT WOS:000368253800017 ER PT J AU Brink, JA Miller, DL AF Brink, James A. Miller, Donald L. TI US National Diagnostic Reference Levels: Closing the Gap SO RADIOLOGY LA English DT Editorial Material C1 [Brink, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Diagnost Radiol, Boston, MA 02114 USA. [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Brink, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Diagnost Radiol, 175 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM jabrink@partners.org NR 22 TC 3 Z9 3 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2015 VL 277 IS 1 BP 3 EP 6 DI 10.1148/radiol.2015150971 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB3TG UT WOS:000368434000002 PM 26115453 ER PT J AU Bredella, MA Daley, SM Kalra, MK Brown, JK Miller, KK Torriani, M AF Bredella, Miriam A. Daley, Scott M. Kalra, Mannudeep K. Brown, J. Keenan Miller, Karen K. Torriani, Martin TI Marrow Adipose Tissue Quantification of the Lumbar Spine by Using Dual-Energy CT and Single-Voxel H-1 MR Spectroscopy: A Feasibility Study SO RADIOLOGY LA English DT Article ID BONE-MINERAL DENSITY; COMPUTED-TOMOGRAPHY; FAT-CONTENT; ANOREXIA-NERVOSA; QUANTITATIVE CT; OSTEOPOROSIS; QCT; ABSORPTIOMETRY; FRAGILITY; ACCURACY AB Purpose: To test the performance of dual-energy computed tomography (CT) in the assessment of marrow adipose tissue (MAT) content of the lumbar spine by using proton (hydrogen 1 [H-1]) magnetic resonance (MR) spectroscopy as a reference standard and to determine the influence of MAT on the assessment of bone mineral density (BMD). Materials and Methods: This study was institutional review board approved and complied with HIPAA guidelines. Written informed consent was obtained. Twelve obese osteopenic but otherwise healthy subjects (mean age 6 standard deviation, 43 years 6 13) underwent 3-T H-1 MR spectroscopy of the L2 vertebra by using a point-resolved spatially localized spectroscopy sequence without water suppression. The L2 vertebra was scanned with dual-energy CT (80 and 140 kV) by using a dual-source multi-detector row CT scanner with a calibration phantom. Mean basis material composition relative to the phantom was estimated in the L2 vertebra. Volumetric BMD was measured with and without correction for MAT. Bland-Altman 95% limits of agreement and Pearson correlation coefficients were calculated. Results: There was excellent agreement between H-1 MR spectroscopy and dual-energy CT, with a mean difference in fat fraction of 20.02 between the techniques, with a 95% confidence interval of 20.24, 0.20. There was a strong correlation between marrow fat fraction obtained with H-1 MR spectroscopy and that obtained with dual-energy CT (r = 0.91, P < .001). The presence of MAT led to underestimation of BMD, and this bias increased with increasing MAT content (P <.001). Conclusion: Dual-energy CT can be used to assess MAT content and BMD of the lumbar spine in a single examination and provides data that closely agree and correlate with 1H MR spectroscopy data. (C) RSNA, 2015 C1 [Bredella, Miriam A.; Daley, Scott M.; Kalra, Mannudeep K.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Brown, J. Keenan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Brown, J. Keenan] Mindways Software, Austin, TX USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM mbredella@partners.org FU NIDDK NIH HHS [P30 DK040561, R01 DK095792] NR 25 TC 6 Z9 6 U1 1 U2 2 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 OCT PY 2015 VL 277 IS 1 BP 230 EP 235 DI 10.1148/radiol.2015142876 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB3TG UT WOS:000368434000029 PM 25988401 ER PT J AU Kennedy, GT Okusanya, OT Keating, JJ Heitjan, DF Deshpande, C Litzky, LA Albelda, SM Drebin, JA Nie, SM Low, PS Singhal, S AF Kennedy, Gregory T. Okusanya, Olugbenga T. Keating, Jane J. Heitjan, Daniel F. Deshpande, Charuhas Litzky, Leslie A. Albelda, Steven M. Drebin, Jeffrey A. Nie, Shuming Low, Philip S. Singhal, Sunil TI The Optical Biopsy: A Novel Technique for Rapid Intraoperative Diagnosis of Primary Pulmonary Adenocarcinomas SO ANNALS OF SURGERY LA English DT Article DE intraoperative diagnosis; optical biopsy; surgical oncology ID EXPRESSION; SURGERY AB Background:With increasing use of chest computed tomography scans, indeterminate pulmonary nodules are frequently detected as an incidental finding and present a diagnostic challenge. Tissue biopsy followed by histological review and immunohistochemistry is the gold standard to obtain a diagnosis and the most common malignant finding is a primary lung adenocarcinoma. Our objective was to determine whether an intraoperative optical biopsy (molecular imaging) may provide an alternative approach for determining if a pulmonary nodule is a primary lung adenocarcinoma.Methods:Before surgery, 30 patients with an indeterminate pulmonary nodule were intravenously administered a folate receptor-targeted fluorescent contrast agent specific for primary lung adenocarcinomas. During surgery, the nodule was removed and the presence of fluorescence (optical biopsy) was assessed in the operating room to determine if the nodule was a primary pulmonary adenocarcinoma. Standard-of-care frozen section and immunohistochemical staining on permanent sections were then performed as the gold standard to validate the results of the optical biopsy.Results:Optical biopsies identified 19 of 19 (100%) primary pulmonary adenocarcinomas. There were no false positive or false negative diagnoses. An optical biopsy required 2.4 minutes compared to 26.5 minutes for frozen section (P<0.001) and it proved more accurate than frozen section in diagnosing lung adenocarcinomas.Conclusions:An optical biopsy has excellent positive predictive value for intraoperative diagnosis of primary lung adenocarcinomas. With refinement, this technology may prove to be an important supplement to standard pathology for examining close surgical margins, identifying lymph node involvement, and determining whether suspicious nodules are malignant. C1 [Kennedy, Gregory T.; Okusanya, Olugbenga T.; Keating, Jane J.; Drebin, Jeffrey A.; Singhal, Sunil] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Kennedy, Gregory T.; Okusanya, Olugbenga T.; Keating, Jane J.; Drebin, Jeffrey A.; Singhal, Sunil] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Heitjan, Daniel F.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Deshpande, Charuhas; Litzky, Leslie A.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Albelda, Steven M.; Singhal, Sunil] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Nie, Shuming] Emory Univ, Dept Biomed Engn, Atlanta, GA 30322 USA. [Nie, Shuming] Emory Univ, Dept Chem, Atlanta, GA 30322 USA. [Low, Philip S.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. RP Singhal, S (reprint author), Hosp Univ Penn, Div Thorac Surg, 6 White Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM Sunil.Singhal@uphs.upenn.edu OI Low, Philip/0000-0001-9042-5528 FU Biomedical Laboratory Research and Development Service of the VA Office of Research and Development [I011CX001189]; National Institutes of Health [P30 CA016520] FX This work was supported by Award Number I011CX001189 (SS, CD) from the Biomedical Laboratory Research and Development Service of the VA Office of Research and Development. This work was also supported by the National Institutes of Health P30 CA016520 (DFH). NR 13 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 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD OCT PY 2015 VL 262 IS 4 BP 602 EP 609 DI 10.1097/SLA.0000000000001452 PG 8 WC Surgery SC Surgery GA DA7QT UT WOS:000367999800006 PM 26366539 ER PT J AU Hameed, M Corless, C George, S Hornick, JL Kakar, S Lazar, AJ Tang, L AF Hameed, Meera Corless, Christopher George, Suzanne Hornick, Jason L. Kakar, Sanjay Lazar, Alexander J. Tang, Laura CA Coll Amer Pathologists TI Template for Reporting Results of Biomarker Testing of Specimens From Patients With Gastrointestinal Stromal Tumors SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SUCCINATE-DEHYDROGENASE; DIFFERENTIAL-DIAGNOSIS; ACTIVATING MUTATIONS; IMATINIB MESYLATE; TYROSINE KINASE; SDHA MUTATIONS; C-KIT; EXPRESSION; MARKER; GISTS C1 [Hameed, Meera; Tang, Laura] Mem Sloan Kettering Canc Ctr, Dept Pathol, Surg Pathol, New York, NY 10065 USA. [Corless, Christopher] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [George, Suzanne] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Kakar, Sanjay] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Lazar, Alexander J.] Univ Texas MD Anderson Canc Ctr, Sarcoma Res Ctr, Dept Pathol, Houston, TX 77030 USA. RP Hameed, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, Surg Pathol, New York, NY 10065 USA. EM hameedm@mskcc.org RI Lazar, Alexander/A-3416-2008 OI Lazar, Alexander/0000-0002-6395-4499 NR 34 TC 0 Z9 0 U1 0 U2 2 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2015 VL 139 IS 10 BP 1271 EP 1275 DI 10.5858/arpa.2014-0578-CP PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA DA1YZ UT WOS:000367593400014 PM 25729899 ER PT J AU Dawes, AJ Sacks, GD Cryer, HG Gruen, JP Preston, C Gorospe, D Cohen, M McArthur, DL Russell, MM Maggard-Gibbons, M Ko, CY AF Dawes, Aaron J. Sacks, Greg D. Cryer, H. Gill Gruen, J. Peter Preston, Christy Gorospe, Deidre Cohen, Marilyn McArthur, David L. Russell, Marcia M. Maggard-Gibbons, Melinda Ko, Clifford Y. CA Los Angeles Cty Trauma Consortium TI Compliance With Evidence-Based Guidelines and Interhospital Variation in Mortality for Patients With Severe Traumatic Brain Injury SO JAMA SURGERY LA English DT Article ID BLOOD-STREAM INFECTIONS; CARE QUALITY MEASURES; INTRACRANIAL-PRESSURE; UNITED-STATES; RELIABILITY ADJUSTMENT; INPATIENT MORTALITY; SURGICAL OUTCOMES; HEAD-INJURY; ASSOCIATION; IMPROVEMENT AB IMPORTANCE Compliance with evidence-based guidelines in traumatic brain injury (TBI) has been proposed as a marker of hospital quality. However, the association between hospital-level compliance rates and risk-adjusted clinical outcomes for patients with TBI remains poorly understood. OBJECTIVE To examine whether hospital-level compliance with the Brain Trauma Foundation guidelines for intracranial pressure monitoring and craniotomy is associated with risk-adjusted mortality rates for patients with severe TBI. DESIGN, SETTING, AND PARTICIPANTS All adult patients (N = 734) who presented to a regional consortium of 14 hospitals from January 1, 2009, through December 31, 2010, with severe TBI (ie, blunt head trauma, Glasgow Coma Scale score of < 9, and abnormal intracranial findings from computed tomography of the head). Data analysis took place from December 2013 through January 2015. We used hierarchical mixed-effects models to assess the association between hospital-level compliance with Brain Trauma Foundation guidelines and mortality rates after adjusting for patient-level demographics, severity of trauma (eg, mechanism of injury and Injury Severity Score), and TBI-specific variables (eg, cranial nerve reflexes and findings from computed tomography of the head). MAIN OUTCOMES AND MEASURES Hospital-level risk-adjusted inpatient mortality rate and hospital-level compliance with Brain Trauma Foundation guidelines for intracranial pressure monitoring and craniotomy. RESULTS Unadjusted mortality rates varied by site from 20.0% to 50.0% (median, 42.6; interquartile range, 35.5-46.2); risk-adjusted rates varied from 24.3% to 56.7% (median, 41.1; interquartile range, 36.4-47.8). Overall, only 338 of 734 patients (46.1%) with an appropriate indication underwent placement of an intracranial pressure monitor and only 134 of 335 (45.6%) underwent craniotomy. Hospital-level compliance ranged from 9.6% to 65.2% for intracranial pressure monitoring and 6.7% to 76.2% for craniotomy. Despite widespread variation in compliance across hospitals, we found no association between hospital-level compliance rates and risk-adjusted patient outcomes (Spearman. = 0.030 [P = .92] for ICP monitoring and Spearman. = -0.066 [P = .83] for craniotomy). CONCLUSIONS AND RELEVANCE Hospital-level compliance with evidence-based guidelines has minimal association with risk-adjusted outcomes in patients with severe TBI. Our results suggest that caution should be taken before using compliance with these measures as independent quality metrics. Given the complexity of TBI care, outcomes-based metrics, including functional recovery, may be more accurate than current process measures at determining hospital quality. C1 [Dawes, Aaron J.; Sacks, Greg D.; Cryer, H. Gill; Cohen, Marilyn; Russell, Marcia M.; Maggard-Gibbons, Melinda; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Sacks, Greg D.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Russell, Marcia M.; Maggard-Gibbons, Melinda; Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Gruen, J. Peter] Univ So Calif, Dept Neurosurg, Los Angeles, CA USA. [Preston, Christy; Gorospe, Deidre] Cty Los Angeles Dept Hlth Serv, Emergency Med Serv Agcy, Los Angeles, CA USA. [McArthur, David L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA. RP Dawes, AJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ronald Reagan UCLA Med Ctr, Dept Surg, 757 Westwood Plaza,Room B7-11, Los Angeles, CA 90095 USA. EM adawes@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 FU Veterans Affairs Robert Wood Johnson Clinical Scholars Program; Veterans Affairs Office of Academic Affiliations FX This study was supported by the Veterans Affairs Robert Wood Johnson Clinical Scholars Program (Drs Dawes and Sacks) and the Veterans Affairs Office of Academic Affiliations (Dr Dawes). NR 46 TC 8 Z9 8 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD OCT PY 2015 VL 150 IS 10 BP 965 EP 972 DI 10.1001/jamasurg.2015.1678 PG 8 WC Surgery SC Surgery GA DA1WB UT WOS:000367585200010 PM 26200744 ER PT J AU Robert, MC Choi, CJ Shapiro, FE Urman, RD Melki, S AF Robert, Marie-Claude Choi, Catherine J. Shapiro, Fred E. Urman, Richard D. Melki, Samir TI Avoidance of serious medical errors in refractive surgery using a custom preoperative checklist SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID INCORRECT SURGICAL-PROCEDURES; SAFETY CHECKLIST; OPERATING-ROOM; POPULATION; SYSTEM AB PURPOSE: To implement and measure the effect of a surgical safety checklist on the prevention of serious medical errors (never-events). SETTING: Boston Eye Group, Boston, Massachusetts, USA. DESIGN: Retrospective cohort study. METHODS: A safety checklist incorporating 28 sources of error was designed and implemented in December 2011 at the Boston Eye Group's refractive surgical center. Consecutive patients who had primary or enhancement laser vision correction (LVC) between July 2009 and February 2014 were included in this study. Before that date, a general checklist fashioned around the World Health Organization time-out procedure was used. The latter subjects were recruited as controls. The perioperative characteristics of both groups were retrospectively compared. RESULTS: The study comprised 2951 consecutive patients who had primary or enhancement LVC between July 2009 and February 2014; of these, 1417 patients (2744 eyes) had LVC after the implementation of a presurgical safety checklist. The general checklist fashioned around the World Health Organization time-out procedure was used for 1534 patients (2969 eyes). Both groups were comparable in patient age. The most common surgical procedures were laser in situ keratomileusis (78%) and laser-assisted subepithelial keratectomy with mitomycin-C (16%). Although there were 2 (0.07%) serious errors in the prechecklist cohort, none occurred following implementation of the safety checklist protocol (P = .23). The medical errors involved wrong refractive aim in 1 patient and wrong person wrong procedure wrong aim in another. CONCLUSIONS: Multiple potential sources of error exist in refractive surgery. The broad-scale implementation of a detailed presurgical safety checklist was helpful in minimizing and preventing serious errors (never-events) during LVC. (C) 2015 ASCRS and ESCRS C1 [Robert, Marie-Claude; Choi, Catherine J.; Melki, Samir] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Urman, Richard D.; Melki, Samir] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Shapiro, Fred E.; Melki, Samir] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Shapiro, Fred E.; Urman, Richard D.] Inst Safety Off Based Surg, Boston, MA USA. [Melki, Samir] Boston Eye Grp, Boston, MA USA. RP Melki, S (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM samir_melki@meei.harvard.edu NR 15 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 EI 1873-4502 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD OCT PY 2015 VL 41 IS 10 BP 2171 EP 2178 DI 10.1016/j.jcrs.2015.10.060 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DA0QW UT WOS:000367503200019 PM 26703293 ER PT J AU Streit, JJ Shishani, Y Greene, ME Nebergall, AK Wanner, JP Bragdgdon, CR Malchau, H Gobezie, R AF Streit, Jonathan J. Shishani, Yousef Greene, Meridith E. Nebergall, Audrey K. Wanner, John Paul Bragdgdon, Charles R. Malchau, Henrik Gobezie, Reuben TI Radiostereometric and Radiographic Analysis of Glenoid Component Motion After Total Shoulder Arthroplasty SO ORTHOPEDICS LA English DT Article ID CROSS-LINKED POLYETHYLENE; RANDOMIZED CONTROLLED-TRIAL; TOTAL HIP-ARTHROPLASTY; FOLLOW-UP; MICROMOVEMENT; COMPLICATIONS; REPLACEMENT; PROSTHESES; STABILITY; WEAR AB Aseptic glenoid component loosening is a common cause of total shoulder arthroplasty (TSA) failure, but early detection is difficult because pain often appears late and radiolucent lines are of uncertain significance. This study sought to answer the following questions: (1) What types of glenoid component motion may be observed during the first 3 years following implantation?; (2) Is the appearance of radiolucent lines around the glenoid component a reliable indicator of component motion?; and (3) Are clinical outcomes correlated with early glenoid component motion within the first 3 years after TSA? Eleven patients (mean age, 60.6 years) underwent TSA using a cemented, all-polyethylene glenoid component with tantalum bead implantation. Clinical outcomes (American Shoulder and Elbow Surgeons [ASES] score, visual analog scale [VAS] pain score, and range of motion) were compared pre- and postoperatively, and radiolucencies were graded according to the criteria of Lazarus et al. Patients were evaluated using radiostereometric analysis at 6 months and 1, 2, and 3 years postoperatively to measure component micromotion in translation and rotation. At a mean follow-up of 50.2 months, mean ASES score had improved from 30.3 to 81.3 (P<.001), mean VAS pain score had improved from 8 to 1 (P<.001), active forward flexion had improved from 109 degrees to 155 degrees (P=.001), active external rotation had improved from 28 degrees to 54 degrees (P=.003), and internal rotation had improved from the level of the sacrum to L3 (P=.002). Radiolucencies were detected around none of the components at 1 year, 6 components at 2 years, and 5 components at 3 years, and these radiolucencies were mostly found around components that experienced high levels of rotational motion. C1 [Streit, Jonathan J.] Case Western Reserve Univ, Dept Orthopaed Surg, Sch Med, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Shishani, Yousef; Wanner, John Paul; Gobezie, Reuben] Univ Hosp Cleveland, Cleveland Shoulder Inst, Mayfield Hts, OH USA. [Greene, Meridith E.; Nebergall, Audrey K.; Bragdgdon, Charles R.; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Gobezie, R (reprint author), Univ Hosp Cleveland, Cleveland Shoulder Inst, 3999 Richmond Rd,Ste 200, Beachwood, OH 44122 USA. EM reuben.gobezie@uhhospitals.org FU Biomet; Zimmer; Arthrex, Inc. FX Drs Streit, Shishani, and Bragdon and Mr Wanner have no relevant financial relationships to disclose. Dr Greene's institution receives grants from Biomet and Zimmer. Ms Nebergall's institution receives grants from Biomet and Zimmer. Dr Malchau is a board member of and holds stock in RSA Biomedical Co. Dr Gobezie is a paid consultant for and receives royalties from Arthrex, Inc. NR 26 TC 1 Z9 1 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 EI 1938-2367 J9 ORTHOPEDICS JI Orthopedics PD OCT PY 2015 VL 38 IS 10 BP E891 EP E897 DI 10.3928/01477447-20151002-56 PG 7 WC Orthopedics SC Orthopedics GA DA5IV UT WOS:000367837700007 PM 26488784 ER PT J AU Pitkanen, A Lukasiuk, K Dudek, FE Staley, KJ AF Pitkanen, Asla Lukasiuk, Katarzyna Dudek, F. Edward Staley, Kevin J. TI Epileptogenesis SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID TEMPORAL-LOBE EPILEPSY; TRAUMATIC BRAIN-INJURY; DENTATE GRANULE CELLS; SPONTANEOUS RECURRENT SEIZURES; CONTROLLED CORTICAL IMPACT; INDUCED STATUS EPILEPTICUS; FLUID PERCUSSION INJURY; MIDDLE CEREBRAL-ARTERY; SPRAGUE-DAWLEY RATS; TERM VIDEO-EEG AB Epileptogenesis is a chronic process that can be triggered by genetic or acquired factors, and that can continue long after epilepsy diagnosis. In 2015, epileptogenesis is not a treatment indication, and there are no therapies available in clinic to treat individuals at risk of epileptogenesis. However, thanks to active research, a large number of animal models have become available for search of molecular mechanisms of epileptogenesis. The first glimpses of treatment targets and biomarkers that could be developed to become useful in clinic are in sight. However, the heterogeneity of the epilepsy condition, and the dynamics of molecular changes over the course of epileptogenesis remain as challenges to overcome. C1 [Pitkanen, Asla] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Dept Neurobiol, FI-70211 Kuopio, Finland. [Pitkanen, Asla] Kuopio Univ Hosp, Dept Neurol, FI-70211 Kuopio, Finland. [Lukasiuk, Katarzyna] Polish Acad Sci, M Nencki Inst Expt Biol, PL-02093 Warsaw, Poland. [Dudek, F. Edward] Univ Utah, Dept Neurosurg, Sch Med, Salt Lake City, UT 84108 USA. [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Pitkanen, A (reprint author), Univ Eastern Finland, AI Virtanen Inst Mol Sci, Dept Neurobiol, FI-70211 Kuopio, Finland. EM asla.pitkanen@uef.fi RI Lukasiuk, Katarzyna/F-4636-2010 FU Academy of Finland; UEF Spearhead Project "UEF-Brain"; ERA-NET NEURON II [FA0200006175]; Polish National Research Centre Grant [2011/01/M/NZ3/02139]; Polish Ministry of Science and Education Grant [DNP/N119/ESF-EuroEPINOMICS/2012]; United States National Institutes of Health Grant [R01NS086364] FX This work is supported by the Academy of Finland (A.P.), UEF Spearhead Project "UEF-Brain" (A.P.), ERA-NET NEURON II FA0200006175 (A.P.), Polish National Research Centre Grant 2011/01/M/NZ3/02139 (K.L.), Polish Ministry of Science and Education Grant DNP/N119/ESF-EuroEPINOMICS/2012 (K.L.), and the United States National Institutes of Health Grant R01NS086364 (F.E.D. and K.J.S.). NR 126 TC 6 Z9 6 U1 2 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD OCT PY 2015 VL 5 IS 10 AR a022822 DI 10.1101/cshperspect.a022822 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CZ9WM UT WOS:000367448000009 ER PT J AU Vandenberghe, LH AF Vandenberghe, Luk H. TI What Is Next for Retinal Gene Therapy? SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID LEBERS CONGENITAL AMAUROSIS; RETINITIS-PIGMENTOSA; VIRAL VECTOR; DEGENERATION; TRANSDUCTION; EXPRESSION; VISION; SAFETY; MOUSE; VIVO AB The field of gene therapy for retinal blinding disorders is experiencing incredible momentum, justified by hopeful results in early stage clinical trials for inherited retinal degenerations. The premise of the use of the gene as a drug has come a long way, and may have found its niche in the treatment of retinal disease. Indeed, with only limited treatment options available for retinal indications, gene therapy has been proven feasible, safe, and effective and may lead to durable effects following a single injection. Here, we aim at putting into context the promise and potential, the technical, clinical, and economic boundaries limiting its application and development, and speculate on a future in which gene therapy is an integral component of ophthalmic clinical care. C1 [Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst,Med Sch, Ocular Genom Inst,Grousbeck Gene Therapy Ctr, Boston, MA 02114 USA. RP Vandenberghe, LH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst,Med Sch, Ocular Genom Inst,Grousbeck Gene Therapy Ctr, Boston, MA 02114 USA. EM luk_vandenberghe@meei.harvard.edu FU National Institutes of Health (NIH) [DP1-OD008267]; Curing Kids Fund; Foundation for Retina Research; Foundation Fighting Blindness; Research to Prevent Blindness; Grousbeck Family Foundation FX We thank Livia Carvalho, Heikki Turunen, and Eric Pierce for discussion and manuscript comments. Support for this work was from National Institutes of Health (NIH) Grant DP1-OD008267, Curing Kids Fund, Foundation for Retina Research, Foundation Fighting Blindness, Research to Prevent Blindness, and the Grousbeck Family Foundation. LHV is an inventor on patents related to AAV gene therapy; has served as a consultant and is inventor on technologies licensed to biotechnology and pharmaceutical industry; and is cofounder and consultant to GenSight Biologics. NR 39 TC 1 Z9 1 U1 3 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD OCT PY 2015 VL 5 IS 10 AR a017442 DI 10.1101/cshperspect.a017442 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CZ9WM UT WOS:000367448000002 ER PT J AU Cummings, S Pratt, J AF Cummings, Sue Pratt, Janey TI NUTRITION Metabolic and bariatric surgery Nutrition and dental considerations SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE Nutrition; bariatric surgery; obesity ID LAPAROSCOPIC SLEEVE GASTRECTOMY; CARDIOVASCULAR RISK-FACTORS; ASSOCIATION; OBESITY AB Background and Overview. Oral health care professionals may encounter patients who have had bariatric surgery and should be aware of the oral and nutritional implications of these surgeries. Bariatric surgery is an effective therapy for the treatment of obesity. Consistent with the 1991 National Institutes of Health Consensus Development Conference on Gastrointestinal Surgery for Severe Obesity recommendations, patients must meet body mass index (BMI) criteria for severe obesity, defined as a BMI greater than or equal to 40 kilograms per square meter, as well as for those with a BMI of greater than or equal to 35 kg/m(2) with significant comorbidities. Conclusions. Benefits of bariatric surgery in the treatment of severe obesity include significant and durable weight loss and improved or remission of obesity-related comorbidities including type 2 diabetes, hyperlipidemia, hypertension, heart disease, obstructive sleep apnea, and depression. Of the limited data published concerning the influences of bariatric surgical procedures on oral health, increased incidence of dental caries, periodontal diseases, and tooth wear have been reported in patients post-bariatric surgery. Practical Implications. The oral health care practitioner familiar with the most common bariatric procedures performed in the United States and their mechanisms of actions, risks, and benefits is in the position to provide guidance to patients on the nutritional and oral complications that can occur. C1 [Cummings, Sue] Massachusetts Gen Hosp, Clin Programs, Weight Ctr, Boston, MA 02114 USA. [Pratt, Janey] Massachusetts Gen Hosp, Surg, Weight Ctr, Boston, MA 02114 USA. RP Cummings, S (reprint author), Massachusetts Gen Hosp, Clin Programs, Weight Ctr, 50 Staniford St,4th Floor, Boston, MA 02114 USA. EM scummings1@partners.org NR 21 TC 0 Z9 0 U1 3 U2 7 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 2015 VL 146 IS 10 BP 767 EP 772 DI 10.1016/j.adaj.2015.06.004 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CZ8HK UT WOS:000367340600012 PM 26409987 ER PT J AU Obici, S Magrisso, IJ Ghazarian, AS Shirazian, A Miller, JR Loyd, CM Begg, DP Carhuatanta, KAK Haas, MK Davis, JF Woods, SC Sandoval, DA Seeley, RJ Goodyear, LJ Pothos, EN Mul, JD AF Obici, Silvana Magrisso, I. Jack Ghazarian, Armen S. Shirazian, Alireza Miller, Jonas R. Loyd, Christine M. Begg, Denovan P. Carhuatanta, Kimberly A. Krawczewski Haas, Michael K. Davis, Jon F. Woods, Stephen C. Sandoval, Darleen A. Seeley, Randy J. Goodyear, Laurie J. Pothos, Emmanuel N. Mul, Joram D. TI Moderate voluntary exercise attenuates the metabolic syndrome in melanocortin-4 receptor-deficient rats showing central dopaminergic dysregulation SO MOLECULAR METABOLISM LA English DT Article DE MC4R; Nucleus accumbens; Voluntary wheel running; Dopamine; Obesity; Diabetes; Food intake ID NUCLEUS-ACCUMBENS; SKELETAL-MUSCLE; DELTA-FOSB; ENERGY HOMEOSTASIS; DIETARY OBESITY; MESSENGER-RNA; FOOD-INTAKE; EXPRESSION; MICE; GENE AB Objective: Melanocortin-4 receptors (MC4Rs) are highly expressed by dopamine-secreting neurons of the mesolimbic tract, but their functional role has not been fully resolved. Voluntary wheel running (VWR) induces adaptations in the mesolimbic dopamine system and has a myriad of long-term beneficial effects on health. In the present experiments we asked whether MC4R function regulates the effects of VWR, and whether VWR ameliorates MC4R-associated symptoms of the metabolic syndrome. Methods: Electrically evoked dopamine release was measured in slice preparations from sedentary wild-type and MC4R-deficient Mc4r(K314X) (HOM) rats. VWR was assessed in wild-type and HOM rats, and in MC4R-deficient loxTB(Mc4r) mice, wild-type mice body weight-matched to loxTB(Mc4r) mice, and wild-type mice with intracerebroventricular administration of the MC4R antagonist SHU9119. Mesolimbic dopamine system function (gene/protein expression) and metabolic parameters were examined in wheel-running and sedentary wild-type and HOM rats. Results: Sedentary obese HOM rats had increased electrically evoked dopamine release in several ventral tegmental area (VTA) projection sites compared to wild-type controls. MC4R loss-of-function decreased VWR, and this was partially independent of body weight. HOM wheel-runners had attenuated markers of intracellular D1-type dopamine receptor signaling despite increased dopamine flux in the VTA. VWR increased and decreased Delta FosB D1-type levels in the nucleus accumbens (NAc) of wild-type and HOM runners, respectively. VWR improved metabolic parameters in wild-type wheel-runners. Finally, moderate voluntary exercise corrected many aspects of the metabolic syndrome in HOM runners. Conclusions: Central dopamine dysregulation during VWR reinforces the link between MC4R function and molecular and behavioral responding to rewards. The data also suggest that exercise can be a successful lifestyle intervention in MC4R-haploinsufficient individuals despite reduced positive reinforcement during exercise training. (C) 2015 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Obici, Silvana; Magrisso, I. Jack; Loyd, Christine M.; Begg, Denovan P.; Carhuatanta, Kimberly A. Krawczewski; Haas, Michael K.; Davis, Jon F.; Woods, Stephen C.; Mul, Joram D.] Univ Cincinnati, Metab Dis Inst, Cincinnati, OH USA. [Ghazarian, Armen S.; Shirazian, Alireza; Miller, Jonas R.; Pothos, Emmanuel N.] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Program Pharmacol & Expt Therapeut, Boston, MA 02111 USA. [Ghazarian, Armen S.; Shirazian, Alireza; Miller, Jonas R.; Pothos, Emmanuel N.] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Program Neurosci, Boston, MA 02111 USA. [Ghazarian, Armen S.; Shirazian, Alireza; Miller, Jonas R.; Pothos, Emmanuel N.] Tufts Univ, Sch Med, Dept Integrat Physiol & Pathobiol, Boston, MA 02111 USA. [Begg, Denovan P.] UNSW Australia, Sch Psychol, Sydney, NSW, Australia. [Sandoval, Darleen A.; Seeley, Randy J.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Goodyear, Laurie J.; Mul, Joram D.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Mul, JD (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. EM Joram.Mul@joslin.harvard.edu RI Begg, Denovan/A-7969-2012; OI Begg, Denovan/0000-0002-4551-2697; Pothos, Emmanuel/0000-0001-8825-7852 FU NIDDK NIH HHS [P30 DK020572] NR 79 TC 3 Z9 3 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2212-8778 J9 MOL METAB JI Mol. Metab. PD OCT PY 2015 VL 4 IS 10 BP 692 EP 705 DI 10.1016/j.molmet.2015.07.003 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CZ9WE UT WOS:000367447100004 PM 26500841 ER PT J AU Keuthen, NJ Tung, ES Altenburger, EM Blais, MA Pauls, DL Flessner, CA AF Keuthen, Nancy J. Tung, Esther S. Altenburger, Erin M. Blais, Mark A. Pauls, David L. Flessner, Christopher A. TI Trichotillomania and personality traits from the five-factor model SO REVISTA BRASILEIRA DE PSIQUIATRIA LA English DT Article DE Trichotillomania; personality; comorbidity ID OBSESSIVE-COMPULSIVE DISORDER; CLINICAL CHARACTERISTICS; HAIRPULLING SCALE AB Objective: To examine whether personality traits have predictive validity for trichotillomania (TTM) diagnosis, pulling severity and control, and hair pulling style. Methods: In study 1, logistic regression was used with TTM cases (n=54) and controls (n=25) to determine if NEO Five-Factor Inventory (NEO-FFI) personality domains predicted TTM case vs. control classification. In study 2, hierarchical multiple regression was used with TTM cases (n=164) to determine whether NEO-FFI personality domains predicted hair pulling severity and control as well as focused and automatic pulling styles. Results: TTM case vs. control status was predicted by NEO-FFI neuroticism. Every 1-point increase in neuroticism scores resulted in a 10% greater chance of TTM diagnosis. Higher neuroticism, higher openness, and lower agreeableness were associated with greater pulling severity. Higher neuroticism was also associated with less control over hair pulling. Higher neuroticism and lower openness were associated with greater focused pulling. None of the personality domains predicted automatic hair pulling. Conclusions: Personality traits, especially neuroticism, can predict TTM diagnosis, hair pulling severity and control, and the focused style of pulling. None of the personality traits predicted automatic pulling. Longitudinal studies are needed to determine whether personality variables predispose to TTM onset, impact disorder course, and/or result from hair pulling behavior. C1 [Keuthen, Nancy J.; Tung, Esther S.; Blais, Mark A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Altenburger, Erin M.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Pauls, David L.] Massachusetts Gen Hosp, Psychiat Neurogenet Unit, Boston, MA 02114 USA. [Flessner, Christopher A.] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. RP Keuthen, NJ (reprint author), Massachusetts Gen Hosp, Trichotillomania Clin, Simches Bldg,Fl-2,185 Cambridge St, Boston, MA 02114 USA. EM nkeuthen@partners.org RI Flessner, Christopher/K-1483-2015 FU Trichotillomania Learning Center, Inc. (TLC) and its BFRB Precision Medicine Initiative; Greater Kansas City Foundation FX We gratefully recognize financial support for this project from the Trichotillomania Learning Center, Inc. (TLC) and its BFRB Precision Medicine Initiative, as well as the Greater Kansas City Foundation. We also wish to express our gratitude to Lisa Osiecki who provided assistance with data management and to Amanda Falcon and Miriam Frank who performed data input and cleaning. NR 27 TC 1 Z9 1 U1 1 U2 6 PU ASSOC BRASILEIRA PSIQUIATRIA PI SAO PAULO PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO, SP 04039-032 A, BRAZIL SN 1516-4446 J9 REV BRAS PSIQUIATR JI Rev. Bras. Psiquiatr. PD OCT-DEC PY 2015 VL 37 IS 4 BP 317 EP 324 DI 10.1590/1516-4446-2015-1657 PG 8 WC Psychiatry SC Psychiatry GA CZ8IE UT WOS:000367342600008 PM 26375807 ER PT J AU Kubota, Y Hasegawa, K Taguchi, H Kitamura, T Nishiyama, C Iwami, T Nishiuchi, T Hiraide, A AF Kubota, Yoshie Hasegawa, Kohei Taguchi, Hirokazu Kitamura, Tetsuhisa Nishiyama, Chika Iwami, Taku Nishiuchi, Tatsuya Hiraide, Atsushi TI Characteristics and trends of emergency patients with drug overdose in Osaka SO ACUTE MEDICINE & SURGERY LA English DT Article DE Ambulance diversion; drug overdose; emergency medical services; hospital arrival time; transportation of patients ID DEPARTMENT VISITS; OUTCOMES; PATTERNS; HEROIN; UK AB AimDrug overdose is an important issue in emergency medicine. However, studies covering overdose patients transported by ambulance have not been sufficiently carried out. We attempted to clarify problems of suspected drug overdose patients transported by ambulance. MethodsThis is a prospective population-based cohort study. Data were collected by emergency medical service crews in Osaka City, Japan, between January 1998 and December 2010. ResultsDrug overdose cases increased annually from 1,136 in 1998 to 1,822 in 2010 (P<0.0001 for trend). In these cases, the dominant age range was between 16 and 40 years and the age distribution did not change over time. The age of non-overdose cases increased (P<0.0001 for trend), with patients aged 66 years becoming most common in recent years, reflecting the aging of society. Males comprised most non-overdose patients, but the percentage of females increased annually (P<0.0001 in trend). Females comprised approximately 70% in overdose cases annually throughout the study period. The duration from the emergency call to the arrival at the hospital for overdose patients has increased markedly in recent years. It also takes more time to obtain acceptance from hospitals to care for patients of suspected overdose. ConclusionThe characteristics of drug overdose patients are clearly different from those of non-overdose patients. Recent trends of drug overdose patients indicate the accelerated burden on emergency medical services system. C1 [Kubota, Yoshie; Taguchi, Hirokazu; Nishiuchi, Tatsuya; Hiraide, Atsushi] Kinki Univ, Fac Med, Dept Acute Med, Osakasayama, Osaka 5898511, Japan. [Hasegawa, Kohei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Kitamura, Tetsuhisa] Osaka Univ, Grad Sch Med, Dept Social & Environm Med, Div Environm Med & Populat Sci, Osaka, Japan. [Nishiyama, Chika] Grad Sch Med, Sch Human Hlth Sci, Dept Crit Care Nursing, Kyoto, Japan. [Iwami, Taku] Kyoto Univ, Hlth Serv, Kyoto, Japan. RP Hiraide, A (reprint author), Kinki Univ, Fac Med, Dept Acute Med, 377-2 Ohno Higashi, Osakasayama, Osaka 5898511, Japan. EM hiraide@med.kindai.ac.jp NR 26 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2052-8817 J9 ACUTE MED SURG JI Acute Med. Surg. PD OCT PY 2015 VL 2 IS 4 BP 237 EP 243 DI 10.1002/ams2.107 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CU3TH UT WOS:000363447700003 ER PT J AU Castillo, J Glezerman, I Boklage, S Lamerato, L Chiodo, J Tidwell, B Schulman, K AF Castillo, Jorge Glezerman, Ilya Boklage, Susan Lamerato, Lois Chiodo, Joseph Tidwell, Beni Schulman, Kathy TI Incidence and Prognostic Importance of Hyponatremia in a Cohort of Patients With Lung Cancers SO CHEST LA English DT Meeting Abstract C1 [Castillo, Jorge; Glezerman, Ilya; Boklage, Susan; Lamerato, Lois; Chiodo, Joseph; Tidwell, Beni; Schulman, Kathy] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 SU S MA 552A DI 10.1378/chest.2268164 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CZ5SU UT WOS:000367163100007 ER PT J AU Channick, R Chin, K Di Scala, L Frey, A Preiss, R Gaine, S Galie, N Ghofrani, HA Hoeper, M Lang, I McLaughlin, V Rubin, L Simonneau, G Sitbon, O Tapson, V AF Channick, Richard Chin, Kelly Di Scala, Lilla Frey, Aline Preiss, Ralph Gaine, Sean Galie, Nazzareno Ghofrani, Hossein Ardeschir Hoeper, Marius Lang, Irene McLaughlin, Vallerie Rubin, Lewis Simonneau, Gerald Sitbon, Olivier Tapson, Victor TI Individualized Dosing of Selexipag Based on Tolerability in the GRIPHON Study Shows Consistent Efficacy and Safety in Patients With Pulmonary Arterial Hypertension (PAH) SO CHEST LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Actel Pharmaceut Ltd, Allschwil, Switzerland. Mater Misericordiae Univ Hosp, Natl Pulm Hypertens Unit, Dublin, Ireland. Univ Bologna, Ist Malattie Apparato Cardiovasc, Bologna, Italy. Univ Giessen, D-35390 Giessen, Germany. Marburg Lung Ctr, Giessen, Germany. Hannover Med Sch, Dept Resp Med, Hannover, Germany. German Ctr Lung Res, Hannover, Germany. Med Univ Vienna, Dept Internal Med 2, Div Cardiol, Allgemeines Krankenhaus, Vienna, Austria. Univ Michigan Hlth Syst, Div Cardiovasc Med, Ann Arbor, MI USA. Univ Calif San Diego, Div Pulm & Crit Care Med, San Diego, CA 92103 USA. Univ Paris 11, Hop Univ Bicetre, Paris, France. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 SU S MA 961A DI 10.1378/chest.2256760 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CZ5SU UT WOS:000367163100411 ER PT J AU Clark, M Cummings, B Kuhlthau, K Frassica, N Noviski, N AF Clark, Maureen Cummings, Brian Kuhlthau, Karen Frassica, Natalie Noviski, Natan TI Nonmedical Out-of-Pocket Expenses, Work Absenteeism, and Productivity for Families With a Child Admitted to the Pediatric Intensive Care Unit SO CHEST LA English DT Meeting Abstract C1 [Clark, Maureen; Cummings, Brian; Kuhlthau, Karen; Frassica, Natalie; Noviski, Natan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 SU S MA 223A DI 10.1378/chest.2220469 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CY0ZB UT WOS:000366134400217 ER PT J AU Godbole, R Zider, A Betancourt, J Saggar, R Kamangar, N AF Godbole, Rohit Zider, Alexander Betancourt, Jaime Saggar, Rajan Kamangar, Nader TI Achieving Early Diagnosis of Pulmonary Tumor Thrombotic Microangiopathy: A Case Series SO CHEST LA English DT Meeting Abstract C1 [Godbole, Rohit; Zider, Alexander; Betancourt, Jaime; Saggar, Rajan; Kamangar, Nader] VA Greater Los Angeles Healthcare Syst GLA, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 SU S MA 1003A DI 10.1378/chest.2276141 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CZ5SU UT WOS:000367163100453 ER PT J AU Hoo, GS Barack, B Vazirani, S Li, ZP Wu, C AF Hoo, Guy Soo Barack, Bruce Vazirani, Sondra Li, Zhaoping Wu, Carol TI The Increasing Use of D-Dimer Testing in Suspected Pulmonary Embolism SO CHEST LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 SU S MA 918A DI 10.1378/chest.2281445 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CZ5SU UT WOS:000367163100368 ER PT J AU Landry, AM AF Landry, Alden M. TI BLACK MAN IN A WHITE COAT: A DOCTOR'S REFLECTIONS ON RACE AND MEDICINE SO HEALTH AFFAIRS LA English DT Book Review C1 [Landry, Alden M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Landry, Alden M.] Tour Divers Med, Columbia, SC USA. [Landry, Alden M.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Landry, Alden M.] Harvard Univ, Med Sch, Off Divers Inclus & Community Partnership, Cambridge, MA 02138 USA. RP Landry, AM (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM alden@tour4diversity.org NR 1 TC 0 Z9 0 U1 3 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD OCT PY 2015 VL 34 IS 10 BP 1795 EP 1795 DI 10.1377/hlthaff.2015.1056 PG 1 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CY9JR UT WOS:000366723700031 ER PT J AU Lee, SH Byrne, EM Hultman, CM Kahler, A Vinkhuyzen, AAE Ripke, S Andreassen, OA Frisell, T Gusev, A Hu, XL Karlsson, R Mantzioris, VX McGrath, JJ Mehta, D Stahl, EA Zhao, QY Kendler, KS Sullivan, PF Price, AL O'Donovan, M Okada, Y Mowry, BJ Raychaudhuri, S Wray, NR AF Lee, S. Hong Byrne, Enda M. Hultman, Christina M. Kahler, Anna Vinkhuyzen, Anna A. E. Ripke, Stephan Andreassen, Ole A. Frisell, Thomas Gusev, Alexander Hu, Xinli Karlsson, Robert Mantzioris, Vasilis X. McGrath, John J. Mehta, Divya Stahl, Eli A. Zhao, Qiongyi Kendler, Kenneth S. Sullivan, Patrick F. Price, Alkes L. O'Donovan, Michael Okada, Yukinori Mowry, Bryan J. Raychaudhuri, Soumya Wray, Naomi R. CA Schizophrenia Working Grp Psychiat TI New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Schizophrenia; rheumatoid arthritis; genetic relationship; pleiotropy ID GENOME-WIDE ASSOCIATION; AUTOIMMUNE-DISEASES; RISK LOCI; VITAMIN-D; BIPOLAR DISORDER; COMMON VARIANTS; ANTIBODY STATUS; FAMILIAL RISKS; IMMUNE-SYSTEM; SUSCEPTIBILITY AB Background: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders. Methods: We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born. Results: We estimate a small but significant negative SNP-genetic correlation between SZ and RA (-0.046, s.e. 0.026,P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (-0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14,P = 0.00090). Conclusions: Our results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context. C1 [Lee, S. Hong; Byrne, Enda M.; Vinkhuyzen, Anna A. E.; Mantzioris, Vasilis X.; McGrath, John J.; Mehta, Divya; Zhao, Qiongyi; Mowry, Bryan J.; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Lee, S. Hong] Univ New England, Sch Environm & Rural Sci, Armidale, NSW, Australia. [Hultman, Christina M.; Kahler, Anna; Karlsson, Robert] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ripke, Stephan] Harvard Univ, Sch Med, Boston, MA USA. [Ripke, Stephan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Ripke, Stephan] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany. [Andreassen, Ole A.] Univ Oslo, NORMENT KG Jebsen Ctr Psychosis Res, Inst Clin Med, Oslo, Norway. [Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway. [Frisell, Thomas] Karolinska Inst, Clin Epidemiol Unit, Stockholm, Sweden. [Gusev, Alexander; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gusev, Alexander; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Gusev, Alexander; Price, Alkes L.] Broad Inst, Med & Populat Genet Program, Cambridge, MA USA. [Hu, Xinli] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Hu, Xinli] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Hu, Xinli] Broad Inst, Med & Populat Genet Grp, Cambridge, MA USA. [Hu, Xinli] Harvard Univ, Hlth Sci & Technol MD Program, Boston, MA 02115 USA. [Hu, Xinli] MIT, Boston, MA 02115 USA. [McGrath, John J.] Pk Ctr Mental Hlth, Queensland Ctr Mental Hlth Res, Richlands, Qld, Australia. [Stahl, Eli A.] Mt Sinai Sch Med, Div Psychiat Genom, New York, NY USA. [Kendler, Kenneth S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA. [Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [O'Donovan, Michael] Cardiff Univ, Sch Med, Ctr Neuropsychiat Genet & Gen, MRC, Cardiff CF10 3AX, S Glam, Wales. [O'Donovan, Michael] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales. [Okada, Yukinori; Raychaudhuri, Soumya] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Okada, Yukinori; Raychaudhuri, Soumya] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Okada, Yukinori; Raychaudhuri, Soumya] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Okada, Yukinori] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Div, Tokyo, Japan. [Mowry, Bryan J.] Queensland Ctr Mental Hlth Res, Wacol, Qld, Australia. [Raychaudhuri, Soumya] Partners Ctr Personalized Genet Med, Boston, MA USA. [Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester, Lancs, England. RP Wray, NR (reprint author), Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. EM naomi.wray@uq.edu.au RI Hansen, Thomas Folkmann/O-5965-2014; Stroup, Thomas/F-9188-2014; Siminovitch, Katherine/K-1475-2013; Melle, Ingrid /B-4858-2011; Ruderfer, Douglas/M-5795-2016; Lee, Sang Hong/A-2569-2011; McQuillin, Andrew/C-1623-2008; Frisell, Thomas/E-2772-2017; OI Myin-Germeys, Inez/0000-0002-3731-4930; Gill, Michael/0000-0003-0206-5337; Escott-Price, Valentina/0000-0003-1784-5483; Hansen, Thomas Folkmann/0000-0001-6703-7762; Frisell, Thomas/0000-0002-5735-9626; Bruggeman, Richard/0000-0002-3238-8471; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Vinkhuyzen, Anna/0000-0003-3352-0603; Visscher, Peter/0000-0002-2143-8760; Zammit, Stanley/0000-0002-2647-9211; Stroup, Thomas/0000-0002-3123-0672; Melle, Ingrid /0000-0002-9783-548X; Ruderfer, Douglas/0000-0002-2365-386X; Lee, Sang Hong/0000-0001-9701-2718; McQuillin, Andrew/0000-0003-1567-2240; Mattheisen, Manuel/0000-0002-8442-493X; Corvin, Aiden/0000-0001-6717-4089; Agartz, Ingrid/0000-0002-9839-5391; Karlsson, Robert/0000-0002-8949-2587; Padyukov, Leonid/0000-0003-2950-5670; McIntosh, Andrew/0000-0002-0198-4588 FU Australian Research Council [DE130100614]; National Health and Medical Research Council [613602, 1078901, 1047956, 1053639]; Arthritis Foundation; Doris Duke Foundation; National Institutes of Health [1R01AR063759-01A1, 1U01HG0070033, 5U01GM092691-04, R01 MH077139]; Karolinska Institutet; Karolinska University Hospital; Swedish Research Council; Netherlands Scientific Organization [NWO 480-05-003]; Dutch Brain Foundation; VU University Amsterdam; Vanderbilt CTSA from NCATS/NIH [ULTR000445] FX This work was supported by the Australian Research Council [grant number DE130100614 to S.H.L.], the National Health and Medical Research Council [grant numbers 613602, 1078901 to N.R.W; 1047956 to N.R.W., S.H.L. and B.J.M., 1053639 to E.M.B]; the Arthritis Foundation to S.R., the Doris Duke Foundation to S.R.; the National Institutes of Health [grant numbers 1R01AR063759-01A1, 1U01HG0070033, 5U01GM092691-04 to S.R.; R01 MH077139 for the Sweden SZ Study to P.F.S.]. The Swedish SZ study was also funded by the Karolinska Institutet, Karolinska University Hospital, and the Swedish Research Council. The RA dataset from Vanderbilt University Medical Center's BioVU is supported by institutional funding and by the Vanderbilt CTSA grant ULTR000445 from NCATS/NIH. Other funding acknowledgements can be found in the primary publications from each study, as references. Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara, and financially supported by The Netherlands Scientific Organization (NWO 480-05-003) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. NR 71 TC 7 Z9 7 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 2015 VL 44 IS 5 BP 1706 EP 1721 DI 10.1093/ije/dyv136 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CZ5YJ UT WOS:000367178000038 PM 26286434 ER PT J AU Yeo, BTT Krienen, FM Eickhoff, SB Yaakub, SN Fox, PT Buckner, RL Asplund, CL Chee, MWL AF Yeo, B. T. Thomas Krienen, Fenna M. Eickhoff, Simon B. Yaakub, Siti N. Fox, Peter T. Buckner, Randy L. Asplund, Christopher L. Chee, Michael W. L. TI Functional Specialization and Flexibility in Human Association Cortex SO CEREBRAL CORTEX LA English DT Article DE cognitive ontology; functional connectivity; meta-analysis; parietal cortex; prefrontal cortex ID HUMAN CEREBRAL-CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; ACTIVATION-BASED PARCELLATION; INFERIOR PREFRONTAL CORTEX; NEUROIMAGING DATA; HUMAN-BRAIN; COGNITIVE CONTROL; PARIETAL CORTEX; CONNECTIVITY NETWORKS; CORTICAL CONNECTIONS AB The association cortex supports cognitive functions enabling flexible behavior. Here, we explored the organization of human association cortex by mathematically formalizing the notion that a behavioral task engages multiple cognitive components, which are in turn supported by multiple overlapping brain regions. Application of the model to a large data set of neuroimaging experiments (N = 10 449) identified complex zones of frontal and parietal regions that ranged from being highly specialized to highly flexible. The network organization of the specialized and flexible regions was explored with an independent resting-state fMRI data set (N = 1000). Cortical regions specialized for the same components were strongly coupled, suggesting that components function as partially isolated networks. Functionally flexible regions participated in multiple components to different degrees. This heterogeneous selectivity was predicted by the connectivity between flexible and specialized regions. Functionally flexible regions might support binding or integrating specialized brain networks that, in turn, contribute to the ability to execute multiple and varied tasks. C1 [Yeo, B. T. Thomas] Natl Univ Singapore, Dept Elect & Comp Engn, Singapore 117583, Singapore. [Yeo, B. T. Thomas; Asplund, Christopher L.] Natl Univ Singapore, Singapore Inst Neurotechnol, Singapore 117583, Singapore. [Yeo, B. T. Thomas] Natl Univ Singapore, Clin Imaging Res Ctr, Singapore 117583, Singapore. [Yeo, B. T. Thomas; Yaakub, Siti N.; Asplund, Christopher L.; Chee, Michael W. L.] Duke NUS Grad Med Sch, Ctr Cognit Neurosci, Singapore, Singapore. [Yeo, B. T. Thomas; Krienen, Fenna M.; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Krienen, Fenna M.; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Krienen, Fenna M.; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. [Eickhoff, Simon B.] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Pokfulam, Hong Kong, Peoples R China. [Asplund, Christopher L.] Yale NUS Coll, Div Social Sci, Singapore, Singapore. RP Yeo, BTT (reprint author), Natl Univ Singapore, Dept Elect & Comp Engn, Block E4 Level 5 Room 45,4 Engn Dr 3, Singapore 117583, Singapore. EM thomas.yeo@nus.edu.sg OI Yeo, B.T. Thomas/0000-0002-0119-3276; Chee, Michael/0000-0002-6087-0548 FU Singapore NMRC [STaR/0004/2008, CBRG14nov007]; Singapore MOE Tier 2 [MOE2014-T2-2-016]; NUS Strategic Research [DPRT/944/09/14]; NUS SOM Aspiration Fund [R185000271720]; MGH-UCLA Human Connectome Project [U54MH091665]; Simons Foundation; Howard Hughes Medical Institute; NUS Tier 1 FX This work was supported by Singapore NMRC STaR/0004/2008, NUS Tier 1, Singapore MOE Tier 2 (MOE2014-T2-2-016), NUS Strategic Research (DPRT/944/09/14), NUS SOM Aspiration Fund (R185000271720), Singapore NMRC CBRG14nov007, MGH-UCLA Human Connectome Project (U54MH091665), the Simons Foundation, and the Howard Hughes Medical Institute. NR 102 TC 23 Z9 24 U1 3 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD OCT PY 2015 VL 25 IS 10 BP 3654 EP 3672 DI 10.1093/cercor/bhu217 PG 19 WC Neurosciences SC Neurosciences & Neurology GA CY5NI UT WOS:000366454000032 PM 25249407 ER PT J AU Jensen, KB Kaptchuk, TJ Chen, XY Kirsch, I Ingvar, M Gollub, RL Kong, J AF Jensen, Karin B. Kaptchuk, Ted J. Chen, Xiaoyan Kirsch, Irving Ingvar, Martin Gollub, Randy L. Kong, Jian TI A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses SO CEREBRAL CORTEX LA English DT Article DE amygdala; conditioning; nocebo effect; placebo effect; subliminal perception ID HUMAN ORBITOFRONTAL CORTEX; INDUCED EXPECTATIONS; HUMAN AMYGDALA; FEAR-RELEVANT; ANALGESIA; REWARD; PAIN; NETWORK; BRAIN; STIMULI AB Fundamental aspects of human behavior operate outside of conscious awareness. Yet, theories of conditioned responses in humans, such as placebo and nocebo effects on pain, have a strong emphasis on conscious recognition of contextual cues that trigger the response. Here, we investigated the neural pathways involved in nonconscious activation of conditioned pain responses, using functional magnetic resonance imaging in healthy participants. Nonconscious compared with conscious activation of conditioned placebo analgesia was associated with increased activation of the orbitofrontal cortex, a structure with direct connections to affective brain regions and basic reward processing. During nonconscious nocebo, there was increased activation of the thalamus, amygdala, and hippocampus. In contrast to previous assumptions about conditioning in humans, our results show that conditioned pain responses can be elicited independently of conscious awareness and our results suggest a hierarchical activation of neural pathways for nonconscious and conscious conditioned responses. Demonstrating that the human brain has a nonconscious mechanism for responding to conditioned cues has major implications for the role of associative learning in behavioral medicine and psychiatry. Our results may also open up for novel approaches to translational animal-to-human research since human consciousness and animal cognition is an inherent paradox in all behavioral science. C1 [Jensen, Karin B.; Chen, Xiaoyan; Gollub, Randy L.; Kong, Jian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. [Jensen, Karin B.; Kaptchuk, Ted J.; Kirsch, Irving; Gollub, Randy L.; Kong, Jian] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA. [Kirsch, Irving] Univ Plymouth, Sch Psychol, Plymouth PL4 8AA, Devon, England. [Ingvar, Martin] Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden. RP Jensen, KB (reprint author), Karolinska Inst, Dept Clin Neurosci, Retzuis Vag 8, S-17176 Stockholm, Sweden. EM karinj@nmr.mgh.harvard.edu OI Jensen, Karin/0000-0003-2521-3160; Ingvar, Martin/0000-0002-9041-5714 FU COFAS Marie Curie Postdoc Program and Osher Center for Integrative Medicine at Karolinska Institutet [R01AT006364, R21AT004497, R03AT218317, K24 AT004095, R01AT005280, UL1 RR025758-01, P41RR14075]; Karolinska Institute FX This work was supported by the COFAS Marie Curie Postdoc Program and Osher Center for Integrative Medicine at Karolinska Institutet to K.J.; R01AT006364 (NCCAM), R21AT004497 (NCCAM), R03AT218317 (NIDA) to J.K.; K24 AT004095 (NCCAM) to T.K.; R01AT005280 (NCCAM) to R.G.; UL1 RR025758-01 (NCRR) P41RR14075 (NCRR) to Bruce Rosen. Funding to pay the Open Access publication charges for this article was provided by the Karolinska Institute. NR 51 TC 5 Z9 5 U1 2 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD OCT PY 2015 VL 25 IS 10 BP 3903 EP 3910 DI 10.1093/cercor/bhu275 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CY5NI UT WOS:000366454000050 PM 25452576 ER PT J AU Nasr, S Stemmann, H Vanduffel, W Tootell, RBH AF Nasr, Shahin Stemmann, Heiko Vanduffel, Wim Tootell, Roger B. H. TI Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex SO CEREBRAL CORTEX LA English DT Article DE DMN; fMRI; homology; size response function; temporal cortex ID TEMPORO-PARIETAL JUNCTION; BIOLOGICAL MOTION PERCEPTION; BRAINS DEFAULT NETWORK; STIMULUS-INDEPENDENT THOUGHT; MEDIAL PREFRONTAL CORTEX; FACE PROCESSING NETWORK; HUMAN CEREBRAL-CORTEX; MIRROR NEURON SYSTEM; MORAL JUDGMENT; MODE NETWORK AB Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this "reversed" size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys. C1 [Nasr, Shahin; Vanduffel, Wim; Tootell, Roger B. H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Nasr, Shahin; Vanduffel, Wim; Tootell, Roger B. H.] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. [Stemmann, Heiko; Vanduffel, Wim] Katholieke Univ Leuven, Sch Med, Lab Neuro & Psychophysiol, B-3000 Leuven, Belgium. RP Nasr, S (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM shahin@nmr.mgh.harvard.edu FU National Institutes of Health (NIH) [R01 MH67529, R01 EY017081]; FWO-Vlaanderen (FWO) [G0A5613N, G043912N]; Martinos Center for Biomedical Imaging; NCRR; MIND Institute; NIMH Intramural Research Program; PF; [IUAP7-11] FX This study was supported by National Institutes of Health (NIH Grants R01 MH67529 and R01 EY017081) to RBHT, FWO-Vlaanderen (FWO Grants G0A5613N and G043912N) and IUAP7-11 and PF to WV, the Martinos Center for Biomedical Imaging, the NCRR, the MIND Institute, and the NIMH Intramural Research Program. Funding to pay the Open Access publication charges for this article was provided by NIH Grants R01 EY017081 to RBHT. NR 155 TC 4 Z9 4 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD OCT PY 2015 VL 25 IS 10 BP 4009 EP 4028 DI 10.1093/cercor/bhu290 PG 20 WC Neurosciences SC Neurosciences & Neurology GA CY5NI UT WOS:000366454000057 PM 25480358 ER PT J AU Dalvie, S Koen, N Duncan, L Abbo, C Akena, D Atwoli, L Chiliza, B Donald, KA Kinyanda, E Lochner, C Mall, S Nakasujja, N Newton, CR Ramesar, R Sibeko, G Teferra, S Stein, DJ Koenen, KC AF Dalvie, Shareefa Koen, Nastassja Duncan, Laramie Abbo, Catherine Akena, Dickens Atwoli, Lukoye Chiliza, Bonginkosi Donald, Kirsten A. Kinyanda, Eugene Lochner, Christine Mall, Sumaya Nakasujja, Noeline Newton, Charles R. Ramesar, Raj Sibeko, Goodman Teferra, Solomon Stein, Dan J. Koenen, Karestan C. TI Large Scale Genetic Research on Neuropsychiatric Disorders in African Populations is Needed SO EBIOMEDICINE LA English DT Editorial Material DE Psychiatry; Genetics; Africa; Neuropsychiatry ID GENOME-WIDE ASSOCIATION C1 [Dalvie, Shareefa; Ramesar, Raj] Univ Cape Town, Inst Infect Dis & Mol Med, Div Human Genet, MRC UCT Human Genet Res Unit, ZA-7925 Cape Town, South Africa. [Dalvie, Shareefa; Koen, Nastassja; Mall, Sumaya; Sibeko, Goodman; Stein, Dan J.] Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa. [Koen, Nastassja; Lochner, Christine; Stein, Dan J.] Med Res Council MRC Unit Anxiety & Stress Disorde, Cape Town, South Africa. [Duncan, Laramie] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Duncan, Laramie; Koenen, Karestan C.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA. [Duncan, Laramie] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Duncan, Laramie] Harvard Univ, Sch Med, Boston, MA USA. [Abbo, Catherine; Akena, Dickens; Kinyanda, Eugene; Nakasujja, Noeline] Makerere Univ, Coll Hlth Sci, Sch Med, Dept Psychiat, Kampala, Uganda. [Atwoli, Lukoye] Moi Univ, Coll Hlth Sci, Sch Med, Dept Mental Hlth, Eldoret, Kenya. [Chiliza, Bonginkosi; Lochner, Christine] Univ Stellenbosch, Fac Med & Hlth Sci, Dept Psychiat, Cape Town, Western Cape, South Africa. [Donald, Kirsten A.] Univ Cape Town, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, ZA-7925 Cape Town, South Africa. [Kinyanda, Eugene] MRC UVRI Uganda Res Unit AIDS, Entebbe, Uganda. [Newton, Charles R.] KEMRI Wellcome Trust Res Programme, Kilifi, Kenya. [Newton, Charles R.] Univ Oxford, Dept Psychiat, Oxford, England. [Teferra, Solomon] Univ Addis Ababa, Coll Hlth Sci, Sch Med, Dept Psychiat, Addis Ababa, Ethiopia. [Koenen, Karestan C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Koenen, Karestan C.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Koenen, Karestan C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Dalvie, S (reprint author), Univ Cape Town, Inst Infect Dis & Mol Med, Div Human Genet, MRC UCT Human Genet Res Unit, ZA-7925 Cape Town, South Africa. EM dlvsha006@myuct.ac.za RI Stein, Dan/A-1752-2008; Donald, Kirsty/H-9328-2015; OI Stein, Dan/0000-0001-7218-7810; Abbo, Catherine/0000-0002-5972-6194; Atwoli, Lukoye/0000-0001-7710-9723 FU Medical Research Council [MR/L004623/1]; Wellcome Trust [092654] NR 9 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD OCT PY 2015 VL 2 IS 10 BP 1259 EP 1261 DI 10.1016/j.ebiom.2015.10.002 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CX8ND UT WOS:000365959700002 PM 26629498 ER PT J AU Xia, W Chiu, YH Williams, PL Gaskins, AJ Toth, TL Tanrikut, C Hauser, R Chavarro, JE AF Xia, Wei Chiu, Yu-Han Williams, Paige L. Gaskins, Audrey J. Toth, Thomas L. Tanrikut, Cigdem Hauser, Russ Chavarro, Jorge E. TI Men's meat intake and treatment outcomes among couples undergoing assisted reproduction SO FERTILITY AND STERILITY LA English DT Article DE Cohort studies; men; meat intake; infertility; assisted reproductive technology ID FOOD FREQUENCY QUESTIONNAIRE; YOUNG DANISH MEN; BODY-MASS INDEX; SEMEN QUALITY; INFERTILITY; POPULATION; PARAMETERS; PREGNANCY; FERTILITY; REPRODUCIBILITY AB Objective: To study the relationship between men's meat intake and clinical outcomes in couples undergoing infertility treatment with the use of assisted reproductive technology (ART). Design: Prospective cohort study. Setting: Fertility center. Patient(s): A total of 141 men whose female partners underwent 246 ART cycles from 2007 to 2014. Intervention(s): None. Total and specific types of meat intake were estimated from dietary questionnaires. Main Outcome Measure(s): Fertilization, implantation, clinical pregnancy, and live-birth rates per initiated cycle. Mixed-effects models account for multiple IVF cycles per woman. Result(s): There was a positive association between poultry intake and fertilization rate, with a 13% higher fertilization rate among men in the highest quartile of poultry intake compared with those in the lowest quartile (78% vs. 65%). Processed meat intake was inversely related to fertilization rate in conventional IVF cycles but not in IVF cycles using intracytoplasmic sperm injection. The adjusted fertilization rates for men in increasing quartiles of processed meat intake were 82%, 67%, 70%, and 54% in conventional IVF cycles. Men's total meat intake, including intake of specific types of meat, was not associated with implantation, clinical pregnancy, or live-birth rates. Conclusion(s): Poultry intake was positively associated with fertilization rates, whereas processed meat intake was negatively associated with fertilization rates among couples undergoing conventional IVF. This, however, did not translate into associations with clinical pregnancy or live-birth rates. (C)2015 by American Society for Reproductive Medicine. C1 [Xia, Wei; Chiu, Yu-Han; Gaskins, Audrey J.; Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Williams, Paige L.; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Toth, Thomas L.; Hauser, Russ] Massachusetts Gen Hosp, Dept Gynecol, Boston, MA 02114 USA. [Tanrikut, Cigdem] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Xia, Wei] Huazhong Univ Sci & Technol, Family Planning Res, Wuhan, Hubei, Peoples R China. [Xia, Wei] Huazhong Univ Sci & Technol, Reprod Med Ctr, Wuhan, Hubei, Peoples R China. RP Chavarro, JE (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM jchavarr@hsph.harvard.edu FU National Institutes of Health [R01ES009718, R01ES022955, P30ES000002, P30DK46200, T32DK007703]; China Scholarship Council FX Supported by National Institutes of Health grant nos. R01ES009718, R01ES022955, P30ES000002, P30DK46200, and T32DK007703. W.X. was supported by the China Scholarship Council. NR 25 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2015 VL 104 IS 4 BP 972 EP 979 DI 10.1016/j.fertnstert.2015.06.037 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CY5ZD UT WOS:000366485700028 PM 26206344 ER PT J AU Abati, S Villa, A Cetin, I AF Abati, Silvio Villa, Alessandro Cetin, Irene TI Oral environment, inflammation and preterm birth SO JOURNAL OF PEDIATRIC AND NEONATAL INDIVIDUALIZED MEDICINE LA English DT Review DE Periodontal diseases; oral diseases; inflammation; gingivitis; periodontitis; mucositis ID ADVERSE PREGNANCY OUTCOMES; PERIODONTAL-DISEASE; MATERNAL PERIODONTITIS; ASSOCIATION; INFECTION; WEIGHT; RISK; DELIVERY; MOTHERS AB Adverse obstetric outcomes are determinants of neonatal mortality and serious morbidity, often leading to neurologic and developmental alterations in early childhood and/or adult life. Several studies have focused the relationships between maternal inflammation and diseases and those conditions. The role of oral inflammation and gingival diseases as factors with potential maternal and fetal detrimental effects on the outcomes of pregnancy is a relatively new area of investigation that has attracted a lot of interest and research in the last twenty years. The new evidences now strongly support a role for maternal infection and inflammation of the genital tract, as well as inflammation from sites distant from the pelvis, in the etiology of preterm birth. The aim of the present paper is to outline and summarize the current knowledge about the relations between oral biofilms, periodontal inflammation and the pathogenic mechanisms linking periodontal diseases with adverse pregnancy outcomes, concluding with some practical advices for clinicians on the prevention and control of the oral inflammation and the related adverse outcomes in pregnant patients. C1 [Abati, Silvio] Univ Milan, Dent Clin, San Paolo Hosp, Sch Med & Dent, I-20142 Milan, Italy. [Villa, Alessandro] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Oral Med & Dent, Boston, MA 02115 USA. [Cetin, Irene] Univ Milan, L Sacco Hosp, Sch Med, Obstet & Gynecol, I-20142 Milan, Italy. RP Abati, S (reprint author), Univ Milan, Dent Clin, Via Beldiletto 1, I-20142 Milan, Italy. EM silvio.abati@unimi.it NR 35 TC 0 Z9 0 U1 1 U2 4 PU HYGEIA PRESS CORRIDORI MARINELLA PI QUARTU SANT ELENA PA VIA MONTECATINI 53, QUARTU SANT ELENA, CA09045, ITALY SN 2281-0692 J9 J PEDIATR NEONATAL I JI J. Pediatr. Neonatal Individ. Med. PD OCT PY 2015 VL 4 IS 2 AR e040239 DI 10.7363/040239 PG 8 WC Pediatrics SC Pediatrics GA CY5WR UT WOS:000366478800014 ER PT J AU Nikolaou, NI Arntz, HR Bellou, A Beygui, F Bossaert, LL Cariou, A AF Nikolaou, Nikolaos I. Arntz, Hans-Richard Bellou, Abdelouahab Beygui, Farzin Bossaert, Leo L. Cariou, Alain CA Initial Management Acute Coronary TI European Resuscitation Council Guidelines for Resuscitation 2015 Section 8. Initial management of acute coronary syndromes SO RESUSCITATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT-ELEVATION; HOSPITAL CARDIAC-ARREST; ASSOCIATION TASK-FORCE; ACUTE CHEST-PAIN; RANDOMIZED CONTROLLED-TRIAL; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ACCELERATED DIAGNOSTIC PROTOCOL; MOLECULAR-WEIGHT HEPARIN; PLACEBO-CONTROLLED TRIAL C1 [Nikolaou, Nikolaos I.] Konstantopouleio Gen Hosp, Dept Cardiol, Athens, Greece. [Arntz, Hans-Richard] Charite, Dept Emergency Med, D-13353 Berlin, Germany. [Bellou, Abdelouahab] Univ Rennes, Rennes, France. [Bellou, Abdelouahab] Harvard Univ, Sch Med, Dept Emergency Med, Beth Israel Deaconnes Med Ctr, Boston, MA USA. [Beygui, Farzin] Caen Univ Hosp, Intervent Cardiol Unit, Caen, France. [Bossaert, Leo L.] Univ Antwerp, Dept Med & Hlth Sci, B-2020 Antwerp, Belgium. [Cariou, Alain] Cochin Univ Hosp, APHP, Med Intens Care Unit, Paris, France. [Cariou, Alain] Paris Descartes Univ, Paris, France. RP Nikolaou, NI (reprint author), Konstantopouleio Gen Hosp, Dept Cardiol, Athens, Greece. EM nikosnik@otenet.gr FU Fourier trial-AMGEN FX Nikolaos Nikolaou Research grant Fourier trial-AMGEN NR 186 TC 15 Z9 15 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD OCT PY 2015 VL 95 BP 264 EP 277 DI 10.1016/j.resuscitation.2015.07.030 PG 14 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA CY7IA UT WOS:000366580600017 PM 26477416 ER PT J AU Kreydin, EI Kim, MM Barrisford, GW Rodriguez, D Sanchez, A Santiago-Lastra, Y Ko, DSC AF Kreydin, Evgeniy I. Kim, Michelle M. Barrisford, Glen W. Rodriguez, Dayron Sanchez, Alejandro Santiago-Lastra, Yahir Ko, Dicken S. C. TI Urinary Lignans Are Associated With Decreased Incontinence in Postmenopausal Women SO UROLOGY LA English DT Article ID NUTRITION EXAMINATION SURVEY; RISK-FACTORS; NATIONAL-HEALTH; PREVALENCE; ESTROGEN; MEN; PHYTOESTROGENS; ISOFLAVONES; SERUM AB OBJECTIVE To examine the association between urinary phytoestrogens and self-reported urinary incontinence in postmenopausal women in the United States using a large, cross-sectional, population-based cohort survey. METHODS Data were analyzed for 1789 postmenopausal women aged 50 years or older who participated in one of the 2001-2010 cycles of National Health and Nutrition Examination Survey and underwent measurement of 4 isoflavone (soy derived) and 2 lignan (flax derived) phytoestrogens in their urine. Incontinence was defined as self-reported stress, urge, other, or mixed incontinence. Urine phytoestrogen concentrations were examined in weighted, multivariate logistic regression models for association with each of the lower urinary tract symptoms. All models were adjusted for age, body mass index, diabetes, race, smoking, and parity. RESULTS Increasing urine concentrations of the lignan phytoestrogen enterodiol was associated with decreased likelihood of urge (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.85-0.99), mixed (OR, 0.90; 95% CI, 0.82-0.98), and other (OR, 0.90; 95% CI, 0.81-0.99) incontinence, whereas increasing urine concentrations of the lignan phytoestrogen enterolactone was associated with decreased likelihood of urge (OR, 0.92; 95% CI, 0.86-0.99) and mixed (OR, 0.91; 95% CI, 0.84-0.99) incontinence. No association was observed between any isoflavone phytoestrogens and types of incontinence. CONCLUSION This study demonstrates that lignan phytoestrogens may have a protective effect against incontinence in postmenopausal women. Prospective clinical and laboratory studies are warranted to investigate the mechanism of this relationship. (C) 2015 Elsevier Inc. C1 [Kreydin, Evgeniy I.; Kim, Michelle M.; Barrisford, Glen W.; Rodriguez, Dayron; Sanchez, Alejandro; Santiago-Lastra, Yahir; Ko, Dicken S. C.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Kreydin, EI (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. EM kreydin@post.harvard.edu NR 25 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD OCT PY 2015 VL 86 IS 4 BP 716 EP 720 DI 10.1016/j.urology.2015.07.024 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA CY5RG UT WOS:000366464300015 PM 26232691 ER PT J AU Viswanathan, A Macklin, EA Betensky, R Hyman, B Smith, EE Blacker, D AF Viswanathan, Anand Macklin, Eric A. Betensky, Rebecca Hyman, Bradley Smith, Eric E. Blacker, Deborah TI The Influence of Vascular Risk Factors and Stroke on Cognition in Late Life Analysis of the NACC Cohort SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE vascular risk factors; cognitive decline; Framingham stroke risk profile; cerebrovascular disease; stroke; cognitively normal ID SMALL-VESSEL DISEASE; INCIDENT ALZHEIMER-DISEASE; MIDLIFE BLOOD-PRESSURE; ELDERLY MALE TWINS; DATA SET UDS; ATRIAL-FIBRILLATION; DIABETES-MELLITUS; PROCESSING SPEED; APOE GENOTYPE; DEMENTIA AB Objective:Vascular risk factors in mid-life predict late life cognitive decline in previously normal populations. We sought to investigate the contribution of vascular risk factors in late life to cognitive decline in a cohort of normal elderly individuals.Methods:Cognitively normal subjects were identified from the longitudinal cohort of participants in the National Alzheimer Coordinating Center (NACC) database (n=2975). The association between a composite score of vascular risk factors (based on the Framingham Stroke Risk Profile) and cognitive function was tested at baseline visit and estimated in longitudinal analyses using linear mixed-effects models.Results:Total vascular risk factor burden was associated with worse cognitive performance at baseline and faster decline longitudinally in univariate analyses but only with worse WAIS digit symbol performance in cross-sectional (estimate=-0.266 units/1 unit of Framingham Stroke Risk Profile Score; 95% confidence interval, -0.380 to -0.153; P<0.001) and longitudinal (estimate=-0.034 units/1 unit of Framingham Stroke Risk Profile Score/year; 95% confidence interval, -0.055 to -0.012; P=0.002) analyses after adjusting for age, education, and APOE genotype. Individuals with history of stroke performed significantly worse on the trails B, category fluency, and Boston naming tests in cross-sectional analyses and in delayed logical memory and digit span backwards in longitudinal analyses.Conclusions:Although the modified Framingham Stroke Risk Profile in late-life predicts rate of decline on selective neurocognitive measures in previously normal elderly individuals, age appears to be the strongest risk factor for cognitive impairment in this population. History of stroke independently influences rate of cognitive decline in these individuals. C1 [Viswanathan, Anand; Hyman, Bradley] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Viswanathan, Anand; Blacker, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Viswanathan, Anand] Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Macklin, Eric A.; Betensky, Rebecca] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Hyman, Bradley; Blacker, Deborah] Massachusetts Gen Hosp, Massachusetts Alzheimer Dis Res Ctr ADRC, Boston, MA 02114 USA. [Hyman, Bradley; Blacker, Deborah] Harvard Univ, Sch Med, Boston, MA USA. [Betensky, Rebecca] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB, Canada. RP Viswanathan, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program,Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM aviswanathan1@partners.org OI Macklin, Eric/0000-0003-1618-3502 FU NIH [5P50AG005134-28, U01 AG016976-13]; Harvard NeuroDiscovery Center FX Supported by NIH grants 5P50AG005134-28 (Massachusetts General Hospital), U01 AG016976-13 (University of Washington), and the Harvard NeuroDiscovery Center. NR 47 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2015 VL 29 IS 4 BP 287 EP 293 DI 10.1097/WAD.0000000000000080 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA CX4TH UT WOS:000365692700003 PM 25626633 ER PT J AU Marquez-Malaver, F Kekre, N Porras, RP Barrigon, DC Sanchez, JLP Sanfeliu, AE Parra, ML Vercet, CS Armand, P Simon, JAP AF Marquez-Malaver, F. Kekre, N. Parody Porras, R. Caballero Barrigon, D. Pinana Sanchez, J. L. Esquirol Sanfeliu, A. Lopez Parra, M. Solano Vercet, C. Armand, P. Perez Simon, J. A. TI COMPARISON OF TREATMENT REGIMENS OF REDUCED INTENSITY CONDITIONING IN ALLOGENIC TRANSPLANT OF HEMATOPOIETIC PROGENITORS FOR LYMPHOMA SO HAEMATOLOGICA LA Spanish DT Meeting Abstract CT 57th National Congress of the Spanish-Society-of-Hematology-and-Hemotherapy CY OCT 22-24, 2015 CL Valencia, SPAIN SP Spanish Soc Hematol & Hemotherapy, Novartis Oncol, Celgene, Takeda Oncol, Bristol Myers Squibb, Janssen, Amgen Oncol, Roche, Gilead, GlaxoSmithKline, Alexion, Ariad C1 [Marquez-Malaver, F.; Parody Porras, R.; Perez Simon, J. A.] Hospital Univ Virgen del Rocio, Inst Biomed IbiS, Seville, Spain. [Kekre, N.; Armand, P.] Dana Farber Canc Inst, Boston, MA USA. [Caballero Barrigon, D.; Lopez Parra, M.] Hosp Univ Slamanca, Salamanca, Spain. [Pinana Sanchez, J. L.; Solano Vercet, C.] Hosp Clin Univ Valencia, Valencia, Spain. [Esquirol Sanfeliu, A.] Hosp Santa Creu & Sant Pau, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD OCT PY 2015 VL 100 SU 4 MA CO-080 BP 53 EP 54 PG 2 WC Hematology SC Hematology GA CX5XX UT WOS:000365776900090 ER PT J AU Yurgelun, MB Hiller, E Garber, JE AF Yurgelun, Matthew B. Hiller, Elaine Garber, Judy E. TI Population-Wide Screening for Germline BRCA1 and BRCA2 Mutations: Too Much of a Good Thing? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID UNSELECTED JEWISH WOMEN; CANCER-RISK ASSESSMENT; OVARIAN-CANCER; ASHKENAZI JEWS; HEREDITARY BREAST; FOUNDER MUTATIONS; AMERICAN SOCIETY; REDUCING SURGERY; UNITED-STATES; CARRIERS C1 [Yurgelun, Matthew B.; Hiller, Elaine; Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yurgelun, Matthew B.; Garber, Judy E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yurgelun, MB (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 52 TC 6 Z9 6 U1 1 U2 7 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 OCT 1 PY 2015 VL 33 IS 28 BP 3092 EP + DI 10.1200/JCO.2015.60.8596 PG 5 WC Oncology SC Oncology GA CX9IJ UT WOS:000366018600007 PM 26282646 ER PT J AU Lin, CC Bruinooge, SS Kirkwood, MK Olsen, C Jemal, A Bajorin, D Giordana, SH Goldstein, M Guadagnolo, BA Kosty, M Hopkins, S Yu, JB Arnone, A Hanley, A Stevens, S Hershman, DI AF Lin, Chun Chieh Bruinooge, Suanna S. Kirkwood, M. Kelsey Olsen, Christine Jemal, Ahmedin Bajorin, Dean Giordana, Sharon H. Goldstein, Michael Guadagnolo, B. Ashleigh Kosty, Michael Hopkins, Shane Yu, James B. Arnone, Anna Hanley, Amy Stevens, Stephanie Hershman, Dawn I. TI Association Between Geographic Access to Cancer Care, Insurance, and Receipt of Chemotherapy: Geographic Distribution of Oncologists and Travel Distance SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL COMORBIDITY INDEX; III COLORECTAL-CANCER; COLON-CANCER; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; HEALTH-INSURANCE; LUNG-CANCER; NSABP C-07; DATA-BASE; STAGE-II AB Purpose Geographic access to care may be associated with receipt of chemotherapy but has not been fully examined. This study sought to evaluate the association between density of oncologists and travel distance and receipt of adjuvant chemotherapy for colon cancer within 90 days of colectomy. Patients and Methods Patients in the National Cancer Data Base with stage III colon cancer, diagnosed between 2007 and 2010, and age 18 to 80 years were selected. Generalized estimating equation clustering by hospital service area was conducted to examine the association between geographic access and receipt of oncology services, controlling for patient sociodemographic and clinical characteristics. Results Of 34,694 patients in the study cohort, 75.7% received adjuvant chemotherapy within 90 days of colectomy. Compared with travel distance less than 12.5 miles, patients who traveled 50 to 249 miles (odds ratio [OR], 0.87; P = .009) or 250 miles (OR, 0.36; P < .001) had decreased likelihood of receiving adjuvant chemotherapy. Density level of oncologists was not statistically associated with receipt of adjuvant chemotherapy (low v high density: OR, 0.98; P = .77). When stratifying analyses by insurance status, non-privately insured patients who resided in areas with low density of oncologists were less likely to receive adjuvant chemotherapy (OR, 0.85; P = .03). Conclusion Increased travel burden was associated with a decreased likelihood of receiving adjuvant chemotherapy, regardless of insurance status. Patients with nonprivate insurance who resided in low-density oncologist areas were less likely to receive adjuvant chemotherapy. If these findings are validated prospectively, interventions to decrease geographic barriers may improve the timeliness and quality of colon cancer treatment. (C) 2015 by American Society of Clinical Oncology C1 [Lin, Chun Chieh; Jemal, Ahmedin] Amer Canc Soc, Atlanta, GA 30303 USA. [Bruinooge, Suanna S.; Kirkwood, M. Kelsey; Hanley, Amy] Amer Soc Clin Oncol, Alexandria, VA USA. [Arnone, Anna; Stevens, Stephanie] Amer Soc Radiat Oncol, Fairfax, VA USA. [Olsen, Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldstein, Michael] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bajorin, Dean] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hershman, Dawn I.] Columbia Univ, Med Ctr, New York, NY USA. [Giordana, Sharon H.; Guadagnolo, B. Ashleigh] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kosty, Michael] Scripps Clin, La Jolla, CA 92037 USA. [Hopkins, Shane] William R Bliss Canc Ctr, Ames, IA USA. [Yu, James B.] Yale Univ, Sch Med, New Haven, CT USA. RP Lin, CC (reprint author), Amer Canc Soc, 250 Williams St, Atlanta, GA 30303 USA. EM anna.lin@cancer.org FU American Cancer Society Intramural Research Funding FX Supported by American Cancer Society Intramural Research Funding. NR 45 TC 10 Z9 10 U1 3 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 OCT 1 PY 2015 VL 33 IS 28 BP 3177 EP + DI 10.1200/JCO.2015.61.1558 PG 14 WC Oncology SC Oncology GA CX9IJ UT WOS:000366018600018 PM 26304878 ER PT J AU Gounder, MM Nayak, L Sahebjam, S Muzikansky, A Sanchez, AJ Desideri, S Ye, XB Ivy, SP Nabors, LB Prados, M Grossman, S DeAngelis, LM Wen, PY AF Gounder, Mrinal M. Nayak, Lakshmi Sahebjam, Solmaz Muzikansky, Alona Sanchez, Armando J. Desideri, Serena Ye, Xiaobu Ivy, S. Percy Nabors, L. Burt Prados, Michael Grossman, Stuart DeAngelis, Lisa M. Wen, Patrick Y. TI Evaluation of the Safety and Benefit of Phase I Oncology Trials for Patients With Primary CNS Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECURRENT MALIGNANT GLIOMA; HIGH-GRADE GLIOMAS; BRAIN METASTASES; CLINICAL-TRIALS; SOLID TUMORS; ATRASENTAN; INHIBITOR; TOXICITY; CANCER; PHARMACOKINETICS AB Purpose Patients with high-grade gliomas (HGG) are frequently excluded from first-in-human solid tumor trials because of perceived poor prognosis, excessive toxicities, concomitant drug interactions, and poor efficacy. We conducted an analysis of outcomes from select, single-agent phase I studies in patients with HGG. We compared outcomes to pooled analysis of published studies in solid tumors with various molecular and cytotoxic drugs evaluated as single agents or as combinations. Patient and Methods Individual records of patients with recurrent HGG enrolled onto Adult Brain Tumor Consortium trials of single-agent, cytotoxic or molecular agents from 2000 to 2008 were analyzed for baseline characteristics, toxicities, responses, and survival. Results Our analysis included 327 patients with advanced, refractory HGG who were enrolled onto eight trials involving targeted molecular (n = 5) and cytotoxic (n = 3) therapies. At enrollment, patients had a median Karnofsky performance score of 90 and median age of 52 years; 62% were men, 63% had glioblastoma, and the median number of prior systemic chemotherapies was one. Baseline laboratory values were in an acceptable range to meet eligibility criteria. Patients were on the study for a median of two cycles (range, < one to 56 cycles), and 96% were evaluable for primary end points. During cycle 1, grade >= 3 nonhematologic and grade 4 hematologic toxicities were 5% (28 of 565 adverse events) and 0.9% (five of 565 adverse events), respectively, and 66% of these occurred at the highest dose level. There was one death attributed to drug. Overall response rate (complete and partial response) was 5.5%. Median progression-free and overall survival times were 1.8 and 6 months, respectively. Conclusion Patients with HGG who meet standard eligibility criteria may be good candidates for solid tumor phase I studies with single-agent molecular or cytotoxic drugs with favorable preclinical rationale and pharmacokinetic properties in this population. (C) 2015 by American Society of Clinical Oncology C1 [Gounder, Mrinal M.; Sanchez, Armando J.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Gounder, Mrinal M.; Sanchez, Armando J.; DeAngelis, Lisa M.] Weil Cornell Med Sch, New York, NY USA. [Nayak, Lakshmi; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Nayak, Lakshmi; Muzikansky, Alona; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sahebjam, Solmaz] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Desideri, Serena; Ye, Xiaobu; Grossman, Stuart] Johns Hopkins Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Nabors, L. Burt] Univ Alabama Birmingham, Birmingham, AL USA. [Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Gounder, MM (reprint author), Mem Sloan Kettering Canc Ctr, Dev Therapeut Serv, 300 E 66th St BAIC 1075, New York, NY 10065 USA. EM gounderm@mskcc.org FU Cortice Biosciences (Inst); Merck (Inst); Genentech/Roche (Inst); Erimos Pharmaceuticals (Inst); AstraZeneca; Agios; Angiochem; Exelixis; Genentech/Roche; GlaxoSmithKline; Karyopharm Therapeutics; Merck; Novartis; Sanofi; Vascular Biogenics FX Cortice Biosciences (Inst), Merck (Inst); Genentech/Roche (Inst); Erimos Pharmaceuticals (Inst); AstraZeneca, Agios, Angiochem, Exelixis, Genentech/Roche, GlaxoSmithKline, Karyopharm Therapeutics, Merck, Novartis, Sanofi, Vascular Biogenics NR 40 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 OCT 1 PY 2015 VL 33 IS 28 BP 3186 EP + DI 10.1200/JCO.2015.61.1525 PG 9 WC Oncology SC Oncology GA CX9IJ UT WOS:000366018600019 PM 26282642 ER PT J AU Steensma, DP AF Steensma, David P. TI Key Opinion Leaders SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana Bldg,Room 2037, Boston, MA 02115 USA. EM dsteensma@partners.org NR 2 TC 2 Z9 2 U1 2 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 OCT 1 PY 2015 VL 33 IS 28 BP 3213 EP + DI 10.1200/JCO.2015.63.1275 PG 3 WC Oncology SC Oncology GA CX9IJ UT WOS:000366018600022 PM 26261246 ER PT J AU Randall, TC Salicrup, LA Luciani, S Trimble, EL AF Randall, Thomas C. Salicrup, Luis A. Luciani, Silvana Trimble, Edward L. TI HPV Testing in Resource-Limited Settings: How Can We Reach the Next Level of Cervical Cancer Screening in Latin America and the Caribbean? SO ONCOLOGIST LA English DT Editorial Material ID MORTALITY; INDIA C1 [Randall, Thomas C.] Dana Farber Harvard Canc Ctr, Global Oncol Initiat, Boston, MA USA. [Salicrup, Luis A.; Trimble, Edward L.] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA. [Luciani, Silvana] Pan Amer Hlth Org, Canc Prevent & Control, Washington, DC USA. RP Randall, TC (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St,Gates 520 B, Boston, MA 02108 USA. EM trandall@mgh.harvard.edu NR 9 TC 0 Z9 0 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD OCT PY 2015 VL 20 IS 10 BP 1101 EP 1104 DI 10.1634/theoncologist.2015-0201 PG 4 WC Oncology SC Oncology GA CX9QX UT WOS:000366041500001 PM 26330459 ER PT J AU Mundy, EA Weber, M Rauch, SL Killgore, WDS Simon, NM Pollack, MH Rosso, IM AF Mundy, Elizabeth A. Weber, Mareen Rauch, Scott L. Killgore, William D. S. Simon, Naomi M. Pollack, Mark H. Rosso, Isabelle M. TI ADULT ANXIETY DISORDERS IN RELATION TO TRAIT ANXIETY AND PERCEIVED STRESS IN CHILDHOOD SO PSYCHOLOGICAL REPORTS LA English DT Article ID SEROTONIN TRANSPORTER GENE; EARLY-LIFE STRESS; BEHAVIORAL-INHIBITION; PSYCHIATRIC-DISORDERS; MEMORY BIAS; FOLLOW-UP; DEPRESSION; EVENTS; MALTREATMENT; SYSTEM AB It is well established that objective early life stressors increase risk for anxiety disorders and that environmental stressors interact with dispositional factors such as trait anxiety. There is less information on how subjective perception of stress during childhood relates to later clinical anxiety. This study tested whether childhood perceived stress and trait anxiety were independently and interactively associated with adult anxiety disorders. Forty-seven adults diagnosed with anxiety disorders (M age = 34 yr., SD = 11) and 29 healthy participants (M = 33 yr., SD = 13) completed the adult Perceived Stress Scale, the State-Trait Anxiety Inventory, and the Global Perceived Early Life Events Scale as a measure of perceived stress during childhood. In a logistic regression model, high childhood perceived stress (beta = 0.64) and trait anxiety (beta = 0.11) were associated with significantly greater odds of adult anxiety disorder. The association between childhood perceived stress and adult anxiety remained signifi cant when controlling for adult perceived stress. These findings suggest that children's perception of stress in their daily lives may be an important target of intervention to prevent the progression of stress into clinically signifi cant anxiety. C1 [Mundy, Elizabeth A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Weber, Mareen; Rauch, Scott L.; Killgore, William D. S.; Rosso, Isabelle M.] McLean Hosp, Ctr Depress Anxiety & Stress Res, Belmont, MA 02478 USA. [Weber, Mareen; Rauch, Scott L.; Killgore, William D. S.; Rosso, Isabelle M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Pollack, Mark H.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. RP Rosso, IM (reprint author), McLean Hosp, Anxiety & Traumat Stress Dis Lab, 115 Mill St,Mailstop 334, Belmont, MA 02478 USA. EM irosso@hms.harvard.edu NR 68 TC 0 Z9 1 U1 5 U2 8 PU AMMONS SCIENTIFIC, LTD PI MISSOULA PA PO BOX 9229, MISSOULA, MT 59807-9229 USA SN 0033-2941 J9 PSYCHOL REP JI Psychol. Rep. PD OCT PY 2015 VL 117 IS 2 BP 473 EP 489 DI 10.2466/02.10.PR0.117c17z6 PG 17 WC Psychology, Multidisciplinary SC Psychology GA CY4NR UT WOS:000366385400011 PM 26340052 ER PT J AU Baselga, J Bhardwaj, N Cantley, LC DeMatteo, R DuBois, RN Foti, M Gapstur, SM Hahn, WC Helman, LJ Jensen, RA Paskett, ED Lawrence, TS Lutzker, SG Szabo, E AF Baselga, Jose Bhardwaj, Nina Cantley, Lewis C. DeMatteo, Ronald DuBois, Raymond N. Foti, Margaret Gapstur, Susan M. Hahn, William C. Helman, Lee J. Jensen, Roy A. Paskett, Electra D. Lawrence, Theodore S. Lutzker, Stuart G. Szabo, Eva TI AACR Cancer Progress Report 2015 SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN-PAPILLOMAVIRUS VACCINATION; ADVANCED BREAST-CANCER; CELL LUNG-CANCER; BODY-MASS INDEX; UNITED-STATES; COLORECTAL-CANCER; ADVANCED MELANOMA; AMERICAN ASSOCIATION; PANCREATIC-CANCER; POLICY STATEMENT C1 [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Bhardwaj, Nina] Mt Sinai Med Ctr, Ctr Sci & Med, Immunotherapy, New York, NY USA. [Cantley, Lewis C.] Weill Cornell Med Coll, Sandra & Edward Meyer Canc Ctr, New York, NY USA. [DeMatteo, Ronald] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY USA. [DeMatteo, Ronald] Mem Sloan Kettering Canc Ctr, Div Gen Surg Oncol, New York, NY USA. [DuBois, Raymond N.] Arizona State Univ, Biodesign Inst, Tempe, AZ USA. [Foti, Margaret] Am Assoc Canc Res, Philadelphia, PA USA. [Gapstur, Susan M.] Am Canc Soc, Epidemiol Res Program, Atlanta, GA USA. [Hahn, William C.] Dana Farber Canc Inst, Div Mol & Cellular Oncol, Boston, MA USA. [Helman, Lee J.] NCI, Clin Res, Bethesda, MD USA. [Jensen, Roy A.] Univ Kansas, Canc Ctr, Kansas City, KS USA. [Paskett, Electra D.] Ohio State Univ, Comprehens Canc Ctr, Populat Sci Dept, Columbus, OH USA. [Lawrence, Theodore S.] Univ Michigan, Canc Ctr, Ann Arbor, MI USA. [Lawrence, Theodore S.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI USA. [Lutzker, Stuart G.] Genentech Inc, Clin Dev, BioOncol Exploratory, San Francisco, CA USA. [Szabo, Eva] NCI, Lung & Upper Aerodigest, Canc Res Grp, Potomac, MD USA. RP Baselga, J (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [P30 CA008748] NR 167 TC 1 Z9 1 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2015 VL 21 SU 19 BP S1 EP S128 DI 10.1158/1078-0432.CCR-15-1846 PG 128 WC Oncology SC Oncology GA CV7UE UT WOS:000364480100010 PM 26429991 ER PT J AU Yoon, WJ Brugge, WR AF Yoon, Won Jae Brugge, William R. TI The safety of endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesions SO ENDOSCOPIC ULTRASOUND LA English DT Review DE Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA); pancreatic cyst; safety ID GASTROENTEROLOGY EUROPEAN-SOCIETY; EUS-FNA; DIAGNOSIS; TUMOR; COMPLICATIONS; NEOPLASMS; GUIDELINES; MANAGEMENT; CANCER AB Endoscopic ultrasound (EUS) is widely used in the evaluation of various pancreatic diseases including pancreatic cystic lesions (PCLs). EUS-guided fine-needle aspiration (EUS-FNA) of PCLs provides cyst fluid, which is used for the differentiation of PCLs. EUS-FNA of PCLs is a safe procedure with a low complication rate. Contrary to the concerns expressed by some investigators, preoperative EUS-FNA of mucinous PCLs is unlikely to increase the frequency of postoperative peritoneal seeding. C1 [Yoon, Won Jae] Inje Univ, Coll Med, Seoul Paik Hosp, Dept Internal Med, Seoul, South Korea. [Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM Brugge.William@mgh.harvard.edu NR 27 TC 3 Z9 3 U1 0 U2 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 2303-9027 EI 2226-7190 J9 ENDOSC ULTRASOUND JI Endosc. Ultrasound PD OCT-DEC PY 2015 VL 4 IS 4 BP 289 EP 292 DI 10.4103/2303-9027.170408 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CX5WB UT WOS:000365772100004 PM 26643695 ER PT J AU Bonaca, MP O'Malley, RG Murphy, SA Jarolim, P Conrad, MJ Braunwald, E Sabatine, MS Morrow, DA AF Bonaca, Marc P. O'Malley, Ryan G. Murphy, Sabina A. Jarolim, Petr Conrad, Michael J. Braunwald, Eugene Sabatine, Marc S. Morrow, David A. TI Prognostic performance of a high-sensitivity assay for cardiac troponin I after non-ST elevation acute coronary syndrome: Analysis from MERLIN-TIMI 36 SO EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE LA English DT Article DE Cardiac troponin; troponin; acute coronary syndrome; prognosis ID MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; UNSTABLE ANGINA; HEART-DISEASE; RECLASSIFICATION; ASSOCIATION; MORTALITY; ABILITY AB Background: Newer troponin assays offer the ability to quantify circulating troponin levels at an order of magnitude lower than contemporary assays, fueling continued debate over the prognostic implications of very low-level increases in concentration. We evaluated the prognostic implications of low-level increases in cardiac troponin I (cTnI) using an investigational single-molecule high-sensitivity assay in patients with acute coronary syndrome (ACS). Methods: We measured cTnI using both a high-sensitivity troponin I (hsTnI) assay (Erenna, Singulex, 99th percentile 9 pg/ml) and a current generation sensitive assay (TnI-Ultra, Siemens, 99th percentile 40 pg/ml) at baseline in 1807 patients with non-ST elevation ACS and compared their prognostic ability for adverse cardiovascular events at 30 days and one year. Results: Among patients with TnI-Ultra<99th percentile, patients with elevated hsTnI (>= 9 pg/ml) had a significantly higher risk than patients with hsTnI<9 pg/ml: cardiovascular death (CVD) or myocardial infarction (MI) at one year (7.0% vs 3.8%; p<0.001, hazard ratio (HR) 2.05, confidence interval (CI) 1.23-3.41); including a higher risk of CVD (3.5% vs 1.5%, p<0.001) and MI (5.0% vs 2.8%, p<0.001) individually. This higher risk of CVD/MI was independent of clinical risk stratification using the TIMI Risk Score (adj. HR 1.76, CI 1.05-2.90). Moreover, hsTnI showed a trend toward a gradient of risk even below the hsTnI 99 percentile. Conclusions: Low-level cardiac troponin detected using a single-molecule technique, below the cutpoint of a contemporary sensitive assay, identified a significant gradient of risk. These findings support the prognostic relevance of low-level cardiac troponin elevation with increasingly sensitive assays in patients with ACS. C1 [Bonaca, Marc P.; O'Malley, Ryan G.; Murphy, Sabina A.; Braunwald, Eugene; Sabatine, Marc S.; Morrow, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Jarolim, Petr; Conrad, Michael J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org FU NHLBI NIH HHS [RC1HL099692]; PHS HHS [HHSN268201000033C] NR 20 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 2048-8726 EI 2048-8734 J9 EUR HEART J-ACUTE CA JI Eur. Heart J.-Acute Cardiovasc. Care PD OCT PY 2015 VL 4 IS 5 BP 431 EP 440 DI 10.1177/2048872614564081 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX3PZ UT WOS:000365612800006 PM 25538086 ER PT J AU Cavender, MA Gibson, CM Braunwald, E Wiviott, SD Murphy, SA Kato, ET Plotnikov, AN Amuchastegui, M Ophuis, TO van Hessen, M Mega, JL AF Cavender, Matthew A. Gibson, C. Michael Braunwald, Eugene Wiviott, Stephen D. Murphy, Sabina A. Kato, Eri Toda Plotnikov, Alexei N. Amuchastegui, Marcos Ophuis, Ton Oude van Hessen, Maarten Mega, Jessica L. TI The effect of rivaroxaban on myocardial infarction in the ATLAS ACS 2 - TIMI 51 trial SO EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE LA English DT Article DE Anti-thrombotic therapy; acute coronary syndrome; secondary prevention ID ACUTE CORONARY SYNDROME; ST-SEGMENT ELEVATION; UNIVERSAL DEFINITION; AMERICAN-COLLEGE; DOUBLE-BLIND; MORTALITY; THROMBOLYSIS; INTERVENTION; GUIDELINES; MANAGEMENT AB Aims: Rivaroxaban reduces cardiovascular death, myocardial infarction (MI), or stroke in patients following acute coronary syndrome (ACS). We aimed to characterize the specific effects of rivaroxaban on the size and type of MI. Methods: The Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 (ATLAS ACS 2-TIMI 51) study randomized 15,526 patients with a recent ACS to rivaroxaban 2.5 mg BID, rivaroxaban 5 mg BID, or placebo. An independent clinical events committee adjudicated each MI that occurred during the study and further classified them based on type. Data are presented as two-year Kaplan-Meier event rates and hazard ratios (HRs) and 95% confidence intervals (CI). Results: In total, 665 patients experienced a post-randomization MI. The majority (n=535, 80.5%) were spontaneous (Type 1) events. Rivaroxaban reduced spontaneous MI when compared with placebo (4.4% vs 5.7%, HR 0.80, 95% 0.67-0.95, p=0.01), and there were directionally consistent reductions with both the 2.5 mg BID (4.7% vs 5.7%, HR 0.84, 95% 0.68-1.02, p=0.08) and 5 mg BID doses (4.1% vs 5.7%, HR 0.77, 95% 0.62-0.94, p=0.01) as compared with placebo. Rivaroxaban reduced MI with large elevations in troponin or creatine kinase-MB (CK-MB) fraction (1.8% vs 2.4%, HR 0.73, 95% CI 0.56-0.96, p=0.03) and STEMI events (1.7% vs 2.5%, HR 0.74, 95% CI 0.56-0.99, p=0.04). Conclusions: In patients stabilized and followed after ACS, the majority of MIs that occur are spontaneous and rivaroxaban significantly reduced the incidence of these events. Notably, rivaroxaban reduced MIs with extensive biomarker release and ST-segment elevation. C1 [Cavender, Matthew A.; Gibson, C. Michael; Braunwald, Eugene; Wiviott, Stephen D.; Murphy, Sabina A.; Kato, Eri Toda; Mega, Jessica L.] Brigham & Womens Hosp, Heart & Vasc Ctr, TIMI Study Grp, Boston, MA 02115 USA. [Cavender, Matthew A.; Gibson, C. Michael; Braunwald, Eugene; Wiviott, Stephen D.; Murphy, Sabina A.; Kato, Eri Toda; Mega, Jessica L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Plotnikov, Alexei N.] Janssen Res & Dev LLC, Raritan, NJ USA. [Amuchastegui, Marcos] Hosp Privado, Ctr Med Cordoba, La Plata, Argentina. [Ophuis, Ton Oude] Canisius Wilhelmina Ziekenhuis, Dept Cardiol, Nijmegen, Netherlands. [van Hessen, Maarten] Groene Hart Hosp, Dept Cardiol, Nijmegen, Netherlands. RP Mega, JL (reprint author), TIMI Study Grp, 350 Longwood Ave,First Floor Off, Boston, MA 02115 USA. EM jmega@partners.org NR 24 TC 3 Z9 4 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 2048-8726 EI 2048-8734 J9 EUR HEART J-ACUTE CA JI Eur. Heart J.-Acute Cardiovasc. Care PD OCT PY 2015 VL 4 IS 5 BP 468 EP 474 DI 10.1177/2048872614554109 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX3PZ UT WOS:000365612800010 PM 25318481 ER PT J AU Abed, S Tubsuwan, A Chaichompoo, P Park, IH Pailleret, A Benyoucef, A Tosca, L De Dreuzy, E Paulard, A Granger-Locatelli, M Relouzat, F Prost, S Tachdjian, G Fucharoen, S Daley, GQ Payen, E Chretien, S Leboulch, P Maouche-Chretien, L AF Abed, Soumeya Tubsuwan, Alisa Chaichompoo, Porntip Park, In Hyun Pailleret, Alice Benyoucef, Aissa Tosca, Lucie De Dreuzy, Edouard Paulard, Anais Granger-Locatelli, Marine Relouzat, Francis Prost, Stephane Tachdjian, Gerard Fucharoen, Suthat Daley, George Q. Payen, Emmanuel Chretien, Stany Leboulch, Philippe Maouche-Chretien, Leila TI Transplantation of Macaca cynomolgus iPS-derived hematopoietic cells in NSG immunodeficient mice SO HAEMATOLOGICA LA English DT Letter DE Nonhuman primate; Induced pluripotent stem cells; Engraftment of cy-iPSC-derived hematopoietic cells ID PLURIPOTENT STEM-CELLS; ADULT; BLOOD; FIBROBLASTS; INDUCTION C1 [Abed, Soumeya; Tubsuwan, Alisa; Chaichompoo, Porntip; Pailleret, Alice; Benyoucef, Aissa; De Dreuzy, Edouard; Granger-Locatelli, Marine; Relouzat, Francis; Prost, Stephane; Payen, Emmanuel; Chretien, Stany; Leboulch, Philippe; Maouche-Chretien, Leila] Univ Paris 11, CEA, Inst Emerging Dis & Innovat Therapies iMETI, Orsay, France. [Abed, Soumeya; Tubsuwan, Alisa; Chaichompoo, Porntip; De Dreuzy, Edouard; Payen, Emmanuel; Chretien, Stany; Maouche-Chretien, Leila] INSERM, Paris, France. [Abed, Soumeya; De Dreuzy, Edouard] Univ Paris 07, F-75221 Paris 05, France. [Tubsuwan, Alisa; Chaichompoo, Porntip; Fucharoen, Suthat] Mahidol Univ, Inst Mol Biosci, Thalassemia Res Ctr, Nakhon Pathom, Thailand. [Tubsuwan, Alisa; Chaichompoo, Porntip; Fucharoen, Suthat] Siriraj Hosp, Fac Med, Dept Biochem, Bangkok, Thailand. [Tubsuwan, Alisa; Chaichompoo, Porntip; Fucharoen, Suthat] Mahidol Univ, Fac Sci, Dept Pathobiol, Bangkok 10400, Thailand. [Park, In Hyun; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Park, In Hyun; Daley, George Q.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Benyoucef, Aissa] Inserm U967 CEA DSV IRCM, Fontenay Aux Roses, France. [Tosca, Lucie; Tachdjian, Gerard] Hop Antoine Beclere, AP HP, Serv Histol Embryol Cytogenet, Clamart, France. [Leboulch, Philippe] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Leboulch, Philippe] Harvard Univ, Sch Med, Boston, MA USA. [Paulard, Anais] Bluebirdbio, Cambridge, MA USA. RP Maouche-Chretien, L (reprint author), Univ Paris 11, CEA, Inst Emerging Dis & Innovat Therapies iMETI, Orsay, France. EM leila.maouche@inserm.fr RI PROST, Stephane/I-8362-2015; maouche, leila/E-3887-2017; OI PROST, Stephane/0000-0002-8567-8253; de Dreuzy, Edouard/0000-0002-6941-889X NR 15 TC 3 Z9 3 U1 1 U2 12 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD OCT PY 2015 VL 100 IS 10 BP E428 EP E431 DI 10.3324/haematol.2015.127373 PG 4 WC Hematology SC Hematology GA CX5XM UT WOS:000365775800013 PM 26088930 ER PT J AU Khan, AI Chowdhury, F Leung, DT Larocque, RC Harris, JB Ryan, ET Calderwood, SB Qadri, F AF Khan, Ashraful I. Chowdhury, Fahima Leung, Daniel T. Larocque, Regina C. Harris, Jason B. Ryan, Edward T. Calderwood, Stephen B. Qadri, Firdausi TI Cholera in pregnancy: Clinical and immunological aspects SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Cholera; Immune response; Pregnancy ID VIBRIO-CHOLERAE; IMMUNOGLOBULIN-A; IMMUNE-RESPONSES; BANGLADESH; INFECTION; TOXIN; PROTECTION; WOMEN; LIPOPOLYSACCHARIDE; PREECLAMPSIA AB Background: The objective of this study was to examine the clinical and immunological features of cholera in pregnancy. Methods: Women of reproductive age presenting to the icddr,b Dhaka hospital with cholera, and enrolled as part of a larger cohort study, were tested for pregnancy on admission. We compared initial clinical features and immune responses of pregnant patients with non-pregnant female patients at days 2, 7 and 21 after infection. Results: Among reproductive age women enrolled between January 2001 and May 2006, 9.7% (14/144) were pregnant. The duration of diarrhoea prior to admission tended to be higher in pregnant compared to non-pregnant patients (p=0.08), but other clinical characteristics did not differ. Antibody responses to cholera toxin B subunit (CtxB), toxin-coregulated pilus A (TcpA), Vibrio cholerae lipopolysaccharide (LPS), and serum vibriocidal antibody responses, were comparable between pregnant and non-pregnant patients. There were no deaths among the pregnant cases or non-pregnant controls, and no adverse foetal outcomes, including stillbirths, during 21 days of follow up of pregnant cases. Conclusions: To our knowledge, this is the first report of immune responses in pregnant women with cholera. We found that pregnant woman early in pregnancy has comparable clinical illness and subsequent immune responses compared to non-pregnant women. These findings suggest that the evaluation of safety and immunogenicity of oral cholera vaccines in pregnancy should be an area of future investigations. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license. C1 [Khan, Ashraful I.; Chowdhury, Fahima; Leung, Daniel T.; Qadri, Firdausi] Bangladesh Icddr b, Int Ctr Diarrhoeal Dis Res Bangladesh, Ctr Vaccine Sci, Dhaka 1212, Bangladesh. [Larocque, Regina C.; Harris, Jason B.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Larocque, Regina C.; Harris, Jason B.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Leung, Daniel T.] Univ Utah, Div Infect Dis, Salt Lake City, UT USA. RP Qadri, F (reprint author), Icddr b, Ctr Vaccine Sci, 68 Shahid Tajuddin Ahmed Sarani, Dhaka 1212, Bangladesh. EM fqadri@icddrb.org OI leung, daniel/0000-0001-8401-0801 FU Government of Australia; Government of Bangladesh; Government of Canada; Government of Sweden; Government of UK; [U01 AI058935]; [AI106878]; [K08 AI100923] FX This study was supported by the following grants: U01 AI058935; AI106878 and K08 AI100923. Additionally the study was also supported by core grants to the icddr,b. The icddr,b is thankful to the Governments of Australia, Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support. We wish to thank the study participants and the dedicated clinical, field and laboratory and data management staff of the Cholera Immune Response study. NR 30 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 EI 1878-3511 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD OCT PY 2015 VL 39 BP 20 EP 24 DI 10.1016/j.ijid.2015.08.006 PG 5 WC Infectious Diseases SC Infectious Diseases GA CX3UN UT WOS:000365625000005 PM 26283553 ER PT J AU Chatterjee, NA Singh, JP AF Chatterjee, Neal A. Singh, Jagmeet P. TI Novel Interventional Therapies to Modulate the Autonomic Tone in Heart Failure SO JACC-HEART FAILURE LA English DT Article DE carotid baroreceptor; heart failure; renal denervation; spinal cord stimulation; vagal nerve stimulation ID SPINAL-CORD STIMULATION; SYMPATHETIC-NERVOUS-SYSTEM; TRANSCUTANEOUS ELECTRICAL-STIMULATION; CARDIAC RESYNCHRONIZATION THERAPY; BAROREFLEX ACTIVATION THERAPY; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; CENTRAL SLEEP-APNEA; RENAL DENERVATION; NITRIC-OXIDE AB Heart failure (HF) represents a significant and expanding public health burden associated with increasing prevalence and exponential growth in related health care costs. Contemporary advances in both pharmacological and nonpharmacological therapies have often been restricted in application and benefit. Given the critical role of the autonomic nervous system (ANS) in maintaining cardiovascular homeostasis in the failing heart, there has been increasing interest in the role of ANS modulation as a therapeutic modality in HF. In this review, we highlight the anatomy of the ANS and its role in the pathophysiology of HF, as well as metrics of its assessment. Given the limitations associated with pharmacological ANS modulation, including lack of specificity and medication intolerance, we focus in this review on contemporary nonpharmacological ANS modulation therapies. For each therapy-vagal nerve stimulation, carotid baroreceptor stimulation, spinal cord stimulation, and renal denervation-we review the rationale for modulation, pre-clinical and clinical assessments, as well as procedural considerations and limitations. We conclude by commenting on novel technologies and strategies for ANS modulation on the horizon. (C) 2015 by the American College of Cardiology Foundation. C1 [Chatterjee, Neal A.; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA 02114 USA. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM JSINGH@mgh.harvard.edu FU Boston Scientific; St. Jude Medical; Medtronic; Sorin Group; CardioInsight; Respicardia FX Dr. Singh has received research grants from Boston Scientific, St. Jude Medical, Medtronic, and Sorin Group; and has been a consultant for Boston Scientific, St. Jude Medical, Medtronic, Sorin Group, CardioInsight, and Respicardia. Dr. Chatterjee has reported that he has no relationships relevant to the contents of this paper to disclose. NR 133 TC 7 Z9 7 U1 2 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD OCT PY 2015 VL 3 IS 10 BP 786 EP 802 DI 10.1016/j.jchf.2015.05.008 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4GD UT WOS:000365656200008 PM 26364257 ER PT J AU Graham, ZA Gallagher, PM Cardozo, CP AF Graham, Zachary A. Gallagher, Philip M. Cardozo, Christopher P. TI Focal adhesion kinase and its role in skeletal muscle SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Review DE Focal adhesion kinase; Hypertrophy; Muscle development; Exercise ID SERUM RESPONSE FACTOR; PROTEIN-SYNTHESIS; TYROSINE PHOSPHORYLATION; ALPHA-7-BETA-1 INTEGRIN; QUANTITATIVE CHANGES; RESISTANCE EXERCISE; MYOBLAST FUSION; GENE-EXPRESSION; FACTOR PLAYS; FIBER-TYPE AB Skeletal muscle has a remarkable ability to respond to different physical stresses. Loading muscle through exercise, either anaerobic or aerobic, can lead to increases in muscle size and function while, conversely, the absence of muscle loading stimulates rapid decreases in size and function. A principal mediator of this load-induced change is focal adhesion kinase (FAK), a downstream non-receptor tyrosine kinase that translates the cytoskeletal stress and strain signals transmitted across the cytoplasmic membrane by integrins to activate multiple anti-apoptotic and cell growth pathways. Changes in FAK expression and phosphorylation have been found to correlate to specific developmental states in myoblast differentiation, muscle fiber formation and muscle size in response to loading and unloading. With the capability to regulate costamere formation, hypertrophy and glucose metabolism, FAK is a molecule with diverse functions that are important in regulating muscle cell health. C1 [Graham, Zachary A.; Cardozo, Christopher P.] James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Gallagher, Philip M.] Univ Kansas, Appl Physiol Lab, Lawrence, KS 66045 USA. [Graham, Zachary A.; Cardozo, Christopher P.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Cardozo, Christopher P.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Cardozo, Christopher P.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. RP Cardozo, CP (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM christopher.cardozo@mssm.edu RI Gallagher, Philip/R-9937-2016 OI Gallagher, Philip/0000-0003-4563-4536 FU Veterans Affairs Rehabilitation Research and Development Service [B9212C]; James J. Peters VA Medical Center FX This work was supported by a Veterans Affairs Rehabilitation Research and Development Service grant (B9212C) and the James J. Peters VA Medical Center, where Dr. Cardozo is a member of the Medical-Surgical Service and Dr. Graham is a member of the Research Service. NR 95 TC 2 Z9 2 U1 2 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 EI 1573-2657 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD OCT PY 2015 VL 36 IS 4-5 BP 305 EP 315 DI 10.1007/s10974-015-9415-3 PG 11 WC Cell Biology SC Cell Biology GA CX1HA UT WOS:000365446000003 PM 26142360 ER PT J AU Mahedero, P Calderon, A Arias-Estero, JL Hastie, PA Guarino, AJ AF Mahedero, Pilar Calderon, Antonio Luis Arias-Estero, Jose Hastie, Peter A. Guarino, Anthony J. TI Effects of Student Skill Level on Knowledge, Decision Making, Skill Execution and Game Performance in a Mini-Volleyball Sport Education Season SO JOURNAL OF TEACHING IN PHYSICAL EDUCATION LA English DT Article DE physical education; sport education; skill level; knowledge; game performance ID PHYSICAL-EDUCATION; AMOTIVATED STUDENTS; TASK STRUCTURES; FEEDBACK; MODEL; PLAY; CURRICULUM; TEACHER; UNIT AB The purpose of the paper was to examine the effects of student skill level on knowledge, decision making, skill execution and game performance in a mini-volleyball Sport Education season. Forty-eight secondary school students from two classes participated in a 12 lesson season. Knowledge, decision-making and skill execution (components of game play) were evaluated prior to and on completion of the season. Paired t test analysis showed that the game performance components of decision making and game play achieved significant gains. Further, results of the regression analyses detected that the sigmoidal model was indeed superior to the linear model for (a) skill execution, (b) game play, and (c) knowledge, by explaining 4.0, 2.8, and 3.25 times more of the variance respectively. That is, improvements of the highest and lowest skilled students were less significant than those of more moderate levels. This outcome, accompanied by a lack of general improvement in skill execution, suggests that future research should examine in more detail the progressive development of the tasks and learning experiences incorporated during seasons of Sport Education. C1 [Mahedero, Pilar; Calderon, Antonio; Luis Arias-Estero, Jose] UCAM Catholic Univ Murcia, Murcia, Spain. [Hastie, Peter A.] Auburn Univ, Sch Kinesiol, Auburn, AL 36849 USA. [Guarino, Anthony J.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Calderon, A (reprint author), UCAM Catholic Univ Murcia, Murcia, Spain. EM acluquin@ucam.edu RI Calderon, Antonio/E-5328-2010; OI Calderon, Antonio/0000-0003-1389-9898; Arias-Estero, Jose L./0000-0002-6201-4710 NR 64 TC 2 Z9 2 U1 7 U2 16 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 0273-5024 EI 1543-2769 J9 J TEACH PHYS EDUC JI J. Teach. Phys. Educ. PD OCT PY 2015 VL 34 IS 4 BP 626 EP 641 DI 10.1123/jtpe.2014-0061 PG 16 WC Education & Educational Research; Sport Sciences SC Education & Educational Research; Sport Sciences GA CX2VE UT WOS:000365554100006 ER PT J AU Ryan, RJH Drier, Y Whitton, H Cotton, MJ Kaur, J Issner, R Gillespie, S Epstein, CB Nardi, V Sohani, AR Hochberg, EP Bernstein, BE AF Ryan, Russell J. H. Drier, Yotam Whitton, Holly Cotton, M. Joel Kaur, Jasleen Issner, Robbyn Gillespie, Shawn Epstein, Charles B. Nardi, Valentina Sohani, Aliyah R. Hochberg, Ephraim P. Bernstein, Bradley E. TI Detection of Enhancer-Associated Rearrangements Reveals Mechanisms of Oncogene Dysregulation in B-cell Lymphoma SO CANCER DISCOVERY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; CLASSICAL HODGKIN LYMPHOMA; GENOME-WIDE ASSOCIATION; SUPER-ENHANCERS; TRANSCRIPTIONAL REGULATION; MYC TRANSLOCATIONS; RISK LOCI; DISEASE; GENE AB B-cell lymphomas frequently contain genomic rearrangements that lead to oncogene activation by heterologous distal regulatory elements. We used a novel approach called "pinpointing enhancer-associated rearrangements by chromatin immunoprecipitation," or PEAR-ChIP, to simultaneously map enhancer activity and proximal rearrangements in lymphoma cell lines and patient biopsies. This method detects rearrangements involving known cancer genes, including CCND1, BCL2, MYC, PDCD1LG2, NOTCH1, CIITA, and SGK1, as well as novel enhancer duplication events of likely oncogenic significance. We identify lymphoma subtype-specific enhancers in the MYC locus that are silenced in lymphomas with MYC-activating rearrangements and are associated with germline polymorphisms that alter lymphoma risk. We show that BCL6-locus enhancers are acetylated by the BCL6-activating transcription factor MEF2B, and can undergo genomic duplication, or target the MYC promoter for activation in the context of a "pseudo-double-hit" t(3;8)(q27;q24) rearrangement linking the BCL6 and MYC loci. Our work provides novel insights regarding enhancer-driven oncogene activation in lymphoma. SIGNIFICANCE: We demonstrate a novel approach for simultaneous detection of genomic rearrangements and enhancer activity in tumor biopsies. We identify novel mechanisms of enhancer-driven regulation of the oncogenes MYC and BCL6, and show that the BCL6 locus can serve as an enhancer donor in an "enhancer hijacking" translocation. (C) 2015 AACR. C1 [Ryan, Russell J. H.; Drier, Yotam; Cotton, M. Joel; Kaur, Jasleen; Gillespie, Shawn; Nardi, Valentina; Sohani, Aliyah R.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ryan, Russell J. H.; Drier, Yotam; Cotton, M. Joel; Kaur, Jasleen; Nardi, Valentina; Sohani, Aliyah R.; Hochberg, Ephraim P.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA USA. [Ryan, Russell J. H.; Drier, Yotam; Whitton, Holly; Cotton, M. Joel; Kaur, Jasleen; Issner, Robbyn; Gillespie, Shawn; Epstein, Charles B.; Bernstein, Bradley E.] Broad Inst Harvard Univ & MIT, Cambridge, MA USA. [Hochberg, Ephraim P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Bernstein, BE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM Bernstein.Bradley@mgh.harvard.edu RI Drier, Yotam/K-5208-2012 OI Drier, Yotam/0000-0003-1725-2995 FU NIH [T32GM007748, T32CA009216]; ENCODE; Leukemia and Lymphoma Society; Howard Hughes Medical Institute FX R.J.H. Ryan received funding from NIH training grants T32GM007748 and T32CA009216. B.E. Bernstein received funding from ENCODE, the Leukemia and Lymphoma Society, and the Howard Hughes Medical Institute. NR 51 TC 7 Z9 7 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD OCT PY 2015 VL 5 IS 10 BP 1058 EP 1071 DI 10.1158/2159-8290.CD-15-0370 PG 14 WC Oncology SC Oncology GA CX3JU UT WOS:000365595900024 PM 26229090 ER PT J AU Cheng, CW Yilmaz, OH AF Cheng, Chia-Wei Yilmaz, Oemer H. TI IGFBP3 and T1D: Systemic Factors in Colonic Stem Cell Function and Diabetic Enteropathy SO CELL STEM CELL LA English DT Editorial Material AB Patients with type 1 diabetes (T1D) often experience gastrointestinal enteropathy (DE) of unclear etiology. Now in Cell Stem Cell, D'Addio et al. (2015) utilize organoid culture models to study the roles of stem cells in DE and show that circulating IGF/IGFBP3 controls colonic stem cell function during homeostasis and in T1D patients. C1 [Cheng, Chia-Wei; Yilmaz, Oemer H.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA. [Cheng, Chia-Wei; Yilmaz, Oemer H.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Yilmaz, Oemer H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yilmaz, Oemer H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yilmaz, OH (reprint author), MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA. EM ohyilmaz@mit.edu FU NCI NIH HHS [P30 CA014051]; NIA NIH HHS [R00 AG045144] NR 6 TC 1 Z9 1 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD OCT 1 PY 2015 VL 17 IS 4 BP 379 EP 380 DI 10.1016/j.stem.2015.09.008 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA CX4TS UT WOS:000365693800004 PM 26431180 ER PT J AU Liu, X Huh, JY Gong, H Chamberland, JP Brinkoetter, MT Hamnvik, OPR Mantzoros, CS AF Liu, X. Huh, J. Y. Gong, H. Chamberland, J. P. Brinkoetter, M. T. Hamnvik, O-PR Mantzoros, C. S. TI Lack of mature lymphocytes results in obese but metabolically healthy mice when fed a high-fat diet SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID ADIPOSE-TISSUE INFLAMMATION; INSULIN-RESISTANCE; IMMUNE CELLS; BEIGE FAT; T-CELLS; WOMEN; MACROPHAGES; SENSITIVITY; HOMEOSTASIS; EXPRESSION AB BACKGROUND/OBJECTIVES: Obesity is characterized by chronic inflammation and immune dysregulation, as well as insulin resistance, but the link between obesity and adaptive immunity remains to be fully studied. METHODS: To elucidate the role of adaptive immunity on body composition, glucose homeostasis and inflammation, recombination-activating gene 1 knockout (Rag1 - / -) mice, without mature T-lymphocytes or B-lymphocytes, were maintained on a low-or high-fat diet (LFD and HFD, respectively) for 11 weeks. RESULTS: Rag1 - / - mice fed HFD gained significantly more weight and had increased body fat compared with wild type. Downregulation of energy expenditure as well as brown fat uncoupling protein UCP-1 and UCP-3 gene expression were noticed in HFD-fed Rag1 - / - mice compared with LFD. HFD mice had significantly decreased energy intake compared with LFD mice, consistent with decreased agouti-related protein and increased pro-opiomelanocortin gene expression levels in the hypothalamus. Moreover, compared with wild type, Rag1 - / - mice had lower interleukin (IL)-4 levels, a cytokine recently found to induce browning in white adipocytes, and higher IL-12 levels in HFD-fed Rag1 - / - mice. Despite that HFD Rag1 - / - mice were more obese, they had similar glucose, insulin and adiponectin levels, while leptin was marginally increased. CONCLUSIONS: Mice with deficiency in adaptive immunity are obese, partly owing to decreased energy expenditure, but are metabolically normal, suggesting that mature lymphocytes have necessary roles in the development of obesity-related metabolic dysregulation. C1 [Liu, X.; Huh, J. Y.; Gong, H.; Chamberland, J. P.; Brinkoetter, M. T.; Mantzoros, C. S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02130 USA. [Chamberland, J. P.; Hamnvik, O-PR; Mantzoros, C. S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02115 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, 330 Brookline Ave,Feldberg 875, Boston, MA 02130 USA. EM cmantzor@bidmc.harvard.edu FU Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH Award) [UL1 RR 025758]; Harvard Catalyst/The Harvard Clinical and Translational Science Center (Harvard University); Beth Israel Deaconess Medical Center; Clinical Science Research and Development Service of VA Office of Research and Development [1I01CX000422-01A1] FX This work was conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH Award no. UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health-care centers), a discretionary grant from Beth Israel Deaconess Medical Center and award number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health-care centers, the National Center for Research Resources or the National Institutes of Health. NR 34 TC 2 Z9 2 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD OCT PY 2015 VL 39 IS 10 BP 1548 EP 1557 DI 10.1038/ijo.2015.93 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CW4KR UT WOS:000364960700020 PM 25994806 ER PT J AU Jones, SF Siu, LL Bendell, JC Cleary, JM Razak, ARA Infante, JR Pandya, SS Bedard, PL Pierce, KJ Houk, B Roberts, WG Shreeve, SM Shapiro, GI AF Jones, Suzanne F. Siu, Lillian L. Bendell, Johanna C. Cleary, James M. Razak, Albiruni R. A. Infante, Jeffrey R. Pandya, Shuchi S. Bedard, Philippe L. Pierce, Kristen J. Houk, Brett Roberts, W. Gregory Shreeve, S. Martin Shapiro, Geoffrey I. TI A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Focal adhesion kinase; Proline-rich tyrosine kinase-2; Dose-escalation study; VS-6063; Defactinib ID THERAPEUTIC INTERVENTION; SIGNALING PATHWAYS; CELL-MIGRATION; FAK; CANCER; GROWTH; ANGIOGENESIS; MESOTHELIOMA; PYK2; PROGRESSION AB Objective VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2). This phase I dose-escalation study was conducted in patients with advanced solid malignancies. Methods Using a traditional 3+3 design, VS-6063 was administered orally twice daily (b.i.d.) in 21-day cycles to cohorts of three to six patients. In cycle 1, a lead-in dose was administered to assess single-dose pharmacokinetics; steady-state pharmacokinetics was assessed after 15 days of continuous dosing. Dose escalation was performed in the fasted state, and repeated in two additional cohorts in the fed state. Results Forty-six patients were treated across nine dose levels (12.5-750 mg b.i.d.). Dose-limiting toxicities, comprising headache (n=1), fatigue (n=1) and unconjugated hyperbilirubinemia (n=3), occurred at the 300- or 425-mg b.i.d. dose level and were reversible. Frequent adverse events included nausea (37 %), fatigue (33 %), vomiting (28 %), diarrhea (22 %) and headache (22 %). A maximum-tolerated dose was not defined. Dose escalation was stopped at the 750-mg b.i.d. dose due to decreased serum exposure in the 500- and 750-mg versus 300- and 425-mg groups. Food delayed the time to peak serum concentration without affecting serum drug exposure. No radiographic responses were reported. Disease stabilization at similar to 12 weeks occurred in six of 37 (16 %) patients receiving doses >= 100 mg b.i.d. Conclusions VS-6063 has an acceptable safety profile. Treatment-related adverse events were mild to moderate, and reversible. The recommended phase II fasting dose of VS-6063 is 425 mg b.i.d. C1 [Jones, Suzanne F.; Bendell, Johanna C.; Infante, Jeffrey R.] Sarah Cannon Res Inst, Nashville, TN 37203 USA. [Siu, Lillian L.; Razak, Albiruni R. A.; Bedard, Philippe L.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Cleary, James M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pandya, Shuchi S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Pierce, Kristen J.; Roberts, W. Gregory] Pfizer Oncol, Groton, CT USA. [Houk, Brett; Shreeve, S. Martin] Pfizer Oncol, La Jolla, CA USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jones, SF (reprint author), Sarah Cannon Res Inst, 250 25th Ave North,Suite 200, Nashville, TN 37203 USA. EM suzanne.jones@scresearch.net FU Pfizer Inc. FX Drs. K. Pierce, B. Houk, and W.G. Roberts are fulltime employees of Pfizer Inc. At the time the study was conducted, Dr. S.M. Shreeve was an employee of Pfizer Inc.; currently he is an employee of Janssen Pharmaceutical Companies of Johnson and Johnson. At the time the study was conducted, Dr. S. Pandya was an employee of Beth Israel Deaconess Medical Center; currently she is an employee of Acceleron Pharma. Dr. L. Siu receives research funding for clinical trial support from Pfizer Inc. NR 37 TC 9 Z9 9 U1 2 U2 6 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 OCT PY 2015 VL 33 IS 5 BP 1100 EP 1107 DI 10.1007/s10637-015-0282-y PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA CW4PD UT WOS:000364972700012 PM 26334219 ER PT J AU Tolaney, SM Tan, S Guo, H Barry, W Van Allen, E Wagle, N Brock, J Larrabee, K Paweletz, C Ivanova, E Janne, P Overmoyer, B Wright, JJ Shapiro, GI Winer, EP Krop, IE AF Tolaney, Sara M. Tan, Sally Guo, Hao Barry, William Van Allen, Eliezer Wagle, Nikhil Brock, Jane Larrabee, Katherine Paweletz, Cloud Ivanova, Elena Janne, Pasi Overmoyer, Beth Wright, John J. Shapiro, Geoffrey I. Winer, Eric P. Krop, Ian E. TI Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Triple-negative breast cancer; Tivantinib; MET; ARQ 197 ID HEPATOCYTE GROWTH-FACTOR; CELL LUNG-CANCER; MET MESSENGER-RNA; HEPATOCELLULAR-CARCINOMA; CYTOTOXIC ACTIVITY; PLACEBO; TUMORS; OVEREXPRESSION; INHIBITION; EXPRESSION AB Background MET expression and activation appear to be important for initiation and progression of triple-negative breast cancer. Tivantinib (ARQ 197) is an orally administered agent that targets MET, although recent preclinical data suggests the agent may have mechanisms of action that are independent of MET signaling. We conducted a phase 2 study of tivantinib monotherapy in patients with metastatic triple-negative breast cancer. Methods Patients with metastatic triple-negative breast cancer who had received 1 to 3 prior lines of chemotherapy in the metastatic setting were enrolled into this two-stage, single arm phase 2 study. Treatment consisted of twice daily oral dosing of tivantinib (360 mg po bid) during a 21-day cycle. Patients underwent restaging scans at 6 weeks, and then every 9 weeks. Tumor biomarkers that might predict response to tivantinib were explored. Results 22 patients were enrolled. The overall response rate was 5 % (95 % CI 0-25 %) and the 6-month progression-free survival (PFS) was 5 % (95 % CI 0-25 %), with one patient achieving a partial response (PR). Toxicity was minimal with only 5 grade >= 3 adverse events (one grade 3 anemia, one grade 3 fatigue, and 3 patients with grade 3/4 neutropenia). Conclusion This study represents the first evaluation of tivantinib for the treatment of metastatic triple-negative breast cancer. These results suggest that single agent tivantinib is well tolerated, but did not meet prespecified statistical targets for efficacy. C1 [Tolaney, Sara M.; Wagle, Nikhil; Larrabee, Katherine; Paweletz, Cloud; Ivanova, Elena; Janne, Pasi; Overmoyer, Beth; Shapiro, Geoffrey I.; Winer, Eric P.; Krop, Ian E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Tan, Sally] Harvard Univ, Sch Med, Boston, MA USA. [Guo, Hao; Barry, William] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Van Allen, Eliezer; Wagle, Nikhil] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA. [Brock, Jane] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Paweletz, Cloud; Ivanova, Elena; Janne, Pasi] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD USA. RP Tolaney, SM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Yawkey 1257, Boston, MA 02215 USA. EM stolaney@partners.org RI Guo, Hao/E-8921-2015 OI Guo, Hao/0000-0003-1658-0989 FU Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI) [NCT01575522]; Susan F. Smith Executive Council Fund FX This work was supported by the Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI) through grant number NCT01575522 as well as the Susan F. Smith Executive Council Fund. We thank Carrie Sougnez and the Broad Genomics Platform for sequencing and analysis collaborations. NR 27 TC 11 Z9 11 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 OCT PY 2015 VL 33 IS 5 BP 1108 EP 1114 DI 10.1007/s10637-015-0269-8 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA CW4PD UT WOS:000364972700013 PM 26123926 ER PT J AU Patel, V Hale, TM Palakodeti, S Kvedar, JC Jethwani, K AF Patel, Vishal Hale, Timothy M. Palakodeti, Sandeep Kvedar, Joseph C. Jethwani, Kamal TI Prescription Tablets in the Digital Age: A Cross-Sectional Study Exploring Patient and Physician Attitudes Toward the Use of Tablets for Clinic-Based Personalized Health Care Information Exchange SO JMIR RESEARCH PROTOCOLS LA English DT Article DE electronic health records; tablets; health education; self-management; primary care; physician patient relationship; digital health; iPad; patient-reported outcome measures ID ELECTRONIC MEDICAL-RECORDS; MULTIMEDIA COMPUTER; SELF-MANAGEMENT; EDUCATION; INTERVENTIONS; ENGAGEMENT; FEASIBILITY; TELEHEALTH; KNOWLEDGE; BARRIERS AB Background: To reduce the cost of health care while increasing efficiency and quality, health systems are seeking innovative means to engage and empower patients. Improved use of information technology and electronic health record (EHR) infrastructure is essential, and required for "meaningful use" as mandated by the federal government. Providing personalized health information using tablets at the point of care could enhance the clinical experience and enable efficient collection of patient reported outcome measures to guide clinical decision making. Objective: The aim of this study is to explore patient and provider attitudes and interest in a proposed clinic-based tablet system for personal health information exchange. To provide a context to understand patients' use of tablets during their clinic visit, we also examine patients' current activities and time spent in the waiting room, and their use of health information resources. Methods: Surveys were administered to 84 patients in the waiting room of a community health center affiliated with Massachusetts General Hospital (MGH) in Boston, MA. This survey included a vignette and illustration describing a proposed tablet-based system in which the patient, upon sign in at the clinic, receives a tablet loaded with personalized information tailored to their specific medical conditions and preferences. Patients were queried about their interest in such a system in comparison to traditional forms of patient education as well as their current health information seeking behaviors and activities and time spent in the waiting room. Interviews with five MGH-affiliated health care providers were conducted to assess their opinions regarding the proposed tablet system. Results: The majority (>60%) of patients were "very" or "extremely" interested in the proposed tablet system and thought it would improve their knowledge about their medical condition (60%), assist them in making healthy choices (57%), and help them to feel more comfortable talking with their provider (55%). Patients thought the system would be more motivating, informative, and engaging than traditional printed health education materials. The tablet system was not considered more effective than face-to-face interaction with providers, though 44% thought it would improve their relationship with their physician. Overall, 91% of respondents were willing to learn how to use a tablet and 75% reported being "very" or "extremely" confident they could use one. Four of the five providers believed that the proposed tablet system would improve clinical workflow and patient education. Patients and providers were concerned about privacy and security of data collected using the tablets. Conclusions: Both patients and providers were highly amenable to integrating tablets into the clinical experience, and tablets may be useful in improving patients' health knowledge, the collection of patient reported outcome measures, and improved patient-provider communication. Further research into operationalizing such systems and their validation is necessary before integration into standard clinical practice. C1 [Patel, Vishal] Kaiser Permanente, San Francisco, CA USA. [Hale, Timothy M.; Kvedar, Joseph C.; Jethwani, Kamal] Partners HealthCare Connected Hlth, Connected Hlth Innovat, Boston, MA 02114 USA. [Hale, Timothy M.; Kvedar, Joseph C.; Jethwani, Kamal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hale, Timothy M.; Kvedar, Joseph C.; Jethwani, Kamal] Harvard Univ, Sch Med, Boston, MA USA. [Palakodeti, Sandeep] Mayo Clin, Dept Hosp Internal Med, Rochester, MN USA. RP Hale, TM (reprint author), Partners HealthCare Connected Hlth, Connected Hlth Innovat, 25 New Chardon St,Suite 300, Boston, MA 02114 USA. EM tmhale@mgh.harvard.edu OI Hale, Timothy/0000-0002-4228-465X; Patel, Vishal/0000-0003-2844-2698 NR 49 TC 4 Z9 4 U1 2 U2 5 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1929-0748 J9 JMIR RES PROTOC JI JMIR RES. Protoc. PD OCT-DEC PY 2015 VL 4 IS 4 AR UNSP e116 DI 10.2196/resprot.3806 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CW5NY UT WOS:000365043900011 PM 26481906 ER PT J AU Aguayo-Mazzucato, C Dilenno, A Hollister-Lock, J Cahill, C Sharma, A Weir, G Colton, C Bonner-Weir, S AF Aguayo-Mazzucato, Cristina Dilenno, Amanda Hollister-Lock, Jennifer Cahill, Christopher Sharma, Arun Weir, Gordon Colton, Clark Bonner-Weir, Susan TI MAFA and T-3 Drive Maturation of Both Fetal Human Islets and Insulin-Producing Cells Differentiated From hESC SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PANCREATIC-BETA-CELLS; EMBRYONIC STEM-CELLS; IN-VITRO; SECRETION; PROINSULIN; EXPRESSION; ENDOCRINE; EXPOSURE; RELEASE; ADULT AB Context: Human embryonic stem cells (hESCs) differentiated toward beta-cells and fetal human pancreatic islet cells resemble each other transcriptionally and are characterized by immaturity with a lack of glucose responsiveness, low levels of insulin content, and impaired proinsulin-to-insulin processing. However, their response to stimuli that promote functionality have not been compared. Objective: The objective of the study was to evaluate the effects of our previous strategies for functional maturation developed in rodents in these two human models of beta-cell immaturity and compare their responses. Design, Settings, Participants, and Interventions: In proof-of-principle experiments using either adenoviral-mediated overexpression of V-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) or the physiologically driven path via thyroid hormone (T-3) and human fetal islet-like cluster (ICC) functional maturity was evaluated. Then the effects of T-3 were evaluated upon the functional maturation of hESCs differentiated toward beta-cells. Main Outcome Measures: Functional maturation was evaluated by the following parameters: glucose responsiveness, insulin content, expression of the mature beta-cell transcription factor MAFA, and proinsulin-to-insulin processing. Results: ICCs responded positively to MAFA overexpression and T-3 treatment as assessed by two different maturation parameters: increased insulin secretion at 16.8 mM glucose and increased proinsulin-to-insulin processing. In hESCs differentiated toward beta-cells, T-3 enhanced MAFA expression, increased insulin content (probably mediated by the increased MAFA), and increased insulin secretion at 16.8 mM glucose. Conclusion: T-3 is a useful in vitro stimulus to promote human beta-cell maturation as shown in both human fetal ICCs and differentiated hESCs. The degree of maturation induced varied in the two models, possibly due to the different developmental status at the beginning of the study. C1 [Aguayo-Mazzucato, Cristina; Hollister-Lock, Jennifer; Cahill, Christopher; Sharma, Arun; Weir, Gordon; Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Dilenno, Amanda; Colton, Clark] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU National Institutes of Health [R01 DK093909, P30 DK036836]; Juvenile Diabetes Research Foundation [1-2011-591]; Diabetes Research and Wellness Foundation FX This work was supported by National Institutes of Health Grant R01 DK093909 (to S.B.-W.), Grant P30 DK036836 for the Joslin Diabetes Research Center (to G.L.K.), and by Juvenile Diabetes Research Foundation Grant 1-2011-591 (to S.B.-W.). This work also was supported by the Diabetes Research and Wellness Foundation and an important group of private donors. NR 23 TC 7 Z9 7 U1 1 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2015 VL 100 IS 10 BP 3651 EP 3659 DI 10.1210/jc.2015-2632 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3WI UT WOS:000364922600032 PM 26207953 ER PT J AU Amlashi, FG Swearingen, B Faje, AT Nachtigall, LB Miller, KK Klibanski, A Biller, BMK Tritos, NA AF Amlashi, Fatemeh G. Swearingen, Brooke Faje, Alexander T. Nachtigall, Lisa B. Miller, Karen K. Klibanski, Anne Biller, Beverly M. K. Tritos, Nicholas A. TI Accuracy of Late-Night Salivary Cortisol in Evaluating Postoperative Remission and Recurrence in Cushing's Disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID URINARY FREE CORTISOL; TRANSSPHENOIDAL SURGERY; PITUITARY SURGERY; ENZYME-IMMUNOASSAY; DIAGNOSIS; PERFORMANCE; REPRODUCIBILITY; CURE AB Context: Late-night salivary cortisol (LNSC) is well-validated in the diagnosis of Cushing's disease (CD). The accuracy of LNSC during follow-up of patients undergoing transsphenoidal surgery (TSS) has not been fully characterized. Objectives: We examined the accuracy of LNSC in establishing remission and identifying recurrence in postoperative patients with CD. Design: This is a retrospective study. Patients: Records of patients with CD who underwent TSS by a single neurosurgeon in our tertiary center (2005-2014) were analyzed (N = 224). Patients were selected for further investigation (n = 165) if there was at least one available LNSC test obtained after TSS (either within 3 months or during long-term follow-up). Extracted data included demographic and clinical characteristics, magnetic resonance imaging and laboratory data (morning serum cortisol, 24-hour urine free cortisol [UFC], LNSC). Main Outcomes and Measures: Remission was defined as nadir morning serum cortisol less than 5 mcg/dl and nadir 24-hour UFC less than 23 mcg. Recurrence was considered definite if confirmed surgically or prompted radiotherapy. Results: Surgical remission occurred in 89% of 89 patients with available LNSC data. LNSC, obtained within 3 months of TSS, established remission with 94% sensitivity and 80% specificity at a cutpoint of 1.9 nmol/l (area under the curve [AUC] = 0.90). At a median follow-up of 53.5 months, LNSC established recurrence(75% sensitivity and 95% specificity) at a cutpoint of 7.4 nmol/l(AUC = 0.87), and 24-hour UFC established recurrence (68% sensitivity and 100% specificity) at a cutpoint of 1.6-fold above normal (AUC = 0.82). Conclusions: LNSC may accurately establish remission after TSS and identify recurrence more accurately than 24-hour UFC during long-term follow-up. C1 [Amlashi, Fatemeh G.; Faje, Alexander T.; Nachtigall, Lisa B.; Miller, Karen K.; Klibanski, Anne; Biller, Beverly M. K.; Tritos, Nicholas A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Swearingen, Brooke] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Amlashi, Fatemeh G.; Swearingen, Brooke; Faje, Alexander T.; Nachtigall, Lisa B.; Miller, Karen K.; Klibanski, Anne; Biller, Beverly M. K.; Tritos, Nicholas A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Zero Emerson Pl 112, Boston, MA 02114 USA. EM ntritos@mgh.harvard.edu FU Pfizer; Ipsen; Novo Nordisk; Cortendo; Novartis FX N.A.T. has received institution-directed research funding from Pfizer, Ipsen, and Novo Nordisk. B.M.K.B. is the principal investigator of research grants to Massachusetts General Hospital from Cortendo and Novartis and is an occasional consultant to Cortendo, HRA Pharma, and Novartis. F.G.A., B.S., A.T.F., L.B.N., K.K.M., and A.K. have no conflicts of interest to disclose. NR 33 TC 6 Z9 6 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2015 VL 100 IS 10 BP 3770 EP 3777 DI 10.1210/jc.2015-2107 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3WI UT WOS:000364922600046 PM 26196950 ER PT J AU Mather, KJ Kim, C Christophi, CA Aroda, VR Knowler, WC Edelstein, SE Florez, JC Labrie, F Kahn, SE Goldberg, RB Barrett-Connor, E AF Mather, K. J. Kim, C. Christophi, C. A. Aroda, V. R. Knowler, W. C. Edelstein, S. E. Florez, J. C. Labrie, F. Kahn, S. E. Goldberg, R. B. Barrett-Connor, E. CA Diabet Prevention Program TI Steroid Sex Hormones, Sex Hormone-Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPAIRED FASTING GLUCOSE; LIFE-STYLE INTERVENTION; POSTMENOPAUSAL WOMEN; TOTAL TESTOSTERONE; METABOLIC SYNDROME; MEN; RISK; METFORMIN; MELLITUS; HEALTH AB Context: Steroid sex hormones and SHBG may modify metabolism and diabetes risk, with implications for sex-specific diabetes risk and effects of prevention interventions. Objective: This study aimed to evaluate the relationships of steroid sex hormones, SHBG and SHBG single-nucleotide polymorphisms (SNPs) with diabetes risk factors and with progression to diabetes in the Diabetes Prevention Program (DPP). Design and Setting: This was a secondary analysis of a multicenter randomized clinical trial involving 27 U.S. academic institutions. Participants: The study included 2898 DPP participants: 969 men, 948 premenopausal women not taking exogenous sex hormones, 550 postmenopausal women not taking exogenous sex hormones, and 431 postmenopausal women taking exogenous sex hormones. Interventions: Participants were randomized to receive intensive lifestyle intervention, metformin, or placebo. Main Outcomes: Associations of steroid sex hormones, SHBG, and SHBG SNPs with glycemia and diabetes risk factors, and with incident diabetes over median 3.0 years (maximum, 5.0 y). Results: T and DHT were inversely associated with fasting glucose in men, and estrone sulfate was directly associated with 2-hour post-challenge glucose in men and premenopausal women. SHBG was associated with fasting glucose in premenopausal women not taking exogenous sex hormones, and in postmenopausal women taking exogenous sex hormones, but not in the other groups. Diabetes incidence was directly associated with estrone and estradiol and inversely with T in men; the association with T was lost after adjustment for waist circumference. Sex steroids were not associated with diabetes outcomes in women. SHBG and SHBG SNPs did not predict incident diabetes in the DPP population. Conclusions: Estrogens and T predicted diabetes risk in men but not in women. SHBG and its polymorphisms did not predict risk in men or women. Diabetes risk is more potently determined by obesity and glycemia than by sex hormones. C1 [Mather, K. J.] Indiana Univ, Dept Med, Indianapolis, IN 46202 USA. [Kim, C.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Kim, C.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Christophi, C. A.; Edelstein, S. E.] George Washington Univ, Biostat Ctr, Rockville, MD 20850 USA. [Aroda, V. R.] Medstar Hlth Res Inst, Hyattsville, MD 20782 USA. [Knowler, W. C.] NIDDK, Phoenix, AZ 85014 USA. [Florez, J. C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, J. C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Florez, J. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Labrie, F.] Endoceutics Inc, Quebec City, PQ G1W 2J5, Canada. [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Kahn, S. E.] Univ Washington, Seattle, WA 98108 USA. [Goldberg, R. B.] Univ Miami, Miami, FL 33124 USA. [Barrett-Connor, E.] Univ Calif San Diego, San Diego, CA 92093 USA. RP Mather, KJ (reprint author), George Washington Univ, Care Diabet Prevent Program Coordinating Ctr, Biostat Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20850 USA. EM dppmail@bsc.gwu.edu OI Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health/National Institute of Diabetes, Digestive and Kidney Disorders; National Institute of Child Health and Human Development; National Institute of Aging; Office of Research in Minority Health and Health Disparities; Office of Research in Womens' Health Indian Health Service; Centers for Disease Control Clinical Genetics Research Program; National Center for Research Resources; American Diabetes Association; Bristol-Meyers Squibb; Lipha; Parke-Davis [R01 DK072041] FX This work was supported by National Institutes of Health/National Institute of Diabetes, Digestive and Kidney Disorders, National Institute of Child Health and Human Development, National Institute of Aging, Office of Research in Minority Health and Health Disparities, Office of Research in Womens' Health Indian Health Service, Centers for Disease Control Clinical Genetics Research Program, National Center for Research Resources, American Diabetes Association, Bristol-Meyers Squibb, Lipha, Parke-Davis, R01 DK072041. NR 35 TC 10 Z9 10 U1 3 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2015 VL 100 IS 10 BP 3778 EP 3786 DI 10.1210/jc.2015-2328 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3WI UT WOS:000364922600047 PM 26200237 ER PT J AU Guo, FJ Garvey, WT AF Guo, Fangjian Garvey, W. Timothy TI Development of a Weighted Cardiometabolic Disease Staging (CMDS) System for the Prediction of Future Diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; TREATMENT PANEL-III; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK; INSULIN-RESISTANCE; AFRICAN-AMERICANS; CLINICAL ENDOCRINOLOGISTS; POSITION STATEMENT; METABOLIC SYNDROME; PHYSICAL-ACTIVITY AB Context: Metabolic syndrome traits are important risk factors for diabetes; however, each trait has different predictive power for future diabetes. Additionally, the impact of insulin resistance on metabolic profile can differ by gender and racial group, suggesting that gender-race specific prediction algorithms for diabetes may be warranted. Objective: To develop a quantitative scoring system based on weighting of risk components in the cardiometabolic disease staging (CMDS) system for the prediction of future diabetes. Design, Setting, and Participants: We derived the CMDS score in 2857 participants with valid follow-up information on incident diabetes from the Coronary Artery Risk Development in Young Adults study and validated it in 6425 older participants from the Atherosclerosis Risk in Communities study. We assigned a simple integer value for each CMDS risk factor component. Main Outcome Measures: Incident diabetes. Results: Fasting glucose, 2-hour glucose, waist circumference, and blood pressure components contributed similarly for the prediction of future diabetes (CMDS scores, 23, 21, 26, and 20, respectively). The area under the receiver operating characteristic curve was 0.7158 for the CMDS scoring system, whereas it was 0.7053 for the Framingham diabetes score. The CMDS components performed differently for prediction of future diabetes in Black and White men and women. The components with the highest predictive power for diabetes were waist circumference in Black men, 2-hour glucose in Black women, and fasting glucose in both White men and White women. Conclusions: The weighted CMDS score has high model discrimination power for diabetes and can be used clinically to identify patients for weight loss therapy based on differential risk for future diabetes. C1 [Guo, Fangjian] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. [Guo, Fangjian] Univ Texas Med Branch, Ctr Interdisciplinary Res Womens Hlth, Galveston, TX 77555 USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35233 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Guo, FJ (reprint author), Univ Texas Med Branch, Dept Obstet & Gynecol, 301 Univ Blvd, Galveston, TX 77555 USA. EM faguo@utmb.edu; garveyt@uab.edu OI Guo, Fangjian/0000-0003-3729-2724 FU Department of Veterans Affairs; University of Alabama at Birmingham Diabetes Research Center [P60-DK079626]; Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) at the NIH [T32HD055163]; National Institutes of Health (NIH) [DK-038765, DK-083562] FX This study was partly supported by the Merit Review program of the Department of Veterans Affairs, the National Institutes of Health (NIH) (Grants DK-038765 and DK-083562), and the University of Alabama at Birmingham Diabetes Research Center (Grant P60-DK079626). F.G. is currently supported by an institutional training grant (National Research Service Award T32HD055163) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) at the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or the NIH. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. NR 36 TC 2 Z9 3 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2015 VL 100 IS 10 BP 3871 EP 3877 DI 10.1210/jc.2015-2691 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3WI UT WOS:000364922600058 PM 26241327 ER PT J AU Choi, JH Balasubramanian, R Lee, PH Shaw, ND Hall, JE Plummer, L Buck, CL Kottler, ML Jarzabek, K Wolczynski, S Quinton, R Latronico, AC Dode, C Ogata, T Kim, HG Layman, LC Gusella, JF Crowley, WF AF Choi, Jin-Ho Balasubramanian, Ravikumar Lee, Phil H. Shaw, Natalie D. Hall, Janet E. Plummer, Lacey Buck, Cassandra L. Kottler, Marie-Laure Jarzabek, Katarzyna Wolczynski, Slawomir Quinton, Richard Latronico, Ana Claudia Dode, Catherine Ogata, Tsutomu Kim, Hyung-Goo Layman, Lawrence C. Gusella, James F. Crowley, William F., Jr. TI Expanding the Spectrum of Founder Mutations Causing Isolated Gonadotropin-Releasing Hormone Deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HYPOGONADOTROPIC HYPOGONADISM; LINKAGE-DISEQUILIBRIUM; HUMAN GENOME; RECEPTOR; GENE; AGE AB Context: Loss of function (LoF) mutations in more than 20 genes are now known to cause isolated GnRH deficiency (IGD) in humans. Most causal IGD mutations are typically private, ie, limited to a single individual/pedigree. However, somewhat paradoxically, four IGD genes (GNRH1, TAC3, PROKR2, and GNRHR) have been shown to harbor LoF founder mutations that are shared by multiple unrelated individuals. It is not known whether similar founder mutations occur in other IGD genes. Objective: The objective of the study was to determine whether shared deleterious mutations in IGD-associated genes represent founder alleles. Setting: This study was an international collaboration among academic medical centers. Methods: IGD patients with shared mutations, defined as those documented in three or more unrelated probands in 14 IGD-associated genes, were identified from various academic institutions, the Human Gene Mutation Database, and literature reports by other international investigators. Haplotypes of single-nucleotide polymorphisms and short tandem repeats surrounding the mutations were constructed to assess genetic ancestry. Results: A total of eight founder mutations in five genes, GNRHR (Q106R, R262Q, R139H), TACR3 (W275X), PROKR2 (R85H), FGFR1 (R250Q, G687R), and HS6ST1 (R382W) were identified. Most founder alleles were present at low frequency in the general population. The estimated age of these mutant alleles ranged from 1925 to 5600 years and corresponded to the time of rapid human population expansion. Conclusions: We have expanded the spectrum of founder alleles associated with IGD to a total of eight founder mutations. In contrast to the approximately 9000-year-old PROKR2 founder allele that may confer a heterozygote advantage, the rest of the founder alleles are relatively more recent in origin, in keeping with the timing of recent human population expansion and any selective heterozygote advantage of these alleles requires further evaluation. C1 [Choi, Jin-Ho; Balasubramanian, Ravikumar; Shaw, Natalie D.; Hall, Janet E.; Plummer, Lacey; Buck, Cassandra L.; Crowley, William F., Jr.] Harvard Univ, Sch Med, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Choi, Jin-Ho; Balasubramanian, Ravikumar; Shaw, Natalie D.; Hall, Janet E.; Plummer, Lacey; Buck, Cassandra L.; Crowley, William F., Jr.] Harvard Univ, Sch Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Lee, Phil H.] Harvard Univ, Sch Med, Dept Med Psychiat & Neurodev, Genet Unit, Boston, MA 02114 USA. [Gusella, James F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Analyt & Translat Genet Unit,Ctr Human Genet Res, Boston, MA 02114 USA. [Gusella, James F.] Harvard Univ, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Kottler, Marie-Laure] Univ Hosp, Dept Genet, F-14003 Caen, France. [Jarzabek, Katarzyna] Polish Acad Sci, Dept Biol & Pathol Human Reprod Bialystok, Inst Anim Reprod & Food Res, Olsztyn, Poland. [Wolczynski, Slawomir] Med Univ Bialystok, Dept Reprod & Gynecol Endocrinol, PL-15276 Bialystok, Poland. [Quinton, Richard] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Latronico, Ana Claudia] Univ Sao Paulo, Fac Med, Hosp Clin, Disciplina Endocrinol, BR-05403900 Sao Paulo, Brazil. [Dode, Catherine] Univ Paris 05, AP HP, Lab Biochim & Genet Mol, Hop Cochin, F-75014 Paris, France. [Ogata, Tsutomu] Hamamatsu Univ Sch Med, Dept Mol Endocrinol, Hamamatsu, Shizuoka 4313192, Japan. [Ogata, Tsutomu] Hamamatsu Univ Sch Med, Dept Pediat, Hamamatsu, Shizuoka 4313192, Japan. [Kim, Hyung-Goo; Layman, Lawrence C.] Georgia Regents Univ, Med Coll Georgia, Sect Reprod Endocrinol Infertil & Genet, Dept Obstet & Gynecol, Augusta, GA 30912 USA. [Kim, Hyung-Goo; Layman, Lawrence C.] Georgia Regents Univ, Med Coll Georgia, Sect Reprod Endocrinol Infertil & Genet, Dept Neurosci & Regenerat Med, Augusta, GA 30912 USA. [Choi, Jin-Ho] Univ Ulsan, Coll Med, Asan Med Ctr Childrens Hosp, Dept Pediat, Seoul 138736, South Korea. RP Crowley, WF (reprint author), Harvard Univ, Sch Med, Bartlett Hall Extens 511,Fruit St, Boston, MA 02114 USA. EM wcrowley@partners.org OI Shaw, Natalie/0000-0002-0847-9170; Hall, Janet/0000-0003-4644-3061 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health Grants [R01 HD15788, U54 HD028138, HD33004]; K23 Career Development award from National Institute of Child Health and Human Development [K23 HDHD077043] FX This work was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health Grants R01 HD15788 and U54 HD028138 (to W.F.C.), and HD33004 (to L.C.L.). R.B. is supported by a K23 Career Development award from National Institute of Child Health and Human Development (K23 HDHD077043). NR 28 TC 2 Z9 2 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2015 VL 100 IS 10 BP E1378 EP E1385 DI 10.1210/jc.2015-2262 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3WI UT WOS:000364922600023 PM 26207952 ER PT J AU Sood, A Penna, FJ Eleswarapu, S Pucheril, D Weaver, J Abd-El-Barr, AER Wagner, JC Lakshmanan, Y Menon, M Trinh, QD Sammon, JD Elder, JS AF Sood, Akshay Penna, Frank J. Eleswarapu, Sriram Pucheril, Dan Weaver, John Abd-El-Barr, Abd-El-Rahman Wagner, Jordan C. Lakshmanan, Yegappan Menon, Mani Trinh, Quoc-Dien Sammon, Jesse D. Elder, Jack S. TI Incidence, admission rates, and economic burden of pediatric emergency department visits for urinary tract infection: Data from the nationwide emergency department sample, 2006 to 2011 SO JOURNAL OF PEDIATRIC UROLOGY LA English DT Article DE Pediatrics; Urinary tract infections; Temporal trends; Emergency department ID FEBRILE INFANTS; VESICOURETERAL REFLUX; UNITED-STATES; CHILDREN; MANAGEMENT; CHILDHOOD; PRIAPISM; RISK; HYPERTENSION; DIAGNOSIS AB Background The Emergency Department (ED) is being increasingly utilized as a pathway for management of acute conditions such as the urinary tract infections (UTIs). Objective We sought to assess the contemporary trends in pediatric UTI associated ED visits, subsequent hospitalization, and corresponding financial expenditure, using a large nationally representative pediatric cohort. Further, we describe the predictors of admission following a UTI associated ED visit. Methods The Nationwide Emergency Department Sample (NEDS; 2006-2011) was queried to assess temporal-trends in pediatric (age <= 17 years) ED visits for a primary diagnosis of UTI (ICD9 CM code 590. X, 595.0, and 599.0), subsequent hospital admission, and total charges. These trends were examined using the estimated annual percent change (EAPC) method. Multivariable regression models fitted with generalized estimating equations (GEE) identified the predictors of hospital admission. Results Of the 1,904,379 children presenting to the ED for management of UTI, 86 042 (4.7%) underwent hospital admission. Female ED visits accounted for almost 90% of visits and increased significantly (EAPC 3.28%; p = 0.003) from 709 visits per 100 000 in 2006 to 844 visits per 100 000 in 2011. Male UTI incidence remained unchanged over the study-period (p = 0.292). The overall UTI associated ED visits also increased significantly during the study-period (EAPC 3.14%; p = 0.006) because of the increase in female UTI associated ED visits. Overall hospital admissions declined significantly over the study-period (EAPC -5.59%; p = 0.021). Total associated charges increased significantly at an annual rate of 18.26%, increasing from 254 million USD in 2006 to 464 million USD in 2011 (p < 0.001; Figure). This increase in expenditure was likely driven by increased utilization of diagnostic CT scanning in these patients (EAPC 22.86%; p < 0.001). Ultrasonography (p = 0.805), X-ray (p = 0.196), and urine analysis/culture use (p = 0.121) did not change over the study-period. In multivariable analysis, the independent predictors of admission included younger age (p < 0.001), male gender (ORZ2.05, p < 0.001), higher comorbidity status (OR = 14.81, p < 0.001), pyelonephritis (OR = 4.45, p < 0.001) and concurrent hydronephrosis (OR = 49.42, p < 0.001), stone disease (OR = 6.44, p < 0.001), or sepsis (OR = 18.83, p < 0.001). Discussion We show that the incidence of ED visits for pediatric UTI is on the rise. This rise in incidence could be due to several factors, including increasing prevalence of metabolic conditions such as obesity, diabetes and metabolic syndrome in children predisposing them to infections, or could be secondary to increasing sexual activity amongst adolescents and changing patterns of contraceptive use (increased use of OCP in place of condoms), or more simply might just be a reflection of changing practice patterns. Second, we demonstrate that total charges for management of UTI in the ED setting are increasing rapidly; the increase is primarily driven by increasing utilization of diagnostic imaging in the ED setting, as has been demonstrated in other ED based studies as well. Conclusions In children presenting to the ED with a primary diagnosis of UTI, total ED charges are increasing at an alarming rate not commensurate with the increase in overall ED visits. While the preponderance of children presenting to the ED for UTI are treated and discharged, 4.7% of patients were admitted to the hospital for further management. The strongest predictors of inpatient admission were pyelonephritis, younger age, male gender, higher comorbidity status, and concurrent hydronephrosis, stone disease, or sepsis. Managing these at-risk patients more aggressively in the outpatient setting may prevent unnecessary ED visits and subsequent hospitalizations, and reduce associated healthcare costs. C1 [Sood, Akshay; Penna, Frank J.; Eleswarapu, Sriram; Pucheril, Dan; Weaver, John; Abd-El-Barr, Abd-El-Rahman; Menon, Mani; Trinh, Quoc-Dien; Sammon, Jesse D.; Elder, Jack S.] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat VCORE, Detroit, MI USA. [Wagner, Jordan C.] Cambridge Hlth Alliance, Dept Emergency Med, Cambridge, MA USA. [Lakshmanan, Yegappan; Elder, Jack S.] Childrens Hosp Michigan, Dept Urol, Detroit, MI 48201 USA. [Sood, Akshay; Trinh, Quoc-Dien] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg,Div Urol,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Sood, A (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM asood1@hfhs.org NR 34 TC 0 Z9 0 U1 4 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1477-5131 EI 1873-4898 J9 J PEDIATR UROL JI J. Pediatr. Urol PD OCT PY 2015 VL 11 IS 5 AR UNSP 246.e1 DI 10.1016/j.jpurol.2014.10.005 PG 8 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA CW7KJ UT WOS:000365177200004 PM 26005017 ER PT J AU Sayer, NA Noorbaloochi, S Frazier, PA Pennebaker, JW Orazem, RJ Schnurr, PP Murdoch, M Carlson, KF Gravely, A Litz, BT AF Sayer, Nina A. Noorbaloochi, Siamak Frazier, Patricia A. Pennebaker, James W. Orazem, Robert J. Schnurr, Paula P. Murdoch, Maureen Carlson, Kathleen F. Gravely, Amy Litz, Brett T. TI Randomized Controlled Trial of Online Expressive Writing to Address Readjustment Difficulties Among US Afghanistan and Iraq War Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID EMOTIONAL EXPRESSION; MEDICAL-CARE; MILITARY; DISCLOSURE; MODERATORS; CHECKLIST; SYMPTOMS; SCREEN; COMBAT; COHORT AB We examined the efficacy of a brief, accessible, nonstigmatizing online intervention-writing expressively about transitioning to civilian life. U.S. Afghanistan and Iraq war veterans with self-reported reintegration difficulty (N = 1,292, 39.3% female, M = 36.87, SD = 9.78 years) were randomly assigned to expressive writing (n = 508), factual control writing (n = 507), or no writing (n = 277). Using intention to treat, generalized linear mixed models demonstrated that 6-months postintervention, veterans who wrote expressively experienced greater reductions in physical complaints, anger, and distress compared with veterans who wrote factually (ds = 0.13 to 0.20; ps < .05) and greater reductions in PTSD symptoms, distress, anger, physical complaints, and reintegration difficulty compared with veterans who did not write at all (ds = 0.22 to 0.35; ps <= .001). Veterans who wrote expressively also experienced greater improvement in social support compared to those who did not write (d = 0.17). Relative to both control conditions, expressive writing did not lead to improved life satisfaction. Secondary analyses also found beneficial effects of expressive writing on clinically significant distress, PTSD screening, and employment status. Online expressive writing holds promise for improving health and functioning among veterans experiencing reintegration difficulty, albeit with small effect sizes. C1 [Sayer, Nina A.; Noorbaloochi, Siamak; Orazem, Robert J.; Murdoch, Maureen; Gravely, Amy] Minneapolis VA Healthcare Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Sayer, Nina A.; Noorbaloochi, Siamak; Murdoch, Maureen] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Sayer, Nina A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Frazier, Patricia A.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Pennebaker, James W.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Schnurr, Paula P.] Natl Ctr PTSD, White River Jct, VT USA. [Schnurr, Paula P.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Murdoch, Maureen] Minneapolis VA Healthcare Syst, Gen Internal Med Sect, Minneapolis, MN 55417 USA. [Carlson, Kathleen F.] VA Portland Healthcare Syst, Ctr Improve Vet Involvement Care, Portland, OR USA. [Carlson, Kathleen F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA. [Litz, Brett T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Sayer, NA (reprint author), Minneapolis VA Healthcare Syst, Ctr Chron Dis Outcomes Res, One Vet Dr, Minneapolis, MN 55417 USA. EM nina.sayer@va.gov RI Sayer, Nina/E-3249-2016 FU Department of Veterans Affairs (VA), Health Services Research and Development (HSRD) Service [DHI-07-150]; Department of Defense (DoD) [08-2-0045]; VA HSRD [CDA 08-025] FX This research was supported by the Department of Veterans Affairs (VA), Health Services Research and Development (HSR&D) Service (grant no. DHI-07-150) and the Department of Defense (DoD) (grant no. 08-2-0045). The sponsors were not involved in any aspect of the study's design and conduct; data collection, management, analysis, or interpretation of data; or in the preparation, review or approval of the manuscript. The findings and conclusions presented in this manuscript are those of the authors and do not necessarily represent the views of the VA, HSR&D, or DoD. Dr. Carlson's effort was supported by a Career Development Award from VA HSR&D (CDA 08-025) NR 35 TC 2 Z9 2 U1 4 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2015 VL 28 IS 5 BP 381 EP 390 DI 10.1002/jts.22047 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX0KL UT WOS:000365385200001 PM 26467326 ER PT J AU Goetter, EM Bui, E Ojserkis, RA Zakarian, RJ Brendel, RW Simon, NM AF Goetter, Elizabeth M. Bui, Eric Ojserkis, Rebecca A. Zakarian, Rebecca J. Brendel, Rebecca Weintraub Simon, Naomi M. TI A Systematic Review of Dropout From Psychotherapy for Posttraumatic Stress Disorder Among Iraq and Afghanistan Combat Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Review ID COGNITIVE PROCESSING THERAPY; PROLONGED EXPOSURE THERAPY; MENTAL-HEALTH TREATMENT; OEF/OIF VETERANS; VIETNAM VETERANS; SERVICE MEMBERS; WAR VETERANS; PTSD; CARE; INTERVENTION AB A significant number of veterans of the conflicts in Iraq and Afghanistan have posttraumatic stress disorder (PTSD), yet underutilization of mental health treatment remains a significant problem. The purpose of this review was to summarize rates of dropout from outpatient, psychosocial PTSD interventions provided to U.S. Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF), and Operation New Dawn (OND) veterans with combat-related PTSD. There were 788 articles that were identified which yielded 20 studies involving 1,191 individuals eligible for the review. The dropout rates in individual studies ranged from 5.0% to 78.2%, and the overall pooled dropout rate was 36%, 95% CI [26.20, 43.90]. The dropout rate differed marginally by study type (routine clinical care settings had higher dropout rates than clinical trials) and treatment format (group treatment had higher dropout rates than individual treatment), but not by whether comorbid substance dependence was excluded, by treatment modality (telemedicine vs. in-person treatment), or treatment type (exposure therapy vs. nonexposure therapy). Dropout is a critical aspect of the problem of underutilization of care among OEF/OIF/OND veterans with combat-related PTSD. Innovative strategies to enhance treatment retention are needed. C1 [Goetter, Elizabeth M.; Bui, Eric; Ojserkis, Rebecca A.; Zakarian, Rebecca J.; Brendel, Rebecca Weintraub; Simon, Naomi M.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Goetter, EM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM egoetter@mgh.harvard.edu RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 48 TC 9 Z9 9 U1 3 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2015 VL 28 IS 5 BP 401 EP 409 DI 10.1002/jts.22038 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX0KL UT WOS:000365385200003 PM 26375387 ER PT J AU Doron-LaMarca, S Niles, BL King, DW King, LA Kaiser, AP Lyons, MJ AF Doron-LaMarca, Susan Niles, Barbara L. King, Daniel W. King, Lynda A. Kaiser, Anica Pless Lyons, Michael J. TI Temporal Associations Among Chronic PTSD Symptoms in US Combat Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS; RANDOMIZED CONTROLLED-TRIAL; VIETNAM VETERANS; PSYCHOMETRIC PROPERTIES; PSYCHOLOGICAL DISTRESS; MENTAL-HEALTH; WAR VETERANS; GULF-WAR; TRAUMA AB The present study examined fluctuation over time in symptoms of posttraumatic stress disorder (PTSD) among 34 combat veterans (28 with diagnosed PTSD, 6 with subclinical symptoms) assessed every 2 weeks for up to 2 years (range of assessments = 1352). Temporal relationships were examined among four PTSD symptom clusters (reexperiencing, avoidance, emotional numbing, and hyperarousal) with particular attention to the influence of hyperarousal. Multilevel cross-lagged random coefficients autoregression for intensive time series data analyses were used to model symptom fluctuation decades after combat experiences. As anticipated, hyperarousal predicted subsequent fluctuations in the 3 other PTSD symptom clusters (reexperiencing, avoidance, emotional numbing) at subsequent 2-week intervals (rs = .45, .36, and .40, respectively). Additionally, emotional numbing influenced later reexperiencing and avoidance, and reexperiencing influenced later hyperarousal (rs = .44, .40, and .34, respectively). These findings underscore the important influence of hyperarousal. Furthermore, results indicate a bidirectional relationship between hyperarousal and reexperiencing as well as a possible chaining of symptoms (hyperarousal -> emotional numbing -> reexperiencing -> hyperarousal) and establish potential internal, intrapersonal mechanisms for the maintenance of persistent PTSD symptoms. Results suggested that clinical interventions targeting hyperarousal and emotional numbing symptoms may hold promise for PTSD of long duration. C1 [Doron-LaMarca, Susan; Niles, Barbara L.; Kaiser, Anica Pless] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. [Doron-LaMarca, Susan; Niles, Barbara L.; Kaiser, Anica Pless] Boston Univ, Sch Med, Boston, MA 02118 USA. [King, Daniel W.; King, Lynda A.] Boston Univ, Dept Psychol, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02215 USA. [King, Daniel W.; King, Lynda A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Lyons, Michael J.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. RP Niles, BL (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, 116B-2,150 South Huntington Ave, Boston, MA 02130 USA. EM Barbara.niles@va.gov FU Department of Veterans Affairs CSRD grant; Department of Veterans Affairs Merit Review grant; National Institute of Mental Health [R03MH77907, R01MH68626]; National Center for Posttraumatic Stress Disorder Behavioral Science Division FX This study was supported by Department of Veterans Affairs CSR&D grant (Susan Doron-LaMarca, Principal Investigator) and Department of Veterans Affairs Merit Review grant (Barbara L. Niles, Principal Investigator), and by National Institute of Mental Health grants R03MH77907 (Susan Doron-LaMarca, Principal Investigator), and R01MH68626 (Daniel W. King, Principal Investigator), and by funding from the National Center for Posttraumatic Stress Disorder Behavioral Science Division. The contents do not represent the views of the U.S. Department of Veteran Affairs or the United States Government. The authors gratefully acknowledge the advice on analytic method offered by Ted Walls and John Nesselroade. Finally, we wish to thank the military veterans who participated in this research for their generous contributions. NR 63 TC 1 Z9 1 U1 8 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2015 VL 28 IS 5 BP 410 EP 417 DI 10.1002/jts.22039 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX0KL UT WOS:000365385200004 PM 26367017 ER PT J AU Kachadourian, LK Smith, BN Taft, CT Vogt, D AF Kachadourian, Lorig K. Smith, Brian N. Taft, Casey T. Vogt, Dawne TI The Impact of Infidelity on Combat-Exposed Service Members SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; EXTRAMARITAL AFFAIRS; PROMOTING RECOVERY; VIETNAM VETERANS; RISK-FACTORS; SELF; DEPRESSION; INTERVENTION; CONSERVATION; PSYCHOLOGY AB This study examined relationships between combat-exposed Operation Enduring Freedom/Operation Iraqi Freedom veterans' experiences related to infidelity during deployment (i.e., indicating that a partner was unfaithful or reporting concern about potential infidelity) and postdeployment mental health, as well as the role of subsequent stress exposure and social support in these associations. The sample consisted of 571 individuals (338 men). There were 128 participants (22.2%) who indicated that their partners were unfaithful during their most recent deployment. Of the remaining 443 participants, 168 (37.8%) indicated that they were concerned that their partners might have been unfaithful. Individuals who indicated that their partners were unfaithful exhibited higher levels of posttraumatic stress symptomatology (beta = .08; f(2) = .18) and depression symptom severity (beta = .09; f(2) = .14), compared to individuals who did not indicate that their partners were unfaithful. For both men and women, reported infidelity was associated with mental health indirectly via postdeployment life stressors, whereas infidelity concerns were indirectly associated with mental health via postdeployment life stressors for men only. Findings suggested that infidelity can have a significant impact on combat-exposed veterans' mental health and highlight the need for additional research on this understudied topic within the military population. C1 [Kachadourian, Lorig K.] VA Connecticut Healthcare Syst, Natl Ctr PTSD, West Haven, CT 06516 USA. [Kachadourian, Lorig K.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Smith, Brian N.; Taft, Casey T.; Vogt, Dawne] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Smith, Brian N.; Taft, Casey T.; Vogt, Dawne] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Kachadourian, LK (reprint author), VA Connecticut Healthcare Syst, Natl Ctr PTSD, Clin Neurosci Div, 116B-2,950 Campbell Ave, West Haven, CT 06516 USA. EM lorig.kachadourian@va.gov FU Department of Veterans Affairs, Health Services Research and Development Service grant [DHI 09-086] FX This study was supported by a Department of Veterans Affairs, Health Services Research and Development Service grant ("Validation of Modified DRRI Scales in a National Sample of OEF/OIF Veterans,"Project # DHI 09-086, Dawne Vogt, Principal Investigator). NR 42 TC 0 Z9 0 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2015 VL 28 IS 5 BP 418 EP 425 DI 10.1002/jts.22033 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX0KL UT WOS:000365385200005 PM 26397362 ER PT J AU Miles, SR Smith, TL Maieritsch, KP Ahearn, EP AF Miles, Shannon R. Smith, Tracey L. Maieritsch, Kelly P. Ahearn, Eileen P. TI Fear of Losing Emotional Control Is Associated With Cognitive Processing Therapy Outcomes in US Veterans of Afghanistan and Iraq SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PTSD; SCALE; CARE AB Evidence-based treatments for posttraumatic stress disorder (PTSD) can reduce symptoms and improve veterans' psychological health. Unfortunately, many veterans leave treatment before receiving maximum benefit. Fear of emotions is related to severity of PTSD, and changes in fear of emotions are correlated with changes in PTSD symptoms. This study built upon the literature linking greater fear of emotions to PTSD severity by examining whether pretreatment fear of emotions, measured by the Affect Control Scale, was associated with completion of cognitive processing therapy (CPT) and severity of posttreatment PTSD in a sample of 89 U.S. veterans who had served in Afghanistan and Iraq. About 60% of veterans completed 10 or more therapy sessions. A logistic regression on 51 of the 89 subjects that more fear of anxiety at pretreatment was associated with decreased likelihood of completing treatment, OR = 0.93, 95% CI [0.87, 1.00]. Of those veterans who completed treatment, higher fear of anger at pretreatment was negatively related to severity of PTSD posttreatment (beta = -.29, p = .037), in a model with the other predictors. Assessing veterans for fear of anxiety and anger before CPT and teaching emotion regulation skills to those in need may reduce treatment dropout. C1 [Miles, Shannon R.] Michael E DeBakey Vet Affairs VA Med Ctr, Mental Hlth Care Line, Houston, TX USA. [Miles, Shannon R.; Smith, Tracey L.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Miles, Shannon R.] South Cent Mental Illness Res Educ & Clin Ctr MIR, Houston, TX USA. [Maieritsch, Kelly P.] Edward Hines Jr VA Hosp, Mental Hlth Serv Line, Hines, IL USA. [Ahearn, Eileen P.] Univ Wisconsin Hosp & Clin, Dept Psychiat, Madison, WI 53792 USA. [Smith, Tracey L.; Ahearn, Eileen P.] William S Middleton Mem Vet Adm Med Ctr, Mental Hlth Serv Line, Madison, WI USA. RP Miles, SR (reprint author), Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM shannon.reynolds@utulsa.edu RI Smith, Tracey/J-2030-2014 OI Smith, Tracey/0000-0001-5338-9142 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Houston VA HSR&D Center for Innovations in Quality, Effectiveness Safety [IQUEST: CIN13-413]; South Central Mental Illness Research, Education, and Clinical Center (MIRECC); U.S. Army Medical Research Acquisition Activity (USAMRAA) [W81XWH-08-2-0130] FX This material is based upon work supported (or supported in part) by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Houston VA HSR&D Center for Innovations in Quality, Effectiveness & Safety (IQUEST: CIN13-413), South Central Mental Illness Research, Education, and Clinical Center (MIRECC), and U.S. Army Medical Research Acquisition Activity (USAMRAA; W81XWH-08-2-0130; ClinicalTrials.gov Identifier: NCT00941629). The funding sources had no role in the study design; in the collection, analysis, or interpretation of the data; in the writing of the manuscript; or in the decision to submit the paper for publication. The views expressed in this article are those of the authors and do not necessarily reflect the views, position, or policy of the Department of Veterans Affairs, IQUEST, the South Central MIRECC, the U.S. Department of Defense. NR 15 TC 2 Z9 2 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2015 VL 28 IS 5 BP 475 EP 479 DI 10.1002/jts.22036 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX0KL UT WOS:000365385200014 PM 26397721 ER PT J AU Price, M Kuhn, E Hoffman, JE Ruzek, J Acierno, R AF Price, Matthew Kuhn, Eric Hoffman, Julia E. Ruzek, Josef Acierno, Ron TI Comparison of the PTSD Checklist (PCL) Administered via a Mobile Device Relative to a Paper Form SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID PSYCHOMETRIC-PROPERTIES; COMPUTER; EQUIVALENCE; TECHNOLOGY; TELEHEALTH; VETERANS AB Mobile devices are increasingly used to administer self-report measures of mental health symptoms. There are significant differences, however, in the way that information is presented on mobile devices compared to the traditional paper forms that were used to administer such measures. Such differences may systematically alter responses. The present study evaluated if and how responses differed for a self-report measure, the PTSD Checklist (PCL), administered via mobile device relative to paper and pencil. Participants were 153 trauma-exposed individuals who completed counterbalanced administrations of the PCL on a mobile device and on paper. PCL total scores (d = 0.07) and item responses did not meaningfully or significantly differ across administrations. Power was sufficient to detect a difference in total score between administrations determined by prior work of 3.46 with a d = 0.23. The magnitude of differences between administration formats was unrelated to prior use of mobile devices or participant age. These findings suggest that responses to self-report measures administered via mobile device are equivalent to those obtained via paper and they can be used with experienced as well as naive users of mobile devices. C1 [Price, Matthew] Univ Vermont, Dept Psychol Sci, Burlington, VT 05405 USA. [Kuhn, Eric; Hoffman, Julia E.; Ruzek, Josef] Dept Vet Affairs Palo Alto Hlth Care Syst, Disseminat & Training Div, Natl Ctr PTSD, Palo Alto, CA USA. [Hoffman, Julia E.] Dept Vet Affairs Palo Alto Healthcare Syst, Ctr Healthcare Evaluat, Palo Alto, CA USA. [Acierno, Ron] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Acierno, Ron] Med Univ S Carolina, Charleston, SC 29425 USA. RP Price, M (reprint author), Univ Vermont, Dept Psychol Sci, Burlington, VT 05405 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2015 VL 28 IS 5 BP 480 EP 483 DI 10.1002/jts.22037 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX0KL UT WOS:000365385200015 PM 26375277 ER PT J AU Hu, T Yeh, JE Pinello, L Jacob, J Chakravarthy, S Yuan, GC Chopra, R Frank, DA AF Hu, Tiancen Yeh, Jennifer E. Pinello, Luca Jacob, Jaison Chakravarthy, Srinivas Yuan, Guo-Cheng Chopra, Rajiv Frank, David A. TI Impact of the N-Terminal Domain of STAT3 in STAT3-Dependent Transcriptional Activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE-PHASE RESPONSE; SIGNAL TRANSDUCER; ALPHA-2-MACROGLOBULIN GENE; TYROSINE PHOSPHORYLATION; ACTIVATING STAT3; TARGET GENES; HUMAN TUMORS; BINDING; IDENTIFICATION; CELLS AB The transcription factor STAT3 is constitutively active in many cancers, where it mediates important biological effects, including cell proliferation, differentiation, survival, and angiogenesis. The N-terminal domain (NTD) of STAT3 performs multiple functions, such as cooperative DNA binding, nuclear translocation, and protein-protein interactions. However, it is unclear which subsets of STAT3 target genes depend on the NTD for transcriptional regulation. To identify such genes, we compared gene expression in STAT3-null mouse embryonic fibroblasts (MEFs) stably expressing wild-type STAT3 or STAT3 from which NTD was deleted. NTD deletion reduced the cytokine-induced expression of specific STAT3 target genes by decreasing STAT3 binding to their regulatory regions. To better understand the potential mechanisms of this effect, we determined the crystal structure of the STAT3 NTD and identified a dimer interface responsible for cooperative DNA binding in vitro. We also observed an Ni2+-mediated oligomer with an as yet unknown biological function. Mutations on both dimer and Ni2+-mediated interfaces affected the cytokine induction of STAT3 target genes. These studies shed light on the role of the NTD in transcriptional regulation by STAT3 and provide a structural template with which to design STAT3 NTD inhibitors with potential therapeutic value. C1 [Hu, Tiancen; Jacob, Jaison; Chopra, Rajiv] Novartis Inst BioMed Res, Ctr Prote Chem, Cambridge, MA USA. [Hu, Tiancen] Novartis Inst BioMed Res, Postdoctoral Program, Cambridge, MA USA. [Yeh, Jennifer E.; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yeh, Jennifer E.; Frank, David A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chakravarthy, Srinivas; Frank, David A.] IIT, Biophys Collaborat Access Team, Adv Photon Source, Argonne Natl Lab, Lemont, IL USA. [Pinello, Luca; Yuan, Guo-Cheng; Frank, David A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Pinello, Luca; Yuan, Guo-Cheng; Frank, David A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Frank, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Chopra, R (reprint author), Novartis Inst BioMed Res, Ctr Prote Chem, Cambridge, MA USA. EM rajiv.chopra@novartis.com; david_frank@dfci.harvard.edu RI ID, BioCAT/D-2459-2012 FU National Cancer Institute [R01-CA160979, T32GM007226, F30 CA180340-01]; Brent Leahey Fund; DOE Office of Science [DE-AC02-06CH11357]; National Institute of General Medical Sciences of the National Institutes of Health [P41 GM103622] FX This work was supported by grants from the National Cancer Institute (R01-CA160979, T32GM007226, and F30 CA180340-01) and the Brent Leahey Fund. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. BioCAT is supported by grant P41 GM103622 from the National Institute of General Medical Sciences of the National Institutes of Health. NR 77 TC 3 Z9 3 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2015 VL 35 IS 19 BP 3284 EP 3300 DI 10.1128/MCB.00060-15 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CX0MP UT WOS:000365391300003 PM 26169829 ER PT J AU Martin, NE Gerke, T Sinnott, JA Stack, EC Andren, O Andersson, SO Johansson, JE Fiorentino, M Finn, S Fedele, G Stampfer, M Kantoff, PW Mucci, LA Loda, M AF Martin, Neil E. Gerke, Travis Sinnott, Jennifer A. Stack, Edward C. Andren, Ove Andersson, Swen-Olof Johansson, Jan-Erik Fiorentino, Michelangelo Finn, Stephen Fedele, Giuseppe Stampfer, Meir Kantoff, Philip W. Mucci, Lorelei A. Loda, Massimo TI Measuring PI3K Activation: Clinicopathologic, Immunohistochemical, and RNA Expression Analysis in Prostate Cancer SO MOLECULAR CANCER RESEARCH LA English DT Article ID PTEN TUMOR-SUPPRESSOR; BREAST-CANCER; BIOCHEMICAL RECURRENCE; ANDROGEN RECEPTOR; CELL-PROLIFERATION; UP-REGULATION; PATHWAY; SIGNATURE; GROWTH; RISK AB Assessing the extent of PI3K pathway activity in cancer is vital to predicting sensitivity to PI3K-targeting drugs, but the best biomarker of PI3K pathway activity in archival tumor specimens is unclear. Here, PI3K pathway activation was assessed, in clinical tissue from 1,021 men with prostate cancers, using multiple pathway nodes that include PTEN, phosphorylated AKT (pAKT), phosphorylated ribosomal protein S6 (pS6), and stathmin. Based on these markers, a 9-point score of PI3K activation was created using the combined intensity of the 4-markers and analyzed its association with proliferation (Ki67), apoptosis (TUNEL), and androgen receptor (AR) status, as well as pathologic features and cancer-specific outcomes. In addition, the PI3K activation score was compared with mRNA expression profiling data for a large subset of men. Interestingly, those tumors with higher PI3K activation scores also had higher Gleason grade (P = 0.006), increased AR (r = 0.37; P < 0.001) and Ki67 (r = 0.24; P < 0.001), and decreased TUNEL (r = -0.12; P = 0.003). Although the PI3K activation score was not associated with an increased risk of lethal outcome, a significant interaction between lethal outcome, Gleason and high PI3K score (P = 0.03) was observed. Finally, enrichment of PI3K-specific pathways was found in the mRNA expression patterns differentiating the low and high PI3K activation scores; thus, the 4-marker IHC score of PI3K pathway activity correlates with features of PI3K activation. (C) 2015 AACR. C1 [Martin, Neil E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. [Gerke, Travis; Sinnott, Jennifer A.; Stampfer, Meir; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Sinnott, Jennifer A.; Stampfer, Meir; Mucci, Lorelei A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Div Network Med, Boston, MA 02115 USA. [Stack, Edward C.; Fiorentino, Michelangelo; Finn, Stephen; Fedele, Giuseppe; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Stack, Edward C.; Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Stack, Edward C.; Kantoff, Philip W.; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Andren, Ove; Andersson, Swen-Olof; Johansson, Jan-Erik] Univ Orebro, Sch Med & Hlth Sci, SE-70182 Orebro, Sweden. [Andren, Ove; Andersson, Swen-Olof; Johansson, Jan-Erik] Orebro Univ Hosp, Dept Urol, Orebro, Sweden. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Addarii Inst, Pathol Unit, Bologna, Italy. [Finn, Stephen] Trinity Coll Dublin, Dept Pathol, Dublin, Ireland. [Loda, Massimo] Broad Inst Harvard & MIT, Cambridge, MA USA. [Loda, Massimo] Kings Coll London, Div Canc Studies, London WC2R 2LS, England. RP Martin, NE (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASB-I,L2, Boston, MA 02115 USA. EM nmartin@LROC.harvard.edu OI Finn, Stephen/0000-0002-8628-5814 FU Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Prostate Cancer [P50CA090381-08]; National Cancer Institute of the NIH [UM1CA167552, R01CA141298, R01CA136578, R01CA131945, P01CA89021]; Prostate Cancer Foundation Young Investigator awards FX This study was supported by grants P50CA090381-08 from the Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Prostate Cancer, UM1CA167552, R01CA141298, R01CA136578, R01CA131945, and P01CA89021 from the National Cancer Institute of the NIH, and the Prostate Cancer Foundation Young Investigator awards (to N.E. Martin, S. Finn, and L.A. Mucci). NR 50 TC 2 Z9 2 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2015 VL 13 IS 10 BP 1431 EP 1440 DI 10.1158/1541-7786.MCR-14-0569 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CX3MY UT WOS:000365604300008 PM 26124442 ER PT J AU Miller, MA Zheng, YR Suresh, GW Pfirschke, C Zope, H Engblom, C Kohler, RH Iwamoto, Y Yang, KS Askevold, B Kolishetti, N Pittet, M Lippard, SJ Farokhzad, OC Weissleder, R AF Miller, Miles A. Zheng, Yao-Rong Suresh, Gadde W. Pfirschke, Christina Zope, Harshal Engblom, Camilla Kohler, Rainer H. Iwamoto, Yoshiko Yang, Katherine S. Askevold, Bjorn Kolishetti, Nagesh Pittet, Mikael Lippard, Stephen J. Farokhzad, Omid C. Weissleder, Ralph TI Tumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug SO NATURE COMMUNICATIONS LA English DT Article ID IN-VIVO; CANCER-THERAPY; SINGLE-CELL; LIPOSOMAL DOXORUBICIN; CISPLATIN PRODRUG; TARGETED DELIVERY; OVARIAN-CANCER; BREAST-CANCER; NANOPARTICLES; MODELS AB Therapeutic nanoparticles (TNPs) aim to deliver drugs more safely and effectively to cancers, yet clinical results have been unpredictable owing to limited in vivo understanding. Here we use single-cell imaging of intratumoral TNP pharmacokinetics and pharmacodynamics to better comprehend their heterogeneous behaviour. Model TNPs comprising a fluorescent platinum(IV) pro-drug and a clinically tested polymer platform (PLGA-b-PEG) promote long drug circulation and alter accumulation by directing cellular uptake toward tumourassociated macrophages (TAMs). Simultaneous imaging of TNP vehicle, its drug payload and single-cell DNA damage response reveals that TAMs serve as a local drug depot that accumulates significant vehicle from which DNA-damaging Pt payload gradually releases to neighbouring tumour cells. Correspondingly, TAM depletion reduces intratumoral TNP accumulation and efficacy. Thus, nanotherapeutics co-opt TAMs for drug delivery, which has implications for TNP design and for selecting patients into trials. C1 [Miller, Miles A.; Pfirschke, Christina; Engblom, Camilla; Kohler, Rainer H.; Iwamoto, Yoshiko; Yang, Katherine S.; Askevold, Bjorn; Pittet, Mikael; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Zheng, Yao-Rong; Lippard, Stephen J.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Suresh, Gadde W.; Zope, Harshal; Kolishetti, Nagesh; Farokhzad, Omid C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Nanomed & Biomat,Dept Anesthesiol, Boston, MA 02115 USA. [Farokhzad, Omid C.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu RI Kolishetti, Nagesh/K-2810-2012; Gadde, Suresh/B-9483-2012 OI Kolishetti, Nagesh/0000-0001-5574-673X; Gadde, Suresh/0000-0001-9102-3029 FU US National Institutes of Health (NIH) [RO1-CA164448, P50-CA086355, PO1-CA139980, U54-CA151884]; National Cancer Institute [RO1-CA034992]; David Koch-PCF Program in Nanotherapeutics; Deutsche Forschungsgemeinschaft (DFG) [PF809/1-1] FX This work was supported in part by the US National Institutes of Health (NIH) grants RO1-CA164448, P50-CA086355, PO1-CA139980, U54-CA151884 (to R.W.) and RO1-CA034992 from the National Cancer Institute (to SJL), along with the David Koch-PCF Program in Nanotherapeutics (to O.C.F.). C.P. is supported by the Deutsche Forschungsgemeinschaft (DFG) PF809/1-1. We thank Dr Kevin King, Dr Julia Kalow, Dr Basit Yameen, Alex Zaltsman, Matthew Sebas, Greg Wojtkiewicz, David Pirovich and Olivier Kister for technical assistance, and Dr Melissa Sprachman for helpful discussions. NR 70 TC 27 Z9 27 U1 29 U2 82 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2015 VL 6 AR 8692 DI 10.1038/ncomms9692 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW4CA UT WOS:000364937600006 PM 26503691 ER PT J AU Nielson, JL Paquette, J Liu, AW Guandique, CF Tovar, CA Inoue, T Irvine, KA Gensel, JC Kloke, J Petrossian, TC Lum, PY Carlsson, GE Manley, GT Young, W Beattie, MS Bresnahan, JC Ferguson, AR AF Nielson, Jessica L. Paquette, Jesse Liu, Aiwen W. Guandique, Cristian F. Tovar, C. Amy Inoue, Tomoo Irvine, Karen-Amanda Gensel, John C. Kloke, Jennifer Petrossian, Tanya C. Lum, Pek Y. Carlsson, Gunnar E. Manley, Geoffrey T. Young, Wise Beattie, Michael S. Bresnahan, Jacqueline C. Ferguson, Adam R. TI Topological data analysis for discovery in preclinical spinal cord injury and traumatic brain injury SO NATURE COMMUNICATIONS LA English DT Article ID KNOWLEDGE-BASED APPROACH; CELL-DEATH; BIG DATA; RATING-SCALE; RATS; MECHANISMS; CONSEQUENCES; DEGENERATION; NEUROSCIENCE; TRANSLATION AB Data-driven discovery in complex neurological disorders has potential to extract meaningful syndromic knowledge from large, heterogeneous data sets to enhance potential for precision medicine. Here we describe the application of topological data analysis (TDA) for data-driven discovery in preclinical traumatic brain injury (TBI) and spinal cord injury (SCI) data sets mined from the Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI) repository. Through direct visualization of inter-related histopathological, functional and health outcomes, TDA detected novel patterns across the syndromic network, uncovering interactions between SCI and co-occurring TBI, as well as detrimental drug effects in unpublished multicentre preclinical drug trial data in SCI. TDA also revealed that perioperative hypertension predicted long-term recovery better than any tested drug after thoracic SCI in rats. TDA-based data-driven discovery has great potential application for decision-support for basic research and clinical problems such as outcome assessment, neurocritical care, treatment planning and rapid, precision-diagnosis. C1 [Nielson, Jessica L.; Liu, Aiwen W.; Guandique, Cristian F.; Manley, Geoffrey T.; Beattie, Michael S.; Bresnahan, Jacqueline C.; Ferguson, Adam R.] Univ Calif San Francisco, Brain & Spinal Injury Ctr, Dept Neurosurg, San Francisco, CA 94143 USA. [Paquette, Jesse] Tagb Io, San Francisco, CA 94131 USA. [Tovar, C. Amy] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA. [Inoue, Tomoo] Tohoku Univ, Grad Sch Med, Dept Neurosurg, Sendai, Miyagi 9800856, Japan. [Irvine, Karen-Amanda] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Neurol, San Francisco, CA 94110 USA. [Gensel, John C.] Univ Kentucky, Chandler Med Ctr, Spinal Cord & Brain Injury Res Ctr, Dept Physiol, Lexington, KY 40536 USA. [Kloke, Jennifer; Carlsson, Gunnar E.] Ayasdi Inc, Menlo Pk, CA 94025 USA. [Petrossian, Tanya C.] GenePeeks Inc, New York, NY 10001 USA. [Lum, Pek Y.] Capella Biosci, Palo Alto, CA 94301 USA. [Carlsson, Gunnar E.] Stanford Univ, Dept Math, Stanford, CA 94305 USA. [Young, Wise] Rutgers State Univ, Dept Cell Biol & Neurosci, WM Keck Ctr Collaborat Neurosci, Piscataway, NJ 08854 USA. [Ferguson, Adam R.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Neurosurg, San Francisco, CA 94110 USA. RP Ferguson, AR (reprint author), Univ Calif San Francisco, Brain & Spinal Injury Ctr, Dept Neurosurg, 1001 Potrero Ave,Bldg 1,Room 101, San Francisco, CA 94143 USA. EM adam.ferguson@ucsf.edu OI Nielson, Jessica/0000-0002-3677-3959 FU Craig H. Neilsen Foundation [224308]; National Institutes of Health (NIH) [NS067092, NS069537, NS038079, NS031193, AG032518, NS079030, NS032000]; NYSCoRE [CO19772]; Department of Defense (DoD) [W81XWH-10-1-0910, W81XWH-13-1-0297]; Wings for Life Foundation [WFLUS008/12, WFLUS006/14] FX This work was funded by the Craig H. Neilsen Foundation Grant 224308, the National Institutes of Health (NIH) NS067092 (A.R.F.), NS069537 (A.R.F), NS038079 (J.C.B. and M.S.B.), NS031193 and AG032518 (M.S.B. and J.C.B.), NS079030 (J.L.N.), NS032000 (W.Y.; M.S.B. site PI, multicentre study); NYSCoRE CO19772 (M.S.B. and J.C.B.), the Department of Defense (DoD) grants W81XWH-10-1-0910 (M.S.B.) and W81XWH-13-1-0297 (M.S.B.), and Wings for Life Foundation grants WFLUS008/12 and WFLUS006/14 (A.R.F.). We thank J.R. Huie and J. Haefeli for useful comments, and A. Lin and S. Visuthikraisee for technical support. NR 55 TC 8 Z9 8 U1 5 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2015 VL 6 AR 8581 DI 10.1038/ncomms9581 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW4AD UT WOS:000364932600028 PM 26466022 ER PT J AU Reddy, L Poncet, M Self, MW Peters, JC Douw, L van Dellen, E Claus, S Reijneveld, JC Baayen, JC Roelfsema, PR AF Reddy, Leila Poncet, Marlene Self, Matthew W. Peters, Judith C. Douw, Linda van Dellen, Edwin Claus, Steven Reijneveld, Jaap C. Baayen, Johannes C. Roelfsema, Pieter R. TI Learning of anticipatory responses in single neurons of the human medial temporal lobe SO NATURE COMMUNICATIONS LA English DT Article ID MONKEY INFEROTEMPORAL CORTEX; LONG-TERM-MEMORY; HUMAN HIPPOCAMPUS; HUMAN BRAIN; OBJECT REPRESENTATIONS; INDIVIDUAL NEURONS; CONCEPT CELLS; ASSOCIATIONS; REGULARITIES; RECOGNITION AB Neuronal processes underlying the formation of new associations in the human brain are not yet well understood. Here human participants, implanted with depth electrodes in the brain, learned arbitrary associations between images presented in an ordered, predictable sequence. During learning we recorded from medial temporal lobe (MTL) neurons that responded to at least one of the pictures in the sequence (the preferred stimulus). We report that as a result of learning, single MTL neurons show asymmetric shifts in activity and start firing earlier in the sequence in anticipation of their preferred stimulus. These effects appear relatively early in learning, after only 11 exposures to the stimulus sequence. The anticipatory neuronal responses emerge while the subjects became faster in reporting the next item in the sequence. These results demonstrate flexible representations that could support learning of new associations between stimuli in a sequence, in single neurons in the human MTL. C1 [Reddy, Leila; Poncet, Marlene] Univ Toulouse 3, Ctr Rech Cerveau & Cognit, Univ Toulouse, F-31052 Toulouse, France. [Reddy, Leila; Poncet, Marlene] CNRS, UMR 5549, Fac Med Purpan, F-31052 Toulouse, France. [Self, Matthew W.; Roelfsema, Pieter R.] Netherlands Inst Neurosci KNAW, Dept Vis & Cognit, NL-1105 BA Amsterdam, Netherlands. [Peters, Judith C.] Royal Netherlands Acad Arts & Sci KNAW, Neuroimaging & Neuromodeling Grp, Inst Neurosci, NL-1105 BA Amsterdam, Netherlands. [Peters, Judith C.] Maastricht Univ, Fac Psychol & Neurosci, Dept Cognit Neurosci, NL-6200 MD Maastricht, Netherlands. [Douw, Linda] Vrije Univ Amsterdam, Med Ctr, Dept Anat & Neurosci, NL-1081 BT Amsterdam, Netherlands. [Douw, Linda] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [van Dellen, Edwin] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3508 GA Utrecht, Netherlands. [van Dellen, Edwin] Vrije Univ Amsterdam, Med Ctr, Dept Neurophysiol, NL-1007 MB Amsterdam, Netherlands. [Claus, Steven] Stichting Epilepsie Instellingen Nederland, NL-2103 SW Heemstede, Netherlands. [Claus, Steven; Reijneveld, Jaap C.] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands. [Baayen, Johannes C.] Vrije Univ Amsterdam, Med Ctr, Dept Neurosur, NL-1007 MB Amsterdam, Netherlands. [Roelfsema, Pieter R.] Vrije Univ, Ctr Neurogenom & Cognit Res, Dept Integrat Neurophysiol, NL-1081 HV Amsterdam, Netherlands. [Roelfsema, Pieter R.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. RP Reddy, L (reprint author), Univ Toulouse 3, Ctr Rech Cerveau & Cognit, Univ Toulouse, F-31052 Toulouse, France. EM leila.reddy@cerco.ups-tlse.fr OI Self, Matthew/0000-0001-5731-579X; Roelfsema, Pieter/0000-0002-1625-0034 FU Fyssen foundation; Universite' Paul Sabatier, Toulouse, France (BQR); Universite' Paul Sabatier, Toulouse, France (Appel a' Projets de Recherche Labellise's); French Agence Nationale de la Recherche (ANR-JCJC); European Research Council (ERC) [339490]; Neuroscience Campus Amsterdam proof of concept funding; Dutch Epilepsy Foundation [08-08, 09-09] FX We are grateful to Benedikt Zoefel for his help in obtaining some of the data reported here, and to the entire staff of the EMU of the VUmc for their help during these recordings. In particular we would like to thank Peterjan Ris and Hanneke Ronner for their technical assistance, and Demetrios Velis for invaluable help with planning the patient workup and implantation design. We are also grateful to Ruud Joosten for his help in setting up the recordings and C.J. Stam for his help with obtaining ethics approval. We thank K. Diba, M. Mehta, B. Poucet, C.J. Stam and R. VanRullen for helpful comments on the manuscript. This work was supported by grants from the Fyssen foundation, the Universite' Paul Sabatier, Toulouse, France (BQR, 2009 and Appel a' Projets de Recherche Labellise's, 2013) and the French Agence Nationale de la Recherche (ANR-JCJC) to L.R., and the European Research Council (ERC Grant Agreement no. 339490) and Neuroscience Campus Amsterdam proof of concept funding to P.R.E.v.D, L.D and J.C.R were funded by the Dutch Epilepsy Foundation (grant 08-08 to L.D. and J.C.R., and grant 09-09 to E.v.D and J.C.R). NR 46 TC 3 Z9 3 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2015 VL 6 AR 8556 DI 10.1038/ncomms9556 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW4AD UT WOS:000364932600003 PM 26449885 ER PT J AU Prabhakar, S Zhang, X Goto, J Han, S Lai, C Bronson, R Sena-Esteves, M Ramesh, V Stemmer-Rachamimov, A Kwiatkowski, DJ Breakefield, XO AF Prabhakar, Shilpa Zhang, Xuan Goto, June Han, Sangyeul Lai, Charles Bronson, Roderick Sena-Esteves, Miguel Ramesh, Vijaya Stemmer-Rachamimov, Anat Kwiatkowski, David J. Breakefield, Xandra O. TI Survival benefit and phenotypic improvement by hamartin gene therapy in a tuberous sclerosis mouse brain model SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Tuberous sclerosis complex; TSC; TSC1; TSC2; Gene therapy; AAV; Neuron ID GIANT-CELL ASTROCYTOMAS; CENTRAL-NERVOUS-SYSTEM; NONHUMAN-PRIMATES; MAMMALIAN TARGET; COMPLEX; RAPAMYCIN; TSC1; MICE; LYMPHANGIOLEIOMYOMATOSIS; VECTORS AB We examined the potential benefit of gene therapy in a mouse model of tuberous sclerosis complex (TSC) in which there is embryonic loss of Tsc1 (hamartin) in brain neurons. An adeno-associated virus (AAV) vector (serotype rh8) expressing a tagged form of hamartin was injected into the cerebral ventricles of newborn pups with the genotype Tsc1(cc) (homozygous for a conditional foxed Tsc1 allele) SynI-cre(+), in which Tsc1 is lost selectively in neurons starting at embryonic day 12. Vector-treated Tscl(cc)SynIcre(+) mice showed a marked improvement in survival from a mean of 22 days in non-injected mice to 52 days in AAV hamartin vector-injected mice, with improved weight gain and motor behavior in the latter. Pathologic studies showed normalization of neuron size and a decrease in markers of mTOR activation in treated as compared to untreated mutant littermates. Hence, we show that gene replacement in the brain is an effective therapeutic approach in this mouse model of TSC1. Our strategy for gene therapy has the advantages that therapy can be achieved from a single application, as compared to repeated treatment with drugs, and that AAV vectors have been found to have minimal to no toxicity in clinical trials for other neurologic conditions. Although there are many additional issues to be addressed, our studies support gene therapy as a useful approach in TSC patients. (C) 2015 Elsevier Inc. All rights reserved. C1 [Prabhakar, Shilpa; Zhang, Xuan; Lai, Charles; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Prabhakar, Shilpa; Zhang, Xuan; Lai, Charles; Breakefield, Xandra O.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02114 USA. [Prabhakar, Shilpa; Zhang, Xuan; Lai, Charles; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Goto, June; Kwiatkowski, David J.] Harvard Univ, Sch Med, Dept Med, Translat Med Div,Brigham & Womens Hosp, Boston, MA USA. [Han, Sangyeul; Ramesh, Vijaya] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Bronson, Roderick] Harvard Univ, Sch Med, Rodent Histopathol Core Facil, Boston, MA USA. [Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Dept Neurol, Gene Therapy Ctr, Worcester, MA USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kwiatkowski, DJ (reprint author), Brigham & Womens Hosp, Div Pulm Med, 1 Blackfan Circle,Room 6-213, Boston, MA 02115 USA. EM dk@rics.bwh.harvard.edu; breakefleld@hms.harvard.edu RI Lai, Charles/D-5442-2017 FU NIH/NINDS [NS024279]; DOD Army Grant [W81XWH-13-1-0076]; NIH [NINDSP30 NSO45776]; European Commission [602391-2] FX We thank Ms. Suzanne McDavitt for her skilled editorial assistance; Michelle Forrestall Lee, Medical Photographer in Pathology Media Lab, MGH for the imaging training; Tao Qin, Laboratory Researcher in Department of Neurology, MGH for the Image J training; Mei Huan Lin for genotyping of the mice by MLPA analysis, DNA Core facility, Brigham and Women's Hospital, Boston, MA; Dr. Daniel Joyner, Department of Neurology, Alzheimer's Disease Research Unit, MGH, Charlestown, MA, for mouse neuronal cultures; Dr. Davide Gianni and MS-E, Vector Core, Gene Therapy Center, UMASS Medical School, Worcester, MA for AAV-hamartin vector packaging; and Ms. Danielle Morse and Dr. Bakhos Tannous, Vector Core, MGH, Charlestown, MA for AAV-GFP vector packaging. This work was supported by NIH/NINDS NS024279 (XOB, SP, AS-R, DJK); DOD Army Grant W81XWH-13-1-0076 (XOB and SP); NIH NINDSP30 NSO45776 (XOB and SP); and the European Commission (602391-2) (DJK). NR 52 TC 2 Z9 2 U1 3 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2015 VL 82 BP 22 EP 31 DI 10.1016/j.nbd.2015.04.018 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CW4RO UT WOS:000364980000003 PM 26019056 ER PT J AU Teng, E Taylor, K Bilousova, T Weiland, D Pham, T Zuo, XH Yang, FS Chen, PP Glabe, CG Takacs, A Hoffman, DR Frautschy, SA Cole, GM AF Teng, Edmond Taylor, Karen Bilousova, Tina Weiland, David Thaidan Pham Zuo, Xiaohong Yang, Fusheng Chen, Ping-Ping Glabe, Charles G. Takacs, Alison Hoffman, Dennis R. Frautschy, Sally A. Cole, Gregory M. TI Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and A beta pathology and modulates A beta oligomerization SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Docosahexaenoic acid; beta-amyloid; Aggregation; Oligomers; Fibrillar; Prefibrillar; Hippocampus; Transgenic; Alzheimer's disease ID MILD COGNITIVE IMPAIRMENT; POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; ALZHEIMERS-DISEASE; AMYLOID-BETA; DOCOSAHEXAENOIC ACID; MOUSE MODEL; DOUBLE-BLIND; IN-VITRO; SYNAPTIC PLASTICITY AB Increased dietary consumption of docosahexaenoic acid (DHA) is associated with decreased risk for Alzheimer's disease (AD). These effects have been postulated to arise from DHA's pleiotropic effects on AD pathophysiology, including its effects on beta-amyloid (A beta) production, aggregation, and toxicity. While in vitro studies suggest that DHA may inhibit and reverse the formation of toxic A beta oligomers, it remains uncertain whether these mechanisms operate in vivo at the physiological concentrations of DHA attainable through dietary supplementation. We sought to clarify the effects of dietary DHA supplementation on A beta indices in a transgenic APP/PS1 rat model of AD. Animals maintained on a DHA-supplemented diet exhibited reductions in hippocampal A beta plaque density and modest improvements on behavioral testing relative to those maintained on a DHA-depleted diet. However, DHA supplementation also increased overall soluble A beta oligomer levels in the hippocampus. Further quantification of specific conformational populations of A beta oligomers indicated that DHA supplementation increased fibrillar (i.e. putatively less toxic) A beta oligomers and decreased prefibrillar (i.e. putatively more toxic) A beta oligomers. These results provide in vivo evidence suggesting that DHA can modulate A beta aggregation by stabilizing soluble fibrillar A beta oligomers and thus reduce the formation of both A beta plaques and prefibrillar AS oligomers. However, since fibrillar A beta oligomers still retain inherent neurotoxicity, DHA may need to be combined with other interventions that can additionally reduce fibrillar A beta oligomer levels for more effective prevention of AD in clinical settings. Published by Elsevier Inc. C1 [Teng, Edmond; Taylor, Karen; Bilousova, Tina; Weiland, David; Thaidan Pham; Zuo, Xiaohong; Yang, Fusheng; Chen, Ping-Ping; Frautschy, Sally A.; Cole, Gregory M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. [Teng, Edmond; Weiland, David; Zuo, Xiaohong; Yang, Fusheng; Chen, Ping-Ping; Frautschy, Sally A.; Cole, Gregory M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Zuo, Xiaohong] Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Dept Neurobiol & Neurol, Beijing, Peoples R China. [Glabe, Charles G.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. [Glabe, Charles G.] King Abdulaziz Univ, King Fahd Med Res Ctr, Dept Biochem, Jeddah 21413, Saudi Arabia. [Glabe, Charles G.] King Abdulaziz Univ, King Fahd Med Res Ctr, Expt Biochem Unit, Jeddah 21413, Saudi Arabia. [Takacs, Alison; Hoffman, Dennis R.] Retina Fdn Southwest, Dallas, TX USA. [Hoffman, Dennis R.] UT Southwestern Med Ctr, Dept Ophthalmol, Dallas, TX USA. RP Teng, E (reprint author), West Los Angeles VA Healthcare Ctr, Neurobehav Serv 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu RI Zuo, Xiaohong/H-6254-2016 FU National Institute on Aging [K08 AG34628, RC1 AG035878]; NIA; AFAR; John A. Hartford Foundation; Atlantic Philanthropies; Starr Foundation FX This work was supported by the National Institute on Aging (K08 AG34628 [to ET; jointly sponsored by NIA, AFAR, the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation and an anonymous donor] and RC1 AG035878 [to GMC]). We would like to thank Eric Y. Haden for cross-linked A beta oligomers, Christopher C. Giza for behavioral testing space, and Ta-Lee Teng for technical assistance. NR 70 TC 3 Z9 3 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2015 VL 82 BP 552 EP 560 DI 10.1016/j.nbd.2015.09.002 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CW4RO UT WOS:000364980000052 PM 26369878 ER PT J AU Bakshi, R Zhang, H Logan, R Joshi, I Xu, YH Chen, XQ Schwarzschild, MA AF Bakshi, Rachit Zhang, Hong Logan, Robert Joshi, Ila Xu, Yuehang Chen, Xiqun Schwarzschild, Michael A. TI Neuroprotective effects of urate are mediated by augmenting astrocytic glutathione synthesis and release SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Astrocytes; Glutathione; Neurons; Nrf2; Urate ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; URIC-ACID PROTECTS; OXIDATIVE STRESS; PARKINSONS-DISEASE; GENE-EXPRESSION; PC12 CELLS; NEURONS; BRAIN; METABOLISM; PATHWAY AB Urate has emerged as a promising target for neuroprotection based on epidemiological observations, preclinical models, and early clinical trial results in multiple neurologic diseases, including Parkinson's disease (PD). This study investigates the astrocytic mechanism of urate's neuroprotective effect. Targeted biochemical screens of conditioned medium from urate- versus vehicle-treated astrocytes identified markedly elevated glutathione (GSH) concentrations as a candidate mediator of urate's astrocyte-dependent neuroprotective effects. Urate treatment also induced the nuclear translocation of the nuclear factor (eiythroid-derived 2)-like 2 (Nr12) protein and transcriptional activation of its key target genes in primary astrocytic cultures. Urate's neuroprotective effect was attenuated when GSH was depleted in the conditioned media either by targeting its synthesis or release by astrocytes. Overall, these results implicate GSH as the extracellular astrocytic factor mediating the protective effect of urate in a cellular model of PD. These results also show that urate can employ a novel indirect neuroprotective mechanism via induction of the Nr12 signaling pathway, a master regulator of the response to oxidative stress, in astrocytes. (C) 2015 Elsevier Inc. All rights reserved. C1 [Bakshi, Rachit; Zhang, Hong; Logan, Robert; Xu, Yuehang; Chen, Xiqun; Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. [Zhang, Hong] Capital Med Univ, Dept Neurobiol, Key Lab Neurodegenerat Dis, Minist Educ, Beijing 100069, Peoples R China. [Joshi, Ila] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02129 USA. RP Bakshi, R (reprint author), Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Mol Neurobiol Lab, 114 16th St, Boston, MA 02129 USA. EM rbakshi1@mgh.harvard.edu FU Department of Defense/NETPR program [W81XWH-11-1-0150]; NIH [K24NS060991, R21 NS084710]; Granite State Development; National Natural Science Foundation of China [81372587, 81171886] FX This study was funded by the Department of Defense/NETPR program W81XWH-11-1-0150, NIH K24NS060991, R21 NS084710 and Granite State Development. A visiting fellowship supporting Hong Zhang was funded by the National Natural Science Foundation of China (No: 81372587, 81171886). We thank Michael Maguire for mouse husbandry and cell line maintenance. NR 45 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2015 VL 82 BP 574 EP 579 DI 10.1016/j.nbd.2015.08.022 PG 6 WC Neurosciences SC Neurosciences & Neurology GA CW4RO UT WOS:000364980000054 PM 26341543 ER PT J AU Zoppoli, G Gundem, G Pruneri, G Larsimon, D Fornili, M Fumagalli, D Brown, D Salgado, R Van Brussel, T Lambrechts, D Bose, R Metzger, O Galant, C Bertucci, F Piccart, M Biganzoli, E Viale, G Campbell, PJ Sotiriou, C Desmedt, C AF Zoppoli, G. Gundem, G. Pruneri, G. Larsimon, D. Fornili, M. Fumagalli, D. Brown, D. Salgado, R. Van Brussel, T. Lambrechts, D. Bose, R. Metzger, O. Galant, C. Bertucci, F. Piccart, M. Biganzoli, E. Viale, G. Campbell, P. J. Sotiriou, C. Desmedt, C. TI Genomic hallmarks of invasive lobular breast carcinoma and their clinical relevance SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 17th National Congress of Medical Oncology CY OCT 23-25, 2015 CL Rome, ITALY C1 [Zoppoli, G.] Univ Genoa, Genoa, Italy. [Zoppoli, G.] AOU IRCCS San Martino IST, Genoa, Italy. [Gundem, G.; Campbell, P. J.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, Cambs, England. [Pruneri, G.; Viale, G.] European Inst Oncol, Div Pathol, Milan, Italy. [Larsimon, D.] Inst Jules Bordet, Dept Pathol, B-1000 Brussels, Belgium. [Fornili, M.; Biganzoli, E.] Unit Med Stat Biometry & Bioinformat, Milan, Italy. [Fumagalli, D.; Brown, D.; Salgado, R.; Sotiriou, C.; Desmedt, C.] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab, Brussels, Belgium. [Fumagalli, D.; Salgado, R.] Breast Int Grp, Brussels, Belgium. [Van Brussel, T.; Lambrechts, D.] Katholieke Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium. [Van Brussel, T.; Lambrechts, D.] VIB, Vesalius Res Ctr, Leuven, Belgium. [Bose, R.] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. [Bose, R.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [Metzger, O.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Galant, C.] Clin Univ St Luc, Dept Pathol, B-1200 Brussels, Belgium. [Bertucci, F.] Inst J Paoli I Calmettes, Dept Mol Oncol, F-13009 Marseille, France. [Piccart, M.] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2015 VL 26 SU 6 MA A01 BP 3 EP 3 PG 1 WC Oncology SC Oncology GA CW7EA UT WOS:000365159600006 ER PT J AU Wolchok, JD Chiarion-Sileni, V Gonzalez, R Rutkowski, P Grob, J Cowey, CL Lao, CD Schadendorf, D Ferrucci, PF Smylie, M Dummer, R Hill, A Haanen, J Maio, M McArthur, G Yang, A Rollin, L Horak, C Larkin, J Hodi, FS AF Wolchok, J. D. Chiarion-Sileni, V. Gonzalez, R. Rutkowski, P. Grob, J. Cowey, C. L. Lao, C. D. Schadendorf, D. Ferrucci, P. F. Smylie, M. Dummer, R. Hill, A. Haanen, J. Maio, M. McArthur, G. Yang, A. Rollin, L. Horak, C. Larkin, J. Hodi, F. S. TI CheckMate 067: a phase III randomized double-blind study of nivolumab (NIVO) monotherapy or NIVO combined with ipilimumab (IPI) versus IPI monotherapy in previously untreated patients (pts) with advanced melanoma (MEL) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 17th National Congress of Medical Oncology CY OCT 23-25, 2015 CL Rome, ITALY C1 [Wolchok, J. D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wolchok, J. D.] Weill Cornell Med Coll, New York, NY USA. [Chiarion-Sileni, V.] IRCCS, Oncol Inst Veneto, Padua, Italy. [Gonzalez, R.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Rutkowski, P.] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Rutkowski, P.] Inst Oncol, Warsaw, Poland. [Grob, J.] Hosp Timone, Marseille, France. [Cowey, C. L.] Texas Oncol Baylor Charles Sammons Canc Ctr, Dallas, TX USA. [Lao, C. D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Schadendorf, D.] Univ Essen Gesamthsch, Dept Dermatol, Essen, Germany. [Ferrucci, P. F.] European Inst Oncol, Milan, Italy. [Smylie, M.] Cross Canc Inst, Edmonton, AB, Canada. [Dummer, R.] Univ Spital Zurich, Zurich, Switzerland. [Hill, A.] Tasman Oncol Res, Gold Coast, Qld, Australia. [Haanen, J.] Netherlands Canc Inst, Amsterdam, Netherlands. [Maio, M.] Univ Hosp Siena, Siena, Italy. [McArthur, G.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Yang, A.; Horak, C.] Bristol Myers Squibb Co, Princeton, NJ USA. [Rollin, L.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Larkin, J.] Royal Marsden Hosp, London SW3 6JJ, England. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2015 VL 26 SU 6 MA B08 BP 28 EP 28 PG 1 WC Oncology SC Oncology GA CW7EA UT WOS:000365159600089 ER PT J AU Casali, PG Reichardt, P Kang, Y Blay, J Joensuu, H Maki, RG Rutkowski, P Hohenberger, P Gelderblom, H Leahy, MG von Mehren, M Schoffski, P Blackstein, ME Le Cesne, A Badalamenti, G Xu, J Nishida, T Laurent, D Kuss, I Demetri, GD AF Casali, P. G. Reichardt, P. Kang, Y. Blay, J. Joensuu, H. Maki, R. G. Rutkowski, P. Hohenberger, P. Gelderblom, H. Leahy, M. G. von Mehren, M. Schoffski, P. Blackstein, M. E. Le Cesne, A. Badalamenti, G. Xu, J. Nishida, T. Laurent, D. Kuss, I. Demetri, G. D. TI Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 17th National Congress of Medical Oncology CY OCT 23-25, 2015 CL Rome, ITALY C1 [Casali, P. G.] Fdn IRCCS, Ist Nazl Tumori, Milan, Italy. [Reichardt, P.] HELIOS Klinikum Berlin Buch, Berlin, Germany. [Kang, Y.] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. [Blay, J.] Ctr Leon Berard, F-69373 Lyon, France. [Joensuu, H.] Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Helsinki, Finland. [Maki, R. G.] Mt Sinai Sch Med, New York, NY USA. [Rutkowski, P.] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Rutkowski, P.] Inst Oncol, Warsaw, Poland. [Hohenberger, P.] Univ Mannheim, Med Ctr, Dept Surg, D-68131 Mannheim, Germany. [Gelderblom, H.] Leiden Univ Med Ctr, Dept Clin Oncol, Leiden, Netherlands. [Leahy, M. G.] Christie NHS Fdn Trust, Manchester, Lancs, England. [von Mehren, M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Schoffski, P.] Univ Ziekenhuis Gasthuisberg, Leuven, Belgium. [Blackstein, M. E.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Le Cesne, A.] Inst Gustave Roussy, Villejuif, France. [Badalamenti, G.] Univ Palermo, Div Med Oncol, Dept Oncol, Palermo, Italy. [Xu, J.] Acad Mil Med Sci, Affiliated Hosp, Beijing, Peoples R China. [Nishida, T.] Osaka Police Hosp, Dept Surg, Osaka, Japan. [Laurent, D.; Kuss, I.] Bayer HealthCare Pharmaceut, Berlin, Germany. [Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2015 VL 26 SU 6 MA C01 BP 29 EP 29 PG 1 WC Oncology SC Oncology GA CW7EA UT WOS:000365159600091 ER PT J AU Bracarda, S Procopio, G Parker, C Tombal, B Miller, K Saad, F Fang, F Zhang, A Kornacker, M Higano, C Smith, MR AF Bracarda, S. Procopio, G. Parker, C. Tombal, B. Miller, K. Saad, F. Fang, F. Zhang, A. Kornacker, M. Higano, C. Smith, M. R. TI Era 223-A Phase 3 Trial of Radium-223 Dichloride (Ra-223) in Combination with Abiraterone Acetate (Aa) and prednisone in the treatment of asymptomatic or mildly symptomatic chemotherapynaive patients with bone-predominant metastatic Castration Resistant Prostate Cancer (Crpc) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 17th National Congress of Medical Oncology CY OCT 23-25, 2015 CL Rome, ITALY C1 [Bracarda, S.] S Donato Hosp, ITT, Dept Oncol, Arezzo, Italy. [Procopio, G.] Fdn IRCCS Ist Nazl Tumori, Dept Oncol, Milan, Italy. [Parker, C.] Royal Marsden NHS Fdn Trust, Acad Urol, Sutton, Surrey, England. [Parker, C.] Inst Canc Res, Sutton, Surrey, England. [Tombal, B.] Clin Univ St Luc, Div Urol, B-1200 Brussels, Belgium. [Miller, K.] Charite, Dept Urol, Berlin, Germany. [Saad, F.] Univ Montreal, Ctr Hosp, Surg Urol, Montreal, PQ, Canada. [Fang, F.] Bayer HealthCare, Global Clin Stat, Whippany, NJ USA. [Zhang, A.] Bayer HealthCare, Oncol, Whippany, NJ USA. [Kornacker, M.] Bayer Pharma AG, Clin Dev Oncol 2, Berlin, Germany. [Higano, C.] Univ Washington, Med Oncol, Seattle, WA 98195 USA. [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Hematol Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2015 VL 26 SU 6 MA F13 BP 57 EP 57 PG 1 WC Oncology SC Oncology GA CW7EA UT WOS:000365159600174 ER PT J AU Antonia, SJ Bendell, J Taylor, M Calvo, E Jager, D de Braud, F Ott, PA Pietanza, MC Horn, L Le, DT Morse, MA Lopez-Martin, JA Ascierto, PA Christensen, O Grosso, JF Simon, J Lin, C Eder, JP AF Antonia, S. J. Bendell, J. Taylor, M. Calvo, E. Jaeger, D. de Braud, F. Ott, P. A. Pietanza, M. C. Horn, L. Le, D. T. Morse, M. A. Lopez-Martin, J. A. Ascierto, P. A. Christensen, O. Grosso, J. F. Simon, J. Lin, C. Eder, J. P. TI Phase 1/2 study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 17th National Congress of Medical Oncology CY OCT 23-25, 2015 CL Rome, ITALY C1 [Antonia, S. J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Bendell, J.] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. [Taylor, M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Calvo, E.] START Madrid, Madrid, Spain. [Jaeger, D.] Univ Heidelberg Hosp, Heidelberg, Germany. [de Braud, F.] Ist Nazl Tumori, I-20133 Milan, Italy. [Ott, P. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pietanza, M. C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Horn, L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Le, D. T.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Morse, M. A.] Duke Univ, Med Ctr, Durham, NC USA. [Lopez-Martin, J. A.] Hosp Univ 12 Octubre, Madrid, Spain. [Ascierto, P. A.] Fdn Pascale, Ist Nazl Tumori, Naples, Italy. [Christensen, O.; Grosso, J. F.; Simon, J.; Lin, C.] Bristol Myers Squibb Co, Princeton, NJ USA. [Eder, J. P.] Yale Comprehens Canc Ctr, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2015 VL 26 SU 6 MA H05 BP 74 EP 75 PG 2 WC Oncology SC Oncology GA CW7EA UT WOS:000365159600231 ER PT J AU Cascinu, S Aprile, G Pastorelli, D Pinto, C Bordonaro, R Farina, G Amoroso, D Bilancia, D Ciuffreda, L Sartori, D Falcone, A Silvestris, N Beretta, GD Buonadonna, A Sobrero, A Tamburini, E Amoroso, V Hsu, Y Chandrawansa, K Wilke, H Fuchs, C Passalacqua, R AF Cascinu, S. Aprile, G. Pastorelli, D. Pinto, C. Bordonaro, R. Farina, G. Amoroso, D. Bilancia, D. Ciuffreda, L. Sartori, D. Falcone, A. Silvestris, N. Beretta, G. D. Buonadonna, A. Sobrero, A. Tamburini, E. Amoroso, V. Hsu, Y. Chandrawansa, K. Wilke, H. Fuchs, C. Passalacqua, R. TI Age subgroup analysis of efficacy and safety data from two phase 3 studies of second-line ramucirumab (RAM) versus placebo (PL) in patients (pts) with previously treated gastric or gastroesophageal junction (GEJ) adenocarcinoma (RAINBOW and REGARD) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 17th National Congress of Medical Oncology CY OCT 23-25, 2015 CL Rome, ITALY C1 [Cascinu, S.] AOU Umberto I Lancisi Salesi, Ancona, Italy. [Aprile, G.] Azienda Osped Univ, Dipartimento Oncol, Udine, Italy. [Pastorelli, D.] Ist Oncol Veneto IRCCS, SSD Oncol Tumori Rari & Miscellanea, Padua, Italy. [Pinto, C.] Azienda Osped Univ, Dipartimento Oncol, Parma, Italy. [Bordonaro, R.] Garibaldi Hosp, UOC Oncol Med, Catania, Italy. [Farina, G.] Azienda Osped Fatebenefratelli & Oftalm, Milan, Italy. [Amoroso, D.] Osped Versilia, UOC Oncol Med, Lido Di Camaiore, LU, Italy. [Amoroso, D.] Osped Versilia, Dip Oncol, Lido Di Camaiore, LU, Italy. [Bilancia, D.] Azienda Osped S Carlo, Unita Operat, UOC Oncol Med, Potenza, Italy. [Ciuffreda, L.] AOU San Giovanni Battista Molinette, SC Oncol Med 1, Turin, Italy. [Sartori, D.] Osped Mirano, UOC Oncol & Ematol Oncol, Venice, Italy. [Falcone, A.] Univ Pisana, Azienda Osped, Dipartimento Oncol, Ist Toscano Tumori, Pisa, Italy. [Silvestris, N.] Ist Tumori Giovanni Paolo II, Dipartimento Oncol Med, Bari, Italy. [Beretta, G. D.] Osped Humanitas Gavazzeni, Oncol Med, Lombardia, Italy. [Buonadonna, A.] Ctr Riferimento Oncol, Aviano, Italy. [Sobrero, A.] Osped San Martino Genova, Div Oncol Med, Genoa, Italy. [Tamburini, E.] Osped Infermi, Rimini, Italy. [Amoroso, V.] Azienda Osped Spedali Civili Brescia, Oncol Med, Brescia, Italy. [Hsu, Y.] ImClone Syst LLC, Bridgewater, MA USA. [Chandrawansa, K.] Eli Lilly & Co, Bridgewater, MA USA. [Wilke, H.] Kliniken Essen Mitte Ctr Pallat Care, Essen, Germany. [Fuchs, C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Passalacqua, R.] Osped Cremona, Oncol Med, Cremona, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2015 VL 26 SU 6 MA L01 BP 90 EP 90 PG 1 WC Oncology SC Oncology GA CW7EA UT WOS:000365159600279 ER PT J AU Barone, C Brandi, G Daniele, B Villa, E Leo, S Di Fabio, F Aprile, G Colombo, M Sobrero, A Giannelli, G Porta, C Cabibbo, G Zhu, A Blanc, J Okusaka, T Chau, I Abada, P Yang, L Pastorelli, D AF Barone, C. Brandi, G. Daniele, B. Villa, E. Leo, S. Di Fabio, F. Aprile, G. Colombo, M. Sobrero, A. Giannelli, G. Porta, C. Cabibbo, G. Zhu, A. Blanc, J. Okusaka, T. Chau, I. Abada, P. Yang, L. Pastorelli, D. TI Ramucirumab (RAM) as Second-Line Treatment in Patients with Advanced Hepatocellular Carcinoma (HCC) Following First-Line Therapy with Sorafenib: Analyses from the Randomized Phase III REACH Study SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 17th National Congress of Medical Oncology CY OCT 23-25, 2015 CL Rome, ITALY C1 [Barone, C.] Policlin Univ A Gemelli, Rome, Italy. [Brandi, G.] Policlin St Orsola Malpighi, Bologna, Italy. [Daniele, B.] Azienda Osped G Rummo, Benevento, Italy. [Villa, E.] AO Policlin Modena, Modena, Italy. [Leo, S.] Osped Vito Fazzi, Lecce, Italy. [Di Fabio, F.] Azienda Osped Univ, Udine, Italy. [Colombo, M.] Osped Maggiore Policlin, Milan, Italy. [Sobrero, A.] Osped San Martino Genova, Genoa, Italy. [Giannelli, G.] Univ Bari Aldo Moro, Bari, Italy. [Porta, C.] Policlin San Matteo, I-27100 Pavia, Italy. [Cabibbo, G.] Azienda Osped Univ Policlin, Palermo, Italy. [Zhu, A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Blanc, J.] Hop St Andre, Bordeaux, France. [Okusaka, T.] Natl Canc Ctr, Tokyo, Japan. [Chau, I.] Royal Marsden Hosp, Sutton, Surrey, England. [Abada, P.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Yang, L.] ImClone Syst, Bridgewater, MA USA. [Pastorelli, D.] IRCCS, Ist Oncol Veneto, SSD Oncol Tumori Rari & Miscellanea, Padua, Italy. RI VILLA, ERICA/A-7576-2012 OI VILLA, ERICA/0000-0001-6388-7022 NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2015 VL 26 SU 6 MA L03 BP 91 EP 91 PG 1 WC Oncology SC Oncology GA CW7EA UT WOS:000365159600281 ER PT J AU Fumagalli, E Reichardt, P Kang, Y Blay, J Joensuu, H Schaefer, KB Kuss, I Kappeler, C Demetri, GD AF Fumagalli, E. Reichardt, P. Kang, Y. Blay, J. Joensuu, H. Schaefer, K. B. Kuss, I. Kappeler, C. Demetri, G. D. 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 ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 17th National Congress of Medical Oncology CY OCT 23-25, 2015 CL Rome, ITALY C1 [Fumagalli, E.] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Reichardt, P.] HELIOS Klinikum Berlin Buch, Berlin, Germany. [Kang, Y.] Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea. [Blay, J.] Ctr Leon Berard, F-69373 Lyon, France. [Joensuu, H.] Univ Helsinki, Cent Hosp, Comprehens Canc Ctr, Helsinki, Finland. [Schaefer, K. B.; Kuss, I.] Bayer Pharma AG, Berlin, Germany. [Kappeler, C.] Bayer HealthCare Pharmaceut, Berlin, Germany. [Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2015 VL 26 SU 6 MA L21 BP 97 EP 97 PG 1 WC Oncology SC Oncology GA CW7EA UT WOS:000365159600299 ER PT J AU Kimchi, EY Cash, SS AF Kimchi, Eyal Y. Cash, Sydney S. TI Seizures at the scale of individual neurons SO BRAIN LA English DT Editorial Material ID FOCAL EPILEPSY; HUMANS C1 [Kimchi, Eyal Y.; Cash, Sydney S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cash, SS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM scash@mgh.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD OCT 1 PY 2015 VL 138 BP 2807 EP 2808 DI 10.1093/brain/awv264 PN 10 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CW6VJ UT WOS:000365136200010 PM 26408654 ER PT J AU Hong, C Seo, H Kwak, M Jeon, J Jang, J Jeong, EM Myeong, J Hwang, YJ Ha, K Kang, MJ Lee, KP Yi, EC Kim, IG Jeon, JH Ryu, H So, I AF Hong, Chansik Seo, Hyemyung Kwak, Misun Jeon, Jeha Jang, Jihoon Jeong, Eui Man Myeong, Jongyun Hwang, Yu Jin Ha, Kotdaji Kang, Min Jueng Lee, Kyu Pil Yi, Eugene C. Kim, In-Gyu Jeon, Ju-Hong Ryu, Hoon So, Insuk TI Increased TRPC5 glutathionylation contributes to striatal neuron loss in Huntington's disease SO BRAIN LA English DT Article DE Ca2+; cysteine; GSSG; neurodegeneration; TRPC ID OXIDATIVE STRESS; CELL-DEATH; NEURODEGENERATIVE DISEASES; HYDROGEN-PEROXIDE; REDUCES TOXICITY; CHANNELS; RECEPTOR; CLEAVAGE; CALPAIN; SENSITIZATION AB Aberrant glutathione or Ca2+ homeostasis due to oxidative stress is associated with the pathogenesis of neurodegenerative disorders. The Ca2+-permeable transient receptor potential cation (TRPC) channel is predominantly expressed in the brain, which is sensitive to oxidative stress. However, the role of the TRPC channel in neurodegeneration is not known. Here, we report a mechanism of TRPC5 activation by oxidants and the effect of glutathionylated TRPC5 on striatal neurons in Huntington's disease. Intracellular oxidized glutathione leads to TRPC5 activation via TRPC5 S-glutathionylation at Cys176/Cys178 residues. The oxidized glutathione-activated TRPC5-like current results in a sustained increase in cytosolic Ca2+, activated calmodulin-dependent protein kinase and the calpain-caspase pathway, ultimately inducing striatal neuronal cell death. We observed an abnormal glutathione pool indicative of an oxidized state in the striatum of Huntington's disease transgenic (YAC128) mice. Increased levels of endogenous TRPC5 S-glutathionylation were observed in the striatum in both transgenic mice and patients with Huntington's disease. Both knockdown and inhibition of TRPC5 significantly attenuated oxidation-induced striatal neuronal cell death. Moreover, a TRPC5 blocker improved rearing behaviour in Huntington's disease transgenic mice and motor behavioural symptoms in littermate control mice by increasing striatal neuron survival. Notably, low levels of TRPC1 increased the formation of TRPC5 homotetramer, a highly Ca2+-permeable channel, and stimulated Ca2+-dependent apoptosis in Huntington's disease cells (STHdh(Q111/111)). Taken together, these novel findings indicate that increased TRPC5 S-glutathionylation by oxidative stress and decreased TRPC1 expression contribute to neuronal damage in the striatum and may underlie neurodegeneration in Huntington's disease. C1 [Hong, Chansik; Kwak, Misun; Myeong, Jongyun; Ha, Kotdaji; Jeon, Ju-Hong; So, Insuk] Seoul Natl Univ, Coll Med, Dept Physiol, Seoul 110799, South Korea. [Hong, Chansik; Kwak, Misun; Myeong, Jongyun; Ha, Kotdaji; Jeon, Ju-Hong; So, Insuk] Seoul Natl Univ, Coll Med, Inst Dermatol Sci, Seoul 110799, South Korea. [Seo, Hyemyung; Jeon, Jeha; Jang, Jihoon] Hanyang Univ, Dept Mol & Life Sci, Ansan 425791, South Korea. [Jeong, Eui Man; Kim, In-Gyu] Seoul Natl Univ, Dept Biochem & Mol Biol, Coll Med, Seoul 110799, South Korea. [Hwang, Yu Jin; Ryu, Hoon] VA Boston Healthcare Syst, Dept Neurol, Boston, MA 02118 USA. [Hwang, Yu Jin; Ryu, Hoon] Boston Univ, Alzheimers Dis Ctr, Sch Med, Boston, MA 02118 USA. [Kang, Min Jueng; Yi, Eugene C.] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Coll Med Pharm, Dept Mol Med & Biopharmaceut Sci, Seoul 110799, South Korea. [Lee, Kyu Pil] Chungnam Natl Univ, Dept Physiol, Coll Vet Med, Taejon 305764, South Korea. [Ryu, Hoon] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neuromed, Seoul 136791, South Korea. RP Ryu, H (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM hoonryu@bu.edu; insuk@snu.ac.kr FU National Research Foundation of Korea - Ministry of Science, ICT (Information & Communication Technology) and Future Planning (MSIP) of the Korean government [2010-0019472, 2012R1A2A1A01003073, 2011-0030049, 2011-0030928, 2012-003338, 2013R1A1A1010783]; NIH [NS067283]; KIST [2E24380]; Korea Health Technology R&D project through KHDI - Ministry of Health Welfare, ROK [HI14C1234]; BK21 plus program from the MSIP FX This study was supported by grants from the National Research Foundation of Korea, which is funded by the Ministry of Science, ICT (Information & Communication Technology) and Future Planning (MSIP) of the Korean government (2010-0019472 and 2012R1A2A1A01003073 to I.S., 2011-0030049, 2011-0030928, and 2012-003338 to H.S,, and 2013R1A1A1010783 to K. P. Lee), an NIH R01 grant (NS067283) and Flagship Grant of KIST (2E24380 to H.R.), and Korea Health Technology R&D project through KHDI, funded by the Ministry of Health & Welfare, ROK (HI14C1234 to E.C.Y.). C.H., M.K., and J.M. were supported by the BK21 plus program from the MSIP. NR 53 TC 9 Z9 9 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD OCT 1 PY 2015 VL 138 BP 3030 EP 3047 DI 10.1093/brain/awv188 PN 10 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CW6VJ UT WOS:000365136200028 PM 26133660 ER PT J AU Boes, AD Prasad, S Liu, HS Liu, Q Pascual-Leone, A Caviness, VS Fox, MD AF Boes, Aaron D. Prasad, Sashank Liu, Hesheng Liu, Qi Pascual-Leone, Alvaro Caviness, Verne S., Jr. Fox, Michael D. TI Network localization of neurological symptoms from focal brain lesions SO BRAIN LA English DT Article DE lesion network mapping; lesion networks; hallucination; central post-stroke pain; subcortical aphasia ID INTRINSIC FUNCTIONAL CONNECTIVITY; COMPLEX VISUAL HALLUCINATIONS; GLOBAL SIGNAL REGRESSION; CHARLES-BONNET-SYNDROME; RESTING-STATE NETWORKS; SUBCORTICAL APHASIA; NEUROPATHIC PAIN; SPATIAL NEGLECT; PEDUNCULAR HALLUCINOSIS; MECHANICAL ALLODYNIA AB A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had little overlap showed significant network overlap in cortical areas previously implicated in symptom expression (P < 10(-4)). These results suggest that (i) heterogeneous lesions producing similar symptoms share functional connectivity to specific brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique requires no specialized imaging of patients it may prove a versatile and broadly applicable approach for localizing neurological symptoms in the setting of brain lesions. C1 [Boes, Aaron D.; Pascual-Leone, Alvaro; Fox, Michael D.] Harvard Univ, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Div Cognit Neurol,Dept Neurol, Boston, MA 02215 USA. [Boes, Aaron D.; Pascual-Leone, Alvaro; Fox, Michael D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Boes, Aaron D.; Caviness, Verne S., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Paediat Neurol, Boston, MA 02114 USA. [Prasad, Sashank] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Div Neuroophthalmol, Boston, MA 02115 USA. [Liu, Hesheng; Liu, Qi; Fox, Michael D.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Liu, Qi] Beijing Normal Univ, Natl Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [Fox, Michael D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Boes, AD (reprint author), Harvard Univ, Sch Med, Dept Neurol, Div Cognit Neurol, 330 Brookline Ave, Boston, MA 02215 USA. EM aboes@partners.org; foxmdphd@gmail.com FU National Institute of Health \ National Institute of Neurologial Disorders and Stroke [5R25NS065743-05, K25NS069805, R25NS065743, K23NS083741]; Sidney R. Baer, Jr Foundation; Brain & Behavior Research Foundation NARSAD Young Investigator grant; American Brain Foundation; National Institute of Health \ National Center for Research Resources: Harvard Clinical and Translational Science Center [UL1 RR025758]; National Institute of Health \ National Institute on Aging [P01AG036694] FX A.D.B. was supported by National Institute of Health \ National Institute of Neurologial Disorders and Stroke (Grant number 5R25NS065743-05) and the Sidney R. Baer, Jr Foundation. H.L. was supported by National Institute of Health \ National Institute of Neurologial Disorders and Stroke (Grant number K25NS069805) and the Brain & Behavior Research Foundation NARSAD Young Investigator grant. M.D.F. was supported by National Institute of Health \ National Institute of Neurologial Disorders and Stroke (Grant numbers R25NS065743, K23NS083741), and the American Brain Foundation. Work on this study was also supported by grants from the National Institute of Health \ National Center for Research Resources: Harvard Clinical and Translational Science Center (Grant number UL1 RR025758). The National Institute of Health \ National Institute on Aging funded the data collection for the older cohort used in this study (Harvard Aging Brain Study, Grant number P01AG036694). NR 91 TC 7 Z9 7 U1 4 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD OCT 1 PY 2015 VL 138 BP 3061 EP 3075 DI 10.1093/brain/awv228 PN 10 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CW6VJ UT WOS:000365136200030 PM 26264514 ER PT J AU Munshi, MN Segal, AR Slyne, C Samur, AA Brooks, KM Horton, ES AF Munshi, M. N. Segal, A. R. Slyne, C. Samur, A. A. Brooks, K. M. Horton, E. S. TI Shortfalls of the use of HbA1C-derived eAG in older adults with diabetes SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Diabetes; Older adults; HbA1c; Estimated average glucose (eAG) ID GLUCOSE VARIABILITY; HEMOGLOBIN A(1C); GLYCEMIC VARIABILITY; COMPLICATIONS; HBA1C; A1C; HYPOGLYCEMIA; MELLITUS; DISEASE; ASSAY AB Aims: The hemoglobin HbA1C (HbA1C) value, translated into estimated average glucose concentration (eAG), is commonly used to assess glycaemic control and manage treatment regimens in people with diabetes. However, the relationships among HbA1C-derived eAG, and mean glucose concentration derived from continuous glucose monitoring (CGM) in different populations have not been well studied. We examined this relationship in older people with diabetes and compared the results to those currently used in clinical practice. Methods: Data from three studies evaluating CGM in older adults (>= 70 years of age), with stable glycaemic control were analyzed retrospectively. Mean glucose and mean amplitude of glucose excursion (MAGE) were calculated from CGM data and correlated with HbA1C and HbA1C-derived eAG using the ADAG study formula. Results: HbA1C and CGM data were analyzed from 90 patients with mean age 76 +/- 5 years, HbA1C 7.9 +/- 1.2% (63 +/- 13 mmol/mol) and 77% with Type 2 diabetes. The HbA1C and HbA1C-derived eAG correlated significantly with CGM-measured mean glucose (r(2) = 0.30, p < 0.0001) and MAGE (r(2) = 0.16, p = 0.00013) in this population and all its subgroups, but the slopes of the relationship between HbA1C and eAG or CGM-measured mean glucose were significantly different. Conclusions: HbA1C-derived eAG values may not accurately reflect CGM-measured mean glucose or MAGE in older adults with diabetes. Wide glucose excursions should be considered and HbA1C should be interpreted cautiously when making treatment changes based on HbA1C. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Munshi, M. N.; Segal, A. R.; Slyne, C.; Horton, E. S.] Joslin Diabet Ctr, Boston, MA USA. [Munshi, M. N.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Munshi, M. N.; Horton, E. S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Segal, A. R.] MCPHS Univ, Boston, MA USA. [Samur, A. A.] Akdeniz Univ, Antalya, Turkey. [Brooks, K. M.] Tufts Univ, Sch Med, Medford, MA USA. RP Munshi, MN (reprint author), 110 Francis St,LMOB 1B, Boston, MA 02215 USA. EM medha.munshi@joslin.harvard.edu NR 28 TC 6 Z9 6 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 EI 1872-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD OCT PY 2015 VL 110 IS 1 BP 60 EP 65 DI 10.1016/j.diabres.2015.07.012 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW6IJ UT WOS:000365100800011 PM 26272739 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Another step toward personalized care of patients with heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Editorial Material ID PRESERVED EJECTION FRACTION; NATRIURETIC PEPTIDE; TROPONIN-T; BIOMARKERS; PHENOTYPES; MORTALITY; RISK C1 Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 19 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD OCT PY 2015 VL 17 IS 10 BP 988 EP 990 DI 10.1002/ejhf.348 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV9ZZ UT WOS:000364649800002 PM 26377433 ER PT J AU Zile, MR Abraham, WT Weaver, FA Butter, C Ducharme, A Halbach, M Klug, D Lovett, EG Muller-Ehmsen, J Schafer, JE Senni, M Swarup, V Wachter, R Little, WC AF Zile, Michael R. Abraham, William T. Weaver, Fred A. Butter, Christian Ducharme, Anique Halbach, Marcel Klug, Didier Lovett, Eric G. Mueller-Ehmsen, Jochen Schafer, Jill E. Senni, Michele Swarup, Vijay Wachter, Rolf Little, William C. TI Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Baroreflex; Heart failure; Resynchronization; Autonomic nervous system; Randomized controlled trial ID PROGNOSTIC IMPLICATIONS; ARTERIAL BAROREFLEX; FAILING HEART; HF TRIAL; INHIBITION; METOPROLOL; SYSTEM AB AimsIncreased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Carotid baroreceptor stimulation (baroreflex activation therapy, BAT) results in centrally mediated reduction of sympathetic and increase in parasympathetic activity. Because patients treated with cardiac resynchronization therapy (CRT) may have less sympathetic/parasympathetic imbalance, we hypothesized that there would be differences in the response to BAT in patients with CRT vs. those without CRT. Methods and resultsNew York Heart Association (NYHA) Class III patients with an ejection fraction (EF) 35% were randomized (1 : 1) to ongoing guideline-directed medical and device therapy (GDMT, control) or ongoing GDMT plus BAT. Safety endpoint was system-/procedure-related major adverse neurological and cardiovascular events (MANCE). Efficacy endpoints were Minnesota Living with Heart Failure Quality of Life (QoL), 6-min hall walk distance (6MHWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and HF hospitalization rate. In this sample, 146 patients were randomized (70 control; 76 BAT) and were 140 activated (45 with CRT and 95 without CRT). MANCE-free rate at 6 months was 100% in CRT and 96% in no-CRT group. At 6 months, in the no-CRT group, QoL score, 6MHWD, LVEF, NT-proBNP and HF hospitalizations were significantly improved in BAT patients compared with controls. Changes in efficacy endpoints in the CRT group favoured BAT; however, the improvements were less than in the no-CRT group and were not statistically different from control. ConclusionsBAT is safe and significantly improved QoL, exercise capacity, NTpro-BNP, EF, and rate of HF hospitalizations in GDMT-treated NYHA Class III HF patients. These effects were most pronounced in patients not treated with CRT. C1 [Zile, Michael R.] Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Zile, Michael R.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. [Abraham, William T.] Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA. [Weaver, Fred A.] Univ So Calif, Keck Sch Med, Div Vasc Surg & Endovasc Therapy, Los Angeles, CA 90033 USA. [Butter, Christian] Immanuel Heart Ctr Bernau, Med Sch Brandenburg, Dept Cardiol, Bernau, Germany. [Ducharme, Anique] Univ Montreal, Montreal Heart Inst, Montreal, PQ H3C 3J7, Canada. [Halbach, Marcel] Univ Hosp Cologne, Dept Internal Med 3, Cologne, Germany. [Klug, Didier] Univ Hosp, Dept Cardiol A, Lille, France. [Lovett, Eric G.] CVRx Inc, Dept Res, Minneapolis, MN USA. [Mueller-Ehmsen, Jochen] Asklepios Klin Altona, Dept Med, Hamburg, Germany. [Schafer, Jill E.] NAMSA Inc, Dept Stat, Minneapolis, MN USA. [Senni, Michele] Osped Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy. [Swarup, Vijay] Arizona Heart Hosp, Dept Electrophysiol, Phoenix, AZ USA. [Wachter, Rolf] Univ Med Gottingen, Clin Cardiol & Pneumol, Gottingen, Germany. [Wachter, Rolf] German Cardiovasc Res Ctr DZHK, Gottingen, Germany. [Little, William C.] Univ Mississippi, Div Cardiovasc, Med Ctr, Jackson, MS 39216 USA. RP Zile, MR (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, 114 Doughty St,Thurmond Gazes 323, Charleston, SC 29425 USA. EM zilem@musc.edu OI Wachter, Rolf/0000-0003-2231-2200 FU CVRx, Inc., Minneapolis, MN, USA FX This study was funded by CVRx, Inc., Minneapolis, MN, USA. NR 26 TC 9 Z9 9 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD OCT PY 2015 VL 17 IS 10 BP 1066 EP 1074 DI 10.1002/ejhf.299 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV9ZZ UT WOS:000364649800015 PM 26011593 ER PT J AU Ananthakrishnan, AN Lieberman, D AF Ananthakrishnan, Ashwin N. Lieberman, David TI Patient Electronic Health Records as a Means to Approach Genetic Research in Gastroenterology SO GASTROENTEROLOGY LA English DT Editorial Material DE Electronic Health Records; Genetics; Informatics; Natural Language Processing ID INFLAMMATORY-BOWEL-DISEASE; RHEUMATOID-ARTHRITIS; COLORECTAL-CANCER; MEDICAL-RECORDS; FAMILY-HISTORY; RISK AB Electronic health records (EHRs) are being increasingly utilized and form a unique source of extensive data gathered during routine clinical care. Through use of codified and free text concepts identified using clinical informatics tools, disease labels can be assigned with a high degree of accuracy. Analysis linking such EHR-assigned disease labels to a biospecimen repository has demonstrated that genetic associations identified in prospective cohorts can be replicated with adequate statistical power and novel phenotypic associations identified. In addition, genetic discovery research can be performed utilizing clinical, laboratory, and procedure data obtained during care. Challenges with such research include the need to tackle variability in quality and quantity of EHR data and importance of maintaining patient privacy and data security. With appropriate safeguards, this novel and emerging field of research offers considerable promise and potential to further scientific research in gastroenterology efficiently, cost-effectively, and with engagement of patients and communities. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [Lieberman, David] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU NIDDK NIH HHS [K23 DK097142, P30 DK043351] NR 18 TC 1 Z9 1 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 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2015 VL 149 IS 5 BP 1134 EP 1137 DI 10.1053/j.gastro.2015.06.005 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CW6DM UT WOS:000365087700002 PM 26073373 ER PT J AU Henry, SG Czarnecki, D Kahn, VC Chou, WYS Fagerlin, A Ubel, PA Rovner, DR Alexander, SC Knight, SJ Holmes-Rovner, M AF Henry, Stephen G. Czarnecki, Danielle Kahn, Valerie C. Chou, Wen-Ying Sylvia Fagerlin, Angela Ubel, Peter A. Rovner, David R. Alexander, Stewart C. Knight, Sara J. Holmes-Rovner, Margaret TI Patient-physician communication about early stage prostate cancer: analysis of overall visit structure SO HEALTH EXPECTATIONS LA English DT Article DE discourse analysis; patient-centred communication; prostate cancer; qualitative research; structure; transitions; veterans ID MEDICAL ENCOUNTERS; DECISION-MAKING; BAD-NEWS; TRANSITIONS; PARTICIPATION; DISCOURSE; SKILLS; MEN AB Background We know little about patient-physician communication during visits to discuss diagnosis and treatment of prostate cancer. Objective To examine the overall visit structure and how patients and physicians transition between communication activities during visits in which patients received new prostate cancer diagnoses. Participants Forty veterans and 18 urologists at one VA medical centre. Methods We coded 40 transcripts to identify major communication activities during visits and used empiric discourse analysis to analyse transitions between activities. Results We identified five communication activities that occurred in the following typical sequence: 'diagnosis delivery', 'risk classification', 'options talk', 'decision talk' and 'next steps'. The first two activities were typically brief and involved minimal patient participation. Options talk was typically the longest activity; physicians explicitly announced the beginning of options talk and framed it as their professional responsibility. Some patients were unsure of the purpose of visit and/or who should make treatment decisions. Conclusion Visits to deliver the diagnosis of early stage prostate cancer follow a regular sequence of communication activities. Physicians focus on discussing treatment options and devote comparatively little time and attention to discussing the new cancer diagnosis. Towards the goal of promoting patient-centred communication, physicians should consider eliciting patient reactions after diagnosis delivery and explaining the decision-making process before describing treatment options. C1 [Henry, Stephen G.] Univ Calif Davis, Div Gen Med Geriatr & Bioeth, Sacramento, CA 95817 USA. [Czarnecki, Danielle] Univ Michigan, Dept Sociol, Ann Arbor, MI 48109 USA. [Kahn, Valerie C.; Fagerlin, Angela] Univ Michigan, Ctr Bioeth & Social Sci Med, Ann Arbor, MI 48109 USA. [Chou, Wen-Ying Sylvia] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Fagerlin, Angela] Ann Arbor VA HSR&D Ctr Clin Management Res, Ann Arbor, MI USA. [Fagerlin, Angela] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Fagerlin, Angela] Univ Michigan, Dept Psychol, Ann Arbor, MI USA. [Ubel, Peter A.] Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA. [Rovner, David R.] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Alexander, Stewart C.] Duke Univ, Dept Med, Durham, NC USA. [Alexander, Stewart C.] Durham VA Med Ctr, Durham, NC USA. [Knight, Sara J.] Vet Hlth Adm, Off Res & Dev, VA Hlth Serv Res & Dev, Washington, DC USA. [Knight, Sara J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Holmes-Rovner, Margaret] Michigan State Univ, Ctr Eth & Humanities Life Sci, E Lansing, MI 48824 USA. RP Henry, SG (reprint author), Univ Calif Davis, Div Gen Med Geriatr & Bioeth, 4150 5 St Suite 2400, Sacramento, CA 95817 USA. EM sghenry@ucdavis.edu FU Blue Cross Blue Shield of Michigan Foundation (Detroit, MI) [1722.II]; University of Michigan Robert Wood Johnson Foundation Health and Society Scholars program; IIR Merit Award from the U.S. Department of Veterans Affairs (Washington, DC) [IIR 05-283] FX This study was supported in part by grants from the Blue Cross Blue Shield of Michigan Foundation (1722.II; Detroit, MI) and the University of Michigan Robert Wood Johnson Foundation Health and Society Scholars program (Ann Arbor, MI) to Dr. Henry. The parent study was funded by an IIR Merit Award from the U.S. Department of Veterans Affairs (IIR 05-283, Washington, DC) to Dr. Fagerlin. NR 36 TC 2 Z9 2 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-6513 EI 1369-7625 J9 HEALTH EXPECT JI Health Expect. PD OCT PY 2015 VL 18 IS 5 BP 1757 EP 1768 DI 10.1111/hex.12168 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CW5OU UT WOS:000365046700093 PM 24372758 ER PT J AU Lau, KM Parikh, M Harvey, DJ Huang, CJ Farias, ST AF Lau, Karen M. Parikh, Mili Harvey, Danielle J. Huang, Chun-Jung Farias, Sarah Tomaszewski TI Early Cognitively Based Functional Limitations Predict Loss of Independence in Instrumental Activities of Daily Living in Older Adults SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Alzheimer's disease; Dementia; Everyday function; Instrumental activities of daily living; Cognition; Disability ID DATA SET UDS; ALZHEIMERS-DISEASE; DISABLEMENT PROCESS; NEUROPSYCHOLOGICAL TESTS; EVERYDAY COGNITION; ECOLOGICAL VALIDITY; CAREGIVER BURDEN; MILD DEMENTIA; IMPAIRMENT; DISABILITY AB Older adults with early forms of neurodegenerative disease are at risk for functional disability, which is often defined by the loss of independence in instrumental activities of daily living (IADLs). The current study investigated the influence of mild changes in everyday functional abilities (referred to as functional limitations) on risk for development of incident functional disability. A total of 407 participants, who were considered cognitively normal or diagnosed with mild cognitive impairment (MCI) at baseline, were followed longitudinally over an average 4.1 years (range=0.8-9.2 years). Informant-based ratings from the Everyday Cognition (ECog; Farias et al., 2008) and the Instrumental Activities of Daily Living (Lawton & Brody, 1969) scales assessed the degree of functional limitations and incident IADL disability, respectively. Cox proportional hazards models revealed that more severe functional limitations (as measured by the Total ECog score) at baseline were associated with approximately a four-fold increased risk of developing IADL disability a few years later. Among the ECog domains, functional limitations in Everyday Planning, Everyday Memory, and Everyday Visuospatial domains were associated with the greatest risk of incident functional disability. These results remained robust even after controlling for participants' neuropsychological functioning on tests of executive functions and episodic memory. Current findings indicate that early functional limitations have prognostic value in identifying older adults at risk for developing functional disability. Findings highlight the importance of developing interventions to support everyday abilities related to memory, executive function, and visuospatial skills in an effort to delay loss of independence in IADLs. C1 [Lau, Karen M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lau, Karen M.; Farias, Sarah Tomaszewski] Univ Calif Davis, Sch Med, Dept Neurol, Sacramento, CA 95817 USA. [Parikh, Mili] Vet Affairs Northern Calif Hlth Care Syst, Mather, CA USA. [Harvey, Danielle J.; Huang, Chun-Jung] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Div Biostat, Sacramento, CA 95817 USA. RP Farias, ST (reprint author), Univ Calif Davis, Sch Med, Dept Neurol, 4860 Y St,Suite 3700, Sacramento, CA 95817 USA. EM sarah.farias@ucdmc.ucdavis.edu FU National Institute on Aging [AG031252, AG10129] FX This study was supported by the following grants from the National Institute on Aging (grant numbers: AG031252 and AG10129). The authors have no conflicts of interest to report. No competing financial interests exist. NR 78 TC 0 Z9 0 U1 6 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD OCT PY 2015 VL 21 IS 9 SI SI BP 688 EP 698 DI 10.1017/S1355617715000818 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA CW4JT UT WOS:000364958300004 PM 26391766 ER PT J AU Bizet, AA Becker-Heck, A Ryan, R Weber, K Filhol, E Krug, P Halbritter, J Delous, M Lasbennes, MC Linghu, B Oakeley, EJ Zarhrate, M Nitschke, P Garfa-Traore, M Serluca, F Yang, F Bouwmeester, T Pinson, L Cassuto, E Dubot, P Elshakhs, NAS Sahel, JA Salomon, R Drummond, IA Gubler, MC Antignac, C Chibout, S Szustakowski, JD Hildebrandt, F Lorentzen, E Sailer, AW Benmerah, A Saint-Mezard, P Saunier, S AF Bizet, Albane A. Becker-Heck, Anita Ryan, Rebecca Weber, Kristina Filhol, Emilie Krug, Pauline Halbritter, Jan Delous, Marion Lasbennes, Marie-Christine Linghu, Bolan Oakeley, Edward J. Zarhrate, Mohammed Nitschke, Patrick Garfa-Traore, Meriem Serluca, Fabrizio Yang, Fan Bouwmeester, Tewis Pinson, Lucile Cassuto, Elisabeth Dubot, Philippe Elshakhs, Neveen A. Soliman Sahel, Jose A. Salomon, Remi Drummond, Iain A. Gubler, Marie-Claire Antignac, Corinne Chibout, Salandine Szustakowski, Joseph D. Hildebrandt, Friedhelm Lorentzen, Esben Sailer, Andreas W. Benmerah, Alexandre Saint-Mezard, Pierre Saunier, Sophie TI Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization SO NATURE COMMUNICATIONS LA English DT Article ID MULTIPOINT LINKAGE ANALYSIS; CILIOGENESIS; DEFECTS; CILIARY; COMPLEX; CELLS; NEPHRONOPHTHISIS; CILIOPATHY; TRANSPORT; POLARITY AB Ciliopathies are a large group of clinically and genetically heterogeneous disorders caused by defects in primary cilia. Here we identified mutations in TRAF3IP1 (TNF Receptor-Associated Factor Interacting Protein 1) in eight patients from five families with nephronophthisis (NPH) and retinal degeneration, two of the most common manifestations of ciliopathies. TRAF3IP1 encodes IFT54, a subunit of the IFT-B complex required for ciliogenesis. The identified mutations result in mild ciliary defects in patients but also reveal an unexpected role of IFT54 as a negative regulator of microtubule stability via MAP4 (microtubule-associated protein 4). Microtubule defects are associated with altered epithelialization/polarity in renal cells and with pronephric cysts and microphthalmia in zebrafish embryos. Our findings highlight the regulation of cytoplasmic microtubule dynamics as a role of the IFT54 protein beyond the cilium, contributing to the development of NPH-related ciliopathies. C1 [Bizet, Albane A.; Ryan, Rebecca; Filhol, Emilie; Krug, Pauline; Delous, Marion; Salomon, Remi; Gubler, Marie-Claire; Antignac, Corinne; Benmerah, Alexandre; Saunier, Sophie] Inserm UMR 1163, Lab Hereditary Kidney Dis, F-75015 Paris, France. [Bizet, Albane A.; Ryan, Rebecca; Filhol, Emilie; Krug, Pauline; Delous, Marion; Zarhrate, Mohammed; Nitschke, Patrick; Salomon, Remi; Gubler, Marie-Claire; Antignac, Corinne; Benmerah, Alexandre; Saunier, Sophie] Paris Descartes Sorbonne Paris Cite Univ, Imagine Inst, F-75015 Paris, France. [Weber, Kristina; Lorentzen, Esben] Max Planck Inst Biochem, Dept Struct Cell Biol, D-82152 Martinsried, Germany. [Halbritter, Jan; Hildebrandt, Friedhelm] Boston Childrens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. [Halbritter, Jan; Hildebrandt, Friedhelm] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Halbritter, Jan] Univ Clin Leipzig, Dept Internal Med, Div Nephrol, D-04103 Leipzig, Germany. [Linghu, Bolan; Serluca, Fabrizio; Yang, Fan; Szustakowski, Joseph D.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Zarhrate, Mohammed] Inserm UMR 1163, Genom Core Facil, F-75015 Paris, France. [Nitschke, Patrick] Paris Descartes Sorbonne Paris Cite Univ, Bioinformat Core Facil, F-75015 Paris, France. [Garfa-Traore, Meriem] Paris Descartes Sorbonne Paris Cite Univ, Cell Imaging Platform, INSERM Struct Federat Rech Necker US24, F-75015 Paris, France. [Pinson, Lucile] Arnaud de Villeneuve Univ Hlth Ctr, Dept Med Genet, F-34090 Montpellier, France. [Cassuto, Elisabeth] Univ Nice, Ctr Hlth, LArchet Hosp 2, Dept Nephrol, F-06202 Nice, France. [Dubot, Philippe] William Morey Hosp, Hemodialysis Nephrol Dept, F-71321 Chalon Sur Saone, France. [Elshakhs, Neveen A. Soliman] Cairo Univ, Egyptian Grp Orphan Renal Dis, Dept Pediat, Ctr Pediat Nephrol & Transplantat, Cairo 11956, Egypt. [Sahel, Jose A.] Univ Paris 06, INSERM U968, CNRS UMR 7210, Sorbonne Univ,UMR S968,Inst Vis, F-75012 Paris, France. [Sahel, Jose A.] Ctr Hosp Natl Ophtalmol Quinze Vingts, INSERM, Direct Hosp & Org Soins, Ctr Invest Clin 1423, F-75012 Paris, France. [Salomon, Remi] Necker Enfants Malad Hosp, AP HP, Pediat Nephrol Dept, F-75015 Paris, France. [Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02114 USA. [Drummond, Iain A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Antignac, Corinne] Necker Enfants Malad Hosp, AP HP, Dept Genet, F-75015 Paris, France. RP Saint-Mezard, P (reprint author), Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. EM pierre.saint-mezard@novartis.com; sophie.saunier@inserm.fr RI Sahel, Jose-Alain/F-3172-2017; OI Lorentzen, Esben/0000-0001-6493-7220; Sailer, Andreas/0000-0002-9015-7946 FU 'Agence Nationale de la Recherche' (ANR) [20100BLAN112202]; investments for the future program [ANR-10-IAHY-01]; Fondation pour la Recherche Medicale [DEQ20130326532]; NIH [DK068306]; [DEA20120624188] FX We are grateful to the patients and their families for their participation. We thank J. Malicki for providing us with the elipsa zebrafish, G. Pazour, J. Nelson, L. Pedersen and R. Koster for giving us the Flag-MmIFT54, GFP-MAP4 and EB3-GFP constructs, respectively. We greatly acknowledge N. Goudin (Necker cell imaging facility) for providing expert knowledge on confocal microscopy, E. Weyher-Stingl (core facility, MPI of Biochemistry) for assistance with the circular dichroism measurements, H. Voshol for support in mass spectrometry and J. Duca for help in molecular modelling, C. Bole-Feysot, O. Alibeu, S. Pruvost and M. Parisot (Imagine Genomic plateform) and the Necker Bioinformatic facility. We thank S. Berissi (Histology facility), G. Pivert (Pathology department, Necker hospital), O. Pelle (Cell sorting facility), S. Laurent and N. Stemler (Cellular Biology, NIBR), for their excellent technical assistance. The authors are grateful to the following scientists for their support: L. Klickstein, M. Labow, M. Schebesta, and K. Johnson for providing intellectual input at various stages of the project. Finally, We thank S. Helliwell and S. Kirkland for their precious help in manuscript correction. This work was supported by grants from the 'Agence Nationale de la Recherche' (ANR) to S. S. (20100BLAN112202) and investments for the future program-ANR-10-IAHY-01 to S. S., the Fondation pour la Recherche Medicale (DEQ20130326532 to SS and RR) and (DEA20120624188 to P.K.) and the Fondation ARC (EML20110602384) for the purchase of the LEICA SP8 confocal microscope. This research was supported by a grant from the NIH to F.H. (DK068306). F.H. is an Investigator of the Howard Hughes Medical Institute and Warren E. Grupe Professor of Pediatrics at the Harvard Medical School. NR 52 TC 14 Z9 18 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2015 VL 6 AR 8666 DI 10.1038/ncomms9666 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW4BN UT WOS:000364936200008 PM 26487268 ER PT J AU Thoonen, R Cauwels, A Decaluwe, K Geschka, S Tainsh, RE Delanghe, J Hochepied, T De Cauwer, L Rogge, E Voet, S Sips, P Karas, RH Bloch, KD Vuylsteke, M Stasch, JP Van de Voorde, J Buys, ES Brouckaert, P AF Thoonen, Robrecht Cauwels, Anje Decaluwe, Kelly Geschka, Sandra Tainsh, Robert E. Delanghe, Joris Hochepied, Tino De Cauwer, Lode Rogge, Elke Voet, Sofie Sips, Patrick Karas, Richard H. Bloch, Kenneth D. Vuylsteke, Marnik Stasch, Johannes-Peter Van de Voorde, Johan Buys, Emmanuel S. Brouckaert, Peter TI Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice SO NATURE COMMUNICATIONS LA English DT Article ID NITRIC-OXIDE SYNTHASE; SEPTIC SHOCK; METHYLENE-BLUE; BLOOD-PRESSURE; HEART-FAILURE; SEVERE SEPSIS; KINASE-I; CGMP; ACTIVATION; IDENTIFICATION AB Oxidative stress, a central mediator of cardiovascular disease, results in loss of the prosthetic haem group of soluble guanylate cyclase (sGC), preventing its activation by nitric oxide (NO). Here we introduce Apo-sGC mice expressing haem-free sGC. Apo-sGC mice are viable and develop hypertension. The haemodynamic effects of NO are abolished, but those of the sGC activator cinaciguat are enhanced in apo-sGC mice, suggesting that the effects of NO on smooth muscle relaxation, blood pressure regulation and inhibition of platelet aggregation require sGC activation by NO. Tumour necrosis factor (TNF)-induced hypotension and mortality are preserved in apo-sGC mice, indicating that pathways other than sGC signalling mediate the cardiovascular collapse in shock. Apo-sGC mice allow for differentiation between sGC-dependent and -independent NO effects and between haem-dependent and -independent sGC effects. Apo-sGC mice represent a unique experimental platform to study the in vivo consequences of sGC oxidation and the therapeutic potential of sGC activators. C1 [Thoonen, Robrecht; Cauwels, Anje; Hochepied, Tino; De Cauwer, Lode; Rogge, Elke; Voet, Sofie; Sips, Patrick; Brouckaert, Peter] Univ Ghent VIB, Lab Mol Pathol & Expt Therapy, Inflammat Res Ctr, B-9052 Ghent, Belgium. [Thoonen, Robrecht; Cauwels, Anje; Hochepied, Tino; De Cauwer, Lode; Rogge, Elke; Voet, Sofie; Sips, Patrick; Brouckaert, Peter] Univ Ghent, Dept Biomed Mol Biol, B-9052 Ghent, Belgium. [Decaluwe, Kelly; Van de Voorde, Johan] Univ Ghent, Dept Pharmacol, B-9000 Ghent, Belgium. [Geschka, Sandra; Stasch, Johannes-Peter] Bayer Pharma AG, Cardiovasc Res, D-42096 Wuppertal, Germany. [Tainsh, Robert E.; Bloch, Kenneth D.; Buys, Emmanuel S.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Res Inst, Boston, MA 02114 USA. [Delanghe, Joris] Ghent Univ Hosp, Dept Biol Clin, B-9000 Ghent, Belgium. [Karas, Richard H.] Tufts Med Ctr, Mol Cardiol Res Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. [Vuylsteke, Marnik] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium. [Vuylsteke, Marnik] Univ Ghent, Dept Plant Biotechnol & Genet, B-9052 Ghent, Belgium. [Stasch, Johannes-Peter] Univ Halle Wittenberg, Sch Pharm, Dept Pharmacol, D-06108 Halle, Germany. RP Brouckaert, P (reprint author), Univ Ghent VIB, Lab Mol Pathol & Expt Therapy, Inflammat Res Ctr, B-9052 Ghent, Belgium. EM robrecht.thoonen@gmail.com; peter.brouckaert@UGent.be OI Sips, Patrick/0000-0001-9241-5980 FU BOF-GOA; FWO Vlaanderen; AHA; Harvard Medical School; NIH [R01EY022746-01] FX We thank the animal caretakers from the DMBR, VIB for animal care and breeding, and Dr M. Mendelsohn for reviewing the manuscript. Research was supported by BOF-GOA and FWO Vlaanderen (PB, JVDV), Scientist Development Grant from the AHA (ESB), Eleanor and Miles Shore 50th Anniversary Fellowship for Scholars in Medicine from Harvard Medical School (ESB) and by NIH R01EY022746-01 (ESB). NR 60 TC 11 Z9 11 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2015 VL 6 AR 8482 DI 10.1038/ncomms9482 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW3YC UT WOS:000364927300001 PM 26442659 ER PT J AU Yuzugullu, H Baitsch, L Von, T Steiner, A Tong, HX Ni, J Clayton, LK Bronson, R Roberts, TM Gritsman, K Zhao, JJ AF Yuzugullu, Haluk Baitsch, Lukas Thanh Von Steiner, Allison Tong, Haoxuan Ni, Jing Clayton, Linda K. Bronson, Roderick Roberts, Thomas M. Gritsman, Kira Zhao, Jean J. TI A PI3K p110 beta-Rac signalling loop mediates Pten-loss-induced perturbation of haematopoiesis and leukaemogenesis SO NATURE COMMUNICATIONS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; PHOSPHOINOSITIDE 3-KINASE; STEM-CELLS; GUANOSINE TRIPHOSPHATASES; TUMOR-SUPPRESSOR; DIVERGENT ROLES; ISOFORMS; RAC; P110-ALPHA; P110-DELTA AB The tumour suppressor PTEN, which antagonizes PI3K signalling, is frequently inactivated in haematologic malignancies. In mice, deletion of PTEN in haematopoietic stem cells (HSCs) causes perturbed haematopoiesis, myeloproliferative neoplasia (MPN) and leukaemia. Although the roles of the PI3K isoforms have been studied in PTEN-deficient tumours, their individual roles in PTEN-deficient HSCs are unknown. Here we show that when we delete PTEN in HSCs using the Mx1-Cre system, p110 beta ablation prevents MPN, improves HSC function and suppresses leukaemia initiation. Pharmacologic inhibition of p110 beta in PTEN-deficient mice recapitulates these genetic findings, but suggests involvement of both Akt-dependent and -independent pathways. Further investigation reveals that a p110 beta-Rac signalling loop plays a critical role in PTEN-deficient HSCs. Together, these data suggest that myeloid neoplasia driven by PTEN loss is dependent on p110 beta via p110 beta-Rac-positive-feedback loop, and that disruption of this loop may offer a new and effective therapeutic strategy for PTEN-deficient leukaemia. C1 [Yuzugullu, Haluk; Baitsch, Lukas; Thanh Von; Steiner, Allison; Tong, Haoxuan; Ni, Jing; Clayton, Linda K.; Roberts, Thomas M.; Gritsman, Kira; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Yuzugullu, Haluk; Baitsch, Lukas; Thanh Von; Tong, Haoxuan; Ni, Jing; Roberts, Thomas M.; Gritsman, Kira; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Bronson, Roderick] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr Rodent Histopathol C, Boston, MA 02215 USA. RP Roberts, TM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM Thomas_roberts@dfci.harvard.edu; kira.gritsman@einstein.yu.edu; jean_zhao@dfci.harvard.edu FU Swiss National Science Foundation (FNSNF) [PBLA03-140100]; Leukemia & Lymphoma Society (LLS) [5408-13]; NIH [5K08CA149208, CA172461, CA187918] FX We thank Drs E. Weisberg, Jhaveri-Schneider and Omer Yilmaz for scientific discussions and critical reading. We thank Dr J. Ihle (St. Jude Children's Research Hospital) for providing the p110 delta KO mice. This work was supported by the Swiss National Science Foundation (FNSNF #PBLA03-140100 to L.B.) and the Leukemia & Lymphoma Society (LLS #5408-13 to L.B.), and NIH grants 5K08CA149208 (K.G.), CA172461 (J.J.Z.) and CA187918 (T.M.R. and J.J.Z.). NR 56 TC 3 Z9 3 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2015 VL 6 AR 8501 DI 10.1038/ncomms9501 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW3YT UT WOS:000364929000003 PM 26442967 ER PT J AU Ramkissoon, SH Bi, WL Schumacher, SE Ramkissoon, LA Haidar, S Knoff, D Dubuc, A Brown, L Burns, M Cryan, JB Abedalthagafi, M Kang, YJ Schultz, N Reardon, DA Lee, EQ Rinne, ML Norden, AD Nayak, L Ruland, S Doherty, LM LaFrankie, DC Horvath, M Aizer, AA Russo, A Arvold, ND Claus, EB Al-Mefty, O Johnson, MD Golby, AJ Dunn, IF Chiocca, EA Trippa, L Santagata, S Folkerth, RD Kantoff, P Rollins, BJ Lindeman, NI Wen, PY Ligon, AH Beroukhim, R Alexander, BM Ligon, KL AF Ramkissoon, Shakti H. Bi, Wenya Linda Schumacher, Steven E. Ramkissoon, Lori A. Haidar, Sam Knoff, David Dubuc, Adrian Brown, Loreal Burns, Margot Cryan, Jane B. Abedalthagafi, Malak Kang, Yun Jee Schultz, Nikolaus Reardon, David A. Lee, Eudocia Q. Rinne, Mikael L. Norden, Andrew D. Nayak, Lakshmi Ruland, Sandra Doherty, Lisa M. LaFrankie, Debra C. Horvath, Margaret Aizer, Ayal A. Russo, Andrea Arvold, Nils D. Claus, Elizabeth B. Al-Mefty, Ossama Johnson, Mark D. Golby, Alexandra J. Dunn, Ian F. Chiocca, E. Antonio Trippa, Lorenzo Santagata, Sandro Folkerth, Rebecca D. Kantoff, Philip Rollins, Barrett J. Lindeman, Neal I. Wen, Patrick Y. Ligon, Azra H. Beroukhim, Rameen Alexander, Brian M. Ligon, Keith L. TI Clinical implementation of integrated whole-genome copy number and mutation profiling for glioblastoma SO NEURO-ONCOLOGY LA English DT Article DE array CGH; clinical trials; genomics; genotyping; glioblastoma ID GROWTH-FACTOR RECEPTOR; HUMAN CANCERS; STEM-CELL; HYBRIDIZATION; GLIOMAS; LANDSCAPE; SAMPLES; ATRX AB Background. Multidimensional genotyping of formalin-fixed paraffin-embedded (FFPE) samples has the potential to improve diagnostics and clinical trials for brain tumors, but prospective use in the clinical setting is not yet routine. We report our experience with implementing a multiplexed copy number and mutation-testing program in a diagnostic laboratory certified by the Clinical Laboratory Improvement Amendments. Methods. We collected and analyzed clinical testing results from whole-genome array comparative genomic hybridization (OncoCopy) of 420 brain tumors, including 148 glioblastomas. Mass spectrometry-based mutation genotyping (OncoMap, 471 mutations) was performed on 86 glioblastomas. Results. OncoCopy was successful in 99% of samples for which sufficient DNA was obtained (n = 415). All clinically relevant loci for glioblastomas were detected, including amplifications (EGFR, PDGFRA, MET) and deletions (EGFRvIII, PTEN, 1p/19q). Glioblastoma patients = 40 years old had distinct profiles compared with patients >40 years. OncoMap testing reliably identified mutations in IDH1, TP53, and PTEN. Seventy-seven glioblastoma patients enrolled on trials, of whom 51% participated in targeted therapeutic trials where multiplex data informed eligibility or outcomes. Data integration identified patients with complete tumor suppressor inactivation, albeit rarely (5% of patients) due to lack of whole-gene coverage in OncoMap. Conclusions. Combined use of multiplexed copy number and mutation detection from FFPE samples in the clinical setting can efficiently replace singleton tests for clinical diagnosis and prognosis in most settings. Our results support incorporation of these assays into clinical trials as integral biomarkers and their potential to impact interpretation of results. Limited tumor suppressor variant capture by targeted genotyping highlights the need for whole-gene sequencing in glioblastoma. C1 [Ramkissoon, Shakti H.; Ramkissoon, Lori A.; Haidar, Sam; Knoff, David; Kang, Yun Jee; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Schumacher, Steven E.; Brown, Loreal; Burns, Margot; Reardon, David A.; Lee, Eudocia Q.; Rinne, Mikael L.; Norden, Andrew D.; Nayak, Lakshmi; Ruland, Sandra; Doherty, Lisa M.; LaFrankie, Debra C.; Kantoff, Philip; Rollins, Barrett J.; Wen, Patrick Y.; Beroukhim, Rameen; Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bi, Wenya Linda; Claus, Elizabeth B.; Al-Mefty, Ossama; Johnson, Mark D.; Golby, Alexandra J.; Dunn, Ian F.; Chiocca, E. Antonio] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Trippa, Lorenzo] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Horvath, Margaret; Aizer, Ayal A.; Arvold, Nils D.; Alexander, Brian M.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Russo, Andrea] Harvard Univ, Radiat Oncol Program, Boston, MA 02115 USA. [Schultz, Nikolaus] Mem Sloan Kettering Canc Ctr, Kravis Ctr Mol Oncol, New York, NY 10021 USA. [Schultz, Nikolaus] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Beroukhim, Rameen] Broad Inst, Cambridge, MA USA. [Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Ramkissoon, Shakti H.; Dubuc, Adrian; Cryan, Jane B.; Abedalthagafi, Malak; Santagata, Sandro; Folkerth, Rebecca D.; Rollins, Barrett J.; Ligon, Azra H.; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Ligon, KL (reprint author), Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.; Beroukhim, R; Ligon, KL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Alexander, BM (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.; Ligon, AH (reprint author), Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. EM aligon@partners.org; rameen_beroukhim@dfci.harvard.edu; brian_alexander@dfci.harvard.edu; keith_ligon@dfci.harvard.edu OI Knoff, David/0000-0001-6233-2893 FU Ivy Early Phase Clinical Trials Consortium; Sontag Foundation; King Abdulaziz City for Science and Technology (KACST), Saudi Arabia; [R01CA170592]; [K08NS087118-01]; [P50CA165962] FX This work was supported by grants R01CA170592 (K.L.L., P.Y.W.), K08NS087118-01 (S.H.R.), and P50CA165962 (K.L.L., P.Y.W., A.H.L.); the Ivy Early Phase Clinical Trials Consortium (K.L.L., P.Y.W., M.B., L.B.); the Sontag Foundation (K.L.L., R.B.); and the King Abdulaziz City for Science and Technology (KACST), Saudi Arabia (M.A.A.) NR 38 TC 13 Z9 13 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2015 VL 17 IS 10 BP 1344 EP 1355 DI 10.1093/neuonc/nov015 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CW1WR UT WOS:000364783100006 PM 25754088 ER PT J AU Gerstner, ER Ye, XB Duda, DG Levine, MA Mikkelsen, T Kaley, TJ Olson, JJ Nabors, BL Ahluwalia, MS Wen, PY Jain, RK Batchelor, TT Grossman, S AF Gerstner, Elizabeth R. Ye, Xiaobu Duda, Dan G. Levine, Michael A. Mikkelsen, Tom Kaley, Thomas J. Olson, Jeffrey J. Nabors, Burt L. Ahluwalia, Manmeet S. Wen, Patrick Y. Jain, Rakesh K. Batchelor, Tracy T. Grossman, Stuart TI A phase I study of cediranib in combination with cilengitide in patients with recurrent glioblastoma SO NEURO-ONCOLOGY LA English DT Article DE angiogenesis; biomarker; glioblastoma; invasion; treatment ID ANTIANGIOGENIC THERAPY; RESPONSE ASSESSMENT; TUMOR VASCULATURE; ANGIOGENESIS; BEVACIZUMAB; PROGRESSION; SURVIVAL; GLIOMAS; TRIAL; CHEMORADIATION AB Background. Despite being a highly vascularized tumor, glioblastoma response to anti-vascular endothelial growth factor (VEGF) therapy is transient, possibly because of tumor co-option of preexisting blood vessels and infiltration into surrounding brain. Integrins, which are upregulated after VEGF inhibition, may play a critical role in this resistance mechanism. We designed a study of cediranib, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, combined with cilengitide, an integrin inhibitor. Methods. This phase I study was conducted through the Adult Brain Tumor Consortium in patients with recurrent glioblastoma. Once the maximum tolerated dose was determined, 40 patients enrolled in a dose expansion cohort with 20 being exposed to anti-VEGF therapy and 20 being naive. The primary endpoint was safety. Secondary endpoints included overall survival, proportion of participants alive and progression free at 6 months, radiographic response, and exploratory analyses of physiological imaging and blood biomarkers. Results. Forty-five patients enrolled, and no dose toxicities were observed at a dose of cediranib 30 mg daily and cilengitide 2000 mg twice weekly. Complete response was seen in 2 participants, partial response in 2, stable disease in 13, and progression in 21; 7 participants were not evaluable. Median overall survival was 6.5 months, median progression-free survival was 1.9 months, and progression-free survival at 6 months was 4.4%. Plasma-soluble VEGFR2 decreased with treatment and placental growth factor, carbonic anhydrase IX, and SDF1a, and cerebral blood flow increased. Conclusions. The combination of cediranib with cilengitide was well tolerated and associated with changes in pharmacodynamic blood and imaging biomarkers. However, the survival and response rates do not warrant further development of this combination. C1 [Gerstner, Elizabeth R.; Duda, Dan G.; Jain, Rakesh K.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Ye, Xiaobu; Grossman, Stuart] Johns Hopkins Med Ctr, Baltimore, MD USA. [Gerstner, Elizabeth R.; Levine, Michael A.] Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Kaley, Thomas J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Olson, Jeffrey J.] Emory Univ, Atlanta, GA 30322 USA. [Nabors, Burt L.] Univ Alabama Birmingham, Birmingham, AL USA. [Ahluwalia, Manmeet S.] Case Comprehens Canc Ctr, Cleveland, OH USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, 55 Fruit St Yawkey 9E, Boston, MA 02114 USA. EM egerstner@mgh.harvard.edu OI Kaley, Thomas/0000-0002-2540-8518 FU Adult Brain Tumor Consortium and an American Recovery and Reinvestment Act (ARRA) grant FX This trial was funded by the Adult Brain Tumor Consortium and an American Recovery and Reinvestment Act of 2009 (ARRA) grant. NR 25 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2015 VL 17 IS 10 BP 1386 EP 1392 DI 10.1093/neuonc/nov085 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CW1WR UT WOS:000364783100010 PM 26008604 ER PT J AU Garcia, C Monroe, M Floyd, J Klepeis, V Su, H Gilbertson, J AF Garcia, Christopher Monroe, Megan Floyd, James Klepeis, Veronica Su, Hui Gilbertson, John TI Addressing Data Quality: A Necessary Step in Unlocking Anatomic Pathology Data for Complex Analytics and Computational Pathology SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract C1 [Garcia, Christopher; Floyd, James; Klepeis, Veronica; Gilbertson, John] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Monroe, Megan; Su, Hui] IBM Watson Res Ctr, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2015 VL 144 SU 2 MA 173 BP A173 EP A173 PG 1 WC Pathology SC Pathology GA CV9DJ UT WOS:000364587200174 ER PT J AU Klepeis, V Garcia, C Gilbertson, J AF Klepeis, Veronica Garcia, Chris Gilbertson, John TI Importance of Data Quality Improvement and Assessment in Anatomic Pathology SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract C1 [Klepeis, Veronica; Garcia, Chris; Gilbertson, John] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2015 VL 144 SU 2 MA 355 BP A355 EP A355 PG 1 WC Pathology SC Pathology GA CV9DJ UT WOS:000364587200356 ER PT J AU Rehman, A Zuo, CL Sheehan, C Lin, JM Yang, M Lee, H AF Rehman, Aseeb Zuo, Chunlai Sheehan, Christine Lin, Jingmei Yang, Michelle Lee, Hwajeong TI Prognostic Implication of Poorly Differentiated Clusters, Tumor Budding, and Tumor Regression in Resected Rectal Cancer Status Post Neoadjuvant Therapy SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract C1 [Rehman, Aseeb; Zuo, Chunlai; Sheehan, Christine; Lee, Hwajeong] Albany Med Ctr, Albany, NY USA. [Lin, Jingmei] Indiana Univ, Bloomington, IN 47405 USA. [Yang, Michelle] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2015 VL 144 SU 2 MA 404 BP A404 EP A404 PG 1 WC Pathology SC Pathology GA CV9DJ UT WOS:000364587200405 ER PT J AU Farr, OM Gavrieli, A Mantzoros, CS AF Farr, Olivia M. Gavrieli, Anna Mantzoros, Christos S. TI Leptin applications in 2015: what have we learned about leptin and obesity? SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE hypoleptinemia; leptin; leptin resistance; lipodystrophy; obesity ID REVERSES INSULIN-RESISTANCE; EARLY-ONSET OBESITY; FUNCTIONAL HYPOTHALAMIC AMENORRHEA; FAMILIAL PARTIAL LIPODYSTROPHY; LONG-TERM EFFICACY; REPLACEMENT THERAPY; WEIGHT-LOSS; GENERALIZED LIPODYSTROPHY; METABOLIC ADAPTATION; ANOREXIA-NERVOSA AB Purpose of reviewTo summarize previous and current advancements for leptin therapeutics, we described how leptin may be useful in leptin deficient states such as lipodystrophy, for which leptin was recently approved, and how it may be useful in the future for typical obesity.Recent findingsThe discovery of leptin in 1994 built the foundation for understanding the pathophysiology and treatment of obesity. Leptin therapy reverses morbid obesity related to congenital leptin deficiency and appears to possibly treat lipodystrophy, a finding which has led to the approval of leptin for the treatment of lipodystrophy in the USA and Japan. Typical obesity, on the other hand, is characterized by hyperleptinemia and leptin tolerance. Thus, leptin administration has proven ineffective for inducing weight loss on its own but could possibly be useful in combination with other therapies or for weight loss maintenance.SummaryLeptin is not able to treat typical obesity; however, it is effective for reversing leptin deficiency-induced obesity and is possibly useful in lipodystrophy. New mechanisms and pathways involved in leptin resistance are continuously discovered, whereas the development of new techniques and drug combinations which may improve leptin's efficacy and safety regenerate the hope for its use as an effective treatment for typical obesity. C1 Harvard Univ, Sch Med, Div Endocrinol, Boston VA Healthcare Syst, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Endocrinol Sect, Sch Med, Boston, MA 02215 USA. RP Gavrieli, A (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, 330 Brookline Ave,Stoneman 820, Boston, MA 02215 USA. EM agavriel@bidmc.harvard.edu OI Farr, Olivia/0000-0002-5182-3432 FU NICHD [5T32HD052961]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1]; NIH [5T32HD052961]; VA CSRD [1I01CX000422-01A1] FX O.M.F. is supported by a training grant through the NICHD 5T32HD052961. This was also supported by Award 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development.; NIH 5T32HD052961; VA CSRD 1I01CX000422-01A1. NR 104 TC 8 Z9 8 U1 4 U2 24 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 OCT PY 2015 VL 22 IS 5 BP 353 EP 359 DI 10.1097/MED.0000000000000184 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CV6PR UT WOS:000364392900005 PM 26313897 ER PT J AU Butsch, WS AF Butsch, W. Scott TI Obesity medications: what does the future look like? SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE beloranib; liraglutide; lorcaserin; naltrexone-bupropion; obesity medications; phentermine-topiramate ID CONTROLLED-RELEASE PHENTERMINE/TOPIRAMATE; RANDOMIZED CONTROLLED-TRIAL; SUSTAINED WEIGHT-LOSS; OVERWEIGHT ADULTS; PHASE-3 TRIAL; MANAGEMENT; METAANALYSIS; LIRAGLUTIDE; COMBINATION; LORCASERIN AB Purpose of reviewLifestyle modification remains the mainstay of treatment for obesity despite the lack of substantial long-term efficacy. For many who do not respond to lifestyle therapy and are not candidates for weight loss surgery, pharmacotherapy is a viable treatment option. Advances in understanding mechanisms of appetite control, nutrient sensing, and energy expenditure have not only helped shape current drug development but have also changed the way in which antiobesity medications are prescribed. Current antiobesity medications and pharmacological strategies will be reviewed.Recent findingsTwo new antiobesity drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved by the US Food and Drug Administration in 2014 and join four other approved obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin (Belviq), to form the largest number of medications available for the treatment of obesity. In addition, investigational drugs, like belnoranib, show promise in early clinical trials, brightening the outlook on drug development.SummaryTo combat the complex physiological system of energy regulation and the known variation of treatment response, combinatory therapies for obesity, including pharmacotherapy, are needed. Now six US Food and Drug Administration-approved antiobesity medications, including two combination medications, will allow providers to tailor obesity treatment in combination with lifestyle modification for a great number of individuals with obesity. C1 [Butsch, W. Scott] Harvard Univ, Sch Med, Div Nutr, Boston, MA USA. [Butsch, W. Scott] Massachusetts Gen Hosp, Weight Ctr, Obes Metab & Nutr Inst, Boston, MA 02114 USA. RP Butsch, WS (reprint author), MGH Weight Ctr, 50 Staniford St,Fourth Floor, Boston, MA 02114 USA. EM wbutsch@mgh.harvard.edu NR 30 TC 5 Z9 5 U1 6 U2 23 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 OCT PY 2015 VL 22 IS 5 BP 360 EP 366 DI 10.1097/MED.0000000000000192 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CV6PR UT WOS:000364392900006 PM 26313898 ER PT J AU Baumert, TF Verrier, ER Nassal, M Chung, RT Zeisel, MB AF Baumert, Thomas F. Verrier, Eloi R. Nassal, Michael Chung, Raymond T. Zeisel, Mirjam B. TI Host-targeting agents for treatment of hepatitis B virus infection SO CURRENT OPINION IN VIROLOGY LA English DT Article ID PRIMARY TUPAIA HEPATOCYTES; VIRAL-HEPATITIS; IN-VITRO; T-CELLS; ENTRY; REPLICATION; POLYPEPTIDE; INHIBITOR; APOPTOSIS; RECEPTOR AB Hepatitis B virus (HBV) infection is a major cause of chronic liver disease, including liver cirrhosis, liver failure and hepatocellular carcinoma (Ficq the second leading and fastest rising cause of cancer death world-wide. While de novo infection can be efficiently prevented by vaccination and chronic infection can be controlled using antivirals targeting the viral polymerase, the development of efficient antiviral strategies to eliminate the virus and thus to cure infection remains a key unmet medical need. The recent progress in the development of robust infectious HBV cell culture models now enables the investigation of the full viral life cycle, including a more detailed study of the molecular mechanisms of virus-host interactions responsible for viral persistence. The understanding of these virus-host interactions will be instrumental for the development of curative treatments. Host-dependency factors have recently emerged as promising candidates to treat and prevent infection by various pathogens. This review focuses on the potential of host-targeting agents (HTAs) as novel antivirals to treat and cure HBV infection. These include HTAs that inhibit de novo and re-infection, synthesis and spread of cccDNA as well as development of immune-based approaches eliminating or curing infected hepatocytes, including the eradication of viral cccDNA. C1 [Baumert, Thomas F.; Verrier, Eloi R.; Zeisel, Mirjam B.] INSERM, U1110, Inst Rech Malad Virales & Hepat, F-67000 Strasbourg, France. [Baumert, Thomas F.; Verrier, Eloi R.; Zeisel, Mirjam B.] Univ Strasbourg, F-67000 Strasbourg, France. [Baumert, Thomas F.] Inst Hosp Univ, Pole Hopatodigestif, Nouvel Hop Civil, F-67000 Strasbourg, France. [Baumert, Thomas F.; Chung, Raymond T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Liver Ctr & Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. [Nassal, Michael] Univ Hosp Freiburg, Dept Internal Med Mol Biol 2, D-79106 Freiburg, Germany. RP Baumert, TF (reprint author), INSERM, U1110, Inst Rech Malad Virales & Hepat, F-67000 Strasbourg, France. EM thomas.baumert@unistra.fr RI Zeisel, Mirjam/E-9205-2016 OI Zeisel, Mirjam/0000-0003-1606-0131 FU Inserm; University of Strasbourg; European Union [ERC-2008-AdG-233130-HEPCENT, 305600]; ANRS; French Cancer Agency (ARC) [IHU201301187]; Deutsche Forschungsgemeinschaft [NA 154/12-1, NA 154/12-2, 1202]; French National Research Agency FX The authors acknowledge support by Inserm, University of Strasbourg, the European Union (Interreg-IV-Rhin Superieur-FEDER-Hepato-Regio-Net; ERC-2008-AdG-233130-HEPCENT; FP7 305600 HepaMab; EU Infect-Era hepBccc), ANRS, the French Cancer Agency (ARC IHU201301187) and the Deutsche Forschungsgemeinschaft (NA 154/12-1,2 within the Collaborative Research Unit 1202). This work has been published under the framework of the LABEX ANR-10-LAB-28 and benefits from a funding from the state managed by the French National Research Agency as part of the Investments for the future program. NR 62 TC 8 Z9 8 U1 4 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1879-6257 J9 CURR OPIN VIROL JI Curr. Opin. Virol. PD OCT PY 2015 VL 14 BP 41 EP 46 DI 10.1016/j.coviro.2015.07.009 PG 6 WC Virology SC Virology GA CW2BW UT WOS:000364797100008 PM 26262886 ER PT J AU Das, A Brugge, W Mishra, G Smith, DM Sachdev, M Ellsworth, E AF Das, Ananya Brugge, William Mishra, Girish Smith, Dennis M. Sachdev, Mankanwal Ellsworth, Eric TI Managing incidental pancreatic cystic neoplasms with integrated molecular pathology is a cost-effective strategy SO Endoscopy International Open LA English DT Article ID BARRETTS-ESOPHAGUS; MANAGEMENT; DIAGNOSIS; GUIDELINES; HEALTH; FLUID; RISK; CM AB Background and study aims: Current guidelines recommend using endoscopic ultrasound (EUS), carcinoembryonic antigen (CEA) testing and cytology to manage incidental pancreatic cystic neoplasms (PCN); however, studies suggest a strategy including integrated molecular pathology (IMP) of cyst fluid may further aid in predicting risk of malignancy. Here, we evaluate several strategies for diagnosing and managing asymptomatic PCN using healthcare economic modeling. Patients and methods: A third-party-payer perspective Markov decision model examined four management strategies in a hypothetical cohort of 1000 asymptomatic patients incidentally found to have a 3cm solitary pancreatic cystic lesion. Strategy I used cross-sectional imaging, recommended surgery only if symptoms or risk factors emerged. Strategy II considered patients for resection without initial EUS.Strategy III (EUS+CEA+Cytology) referred only those with mucinous cysts (CEA >192ng/mL) for resection. Strategy IV implemented IMP; a commercially available panel provided a Benign, Mucinous, or Aggressive classification based on the level of mutational change in cyst fluid. Benign and Mucinous patients were followed with surveillance; Aggressive patients were referred for resection. Quality-adjusted life-years (QALY), relative risk with 95%CI, Number Needed to Treat (NNT), and incremental cost-effectiveness ratios were calculated. Results: Strategy IV provided the greatest increase in QALY at nearly identical cost to the cheapest approach, Strategy I. Relative risk of malignancy compared to the current standard of care and nearest competing strategy, Strategy III, was 0.18 (95%CI 0.06-0.53) with an NNT of 56 (95%CI 34-120). Conclusions: Use of IMP was the most cost-effective strategy, supporting its routine clinical use. C1 [Das, Ananya; Sachdev, Mankanwal] Arizona Ctr Digest Hlth, Gilbert, AZ 85295 USA. [Brugge, William] Massachusetts Gen Hosp, Digest Healthcare Ctr, Boston, MA 02114 USA. [Mishra, Girish] Wake Forest Baptist Hlth, Dept Gastroenterol, Winston Salem, NC USA. [Smith, Dennis M.; Ellsworth, Eric] RedPath Integrated Pathol, Pittsburgh, PA USA. RP Das, A (reprint author), Arizona Ctr Digest Hlth, 2680 S Valvista Dr,Suite 116, Gilbert, AZ 85295 USA. EM adas@azcdh.com NR 31 TC 1 Z9 1 U1 2 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 2364-3722 EI 2196-9736 J9 ENDOSC INT OPEN JI Endosc. Int. Open PD OCT PY 2015 VL 3 IS 5 BP E479 EP E486 DI 10.1055/s-0034-1392016 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CV5TO UT WOS:000364334300018 PM 26528505 ER PT J AU Nishihara, R VanderWeele, TJ Shibuya, K Mittleman, MA Wang, ML Field, AE Giovannucci, E Lochhead, P Ogino, S AF Nishihara, Reiko VanderWeele, Tyler J. Shibuya, Kenji Mittleman, Murray A. Wang, Molin Field, Alison E. Giovannucci, Edward Lochhead, Paul Ogino, Shuji TI Molecular pathological epidemiology gives clues to paradoxical findings SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Bias; Cardiovascular disease; Molecular diagnostics; Multifactorial diseases; Personalized medicine ID BODY-MASS INDEX; ISLAND METHYLATOR PHENOTYPE; COLORECTAL-CANCER RISK; RENAL-CELL CARCINOMA; LIFE-STYLE FACTORS; MICROSATELLITE-INSTABILITY; OBESITY PARADOX; CARDIOVASCULAR-DISEASE; PROMOTER METHYLATION; PRECISION-MEDICINE AB A number of epidemiologic studies have described what appear to be paradoxical associations, where an incongruous relationship is observed between a certain well-established risk factor for disease incidence and favorable clinical outcome among patients with that disease. For example, the "obesity paradox" represents the association between obesity and better survival among patients with a certain disease such as coronary heart disease. Paradoxical observations cause vexing clinical and public health problems as they raise questions on causal relationships and hinder the development of effective interventions. Compelling evidence indicates that pathogenic processes encompass molecular alterations within cells and the microenvironment, influenced by various exogenous and endogenous exposures, and that interpersonal heterogeneity in molecular pathology and pathophysiology exists among patients with any given disease. In this article, we introduce methods of the emerging integrative interdisciplinary field of molecular pathological epidemiology (MPE), which is founded on the unique disease principle and disease continuum theory. We analyze and decipher apparent paradoxical findings, utilizing the MPE approach and available literature data on tumor somatic genetic and epigenetic characteristics. Through our analyses in colorectal cancer, renal cell carcinoma, and glioblastoma (malignant brain tumor), we can readily explain paradoxical associations between disease risk factors and better prognosis among disease patients. The MPE paradigm and approach can be applied to not only neoplasms but also various non-neoplastic diseases where there exists indisputable ubiquitous heterogeneity of pathogenesis and molecular pathology. The MPE paradigm including consideration of disease heterogeneity plays an essential role in advancements of precision medicine and public health. C1 [Nishihara, Reiko; Giovannucci, Edward] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Nishihara, Reiko; Ogino, Shuji] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Nishihara, Reiko; Shibuya, Kenji] Univ Tokyo, Dept Global Hlth Policy, Grad Sch Med, Bunkyo Ku, Tokyo, Japan. [VanderWeele, Tyler J.; Mittleman, Murray A.; Wang, Molin; Field, Alison E.; Giovannucci, Edward; Ogino, Shuji] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [VanderWeele, Tyler J.; Wang, Molin] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Mittleman, Murray A.] Harvard Univ, Sch Med, Cardiovasc Epidemiol Res Unit, Dept Med,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Wang, Molin; Field, Alison E.; Giovannucci, Edward] Harvard Univ, Sch Med, Channing Div Network Med, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Field, Alison E.] Boston Childrens Hosp, Div Adolescent Med, Boston, MA 02115 USA. [Field, Alison E.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Lochhead, Paul] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Nishihara, R (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM rnishiha@hsph.harvard.edu; shuji_ogino@dfci.harvard.edu FU U.S. National Institutes of Health (NIH) [R01 CA151993, R35 CA197735, K07 CA190673] FX This work was supported by U.S. National Institutes of Health (NIH) Grants [R01 CA151993 to S.O.; R35 CA197735 to S.O., and K07 CA190673 to R.N.]. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 85 TC 9 Z9 9 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD OCT PY 2015 VL 30 IS 10 BP 1129 EP 1135 DI 10.1007/s10654-015-0088-4 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CV8FP UT WOS:000364516600009 PM 26445996 ER PT J AU Chang, HB Gao, X Nepomuceno, R Hu, SS Sun, DD AF Chang, He Benny Gao, Xin Nepomuceno, Rachel Hu, Shaoshan Sun, Dandan TI Na+/H+ exchanger in the regulation of platelet activation and paradoxical effects of cariporide SO EXPERIMENTAL NEUROLOGY LA English DT Article; Proceedings Paper CT 3rd Pangu Stroke Conference CY OCT 10-12, 2014 CL Beijing, PEOPLES R CHINA DE Cariporide; EXPEDITION trial; HOE 642; Ischemia reperfusion; NHE1; Platelet aggregation ID SODIUM-HYDROGEN EXCHANGE; LOW-DENSITY-LIPOPROTEIN; NHE-1 INHIBITOR CARIPORIDE; TRANSIENT ISCHEMIC ATTACK; PORCINE BLOOD-PLATELETS; MYOCARDIAL-INFARCTION; CLINICAL-IMPLICATIONS; CEREBRAL-ISCHEMIA; PROTEIN-KINASE; MINOR STROKE AB Platelets are anucleated cell fragments derived from mature megalcaryocytes and function in hemostasis when the endothelium is injured. Hemostasis involving platelets can be divided into four phases: adhesion, activation, secretion, and aggregation. Platelet activation requires a rise in intracellular Ca2+ concentrations and results in both a morphological change and the secretion of platelet granule contents. Na+/H+ exchanger isoform I (NHE1) regulates the intracellular pH (pH(i)) and the volume of platelets. In addition, NHE1 plays a large role in platelet activation. Thrombus generation involves NHE1 activation and an increase in [Ca2+](i), which results from NHE1-mediated Na+ overload and the reversal of the Na+/Ca2+ exchanger. Cariporide (HOE-642), a potent NHE1 inhibitor, has inhibitory effects on the degranulation of human platelets, the formation of plateletleukocyte-aggregates, and the activation of the GPIIb/IIIa receptor (PAC-1). However, despite the demonstrated protection against myocardial infarction as mediated by cariporide in patients undergoing coronary artery bypass graft surgery, the EXPEDITION clinical trial revealed that cariporide treatment increased mortality due to thromboembolic stroke. These findings suggest that a better understanding of NHE1 and its effect on platelet function and procoagulant factor regulation is warranted in order to develop therapies using NHE inhibitors. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chang, He Benny; Gao, Xin; Nepomuceno, Rachel; Sun, Dandan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Gao, Xin; Hu, Shaoshan] Harbin Med Univ, Affiliated Hosp 2, Dept Neurol Surg, Harbin 150086, Peoples R China. [Sun, Dandan] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA. RP Sun, DD (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-598 South Biomed Sci Tower BST, Pittsburgh, PA 15213 USA. EM sund@upmc.edu OI Nepomuceno, Rachel/0000-0003-2358-7820 FU NIH [R01 NS048216]; Chinese Academy of Sciences Program [2014 YS14C11]; Technology Cooperation of Province FX This work was supported in part by NIH grant R01 NS048216 (DS) and Technology Cooperation of Province and Chinese Academy of Sciences Program 2014 YS14C11 (SH). NR 66 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2015 VL 272 SI SI BP 11 EP 16 DI 10.1016/j.expneurol.2014.12.023 PG 6 WC Neurosciences SC Neurosciences & Neurology GA CV6AS UT WOS:000364353700003 PM 25595121 ER PT J AU Shi, H Hu, XM Leak, RK Shi, YJ An, CR Suenaga, J Chen, J Gao, YQ AF Shi, Hong Hu, Xiaoming Leak, Rehana K. Shi, Yejie An, Chengrui Suenaga, Jun Chen, Jun Gao, Yanqin TI Demyelination as a rational therapeutic target for ischemic or traumatic brain injury SO EXPERIMENTAL NEUROLOGY LA English DT Article; Proceedings Paper CT 3rd Pangu Stroke Conference CY OCT 10-12, 2014 CL Beijing, PEOPLES R CHINA DE Demyelination; Oligodendrocyte; Remyelination; Cerebral ischemia; Traumatic brain injury ID OLIGODENDROCYTE PROGENITOR CELLS; CENTRAL-NERVOUS-SYSTEM; WHITE-MATTER INJURY; FOCAL CEREBRAL-ISCHEMIA; NECROSIS-FACTOR-ALPHA; MICROGLIA/MACROPHAGE POLARIZATION DYNAMICS; RECEPTOR/IL-6 FUSION PROTEIN; SPINAL-CORD-INJURY; MITOCHONDRIAL DYSFUNCTION; MULTIPLE-SCLEROSIS AB Previous research on stroke and traumatic brain injury (TBI) heavily emphasized pathological alterations in neuronal cells within gray matter. However, recent studies have highlighted the equal importance of white matter integrity in long-term recovery from these conditions. Demyelination is a major component of white matter injury and is characterized by loss of the myelin sheath and oligodendrocyte cell death. Demyelination contributes significantly to long-term sensorimotor and cognitive deficits because the adult brain only has limited capacity for oligodendrocyte regeneration and axonal remyelination. In the current review, we will provide an overview of the major causes of demyelination and oligodendrocyte cell death following acute brain injuries, and discuss the crosstalk between myelin, axons, microglia, and astrocytes during the process of demyelination. Recent discoveries of molecules that regulate the processes of remyelination may provide novel therapeutic targets to restore white matter integrity and improve long-term neurological recovery in stroke or TBI patients. (C) 2015 Elsevier Inc. All rights reserved. C1 [Shi, Hong; Hu, Xiaoming; Shi, Yejie; An, Chengrui; Chen, Jun; Gao, Yanqin] Fudan Univ, State Key Lab Med Neurobiol, Inst Brain Sci, Shanghai 200032, Peoples R China. [Shi, Hong; Hu, Xiaoming; Shi, Yejie; An, Chengrui; Chen, Jun; Gao, Yanqin] Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200032, Peoples R China. [Shi, Hong] Tongji Univ, Shanghai Pulm Hosp, Dept Anesthesiol, Shanghai 200433, Peoples R China. [Hu, Xiaoming; Shi, Yejie; Suenaga, Jun; Chen, Jun; Gao, Yanqin] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Sch Med, Pittsburgh, PA 15213 USA. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Hu, Xiaoming; Shi, Yejie; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. RP Chen, J (reprint author), Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Sch Med, 3500 Terrace St, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu; yqgao@shmu.edu.cn RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417; Shi, Yejie/0000-0001-7502-9201 FU Natural Science Foundation of Shanghai [14ZR1434600]; Natural Science Foundation of China [81171149, 81371306, 81228008]; Shanghai Committee of Science and Technology Research Program [14431907002]; American Heart Association Scientist Development [13SDG14570025]; Doctoral Training Fund from the Chinese Ministry of Education [20120071110042]; NIH/NINDS [NS36736, NS43802, NS45048, NS089534]; Department of Veterans Affairs Research Career Scientist Award and RR D Merit Review [1l01IX000420] FX This work was supported by the Natural Science Foundation of Shanghai grant 14ZR1434600 (to H.S.), the Natural Science Foundation of China grants 81171149 and 81371306 (to Y.G.), and 81228008 (to J.C.), the Shanghai Committee of Science and Technology Research Program 14431907002 (to Y.G.), the American Heart Association Scientist Development grant 13SDG14570025 (to X.H.), Doctoral Training Fund from the Chinese Ministry of Education 20120071110042 (to J.C.), NIH/NINDS grants NS36736, NS43802, NS45048 and NS089534 (to J.C.), and the Department of Veterans Affairs Research Career Scientist Award and RR & D Merit Review 1l01IX000420 (to J.C.). NR 177 TC 4 Z9 4 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2015 VL 272 SI SI BP 17 EP 25 DI 10.1016/j.expneurol.2015.03.017 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CV6AS UT WOS:000364353700004 PM 25819104 ER PT J AU Suenaga, J Hu, XM Pu, HJ Shi, YJ Hassan, SH Xu, MY Leak, RK Stetler, RA Gao, YQ Chen, J AF Suenaga, Jun Hu, Xiaoming Pu, Hongjian Shi, Yejie Hassan, Sulaiman Habib Xu, Mingyue Leak, Rehana K. Stetler, R. Anne Gao, Yanqin Chen, Jun TI White matter injury and microglia/macrophage polarization are strongly linked with age-related long-term deficits in neurological function after stroke SO EXPERIMENTAL NEUROLOGY LA English DT Article; Proceedings Paper CT 3rd Pangu Stroke Conference CY OCT 10-12, 2014 CL Beijing, PEOPLES R CHINA DE Aging; Microglia; Distal middle cerebral artery occlusion (dMCAO); Cerebral blood perfusion ID MIDDLE CEREBRAL-ARTERY; ISCHEMIC BRAIN-INJURY; PERIPHERAL IMMUNE-SYSTEM; INFLAMMATORY MEDIATORS; OCCLUSION; MICE; RATS; HYPOPERFUSION; ACTIVATION; CONTRIBUTE AB Most of the successes in experimental models of stroke have not translated well to the clinic. One potential reason for this failure is that stroke mainly afflicts the elderly and the majority of experimental stroke studies rely on data gathered from young adult animals. Therefore, in the present study we established a reliable, reproducible model of stroke with low mortality in aged (18 month) male mice and contrasted their pathophysiological Changes with those in young (2 month) animals. To this end, mice were subjected to permanent tandem occlusion of the left distal middle cerebral artery (dMCAO) with ipsilateral common carotid artery occlusion (CCAO). Cerebral blood flow (CBF) was evaluated repeatedly during and after stroke. Reduction of CBF was more dramatic and sustained in aged mice. Aged mice exhibited more severe long-term sensorimotor deficits, as manifested by deterioration of performance in the Rotarod and hanging wire tests up to and after stroke. Aged mice also exhibited significantly worse long-term cognitive deficits after stroke, as measured by the Morris water maze test Consistent with these behavioral observations, brain infarct size and neuronal tissue loss after dMCAO were significantly larger in aged mice at 2 d and 14 d, respectively. The young versus aged difference in neuronal tissue loss, however, did not persist until 35 d after dMCAO. In contrast to the transient difference in neuronal tissue loss, we found significant and long lasting deterioration of white matter in aged animals, as revealed by the loss of myelin basic protein (MBP) staining in the striatum at 35 d after dMCAO. We further examined the expression of M1 (CD16/CD32) and M2 (CD206) markers in Iba-1(+) microglia by double immunofluorescent staining. In both young and aged mice, the expression of M2 markers peaked around 7 d after stroke whereas the expression of M1 markers peaked around 14 d after stroke, suggesting a progressive M2-to-M1 phenotype shift in both groups. However, aged mice exhibited significantly reduced M2 polarization compared to young adults. Remarkably, we discovered a strong positive correlation between favorable neurological outcomes after dMCAO and MBP levels or the number of M2 microglia/macrophages. In conclusion, our studies suggest that the distal MCAO stroke model consistently results in ischemic brain injury with long-term behavioral deficits, and is therefore suitable for the evaluation of long-term stroke outcomes. Furthermore, aged mice exhibit deterioration of functional outcomes after stroke and this deterioration is linked to white matter damage and reductions in M2 microglia/macrophage polarization. (C) 2015 Elsevier Inc. All rights reserved. C1 [Suenaga, Jun; Hu, Xiaoming; Pu, Hongjian; Shi, Yejie; Hassan, Sulaiman Habib; Stetler, R. Anne; Chen, Jun] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Sch Med, Pittsburgh, PA 15213 USA. [Hu, Xiaoming; Pu, Hongjian; Xu, Mingyue; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Hu, Xiaoming; Pu, Hongjian; Xu, Mingyue; Gao, Yanqin; Chen, Jun] Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200032, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Hu, Xiaoming; Shi, Yejie; Stetler, R. Anne; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. RP Gao, YQ (reprint author), Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. EM yqgao@shmu.edu.cn; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417; Shi, Yejie/0000-0001-7502-9201 FU U.S. National Institutes of Health [NS36736, NS43802, NS45048, NS089534]; U.S. Department of Veterans Affairs Research Career Scientist Award and RRD Merit Review [I01RX000420]; Rotary Foundation Global Scholarship [GG1412044]; American Heart Association Scientist Development [13SDG14570025]; Postdoctoral Fellowship Award [15POST22260011]; Chinese Natural Science Foundation [81020108021, 81171149, 81371306, J1210041, 81228008] FX This work was supported by U.S. National Institutes of Health grants NS36736, NS43802, NS45048 and NS089534 (to JC), U.S. Department of Veterans Affairs Research Career Scientist Award and RR&D Merit Review I01RX000420 (to JC), Rotary Foundation Global Scholarship grant GG1412044 (to JS), American Heart Association Scientist Development grant 13SDG14570025 (to XH), Postdoctoral Fellowship Award 15POST22260011 (to YS), and Chinese Natural Science Foundation grants 81020108021, 81171149, 81371306 and J1210041 (to YG), and 81228008 (to JC). NR 48 TC 18 Z9 18 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 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2015 VL 272 SI SI BP 109 EP 119 DI 10.1016/j.expneurol.2015.03.021 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CV6AS UT WOS:000364353700013 PM 25836044 ER PT J AU Zhang, WT Wang, HL Zhang, H Leak, RK Shi, YJ Hu, XM Gao, YQ Chen, J AF Zhang, Wenting Wang, Hailian Zhang, Hui Leak, Rehana K. Shi, Yejie Hu, Xiaoming Gao, Yanqin Chen, Jun TI Dietary supplementation with omega-3 polyunsaturated fatty acids robustly promotes neurovascular restorative dynamics and improves neurological functions after stroke SO EXPERIMENTAL NEUROLOGY LA English DT Article; Proceedings Paper CT 3rd Pangu Stroke Conference CY OCT 10-12, 2014 CL Beijing, PEOPLES R CHINA DE Docosahexaenoic acid; Eicosapentaenoic acid; Revascularization; Angiogenesis; Neurogenesis; Oligodendrogenesis; Angiopoietin 1; Oligodendrocyte precursor cell ID ISCHEMIC BRAIN-INJURY; FACTOR-INDUCED ANGIOGENESIS; VASCULAR NEURAL-NETWORK; NEUROBLAST MIGRATION; ENDOGENOUS NEUROGENESIS; CEREBRAL-ISCHEMIA; ENDOTHELIAL-CELLS; FISH CONSUMPTION; STEM-CELLS; STRATEGIES AB Stroke is a devastating neurological disease with no satisfactory therapies to preserve long-term neurological function, perhaps due to the sole emphasis on neuronal survival in most preclinical studies. Recent studies have revealed the importance of protecting multiple cell types in the injured brain, such as oligodendrocytes and components of the neurovascular unit, before long-lasting recovery of function can be achieved. For example, revascularization in the ischemic penumbra is critical to provide various neurotrophic factors that enhance the survival and activity of neurons and other progenitor cells, such as oligodendrocyte precursor cells. In the present study, we hypothesized that chronic dietary supplementation with fish oil promotes post-stroke angiogenesis, neurogenesis, and oligodendrogenesis, thereby leading to long-term functional improvements. Mice received dietary supplementation with n-3 PUFA-enriched fish oil for three months before and up to one month after stroke. As expected, dietary n-3 PUFAs significantly increased levels of n-3 PUFAs in the brain and improved long-term behavioral outcomes after cerebral ischemia. n-3 PUFAs also robustly improved revascularization and angiogenesis and boosted the survival of NeuN/BrdU labeled newborn neurons up to 35 days after stroke injury. Furthermore, these pro-neurogenic effects were accompanied by robust oligodendrogenesis. Thus, this is the first study to demonstrate that chronic dietary intake of n-3 PUFAs is an effective prophylactic measure not only to protect against ischemic injury for the long term but also to actively promote neurovascular restorative dynamics and brain repair. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zhang, Wenting; Wang, Hailian; Zhang, Hui; Hu, Xiaoming; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Zhang, Wenting; Wang, Hailian; Zhang, Hui; Hu, Xiaoming; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Zhang, Wenting; Wang, Hailian; Zhang, Hui; Hu, Xiaoming; Gao, Yanqin; Chen, Jun] Fudan Univ, Huashan Hosp, Dept Anesthesiol, Shanghai 200032, Peoples R China. [Zhang, Wenting; Wang, Hailian; Zhang, Hui; Hu, Xiaoming; Gao, Yanqin; Chen, Jun] Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai 200032, Peoples R China. [Zhang, Wenting; Shi, Yejie; Hu, Xiaoming; Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Shi, Yejie; Hu, Xiaoming; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. RP Zhang, WT (reprint author), Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. EM wtzhang@fudan.edu.cn; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417 FU U.S. National Institutes of Health [NS36736, NS43802, NS45048]; U.S. Department of Veterans Affairs Research Career Scientist Award and RR D Merit Review [RX-000420-01]; Chinese Natural Science Foundation [81020108021, 81171149, 81371306, 81228008, 81301123]; Shanghai Committee of Science and Technology Support Program [14431907002]; Ministry of Education of China PhD-training [20120071110042]; China Postdoctoral Science Foundation [20110490665]; Shanghai Postdoctoral Sustentation Fund [11R21410500]; National Natural Science Foundation [81100978, 81471332] FX W.Z. and H.W. contributed equally to this research. This project was supported by the U.S. National Institutes of Health grants NS36736, NS43802 and NS45048 (to J.C.), the U.S. Department of Veterans Affairs Research Career Scientist Award and RR & D Merit Review RX-000420-01 (to J.C.), the Chinese Natural Science Foundation grants 81020108021, 81171149, 81371306 (to Y.G.), 81228008 (to J.C.), 81301123 (to H.W.), the Shanghai Committee of Science and Technology Support Program 14431907002 (to Y.G.), and the Ministry of Education of China PhD-training grant 20120071110042 (to J.C.). W.Z. was supported by the China Postdoctoral Science Foundation grants (No. 20110490665), the Shanghai Postdoctoral Sustentation Fund (No. 11R21410500), and the National Natural Science Foundation grants (No. 81100978 and No. 81471332). We thank Shiduo Lu for performing animal surgery and Hui Gao for excellent administrative support. NR 56 TC 4 Z9 4 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2015 VL 272 SI SI BP 170 EP 180 DI 10.1016/j.expneurol.2015.03.005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CV6AS UT WOS:000364353700020 PM 25771800 ER PT J AU Chousterman, BG Swirski, FK AF Chousterman, Benjamin G. Swirski, Filip K. TI Innate response activator B cells: origins and functions SO INTERNATIONAL IMMUNOLOGY LA English DT Review DE B1a cells; GM-CSF; IgM; IL-3; innate immunity; IRA B cells ID COLONY-STIMULATING FACTOR; MYOCARDIAL-INFARCTION; V(D)J RECOMBINATION; CHEMOKINE RECEPTOR; GERMINAL-CENTERS; DEFICIENT MICE; BONE-MARROW; T-CELLS; LYMPHOCYTES; ATHEROSCLEROSIS AB Innate response activator (IRA) B cells are a subset of B-1a derived B cells that produce the growth factors granulocyte macrophage colony stimulating factor and IL-3. In mouse models of sepsis and pneumonia, B-1a B cells residing in serosal sites recognize bacteria, migrate to the spleen or lung, and differentiate to IRA B cells that then contribute to the host response by amplifying inflammation and producing polyreactive IgM. In atherosclerosis, IRA B cells accumulate in the spleen, where they promote extramedullary hematopoiesis and activate classical dendritic cells. In this review, we focus on the ontogeny and function of IRA B cells in acute and chronic inflammation. C1 [Chousterman, Benjamin G.; Swirski, Filip K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Chousterman, BG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM bchouster@gmail.com FU Societe Francaise d'Anesthesie et de Reanimation (SFAR); Philippe Foundation; Howard M. Goodman Fellowship; [R01HL095612]; [R56AI104695] FX This work was supported by grants R01HL095612, R56AI104695, and Howard M. Goodman Fellowship (to F.K.S.); Societe Francaise d'Anesthesie et de Reanimation (SFAR), and Philippe Foundation (to B.G.C.). NR 59 TC 4 Z9 4 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 EI 1460-2377 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 2015 VL 27 IS 10 BP 537 EP 541 DI 10.1093/intimm/dxv028 PG 5 WC Immunology SC Immunology GA CW1QT UT WOS:000364767100010 PM 25957266 ER PT J AU Strasser-Weippl, K Chavarri-Guerra, Y Villarreal-Garza, C Bychkovsky, BL Debiasi, M Liedke, PER Soto-Perez-De-Celis, E Dizon, D Cazap, E Lopes, GD Touya, D Nunes, JS St Louis, J Vail, C Bukowski, A Ramos-Elias, P Unger-Saldana, K Brandao, DF Ferreyra, ME Luciani, S Nogueira-Rodrigues, A Calabrich, AFD Del Carmen, MG Rauh-Hain, JA Schmeler, K Sala, R Goss, PE AF Strasser-Weippl, Kathrin Chavarri-Guerra, Yanin Villarreal-Garza, Cynthia Bychkovsky, Brittany L. Debiasi, Marcio Liedke, Pedro E. R. Soto-Perez-de-Celis, Enrique Dizon, Don Cazap, Eduardo de Lima Lopes, Gilberto, Jr. Touya, Diego Nunes, Joao Soares St Louis, Jessica Vail, Caroline Bukowski, Alexandra Ramos-Elias, Pier Unger-Saldana, Karla Brandao, Denise Froes Ferreyra, Mayra E. Luciani, Silvana Nogueira-Rodrigues, Angelica de Carvalho Calabrich, Aknar Freire Del Carmen, Marcela G. Rauh-Hain, Jose Alejandro Schmeler, Kathleen Sala, Ral Goss, Paul E. TI Progress and remaining challenges for cancer control in Latin America and the Caribbean SO LANCET ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; WOOD-SMOKE EXPOSURE; PALLIATIVE CARE DEVELOPMENT; CLUSTER-RANDOMIZED TRIAL; MIDDLE-INCOME COUNTRIES; ECOLOGICAL TIME-SERIES; CERVICAL-CANCER; BREAST-CANCER; HEALTH-CARE; NONCOMMUNICABLE DISEASES AB Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention. C1 [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol & Hematol, Vienna, Austria. [Strasser-Weippl, Kathrin; Chavarri-Guerra, Yanin; St Louis, Jessica; Vail, Caroline; Bukowski, Alexandra; Goss, Paul E.] Global Canc Inst, Boston, MA USA. [Chavarri-Guerra, Yanin] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Hematooncol Dept, Mexico City, DF, Mexico. [Soto-Perez-de-Celis, Enrique] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Hematooncol Dept, Dept Geriatr, Mexico City, DF, Mexico. [Chavarri-Guerra, Yanin; St Louis, Jessica; Vail, Caroline; Bukowski, Alexandra; Goss, Paul E.] Massachusetts Gen Hosp, Avon Breast Canc Ctr Excellence, Boston, MA 02114 USA. [Del Carmen, Marcela G.] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [Dizon, Don; Rauh-Hain, Jose Alejandro] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Villarreal-Garza, Cynthia; Ramos-Elias, Pier] Tecnol Monterrey, Ctr Canc Mama, Inst Cancerol, Monterrey, Nuevo Leon, Mexico. [Unger-Saldana, Karla] Inst Nacl Cancerol, Cetedra CONACYT, Unidad Epidemiol, Mexico City, DF, Mexico. [Villarreal-Garza, Cynthia] Inst Nacl Cancerol, Dept Invest & Tumores Mamarios, Mexico City, DF, Mexico. [Bychkovsky, Brittany L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bychkovsky, Brittany L.; Dizon, Don; Del Carmen, Marcela G.; Rauh-Hain, Jose Alejandro; Goss, Paul E.] Harvard Univ, Sch Med, Boston, MA USA. [Debiasi, Marcio] Hosp Mae Deus, Porto Alegre, RS, Brazil. [Debiasi, Marcio] Hosp Sao Lucas PUCRS, Porto Alegre, RS, Brazil. [Liedke, Pedro E. R.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Liedke, Pedro E. R.] Inst Canc Mae Deus, Porto Alegre, RS, Brazil. [Cazap, Eduardo] Soc Latinoamer & Caribe Oncol Med, Buenos Aires, DF, Argentina. [de Lima Lopes, Gilberto, Jr.] Ctr Paulista Oncol & Oncoclin, Brasil Grp, Med Oncol, Sao Paulo, Brazil. [de Lima Lopes, Gilberto, Jr.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Touya, Diego] Univ Republica, Dept Oncol, Montevideo, Uruguay. [Nunes, Joao Soares] Hosp Canc Barretos, Barretos, SP, Brazil. [Brandao, Denise Froes] Univ Fed Sao Paulo Brazil, Sao Paulo, Brazil. [Ferreyra, Mayra E.] Maria Curie Hosp, Dept Oncol, Buenos Aires, DF, Argentina. [Luciani, Silvana] Pan Amer Hlth Org, Dept Noncommunicable Dis & Mental Hlth, Washington, DC USA. [Nogueira-Rodrigues, Angelica] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [de Carvalho Calabrich, Aknar Freire] Clin AMO, Brazilian Gynecol Oncol Grp, EVA Grp Brasileiro Tumores Ginecol, Salvador, BA, Brazil. [Schmeler, Kathleen] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sala, Ral] GAICO, Rosario, Santa Fe, Argentina. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Avon Breast Canc Ctr Excellence, Ctr Canc, 55 Fruit St,Lawrence House, Boston, MA 02114 USA. EM pgoss@mgh.harvard.edu FU Avon Foundation, New York, NY, USA FX PEG, JSL, AB, and DFB are supported by the Avon Foundation, New York, NY, USA. NR 239 TC 13 Z9 15 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2015 VL 16 IS 14 BP 1405 EP 1438 PG 34 WC Oncology SC Oncology GA CV3AC UT WOS:000364129400005 PM 26522157 ER PT J AU Frigerio, A Tan, OT AF Frigerio, Alice Tan, Oon T. TI Laser Applications for Benign Oral Lesions SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE Alexandrite laser; free flap; hereditary hemorragic telengectasia; infantile hemangioma; intraoral vascular malformation; port-wine stain; pyogenic granuloma; pulsed dye laser; oral cavity ID VASCULAR MALFORMATIONS; ARTERIOVENOUS-MALFORMATIONS; DYE-LASER; MANAGEMENT; YAG AB Background and Objective: Different subspecialists treat benign intraoral lesions using various approaches including surgical excision, medical therapy, sclerotherapy, and laser photocoagulation. The goal of this study was to establish whether lasers could effectively target and destroy oral lesions containing endogenous chromophores, while minimizing injury to unaffected adjacent tissues and critical structures. Materials and Methods: This retrospective study involved 26 cases of benign oral lesions, both vascular and pigmented, which were addressed by means of selective laser treatment. Pathologies were port-wine stains, hereditary hemorragic teleangectasia, hemangiomas, venous and arteriovenous malformations, pyogenic granuloma, and hairy reconstructive flaps. Electronic medical records and photographic documentation were reviewed. Three blinded staff personnel not involved with patient care in this study evaluated photographs taken prior to the first and after the final laser treatments. Observers rated the percentage clearance of the lesions or the ablation of bleeding, and the assessed values were averaged for each patient. Results: An average of 30-95% lightening was observed in the intraoral port-wine stains, 90% in the hemangiomas, 70% in arteriovenous malformations, 81% for venous malformations, 86% for venous lakes, and 100% for the pyogenic granuloma. Bleeding was ablated in all hereditary hemorrhagic telangiectasia lesions treated using the pulsed dye laser with or without the Alexandrite laser. Intraoral hair growing on the skin paddle of microvascular flaps was completely removed in one of the three cases treated using the Alexandrite laser. In the two remaining cases, some hair removal was achieved, but because the residual hairs were grey or white (absence of melanocytic chromophore), photocoagulation was less effective. Conclusion: Lasers are a safe and effective means to selectively destroy specific chromphores. Such specific targeting ensures complete destruction of pathological tissue, decreasing the possibility of relapse and/or recurrence. Selective laser treatment of benign intraoral lesions represents a niche application that fills a gap in the multidisciplinary management of several conditions such as oral vascular anomalies and hairy reconstructive flaps. Lasers Surg. Med. 47: 643-650, 2015. (C) 2015 Wiley Periodicals, Inc C1 [Frigerio, Alice; Tan, Oon T.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm,Carolyn & Peter Ly, Div Facial Plast & Reconstruct Surg,Dept Otol & L, Boston, MA 02114 USA. RP Frigerio, A (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm,Carolyn & Peter Ly, Div Facial Plast & Reconstruct Surg,Dept Otol & L, 243 Charles St, Boston, MA 02114 USA. EM alice_frigerio@meei.harvard.edu FU Lynch Foundation FX Contract grant sponsor: Lynch Foundation. NR 15 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD OCT PY 2015 VL 47 IS 8 BP 643 EP 650 DI 10.1002/lsm.22404 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA CV9VK UT WOS:000364635300006 PM 26308664 ER PT J AU Mercado, RC Wiltsey-Stirman, S Iverson, KM AF Mercado, Rowena C. Wiltsey-Stirman, Shannon Iverson, Katherine M. TI Impact of Childhood Abuse on Physical and Mental Health Status and Health Care Utilization Among Female Veterans SO MILITARY MEDICINE LA English DT Article ID MILITARY SEXUAL TRAUMA; POSTTRAUMATIC-STRESS-DISORDER; QUALITY-OF-LIFE; WOMEN VETERANS; PSYCHOMETRIC PROPERTIES; RETROSPECTIVE REPORTS; COMBAT EXPOSURE; PTSD CHECKLIST; MALTREATMENT; EXPERIENCES AB Objective: To determine whether childhood abuse predicts health symptoms and health care use among female veterans. Methods: Participants were 369 female patients at Veterans Affairs hospitals in New England who completed a mail survey. Multiple regression analyses were conducted to determine the differential impact of childhood physical abuse and childhood sexual abuse on health symptoms and health care use, while accounting for age, race, military branch, and military sexual trauma (MST). Results: In our sample, 109 (29%) female veterans reported experiencing childhood abuse. After adjusting for age, race, military branch, childhood sexual abuse, and MST, childhood physical abuse was predictive of poorer physical health, and greater depressive and post-traumatic stress disorder symptoms. No significant association was found between childhood sexual abuse and poor physical or mental health status. After adjusting for other factors, childhood physical abuse was associated with more frequent use of medical health care. Childhood sexual abuse was not a predictor for health care use. Conclusions: Childhood physical abuse remains an important contributor to physical health and mental health, even after adjusting for the more proximate experience of MST. Screening for adverse childhood experiences may facilitate access to appropriate physical and mental health treatment among female veterans. C1 [Mercado, Rowena C.] VA Boston Healthcare Syst, Harvard South Shore Psychiat Residency Training P, Brockton, MA 02301 USA. [Mercado, Rowena C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Wiltsey-Stirman, Shannon; Iverson, Katherine M.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Wiltsey-Stirman, Shannon; Iverson, Katherine M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Mercado, RC (reprint author), VA Boston Healthcare Syst, Harvard South Shore Psychiat Residency Training P, 940 Belmont St, Brockton, MA 02301 USA. OI Wiltsey Stirman, Shannon/0000-0001-9917-5078 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D), Dr. Katherine M. Iverson's Career Development Award [CDA 10-029] FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) as part of Dr. Katherine M. Iverson's Career Development Award (CDA 10-029). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. Government. NR 63 TC 1 Z9 1 U1 5 U2 10 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD OCT PY 2015 VL 180 IS 10 BP 1065 EP 1074 DI 10.7205/MILMED-D-14-00719 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CV9UP UT WOS:000364632900018 PM 26444469 ER PT J AU Altshuler, DM Durbin, RM Abecasis, GR Bentley, DR Chakravarti, A Clark, AG Donnelly, P Eichler, EE Flicek, P Gabriel, SB Gibbs, RA Green, ED Hurles, ME Knoppers, BM Korbel, JO Lander, ES Lee, C Lehrach, H Mardis, ER Marth, GT McVean, GA Nickerson, DA Schmidt, JP Sherry, ST Wang, J Wilson, RK Gibbs, RA Boerwinkle, E Doddapaneni, H Han, Y Korchina, V Kovar, C Lee, S Muzny, D Reid, JG Zhu, YM Wang, J Chang, YQ Feng, Q Fang, XD Guo, XS Jian, M Jiang, H Jin, X Lan, TM Li, GQ Li, JX Li, YR Liu, SM Liu, X Lu, Y Ma, XD Tang, MF Wang, B Wang, GB Wu, HL Wu, RH Xu, X Yin, Y Zhang, DD Zhang, WW Zhao, J Zhao, MR Zheng, XL Lander, ES Altshuler, DM Gabriel, SB Gupta, N Gharani, N Toji, LH Gerry, NP Resch, AM Flicek, P Barker, J Clarke, L Gil, L Hunt, SE Kelman, G Kulesha, E Leinonen, R McLaren, WM Radhakrishnan, R Roa, A Smirnov, D Smith, RE Streeter, I Thormann, A Toneva, I Vaughan, B Zheng-Bradley, X Bentley, DR Grocock, R Humphray, S James, T Kingsbury, Z Lehrach, H Sudbrak, R Albrecht, MW Amstislavskiy, VS Borodina, TA Lienhard, M Mertes, F Sultan, M Timmermann, B Yaspo, ML Mardis, ER Wilson, RK Fulton, L Fulton, R Sherry, ST Ananiev, V Belaia, Z Beloslyudtsev, D Bouk, N Chen, C Church, D Cohen, R Cook, C Garner, J Hefferon, T Kimelman, M Liu, CL Lopez, J Meric, P O'Sullivan, C Ostapchuk, Y Phan, L Ponomarov, S Schneider, V Shekhtman, E Sirotkin, K Slotta, D Zhang, H McVean, GA Durbin, RM Balasubramaniam, S Burton, J Danecek, P Keane, TM Kolb-Kokocinski, A McCarthy, S Stalker, J Quail, M Schmidt, JP Davies, CJ Gollub, J Webster, T Wong, B Zhan, YP Auton, A Campbell, CL Kong, Y Marcketta, A Gibbs, RA Yu, FL Antunes, L Bainbridge, M Muzny, D Sabo, A Huang, ZY Wang, J Coin, LJM Fang, L Guo, XS Jin, X Li, GQ Li, QB Li, YR Li, ZY Lin, HX Liu, BH Luo, RB Shao, HJ Xie, YL Ye, C Yu, C Zhang, F Zheng, HC Zhu, HM Alkan, C Dal, E Kahveci, F Marth, GT Garrison, EP Kural, D Lee, WP Leong, WF Stromberg, M Ward, AN Wu, JT Zhang, MY Daly, MJ DePristo, MA Handsaker, RE Altshuler, DM Banks, E Bhatia, G del Angel, G Gabriel, SB Genovese, G Gupta, N Li, H Kashin, S Lander, ES McCarroll, SA Nemesh, JC Poplin, RE Yoon, SC Lihm, J Makarov, V Clark, AG Gottipati, S Keinan, A Rodriguez-Flores, JL Korbel, JO Rausch, T Fritz, MH Stuetz, AM Flicek, P Beal, K Clarke, L Datta, A Herrero, J McLaren, WM Ritchie, GRS Smith, RE Zerbino, D Zheng-Bradley, X Sabeti, PC Shlyakhter, I Schaffner, SF Vitti, J Cooper, DN Ball, EV Stenson, PD Bentley, DR Barnes, B Bauer, M Cheetham, RK Cox, A Eberle, M Humphray, S Kahn, S Murray, L Peden, J Shaw, R Kenny, EE Batzer, MA Konkel, MK Walker, JA MacArthur, DG Lek, M Sudbrak, R Amstislavskiy, VS Herwig, R Mardis, ER Ding, L Koboldt, DC Larson, D Ye, K Gravel, S Swaroop, A Chew, E Lappalainen, T Erlich, Y Gymrek, M Willems, TF Simpson, JT Shriver, MD Rosenfeld, JA Bustamante, CD Montgomery, SB De La Vega, FM Byrnes, JK Carroll, AW DeGorter, MK Lacroute, P Maples, BK Martin, AR Moreno-Estrada, A Shringarpure, SS Zakharia, F Halperin, E Baran, Y Lee, C Cerveira, E Hwang, J Malhotra, A Plewczynski, D Radew, K Romanovitch, M Zhang, CS Hyland, FCL Craig, DW Christoforides, A Homer, N Izatt, T Kurdoglu, AA Sinari, SA Squire, K Sherry, ST Xiao, CL Sebat, J Antaki, D Gujral, M Noor, A Ye, K Burchard, EG Hernandez, RD Gignoux, CR Haussler, D Katzman, SJ Kent, WJ Howie, B Ruiz-Linares, A Dermitzakis, ET Devine, SE Goncalo, RA Kang, HM Kidd, JM Blackwell, T Caron, S Chen, W Emery, S Fritsche, L Fuchsberger, C Jun, G Li, BS Lyons, R Scheller, C Sidore, C Song, SY Sliwerska, E Taliun, D Tan, A Welch, R Wing, MK Zhan, XW Awadalla, P Hodgkinson, A Li, Y Shi, XH Quitadamo, A Lunter, G McVean, GA Marchini, JL Myers, S Churchhouse, C Delaneau, O Gupta-Hinch, A Kretzschmar, W Iqbal, Z Mathieson, I Menelaou, A Rimmer, A Xifara, DK Oleksyk, TK Fu, YX Liu, XM Xiong, MM Jorde, L Witherspoon, D Xing, JC Eichler, EE Browning, BL Browning, SR Hormozdiari, F Sudmant, PH Khurana, E Durbin, RM Hurles, ME Tyler-Smith, C Albers, CA Ayub, Q Balasubramaniam, S Chen, Y Colonna, V Danecek, P Jostins, L Keane, TM McCarthy, S Walter, K Xue, YL Gerstein, MB Abyzov, A Balasubramanian, S Chen, JM Clarke, D Fu, Y Harmanci, AO Jin, M Lee, D Liu, J Mu, XJ Zhang, J Zhang, Y Li, YR Luo, RB Zhu, HM Alkan, C Dal, E Kahveci, F Marth, GT Garrison, EP Kural, D Lee, WP Ward, AN Wu, JT Zhang, MY McCarroll, SA Handsaker, RE Altshuler, DM Banks, E Del Angel, G Genovese, G Hartl, C Li, H Kashin, S Nemesh, JC Shakir, K Yoon, SC Lihm, J Makarov, V Degenhardt, J Korbel, JO Fritz, MH Meiers, S Raeder, B Rausch, T Stuetz, AM Flicek, P Casale, FP Clarke, L Smith, RE Stegle, O Zheng-Bradley, X Bentley, DR Barnes, B Cheetham, RK Eberle, M Humphray, S Kahn, S Murray, L Shaw, R Lameijer, EW Batzer, MA Konkel, MK Walker, JA Ding, L Hall, I Ye, K Lacroute, P Lee, C Cerveira, E Malhotra, A Hwang, J Plewczynski, D Radew, K Romanovitch, M Zhang, CS Craig, DW Homer, N Church, D Xiao, CL Sebat, J Antaki, D Bafna, V Michaelson, J Ye, K Devine, SE Gardner, EJ Abecasis, GR Kidd, JM Mills, RE Dayama, G Emery, S Jun, G Shi, XH Quitadamo, A Lunter, G McVean, GA Chen, K Fan, X Chong, ZC Chen, TH Witherspoon, D Xing, JC Eichler, EE Chaisson, MJ Hormozdiari, F Huddleston, J Malig, M Nelson, BJ Sudmant, PH Parrish, NF Khurana, E Hurles, ME Ben Blackburne, Lindsay, SJ Ning, ZM Walter, K Zhang, YJ Gerstein, MB Abyzov, A Chen, JM Clarke, D Lam, H Mu, XJ Sisu, C Zhang, J Zhang, Y Gibbs, RA Yu, FL Bainbridge, M Challis, D Evani, US Kovar, C Lu, J Muzny, D Nagaswamy, U Reid, JG Sabo, A Yu, J Guo, XS Li, WS Li, YR Wu, RH Marth, GT Garrison, EP Leong, WF Ward, AN del Angel, G DePristo, MA Gabriel, SB Gupta, N Hartl, C Poplin, RE Clark, AG Rodriguez-Flores, JL Flicek, P Clarke, L Smith, RE Zheng-Bradley, X MacArthur, DG Mardis, ER Fulton, R Koboldt, DC Gravel, S Bustamante, CD Craig, DW Christoforides, A Homer, N Izatt, T Sherry, ST Xiao, CL Dermitzakis, ET Abecasis, GR Kang, HM McVean, GA Gerstein, MB Balasubramanian, S Habegger, L Yu, HY Flicek, P Clarke, L Cunningham, F Dunham, I Zerbino, D Zheng-Bradley, X Lage, K Jespersen, JB Horn, H Montgomery, SB DeGorter, MK Khurana, E Tyler-Smith, C Chen, Y Colonna, V Xue, YL Gerstein, MB Balasubramanian, S Fu, Y Kim, D Auton, A Marcketta, A Desalle, R Narechania, A Sayres, MAW Garrison, EP Handsaker, RE Kashin, S McCarroll, SA Rodriguez-Flores, JL Flicek, P Clarke, L Zheng-Bradley, X Erlich, Y Gymrek, M Willems, TF Bustamante, CD Mendez, FL Poznik, GD Underhill, PA Lee, C Cerveira, E Malhotra, A Romanovitch, M Zhang, CS Abecasis, GR Coin, L Shao, HJ Mittelman, D Tyler-Smith, C Ayub, Q Banerjee, R Cerezo, M Chen, Y Fitzgerald, T Louzada, S Massaia, A McCarthy, S Ritchie, GR Xue, YL Yang, FT Gibbs, RA Kovar, C Kalra, D Hale, W Muzny, D Reid, JG Wang, J Dan, X Guo, XS Li, GQ Li, YR Ye, C Zheng, XL Altshuler, DM Flicek, P Clarke, L Zheng-Bradley, X Bentley, DR Cox, A Humphray, S Kahn, S Sudbrak, R Albrecht, MW Lienhard, M Larson, D Craig, DW Izatt, T Kurdoglu, AA Sherry, ST Xiao, CL Haussler, D Abecasis, GR McVean, GA Durbin, RM Balasubramaniam, S Keane, TM McCarthy, S Stalker, J Chakravarti, A Knoppers, BM Abecasis, GR Barnes, KC Beiswanger, C Burchard, EG Bustamante, CD Cai, HY Cao, HZ Durbin, RM Gerry, NP Gharani, N Gibbs, RA Gignoux, CR Gravel, S Henn, B Jones, D Jorde, L Kaye, JS Keinan, A Kent, A Kerasidou, A Li, YR Mathias, R McVean, GA Moreno-Estrada, A Ossorio, PN Parker, M Resch, AM Rotimi, CN Royal, CD Sandoval, K Su, YY Sudbrak, R Tian, ZM Tishkoff, S Toji, LH Tyler-Smith, C Via, M Wang, YH Yang, HM Yang, L Zhu, JY Bodmer, W Bedoya, G Ruiz-Linares, A Cai, ZM Gao, Y Chu, JY Peltonen, L Garcia-Montero, A Orfao, A Dutil, J Martinez-Cruzado, JC Oleksyk, TK Barnes, KC Mathias, RA Hennis, A Watson, H McKenzie, C Qadri, F LaRocque, R Sabeti, PC Zhu, JY Deng, XY Sabeti, PC Asogun, D Folarin, O Happi, C Omoniwa, O Stremlau, M Tariyal, R Jallow, M Joof, FS Corrah, T Rockett, K Kwiatkowski, D Kooner, J Hien, TT Dunstan, SJ Hang, NT Fonnie, R Garry, R Kanneh, L Moses, L Sabeti, PC Schieffelin, J Grant, DS Gallo, C Poletti, G Saleheen, D Rasheed, A Brook, LD Felsenfeld, A McEwen, JE Vaydylevich, Y Green, ED Duncanson, A Dunn, M Schloss, JA Wang, J Yang, HM Auton, A Brooks, LD Durbin, RM Garrison, EP Kang, HM Korbel, JO Marchini, JL McCarthy, S McVean, GA Abecasis, GR AF Altshuler, David M. Durbin, Richard M. Abecasis, Goncalo R. Bentley, David R. Chakravarti, Aravinda Clark, Andrew G. Donnelly, Peter Eichler, Evan E. Flicek, Paul Gabriel, Stacey B. Gibbs, Richard A. Green, Eric D. Hurles, Matthew E. Knoppers, Bartha M. Korbel, Jan O. Lander, Eric S. Lee, Charles Lehrach, Hans Mardis, Elaine R. Marth, Gabor T. McVean, Gil A. Nickerson, Deborah A. Schmidt, Jeanette P. Sherry, Stephen T. Wang, Jun Wilson, Richard K. Gibbs, Richard A. Boerwinkle, Eric Doddapaneni, Harsha Han, Yi Korchina, Viktoriya Kovar, Christie Lee, Sandra Muzny, Donna Reid, Jeffrey G. Zhu, Yiming Wang, Jun Chang, Yuqi Feng, Qiang Fang, Xiaodong Guo, Xiaosen Jian, Min Jiang, Hui Jin, Xin Lan, Tianming Li, Guoqing Li, Jingxiang Li, Yingrui Liu, Shengmao Liu, Xiao Lu, Yao Ma, Xuedi Tang, Meifang Wang, Bo Wang, Guangbiao Wu, Honglong Wu, Renhua Xu, Xun Yin, Ye Zhang, Dandan Zhang, Wenwei Zhao, Jiao Zhao, Meiru Zheng, Xiaole Lander, Eric S. Altshuler, David M. Gabriel, Stacey B. Gupta, Namrata Gharani, Neda Toji, Lorraine H. Gerry, Norman P. Resch, Alissa M. Flicek, Paul Barker, Jonathan Clarke, Laura Gil, Laurent Hunt, Sarah E. Kelman, Gavin Kulesha, Eugene Leinonen, Rasko McLaren, William M. Radhakrishnan, Rajesh Roa, Asier Smirnov, Dmitriy Smith, Richard E. Streeter, Ian Thormann, Anja Toneva, Iliana Vaughan, Brendan Zheng-Bradley, Xiangqun Bentley, David R. Grocock, Russell Humphray, Sean James, Terena Kingsbury, Zoya Lehrach, Hans Sudbrak, Ralf Albrecht, Marcus W. Amstislavskiy, Vyacheslav S. Borodina, Tatiana A. Lienhard, Matthias Mertes, Florian Sultan, Marc Timmermann, Bernd Yaspo, Marie-Laure Mardis, Elaine R. Wilson, Richard K. Fulton, Lucinda Fulton, Robert Sherry, Stephen T. Ananiev, Victor Belaia, Zinaida Beloslyudtsev, Dimitriy Bouk, Nathan Chen, Chao Church, Deanna Cohen, Robert Cook, Charles Garner, John Hefferon, Timothy Kimelman, Mikhail Liu, Chunlei Lopez, John Meric, Peter O'Sullivan, Chris Ostapchuk, Yuri Phan, Lon Ponomarov, Sergiy Schneider, Valerie Shekhtman, Eugene Sirotkin, Karl Slotta, Douglas Zhang, Hua McVean, Gil A. Durbin, Richard M. Balasubramaniam, Senduran Burton, John Danecek, Petr Keane, Thomas M. Kolb-Kokocinski, Anja McCarthy, Shane Stalker, James Quail, Michael Schmidt, Jeanette P. Davies, Christopher J. Gollub, Jeremy Webster, Teresa Wong, Brant Zhan, Yiping Auton, Adam Campbell, Christopher L. Kong, Yu Marcketta, Anthony Gibbs, Richard A. Yu, Fuli Antunes, Lilian Bainbridge, Matthew Muzny, Donna Sabo, Aniko Huang, Zhuoyi Wang, Jun Coin, Lachlan J. M. Fang, Lin Guo, Xiaosen Jin, Xin Li, Guoqing Li, Qibin Li, Yingrui Li, Zhenyu Lin, Haoxiang Liu, Binghang Luo, Ruibang Shao, Haojing Xie, Yinlong Ye, Chen Yu, Chang Zhang, Fan Zheng, Hancheng Zhu, Hongmei Alkan, Can Dal, Elif Kahveci, Fatma Marth, Gabor T. Garrison, Erik P. Kural, Deniz Lee, Wan-Ping Leong, Wen Fung Stromberg, Michael Ward, Alistair N. Wu, Jiantao Zhang, Mengyao Daly, Mark J. DePristo, Mark A. Handsaker, Robert E. Altshuler, David M. Banks, Eric Bhatia, Gaurav del Angel, Guillermo Gabriel, Stacey B. Genovese, Giulio Gupta, Namrata Li, Heng Kashin, Seva Lander, Eric S. McCarroll, Steven A. Nemesh, James C. Poplin, Ryan E. Yoon, Seungtai C. Lihm, Jayon Makarov, Vladimir Clark, Andrew G. Gottipati, Srikanth Keinan, Alon Rodriguez-Flores, Juan L. Korbel, Jan O. Rausch, Tobias Fritz, Markus H. Stuetz, Adrian M. Flicek, Paul Beal, Kathryn Clarke, Laura Datta, Avik Herrero, Javier McLaren, William M. Ritchie, Graham R. S. Smith, Richard E. Zerbino, Daniel Zheng-Bradley, Xiangqun Sabeti, Pardis C. Shlyakhter, Ilya Schaffner, Stephen F. Vitti, Joseph Cooper, David N. Ball, Edward V. Stenson, Peter D. Bentley, David R. Barnes, Bret Bauer, Markus Cheetham, R. Keira Cox, Anthony Eberle, Michael Humphray, Sean Kahn, Scott Murray, Lisa Peden, John Shaw, Richard Kenny, Eimear E. Batzer, Mark A. Konkel, Miriam K. Walker, Jerilyn A. MacArthur, Daniel G. Lek, Monkol Sudbrak, Ralf Amstislavskiy, Vyacheslav S. Herwig, Ralf Mardis, Elaine R. Ding, Li Koboldt, Daniel C. Larson, David Ye, Kai Gravel, Simon Swaroop, Anand Chew, Emily Lappalainen, Tuuli Erlich, Yaniv Gymrek, Melissa Willems, Thomas Frederick Simpson, Jared T. Shriver, Mark D. Rosenfeld, Jeffrey A. Bustamante, Carlos D. Montgomery, Stephen B. De La Vega, Francisco M. Byrnes, Jake K. Carroll, Andrew W. DeGorter, Marianne K. Lacroute, Phil Maples, Brian K. Martin, Alicia R. Moreno-Estrada, Andres Shringarpure, Suyash S. Zakharia, Fouad Halperin, Eran Baran, Yael Lee, Charles Cerveira, Eliza Hwang, Jaeho Malhotra, Ankit Plewczynski, Dariusz Radew, Kamen Romanovitch, Mallory Zhang, Chengsheng Hyland, Fiona C. L. Craig, David W. Christoforides, Alexis Homer, Nils Izatt, Tyler Kurdoglu, Ahmet A. Sinari, Shripad A. Squire, Kevin Sherry, Stephen T. Xiao, Chunlin Sebat, Jonathan Antaki, Danny Gujral, Madhusudan Noor, Amina Ye, Kenny Burchard, Esteban G. Hernandez, Ryan D. Gignoux, Christopher R. Haussler, David Katzman, Sol J. Kent, W. James Howie, Bryan Ruiz-Linares, Andres Dermitzakis, Emmanouil T. Devine, Scott E. Goncalo, R. Abecasis Kang, Hyun Min Kidd, Jeffrey M. Blackwell, Tom Caron, Sean Chen, Wei Emery, Sarah Fritsche, Lars Fuchsberger, Christian Jun, Goo Li, Bingshan Lyons, Robert Scheller, Chris Sidore, Carlo Song, Shiya Sliwerska, Elzbieta Taliun, Daniel Tan, Adrian Welch, Ryan Wing, Mary Kate Zhan, Xiaowei Awadalla, Philip Hodgkinson, Alan Li, Yun Shi, Xinghua Quitadamo, Andrew Lunter, Gerton McVean, Gil A. Marchini, Jonathan L. Myers, Simon Churchhouse, Claire Delaneau, Olivier Gupta-Hinch, Anjali Kretzschmar, Warren Iqbal, Zamin Mathieson, Iain Menelaou, Androniki Rimmer, Andy Xifara, Dionysia K. Oleksyk, Taras K. Fu, Yunxin Liu, Xiaoming Xiong, Momiao Jorde, Lynn Witherspoon, David Xing, Jinchuan Eichler, Evan E. Browning, Brian L. Browning, Sharon R. Hormozdiari, Fereydoun Sudmant, Peter H. Khurana, Ekta Durbin, Richard M. Hurles, Matthew E. Tyler-Smith, Chris Albers, Cornelis A. Ayub, Qasim Balasubramaniam, Senduran Chen, Yuan Colonna, Vincenza Danecek, Petr Jostins, Luke Keane, Thomas M. McCarthy, Shane Walter, Klaudia Xue, Yali Gerstein, Mark B. Abyzov, Alexej Balasubramanian, Suganthi Chen, Jieming Clarke, Declan Fu, Yao Harmanci, Arif O. Jin, Mike Lee, Donghoon Liu, Jeremy Mu, Xinmeng Jasmine Zhang, Jing Zhang, Yan Li, Yingrui Luo, Ruibang Zhu, Hongmei Alkan, Can Dal, Elif Kahveci, Fatma Marth, Gabor T. Garrison, Erik P. Kural, Deniz Lee, Wan-Ping Ward, Alistair N. Wu, Jiantao Zhang, Mengyao McCarroll, Steven A. Handsaker, Robert E. Altshuler, David M. Banks, Eric Del Angel, Guillermo Genovese, Giulio Hartl, Chris Li, Heng Kashin, Seva Nemesh, James C. Shakir, Khalid Yoon, Seungtai C. Lihm, Jayon Makarov, Vladimir Degenhardt, Jeremiah Korbel, Jan O. Fritz, Markus H. Meiers, Sascha Raeder, Benjamin Rausch, Tobias Stuetz, Adrian M. Flicek, Paul Casale, Francesco Paolo Clarke, Laura Smith, Richard E. Stegle, Oliver Zheng-Bradley, Xiangqun Bentley, David R. Barnes, Bret Cheetham, R. Keira Eberle, Michael Humphray, Sean Kahn, Scott Murray, Lisa Shaw, Richard Lameijer, Eric-Wubbo Batzer, Mark A. Konkel, Miriam K. Walker, Jerilyn A. Ding, Li Hall, Ira Ye, Kai Lacroute, Phil Lee, Charles Cerveira, Eliza Malhotra, Ankit Hwang, Jaeho Plewczynski, Dariusz Radew, Kamen Romanovitch, Mallory Zhang, Chengsheng Craig, David W. Homer, Nils Church, Deanna Xiao, Chunlin Sebat, Jonathan Antaki, Danny Bafna, Vineet Michaelson, Jacob Ye, Kenny Devine, Scott E. Gardner, Eugene J. Abecasis, Goncalo R. Kidd, Jeffrey M. Mills, Ryan E. Dayama, Gargi Emery, Sarah Jun, Goo Shi, Xinghua Quitadamo, Andrew Lunter, Gerton McVean, Gil A. Chen, Ken Fan, Xian Chong, Zechen Chen, Tenghui Witherspoon, David Xing, Jinchuan Eichler, Evan E. Chaisson, Mark J. Hormozdiari, Fereydoun Huddleston, John Malig, Maika Nelson, Bradley J. Sudmant, Peter H. Parrish, Nicholas F. Khurana, Ekta Hurles, Matthew E. Blackburne, Ben Lindsay, Sarah J. Ning, Zemin Walter, Klaudia Zhang, Yujun Gerstein, Mark B. Abyzov, Alexej Chen, Jieming Clarke, Declan Lam, Hugo Mu, Xinmeng Jasmine Sisu, Cristina Zhang, Jing Zhang, Yan Gibbs, Richard A. Yu, Fuli Bainbridge, Matthew Challis, Danny Evani, Uday S. Kovar, Christie Lu, James Muzny, Donna Nagaswamy, Uma Reid, Jeffrey G. Sabo, Aniko Yu, Jin Guo, Xiaosen Li, Wangshen Li, Yingrui Wu, Renhua Marth, Gabor T. Garrison, Erik P. Leong, Wen Fung Ward, Alistair N. del Angel, Guillermo DePristo, Mark A. Gabriel, Stacey B. Gupta, Namrata Hartl, Chris Poplin, Ryan E. Clark, Andrew G. Rodriguez-Flores, Juan L. Flicek, Paul Clarke, Laura Smith, Richard E. Zheng-Bradley, Xiangqun MacArthur, Daniel G. Mardis, Elaine R. Fulton, Robert Koboldt, Daniel C. Gravel, Simon Bustamante, Carlos D. Craig, David W. Christoforides, Alexis Homer, Nils Izatt, Tyler Sherry, Stephen T. Xiao, Chunlin Dermitzakis, Emmanouil T. Abecasis, Gonalo R. Kang, Hyun Min McVean, Gil A. Gerstein, Mark B. Balasubramanian, Suganthi Habegger, Lukas Yu, Haiyuan Flicek, Paul Clarke, Laura Cunningham, Fiona Dunham, Ian Zerbino, Daniel Zheng-Bradley, Xiangqun Lage, Kasper Jespersen, Jakob Berg Horn, Heiko Montgomery, Stephen B. DeGorter, Marianne K. Khurana, Ekta Tyler-Smith, Chris Chen, Yuan Colonna, Vincenza Xue, Yali Gerstein, Mark B. Balasubramanian, Suganthi Fu, Yao Kim, Donghoon Auton, Adam Marcketta, Anthony Desalle, Rob Narechania, Apurva Sayres, Melissa A. Wilson Garrison, Erik P. Handsaker, Robert E. Kashin, Seva McCarroll, Steven A. Rodriguez-Flores, Juan L. Flicek, Paul Clarke, Laura Zheng-Bradley, Xiangqun Erlich, Yaniv Gymrek, Melissa Willems, Thomas Frederick Bustamante, Carlos D. Mendez, Fernando L. Poznik, G. David Underhill, Peter A. Lee, Charles Cerveira, Eliza Malhotra, Ankit Romanovitch, Mallory Zhang, Chengsheng Abecasis, Goncalo R. Coin, Lachlan Shao, Haojing Mittelman, David Tyler-Smith, Chris Ayub, Qasim Banerjee, Ruby Cerezo, Maria Chen, Yuan Fitzgerald, ThomasW. Louzada, Sandra Massaia, Andrea McCarthy, Shane Ritchie, Graham R. Xue, Yali Yang, Fengtang Gibbs, Richard A. Kovar, Christie Kalra, Divya Hale, Walker Muzny, Donna Reid, Jeffrey G. Wang, Jun Dan, Xu Guo, Xiaosen Li, Guoqing Li, Yingrui Ye, Chen Zheng, Xiaole Altshuler, David M. Flicek, Paul Clarke, Laura Zheng-Bradley, Xiangqun Bentley, David R. Cox, Anthony Humphray, Sean Kahn, Scott Sudbrak, Ralf Albrecht, Marcus W. Lienhard, Matthias Larson, David Craig, David W. Izatt, Tyler Kurdoglu, Ahmet A. Sherry, Stephen T. Xiao, Chunlin Haussler, David Abecasis, Goncalo R. McVean, Gil A. Durbin, Richard M. Balasubramaniam, Senduran Keane, Thomas M. McCarthy, Shane Stalker, James Chakravarti, Aravinda Knoppers, Bartha M. Abecasis, Goncalo R. Barnes, Kathleen C. Beiswanger, Christine Burchard, Esteban G. Bustamante, Carlos D. Cai, Hongyu Cao, Hongzhi Durbin, Richard M. Gerry, Norman P. Gharani, Neda Gibbs, Richard A. Gignoux, Christopher R. Gravel, Simon Henn, Brenna Jones, Danielle Jorde, Lynn Kaye, Jane S. Keinan, Alon Kent, Alastair Kerasidou, Angeliki Li, Yingrui Mathias, Rasika McVean, Gil A. Moreno-Estrada, Andres Ossorio, Pilar N. Parker, Michael Resch, Alissa M. Rotimi, Charles N. Royal, Charmaine D. Sandoval, Karla Su, Yeyang Sudbrak, Ralf Tian, Zhongming Tishkoff, Sarah Toji, Lorraine H. Tyler-Smith, Chris Via, Marc Wang, Yuhong Yang, Huanming Yang, Ling Zhu, Jiayong Bodmer, Walter Bedoya, Gabriel Ruiz-Linares, Andres Cai, Zhiming Gao, Yang Chu, Jiayou Peltonen, Leena Garcia-Montero, Andres Orfao, Alberto Dutil, Julie Martinez-Cruzado, Juan C. Oleksyk, Taras K. Barnes, Kathleen C. Mathias, Rasika A. Hennis, Anselm Watson, Harold McKenzie, Colin Qadri, Firdausi LaRocque, Regina Sabeti, Pardis C. Zhu, Jiayong Deng, Xiaoyan Sabeti, Pardis C. Asogun, Danny Folarin, Onikepe Happi, Christian Omoniwa, Omonwunmi Stremlau, Matt Tariyal, Ridhi Jallow, Muminatou Joof, Fatoumatta Sisay Corrah, Tumani Rockett, Kirk Kwiatkowski, Dominic Kooner, Jaspal Tran Tinh Hien Dunstan, Sarah J. Nguyen Thuy Hang Fonnie, Richard Garry, Robert Kanneh, Lansana Moses, Lina Sabeti, Pardis C. Schieffelin, John Grant, Donald S. Gallo, Carla Poletti, Giovanni Saleheen, Danish Rasheed, Asif Brook, Lisa D. Felsenfeld, Adaml. McEwen, Jean E. Vaydylevich, Yekaterina Green, Eric D. Duncanson, Audrey Dunn, Michael Schloss, Jeffery A. Wang, Jun Yang, Huanming Auton, Adam Brooks, Lisa D. Durbin, Richard M. Garrison, Erik P. Kang, Hyun Min Korbel, Jan O. Marchini, Jonathan L. McCarthy, Shane McVean, Gil A. Abecasis, Goncalo R. CA Genomes Project Consortium TI A global reference for human genetic variation SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; COMPLEMENT FACTOR-H; MACULAR DEGENERATION; POPULATION HISTORY; BAYES FACTORS; MUTATION; DISEASE; VARIANT; SUSCEPTIBILITY; INDIVIDUALS AB The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. C1 [Auton, Adam; Campbell, Christopher L.; Kong, Yu; Marcketta, Anthony; Auton, Adam; Marcketta, Anthony; Auton, Adam] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. [Abecasis, Goncalo R.; Goncalo, R. Abecasis; Kang, Hyun Min; Blackwell, Tom; Caron, Sean; Fritsche, Lars; Fuchsberger, Christian; Jun, Goo; Scheller, Chris; Sidore, Carlo; Taliun, Daniel; Tan, Adrian; Welch, Ryan; Wing, Mary Kate; Jun, Goo; Abecasis, Gonalo R.] Univ Michigan, Ctr Stat Genet, Biostat, Ann Arbor, MI 48109 USA. [Altshuler, David M.] Vertex Pharmaceut, Boston, MA 02210 USA. [Durbin, Richard M.; Hurles, Matthew E.; Balasubramaniam, Senduran; Burton, John; Danecek, Petr; Keane, Thomas M.; Kolb-Kokocinski, Anja; McCarthy, Shane; Stalker, James; Quail, Michael; Garrison, Erik P.; Tyler-Smith, Chris; Ayub, Qasim; Chen, Yuan; Colonna, Vincenza; Walter, Klaudia; Xue, Yali; Garrison, Erik P.; Blackburne, Ben; Lindsay, Sarah J.; Ning, Zemin; Zhang, Yujun; Banerjee, Ruby; Cerezo, Maria; Fitzgerald, ThomasW.; Louzada, Sandra; Massaia, Andrea; Ritchie, Graham R.; Yang, Fengtang] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Bentley, David R.; Grocock, Russell; Humphray, Sean; James, Terena; Kingsbury, Zoya; Bauer, Markus; Cheetham, R. Keira; Cox, Anthony; Eberle, Michael; Murray, Lisa; Peden, John; Shaw, Richard] Illumina United Kingdom, Saffron Walden CB10 1XL, Essex, England. [Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Clark, Andrew G.; Clark, Andrew G.; Keinan, Alon; Degenhardt, Jeremiah] Cornell Univ, Ctr Comparat & Populat Genom, Ithaca, NY 14850 USA. [Donnelly, Peter; McVean, Gil A.; McVean, Gil A.; Lunter, Gerton; Marchini, Jonathan L.; Myers, Simon; Gupta-Hinch, Anjali; Kretzschmar, Warren; Iqbal, Zamin; Mathieson, Iain; Xifara, Dionysia K.; Jostins, Luke; Jallow, Muminatou; Joof, Fatoumatta Sisay; Corrah, Tumani; Rockett, Kirk; Kwiatkowski, Dominic] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Donnelly, Peter; McVean, Gil A.; Marchini, Jonathan L.; Myers, Simon; Churchhouse, Claire; Delaneau, Olivier; Menelaou, Androniki; Xifara, Dionysia K.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Eichler, Evan E.; Nickerson, Deborah A.; Hormozdiari, Fereydoun; Sudmant, Peter H.; Chaisson, Mark J.; Huddleston, John; Malig, Maika; Nelson, Bradley J.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Eichler, Evan E.; Huddleston, John] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Flicek, Paul; Korbel, Jan O.; Barker, Jonathan; Clarke, Laura; Gil, Laurent; Hunt, Sarah E.; Kelman, Gavin; Kulesha, Eugene; Leinonen, Rasko; McLaren, William M.; Radhakrishnan, Rajesh; Roa, Asier; Smirnov, Dmitriy; Smith, Richard E.; Streeter, Ian; Thormann, Anja; Toneva, Iliana; Vaughan, Brendan; Zheng-Bradley, Xiangqun; Beal, Kathryn; Datta, Avik; Ritchie, Graham R. S.; Zerbino, Daniel; Casale, Francesco Paolo; Stegle, Oliver; Cunningham, Fiona; Dunham, Ian] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. [Gabriel, Stacey B.; Lander, Eric S.; Gupta, Namrata; Daly, Mark J.; Handsaker, Robert E.; Banks, Eric; Bhatia, Gaurav; del Angel, Guillermo; Genovese, Giulio; Li, Heng; Kashin, Seva; McCarroll, Steven A.; Nemesh, James C.; Poplin, Ryan E.; Sabeti, Pardis C.; Shlyakhter, Ilya; Schaffner, Stephen F.; Vitti, Joseph; Gymrek, Melissa; Mu, Xinmeng Jasmine; Hartl, Chris; Shakir, Khalid; Poplin, Ryan E.; Lage, Kasper; Jespersen, Jakob Berg; Horn, Heiko; Stremlau, Matt; Tariyal, Ridhi] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Gibbs, Richard A.; Boerwinkle, Eric; Doddapaneni, Harsha; Han, Yi; Korchina, Viktoriya; Kovar, Christie; Lee, Sandra; Muzny, Donna; Reid, Jeffrey G.; Zhu, Yiming; Yu, Fuli; Antunes, Lilian; Bainbridge, Matthew; Sabo, Aniko; Huang, Zhuoyi; Challis, Danny; Evani, Uday S.; Lu, James; Nagaswamy, Uma; Yu, Jin; Kalra, Divya; Hale, Walker] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Green, Eric D.; Green, Eric D.] NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Knoppers, Bartha M.] McGill Univ, Ctr Genom & Policy, Montreal, PQ H3A 1A4, Canada. [Rausch, Tobias; Stuetz, Adrian M.; Meiers, Sascha; Raeder, Benjamin] European Mol Biol Lab, Genome Biol Res Unit, Heidelberg, Germany. [Lee, Charles; Cerveira, Eliza; Hwang, Jaeho; Malhotra, Ankit; Plewczynski, Dariusz; Radew, Kamen; Romanovitch, Mallory; Zhang, Chengsheng] Jackson Lab Genom Med, Farmington, CT 06032 USA. [Lee, Charles] Ewha Womans Univ, Dept Life Sci, Seoul 120750, South Korea. [Lehrach, Hans; Amstislavskiy, Vyacheslav S.; Lienhard, Matthias; Mertes, Florian; Sultan, Marc; Timmermann, Bernd; Yaspo, Marie-Laure; Herwig, Ralf] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Lehrach, Hans] Dahlem Ctr Genome Res & Med Syst Biol, D-14195 Berlin, Germany. [Mardis, Elaine R.; Wilson, Richard K.; Mardis, Elaine R.; Fulton, Lucinda; Fulton, Robert; Ding, Li; Koboldt, Daniel C.; Larson, David; Ye, Kai; Hall, Ira] Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO 63108 USA. [Marth, Gabor T.; Ward, Alistair N.; Wu, Jiantao; Zhang, Mengyao; Leong, Wen Fung] Univ Utah, Sch Med, USTAR Ctr Genet Discovery, Salt Lake City, UT 84112 USA. [Marth, Gabor T.; Ward, Alistair N.; Wu, Jiantao; Zhang, Mengyao; Leong, Wen Fung] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84112 USA. [Schmidt, Jeanette P.; Davies, Christopher J.; Gollub, Jeremy; Webster, Teresa; Wong, Brant; Zhan, Yiping] Affymetrix, Santa Clara, CA 95051 USA. [Sherry, Stephen T.; Ananiev, Victor; Belaia, Zinaida; Beloslyudtsev, Dimitriy; Bouk, Nathan; Chen, Chao; Cohen, Robert; Cook, Charles; Garner, John; Hefferon, Timothy; Kimelman, Mikhail; Liu, Chunlei; Lopez, John; Meric, Peter; Ostapchuk, Yuri; Phan, Lon; Ponomarov, Sergiy; Schneider, Valerie; Shekhtman, Eugene; Sirotkin, Karl; Slotta, Douglas; Zhang, Hua; Xiao, Chunlin] US Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Wang, Jun; Chang, Yuqi; Feng, Qiang; Fang, Xiaodong; Guo, Xiaosen; Jian, Min; Jiang, Hui; Jin, Xin; Lan, Tianming; Li, Guoqing; Li, Jingxiang; Li, Yingrui; Liu, Shengmao; Liu, Xiao; Lu, Yao; Ma, Xuedi; Tang, Meifang; Wang, Bo; Wang, Guangbiao; Wu, Honglong; Wu, Renhua; Xu, Xun; Yin, Ye; Zhang, Dandan; Zhang, Wenwei; Zhao, Jiao; Zhao, Meiru; Zheng, Xiaole; Coin, Lachlan J. M.; Fang, Lin; Guo, Xiaosen; Li, Qibin; Li, Zhenyu; Lin, Haoxiang; Liu, Binghang; Luo, Ruibang; Shao, Haojing; Xie, Yinlong; Ye, Chen; Yu, Chang; Zhang, Fan; Zheng, Hancheng; Zhu, Hongmei; Moreno-Estrada, Andres; Li, Wangshen; Dan, Xu; Cai, Hongyu; Cao, Hongzhi; Su, Yeyang; Tian, Zhongming; Wang, Yuhong; Yang, Huanming; Yang, Ling; Zhu, Jiayong; Cai, Zhiming; Yang, Huanming] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Feng, Qiang; Fang, Xiaodong; Jian, Min; Jiang, Hui; Liu, Xiao; Fang, Lin; Cao, Hongzhi] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark. King Abdulaziz Univ, Princess Jawhara Albrahim Ctr Excellence Res Here, Jeddah 80205, Saudi Arabia. Macau Univ Sci & Technol, Taipa 999078, Macau, Peoples R China. Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China. 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[Jespersen, Jakob Berg] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Desalle, Rob] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA. [Narechania, Apurva] Amer Museum Nat Hist, Dept Invertebrate Zool, New York, NY 10024 USA. [Sayres, Melissa A. Wilson] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. [Poznik, G. David] Stanford Univ, Program Biomed Informat, Stanford, CA 94305 USA. [Coin, Lachlan; Shao, Haojing] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia. [Mittelman, David] Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. [Barnes, Kathleen C.] Johns Hopkins Univ, Sch Med, Div Allergy & Clin Immunol, Baltimore, MD 21205 USA. [Henn, Brenna] SUNY Stony Brook, Dept Ecol & Evolut, Stony Brook, NY 11794 USA. [Kaye, Jane S.] Univ Oxford, Lawand Emerging Technol, Ctr Hlth, Oxford OX3 7LF, England. [Kent, Alastair] Genet Alliance, London N1 3QP, England. [Kerasidou, Angeliki; Parker, Michael] Univ Oxford, Ethox Ctr, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England. [Mathias, Rasika; Mathias, Rasika A.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Ossorio, Pilar N.] Univ Wisconsin, Morgridge Inst Res, Dept Med Hist & Bioeth, Madison, WI 53706 USA. [Ossorio, Pilar N.] Univ Wisconsin, Sch Law, Madison, WI 53706 USA. [Rotimi, Charles N.] NHGRI, US Natl Inst Hlth, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Royal, Charmaine D.] Duke Univ, Dept African & African Amer Studies, Durham, NC 27708 USA. [Tishkoff, Sarah] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Via, Marc] Univ Barcelona, Dept Psychiat & Clin Psychobiol, Barcelona 08035, Spain. [Via, Marc] Univ Barcelona, Inst Brain Cognit & Behav IR3C, Barcelona 08035, Spain. [Bodmer, Walter] Univ Oxford, John Radcliffe Hosp, Canc & Immunogenet Lab, Oxford OX3 9DS, England. [Bedoya, Gabriel] Univ Antioquia, Inst Biol, Lab Mol Genet, Medellin, Colombia. 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[Asogun, Danny] Irrua Specialist Teaching Hosp, Edo, Edo State, Nigeria. [Folarin, Onikepe; Happi, Christian; Omoniwa, Omonwunmi] Redeemers Univ, Ede, Ogun State, Nigeria. [Happi, Christian; Omoniwa, Omonwunmi] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Jallow, Muminatou; Joof, Fatoumatta Sisay; Corrah, Tumani; Rockett, Kirk; Kwiatkowski, Dominic] MRC Unit, Banjul, Gambia. [Kooner, Jaspal] Univ London Imperial Coll Sci Technol & Med, NHLI, Hammersmith Hosp, London SW7 2AZ, England. [Tran Tinh Hien; Dunstan, Sarah J.; Nguyen Thuy Hang] Univ Oxford, Clin Res Unit, Ctr Trop Med, Ho Chi Minh City, Vietnam. [Dunstan, Sarah J.] Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic 3000, Australia. [Fonnie, Richard; Kanneh, Lansana; Grant, Donald S.] Kenema Govt Hosp, Minist Hlth & Sanitat, Kenema, Sierra Leone. [Garry, Robert; Moses, Lina; Schieffelin, John; Grant, Donald S.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. [Gallo, Carla; Poletti, Giovanni] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Invest & Desarrollo, Lima, Peru. [Saleheen, Danish; Rasheed, Asif] Ctr Noncommunicable Dis, Karachi, Pakistan. [Saleheen, Danish] Univ Penn, Perelman Sch Med, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Brook, Lisa D.; Felsenfeld, Adaml.; McEwen, Jean E.; Vaydylevich, Yekaterina; Schloss, Jeffery A.; Brooks, Lisa D.] NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Duncanson, Audrey; Dunn, Michael] Wellcome Trust Res Labs, London NW1 2BE, England. [Yang, Huanming] James D Watson Inst Genome Sci, Hangzhou 310008, Zhejiang, Peoples R China. RP Auton, A (reprint author), Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. EM goncalo@umich.edu; adam.auton@gmail.com RI Alkan, Can/D-2982-2009; Schaffner, Stephen/D-1189-2011; Ye, Kai/B-3640-2012; Wang, Jun/C-8434-2016; Browning, Sharon/B-1530-2008; Lunter, Gerton/H-4939-2016; Browning, Brian/A-1178-2010; Li, Heng/D-9344-2011; Coin, Lachlan/A-9001-2014; Mu, Xinmeng/P-2562-2016; Mills, Ryan/A-1979-2011; Kahveci, Fatma/E-1621-2017; Jun, Goo/F-1941-2017; Wang, Jun/B-9503-2016; Myers, Simon/A-6792-2015; Colonna, Vincenza/H-2021-2014; OI Alkan, Can/0000-0002-5443-0706; Wang, Jun/0000-0002-8540-8931; Browning, Sharon/0000-0001-7251-9715; Browning, Brian/0000-0001-6454-6633; Li, Heng/0000-0003-4874-2874; Coin, Lachlan/0000-0002-4300-455X; Mu, Xinmeng/0000-0002-8079-0828; Mills, Ryan/0000-0003-3425-6998; Kahveci, Fatma/0000-0003-3096-1753; Jun, Goo/0000-0003-0891-0204; Sisu, Cristina/0000-0001-9371-0797; Datta, Avik/0000-0002-1411-8638; Fitzgerald, Tomas/0000-0002-2370-8496; Vaughan, Brendan/0000-0002-2199-1267; /0000-0002-6086-3903; Garner, John/0000-0003-0853-0279; Meiers, Sascha/0000-0003-2609-0000; Thormann, Anja/0000-0001-8858-5506; Kretzschmar, Warren/0000-0002-2575-0807; Fuchsberger, Christian/0000-0002-5918-8947; Leinonen, Rasko/0000-0002-2639-7187; Hunt, Sarah/0000-0002-8350-1235; Horn, Heiko/0000-0003-4898-0557; Cooper, David N./0000-0002-8943-8484; Sebat, Jonathan/0000-0002-9087-526X; Zheng Bradley, Xiangqun/0000-0002-9324-2708; Sudmant, Peter/0000-0002-9573-8248; Gil, Laurent/0000-0002-9475-4502; Gerstein, Mark/0000-0002-9746-3719; Lindsay, Sarah/0000-0002-0965-3070; Wang, Jun/0000-0002-2113-5874; Myers, Simon/0000-0002-2585-9626; Lunter, Gerton/0000-0002-3798-2058; Lappalainen, Tuuli/0000-0002-7746-8109; Chen, Tenghui/0000-0003-0683-8974; Chen, Jieming/0000-0003-3767-9486; Colonna, Vincenza/0000-0002-3966-0474; Cerezo Fernandez, Maria/0000-0003-3073-1130; Herrero, Javier/0000-0001-7313-717X; Clarke, Laura/0000-0002-5989-6898; Swaroop, Anand/0000-0002-1975-1141; Flicek, Paul/0000-0002-3897-7955; McLaren, William/0000-0001-6218-1116; Dunham, Ian/0000-0003-2525-5598; Martin, Alicia/0000-0003-0241-3522; McCarthy, Shane/0000-0002-2715-4187; Dunstan, Sarah/0000-0001-7873-933X; Kwiatkowski, Dominic/0000-0002-5023-0176; Raeder, Benjamin/0000-0002-9494-8884; Iqbal, Zamin/0000-0001-8466-7547; Keane, Thomas/0000-0001-7532-6898; Zerbino, Daniel/0000-0001-5350-3056; Stegle, Oliver/0000-0002-8818-7193; Abyzov, Alexej/0000-0001-5405-6729; Via, Marc/0000-0002-9966-9921; Rodriguez-Flores, Juan L/0000-0002-0394-8062; Parrish, Nicholas/0000-0002-6971-8016; Ayub, Qasim/0000-0003-3291-0917; Mendez, Fernando/0000-0002-0879-3813 FU Wellcome Trust [090532/Z/09/Z, 095552/Z/11/Z, WT098051, WT095908, WT109497, WT086084/Z/08/Z, WT100956/Z/13/Z, WT097307, WT0855322/Z/08/Z, WT090770/Z/09/Z, 089276/Z.09/Z]; Medical Research Council UK [G0801823]; UK Biotechnology and Biological Sciences Research Council [BB/I02593X/1, BB/I021213/1]; British Heart Foundation; Monument Trust; European Molecular Biology Laboratory; European Research Council [617306]; Chinese 863 Program [2012AA02A201]; National Basic Research program of China 973 program [2011CB809201, 2011CB809202, 2011CB809203]; Natural Science Foundation of China [31161130357]; Shenzhen Municipal Government of China [ZYC201105170397A]; Canadian Institutes of Health Research [136855]; Canada Research Chair; Le Fonds de Recherche du Quebec-Sante (FRQS); Genome Quebec; Ontario Ministry of Research and Innovation - Ontario Institute for Cancer Research Investigator Award; Quebec Ministry of Economic Development, Innovation, and Exports [PSR-SIIRI-195]; German Federal Ministry of Education and Research (BMBF) [0315428A, 01GS08201]; Max Planck Society; BMBF-EPITREAT [0316190A]; German Research Foundation (Deutsche Forschungsgemeinschaft) [KO4037/1-1]; Beatriu de Pinos Program [2006 BP-A 10144, 2009 BP-B 00274]; Spanish National Institute for Health Research [PRB2 IPT13/0001-ISCIII-SGEFI/FEDER]; Ewha Womans University; Japan Society for the Promotion of Science [PE13075]; Louis Jeantet Foundation; Marie Curie Actions Career Integration grant [303772]; Swiss National Science Foundation [31003A_130342]; NCCR "Frontiers in Genetics"; University of Geneva; US National Institutes of Health National Center for Biotechnology Information; Harvard Medical School Eleanor and Miles Shore Fellowship; Lundbeck Foundation [R170-2014-1039]; NIJ [2014-DN-BX-K089]; Mary Beryl Patch Turnbull Scholar Program; NSF Graduate Research Fellowship [DGE-1147470]; Simons Foundation SFARI [SF51]; Sloan Foundation; [U54HG3067]; [U54HG3273]; [U01HG5211]; [U54HG3079]; [R01HG2898]; [R01HG2385]; [RC2HG5552]; [U01HG6513]; [U01HG5214]; [U01HG5715]; [U01HG5718]; [U01HG5728]; [U41HG7635]; [U41HG7497]; [R01HG4960]; [R01HG5701]; [R01HG5214]; [R01HG6855]; [R01HG7068]; [R01HG7644]; [DP2OD6514]; [DP5OD9154]; [R01CA166661]; [R01CA172652]; [P01GM99568]; [R01GM59290]; [R01GM104390]; [T32GM7790]; [R01HL87699]; [R01HL104608]; [T32HL94284]; [HHSN268201100040C]; [HHSN272201000025C] FX We thank the many people who were generous with contributing their samples to the project: the African Caribbean in Barbados; Bengali in Bangladesh; British in England and Scotland; Chinese Dai in Xishuangbanna, China; Colombians in Medellin, Colombia; Esan in Nigeria; Finnish in Finland; Gambian in Western Division - Mandinka; Gujarati Indians in Houston, Texas, USA; Han Chinese in Beijing, China; Iberian populations in Spain; Indian Telugu in the UK; Japanese in Tokyo, Japan; Kinh in Ho Chi Minh City, Vietnam; Luhya in Webuye, Kenya; Mende in Sierra Leone; people with African ancestry in the southwest USA; people with Mexican ancestry in Los Angeles, California, USA; Peruvians in Lima, Peru; Puerto Ricans in Puerto Rico; Punjabi in Lahore, Pakistan; southern Han Chinese; Sri Lankan Tamil in the UK; Toscani in Italia; Utah residents (CEPH) with northern and western European ancestry; and Yoruba in Ibadan, Nigeria. Many thanks to the people who contributed to this project: P. Maul, T. Maul, and C. Foster; Z. Chong, X. Fan, W. Zhou, and T. Chen; N. Sengamalay, S. Ott, L. Sadzewicz, J. Liu, and L. Tallon; L. Merson; O. Folarin, D. Asogun, O. Ikpwonmosa, E. Philomena, G. Akpede, S. Okhobgenin, and O. Omoniwa; the staff of the Institute of Lassa Fever Research and Control (ILFRC), Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria; A. Schlattl and T. Zichner; S. Lewis, E. Appelbaum, and L. Fulton; A. Yurovsky and I. Padioleau; N. Kaelin and F. Laplace; E. Drury and H. Arbery; A. Naranjo, M. Victoria Parra, and C. Duque; S. Dokel, B. Lenz, and S. Schrinner; S. Bumpstead; and C. Fletcher-Hoppe. Funding for this work was from the Wellcome Trust Core Award 090532/Z/09/Z and Senior Investigator Award 095552/Z/11/Z (P. D.), and grants WT098051 (R.D.), WT095908 and WT109497 (P. F.), WT086084/Z/08/Z and WT100956/Z/13/Z (G. M.), WT097307 (W.K.), WT0855322/Z/08/Z (R.L.), WT090770/Z/09/Z (D.K.), the Wellcome Trust Major Overseas program in Vietnam grant 089276/Z.09/Z (S. D.), the Medical Research Council UK grant G0801823 (J. L. M.), the UK Biotechnology and Biological Sciences Research Council grants BB/I02593X/1 (G. M.) and BB/I021213/1 (A.R.L.), the British Heart Foundation (C. A. A.), the Monument Trust (J. H.), the European Molecular Biology Laboratory (P. F.), the European Research Council grant 617306 (J. L. M.), the Chinese 863 Program 2012AA02A201, the National Basic Research program of China 973 program no. 2011CB809201, 2011CB809202 and 2011CB809203, Natural Science Foundation of China 31161130357, the Shenzhen Municipal Government of China grant ZYC201105170397A (J. W.), the Canadian Institutes of Health Research Operating grant 136855 and Canada Research Chair (S. G.), Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research (M.K.D.), a Le Fonds de Recherche du Quebec-Sante (FRQS) research fellowship (A. H.), Genome Quebec (P. A.), the Ontario Ministry of Research and Innovation - Ontario Institute for Cancer Research Investigator Award (P. A., J. S.), the Quebec Ministry of Economic Development, Innovation, and Exports grant PSR-SIIRI-195 (P. A.), the German Federal Ministry of Education and Research (BMBF) grants 0315428A and 01GS08201 (R.H.), the Max Planck Society (H. L., G. M., R.S.), BMBF-EPITREAT grant 0316190A (R.H., M. L.), the German Research Foundation (Deutsche Forschungsgemeinschaft) Emmy Noether Grant KO4037/1-1 (J.O.K.), the Beatriu de Pinos Program grants 2006 BP-A 10144 and 2009 BP-B 00274 (M.V.; ), the Spanish National Institute for Health Research grant PRB2 IPT13/0001-ISCIII-SGEFI/FEDER (A. O.), Ewha Womans University (C. L.), the Japan Society for the Promotion of Science Fellowship number PE13075 (N. P.), the Louis Jeantet Foundation (E. T. D.), the Marie Curie Actions Career Integration grant 303772 (C. A.), the Swiss National Science Foundation 31003A_130342 and NCCR "Frontiers in Genetics" (E. T. D.), the University of Geneva (E. T. D., T. L., G. M.), the US National Institutes of Health National Center for Biotechnology Information (S. S.) and grants U54HG3067 (E. S. L.), U54HG3273 and U01HG5211 (R.A.G.), U54HG3079 (R.K.W., E.R.M.), R01HG2898 (S. E. D.), R01HG2385 (E. E. E.), RC2HG5552 and U01HG6513 (G. T. M., G.R.A.), U01HG5214 (A. C.), U01HG5715 (C. D. B.), U01HG5718 (M. G.), U01HG5728 (Y.X.F.), U41HG7635 (R.K.W., E. E. E., P. H. S.), U41HG7497 (C. L., M. A. B., K.C., L. D., E. E. E., M. G., J.O.K., G. T. M., S. A. M., R.E.M., J. L. S., K.Y.), R01HG4960 and R01HG5701 (B. L. B.), R01HG5214 (G. A.), R01HG6855 (S. M.), R01HG7068 (R.E.M.), R01HG7644 (R.D.H.), DP2OD6514(P. S.), DP5OD9154 (J.K.), R01CA166661 (S. E. D.), R01CA172652 (K.C.), P01GM99568 (S.R.B.), R01GM59290 (L. B. J., M. A. B.), R01GM104390 (L. B. J., M.Y.Y.), T32GM7790 (C. D. B., A.R.M.), P01GM99568 (S.R.B.), R01HL87699 and R01HL104608 (K.C.B.), T32HL94284 (J.L.R.F.), and contracts HHSN268201100040C (A.M.R.) and HHSN272201000025C (P. S.), Harvard Medical School Eleanor and Miles Shore Fellowship (K.L.), Lundbeck Foundation Grant R170-2014-1039 (K.L.), NIJ Grant 2014-DN-BX-K089 (Y.E.), the Mary Beryl Patch Turnbull Scholar Program (K.C. B.), NSF Graduate Research Fellowship DGE-1147470 (G. D. P.), the Simons Foundation SFARI award SF51 (M. W.), and a Sloan Foundation Fellowship (R.D. H.). E. E. E. is an investigator of the Howard Hughes Medical Institute. NR 37 TC 229 Z9 231 U1 57 U2 156 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 OCT 1 PY 2015 VL 526 IS 7571 BP 68 EP + DI 10.1038/nature15393 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS5CY UT WOS:000362095100036 ER PT J AU Walter, K Min, JL Huang, J Crooks, L Memari, Y McCarthy, S Perry, JRB Xu, C Futema, M Lawson, D Iotchkova, V Schiffels, S Hendricks, AE Danecek, P Li, R Floyd, J Wain, LV Barroso, I Humphries, SE Hurles, ME Zeggini, E Barrett, JC Plagnol, V Richards, JB Greenwood, CMT Timpson, NJ Durbin, R Soranzo, N Bala, S Clapham, P Coates, G Cox, T Daly, A Danecek, P Du, Y Durbin, R Edkins, S Ellis, P Flicek, P Guo, X Guo, X Huang, L Jackson, DK Joyce, C Keane, T Kolb-Kokocinski, A Langford, C Li, Y Liang, J Lin, H Liu, R Maslen, J McCarthy, S Muddyman, D Quail, MA Stalker, J Sun, J Tian, J Wang, G Wang, J Wang, Y Wong, K Zhang, P Barroso, I Birney, E Boustred, C Chen, L Clement, G Cocca, M Danecek, P Smith, GD Day, INM Day-Williams, A Down, T Dunham, I Durbin, R Evans, DM Gaunt, TR Geihs, M Greenwood, CMT Hart, D Hendricks, AE Howie, B Huang, J Hubbard, T Hysi, P Iotchkova, V Jamshidi, Y Karczewski, KJ Kemp, JP Lachance, G Lawson, D Lek, M Lopes, M MacArthur, DG Marchini, J Mangino, M Mathieson, I McCarthy, S Memari, Y Metrustry, S Min, JL Moayyeri, A Muddyman, D Northstone, K Panoutsopoulou, K Paternoster, L Perry, JRB Quaye, L Richards, JB Ring, S Ritchie, GRS Schiffels, S Shihab, HA Shin, SY Small, KS Artigas, MS Soranzo, N Southam, L Spector, TD St Pourcain, B Surdulescu, G Tachmazidou, I Timpson, NJ Tobin, MD Valdes, AM Visscher, PM Wain, LV Walter, K Ward, K Wilson, SG Wong, K Yang, J Zeggini, E Zhang, F Zheng, HF Anney, R Ayub, M Barrett, JC Blackwood, D Bolton, PF Breen, G Collier, DA Craddock, N Crooks, L Curran, S Curtis, D Durbin, R Gallagher, L Geschwind, D Gurling, H Holmans, P Lee, I Lonnqvist, J McCarthy, S McGuffin, P McIntosh, AM McKechanie, AG McQuillin, A Morris, J Muddyman, D O'Donovan, MC Owen, MJ Palotie, A Parr, JR Paunio, T Pietilainen, O Rehnstrom, K Sharp, SI Skuse, D St Clair, D Suvisaari, J Walters, JTR Williams, HJ Barroso, I Bochukova, E Bounds, R Dominiczak, A Durbin, R Farooqi, IS Hendricks, AE Keogh, J Marenne, GL McCarthy, S Morris, A Muddyman, D O'Rahilly, S Porteous, DJ Smith, BH Tachmazidou, I Wheeler, E Zeggini, E Al Turki, S Anderson, CA Antony, D Barroso, IS Beales, P Bentham, J Bhattacharya, S Calissano, M Carss, K Chatterjee, K Cirak, S Cosgrove, C Durbin, R Fitzpatrick, DR Floyd, J Foley, AR Franklin, CS Futema, M Grozeva, D Humphries, SE Hurles, ME McCarthy, S Mitchison, HM Muddyman, D Muntoni, F O'Rahilly, S Onoufriadis, A Parker, V Payne, F Plagnol, V Raymond, FL Roberts, N Savage, DB Scambler, P Schmidts, M Schoenmakers, N Semple, RK Serra, E Spasic-Boskovic, O Stevens, E van Kogelenberg, M Vijayarangakannan, P Walter, K Williamson, KA Wilson, C Whyte, T Ciampi, A Greenwood, CMT Hendricks, AE Li, R Metrustry, S Oualkacha, K Tachmazidou, I Xu, CJ Zeggini, E Bobrow, M Bolton, PF Durbin, R Fitzpatrick, DR Griffin, H Hurles, ME Kaye, J Kennedy, K Kent, A Muddyman, D Muntoni, F Raymond, FL Semple, RK Smee, C Spector, TD Timpson, NJ Charlton, R Ekong, R Futema, M Humphries, SE Khawaja, F Lopes, LR Migone, N Payne, SJ Plagnol, V Pollitt, RC Povey, S Ridout, CK Robinson, RL Scott, RH Shaw, A Syrris, P Taylor, R Vandersteen, AM Barrett, JC Barroso, I Smith, GD Durbin, R Farooqi, IS Fitzpatrick, DR Hurles, ME Kaye, J Kennedy, K Langford, C McCarthy, S Muddyman, D Owen, MJ Palotie, A Richards, JB Soranzo, N Spector, TD Stalker, J Timpson, NJ Zeggini, E Amuzu, A Casas, JP Chambers, JC Cocca, M Dedoussis, G Gambaro, G Gasparini, P Gaunt, TR Huang, J Iotchkova, V Isaacs, A Johnson, J Kleber, ME Kooner, JS Langenberg, C Luan, J Malerba, G Marz, W Matchan, A Min, JL Morris, R Nordestgaard, BG Benn, M Ring, S Scott, RA Soranzo, N Southam, L Timpson, NJ Toniolo, D Traglia, M Tybjaerg-Hansen, A van Duijn, CM van Leeuwen, EM Varbo, A Whincup, P Zaza, G Zeggini, E Zhang, WH AF Walter, Klaudia Min, Josine L. Huang, Jie Crooks, Lucy Memari, Yasin McCarthy, Shane Perry, John R. B. Xu, ChangJiang Futema, Marta Lawson, Daniel Iotchkova, Valentina Schiffels, Stephan Hendricks, Audrey E. Danecek, Petr Li, Rui Floyd, James Wain, Louise V. Barroso, Ines Humphries, Steve E. Hurles, Matthew E. Zeggini, Eleftheria Barrett, Jeffrey C. Plagnol, Vincent Richards, J. Brent Greenwood, Celia M. T. Timpson, Nicholas J. Durbin, Richard Soranzo, Nicole Bala, Senduran Clapham, Peter Coates, Guy Cox, Tony Daly, Allan Danecek, Petr Du, Yuanping Durbin, Richard Edkins, Sarah Ellis, Peter Flicek, Paul Guo, Xiaosen Guo, Xueqin Huang, Liren Jackson, David K. Joyce, Chris Keane, Thomas Kolb-Kokocinski, Anja Langford, Cordelia Li, Yingrui Liang, Jieqin Lin, Hong Liu, Ryan Maslen, John McCarthy, Shane Muddyman, Dawn Quail, Michael A. Stalker, Jim Sun, Jianping Tian, Jing Wang, Guangbiao Wang, Jun Wang, Yu Wong, Kim Zhang, Pingbo Barroso, Ines Birney, Ewan Boustred, Chris Chen, Lu Clement, Gail Cocca, Massimiliano Danecek, Petr Smith, George Davey Day, Ian N. M. Day-Williams, Aaron Down, Thomas Dunham, Ian Durbin, Richard Evans, David M. Gaunt, Tom R. Geihs, Matthias Greenwood, Celia M. T. Hart, Deborah Hendricks, Audrey E. Howie, Bryan Huang, Jie Hubbard, Tim Hysi, Pirro Iotchkova, Valentina Jamshidi, Yalda Karczewski, Konrad J. Kemp, John P. Lachance, Genevieve Lawson, Daniel Lek, Monkol Lopes, Margarida MacArthur, Daniel G. Marchini, Jonathan Mangino, Massimo Mathieson, Iain McCarthy, Shane Memari, Yasin Metrustry, Sarah Min, Josine L. Moayyeri, Alireza Muddyman, Dawn Northstone, Kate Panoutsopoulou, Kalliope Paternoster, Lavinia Perry, John R. B. Quaye, Lydia Richards, J. Brent Ring, Susan Ritchie, Graham R. S. Schiffels, Stephan Shihab, Hashem A. Shin, So-Youn Small, Kerrin S. Artigas, Maria Soler Soranzo, Nicole Southam, Lorraine Spector, Timothy D. St Pourcain, Beate Surdulescu, Gabriela Tachmazidou, Ioanna Timpson, Nicholas J. Tobin, Martin D. Valdes, Ana M. Visscher, Peter M. Wain, Louise V. Walter, Klaudia Ward, Kirsten Wilson, Scott G. Wong, Kim Yang, Jian Zeggini, Eleftheria Zhang, Feng Zheng, Hou-Feng Anney, Richard Ayub, Muhammad Barrett, Jeffrey C. Blackwood, Douglas Bolton, Patrick F. Breen, Gerome Collier, David A. Craddock, Nick Crooks, Lucy Curran, Sarah Curtis, David Durbin, Richard Gallagher, Louise Geschwind, Daniel Gurling, Hugh Holmans, Peter Lee, Irene Lonnqvist, Jouko McCarthy, Shane McGuffin, Peter McIntosh, Andrew M. McKechanie, Andrew G. McQuillin, Andrew Morris, James Muddyman, Dawn O'Donovan, Michael C. Owen, Michael J. Palotie, Aarno Parr, Jeremy R. Paunio, Tiina Pietilainen, Olli Rehnstrom, Karola Sharp, Sally I. Skuse, David St Clair, David Suvisaari, Jaana Walters, James T. R. Williams, Hywel J. Barroso, Ines Bochukova, Elena Bounds, Rebecca Dominiczak, Anna Durbin, Richard Farooqi, I. Sadaf Hendricks, Audrey E. Keogh, Julia Marenne, Gae Lle McCarthy, Shane Morris, Andrew Muddyman, Dawn O'Rahilly, Stephen Porteous, David J. Smith, Blair H. Tachmazidou, Ioanna Wheeler, Eleanor Zeggini, Eleftheria Al Turki, Saeed Anderson, Carl A. Antony, Dinu Barroso, Ines Beales, Phil Bentham, Jamie Bhattacharya, Shoumo Calissano, Mattia Carss, Keren Chatterjee, Krishna Cirak, Sebahattin Cosgrove, Catherine Durbin, Richard Fitzpatrick, David R. Floyd, James Foley, A. Reghan Franklin, Christopher S. Futema, Marta Grozeva, Detelina Humphries, Steve E. Hurles, Matthew E. McCarthy, Shane Mitchison, Hannah M. Muddyman, Dawn Muntoni, Francesco O'Rahilly, Stephen Onoufriadis, Alexandros Parker, Victoria Payne, Felicity Plagnol, Vincent Raymond, F. Lucy Roberts, Nicola Savage, David B. Scambler, Peter Schmidts, Miriam Schoenmakers, Nadia Semple, Robert K. Serra, Eva Spasic-Boskovic, Olivera Stevens, Elizabeth van Kogelenberg, Margriet Vijayarangakannan, Parthiban Walter, Klaudia Williamson, Kathleen A. Wilson, Crispian Whyte, Tamieka Ciampi, Antonio Greenwood, Celia M. T. Hendricks, Audrey E. Li, Rui Metrustry, Sarah Oualkacha, Karim Tachmazidou, Ioanna Xu, ChangJiang Zeggini, Eleftheria Bobrow, Martin Bolton, Patrick F. Durbin, Richard Fitzpatrick, David R. Griffin, Heather Hurles, Matthew E. Kaye, Jane Kennedy, Karen Kent, Alastair Muddyman, Dawn Muntoni, Francesco Raymond, F. Lucy Semple, Robert K. Smee, Carol Spector, Timothy D. Timpson, Nicholas J. Charlton, Ruth Ekong, Rosemary Futema, Marta Humphries, Steve E. Khawaja, Farrah Lopes, Luis R. Migone, Nicola Payne, Stewart J. Plagnol, Vincent Pollitt, Rebecca C. Povey, Sue Ridout, Cheryl K. Robinson, Rachel L. Scott, Richard H. Shaw, Adam Syrris, Petros Taylor, Rohan Vandersteen, Anthony M. Barrett, Jeffrey C. Barroso, Ines Smith, George Davey Durbin, Richard Farooqi, I. Sadaf Fitzpatrick, David R. Hurles, Matthew E. Kaye, Jane Kennedy, Karen Langford, Cordelia McCarthy, Shane Muddyman, Dawn Owen, Michael J. Palotie, Aarno Richards, J. Brent Soranzo, Nicole Spector, Timothy D. Stalker, Jim Timpson, Nicholas J. Zeggini, Eleftheria Amuzu, Antoinette Casas, Juan Pablo Chambers, John C. Cocca, Massimiliano Dedoussis, George Gambaro, Giovanni Gasparini, Paolo Gaunt, Tom R. Huang, Jie Iotchkova, Valentina Isaacs, Aaron Johnson, Jon Kleber, Marcus E. Kooner, Jaspal S. Langenberg, Claudia Luan, Jian'an Malerba, Giovanni Maerz, Winfried Matchan, Angela Min, Josine L. Morris, Richard Nordestgaard, Borge G. Benn, Marianne Ring, Susan Scott, Robert A. Soranzo, Nicole Southam, Lorraine Timpson, Nicholas J. Toniolo, Daniela Traglia, Michela Tybjaerg-Hansen, Anne van Duijn, Cornelia M. van Leeuwen, Elisabeth M. Varbo, Anette Whincup, Peter Zaza, Gianluigi Zeggini, Eleftheria Zhang, Weihua CA UK10K Consortium UCLEB Consortium TI The UK10K project identifies rare variants in health and disease SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; OF-FUNCTION MUTATIONS; LOW-FREQUENCY; INCIDENTAL FINDINGS; SEQUENCE VARIATION; COMPLEX TRAITS; POPULATION; COMMON; HERITABILITY; APOC3 AB The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7x) or exomes (high read depth, 80x) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results. C1 [Walter, Klaudia; Huang, Jie; Crooks, Lucy; Memari, Yasin; McCarthy, Shane; Iotchkova, Valentina; Hendricks, Audrey E.; Danecek, Petr; Floyd, James; Barroso, Ines; Hurles, Matthew E.; Zeggini, Eleftheria; Barrett, Jeffrey C.; Durbin, Richard; Soranzo, Nicole; Bala, Senduran; Coates, Guy; Cox, Tony; Daly, Allan; Edkins, Sarah; Ellis, Peter; Flicek, Paul; Jackson, David K.; Joyce, Chris; Keane, Thomas; Kolb-Kokocinski, Anja; Langford, Cordelia; Maslen, John; Muddyman, Dawn; Quail, Michael A.; Stalker, Jim; Wong, Kim; Chen, Lu; Day-Williams, Aaron; Down, Thomas; Geihs, Matthias; Hubbard, Tim; Lopes, Margarida; Panoutsopoulou, Kalliope; Ritchie, Graham R. S.; Southam, Lorraine; Tachmazidou, Ioanna; Morris, James; Palotie, Aarno; Pietilainen, Olli; Rehnstrom, Karola; Marenne, Gae Lle; Wheeler, Eleanor; Anderson, Carl A.; Carss, Keren; Foley, A. Reghan; Franklin, Christopher S.; Payne, Felicity; Serra, Eva; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Smee, Carol; Barrett, Jeffrey C.; Barroso, Ines; Matchan, Angela] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. [Soranzo, Nicole; Chen, Lu] Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England. [Min, Josine L.; Timpson, Nicholas J.; Smith, George Davey; Evans, David M.; Gaunt, Tom R.; Northstone, Kate; Paternoster, Lavinia; Shihab, Hashem A.; Shin, So-Youn; St Pourcain, Beate] Univ Bristol, Sch Social & Community Med, MRC, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England. [Crooks, Lucy] Sheffield Childrens NHS Fdn Trust, Sheffield Diagnost Genet Serv, Sheffield S10 2TH, S Yorkshire, England. [Perry, John R. B.; Richards, J. Brent; Clement, Gail; Hart, Deborah; Hysi, Pirro; Lachance, Genevieve; Mangino, Massimo; Metrustry, Sarah; Moayyeri, Alireza; Quaye, Lydia; Small, Kerrin S.; Spector, Timothy D.; Surdulescu, Gabriela; Valdes, Ana M.; Ward, Kirsten; Wilson, Scott G.; Zhang, Feng] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England. [Perry, John R. B.] Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC,Epidemiol Unit, Cambridge CB2 0QQ, England. [Xu, ChangJiang; Li, Rui; Greenwood, Celia M. T.; Sun, Jianping; Richards, J. Brent; Zheng, Hou-Feng; Foley, A. Reghan] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. [Xu, ChangJiang; Greenwood, Celia M. T.; Sun, Jianping; Richards, J. Brent; Ciampi, Antonio] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada. [Futema, Marta; Humphries, Steve E.] UCL, BHF Labs, Cardiovasc Genet, Inst Cardiovasc Sci, London WC1E 6JJ, England. [Lawson, Daniel] Univ Bristol, Sch Math, Bristol BS8 2BN, Avon, England. [Lawson, Daniel] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England. [Iotchkova, Valentina; Flicek, Paul; Birney, Ewan; Dunham, Ian; Ritchie, Graham R. S.] European Mol Biol Lab, European Bioinformat Inst, Cambridge CB10 1SD, England. Univ Colorado, Dept Math & Stat Sci, Denver, CO 80204 USA. [Li, Rui; Richards, J. Brent; Zheng, Hou-Feng] McGill Univ, Jewish Gen Hosp, Dept Med, Montreal, PQ H3A 1B1, Canada. [Richards, J. Brent; Morris, Richard] McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada. [Floyd, James] Univ London, John Vane Sci Ctr, Genome Ctr, London EC1M 6BQ, England. [Wain, Louise V.; Artigas, Maria Soler; Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England. [Artigas, Maria Soler; Tobin, Martin D.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. [Barroso, Ines; Bochukova, Elena; Bounds, Rebecca; Farooqi, I. 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[Ridout, Cheryl K.] Guys Hosp, Viapath, Mol Genet, London SE1 9RT, England. [Scott, Richard H.] Great Ormond St Hosp Sick Children, Dept Clin Genet, London WC1N 3JH, England. [Shaw, Adam] Guys & St Thomas NHS Fdn Trust, Clin Genet, London SE1 9RT, England. [Vandersteen, Anthony M.] Maritime Med Genet Serv, Halifax, NS B3K 6R8, Canada. [Amuzu, Antoinette; Casas, Juan Pablo] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. [Chambers, John C.; Zhang, Weihua] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1PG, England. [Dedoussis, George] Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens 17671, Greece. [Gambaro, Giovanni] Univ Cattolica Sacro Cuore, Columbus Gemelli Univ Hosp, Inst Internal Med, Div Nephrol & Dialysis,Renal Program, I-00168 Rome, Italy. [Gasparini, Paolo] Sidra, Expt Genet Div, Doha, Qatar. [Isaacs, Aaron; van Duijn, Cornelia M.; van Leeuwen, Elisabeth M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands. [Johnson, Jon] UCL, UCL Inst Educ, Dept Quantitat Social Sci, London WC1H 0AL, England. [Kleber, Marcus E.] Fac Med, Dept Med 5, D-68167 Mannheim, Germany. [Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London W12 0NN, England. [Langenberg, Claudia; Luan, Jian'an; Scott, Robert A.] Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England. [Malerba, Giovanni] Univ Verona, Dept Life & Reprod Sci, Biol & Genet, I-37134 Verona, Italy. [Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8036 Graz, Austria. [Maerz, Winfried] Synlab Serv GmbH, Synlab Acad, D-68161 Mannheim, Germany. [Maerz, Winfried] Heidelberg Univ, Mannheim Med Fac, Med Clin Nephrol 5, Hypertensiol,Rheumatol,Endocrinolgy,Diabetol, D-68167 Mannheim, Germany. [Morris, Richard] Sch Social & Community Med, Bristol BS8 2PS, Avon, England. [Nordestgaard, Borge G.; Benn, Marianne; Varbo, Anette] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark. [Nordestgaard, Borge G.; Benn, Marianne; Varbo, Anette] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, DK-2730 Herlev, Denmark. [Nordestgaard, Borge G.; Benn, Marianne; Tybjaerg-Hansen, Anne; Varbo, Anette] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark. [Toniolo, Daniela; Traglia, Michela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy. [Tybjaerg-Hansen, Anne] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem KB3011, DK-2100 Copenhagen, Denmark. [Whincup, Peter] St Georges Univ London, Populat Hlth Res Inst, London SW17 0RE, England. [Zaza, Gianluigi] Univ Verona, Dept Med, Renal Unit, I-37126 Verona, Italy. RP Soranzo, N (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1HH, England. EM rd@sanger.ac.uk; ns6@sanger.ac.uk RI Wang, Jun/B-9503-2016; Bolton, Patrick/E-8501-2010; Yang, Jian/A-5852-2010; mangino, massimo/F-5134-2011; McQuillin, Andrew/C-1623-2008; Davey Smith, George/A-7407-2013; Wang, Jun/C-8434-2016; Soler Artigas, Maria/L-6529-2013; Gaunt, Tom/O-3918-2014; Hendricks, Audrey/I-4127-2016; OI McIntosh, Andrew/0000-0002-0198-4588; Wain, Louise/0000-0003-4951-1867; Visscher, Peter/0000-0002-2143-8760; Zaza, Gianluigi/0000-0002-6004-6196; Kemp, John/0000-0002-9105-2249; Evans, David/0000-0003-0663-4621; FitzPatrick, David R./0000-0003-4861-969X; Lawson, Daniel/0000-0002-5311-6213; Timpson, Nicholas/0000-0002-7141-9189; Payne, Felicity/0000-0003-4228-581X; Bochukova, Elena/0000-0003-0275-1548; Memari, Yasin/0000-0002-1747-542X; Moayyeri, Alireza/0000-0002-9143-2161; Johnson, Jon/0000-0001-8482-1620; Malerba, Giovanni/0000-0001-8705-8560; Gallagher, Louise/0000-0001-9462-2836; Cocca, Massimiliano/0000-0002-1127-7596; Hubbard, Tim @timjph/0000-0002-1767-9318; Wang, Jun/0000-0002-2113-5874; Whincup, Peter/0000-0002-5589-4107; Plagnol, Vincent/0000-0002-5597-9215; Humphries, Stephen E/0000-0002-8221-6547; Paternoster, Lavinia/0000-0003-2514-0889; Flicek, Paul/0000-0002-3897-7955; Dunham, Ian/0000-0003-2525-5598; Birney, Ewan/0000-0001-8314-8497; Schiffels, Stephan/0000-0002-1017-9150; Lopes, Luis/0000-0002-6408-4667; Farooqi, Sadaf/0000-0001-7609-3504; Schmidts, Miriam/0000-0002-1714-6749; McCarthy, Shane/0000-0002-2715-4187; Small, Kerrin/0000-0003-4566-0005; Bolton, Patrick/0000-0002-5270-6262; Yang, Jian/0000-0003-2001-2474; mangino, massimo/0000-0002-2167-7470; McQuillin, Andrew/0000-0003-1567-2240; Davey Smith, George/0000-0002-1407-8314; Anney, Richard/0000-0002-6083-407X; McKechanie, Andrew/0000-0003-4273-9906; Pollitt, Rebecca/0000-0002-8864-397X; Wang, Jun/0000-0002-8540-8931; Soler Artigas, Maria/0000-0002-3213-1107; Gaunt, Tom/0000-0003-0924-3247; Hendricks, Audrey/0000-0002-7152-0287; Karczewski, Konrad/0000-0003-2878-4671; Zeggini, Eleftheria/0000-0003-4238-659X; Coates, Guy/0000-0002-8055-4796; Walters, James/0000-0002-6980-4053; Iotchkova, Valentina/0000-0001-5057-0210; Soranzo, Nicole/0000-0003-1095-3852; Suvisaari, Jaana/0000-0001-7167-0990; Semple, Robert/0000-0001-6539-3069; Barrett, Jeffrey/0000-0002-1152-370X FU Wellcome Trust [WT091310] FX This study makes use of data generated by the UK10K Consortium. The Wellcome Trust provided funding for UK10K (WT091310). Additional grant support and acknowledgements can be found in the Supplementary Information. NR 49 TC 91 Z9 92 U1 8 U2 50 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 OCT 1 PY 2015 VL 526 IS 7571 BP 82 EP + DI 10.1038/nature14962 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS5CY UT WOS:000362095100038 ER PT J AU Zheng, HF Forgetta, V Hsu, YH Estrada, K Rosello-Diez, A Leo, PJ Dahia, CL Park-Min, KH Tobias, JH Kooperberg, C Kleinman, A Styrkarsdottir, U Liu, CT Uggla, C Evans, DS Nielson, CM Walter, K Pettersson-Kymmer, U McCarthy, S Eriksson, J Kwan, T Jhamai, M Trajanoska, K Memari, Y Min, J Huang, J Danecek, P Wilmot, B Li, R Chou, WC Mokry, LE Moayyeri, A Claussnitzer, M Cheng, CH Cheung, W Medina-Gomez, C Ge, B Chen, SH Choi, K Oei, L Fraser, J Kraaij, R Hibbs, MA Gregson, CL Paquette, D Hofman, A Wibom, C Tranah, GJ Marshall, M Gardiner, BB Cremin, K Auer, P Hsu, L Ring, S Tung, JY Thorleifsson, G Enneman, AW van Schoor, NM de Groot, LCPGM van der Velde, N Melin, B Kemp, JP Christiansen, C Sayers, A Zhou, YH Calderari, S van Rooij, J Carlson, C Peters, U Berlivet, S Dostie, J Uitterlinden, AG Williams, SR Farber, C Grinberg, D LaCroix, AZ Haessler, J Chasman, DI Giulianini, F Rose, LM Ridker, PM Eisman, JA Nguyen, TV Center, JR Nogues, X Garcia-Giralt, N Launer, LL Gudnason, V Mellstrom, D Vandenput, L Amin, N van Duijn, CM Karlsson, MK Ljunggren, O Svensson, O Hallmans, G Rousseau, F Giroux, S Bussiere, J Arp, PP Koromani, F Prince, RL Lewis, JR Langdahl, BL Hermann, AP Jensen, JEB Kaptoge, S Khaw, KT Reeve, J Formosa, MM Xuereb-Anastasi, A Akesson, K McGuigan, FE Garg, G Olmos, JM Zarrabeitia, MT Riancho, JA Ralston, SH Alonso, N Jiang, X Goltzman, D Pastinen, T Grundberg, E Gauguier, D Orwoll, ES Karasik, D Davey-Smith, G Smith, AV Siggeirsdottir, K Harris, TB Zillikens, MC van Meurs, JBJ Thorsteinsdottir, U Maurano, MT Timpson, NJ Soranzo, N Durbin, R Wilson, S Ntzani, EE Brown, MA Stefansson, K Hinds, DA Spector, T Cupples, LA Ohlsson, C Greenwood, CMT Jackson, RD Rowe, DW Loomis, CA Evans, DM Ackert-Bicknell, CL Joyner, AL Duncan, EL Kiel, DP Rivadeneira, F Richards, JB AF Zheng, Hou-Feng Forgetta, Vincenzo Hsu, Yi-Hsiang Estrada, Karol Rosello-Diez, Alberto Leo, Paul J. Dahia, Chitra L. Park-Min, Kyung Hyun Tobias, Jonathan H. Kooperberg, Charles Kleinman, Aaron Styrkarsdottir, Unnur Liu, Ching-Ti Uggla, Charlotta Evans, Daniel S. Nielson, Carrie M. Walter, Klaudia Pettersson-Kymmer, Ulrika McCarthy, Shane Eriksson, Joel Kwan, Tony Jhamai, Mila Trajanoska, Katerina Memari, Yasin Min, Josine Huang, Jie Danecek, Petr Wilmot, Beth Li, Rui Chou, Wen-Chi Mokry, Lauren E. Moayyeri, Alireza Claussnitzer, Melina Cheng, Chia-Ho Cheung, Warren Medina-Gomez, Carolina Ge, Bing Chen, Shu-Huang Choi, Kwangbom Oei, Ling Fraser, James Kraaij, Robert Hibbs, Matthew A. Gregson, Celia L. Paquette, Denis Hofman, Albert Wibom, Carl Tranah, Gregory J. Marshall, Mhairi Gardiner, Brooke B. Cremin, Katie Auer, Paul Hsu, Li Ring, Sue Tung, Joyce Y. Thorleifsson, Gudmar Enneman, Anke W. van Schoor, Natasja M. de Groot, Lisette C. P. G. M. van der Velde, Nathalie Melin, Beatrice Kemp, John P. Christiansen, Claus Sayers, Adrian Zhou, Yanhua Calderari, Sophie van Rooij, Jeroen Carlson, Chris Peters, Ulrike Berlivet, Soizik Dostie, Josee Uitterlinden, Andre G. Williams, Stephen R. Farber, Charles Grinberg, Daniel LaCroix, Andrea Z. Haessler, Jeff Chasman, Daniel I. Giulianini, Franco Rose, Lynda M. Ridker, Paul M. Eisman, John A. Nguyen, Tuan V. Center, Jacqueline R. Nogues, Xavier Garcia-Giralt, Natalia Launer, Lenore L. Gudnason, Vilmunder Mellstrom, Dan Vandenput, Liesbeth Amin, Najaf van Duijn, Cornelia M. Karlsson, Magnus K. Ljunggren, Osten Svensson, Olle Hallmans, Goran Rousseau, Francois Giroux, Sylvie Bussiere, Johanne Arp, Pascal P. Koromani, Fjorda Prince, Richard L. Lewis, Joshua R. Langdahl, Bente L. Hermann, A. Pernille Jensen, Jens-Erik B. Kaptoge, Stephen Khaw, Kay-Tee Reeve, Jonathan Formosa, Melissa M. Xuereb-Anastasi, Angela Akesson, Kristina McGuigan, Fiona E. Garg, Gaurav Olmos, Jose M. Zarrabeitia, Maria T. Riancho, Jose A. Ralston, Stuart H. Alonso, Nerea Jiang, Xi Goltzman, David Pastinen, Tomi Grundberg, Elin Gauguier, Dominique Orwoll, Eric S. Karasik, David Davey-Smith, George Smith, Albert V. Siggeirsdottir, Kristin Harris, Tamara B. Zillikens, M. Carola van Meurs, Joyce B. J. Thorsteinsdottir, Unnur Maurano, Matthew T. Timpson, Nicholas J. Soranzo, Nicole Durbin, Richard Wilson, ScottG. Ntzani, Evangelia E. Brown, Matthew A. Stefansson, Kari Hinds, David A. Spector, Tim Cupples, L. Adrienne Ohlsson, Claes Greenwood, Celia M. T. Jackson, Rebecca D. Rowe, David W. Loomis, Cynthia A. Evans, David M. Ackert-Bicknell, Cheryl L. Joyner, Alexandra L. Duncan, Emma L. Kiel, Douglas P. Rivadeneira, Fernando Richards, J. Brent CA AOGC Consortium UK10K Consortium TI Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture SO NATURE LA English DT Article ID WIDE ASSOCIATION LOCI; MINERAL DENSITY; COMPLEX TRAITS; HUMAN-DISEASES; VARIANTS; MOUSE; ENGRAILED-1; OSTEOPOROSIS; METAANALYSIS; GENE AB The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population. C1 [Zheng, Hou-Feng; Forgetta, Vincenzo; Li, Rui; Richards, J. Brent] McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada. [Zheng, Hou-Feng; Forgetta, Vincenzo; Li, Rui; Richards, J. Brent] McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada. [Zheng, Hou-Feng; Forgetta, Vincenzo; Li, Rui; Richards, J. Brent] McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada. [Zheng, Hou-Feng; Forgetta, Vincenzo; Li, Rui; Richards, J. Brent] McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada. [Zheng, Hou-Feng; Forgetta, Vincenzo; Li, Rui; Mokry, Lauren E.; Greenwood, Celia M. T.; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada. [Hsu, Yi-Hsiang; Chou, Wen-Chi; Claussnitzer, Melina; Cheng, Chia-Ho; Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Hsu, Yi-Hsiang; Estrada, Karol; Chou, Wen-Chi; Claussnitzer, Melina; Chasman, Daniel I.; Ridker, Paul M.; Kiel, Douglas P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Hsu, Yi-Hsiang; Estrada, Karol; Claussnitzer, Melina; Kiel, Douglas P.] Broad Inst MIT & Harvard, Boston, MA 02115 USA. [Estrada, Karol; Jhamai, Mila; Trajanoska, Katerina; Medina-Gomez, Carolina; Oei, Ling; Kraaij, Robert; Enneman, Anke W.; van der Velde, Nathalie; van Rooij, Jeroen; Uitterlinden, Andre G.; Arp, Pascal P.; Koromani, Fjorda; Zillikens, M. Carola; van Meurs, Joyce B. J.; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Rosello-Diez, Alberto; Joyner, Alexandra L.] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA. [Leo, Paul J.; Marshall, Mhairi; Gardiner, Brooke B.; Cremin, Katie; Kemp, John P.; Brown, Matthew A.; Evans, David M.; Duncan, Emma L.] Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Dahia, Chitra L.] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA. 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[Gregson, Celia L.; Sayers, Adrian] Univ Bristol, Musculoskeletal Res Unit, Bristol BS10 5NB, Avon, England. [Wibom, Carl; Melin, Beatrice] Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden. [Auer, Paul] Univ Wisconsin, Sch Publ Hlth, Milwaukee, WI 53726 USA. [Ring, Sue] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England. [Thorleifsson, Gudmar] deCODE Genet, Dept Stat, IS-101 Reykjavik, Iceland. [van Schoor, Natasja M.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands. [van Schoor, Natasja M.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, NL-1007 MB Amsterdam, Netherlands. [de Groot, Lisette C. P. G. M.] Wageningen Univ, Dept Human Nutr, NL-6700 EV Wageningen, Netherlands. [van der Velde, Nathalie] Acad Med Ctr, Sect Geriatr, Dept Internal Med, NL-1105 Amsterdam, Netherlands. [Christiansen, Claus] Nord Biosci, DK-2730 Herlev, Denmark. [Calderari, Sophie; Gauguier, Dominique] INSERM, UMRS 1138, Cordeliers Res Ctr, F-75006 Paris, France. [Calderari, Sophie; Gauguier, Dominique] Univ Paris 06, Inst Cardiometab & Nutr, F-75013 Paris, France. [Williams, Stephen R.; Farber, Charles; Nogues, Xavier] Univ Virginia, Ctr Publ Hlth Genom, Dept Med, Charlottesville, VA 22908 USA. [Williams, Stephen R.; Farber, Charles; Nogues, Xavier] Univ Virginia, Ctr Publ Hlth Genom, Dept Cardiovasc Med, Charlottesville, VA 22908 USA. [Grinberg, Daniel] Univ Barcelona, Dept Genet, E-08028 Barcelona, Spain. [Grinberg, Daniel] Ctr Biomed Network Res Rare Dis CIBERER, U720, Barcelona 28029, Spain. [Grinberg, Daniel] Univ Barcelona, Inst Biomed, Dept Human Mol Genet, E-08028 Barcelona, Spain. [LaCroix, Andrea Z.] Univ Calif San Diego, Womens Hlth Ctr Excellence Family Med & Publ Hlth, San Diego, CA 92103 USA. [Chasman, Daniel I.; Giulianini, Franco; Rose, Lynda M.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Eisman, John A.; Nguyen, Tuan V.; Center, Jacqueline R.] Garvan Inst Med Res, Osteoporosis & Bone Biol Program, Sydney, NSW 2010, Australia. [Eisman, John A.] Univ Notre Dame Australia, Sch Med Sydney, Sydney, NSW 6959, Australia. [Eisman, John A.; Nguyen, Tuan V.; Center, Jacqueline R.] NSW Univ, St Vincents Hosp, Sydney, NSW 2010, Australia. [Eisman, John A.; Nguyen, Tuan V.; Center, Jacqueline R.] NSW Univ, Sch Clin, Sydney, NSW 2010, Australia. [Nogues, Xavier; Garcia-Giralt, Natalia] Inst Hosp Mar Invest Med, Musculoskeletal Res Grp, Barcelona 08003, Spain. [Garcia-Giralt, Natalia] Inst Hlth Carlos III, Cooperat Res Network Aging & Fragil RETICEF, Madrid 28029, Spain. [Nogues, Xavier] Univ Autonoma Barcelona, Hosp Mar, Dept Internal Med, E-08193 Barcelona, Spain. [Launer, Lenore L.] NIA, Neuroepidemiol Sect, NIH, Bethesda, MD 20892 USA. [Gudnason, Vilmunder; Smith, Albert V.; Siggeirsdottir, Kristin] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Gudnason, Vilmunder; Smith, Albert V.; Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Amin, Najaf; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands. [Karlsson, Magnus K.; Akesson, Kristina] Skane Univ Hosp, Dept Orthopaed, S-20502 Malmo, Sweden. [Ljunggren, Osten] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden. [Svensson, Olle] Umea Univ, Dept Surg & Perioperat Sci, S-90185 Umea, Sweden. [Rousseau, Francois] Univ Laval, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ G1V 0A6, Canada. [Rousseau, Francois; Giroux, Sylvie; Bussiere, Johanne] CHU Quebec, Ctr Rech, Axe Sante Populat & Prat Optimales Sante, Quebec City, PQ G1V 4G2, Canada. [Prince, Richard L.; Lewis, Joshua R.; Wilson, ScottG.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia. [Prince, Richard L.; Lewis, Joshua R.] Univ Western Australia, Dept Med, Perth, WA 6009, Australia. [Langdahl, Bente L.] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus C, Denmark. [Hermann, A. Pernille] Odense Univ Hosp, Dept Endocrinol, DK-5000 Odense C, Denmark. [Jensen, Jens-Erik B.] Hvidovre Univ Hosp, Dept Endocrinol, DK-2650 Hvidovre, Denmark. [Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge CB2 2QQ, England. [Reeve, Jonathan] Univ Cambridge, Med & Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Reeve, Jonathan] Univ Oxford, Botnar Res Ctr, Inst Musculoskeletal Sci, Oxford OX3 7LD, England. [Formosa, Melissa M.; Xuereb-Anastasi, Angela] Univ Malta, Dept Appl Biomed Sci, Fac Hlth Sci, MSD-2080 Msida, Malta. [Akesson, Kristina; McGuigan, Fiona E.; Garg, Gaurav] Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, S-20502 Lund, Sweden. [Olmos, Jose M.; Riancho, Jose A.] Univ Cantabria, Dept Med & Psychiat, Santander 39011, Spain. [Olmos, Jose M.; Riancho, Jose A.] Hosp UM Valdecilla IDIVAL, Dept Internal Med, Santander 39008, Spain. [Zarrabeitia, Maria T.] Univ Cantabria, Dept Legal Med, Santander 39011, Spain. [Ralston, Stuart H.; Alonso, Nerea] Univ Edinburgh, Inst Genet & Mol Med, Western Gen Hosp, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Jiang, Xi; Rowe, David W.] Univ Connecticut, Ctr Hlth, Coll Dent Med, Dept Reconstruct Sci, Farmington, CT 06030 USA. [Goltzman, David] McGill Univ, Dept Med & Physiol, Montreal, PQ H4A 3J1, Canada. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Karasik, David] Bar Ilan Univ, Fac Med Galilee, IL-13010 Safed, Israel. [Harris, Tamara B.] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA. [Maurano, Matthew T.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Wilson, ScottG.] Univ Western Australia, Sch Med & Pharmacol, Crawley 6009, Australia. [Ntzani, Evangelia E.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ntzani, Evangelia E.] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02903 USA. [Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland. [Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Greenwood, Celia M. T.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada. [Greenwood, Celia M. T.] McGill Univ, Gerald Bronfman Ctr, Dept Oncol, Montreal, PQ H2W 1S6, Canada. [Jackson, Rebecca D.] Ohio State Univ, Dept Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Loomis, Cynthia A.] NYU, Sch Med, Ronald O Perelman Dept Dermatol, New York, NY 10016 USA. [Loomis, Cynthia A.] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. [Duncan, Emma L.] Royal Brisbane & Womens Hosp, Dept Diabet & Endocrinol, Brisbane, Qld 4029, Australia. RP Richards, JB (reprint author), McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada. EM brent.richards@mcgill.ca RI Smith, Albert Vernon/K-5150-2015; Gardiner, Brooke/C-7773-2011; Fox, Laura /C-6249-2016; Oei, Ling/E-8163-2013; Reeve, Jonathan/C-7551-2012; Rosello Diez, Alberto/K-7295-2016; Davey Smith, George/A-7407-2013; Gudnason, Vilmundur/K-6885-2015 OI Kemp, John/0000-0002-9105-2249; Evans, David/0000-0003-0663-4621; Gregson, Celia/0000-0001-6414-0529; Timpson, Nicholas/0000-0002-7141-9189; Pettersson Kymmer, Ulrika/0000-0002-0557-9803; Forgetta, Vincenzo/0000-0002-6061-4720; van der Velde, Nathalie/0000-0002-6477-6209; Smith, Albert Vernon/0000-0003-1942-5845; Mellstrom, Dan/0000-0003-2761-3723; Farber, Charles/0000-0002-6748-4711; Soranzo, Nicole/0000-0003-1095-3852; Rivadeneira, Fernando/0000-0001-9435-9441; Karasik, David/0000-0002-8826-0530; Cheung, Warren/0000-0003-0267-7464; Vandenput, Liesbeth/0000-0002-1712-6131; McCarthy, Shane/0000-0002-2715-4187; Medina-Gomez, Carolina/0000-0001-7999-5538; Gardiner, Brooke/0000-0003-3740-3244; Moayyeri, Alireza/0000-0002-9143-2161; Oei, Ling/0000-0003-3523-458X; Kiel, Douglas/0000-0001-8474-0310; Center, Jacqueline/0000-0002-5278-4527; Reeve, Jonathan/0000-0002-4364-2682; Rosello Diez, Alberto/0000-0002-5550-9846; Davey Smith, George/0000-0002-1407-8314; McKechanie, Andrew/0000-0003-4273-9906; Williams, Stephen/0000-0003-2108-2757; Gudnason, Vilmundur/0000-0001-5696-0084 FU Arthritis Research UK [20000]; British Heart Foundation [RG/08/014/24067]; Canadian Institutes of Health Research [119462-1]; Medical Research Council [MC_UU_12013/1, G0401527, G1000143, MC_PC_15018, MC_UU_12013/3, MC_UU_12013/4, MR/L003120/1]; NCI NIH HHS [P30 CA008748, P30 CA015704, UM1 CA182913]; NIA NIH HHS [R01 AG005394, R01 AG005407, R01 AG027574, R01 AG027576, U01 AG018197, U01 AG042140, U01 AG042143]; NIAMS NIH HHS [K01 AR062655, P30 AR057235, R00 AR061430, R01 AR035582, R01 AR035583, R01 AR063702, RC2 AR058973, U01 AR045580, U01 AR045583, U01 AR045614, U01 AR045632, U01 AR045647, U01 AR045654, U01 AR066160]; Wellcome Trust [102215] NR 38 TC 39 Z9 39 U1 13 U2 52 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 OCT 1 PY 2015 VL 526 IS 7571 BP 112 EP + DI 10.1038/nature14878 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS5CY UT WOS:000362095100044 PM 26367794 ER PT J AU Takeda, S Wegmann, S Cho, HS Devos, SL Commins, C Roe, AD Nicholls, SB Carlson, GA Pitstick, R Nobuhara, CK Costantino, I Frosch, MP Muller, DJ Irimia, D Hyman, BT AF Takeda, Shuko Wegmann, Susanne Cho, Hansang Devos, Sarah L. Commins, Caitlin Roe, Allyson D. Nicholls, Samantha B. Carlson, George A. Pitstick, Rose Nobuhara, Chloe K. Costantino, Isabel Frosch, Matthew P. Mueller, Daniel J. Irimia, Daniel Hyman, Bradley T. TI Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain SO NATURE COMMUNICATIONS LA English DT Article ID IN-VIVO; NEUROFIBRILLARY TANGLES; MOUSE MODEL; EXTRACELLULAR TAU; ENDOGENOUS TAU; PATHOLOGY; TAUOPATHIES; OLIGOMERS; IDENTIFICATION; TRANSMISSION AB Tau pathology is known to spread in a hierarchical pattern in Alzheimer's disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development. C1 [Takeda, Shuko; Wegmann, Susanne; Devos, Sarah L.; Commins, Caitlin; Roe, Allyson D.; Nicholls, Samantha B.; Nobuhara, Chloe K.; Costantino, Isabel; Frosch, Matthew P.; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimers Dis Res Lab,MassGen Inst N, Charlestown, MA 02129 USA. [Cho, Hansang; Irimia, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. [Cho, Hansang] Univ N Carolina, Dept Mech Engn & Engn Sci, Charlotte, NC 28223 USA. [Carlson, George A.; Pitstick, Rose] McLaughlin Res Inst, Great Falls, MT 59405 USA. [Irimia, Daniel] ETH, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimers Dis Res Lab,MassGen Inst N, Charlestown, MA 02129 USA. EM BHYMAN@mgh.harvard.edu RI Muller, Daniel/A-5967-2010 OI Muller, Daniel/0000-0003-3075-0665 FU NIH [AG026249, P50AG05134, GM092804]; Massachusetts Life Sciences Center; JPB foundation; Japan Society for the Promotion of Science; German Research Foundation; BioMEMS Resource center [EB00002503] FX This research is supported by NIH Grants AG026249 and P50AG05134, the Massachusetts Life Sciences Center and The JPB foundation (B.T.H.); NIH GM092804 (D.I.). S.T. is supported by the fellowship from the Japan Society for the Promotion of Science. S.W. is supported by a fellowship from the German Research Foundation. All fabrication procedures of microfluidic devices were performed at the BioMEMS Resource center (grant EB00002503). We thank Dr. Mark I. Diamond for providing HEK-tau-biosensor cells. The authors declare no competing financial interests. NR 43 TC 18 Z9 18 U1 4 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2015 VL 6 AR 8490 DI 10.1038/ncomms9490 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW4DK UT WOS:000364941300002 PM 26458742 ER PT J AU Staller, K Barshop, K Kuo, B Ananthakrishnan, AN AF Staller, K. Barshop, K. Kuo, B. Ananthakrishnan, A. N. TI Resting anal pressure, not outlet obstruction or transit, predicts healthcare utilization in chronic constipation: a retrospective cohort analysis SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE anorectal manometry; chronic constipation; resting anal pressure; utilization ID IRRITABLE-BOWEL-SYNDROME; RESOLUTION ANORECTAL MANOMETRY; PELVIC FLOOR DYSSYNERGIA; FUNCTIONAL CONSTIPATION; CONTROLLED-TRIAL; NORMAL VALUES; INTRACTABLE CONSTIPATION; BIOFEEDBACK; DISORDERS; PRUCALOPRIDE AB Background Chronic constipation is common and exerts a considerable burden on health-related quality of life and healthcare resource utilization. Anorectal manometry (ARM) and colonic transit testing have allowed classification of subtypes of constipation, raising promise of targeted treatments. There has been limited study of the correlation between physiological parameters and healthcare utilization. Methods All patients undergoing ARM and colonic transit testing for chronic constipation at two tertiary care centers from 2000 to 2014 were included in this retrospective study. Our primary outcomes included number of constipation-related and gastroenterology visits per year. Multivariate linear regression adjusting for con-founders defined independent effect of measures of colonic and anorectal function on healthcare utilization. Key Results Our study included 612 patients with chronic constipation. More than 50% (n = 333) of patients had outlet obstruction by means of balloon expulsion testing and 43.5% (n = 266) had slow colonic transit. On unadjusted analysis, outlet obstruction (1.98 vs 1.68), slow transit (2.40 vs 2.07) and high resting anal pressure (2.16 vs 1.76) were all associated with greater constipation-related visits/year compared to patients without each of those parameters (p < 0.05 for all). Outlet obstruction and high resting anal pressure were also associated with greater number of gastroenterology visits/year. After multivariate adjustment, high resting anal pressure was the only independent predictor of increased constipation-related visits/year (p = 0.02) and gastroenterology visits/year (p = 0.04). Conclusions (sic) Inferences Among patients with chronic constipation, high resting anal pressure, rather than outlet obstruction or slow transit, predicts healthcare resource utilization. C1 [Staller, K.; Kuo, B.; Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Staller, K.; Kuo, B.; Ananthakrishnan, A. N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Barshop, K.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. RP Staller, K (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM kstaller@mgh.harvard.edu OI Staller, Kyle/0000-0003-4925-4290 FU National Institutes of Health [K23 DK097142] FX A Ananthakrishnan was supported by a grant from the National Institutes of Health (K23 DK097142). NR 44 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD OCT PY 2015 VL 27 IS 10 BP 1378 EP 1388 DI 10.1111/nmo.12628 PG 11 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA CW1KL UT WOS:000364748700004 PM 26172284 ER PT J AU Cheng, LS Hotta, R Graham, HK Nagy, N Goldstein, AM Belkind-Gerson, J AF Cheng, L. S. Hotta, R. Graham, H. K. Nagy, N. Goldstein, A. M. Belkind-Gerson, J. TI Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE cell therapy; endoscopy; enteric neural stem cells; enteric neuropathies; Hirschsprung disease ID TRANSPLANTATION; NEURONS; COLON; MICE; RAT; GUT AB Background Transplantation of enteric neural stem cells (ENSC) holds promise as a potential therapy for enteric neuropathies, including Hirschsprung disease. Delivery of transplantable cells via laparotomy has been described, but we propose a novel, minimally invasive endoscopic method of cell delivery. Methods Enteric neural stem cells for transplantation were cultured from dissociated gut of postnatal donor mice. Twelve recipient mice, including Ednrb(-/-) mice with distal colonic aganglionosis, underwent colonoscopic injection of ENSC under direct vision using a 30-gauge Hamilton needle passed through a rigid cystoureteroscope. Cell engraftment, survival, and neuroglial differentiation were studied 1-4 weeks after the procedure. Key Results All recipient mice tolerated the procedure without complications and survived to sacrifice. Transplanted cells were found within the colonic wall in 9 of 12 recipient mice with differentiation into enteric neurons and glia. Conclusions & Inferences Endoscopic injection of ENSC is a safe and reliable method for cell delivery, and can be used to deliver a large number of cells to a specific area of disease. This minimally invasive endoscopic approach may prove beneficial to future human applications of cell therapy for neurointestinal disease. C1 [Cheng, L. S.; Hotta, R.; Graham, H. K.; Nagy, N.; Goldstein, A. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA USA. [Cheng, L. S.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Nagy, N.] Semmelweis Univ, H-1085 Budapest, Hungary. [Goldstein, A. M.; Belkind-Gerson, J.] MassGen Hosp Children, Pediat Neurogastroenterol Program, Boston, MA USA. [Belkind-Gerson, J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA USA. RP Belkind-Gerson, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM jbelkindgerson@mgh.harvard.edu FU Society of University Surgeons; REACHirschsprung Foundation; National Institutes of Health [DK080914] FX LSC is supported by a resident scholar award from the Society of University Surgeons. RH is supported by a grant from the REACHirschsprung Foundation. AMG is supported by the National Institutes of Health (DK080914). NR 14 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD OCT PY 2015 VL 27 IS 10 BP 1509 EP 1514 DI 10.1111/nmo.12635 PG 6 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA CW1KL UT WOS:000364748700017 PM 26190543 ER PT J AU Santorino, D Siedner, MJ Mwanga-Amumpaire, J Shearer, MJ Harrington, DJ Wariyar, U AF Santorino, Data Siedner, Mark J. Mwanga-Amumpaire, Juliet Shearer, Martin J. Harrington, Dominic J. Wariyar, Unni TI Prevalence and Predictors of Functional Vitamin K Insufficiency in Mothers and Newborns in Uganda SO Nutrients LA English DT Article DE vitamin K; undercarboxylated prothrombin; deficiency; insufficiency; newborn; bleeding; haemorrhage; prophylaxis ID FETAL INTRACRANIAL HEMORRHAGE; DES-GAMMA-CARBOXYPROTHROMBIN; PRETERM INFANTS; HYPEREMESIS GRAVIDARUM; LACTATING MOTHERS; HUMAN-MILK; DEFICIENCY; DISEASE; PROTHROMBIN; PROPHYLAXIS AB Vitamin K deficiency bleeding (VKDB) in infancy is a serious but preventable cause of mortality or permanent disability. Lack of epidemiologic data for VKDB in sub-Saharan Africa hinders development and implementation of effective prevention strategies. We used convenience sampling to consecutively enroll mothers delivering in a southwestern Uganda Hospital. We collected socio-demographic and dietary information, and paired samples of maternal venous and neonatal cord blood for the immunoassay of undercarboxylated prothrombin (PIVKA-II), a sensitive marker of functional vitamin K (VK) insufficiency. We used univariable and multivariable logistic regression models to identify predictors of VK insufficiency. We detected PIVKA-II of 0.2 AU (Arbitrary Units per mL)/mL (indicative of VK insufficiency) in 33.3% (47/141) of mothers and 66% (93/141) of newborns. Importantly, 22% of babies had PIVKA-II concentrations 5.0 AU/mL, likely to be associated with abnormal coagulation indices. We found no significant predictors of newborn VK insufficiency, including infant weight (AOR (adjusted odds ratio) 1.85, 95% CI (confidence interval) 0.15-22.49), gender (AOR 0.54, 95% CI 0.26-1.11), term birth (AOR 0.72, 95% CI 0.20-2.62), maternal VK-rich diet (AOR 1.13, 95% CI 0.55-2.35) or maternal VK insufficiency (AOR 0.99, 95% CI 0.47-2.10). VK insufficiency is common among mothers and newborn babies in southwestern Uganda, which in one fifth of babies nears overt deficiency. Lack of identifiable predictors of newborn VK insufficiency support strategies for universal VK prophylaxis to newborns to prevent VKDB. C1 [Santorino, Data; Mwanga-Amumpaire, Juliet; Wariyar, Unni] Mbarara Univ Sci & Technol, Dept Pediat & Child Hlth, Mbarara, Uganda. [Siedner, Mark J.] Massachusetts Gen Hosp, Dept Med & Infect Dis, Boston, MA 02114 USA. [Siedner, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Shearer, Martin J.; Harrington, Dominic J.] St Thomas Hosp, Ctr Haemostasis & Thrombosis, London SE1 7EH, England. RP Santorino, D (reprint author), Mbarara Univ Sci & Technol, Dept Pediat & Child Hlth, Plot 8-18 Mbarara Kabale Rd,POB 1410, Mbarara, Uganda. EM boymukedata@gmail.com; MSIEDNER@mgh.harvard.edu; jmwanga@must.ac.ug; Martin.Shearer@gstt.nhs.uk; Dominic.Harrington@viapath.co.uk; wariyarunniwariyar@gmail.com FU Mbarara University of Science and Technology; German Academic Exchange Service; Centre for Haemostasis and Thrombosis, St. Thomas' Hospital, London FX We would like to thank Mbarara University of Science and Technology, The German Academic Exchange Service and the Centre for Haemostasis and Thrombosis, St. Thomas' Hospital, London for funding different aspects of this study either directly or indirectly. Additionally, we wish to thank Kieran Voong of the Centre for Haemostasis and Thrombosis, St Thomas' Hospital for performing the PIVKA-II assays. NR 35 TC 1 Z9 1 U1 1 U2 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD OCT PY 2015 VL 7 IS 10 BP 8545 EP 8552 DI 10.3390/nu7105408 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CV4IZ UT WOS:000364231700023 PM 26501317 ER PT J AU Elisei, R Schlumberger, M Tahara, M Robinson, B Brose, M Dutcus, C Zhu, J Newbold, K Kiyota, N Kim, SB Sherman, S Wirth, L AF Elisei, R. Schlumberger, M. Tahara, M. Robinson, B. Brose, M. Dutcus, C. Zhu, J. Newbold, K. Kiyota, N. Kim, S. -B. Sherman, S. Wirth, L. TI Subgroup analysis according to differentiated thyroid cancer histology in phase 3 (SELECT) trial of lenvatinib SO Oncology Research and Treatment LA English DT Meeting Abstract C1 [Elisei, R.] Univ Pisa, Dept Clin & Expt Med, Endocrine Unit, Pisa, Italy. [Schlumberger, M.] Gustave Roussy, Dept Nucl Med & Endocrine Oncol, Villejuif, France. [Schlumberger, M.] Univ Paris 11, Villejuif, France. [Tahara, M.] Natl Canc Ctr Hosp East, Dept Head & Neck Med Oncol, Kashiwa, Chiba, Japan. [Robinson, B.] Univ Sydney, Kolling Inst Med Res, Sydney, NSW 2006, Australia. [Brose, M.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Dutcus, C.; Zhu, J.] Eisai Inc, Woodcliff Lake, NJ USA. [Newbold, K.] Royal Marsden Natl Hlth Serv Trust, London, England. [Kiyota, N.] Kobe Univ Hosp, Dept Med Oncol & Hematol, Kobe, Hyogo, Japan. [Kim, S. -B.] Univ Ulsan, Coll Med, Dept Oncol, Asan Med Ctr, Seoul, South Korea. [Sherman, S.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Div Internal Med, Houston, TX 77030 USA. [Wirth, L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RI Kiyota, Naomi/K-3226-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA V91 BP 25 EP 26 PG 2 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800053 ER PT J AU Stilgenbauer, S Jones, JA Coutre, SE Mato, AR Hillmen, P Tam, C Osterborg, A Siddiqi, T Thirman, MJ Furman, RR Ilhan, O Keating, M Call, TG Brown, JR Stevens-Brogan, M Li, Y Clow, F James, DF Chu, AD Hallek, M O'Brien, S AF Stilgenbauer, S. Jones, J. A. Coutre, S. E. Mato, A. R. Hillmen, P. Tam, C. Osterborg, A. Siddiqi, T. Thirman, M. J. Furman, R. R. Ilhan, O. Keating, M. Call, T. G. Brown, J. R. Stevens-Brogan, M. Li, Y. Clow, F. James, D. F. Chu, A. D. Hallek, M. O'Brien, S. TI Results from the phase 2 RESONATE (TM)-17 trial: Efficacy and safety of Ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma with Del17p SO Oncology Research and Treatment LA English DT Meeting Abstract C1 [Stilgenbauer, S.] Univ Ulm, D-89069 Ulm, Germany. [Jones, J. A.] Ohio State Univ, Div Hematol, Columbus, OH 43210 USA. [Coutre, S. E.] Stanford Univ, Sch Med, Div Hematol, Stanford Canc Ctr, Stanford, CA 94305 USA. [Mato, A. R.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Hillmen, P.] Leeds Teaching Hosp, St James Inst Onco, Leeds, W Yorkshire, England. [Tam, C.] Peter MacCallum Canc Ctr, East Melbourne, Australia. [Osterborg, A.] Karolinska Univ Hosp Solna, Dept Hematol, Solna, Sweden. [Siddiqi, T.] City Hope Natl Med Ctr, Dept Hematol Hematopoiet Cell Transplantat, Duarte, CA 91010 USA. [Thirman, M. J.] Univ Chicago Med, Hematol Oncol Sect, Chicago, IL USA. [Furman, R. R.] Weill Cornell Med Coll, Div Hematol Oncol, New York, NY USA. [Ilhan, O.] Ankara Univ, Fac Med, TR-06100 Ankara, Turkey. [Keating, M.; O'Brien, S.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Call, T. G.] Mayo Clin, Div Hematol, Rochester, MN USA. [Brown, J. R.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Stevens-Brogan, M.; Li, Y.; Clow, F.; James, D. F.; Chu, A. D.] Pharmacyclics Inc, Sunnyvale, CA USA. [Hallek, M.] Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany. [Hallek, M.] Ctr Integrated Oncol Cologne Bonn, Cologne, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA V291 BP 92 EP 92 PG 1 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800213 ER PT J AU Bashari, MH Fan, F Vallet, S Arn, M Cardone, MH Beckhove, P Schneeweiss, A Sattler, M Opferman, JT Jager, D Podar, K AF Bashari, M. H. Fan, F. Vallet, S. Arn, M. Cardone, M. H. Beckhove, P. Schneeweiss, A. Sattler, M. Opferman, J. T. Jaeger, D. Podar, K. TI Mcl-1 confers protection of HER2+breast cancer cells exposed to hypoxia: Therapeutic implications SO Oncology Research and Treatment LA English DT Meeting Abstract C1 [Bashari, M. H.; Fan, F.; Vallet, S.; Schneeweiss, A.; Jaeger, D.; Podar, K.] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Med Oncol, Heidelberg, Germany. [Arn, M.; Cardone, M. H.] Eutrop Pharmaceut Inc, Cambridge, MA USA. [Beckhove, P.] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Beckhove, P.] German Canc Res Ctr, Heidelberg, Germany. [Sattler, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Opferman, J. T.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Jaeger, D.] German Canc Res Ctr, Appl Tumor Immun, Heidelberg, Germany. RI Bashari, Muhammad Hasan/H-7079-2016 OI Bashari, Muhammad Hasan/0000-0001-7298-0317 NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA V431 BP 124 EP 124 PG 1 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800294 ER PT J AU Raab, MS Richardson, PG Jagannath, S Moreau, P Jakubowiak, AJ Facon, T Vij, R White, D Reece, DE Benboubker, L Zonder, J Tsao, LC Anderson, KC Bleickardt, E Singhal, AK Lonial, S AF Raab, M. S. Richardson, P. G. Jagannath, S. Moreau, P. Jakubowiak, A. J. Facon, T. Vij, R. White, D. Reece, D. E. Benboubker, L. Zonder, J. Tsao, L. C. Anderson, K. C. Bleickardt, E. Singhal, A. K. Lonial, S. TI Final results for the 1703 phase 1b/2 study of Elotuzumab (Elo) in combination with Lenalidomide (Len) and dexamethasone (dex) in patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM) SO Oncology Research and Treatment LA English DT Meeting Abstract C1 [Raab, M. S.] Univ Klinikum, Heidelberg, Germany. [Richardson, P. G.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Richardson, P. G.; Jagannath, S.; Jakubowiak, A. J.; Vij, R.; Zonder, J.; Anderson, K. C.; Lonial, S.] Multiple Myeloma Res Consortium, Norwalk, CT USA. [Jagannath, S.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Moreau, P.] Univ Hosp, Nantes, France. [Jakubowiak, A. J.] Univ Chicago, Chicago, IL 60637 USA. [Facon, T.] Hop Claude Huriez, Lille, France. [Vij, R.] Washington Univ, Sch Med, St Louis, MO USA. [White, D.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Reece, D. E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Benboubker, L.] CHU Tours Hop Bretonneau, Tours, France. [Zonder, J.] Karmanos Canc Inst, Detroit, MI USA. [Tsao, L. C.; Singhal, A. K.] AbbVie Biotherapeut Inc ABR, Redwood City, CA USA. [Bleickardt, E.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Lonial, S.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 1 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA V548 BP 165 EP 165 PG 1 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800398 ER PT J AU Schoffski, P Maki, R Italiano, A Gelderblom, H Choy, E Grignani, G Camargo, V Bauer, S Rha, SY Chawla, S Blay, JY Hohenberger, P D'Adamo, D Chen, R Chmielowski, B Le Cesne, A George, D Patel, S AF Schoeffski, P. Maki, R. Italiano, A. Gelderblom, H. Choy, E. Grignani, G. Camargo, V Bauer, S. Rha, S. Y. Chawla, S. Blay, J-Y Hohenberger, P. D'Adamo, D. Chen, R. Chmielowski, B. Le Cesne, A. George, D. Patel, S. TI Randomized, open-label, multicenter, phase 3 study of eribulin versus dacarbazine in patients (pts) with leiomyosarcoma (LMS) and adipocytic sarcoma (ADI) SO Oncology Research and Treatment LA English DT Meeting Abstract C1 [Schoeffski, P.] Katholieke Univ Leuven Hosp, Dept Gen Med Oncol, Leuven, Belgium. [Maki, R.] Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA. [Italiano, A.] Inst Bergonie, Dept Oncol, Bordeaux, France. [Gelderblom, H.] Leiden Univ, Med Ctr, Dept Med Oncol, Leiden, Netherlands. [Choy, E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Grignani, G.] Fdn Piemonte Oncol IRCC, Dept Med Oncol, Candiolo, Italy. [Camargo, V] Hosp Sirio Libanes, Dept Med Oncol, Sau Paulo, Brazil. [Bauer, S.] West German Canc Ctr, Essen, Germany. [Rha, S. Y.] Severance Hosp, Sinchon Dong, South Korea. [Chawla, S.] Sarcoma Oncol Ctr, Santa Monica, CA USA. [Blay, J-Y] Univ Lyon 1, F-69365 Lyon, France. [Blay, J-Y] Ctr Leon Berard, F-69373 Lyon, France. [Hohenberger, P.] Univ Mannheim, Med Ctr, Div Surg Oncol & Thorac Surg, Dept Surg, D-68131 Mannheim, Germany. [D'Adamo, D.; Chen, R.] Eisai Inc, Woodcliff Lake, NJ USA. [Chmielowski, B.] Univ Calif Los Angeles, Dept Hematol, Jonsson Comprehens Canc, Los Angeles, CA USA. [Le Cesne, A.] Gustave Roussy, Villejuif, France. [George, D.] Dana Farber Canc Inst, Sarcoma Ctr, Boston, MA 02115 USA. [George, D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [George, D.] Harvard Univ, Sch Med, Boston, MA USA. [Patel, S.] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA V579 BP 174 EP 174 PG 1 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800421 ER PT J AU Konantz, M Muller, J Lenard, A Alghisi, E Esain, V Carroll, KJ North, TE Lengerke, C AF Konantz, M. Mueller, J. Lenard, A. Alghisi, E. Esain, V Carroll, K. J. North, T. E. Lengerke, C. TI The zebrafish homologue of the murine Evi1 gene critically regulates HSC development via the NOTCH pathway SO Oncology Research and Treatment LA English DT Meeting Abstract C1 [Konantz, M.; Mueller, J.; Lenard, A.; Alghisi, E.; Lengerke, C.] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland. [Esain, V; Carroll, K. J.; North, T. E.] Harvard Univ, Sch Med, Dept Pathol, BIDMC, Boston, MA 02115 USA. [Lengerke, C.] Univ Basel Hosp, Clin Hematol, CH-4031 Basel, Switzerland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA V582 BP 175 EP 176 PG 2 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800424 ER PT J AU le Coutre, PD Cortes, JE Kim, DW Pinilla-Ibarz, J Paquette, R Chuah, C Nicolini, FE Apperley, JF Khoury, HJ Talpaz, M DeAngelo, DJ Abruzzese, E Rea, D Baccarani, M Muller, MC Gambacorti-Passerini, C Lustgarten, S Rivera, VM Clackson, T Haluska, FG Guilhot, F Deininger, MW Hochhaus, A Hughes, TP Shah, NP Kantarjian, HM AF le Coutre, P. D. Cortes, J. E. Kim, D. -W Pinilla-Ibarz, J. Paquette, R. Chuah, C. Nicolini, F. E. Apperley, J. F. Khoury, H. J. Talpaz, M. DeAngelo, D. J. Abruzzese, E. Rea, D. Baccarani, M. Mueller, M. C. Gambacorti-Passerini, C. Lustgarten, S. Rivera, V. M. Clackson, T. Haluska, F. G. Guilhot, F. Deininger, M. W. Hochhaus, A. Hughes, T. P. Shah, N. P. Kantarjian, H. M. TI Ponatinib efficacy and safety in heavily pretreated leukemia patients (Pts) in the PACE trial at 3 years SO Oncology Research and Treatment LA English DT Meeting Abstract C1 [le Coutre, P. D.] Charite, D-13353 Berlin, Germany. [Cortes, J. E.; Kantarjian, H. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kim, D. -W] Catholic Univ Korea, Seoul St Marys Hosp, Seoul, South Korea. [Pinilla-Ibarz, J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Paquette, R.] Univ Calif Los Angeles, Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Chuah, C.] Singapore Gen Hosp, Singapore, Singapore. [Chuah, C.] Duke Natl Univ Singapore Grad Med Sch, Singapore, Singapore. [Nicolini, F. E.] Ctr Hosp Lyon Sud, Lyon, France. [Apperley, J. F.] Univ London Imperial Coll Sci Technol & Med, Ctr Haematol, London SW7 2AZ, England. [Khoury, H. J.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Talpaz, M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [DeAngelo, D. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abruzzese, E.] Univ Roma Tor Vergata, S Eugenio Hosp, Rome, Italy. [Rea, D.] Hop St Louis, Paris, France. [Baccarani, M.] Univ Bologna, Bologna, Italy. [Mueller, M. C.] Univ Med, Mannheim, Germany. [Gambacorti-Passerini, C.] Univ Milano Bicocca, Azienda Osped San Gerardo, Monza, Italy. [Lustgarten, S.; Rivera, V. M.; Clackson, T.; Haluska, F. G.] ARIAD Pharmaceut Inc, Cambridge, MA USA. [Guilhot, F.] CHU Poitiers, Inserm CIC 1402, Poitiers, France. [Deininger, M. W.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Hochhaus, A.] Jena Univ Hosp, Jena, Germany. [Hughes, T. P.] Univ Adelaide, Adelaide, SA, Australia. [Hughes, T. P.] South Australian Hlth & Med Res Inst, Adelaide, SA, Australia. [Shah, N. P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA V604 BP 182 EP 183 PG 2 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800437 ER PT J AU Motzer, R Hutson, T Glen, H Michaelson, MD Molina, A Eisen, T Jassem, J Zolnierek, J Maroto, P Mellado, B Melichar, B Tomasek, J Kim, HJ Wood, K Dutcus, C Larkin, J AF Motzer, R. Hutson, T. Glen, H. Michaelson, M. D. Molina, A. Eisen, T. Jassem, J. Zolnierek, J. Maroto, P. Mellado, B. Melichar, B. Tomasek, J. Kim, H. -J. Wood, K. Dutcus, C. Larkin, J. TI Randomized phase 2 three-arm trial of lenvatinib (LEN), everolimus (EVE), and LEN plus EVE in patients (pts) with metastatic renal cell carcinoma (mRCC) SO Oncology Research and Treatment LA English DT Meeting Abstract C1 [Motzer, R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hutson, T.] Texas Oncol, Dallas, TX USA. [Glen, H.] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Molina, A.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Eisen, T.] Addenbrookes Hosp, Cambridge Biomed Res Ctr, Cambridge, England. [Jassem, J.] Med Univ Gdansk, Gdansk, Poland. [Zolnierek, J.] Inst Warszawie, Ctr Onkol, Warsaw, Poland. [Maroto, P.] Dept Med Oncol, Barcelona, Spain. [Mellado, B.] Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain. [Melichar, B.] Univ Palackeho, Lekarska Fak, Onkol Klin, Fak Nemocnice, Olomouc, Czech Republic. [Tomasek, J.] Masaryk Univ, Masaryk Mem Canc Inst, Brno, Czech Republic. [Kim, H. -J.; Dutcus, C.] Eisai Inc, Woodcliff Lake, NJ USA. [Wood, K.] Eisai Ltd, Hatfield, Herts, England. [Larkin, J.] Royal Marsden NHS Hosp, London, England. NR 0 TC 0 Z9 0 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA V673 BP 203 EP 204 PG 2 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800489 ER PT J AU Grunwald, V Demetri, GD Reichardt, P Kang, YK Blay, JY Joensuu, H Schafer, K Kuss, I Kappeler, C Casali, PG AF Gruenwald, V Demetri, G. D. Reichardt, P. Kang, Y. -K Blay, J-Y Joensuu, H. Schaefer, K. Kuss, I Kappeler, C. Casali, P. G. 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 Oncology Research and Treatment LA English DT Meeting Abstract C1 [Gruenwald, V] Hannover Med Sch, Klin Hamatol Hamostaseol Onkol & Stammzelltranspl, D-30623 Hannover, Germany. [Demetri, G. D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Demetri, G. D.] Harvard Univ, Sch Med, Boston, MA USA. [Reichardt, P.] HELIOS Klin, Berlin, Germany. [Kang, Y. -K] Univ Ulsan, Coll Med, Seoul, South Korea. [Joensuu, H.] Ctr Leon Berard, F-69373 Lyon, France. [Joensuu, H.] Univ Lyon 1, F-69365 Lyon, France. [Schaefer, K.; Kuss, I; Kappeler, C.] Helsinki Univ Cent Hosp, Helsinki, Finland. [Casali, P. G.] Natl Canc Ctr Hosp EastInst, Milan, Italy. RI Schafer, Katrin/P-4728-2015; 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 KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA P803 BP 245 EP 246 PG 2 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800592 ER PT J AU Berghaus, K Zhang, JT Yun, SH Scarcelli, G AF Berghaus, Kim Zhang, Jitao Yun, Seok H. Scarcelli, Giuliano TI High-finesse sub-GHz-resolution spectrometer employing VIPA etalons of different dispersion SO OPTICS LETTERS LA English DT Article ID BRILLOUIN SPECTROSCOPY; SCATTERING; LENS AB We report a novel configuration of a two-stage virtually imaged phased array spectrometer that enables high-throughput sub-GHz spectroscopy at a high finesse (>750). Two etalons with different free spectral range and different dispersion are arranged in an orthogonal direction and spread the spectrum across two dimensions, with a greatly improved rejection ratio of white-light background noise. A proof-of-concept application for Brillouin spectroscopy is demonstrated. (C) 2015 Optical Society of America C1 [Berghaus, Kim; Yun, Seok H.; Scarcelli, Giuliano] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Berghaus, Kim; Yun, Seok H.; Scarcelli, Giuliano] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Berghaus, Kim; Zhang, Jitao; Scarcelli, Giuliano] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. RP Scarcelli, G (reprint author), Harvard Univ, Sch Med, 65 Landsdowne St, Cambridge, MA 02139 USA. EM scarc@umd.edu FU Human Frontier Science Program (HFSP); MSIP (Ministry of Science, ICT and Future Planning), Korea, "ICT Consilience Creative Program" [IITP-2015-R0346-15-1007]; National Eye Institute (NEI) [R21 EY023043]; National Institute of Biomedical Imaging and Bioengineering (NIBIB) [K25 EB015885, P41 EB015903] FX Human Frontier Science Program (HFSP) (Young Investigator Grant); MSIP (Ministry of Science, ICT and Future Planning), Korea, "ICT Consilience Creative Program" (IITP-2015-R0346-15-1007); National Eye Institute (NEI) (R21 EY023043); National Institute of Biomedical Imaging and Bioengineering (NIBIB) (K25 EB015885, P41 EB015903). NR 14 TC 5 Z9 5 U1 4 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD OCT 1 PY 2015 VL 40 IS 19 BP 4436 EP 4439 DI 10.1364/OL.40.004436 PG 4 WC Optics SC Optics GA CV7QB UT WOS:000364468000015 PM 26421550 ER PT J AU Banks, WA AF Banks, William A. TI Peptides and the blood-brain barrier SO PEPTIDES LA English DT Article DE Peptides; Blood-brain barrier; AJ Kastin; Delta sleep-inducing peptide; Regulatory proteins; Cytokines ID CARRIER-MEDIATED TRANSPORT; DSIP PEPTIDES; AMINO-ACIDS; RAT-BRAIN; SATURABLE SYSTEM; PERMEABILITY; TYR-MIF-1; PENETRATION; CROSSES; ALPHA AB The demonstration that peptides and regulatory proteins can cross the blood-brain barrier (BBB) is one of the major contributions of Dr. Abba J. Kastin. He was the first to propose that peptides could cross the BBB, the first to show that an endogenous peptide did so, and the first to describe a saturable transport system at the BBB for peptides. His work shows that in crossing the BBB, peptides and regulatory proteins act as informational molecules, informing the brain of peripheral events. Brain-to-blood passage helps to control levels of peptides with the brain and can deliver information in the brain-to-blood direction. He showed that the transporters for peptides and proteins are not static, but respond to developmental and physiological changes and are affected by disease states. As such, the BBB is adaptive to the needs of the CNS, but when that adaption goes awry, the BBB can be a cause of disease. The mechanisms by which peptides and proteins cross the BBB offer opportunities for drug delivery of these substances or their analogs to the brain in the treatment of diseases of the central nervous system. Published by Elsevier Inc. C1 [Banks, William A.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA. [Banks, William A.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Banks, WA (reprint author), Rm810A Bldg 1,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU Veterans Affairs FX Supported by Veterans Affairs. NR 50 TC 5 Z9 5 U1 2 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD OCT PY 2015 VL 72 BP 16 EP 19 DI 10.1016/j.peptides.2015.03.010 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA CW0SO UT WOS:000364699900003 PM 25805003 ER PT J AU Hochner, H Allard, C Granot-Hershkovitz, E Chen, JB Sitlani, CM Sazdovska, S Lumley, T McKnight, B Rice, K Enquobahrie, DA Meigs, JB Kwok, P Hivert, MF Borecki, IB Gomez, F Wang, T van Duijn, C Amin, N Rotter, JI Stamatoyannopoulos, J Meiner, V Manor, O Dupuis, J Friedlander, Y Siscovick, DS AF Hochner, Hagit Allard, Catherine Granot-Hershkovitz, Einat Chen, Jinbo Sitlani, Colleen M. Sazdovska, Sandra Lumley, Thomas McKnight, Barbara Rice, Kenneth Enquobahrie, Daniel A. Meigs, James B. Kwok, Pui Hivert, Marie-France Borecki, Ingrid B. Gomez, Felicia Wang, Ting van Duijn, Cornelia Amin, Najaf Rotter, Jerome I. Stamatoyannopoulos, John Meiner, Vardiella Manor, Orly Dupuis, Josee Friedlander, Yechiel Siscovick, David S. TI Parent-of-Origin Effects of the APOB Gene on Adiposity in Young Adults SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; CORONARY-ARTERY-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; NUMBER TANDEM REPEAT; APOLIPOPROTEIN-B; OFFSPRING TRIOS; CARDIOVASCULAR-DISEASE; MISSING HERITABILITY; QUANTITATIVE TRAIT AB Loci identified in genome-wide association studies (GWAS) of cardio-metabolic traits account for a small proportion of the traits' heritability. To date, most association studies have not considered parent-of-origin effects (POEs). Here we report investigation of POEs on adiposity and glycemic traits in young adults. The Jerusalem Perinatal Family Follow-Up Study (JPS), comprising 1250 young adults and their mothers was used for discovery. Focusing on 18 genes identified by previous GWAS as associated with cardio-metabolic traits, we used linear regression to examine the associations of maternally- and paternally-derived offspring minor alleles with body mass index (BMI), waist circumference (WC), fasting glucose and insulin. We replicated and meta-analyzed JPS findings in individuals of European ancestry aged <= 50 belonging to pedigrees from the Framingham Heart Study, Family Heart Study and Erasmus Rucphen Family study (total N congruent to 4800). We considered p<2.7x10(-4) statistically significant to account for multiple testing. We identified a common coding variant in the 4th exon of APOB (rs1367117) with a significant maternally-derived effect on BMI (beta = 0.8; 95% CI: 0.4,1.1; p = 3.1x10(-5)) and WC (beta = 2.7; 95% CI: 1.7,3.7; p = 2.1x10(-7)). The corresponding paternally-derived effects were non-significant (p>0.6). Suggestive maternally-derived associations of rs1367117 were observed with fasting glucose (beta = 0.9; 95% CI: 0.3,1.5; p = 4.0x10(-3)) and insulin (ln-transformed, beta = 0.06; 95% CI: 0.03,0.1; p = 7.4x10(-4)). Bioinformatic annotation for rs1367117 revealed a variety of regulatory functions in this region in liver and adipose tissues and a 50% methylation pattern in liver only, consistent with allelic-specific methylation, which may indicate tissue-specific POE. Our findings demonstrate a maternal-specific association between a common APOB variant and adiposity, an association that was not previously detected in GWAS. These results provide evidence for the role of regulatory mechanisms, POEs specifically, in adiposity. In addition this study highlights the benefit of utilizing family studies for deciphering the genetic architecture of complex traits. C1 [Hochner, Hagit; Granot-Hershkovitz, Einat; Sazdovska, Sandra; Manor, Orly; Friedlander, Yechiel] Hebrew Univ Jerusalem, Hadassah Med Ctr, Braun Sch Publ Hlth, Jerusalem, Israel. [Allard, Catherine] Univ Sherbrooke, Dept Math, Sherbrooke, PQ J1K 2R1, Canada. [Allard, Catherine] CHU Sherbrooke, Ctr Rech, Sherbrooke, PQ J1H 5N4, Canada. [Chen, Jinbo] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Sitlani, Colleen M.; Stamatoyannopoulos, John] Univ Washington, Dept Med, Seattle, WA USA. [Sitlani, Colleen M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand. [McKnight, Barbara; Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Enquobahrie, Daniel A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Kwok, Pui] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Kwok, Pui] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Kwok, Pui] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Hivert, Marie-France] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Borecki, Ingrid B.; Gomez, Felicia; Wang, Ting] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [van Duijn, Cornelia; Amin, Najaf] Univ Med Ctr, Erasmus Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Dept Pediat, Torrance, CA 90509 USA. [Stamatoyannopoulos, John] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Meiner, Vardiella] Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Genet & Metab, Jerusalem, Israel. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. RP Hochner, H (reprint author), Hebrew Univ Jerusalem, Hadassah Med Ctr, Braun Sch Publ Hlth, Jerusalem, Israel. EM hagit.hochner@gmail.com FU National Institutes of Health research grant [R01HL088884]; Israeli Science Foundation [1252/07, 552/12]; NUS-HUJ CREATE Programme of the National Research Foundation, Singapore [370062002]; National Institute for Diabetes and Digestive and Kidney Diseases [2R01DK078616, K24 DK080140]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195, N02-HL-6-4278]; National Institute for Diabetes and Digestive and Kidney Diseases grant [R01DK8925601]; Netherlands Organization for Scientific Research (NWO) [91203014]; Center of Medical Systems Biology (CMSB); Hersenstichting Nederland; Internationale Stichting Alzheimer Onderzoek (ISAO); Alzheimer Association [04516]; Hersenstichting Nederland [12F04(2).76]; Interuniversity Attraction Poles (IUAP) program; European Commission FP6 STRP grant [018947, LSHG-CT-2006-01947]; European Community [HEALTH-F4-2007-201413]; European Commission under the programme "Quality of Life and Management of the Living Resources" of 5th Framework Programme [QLG2-CT-2002-01254]; Netherlands Organization for Scientific Research and the Russian Foundation for Basic Research [NWO-RFBR 047.017.043]; ZonMw grant [91111025]; BBMRI-NL FX JPS was supported by National Institutes of Health research grant (R01HL088884 DSS), the Israeli Science Foundation grants (Numbers 1252/07, 552/12 YF) and partly by the NUS-HUJ CREATE Programme of the National Research Foundation, Singapore (Project Number 370062002 YF). FamHS was supported by National Institute for Diabetes and Digestive and Kidney Diseases (2R01DK078616, K24 DK080140 JBM), and the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract Nos. N01-HC-25195, N02-HL-6-4278). FamHS was partly supported by National Institute for Diabetes and Digestive and Kidney Diseases grant (R01DK8925601 IBB). ERF Study was supported by the joint grant from the Netherlands Organization for Scientific Research (NWO, 91203014), the Center of Medical Systems Biology (CMSB), Hersenstichting Nederland, Internationale Stichting Alzheimer Onderzoek (ISAO), Alzheimer Association project number 04516, Hersenstichting Nederland project number 12F04(2).76, and the Interuniversity Attraction Poles (IUAP) program. As a part of EUROSPAN (European Special Populations Research Network) ERF was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme "Quality of Life and Management of the Living Resources" of 5th Framework Programme (no. QLG2-CT-2002-01254). High-throughput analysis of the ERF data was supported by joint grant from Netherlands Organization for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). Exome sequencing analysis in ERF was supported by the ZonMw grant (project 91111025). Exome-chip genotyping was supported by BBMRI-NL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 94 TC 1 Z9 1 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2015 VL 11 IS 10 AR e1005573 DI 10.1371/journal.pgen.1005573 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA CV6SU UT WOS:000364401600038 PM 26451733 ER PT J AU Won, HH Natarajan, P Dobbyn, A Jordan, DM Roussos, P Lage, K Raychaudhuri, S Stahl, E Do, R AF Won, Hong-Hee Natarajan, Pradeep Dobbyn, Amanda Jordan, Daniel M. Roussos, Panos Lage, Kasper Raychaudhuri, Soumya Stahl, Eli Do, Ron TI Disproportionate Contributions of Select Genomic Compartments and Cell Types to Genetic Risk for Coronary Artery Disease SO PLoS Genetics LA English DT Article ID WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; HEART-DISEASE; GENOTYPE IMPUTATION; COMMON DISEASES; WEIGHT-LOSS; HERITABILITY; VARIANTS; SUSCEPTIBILITY; SNPS AB Large genome-wide association studies (GWAS) have identified many genetic loci associated with risk for myocardial infarction (MI) and coronary artery disease (CAD). Concurrently, efforts such as the National Institutes of Health (NIH) Roadmap Epigenomics Project and the Encyclopedia of DNA Elements (ENCODE) Consortium have provided unprecedented data on functional elements of the human genome. In the present study, we systematically investigate the biological link between genetic variants associated with this complex disease and their impacts on gene function. First, we examined the heritability of MI/CAD according to genomic compartments. We observed that single nucleotide polymorphisms (SNPs) residing within nearby regulatory regions show significant polygenicity and contribute between 59-71% of the heritability for MI/CAD. Second, we showed that the polygenicity and heritability explained by these SNPs are enriched in histone modification marks in specific cell types. Third, we found that a statistically higher number of 45 MI/CAD-associated SNPs that have been identified from large-scale GWAS studies reside within certain functional elements of the genome, particularly in active enhancer and promoter regions. Finally, we observed significant heterogeneity of this signal across cell types, with strong signals observed within adipose nuclei, as well as brain and spleen cell types. These results suggest that the genetic etiology of MI/CAD is largely explained by tissue-specific regulatory perturbation within the human genome. C1 [Won, Hong-Hee; Natarajan, Pradeep] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Won, Hong-Hee; Natarajan, Pradeep] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Won, Hong-Hee; Natarajan, Pradeep; Lage, Kasper] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Won, Hong-Hee; Natarajan, Pradeep; Lage, Kasper; Raychaudhuri, Soumya; Stahl, Eli; Do, Ron] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Dobbyn, Amanda; Jordan, Daniel M.; Roussos, Panos; Stahl, Eli; Do, Ron] Icahn Sch Med Mt Sinai, Dept Genet & Gen, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Jordan, Daniel M.; Do, Ron] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Roussos, Panos; Stahl, Eli] Icahn Sch Med Mt Sinai, Div Psychiat Gen, New York, NY 10029 USA. [Lage, Kasper] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lage, Kasper] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester, Lancs, England. [Stahl, Eli; Do, Ron] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Ctr Stat Genet, New York, NY 10029 USA. [Do, Ron] Icahn Sch Med Mt Sinai, Zena & Michael Weiner Cardiovasc Inst, New York, NY 10029 USA. RP Won, HH (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM eli.stahl@mssm.edu; ron.do@mssm.edu RI Roussos, Panos/J-7090-2013; OI Roussos, Panos/0000-0002-4640-6239; Natarajan, Pradeep/0000-0001-8402-7435; Jordan, Daniel/0000-0002-5318-8225 FU Banting Fellowship from the Canadian Institutes of Health Research; postdoctoral award from the American Heart Association [15POST23280019]; John S. LaDue Memorial Fellowship in Cardiology from Harvard Medical School; Doris Duke Foundation; National Institutes of Health [1U01HG0070033, 5U01GM092691-04] FX RD was supported by a Banting Fellowship from the Canadian Institutes of Health Research. HHW is supported by a postdoctoral award from the American Heart Association (15POST23280019). PN is supported by the John S. LaDue Memorial Fellowship in Cardiology from Harvard Medical School. SR is supported by funding from the Doris Duke Foundation, and by the National Institutes of Health (1U01HG0070033, 5U01GM092691-04). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 5 Z9 5 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2015 VL 11 IS 10 AR e1005622 DI 10.1371/journal.pgen.1005622 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA CV6SU UT WOS:000364401600080 PM 26509271 ER PT J AU Rodriguez, RM Langdorf, MI Nishijima, D Baumann, BM Hendey, GW Medak, AJ Raja, AS Allen, IE Mower, WR AF Rodriguez, Robert M. Langdorf, Mark I. Nishijima, Daniel Baumann, Brigitte M. Hendey, Gregory W. Medak, Anthony J. Raja, Ali S. Allen, Isabel E. Mower, William R. TI Derivation and Validation of Two Decision Instruments for Selective Chest CT in Blunt Trauma: A Multicenter Prospective Observational Study (NEXUS Chest CT) SO PLOS MEDICINE LA English DT Article ID COMPUTED-TOMOGRAPHY; X-RAY; EMERGENCY-MEDICINE; CANCER-RISKS; RADIATION; INJURY; PATIENT; EXPERIENCE; MANAGEMENT; RADIOLOGY AB Background Unnecessary diagnostic imaging leads to higher costs, longer emergency department stays, and increased patient exposure to ionizing radiation. We sought to prospectively derive and validate two decision instruments (DIs) for selective chest computed tomography (CT) in adult blunt trauma patients. Methods and Findings From September 2011 to May 2014, we prospectively enrolled blunt trauma patients over 14 y of age presenting to eight US, urban level 1 trauma centers in this observational study. During the derivation phase, physicians recorded the presence or absence of 14 clinical criteria before viewing chest imaging results. We determined injury outcomes by CT radiology readings and categorized injuries as major or minor according to an expert-panel-derived clinical classification scheme. We then employed recursive partitioning to derive two DIs: Chest CT-All maximized sensitivity for all injuries, and Chest CT-Major maximized sensitivity for only major thoracic injuries (while increasing specificity). In the validation phase, we employed similar methodology to prospectively test the performance of both DIs. We enrolled 11,477 patients-6,002 patients in the derivation phase and 5,475 patients in the validation phase. The derived Chest CT-All DI consisted of (1) abnormal chest X-ray, (2) rapid deceleration mechanism, (3) distracting injury, (4) chest wall tenderness, (5) sternal tenderness, (6) thoracic spine tenderness, and (7) scapular tenderness. The Chest CT-Major DI had the same criteria without rapid deceleration mechanism. In the validation phase, Chest CT-All had a sensitivity of 99.2%(95% CI 95.4%-100%), a specificity of 20.8% (95% CI 19.2%-22.4%), and a negative predictive value (NPV) of 99.8% (95% CI 98.9%-100%) for major injury, and a sensitivity of 95.4% (95% CI 93.6%-96.9%), a specificity of 25.5% (95% CI 23.5%-27.5%), and a NPV of 93.9%(95% CI 91.5%-95.8%) for either major or minor injury. Chest CT-Major had a sensitivity of 99.2%(95% CI 95.4%100%), a specificity of 31.7%(95% CI 29.9%-33.5%), and a NPV of 99.9% (95% CI 99.3%-100%) for major injury and a sensitivity of 90.7%(95% CI 88.3%-92.8%), a specificity of 37.9% (95% CI 35.8%-40.1%), and a NPV of 91.8%(95% CI 89.7%-93.6%) for either major or minor injury. Regarding the limitations of our work, some clinicians may disagree with our injury classification and sensitivity thresholds for injury detection. Conclusions We prospectively derived and validated two DIs (Chest CT-All and Chest CT-Major) that identify blunt trauma patients with clinically significant thoracic injuries with high sensitivity, allowing for a safe reduction of approximately 25%-37% of unnecessary chest CTs. Trauma evaluation protocols that incorporate these DIs may decrease unnecessary costs and radiation exposure in the disproportionately young trauma population. C1 [Rodriguez, Robert M.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Langdorf, Mark I.] Univ Calif Irvine, Dept Emergency Med, Irvine, CA USA. [Nishijima, Daniel] Univ Calif Davis, Dept Emergency Med, Davis, CA 95616 USA. [Baumann, Brigitte M.] Rowan Univ, Cooper Med Sch, Dept Emergency Med, Camden, NJ USA. [Hendey, Gregory W.] UCSF Fresno Med Educ & Res, Dept Emergency Med, Fresno, CA USA. [Medak, Anthony J.] Univ Calif San Diego, Sch Med, Dept Emergency Med, San Diego, CA 92103 USA. [Raja, Ali S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Allen, Isabel E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mower, William R.] Univ Calif Los Angeles, Dept Emergency Med, Los Angeles, CA USA. RP Rodriguez, RM (reprint author), Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. EM robert.rodriguez@emergency.ucsf.edu OI Hendey, Gregory/0000-0002-0170-8743 FU University of California Center for Health Quality and Innovation (CHQI) [071:2011] FX Funded by University of California Center for Health Quality and Innovation (CHQI): 071:2011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 5 Z9 5 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD OCT PY 2015 VL 12 IS 10 AR e1001883 DI 10.1371/journal.pmed.1001883 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA CV7PN UT WOS:000364466600001 PM 26440607 ER PT J AU Taylor, AB Pica-Mattoccia, L Polcaro, CM Donati, E Cao, XH Basso, A Guidi, A Rugel, AR Holloway, SP Anderson, TJC Hart, PJ Cioli, D LoVerde, PT AF Taylor, Alexander B. Pica-Mattoccia, Livia Polcaro, Chiara M. Donati, Enrica Cao, Xiaohang Basso, Annalisa Guidi, Alessandra Rugel, Anastasia R. Holloway, Stephen P. Anderson, Timothy J. C. Hart, P. John Cioli, Donato LoVerde, Philip T. TI Structural and Functional Characterization of the Enantiomers of the Antischistosomal Drug Oxamniquine SO PLoS Neglected Tropical Diseases LA English DT Article ID IN-VITRO METABOLISM; LIQUID-CHROMATOGRAPHY; SCHISTOSOMA-MANSONI; RESOLUTION AB Background For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a similar to 30 kDa S. mansoni sulfotransferase (SmSULT) was identified as the target of OXA action. Methodology/Principal Findings Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, while R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA center dot SmSULT and S-OXA center dot SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA. Conclusions/Significance Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. These findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds. C1 [Taylor, Alexander B.; Cao, Xiaohang; Rugel, Anastasia R.; Holloway, Stephen P.; Hart, P. John; LoVerde, Philip T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. [Pica-Mattoccia, Livia; Basso, Annalisa; Guidi, Alessandra; Cioli, Donato] CNR, Inst Cell Biol & Neurobiol, Rome, Italy. [Polcaro, Chiara M.; Donati, Enrica] CNR, Inst Chem Methodol, Rome, Italy. [Basso, Annalisa] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Anderson, Timothy J. C.] Texas Biomed Res Inst, San Antonio, TX USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Taylor, AB (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM pjh@biochem.uthscsa.edu; dcioli@ibc.cnr.it; loverde@uthscsa.edu FU NIH [1R01AI115691]; WHO [HQNTD1206356]; UTHSCSA Presidents Collaborative Research Fund; Robert A. Welch Foundation [AQ-1399]; National Institute of General Medical Sciences from the National Institutes of Health [P41 GM103403]; NIH-ORIP HEI grant [S10 RR029205]; Argonne National Laboratory [DE-AC02-06CH11357]; National Center for Advancing Translational Sciences, National Institutes of Health [TL1 TR001119] FX This research was supported by NIH grant 1R01AI115691 (PTL and PJH), WHO grant HQNTD1206356 (PTL), the UTHSCSA Presidents Collaborative Research Fund (PTL and PJH), and the Robert A. Welch Foundation (AQ-1399, PJH) Support for the X-ray Crystallography Core Laboratory by the UTHSCSA Office of the Vice President for Research is gratefully acknowledged. This work is based upon research conducted at the Northeastern Collaborative Access Team beamlines, which are funded by the National Institute of General Medical Sciences from the National Institutes of Health (P41 GM103403). The Pilatus 6M detector on 24-ID-C beam line is funded by a NIH-ORIP HEI grant (S10 RR029205). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. ARR was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant TL1 TR001119. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 20 TC 1 Z9 1 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD OCT PY 2015 VL 9 IS 10 AR e0004132 DI 10.1371/journal.pntd.0004132 PG 13 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CV7NC UT WOS:000364459600037 PM 26485649 ER PT J AU Gupta, PK Godec, J Wolski, D Adland, E Yates, K Pauken, KE Cosgrove, C Ledderose, C Junger, WG Robson, SC Wherry, EJ Alter, G Goulder, PJR Klenerman, P Sharpe, AH Lauer, GM Haining, WN AF Gupta, Prakash K. Godec, Jernej Wolski, David Adland, Emily Yates, Kathleen Pauken, Kristen E. Cosgrove, Cormac Ledderose, Carola Junger, Wolfgang G. Robson, Simon C. Wherry, E. John Alter, Galit Goulder, Philip J. R. Klenerman, Paul Sharpe, Arlene H. Lauer, Georg M. Haining, W. Nicholas TI CD39 Expression Identifies Terminally Exhausted CD8(+) T Cells SO PLoS Pathogens LA English DT Article ID CHRONIC VIRAL-INFECTION; ADENOSINE-MEDIATED INHIBITION; HEPATITIS-C VIRUS; ATP-DIPHOSPHOHYDROLASE; IMMUNE SUPPRESSION; EFFECTOR FUNCTION; PD-1 EXPRESSION; ACTIVATION; PERSISTENCE; RECEPTORS AB Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8(+) T cells. CD8(+) T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8(+) T cells in chronic infection is enzymatically active, co- expressed with PD- 1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus- specific CD8(+) T cells contain a population of CD39high CD8(+) T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8(+) T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion. C1 [Gupta, Prakash K.; Godec, Jernej; Yates, Kathleen; Haining, W. Nicholas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Gupta, Prakash K.; Adland, Emily; Goulder, Philip J. R.; Klenerman, Paul] Univ Oxford, Oxford, England. [Godec, Jernej; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Godec, Jernej; Sharpe, Arlene H.] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA USA. [Godec, Jernej; Sharpe, Arlene H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wolski, David; Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Wolski, David; Lauer, Georg M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Pauken, Kristen E.; Wherry, E. John] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Pauken, Kristen E.; Wherry, E. John] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cosgrove, Cormac; Alter, Galit] Ragon Inst Massachusetts Gen Hosp Harvard Univ &, Cambridge, MA USA. [Cosgrove, Cormac; Ledderose, Carola] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA. [Robson, Simon C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Div Gastroenterol, Boston, MA 02215 USA. [Sharpe, Arlene H.; Haining, W. Nicholas] Broad Inst MIT & Harvard, Cambridge, MA USA. [Haining, W. Nicholas] Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Haining, WN (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM Nicholas_Haining@dfci.harvard.edu FU NIAID NIH HHS [U19 AI082630]; Wellcome Trust [091663, 104748] NR 56 TC 15 Z9 16 U1 2 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2015 VL 11 IS 10 AR e1005177 DI 10.1371/journal.ppat.1005177 PG 21 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CV7OE UT WOS:000364462700020 PM 26485519 ER PT J AU Lu, R Herrera, BB Eshleman, HD Fu, Y Bloom, A Li, ZG Sacks, DB Goldberg, MB AF Lu, Richard Herrera, Bobby Brooke Eshleman, Heather D. Fu, Yang Bloom, Alexander Li, Zhigang Sacks, David B. Goldberg, Marcia B. TI Shigella Effector OspB Activates mTORC1 in a Manner That Depends on IQGAP1 and Promotes Cell Proliferation SO PLOS PATHOGENS LA English DT Article ID FLEXNERI; PATHWAY; DEATH; PROTEIN; PHOSPHORYLATION; INFLAMMASOME; INACTIVATION; PATHOGENESIS; CYTOSKELETON; EXPRESSION AB The intracellular bacterial pathogen Shigella infects and spreads through the human intestinal epithelium. Effector proteins delivered by Shigella into cells promote infection by modulating diverse host functions. We demonstrate that the effector protein OspB interacts directly with the scaffolding protein IQGAP1, and that the absence of either OspB or IQGAP1 during infection leads to larger areas of S. flexneri spread through cell monolayers. We show that the effect on the area of bacterial spread is due to OspB triggering increased cell proliferation at the periphery of infected foci, thereby replacing some of the cells that die within infected foci and restricting the area of bacterial spread. We demonstrate that OspB enhancement of cell proliferation results from activation of mTORC1, a master regulator of cell growth, and is blocked by the mTORC1-specific inhibitor rapamycin. OspB activation of mTORC1, and its effects on cell proliferation and bacterial spread, depends on IQGAP1. Our results identify OspB as a regulator of mTORC1 and mTORC1-dependent cell proliferation early during S. flexneri infection and establish a role for IQGAP1 in mTORC1 signaling. They also raise the possibility that IQGAP1 serves as a scaffold for the assembly of an OspB-mTORC1 signaling complex. C1 [Lu, Richard; Herrera, Bobby Brooke; Eshleman, Heather D.; Fu, Yang; Bloom, Alexander; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02142 USA. [Lu, Richard; Eshleman, Heather D.; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Li, Zhigang; Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02142 USA. EM marcia.goldberg@mgh.harvard.edu FU NIH [F32AI073035, R01AI081724]; New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease [U54AI057159]; ICCB-Longwood facility (Harvard Medical School) FX This work was supported by NIH F32AI073035 (to RL) and NIH R01AI081724 (to MBG) and by the Intramural Research Program of the NIH (to DBS). The human genome RNAi was made available through the support of the New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease (U54AI057159) and the ICCB-Longwood facility (Harvard Medical School). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 2 Z9 2 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2015 VL 11 IS 10 AR e1005200 DI 10.1371/journal.ppat.1005200 PG 21 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CV7OE UT WOS:000364462700034 PM 26473364 ER PT J AU Agboola, F Bernard, D Savoia, E Biddinger, PD AF Agboola, Foluso Bernard, Dorothy Savoia, Elena Biddinger, Paul D. TI Development of an Online Toolkit for Measuring Performance in Health Emergency Response Exercises SO PREHOSPITAL AND DISASTER MEDICINE LA English DT Article DE disaster planning; emergency preparedness exercise; exercise evaluation; measures; performance improvement ID PREPAREDNESS AB Introduction: Exercises that simulate emergency scenarios are accepted widely as an essential component of a robust Emergency Preparedness program. Unfortunately, the variability in the quality of the exercises conducted, and the lack of standardized processes to measure performance, has limited the value of exercises in measuring preparedness. Methods: In order to help health organizations improve the quality and standardization of the performance data they collect during simulated emergencies, a model online exercise evaluation toolkit was developed using performance measures tested in over 60 Emergency Preparedness exercises. The exercise evaluation toolkit contains three major components: (1) a database of measures that can be used to assess performance during an emergency response exercise; (2) a standardized data collection tool (form); and (3) a program that populates the data collection tool with the measures that have been selected by the user from the database. The evaluation toolkit was pilot tested from January through September 2014 in collaboration with 14 partnering organizations representing 10 public health agencies and four health care agencies from eight states across the US. Exercise planners from the partnering organizations were asked to use the toolkit for their exercise evaluation process and were interviewed to provide feedback on the use of the toolkit, the generated evaluation tool, and the usefulness of the data being gathered for the development of the exercise after-action report. Results: Ninety-three percent (93%) of exercise planners reported that they found the online database of performance measures appropriate for the creation of exercise evaluation forms, and they stated that they would use it again for future exercises. Seventy-two percent (72%) liked the exercise evaluation form that was generated from the toolkit, and 93% reported that the data collected by the use of the evaluation form were useful in gauging their organization's performance during the exercise. Seventy-nine percent (79%) of exercise planners preferred the evaluation form generated by the toolkit to other forms of evaluations. Conclusion: Results of this project show that users found the newly developed toolkit to be user friendly and more relevant to measurement of specific public health and health care capabilities than other tools currently available. The developed toolkit may contribute to the further advancement of developing a valid approach to exercise performance measurement. C1 [Agboola, Foluso; Bernard, Dorothy; Savoia, Elena; Biddinger, Paul D.] Harvard Univ, TH Chan Sch Publ Hlth, Div Policy Translat & Leadership Dev, Boston, MA 02115 USA. [Savoia, Elena] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Biddinger, Paul D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Agboola, F (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Div Policy Translat & Leadership Dev, 401 Pk Dr, Boston, MA 02115 USA. EM fagboola@hsph.harvard.edu FU OPHPR CDC HHS [5P01TP000307-05, 1U90TP000417-05] NR 14 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1049-023X EI 1945-1938 J9 PREHOSPITAL DISASTER JI Prehospital Disaster Med. PD OCT PY 2015 VL 30 IS 5 BP 503 EP 508 DI 10.1017/S1049023X15005117 PG 6 WC Emergency Medicine SC Emergency Medicine GA CW0WB UT WOS:000364709500014 PM 26369757 ER PT J AU Bruno, MA Walker, EA Abujudeh, HH AF Bruno, Michael A. Walker, Eric A. Abujudeh, Hani H. TI Understanding and Confronting Our Mistakes: The Epidemiology of Error in Radiology and Strategies for Error Reduction SO RADIOGRAPHICS LA English DT Article ID DIAGNOSTIC ERROR; PERCEPTION; RESPECT; CANCER AB Arriving at a medical diagnosis is a highly complex process that is extremely error prone. Missed or delayed diagnoses often lead to patient harm and missed opportunities for treatment. Since medical imaging is a major contributor to the overall diagnostic process, it is also a major potential source of diagnostic error. Although some diagnoses may be missed because of the technical or physical limitations of the imaging modality, including image resolution, intrinsic or extrinsic contrast, and signal-to-noise ratio, most missed radiologic diagnoses are attributable to image interpretation errors by radiologists. Radiologic interpretation cannot be mechanized or automated; it is a human enterprise based on complex psychophysiologic and cognitive processes and is itself subject to a wide variety of error types, including perceptual errors (those in which an important abnormality is simply not seen on the images) and cognitive errors (those in which the abnormality is visually detected but the meaning or importance of the finding is not correctly understood or appreciated). The overall prevalence of radiologists' errors in practice does not appear to have changed since it was first estimated in the 1960s. The authors review the epidemiology of errors in diagnostic radiology, including a recently proposed taxonomy of radiologists' errors, as well as research findings, in an attempt to elucidate possible underlying causes of these errors. The authors also propose strategies for error reduction in radiology. On the basis of current understanding, specific suggestions are offered as to how radiologists can improve their performance in practice. (C) RSNA, 2015. C1 [Bruno, Michael A.; Walker, Eric A.] Penn State Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA. [Walker, Eric A.] Uniformed Serv Univ Hlth Sci, Dept Radiol & Nucl Med, Bethesda, MD 20814 USA. [Abujudeh, Hani H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Bruno, MA (reprint author), Penn State Milton S Hershey Med Ctr, Dept Radiol, H-066,500 Univ Dr, Hershey, PA 17033 USA. EM mbruno@psu.edu NR 33 TC 4 Z9 4 U1 1 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2015 VL 35 IS 6 BP 1668 EP 1676 DI 10.1148/rg.2015150023 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6DV UT WOS:000364361800006 PM 26466178 ER PT J AU Kalra, MK Sodickson, AD Mayo-Smith, WW AF Kalra, Mannudeep K. Sodickson, Aaron D. Mayo-Smith, William W. TI CT Radiation: Key Concepts for Gentle and Wise Use SO RADIOGRAPHICS LA English DT Article ID TUBE CURRENT MODULATION; DOSE INDEX REGISTRY; COMPUTED-TOMOGRAPHY; ITERATIVE RECONSTRUCTION; IONIZING-RADIATION; PEDIATRIC CT; IMAGE-RECONSTRUCTION; SUBSEQUENT RISK; CANCER-RISK; REDUCTION AB Use of computed tomography (CT) in medicine comes with the responsibility of its appropriate (wise) and safe (gentle) application to obtain required diagnostic information with the lowest possible dose of radiation. CT provides useful information that may not be available with other imaging modalities in many clinical situations in children and adults. Inappropriate or excessive use of CT should be avoided, especially if required information can be obtained in an accurate and time-efficient manner with other modalities that require a lower radiation dose, or non-radiation-based imaging modalities such as ultrasonography and magnetic resonance imaging. In addition to appropriate use of CT, the radiology community also must monitor scanning practices and protocols. When appropriate, high-contrast regions and lesions should be scanned with reduced dose, but overly zealous dose reduction should be avoided for assessment of low-contrast lesions. Patients' cross-sectional body size should be taken into account to deliver lower radiation dose to smaller patients and children. Wise use of CT scanning with gentle application of radiation dose can help maximize the diagnostic value of CT, as well as address concerns about potential risks of radiation. In this article, key concepts in CT radiation dose are reviewed, including CT dose descriptors; radiation doses from CT procedures; and factors and technologies that affect radiation dose and image quality, including their use in creating dose-saving protocols. Also discussed are the contributions of radiation awareness campaigns such as the Image Gently and Image Wisely campaigns and the American College of Radiology Dose Index Registry initiatives. (C) RSNA, 2015. C1 [Kalra, Mannudeep K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kalra, Mannudeep K.; Sodickson, Aaron D.; Mayo-Smith, William W.] Harvard Univ, Sch Med, Boston, MA USA. [Sodickson, Aaron D.; Mayo-Smith, William W.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Mayo-Smith, WW (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM wmayo-smith@partners.org NR 73 TC 6 Z9 7 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2015 VL 35 IS 6 BP 1706 EP 1721 DI 10.1148/rg.2015150118 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6DV UT WOS:000364361800009 PM 26466180 ER PT J AU Anvari, A Halpern, EF Samir, AE AF Anvari, Arash Halpern, Elkan F. Samir, Anthony E. TI Statistics 101 for Radiologists SO RADIOGRAPHICS LA English DT Article ID CLINICAL-RESEARCH; CONTINUOUS-VARIABLES; FUNDAMENTALS; PROPORTIONS; REGRESSION; AGREEMENT; INFERENCE; SAMPLE AB Diagnostic tests have wide clinical applications, including screening, diagnosis, measuring treatment effect, and determining prognosis. Interpreting diagnostic test results requires an understanding of key statistical concepts used to evaluate test efficacy. This review explains descriptive statistics and discusses probability, including mutually exclusive and independent events and conditional probability. In the inferential statistics section, a statistical perspective on study design is provided, together with an explanation of how to select appropriate statistical tests. Key concepts in recruiting study samples are discussed, including representativeness and random sampling. Variable types are defined, including predictor, outcome, and covariate variables, and the relationship of these variables to one another. In the hypothesis testing section, we explain how to determine if observed differences between groups are likely to be due to chance. We explain type I and II errors, statistical significance, and study power, followed by an explanation of effect sizes and how confidence intervals can be used to generalize observed effect sizes to the larger population. Statistical tests are explained in four categories: t tests and analysis of variance, proportion analysis tests, nonparametric tests, and regression techniques. We discuss sensitivity, specificity, accuracy, receiver operating characteristic analysis, and likelihood ratios. Measures of reliability and agreement, including kappa statistics, intraclass correlation coefficients, and Bland-Altman graphs and analysis, are introduced. (C) RSNA, 2015. C1 [Anvari, Arash; Halpern, Elkan F.; Samir, Anthony E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Ultrasound Div, Boston, MA 02114 USA. RP Anvari, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Ultrasound Div, 55 Fruit St,White 270, Boston, MA 02114 USA. EM Anvari.arash@mgh.harvard.edu RI Anvari, Arash/B-4329-2014 OI Anvari, Arash/0000-0001-5887-581X NR 31 TC 3 Z9 3 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2015 VL 35 IS 6 BP 1789 EP 1801 DI 10.1148/rg.2015150112 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6DV UT WOS:000364361800015 PM 26466186 ER PT J AU Sibila, O Suarez-Cuartin, G Rodrigo-Troyano, A Fardon, TC Finch, S Mateus, EF Garcia-Bellmunt, L Castillo, D Vidal, S Sanchez-Reus, F Restrepo, MI Chalmers, JD AF Sibila, Oriol Suarez-Cuartin, Guillermo Rodrigo-Troyano, Ana Fardon, Thomas C. Finch, Simon Mateus, Eder Freddy Garcia-Bellmunt, Laia Castillo, Diego Vidal, Silvia Sanchez-Reus, Ferran Restrepo, Marcos I. Chalmers, James D. TI Secreted mucins and airway bacterial colonization in non-CF bronchiectasis SO RESPIROLOGY LA English DT Article DE bronchiectasis; bronchial colonization; lung defense mechanism; mucin ID CYSTIC FIBROSIS BRONCHIECTASIS; CELLS IN-VITRO; EPITHELIAL-CELLS; MUC5B MUCINS; LONG-TERM; DISEASE; MUCUS; INFLAMMATION; MECHANISMS; SPUTUM AB Background and objective: Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non-cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms (PPM) in the airways of stable bronchiectasis patients. Methods: Clinically stable bronchiectasis patients were studied prospectively at two centres. Patients with other pulmonary conditions were excluded. Spontaneous sputum was subject to bacterial culture, and secreted mucins (MUC2, MUC5AC and MUC5B) were measured in sputum supernatants by ELISA. Results: A total of 50 patients were included. PPM were identified from sputum samples in 30 (60%), with Pseudomonas aeruginosa (n = 10) and Haemophilus influenzae (n = 10) as the most common PPM. There were no baseline differences among airway colonized and non-colonized patients. Patients with airways colonized by PPM presented higher levels of airway MUC2. No differences in MUC5AC levels were found among groups, whereas MUC5B levels were undetectable. Patients with P. aeruginosa colonization expressed the highest levels of MUC2. High levels of MUC2 and MUC5AC are also correlated with disease severity using the Bronchiectasis Severity Index. Conclusions: Airway MUC2 levels were higher in bronchiectasis patients colonized with PPM compared with those without airway colonization, especially in patients with P. aeruginosa. These findings suggest that airway-secreted mucins levels may play a role in the pathogenesis of airway infection in non-CF bronchiectasis. C1 [Sibila, Oriol; Suarez-Cuartin, Guillermo; Rodrigo-Troyano, Ana; Garcia-Bellmunt, Laia; Castillo, Diego] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Resp Dept, E-08193 Barcelona, Spain. [Sibila, Oriol; Suarez-Cuartin, Guillermo; Rodrigo-Troyano, Ana; Mateus, Eder Freddy; Garcia-Bellmunt, Laia; Castillo, Diego; Vidal, Silvia; Sanchez-Reus, Ferran] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau IIB St Pau, E-08193 Barcelona, Spain. [Mateus, Eder Freddy; Vidal, Silvia] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Expt Immunol Lab, E-08193 Barcelona, Spain. [Sanchez-Reus, Ferran] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Microbiol, E-08193 Barcelona, Spain. [Fardon, Thomas C.; Finch, Simon; Chalmers, James D.] Univ Dundee, Tayside Resp Res Grp, Dundee, Scotland. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Crit Care Dept, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Med, San Antonio, TX 78229 USA. RP Sibila, O (reprint author), Hosp Santa Creu & Sant Pau, Resp Dept, St Antoni M Claret St 167, Barcelona 08025, Spain. EM osibila@santpau.cat OI Castillo, Diego/0000-0002-4862-3595 FU Sociedad Espanola de Neumologia (SEPAR); Fundacio Catalana de Pneumologia (FUCAP); Tenovus Scotland; National Heart, Lung, and Blood Institute [K23HL096054] FX The project described was supported by Sociedad Espanola de Neumologia (SEPAR), Fundacio Catalana de Pneumologia (FUCAP) and Tenovus Scotland. Dr Restrepo's time is partially protected by Award Number K23HL096054 from the National Heart, Lung, and Blood Institute. NR 33 TC 4 Z9 4 U1 1 U2 4 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 OCT PY 2015 VL 20 IS 7 BP 1082 EP 1088 DI 10.1111/resp.12595 PG 7 WC Respiratory System SC Respiratory System GA CV9GD UT WOS:000364594700012 PM 26172851 ER PT J AU Fava, M AF Fava, Maurizio TI The role of regulators, investigators, and patient participants in the rise of the placebo response in major depressive disorder SO WORLD PSYCHIATRY LA English DT Editorial Material ID US FOOD; CLINICAL-TRIALS; PERSPECTIVE C1 [Fava, Maurizio] Massachusetts Gen Hosp, CTNI, Boston, MA 02114 USA. [Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, CTNI, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1723-8617 EI 2051-5545 J9 WORLD PSYCHIATRY JI World Psychiatry PD OCT PY 2015 VL 14 IS 3 BP 307 EP 308 DI 10.1002/wps.20247 PG 3 WC Psychiatry SC Psychiatry GA CV9HA UT WOS:000364597100016 PM 26407784 ER PT J AU Sarris, J Logan, AC Akbaraly, TN Amminger, GP Balanza-Martinez, V Freeman, MP Hibbeln, J Matsuoka, Y Mischoulon, D Mizoue, T Nanri, A Nishi, D Parletta, N Ramsey, D Rucklidge, JJ Sanchez-Villegas, A Scholey, A Su, KP Jacka, FN AF Sarris, Jerome Logan, Alan C. Akbaraly, Tasnime N. Amminger, G. Paul Balanza-Martinez, Vicent Freeman, Marlene P. Hibbeln, Joseph Matsuoka, Yutaka Mischoulon, David Mizoue, Tetsuya Nanri, Akiko Nishi, Daisuke Parletta, Natalie Ramsey, Drew Rucklidge, Julia J. Sanchez-Villegas, Almudena Scholey, Andrew Su, Kuan-Pin Jacka, Felice N. TI International Society for Nutritional Psychiatry Research consensus position statement: nutritional medicine in modern psychiatry SO WORLD PSYCHIATRY LA English DT Letter ID DIETARY PATTERN; MENTAL-HEALTH; ASSOCIATION; DEPRESSION; SYMPTOMS; COHORT; AGE C1 [Sarris, Jerome] Univ Melbourne, Dept Psychiat, Melbourne, Vic, Australia. [Sarris, Jerome; Scholey, Andrew] Swinburne Univ Technol, Ctr Human Psychopharmacol, Hawthorn, Vic 3122, Australia. [Logan, Alan C.] CAMNR, Calabasas, CA USA. [Akbaraly, Tasnime N.] INSERM, U1198, Montpellier, France. [Akbaraly, Tasnime N.] EPHE, F-75006 Paris, France. [Akbaraly, Tasnime N.] Univ Montpellier 2, Montpellier, France. [Akbaraly, Tasnime N.] UCL, Dept Epidemiol & Publ Hlth, London, England. [Amminger, G. Paul] Natl Ctr Excellence Youth Mental Hlth, Orygen, Parkville, Vic, Australia. [Balanza-Martinez, Vicent] Hosp La Fe, Teaching Unit Psychiat & Psychol Med, E-46009 Valencia, Spain. [Balanza-Martinez, Vicent] Univ Valencia, Sch Med, Polytech Hosp, CIBERSAM, Valencia, Spain. [Freeman, Marlene P.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat, Boston, MA 02114 USA. [Hibbeln, Joseph] NIAAA, NIH, Bethesda, MD USA. [Matsuoka, Yutaka] Natl Ctr Neurol & Psychiat, Translat Med Ctr, Dept Clin Epidemiol, Tokyo, Japan. [Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Mizoue, Tetsuya; Nanri, Akiko] Natl Ctr Global Hlth & Med, Dept Epidemiol & Prevent, Tokyo, Japan. [Parletta, Natalie] Univ S Australia, Sch Populat Hlth, Adelaide, SA 5001, Australia. [Ramsey, Drew] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Rucklidge, Julia J.] Univ Canterbury, Dept Psychol, Christchurch 1, New Zealand. [Sanchez-Villegas, Almudena] Univ Palmas Gran Canaria, Res Inst Biomed & Hlth Sci, Las Palmas Gran Canaria, Spain. [Sanchez-Villegas, Almudena] Inst Salud Carlos III, CIBEROBN, Madrid, Spain. [Su, Kuan-Pin] China Med Univ Hosp, Dept Psychiat, Taichung, Taiwan. [Su, Kuan-Pin] China Med Univ Hosp, Mind Body Interface Lab, Taichung, Taiwan. [Su, Kuan-Pin] China Med Univ, Grad Inst Neural & Cognit Sci, Taichung, Taiwan. [Jacka, Felice N.] Deakin Univ, Sch Med, IMPACT SRC, Geelong, Vic 3220, Australia. [Jacka, Felice N.] Murdoch Childrens Res Ctr, Parkville, Vic, Australia. [Jacka, Felice N.] Univ Melbourne, Royal Melbourne Hosp, Dept Psychiat, Melbourne, Vic 3050, Australia. [Jacka, Felice N.] Black Dog Inst, Randwick, NSW, Australia. RP Sarris, J (reprint author), Univ Melbourne, Dept Psychiat, Melbourne, Vic, Australia. NR 9 TC 6 Z9 6 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1723-8617 EI 2051-5545 J9 WORLD PSYCHIATRY JI World Psychiatry PD OCT PY 2015 VL 14 IS 3 BP 370 EP 371 DI 10.1002/wps.20223 PG 2 WC Psychiatry SC Psychiatry GA CV9HA UT WOS:000364597100031 PM 26407799 ER PT J AU Trifanov, DS Dhyani, M Bledsoe, JR Misdraji, J Bhan, AK Chung, RT Samir, A AF Trifanov, Dmitry S. Dhyani, Manish Bledsoe, Jacob R. Misdraji, Joseph Bhan, Atul K. Chung, Raymond T. Samir, Anthony E. TI Amyloidosis of the liver on shear wave elastography: case report and review of literature SO ABDOMINAL IMAGING LA English DT Review DE Amyloidosis; Elastography; Liver fibrosis; Liver biopsy; SWE; Ultrasound elastography ID CHRONIC HEPATITIS-C; TRANSIENT ELASTOGRAPHY; SYSTEMIC AMYLOIDOSIS; NATIONWIDE SURVEY; NATURAL-HISTORY; FIBROSIS; STIFFNESS; BIOPSY; CHOLESTASIS; DIAGNOSIS AB Amyloidosis is extremely rare, with an estimated 2225 new US cases reported annually. Signs and symptoms of the disease are subtle and imaging findings are not pathognomonic. Currently, diagnosis requires biopsy to demonstrate the deposition of amyloid. Elastography is a new imaging modality that evaluates tissue elasticity. It has shown to have efficacy in characterizing thyroid nodules, detecting prostate cancer, and staging liver fibrosis. We present a case of hepatic amyloidosis in a 51-year-old male that demonstrates significantly increased stiffness with a median value of 99.1 kPa (range 25.7-188.9 kPa) on shear-wave elastography (SWE) imaging, which is significantly higher than the cut-off range reported for cirrhosis on SWE (10.4-11.5 kPa). This finding raises the possibility that elastographic imaging may be sensitive to tissue mechanical changes induced by amyloid deposition. C1 [Trifanov, Dmitry S.; Dhyani, Manish; Samir, Anthony E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Bledsoe, Jacob R.; Misdraji, Joseph; Bhan, Atul K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hepatol Med, Boston, MA 02114 USA. RP Dhyani, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM dhyani.manish@mgh.harvard.edu OI Dhyani, Manish/0000-0002-2651-1859 NR 54 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 OCT PY 2015 VL 40 IS 8 BP 3078 EP 3083 DI 10.1007/s00261-015-0519-4 PG 6 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CV0PD UT WOS:000363952000015 PM 26254907 ER PT J AU Mao, Y Hedgire, S Prapruttam, D Harisinghani, M AF Mao, Yun Hedgire, Sandeep Prapruttam, Duangkamon Harisinghani, Mukesh TI Predictive models for lymph node metastases in patients with testicular germ cell tumors SO ABDOMINAL IMAGING LA English DT Article DE Testicular cancer; Lymph nodes; CT surveillance; Seminoma; Nonseminomatous germ cell tumors ID STAGE-I SEMINOMA; PROGNOSTIC-FACTORS; MULTIVARIATE-ANALYSIS; RISK-FACTORS; CANCER; SURVEILLANCE; RELAPSE; MULTICENTER; NONSEMINOMA; CARCINOMA AB Purpose: To develop predictive models for lymph node (LN) metastasis in testicular germ cell tumors. Materials and Methods: 291 patients with testicular germ cell tumors were included, which were divided into seminomatous and nonseminomatous groups. For screening the risk factors for LN metastasis, the tumor-related characteristics (including histopathological information and tumor markers) alpha fetoprotein and the lymph node-related features on CT were compared between metastatic cases and nonmetastatic cases. Two logistic regression models were built for each histological group, one depending on all tumor- and lymph node-related risk factors (Model 1) and another only on tumor-related factors (Model 2). Receivers operating characteristic curves were used to evaluate the predictive abilities of these models. Results: 117 positive nodes/regions were identified in 68 patients, including 51 metastases and 17 occult metastases. Based on the selected independent risk factors, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of Models 1 and 2 in seminomatous and nonseminomatous groups were (95.5%, 95.3%, 95.3%, 77.8%, and 99.2%), (63.6%, 83.6%, 80.7%, 40.0%, and 93.0%), (93.5%, 94.7%, 94.3%, 89.6%, and 96.8%), and (89.1%, 44.2%, 58.9%, 43.6%, and 89.4%), respectively. Conclusion: Two predictive models for each seminomatous and nonseminomatous testicular tumor were established based on lymph node- and tumor-related risk factors. In patients with tumor and lymph node-related risk factors, regular CT surveillance is likely sufficient for predicting LN status, while in the patients without any tumor and lymph node-related risk factors a long interval-time CT follow-up should be considered. Additionally, right side tumors tend to involve contralateral LNs compared to left side ones. Positive inguinal LNs more frequently occur in patients with a history of groin surgery. C1 [Mao, Yun] Chongqing Med Univ, Affiliated Hosp 1, Dept Radiol, Chongqing 400016, Peoples R China. [Hedgire, Sandeep; Prapruttam, Duangkamon; Harisinghani, Mukesh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Hedgire, S (reprint author), Chongqing Med Univ, Affiliated Hosp 1, Dept Radiol, 1 Youyi St, Chongqing 400016, Peoples R China. EM maoyun1979@163.com; hedgire.sandeep@mgh.harvard.edu; duangkamon.prr@mahidol.ac.th; mharisinghani@mgh.harvard.edu NR 28 TC 0 Z9 0 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 OCT PY 2015 VL 40 IS 8 BP 3196 EP 3205 DI 10.1007/s00261-015-0526-5 PG 10 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CV0PD UT WOS:000363952000031 PM 26288987 ER PT J AU Karaosmanoglu, AD Onur, MR Saini, S Taberi, A Karcaaltincaba, M AF Karaosmanoglu, Ali Devrim Onur, Mehmet Ruhi Saini, Sanjay Taberi, Azadeh Karcaaltincaba, Musturay TI Imaging of hepatobiliary involvement in sarcoidosis SO ABDOMINAL IMAGING LA English DT Article DE Sarcoidosis; Liver; Ultrasonography; Computed tomography; Magnetic resonance imaging ID PRIMARY SCLEROSING CHOLANGITIS; OF-THE-LITERATURE; BILIARY-TRACT OBSTRUCTION; HEPATIC SARCOIDOSIS; LIVER-TRANSPLANTATION; NODULAR SARCOIDOSIS; SPLENIC SARCOIDOSIS; CIRRHOSIS; MANIFESTATIONS; PATHOGENESIS AB Sarcoidosis is mainly a disease of the respiratory system; however, several other organ systems may be affected in the course of the disease. Liver is one of the most frequently affected organs in the setting of sarcoidosis after lungs and lymph nodes. Microscopic hepatic involvement is common in these patients but is mostly clinically silent. However, in a significant portion of these patients, macroscopic findings can be detected in the course of the disease, and these findings may easily be confused with other benign and malignant conditions of the liver. The purposes of this article are to briefly summarize the clinical findings and the underlying pathophysiology of sarcoidosis and detailed presentation of the radiologic findings of hepatic involvement in this disease. We subgrouped the imaging findings based on the location and the radiologic appearance of the hepatic involvement. We tried to provide images that would enable the readers to link the imaging findings with the underlying pathology and clinical symptoms. C1 [Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Karcaaltincaba, Musturay] Hacettepe Univ, Sch Med, Dept Radiol, TR-06100 Ankara, Turkey. [Saini, Sanjay; Taberi, Azadeh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Onur, MR (reprint author), Hacettepe Univ, Sch Med, Dept Radiol, TR-06100 Ankara, Turkey. EM ruhionur@yahoo.com RI Karcaaltincaba, Musturay/A-3866-2016 OI Karcaaltincaba, Musturay/0000-0002-3384-0909 NR 43 TC 3 Z9 3 U1 0 U2 2 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 OCT PY 2015 VL 40 IS 8 BP 3330 EP 3337 DI 10.1007/s00261-015-0533-6 PG 8 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CV0PD UT WOS:000363952000044 PM 26318751 ER PT J AU Roussos, P Katsel, P Fam, P Tan, WL Purohit, DP Haroutunian, V AF Roussos, Panos Katsel, Pavel Fam, Peter Tan, Weilun Purohit, Dushyant P. Haroutunian, Vahram TI The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia SO ALZHEIMERS & DEMENTIA LA English DT Article DE Microglia; TYROBP; Mutation; Inflammation; Gene expression; Protein ID CUTTING EDGE; DISEASE; RESPONSES; MICROGLIA; SCHIZOPHRENIA; VARIANTS; IMMUNITY; REGISTRY; NODES; DAP12 AB Introduction: The objective of this study was to elucidate the relationship between the triggering receptor expressed on myeloid cells 2 (TREM2) risk variant, neuropathological lesions, alterations in gene and protein expression, and the severity of neuroinflammation. Methods: The genetic association study of the R47 H TREM2 variant with Alzheimer's disease (AD), neuropathology, and changes in TREM2 and TYRO protein tyrosine kinase-binding protein (TYROBP) gene and protein expression, and neuroinflammatory markers. Results: The TREM2 variant is associated with: (i) AD (odds ratio: 4.76; P = .014); (ii) increased density of amyloid plaques and neurofibrillary tangles in multiple brain regions; (iii) increased TREM2 (P = .041) and TYROBP (P = .006) gene expression; (iv) decreased TREM2 protein levels (P = .016); and (v) upregulation of proinflammatory cytokines (regulated on activation, normal T cell expressed and secreted [RANTES] and interferon [IFN] gamma) (P = .003) and nominal downregulation of protective markers (alpha 2-macroglobulin, interleukin 4 or IL-4, and ApoA1) (P = .018). Discussion: These findings link the TREM2 missense mutation with specific molecular abnormalities and increases in neuropathological lesions in the human brain. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Roussos, Panos; Katsel, Pavel; Tan, Weilun; Purohit, Dushyant P.; Haroutunian, Vahram] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Roussos, Panos] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Roussos, Panos] Icahn Sch Med Mt Sinai, Inst Multiscale Biol, New York, NY 10029 USA. [Roussos, Panos; Haroutunian, Vahram] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN 3, Bronx, NY USA. [Fam, Peter; Haroutunian, Vahram] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Purohit, Dushyant P.] Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA. RP Haroutunian, V (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM vahram.haroutunian@mssm.edu RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 FU National Institutes of Health [P01-AG02219, P50-AG05138, MH066392]; Veteran Administration MIRECC; Leir Foundation; Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai FX This work was supported by National Institutes of Health (P01-AG02219, P50-AG05138, MH066392 to VH), Veteran Administration MIRECC, Leir Foundation. This work was supported in part through the computational resources and staff expertise provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD OCT PY 2015 VL 11 IS 10 BP 1163 EP 1170 DI 10.1016/j.jalz.2014.10.013 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CV0UD UT WOS:000363968000005 PM 25499537 ER PT J AU Hyman, BT Growdon, JH Albers, MW Buckner, RL Chhatwal, J Gomez-Isla, MT Haass, C Hudry, E Jack, CR Johnson, KA Khachaturian, ZS Kim, DY Martin, JB Nitsch, RM Rosen, BR Selkoe, DJ Sperling, RA St George-Hyslop, P Tanzi, RE Yap, L Young, AB Phelps, CH McCaffrey, PG AF Hyman, Bradley T. Growdon, John H. Albers, Mark W. Buckner, Randy L. Chhatwal, Jasmeer Gomez-Isla, Maria Teresa Haass, Christian Hudry, Eloise Jack, Clifford R., Jr. Johnson, Keith A. Khachaturian, Zaven S. Kim, Doo Yeon Martin, Joseph B. Nitsch, Roger M. Rosen, Bruce R. Selkoe, Dennis J. Sperling, Reisa A. St George-Hyslop, Peter Tanzi, Rudolph E. Yap, Liang Young, Anne B. Phelps, Creighton H. McCaffrey, Patricia G. TI Massachusetts Alzheimer's Disease Research Center: Progress and challenges SO ALZHEIMERS & DEMENTIA LA English DT Article ID AMYLOID-BETA; PROTEIN; GENE C1 [Hyman, Bradley T.; Growdon, John H.; Albers, Mark W.; Chhatwal, Jasmeer; Gomez-Isla, Maria Teresa; Hudry, Eloise; Kim, Doo Yeon; Sperling, Reisa A.; Tanzi, Rudolph E.; Yap, Liang; Young, Anne B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hyman, Bradley T.; Growdon, John H.; Albers, Mark W.; Buckner, Randy L.; Chhatwal, Jasmeer; Gomez-Isla, Maria Teresa; Hudry, Eloise; Johnson, Keith A.; Kim, Doo Yeon; Rosen, Bruce R.; Selkoe, Dennis J.; Sperling, Reisa A.; Tanzi, Rudolph E.; Yap, Liang; Young, Anne B.] Harvard Univ, Sch Med, Boston, MA USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Haass, Christian] Univ Munich, Dept Biochem, Munich, Bavaria, Germany. [Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Johnson, Keith A.; Rosen, Bruce R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Johnson, Keith A.; Selkoe, Dennis J.; Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Khachaturian, Zaven S.] Khachaturian & Associates Inc, Potomac, MD USA. [Martin, Joseph B.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Nitsch, Roger M.] Univ Zurich, Dept Psychiat, Zurich, Switzerland. [St George-Hyslop, Peter] Univ Cambridge, Dept Clin Neurosci, Cambridge, England. [St George-Hyslop, Peter] Univ Toronto, Dept Med, Toronto, ON, Canada. [Phelps, Creighton H.] NIA, NIH, Bethesda, MD 20892 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM bhyman@mgh.harvard.edu RI Jack, Clifford/F-2508-2010 OI Jack, Clifford/0000-0001-7916-622X FU National Institute on Aging of the National Institutes of Health [P50 AG005134]; Biogen; Idec Lilly USA, LLC; FORUM Pharmaceuticals, Inc; Novartis; Pfizer, Inc.; Cure Alzheimer's Fund FX The Massachusetts Alzheimer's Disease Research Center (ADRC) is supported by the National Institute on Aging of the National Institutes of Health under award number P50 AG005134. The Center received support from the following companies for its 30th anniversary symposium: Biogen, Idec Lilly USA, LLC, FORUM Pharmaceuticals, Inc, Novartis, and Pfizer, Inc. The nonprofit Cure Alzheimer's Fund also provided funding support for the center's 30th anniversary celebrations. NR 17 TC 1 Z9 1 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD OCT PY 2015 VL 11 IS 10 BP 1241 EP 1245 DI 10.1016/j.jalz.2015.06.1887 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA CV0UD UT WOS:000363968000013 PM 26297855 ER PT J AU Ahmed, S Lewis, M Matuk, R Pisegna, J AF Ahmed, Shahzad Lewis, Micheal Matuk, Robin Pisegna, Joseph TI Heterotopic Salivary Gland Tissue in the Rectum of a Patient With Eosinophilic Colitis and Redundant Colon SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Ahmed, Shahzad] Cedars Sinai Med Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90048 USA. [Lewis, Micheal; Pisegna, Joseph] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Matuk, Robin] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 456 BP S196 EP S196 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715901006 ER PT J AU Al-Jiboury, H Wilgus, J Benhammou, J Patel, A Jacob, N Ohning, G Otomo-Corgel, J Pisegna, JR AF Al-Jiboury, Hala Wilgus, Jeremy Benhammou, Jihane Patel, Arpan Jacob, Noam Ohning, Gordon Otomo-Corgel, Joan Pisegna, Joseph R. TI The Gastric Refluxate in Patients With Gastroesophageal Reflux Disease (GERD) Has a Protective Effect on Periodontal Microbiota SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Al-Jiboury, Hala] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Wilgus, Jeremy; Jacob, Noam; Otomo-Corgel, Joan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Benhammou, Jihane] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Patel, Arpan; Ohning, Gordon] Univ Calif Los Angeles, Los Angeles, CA USA. [Pisegna, Joseph R.] Univ Calif Los Angeles, VA Greater Los Angeles Hlth System, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1723 BP S731 EP S731 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715903336 ER PT J AU Basu, PP Shah, NJ John, N Aloysius, M Brown, R AF Basu, P. Patrick Shah, Niraj James John, Nimy Aloysius, Mark Brown, Robert, Jr. TI Sofosbuvir and Ledipasvir in IBD Patients Treated With Advanced Biologics Including Ribavirin Eradicating Chronic Hepatitis C: Solataire C Trial: A Multicenter Clinical Prospective Pilot Study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Basu, P. Patrick] Columbia Univ, Sch Phys & Surg, Forest Hills, NY USA. [Shah, Niraj James] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, Yonkers, NY USA. [John, Nimy; Aloysius, Mark] Kings Cty Hosp Med Ctr, Forest Hills, NY USA. [Brown, Robert, Jr.] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 2204 BP S916 EP S916 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904362 ER PT J AU Basu, PP Shah, NJ John, N Aloysius, M Brown, R AF Basu, P. Patrick Shah, Niraj James John, Nimy Aloysius, Mark Brown, Robert, Jr. TI Sofosbuvir and Ledipasvir in Attainment of SVR12 in Sickle Cell Disease (SCD) Sub-population With Chronic Hepatitis C (CHC): A Single-Center, Prospective, Open-Label Clinical Pilot Stud: SLASH C Trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Basu, P. Patrick] Columbia Univ, Sch Phys & Surg, Forest Hills, NY USA. [Shah, Niraj James] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, Yonkers, NY USA. [John, Nimy; Aloysius, Mark] Kings Cty Hosp Med Ctr, Forest Hills, NY USA. [Brown, Robert, Jr.] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 2198 BP S914 EP S914 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904356 ER PT J AU Basu, PP Shah, NJ John, N Aloysius, M Brown, R AF Basu, P. Patrick Shah, Niraj James John, Nimy Aloysius, Mark Brown, Robert, Jr. TI Sofosbuvir and Ledipasvir Versus Sofosbuvir and Simeprevir Combination Therapy in the Management of Acute Hepatitis C: A Randomized Open Label Prospective Clinical Pilot Study. SLAM C Study, Interim Data SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Basu, P. Patrick] Columbia Univ, Sch Phys & Surg, Forest Hills, NY USA. [Shah, Niraj James] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, Yonkers, NY USA. [John, Nimy; Aloysius, Mark] Kings Cty Hosp Med Ctr, Forest Hills, NY USA. [Brown, Robert, Jr.] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 2192 BP S912 EP S912 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904350 ER PT J AU Benhammou, J Vu, J Parsons, W Luong, L Oh, S Lewis, M Beaven, S Germano, P Pisegna, JR AF Benhammou, Jihane Vu, John Parsons, Will Luong, Leon Oh, Suwan Lewis, Michael Beaven, Simon Germano, Patrizia Pisegna, Joseph R. TI Improvement in Hepatic Steatosis, Visceral Adiposity, and Appetite by High Dietary Protein Supplementation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Benhammou, Jihane] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Vu, John; Parsons, Will; Luong, Leon; Oh, Suwan; Lewis, Michael] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Beaven, Simon] Univ Calif Los Angeles, Los Angeles, CA USA. [Germano, Patrizia] VA Greater Los Angeles Hlth Syst, Los Angeles, CA USA. [Pisegna, Joseph R.] Univ Calif Los Angeles, VA Greater Los Angeles Hlth Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 2155 BP S897 EP S898 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904313 ER PT J AU Benhammou, J Al-Jiboury, H Jacob, N Ghassemi, K Sedarat, A Pisegna, J AF Benhammou, Jihane Al-Jiboury, Hala Jacob, Noam Ghassemi, Kevin Sedarat, Alireza Pisegna, Joseph TI EUS-Guided Fine Needle Aspiration (FNA) More Accurately Identifies Small Pancreatic Neuroendocrine Tumors (PNETs) Than CT-Guided FNA SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Benhammou, Jihane] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Al-Jiboury, Hala; Ghassemi, Kevin; Sedarat, Alireza] Univ Calif Los Angeles, Los Angeles, CA USA. [Jacob, Noam; Pisegna, Joseph] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 65 BP S27 EP S27 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715900066 ER PT J AU Churchill, C Okello, S Owori, R Nasasira, B Tumuhimbise, C Wang, AY Abonga, CL Mutiibwa, D Corey, K AF Churchill, Cristina Okello, Samson Owori, Rogers Nasasira, Benson Tumuhimbise, Christine Wang, Andrew Y. Abonga, Charles Lagoro Mutiibwa, David Corey, Kathleen TI Esophageal Squamous Cell Carcinoma in a Regional Referral Hospital in Southwest Uganda SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Churchill, Cristina] Univ Virginia, Dept Internal Med, Charlottesville, VA USA. [Okello, Samson; Nasasira, Benson; Tumuhimbise, Christine; Abonga, Charles Lagoro] Mbarara Univ Sci & Technol, Dept Internal Med, Mbarara, Uganda. [Okello, Samson] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Mbarara, Uganda. [Owori, Rogers] Gwatiro Hosp, Wakiso, Uganda. [Wang, Andrew Y.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Mutiibwa, David] Mbarara Univ Sci & Technol, Dept Surg, Mbarara, Uganda. [Corey, Kathleen] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Corey, Kathleen] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1674 BP S712 EP S712 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715903287 ER PT J AU Francis, F Kulich, SM Hashash, LG AF Francis, Fadi Kulich, Scott M. Hashash, Laws G. TI Diarrhea, Ascites, and Eosinophilia SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Francis, Fadi] Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Kulich, Scott M.; Hashash, Laws G.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1106 BP S481 EP S482 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715902205 ER PT J AU Garapati, K Camero, A Echavarria, J Malakouti, M Kundrotas, L AF Garapati, Karthik Camero, Alfredo Echavarria, Juan Malakouti, Mazyar Kundrotas, Leon TI Adherence to Surveillance Colonoscopy: An Investigation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Garapati, Karthik; Camero, Alfredo; Echavarria, Juan; Malakouti, Mazyar] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kundrotas, Leon] Audie L Murphy Vet Affairs Hosp, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 2286 BP S948 EP S948 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904445 ER PT J AU Goyal, D Kim, S Dutson, E Chen, YJ Pisegna, J Watson, RR AF Goyal, Deepinder Kim, Stephen Dutson, Erik Chen, Yijun Pisegna, Joseph Watson, Rabindra R. TI Endoscopic Trans-Oral Outlet Reduction in Combination with Gastroplasty (TORe-G) Is a Novel Technique That Is Highly Efficacious and Safe for Weight Loss in Patients With Failed Roux-en-Y Gastric Bypass (RYGB) SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Goyal, Deepinder] Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA USA. [Dutson, Erik; Chen, Yijun] Univ Calif Los Angeles, Los Angeles, CA USA. [Pisegna, Joseph] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Watson, Rabindra R.] Univ Calif Los Angeles, Intervent Endoscopy Serv, Los Angeles, CA USA. [Watson, Rabindra R.] Ctr Obes & Metab Hlth, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1521 BP S656 EP S657 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715903134 ER PT J AU Hashash, JG Bista, R Staton, KD Hartman, DJ Regueiro, M Binion, DG Francis, F Alnabhan, S Baidoo, L Swoger, J Brand, R Liu, Y AF Hashash, Jana G. Bista, Rajan Staton, Kevin D. Hartman, Douglas J. Regueiro, Miguel Binion, David G. Francis, Fadi Alnabhan, Samer Baidoo, Leonard Swoger, Jason Brand, Randall Liu, Yang TI Identifying Colonic Dysplasia and Cancer From Rectal Nuclear Nano-morphology Markers in Ulcerative Colitis Patients SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Hashash, Jana G.; Bista, Rajan; Alnabhan, Samer; Baidoo, Leonard; Brand, Randall; Liu, Yang] Univ Pittsburgh, Pittsburgh, PA USA. [Staton, Kevin D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hartman, Douglas J.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA. [Regueiro, Miguel; Swoger, Jason] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Binion, David G.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Francis, Fadi] Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1895 BP S804 EP S805 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904054 ER PT J AU Jacob, N Benhammou, J Al-Jiboury, H Patel, A Sedarat, A Lewis, M Pisegna, JR AF Jacob, Noam Benhammou, Jihane Al-Jiboury, Hala Patel, Arpan Sedarat, Alireza Lewis, Michael Pisegna, Joseph R. TI Duodenal Neuroendocrine Tumors (DNETs): A Case Series and Establishment of a Registry for Proposed Classification SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Jacob, Noam; Lewis, Michael] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Benhammou, Jihane] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Al-Jiboury, Hala; Patel, Arpan; Sedarat, Alireza] Univ Calif Los Angeles, Los Angeles, CA USA. [Pisegna, Joseph R.] Univ Calif Los Angeles, VA Greater Los Angeles Hlth Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 2425 BP S1007 EP S1008 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715905055 ER PT J AU Kalra, A Hunt, K Gross, J Kwon, W Somrov, S Gal, C Kirtich, S Aytaman, A AF Kalra, Amita Hunt, Kristel Gross, Jonathan Kwon, William Somrov, Serge Gal, Christopher Kirtich, Sabina Aytaman, Ayse TI Creation of a VISN Wide Multi-Disciplinary, Multi-Facility Team and Tumor Board: Its Impact on Timeliness and Quality of Hepatocellular Carcinoma Care SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Kalra, Amita; Gal, Christopher] SUNY Downstate, Brooklyn, NY USA. [Hunt, Kristel] James J Peters VA Med Ctr, Bronx, NY USA. [Gross, Jonathan] VA New York Harbor Hlth Care Syst, Brooklyn, NY USA. [Kwon, William] Brooklyn VA Harbor Healthcare Syst, Brooklyn, NY USA. [Somrov, Serge; Aytaman, Ayse] Brooklyn VA Harbor Healthcare Syst, Brooklyn, NY USA. [Kirtich, Sabina] Brooklyn VA, Brooklyn, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 2075 BP S872 EP S872 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904234 ER PT J AU Kassam, Z Fridman, S Burgess, J Fischer, M Amaratunga, K Edelstein, C Osman, M Noh, A Kauffman, D Dubois, N Smith, M Alm, E Ananthakrishnan, A AF Kassam, Zain Fridman, Sebastian Burgess, James Fischer, Monika Amaratunga, Kanchana Edelstein, Carolyn Osman, Majdi Noh, Andrew Kauffman, Deberly Dubois, Nancy Smith, Mark Alm, Eric Ananthakrishnan, Ashwin TI The Cost-Effectiveness of Competing Strategies for Managing Multiply Recurrent Clostridium difficile Infection: Examining the Impact of Universal Stool Banks and Encapsulated Fecal Microbiota Transplantation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Kassam, Zain; Smith, Mark; Alm, Eric] MIT, OpenBiome, Medford, MA USA. [Fridman, Sebastian] Harvard Univ, TH Chan Sch Publ Hlth, Medford, MA USA. [Burgess, James; Edelstein, Carolyn; Osman, Majdi; Noh, Andrew; Kauffman, Deberly; Dubois, Nancy] OpenBiome, Medford, MA USA. [Fischer, Monika] Indiana Univ, Dept Med, Indianapolis, IN USA. [Amaratunga, Kanchana] Ottawa Hosp, Medford, MA USA. [Ananthakrishnan, Ashwin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 2247 BP S933 EP S934 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904406 ER PT J AU Kochar, B Long, M Shelton, E Young, L Farraye, F Yajnik, V Herfarth, H AF Kochar, Bharati Long, Millie Shelton, Edward Young, Lorraine Farraye, Francis Yajnik, Vijay Herfarth, Hans TI Safety and Efficacy of Teduglutide (Gattex) in Patients With Crohn's Disease and Need for Parenteral Support Due to Short Bowel Syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Kochar, Bharati; Long, Millie; Herfarth, Hans] Univ N Carolina, Chapel Hill, NC USA. [Shelton, Edward] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Young, Lorraine; Farraye, Francis] Boston Univ, Boston, MA 02215 USA. [Yajnik, Vijay] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1912 BP S812 EP S812 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904071 ER PT J AU Leung, FW Amato, A Cadoni, S Falt, P Friedland, S Hsieh, YH Leung, J Liggi, M Sul, J Yen, A AF Leung, Felix W. Amato, Arnaldo Cadoni, Sergio Falt, Premsyl Friedland, Shai Hsieh, Yu-Hsi Leung, Joseph Liggi, Mauro Sul, James Yen, Andrew TI Novel Developments in Water-Aided Techniques for Education and Research (WATER) in Colonoscopy SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Leung, Felix W.] VA Greater Los Angeles Hth Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, North Hills, CA USA. [Amato, Arnaldo] Valduce Hosp, Como, Italy. [Cadoni, Sergio; Liggi, Mauro] S Barbara Hosp, Iglesias, CI, Italy. [Falt, Premsyl] Vitkovice Hosp, Zaluzanskeho, Czech Republic. [Friedland, Shai] Palo Alto VA Med Ctr, Palo Alto, CA USA. [Hsieh, Yu-Hsi] Tzu Chi Gen Hosp, Chiayi, Taiwan. [Leung, Joseph; Yen, Andrew] Sacramento VA Med Ctr, Mather, CA USA. [Sul, James] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1265 BP S556 EP S557 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715902364 ER PT J AU Perez, BL Trivedi, H Tandon, M Kozyreva, O AF Perez, Blanca Lizaola Trivedi, Hirsh Tandon, Manish Kozyreva, Olga TI Metronomic Chemotherapy for Elderly Patients With Advanced Gastric Cancer: A Potentially Feasible Alternative to Therapeutic Nihilism SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Perez, Blanca Lizaola; Trivedi, Hirsh; Tandon, Manish] St Elizabeths Med Ctr, Brighton, MA USA. [Kozyreva, Olga] St Elizabeths Med Ctr, Dana Farber Canc Inst, Brighton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1156 BP S504 EP S504 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715902255 ER PT J AU Snyder, D Kathpalia, P Sontag, S AF Snyder, Diana Kathpalia, Priya Sontag, Stephen TI Surveillance Colonoscopy to Detect Colorectal Cancer in Patients With Inflammatory Bowel Disease: Is It Too Frequent? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Snyder, Diana] Loyola Univ, Med Ctr, River Grove, IL USA. [Kathpalia, Priya] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA. [Sontag, Stephen] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1977 BP S837 EP S837 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904136 ER PT J AU Staller, K Barshop, K Kuo, B Ananthakrishnan, A AF Staller, Kyle Barshop, Kenneth Kuo, Braden Ananthakrishnan, Ashwin TI Restricted Eating Patterns in Chronic Constipation Are Associated With Bloating and Abdominal Symptoms More so Than Rectal and Stool Symptoms SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Staller, Kyle; Ananthakrishnan, Ashwin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Barshop, Kenneth] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Kuo, Braden] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1791 BP S761 EP S761 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715903404 ER PT J AU Staller, K Barshop, K Ananthakrishnan, A Kuo, B AF Staller, Kyle Barshop, Kenneth Ananthakrishnan, Ashwin Kuo, Braden TI Comorbid Depression, Not Symptom Severity or Disease-Specific Quality of Life, Predicts Work Absenteeism in Chronic Constipation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Staller, Kyle; Ananthakrishnan, Ashwin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Barshop, Kenneth] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Kuo, Braden] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1774 BP S754 EP S754 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715903387 ER PT J AU Staller, K Singh, P Surana, R Soni, S Agnihotri, A Makharia, G Kuo, B AF Staller, Kyle Singh, Prashant Surana, RIshabh Soni, Snigdha Agnihotri, Abhishek Makharia, Govind Kuo, Braden TI Cross Cultural Comparison of Constipation Profiles at Tertiary Care Centers Between India and USA SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Staller, Kyle] Massachusetts Gen Hosp, Swampscott, MA USA. [Singh, Prashant; Kuo, Braden] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Surana, RIshabh; Soni, Snigdha; Makharia, Govind] All India Inst Med Sci, New Delhi, India. [Agnihotri, Abhishek] All India Inst Med Sci, Jaipur, Rajasthan, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1755 BP S745 EP S745 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715903368 ER PT J AU Taleban, S Stewart, K Li, D Singh, P Sturgeon, H Nguyen, D Yajnik, V Ananthakrishnan, A Khalili, H AF Taleban, Sasha Stewart, Kathleen Li, Darrick Singh, Prashant Sturgeon, Holly Deanna Nguyen Yajnik, Vijay Ananthakrishnan, Ashwin Khalili, Hamed TI Correlations Between Clinical Activity Indices or Quality of Life Scores to Endoscopic Activity Scores Do not Vary According to Age at Diagnosis, Disease Location, and Disease Behavior in Inflammatory Bowel SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Taleban, Sasha] Univ Arizona, Sch Med, Tucson, AZ USA. [Stewart, Kathleen; Li, Darrick; Singh, Prashant; Sturgeon, Holly; Deanna Nguyen; Yajnik, Vijay; Ananthakrishnan, Ashwin; Khalili, Hamed] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1883 BP S799 EP S800 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904042 ER PT J AU Trivedi, HD Lizaola, B Kozyreva, O AF Trivedi, Hirsh D. Lizaola, Blanca Kozyreva, Olga TI A Rare Case of a Dedifferentiated Gastrointestinal Stromal Tumor Arising de novo SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Trivedi, Hirsh D.; Lizaola, Blanca] St Elizabeths Med Ctr, Brighton, MA USA. [Kozyreva, Olga] St Elizabeths Med Ctr, Dana Farber Canc Inst, Brighton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 946 BP S404 EP S404 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715902046 ER PT J AU Wang, MH Fiocchi, C Ripke, S Rebert, N Duerr, R Achkar, JP AF Wang, Ming-Hsi Fiocchi, Claudio Ripke, Stephan Rebert, Nancy Duerr, Richard Achkar, Jean-Paul TI Integrating Genetic Risk Profiles With Clinical Predictors Can Predict Need for Early Surgery in Crohn's Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Wang, Ming-Hsi; Achkar, Jean-Paul] Cleveland Clin, Dept Pathobiol, Lerner Res Inst, Cleveland, OH 44106 USA. [Wang, Ming-Hsi; Achkar, Jean-Paul] Cleveland Clin, Inst Digest Dis, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA. [Fiocchi, Claudio] Cleveland Clin, Inst Digest Dis, Dept Gastroenterol & Hepatol, Dept Pathobiol,Lerner Res Inst, Cleveland, OH 44106 USA. [Ripke, Stephan] Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA. [Rebert, Nancy] Cleveland Clin, Lerner Res Inst, Dept Pathobiol, Cleveland, OH 44106 USA. [Duerr, Richard] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1803 BP S766 EP S767 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715903416 ER PT J AU Yajnik, V Khan, N Dubinsky, M Axler, J Green, A Abhyankar, B Lasch, K AF Yajnik, Vijay Khan, Nabeel Dubinsky, Marla Axler, Jeffrey Green, Alexandra Abhyankar, Brihad Lasch, Karen TI Efficacy and Safety of Vedolizumab With Advancing Age in Patients With Crohn's Disease: Results From the GEMINI 2 Study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Yajnik, Vijay] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Khan, Nabeel] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Dubinsky, Marla] Mt Sinai Hosp, New York, NY 10029 USA. [Axler, Jeffrey] Univ Toronto, Toronto Digest Dis Associates, Toronto, ON, Canada. [Green, Alexandra; Abhyankar, Brihad] Takeda Dev Ctr Europe Ltd, London, England. [Lasch, Karen] Takeda Pharmaceut Int Inc, Deerfield, IL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1860 BP S790 EP S790 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904019 ER PT J AU Yen, AW Leung, JW Leung, FW AF Yen, Andrew W. Leung, Joseph W. Leung, Felix W. TI Underwater Resection of Colorectal Neoplasia: Taking the Plunge Into a New Technique SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Yen, Andrew W.; Leung, Joseph W.] Sacramento VA Med Ctr, Mather, CA USA. [Yen, Andrew W.; Leung, Joseph W.] Univ Calif Davis, Sch Med, Mather, CA USA. [Leung, Felix W.] VA Greater Los Angeles Hlth Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA. [Leung, Felix W.] UCLA, David Geffen Sch Med, North Hills, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1593 BP S686 EP S686 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715903206 ER PT J AU Baan, M Kibbe, CR Bushkofsky, JR Harris, TW Sherman, DS Davis, DB AF Baan, Mieke Kibbe, Carly R. Bushkofsky, Justin R. Harris, Ted W. Sherman, Dawn S. Davis, Dawn Belt TI Transgenic expression of the human growth hormone minigene promotes pancreatic beta-cell proliferation SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE human growth hormone; transgene expression; FoxM1; beta-cell; proliferation ID TRANSCRIPTION FACTOR; PARATHYROID-HORMONE; DIABETES SUSCEPTIBILITY; GLUCOSE-HOMEOSTASIS; ISLET MASS; TGF-ALPHA; MICE; PROTEIN; LIVER; OVEREXPRESSION AB Transgenic mouse models are designed to study the role of specific proteins. To increase transgene expression the human growth hormone (hGH) minigene, including introns, has been included in many transgenic constructs. Until recently, it was thought that the hGH gene was not spliced, transcribed, and translated to produce functional hGH protein. We generated a transgenic mouse with the transcription factor Forkhead box M1 (FoxM1) followed by the hGH minigene, under control of the mouse insulin promoter (MIP) to target expression specifically in the pancreatic beta-cell. Expression of FoxM1 in isolated pancreatic islets in vitro stimulates beta-cell proliferation. We aimed to investigate the effect of FoxM1 on beta-cell mass in a mouse model for diabetes mellitus. However, we found inadvertent coexpression of hGH protein from a spliced, bicistronic mRNA. MIP-FoxM1-hGH mice had lower blood glucose and higher pancreatic insulin content, due to increased beta-cell proliferation. hGH signals through the murine prolactin receptor, and expression of its downstream targets tryptophan hydroxylase-1 (Tph1), tryptophan hydroxylase-2 (Tph2), and cytokine-inducible SH2 containing protein (Cish) was increased. Conversely, transcriptional targets of FoxM1 were not upregulated. Our data suggest that the phenotype of MIP-FoxM1-hGH mice is due primarily to hGH activity and that the FoxM1 protein remains largely inactive. Over the past decades, multiple transgenic mouse strains were generated that make use of the hGH minigene to increase transgene expression. Our work suggests that each will need to be carefully screened for inadvertent hGH production and critically evaluated for the use of proper controls. C1 [Baan, Mieke; Kibbe, Carly R.; Bushkofsky, Justin R.; Harris, Ted W.; Sherman, Dawn S.; Davis, Dawn Belt] Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI USA. [Davis, Dawn Belt] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Davis, DB (reprint author), 4147 MFCB,1685 Highland Ave, Madison, WI 53705 USA. EM dbd@medicine.wisc.edu FU National Institutes of Health [T32 RR023916, T32 OD010423, T32AG000213]; NIDDK [DK083442]; University of Wisconsin Department of Medicine FX This work was supported by the National Institutes of Health training grants T32 RR023916 (MB), T32 OD010423 (MB), and T32AG000213 (CK). DBD was supported by NIDDK DK083442 and the University of Wisconsin Department of Medicine. This work was performed with facilities and resources from the William S. Middleton Memorial Veterans Hospital. This work does not represent the views of the Department of Veterans Affairs or the United States government. NR 39 TC 2 Z9 2 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD OCT 1 PY 2015 VL 309 IS 7 BP R788 EP R794 DI 10.1152/ajpregu.00244.2015 PG 7 WC Physiology SC Physiology GA CV2QT UT WOS:000364102200009 PM 26202070 ER PT J AU Macqueen, IT Shannon, EM Dawes, AJ Ostrzega, N Russell, MM Maggard-Gibbons, M AF Macqueen, Ian T. Shannon, Evan M. Dawes, Aaron J. Ostrzega, Nora Russell, Marcia M. Maggard-Gibbons, Melinda TI The Role of Surgery in the Clinical Management of Primary Gastrointestinal Non-Hodgkin's Lymphoma SO AMERICAN SURGEON LA English DT Article ID PRIMARY GASTRIC LYMPHOMA; PRIMARY COLONIC LYMPHOMA; CONSERVATIVE MANAGEMENT; GERMAN MULTICENTER; SURVIVAL; OUTCOMES; DISEASE; TRACT AB Primary gastrointestinal non-Hodgkin's lymphoma (PGINHL) is a heterogeneous family of tumors, with treatment modalities including chemotherapy, surgery, and radiotherapy. Because the role of surgery in PGINHL remains disputed, this study aims to assess the impact of operative resection on survival. We used a pathology database to identify all cases of PGINHL diagnosed at a single academic-affiliated medical center from 1988 to 2013. Demographic and clinical data were abstracted from the medical record. We summarized the clinical courses of patients with PGINHL and then performed a survival analysis to compare overall and disease-free survival, stratified by demographic and clinical variables. We identified 33 patients diagnosed with PGINHL during the study period. Of 29 who subsequently received treatment at the institution, 15 initially underwent chemotherapy, 10 underwent surgical resection, and 4 underwent surgery for other reasons such as diagnosis without resection or management of disease complications. Three patients suffered surgical complications and two of these patients died. We found no difference in overall survival between patients receiving surgical resection and patients managed initially with chemotherapy. This case series supports a continued role for surgical resection in the management of patients with PGINHL, though anticipated benefits should be weighed against the risk of complications. C1 [Macqueen, Ian T.; Russell, Marcia M.; Maggard-Gibbons, Melinda] Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Macqueen, Ian T.; Dawes, Aaron J.; Russell, Marcia M.; Maggard-Gibbons, Melinda] VA Greater Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Shannon, Evan M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dawes, Aaron J.] VA Robert Wood Johnson Fdn, Clin Scholars Program, Los Angeles, CA USA. [Ostrzega, Nora] Olive View UCLA, Dept Pathol, Med Ctr, Sylmar, CA USA. [Maggard-Gibbons, Melinda] Olive View UCLA, Dept Surg, Med Ctr, Sylmar, CA USA. RP Macqueen, IT (reprint author), Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Ronald Reagan UCLA,Med Ctr, 757 Westwood Plaza,B711, Los Angeles, CA 90095 USA. EM imacqueen@mednet.ucla.edu FU Department of Veterans Affairs; VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program FX MacQueen was supported by the Department of Veterans Affairs. Dawes was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program. NR 24 TC 1 Z9 1 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD OCT PY 2015 VL 81 IS 10 BP 988 EP 994 PG 7 WC Surgery SC Surgery GA CV0LE UT WOS:000363941400016 PM 26463295 ER PT J AU Dawes, AJ Reardon, S Chen, VL Kaiser, W Russell, MM Ko, CY Lin, AY AF Dawes, Aaron J. Reardon, Sarah Chen, Victor L. Kaiser, William Russell, Marcia M. Ko, Clifford Y. Lin, Anne Y. TI Wireless Technology to Track Surgical Patients after Discharge: A Pilot Study SO AMERICAN SURGEON LA English DT Article ID COLORECTAL SURGERY; RISK-FACTORS; READMISSION; IMPROVEMENT; INTERNET; RATES AB Failure to detect changes in patients' postoperative health status increases the risk of adverse outcomes, including complications and readmission. We sought to design and implement a real-time surveillance system for postoperative colorectal surgery patients using wireless health technology. Participants were assigned a preprogrammed tablet computer during their inpatient hospitalization, and asked to complete a daily survey regarding their postoperative health status until their first clinic visit. Surveys were transmitted wirelessly to a secure database for review. As a pilot study, we report on our first 20 consecutively enrolled patients, monitored for 265 patient days. Overall compliance was 63 per cent (data available for 166 of the 265 days), but varied by patient from 26 to 100 per cent. We were able to reliably collect basic data on postoperative health status as well as patient-reported outcomes not previously captured by standard assessment techniques. Qualitative data suggest that the experience strengthened patients' relationship with their surgeon and aided in their recovery. Postoperative remote monitoring is feasible, and provides more detailed and complete information to the clinical team. Wireless health technology represents an opportunity to close the information gap between discharge and first clinic visit, and, eventually, to improve patient-provider communication, increase patient satisfaction, and prevent unnecessary readmissions. C1 [Dawes, Aaron J.; Reardon, Sarah; Russell, Marcia M.; Ko, Clifford Y.; Lin, Anne Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Russell, Marcia M.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dawes, Aaron J.] Univ Calif Los Angeles, VA Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. [Chen, Victor L.; Kaiser, William] Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA. [Chen, Victor L.; Kaiser, William] Univ Calif Los Angeles, Wireless Hlth Inst, Los Angeles, CA 90095 USA. RP Dawes, AJ (reprint author), Univ Calif Los Angeles, Ronald Reagan UCLA Med Ctr, David Geffen Sch Med, Dept Surg, 757 Westwood Plaza,B711, Los Angeles, CA 90095 USA. EM adawes@mednet.ucla.edu FU VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program FX AJD was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program. NR 22 TC 0 Z9 0 U1 1 U2 2 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD OCT PY 2015 VL 81 IS 10 BP 1061 EP 1066 PG 6 WC Surgery SC Surgery GA CV0LE UT WOS:000363941400030 PM 26463309 ER PT J AU MacQueen, IT Dawes, AJ Hadnott, T Strength, K Moran, GJ Holschneider, C Russell, MM Maggard-Gibbons, M AF MacQueen, Ian T. Dawes, Aaron J. Hadnott, Tracy Strength, Kristen Moran, Gregory J. Holschneider, Christine Russell, Marcia M. Maggard-Gibbons, Melinda TI Use of a Hospital-Wide Screening Program for Early Detection of Sepsis in General Surgery Patients SO AMERICAN SURGEON LA English DT Article ID SEPTIC SHOCK; RANDOMIZED-TRIAL; CARE AB Sepsis remains a significant source of mortality among hospitalized patients. This study examines the usage of a vital sign-based screening protocol in identifying postoperative patients at risk for sepsis at an academic-affiliated medical center. We identified all general surgery inpatients undergoing abdominopelvic surgery from January to June 2014, and compared those with positive screening tests to a sample of screen-negative controls. Multivariate logistic regression was used to identify predictors of positive screening tests and progression to severe sepsis. In total, 478 patients underwent abdominopelvic operations, 59 had positive screening tests, 33 qualified for sepsis, and six progressed to severe sepsis. Predictors of a positive screening test were presence of cancer [odds ratio (OR) 30.7, 95% confidence interval (CI) 2.2-420], emergency operation (OR 6.5, 95% CI 1.7-24), longer operative time (OR 2.2/h, 95% CI 1.2-4.1), and presence of postoperative infection (OR 6.4, 95% CI 1.5-27). The screening protocol had sensitivity 100 per cent and specificity 88 per cent for severe sepsis. We identified no predictors of severe sepsis. In conclusion, vital sign-based screening provides value by drawing early attention to patients with potential to develop sepsis, but escalation of care for these patients should be based on clinical judgment. C1 [MacQueen, Ian T.; Dawes, Aaron J.; Russell, Marcia M.; Maggard-Gibbons, Melinda] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [MacQueen, Ian T.; Dawes, Aaron J.; Russell, Marcia M.; Maggard-Gibbons, Melinda] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Dawes, Aaron J.] VA Robert Wood Johnson Fdn Clin Scholars Program, Los Angeles, CA USA. [Hadnott, Tracy; Holschneider, Christine] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Strength, Kristen] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Moran, Gregory J.] Olive View UCLA Med Ctr, Dept Emergency Med, Sylmar, CA 91342 USA. [Moran, Gregory J.] Olive View UCLA Med Ctr, Dept Infect Dis, Sylmar, CA 91342 USA. [Holschneider, Christine] Olive View UCLA Med Ctr, Dept Obstet & Gynecol, Sylmar, CA 91342 USA. [Maggard-Gibbons, Melinda] Olive View UCLA Med Ctr, Dept Surg, Sylmar, CA 91342 USA. RP MacQueen, IT (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ronald Reagan UCLA Med Ctr, Dept Surg, 757 Westwood Plaza,B711, Los Angeles, CA 90095 USA. EM imacqueen@mednet.ucla.edu FU Department of Veterans Affairs; VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program FX ITM was supported by the Department of Veterans Affairs. AJD was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program. Judy McGee and Karla Nungaray were instrumental in the collection of our data. NR 9 TC 1 Z9 1 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD OCT PY 2015 VL 81 IS 10 BP 1074 EP 1079 PG 6 WC Surgery SC Surgery GA CV0LE UT WOS:000363941400032 PM 26463311 ER PT J AU Hoffman, RM Shi, Y Freedland, SJ Keating, NL Walter, LC AF Hoffman, Richard M. Shi, Ying Freedland, Stephen J. Keating, Nancy L. Walter, Louise C. TI Treatment patterns for older veterans with localized prostate cancer SO CANCER EPIDEMIOLOGY LA English DT Article DE Prostatic neoplasms; Prostatectomy; Radiotherapy; Watchful waiting; Aged; Physician's practice patterns ID RADICAL PROSTATECTOMY; ANDROGEN DEPRIVATION; MEN; RISK; MANAGEMENT; ANTIGEN; SURVIVAL; OUTCOMES; THERAPY; UPDATE AB Objective: Concerns about over-treatment have led to practice guidelines discouraging active treatment of prostate cancer (PCa) in men with limited life expectancies and/or low-risk tumors. We evaluated treatment patterns for older veterans with localized PCa, particularly those with low-risk features. Methods: We used VA Cancer Registry data to identify men aged 65+ diagnosed with clinically localized PCa between January 1st, 2003 and December 31st, 2008. We obtained baseline data on demographics, tumor characteristics, comorbidities, and initial treatment within 6 months of diagnosis: radical prostatectomy, radiotherapy, primary androgen-deprivation therapy (PADT), or no active treatment. National VA surveys provided facility data, including academic affiliation, availability of oncologic specialists, and distance to radiotherapy facilities. Multinomial regression analyses determined associations between patient and facility characteristics and cancer treatment for men with localized (stage < III) and low-risk PCa (stage <= IIa, PSA < 10 ng/mL, Gleason <= 6). Results: 17,206 veterans had localized PCa, 32% age 75+, 12% had comorbidity scores >= 3, and 33% had low-risk tumors. Overall, 39% received radiotherapy, 6% surgery, 20% PADT, and 35% no active treatment. For those with low-risk cancers, older men (RR = 0.36, 95% CI 0.30-0.43) and sicker men (RR = 0.75, 95% CI 0.62-0.90) were less likely to receive surgery or radiotherapy versus no active treatment. Over time, more of these men received no active treatment (from 41% to 57%, P < 0.001) while fewer received PADT (from 11% to 4%, P < 0.001). Conclusion: VA treatment patterns followed evidence-based guidelines against treating older and sicker men with surgery or radiotherapy, for decreasing use of PADT, and for increasingly withholding active treatment, particularly for men with low-risk PCa. Published by Elsevier Ltd. C1 [Hoffman, Richard M.] Univ Iowa, Carver Coll Med, Dept Med, Iowa City, IA 52242 USA. [Shi, Ying; Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Shi, Ying; Walter, Louise C.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Freedland, Stephen J.] Cedars Sinai Med Ctr, Dept Surg, Div Urol, Los Angeles, CA 90048 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Hoffman, RM (reprint author), Univ Iowa, Carver Coll Med, Dept Med, Iowa City, IA 52242 USA. EM richard-m-hoffman@uoiwa.edu; Ying.Shi2@va.gov; stephen.freedland@cshs.org; keating@hcp.med.harvard.edu; louise.walter@ucsf.edu FU National Cancer Institute at the National Institutes of Health [R01CA134425]; National Institute on Aging at the National Institutes of Health [K24AG041180]; New Mexico Veterans Affairs Health Care System; Prostate Cancer Foundation FX Grant R01CA134425 from the National Cancer Institute at the National Institutes of Health (LCW, SJF, RMH), grant K24AG041180 from the National Institute on Aging at the National Institutes of Health (LCW), the New Mexico Veterans Affairs Health Care System (RMH), and the Prostate Cancer Foundation (NLK). NR 35 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 EI 1877-783X J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD OCT PY 2015 VL 39 IS 5 BP 769 EP 777 DI 10.1016/j.canep.2015.07.005 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CV0PQ UT WOS:000363953300015 PM 26228494 ER PT J AU Mehra, R Gottlieb, DJ AF Mehra, Reena Gottlieb, Daniel J. TI A Paradigm Shift in the Treatment of Central Sleep Apnea in Heart Failure SO CHEST LA English DT Editorial Material ID CHEYNE-STOKES RESPIRATION; POSITIVE AIRWAY PRESSURE; SERVO-VENTILATION; MORTALITY; OUTCOMES; DESIGN; RISK C1 [Mehra, Reena] Case Western Reserve Univ, Cleveland Clin, Cleveland Clin Lerner Coll Med, Cleveland, OH 44195 USA. [Gottlieb, Daniel J.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Gottlieb, Daniel J.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Mehra, R (reprint author), Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, Sleep Disorders Res, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM mehrar@ccf.org OI Mehra, Reena/0000-0002-6222-2675 NR 21 TC 4 Z9 4 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 BP 848 EP 851 DI 10.1378/chest.15-1536 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CV0QN UT WOS:000363956300018 PM 26258890 ER PT J AU Zaremba, S Mueller, N Heisig, AM Shin, CH Jung, S Leff, LR Bateman, BT Pugsley, LJ Nagasaka, Y Duarte, IM Ecker, RL Eikermann, M AF Zaremba, Sebastian Mueller, Noomi Heisig, Anne M. Shin, Christina H. Jung, Stefanie Leff, Lisa R. Bateman, Brian T. Pugsley, Lori J. Nagasaka, Yasuko Duarte, Ingrid Moreno Ecker, Rey L. Eikermann, Matthias TI Elevated Upper Body Position Improves Pregnancy-Related OSA Without Impairing Sleep Quality or Sleep Architecture Early After Delivery SO CHEST LA English DT Article ID UPPER AIRWAY; UNITED-STATES; RISK-FACTORS; FLUID SHIFT; APNEA; POSTURE; PREVALENCE; POSTPARTUM; RESISTANCE; SEVERITY AB BACKGROUND: During pregnancy, upper airway resistance is increased, predisposing vulnerable women to pregnancy-related OSA. Elevation of the upper body increases upper airway cross-sectional area (CSA) and improves severity of OSA in a subgroup of nonpregnant patients (positional-dependent sleep apnea). We tested the hypothesis that elevated position of the upper body improves OSA early aft er delivery. METHODS: Following institutional review board approval, we conducted a randomized, crossover study on two postpartum units of Massachusetts General Hospital. Women during the first 48 h after delivery were included. Polysomnography was performed in nonelevated and 45 degrees elevated upper body position. Upper airway CSA was measured by acoustic pharyngometry in nonelevated, 45 degrees elevated, and sitting body position. RESULTS: Fifty-five patients were enrolled, and measurements of airway CSA obtained. Thirty patients completed polysomnography in both body positions. Elevation of the upper body significantly reduced apnea-hypopnea index (AHI) from 7.7 +/- 2.2/h in nonelevated to 4.5 +/- 1.4/h in 45 degrees elevated upper body position (P = .031) during sleep. Moderate to severe OSA (AHI > 15/h) was diagnosed in 20% of postpartum patients and successfully treated by elevated body position in one-half of them. Total sleep time and sleep architecture were not affected by upper body elevation. Change from nonelevated to sitting position increased inspiratory upper airway CSA from 1.35 +/- 0.1 cm(2) to 1.54 +/- 0.1 cm(2) during wakefulness. Position-dependent increase in CSA and decrease in AHI were correlated (r = 0.42, P = .022). CONCLUSIONS: Among early postpartum women, 45 degrees upper body elevation increased upper airway CSA and mitigated sleep apnea. Elevated body position might improve respiratory safety in women early aft er delivery. C1 [Zaremba, Sebastian; Mueller, Noomi; Shin, Christina H.; Jung, Stefanie; Bateman, Brian T.; Nagasaka, Yasuko; Duarte, Ingrid Moreno; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Pugsley, Lori J.; Ecker, Rey L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Bateman, Brian T.; Pugsley, Lori J.; Ecker, Rey L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Zaremba, Sebastian] Univ Bonn, Univ Hosp Bonn, Dept Neurol, Sleep Med, Bonn, Germany. [Jung, Stefanie] Univ Marburg, Teaching Hosp, DRK Kinderklinik Siegen, Dept Pediat Surg, Marburg, Germany. [Jung, Stefanie] Univ Marburg, Teaching Hosp, DRK Kinderklinik Siegen, Dept Pediat Urol, Marburg, Germany. [Bateman, Brian T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Eikermann, Matthias] Univ Duisburg Essen, Dept Anesthesia & Crit Care Med, Essen, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org FU Department of Anesthesia, Critical Care, and Pain Medicine at Massachusetts General Hospital, Boston; Buzen fund FX This study was funded by the Department of Anesthesia, Critical Care, and Pain Medicine at Massachusetts General Hospital, Boston and by an unrestricted research grant to Dr Eikermann from the Buzen fund, established by Jeffrey Buzen and Judith Buzen of Boston, Massachusetts NR 48 TC 5 Z9 5 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 BP 936 EP 944 DI 10.1378/chest.14-2973 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CV0QN UT WOS:000363956300033 PM 25905714 ER PT J AU Breyer, MD Look, AT Cifra, A AF Breyer, Matthew D. Look, A. Thomas Cifra, Alessandra TI From bench to patient: model systems in drug discovery SO DISEASE MODELS & MECHANISMS LA English DT Editorial Material ID MOUSE MODELS; STEM-CELLS; INTERVIEW; DISEASE; THERAPIES; ZEBRAFISH; CANCER; MECHANISMS AB Model systems, including laboratory animals, microorganisms, and cell- and tissue-based systems, are central to the discovery and development of new and better drugs for the treatment of human disease. In this issue, Disease Models & Mechanisms launches a Special Collection that illustrates the contribution of model systems to drug discovery and optimisation across multiple disease areas. This collection includes reviews, Editorials, interviews with leading scientists with a foot in both academia and industry, and original research articles reporting new and important insights into disease therapeutics. This Editorial provides a summary of the collection's current contents, highlighting the impact of multiple model systems in moving new discoveries from the laboratory bench to the patients' bedsides. C1 [Breyer, Matthew D.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 01864 USA. [Look, A. Thomas] Harvard Univ, Sch Med, Boston, MA 01864 USA. [Cifra, Alessandra] Co Biologists, Dis Models & Mech, Histon CB24 9LF, Cambs, England. RP Breyer, MD (reprint author), Eli Lilly & Co, Indianapolis, IN 46285 USA. EM breyer_matthew@lilly.com; thomas_look@dfci.harvard.edu NR 41 TC 0 Z9 0 U1 3 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD OCT PY 2015 VL 8 IS 10 BP 1171 EP 1174 DI 10.1242/dmm.023036 PG 4 WC Cell Biology; Pathology SC Cell Biology; Pathology GA CV0UR UT WOS:000363969500001 PM 26438689 ER PT J AU Turunen, HT Zinn, E Vandenberghe, LH AF Turunen, H. T. Zinn, E. Vandenberghe, L. H. TI Assay Conditions Significantly Alter AAV Neutralizing Antibody Determination Outcome SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Collaborative Congress of the European-Society-of-Gene-and-Cell-Therapy (ESGCT) and Finnish-Society-of-Gene-Therapy (FSGT) CY SEP 17-20, 2015 CL Helsinki, FINLAND SP European Soc Gene & Cell Therapy, Finnish Soc Gene Therapy C1 [Turunen, H. T.; Zinn, E.; Vandenberghe, L. H.] Schepens Eye Res Inst, Boston, MA USA. [Turunen, H. T.; Zinn, E.; Vandenberghe, L. H.] Massachusetts Eye & Ear Infirm, Boston, MA USA. [Turunen, H. T.; Zinn, E.; Vandenberghe, L. H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Turunen, H. T.; Zinn, E.; Vandenberghe, L. H.] Grousbeck Gene Therapy Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT 1 PY 2015 VL 26 IS 10 MA P235 BP A96 EP A96 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CU9QE UT WOS:000363878700297 ER PT J AU Turunen, HT Zinn, E Pacouret, S Vandenberghe, LH AF Turunen, H. T. Zinn, E. Pacouret, S. Vandenberghe, L. H. TI Ancestral sequence reconstruction disrupts epitopes yet preserves AAV structure and function SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Collaborative Congress of the European-Society-of-Gene-and-Cell-Therapy (ESGCT) and Finnish-Society-of-Gene-Therapy (FSGT) CY SEP 17-20, 2015 CL Helsinki, FINLAND SP European Soc Gene & Cell Therapy, Finnish Soc Gene Therapy C1 [Turunen, H. T.; Zinn, E.; Pacouret, S.; Vandenberghe, L. H.] Schepens Eye Res Inst, Boston, MA USA. [Turunen, H. T.; Zinn, E.; Pacouret, S.; Vandenberghe, L. H.] Massachusetts Eye & Ear Infirm, Boston, MA USA. [Turunen, H. T.; Zinn, E.; Pacouret, S.; Vandenberghe, L. H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Turunen, H. T.; Zinn, E.; Pacouret, S.; Vandenberghe, L. H.] Grousbeck Gene Therapy Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT 1 PY 2015 VL 26 IS 10 MA OR077 BP A27 EP A27 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CU9QE UT WOS:000363878700078 ER PT J AU Madanat, R Hussey, DK Donahue, GS Potter, HG Wallace, R Bragdon, CR Muratoglu, OK Malchau, H AF Madanat, Rami Hussey, Daniel K. Donahue, Gabrielle S. Potter, Hollis G. Wallace, Robert Bragdon, Charles R. Muratoglu, Orhun K. Malchau, Henrik TI The Symmetry of Adverse Local Tissue Reactions in Patients with Bilateral Simultaneous and Sequential ASR Hip Replacement SO JOURNAL OF ARTHROPLASTY LA English DT Article DE metal-on-metal; hip arthroplasty; bilateral; ASR; adverse local tissue reaction ID METAL-ON-METAL; IMAGING FINDINGS; ION LEVELS; MRI FINDINGS; SOFT-TISSUE; ARTHROPLASTY; PSEUDOTUMORS; FAILURE; COHORT; WEAR AB The purpose of this study was to evaluate whether patients with bilateral metal-on-metal (MoM) hip replacements have symmetric adverse local tissue reactions (ALTRs) at follow-up. An MRI of both hips was performed at a mean time of six years after surgery in 43 patients. The prevalence and severity of ALTRs were found to be similar in simultaneous hips but differences were observed in sequential hips. The order and timing of sequential hip arthroplasties did not affect the severity of ALTRs. Thus, in addition to metal ion exposure from an earlier MoM implant other factors may also play a role in the progression of ALTRs. Bilateral implants should be given special consideration in risk stratification algorithms for management of patients with MoM hip arthroplasty. (c) 2015 Elsevier Inc. All rights reserved. C1 [Madanat, Rami; Hussey, Daniel K.; Donahue, Gabrielle S.; Bragdon, Charles R.; Muratoglu, Orhun K.; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Madanat, Rami; Bragdon, Charles R.; Muratoglu, Orhun K.; Malchau, Henrik] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Potter, Hollis G.] Hosp Special Surg, Dept Radiol & Imaging, New York, NY 10021 USA. [Wallace, Robert] Sportsmed SA, Stepney, SA, Australia. RP Malchau, H (reprint author), Massachusetts Gen Hosp, Dept Orthoped, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. FU DePuy Orthopaedics, Warsaw, Indiana FX This study was supported by DePuy Orthopaedics, Warsaw, Indiana. We thank Clinical Research Project Manager Slav Lerner for his help with the study and Marc Bragdon for technical assistance. NR 31 TC 5 Z9 5 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2015 VL 30 IS 10 BP 1794 EP 1798 DI 10.1016/j.arth.2015.04.036 PG 5 WC Orthopedics SC Orthopedics GA CV0OS UT WOS:000363950800025 PM 26055146 ER PT J AU Rowell, SL Reyes, CR Malchau, H Muratoglu, OK AF Rowell, Shannon L. Reyes, Christopher R. Malchau, Henrik Muratoglu, Orhun K. TI In Vivo Oxidative Stability Changes of Highly Cross-Linked Polyethylene Bearings: An Ex Vivo Investigation SO JOURNAL OF ARTHROPLASTY LA English DT Article DE polyethylene (UHWMPE); oxidation; accelerated aging; total joint arthroplasty; retrievals ID MOLECULAR-WEIGHT POLYETHYLENE; UHMWPE ACETABULAR LINERS; MECHANICAL-PROPERTIES; GAMMA-STERILIZATION; TERM IMPLANTATION; WEAR; DEGRADATION; COMPONENTS; OSTEOLYSIS; RADICALS AB The development of highly cross-linked UHMWPEs focused on stabilizing radiation-induced free radicals as the sole precursor to oxidative degradation. However, secondary in vivo oxidation mechanisms have been discovered. After a preliminary post-operative analysis, we subjected highly cross-linked retrievals with 1-4 years in vivo durations and never-implanted controls to accelerated aging to predict the extent to which their oxidative stability was compromised in vivo. Lipid absorption, oxidation, and hydroperoxides were measured using infrared spectroscopy. Gravimetric swelling was used to measure cross-link density. After aging, all retrievals, except vitamin E-stabilized components, regardless of initial lipid levels or oxidation, showed significant oxidative degradation, demonstrated by subsurface oxidative peaks, increased hydroperoxides and decreased cross-link density, compared to their post-operative material properties and never-implanted counterparts, confirming oxidative stability changes. (c) 2015 Elsevier Inc. All rights reserved. C1 [Rowell, Shannon L.; Reyes, Christopher R.; Malchau, Henrik; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Malchau, Henrik] Sahlgrens Univ Hosp, Molndal, Sweden. [Malchau, Henrik; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ-1229, Boston, MA 02114 USA. NR 27 TC 4 Z9 4 U1 3 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2015 VL 30 IS 10 BP 1828 EP 1834 DI 10.1016/j.arth.2015.05.006 PG 7 WC Orthopedics SC Orthopedics GA CV0OS UT WOS:000363950800032 PM 26048729 ER PT J AU Edwards, MH Buehring, B AF Edwards, Mark H. Buehring, Bjoern TI Novel Approaches to the Diagnosis of Sarcopenia SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE Dysmobility; epidemiology; gait speed; grip strength; physical performance; sarcopenia ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE; SKELETAL-MUSCLE; OLDER-ADULTS; STRENGTH; MASS; ASSOCIATIONS; DEFINITION; MORTALITY AB Sarcopenia is common in older people and is associated with disability, reduced mobility, hospitalization, and various comorbidities. Although it has been recognized for over a quarter of a century, we do not currently have a universally adopted definition. This limits our ability to compare results from different studies and impedes the development of novel therapies. Although sarcopenia was initially defined purely based on low muscle mass, the importance of measures of muscle function has been realized and these have been included in recent operational definitions. These continue to evolve with some including an assessment of adiposity and others adding further components of musculoskeletal health in a score-based approach. This review describes the importance of reaching a widely accepted method to define sarcopenia in both research and clinical practice. It details the ways in which the definition has changed since its initial inception and explores how it may continue to evolve in the future. The different methods by which components of sarcopenia can be measured are described, and the various advantages and disadvantages of these techniques are evaluated. Clearly, there are several other similar syndromes in older people, such as frailty and cachexia; their relationships and overlap with sarcopenia are also explored. C1 [Edwards, Mark H.] Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England. [Buehring, Bjoern] Univ Wisconsin, Osteoporosis Res Program, Div Geriatr & Gerontol, Dept Med,Sch Med & Publ Hlth, Madison, WI USA. [Buehring, Bjoern] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. RP Edwards, MH (reprint author), Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Tremona Rd, Southampton SO16 6YD, Hants, England. EM me@mrc.soton.ac.uk RI Buehring, Bjoern/L-5581-2013 OI Buehring, Bjoern/0000-0003-3841-624X NR 25 TC 4 Z9 4 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1094-6950 EI 1559-0747 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD OCT-DEC PY 2015 VL 18 IS 4 BP 472 EP 477 DI 10.1016/j.jocd.2015.04.010 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CV4TS UT WOS:000364260000010 PM 26059568 ER PT J AU Flores, FJ Ching, SN Hartnack, K Fath, AB Purdon, PL Wilson, MA Brown, EN AF Flores, Francisco J. Ching, ShiNung Hartnack, Katharine Fath, Amanda B. Purdon, Patrick L. Wilson, Matthew A. Brown, Emery N. TI A PK-PD model of ketamine-induced high-frequency oscillations SO JOURNAL OF NEURAL ENGINEERING LA English DT Article DE ketamine; NMDAR antagonists; nonlinear least squares; pharmacokinetic; pharmacodynamic; high-frequency oscillation; in vivo recording ID NMDA RECEPTOR HYPOFUNCTION; RODENT NUCLEUS-ACCUMBENS; HYPNOTIC ACTIONS; SIMPLEX-METHOD; SPINAL-CORD; RATS; SCHIZOPHRENIA; NORKETAMINE; ANTAGONIST; DRUGS AB Objective. Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a high-frequency oscillation (HFO) which power is modulated nonlinearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PDs) of ketamine and the observed HFO power. Approach. In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by an HFO observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results. We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance. Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent range of effects that ketamine has. C1 [Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Purdon, Patrick L.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Purdon, Patrick L.; Brown, Emery N.] Harvard Univ, Sch Med, Boston, MA USA. [Flores, Francisco J.; Ching, ShiNung; Purdon, Patrick L.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Ching, ShiNung] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Fath, Amanda B.] Wellesley Coll, Wellesley, MA 02181 USA. [Wilson, Matthew A.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Flores, FJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM fjflores@neurostat.mit.edu OI Flores, Francisco/0000-0002-8974-9717 FU National Institute of Health [DP1-OD003646, 5R01MH061976, DP2-OD006454]; Career Award at the Scientific Interface from the Burroughs-Wellcome Fund FX This work has been supported by the National Institute of Health Pioneer Award DP1-OD003646 to Emery N Brown; the Career Award at the Scientific Interface from the Burroughs-Wellcome Fund to ShiNung Ching; the National Institute of Health Grant 5R01MH061976 to Matthew A Wilson, and the National Institute of Health New Innovator Award DP2-OD006454 to Patrick L Purdon. NR 49 TC 0 Z9 0 U1 0 U2 8 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD OCT PY 2015 VL 12 IS 5 AR 056006 DI 10.1088/1741-2560/12/5/056006 PG 13 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA CV3DY UT WOS:000364139800008 PM 26268223 ER PT J AU Majmudar, MD Harrington, RA Brown, NJ Graham, G McConnell, MV AF Majmudar, Maulik D. Harrington, Robert A. Brown, Nancy J. Graham, Garth McConnell, Michael V. TI Clinician Innovator: A Novel Career Path in Academic Medicine A Presidentially Commissioned Article From the American Heart Association SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE academic medicine; clinician innovator; disruption; healthcare innovation; information technology ID OUTCOMES C1 [Majmudar, Maulik D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Cardiol,Dept Med, Healthcare Transformat Lab,Corrigan Minehan Heart, Boston, MA USA. [Harrington, Robert A.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Brown, Nancy J.] Amer Heart Assoc, Dallas, TX USA. [Graham, Garth] Aetna Inc, Aetna Fdn, Hartford, CT USA. [Graham, Garth] Univ Connecticut, Sch Med, Farmington, CT USA. [McConnell, Michael V.] Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. RP Majmudar, MD (reprint author), Massachusetts Gen Hosp, Healthcare Transformat Lab, 55 Fruit St,Yawkey 5-B,Room 5-974, Boston, MA 02114 USA. EM mmajmudar@partners.org FU EchoSense; AstraZeneca; BMS; CSL Behring; GSK; Merck; Portola; Sanofi-Aventis; Medicines Company; GE Healthcare; Apple FX Dr Majmudar reports employment by Quanttus; ownership interest in Quanttus and Hi-Labs; research support from EchoSense; and being a member of the clinical advisory board of AliveCor. Dr Harrington discloses the following relationships: research grants from AstraZeneca, BMS, CSL Behring, GSK, Merck, Portola, Sanofi-Aventis, The Medicines Company; ownership interest in MyoKardia and Element Science; consulting services and/or honoraria from Adverse Events, Amgen, Daiichi-Lily, Evidint, Gilead Janssen, Medtronic, Merck, Novartis, Scanadu, The Medicines Company, Vida Health, Vox media, and WebMD. Nancy Brown has no conflicts to disclose. Dr Graham has no conflicts to disclose. Dr McConnell reports research support from GE Healthcare and Apple. NR 14 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD OCT PY 2015 VL 4 IS 10 AR e001990 DI 10.1161/JAHA.115.001990 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3IO UT WOS:000364153000009 PM 26450117 ER PT J AU Masrur, S Cox, M Bhatt, DL Smith, EE Ellrodt, G Fonarow, GC Schwamm, L AF Masrur, Shihab Cox, Margueritte Bhatt, Deepak L. Smith, Eric E. Ellrodt, Gray Fonarow, Gregg C. Schwamm, Lee TI Association of Acute and Chronic Hyperglycemia With Acute Ischemic Stroke Outcomes Post-Thrombolysis: Findings From Get With The Guidelines-Stroke SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute stroke; hyperglycemia; tissue plasminogen activator ID RANDOMIZED CONTROLLED-TRIALS; PLASMINOGEN-ACTIVATOR; INTRACEREBRAL HEMORRHAGE; GLUCOSE LEVEL; PERFORMANCE-MEASURES; THERAPY; ATTACK; RISK; CARE; PA AB Background-Hyperglycemia has been associated with adverse outcomes in patients with acute ischemic stroke (AIS) and may influence outcomes after tissue plasminogen activator (tPA). We sought to analyze the association of acute and chronic hyperglycemia on clinical outcomes in tPA-treated patients. Methods and Results-We identified 58 265 AIS patients from 1408 sites who received tPA from 2009 to 2013 in Get With The Guidelines-Stroke. Acute hyperglycemia at admission was defined as a plasma glucose level >140 mg/dL. Chronic hyperglycemia was defined by plasma glycosylated hemoglobin (HbA1c) >6.5%. Post-tPA outcomes were analyzed using logistic regression. Blood glucose >140 mg/dL and HbA1c >6.5 were associated with worse clinical outcomes (symptomatic intracranial hemorrhage [sICH], life-threatening hemorrhage, and in-hospital mortality and length of stay) in diabetic and nondiabetic patients. Among patients with documented history of diabetes, increasing admission glucose up to 200 mg/dL was associated with increased adjusted odds ratio (aOR) of in-hospital mortality (aOR, 1.07) and sICH (aOR, 1.05) per 10 mg/dL increase in blood glucose. Increasing HbA1C to 8% was associated with increased odds of in-hospital mortality (aOR, 1.19) and sICH (aOR, 1.16) per 1% increase in HbA1c. Similar findings were observed in patients without a documented history of diabetes. There was no further increase in poor outcomes above the blood glucose level of 200 mg/dL or HbA1c >8. Conclusion-Acute and chronic hyperglycemia are both associated with increased mortality and worse clinical outcomes in AIS patients treated with tPA. Controlled trials are needed to determine whether acute correction of hyperglycemia can improve outcomes after thrombolysis. C1 [Masrur, Shihab] Hartford Hosp, Hartford, CT 06102 USA. [Cox, Margueritte] Duke Clin Res Inst, Durham, NC USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USA. [Bhatt, Deepak L.; Schwamm, Lee] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. [Ellrodt, Gray] Berkshire Med Ctr, Pittsfield, MA USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Masrur, S (reprint author), Hartford Hosp, Div Cardiol, 80 Seymour St, Hartford, CT 06102 USA. EM shihabmasrur@hotmail.com FU Guidelines-Stroke program; Merck-Schering Plough Partnership (North Wales, PA); Pfizer, Inc (New York, NY) FX The Get With The Guidelines-Stroke program is supported, in part, by unrestricted educational grants to the American Heart Association by Pfizer, Inc (New York, NY) and the Merck-Schering Plough Partnership (North Wales, PA), who did not participate in the design, analysis, manuscript preparation, or approval. NR 32 TC 7 Z9 7 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD OCT PY 2015 VL 4 IS 10 AR e002193 DI 10.1161/JAHA.115.002193 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3IO UT WOS:000364153000023 PM 26408015 ER PT J AU Tan, TC Flynn, AW Chen-Tournoux, A Rudski, LG Mehrotra, P Nunes, MC Rincon, LM Shahian, DM Picard, MH Afilalo, J AF Tan, Timothy C. Flynn, Aidan W. Chen-Tournoux, Annabel Rudski, Lawrence G. Mehrotra, Praveen Nunes, Maria C. Rincon, Luis M. Shahian, David M. Picard, Michael H. Afilalo, Jonathan TI Risk Prediction in Aortic Valve Replacement: Incremental Value of the Preoperative Echocardiogram SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE aortic stenosis; aortic valve replacement; echocardiography; outcomes ID CARDIAC-SURGERY; LOW-FLOW; MITRAL REGURGITATION; EUROPEAN-ASSOCIATION; AMERICAN-SOCIETY; STENOSIS; RECOMMENDATIONS; MORTALITY; GRADIENT; TRANSCATHETER AB Background-Risk prediction is a critical step in patient selection for aortic valve replacement (AVR), yet existing risk scores incorporate very few echocardiographic parameters. We sought to evaluate the incremental predictive value of a complete echocardiogram to identify high-risk surgical candidates before AVR. Methods and Results-A cohort of patients with severe aortic stenosis undergoing surgical AVR with or without coronary bypass was assembled at 2 tertiary centers. Preoperative echocardiograms were reviewed by independent observers to quantify chamber size/function and valve function. Patient databases were queried to extract clinical data. The cohort consisted of 432 patients with a mean age of 73.5 years and 38.7% females. Multivariable logistic regression revealed 3 echocardiographic predictors of in-hospital mortality or major morbidity: E/e' ratio reflective of elevated left ventricular (LV) filling pressure; myocardial performance index reflective of right ventricular (RV) dysfunction; and small LV end-diastolic cavity size. Addition of these echocardiographic parameters to the STS risk score led to an integrated discrimination improvement of 4.1% (P<0.0001). After a median follow-up of 2 years, Cox regression revealed 5 echocardiographic predictors of all-cause mortality: small LV end-diastolic cavity size; LV mass index; mitral regurgitation grade; right atrial area index; and mean aortic gradient <40 mm Hg. Conclusions-Echocardiographic measures of LV diastolic dysfunction and RV performance add incremental value to the STS risk score and should be integrated in prediction when evaluating the risk of AVR. In addition, findings of small hypertrophied LV cavities and/or low mean aortic gradients confer a higher risk of 2-year mortality. C1 [Tan, Timothy C.; Flynn, Aidan W.; Mehrotra, Praveen; Nunes, Maria C.; Rincon, Luis M.; Shahian, David M.; Picard, Michael H.; Afilalo, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Flynn, Aidan W.] Univ Connecticut, Hartford Hosp, Hartford, CT 06112 USA. [Chen-Tournoux, Annabel; Rudski, Lawrence G.; Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Mehrotra, Praveen] Thomas Jefferson Univ Hosp, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Nunes, Maria C.] Univ Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, Brazil. [Afilalo, Jonathan] Lady Davis Inst, Ctr Clin Epidemiol, Montreal, PQ, Canada. RP Afilalo, J (reprint author), McGill Univ, Jewish Gen Hosp, Div Cardiol, 3755 Cote Ste Catherine Rd,E-222, Montreal, PQ H3T 1E2, Canada. EM jonathan.afilalo@mcgill.ca FU Fonds de recherche du Quebec en Sante (FRQ-S) FX This work was supported by a fellowship award from the Fonds de recherche du Quebec en Sante (FRQ-S), and Dr Afilalo is currently supported by a Clinical Research Scholar award from the FRQ-S. NR 36 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD OCT PY 2015 VL 4 IS 10 AR e002129 DI 10.1161/JAHA.115.002129 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3IO UT WOS:000364153000017 PM 26504147 ER PT J AU Wasfy, JH Hidrue, MK Yeh, RW Armstrong, K Dec, GW Pomerantsev, EV Fifer, MA Ferris, TG AF Wasfy, Jason H. Hidrue, Michael K. Yeh, Robert W. Armstrong, Katrina Dec, G. William, Jr. Pomerantsev, Eugene V. Fifer, Michael A. Ferris, Timothy G. TI Differences Among Cardiologists in Rates of Positive Coronary Angiograms SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE coronary angiography; outcomes research; variation analysis ID ARTERY-DISEASE; PHYSICIANS; MANAGEMENT; YIELD AB Background-Understanding the sources of variation for high-cost services has the potential to improve both patient outcomes and value in health care delivery. Nationally, the overall diagnostic yield of coronary angiography is relatively low, suggesting overutilization. Understanding how individual cardiologists request catheterization may suggest opportunities for improving quality and value. We aimed to assess and explain variation in positive angiograms among referring cardiologists. Methods and Results-We identified all cases of diagnostic coronary angiography at Massachusetts General Hospital from January 1, 2012, to June 30, 2013. We excluded angiograms for acute coronary syndrome. For each angiogram, we identified clinical features of the patients and characteristics of the requesting cardiologists. We also identified angiogram positivity, defined as at least 1 epicardial coronary stenosis >= 50% luminal narrowing. We then constructed a series of mixed-effects logistic regression models to analyze predictors of positive coronary angiograms. We assessed variation by physician in the models with median odds ratios. Over this time period, 5015 angiograms were identified. We excluded angiograms ordered by cardiologists requesting <10 angiograms. Among the remaining 2925 angiograms, 1450 (49.6%) were positive. Significant predictors of positive angiograms included age, male patients, and peripheral arterial disease. After adjustment for clinical variables only, the median odds ratio was 1.23 (95% CI 1.0-1.36), consistent with only borderline clinical variation after adjustment. In the full clinical and nonclinical model, the median odds ratio was 1.07 (95% CI 1.07-1.20), also consistent with clinically insignificant variation. Conclusions-Substantial variation exists among requesting cardiologists with respect to positive and negative coronary angiograms. After adjustment for clinical variables, there was only borderline clinically significant variation. These results emphasize the importance of risk adjustment in reporting related to quality and value. C1 [Wasfy, Jason H.; Hidrue, Michael K.; Ferris, Timothy G.] Harvard Univ, Sch Med, Massachusetts Gen Phys Org, Boston, MA USA. [Wasfy, Jason H.; Yeh, Robert W.; Dec, G. William, Jr.; Pomerantsev, Eugene V.; Fifer, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. [Armstrong, Katrina; Ferris, Timothy G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Ferris, Timothy G.] Partners Healthcare, Boston, MA USA. RP Wasfy, JH (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Phys Org, BUL-205,55 Fruit St, Boston, MA 02114 USA. EM jwasfy@mgh.harvard.edu FU Massachusetts General Hospital Physicians Organization Fellowship in Health Policy and Management FX This work was funded by the Massachusetts General Hospital Physicians Organization Fellowship in Health Policy and Management. NR 14 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD OCT PY 2015 VL 4 IS 10 AR e002393 DI 10.1161/JAHA.115.002393 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3IO UT WOS:000364153000034 PM 26475298 ER PT J AU Huynh, J Yamada, J Beauharnais, C Wenger, JB Thadhani, RI Wexler, D Roberts, DJ Bentley-Lewis, R AF Huynh, Jennifer Yamada, Jessica Beauharnais, Catherine Wenger, Julia B. Thadhani, Ravi I. Wexler, Deborah Roberts, Drucilla J. Bentley-Lewis, Rhonda TI Type 1, type 2 and gestational diabetes mellitus differentially impact placental pathologic characteristics of uteroplacental malperfusion SO PLACENTA LA English DT Article DE Placental pathology; Vasculopathy; Gestational diabetes mellitus; Type 1 diabetes mellitus; Type 2 diabetes mellitus ID REACTION PATTERNS; WOMEN; LESIONS; FETAL; REPRODUCIBILITY; NOSOLOGY; AGE; RACE/ETHNICITY; UNDERPERFUSION; CHORANGIOSIS AB Introduction: During a pregnancy complicated by diabetes, the placenta undergoes a number of functional and structural pathologic changes. However, differences across studies may reflect pathophysiologic differences of diabetes types under investigation. Methods: We examined placental pathology from women ages 18-40 years with self-identified race/ethnicity; singleton, live births; and type 1 (T1DM; n = 36), type 2 (T2DM; n = 37), or gestational diabetes mellitus (GDM; n = 126). Clinical data were abstracted from medical records. Placental diagnoses were independently re-reviewed by a perinatal pathologist. Multivariable analyses adjusting for race, gestational weight gain, gestational age, and systolic blood pressure were conducted. Results: Women with T1DM compared with either T2DM or GDM had higher gestational weight gain (mean +/- SD, T1DM vs. T2DM: 28.5 +/- 12.4 vs. 20.5 +/- 13.4 kg, p = 0.03; or GDM: 21.3 +/- 12.7 kg, p = 0.009) and insulin use (T2DM: 100.0% vs. 853%, p = 0.02; or GDM: 4.0%, p < 0.001). Women with T1DM compared with either T2DM or GDM also had a similarly lower prevalence of placental infarcts in univariate analyses; however, these findings did not remain significant after multivariable adjustment. Also, placentas from women with T2DM compared to GDM had higher rates of decidual vasculopathy when excluding women with preeclampsia (10.3 vs. 1.6%, p = 0.049) and diffuse chorangiosis (62.2 vs. 32.5%, p < 0.001) but a lower rate of villous immaturity (10.8 vs. 90.5%, p = 0.007) after full adjustment. Discussion: Placental vasculopathic abnormalities differ by maternal diabetes type, potentially reflecting underlying pathophysiologic mechanisms. Further research on placental pathology and metabolic derangements is warranted. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Huynh, Jennifer; Yamada, Jessica; Beauharnais, Catherine; Wexler, Deborah; Bentley-Lewis, Rhonda] Massachusetts Gen Hosp, Med Diabet Unit, Boston, MA 02114 USA. [Wenger, Julia B.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Med Div Nephrol, Boston, MA 02114 USA. [Roberts, Drucilla J.] Massachusetts Gen Hosp, Med Div Pathol, Boston, MA 02114 USA. RP Bentley-Lewis, R (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 4-415, Boston, MA 02114 USA. EM rbentleylewis@mgh.harvard.edu FU NIDDK NIH HHS [K24 DK094872, R03 DK096152, R03DK096152] NR 41 TC 4 Z9 4 U1 0 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 EI 1532-3102 J9 PLACENTA JI Placenta PD OCT PY 2015 VL 36 IS 10 BP 1161 EP 1166 DI 10.1016/j.placenta.2015.08.004 PG 6 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA CV4WM UT WOS:000364267200014 PM 26303757 ER PT J AU Sridharan, V Urbanski, LM Bi, WL Thistle, K Miller, MB Ramkissoon, S Reardon, DA Dunn, IF AF Sridharan, Vishwajith Urbanski, Laura M. Bi, Wenya Linda Thistle, Katrina Miller, Michael B. Ramkissoon, Shakti Reardon, David A. Dunn, Ian F. TI Multicentric Low-Grade Gliomas SO WORLD NEUROSURGERY LA English DT Article DE Astrocytoma; Ganglioglioma; Low-grade glioma; Multicentric glioma; Platelet-derived growth factor receptor amplification; Tumor progression ID GLIOBLASTOMA-MULTIFORME; RANDOMIZED-TRIAL; CANCER GENOMICS; II GLIOMAS; ASTROCYTOMA; MANAGEMENT; ORGANIZATION; PDGFRA; ADULTS AB BACKGROUND: Multicentric low-grade gliomas are rare entities that occur in disparate regions of the brain. They can present with distinct pathologic and imaging findings and may harbor a worse prognosis. We present a case of multicentric low-grade gliomas and highlight their pathogenesis, imaging characteristics, and molecular signatures, with implications for clinical management. CASE: A 49-year-old man presented with left-sided headaches for 3 months. Magnetic resonance imaging revealed concurrent non-enhancing lesions in the left medial temporal lobe and superior cerebellum. Increased size and the development of contrast enhancement in the temporal lesion promoted a left temporal craniotomy. Pathology revealing a grade II ganglioglioma. Three months later, the cerebellar lesion also acquired new contrast enhancement and was found to be a grade II astrocytoma following a supracerebellar infratentorial approach for resection. At 2 years follow-up, the patient remains clinically stable, receiving adjuvant chemotherapy for new non-enhancing, unresectable pontine lesion. CONCLUSION: Tumor growth rate, detailed pathologic findings, imaging characteristics, and molecular signatures influence the clinical course of multicentric low-grade gliomas. PDGFRA amplifications and IDH1 wild-type status may act in a concerted fashion to produce an accelerated course of radiologic changes and tumor recurrence, as noted in our case. Additional research is needed to stratify the risk of transformation in patients with multicentric low-grade glioma and to guide management strategies. C1 [Sridharan, Vishwajith; Bi, Wenya Linda; Dunn, Ian F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Miller, Michael B.; Ramkissoon, Shakti] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Urbanski, Laura M.; Bi, Wenya Linda; Thistle, Katrina] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Reardon, David A.] Harvard Univ, Sch Med, Ctr Neurooncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dunn, IF (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. EM idunn@partners.org FU NINDS NIH HHS [K08 NS087118] NR 34 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD OCT PY 2015 VL 84 IS 4 BP 1045 EP 1050 DI 10.1016/j.wneu.2015.05.021 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CV0EI UT WOS:000363920900031 PM 26004698 ER PT J AU Fitzmorris, PS Morris, JL Fettig, DM AF Fitzmorris, Paul Stephen Morris, Jason L. Fettig, David Michael TI An Unusual Presentation of Hepatocellular Carcinoma SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material C1 [Fitzmorris, Paul Stephen; Morris, Jason L.; Fettig, David Michael] Univ Alabama Birmingham, Birmingham, AL 35233 USA. [Morris, Jason L.; Fettig, David Michael] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Fitzmorris, PS (reprint author), Univ Alabama Birmingham, Birmingham, AL 35233 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 IS 10 BP 1395 EP 1395 DI 10.1038/ajg.2015.23 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KP UT WOS:000363716200003 PM 26465899 ER PT J AU Nawaz, H Koutroumpakis, E Easler, J Slivka, A Whitcomb, DC Singh, VP Yadav, D Papachristou, GI AF Nawaz, Haq Koutroumpakis, Efstratios Easler, Jeffrey Slivka, Adam Whitcomb, David C. Singh, Vijay P. Yadav, Dhiraj Papachristou, Georgios I. TI Elevated Serum Triglycerides are Independently Associated With Persistent Organ Failure in Acute Pancreatitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID FREE FATTY-ACIDS; HYPERLIPIDEMIC PANCREATITIS; HYPERTRIGLYCERIDEMIC PANCREATITIS; NECROTIZING PANCREATITIS; RESPIRATORY-FAILURE; CURRENT KNOWLEDGE; RISK-FACTOR; CLASSIFICATION; MANAGEMENT; NECROSIS AB OBJECTIVES: Hypertriglyceridemia (HTG) represents a major health problem with prevalence exceeding 30% in the U.S. The present study aims to assess the effect of elevated serum triglyceride (TG) levels on the severity of acute pancreatitis (AP). METHODS: Prospectively enrolled AP patients were categorized into normal, mild, moderate, and severe/very severe categories based on their TG levels and compared in respect to demographics, comorbidities, and clinical outcomes. Multivariate analysis determined whether elevated TG levels were independently associated with persistent organ failure. RESULTS: Two hundred and one out of 400 AP patients had serum TGs measured within 72 h of presentation, of which 115 had normal TG levels and 86 HTG (20 mild, 41 moderate, and 25 severe/very severe). Patients with HTG were of younger age (44 vs. 52 years), predominantly male (65% vs. 45%), obese (57% vs. 34%), diabetic (38% vs. 17%), and developed more frequently persistent organ failure (40% vs. 17%) compared with those with normal TGs (P<0.02). The rate of persistent organ failure increased proportionally with HTG severity grades (17% when normal TGs, 30% in mild, 39% in moderate, and 48% in severe/very severe HTG, P-trend<0.001). On multivariate analysis controlling for age, gender, body mass index, diabetes, and alcohol etiology, moderate HTG (odds ratio (OR), 2.6; P=0.04) and severe/very severe HTG (OR, 4.9; P=0.009) were independently associated with persistent organ failure. CONCLUSIONS: Elevated serum TGs in AP patients are independently and proportionally correlated with persistent organ failure regardless of etiology. TG-mediated lipotoxicity may be an attractive target to design novel interventions for severe AP. C1 [Nawaz, Haq; Koutroumpakis, Efstratios; Easler, Jeffrey; Slivka, Adam; Whitcomb, David C.; Yadav, Dhiraj; Papachristou, Georgios I.] Univ Pittsburgh, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Singh, Vijay P.] Mayo Clin, Dept Med, Div Gastroenterol, Scottsdale, AZ USA. [Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Div Gastroenterol, Dept Med, Pittsburgh, PA USA. RP Papachristou, GI (reprint author), Univ Pittsburgh, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. EM papachri@pitt.edu FU Veterans Affairs Merit Review Award [IQ1CX000272-Q1A2] FX The study was supported by a Veterans Affairs Merit Review Award (IQ1CX000272-Q1A2: PI: G.I.P). NR 41 TC 10 Z9 11 U1 4 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 IS 10 BP 1497 EP 1503 DI 10.1038/ajg.2015.261 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KP UT WOS:000363716200018 PM 26323188 ER PT J AU Liu, JJ Brodley, CE Healy, BC Chitnis, T AF Liu, Jingjing Brodley, Carla E. Healy, Brian C. Chitnis, Tanuja TI Removing confounding factors via constraint-based clustering: An application to finding homogeneous groups of multiple sclerosis patients SO ARTIFICIAL INTELLIGENCE IN MEDICINE LA English DT Article DE Constraint-based clustering; Confounding factor; Mining medical data; Physician subjectivity; Multiple sclerosis ID AGE; DIAGNOSIS; DISEASE; MODEL; SEX AB Objectives: Confounding factors in unsupervised data can lead to undesirable clustering results. For example in medical datasets, age is often a confounding factor in tests designed to judge the severity of a patient's disease through measures of mobility, eyesight and hearing. In such cases, removing age from each instance will not remove its effect from the data as other features will be correlated with age. Motivated by the need to find homogeneous groups of multiple sclerosis (MS) patients, we apply our approach to remove physician subjectivity from patient data. Methods: We present a method based on constraint-based clustering to remove the impact of such confounding factors. Given knowledge about which feature (or set of features) is a confounding factor, call it F. Our method first partitions the data into b bins: if F is categorical, instances from the same category construct one bin; if F is numeric, then we split bins such that each bin contains instances of similar F value. Thus each instance is assigned to a single bin for factor F. We then remove feature F from each instance for the remaining steps. Next, we cluster the data separately in each bin. Using these clustering results, we generate pair-wise constraints and then run a constraint-based clustering algorithm to produce a final grouping. Results: In a series of experiments with synthetic datasets, we compare our proposed methods to detrending when one has numeric confounding factors. We apply our method to the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Womens Hospital dataset, and find a novel grouping of patients that can help uncover the factors that impact disease progression in MS. Conclusions: Our method groups data removing the effect of confounding factors without making any assumptions about the form of the influence of these factors on the other features. We identified clusters of MS patients that have clinically recognizable differences. Because patients more likely to progress are found using this approach, our results have the potential to aid physicians in tailoring treatment decisions for MS patients. (C) 2015 Elsevier B.V. All rights reserved. C1 [Liu, Jingjing] Tufts Univ, Dept Comp Sci, Medford, MA 02155 USA. [Brodley, Carla E.] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Chitnis, Tanuja] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Brookline, MA 02115 USA. RP Brodley, CE (reprint author), Northeastern Univ, Coll Comp & Informat Sci, 440 Huntington Ave,202 West Village H, Boston, MA 02115 USA. EM jliu02@tufts.edu; c.brodley@neu.edu; bchealy@partners.org; tchitnis@rics.bwh.harvard.edu FU NSF [IIS-0803409]; National Multiple Sclerosis Society [PP1873]; National MS Society [RG-4256A4/2] FX Carla Brodley and Jingjing Liu were supported by support from the NSF (IIS-0803409) and by a pilot research award from the National Multiple Sclerosis Society (PP1873). Tanuja Chitnis and Brian C. Healey were supported in part by grants from the National MS Society (RG-4256A4/2). NR 45 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0933-3657 EI 1873-2860 J9 ARTIF INTELL MED JI Artif. Intell. Med. PD OCT PY 2015 VL 65 IS 2 SI SI BP 79 EP 88 DI 10.1016/j.artmed.2015.06.004 PG 10 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA CU8XH UT WOS:000363826900002 PM 26253753 ER PT J AU Anyanwu, CO Fiorentino, DF Chung, L Dzuong, C Wang, Y Okawa, J Carr, K Propert, KJ Werth, VP AF Anyanwu, C. O. Fiorentino, D. F. Chung, L. Dzuong, C. Wang, Y. Okawa, J. Carr, K. Propert, K. J. Werth, V. P. TI Validation of the Cutaneous Dermatomyositis Disease Area and Severity Index: characterizing disease severity and assessing responsiveness to clinical change SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID QUALITY-OF-LIFE; OUTCOME MEASURES; LUPUS-ERYTHEMATOSUS; RELIABILITY; INSTRUMENT; VALIDITY AB Background The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) was developed for use in clinical trials and longitudinal patient assessment. Objectives To characterize disease severity using the CDASI and assess the responsiveness of this instrument to clinically meaningful changes in disease activity. Methods Patients with cutaneous dermatomyositis at the University of Pennsylvania (UPenn, n = 93) and Stanford University (Stanford, n = 106) were prospectively evaluated using the CDASI, physician global assessment (PGA) Likert scales and a visual analogue scale (VAS). Data was analysed using logistic regression models and receiver operating characteristic curves to select cut-offs. Results Baseline CDASI activity scores for the patients evaluated at UPenn ranged from 0 to 47 (median 17), and baseline PGA VAS scores ranged from 0 to 9.6 (median 1.1). At UPenn a CDASI activity score of 19 differentiated mild from moderate and severe disease. At Stanford baseline CDASI scores ranged from 0 to 48 (median 21), baseline PGA VAS scores ranged from 0 to 9.7 (median 4.2) and CDASI activity scores of 14 or less characterized mild disease. When a 2-cm change in the PGA VAS was regarded as a clinically significant improvement, a 4-point (UPenn) or 5-point (Stanford) change in CDASI reflected a minimal clinically significant response. Conclusions The CDASI is a valid and responsive measure that can be used to characterize cutaneous dermatomyositis severity and detect improvement in disease activity. Variations in cut-offs may be due to differences in disease severity between the two populations or inter-rater variations in the use of the external gold measures. C1 [Anyanwu, C. O.; Werth, V. P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Anyanwu, C. O.; Okawa, J.; Carr, K.; Werth, V. P.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Fiorentino, D. F.; Chung, L.; Dzuong, C.] Stanford Univ, Div Immunol & Rheumatol, Dept Dermatol & Med, Sch Med, Stanford, CA 94305 USA. [Wang, Y.; Propert, K. J.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; National Institutes of Health [NIH K24-AR 02207, UL1000003] FX This project is supported by the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development and by the National Institutes of Health [NIH K24-AR 02207 (V.P.W.); UL1000003 (K.J.P.)]. NR 15 TC 6 Z9 6 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD OCT PY 2015 VL 173 IS 4 BP 969 EP 974 DI 10.1111/bjd.13915 PG 6 WC Dermatology SC Dermatology GA CU9WG UT WOS:000363896800020 PM 25994337 ER PT J AU Clauss, S Ellinor, PT AF Clauss, Sebastian Ellinor, Patrick T. TI Does Atrial Fibrillation Follow Function? Ion Channel Mutations and Lone Atrial Fibrillation SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Editorial Material DE Editorial; atrial fibrillation; electrophysiology; genetics; human; ion channel; mutation ID HIGH PREVALENCE; VARIANTS; RARE; EPIDEMIOLOGY C1 [Clauss, Sebastian; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Clauss, Sebastian] Univ Munich LMU, Dept Med 1, Klinikum Grosshadern, Munich, Germany. [Clauss, Sebastian] DZHK German Ctr Cardiovasc Res, Berlin, Germany. [Ellinor, Patrick T.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Program Med Populat Genet, Broad Inst Harvard & MIT, Boston, MA 02129 USA. EM ellinor@mgh.harvard.edu FU NHLBI NIH HHS [R01HL128914, R01HL092577, R01 HL092577, R01 HL128914, K24HL105780, K24 HL105780] NR 13 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD OCT PY 2015 VL 8 IS 5 BP 1005 EP 1006 DI 10.1161/CIRCEP.115.003330 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU2SP UT WOS:000363374100003 PM 26487618 ER PT J AU Turakhia, MP Ziegler, PD Schmitt, SK Chang, YC Fan, J Than, CT Keung, EK Singer, DE AF Turakhia, Mintu P. Ziegler, Paul D. Schmitt, Susan K. Chang, Yuchiao Fan, Jun Than, Claire T. Keung, Edmund K. Singer, Daniel E. TI Atrial Fibrillation Burden and Short-Term Risk of Stroke Case-Crossover Analysis of Continuously Recorded Heart Rhythm From Cardiac Electronic Implanted Devices SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; cross-over studies; defibrillators; implantable; stroke; United States Department of Veterans Affairs ID TEMPORAL RELATIONSHIP; TREAT-AF; ANTICOAGULATION; THERAPY; EVENTS; TACHYARRHYTHMIAS; DEFIBRILLATOR; ACCURACY; TRENDS AB Background The temporal relationship of atrial fibrillation (AF) and stroke risk is controversial. We evaluated this relationship via a case-crossover analysis of ischemic strokes in a large cohort of patients with cardiac implantable electronic devices. Methods and Results We identified 9850 patients with cardiac implantable electronic devices remotely monitored in the Veterans Administration Health Care System between 2002 and 2012. There were 187 patients with acute ischemic stroke and continuous heart rhythm monitoring for 120 days before the stroke (age, 698.4 years; 98% with an implantable defibrillator). We compared each patient's daily AF burden in the 30 days before stroke (case period) with their AF burden during days 91 to 120 pre stroke (control period). Defining positive AF burden as 5.5 hours of AF on any given day, 156 patients (83%) had no positive AF burden in both periods and, in fact, had little to no AF; 15 (8%) patients had positive AF burden in both periods. Among the discordant (informative) patients, 13 exceeded 5.5 hours of AF in the case period but not in the control period, whereas 3 had positive AF burden in the control but not in the case period (warfarin-adjusted odds ratio for stroke, 4.2; 95% confidence interval, 1.5-13.4). Odds ratio for stroke was highest (17.4; 95% confidence interval, 5.39-73.1) in the 5 days immediately after a qualifying occurrence of AF and decreased toward 1.0 as the period after the AF occurrence increased beyond 30 days. Conclusions In this population with continuous heart rhythm recording, multiple hours of AF had a strong but transient effect raising stroke risk. C1 [Turakhia, Mintu P.; Schmitt, Susan K.; Fan, Jun; Than, Claire T.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Turakhia, Mintu P.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Ziegler, Paul D.] Medtron Cardiac Rhythm Dis Management, Mounds View, MN USA. [Keung, Edmund K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Chang, Yuchiao; Singer, Daniel E.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Chang, Yuchiao; Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. RP Turakhia, MP (reprint author), VA Palo Alto Hlth Care Syst, 3801 Miranda Ave,111C, Palo Alto, CA 94304 USA. EM mintu@stanford.edu FU Veterans Health Services Research & Development Career Development Award [CDA09027-1]; VA Health Services Research and Development [IIR 09-092, RRP 12-517]; Medtronic Inc; American Heart Association [09SDG2250647]; Jeffrey Thomas Stroke Shield Foundation; Massachusetts General Hospital; Medtronic, Inc; Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital FX Dr Turakhia was supported by a Veterans Health Services Research & Development Career Development Award (CDA09027-1). This project was supported by grants from VA Health Services Research and Development (IIR 09-092; RRP 12-517), Medtronic Inc, American Heart Association Scientist Development Grant (09SDG2250647), and Jeffrey Thomas Stroke Shield Foundation. Dr Singer was supported by a contract between Massachusetts General Hospital and Medtronic, Inc, and by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital. The sponsors had no role in the study design or data analysis. NR 26 TC 24 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD OCT PY 2015 VL 8 IS 5 BP 1040 EP 1047 DI 10.1161/CIRCEP.114.003057 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU2SP UT WOS:000363374100010 PM 26175528 ER PT J AU Gill, SV Vessali, M Pratt, JA Watts, S Pratt, JS Raghavan, P DeSilva, JM AF Gill, Simone V. Vessali, Misha Pratt, Jacob A. Watts, Samantha Pratt, Janey S. Raghavan, Preeti DeSilva, Jeremy M. TI The Importance of Interdisciplinary Research Training and Community Dissemination SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Editorial Material DE interdisciplinary; research; education ID SCIENCE; BREAK AB Funding agencies and institutions are creating initiatives to encourage interdisciplinary research that can be more easily translated into community initiatives to enhance health. Therefore, the current research environment calls for interdisciplinary education and skills to create sustained partnerships with community institutions. However, formalized opportunities in both of these areas are limited for students embarking on research careers. The purpose of this paper is to underscore the historical and current importance of providing interdisciplinary training and community dissemination for research students. We also suggest an approach to begin to address the existing gap. Specifically, we suggest embedding a 10-week summer rotation into existing research curricula with the goals of: (1) providing students with a hands-on interdisciplinary research experience, (2) facilitating dialogue between research students and community settings to disseminate science to the public, and (3) sparking collaborations among researchers who seek to create a way to sustain summer program rotations with grant funding. C1 [Gill, Simone V.; Vessali, Misha; Pratt, Jacob A.; Watts, Samantha] Boston Univ, Dept Occupat Therapy, Boston, MA 02215 USA. [Pratt, Janey S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Raghavan, Preeti] NYU, Langone Med Ctr, Rehabil Med, New York, NY USA. [DeSilva, Jeremy M.] Boston Univ, Anthropol, Boston, MA 02215 USA. RP Gill, SV (reprint author), Boston Univ, Dept Occupat Therapy, Boston, MA 02215 USA. EM simvgill@bu.edu OI Raghavan, Preeti/0000-0002-7852-5005 FU NICHD NIH HHS [K12 HD055931, K12HD055931, R01 HD071978] NR 24 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-8054 EI 1752-8062 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD OCT PY 2015 VL 8 IS 5 BP 611 EP 614 DI 10.1111/cts.12330 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CU6ON UT WOS:000363652100034 PM 26508528 ER PT J AU Stein, TD Alvarez, VE McKee, AC AF Stein, Thor D. Alvarez, Victor E. McKee, Ann C. TI Concussion in Chronic Traumatic Encephalopathy SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Chronic traumatic encephalopathy; Concussion; Head injury ID RESEARCH DIAGNOSTIC-CRITERIA; COLLEGIATE FOOTBALL PLAYERS; SEVERE BRAIN-INJURY; ALZHEIMERS-DISEASE; HEAD-INJURY; APOLIPOPROTEIN-E; SOCCER PLAYERS; PATHOLOGY; FREQUENCY; SPECTRUM AB Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid beta peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. C1 [Stein, Thor D.; McKee, Ann C.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Stein, Thor D.; McKee, Ann C.] Bedford VA Med Ctr, Dept Vet Affairs, Bedford, MA 01730 USA. [Stein, Thor D.; Alvarez, Victor E.; McKee, Ann C.] Boston Univ, Sch Med, Alzheimers Dis & Chron Traumat Encephalopathy Ctr, Boston, MA 02118 USA. [Stein, Thor D.; McKee, Ann C.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Alvarez, Victor E.; McKee, Ann C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Stein, TD (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. EM tdstein@bu.edu OI Stein, Thor/0000-0001-6954-4477 FU Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award; Alzheimer's Association [NIRG-305779]; National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering [U01NS086659-01]; National Institute of Aging Boston University AD Center [P30AG13846, 0572063345-5]; Sports Legacy Institute; Andlinger Foundation; WWE FX We gratefully acknowledge the use of resources and facilities at the Edith Nourse Rogers Memorial Veterans Hospital (Bedford, MA) as well as all the individuals whose participation and contributions made this work possible. This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award; Alzheimer's Association (NIRG-305779); National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering (U01NS086659-01); National Institute of Aging Boston University AD Center (P30AG13846; supplement 0572063345-5); and Sports Legacy Institute. This work was also supported by unrestricted gifts from the Andlinger Foundation and WWE. NR 61 TC 9 Z9 9 U1 8 U2 30 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1531-3433 EI 1534-3081 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD OCT PY 2015 VL 19 IS 10 AR 47 DI 10.1007/s11916-015-0522-z PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CU7ME UT WOS:000363722900001 PM 26260277 ER PT J AU Rollins, BJ Allen, CE Collin, M Jaffe, R Picarsic, JL Rodriguez-Galindo, C AF Rollins, Barrett J. Allen, Carl E. Collin, Matthew Jaffe, Ronald Picarsic, Jennifer L. Rodriguez-Galindo, Carlos TI Dedication SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Rollins, Barrett J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Rollins, Barrett J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Med,Dept Med, Boston, MA 02115 USA. [Allen, Carl E.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Collin, Matthew] Newcastle Univ, Inst Cellular Med, Human Dendrit Cell Lab, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Jaffe, Ronald] Univ Pittsburgh, Sch Med, Dept Pathol, Magee Womens Hosp UPMC, Pittsburgh, PA USA. [Picarsic, Jennifer L.] Univ Pittsburgh, Sch Med, Dept Pathol, Childrens Hosp Pittsburgh UPMC, Pittsburgh, PA USA. [Rodriguez-Galindo, Carlos] Dana Farber Boston Childrens Canc & Blood Disorde, Dept Pediat Oncol, Boston, MA USA. [Rodriguez-Galindo, Carlos] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM barrett_rollins@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2015 VL 29 IS 5 BP XI EP XII DI 10.1016/j.hoc.2015.07.002 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA CU8WC UT WOS:000363823800001 PM 26461160 ER PT J AU Berliner, N Rollins, BJ AF Berliner, Nancy Rollins, Barrett J. TI Congenital and Acquired Disorders of Macrophages and Histiocytes Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Berliner, Nancy] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Rollins, Barrett J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol,Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. RP Berliner, N (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Mid Campus 3 75 Francis St, Boston, MA 02115 USA. EM nberliner@partners.org; barrett_rollins@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2015 VL 29 IS 5 BP XIII EP XV DI 10.1016/j.hoc.2015.07.001 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA CU8WC UT WOS:000363823800002 PM 26461161 ER PT J AU Rollins, BJ AF Rollins, Barrett J. TI Genomic Alterations in Langerhans Cell Histiocytosis SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Langerhans cell histiocytosis; LCH; BRAF; MAP2K1; MEK1 ID ERDHEIM-CHESTER DISEASE; BRAF V600E MUTATION; HIGH PREVALENCE; TUMOR SAMPLES; HUMAN CANCER; B-RAF; ONCOGENE; EXPRESSION; PULMONARY; MELANOMA AB The discovery of recurrent somatic genomic alterations in Langerhans cell histiocytosis (LCH) has led to a new understanding of LCH as a clonal neoplastic disorder. Most of the abnormalities described to date affect the RAS/RAF/MEK/extracellular-signal-regulated kinase (ERK) pathway: more than 50% of LCH cases carry activating mutations in BRAF, whereas another 10% to 28% carry activating mutations of MAP2K1, which encodes MEK1. The pathogenetic importance of these mutations has been confirmed by reports of significant clinical responses to RAF inhibitors. C1 [Rollins, Barrett J.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02215 USA. [Rollins, Barrett J.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02215 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM barrett_rollins@dfci.harvard.edu FU Histiocytosis Association; Team Ippolittle/Deloitte of the Boston Marathon Jimmy Fund Walk; Stichting 1000 Kaarsjes voor Juultje; Say Yes to Education Foundation FX The author has no commercial or financial conflicts of interest to declare. The author's work has been supported by the Histiocytosis Association, Team Ippolittle/Deloitte of the Boston Marathon Jimmy Fund Walk, Stichting 1000 Kaarsjes voor Juultje, the Say Yes to Education Foundation, and Mr George Weiss. NR 55 TC 9 Z9 9 U1 2 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 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2015 VL 29 IS 5 BP 839 EP + DI 10.1016/j.hoc.2015.06.004 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA CU8WC UT WOS:000363823800005 PM 26461146 ER PT J AU Campo, M Berliner, N AF Campo, Meghan Berliner, Nancy TI Hemophagocytic Lymphohistiocytosis in Adults SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Hemophagocytic lymphohistiocytosis; Adults; Acquired hemophagocytic lymphohistiocytosis; Treatment; Diagnosis ID MACROPHAGE ACTIVATION SYNDROME; PROGNOSTIC-FACTORS; CUTANEOUS MANIFESTATIONS; CLINICAL-FEATURES; DIAGNOSIS; ONSET; MUTATIONS; FREQUENCY; CHILDREN; OUTCOMES AB Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal syndrome of pathologic immune dysregulation characterized by clinical signs and symptoms of extreme inflammation. HLH can occur as a genetic or sporadic disorder and, though seen as an inherited condition affecting primarily a pediatric population, can occur at any age and can be encountered in association with a variety of underlying diseases. Clinically, the syndrome, whether genetic or acquired, is characterized by fever, hepatosplenomegaly, cytopenias, and activated macrophages in hematopoietic organs. Therapy centers on suppression of this hyperinflammatory state with cytotoxic, immunosuppressive therapy and treatment of any existing HLH triggers. C1 [Berliner, Nancy] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Campo, Meghan] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Berliner, N (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Mid Campus 3,75 Francis St, Boston, MA 02115 USA. EM nberliner@partners.org NR 32 TC 1 Z9 1 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 OCT PY 2015 VL 29 IS 5 BP 915 EP + DI 10.1016/j.hoc.2015.06.009 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA CU8WC UT WOS:000363823800010 PM 26461151 ER PT J AU Nikiforow, S AF Nikiforow, Sarah TI The Role of Hematopoietic Stem Cell Transplantation in Treatment of Hemophagocytic Lymphohistiocytosis SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Hemophagocytic lymphohistiocytosis; Stem cell transplantation; Alemtuzumab; Chimerism; Treatment ID BONE-MARROW-TRANSPLANTATION; LINKED LYMPHOPROLIFERATIVE DISEASE; PROGNOSTIC-FACTORS; ADULT PATIENTS; CONDITIONING REGIMEN; SINGLE-CENTER; HLH-94 IMMUNOCHEMOTHERAPY; ANTITHYMOCYTE GLOBULINS; CHILDREN; LYMPHOMA AB The role of reduced-intensity allogeneic hematopoietic stem cell transplantation (HSCT) from a variety of donor sources in improving survival for children with familial hemophagocytic lymphohistiocytosis (HLH) is well-documented. The heterogeneity of adult-onset HLH has complicated evaluation of initial therapy and of HSCT as definitive treatment. Therapy for adults with HLH is often individualized, but institutions are now generating algorithms that include HSCT based on growing experience. Consolidation of these data is needed to optimize management of the growing number of adults recognized to have HLH and to achieve dramatic improvements in survival. C1 Dana Farber Canc Inst, Stem Cell Transplantat Program, Cell Manipulat Core Facil, Boston, MA 02215 USA. RP Nikiforow, S (reprint author), Dana Farber Canc Inst, Stem Cell Transplantat Program, Cell Manipulat Core Facil, Dana 168,450 Brookline Ave, Boston, MA 02215 USA. EM Sarah_Nikiforow@DFCI.HARVARD.EDU NR 67 TC 2 Z9 2 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2015 VL 29 IS 5 BP 943 EP + DI 10.1016/j.hoc.2015.06.011 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA CU8WC UT WOS:000363823800012 PM 26461153 ER PT J AU Akrivos, J Ravona-Springer, R Schmeidler, J LeRoith, D Heymann, A Preiss, R Hoffman, H Koifman, K Silverman, JM Beeri, MS AF Akrivos, Jimmy Ravona-Springer, Ramit Schmeidler, James LeRoith, Derek Heymann, Anthony Preiss, Rachel Hoffman, Hadas Koifman, Keren Silverman, Jeremy M. Beeri, Michal Schnaider TI Glycemic control, inflammation, and cognitive function in older patients with type 2 diabetes SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE HbA1c; C-reactive protein; cognitive function; type 2 diabetes; older people ID C-REACTIVE PROTEIN; ACUTE GLUCOSE FLUCTUATIONS; METABOLIC SYNDROME; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; FOLLOW-UP; DECLINE; RISK; PERFORMANCE; INDIVIDUALS AB Objective: Glycated hemoglobin (HbA1c) and C-reactive protein (CRP) have been associated with cognitive impairment independently. However, it is unclear if their combination exacerbates poor cognitive function. We assessed whether long-term glycemic level and glycemic variability modulate the association of systemic inflammation with cognitive function, in a sample of cognitively normal older people with type 2 diabetes. Methods: A retrospective cohort study of 777 randomly selected participants from similar to 11,000 patients in the Maccabi Healthcare Services Diabetes Registry, as part of the Israel Diabetes and Cognitive Decline study. Subjects averaged 18 (+/-9.4) HbA1c measures in the Maccabi Healthcare Services Registry, which were used to calculate long-term glycemic level (HbA1c-mean) and glycemic variability (HbA1c-standard deviation (SD)). Linear regression models assessed the interactions of CRP, a marker of systemic inflammation, with HbA1c-mean and HbA1c-SD on subjects' performance in tests of Memory, Executive Functions, Attention, and Semantic Categorization. Results: Quadratic interactions of CRP with HbA1c-SD approached significance for executive functions and overall cognition. However, after Bonferroni adjustment, none of the interactions of CRP with HbA1c were statistically significant. In partial correlations according to HbA1c-SD tertiles, CRP was weakly correlated in the middle tertile with decreased performance in the domains of semantic categorization (r= -0.166, p=0.011), executive functions (r=-0.136, p=0.038), and overall cognition (r= -0.157, p=0.016). Conclusions: Glycated hemoglobin does not substantially modulate the association of CRP with cognition in a sample of cognitively normal, community dwelling older people with relatively well-managed type 2 diabetes. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Akrivos, Jimmy; Schmeidler, James; Silverman, Jeremy M.; Beeri, Michal Schnaider] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Akrivos, Jimmy; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Ravona-Springer, Ramit; Koifman, Keren; Beeri, Michal Schnaider] Sheba Med Ctr, Joseph Sagol Neurosci Ctr, Ramat Gan, Israel. [LeRoith, Derek] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [LeRoith, Derek] Rambam Med Ctr, Haifa, Israel. [Heymann, Anthony; Preiss, Rachel; Hoffman, Hadas] Maccabi Healthcare Serv, Tel Aviv, Israel. [Beeri, Michal Schnaider] IDC Herzliya, Herzliyya, Israel. RP Akrivos, J (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM Jimmy.Akrivos@mssm.edu FU NIA [R01 AG034087]; Leroy Schecter Foundation; Helen Bader Foundation; Irma T. Hirschl Scholar award; American Federation for Aging Research (AFAR); Alzheimer's Association [NIRG-11-205083] FX This study was supported by NIA grant R01 AG034087 to Dr. Beeri, the Leroy Schecter Foundation, the Helen Bader Foundation, and the Irma T. Hirschl Scholar award to Dr. Beeri, the American Federation for Aging Research (AFAR) Young Investigator award, and the Alzheimer's Association grant NIRG-11-205083 to Dr. Ravona-Springer. NR 30 TC 3 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD OCT PY 2015 VL 30 IS 10 BP 1093 EP 1100 DI 10.1002/gps.4267 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CU7OB UT WOS:000363729700012 PM 25703191 ER PT J AU McCormick, F Nwachukwu, BU Kiriakopoulos, EBS Schairer, WW Provencher, MT Levy, J AF McCormick, Frank Nwachukwu, Benedict U. Kiriakopoulos, Emmanouil B. S. Schairer, William W. Provencher, Matthew T. Levy, Jonathan TI In-hospital mortality risk for total shoulder arthroplasty: A comprehensive review of the medicare database from 2005 to 2011 SO INTERNATIONAL JOURNAL OF SHOULDER SURGERY LA English DT Article DE Complications; in-hospital mortality; Medicare; reverse total shoulder replacement; total shoulder replacement ID TOTAL JOINT ARTHROPLASTY; TOTAL KNEE ARTHROPLASTY; ELECTIVE TOTAL HIP; 90-DAY MORTALITY; COMPLICATIONS; EPIDEMIOLOGY; DEMOGRAPHICS; MORBIDITY; SURGERY; TRENDS AB Introduction: The in-hospital mortality rate after total shoulder arthroplasty (TSA) is unknown. The purpose of this study is to quantify the in-patient mortality rates and associated demographic risk factors for patients undergoing a TSA from 2005 to 2011 using a comprehensive Medicare registry database. Materials and Methods: We conducted a retrospective review of the Medicare database within the PearlDiver database. The PearlDiver database is a publicly available Health Insurance Portability and Accountability Act-compliant national database that captures 100% of the Medicare hospital data for TSA between 2005 and 2011. Using International Classification of Diseases, Ninth Revision codes for TSA we identified a dataset of patients undergoing TSA as well as a subset of those for whom there was a death discharge (i. e., in-patient death). Risk for this outcome was further quantified by age, gender and year. Linear regression was performed to identify risk factors for the primary outcome. Results: A total of 101,323 patients underwent 125,813 TSAs between 2005 and 2011. There were 113 in-patient mortalities during this period. Thus the incidence of death was 0.09%. Increasing age was a significant risk factor for mortality (P = 0.03). Gender and year of procedure were not significant risk factors for mortality. Conclusion: The incidence of in-patient mortality for Medicare patients undergoing TSA between 2005 and 2011 was < 1 in 1000 surgeries. Increased age is a significant predictor of mortality. Level 4: Retrospective analysis C1 [McCormick, Frank; Kiriakopoulos, Emmanouil B. S.; Levy, Jonathan] Holy Cross Hosp, Holy Cross Orthoped Inst, Ft Lauderdale, FL USA. [Nwachukwu, Benedict U.; Schairer, William W.] Hosp Special Surg, Dept Orthoped Surg, New York, NY 10021 USA. [Provencher, Matthew T.] Massachusetts Gen Hosp, Dept Sports Med, Boston, MA 02114 USA. RP McCormick, F (reprint author), 5597 North Dixie Highway, Ft Lauderdale, FL 33334 USA. EM drfrankmccormick@yahoo.com OI Levy, Jonathan/0000-0002-1699-0841; Schairer, William/0000-0001-6162-9329 NR 18 TC 0 Z9 0 U1 1 U2 1 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0973-6042 J9 INT J SHOULDER SURG JI Int. J. Shoulder Surg. PD OCT-DEC PY 2015 VL 9 IS 4 BP 110 EP 113 DI 10.4103/0973-6042.167938 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CU9KX UT WOS:000363864500002 PM 26622126 ER PT J AU Sandhu, H Vavvas, D AF Sandhu, Harpal Vavvas, Demetrios TI Bilateral tractional retinal detachment in a patient with hemolytic-uremic syndrome SO JOURNAL OF AAPOS LA English DT Article ID OCULAR INVOLVEMENT; THROMBOTIC MICROANGIOPATHY; RETINOPATHY AB Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by hemolytic anemia, acute kidney injury, and thrombocytopenia. Ophthalmic manifestations of HUS range from mild, including scattered intraretinal hemorrhages, to severe, including a Purtscher-like retinopathy and iris and optic disk neovascularization (NVD). We report the case of a 23-month-old girl with severe HUS who presented with bilateral dense vitreous hemorrhage. During vitrectomy, optic disk neovascularization and funnel-shaped, tractional detachments of both retinas were observed. To our knowledge, this is the first reported case of tractional retinal detachment in the context of HUS. C1 [Sandhu, Harpal] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Sch Med, Philadelphia, PA 19104 USA. [Vavvas, Demetrios] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Sandhu, H (reprint author), Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Sch Med, 51 N 39th St, Philadelphia, PA 19104 USA. EM harpal.sandhu@uphs.upenn.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 EI 1528-3933 J9 J AAPOS JI J. AAPOS PD OCT PY 2015 VL 19 IS 5 BP 484 EP 486 DI 10.1016/j.jaapos.2015.05.017 PG 3 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA CU7ID UT WOS:000363709000025 PM 26486040 ER PT J AU Roden-Reynolds, DC Walker, MH Wasserman, CR Dean, JC AF Roden-Reynolds, Devin C. Walker, Megan H. Wasserman, Camille R. Dean, Jesse C. TI Hip proprioceptive feedback influences the control of mediolateral stability during human walking SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE biomechanics; locomotion; sensory feedback; vibration ID LEG MUSCLE VIBRATION; CENTER-OF-MASS; LATERAL BALANCE; FOOT PLACEMENT; FRONTAL PLANE; DYNAMIC STABILITY; TENDON VIBRATION; TREADMILL WALKING; HUMAN STANCE; STEP WIDTH AB Active control of the mediolateral location of the feet is an important component of a stable bipedal walking pattern, although the roles of sensory feedback in this process are unclear. In the present experiments, we tested whether hip abductor proprioception influenced the control of mediolateral gait motion. Participants performed a series of quiet standing and treadmill walking trials. In some trials, 80-Hz vibration was applied intermittently over the right gluteus medius (GM) to evoke artificial proprioceptive feedback. During walking, the GM was vibrated during either right leg stance (to elicit a perception that the pelvis was closer mediolaterally to the stance foot) or swing (to elicit a perception that the swing leg was more adducted). Vibration during quiet standing evoked leftward sway in most participants (13 of 16), as expected from its predicted perceptual effects. Across the 13 participants sensitive to vibration, stance phase vibration caused the contralateral leg to be placed significantly closer to the midline (by similar to 2 mm) at the end of the ongoing step. In contrast, swing phase vibration caused the vibrated leg to be placed significantly farther mediolaterally from the midline (by similar to 2 mm), whereas the pelvis was held closer to the stance foot (by similar to 1 mm). The estimated mediolateral margin of stability was thus decreased by stance phase vibration but increased by swing phase vibration. Although the observed effects of vibration were small, they were consistent with humans monitoring hip proprioceptive feedback while walking to maintain stable mediolateral gait motion. C1 [Roden-Reynolds, Devin C.; Walker, Megan H.; Wasserman, Camille R.; Dean, Jesse C.] Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA. [Dean, Jesse C.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Dean, JC (reprint author), Med Univ S Carolina, 77 President St MSC700, Charleston, SC 29425 USA. EM deaje@musc.edu OI Dean, Jesse/0000-0003-2034-4217 FU Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development Service [1IK2RX000750-01A1] FX This study was partially supported by the Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development Service, through Grant No. 1IK2RX000750-01A1. NR 58 TC 3 Z9 3 U1 7 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT 1 PY 2015 VL 114 IS 4 BP 2220 EP 2229 DI 10.1152/jn.00551.2015 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA CU5CC UT WOS:000363548300015 PM 26289467 ER PT J AU Cragan, JD Young, BA Correa, A AF Cragan, Janet D. Young, Bessie A. Correa, Adolfo TI Renin-Angiotensin System Blocker Fetopathy SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID EARLY-PREGNANCY; MALFORMATIONS; INHIBITION; EXPOSURE C1 [Cragan, Janet D.] Ctr Dis Control & Prevent, Div Birth Defects & Dev Disabil, Atlanta, GA USA. [Young, Bessie A.] Univ Washington, Dept Med, Div Nephrol, Vet Affairs Puget Sound,Kidney Res Inst, Seattle, WA 98195 USA. [Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA. RP Correa, A (reprint author), Univ Mississippi, Med Ctr, Dept Med, 2500 North State St, Jackson, MS 39216 USA. EM acorrea@umc.edu FU Intramural CDC HHS [CC999999]; NCCIH NIH HHS [U01 AT006239, 1U01AT006239-01]; NHLBI NIH HHS [HHSN268201300049C, HHSN268201300046C]; NIDDK NIH HHS [R01 DK102134, 1R01DK102134-01]; NIMHD NIH HHS [P60MD002249-01, P60 MD002249]; PHS HHS [HHSN268201300047C, HHSN268201300049C, HHSN268201300046C] NR 18 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2015 VL 167 IS 4 BP 792 EP 794 DI 10.1016/j.jpeds.2015.07.024 PG 3 WC Pediatrics SC Pediatrics GA CU5BE UT WOS:000363545800004 PM 26254838 ER PT J AU Kim, Y Elmenhorst, D Weisshaupt, A Wedekind, F Kroll, T Mccarley, RW Strecker, RE Bauer, A AF Kim, Youngsoo Elmenhorst, David Weisshaupt, Angela Wedekind, Franziska Kroll, Tina Mccarley, Robert W. Strecker, Robert E. Bauer, Andreas TI Chronic sleep restriction induces long-lasting changes in adenosine and noradrenaline receptor density in the rat brain SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE [H-3]-ZM 241385; [H-3]-DPCPX; basal forebrain; [H-3-1]-DHA; receptor autoradiography ID POSITRON-EMISSION-TOMOGRAPHY; MESSENGER-RNA; MATHEMATICAL-MODEL; DOSE-RESPONSE; DEPRIVATION; A(1); WAKEFULNESS; PERFORMANCE; AROUSAL; SYSTEM AB Although chronic sleep restriction frequently produces long-lasting behavioural and physiological impairments in humans, the underlying neural mechanisms are unknown. Here we used a rat model of chronic sleep restriction to investigate the role of brain adenosine and noradrenaline systems, known to regulate sleep and wakefulness, respectively. The density of adenosine A1 and A2a receptors and beta-adrenergic receptors before, during and following 5 days of sleep restriction was assessed with autoradiography. Rats (n = 48) were sleep-deprived for 18 h day(-1) for 5 consecutive days (SR1-SR5), followed by 3 unrestricted recovery sleep days (R1-R3). Brains were collected at the beginning of the light period, which was immediately after the end of sleep deprivation on sleep restriction days. Chronic sleep restriction increased adenosine Al receptor density significantly in nine of the 13 brain areas analysed with elevations also observed on R3 (-18 to +32%). In contrast, chronic sleep restriction reduced adenosine A2a receptor density significantly in one of the three brain areas analysed (olfactory tubercle which declined 26-31% from SR1 to R1). A decrease in fi-adrenergic receptors density was seen in substantia innominata and ventral pallidunn which remained reduced on R3, but no changes were found in the anterior cingulate cortex. These data suggest that chronic sleep restriction can induce long-term changes in the brain adenosine and noradrenaline receptors, which may underlie the long-lasting neurocognitive impairments observed in chronic sleep restriction. C1 [Kim, Youngsoo; Elmenhorst, David; Mccarley, Robert W.; Strecker, Robert E.] VA Boston Healthcare Syst, Res Serv, Dept Psychiat, Brockton, MA USA. [Kim, Youngsoo; Elmenhorst, David; Mccarley, Robert W.; Strecker, Robert E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Elmenhorst, David; Weisshaupt, Angela; Wedekind, Franziska; Kroll, Tina; Bauer, Andreas] Forschungszentrum Julich, Inst Neurosci & Med INM2, D-52425 Julich, Germany. [Bauer, Andreas] Univ Dusseldorf, Dept Neurol, Dusseldorf, Germany. RP Kim, Y (reprint author), Univ Michigan, Dept Psychol, 1012 East Hall,530 Church St, Ann Arbor, MI 48109 USA. EM ysookim@umich.edu; d.elmenhorst@fz-juelich.de RI Bauer, Andreas/H-8759-2013; OI Bauer, Andreas/0000-0002-0117-3793; Wedekind, Franziska/0000-0003-1198-7480; Elmenhorst, David/0000-0001-6137-416X FU Department of Veterans Affairs Medical Research Service Award [HL060292, MH039683, HL095491, NHLBI-T32 HL07901] FX We thank Maxine Dibue, Sabine Wilms, Yunren Bolortuya and Patrick Schelenz for technical assistance and Dr Radhika Basheer for helpful discussions. This research was supported by the Department of Veterans Affairs Medical Research Service Award (to RES), HL060292 (to RES and RWM), MH039683 and HL095491 (to RWM), NHLBI-T32 HL07901 (to YK). NR 38 TC 3 Z9 3 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD OCT PY 2015 VL 24 IS 5 BP 549 EP 558 DI 10.1111/jsr.12300 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CU9ST UT WOS:000363886100011 PM 25900125 ER PT J AU Cooper, Z Mitchell, SL Lipsitz, S Harris, MB Ayanian, JZ Bernacki, RE Jha, AK AF Cooper, Zara Mitchell, Susan L. Lipsitz, Stuart Harris, Mitchel B. Ayanian, John Z. Bernacki, Rachelle E. Jha, Ashish K. TI Mortality and Readmission After Cervical Fracture from a Fall in Older Adults: Comparison with Hip Fracture Using National Medicare Data SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cervical fracture; mortality; readmission ID TRAUMA; PERFORMANCE; POPULATION; DISABILITY; INJURIES; OUTCOMES; FAILURE; SERVICE; CARE; AGE AB ObjectivesTo examine the prevalence of cervical spine fractures after falls in older Americans, to show changes in recent years, and to compare 12-month outcomes between individuals with cervical and hip fracture after falls. DesignRetrospective study of Medicare data from 2007 to 2011. SettingAcute care hospitals. ParticipantsIndividuals aged 65 and older with cervical or hip fracture after a fall. MeasurementsCervical fracture rate, 12-month mortality, and readmission rate after injury. ResultsRates of cervical fracture increased from 4.6 per 10,000 in 2007 to 5.3 per 10,000 in 2011; rates of hip fracture decreased from 77.3 per 10,000 in 2007 to 63.5 per 10,000 in 2011. Participants with cervical fracture with and without spinal cord injury (SCI) were more likely than those with hip fracture to receive treatment at large hospitals (59.4% and 54.1% vs 28.1%, P < .001), teaching hospitals (49.3% and 40.0% vs 13.4%, P < .001), and regional trauma centers (46.3% and 38.5% vs 13.0%, P < .001). Participants with cervical fracture without (24.7%) and with SCI (41.7%) had greater risk-adjusted mortality at 1 year than those with hip fracture (22.7%) (P < .001). By 1 year, 73.4% of participants with cervical fracture with and 59.5% without SCI and 59.3% of those with hip fracture had died or were readmitted to the hospital (P < .001). ConclusionCervical spinal fractures occur in one of every 2,000 Medicare beneficiaries annually and appear to be increasing over time. Participants with cervical fracture had greater mortality than those with hip fracture. Given the increasing prevalence and the poor outcomes in this population, hospitals need to develop processes to improve care for these vulnerable individuals. C1 [Cooper, Zara] Brigham & Womens Hosp, Div Trauma Burns & Surg Crit Care, Boston, MA 02115 USA. [Cooper, Zara; Lipsitz, Stuart] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Cooper, Zara; Mitchell, Susan L.; Harris, Mitchel B.] Harvard Univ, Med Sch Med, Boston, MA 02115 USA. [Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Mitchell, Susan L.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Lipsitz, Stuart; Bernacki, Rachelle E.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Harris, Mitchel B.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Ayanian, John Z.] Univ Michigan, Div Gen Med, Ann Arbor, MI USA. [Ayanian, John Z.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Bernacki, Rachelle E.] Ariadne Labs, Boston, MA USA. [Jha, Ashish K.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Cooper, Z (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM zcooper@partners.org FU NIA NIH HHS [K24 AG033640, K24AG033640, 1R03AG042361-01, R03 AG042361] NR 28 TC 3 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2015 VL 63 IS 10 BP 2036 EP 2042 DI 10.1111/jgs.13670 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CU8PQ UT WOS:000363805800009 PM 26456855 ER PT J AU Naples, JG Marcum, ZA Perera, S Gray, SL Newman, AB Simonsick, EM Yaffe, K Shorr, RI Hanlon, JT AF Naples, Jennifer G. Marcum, Zachary A. Perera, Subashan Gray, Shelly L. Newman, Anne B. Simonsick, Eleanor M. Yaffe, Kristine Shorr, Ronald I. Hanlon, Joseph T. CA Hlth Aging Body Composition Study TI Concordance Between Anticholinergic Burden Scales SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cholinergic antagonists; aged; drug use ID OLDER-PEOPLE; DRUG BURDEN; BODY-COMPOSITION; ASSOCIATIONS; HEALTH; INDEX; MEDICATIONS; DECLINE; ELDERS AB ObjectivesTo evaluate concordance of five commonly used anticholinergic scales. DesignCross-sectional secondary analysis. SettingPittsburgh, Pennsylvania, and Memphis, Tennessee. ParticipantsCommunity-dwelling adults aged 70 to 79 with baseline medication data from the Health, Aging, and Body Composition Study (N = 3,055). MeasurementsAny anticholinergic use, weighted scores, and total standardized daily dosage were calculated using five anticholinergic measures (Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), Drug Burden Index anticholinergic component (DBI-ACh), and Summated Anticholinergic Medications Scale (SAMS)). Concordance was evaluated using kappa statistics and Spearman rank correlations. ResultsAny anticholinergic use in rank order was 51% for the ACB, 43% for the ADS, 29% for the DBI-ACh, 23% for the ARS, and 16% for the SAMS. Kappa statistics for all pairwise use comparisons ranged from 0.33 to 0.68. Similarly, concordance as measured using weighted kappa statistics ranged from 0.54 to 0.70 for the three scales not incorporating dosage (ADS, ARS, ACB). Spearman rank correlation between the DBI-ACh and SAMS was 0.50. ConclusionOnly low to moderate concordance was found between the five anticholinergic scales. Future research is needed to examine how these differences in measurement affect their predictive validity with respect to clinically relevant outcomes, such as cognitive impairment. C1 [Naples, Jennifer G.; Perera, Subashan; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr, Pittsburgh, PA 15213 USA. [Naples, Jennifer G.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Naples, Jennifer G.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. [Naples, Jennifer G.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Marcum, Zachary A.; Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Perera, Subashan] Univ Pittsburgh, Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 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 USA. [Shorr, Ronald I.] Malcolm Randall Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA. RP Naples, JG (reprint author), Univ Pittsburgh, Dept Geriatr Med, Kaufmann Med Bldg Suite 500,3471 Fifth Ave, Pittsburgh, PA 15213 USA. EM jgn13@pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU Intramural NIH HHS; NIA NIH HHS [R01 AG037451, K07 AG033174, K07-AG033174, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30 AG024827, P30-AG024827, R01-AG037451, T32 AG021885, T32-AG021885]; NINR NIH HHS [NR012459, R01 NR012459] NR 22 TC 6 Z9 7 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2015 VL 63 IS 10 BP 2120 EP 2124 DI 10.1111/jgs.13647 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CU8PQ UT WOS:000363805800021 PM 26480974 ER PT J AU Olesen, R Vigano, S Rasmussen, TA Sogaard, OS Ouyang, ZY Buzon, M Bashirova, A Carrington, M Palmer, S Brinkmann, CR Yu, XG Ostergaard, L Tolstrup, M Lichterfeld, M AF Olesen, Rikke Vigano, Selena Rasmussen, Thomas A. Sogaard, Ole S. Ouyang, Zhengyu Buzon, Maria Bashirova, Arman Carrington, Mary Palmer, Sarah Brinkmann, Christel R. Yu, Xu G. Ostergaard, Lars Tolstrup, Martin Lichterfeld, Mathias TI Innate Immune Activity Correlates with CD4 T Cell-Associated HIV-1 DNA Decline during Latency-Reversing Treatment with Panobinostat SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-C VIRUS; HISTONE DEACETYLASE INHIBITORS; IL28B GENOTYPE; LYMPHOCYTE-ACTIVATION; TYPE-1 REPLICATION; CYTOLYTIC ACTIVITY; ELITE CONTROLLERS; INTERFERON-ALPHA; I INTERFERON; SET-POINT AB The pharmaceutical reactivation of dormant HIV-1 proviruses by histone deacetylase inhibitors (HDACi) represents a possible strategy to reduce the reservoir of HIV-1-infected cells in individuals treated with suppressive combination antiretroviral therapy (cART). However, the effects of such latency-reversing agents on the viral reservoir size are likely to be influenced by host immune responses. Here, we analyzed the immune factors associated with changes in proviral HIV-1 DNA levels during treatment with the potent HDACi panobinostat in a human clinical trial involving 15 cART-treated HIV-1-infected patients. We observed that the magnitude, breadth, and cytokine secretion profile of HIV-1-specific CD8 T cell responses were unrelated to changes in HIV-1 DNA levels in CD4 T cells during panobinostat treatment. In contrast, the proportions of CD3(-) CD56(+) total NK cells and CD16(+) CD56(dim) NK cells were inversely correlated with HIV-1 DNA levels throughout the study, and changes in HIV-1 DNA levels during panobinostat treatment were negatively associated with the corresponding changes in CD69(+) NK cells. Decreasing levels of HIV-1 DNA during latency-reversing treatment were also related to the proportions of plasmacytoid dendritic cells, to distinct expression patterns of interferon-stimulated genes, and to the expression of the IL28B CC genotype. Together, these data suggest that innate immune activity can critically modulate the effects of latency-reversing agents on the viral reservoir and may represent a target for future immunotherapeutic interventions in HIV-1 eradication studies. IMPORTANCE Currently available antiretroviral drugs are highly effective in suppressing HIV-1 replication, but the virus persists, despite treatment, in a latent form that does not actively express HIV-1 gene products. One approach to eliminate these cells, colloquially termed the "shock-and-kill" strategy, focuses on the use of latency-reversing agents that induce active viral gene expression in latently infected cells, followed by immune-mediated killing. Panobinostat, a histone deacetylase inhibitor, demonstrated potent activities in reversing HIV-1 latency in a recent pilot clinical trial and reduced HIV-1 DNA levels in a subset of patients. Interestingly, we found that innate immune factors, such as natural killer cells, plasmacytoid dendritic cells, and the expression patterns of interferon-stimulated genes, were most closely linked to a decline in the HIV-1 DNA level during treatment with panobinostat. These data suggest that innate immune activity may play an important role in reducing the residual reservoir of HIV-1-infected cells. C1 [Olesen, Rikke; Rasmussen, Thomas A.; Sogaard, Ole S.; Brinkmann, Christel R.; Ostergaard, Lars; Tolstrup, Martin] Aarhus Univ Hosp, Div Infect Dis, DK-8000 Aarhus, Denmark. [Vigano, Selena; Ouyang, Zhengyu; Buzon, Maria; Yu, Xu G.; Lichterfeld, Mathias] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA. [Vigano, Selena; Ouyang, Zhengyu; Buzon, Maria; Yu, Xu G.; Lichterfeld, Mathias] Harvard, Cambridge, MA USA. [Vigano, Selena; Buzon, Maria; Yu, Xu G.; Lichterfeld, Mathias] Harvard Univ, Sch Med, Boston, MA USA. [Bashirova, Arman; Carrington, Mary] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA. [Palmer, Sarah] Univ Sydney, Westmead Millennium Inst Med Res, Sydney, NSW 2006, Australia. [Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Lichterfeld, Mathias] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Lichterfeld, M (reprint author), MIT, Ragon Inst MGH, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mlichterfeld@mgh.harvard.edu RI Sogaard, Ole/P-6058-2016; OI Buzon, Maria Jose/0000-0003-4427-9413; Rasmussen, Thomas Aagaard/0000-0001-5354-2442; Olesen, Rikke/0000-0002-5157-080X FU Danish Strategic Research Council [0603-00521B]; American Foundation for AIDS Research [108302-51-RGRL]; Clinical Scientist Development Award from the Doris Duke Charitable Foundation [2009034]; Danish Research Council [12-133887]; Lundbeck Foundation [R126-2012-12588] FX This work was supported by The Danish Strategic Research Council (grant 0603-00521B) and the American Foundation for AIDS Research (grant 108302-51-RGRL). M.L. is a recipient of the Clinical Scientist Development Award from the Doris Duke Charitable Foundation (grant number 2009034). O.S.S. is supported by a grant from the Danish Research Council (grant 12-133887) and a grant from the Lundbeck Foundation (grant R126-2012-12588). NR 64 TC 16 Z9 16 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 2015 VL 89 IS 20 BP 10176 EP 10189 DI 10.1128/JVI.01484-15 PG 14 WC Virology SC Virology GA CU3ZG UT WOS:000363464700004 PM 26223643 ER PT J AU Hu, JK Crampton, JC Cupo, A Ketas, T van Gils, MJ Sliepen, K de Taeye, SW Sok, D Ozorowski, G Deresa, I Stanfield, R Ward, AB Burton, DR Klasse, PJ Sanders, RW Moore, JP Crotty, S AF Hu, Joyce K. Crampton, Jordan C. Cupo, Albert Ketas, Thomas van Gils, Marit J. Sliepen, Kwinten de Taeye, Steven W. Sok, Devin Ozorowski, Gabriel Deresa, Isaiah Stanfield, Robyn Ward, Andrew B. Burton, Dennis R. Klasse, Per Johan Sanders, Rogier W. Moore, John P. Crotty, Shane TI Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; FOLLICULAR HELPER-CELL; CENTER B-CELLS; BROADLY NEUTRALIZING ANTIBODIES; MUCOSAL SHIV CHALLENGE; GERMINAL CENTER; MONOCLONAL-ANTIBODIES; GP41-GP120 INTERFACE; GLYCOPROTEIN TRIMERS; IMMUNOGLOBULIN GENES AB Generating neutralizing antibodies (nAbs) is a major goal of many current HIV-1 vaccine efforts. To be of practical value, these nAbs must be both potent and cross-reactive in order to be capable of preventing the transmission of the highly diverse and generally neutralization resistant (Tier-2) HIV-1 strains that are in circulation. The HIV-1 envelope glycoprotein (Env) spike is the only target for nAbs. To explore whether Tier-2 nAbs can be induced by Env proteins, we immunized conventional mice with soluble BG505 SOSIP. 664 trimers that mimic the native Env spike. Here, we report that it is extremely difficult for murine B cells to recognize the Env epitopes necessary for inducing Tier-2 nAbs. Thus, while trimer-immunized mice raised Env-binding IgG Abs and had high-quality T follicular helper (Tfh) cell and germinal center (GC) responses, they did not make BG505.T332N nAbs. Epitope mapping studies showed that Ab responses in mice were specific to areas near the base of the soluble trimer. These areas are not well shielded by glycans and likely are occluded on virions, which is consistent with the lack of BG505.T332N nAbs. These data inform immunogen design and suggest that it is useful to obscure nonneutralizing epitopes presented on the base of soluble Env trimers and that the glycan shield of well-formed HIV Env trimers is virtually impenetrable for murine B cell receptors (BCRs). IMPORTANCE Human HIV vaccine efficacy trials have not generated meaningful neutralizing antibodies to circulating HIV strains. One possible hindrance has been the lack of immunogens that properly mimic the native conformation of the HIV envelope trimer protein. Here, we tested the first generation of soluble, native-like envelope trimer immunogens in a conventional mouse model. We attempted to generate neutralizing antibodies to neutralization-resistant circulating HIV strains. Various vaccine strategies failed to induce neutralizing antibodies to a neutralization-resistant HIV strain. Further analysis revealed that mouse antibodies targeted areas near the bottom of the soluble envelope trimers. These areas are not easily accessible on the HIV virion due to occlusion by the viral membrane and may have resulted from an absence of glycan shielding. Our results suggest that obscuring the bottom of soluble envelope trimers is a useful strategy to reduce antibody responses to epitopes that are not useful for virus neutralization. C1 [Hu, Joyce K.; Crampton, Jordan C.; Deresa, Isaiah; Crotty, Shane] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA. [Hu, Joyce K.; Crampton, Jordan C.; Sok, Devin; Ozorowski, Gabriel; Deresa, Isaiah; Ward, Andrew B.; Burton, Dennis R.; Crotty, Shane] Ctr HIV 1 AIDS Vaccine Immunol & Immunogen Discov, La Jolla, CA USA. [Cupo, Albert; Ketas, Thomas; Klasse, Per Johan; Sanders, Rogier W.; Moore, John P.] Cornell Univ, Dept Microbiol & Immunol, Weill Med Coll, New York, NY 10021 USA. [van Gils, Marit J.; Sliepen, Kwinten; de Taeye, Steven W.; Sanders, Rogier W.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands. [Ozorowski, Gabriel; Ward, Andrew B.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Sok, Devin; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Sok, Devin; Burton, Dennis R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Sok, Devin; Burton, Dennis R.] Harvard Univ, Boston, MA 02115 USA. [Stanfield, Robyn] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. RP Crotty, S (reprint author), La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA. EM shane@lji.org RI Ward, Andrew/F-9203-2014 OI Ward, Andrew/0000-0001-7153-3769 FU Scripps CHAVI-ID [UM1-Al100663]; IAVI; U.S. AID; Bill & Melinda Gates Foundation FX This work was supported by Scripps CHAVI-ID (UM1-Al100663). This work was partially funded by IAVI with the generous support of U.S. AID and the Bill & Melinda Gates Foundation; a full list of IAVI donors is available at www.iavi.org. NR 90 TC 16 Z9 16 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 2015 VL 89 IS 20 BP 10383 EP 10398 DI 10.1128/JVI.01653-15 PG 16 WC Virology SC Virology GA CU3ZG UT WOS:000363464700020 PM 26246566 ER PT J AU Beckett, MK Elliott, MN Haviland, AM Burkhart, Q Gaillot, S Montfort, D Saliba, D AF Beckett, Megan K. Elliott, Marc N. Haviland, Amelia M. Burkhart, Q. Gaillot, Sarah Montfort, Daisy Saliba, Debra TI Living Alone and Patient Care Experiences: The Role of Gender in a National Sample of Medicare Beneficiaries SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Living arrangements; Patient experience; Gender; Medicare ID CAHPS(R) HOSPITAL SURVEY; PSYCHOMETRIC PROPERTIES; CONSUMER ASSESSMENT; TRANSITIONAL CARE; ELDERLY PERSONS; MARITAL-STATUS; HEART-FAILURE; MANAGED CARE; HEALTH PLANS; OLDER-ADULTS AB Seniors who live alone are a large, growing population with poorer health outcomes. We examine the little-studied health care experiences and immunizations of older adults who live alone. We use regression-based case-mix adjustment to compare immunizations and health care experiences of 325,649 adults aged 65 and older who lived alone to those who did not, overall and by gender and health status, using nationally representative data from the Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS) surveys. Outcomes were five global care ratings (health plan, drug plan, doctor, specialists, all care), six composite care measures (getting needed care, getting care quickly, doctor communication, customer service, getting needed drugs, getting information from drug plan), and two immunization measures (influenza, pneumonia). About 30.3% of respondents lived alone. Women, older beneficiaries, and low income (Medicaid eligible) beneficiaries reported living alone at substantially higher rates than their counterparts. Care experiences for 8 of the 13 measures were significantly worse for those who lived alone than for others. The association differed significantly in magnitude by gender for 10 measures, with larger average differences for men. The largest disadvantages for those living alone were for immunization measures (eg, influenza -6 percentage points, for men living alone vs other men). The disadvantages of living alone were not consistently greater for those in worse health. Living alone is associated with worse care experiences and immunization, especially for men. Health plans should target quality improvement and outreach efforts to beneficiaries who live alone, especially men. C1 [Beckett, Megan K.; Elliott, Marc N.; Haviland, Amelia M.; Burkhart, Q.; Montfort, Daisy; Saliba, Debra] RAND Corp, Santa Monica, CA 90401 USA. [Haviland, Amelia M.] Carnegie Mellon Univ, H John Heinz III Coll Publ Policy & Management, Pittsburgh, PA 15213 USA. [Gaillot, Sarah] Ctr Medicare & Medicaid Serv, Div Consumer Assessment & Plan Performance, Baltimore, MD USA. [Saliba, Debra] Ctr Geriatr Res Educ & Clin, US Dept Vet Affairs, Los Angeles, CA USA. [Saliba, Debra] Univ Calif Los Angeles, Dept Med, Borun Ctr, Los Angeles, CA 90024 USA. RP Elliott, MN (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM elliott@rand.org FU Centers for Medicare and Medicare Services [HHSM-500-2005-00028I] FX This work was supported by the Centers for Medicare and Medicare Services (contract HHSM-500-2005-00028I awarded to RAND). NR 34 TC 1 Z9 1 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 2015 VL 70 IS 10 BP 1242 EP 1247 DI 10.1093/gerona/glv037 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CU4FD UT WOS:000363481600009 PM 25869525 ER PT J AU van Steenoven, I Aarsland, D Weintraub, D AF van Steenoven, Inger Aarsland, Dag Weintraub, Daniel TI Reply to letter to the editor "Independent application of MoCA/MMSE conversion' by Armstrong et al. SO MOVEMENT DISORDERS LA English DT Letter C1 [van Steenoven, Inger] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, NL-1081 HV Amsterdam, Netherlands. [van Steenoven, Inger] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, NL-1081 HV Amsterdam, Netherlands. [Aarsland, Dag] Karolinska Inst, Div Clin Geriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden. [Aarsland, Dag] Stavanger Univ Hosp, Ctr Age Related Med, Stavanger, Norway. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP van Steenoven, I (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Boelelaan 1118, NL-1081 HV Amsterdam, Netherlands. EM i.vansteenoven@vumc.nl OI Aarsland, Dag/0000-0001-6314-216X NR 2 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT PY 2015 VL 30 IS 12 BP 1711 EP 1711 DI 10.1002/mds.26367 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA CU2GU UT WOS:000363342800022 PM 26228296 ER PT J AU Al-Rashid, M Ramkumar, DB Raskin, K Schwab, J Hornicek, FJ Lozano-Calderon, SA AF Al-Rashid, Mamun Ramkumar, Dipak B. Raskin, Kevin Schwab, Joseph Hornicek, Francis J. Lozano-Calderon, Santiago A. TI Paget Disease of Bone SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article DE Paget disease of bone; Paget; Bone turnover; Bisphosphonates; SQSTM1; Arthroplasty in Paget disease; Fracture fixation of pagetic bone; Paget sarcoma ID HIP-ARTHROPLASTY; TOTAL KNEE; DOUBLE-BLIND; MANAGEMENT; EPIDEMIOLOGY; ETIDRONATE; SQSTM1; VIRUS; MULTICENTER; RISEDRONATE AB The current understanding of Paget disease of bone (PDB) has vastly changed since Paget described the first case in 1877. Medical management of this condition remains the mainstay of treatment. Surgical intervention is usually only used in fractures through pagetic bone, need for realignment to correct deformity in major long bones, prophylactic treatment of impending fractures, joint arthroplasty in severe arthritis, or spinal decompression in cases of bony compression of neural elements. Advances in surgical technique have allowed early return to function and mobilization. Despite medical intervention, a small subset of patients with PDB develops Paget sarcoma. C1 [Al-Rashid, Mamun; Raskin, Kevin; Schwab, Joseph; Hornicek, Francis J.; Lozano-Calderon, Santiago A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv,Dept Orthopaed Surg, Boston, MA 02114 USA. [Al-Rashid, Mamun; Lozano-Calderon, Santiago A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Orthopaed Oncol Serv,Dept Orthopaed Surg, Boston, MA 02215 USA. [Ramkumar, Dipak B.] Dartmouth Hitchcock Med Ctr, Dept Orthopaed Surg, Lebanon, NH 03766 USA. RP Lozano-Calderon, SA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Oncol Serv, 55 Fruit St, Boston, MA 02114 USA. EM slozanocalderon@mgh.harvard.edu NR 56 TC 3 Z9 3 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 0030-5898 EI 1558-1373 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD OCT PY 2015 VL 46 IS 4 BP 577 EP + DI 10.1016/j.ocl.2015.06.008 PG 11 WC Orthopedics SC Orthopedics GA CU7IC UT WOS:000363708900019 PM 26410646 ER PT J AU Tanpowpong, P Broder-Fingert, S Katz, AJ Camargo, CA AF Tanpowpong, Pornthep Broder-Fingert, Sarabeth Katz, Aubrey J. Camargo, Carlos A., Jr. TI Features of children with positive celiac serology and type 1 diabetes mellitus SO PEDIATRICS INTERNATIONAL LA English DT Article DE child; enteropathy; esophagitis; gluten; reflux ID DISEASE AB Prior studies have reported disparate clinical presentations between children with celiac disease and type 1 diabetes mellitus and those with celiac disease alone. Studies focusing on differences in endoscopic and histopathological findings, however, are limited. We reviewed children aged 2-18 years, presenting for an initial evaluation between January 2000 and December 2010. Data on medical history, serologic markers, upper endoscopy, and histopathology were collected. Only the children with positive celiac serology who had upper endoscopy performed within 3months of the initial visit were included. We identified 294 children who fulfilled the criteria, 21 of whom had diagnosed type 1 diabetes mellitus. Diabetic children were more likely to have absence of gastrointestinal symptoms. Erythematous duodenal and esophageal mucosa on endoscopy, and histopathology suggestive of reflux esophagitis were more common in the diabetes group. Diabetic children with positive celiac serology had different histopathological features as compared with their non-diabetic counterparts. C1 [Tanpowpong, Pornthep] Mahidol Univ, Ramathibodi Hosp, Fac Med, Div Gastroenterol,Dept Pediat, Bangkok 10700, Thailand. [Broder-Fingert, Sarabeth] Boston Univ, Dept Pediat, Boston, MA 02215 USA. [Katz, Aubrey J.] Massachusetts Gen Hosp Children, Dept Pediat, Boston, MA USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Tanpowpong, P (reprint author), Mahidol Univ, Ramathibodi Hosp, Fac Med, Div Gastroenterol,Dept Pediat, Bangkok 10700, Thailand. EM tuinoi1@gmail.com NR 10 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1328-8067 EI 1442-200X J9 PEDIATR INT JI Pediatr. Int. PD OCT PY 2015 VL 57 IS 5 BP 1028 EP 1030 DI 10.1111/ped.12766 PG 3 WC Pediatrics SC Pediatrics GA CU8AQ UT WOS:000363763600049 PM 26508189 ER PT J AU Hasegawa, K Mansbach, JM Piedra, PA Dunn, MB Clark, S Sullivan, AF Camargo, CA AF Hasegawa, Kohei Mansbach, Jonathan M. Piedra, Pedro A. Dunn, Michelle B. Clark, Sunday Sullivan, Ashley F. Camargo, Carlos A., Jr. TI Eligibility for palivizumab prophylaxis in a cohort of children with severe bronchiolitis SO PEDIATRICS INTERNATIONAL LA English DT Article DE bronchiolitis; eligibility; guideline; palivizumab; prophylaxis ID SYNCYTIAL VIRUS-INFECTION; UPDATED GUIDANCE; YOUNG-CHILDREN; INCREASED RISK; UNITED-STATES; HOSPITALIZATION; INFANTS AB In 2014, the American Academy of Pediatrics (AAP) updated their recommendations for palivizumab prophylaxis for children who are at high risk for severe respiratory syncytial virus (RSV) infection. To investigate the potential impact of the more restrictive 2014 criteria on the eligibility for palivizumab prophylaxis, we applied the 2012 and 2014 AAP recommendations for palivizumab prophylaxis to a multicenter cohort of 2207 US children hospitalized for bronchiolitis. According to the 2012 AAP recommendations, 215 children (9.7%) were eligible for palivizumab prophylaxis, while 140 children (6.3%) would have been eligible based on the 2014 updated recommendations (34.9% relative decrease; 95%CI: 28.5-41.7%). The decrease was largely driven by the restriction of eligibility to preterm infants with gestational age <29weeks. Further development of and refinement of cost-effective approaches for the prevention of severe RSV infection are needed. C1 [Hasegawa, Kohei; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp, Boston, MA USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Dunn, Michelle B.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU National Institutes of Health (Bethesda, MD, USA) [U01 AI-67693, K23 AI-77801] FX We thank the MARC-30 investigators (Appendix I) for their ongoing dedication to bronchiolitis research. This study was supported by grants U01 AI-67693 and K23 AI-77801 from the National Institutes of Health (Bethesda, MD, USA). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. Dr Mansbach provided consultation to Regeneron Pharmaceuticals; Dr Piedra served on the RSV Advisory Board of Regeneron Pharmaceuticals and MedImmune. The other authors have no financial relationships relevant to this article to disclose. NR 10 TC 2 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1328-8067 EI 1442-200X J9 PEDIATR INT JI Pediatr. Int. PD OCT PY 2015 VL 57 IS 5 BP 1031 EP 1034 DI 10.1111/ped.12760 PG 4 WC Pediatrics SC Pediatrics GA CU8AQ UT WOS:000363763600050 PM 26508190 ER PT J AU Duran-Pinedo, AE Yost, S Frias-Lopez, J AF Duran-Pinedo, Ana E. Yost, Susan Frias-Lopez, Jorge TI Small RNA Transcriptome of the Oral Microbiome during Periodontitis Progression SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID VIRULENCE-GENE-EXPRESSION; SMALL NONCODING RNAS; ESCHERICHIA-COLI; SOLUBLE-RNAS; REGULATORY RNAS; IN-VIVO; MYCOBACTERIUM-TUBERCULOSIS; PORPHYROMONAS-GINGIVALIS; ETHANOLAMINE UTILIZATION; DIFFERENTIAL EXPRESSION AB The oral microbiome is one of the most complex microbial communities in the human body, and due to circumstances not completely understood, the healthy microbial community becomes dysbiotic, giving rise to periodontitis, a polymicrobial inflammatory disease. We previously reported the results of community-wide gene expression changes in the oral microbiome during periodontitis progression and identified signatures associated with increasing severity of the disease. Small noncoding RNAs (sRNAs) are key players in posttranscriptional regulation, especially in fast-changing environments such as the oral cavity. Here, we expanded our analysis to the study of the sRNA metatranscriptome during periodontitis progression on the same samples for which mRNA expression changes were analyzed. We observed differential expression of 12,097 sRNAs, identifying a total of 20 Rfam sRNA families as being overrepresented in progression and 23 at baseline. Gene ontology activities regulated by the differentially expressed (DE) sRNAs included amino acid metabolism, ethanolamine catabolism, signal recognition particle-dependent cotranslational protein targeting to membrane, intron splicing, carbohydrate metabolism, control of plasmid copy number, and response to stress. In integrating patterns of expression of protein coding transcripts and sRNAs, we found that functional activities of genes that correlated positively with profiles of expression of DE sRNAs were involved in pathogenesis, proteolysis, ferrous iron transport, and oligopeptide transport. These findings represent the first integrated sequencing analysis of the community-wide sRNA transcriptome of the oral microbiome during periodontitis progression and show that sRNAs are key regulatory elements of the dysbiotic process leading to disease. C1 [Duran-Pinedo, Ana E.; Yost, Susan; Frias-Lopez, Jorge] Forsyth Inst, Cambridge, MA 02142 USA. [Frias-Lopez, Jorge] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Frias-Lopez, J (reprint author), Forsyth Inst, Cambridge, MA 02142 USA. EM jfrias@forsyth.org FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [DE021553, DE021127] FX Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under awards DE021553 and DE021127. NR 74 TC 2 Z9 2 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2015 VL 81 IS 19 BP 6688 EP 6699 DI 10.1128/AEM.01782-15 PG 12 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA CU3XO UT WOS:000363459800017 PM 26187962 ER PT J AU Hecht, H Horichs, J Sheldon, S Quint, J Bowers, A AF Hecht, Heiko Hoerichs, Jenny Sheldon, Sarah Quint, Jessilin Bowers, Alex TI The effects of simulated vision impairments on the cone of gaze SO ATTENTION PERCEPTION & PSYCHOPHYSICS LA English DT Article DE Gaze perception; Eye contact; Head orientation; Gaze cone; Central vision loss; Cataracts ID VISUAL-ACUITY TEST; PERCEPTION; LOOKING; DIRECTION; ME AB Detecting the gaze direction of others is critical for many social interactions. We explored factors that may make the perception of mutual gaze more difficult, including the degradation of the stimulus and simulated vision impairment. To what extent do these factors affect the complex assessment of mutual gaze? Using an interactive virtual head whose eye direction could be manipulated by the subject, we conducted two experiments to assess the effects of simulated vision impairments on mutual gaze. Healthy subjects had to demarcate the center and the edges of the cone of gaze-that is, the range of gaze directions that are accepted for mutual gaze. When vision was impaired by adding a semitransparent white contrast reduction mask to the display (Exp. 1), judgments became more variable and more influenced by the head direction (indicative of a compensation strategy). When refractive blur was added (Exp. 1), the gaze cone shrank from 12.9A degrees (no blur) to 11.3A degrees (3-diopter lens), which cannot be explained by a low-level process but might reflect a tightening of the criterion for mutual gaze as a response to the increased uncertainty. However, the overall effects of the impairments were relatively modest. Elderly subjects (Exp. 2) produced more variability but did not differ qualitatively from the younger subjects. In the face of artificial vision impairments, compensation mechanisms and criterion changes allow us to perform better in mutual gaze perception than would be predicted by a simple extrapolation from the losses in basic visual acuity and contrast sensitivity. C1 [Hecht, Heiko; Hoerichs, Jenny] Johannes Gutenberg Univ Mainz, Dept Psychol, D-55099 Mainz, Germany. [Sheldon, Sarah; Bowers, Alex] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Sheldon, Sarah; Bowers, Alex] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Quint, Jessilin] Indiana Univ, Sch Optometry, Bloomington, IN USA. RP Hecht, H (reprint author), Johannes Gutenberg Univ Mainz, Dept Psychol, D-55099 Mainz, Germany. EM hecht@uni-mainz.de FU NIH [T35EY007149]; Alice J. Adler Fellowship from the Schepens Eye Research Institute FX Agnes Munch programmed the gaze cone task. This study was supported in part by NIH Grant No. T35EY007149 and by an Alice J. Adler Fellowship from the Schepens Eye Research Institute. NR 19 TC 1 Z9 1 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1943-3921 EI 1943-393X J9 ATTEN PERCEPT PSYCHO JI Atten. Percept. Psychophys. PD OCT PY 2015 VL 77 IS 7 BP 2399 EP 2408 DI 10.3758/s13414-015-0931-4 PG 10 WC Psychology; Psychology, Experimental SC Psychology GA CT7TP UT WOS:000363017700019 PM 26018645 ER PT J AU Liu, CY Stucker, I Chen, C Goodman, G McHugh, MK D'Amelio, AM Etzel, CJ Li, S Lin, XH Christiani, DC AF Liu, Chen-yu Stuecker, Isabelle Chen, Chu Goodman, Gary McHugh, Michelle K. D'Amelio, Anthony M., Jr. Etzel, Carol J. Li, Su Lin, Xihong Christiani, David C. TI Genome-wide Gene-Asbestos Exposure Interaction Association Study Identifies a Common Susceptibility Variant on 22q13.31 Associated with Lung Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LET-7 MICRORNA FAMILY; COPY NUMBER CHANGES; FUNCTIONAL ANNOTATION; BREAST-CANCER; EPIDEMIOLOGY; EXPRESSION; GENOTYPES; SMOKING; CELLS; DISEASES AB Background: Occupational asbestos exposure has been found to increase lung cancer risk in epidemiologic studies. Methods: We conducted an asbestos exposure-gene interaction analyses among several Caucasian populations who were current or ex-smokers. The discovery phase included 833 Caucasian cases and 739 Caucasian controls, and used a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNP) with gene-asbestos interaction effects. The top ranked SNPs from the discovery phase were replicated within the International Lung and Cancer Consortium (ILCCO). First, in silico replication was conducted in those groups that had GWAS and asbestos exposure data, including 1,548 cases and 1,527 controls. This step was followed by de novo genotyping to replicate the results from the in silico replication, and included 1,539 cases and 1,761 controls. Multiple logistic regression was used to assess the SNP-asbestos exposure interaction effects on lung cancer risk. Results: We observed significantly increased lung cancer risk among MIRLET7BHG (MIRLET7B host gene located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325 heterozygous and homozygous variant allele(s) carriers (P < 5 x 10(-7) by likelihood ratio test; df = 1). Among the heterozygous and homozygous variant allele(s) carriers of polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325, each unit increase in the natural log-transformed asbestos exposure score was associated with age-, sex-, smoking status, and center-adjusted ORs of 1.34 [95% confidence interval (CI), 1.18-1.51], 1.24 (95% CI, 1.14-1.35), 1.28 (95% CI, 1.17-1.40), and 1.26 (95% CI, 1.15-1.38), respectively, for lung cancer risk. Conclusion: Our findings suggest that MIRLET7BHG polymorphisms may be important predictive markers for asbestos exposure-related lung cancer. Impact: To our knowledge, our study is the first report using a systematic genome-wide analysis in combination with detailed asbestos exposure data and replication to evaluate asbestos-associated lung cancer risk. (C) 2015 AACR. C1 [Liu, Chen-yu; Li, Su; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Liu, Chen-yu] Natl Taiwan Univ, Inst Environm Hlth, Coll Publ Hlth, Taipei 10764, Taiwan. [Stuecker, Isabelle] INSERM, Unit U754, Villejuif, France. [Chen, Chu; Goodman, Gary] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Chen, Chu] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Chen, Chu] Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA USA. [McHugh, Michelle K.; D'Amelio, Anthony M., Jr.; Etzel, Carol J.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [D'Amelio, Anthony M., Jr.] Univ Texas Houston, Grad Sch Biomed Sci, Biomath Biostat Program, Houston, TX USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1401, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu OI LIU, CHEN-YU/0000-0002-4693-5667 FU NIH [CA092824, CA090578, CA074386, ES00002] FX This work was supported by the NIH (CA092824, CA090578, CA074386, and ES00002 to D.C. Christiani/Harvard studies). NR 74 TC 1 Z9 1 U1 3 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2015 VL 24 IS 10 BP 1564 EP 1573 DI 10.1158/1055-9965.EPI-15-0021 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CU3CR UT WOS:000363401800015 PM 26199339 ER PT J AU Kar, SP Tyrer, JP Li, QY Lawrenson, K Aben, KKH Anton-Culver, H Antonenkova, N Chenevix-Trench, G Baker, H Bandera, EV Bean, YT Beckmann, MW Berchuck, A Bisogna, M Bjorge, L Bogdanova, N Brinton, L Brooks-Wilson, A Butzow, R Campbell, I Carty, K Chang-Claude, J Chen, YA Chen, ZH Cook, LS Cramer, D Cunningham, JM Cybulski, C Dansonka-Mieszkowska, A Dennis, J Dicks, E Doherty, JA Dork, T du Bois, A Durst, M Eccles, D Easton, DF Edwards, RP Ekici, AB Fasching, PA Fridley, BL Gao, YT Gentry-Maharaj, A Giles, GG Glasspool, R Goode, EL Goodman, MT Grownwald, J Harrington, P Harter, P Hein, A Heitz, F Hildebrandt, MAT Hillemanns, P Hogdall, E Hogdall, CK Hosono, S Iversen, ES Jakubowska, A Paul, J Jensen, A Ji, BT Karlan, BY Kjaer, SK Kelemen, LE Kellar, M Kelley, J Kiemeney, LA Krakstad, C Kupryjanczyk, J Lambrechts, D Lambrechts, S Le, ND Lee, AW Lele, S Leminen, A Lester, J Levine, DA Liang, D Lissowska, J Lu, K Lubinski, J Lundvall, L Massuger, L Matsuo, K McGuire, V McLaughlin, JR McNeish, IA Menon, U Modugno, F Moysich, KB Narod, SA Nedergaard, L Ness, RB Nevanlinna, H Odunsi, K Olson, SH Orlow, I Orsulic, S Weber, RP Pearce, CL Pejovic, T Pelttari, LM Permuth-Wey, J Phelan, CM Pike, MC Poole, EM Ramus, SJ Risch, HA Rosen, B Rossing, MA Rothstein, JH Rudolph, A Runnebaum, IB Rzepecka, IK Salvesen, HB Schildkraut, JM Schwaab, I Shu, XO Shvetsov, YB Siddiqui, N Sieh, W Song, HL Southey, MC Sucheston-Campbell, LE Tangen, IL Teo, SH Terry, KL Thompson, PJ Timorek, A Tsai, YY Tworoger, SS van Altena, AM Van Nieuwenhuysen, E Vergote, I Vierkant, RA Wang-Gohrke, S Walsh, C Wentzensen, N Whittemore, AS Wicklund, KG Wilkens, LR Woo, YL Wu, XF Wu, AN Yang, HN Zheng, W Ziogas, A Sellers, TA Monteiro, ANA Freedman, ML Gayther, SA Pharoah, PDP AF Kar, Siddhartha P. Tyrer, Jonathan P. Li, Qiyuan Lawrenson, Kate Aben, Katja K. H. Anton-Culver, Hoda Antonenkova, Natalia Chenevix-Trench, Georgia Baker, Helen Bandera, Elisa V. Bean, Yukie T. Beckmann, Matthias W. Berchuck, Andrew Bisogna, Maria Bjorge, Line Bogdanova, Natalia Brinton, Louise Brooks-Wilson, Angela Butzow, Ralf Campbell, Ian Carty, Karen Chang-Claude, Jenny Chen, Yian Ann Chen, Zhihua Cook, Linda S. Cramer, Daniel Cunningham, Julie M. Cybulski, Cezary Dansonka-Mieszkowska, Agnieszka Dennis, Joe Dicks, Ed Doherty, Jennifer A. Doerk, Thilo du Bois, Andreas Duerst, Matthias Eccles, Diana Easton, Douglas F. Edwards, Robert P. Ekici, Arif B. Fasching, Peter A. Fridley, Brooke L. Gao, Yu-Tang Gentry-Maharaj, Aleksandra Giles, Graham G. Glasspool, Rosalind Goode, Ellen L. Goodman, Marc T. Grownwald, Jacek Harrington, Patricia Harter, Philipp Hein, Alexander Heitz, Florian Hildebrandt, Michelle A. T. Hillemanns, Peter Hogdall, Estrid Hogdall, Claus K. Hosono, Satoyo Iversen, Edwin S. Jakubowska, Anna Paul, James Jensen, Allan Ji, Bu-Tian Karlan, Beth Y. Kjaer, Susanne K. Kelemen, Linda E. Kellar, Melissa Kelley, Joseph Kiemeney, Lambertus A. Krakstad, Camilla Kupryjanczyk, Jolanta Lambrechts, Diether Lambrechts, Sandrina Le, Nhu D. Lee, Alice W. Lele, Shashi Leminen, Arto Lester, Jenny Levine, Douglas A. Liang, Dong Lissowska, Jolanta Lu, Karen Lubinski, Jan Lundvall, Lene Massuger, Leon Matsuo, Keitaro McGuire, Valerie McLaughlin, John R. McNeish, Iain A. Menon, Usha Modugno, Francesmary Moysich, Kirsten B. Narod, Steven A. Nedergaard, Lotte Ness, Roberta B. Nevanlinna, Heli Odunsi, Kunle Olson, Sara H. Orlow, Irene Orsulic, Sandra Weber, Rachel Palmieri Pearce, Celeste Leigh Pejovic, Tanja Pelttari, Liisa M. Permuth-Wey, Jennifer Phelan, Catherine M. Pike, Malcolm C. Poole, Elizabeth M. Ramus, Susan J. Risch, Harvey A. Rosen, Barry Rossing, Mary Anne Rothstein, Joseph H. Rudolph, Anja Runnebaum, Ingo B. Rzepecka, Iwona K. Salvesen, Helga B. Schildkraut, Joellen M. Schwaab, Ira Shu, Xiao-Ou Shvetsov, Yurii B. Siddiqui, Nadeem Sieh, Weiva Song, Honglin Southey, Melissa C. Sucheston-Campbell, Lara E. Tangen, Ingvild L. Teo, Soo-Hwang Terry, Kathryn L. Thompson, Pamela J. Timorek, Agnieszka Tsai, Ya-Yu Tworoger, Shelley S. van Altena, Anne M. Van Nieuwenhuysen, Els Vergote, Ignace Vierkant, Robert A. Wang-Gohrke, Shan Walsh, Christine Wentzensen, Nicolas Whittemore, Alice S. Wicklund, Kristine G. Wilkens, Lynne R. Woo, Yin-Ling Wu, Xifeng Wu, Anna Yang, Hannah Zheng, Wei Ziogas, Argyrios Sellers, Thomas A. Monteiro, Alvaro N. A. Freedman, Matthew L. Gayther, Simon A. Pharoah, Paul D. P. CA Australian Canc Study Australian Ovarian Canc Study Grp TI Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; TRANSCRIPTION FACTORS; SUSCEPTIBILITY LOCI; BREAST-CANCER; VARIANTS; MODELS; SET; POPULATION; CARCINOMA; PROFILES AB Background: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. Methods: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Results: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. Conclusion: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Impact: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. (C) 2015 AACR. C1 [Kar, Siddhartha P.; Dennis, Joe; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Tyrer, Jonathan P.; Baker, Helen; Dicks, Ed; Easton, Douglas F.; Harrington, Patricia; Song, Honglin; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England. [Li, Qiyuan; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Lawrenson, Kate; Lee, Alice W.; Pearce, Celeste Leigh; Pike, Malcolm C.; Ramus, Susan J.; Wu, Anna; Gayther, Simon A.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA. [Aben, Katja K. H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6525 ED Nijmegen, Netherlands. [Aben, Katja K. H.] Comprehens Canc Ctr Netherlands, Utrecht, Netherlands. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, Genet Epidemiol Res Inst, Irvine, CA 92717 USA. [Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandrov, Minsk, Byelarus. [Chenevix-Trench, Georgia; Australian Canc Study] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia. [Australian Ovarian Canc Study Grp] Peter MacCallum Canc Inst, East Melbourne, Vic, Australia. [Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Canc Prevent & Control, New Brunswick, NJ USA. [Bean, Yukie T.; Kellar, Melissa; Pejovic, Tanja] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Bean, Yukie T.; Kellar, Melissa; Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Beckmann, Matthias W.; Fasching, Peter A.; Hein, Alexander] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen EMN, D-91054 Erlangen, Germany. [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Bisogna, Maria; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA. [Bjorge, Line; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway. [Bjorge, Line; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, Bergen, Norway. [Bogdanova, Natalia; Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany. [Brinton, Louise; Ji, Bu-Tian; Wentzensen, Nicolas; Yang, Hannah] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Brooks-Wilson, Angela] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada. [Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Cent Hosp, HUS, Helsinki, Finland. [Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. [Campbell, Ian] Peter MacCallum Canc Ctr, Canc Genet Lab, Div Res, Melbourne, Vic, Australia. [Campbell, Ian; Southey, Melissa C.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Campbell, Ian] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia. [Carty, Karen; Glasspool, Rosalind; Paul, James] Beatson West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, Glasgow, Lanark, Scotland. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Chen, Yian Ann; Chen, Zhihua] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Biostat, Tampa, FL 33682 USA. [Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA. [Cramer, Daniel; Terry, Kathryn L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Ctr, Boston, MA 02115 USA. [Cramer, Daniel; Terry, Kathryn L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Rzepecka, Iwona K.] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol & Lab Diagnost, Warsaw, Poland. [Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Rzepecka, Iwona K.] Inst Oncol, Warsaw, Poland. [Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Sect Biostat & Epidemiol, Dept Community & Family Med, Lebanon, NH USA. [du Bois, Andreas; Harter, Philipp; Heitz, Florian] Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, Essen, Germany. [du Bois, Andreas; Harter, Philipp; Heitz, Florian] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany. [Duerst, Matthias; Runnebaum, Ingo B.] Univ Jena, Dept Gynecol, Jena Univ Hosp, Jena, Germany. [Eccles, Diana; Edwards, Robert P.] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Edwards, Robert P.; Modugno, Francesmary] Univ Pittsburgh, Ovarian Canc Ctr Excellence, Pittsburgh, PA USA. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Fridley, Brooke L.] Univ Kansas, Med Ctr, Biostat & Informat Shared Resource, Kansas City, KS 66103 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Elizabeth Garrett Anderson Inst Womens Hlth, Womens Canc, London, England. [Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Goode, Ellen L.; Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA. [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Dept Biomed Sci, Commun & Populat Hlth Res Inst, Los Angeles, CA 90048 USA. [Cybulski, Cezary; Grownwald, Jacek; Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Hillemanns, Peter] Hannover Med Sch, Dept Obstet, Hannover, Germany. [Hillemanns, Peter] Hannover Med Sch, Dept Gynaecol, Hannover, Germany. [Hogdall, Estrid; Jensen, Allan; Kjaer, Susanne K.] Danish Canc Soc, Res Ctr, Virus Lifestyle & Genes, Copenhagen, Denmark. [Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark. [Hogdall, Claus K.; Kjaer, Susanne K.; Lundvall, Lene] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark. [Hosono, Satoyo] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan. [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA. [Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Walsh, Christine] Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Kelemen, Linda E.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Kelley, Joseph] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium. [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium. [Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace] Univ Hosp Leuven, Dept Oncol, Div Gynecol Oncol, Leuven, Belgium. [Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada. [Lele, Shashi; Moysich, Kirsten B.; Sucheston-Campbell, Lara E.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA. [Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Massuger, Leon; van Altena, Anne M.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, NL-6525 ED Nijmegen, Netherlands. [Matsuo, Keitaro] Kyushu Univ, Dept Prevent Med, Fac Med Sci, Fukuoka 812, Japan. [McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Dept Hlth Res & Policy Epidemiol, Sch Med, Stanford, CA 94305 USA. [McLaughlin, John R.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [McNeish, Iain A.] Univ Glasgow, Inst Canc Sci, Wolfson Wohl Canc Res Ctr, Beatson Inst Canc Res, Glasgow, Lanark, Scotland. [Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA USA. [Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Narod, Steven A.] Womens Coll Res Inst, Toronto, ON, Canada. [Nedergaard, Lotte] Univ Copenhagen, Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Olson, Sara H.; Orlow, Irene; Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Weber, Rachel Palmieri] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Dansonka-Mieszkowska, Agnieszka; Permuth-Wey, Jennifer; Phelan, Catherine M.; Tsai, Ya-Yu; Sellers, Thomas A.; Monteiro, Alvaro N. A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [Rosen, Barry] Univ Toronto, Dept Gynecol Oncol, Princess Margaret Hosp, Toronto, ON, Canada. [Rosen, Barry] Univ Toronto, Fac Med, Dept Obstet & Gynecol, Toronto, ON, Canada. [Rossing, Mary Anne; Wicklund, Kristine G.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. [Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Schildkraut, Joellen M.] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC USA. [Schwaab, Ira] Inst Humangenet Wiesbaden, Wiesbaden, Germany. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Dept Med, Epidemiol Ctr, Div Epidemiol,Sch Med, Nashville, TN 37212 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Shvetsov, Yurii B.; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA. [Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow G4 0SF, Lanark, Scotland. [Teo, Soo-Hwang] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia. [Teo, Soo-Hwang; Woo, Yin-Ling] Univ Malaya, Fac Med, Univ Malaya Med Ctr, Univ Malaya Canc Res Inst, Kuala Lumpur, Malaysia. [Timorek, Agnieszka] Warsaw Med Univ, IInd Fac Med, Dept Obstet Gynecol & Oncol, Warsaw, Poland. [Timorek, Agnieszka] Brodnowski Hosp, Warsaw, Poland. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany. [Woo, Yin-Ling] Univ Malaya, Dept Obstet & Gynaecol, Univ Malaya Med Ctr, Kuala Lumpur, Malaysia. RP Kar, SP (reprint author), Univ Cambridge, Ctr Canc Genet Epidemiol, Strangeways Res Lab, Cambridge CB1 8RN, England. EM sk718@medschl.cam.ac.uk RI Hein, Alexander/F-6999-2010; Bandera, Elisa/M-4169-2014; Brooks-Wilson, Angela/E-9399-2012; van Altena, Anne/B-9824-2016; Teo, Soo-hwang/H-2353-2014; Aben, Katja/G-9686-2016; Bowtell, David/H-1007-2016; Dork, Thilo/J-8620-2012; Bjorge, Line/C-1307-2017; salvesen, Helga/C-1187-2017; OI Ramus, Susan/0000-0003-0005-7798; McNeish, Iain/0000-0002-9387-7586; Orlow, Irene/0000-0001-6234-6961; Krakstad, Camilla/0000-0002-0174-8139; Giles, Graham/0000-0003-4946-9099; Hein, Alexander/0000-0003-2601-3398; Kjaer, Susanne/0000-0002-8347-1398; Bandera, Elisa/0000-0002-8789-2755; Brooks-Wilson, Angela/0000-0003-1009-6408; Aben, Katja/0000-0002-0214-2147; Bowtell, David/0000-0001-9089-7525; Bjorge, Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831; Glasspool, Rosalind/0000-0002-5000-1680 FU European Commission [223175-HEALTH-F2-2009-223175]; U.S. National Cancer Institute GAME-ON Post-GWAS Initiative [U19-CA148112]; Ovarian Cancer Research Fund [PPD/RPCI.07]; Cancer Research UK Principal Research Fellowship; National Health and Medical Research Council of Australia; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; Canadian Institutes of Health Research Investigator award [MSH-87734]; U.S. National Institute of Environmental Health Sciences [T32ES013678]; U.S. National Cancer Institute [1K99CA184415-01]; Gates Cambridge Scholarship; NIH [R01-CA168758, R13-CA165638, P50-CA159981, R03-CA115195, R01-CA114343, R01-CA149429, T32-CA009001, R01-CA172404, R01-CA074850, P30-CA124435, K07-CA143047, R01-CA076016]; Cancer Research UK [C315/A2621, C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689]; American Cancer Society [CRTG-00-196-01-CCE]; California Cancer Research Program [00-01389V-20170, N01-CN25403, 2II0200]; Canadian Institutes for Health Research [MOP-86727]; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; Cancer Institute of New Jersey; Celma Mastry Ovarian Cancer Foundation; Danish Cancer Society [94-222-52]; ELAN Program of the University of Erlangen-Nuremberg; Eve Appeal; Helsinki University Central Hospital Research Fund; Helse Vest; Imperial Experimental Cancer Research Centre [C1312/A15589]; Norwegian Cancer Society; Norwegian Research Council; Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Ministry of Health Labour and Welfare of Japan; L&S Milken Foundation; Polish Ministry of Science and Higher Education [4 PO5C 028 14, 2 PO5A 068 27]; Malaysian Ministry of Higher Education [UM.C/HlR/MOHE/06]; Cancer Research Initiatives Foundation; Roswell Park Cancer Institute Alliance Foundation; U.S. National Institutes of Health [R03-CA115195, R01-CA114343, R01-CA149429, R01-CA074850, K07-CA143047, R01-CA076016, K07-CA095666, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA15083, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, UM1-CA186107, P01-CA87969, R01-CA49449, UM1-CA176726, R01-CA67262, R01-CA061107, R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA112523, R01-CA126841, R01-CA136924, R03-CA113148, R37-CA070867, R37-CA70867, U01-CA069417, U01-CA071966]; U.S. Army Medical Research and Material Command [DAMD17-98-1-8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-10-1-0280]; National Health and Medical Research Council of Australia [199600, 400281]; German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research [01 GB 9401]; state of Baden-Wurttemberg through Medical Faculty of the University of Ulm [P. 685]; Minnesota Ovarian Cancer Alliance; Mayo Foundation; Fred C. and Katherine B. Andersen Foundation; Lon V. Smith Foundation [LVS-39420]; Oak Foundation; OHSU Foundation; Mermaid I project; Rudolf-Bartling Foundation; Royal Marsden Hospital; WorkSafeBC; U.K. National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital "Womens Health Theme" FX Funding for the COGS infrastructure came from a European Commission's Seventh Framework Programme grant (agreement number 223175-HEALTH-F2-2009-223175). The scientific development and funding for this project were, in part, supported by the U.S. National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). Funding for the Ovarian Cancer Association Consortium (OCAC) GWAS infrastructure came from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). D.F. Easton is supported by a Cancer Research UK Principal Research Fellowship. G. Chenevix-Trench is supported by the National Health and Medical Research Council of Australia. B.Y. Karlan is supported by an American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). L.E. Keleman was supported by a Canadian Institutes of Health Research Investigator award (MSH-87734). A.W. Lee is supported by a T32 grant from the U.S. National Institute of Environmental Health Sciences (T32ES013678). K. Lawrenson is supported by a K99/R00 grant from the U.S. National Cancer Institute (1K99CA184415-01). S.P. Kar is supported by a Gates Cambridge Scholarship.; The following authors would like to acknowledge specific grant support from the NIH: J.A. Doherty (R01-CA168758), R.P. Edwards (R13-CA165638), K. Odunsi (P50-CA159981), C.L. Pearce (R03-CA115195), J. Permuth-Wey (R01-CA114343), C.M. Phelan (R01-CA149429), E.M. Poole (T32-CA009001), S.J. Ramus (R01-CA172404), H.A. Risch (R01-CA074850), J.H. Rothstein (P30-CA124435), W. Sieh (K07-CA143047), L.E. Sucheston-Campbell (P50-CA159981), Rachel Palmieri Weber (R01-CA076016); and from Cancer Research UK: A. Gentry-Maharaj (C315/A2621) and P.D.P. Pharoah (C490/A10119). Funding of the constituent studies of the OCAC GWAS and COGS are listed by funding agency with each grant number in parentheses: American Cancer Society (CRTG-00-196-01-CCE); the California Cancer Research Program (00-01389V-20170, N01-CN25403, 2II0200); the Canadian Institutes for Health Research (MOP-86727); Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086, and C536/A6689); the Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; Imperial Experimental Cancer Research Centre (C1312/A15589); the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health Labour and Welfare of Japan; the L&S Milken Foundation; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; the Roswell Park Cancer Institute Alliance Foundation; the U.S. National Institutes of Health (K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA15083, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, UM1-CA186107, P01-CA87969, R01-CA49449, UM1-CA176726, R01-CA67262, R01-CA061107, R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R37-CA70867, U01-CA069417, U01-CA071966, and Intramural research funds); the U.S. Army Medical Research and Material Command (DAMD17-98-1-8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, and W81XWH-10-1-0280); the National Health and Medical Research Council of Australia (199600 and 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401); the state of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P. 685); the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the U.K.; National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital "Womens Health Theme" and the Royal Marsden Hospital; WorkSafeBC. NR 52 TC 4 Z9 4 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2015 VL 24 IS 10 BP 1574 EP 1584 DI 10.1158/1055-9965.EPI-14-1270 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CU3CR UT WOS:000363401800016 PM 26209509 ER PT J AU Schneider, BG Mera, R Piazuelo, MB Bravo, JC Zabaleta, J Delgado, AG Bravo, LE Wilson, KT El-Rifai, W Peek, RM Correa, P AF Schneider, Barbara G. Mera, Robertino Piazuelo, M. Blanca Bravo, Juan C. Zabaleta, Jovanny Delgado, Alberto G. Bravo, Luis E. Wilson, Keith T. El-Rifai, Wael Peek, Richard M., Jr. Correa, Pelayo TI DNA Methylation Predicts Progression of Human Gastric Lesions SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HELICOBACTER-PYLORI INFECTION; E-CADHERIN GENE; CANCER-RISK; HYPERMETHYLATION; AGE; CLASSIFICATION; CELLS; ERADICATION; BIOPSIES; COHORT AB Background: Development of the intestinal subtype of gastric adenocarcinoma is marked by a progression of histopathologic lesions. Residents of the Andean regions of Colombia are at high risk for gastric cancer. Methods: A cohort of 976 Colombian subjects was followed over 16 years examining effects of Helicobacter pylori eradication and treatment with antioxidants on progression of lesions. We performed methylation analysis of DNA from baseline antral biopsies from 104 subjects for whom follow-up data were available for at least 12 years. Methylation was quantitated for AMPH, CDKN2A, CDH1, EN1, EMX1, NKX6-1, PCDH10, RPRM, RSPO2, SORCS3, ZIC1, and ZNF610 genes, using Pyrosequencing. Results: Levels of DNA methylation were associated with baseline diagnosis for AMPH, EMX1, RPRM, RSPO2, SORCS3, and ZNF610. After adjusting for baseline diagnosis and H. pylori infection, methylation levels of AMPH, PCDH10, RSPO2, and ZNF610 had progression coefficients that increased and P values that decreased over 6, 12, and 16 years. Methylation for SORCS3 was associated with progression at all 3 time points but without the continual strengthening of the effect. Scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes were unrelated to progression. Conclusions: Methylation levels of AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 predict progression of gastric lesions independent of the effect of duration of H. pylori infection, baseline diagnosis, gender of the patient, or scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes. Impact: DNA methylation levels in AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 may contribute to identification of persons with gastric lesions likely to progress. (C) 2015 AACR. C1 [Schneider, Barbara G.; Mera, Robertino; Piazuelo, M. Blanca; Delgado, Alberto G.; Wilson, Keith T.; Peek, Richard M., Jr.; Correa, Pelayo] Vanderbilt Univ, Med Ctr, Dept Med, Div Gastroenterol, Nashville, TN 37232 USA. [Bravo, Juan C.] Fdn Valle Lili, Cali, Colombia. [Zabaleta, Jovanny] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA USA. [Zabaleta, Jovanny] Stanley Scott Canc Ctr, New Orleans, LA USA. [Bravo, Luis E.] Univ Valle, Sch Med, Dept Pathol, Cali, Colombia. [Wilson, Keith T.; El-Rifai, Wael] Vet Affairs Tennessee Valley Healthcare Syst, Nashville, TN USA. [Wilson, Keith T.; El-Rifai, Wael] US Dept Vet Affairs, Off Med Res, Nashville, TN USA. [El-Rifai, Wael] Vanderbilt Univ, Med Ctr, Dept Surg, Nashville, TN 37232 USA. RP Schneider, BG (reprint author), Vanderbilt Univ, Med Ctr, 2215 Garland Ave,Room 1030C MRB 4, Nashville, TN 37232 USA. EM barbara.schneider@vanderbilt.edu OI Schneider, Barbara/0000-0003-4421-1355 FU National Center for Research Resources [UL1 RR024975-01]; National Center for Advancing Translational Sciences [2 UL2 TR000445-06]; Department of Veterans Affairs [I01 BX001453]; [P01 CA28842]; [R01 CA77955]; [R01 CA177372]; [P01 CA116087]; [P30 DK058404]; [R01 DK053620]; [R01 CA190612]; [R01 DK58587] FX This study was supported by the National Center for Research Resources, grant UL1 RR024975-01, which is now at the National Center for Advancing Translational Sciences, Grant 2 UL2 TR000445-06 (by a pilot grant to B.G. Schneider); grants P01 CA28842 (to P. Correa, K.T. Wilson, and L.E. Bravo), R01 CA77955 (to R.M. Peek Jr.), R01 CA177372 (to W. El-Rifai), P01 CA116087 (to R.M. Peek Jr.), P30 DK058404 (to R.M. Peek Jr.), R01 DK053620 (to K.T. Wilson), R01 CA190612 (to K.T. Wilson), R01 DK58587 (to R.M. Peek Jr.); and grant I01 BX001453 (to K.T. Wilson) from the Department of Veterans Affairs. NR 50 TC 4 Z9 5 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2015 VL 24 IS 10 BP 1607 EP 1613 DI 10.1158/1055-9965.EPI-15-0388 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CU3CR UT WOS:000363401800020 PM 26269563 ER PT J AU Abel, GA Cronin, AM Earles, K Gray, SW AF Abel, Gregory A. Cronin, Angel M. Earles, Kristofer Gray, Stacy W. TI Accessibility and Quality of Online Cancer-Related Clinical Trial Information for Naive Searchers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INTERNET; PARTICIPATION; DISPARITIES; ATTITUDES; AWARENESS AB Although the Internet may help to increase cancer patients' awareness of clinical trials, little is known about the accessibility and quality of online clinical trial information. We simulated the experience of a naive cancer patient without clinical trial knowledge by searching three popular search engines for treatment information for breast, lung, and prostate cancer, and myelodysplastic syndromes (MDS). Two coders independently evaluated website content for accessibility and quality. We screened 120 websites and identified 40 unique sites for analysis. Overall, 85% [95% confidence interval (CI), 70%-94%] of sites mentioned clinical trials on the landing page and 68% (51%-81%) included links to specific trials. Overall readability was poor. Approximately half of websites (36%-68%) included information on the potential benefits and risks of clinical trials and 40% provided information about when the site had been updated (25%-57%). Among sites with links to specific clinical trials, only 44% (25%-65%) provided an interactive interface that would allow patients to customize search results; breast (100%) and prostate (50%) sites were more interactive than lung (25%) and MDS (14%; P = 0.007). Although cancer clinical trial information is widely available on the Internet, its quality is highly variable. Given the fact that many emerging cancer therapeutics are personalized based on disease or genomic characteristics, interactive web-based interfaces could serve as powerful vehicles to help patients locate appropriate clinical trials. Without enhanced efforts to ensure greater interactivity of cancer treatment websites, patient awareness of relevant clinical trials may remain low. (C) 2015 AACR. C1 [Abel, Gregory A.; Cronin, Angel M.; Gray, Stacy W.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02215 USA. [Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Oncol, Boston, MA 02215 USA. [Abel, Gregory A.; Gray, Stacy W.] Harvard Univ, Sch Med, Boston, MA USA. [Earles, Kristofer] Univ Massachusetts, Sch Med, Worcester, MA USA. [Gray, Stacy W.] Dana Farber Canc Inst, Dept Med Oncol, Div Thorac Oncol, Boston, MA 02215 USA. RP Abel, GA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1108, Boston, MA 02215 USA. EM gregory_abel@dfci.harvard.edu FU American Cancer Society [120529-MRSG-11-006-01-CPPB]; National Human Genome Research Institute [U01HG006492] FX S.W. Gray is supported by the American Cancer Society (120529-MRSG-11-006-01-CPPB) and the National Human Genome Research Institute (U01HG006492). NR 17 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2015 VL 24 IS 10 BP 1629 EP 1631 DI 10.1158/1055-9965.EPI-15-0274 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CU3CR UT WOS:000363401800023 PM 26265204 ER PT J AU Krishnadas, DK Shusterman, S Bai, FQ Diller, L Sullivan, JE Cheerva, AC George, RE Lucas, KG AF Krishnadas, Deepa K. Shusterman, Suzanne Bai, Fanqi Diller, Lisa Sullivan, Janice E. Cheerva, Alexandra C. George, Rani E. Lucas, Kenneth G. TI A phase I trial combining decitabine/dendritic cell vaccine targeting MAGE-A1, MAGE-A3 and NY-ESO-1 for children with relapsed or therapy-refractory neuroblastoma and sarcoma SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Cancer germline genes; Decitabine; Dendritic cell vaccine; Immunotherapy; Neuroblastoma; Sarcoma ID COLONY-STIMULATING FACTOR; OVARIAN-CANCER; T-CELLS; GENE-EXPRESSION; DENDRITIC CELLS; TUMOR-ANTIGEN; SOLID TUMORS; 5-AZA-2'-DEOXYCYTIDINE; IMMUNOTHERAPY; COMBINATION AB Antigen-specific immunotherapy was studied in a multi-institutional phase 1/2 study by combining decitabine (DAC) followed by an autologous dendritic cell (DC)/MAGE-A1, MAGE-A3 and NY-ESO-1 peptide vaccine in children with relapsed/refractory solid tumors. Patients aged 2.5-15 years with relapsed neuroblastoma, Ewing's sarcoma, osteosarcoma and rhabdomyosarcoma were eligible to receive DAC followed by DC pulsed with overlapping peptides derived from full-length MAGE-A1, MAGE-A3 and NY-ESO-1. The primary endpoints were to assess the feasibility and tolerability of this regimen. Each of four cycles consisted of week 1: DAC 10 mg/m(2)/day for 5 days and weeks 2 and 3: DC vaccine once weekly. Fifteen patients were enrolled in the study, of which 10 were evaluable. Generation of DC was highly feasible for all enrolled patients. The treatment regimen was generally well tolerated, with the major toxicity being DAC-related myelosuppression in 5/10 patients. Six of nine patients developed a response to MAGE-A1, MAGE-A3 or NY-ESO-1 peptides post-vaccine. Due to limitations in number of cells available for analysis, controls infected with a virus encoding relevant genes have not been performed. Objective responses were documented in 1/10 patients who had a complete response. Of the two patients who had no evidence of disease at the time of treatment, one remains disease-free 2 years post-therapy, while the other experienced a relapse 10 months post-therapy. The chemoimmunotherapy approach using DAC/DC-CT vaccine is feasible, well tolerated and results in antitumor activity in some patients. Future trials to maximize the likelihood of T cell responses post-vaccine are warranted. C1 [Krishnadas, Deepa K.; Bai, Fanqi; Sullivan, Janice E.; Cheerva, Alexandra C.; Lucas, Kenneth G.] Univ Louisville, Dept Pediat, Hematol Oncol, Louisville, KY 40202 USA. [Shusterman, Suzanne; Diller, Lisa; George, Rani E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02215 USA. [Shusterman, Suzanne; Diller, Lisa; George, Rani E.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA 02215 USA. RP George, RE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Dana 640E,450 Brookline Ave, Boston, MA 02215 USA. EM Rani_George@dfci.harvard.edu; k0luca01@louisville.edu FU Hyundai Hope on Wheels; Solving Kids' Cancer; Andrew McDonough B + Foundation; Pierce Phillips Charity; Dana-Farber Cancer Institute (DFCI) Neuroblastoma Fund FX We thank the clinical research staff at the Dana-Farber Cancer Institute (DFCI), Kosair Charities Pediatric Clinical Research Unit and Penn State Children's Hospital. The work was supported by funds from Hyundai Hope on Wheels, Solving Kids' Cancer, The Andrew McDonough B + Foundation, the Pierce Phillips Charity and the Dana-Farber Cancer Institute (DFCI) Neuroblastoma Fund. We thank all the patients enrolled in this trial and their families for their participation in the study. NR 34 TC 10 Z9 12 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD OCT PY 2015 VL 64 IS 10 BP 1251 EP 1260 DI 10.1007/s00262-015-1731-3 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CU0YZ UT WOS:000363246900004 PM 26105625 ER PT J AU Derks, S Nason, KS Liao, XY Stachler, MD Liu, KX Bin Liu, J Sicinska, E Goldberg, MS Freeman, GJ Rodig, SJ Davison, JM Bass, AJ AF Derks, Sarah Nason, Katie S. Liao, Xiaoyun Stachler, Matthew D. Liu, Kevin X. Bin Liu, Jie Sicinska, Ewa Goldberg, Michael S. Freeman, Gordon J. Rodig, Scott J. Davison, Jon M. Bass, Adam J. TI Epithelial PD-L2 Expression Marks Barrett's Esophagus and Esophageal Adenocarcinoma SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID T-CELL-ACTIVATION; CANCER; ENGAGEMENT; TOLERANCE; CARCINOMA; RESPONSES; LIGAND; B7-H1; B7-DC AB Esophageal adenocarcinoma is an increasingly common disease with a dismal 5-year survival rate of 10% to 15%. In the first systematic evaluation of the PD-1 pathway in esophageal adenocarcinoma, we identify expression of PD-L2 in cancer cells in 51.7% of esophageal adenocarcinomas. Epithelial PD-L1 was expressed on only 2% of cases, although PD-L1(+) immune cells were observed in 18% of esophageal adenocarcinomas. We also evaluated expression in the precursor lesion of esophageal adenocarcinoma, Barrett's esophagus, which emerges following gastric reflux-induced esophageal inflammation, and found PD-L2 expression in Barrett's esophagus but not in non-Barrett's esophagus esophagitis. Because the progression from squamous esophagitis to Barrett's esophagus is accompanied by a transition from a TH1 to TH2 immune response, we hypothesized that the TH2 cytokines IL4/IL13 could contribute to PD-L2 induction. We confirmed that these cytokines can augment PD-L2 expression in esophageal adenocarcinoma cell lines. These results suggest that the inflammatory environment in Barrett's esophagus and esophageal adenocarcinoma may contribute to the expression of PD-L2. Furthermore, the potential for PD-1 receptor blockade to be effective in esophageal adenocarcinomas with epithelial PD-L2 or immune cell PD-L1 expression should be evaluated in clinical trials. (C) 2015 AACR. C1 [Derks, Sarah; Liao, Xiaoyun; Stachler, Matthew D.; Liu, Kevin X.; Bin Liu, Jie; Sicinska, Ewa; Freeman, Gordon J.; Bass, Adam J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Derks, Sarah] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, Netherlands. [Nason, Katie S.] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Liao, Xiaoyun] Dana Farber Canc Inst, Dept Ctr Immunooncol, Boston, MA 02115 USA. [Stachler, Matthew D.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sicinska, Ewa] Dana Farber Canc Inst, Dept Mol Oncol Pathol, Boston, MA 02115 USA. [Goldberg, Michael S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Davison, Jon M.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Bass, Adam J.] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA. RP Bass, AJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM davisonjm@upmc.edu; adam_bass@dfci.harvard.edu FU Dutch Cancer Society [VU 2012-535]; National Cancer Institute [K07CA511613, P01 CA098101]; Center of Immune Oncology at Dana-Farber Cancer Institute [R01AI089955]; Target Cancer Foundation FX The project described was supported by the Dutch Cancer Society (VU 2012-535 to S. Derks), the National Cancer Institute K07CA511613 (K.S. Nason), P01 CA098101 (A.J. Bass), the Center of Immune Oncology at Dana-Farber Cancer Institute (X. Liao and S.J. Rodig), R01AI089955 (G.J. Freeman), and Target Cancer Foundation (A.J. Bass and M.S. Goldberg). NR 24 TC 12 Z9 12 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD OCT PY 2015 VL 3 IS 10 BP 1123 EP 1129 DI 10.1158/2326-6066.CIR-15-0046 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA CU3FA UT WOS:000363408400003 PM 26081225 ER PT J AU Callea, M Albiges, L Gupta, M Cheng, SC Genega, EM Fay, AP Song, JX Carvo, I Bhatt, RS Atkins, MB Hodi, FS Choueiri, TK McDermott, DF Freeman, GJ Signoretti, S AF Callea, Marcella Albiges, Laurence Gupta, Mamta Cheng, Su-Chun Genega, Elizabeth M. Fay, Andre P. Song, Jiaxi Carvo, Ingrid Bhatt, Rupal S. Atkins, Michael B. Hodi, F. Stephen Choueiri, Toni K. McDermott, David F. Freeman, Gordon J. Signoretti, Sabina TI Differential Expression of PD-L1 between Primary and Metastatic Sites in Clear-Cell Renal Cell Carcinoma SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID DOSE INTERLEUKIN-2; KIDNEY CANCER; B7-H1; THERAPY; OUTCOMES; TARGET; TRIAL AB PD-L1 expression in primary clear-cell renal cell carcinoma (ccRCC) increases the likelihood of response to anti-PD-1 inhibition, but fails to identify all responders. We hypothesized that PD-L1 levels assessed in randomly selected areas of the primary tumors may not accurately reflect expression levels in metastatic lesions, which are the target of systemic therapy. Therefore, we compared PD-L1 expression in a series of primary ccRCC and their metastases. Tissue blocks from 53 primary ccRCCs and 76 corresponding metastases were retrieved. Areas with predominant and highest nuclear grade were selected. Slides were immunostained with a validated anti-PD-L1 antibody (405.9A11). Membranous expression in tumor cells was quantified using H-score. Expression in tumor-infiltrating mononuclear cells (TIMC) was quantified using a combined score. Discordant tumor cell PD-L1 staining between primary tumors and metastases was observed in 11 of 53 cases (20.8%). Overall, tumor cell PD-L1 levels were not different in primary tumors and metastases (P = 0.51). Tumor cell PD-L1 positivity was associated with higher T stage (P = 0.03) and higher Fuhrman nuclear grade (P < 0.01). Within individual lesions, PD-L1 positivity was heterogeneous and almost exclusively detected in high nuclear grade areas (P < 0.001). No difference was found in PD-L1 levels in TIMCs between primary tumors and metastases (P = 0.82). The heterogeneity of PD-L1 expression in ccRCC suggests that its assessment as a predictive biomarker for PD-1 blockade may require analysis of metastatic lesions. Notably, because PD-L1 expression was mostly detected in high nuclear grade areas, to avoid false-negative results, these areas should be specifically selected for assessment. (C) 2015 AACR. C1 [Callea, Marcella; Song, Jiaxi; Carvo, Ingrid; Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Albiges, Laurence; Fay, Andre P.; Hodi, F. Stephen; Choueiri, Toni K.; Freeman, Gordon J.; Signoretti, Sabina] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gupta, Mamta] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Gupta, Mamta; Cheng, Su-Chun; Bhatt, Rupal S.; Choueiri, Toni K.; McDermott, David F.; Signoretti, Sabina] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA USA. [Cheng, Su-Chun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Genega, Elizabeth M.] Tufts Med Ctr, Dept Pathol, Boston, MA USA. [Bhatt, Rupal S.; McDermott, David F.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Signoretti, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Thorn Bldg 504A, Boston, MA 02115 USA. EM ssignoretti@partners.org FU DF/HCC Kidney Cancer SPORE [P50 CA101942-01]; Trust Family; Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute FX This work was supported by the DF/HCC Kidney Cancer SPORE P50 CA101942-01 to S. Signoretti, D.F. McDermott, G.J. Freeman, and T.K. Choueiri. This study was also funded in part by the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute for T.K. Choueiri. NR 30 TC 33 Z9 33 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD OCT PY 2015 VL 3 IS 10 BP 1158 EP 1164 DI 10.1158/2326-6066.CIR-15-0043 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA CU3FA UT WOS:000363408400007 PM 26014095 ER PT J AU Tirumani, SH Ramaiya, NH Keraliya, A Bailey, ND Ott, PA Hodi, FS Nishino, M AF Tirumani, Sree Harsha Ramaiya, Nikhil H. Keraliya, Abhishek Bailey, Nancy D. Ott, Patrick A. Hodi, F. Stephen Nishino, Mizuki TI Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID HIGH-RESOLUTION CT; TERM-FOLLOW-UP; METASTATIC MELANOMA; RESPONSE CRITERIA; CTLA-4 BLOCKADE; ANTI-CTLA-4 ANTIBODY; INDUCED HYPOPHYSITIS; MONOCLONAL-ANTIBODY; PLUS IPILIMUMAB; B7 FAMILY AB Ipilimumab is a promising novel immunotherapy agent and is associated with a variety of immune-related adverse events (irAE). The purpose of this study was to investigate the manifestations of irAEs on body imaging in patients with advanced melanoma treated with ipilimumab. One-hundred forty-seven patients with advanced melanoma (59 women, 88 men; median age, 64.5 years) treated with ipilimumab were studied. All patients had the baseline and at least one follow-up chest/abdomen/pelvis CT or PET/CT during therapy, which were reviewed by a consensus of two radiologists blinded to the clinical data. Findings indicative of individual types of irAEs were assessed, including thyroiditis, sarcoid-like lymphadenopathy, pneumonitis, hepatitis, pancreatitis, and colitis. Among the 147 patients, 46 (31%) had radiologically identified irAEs. The time interval from the initiation of therapy to the development of irAEs was less than 3 months in 76% (35 of 46) of the patients (range, 0.2-9.1months). Clinical characteristics did not differ between patients with and without irAEs (P > 0.18). Among the individual types of irAEs, colitis was most common (n = 28; 19%), followed by sarcoid-like lymphadenopathy (n = 8; 5%) and pneumonitis (n = 8; 5%). Hepatitis (n = 3), thyroiditis (n = 2), and pancreatitis (n = 1) were less common. The resolution of irAEs was noted in 32 of 36 patients (89%) with further follow-up scans, with a median time of 2.3 months after the detection of irAE. In conclusion, irAEs were noted on body imaging in 31% of patients with melanoma treated with ipilimumab. Colitis was the most common, followed by sarcoid-like lymphadenopathy and pneumonitis. The results call for an increased awareness of irAEs, given the expanding role of cancer immunotherapy. (C) 2015 AACR. C1 [Tirumani, Sree Harsha; Ramaiya, Nikhil H.; Keraliya, Abhishek; Nishino, Mizuki] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Ramaiya, Nikhil H.; Keraliya, Abhishek; Nishino, Mizuki] Dana Farber Canc Inst, Boston, MA 02215 USA. [Bailey, Nancy D.; Ott, Patrick A.; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bailey, Nancy D.; Ott, Patrick A.; Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Ctr, Boston, MA 02215 USA. [Bailey, Nancy D.; Ott, Patrick A.; Hodi, F. Stephen] Brigham & Womens Hosp, Boston, MA 02215 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@dfci.harvard.edu FU Bristol-Myers Squibb FX F.S. Hodi reports receiving commercial research support from Bristol-Myers Squibb, has ownership interest in a pending patent on MICA antibodies, and is a nonpaid consultant for Bristol-Myers Squibb. M. Nishino is a consultant/advisory board member for Bristol-Myers Squibb. No potential conflicts of interest were disclosed by the other authors. NR 48 TC 9 Z9 9 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD OCT PY 2015 VL 3 IS 10 BP 1185 EP 1192 DI 10.1158/2326-6066.CIR-15-0102 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA CU3FA UT WOS:000363408400010 PM 26100356 ER PT J AU Hadac, JN Leystra, AA Olson, TJP Maher, ME Payne, SN Yueh, AE Schwartz, AR Albrecht, DM Clipson, L Pasch, CA Matkowskyj, KA Halberg, RB Deming, DA AF Hadac, Jamie N. Leystra, Alyssa A. Olson, Terrah J. Paul Maher, Molly E. Payne, Susan N. Yueh, Alexander E. Schwartz, Alexander R. Albrecht, Dawn M. Clipson, Linda Pasch, Cheri A. Matkowskyj, Kristina A. Halberg, Richard B. Deming, Dustin A. TI Colon Tumors with the Simultaneous Induction of Driver Mutations in APC, KRAS, and PIK3CA Still Progress through the Adenoma-to-carcinoma Sequence SO CANCER PREVENTION RESEARCH LA English DT Article ID MULTIPLE INTESTINAL NEOPLASIA; ONCOGENIC K-RAS; COLORECTAL-CANCER; GENE-THERAPY; MOUSE; MICE; MODEL; TUMORIGENESIS; POLYPOSIS; DELIVERY AB Human colorectal cancers often possess multiple mutations, including three to six driver mutations per tumor. The timing of when these mutations occur during tumor development and progression continues to be debated. More advanced lesions carry a greater number of driver mutations, indicating that colon tumors might progress from adenomas to carcinomas through the stepwise accumulation of mutations following tumor initiation. However, mutations that have been implicated in tumor progression have been identified in normal-appearing epithelial cells of the colon, leaving the possibility that these mutations might be present before the initiation of tumorigenesis. We utilized mouse models of colon cancer to investigate whether tumorigenesis still occurs through the adenoma-to-carcinoma sequence when multiple mutations are present at the time of tumor initiation. To create a model in which tumors could concomitantly possess mutations in Apc, Kras, and Pik3ca, we developed a novel minimally invasive technique to administer an adenovirus expressing Cre recombinase to a focal region of the colon. Here, we demonstrate that the presence of these additional driver mutations at the time of tumor initiation results in increased tumor multiplicity and an increased rate of progression to invasive adenocarcinomas. These cancers can even metastasize to retroperitoneal lymph nodes or the liver. However, despite having as many as three concomitant driver mutations at the time of initiation, these tumors still proceed through the adenoma-to-carcinoma sequence. (C) 2015 AACR. C1 [Hadac, Jamie N.; Leystra, Alyssa A.; Clipson, Linda] Univ Wisconsin, Dept Oncol, Madison, WI 53792 USA. [Olson, Terrah J. Paul] Univ Wisconsin, Dept Surg, Div Gen Surg, Madison, WI 53792 USA. [Maher, Molly E.; Yueh, Alexander E.; Deming, Dustin A.] Univ Wisconsin, Div Hematol & Oncol, Madison, WI 53792 USA. [Payne, Susan N.; Pasch, Cheri A.; Matkowskyj, Kristina A.; Halberg, Richard B.; Deming, Dustin A.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53792 USA. [Schwartz, Alexander R.; Albrecht, Dawn M.; Halberg, Richard B.] Univ Wisconsin, Dept Med, Div Gastroenterol & Hepatol, Madison, WI 53792 USA. [Matkowskyj, Kristina A.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53792 USA. [Matkowskyj, Kristina A.; Deming, Dustin A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Deming, DA (reprint author), Univ Wisconsin, 600 Highland Ave,K6-544, Madison, WI 53792 USA. EM ddeming@medicine.wisc.edu FU Funk Out Cancer; Conquer Cancer Foundation of the American Society of Clinical Oncology; NIH [T32 CA09017, T32 CA009135, R21 CA170876, R01 CA123438]; AACR Career Development Award for Colorectal Cancer Research [12-20-01-HALB]; UW Division of Gastroenterology and Hepatology; UW Department of Medicine; UW School of Medicine and Public Health; UW Carbone Cancer Center; UW Graduate School through the Wisconsin Alumni Research Foundation; University of Wisconsin Carbone Cancer Center [P30 CA014520]; UW Carbone Cancer Center Gastrointestinal Disease Oriented Working Group FX This work was partially funded by Funk Out Cancer, a memorial event dedicated to Kate Gates Falaschi. This work was also supported by the Conquer Cancer Foundation of the American Society of Clinical Oncology through A Young Investigator Award (to D.A. Deming); T32 CA09017 (to T.J. Paul Olson), T32 CA009135 (to J.N. Hadac. and A. A. Leystra), R21 CA170876 (to R.B. Halberg) and R01 CA123438 (to R.B. Halberg) from the NIH; 2012 AACR Career Development Award for Colorectal Cancer Research, Grant Number 12-20-01-HALB (to R.B. Halberg); start-up funds (to R.B. Halberg) from the UW Division of Gastroenterology and Hepatology, the UW Department of Medicine, and the UW School of Medicine and Public Health; and start-up funds (to D.A. Deming) from the UW Carbone Cancer Center, UW Department of Medicine, UW School of Medicine and Public Health, and the UW Graduate School through the Wisconsin Alumni Research Foundation; P30 CA014520 (Core Grant, University of Wisconsin Carbone Cancer Center); UW Carbone Cancer Center Gastrointestinal Disease Oriented Working Group (to R.B. Halberg and D.A. Deming); and Funk Out Cancer (to D.A. Deming). NR 50 TC 4 Z9 4 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2015 VL 8 IS 10 BP 952 EP 961 DI 10.1158/1940-6207.CAPR-15-0003 PG 10 WC Oncology SC Oncology GA CU3BS UT WOS:000363399200009 PM 26276752 ER PT J AU Karakasheva, TA Waldron, TJ Eruslanov, E Kim, SB Lee, JS O'Brien, S Hicks, PD Basu, D Singhal, S Malavasi, F Rustgi, AK AF Karakasheva, Tatiana A. Waldron, Todd J. Eruslanov, Evgeniy Kim, Sang-Bae Lee, Ju-Seog O'Brien, Shaun Hicks, Philip D. Basu, Devraj Singhal, Sunil Malavasi, Fabio Rustgi, Anil K. TI CD38-Expressing Myeloid-Derived Suppressor Cells Promote Tumor Growth in a Murine Model of Esophageal Cancer SO CANCER RESEARCH LA English DT Article ID CYCLIC ADP-RIBOSE; NITRIC-OXIDE; IMMUNE SUPPRESSION; MOUSE MODEL; CD38; INFLAMMATION; GENE; MICROENVIRONMENT; TRANSCRIPTION; LYMPHOCYTES AB Myeloid-derived suppressor cells (MDSC) are an immunosuppressive population of immature myeloid cells found in advanced-stage cancer patients and mouse tumor models. Production of inducible nitric oxide synthase (iNOS) and arginase, as well as other suppressive mechanisms, allows MDSCs to suppress T-cell-mediated tumor clearance and foster tumor progression. Using an unbiased global gene expression approach in conditional p120-catenin knockout mice (L2-cre; p120ctn(f/f)), a model of oral-esophageal cancer, we have identified CD38 as playing a vital role in MDSC biology, previously unknown. CD38 belongs to the ADP-ribosyl cyclase family and possesses both ectoenzyme and receptor functions. It has been described to function in lymphoid and early myeloid cell differentiation, cell activation, and neutrophil chemotaxis. We find that CD38 expression in MDSCs is evident in other mouse tumor models of esophageal carcinogenesis, and CD38(high) MDSCs are more immature than MDSCs lacking CD38 expression, suggesting a potential role for CD38 in the maturation halt found in MDSC populations. CD38(high) MDSCs also possess a greater capacity to suppress activated T cells, and promote tumor growth to a greater degree than CD38(low) MDSCs, likely as a result of increased iNOS production. In addition, we have identified novel tumor-derived factors, specifically IL6, IGFBP3, and CXCL16, which induce CD38 expression by MDSCs ex vivo. Finally, we have detected an expansion of CD38(+) MDSCs in peripheral blood of advanced-stage cancer patients and validated targeting CD38 in vivo as a novel approach to cancer therapy. (C) 2015 AACR. C1 [Karakasheva, Tatiana A.; Waldron, Todd J.; Hicks, Philip D.; Rustgi, Anil K.] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Karakasheva, Tatiana A.; Waldron, Todd J.; Hicks, Philip D.; Rustgi, Anil K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Eruslanov, Evgeniy; O'Brien, Shaun; Singhal, Sunil] Hosp Univ Penn, Sch Med, Dept Surg, Thorac Surg Res Lab, Philadelphia, PA 19104 USA. [Kim, Sang-Bae; Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Basu, Devraj] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Basu, Devraj; Singhal, Sunil] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. [Malavasi, Fabio] Univ Turin, Dept Med Sci, Sch Med, Lab Immunogenet, Turin, Italy. [Rustgi, Anil K.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Rustgi, AK (reprint author), Univ Penn, 951 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM anil2@mail.med.upenn.edu OI MALAVASI, Fabio/0000-0002-1844-174X FU NIH/NCI [P01-CA098101, U01-CA14305603]; NIH/NIDDK [T32-DK007066]; NIH [F32-CA162719, R01-CA163256-01]; NIH/NIDDK Center for Molecular Studies in Digestive and Liver Diseases [P30-DK050306]; American Cancer Society [RP-10-033-01-CCE]; NIH NIH/NIDCR [K08-DE022842]; Italian Ministry of Education, University and Research (Progetto PRIN); Italian Ministry of Education, University and Research (FIRB); Fondazione Ricerca in Medicina Sperimentale (FIRMS) FX This work was supported by the NIH/NCI grant P01-CA098101 (A.K. Rustgi, T.J. Waldron, T.A. Karakasheva), NIH/NCI grant U01-CA14305603 (A.K. Rustgi), NIH/NIDDK (T32-DK007066 to T. Waldron), NIH (F32-CA162719 to T. Waldron), NIH/NIDDK Center for Molecular Studies in Digestive and Liver Diseases (P30-DK050306), American Cancer Society (RP-10-033-01-CCE), NIH NIH/NIDCR (K08-DE022842 to D. Basu), NIH (Transformative R01-CA163256-01 to S. Singhal), Italian Ministry of Education, University and Research (Progetto PRIN and FIRB to F. Malavasi), and by the Fondazione Ricerca in Medicina Sperimentale (FIRMS; F. Malavasi). NR 49 TC 11 Z9 11 U1 3 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2015 VL 75 IS 19 BP 4074 EP 4085 DI 10.1158/0008-5472.CAN-14-3639 PG 12 WC Oncology SC Oncology GA CU2ES UT WOS:000363336800011 PM 26294209 ER PT J AU Anderson, KC AF Anderson, Kenneth C. TI AACR Cancer Progress Report 2015: Transforming Lives Through Precision Medicine SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Kenneth_anderson@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2015 VL 21 IS 19 BP 4247 EP 4247 DI 10.1158/1078-0432.CCR-15-1978 PG 1 WC Oncology SC Oncology GA CU2CQ UT WOS:000363330500001 PM 26429978 ER PT J AU Wolach, O Stone, RM AF Wolach, Ofir Stone, Richard M. TI Blinatumomab for the Treatment of Philadelphia Chromosome-Negative, Precursor B-cell Acute Lymphoblastic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; SINGLE-CHAIN ANTIBODY; TERM-FOLLOW-UP; ADULT PATIENTS; PHASE-II; BISPECIFIC ANTIBODY; PEDIATRIC-PATIENTS; COMPLETE REMISSION; ENGAGING ANTIBODY AB Blinatumomab is a CD19/CD3 bispescific antibody designed to redirect T cells toward malignant B cells and induce their lysis. It recently gained accelerated approval by the FDA for the treatment of relapsed or refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (RR-ALL). In the phase II trial that served as the basis for approval, blinatumomab demonstrated significant single-agent activity and induced remission [complete remission (CR) and CR with incomplete recovery of peripheral blood counts (CRh)] in 43% of 189 adult patients with RR-ALL; the majority of responders (82%) also attained negative minimal residual disease (MRD ) status that did not generally translate into long-term remissions in most cases. Additional studies show that blinatumomab can induce high response rates associated with lasting remissions in patients in first remission treated for MRD positivity, suggesting a role for blinatumomab in the upfront, MRD-positive setting. Blinatumomab infusion follows a predictable immunopharmacologic profile, including early cytokine release that can be associated with a clinical syndrome, T-cell expansion, and B-cell depletion. Neurologic toxicities represent a unique toxicity that shares similarities with adverse effects of other T-cell engaging therapies. Further studies are needed to clarify the optimal disease setting and timing for blinatumomab therapy. Additional insights into the pathogenesis, risk factors, and prevention of neurologic toxicities as well as a better understanding of the clinical consequences and biologic pathways that are associated with drug resistance are needed. (C) 2015 AACR. C1 [Wolach, Ofir; Stone, Richard M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM rstone@partners.org NR 57 TC 2 Z9 2 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2015 VL 21 IS 19 BP 4262 EP 4269 DI 10.1158/1078-0432.CCR-15-0125 PG 8 WC Oncology SC Oncology GA CU2CQ UT WOS:000363330500006 PM 26283683 ER PT J AU Casper, C Chaturvedi, S Munshi, N Wong, R Qi, M Schaffer, M Bandekar, R Hall, B van de Velde, H Vermeulen, J Reddy, M van Rhee, F AF Casper, Corey Chaturvedi, Shalini Munshi, Nikhil Wong, Raymond Qi, Ming Schaffer, Michael Bandekar, Rajesh Hall, Brett van de Velde, Helgi Vermeulen, Jessica Reddy, Manjula van Rhee, Frits TI Analysis of Inflammatory and Anemia-Related Biomarkers in a Randomized, Double-Blind, Placebo-Controlled Study of Siltuximab (Anti-IL6 Monoclonal Antibody) in Patients With Multicentric Castleman Disease SO CLINICAL CANCER RESEARCH LA English DT Article ID C-REACTIVE PROTEIN; RENAL-CELL CARCINOMA; MULTIPLE-MYELOMA; INTERLEUKIN-6; HEPCIDIN; SPECTRUM; UPDATE; TRIAL AB Purpose: Siltuximab (IL6 antibody) is approved for the treatment of multicentric Castleman disease (MCD). Effects of IL6 inhibition on the inflammatory milieu accompanying MCD have not been characterized. Experimental Design: Trends in inflammatory-and anemia-associated markers, measured over the course of a placebo-controlled study of siltuximab (11 mg/kg q3w) in patients with MCD (n = 79), were characterized. Results: Baseline IL6 and C-reactive protein (CRP) levels were significantly correlated (r = 0.708; P < 0.0001). CRP levels decreased (median, 92%) by cycle 1 day 8 (C1D8), remaining suppressed during siltuximab treatment while remaining stable in the placebo group. There were no associations between baseline CRP or IL6 and MCD symptom burden, histologic subtype, ethnicity, maximum CRP decrease, and response parameters. A hemoglobin response change >= 15 g/L at week 13) was observed with siltuximab (61%; P = 0.0002). Median hepcidin decrease from baseline at C1D8 with siltuximab was 47% versus median 11% increase with placebo. Maximum post-baseline changes in hepcidin levels among siltuximab recipients were correlated with maximum changes for hemoglobin (r = -0.395; P = 0.00607), total iron-binding capacity (TIBC; r = -0.354; P = 0.01694), and ferritin (r = 0.599; P = 0.0001). Greater median changes from baseline in ferritin, hemoglobin, and TIBC were observed in anemic siltuximab-treated patients. Conclusions: IL6 neutralization with siltuximab resulted in sustained CRP suppression and improvement of anemia, in part, by hepcidin pathway inhibition. 2015 AACR. C1 [Casper, Corey] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Chaturvedi, Shalini; Qi, Ming; Schaffer, Michael; Bandekar, Rajesh; Hall, Brett; Reddy, Manjula] Janssen Res & Dev, Spring House, PA USA. [Munshi, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wong, Raymond] Chinese Univ Hong Kong, Prince Wales Hosp, Sir YK Pao Ctr Canc, Hong Kong, Hong Kong, Peoples R China. [van de Velde, Helgi] Janssen Res & Dev, Beerse, Belgium. [Vermeulen, Jessica] Janssen Res & Dev, Leiden, Netherlands. [van Rhee, Frits] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. RP Casper, C (reprint author), Fred Hutchinson Canc Res Ctr, Program Global Oncol, 1100 Fairview Ave North,M1-B140, Seattle, WA 98109 USA. EM ccasper@fhcrc.org FU Janssen Research & Development, LLC. FX This study was supported by Janssen Research & Development, LLC. NR 34 TC 10 Z9 10 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2015 VL 21 IS 19 BP 4294 EP 4304 DI 10.1158/1078-0432.CCR-15-0134 PG 11 WC Oncology SC Oncology GA CU2CQ UT WOS:000363330500010 PM 26124203 ER PT J AU Duran-Struuck, R Huang, CA Orf, K Bronson, RT Sachs, DH Spitzer, TR AF Duran-Struuck, Raimon Huang, Christene A. Orf, Katherine Bronson, Roderick T. Sachs, David H. Spitzer, Thomas R. TI Miniature Swine as a Clinically Relevant Model of Graft-Versus-Host Disease SO COMPARATIVE MEDICINE LA English DT Article ID BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC-CELL TRANSPLANTATION; MISMATCHED RENAL-ALLOGRAFTS; LEUKOCYTE DIFFERENTIATION ANTIGENS; 3RD INTERNATIONAL WORKSHOP; IMMUNOREGULATORY T-CELLS; MINIPIG INBRED LINE; LARGE-ANIMAL-MODEL; CD WORKSHOP; LIVER XENOTRANSPLANTATION AB Miniature swine provide a preclinical model of hematopoietic cell transplantation (HCT) for studies of graft-versus-host disease. HCT between MHC-matched or -mismatched pigs can be performed to mimic clinical scenarios with outcomes that closely resemble those observed in human HCT recipients. With myeloablative conditioning, HCT across MHC barriers is typically fatal, with pigs developing severe (grade III or IV) GVHD involving the gastrointestinal tract, liver, and skin. Unlike rodent models, miniature swine provide an opportunity to perform extended longitudinal studies on individual animals, because multiple tissue biopsies can be harvested without the need for euthanasia. In addition, we have developed a swine GVHD scoring system that parallels that used in the human clinical setting. Given the similarities of GVHD in pigs and humans, we hope that the use of this scoring system facilitates clinical and scientific discourse between the laboratory and the clinic. We anticipate that results of swine studies will support the development of new strategies to improve the identification and treatment of GVHD in clinical HCT scenarios. C1 [Duran-Struuck, Raimon; Huang, Christene A.; Orf, Katherine; Sachs, David H.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Duran-Struuck, Raimon] Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Spitzer, Thomas R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Duran-Struuck, R (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM rdura@upenn.edu FU National Cancer Institute [P01CA111519]; National Institute of Allergy and Infectious Disease [R01AI84657]; National Center for Research Resources [1K01RR024466] FX We acknowledge C06RR020135-01 for the construction of the facility used for the production and maintenance of miniature swine and Novartis far the generous gift of cyclosporine used in these studies. This work was supported in part by grants from the National Cancer Institute (P01CA111519 DHS), the National Institute of Allergy and Infectious Disease (R01AI84657, to CAH), and the National Center for Research Resources (1K01RR024466, to RDS). We would like to thank Dr Philippe Brianceau liar his critical review of the manuscript NR 99 TC 1 Z9 1 U1 0 U2 6 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD OCT PY 2015 VL 65 IS 5 BP 429 EP 443 PG 15 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA CT8VV UT WOS:000363095900008 PM 26473348 ER PT J AU Weisbord, SD Palevsky, PM AF Weisbord, Steven D. Palevsky, Paul M. TI Contrast-associated Acute Kidney Injury SO CRITICAL CARE CLINICS LA English DT Article DE Contrast; Acute kidney injury; Nephrotoxin; Prevention; latrogenic ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE-RENAL-FAILURE; RANDOMIZED CONTROLLED-TRIAL; GLOMERULAR-FILTRATION-RATE; RADIOCONTRAST-INDUCED NEPHROPATHY; GELATINASE-ASSOCIATED LIPOCALIN; LONG-TERM MORTALITY; HIGH-RISK PATIENTS; SODIUM-BICARBONATE; CARDIAC ANGIOGRAPHY AB Contrast-associated acute kidney injury (CAAKI) is a common iatrogenic condition. The principal risk factors for CAAKI are underlying renal impairment, diabetes in the setting of kidney disease, and intravascular volume depletion, effective or absolute. CAAKI is associated with serious adverse short-term and long-term outcomes, including mortality and more rapidly progressive chronic kidney disease, although the causal nature of these associations remains unproved. Patients with chronic kidney disease and other risk factors for CAAKI who present with acute coronary syndrome should undergo indicated angiographic procedures. C1 [Weisbord, Steven D.; Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Room 7E120 111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 75 TC 1 Z9 1 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0704 EI 1557-8232 J9 CRIT CARE CLIN JI Crit. Care Clin. PD OCT PY 2015 VL 31 IS 4 BP 725 EP + DI 10.1016/j.ccc.2015.06.008 PG 12 WC Critical Care Medicine SC General & Internal Medicine GA CU3OK UT WOS:000363434500009 PM 26410140 ER PT J AU Kopans, DB AF Kopans, D. B. TI Breast cancer screening panels continue to confuse the facts and inject their own biases SO CURRENT ONCOLOGY LA English DT Editorial Material ID CARCINOMA MORTALITY; MAMMOGRAPHY; WOMEN; REDUCTION; IMPACT; GUIDELINES; BENEFITS; PROGRAM; SCIENCE; TRIALS C1 Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, Avon Comprehens Breast Ctr, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, Avon Comprehens Breast Ctr, Suite 240,15 Parkman St, Boston, MA 02114 USA. EM kopans.daniel@mgh.harvard.edu NR 44 TC 4 Z9 4 U1 0 U2 1 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1198-0052 J9 CURR ONCOL JI Curr. Oncol. PD OCT PY 2015 VL 22 IS 5 BP E376 EP E379 DI 10.3747/co.22.2880 PG 4 WC Oncology SC Oncology GA CU1YI UT WOS:000363317900010 PM 26628879 ER PT J AU Criscitiello, C Giuliano, M Curigliano, G De Laurentiis, M Arpino, G Carlomagno, N De Placido, S Golshan, M Santangelo, M AF Criscitiello, C. Giuliano, M. Curigliano, G. De Laurentiis, M. Arpino, G. Carlomagno, N. De Placido, S. Golshan, M. Santangelo, M. TI Surgery of the primary tumor in de novo metastatic breast cancer: To do or not to do? SO EJSO LA English DT Review DE Primary metastatic breast cancer; Surgery; Survival ID RANDOMIZED CONTROLLED-TRIAL; STAGE-IV DISEASE; SURGICAL REMOVAL; INITIAL PRESENTATION; DISTANT METASTASES; IMPROVED SURVIVAL; SYSTEMIC THERAPY; IMPROVE SURVIVAL; INTACT PRIMARY; RESECTION AB Approximately five percent of all breast cancer patients in developed countries present with distant metastases at initial diagnosis. Due to its incurability, metastatic breast cancer is generally treated with systemic therapies to achieve disease control and reduce tumor-related symptoms. Primary treatments for metastatic breast cancer are chemotherapy, endocrine- and biologic therapy, whereas surgery with or without radiotherapy is usually performed to treat impending wound issues. Since 2002, several retrospective non-randomized clinical studies have shown that extirpation of the primary tumor correlates with a significantly improved survival in patients with primary metastatic breast cancer. Others have argued that this survival benefit associated with surgery may be due to selection biases. Therefore, in the absence of published results from randomized controlled trials carried out in India and Turkey and completion of a trial in the United States, there is no clear conclusion on whether surgical excision of the primary breast cancer translates into a survival benefit for patients with de novo metastatic disease. Furthermore, timing and type of surgical procedure, as well as selection of patients who could benefit the most from this approach, represent additional points of uncertainty. Despite the epidemiological burden of this condition, there are no guidelines on how to manage breast cancer patients presenting with de novo metastatic breast cancer; and decisions are often left to provider and patient preferences. Here, we present a critical overview of the literature focusing on the rationale and potential role of primary tumour excision in patients with de novo metastatic breast cancer. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Criscitiello, C.; Curigliano, G.] European Inst Oncol, Div Expt Canc Med, Milan, Italy. [Giuliano, M.] Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy. [Giuliano, M.] Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. [De Laurentiis, M.] IRCCS Fdn Pascale, Ist Nazl Tumori, Med Oncol, Naples, Italy. [Arpino, G.; De Placido, S.] Azienda Osped Univ Federico II, Med Oncol, Naples, Italy. [Carlomagno, N.; Santangelo, M.] Univ Naples Federico II, Dept Adv Biomed Sci, Gen Surg, Naples, Italy. [Golshan, M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Golshan, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Santangelo, M (reprint author), Univ Naples Federico II, Dept Adv Biomed Sci, Gen Surg, Naples, Italy. EM michele.santangelo@unina.it OI Santangelo, Michele/0000-0003-3046-9988 NR 44 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0748-7983 EI 1532-2157 J9 EJSO-EUR J SURG ONC JI EJSO PD OCT PY 2015 VL 41 IS 10 BP 1288 EP 1292 DI 10.1016/j.ejso.2015.07.013 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA CU2HW UT WOS:000363345600003 PM 26238477 ER PT J AU Frank, MB Hsu, J Landrum, MB Chernew, ME AF Frank, Matthew B. Hsu, John Landrum, Mary Beth Chernew, Michael E. TI The Impact of a Tiered Network on Hospital Choice SO HEALTH SERVICES RESEARCH LA English DT Article DE Tiered network; cost sharing; hospital choice ID HEALTH-INSURANCE EXPERIMENT; MEDICATION ADHERENCE; CONTROLLED-TRIAL; DESIGN PROGRAM; CARE; PLANS; SERVICES; MAMMOGRAPHY; COPAYMENTS; COVERAGE AB Objective. To evaluate the effect of a tiered network on hospital choice for scheduled admissions. Data. The 2009-2012 patient-level claims data from Blue Cross Blue Shield of Massachusetts (BCBSMA). Study Design. BCBSMA's three-tiered hospital network employs large differential cost sharing to encourage patients to seek care at hospitals on the preferred tier. During the study period, 44 percent of hospitals were moved to a different tier based on changes in cost or quality performance. We relied on this longitudinal variation for identification and specified conditional logit models to estimate the effect of the tiered network (TN) on patients' hospital choices relative to a non-TN comparison group. Principal Findings. The TN was associated with increased use of hospitals on the preferred and middle tiers relative to the nonpreferred tier for planned admissions. The results suggest that if all members were in a TN plan, relative to all members being in a non-TN plan, scheduled admissions to hospitals on the nonpreferred tier would drop by 7.6 percentage points, while those to middle and preferred tier hospitals would rise by 0.9 and 6.6 percentage points, respectively. Conclusion. Differential cost sharing can steer patients toward preferred hospitals for planned admissions. C1 [Frank, Matthew B.] Harvard Univ, Sch Law, Grad Sch Arts & Sci, Program Hlth Policy, Cambridge, MA 02138 USA. [Hsu, John] Massachusetts Gen Hosp, Program Clin Econ & Policy Anal, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Landrum, Mary Beth; Chernew, Michael E.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Frank, MB (reprint author), Harvard Univ, Sch Law, Grad Sch Arts & Sci, Program Hlth Policy, 14 Story St,4th Floor, Cambridge, MA 02138 USA. EM frank2@fas.harvard.edu FU Commonwealth Fund; National Science Foundation [DGE-1144152] FX Joint Acknowledgment/Disclosure Statement: We are grateful for helpful comments received from Dana Safran, Angela Li, Wei Ying, and Lulu Liu of Blue Cross Blue Shield of Massachusetts, and Amitabh Chandra, Norman Daniels, Niteesh Choudhry, Tom McGuire, Daria Pelech, Aaron Schwartz, Jacob Wallace, Craig White, Simo Goshev, and participants at the AcademyHealth Annual Research Meeting and the Harvard Medical School Health Economics Seminar. We also thank Yanmei Liu for research assistance. Blue Cross Blue Shield of Massachusetts provided data for the study. The study was supported by a grant from the Commonwealth Fund. Funding for M. B. F. was also provided by the National Science Foundation (Graduate Research Fellowship Program; grant no. DGE-1144152). NR 48 TC 3 Z9 3 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2015 VL 50 IS 5 BP 1628 EP 1648 DI 10.1111/1475-6773.12291 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CT8JX UT WOS:000363063300014 PM 25752219 ER PT J AU Fernandez-Godino, R Garland, DL Pierce, EA AF Fernandez-Godino, Rosario Garland, Donita L. Pierce, Eric A. TI A local complement response by RPE causes early-stage macular degeneration SO HUMAN MOLECULAR GENETICS LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; NONLETHAL OXIDANT INJURY; HUMAN BRUCHS MEMBRANE; EXTRACELLULAR-MATRIX; IN-VITRO; DRUSEN FORMATION; METALLOPROTEINASE ACTIVITY; ABERRANT ACCUMULATION; MALATTIA LEVENTINESE; CELLS AB Inherited and age-related macular degenerations (AMDs) are important causes of vision loss. An early hallmark of these disorders is the formation of sub-retinal pigment epithelium (RPE) basal deposits. A role for the complement system in MDs was suggested by genetic association studies, but direct functional connections between alterations in the complement system and the pathogenesis of MD remain to be defined. We used primary RPE cells from a mouse model of inherited MD due to a p.R345W mutation in EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) to investigate the role of the RPE in early MD pathogenesis. Efemp1(R345W) RPE cells recapitulate the basal deposit formation observed in vivo by producing sub-RPE deposits in vitro. The deposits share features with basal deposits, and their formation was mediated by EFEMP1(R345W) or complement component 3a (C3a), but not by complement component 5a (C5a). Increased activation of complement appears to occur in response to an abnormal extracellular matrix (ECM), generated by the mutant EFEMP1(R345W) protein and reduced ECM turnover due to inhibition of matrix metalloproteinase 2 by EFEMP1(R345W) and C3a. Increased production of C3a also stimulated the release of cytokines such as interleukin (IL)-6 and IL-1B, which appear to have a role in deposit formation, albeit downstream of C3a. These studies provide the first direct indication that complement components produced locally by the RPE are involved in the formation of basal deposits. Furthermore, these results suggest that C3a generated by RPE is a potential therapeutic target for the treatment of EFEMP1-associated MD as well as AMD. C1 [Fernandez-Godino, Rosario; Garland, Donita L.; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst,Dept Ophthalmol, Boston, MA USA. [Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab,Study Retinal Degenerat,Dept Opht, Boston, MA USA. RP Pierce, EA (reprint author), Massachusetts Eye & Ear Infirm, Ocular Genom Inst, 243 Charles St, Boston, MA 02114 USA. EM eric_pierce@meei.harvard.edu OI Pierce, Eric/0000-0002-2354-4102 FU Ocular Genomics Institute; National Eye Institute [P30EY003790] FX This work was supported by the Ocular Genomics Institute. The TEM work was supported in part by a National Eye Institute Core grant (P30EY003790). NR 85 TC 5 Z9 5 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2015 VL 24 IS 19 BP 5555 EP 5569 DI 10.1093/hmg/ddv287 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CT7TT UT WOS:000363018100014 PM 26199322 ER PT J AU Al Olama, AA Dadaev, T Hazelett, DJ Li, QY Leongamornlert, D Saunders, EJ Stephens, S Cieza-Borrella, C Whitmore, I Garcia, SB Giles, GG Southey, MC Fitzgerald, L Gronberg, H Wiklund, F Aly, M Henderson, BE Schumacher, F Haiman, CA Schleutker, J Wahlfors, T Tammela, TL Nordestgaard, BG Key, TJ Travis, RC Neal, DE Donovan, JL Hamdy, FC Pharoah, P Pashayan, N Khaw, KT Stanford, JL Thibodeau, SN Mcdonnell, SK Schaid, DJ Maier, C Vogel, W Luedeke, M Herkommer, K Kibel, AS Cybulski, C Wokolorczyk, D Kluzniak, W Cannon-Albright, L Brenner, H Butterbach, K Arndt, V Park, JY Sellers, T Lin, HY Slavov, C Kaneva, R Mitev, V Batra, J Clements, JA Spurdle, A Teixeira, MR Paulo, P Maia, S Pandha, H Michael, A Kierzek, A Govindasami, K Guy, M Lophatonanon, A Muir, K Vinuela, A Brown, AA Freedman, M Conti, DV Easton, D Coetzee, GA Eeles, RA Kote-Jarai, Z AF Al Olama, Ali Amin Dadaev, Tokhir Hazelett, Dennis J. Li, Qiuyan Leongamornlert, Daniel Saunders, Edward J. Stephens, Sarah Cieza-Borrella, Clara Whitmore, Ian Garcia, Sara Benlloch Giles, Graham G. Southey, Melissa C. Fitzgerald, Liesel Gronberg, Henrik Wiklund, Fredrik Aly, Markus Henderson, Brian E. Schumacher, Fredrick Haiman, Christopher A. Schleutker, Johanna Wahlfors, Tiina Tammela, Teuvo L. Nordestgaard, Borge G. Key, Tim J. Travis, Ruth C. Neal, David E. Donovan, Jenny L. Hamdy, Freddie C. Pharoah, Paul Pashayan, Nora Khaw, Kay-Tee Stanford, Janet L. Thibodeau, Stephen N. Mcdonnell, Shannon K. Schaid, Daniel J. Maier, Christiane Vogel, Walther Luedeke, Manuel Herkommer, Kathleen Kibel, Adam S. Cybulski, Cezary Wokolorczyk, Dominika Kluzniak, Wojciech Cannon-Albright, Lisa Brenner, Hermann Butterbach, Katja Arndt, Volker Park, Jong Y. Sellers, Thomas Lin, Hui-Yi Slavov, Chavdar Kaneva, Radka Mitev, Vanio Batra, Jyotsna Clements, Judith A. Spurdle, Amanda Teixeira, Manuel R. Paulo, Paula Maia, Sofia Pandha, Hardev Michael, Agnieszka Kierzek, Andrzej Govindasami, Koveela Guy, Michelle Lophatonanon, Artitaya Muir, Kenneth Vinuela, Ana Brown, Andrew A. Freedman, Mathew Conti, David V. Easton, Douglas Coetzee, Gerhard A. Eeles, Rosalind A. Kote-Jarai, Zsofia CA PRACTICAL Consortium COGS-CRUK GWAS-ELLIPSE Part GAME-O Australian Prostate Canc BioResour UK Genetic Prostate Canc Study Col UK ProtecT Study Collaborators TI Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ANDROGEN RECEPTOR; GENE-EXPRESSION; BREAST-CANCER; HNF1B GENE; VARIANTS; NGEP; PREDISPOSITION; TRANSCRIPTOME; METAANALYSIS AB Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain similar to 38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region. C1 [Al Olama, Ali Amin; Garcia, Sara Benlloch; Easton, Douglas] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Dept Oncol, Cambridge CB2 2QQ, England. [Pharoah, Paul; Pashayan, Nora] Univ Cambridge, Dept Oncol, Strangeways Lab, Ctr Canc Genet Epidemiol, Cambridge, England. [Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge, England. [Dadaev, Tokhir; Leongamornlert, Daniel; Saunders, Edward J.; Stephens, Sarah; Cieza-Borrella, Clara; Whitmore, Ian; Govindasami, Koveela; Guy, Michelle; Eeles, Rosalind A.; Kote-Jarai, Zsofia] Inst Canc Res & Royal Marsden NHS Fdn Trust, Div Genet & Epidemiol, London, England. [Hazelett, Dennis J.; Conti, David V.; Coetzee, Gerhard A.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Urol, Los Angeles, CA 90033 USA. [Hazelett, Dennis J.; Henderson, Brian E.; Schumacher, Fredrick; Haiman, Christopher A.; Conti, David V.; Coetzee, Gerhard A.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Li, Qiuyan] Xiamen Univ, Coll Med, Xiamen, Peoples R China. [Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Parkville, Vic 3052, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia. [Fitzgerald, Liesel] Tissupath Pty Ltd, Melbourne, Vic, Australia. [Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Aly, Markus] Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden. [Schleutker, Johanna] Univ Turku, Dept Med Biochem, Turku, Finland. [Schleutker, Johanna] Univ Turku, Genet Inst Biomed, Turku, Finland. [Schleutker, Johanna; Wahlfors, Tiina] Univ Tampere, BioMediTech, FIN-33101 Tampere, Finland. [Schleutker, Johanna; Wahlfors, Tiina] FimLab Labs, Tampere, Finland. [Tammela, Teuvo L.] Univ Tampere, Dept Urol, Tampere Univ Hosp, FIN-33101 Tampere, Finland. [Tammela, Teuvo L.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark. [Nordestgaard, Borge G.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark. [Key, Tim J.; Travis, Ruth C.] Univ Oxford, John Radcliffe Hosp, Canc Epidemiol, Nuffield Dept Populat Hlth, Oxford OX3 9DU, England. [Hamdy, Freddie C.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg Sci, Oxford OX3 9DU, England. [Hamdy, Freddie C.] Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Oxford OX3 9DU, England. [Neal, David E.] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge, England. [Donovan, Jenny L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Pashayan, Nora] UCL, Dept Appl Hlth Res, London, England. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Thibodeau, Stephen N.; Mcdonnell, Shannon K.; Schaid, Daniel J.] Mayo Clin, Rochester, MN USA. [Maier, Christiane; Luedeke, Manuel] Univ Hosp Ulm, Dept Urol, Ulm, Germany. [Vogel, Walther] Univ Ulm, Inst Human Genet, D-89069 Ulm, Germany. [Herkommer, Kathleen] Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-80290 Munich, Germany. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg, Boston, MA 02115 USA. [Cybulski, Cezary; Wokolorczyk, Dominika; Kluzniak, Wojciech] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [Cannon-Albright, Lisa] Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA. [Cannon-Albright, Lisa] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA. [Brenner, Hermann; Butterbach, Katja; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann; Butterbach, Katja] German Canc Consortium DKTK, Heidelberg, Germany. [Park, Jong Y.; Sellers, Thomas] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. [Lin, Hui-Yi] H Lee Moffitt Canc Ctr & Res Inst, Biostat Program, Tampa, FL USA. [Slavov, Chavdar] Med Univ Sofia, Dept Urol, Sofia, Bulgaria. [Slavov, Chavdar] Med Univ Sofia, Alexandrovska Univ Hosp, Sofia, Bulgaria. [Kaneva, Radka; Mitev, Vanio] Med Univ Sofia, Mol Med Ctr, Dept Med Chem & Biochem, Sofia, Bulgaria. [Batra, Jyotsna; Clements, Judith A.] Queensland Univ Technol, Australian Prostate Canc Res Ctr Qld, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Batra, Jyotsna; Clements, Judith A.] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld 4001, Australia. [Spurdle, Amanda] Queensland Inst Med Res, Mol Canc Epidemiol Lab, Brisbane, Qld 4006, Australia. [Teixeira, Manuel R.; Paulo, Paula; Maia, Sofia] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4100 Oporto, Portugal. [Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej] Univ Surrey, Guildford GU2 5XH, Surrey, England. [Lophatonanon, Artitaya; Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England. [Lophatonanon, Artitaya; Muir, Kenneth] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Vinuela, Ana] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. [Brown, Andrew A.] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, NORMENT, Oslo, Norway. [Brown, Andrew A.] Univ Geneva, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland. [Freedman, Mathew] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kote-Jarai, Z (reprint author), Inst Canc Res & Royal Marsden NHS Fdn Trust, Div Genet & Epidemiol, London, England. EM zsofia.kote-jarai@icr.ac.uk RI Paulo, Paula/F-1441-2016; Teixeira, Manuel/E-4885-2011; Batra, Jyotsna/B-4130-2011; Brenner, Hermann/B-4627-2017; OI Evans, Gareth/0000-0002-8482-5784; Arndt, Volker/0000-0001-9320-8684; albright, lisa/0000-0003-2602-3668; Giles, Graham/0000-0003-4946-9099; Paulo, Paula/0000-0001-8387-2127; Teixeira, Manuel/0000-0002-4896-5982; Clements, Judith/0000-0001-6026-1964; Brenner, Hermann/0000-0002-6129-1572; Kierzek, Andrzej/0000-0002-2605-9057; Vinuela, Ana/0000-0003-3771-8537; Eeles, Rosalind/0000-0002-3698-6241; Leongamornlert, Daniel/0000-0002-3486-3168 FU European Commission [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK [C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135]; National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative [1 U19 CA 148537-01]; Institute of Cancer Research FX This work was supported by European Commission's Seventh Framework Programme grant agreement No. 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135 and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA 148537-01 (the GAME-ON initiative). Funding to pay the Open Access publication charges for this article was provided by the Institute of Cancer Research. NR 62 TC 12 Z9 12 U1 5 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2015 VL 24 IS 19 BP 5589 EP 5602 DI 10.1093/hmg/ddv203 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CT7TT UT WOS:000363018100017 ER PT J AU Han, Y Hazelett, DJ Wiklund, F Schumacher, FR Stram, DO Berndt, SI Wang, ZM Rand, KA Hoover, RN Machiela, MJ Yeager, M Burdette, L Chung, CC Hutchinson, A Yu, K Xu, JF Travis, RC Key, TJ Siddiq, A Canzian, F Takahashi, A Kubo, M Stanford, JL Kolb, S Gapstur, SM Diver, WR Stevens, VL Strom, SS Pettaway, CA Al Olama, AA Kote-Jarai, Z Eeles, RA Yeboah, ED Tettey, Y Biritwum, RB Adjei, AA Tay, E Truelove, A Niwa, S Chokkalingam, AP Isaacs, WB Chen, C Lindstrom, S Le Marchand, L Giovannucci, EL Pomerantz, M Long, H Li, FG Ma, J Stampfer, M John, EM Ingles, SA Kittles, RA Murphy, AB Blot, WJ Signorello, LB Zheng, W Albanes, D Virtamo, J Weinstein, S Nemesure, B Carpten, J Leske, MC Wu, SY Hennis, AJM Rybicki, BA Neslund-Dudas, C Hsing, AW Chu, LS Goodman, PJ Klein, EA Zheng, SL Witte, JS Casey, G Riboli, E Li, QY Freedman, ML Hunter, DJ Gronberg, H Cook, MB Nakagawa, H Kraft, P Chanock, SJ Easton, DF Henderson, BE Coetzee, GA Conti, DV Haiman, CA AF Han, Ying Hazelett, Dennis J. Wiklund, Fredrik Schumacher, Fredrick R. Stram, Daniel O. Berndt, Sonja I. Wang, Zhaoming Rand, Kristin A. Hoover, Robert N. Machiela, Mitchell J. Yeager, Merideth Burdette, Laurie Chung, Charles C. Hutchinson, Amy Yu, Kai Xu, Jianfeng Travis, Ruth C. Key, Timothy J. Siddiq, Afshan Canzian, Federico Takahashi, Atsushi Kubo, Michiaki Stanford, Janet L. Kolb, Suzanne Gapstur, Susan M. Diver, W. Ryan Stevens, Victoria L. Strom, Sara S. Pettaway, Curtis A. Al Olama, Ali Amin Kote-Jarai, Zsofia Eeles, Rosalind A. Yeboah, Edward D. Tettey, Yao Biritwum, Richard B. Adjei, Andrew A. Tay, Evelyn Truelove, Ann Niwa, Shelley Chokkalingam, Anand P. Isaacs, William B. Chen, Constance Lindstrom, Sara Le Marchand, Loic Giovannucci, Edward L. Pomerantz, Mark Long, Henry Li, Fugen Ma, Jing Stampfer, Meir John, Esther M. Ingles, Sue A. Kittles, Rick A. Murphy, Adam B. Blot, William J. Signorello, Lisa B. Zheng, Wei Albanes, Demetrius Virtamo, Jarmo Weinstein, Stephanie Nemesure, Barbara Carpten, John Leske, M. Cristina Wu, Suh-Yuh Hennis, Anselm J. M. Rybicki, Benjamin A. Neslund-Dudas, Christine Hsing, Ann W. Chu, Lisa Goodman, Phyllis J. Klein, Eric A. Zheng, S. Lilly Witte, John S. Casey, Graham Riboli, Elio Li, Qiyuan Freedman, Matthew L. Hunter, David J. Gronberg, Henrik Cook, Michael B. Nakagawa, Hidewaki Kraft, Peter Chanock, Stephen J. Easton, Douglas F. Henderson, Brian E. Coetzee, Gerhard A. Conti, David V. Haiman, Christopher A. TI Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions SO HUMAN MOLECULAR GENETICS LA English DT Article ID RISK-ASSOCIATED LOCI; WIDE ASSOCIATION; CAUSAL VARIANTS; TRANSETHNIC METAANALYSIS; SEQUENCE VARIANTS; GENE-EXPRESSION; ANALYSES REVEAL; COMMON VARIANT; MULTIPLE; IDENTIFICATION AB Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 x 10(-4)-5.6 x 10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 x 10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation. C1 [Han, Ying; Hazelett, Dennis J.; Schumacher, Fredrick R.; Stram, Daniel O.; Rand, Kristin A.; Ingles, Sue A.; Casey, Graham; Henderson, Brian E.; Coetzee, Gerhard A.; Conti, David V.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Schumacher, Fredrick R.; Stram, Daniel O.; Ingles, Sue A.; Casey, Graham; Henderson, Brian E.; Coetzee, Gerhard A.; Conti, David V.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Coetzee, Gerhard A.] Univ So Calif, Keck Sch Med, Dept Urol, Los Angeles, CA 90033 USA. [Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Berndt, Sonja I.; Wang, Zhaoming; Hoover, Robert N.; Machiela, Mitchell J.; Burdette, Laurie; Chung, Charles C.; Hutchinson, Amy; Yu, Kai; Albanes, Demetrius; Weinstein, Stephanie; Cook, Michael B.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Wang, Zhaoming; Yeager, Merideth; Burdette, Laurie; Hutchinson, Amy] SAIC Frederick Inc, NCI DCEG, Canc Genom Res Lab, Frederick, MD USA. [Xu, Jianfeng] NorthShore Univ HealthSyst, Program Personalized Canc Care, Evanston, IL USA. [Xu, Jianfeng] NorthShore Univ HealthSyst, Dept Surg, Evanston, IL USA. [Travis, Ruth C.; Key, Timothy J.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England. [Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany. [Takahashi, Atsushi] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Tokyo, Japan. [Kubo, Michiaki] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Tokyo, Japan. [Nakagawa, Hidewaki] RIKEN Ctr Integrat Med Sci, Lab Genome Sequencing Anal, Tokyo, Japan. [Stanford, Janet L.; Kolb, Suzanne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Gapstur, Susan M.; Diver, W. Ryan; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Pettaway, Curtis A.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Al Olama, Ali Amin; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Kote-Jarai, Zsofia; Eeles, Rosalind A.] Inst Canc Res, London SW3 6JB, England. [Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, London, England. [Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, Sutton, Surrey, England. [Yeboah, Edward D.; Tettey, Yao; Biritwum, Richard B.; Adjei, Andrew A.; Tay, Evelyn] Korle Bu Teaching Hosp, Accra, Ghana. [Yeboah, Edward D.; Tettey, Yao; Biritwum, Richard B.; Adjei, Andrew A.; Tay, Evelyn] Univ Ghana, Sch Med, Accra, Ghana. [Truelove, Ann; Niwa, Shelley] WESTAT Corp, Rockville, MD 20850 USA. [Chokkalingam, Anand P.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Isaacs, William B.] Johns Hopkins Univ Hosp, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. [Isaacs, William B.] Inst Med, Baltimore, MD USA. [Chen, Constance; Lindstrom, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.; Stampfer, Meir; Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Pomerantz, Mark; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Long, Henry; Li, Fugen] Dana Farber Canc Inst, Dept Med Oncol, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Ma, Jing] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med,Dept Med, Boston, MA USA. [John, Esther M.; Hsing, Ann W.; Chu, Lisa] Canc Prevent Inst Calif, Fremont, CA USA. [John, Esther M.; Hsing, Ann W.; Chu, Lisa] Stanford Univ, Div Epidemiol, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [John, Esther M.; Hsing, Ann W.; Chu, Lisa] Stanford Univ, Stanford Canc Inst, Sch Med, Stanford, CA 94305 USA. [Kittles, Rick A.] Univ Arizona, Coll Med, Tucson, AZ USA. [Kittles, Rick A.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Murphy, Adam B.] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA. [Blot, William J.] Int Epidemiol Inst, Rockville, MD USA. [Blot, William J.; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Nemesure, Barbara; Leske, M. Cristina; Wu, Suh-Yuh; Hennis, Anselm J. M.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Carpten, John] Translat Genom Res Inst, Phoenix, AZ USA. [Hennis, Anselm J. M.] Univ W Indies, Chron Dis Res Ctr, Bridgetown, Barbados. [Hennis, Anselm J. M.] Univ W Indies, Fac Med Sci, Bridgetown, Barbados. [Rybicki, Benjamin A.; Neslund-Dudas, Christine] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA. [Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98104 USA. [Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Dept Urol, Cleveland, OH 44106 USA. [Zheng, S. Lilly] Wake Forest Sch Med, Ctr Canc Genom, Winston Salem, NC USA. [Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Witte, John S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Li, Qiyuan] Xiamen Univ, Coll Med, Xiamen 361102, Peoples R China. RP Haiman, CA (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. EM haiman@usc.edu RI Cook, Michael/A-5641-2009; Kubo, Michiaki/N-7947-2015 OI Eeles, Rosalind/0000-0002-3698-6241; Machiela, Mitchell/0000-0001-6538-9705; Cook, Michael/0000-0002-0533-7302; FU National Institutes of Health (NIH), National Cancer Institute (NCI) GAME-ON U19 initiative for prostate cancer (ELLIPSE) [CA148537]; NIH/NCI [U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758]; NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics; NIH; NCI; U.S. Public Health Service from the NCI, Department of Health and Human Services [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C]; Cancer Risk Prediction Center (CRisP); Linneus Centre - Swedish Research Council [70867902, K2010-70X-20430-04-3]; Swedish Cancer Foundation [09-0677]; Hedlund Foundation; Soderberg Foundation; Enqvist Foundation; Stockholm County Council; Stiftelsen Johanna Hagstrand och Sigfrid Linner's Minne; Karlsson's Fund for urological and surgical research; NIH [CA63464, CA54281, CA1326792, CA148085, HG004726, CA056678, CA082664, CA092579, ES011126, S06GM08016, CA092447, CA098758]; Division of Cancer Epidemiology and Genetics, NCI, NIH; Cancer Research Fund [99-00524V-10258]; Department of Health Services Cancer Research Program [97-12013, 98-00924V]; NCI, NIH, Department of Health and Human Services [N01-PC-35139]; California Department of Health Services [103885]; Centers for Disease Control and Prevention [1U58DP000807-3]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute; DOD [W81XWH-07-1-0122, DAMD W81XWH-07-1-0203, DAMD W81XWH-06-1-0066, W81XWH-10-1-0532]; American Cancer Society; Public Health Service from the National Cancer Institute [CA37429, 5UM1CA182883]; National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC); NIH/National Human Genome Research Institute [U01 HG004726-01]; Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government; Princess Takamatsu Cancer Research Fund; Takeda Science Foundation; [CA136924]; [CA68578]; [ES007784]; [DAMD W81XWH-07-1-0645]; [CA140388]; [U01 HG004446]; [R01 CA136924]; [R01 GM107427] FX This work was supported by the National Institutes of Health (NIH), National Cancer Institute (NCI) GAME-ON U19 initiative for prostate cancer (ELLIPSE, CA148537). The BPC3 was supported by NIH/NCI cooperative agreements U01-CA98233 to D.J.H., U01-CA98710 to S.M.G., U01-CA98216 to E.R., and U01-CA98758 to B.E.H., and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics). ATBC, PEGASUS/PLCO and the Ghana Prostate Study were supported in part by the Intramural Research Program of the NIH and NCI. Additionally, this research was supported by U.S. Public Health Service contracts N01-CN-45165, N01-RC-45035, N01-RC-37004 and HHSN261201000006C from the NCI, Department of Health and Human Services. CAPS was supported by the Cancer Risk Prediction Center (CRisP; www.crispcenter.org), a Linneus Centre (Contract ID 70867902) financed by the Swedish Research Council (grant no. K2010-70X-20430-04-3), the Swedish Cancer Foundation (grant no. 09-0677), the Hedlund Foundation, the Soderberg Foundation, the Enqvist Foundation, ALF funds from the Stockholm County Council. Stiftelsen Johanna Hagstrand och Sigfrid Linner's Minne, Karlsson's Fund for urological and surgical research. The AAPC studies were supported as follows: The MEC and the genotyping in AAPC were supported by NIH grants CA63464, CA54281, CA1326792, CA148085 and HG004726. Functional annotation was supported by grant CA136924. Genotyping of the PLCO samples was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH. LAAPC was funded by grant 99-00524V-10258 from the Cancer Research Fund, under Interagency Agreement #97-12013 (University of California contract # 98-00924V) with the Department of Health Services Cancer Research Program. Cancer incidence data for the MEC and LAAPC studies have been collected by the Los Angeles Cancer Surveillance Program of the University of Southern California with Federal funds from the NCI, NIH, Department of Health and Human Services, under Contract No. N01-PC-35139, and the California Department of Health Services as part of the state-wide cancer reporting program mandated by California Health and Safety Code Section 103885, and grant number 1U58DP000807-3 from the Centers for Disease Control and Prevention. KCPCS was supported by NIH grants CA056678, CA082664 and CA092579, with additional support from the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute. MDA was support by grants, CA68578, ES007784, DAMD W81XWH-07-1-0645, and CA140388. GECAP was supported by NIH grant ES011126. CaP Genes was supported by CA88164 and CA127298. IPCG was support by DOD grant W81XWH-07-1-0122. DCPC was supported by NIH grant S06GM08016 and DOD grants DAMD W81XWH-07-1-0203, DAMD W81XWH-06-1-0066 and DOD W81XWH-10-1-0532. CPS-II is supported by the American Cancer Society. SELECT is funded by Public Health Service grants CA37429 and 5UM1CA182883 from the National Cancer Institute. SCCS is funded by NIH grant CA092447. SCCS sample preparation was conducted at the Epidemiology Biospecimen Core Lab that is supported in part by the Vanderbilt Ingram Cancer Center (CA68485).; Data on SCCS cancer cases used in this publication were provided by the Alabama Statewide Cancer Registry; Kentucky Cancer Registry; Tennessee Department of Health, Office of Cancer Surveillance; Florida Cancer Data System; North Carolina Central Cancer Registry, North Carolina Division of Public Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor Registry; Mississippi Cancer Registry; South Carolina Central Cancer Registry; Virginia Department of Health, Virginia Cancer Registry; Arkansas Department of Health, Cancer Registry. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Mississippi Cancer Registry. JAPC and LAPC were supported by NIH grants CA63464, CA54281 and CA098758, the NIH/National Human Genome Research Institute by U01 HG004726-01 and the Genome Coordinating Center was supported by U01 HG004446. BBJ was supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government, and this study was supported in part by the Princess Takamatsu Cancer Research Fund and Takeda Science Foundation Award (to H.N.). G.A. Coetzee was supported by grant R01 CA136924 and M.L. Freedman was supported by grant R01 GM107427. We should like to thank all of the men who took part in these studies. NR 78 TC 7 Z9 7 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2015 VL 24 IS 19 BP 5603 EP 5618 DI 10.1093/hmg/ddv269 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CT7TT UT WOS:000363018100018 PM 26162851 ER PT J AU Sabet, H Stack, BC Nagarkar, VV AF Sabet, Hamid Stack, Brendan C., Jr. Nagarkar, Vivek V. TI A Hand-Held, Intra-Operative Positron Imaging Probe for Surgical Applications SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE Handheld; hybrid scintillator; imaging positron probe; intra-operative; pulse shape discrimination; SiPM ID GUIDED SURGERY; BETA-PROBE; HIGH-RESOLUTION; RAY CAMERA; PERFORMANCE; DETECTOR; SYSTEM; CANCER; SCINTILLATORS; LOCALIZATION AB We have developed a prototype intra-operative beta(+) imaging probe to help tumor removal and malignant tissue resection. The probe can be used during surgery to provide clear delineation of malignant tissues. Our probe consists of a hybrid scintillator coupled to a silicon photomultiplier (SiPM) array with associated front-end electronics encapsulated in an ergonomic aluminum housing. Pulse shape discrimination electronics has been implemented and integrated into the downstream data acquisition system. The field of view of the probe is 10 x 10 mm(2) realized by a 0.4 mm thick CsI:Tl scintillator coupled to a 1 mm thick LYSO. While CsI:Tl layer acts as beta(+) sensitive detector, LYSO detects gamma radiation where the gamma response can be subtracted from the total signal to improve SNR and contrast. The thickness of the LYSO scintillator is optimized such that it acts as light diffuser to spread the scintillation light generated in CsI: Tl over multiple SiPM pixels for accurate estimation of the beta(+) interaction location. The probe shows < 1 mm FWHM spatial resolution in the presence of large background radiation. The probe was used to study rabbits with tongue tumors. The experimental results show that the probe can successfully locate the tongue tumors in its active imaging area. C1 [Sabet, Hamid; Nagarkar, Vivek V.] RMD Inc, Watertown, MA 02472 USA. [Stack, Brendan C., Jr.] Univ Arkansas, Med Sci, Little Rock, AR 72205 USA. RP Sabet, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM HSabet@MGH.Harvard.edu FU U.S. National Institute of Health [1R43CA168100-01A1] FX This work was supported in part by the U.S. National Institute of Health under Grant 1R43CA168100-01A1. NR 28 TC 0 Z9 0 U1 1 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9499 EI 1558-1578 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD OCT PY 2015 VL 62 IS 5 BP 1927 EP 1934 DI 10.1109/TNS.2015.2446434 PN 1 PG 8 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA CU0XK UT WOS:000363242200001 ER PT J AU MacIsaac, RL Khatri, P Bendszus, M Bracard, S Broderick, J Campbell, B Ciccone, A Davalos, A Davis, SM Demchuk, A Diener, HC Dippel, D Donnan, GA Fiehler, J Fiorella, D Goyal, M Hacke, W Hill, MD Jahan, R Jauch, E Jovin, T Kidwell, CS Liebeskind, D Majoie, CB Martins, SCO Mitchell, P Mocco, J Muir, KW Nogueira, R Saver, JL Schonewille, WJ Siddiqui, AH Thomalla, G Tomsick, TA Turk, AS White, P Zaidat, O Lees, KR AF MacIsaac, Rachael L. Khatri, Pooja Bendszus, Martin Bracard, Serge Broderick, Joseph Campbell, Bruce Ciccone, Alfonso Davalos, Antoni Davis, Stephen M. Demchuk, Andrew Diener, Hans-Christoph Dippel, Diederik Donnan, Geoffrey A. Fiehler, Jens Fiorella, David Goyal, Mayank Hacke, Werner Hill, Michael D. Jahan, Reza Jauch, Edward Jovin, Tudor Kidwell, Chelsea S. Liebeskind, David Majoie, Charles B. Ouriques Martins, Sheila Cristina Mitchell, Peter Mocco, J. Muir, Keith W. Nogueira, Raul Saver, Jeffrey L. Schonewille, Wouter J. Siddiqui, Adnan H. Thomalla, Goetz Tomsick, Thomas A. Turk, Aquilla S. White, Philip Zaidat, Osama Lees, Kennedy R. CA VISTA Endovasc Collaboration TI A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: ThRombEctomy And tPA (TREAT) analysis: statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE acute; endovascular; ischemic stroke; meta-analysis; protocols; treatment ID CUMULATIVE METAANALYSIS; IMAGING SELECTION; CLINICAL-TRIALS; END-POINTS; REVASCULARIZATION; DEVICE; IMPLEMENTATION; THROMBOLYSIS; ALTEPLASE; SWIFT AB RationaleEndovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator. Aims and DesignThis statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group. Study OutcomesThis protocol will specify the primary outcome for efficacy, as favorable' outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasminogen activator alone on full scale modified Rankin Scale at 3 months?' and to what extent do key patient characteristics influence the treatment effect of endovascular therapy?'. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator-ineligible patients, should data allow. DiscussionThis collaborative meta-analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication. C1 [MacIsaac, Rachael L.; Lees, Kennedy R.; VISTA Endovasc Collaboration] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Khatri, Pooja; Broderick, Joseph; Tomsick, Thomas A.] Univ Cincinnati, Cincinnati, OH USA. [Bendszus, Martin] Univ Heidelberg Hosp, Heidelberg, Germany. [Bracard, Serge] CHRU Nancy, Nancy, France. [Campbell, Bruce] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Ciccone, Alfonso] Azienda Osped Carlo Poma Mantova, Dept Cardiothorac Vasc, Mantua, Italy. [Davalos, Antoni] Hosp Univ Germans Trias i Pujol, Dept Neurol, Barcelona, Spain. [Davis, Stephen M.] Royal Melbourne Hosp, Dept Neurol, Parkville, Vic 3050, Australia. [Demchuk, Andrew] Univ Calgary, Calgary, AB, Canada. [Diener, Hans-Christoph] Univ Hosp Essen, Dept Neurol, Essen, Germany. [Dippel, Diederik] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [Donnan, Geoffrey A.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia. [Fiehler, Jens] Univ Med Ctr Hamburg Eppendorf, Dept Neuroradiol, Hamburg, Germany. [Fiorella, David] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Goyal, Mayank] Hotchkiss Brain Inst, Calgary, AB, Canada. [Hacke, Werner] Heidelberg Univ, Dept Neurol, Heidelberg, Germany. [Hill, Michael D.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Jahan, Reza] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. [Jauch, Edward] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Jovin, Tudor] Univ Pittsburgh, Dept Neurol, UPMC, Stroke Inst, Pittsburgh, PA 15260 USA. [Kidwell, Chelsea S.] Univ Arizona, Dept Neurol, Tucson, AZ USA. [Kidwell, Chelsea S.] Univ Arizona, Dept Med Imaging, Tucson, AZ USA. [Liebeskind, David] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Majoie, Charles B.] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands. [Ouriques Martins, Sheila Cristina] Hosp Clin Porto Alegre, Dept Neurol, Porto Alegre, RS, Brazil. [Mitchell, Peter] Univ Melbourne, Melbourne Hlth, Melbourne, Vic, Australia. [Mitchell, Peter] Royal Melbourne Subject, Melbourne, Vic, Australia. [Mocco, J.] Mt Sinai Hosp, New York, NY 10029 USA. [Muir, Keith W.] Univ Glasgow, Inst Neurosci & Psychol, Ctr Stroke & Brain Imaging Res, Glasgow, Lanark, Scotland. [Muir, Keith W.] So Gen Hosp, Inst Neurol Sci, Glasgow G51 4TF, Lanark, Scotland. [Nogueira, Raul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Schonewille, Wouter J.] St Antonius Hosp, Dept Neurol, Utrecht, Netherlands. [Siddiqui, Adnan H.] SUNY Buffalo, Buffalo, NY 14260 USA. [Thomalla, Goetz] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Hamburg, Germany. [Turk, Aquilla S.] Med Univ S Carolina, Charleston, SC 29425 USA. [White, Philip] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Zaidat, Osama] Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP MacIsaac, RL (reprint author), Care of Fulton RL, Univ Glasgow, South Glasgow Univ Hosp, Inst Cardiovasc & Med Sci, Off Block,Room m0-07,Govan Rd, Glasgow G51 4TF, Lanark, Scotland. EM rachael.fulton@glasgow.ac.uk RI Muir, Keith/A-7670-2011 OI Muir, Keith/0000-0001-9535-022X FU Genentech; Penumbra; Biogen; DFG [SFB 936]; BMBF; Acandis; Bayer; Boehringer Ingelheim; Codman; Covidien; MicroVention; Philips; Sequent; Siemens; Stryker; BrainsGate; Pfizer; St. Jude Medical; AstraZeneca; GSK; Lundbeck; Novartis; Janssen-Cilag; Sanofi-Aventis; Syngis; Talecris; DFG; European Union; National Institutes of Health (NIH); Bertelsmann Foundation; Heinz-Nixdorf Foundation; Guerbet; Vascular Dynamics; Roche; French Ministry of Health; Boerhinger Ingelheim; Teva; BMS Pfizer; Allergan; Ever Neuropharma; AngioCare; Covidien/ev3; Medac/Lamepro; Codman/JnJ; Microvention/Terumo; Siemens Medical Imaging; Sequent Medical; ev3; Hoffman La Roche; Rapid Medical; Bayer Healthcare; Bristol-Myers-Squibb/Pfizer; NIH; Toshiba FX Dr MacIsaac: None. Dr Khatri received financial support to Department for research roles from Genentech (lead principal investigator [PI] of Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis [PRISMS] trial), Penumbra (neurology PI of Assess the Penumbra System in the Treatment of Acute Stroke [THERAPY] trial), and Biogen (Data and Safety Monitoring Board [DSMB] member). Dr Hacke is a steering committee member for Solitaire FR as Primary Treatment for Acute Ischemic Stroke (SWIFT-PRIME) and the Chair of Virtual International Stroke Trials Archive (VISTA)- Endovascular. Dr Fiehler received funding from DFG, SFB 936 Multisite Communication in the Brain and BMBF for Airchill Research Project. He received consultant/lecturer fees from Acandis, Bayer, Boehringer Ingelheim, Codman, Covidien, MicroVention, Penumbra, Philips, Sequent, Siemens, and Stryker. Dr Saver is an employee of the University of California (UC). UC Regents received funding for Dr Saver's services as a scientific consultant to Covidien, Stryker, BrainsGate, Pfizer, and St. Jude Medical. He is an unpaid site investigator in multicenter trials run by Lundbeck for which the UC Regents received payments for enrollment of subjects. He is also an unpaid consultant to Genentech for PRISMS trial. UC has patent rights in retrieval devices for stroke. Dr Diener received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from Abbott, Allergan, AstraZeneca, Bayer Vital, BMS, Boehringer Ingelheim, CoAxia, Corimmun, Covidien, Daiichi-Sankyo, D-Pharm, Fresenius, GlaxoSmithKline, Janssen-Cilag, Johnson & Johnson, Knoll, Lilly, MSD, Medtronic, MindFrame, Neurobiological Technologies, Novartis, Novo-Nordisk, Paion, Parke-Davis, Pfizer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, Syngis, Talecris, Thrombogenics, WebMD Global, Wyeth, and Yamanouchi. He received financial support for research projects from AstraZeneca, GSK, Boehringer Ingelheim, Lundbeck, Novartis, Janssen-Cilag, Sanofi-Aventis, Syngis and Talecris. The department received research grants from DFG, BMBF, European Union, National Institutes of Health (NIH), Bertelsmann Foundation and Heinz-Nixdorf Foundation.; He is also an editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerznews, and guidelines of the German Neurological Society; coeditor of Cephalalgia, editorial board of Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. Dr Bendszus is a PI of Comparison of Thrombectomy and Standard Care for Ischemic Stroke in Patients Ineligibility for Tissue Plasminogen Activator Treatment [THRILL; uncompensated) and received consultant/lecture fees from Codman, Guerbet, Novartis, Vascular Dynamics, and Roche. Dr Bracard received grant from French Ministry of Health for Trial and Cost Effectiveness Evaluation of Intra-Arterial Thrombectomy in Acute Ischemic Stroke (THRACE). Dr Broderick received research monies to department from Genentech (PRISMS SC); travel to conference payment from Boerhinger Ingelheim. Dr Ciccone received consultant/lecture fees from Boehringer Ingelheim and Teva. Dr Davalos received honoraria from Medtronic. Dr Davis is a consultant to Boehringer Ingelheim and received travel grants from BMS Pfizer, Allergan, Covidien, and Ever Neuropharma.; Dr Dippel received nominal unrestricted grants from AngioCare, Covidien/ev3, Medac/Lamepro, and Penumbra. Dr Fiorella royalties and consulting fees frome Codman/JnJ; consulting fees and research support from Penumbra; research support from Microvention/Terumo, Siemens Medical Imaging, and Sequent Medical; and consulting fees from ev3. Dr Goyal is a consultant to Covidien (educational engagements).; Dr Hill received research grant from Hoffman La Roche, and he is a consultant to Merck (adjudication committee for clinical trial). Dr Jauch received research grants from Genentech (Executive Committee PRISMS Trial). Dr Jovin is a consultant to Silk Road Medical and an unpaid consultant to Covidien Vascular, and Stryker Neurovascular. Dr Liebeskind is a consultant to Stryker and Covidien and an employee of UC, which holds a patent on retriever devices for stroke, at the time of this work. Dr Majoie received payment for lecture to institution from Stryker. Dr Mocco is a PI of THERAPY, Perfusion Imaging Selection of Ischemic Stroke Patients for Endovascular Therapy (POSITIVE), Large Aneurysm Randomized Trial: Flow Diversion Versus Traditional Endovascular Coiling Therapy (LARGE), Framing Eighteen Coils in Cerebral Aneurysms Trial (FEAT) Trial, and Barrel Study; he is a consultant to Medina Medical, Edge Therapeutics, Pulsar, and Lazarus Effect; he is a science advisory board member for Codman Neurovascular; and he is an investor of Blockade Medical and Medina Medical. Dr Muir is an advisory board memebr for Covidien in 2011. Dr Nogueira received support from Covidien (Study of Tamoxifen and Raloxifene [STAR] Trial Angiographic Core Laboratory - significant), Penumbra (3D Separator Trial Executive Committee - no payment), and Rapid Medical (Stroke Trial DSMB - modest). Dr Siddiqui received financial interests from Hotspur, Intratech Medical, StimSox, Valor Medical, Blockade Medical, Lazarus Effect, Pulsar Vascular, and Medina Medical. He is a consultant to Codman & Shurtleff, Covidien Vascular Therapies, GuidePoint Global Consulting, Penumbra, Stryker, Pulsar Vascular, Microvention, Lazarus Effect, Blockade Medical, and Reverse Medical. He is a National Steering Committee member of Penumbra, 3D Separator trial; Covidien, for SWIFT-PRIME trial; MicroVention, for Pivotal Study of the FRED [Flow Redirection Intraluminal Device] Stent System in the Treatment of Intracranial Aneurysms (FRED) trial. He is also a member of speakers' bureaus for Codman & Shurtleff and an advisory board member for Codman & Shurtleff, Covidien Neurovascular, ICAVL, and Medina Medical, and he received honoraria from Abbott Vascular, Codman & Shurtleff, and Penumbra. Dr Thomalla is a neurological principal investigator of THRILL and received consultant/lecture fees from Bayer Healthcare, Bristol-Myers-Squibb/Pfizer, Boehringer Ingelheim, and Covidien. Dr Tomsick is a coprincipal investigator of the NIH-funded Interventional Management of Stroke (IMS) III trial. Dr Turk received research grants from Toshiba. He is a consultant to Penumbra, Stryker, Lazarus Effect, and Siemens, and he is a member of the speakers' Bureau for Penumbra. Dr White is an educational consultant to Codman and Microvention, and he received research grant from Microvention for Stroke: An Evaluation of Thrombectomy in the Aging Brain (STABILISE) Trial and travel support from Microvention. Dr Zaidat is a consultant/speaker for Penumbra, Stryker, and Covidien. Dr Lees plays a leadership role in VISTA, a DMC member for REVASCAT, and a scientific committee member for SITS and SITS-OPEN. He is also the president of ESO that receives sponsorship from companies. NR 32 TC 6 Z9 6 U1 4 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD OCT PY 2015 VL 10 SU A100 SI SI BP 136 EP 144 DI 10.1111/ijs.12622 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CU6QW UT WOS:000363658700025 PM 26352438 ER PT J AU Kereiakes, DJ Yeh, RW Massaro, JM Driscoll-Shempp, P Cutlip, DE Steg, PG Gershlick, AH Darius, H Meredith, IT Ormiston, J Tanguay, JF Windecker, S Garratt, KN Kandzari, DE Lee, DP Simon, DI Iancu, AC Trebacz, J Mauri, L AF Kereiakes, Dean J. Yeh, Robert W. Massaro, Joseph M. Driscoll-Shempp, Priscilla Cutlip, Donald E. Steg, P. Gabriel Gershlick, Anthony H. Darius, Harald Meredith, Ian T. Ormiston, John Tanguay, Jean-Francois Windecker, Stephan Garratt, Kirk N. Kandzari, David E. Lee, David P. Simon, Daniel I. Iancu, Adrian Corneliu Trebacz, Jaroslaw Mauri, Laura CA DAPT Study Investigators TI Stent Thrombosis in Drug-Eluting or Bare-Metal Stents in Patients Receiving Dual Antiplatelet Therapy SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bare-metal stents; drug-eluting stents; dual antiplatelet therapy; stent thrombosis ID 5-YEAR CLINICAL-OUTCOMES; ST-SEGMENT ELEVATION; CORONARY STENTS; MYOCARDIAL-INFARCTION; AMERICAN-COLLEGE; RANDOMIZED-TRIAL; RESTENOSIS; GUIDELINES; EFFICACY; IMPACT AB OBJECTIVES This study sought to compare rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE) (composite of death, myocardial infarction, or stroke) after coronary stenting with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who participated in the DAPT (Dual Antiplatelet Therapy) study, an international multicenter randomized trial comparing 30 versus 12 months of dual antiplatelet therapy in subjects undergoing coronary stenting with either DES or BMS. BACKGROUND Despite antirestenotic efficacy of coronary DES compared with BMS, the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Many clinicians perceive BMS to be associated with fewer adverse ischemic events and to require shorter-duration dual antiplatelet therapy than DES. METHODS Prospective propensity-matched analysis of subjects enrolled into a randomized trial of dual antiplatelet therapy duration was performed. DES-and BMS-treated subjects were propensity-score matched in a many-to-one fashion. The study design was observational for all subjects 0 to 12 months following stenting. A subset of eligible subjects without major ischemic or bleeding events were randomized at 12 months to continued thienopyridine versus placebo; all subjects were followed through 33 months. RESULTS Among 10,026 propensity-matched subjects, DES-treated subjects (n = 8,308) had a lower rate of stent thrombosis through 33 months compared with BMS-treated subjects (n = 1,718, 1.7% vs. 2.6%; weighted risk difference -1.1%, p = 0.01) and a noninferior rate of MACCE (11.4% vs. 13.2%, respectively, weighted risk difference -1.8%, p = 0.053, noninferiority p < 0.001). CONCLUSIONS DES-treated subjects have long-term rates of stent thrombosis that are lower than BMS-treated subjects. (The Dual Antiplatelet Therapy Study [DAPT study]; NCT00977938) (C) 2015 by the American College of Cardiology Foundation. C1 [Kereiakes, Dean J.] Christ Hosp, Heart & Vasc Ctr, Cincinnati, OH 45219 USA. [Kereiakes, Dean J.] Lindner Ctr Res & Educ, Cincinnati, OH USA. [Yeh, Robert W.; Massaro, Joseph M.; Driscoll-Shempp, Priscilla; Cutlip, Donald E.; Mauri, Laura] Harvard Clin Res Inst, Boston, MA USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiol, Boston, MA 02215 USA. [Steg, P. Gabriel] Univ Paris Diderot, Paris, France. [Steg, P. Gabriel] INSERM, U1148, Paris, France. [Steg, P. Gabriel] Hop Bichat Claude Bernard, Dept Hosp Univ FIRE, AP HP, F-75877 Paris, France. [Steg, P. Gabriel] Univ London Imperial Coll Sci Technol & Med, NHLI, Royal Brompton Hosp, London, England. [Gershlick, Anthony H.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Gershlick, Anthony H.] Univ Hosp Leicester, Natl Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Darius, Harald] Vivantes Neukoelln Med Ctr, Dept Cardiol Angiol Nephrol & Intens Care Med, Berlin, Germany. [Meredith, Ian T.] Monash Univ, Monash Hlth, Monash Heart, Clayton, Vic 3800, Australia. [Ormiston, John] Mercy Hosp, Auckland, New Zealand. [Tanguay, Jean-Francois] Univ Montreal, Dept Med, Montreal Heart Inst, Div Intervent Cardiol, Montreal, PQ H3C 3J7, Canada. [Windecker, Stephan] Univ Hosp Bern, Dept Cardiol, CH-3010 Bern, Switzerland. [Garratt, Kirk N.] Christiana Care, Ctr Heart & Vasc Hlth, Wilmington, DE USA. [Kandzari, David E.] Piedmont Heart Inst, Atlanta, GA USA. [Lee, David P.] Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Simon, Daniel I.] Univ Hosp Case Med Ctr, Harrington Heart & Vasc Inst, Cleveland, OH USA. [Iancu, Adrian Corneliu] Univ Med Iuliu Hatieganu, Heart Inst, Cluj Napoca, Romania. [Trebacz, Jaroslaw] Jan Pawel II Hosp Krakow, Krakow, Poland. [Mauri, Laura] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Mauri, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM lmauri1@partners.org FU NIH; Gilead Sciences; Medtronic Inc. FX JACC: Cardiovascular Interventions CME Editor Olivia Hung, MD, PhD, has received research grant support from NIH T32, Gilead Sciences and Medtronic Inc. NR 28 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 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD OCT PY 2015 VL 8 IS 12 BP 1552 EP 1562 DI 10.1016/j.jcin.2015.05.026 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU1GN UT WOS:000363268600010 PM 26493248 ER PT J AU Rosenberg, SM Partridge, AH AF Rosenberg, Shoshana M. Partridge, Ann H. TI New Insights Into Nonadherence With Adjuvant Endocrine Therapy Among Young Women With Breast Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CLINICAL-PRACTICE; HORMONAL-THERAPY; AMERICAN SOCIETY; CHEMOTHERAPY; ADHERENCE; UPDATE C1 [Rosenberg, Shoshana M.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ann_partridge@dfci.harvard.edu NR 14 TC 0 Z9 0 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD OCT PY 2015 VL 107 IS 10 AR djv245 DI 10.1093/jnci/djv245 PG 2 WC Oncology SC Oncology GA CU0KK UT WOS:000363204900027 ER PT J AU Sperandio, FF Simoes, A Correa, L Aranha, ACC Giudice, FS Hamblin, MR Sousa, SCOM AF Sperandio, Felipe F. Simoes, Alyne Correa, Luciana Aranha, Ana Cecilia C. Giudice, Fernanda S. Hamblin, Michael R. Sousa, Suzana C. O. M. TI Low-level laser irradiation promotes the proliferation and maturation of keratinocytes during epithelial wound repair SO JOURNAL OF BIOPHOTONICS LA English DT Article DE low-level laser therapy; wound healing; keratins; p63 protein; Cyclin D1; photobiomodulation; HaCaT keratinocytes ID IN-VITRO; STEM-CELLS; THERAPY; SKIN; DIFFERENTIATION; PHOTOTHERAPY; FIBROBLASTS; EXPRESSION; CANCER; SCARS AB Low-level laser therapy (LLLT) has been extensively employed to improve epithelial wound healing, though the exact response of epithelium maturation and stratification after LLLT is unknown. Thus, this study aimed to assess the in vitro growth and differentiation of keratinocytes (KCs) and in vivo wound healing response when treated with LLLT. Human KCs (HaCaT cells) showed an enhanced proliferation with all the employed laser energy densities (3, 6 and 12J/cm(2), 660nm, 100mW), together with an increased expression of Cyclin D1. Moreover, the immunoexpression of proteins related to epithelial proliferation and maturation (p63, CK10, CK14) all indicated a faster maturation of the migrating KCs in the LLLT-treated wounds. In that way, an improved epithelial healing was promoted by LLLT with the employed parameters; this improvement was confirmed by changes in the expression of several proteins related to epithelial proliferation and maturation. C1 [Sperandio, Felipe F.] Univ Fed Alfenas, Inst Biomed Sci, Dept Pathol & Parasitol, BR-37130000 Alfenas, MG, Brazil. [Sperandio, Felipe F.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sperandio, Felipe F.; Hamblin, Michael R.] Harvard Univ, Dept Dermatol, Sch Med, Boston, MA 02115 USA. [Simoes, Alyne] Univ Sao Paulo, Sch Dent, Dept Biomat & Oral Biol, BR-05508000 Sao Paulo, SP, Brazil. [Correa, Luciana; Sousa, Suzana C. O. M.] Univ Sao Paulo, Sch Dent, Dept Oral Pathol, BR-05508000 Sao Paulo, SP, Brazil. [Aranha, Ana Cecilia C.] Univ Sao Paulo, Sch Dent, Dept Restorat Dent, Special Lab Lasers Dent LELO, BR-05508000 Sao Paulo, SP, Brazil. [Giudice, Fernanda S.] Natl Inst Oncogenom, AC Camargo Canc Ctr, BR-01508010 Sao Paulo, SP, Brazil. [Giudice, Fernanda S.] Natl Inst Translat Neurosci, BR-01508010 Sao Paulo, SP, Brazil. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Sperandio, FF (reprint author), Univ Fed Alfenas, Inst Biomed Sci, Dept Pathol & Parasitol, BR-37130000 Alfenas, MG, Brazil. EM sperandio@usp.br RI Sousa, Suzana/H-6154-2012; Correa, Luciana/H-3875-2012 FU CAPES; FAPESP; US NIH [R01AI050875] FX The authors wish to thank CAPES and FAPESP for the grants received; MRH was supported by US NIH grant R01AI050875. NR 52 TC 9 Z9 9 U1 1 U2 7 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1864-063X EI 1864-0648 J9 J BIOPHOTONICS JI J. Biophotonics PD OCT PY 2015 VL 8 IS 10 BP 795 EP 803 DI 10.1002/jbio.201400064 PG 9 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA CU4ES UT WOS:000363480400003 PM 25411997 ER PT J AU Chan, JJ Cupples, LA Kiel, DP O'Donnell, CJ Hoffmann, U Samelson, EJ AF Chan, Jimmy J. Cupples, L. Adrienne Kiel, Douglas P. O'Donnell, Christopher J. Hoffmann, Udo Samelson, Elizabeth J. TI QCT Volumetric Bone Mineral Density and Vascular and Valvular Calcification: The Framingham Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BONE; AGING; QCT; OSTEOPOROSIS; VASCULAR CALCIFICATION; VALVULAR CALCIFICATION; EPIDEMIOLOGY ID CORONARY-ARTERY CALCIUM; ABDOMINAL AORTIC CALCIFICATION; CARDIOVASCULAR-DISEASE; VALVE CALCIFICATION; COMPUTED-TOMOGRAPHY; TRABECULAR BONE; DEFICIENT MICE; RISK-FACTORS; GLA PROTEIN; LONG-TERM AB There is increasing evidence that bone and vascular calcification share common pathogenesis. Little is known about potential links between bone and valvular calcification. The purpose of this study was to determine the association between spine bone mineral density (BMD) and vascular and valvular calcification. Participants included 1317 participants (689 women, 628 men) in the Framingham Offspring Study (mean age 60 years). Integral, trabecular, and cortical volumetric bone density (vBMD) and arterial and valvular calcification were measured from computed tomography (CT) scans and categorized by sex-specific quartiles (Q4 = high vBMD). Calcification of the coronary arteries (CAC), abdominal aorta (AAC), aortic valve (AVC), and mitral valve (MVC) were quantified using the Agatston Score (AS). Prevalence of any calcium (AS > 0) was 69% for CAC, 81% for AAC, 39% for AVC, and 20% for MVC. In women, CAC increased with decreasing quartile of trabecular vBMD: adjusted mean CAC = 2.1 (Q4), 2.2 (Q3), 2.5 (Q2), 2.6 (Q1); trend p = 0.04. However, there was no inverse trend between CAC and trabecular vBMD in men: CAC = 4.3 (Q4), 4.3 (Q3), 4.2 (Q2), 4.3 (Q1); trend p = 0.92. AAC increased with decreasing quartile of trabecular vBMD in both women (AAC = 4.5 [Q4], 4.8 [Q3], 5.4 [Q2], 5.1 [Q1]; trend p = 0.01) and men (AAC = 5.5 [Q4], 5.8 [Q3], 5.9 [Q2], 6.2 [Q1]; trend p = 0.01). We observed no association between trabecular vBMD and AVC or MVC in women or men. Finally, cortical vBMD was unrelated to vascular calcification and valvular calcification in women and men. Women and men with low spine vBMD have greater severity of vascular calcification, particularly at the abdominal aorta. The inverse relation between AAC and spine vBMD in women and men may be attributable to shared etiology and may be an important link on which to focus treatment efforts that can target individuals at high risk of both fracture and cardiovascular events. (C) 2015 American Society for Bone and Mineral Research. C1 [Chan, Jimmy J.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Kiel, Douglas P.; O'Donnell, Christopher J.; Hoffmann, Udo; Samelson, Elizabeth J.] Harvard Univ, Sch Med, Boston, MA USA. [Kiel, Douglas P.; Samelson, Elizabeth J.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Kiel, Douglas P.; Samelson, Elizabeth J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [O'Donnell, Christopher J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Samelson, EJ (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM samelson@hsl.harvard.edu OI Kiel, Douglas/0000-0001-8474-0310 FU National Institutes of Health [K01 AR053118]; Medical Student Training in Aging Research Grants [1T35AG038027-03, R01 AR053986, R01 AR41398]; National Heart, Lung, and Blood Institute [N01-HC-25195] FX This work was supported by National Institutes of Health Grant K01 AR053118; Medical Student Training in Aging Research Grants 1T35AG038027-03, R01 AR053986, and R01 AR41398; and National Heart, Lung, and Blood Institute's Framingham Heart Study Grant N01-HC-25195. NR 59 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2015 VL 30 IS 10 BP 1767 EP 1774 DI 10.1002/jbmr.2530 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU1MR UT WOS:000363286500004 PM 25871790 ER PT J AU Lee, S Mannstadt, M Guo, J Kim, SM Yi, HS Khatri, A Dean, T Okazaki, M Gardella, TJ Juppner, H AF Lee, Sihoon Mannstadt, Michael Guo, Jun Kim, Seul Min Yi, Hyon-Seung Khatri, Ashok Dean, Thomas Okazaki, Makoto Gardella, Thomas J. Jueppner, Harald TI A Homozygous [Cys25]PTH(1-84) Mutation That Impairs PTH/PTHrP Receptor Activation Defines a Novel Form of Hypoparathyroidism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE IDIOPATHIC HYPOPARATHYROIDISM; PSEUDOHYPOPARATHYROIDISM TYPE IB; PTH(1-84) MUTATION ID PSEUDOHYPOPARATHYROIDISM TYPE-IB; FAMILIAL ISOLATED HYPOPARATHYROIDISM; AUTOSOMAL-DOMINANT HYPOPARATHYROIDISM; ALBRIGHTS HEREDITARY OSTEODYSTROPHY; PARATHYROID-HORMONE RESISTANCE; IMPRINTING CONTROL ELEMENT; DNA-BINDING DOMAIN; GNAS LOCUS; IMMUNORADIOMETRIC ASSAY; EPIGENETIC DEFECTS AB Hypocalcemia and hyperphosphatemia are encountered in idiopathic hypoparathyroidism (IHP) and pseudohypoparathyroidism type Ib (PHP1B). In contrast to PHP1B, which is caused by resistance toward parathyroid hormone (PTH), the genetic defects leading to IHP impair production of this important regulator of mineral ion homeostasis. So far, only five PTH mutations were shown to cause IHP, each of which is located in the hormone's pre-pro leader segment and thus impair hormone secretion. In three siblings affected by IHP, we now identified a homozygous arginine-to-cysteine mutation at position 25 (R25C) of the mature PTH(1-84) polypeptide; heterozygous family members are healthy. Depending on the assay used for evaluating these patients, plasma PTH levels were either low or profoundly elevated, thus leading to ambiguities regarding the underlying diagnosis, namely IHP or PHP1B. Consistent with increased PTH levels, recombinant [Cys25]PTH(1-84) and wild-type PTH(1-84) were secreted equally well by transfected COS-7 cells. However, synthetic [Cys25]PTH(1-34) was found to have a lower binding affinity for the PTH receptor type-1 (PTH1R) than PTH(1-34) and consequently a lower efficiency for stimulating cAMP formation in cells expressing this receptor. Consistent with these in vitro findings, long-term infusion of [Cys25]PTH(1-34) resulted only in minimal calcemic and phosphaturic responses, despite readily detectable levels of [Cys25]PTH(1-34) in plasma. The mineral ion abnormalities observed in the three IHP patients are thus most likely caused by the inherited homozygous missense PTH mutation, which reduces bioactivity of the secreted hormone. Based on these findings, screening for PTH(1-84) mutations should be considered when clinical and laboratory findings are consistent with PHP1B, but GNAS methylation changes have been excluded. Differentiating between IHP and PHP1B has considerable implications for genetic counseling, therapy, and long-term outcome because treatment of IHP patients with inappropriately high doses of active vitamin D and calcium can contribute to development of nephrocalcinosis and chronic kidney disease. (C) 2015 American Society for Bone and Mineral Research. C1 [Lee, Sihoon; Kim, Seul Min; Yi, Hyon-Seung] Gachon Univ, Sch Med, Dept Internal Med, Inchon, South Korea. [Lee, Sihoon; Kim, Seul Min; Yi, Hyon-Seung] Gachon Univ, Sch Med, Mol Endocrinol Lab, Inchon, South Korea. [Mannstadt, Michael; Guo, Jun; Khatri, Ashok; Dean, Thomas; Okazaki, Makoto; Gardella, Thomas J.; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Mannstadt, Michael; Guo, Jun; Khatri, Ashok; Dean, Thomas; Okazaki, Makoto; Gardella, Thomas J.; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 10,50 Blossom St, Boston, MA 02114 USA. EM hjueppner@partners.org FU National Research Foundation of Korea [NRF-2013R1A1A1A05005629]; National Institute of Diabetes and Digestive and Kidney Disease [R01-DK46718, P01-DK11794, R01-DK100584] FX The authors thank all family members for their participation and Professors Jaesang Kim, John Lew, Ung-il Chung, Sung-Kil Lim, Jean-Pierre Vilardaga, and Henry Kronenberg for their insightful advice. Supported by the Basic Science Research Program, National Research Foundation of Korea (NRF-2013R1A1A1A05005629 to SL) and by grants from the National Institute of Diabetes and Digestive and Kidney Disease (R01-DK46718 to HJ; P01-DK11794, project I to TJG and project IV to HJ; and R01-DK100584 to MM). NR 66 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2015 VL 30 IS 10 BP 1803 EP 1813 DI 10.1002/jbmr.2532 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU1MR UT WOS:000363286500009 PM 25891861 ER PT J AU Trombetta-eSilva, J Rosset, EA Hepfer, RG Wright, GJ Baicu, C Yao, H Bradshaw, AD AF Trombetta-eSilva, Jessica Rosset, Emilie A. Hepfer, R. Glenn Wright, Gregory J. Baicu, Catalin Yao, Hai Bradshaw, Amy D. TI Decreased Mechanical Strength and Collagen Content in SPARC-Null Periodontal Ligament Is Reversed by Inhibition of Transglutaminase Activity SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BONE MATRIX; NONCOLLAGENOUS PROTEINS; DENTAL BIOLOGY; EXTRACELLULAR MATRIX; CROSS-LINKS ID SMOOTH-MUSCLE-CELLS; CROSS-LINKING; TISSUE TRANSGLUTAMINASE; EXTRACELLULAR-MATRIX; DEFICIENT MICE; FACTOR XIIIA; I COLLAGEN; FIBRONECTIN; OSTEONECTIN; SEROTONIN AB The periodontal ligament (PDL) is a critical tissue that provides a physical link between the mineralized outer layer of the tooth and the alveolar bone. The PDL is composed primarily of nonmineralized fibrillar collagens. Expression of secreted protein acidic and rich in cysteine (SPARC/osteonectin), a collagen-binding matricellular protein, has been shown to be essential for collagen homeostasis in PDL. In the absence of SPARC, PDL collagen fibers are smaller and less dense than fibers that constitute WT PDL. The aim of this study was to identify cellular mechanisms by which SPARC affected collagen fiber assembly and morphology in PDL. Cross-linking of fibrillar collagens is one parameter that is known to affect insoluble collagen incorporation and fiber morphology. Herein, the reduction in collagen fiber size and quantity in the absence of SPARC expression was shown to result in a PDL with reduced molar extraction force in comparison to that of WT mice (C57Bl/6J). Furthermore, an increase in transglutaminase activity was found in SPARC-null PDL by biochemical analyses that was supported by immunohistochemical results. Specifically, collagen I was identified as a substrate for transglutaminase in PDL and transglutaminase activity on collagen I was found to be greater in SPARC-null tissues in comparison to WT. Strikingly, inhibition of transglutaminase activity in SPARC-null PDL resulted in increases in both collagen fiber thickness and in collagen content, whereas transglutaminase inhibitors injected into WT mice resulted in increases in collagen fiber thickness only. Furthermore, PDL treated with transglutaminase inhibitors exhibited increases in molar extraction force in WT and in SPARC-null mice. Thus, SPARC is proposed to act as a critical regulator of transglutaminase activity on collagen I with implications for mechanical strength of tissues. (C) 2015 American Society for Bone and Mineral Research. C1 [Trombetta-eSilva, Jessica; Rosset, Emilie A.; Yao, Hai; Bradshaw, Amy D.] Med Univ S Carolina, Dept Craniofacial Biol, Charleston, SC 29425 USA. [Hepfer, R. Glenn; Wright, Gregory J.; Yao, Hai] Clemson Univ, Dept Bioengn, Clemson, SC USA. [Baicu, Catalin; Bradshaw, Amy D.] Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. [Bradshaw, Amy D.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Bradshaw, AD (reprint author), Med Univ S Carolina, 114 Doughty St,MSC 773, Charleston, SC 29425 USA. EM bradshad@musc.edu FU NIH [F30DE023009-01, F31DE023482, R01DE021134]; Veteran's Administration [1I01BX001385-01A1] FX This work was supported by NIH F30DE023009-01 (J.T-eS.), NIH predoctoral fellowship award F31DE023482 (GJW), Veteran's Administration Merit Award 1I01BX001385-01A1 (ADB), and NIH R01DE021134 (HY). NR 38 TC 3 Z9 3 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2015 VL 30 IS 10 BP 1914 EP 1924 DI 10.1002/jbmr.2522 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU1MR UT WOS:000363286500020 PM 25827352 ER PT J AU Roka, A Heist, EK Refaat, M Ruskin, J Mansour, M AF Roka, Attila Heist, E. Kevin Refaat, Marwan Ruskin, Jeremy Mansour, Moussa TI Novel Technique to Prevent Phrenic Nerve Injury During Pulmonary Vein Isolation Using Preprocedural Imaging SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; electroanatomical mapping; phrenic nerve; pulmonary vein isolation; radiofrequency ablation ID ATRIAL-FIBRILLATION; CRYOBALLOON ABLATION; CATHETER ABLATION; ANGIOGRAPHY; ANATOMY; TRIAL AB Prevention of Phrenic Injury Using Imaging IntroductionPhrenic nerve (PN) injury is one of the major complications of pulmonary vein isolation (PVI). Pace mapping for PN capture is routinely used to identify areas with high risk for injury along the anterior border of the right pulmonary veins (PVs). Our aim was to evaluate the feasibility of using preprocedural imaging to identify areas where no PN capture is possible along the anterior border of the right PVs, thus avoiding the need for pace mapping during PVI. Methods and ResultsIt was hypothesized that PN capture along the anterior border of the right PVs does not occur in the area where the right and left atria overlap. Three-dimensional segmentation of both atria was performed on preprocedural magnetic resonance and computed tomography angiograms in 40 patients before undergoing PVI. The area of overlap between the right and left atria was delineated. Image registration was performed during the procedure. Using pacing, regions with and without PN capture were marked along the anterior border of the right PVs. A total of 361 points were tested for PN stimulation (9 4 points/patient). PN capture occurred in 97 out of the 189 points (51%) in the area with no overlap between the right and left atria. No PN capture occurred in the area of overlap (172 points, P< 0.001). ConclusionDelineation of the area of overlap between the right and left atria derived from preprocedural imaging reliably identifies regions where PN pace capture does not occur. Testing for PN stimulation before ablation may not be necessary in these regions. C1 [Roka, Attila; Heist, E. Kevin; Refaat, Marwan; Ruskin, Jeremy; Mansour, Moussa] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Ctr Heart, 55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org FU Deane Institute for Integrative Research in Atrial Fibrillation and Stroke at Massachusetts General Hospital (Boston, MA); St. Jude Medical; Biosense Webster FX This work was supported by the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke at Massachusetts General Hospital (Boston, MA).; E. Kevin Heist reports research grants from St. Jude Medical, and serving as a consultant to Biosense Webster and St. Jude Medical. Jeremy Ruskin reports Fellowship support from St. Jude Medical, and serving as a consultant to Biosense Webster. Moussa Mansour reports research grants from Biosense Webster and St. Jude Medical, and serving as a consultant to Biosense Webster and St. Jude Medical. Other authors: No disclosures. NR 15 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2015 VL 26 IS 10 BP 1057 EP 1062 DI 10.1111/jce.12758 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU0MR UT WOS:000363211600009 PM 26183238 ER PT J AU Ozaydin, M Moazzami, K Kalantarian, S Lee, H Mansour, M Ruskin, JN AF Ozaydin, Mehmet Moazzami, Kasra Kalantarian, Shadi Lee, Hang Mansour, Moussa Ruskin, Jeremy N. TI Long-Term Outcome of Patients With Idiopathic Ventricular Fibrillation: A Meta-Analysis SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE arrhythmia; fibrillation; mortality; ventricles ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; EARLY REPOLARIZATION SYNDROME; HOSPITAL CARDIAC-ARREST; LIFE-THREATENING ARRHYTHMIAS; ANTIARRHYTHMIC-DRUG THERAPY; SHORT QT SYNDROME; BRUGADA-SYNDROME; FOLLOW-UP; J-WAVE; HEART-DISEASE AB Outcome of Idiopathic Ventricular Fibrillation BackgroundThe long-term outcome of the patients with idiopathic ventricular fibrillation (IVF) is not well known. Methods and ResultsRelevant studies published through May 21, 2014 were searched and identified in the MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE databases and a hand search of article references was also performed. Random-effect models were used for pooling proportions of mortality and recurrent events. Twenty-three studies were included with a total of 639 patients (449 males) with a mean age ranging from 33 to 51 years. Eighty percent of patients had received ICD implantation. Over an average of 5.3 years follow-up, 167 patients (31%) experienced a recurrence of ventricular arrhythmic events (proportion, 0.29 [95% CI 0.21-0.38]). Moreover, 17 patients (3.1%) died among all studies (proportion, 0.01 [95% CI 0.00-0.04]). No association was found between the induction of sustained ventricular tachycardia or ventricular fibrillation at baseline electrophysiological study and risk of recurrent ventricular arrhythmias (risk difference: 0.12 [95% CI, 0.08-0.32]). ConclusionsIn patients with IVF, this meta-analysis revealed an estimated recurrent event rate of 31% and a pooled mortality rate of 3.1% during an average of 5 years follow-up. The results of baseline electrophysiological studies are not predictive of future ventricular arrhythmias. C1 [Ozaydin, Mehmet; Moazzami, Kasra; Kalantarian, Shadi; Mansour, Moussa; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ozaydin, Mehmet] Suleyman Demirel Univ, Dept Cardiol, Fac Med, TR-32200 Isparta, Turkey. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Ruskin, JN (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM jruskin@partners.org FU Turkish Scientific and Technical Research Council (TUBITAK); Massachusetts General Hospital; St. Jude Medical; Biosense Webster; Boston Scientific; Biotronik; Advanced Medical Education; CardioInsight; Medtronic FX This study was supported by the Turkish Scientific and Technical Research Council (TUBITAK) Post-doctoral Research Fellowship Award (MO) and the Al Sagri Research Fund at Massachusetts General Hospital.; Dr. Mansour reports participation on research grants supported by St. Jude Medical, Biosense Webster, and Boston Scientific; he serves as consultant/advisory board member and has equity in NewPace Ltd. Dr. Ruskin reports the following: Fellowship grants: Biosense Webster, Biotronik, Boston Scientific; Scientific advisory board consulting fees: Advanced Medical Education, CardioInsight, Medtronic; Scientific advisory board equity interest: Element Science, InfoBionic, NewPace; Data monitoring committee: Gilead Sciences. Other authors: No disclosures. NR 51 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2015 VL 26 IS 10 BP 1095 EP 1104 DI 10.1111/jce.12737 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU0MR UT WOS:000363211600015 PM 26086294 ER PT J AU Cohn, BG Keim, SM Watkins, JW Camargo, CA AF Cohn, Brian G. Keim, Samuel M. Watkins, Joseph W. Camargo, Carlos A. TI DOES MANAGEMENT OF DIABETIC KETOACIDOSIS WITH SUBCUTANEOUS RAPID-ACTING INSULIN REDUCE THE NEED FOR INTENSIVE CARE UNIT ADMISSION? SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE diabetic ketoacidosis; DKA; insulin; intensive care; hospitalization ID INTRAVENOUS REGULAR INSULIN; ADULT PATIENTS; LISPRO; THERAPY; ASPART; ANALOG AB Background: In the last 20 years, rapidacting insulin analogs have emerged on the market, including aspart and lispro, which may be efficacious in the management of diabetic ketoacidosis (DKA) when administered by non-intravenous (i.v.) routes. Clinical Question: In patients with mild-to-moderate DKA without another reason for intensive care unit (ICU) admission, is the administration of a subcutaneous (s.c.) rapid-acting insulin analog a safe and effective alternative to a continuous infusion of i.v. regular insulin, and would such a strategy eliminate the need for ICU admission? Evidence Review: Five randomized controlled trials were identified and critically appraised. Results: The outcomes suggest that there is no difference in the duration of therapy required to resolve DKA with either strategy. Conclusion: Current evidence supports DKA management with s.c. rapid-acting insulin analogs in a non-ICU setting in carefully selected patients. (C) 2015 Elsevier Inc. C1 [Cohn, Brian G.; Watkins, Joseph W.] Washington Univ, Sch Med, Div Emergency Med, St Louis, MO USA. [Keim, Samuel M.] Univ Arizona, Dept Emergency Med, Coll Med, Tucson, AZ 85724 USA. [Camargo, Carlos A.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Camargo, Carlos A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Keim, SM (reprint author), Univ Arizona, Dept Emergency Med, Coll Med, POB 245057, Tucson, AZ 85724 USA. OI Camargo, Carlos/0000-0002-5071-7654 NR 23 TC 1 Z9 1 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2015 VL 49 IS 4 BP 530 EP 538 DI 10.1016/j.jemermed.2015.05.016 PG 9 WC Emergency Medicine SC Emergency Medicine GA CU0LF UT WOS:000363207200035 PM 26238182 ER PT J AU Neuhaus, V Bot, AG Guitton, TG Ring, DC AF Neuhaus, V. Bot, A. G. Guitton, T. G. Ring, D. C. TI Influence of surgeon, patient and radiographic factors on distal radius fracture treatment SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Article DE Distal radius fracture; interobserver agreement; operative treatment; patient characteristics; surgeon characteristics ID UNITED-STATES; INTEROBSERVER RELIABILITY; NONOPERATIVE TREATMENT; COLLES FRACTURE; CLASSIFICATION; DISPLACEMENT; PREDICTION; TRENDS; OLDER; AGE AB The purpose of this study was to evaluate surgeon, patient, and radiographic factors influencing the recommendation for operative treatment in distal radius fractures. In a web-based study 252 orthopaedic surgeons from a variety of countries reviewed 30 consecutive sets of radiographs of patients that presented to our emergency department with a fracture of the distal radius. Surgeons were randomly assigned to receive either 'Radiographs only' or 'Radiographs and clinical information'. Surgery was recommended on average 52% of the time whether or not surgeons received clinical information. Female surgeons, surgeons with less than 21 years of experience, and hand surgeons were more likely to recommend operative treatment, but these factors explained only 1% of the variation. Radiographic criteria (intra-articular fractures, ulnar styloid fractures, dorsal comminution, dorsal tilt, and ulnar variance) explained 49% of the variation. The overall agreement on treatment was moderate and slightly higher among surgeons that received radiographs alone. C1 [Neuhaus, V.; Bot, A. G.; Guitton, T. G.; Ring, D. C.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Neuhaus, V.] Univ Zurich Hosp, Div Trauma Surg, CH-8091 Zurich, Switzerland. RP Ring, DC (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Guitton, Thierry/0000-0002-2599-1985 FU 'Gottfried und Julia Bangerter-Rhyner-Stiftung', Switzerland FX VN was supported by the 'Gottfried und Julia Bangerter-Rhyner-Stiftung', Switzerland, for Scientific Research. AB reports grants from Prins Bernhard Cultuurfonds/Banning-de Jong Fonds, VSB fonds, Anna Fonds (outside the submitted work), grants from Anna Fonds, Penders Voetzorg, Chipsoft, DePuy Synthes, Reumafonds, Janssen-Cilag, Academisch Medisch Centrum, outside the submitted work to support printing his PhD thesis. NR 27 TC 1 Z9 2 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-1934 EI 2043-6289 J9 J HAND SURG-EUR VOL JI J. Hand Surg.-Eur. Vol. PD OCT PY 2015 VL 40 IS 8 BP 796 EP 804 DI 10.1177/1753193414555284 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CU3ZD UT WOS:000363464400005 PM 25342650 ER PT J AU Jones, CR Khandhar, SJ Ramratnam, M Mulukutla, SR Marroquin, OC Althouse, AD Rao, A Kato, K Jang, IK Toma, C AF Jones, Christopher R. Khandhar, Sameer J. Ramratnam, Mohun Mulukutla, Suresh R. Marroquin, Oscar C. Althouse, Andrew D. Rao, Anjali Kato, Koji Jang, Ik-Kyung Toma, Catalin TI Identification of Intrastent Pathology Associated With Late Stent Thrombosis Using Optical Coherence Tomography SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID DRUG-ELUTING STENTS; ELEVATION MYOCARDIAL-INFARCTION; LARGE 2-INSTITUTIONAL COHORT; ROUTINE CLINICAL-PRACTICE; HIGH-RISK PATIENTS; BARE-METAL STENTS; INTRAVASCULAR ULTRASOUND; TIME-COURSE; NEOATHEROSCLEROSIS; IMPLANTATION AB ObjectiveTo better characterize intrastent pathology using optical coherence tomography (OCT) in patients presenting with late and very late stent thrombosis (LST/VLST). BackgroundThe contribution of specific intrastent pathologies to the development of LST/VLST is not well understood. MethodsIn this single-center, retrospective, observational study of 796 consecutive patients treated for ST-segment elevation myocardial infarction (STEMI) with primary PCI we identified 57 patients (7.2%) in whom STEMI resulted from LST/VLST. Of the patients with LST/VLST, 21 patients (37%) had OCT performed at the discretion of the operator during PCI for LST/VLST. Independent reviewers performed qualitative offline analysis of OCT images to determine the cause of stent thrombosis defined as the specific intrastent pathology associated with thrombus deposition. ResultsThe principal intrastent pathology causing LST/VLST was determined to be stent malapposition in 11 patients (55%), of which 5 (25% of all LST/VLST patents) had findings suggestive of positive vessel remodeling. Neoatherosclerosis was determined to be the cause of LST/VLST in 7 patients (35%). LST/VLST resulted from uncovered stent struts in 2 patients (10%). Among all LST/VLST patients, in-hospital mortality (12.3%) and post-hospital target vessel failure (TVF) or cardiac death (21.7%, median follow-up 1.6 years) remained high. There was a trend towards decreased TVF or cardiac death (7.7% vs. 27.3% P=0.24) in patients who underwent OCT-guided therapy. ConclusionsLST/VLST remains a significant cause of STEMI and is associated with considerable morbidity and mortality. OCT use at the time of PCI consistently identifies significant intrastent pathology with potentially meaningful clinical impact. (J Interven Cardiol 2015;28:439-448) C1 [Jones, Christopher R.; Khandhar, Sameer J.; Ramratnam, Mohun; Mulukutla, Suresh R.; Marroquin, Oscar C.; Althouse, Andrew D.; Rao, Anjali; Toma, Catalin] Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA 15123 USA. [Kato, Koji; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Toma, C (reprint author), Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, 200 Lothrop St,A333, Pittsburgh, PA 15123 USA. EM tomacx@upmc.edu NR 40 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0896-4327 EI 1540-8183 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD OCT PY 2015 VL 28 IS 5 BP 439 EP 448 DI 10.1111/joic.12220 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU3UC UT WOS:000363449900005 PM 26381509 ER PT J AU Kim, SY Dodson, TB Do, DT Wadhwa, G Chuang, SK AF Kim, Sang Y. Dodson, Thomas B. Do, Duy T. Wadhwa, Gary Chuang, Sung-Kiang TI Factors Associated With Crestal Bone Loss Following Dental Implant Placement in a Longitudinal Follow-up Study SO JOURNAL OF ORAL IMPLANTOLOGY LA English DT Article DE crestal bone changes; dental implants; risk factors ID SPONTANEOUS EARLY EXPOSURE; FAILURE-TIME OBSERVATIONS; CONTROLLED CLINICAL-TRIAL; FRESH EXTRACTION SOCKETS; RADIOGRAPHIC EVALUATION; SUBMERGED IMPLANTS; TITANIUM IMPLANTS; LEVEL CHANGES; RISK-FACTORS; IMMEDIATE AB The purpose of this study is to estimate the magnitude of crestal bone loss and to identify factors associated with changes in crestal bone height following placement of dental implants. This was a retrospective cohort study, consisting of a sample derived from the population of patients who had at least 1 dental implant placed in a community practice over a 10-year period. A total of 11 predictor variables were grouped into demographic, related health status, anatomic, implant-specific, and operative categories. The primary outcome variable was a change in crestal bone height (mm) over the course of follow-up. The secondary outcome variable was crestal bone loss at 1 year grouped into 2 categories (bone loss >1.5 mm and <= 1.5 mm). Univariate and multivariate regression mixed-effects models were developed to identify variables associated with crestal bone level changes over time. P values <=.05 were considered statistically significant. The study sample was composed of 85 subjects who received 148 implants. The mean change of the crestal bone was 2.1 +/- 1.5 mm (range = -12.5 to 0.5 mm; median = -1.77 mm). In the multivariate model, none of the variables studied were statistically associated with mean crestal bone loss. Among 84 (66.1%) implants with bone loss >1.5 mm within 1 year, no variables were associated with bone loss in the multivariate model. Of the 11 predictor variables evaluated in this study, none were statistically significant with regard to an increased risk for crestal bone loss or for excessive bone loss within the first year after implant placement. C1 [Kim, Sang Y.] INOVA Fairfax Hosp, Falls Church, VA USA. [Dodson, Thomas B.; Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Do, Duy T.; Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Chuang, SK (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. EM sungkiangchuang@gmail.com FU Adirondack Oral & Maxillofacial Surgery (Albany, NY) FX The authors wound like to acknowledge Massachusetts General Hospital, Department of Oral and Maxillofacial Surgery's Education and Research Fund (S.Y.K., D.T.D.) and Center for Applied Clinical Investigation (T.B.D., S.-K.C.), as well as the Massachusetts General Hospital Physicians Organization (S.-K.C., T.B.D.). The authors would also like to thank Adirondack Oral and Maxillofacial Surgery, its clinicians, and staff for allowing access to their patient sample. This project was supported in part by a grant to the Center for Applied Clinical Investigation by Adirondack Oral & Maxillofacial Surgery (Albany, NY). NR 37 TC 0 Z9 0 U1 0 U2 2 PU ALLEN PRESS INC PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 0160-6972 EI 1548-1336 J9 J ORAL IMPLANTOL JI J. Oral Implant. PD OCT PY 2015 VL 41 IS 5 BP 579 EP 585 DI 10.1563/AAID-JOI-D-12-00193 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CT8QR UT WOS:000363081600011 PM 24575757 ER PT J AU Sangji, NF Ramly, EP Kaafarani, HMA Seethala, R Raybould, T Camargo, CA Velmahos, G Masiakos, PT Lee, J AF Sangji, Naveen F. Ramly, Elie P. Kaafarani, Haytham M. A. Seethala, Raghu Raybould, Toby Camargo, Carlos A., Jr. Velmahos, George Masiakos, Peter T. Lee, Jarone TI Health care utilization and charges following the enactment of the 2007 Graduated Drivers Licensing Law in Massachusetts SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Graduated Drivers Licensing laws; Teenage drivers; Health care costs; Health care utilization; Massachusetts ID MOTOR-VEHICLE CRASHES; STATES; POLICIES AB Background: Graduated Drivers Licensing (GDL) programs phase in driving privileges for teenagers. In 2007, Massachusetts implemented a stricter version of the 1998 GDL law, with increased fines and education. This study evaluated the impact of the law on motor vehicle crash (MVC)-related health care utilization and charges. Methods: Massachusetts government and US Census Bureau data were analyzed to compare the rates of MVC-related emergency department (ED) visits and hospital charges before (2002-2006) and after (2007-2011) the 2007 GDL law. Three driver age groups were studied: 16-17 (evaluating the law effect), 18-20 (evaluating the sustainability of the effect), and 25-29 years old (control group). Results: MVC-related ED visits per population decreased after the law for all three age groups (16-17: 2326 to 713; 18-20: 2110 to 1304; 25-29: 1694 to 1228; per 100,000, p < 0.001), but the decrease was greater amongst teenagers (16-17: -69%; 18-20: -38%) compared to the control group (-27%); p < 0.001. MVC-related hospital charges per population also decreased for teenagers but increased for the control group (16-17: $2.70 m to $1.45 m; 18-20: $3.52 m to $2.26 m; 25-29: $1.86 m to $1.92 m; per 100,000, p < 0.001). Conclusions: The 2007 GDL law in Massachusetts was associated with significant decreases in MVC-related health care utilization and hospital charges among teenage drivers. (C) 2015 Elsevier Inc. All rights reserved. C1 [Sangji, Naveen F.; Ramly, Elie P.; Kaafarani, Haytham M. A.; Raybould, Toby; Velmahos, George; Lee, Jarone] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit, Dept Surg, Boston, MA 02114 USA. [Seethala, Raghu] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.; Lee, Jarone] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Masiakos, Peter T.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Lee, J (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM nsangji@partners.org; eramly@partners.org; hkaafarani@partners.org; rseethala@partners.org; traybould@partners.org; ccamargo@partners.org; gvelmahos@partners.org; pmasiakos@partners.org; lee.jarone@mgh.harvard.edu OI Lee, Jarone/0000-0002-4532-8523 NR 17 TC 0 Z9 0 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 0022-3468 EI 1531-5037 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD OCT PY 2015 VL 50 IS 10 BP 1791 EP 1796 DI 10.1016/j.jpedsurg.2015.06.004 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA CU1HI UT WOS:000363271000033 PM 26235531 ER PT J AU Cherayil, BJ AF Cherayil, Bobby J. TI Pathophysiology of Iron Homeostasis during Inflammatory States SO JOURNAL OF PEDIATRICS LA English DT Article ID PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; DISEASE-ACTIVITY; HEPCIDIN EXPRESSION; HORMONE HEPCIDIN; SERUM HEPCIDIN; DOUBLE-BLIND; IN-VIVO; ANEMIA C1 [Cherayil, Bobby J.] Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA. [Cherayil, Bobby J.] Harvard Univ, Sch Med, Boston, MA USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Bldg 114,16th St, Charlestown, MA 02129 USA. EM cherayil@helix.mgh FU National Institute of Allergy and Infectious Diseases [R01 AI089700] FX B.C.'s laboratory is supported by the National Institute of Allergy and Infectious Diseases (R01 AI089700). NR 56 TC 1 Z9 1 U1 3 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2015 VL 167 IS 4 SU S BP S15 EP S19 DI 10.1016/j.jpeds.2015.07.015 PG 5 WC Pediatrics SC Pediatrics GA CU4ZO UT WOS:000363541000004 PM 26364019 ER PT J AU Kleinman, RE AF Kleinman, Ronald E. TI Expert Recommendations on Iron Fortification in Infants SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 [Kleinman, Ronald E.] MassGen Hosp Children, Boston, MA USA. [Kleinman, Ronald E.] Harvard Univ, Sch Med, Boston, MA USA. RP Kleinman, RE (reprint author), Massachusetts Gen Hosp, Dept Pediat, 175 Cambridge St,Suite 578, Boston, MA 02114 USA. EM rkleinman@partners.org NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2015 VL 167 IS 4 SU S BP S48 EP S49 DI 10.1016/j.jpeds.2015.07.021 PG 2 WC Pediatrics SC Pediatrics GA CU4ZO UT WOS:000363541000010 PM 26364026 ER PT J AU Kleinman, RE AF Kleinman, Ronald E. TI Introduction: Recommended Iron Levels for Nutritional Formulas for Infants SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID DEFICIENCY C1 [Kleinman, Ronald E.] MassGen Hosp Children, Boston, MA USA. [Kleinman, Ronald E.] Harvard Univ, Sch Med, Boston, MA USA. RP Kleinman, RE (reprint author), Massachusetts Gen Hosp, Dept Pediat, 175 Cambridge St,Suite 578, Boston, MA 02114 USA. EM rkleinman@partners.org NR 7 TC 0 Z9 0 U1 2 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2015 VL 167 IS 4 SU S BP S1 EP S2 DI 10.1016/j.jpeds.2015.07.012 PG 2 WC Pediatrics SC Pediatrics GA CU4ZO UT WOS:000363541000001 PM 26364018 ER PT J AU Vanderhoof, JA Kleinman, RE AF Vanderhoof, Jon A. Kleinman, Ronald E. TI Iron Requirements for Infants with Cow Milk Protein Allergy SO JOURNAL OF PEDIATRICS LA English DT Article ID BREAST-FED INFANTS; FOOD ALLERGY; DEFICIENCY ANEMIA; YOUNG-CHILDREN; PROCTOCOLITIS; COLITIS; SUPPLEMENTATION; PREVALENCE; DIAGNOSIS; ABSORPTION C1 [Vanderhoof, Jon A.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Vanderhoof, Jon A.] Mead Johnson Nutr, Glenview, IL USA. [Kleinman, Ronald E.] MassGen Hosp Children, Boston, MA USA. [Kleinman, Ronald E.] Harvard Univ, Sch Med, Boston, MA USA. RP Kleinman, RE (reprint author), Massachusetts Gen Hosp, Dept Pediat, 175 Cambridge St,Suite 578, Boston, MA 02114 USA. EM rkleinman@partners.org NR 46 TC 0 Z9 0 U1 2 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2015 VL 167 IS 4 SU S BP S36 EP S39 DI 10.1016/j.jpeds.2015.07.019 PG 4 WC Pediatrics SC Pediatrics GA CU4ZO UT WOS:000363541000008 PM 26364024 ER PT J AU Choueiri, TK Motzer, RJ AF Choueiri, Toni K. Motzer, Robert J. TI The Right Drug for the Right Patient: Navigating Systemic Therapy Options in Metastatic Renal Cell Carcinoma and Future Directions SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material ID SUNITINIB C1 [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Choueiri, Toni K.] Brigham & Womens Hosp, Kidney Canc Ctr, Boston, MA 02115 USA. [Choueiri, Toni K.] DF HCC, Kidney Canc Program, Boston, MA USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA USA. [Choueiri, Toni K.] Kidney Canc Assoc, Med & Sci Steering Comm, Evanston, IL USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2015 VL 13 IS 10 BP 1168 EP 1170 PG 3 WC Oncology SC Oncology GA CU3OF UT WOS:000363434000002 PM 26483056 ER PT J AU Nabors, LB Portnow, J Ammirati, M Baehring, J Brem, H Brown, P Butowski, N Chamberlain, MC Fenstermaker, RA Friedman, A Gilbert, MR Hattangadi-Gluth, J Holdhoff, M Junck, L Kaley, T Lawson, R Loeffler, JS Lovely, MP Moots, PL Mrugala, MM Newton, HB Parney, I Raizer, JJ Recht, L Shonka, N Shrieve, DC Sills, AK Swinnen, LJ Tran, D Tran, N Vrionis, FD Weiss, S Wen, PY McMillian, N Engh, AM AF Nabors, Louis Burt Portnow, Jana Ammirati, Mario Baehring, Joachim Brem, Henry Brown, Paul Butowski, Nicholas Chamberlain, Marc C. Fenstermaker, Robert A. Friedman, Allan Gilbert, Mark R. Hattangadi-Gluth, Jona Holdhoff, Matthias Junck, Larry Kaley, Thomas Lawson, Ronald Loeffler, Jay S. Lovely, Mary P. Moots, Paul L. Mrugala, Maciej M. Newton, Herbert B. Parney, Ian Raizer, Jeffrey J. Recht, Lawrence Shonka, Nicole Shrieve, Dennis C. Sills, Allen K., Jr. Swinnen, Lode J. Tran, David Tran, Nam Vrionis, Frank D. Weiss, Stephanie Wen, Patrick Yung McMillian, Nicole Engh, Anita M. TI Central Nervous System Cancers, Version 1.2015 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID LOW-GRADE GLIOMAS; NEWLY-DIAGNOSED GLIOBLASTOMA; INTENSITY-MODULATED RADIOTHERAPY; PHASE-II TRIAL; THERAPY-ONCOLOGY-GROUP; RADIATION-THERAPY; ADJUVANT TEMOZOLOMIDE; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; PLUS CONCOMITANT AB The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update. This article outlines the data and provides insight into panel decisions regarding adjuvant radiation and chemotherapy treatment options for high-risk newly diagnosed low-grade gliomas and glioblastomas. Additionally, it describes the panel's assessment of new data and the ongoing debate regarding the use of alternating electric field therapy for high-grade gliomas. C1 [Nabors, Louis Burt] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35233 USA. [Portnow, Jana] City Hope Comprehens Canc Ctr, New York, NY USA. [Ammirati, Mario; Newton, Herbert B.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Ammirati, Mario; Newton, Herbert B.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Baehring, Joachim] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Brem, Henry; Holdhoff, Matthias; Swinnen, Lode J.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Brown, Paul; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Butowski, Nicholas] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Chamberlain, Marc C.; Mrugala, Maciej M.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Fenstermaker, Robert A.] Roswell Pk Canc Inst, Buffalo, NY USA. [Friedman, Allan] Duke Canc Inst, Durham, NC USA. [Hattangadi-Gluth, Jona] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Junck, Larry] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Kaley, Thomas] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Lawson, Ronald] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Loeffler, Jay S.] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA. [Lovely, Mary P.] Amer Brain Tumor Assoc, Chicago, IL USA. [Moots, Paul L.; Sills, Allen K., Jr.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Parney, Ian] Mayo Clin, Canc Ctr, Rochester, MN USA. [Raizer, Jeffrey J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Recht, Lawrence] Stanford Canc Inst, Stanford, CA USA. [Shonka, Nicole] Fred & Pamela Buffet Canc Ctr, Omaha, NE USA. [Shrieve, Dennis C.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Tran, David] Barnes Jewish Hosp, Siteman Canc Ctr, Louis, MO USA. [Tran, David] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Tran, Nam; Vrionis, Frank D.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Weiss, Stephanie] Fox Chase Canc Ctr, Boston, MA USA. [Wen, Patrick Yung] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [McMillian, Nicole; Engh, Anita M.] City Hope Comprehens Canc Ctr, New York, NY USA. RP Nabors, LB (reprint author), Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35233 USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU Eisai; Bristol-Myers Squibb; Genentech BioOncology; Merck; Novartis Oncology; Novocure; Boehringer Ingelheim Pharmaceuticals, Inc. FX Supported by an educational grant from Eisai; a contribution from Exelixis Inc.; educational grants from Bristol-Myers Squibb, Genentech BioOncology, Merck, Novartis Oncology, Novocure; and by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. NR 75 TC 7 Z9 9 U1 4 U2 10 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2015 VL 13 IS 10 BP 1191 EP 1202 PG 12 WC Oncology SC Oncology GA CU3OF UT WOS:000363434000005 PM 26483059 ER PT J AU Alvarnas, JC Brown, PA Aoun, P Ballen, KK Barta, SK Borate, U Boyer, MW Burke, PW Cassaday, R Castro, JE Coccia, PF Coutre, SE Damon, LE DeAngelo, DJ Douer, D Frankfurt, O Greer, JP Johnson, RA Kantarjian, HM Klisovic, RB Kupfer, G Litzow, M Liu, A Rao, AV Shah, B Uy, GL Wang, ES Zelenetz, AD Gregory, K Smith, C AF Alvarnas, Joseph C. Brown, Patrick A. Aoun, Patricia Ballen, Karen Kuhn Barta, Stefan K. Borate, Uma Boyer, Michael W. Burke, Patrick W. Cassaday, Ryan Castro, Januario E. Coccia, Peter F. Coutre, Steven E. Damon, Lloyd E. DeAngelo, Daniel J. Douer, Dan Frankfurt, Olga Greer, John P. Johnson, Robert A. Kantarjian, Hagop M. Klisovic, Rebecca B. Kupfer, Gary Litzow, Mark Liu, Arthur Rao, Arati V. Shah, Bijal Uy, Geoffrey L. Wang, Eunice S. Zelenetz, Andrew D. Gregory, Kristina Smith, Courtney TI Acute Lymphoblastic Leukemia, Version 2.2015 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID MINIMAL RESIDUAL DISEASE; STEM-CELL TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; CHILDRENS-ONCOLOGY-GROUP; ABL KINASE DOMAIN; CHROMOSOME-POSITIVE LEUKEMIAS; ACUTE LYMPHOCYTIC-LEUKEMIA; POLYMERASE-CHAIN-REACTION; RANDOMIZED CONTROLLED-TRIAL; SULFATE LIPOSOME INJECTION AB Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org. C1 [Alvarnas, Joseph C.; Aoun, Patricia] City Hope Comprehens Canc Ctr, Cold Spring Harbor, NY 11724 USA. [Brown, Patrick A.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Sidney, BC, Canada. [Ballen, Karen Kuhn] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Barta, Stefan K.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Borate, Uma] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Boyer, Michael W.] Huntsman Canc Inst, Salt Lake City, UT USA. [Boyer, Michael W.] Univ Utah, Salt Lake City, UT 84112 USA. [Burke, Patrick W.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Cassaday, Ryan] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Castro, Januario E.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Coccia, Peter F.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Coutre, Steven E.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Damon, Lloyd E.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA USA. [Douer, Dan] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Frankfurt, Olga] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Greer, John P.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Johnson, Robert A.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Klisovic, Rebecca B.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Klisovic, Rebecca B.] James Canc Hosp, Columbus, OH USA. [Klisovic, Rebecca B.] Solove Res Inst, Columbus, OH USA. [Kupfer, Gary] Smilow Canc Hosp, Yale Canc Ctr, New York, NY USA. [Litzow, Mark] Mayo Clin, Ctr Canc, Rochester, MN USA. [Liu, Arthur] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Rao, Arati V.] Duke Canc Inst, Durham, NC USA. [Shah, Bijal] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Uy, Geoffrey L.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Uy, Geoffrey L.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Wang, Eunice S.] Roswell Pk Canc Inst, Buffalo, NY USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Gregory, Kristina; Smith, Courtney] NCCN, New York, NY USA. RP Alvarnas, JC (reprint author), City Hope Comprehens Canc Ctr, Cold Spring Harbor, NY 11724 USA. RI Klisovic, Rebecca/E-3401-2011 NR 167 TC 5 Z9 6 U1 2 U2 10 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2015 VL 13 IS 10 BP 1240 EP 1279 PG 40 WC Oncology SC Oncology GA CU3OF UT WOS:000363434000010 PM 26483064 ER PT J AU Gliklich, RE Metson, R AF Gliklich, Richard E. Metson, Ralph TI Techniques for Outcomes Research in Chronic Sinusitis SO LARYNGOSCOPE LA English DT Article ID HEALTH SURVEY QUESTIONNAIRE; SF-36; MANAGEMENT AB Accurate assessment of patient outcome after sinus surgery requires the collection of valid and reliable data. Symptom-based surveys were administered in a prospective manner to 104 patients with chronic sinusitis. Test-retest reliability for the Chronic Sinusitis Survey based on duration of symptoms (0.86, P<.0001) was superior to that for a similar survey based on severity of symptoms (0.57, P<.0001). Results of the Chronic Sinusitis Survey also correlated significantly with subscales of a general health assessment in the extent to which chronic sinusitis limits physical activity (0.40, P<.01), interferes with work or other activities (0.36, P<.01), and affects patient perception of bodily pain (0.46, P<.001). The Chronic Sinusitis Survey is an efficient and reliable method to follow health status and health-related quality of life outcomes in patients with chronic sinusitis. C1 [Gliklich, Richard E.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Clin Outcomes Res Unit, Boston, MA 02114 USA. [Gliklich, Richard E.; Metson, Ralph] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Gliklich, RE (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2015 VL 125 IS 10 BP 2238 EP 2241 DI 10.1002/lary.25276 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CU2XF UT WOS:000363386300012 PM 26390386 ER PT J AU Scangas, GA Ishman, SL Bergmark, RW Cunningham, MJ Sedaghat, AR AF Scangas, George A. Ishman, Stacey L. Bergmark, Regan W. Cunningham, Michael J. Sedaghat, Ahmad R. TI Emergency Department Presentation for Uncomplicated Acute Rhinosinusitis Is Associated With Poor Access to Healthcare SO LARYNGOSCOPE LA English DT Article DE Health policy; outcomes; cost effectiveness; clinical; allergy; rhinology ID CLINICAL-PRACTICE GUIDELINE; ACUTE BACTERIAL RHINOSINUSITIS; INSURANCE STATUS; SOCIOECONOMIC DISPARITIES; SINUSITIS; REFORM; MASSACHUSETTS; CHILDREN; CANCER; SURVIVAL AB Objectives/Hypothesis: Uncomplicated acute rhinosinusitis (ARS) is most appropriately managed in an outpatient clinic setting. Some ARS patients present to emergency departments (EDs) for care. We investigates factors associated with ARS presentation to EDs versus outpatient settings. Study Design: Cross-sectional study. Methods: A total of 17,122,551 pediatric and adult patient visits from the 2009 and 2010 National Ambulatory Medical Care and National Hospital Ambulatory Medical Care Surveys for ARS were identified. Patients with ARS complications were excluded. Univariate and multivariate associations identified demographic and socioeconomic characteristics of ARS patients independently associated with ED presentation. Temperature >100 degrees F was used as a proxy for ARS severity. Results: Patients with Medicaid (odds ratio [OR] 10.82, P < .001) or no insurance (OR 9.14, P < .001) more likely presented to EDs when compared to patients with private insurance or Medicare. Independently, black patients (OR 6.01, P < .001) more likely presented to EDs when compared to while or Hispanic patients. No significant association was seen with metropolitan or socioeconomic status based upon the patients home zip code. Conclusions: Presentation of ARS patients to EDs is associated with health insurance type and patient race independent of socioeconomic status. Healthcare access appears to be a primary determinant of whether patients present to an ED or outpatient setting for this common health problem. The association between race and ED presentation suggests cultural underpinnings requiring further characterization. Reducing barriers to care, for example through broader health insurance coverage, may enhance access to outpatient care providers and decrease costs associated with unnecessary ED presentation. C1 [Scangas, George A.; Bergmark, Regan W.; Sedaghat, Ahmad R.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Scangas, George A.; Bergmark, Regan W.; Cunningham, Michael J.; Sedaghat, Ahmad R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Ishman, Stacey L.] Cincinnati Childrens Hosp Med Ctr, Div Otolaryngol Head & Neck Surg, Cincinnati, OH 45229 USA. [Ishman, Stacey L.] Cincinnati Childrens Hosp Med Ctr, Div Pulm Med, Cincinnati, OH 45229 USA. [Ishman, Stacey L.] Univ Cincinnati, Dept Otolaryngol Head & Neck Surg, Cincinnati, OH USA. [Cunningham, Michael J.] Boston Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu NR 31 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2015 VL 125 IS 10 BP 2253 EP 2258 DI 10.1002/lary.25230 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CU2XF UT WOS:000363386300016 PM 25781423 ER PT J AU Varvares, MA Poti, S Kenyon, B Christopher, K Walker, RJ AF Varvares, Mark A. Poti, Shannon Kenyon, Bianca Christopher, Kara Walker, Ronald J. TI Surgical Margins and Primary Site Resection in Achieving Local Control in Oral Cancer Resections SO LARYNGOSCOPE LA English DT Article DE Oral cancer; tongue cancer; surgical margins ID SQUAMOUS-CELL CARCINOMA; FROZEN-SECTIONS; NECK-CANCER; OROPHARYNGEAL CANCER; CUT-THROUGH; HEAD; TONGUE; SURVIVAL; SURGERY; IMPACT AB Objectives/Hypothesis: Evaluate effectiveness of resection of oral cavity cancer with a standardized approach for margin evaluation. Primary end points were local control and survival. Study Design: Retrospective, nonrandomized, single institution. Methods: One hundred eight patients who underwent surgery for oral cancer were evaluated using specific anatomical pathology criteria. Frozen section was performed with the surgeon and pathologist agreeing where on the specimen the frozen sections should be taken in most cases. Results: Ninety-one patients (84.3%) had frozen sections taken from the specimen, eight from the tumor bed, and nine had none taken at the time of surgery. Overall local recurrence rate was 18.5%, 25% in patients who had margins taken from the tumor bed and 17.6% when taken from the specimen. Twenty-nine patients had margins >= 5 mm, 53 <5 mm and clear, and 14 positive re-resected to negative with local recurrence rates of 3.4%, 26.4%, and 28.6%, respectively. The radial distance of the resection margin was shown to have an impact on overall survival (hazard ratio [HR] = 3.59, 95% confidence interval [CI]= 1.12-11.57), disease-free survival (HR = 7.00, 95% CI = 1.89-25.95), and local recurrence-free survival (HR = 28.80, 95% CI = 3.00-276.82). Conclusions: Assessing margins from the resection specimen rather than the tumor bed consistently predicts local control. There is a statistical improvement in local control, disease-free, and overall survival with increasing radial margin distance from the tumor, and 5 mm should be agreed upon as the definition of a clear resection margin. Frozen sections can be used to revise positive or close resection margins intraoperatively with improved outcomes. C1 [Varvares, Mark A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Varvares, Mark A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Poti, Shannon] Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Kenyon, Bianca] Loyola Sch Med, Dept Surg, Chicago, IL USA. [Christopher, Kara] St Louis Univ, Ctr Canc, St Louis, MO 63103 USA. [Walker, Ronald J.] St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63103 USA. RP Varvares, MA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM mark_varvares@meei.harvard.edu NR 34 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2015 VL 125 IS 10 BP 2298 EP 2307 DI 10.1002/lary.25397 PG 10 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CU2XF UT WOS:000363386300024 PM 26011037 ER PT J AU Noij, KS Remenschneider, AK Kozin, ED Puram, S Herrmann, B Cohen, M Cunnane, MB Lee, DJ AF Noij, Kimberley S. Remenschneider, Aaron K. Kozin, Elliott D. Puram, Sidharth Herrmann, Barbara Cohen, Michael Cunnane, Mary Beth Lee, Daniel J. TI Direct Parasagittal Magnetic Resonance Imaging of the Internal Auditory Canal to Determine Cochlear or Auditory Brainstem Implant Candidacy in Children SO LARYNGOSCOPE LA English DT Editorial Material DE Cochlear implant; auditory brainstem implant; magnetic resonance imaging; internal auditory canal; imaging technique ID SENSORINEURAL HEARING-LOSS; PREOPERATIVE EVALUATION; COMPUTED-TOMOGRAPHY; NERVE DEFICIENCY; COCHLEOVESTIBULAR NERVE; INNER-EAR; CT C1 [Noij, Kimberley S.; Remenschneider, Aaron K.; Kozin, Elliott D.; Puram, Sidharth; Herrmann, Barbara; Cohen, Michael; Cunnane, Mary Beth; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Noij, Kimberley S.; Remenschneider, Aaron K.; Kozin, Elliott D.; Puram, Sidharth; Herrmann, Barbara; Cohen, Michael; Cunnane, Mary Beth; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM dan-iel_lee@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 NR 21 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2015 VL 125 IS 10 BP 2382 EP 2385 DI 10.1002/lary.25228 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CU2XF UT WOS:000363386300038 PM 25778542 ER PT J AU Zeuren, R Biagini, A Grewal, RK Randolph, GW Kamani, D Sabra, MM Shaha, AR Tuttle, RM AF Zeuren, Rebecca Biagini, Agnese Grewal, Ravinder K. Randolph, Gregory W. Kamani, Dipti Sabra, Mona M. Shaha, Ashok R. Tuttle, R. Michael TI RAT Thyroid Bed Uptake After Total Thyroidectomy: A Novel SPECT-CT Anatomic Classification System SO LARYNGOSCOPE LA English DT Article DE radioactive iodine; remnant ablation; thyroidectomy; thyroid cancer; RRA; postoperative Tg ID POSTOPERATIVE THYROGLOBULIN LEVELS; POSTABLATION I-131 SCINTIGRAPHY; RECURRENT LARYNGEAL NERVE; LYMPH-NODE DISSECTION; SERUM THYROGLOBULIN; PARATHYROID-GLANDS; CANCER; CARCINOMA; MANAGEMENT; ABLATION AB Objective: Recent, more selective use of radioactive iodine (RAI) has led to reevaluation of the clinical importance of achieving complete total thyroidectomy with minimal residual normal thyroid tissue. We utilize the improved localization by post-RAI remnant ablation, single photon emission computerized tomography-computed tomography (SPECT-CT) to define specific anatomic sites of residual RAI-uptake foci after total thyroidectomy for differentiated thyroid cancer (DTC) and to provide a novel classification system relating uptake to thyroid anatomy and preservation of adjacent neural structures. Study Design: Retrospective. Method: Radioactive iodine-uptake foci in thyroid bed were localized by SPECT/CT imaging at the time of RAI remnant ablation in 141 DTC patients undergoing total thyroidectomy. Results: Minimal residual RAI uptake (median 0.32% at 24 hours) in the thyroid bed was detected by diagnostic planar whole body scans in 93% and by posttherapy SPECT/CT imaging in 99% of subjects. Discrete RAI uptake foci were identified on the SPECT/CT imaging at Berry's ligament (87%), at superior thyroid poles (79%), in paratracheal-lobar regions (67%), in isthmus-region (51%), and in pyramidal lobe (16%). Despite the residual foci, the nonstimulated thyroglobulin (Tg) prior to remnant ablation (with a median thyroid-stimulating hormone of 0.36 m IU/L) was <0.6 ng/mL in 53% and <1 ng/mL in 73% of cases. Conclusion: After extracapsular total thyroidectomy, highly sensitive detection tools identify microscopic residual RAI avid foci in thyroid bed in the majority of patients. These foci can be classified as 1) neural-related and 2) capsule-related. These common residual foci have no relationship to postoperative Tg, suggesting that attempts at radical removal of thyroid tissue in these locations may not be warranted. C1 [Zeuren, Rebecca; Biagini, Agnese; Sabra, Mona M.; Shaha, Ashok R.; Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, Dept Endocrinol Serv, New York, NY 10021 USA. [Grewal, Ravinder K.] Mem Sloan Kettering Canc Ctr, Dept Nucl Med, New York, NY 10021 USA. [Shaha, Ashok R.] Mem Sloan Kettering Canc Ctr, Dept Head & Neck Surg, New York, NY 10021 USA. [Randolph, Gregory W.; Kamani, Dipti] Harvard Univ, Massachusetts Eye & Ear Infirm, Div Thyroid & Parathyroid Surg, Otolaryngol, Boston, MA 02215 USA. [Randolph, Gregory W.] Harvard Univ, Sch Med, Dept Surg Oncol, Massachusetts Gen Hosp, Boston, MA USA. RP Randolph, GW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolatyngol, Div Thyroid & Parathyroid Surg, 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu FU NCI NIH HHS [P30 CA008748] NR 40 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2015 VL 125 IS 10 BP 2417 EP 2424 DI 10.1002/lary.25295 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CU2XF UT WOS:000363386300046 PM 25891354 ER PT J AU Huck, A Pozdnyakova, O Brunner, A Higgins, JM Fathi, AT Hasserjian, RP AF Huck, Amelia Pozdnyakova, Olga Brunner, Andrew Higgins, John M. Fathi, Amir T. Hasserjian, Robert P. TI Prior cytopenia predicts worse clinical outcome in acute myeloid leukemia SO LEUKEMIA RESEARCH LA English DT Article DE Acute myeloid leukemia; Myelodysplastic syndrome; Cytopenia ID MYELODYSPLASIA-RELATED CHANGES; INDEPENDENT PROGNOSTIC RELEVANCE; CLONAL HEMATOPOIESIS; UNEXPLAINED ANEMIA; AML; CLASSIFICATION; PREVALENCE; DIAGNOSIS; SYSTEM; OLDER AB The prognosis of acute myeloid leukemia (AML) is influenced by both disease-intrinsic and patient-related factors. In particular, AML following myelodysplastic syndrome (MDS) (AML with myelodysplasia-related changes, AML-MRC) has a poor prognosis. We hypothesized that patients with cytopenias prior to AML, but no known prior MDS, may share biologic features with AML-MRC. We evaluated 140 AML patients without prior MDS who had complete blood count (CBC) data available 6-36 months prior to their diagnosis. Cytopenia, defined as clinically unexplained thrombocytopenia or macrocytic anemia, was present in 29/140 (21%) patients. Compared to non-cytopenic patients, AML patients with prior cytopenia were older and more often met morphologic or cytogenetic criteria for AML-MRC. Prior cytopenia was associated with shorter survival in patients with intermediate-risk cytogenetics (median OS 4.2 versus 24.1 months, p < 0.0001), but not in patients with adverse-risk cytogenetics (median OS 4.4 versus 6.0 months, p = 0.57). Prior thrombocytopenia, but not macrocytic anemia, was significantly associated with shorter overall survival (p = 0.01) independent of treatment approach, karyotype risk, and age on multivariable analysis. Our data suggest that AML patients with prior cytopenias have features similar to AML-MRC, and in particular support the use of prior unexplained thrombocytopenia as an independent marker of high-risk disease. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Huck, Amelia; Higgins, John M.; Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pozdnyakova, Olga] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Brunner, Andrew; Fathi, Amir T.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 224,55 Fruit St, Boston, MA 02114 USA. EM rhasserjian@partners.org NR 22 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD OCT PY 2015 VL 39 IS 10 BP 1034 EP 1040 DI 10.1016/j.leukres.2015.06.012 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA CU3LT UT WOS:000363427600005 PM 26220865 ER PT J AU Weisberg, E Halilovic, E Cooke, VG Nonami, A Ren, T Sanda, T Simkin, I Yuan, J Antonakos, B Barys, L Ito, M Stone, R Galinsky, I Cowens, K Nelson, E Sattler, M Jeay, S Wuerthner, JU McDonough, SM Wiesmann, M Griffin, JD AF Weisberg, Ellen Halilovic, Ensar Cooke, Vesselina G. Nonami, Atsushi Ren, Tao Sanda, Takaomi Simkin, Irene Yuan, Jing Antonakos, Brandon Barys, Louise Ito, Moriko Stone, Richard Galinsky, Ilene Cowens, Kristen Nelson, Erik Sattler, Martin Jeay, Sebastien Wuerthner, Jens U. McDonough, Sean M. Wiesmann, Marion Griffin, James D. TI Inhibition of Wild-Type p53-Expressing AML by the Novel Small Molecule HDM2 Inhibitor CGM097 SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TUMOR-SUPPRESSOR PATHWAY; BH3-ONLY PROTEINS PUMA; P53 PATHWAY; DNA-DAMAGE; IN-VIVO; PEPTIDE INHIBITORS; FUNCTIONAL ASSAY; MDM2 INHIBITOR; CANCER-CELLS AB The tumor suppressor p53 is a key regulator of apoptosis and functions upstream in the apoptotic cascade by both indirectly and directly regulating Bcl-2 family proteins. In cells expressing wild-type (WT) p53, the HDM2 protein binds to p53 and blocks its activity. Inhibition of HDM2: p53 interaction activates p53 and causes apoptosis or cell-cycle arrest. Here, we investigated the ability of the novel HDM2 inhibitor CGM097 to potently and selectively kill WT p53-expressing AML cells. The antileukemic effects of CGM097 were studied using cell-based proliferation assays (human AML cell lines, primary AML patient cells, and normal bone marrow samples), apoptosis, and cell-cycle assays, ELISA, immunoblotting, and an AML patient-derived in vivo mouse model. CGM097 potently and selectively inhibited the proliferation of human AML cell lines and the majority of primary AML cells expressing WT p53, but not mutant p53, in a target-specific manner. Several patient samples that harbored mutant p53 were comparatively unresponsive to CGM097. Synergy was observed when CGM097 was combined with FLT3 inhibition against oncogenic FLT3-expressing cells cultured both in the absence as well as the presence of cytoprotective stromal-secreted cytokines, as well as when combined with MEK inhibition in cells with activated MAPK signaling. Finally, CGM097 was effective in reducing leukemia burden in vivo. These data suggest that CGM097 is a promising treatment for AML characterized as harboring WT p53 as a single agent, as well as in combination with other therapies targeting oncogene-activated pathways that drive AML. (C) 2015 AACR. C1 [Weisberg, Ellen; Nonami, Atsushi; Sanda, Takaomi; Stone, Richard; Galinsky, Ilene; Cowens, Kristen; Nelson, Erik; Sattler, Martin; McDonough, Sean M.; Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Halilovic, Ensar; Cooke, Vesselina G.; Yuan, Jing; Antonakos, Brandon] Novartis Inst Biomed Res, Cambridge, MA USA. [Ren, Tao] Harvard Univ, Sch Med, Natl Screening Lab, Reg Ctr Excellence Biodef & Emerging Infect Dis R, Boston, MA USA. [Simkin, Irene] Boston Univ, Sch Med, Mol Genet Core, Boston, MA 02118 USA. [Barys, Louise; Ito, Moriko; Jeay, Sebastien; Wuerthner, Jens U.; Wiesmann, Marion] Novartis Inst Biomed Res, Basel, Switzerland. RP Weisberg, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM ellen_weisberg@dfci.harvard.edu; james_griffin@dfci.harvard.edu FU NIH [CA66996, CA134660-03] FX J.D. Griffin received NIH grant CA66996 and the work of all authors (with the exception of employees of Novartis Pharmaceuticals and M. Sattler) related to CGM097 was supported by this grant. M. Sattler received NIH grant CA134660-03. NR 50 TC 5 Z9 5 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2015 VL 14 IS 10 BP 2249 EP 2259 DI 10.1158/1535-7163.MCT-15-0429 PG 11 WC Oncology SC Oncology GA CU3EA UT WOS:000363405600009 PM 26206331 ER PT J AU Xu, CX Buczkowski, KA Zhang, YX Asahina, H Beauchamp, EM Terai, H Li, YY Meyerson, M Wong, KK Hammerman, PS AF Xu, Chunxiao Buczkowski, Kevin A. Zhang, Yanxi Asahina, Hajime Beauchamp, Ellen M. Terai, Hideki Li, Yvonne Y. Meyerson, Matthew Wong, Kwok-kin Hammerman, Peter S. TI NSCLC Driven by DDR2 Mutation Is Sensitive to Dasatinib and JQ1 Combination Therapy SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; LUNG-CANCER; KINASE; ADENOCARCINOMA; EXPRESSION; INHIBITION; PHOSPHORYLATION; DIFFERENTIATION; METASTASIS; RECEPTOR-2 AB Genetically engineered mouse models of lung cancer have demonstrated an important role in understanding the function of novel lung cancer oncogenes and tumor-suppressor genes identified in genomic studies of human lung cancer. Furthermore, these models are important platforms for preclinical therapeutic studies. Here, we generated a mouse model of lung adenocarcinoma driven by mutation of the discoidin domain receptor 2 (DDR2) gene combined with loss of TP53. DDR2(L63V); TP53(L/L) mice developed poorly differentiated lung adenocarcinomas in all transgenic animals analyzed with a latency of 40 to 50 weeks and a median survival of 67.5 weeks. Mice expressing wild-type DDR2 with combined TP53 loss did not form lung cancers. DDR2(L63V); TP53(L/L) tumors displayed robust expression of DDR2 and immunohistochemical markers of lung adenocarcinoma comparable with previously generated models, though also displayed concomitant expression of the squamous cell markers p63 and SOX2. Tumor-derived cell lines were not solely DDR2 dependent and displayed upregulation of and partial dependence on MYCN. Combined treatment with the multitargeted DDR2 inhibitor dasatinib and BET inhibitor JQ1 inhibited tumor growth in vitro and in vivo. Together, these results suggest that DDR2 mutation can drive lung cancer initiation in vivo and provide a novel mouse model for lung cancer therapeutics studies. (C) 2015 AACR. C1 [Xu, Chunxiao; Buczkowski, Kevin A.; Zhang, Yanxi; Asahina, Hajime; Beauchamp, Ellen M.; Terai, Hideki; Li, Yvonne Y.; Meyerson, Matthew; Wong, Kwok-kin; Hammerman, Peter S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Xu, Chunxiao; Zhang, Yanxi; Asahina, Hajime; Wong, Kwok-kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. [Li, Yvonne Y.; Meyerson, Matthew; Hammerman, Peter S.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Meyerson, Matthew] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. RP Hammerman, PS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM kwong1@partners.org; peter_hammerman@dfci.harvard.edu FU United against Lung Cancer; Susan Spooner Research Fund; NIH [NCI P01 CA154303]; NCI [K08 CA163677] FX This work was supported in part by United against Lung Cancer and Susan Spooner Research Fund (to K.-K. Wong); NIH grants NCI P01 CA154303 (to K.- K. Wong and M. Meyerson); and NCI K08 CA163677 (to P.S. Hammerman). NR 36 TC 2 Z9 2 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2015 VL 14 IS 10 BP 2382 EP 2389 DI 10.1158/1535-7163.MCT-15-0077 PG 8 WC Oncology SC Oncology GA CU3EA UT WOS:000363405600022 PM 26206333 ER PT J AU Batth, IS Yun, HY Kumar, AP AF Batth, Izhar Singh Yun, Huiyoung Kumar, Addankl P. TI Recepteur d'Origine Nantais (RON), More Than a Kinase: Role in Castrate-Resistant Prostate Cancer SO MOLECULAR CARCINOGENESIS LA English DT Article DE prostate cancer; castrate resistance; receptor tyrosine kinase; RON ID MACROPHAGE-STIMULATING PROTEIN; ANDROGEN RECEPTOR; TYROSINE KINASE; CELL-LINE; DIFFERENTIAL EXPRESSION; MESENCHYMAL TRANSITION; INHIBITOR BMS-777607; ALTERED EXPRESSION; TUMOR-GROWTH; LUNG-CANCER AB Prostate cancer (PCA) is the second leading cause of cancer-related deaths in men in the United States. It is natural for a hormone-driven malignancy such as prostate cancer that androgen deprivation therapy (ADT) would be the preferred treatment for clinical disease management. However, after initial treatment response a vast majority of patients develop metastatic castrate-resistant prostate cancer (CRPC), which is fatal. While great headway has been made to understand the possible mechanisms that drive castrate-resistant disease, a bonafide cure remains elusive. Reactivation of androgen receptor (AR) signaling partly contributes to the emergence of CRPC. Here we briefly examine some of the known mechanisms of AR reactivation including intratumoral synthesis of androgens, modulation of AR coregulators, and AR variants with constitutive activity as well as activation of receptor tyrosine kinases. We primarily focus on the emerging dual function of the receptor tyrosine kinase (recepteur d'origine nantais; RON) as a traditional tyrosine kinase and transcription factor. We further discuss activation of RON as an alternate mechanism in the development of CRPC and available therapeutic approaches for clinical management of CRPC by combined inhibition of RON and AR. (C) 2015 Wiley Periodicals, Inc. C1 [Batth, Izhar Singh; Kumar, Addankl P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Yun, Huiyoung; Kumar, Addankl P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Kumar, Addankl P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Kumar, Addankl P.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Kumar, Addankl P.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kumar, AP (reprint author), Dept Urol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 110 TC 2 Z9 2 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 2015 VL 54 IS 10 BP 937 EP 946 DI 10.1002/mc.22354 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA CU0PW UT WOS:000363220600001 PM 26152593 ER PT J AU Hambright, HG Batth, IS Xie, JP Ghosh, R Kumar, AP AF Hambright, Heather G. Batth, Izhar Singh Xie, Jianping Ghosh, Rita Kumar, Addanki Pratap TI Palmatine Inhibits Growth and Invasion in Prostate Cancer Cell: Potential Role for rpS6/NF kappa B/FLIP SO MOLECULAR CARCINOGENESIS LA English DT Article DE palmatine; prostate cancer; rpS6 ID AMURENSE BARK EXTRACT; TRANSGENIC ADENOCARCINOMA; NEXRUTINE; INVOLVEMENT; EXPRESSION; BERBERINE; NETWORK; PROTEIN; MODEL; AXIS AB Novel agents are desperately needed for improving the quality of life and 5-year survival to more than 30% for metastatic castrate-resistant prostate cancer. Previously we showed that Nexrutine, Phellodendron amurense bark extract, inhibits prostate tumor growth in vitro and in vivo. Subsequently using biochemical fractionation we identified butanol fraction contributes to the observed biological activities. We report here that palmatine, which is present in the butanol fraction, selectively inhibits growth of prostate cancer cells without significant effect on non-tumorigenic prostate epithelial cells. By screening receptor tyrosine kinases in a protein kinase array, we identified ribosomal protein S6, a downstream target of p70S6K and the Akt/ mTOR signaling cascade as a potential target. We further show that palmatine treatment is associated with decreased activation of NF and its downstream target gene FLIP. These events led to inhibition of invasion. Similar results were obtained using parent extract Nexrutine (Nx) suggesting that palmatine either in the purified form or as one of the components in Nx is a potent cytotoxic agent with tumor invasion inhibitory properties. Synergistic inhibition of rpS6/NF kappa B/FLIP axis with palmatine may have therapeutic potential for the treatment of prostate cancer and possibly other malignancies with their constitutive activation. These data support a biological link between rpS6/NF kappa B/FLIP in mediating palmatine-induced inhibitory effects and warrants additional preclinical studies to test its therapeutic efficacy. (C) 2014 Wiley Periodicals, Inc. C1 [Hambright, Heather G.; Batth, Izhar Singh; Xie, Jianping; Ghosh, Rita; Kumar, Addanki Pratap] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Ghosh, Rita; Kumar, Addanki Pratap] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Pharmacol, San Antonio, TX 78229 USA. [Ghosh, Rita; Kumar, Addanki Pratap] Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. [Kumar, Addanki Pratap] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kumar, AP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. FU Veterans Affairs-Merit Award [I01 BX 000766-01]; National Cancer Institute [1RO1 CA 135451, R21 CA 137578, RO1 CA 149516]; Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio through National Cancer Institute [2P30 CA 054174-17] FX Grant sponsor: Veterans Affairs-Merit Award; Grant number: I01 BX 000766-01; Grant sponsor: National Cancer Institute; Grant numbers: 1RO1 CA 135451; R21 CA 137578; RO1 CA 149516; Grant sponsor: Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio through National Cancer Institute; Grant number: 2P30 CA 054174-17 NR 27 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 2015 VL 54 IS 10 BP 1227 EP 1234 DI 10.1002/mc.22192 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA CU0PW UT WOS:000363220600026 PM 25043857 ER PT J AU Kelly, TN Raj, D Rahman, M Kretzler, M Kallem, RR Ricardo, AC Rosas, SE Tao, K Xie, D Hamm, LL He, J AF Kelly, Tanika N. Raj, Dominic Rahman, Mahboob Kretzler, Matthias Kallem, Radhakrishna R. Ricardo, Ana C. Rosas, Sylvia E. Tao, Kaixiang Xie, Dawei Hamm, Lotuce Lee He, Jiang CA CRIC Study Investigators TI The role of renin-angiotensin-aldosterone system genes in the progression of chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE chronic kidney disease; genetics; renin-angiotensin-aldosterone system ID ACETYLCHOLINE-RECEPTOR GENES; BLOOD-PRESSURE; AMERICAN-INDIANS; FAMILY ANALYSIS; POLYMORPHISMS; ASSOCIATION; VARIANTS; RISK; ATHEROSCLEROSIS; DESIGN AB Background. We conducted single-marker, gene-and pathway-based analyses to examine the association between renin-angiotensin-aldosterone system (RAAS) variants and chronic kidney disease (CKD) progression among Chronic Renal Insufficiency Cohort study participants. Methods. A total of 1523 white and 1490 black subjects were genotyped for 490 single nucleotide polymorphisms (SNPs) in 12 RAAS genes as part of the ITMAT-Broad-CARe array. CKD progression phenotypes included decline in estimated glomerular filtration rate (eGFR) over time and the occurrence of a renal disease event, defined as incident end-stage renal disease or halving of eGFR from baseline. Mixed-effects models were used to examine SNP associations with eGFR decline, while Cox proportional hazards models tested SNP associations with renal events. Gene-and pathway-based analyses were conducted using the truncated product method. All analyses were stratified by race, and a Bonferroni correction was applied to adjust for multiple testing. Results. Among white and black participants, eGFR declined an average of 1.2 and 2.3 mL/min/1.73 m(2)/year, respectively, while renal events occurred in a respective 11.5 and 24.9% of participants. We identified strong gene-and pathway-based associations with CKD progression. The AGT and RENBP genes were consistently associated with risk of renal events in separate analyses of white and black participants (both P < 1.00 x 10(-6)). Driven by the significant gene-based findings, the entire RAAS pathway was also associated with renal events in both groups (both P < 1.00 x 10(-6)). No single-marker associations with CKD progression were observed. Conclusions. The current study provides strong evidence for a role of the RAAS in CKD progression. C1 [Kelly, Tanika N.; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA 70112 USA. [Raj, Dominic] George Washington Univ, Med Fac Associates, Washington, DC 20037 USA. [Rahman, Mahboob] Case Western Reserve Univ, Louis Stokes Cleveland VA Med Ctr, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Kretzler, Matthias] Univ Michigan, Ann Arbor, MI 48109 USA. [Kallem, Radhakrishna R.] Univ Penn, Translat Res Ctr, Philadelphia, PA 19104 USA. [Ricardo, Ana C.] Univ Illinois, Chicago, IL 60612 USA. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Boston, MA 02215 USA. [Tao, Kaixiang; Xie, Dawei] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hamm, Lotuce Lee; He, Jiang] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. RP Kelly, TN (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA 70112 USA. EM tkelly@tulane.edu FU NCATS NIH HHS [UL1 TR000424, UL1TR000439, UL1 TR000439, UL1 TR000433, UL1 TR000003, UL1 TR-000424, UL1TR000003, UL1TR000433]; NCRR NIH HHS [M01 RR-16500, UL1 RR029879, UL1 RR024131, M01 RR016500, UL1RR029879, UL1 RR-024131]; NIDDK NIH HHS [K23 DK094829, U01 DK060963, U01DK060902, U01 DK060984, R01 DK073665, U01 DK060902, R01 DK073665-01A1, U01DK060990, U01 DK061021, U01DK061028, U01DK060963, U01DK061022, U01DK060984, U01DK060980, U01 DK060990, U01 DK060980, U01DK061021, U01 DK061028, U01 DK061022]; NIGMS NIH HHS [P30GM103337, P30 GM103337] NR 36 TC 2 Z9 2 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD OCT PY 2015 VL 30 IS 10 BP 1711 EP 1718 DI 10.1093/ndt/gfv125 PG 9 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA CT9YG UT WOS:000363171900016 PM 25906781 ER PT J AU Huybrechts, KF Bateman, BT Palmsten, K Desai, RJ Patorno, E Gopalakrishnan, C Levin, R Mogun, H Hernandez-Diaz, S AF Huybrechts, Krista F. Bateman, Brian T. Palmsten, Kristin Desai, Rishi J. Patorno, Elisabetta Gopalakrishnan, Chandrasekar Levin, Raisa Mogun, Helen Hernandez-Diaz, Sonia TI Antidepressant Use Late in Pregnancy and Risk of Persistent Pulmonary Hypertension of the Newborn SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB The use of antidepressants during the third trimester of pregnancy has been implicated in the development of persistent pulmonary hypertension of the newborn (PPHN), which is known to cause substantial morbidity and mortality in infants. However, in 2011, the Food and Drug Administration noted that the findings on this issue were still premature, causing great controversy and concern. To address this issue, the authors of the present study examined whether antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs, increased the risk of PPHN development in infants. The authors evaluated the records of 128,950 women (12-55 years of age) who were exposed to an antidepressant, defined as filling 1 prescription of either an SSRI or a non-SSRI, during the 90 days before delivery of a live-born infant. Maternal and infant dataset records were extracted from the from the Medicaid Analytic eXtract database based on International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for persistent fetal circulation (747.83) or primary pulmonary hypertension (416.0x). Data were analyzed using both nonadjusted and adjusted logistic regression models, to account for different levels of confounding factors. A sensitivity analysis was also included, to account for potential exposure misclassification, wherein exposure was redefined as filling 2 prescriptions instead of 1. Infants exposed to antidepressants during the last 90 days of pregnancy, especially to SSRI antidepressants, were at statistically significantly higher risk for PPHN development when compared with unexposed infants (31.5 per 10,000 SSRI-exposed neonates, 29.1 per 10,000 non-SSRI-exposed neonates, and 20.8 per 10,000 unexposed infants). In the depression-restricted adjusted analysis, results showed that 33.8 SSRI-exposed, 34.4 non-SSRI-exposed, and 24.9 unexposed infants per 10,000 infants developed PPHN. For SSRI-exposed women, odds ratios were 1.51 (95% confidence interval [CI], 1.35-1.69; unadjusted) and 1.10 (95% CI, 0.94-1.29; depression diagnosis and propensity score adjusted). For non-SSRI-exposed women, odds ratios were 1.40 (95% CI, 1.12-1.75; unadjusted) and 1.02 (95% CI, 0.77-1.35; depression diagnosis and propensity score adjusted). No association was found between SSRI or non-SSRI antidepressants and severe PPHN. Sensitivity analysis did not yield significant differences between patients filling 1 prescription and patients filling 2 prescriptions. The results of this study support previous findings that there is potentially increased risk of PPHN associated with antidepressant use in late pregnancy. However, the authors found that after adjusting for depression and other confounding factors, the magnitude of risk is smaller than previously reported and was not statistically significant with either non-SSRI antidepressant use or SSRI antidepressant use. C1 [Huybrechts, Krista F.; Bateman, Brian T.; Desai, Rishi J.; Patorno, Elisabetta; Gopalakrishnan, Chandrasekar; Levin, Raisa; Mogun, Helen] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Huybrechts, Krista F.; Bateman, Brian T.; Patorno, Elisabetta] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.; Palmsten, Kristin] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA USA. RP Huybrechts, KF (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD OCT PY 2015 VL 70 IS 10 BP 607 EP 609 DI 10.1097/01.ogx.0000472158.66771.3e PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CU1WC UT WOS:000363311700004 ER PT J AU Butrick, M Kelly, S Peshkin, BN Luta, G Nusbaum, R Hooker, GW Graves, K Feeley, L Isaacs, C Valdimarsdottir, HB Jandorf, L DeMarco, T Wood, M McKinnon, W Garber, J McCormick, SR Schwartz, MD AF Butrick, Morgan Kelly, Scott Peshkin, Beth N. Luta, George Nusbaum, Rachel Hooker, Gillian W. Graves, Kristi Feeley, Lisa Isaacs, Claudine Valdimarsdottir, Heiddis B. Jandorf, Lina DeMarco, Tiffani Wood, Marie McKinnon, Wendy Garber, Judy McCormick, Shelley R. Schwartz, Marc D. TI Disparities in Uptake of BRCA1/2 Genetic Testing in a Randomized Trial of Telephone Counseling SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Genetic counseling via telephone (TC) has emerged as a potential avenue of care for women at risk of breast and ovarian cancers and open to BRCA1 and BRCA2 genetic testing. However, although TC has been shown to be on level with usual care (UC) methods in terms of knowledge, satisfaction, decisional quality, quality of life, and distress, all while yielding high cost savings to the patient and increasing patient accessibility, studies have also shown that patients randomized to TC are less like to complete the genetic testing process. In order to determine the factors leading to lower rates of genetic testing uptake after TC, the authors of this study examined sociodemographic, medical, and psychosocial predictors of genetic testing uptake and evaluated patient-related moderators (knowledge, numeracy, race/ethnicity, education level, etc) in a large cohort of women. In this noninferiority trial, 669 women (21-85 years old) seeking BRCA1/2 genetic testing, with no history of counseling or testing, were randomized into 2 groups, a TC group (n = 335) and an in-person counseling or UC group (n = 334). Measures included sociodemographics, medical history, intentions for risk-reducing surgery, perceived risk of BRCA mutation, perceived risk of breast and ovarian cancer, knowledge, numeracy, decisional conflict, cancer-specific distress, and quality of life. Analysis, logistic regression with backward elimination, was conducted within an intention-to-treat (ITT) sample, which included all randomized participants regardless of genetic counseling session completion, and with a per-protocol (PP) sample, limited to participants who completed genetic counseling as assigned. Within both the ITT and PP samples, genetic testing uptake was lower in the TC group than in the UC group (ITT: 74.9% vs 81.4%, P = 0.04; PP: 84.2% vs 90.1%, P = 0.03). In the ITT population, independently associated significant predictors of completing genetic testing were non-Hispanic white race/ethnicity (odds ratio [OR], 1.96; P = 0.007), randomization to UC (OR, 1.48; P = 0.045), higher knowledge (OR, 1.12; P = 0.018), and lower perceived stress (OR, 0.89; P = 0.017). In the PP sample, independently associated predictors were marital status (OR, 1.85; P = 0.017), objective mutation risk (OR, 1.22; P = 0.007), knowledge (OR, 1.13; P = 0.050), and randomization to UC (OR, 1.65; P =0.050). Considering both ITT and PP analyses, it is of note that knowledge, perceived stress, and objective risk did not interact with group assignment in either analysis (marital status was not tested). In regard to potential moderator variables, the only variable that reached statistical and clinical significance in both samples was race/ethnicity (ITT: P =0.054; PP: P = 0.028). Overall, the strongest moderator affecting genetic testing uptake after TC was race/ethnicity. When randomized to TC, minority women were less likely to complete BRCA1/2 genetic testing. Despite these lower rates, which may be due in part to practical barriers (unlike UC patients, TC patients need to travel to an alternate location to provide a DNA sample), this finding needs to be balanced with the possibility that TC may increase access in the first place. Further studies on availability of TC and its effect on overall rates should be conducted as other modes of delivery emerge for genetic counseling and testing. C1 [Butrick, Morgan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Kelly, Scott; Peshkin, Beth N.; Nusbaum, Rachel; Graves, Kristi; Feeley, Lisa; Isaacs, Claudine; DeMarco, Tiffani; Schwartz, Marc D.] Georgetown Univ, Dept Oncol, Canc Prevent & Control Program, Washington, DC USA. [Kelly, Scott; Peshkin, Beth N.; Nusbaum, Rachel; Graves, Kristi; Feeley, Lisa; Isaacs, Claudine; DeMarco, Tiffani; Schwartz, Marc D.] Georgetown Univ, Fisher Ctr Familial Canc Res, Washington, DC USA. [Luta, George] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC USA. [Hooker, Gillian W.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Valdimarsdottir, Heiddis B.; Jandorf, Lina] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA. [Wood, Marie; McKinnon, Wendy] Univ Vermont, Coll Med, Vermont Canc Ctr, Familial Canc Program, Burlington, VT USA. [Garber, Judy; McCormick, Shelley R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genet & Prevent, Boston, MA 02115 USA. RP Butrick, M (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD OCT PY 2015 VL 70 IS 10 BP 614 EP 616 DI 10.1097/01.ogx.0000472122.98775.a5 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CU1WC UT WOS:000363311700008 ER PT J AU Kothari, S Foster, CS Pistilli, M Liesegang, TL Daniel, E Sen, HN Suhler, EB Thorne, JE Jabs, DA Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Lawrence, SD Kempen, JH AF Kothari, Srishti Foster, C. Stephen Pistilli, Maxwell Liesegang, Teresa L. Daniel, Ebenezer Sen, H. Nida Suhler, Eric B. Thorne, Jennifer E. Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Lawrence, Scott D. Kempen, John H. CA Systemic Immunosuppressive Therapy TI The Risk of Intraocular Pressure Elevation in Pediatric Noninfectious Uveitis SO OPHTHALMOLOGY LA English DT Article ID SECONDARY GLAUCOMA; REGRESSION-ANALYSIS; STANDARDIZATION; PATHOGENESIS; DISEASE; DEXAMETHASONE; NOMENCLATURE; CHILDHOOD; CHILDREN; STEROIDS AB Purpose: To characterize the risk and risk factors for intraocular pressure (IOP) elevation in pediatric noninfectious uveitis. Design: Multicenter retrospective cohort study. Participants: Nine hundred sixteen children (1593 eyes) younger than 18 years at presentation with noninfectious uveitis followed up between January 1978 and December 2007 at 5 academic uveitis centers in the United States. Methods: Medical records review by trained, certified experts. Main Outcome Measures: Prevalence and incidence of IOP of 21 mmHg or more and 30 mmHg or more and incidence of a rise in IOP by 10 mmHg or more. To avoid underascertainment, outcomes were counted as present when IOP-lowering therapies were in use. Results: Initially, 251 (15.8%) and 46 eyes (2.9%) had IOP >= 21 mmHg and >= 30 mmHg, respectively. Factors significantly associated with presenting IOP elevation included age of 6 to 12 years (versus other pediatric ages), prior cataract surgery, pars plana vitrectomy, duration of uveitis >= 6 months, contralateral IOP elevation, presenting visual acuity worse than 20/40, and topical corticosteroid use (in a dose-response relationship). The median follow-up was 1.25 years (interquartile range, 0.4-3.66). The estimated incidence of any observed IOP elevation to >= 21 mmHg, to >= 30 mmHg, and increase in IOP by >= 10 mmHg was 33.4%, 14.8%, and 24.4%, respectively, within 2 years. Factors associated with IOP elevation included pars plana vitrectomy, contralateral IOP elevation (adjusted hazard ratio [aHR], up to 9.54; P < 0.001), and the use of topical (aHR, up to 8.77 that followed a dose-response relationship; P < 0.001), periocular (aHR, up to 7.96; P < 0.001), and intraocular (aHR, up to 19.7; P < 0.001) corticosteroids. Conclusions: Intraocular pressure elevation affects a large minority of children with noninfectious uveitis. Statistically significant risk factors include IOP elevation or use of IOP-lowering treatment in the contralateral eye and local corticosteroid use that demonstrated a dose-and route of administration-dependent relationship. In contrast, use of immunosuppressive drug therapy did not increase such risk. Pediatric eyes with noninfectious uveitis should be followed up closely for IOP elevation, especially when strong risk factors such as the use of local corticosteroids and contralateral IOP elevation are present. (C) 2015 by the American Academy of Ophthalmology. C1 [Kothari, Srishti; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Waltham, MA USA. [Kothari, Srishti; Foster, C. Stephen] Ocular Immunol & Uveitis Fdn, Waltham, MA USA. [Kothari, Srishti; Pistilli, Maxwell; Daniel, Ebenezer; Kempen, John H.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Pistilli, Maxwell; Kempen, John H.] Univ Penn, Ctr Prevent Ophthalmol & Biostat, Scheie Eye Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Liesegang, Teresa L.; Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Levy-Clarke, Grace A.] Tampa Bay Uveitis Ctr, Safety Harbor, FL USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Rosenbaum, James T.] Devers Eye Inst, Portland, OR USA. [Lawrence, Scott D.] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA. [Kempen, John H.] Univ Penn, Ctr Prevent Ophthalmol & Biostat, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Kempen, JH (reprint author), Univ Penn, Ctr Prevent Ophthalmol & Biostat, Dept Ophthalmol, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu FU National Eye Institute; National Eye Institute, National Institutes of Health, Bethesda, Maryland [EY014943]; Research to Prevent Blindness, Inc., New York, New York; Paul and Evanina Mackall Foundation; Lois Pope Life Foundation (New York, NY); Research to Prevent Blindness James S. Adams Special Scholar Award; Research to Prevent Blindness Harrington Special Scholar Award; Research to Prevent Blindness Senior Scientific Investigator Award; Department of Veterans' Affairs, Washington, DC FX Supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant no.: EY014943 [J.H.K.]); Research to Prevent Blindness, Inc., New York, New York; the Paul and Evanina Mackall Foundation; the Lois Pope Life Foundation (New York, NY); J.H.K. was a Research to Prevent Blindness James S. Adams Special Scholar Award recipient; J.E.T. was a Research to Prevent Blindness Harrington Special Scholar Award recipient; and D.A.J. and J.T.R. were Research to Prevent Blindness Senior Scientific Investigator Award recipients during the course of the study; G.A.L.-C. previously was supported by and R.B.N. and H.N.S. continue to be supported by intramural funds from the National Eye Institute; E.B.S. receives support from the Department of Veterans' Affairs, Washington, DC. None of the sponsors had any role in the design and conduct of the report; collection, management, analysis, and interpretation of the data; or in the preparation, review, and approval of this manuscript. NR 44 TC 3 Z9 3 U1 1 U2 1 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 OCT PY 2015 VL 122 IS 10 BP 1987 EP 2001 DI 10.1016/j.ophtha.2015.06.041 PG 15 WC Ophthalmology SC Ophthalmology GA CU4IP UT WOS:000363491500015 PM 26233626 ER PT J AU Saadatpour, A Lai, SJ Guo, GJ Yuan, GC AF Saadatpour, Assieh Lai, Shujing Guo, Guoji Yuan, Guo-Cheng TI Single-Cell Analysis in Cancer Genomics SO TRENDS IN GENETICS LA English DT Review ID GENE-EXPRESSION ANALYSIS; CIRCULATING TUMOR-CELLS; EMBRYONIC STEM-CELLS; MESSENGER-RNA-SEQ; MASS CYTOMETRY; TRANSCRIPTOME ANALYSIS; NETWORK ANALYSIS; FATE DECISIONS; IN-SITU; T-SNE AB Genetic changes and environmental differences result in cellular heterogeneity among cancer cells within the same tumor, thereby complicating treatment outcomes. Recent advances in single-cell technologies have opened new avenues to characterize the intra-tumor cellular heterogeneity, identify rare cell types, measure mutation rates, and, ultimately, guide diagnosis and treatment. In this paper we review the recent single-cell technological and computational advances at the genomic, transcriptomic, and proteomic levels, and discuss their applications in cancer research. C1 [Saadatpour, Assieh; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Saadatpour, Assieh; Yuan, Guo-Cheng] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lai, Shujing; Guo, Guoji] Zhejiang Univ, Sch Med, Ctr Stem Cell & Regenerat Med, Hangzhou 310058, Zhejiang, Peoples R China. [Yuan, Guo-Cheng] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Guo, GJ (reprint author), Zhejiang Univ, Sch Med, Ctr Stem Cell & Regenerat Med, Hangzhou 310058, Zhejiang, Peoples R China. EM ggj@zju.edu.cn; gcyuan@jimmy.harvard.edu FU Claudia Adams Barr Award FX This work was supported in part by a Claudia Adams Barr Award to G-C.Y. NR 99 TC 16 Z9 16 U1 7 U2 51 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 2015 VL 31 IS 10 SI SI BP 576 EP 586 DI 10.1016/j.tig.2015.07.003 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA CU2JN UT WOS:000363349900005 PM 26450340 ER PT J AU Ordovas-Montanes, J Rakoff-Nahoum, S Huang, SY Riol-Blanco, L Barreiro, O von Andrian, UH AF Ordovas-Montanes, Jose Rakoff-Nahoum, Seth Huang, Siyi Riol-Blanco, Lorena Barreiro, Olga von Andrian, Ulrich H. TI The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease SO TRENDS IN IMMUNOLOGY LA English DT Review ID ALLERGIC AIRWAY INFLAMMATION; INNATE LYMPHOID-CELLS; VASOACTIVE-INTESTINAL-PEPTIDE; A-INDUCED BRONCHOCONSTRICTION; HEMATOPOIETIC STEM-CELLS; CUTANEOUS SENSORY NERVES; HERPES-SIMPLEX-VIRUS; GENE-RELATED PEPTIDE; BONE-MARROW NICHE; NERVOUS-SYSTEM AB The nervous system and the immune system are the principal sensory interfaces between the internal and external environment. They are responsible for recognizing, integrating, and responding to varied stimuli, and have the capacity to form memories of these encounters leading to learned or 'adaptive' future responses. We review current understanding of the cross-regulation between these systems. The autonomic and somatosensory nervous systems regulate both the development and deployment of immune cells, with broad functions that impact on hematopoiesis as well as on priming, migration, and cytokine production. In turn, specific immune cell subsets contribute to homeostatic neural circuits such as those controlling metabolism, hypertension, and the inflammatory reflex. We examine the contribution of the somatosensory system to autoimmune, autoinflammatory, allergic, and infectious processes in barrier tissues and, in this context, discuss opportunities for therapeutic manipulation of neuro-immune interactions. C1 [Ordovas-Montanes, Jose; Rakoff-Nahoum, Seth; Huang, Siyi; Barreiro, Olga; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & lmmunobiol, Boston, MA 02115 USA. [Rakoff-Nahoum, Seth] Boston Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Rakoff-Nahoum, Seth] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Riol-Blanco, Lorena] Genentech Inc, Dept Immunobiol, San Francisco, CA 94080 USA. [von Andrian, Ulrich H.] MIT, Ragon Inst, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. [von Andrian, Ulrich H.] Harvard Univ, Cambridge, MA 02139 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Dept Microbiol & lmmunobiol, Boston, MA 02115 USA. EM uva@hms.harvard.edu FU Ragon Institute of MGH; National Institutes of Health [AR068383, AI112521, AI069259, AI111595, AI095261, AR063546]; PIDS-St Jude Research Hospital Fellowship Program in Basic Research; Harvard University; MIT FX The authors wish to thank Ms E. Nigro for secretarial support and Dr G. Cheng and L. Jones for technical assistance. This work was supported by funds from the Ragon Institute of MGH, MIT, and Harvard University, and by National Institutes of Health grants AR068383, AI112521, AI069259, AI111595 and AI095261 (to U.H.v.A) and AR063546 (to J.O-M.) and by the PIDS-St Jude Research Hospital Fellowship Program in Basic Research (to SR-N.), NR 247 TC 13 Z9 13 U1 0 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 EI 1471-4981 J9 TRENDS IMMUNOL JI Trends Immunol. PD OCT PY 2015 VL 36 IS 10 BP 578 EP 604 DI 10.1016/j.it.2015.08.007 PG 27 WC Immunology SC Immunology GA CT8MI UT WOS:000363070300004 PM 26431937 ER PT J AU Chatterjee, P Tsai, TC Jha, AK AF Chatterjee, Paula Tsai, Thomas C. Jha, Ashish K. TI Delivering Value by Focusing on Patient Experience SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CARE; SATISFACTION; QUALITY AB The use of patient experience as a quality metric in healthcare remains controversial. Clinicians have expressed concern that incentives focused on patient experience may lead to lower quality care. However, empirical evidence from the United States and abroad suggests that hospitals and ambulatory care providers with higher patient satisfaction scores also perform better on clinical process and outcome measures. While it may be that high-performing providers simply have more resources to devote to both patient experience and the technical aspects of care, we suspect that these providers' performance is also driven by a conscious commitment to quality. As the country shifts toward new payment models, we should encourage this type of commitment to quality. Perhaps most importantly, improving the patient experience will build trust in the healthcare system, guard against withholding of services in the face of changing provider incentives, and promote collaboration between clinicians and patients. Therefore, patient experience measures should play a critical role in how we judge high-quality, value-based care. C1 [Chatterjee, Paula; Jha, Ashish K.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Tsai, Thomas C.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Tsai, Thomas C.; Jha, Ashish K.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Jha, AK (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu NR 8 TC 4 Z9 4 U1 1 U2 6 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD OCT PY 2015 VL 21 IS 10 BP 735 EP 737 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CT6VI UT WOS:000362950100007 PM 26633097 ER PT J AU D'Avanzo, C Aronson, J Kim, YH Choi, SH Tanzi, RE Kim, DY AF D'Avanzo, Carla Aronson, Jenna Kim, Young Hye Choi, Se Hoon Tanzi, Rudolph E. Kim, Doo Yeon TI Alzheimer's in 3D culture: Challenges and perspectives SO BIOESSAYS LA English DT Article DE 3D culture; Alzheimer's disease; APP; human stem cell; presenelin ID AMYLOID-PRECURSOR-PROTEIN; TRANSGENIC MOUSE MODEL; GAMMA-SECRETASE ACTIVITY; PLURIPOTENT STEM-CELLS; INTRACELLULAR A-BETA; IPSC-DERIVED NEURONS; PLAQUE-FORMATION; DISEASE; MICE; APP AB Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The beta-amyloid cascade hypothesis of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including beta-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. C1 [D'Avanzo, Carla; Aronson, Jenna; Choi, Se Hoon; Tanzi, Rudolph E.; Kim, Doo Yeon] Harvard Univ, Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis,Med Sch, Charlestown, MA 02129 USA. [Kim, Young Hye] Korea Basic Sci Inst, Biomed Om Grp, Cheongju, Chungbuk, South Korea. RP Kim, DY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis,Med Sch, Charlestown, MA 02129 USA. EM dkim@helix.mgh.harvard.edu FU Cure Alzheimer's fund; Bio & Medical Technology Development Program of the National Research Foundation - Korean government, MSIP [2015M3A9C7030151]; National Institute of Health [1RF1AG048080-01, 5P01AG15379, 2R01AG014713, 5R37MH060009] FX This work is supported by the grants from the Cure Alzheimer's fund to D.Y.K., S.H.C., and R.E.T., the Bio & Medical Technology Development Program of the National Research Foundation funded by the Korean government, MSIP (2015M3A9C7030151, Y.H.K), and National Institute of Health (1RF1AG048080-01, D.Y.K. and R.E.T.; 5P01AG15379, D.Y.K. and R.E.T.; 2R01AG014713, D.Y.K.; 5R37MH060009, R.E.T.). We appreciate Drs. Sang Su Kwak and Raja Bhattacharyya for the critical reading and helpful suggestions. C.D. and J.A. were equally responsible for designing, writing and preparing the manuscript. S.H.C., Y.H.K., and D.Y.K. contributed to the writing and R.E.T. and D.Y.K supervised and finalized the manuscript. NR 72 TC 5 Z9 5 U1 9 U2 27 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 OCT PY 2015 VL 37 IS 10 BP 1139 EP 1148 DI 10.1002/bies.201500063 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CT3UE UT WOS:000362731600013 PM 26252541 ER PT J AU Michaelson, MD McKay, RR Werner, L Atkins, MB Van Allen, EM Olivier, KM Song, JX Signoretti, S McDermott, DF Choueiri, TK AF Michaelson, M. Dror McKay, Rana R. Werner, Lillian Atkins, Michael B. Van Allen, Eliezer M. Olivier, Kara M. Song, Jiaxi Signoretti, Sabina McDermott, David F. Choueiri, Toni K. TI Phase 2 Trial of Sunitinib and Gemcitabine in Patients With Sarcomatoid and/or Poor-Risk Metastatic Renal Cell Carcinoma SO CANCER LA English DT Article DE chemotherapy; poor risk; renal cell carcinoma; sarcomatoid; vascular endothelial growth factor (VEGF); targeted ID INTERFERON-ALPHA; III TRIAL; CHEMOTHERAPY; BEVACIZUMAB; COMBINATION; CANCER; DIFFERENTIATION; CAPECITABINE; INHIBITORS; REGIMEN AB BACKGROUND: Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC. METHODS: This was a phase 2, single-arm trial of sunitinib and gemcitabine in patients with sarcomatoid or poor-risk RCC. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the time to progression (TTP), overall survival (OS), safety, and biomarker correlatives. RESULTS: Overall, 39 patients had sarcomatoid RCC, and 33 had poor-risk RCC. The ORR was 26% for patients with sarcomatoid RCC and 24% for patients with poor-risk RCC. The median TTP and OS for patients with sarcomatoid RCC were 5 and 10 months, respectively. For patients with poor-risk disease, the median TTP and OS were 5.5 and 15 months, respectively. Patients whose tumors had >10% sarcomatoid histology had a higher clinical benefit rate (ORR plus stable disease) than those with <= 10% sarcomatoid histology (P=.04). The most common grade 3 or higher treatment-related adverse events included neutropenia (n = 20), anemia (n = 10), and fatigue (n = 7). CONCLUSIONS: These results suggest that antiangiogenic therapy and cytotoxic chemotherapy are an active and well-tolerated combination for patients with aggressive RCC. The combination may be more efficacious than either therapy alone and is currently under further investigation. (C) 2015 American Cancer Society. C1 [Michaelson, M. Dror; Olivier, Kara M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [McKay, Rana R.; Van Allen, Eliezer M.; Choueiri, Toni K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Kidney Canc Ctr, Boston, MA 02115 USA. [Werner, Lillian] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Dept Med Oncol, Washington, DC USA. [Song, Jiaxi; Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Ctr Canc, Claire & John Bertucci Ctr Genitourinary Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM dmichaelson1@partners.org OI Michaelson, Dror/0000-0001-9249-6338 FU Pfizer; Dana-Farber/Harvard Cancer Center Kidney Specialized Program of Research Excellence [P50CA101942]; Trust Family; Loker Pinard Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute FX This study was sponsored by Pfizer. In addition, this research was funded in part by the Dana-Farber/Harvard Cancer Center Kidney Specialized Program of Research Excellence (P50CA101942) and by the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute (to Toni K. Choueiri). NR 28 TC 9 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2015 VL 121 IS 19 BP 3435 EP 3443 DI 10.1002/cncr.29503 PG 9 WC Oncology SC Oncology GA CT4MY UT WOS:000362782000015 PM 26058385 ER PT J AU Dupuy, DE Fernando, HC Hillman, S Ng, T Tan, AD Sharma, A Rilling, WS Hong, K Putnam, JB AF Dupuy, Damian E. Fernando, Hiran C. Hillman, Shauna Ng, Thomas Tan, Angelina D. Sharma, Amita Rilling, William S. Hong, Kelvin Putnam, Joe B. TI Radiofrequency Ablation of Stage IA Non-Small Cell Lung Cancer in Medically Inoperable Patients: Results From the American College of Surgeons Oncology Group Z4033 (Alliance) Trial SO CANCER LA English DT Article DE ablation; elderly; non-small cell lung cancer (NSCLC); radiofrequency ablation (RFA); stereotactic body radiotherapy (SBRT) ID BODY RADIATION-THERAPY; INTENTION-TO-TREAT; THERMAL ABLATION; SUBLOBAR RESECTION; MALIGNANCIES; RADIOTHERAPY AB BACKGROUND: This study evaluated the 2-year overall survival rate, adverse event rate, local control rate, and impact on pulmonary function tests for medically inoperable patients with stage IA non-small cell lung cancer (NSCLC) undergoing computed tomography (CT)-guided radiofrequency ablation (RFA) in a prospective, multicenter trial. METHODS: Fifty-four patients (25 men and 29 women) with a median age of 76 years (range, 60-89 years) were enrolled from 16 US centers; 51 patients were eligible for evaluation (they had biopsy-proven stage IA NSCLC and were deemed medically inoperable by a board-certified thoracic surgeon). Pulmonary function tests were performed within the 60 days before RFA and 3 and 24 months after RFA. Adverse events were recorded and categorized. Patients were followed with CT and fludeoxyglucose positron emission tomography. Local control rate and recurrence patterns were analyzed. RESULTS: The overall survival rate was 86.3% at 1 year and 69.8% at 2 years. The local tumor recurrence-free rate was 68.9% at 1 year and 59.8% at 2 years and was worse for tumors> 2 cm. In the 19 patients with local recurrence, 11 were re-treated with RFA, 9 underwent radiation, and 3 underwent chemotherapy. There were 21 grade 3 adverse events, 2 grade 4 adverse events, and 1 grade 5 adverse event in 12 patients within the first 90 days after RFA. None of the grade 4 or 5 adverse events were attributable to RFA. There was no significant change in the forced expiratory volume in the first second of expiration or the diffusing capacity of lung for carbon monoxide after RFA. A tumor size less than 2.0 cm and a performance status of 0 or 1 were associated with statistically significant improved survival of 83% and 78%, respectively, at 2 years. CONCLUSIONS: RFA is a single, minimally invasive procedure that is well tolerated in medically inoperable patients, does not adversely affect pulmonary function tests, and provides a 2-year overall survival rate that is comparable to the rate reported after stereotactic body radiotherapy in similar patients. (C) 2015 American Cancer Society. C1 [Dupuy, Damian E.; Ng, Thomas] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence, RI 02903 USA. [Fernando, Hiran C.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [Hillman, Shauna; Tan, Angelina D.] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA. [Sharma, Amita] Massachusetts Gen Hosp, Radiol Associates, Boston, MA 02114 USA. [Rilling, William S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Hong, Kelvin] Johns Hopkins Univ Hosp, Johns Hopkins Med Ctr, Baltimore, MD 21287 USA. [Putnam, Joe B.] Vanderbilt Univ, Med Ctr, Vanderbilt Clin, Nashville, TN USA. RP Dupuy, DE (reprint author), Brown Univ, Rhode Isl Hosp, Alpert Med Sch, 593 Eddy St, Providence, RI 02903 USA. EM ddupuy@lifespan.org OI Dupuy, Damian/0000-0003-0524-5982 FU National Institutes of Health [U10 CA 76001]; Valleylab (Covidien) Boulder, CO FX This study was supported by the National Institutes of Health (grant U10 CA 76001) and Valleylab (Covidien) Boulder, CO. NR 23 TC 19 Z9 21 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2015 VL 121 IS 19 BP 3491 EP 3498 DI 10.1002/cncr.29507 PG 8 WC Oncology SC Oncology GA CT4MY UT WOS:000362782000022 PM 26096694 ER PT J AU Paulson, EC Veenstra, CM Vachani, A Ciunci, CA Epstein, AJ AF Paulson, E. Carter Veenstra, Christine M. Vachani, Anil Ciunci, Christine A. Epstein, Andrew J. TI Trends in Surveillance for Resected Colorectal Cancer, 2001-2009 SO CANCER LA English DT Article DE colon cancer; epidemiology; guideline adherence; rectal cancer; surveillance ID FOLLOW-UP; PRACTICE GUIDELINE; AMERICAN-SOCIETY; COLON-CANCER; SURVIVORS; POPULATION; PROTOCOL; RECEIPT; CARE AB BACKGROUND: Little is known about recent trends in surveillance among the more than 1 million US colorectal cancer (CRC) survivors. Moreover, for stage I disease, which accounts for more than 30% of survivors, the guidelines are limited, and the use of surveillance has not been well studied. Guidelines were changed in 2005 to include recommendations for computed tomography (CT) surveillance in select patients, but the impact of these changes has not been explored. METHODS: A retrospective analysis of patients who were identified in the Survival, Epidemiology, and End Results-Medicare database and underwent resection of stage I to III CRC between 2001 and 2009 was performed. The receipt of guideline-determined sufficient surveillance, including office visits, colonoscopy, carcinoembryonic antigen (CEA) testing, and CT imaging, in the 3 years after resection was evaluated. RESULTS: The study included 23,990 colon cancer patients and 5665 rectal cancer patients. Rates of office visits and colonoscopy were high and stable over the study period. Rates of CEA surveillance increased over the study period but remained low, even for stage III disease. Rates of CT imaging increased gradually during the study period, but the 2005 guideline change had no effect. Stage II patients, including high-risk patients, received surveillance at significantly lower rates than stage III patients despite similar recommendations. Conversely, up to 30% of stage I patients received nonrecommended CEA testing and CT imaging. CONCLUSIONS: There continues to be substantial underuse of surveillance for CRC survivors and particularly for stage II patients, who constitute almost 40% of survivors. The 2005 guideline change had a negligible impact on CT surveillance. Conversely, although guidelines are limited, many stage I patients are receiving intensive surveillance. (C) 2015 American Cancer Society. C1 [Paulson, E. Carter; Vachani, Anil; Ciunci, Christine A.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Paulson, E. Carter; Epstein, Andrew J.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Paulson, E. Carter; Epstein, Andrew J.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Veenstra, Christine M.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Veenstra, Christine M.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Epstein, Andrew J.] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Paulson, EC (reprint author), Philadelphia VA Med Ctr, Surg Business Off, 3900 Woodland Ave,5th Floor, Philadelphia, PA 19104 USA. EM paulsone@uphs.upenn.edu FU National Cancer Institute (Cancer Center Support) [P30 CA016520]; Abramson Cancer Center Population Science Pilot Project FX This study was supported by the National Cancer Institute (Cancer Center Support Grant P30 CA016520) and the Abramson Cancer Center Population Science Pilot Project. NR 18 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2015 VL 121 IS 19 BP 3525 EP 3533 DI 10.1002/cncr.29469 PG 9 WC Oncology SC Oncology GA CT4MY UT WOS:000362782000026 PM 26079928 ER PT J AU Moore, CW Rauch, PK Baer, L Pirl, WF Muriel, AC AF Moore, Cynthia W. Rauch, Paula K. Baer, Lee Pirl, William F. Muriel, Anna C. TI Parenting Changes in Adults With Cancer SO CANCER LA English DT Article DE cancer; depression; family relations; parenting; quality of life; self-efficacy ID ENHANCING CONNECTIONS PROGRAM; BREAST-CANCER; FUNCTIONAL ASSESSMENT; PSYCHOLOGIC DISTRESS; CHILDREN; FAMILY; DEPRESSION; POPULATION; ADJUSTMENT; PREDICTORS AB BACKGROUND: Children whose parents have cancer are at risk for psychosocial difficulties; however, the mechanisms are not well understood. This cross-sectional study sought support for a model connecting parental cancer to child distress through its impact on parenting self-efficacy beliefs and parenting behaviors by examining relations among parental illness, quality of life/parent functioning, parenting efficacy beliefs, and concerns about children's emotional distress. METHODS: One hundred ninety-four adult oncology outpatients with children who were 18 years old or younger completed questionnaires assessing their health-related quality of life (Functional Assessment of Cancer Therapy-General), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), overall distress (Distress Thermometer), and parenting efficacy beliefs and parenting concerns (Parenting Concerns Questionnaire). RESULTS: Parenting efficacy scores for parents and coparents declined significantly after diagnosis. This decline correlated with more visits to a medical clinic, treatment with intravenous chemotherapy in the past month, poorer health-related quality of life, and more depression and distress. Parents experiencing the most concern about the impact of mood, physical limitations, and changes in routines on their children experienced the biggest declines in their own sense of efficacy as parents and in their belief in their coparent's efficacy. Finally, declines in parenting efficacy beliefs correlated with parental concerns about children's emotional distress about aspects of the parent's illness. CONCLUSIONS: This study highlights the importance of identifying and addressing parenting concerns to alleviate patient distress, and it may help to guide future intervention efforts. (C) 2015 American Cancer Society. C1 [Moore, Cynthia W.; Rauch, Paula K.; Baer, Lee; Pirl, William F.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Muriel, Anna C.] Dana Farber Canc Inst, Div Pediat Psychosocial Oncol, Boston, MA 02115 USA. RP Moore, CW (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 6900, Boston, MA 02115 USA. EM cmoore8@partners.org FU National Institutes of Health [R03 CA126394-01] FX This research was supported by the National Institutes of Health (grant R03 CA126394-01). NR 23 TC 3 Z9 3 U1 4 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2015 VL 121 IS 19 BP 3551 EP 3557 DI 10.1002/cncr.29525 PG 7 WC Oncology SC Oncology GA CT4MY UT WOS:000362782000029 PM 26094587 ER PT J AU Kuruppu, D Tanabe, KK AF Kuruppu, D. Tanabe, K. K. TI HSV-1 as a novel therapy for breast cancer meningeal metastases SO CANCER GENE THERAPY LA English DT Article ID VIRAL ONCOLYSIS; LEPTOMENINGEAL METASTASIS; VIRUS; PET AB Meningeal metastasis is a fatal complication of breast cancer that affects 5-8% of patients. When cancer cells seed in the meninges, their subsequent growth results in severe neurological complications involving the cranial nerves, cerebrum and spinal cord, limiting life expectancy to less than 4 months. The incidences of meningeal metastases increase with prolonged lifespan resulting from treatment advances for primary breast cancer and their metastases. Currently, there is no cure. Aggressive multimodal therapies such as radiation and chemotherapy (intra-cerebrospinal fluid (CSF) and systemic) are ineffective. Therapeutic agents are often quickly cleared from the CSF, while higher doses that can achieve a therapeutic response are highly toxic. The secure guarding of the subarachnoid space by the blood-brain barrier on one side and the blood-CSF barrier on the other prevents chemotherapy from reaching cancer cells in the meninges. These challenges with treating meningeal metastases highlight the urgent need for a new therapeutic modality. An ideal treatment would be an agent that avoids rapid clearance, remains within the CSF, reaches the meninges and selectively destroys tumor cells. Replication conditional oncolytic herpes simplex virus type 1 (HSV-1) may be effective in this regard. Viral oncolysis, the destruction of cancer cells by replicating virus, is under clinical investigation for cancers that are unresponsive to current therapies. It is based on the model of multiple cycles of lytic virus replication in cancer cells that amplify the injected dose. The therapeutic potential of oncolytic HSV-1 for breast cancer meningeal metastases is discussed here. HSV-1 could be a potential novel treatment for meningeal metastases that can be translated to the clinic. C1 [Kuruppu, D.; Tanabe, K. K.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Kuruppu, D (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren 401,55 Fruit St, Boston, MA 02114 USA. EM dkuruppu@partners.org FU NCI NIH HHS [R21 CA186054] NR 10 TC 3 Z9 3 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 EI 1476-5500 J9 CANCER GENE THER JI Cancer Gene Ther. PD OCT PY 2015 VL 22 IS 10 BP 506 EP 508 DI 10.1038/cgt.2015.43 PG 3 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA CT6GS UT WOS:000362912100006 PM 26384139 ER PT J AU Velasquez, GE Aibana, O Ling, EJ Diakite, I Mooring, EQ Murray, MB AF Velasquez, Gustavo E. Aibana, Omowunmi Ling, Emilia J. Diakite, Ibrahim Mooring, Eric Q. Murray, Megan B. TI Time From Infection to Disease and Infectiousness for Ebola Virus Disease, a Systematic Review SO CLINICAL INFECTIOUS DISEASES LA English DT Review DE Ebola; incubation period; latent period; transmission; systematic review ID HEMORRHAGIC-FEVER; CLINICAL-OBSERVATIONS; WEST-AFRICA; DYNAMICS; ZAIRE; TRANSMISSION; OUTBREAK; CONGO; SUDAN AB We systematically reviewed the literature to estimate the incubation and latent periods of Ebola virus disease. We found limited epidemiological data from individuals with discrete 1-day exposures. Available data suggest that the incubation and latent periods may differ, and mathematical models may be improved by distinguishing between the two periods. C1 [Velasquez, Gustavo E.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Aibana, Omowunmi] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Velasquez, Gustavo E.; Murray, Megan B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Aibana, Omowunmi] Miriam Hosp, Div Infect Dis, Providence, RI 02906 USA. [Ling, Emilia J.; Mooring, Eric Q.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Mooring, Eric Q.] Harvard Univ, TH Chan Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA USA. [Diakite, Ibrahim; Murray, Megan B.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. RP Velasquez, GE (reprint author), Brigham & Womens Hosp, Div Infect Dis, 15 Francis St,PBB-A4, Boston, MA 02115 USA. EM gvelasqu@post.harvard.edu OI Velasquez, Gustavo/0000-0003-1438-0692 FU NIAID [T32 AI007433]; National Institute on Drug Abuse [T32 DA013911]; National Institute of General Medical Sciences at NIH [U54 GM088558] FX This work was supported by the NIAID [T32 AI007433 to G. E. V.]; the National Institute on Drug Abuse [T32 DA013911 to O. A.]; and the National Institute of General Medical Sciences [U54 GM088558 to E. Q. M.] at the NIH. NR 28 TC 3 Z9 3 U1 2 U2 27 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2015 VL 61 IS 7 BP 1135 EP 1140 DI 10.1093/cid/civ531 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6VZ UT WOS:000362952100017 PM 26129757 ER PT J AU Walensky, RP Hirsch, MS AF Walensky, Rochelle P. Hirsch, Martin S. TI Age-Old Questions: When to Start Antiretroviral Therapy and in Whom? SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE HIV; aging; when to start ART; CD4 ID HIV-INFECTION; INITIATION C1 [Walensky, Rochelle P.; Hirsch, Martin S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, 65 Landsdowne St,Rm 419, Cambridge, MA 02139 USA. EM mshirsch@partners.org NR 17 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2015 VL 61 IS 7 BP 1196 EP 1198 DI 10.1093/cid/civ467 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6VZ UT WOS:000362952100028 PM 26082510 ER PT J AU Tereshchenko, LG Waks, JW Kabir, M Ghafoori, E Shvilkin, A Josephson, ME AF Tereshchenko, Larisa G. Waks, Jonathan W. Kabir, Muammar Ghafoori, Elyar Shvilkin, Alexei Josephson, Mark E. TI Analysis of speed, curvature, planarity and frequency characteristics of heart vector movement to evaluate the electrophysiological substrate associated with ventricular tachycardia SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE Ventricular tachycardia; Heart vector; Conduction velocity; Vectorcardiography; Speed; Curvature; Planarity; Frequency characteristics ID VECTORCARDIOGRAPHIC LOOP ALIGNMENT; CARDIAC-RHYTHM ABNORMALITIES; CORONARY-ARTERY-DISEASE; TO-BEAT VARIABILITY; DEFIBRILLATOR IMPLANTATION; CATHETER ABLATION; PREDICTIVE-VALUE; 2008 GUIDELINES; THERAPY; ELECTROCARDIOGRAM AB Background: We developed a novel method of assessing ventricular conduction using the surface ECG. Methods: Orthogonal ECGs of 81 healthy controls (age 39.0 +/- 14.2 y; 51.8% males; 94% white), were compared with iDower-transformed 12-lead ECGs (both 1000 Hz), recorded in 8 patients with infarct-cardiomyopathy and sustained monomorphic ventricular tachycardia (VT) (age 68.0 +/- 7.8 y, 37.5% male, mean LVEF 29 +/- 12%). Normalized speed at 10 QRS segments was calculated as the distance traveled by the heart vector along the QRS loop in three-dimensional space, divided by 1/10th of the QRS duration. Curvature was calculated as the magnitude of the derivative of the QRS loop tangent vector divided by speed. Planarity was calculated as the mean of the dihedral angles between 2 consecutive planes for all planes generated for the median beat. Orbital frequency (a scalar measure of rotation rate of the QRS vector) was calculated as a product of speed and curvature. Results: Mixed regression analysis showed that speed was slower [6.6 (95%CI 4.4-8.9) vs. 24.6 (95%CI 11.5-37.7) mu V/ms; P < 0.00011; orbital frequency was smaller [1.4 (95%CI 1.2-1.6) vs. 6.8 (95%CI 5.4-8.1) ms(-1); P < 0.0001], and planarity was larger by 3.6 degrees (95%CI 1.4 degrees-5.8; P=0.002) in VT cases than in healthy controls. ROC AUC for orbital frequency was 0.940 (95%CI 0.935-0.944) across all frequencies and QRS segments. ROC AUC for planarity at 70-249 Hz was 0.995 (95%CI 0.985-1.00). ROC AUC for speed at 70-79 Hz was 0.979 (95%CI 0.969-0.989). Conclusion: This novel method reveals characteristic features of an abnormal electrophysiological substrate associated with VT. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Tereshchenko, Larisa G.; Kabir, Muammar; Ghafoori, Elyar] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA. [Waks, Jonathan W.; Shvilkin, Alexei; Josephson, Mark E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc Med, Boston, MA 02215 USA. RP Tereshchenko, LG (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA. EM tereshch@ohsu.edu OI Shvilkin, Alexei/0000-0003-3662-9938; Tereshchenko, Larisa/0000-0002-6976-1313 FU National Institute of Health [1R01HL118277] FX This research was supported in part by the National Institute of Health #1R01HL118277 (LGT and MEJ). NR 23 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0010-4825 EI 1879-0534 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD OCT 1 PY 2015 VL 65 BP 150 EP 160 DI 10.1016/j.compbiomed.2015.03.001 PG 11 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA CT5OW UT WOS:000362860700018 PM 25842361 ER PT J AU Kuhtreiber, WM Washer, SLL Hsu, E Zhao, M Reinhold, P Burger, D Zheng, H Faustman, DL AF Kuhtreiber, W. M. Washer, S. L. L. Hsu, E. Zhao, M. Reinhold, P., III Burger, D. Zheng, H. Faustman, D. L. TI Low levels of C-peptide have clinical significance for established Type 1 diabetes SO DIABETIC MEDICINE LA English DT Article ID BETA-CELL FUNCTION; COMPLICATIONS TRIAL; SERUM 1,5-ANHYDROGLUCITOL; SEVERE HYPOGLYCEMIA; ONSET; LONG; AGE; HYPERGLYCEMIA; PREVALENCE; DIAGNOSIS AB Aim To determine whether the low C-peptide levels (< 50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance. Methods We evaluated fasting C-peptide levels, duration of disease and age of onset in a large cross-sectional series (n = 1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C-peptide and HbA(1c) control (n = 1273), as well as diabetic complications (n = 324) and presence of hypoglycaemia (n = 323). The full range of C-peptide levels was also compared with 1,5-Anhydroglucitol, a glucose responsive marker. Results C-peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset (P < 0.0001), after adjusting for disease duration. C-peptide levels > 10 pmol/l were associated with protection from complications (e. g. nephropathy, neuropathy, foot ulcers and retinopathy; P = 0.03). Low C-peptide levels were associated with poor metabolic control measured by HbA(1c) (P < 0.0001). Severe hypoglycaemia was associated with the lowest C-peptide levels compared with mild (P = 0.049) or moderate (P = 0.04) hypoglycaemia. All levels of measurable C-peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5-Anhydroglucitol (P < 0.0001). Conclusions Low C-peptide levels have clinical significance and appear helpful in characterizing groups at-risk for faster C-peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C-peptide levels may be a biomarker for characterizing at-risk patients with Type 1 diabetes. C1 [Kuhtreiber, W. M.; Washer, S. L. L.; Hsu, E.; Zhao, M.; Reinhold, P., III; Burger, D.; Faustman, D. L.] Harvard Univ, Sch Med, Immunobiol Lab, Boston, MA 02115 USA. [Kuhtreiber, W. M.; Washer, S. L. L.; Hsu, E.; Zhao, M.; Reinhold, P., III; Burger, D.; Faustman, D. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zheng, H.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Faustman, DL (reprint author), Harvard Univ, Sch Med, Immunobiol Lab, Boston, MA 02115 USA. EM faustman@helix.mgh.harvard.edu FU Iacocca Foundation; NIH BADRC [P30 DK057521] FX This paper presents work supported by The Iacocca Foundation and NIH BADRC grant support (P30 DK057521) and we thank them for their generosity. NR 30 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 EI 1464-5491 J9 DIABETIC MED JI Diabetic Med. PD OCT PY 2015 VL 32 IS 10 BP 1346 EP 1353 DI 10.1111/dme.12850 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CT8DB UT WOS:000363044100016 PM 26172028 ER PT J AU Radulovic, M Schilero, GJ Yen, C Bauman, WA Wecht, JM Ivan, A La Fountaine, MF Korsten, MA AF Radulovic, M. Schilero, G. J. Yen, C. Bauman, W. A. Wecht, J. M. Ivan, A. La Fountaine, M. F. Korsten, M. A. TI Greatly increased prevalence of esophageal dysmotility observed in persons with spinal cord injury SO DISEASES OF THE ESOPHAGUS LA English DT Article DE esophageal motility; gastroesophageal reflux disease; high-resolution manometry; spinal cord injury ID GASTROESOPHAGEAL-REFLUX DISEASE; MOTILITY DISORDERS; ACID EXPOSURE; ABNORMALITIES; SPHINCTER; PRESSURE; CRITERIA; HUMANS AB The effects of spinal cord injury (SCI) on esophageal motility are largely unknown. Furthermore, due to the complete or partial loss of sensory innervation to the upper gastrointestinal tract, a symptom-based diagnosis of esophageal dysmotility is problematic in the SCI population. To determine the prevalence and characterize the type of motility disorders observed in persons with chronic SCI compared with that of able-bodied (AB) controls based on esophageal pressure topography isometrics acquired by high-resolution manometry and categorized by application of the Chicago Classification. High-resolution manometry of the esophagus was performed in 39 individuals: 14 AB, 12 with paraplegia (level of injury between T4-T12) and 13 with tetraplegia (level of injury between C5-C7). A catheter containing multiple pressure sensors arranged at 360 degrees was introduced into the esophagi of subjects at a distance that allowed visualization of both the upper esophageal sphincters (UES) and lower esophageal sphincters (LES). After a period to acquire pressures at baseline, subjects were asked to perform 10 wet swallows with 5-mL boluses of isotonic saline while esophageal pressure and impedance were being recorded. No significant differences were noted for gender, age, or body mass index between AB and SCI groups. Twenty-one of 25 (84%) subjects with SCI had at least one motility abnormality: 12% with Type II achalasia, 4% with Type III achalasia, 20% with esophagogastric junction outflow obstruction, 4% with the hypercontractile esophagus, and 48% with peristaltic abnormalities (weak peristalsis with small or large defects or frequent failed peristalsis). In contrast, only 7% (1 out of 14) of the AB subjects had any type of esophageal motility disorder. Despite the lack of subjective complaints and clinical awareness, esophageal dysmotility appears to be a highly prevalent condition in persons with SCI. The use of new and improved techniques, as well as a more stringent classification system, permitted the identification of the presence of nonspecific motility disorders in almost all SCI subjects, including four individuals who were previously undiagnosed with achalasia. Future work in persons with SCI is required to clarify the clinical impact of this observation and to study potential associations between esophageal dysmotility, gastroesophageal reflux disease, and pulmonary function. An increased awareness of esophageal dysfunction in the SCI population may lead to the development of new clinical guidelines for the diagnosis, prevention, and treatment of these largely unrecognized disorders. C1 [Radulovic, M.; Schilero, G. J.; Yen, C.; Bauman, W. A.; Wecht, J. M.; Ivan, A.; La Fountaine, M. F.; Korsten, M. A.] Natl Ctr Excellence Med Consequences Spinal Cord, Rehabil Res & Dev Serv, Bronx, NY USA. [Radulovic, M.; Schilero, G. J.; Bauman, W. A.; Korsten, M. A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Radulovic, M.; Schilero, G. J.; Bauman, W. A.; Korsten, M. A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Schilero, G. J.; Bauman, W. A.; Wecht, J. M.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [La Fountaine, M. F.] Seton Hall Univ, Sch Hlth & Med Sci, Essex Cty, NJ USA. RP Radulovic, M (reprint author), James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences SCI, Room 7A-13K 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM miroslav.radulovic@va.gov FU Department of Veterans Affairs Rehabilitation Research and Development Service [B9212-C]; James J. Peters VA Medical Center FX This research was supported by the Department of Veterans Affairs Rehabilitation Research and Development Service (Grants #B9212-C) and the James J. Peters VA Medical Center. NR 23 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1120-8694 EI 1442-2050 J9 DIS ESOPHAGUS JI Dis. Esophagus PD OCT PY 2015 VL 28 IS 7 BP 699 EP 704 DI 10.1111/dote.12272 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5ZU UT WOS:000362890600014 PM 25224683 ER PT J AU Abbate, R Al-Daghri, NM Andreozzi, P Borregaard, N Can, G Caridi, G Carstensen-Kirberg, M Cioni, G Conte, E Cuomo, R Denis, MA Fakhfouri, G Fakhfouri, G Fiasse, R Glenthoj, A Goliasch, G Gremmel, T Herder, C Iemmolo, M Jing, ZC Krause, R Marrone, O Miazgowski, B Miazgowski, T Minchiotti, L Mousavizadeh, K Ndrepepa, G Niessner, A Luque, CO Onat, A Papassotiriou, I Ortiz, MR Sabico, S Schooling, CM Sakka, SD Soltysiak, P Visseren, FLJ Wagner, J Wang, XJ Westerink, J AF Abbate, Rosanna Al-Daghri, Nasser M. Andreozzi, Paolo Borregaard, Niels Can, Gunay Caridi, Gianluca Carstensen-Kirberg, Maren Cioni, Gabriele Conte, Enrico Cuomo, Rosario Denis, Marie A. Fakhfouri, Gohar Fakhfouri, G. Fiasse, Renne Glenthoj, Andreas Goliasch, Georg Gremmel, Thomas Herder, Christian Iemmolo, Maria Jing, Zhi-Cheng Krause, Robert Marrone, Oreste Miazgowski, Bartosz Miazgowski, Tomasz Minchiotti, Lorenzo Mousavizadeh, Kazem Ndrepepa, Gjin Niessner, Alexander Ogayar Luque, Cristina Onat, Altan Papassotiriou, Ioannis Ruiz Ortiz, Martin Sabico, Shaun Schooling, C. Mary Sakka, Sophia D. Soltysiak, P. Visseren, Frank L. J. Wagner, Jasmin Wang, Xiao-Jian Westerink, Jan TI Research update for articles published in EJCI in 2013 SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CORONARY-ARTERY-DISEASE; NONALCOHOLIC FATTY LIVER; VISCERAL ADIPOSITY INDEX; HEREDITARY HEMORRHAGIC TELANGIECTASIA; SERUM URIC-ACID; COMPLICATING CROHNS-DISEASE; IRRITABLE-BOWEL-SYNDROME; BLOOD-STREAM INFECTIONS; OBSTRUCTIVE SLEEP-APNEA; ISCHEMIC-HEART-DISEASE C1 [Abbate, Rosanna; Cioni, Gabriele] Univ Florence, Dept Expt & Clin Med, Florence, Italy. [Al-Daghri, Nasser M.] King Saud Univ, Coll Sci, Dept Biochem, Prince Mutaib Chair Biomarkers Osteoporosis, Riyadh 11451, Saudi Arabia. [Andreozzi, Paolo; Cuomo, Rosario] Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy. [Borregaard, Niels; Glenthoj, Andreas] Natl Univ Hosp, Dept Hematol, Granulocyte Res Lab, Copenhagen, Denmark. [Can, Gunay] Istanbul Univ, Cerrahpasa Med Fac, Dept Cardiol, Istanbul, Turkey. [Can, Gunay] Istanbul Univ, Cerrahpasa Med Fac, Dept Publ Hlth, Istanbul, Turkey. [Caridi, Gianluca] Ist Giannina Gaslini IRCCS, Lab Pathophysiol Uremia, Genoa, Italy. [Carstensen-Kirberg, Maren; Herder, Christian] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany. [Carstensen-Kirberg, Maren; Herder, Christian] German Ctr Diabet Res DZD eV, Partner Dusseldorf, Dusseldorf, Germany. [Conte, Enrico; Iemmolo, Maria] Univ Catania, Dept Clin & Expt Med, Catania, Italy. [Denis, Marie A.; Fiasse, Renne] St Luc Univ Hosp, Dept Gastroenterol, Brussels, Belgium. [Fakhfouri, Gohar] Univ Laval, Fac Med, Dept Psychiat & Neurosci, Quebec City, PQ G1K 7P4, Canada. [Fakhfouri, G.] Inst Univ Sante Mentale Quebec, Quebec City, PQ, Canada. [Goliasch, Georg; Niessner, Alexander] Med Univ Vienna, Dept Internal Med 2, Div Cardiol, Vienna, Austria. [Gremmel, Thomas] Med Univ Vienna, Dept Internal Med 2, Vienna, Austria. [Gremmel, Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp,Ctr Platelet Res Studies,Di, Boston, MA 02115 USA. [Jing, Zhi-Cheng] Chinese Acad Med Sci, FuWai Hosp, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China. [Jing, Zhi-Cheng] Peking Union Med Coll, Beijing 100021, Peoples R China. [Krause, Robert; Wagner, Jasmin] Med Univ Graz, Dept Internal Med, Sect Infect Dis & Trop Med, Graz, Austria. [Marrone, Oreste] CNR, Inst Biomed & Mol Immunol, Palermo, Italy. [Miazgowski, Bartosz; Miazgowski, Tomasz; Soltysiak, P.] Pomeranian Med Univ, Dept Hypertens & Internal Med, Szczecin, Poland. [Minchiotti, Lorenzo] Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy. [Mousavizadeh, Kazem] Iran Univ Med Sci, Fac Adv Technol Med, Cellular & Mol Res Ctr, Tehran, Iran. [Mousavizadeh, Kazem] Iran Univ Med Sci, Fac Adv Technol Med, Dept Mol Med, Tehran, Iran. [Ndrepepa, Gjin] Deutsch Herzzentrum Munich, Munich, Germany. [Ogayar Luque, Cristina] Cruz Roja Hosp, Emergency Dept, Cordoba, Spain. [Papassotiriou, Ioannis] Aghia Sophia Childrens Hosp, Dept Clin Biochem, Athens, Greece. [Ruiz Ortiz, Martin] Reina Sofia Univ Hosp, Dept Cardiol, Cordoba, Spain. [Sabico, Shaun] King Saud Univ, Coll Sci, Dept Biochem, Biomarkers Res Program, Riyadh 11451, Saudi Arabia. [Schooling, C. Mary] CUNY, Sch Publ Hlth, New York, NY 10021 USA. [Schooling, C. Mary] CUNY Hunter Coll, New York, NY 10021 USA. [Sakka, Sophia D.] Birmingham Childrens Hosp, Dept Endocrinol & Diabet, Birmingham, W Midlands, England. [Visseren, Frank L. J.; Westerink, Jan] Univ Med Ctr Utrecht, Dept Vasc Med, Utrecht, Netherlands. RP Abbate, R (reprint author), Univ Florence, Dept Expt & Clin Med, Florence, Italy. RI Andreozzi, Paolo/M-4404-2015; Caridi, Gianluca/F-7052-2010; Cuomo, Rosario/C-3446-2011; Miazgowski, Tomasz/H-9448-2014; OI Gremmel, Thomas/0000-0001-9554-7292; Andreozzi, Paolo/0000-0002-4604-0126; Caridi, Gianluca/0000-0001-6700-3001; Cuomo, Rosario/0000-0003-0768-8381; Glenthoj, Andreas/0000-0003-2082-0738; mousavizadeh, kazem/0000-0002-4213-5523; Marrone, Oreste/0000-0001-6819-7928 FU Deanship of Scientific Research at King Saud University, Riyadh, Saudi Arabia [PRG-1436-15] FX The authors Shaun Sabico and Nasser M. Al-Daghri thank the support of the Deanship of Scientific Research at King Saud University, Riyadh, Saudi Arabia [Prolific Research Group (PRG-1436-15)]. G. Cioni and A. M. Gori from the Department of Experimental and Clinical Medicine, University of Florence, Florence Italy contributed to the collection of new, unpublished data on 'Nonalcoholic fatty liver in nondiabetic patients with acute coronary syndromes'. NR 96 TC 1 Z9 1 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 EI 1365-2362 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD OCT PY 2015 VL 45 IS 10 BP 1005 EP 1016 DI 10.1111/eci.12512 PG 12 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CT8DK UT WOS:000363045000001 PM 26394055 ER PT J AU de Leeuw, C Goudriaan, A Smit, AB Yu, DM Mathews, CA Scharf, JM Verheijen, MHG Posthuma, D AF de Leeuw, Christiaan Goudriaan, Andrea Smit, August B. Yu, Dongmei Mathews, Carol A. Scharf, Jeremiah M. Verheijen, Mark H. G. Posthuma, Danielle CA Tourette Syndrome Assoc Int Consor TI Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID POSTSYNAPTIC DENSITY; BRAIN; SCHIZOPHRENIA; PROTEOMICS; PROTEINS AB Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls. The gene sets included specific synaptic, astrocytic, oligodendrocyte and microglial functions. We report association of Tourette syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte-neuron metabolic coupling may be an important contributor to Tourette syndrome pathogenesis. C1 [de Leeuw, Christiaan; Posthuma, Danielle] Vrije Univ Amsterdam, Dept Complex Trait Genet, Med Ctr, NL-1081 HV Amsterdam, Netherlands. [de Leeuw, Christiaan] Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 ED Nijmegen, Netherlands. [Goudriaan, Andrea; Smit, August B.; Verheijen, Mark H. G.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Mol & Cellular Neurobiol, NL-1081 HV Amsterdam, Netherlands. [Yu, Dongmei; Scharf, Jeremiah M.] Harvard Univ, Sch Med, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02115 USA. [Yu, Dongmei; Scharf, Jeremiah M.] Harvard Univ, Sch Med, Dept Neurol, Ctr Human Genet Res,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, Inst Human Genet, San Francisco, CA USA. [Scharf, Jeremiah M.] Harvard Univ, Sch Med, Dept Neurol, Div Cognit & Behav Neurol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Tourette Syndrome Assoc Int Consor] Tourette Syndrome Assoc, Bayside, NY USA. [Posthuma, Danielle] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, NL-1081 HV Amsterdam, Netherlands. [Posthuma, Danielle] Erasmus Univ, Sophia Child Hosp, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. RP Verheijen, MHG (reprint author), Vrije Univ Amsterdam, Dept Complex Trait Genet, De Boelelaan 1085, NL-1081 HV Amsterdam, Netherlands. EM mark.verheijen@vu.nl; danielle.posthuma@vu.nl RI reus, victor/I-7923-2015 OI reus, victor/0000-0002-8193-5697 FU David Judah Fund, NIH [NS40024]; Tourette Syndrome Association International Consortium for Genetics, NIH [NS16648]; Tourette Syndrome Association; American Recovery and Reinvestment Act (ARRA) [NS40024-07S1, NS16648-29S1]; NIH [NS037484, MH085057, HHSN268200782096C]; National Center for Research Resources [U54 RR020278]; New Jersey Center for Tourette Syndrome & Associated Disorders (through New Jersey Department of Health and Senior Services) [08-1827-FS-N-0]; NIH Genes, Environment and Health Initiative (GEI) [U01 HG004422]; Gene Environment Association Studies (GENEVA) under GEI; Johns Hopkins University Center for Inherited Disease Research; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Netherlands Scientific Organization [NWO 480-05-003]; NWO [645.000.003]; TOP ZonMW [40-00812-98-07-032]; HEALTH-2009-2.1.2-1 EU-FP7 Synsys project [242167] FX We are grateful to all the patients with Tourette syndrome who generously agreed to participate in this study. Furthermore, the members of the Tourette Syndrome Association International Consortium for Genetics are deeply indebted to the Tourette Syndrome Association for their guidance and support. This work was supported by a grant from the David Judah Fund, NIH grants NS40024 to DLP, JMS and the Tourette Syndrome Association International Consortium for Genetics, NIH grant NS16648 and a grant from the Tourette Syndrome Association to DLP, American Recovery and Reinvestment Act (ARRA) Grants NS40024-07S1 to DLP/JMS and NS16648-29S1 to DLP, NIH grant NS037484 to NBF and NIH grant MH085057 to JMS. The Broad Institute Center for Genotyping and Analysis was supported by grant U54 RR020278 from the National Center for Research Resources. Support was also provided by the New Jersey Center for Tourette Syndrome & Associated Disorders (through New Jersey Department of Health and Senior Services: 08-1827-FS-N-0) to GAH and JAT. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative (GEI) (U01 HG004422). SAGE is one of the GWAS funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for the collection of data sets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392), and the Family Study of Cocaine Dependence (FSCD; R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' (HHSN268200782096C). The data sets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0 00092.v1.p1 through dbGaP accession number phs000092.v1.p. Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003). We gratefully acknowledge financial support by NWO via the Complexity project (645.000.003) and TOP ZonMW (40-00812-98-07-032). ABS and DP received funding from the HEALTH-2009-2.1.2-1 EU-FP7 Synsys project (grant number 242167). NR 20 TC 4 Z9 4 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD OCT PY 2015 VL 23 IS 11 BP 1519 EP 1522 DI 10.1038/ejhg.2015.22 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CT6IH UT WOS:000362916200016 PM 25735483 ER PT J AU Wilkins, JM AF Wilkins, James M. TI More Than Capacity: Alternatives for Sexual Decision Making for Individuals With Dementia SO GERONTOLOGIST LA English DT Article DE Autonomy; Ethics; Nursing homes; Person centered care ID CONSENT CAPACITY; ADVANCE DIRECTIVES; NURSING-HOME; OLDER-ADULTS; HEALTH; CARE; ASSESSMENTS; RESIDENTS AB Sexual expression can be an important aspect of well being for older adults with dementia living in nursing homes. There is a tension in the nursing home, however, between ensuring autonomy of residents for sexual expression and protecting residents from harm. To alleviate this tension, nursing homes can conduct an assessment of residents' capacity for sexual consent. This article argues that although such assessments can be useful in the initial evaluation of capacity, this is a somewhat flawed approach to sexual decision making and a finding of incapacity should not necessarily preclude sexual expression. In instances where residents are found to lack capacity but continue to express interest in sexual expression, a committee approach can be utilized where residents, the nursing home, and family members can convene to advocate for residents' autonomy, dignity, and right to sexual expression while working to minimize harm. Such advocacy decisions can be based on substituted judgment, a best interest standard, or some combination of the two. Although committee decision making for sexual expression seems intrusive, it at least allows for continued discussion of the right to sexual freedom for residents in the face of significant counterbalancing forces. C1 [Wilkins, James M.] McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. [Wilkins, James M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wilkins, James M.] Harvard Univ, Sch Med, Boston, MA USA. RP Wilkins, JM (reprint author), McLean Hosp, Adult Outpatient Clin, 115 Mill St, Belmont, MA 02478 USA. EM jwilkins1@partners.org NR 40 TC 4 Z9 4 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2015 VL 55 IS 5 BP 716 EP 723 DI 10.1093/geront/gnv098 PG 8 WC Gerontology SC Geriatrics & Gerontology GA CT7HC UT WOS:000362984500002 PM 26315314 ER PT J AU Rauh-Hain, JA Diver, E Meyer, LA Clemmer, J Lu, KH del Carmen, MG Schorge, JO AF Rauh-Hain, J. Alejandro Diver, Elisabeth Meyer, Larissa A. Clemmer, Joel Lu, Karen H. del Carmen, Marcela G. Schorge, John O. TI Patterns of care, associations and outcomes of chemotherapy for uterine serous carcinoma: Analysis of the National Cancer Database SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial cancer; Uterine serous carcinoma ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; ADVANCED ENDOMETRIAL CARCINOMA; WHOLE-ABDOMINAL IRRADIATION; STAGE-I; CLEAR-CELL; ADJUVANT CHEMOTHERAPY; MEDICARE POPULATION; RACIAL DISPARITIES; RADIATION-THERAPY AB Objective. Evaluate rates of chemotherapy and radiotherapy delivery in the treatment of uterine serous carcinoma, and compare clinical outcomes of treated and untreated patients. Methods. The National Cancer Database was queried to identify patients diagnosed with uterine serous carcinoma between 2003 and 2011. The impact of chemotherapy on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. Results. A total of 13,752 patients met the study eligibility criteria. Stage I, II, III, and IV disease accounted for 4355 (31.7%), 1023 (7.4%), 3484 (253%), and 2451 (17.8%) of the study population, respectively. 2439 (17.7%) women had unknown stage. Chemotherapy was administered in 4290 (35.4%) patients, radiotherapy to 1673 (12.2%), adjuvant chemo-radiation to 2915(21.2%), and 4874(35.4%) of women did not receive adjuvant therapy during the study period. Utilization of chemotherapy became more frequent over time. Over the entire study period, after adjusting for age, period of diagnosis, race, facility location, facility type, insurance provider, socioeconomic status, comorbidity index, lymph node dissection, treatment modality, and stage, there was an association between treatment modality and survival, with the lowest hazard ratio in patients that received chemoradiation. After adjusting for the same factors in women with stages I and II, chemo-radiation was associated with improved survival compared to patients that received no treatment. Radiotherapy or chemotherapy alone was not associated with improved survival. Conclusion. Utilization of chemotherapy is increased in this population over the study period from 2003-2012 and more importantly that survival, particularly in advanced stage patients, is improving. (C) 2015 Elsevier Inc. All rights reserved. C1 [Rauh-Hain, J. Alejandro; Diver, Elisabeth; Clemmer, Joel; del Carmen, Marcela G.; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA USA. [Meyer, Larissa A.; Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. RP Schorge, JO (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Div Gynecol Oncol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM jschorge@partners.org FU Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital FX This work was supported by The Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital. NR 43 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2015 VL 139 IS 1 BP 77 EP 83 DI 10.1016/j.ygyno.2015.08.016 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CT6ND UT WOS:000362928800013 PM 26325526 ER PT J AU Rauh-Hain, JA Starbuck, KD Meyer, LA Clemmer, J Schorge, JO Lu, KH del Carmen, MG AF Rauh-Hain, J. Alejandro Starbuck, Kristen D. Meyer, Larissa A. Clemmer, Joel Schorge, John O. Lu, Karen H. del Carmen, Marcela G. TI Patterns of care, predictors and outcomes of chemotherapy for uterine carcinosarcoma: A National Cancer Database analysis SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial cancer; Uterine carcinosarcoma; Chemotherapy ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; MIXED MULLERIAN TUMORS; RESECTED STAGE-I; ENDOMETRIAL CANCER; ELDERLY-WOMEN; UTERUS; IFOSFAMIDE; SURVIVAL; CISPLATIN AB Objective. Evaluate rates of chemotherapy and radiotherapy delivery in the treatment of uterine carcinosarcoma, and compare clinical outcomes of treated and untreated patients. Methods. The National Cancer Database was queried to identify patients diagnosed with uterine carcinosarcoma between 2003 and 2011. The impact of chemotherapy on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. Results. A total of 10,609 patients met study eligibility criteria. Stages 1,11,111, and IV disease accounted for 2997 (28.2%), 642 (6.1%), 2037 (19.2%), and 1316 (12.4%) of the study population, respectively. Most patients (91.0%) underwent definitive surgery, and lymphadenectomy was performed in 68.7% of the patients. Chemotherapy was administered in 2378 (22.4%) patients, radiotherapy to 2196 (20.7%), adjuvant chemo-radiation to 1804(17.0%), and 4231 (39.9%) of women did not received adjuvant therapy. Utilization of chemotherapy became more frequent overtime. Over the entire study period, after adjusting for race, period of diagnosis, facility location, facility type, insurance provider, stage, age, treatment modality, lymph node dissection, socioeconomic status, and comorbidity index, there was an association between treatment modality and survival. The lowest hazard ratio observed was in patients that received chemo-radiation. The strongest quantitative predictor of death was stage at the time of diagnosis. In addition, surgical treatment, lymph node dissection, most recent time-periods, lower comorbidity index, and higher socioeconomic status were associated with improved survival. Conclusion. The overall rates of chemotherapy use have increased over time. Adjuvant chemotherapy and chemo-radiation were associated with improved survival. (C) 2015 Elsevier Inc. All rights reserved. C1 [Rauh-Hain, J. Alejandro; Starbuck, Kristen D.; Clemmer, Joel; Schorge, John O.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA USA. [Meyer, Larissa A.; Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Div Gynecol Oncol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org OI Starbuck, Kristen/0000-0003-2294-2915 FU Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital FX This work was supported by The Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital. NR 34 TC 2 Z9 2 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2015 VL 139 IS 1 BP 84 EP 89 DI 10.1016/j.ygyno.2015.08.014 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CT6ND UT WOS:000362928800014 PM 26307402 ER PT J AU Elias, KM Emori, MM Papp, E MacDuffie, E Konecny, GE Velculescu, VE Drapkin, R AF Elias, Kevin M. Emori, Megan M. Papp, Eniko MacDuffie, Emily Konecny, Gottfried E. Velculescu, Victor E. Drapkin, Ronny TI Beyond genomics: Critical evaluation of cell line utility for ovarian cancer research SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Cell line model; Xenograft; Genomics ID IN-VIVO; CARCINOMA AB Objective. Comparisons of The Cancer Genome Atlas (TCGA) with high grade serous ovarian cancer (HGSOC) cell lines used in research reveal that many common experimental models lack defining genomic characteristics seen in patient tumors. As cell lines exist with higher genomic fidelity to TCGA, this study aimed to evaluate the utility of these cell lines as tools for preclinical investigation. Methods. We compared two HGSOC cell lines with supposed high genomic fidelity to TCGA, KURAMOCHI and OVSAHO, with the most commonly cited ovarian cancer cell line, SKOV3, which has poor genomic fidelity to TCGA. The lines were analyzed for genomic alterations, in vitro performance, and growth in murine xenografts. Results. Using targeted next generation sequencing analyses, we determined that each line had a distinct mutation profile, including alterations in TP53, and copy number variation of specific genes. KURAMOCHI and OVSAHO better recapitulated serous carcinoma morphology than SKOV3. All lines expressed PAX8 and stathmin, but KURAMOCHI and OVSAHO did not express CK7. KURAMOCHI was significantly more platinum sensitive than OVSAHO and SKOV3. Unlike SKOV3, KURAMOCHI and OVSAHO engrafted poorly in subcutaneous xenografts. KURAMOCHI and OVSAHO grew best after intraperitoneal injection in SCID mice and recapitulated miliary disease while SKOV3 grew in all murine systems and formed oligometastatic disease. Conclusions. The research utility of HGSOC cell line models requires a comprehensive assessment of genomic as well as in vitro and in vivo properties. Cell lines with closer genomic fidelity to human tumors may have limitations in performance for preclinical investigation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Elias, Kevin M.; Emori, Megan M.; MacDuffie, Emily; Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. [Elias, Kevin M.] Brigham & Womens Hosp, Dept Obstet & Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. [Elias, Kevin M.; Drapkin, Ronny] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Emori, Megan M.] Harvard Univ, Grad Sch Arts & Sci, Cambridge, MA 02138 USA. [Papp, Eniko; Velculescu, Victor E.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Konecny, Gottfried E.] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. RP Drapkin, R (reprint author), Univ Penn, Perelman Sch Med, Dept Obstet & Gynecol, Penn Ovarian Canc Res Ctr, Biomed Res Bldg Rm 1215,421 Curie Blvd, Philadelphia, PA 19104 USA. EM rdrapkin@mail.med.upenn.edu RI Drapkin, Ronny/E-9944-2016; OI Drapkin, Ronny/0000-0002-6912-6977; Elias, Kevin/0000-0003-1502-5553 FU Ruth N. White Research Fellowship in Gynecologic Oncology; Sperling Family Fund Fellowship; Robert and Deborah First Fund; Ruth L. Kirschstein National Research Service Award [F31-CA176995-01A1]; National Cancer Institute at the NIH [P50-CA083636]; NIH [U01-CA152990, R21-CA156021, CA121113]; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Honorable Tina Brozman Foundation; Gamel Family Ovarian Cancer Research Fund; Commonwealth Foundation FX This work was supported by the Ruth N. White Research Fellowship in Gynecologic Oncology (KME), the Sperling Family Fund Fellowship (KME), the Robert and Deborah First Fund (KME, RD), the Ruth L. Kirschstein National Research Service Award F31-CA176995-01A1 (MME), the National Cancer Institute at the NIH P50-CA083636 (RD), NIH U01-CA152990 (RD), NIH R21-CA156021 (RD), CA121113 (VEV), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (RD, VEV, GK), the Honorable Tina Brozman Foundation (RD), and the Gamel Family Ovarian Cancer Research Fund (RD), and the Commonwealth Foundation (VEV). NR 20 TC 15 Z9 15 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2015 VL 139 IS 1 BP 97 EP 103 DI 10.1016/j.ygyno.2015.08.017 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CT6ND UT WOS:000362928800016 PM 26321251 ER PT J AU Novak, M Lester, J Karst, AM Parkash, V Hirsch, MS Crum, CP Karlan, BY Drapkin, R AF Novak, Marian Lester, Jenny Karst, Alison M. Parkash, Vinita Hirsch, Michelle S. Crum, Christopher P. Karlan, Beth Y. Drapkin, Ronny TI Stathmin 1 and p16(INK4A) are sensitive adjunct biomarkers for serous tubal intraepithelial carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian; Serous; Fallopian tube; STIC; Stathmin; p16 ID OVARIAN-CANCER; MUTATION CARRIERS; FALLOPIAN-TUBES; SALPINGO-OOPHORECTOMY; POSITIVE WOMEN; P16 EXPRESSION; BRCA1; RISK; TUMOR; P53 AB Objective. To credential Stathmin 1 (STMN1) and p(16INK4A) (p16) as adjunct markers for the diagnosis of serous tubal intraepithelial carcinoma (STIC), and to compare STMN1 and p16 expression in p53-positive and p53-negative STIC and invasive high-grade serous carcinoma (HGSC). Methods. Immunohistochemistry (IHC) was used to examine STMN1 and p16 expression in fallopian tube specimens (n = 31) containing p53-positive and p53-negative STICs, invasive HGSCs, and morphologically normal FTE (fallopian tube epithelium). STMN1 and p16 expression was scored semiquantitatively by four individuals. The semiquantitative scores were dichotomized, and reported as positive or negative. Pooled siRNA was used to knockdown p53 in a panel of cell lines derived from immortalized FIE and HGSC. Results. STMN1 and p16 were expressed in the majority of p53-positive and p53-negative STICs and concomitant invasive HGSCs, but only scattered positive cells were present in morphologically normal FTE. Both proteins were expressed consistently across multiple STICs from the same patient and in concomitant invasive HGSC. Knockdown of p53 in immortalized FTE cells and in four HGSC-derived cell lines expressing different missense p53 mutations did not affect STMN1 protein levels. Conclusions. This study demonstrates that STMN1 and p16 are sensitive and specific adjunct biomarkers that, when used with p53 and Ki-67, improve the diagnostic accuracy of STIC. The addition of STMN1 and p16 helps to compensate for practical limitations of p53 and Ki-67 that complicate the diagnosis in up to one third of STICs. (C) 2015 Elsevier Inc. All rights reserved. C1 [Novak, Marian; Karst, Alison M.; Drapkin, Ronny] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lester, Jenny; Karlan, Beth Y.] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Parkash, Vinita] Yale Univ, Dept Pathol, New Haven, CT USA. [Hirsch, Michelle S.; Crum, Christopher P.; Drapkin, Ronny] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Div Womens & Perinatal Pathol, Boston, MA 02115 USA. RP Drapkin, R (reprint author), Univ Penn, Perelman Sch Med, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. EM rdrapkin@mail.med.upenn.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU National Institutes of Health: Pacific Ovarian Cancer Research Consortium NCI [P50 CA083636, R21 CA156021, U01 CA152990]; Miriam and Sheldon G. Adelson Medical Research Foundation; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; Honorable Tina Brozman Foundation FX This work was supported by grants from the National Institutes of Health: Pacific Ovarian Cancer Research Consortium NCI P50 CA083636 (BYK, RD), R21 CA156021 (RD) and U01 CA152990 (RD); a Miriam and Sheldon G. Adelson Medical Research Foundation Grant (RD), American Cancer Society Early Detection Professorship SIOP-06-258-01-COUN (BYK), and the Honorable Tina Brozman Foundation (RD). We thank Dr. Kai Doberstein for reviewing the manuscript. NR 30 TC 12 Z9 12 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2015 VL 139 IS 1 BP 104 EP 111 DI 10.1016/j.ygyno.2015.07.100 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CT6ND UT WOS:000362928800017 PM 26206555 ER PT J AU Pawar, PS Nagler, EM Gupta, PC Stoddard, AM Lando, HA Shulman, L Pednekar, MS Kasisomayajula, V Aghi, MB Sinha, DN Sorensen, GS AF Pawar, P. S. Nagler, E. M. Gupta, P. C. Stoddard, A. M. Lando, H. A. Shulman, L. Pednekar, M. S. Kasisomayajula, V. Aghi, M. B. Sinha, D. N. Sorensen, G. S. TI Tracking intervention delivery in the 'Tobacco-Free Teachers/Tobacco-Free Society' program, Bihar, India SO HEALTH EDUCATION RESEARCH LA English DT Article ID DIRECTIONS-SMALL-BUSINESS; SOCIAL-CONTEXTUAL MODEL; HEALTHY-DIRECTIONS; SCHOOL-PERSONNEL; WORKING-CLASS; MULTIETHNIC POPULATIONS; PRIMARY PREVENTION; CANCER PREVENTION; BEHAVIOR-CHANGE; ORAL-CANCER AB In health education and behavior change interventions, process tracking monitors the delivery of an intervention and its receipt to the intended audience. A randomized controlled trial in the state of Bihar, India was conducted to help school teachers become tobacco free through appropriately designed intervention program and delivery system. We describe the results from process tracking of this intervention delivery. The intervention program was centred on six topics delivered in each school through 12 sessions over 6 successive months. The program deliverers recorded the process measures as total number of sessions and program-components implemented (fidelity); time spent conducting sessions (dose) and proportion of teachers attending at least one session (reach). The outcome measures (teachers' exposure to intervention messages and tobacco policy adoption) were assessed post-intervention. All 12 sessions were delivered in 33 out of 36 schools. Thirty-one schools implemented all six program components. In 18 schools, >= 95% of the teachers participated in one or more sessions. Thirty-three schools received 12 or more hours of dose. In 29 schools, 100% teachers reported exposure to all program messages. Tobacco policy was adopted by all schools. Thus, the intervention was generally delivered as planned and it had a positive impact on teachers and schools. C1 [Pawar, P. S.; Gupta, P. C.; Pednekar, M. S.; Aghi, M. B.] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai 400701, India. [Nagler, E. M.; Shulman, L.; Kasisomayajula, V.; Sorensen, G. S.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Nagler, E. M.; Shulman, L.; Kasisomayajula, V.; Sorensen, G. S.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Stoddard, A. M.] Biostat Consultant, Pelham, MA 01002 USA. [Lando, H. A.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Sinha, D. N.] Sch Prevent Oncol, Patna 800001, Bihar, India. RP Pawar, PS (reprint author), Healis Sekhsaria Inst Publ Hlth, Navi Mumbai 400701, India. EM drpratibhak@gmail.com FU National Cancer Institute at the National Institutes of Health [5R01 CA120958, 5K05 A108663] FX This work was supported by the National Cancer Institute at the National Institutes of Health (5R01 CA120958, 5K05 A108663). NR 29 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 EI 1465-3648 J9 HEALTH EDUC RES JI Health Educ. Res. PD OCT PY 2015 VL 30 IS 5 BP 731 EP 741 DI 10.1093/her/cyv039 PG 11 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA CT7KC UT WOS:000362992600005 PM 26342136 ER PT J AU Gonzalez, M Falk, MJ Gai, XW Postrel, R Schule, R Zuchner, S AF Gonzalez, Michael Falk, Marni J. Gai, Xiaowu Postrel, Richard Schuele, Rebecca Zuchner, Stephan TI Innovative Genomic Collaboration Using the GENESIS (GEM.app) Platform SO HUMAN MUTATION LA English DT Article DE next-generation sequencing; data sharing; exome; Mendelian disease; matchmaker exchange ID DISEASE AB Next-generation sequencing has led to an unparalleled pace of Mendelian disease gene discovery in recent years. To address the challenges of analysis and sharing of large datasets, we had previously introduced the collaborative web-based GEM.app software [Gonzalez et al., 2013]. Here, we are presenting the results of using GEM.app over nearly 3 years and introducing the next generation of this platform. First, GEM.app has been renamed to GENESIS since it is now part of "The Genesis Project" (501c3), a not-for-profit foundation that is committed to providing the best technology to enable research scientists and to connecting patients and clinicians to genomic information. Second, GENESIS (GEM.app) has grown to nearly 600 registered users from 44 countries, who have collectively achieved 62 gene identifications or published studies that have expanded phenotype/genotype correlations. Our concept of user-driven data sharing and matchmaking is now the main cause for gene discoveries within GENESIS. In many of these findings, researchers from across the globe have been connected, which gave rise to the genetic evidence needed to successfully pinpoints-pecific gene mutations that explained patients' disease. Here, we present an overview of the various novel insights that have been made possible through the data-sharing capabilities of GENESIS/GEM.app. (C) 2015 Wiley Periodicals, Inc. C1 [Gonzalez, Michael; Postrel, Richard] Genesis Project Inc, Miami, FL 33136 USA. [Falk, Marni J.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA. [Falk, Marni J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gai, Xiaowu] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Schuele, Rebecca] Univ Tubingen, Ctr Neurol, Tubingen, Germany. [Schuele, Rebecca] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany. [Schuele, Rebecca; Zuchner, Stephan] Univ Miami, Miller Sch Med, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL 33136 USA. [Schuele, Rebecca; Zuchner, Stephan] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. RP Zuchner, S (reprint author), Univ Miami, Miller Sch Med, 1501 NW 10th Ave, Miami, FL 33136 USA. EM szuchner@med.miami.edu FU NIH [R01NS075764, 5R01NS072248, U54NS065712]; CMT Association; Muscular Dystrophy Association; European Union (within the 7th European Community Framework Program through funding for the E-Rare Network NEU-ROLIPID [01GM1408B]; Marie Curie International Outgoing Fellowship [PIOFGA-2012-326681]; United Mitochondrial Disease Foundation; National Institutes of Health [U54-NS078059]; North American Mitochondrial Disease Consortium, pilot award [NAMDC7407, U41-HG006834] FX Contract grant sponsors: NIH R01NS075764; 5R01NS072248; and U54NS065712; CMT Association; Muscular Dystrophy Association; European Union (within the 7th European Community Framework Program through funding for the E-Rare Network NEU-ROLIPID; 01GM1408B); Marie Curie International Outgoing Fellowship (grant PIOFGA-2012-326681); "The United Mitochondrial Disease Foundation"; "National Institutes of Health (U54-NS078059-North American Mitochondrial Disease Consortium, pilot award #NAMDC7407; U41-HG006834). NR 9 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD OCT PY 2015 VL 36 IS 10 SI SI BP 950 EP 956 DI 10.1002/humu.22836 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CT7IX UT WOS:000362989500005 PM 26173844 ER PT J AU Krishnan, K Ge, L Haraldsson, H Hope, MD Saloner, DA Guccione, JM Tseng, EE AF Krishnan, Kapil Ge, Liang Haraldsson, Henrik Hope, Michael D. Saloner, David A. Guccione, Julius M. Tseng, Elaine E. TI Ascending thoracic aortic aneurysm wall stress analysis using patient-specific finite element modeling of in vivo magnetic resonance imaging SO INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY LA English DT Article DE Ascending thoracic aortic aneurysm; Wall stress; Finite element analysis ID INTERNATIONAL REGISTRY; INTIMAL TEARS; DISSECTION; VALVE; PATHOGENESIS; FLOW; ROOT AB OBJECTIVES: Rupture/dissection of ascending thoracic aortic aneurysms (aTAAs) carries high mortality and occurs in many patients who did not meet size criteria for elective surgery. Elevated wall stress may better predict adverse events, but cannot be directly measured in vivo, rather determined from finite element (FE) simulations. Current computational models make assumptions that limit accuracy, most commonly using in vivo imaging geometry to represent zero-pressure state. Accurate patient-specific wall stress requires models with zero-pressure three-dimensional geometry, material properties, wall thickness and residual stress. We hypothesized that wall stress calculated from in vivo imaging geometry at systemic pressure underestimates that using zero-pressure geometry. We developed a novel method to derive zero-pressure geometry from in vivo imaging at systemic pressure. The purpose of this study was to develop the first patient-specific aTAA models using magnetic resonance imaging (MRI) to assess material properties and zero-pressure geometry. Wall stress results from FE models using systemic pressure were compared with those from models using zero-pressure correction. METHODS: Patients with aTAAs <5 cm underwent ECG-gated computed tomography angiography (CTA) and displacement encoding with stimulated echo (DENSE)-MRI. CTA lumen geometry was used to create surface contour meshes of aTAA geometry. DENSE-MRI measured cyclic aortic wall strain from which wall material property was derived. Zero-and systemic pressure geometries were created. Simulations were loaded to systemic pressure using the ABAQUS FE software. Wall stress analyses were compared between zero-pressure-corrected and systemic pressure geometry FE models. RESULTS: Peak first principal wall stress (primarily aligned in the circumferential direction) at systolic pressure for the zero-pressure correction models was 430.62 +/- 69.69 kPa, whereas that without zero-pressure correction was 312.55 +/- 39.65 kPa (P = 0.004). Peak second principal wall stress (primarily aligned in the longitudinal direction) at systolic pressure for the zero-pressure correction models was 200.77 +/- 43.13 kPa, whereas that without zero-stress correction was 156.25 +/- 25.55 kPa (P = 0.02). CONCLUSIONS: Previous FE aTAA models from in vivo CT and MRI have not accounted for zero-pressure geometry or patient-specific material property. We demonstrated that zero-pressure correction significantly impacts wall stress results. Future computational models that use wall stress to predict aTAA adverse events must take into account zero-pressure geometry and patient material property for accurate wall stress determination. C1 [Krishnan, Kapil; Ge, Liang; Guccione, Julius M.; Tseng, Elaine E.] Univ Calif San Francisco, Med Ctr, Dept Surg, San Francisco, CA 94143 USA. [Krishnan, Kapil; Ge, Liang; Haraldsson, Henrik; Hope, Michael D.; Saloner, David A.; Guccione, Julius M.; Tseng, Elaine E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Haraldsson, Henrik; Hope, Michael D.; Saloner, David A.] Univ Calif San Francisco, Med Ctr, Dept Radiol, San Francisco, CA 94143 USA. RP Tseng, EE (reprint author), Univ Calif San Francisco, Med Ctr, Div Cardiothorac Surg, 500 Parnassus Ave,Suite 405W,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org FU University of California [246590] FX This work was supported by the University of California, proof-of-concept grant 246590. NR 26 TC 4 Z9 5 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1569-9293 EI 1569-9285 J9 INTERACT CARDIOV TH JI Interact Cardiovasc. Thorac. Surg. PD OCT PY 2015 VL 21 IS 4 BP 471 EP 480 DI 10.1093/icvts/ivv186 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT8HU UT WOS:000363056800016 PM 26180089 ER PT J AU Hou, LF Wang, T Sun, JR AF Hou, Lifei Wang, Tian Sun, Jiaren TI gamma delta T cells in infection and autoimmunity SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE gamma delta T cells; IL-17; IFN-gamma; Infection; Autoimmunity ID WEST-NILE-VIRUS; CENTRAL-NERVOUS-SYSTEM; INNATE LYMPHOID-CELLS; IFN-GAMMA; NEUTROPHIL RECRUITMENT; IMMUNE-RESPONSES; INTERFERON-GAMMA; IL-17 PRODUCTION; FETAL THYMUS; PIVOTAL ROLE AB Standing at the interface of innate and adaptive immune, gamma delta T cells play important pathophysiologic roles in infection, autoimmunity, and tumorigenesis. Recent studies indicate that gamma delta T cells could be categorized into IFN-gamma(+) and IL-17(+) subsets, both of which possess select TCR usages, bear unique surface markers and require different cytokine signaling to maintain the homeostasis. In addition, as the major innate IL-17 producers, gamma delta T cells are increasingly appreciated for their involvement in various acute infections and injuries. This review will summarize the characteristics of IFN-gamma(+) (gamma delta T-IFN-gamma) and IL-17(+) gamma delta T cells (gamma delta T17) and discuss their distinct pathogenic functions in different disease models. (C) 2015 Elsevier B.V. All rights reserved. C1 [Hou, Lifei; Wang, Tian; Sun, Jiaren] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. RP Hou, LF (reprint author), Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM Lifei.Hou@childrens.harvard.edu; jisun@utmb.edu FU NIH [AI109100] FX We thank Ms. Mardelle Susman for assistance with manuscript preparation. This work was supported in part by NIH grant AI109100. NR 69 TC 2 Z9 2 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 EI 1878-1705 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD OCT PY 2015 VL 28 IS 2 SI SI BP 887 EP 891 DI 10.1016/j.intimp.2015.03.038 PG 5 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA CT5NT UT WOS:000362857800012 PM 25864620 ER PT J AU Neel, V AF Neel, Victor TI Bringing Diagnostic Optical Technologies Into the Clinic SO JAMA DERMATOLOGY LA English DT Editorial Material ID BASAL-CELL CARCINOMA; CONFOCAL MICROSCOPY; CANCER C1 [Neel, Victor] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Neel, V (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA. EM vneel@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD OCT PY 2015 VL 151 IS 10 BP 1057 EP 1058 DI 10.1001/jamadermatol.2015.0197 PG 2 WC Dermatology SC Dermatology GA CT6XF UT WOS:000362955700002 PM 25909594 ER PT J AU Peskind, ER Kraemer, B Zhang, J AF Peskind, Elaine R. Kraemer, Brian Zhang, Jing TI Biofluid Biomarkers of Mild Traumatic Brain Injury Whither Plasma Tau SO JAMA NEUROLOGY LA English DT Editorial Material ID CSF PHOSPHORYLATED TAU; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; BLOOD; DIAGNOSIS C1 [Peskind, Elaine R.] Vet Affairs NW Network Mental Illness Res Educ &, Seattle, WA USA. [Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98195 USA. [Kraemer, Brian] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Kraemer, Brian] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Sch Med, Seattle, WA 98195 USA. [Zhang, Jing] Univ Washington, Dept Pathol, Sch Med, Seattle, WA 98195 USA. RP Peskind, ER (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S ColumbianWay,S-116MIRECC, Seattle, WA 98108 USA. EM elaine.peskind@va.gov FU BLRD VA [I01 BX002619] NR 15 TC 1 Z9 1 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD OCT PY 2015 VL 72 IS 10 BP 1103 EP 1105 DI 10.1001/jamaneurol.2015.1789 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA CT6ZQ UT WOS:000362963000002 PM 26237033 ER PT J AU Salloway, S Sperling, R AF Salloway, Stephen Sperling, Reisa TI Understanding Conflicting Neuropathological Findings in Patients Clinically Diagnosed as Having Alzheimer Dementia SO JAMA NEUROLOGY LA English DT Editorial Material ID DISEASE; TRIALS C1 [Salloway, Stephen] Brown Univ, Alpert Med Sch, Dept Neurol, Providence, RI 02912 USA. [Salloway, Stephen] Brown Univ, Alpert Med Sch, Dept Psychiat, Providence, RI 02912 USA. [Sperling, Reisa] Butler Hosp, Dept Neurol, Providence, RI 02906 USA. [Sperling, Reisa] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Salloway, S (reprint author), Butler Hosp, Dept Neurol, 345 Blackstone Blvd, Providence, RI 02906 USA. EM ssalloway@butler.org NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD OCT PY 2015 VL 72 IS 10 BP 1106 EP 1108 DI 10.1001/jamaneurol.2015.1804 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA CT6ZQ UT WOS:000362963000004 PM 26302229 ER PT J AU Peeler, CE De Lott, LB Nagia, L Lemos, J Eggenberger, ER Cornblath, WT AF Peeler, Crandall E. De Lott, Lindsey B. Nagia, Lina Lemos, Joao Eggenberger, Eric R. Cornblath, Wayne T. TI Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis SO JAMA NEUROLOGY LA English DT Article ID GENERALIZED DISEASE; DIAGNOSTIC-VALUE AB IMPORTANCE The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocularmyasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. OBJECTIVES To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. DESIGN, SETTING, AND PARTICIPANTS A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. MAIN OUTCOMES AND MEASURES Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalizedmyasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. RESULTS Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% CI, 1.01-1.04; P = .007) and progression to generalizedmyasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26; P = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19-0.68; P = .002). Patients who developed symptoms of generalizedmyasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalizedmyasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = .002). CONCLUSIONS AND RELEVANCE We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the largest cohort of patients with OMG available to date. Older age, male sex, and progression to generalizedmyasthenia gravis were significantly associated with a positive antibody test result. In addition, to our knowledge, this is the first report of an association between high AChR antibody levels and progression from OMG to generalized disease. C1 [Peeler, Crandall E.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, Boston, MA 02114 USA. [Peeler, Crandall E.; De Lott, Lindsey B.; Cornblath, Wayne T.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Nagia, Lina; Lemos, Joao; Eggenberger, Eric R.] Michigan State Univ, Dept Neurol & Ophthalmol, E Lansing, MI 48824 USA. RP Peeler, CE (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, 243 Charles St, Boston, MA 02114 USA. EM crandall.peeler@gmail.com OI De Lott, Lindsey/0000-0003-2403-0207; Lemos, Joao/0000-0002-9128-7064 FU NEI NIH HHS [L30 EY025867]; NINDS NIH HHS [T32 NS007222] NR 17 TC 4 Z9 4 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD OCT PY 2015 VL 72 IS 10 BP 1170 EP 1174 DI 10.1001/jamaneurol.2015.1444 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA CT6ZQ UT WOS:000362963000013 PM 26258604 ER PT J AU Patel, AV Papakostas, TD Vavvas, DG AF Patel, Avni V. Papakostas, Thanos D. Vavvas, Demetrios G. TI Under the Guise of Retinitis SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID SYPHILITIC RETINITIS; OCULAR SYPHILIS; UVEITIS C1 [Patel, Avni V.; Papakostas, Thanos D.; Vavvas, Demetrios G.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Vavvas, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM vavvas@meei.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD OCT PY 2015 VL 133 IS 10 BP 1205 EP 1206 DI 10.1001/jamaophthalmol.2015.1926 PG 2 WC Ophthalmology SC Ophthalmology GA CT7AL UT WOS:000362965300023 PM 26226191 ER PT J AU van Zyl, T Papakostas, TD Sobrin, L AF van Zyl, Tave Papakostas, Thanos D. Sobrin, Lucia TI Vision Loss and Paresthesias in a Young Man SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID PLACOID PIGMENT EPITHELIOPATHY C1 [Sobrin, Lucia] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. [Sobrin, Lucia] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Uveitis Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Sobrin, L (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM lucia_sobrin@meei.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD OCT PY 2015 VL 133 IS 10 BP 1207 EP 1208 DI 10.1001/jamaophthalmol.2015.1935 PG 2 WC Ophthalmology SC Ophthalmology GA CT7AL UT WOS:000362965300024 PM 26270187 ER PT J AU Al-Moujahed, A Chodosh, J AF Al-Moujahed, Ahmad Chodosh, James TI Outcomes of an Algorithmic Approach to Treating Mild Ocular Alkali Burns SO JAMA OPHTHALMOLOGY LA English DT Letter C1 [Al-Moujahed, Ahmad; Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Chodosh, J (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu NR 4 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD OCT PY 2015 VL 133 IS 10 BP 1214 EP 1216 DI 10.1001/jamaophthalmol.2015.2302 PG 4 WC Ophthalmology SC Ophthalmology GA CT7AL UT WOS:000362965300027 PM 26226389 ER PT J AU Grzybowski, A Stacy, RC AF Grzybowski, Andrzej Stacy, Rebecca C. TI Temporal Artery Biopsy in Giant Cell Arteritis SO JAMA OPHTHALMOLOGY LA English DT Letter C1 [Grzybowski, Andrzej] Jozef Strus Poznan City Hosp, Dept Ophthalmol, PL-361285 Poznan, Poland. [Grzybowski, Andrzej] Univ Warmia & Mazury, Dept Ophthalmol, Olsztyn, Poland. [Stacy, Rebecca C.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Stacy, Rebecca C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Stacy, Rebecca C.] Novartis Inst BioMed Res, Cambridge, MA USA. RP Grzybowski, A (reprint author), Jozef Strus Poznan City Hosp, Dept Ophthalmol, 3 Szwajcarska St, PL-361285 Poznan, Poland. EM ae.grzybowski@gmail.com NR 4 TC 0 Z9 0 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD OCT PY 2015 VL 133 IS 10 BP 1220 EP 1220 DI 10.1001/jamaophthalmol.2015.2552 PG 1 WC Ophthalmology SC Ophthalmology GA CT7AL UT WOS:000362965300030 PM 26247876 ER PT J AU Tsai, AC Lucas, M Kawachi, I AF Tsai, Alexander C. Lucas, Michel Kawachi, Ichiro TI Association Between Social Integration and Suicide Among Women in the United States SO JAMA PSYCHIATRY LA English DT Article ID 3 PROSPECTIVE COHORTS; NATIONAL DEATH INDEX; SERVICES TASK-FORCE; BODY-MASS INDEX; PHYSICAL HEALTH; AMERICAN ADULTS; SEX-DIFFERENCES; NURSES HEALTH; MENTAL-HEALTH; PRIMARY-CARE AB IMPORTANCE Suicide is one of the top 10 leading causes of mortality among middle-aged women. Most work in the field emphasizes the psychiatric, psychological, or biological determinants of suicide. OBJECTIVE To estimate the association between social integration and suicide. DESIGN, SETTING, AND PARTICIPANTS We used data from the Nurses' Health Study, an ongoing nationwide prospective cohort study of nurses in the United States. Beginning in 1992, a population-based sample of 72 607 nurses 46 to 71 years of age were surveyed about their social relationships. The vital status of study participants was ascertained through June 1, 2010. EXPOSURES Social integration was measured with a 7-item index that included marital status, social network size, frequency of contact with social ties, and participation in religious or other social groups. MAIN OUTCOMES AND MEASURES The primary outcome of interestwas suicide, defined as deaths classified using the codes E950 to E959 from the International Classification of Diseases, Eighth Revision. RESULTS During more than 1.2 million person-years of follow-up (1992-2010), there were 43 suicide events. The incidence of suicide decreased with increasing social integration. In a multivariable Cox proportional hazards regression model, the relative hazard of suicide was lowest among participants in the highest category of social integration (adjusted hazard ratio, 0.23 [95% CI, 0.09-0.58]) and second-highest category of social integration (adjusted hazard ratio, 0.26 [95% CI, 0.09-0.74]). Increasing or consistently high levels of social integration were associated with a lower risk of suicide. These findings were robust to sensitivity analyses that accounted for poor mental health and serious physical illness. CONCLUSIONS AND RELEVANCE Women who were socially well integrated had a more than 3-fold lower risk for suicide over 18 years of follow-up. C1 [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Ctr Populat & Dev Studies, Cambridge, MA USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Lucas, Michel] Univ Laval, Dept Social & Prevent Med, Quebec City, PQ, Canada. [Lucas, Michel] Ctr Hosp Univ Quebec, Res Ctr, Populat Hlth & Optimal Hlth Practices Res Unit, Quebec City, PQ, Canada. [Lucas, Michel] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kawachi, Ichiro] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Kawachi, Ichiro] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU US National Institutes of Health [UM1 CA186107]; Robert Wood Johnson Foundation Health and Society Scholars Program; National Institutes of Health [K23MH096620] FX The Nurses' Health Study was funded by the US National Institutes of Health (grant UM1 CA186107). This analysis was also supported through a seed grant from the Robert Wood Johnson Foundation Health and Society Scholars Program. The authors acknowledge salary support from the National Institutes of Health (grant K23MH096620) and the Robert Wood Johnson Foundation Health and Society Scholars Program. NR 87 TC 7 Z9 7 U1 4 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD OCT PY 2015 VL 72 IS 10 BP 987 EP 993 DI 10.1001/jamapsychiatry.2015.1002 PG 7 WC Psychiatry SC Psychiatry GA CT7CW UT WOS:000362972000010 PM 26222043 ER PT J AU Visness, CM Sandel, MT O'Connor, G Gern, JE Jaffee, KF Wood, RA Kattan, M Bloomberg, GR Dresen, A Gergen, PJ Gold, DR Lemanske, RF Rajamanickam, V Camargo, CA Jackson, DJ AF Visness, Cynthia M. Sandel, Megan T. O'Connor, George Gern, James E. Jaffee, Katy F. Wood, Robert A. Kattan, Meyer Bloomberg, Gordon R. Dresen, Amy Gergen, Peter J. Gold, Diane R. Lemanske, Robert F. Rajamanickam, Victoria Camargo, Carlos A. Jackson, Daniel J. TI Cord blood vitamin D concentrations are unrelated to atopy and wheeze in 2 diverse birth cohort studies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID 25-HYDROXYVITAMIN D LEVELS; ASTHMA; SENSITIZATION; PREGNANCY; CHILDREN; RISK C1 [Visness, Cynthia M.; Jaffee, Katy F.] Rho Fed Syst Div Inc, Chapel Hill, NC 27515 USA. [Sandel, Megan T.; O'Connor, George] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gern, James E.; Dresen, Amy; Lemanske, Robert F.; Rajamanickam, Victoria; Jackson, Daniel J.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kattan, Meyer] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Bloomberg, Gordon R.] Washington Univ, Sch Med, St Louis, MO USA. [Gergen, Peter J.] NIH, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. [Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Camargo, Carlos A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Visness, CM (reprint author), Rho Fed Syst Div Inc, Chapel Hill, NC 27515 USA. EM djj@medicine.wisc.edu FU NCATS NIH HHS [UL1 TR000427, UL1 TR000448]; NCRR NIH HHS [M01 RR000052, UL1 RR025771, RR00052, M01RR00533, M01 RR000533, UL1 RR024156, M01 RR03186, M01 RR003186, M01 RR000071, UL1 RR024992, 1UL1RR025771, 1UL1RR024156, M01RR00071, 5UL1RR024992-02]; NHLBI NIH HHS [R01 HL61879, P01 HL070831, P01 HL70831]; NIAID NIH HHS [UM1 AI114271, N01-AI-25482, HHSN272200900052C, N01AI25482, N01-AI-25496, N01AI25496, HHSN272201000052I]; NICHD NIH HHS [R01 HD061879]; NIMH NIH HHS [R01 MH061879]; PHS HHS [HHSN272200900052C, HHSN272201000052I] NR 11 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2015 VL 136 IS 4 BP 1108 EP 1110 DI 10.1016/j.jaci.2015.03.046 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA CT7EJ UT WOS:000362976300035 PM 25979524 ER PT J AU Lai, PS Liang, LM Cibas, ES Liu, AH Gold, DR Baccarelli, A Phipatanakul, W AF Lai, Peggy S. Liang, Liming Cibas, Edmund S. Liu, Andrew H. Gold, Diane R. Baccarelli, Andrea Phipatanakul, Wanda TI Alternate methods of nasal epithelial cell sampling for airway genomic studies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID CHILDHOOD ASTHMA; GENE-EXPRESSION C1 [Lai, Peggy S.] Massachusetts Gen Hosp, Div Pulm & Crit Care, Boston, MA 02114 USA. [Lai, Peggy S.; Gold, Diane R.; Baccarelli, Andrea] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Liang, Liming] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lai, Peggy S.; Cibas, Edmund S.; Gold, Diane R.; Phipatanakul, Wanda] Harvard Univ, Boston, MA USA. [Cibas, Edmund S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Liu, Andrew H.] Natl Jewish Hlth, Pediat Allergy & Immunol, Denver, CO USA. [Liu, Andrew H.] Univ Colorado, Sch Med, Denver, CO USA. [Phipatanakul, Wanda] Boston Childrens Hosp, Allergy & Immunol, Boston, MA USA. RP Lai, PS (reprint author), Massachusetts Gen Hosp, Div Pulm & Crit Care, Boston, MA 02114 USA. EM wanda.phipatanakul@childrens.harvard.edu OI Lai, Peggy/0000-0001-9501-8606; Baccarelli, Andrea/0000-0002-3436-0640 FU NCATS NIH HHS [UL1 TR001102]; NHLBI NIH HHS [U10 HL098102, U10HL098102]; NIAID NIH HHS [U01 AI110397, K24 AI 106822, K24 AI106822, R01 AI073964, R01 AI 073964]; NIEHS NIH HHS [K23ES023700, P30 ES000002, P30ES000002, P01 ES018181, K23 ES023700, P01ES018181] NR 8 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2015 VL 136 IS 4 BP 1120 EP 1123 DI 10.1016/j.jaci.2015.04.032 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA CT7EJ UT WOS:000362976300041 PM 26037550 ER PT J AU Calderwood, S Collier, TL Gouverneur, V Liang, SH Vasdev, N AF Calderwood, Samuel Collier, Thomas Lee Gouverneur, Veronique Liang, Steven H. Vasdev, Neil TI Synthesis of F-18-arenes from spirocyclic iodonium(III) ylides via continuous-flow microfluidics SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE Fluorine-18; Iodonium(III) ylide; [F-18]FPEB; 4-[F-18]Fluorobenzyl azide; PET; F-18 ID PET RADIOTRACER; CHEMISTRY; TRACER; METABOTROPIC-GLUTAMATE-RECEPTOR-SUBTYPE-5; RADIOFLUORINATION; RADIOSYNTHESIS; RECEPTORS; F-18-FPEB; F-18 AB Spirocyclic hypervalent iodine(III)ylidesthave proven to be synthetically versatile precursors for efficient radiolabelling of a diverse range of non-activated (hetero)arenes, highly functionalised small molecules, building blocks and radippharmaceuticals from [F-18]fluoride ion. Herein, we report the implementation of these reactions onto a continuous-flow microfluidic platform, thereby offering an alterative and automated synthetic procedure of a radiopharmaceutical, 3-[F-18]fluoro-5-[(pyridin-3-yl)ethynyllbenzonitrile ([F-18]FPEB) and a routinely used building block for click-radiochemistry, 4-[F-18]fluorobenzyl azide. This new protocol was applied to the synthesis of [F-18]FPEB (radiochemical conversion (RCC) = 68 +/- 5%) and 4-[F-18]fluorobenzyl azide (RCC = 68 +/- 5%; isolated radiochemical yield = 24 +/- 0%). We anticipate that the high throughput microfluidic platform will accelerate the discovery and applications of F-18-labelled building blocks and labelled compounds prepared by iodonium ylide precursors as well as the production of radiotracers for preclinical imaging studies. (C) 2015 Elsevier B.V. All rights reserved. C1 [Calderwood, Samuel; Gouverneur, Veronique] Univ Oxford, Chem Res Lab, Oxford, England. [Calderwood, Samuel; Collier, Thomas Lee; Liang, Steven H.; Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Collier, Thomas Lee; Liang, Steven H.; Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Collier, Thomas Lee] Advion BioSyst, Ithaca, NY USA. RP Liang, SH (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA. EM liang.steven@mgh.harvard.edu; vasdev.neil@mgh.harvard.edu FU MRC; Ground Fluor Pharmaceuticals; Royal Society Wolfson Research Merit Award FX Financial support was provided by the MRC (SC), Advion (SC & NV) and Ground Fluor Pharmaceuticals (NV). VG holds a Royal Society Wolfson Research Merit Award (2013-2018). We thank Dr. Benjamin H. Rotstein and Dr. Nickeisha Stephenson foe selected substrate synthesis and helpful discussions. We thank Dr Jack A. Correia, David F. Lee, Jr. and Tim Beaudoin and the Massachusetts General Hospital PET Core facility for 18F-fluoride production NR 23 TC 5 Z9 5 U1 5 U2 15 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 EI 1873-3328 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD OCT PY 2015 VL 178 BP 249 EP 253 DI 10.1016/j.jfluchem.2015.08.006 PG 5 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA CT6NL UT WOS:000362929600035 PM 27512233 ER PT J AU Fisher, LB Fava, M Doros, GD Alpert, JE Henry, M Huz, I Freeman, MP AF Fisher, Lauren B. Fava, Maurizio Doros, Gheorghe D. Alpert, Jonathan E. Henry, Michael Huz, Ilana Freeman, Marlene P. TI The Role of Anger/Hostility in Treatment-Resistant Depression A Secondary Analysis From the ADAPT-A Study SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Anger; hostility; treatment-resistant depression; augmentation ID CHRONIC MAJOR DEPRESSION; ANGER ATTACKS; DOUBLE-BLIND; TREATMENT RESPONSE; CLINICAL-TRIALS; ANTIDEPRESSANT TREATMENT; SYMPTOM QUESTIONNAIRE; UNIPOLAR DEPRESSION; INADEQUATE-RESPONSE; ADJUNCTIVE THERAPY AB Major depressive disorder is often accompanied by elevated levels of anger, hostility, and irritability, which may contribute to worse outcomes. The present study is a secondary analysis examining the role of anger/hostility in the treatment response to low-dose aripiprazole added to antidepressant therapy in 225 patients with major depressive disorder and inadequate response to antidepressant treatment. Repeated-measures model demonstrated no drug-placebo difference in treatment response across levels of anger/hostility. However, within-group analyses showed significantly lower placebo response rates in patients with high anger/hostility and a trend for lower drug response rates in patients with high anger/hostility. Pooled response rates across phases and treatments revealed a lower response rate among patients with high anger/hostility. Depressed patients with high anger/hostility demonstrate greater illness severity and lower depressive treatment response rates than patients with low anger/hostility, suggesting that patients with high anger/hostility may have poorer outcomes in response to adjunctive treatment. C1 [Fisher, Lauren B.; Alpert, Jonathan E.; Huz, Ilana] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Fisher, Lauren B.; Fava, Maurizio; Freeman, Marlene P.] Massachusetts Gen Hosp, Clin Trials & Network Inst, Boston, MA 02114 USA. [Doros, Gheorghe D.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Henry, Michael] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Henry, Michael] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. RP Fisher, LB (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM lbfisher@mgh.harvard.edu OI Alpert, Jonathan/0000-0002-4332-908X FU Bristol-Myers Squibb FX The ADAPT-A Study was an investigator-initiated study supported by Bristol-Myers Squibb, which also provided blinded study medication. NR 44 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 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 2015 VL 203 IS 10 BP 762 EP 768 DI 10.1097/NMD.0000000000000364 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CT3LU UT WOS:000362709000005 PM 26348584 ER PT J AU Cassano, P Trinh, NH Chang, T Cusin, C Fisher, L Pedrelli, P Nyer, M Kim, DJH Alpert, J Mischoulon, D AF Cassano, Paolo Trinh, Nhi-Ha Chang, Trina Cusin, Cristina Fisher, Lauren Pedrelli, Paola Nyer, Maren Kim, Daniel Ju Hyung Alpert, Jonathan Mischoulon, David TI Treatment Outcome in Depressed Latinos Predicted by Concomitant Psychosislike Symptoms SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Psychosislike symptoms; Latinos; antipsychotic augmentation; major depressive disorder; psychotic spectrum; subthreshold psychosis ID PSYCHOTIC SYMPTOMS; DISORDER AB We compared treatment response (50 decrease in Nine-Item Patient Health Questionnaire total score) among 24 Latinos with major depressive disorder, presenting with and without specific psychosislike symptoms: A, hearing noises or house sounds, B, hearing voices calling one's name, C, seeing fleeting visions such as shadows, and D, symptoms more likely to be truly psychotic (e.g., poorly defined and short-lasting voices [other than B], fleeting paranoid ideation, or fleeting ideas of reference). 18 subjects (75%) endorsed symptoms of cluster A, 12 (50%) of cluster B, 10 (31%) of cluster C, and 12 (50%) of cluster D. Only subjects who reported symptoms from the D cluster exhibited significantly unfavorable depressive outcomes (compared to those with absence of D symptoms). The authors propose a phenomenological differentiation between benign psychosislike symptoms (clusters A-C) and the expression of the psychotic continuum (cluster D) in depressed Latinos. C1 [Cassano, Paolo; Trinh, Nhi-Ha; Chang, Trina; Cusin, Cristina; Fisher, Lauren; Pedrelli, Paola; Nyer, Maren; Kim, Daniel Ju Hyung; Alpert, Jonathan; Mischoulon, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Cassano, Paolo] North Suffolk Mental Hlth Assoc, Chelsea, MA USA. RP Cassano, P (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM pcassano@mgh.harvard.edu OI Alpert, Jonathan/0000-0002-4332-908X FU Photothera Inc.; Brain and Behavior Research Foundation; Abbott Laboratories; Alkermes; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Aspect Medical Systems; AstraZeneca; Bristol-Myers Squibb Company; Cephalon; Cyberonics; Eli Lilly Company; Forest Pharmaceuticals Inc.; GlaxoSmithKline; J & J Pharmaceuticals; Novartis; Organon Inc.; PamLab, LLC; Pfizer Inc; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories; Belvoir Publishing; Bowman Family Foundation; Fisher Wallace; Nordic Naturals; Methylation Sciences, Inc. (MSI); PharmoRx Therapeutics FX Dr. Cassano: Research support from Photothera Inc. and from Brain and Behavior Research Foundation. Drug donation was from TEVA. Travel reimbursement from Pharmacia-Upjohn and from Brain and Behavior Research Foundation.; Dr. Alpert: Dr. Alpert has received research support from: Abbott Laboratories, Alkermes, Lichtwer Pharma GmbH, Lorex Pharmaceuticals; Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb Company, Cephalon, Cyberonics, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, J & J Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, Inc., and Wyeth-Ayerst Laboratories. Dr. Alpert has participated on advisory boards for or consulted to Eli Lilly & Company, Pamlab LLC, and Pharmavite LLC.; Dr. Alpert has received speakers' honoraria from: Eli Lilly & Company, Xian-Janssen, Organon, MGH Psychiatry Academy, Reed Medical Education, Primedia, the Nevada Psychiatric Association, and the American Psychiatric Association and has received editorial fees from Belvoir Publishing.; Dr. Mischoulon, June 2013 to May 2014: Dr. Mischoulon has received research support from the Bowman Family Foundation, Fisher Wallace, Nordic Naturals, Methylation Sciences, Inc. (MSI), and PharmoRx Therapeutics. Dr. Mischoulon has received honoraria for consulting, speaking, and writing from Pamlab, and the Massachusetts General Hospital Psychiatry Academy. Dr. Mischoulon has received royalties from Lippincott Williams & Wilkins for published book Natural Medications for Psychiatric Disorders: Considering the Alternatives. NR 14 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 2015 VL 203 IS 10 BP 769 EP 773 DI 10.1097/NMD.0000000000000365 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CT3LU UT WOS:000362709000006 PM 26356091 ER PT J AU Hayden, EY Yamin, G Beroukhim, S Chen, B Kibalchenko, M Jiang, L Ho, L Wang, J Pasinetti, GM Teplow, DB AF Hayden, Eric Y. Yamin, Ghiam Beroukhim, Shiela Chen, Benson Kibalchenko, Mikhail Jiang, Lin Ho, Lap Wang, Jun Pasinetti, Giulio M. Teplow, David B. TI Inhibiting amyloid -protein assembly: Size-activity relationships among grape seed-derived polyphenols SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; amyloid -protein (A); grape seeds; inhibitors; oligomers; polyphenols ID SMALL MOLECULE DOCKING; BETA-PROTEIN; ALZHEIMERS-DISEASE; WINE CONSUMPTION; CROSS-LINKING; EADOCK DSS; DEMENTIA; EXTRACT; FIBRILLOGENESIS; OLIGOMERIZATION AB Epidemiological evidence that red wine consumption negatively correlates with risk of Alzheimer's disease has led to experimental studies demonstrating that grape seed extracts inhibit the aggregation and oligomerization of A invitro and ameliorate neuropathology and behavioral deficits in a mouse model of Alzheimer's disease. The active agent in the extracts is a mixed population of polyphenolic compounds. To evaluate the relative potency of each of these compounds, HPLC was used to fractionate the mixture into monomers, dimers, and oligomers. Each fraction was analyzed for its effect on A conformational dynamics (circular dichroism), oligomerization (zero-length photochemical cross-linking), aggregation kinetics (Thioflavin T fluorescence), and morphology (electron microscopy). The relative activities of each fraction were determined on the basis of molar concentration (mol/L) or mass concentration (g/L). When molar concentration, the number concentration of each polyphenolic compound, was considered, the oligomer fraction was the most potent inhibitor of A oligomerization and aggregation. However, when mass concentration, the number concentration of phenolic groups, was considered, monomers were the most potent inhibitors. To understand these ostensibly contradictory results, a model of polyphenol:A complexation was developed. This model, which was found to be consistent with published X-ray crystallographic studies, offers an explanation for the effects of functional group polyvalency on inhibitor activity. Our data emphasize the importance of an in-depth understanding of the mechanism(s) underlying concentration dependence' in inhibitor systems involving polyfunctional agents. C1 [Hayden, Eric Y.; Yamin, Ghiam; Beroukhim, Shiela; Chen, Benson; Kibalchenko, Mikhail; Jiang, Lin; Teplow, David B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Yamin, Ghiam] Univ Calif Los Angeles, Neurosci Interdept Ph Program, Med Sci Training Program, Los Angeles, CA 90095 USA. [Ho, Lap; Wang, Jun; Pasinetti, Giulio M.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Ho, Lap; Wang, Jun; Pasinetti, Giulio M.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Wang, Jun; Pasinetti, Giulio M.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Wang, Jun; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. [Teplow, David B.] Univ Calif Los Angeles, David Geffen Sch Med, MBI, Los Angeles, CA 90095 USA. [Teplow, David B.] Univ Calif Los Angeles, David Geffen Sch Med, BRI, Los Angeles, CA 90095 USA. RP Teplow, DB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, 635 Charles E Young Dr S,Room 445, Los Angeles, CA 90095 USA. EM dteplow@mednet.ucla.edu FU UCLA Chemistry-Biology Interface (CBI) Training Program; UCLA Training Program in Neural Repair; Jim Easton Consortium for Alzheimer's Drug Discovery, and Biomarkers at UCLA; NIH [AG027818, NS038328, AG041295]; NCCIH Center [1PO1AT004511-031] FX We thank Dr. Zhefeng Gou for helpful discussions. This work was supported by grants from the UCLA Chemistry-Biology Interface (CBI) Training Program, UCLA Training Program in Neural Repair, Jim Easton Consortium for Alzheimer's Drug Discovery, and Biomarkers at UCLA, and NIH grants AG027818, NS038328, and AG041295. This study was supported in part through support from the NCCIH Center Grant 1PO1AT004511-031 to GMP. Dr. Pasinetti holds a Career Scientist Award in the Research and Development unit and is the Director of the Basic and Biomedical Research and Training Program, GRECC, James J. Peters Veterans Affairs Medical Center. We acknowledge that the contents of this article do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Drs. Pasinetti, Wang, and Ho are named inventors on a patent filed through the Icahn School of Medicine at Mount Sinai for the use of grape seed extract for the treatment of Alzheimer's disease and other neurodegenerative disorders. Drs Pasinetti, Wang, and Ho are entitled to receive royalties from this invention. NR 44 TC 2 Z9 2 U1 7 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2015 VL 135 IS 2 BP 416 EP 430 DI 10.1111/jnc.13270 PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CT5DP UT WOS:000362828200019 PM 26228682 ER PT J AU Roiland, RA Lin, F Phelan, C Chapman, BP AF Roiland, R. A. Lin, F. Phelan, C. Chapman, B. P. TI Stress regulation as a link between executive function and pre-frailty in older adults SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article DE Pre-frailty; executive function; stress regulation ID HEART-RATE-VARIABILITY; POOR COGNITIVE PERFORMANCE; SLEEP QUALITY; WOMENS HEALTH; INFLAMMATION; AGE; ATTENTION; INDEXES; SAMPLE; ASSOCIATION AB Both pre-frailty and frailty are linked with impaired executive function (EF) but the mechanism underlying this relationship is not known. Williams and colleagues' model posits EF affects health outcomes via stress regulation. This model was utlized to test indicators of stress regulation as mediators of the relationship between EF and pre-frailty in older adults. Cross-sectional. Academic general clinical research centers. 690 community-dwelling older adults a parts per thousand yen 50 years of age. Pre-frailty was measured using a modified form of the Fried Frailty measure. EF was assessed via telephone-based neurocognitive assessments. Indicators of stress regulation included: stress exposure (measured by perceived stress), reactivity and recovery (measured by heart rate) and restoration (measured by serum interleukin-6 and sleep quality). 396 individuals were classified as non-frail, 277 as pre-frail, and 17 as frail. Pre-frail and non-frail individuals were included in data analyses. Compared to non-frail individuals, pre-frail were older and exhibited poorer EF, higher levels of stress exposure and poorer stress restoration. Poorer EF was associated with greater stress exposure, less stress reactivity, longer stress recovery and poorer stress restoration. The total effect of the relationship between EF and pre-frailty was significant with significant indirect effects supporting stress exposure and restoration as mediators of the relationship. Stress exposure and restoration appear to mediate the relationship between EF and pre-frailty. Longitudinal studies are needed to clarify the direction of causality and determine whether stress regulation processes are appropriate targets for interventions aiming to prevent declines in EF and the development of pre-frailty. C1 [Roiland, R. A.; Phelan, C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr 11 G, Madison, WI 53705 USA. [Lin, F.] Univ Rochester, Sch Nursing, Rochester, NY 14627 USA. [Chapman, B. P.] Univ Rochester, Dept Psychiat, Rochester, NY 14627 USA. RP Roiland, RA (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr 11 G, Madison, WI 53705 USA. EM rachel.roiland@va.gov FU U.S. Department of Veterans Affairs, Biomedical Laboratory Research & Development Program [IK2 CX000535] FX This manuscript was partially prepared during postdoctoral training (RR) at the William S. Middleton Veterans Affairs Hospital in Madison, WI; GRECC manuscript 003. This work was also supported by Career Development Award #IK2 CX000535 (CP) from the U.S. Department of Veterans Affairs, Biomedical Laboratory Research & Development Program. The views and content expressed in this article are soley the responsibility of the authors and do not necessarily reflect the position, policy, or official views of the Department of Veterans Affairs, U.S. government, or the National Institutes of Health. NR 54 TC 1 Z9 1 U1 2 U2 5 PU SPRINGER FRANCE PI PARIS PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE SN 1279-7707 EI 1760-4788 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD OCT PY 2015 VL 19 IS 8 BP 828 EP 838 DI 10.1007/s12603-015-0476-1 PG 11 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA CT3CL UT WOS:000362683900005 PM 26412287 ER PT J AU Gunn, AJ Mangano, M Choy, G Sahani, DV Boland, GW AF Gunn, Andrew J. Mangano, Mark Choy, Garry Sahani, Dushyant V. Boland, Giles W. TI Re: "Patients Prefer Results From the Ordering Provider and Access to Their Radiology Reports" SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Letter C1 [Gunn, Andrew J.] Washington Univ, Mallinckrodt Inst Radiol, Sch Med St Louis, St Louis, MO 63130 USA. [Mangano, Mark; Choy, Garry; Sahani, Dushyant V.; Boland, Giles W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Gunn, AJ (reprint author), Washington Univ, Mallinckrodt Inst Radiol, Sch Med St Louis, St Louis, MO 63130 USA. EM gunna@mir.wustl.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD OCT PY 2015 VL 12 IS 10 BP 1006 EP 1006 AR S1546-14400(15)00556-6 DI 10.1016/j.jacr.2015.06.023 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT6MX UT WOS:000362928200003 PM 26435112 ER PT J AU Harvey, HB Wu, CC Gilman, MD Vartanians, V Halpern, EF Pandharipande, PV Shepard, JO Alkasab, TK AF Harvey, H. Benjamin Wu, Carol C. Gilman, Matthew D. Vartanians, Vartan Halpern, Elkan F. Pandharipande, Pari V. Shepard, Joanne O. Alkasab, Tarik K. TI Correlation of the Strength of Recommendations for Additional Imaging to Adherence Rate and Diagnostic Yield SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Recommendation; strength; radiology reporting; adherence; diagnostic yield ID REFERRING PHYSICIAN; FOLLOW-UP; CHEST CT; RADIOLOGY; COMMUNICATION AB Purpose: The aim of this study was to evaluate the association between the wording of radiologist recommendations for chest CT with the likelihood of recommendation adherence and the diagnostic yield of the recommended follow-up CT imaging. Methods: This HIPAA-compliant retrospective study had institutional review board approval, including waiver of the requirement for patient consent. All outpatient chest radiographic (CXR) studies performed at a tertiary care academic medical center in 2008 (n = 29,138) were searched to identify examinations with recommendations for chest CT. The wording of chest CT recommendations was classified as conditional or absolute, on the basis of whether the recommendation stood independent of the clinical judgment of the ordering clinician. Using the radiology information system, patients who underwent chest CT within 90 days of the index CXR study containing the recommendation were determined, and the CT studies were evaluated to determine if there were abnormalities corresponding to the CXR abnormalities that prompted the recommendations. Corresponding abnormalities were categorized as clinically relevant or not, on the basis of whether further workup or treatment was warranted. Groups were compared using t tests and Fisher exact tests. Results: Recommendations for chest CT appeared in 4.5% of outpatient CXR studies (1,316 of 29,138; 95% confidence interval [CI], 4.3%-4.8%); 39.4% (519 of 1,316; 95% CI, 36.8%-42.0%) were conditional and 60.6% (797 of 1,316; 95% CI, 58.0%-63.2%) were absolute. Patients with absolute recommendations were significantly more likely to undergo follow-up chest CT within 90 days than patients with conditional recommendations (67.8% vs 45.8%, respectively, P < .001). Despite this difference in provider adherence, there was no significant difference between the conditional and absolute recommendation groups with regard to the incidence of clinically relevant corresponding findings (P = .16) or malignancy (P = .08) on follow-up CT. Conclusions: Conditional radiologist recommendations are associated with decreased provider adherence, though the likelihood of a clinically relevant finding on follow-up CT is no different than with absolute recommendations. C1 [Harvey, H. Benjamin; Wu, Carol C.; Gilman, Matthew D.; Halpern, Elkan F.; Pandharipande, Pari V.; Shepard, Joanne O.; Alkasab, Tarik K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Harvey, H. Benjamin; Wu, Carol C.; Gilman, Matthew D.; Halpern, Elkan F.; Pandharipande, Pari V.; Shepard, Joanne O.; Alkasab, Tarik K.] Harvard Univ, Sch Med, Boston, MA USA. [Halpern, Elkan F.; Pandharipande, Pari V.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Vartanians, Vartan] Lahey Hosp & Med Ctr, Burlington, MA USA. RP Harvey, HB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM hbharvey@partners.org NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD OCT PY 2015 VL 12 IS 10 BP 1016 EP 1022 DI 10.1016/j.jacr.2015.03.038 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT6MX UT WOS:000362928200011 PM 26092592 ER PT J AU Pianykh, OS Rosenthal, DI AF Pianykh, Oleg S. Rosenthal, Daniel I. TI Can We Predict Patient Wait Time? SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Queueing Theory; Hospital Information System; time series; predictive models; regression ID DISCRETE-EVENT SIMULATION; EMERGENCY-DEPARTMENT; CARE; SATISFACTION AB Purpose: The importance of patient wait-time management and predictability can hardly be overestimated: For most hospitals, it is the patient queues that drive and define every bit of clinical workflow. The objective of this work was to study the predictability of patient wait time and identify its most influential predictors. Methods: To solve this problem, we developed a comprehensive list of 25 wait-related parameters, suggested in earlier work and observed in our own experiments. All parameters were chosen as derivable from a typical Hospital Information System dataset. The parameters were fed into several time-predicting models, and the best parameter subsets, discovered through exhaustive model search, were applied to a large sample of actual patient wait data. Results: We were able to discover the most efficient wait-time prediction factors and models, such as the line-size models introduced in this work. Moreover, these models proved to be equally accurate and computationally efficient. Finally, the selected models were implemented in our patient waiting areas, displaying predicted wait times on the monitors located at the front desks. The limitations of these models are also discussed. Conclusions: Optimal regression models based on wait-line sizes can provide accurate and efficient predictions for patient wait time. C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Pianykh, OS (reprint author), Harvard Univ, Sch Med, Off 470, 25 New Chardon St, Boston, MA 02114 USA. EM opianykh@mgh.harvard.edu RI Pianykh, Oleg/N-2456-2015 OI Pianykh, Oleg/0000-0002-9107-5432 NR 20 TC 0 Z9 0 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD OCT PY 2015 VL 12 IS 10 BP 1058 EP 1066 DI 10.1016/j.jacr.2015.04.010 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT6MX UT WOS:000362928200017 PM 26435119 ER PT J AU Boland, GW Duszak, R AF Boland, Giles W. Duszak, Richard, Jr. TI Modality Access: Strategies for Optimizing Throughput SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Boland, Giles W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Atlanta, GA USA. RP Boland, GW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD OCT PY 2015 VL 12 IS 10 BP 1073 EP 1075 DI 10.1016/j.jacr.2015.06.012 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT6MX UT WOS:000362928200020 PM 26435120 ER PT J AU Thrall, JH AF Thrall, James H. TI Moreton Lecture: Imaging in the Age of Precision Medicine SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Precision medicine; radiogenomics; imaging phenotype; genotype; mutation ID STAGE HODGKINS LYMPHOMA; SPOT SIGN SCORE; INTRACEREBRAL HEMORRHAGE; CLINICAL-TRIALS; TUMOR; NEUROFIBROMATOSIS; CANCER; RADIOGENOMICS; VALIDATION; BIOMARKERS AB The term "precision medicine" (also known as "personalized medicine") is broadly defined as the tailoring of medical treatment to the individual characteristics of each patient. This process entails classifying patients into subpopulations that differ in their susceptibility to a particular disease, in the biology and/or prognosis of those diseases they may develop, or in their response to a specific treatment. Subpopulations are defined through systematic analysis and classification of patients' genotypic and phenotypic characteristics. Image findings are surrogates for phenotype manifestation of disease, and radiology reports are written descriptions of imaging phenotypes. Imaging phenotypes are often presented as classification, grading, or scoring systems that help assign patients to subpopulations for selecting treatment or assessing prognosis. The "spot sign score" that reflects the severity of bleeding in intracerebral hemorrhage is an example that has been used as an inclusion criterion in clinical trials. The term "radiogenomics" is used to describe the study of linkage between a patient's genotype and imaging phenotype. When a, patient's genotype is known, it often suggests a surveillance role for imaging to determine clinical occurrence, location, extent, and severity of the associated disease; for example, use of breast imaging for enhanced surveillance in women known to harbor the BRCA1 and BRCA2 genes. Imaging is poised to play major roles in the age of precision medicine. The imaging community needs to learn new terminology and think in terms of how imaging phenotypes and imaging surveillance of patients with known genetic mutations can contribute to the, concept. Copyright (C) 2015 American College of Radiology C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Rm 216,32 Fruit St, Boston, MA 02114 USA. EM jthrall@partners.org NR 28 TC 2 Z9 2 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD OCT PY 2015 VL 12 IS 10 BP 1106 EP 1111 DI 10.1016/j.jacr.2015.06.003 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT6MX UT WOS:000362928200028 PM 26303360 ER PT J AU Hricak, H Ringertz, HG Thrall, JH Dixon, AK Arenson, RL Bradley, WG Muellner, A Krestin, GP AF Hricak, Hedvig Ringertz, Hans G. Thrall, James H. Dixon, Adrian K. Arenson, Ronald L. Bradley, William G. Muellner, Ada Krestin, Gabriel P. TI When Vision Prevails: A History of the International Society for Strategic Studies in Radiology SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Hricak, Hedvig; Muellner, Ada] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Ringertz, Hans G.] Linkoping Univ Hosp, Ctr Med Image Sci & Visualizat, S-58185 Linkoping, Sweden. [Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Dixon, Adrian K.] Addenbrookes Hosp, Dept Radiol, Cambridge CB2 2QQ, England. [Arenson, Ronald L.] Univ Calif San Francisco, Sch Med, Dept Radiol, San Francisco, CA 94143 USA. [Bradley, William G.] Univ Calif San Diego, Med Ctr, Dept Radiol, San Diego, CA 92103 USA. [Krestin, Gabriel P.] Univ Rotterdam Hosp, Dept Radiol, Rotterdam, Netherlands. RP Hricak, H (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave,Room C-276, New York, NY 10065 USA. NR 7 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD OCT PY 2015 VL 12 IS 10 BP 1112 EP 1114 DI 10.1016/j.jacr.2015.06.007 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT6MX UT WOS:000362928200029 PM 26116068 ER PT J AU Hubbard, BP Badran, AH Zuris, JA Guilinger, JP Davis, KM Chen, LW Tsai, SQ Sander, JD Joung, JK Liu, DR AF Hubbard, Basil P. Badran, Ahmed H. Zuris, John A. Guilinger, John P. Davis, Kevin M. Chen, Liwei Tsai, Shengdar Q. Sander, Jeffry D. Joung, J. Keith Liu, David R. TI Continuous directed evolution of DNA-binding proteins to improve TALEN specificity SO NATURE METHODS LA English DT Article ID ZINC FINGERS; RECOGNITION; EFFECTORS; NUCLEASES; SELECTION; SYSTEM; PHAGE; CELLS; CODE AB Nucleases containing programmable DNA-binding domains can alter the genomes of model organisms and have the potential to become human therapeutics. Here we present DNA-binding phage-assisted continuous evolution (DB-PACE) as a general approach for the laboratory evolution of DNA-binding activity and specificity. We used this system to generate transcription activator-like effectors nucleases (TALENs) with broadly improved DNA cleavage specificity, establishing DB-PACE as a versatile approach for improving the accuracy of genome-editing agents. C1 [Hubbard, Basil P.; Badran, Ahmed H.; Zuris, John A.; Guilinger, John P.; Davis, Kevin M.; Chen, Liwei; Liu, David R.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Liu, DR (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. EM drliu@fas.harvard.edu FU Defense Advanced Research Projects Agency (DARPA) [HR0011-11-2-0003, DARPA N66001-12-C-4207]; US National Institutes of Health (NIH)/NIGMS [R01 GM095501, R01 GM065400]; Howard Hughes Medical Institute; NIH Director's Pioneer Award [DP1 GM105378]; NIH [F32 GM105189]; Harvard Chemical Biology Program; US National Science Foundation Graduate Research Fellowship FX This work was supported by Defense Advanced Research Projects Agency (DARPA) HR0011-11-2-0003, DARPA N66001-12-C-4207, a grant from the US National Institutes of Health (NIH)/NIGMS (R01 GM095501 and R01 GM065400) and the Howard Hughes Medical Institute. S.Q.T., J.D.S. and J.K.J. were supported by an NIH Director's Pioneer Award (DP1 GM105378). S.Q.T. was supported by NIH F32 GM105189. A.H.B. was supported by the Harvard Chemical Biology Program and a US National Science Foundation Graduate Research Fellowship. NR 19 TC 11 Z9 11 U1 7 U2 38 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD OCT PY 2015 VL 12 IS 10 BP 939 EP 942 DI 10.1038/NMETH.3515 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CT3IE UT WOS:000362699600021 PM 26258293 ER PT J AU Leffler, DA Green, PHR Fasano, A AF Leffler, Daniel A. Green, Peter H. R. Fasano, Alessio TI Extraintestinal manifestations of coeliac disease SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Review ID GLUTEN-FREE DIET; IRON-DEFICIENCY ANEMIA; JUVENILE CHRONIC ARTHRITIS; DERMATITIS-HERPETIFORMIS; INCREASED RISK; ADULT PATIENTS; NATIONWIDE COHORT; ALOPECIA-AREATA; FRACTURE RISK; RENAL-DISEASE AB Coeliac disease is a common disorder that can arise at any age and typically presents with a broad spectrum of symptoms. The disease is thought to be underdiagnosed, in part owing to the fact that coeliac disease is often characterized by associated conditions and extraintestinal manifestations that can misdirect and impede diagnosis. Some of these manifestations are direct consequences of autoimmunity, such as dermatitis herpetiformis or gluten ataxia, whereas others are indirectly related to inflammation and/or malabsorption including anaemia, osteoporosis, short stature and delayed puberty. Any organ from the central nervous system to joints, liver or teeth can be affected. In some cases, extraintestinal symptoms are the only clinical manifestations of coeliac disease or occur in conjunction with diarrhoea and malabsorptive symptoms. An increased awareness among medical practitioners of the variety of extraintestinal manifestations of coeliac disease is essential to improve diagnosis and treatment. C1 [Leffler, Daniel A.] Beth Israel Deaconess Med Ctr, Celiac Ctr, Boston, MA 02215 USA. [Green, Peter H. R.] Columbia Univ, Celiac Dis Ctr, New York, NY 10032 USA. [Fasano, Alessio] Massachusetts Gen Hosp, Ctr Celiac Res, Boston, MA 02114 USA. RP Fasano, A (reprint author), Massachusetts Gen Hosp, Ctr Celiac Res, 55 Fruit St, Boston, MA 02114 USA. EM afasano@mgh.harvard.edu FU Alba Therapeutics; Alvine Pharmaceuticals; Coronado Bioscience; Inova diagnostics; Ironwood Pharmaceuticals; Sidney Frank Foundation; Shire Pharmaceuticals; Immusan; Mead Johnson Nutrition; Pfizer Pharmaceutical FX D.A.L. has received funding from Alba Therapeutics, Alvine Pharmaceuticals, Coronado Bioscience, Inova diagnostics, Ironwood Pharmaceuticals, Sidney Frank Foundation and Shire Pharmaceuticals. P.H.R.G. has received funding from Alba Therapeutics, Alvine Pharmaceuticals and Immusan. A.F. has received funding from Alba Therapeutics, Inova diagnostics, Mead Johnson Nutrition and Pfizer Pharmaceutical. NR 144 TC 16 Z9 16 U1 4 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 EI 1759-5053 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD OCT PY 2015 VL 12 IS 10 BP 561 EP 571 DI 10.1038/nrgastro.2015.131 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT6LT UT WOS:000362925200007 PM 26260366 ER PT J AU Clemens, P Reay, D Bastacky, S Wack, K Stolz, D Robbins, R AF Clemens, P. Reay, D. Bastacky, S. Wack, K. Stolz, D. Robbins, R. TI D-amino acid substitution of peptide-mediated NF-kappa B suppression in mdx mice preserves therapeutic benefit in skeletal muscle, but causes kidney toxicity SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 20th International Congress of the World-Muscle-Society CY SEP 30-OCT 04, 2015 CL Brighton, ENGLAND SP World Muscle Soc C1 [Clemens, P.; Reay, D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Bastacky, S.; Wack, K.; Stolz, D.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Robbins, R.] Scripps Florida, Jupiter, FL USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2015 VL 25 SU 2 MA G.P.364 BP S294 EP S295 DI 10.1016/j.nmd.2015.06.388 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CT6LV UT WOS:000362925400384 ER PT J AU Uebelacker, LA Weisberg, RB Herman, DS Bailey, GL Pinkston-Camp, MM Stein, MD AF Uebelacker, Lisa A. Weisberg, Risa B. Herman, Debra S. Bailey, Genie L. Pinkston-Camp, Megan M. Stein, Michael D. TI Chronic Pain in HIV-Infected Patients: Relationship to Depression, Substance Use, and Mental Health and Pain Treatment SO PAIN MEDICINE LA English DT Article DE HIV; Chronic Pain; Depression ID CHRONIC BACK-PAIN; PRIMARY-CARE; ANTIRETROVIRAL THERAPY; IMMPACT RECOMMENDATIONS; MAJOR DEPRESSION; CLINICAL-TRIALS; SCREENING-TEST; USE DISORDERS; PREVALENCE; PRESCRIPTION AB ObjectiveAs the advent of highly active antiretroviral therapy, HIV has become a chronic disease for most individuals in developed countries. Chronic pain is a common occurrence for HIVinfected patients and has an impact on quality of life and antiretroviral adherence. The objective of this study was to examine relationships between chronic pain and depression, substance use, mental health treatment, and pain treatment in HIV-infected patients. DesignCross-sectional study. SettingThree primary care sites where HIV+ patients receive treatment. SubjectsTwo hundred and thirty eight HIV-infected primary care patients. MethodsWe collected self-report and chart-review information on demographics, HIV clinical status, chronic pain, depression, substance use, mental health treatment, and pain treatment. We collected data between October 2012 and November 2013. ResultsOf the patients enrolled in this study, 107 reported no chronic pain, 24 reported mild chronic pain, and 107 reported moderate-severe chronic pain. Participants in the moderate-severe pain group were more likely to have high levels of depressive symptoms than those in the no chronic pain group. Similarly, there was a significant relationship between chronic pain status and interference with life activities due to pain. Participants with moderate-severe chronic pain were more likely to be taking an antidepressant medication than those with mild chronic pain, and more likely to be taking a prescription opioid than the other two groups. We did not find a significant relationship between problematic substance use and chronic pain status. ConclusionsDespite pharmacologic treatment, moderate-severe chronic pain and elevated depression symptoms are common among HIV-infected patients and frequently co-occur. C1 [Uebelacker, Lisa A.; Herman, Debra S.; Stein, Michael D.] Butler Hosp, Providence, RI 02906 USA. [Uebelacker, Lisa A.; Weisberg, Risa B.; Herman, Debra S.; Bailey, Genie L.; Pinkston-Camp, Megan M.; Stein, Michael D.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Providence, RI 02912 USA. [Weisberg, Risa B.] Boston VA Healthcare Syst, Boston, MA USA. [Bailey, Genie L.] Stanley St Treatment & Resources, Fall River, MA USA. [Pinkston-Camp, Megan M.; Stein, Michael D.] Miriam Hosp, Ctr Immunol, Providence, RI 02906 USA. RP Uebelacker, LA (reprint author), Butler Hosp, 345 Blackstone Blvd, Providence, RI 02906 USA. EM luebelacker@butler.org FU National Institute of Nursing Research [NR013438]; Lifespan/Tufts/Brown Center for AIDS Research (CFAR) [2P30AI042853] FX This study was supported by grant NR013438 (MPIs: Uebelacker, Stein) from the National Institute of Nursing Research and the Lifespan/Tufts/Brown Center for AIDS Research (CFAR) grant 2P30AI042853 (PI: Carpenter). NR 50 TC 4 Z9 4 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD OCT PY 2015 VL 16 IS 10 BP 1870 EP 1881 DI 10.1111/pme.12799 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CT5YS UT WOS:000362887800004 PM 26119642 ER PT J AU Hawkins, EJ Malte, CA Grossbard, JR Saxon, AJ AF Hawkins, Eric J. Malte, Carol A. Grossbard, Joel R. Saxon, Andrew J. TI Prevalence and Trends of Concurrent Opioid Analgesic and Benzodiazepine Use Among Veterans Affairs Patients with Post-traumatic Stress Disorder, 2003-2011 SO PAIN MEDICINE LA English DT Article DE Chronic Pain; Trends in Benzodiazepine Use; Post-Traumatic Stress Disorder; Trends in Opioid Use; High-Risk Conditions ID PATIENTS PRESCRIBED OPIOIDS; CHRONIC PAIN PATIENTS; MENTAL-HEALTH; RISK-FACTORS; OVERDOSE DEATHS; PRESCRIPTION; THERAPY; ALCOHOL; DISCONTINUATION; METAANALYSIS AB BackgroundPatients with post-traumatic stress disorder (PTSD) have complex and multiple symptoms, including anxiety, insomnia, and co-occurring pain, often treated with opioids and benzodiazepines. While concurrent use of these medications poses safety concerns, little is known about the trends of long-term concurrent use and the prevalence of high-risk conditions among those who are prescribed them. Study objectives were to examine the trends in annual prevalence of long-term concurrent opioid and benzodiazepine use among patients with PTSD and prevalence of high-risk conditions in concurrent users of these medications. DesignRetrospective review of pharmacy records of the Veteran Affairs Northwest Integrated Network (VISN20). SubjectsPatients (n=66,210) with PTSD receiving care during 2003-2011. MethodsConcurrent use was defined as overlapping opioid and benzodiazepine prescriptions for 90 consecutive days. Gender-specific logistic regressions estimated long-term concurrent use of these medications and tested for linear trends over 9-years. ResultsThe trend in age-adjusted long-term concurrent opioid and benzodiazepine use over 9-years increased 52.7%, from 3.6% (95% confidence interval, 3.3-3.9%) to 5.5% (5.3-5.8%), in men and 79.5%, from 3.9% (3.0-5.0%) to 7.0% (6.2-7.9%), in women. In 2011, 17.1% of long-term concurrent users were prescribed morphine-equivalent daily doses of opioids 100 mg and 49.4% had a documented high-risk condition. ConclusionDespite known risks associated with prescribing opioids and benzodiazepines concurrently, the adjusted prevalence of long-term concurrent use rose significantly among men and women with PTSD in VISN20 over a 9-year period. Common use of these medications among patients with high-risk conditions suggests comprehensive strategies are needed to identify and monitor patients at increased risk for adverse outcomes. C1 [Hawkins, Eric J.; Malte, Carol A.; Saxon, Andrew J.] Hlth Serv Res & Dev HSR&D Seattle Ctr Innovat Vet, Seattle, WA USA. [Hawkins, Eric J.; Malte, Carol A.; Grossbard, Joel R.; Saxon, Andrew J.] Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Hawkins, Eric J.; Malte, Carol A.; Saxon, Andrew J.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Hawkins, Eric J.; Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Hawkins, EJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div S116ATC, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Eric.Hawkins@va.gov NR 61 TC 4 Z9 4 U1 5 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD OCT PY 2015 VL 16 IS 10 BP 1943 EP 1954 DI 10.1111/pme.12787 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CT5YS UT WOS:000362887800011 PM 26332513 ER PT J AU Harden, P Ahmed, S Ang, K Wiedemer, N AF Harden, Paul Ahmed, Sara Ang, Katie Wiedemer, Nancy TI Clinical Implications of Tapering Chronic Opioids in a Veteran Population SO PAIN MEDICINE LA English DT Article DE Tapering; Opioids; Veteran; Chronic ID CHRONIC NONCANCER PAIN; LOW-BACK-PAIN; TRANSDERMAL FENTANYL; THERAPY; OVERDOSE; HEALTH; METAANALYSIS; ASSOCIATION; DEATHS; SAFETY AB ObjectiveTo determine if patients receiving chronic opioid therapy can be tapered to lower opioid doses without a subsequent increase in pain. DesignRetrospective and prospective chart review at a VA Medical Center. MethodsPatients were included in the review if they were prescribed opioids chronically for at least 90 consecutive days and if a plan to taper opioid doses was agreed upon. Patients 89 years of age and older, patients with cancer, and patients exhibiting aberrant behavior were excluded. The primary endpoint was to determine the percent reduction of morphine equivalents (ME) over a 12-month period. Secondary endpoints included percent reduction of ME at 3 and 6 months, change in pain perception at 3, 6, and 12 months, and change in the number of adjuvant medications prescribed at 3, 6, and 12 months. Data were analyzed utilizing descriptive statistics. ResultsA total of 50 patient charts were included in the study. The average percent reduction of opioid doses was 46% over a 12-month period. Seventy percent of patients either experienced no change in pain or had less pain when comparing baseline to 12 months. An equal percentage of patients either had no change in the number of adjuvant medications prescribed or had more adjuvant medications prescribed when comparing baseline to 12 months. ConclusionsPatients in the population studied can be successfully tapered to lower opioid doses and may not necessarily experience more pain. C1 [Harden, Paul; Ahmed, Sara; Ang, Katie; Wiedemer, Nancy] Philadelphia VA Med Ctr, Dept Pharm, Philadelphia, PA USA. RP Harden, P (reprint author), 3900 Woodland Ave,Pharm Serv 119, Philadelphia, PA 19104 USA. EM paul.harden@va.gov NR 24 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD OCT PY 2015 VL 16 IS 10 BP 1975 EP 1981 DI 10.1111/pme.12812 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CT5YS UT WOS:000362887800014 PM 26119793 ER PT J AU Chen, HL Ding, D Wang, J Zhao, QH Meng, HJ Li, HL Gao, YT Shu, XO Tanner, CM Hong, Z Yang, G AF Chen, Honglei Ding, Ding Wang, Jian Zhao, Qianhua Meng, Haijiao Li, Honglan Gao, Yu-Tang Shu, Xiao-Ou Tanner, Caroline M. Hong, Zhen Yang, Gong TI Parkinson's disease research in a prospective cohort in China SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease/Parkinsonism; Risk factors in epidemiology; Cohort studies ID ORGANOCHLORINE PESTICIDES; DIETARY PATTERNS; RISK; PREVALENCE; SMOKING; HEALTH; SERUM; EPIDEMIOLOGY; ASSOCIATION; POPULATION AB Introduction: China has the largest population of Parkinson's disease (PD) patients; however few etiological studies of PD have been conducted in China. Methods: The Shanghai Women's Health Study recruited 74,941 women in urban Shanghai, aged 40 to 70, from 1996 to 2000. Self-reported PD cases were invited for a neurological examination and diagnoses were made by a movement disorder specialist. Results: This cohort had very few smokers (2.7%), alcohol drinkers (2.3%), and post-menopausal hormone users (4.3%); however, tea drinking (29.9%) and exposure to tobacco smoke from husbands (61.8%) were common. A total of 301 participants reported PD diagnosis during the follow-up. The diagnosis was confirmed in 76 (57%) of the 133 clinically examined patients. An additional 19 (53%) PD cases were identified out of 36 participants who self-confirmed the diagnosis and provided a history on PD symptoms and treatments. As expected, increasing age was strongly associated with PD risk. Further, PD risk appears to be inversely associated with exposures to second-hand tobacco smoke from husbands and tea drinking, and positively with education, although none of these reached statistical significance. The age-adjusted odds ratio (OR) was 0.7 (95% confidence interval; 0.4-1.1) for participants whose husbands were current smokers at baseline and 0.8 (0.5-1.3) for ever tea-drinkers. Compared with primary education or lower, the age-adjusted OR was 1.3 (0.7-2.4) for middle school and 1.6 (1.0-2.7) for high school or above. Conclusion: PD research in this unique cohort is feasible and, with extended follow-up, will allow for prospective PD etiological research in China. Published by Elsevier Ltd. C1 [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Ding, Ding; Wang, Jian; Zhao, Qianhua; Meng, Haijiao; Hong, Zhen] Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai 200433, Peoples R China. [Shu, Xiao-Ou; Yang, Gong] Vanderbilt Univ, Nashville, TN 37235 USA. [Li, Honglan; Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Tanner, Caroline M.] Univ Calif San Francisco, Dis Res Educ & Clin Ctr, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Tanner, Caroline M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov OI Chen, Honglei/0000-0003-3446-7779 FU Intramural Research Program of NIH; National Institute of Environmental Health Sciences [Z01-ES-101986]; NIH [R37CA070867, UM1CA182910] FX The study was supported by the Intramural Research Program of NIH, the National Institute of Environmental Health Sciences (Z01-ES-101986) and in part by NIH Grant R37CA070867 and UM1CA182910. NR 30 TC 3 Z9 3 U1 3 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD OCT PY 2015 VL 21 IS 10 BP 1200 EP 1204 DI 10.1016/j.parkreldis.2015.08.020 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA CT5OB UT WOS:000362858600011 PM 26318964 ER PT J AU Siu, AL Bibbins-Domingo, K Grossman, D Baumann, LC Davidson, KW Ebell, M Garcia, FAR Gillman, M Herzstein, J Kemper, AR Krist, AH Kurth, AE Owens, DK Phillips, WR Phipps, MG Pignone, MP Moyer, V Flores, G AF Siu, Albert L. Bibbins-Domingo, Kirsten Grossman, David Baumann, Linda Ciofu Davidson, Karina W. Ebell, Mark Garcia, Francisco A. R. Gillman, Matthew Herzstein, Jessica Kemper, Alex R. Krist, Alexander H. Kurth, Ann E. Owens, Douglas K. Phillips, William R. Phipps, Maureen G. Pignone, Michael P. Moyer, Virginia Flores, Glen CA US Preventive Serv Task Force TI Screening for Iron Deficiency Anemia in Young Children: USPSTF Recommendation Statement SO PEDIATRICS LA English DT Article ID INFANTS; AGE AB DESCRIPTION: Update of the US Preventive Services Task Force (USPSTF) 2006 recommendation on screening for iron deficiency anemia. METHODS: The USPSTF reviewed the evidence on the association between change in iron status as a result of intervention and improvement in child health outcomes, as well as screening for and treatment of iron deficiency anemia with oral iron formulations, in children ages 6 to 24 months. POPULATION: This recommendation applies to children ages 6 to 24 months living in the United States who are asymptomatic for iron deficiency anemia. It does not apply to children younger than age 6 months or older than 24 months, children who are severely malnourished, children who were born prematurely or with low birth weight, or children who have symptoms of iron deficiency anemia. RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for iron deficiency anemia in children ages 6 to 24 months. (I statement) C1 [Siu, Albert L.] Mt Sinai Sch Med, New York, NY USA. [Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Grossman, David] Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. [Baumann, Linda Ciofu] Univ Wisconsin, Madison, WI USA. [Davidson, Karina W.] Columbia Univ, New York, NY USA. [Ebell, Mark] Univ Georgia, Athens, GA 30602 USA. [Garcia, Francisco A. R.] Pima Cty Dept Hlth, Tucson, AZ USA. [Gillman, Matthew] Harvard Univ, Sch Med, Boston, MA USA. [Gillman, Matthew] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Kemper, Alex R.] Duke Univ, Durham, NC USA. [Krist, Alexander H.] Fairfax Family Practice, Fairfax, VA USA. [Krist, Alexander H.] Virginia Commonwealth Univ, Richmond, VA USA. [Kurth, Ann E.] NYU, New York, NY USA. [Owens, Douglas K.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Owens, Douglas K.] Stanford Univ, Stanford, CA 94305 USA. [Phillips, William R.] Univ Washington, Seattle, WA 98195 USA. [Phipps, Maureen G.] Brown Univ, Providence, RI 02912 USA. [Pignone, Michael P.] Univ N Carolina, Chapel Hill, NC USA. RP Siu, AL (reprint author), 540 Gaither Rd, Rockville, MD 20850 USA. EM coordinator@uspstf.net NR 18 TC 5 Z9 5 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD OCT PY 2015 VL 136 IS 4 BP 746 EP 752 DI 10.1542/peds.2015-2567 PG 7 WC Pediatrics SC Pediatrics GA CT6TC UT WOS:000362944300061 PM 26347426 ER PT J AU Tabri, N Murray, HB Thomas, JJ Franko, DL Herzog, DB Eddy, KT AF Tabri, N. Murray, H. B. Thomas, J. J. Franko, D. L. Herzog, D. B. Eddy, K. T. TI Overvaluation of body shape/weight and engagement in non-compensatory weight-control behaviors in eating disorders: is there a reciprocal relationship? SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Anorexia nervosa; body image; bulimia nervosa; cognitive-behavioral therapy; eating disorders ID ATYPICAL ANOREXIA-NERVOSA; FOLLOW-UP EVALUATION; BULIMIA-NERVOSA; DIETARY RESTRAINT; ADOLESCENT GIRLS; SHAPE; THERAPY; PREDICTORS; SYMPTOMS; RELAPSE AB Background. Overvaluation of body shape/weight is thought to be the core psychopathology underlying eating disorders, which propels engagement in non-compensatory weight-control behaviors. In turn, these behaviors lead to binge eating and/or maintenance of low weight thereby reinforcing overvaluation. The present study investigated the reciprocal relationship between overvaluation and engagement in non-compensatory weight-control behaviors (defined in two ways: restrictive eating and compulsive exercise) among women diagnosed with anorexia nervosa or bulimia nervosa (N = 237). Method. Participants completed clinical interviews in which weekly eating disorder symptoms and behaviors were assessed over 2 years. Results. Overvaluation on a given week was associated with greater engagement in non-compensatory weight-control behaviors during the following week. Further, engagement in non-compensatory weight-control behaviors on a given week was associated with greater overvaluation during the following week. These findings held true regardless of participants' shape/weight concerns (feelings of fatness and fat phobia), and eating disorder diagnosis. Conclusions. Our data provide empirical support for key aspects of the transdiagnostic cognitive-behavioral model of eating disorders and suggest that targeting non-compensatory weight-control behaviors in treatment may help alleviate overvaluation and shape/weight concerns. C1 [Tabri, N.; Murray, H. B.; Thomas, J. J.; Franko, D. L.; Eddy, K. T.] Massachusetts Gen Hosp, Dept Psychiat, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Tabri, N.; Thomas, J. J.; Herzog, D. B.; Eddy, K. T.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Franko, D. L.] Northeastern Univ, Boston, MA USA. RP Eddy, KT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Eating Disorders Clin & Res Program, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. EM keddy@mgh.harvard.edu FU NIMH [MH-38333] FX The research was supported by an NIMH grant MH-38333 (PI D.B.H). NR 40 TC 4 Z9 4 U1 7 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2015 VL 45 IS 14 BP 2951 EP 2958 DI 10.1017/S0033291715000896 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CT7EQ UT WOS:000362977100004 PM 25994276 ER PT J AU Shomaker, LB Goodman, E AF Shomaker, Lauren B. Goodman, Elizabeth TI An 8-Year Prospective Study of Depressive Symptoms and Change in Insulin From Adolescence to Young Adulthood SO PSYCHOSOMATIC MEDICINE LA English DT Article DE depression; insulin; race; ethnicity; adolescents; young adults; BMI = body mass index; CES-D = Center for Epidemiological Studies-Depression Scale; PSD = Princeton School District ID TYPE-2 DIABETES-MELLITUS; CHILDHOOD PREDICTORS; SOCIOECONOMIC-STATUS; CO-MORBIDITY; RISK-FACTOR; RESISTANCE; METAANALYSIS; PREVALENCE; CHILDREN; OBESITY AB Objective To evaluate whether depressive symptoms predict change in fasting insulin among adolescents followed into young adulthood. We hypothesized that higher depressive symptoms would predict increased insulin and that puberty and race/ethnicity would moderate this relationship. Methods Data came from the Princeton School District Study, a school-based longitudinal cohort of non-Hispanic black and white adolescents (2001-2011). Depressive symptoms, fasting insulin, and body mass index were measured at baseline (adolescence) and 8 years later (young adulthood) in 685 participants. Puberty was assessed using a validated protocol measuring sex steroids and physical changes. The primary outcome was change in fasting insulin. Analyses accounted for age, sex, race, parental education, baseline insulin, body mass index z score, puberty, and time to follow-up. Results At baseline, depressive symptoms were correlated with insulin ( = 0.13, p = .001). High baseline insulin predicted insulin change (B = -11.50, standard error [SE] = 2.30, p < .001). Depressive symptoms also predicted insulin change, but only for pubertal adolescents (B = -0.23, SE = 0.11, p = .038). This relationship was moderated by race (p = .047); depressive symptoms predicted insulin change only among pubertal black adolescents (p = .030), not white (p = .49), and in the direction opposite that hypothesized (B-blacks = -0.51, SE = 0.23). Post hoc analyses revealed that pubertal black adolescents with high depressive symptoms had the highest baseline insulin, which stayed high across the follow-up period. Conclusions Among pubertal black adolescents, elevated depressive symptoms are associated with increased risk for sustained hyperinsulinemia from adolescence into adulthood. These youths may be particularly vulnerable for Type 2 diabetes. C1 [Shomaker, Lauren B.] Colorado State Univ, Dept Human Dev & Family Studies, Colorado Sch Publ Hlth, Ft Collins, CO 80523 USA. [Shomaker, Lauren B.] Colorado State Univ, Colorado Sch Publ Hlth, Coll Hlth & Human Sci, Ft Collins, CO 80523 USA. [Goodman, Elizabeth] Harvard Univ, Sch Med, Div Gen Acad Pediat, MassGen Hosp Children, Boston, MA USA. [Goodman, Elizabeth] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Goodman, E (reprint author), MassGen Hosp Children, Div Gen Acad Pediat, 100 Cambridge St,Room 1570, Boston, MA 02114 USA. EM egoodman3@mgh.harvard.edu FU National Institutes of Health [HD041527, DK59183, HD069516] FX This work was funded, in part, by the National Institutes of Health grants HD041527 (E.G.), DK59183, and HD069516 (L.B.S.). Neither author has a conflict of interest to report. NR 62 TC 0 Z9 0 U1 3 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD OCT PY 2015 VL 77 IS 8 BP 938 EP 945 DI 10.1097/PSY.0000000000000230 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA CT3LH UT WOS:000362707700011 PM 26368574 ER PT J AU Della-Torre, E Campochiaro, C Bozzolo, EP Dagna, L Scotti, R Nicoletti, R Stone, JH Sabbadini, MG AF Della-Torre, Emanuel Campochiaro, Corrado Bozzolo, Enrica Paola Dagna, Lorenzo Scotti, Raffaella Nicoletti, Roberto Stone, John H. Sabbadini, Maria Grazia TI Methotrexate for maintenance of remission in IgG4-related disease SO RHEUMATOLOGY LA English DT Letter C1 [Della-Torre, Emanuel; Campochiaro, Corrado; Dagna, Lorenzo; Sabbadini, Maria Grazia] Univ Vita Salute San Raffaele, Milan, Italy. [Della-Torre, Emanuel; Campochiaro, Corrado; Bozzolo, Enrica Paola; Dagna, Lorenzo; Scotti, Raffaella; Sabbadini, Maria Grazia] IRCCS San Raffaele Sci Inst, Unit Med & Clin immunol, I-20132 Milan, Italy. [Nicoletti, Roberto] IRCCS San Raffaele Sci Inst, Dept Radiol, I-20132 Milan, Italy. [Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Della-Torre, E (reprint author), IRCCS San Raffaele Sci Inst, Unit Med & Clin Immunol, Via Olgettina 60, I-20132 Milan, Italy. EM dellatorre.emanuel@hsr.it OI Della Torre, Emanuel/0000-0002-9192-4270 NR 8 TC 5 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD OCT PY 2015 VL 54 IS 10 BP 1934 EP 1936 DI 10.1093/rheumatology/kev244 PG 4 WC Rheumatology SC Rheumatology GA CT5KS UT WOS:000362849200026 PM 26139657 ER PT J AU Peltan, ID Shiga, T Gordon, JA Currier, PF AF Peltan, Ithan D. Shiga, Takashi Gordon, James A. Currier, Paul F. TI Simulation Improves Procedural Protocol Adherence During Central Venous Catheter Placement A Randomized Controlled Trial SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Article DE Central venous catheter; Simulation; Graduate medical education; Procedure training ID INTENSIVE-CARE-UNIT; CENTRAL VEIN CATHETERIZATION; BLOOD-STREAM INFECTIONS; DELIBERATE PRACTICE; MEDICINE RESIDENTS; TRAINING-PROGRAM; TECHNICAL SKILLS; PERFORMANCE; EDUCATION; INSERTION AB Background Simulation training may improve proficiency at and reduce complications from central venous catheter (CVC) placement, but the scope of simulation's effect remains unclear. This randomized controlled trial evaluated the effects of a pragmatic CVC simulation program on procedural protocol adherence, technical skill, and patient outcomes. Methods Internal medicine interns were randomized to standard training for CVC insertion or standard training plus simulation-based mastery training. Standard training involved a lecture, a video-based online module, and instruction by the supervising physician during actual CVC insertions. Intervention-group subjects additionally underwent supervised training on a venous access simulator until they demonstrated procedural competence. Raters evaluated interns' performance during internal jugular CVC placement on actual patients in the medical intensive care unit. Generalized estimating equations were used to account for outcome clustering within trainees. Results We observed 52 interns placing 87 CVCs. Simulation-trained interns exhibited better adherence to prescribed procedural technique than interns who received only standard training (P = 0.024). There were no significant differences detected in first-attempt or overall cannulation success rates, mean needle passes, global assessment scores, or complication rates. Conclusions Simulation training added to standard training improved protocol adherence during CVC insertion by novice practitioners. This study may have been too small to detect meaningful differences in venous cannulation proficiency and other clinical outcomes, highlighting the difficulty of patient-centered simulation research in settings where poor outcomes are rare. For high-performing systems, where protocol deviations may provide an important proxy for rare procedural complications, simulation may improve CVC insertion quality and safety. C1 [Peltan, Ithan D.; Currier, Paul F.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Peltan, Ithan D.] Univ Washington, Med Ctr, Div Pulm & Crit Care Med, Seattle, WA USA. [Shiga, Takashi; Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Boston, MA 02114 USA. [Shiga, Takashi] Tokyo Bay Urayasu Ichikawa Med Ctr, Dept Emergency Med, Chiba, Japan. [Gordon, James A.] Massachusetts Gen Hosp, MGH Learning Lab, Boston, MA 02114 USA. [Currier, Paul F.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. RP Peltan, ID (reprint author), Univ Washington, Med Ctr, 1959 NE Pacific St,Campus Box 356522, Seattle, WA 98195 USA. EM ipeltan@post.harvard.edu FU Lucian Leape Foundation for Patient Safety; National Institutes of Health [UL1 TR001102] FX Reprints: Ithan D. Peltan, MD, University of Washington Medical Center, 1959 NE Pacific St., Campus Box 356522, Seattle, WA, 98195, (e-mail: ipeltan@post.harvard.edu). Supported by a grant from the Lucian Leape Foundation for Patient Safety and funding from the National Institutes of Health (UL1 TR001102) for the Harvard Catalyst Clinical and Translational Science Center. NR 45 TC 2 Z9 2 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-2332 EI 1559-713X J9 SIMUL HEALTHC JI Simul. Healthc. PD OCT PY 2015 VL 10 IS 5 BP 270 EP 276 DI 10.1097/SIH.0000000000000096 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CT3PW UT WOS:000362720100003 PM 26154250 ER PT J AU McCullough, J Goldfinger, D Gorlin, J Riley, WJ Sandhu, H Stowell, C Ward, D Clay, M Pulkrabek, S Chrebtow, V Stassinopoulos, A AF McCullough, Jeffrey Goldfinger, Dennis Gorlin, Jed Riley, William J. Sandhu, Harpreet Stowell, Christopher Ward, Dawn Clay, Mary Pulkrabek, Shelley Chrebtow, Vera Stassinopoulos, Adonis TI Cost implications of implementation of pathogen-inactivated platelets SO TRANSFUSION LA English DT Article ID VERSUS-HOST-DISEASE; UNITED-STATES; APHERESIS PLATELETS; BLOOD-DONORS; PHOTOCHEMICAL TREATMENT; BABESIA-MICROTI; HEALTH-CARE; COMPONENTS; INFECTIONS; IMPACT AB BACKGROUNDPathogen inactivation (PI) is a new approach to blood safety that may introduce additional costs. This study identifies costs that could be eliminated, thereby mitigating the financial impact. STUDY DESIGN AND METHODSCost information was obtained from five institutions on tests and procedures (e.g., irradiation) currently performed, that could be eliminated. The impact of increased platelet (PLT) availability due to fewer testing losses, earlier entry into inventory, and fewer outdates with a 7-day shelf life were also estimated. Additional estimates include costs associated with managing 1) special requests and 2) test results, 3) quality control and proficiency testing, 4) equipment acquisition and maintenance, 5) replacement of units lost to positive tests, 6) seasonal or geographic testing, and 7) health department interactions. RESULTSAll costs are mean values per apheresis PLT unit in USD ($/unit). The estimated test costs that could be eliminated are $71.76/unit and a decrease in transfusion reactions corresponds to $2.70/unit. Avoiding new tests (e.g., Babesia and dengue) amounts to $41.80/unit. Elimination of irradiation saves $8.50/unit, while decreased outdating with 7-day storage can be amortized to $16.89/unit. Total potential costs saved with PI is $141.65/unit. Costs are influenced by a variety of factors specific to institutions such as testing practices and the location in which such costs are incurred and careful analysis should be performed. Additional benefits, not quantified, include retention of some currently deferred donors and scheduling flexibility due to 7-day storage. CONCLUSIONSWhile PI implementation will result in additional costs, there are also potential offsetting cost reductions, especially after 7-day storage licensing. C1 [McCullough, Jeffrey; Clay, Mary; Pulkrabek, Shelley] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Goldfinger, Dennis; Ward, Dawn] Univ Calif Los Angeles, David Geffen Sch Med, Dept Lab Med & Pathol, Los Angeles, CA 90095 USA. [Gorlin, Jed] Mem Blood Ctr, Innovat Blood Resources, St Paul, MN USA. [Riley, William J.] Arizona State Univ, Coll Sci Hlth Care Delivery, Tempe, AZ USA. [Sandhu, Harpreet] Stanford Univ, Sch Med, Stanford Blood Ctr, Stanford, CA 94305 USA. [Stowell, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chrebtow, Vera; Stassinopoulos, Adonis] Cerus Corp, Global Sci Affairs, Concord, CA USA. RP McCullough, J (reprint author), Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. EM mccul001@umn.edu FU Cerus Corp. FX This study was funded in part by Cerus Corp. NR 47 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD OCT PY 2015 VL 55 IS 10 BP 2312 EP 2320 DI 10.1111/trf.13149 PG 9 WC Hematology SC Hematology GA CT6HQ UT WOS:000362914500005 PM 25989465 ER PT J AU Marshall, AL Goodarzi, K Kuter, DJ AF Marshall, Ariela L. Goodarzi, Katayoon Kuter, David J. TI Romiplostim in the management of the thrombocytopenic surgical patient SO TRANSFUSION LA English DT Article ID LONG-TERM TREATMENT; PLATELET PRODUCTION; MYELODYSPLASTIC SYNDROME; IMMUNE THROMBOCYTOPENIA; HEPATITIS-C; CHRONIC ITP; THROMBOPOIETIN; EFFICACY; ELTROMBOPAG; CIRRHOSIS AB BACKGROUNDThrombopoietin receptor agonists increase platelet (PLT) counts and are approved for the treatment of chronic immune thrombocytopenia (ITP). These agents may also be useful for the management of thrombocytopenia in patients requiring surgical procedures. STUDY DESIGN AND METHODSWe conducted a retrospective review of patients with thrombocytopenia (baseline PLT count, <150 x 10(9)/L) who received romiplostim before planned operative procedures. We characterized patient demographics, dosing and duration of romiplostim use, success in achieving PLT counts high enough for surgery, and clinical outcomes. RESULTSEighteen patients underwent a total of 22 operative procedures, including three Jehovah's Witnesses who underwent five procedures. Etiologies of thrombocytopenia included mild ITP (not on romiplostim at baseline), liver disease, hematologic malignancy, and drug-related thrombocytopenia. Median PLT count at romiplostim initiation was 47 x 10(9)/L (range, 11 x 10(9)-120 x 10(9)/L). All patients experienced a PLT count increase over a median of 4 weeks; median PLT count at surgery was 144 x 10(9)/L (range, 28 x 10(9)-370 x 10(9)/L). PLT counts increase to more than 150 x 10(9)/L in four of five Jehovah's Witness patients by the time of surgery. There were no surgical delays or cancellations due to thrombocytopenia. Four bleeding events occurred; none were fatal and none occurred at a PLT count of fewer than 80 x 10(9)/L. No definitive thromboembolic events occurred. CONCLUSIONRomiplostim successfully increased preoperative PLT counts allowing operative interventions, was well tolerated, did not lead to any significant thromboembolic events, and avoided the need for transfusion. Romiplostim may be of clinical utility in the preoperative management of thrombocytopenic patients, especially those unable to receive or unresponsive to PLT transfusion. C1 [Marshall, Ariela L.; Goodarzi, Katayoon; Kuter, David J.] Massachusetts Gen Hosp, Dept Hematol, Boston, MA 02114 USA. [Marshall, Ariela L.] Dana Farber Canc Inst, Dept Hematol & Med Oncol, Boston, MA 02115 USA. RP Marshall, AL (reprint author), 55 Fruit St,Profess Off Bldg Room 221, Boston, MA 02114 USA. EM ariela_marshall@dfci.harvard.edu NR 22 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD OCT PY 2015 VL 55 IS 10 BP 2505 EP 2510 DI 10.1111/trf.13181 PG 6 WC Hematology SC Hematology GA CT6HQ UT WOS:000362914500028 PM 26033367 ER PT J AU McGreevy, J Isaacs, E Marill, K Venkat, A AF McGreevy, Jolion Isaacs, Eric Marill, Keith Venkat, Arvind CA Soc Acad Emergency Med Ethics Comm TI Ethical Decision-making in the Emergency Department SO ACADEMIC EMERGENCY MEDICINE LA English DT Editorial Material C1 [McGreevy, Jolion] Boston Med Ctr, Dept Emergency Med, Boston, MA 02118 USA. [McGreevy, Jolion] Boston Univ, Sch Med, Boston, MA 02118 USA. [Isaacs, Eric] Univ Calif San Francisco, Sch Med, Dept Emergency Med, San Francisco, CA USA. [Marill, Keith] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Marill, Keith] Univ Pittsburgh, Sch Med, Dept Emergency Med, Pittsburgh, PA USA. [Venkat, Arvind] Allegheny Hlth Network, Dept Emergency Med, Pittsburgh, PA USA. RP McGreevy, J (reprint author), Boston Med Ctr, Dept Emergency Med, Boston, MA 02118 USA. EM avenkat@wpahs.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2015 VL 22 IS 10 BP 1196 EP 1196 DI 10.1111/acem.12758 PG 1 WC Emergency Medicine SC Emergency Medicine GA CT1YY UT WOS:000362600400010 PM 26390121 ER PT J AU Caterino, JM Hains, DS Camargo, CA Quraishi, SA Saxena, V Schwaderer, AL AF Caterino, Jeffrey M. Hains, David S. Camargo, Carlos A. Quraishi, Sadeq A. Saxena, Vijay Schwaderer, Andrew L. TI A Prospective, Observational Pilot Study of the Use of Urinary Antimicrobial Peptides in Diagnosing Emergency Department Patients With Positive Urine Cultures SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID TRACT-INFECTION AB Objectives: Urinary tract infection (UTI) often represents a diagnostic challenge in the emergency department (ED) where urine culture results are generally not available and other tests demonstrate limited sensitivity and specificity. Antimicrobial peptides (AMPs) are components of the innate immune system that have demonstrated increased urinary levels in response to infection both in children and in adults with chronic UTI. The objective of this study was to determine the relationship between urinary AMP levels and positive urine cultures in adult ED patients with suspected UTI. Methods: This was a prospective, observational study of adult ED patients with suspected UTI. Enzyme-linked immunosorbent assays were performed to measure urine levels of AMPs: human neutrophil peptides 1-3 (HNP1-3), human -defensin 5 (HD5), human beta defensin 2 (hBD-2), and cathelicidin (LL-37). Comparisons between positive and negative cultures were performed using Wilcoxon rank sum tests and receiver operating characteristic curves, with calculation of area under the curve (AUC). Data were also analyzed for the older adult subgroup. Results: Of 40 patients enrolled, 23 (58%) were 65 years, 25 were female (64%), and seven (17%) were nonwhite. Cultures were positive in 13 (32%), including seven in those 65 years old. HNP1-3, HD5, and hBD-2 levels were significantly higher in those with positive than negative urine cultures. Median HNP1-3 was 5.39 ng/mg (interquartile range [IQR] = 2.74 to 11.09) in positive vs. 0.81 ng/mg (IQR = 0.06 to 3.87) in negative cultures. Median HD5 was 4.75 pg/mg (IQR = 1.6 to 22.7) in positive versus 0.00 pg/mg (IQR = 0 to 2.60) in negative cultures, and median hBD-2 was 0.13 pg/mg (IQR = 0.08 to 0.17) in positive versus 0.02 pg/mg (IQR = 0 to 0.04) in negative cultures (p < 0.05 for all). Findings were similar for adults 65 years. The AUC was 0.75 for all three AMPs, both overall and in the older adult subgroup. LL-37 was not significantly higher in patients with positive urine culture. However, LL-37 expression is vitamin D dependent, and inadequate serum levels (< 30 ng/mL) were present in 72% of those tested. Conclusions: Urinary levels of HNP1-3, HD5, and hBD-2 are significantly greater in the presence of positive urine cultures in ED patients with suspected UTI. These findings are maintained in the high-risk subgroup of older adults. (C) 2015 by the Society for Academic Emergency Medicine C1 [Caterino, Jeffrey M.] Ohio State Univ, Dept Emergency Med, Wexner Med Ctr, Columbus, OH 43210 USA. [Hains, David S.] Univ Tennessee, Hlth Sci Ctr, Dept Pediat, Div Nephrol, Memphis, TN USA. [Camargo, Carlos A.] Massachusetts Gen, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A.] Massachusetts Gen, Dept Epidemiol, Boston, MA USA. [Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Saxena, Vijay; Schwaderer, Andrew L.] Nationwide Childrens Hosp, Div Nephrol, Dept Pediat, Columbus, OH USA. RP Caterino, JM (reprint author), Ohio State Univ, Dept Emergency Med, Wexner Med Ctr, Columbus, OH 43210 USA. EM jeffrey.caterino@osumc.edu RI Schwaderer, Andrew/E-4049-2011; OI Hains, David/0000-0001-6511-9561 FU National Institute on Aging [1K23AG03835101] FX Dr. Caterino's work on this study was supported in part by 1K23AG03835101 from the National Institute on Aging. NR 10 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2015 VL 22 IS 10 BP 1226 EP 1230 DI 10.1111/acem.12770 PG 5 WC Emergency Medicine SC Emergency Medicine GA CT1YY UT WOS:000362600400016 PM 26375724 ER PT J AU Freudenreich, O AF Freudenreich, O. TI Clozapine-induced myocarditis: prescribe safely but do prescribe SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Erich Lindemann Mental Hlth Ctr, Boston, MA 02114 USA. RP Freudenreich, O (reprint author), Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Erich Lindemann Mental Hlth Ctr, Boston, MA 02114 USA. EM Freudenreich.Oliver@mgh.harvard.edu NR 15 TC 4 Z9 4 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD OCT PY 2015 VL 132 IS 4 BP 240 EP 241 DI 10.1111/acps.12425 PG 3 WC Psychiatry SC Psychiatry GA CT0UQ UT WOS:000362513200003 PM 25865876 ER PT J AU Yen, S Frazier, E Hower, H Weinstock, LM Topor, DR Hunt, J Goldstein, TR Goldstein, BI Gill, MK Ryan, ND Strober, M Birmaher, B Keller, MB AF Yen, S. Frazier, E. Hower, H. Weinstock, L. M. Topor, D. R. Hunt, J. Goldstein, T. R. Goldstein, B. I. Gill, M. K. Ryan, N. D. Strober, M. Birmaher, B. Keller, M. B. TI Borderline personality disorder in transition age youth with bipolar disorder SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE bipolar disorder; borderline personality disorder; comorbidity; longitudinal ID DIALECTICAL BEHAVIOR-THERAPY; NONSUICIDAL SELF-INJURY; CONFIRMATORY FACTOR-ANALYSIS; SPECTRUM DISORDERS; II DISORDER; AFFECTIVE INSTABILITY; FOLLOW-UP; ADOLESCENTS; COMORBIDITY; DIAGNOSIS AB Objective: To determine the longitudinal impact of borderline personality disorder (BPD) on the course and outcome of bipolar disorder (BP) in a pediatric BP sample. Method: Participants (N = 271) and parents from the Course and Outcome of Bipolar Youth (COBY) study were administered structured clinical interviews and self-reports on average every 8.7 months over a mean of 93 months starting at age 13.0 +/- 3.1 years. The structured interview for DSM-IV personality disorders (SIDP-IV) was administered at the first follow-up after age 18 to assess for symptoms of BPD. BPD operationalized at the disorder, factor, and symptom level, was examined as a predictor of poor clinical course of BP using all years of follow-up data. Results: The number of BPD symptoms was significantly associated with poor clinical course of BP, above and beyond BP characteristics. Affective dysregulation was most strongly associated with poor course at the factor level; the individual symptoms most strongly associated with poor course were dissociation/stress-related paranoid ideation, impulsivity, and affective instability. Conclusion: BPD severity adds significantly to the burden of BP illness and is significantly associated with a more chronic and severe course and outcome beyond what can be attributable to BP characteristics. C1 [Yen, S.; Frazier, E.; Hower, H.; Weinstock, L. M.; Hunt, J.] Brown Univ, Alpert Med Ctr, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Yen, S.; Weinstock, L. M.; Keller, M. B.] Butler Hosp, Providence, RI USA. [Frazier, E.; Hunt, J.] Emma Pendleton Bradley Hosp, East Providence, RI USA. [Topor, D. R.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. [Goldstein, T. R.; Gill, M. K.; Ryan, N. D.; Birmaher, B.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. [Goldstein, B. I.] Univ Toronto, Med Ctr, Sunnybrook Hlth Sci Ctr, Dept Child Psychiat, Toronto, ON, Canada. [Strober, M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Yen, S (reprint author), Brown Univ, Alpert Med Ctr, Butler Hosp, Dept Psychiat & Human Behav, 700 Butler Dr, Providence, RI 02906 USA. EM Shirley_Yen_Phd@Brown.edu OI Weinstock, Lauren/0000-0001-9970-235X FU NIMH [MH59691, MH059929, MH59977]; Pfizer; Resnick Endowed Chair in Eating Disorders; National Institute of Mental Health FX This study was supported by NIMH grants MH59691 (to Drs. Keller/Yen), MH059929 (to Dr. Birmaher), and MH59977 (to Dr. Strober). Dr. Hunt is a senior editor of Brown Child and Adolescent psychopharmacology update, and receives honoraria from Wiley Publishers. Dr. T. Goldstein receives royalties from Guilford Press. Dr. B. Goldstein is a consultant for BMS, has received research support from Pfizer, and has received speaker's honoraria from Purdue Pharma. Dr. Strober receives support from the Resnick Endowed Chair in Eating Disorders. Dr. Birmaher has received research support from the National Institute of Mental Health. He receives royalties from Random House, Inc., and Lippincott Williams & Wilkins. Dr. Keller receives research support from Pfizer, and has received honoraria from Medtronic. Drs. Yen, Frazier, Weinstock, Topor, Ryan, Heather Hower, and Mary Kay Gill report no declarations of interest. NR 82 TC 5 Z9 5 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD OCT PY 2015 VL 132 IS 4 BP 270 EP 280 DI 10.1111/acps.12415 PG 11 WC Psychiatry SC Psychiatry GA CT0UQ UT WOS:000362513200007 PM 25865120 ER PT J AU Ozburn, AR Janowsky, AJ Crabbe, JC AF Ozburn, Angela R. Janowsky, Aaron J. Crabbe, John C. TI Commonalities and Distinctions Among Mechanisms of Addiction to Alcohol and Other Drugs SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Alcohol; Cocaine; Drugs of Abuse; Animal Models; Addiction ID CONTEXT-INDUCED REINSTATEMENT; NUCLEUS-ACCUMBENS SHELL; COCAINE-SEEKING BEHAVIOR; AMINE-ASSOCIATED RECEPTOR-1; CUE-INDUCED REINSTATEMENT; MEDIAL PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA; INTERMITTENT ETHANOL EXPOSURE; DOPAMINE D-1-FAMILY RECEPTORS; SELF-ADMINISTRATION MODEL AB BackgroundAlcohol abuse is comorbid with abuse of many other drugs, some with similar pharmacology and others quite different. This leads to the hypothesis of an underlying, unitary dysfunctional neurobiological basis for substance abuse risk and consequences. MethodsIn this review, we discuss commonalities and distinctions of addiction to alcohol and other drugs. We focus on recent advances in preclinical studies using rodent models of drug self-administration. ResultsWhile there are specific behavioral and molecular manifestations common to alcohol, psychostimulant, opioid, and nicotine dependence, attempts to propose a unifying theory of the addictions inevitably face details where distinctions are found among classes of drugs. ConclusionsFor alcohol, versus other drugs of abuse, we discuss and compare advances in: (i) neurocircuitry important for the different stages of drug dependence; (ii) transcriptomics and genetical genomics; and (iii) enduring effects, noting in particular the contributions of behavioral genetics and animal models. C1 [Ozburn, Angela R.; Janowsky, Aaron J.; Crabbe, John C.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA. [Ozburn, Angela R.; Janowsky, Aaron J.; Crabbe, John C.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Sch Med, Portland, OR 97201 USA. [Ozburn, Angela R.; Crabbe, John C.] Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97201 USA. [Janowsky, Aaron J.] Oregon Hlth & Sci Univ, Dept Psychiat, Sch Med, Portland, OR 97201 USA. [Janowsky, Aaron J.] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97201 USA. RP Ozburn, AR (reprint author), 3181 SW Sam Jackson Pk Rd L470, Portland, OR 97239 USA. EM ozburn@ohsu.edu FU BLRD VA [I01 BX000313, I01 BX002758, IK2 BX002488]; NIAAA NIH HHS [P60 AA010760, AA020245, AA10760, AA13519, P50 AA010760, R24 AA020245, U01 AA013519]; NIDA NIH HHS [P50 DA018165] NR 176 TC 3 Z9 3 U1 5 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2015 VL 39 IS 10 BP 1863 EP 1877 DI 10.1111/acer.12810 PG 15 WC Substance Abuse SC Substance Abuse GA CS9OI UT WOS:000362420100002 PM 26431116 ER PT J AU Cummings, DE AF Cummings, David E. TI Taste and the regulation of food intake: it's not just about flavor SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID LIPIDS C1 [Cummings, David E.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Cummings, David E.] Univ Washington, Sch Med, Diabet & Obes Ctr Excellence, Seattle, WA USA. RP Cummings, DE (reprint author), Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM davidec@u.washington.edu FU NIDDK NIH HHS [DK084324, DK089528, DK103842] NR 10 TC 6 Z9 6 U1 0 U2 5 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 OCT PY 2015 VL 102 IS 4 BP 717 EP 718 DI 10.3945/ajcn.115.120667 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CS7CO UT WOS:000362241900001 PM 26354541 ER PT J AU Gaskins, AJ Chiu, YH Williams, PL Ford, JB Toth, TL Hauser, R Chavarro, JE AF Gaskins, Audrey J. Chiu, Yu-Han Williams, Paige L. Ford, Jennifer B. Toth, Thomas L. Hauser, Russ Chavarro, Jorge E. CA EARTH Study Team TI Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE assisted reproduction; folate; infertility; vitamin B-12; pregnancy; in vitro fertilization ID FOLIC-ACID SUPPLEMENTATION; IN-VITRO FERTILIZATION; DIETARY-FOLATE; UNITED-STATES; INFERTILITY; PREGNANCY; HOMOCYSTEINE; BIOMARKERS; COUNTRIES; SUCCESS AB Background: Preconceptional folate and vitamin B-12 have been linked to beneficial reproductive outcomes in both natural pregnancies and those after assisted reproductive technology (ART) treatment. Objective: The objective of the study was to evaluate the associations of serum folate and vitamin B-12 with ART outcomes. Design: This analysis included a random sample of 100 women (154 ART cycles) participating in a prospective cohort study [Environment and Reproductive Health (EARTH)] at the Massachusetts General Hospital Fertility Center (2007-2013). Serum folate and vitamin B-12 were measured in blood samples collected between days 3 and 9 of treatment. Generalized estimating equations with adjustment for age, BMI, and race were used to evaluate the association of serum folate and vitamin B-12 with ART outcomes. Results: Women in the highest quartile of serum folate (>26.3 ng/mL) had 1.62 (95% CI: 0.99, 2.65) times the probability of live birth compared with women in the lowest quartile (<16.6 ng/mL). Women in the highest quartile of serum vitamin B-12 (>701 pg/mL) had 2.04 (95% CI: 1.14, 3.62) times the probability of live birth compared with women in the lowest quartile (<439 pg/mL). Suggestive evidence of an interaction was observed; women with serum folate and vitamin B-12 concentrations greater than the median had 1.92 (95% CI: 1.12, 3.29) times the probability of live birth compared with women with folate and vitamin B-12 concentrations less than or equal to the median. This translated into an adjusted difference in live birth rates of 26% (95% CI: 10%, 48%; P = 0.02). Conclusion: Higher serum concentrations of folate and vitamin B-12 before ART treatment were associated with higher live birth rates among a population exposed to folic acid fortification. C1 [Gaskins, Audrey J.; Chiu, Yu-Han; Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Williams, Paige L.; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ford, Jennifer B.; Hauser, Russ] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Toth, Thomas L.; Hauser, Russ] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Toth, Thomas L.; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Sch Med, Boston, MA USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Gaskins, AJ (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM agaskins@hsph.harvard.edu FU NIH from National Institute of Environmental Health Sciences [R01-ES009718]; NIH grant from the National Institute of Diabetes and Digestive and Kidney Diseases [P30-DK046200, T32-DK007703-16] FX Supported by NIH grants R01-ES009718 from the National Institute of Environmental Health Sciences and P30-DK046200 and T32-DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 36 TC 6 Z9 6 U1 0 U2 4 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 OCT PY 2015 VL 102 IS 4 BP 943 EP 950 DI 10.3945/ajcn.115.112185 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CS7CO UT WOS:000362241900027 PM 26354529 ER PT J AU Russo, S Blackstock, AW Herman, JM Abdel-Wahab, M Azad, N Das, P Goodman, KA Hong, TS Jabbour, SK Jones, WE Konski, AA Koong, AC Kumar, R Rodriguez-Bigas, M Small, W Thomas, CR Suh, WW AF Russo, Suzanne Blackstock, A. William Herman, Joseph M. Abdel-Wahab, May Azad, Nilofer Das, Prajnan Goodman, Karyn A. Hong, Theodore S. Jabbour, Salma K. Jones, William E., III Konski, Andre A. Koong, Albert C. Kumar, Rachit Rodriguez-Bigas, Miguel Small, William, Jr. Thomas, Charles R., Jr. Suh, W. Warren TI ACR Appropriateness Criteria (R) Local Excision in Early Stage Rectal Cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE early stage rectal cancer; local excision; adjuvant; neoadjuvant; Appropriateness Criteria ID TRANSANAL ENDOSCOPIC MICROSURGERY; TOTAL MESORECTAL EXCISION; RADIATION-THERAPY; NEOADJUVANT CHEMORADIATION; FOLLOW-UP; PREOPERATIVE CHEMORADIATION; STANDARD RESECTION; DISTAL RECTUM; T1; RECURRENCE AB Low anterior resection or abdominoperineal resection are considered standard treatments for early rectal cancer but may be associated with morbidity in selected patients who are candidates for early distal lesions amenable to local excision (LE). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel recognizes the importance of accurate staging to identify patients who may be candidates for a LE approach. Patients who may be candidates for LE alone include those with small, low-lying T1 tumors, without adverse pathologic features. Several surgical approaches can be utilized for LE however none include lymph node evaluation. Adjuvant radiation +/- chemotherapy may be warranted depending on the risk of nodal metastases. Patients with high-risk T1 tumors, T2 tumors not amenable to radical surgery may also benefit from adjuvant treatment; however, patients with positive margins or T3 lesions should be offered abdominoperineal resection or low anterior resection. Neoadjuvant radiation +/- chemotherapy followed by LE in higher risk patients results in excellent local control, but it is not clear if this approach reduces recurrence rates over surgery alone. C1 [Russo, Suzanne] Univ Hosp Case Western, Seidman Canc Ctr, Dept Radiat Oncol, Cleveland, OH 44106 USA. [Blackstock, A. William] Wake Forest Univ, Dept Radiat Oncol, Winston Salem, NC 27109 USA. [Herman, Joseph M.; Azad, Nilofer] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Herman, Joseph M.; Azad, Nilofer] Amer Soc Clin Oncol, Alexandria, VA USA. [Abdel-Wahab, May] Cleveland Clin, Cleveland, OH 44106 USA. [Das, Prajnan] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Das, Prajnan] Amer Coll Surg, Chicago, IL USA. [Goodman, Karyn A.; Rodriguez-Bigas, Miguel] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hong, Theodore S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jabbour, Salma K.] Rutgers State Univ, Rutgers Canc Inst New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA. [Jones, William E., III] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Konski, Andre A.] Chester Cty Hosp, W Chester, PA USA. [Koong, Albert C.] Stanford Univ, Med Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA. [Kumar, Rachit] Johns Hopkins Univ, Dept Radiat Oncol, Baltimore, MD USA. [Small, William, Jr.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Suh, W. Warren] Canc Ctr Santa Barbara, Santa Barbara, CA USA. RP Russo, S (reprint author), Univ Hosp Case Western, Seidman Canc Ctr, Dept Radiat Oncol, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM Suzanne.Russo@UHhospitals.org FU Genentech FX J.M.H.: Nucletron and Genentech. P.D.: Research support from Genentech. The other authors declare no conflicts of interest. NR 74 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 2015 VL 38 IS 5 BP 520 EP 525 DI 10.1097/COC.0000000000000197 PG 6 WC Oncology SC Oncology GA CT0VD UT WOS:000362514600014 PM 26371522 ER PT J AU Steensma, DP Dakhil, SR Novotny, PJ Sloan, JA Johnson, DB Anderson, DM Mattar, BI Moore, DF Nikcevich, D Loprinzi, CL AF Steensma, David P. Dakhil, Shaker R. Novotny, Paul J. Sloan, Jeff A. Johnson, David B. Anderson, Daniel M. Mattar, Bassam I. Moore, Dennis F., Jr. Nikcevich, Daniel Loprinzi, Charles L. TI A randomized comparison of once weekly epoetin alfa to extended schedule epoetin or darbepoetin in chemotherapy-associated anemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CANCER-RELATED ANEMIA; QUALITY-OF-LIFE; STIMULATING AGENTS; PHASE-III; HEMOGLOBIN; MORTALITY; THERAPY; FATIGUE; DEATH AB Erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients with cancer chemotherapy-associated anemia (CAA). Extended-interval ESA dosing (administration less than once weekly) is common with DA, but previous studies suggested that EA might also be administered less often than weekly. In this multicenter prospective trial, 239 CAA patients with Hb <10.5 g/dL were randomized to receive EA 40,000 U subcutaneously once weekly ("40K" arm), EA 80,000 U every 3 weeks ("80K"), EA 120,000 U every 3 weeks ("120K"arm), or DA 500 mcg every 3 weeks ("DA"), for 15 weeks. The primary endpoint was the proportion of patients achieving Hb >= 11.5 g/dL or increment of Hb > 2.0 g/dL from baseline without transfusion. Secondary endpoints included transfusion requirements, adverse events (AEs), and patient-reported outcomes (PROs). There were no significant differences between treatment arms in the proportion of patients achieving Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; P > 0.41 for all comparisons) or requiring RBC transfusion, but the median Hb increment from baseline was higher in the 40K and DA arms compared to the two extended dosing EA arms, and Hb response was achieved soonest in the weekly EA arm. There were no differences in PROs or AEs. The FDA-approved schedules tested-weekly EA 40,000 U, and every 3 week DA 500 mcg-are reasonable standards for CAA therapy. (C) 2015 Wiley Periodicals, Inc. C1 [Steensma, David P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Dakhil, Shaker R.; Johnson, David B.; Mattar, Bassam I.; Moore, Dennis F., Jr.] Canc Ctr Kansas, Wichita, KS USA. [Novotny, Paul J.; Sloan, Jeff A.] Mayo Clin, Canc Ctr Stat, Rochester, MN USA. [Anderson, Daniel M.] Minnesota CGOP, St Paul, MN USA. [Nikcevich, Daniel] St Marys Duluth Clin, Duluth, MN USA. [Loprinzi, Charles L.] Mayo Clin, Dept Oncol, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Ave,D2037, Boston, MA 02215 USA. EM dsteensma@partners.org FU Mayo Clinic Cancer Research Consortium (Academic and Community Cancer Research United, ACCRU); Janssen; Henry J. Predolin Foundation FX Contract grant sponsors: Mayo Clinic Cancer Research Consortium (Academic and Community Cancer Research United, ACCRU), and Centocor Ortho Biotech, a division of Johnson & Johnson (now Janssen); Contract grant sponsor: Henry J. Predolin Foundation (to D.P.S.). NR 32 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2015 VL 90 IS 10 BP 877 EP 881 DI 10.1002/ajh.24110 PG 5 WC Hematology SC Hematology GA CT2VV UT WOS:000362663900011 PM 26149465 ER PT J AU Vilhjalmsson, BJ Yang, J Finucane, HK Gusev, A Lindstrom, S Ripke, S Genovese, G Loh, PR Bhatia, G Do, R Hayeck, T Won, HH Kathiresan, S Pato, M Pato, C Tamimi, R Stahl, E Zaitlen, N Pasaniuc, B Belbin, G Kenny, EE Schierup, MH De Jager, P Patsopouos, NA Mc Carroll, S Daly, M Purce, S Chasman, D Neale, B Goddard, M Visscher, PM Kraft, P Patterson, N Price, AL AF Vilhjalmsson, Bjarni J. Yang, Jian Finucane, Hilary K. Gusev, Alexander Lindstrom, Sara Ripke, Stephan Genovese, Giulio Loh, Po-Ru Bhatia, Gaurav Do, Ron Hayeck, Tristan Won, Hong-Hee Kathiresan, Sekar Pato, Michele Pato, Carlos Tamimi, Rulla Stahl, Eli Zaitlen, Noah Pasaniuc, Bogdan Belbin, Gillian Kenny, Eimear E. Schierup, Mikkel H. De Jager, Philip Patsopouos, Nikolaos A. Mc Carroll, Steve Daly, Mark Purce, Shaun Chasman, Daniel Neale, Benjamin Goddard, Michael Visscher, Peter M. Kraft, Peter Patterson, Nick Price, Alkes L. CA Psychiat Genomics Consortium Discovery Biol Risk Inherited TI Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ANALYSIS IDENTIFIES 13; BREAST-CANCER RISK; SUSCEPTIBILITY LOCI; COMPLEX TRAITS; MULTIPLE-SCLEROSIS; GENETIC-RISK; MIXED-MODEL; PREDICTION; SCHIZOPHRENIA AB Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R-2 increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase. C1 [Vilhjalmsson, Bjarni J.; Yang, Jian; Finucane, Hilary K.; Lindstrom, Sara; Loh, Po-Ru; Bhatia, Gaurav; Hayeck, Tristan; Tamimi, Rulla; Kraft, Peter; Price, Alkes L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Vilhjalmsson, Bjarni J.; Finucane, Hilary K.; Gusev, Alexander; Lindstrom, Sara; Loh, Po-Ru; Bhatia, Gaurav; Hayeck, Tristan; Tamimi, Rulla; Kraft, Peter; Price, Alkes L.] Harvard Univ, TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [Vilhjalmsson, Bjarni J.; Finucane, Hilary K.; Gusev, Alexander; Genovese, Giulio; Loh, Po-Ru; Bhatia, Gaurav; Hayeck, Tristan; Won, Hong-Hee; Kathiresan, Sekar; Stahl, Eli; De Jager, Philip; Patsopouos, Nikolaos A.; Mc Carroll, Steve; Daly, Mark; Purce, Shaun; Neale, Benjamin; Kraft, Peter; Patterson, Nick; Price, Alkes L.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Finucane, Hilary K.] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus, Denmark. [Yang, Jian; Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Yang, Jian; Finucane, Hilary K.; Visscher, Peter M.] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4101, Australia. [Ripke, Stephan; Genovese, Giulio; Mc Carroll, Steve; Daly, Mark; Neale, Benjamin] MIT, Dept Math, Cambridge, MA 02139 USA. [Ripke, Stephan; Genovese, Giulio; Mc Carroll, Steve; Daly, Mark] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ripke, Stephan] Charite, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany. [Genovese, Giulio; Mc Carroll, Steve] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Do, Ron; Kenny, Eimear E.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Stahl, Eli; Kenny, Eimear E.; Purce, Shaun] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Won, Hong-Hee; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Won, Hong-Hee; Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pato, Michele; Pato, Carlos] Univ So Calif, Dept Psychiat & Behav Sci, Keck Sch Med, Los Angeles, CA 90089 USA. [Tamimi, Rulla] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Stahl, Eli; Purce, Shaun] Icahn Sch Med Mt Sinai, Div Psychiat Genom, New York, NY 10029 USA. [Stahl, Eli; Kenny, Eimear E.; Purce, Shaun] Icahn Sch Med Mt Sinai, Ctr Stat Genet, New York, NY 10029 USA. [Zaitlen, Noah] Univ Calif San Francisco, Lung Biol Ctr, Dept Med, San Francisco, CA 94143 USA. [Pasaniuc, Bogdan] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Kenny, Eimear E.] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA. [De Jager, Philip; Patsopouos, Nikolaos A.; Chasman, Daniel] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [De Jager, Philip; Patsopouos, Nikolaos A.] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Ann Romney Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. [Chasman, Daniel] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Goddard, Michael] Univ Melbourne, Dept Food & Agr Syst, Parkville, Vic 3010, Australia. [Goddard, Michael] Dept Primary Ind, Biosci Res Div, Bundoora, Vic 3083, Australia. [Kraft, Peter; Price, Alkes L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Vilhjalmsson, BJ (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM bjami.vilhjalmsson@gmail.com; aprice@hsph.harvard.edu RI Stroup, Thomas/F-9188-2014; Collier, David/D-1649-2011; Mattheisen, Manuel/B-4949-2012; Slominsky, Petr/B-4640-2016; Hammer, Christian/C-5827-2014; Pantelis, Christos/H-7722-2014; Ruderfer, Douglas/M-5795-2016; Webb, Bradley/B-1459-2009; McQuillin, Andrew/C-1623-2008; Yang, Jian/A-5852-2010; Melle, Ingrid /B-4858-2011; Domenici, Enrico/K-8194-2016; Schierup, Mikkel/F-1675-2010; Hansen, Thomas Folkmann/O-5965-2014; OI Gill, Michael/0000-0003-0206-5337; Grove, Jakob/0000-0003-2284-5744; Corvin, Aiden/0000-0001-6717-4089; Agartz, Ingrid/0000-0002-9839-5391; Golimbet, Vera/0000-0002-9960-7114; Crowley, James/0000-0001-9051-1557; Stroup, Thomas/0000-0002-3123-0672; Myin-Germeys, Inez/0000-0002-3731-4930; Collier, David/0000-0003-4087-1559; Mattheisen, Manuel/0000-0002-8442-493X; Slominsky, Petr/0000-0003-3530-0655; Hammer, Christian/0000-0003-4548-7548; Pantelis, Christos/0000-0002-9565-0238; Ruderfer, Douglas/0000-0002-2365-386X; Webb, Bradley/0000-0002-0576-5366; McQuillin, Andrew/0000-0003-1567-2240; Golimbet, Vera/0000-0002-0114-4300; Yang, Jian/0000-0003-2001-2474; Melle, Ingrid /0000-0002-9783-548X; Domenici, Enrico/0000-0001-7436-6919; Schierup, Mikkel/0000-0002-5028-1790; Escott-Price, Valentina/0000-0003-1784-5483; Murphy, Kieran/0000-0003-2930-4465; Julia Cano, Antonio/0000-0001-6064-3620; Hansen, Thomas Folkmann/0000-0001-6703-7762; Mortensen, Preben Bo/0000-0002-5230-9865; Moran, Jennifer/0000-0002-5664-4716; Walters, James/0000-0002-6980-4053; Suvisaari, Jaana/0000-0001-7167-0990; Buxbaum, Joseph/0000-0001-8898-8313; Bruggeman, Richard/0000-0002-3238-8471; O'Neill, Francis Anthony/0000-0002-7531-7657; /0000-0002-8114-7615; McIntosh, Andrew/0000-0002-0198-4588; Dinan, Timothy/0000-0002-2316-7220; Adolfsson, Rolf/0000-0001-9785-8473; dos Santos Silva, Isabel/0000-0002-6596-8798; Donohoe, Gary/0000-0003-3037-7426; murray, robin/0000-0003-0829-0519; Visscher, Peter/0000-0002-2143-8760; Knight, Joanne/0000-0002-7148-1660 FU NIH [R01 GM105857, R03 CA173785, U19 CA148065-01]; Danish Council for Independent Research [DFF-1325-0014]; Fannie and John Hertz Foundation; Wellcome Trust [076113] FX We thank Shamil Sunayev, Brendan Bulik-Sullivan, Liming Liang, Naomi Wray, Daniel Sorensen, and Esben Agerbo for useful discussions. We would also like to thank Toni Clarke for useful comments on the software. This research was supported by NIH grants R01 GM105857, R03 CA173785, and U19 CA148065-01. B.J.V. was supported by Danish Council for Independent Research grant DFF-1325-0014. H.K.F. was supported by the Fannie and John Hertz Foundation. This study made use of data generated by the Wellcome Trust Case Control Consortium (WTCCC) and the Wellcome Trust Sanger Institute. A full list of the investigators who contributed to the generation of the WTCCC data is available at www.wtccc.org.uk. Funding for the WTCCC project was provided by the Wellcome Trust under award 076113. NR 64 TC 27 Z9 27 U1 2 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT 1 PY 2015 VL 97 IS 4 BP 576 EP 592 DI 10.1016/j.ajhg.2015.09.001 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA CT2FL UT WOS:000362617300008 PM 26430803 ER PT J AU Castleberry, AW Englum, BR Snyder, LD Worni, M Osho, AA Gulack, BC Palmer, SM Davis, RD Hartwig, MG AF Castleberry, Anthony W. Englum, Brian R. Snyder, Laurie D. Worni, Mathias Osho, Asishana A. Gulack, Brian C. Palmer, Scott M. Davis, R. Duane Hartwig, Matthew G. TI The Utility of Preoperative Six-Minute-Walk Distance in Lung Transplantation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE lung transplantation; exercise tolerance; patient outcome assessment ID PRIMARY PULMONARY-HYPERTENSION; LONG-TERM SURVIVAL; WALK TEST; POSTOPERATIVE COMPLICATIONS; REFERENCE EQUATIONS; CURATIVE RESECTION; SURGICAL-PATIENTS; MAJOR SURGERY; UNITED-STATES; MORTALITY AB Rationale: The use of 6-minute-walk distance (6MWD) as an indicator of exercise capacity to predict postoperative survival in lung transplantation has not previously been well studied. Objectives: To evaluate the association between 6MWD and postoperative survival following lung transplantation. Methods: Adult, first time, lung-only transplantations per the United Network for Organ Sharing database from May 2005 to December 2011 were analyzed. Kaplan-Meier methods and Cox proportional hazards modeling were used to determine the association between preoperative 6MWD and post-transplant survival after adjusting for potential confounders. A receiver operating characteristic curve was used to determine the 6MWD value that provided maximal separation in 1-year mortality. A subanalysis was performed to assess the association between 6MWD and post-transplant survival by disease category. Measurements and Main Results: A total of 9,526 patients were included for analysis. The median 6MWD was 787 ft (25th-75th percentiles = 450-1,082 ft). Increasing 6MWD was associated with significantly lower overall hazard of death (P < 0.001). Continuous increase in walk distance through 1,200-1,400 ft conferred an incremental survival advantage. Although 6MWD strongly correlated with survival, the impact of a single dichotomous value to predict outcomes was limited. All disease categories demonstrated significantly longer survival with increasing 6MWD (P <= 0.009) except pulmonary vascular disease (P = 0.74); however, the low volume in this category (n = 312; 3.3%) may limit the ability to detect an association. Conclusions: 6MWD is significantly associated with post-transplant survival and is best incorporated into transplant evaluations on a continuous basis given limited ability of a single, dichotomous value to predict outcomes. C1 [Castleberry, Anthony W.; Englum, Brian R.; Worni, Mathias; Gulack, Brian C.; Davis, R. Duane; Hartwig, Matthew G.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Castleberry, Anthony W.; Davis, R. Duane; Hartwig, Matthew G.] Duke Univ, Med Ctr, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA. [Snyder, Laurie D.; Palmer, Scott M.] Duke Univ, Med Ctr, Div Pulm & Crit Care, Durham, NC 27710 USA. [Englum, Brian R.] Duke Clin Res Inst, Durham, NC USA. [Worni, Mathias] Univ Bern, Inselspital, Dept Visceral Surg & Med, CH-3010 Bern, Switzerland. [Osho, Asishana A.] Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. RP Castleberry, AW (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 3443 Med Ctr, Durham, NC 27710 USA. EM anthony.castleberry@duke.edu FU Health Resources and Services Administration [234-2005-370011C] FX By use of the UNOS database, this work was supported in part by Health Resources and Services Administration contract 234-2005-370011C. The content herein is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 41 TC 5 Z9 5 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2015 VL 192 IS 7 BP 843 EP 852 DI 10.1164/rccm.201409-1698OC PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CT3GK UT WOS:000362695000014 PM 26067395 ER PT J AU Soon, E Crosby, A Southwood, M Yang, P Tajsic, T Toshner, M Appleby, S Shanahan, CM Bloch, KD Pepke-Zaba, J Upton, P Morrell, NW AF Soon, Elaine Crosby, Alexi Southwood, Mark Yang, Peiran Tajsic, Tamara Toshner, Mark Appleby, Sarah Shanahan, Catherine M. Bloch, Kenneth D. Pepke-Zaba, Joanna Upton, Paul Morrell, Nicholas W. TI Bone Morphogenetic Protein Receptor Type II Deficiency and Increased Inflammatory Cytokine Production SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE pulmonary hypertension; bone morphogenetic protein receptor type II; cytokine; lipopolysaccharide; inflammation ID PULMONARY ARTERIAL-HYPERTENSION; EXTRACELLULAR-SUPEROXIDE DISMUTASE; SMOOTH-MUSCLE; TGF-BETA; SYSTEMIC-SCLEROSIS; HETEROZYGOUS MICE; MOUSE MODEL; INTERLEUKIN-6; EXPRESSION; HYPOXIA AB Rationale: Mutations in bone morphogenetic protein receptor type II (BMPR-II) underlie most cases of heritable pulmonary arterial hypertension (PAH). However, disease penetrance is only 20-30%, suggesting a requirement for additional triggers. Inflammation is emerging as a key disease-related factor in PAH, but to date there is no clear mechanism linking BMPR-II deficiency and inflammation. Objectives: To establish a direct link between BMPR-II deficiency, a consequentially heightened inflammatory response, and development of PAH. Methods: We used pulmonary artery smooth muscle cells from Bmpr2(+/-) mice and patients with BMPR2 mutations and compared them with wild-type controls. For the in vivo model, we used mice heterozygous for a null allele in Bmpr2 (Bmpr2(+/-)) and wild-type littermates. Measurements and Main Results: Acute exposure to LPS increased lung and circulating IL-6 and KC (IL-8 analog) levels in Bmpr2(+/-) mice to a greater extent than in wild-type controls., Similarly, pulmonary artery smooth muscle cells from Bmpr2(+/) mice and patients with BMPR2 mutations produced higher levels of IL-6 and KC/IL-8 after lipopolysaccharide stimulation compared with controls. BMPR-II deficiency in mouse and human pulmonary artery smooth muscle cells was associated with increased phospho-STAT3 and loss of extracellular superoxide dismutase. Chronic lipopolysaccharide administration caused pulmonary hypertension in Bmpr2(+/-) mice but not in wild-type littermates. Coadministration of tempol, a superoxide dismutase mimetic, ameliorated the exaggerated inflammatory response and prevented development of PAH. Conclusions: This study demonstrates that BMPR-II deficiency promotes an exaggerated inflammatory response in vitro and in vivo, which can instigate development of pulmonary hypertension. C1 [Soon, Elaine; Crosby, Alexi; Yang, Peiran; Tajsic, Tamara; Toshner, Mark; Appleby, Sarah; Upton, Paul; Morrell, Nicholas W.] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Dept Med, Cambridge CB2 0QQ, England. [Soon, Elaine; Southwood, Mark; Pepke-Zaba, Joanna] Papworth Hosp, Pulm Vasc Dis Unit, Cambridge CB3 8RE, England. [Tajsic, Tamara; Shanahan, Catherine M.] Kings Coll London, Cardiovasc Div, James Black Ctr, London WC2R 2LS, England. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Morrell, NW (reprint author), Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Dept Med, Box 157,Hills Rd, Cambridge CB2 0QQ, England. EM nwm23@cam.ac.uk FU Medical Research Council training fellowship; Sackler scholarship; Wellcome Trust fellowship; National Institute for Health Research (NIHR) Healthcare Scientist fellowship; Fondation Leducq network award; British Heart Foundation program grant FX Supported by a Medical Research Council training fellowship and Sackler scholarship to E.S., a Wellcome Trust fellowship to P.Y., a National Institute for Health Research (NIHR) Healthcare Scientist fellowship to M.S., a British Heart Foundation program grant to N.W.M., and a Fondation Leducq network award to K.D.B. and N.W.M. Infrastructure support was provided by the Cambridge NIHR Biomedical Research Centre. NR 61 TC 15 Z9 15 U1 1 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2015 VL 192 IS 7 BP 859 EP 872 DI 10.1164/rccm.201408-1509OC PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CT3GK UT WOS:000362695000016 PM 26073741 ER PT J AU Taber, DJ Pilch, NA Trofe-Clark, J Kaiser, TE AF Taber, D. J. Pilch, N. A. Trofe-Clark, J. Kaiser, T. E. TI A National Survey Assessing the Current Workforce of Transplant Pharmacists Across Accredited US Solid Organ Transplant Programs SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID UNITED-STATES; PATIENT-CARE; RECIPIENTS; ADHERENCE; SERVICES; TEAM; FAILURE; CENTERS AB Integration of pharmacists into multidisciplinary transplant patient care has advanced in recent years, with limited data available to evaluate the current status of the profession. This was a national survey developed as an AST Pharmacy COP initiative. Responses were solicited from pharmacists practicing at U.S. transplant programs based on UNOS listing; 176 participants from 113 centers (41%) responded, with 79% practicing <= 10 years. There is a median of 1.4 pharmacist full-time equivalents (FTEs) (range 0.1-7.1) for every 100 transplants. The predominant activities performed by pharmacists during the transplant phase include medication review (95%), lab review (92%), allergy review (88%), medication therapy management (92%), bedside rounds (87%), medication education (79%), documentation (71%), and coordinating discharge medications (58%). Similar activities were reported during the other phases, but participation was less common. The involvement of dedicated transplant pharmacists within multidisciplinary care has become standard at a large number of centers, although expansion is still needed to ensure core pharmaceutical care components are provided to all transplant recipients across all centers. These results inform on the typical responsibilities of pharmacists practicing within the field of transplantation and illustrate that the level of pharmacist involvement significantly varies across transplant centers and the phases of transplantation. C1 [Taber, D. J.] Ralph H Johnson VA Med Ctr, Dept Pharm, Charleston, SC 29401 USA. [Taber, D. J.] Med Univ S Carolina, Div Transplant Surg, Charleston, SC 29425 USA. [Pilch, N. A.] Med Univ S Carolina, Dept Pharm Serv, Charleston, SC 29425 USA. [Trofe-Clark, J.] Hosp Univ Penn, Dept Pharm Serv, Philadelphia, PA 19104 USA. [Trofe-Clark, J.] Univ Penn, Perelman Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Kaiser, T. E.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. RP Taber, DJ (reprint author), Ralph H Johnson VA Med Ctr, Dept Pharm, Charleston, SC 29401 USA. EM taberd@musc.edu FU South Carolina Clinical and Translational (SCTR) Institute [NIH/NCATS UL1TR000062] FX Survey development, dissemination and reporting were supported by the South Carolina Clinical and Translational (SCTR) Institute through grant no. NIH/NCATS UL1TR000062. The authors wish to thank the following people for their efforts with the design, analysis and interpretation of this endeavor: Additional Workforce Committee Members: Clark Benedetti, Drew Silverman, Eric Tichy, Jeong Park, Karen Hardinger, Mark Baillie, Spencer Martin, and Travis Dick. Survey Development and Review: Mark Baillie, Jeong Park, and Travis Dick. Survey Piloting: Karen Hardinger, Winston Ally, and Jeong Park. Manuscript Review: Samir Patel, Eric Tichy, Barrett Crowther, Rita Alloway, Lisa McDevitt, and Christin Rogers. NR 22 TC 3 Z9 3 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2015 VL 15 IS 10 BP 2683 EP 2690 DI 10.1111/ajt.13323 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA CT2WJ UT WOS:000362665400020 PM 25988533 ER PT J AU Lei, J Kim, JI Shi, S Zhang, X Machaidze, Z Lee, S Schuetz, C Martins, PN Oura, T Farkash, EA Rosales, IA Smith, RN Stott, R Lee, KM Soohoo, J Boskovic, S Cappetta, K Nadazdin, OM Yamada, Y Yeh, H Kawai, T Sachs, DH Benichou, G Markmann, JF AF Lei, J. Kim, J. I. Shi, S. Zhang, X. Machaidze, Z. Lee, S. Schuetz, C. Martins, P. N. Oura, T. Farkash, E. A. Rosales, I. A. Smith, R. N. Stott, R. Lee, K. M. Soohoo, J. Boskovic, S. Cappetta, K. Nadazdin, O. M. Yamada, Y. Yeh, H. Kawai, T. Sachs, D. H. Benichou, G. Markmann, J. F. TI Pilot Study Evaluating Regulatory T Cell-Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID DENDRITIC CELLS; GRAFT-SURVIVAL; SPLENOCYTE INFUSIONS; CYNOMOLGUS MONKEYS; PANCREATIC-ISLETS; IN-VITRO; TOLERANCE; TRANSPLANTATION; INDUCTION; THERAPY AB The full potential of islet transplantation will only be realized through the development of tolerogenic regimens that obviate the need for maintenance immunosuppression. Here, we report an immunotherapy regimen that combines 1-ethyl-3-(3'-dimethylamino-propyl)-carbodiimide (ECDI)-treated donor lymphoid cell infusion (ECDI-DLI) with thymoglobulin, anti-interleukin-6 receptor antibody and rapamycin to achieve prolonged allogeneic islet graft survival in a nonhuman primate (NHP) model. Prolonged graft survival is associated with Treg expansion, donor-specific T cell hyporesponsiveness and a transient absence of donor-specific alloantibody production during the period of graft survival. This regimen shows promise for clinical translation. C1 [Lei, J.; Kim, J. I.; Shi, S.; Zhang, X.; Machaidze, Z.; Lee, S.; Schuetz, C.; Martins, P. N.; Oura, T.; Stott, R.; Lee, K. M.; Soohoo, J.; Boskovic, S.; Cappetta, K.; Nadazdin, O. M.; Yamada, Y.; Yeh, H.; Kawai, T.; Sachs, D. H.; Benichou, G.; Markmann, J. F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA 02138 USA. [Farkash, E. A.; Rosales, I. A.; Smith, R. N.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Markmann, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA 02138 USA. EM Jlei2@mgh.harvard.edu; jmarkmann@mgh.harvard.edu RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 FU NIH [R00000000004607, R00000000002176, 5U19A1051731-10]; NIH-NIDDK [5K08DK094965-03]; NIAID/NIDDK Nonhuman Primate Transplantation Tolerance Cooperative Studies Group FX This work was supported in part by NIH grant: R00000000004607 to Emory University (ID: R00000000002176). Sub-award to Massachusetts General Hospital, J.F.M./D.H.S. (NIH 5U19A1051731-10) and NIH-NIDDK: 5K08DK094965-03 to H.Y. We also acknowledge the support of the NIAID/NIDDK Nonhuman Primate Transplantation Tolerance Cooperative Studies Group. NR 30 TC 1 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2015 VL 15 IS 10 BP 2739 EP 2749 DI 10.1111/ajt.13329 PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA CT2WJ UT WOS:000362665400027 PM 26014796 ER PT J AU Leung, DT Das, SK Malek, MA Qadri, F Faruque, ASG Chisti, MJ Ryan, ET AF Leung, Daniel T. Das, Sumon K. Malek, M. A. Qadri, Firdausi Faruque, A. S. G. Chisti, Mohammod J. Ryan, Edward T. TI Concurrent Pneumonia in Children under 5 Years of Age Presenting to a Diarrheal Hospital in Dhaka, Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID SEVERELY MALNOURISHED CHILDREN; COMMUNITY-ACQUIRED PNEUMONIA; DEVELOPING-COUNTRIES; INFECTIONS; RISK; CRYPTOSPORIDIOSIS; SURVEILLANCE; TRANSMISSION; PREDICTORS; MORTALITY AB Respiratory and gastrointestinal infections are the top killers of children worldwide, and their co-occurrence is reported but not well understood. Our aim was to determine the risk factors for concurrent presentation of diarrhea and pneumonia (DP) in a resource-limited setting in Bangladesh. We used data from the Diarrheal Disease Surveillance System of the icddr,b Dhaka Hospital to identify children < 60 months of age with diarrhea and concurrent pneumonia, defined as a history of cough, an abnormal lung examination, and tachypnea. For the years 1996-2007, out of total 14,628 diarrheal patients surveyed, there were 607 (4%) patients who satisfied criteria for pneumonia. Those with DP had a higher mortality rate (4% versus 0.05%, odds ratio [OR] = 86, 95% confidence interval [CI] = 26-286) and a longer hospital stay (mean 84 versus 26 hours, difference 58 hours, 95% CI = 52-64 hours) than those with diarrhea (D) only. In multivariable logistic regression comparing cases (N = 607) with controls matched for month and year of admission at a ratio of 1:3 (N = 1,808), we found that DP was associated with younger age, male gender, severe acute malnutrition (SAM), less maternal education, lower family income, and lack of current breast-feeding history. C1 Univ Utah, Sch Med, Div Infect Dis, Dept Med, Salt Lake City, UT 84132 USA. Univ Utah, Sch Med, Div Microbiol & Immunol, Dept Pathol, Salt Lake City, UT 84132 USA. Icddr B, Ctr Vaccine Sci, Dhaka, Bangladesh. Icddr B, CNFS, Dhaka, Bangladesh. Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Leung, DT (reprint author), Univ Utah, Sch Med, Div Infect Dis, 30 N 1900 E,SOM Room 4C416B, Salt Lake City, UT 84132 USA. EM daniel.leung@utah.edu OI leung, daniel/0000-0001-8401-0801 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases [AI058935, AI100023, AI106878, AI077883, AI100923]; Thrasher Research Fund Early Career Award; Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society of Tropical Medicine and Hygiene/Burroughs Wellcome Fund FX This study was supported by grants from the National Institutes of Health, including National Institute of Allergy and Infectious Diseases grants AI058935, AI100023, AI106878, AI077883 (to Edward T. Ryan), AI100923 (to Daniel T. Leung), a Thrasher Research Fund Early Career Award, and a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society of Tropical Medicine and Hygiene/Burroughs Wellcome Fund (both to Daniel T. Leung). NR 27 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2015 VL 93 IS 4 BP 831 EP 835 DI 10.4269/ajtmh.15-0074 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CS8BX UT WOS:000362311800030 PM 26149863 ER PT J AU Blumenthal, KG Shenoy, ES Varughese, CA Hurwitz, S Hooper, DC Banerji, A AF Blumenthal, Kimberly G. Shenoy, Erica S. Varughese, Christy A. Hurwitz, Shelley Hooper, David C. Banerji, Aleena TI Impact of a clinical guideline for prescribing antibiotics to inpatients reporting penicillin or cephalosporin allergy SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID BETA-LACTAM ANTIBIOTICS; HOSPITALIZED-PATIENTS; ADVERSE-REACTIONS; DRUG ALLERGY; CLOSTRIDIUM-DIFFICILE; HISTORY; HYPERSENSITIVITY; KNOWLEDGE; SAFETY; PREVALENCE AB Background: Self-reported penicillin allergy infrequently reflects an inability to tolerate penicillins. Inpatients reporting penicillin allergy receive alternative antibiotics that might be broader spectrum, more toxic, or less effective. Objective: To develop and assess a clinical guideline for the general inpatient provider that directs taking a history and prescribing antibiotics for patients with penicillin or cephalosporin allergy. Methods: A guideline was implemented to assist providers with assessing allergy history and prescribing antibiotics for patients with reported penicillin or cephalosporin allergy. The guideline used a standard 2-step graded challenge or test dose. A quasi-experimental study was performed to assess safety, feasibility, and impact on antibiotic use by comparing treatment 21 months before guideline implementation with 12 months after guideline implementation. Results: Significantly more test doses to beta-lactam antibiotics were performed monthly after vs before guideline implementation (median 14.5, interquartile range 13-16.25, vs 2, interquartile range 1-3.25, P < .001). Seven adverse drug reactions occurred during guideline-driven test doses, with no significant difference in rate (3.9% vs 6.1%, P = .44) or severity (P > .5) between periods. Guideline-driven test doses decreased alternative antimicrobial therapy after the test dose, including vancomycin (68.3% vs 37.2%, P < .001), aztreonam (11.5% vs 0.5%, P < .001), aminoglycosides (6.0% vs 1.1%, P = .004), and fluoro quinolones (15.3% vs 3.3%, P < .001). Conclusion: The implementation of an inpatient antibiotic prescribing guideline for patients with penicillin or cephalosporin allergy was associated with an almost 7-fold increase in the number of test doses to beta-lactams without increased adverse drug reactions. Patients assessed with guideline-driven test doses were observed to have significantly decreased alternative antibiotic exposure. (C) 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Blumenthal, Kimberly G.; Banerji, Aleena] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Blumenthal, Kimberly G.; Shenoy, Erica S.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Blumenthal, Kimberly G.; Shenoy, Erica S.; Hurwitz, Shelley; Hooper, David C.; Banerji, Aleena] Harvard Univ, Sch Med, Boston, MA USA. [Shenoy, Erica S.; Varughese, Christy A.; Hooper, David C.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Shenoy, Erica S.; Hooper, David C.] Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA. [Hurwitz, Shelley] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Varughese, Christy A.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. RP Blumenthal, KG (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Cox 201 Allergy Associates, Boston, MA 02114 USA. EM kblumenthal1@partners.org FU Partners Center of Expertise for Quality and Safety; National Institutes of Health [T32 HL116275] FX This work was supported by the Partners Center of Expertise for Quality and Safety from 2012 through 2014, departmental funds, and the National Institutes of Health (grant T32 HL116275 to K.G.B.). NR 55 TC 13 Z9 13 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD OCT PY 2015 VL 115 IS 4 BP 294 EP + DI 10.1016/j.anai.2015.05.011 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA CS8ZW UT WOS:000362379500009 PM 26070805 ER PT J AU Thoma, B Chan, TM Paterson, QS Milne, K Sanders, JL Lin, M AF Thoma, Brent Chan, Teresa M. Paterson, Quinten S. Milne, Kenneth Sanders, Jason L. Lin, Michelle TI Emergency Medicine and Critical Care Blogs and Podcasts: Establishing an International Consensus on Quality SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID DELPHI; EDUCATION; RESIDENTS; SKILLS; FOAM AB Study objective: This study identified the most important quality indicators for online educational resources such as blogs and podcasts. Methods: A modified Delphi process that included 2 iterative surveys was used to build expert consensus on a previously defined list of 151 quality indicators divided into 3 themes: credibility, content, and design. Aggregate social media indicators were used to identify an expert population of editors from a defined list of emergency medicine and critical care blogs and podcasts. Survey 1 consisted of the quality indicators and a 7-point Likert scale. The mean score for each quality indicator was included in survey 2, which asked participants whether to "include" or "not include" each quality indicator. The cut point for consensus was defined at greater than 70% "include." Results: Eighty-three percent (20/24) of bloggers and 90.9% (20/22) of podcasters completed survey 1 and 90% (18/20) of bloggers and podcasters completed survey 2. The 70% inclusion criteria were met by 44 and 80 quality indicators for bloggers and podcasters, respectively. Post hoc, a 90% cutoff was used to identify a list of 14 and 26 quality indicators for bloggers and podcasters, respectively. Conclusion: The relative importance of quality indicators for emergency medicine blogs and podcasts was determined. This will be helpful for resource producers trying to improve their blogs or podcasts and for learners, educators, and academic leaders assessing their quality. These results will inform broader validation studies and attempts to develop user-friendly assessment instruments for these resources. Copyright (C) 2015 by the American College of Emergency Physicians. C1 [Thoma, Brent] Massachusetts Gen Hosp, Learning Lab, Dept Emergency Med, Boston, MA 02114 USA. [Thoma, Brent] Massachusetts Gen Hosp, Div Med Simulat, Dept Emergency Med, Boston, MA 02114 USA. [Sanders, Jason L.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Thoma, Brent] Univ Saskatchewan, Emergency Med, Saskatoon, SK S7N 0W0, Canada. [Paterson, Quinten S.] Univ Saskatchewan, Coll Med, Saskatoon, SK S7N 0W0, Canada. [Thoma, Brent; Chan, Teresa M.; Sanders, Jason L.; Lin, Michelle] MedEdLIFE Res Collaborat, San Francisco, CA USA. [Chan, Teresa M.] McMaster Univ, Dept Med, Div Emergency Med, Hamilton, ON L8S 4L8, Canada. [Milne, Kenneth] Univ Western Ontario, Div Emergency Med, London, ON N6A 3K7, Canada. [Lin, Michelle] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. RP Thoma, B (reprint author), Massachusetts Gen Hosp, Learning Lab, Dept Emergency Med, Boston, MA 02114 USA. EM brent.thoma@usask.ca OI Chan, Teresa/0000-0001-6104-462X; Thoma, Brent/0000-0003-1124-5786 NR 25 TC 6 Z9 6 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2015 VL 66 IS 4 BP 396 EP 402 DI 10.1016/j.annemergmed.2015.03.002 PG 7 WC Emergency Medicine SC Emergency Medicine GA CS8BT UT WOS:000362311400012 PM 25840846 ER PT J AU Rogus-Pulia, N Churness, K Hind, J Gangnon, R Banaszynski, K Robbins, J AF Rogus-Pulia, Nicole Churness, Kim Hind, Jacqueline Gangnon, Ronald Banaszynski, Kelsey Robbins, JoAnne TI Comparison of Maximal Lingual Pressure Generation During Isometric Gross and Fine Sensorimotor Tasks in Healthy Adults SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Deglutition disorders; Pressure; Rehabilitation; Tongue ID TONGUE STRENGTH; OROPHARYNGEAL DYSPHAGIA; OLDER-ADULTS; EXERCISE; MUSCLE; AGE; INDIVIDUALS; SARCOPENIA; EVOLUTION; ENDURANCE AB Objectives: To (1) compare 2 distinct isometric lingual press tasks, fine sensorimotor versus gross sensorimotor, at multiple sensor locations in relation to age and sex; and (2) provide a normative data set using a lingual-strengthening device. Design: Cohort study. Setting: University. Participants: Healthy men and women (N=71; age range, 21-82y) recruited from the community. Interventions: Participants were stratified by age and sex and divided into 3 age groups. Participants completed, in random order, 2 isometric tasks: (1) fine sensorimotor: tongue press maximally and discreetly against each of 5 sensors; and (2) gross sensorimotor: tongue press maximally against all 5 sensors simultaneously. Main Outcome Measures: Primary outcome was maximum isometric pressure in hectopascals (hPa). Secondary outcomes were time to reach peak pressure (s) and pressure gradient (hPa/s). Results: Maximum pressures were significantly lower in those of older age for both fine and gross sensorimotor lingual tasks (P<.01), with the front and back sensors showing the greatest decline (35% and 45%, respectively). Pressure differences between tasks (P=. 0 12) resulted in the fine sensorimotor task generating higher pressures at the front sensor for all age groups. However, the gross sensorimotor task generated faster maximum pressures at all sensor locations for all age groups. For both sensorimotor tasks, subjects of older age as a whole generated less steep pressure gradients (P<.001). Conclusions: Age-related decline in tongue strength is greater at the anterior and posterior tongue. Results indicate a simpler gross sensorimotor task may be more beneficial for targeting timing as a biomechanical parameter during therapy, and the fine sensorimotor task may be more beneficial for targeting strength. (C) 2015 by the American Congress of Rehabilitation Medicine C1 [Rogus-Pulia, Nicole; Churness, Kim; Hind, Jacqueline; Banaszynski, Kelsey; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Rogus-Pulia, Nicole; Churness, Kim; Hind, Jacqueline; Robbins, JoAnne] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Gastroenterol & Hepatol, Madison, WI USA. [Gangnon, Ronald] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Gangnon, Ronald] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. [Banaszynski, Kelsey] Univ Wisconsin, Dept Nutr, Madison, WI USA. RP Rogus-Pulia, N (reprint author), 2500 Overlook Terrace,Madison GRECC 11G, Madison, WI 53705 USA. EM npulia@wisc.edu FU United States Department of Agriculture [NRI2007-2234] FX Supported by the United States Department of Agriculture (grant no. NRI2007-2234). The views and content expressed in this article are solely the responsibility of the authors and do not necessarily reflect the position, policy, or official views of the Department of Veteran Affairs or the U.S. Government. NR 43 TC 0 Z9 0 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2015 VL 96 IS 10 BP 1785 EP 1794 DI 10.1016/j.apmr.2015.04.024 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CT2GX UT WOS:000362621100006 PM 25986206 ER PT J AU Bogner, HR McClintock, HFD Hennessy, S Kurichi, JE Streim, JE Xie, DW Pezzin, LE Kwong, PL Stineman, MG AF Bogner, Hillary R. McClintock, Heather F. de Vries Hennessy, Sean Kurichi, Jibby E. Streim, Joel. E. Xie, Dawei Pezzin, Liliana E. Kwong, Pui L. Stineman, Margaret G. TI Patient Satisfaction and Perceived Quality of Care Among Older Adults According to Activity Limitation Stages SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Aged; Disabled persons; Medicare; Patient satisfaction; Rehabilitation ID CURRENT BENEFICIARY SURVEY; HEALTH-CARE; MEDICARE BENEFICIARIES; ELDERLY-PEOPLE; DISABILITIES; COMMUNITY; LIFE; HEARING; DEAF AB Objective: To examine whether patient satisfaction and perceived quality of medical care are related to stages of activity limitations among older adults. Design: Cross-sectional study. Setting: Medicare Current Beneficiary Survey (MCBS) for calendar years 2001 to 2011. Participants: A population-based sample (N=42,584) of persons aged >= 65 years living in the community. Interventions: Not applicable. Main Outcome Measures: MCBS questions were categorized under 5 patient satisfaction and perceived quality dimensions: care coordination and quality, access barriers, technical skills of primary care physicians, interpersonal skills of primary care physicians, and quality of information provided by primary care physicians. Persons were classified into a stage of activity limitation (0-IV) derived from self-reported difficulty levels performing activities of daily living (ADL) and instrumental ADL. Results: Compared with older beneficiaries with no limitations at ADL stage 0, the adjusted odds ratios (ORs) for stage I (mild) to stage III (severe) for satisfaction with care coordination and quality ranged from .85 (95% confidence interval [CI], .80-.92) to .79 (95% CI, .70-.89). Compared with ADL stage 0, satisfaction with access barriers ranged from OR=.81 (95% CI, .76.87) at stage I to a minimum of OR=.67 (95% CI, .59-.76) at stage Similarly, compared with older beneficiaries at ADL stage 0, perceived quality of the technical skills of their primary care physician ranged from OR=.87 (95% CI, .82-.94) at stage I to a minimum of OR=.81 (95% CI, .72-.91) at stage III. Conclusions: Medicare beneficiaries at higher stages of activity limitation, although not necessarily the highest stage of activity limitation, reported less satisfaction with medical care. (C) 2015 by the American Congress of Rehabilitation Medicine C1 [Bogner, Hillary R.; McClintock, Heather F. de Vries] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Bogner, Hillary R.; McClintock, Heather F. de Vries; Hennessy, Sean; Kurichi, Jibby E.; Xie, Dawei; Kwong, Pui L.] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hennessy, Sean] Univ Penn, Ctr Pharmacoepidemiol Res & Training, Philadelphia, PA 19104 USA. [Streim, Joel. E.] Univ Penn, Perelman Sch Med, Dept Psychiat, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. [Streim, Joel. E.] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Pezzin, Liliana E.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Stineman, Margaret G.] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. RP Bogner, HR (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Family Med & Community Hlth, Perelman Sch Med, 928 Blockley Hall, Philadelphia, PA 19104 USA. EM hillary.bogner@uphs.upenn.edu FU Patient-Centered Outcomes Research Institute Project Program award [AD-12-11-4567]; National Institutes of Health [R01AG040105, R01HD074756]; American Heart Association [13GRNT17000021]; National Institute of Mental Health [R21 MH094940, R34 MH085880] FX Supported through a Patient-Centered Outcomes Research Institute Project Program award (no. AD-12-11-4567), by the National Institutes of Health (grant nos. R01AG040105, R01HD074756), the American Heart Association (award no. 13GRNT17000021), and the National Institute of Mental Health (grant nos. R21 MH094940, R34 MH085880). NR 35 TC 3 Z9 3 U1 3 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2015 VL 96 IS 10 BP 1810 EP 1819 DI 10.1016/j.apmr.2015.06.005 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CT2GX UT WOS:000362621100009 PM 26119464 ER PT J AU Ballen, KK Verter, F Kurtzberg, J AF Ballen, K. K. Verter, F. Kurtzberg, J. TI Umbilical cord blood donation: public or private? SO BONE MARROW TRANSPLANTATION LA English DT Review ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HYPOXIC-ISCHEMIC ENCEPHALOPATHY; UNRELATED DONOR; ACUTE-LEUKEMIA; SINGLE-CENTER; OUTCOMES; CHILDREN; BANKING; ENGRAFTMENT AB Umbilical cord blood (UCB) is a graft source for patients with malignant or genetic diseases who can be cured by allogeneic hematopoietic cell transplantation (HCT), but who do not have an appropriately HLA-matched family or volunteer unrelated adult donor. Starting in the 1990s, unrelated UCB banks were established, accepting donations from term deliveries and storing UCB units for public use. An estimated 730 000 UCB units have been donated and stored to date and similar to 35 000 UCB transplants have been performed worldwide. Over the past 20 years, private and family banks have grown rapidly, storing similar to 4 million UCB units for a particular patient or family, usually charging an up-front and yearly storage fee; therefore, these banks are able to be financially sustainable without releasing UCB units. Private banks are not obligated to fulfill the same regulatory requirements of the public banks. The public banks have released similar to 30 times more UCB units for therapy. Some countries have transitioned to an integrated banking model, a hybrid of public and family banking. Today, pregnant women, their families, obstetrical providers and pediatricians are faced with multiple choices about the disposition of their newborn's cord blood. In this commentary, we review the progress of UCB banking technology; we also analyze the current data on pediatric and adult unrelated UCB, including the recent expansion of interest in transplantation for hemoglobinopathies, and discuss emerging studies on the use of autologous UCB for neurologic diseases and regenerative medicine. We will review worldwide approaches to UCB banking, ethical considerations, criteria for public and family banking, integrated banking ideas and future strategies for UCB banking. C1 [Ballen, K. K.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [Verter, F.] Parents Guide Cord Blood Fdn, Houston, TX USA. [Kurtzberg, J.] Duke Univ, Med Ctr, Durham, NC USA. [Kurtzberg, J.] Carolinas Cord Blood Bank, Durham, NC USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Zero Emerson,Suite 118, Boston, MA 02114 USA. EM kballen@partners.org NR 69 TC 2 Z9 2 U1 4 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 2015 VL 50 IS 10 BP 1271 EP 1278 DI 10.1038/bmt.2015.124 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CT0PA UT WOS:000362497400002 PM 26030051 ER PT J AU Jaff, MR White, CJ Hiatt, WR Fowkes, GR Dormandy, J Razavi, M Reekers, J Norgren, L AF Jaff, Michael R. White, Christopher J. Hiatt, William R. Fowkes, Gerry R. Dormandy, John Razavi, Mahmood Reekers, Jim Norgren, Lars TI An Update on Methods for Revascularization and Expansion of the TASC Lesion Classification to Include Below-the-Knee Arteries: A Supplement to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) The TASC Steering Committee SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE angioplasty; arteries; claudication; critical limb ischemia; occlusion; peripheral artery disease; revascularization; stenosis; stents; surgery ID CRITICAL LIMB ISCHEMIA; AORTOILIAC OCCLUSIVE DISEASE; SUPERFICIAL FEMORAL-ARTERY; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; RANDOMIZED CONTROLLED-TRIAL; NITINOL STENT IMPLANTATION; DRUG-ELUTING STENTS; BARE-METAL STENTS; EXTREMITY BYPASS-SURGERY; VEIN GRAFT FAILURE AB The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today. (C) 2015 Wiley Periodicals, Inc. C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [White, Christopher J.] Univ Queensland, Ochsner Clin, Ochsner Clin Fdn, New Orleans, LA USA. [Hiatt, William R.] Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA. [Hiatt, William R.] CPC Clin Res, Aurora, CO USA. [Fowkes, Gerry R.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Dormandy, John] St George Hosp, London, England. [Razavi, Mahmood] St Joseph Hosp, Orange, CA USA. [Reekers, Jim] Univ Hosp Amsterdam, Acad Med Ctr, Amsterdam, Netherlands. [Norgren, Lars] Univ Orebro, Fac Med & Hlth, Dept Surg, SE-70182 Orebro, Sweden. RP Norgren, L (reprint author), Orebro Univ Hosp, Dept Surg, Surg, SE-70185 Orebro, Sweden. EM lars.norgren@regionorebrolan.se FU Aastrom Bio-sciences; Abbott Vascular; AnGes MG Inc; Bayer Schering Pharma; Biomedix; Cook; ev3; Medtronic; Mitsubishi Tanabe; Otsuka Pharmaceutical Co; Sanofi-Aventis; Toray Industries FX The author(s) report receiving the following financial support for the research, authorship, and/or publication of this article: VIVA Physicians [a 501(c)(3) education and research multispecialty organization] provided an unrestricted grant to the TASC organization. The development of this TASC II Supplement was supported by unrestricted educational grants awarded to Discovery London from (in alphabetical order): Aastrom Bio-sciences, Abbott Vascular, AnGes MG Inc, Bayer Schering Pharma, Biomedix, Cook, ev3, Medtronic, Mitsubishi Tanabe, Otsuka Pharmaceutical Co, Sanofi-Aventis, and Toray Industries. The companies did not participate in the discussions or in the preparation, review, or approval of the document. NR 90 TC 9 Z9 9 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT PY 2015 VL 86 IS 4 BP 611 EP 625 DI 10.1002/ccd.26122 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT4PW UT WOS:000362790100006 PM 26256456 ER PT J AU Blankenship, JC Rosenfield, K Jennings, HS AF Blankenship, James C. Rosenfield, Kenneth Jennings, Henry S., II TI Privileging and Credentialing for Interventional Cardiology Procedures SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE credentials; privileges; certification; accreditation; OPPE; FPPE ID CLINICAL COMPETENCE STATEMENT; EXPERT CONSENSUS DOCUMENT; AORTIC-VALVE-REPLACEMENT; UPDATE; CERTIFICATION; PERFORMANCE; SIMULATION AB Local institutional-specific credentialing and privileging for procedures is an important process for ensuring the quality of care provided by interventional cardiologists. Recently revised standards for coronary intervention and the blossoming of structural heart disease programs have generated controversy over these processes. How standards are set for credentialing and privileging is poorly understood by most interventional cardiologists, including those responsible for credentialing and privileging. Requirements from The Joint Commission dictate how credentialing and privileging is performed at hospitals they accredit. Physicians must be recredentialed every 2 years at each hospital, with privileges renewed at that time. Hospitals must review quality of physicians even more frequently using Ongoing Professional Practice Evaluations. Hospitals must also evaluate the performance of physicians when they join a hospital staff or when they begin performing new procedures using Focused Professional Practice Evaluations. Cardiology department directors and catheterization laboratory directors are responsible for recredentialing and reprivileging members of their departments. Individual physicians are responsible for cooperating with these processes, and for periodic recertification with specialty boards and governmental agencies. We provide specific guidance to help physicians navigate these processes. (C) 2015 Wiley Periodicals, Inc. C1 [Blankenship, James C.] Geisinger Med Ctr, Dept Cardiol, Danville, PA 17822 USA. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Jennings, Henry S., II] Vanderbilt Univ, Sch Med, Vanderbilt Heart & Vasc Inst, Nashville, TN 37212 USA. RP Blankenship, JC (reprint author), Geisinger Med Ctr, Dept Cardiol 27 75, 100 N Acad Ave, Danville, PA 17822 USA. EM jblankenship@geisinger.edu NR 26 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT PY 2015 VL 86 IS 4 BP 655 EP 663 DI 10.1002/ccd.25793 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT4PW UT WOS:000362790100013 PM 25534235 ER PT J AU Weinberg, I Drachman, DE AF Weinberg, Ido Drachman, Douglas E. TI Filtering Through the Data on Retrievable Inferior Vena Cava Filters SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID ANTICOAGULATION C1 Massachusetts Gen Hosp, Fireman Vasc Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Vasc Med Sect, Boston, MA 02114 USA. RP Weinberg, I (reprint author), Massachusetts Gen Hosp, Div Cardiol, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM iweinberg@partners.org NR 2 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT PY 2015 VL 86 IS 4 BP 726 EP 727 DI 10.1002/ccd.26227 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT4PW UT WOS:000362790100023 PM 26386236 ER PT J AU Ishida, JH Marafino, BJ McCulloch, CE Dalrymple, LS Dudley, RA Grimes, BA Johanseng, KL AF Ishida, Julie H. Marafino, Ben J. McCulloch, Charles E. Dalrymple, Lorien S. Dudley, R. Adams Grimes, Barbara A. Johanseng, Kirsten L. TI Receipt of Intravenous Iron and Clinical Outcomes among Hemodialysis Patients Hospitalized for Infection SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PRACTICE GUIDELINES; DIALYSIS PATIENTS; THERAPY; MANAGEMENT; ANEMIA; BOLUS; RISK AB Background and objectives Anemia guidelines for CKD recommend withholding intravenous iron in the setting of active infection, although no data specifically support this recommendation. This study aimed to examine the association between intravenous iron and clinical outcomes among hemodialysis patients hospitalized for infection. Design, setting, participants, & measurements This was a retrospective observational cohort study using data from the US Renal Data System of 22,820 adult Medicare beneficiaries on in-center hemodialysis who had received intravenous iron in the 14 days preceding their first hospitalization for bacterial infection in 2010. In multivariable analyses, the association between receipt of intravenous iron at any point from the day of hospital admission to discharge and all-cause 30-day mortality, mortality in 2010, length of hospital stay, and readmission for infection or death within 30 days of discharge was evaluated. Results There were 2463 patients (10.8%) who received intravenous iron at any point from the day of admission to discharge. Receipt of intravenous iron was not associated with age, dialysis vintage, or comorbidities. There were 2618 deaths within 30 days of admission and 6921 deaths in 2010 (median follow-up 173 days; 25th and 75th percentiles, 78-271 days). The median length of stay was 7 days (25th and 75th percentiles, 5-12 days). Receipt of intravenous iron was not associated with higher 30-day mortality (odds ratio, 0.86; 95% confidence interval [95% CI], 0.74 to 1.00), higher mortality in 2010 (hazard ratio, 0.92; 95% CI, 0.85 to 1.00), longer mean length of stay (10.1 days [95% CI, 9.7 to 10.5] versus 10.5 days [95% CI, 10.3 to 10.7]; P=0.05), or readmission for infection or death within 30 days of discharge (odds ratio, 1.08; 95% CI, 0.96 to 1.22) compared with no. receipt of intravenous iron. Conclusions This analysis does not support withholding intravenous iron upon admission for bacterial infection in hemodialysis patients, although clinical trials are required to make definitive recommendations. C1 [Ishida, Julie H.; Johanseng, Kirsten L.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, Div Nephrol, San Francisco, CA 94143 USA. [Dudley, R. Adams] Univ Calif San Francisco, Dept Med, Philip R Lee Inst Hlth Policy Studies, Div Pulm & Crit Care, San Francisco, CA USA. [McCulloch, Charles E.; Dudley, R. Adams; Grimes, Barbara A.; Johanseng, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Marafino, Ben J.; Dudley, R. Adams] Univ Calif San Francisco, Ctr Healthcare Value, San Francisco, CA 94143 USA. [Ishida, Julie H.; Johanseng, Kirsten L.] San Francisco VA Med Ctr, Div Nephrol, Dept Med, San Francisco, CA 94121 USA. [Dalrymple, Lorien S.] Univ Calif Davis, Dept Med, Div Nephrol, Davis, CA 95616 USA. RP Ishida, JH (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 4150 Clement St,111J, San Francisco, CA 94121 USA. EM julie.ishida@ucsf.edu FU American Society of Nephrology; National Institute of Diabetes and Digestive and Kidney Diseases [K24-DK085153, K23-DK093584, N01-DK7005]; University of California, San Francisco Clinical and Translational Science Institute [UL1-TR000004] FX This publication was made possible by grants from the American Society of Nephrology (to J.H.I.), the National Institute of Diabetes and Digestive and Kidney Diseases (K24-DK085153 to K.L.J., K23-DK093584 to L.S.D., and N01-DK7005 to K.L.J. and B.A.G.), and the University of California, San Francisco Clinical and Translational Science Institute (UL1-TR000004 to C.E.M. and B.A.G.). NR 22 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD OCT PY 2015 VL 10 IS 10 BP 1799 EP 1805 DI 10.2215/CJN.01090115 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CT2JK UT WOS:000362627600015 PM 26416943 ER PT J AU Elder, WB Morrow, SL Brooks, GR AF Elder, William B. Morrow, Susan L. Brooks, Gary R. TI Sexual Self-Schemas of Gay Men: A Qualitative Investigation SO COUNSELING PSYCHOLOGIST LA English DT Article DE gender; LGBT; multiculturalism; qualitative; race; ethnicity ID GENDER-ROLE CONFLICT; HETEROSEXUAL MEN; RELATIONSHIP SATISFACTION; PSYCHOLOGICAL DISTRESS; COUNSELING PSYCHOLOGY; RACIAL IDENTITY; MASCULINE SELF; BISEXUAL MEN; BODY-IMAGE; PORNOGRAPHY AB Self-schemas derive from past experience, influence current experiences, and facilitate the processing of sexual information. Using this concept, this study addressed the following question: How do gay men understand their own sexual self-schemas? Perspectives of 20 gay men were drawn together using a grounded theory methodology and member checking. A seven-category model emerged depicting the behaviors and values participants described as the gay male sexual schema (e.g., Avoidance of Emotional Expression; Pornography and Sexual Orientation Identity; Physically Attractive Men; Managing Sex and Social Perception; Competition for Men; Sex, Emotion, and Intimacy; and Commitment and Work in Relationships). In addition, all participants discussed a process of sexual self-schema transition over time. The resulting model may be used in counseling and in social justice and advocacy to produce adaptive changes for gay male clients. C1 [Elder, William B.] South Texas Vet Hlth Care Syst, San Antonio, TX 78240 USA. [Morrow, Susan L.] Univ Utah, Counseling Psychol Program, Salt Lake City, UT USA. [Brooks, Gary R.] Baylor Univ, Doctoral Psychol Program, Waco, TX 76798 USA. RP Elder, WB (reprint author), South Texas Vet Hlth Care Syst, 5788 Eckhert Rd, San Antonio, TX 78240 USA. EM William.Elder2@va.gov NR 101 TC 0 Z9 0 U1 5 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0011-0000 EI 1552-3861 J9 COUNS PSYCHOL JI Couns. Psychol. PD OCT PY 2015 VL 43 IS 7 BP 942 EP 969 DI 10.1177/0011000015606222 PG 28 WC Psychology, Applied SC Psychology GA CT0JS UT WOS:000362481900001 ER PT J AU Elder, WB Morrow, SL Brooks, GR AF Elder, William B. Morrow, Susan L. Brooks, Gary R. TI Sexual Self-Schemas of Bisexual Men: A Qualitative Investigation SO COUNSELING PSYCHOLOGIST LA English DT Article DE multiculturalism; gender; LGBT; race; ethnicity; qualitative ID AFRICAN-AMERICAN MEN; PERSONAL CONSTRUCT THEORY; GENDER-ROLE-CONFLICT; GAY MEN; COUNSELING PSYCHOLOGY; IDENTITY DEVELOPMENT; HOMOSEXUAL IDENTITY; BODY-IMAGE; AROUSAL PATTERNS; MALE-ADOLESCENTS AB This qualitative study investigated the sexual self-schemas and masculinity ideologies of 20 bisexual men. Sexual self-schema was defined as a cognitive generalization about sexual aspects of the self, as derived from past experience and sociocultural context, which guides current experiences and facilitates the processing of sexual information. In-depth interviews, a focus group, documentary evidence, and grounded theory analysis were used. Categories were coded and analyzed, revealing two models. The first, the sexual self-schema of bisexual men, is an eight-category model of the bisexual male sexual self-schema describing men's relationships with other men and with women, as well as attitudes about themselves. The second model, the process of emerging awareness of bisexual attraction, outlines how sexual and romantic relationship experiences lead to bisexual sexual orientation identity. The two theoretical models depict how bisexual men understand their own sexual self-schemas. Implications for counseling psychology research and practice are addressed. C1 [Elder, William B.] South Texas Vet Hlth Care Syst, San Antonio, TX 78240 USA. [Morrow, Susan L.] Univ Utah, Counseling Psychol Program, Salt Lake City, UT USA. [Brooks, Gary R.] Baylor Univ, Doctoral Psychol Program, Waco, TX 76798 USA. RP Elder, WB (reprint author), South Texas Vet Hlth Care Syst, Psychol Serv, 5788 Eckhert Rd,116A PCT, San Antonio, TX 78240 USA. EM William.Elder2@va.gov NR 150 TC 0 Z9 0 U1 7 U2 20 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0011-0000 EI 1552-3861 J9 COUNS PSYCHOL JI Couns. Psychol. PD OCT PY 2015 VL 43 IS 7 BP 970 EP 1007 DI 10.1177/0011000015608242 PG 38 WC Psychology, Applied SC Psychology GA CT0JS UT WOS:000362481900002 ER PT J AU Walmer, R Huynh, J Wenger, J Ankers, E Mantha, AB Ecker, J Thadhani, R Park, E Bentley-Lewis, R AF Walmer, Rebecca Huynh, Jennifer Wenger, Julia Ankers, Elizabeth Mantha, Allison Bryant Ecker, Jeffrey Thadhani, Ravi Park, Elyse Bentley-Lewis, Rhonda TI MENTAL HEALTH DISORDERS SUBSEQUENT TO GESTATIONAL DIABETES MELLITUS DIFFER BY RACE/ETHNICITY SO DEPRESSION AND ANXIETY LA English DT Article DE anxiety; anxiety disorders; depression; ethnicity; race; pregnancy and postpartum; epidemiology ID POSTPARTUM DEPRESSION; ETHNIC-DIFFERENCES; UNITED-STATES; RISK-FACTORS; WOMEN; PREGNANCY; DIAGNOSIS; STRESS; PERIOD; CARE AB IntroductionThe relationship between gestational diabetes mellitus (GDM) and postpregnancy mental health disorders has been inconsistently reported. Additionally, race/ethnicity data are limited. We sought to elucidate the intersection of these relationships. MethodsWe analyzed 18,109 women aged 18-40 with self-reported race/ethnicity. Women with (n = 659) and without (n = 14,461) GDM were followed for a median of 4.4 (interquartile range 1.4-6.8) and 4.0 (1.5-6.4) years, respectively, for incident mental health disorders. Multivariable repeated measures analyses were conducted to examine associations between GDM and postpregnancy mental health disorders, race/ethnicity, and the interaction of these factors. ResultsWomen with compared to women without GDM were older (mean standard deviation, 32 +/- 5 vs. 30 +/- 5 years; P < .001) and had higher body mass index (29.0 +/- 7.2 vs. 25.3 +/- 5.2 kg/m(2); P < .001). GDM was associated with increased risk for depression and anxiety after adjusting for age and pregnancy complications; however, loss of significance in the fully adjusted model for depression (odds ratio [95% CI]: 1.29 [0.98, 1.70]; P = .064) and anxiety (1.14 [0.83, 1.57], P = .421) suggested that clinical and socioeconomic factors influence this relationship. Hispanic compared to white women had a greater risk for depression (1.40 [1.15, 1.72]; P = .001), even after multivariable adjustment. The interaction between GDM and race was evident in complication-adjusted but not fully adjusted models. ConclusionsThe incidence of mental health disorders subsequent to GDM was attenuated after adjustment for clinical and socioeconomic factors. Moreover, race/ethnicity influenced this relationship. Further investigation is warranted to clarify potential underlying mechanisms. (C) 2015 Wiley Periodicals, Inc. C1 [Walmer, Rebecca; Huynh, Jennifer; Bentley-Lewis, Rhonda] Massachusetts Gen Hosp, Med Diabet Unit, Boston, MA 02114 USA. [Wenger, Julia; Ankers, Elizabeth; Thadhani, Ravi] Massachusetts Gen Hosp, Med Div Nephrol, Boston, MA 02114 USA. [Mantha, Allison Bryant; Ecker, Jeffrey] Massachusetts Gen Hosp, Obstet & Gynecol, Boston, MA 02114 USA. [Park, Elyse] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. RP Bentley-Lewis, R (reprint author), Massachusetts Gen Hosp, Med Diabet Unit, 55 Fruit St,Bulfinch 4-415, Boston, MA 02114 USA. EM rbentleylewis@mgh.harvard.edu FU RobertWood Johnson Foundation Harold Amos Medical Faculty Development Program; Massachusetts General Hospital Executive Committee on Research/Multicultural Affairs Office Physician-Scientist Development Award [NIH R03DK096152]; [NIH K24DK094872] FX Contract grant sponsors: RobertWood Johnson Foundation Harold Amos Medical Faculty Development Program; Massachusetts General Hospital Executive Committee on Research/Multicultural Affairs Office Physician-Scientist Development Award; Contract grant number: NIH R03DK096152 (to R.B.-L.); Contract grant number: NIH K24DK094872 (to R.T.). NR 43 TC 2 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2015 VL 32 IS 10 BP 774 EP 782 DI 10.1002/da.22388 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CS8WA UT WOS:000362369200008 PM 26130074 ER PT J AU Kita, T Clermont, AC Murugesan, N Zhou, QF Fujisawa, K Ishibashi, T Aiello, LP Feener, EP AF Kita, Takeshi Clermont, Allen C. Murugesan, Nivetha Zhou, Qunfang Fujisawa, Kimihiko Ishibashi, Tatsuro Aiello, Lloyd Paul Feener, Edward P. TI Plasma Kallikrein-Kinin System as a VEGF-Independent Mediator of Diabetic Macular Edema SO DIABETES LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-RETINAL BARRIER; NITRIC-OXIDE SYNTHASE; VASCULAR DYSFUNCTION; VITREOUS LEVELS; VISUAL-ACUITY; RETINOPATHY; BREAKDOWN; PROTEOME; DISEASE AB This study characterizes the kallikrein-kinin system in vitreous from individuals with diabetic macular edema (DME) and examines mechanisms contributing to retinal thickening and retinal vascular permeability (RVP). Plasma prekallikrein (PPK) and plasma kallikrein (PKal) were increased twofold and 11.0-fold (both P < 0.0001), respectively, in vitreous from subjects with DME compared with those with a macular hole (MH). While the vascular endothelial growth factor (VEGF) level was also increased in DME vitreous, PKal and VEGF concentrations do not correlate (r= 0.266, P = 0.112). Using mass spectrometry-based proteomics, we identified 167 vitreous proteins, including 30 that were increased in DME (fourfold or more, P < 0.001 vs. MH). The majority of proteins associated with DME displayed a higher correlation with PPK than with VEGF concentrations. DME vitreous containing relatively high levels of PKal and low VEGF induced RVP when injected into the vitreous of diabetic rats, a response blocked by bradykinin receptor antagonism but not by bevacizumab. Bradykinin-induced retinal thickening in mice was not affected by blockade of VEGF receptor 2. Diabetes-induced RVP was decreased by up to 78% (P < 0.001) in Klkb1 (PPK)-deficient mice compared with wild-type controls. B2- and B1 receptor-induced RVP in diabetic mice was blocked by endothelial nitric oxide synthase (NOS) and inducible NOS deficiency, respectively. These findings implicate the PKal pathway as a VEGF-independent mediator of DME. C1 [Kita, Takeshi; Clermont, Allen C.; Murugesan, Nivetha; Zhou, Qunfang; Aiello, Lloyd Paul; Feener, Edward P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Fujisawa, Kimihiko; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 812, Japan. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Beetham Eye Inst, Boston, MA 02115 USA. [Feener, Edward P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM edward.feener@joslin.harvard.edu FU NEI NIH HHS [EY-019029, R01 EY019029, T32 EY007145, T32-EY-007145]; NIDDK NIH HHS [DK-36836, P30 DK036836] NR 49 TC 9 Z9 10 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD OCT PY 2015 VL 64 IS 10 BP 3588 EP 3599 DI 10.2337/db15-0317 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CT2IG UT WOS:000362624600028 PM 25979073 ER PT J AU Back, SE Gros, DF Price, M LaRowe, S Flanagan, J Brady, KT Davis, C Jaconis, M McCauley, JL AF Back, Sudie E. Gros, Daniel F. Price, Matthew LaRowe, Steve Flanagan, Julianne Brady, Kathleen T. Davis, Charles Jaconis, Maryanne McCauley, Jenna L. TI Laboratory-induced stress and craving among individuals with prescription opioid dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Stress; Trier; Cues; Prescription opioids; Opiates ID ALCOHOL CUE REACTIVITY; DRUG-ABUSE; PSYCHOSOCIAL STRESS; CONTROLLED-TRIAL; COLD PRESSOR; CHRONIC PAIN; RELAPSE; ADDICTION; SEEKING; MECHANISMS AB Background: Stress and conditioned drug cues have been implicated in the initiation, maintenance and relapse to substances of abuse. Although stress and drug cues are often encountered together, little research exists on whether stress potentiates the response to drug cues. Method: Participants (N = 75) were 39 community recruited individuals with current prescription opioid (PO) dependence and 36 healthy controls. Participants stayed overnight in the hospital for one night and then completed laboratory testing the following morning. During laboratory testing, participants were randomly assigned to a stress task (Trier Social Stress Task; TSST) or a no-stress condition. Following the stress manipulation, all participants completed a PO cue paradigm. Immediately before and after the stress and cue tasks, the following were assessed: subjective (stress, craving, anger, sadness, happiness), physiological (heart rate, blood pressure, galvanic skin response), and neuroendocrine responses (cortisol and dehydroepiandrosterone). Results: Internal validity of the stress task was demonstrated, as evidenced by significantly higher subjective stress, as well as cortisol, heart rate and blood pressure in the TSST compared to the no-stress group. Individuals with PO dependence evidenced significantly greater reactivity to the stress task than controls. Craving increased significantly in response to the drug cue task among PO participants. No stress x cue interaction was observed. Conclusions: In this study, heightened stress reactivity was observed among individuals with PO dependence. Exposure to acute stress, however, did not potentiate craving in response to conditioned drug cues. Published by Elsevier Ireland Ltd. C1 [Back, Sudie E.; Gros, Daniel F.; LaRowe, Steve; Flanagan, Julianne; Brady, Kathleen T.; Davis, Charles; Jaconis, Maryanne; McCauley, Jenna L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Back, Sudie E.; Gros, Daniel F.; LaRowe, Steve; Brady, Kathleen T.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Price, Matthew] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. RP Back, SE (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, 67 President St,POB 250861, Charleston, SC 29425 USA. EM backs@musc.edu FU National Institute on Drug Abuse (NIDA) [K23 DA021228, DA036566, K24 DA00435]; Department of Veteran Affairs Clinical Sciences Research and Development [CX000845]; NIAAA [AA007474] FX This work was supported by grants from the National Institute on Drug Abuse (NIDA) to S. E. Back (K23 DA021228), J.L. McCauley (DA036566) and K. T. Brady (K24 DA00435), and a grant from the Department of Veteran Affairs Clinical Sciences Research and Development to D. F. Gros (CX000845). The authors would also like to acknowledge support from NIAAA T32 grant number AA007474 (Woodward, J.). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of NIDA, the Department of Veterans Affairs, or the United States government. We would like to thank the following individuals for their assistance with study design and data collection: Dr. Ronald See, Dr. Elizabeth Cox, Ms. Mary Ashley Mercer, Ms. Katie Lawson, and Ms. Emily Hartwell. NR 70 TC 1 Z9 1 U1 6 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2015 VL 155 BP 60 EP 67 DI 10.1016/j.drugalcdep.2015.08.019 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CS8AB UT WOS:000362307000009 PM 26342626 ER PT J AU Brooks, CR Yeung, MY Brooks, YS Chen, H Ichimura, T Henderson, JM Bonventre, JV AF Brooks, Craig R. Yeung, Melissa Y. Brooks, Yang S. Chen, Hui Ichimura, Takaharu Henderson, Joel M. Bonventre, Joseph V. TI KIM-1-/TIM-1-mediated phagocytosis links ATG5-/ULK1-dependent clearance of apoptotic cells to antigen presentation SO EMBO JOURNAL LA English DT Article DE acute kidney injury; T regs; biomarker; heterophagy; MHC ID KIDNEY INJURY MOLECULE-1; CROSS-PRESENTATION; RHEUMATOID-ARTHRITIS; MULTILAMELLAR BODIES; AUTOPHAGIC VACUOLES; KOREAN POPULATION; EPITHELIAL-CELLS; MATURATION STEP; NADPH OXIDASES; TIM-1 GENE AB Phagocytosis of apoptotic cells by both professional and semi-professional phagocytes is required for resolution of organ damage and maintenance of immune tolerance. KIM-1/TIM-1 is a phosphatidylserine receptor that is expressed on epithelial cells and can transform the cells into phagocytes. Here, we demonstrate that KIM-1 phosphorylation and association with p85 results in encapsulation of phagosomes by lipidated LC3 in multi-membrane organelles. KIM-1-mediated phagocytosis is not associated with increased ROS production, and NOX inhibition does not block LC3 lipidation. Autophagy gene expression is required for efficient clearance of apoptotic cells and phagosome maturation. KIM-1-mediated phagocytosis leads to pro-tolerogenic antigen presentation, which suppresses CD4 T-cell proliferation and increases the percentage of regulatory T cells in an autophagy gene-dependent manner. Taken together, these data reveal a novel mechanism of epithelial biology linking phagocytosis, autophagy and antigen presentation to regulation of the inflammatory response. C1 [Brooks, Craig R.; Yeung, Melissa Y.; Ichimura, Takaharu; Bonventre, Joseph V.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02115 USA. [Yeung, Melissa Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr, Boston, MA 02115 USA. [Brooks, Yang S.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Brooks, Yang S.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Chen, Hui; Henderson, Joel M.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Bonventre, Joseph V.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Brooks, CR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02115 USA. EM crbrooks@partners.org; joseph_bonventre@hms.harvard.edu FU US National Institutes of Health (NIH) [DK39773, DK72381, DK088418, DK099473] FX We would like to thank Dr. Vijay Kuchroo for the gift of the KIM-1Delta mucin mice. We thank Dr. Lewis C. Cantley for the p85 alpha/beta wild-type and knockout MEFs. We thank Dr. Tamotsu Yoshimori for the pmRFP-LC3 and ptfLC3 constructs; Dr. angstrom sa B. Gustafsson for the pmCherry-ATG5-K130R construct; and Dr. Noboru Mizushima for the pMXs-IP-EGFP-ULK1 (K46N) and GFP-LC3 constructs. This work was supported by US National Institutes of Health (NIH) grants DK39773 and DK72381 to J.V.B. and DK088418 and DK099473 to C.R.B. NR 73 TC 15 Z9 15 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD OCT 1 PY 2015 VL 34 IS 19 BP 2441 EP 2464 DI 10.15252/embj.201489838 PG 24 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CT0BD UT WOS:000362457800009 PM 26282792 ER PT J AU Zhang, HB Guan, MP Townsend, KL Huang, TL An, D Yan, X Xue, RD Schulz, TJ Winnay, J Mori, M Hirshman, MF Kristiansen, K Tsang, JS White, AP Cypess, AM Goodyear, LJ Tseng, YH AF Zhang, Hongbin Guan, Meiping Townsend, Kristy L. Huang, Tian Lian An, Ding Yan, Xu Xue, Ruidan Schulz, Tim J. Winnay, Jonathon Mori, Marcelo Hirshman, Michael F. Kristiansen, Karsten Tsang, John S. White, Andrew P. Cypess, Aaron M. Goodyear, Laurie J. Tseng, Yu-Hua TI MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1 signaling network SO EMBO REPORTS LA English DT Article DE brown adipogenesis; differentiation; metabolism; microRNA; UCP1 ID ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; ADIPOSE-TISSUE; SKELETAL-MUSCLE; GENE-EXPRESSION; C/EBP-BETA; WHITE FAT; MITOCHONDRIAL BIOGENESIS; ADIPOCYTE PROGENITORS; ENERGY-EXPENDITURE AB Brown adipose tissue (BAT) dissipates chemical energy as heat and can counteract obesity. MicroRNAs are emerging as key regulators in development and disease. Combining microRNA and mRNA microarray profiling followed by bioinformatic analyses, we identified miR-455 as a new regulator of brown adipogenesis. miR-455 exhibits a BAT-specific expression pattern and is induced by cold and the browning inducer BMP7. In vitro gain- and loss-of-function studies show that miR-455 regulates brown adipocyte differentiation and thermogenesis. Adipose-specific miR-455 transgenic mice display marked browning of subcutaneous white fat upon cold exposure. miR-455 activates AMPK1 by targeting HIF1an, and AMPK promotes the brown adipogenic program and mitochondrial biogenesis. Concomitantly, miR-455 also targets the adipogenic suppressors Runx1t1 and Necdin, initiating adipogenic differentiation. Taken together, the data reveal a novel microRNA-regulated signaling network that controls brown adipogenesis and may be a potential therapeutic target for human metabolic disorders. C1 [Zhang, Hongbin; Guan, Meiping; Townsend, Kristy L.; Huang, Tian Lian; An, Ding; Yan, Xu; Xue, Ruidan; Schulz, Tim J.; Winnay, Jonathon; Mori, Marcelo; Hirshman, Michael F.; Cypess, Aaron M.; Goodyear, Laurie J.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Zhang, Hongbin] Univ Copenhagen, Dept Biomed Sci, Copenhagen, Denmark. [Guan, Meiping] Southern Med Univ, Nanfang Hosp, Dept Endocrinol & Metab, Guangzhou, Guangdong, Peoples R China. [Schulz, Tim J.] German Inst Human Nutr, Adipocyte Dev Res Grp, Potsdam, Germany. [Mori, Marcelo] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo, Brazil. [Kristiansen, Karsten] Univ Copenhagen, Dept Biol, Copenhagen, Denmark. [Tsang, John S.] NIAID, Syst Genom & Bioinformat Unit, Lab Syst Biol, Bethesda, MD 20892 USA. [Tsang, John S.] NIH, Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA. [White, Andrew P.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Boston, MA 02115 USA. [Tseng, Yu-Hua] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Zhang, HB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. EM hongbin@sund.ku.dk; yu-hua.tseng@joslin.harvard.edu RI Kristiansen, Karsten/J-5148-2014; Schulz, Tim/F-4842-2013 OI Kristiansen, Karsten/0000-0002-6024-0917; Schulz, Tim/0000-0002-8413-3972 FU NIH [R01 DK077097, R01AR042238, T32 DK007260-33, NIH F32 DK091996]; Joslin Diabetes Center's Diabetes Research Center (DRC from the NIDDK) [P30 DK036836]; American Diabetes Association [ADA 7-12-BS-191]; Novo Nordisk Foundation; Lundbeck Foundation; Augustinus Foundation; American Diabetes Association Mentor-Based Award [7-12-MN]; Intramural Program of the NIAID/NIH FX We thank Dr. Yong-Xu Wang for providing the brown preadipocyte cell line, Exiqon A/S for providing microRNA mimics, and Dr. Marc Uldry and Dr. Bruce Spiegelman for providing the PGC1 alpha KO brown preadipocyte cell line. We thank Elizabeth Caniano for administrative assistance to the manuscript. We also thank Dr. Nils Billestrup and Dr. Jens Hoiriis Nielsen for help with experimental materials. This work was supported in part by NIH grants R01 DK077097 (Y.-H.T.), and Joslin Diabetes Center's Diabetes Research Center (DRC; P30 DK036836 from the NIDDK), a research grant from the American Diabetes Association (ADA 7-12-BS-191 to Y.-H.T.), research grants from the Novo Nordisk Foundation, Lundbeck Foundation and Augustinus Foundation (to H.Z.), NIH grant R01AR042238, and American Diabetes Association Mentor-Based Award 7-12-MN (to L.J.G.) and partially supported by the Intramural Program of the NIAID/NIH (to J.S.T.). K.L.T was funded by NIH T32 DK007260-33 and NIH F32 DK091996. NR 59 TC 12 Z9 13 U1 5 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-221X EI 1469-3178 J9 EMBO REP JI EMBO Rep. PD OCT PY 2015 VL 16 IS 10 BP 1378 EP 1393 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CT1KV UT WOS:000362558100016 PM 26303948 ER PT J AU Deck, GM Nadkarni, N Montouris, GD Lovett, A AF Deck, Gina M. Nadkarni, Neil Montouris, Georgia D. Lovett, Alexandra TI Congenital malformations in infants exposed to antiepileptic medications in utero at Boston Medical Center from 2003 to 2010 SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy; Congenital malformation; Teratogenicity; Pregnancy; Antiepileptic medication; Benzodiazepine ID BIRTH-DEFECTS; PREGNANCY; EPILEPSY; DRUGS; WOMEN; PREVALENCE; MANAGEMENT; ATLANTA; UPDATE; RISK AB Objective: The aim of this study was to determine the frequency of association of major congenital malformations in pregnancy in women exposed to antiepileptic drugs (AEDs) in an inner city population. Background: Approximately 0.3-0.5% of all pregnancies involve women with epilepsy. The risk of congenital malformations associated with AED therapy has been well documented, ranging from 2 to 10% as compared to a rate of 3% in the general population. However, the risk of these occurring in a higher risk population, such as an inner city tertiary care center, with multiple comorbidities is not as well known. Design/methods: Using the Boston Medical Center Database between the years 2003 and 2010, a list of all infants born with major congenital malformations (MCMs) to mothers on AEDs was compiled. Major congenital malformations were defined as cleft lip and/or palate, ventricular or atrial septal defect, other cardiac malformations, and urogenital defects. During pregnancy, AED exposure including serum levels, other medication exposures, breakthrough seizure frequency, positive toxicology tests, and other maternal comorbidities were also analyzed. Results: Of 17,246 live births between 2003 and 2010, 330 of those births demonstrated a MCM (malformation rate of 1.91%). Of those births, 64 mothers had epilepsy and were exposed to AED therapy during pregnancy, accounting for 0.37% of all births during this time period. Overall, three pregnancies in women with epilepsy resulted in a baby with a MCM, accounting for a 4.7% malformation rate in this patient population. In mothers on AEDs for other indications, the MCM rate was slightly higher, 5.0%, and in women on benzodiazepine monotherapy during pregnancy, the rate was quite high, 10.6%. (C) 2015 Elsevier Inc. All rights reserved. C1 [Deck, Gina M.; Nadkarni, Neil; Montouris, Georgia D.; Lovett, Alexandra] Boston Univ, Sch Med, Dept Neurol, Boston Med Ctr, Boston, MA 02118 USA. RP Deck, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 55 Fruit St,WACC 720, Boston, MA 02114 USA. EM gdeck@mgh.harvard.edu; nnadkarni87@gmail.com; Georgia.montouris@bmc.org; ajlovett@partners.org NR 18 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD OCT PY 2015 VL 51 BP 166 EP 169 DI 10.1016/j.yebeh.2015.07.001 PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA CS7TW UT WOS:000362290200026 PM 26283306 ER PT J AU Mela, T Singh, JP AF Mela, Theofanie Singh, Jagmeet P. TI Leadless pacemakers: leading us into the future? SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID COMPLICATIONS; TRIAL AB This editorial refers to 'Early performance of a miniaturized leadless cardiac pacemaker: the Micra Transcatheter Pacing Study'(dagger), by P. Ritter et al., on page 2510. C1 [Mela, Theofanie; Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Cardiol Div,Heart Ctr, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Heart Ctr, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@mgh.harvard.edu NR 8 TC 1 Z9 1 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD OCT 1 PY 2015 VL 36 IS 37 BP 2520 EP 2522 DI 10.1093/eurheartj/ehv261 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT5CG UT WOS:000362824500012 PM 26282468 ER PT J AU Blobel, GA Bodine, D Brand, M Crispino, J de Bruijn, MFTR Nathan, D Papayannopoulou, T Porcher, C Strouboulis, J Zon, L Higgs, DR Stamatoyannopoulos, G Engel, JD AF Blobel, Gerd A. Bodine, David Brand, Marjorie Crispino, John de Bruijn, Marella F. T. R. Nathan, David Papayannopoulou, Thalia Porcher, Catherine Strouboulis, John Zon, Len Higgs, Douglas R. Stamatoyannopoulos, George Engel, James Douglas TI An international effort to cure a global health problem: A report on the 19th Hemoglobin Switching Conference SO EXPERIMENTAL HEMATOLOGY LA English DT Review ID CAUSES HEREDITARY PERSISTENCE; FETAL-HEMOGLOBIN; GENE-EXPRESSION; BETA-THALASSEMIA; ERYTHROID-CELLS; GAMMA-GLOBIN; TRANSCRIPTION FACTORS; CHROMATIN OCCUPANCY; BCL11A; ERYTHROPOIESIS AB Every 2 years since 1978, an international group of scientists, physicians, and other researchers meet to discuss the latest developments in the underlying etiology, mechanisms of action, and developmental acquisition of cellular and systemic defects exhibited and elicited by the most common inherited human disorders, the hemoglobinopathies. The 19th Hemoglobin Switching Conference, held in September 2014 at St. John's College in Oxford, once again exceeded all expectations by describing cutting edge research in cellular, molecular, developmental, and genomic advances focused on these diseases. The conference comprised about 60 short talks over 3 days by leading investigators in the field. This meeting report describes the highlights of the conference. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. C1 [Blobel, Gerd A.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Div Hematol, Philadelphia, PA 19104 USA. [Bodine, David] NHGRI, NIH, Bethesda, MD 20892 USA. [Brand, Marjorie] Ottawa Hosp Res Inst, Sprott Ctr Stem Cell Res, Ottawa, ON, Canada. [Crispino, John] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL 60611 USA. [de Bruijn, Marella F. T. R.; Porcher, Catherine; Higgs, Douglas R.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford OX3 9DU, England. [de Bruijn, Marella F. T. R.; Porcher, Catherine; Higgs, Douglas R.] Oxford Univ Hosp, NIHR Oxford Biomed Ctr, BRC Blood Theme, Oxford, England. [Nathan, David] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Pediat,Dept Pediat Onc, Div Hematol & Oncol,Boston Childrens Hosp, Boston, MA 02115 USA. [Nathan, David] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol,Dept Med, Div Hematol & Oncol,Boston Childrens Hosp, Boston, MA 02115 USA. [Papayannopoulou, Thalia; Stamatoyannopoulos, George] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Strouboulis, John] Biomed Sci Res Ctr Alexander Fleming, Div Mol Oncol, Vari, Greece. [Zon, Len] Boston Childrens Hosp, HHMI, Boston, MA USA. [Engel, James Douglas] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI USA. RP Engel, JD (reprint author), Univ Michigan, Sch Med, Dept Cell & Dev Biol, Biomed Sci Res 3035, 109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM engel@umich.edu RI Porcher, Catherine/D-7026-2016; OI Crispino, John/0000-0002-8182-8306 FU Medical Research Council [MC_U137961144, G1000801, MC_U137961145, MC_UU_12009/2, MC_UU_12009/9]; NHLBI NIH HHS [U01 HL117658] NR 74 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 2015 VL 43 IS 10 BP 821 EP 837 DI 10.1016/j.exphem.2015.06.008 PG 17 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CT3GF UT WOS:000362694500001 PM 26143582 ER PT J AU Inra, JA Steyerberg, EW Grover, S McFarland, A Syngal, S Kastrinos, F AF Inra, Jennifer A. Steyerberg, Ewout W. Grover, Shilpa McFarland, Ashley Syngal, Sapna Kastrinos, Fay TI Racial variation in frequency and phenotypes of APC and MUTYH mutations in 6,169 individuals undergoing genetic testing SO GENETICS IN MEDICINE LA English DT Article DE familial adenomatous polyposis; genetic testing; MUTYH-associated polyposis; phenotype; race ID FAMILIAL ADENOMATOUS POLYPOSIS; COLORECTAL-CANCER; GERMLINE MUTATIONS; LYNCH SYNDROME; MYH; PREVALENCE; PREMM1,2,6; HISTORY; RISK; FAP AB Purpose: The aim of this study was to assess whether differences in frequency and phenotype of APC and MUTYH mutations exist among racially/ethnically diverse populations. Methods: We studied 6,169 individuals with a personal and/or family history of colorectal cancer (CRC) and polyps. APC testing involved full sequencing/large rearrangement analysis (FS/LRA); MUTYH involved "panel testing" (for Y165C, G382D mutations) or FS/LRA performed by Myriad Genetics, a commercial laboratory. Subjects were identified as Caucasian, Asian, African American (AA), or other. Statistical tests included chi(2), Fisher's exact test, analysis of variance, and z approximation. Results: Among participants, 17.5% had pathogenic APC mutations and 4.8% were biallelic MUTYH carriers. With regard to race/ethnicity, 18% were non-Caucasian, with > 100 adenomas and younger ages at adenoma or CRC diagnosis (P < 0.0001) than Caucasians. The overall APC mutation rate was higher in Asians, AAs, and others compared with Caucasians (25.2, 30.9, 24, and 15.5%, respectively; P < 0.0001) but was similar in all groups when adjusted for polyp burden. More MUTYH biallelic carriers were Caucasian or other than Asian or AA (5, 7, 2.7, and 0.3%, respectively; P < 0.0001). Among Caucasians, 5% were biallelic carriers identified by panel testing versus 2% identified by sequencing/large rearrangement analysis (LRA) (P = 0.002). Among non-Caucasians, 3% undergoing panel testing were biallelic carriers versus 10% identified by sequencing/LRA (P < 0.0002). Conclusion: Non-Caucasians undergo genetic testing at more advanced stages of polyposis and/or are younger at CRC/polyp diagnosis. Restricted MUTYH analysis may miss significant numbers of biallelic carriers, particularly in non-Caucasians. C1 [Inra, Jennifer A.; Grover, Shilpa; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Inra, Jennifer A.; Grover, Shilpa; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Steyerberg, Ewout W.] Erasmus MC, Ctr Med Decis Making, Rotterdam, Netherlands. [McFarland, Ashley; Kastrinos, Fay] Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY 10027 USA. [Syngal, Sapna] Dana Farber Canc Inst, Populat Sci Div, Boston, MA 02115 USA. [Kastrinos, Fay] Herbert Irving Comprehens Canc Ctr, New York, NY USA. RP Kastrinos, F (reprint author), Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY 10027 USA. EM fk18@columbia.edu OI Syngal, Sapna/0000-0001-5487-7471 FU National Institutes of Health/National Cancer Institute [K07 CA151769, K24113433] FX The authors thank Lynn Ann Burbidge and Richard J. Wenstrup of Myriad Genetics Laboratories for their assistance in data retrieval and preparation. This study was supported by National Institutes of Health/National Cancer Institute grants K07 CA151769 (F.K.) and K24113433 (S.S.). NR 28 TC 2 Z9 2 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD OCT PY 2015 VL 17 IS 10 BP 815 EP 821 DI 10.1038/gim.2014.199 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CS9VV UT WOS:000362441900010 PM 25590978 ER PT J AU Abreo, AP Chertow, GM Dalrymple, LS Kaysen, GA Johansen, KL AF Abreo, Adrian P. Chertow, Glenn M. Dalrymple, Lorien S. Kaysen, George A. Johansen, Kirsten L. TI Association of bioimpedance spectroscopy-based volume estimation with postdialysis hypotension in patients receiving hemodialysis SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE Bioimpedance spectroscopy; end-stage renal disease; hemodialysis; volume status ID DRY-WEIGHT; BLOOD-PRESSURE; WHOLE-BODY; MULTIFREQUENCY BIOIMPEDANCE; DIALYSIS PATIENTS; FLUID VOLUME; DYSFUNCTION; REDUCTION; MORTALITY; TRIAL AB Clinical examination to determine the dry weight of patients on hemodialysis (HD) has been problematic, with studies showing discordance between physician assessment and objective measures of volume status.We studied the association between predialysis bioimpedance spectroscopy (BIS)-based estimates of fluid overload and postdialysis hypotension in 635 patients in the United States Renal Data System ACTIVE/ADIPOSE (A Cohort study To Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD) study receiving HD in 2009-2011. We recorded predialysis and postdialysis weight and blood pressures over 3 consecutive HD sessions and performed BIS before a single session. Using a previously reported method of estimating normohydration weight, we estimated postdialysis fluid overload (FOpost) in liters. We used logistic regression with extracellular water/total body water (ECW/TBW) or estimated FOpost as the primary predictor and 1 or more postdialysis systolic blood pressures less than 110mmHg as the dependent variable. Models were adjusted for age, sex, race, ultrafiltration rate per kilogram of body weight, end-stage renal disease vintage, diabetes mellitus, heart failure, and albumin. Higher ECW/TBW was associated with lower odds of postdialysis hypotension (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15-0.84 per 0.1, P=0.02). Every liter of FOpost was associated with lower adjusted odds of postdialysis hypotension (OR 0.86, 95% CI 0.79-0.95, P=0.003). Prospective studies are needed to determine whether this application of BIS could improve current clinical efforts to minimize episodes of postdialysis hypotension without leading to volume overload. C1 [Abreo, Adrian P.] Univ Cincinnati, Coll Med, Div Nephrol, Cincinnati, OH 45267 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Dalrymple, Lorien S.; Kaysen, George A.] Univ Calif Davis, Div Nephrol, Davis, CA 95616 USA. [Kaysen, George A.] Univ Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Abreo, AP (reprint author), Univ Cincinnati, Coll Med, MSB, 231 Albert Sabin Way,G261, Cincinnati, OH 45267 USA. EM adrian.abreo@uc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [N01-DK-7-0005, N01-DK-7-5004]; [K24DK085153]; [K23DK093584] FX This work was supported through contracts N01-DK-7-0005 and N01-DK-7-5004 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a K24DK085153 grant, and a K23DK093584 (LSD) grant. NR 27 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1492-7535 EI 1542-4758 J9 HEMODIAL INT JI Hemodial. Int. PD OCT PY 2015 VL 19 IS 4 BP 536 EP 542 DI 10.1111/hdi.12305 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CT1TN UT WOS:000362584500024 PM 25881673 ER PT J AU Williams, ME Mittman, N Ma, L Brennan, JI Mooney, A Johnson, CD Jani, CM Maddux, FW Lacson, E AF Williams, Mark E. Mittman, Neal Ma, Lin Brennan, Julia I. Mooney, Ann Johnson, Curtis D. Jani, Chinu M. Maddux, Franklin W. Lacson, Eduardo, Jr. TI The Glycemic Indices in Dialysis Evaluation (GIDE) study: Comparative measures of glycemic control in diabetic dialysis patients SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE Clinical nephrology; complications; outcomes research ID HEMOGLOBIN A(1C) LEVELS; CHRONIC KIDNEY-DISEASE; MAINTENANCE HEMODIALYSIS-PATIENTS; CHRONIC-RENAL-FAILURE; GLYCATED ALBUMIN; ERYTHROPOIETIN TREATMENT; LABORATORY ANALYSIS; MANAGEMENT; MELLITUS; RECOMMENDATIONS AB The validity of hemoglobin A1c (HgbA1c) is undergoing increasing scrutiny in the advanced CKD/ESRD (chronic kidney disease/end-stage renal disease) population, where it appears to be discordant from other glycemic indices. In the Glycemic Indices in Dialysis Evaluation (GIDE) Study, we sought to assess correlation of HgbA1c with casual glucose, glycated albumin, and serum fructosamine in a large group of diabetic patients on dialysis. From 26 dialysis facilities in the United States, 1758 diabetic patients (hemodialysis=1476, peritoneal dialysis=282) were enrolled in the first quarter of 2013. The distributions of HgbA1c and the other glycemic indices were analyzed. Intra-patient coefficients of variation and correlations among the four glycemic indices were determined. Patients with low HgbA1c values were both on higher erythropoietin (ESA) doses and more anemic. Serum glucose exhibited the highest intra-patient variability over a 3-month period; variability was modest among the other glycemic indices, and least with HgbA1c. Statistical analyses inclusive of all glycemic markers indicated modest to strong correlations. HgbA1c was more likely to be in the target range than glycated albumin or serum fructosamine, suggesting factors which may or may not be directly related to glycemic control, including anemia, ESA management, and iron administration, in interpreting HgbA1c values. These initial results from the GIDE Study clarify laboratory correlations among glycemic indices and add to concerns about reliance on HgbA1c in patients with diabetes and advanced kidney disease. C1 [Williams, Mark E.] Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. [Mittman, Neal] Kidney Care Brooklyn & Queens, Dept Dialysis, Brooklyn, NY USA. [Ma, Lin; Mooney, Ann; Maddux, Franklin W.; Lacson, Eduardo, Jr.] Fresenius Med Care North Amer, Dept Clin Res, Waltham, MA USA. [Brennan, Julia I.; Johnson, Curtis D.; Jani, Chinu M.] Spectra Labs, Dept Res, Rockleigh, NJ USA. [Brennan, Julia I.; Johnson, Curtis D.; Jani, Chinu M.] Spectra Labs, Milpitas, CA USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 38 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1492-7535 EI 1542-4758 J9 HEMODIAL INT JI Hemodial. Int. PD OCT PY 2015 VL 19 IS 4 BP 562 EP 571 DI 10.1111/hdi.12312 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CT1TN UT WOS:000362584500027 PM 25965145 ER PT J AU Menze, BH Jakab, A Bauer, S Kalpathy-Cramer, J Farahani, K Kirby, J Burren, Y Porz, N Slotboom, J Wiest, R Lanczi, L Gerstner, E Weber, MA Arbel, T Avants, BB Ayache, N Buendia, P Collins, DL Cordier, N Corso, JJ Criminisi, A Das, T Delingette, H Demiralp, C Durst, CR Dojat, M Doyle, S Festa, J Forbes, F Geremia, E Glocker, B Golland, P Guo, XT Hamamci, A Iftekharuddin, KM Jena, R John, NM Konukoglu, E Lashkari, D Mariz, JA Meier, R Pereira, S Precup, D Price, SJ Raviv, TR Reza, SMS Ryan, M Sarikaya, D Schwartz, L Shin, HC Shotton, J Silva, CA Sousa, N Subbanna, NK Szekely, G Taylor, TJ Thomas, OM Tustison, NJ Unal, G Vasseur, F Wintermark, M Ye, DH Zhao, L Zhao, BS Zikic, D Prastawa, M Reyes, M Van Leemput, K AF Menze, Bjoern H. Jakab, Andras Bauer, Stefan Kalpathy-Cramer, Jayashree Farahani, Keyvan Kirby, Justin Burren, Yuliya Porz, Nicole Slotboom, Johannes Wiest, Roland Lanczi, Levente Gerstner, Elizabeth Weber, Marc-Andre Arbel, Tal Avants, Brian B. Ayache, Nicholas Buendia, Patricia Collins, D. Louis Cordier, Nicolas Corso, Jason J. Criminisi, Antonio Das, Tilak Delingette, Herve Demiralp, Cagatay Durst, Christopher R. Dojat, Michel Doyle, Senan Festa, Joana Forbes, Florence Geremia, Ezequiel Glocker, Ben Golland, Polina Guo, Xiaotao Hamamci, Andac Iftekharuddin, Khan M. Jena, Raj John, Nigel M. Konukoglu, Ender Lashkari, Danial Mariz, Jose Antonio Meier, Raphael Pereira, Sergio Precup, Doina Price, Stephen J. Raviv, Tammy Riklin Reza, Syed M. S. Ryan, Michael Sarikaya, Duygu Schwartz, Lawrence Shin, Hoo-Chang Shotton, Jamie Silva, Carlos A. Sousa, Nuno Subbanna, Nagesh K. Szekely, Gabor Taylor, Thomas J. Thomas, Owen M. Tustison, Nicholas J. Unal, Gozde Vasseur, Flor Wintermark, Max Ye, Dong Hye Zhao, Liang Zhao, Binsheng Zikic, Darko Prastawa, Marcel Reyes, Mauricio Van Leemput, Koen TI The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE MRI; Brain; Oncology/tumor; Image segmentation; Benchmark ID MULTIPLE-SCLEROSIS LESIONS; MAGNETIC-RESONANCE IMAGES; CONDITIONAL RANDOM-FIELDS; ATLAS-BASED SEGMENTATION; GRAPH CUTS; MR-IMAGES; DEFORMABLE REGISTRATION; AUTOMATIC SEGMENTATION; UNIFIED SEGMENTATION; ENERGY MINIMIZATION AB In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low-and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource. C1 [Menze, Bjoern H.] Tech Univ Munich, Inst Adv Study, D-80290 Munich, Germany. [Menze, Bjoern H.] Tech Univ Munich, Dept Comp Sci, D-80290 Munich, Germany. [Menze, Bjoern H.; Jakab, Andras; Szekely, Gabor] ETH, Comp Vis Lab, Zurich, Switzerland. [Menze, Bjoern H.] Inria, Asclepios Project, Sophia Antipolis, France. [Menze, Bjoern H.; Golland, Polina; Lashkari, Danial] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Jakab, Andras; Lanczi, Levente] Univ Debrecen, Debrecen, Hungary. [Bauer, Stefan] Univ Bern, Inst Surg Technol & Biomech, CH-3012 Bern, Switzerland. [Bauer, Stefan; Burren, Yuliya; Porz, Nicole; Slotboom, Johannes; Wiest, Roland] Univ Hosp Bern, Inselspital, SCAN, Inst Diagnost & Intervent Neuroradiol, Bern, Switzerland. [Kalpathy-Cramer, Jayashree] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Farahani, Keyvan; Kirby, Justin] NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA. [Gerstner, Elizabeth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurooncol, Boston, MA USA. [Glocker, Ben] Univ London Imperial Coll Sci Technol & Med, BioMedIA Grp, London, England. [Arbel, Tal; Subbanna, Nagesh K.] McGill Univ, Ctr Intelligent Machines, Montreal, PQ H3A 2T5, Canada. [Avants, Brian B.] Univ Penn, Dept Radiol, Penn Image Comp & Sci Lab, Philadelphia, PA 19104 USA. [Ayache, Nicholas; Cordier, Nicolas; Delingette, Herve; Geremia, Ezequiel] INRIA, Asclepios Project, Sophia Antipolis, France. [Buendia, Patricia; John, Nigel M.; Ryan, Michael; Taylor, Thomas J.] INFOTECH Soft Inc, Miami, FL USA. [Collins, D. Louis] McGill Univ, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2T5, Canada. [Corso, Jason J.; Sarikaya, Duygu; Zhao, Liang] SUNY Buffalo, Comp Sci & Engn, Buffalo, NY 14260 USA. [Criminisi, Antonio; Shotton, Jamie; Zikic, Darko] Microsoft Res, Cambridge, England. [Das, Tilak; Jena, Raj; Price, Stephen J.; Thomas, Owen M.] Cambridge Univ Hosp, Cambridge, England. [Demiralp, Cagatay] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. [Dojat, Michel; Doyle, Senan; Forbes, Florence; Vasseur, Flor] INRIA Rhone Alpes, Grenoble, France. [Dojat, Michel; Doyle, Senan; Forbes, Florence; Vasseur, Flor] INSERM, U836, Grenoble, France. [Durst, Christopher R.; Tustison, Nicholas J.; Wintermark, Max] Univ Virginia, Dept Radiol & Med Imaging, Charlottesville, VA USA. [Festa, Joana; Pereira, Sergio; Silva, Carlos A.] Univ Minho, Dept Elect, P-4719 Braga, Portugal. [Guo, Xiaotao; Schwartz, Lawrence; Zhao, Binsheng] Columbia Univ, Dept Radiol, New York, NY USA. [Hamamci, Andac; Unal, Gozde] Sabanci Univ, Fac Engn & Nat Sci, Istanbul, Turkey. [Iftekharuddin, Khan M.; Reza, Syed M. S.] Old Dominion Univ, Dept Elect & Comp Engn, Vis Lab, Norfolk, VA USA. [John, Nigel M.] Univ Miami, Dept Elect & Comp Engn, Coral Gables, FL 33124 USA. [Konukoglu, Ender] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Konukoglu, Ender] Harvard Univ, Sch Med, Boston, MA USA. [Mariz, Jose Antonio; Sousa, Nuno] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga, Portugal. [Mariz, Jose Antonio; Sousa, Nuno] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal. [Meier, Raphael; Reyes, Mauricio] Univ Bern, Inst Surg Technol & Biomech, CH-3014 Bern, Switzerland. [Precup, Doina] McGill Univ, Sch Comp Sci, Montreal, PQ H3A 2T5, Canada. [Precup, Doina] Ben Gurion Univ Negev, Dept Elect & Comp Engn, IL-84105 Beer Sheva, Israel. [Weber, Marc-Andre] Univ Hosp, Diagnost & Intervent Radiol, Heidelberg, Germany. [Ye, Dong Hye] Purdue Univ, Dept Elect & Comp Engn, W Lafayette, IN 47907 USA. [Prastawa, Marcel] GE Global Res, Niskayuna, NY USA. [Van Leemput, Koen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA. [Van Leemput, Koen] Tech Univ Denmark, Lyngby, Denmark. [Van Leemput, Koen] Aalto Univ, Espoo, Finland. RP Menze, BH (reprint author), Tech Univ Munich, Inst Adv Study, D-80290 Munich, Germany. RI Van Leemput, Koen/A-9197-2009; Dojat, Michel/G-7758-2011; Unal, Gozde/A-2360-2013; Weber, Marc-Andre/C-4452-2016; Silva, Carlos/J-1190-2014; Price, Stephen/B-1068-2011; Riklin Raviv, Tammy/A-3462-2013; OI Durst, Christopher/0000-0003-4236-7524; Glocker, Ben/0000-0002-4897-9356; Van Leemput, Koen/0000-0001-6466-5309; Dojat, Michel/0000-0003-2747-6845; Unal, Gozde/0000-0001-5942-8966; Silva, Carlos/0000-0002-1015-5095; Price, Stephen/0000-0002-7535-3009; Cordier, Nicolas/0000-0002-8794-8747; Das, Tilak/0000-0003-0655-412X FU NIH NCRR [P41-RR14075]; NIH NIBIB [R01EB013565]; Academy of Finland [133611]; TEKES (ComBrain); Lundbeck Foundation [R141-2013-13117]; Swiss Cancer League; Swiss Institute for Computer Assisted Surgery (SICAS); NIH NIBIB NAMIC [U54-EB005149]; NIH NCRR NAC [P41-RR13218]; NIH NIBIB NAC [P41-EB-015902]; NIH NCI [R15CA115464]; European Research Council through ERC [MedYMA 2011-291080]; FCT; COMPETE [FCOM-01-0124-FEDER-022674]; MICAT Project (EU) [PIRG-GA-2008-231052]; European Union [600841]; Swiss NSF project Computer Aided and Image Guided Medical Interventions (NCCR CO-ME); Technische Universitat Munchen-Institute for Advanced Study - German Excellence Initiative; Technische Universitat Munchen-Institute for Advanced Study - European Union [291763]; Marie Curie COFUND program of the European Union FX This research was supported by the NIH NCRR (P41-RR14075), the NIH NIBIB (R01EB013565), the Academy of Finland (133611), TEKES (ComBrain), the Lundbeck Foundation (R141-2013-13117), the Swiss Cancer League, the Swiss Institute for Computer Assisted Surgery (SICAS), the NIH NIBIB NAMIC (U54-EB005149), the NIH NCRR NAC (P41-RR13218), the NIH NIBIB NAC (P41-EB-015902), the NIH NCI (R15CA115464), the European Research Council through the ERC Advanced Grant MedYMA 2011-291080 (on Biophysical Modeling and Analysis of Dynamic Medical Images), the FCT and COMPETE (FCOM-01-0124-FEDER-022674), the MICAT Project (EU FP7 Marie Curie Grant No. PIRG-GA-2008-231052), the European Union Seventh Framework Programme under grant agreement no. 600841, the Swiss NSF project Computer Aided and Image Guided Medical Interventions (NCCR CO-ME), the Technische Universitat Munchen-Institute for Advanced Study (funded by the German Excellence Initiative and the European Union Seventh Framework Programme under Grant agreement 291763), the Marie Curie COFUND program of the European Union (Rudolf Mossbauer Tenure-Track Professorship to BHM). NR 132 TC 62 Z9 62 U1 11 U2 42 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD OCT PY 2015 VL 34 IS 10 BP 1993 EP 2024 DI 10.1109/TMI.2014.2377694 PG 32 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA CS8SF UT WOS:000362358000001 PM 25494501 ER PT J AU Noto, MJ Boyd, KL Burns, WJ Varga, MG Peek, RM Skaar, EP AF Noto, Michael J. Boyd, Kelli L. Burns, William J. Varga, Matthew G. Peek, Richard M., Jr. Skaar, Eric P. TI Toll-Like Receptor 9 Contributes to Defense against Acinetobacter baumannii Infection SO INFECTION AND IMMUNITY LA English DT Article ID NEGATIVE BACTERIAL PNEUMONIA; HOST-RESISTANCE; PULMONARY INFECTION; DISEASES-SOCIETY; DENDRITIC CELLS; INNATE IMMUNITY; BAD BUGS; TLR9; CARBAPENEM; DNA AB Acinetobacter baumannii is a common nosocomial pathogen capable of causing severe diseases associated with significant morbidity and mortality in impaired hosts. Pattern recognition receptors, such as the Toll-like receptors (TLRs), play a key role in pathogen detection and function to alert the immune system to infection. Here, we examine the role for TLR9 signaling in response to A. baumannii infection. In a murine model of A. baumannii pneumonia, TLR9(-/)-mice exhibit significantly increased bacterial burdens in the lungs, increased extrapulmonary bacterial dissemination, and more severe lung pathology compared with those in wild-type mice. Following systemic A. baumannii infection, TLR9(-/)-mice have significantly increased bacterial burdens in the lungs, as well as decreased proinflammatory cytokine and chemokine production. These results demonstrate that TLR9-mediated pathogen detection is important for host defense against the opportunistic pathogen Acinetobacter baumannii. C1 [Noto, Michael J.; Burns, William J.; Skaar, Eric P.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37212 USA. [Noto, Michael J.] Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Dept Med, Nashville, TN 37212 USA. [Boyd, Kelli L.; Burns, William J.; Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. [Varga, Matthew G.; Peek, Richard M., Jr.] Vanderbilt Univ, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Nashville, TN 37212 USA. RP Skaar, EP (reprint author), Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37212 USA. EM eric.skaar@vanderbilt.edu OI Varga, Matthew/0000-0002-2075-3224 FU Department of Veterans Affairs merit award [INFB-024-13F]; National Institutes of Health [R01DK58587, R01CA77955, P01CA116087, 2T32HL087738-06] FX This research was supported by Department of Veterans Affairs merit award INFB-024-13F to E.P.S., National Institutes of Health grants R01DK58587, R01CA77955, and P01CA116087 to R.M.P., and National Institutes of Health grant 2T32HL087738-06 to M.J.N. E.P.S. is a Burroughs Wellcome Fellow in the Pathogenesis of Infectious Diseases. NR 48 TC 4 Z9 4 U1 0 U2 5 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 OCT PY 2015 VL 83 IS 10 BP 4134 EP 4141 DI 10.1128/IAI.00410-15 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CT0NJ UT WOS:000362492600034 PM 26238713 ER PT J AU McMillen, RC Gottlieb, MA Winickoff, JP AF McMillen, Robert C. Gottlieb, Mark A. Winickoff, Jonathan P. TI e-Cigarettes-The Roles of Regulation and Clinicians SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [McMillen, Robert C.] Mississippi State Univ, Social Sci Res Ctr, Starkville, MS 39759 USA. [McMillen, Robert C.; Gottlieb, Mark A.; Winickoff, Jonathan P.] Amer Acad Pediat, Julius B Richmond Ctr Excellence, Elk Grove Village, IL USA. [Gottlieb, Mark A.] Northeastern Univ, Sch Law, Publ Hlth Advocacy Inst, Boston, MA 02115 USA. [Winickoff, Jonathan P.] Massachusetts Gen Hosp, Dept Pediat, Div Gen Acad Pediat, Boston, MA 02114 USA. RP McMillen, RC (reprint author), Mississippi State Univ, Social Sci Res Ctr, 103 Res Pk,Ste 103, Starkville, MS 39759 USA. EM rcm19@msstate.edu NR 6 TC 2 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD OCT PY 2015 VL 175 IS 10 BP 1603 EP 1604 DI 10.1001/jamainternmed.2015.4436 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CT1WY UT WOS:000362594600001 PM 26322472 ER PT J AU Balboni, TA Balboni, MJ Fitchett, G AF Balboni, Tracy A. Balboni, Michael J. Fitchett, George TI Religion, Spirituality, and the Intensive Care Unit The Sound of Silence SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID PALLIATIVE CARE; QUALITY; DEATH C1 [Balboni, Tracy A.; Balboni, Michael J.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. [Balboni, Michael J.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Fitchett, George] Rush Univ, Med Ctr, Dept Relig Hlth & Human Values, Chicago, IL 60612 USA. RP Balboni, TA (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave, Boston, MA 02215 USA. EM tbalboni@lroc.harvard.edu NR 8 TC 0 Z9 0 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD OCT PY 2015 VL 175 IS 10 BP 1669 EP 1670 DI 10.1001/jamainternmed.2015.4471 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CT1WY UT WOS:000362594600014 PM 26323044 ER PT J AU Doll, JA Hellkamp, A Ho, PM Kontos, MC Whooley, MA Peterson, ED Wang, TY AF Doll, Jacob A. Hellkamp, Anne Ho, P. Michael Kontos, Michael C. Whooley, Mary A. Peterson, Eric D. Wang, Tracy Y. TI Participation in Cardiac Rehabilitation Programs Among Older Patients After Acute Myocardial Infarction SO JAMA INTERNAL MEDICINE LA English DT Letter ID AMERICAN-HEART-ASSOCIATION; SCIENTIFIC STATEMENT; PREVENTION; CARDIOLOGY C1 [Doll, Jacob A.; Hellkamp, Anne; Peterson, Eric D.; Wang, Tracy Y.] Duke Clin Res Inst, Durham, NC USA. [Doll, Jacob A.; Hellkamp, Anne; Peterson, Eric D.; Wang, Tracy Y.] Duke Univ, Dept Med, Div Cardiol, Durham, NC USA. [Ho, P. Michael] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Ho, P. Michael] Univ Colorado, Sch Med, Dept Med, Div Cardiol, Aurora, CO USA. [Kontos, Michael C.] Virginia Commonwealth Univ, Dept Med, Div Cardiol, Richmond, VA 23284 USA. [Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. RP Doll, JA (reprint author), 2400 Pratt St, Durham, NC 27705 USA. EM jacob.doll@duke.edu FU AHRQ HHS [U19HS021092] NR 7 TC 9 Z9 9 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD OCT PY 2015 VL 175 IS 10 BP 1700 EP 1702 DI 10.1001/jamainternmed.2015.3819 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CT1WY UT WOS:000362594600022 PM 26237309 ER PT J AU Riley, LE AF Riley, Laura E. TI Ensuring a Diverse Physician Workforce: Progress but More to Be Done SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID ACADEMIC MEDICINE; BLACK; RACE C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Riley, LE (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 32 Fruit St, Boston, MA 02114 USA. EM lriley@mgh.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD OCT PY 2015 VL 175 IS 10 BP 1708 EP 1709 DI 10.1001/jamainternmed.2015.4333 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CT1WY UT WOS:000362594600026 PM 26301316 ER PT J AU Khan, RF Feder, S Goldstein, NE Chaudhry, SI AF Khan, Rabeea F. Feder, Shelli Goldstein, Nathan E. Chaudhry, Sarwat I. TI Symptom Burden Among Patients Who Were Hospitalized for Heart Failure SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Khan, Rabeea F.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. [Feder, Shelli] Yale Univ, Sch Nursing, New Haven, CT 06520 USA. [Goldstein, Nathan E.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Goldstein, Nathan E.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Chaudhry, Sarwat I.] Yale Univ, Sch Med, Dept Internal Med, Gen Internal Med Sect, New Haven, CT 06520 USA. RP Chaudhry, SI (reprint author), Yale Univ, Sch Med, Dept Internal Med, Gen Internal Med Sect, Harkness Off Bldg,367 Cedar St,Room 416, New Haven, CT 06520 USA. NR 5 TC 3 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD OCT PY 2015 VL 175 IS 10 BP 1713 EP 1715 DI 10.1001/jamainternmed.2015.3871 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CT1WY UT WOS:000362594600029 PM 26280896 ER PT J AU Falvey, JR Burke, RE Stevens-Lapsley, JE AF Falvey, Jason R. Burke, Robert E. Stevens-Lapsley, Jennifer E. TI Physical Function and Hospital Readmissions SO JAMA INTERNAL MEDICINE LA English DT Letter ID DISCHARGE; ELDERS C1 [Falvey, Jason R.; Stevens-Lapsley, Jennifer E.] Univ Colorado, Dept Phys Med & Rehabil, Phys Therapy Program, Aurora, CO 80045 USA. [Burke, Robert E.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Burke, Robert E.] Univ Colorado, Sch Med, Aurora, CO 80045 USA. RP Falvey, JR (reprint author), Univ Colorado, Dept Phys Med & Rehabil, Phys Therapy Program, 13121 E 17th Ave,Anschutz Med Campus, Aurora, CO 80045 USA. EM Jason.Falvey@ucdenver.edu FU NCATS NIH HHS [UL1 TR001082] NR 9 TC 0 Z9 0 U1 3 U2 3 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 OCT PY 2015 VL 175 IS 10 BP 1722 EP 1723 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CT1WY UT WOS:000362594600039 PM 26436745 ER PT J AU Kutner, JS Ritchie, CS Abernethy, AP AF Kutner, Jean S. Ritchie, Christine S. Abernethy, Amy P. TI Selecting the Optimal Design for Drug Discontinuation Trials in a Setting of Advanced, Life-Limiting Illness Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Kutner, Jean S.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Ritchie, Christine S.] Jewish Home San Francisco, Ctr Res Aging, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Ritchie, Christine S.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Abernethy, Amy P.] Duke Univ, Sch Med, Duke Clin Res Inst, Ctr Learning Hlth Care, Durham, NC USA. RP Abernethy, AP (reprint author), Duke Univ, Med Ctr, POB 3436, Durham, NC 27710 USA. EM amy.abernethy@duke.edu FU NINR NIH HHS [UC4-NR012584, U24-NR014637] NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD OCT PY 2015 VL 175 IS 10 BP 1725 EP 1726 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CT1WY UT WOS:000362594600044 PM 26436751 ER PT J AU Etheredge, AJ Premji, Z Gunaratna, NS Abioye, AI Aboud, S Duggan, C Mongi, R Meloney, L Spiegelman, D Roberts, D Hamer, DH Fawzi, WW AF Etheredge, Analee J. Premji, Zul Gunaratna, Nilupa S. Abioye, Ajibola Ibraheem Aboud, Said Duggan, Christopher Mongi, Robert Meloney, Laura Spiegelman, Donna Roberts, Drucilla Hamer, Davidson H. Fawzi, Wafaie W. TI Iron Supplementation in Iron-Replete and Nonanemic Pregnant Women in Tanzania A Randomized Clinical Trial SO JAMA PEDIATRICS LA English DT Article ID PLASMODIUM-FALCIPARUM INFECTION; PLACENTAL MALARIA; BIRTH-WEIGHT; PROPHYLACTIC IRON; ANEMIA; RISK; MORTALITY; OUTCOMES; ROUTINE; AFRICA AB IMPORTANCE Anemia is common in pregnancy and increases the risk of adverse outcomes. Iron deficiency is a leading cause of anemia in sub-Saharan Africa, and iron supplementation is the standard of care during pregnancy; however, recent trials among children have raised concerns regarding the safety of iron supplementation in malaria-endemic regions. There is limited evidence on the safety of iron supplementation during pregnancy in these areas. OBJECTIVE To evaluate the safety and efficacy of iron supplementation during pregnancy in a malaria-endemic region. DESIGN, SETTING, AND PARTICIPANTS We conducted a randomized, double-blind, placebo-controlled clinical trial among pregnant women presenting for antenatal care in Dar es Salaam, Tanzania, from September 28, 2010, through October 4, 2012. Iron-replete, nonanemic women were eligible if they were uninfected with human immunodeficiency virus, primigravidae or secundigravidae, and at or before 27 weeks of gestation. Screening of 21 316 women continued until the target enrollment of 1500 was reached. Analyses followed the intent-to-treat principle and included all randomized participants. INTERVENTIONS Participants were randomized to receive 60 mg of iron or placebo, returning every 4 weeks for standard prenatal care, including malaria screening, prophylaxis with the combination of sulfadoxine and pyrimethamine, and treatment, as needed. MAIN OUTCOMES AND MEASURES The primary outcomes were placental malaria, maternal hemoglobin level at delivery, and birth weight. RESULTS Among 1500 study participants (750 randomized for each group), 731 in iron group and 738 in placebo group had known birth outcomes and 493 in iron group and 510 in placebo group had placental samples included in the analysis. Maternal characteristics were similar at baseline in the iron and placebo groups, and 1354 (91.7%) used malaria control measures. The risk of placental malaria was not increased by maternal iron supplementation (relative risk [RR], 1.03; 95% CI, 0.65-1.65), and iron supplementation did not significantly affect birth weight (3155 vs 3137 g, P = .89). Compared with placebo, iron supplementation significantly improved the mean increase from baseline to delivery for hemoglobin (0.1 vs -0.7 g/dL, P < .001) and serum ferritin (41.3 vs 11.3 mu g/L, P < .001). Iron supplementation significantly decreased the risk of anemia at delivery by 40% (RR, 0.60; 95% CI, 0.51-0.71) but not severe anemia (RR, 0.68; 95% CI, 0.41-1.14). Iron supplementation significantly reduced the risk of maternal iron deficiency at delivery by 52% (RR, 0.48; 95% CI, 0.32-0.70) and the risk of iron deficiency anemia by 66% (RR, 0.34; 95% CI, 0.19-0.62). CONCLUSIONS AND RELEVANCE Prenatal iron supplementation among iron-replete, nonanemic women was not associated with an increased risk of placental malaria or other adverse events in the context of good malaria control. Participants receiving supplementation had improved hematologic and iron status at delivery compared with the placebo group. These findings provide support for continued administration of iron during pregnancy in malaria-endemic regions. C1 [Etheredge, Analee J.; Gunaratna, Nilupa S.; Abioye, Ajibola Ibraheem; Duggan, Christopher; Meloney, Laura; Fawzi, Wafaie W.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Etheredge, Analee J.; Duggan, Christopher] Harvard Univ, Sch Med, Div Gastroenterol Hepatol & Nutr, Boston Childrens Hosp, Boston, MA 02115 USA. [Premji, Zul; Mongi, Robert] Muhimbili Univ Hlth & Allied Sci, Sch Publ Hlth & Social Sci, Dept Parasitol Med Entomol, Dar Es Salaam, Tanzania. [Aboud, Said] Muhimbili Univ Hlth & Allied Sci, Dept Microbiol & Immunol, Dar Es Salaam, Tanzania. [Duggan, Christopher; Spiegelman, Donna; Fawzi, Wafaie W.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Spiegelman, Donna; Fawzi, Wafaie W.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hamer, Davidson H.] Boston Univ, Sch Publ Hlth, Dept Global Hlth, Boston, MA USA. [Roberts, Drucilla] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hamer, Davidson H.] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02215 USA. [Hamer, Davidson H.] Boston Med Ctr, Dept Med, Infect Dis Sect, Boston, MA USA. RP Fawzi, WW (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave,Bldg 1,Room 1102, Boston, MA 02115 USA. EM mina@hsph.harvard.edu OI Etheredge, Analee/0000-0001-6102-2754 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 HD061232, 1K24HD058795] FX This study was supported by grants U01 HD061232 (Dr Fawzi) and 1K24HD058795 (Dr Duggan) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 45 TC 6 Z9 6 U1 6 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD OCT PY 2015 VL 169 IS 10 BP 947 EP 955 DI 10.1001/jamapediatrics.2015.1480 PG 9 WC Pediatrics SC Pediatrics GA CT1XJ UT WOS:000362595700015 PM 26280534 ER PT J AU Perrin, JM AF Perrin, James M. TI Bringing Innovation to Attention-Deficit Hyperactivity Disorder Care SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material DE ADHD; chronic care; group visits; payment reform ID CLINICAL-PRACTICE GUIDELINE; DEFICIT/HYPERACTIVITY DISORDER; HEALTH-CARE; CHILDREN C1 [Perrin, James M.] Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children, Boston, MA 02115 USA. RP Perrin, JM (reprint author), MassGen Hosp Children, 125 Nashua St,860, Boston, MA 02114 USA. EM jperrin@mgh.harvard.edu NR 8 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 2015 VL 36 IS 8 BP 635 EP 636 DI 10.1097/DBP.0000000000000223 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA CT1FX UT WOS:000362544300011 PM 26414091 ER PT J AU Claessen, FMAP Braun, Y Peters, RM Kolovich, GP Ring, D AF Claessen, Femke M. A. P. Braun, Yvonne Peters, Rinne M. Kolovich, Gregory P. Ring, David TI Plate and Screw Fixation of Bicolumnar Distal Humerus Fractures: Factors Associated With Loosening or Breakage of Implants or Nonunion SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Elbow trauma; distal humerus fracture; nonunion; failure of fixation ID SURGICAL-TREATMENT; INTERNAL-FIXATION; RISK-FACTORS; MANAGEMENT; ADULTS; INJURIES; FAILURE AB Purpose To identify factors associated with reoperation for early loosening or breakage of implants or nonunion after operative treatment of AO type C distal humerus fractures. Methods We retrospectively analyzed 129 adult patients who had operative treatment of an isolated AO type C distal humerus fracture at 1 of 5 hospitals to determine factors associated with reoperation for early loosening or breakage of implants or nonunion. Results Within 6 months of original fixation, 16 of 129 fractures (12%) required reoperation for loosening or breakage of implants (n = 8) or nonunion (n = 8). In bivariate analyses, the Charlson comorbidity index, smoking, a coded diagnosis of obesity, diabetes mellitus, and radiographic osteoarthritis were significantly associated with reoperation for early loosening or breakage of implants or nonunion. Conclusions With the numbers available, patient factors rather than technical factors were associated with reoperation for loosening or breakage of implants and nonunion. Because of the relative infrequency of fixation problems and nonunion, a much larger study is needed to address technical deficiencies. (J Hand Surg Am. 2015;40(10):2045-2051. Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Claessen, Femke M. A. P.; Braun, Yvonne; Peters, Rinne M.; Kolovich, Gregory P.; Ring, David] Massachusetts Gen Hosp, Dept Hand Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 23 TC 0 Z9 0 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2015 VL 40 IS 10 BP 2045 EP 2051 DI 10.1016/j.jhsa.2015.07.009 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CT2HC UT WOS:000362621600016 PM 26319772 ER PT J AU Jupiter, JB AF Jupiter, Jesse B. TI Letter Regarding "Modalities for Complex Regional Pain Syndrome" SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2015 VL 40 IS 10 BP 2115 EP 2116 DI 10.1016/j.jhsa.2015.07.014 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CT2HC UT WOS:000362621600029 PM 26408380 ER PT J AU Raizman, NM Ring, DC AF Raizman, Noah M. Ring, David C. TI Letter Regarding "Thumb Ligament Injuries" SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter ID GAMEKEEPERS THUMB C1 [Raizman, Noah M.] Ctr Adv Orthopaed, Washington, DC 20036 USA. [Ring, David C.] Massachusetts Gen Hosp, Dept Hand Surg, Boston, MA 02114 USA. RP Raizman, NM (reprint author), Ctr Adv Orthopaed, Washington, DC 20036 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2015 VL 40 IS 10 BP 2116 EP 2117 DI 10.1016/j.jhsa.2015.06.124 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CT2HC UT WOS:000362621600031 PM 26408383 ER PT J AU Yevchak, AM Doherty, K Archambault, EG Kelly, B Fonda, JR Rudolph, JL AF Yevchak, Andrea M. Doherty, Kelly Archambault, Elizabeth G. Kelly, Brittany Fonda, Jennifer R. Rudolph, James L. TI The association between an ultrabrief cognitive screening in older adults and hospital outcomes SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review ID CONFUSION ASSESSMENT METHOD; AGITATION-SEDATION SCALE; FUTURE-DIRECTIONS; ALZHEIMER-DISEASE; ELDERLY-PATIENTS; CARDIAC-SURGERY; DELIRIUM; CARE; VALIDATION; DEMENTIA AB BACKGROUNDThough often recommended, hospital cognitive assessment is infrequently completed due to clinical and time constraints. OBJECTIVEThis analysis aimed to evaluate the relationship between performance on ultrabrief cognitive screening instruments and hospital outcomes. DESIGNThis is a secondary data analysis of a quality improvement project. SETTINGTertiary Veterans Administration hospital in New England. PATIENTSPatients,60 years old, admitted to the hospital. INTERVENTIONNone. MEASUREMENTSUpon admission, patients were administered 2 cognitive screening tools. The modified Richmond Agitation and Sedation Scale (mRASS) is a measure of arousal that can be completed in 15 seconds. The months of the year backward (MOYB) is a measure of attention that can be administered in 1 minute. In-hospital outcomes included restraints and mortality, whereas discharge outcomes included length of stay, discharge not home, and variable direct costs. Risk ratios were calculated for dichotomous outcomes and unadjusted Poisson regression for continuous outcomes. RESULTSPatients (n=3232) were screened. Altered arousal occurred in 15% of patients (n=495); incorrect MOYB was recorded in 45% (n=1457). Relative to those with normal arousal and attention, those with abnormal mRASS and incorrect MOYB had increased length of stay (incident rate ratio [IRR]: 1.23, 95% confidence interval [CI]: 1.17-1.30); restraint use (risk ratio [RR]: 5.05, 95% CI: 3.29-7.75), in-hospital mortality (RR: 3.46, 95% CI: 1.24-9.63), and decreased discharge home (RR: 2.97, 95% CI: 2.42-3.64). Hospital variable direct costs were slightly, but not significantly, higher (IRR: 1.02, 95% CI: 0.88-1.17). CONCLUSIONImpaired performance on ultrabrief cognitive assessments of arousal and attention provide valuable insights regarding hospital outcomes. Journal of Hospital Medicine 2015;10:651-657. 2015 Society of Hospital Medicine C1 [Yevchak, Andrea M.] Penn State Univ, Coll Nursing, University Pk, PA 16802 USA. [Doherty, Kelly; Archambault, Elizabeth G.; Kelly, Brittany; Fonda, Jennifer R.; Rudolph, James L.] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. [Kelly, Brittany] Regis Coll, Sch Nursing Sci & Hlth Profess, Boston, MA USA. [Fonda, Jennifer R.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Rudolph, James L.] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst GRECC, 150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org FU Department of Veterans Affairs Office of Patient Safety Delirium Patient Safety Center of Inquiry; Geriatrics and Extended Care T21 Alternative to Non-institutional Long Term Care award; VA Career Development Award FX Dr. Yevchak and Ms. Doherty contributed equally to this article and agreed to share first authorship. This material is based upon work supported by the Department of Veterans Affairs Office of Patient Safety Delirium Patient Safety Center of Inquiry and a Geriatrics and Extended Care T21 Alternative to Non-institutional Long Term Care award. Archambault, Doherty, Fonda, Kelly, and Rudolph are employees of the US government. Dr. Rudolph also received support from a VA Career Development Award. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. The authors report no conflicts of interest. NR 41 TC 5 Z9 5 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD OCT PY 2015 VL 10 IS 10 BP 651 EP 657 DI 10.1002/jhm.2450 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CS9XE UT WOS:000362445900002 PM 26374602 ER PT J AU Whitney, J Hill, AL Sanisetty, S Penaloza-MacMaster, P Shetty, M Parenteau, L Cabral, C Shields, J Blackmore, S Smith, JY Brinkman, AL Peter, LE Mathew, SI Smith, KM Borducchi, EN Rosenbloom, DIS Lewis, MG Hattersley, J Li, B Hesselgesser, J Geleziunas, R Robb, ML Kim, JH Michael, NL Barouch, DH AF Whitney, James Hill, Alison L. Sanisetty, Srisowmya Penaloza-MacMaster, Pablo Shetty, Mayuri Parenteau, Lily Cabral, Crystal Shields, Jennifer Blackmore, Stephen Smith, Jeffrey Y. Brinkman, Amanda L. Peter, Lauren E. Mathew, Sheeba I. Smith, Kaitlin M. Borducchi, Erica N. Rosenbloom, Daniel I. S. Lewis, Mark G. Hattersley, Jillian Li, Bei Hesselgesser, Joseph Geleziunas, Romas Robb, Merlin L. Kim, Jerome H. Michael, Nelson L. Barouch, Dan H. TI RAPID ESTABLISHMENT OF THE VIRAL RESERVOIR PRIOR TO SYSTEMIC VIREMIA FOLLOWING MUCOSAL SIV INFECTION OF RHESUS MONKEYS SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Whitney, James; Hill, Alison L.; Sanisetty, Srisowmya; Penaloza-MacMaster, Pablo; Shetty, Mayuri; Parenteau, Lily; Cabral, Crystal; Shields, Jennifer; Blackmore, Stephen; Smith, Jeffrey Y.; Brinkman, Amanda L.; Peter, Lauren E.; Mathew, Sheeba I.; Smith, Kaitlin M.; Borducchi, Erica N.; Rosenbloom, Daniel I. S.; Lewis, Mark G.; Hattersley, Jillian; Li, Bei; Hesselgesser, Joseph; Geleziunas, Romas; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Barouch, Dan H.] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0047-2565 EI 1600-0684 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2015 VL 44 IS 5 SI SI MA O1.07 BP 308 EP 309 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA CS3IM UT WOS:000361966000020 ER PT J AU Veazey, R Pilch-Cooper, H Hope, T Carias, A Rodriguez, B Sieg, S Alter, G Lederman, M AF Veazey, Ronald Pilch-Cooper, Heather Hope, Thomas Carias, Ann Rodriguez, Benigno Sieg, Scott Alter, Galit Lederman, Michael TI PREVENTION OF VAGINAL SHIV ACQUISITION BY TOPICAL IFN-B TREATMENT SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Veazey, Ronald] Tulane Natl Primate Res Ctr, Covington, LA USA. [Pilch-Cooper, Heather; Rodriguez, Benigno; Sieg, Scott; Lederman, Michael] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Hope, Thomas] Northwestern Univ, Chicago, IL 60611 USA. [Alter, Galit] Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0047-2565 EI 1600-0684 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2015 VL 44 IS 5 SI SI MA O3.01 BP 314 EP 314 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA CS3IM UT WOS:000361966000036 ER PT J AU Gommet, C Bernard-Stoecklin, S Cosma, A Dereuddre-Bosquet, N Le Grand, R AF Gommet, Celine Bernard-Stoecklin, Sibylle Cosma, Antonio Dereuddre-Bosquet, Nathalie Le Grand, Roger TI INNATE AND ADAPTIVE RESPONSES IN SEMEN OF SIV INFECTED MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Gommet, Celine; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger] CEA, Div Immunovirol IMETI, Fontenay Aux Roses, France. [Bernard-Stoecklin, Sibylle] Massachussets Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0047-2565 EI 1600-0684 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2015 VL 44 IS 5 SI SI MA O5.02 BP 320 EP 320 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA CS3IM UT WOS:000361966000053 ER PT J AU Radulovic, M Anand, P Korsten, MA Gong, B AF Radulovic, Miroslav Anand, Preeti Korsten, Mark A. Gong, Bing TI Targeting Ion Channels: An Important Therapeutic Implication in Gastrointestinal Dysmotility in Patients With Spinal Cord Injury SO JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Review DE Dysmotility; Gastrointestinal; Interstitial cells of Cajal; Ion channels; Myocytes, smooth muscle ID SENSITIVE K+ CHANNELS; COLONIC SMOOTH-MUSCLE; PROTEIN-KINASE-C; INTERSTITIAL-CELLS; POTASSIUM CHANNELS; SMALL-INTESTINE; INHIBITORY NEUROTRANSMISSION; PACEMAKER ACTIVITY; MURINE COLON; GUINEA-PIG AB Gastrointestinal (GI) dysmotility is a severe, and common complication in patients with spinal cord injury (SCI). Current therapeutic methods using acetylcholine analogs or laxative agents have unwanted side effects, besides often fail to have desired effect. Various ion channels such as ATP-sensitive potassium (K-ATP) channel, calcium ions (Ca2+)-activated potassium ions (K+) channels, voltage-sensitive Ca2+ channels and chloride ion (Cl-) channels are abundantly expressed in GI tissues, and play an important role in regulating GI motility. The release of neurotransmitters from the enteric nerve terminal, innervating GI interstitial cells of Cajal (ICC), and smooth muscle cells (SMC), causes inactivation of K+ and Cl- channels, increasing Ca2+ influx into cytoplasm, resulting in membrane depolarization and smooth muscle contraction. Thus, agents directly regulating ion channels activity either in ICC or in SMC may affect GI peristalsis and would be potential therapeutic target for the treatment of GI dysmotility with SCI. C1 [Radulovic, Miroslav; Korsten, Mark A.; Gong, Bing] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Anand, Preeti; Gong, Bing] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Radulovic, Miroslav; Korsten, Mark A.] James J Peters Vet Affairs Med Ctr, Natl Ctr Excellence Med Consequences SCI, Bronx, NY USA. RP Gong, B (reprint author), Icahn Sch Med Mt Sinai, Dept Med, One Gustave L Levy Placc, New York, NY 10029 USA. EM bing.gong@va.gov FU US Department of Veterans Affairs; Alzheimer's Association [IIRG-12-242345] FX This paper is supported by a grant from US Department of Veterans Affairs to Miroslav Radulovic and Mark A Korsten, and by a grant from Alzheimer's Association (IIRG-12-242345) to Bing Gong. NR 61 TC 0 Z9 1 U1 1 U2 1 PU KOREAN SOC NEUROGASTROENTEROLOGY & MOTILITY PI GANGNAM-GU PA RM 305, LOTTE GOLD ROSE VILL II, 31 SEOLLEUNG-RO 86-GIL, GANGNAM-GU, SEOUL 135-839, SOUTH KOREA SN 2093-0879 EI 2093-0887 J9 J NEUROGASTROENTEROL JI J. Neurogastroenterol. Motil. PD OCT PY 2015 VL 21 IS 4 BP 494 EP 502 DI 10.5056/jnm15061 PG 9 WC Gastroenterology & Hepatology; Clinical Neurology SC Gastroenterology & Hepatology; Neurosciences & Neurology GA CT3GT UT WOS:000362695900006 PM 26424038 ER PT J AU Oliveira, BL Blasi, F Rietz, TA Rotile, NJ Day, H Caravan, P AF Oliveira, Bruno L. Blasi, Francesco Rietz, Tyson A. Rotile, Nicholas J. Day, Helen Caravan, Peter TI Multimodal Molecular Imaging Reveals High Target Uptake and Specificity of In-111- and Ga-68-Labeled Fibrin-Binding Probes for Thrombus Detection in Rats SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE thrombosis; fibrin; PET; SPECT ID CONTRAST AGENTS; PET PROBES; IN-VIVO; FEASIBILITY; ARTERIAL; EP-2104R; SPECT AB We recently showed the high target specificity and favorable imaging properties of Cu-64 and AI(18)F PET probes for noninvasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with Ga-68, In-111, or Tc-99m as thrombus imaging agents for PET and SPECT. In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in 2 animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging. Methods: Radiotracers were synthesized using a known fibrin-binding peptide conjugated to 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DOTA-MA), or a diethylenetriamine ligand (DETA-propanoic acid [PA]), followed by labeling with Ga-68 (FBP14, Ga-68-NODAGA), In-111 (FBP15, In-111-DOTA-MA), or Tc-99m (FBP16, Tc-99m(CO)(3)-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics, and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed I-125-labeled thrombi and with a nonbinding control probe using SPECT/PET/CT imaging. Results: All 3 radiotracers showed affinity similar to soluble fibrin fragment DD(E) (inhibition constant = 0.53-0.83 mu M). After the kidneys, the highest uptake of Ga-68-FBP14 and In-111-FBP15 was in the thrombus (1.0 +/- 0.2 percentage injected dose per gram), with low off-target accumulation. Both radiotracers underwent fast systemic elimination (half-life, 8-15 min) through the kidneys, which led to highly conspicuous thrombi on PET and SPECT images. Tc-99m-FBP16 displayed low target uptake and distribution consistent with aggregation or degradation. Triple-isotope imaging experiments showed that both Ga-68-FBP14 and In-111-FBP15, but not the nonbinding derivative Cu-64-D-Cys-FBP8, detected the location of the 1251-labeled thrombus, confirming high target specificity. Conclusion: Ga-68-FBP14 and In-111-FBP15 have high fibrin affinity and thrombus specificity and represent useful PET and SPECT probes for thrombus detection. C1 [Oliveira, Bruno L.; Blasi, Francesco; Rietz, Tyson A.; Rotile, Nicholas J.; Day, Helen; Caravan, Peter] Harvard Univ, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Med Sch,Massachusetts Gen Hosp, Charlestown, MA USA. [Caravan, Peter] Massachusetts Gen Hosp, Inst Innovat Imaging, Boston, MA 02114 USA. RP Caravan, P (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St,Ste 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu OI Oliveira, Bruno/0000-0002-7687-4746 FU NCRR NIH HHS [RR029495, S10 RR029495]; NHLBI NIH HHS [HL109448, R01 HL109448]; NIH HHS [S10 OD010650] NR 28 TC 0 Z9 0 U1 2 U2 12 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 2015 VL 56 IS 10 BP 1587 EP 1592 DI 10.2967/jnumed.115.160754 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CS9DF UT WOS:000362388600023 PM 26251420 ER PT J AU Van Rompay, MI McKeown, NM Goodman, E Eliasziw, M Chomitz, VR Gordon, CM Economos, CD Sacheck, JM AF Van Rompay, Maria I. McKeown, Nicola M. Goodman, Elizabeth Eliasziw, Misha Chomitz, Virginia R. Gordon, Catherine M. Economos, Christina D. Sacheck, Jennifer M. TI Sugar-Sweetened Beverage Intake Is Positively Associated with Baseline Triglyceride Concentrations, and Changes in Intake Are Inversely Associated with Changes in HDL Cholesterol over 12 Months in a Multi-Ethnic Sample of Children SO JOURNAL OF NUTRITION LA English DT Article DE dyslipidemias; sweetening agents; ethnic groups; health status disparities; child ID FOOD FREQUENCY QUESTIONNAIRE; CARDIOMETABOLIC RISK-FACTORS; BLOCK KIDS QUESTIONNAIRE; UNITED-STATES; CONSUMPTION PATTERNS; INSULIN-RESISTANCE; DRINK CONSUMPTION; PHYSICAL-ACTIVITY; YOUNG-CHILDREN; BLOOD-PRESSURE AB Background: Intake of sugar-sweetened beverages (SSBs) is linked to greater cardiometabolic risk in adults. Although longitudinal evidence is sparse among children, SSB intake reduction is targeted to reduce cardiometabolic risk factors in this group. Objective: We investigated characteristics associated with consumption of SSBs in a multi-ethnic sample of children/ adolescents and measured cross-sectional and longitudinal associations between SSB intake and plasma HDL cholesterol and triglycerides (TGs) over 12 mo. Methods: In a diverse cohort of children aged 8-15 y, cross-sectional associations (n = 613) between baseline SSB intake and blood lipid concentrations and longitudinal associations (n = 380) between mean SSB intake, changes in SSB intake, and lipid changes over 12 mo were assessed with multivariable linear regression. Results: Greater SSB intake was associated with lower socioeconomic status, higher total energy intake, lower fruit/vegetable intake, and more sedentary time. In cross-sectional analysis, greater SSB intake was associated with higher plasma TG concentrations among consumers (62.4, 65.3, and 71.6 mg/dL in children who consumed >0 but <2, >= 2 but <7, and >= 7 servings/wk, respectively; P-trend: 0.03); plasma HDL cholesterol showed no cross-sectional association. In the longitudinal analysis, mean SSB intake over 12 mo was not associated with lipid changes; however, the 12-mo increase in plasma HDLcholesterol concentration was greater among children who decreased their intake by >= 1 serving/wk (4.6 +/- 0.8 mg/dL) compared with children whose intake stayed the same (2.0 +/- 0.8 mg/dL) or increased (1.5 +/- 0.8 mg/dL; P = 0.02). Conclusions: In a multi-ethnic sample of children, intake of SSBs was positively associated with TG concentrations among consumers, and changes in SSB intake were inversely associated with HDL cholesterol concentration changes over 12 mo. Further research in large diverse samples of children is needed to study the public health implications of reducing SSB intake among children of different raciaVethnic groups. The Daily D Health Study was registered at clinicaltnals.gov as NCT01537809. C1 [Van Rompay, Maria I.; Economos, Christina D.; Sacheck, Jennifer M.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [McKeown, Nicola M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Sch Med, Boston, MA 02111 USA. [Eliasziw, Misha; Chomitz, Virginia R.] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. [Goodman, Elizabeth] MassGen Hosp Children, Boston, MA USA. [Goodman, Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. [Gordon, Catherine M.] Brown Univ, Hasbro Childrens Hosp, Alpert Med Sch, Div Adolescent Med, Providence, RI 02912 USA. [Gordon, Catherine M.] Brown Univ, Hasbro Childrens Hosp, Alpert Med Sch, Div Endocrinol, Providence, RI 02912 USA. RP Van Rompay, MI (reprint author), Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. EM maria.vanrompay@tufts.edu FU NIH National Heart, Lung, and Blood Institute [R01HL106160] FX Supported by NIH National Heart, Lung, and Blood Institute grant R01HL106160. NR 52 TC 0 Z9 0 U1 1 U2 4 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD OCT PY 2015 VL 145 IS 10 BP 2389 EP 2395 DI 10.3945/jn.115.212662 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CS9CW UT WOS:000362387700027 PM 26338888 ER PT J AU Zachek, CM Miller, MD Hsu, C Schiffman, JD Sallan, S Metayer, C Dahl, GV AF Zachek, Christine M. Miller, Mark D. Hsu, Christopher Schiffman, Joshua D. Sallan, Stephen Metayer, Catherine Dahl, Gary V. TI Children's Cancer and Environmental Exposures: Professional Attitudes and Practices SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE pediatric hematology; oncology; epidemiology; translational research; medical education; pediatric environmental health ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DAY-CARE ATTENDANCE; CHILDHOOD LEUKEMIA; HEALTH-PROFESSIONALS; IONIZING-RADIATION; RESPONSE RATES; DNA-REPAIR; RISK; PEDIATRICIANS; PESTICIDES AB Background:Epidemiologic studies worldwide have provided substantial evidence of the contributions of environmental exposures to the development of childhood cancer, yet this knowledge has not been integrated into the routine practice of clinicians who care for children with this disease. To identify the basis of this deficit, we sought to assess the environmental history-taking behavior and perceptions of environmental health among pediatric hematologists and oncologists.Procedure:A web-based survey was sent from June to October 2012 to 427 pediatric oncologists, fellows, and nurse practitioners from 20 US institutions, with an overall response rate of 45%.Results:Survey responses indicated that environmental exposures are of concern to clinicians. The vast majority of respondents (88%) reported receiving questions from families about the relationship between certain environmental exposures and the cancers they regularly treat. However, a lack of comfort with these topics seems to have limited their discussions with families about the role of environmental exposures in childhood cancer pathogenesis. Although 77% of respondents suspected that some of the cases they saw had an environmental origin, their methods of taking environmental histories varied widely. Over 90% of respondents believed that more knowledge of the associations between environmental exposures and childhood cancer would be helpful in addressing these issues with patients.Conclusions:Although limited in size and representativeness of participating institutions, the results of this survey indicate a need for increased training for hematology/oncology clinicians about environmental health exposures related to cancer and prompt translation of emerging research findings in biomedical journals that clinicians read. C1 [Zachek, Christine M.; Miller, Mark D.] Univ Calif San Francisco, Western States Pediat Environm Hlth Specialty Uni, San Francisco, CA 94143 USA. [Miller, Mark D.; Metayer, Catherine; Dahl, Gary V.] Univ Calif Berkeley, Ctr Integrat Res Childhood Leukemia & Environm, Berkeley, CA 94720 USA. [Hsu, Christopher; Dahl, Gary V.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Schiffman, Joshua D.] Univ Utah, Dept Pediat, Huntsman Canc Inst, Salt Lake City, UT USA. [Sallan, Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Miller, MD (reprint author), 1515 Clay St,16th Floor, Oakland, CA 94612 USA. EM pehsu@ucsf.edu FU National Institutes of Health (NIEHS)/EPA award [1P01ES018172-01, RD83451101]; Agency for Toxic Substances and Disease Registry (ATSDR) [1 U61TS000238-01] FX Supported by the National Institutes of Health (NIEHS)/EPA award numbers 1P01ES018172-01 (NIEHS)/RD83451101 (USEPA). M. Miller and C. Zachek were also supported for this publication by the cooperative agreement award number 1 U61TS000238-01 from the Agency for Toxic Substances and Disease Registry (ATSDR). Its contents are the responsibility of the authors and do not necessarily represent the official views of the Agency for Toxic Substances and Disease Registry (ATSDR). Neither EPA nor ATSDR endorse the purchase of any commercial products or services mentioned in PEHSU publications. NR 61 TC 5 Z9 5 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1077-4114 EI 1536-3678 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD OCT PY 2015 VL 37 IS 7 BP 491 EP 497 DI 10.1097/MPH.0000000000000416 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CT1GL UT WOS:000362545900001 PM 26334434 ER PT J AU Dabscheck, G Silverman, L Ullrich, NJ AF Dabscheck, Gabriel Silverman, Lewis Ullrich, Nicole J. TI Bacillus cereus Cerebral Abscess During Induction Chemotherapy for Childhood Acute Leukemia SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Editorial Material DE Bacillus cereus; cerebral abscess; childhood acute leukemia; neutropenia AB A 5-year-old boy with standard-risk B-cell acute lymphoblastic anemia developed fever during induction chemotherapy. The patient had no neurological symptoms. Blood cultures grew Bacillus cereus and neuroimaging studies demonstrated a cerebral abscess. Imaging changes resolved after completion of antibiotics. Bacillus cereus bacteremia is increasingly implicated as the cause of life-threatening infections, including cerebral abscesses, in compromised patients. Positive blood cultures for this organism should prompt neuroimaging and consideration of cerebrospinal fluid sampling, as well as catheter removal. Given the worse outcome with central nervous system involvement, there is a need for increased awareness and early diagnosis, particularly in immunocompromised individuals. C1 [Dabscheck, Gabriel; Ullrich, Nicole J.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Silverman, Lewis; Ullrich, Nicole J.] Dana Farber Canc Inst, Dana Farber Boston Childrens Canc & Blood Disord, Boston, MA 02115 USA. RP Ullrich, NJ (reprint author), Boston Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM nicole.ullrich@childrens.harvard.edu NR 3 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1077-4114 EI 1536-3678 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD OCT PY 2015 VL 37 IS 7 BP 568 EP 569 DI 10.1097/MPH.0000000000000413 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CT1GL UT WOS:000362545900016 PM 26274034 ER PT J AU Christensen, R Singh, JA Wells, GA Tugwell, PS AF Christensen, Robin Singh, Jasvinder A. Wells, George A. Tugwell, Peter S. TI Do "Evidence-Based Recommendations" Need to Reveal the Evidence? Minimal Criteria Supporting an "Evidence Claim" SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID SYSTEMATIC REVIEWS; QUALITY; GUIDELINES; GRADE; STRENGTH C1 [Christensen, Robin] Bispebjerg & Frederiksberg Hosp, Parker Inst, Musculoskeletal Stat Unit, Dept Rheumatol, Copenhagen, Denmark. [Singh, Jasvinder A.] Univ Alabama Birmingham, Med Serv, Birmingham VA Med Ctr, Dept Med,Sch Med, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Wells, George A.] Univ Ottawa, Inst Heart, Ottawa, ON, Canada. [Tugwell, Peter S.] Univ Ottawa, Sch Epidemiol Publ Hlth & Prevent Med, Ottawa, ON, Canada. RP Christensen, R (reprint author), Copenhagen Univ Hosp Frederiksberg, Musculoskeletal Stat Unit, Parker Inst, Nordre Fasanvej 57, DK-2000 Copenhagen F, Denmark. EM robin.christensen@regionh.dk OI Tugwell, Peter/0000-0001-5062-0556 NR 20 TC 2 Z9 2 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2015 VL 42 IS 10 BP 1737 EP 1739 DI 10.3899/jrheum.150846 PG 3 WC Rheumatology SC Rheumatology GA CS7AC UT WOS:000362234900003 PM 26429204 ER PT J AU Maxwell, LJ Wells, GA Simon, LS Conaghan, PG Grosskleg, S Scrivens, K Beaton, DE Bingham, CO Busse, JW Christensen, R Goel, N Juni, P Kaiser, U Lyddiatt, A Mease, PJ Ostelo, RW Phillips, K Sapunar, D Singh, JA Strand, V Taylor, AM Terwee, CB Tugwell, P AF Maxwell, Lara J. Wells, George A. Simon, Lee S. Conaghan, Philip G. Grosskleg, Shawna Scrivens, Kerry Beaton, Dorcas E. Bingham, Clifton O., III Busse, Jason W. Christensen, Robin Goel, Niti Jueni, Peter Kaiser, Ulrike Lyddiatt, Anne Mease, Philip J. Ostelo, Raymond W. Phillips, Kristine Sapunar, Damir Singh, Jasvinder A. Strand, Vibeke Taylor, Ann M. Terwee, Caroline B. Tugwell, Peter TI Current State of Reporting Pain Outcomes in Cochrane Reviews of Chronic Musculoskeletal Pain Conditions and Considerations for an OMERACT Research Agenda SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE PAIN MEASUREMENT; CHRONIC PAIN; OUTCOMES RESEARCH; SYSTEMATIC REVIEW ID UPDATED METHOD GUIDELINES; CLINICAL-TRIALS; IMMPACT RECOMMENDATIONS; SYSTEMATIC REVIEWS; METHODOLOGICAL QUALITY; COSMIN CHECKLIST; FINDINGS TABLES; SETS AB Objective. To assess the current state of reporting of pain outcomes in Cochrane reviews on chronic musculoskeletal painful conditions and to elicit opinions of patients, healthcare practitioners, and methodologists on presenting pain outcomes to patients, clinicians, and policymakers. Methods. We identified all reviews in the Cochrane Library of chronic musculoskeletal pain conditions from Cochrane review groups (Back, Musculoskeletal, and Pain, Palliative, and Supportive Care) that contained a summary of findings (SoF) table. We extracted data on reported pain domains and instruments and conducted a survey and interviews on considerations for SoF tables (e.g., pain domains, presentation of results). Results. Fifty-seven SoF tables in 133 Cochrane reviews were eligible. SoF tables reported pain in 56/57, with all presenting results for pain intensity (20 different outcome instruments), pain interference in 8 SoF tables (5 different outcome instruments), and pain frequency in 1 multiple domain instrument. Other domains like pain quality or pain affect were not reported. From the survey and interviews [response rate 80% (36/45)], we derived 4 themes for a future research agenda: pain domains, considerations for assessing truth, discrimination, and feasibility; clinically important thresholds for responder analyses and presenting results; and establishing hierarchies of outcome instruments. Conclusion. There is a lack of standardization in the domains of pain selected and the manner that pain outcomes are reported in SoF tables, hampering efforts to synthesize evidence. Future research should focus on the themes identified, building partnerships to achieve consensus and develop guidance on best practices for reporting pain outcomes. C1 [Maxwell, Lara J.] Ottawa Hosp Res Inst, Ctr Practice Changing Res, Ottawa, ON, Canada. Univ Ottawa, Sch Epidemiol Publ Hlth & Prevent Med, Ottawa, ON, Canada. Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada. SDG LLC, Cambridge, MA USA. Univ Leeds, Inst Rheumat & Musculoskeletal Med, Leeds, W Yorkshire, England. NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. Univ Ottawa, Ottawa, ON, Canada. Univ Ottawa, Inst Populat Hlth, Ottawa, ON, Canada. Inst Work & Hlth, Toronto, ON, Canada. Johns Hopkins Univ, Dept Med, Div Rheumatol, Baltimore, MD USA. McMaster Univ, Dept Clin Epidemiol & Biostat, Dept Anesthesia, Hamilton, ON, Canada. McMaster Univ, Michael G DeGroote Inst Pain Res & Care, Hamilton, ON, Canada. Bispebjerg & Frederiksberg Hosp, Musculoskeletal Stat Unit, Dept Rheumatol, Parker Inst, Copenhagen, Denmark. Duke Univ, Sch Med, Dept Med, Quintiles Inc,Div Rheumatol, Durham, NC 27706 USA. Univ Bern, Inst Primary Hlth Care BIHAM, Bern, Switzerland. Univ Hosp Carl Gustav Carus, Dresden, Germany. Univ Washington, Seattle, WA 98195 USA. Vrije Univ Amsterdam, Dept Hlth Sci, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, Amsterdam, Netherlands. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Split, Sch Med, Lab Pain Res, Split, Croatia. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama Birmingham, Birmingham, AL USA. Stanford Univ, Sch Med, Div Immunol Rheumatol, Palo Alto, CA 94304 USA. Cardiff Univ, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales. Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Epidemiol & Biostat, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. Univ Ottawa, Fac Med, Dept Med, Ottawa Hosp Res Inst, Ottawa, ON, Canada. Univ Ottawa, Clin Epidemiol Program, Ottawa, ON, Canada. Univ Ottawa, Fac Med, Inst Populat Hlth, Ottawa, ON, Canada. RP Maxwell, LJ (reprint author), Ottawa Hosp Res Inst, Ctr Practice Changing Res, Ottawa, ON, Canada. EM lmaxwell@uottawa.ca RI Sapunar, Damir/E-7247-2010; OI Sapunar, Damir/0000-0002-8352-4402; Busse, Jason/0000-0002-0178-8712; Tugwell, Peter/0000-0001-5062-0556 FU German Ministry of Education and Research [BMBF 01GY1326]; Oak Foundation; Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; US National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [P50 AR060772, U34 AR062891, P30-AR053503]; National Institute of Aging (NIA) [U01 AG018947]; National Cancer Institute (NCI) [U10 CA149950]; Patient Centered Outcomes Research Institute (PCORI) [CE-1304-6631]; Patient-Centered Outcomes Research Institute (PCORI) Pilot Project Program Award [1IP2-PI000737-01]; PCORI Methodology Award [SC14-1402-10818]; Takeda; Savient; Regeneron; Allergan; Astra Zeneca; Biotronik; Biosensors International; Eli Lilly; The Medicines Company; Biosensors; St. Jude Medical; Canadian Institutes of Health Research (CIHR) FX U. Kaiser received a grant from the German Ministry of Education and Research (BMBF 01GY1326); R. Christensen, grants from the Oak Foundation to the Musculoskeletal Statistics Unit at the Parker Institute; J.A. Singh, grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110, US National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) P50 AR060772 and U34 AR062891, National Institute of Aging (NIA) U01 AG018947, National Cancer Institute (NCI) U10 CA149950, the resources and the use of facilities at the VA Medical Center at Birmingham, and research contract CE-1304-6631 from the Patient Centered Outcomes Research Institute (PCORI); C.O. Bingham, in part by grants and awards NIAMS P30-AR053503, a Patient-Centered Outcomes Research Institute (PCORI) Pilot Project Program Award (1IP2-PI000737-01), and a PCORI Methodology Award (SC14-1402-10818); J.A. Singh, research grants from Takeda and Savient and consultant fees from Savient, Takeda, Regeneron and Allergan; member of the American College of Rheumatology's Guidelines Subcommittee of the Quality of Care Committee, and Veterans Affairs Rheumatology Field Advisory Committee; D.E. Beaton, C.O. Bingham, P. Conaghan, L.S. Simon, J.A. Singh, V. Strand, P. Tugwell, and G.A. Wells are members of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 pharmaceutical and clinical research companies, but they do not receive financial remuneration for their activities; P. Juni has received research grants to the institution from Astra Zeneca, Biotronik, Biosensors International, Eli Lilly, and The Medicines Company, and serves as unpaid member of the steering group of trials funded by Astra Zeneca, Biotronik, Biosensors, St. Jude Medical, and The Medicines Company; PT has received honoraria for quality of life consultancy with BMS, chairs data safety monitoring boards for Chelsea and UCB, has mandated for the FDA, co-chairs an industry board of 6 companies (Abbott, BMS, Merck, Roche, Schering Plough, UCB) for a biologics registry of the Ontario Rheumatology Association [Ontario Biologics Research Initiative (arms-length registry that independently collects information)], received a grant from the Canadian Institutes of Health Research (CIHR) matched by funding from these pharmaceutical companies); and receives an honorarium from the CIHR grant. Statements in this report, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of NIAMS, the National Institutes of Health, or the Patient-Centered Outcomes Research Institute, its Board of Governors, or Methodology Committee. NR 25 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2015 VL 42 IS 10 BP 1934 EP 1942 DI 10.3899/jrheum.141423 PG 9 WC Rheumatology SC Rheumatology GA CS7AC UT WOS:000362234900033 PM 26373562 ER PT J AU Beaton, DE Terwee, CB Singh, JA Hawker, GA Patrick, DL Burke, LB Toupin-April, K Tugwell, PS AF Beaton, Dorcas E. Terwee, Caroline B. Singh, Jasvinder A. Hawker, Gillian A. Patrick, Donald L. Burke, Laurie B. Toupin-April, Karine Tugwell, Peter S. TI A Call for Evidence-based Decision Making When Selecting Outcome Measurement Instruments for Summary of Findings Tables in Systematic Reviews: Results from an OMERACT Working Group SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE EVIDENCE BASED; OUTCOME MEASUREMENT; REPRODUCIBILITY OF RESULTS; HEALTH STATUS INDICATORS; SYSTEMATIC REVIEWS ID PATIENT-CENTERED OUTCOMES; METHODOLOGICAL QUALITY; CLINICAL-TRIALS; INTERNATIONAL DELPHI; COSMIN CHECKLIST; FILTER 2.0; OSTEOARTHRITIS; KNEE; PAIN; RESPONSIVENESS AB Objective. Systematic reviews often struggle with how to combine information when more than 1 instrument is used across studies being synthesized. Different techniques have been suggested based on frequency of use in the literature, or on consensus. We explore an approach blending 2 initiatives: OMERACT (Outcome Measurement in Rheumatology) and COSMIN (Consensus On Selection of Measurement Instruments), and investigate the effects of an evidence-based measurement approach on selection of outcomes. Methods. Readings were circulated to attendees registered for a preconference workshop on pain measurement. Three instruments were considered and exercises conducted to engage people in the content and measurement performance of these tools. Consensus was sought that an evidence-based approach could be created for selection of instruments for summary of findings (SoF) tables. Results. The blending of COSMIN and OMERACT approaches led to an evidence-based approach that depended both on a clear definition of target concept and a review of measurement performance of the instrument. Participants emphasized that conceptual clarity and practical considerations should come before measurement property results. Conclusion. Evidence-based approaches can be adopted for selection of instruments for SoF tables. A research agenda was formulated. C1 St Michaels Hosp, Li Ka Shing Knowledge Inst, Musculoskeletal Hlth & Outcomes Res, Toronto, ON M5B 1W8, Canada. [Beaton, Dorcas E.] Inst Work & Hlth, Toronto, ON, Canada. [Beaton, Dorcas E.; Hawker, Gillian A.] Univ Toronto, Toronto, ON, Canada. [Terwee, Caroline B.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Terwee, Caroline B.] EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Hawker, Gillian A.] Womens Coll Hosp, Inst Clin Evaluat Sci, Toronto, ON, Canada. [Patrick, Donald L.] Univ Washington, Seattle Qual Life Grp, Ctr Disabil Policy & Res, Seattle, WA 98195 USA. US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Toupin-April, Karine] Univ Ottawa, Fac Med, Dept Epidemiol & Community Med, Ottawa, ON, Canada. Ottawa Hosp, Res Inst, Fac Med, Dept Med, Ottawa, ON, Canada. Univ Ottawa, Clin Epidemiol Program, Ottawa, ON, Canada. Univ Ottawa, Fac Med, Inst Populat Hlth, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Beaton, DE (reprint author), St Michaels Hosp, 30 Bond St, Toronto, ON M5B 1W8, Canada. EM beatond@smh.ca OI Tugwell, Peter/0000-0001-5062-0556 FU Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; US National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [P50 AR060772, U34 AR062891]; National Institute of Aging [U01 AG018947]; National Cancer Institute [U10 CA149950]; Patient Centered Outcomes Research Institute [CE-1304-6631]; Takeda; Savient; Regeneron; Allergan FX Supported through the OMERACT premeeting conference on pain measurement. JAS is supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110, US National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) P50 AR060772 and U34 AR062891, National Institute of Aging U01 AG018947, National Cancer Institute U10 CA149950, the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama and research contract CE-1304-6631 from the Patient Centered Outcomes Research Institute. JAS has received research grants from Takeda and Savient and consultant fees from Savient, Takeda, Regeneron, and Allergan. JAS is a member of the American College of Rheumatology's Guidelines Subcommittee of the Quality of Care Committee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. JAS, DEB, and PT are members of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies. NR 45 TC 1 Z9 1 U1 2 U2 5 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2015 VL 42 IS 10 BP 1954 EP 1961 DI 10.3899/jrheum.141446 PG 8 WC Rheumatology SC Rheumatology GA CS7AC UT WOS:000362234900036 PM 26373567 ER PT J AU Busse, JW Bartlett, SJ Dougados, M Johnston, BC Guyatt, GH Kirwan, JR Kwoh, K Maxwell, LJ Moore, A Singh, JA Stevens, R Strand, V Suarez-Almazor, ME Tugwell, P Wells, GA AF Busse, Jason W. Bartlett, Susan J. Dougados, Maxime Johnston, Bradley C. Guyatt, Gordon H. Kirwan, John R. Kwoh, Kent Maxwell, Lara J. Moore, Andrew Singh, Jasvinder A. Stevens, Randall Strand, Vibeke Suarez-Almazor, Maria E. Tugwell, Peter Wells, George A. TI Optimal Strategies for Reporting Pain in Clinical Trials and Systematic Reviews: Recommendations from an OMERACT 12 Workshop SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE OMERACT; OUTCOMES; PAIN; CLINICAL TRIALS; VISUAL ANALOG SCALE; SYSTEMATIC REVIEWS ID CHRONIC NEUROPATHIC PAIN; MOTOR CORTEX RTMS; QUALITY-OF-LIFE; IMMPACT RECOMMENDATIONS; OUTCOME MEASURES; RANDOMIZED-TRIAL; EFFECT SIZE; METAANALYSIS; DIFFERENCE; RELIEF AB Objective. Pain is a patient-important outcome, but current reporting in randomized controlled trials and systematic reviews is often suboptimal, impeding clinical interpretation and decision making. Methods. A working group at the 2014 Outcome Measures in Rheumatology (OMERACT 12) was convened to provide guidance for reporting treatment effects regarding pain for individual studies and systematic reviews. Results. For individual trials, authors should report, in addition to mean change, the proportion of patients achieving 1 or more thresholds of improvement from baseline pain (e.g., >=. 20%, >= 30%, >= 50%), achievement of a desirable pain state (e.g., no worse than mild pain), and/or a combination of change and state. Effects on pain should be accompanied by other patient-important outcomes to facilitate interpretation. When pooling data for metaanalysis, authors should consider converting all continuous measures for pain to a 100 mm visual analog scale (VAS) for pain and use the established, minimally important difference (MID) of 10 mm, and the conventionally used, appreciably important differences of 20 mm, 30 mm, and 50 mm, to facilitate interpretation. Effects <= 0.5 units suggest a small or very small effect. To further increase interpretability, the pooled estimate on the VAS should also be transformed to a binary outcome and expressed as a relative risk and risk difference. This transformation can be achieved by calculating the probability of experiencing a treatment effect greater than the MID and the thresholds for appreciably important differences in pain reduction in the control and intervention groups. Conclusion. Presentation of relative effects regarding pain will facilitate interpretation of treatment effects. C1 [Busse, Jason W.] McMaster Univ, Michael G DeGroote Inst Pain Res & Care, Hamilton, ON, Canada. [Busse, Jason W.] McMaster Univ, Dept Anesthesia, Hamilton, ON, Canada. [Busse, Jason W.; Johnston, Bradley C.; Guyatt, Gordon H.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Bartlett, Susan J.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Bartlett, Susan J.] Royal Victoria Hosp, Div Rheumatol, Montreal, PQ H3A 1A1, Canada. [Bartlett, Susan J.] Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada. [Dougados, Maxime] Paris Descartes Univ, Cochin Hosp, APHP,PRES Sorbonne Paris Cite, Rheumatol Dept,INSERM,U1153,Clin Epidemiol & Bios, Paris, France. [Johnston, Bradley C.] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. [Johnston, Bradley C.] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Johnston, Bradley C.] Univ Toronto, Hosp Sick Children, Dept Anesthesia & Pain Med, Toronto, ON M5G 1X8, Canada. [Kirwan, John R.] Univ Bristol, Acad Rheumatol Unit, Bristol Royal Infirm, Bristol, Avon, England. [Kwoh, Kent] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, Kent] Vet Affairs VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Maxwell, Lara J.] Univ Ottawa, Inst Populat Hlth, Ottawa, ON, Canada. [Moore, Andrew] Univ Oxford, Nuffield Div Anaesthet, Pain Res, Oxford, England. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Stevens, Randall] Celgene Corp, Inflammat & Immunol Clin Res, Summit, NJ USA. [Stevens, Randall] Rutgers State Univ, Dept Med, Div Rheumatol, New Brunswick, NJ 08903 USA. [Strand, Vibeke] Stanford Univ, Div Immunol Rheumatol, Palo Alto, CA 94304 USA. [Suarez-Almazor, Maria E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Tugwell, Peter] Univ Ottawa, Fac Med, Dept Med, Inst Populat Hlth, Ottawa, ON, Canada. [Tugwell, Peter] Ottawa Hosp, Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Tugwell, Peter; Wells, George A.] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Busse, JW (reprint author), McMaster Univ, Michael G DeGroote Sch Med, Dept Anesthesia, Hamilton, ON, Canada. EM bussejw@mcmaster.ca RI DOUGADOS, MAXIME/P-5287-2016; OI Busse, Jason/0000-0002-0178-8712; Bartlett, Susan/0000-0001-9755-2490; Tugwell, Peter/0000-0001-5062-0556 FU US Agency for Health Quality and Research Center for Education and Research on Therapeutics [U19 HS021110]; National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [P50 AR060772, U34 AR062891]; National Institute of Aging [U01 AG018947]; National Cancer Institute [U10 CA149950]; Patient-Centered Outcomes Research Institute [CE-1304-6631]; NIAMS [K24AR053593] FX JAS is supported by grants from the US Agency for Health Quality and Research Center for Education and Research on Therapeutics U19 HS021110, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) P50 AR060772 and U34 AR062891, National Institute of Aging U01 AG018947, National Cancer Institute U10 CA149950, the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama, USA, and research contract CE-1304-6631 from the Patient-Centered Outcomes Research Institute. MSA is the recipient of a K24 award from NIAMS (K24AR053593) NR 49 TC 8 Z9 8 U1 1 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2015 VL 42 IS 10 BP 1962 EP 1970 DI 10.3899/jrheum.141440 PG 9 WC Rheumatology SC Rheumatology GA CS7AC UT WOS:000362234900037 PM 25979719 ER PT J AU Christensen, R Maxwell, LJ Juni, P Tovey, D Williamson, PR Boers, M Goel, N Buchbinder, R March, L Terwee, CB Singh, JA Tugwell, P AF Christensen, Robin Maxwell, Lara J. Jueni, Peter Tovey, David Williamson, Paula R. Boers, Maarten Goel, Niti Buchbinder, Rachelle March, Lyn Terwee, Caroline B. Singh, Jasvinder A. Tugwell, Peter TI Consensus on the Need for a Hierarchical List of Patient-reported Pain Outcomes for Metaanalyses of Knee Osteoarthritis Trials: An OMERACT Objective SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE OMERACT; METAANALYSIS; OSTEOARTHRITIS; PAIN; PATIENT OUTCOME ASSESSMENT; COCHRANE COLLABORATION ID CLINICAL-TRIALS; SYSTEMATIC REVIEWS; RECOMMENDATIONS; HIP; GUIDELINES; MANAGEMENT; PROTOCOLS; COSMIN AB Objective. Although protocol registration for systematic reviews is still not mandatory, reviewers should be strongly encouraged to register the protocol to identify the methodological approach, including all outcomes of interest. This will minimize the likelihood of biased decisions in reviews, such as selective outcome reporting. A group of international experts convened to address issues regarding the need to develop hierarchical lists of outcome measurement instruments for a particular outcome for metaanalyses. Methods. Multiple outcome measurement instruments exist to measure the same outcome. Metaanalysis of knee osteoarthritis (OA) trials, and the assessment of pain as an outcome, was used as an exemplar to assess how Outcome Measures in Rheumatology (OMERACT), the Cochrane Collaboration, and other international initiatives might contribute in this area. The meeting began with formal presentations of background topics, empirical evidence from the literature, and a brief introduction to 2 existing hierarchical lists of pain outcome measurement instruments recommended for metaanalyses of knee OA trials. Results. After discussions, most participants agreed that there is a need to develop a methodology for generation of hierarchical lists of outcome measurement instruments to guide metaanalyses. Tools that could be used to steer development of such a prioritized list are the COSMIN checklist (COnsensus-based Standards for the selection of health status Measurement Instruments) and the OMERACT Filter 2.0. Conclusion. We list meta-epidemiological research agenda items that address the frequency of reported outcomes in trials, as well as methodologies to assess the best measurement properties (i.e., truth, discrimination, and feasibility). C1 Copenhagen Univ Hosp, Musculoskeletal Stat Unit, Parker Inst, Dept Rheumatol, Bispebjerg, Denmark. Copenhagen Univ Hosp, Musculoskeletal Stat Unit, Parker Inst, Dept Rheumatol, Frederiksberg, Denmark. Univ Ottawa, Inst Populat Hlth, Ottawa, ON, Canada. Univ Ottawa, Dept Med, Ottawa, ON, Canada. Univ Bern, Inst Social & Prevent Med, Dept Clin Res, Bern, Switzerland. Univ Bern, Clin Trials Unit Bern, Dept Clin Res, Bern, Switzerland. Cochrane Collaborat, London, England. Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Rheumatol, Amsterdam, Netherlands. Quintiles Inc, Durham, NC USA. Duke Univ, Sch Med, Dept Med, Div Rheumatol, Durham, NC 27706 USA. Monash Univ, Dept Epidemiol & Prevent Med, Sch Publ Hlth & Prevent Med, Melbourne, Vic 3004, Australia. Cabrini Hlth, Monash Dept Clin Epidemiol, Melbourne, Vic, Australia. Univ Sydney, Northern Clin Sch, Inst Bone & Joint Res, Dept Rheumatol, Sydney, NSW 2006, Australia. Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Epidemiol & Biostat, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. Birmingham Vet Affairs VA Med Ctr, Birmingham, AL USA. Univ Alabama Birmingham, Birmingham, AL USA. RP Christensen, R (reprint author), Copenhagen Univ Hosp Frederiksberg, Musculoskeletal Stat Unit, Parker Inst, Nordre Fasanvej 57, DK-2000 Copenhagen F, Denmark. EM robin.christensen@regionh.dk OI Tugwell, Peter/0000-0001-5062-0556 FU Oak Foundation; Australian National Health and Research Council Practitioner Fellowship; Medical Research Council; European Commission; US Agency for Health Quality and Research Center for Education and Research on Therapeutics [U19 HS021110,]; US National Institute of Arthritis and Musculoskeletal and Skin Diseases [P50 AR060772, U34 AR062891]; US National Institute on Aging [U01 AG018947]; US National Cancer Institute [U10 CA149950]; Patient-Centered Outcomes Research Institute [CE-1304-6631] FX RC is supported by unrestricted grants from The Oak Foundation; RB is supported in part by an Australian National Health and Research Council Practitioner Fellowship; PRW is supported by grants for the COMET Initiative from the Medical Research Council and the European Commission; JAS is supported by grants from the US Agency for Health Quality and Research Center for Education and Research on Therapeutics U19 HS021110, US National Institute of Arthritis and Musculoskeletal and Skin Diseases P50 AR060772 and U34 AR062891, US National Institute on Aging U01 AG018947, US National Cancer Institute U10 CA149950, the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama, USA, and research contract CE-1304-6631 from theA Patient-Centered Outcomes Research Institute. NR 34 TC 1 Z9 1 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2015 VL 42 IS 10 BP 1971 EP 1975 DI 10.3899/jrheum.141384 PG 5 WC Rheumatology SC Rheumatology GA CS7AC UT WOS:000362234900038 PM 25934823 ER PT J AU Sloan, VS Grosskleg, S Pohl, C Wells, GA Singh, JA AF Sloan, Victor S. Grosskleg, Shawna Pohl, Christoph Wells, George A. Singh, Jasvinder A. TI The OMERACT First-time Participant ("Newbie") Program: Initial Assessment and Lessons Learned SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE OMERACT; FILTER; OUTCOME MEASURES; TRAINING SESSION; PARTICIPANT EXPERIENCE ID OUTCOME MEASUREMENT SETS; NOMINAL GROUP TECHNIQUE; CLINICAL-TRIALS; FILTER 2.0; RHEUMATOLOGY AB Objective. To describe the experience of a first-time participant ("newbie") training program at the Outcome Measures in Rheumatology 12 meeting in 2014. Methods. We conducted newbie sessions at OMERACT 12, including a 2-hour introductory session on Day 1, followed by 1-h evening followup sessions on days 1-4 of OMERACT 12. Pre- and postmeeting surveys assessed participants' level of comfort with the principles of the OMERACT Filters 1.0 (truth, discrimination, feasibility), and Filter 2.0 (the essential tools for OMERACT methodology), the different types of OMERACT sessions, and whether participants felt welcome. Results. In all, 25 new attendees participated in the introductory session and 10-16 attended followup sessions. Fewer participants reported being somewhat or extremely uncomfortable with the meeting, comparing Day 1 (preintroductory session) to days 1-4 (post): (1) with different OMERACT sessions: 56% (pre) versus 6%, 0%, 8%, and 6% (post days 1-4, respectively); and (2) with principles of the OMERACT filter, 64% (pre) versus 7%, 0%, 8%, and 0% (post), respectively. Most reported feeling welcome (100%) and that they were able to contribute substantively to breakout sessions (87%) on Day 1 evening; results were sustained on days 2-4. Conclusion. First-time participant training sessions increased the comfort level of the participants with the OMERACT meeting structure and filter, and increased the ability of the new attendees to feel they could contribute to the OMERACT process. C1 [Sloan, Victor S.] Rutgers Robert Wood Johnson Med Sch, Med, New Brunswick, NJ USA. [Sloan, Victor S.] UCB Biosci Inc, Raleigh, NC USA. [Grosskleg, Shawna] Univ Ottawa, OMERACT, Ottawa, ON, Canada. [Pohl, Christoph] Charite, Dept Internal Med Rheumatol Clin Immunol Osteol P, Schlosspark Klin, Teaching Hosp, D-13353 Berlin, Germany. [Wells, George A.] Ottawa Heart Inst, Biostat, Ottawa, ON, Canada. [Wells, George A.] Univ Ottawa, Ottawa, ON, Canada. [Singh, Jasvinder A.] Univ Alabama Birmingham, Med & Epidemiol, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com NR 8 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2015 VL 42 IS 10 BP 1976 EP 1981 DI 10.3899/jrheum.141200 PG 6 WC Rheumatology SC Rheumatology GA CS7AC UT WOS:000362234900039 PM 26034159 ER PT J AU Buxton, D AF Buxton, David TI Child and Adolescent Psychiatry and Palliative Care SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 [Buxton, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Buxton, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Buxton, David] Butler Hosp, Providence, RI 02906 USA. [Buxton, David] Brown Univ, Providence, RI 02912 USA. RP Buxton, D (reprint author), 7101 Janke Rd, Richmond, VA 23225 USA. EM dbuxton80@yahoo.com NR 4 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2015 VL 54 IS 10 BP 791 EP 792 DI 10.1016/j.jaac.2015.05.017 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CS4PA UT WOS:000362056800003 PM 26407485 ER PT J AU Guzman, J Kessler, RC Squicciarini, AM George, M Baer, L Canenguez, KM Abel, MR McCarthy, A Jellinek, MS Murphy, JM AF Guzman, Javier Kessler, Ronald C. Squicciarini, Ana Maria George, Myriam Baer, Lee Canenguez, Katia M. Abel, Madelaine R. McCarthy, Alyssa Jellinek, Michael S. Murphy, J. Michael TI Evidence for the Effectiveness of a National School-Based Mental Health Program in Chile SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE children's mental health; school-based interventions; behavior problems; academic achievement ID PEDIATRIC SYMPTOM CHECKLIST; PSYCHOSOCIAL DYSFUNCTION; BEHAVIORAL-PROBLEMS; INCOME COUNTRIES; CHILDREN; INTERVENTIONS; STUDENTS; TRIAL; SCHOOLCHILDREN; ACHIEVEMENT AB Objective: Skills for Life (SFL) is the largest school-based mental health program in the world, screening and providing services to more than 1,000,000 students in Chile over the past decade. This is the first external evaluation of the program. Method: Of the 8,372 primary schools in Chile in 2010 that received public funding, one-fifth (1,637) elected to participate in SFL. Each year, all first- and third-grade students in these schools are screened with validated teacher- and parent-completed measures of psychosocial functioning (the Teacher Observation of Classroom Adaptation Re-Revised [TOCA-RE.] and the Pediatric Symptom Checklist Chile [PSC-CL]). Students identified as being at risk on the TOCA-RR in first grade are referred to a standardized 10-session preventive intervention in second grade. This article explores the relationships between workshop participation and changes in TOCA-RR and PSC-CL scores, attendance, and promotion from third to fourth grades. Results: In all, 16.4% of students were identified as being at-risk on the. TOCA-RR. Statistically significant 'relationships were found between the number of workshop sessions attended and improvements in behavioral and academic outcomes after controlling for nonrandom selection into exposure and loss to follow-up. Effect sizes for the difference between attending most (7-10) versus fewer (0-6) sessions ranged from 0.08 to 0.16 standard deviations. Conclusion: This study provides empirical evidence that a large-scale mental health intervention early in schooling is significantly associated with improved behavioral and academic outcomes. Future research is needed to implement more rigorous experimental evaluation of the program, to examine longer-term effects, and to investigate possible predictors of heterogeneity of treatment response. C1 [Guzman, Javier; Squicciarini, Ana Maria] Junta Nacl Auxilio Escolar & Becas JUNAEB Chile, Skills Life Program, Santiago, Chile. [Guzman, Javier] Univ Desarrollo, Santiago, Chile. [Guzman, Javier] Boston Univ, Sch Educ, Boston, MA 02215 USA. [Baer, Lee; Canenguez, Katia M.; Abel, Madelaine R.; Murphy, J. Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kessler, Ronald C.; Baer, Lee; Canenguez, Katia M.; Jellinek, Michael S.; Murphy, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. [George, Myriam] Univ Chile, Santiago, Chile. [McCarthy, Alyssa] Rutgers State Univ, New Brunswick, NJ 08903 USA. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Yawkey 6A, Boston, MA 02114 USA. EM mmurphy6@partners.org RI Guzman, Javier /E-8170-2016 OI Guzman, Javier /0000-0002-8194-039X FU Chilean government; JUNAEB branch of the Chilean Ministry of Education; Fuss Family Fund FX All of the Chilean authors received salary contributions from either the Chilean government for running the mental health promotion program and/or gathering data about it, or from an evaluation contract with the Chilean government-for data analyses. All US authors except Drs. Kessler and Jellinek received salary or consultation support for secondary data analysis or report writing described in this report. The mental health promotion program and all related data collection are funded through the annual budget of the JUNAEB branch of the Chilean Ministry of Education, as is the basic data analysis. A generous Fuss Family Fund grant to Massachusetts General Hospital made the current data analysis and paper writing possible (salary support for Drs. Murphy and Baer, Ms. McCarthy, and Ms. Abel). NR 40 TC 3 Z9 3 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2015 VL 54 IS 10 BP 799 EP 807 DI 10.1016/j.jaac.2015.07.005 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CS4PA UT WOS:000362056800007 PM 26407489 ER PT J AU Chen, J AF Chen, Juliana TI Case Formulation With Children and Adolescents. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Chen, Juliana] Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, Boston, MA 02114 USA. [Chen, Juliana] McLean Child & Adolescent Psychiat Residency Trai, Boston, MA USA. RP Chen, J (reprint author), Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, Boston, MA 02114 USA. EM jchen21@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2015 VL 54 IS 10 BP 870 EP 871 DI 10.1016/j.jaac.2015.08.002 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CS4PA UT WOS:000362056800017 ER PT J AU Flynn, A Li, Q Panagia, M Abdelbaky, A MacNabb, M Samir, A Cypess, AM Weyman, AE Tawakol, A Scherrer-Crosbie, M AF Flynn, Aidan Li, Qian Panagia, Marcello Abdelbaky, Amr MacNabb, Megan Samir, Anthony Cypess, Aaron M. Weyman, Arthur E. Tawakol, Ahmed Scherrer-Crosbie, Marielle TI Contrast-Enhanced Ultrasound: A Novel Noninvasive, Nonionizing Method for the Detection of Brown Adipose Tissue in Humans SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Brown adipose tissue; Contrast-enhanced ultrasound; Imaging; Positron emission tomography; Activation ID BLOOD-FLOW; NONSHIVERING THERMOGENESIS; CORONARY STENOSIS; ADULT HUMANS; REAL-TIME; COLD; ECHOCARDIOGRAPHY; OBESITY; MICE; RAT AB Background: Brown adipose tissue (BAT) consumes glucose when it is activated by cold exposure, allowing its detection in humans by 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT). The investigators recently described a novel noninvasive and nonionizing imaging method to assess BAT in mice using contrast-enhanced ultrasound (CEUS). Here, they report the application of this method in healthy humans. Methods: Thirteen healthy volunteers were recruited. CEUS was performed before and after cold exposure in all subjects using a continuous intravenous infusion of perflutren gas-filled lipid microbubbles and triggered imaging of the supraclavicular space. The first five subjects received microbubbles at a lower infusion rate than the subsequent eight subjects and were analyzed as a separate group. Blood flow was estimated as the product of the plateau (A) and the slope (beta) of microbubble replenishment curves. All underwent F-18-FDG PET/CT after cold exposure. Results: An increase in the acoustic signal was noted in the supraclavicular adipose tissue area with increasing triggering intervals in all subjects, demonstrating the presence of blood flow. The area imaged by CEUS colocalized with BAT, as detected by F-18-FDGPET/CT. In a cohort of eight subjects with an optimized CEUS protocol, CEUS-derived BAT blood flow increased with cold exposure compared with basal BAT blood flow in warm conditions (median A beta = 3.3 AU/s [interquartile range, 0.5-5.7AU/s] vs 1.25AU/s [interquartile range, 0.5-2.6 AU/s]; P = .02). Of these eight subjects, five had greater than twofold increases in blood flow after cold exposure; these responders had higher BAT activity measured by F-18-FDG PET/CT (median maximal standardized uptake value, 2.25 [interquartile range, 1.53-4.57] vs 0.51 [interquartile range, 0.47-0.73]; P = .02). Conclusions: The present study demonstrates the feasibility of using CEUS as a noninvasive, nonionizing imaging modality in estimating BAT blood flow in young, healthy humans. CEUS may be a useful and scalable tool in the assessment of BAT and BAT-targeted therapies. C1 [Flynn, Aidan; Panagia, Marcello; Weyman, Arthur E.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Li, Qian; Samir, Anthony] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Abdelbaky, Amr; MacNabb, Megan; Tawakol, Ahmed] Massachusetts Gen Hosp, Dept Nucl Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Cypess, Aaron M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. [Cypess, Aaron M.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 254,55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com FU National Institutes of Health (Bethesda, MD) [R21-DK092909, K23-DK081604]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) FX This work was supported by grants R21-DK092909 (M.S.-C.) and K23-DK081604 (A.M.C.) from the National Institutes of Health (Bethesda, MD); and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). NR 32 TC 7 Z9 7 U1 1 U2 7 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 OCT PY 2015 VL 28 IS 10 BP 1247 EP 1254 DI 10.1016/j.echo.2015.06.014 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CS9KT UT WOS:000362410700015 PM 26255029 ER PT J AU Deveau, AP Forrester, AM Coombs, AJ Wagner, GS Grabher, C Chute, IC Leger, D Mingay, M Alexe, G Rajan, V Liwski, R Hirst, M Steigmaier, K Lewis, SM Look, AT Berman, JN AF Deveau, A. P. Forrester, A. M. Coombs, A. J. Wagner, G. S. Grabher, C. Chute, I. C. Leger, D. Mingay, M. Alexe, G. Rajan, V. Liwski, R. Hirst, M. Steigmaier, K. Lewis, S. M. Look, A. T. Berman, J. N. TI Epigenetic therapy restores normal hematopoiesis in a zebrafish model of NUP98-HOXA9-induced myeloid disease SO LEUKEMIA LA English DT Article ID TRANS-RETINOIC ACID; STEM-CELL; GENE-EXPRESSION; VALPROIC ACID; MYELODYSPLASTIC SYNDROMES; PROMYELOCYTIC LEUKEMIA; HISTONE DEACETYLASE; HDAC INHIBITORS; HOXA9; DIFFERENTIATION AB Acute myeloid leukemia (AML) occurs when multiple genetic aberrations alter white blood cell development, leading to hyperproliferation and arrest of cell differentiation. Pertinent animal models link in vitro studies with the use of new agents in clinical trials. We generated a transgenic zebrafish expressing human NUP98-HOXA9 (NHA9), a fusion oncogene found in high-risk AML. Embryos developed a preleukemic state with anemia and myeloid cell expansion, and adult fish developed a myeloproliferative neoplasm (MPN). We leveraged this model to show that NHA9 increases the number of hematopoietic stem cells, and that oncogenic function of NHA9 depends on downstream activation of meis1, the PTGS/COX pathway and genome hypermethylation through the DNA methyltransferase, dnmt1. We restored normal hematopoiesis in NHA9 embryos with knockdown of meis1 or dnmt1, as well as pharmacologic treatment with DNA (cytosine-5)-methyltransferase (DNMT) inhibitors or cyclo-oxygenase (COX) inhibitors. DNMT inhibitors reduced genome methylation to near normal levels. Strikingly, we discovered synergy when we combined sub-monotherapeutic doses of a histone deacetylase inhibitor plus either a DNMT inhibitor or COX inhibitor to block the effects of NHA9 on zebrafish blood development. Our work proposes novel drug targets in NHA9-induced myeloid disease, and suggests rational therapies by combining minimal doses of known bioactive compounds. C1 [Deveau, A. P.; Forrester, A. M.; Rajan, V.; Lewis, S. M.; Berman, J. N.] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS B3H 4R2, Canada. [Deveau, A. P.; Forrester, A. M.; Coombs, A. J.; Wagner, G. S.; Rajan, V.; Berman, J. N.] IWK Hlth Ctr, Dept Pediat, Halifax, NS, Canada. [Coombs, A. J.; Wagner, G. S.] Dalhousie Univ, Dept Marine Biol, Halifax, NS B3H 4R2, Canada. [Grabher, C.; Alexe, G.; Steigmaier, K.; Look, A. T.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Grabher, C.] Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76021 Karlsruhe, Germany. [Chute, I. C.; Leger, D.; Lewis, S. M.] Univ New Brunswick, Dept Biol, St John, NB E2L 4L5, Canada. [Mingay, M.; Hirst, M.] Univ British Columbia, Ctr High Throughput Biol, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada. [Alexe, G.; Steigmaier, K.] Harvard Univ, Sch Med, Boston, MA USA. [Liwski, R.] Queen Elizabeth 2 Hlth Sci Ctr, Dept Pathol, Halifax, NS, Canada. [Liwski, R.; Berman, J. N.] Dalhousie Univ, Dept Pathol, Halifax, NS B3H 4R2, Canada. [Hirst, M.] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. [Lewis, S. M.] Univ Moncton, Dept Chem & Biochem, Moncton, NB E1A 3E9, Canada. [Lewis, S. M.] Atlantic Canc Res Inst, Moncton, NB, Canada. [Berman, J. N.] Dalhousie Univ, Dept Pediat, Halifax, NS B3H 4R2, Canada. RP Berman, JN (reprint author), Dalhousie Univ, Life Sci Res Inst, Dept Pediat, Berman Lab N103, 1348 Summer St, Halifax, NS B3H 4R2, Canada. EM jason.berman@iwk.nshealth.ca RI Lewis, Stephen/E-5533-2010; Hirst, Martin/B-7684-2016 OI Lewis, Stephen/0000-0001-9537-5822; FU Canadian Institutes of Health Research /Nova Scotia Health Research Foundation Regional Partnership Program Grant MED-Matching [2011-7509, 243778]; Cancer Research Training Program - Terry Fox Strategic Health Research Training Program in Cancer Research by the Beatrice Hunter Cancer Research Institute; Canadian Institutes of Health Research Banting and Best Graduate Student Award; MeDIP-seq Program Project Grant - Terry Fox Foundation [TFF-122869]; Cancer Care Nova Scotia Peggy Davison Clinician Scientist Award FX We thank Angela Young, Jessica Hill and Emma Cummings for zebrafish care and maintenance; Jocelyn Jaques for administrative support. This work is supported by a Canadian Institutes of Health Research /Nova Scotia Health Research Foundation Regional Partnership Program Grant MED-Matching 2011-7509 (CIHR#.243778). APD is funded by The Cancer Research Training Program, supported by The Terry Fox Strategic Health Research Training Program in Cancer Research by the Beatrice Hunter Cancer Research Institute. AMF is funded by a Canadian Institutes of Health Research Banting and Best Graduate Student Award. The MeDIP work is supported by the MeDIP-seq Program Project Grant funded by Terry Fox Foundation (TFF-122869) to MH. JNB is supported by a Cancer Care Nova Scotia Peggy Davison Clinician Scientist Award. NR 61 TC 10 Z9 10 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD OCT PY 2015 VL 29 IS 10 BP 2086 EP 2097 DI 10.1038/leu.2015.126 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA CT0ST UT WOS:000362507600015 PM 26017032 ER PT J AU Walter, RB Othus, M Paietta, EM Racevskis, J Fernandez, HF Lee, JW Sun, Z Tallman, MS Patel, J Gonen, M Abdel-Wahab, O Levine, RL Estey, EH AF Walter, R. B. Othus, M. Paietta, E. M. Racevskis, J. Fernandez, H. F. Lee, J-W Sun, Z. Tallman, M. S. Patel, J. Goenen, M. Abdel-Wahab, O. Levine, R. L. Estey, E. H. TI Effect of genetic profiling on prediction of therapeutic resistance and survival in adult acute myeloid leukemia SO LEUKEMIA LA English DT Letter ID RESIDUAL DISEASE DETECTION; PROGNOSTIC RELEVANCE; INDUCTION THERAPY; CLEARANCE; IMPACT C1 [Walter, R. B.; Estey, E. H.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Walter, R. B.; Estey, E. H.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. [Walter, R. B.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Othus, M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Paietta, E. M.; Racevskis, J.] Montefiore Med Ctr, Albert Einstein Coll Med, North Div, Dept Oncol, Bronx, NY 10467 USA. [Fernandez, H. F.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Blood & Marrow Transplant, Tampa, FL 33682 USA. [Lee, J-W; Sun, Z.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Tallman, M. S.; Abdel-Wahab, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA. [Patel, J.; Abdel-Wahab, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Goenen, M.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Walter, RB (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. EM rwalter@fredhutch.org RI Walter, Roland/C-1064-2008 OI Walter, Roland/0000-0002-9268-3341 FU NCI NIH HHS [U10 CA180827, CA180791, CA180867, CA189859, R01 CA090998, R21-CA182010, U10 CA017145, U10 CA021115, U10 CA073590, U10 CA180791, CA180820, CA180794, R01 CA173636, R01-CA090998-09, R21 CA182010, U10 CA014958, U10 CA023318, U10 CA066636, U10 CA180794, U10 CA180819, U10 CA180820, U24 CA196172] NR 14 TC 12 Z9 12 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD OCT PY 2015 VL 29 IS 10 BP 2104 EP 2107 DI 10.1038/leu.2015.76 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA CT0ST UT WOS:000362507600018 PM 25772026 ER PT J AU Rao, SK Kimball, AB Torchiana, DF AF Rao, Sandhya K. Kimball, Alexa B. Torchiana, David F. TI Teachable Action for Leaders Committed to Improving Physician Work Life: Continuing Education SO MAYO CLINIC PROCEEDINGS LA English DT Letter ID SATISFACTION; PREDICTORS C1 [Rao, Sandhya K.; Kimball, Alexa B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Torchiana, David F.] Harvard Univ, Sch Med, Partners Healthcare, Boston, MA USA. RP Rao, SK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2015 VL 90 IS 10 BP 1455 EP 1456 DI 10.1016/j.mayocp.2015.07.020 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CS9YN UT WOS:000362450100023 PM 26434970 ER PT J AU Steensma, DP Shampo, MA Kyle, RA AF Steensma, David P. Shampo, Marc A. Kyle, Robert A. TI Ernesto "Che" Guevara de la Serna: Argentinian Marxist Revolutionary SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, Dept Med Oncol, 450 Brookline Ave,D2037, Boston, MA 02215 USA. EM david_steensma@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2015 VL 90 IS 10 BP E111 EP E112 DI 10.1016/j.mayocp.2015.07.027 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CS9YN UT WOS:000362450100002 PM 26434975 ER PT J AU Wang, G Kalra, M Murugan, V Xi, Y Gjesteby, L Getzin, M Yang, QS Cong, WX Vannier, M AF Wang, Ge Kalra, Mannudeep Murugan, Venkatesh Xi, Yan Gjesteby, Lars Getzin, Matthew Yang, Qingsong Cong, Wenxiang Vannier, Michael TI Vision 20/20: Simultaneous CT-MRI - Next chapter of multimodality imaging SO MEDICAL PHYSICS LA English DT Article DE multimodality imaging; simultaneous CT-MRI; interior tomography; omnitomography ID X-RAY/MR SYSTEM; INTERIOR TOMOGRAPHY; COMPUTED-TOMOGRAPHY; PERFUSION PARAMETERS; INHOMOGENEOUS FIELDS; CORONARY-ARTERIES; MAGNETIC-FIELDS; GRADIENT COILS; BREAST-CANCER; LINAC SYSTEM AB Multimodality imaging systems such as positron emission tomography-computed tomography (PET-CT) and MRI-PET are widely available, but a simultaneous CT-MRI instrument has not been developed. Synergies between independent modalities, e.g., CT, MRI, and PET/SPECT can be realized with image registration, but such postprocessing suffers from registration errors that can be avoided with synchronized data acquisition. The clinical potential of simultaneous CT-MRI is significant, especially in cardiovascular and oncologic applications where studies of the vulnerable plaque, response to cancer therapy, and kinetic and dynamic mechanisms of targeted agents are limited by current imaging technologies. The rationale, feasibility, and realization of simultaneous CT-MRI are described in this perspective paper. The enabling technologies include interior tomography, unique gantry designs, open magnet and RF sequences, and source and detector adaptation. Based on the experience with PET-CT, PET-MRI, and MRI-LINAC instrumentation where hardware innovation and performance optimization were instrumental to construct commercial systems, the authors provide top-level concepts for simultaneous CT-MRI to meet clinical requirements and new challenges. Simultaneous CT-MRI fills a major gap of modality coupling and represents a key step toward the so-called "omnitomography" defined as the integration of all relevant imaging modalities for systems biology and precision medicine. (C) 2015 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License. C1 [Wang, Ge; Xi, Yan; Gjesteby, Lars; Getzin, Matthew; Yang, Qingsong; Cong, Wenxiang] Rensselaer Polytech Inst, Biomed Imaging Ctr Cluster, Troy, NY 12180 USA. [Kalra, Mannudeep; Murugan, Venkatesh] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Vannier, Michael] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. RP Wang, G (reprint author), Rensselaer Polytech Inst, Biomed Imaging Ctr Cluster, Troy, NY 12180 USA. EM wangg6@rpi.edu NR 80 TC 4 Z9 5 U1 3 U2 18 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2015 VL 42 IS 10 BP 5879 EP 5889 DI 10.1118/1.4929559 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT1OY UT WOS:000362570100031 PM 26429262 ER PT J AU Lin, YT Paganetti, H McMahon, SJ Schuemann, J AF Lin, Yuting Paganetti, Harald McMahon, Stephen J. Schuemann, Jan TI Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons SO MEDICAL PHYSICS LA English DT Article DE gold nanoparticles; vasculature dose enhancement; radiotherapy; proton therapy; Monte Carlo simulation ID ENHANCED RADIOTHERAPY; DISRUPTING AGENTS; TUMOR RESPONSE; RADIATION; THERAPY; APOPTOSIS; MICE; RADIOSENSITIVITY; HIF-1 AB Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 mu m from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photon beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 mu m) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. Conclusions: GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor. (C) 2015 American Association of Physicists in Medicine. C1 [Lin, Yuting; Paganetti, Harald; McMahon, Stephen J.; Schuemann, Jan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lin, Yuting; Paganetti, Harald; McMahon, Stephen J.; Schuemann, Jan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [McMahon, Stephen J.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7AE, Antrim, North Ireland. RP Lin, YT (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM yuting1188@gmail.com FU Medical Physics Residency Program at Harvard Medical School; NIH/NCI Grant [R01CA187003]; Marie Curie International Outgoing Fellowship from the European Community's Seventh Framework Programme FP7-PEOPLE-2013-IOF [623630] FX We thank the Medical Physics Residency Program at Harvard Medical School for generous support to Yuting Lin. We thank Dr. Kathryn Held for providing valuable discussion for this project. This work was partially supported by NIH/NCI Grant No. R01CA187003. We thank Jonathan Jackson and Tao Song of the Enterprise Research Infrastructure and Services (ERIS) group at Partners Healthcare for their in-depth support and smooth computing cluster operations, upgrades, and fixes. S.J.M. is currently supported by a Marie Curie International Outgoing Fellowship from the European Community's Seventh Framework Programme FP7-PEOPLE-2013-IOF (Project No. 623630). NR 38 TC 2 Z9 2 U1 5 U2 18 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2015 VL 42 IS 10 BP 5890 EP 5902 DI 10.1118/1.4929975 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT1OY UT WOS:000362570100032 PM 26429263 ER PT J AU Solomon, AJ Klein, EP Corboy, JR Bernat, JL AF Solomon, Andrew J. Klein, Eran P. Corboy, John R. Bernat, James L. TI Patient perspectives on physician conflict of interest in industry-sponsored clinical trials for multiple sclerosis therapeutics SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Multiple sclerosis; clinical trials; conflict of interest; professional conduct and ethics; industry-sponsored clinical trials ID POTENTIAL RESEARCH PARTICIPANTS; FINANCIAL INTERESTS; VIEWS; DISCLOSURE; GUIDELINES; ATTITUDES AB Background: Pharmaceutical industry financial support of physicians, physician practices, and academic departments involved in multicenter industry-sponsored clinical trials of novel therapeutic agents is a relatively new and infrequently acknowledged source of potential physician conflict of interest. Detailed disclosure of these relationships to study participants is not uniformly a part of informed consent and documentation practices. Objective: To understand attitudes of patients with multiple sclerosis concerning disclosure of potential physician-industry conflicts of interest created by clinical trials and how such disclosures may influence study participation Methods: An anonymous online instrument was developed. Results: 597 people with multiple sclerosis participated in the study. The study found that detailed disclosure of conflicts of interest is important to potential participants in industry-sponsored clinical trials for multiple sclerosis therapies and that the presence of these conflicts of interest may influence patients' decisions to participate in these studies. Conclusions: Findings from this study support a call for uniform guidelines regarding disclosure of physician-industry relationships to prospective research participants for industry-sponsored clinical trials. C1 [Solomon, Andrew J.] Univ Vermont, Coll Med, Burlington, VT 05401 USA. [Klein, Eran P.] Oregon Hlth & Sci Univ, Portland, OR USA. [Klein, Eran P.] Portland VA Med Ctr, Portland, VA USA. [Klein, Eran P.] Univ Washington, Dept Philosophy, Seattle, WA 98195 USA. [Corboy, John R.] Univ Colorado, Sch Med, Boulder, CO 80309 USA. [Corboy, John R.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Bernat, James L.] Dartmouth Hitchcock Med Ctr, Dept Neurol, Lebanon, NH USA. RP Solomon, AJ (reprint author), Univ Vermont, Coll Med, 1 South Prospect St,Arnold 2, Burlington, VT 05401 USA. EM andrew.solomon@uvm.edu FU National Multiple Sclerosis Society; Biogen Idec; Novartis; Sun Pharma; Celgene Therapeutics; National Institutes of Health; Juvenile Diabetes Research Foundation; Diogenix; Birth of Bioethics FX Andrew J Solomon received a research grant from the National Multiple Sclerosis Society and was a primary investigator in a multicenter clinical trial for a medication sponsored by Biogen Idec.; John R Corboy reports that within the last year he was a primary investigator in a multicenter clinical trial for a medication sponsored by Novartis, Sun Pharma, Celgene Therapeutics, the National Multiple Sclerosis Society, and the National Institutes of Health. He has received research grants from the Juvenile Diabetes Research Foundation, the National Multiple Sclerosis Society, and Diogenix. He has served as a consultant for Novartis, Celgene Therapeutics, Teva Neurosciences, and Biogen Idec. He has received honoraria for speaking engagements from Pro CE, Rocky Mountain MS Center, via Genzyme, and for Grand Rounds at multiple academic institutions. He has been compensated for medical-legal work, as an Editor for Neurology: Clinical Practice, and is an uncompensated board member, NMSS Colorado-Wyoming Chapter.; Eran P Klein has received honoraria for speaking at academic conferences and receives royalty payments for The Birth of Bioethics (Georgetown University Press, 2003). NR 26 TC 1 Z9 1 U1 2 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2015 VL 21 IS 12 BP 1593 EP 1599 DI 10.1177/1352458515569101 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CT1AK UT WOS:000362529200013 PM 25716879 ER PT J AU Shellikeri, S Yunusova, Y Green, JR Pattee, GL Berry, JD Rutkove, SB Zinman, L AF Shellikeri, Sanjana Yunusova, Yana Green, Jordan R. Pattee, Gary L. Berry, James D. Rutkove, Seward B. Zinman, Lorne TI ELECTRICAL IMPEDANCE MYOGRAPHY IN THE EVALUATION OF THE TONGUE MUSCULATURE IN AMYOTROPHIC LATERAL SCLEROSIS SO MUSCLE & NERVE LA English DT Article DE amyotrophic lateral sclerosis; bulbar dysfunction; electrical impedance myography; motor neuron disease; tongue musculature ID NEUROMUSCULAR DISEASE; FUTURE-DIRECTIONS; MOTOR-ASSESSMENT; SKELETAL-MUSCLE; CLINICAL-TRIALS; ALS; STRENGTH; ENDURANCE; BULBAR; AGE AB Introduction: Electrical impedance myography (EIM) quantifies muscle health and is used as a biomarker of muscle abnormalities in neurogenic and myopathic diseases. EIM has yet to be evaluated in the tongue musculature in patients with amyotrophic lateral sclerosis (ALS), who often show clinical bulbar signs. Methods: The lingual musculature of 19 subjects with motor neuron disease and 21 normal participants was assessed using EIM, strength and endurance testing, and clinical assessment. Results: Tongue musculature in the ALS group was characterized by significantly smaller phase (Ph) and greater resistance (R) when compared with the healthy cohort. Ph and tongue endurance were correlated in the ALS group. Conclusions: EIM of tongue musculature could distinguish those with ALS from healthy controls. The demonstrated relationship between tongue function and Ph supports further testing of EIM of the tongue as a potential biomarker in ALS. C1 [Shellikeri, Sanjana; Yunusova, Yana] Univ Toronto, Dept Speech Language Pathol, Toronto, ON, Canada. [Green, Jordan R.] MGH Inst Hlth Profess, Boston, MA USA. [Pattee, Gary L.] Nebraska Med Ctr, Munroe Meyer Inst, Omaha, NE USA. [Berry, James D.] Massachusetts Gen Hosp, MDA ALS Clin, Dept Neurol, Boston, MA 02114 USA. [Rutkove, Seward B.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Rutkove, Seward B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Zinman, Lorne] Univ Toronto, Dept Neurol, Sunnybrook Hlth Sci Ctr, ALS MND Clin, Toronto, ON, Canada. RP Yunusova, Y (reprint author), Univ Toronto, Dept Speech Language Pathol, Toronto, ON, Canada. EM yana.yunusova@utoronto.ca FU National Institute of Deafness and Other Communication Disorders, National Institutes of Health [R01 DC009890, R01 DC0135470]; Canadian Institutes of Health Research [FRN126682]; ALS Society of Canada FX This research was supported by grants from the National Institute of Deafness and Other Communication Disorders, National Institutes of Health (R01 DC009890 and R01 DC0135470); the Canadian Institutes of Health Research (Planning Grant FRN126682); and the ALS Society of Canada (Bernice Ramsey Discovery Grant). NR 58 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2015 VL 52 IS 4 BP 584 EP 591 DI 10.1002/mus.24565 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CT1FY UT WOS:000362544400017 PM 25580728 ER PT J AU Zaidman, CM Wang, LL Connolly, AM Florence, J Wong, BL Parsons, JA Apkon, S Goyal, N Williams, E Escolar, D Rutkove, SB Bohorquez, JL AF Zaidman, Craig M. Wang, Lucy L. Connolly, Anne M. Florence, Julaine Wong, Brenda L. Parsons, Julie A. Apkon, Susan Goyal, Namita Williams, Eugene Escolar, Diana Rutkove, Seward B. Bohorquez, Jose L. CA DART-EIM Clin Evaluators Consortim TI ELECTRICAL IMPEDANCE MYOGRAPHY IN DUCHENNE MUSCULAR DYSTROPHY AND HEALTHY CONTROLS: A MULTICENTER STUDY OF RELIABILITY AND VALIDITY SO MUSCLE & NERVE LA English DT Article DE biomarker; children; Duchenne muscular dystrophy; electrical impedance myography; myopathy ID CLINICAL-TRIALS; ATROPHY; MUSCLE AB Introduction: Electrical impedance myography (EIM) is a non-invasive, painless, objective technique to quantify muscle pathology. Methods: We measured EIM in 8 arm and leg muscles in 61 boys with Duchenne muscular dystrophy (DMD) and 31 healthy boys, ages 3-12 years, at 5 centers. We determined the reliability of EIM and compared results in boys with DMD to controls and to 6-minute walk distance (6MWD), North Star Ambulatory Assessment (NSAA), timed functional tests (TFTs), and strength (hand-held dynamometry). Results: EIM was well tolerated and had good inter-and intrarater reliability (intraclass correlation coefficient 0.81-0.96). The averaged EIM phase value from all muscles was higher (P < 0.001) in controls (10.45 +/- 2.29) than boys with DMD (7.31 +/- 2.23), and correlated (P <= 0.001) with 6MWD (r = 0.55), NSAA (r = 0.66), TFTs (r = -0.56), and strength (r = 0.44). Conclusion: EIM is a reliable and valid measure of disease severity in DMD. Longitudinal studies comparing EIM with other assessments over time in DMD are warranted. C1 [Zaidman, Craig M.; Connolly, Anne M.; Florence, Julaine] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Zaidman, Craig M.; Connolly, Anne M.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Wang, Lucy L.; Bohorquez, Jose L.] Skulpt Inc, Boston, MA USA. [Wong, Brenda L.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. [Parsons, Julie A.] Univ Colorado, Dept Pediat & Neurol, Denver, CO 80202 USA. [Apkon, Susan] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Goyal, Namita] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Williams, Eugene; Escolar, Diana] DART Therapeut Inc, Stockbridge, MA USA. [Rutkove, Seward B.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Zaidman, CM (reprint author), Washington Univ, Sch Med, Dept Neurol, 660 South Euclid Ave,Box 8111, St Louis, MO 63110 USA. EM zaidmanc@neuro.wustl.edu OI Wang, Lucy Lu/0000-0001-8752-6635 FU DART Therapeutics FX E.W. and D.E. were employed by DART Therapeutics, which supported this study. S.B.R. has equity in, and serves a consultant and scientific advisor to, Skulpt, Inc., a company that designs impedance devices for clinical and research use; he is also a member of the company's board of directors. The company also has an option to license patented impedance technology, for which S.B.R. has been named as an inventor. J.L.B. has ownership in Skulpt, Inc., the manufacturer of the EIM device used in this study. NR 16 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2015 VL 52 IS 4 BP 592 EP 597 DI 10.1002/mus.24611 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CT1FY UT WOS:000362544400018 PM 25702806 ER PT J AU Paganoni, S Schoenfeld, D Shui, A Cudkowicz, M Miller, TM AF Paganoni, Sabrina Schoenfeld, David Shui, Amy Cudkowicz, Merit Miller, Timothy M. TI PRE-MORBID TYPE 2 DIABETES MELLITUS AS A PROGNOSTIC FACTOR IN AMYOTROPHIC LATERAL SCLEROSIS REPLY SO MUSCLE & NERVE LA English DT Letter C1 [Paganoni, Sabrina; Cudkowicz, Merit] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst, Boston, MA 02134 USA. [Schoenfeld, David; Shui, Amy] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Miller, Timothy M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Paganoni, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst, Boston, MA 02134 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2015 VL 52 IS 4 BP 691 EP 691 DI 10.1002/mus.24760 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CT1FY UT WOS:000362544400038 PM 26138218 ER PT J AU Luo, CW Knight, R Siljander, H Knip, M Xavier, RJ Gevers, D AF Luo, Chengwei Knight, Rob Siljander, Heli Knip, Mikael Xavier, Ramnik J. Gevers, Dirk TI ConStrains identifies microbial strains in metagenomic datasets SO NATURE BIOTECHNOLOGY LA English DT Article ID GENOME SEQUENCE; GUT MICROBIOTA; MARKER GENES; COLONIZATION AB An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived datasets provides insights into microbial community dynamics. C1 [Luo, Chengwei; Xavier, Ramnik J.; Gevers, Dirk] Broad Inst Massachusetts Inst Technol MIT & Harva, Cambridge, MA 02142 USA. [Luo, Chengwei; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Luo, Chengwei; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Luo, Chengwei; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA. [Luo, Chengwei; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. [Siljander, Heli; Knip, Mikael] Univ Helsinki, Childrens Hosp, Helsinki, Finland. [Siljander, Heli; Knip, Mikael] Helsinki Univ Hosp, Helsinki, Finland. [Siljander, Heli] Univ Helsinki, Diabet & Obes, Res Programs Unit, Helsinki, Finland. [Knip, Mikael] Folkhalsan Res Ctr, Helsinki, Finland. [Knip, Mikael] Tampere Univ Hosp, Dept Pediat, Tampere, Finland. [Xavier, Ramnik J.] MIT, Ctr Microbiome Informat & Therapeut, Cambridge, MA 02139 USA. RP Xavier, RJ (reprint author), Broad Inst Massachusetts Inst Technol MIT & Harva, Cambridge, MA 02142 USA. EM xavier@molbio.mgh.harvard.edu; dirk.gevers@gmail.com RI Knight, Rob/D-1299-2010; OI Knip, Mikael/0000-0003-0474-0033 FU Crohn's and Colitis Foundation of America; Leona M. and Harry B. Helmsley Charitable Trust; US National Institutes of Health [U54 DK102557, R01 DK092405]; Howard Hughes Medical Institute; Finnish Centre of Excellence in Molecular Systems Immunology and Physiology Research (Academy of Finland) [250114] FX We thank N. Nedelsky for editorial support. This work was supported in part by the Crohn's and Colitis Foundation of America, the Leona M. and Harry B. Helmsley Charitable Trust, US National Institutes of Health grants U54 DK102557 (R.J.X.) and R01 DK092405 (R.J.X.)., the Howard Hughes Medical Institute (R.K.) and the Finnish Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012-17 (Academy of Finland, Decision No. 250114; M.K.). NR 40 TC 31 Z9 31 U1 3 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2015 VL 33 IS 10 BP 1045 EP + DI 10.1038/nbt.3319 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CT1JX UT WOS:000362555700023 PM 26344404 ER PT J AU Ren, X Moser, PT Gilpin, SE Okamoto, T Wu, T Tapias, LF Mercier, FE Xiong, LJ Ghawi, R Scadden, DT Mathisen, DJ Ott, HC AF Ren, Xi Moser, Philipp T. Gilpin, Sarah E. Okamoto, Tatsuya Wu, Tong Tapias, Luis F. Mercier, Francois E. Xiong, Linjie Ghawi, Raja Scadden, David T. Mathisen, Douglas J. Ott, Harald C. TI Engineering pulmonary vasculature in decellularized rat and human lungs SO NATURE BIOTECHNOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; ORTHOTOPIC TRANSPLANTATION; LUMEN FORMATION; MATRIX; PERMEABILITY; PROGENITORS; TISSUE; DIFFERENTIATION; MORPHOGENESIS; REGENERATION AB Bioengineered lungs produced from patient-derived cells may one day provide an alternative to donor lungs for transplantation therapy. Here we report the regeneration of functional pulmonary vasculature by repopulating the vascular compartment of decellularized rat and human lung scaffolds with human cells, including endothelial and perivascular cells derived from induced pluripotent stem cells. We describe improved methods for delivering cells into the lung scaffold and for maturing newly formed endothelium through co-seeding of endothelial and perivascular cells and a two-phase culture protocol. Using these methods we achieved similar to 75% endothelial coverage in the rat lung scaffold relative to that of native lung. The regenerated endothelium showed reduced vascular resistance and improved barrier function over the course of in vitro culture and remained patent for 3 days after orthotopic transplantation in rats. Finally, we scaled our approach to the human lung lobe and achieved efficient cell delivery, maintenance of cell viability and establishment of perfusable vascular lumens. C1 [Ren, Xi; Moser, Philipp T.; Gilpin, Sarah E.; Okamoto, Tatsuya; Wu, Tong; Tapias, Luis F.; Mercier, Francois E.; Xiong, Linjie; Ghawi, Raja; Scadden, David T.; Ott, Harald C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Ren, Xi; Moser, Philipp T.; Gilpin, Sarah E.; Okamoto, Tatsuya; Wu, Tong; Tapias, Luis F.; Mercier, Francois E.; Xiong, Linjie; Ghawi, Raja; Scadden, David T.; Mathisen, Douglas J.; Ott, Harald C.] Harvard Univ, Sch Med, Boston, MA USA. [Tapias, Luis F.; Mathisen, Douglas J.; Ott, Harald C.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Ghawi, Raja] Harvard Univ, Cambridge, MA USA. [Scadden, David T.; Ott, Harald C.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Ott, HC (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM hott@mgh.harvard.edu FU United Therapeutics Corporation; National Institutes of Health (NIH) Director's New Innovator Award [DP2-OD008749-01] FX This study was supported by the United Therapeutics Corporation and the National Institutes of Health (NIH) Director's New Innovator Award (DP2-OD008749-01). The authors thank the HSCI/MGH Flow Cytometry Core Facility for analysis and purification of hiPSC differentiation, the MGH Center for Skeletal Research Core (NIH P30 AR066261) for histological processing and MGH Wellman Center for Photomedicine for transmission electron microscopy. NR 39 TC 25 Z9 25 U1 4 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2015 VL 33 IS 10 BP 1097 EP + DI 10.1038/nbt.3354 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CT1JX UT WOS:000362555700031 PM 26368048 ER PT J AU Jovanovich, A Chonchol, M AF Jovanovich, Anna Chonchol, Michel TI Reductions in FGF-23 levels associated with improved outcomes SO NATURE REVIEWS NEPHROLOGY LA English DT News Item ID DISEASE AB Elevated levels of fibrobast growth factor 23 (FGF-23) are associated with cardiovascular and all-cause mortality in patients with kidney disease. A secondary analysis of the EVOLVE trial reports that cinacalcet-induced reductions in FGF-23 were associated with a reduced risk of cardiovascular events in patients with secondary hyperparathyroidism on dialysis. C1 [Jovanovich, Anna] Denver VA Med Ctr, Med Serv, Renal Sect, Denver, CO 80220 USA. [Chonchol, Michel] Univ Colorado Denver, Anschutz Med Ctr, Div Renal Dis & Hypertens, Aurora, CO 80045 USA. RP Chonchol, M (reprint author), Univ Colorado Denver, Anschutz Med Ctr, Div Renal Dis & Hypertens, 13199 East Montview Blvd,Suite 495, Aurora, CO 80045 USA. EM michel.chonchol@ucdenver.edu NR 10 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 EI 1759-507X J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD OCT PY 2015 VL 11 IS 10 BP 572 EP 573 DI 10.1038/nrneph.2015.125 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CT3GN UT WOS:000362695300003 PM 26215510 ER PT J AU Cortazar, FB Stone, JH AF Cortazar, Frank B. Stone, John H. TI IgG4-related disease and the kidney SO NATURE REVIEWS NEPHROLOGY LA English DT Review ID IDIOPATHIC RETROPERITONEAL FIBROSIS; SERUM IGG4 CONCENTRATIONS; TUBULOINTERSTITIAL NEPHRITIS; SYSTEMIC-DISEASE; AUTOIMMUNE PANCREATITIS; MEMBRANOUS NEPHROPATHY; CLINICOPATHOLOGICAL-ENTITY; SCLEROSING PANCREATITIS; THERAPY; GLOMERULONEPHRITIS AB IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition that involves almost every organ system. In this Review, we summarize current knowledge of IgG4-RD and its most frequent manifestations in the kidney IgG4-related tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). Diagnosis of IgG4-RD relies on histopathology: the typical features are a dense lymphoplasmacytic infiltrate and storiform fibrosis. A high percentage of plasma cells observed within lesions stain positively for IgG4. IgG4-related TIN bears the hallmark pathological findings of IgG4-RD; distinctive radiographic characteristics are also frequently observed with use of contrast-enhanced CT. MGN secondary to IgG4-RD seems to be distinct from idiopathic MGN. Humoral and cell-mediated immunity seem to have roles in the pathophysiology of IgG4-RD, but the details of these roles remain unclear. The IgG4 molecule itself is unlikely to be the primary driver of inflammation; rather, it probably downregulates the immune response. Fibrosis might be caused by activation of innate immune cells by polarized CD4(+) T cells. Glucocorticoids are the standard initial treatment for IgG4-RD, but their long-term adverse effects and the high frequency of relapse and renal damage associated with use of this treatment has prompted a search for more effective options. B-cell depletion and the targeting of plasmablasts are both promising approaches. C1 [Cortazar, Frank B.] Massachusetts Gen Hosp, Nephrol Unit, Boston, MA 02114 USA. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@mgh.harvard.edu NR 52 TC 9 Z9 10 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 EI 1759-507X J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD OCT PY 2015 VL 11 IS 10 BP 599 EP 609 DI 10.1038/nrneph.2015.95 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA CT3GN UT WOS:000362695300007 PM 26122730 ER PT J AU Zhao, W Wang, J Bi, WN Ferruzzi, M Yemul, S Freire, D Mazzola, P Ho, L Dubner, L Pasinetti, GM AF Zhao, Wei Wang, Jun Bi, Weina Ferruzzi, Mario Yemul, Shrishailam Freire, Daniel Mazzola, Paolo Ho, Lap Dubner, Lauren Pasinetti, Giulio Maria TI Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE Sleep deprivation; Polyphenols; Cognitive dysfunction; Resilience; Memory consolidation ID GREEN TEA CATECHINS; ALZHEIMERS-DISEASE; MOUSE MODEL; SYNAPTIC PLASTICITY; S6 KINASE; MEMORY; METABOLISM; HIPPOCAMPUS; DISORDERS; PATHWAY AB Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Zhao, Wei; Wang, Jun; Bi, Weina; Yemul, Shrishailam; Freire, Daniel; Mazzola, Paolo; Ho, Lap; Dubner, Lauren; Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Geriatr, New York, NY 10029 USA. [Zhao, Wei; Wang, Jun; Bi, Weina; Ho, Lap; Pasinetti, Giulio Maria] James J Peter VA Med Ctr, Geriatr Res Educ Clin Ctr, Bronx, NY USA. [Ferruzzi, Mario] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA. [Mazzola, Paolo] Univ Milano Bicocca, Dept Hlth Sci, Monza, Italy. RP Pasinetti, GM (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu OI Mazzola, Paolo/0000-0002-0484-1136 FU Icahn School of Medicine at Mount Sinai; National Center for Complementary and Integrative Health (NCCIH) [P50 AT008661-01]; Office of Dietary Supplements (ODS) FX This study was supported by discretionary funding from the Icahn School of Medicine at Mount Sinai to Dr. Giulio Pasinetti. In addition, Dr. Pasinetti holds a Career Scientist Award in the Research and Development unit and is the Director of the Basic and Biomedical Research and Training Program, GRECC, James J. Peters Veterans Affairs Medical Center. We acknowledge that the contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. This publication was supported by Grant Number P50 AT008661-01, titled "Dietary Botanicals in the Preservation of Cognitive and Psychological Resilience," from the National Center for Complementary and Integrative Health (NCCIH) and the Office of Dietary Supplements (ODS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCIH, ODS, or the National Institutes of Health. NR 47 TC 0 Z9 0 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 EI 1872-9754 J9 NEUROCHEM INT JI Neurochem. Int. PD OCT PY 2015 VL 89 BP 191 EP 197 DI 10.1016/j.neuint.2015.07.023 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CT2CO UT WOS:000362609800020 PM 26235983 ER PT J AU Naunheim, MR Kozin, ED Sethi, RK Ota, HG Gray, ST Shrime, MG AF Naunheim, Matthew R. Kozin, Elliot D. Sethi, Rosh K. Ota, H. Gregory Gray, Stacey T. Shrime, Mark G. TI Cost-Benefit Analysis of an Otolaryngology Emergency Room Using a Contingent Valuation Approach SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE cost-benefit analysis; contingent valuation; willingness to pay; emergency services; specialty emergency rooms ID WILLINGNESS-TO-PAY; HEALTH-CARE-DELIVERY; ALLERGIC RHINITIS; GENERAL-PRACTICE; PAYMENT SCALE; ENT PROBLEMS; MODEL; QUALITY; COMMUNITY; CONTRACT AB Objectives Dedicated otolaryngology emergency rooms (ERs) provide a unique mechanism of health care delivery. Relative costs and willingness to pay (WTP) for these services have not been studied. This study aims to provide a cost-benefit analysis of otolaryngology-specific ER care. Study Design Cost-benefit analysis based on contingent valuation surveys. Setting An otolaryngology-specific ER in a tertiary care academic medical center. Subjects and Methods Adult English-speaking patients presenting to an otolaryngology ER were included. WTP questions were used to assess patient valuations of specialty emergency care. Sociodemographic data, income, and self-reported levels of distress were assessed. State-level and institution-specific historical cost data were merged with WTP data within a cost-benefit analysis framework. Results The response rate was 75.6%, and 199 patients were included in the final analysis. Average WTP for otolaryngology ER services was $319 greater than for a general ER (95% CI: $261 to $377), with a median value of $200. The historical mean cost per visit at a general ER was $575, and mean cost at the specialty ER was $551 (95% CI: $529 to $574). Subtracting incremental cost from incremental WTP yielded a net benefit of $343. Conclusion Dedicated otolaryngology ER services are valued by patients for acute otolaryngologic problems and have a net benefit of $343 per patient visit. They appear to be a cost-beneficial method for addressing acute otolaryngologic conditions. This study has implications for ER-based otolaryngologic care and direct-to-specialist services. C1 [Naunheim, Matthew R.; Kozin, Elliot D.; Sethi, Rosh K.; Ota, H. Gregory; Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Naunheim, Matthew R.; Kozin, Elliot D.; Sethi, Rosh K.; Ota, H. Gregory; Gray, Stacey T.; Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Global Hlth & Populat, Boston, MA USA. RP Naunheim, MR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Matthew_Naunheim@meei.harvard.edu NR 51 TC 2 Z9 2 U1 0 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2015 VL 153 IS 4 BP 575 EP 581 DI 10.1177/0194599815596742 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CS9XD UT WOS:000362445800018 PM 26216886 ER PT J AU Parker, NP Barbu, AM Hillman, RE Zeitels, SM Burns, JA AF Parker, Noah P. Barbu, Anca M. Hillman, Robert E. Zeitels, Steven M. Burns, James A. TI Revision Transcervical Medialization Laryngoplasty for Unilateral Vocal Fold Paralysis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE vocal cord; paralysis; dysphonia; revision; laryngoplasty ID ARYTENOID ADDUCTION; GORE-TEX; THYROPLASTY; EXPERIENCE; IMPLANTS; VOICE AB Objective To identify patterns of failure following transcervical medialization laryngoplasty for unilateral vocal fold paralysis and describe indications and revision techniques for optimal vocal outcomes. Study Design Case series with chart review. Setting Tertiary care center. Subjects and Methods Thirty-nine consecutive patients between January 2005 and April 2014 undergoing transcervical revision of failed primary medialization laryngoplasty were identified. Demographics, etiology, stroboscopic assessment, and surgical techniques were recorded. Patient self-assessment using the Voice-Related Quality-of-Life (VRQOL) questionnaire and objective acoustic and aerodynamic assessments performed pre- and postoperatively were analyzed using t tests for paired comparisons. Results Thirty-nine patients underwent 48 transcervical revision surgeries. Median follow-up was 14.6 months from time of final revision surgery. Indications included anterior glottic incompetence (38/48, 79%), posterior glottic incompetence (20/48, 42%), glottic overclosure (8/48, 17%), and/or decreased phonatory pliability (12/48, 25%). A combination of findings was present in 21 (44%) surgeries. Revision techniques included either anterior augmentation, arytenopexy, and cricothyroid subluxation (alone or in combination) in 46 of 48 (96%) patients or partial implant removal alone in 2 patients. Seven patients (18%) required multiple revisions. A complete set of voice parameters was available for 22 patients, and statistically significant improvements included VRQOL scores, fundamental frequency in females, jitter, noise-to-harmonic ratio, and mean airflow rate. Conclusion Patterns of failure in patients with suboptimal phonatory function after transcervical medialization laryngoplasty included persistent glottic incompetence, glottic overclosure, and decreased vocal fold pliability. Revision transcervical medialization surgery, guided by individualized consideration of vocal fold position and surface pliability, can improve phonatory outcomes. C1 [Parker, Noah P.; Barbu, Anca M.; Hillman, Robert E.; Zeitels, Steven M.; Burns, James A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Parker, Noah P.; Barbu, Anca M.; Hillman, Robert E.; Zeitels, Steven M.; Burns, James A.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Burns, JA (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, One Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM Burns.James@MGH.Harvard.edu NR 24 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2015 VL 153 IS 4 BP 593 EP 598 DI 10.1177/0194599815585091 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CS9XD UT WOS:000362445800021 PM 25968059 ER PT J AU Dedmon, MM Kozin, ED Lee, DJ AF Dedmon, Matthew M. Kozin, Elliott D. Lee, Daniel J. TI Development of a Temporal Bone Model for Transcanal Endoscopic Ear Surgery SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE endoscopic ear surgery; transcanal; dissection model; cholesteatoma ID RANDOMIZED-CONTROLLED-TRIAL; INTRANASAL ETHMOIDECTOMY; COMPLICATIONS; PERFORMANCE; IMPROVES AB Transcanal endoscopic ear surgery (TEES) is being increasingly used in chronic ear disease for cholesteatoma removal and middle ear reconstruction, reducing the need for a postauricular incision and mastoidectomy. However, TEES is a challenging technique even for the most experienced otologist, requiring one-handed dissection using angled instrumentation. We have therefore developed a high-fidelity dissection model incorporating key aspects of TEES and cholesteatoma removal to facilitate the acquisition of these skills. Artificial cholesteatoma was implanted into middle ear spaces of a human temporal bone via a facial recess approach. A pilot study was conducted whereby surgeons endoscopically elevated a tympanomeatal flap with artificial bleeding and removed artificial cholesteatoma with angled instrumentation. Surgeons were uniformly satisfied with the experience and felt it would translate into improved performance in the operating room. This study suggests that the TEES dissection model could become an integral tool in the training of emerging TEES techniques. C1 [Dedmon, Matthew M.; Kozin, Elliott D.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Dedmon, Matthew M.; Kozin, Elliott D.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otorhinolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Dedmon, MM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM matthew_dedmon@meei.harvard.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2015 VL 153 IS 4 BP 613 EP 615 DI 10.1177/0194599815593738 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CS9XD UT WOS:000362445800024 PM 26183525 ER EF