FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fitzsimons, MG Dilley, JD Moser, C Walker, JD AF Fitzsimons, Michael G. Dilley, Joshua D. Moser, Chris Walker, Jennifer D. TI Analysis of 43 Intraoperative Cardiac Surgery Case Cancellations SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE anesthesia; health economics; patient safety; case cancellation; complications ID OPERATING-ROOM; CANNULATION AB Objective: Late cancellation of surgery cases imposes significant emotional distress on the patient and their family and results in wasted resources, including loss of operating room and personnel time. This study was designed to determine the causes of cancellation, preventability, total operating room time, and postoperative destination. Design: This study was a retrospective review of the 43 cardiac surgical cases that were cancelled while the patient was in the operating room (OR) but prior to surgical incision. Setting: The cases were performed at the Massachusetts General Hospital, a teaching hospital of Harvard Medical School. Participants: Forty-three out of 5,110 scheduled cardiac cases were identified that were cancelled after the patient had entered the operating room between January 1, 2010 and December 31, 2013. Interventions: No interventions were made. This was a retrospective study. Measurements and Main Results: The most common causes of cancellation included a change in the patient's health status (44%), problems associated with central catheter placement (18.6%), and unsatisfactory donor organs for planned transplantation (12%). The majority were inpatients (65%) prior to the procedure. The cumulative OR time for all cancelled cases was 5,374 minutes (89 hours and 34 minutes). Conclusions: The reason for cancellation, preventability, total operating room time, and postoperative destination were determined. The information can be utilized to decrease the number of future cancellations. (C) 2016 Elsevier Inc. All rights reserved. C1 [Fitzsimons, Michael G.; Dilley, Joshua D.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. [Moser, Chris] Lahey Hosp & Med Ctr, Dept Anesthesiol, Burlington, MA USA. [Walker, Jennifer D.] UMass Mem Med Ctr, Dept Cardiac Surg, Univ Campus, Worcester, MA USA. RP Dilley, JD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM joshuaddilley@gmail.com NR 15 TC 0 Z9 0 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 1053-0770 EI 1532-8422 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD FEB PY 2016 VL 30 IS 1 BP 19 EP 22 DI 10.1053/j.jvca.2015.08.007 PG 4 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA DD7KT UT WOS:000370104100004 PM 26597766 ER PT J AU Dai, DW Singh, I Hershman, JM AF Dai, David W. Singh, Ishita Hershman, Jerome M. TI Lozenge-Induced Hypermineralcorticoid State--A Unique Case of Licorice Lozenges Resulting in Hypertension and Hypokalemia SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID CORTISOL; RECEPTOR C1 [Singh, Ishita] Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Singh, I (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.; Singh, I (reprint author), West Los Angeles VA Med Ctr, VA Greater Los Angeles Healthcare Syst, Endocrinol 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM isingh@mednet.ucla.edu NR 13 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD FEB PY 2016 VL 18 IS 2 BP 159 EP 160 DI 10.1111/jch.12633 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DD5SQ UT WOS:000369985100013 PM 26212733 ER PT J AU Schonfeld, DJ Shekunov, J Jellinek, M Stein, MT AF Schonfeld, David J. Shekunov, Julia Jellinek, Michael Stein, Martin T. TI A 9-Year-Old Girl Discovers That Her Mother Was Murdered SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material DE bereavement; loss of parent; guilt; funeral participation; internal representation ID CHILDHOOD BEREAVEMENT; DEATH AB CASE: Susan was a 9-year-old girl living with her mother; she had never met her father. Her mother returned one evening from her job as a cocktail waitress and Susan met her at the apartment door to let her know they had run out of cat food. Her mother said she would go and buy some the next morning because it was late and she was tired, but Susan insisted she go out that evening because the cat had not eaten all day. Her mother was fatally shot in the parking lot of the convenience store shortly thereafter; since there was no robbery involved, the police suspected it was someone that she knew. Susan's extended family had her move out of the apartment that evening and relocate to live with her aunt and uncle out-of-state. The transition happened quickly. Susan was unable to return to her apartment to pick up any additional belongings and never returned to say goodbye to her friends. The family decided she was too young to attend the funeral.Susan had trouble fitting in with her aunt and uncle's family; they had 2 children who were 8 and 6 years old, and Susan felt she was being treated like a baby. She resented having a bedtime (her mother allowed her to stay up as late as she wished), and she complained that the work at school was boring and her classmates were childish. When the family went to a festival in town, she left abruptly without telling them, which frightened Susan's aunt and uncle. They wanted to be supportive but felt that she needed more structure than her mother had provided her. Susan's aunt and uncle sought bereavement support for Susan from her pediatrician and parenting advice for themselves. C1 [Schonfeld, David J.] Univ So Calif, Sch Social Work, Natl Ctr Sch Crisis & Bereavement, Los Angeles, CA 90089 USA. [Schonfeld, David J.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Shekunov, Julia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jellinek, Michael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Stein, Martin T.] Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA 92103 USA. RP Schonfeld, DJ (reprint author), Univ So Calif, Sch Social Work, Natl Ctr Sch Crisis & Bereavement, Los Angeles, CA 90089 USA.; Schonfeld, DJ (reprint author), Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NR 2 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 FEB-MAR PY 2016 VL 37 IS 2 BP 172 EP 174 DI 10.1097/DBP.0000000000000254 PG 3 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA DD5OG UT WOS:000369973000009 PM 26760376 ER PT J AU van Leeuwen, WF Oflazoglu, K Menendez, ME Ring, D AF van Leeuwen, Wouter F. Oflazoglu, Kamilcan Menendez, Mariano E. Ring, David TI Negative Ulnar Variance and Kienbock Disease SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Kienbock disease; lunatomalacia; ulnar variance ID INTRAOSSEOUS PRESSURE; POPULATION; MORPHOLOGY AB Purpose To test the primary null hypothesis that there is no difference in mean ulnar variance (UV) scaled to the length of the capitates between 166 wrists with Kienbock disease and an equal number of matched controls and to test the secondary null hypothesis that mean scaled UV does not vary based on age, sex, or race in both Kienbock and control wrists. Methods Ulnar variance was measured on posteroanterior radiographs of the wrist as the distance between a line through the midpoint between the volar and the dorsal edges of the ulnar margin of the radius and a line tangential to the most distal aspect of the carpal surface of the head of the ulna, both perpendicular to the longitudinal axis of the radius. Measurement of UV was scaled to the length of the capitate, resulting in a UV to capitate height (UV:CH) ratio. Results We found a significant difference in mean UV:CH ratio between patients with Kienbock disease and a control group matched by age, sex, race, and limb. The prevalence of negative UV was high in both patients with Kienbock disease and matched controls. There were no differences in mean UV:CH ratio with respect to age, sex, or race among patients with Kienbock disease or matched controls. Conclusions The precise role of ulna minus in the development of Kienbock disease remains uncertain and unanswered, given that many patients with Kienbock disease have neutral or positive UV. In addition, a large proportion of the normal population has negative UV, whereas Kienbock disease is rare. (Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved.) Type of study/level of evidence Prognostic III. C1 [van Leeuwen, Wouter F.; Oflazoglu, Kamilcan; Menendez, Mariano E.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Hand & Upper Extrem Serv, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 31 TC 2 Z9 3 U1 2 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 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD FEB PY 2016 VL 41 IS 2 BP 214 EP 218 DI 10.1016/j.jhsa.2015.10.014 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DD2UJ UT WOS:000369777400008 PM 26686062 ER PT J AU Parrish, RC Menendez, ME Mudgal, CS Jupiter, JB Chen, NC Ring, D AF Parrish, Raymond C., II Menendez, Mariano E. Mudgal, Chaitanya S. Jupiter, Jesse B. Chen, Neal C. Ring, David TI Patient Satisfaction and its Relation to Perceived Visit Duration With a Hand Surgeon SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Doctor rush; empathy; expectations; patient satisfaction; visit duration ID EMPATHY CARE MEASURE; PREOPERATIVE EXPECTATIONS; CONSUMER ASSESSMENT; PATIENTS PERCEPTION; HEALTH LITERACY; SPINE SURGERY; TIME SPENT; ITEM BANK; PHYSICIAN; OUTCOMES AB Purpose To determine whether patient perception of time spent with a hand surgeon relates to patient satisfaction after a single new-patient office visit. Methods Prior to each visit, 112 consecutive new patients predicted how much time they expected to spend with the surgeon. Following the visit, patients were asked to estimate the time spent with the surgeon, indicate whether the surgeon appeared rushed, and rate their overall satisfaction with the surgeon. Wait time and actual visit duration were measured. Patients also completed a sociodemographic survey, the Consultation and Relational Empathy Measure, the Newest Vital Sign Health Literacy test, and 3 Patient-Reported Outcomes Measurement Information System-based questionnaires: Upper Extremity Function, Pain Interference, and Depression. Multivariable logistic and linear regression models were used to determine predictors of patient satisfaction, patient-perceived surgeon rush, and high previsit expectations of visit duration. Results Patient satisfaction was not associated with perceived visit duration but did correlate strongly with patient-rated surgeon empathy and symptoms of depression. Neither visit duration nor previsit expectations of visit length were determinants of patient-perceived surgeon rush. Only surgeon empathy was associated. Less-educated patients anticipated needing more time with the surgeon. Conclusions Patient satisfaction with the surgeon and with the time spent during the office visit was primarily linked to surgeon empathy rather than to visit duration or previsit expectation of visit length. Efforts to make hand surgery office visits more patient-centered should focus on improving dialogue quality, and not necessarily on making visits longer. Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved. C1 [Parrish, Raymond C., II; Menendez, Mariano E.; Mudgal, Chaitanya S.; Jupiter, Jesse B.; Chen, Neal C.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 32 TC 3 Z9 3 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD FEB PY 2016 VL 41 IS 2 BP 257 EP 262 DI 10.1016/j.jhsa.2015.11.015 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DD2UJ UT WOS:000369777400015 PM 26718069 ER PT J AU Oflazoglu, K Mellema, JJ Menendez, ME Mudgal, CS Ring, D Chen, NC AF Oflazoglu, Kamilcan Mellema, Jos J. Menendez, Mariano E. Mudgal, Chaitanya S. Ring, David Chen, Neal C. TI Prevalence of and Factors Associated With Major Depression in Patients With Upper Extremity Conditions SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Depression; hand; orthopedics; prevalence; upper extremity ID ORTHOPEDIC TRAUMA PATIENTS; ITEM BANK; OUTCOMES; PAIN; DISABILITY; SEVERITY; SYMPTOMS; INJURY; PHQ-9 AB Purpose To determine the prevalence of an estimated diagnosis of major depression in patients with upper extremity conditions and factors that help identify patients who might benefit from psychological treatment. Methods In this observational cross-sectional study, 190 patients completed questionnaires measuring symptoms of depression with the Patient Health Questionnaire, upper extremity disability with the Patient-Reported Outcomes Measurement Information System Upper Extremity, pain interference with the Patient-Reported Outcomes Measurement Information System Pain Interference, and health anxiety with the Short Health Anxiety Inventory. Results The estimated prevalence of an estimated diagnosis of major depression (Patient Health Questionnaire 9 >= 10) among this group of patients was 12%. Having multiple pain conditions, a history of depression, and greater limitation from pain for daily activities were independently associated with an estimated diagnosis of major depression. Conclusions The finding that 1 in 8 patients presenting to a hand surgeon have untreated or undertreated symptoms of depression sufficient to qualify for an estimated diagnosis of major depression emphasizes the importance of assessing for depression at all levels of care. Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved. C1 [Oflazoglu, Kamilcan; Mellema, Jos J.; Menendez, Mariano E.; Mudgal, Chaitanya S.; Ring, David; Chen, Neal C.] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp,Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partnets.org OI Ring, David/0000-0002-6506-4879 NR 31 TC 0 Z9 0 U1 3 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD FEB PY 2016 VL 41 IS 2 BP 263 EP 269 DI 10.1016/j.jhsa.2015.11.019 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DD2UJ UT WOS:000369777400016 PM 26723479 ER PT J AU Calderwood, AH Schroy, PC Kluge, MA Cabral, HJ Burgess, JF AF Calderwood, Audrey H. Schroy, Paul C., III Kluge, Matthew A. Cabral, Howard J. Burgess, James F., Jr. TI Predictors of Adherence to Post-Polypectomy Surveillance Colonoscopy SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Adherence; screening; colorectal cancer; ambulatory care ID SOCIETY TASK-FORCE; AMERICAN-CANCER-SOCIETY; COLORECTAL-CANCER; CONSENSUS UPDATE; MEDICARE BENEFICIARIES; ADENOMATOUS POLYPS; GUIDELINES; POPULATION; PREVENTION; RESECTION AB Objective. To identify predictors of adherence with surveillance colonoscopy at a safety-net hospital. Methods. We evaluated average-risk patients aged 50-75 with adenomas diagnosed at screening colonoscopy between 1/1/05-12/31/07. The primary outcome was on-time follow-up defined as attendance at surveillance colonoscopy within 5.5 years of screening colonoscopy. Results. Among 881 patients, of whom 38% were English-speaking non-Hispanic Blacks, 38.3% attended on-time surveillance colonoscopy. In unadjusted analyses, >= 3 PCP visits after baseline colonoscopy (OR 3.6 [2.5-5.0]), "adenoma" on the EMR problem list (OR 2.2 [1.6-2.9]), and Charlson Index >= 1 (OR 1.4 [1.0-1.8]) were associated with adherence. "Adenoma" on the EMR problem list remained significant in multivariable analyses (aOR 1.8 [1.3-2.5]). A significant interaction was observed between ethnicity/language and PCP visits (p=.003). Conclusion. Many adenoma-bearing patients fail to attend surveillance colonoscopy in a safety-net setting. Adding "adenomas" to the EMR problem list improved attendance, suggesting that system-level interventions can increase adherence. C1 [Calderwood, Audrey H.; Schroy, Paul C., III] Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, Boston, MA 02215 USA. [Kluge, Matthew A.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Cabral, Howard J.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Boston, MA USA. [Burgess, James F., Jr.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. RP Calderwood, AH (reprint author), Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, Boston, MA 02215 USA.; Calderwood, AH (reprint author), 85 East Concord St,Room 7724, Boston, MA 02118 USA. EM Audrey.calderwood@bmc.org NR 39 TC 0 Z9 0 U1 1 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 EI 1548-6869 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2016 VL 27 IS 1 BP 261 EP 279 DI 10.1353/hpu.2016.0028 PG 19 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DC9BD UT WOS:000369514400022 PM 27763469 ER PT J AU Hochman, M Briggs-Malonson, M Wilkes, E Bergman, J Daskivich, LP Moin, T Brook, I Ryan, GW Brook, RH Mangione, CM AF Hochman, Michael Briggs-Malonson, Medell Wilkes, Erin Bergman, Jonathan Daskivich, Lauren Patty Moin, Tannaz Brook, Ilanit Ryan, Gery W. Brook, Robert H. Mangione, Carol M. TI Fostering a Commitment to Quality: Best Practices in Safety-net Hospitals SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Quality improvement; safety-net; community ID HEALTH REFORM; OF-CARE; 1990S AB In 2007, the Martin Luther King, Jr.-Harbor Hospital (MLK-Harbor), which served a large safety-net population in South Los Angeles, closed due to quality challenges. Shortly thereafter, an agreement was made to establish a new hospital, Martin Luther King, Jr. Community Hospital (MLKCH), to serve the unmet needs of the community. To assist the newly appointed MLKCH Board of Directors in building a culture of quality, we conducted a series of interviews with five high-performing hospital systems. In this report, we describe our findings. The hospitals we interviewed achieved a culture of quality by: 1) developing guiding principles that foster quality; 2) hiring and retaining personnel who are stewards of quality; 3) promoting efficient resource utilization; 4) developing a well-organized quality improvement infrastructure; and 5) cultivating integrated, patient-centric care. The institutions highlighted in this report provide important lessons for MLKCH and other safety-net institutions. C1 [Hochman, Michael; Bergman, Jonathan; Daskivich, Lauren Patty; Brook, Robert H.; Mangione, Carol M.] Univ Calif Los Angeles, Robert Wood Johnson Fdn, Clin Scholars Program, Los Angeles, CA USA. [Hochman, Michael; Daskivich, Lauren Patty] US Dept Vet Affairs, Los Angeles, CA USA. [Hochman, Michael] AltaMed Hlth Serv, 2040 Camfield Ave, Los Angeles, CA 90040 USA. [Briggs-Malonson, Medell] Univ Calif Los Angeles, David Geffen Sch Med, Robert Wood Johnson Fdn, Clin Scholars Program, Los Angeles, CA 90095 USA. [Briggs-Malonson, Medell] Martin Luther King Jr Community Hosp, Los Angeles, CA USA. [Wilkes, Erin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Wilkes, Erin; Daskivich, Lauren Patty] Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA. [Bergman, Jonathan] US Dept Vet Affairs, Vet Hlth Affairs, Los Angeles, CA USA. [Bergman, Jonathan] Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. [Moin, Tannaz] Univ Calif Los Angeles, David Geffen Sch Med, Vet Hlth Affairs, Los Angeles, CA USA. [Brook, Ilanit] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA. [Ryan, Gery W.] Pardee RAND Grad Sch, Santa Monica, CA USA. [Brook, Robert H.] Univ Calif Los Angeles, David Geffen Sch Med, US Dept Vet Affairs, Pardee RAND Grad Sch, Los Angeles, CA 90095 USA. [Brook, Robert H.; Mangione, Carol M.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Hochman, M (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Fdn, Clin Scholars Program, Los Angeles, CA USA.; Hochman, M (reprint author), US Dept Vet Affairs, Los Angeles, CA USA.; Hochman, M (reprint author), AltaMed Hlth Serv, 2040 Camfield Ave, Los Angeles, CA 90040 USA. EM meh1979@gmail.com FU Robert Wood Johnson Foundation Clinical Scholars Program; U.S. Department of Veterans Affairs; National Research Award Program, National Institutes of Health FX We would like to thank the numerous people who helped us with this project including, but not limited to, Ken Wells, MD, MPH; Loretta Jones, MA; the original Martin Luther King, Jr. Community Hospital Board of Directors (Manuel A. Abascal, JD; Elaine Batchlor, MD, MPH; Linda Griego, BA; Paul King, MHA; Michael Madden, MA; Robert Margolis, MD and James Yoshioka, BS); those who graciously allowed us to interview them at Denver Health, Grady Health, Harlem Hospital Center, Mount Sinai Health System, and Virginia Mason Medical Center; and the Robert Wood Johnson Foundation Clinical Scholars Program, the U.S. Department of Veterans Affairs, and the National Research Award Program, National Institutes of Health, for supporting our efforts. NR 23 TC 0 Z9 0 U1 2 U2 6 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 EI 1548-6869 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2016 VL 27 IS 1 BP 293 EP 307 DI 10.1353/hpu.2016.0008 PG 15 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DC9BD UT WOS:000369514400024 PM 27763471 ER PT J AU Peters, AT West, AE Eisner, L Baek, J Deckersbach, T AF Peters, Amy T. West, Amy E. Eisner, Lori Baek, Jihyun Deckersbach, Thilo TI The Burden of Repeated Mood Episodes in Bipolar I Disorder Results From the National Epidemiological Survey on Alcohol and Related Conditions SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Bipolar; depression; functioning ID TREATMENT ENHANCEMENT PROGRAM; STEP-BD; PERSONALITY-DISORDERS; EARLY INTERVENTION; STAGING MODEL; FOLLOW-UP; NEUROPROGRESSION; ILLNESS; PHENOMENOLOGY; RECURRENCE AB The aim of this study was to examine the association between previous mood episodes and clinical course/functioning in a community sample (National Epidemiological Survey on Alcohol and Related Conditions [NESARC]). Subjects (n = 909) met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria for bipolar I disorder and provided data on number of previous episode recurrences. Number of previous mood episodes was used to predict outcomes at wave 1 and wave 2 of the NESARC. Previous mood episodes accounted for small but unique variance in outcomes. Recurrence was associated with poorer functioning, psychiatric and medical comorbidity, and increased odds of suicidality, disability, unemployment, and hospitalization at wave 1. Recurrences were associated with greater risk for new onset suicidality, psychiatric comorbidity, disability, unemployment, and poor functioning by wave 2. The course of bipolar disorder does worsen with progressive mood episodes but is attenuated in community, relative to clinical samples. Interventions to prevent future relapse may be particularly important to implement early in the course of illness. C1 [Peters, Amy T.; West, Amy E.] Univ Illinois, Chicago, IL USA. [Eisner, Lori; Baek, Jihyun; Deckersbach, Thilo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eisner, Lori; Baek, Jihyun; Deckersbach, Thilo] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149-2628,Bldg 149,13th St,2nd Floor, Charlestown, MA 02129 USA. EM tdeckersbach@partners.org FU National Institutes of Mental Health; NARSAD; Tourette Syndrome Association; International OCD Foundation; Tufts University; MGH Psychiatry Academy; BrainCells Inc; Systems Research and Applications Corporation; Boston University; Catalan FX Amy Peters has received funding from the National Institutes of Mental Health. Amy West has received funding from the National Institutes of Mental Health, honoraria from the National Institute of Health (grant review), Northwestern University (Grand Rounds), and University of Lund (academic talk). Thilo Deckersbach has received funding from the National Institutes of Mental Health. Thilo Deckersbach has also received funding from NARSAD, the Tourette Syndrome Association, the International OCD Foundation, and Tufts University. He has received honoraria, consultation fees and/or royalties from the MGH Psychiatry Academy, BrainCells Inc, Systems Research and Applications Corporation, Boston University, the Catalan. NR 38 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD FEB PY 2016 VL 204 IS 2 BP 87 EP 94 DI 10.1097/NMD.0000000000000425 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DD5NP UT WOS:000369971100003 PM 26588078 ER PT J AU Armour, C Contractor, A Shea, T Elhai, JD Pietrzak, RH AF Armour, Cherie Contractor, Ateka Shea, Tracie Elhai, Jon D. Pietrzak, Robert H. TI Factor Structure of the PTSD Checklist for DSM-5 Relationships Among Symptom Clusters, Anger, and Impulsivity SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE PTSD; PCL-5; anger; impulsivity; DSM-5; confirmatory factor analysis ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE DEPENDENT INPATIENTS; CONFIRMATORY FACTOR-ANALYSIS; CLINIC-REFERRED YOUTH; 5 FACTOR MODEL; UNDERLYING DIMENSIONS; EARTHQUAKE SURVIVORS; MALE VETERANS; PSYCHOMETRIC PROPERTIES; EMOTION DYSREGULATION AB Scarce data are available regarding the dimensional structure of Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) posttraumatic stress disorder (PTSD) symptoms and how factors relate to external constructs. We evaluated six competing models of DSM-5 PTSD symptoms, including Anhedonia, Externalizing Behaviors, and Hybrid models, using confirmatory factor analyses in a sample of 412 trauma-exposed college students. We then examined whether PTSD symptom clusters were differentially related to measures of anger and impulsivity using Wald chi-square tests. The seven-factor Hybrid model was deemed optimal compared with the alternatives. All symptom clusters were associated with anger; the strongest association was between externalizing behaviors and anger (r = 0.54). All symptom clusters, except reexperiencing and avoidance, were associated with impulsivity, with the strongest association between externalizing behaviors and impulsivity (r = 0.49). A seven-factor Hybrid model provides superior fit to DSM-5 PTSD symptom data, with the externalizing behaviors factor being most strongly related to anger and impulsivity. C1 [Armour, Cherie] Univ Ulster, Sch Psychol, Coleraine Campus, Coleraine BT52 1SA, Londonderry, North Ireland. [Contractor, Ateka; Elhai, Jon D.] Univ Toledo, Dept Psychol, Toledo, OH USA. [Contractor, Ateka; Shea, Tracie] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Shea, Tracie] Vet Affairs Med Ctr, Providence, RI USA. [Elhai, Jon D.] Univ Toledo, Dept Psychiat, Toledo, OH USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Pietrzak, Robert H.] VA Connecticut Healthcare Syst, Clin Neurosci Div, Natl Ctr Posttraumat Stress Disorder, US Dept Vet Affairs, West Haven, CT USA. RP Armour, C (reprint author), Univ Ulster, Sch Psychol, Coleraine Campus, Coleraine BT52 1SA, Londonderry, North Ireland. EM armour.cherie@gmail.com OI Armour, Cherie/0000-0001-7649-3874 NR 68 TC 2 Z9 2 U1 9 U2 18 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 FEB PY 2016 VL 204 IS 2 BP 108 EP 115 DI 10.1097/NMD.0000000000000430 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DD5NP UT WOS:000369971100006 PM 26669984 ER PT J AU Schofield, CA Dea Moore, C Hall, A Coles, ME AF Schofield, Casey A. Dea Moore, Crystal Hall, Anna Coles, Meredith E. TI Understanding Perceptions of Anxiety Disorders and Their Treatment SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Anxiety; depression; treatment perceptions; mental health literacy ID MENTAL-HEALTH LITERACY; COMORBIDITY SURVEY REPLICATION; SELF-EFFICACY; PSYCHOLOGICAL TREATMENTS; DISSEMINATING TREATMENT; SOCIAL PHOBIA; HELP-SEEKING; YOUNG-PEOPLE; ATTITUDES; BELIEFS AB Characterizing areas of limited knowledge about anxiety disorders and their treatment may help inform treatment dissemination efforts and public health programming. In a sample of 626 adults recruited via Amazon's Mechanical Turk, this study evaluated 1) perceptions of symptoms of anxiety disorders and depression, 2) perceived usefulness of coping approaches (i.e., professional and non-professional help), and 3) awareness of available resources. Results indicated that participants generally recognized that symptoms warranted professional help, and recognition was associated with self-efficacy for seeking mental health care, but not with participants' own symptoms. Furthermore, participants perceived psychotherapy to be the most useful coping approach. Of concern is the perception that symptoms are the result of personal weakness (particularly among male participants and for social anxiety disorder), as well as limited knowledge about publicly available resources. In all, results suggest that there are areas for growth regarding mental health literacy for anxiety disorders. C1 [Schofield, Casey A.; Dea Moore, Crystal] Skidmore Coll, 815 North Broadway, Saratoga Springs, NY 12866 USA. [Hall, Anna] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Coles, Meredith E.] SUNY Binghamton, Binghamton, NY USA. RP Schofield, CA (reprint author), Skidmore Coll, 815 North Broadway, Saratoga Springs, NY 12866 USA. EM cschofie@skidmore.edu NR 41 TC 0 Z9 0 U1 2 U2 7 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 FEB PY 2016 VL 204 IS 2 BP 116 EP 122 DI 10.1097/NMD.0000000000000433 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DD5NP UT WOS:000369971100007 PM 26669982 ER PT J AU Hiar, S Thomas, CL Hinton, DE Salles, J Goutaudier, N Olliac, B Bui, E AF Hiar, Soraya Thomas, Charmaine L. Hinton, Devon E. Salles, Juliette Goutaudier, Nelly Olliac, Bertrand Bui, Eric TI Somatic Symptoms Mediate the Relationship Between Trauma During the Arab Spring and Quality of Life Among Tunisians SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE PTSD; peritraumatic distress; peritraumatic dissociation; cross-cultural validity ID POSTTRAUMATIC STRESS; PTSD; REFUGEES; INVENTORY; ACCIDENT; VALIDITY; VICTIMS AB This study examined the relationship between peritraumatic reactions, posttraumatic stress disorder (PTSD) symptoms, somatic complaints, and quality of life in Tunisians exposed to the events of the Arab Spring. Participants (n = 60) completed an online survey 1 year after the events, assessing peritraumatic distress, peritraumatic dissociation, PTSD symptoms, somatic complaints, and physical and mental quality of life. Results showed that peritraumatic dissociation was independently associated with increased PTSD symptoms and somatic complaints 12 months after the events. Multiple mediator mediation analyses revealed that somatic complaints (not PTSD symptoms) were the only independent mediators of the relationships between peritraumatic dissociation and both physical and mental quality of life. Assessing peritraumatic dissociation soon after trauma exposure among the North African population might help identify individuals at risk for PTSD. Furthermore, the impact of trauma on quality of life may be better explained by somatic complaints than PTSD symptoms among North Africans. C1 [Hiar, Soraya; Thomas, Charmaine L.; Salles, Juliette] Univ Toulouse, Dept Psychiat, Toulouse, France. [Thomas, Charmaine L.] Univ Calgary, Dept Psychol, Calgary, AB T2N 1N4, Canada. [Hinton, Devon E.; Bui, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hinton, Devon E.; Bui, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Goutaudier, Nelly] Univ Toulouse, Dept Psychol, Toulouse, France. [Olliac, Bertrand] Ctr Hosp Esquirol, Dept Psychiat, Limoges, France. [Olliac, Bertrand] INSERM, UMR 1094, Dept Trop Neuroepidemiol, Limoges, France. RP Bui, E (reprint author), Red Sox Fdn & Massachusetts Gen Hosp Home Base Pr, One Bowdoin Sq,6th Floor,Suite 650, Boston, MA 02114 USA.; Bui, E (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Str Disorders, One Bowdoin Sq,6th Floor,Suite 650, Boston, MA 02114 USA. EM tebui@mgh.harvard.edu FU Red Sox Foundation; Massachusetts General Hospital Home Base Program; Highland Street Foundation FX Dr. Bui's research effort was supported by the Red Sox Foundation & Massachusetts General Hospital Home Base Program and the Highland Street Foundation. NR 17 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD FEB PY 2016 VL 204 IS 2 BP 153 EP 155 DI 10.1097/NMD.0000000000000446 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DD5NP UT WOS:000369971100012 PM 26825265 ER PT J AU Chou, R Gordon, DB de Leon-Casasola, OA Rosenberg, JM Bickler, S Brennan, T Carter, T Cassidy, CL Chittenden, EH Degenhardt, E Griffith, S Manworren, R McCarberg, B Montgomery, R Murphy, J Perkal, MF Suresh, S Sluka, K Strassels, S Thirlby, R Viscusi, E Walco, GA Warner, L Weisman, SJ Wu, CL AF Chou, Roger Gordon, Debra B. de Leon-Casasola, Oscar A. Rosenberg, Jack M. Bickler, Stephen Brennan, Tim Carter, Todd Cassidy, Carla L. Chittenden, Eva Hall Degenhardt, Ernest Griffith, Scott Manworren, Renee McCarberg, Bill Montgomery, Robert Murphy, Jamie Perkal, Melissa F. Suresh, Santhanam Sluka, Kathleen Strassels, Scott Thirlby, Richard Viscusi, Eugene Walco, Gary A. Warner, Lisa Weisman, Steven J. Wu, Christopher L. TI Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council SO JOURNAL OF PAIN LA English DT Article DE Postoperative pain management; clinical practice guidelines; analgesia; education; multi-modal therapy; patient assessment; regional analgesia; neuraxial analgesia ID TOTAL KNEE ARTHROPLASTY; CRUCIATE LIGAMENT RECONSTRUCTION; PATIENT-CONTROLLED ANALGESIA; RANDOMIZED CONTROLLED-TRIAL; ELECTRICAL NERVE-STIMULATION; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INTRAARTICULAR BUPIVACAINE INFUSION; PERSISTENT POSTSURGICAL PAIN; LIDOCAINE-PRILOCAINE CREAM; PLACEBO-CONTROLLED TRIAL AB Most patients who undergo surgical procedures experience acute postoperative pain, but evidence suggests that less than half report adequate postoperative pain relief. Many preoperative, intra-operative, and postoperative interventions and management strategies are available for reducing and managing postoperative pain. The American Pain Society, with input from the American Society of Anesthesiologists, commissioned an interdisciplinary expert panel to develop a clinical practice guideline to promote evidence-based, effective, and safer postoperative pain management in children and adults. The guideline was subsequently approved by the American Society for Regional Anesthesia. As part of the guideline development process, a systematic review was commissioned on various aspects related to various interventions and management strategies for postoperative pain. After a review of the evidence, the expert panel formulated recommendations that addressed various aspects of postoperative pain management, including preoperative education, perioperative pain management planning, use of different pharmacological and nonpharmacological modalities, organizational policies, and transition to outpatient care. The recommendations are based on the underlying premise that optimal management begins in the preoperative period with an assessment of the patient and development of a plan of care tailored to the individual and the surgical procedure involved. The panel found that evidence supports the use of multimodal regimens in many situations, although the exact components of effective multi modal care will vary depending on the patient, setting, and surgical procedure. Although these guidelines are based on a systematic review of the evidence on management of postoperative pain, the panel identified numerous research gaps. Of 32 recommendations, 4 were assessed as being supported by high-quality evidence, and 11 (in the areas of patient education and perioperative planning, patient assessment, organizational structures and policies, and transitioning to outpatient care) were made on the basis of low-quality evidence. (C) 2016 by the American Pain Society C1 [Chou, Roger] Oregon Hlth & Sci Univ, Pacific Northwest Evidence Based Practice Ctr, Dept Med, Portland, OR 97201 USA. [Chou, Roger] Oregon Hlth & Sci Univ, Pacific Northwest Evidence Based Practice Ctr, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Gordon, Debra B.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [de Leon-Casasola, Oscar A.] Roswell Pk Canc Inst, Dept Anesthesiol & Pain Med, Buffalo, NY 14263 USA. [de Leon-Casasola, Oscar A.] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Rosenberg, Jack M.] Univ Michigan, Vet Integrated Serv Network, Dept Vet Affairs, Ann Arbor, MI 48109 USA. [Rosenberg, Jack M.] Univ Michigan, Dept Phys Med, Ann Arbor, MI 48109 USA. [Rosenberg, Jack M.] Univ Michigan, Dept Rehabil & Anesthesiol, Ann Arbor, MI 48109 USA. [Bickler, Stephen] Univ Calif San Diego, Pediat Surg, San Diego, CA 92103 USA. [Brennan, Tim] Univ Iowa Hosp & Clin, Dept Anesthesia, Iowa City, IA 52242 USA. [Carter, Todd] Univ Cincinnati, Dept Anesthesia, Cincinnati, OH USA. [Cassidy, Carla L.] Vet Hlth Adm, Dept Vet Affairs, Washington, DC USA. [Chittenden, Eva Hall] Massachusetts Gen Hosp, Dept Palliat Care, Boston, MA 02114 USA. [Degenhardt, Ernest] United States Army Med Command, Qual Management Div, San Antonio, TX USA. [Griffith, Scott] Walter Reed Army Med Ctr, Crit Care Med, Bethesda, MD USA. [Manworren, Renee] Univ Connecticut, Sch Med, Dept Pediat, Mansfield, CT USA. [McCarberg, Bill] Amer Acad Pain Med, San Diego, CA USA. [Montgomery, Robert] Univ Colorado, Dept Anesthesiol, Denver, CO 80202 USA. [Murphy, Jamie; Wu, Christopher L.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Perkal, Melissa F.] Vet Affairs Med Ctr, Dept Surg, West Haven, CT USA. [Suresh, Santhanam] Childrens Hosp Chicago, Dept Pediat Anesthesia, Chicago, IL USA. [Sluka, Kathleen] Univ Iowa, Dept Phys Therapy & Rehabil, Iowa City, IA USA. [Strassels, Scott] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Thirlby, Richard] Virginia Mason Med Ctr, Bariatr Weight Loss Surg Ctr, Seattle, WA 98101 USA. [Viscusi, Eugene] Thomas Jefferson Univ, Dept Anesthesiol, Philadelphia, PA 19107 USA. [Walco, Gary A.] Seattle Childrens Hosp, Dept Anesthesiol & Pain Med, Seattle, WA USA. [Warner, Lisa] Dept Veteran Affairs, Phoenix, AZ USA. [Weisman, Steven J.] Childrens Hosp Wisconsin, Dept Anesthesiol, Wauwatosa, WI USA. RP Chou, R (reprint author), 3181 SW Sam Jackson Pk Rd,Mail Code BICC, Portland, OR 97239 USA. EM chour@ohsu.edu FU American Pain Society FX Funding for this guideline was provided by the American Pain Society. The guideline was submitted for approval by the partnering organizations, but the content of the guideline is the sole responsibility of the authors and panel members. NR 320 TC 36 Z9 42 U1 11 U2 27 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD FEB PY 2016 VL 17 IS 2 BP 131 EP 157 DI 10.1016/j.jpain.2015.12.008 PG 27 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DD7NO UT WOS:000370111600001 PM 26827847 ER PT J AU Barolet, D Christiaens, F Hamblin, MR AF Barolet, Daniel Christiaens, Francois Hamblin, Michael R. TI Infrared and skin: Friend or foe SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE Infrared (IR); IR-A; Photobiomodulation; MMP-1; Photoprevention; Irradiance ID HUMAN DERMAL FIBROBLASTS; BIPHASIC DOSE-RESPONSE; LEVEL LIGHT THERAPY; PHOTODYNAMIC THERAPY; CELLULAR-RESPONSE; SUN PROTECTION; HAIRLESS MICE; EXPOSURE TIME; SHADOW RULE; IN-VIVO AB In the last decade, it has been proposed that the sun's IR-A wavelengths might be deleterious to human skin and that sunscreens, in addition to their desired effect to protect against UV-B and UV-A, should also protect against IR-A (and perhaps even visible light). Several studies showed that NIR may damage skin collagen content via an increase in MMP-1 activity in the same manner as is known for UVR. Unfortunately, the artificial NIR light sources used in such studies were not representative of the solar irradiance. Yet, little has been said about the other side of the coin. This article will focus on key information suggesting that IR-A may be more beneficial than deleterious when the skin is exposed to the appropriate irradiance/dose of IR-A radiation similar to daily sun exposure received by people in real life. IR-A might even precondition the skin a process called photoprevention from an evolutionary standpoint since exposure to early morning IR-A wavelengths in sunlight may ready the skin for the coming mid-day deleterious UVR. Consequently IR-A appears to be the solution, not the problem. It does more good than bad for the skin. It is essentially a question of intensity and how we can learn from the sun. (C) 2016 The Authors. Published by Elsevier B.V. C1 [Barolet, Daniel] McGill Univ, Dept Med, Div Dermatol, Montreal, PQ H3A 1A1, Canada. [Barolet, Daniel] RoseLab Skin Opt Lab, Laval, PQ H7T 0G3, Canada. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Barolet, D (reprint author), RoseLab Skin Opt Lab, Div Dermatol, 3333 100th Ave,Suite 200, Laval, PQ H7T 0G3, Canada. EM daniel.barolet@mcgill.ca FU US NIH [R01AI050875] FX DB & FC have no conflicts of interest. MRH was supported by US NIH grant R01AI050875. NR 64 TC 8 Z9 8 U1 5 U2 17 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD FEB PY 2016 VL 155 BP 78 EP 85 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DD7GC UT WOS:000370090700011 PM 26745730 ER PT J AU Augustine, MB Swift, KM Harris, SR Anderson, EJ Hand, RK AF Augustine, Mary Beth Swift, Kathie M. Harris, Stephanie R. Anderson, Ellen J. Hand, Rosa K. TI Integrative Medicine: Education, Perceived Knowledge, Attitudes, and Practice among Academy of Nutrition and Dietetics Members SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Editorial Material ID REGISTERED DIETITIANS; ALTERNATIVE MEDICINE; DIETARY-SUPPLEMENTS; FUNCTIONAL FOODS; COMPLEMENTARY; COMPETENCES; PROGRAMS; POSITION C1 [Augustine, Mary Beth; Swift, Kathie M.; Harris, Stephanie R.] Acad Nutr & Dietet, Integrat & Funct Med Dietet Practice Grp, Chicago, IL USA. [Augustine, Mary Beth] Mt Sinai Beth Israel, New York, NY USA. [Swift, Kathie M.] Integrat & Funct Nutr Acad, Palm Harbor, FL USA. [Harris, Stephanie R.] Case Western Reserve Univ, Dept Nutr, Cleveland, OH 44106 USA. [Anderson, Ellen J.] Acad Nutr & Dietet, Dietet Practice Based Res Network Oversight Comm, Chicago, IL USA. [Anderson, Ellen J.] Massachusetts Gen Hosp, Metab & Nutr Res, Boston, MA 02114 USA. [Hand, Rosa K.] Acad Nutr & Dietet, Dietet Practice Based Res Network, 120 S Riverside Plaza,Suite 2000, Chicago, IL 60606 USA. RP Hand, RK (reprint author), Acad Nutr & Dietet, Dietet Practice Based Res Network, 120 S Riverside Plaza,Suite 2000, Chicago, IL 60606 USA. EM rhand@eatright.org NR 22 TC 0 Z9 0 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 EI 2212-2680 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD FEB PY 2016 VL 116 IS 2 BP 319 EP 329 DI 10.1016/j.jand.2015.08.015 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DD0KH UT WOS:000369608400016 PM 26387076 ER PT J AU Harvey, HB Tomov, E Babayan, A Dwyer, K Boland, S Pandharipande, PV Halpern, EF Alkasab, TK Hirsch, JA Schaefer, PW Boland, GW Choy, G AF Harvey, H. Benjamin Tomov, Elena Babayan, Astrid Dwyer, Kathy Boland, Sam Pandharipande, Pari V. Halpern, Elkan F. Alkasab, Tarik K. Hirsch, Joshua A. Schaefer, Pamela W. Boland, Giles W. Choy, Garry TI Radiology Malpractice Claims in the United States From 2008 to 2012: Characteristics and Implications SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Radiology; medical malpractice; malpractice; liability; damages; policy; regulation; law ID DIGITAL BREAST TOMOSYNTHESIS; COMPUTER-AIDED DETECTION; MEDICAL-MALPRACTICE; CLINICAL INFORMATION; SCREENING MAMMOGRAPHY; ACCURACY; LITIGATION; CANCER; SUITS; PERFORMANCE AB Purpose: The aim of this study was to compare the frequency and liability costs associated with radiology malpractice claims relative to other medical services and to evaluate the clinical context and case disposition associated with radiology malpractice claims. Methods: This HIPAA-compliant study was exempted from institutional review board approval. The Comparative Benchmarking System database, a repository of more than 300,000 medical malpractice cases in the United States, was queried for closed claims over a five-year period (2008-2012). Claims were categorized by the medical service primarily responsible for the claim and the paid total loss. For all cases in which radiology was the primary responsible service, the case abstracts were evaluated to determine injury severity, claimant type by setting, claim allegation, process of care involved, case disposition, modality involved, and body section. Intracategory comparisons were made on the basis of the frequency of indemnity payment and total indemnity payment for paid cases, using chi(2) and Wilcoxon rank-sum tests. Results: Radiology was the eighth most likely responsible service to be implicated in a medical malpractice claim, with a median total paid loss (indemnity payment plus defense cost plus administrative expense) per closed case of $30,091 (mean, $205,619 +/- $508,883). Radiology claims were most commonly associated with high- and medium-severity injuries (93.3% [820 of 879]; 95% confidence interval [CI], 91.7%-94.95%), the outpatient setting (66.3% [581 of 876]; 95% CI, 63.0%-69.2%), and diagnosis-related allegations (ie, failure to diagnose or delayed diagnosis) (57.3% [504 of 879]; 95% CI, 54.0%-60.6%). A high proportion of claims pertained to cancer diagnoses (44.0% [222 of 504]; 95% CI, 39.7%-48.3%). A total of 62.3% (548 of 879; 95% CI, 59.1%-65.5%) of radiology claims were closed without indemnity payments; 37.7% (331 of 879; 95% CI, 34.5%-40.9%) were closed with a median indemnity payment of $175,000 (range, $112-$6,691,762; mean $481,094 +/- $727,636). Conclusions: Radiology malpractice claims most commonly involve diagnosis-related allegations in the outpatient setting, particularly cancer diagnoses, with approximately one-third of claims resulting in payouts to the claimants. C1 [Harvey, H. Benjamin; Boland, Sam; Pandharipande, Pari V.; Alkasab, Tarik K.; Hirsch, Joshua A.; Schaefer, Pamela W.; Boland, Giles W.; Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, 39 Melrose St,Unit 2, Boston, MA USA. [Harvey, H. Benjamin; Pandharipande, Pari V.; Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Harvey, H. Benjamin; Pandharipande, Pari V.; Halpern, Elkan F.; Alkasab, Tarik K.; Hirsch, Joshua A.; Schaefer, Pamela W.; Boland, Giles W.; Choy, Garry] Harvard Univ, Sch Med, Boston, MA USA. [Tomov, Elena; Babayan, Astrid; Dwyer, Kathy] CRICO Risk Management Fdn, Cambridge, MA USA. RP Harvey, HB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 39 Melrose St,Unit 2, Boston, MA USA. EM hbharvey@partners.org OI Boland, Samuel/0000-0001-6470-5470; Tomov, Elena/0000-0002-7972-3222 FU Medtronic; Carefusion; Medical Imaging and Technology Alliance FX Ms. Tomov, Dr. Babayan, and Ms. Dwyer are employees of CRICO Risk Management Foundation, which provided professional liability insurance for some of the analyzed claims; Dr. Hirsch reports personal fees from Medtronic and Carefusion and Dr. Pandharipande reports grants from Medical Imaging and Technology Alliance, outside the submitted work. NR 36 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD FEB PY 2016 VL 13 IS 2 BP 124 EP 130 DI 10.1016/j.jacr.2015.07.013 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD4FL UT WOS:000369877800009 PM 26454772 ER PT J AU Murphey, MD Roberts, CC Bencardino, JT Appel, M Arnold, E Chang, EY Dempsey, ME Fox, MG Fries, IB Greenspan, BS Hochman, MG Jacobson, JA Mintz, DN Newman, JS Rosenberg, ZS Rubin, DA Small, KM Weissman, BN AF Murphey, Mark D. Roberts, Catherine C. Bencardino, Jenny T. Appel, Marc Arnold, Erin Chang, Eric Y. Dempsey, Molly E. Fox, Michael G. Fries, Ian Blair Greenspan, Bennett S. Hochman, Mary G. Jacobson, Jon A. Mintz, Douglas N. Newman, Joel S. Rosenberg, Zehava S. Rubin, David A. Small, Kirstin M. Weissman, Barbara N. TI ACR Appropriateness Criteria Osteonecrosis of the Hip SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness criteria; osteonecrosis; adult; child; MRI; radiograph ID CALVE-PERTHES-DISEASE; FEMORAL-HEAD OSTEONECROSIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; SUBCHONDRAL INSUFFICIENCY FRACTURE; CONTRAST-ENHANCED MRI; SICKLE-CELL-DISEASE; BONE-MARROW EDEMA; AVASCULAR NECROSIS; ASYMPTOMATIC OSTEONECROSIS; CORE DECOMPRESSION AB Osteonecrosis of the hip (Legg-Calve-Perthes) is a common disease, with 10,000-20,000 symptomatic cases annually in the United States. The disorder affects both adults and children and is most frequently associated with trauma and corticosteroid usage. The initial imaging evaluation of suspected hip osteonecrosis is done using radiography. MRI is the most sensitive and specific imaging modality for diagnosis of osteonecrosis of the hip. The clinical significance of hip osteonecrosis is dependent on its potential for articular collapse. The likelihood of articular collapse is significantly increased with involvement of greater than 30%-50% of the femoral head area, which is optimally evaluated by MRI, often in the sagittal plane. Contrast-enhanced MRI may be needed to detect early osteonecrosis of the hip in pediatric patients, revealing hypoperfusion. In patients with a contraindication for MRI, use of either CT or bone scintigraphy with SPECT (single-photon emission CT) are alternative radiologic methods of assessment. Imaging helps guide treatment, which may include core decompression, osteotomy, and ultimately, need for joint replacement. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Murphey, Mark D.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Roberts, Catherine C.] Mayo Clin, Phoenix, AZ USA. [Bencardino, Jenny T.] NYU Radiol Associates, New York, NY USA. [Appel, Marc] Amer Acad Orthopaed Surgeons, James J Peters VA Med Ctr, Bronx, NY USA. [Arnold, Erin] Amer Coll Rheumatol, Orthopaed & Rheumatol North Shore, Skokie, IL USA. [Chang, Eric Y.] VA San Diego Healthcare Syst, San Diego, CA USA. [Dempsey, Molly E.] Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA. [Fox, Michael G.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Fries, Ian Blair] Amer Acad Orthopaed Surgeons, Bone Spine & Hand Surg, Chartered, Brick, NJ USA. [Greenspan, Bennett S.] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA. [Hochman, Mary G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Jacobson, Jon A.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Mintz, Douglas N.] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. [Newman, Joel S.] New England Baptist Hosp, Boston, MA USA. [Rosenberg, Zehava S.] Hosp Joint Dis & Med Ctr, New York, NY USA. [Rubin, David A.] Washington Univ, Sch Med, St Louis, MO USA. [Small, Kirstin M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Murphey, MD (reprint author), 1010 Wayne Ave Ste 320, Silver Spring, MD 20910 USA. EM mmurphey@acr.org OI Jacobson, Jon/0000-0002-3676-6628; Rosenberg MD, Zehava/0000-0003-1902-6350 NR 68 TC 1 Z9 1 U1 1 U2 4 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 FEB PY 2016 VL 13 IS 2 BP 147 EP 155 DI 10.1016/j.jacr.2015.10.033 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD4FL UT WOS:000369877800014 PM 26846390 ER PT J AU Lu, MT Rosman, DA Wu, CC Gilman, MD Harvey, HB Gervais, DA Alkasab, TK Shepard, JAO Boland, GW Pandharipande, PV AF Lu, Michael T. Rosman, David A. Wu, Carol C. Gilman, Matthew D. Harvey, H. Benjamin Gervais, Debra A. Alkasab, Tarik K. Shepard, Jo-Anne O. Boland, Giles W. Pandharipande, Pari V. TI Radiologist Point-of-Care Clinical Decision Support and Adherence to Guidelines for Incidental Lung Nodules SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Clinical decision support; lung nodule ID FLEISCHNER SOCIETY GUIDELINES; PULMONARY NODULES; FINDINGS COMMITTEE; SCREENING TRIAL; ABDOMINAL CT; WHITE PAPER; ORDER-ENTRY; MANAGEMENT; QUALITY; APPROPRIATENESS AB Purpose: To evaluate the effect of a workstation-integrated, point-of-care, clinical decision support (CDS) tool on radiologist adherence to radiology department guidelines for follow-up of incidental pulmonary nodules detected on abdominal CT. Methods: The CDS tool was developed to facilitate adherence to department guidelines for managing pulmonary nodules seen on abdominal CT. In October 2012, the tool was deployed within the radiology department of an academic medical center and could be used for a given abdominal CT at the discretion of the interpreting radiologist. We retrospectively identified consecutive patients who underwent abdominal CT (in the period from January 2012 to April 2013), had no comparison CT scans available, and were reported to have a solid, noncalcified, pulmonary nodule. Concordance between radiologist follow-up recommendation and department guidelines was compared among three groups: patients scanned before implementation of the CDS tool; and patients scanned after implementation, with versus without use of the tool. Results: A total of 409 patients were identified, including 268 for the control group. Overall, guideline concordance was higher after CDS tool implementation (92 of 141 [65%] versus 133 of 268 [50%], P=.003). This finding was driven by the subset of post-CDS implementation cases in which the CDS tool was used (57 of 141 [40%]). In these cases, guideline concordance was significantly higher (54 of 57 [95%]), compared with post-implementation cases in which CDS was not used (38 of 84 [45%], P<.001), and to a control group of patients from before implementation (133 of 268 [50%]; P<.001). Conclusions: A point-of-care CDS tool was associated with improved adherence to guidelines for follow-up of incidental pulmonary nodules. C1 [Lu, Michael T.] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lu, MT (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mlu@mgh.harvard.edu FU Harvey L. Neiman Health Policy Institute(R); American Roentgen Ray Society FX MTL reports research grant support from the Harvey L. Neiman Health Policy Institute (R) and the American Roentgen Ray Society. NR 32 TC 3 Z9 3 U1 1 U2 3 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 FEB PY 2016 VL 13 IS 2 BP 156 EP 162 DI 10.1016/j.jacr.2015.09.029 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD4FL UT WOS:000369877800015 PM 26577875 ER PT J AU Boland, GW Duszak, R AF Boland, Giles W. Duszak, Richard, Jr. TI A Roadmap for Value-Based Payments SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Boland, Giles W.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 32 Fruit St, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. RP Boland, GW (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 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 3 TC 3 Z9 3 U1 1 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 FEB PY 2016 VL 13 IS 2 BP 170 EP 172 DI 10.1016/j.jacr.2015.10.003 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD4FL UT WOS:000369877800017 PM 26777737 ER PT J AU Golden, DW Braunstein, S Jimenez, RB Mohindra, P Spektor, A Ye, JC Bradley, KA Chmura, SJ Currey, A Das, P Du, K Haas-Kogan, D Howard, AR Higgins, SA Hung, AY Kharofa, J Krishnan, MS MacDonald, SM Mancini, BR Parashar, B Thaker, NG Thomas, CR Viswanathan, AN Wheatley, M AF Golden, Daniel W. Braunstein, Steve Jimenez, Rachel B. Mohindra, Pranshu Spektor, Alexander Ye, Jason C. Bradley, Kristin A. Chmura, Steven J. Currey, Adam Das, Prajnan Du, Kevin Haas-Kogan, Daphne Howard, Andrew R. Higgins, Susan A. Hung, Arthur Y. Kharofa, Jordan Krishnan, Monica S. MacDonald, Shannon M. Mancini, Brandon R. Parashar, Bhupesh Thaker, Nikhil G. Thomas, Charles R., Jr. Viswanathan, Akila N. Wheatley, Matt CA Radiation Oncology Educ Radiation Oncology Educ TI Multi-Institutional Implementation and Evaluation of a Curriculum for the Medical Student Clerkship in Radiation Oncology SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Radiation oncology; undergraduate medical education; curriculum; medical students ID EDUCATION; KNOWLEDGE; INCREASE; TRIAL AB Purpose: Radiation oncology curriculum development is challenging because of limited numbers of trainees at any single institution. The goal of this project is to implement and evaluate a standardized medical student clerkship curriculum following the multi institutional cooperative group research model. Methods: During the 2013 academic year, a standardized curriculum was implemented at 11 academic medical centers consisting of three 1-hour lectures and a hands-on radiation treatment planning workshop. After the curriculum, students completed anonymous evaluations using Likert-type scales (1 = "not at all" to 5 = "extremely') and free responses. Evaluations asked students to rate their comfort, before and after the curriculum, with radiation oncology as a specialty, knowledge of radiotherapy planning methods, and ability to function as a radiation oncology resident. Nonparametric statistical tests were used in the analysis. Results: Eighty-eight students at 11 academic medical centers completed the curriculum de novo, with a 72.7% (64 of 88) survey response rate. Fifty-seven students (89.1%) reported intent to pursue radiation oncology as their specialty. Median (interquartile range) student ratings of the importance of curricular content were as follows: overview, 4 (4-5); radiation biology/physics, 5 (4-5); practical aspects/emergencies, 5 (4-5); and planning workshop, 4 (4-5). Students reported that the curriculum helped them better understand radiation oncology as a specialty (5 [4-5]), increased specialty decision comfort (4 [3-5]), and would help the transition to radiation oncology residency (4 [4-5]). Students rated their specialty decision comfort significantly higher after completing the curriculum (4 [4-5] versus 5 [5-5]; P < .001). Conclusions: A national standardized curriculum was successfully implemented at 11 academic medical centers, providing proof of principle that curriculum development can follow the multi-institutional cooperative group research model. C1 [Golden, Daniel W.; Chmura, Steven J.; Howard, Andrew R.] Univ Chicago, Pritzker Sch Med, Dept Radiat & Cellular Oncol, 5758 South Maryland Ave,Mail Code 9006, Chicago, IL 60637 USA. [Braunstein, Steve] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Jimenez, Rachel B.; MacDonald, Shannon M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Mohindra, Pranshu] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA. [Spektor, Alexander; Haas-Kogan, Daphne; Krishnan, Monica S.; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Spektor, Alexander; Haas-Kogan, Daphne; Krishnan, Monica S.; Viswanathan, Akila N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Ye, Jason C.; Parashar, Bhupesh] New York Presbyterian Hosp, Weill Cornell Med Coll, Weill Cornell Med Ctr, Dept Radiat Oncol,Stich Radiat Oncol Ctr, New York, NY USA. [Das, Prajnan; Thaker, Nikhil G.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Higgins, Susan A.; Mancini, Brandon R.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Bradley, Kristin A.] Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Madison, WI USA. [Hung, Arthur Y.; Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Dept Radiat Med, Knight Canc Inst, Portland, OR 97201 USA. [Kharofa, Jordan] Univ Cincinnati, Dept Radiat Oncol, Cincinnati, OH USA. [Currey, Adam; Wheatley, Matt] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Du, Kevin] NYU, Dept Radiat Oncol, Perlmutter Canc Ctr, New York, NY USA. RP Golden, DW (reprint author), Univ Chicago, Pritzker Sch Med, Dept Radiat & Cellular Oncol, 5758 South Maryland Ave,Mail Code 9006, Chicago, IL 60637 USA. EM dgolden@radonc.uchicago.edu FU Philips Healthcare/RSNA Education Scholar Grant; National Institutes of Health Clinical Translational Science Awar [UL1 RR024999]; RSNA; RadOnc Questions, LLC FX This project was funded in part by the 2013 Philips Healthcare/RSNA Education Scholar Grant and National Institutes of Health Clinical Translational Science Award UL1 RR024999.; Dr Golden has received grants from the RSNA and has a financial interest in RadOnc Questions, LLC. The other authors have no conflicts of interest related to the material discussed in this article. NR 21 TC 3 Z9 3 U1 1 U2 4 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 FEB PY 2016 VL 13 IS 2 BP 203 EP 209 DI 10.1016/j.jacr.2015.06.036 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD4FL UT WOS:000369877800026 ER PT J AU Misono, AS Prabhakar, AM Liu, RW Shetty, SK AF Misono, Alexander S. Prabhakar, Anand M. Liu, Raymond W. Shetty, Sanjay K. TI What Radiology Can Learn From the Management Consulting Industry SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Misono, Alexander S.; Prabhakar, Anand M.; Liu, Raymond W.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shetty, Sanjay K.] Steward Hlth Care Network, Boston, MA USA. [Shetty, Sanjay K.] St Elizabeths Med Ctr, Dept Radiol, Boston, MA USA. RP Misono, AS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders 216, Boston, MA 02114 USA. EM amisono@mgh.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD FEB PY 2016 VL 13 IS 2 BP 222 EP 225 DI 10.1016/j.jacr.2015.09.023 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD4FL UT WOS:000369877800029 PM 26846394 ER PT J AU Daly, MB Pilarski, R Axilbund, JE Berry, M Buys, SS Crawford, B Farmer, M Friedman, S Garber, JE Khan, S Klein, C Kohlmann, W Kurian, A Litton, JK Madlensky, L Marcom, PK Merajver, SD Offit, K Pal, T Rana, H Reiser, G Robson, ME Shannon, KM Swisher, E Voian, NC Weitzel, JN Whelan, A Wick, MJ Wiesner, GL Dwyer, M Kumar, R Darlow, S AF Daly, Mary B. Pilarski, Robert Axilbund, Jennifer E. Berry, Michael Buys, Saundra S. Crawford, Beth Farmer, Meagan Friedman, Susan Garber, Judy E. Khan, Seema Klein, Catherine Kohlmann, Wendy Kurian, Allison Litton, Jennifer K. Madlensky, Lisa Marcom, P. Kelly Merajver, Sofia D. Offit, Kenneth Pal, Tuya Rana, Huma Reiser, Gwen Robson, Mark E. Shannon, Kristen Mahoney Swisher, Elizabeth Voian, Nicoleta C. Weitzel, Jeffrey N. Whelan, Alison Wick, Myra J. Wiesner, Georgia L. Dwyer, Mary Kumar, Rashmi Darlow, Susan TI Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2015 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID PEUTZ-JEGHERS-SYNDROME; SEX CORD TUMOR; BRCA2 GERMLINE MUTATIONS; CANCER-RISK; PANCREATIC-CANCER; ANNULAR TUBULES; PATHOLOGICAL FINDINGS; CARCINOMA; ADENOCARCINOMA; PREVALENCE AB The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling and risk assessment and management for hereditary cancer syndromes. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meeting. Major discussion topics this year included multigene testing, risk management recommendations for less common genetic mutations, and salpingectomy for ovarian cancer risk reduction. The panel also discussed revisions to genetic testing criteria that take into account ovarian cancer histology and personal history of pancreatic cancer. C1 [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Pilarski, Robert] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Pilarski, Robert] Solove Res Inst, Columbus, OH USA. [Axilbund, Jennifer E.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Berry, Michael] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Buys, Saundra S.; Kohlmann, Wendy] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Crawford, Beth] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Farmer, Meagan] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Friedman, Susan] FORCE Facing Our Risk Canc Empowered, San Francisco, CA USA. [Garber, Judy E.; Rana, Huma] Dana Farber Brigham & Womens Canc Ctr, New York, NY USA. [Khan, Seema] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Klein, Catherine] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Kurian, Allison] Stanford Canc Inst, Stanford, CA USA. [Litton, Jennifer K.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Madlensky, Lisa] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Marcom, P. Kelly] Duke Canc Inst, Durham, NC USA. [Marcom, P. Kelly] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Offit, Kenneth; Robson, Mark E.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Pal, Tuya] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Reiser, Gwen] Fred & Pamela Buffett Canc Ctr, Lincoln, NE USA. [Shannon, Kristen Mahoney] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Weitzel, Jeffrey N.] Univ Washington, Med Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Voian, Nicoleta C.] Roswell Pk Canc Inst, Buffalo, NY USA. [Weitzel, Jeffrey N.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Whelan, Alison] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Whelan, Alison] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Wick, Myra J.] Mayo Clin, Ctr Canc, Rochester, MI USA. [Wiesner, Georgia L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Dwyer, Mary; Kumar, Rashmi; Darlow, Susan] Natl Comprehens Canc Network, New York, NY USA. RP Daly, MB (reprint author), Fox Chase Canc Ctr, Philadelphia, PA USA. OI Rana, Huma/0000-0002-1598-6752 FU AstraZeneca; Bayer Healthcare Pharmaceuticals Inc.; Bristol-Myers Squibb; Clovis Oncology; Genentech; Novartis Oncology; Otsuka America Pharmaceutical, Inc.; Seattle Genetics, Inc.; Takeda Oncology; Actelion Pharmaceuticals US, Inc.; Astellas; Medivation, Inc. FX This activity is supported by educational grants from AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Clovis Oncology, Genentech, Novartis Oncology, Otsuka America Pharmaceutical, Inc., Seattle Genetics, Inc., and Takeda Oncology; support provided by Actelion Pharmaceuticals US, Inc.; and by an independent educational grant from Astellas and Medivation, Inc. NR 46 TC 17 Z9 17 U1 0 U2 4 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 FEB PY 2016 VL 14 IS 2 BP 153 EP 162 PG 10 WC Oncology SC Oncology GA DD0UA UT WOS:000369634300006 PM 26850485 ER PT J AU Zelenetz, AD Gordon, LI Wierda, WG Abramson, JS Advani, RH Andreadis, CB Bartlett, N Byrd, JC Fayad, LE Fisher, RI Glenn, MJ Habermann, TM Harris, NL Hernandez-Ilizaliturri, F Hoppe, RT Horwitz, SM Kaminski, MS Kelsey, CR Kim, YH Krivacic, S LaCasce, AS Lunning, M Nademanee, A Porcu, P Press, O Rabinovitch, R Reddy, N Reid, E Roberts, K Saad, AA Sokol, L Swinnen, LJ Vose, JM Yahalom, J Zafar, N Dwyer, M Sundar, H AF Zelenetz, Andrew D. Gordon, Leo I. Wierda, William G. Abramson, Jeremy S. Advani, Ranjana H. Andreadis, C. Babis Bartlett, Nancy Byrd, John C. Fayad, Luis E. Fisher, Richard I. Glenn, Martha J. Habermann, Thomas M. Harris, Nancy Lee Hernandez-Ilizaliturri, Francisco Hoppe, Richard T. Horwitz, Steven M. Kaminski, Mark S. Kelsey, Christopher R. Kim, Youn H. Krivacic, Susan LaCasce, Ann S. Lunning, Matthew Nademanee, Auayporn Porcu, Pierluigi Press, Oliver Rabinovitch, Rachel Reddy, Nishitha Reid, Erin Roberts, Kenneth Saad, Ayman A. Sokol, Lubomir Swinnen, Lode J. Vose, Julie M. Yahalom, Joachim Zafar, Nadeem Dwyer, Mary Sundar, Hema TI Diffuse Large B-Cell Lymphoma Version 1.2016 Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID NON-HODGKINS-LYMPHOMA; POSITRON-EMISSION-TOMOGRAPHY; INVOLVED-FIELD RADIOTHERAPY; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; DETUDE-DES-LYMPHOMES; GRAY-ZONE LYMPHOMA; HIGH-DOSE THERAPY; NERVOUS-SYSTEM PROPHYLAXIS; CHOP-LIKE CHEMOTHERAPY; SINGLE-INSTITUTION EXPERIENCE AB Diffuse large B-cell lymphomas (DLBCL) are now considered a heterogeneous group of distinct molecular subtypes (germinal center B-cell DLBCL, activated B-cell DLBCL, and primary mediastinal large B-cell lymphoma (PMBL) with varied natural history and response to therapy. In addition, a subset of patients with DLBCL have concurrent MYC and/or BCL2 gene rearrangements (double-hit lymphomas; DHL) and others have a dual expression of both MYC and BCL2 proteins (double-expressing DLBCL; DEL). The standard of care for the treatment of patients with PMBL, DHL, or DEL has not been established. Adequate immunophenotyping and molecular testing (in selected circumstances) are necessary for the accurate diagnosis of different subtypes of DLBCL. The NCCN Guidelines included in this issue, part of the NCCN Guidelines for non-Hodgkin's lymphomas, address the diagnosis and management of DLBCL and its subtypes. C1 [Zelenetz, Andrew D.; Horwitz, Steven M.] Mem Sloan Kettering Canc Ctr, Med Oncol, New York, NY 10065 USA. [Zelenetz, Andrew D.; Horwitz, Steven M.] Mem Sloan Kettering Canc Ctr, Internal Med, New York, NY 10025 USA. [Gordon, Leo I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Hematol Hematol Oncol, Evanston, IL 60208 USA. [Gordon, Leo I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Bone Marrow Transplantat, Evanston, IL 60208 USA. [Wierda, William G.; Fayad, Luis E.] Univ Texas MD Anderson Canc Ctr, Med Oncol, Houston, TX USA. [Wierda, William G.; Fayad, Luis E.] Univ Texas MD Anderson Canc Ctr, Hematol Hematol Oncol, Houston, TX USA. [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Med Oncol, Boston, MA 02114 USA. [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Hematol Hematol Oncol, Boston, MA 02114 USA. [Advani, Ranjana H.; Kim, Youn H.] Stanford Canc Inst, Med Oncol, Stanford, CA USA. [Andreadis, C. Babis] UCSF Helen Diller Family Comprehens Canc Ctr, Hematol Hematol Oncol, San Francisco, CA USA. [Andreadis, C. Babis] UCSF Helen Diller Family Comprehens Canc Ctr, Med Oncol, San Francisco, CA USA. [Bartlett, Nancy] Barnes Jewish Hosp, Siteman Canc Ctr, Med Oncol, Washington, DC USA. [Bartlett, Nancy] Washington Univ, Sch Med, Med Oncol, St Louis, MO 63130 USA. [Byrd, John C.; Porcu, Pierluigi] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Hematol Hematol Oncol, Columbus, OH 43210 USA. [Byrd, John C.; Porcu, Pierluigi] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Internal Med, Columbus, OH 43210 USA. [Byrd, John C.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Bone Marrow Transplantat, Columbus, OH 43210 USA. [Byrd, John C.; Porcu, Pierluigi] Solove Res Inst, Hematol Hematol Oncol, Columbus, OH USA. [Byrd, John C.; Porcu, Pierluigi] Solove Res Inst, Internal Med, Columbus, OH USA. [Byrd, John C.] Solove Res Inst, Bone Marrow Transplantat, Columbus, OH USA. [Fayad, Luis E.] Univ Texas MD Anderson Canc Ctr, Internal Med, Houston, TX USA. [Fisher, Richard I.] Fox Chase Canc Ctr, Hematol Hematol Oncol, Philadelphia, PA USA. [Fisher, Richard I.] Fox Chase Canc Ctr, Med Oncol, Philadelphia, PA USA. [Glenn, Martha J.] Univ Utah, Huntsman Canc Inst, Med Oncol, Salt Lake City, UT 84112 USA. [Glenn, Martha J.] Univ Utah, Huntsman Canc Inst, Hematol Hematol Oncol, Salt Lake City, UT 84112 USA. [Glenn, Martha J.] Univ Utah, Huntsman Canc Inst, Bone Marrow Transplantat, Salt Lake City, UT 84112 USA. [Harris, Nancy Lee] Mayo Clin, Ctr Canc, Hematol Hematol Oncol, Rochester, MN USA. [Harris, Nancy Lee] Mayo Clin, Ctr Canc, Bone Marrow Transplantat, Rochester, MI USA. [Harris, Nancy Lee] Massachusetts Gen Hosp, Ctr Canc, Pathol, Boston, MA 02114 USA. [Hernandez-Ilizaliturri, Francisco] Roswell Pk Canc Inst, Med Oncol, Buffalo, NY USA. [Hoppe, Richard T.] Stanford Canc Inst, Radiotherapy Radiat Oncol, Stanford, CA USA. [Kaminski, Mark S.] Univ Michigan, Ctr Comprehens Canc, Med Oncol, Ann Arbor, MI 48109 USA. [Kelsey, Christopher R.] Duke Canc Inst, Radiotherapy Radiat Oncol, Durham, NC USA. [Kim, Youn H.] Stanford Canc Inst, Dermatol, Stanford, CA USA. [LaCasce, Ann S.] Dana Farber Brigham & Womens Canc Ctr, Med Oncol, Boston, MA USA. [Lunning, Matthew] Fred & Pamela Buffett Canc Ctr, Internal Med, New York, NY USA. [Nademanee, Auayporn] City Hope Comprehens Canc Ctr, Med Oncol, Duarte, CA USA. [Nademanee, Auayporn] City Hope Comprehens Canc Ctr, Hematol Hematol Oncol, Duarte, CA USA. [Nademanee, Auayporn] City Hope Comprehens Canc Ctr, Bone Marrow Transplantat, Duarte, CA USA. [Porcu, Pierluigi] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Med Oncol, Columbus, OH 43210 USA. [Porcu, Pierluigi] Solove Res Inst, Med Oncol, Columbus, OH USA. [Press, Oliver] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Med Oncol, Seattle, WA USA. [Press, Oliver] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Hematol Hematol Oncol, Seattle, WA USA. [Rabinovitch, Rachel] Univ Colorado, Ctr Canc, Radiotherapy Radiat Oncol, Boulder, CO 80309 USA. [Reddy, Nishitha] Vanderbilt Ingram Canc Ctr, Hematol Hematol Oncol, Nashville, TN USA. [Reddy, Nishitha] Vanderbilt Ingram Canc Ctr, Bone Marrow Transplantat, Nashville, TN USA. [Reid, Erin] UC San Diego Moores Canc Ctr, Hematol Hematol Oncol, San Diego, CA USA. [Reid, Erin] UC San Diego Moores Canc Ctr, Bone Marrow Transplantat, San Diego, CA USA. [Roberts, Kenneth] Smilow Canc Hosp, Yale Canc Ctr, Radiotherapy Radiat Oncol, New York, NY USA. [Saad, Ayman A.] Univ Alabama Birmingham, Ctr Comprehens Canc, Hematol Hematol Oncol, Birmingham, AL USA. [Saad, Ayman A.] Univ Alabama Birmingham, Ctr Comprehens Canc, Bone Marrow Transplantat, Birmingham, AL USA. [Sokol, Lubomir] H Lee Moffitt Canc Ctr & Res Inst, Med Oncol, Tampa, FL USA. [Sokol, Lubomir] H Lee Moffitt Canc Ctr & Res Inst, Hematol Hematol Oncol, Tampa, FL USA. [Sokol, Lubomir] H Lee Moffitt Canc Ctr & Res Inst, Internal Med, Tampa, FL USA. [Sokol, Lubomir] H Lee Moffitt Canc Ctr & Res Inst, Radiotherapy Radiat Oncol, Tampa, FL USA. [Sokol, Lubomir] H Lee Moffitt Canc Ctr & Res Inst, Bone Marrow Transplantat, Tampa, FL USA. [Swinnen, Lode J.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Hematol Hematol Oncol, Baltimore, MD USA. [Swinnen, Lode J.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Bone Marrow Transplantat, Baltimore, MD USA. [Vose, Julie M.] Fred & Pamela Buffett Canc Ctr, Hematol Hematol Oncol, Bethesda, MD USA. [Vose, Julie M.] Fred & Pamela Buffett Canc Ctr, Bone Marrow Transplantat, Bethesda, MD USA. [Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, Radiotherapy Radiat Oncol, New York, NY USA. [Zafar, Nadeem] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Pathol, Knoxville, TN 37996 USA. [Dwyer, Mary; Sundar, Hema] NCCN, London, England. RP Zelenetz, AD (reprint author), Mem Sloan Kettering Canc Ctr, Med Oncol, New York, NY 10065 USA.; Zelenetz, AD (reprint author), Mem Sloan Kettering Canc Ctr, Internal Med, New York, NY 10025 USA. OI Saad, Ayman /0000-0003-0003-0130 FU NCI NIH HHS [P30 CA016672] NR 172 TC 6 Z9 6 U1 0 U2 3 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 FEB PY 2016 VL 14 IS 2 BP 196 EP 231 PG 36 WC Oncology SC Oncology GA DD0UA UT WOS:000369634300011 PM 26850490 ER PT J AU Sheth, RA Koottappillil, B Kambadakone, A Ganguli, S Thabet, A Mueller, PR AF Sheth, Rahul A. Koottappillil, Brian Kambadakone, Avinash Ganguli, Suvranu Thabet, Ashraf Mueller, Peter R. TI A Quality Improvement Initiative to Reduce Catheter Exchange Rates for Fluoroscopically Guided Gastrostomy Tubes SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; RADIOLOGIC GASTROSTOMY; SINGLE-CENTER; PEG TUBES; EXPERIENCE; PLACEMENT; GASTROJEJUNOSTOMY; COMPLICATIONS; GASTROPEXY; OUTCOMES AB Purpose: To evaluate the effectiveness of a data-driven quality improvement initiative to reduce catheter exchange rates. Materials and Methods: A single-institution retrospective analysis of all percutaneous radiologic gastrostomy (PRG) placement and replacement procedures between January 2010 and July 2015 was conducted. A statistical model predicting the risk for catheter exchange for any reason and exchanges specifically for tube malfunction was created; a quality improvement plan to reduce catheter exchanges was designed and implemented in June 2014. The outcomes for subsequent PRG procedures from July 2014 through March 2015 were followed until July 2015. Results: Between 2010 and June 2014, 1,144 primary PRG procedures and 442 replacement procedures were performed in 1,112 patients. Of the 442 exchange procedures, 289 were "rescue" procedures secondary to catheter malfunction. A quality improvement plan was implemented in June 2014 that encouraged primary gastrojejunostomy catheter and balloon-retained PRG catheter placement and placement of skin sutures in patients considered high risk for catheter dislodgment. From July 2014 through March 2015, 229 PRG catheters were placed, and 71 exchange procedures were performed through July 2015. There was a statistically significant decrease in the number of rescue exchanges performed secondary to catheter malfunction (P = .036). Conclusions: Procedural and patient-specific risk factors for PRG complications were identified, and a statistical model to predict rates of minor complications was created. These findings were used to implement a quality improvement program that resulted in a decrease in PRG exchanges secondary to catheter malfunction. C1 [Sheth, Rahul A.; Koottappillil, Brian; Kambadakone, Avinash; Ganguli, Suvranu; Thabet, Ashraf; Mueller, Peter R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Radiol,Dept Radiol, Gray 290,55 Fruit St, Boston, MA 02114 USA. RP Sheth, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Radiol,Dept Radiol, Gray 290,55 Fruit St, Boston, MA 02114 USA. NR 25 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2016 VL 27 IS 2 BP 251 EP 259 DI 10.1016/j.jvir.2015.10.015 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA DD2UF UT WOS:000369777000017 PM 26656959 ER PT J AU Lopez, E Arellano, R AF Lopez, Emilio Arellano, Ronald TI Neuroendocrine Malignancy Diagnosed via CT-Guided Percutaneous Biopsy of an Isolated Abnormal Cardiophrenic Lymph Node: Case Report SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter C1 [Lopez, Emilio; Arellano, Ronald] Massachusetts Gen Hosp, Div Intervent Radiol, 55 Fruit St, Boston, MA 02114 USA. RP Lopez, E (reprint author), Massachusetts Gen Hosp, Div Intervent Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 5 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2016 VL 27 IS 2 BP 289 EP 290 DI 10.1016/j.jvir.2015.09.015 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA DD2UF UT WOS:000369777000025 PM 26830945 ER PT J AU Menon, MC Ross, MJ AF Menon, Madhav C. Ross, Michael J. TI Epithelial-to-mesenchymal transition of tubular epithelial cells in renal fibrosis: a new twist on an old tale SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID TISSUE GROWTH-FACTOR; KIDNEY FIBROSIS; DISEASE AB Recent publications have questioned whether epithelial-to-mesenchymal transition of tubular epithelial cells is an important contributor to renal fibrosis. Two recent publications describe an intratubular epithelial-to-mesenchymal transition-like program of epithelial cell dedifferentiation that may contribute to the recruitment or proliferation of interstitial myofibroblasts after kidney injury. C1 [Menon, Madhav C.] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA. [Ross, Michael J.] James J Peters VA Med Ctr, Bronx, NY USA. RP Ross, MJ (reprint author), Icahn Sch Med Mt Sinai, Div Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM michael.ross@mssm.edu NR 11 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2016 VL 89 IS 2 BP 263 EP 266 DI 10.1016/j.kint.2015.12.025 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA DD2TO UT WOS:000369775300004 PM 26806826 ER PT J AU Nowak, N Skupien, J Niewczas, MA Yamanouchi, M Major, M Croall, S Smiles, A Warram, JH Bonventre, JV Krolewski, AS AF Nowak, Natalia Skupien, Jan Niewczas, Monika A. Yamanouchi, Masayuki Major, Melissa Croall, Stephanie Smiles, Adam Warram, James H. Bonventre, Joseph V. Krolewski, Andrzej S. TI Increased plasma kidney injury molecule-1 suggests early progressive renal decline in non-proteinuric patients with type 1 diabetes SO KIDNEY INTERNATIONAL LA English DT Article DE early progressive renal decline; markers of glomerular and tubular damage; type 1 diabetes ID GLOMERULAR-FILTRATION-RATE; ACID-BINDING PROTEIN; SERUM URIC-ACID; NONPROTEINURIC PATIENTS; PREDICTS PROGRESSION; URINARY BIOMARKERS; TUBULAR MARKERS; CYSTATIN-C; FOLLOW-UP; NEPHROPATHY AB Progressively decreasing glomerular filtration rate (GFR), or renal decline, is seen in patients with type 1 diabetes (T1D) and normoalbuminuria or microalbuminuria. Here we examined the associations of kidney injury molecule-1 (KIM-1) in plasma and urine with the risk of renal decline and determine whether those associations are independent of markers of glomerular damage. The study group comprised patients with T1D from the 2nd Joslin Kidney Study of which 259 had normoalbuminuria and 203 had microalbuminuria. Serial measurements over 4 to 10 years of follow-up (median 8 years) of serum creatinine and cystatin C were used jointly to estimate eGFRcr-cys slopes and time of onset of CKD stage 3 or higher. Baseline urinary excretion of IgG(2) and albumin were used as markers of glomerular damage, and urinary excretion of KIM-1 and its plasma concentration were used as markers of proximal tubular damage. All patients had normal renal function at baseline. During follow-up, renal decline (eGFRcr-cys loss 3.3% or more per year) developed in 96 patients and 62 progressed to CKD stage 3. For both outcomes, the risk rose with increasing baseline levels of plasma KIM-1. In multivariable models, elevated baseline plasma KIM-1 was strongly associated with risk of early progressive renal decline, regardless of baseline clinical characteristics, serum TNFR1 or markers of glomerular damage. Thus, damage to proximal tubules may play an independent role in the development of early progressive renal decline in non-proteinuric patients with T1D. C1 [Nowak, Natalia; Skupien, Jan; Niewczas, Monika A.; Yamanouchi, Masayuki; Major, Melissa; Croall, Stephanie; Smiles, Adam; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. [Nowak, Natalia; Skupien, Jan; Niewczas, Monika A.; Yamanouchi, Masayuki; Bonventre, Joseph V.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Nowak, Natalia; Skupien, Jan] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. [Bonventre, Joseph V.] Brigham & Women Hosp, Div Renal, Boston, MA USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, One Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU National Institutes of Health [DK-041526, DK-072381]; JDRF grant: Biomarkers of Diabetic Nephropathy Collaborative Research Initiative (DN Bio) [3-SRA-2015-106-Q-R] FX This study was supported by National Institutes of Health grants: DK-041526 to ASK, and DK-072381 to JVB. This study was supported by JDRF grant: Biomarkers of Diabetic Nephropathy Collaborative Research Initiative (DN Bio) No. 3-SRA-2015-106-Q-R to ASK. NR 34 TC 8 Z9 8 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2016 VL 89 IS 2 BP 459 EP 467 DI 10.1038/ki.2015.314 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA DD2TO UT WOS:000369775300025 PM 26509588 ER PT J AU Shaw, AT Gandhi, L Gadgeel, S Riely, GJ Cetnar, J West, H Camidge, DR Socinski, MA Chiappori, A Mekhail, T Chao, BH Borghaei, H Gold, KA Zeaiter, A Bordogna, W Balas, B Puig, O Henschel, V Ou, SHI AF Shaw, Alice T. Gandhi, Leena Gadgeel, Shirish Riely, Gregory J. Cetnar, Jeremy West, Howard Camidge, D. Ross Socinski, Mark A. Chiappori, Alberto Mekhail, Tarek Chao, Bo H. Borghaei, Hossein Gold, Kathryn A. Zeaiter, Ali Bordogna, Walter Balas, Bogdana Puig, Oscar Henschel, Volkmar Ou, Sai-Hong Ignatius CA Study Investigators TI Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID ANAPLASTIC LYMPHOMA KINASE; BRAIN METASTASES; INHIBITOR; MODELS; CHEMOTHERAPY; CERITINIB; CH5424802; CRITERIA; SAFETY AB Background Alectinib-a highly selective, CNS-active, ALK inhibitor-showed promising clinical activity in crizotinibnaive and crizotinib-resistant patients with ALK-rearranged (ALK-positive) non-small-cell lung cancer (NSCLC). We aimed to assess the safety and effi cacy of alectinib in patients with ALK-positive NSCLC who progressed on previous crizotinib. Methods We did a phase 2 study at 27 centres in the USA and Canada. We enrolled patients aged 18 years or older with stage IIIB-IV, ALK-positive NSCLC who had progressed after crizotinib. Patients were treated with oral alectinib 600 mg twice daily until progression, death, or withdrawal. The primary endpoint was the proportion of patients achieving an objective response by an independent review committee using Response Evaluation Criteria in Solid Tumors, version 1.1. Response endpoints were assessed in the response-evaluable population (ie, patients with measurable disease at baseline who received at least one dose of study drug), and effi cacy and safety analyses were done in the intention-to-treat population (all enrolled patients). This study is registered with ClinicalTrials. gov, number NCT01871805. The study is ongoing and patients are still receiving treatment. Findings Between Sept 4, 2013, and Aug 4, 2014, 87 patients were enrolled into the study (intention-to-treat population). At the time of the primary analysis (median follow-up 4 . 8 months [IQR 3 . 3-7 . 1]), 33 of 69 patients with measurable disease at baseline had a confi rmed partial response; thus, the proportion of patients achieving an objective response by the independent review committee was 48% (95% CI 36-60). Adverse events were predominantly grade 1 or 2, most commonly constipation (31 [36%]), fatigue (29 [33%]), myalgia 21 [24%]), and peripheral oedema 20 [23%]). The most common grade 3 and 4 adverse events were changes in laboratory values, including increased blood creatine phosphokinase (seven [8%]), increased alanine aminotransferase (fi ve [6%]), and increased aspartate aminotransferase (four [5%]). Two patients died: one had a haemorrhage (judged related to study treatment), and one had disease progression and a history of stroke (judged unrelated to treatment). C1 [Shaw, Alice T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gadgeel, Shirish] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Cetnar, Jeremy] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [West, Howard] Swedish Canc Ctr, Seattle, WA USA. [Camidge, D. Ross] Univ Colorado, Boulder, CO 80309 USA. [Socinski, Mark A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Chiappori, Alberto] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Mekhail, Tarek] Florida Hosp Canc Inst, Orlando, FL USA. [Chao, Bo H.] Ohio State Univ, Columbus, OH 43210 USA. [Borghaei, Hossein] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Gold, Kathryn A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zeaiter, Ali; Bordogna, Walter; Balas, Bogdana; Puig, Oscar; Henschel, Volkmar] F Hoffmann La Roche, Basel, Switzerland. [Ou, Sai-Hong Ignatius] Univ Calif Irvine, Sch Med, Family Comprehens Canc Ctr, Orange, CA 92668 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ASHAW1@mgh.harvard.edu OI Gandhi, Leena/0000-0002-2398-9179 FU F Hoffmann-La Roche; US National Institutes of Health grant [5R01CA164273] FX This study was funded by F Hoffmann-La Roche. ATS is supported by a US National Institutes of Health grant (5R01CA164273). Third-party editorial assistance and graphic support, under the direction of the authors, was provided by Joanna Musgrove of Gardiner-Caldwell Communications, funded by F Hoffmann-La Roche. NR 28 TC 86 Z9 91 U1 8 U2 12 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 FEB PY 2016 VL 17 IS 2 BP 234 EP 242 DI 10.1016/S1470-2045(15)00488-X PG 9 WC Oncology SC Oncology GA DD0MK UT WOS:000369613900052 PM 26708155 ER PT J AU Vale, CL Burdett, S Rydzewska, LHM Albiges, L Clarke, NW Fisher, D Fizazi, K Gravis, G James, ND Mason, MD Parmar, MKB Sweeney, CJ Sydes, MR Tombal, B Tierney, JF AF Vale, Claire L. Burdett, Sarah Rydzewska, Larysa H. M. Albiges, Laurence Clarke, Noel W. Fisher, David Fizazi, Karim Gravis, Gwenaelle James, Nicholas D. Mason, Malcolm D. Parmar, Mahesh K. B. Sweeney, Christopher J. Sydes, Matthew R. Tombal, Bertrand Tierney, Jayne F. CA STOpCaP Steering Grp TI Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data SO LANCET ONCOLOGY LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED-TRIAL; PHASE-III TRIAL; GETUG-AFU 15; ZOLEDRONIC ACID; OPEN-LABEL; RADICAL PROSTATECTOMY; CLINICAL-TRIALS; PLUS DOCETAXEL AB Background Results from large randomised controlled trials combining docetaxel or bisphosphonates with standard of care in hormone-sensitive prostate cancer have emerged. In order to investigate the effects of these therapies and to respond to emerging evidence, we aimed to systematically review all relevant trials using a framework for adaptive meta-analysis. Methods For this systematic review and meta-analysis, we searched MEDLINE, Embase, LILACS, and the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant randomised controlled trials (published, unpublished, and ongoing) comparing either standard of care with or without docetaxel or standard of care with or without bisphosphonates for men with high-risk localised or metastatic hormone-sensitive prostate cancer. For each trial, we extracted hazard ratios (HRs) of the effects of docetaxel or bisphosphonates on survival (time from randomisation until death from any cause) and failure-free survival (time from randomisation to biochemical or clinical failure or death from any cause) from published trial reports or presentations or obtained them directly from trial investigators. HRs were combined using the fixed-effect model (Mantel-Haenzsel). Findings We identified five eligible randomised controlled trials of docetaxel in men with metastatic (M1) disease. Results from three (CHAARTED, GETUG-15, STAMPEDE) of these trials (2992 [93%] of 3206 men randomised) showed that the addition of docetaxel to standard of care improved survival. The HR of 0 . 77 (95% CI 0 . 68-0 . 87; p<0 . 0001) translates to an absolute improvement in 4-year survival of 9% (95% CI 5-14). Docetaxel in addition to standard of care also improved failure-free survival, with the HR of 0 . 64 (0 . 58-0 . 70; p<0 . 0001) translating into a reduction in absolute 4-year failure rates of 16% (95% CI 12-19). We identified 11 trials of docetaxel for men with locally advanced disease (M0). Survival results from three (GETUG-12, RTOG 0521, STAMPEDE) of these trials (2121 [53%] of 3978 men) showed no evidence of a benefit from the addition of docetaxel (HR 0 . 87 [95% CI 0 . 69-1 . 09]; p=0 . 218), whereas failure-free survival data from four (GETUG-12, RTOG 0521, STAMPEDE, TAX 3501) of these trials (2348 [59%] of 3978 men) showed that docetaxel improved failure-free survival (0 . 70 [0 . 61-0 . 81]; p<0 . 0001), which translates into a reduced absolute 4-year failure rate of 8% (5-10). We identified seven eligible randomised controlled trials of bisphosphonates for men with M1 disease. Survival results from three of these trials (2740 [88%] of 3109 men) showed that addition of bisphosphonates improved survival (0 . 88 [0 . 79-0 . 98]; p=0 . 025), which translates to 5% (1-8) absolute improvement, but this result was influenced by the positive result of one trial of sodium clodronate, and we found no evidence of a benefit from the addition of zoledronic acid (0 . 94 [0 . 83-1 . 07]; p=0 . 323), which translates to an absolute improvement in survival of 2% (-3 to 7). Of 17 trials of bisphosphonates for men with M0 disease, survival results from four trials (4079 [66%] of 6220 men) showed no evidence of benefit from the addition of bisphosphonates (1 . 03 [0 . 89-1 . 18]; p=0 . 724) or zoledronic acid (0 . 98 [0 . 82-1 . 16]; p=0 . 782). Failure-free survival definitions were too inconsistent for formal meta-analyses for the bisphosphonate trials. C1 [Vale, Claire L.; Burdett, Sarah; Rydzewska, Larysa H. M.; Fisher, David; Parmar, Mahesh K. B.; Sydes, Matthew R.; Tierney, Jayne F.] UCL, MRC Clin Trials Unit, London WC2B 6NH, England. [Albiges, Laurence; Fizazi, Karim] Inst Gustave Roussy, Paris, France. [Clarke, Noel W.] Christie & Salford Royal NHS Fdn Trusts, Dept Urol, Manchester, Lancs, England. [Gravis, Gwenaelle] Inst J Paoli I Calmettes, Dept Med Oncol, F-13009 Marseille, France. [James, Nicholas D.] Univ Warwick, Warwick Canc Res Unit, Coventry CV4 7AL, W Midlands, England. [James, Nicholas D.] Univ Birmingham, Sch Med, Univ Hosp Birmingham NHS Fdn Trust, Birmingham, W Midlands, England. [Mason, Malcolm D.] Cardiff Univ, Sch Med, Velindre Hosp, Cardiff CF10 3AX, S Glam, Wales. [Sweeney, Christopher J.] Dana Farber Canc Inst, Lank Ctr Genitourinary Canc, Boston, MA 02115 USA. [Tombal, Bertrand] Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium. RP Vale, CL (reprint author), UCL, MRC Clin Trials Unit, Meta Anal Grp, London WC2B 6NH, England. EM claire.vale@ucl.ac.uk OI Sydes, Matthew/0000-0002-9323-1371 FU UK Medical Research Council FX The STOpCaP Steering Group thanks all patients who participated in the trials and contributed to this research. The meta-analysis would not have been possible without their participation or without the institutions that carried out the trials. We thank the principal investigators of the GETUG-15, CHAARTED, and STAMPEDE trials for supplying additional information that we have used in these analyses. The Project Management Group was funded by the UK Medical Research Council. NR 52 TC 32 Z9 32 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 FEB PY 2016 VL 17 IS 2 BP 243 EP 256 DI 10.1016/S1470-2045(15)00489-1 PG 14 WC Oncology SC Oncology GA DD0MK UT WOS:000369613900053 PM 26718929 ER PT J AU Woods, NF Hohensee, C Carpenter, JS Cohen, L Ensrud, K Freeman, EW Guthrie, KA Joffe, H LaCroix, AZ Otte, JL AF Woods, Nancy Fugate Hohensee, Chancellor Carpenter, Janet S. Cohen, Lee Ensrud, Kristine Freeman, Ellen W. Guthrie, Katherine A. Joffe, Hadine LaCroix, Andrea Z. Otte, Julie L. TI Symptom clusters among MsFLASH clinical trial participants SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Hot flashes; Menopause; Mood; Pain; Sleep disturbances; Symptom clusters ID RANDOMIZED CONTROLLED-TRIAL; EARLY POSTMENOPAUSE OBSERVATIONS; HEALTHY MENOPAUSAL WOMEN; SLEEP QUALITY INDEX; MIDDLE-AGED WOMEN; HOT FLASHES; VASOMOTOR SYMPTOMS; MUSCULOSKELETAL PAIN; OF-LIFE; TRANSITION AB Objective:Our objective was to identify symptom clusters using standardized measures completed by participants in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health clinical trial at baseline, including hot flash interference, and sleep, depressive, anxiety, and pain symptoms.Methods:Data from all women randomized to interventions and controls from Menopausal Strategies: Finding Lasting Answers to Symptoms and Health studies 1, 2, and 3 (N=899) were included; 797 with complete data were used in the analyses. Scores from standardized measures obtained at baseline included the following: Hot Flash-Related Daily Interference Scale, Insomnia Severity Index, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9 measure of depressed mood, Generalized Anxiety Disorder, and Brief Pain Inventory PEG scores (pain intensity [P], interference with enjoyment of life [E], and interference with daily activity [G]). Latent class analysis was used to identify symptom clusters using standardized scale scores and their established cut points.Results:We identified five classes using the Bayesian Information Criterion and the Akaike Information Criterion. Women in classes 1 and 2 had high hot flash interference levels relative to the others, and class 1 (10.5% of total) included severe hot flash interference, severe sleep symptoms, and moderately severe pain symptoms (hot flash, sleep, pain). In class 2 (14.1%), severe hot flash interference was paired with the severe sleep symptoms, and moderate to severe depressed and anxious mood symptoms and pain (hot flash, sleep, mood, pain). In class 3 (39.6%), women reported moderately severe sleep symptoms with moderate hot flash interference, and low severity mood and pain symptoms (hot flash, sleep). Those in class 4 (7.0%) reported moderate hot flash interference with severe levels of anxiety and depressed mood symptoms, but low levels of other symptoms (hot flash, mood). Women in class 5 (28.7%) reported the lowest levels of all the five symptoms (low severity symptoms).Conclusions:Women meeting hot flash frequency criteria for inclusion in clinical trials exhibited multiple co-occurring symptoms that clustered into identifiable groups according to symptom interference and severity. Variability of symptom profiles between the classes was evident, indicating that the classes were composed of differing symptom types and not simply differing severity levels. These symptom clusters may be useful phenotypes for differentiating treatment effects or evaluating associations with biomarkers or genes. C1 [Woods, Nancy Fugate] Univ Washington, Biobehav Nursing, Seattle, WA 98195 USA. [Hohensee, Chancellor; Guthrie, Katherine A.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Carpenter, Janet S.; Otte, Julie L.] Indiana Univ, Sch Nursing, Sci Nursing Care, Indianapolis, IN 46204 USA. [Cohen, Lee] Ctr Womens Mental Hlth, Boston, MA USA. [Cohen, Lee] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. [Ensrud, Kristine] Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA. [Ensrud, Kristine] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Freeman, Ellen W.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Freeman, Ellen W.] Univ Penn, Perelman Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Freeman, Ellen W.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Joffe, Hadine] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Joffe, Hadine] Dana Farber Canc Inst, Boston, MA 02115 USA. [LaCroix, Andrea Z.] Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92103 USA. RP Woods, NF (reprint author), Univ Washington, Biobehav Nursing, Seattle, WA 98195 USA.; Woods, NF (reprint author), Univ Washington, Seattle, WA 98195 USA. EM nfwoods@u.washington.edu FU NCRR NIH HHS [UL1RR02571]; NIA NIH HHS [U01AG032700, U01 AG032656, U01 AG032659, U01 AG032669, U01 AG032682, U01 AG032699, U01 AG032700, U01AG032659, U01AG032669, U01AG032682, U01AG032699] NR 40 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD FEB PY 2016 VL 23 IS 2 BP 158 EP 165 DI 10.1097/GME.0000000000000516 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DD5TX UT WOS:000369988500009 PM 26506500 ER PT J AU Meyer, F Freeman, MP Petrillo, L Barsky, M Galvan, T Kim, S Cohen, L Joffe, H AF Meyer, Fremonta Freeman, Marlene P. Petrillo, Laura Barsky, Maria Galvan, Thania Kim, Semmie Cohen, Lee Joffe, Hadine TI Armodafinil for fatigue associated with menopause: an open-label trial SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Fatigue; Menopause; Armodafinil; Modafinil; Hot flashes; Quality of life ID CLIMACTERIC SYMPTOMS; WOMEN; EFFICACY; DEPRESSION; SLEEPINESS; SEVERITY; QUESTIONNAIRE; CHEMOTHERAPY; NARCOLEPSY; MODAFINIL AB Objective:This study aims to obtain preliminary data on the efficacy of armodafinil for improving menopause-related fatigue and quality of life.Methods:Women (aged 40-65 y) experiencing menopause-related fatigue received open-label armodafinil therapy (up to 150mg/d) for 4 weeks. Changes from baseline in Brief Fatigue Inventory score and Menopause-Specific Quality of Life (MENQOL) physical domain score were examined using the Wilcoxon signed rank test. Exploratory analyses examined the effects of armodafinil on hot flashes, overall quality of life, insomnia, depression, anxiety, and perceived cognitive performance. After open-label treatment, participants were randomized to double-blind continuation of armodafinil versus placebo for 2 weeks to examine whether treatment discontinuation would precipitate symptom recurrence.Results:Of 29 eligible participants, 20 women (69.0%) completed the trial. During treatment with armodafinil (mean dose, 120mg/d), median Brief Fatigue Inventory scores decreased by 57.7% from 5.2 (interquartile range [IQR], 4.6-6.2) to 2.2 (IQR, 1.1-4.4; P=0.0002), and median MENQOL physical domain scores decreased by 51.3% from 3.9 (IQR, 2.3-4.8) to 1.9 (IQR, 1.3-2.7; P=0.0001). Median hot flashes for 24hours decreased by 48.3% from 2.9 (IQR, 1.1-4.6) to 1.5 (IQR, 0.4-2.4; P=0.0005). Improvements in MENQOL total score (49%; P=0.0001), cognitive function (59.2%; P=0.0002), depressive symptoms (64.7%; P=0.0006), insomnia (72.7%; P=0.0012), and excessive sleepiness (57.1%; P=0.0006) were noted. Randomized continuation (n=10) or discontinuation (n=10) did not indicate group differences. Armodafinil was well-tolerated; three women (12%) were withdrawn for adverse events.Conclusions:These preliminary results suggest a therapeutic effect of armodafinil on fatigue affecting quality of life during menopause, and a potential benefit for other menopause-related symptoms. C1 [Meyer, Fremonta; Galvan, Thania; Kim, Semmie; Joffe, Hadine] Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. [Meyer, Fremonta; Joffe, Hadine] Dana Farber Canc Inst, Dept Psychooncol & Palliat Care, Boston, MA 02115 USA. [Freeman, Marlene P.; Petrillo, Laura; Barsky, Maria; Cohen, Lee; Joffe, Hadine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Joffe, H (reprint author), Brigham & Womens Hosp, BB232C,75 Francis St, Boston, MA 02115 USA. EM hjoffe@partners.org NR 30 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 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD FEB PY 2016 VL 23 IS 2 BP 209 EP 214 DI 10.1097/GME.0000000000000505 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DD5TX UT WOS:000369988500015 PM 26125538 ER PT J AU Burns, TM Smith, GA Allen, JA Amato, AA Arnold, WD Barohn, R Benatar, M Bird, SJ Bromberg, M Chahin, N Ciafaloni, E Cohen, JA Corse, A Crum, BA David, WS Dimberg, E De Sousa, EA Donofrio, PD Dyck, PJB Engel, AG Ensrud, ER Ferrante, M Freimer, M Gable, KL Gibson, S Gilchrist, JM Goldstein, JM Gooch, CL Goodman, BP Gorelov, D Gospe, SM Goyal, NA Guidon, AC Guptill, JT Gutmann, L Gutmann, L Gwathmey, K Harati, Y Harper, CM Hehir, MK Hobson-Webb, LD Howard, JF Jackson, CE Johnson, N Jones, SM Juel, VC Kaminski, HJ Karam, C Kennelly, KD Khella, S Khoury, J Kincaid, JC Kissel, JT Kolb, N Lacomis, D Ladha, S Larriviere, D Lewis, RA Li, YB Litchy, WJ Logigian, E Lou, JS MacGowen, DJL Maselli, R Massey, JM Mauermann, ML Mathews, KD Meriggioli, MN Miller, RG Moon, JS Mozaffar, T Nations, SP Nowak, RJ Ostrow, LW Pascuzzi, RM Peltier, A Ruzhansky, K Richman, DP Ross, MA Rubin, DI Russell, JA Sachs, GM Salajegheh, MK Saperstein, DS Scelsa, S Selcen, D Shaibani, A Shieh, PB Silvestri, NJ Singleton, JR Smith, BE So, YT Solorzano, G Sorenson, EJ Srinivasen, J Tavee, J Tawil, R Thaisetthawatkul, P Thornton, C Trivedi, J Vernino, S Wang, AK Webb, TA Weiss, MD Windebank, AJ Wolfe, GI AF Burns, Ted M. Smith, Gordon A. Allen, Jeffrey A. Amato, Anthony A. Arnold, W. David Barohn, Richard Benatar, Michael Bird, Shawn J. Bromberg, Mark Chahin, Nizar Ciafaloni, Emma Cohen, Jeffrey A. Corse, Andrea Crum, Brian A. David, William S. Dimberg, Elliot De Sousa, Eduardo A. Donofrio, Peter D. Dyck, P. James B. Engel, Andrew G. Ensrud, Erik R. Ferrante, Mark Freimer, Miriam Gable, Karissa L. Gibson, Summer Gilchrist, James M. Goldstein, Jonathan M. Gooch, Clifton L. Goodman, Brent P. Gorelov, Dmitri Gospe, Sidney M., Jr. Goyal, Namita A. Guidon, Amanda C. Guptill, Jeffrey T. Gutmann, Laurie Gutmann, Ludwig Gwathmey, Kelly Harati, Yadollah Harper, C. Michel, Jr. Hehir, Michael K. Hobson-Webb, Lisa D. Howard, James F., Jr. Jackson, Carlayne E. Johnson, Nicholas Jones, Sarah M. Juel, Vern C. Kaminski, Henry J. Karam, Chafic Kennelly, Kathleen D. Khella, Sami Khoury, Julie Kincaid, John C. Kissel, John T. Kolb, Noah Lacomis, David Ladha, Shafeeq Larriviere, Daniel Lewis, Richard A. Li, Yuebing Litchy, William J. Logigian, Eric Lou, Jau-Shin MacGowen, Daniel J. L. Maselli, Ricardo Massey, Janice M. Mauermann, Michelle L. Mathews, Katherine D. Meriggioli, Matthew N. Miller, Robert G. Moon, Joon-Shik Mozaffar, Tahseen Nations, Sharon P. Nowak, Richard J. Ostrow, Lyle W. Pascuzzi, Robert M. Peltier, Amanda Ruzhansky, Katherine Richman, David P. Ross, Mark A. Rubin, Devon I. Russell, James A. Sachs, George M. Salajegheh, Mohammad Kian Saperstein, David S. Scelsa, Stephen Selcen, Duygu Shaibani, Aziz Shieh, Perry B. Silvestri, Nicholas J. Singleton, J. Rob Smith, Benn E. So, Yuen T. Solorzano, Guillermo Sorenson, Eric J. Srinivasen, Jayashri Tavee, Jinny Tawil, Rabi Thaisetthawatkul, Pariwat Thornton, Charles Trivedi, Jaya Vernino, Steven Wang, Annabel K. Webb, Tyler A. Weiss, Michael D. Windebank, Anthony J. Wolfe, Gil I. TI EDITORIAL BY CONCERNED PHYSICIANS: UNINTENDED EFFECT OF THE ORPHAN DRUG ACT ON THE POTENTIAL COST OF 3,4-DIAMINOPYRIDINE SO MUSCLE & NERVE LA English DT Editorial Material ID EATON MYASTHENIC SYNDROME; DOUBLE-BLIND; PLACEBO C1 [Burns, Ted M.; Gwathmey, Kelly; Jones, Sarah M.; Solorzano, Guillermo] Univ Virginia, Dept Neurol, Charlottesville, VA 22908 USA. [Smith, Gordon A.; Bromberg, Mark; Gibson, Summer; Johnson, Nicholas; Kolb, Noah; Singleton, J. Rob] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Allen, Jeffrey A.] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. [Amato, Anthony A.; Salajegheh, Mohammad Kian] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Arnold, W. David] Ohio State Univ, Dept Neurol & Phys Med & Rehabil, Columbus, OH 43210 USA. [Barohn, Richard] Univ Kansas, Dept Neurol, Kansas City, KS USA. [Benatar, Michael] Univ Miami, Dept Neurol, Miami, FL USA. [Bird, Shawn J.; Khella, Sami] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Chahin, Nizar] Univ Connecticut, Dept Neurol, Farmington, CT USA. [Ciafaloni, Emma; Logigian, Eric; Tawil, Rabi; Thornton, Charles] Univ Rochester, Dept Neurol, Rochester, NY USA. [Cohen, Jeffrey A.] Geisel Sch Med Dartmouth, Dept Neurol, Lebanon, NH USA. [Corse, Andrea; Ostrow, Lyle W.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Crum, Brian A.; Dyck, P. James B.; Engel, Andrew G.; Harper, C. Michel, Jr.; Litchy, William J.; Mauermann, Michelle L.; Selcen, Duygu; Sorenson, Eric J.; Windebank, Anthony J.] Mayo Clin, Dept Neurol, Rochester, MN USA. [David, William S.; Guidon, Amanda C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Dimberg, Elliot; Kennelly, Kathleen D.; Rubin, Devon I.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [De Sousa, Eduardo A.; Moon, Joon-Shik; Webb, Tyler A.] Univ Oklahoma, Dept Neurol, Oklahoma City, OK USA. [Donofrio, Peter D.; Peltier, Amanda] Vanderbilt Univ, Dept Neurol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Ensrud, Erik R.] Boston Vet Affairs, Dept Neurol, Boston, MA USA. [Ferrante, Mark] Univ Tennessee, Hlth Sci Ctr, Dept Neurol, Memphis, TN USA. [Freimer, Miriam; Kissel, John T.] Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA. [Gable, Karissa L.; Guptill, Jeffrey T.; Hobson-Webb, Lisa D.; Juel, Vern C.; Massey, Janice M.] Duke Univ, Dept Neurol, Durham, NC USA. [Gilchrist, James M.] So Illinois Univ, Sch Med, Dept Neurol, Springfield, IL USA. [Goldstein, Jonathan M.] Hosp Special Surg, Dept Neurol, 535 E 70th St, New York, NY 10021 USA. [Gooch, Clifton L.] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA. [Goodman, Brent P.; Ross, Mark A.; Smith, Benn E.] Mayo Clin, Dept Neurol, Scottsdale, AZ USA. [Gorelov, Dmitri] Crystal Run Healthcare, Middletown, NY USA. [Gospe, Sidney M., Jr.; Weiss, Michael D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Goyal, Namita A.; Mozaffar, Tahseen] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Gutmann, Laurie; Gutmann, Ludwig; Mathews, Katherine D.] Univ Iowa, Div Neurol, Iowa City, IA USA. [Harati, Yadollah] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Hehir, Michael K.] Univ Vermont, Dept Neurol, Burlington, VT USA. [Howard, James F., Jr.; Karam, Chafic] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Jackson, Carlayne E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol & Otolaryngol, San Antonio, TX 78229 USA. [Kaminski, Henry J.] George Washington Univ, Dept Neurol, Washington, DC USA. [Khoury, Julie] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. [Kincaid, John C.; Pascuzzi, Robert M.] Indiana Univ, Dept Neurol, Indianapolis, IN 46204 USA. [Lacomis, David] Univ Pittsburgh, Dept Neurol & Pathol, Pittsburgh, PA USA. [Ladha, Shafeeq] Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA. [Larriviere, Daniel] Ochsner Neurosci Inst, Dept Neurol, New Orleans, LA USA. [Lewis, Richard A.] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA. [Li, Yuebing; Tavee, Jinny] Cleveland Clin, Dept Neurol, Cleveland, OH 44106 USA. [Lou, Jau-Shin] Univ N Dakota, Sanford Hlth, Dept Neurol, Fargo, ND USA. [MacGowen, Daniel J. L.; Scelsa, Stephen] Mt Sinai Beth Israel Hosp, Dept Neurol, New York, NY USA. [Maselli, Ricardo; Richman, David P.] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [Meriggioli, Matthew N.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Miller, Robert G.] Calif Pacific Med Ctr, Dept Neurosci, San Francisco, CA USA. [Nations, Sharon P.; Vernino, Steven] Univ Texas Southwestern, Dept Neurol & Neurotherapeut, Dallas, TX USA. [Nowak, Richard J.; Trivedi, Jaya] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Ruzhansky, Katherine] Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. [Russell, James A.; Srinivasen, Jayashri] Lahey Hosp & Med Ctr, Dept Neurol, Burlington, MA USA. [Sachs, George M.] Brown Univ, Alpert Med Sch, Dept Neurol, Providence, RI 02912 USA. [Saperstein, David S.] Phoenix Neurol Associates, Phoenix, AZ USA. [Shaibani, Aziz] Nerve & Muscle Ctr Texas, Houston, TX USA. [Shieh, Perry B.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Silvestri, Nicholas J.; Wolfe, Gil I.] SUNY Buffalo, Dept Neurol, Buffalo, NY 14260 USA. [So, Yuen T.] Stanford Univ, Dept Neurol, Palo Alto, CA 94304 USA. [Thaisetthawatkul, Pariwat] Univ Nebraska, Dept Neurol, Omaha, NE 68182 USA. [Wang, Annabel K.] Vet Affairs Long Beach Healthcare Syst, Dept Neurol, Long Beach, CA USA. RP Burns, TM (reprint author), Univ Virginia, Dept Neurol, Charlottesville, VA 22908 USA. EM tmb8r@virginia.edu RI Gooch, Clifton/M-1874-2016; OI Gooch, Clifton/0000-0002-2210-2038; Howard, James/0000-0002-7136-8617; Peltier, Amanda/0000-0003-1097-7715 NR 14 TC 2 Z9 2 U1 1 U2 7 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 FEB PY 2016 VL 53 IS 2 BP 165 EP 168 DI 10.1002/mus.25009 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DD3RE UT WOS:000369839500001 PM 26662952 ER PT J AU Benatar, M Boylan, K Jeromin, A Rutkove, SB Berry, J Atassi, N Bruijn, L AF Benatar, Michael Boylan, Kevin Jeromin, Andreas Rutkove, Seward B. Berry, James Atassi, Nazem Bruijn, Lucie TI ALS BIOMARKERS FOR THERAPY DEVELOPMENT: STATE OF THE FIELD AND FUTURE DIRECTIONS SO MUSCLE & NERVE LA English DT Review DE ALS; biomarkers; disease progression; predictive; pharmacodynamic; prognostic ID AMYOTROPHIC-LATERAL-SCLEROSIS; ELECTRICAL-IMPEDANCE MYOGRAPHY; TRANSCRANIAL MAGNETIC STIMULATION; NEUROFILAMENT HEAVY-CHAIN; VOXEL-BASED MORPHOMETRY; UNIT NUMBER ESTIMATION; URIC-ACID LEVELS; POSITRON-EMISSION-TOMOGRAPHY; SUBUNIT PNF-H; DISEASE PROGRESSION AB Biomarkers have become the focus of intense research in the field of amyotrophic lateral sclerosis (ALS), with the hope that they might aid therapy development efforts. Notwithstanding the discovery of many candidate biomarkers, none have yet emerged as validated tools for drug development. In this review we present a nuanced view of biomarkers based on the perspective of the Food and Drug Administration; highlight the distinction between discovery and validation; describe existing and emerging resources; review leading biological fluid-based, electrophysiological, and neuroimaging candidates relevant to therapy development efforts; discuss lessons learned from biomarker initiatives in related neurodegenerative diseases; and outline specific steps that we, as a field, might take to hasten the development and validation of biomarkers that will prove useful in enhancing efforts to develop effective treatments for ALS patients. Most important among these is the proposal to establish a federated ALS Biomarker Consortium in which all interested and willing stakeholders may participate with equal opportunity to contribute to the broader mission of biomarker development and validation. C1 [Benatar, Michael] Univ Miami, Dept Neurol, Miami, FL 33136 USA. [Boylan, Kevin] Mayo Clin Jacksonville, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. [Jeromin, Andreas] Iron Horse Diagnost, Scottsdale, AZ USA. [Rutkove, Seward B.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Berry, James; Atassi, Nazem] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bruijn, Lucie] ALS Assoc, Washington, DC USA. RP Benatar, M (reprint author), Univ Miami, Dept Neurol, Miami, FL 33136 USA. EM mbenatar@miami.edu FU CReATe Consortium, is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the ORDR, NCATS [U54-NS-092091]; NCATS; NINDS; Iron Horse Diagnostics, Inc.; Skulpt Inc.; Biogen; Voyager Therapeutics; GSK; Cytokinetics; Brainstorm Cell Therapeutics; Novartis; ALS Therapy Development Institute; ALS Association; MDA; NIH FX We are grateful to Richard Robinson for his careful review and edits to this manuscript. This work was supported in part by the CReATe Consortium (U54-NS-092091), which is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the ORDR, NCATS. CReATe is funded through collaboration between NCATS and NINDS. Andreas Jeromin is a paid employee and shareholder of Iron Horse Diagnostics, Inc. Seward Rutkove owns equity, receives consulting fees, and owns patent rights in Skulpt Inc. Nazem Atassi receives consulting fees from Biogen. James D. Berry has consulted with Biogen Idec and Neuraltus Pharmaceuticals and has received research support from Voyager Therapeutics, GSK, Cytokinetics, Brainstorm Cell Therapeutics, Novartis, ALS Therapy Development Institute, ALS Association, MDA, and NIH. NR 116 TC 4 Z9 5 U1 4 U2 22 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 FEB PY 2016 VL 53 IS 2 BP 169 EP 182 DI 10.1002/mus.24979 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DD3RE UT WOS:000369839500002 PM 26574709 ER PT J AU Heatwole, C Bode, R Johnson, NE Dekdebrun, J Dilek, N Eichinger, K Hilbert, JE Logigian, E Luebbe, E Martens, W Mcdermott, MP Pandya, S Puwanant, A Rothrock, N Thornton, C Vickrey, BG Victorson, D Moxley, RT AF Heatwole, Chad Bode, Rita Johnson, Nicholas E. Dekdebrun, Jeanne Dilek, Nuran Eichinger, Katy Hilbert, James E. Logigian, Eric Luebbe, Elizabeth Martens, William Mcdermott, Michael P. Pandya, Shree Puwanant, Araya Rothrock, Nan Thornton, Charles Vickrey, Barbara G. Victorson, David Moxley, Richard T., III TI MYOTONIC DYSTROPHY HEALTH INDEX: CORRELATIONS WITH CLINICAL TESTS AND PATIENT FUNCTION SO MUSCLE & NERVE LA English DT Article DE muscle disease; myotonic dystrophy Type-1; patient-relevant; patient-reported outcome measure; quality of life; therapeutic trial ID QUALITY-OF-LIFE; FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY; ACTIVITY RATING-SCALES; ADULT MUSCLE DISEASE; NATURAL-HISTORY; THERAPEUTIC TRIALS; DUCHENNE DYSTROPHY; ACTUALLY MEASURE; CTG REPEAT; RELIABILITY AB Introduction: The Myotonic Dystrophy Health Index (MDHI) is a disease-specific patient-reported outcome measure. Here, we examine the associations between the MDHI and other measures of disease burden in a cohort of individuals with myotonic dystrophy type-1 (DM1). Methods: We conducted a cross-sectional study of 70 patients with DM1. We examined the associations between MDHI total and subscale scores and scores from other clinical tests. Participants completed assessments of strength, myotonia, motor and respiratory function, ambulation, and body composition. Participants also provided blood samples, underwent physician evaluations, and completed other patient-reported outcome measures. Results: MDHI total and subscale scores were strongly associated with muscle strength, myotonia, motor function, and other clinical measures. Conclusions: Patient-reported health status, as measured by the MDHI, is associated with alternative measures of clinical health. These results support the use of the MDHI as a valid tool to measure disease burden in DM1 patients. C1 [Heatwole, Chad; Dekdebrun, Jeanne; Dilek, Nuran; Eichinger, Katy; Hilbert, James E.; Logigian, Eric; Luebbe, Elizabeth; Martens, William; Mcdermott, Michael P.; Pandya, Shree; Thornton, Charles; Moxley, Richard T., III] Univ Rochester, Med Ctr, Dept Neurol, 601 Elmwood Ave,Box 673, Rochester, NY 14642 USA. [Bode, Rita] Psychometr Consultant, Chicago, IL USA. [Johnson, Nicholas E.] Univ Utah, Salt Lake City, UT USA. [Mcdermott, Michael P.] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. [Puwanant, Araya] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Rothrock, Nan; Victorson, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Vickrey, Barbara G.] Univ Calif Los Angeles, David Geffen Sch Med, Med Ctr, Los Angeles, CA 90095 USA. [Vickrey, Barbara G.] Greater Los Angeles VA HealthCare Syst, Los Angeles, CA USA. RP Heatwole, C (reprint author), Univ Rochester, Med Ctr, Dept Neurol, 601 Elmwood Ave,Box 673, Rochester, NY 14642 USA. EM chad_heatwole@urmc.rochester.edu FU Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center [NINDS U54NS48843]; Muscular Dystrophy Association; Saunders Family Fund; Abrams Family Fund for Myotonic Dystrophy Research; University of Rochester CTSA award from the National Center for Research Resources [UL1 RR024160]; National Center for Advancing Translational Sciences of the National Institutes of Health FX Support for this research was provided by the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center (NINDS U54NS48843), the Muscular Dystrophy Association, the Saunders Family Fund, and the Abrams Family Fund for Myotonic Dystrophy Research. The project described in this publication was also supported by the University of Rochester CTSA award number UL1 RR024160 from the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional information regarding the MDHI is available at the Neuromuscular Institute of Quality-of-Life Studies and Outcome Measure Development website www.QOLINSTITUTE.com and MDHI licensing opportunities can be reviewed at: www.urmc.rochester.edu/techtransfer. NR 47 TC 2 Z9 2 U1 1 U2 3 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 FEB PY 2016 VL 53 IS 2 BP 183 EP 190 DI 10.1002/mus.24725 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DD3RE UT WOS:000369839500003 PM 26044513 ER PT J AU Doench, JG Fusi, N Sullender, M Hegde, M Vaimberg, EW Donovan, KF Smith, I Tothova, Z Wilen, C Orchard, R Virgin, HW Listgarten, J Root, DE AF Doench, John G. Fusi, Nicolo Sullender, Meagan Hegde, Mudra Vaimberg, Emma W. Donovan, Katherine F. Smith, Ian Tothova, Zuzana Wilen, Craig Orchard, Robert Virgin, Herbert W. Listgarten, Jennifer Root, David E. TI Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9 SO NATURE BIOTECHNOLOGY LA English DT Article ID HUMAN-CELLS; FUNCTIONAL GENOMICS; GENETIC SCREENS; RAF INHIBITION; CAS NUCLEASES; RNA; DNA; IDENTIFICATION; SPECIFICITY; SYSTEMS AB CRISPR-Cas9-based genetic screens are a powerful new tool in biology. By simply altering the sequence of the single-guide RNA (sgRNA), one can reprogram Cas9 to target different sites in the genome with relative ease, but the on-target activity and off-target effects of individual sgRNAs can vary widely. Here, we use recently devised sgRNA design rules to create human and mouse genome-wide libraries, perform positive and negative selection screens and observe that the use of these rules produced improved results. Additionally, we profile the off-target activity of thousands of sgRNAs and develop a metric to predict off-target sites. We incorporate these findings from large-scale, empirical data to improve our computational design rules and create optimized sgRNA libraries that maximize on-target activity and minimize off-target effects to enable more effective and efficient genetic screens and genome engineering. C1 [Doench, John G.; Sullender, Meagan; Hegde, Mudra; Vaimberg, Emma W.; Donovan, Katherine F.; Smith, Ian; Tothova, Zuzana; Root, David E.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Fusi, Nicolo; Listgarten, Jennifer] Microsoft Res New England, Cambridge, MA USA. [Tothova, Zuzana] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Wilen, Craig; Orchard, Robert; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. RP Doench, JG; Root, DE (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA.; Fusi, N; Listgarten, J (reprint author), Microsoft Res New England, Cambridge, MA USA. EM jdoench@broadinstitute.org; fusi@microsoft.com; jennl@microsoft.com; droot@broadinstitute.org OI Sullender, Meagan/0000-0001-6666-8650; Wilen, Craig/0000-0003-2495-9403 FU NIH [5K12CA087723-12]; ASCO Young Investigator Award; LLS Special Fellow Award; Next Generation Fund at the Broad Institute of MIT and Harvard FX We thank M. Tomko, M. Greene, A. Brown, D. Alan and T. Green for software engineering support, and T. Nguyen, N. Tran and X. Yang for library production support (Broad Institute). Z.T. is funded by NIH 5K12CA087723-12, ASCO Young Investigator Award, LLS Special Fellow Award. J.G.D. is a Merkin Institute Fellow and is supported by the Next Generation Fund at the Broad Institute of MIT and Harvard. NR 53 TC 68 Z9 71 U1 47 U2 100 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 FEB PY 2016 VL 34 IS 2 BP 184 EP + DI 10.1038/nbt.3437 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DD0OK UT WOS:000369619100021 PM 26780180 ER PT J AU Cristofaro, V Carey, SD Yalla, SV Sullivan, MP AF Cristofaro, Vivian Carey, Sean D. Yalla, Subbarao V. Sullivan, Maryrose P. TI CAVEOLAE-MEDIATED REGULATION OF ALPHA-1-ADRENOCEPTOR SUBTYPES IN OVERACTIVE BLADDERS FROM SPONTANEOUSLY HYPERTENSIVE RATS SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-of-Urodynamics-Female-Pelvic-Medicine-and-Urogenital-Reconstruct ion CY FEB 23-27, 2016 CL New Orleans, LA SP Soc Urodynam Female Pelv Med & Urogenital Reconstruct C1 [Cristofaro, Vivian; Carey, Sean D.; Yalla, Subbarao V.; Sullivan, Maryrose P.] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 EI 1520-6777 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2016 VL 35 SU 1 MA BS31 BP S19 EP S19 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA DD2BF UT WOS:000369726700033 ER PT J AU Doyle, C Chung, YG Schafer, M Sack, B Costa, K Cristofaro, V Sullivan, MP Adam, RM AF Doyle, Claire Chung, Yeun Goo Schaefer, Mattias Sack, Bryan Costa, Kyle Cristofaro, Vivian Sullivan, Maryrose P. Adam, Rosalyn M. TI INOSINE ATTENUATES SPONTANEOUS AND EVOKED ACTIVITY IN NEUROGENIC BLADDER THROUGH AN ADENOSINE RECEPTOR-MEDIATED PATHWAY SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-of-Urodynamics-Female-Pelvic-Medicine-and-Urogenital-Reconstruct ion CY FEB 23-27, 2016 CL New Orleans, LA SP Soc Urodynam Female Pelv Med & Urogenital Reconstruct C1 [Doyle, Claire; Chung, Yeun Goo; Schaefer, Mattias; Sack, Bryan; Costa, Kyle; Adam, Rosalyn M.] Boston Childrens Hosp, Boston, MA USA. [Doyle, Claire; Chung, Yeun Goo; Schaefer, Mattias; Sack, Bryan; Cristofaro, Vivian; Sullivan, Maryrose P.; Adam, Rosalyn M.] Harvard Univ, Sch Med, Boston, MA USA. [Cristofaro, Vivian; Sullivan, Maryrose P.] VA Boston Healthcare Syst, West Roxbury, 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 0733-2467 EI 1520-6777 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2016 VL 35 SU 1 MA BS18 BP S14 EP S14 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA DD2BF UT WOS:000369726700020 ER PT J AU Hess, D Raup, V Hanske, J Ozambela, M Schmid, M Thurmond, P Varda, B Trinh, QD Eswara, J AF Hess, Deborah Raup, Valary Hanske, Julian Ozambela, Manuel Schmid, Marianne Thurmond, Portia Varda, Briony Quoc-Dien Trinh Eswara, Jairam TI PERIOPERATIVE OUTCOMES OF VESICOVAGINAL FISTULA REPAIR: VAGINAL VERSUS ABDOMINAL SURGICAL APPROACH SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-of-Urodynamics-Female-Pelvic-Medicine-and-Urogenital-Reconstruct ion CY FEB 23-27, 2016 CL New Orleans, LA SP Soc Urodynam Female Pelv Med & Urogenital Reconstruct C1 [Hess, Deborah; Raup, Valary; Ozambela, Manuel; Varda, Briony; Quoc-Dien Trinh; Eswara, Jairam] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hanske, Julian] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Schmid, Marianne] Ruhr Univ Bochum, Herne, Germany. [Thurmond, Portia] VA Boston Healthcare Syst, West Roxbury, 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 0733-2467 EI 1520-6777 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2016 VL 35 SU 1 MA NM122 BP S89 EP S89 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA DD2BF UT WOS:000369726700219 ER PT J AU Kreydin, EI Kim, MM Oliver, JL Cohen, SA Ackerman, AL Kim, JH Raz, S AF Kreydin, Evgeniy I. Kim, Michelle M. Oliver, Janine L. Cohen, Seth A. Ackerman, A. Lenore Kim, Ja-Hong Raz, Shlomo TI HIGHER URINE LEVELS OF ENVIRONMENTAL TOXINS ARE ASSOCIATED WITH INCREASED INCONTINENCE AND NOCTURIA IN MEN SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-of-Urodynamics-Female-Pelvic-Medicine-and-Urogenital-Reconstruct ion CY FEB 23-27, 2016 CL New Orleans, LA SP Soc Urodynam Female Pelv Med & Urogenital Reconstruct C1 [Kreydin, Evgeniy I.; Oliver, Janine L.; Cohen, Seth A.; Ackerman, A. Lenore; Kim, Ja-Hong; Raz, Shlomo] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kim, Michelle M.] 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 0733-2467 EI 1520-6777 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2016 VL 35 SU 1 MA NM15 BP S51 EP S51 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA DD2BF UT WOS:000369726700117 ER PT J AU Kreydin, EI Oliver, JL Kim, MM Ackerman, AL Cohen, SA Kim, JH Raz, S AF Kreydin, Evgeniy I. Oliver, Janine L. Kim, Michelle M. Ackerman, A. Lenore Cohen, Seth A. Kim, Ja-Hong Raz, Shlomo TI 'TIL DEATH DO US PART: THE RELATIONSHIP BETWEEN URINARY INCONTINENCE AND MARITAL STATUS AMONG US WOMEN AND MEN SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-of-Urodynamics-Female-Pelvic-Medicine-and-Urogenital-Reconstruct ion CY FEB 23-27, 2016 CL New Orleans, LA SP Soc Urodynam Female Pelv Med & Urogenital Reconstruct C1 [Kreydin, Evgeniy I.; Oliver, Janine L.; Ackerman, A. Lenore; Cohen, Seth A.; Kim, Ja-Hong; Raz, Shlomo] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kim, Michelle M.] 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 0733-2467 EI 1520-6777 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2016 VL 35 SU 1 MA NM14 BP S51 EP S51 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA DD2BF UT WOS:000369726700116 ER PT J AU Vasquez, E Bielenberg, D Cristofaro, V Sullivan, M Adam, R AF Vasquez, Evalynn Bielenberg, Diane Cristofaro, Vivian Sullivan, Maryrose Adam, Rosalyn TI NEUROPILIN 2 DELETION ENHANCES DETRUSOR CONTRACTILITY UNDER CONDITIONS OF BLADDER OUTLET OBSTRUCTION SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Winter Meeting of the Society-of-Urodynamics-Female-Pelvic-Medicine-and-Urogenital-Reconstruct ion CY FEB 23-27, 2016 CL New Orleans, LA SP Soc Urodynam Female Pelv Med & Urogenital Reconstruct C1 [Vasquez, Evalynn; Bielenberg, Diane; Adam, Rosalyn] Boston Childrens Hosp, Boston, MA USA. [Vasquez, Evalynn; Bielenberg, Diane] Harvard Univ, Sch Med, Boston, MA USA. [Cristofaro, Vivian; Sullivan, Maryrose] VA Boston Healthcare Syst, West Roxbury, MA USA. [Cristofaro, Vivian; Sullivan, Maryrose] Harvard Univ, Sch Med, West Roxbury, MA USA. [Adam, Rosalyn] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 EI 1520-6777 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD FEB PY 2016 VL 35 SU 1 MA BS25 BP S16 EP S17 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA DD2BF UT WOS:000369726700027 ER PT J AU Jena, AB Khullar, D Ho, O Olenski, AR Blumenthal, DM AF Jena, Anupam B. Khullar, Dhruv Ho, Oliver Olenski, Andrew R. Blumenthal, Daniel M. TI Sex Differences in Academic Rank in US Medical Schools in 2014 SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material ID PHYSICIAN-RESEARCHERS; GENDER-DIFFERENCES AB The number of women entering medical schools in the United States has increased to the point where women make up half of all US graduates. However, sex disparities exist in senior faculty rank. Female physician researchers also earn less than do their male counterparts, even when adjusted for differences in academic productivity. Previous studies on this topic have several limitations, and none have considered these data along with factors such as experience, research funding, scientific authorship, and physician training. This study hypothesized that after adjustment for several factors-sex, age, years since residency completion, specialty, National Institutes of Health (NIH) research funding, scientific authorship, and clinical trial participation-sex differences in faculty rank would still exist. A cross-sectional database of 1,005,419 physicians in the United States in 2014 was used to collect information. For each physician, data were assembled using NIH RePORT, PubMed, and ClinicalTrials.gov. Some of this information was self-verified by registered members, whereas some was supplied by institutions. The subgroup of registered members was analyzed first as those data were likely more accurate. Then, data on faculty rank, PubMed publications, clinical trial participation, and NIH funding weremanually confirmed for a random sample of 200. The data were analyzed using a multivariable logistic model to estimate the probability of full professorship as a function of the factors listed in the hypothesis. A subgroup was analyzed to compare differences in full professorship according to specialty and medical school research ranking (schools listed as top 20 in the United States according to US News & World Report in 2013 vs those not listed as top 20). A total of 91,073 faculty members were included in the study. Of those, 66.5% were men. Compared with men, women were less likely to be full professors (11.9% [3623 of 30,464] vs 28.6% [17354 of 60,609]; absolute difference, -16.7%; 95% confidence interval [CI], -17.3% to -16.2%). Women tended to be specialized in internal medicine, obstetrics and gynecology, and pediatrics, on average, and were also younger and more recently completed residency. Representation of women at top 20 versus not top-ranked schools was similar (29.2% [8893 of 30,464] vs 28.3% [17,173 of 60,609]; difference, 0.9%; 95% CI, 0.7%-1.1%). Women were less likely than men to have conducted clinical trials (6.4% vs 8.8%; difference, -2.4% CI, -2.8% to 2.0%) and were also less likely to have NIH funding (6.8% vs 10.3%, difference, -3.5%; 95% CI, -2.8% to 2.0%). Women also had fewer first-or last-author publications than did their male peers (mean total, 11.6 vs 24.8, difference, -13.2; 95% CI, -13.6 to -12.7; mean first-or last-author publication; 5.9 vs 13.7; difference, -7.8; 95% CI, -8.1 to -7.5). Women were less likely to be full professor or associate or full professor by 2014 in 3 residency cohorts (1980, 1990, and 2000), and among faculty who were associate or full professor in 2014, fewer women than men were full professor across all cohorts. After accounting for age, experience, specialty, and measures of research productivity, women were substantially less likely to be full professors in US medical schools. This study was limited by a number of factors, among those, the fact that it did not account for other leadership roles or administrative positions outside academic rank and did not account for sex differences in promotion. C1 [Jena, Anupam B.; Ho, Oliver; Olenski, Andrew R.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Khullar, Dhruv] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Khullar, Dhruv; Blumenthal, Daniel M.] Harvard Univ, Sch Med, Boston, MA USA. [Blumenthal, Daniel M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.; Jena, AB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Jena, AB (reprint author), Natl Bur Econ Res, Cambridge, MA 02138 USA. NR 7 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 FEB PY 2016 VL 71 IS 2 BP 61 EP 62 DI 10.1097/01.ogx.0000480221.58767.1a PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DD4DW UT WOS:000369873700001 ER PT J AU Dimitriou, D Tsai, TY Yue, B Rubash, HE Kwon, YM Li, G AF Dimitriou, D. Tsai, T. -Y. Yue, B. Rubash, H. E. Kwon, Y. -M. Li, G. TI Side-to-side variation in normal femoral morphology: 3D CT analysis of 122 femurs SO ORTHOPAEDICS & TRAUMATOLOGY-SURGERY & RESEARCH LA English DT Article DE Proximal femur; Asymmetry; Total hip arthroplasty; Offset; Anteversion; Hip joint center; Geommetric morphometrics ID TOTAL HIP-ARTHROPLASTY; JOINT; ANTEVERSION; ACCURACY; SYMMETRY AB Background: The contralateral femur is often used as reference for reconstruction in unilateral hip joint pathology. The objective of this study was to quantify the side-to-side variation in proximal femur. We hypothesized that significant side-to-side differences exist between left and right femur with implications for preoperative planning and leg length discrepancy following hip arthroplasty. Materials and methods: CT-based 3D femoral models were reconstructed for 122 paired femurs in 61 young healthy subjects (46.9 +/- 6.8 years) with no history of hip pathology. Side-to-side differences of several femoral morphologic parameters, including femoral head diameter, femoral anteversion, horizontal offset and femoral head center location, were compared and correlated with demographic factors using multiple linear regression. Results: Significant side-to-side differences (P < 0.01) were found in femoral anteversion (4.3 +/- 3.8 degrees; range: 0.2 degrees to 17.3 degrees), horizontal offset (2.5 +/- 2.1 mm; range: 0.1 to 10.3 mm), and femoral head center location (7.1 +/- 3.8 mm; range: 0.5 to 19.4 mm). The difference in femoral anteversion was strongly correlated with the difference in neck diameter (R-2 = 0.79), whereas the difference in horizontal femoral offset was highly correlated with the head diameter difference (R-2 = 0.72). Femoral head center difference was correlated with the femoral anteversion, horizontal offset and neck-shaft-angle difference (R-2 = 0.82). Discussion: Relying on the anatomic landmarks of the contralateral femur during hip arthroplasty may not necessarily result in restoration of native anatomy and leg-length. Knowledge of the baseline side-to-side asymmetry could provide a range of error that would be tolerable following hip reconstruction. Level of evidence: Level IV. Type of study: Retrospective observational study. (C) 2015 Elsevier Masson SAS. All rights reserved. C1 [Dimitriou, D.; Tsai, T. -Y.; Rubash, H. E.; Kwon, Y. -M.; Li, G.] Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab,Med Sch Boston, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. [Yue, B.] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Orthoped, Shanghai 200030, Peoples R China. RP Li, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab,Med Sch Boston, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@mgh.harvard.edu OI Dimitriou, Dimitris/0000-0002-9558-7080 NR 20 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 1877-0568 J9 ORTHOP TRAUMATOL-SUR JI Orthop. Traumatol.-Surg. Res. PD FEB PY 2016 VL 102 IS 1 BP 91 EP 97 DI 10.1016/j.otsr.2015.11.004 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DD6WC UT WOS:000370064300015 PM 26867707 ER PT J AU Jemielita, TO Leonard, MB Baker, J Sayed, S Zemel, BS Shults, J Herskovitz, R Denburg, MR AF Jemielita, T. O. Leonard, M. B. Baker, J. Sayed, S. Zemel, B. S. Shults, J. Herskovitz, R. Denburg, M. R. TI Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone mineral density; Parathyroid hormone; Vitamin D; Vitamin D-binding protein ID RANDOMIZED-CONTROLLED-TRIALS; NUTRITION EXAMINATION SURVEY; D SUPPLEMENTATION; AFRICAN-AMERICAN; WHITE WOMEN; SERUM 25-HYDROXYVITAMIN-D; FRACTURE PREVENTION; NATIONAL-HEALTH; CALCIUM; MEN AB A comparison of the association of different forms of 25-hydroxyvitamin D [25(OH)D] with parathyroid hormone (PTH) and with areal and volumetric bone mineral density (BMD) demonstrated that bioavailable and free 25(OH)D do not provide a better index of vitamin D status in terms of bone health compared to total 25(OH)D. Introduction This study aims to compare measures of vitamin D-binding protein (DBP) using a monoclonal versus polyclonal ELISA and assess correlations of total versus estimated free and bioavailable 25(OH)D with BMD and PTH concentrations. Methods DXA and peripheral quantitative CT (pQCT) scans were obtained in 304 adults (158 black, 146 white), ages 21-80 years. Free and bioavailable 25(OH)D were calculated from total 25(OH)D, DBP, and albumin concentrations. Multivariable linear regression with standardized beta coefficients was used to evaluate associations of bone measures and PTH with total, free, and bioavailable 25(OH)D. Results Measures of DBP obtained using a monoclonal versus polyclonal ELISA were not correlated (r (s) = 0.02, p = 0.76). Free and bioavailable 25(OH)D based on the polyclonal assay were lower in black versus white participants (p < 0.0001); this race difference was not evident using the monoclonal assay. Adjusted for age, sex, calcium intake, and race, all forms of 25(OH)D were negatively associated with PTH, but the absolute coefficient was greatest for total 25(OH)D (-0.34, p < 0.001) versus free/bioavailable 25(OH)D (-0.18/-0.24 depending on DBP assay, p <= 0.003). In analyses stratified on race, none of the measures of 25(OH)D were associated with BMD across DXA and pQCT sites. Conclusions The monoclonal versus polyclonal ELISA yielded highly discrepant measures of DBP, particularly among black individuals, likely related to established race differences in DBP polymorphisms. Contrary to prior studies, our findings indicate that using DBP to estimate bioavailable and free 25(OH)D does not provide a better index of vitamin D status in terms of bone health. C1 [Jemielita, T. O.; Baker, J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Leonard, M. B.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Baker, J.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Sayed, S.; Herskovitz, R.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Zemel, B. S.; Shults, J.; Denburg, M. R.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. RP Denburg, MR (reprint author), Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM denburgm@email.chop.edu FU NIH [K23 DK093556, K24 DK076808, R01DK064966, T32DK060455]; Nephcure Foundation-American Society of Nephrology Research Grant; Veterans Affairs Clinical Science Research & Development Career Development Award FX This project was supported by NIH Grants K23 DK093556 (MRD), K24 DK076808 (MBL and JS), R01DK064966 (MBL), and T32DK060455 (TJ). Dr. Denburg was also funded by The Nephcure Foundation-American Society of Nephrology Research Grant. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr. Baker is supported by a Veterans Affairs Clinical Science Research & Development Career Development Award. The contents of this work do not represent the views of the Department of Veterans Affairs or the United States Government. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript. NR 53 TC 7 Z9 7 U1 1 U2 4 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD FEB PY 2016 VL 27 IS 2 BP 617 EP 626 DI 10.1007/s00198-015-3296-6 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD6PN UT WOS:000370046200020 PM 26359185 ER PT J AU Kaplan, AB Kozin, ED Remenschneider, A Eftekhari, K Jung, DH Polley, DB Lee, DJ AF Kaplan, Alyson B. Kozin, Elliott D. Remenschneider, Aaron Eftekhari, Kian Jung, David H. Polley, Daniel B. Lee, Daniel J. TI Amblyaudia: Review of Pathophysiology, Clinical Presentation, and Treatment of a New Diagnosis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Review DE amblyaudia; conductive hearing loss; amblyopia; congenital hearing loss ID CONDUCTIVE HEARING-LOSS; CHRONIC OTITIS-MEDIA; BILATERAL COCHLEAR IMPLANTS; STEM AUDITORY NUCLEI; ACTION VIDEO GAME; QUALITY-OF-LIFE; SOUND LOCALIZATION; BINAURAL HEARING; BINOCULAR VISION; SENSITIVE PERIOD AB Objective Similar to amblyopia in the visual system, amblyaudia is a term used to describe persistent hearing difficulty experienced by individuals with a history of asymmetric hearing loss (AHL) during a critical window of brain development. Few clinical reports have described this phenomenon and its consequent effects on central auditory processing. We aim to (1) define the concept of amblyaudia and (2) review contemporary research on its pathophysiology and emerging clinical relevance. Data Sources PubMed, Embase, and Cochrane databases. Review Methods A systematic literature search was performed with combinations of search terms: amblyaudia, conductive hearing loss, sensorineural hearing loss, asymmetric, pediatric, auditory deprivation, and auditory development. Relevant articles were considered for inclusion, including basic and clinical studies, case series, and major reviews. Conclusions During critical periods of infant brain development, imbalanced auditory input associated with AHL may lead to abnormalities in binaural processing. Patients with amblyaudia can demonstrate long-term deficits in auditory perception even with correction or resolution of AHL. The greatest impact is in sound localization and hearing in noisy environments, both of which rely on bilateral auditory cues. Diagnosis and quantification of amblyaudia remain controversial and poorly defined. Prevention of amblyaudia may be possible through early identification and timely management of reversible causes of AHL. Implications for Practice Otolaryngologists, audiologists, and pediatricians should be aware of emerging data supporting amblyaudia as a diagnostic entity and be cognizant of the potential for lasting consequences of AHL. Prevention of long-term auditory deficits may be possible through rapid identification and correction. C1 [Kaplan, Alyson B.; Kozin, Elliott D.; Remenschneider, Aaron; Jung, David H.; Polley, Daniel B.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kaplan, Alyson B.; Kozin, Elliott D.; Remenschneider, Aaron; Jung, David H.; Polley, Daniel B.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Eftekhari, Kian] Oculoplast Surg Inc, Salt Lake City, UT USA. RP Kozin, ED (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM Elliott_Kozin@meei.harvard.edu OI Polley, Daniel/0000-0002-5120-2409 FU NIDCD NIH HHS [R01 DC009836] NR 99 TC 3 Z9 3 U1 6 U2 8 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 FEB PY 2016 VL 154 IS 2 BP 247 EP 255 DI 10.1177/0194599815615871 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DD5VB UT WOS:000369991600008 PM 26556464 ER PT J AU McMains, KC AF McMains, Kevin Christopher TI Response to "A Beacon of Emotional Resilience in a Storm of Mistreatment?" SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Letter C1 [McMains, Kevin Christopher] South Texas Vet Hlth Care Syst, Surg, San Antonio, TX USA. RP McMains, KC (reprint author), South Texas Vet Hlth Care Syst, Surg, San Antonio, TX USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 2016 VL 154 IS 2 BP 398 EP 399 DI 10.1177/0194599815621529 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DD5VB UT WOS:000369991600035 PM 26833650 ER PT J AU Bicket, MC Hanna, GM AF Bicket, Mark C. Hanna, George M. TI Intrathecal Pump Exposure to Electromagnetic Interference: A Report of Device Interrogation following Multiple ECT Sessions SO PAIN PHYSICIAN LA English DT Article DE Baclofen; intrathecal drug delivery system; electromagnetic interference; electroconvulsive therapy; safety; pump interrogation; intrathecal pump; pump stall ID DRUG-DELIVERY; SAFETY AB Background: Intrathecal drug delivery systems represent an increasingly common treatment modality for patients with a variety of conditions, including chronic pain and spasticity. Pumps rely on electronic programming to properly control and administer highly concentrated medications. Electromagnetic interference (EMI) is a known exposure that may cause a potential patient safety issue stemming from direct patient injury, pump damage, or changes to pump operation or flow rate. Objectives: The objective of our case report was to describe an approach to evaluating a patient with a pump prior to and following exposure to EMI from electroconvulsive therapy (ECT), as well as to document findings from device interrogations associated with this event. Study Design: Case report. Setting: Academic university-based pain management center. Results: We present the case of a patient with an intrathecal pump who underwent multiple exposures to EMI in the form of 42 ECT sessions. Interrogation of the intrathecal drug delivery system revealed no safety issues following ECT sessions. At no time were error messages, unintentional changes in event logs, unintentional changes in pump settings, or evidence of pump stall or over-infusion noted. Conclusion: Communication with multiple entities (patient, family, consulting physicians, and device manufacturer) and maintaining vigilance through device interrogation both before and after EMI exposure are appropriate safeguards to mitigate the risk and detect potential adverse events of EMI with intrathecal drug delivery systems. Given the infrequent reports of device exposure to ECT, best practices may be derived from experience with EMI exposure from magnetic resonance imaging (MRI). Although routine EMI exposure to intrathecal drug delivery systems should be avoided, we describe one patient with repeated exposure to ECT without apparent complication. C1 [Bicket, Mark C.; Hanna, George M.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. RP Bicket, MC (reprint author), Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, 600 N Wolfe St, Baltimore, MD 21287 USA. EM bicket@jhmi.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD FEB PY 2016 VL 19 IS 2 BP E343 EP E345 PG 3 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA DC1QI UT WOS:000368991000009 PM 26815262 ER PT J AU Lai, ECC Hsieh, CY Wong, MB Lin, SJ Yang, YK Yang, YHK Setoguchi, S AF Lai, Edward Chia-Cheng Hsieh, Cheng-Yang Wong, Monera B. Lin, Swu-Jane Yang, Yang-Kuang Yang, Yea-Huei Kao Setoguchi, Soko TI Comparative risk of oral ulcerations among antipsychotics users - population-based retrospective cohort study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE antipsychotics; schizophrenia; oral health; aripiprazole; sulpiride; olanzapine; quetiapine; pharmacoepidemiology ID INDUCED SIALORRHEA; PHYSICAL-ACTIVITIES; OLDER-ADULTS; DRY MOUTH; HEALTH; PREVALENCE; SCHIZOPHRENIA; OUTPATIENTS; XEROSTOMIA; MEDICATION AB PurposeThe study aimed to evaluate the comparative risk of oral ulcerations among antipsychotic medications. MethodsWe analyzed the National Health Insurance Research Database of Taiwan and included patients newly initiated with a single antipsychotic agent including haloperidol, sulpiride, olanzapine, quetiapine, risperidone, or amisulpride during 2002 to 2010. The outcome of interest was oral ulceration, defined by the presence diagnoses of stomatitis and mucositis, aphthous-like ulceration and oral burns, or dispensing of stomatological corticosteroids included triamcinolone, dexamethasone, hydrocortisone, and prednisolone. We conducted Cox proportional hazards regression to compare the risks of oral ulceration among antipsychotics. ResultsThe rate of oral ulcerations was highest in the amisulpride group (217.7 per 1000 person-year), followed by quetiapine (193.9 per 1000 person-year), olanzapine (161.9 per 1000 person-year), sulpiride (147.1 per 1000 person-year), risperidone (115.6 per 1000 person-year), haloperidol (107.5 per 1000 person-year) and aripiprazole (49.8 per 1000 person-year). Compared with haloperidol users, the adjusted hazard ratio (AHR) was 1.40 (95% CI, 1.12-1.73) in olanzapine, 1.48 (95% CI, 1.30-1.69) in quetiapine, 1.27 (95% CI, 1.19-1.44) in sulpiride, 1.68 (95% CI, 0.97-2.59) in amisulpride, 1.02 (95% CI, 0.83-1.45) in risperidone, and 0.41 (95% CI, 0.24-0.72) in aripiprazole users by Cox regression model. ConclusionOlanzapine, quetiapine, and sulpiride posed a higher risk, while aripiprazole posed a lower risk of oral ulcerations compared with haloperidol in subjects with newly initiated antipsychotic therapy. Risperidone and amisulpride tended to have higher risk of oral ulcerations, but this was not statistically significant. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Lai, Edward Chia-Cheng; Setoguchi, Soko] Duke Clin Res Inst, Durham, NC USA. [Lai, Edward Chia-Cheng; Setoguchi, Soko] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Lai, Edward Chia-Cheng; Hsieh, Cheng-Yang; Yang, Yea-Huei Kao] Natl Cheng Kung Univ, Sch Pharm, Tainan 701, Taiwan. [Lai, Edward Chia-Cheng; Hsieh, Cheng-Yang; Yang, Yea-Huei Kao] Natl Cheng Kung Univ, Inst Clin Pharm & Pharmaceut Sci, Tainan 701, Taiwan. [Lai, Edward Chia-Cheng; Yang, Yea-Huei Kao] Natl Cheng Kung Univ, Hlth Outcome Res Ctr, Tainan 701, Taiwan. [Hsieh, Cheng-Yang] Tainan Sin Lau Hosp, Dept Neurol, Tainan, Taiwan. [Wong, Monera B.] Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA. [Lin, Swu-Jane] Univ Illinois, Coll Pharm, Dept Pharm Adm, Chicago, IL USA. [Yang, Yang-Kuang] Natl Cheng Kung Univ Hosp, Dept Psychiat, Tainan 70428, Taiwan. [Yang, Yang-Kuang] Natl Cheng Kung Univ, Coll Med, Tainan 70101, Taiwan. RP Yang, YHK (reprint author), Natl Cheng Kung Univ, Sch Pharm, Coll Med, 1 Univ Rd, Tainan 701, Taiwan.; Yang, YHK (reprint author), Natl Cheng Kung Univ, Inst Clin Pharm & Pharmaceut Sci, Coll Med, 1 Univ Rd, Tainan 701, Taiwan. EM yhkao@mail.ncku.edu.tw NR 43 TC 0 Z9 0 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD FEB PY 2016 VL 25 IS 2 BP 123 EP 132 DI 10.1002/pds.3903 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD6TA UT WOS:000370056200002 PM 26549190 ER PT J AU Axon, RN Cole, L Moonan, A Foster, R Cawley, P Long, L Turley, CB AF Axon, R. Neal Cole, Laura Moonan, Aunyika Foster, Richard Cawley, Patrick Long, Laura Turley, Christine B. TI Evolution and Initial Experience of a Statewide Care Transitions Quality Improvement Collaborative: Preventing Avoidable Readmissions Together SO POPULATION HEALTH MANAGEMENT LA English DT Article ID HOSPITAL READMISSION; HEART-FAILURE; REHOSPITALIZATIONS; RISK AB Increasing scrutiny of hospital readmission rates has spurred a wide variety of quality improvement initiatives. The Preventing Avoidable Readmissions Together (PART) initiative is a statewide quality improvement learning collaborative organized by stakeholder organizations in South Carolina. This descriptive report focused on initial interventions with hospitals. Eligible participants included all acute care hospitals plus home health organizations, nursing facilities, hospices, and other health care organizations. Measures were degree of statewide participation, curricular engagement, adoption of evidence-based improvement strategies, and readmission rate changes. Fifty-nine of 64 (92%) acute care hospitals and 9 of 10 (90%) hospital systems participated in collaborative events. Curricular engagement included: webinars and coaching calls (49/59, 83%), statewide in-person meetings (35/59, 59%), regional in-person meetings (44/59, 75%), and individualized consultations (46/59, 78%). Among 34 (58%) participating hospitals completing a survey at the completion of Year 1, respondents indicated complete implementation of multidisciplinary rounding (58%), post-discharge telephone calls (58%), and teach-back (32%), and implementation in process of high-quality transition records (52%), improved discharge summaries (45%), and timely follow-up appointments (39%). A higher proportion of hospitals had significant decreases (10% relative change) in all-cause readmission rates for acute myocardial infarction (55.6% vs. 30.4%, P=0.01), heart failure (54.2% vs. 31.7%, P=0.09), and chronic obstructive pulmonary disease (41.7% vs. 33.3%, P=0.83) between 2011-2013 compared to earlier (2009-2011) trends. Focus on reducing readmissions is driving numerous, sometimes competing, quality improvement initiatives. PART successfully engaged the majority of acute care facilities in one state to harmonize and accelerate adoption of evidence-based care transitions strategies. (Population Health Management 2016;19:4-10) C1 [Axon, R. Neal] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Axon, R. Neal; Cawley, Patrick] Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. [Cole, Laura; Moonan, Aunyika; Foster, Richard] South Carolina Hosp Assoc, Columbia, SC USA. [Long, Laura] BlueCross BlueShield South Carolina, Columbia, SC USA. [Turley, Christine B.] Hlth Sci S Carolina, Columbia, SC USA. [Turley, Christine B.] Univ S Carolina, Sch Med, Columbia, SC USA. RP Axon, RN (reprint author), Ralph H Johnson VA Med Ctr, Charleston, SC USA.; Axon, RN (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA.; Axon, RN (reprint author), 109 Bee St,Mail Code 111, Charleston, SC 29401 USA. EM axon@musc.edu NR 19 TC 1 Z9 1 U1 4 U2 12 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1942-7891 EI 1942-7905 J9 POPUL HEALTH MANAG JI Popul. Health Manag. PD FEB 1 PY 2016 VL 19 IS 1 BP 4 EP 10 DI 10.1089/pop.2014.0182 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DD4DO UT WOS:000369872900002 PM 26102592 ER PT J AU Yu, LL Rodriguez, RA Chen, LL Chen, LY Perry, G McHardy, SF Yeh, CK AF Yu, Lili Rodriguez, Roberto A. Chen, L. Laurie Chen, Liao Y. Perry, George McHardy, Stanton F. Yeh, Chih-Ko TI 1,3-propanediol binds deep inside the channel to inhibit water permeation through aquaporins SO PROTEIN SCIENCE LA English DT Article DE ligand-protein interaction; aquaporin inhibitor; molecular dynamics ID X-RAY-STRUCTURE; NEPHROGENIC DIABETES-INSIPIDUS; PLASMODIUM-FALCIPARUM; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; FREE-ENERGY; BRAIN; MICE; AQUAGLYCEROPORIN; TRAFFICKING AB Aquaporins and aquaglyceroporins (AQPs) are membrane channel proteins responsible for transport of water and for transport of glycerol in addition to water across the cell membrane, respectively. They are expressed throughout the human body and also in other forms of life. Inhibitors of human AQPs have been sought for therapeutic treatment for various medical conditions including hypertension, refractory edema, neurotoxic brain edema, and so forth. Conducting all-atom molecular dynamics simulations, we computed the binding affinity of acetazolamide to human AQP4 that agrees closely with in vitro experiments. Using this validated computational method, we found that 1,3-propanediol (PDO) binds deep inside the AQP4 channel to inhibit that particular aquaporin efficaciously. Furthermore, we used the same method to compute the affinities of PDO binding to four other AQPs and one aquaglyceroporin whose atomic coordinates are available from the protein data bank (PDB). For bovine AQP1, human AQP2, AQP4, AQP5, and Plasmodium falciparum PfAQP whose structures were resolved with high resolution, we obtained definitive predictions on the PDO dissociation constant. For human AQP1 whose PDB coordinates are less accurate, we estimated the dissociation constant with a rather large error bar. Taking into account the fact that PDO is generally recognized as safe by the US FDA, we predict that PDO can be an effective diuretic which directly modulates water flow through the protein channels. It should be free from the serious side effects associated with other diuretics that change the hydro-homeostasis indirectly by altering the osmotic gradients. C1 [Yu, Lili; Rodriguez, Roberto A.; Chen, Liao Y.] Univ Texas San Antonio, Dept Phys, One UTSA Circle, San Antonio, TX 78249 USA. [Chen, L. Laurie] Univ Texas SW Med Ctr Dallas, Sch Med, Dallas, TX 75390 USA. [Perry, George] Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA. [McHardy, Stanton F.] Univ Texas San Antonio, Dept Chem, San Antonio, TX 78249 USA. [Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Yeh, Chih-Ko] South Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78229 USA. [Yu, Lili] Yancheng Vocat Inst Hlth Sci, Dept Lab Med, Yancheng 224006, Jiangsu, Peoples R China. RP Chen, LY (reprint author), Univ Texas San Antonio, Dept Phys, One UTSA Circle, San Antonio, TX 78249 USA. EM Liao.chen@utsa.edu RI Chen, Liao/B-8037-2009; Perry, George/A-8611-2009; OI Chen, Liao/0000-0003-1911-8634; Perry, George/0000-0002-6547-0172; Rodriguez, Roberto/0000-0002-3303-9564 FU NIH [GM 084834] FX Grant sponsor: NIH; Grant number: GM 084834. NR 62 TC 1 Z9 1 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD FEB PY 2016 VL 25 IS 2 BP 433 EP 441 DI 10.1002/pro.2832 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DD3JW UT WOS:000369819500012 PM 26481430 ER PT J AU Rasmussen, V Turnell, A Butow, P Juraskova, I Kirsten, L Wiener, L Patenaude, A Hoekstra-Weebers, J Grassi, L AF Rasmussen, Victoria Turnell, Adrienne Butow, Phyllis Juraskova, Ilona Kirsten, Laura Wiener, Lori Patenaude, Andrea Hoekstra-Weebers, Josette Grassi, Luigi CA IPOS Res Committee TI Burnout among psychosocial oncologists: an application and extension of the effort-reward imbalance model SO PSYCHO-ONCOLOGY LA English DT Article ID CAREER-SUSTAINING BEHAVIORS; SELF-REPORTED HEALTH; PROFESSIONAL PSYCHOLOGISTS; OVER-COMMITMENT; MENTAL-HEALTH; WORK; NURSES; OVERCOMMITMENT; STRESS AB ObjectivesBurnout is a significant problem among healthcare professionals working within the oncology setting. This study aimed to investigate predictors of emotional exhaustion (EE) and depersonalisation (DP) in psychosocial oncologists, through the application of the effort-reward imbalance (ERI) model with an additional focus on the role of meaningful work in the burnout process. MethodsPsychosocial oncology clinicians (n=417) in direct patient contact who were proficient in English were recruited from 10 international psychosocial oncology societies. Participants completed an online questionnaire, which included measures of demographic and work characteristics, EE and DP subscales of the Maslach Burnout Inventory-Human Services Survey, the Short Version ERI Questionnaire and the Work and Meaning Inventory. ResultsHigher effort and lower reward were both significantly associated with greater EE, although not DP. The interaction of higher effort and lower reward did not predict greater EE or DP. Overcommitment predicted both EE and DP but did not moderate the impact of effort and reward on burnout. Overall, the ERI model accounted for 33% of the variance in EE. Meaningful work significantly predicted both EE and DP but accounted for only 2% more of the variance in EE above and beyond the ERI model. ConclusionsThe ERI was only partially supported as a useful framework for investigating burnout in psychosocial oncology professionals. Meaningful work may be a viable extension of the ERI model. Burnout among health professionals may be reduced by interventions aimed at increasing self-efficacy and changes to the supportive work environment. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Rasmussen, Victoria; Turnell, Adrienne; Butow, Phyllis; Juraskova, Ilona] Univ Sydney, Sch Psychol, Level 6 North,Lifehouse C39Z, Sydney, NSW 2006, Australia. [Butow, Phyllis; Juraskova, Ilona; Kirsten, Laura] Univ Sydney, Sch Psychol, Ctr Med Psychol & Evidence Based Decis Making CeM, Sydney, NSW 2006, Australia. [Butow, Phyllis] Univ Sydney, Psychooncol Cooperat Res Grp PoCoG, Sydney, NSW 2006, Australia. [Kirsten, Laura] Sydney West Canc Network, Nepean Canc Care Ctr, Westmead, NSW, Australia. [Wiener, Lori] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Patenaude, Andrea] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hoekstra-Weebers, Josette] Univ Groningen, Univ Med Ctr, Wenckebach Inst, Groningen, Netherlands. [Grassi, Luigi] Univ Ferrara, Inst Psychiat, Dept Biomed & Special Surg Sci, I-44100 Ferrara, Italy. RP Butow, P (reprint author), Univ Sydney, Sch Psychol, Level 6 North,Lifehouse C39Z, Sydney, NSW 2006, Australia. EM phyllis.butow@sydney.edu.au FU Intramural NIH HHS [Z99 CA999999] NR 40 TC 2 Z9 2 U1 10 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2016 VL 25 IS 2 BP 194 EP 202 DI 10.1002/pon.3902 PG 9 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DD5RH UT WOS:000369981400010 PM 26239424 ER PT J AU Stewart, RW Tuerk, PW Metzger, IW Davidson, TM Young, J AF Stewart, Regan W. Tuerk, Peter W. Metzger, Isha W. Davidson, Tatiana M. Young, John TI A Decision-Tree Approach to the Assessment of Posttraumatic Stress Disorder: Engineering Empirically Rigorous and Ecologically Valid Assessment Measures SO PSYCHOLOGICAL SERVICES LA English DT Article DE PTSD; assessment; screening; decision-tree analysis; veterans ID ADMINISTERED PTSD SCALE; MENTAL-HEALTH; TREATMENT SEEKING; VIETNAM VETERANS; ASSESSMENT TOOLS; PRIMARY-CARE; CLINICIAN; CLASSIFICATION; SAMPLE; ADOLESCENTS AB Structured diagnostic interviews are widely considered to be the optimal method of assessing symptoms of posttraumatic stress; however, few clinicians report using structured assessments to guide clinical practice. One commonly cited impediment to these assessment approaches is the amount of time required for test administration and interpretation. Empirically keyed methods to reduce the administration time of structured assessments may be a viable solution to increase the use of standardized and reliable diagnostic tools. Thus, the present research conducted an initial feasibility study using a sample of treatment-seeking military veterans (N = 1,517) to develop a truncated assessment protocol based on the Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS). Decision-tree analysis was utilized to identify a subset of predictor variables among the CAPS items that were most predictive of a diagnosis of PTSD. The algorithm-driven, atheoretical sequence of questions reduced the number of items administered by more than 75% and classified the validation sample at 92% accuracy. These results demonstrated the feasibility of developing a protocol to assess PTSD in a way that imposes little assessment burden while still providing a reliable categorization. C1 [Stewart, Regan W.; Tuerk, Peter W.; Metzger, Isha W.; Davidson, Tatiana M.; Young, John] Med Univ S Carolina, Dept Psychol & Behav Sci, 67 President St,2nd Floor,South Bldg,MSC 861, Charleston, SC 29425 USA. [Tuerk, Peter W.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Young, John] Univ Mississippi, Dept Psychol, University, MS 38677 USA. RP Stewart, RW (reprint author), Med Univ S Carolina, Dept Psychol & Behav Sci, 67 President St,2nd Floor,South Bldg,MSC 861, Charleston, SC 29425 USA. EM stewartr@musc.edu FU Career Development Award from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development [CDA-2] FX Peter W. Tuerk's contribution to this article was partially supported by a Career Development Award (CDA-2) from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development (principal investigator: Peter W. Tuerk). NR 70 TC 1 Z9 1 U1 3 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD FEB PY 2016 VL 13 IS 1 BP 1 EP 9 DI 10.1037/ser0000069 PG 9 WC Psychology, Clinical SC Psychology GA DD0FJ UT WOS:000369595500001 PM 26654473 ER PT J AU Keller, SM Tuerk, PW AF Keller, Stephanie M. Tuerk, Peter W. TI Evidence-Based Psychotherapy (EBP) Non-Initiation Among Veterans Offered an EBP for Posttraumatic Stress Disorder SO PSYCHOLOGICAL SERVICES LA English DT Article DE PTSD; treatment initiation; veterans; evidence-based psychotherapy ID PROLONGED EXPOSURE THERAPY; COGNITIVE PROCESSING THERAPY; MENTAL-HEALTH-SERVICES; TRAUMATIC BRAIN-INJURY; PTSD TREATMENT; AFGHANISTAN VETERANS; IRAQ; CARE; IMPLEMENTATION; ADHERENCE AB Current efforts to disseminate evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD) in Veterans Affairs Medical Centers (VAMCs) have made effective treatment options more available throughout the system. Yet many veterans identified as likely to benefit from such services choose not to utilize them. The evidence base retarding factors that contribute to treatment initiation among those offered EBPs is still in its early-stages. The present study investigated clinical presentation, patient demographics, and environment of care factors as potential predictors of EBP treatment initiation among veterans offered such care,. The sample consisted of 324 Veterans (62% Operation Enduring Freedom [OEF]/Operation Iraqi Freedom [OM; 77% male; age M = 42.95 SD = 12.57 years), who attended an intake evaluation at a VAMC outpatient PTSD Clinical Team, were diagnosed with PTSD, and offered a course of EBP. Overall, 720 of veterans (11 = 232) who were offered an FOP initiated such treatment, and 28% of veterans (n = 92) did not initiate treatment. Veterans who initiated treatment were significantly older. Treatment initiation did not significantly differ by ethnicity, gender, or baseline PTSD severity. Significantly more veterans referred from mental health clinics initiated treatment than did veterans referred from primary care. This study examined treatment initiation among veterans who were offered FOP for PTSD. Rates of initiation differed across subgroups of veterans. Clinically, this suggests the need to tailor outreach efforts to younger veterans, OEF/OLF veterans, and veterans referred from primary care, and potentially including programming and education aimed at primary care referrers, to increase help-seeking. C1 [Keller, Stephanie M.; Tuerk, Peter W.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. [Keller, Stephanie M.; Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. RP Keller, SM (reprint author), Ralph H Johnson VA Med Ctr, Menhil Hlth, 109 Bee St,116, Charleston, SC 29401 USA. EM smp28@case.edu FU CDA-2 award from the Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development [NCT01031979] FX Peter W. Tuerk's contribution to his research was supported in part by funding from a CDA-2 award from the Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development (principal investigator: Peter W. Tuerk; NCT01031979). NR 40 TC 0 Z9 0 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD FEB PY 2016 VL 13 IS 1 BP 42 EP 48 DI 10.1037/ser0000064 PG 7 WC Psychology, Clinical SC Psychology GA DD0FJ UT WOS:000369595500005 PM 26654474 ER PT J AU Di Leone, BAL Wang, JM Kressin, N Vogt, D AF Di Leone, Brooke A. L. Wang, Joyce M. Kressin, Nancy Vogt, Dawne TI Women's Veteran Identity and Utilization of VA Health Services SO PSYCHOLOGICAL SERVICES LA English DT Article DE veterans; identity; health services; veteran identity; mental health ID POSTTRAUMATIC-STRESS-DISORDER; GROUP IDENTIFICATION; PSYCHOMETRIC PROPERTIES; ADMINISTRATION CARE; SOCIAL IDENTITY; SELF-ESTEEM; DEPRESSION; DEPLOYMENT; INVENTORY; GENDER AB Women have participated in the United States military since its founding. However, until the mid-20th century, there had been limited recognition of women as official members of the military, and women remain a statistical minority within military and veteran populations. It is therefore important to better understand women's veteran identity (which we define here as one's self-concept as derived from their veteran status) and associated implications for service use and experiences in the Department of Veterans Affairs (VA) health care setting. The present research examined the centrality of, and positive regard for, women's veteran identity among 407 female veterans deployed in support of the recent wars in Iraq and Afghanistan. Data were collected via a mailed national survey. Positive regard for veteran identity, but not veteran identity centrality, was positively associated with participants' age and length of time spent in the military. Results also showed that the centrality of women's veteran identity was positively related to their choice to use VA for health care and their feelings of belonging within VA, and that veteran identity centrality and positive regard for veteran identity are differentially associated with participants' military experiences (e.g., combat exposure, deployment sexual harassment) and mental health symptomatology (e.g., depression). C1 [Di Leone, Brooke A. L.; Vogt, Dawne] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wang, Joyce M.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Kressin, Nancy] VA Boston Healthcare Syst, Hlth Serv Res & Dev Serv, Boston, MA USA. [Wang, Joyce M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kressin, Nancy] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Vogt, Dawne] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Wang, Joyce M.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Di Leone, BAL (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, 3900 Woodland Ave,Annex Bldg,CHERP Suite 202, Philadelphia, PA 19147 USA. EM brooke.dileone@va.gov FU Department of Veterans Affairs Health Sciences Research and Development Service [DHI 06-225-2]; Department of Veterans Affairs, Health Services Research & Development Service [RCS 02-066-1] FX This research was supported, in part, by a Department of Veterans Affairs Health Sciences Research and Development Service grant (DHI 06-225-2; Gender, Stigma, and Other Barriers to Veterans Health Administration (VITA) Use for Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) Veterans; PI: Dawne Vogt). Nancy Kressin is also supported in part by a Research Career Scientist award from the Department of Veterans Affairs, Health Services Research & Development Service (RCS 02-066-1). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 48 TC 2 Z9 2 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD FEB PY 2016 VL 13 IS 1 BP 60 EP 68 DI 10.1037/ser0000021 PG 9 WC Psychology, Clinical SC Psychology GA DD0FJ UT WOS:000369595500008 PM 25729892 ER PT J AU Johnson, L Shipherd, J Walton, HM AF Johnson, Laura Shipherd, Jillian Walton, Heather M. TI The Psychologist's Role in Transgender-Specific Care With US Veterans SO PSYCHOLOGICAL SERVICES LA English DT Article DE transgender; veteran; military; psychology; LOGT ID MINORITY VETERANS; MENTAL-HEALTH; PROVIDERS; STRESS AB Psychologists are integral to the care of transgender individuals. This article details the many roles for psychologists in transgender-specific care, including diagnosing and treating gender dysphoria; providing treatment for comorbid conditions; referring to medical services such as gender confirmation surgeries, voice modification, and cross-sex hormone therapies; serving as consultants within health care systems; and advocating for addressing harriers in systems in which transgender individuals live and work. Transgender veterans have unique experiences and vulnerabilities related to their military service that are detailed from a review of the literature, and we make the case that Veterans Health Administration (VITA) and community psychologists are well-positioned to provide care to transgender veterans (trans-vets). In this article, the authors describe the experiences that many trans-vets have faced, identify the importance of treatment for gender dysphoria (and draw the distinction between gender identity disorder and gender dysphoria) as well as psychologists' roles, and clarify which transgender-related services are available to eligible veterans though VHA per policy and how VHA providers have access to training to provide that care. In addition, we describe how veterans can connect to the VITA, even if they have (and want to continue working with) non-VITA psychologists or other community providers. C1 [Johnson, Laura] Edith Nourse Rogers Mem Vet Hosp, Psychol Serv, Bedford, MA USA. [Shipherd, Jillian] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Shipherd, Jillian] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Shipherd, Jillian] Boston Univ, Sch Med, Boston, MA 02118 USA. [Shipherd, Jillian] Vet Affairs Cent Off, Patient Care Serv, Washington, DC USA. [Walton, Heather M.] Vet Affairs Boston Healthcare Syst, Psychol Serv, Brockton, MA USA. [Walton, Heather M.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Johnson, L (reprint author), USAF, 60 MDOS SGOW, Fairfield, CA 94535 USA. EM laura.johnson9@va.gov FU Department of Veterans Affairs, Veterans Health Administration FX 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, U.S. Air Force, Department of Defense, or the U.S. government. This material is based on work supported by the Department of Veterans Affairs, Veterans Health Administration. NR 36 TC 6 Z9 6 U1 3 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD FEB PY 2016 VL 13 IS 1 BP 69 EP 76 DI 10.1037/ser0000030 PG 8 WC Psychology, Clinical SC Psychology GA DD0FJ UT WOS:000369595500010 PM 25961643 ER PT J AU Jahn, DR Bennett, ME Park, SG Gur, RE Horan, WP Kring, AM Blanchard, JJ AF Jahn, Danielle R. Bennett, Melanie E. Park, Stephanie G. Gur, Raquel E. Horan, William P. Kring, Ann M. Blanchard, Jack J. TI The interactive effects of negative symptoms and social role functioning on suicide ideation in individuals with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Social anhedonia; Social closeness; Belonging; Moderation; Protective factors ID PSYCHIATRIC RATING-SCALE; RISK-FACTORS; DEPRESSIVE SYMPTOMS; COMPLETED SUICIDE; DISORDERS; ANHEDONIA; LIFE; MOTIVATION; COMMUNITY; SPECTRUM AB Findings regarding the protective effect of social role functioning on suicide ideation in individuals with schizophrenia have been mixed. One reason for such inconsistencies in the literature may be that individuals with prominent negative symptoms of schizophrenia may not experience a desire for social closeness, and therefore social role functioning may not influence suicide risk in these individuals. The aim of this study was to examine the moderating effects of self-reported desire for social closeness and interviewer-rated negative symptoms on the relationship between social role functioning and suicide ideation. Our sample consisted of 162 individuals who had been diagnosed with schizophrenia-spectrum disorders; all participants completed self-report questionnaires and clinician-administered interviews, and moderation hypotheses were tested with a non parametric procedure. The results indicated that motivation and pleasure-related negative symptoms moderated the relationship between social role functioning and suicide ideation; self-reported desire for social closeness and negative symptoms related to expression did not have such a moderating effect. Specifically, better social role functioning was associated with less suicide ideation only in those individuals who had low motivation and pleasure-related negative symptoms; no significant relationship was observed between social role functioning and suicide ideation among those with elevated motivation and pleasure-related negative symptoms. These findings suggest that assessing for negative symptoms and social role functioning may inform suicide risk assessments in individuals with schizophrenia, and improving social role functioning may reduce suicide ideation among those with few motivation and pleasure-related negative symptoms. (c) 2015 Elsevier B.V. All rights reserved. C1 [Jahn, Danielle R.; Bennett, Melanie E.; Park, Stephanie G.] VA Maryland Hlth Care Syst, VA Capitol Hlth Care Network VISN 5, Mental Illness Res Educ & Clin Ctr, 10 N Greene St Annex Room 723A, Baltimore, MD 21201 USA. [Jahn, Danielle R.; Bennett, Melanie E.; Park, Stephanie G.] Univ Maryland, Sch Med, Dept Psychiat, 737 W Lombard St,Suite 551, Baltimore, MD 21201 USA. [Gur, Raquel E.] Univ Penn, Perelman Sch Med, Dept Psychiat, 10th Floor Gates Bldg, Philadelphia, PA 19104 USA. [Horan, William P.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Jane & Terry Semel Inst Neurosci & Human Behav, 760 Westwood Plaza, Los Angeles, CA 90095 USA. [Horan, William P.] VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 210,Mail Code 210A, Los Angeles, CA 90073 USA. [Kring, Ann M.] Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA. [Blanchard, Jack J.] Univ Maryland, Dept Psychol, 1147 Biol Psychol Bldg, College Pk, MD 20742 USA. RP Blanchard, JJ (reprint author), Univ Maryland, 1147 Biol Psychol Bldg, College Pk, MD 20742 USA. EM danielle.jahn@va.gov; mbennett@p.sych.umaryland.edu; stephanie.park3@va.gov; raquel@upenn.edu; horan@ucla.edu; kring@berkeley.edu; jblancha@umd.edu FU NIH [1R01MH082839]; Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs FX This work was supported by NIH grant (1R01MH082839) to Dr. Blanchard. Writing of this manuscript was supported by the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs (Dr. Jahn and Dr. Park's time). The funding sources had no role in study design or in the collection, analysis and interpretation of data, or in the writing of this report. NR 43 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2016 VL 170 IS 2-3 BP 271 EP 277 DI 10.1016/j.schres.2015.12.011 PG 7 WC Psychiatry SC Psychiatry GA DD0LS UT WOS:000369612100006 PM 26746862 ER PT J AU Manchikanti, L Kaye, AD Hirsch, JA AF Manchikanti, Laxmaiah Kaye, Alan David Hirsch, Joshua A. TI Short-term Improvements in Disability Mediate Patient Satisfaction After Epidural Corticosteroid Injections for Symptomatic Lumbar Spinal Stenosis SO SPINE LA English DT Letter ID RANDOMIZED-TRIAL C1 [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 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, Louisville, KY 40292 USA.; Manchikanti, L (reprint author), Pain Management Ctr Paducah, Paducah, KY USA. EM drlm@thepainmd.com NR 3 TC 0 Z9 0 U1 2 U2 2 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 FEB PY 2016 VL 41 IS 3 BP E183 EP E183 DI 10.1097/BRS.0000000000001357 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DD5VS UT WOS:000369993400001 ER PT J AU Manchikanti, L Kaye, AD Hirsch, JA AF Manchikanti, Laxmaiah Kaye, Alan David Hirsch, Joshua A. TI Re: Suri, P. et al. Short-term Improvements in Disability Mediate Patient Satisfaction After Epidural Corticosteroid Injections for Symptomatic Lumbar Spinal Stenosis. Spine (Phila Pa 1976) 2015 May 22. SO SPINE LA English DT Letter ID RANDOMIZED-TRIAL C1 [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 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, Louisville, KY 40292 USA. EM drlm@thepainmd.com 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 FEB PY 2016 VL 41 IS 3 BP E183 EP E183 DI 10.1097/BRS.0000000000001357 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DD5VR UT WOS:000369993300012 ER PT J AU Suri, P Pashova, H Heagerty, PJ Jarvik, JG Turner, JA Bauer, Z Annaswamy, M Nedeljkovic, SS Wasan, AD Friedly, JL AF Suri, Pradeep Pashova, Hristina Heagerty, Patrick J. Jarvik, Jeffrey G. Turner, Judith A. Bauer, Zoya Annaswamy, M. Nedeljkovic, Srdjan S. Wasan, Ajay D. Friedly, Janna L. TI Short-term Improvements in Disability Mediate Patient Satisfaction After Epidural Corticosteroid Injections for Symptomatic Lumbar Spinal Stenosis Reply SO SPINE LA English DT Letter ID TRIAL C1 [Suri, Pradeep] VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Dallas VA Med Ctr, Dallas, TX USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Suri, P (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM pradeep.suri@va.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD FEB PY 2016 VL 41 IS 3 BP E183 EP E184 DI 10.1097/BRS.0000000000001142 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DD5VS UT WOS:000369993400002 ER PT J AU Suri, P Pashova, H Heagerty, PJ Jarvik, JG Turner, JA Bauer, Z Annaswamy, TM Nedeljkovic, SS Wasan, AD Friedly, JL AF Suri, Pradeep Pashova, Hristina Heagerty, Patrick J. Jarvik, Jeffrey G. Turner, Judith A. Bauer, Zoya Annaswamy, Thiru M. Nedeljkovic, Srdjan S. Wasan, Ajay D. Friedly, Janna L. TI Re: Suri, P. et al. Short-term Improvements in Disability Mediate Patient Satisfaction After Epidural Corticosteroid Injections for Symptomatic Lumbar Spinal Stenosis. Spine (Phila Pa 1976) 2015 May 22. Reply SO SPINE LA English DT Letter ID TRIAL C1 [Suri, Pradeep] VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Dallas VA Med Ctr, Dallas, TX USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Suri, P (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM pradeep.suri@va.gov NR 4 TC 0 Z9 0 U1 2 U2 2 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 FEB PY 2016 VL 41 IS 3 BP E183 EP E184 DI 10.1097/BRS.0000000000001142 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DD5VR UT WOS:000369993300013 ER PT J AU Monteith, LL Menefee, DS Forster, JE Bahraini, NH AF Monteith, Lindsey L. Menefee, Deleene S. Forster, Jeri E. Bahraini, Nazanin H. TI A Closer Examination of Sexual Trauma During Deployment: Not all Sexual Traumas are Associated with Suicidal Ideation SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; GENDER-DIFFERENCES; MENTAL-HEALTH; MILITARY PERSONNEL; OEF/OIF VETERANS; FOLLOW-UP; ASSAULT; HARASSMENT; EXPERIENCES; AFGHANISTAN AB Military personnel can be exposed to a wide range of sexual traumawhile deployed, including sexual harassment and sexual assault. We examined whether different types of sexual trauma during deployment associated with recent suicidal ideation among previously deployed OEF/OIF/OND veterans admitted to trauma-focused treatment (n=199). More severe forms of sexual trauma (e.g., sexual assault) were significantly and positively associated with suicidal ideation. In contrast, sexual trauma involving verbal remarks (e.g., sexual harassment) was not associated with suicidal ideation. Our findings suggest that sexual harassment and sexual assault during deployment may be differentially associated with suicidal ideation. C1 [Monteith, Lindsey L.; Forster, Jeri E.; Bahraini, Nazanin H.] VISN 19 MIRECC, Denver Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO USA. [Monteith, Lindsey L.; Bahraini, Nazanin H.] Univ Colorado, Dept Psychiat, Anschutz Med Campus, Aurora, CO USA. [Menefee, Deleene S.] VISN 16 MIRECC, Michael F DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Menefee, Deleene S.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Forster, Jeri E.] Colorado Sch Publ Hlth, Aurora, CO USA. RP Monteith, LL (reprint author), VISN 19 MIRECC, Denver Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO USA. EM lindsey.monteith@va.gov FU Denver Veterans Affairs Medical Center; MEDVAMC; VISN 19 MIRECC in Denver, Colorado; VISN 16 MIRECC in Houston, Texas FX This material is the result of work supported with resources and the use of facilities at the Denver Veterans Affairs Medical Center and VISN 19 MIRECC in Denver, Colorado, and the MEDVAMC and VISN 16 MIRECC in Houston, Texas. The views expressed are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the U.S. Government. 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 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD FEB PY 2016 VL 46 IS 1 BP 46 EP 54 DI 10.1111/sltb.12171 PG 9 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DD7WS UT WOS:000370136200005 PM 26096625 ER PT J AU Peroni, M Golland, P Sharp, GC Baroni, G AF Peroni, M. Golland, P. Sharp, G. C. Baroni, G. TI Stopping Criteria for Log-Domain Diffeomorphic Demons Registration: An Experimental Survey for Radiotherapy Application SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE Optimization; Deformable registration; Demons; Stopping criteria ID DEFORMABLE IMAGE REGISTRATION; HEAD; GPU AB A crucial issue in deformable image registration is achieving a robust registration algorithm at a reasonable computational cost. Given the iterative nature of the optimization procedure an algorithm must automatically detect convergence, and stop the iterative process when most appropriate. This paper ranks the performances of three stopping criteria and six stopping value computation strategies for a Log-Domain Demons Deformable registration method simulating both a coarse and a fine registration. The analyzed stopping criteria are: (a) velocity field update magnitude, (b) mean squared error, and (c) harmonic energy. Each stoping condition is formualted so that the user defines a threshold , which quantifies the residual error that is acceptable for the particular problem and calculation strategy. In this work, we did not aim at assigning a value to e, but to give insights in how to evaluate and to set the threshold on a given exit strategy in a very popular registration scheme. Experi-ments on phantom and patient data demonstrate that comparing the optimization metric minimum over the most recent three iterations with the minimum over the fourth to sixth most recent iterations can be an appropriate algorithm stopping strategy. The harmonic energy was found to provide best trade-off between robustness and speed of convergence for the analyzed registration method at coarse registration, but was outperformed by mean squared error when all the original pixel information is used. This suggests the need of developing mathematically sound new convergence criteria in which both image and vector field information could be used to detect the actual convergence, which could be especially useful when considering multi-resolution registrations. Further work should be also dedicated to study same strategies performances in other deformable registration methods and body districts. C1 [Peroni, M.; Baroni, G.] Politecn Milan, Dipartimento Elettron Informaz & Bioingn, I-20133 Milan, Italy. [Golland, P.] MIT, Comp Sci & Artificial Intelligence Lab, Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Sharp, G. C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Sharp, G. C.] Harvard Univ, Sch Med, Boston, MA USA. [Baroni, G.] Ctr Nazl Adroterapia Oncol, Bioengn Unit, Pavia, Italy. RP Peroni, M (reprint author), Politecn Milan, Dipartimento Elettron Informaz & Bioingn, I-20133 Milan, Italy. EM marta.peroni@psi.ch FU Rocca Fundation; National Alliance for Medical Image Computing (NAMIC), NIH [2-U54EB005149-06] FX This work was supported in part by the Rocca Fundation and the National Alliance for Medical Image Computing (NAMIC), NIH Grant 2-U54EB005149-06. The authors would like to thank the Advanced Radiotherapy Center, European Institute of Oncology, Milan, Italy for providing dataset used in this project. NR 18 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-0346 EI 1533-0338 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD FEB PY 2016 VL 15 IS 1 BP 77 EP 90 DI 10.7785/tcrtexpress.2013.600269 PG 14 WC Oncology SC Oncology GA DD5OS UT WOS:000369974200010 PM 24000996 ER PT J AU Pomerantseva, I Bichara, DA Tseng, A Cronce, MJ Cervantes, TM Kimura, AM Neville, CM Roscioli, N Vacanti, JP Randolph, MA Sundback, CA AF Pomerantseva, Irina Bichara, David A. Tseng, Alan Cronce, Michael J. Cervantes, Thomas M. Kimura, Anya M. Neville, Craig M. Roscioli, Nick Vacanti, Joseph P. Randolph, Mark A. Sundback, Cathryn A. TI Ear-Shaped Stable Auricular Cartilage Engineered from Extensively Expanded Chondrocytes in an Immunocompetent Experimental Animal Model SO TISSUE ENGINEERING PART A LA English DT Article ID IN-VITRO; PASSAGED CHONDROCYTES; TISSUE FORMATION; ACID SCAFFOLDS; RECONSTRUCTION; FGF-2; VIVO; NEOCARTILAGE; INHIBITION; MATURATION AB Advancement of engineered ear in clinical practice is limited by several challenges. The complex, largely unsupported, three-dimensional auricular neocartilage structure is difficult to maintain. Neocartilage formation is challenging in an immunocompetent host due to active inflammatory and immunological responses. The large number of autologous chondrogenic cells required for engineering an adult human-sized ear presents an additional challenge because primary chondrocytes rapidly dedifferentiate during in vitro culture. The objective of this study was to engineer a stable, human ear-shaped cartilage in an immunocompetent animal model using expanded chondrocytes. The impact of basic fibroblast growth factor (bFGF) supplementation on achieving clinically relevant expansion of primary sheep chondrocytes by in vitro culture was determined. Chondrocytes expanded in standard medium were either combined with cryopreserved, primary passage 0 chondrocytes at the time of scaffold seeding or used alone as control. Disk and human ear-shaped scaffolds were made from porous collagen; ear scaffolds had an embedded, supporting titanium wire framework. Autologous chondrocyte-seeded scaffolds were implanted subcutaneously in sheep after 2 weeks of in vitro incubation. The quality of the resulting neocartilage and its stability and retention of the original ear size and shape were evaluated at 6, 12, and 20 weeks postimplantation. Neocartilage produced from chondrocytes that were expanded in the presence of bFGF was superior, and its quality improved with increased implantation time. In addition to characteristic morphological cartilage features, its glycosaminoglycan content was high and marked elastin fiber formation was present. The overall shape of engineered ears was preserved at 20 weeks postimplantation, and the dimensional changes did not exceed 10%. The wire frame within the engineered ear was able to withstand mechanical forces during wound healing and neocartilage maturation and prevented shrinkage and distortion. This is the first demonstration of a stable, ear-shaped elastic cartilage engineered from auricular chondrocytes that underwent clinical-scale expansion in an immunocompetent animal over an extended period of time. C1 [Pomerantseva, Irina; Tseng, Alan; Cronce, Michael J.; Cervantes, Thomas M.; Kimura, Anya M.; Neville, Craig M.; Vacanti, Joseph P.; Sundback, Cathryn A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Pomerantseva, Irina; Bichara, David A.; Neville, Craig M.; Vacanti, Joseph P.; Randolph, Mark A.; Sundback, Cathryn A.] Harvard Univ, Sch Med, Boston, MA USA. [Bichara, David A.; Randolph, Mark A.] Massachusetts Gen Hosp, Plast Surg Res Lab, Boston, MA 02114 USA. [Roscioli, Nick] DSM Biomed Corp, Exton, PA USA. RP Sundback, CA (reprint author), Massachusetts Gen Hosp, CPZN 4809,185 Cambridge St, Boston, MA 02114 USA. EM csundback@partners.org FU U.S. Army Medical Research and Materiel Command [W81XWH-12-1-0334]; Armed Forces Institute of Regenerative Medicine [W81XWH-08-2-0034] FX This research was sponsored in part by the U.S. Army Medical Research and Materiel Command award No. W81XWH-12-1-0334 and by the Armed Forces Institute of Regenerative Medicine award No. W81XWH-08-2-0034. The content of this article does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. The fibrous collagen scaffolds were generously provided by the DSM Biomedical Corp. The authors would like to thank Drs. T. Hadlock and M. Cheney for their valuable input on ear scaffold design and M. Johnson and J. Beagle for excellent animal care assistance. NR 45 TC 4 Z9 4 U1 2 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD FEB 1 PY 2016 VL 22 IS 3-4 BP 197 EP 207 DI 10.1089/ten.tea.2015.0173 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA DD5TS UT WOS:000369987900002 PM 26529401 ER PT J AU Saxena, V Kim, M Keah, NM Neuwirth, AL Stoeckl, BD Bickard, K Restle, DJ Salowe, R Wang, MY Steinberg, DR Mauck, RL AF Saxena, Vishal Kim, Minwook Keah, Niobra M. Neuwirth, Alexander L. Stoeckl, Brendan D. Bickard, Kevin Restle, David J. Salowe, Rebecca Wang, Margaret Ye Steinberg, David R. Mauck, Robert L. TI Anatomic Mesenchymal Stem Cell-Based Engineered Cartilage Constructs for Biologic Total Joint Replacement SO TISSUE ENGINEERING PART A LA English DT Article ID HYALURONIC-ACID HYDROGELS; ARTICULAR-CARTILAGE; POROUS TANTALUM; NUTRIENT CHANNELS; TISSUE; KNEE; REPAIR; BONE; REGENERATION; GROWTH AB Cartilage has a poor healing response, and few viable options exist for repair of extensive damage. Hyaluronic acid (HA) hydrogels seeded with mesenchymal stem cells (MSCs) polymerized through UV crosslinking can generate functional tissue, but this crosslinking is not compatible with indirect rapid prototyping utilizing opaque anatomic molds. Methacrylate-modified polymers can also be chemically crosslinked in a cytocompatible manner using ammonium persulfate (APS) and N,N,N,N-tetramethylethylenediamine (TEMED). The objectives of this study were to (1) compare APS/TEMED crosslinking with UV crosslinking in terms of functional maturation of MSC-seeded HA hydrogels; (2) generate an anatomic mold of a complex joint surface through rapid prototyping; and (3) grow anatomic MSC-seeded HA hydrogel constructs using this alternative crosslinking method. Juvenile bovine MSCs were suspended in methacrylated HA (MeHA) and crosslinked either through UV polymerization or chemically with APS/TEMED to generate cylindrical constructs. Minipig porcine femoral heads were imaged using microCT, and anatomic negative molds were generated by three-dimensional printing using fused deposition modeling. Molded HA constructs were produced using the APS/TEMED method. All constructs were cultured for up to 12 weeks in a chemically defined medium supplemented with TGF-3 and characterized by mechanical testing, biochemical assays, and histologic analysis. Both UV- and APS/TEMED-polymerized constructs showed increasing mechanical properties and robust proteoglycan and collagen deposition over time. At 12 weeks, APS/TEMED-polymerized constructs had higher equilibrium and dynamic moduli than UV-polymerized constructs, with no differences in proteoglycan or collagen content. Molded HA constructs retained their hemispherical shape in culture and demonstrated increasing mechanical properties and proteoglycan and collagen deposition, especially at the edges compared to the center of these larger constructs. Immunohistochemistry showed abundant collagen type II staining and little collagen type I staining. APS/TEMED crosslinking can be used to produce MSC-seeded HA-based neocartilage and can be used in combination with rapid prototyping techniques to generate anatomic MSC-seeded HA constructs for use in filling large and anatomically complex chondral defects or for biologic joint replacement. C1 [Saxena, Vishal; Kim, Minwook; Keah, Niobra M.; Neuwirth, Alexander L.; Stoeckl, Brendan D.; Bickard, Kevin; Restle, David J.; Salowe, Rebecca; Wang, Margaret Ye; Steinberg, David R.; Mauck, Robert L.] Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Stemmler Hall 36th St & Hamilton Walk, Philadelphia, PA 19104 USA. [Saxena, Vishal; Kim, Minwook; Keah, Niobra M.; Neuwirth, Alexander L.; Stoeckl, Brendan D.; Steinberg, David R.; Mauck, Robert L.] Philadelphia Vet Affairs Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA USA. [Kim, Minwook; Bickard, Kevin; Restle, David J.; Salowe, Rebecca; Wang, Margaret Ye; Mauck, Robert L.] Univ Penn, Dept Bioengn, Stemmler Hall 36th St & Hamilton Walk, Philadelphia, PA 19104 USA. RP Mauck, RL (reprint author), Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Stemmler Hall 36th St & Hamilton Walk, Philadelphia, PA 19104 USA.; Mauck, RL (reprint author), Philadelphia Vet Affairs Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA USA.; Mauck, RL (reprint author), Univ Penn, Dept Bioengn, Stemmler Hall 36th St & Hamilton Walk, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu FU National Institutes of Health [R01 EB008722]; Department of Veterans Affairs [I01 RX000700]; Penn Center for Musculoskeletal Disorders [P30 AR050950] FX This work was funded by the National Institutes of Health (R01 EB008722), the Department of Veterans Affairs (I01 RX000700), and the Penn Center for Musculoskeletal Disorders (P30 AR050950). NR 55 TC 1 Z9 1 U1 6 U2 14 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD FEB 1 PY 2016 VL 22 IS 3-4 BP 386 EP 395 DI 10.1089/ten.tea.2015.0384 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA DD5TS UT WOS:000369987900020 PM 26871863 ER PT J AU Karel, MJ Sakai, EY Molinari, V Moye, J Carpenter, B AF Karel, Michele J. Sakai, Erin Y. Molinari, Victor Moye, Jennifer Carpenter, Brian TI Training for Geropsychology Supervision and Practice: Perspectives of Geropsychology Program Graduates SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE geropsychology; supervision; training; competencies; older adults ID PROFESSIONAL GEROPSYCHOLOGY; COMPETENCE; PSYCHOLOGY; MODEL; BENCHMARKS; WORKFORCE AB Addressing the geropsychology workforce shortage requires ongoing training of psychologists to develop geropsychology competencies, as well as expanding the number of geropsychology supervisors to train them. This study surveyed graduates of geropsychology doctoral and postdoctoral training programs regarding their current geropsychology practice and supervision activities and perceptions of their own training preparation for these activities. One hundred psychologists (87 who had completed all formal training and 13 current postdoctoral fellows) responded to an online survey. Of those who had completed geropsychology training, 82% reported currently engaging in clinical care, and 55 reported providing supervision; more than half of clinical and supervision activities focused on older adults. Participants repotted generally strong quality of training to prepare them for providing geropsychology services; areas of more uneven preparation included family and group interventions and select consultation activities. Participants reported quite variable preparation for general supervision practice, and desire for more training and practice in supervisory roles. Geropsychology training programs may use feedback from graduates for ongoing program development, and professional geropsychology may wish to consider forums for enhancing geropsychology supervision skills. C1 [Karel, Michele J.] Dept Vet Affairs, Mental Hlth Serv, Cent Off, Washington, DC USA. [Sakai, Erin Y.; Carpenter, Brian] Washington Univ, St Louis, MO 63130 USA. [Molinari, Victor] Univ S Florida, Sch Aging Studies, Tampa, FL 33620 USA. [Moye, Jennifer] VA Boston Healthcare Syst, Geriatr Mental Hlth, Boston, MA USA. [Moye, Jennifer] Harvard Univ, Sch Med, Psychol, Cambridge, MA 02138 USA. RP Karel, MJ (reprint author), Dept Vet Affairs, Cent Off, Mental Hlth Serv 10P4M, 1575 1 St NW, Washington, DC 20420 USA. EM michele.karel@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Council of Professional Geropsychology Training Programs; VA Boston Healthcare System FX THIS RESEARCH WAS SUPPORTED in part by a grant from the Council of Professional Geropsychology Training Programs and from the VA Boston Healthcare System. This material is the result of work supported with the resources and the use of facilities at the VA Boston Healthcare System. The following geropsychologists reviewed an initial draft of the survey and provided invaluable feedback: Barry Edelstein, Amy Fiske, Greg Hinrichsen, Erlene Rosowsky, and Susan Whitbourne. The authors also wish to acknowledge the contributions of the many directors of clinical training who assisted with survey distribution and survey participants who generously shared then time and perspectives on training. NR 32 TC 0 Z9 0 U1 0 U2 1 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 EI 1931-3926 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD FEB PY 2016 VL 10 IS 1 BP 37 EP 44 DI 10.1037/tep0000101 PG 8 WC Psychology, Educational SC Psychology GA DD0FU UT WOS:000369596600006 PM 27594967 ER PT J AU Nagasaka, Y Wasner, G Sharma, B Fleischmann, K AF Nagasaka, Yasuko Wasner, Gunnar Sharma, Balram Fleischmann, Katharine TI Harlequin Syndrome After Thoracic Paravertebral Block SO A & A CASE REPORTS LA English DT Article ID COEXISTING HARLEQUIN; CAROTID-ARTERY; AUTONOMIC DEFICIT; HORNER-SYNDROMES; COLOR-CHANGE; DISSECTION; FACE; ANESTHESIA; NEURONS; INFANT AB Harlequin syndrome is characterized by the sudden onset of unilateral facial flushing and sweating, often preceded by exercise, excessive heat, or, rarely, regional anesthesia. Although the exact mechanism remains unclear, it is often referred to as transient or permanent interruption of the sympathetic nervous system. We present a case of Harlequin syndrome without Horner syndrome in a patient with unilateral right-sided facial flushing that started shortly after a left-sided thoracic paravertebral nerve block for a mastectomy. We discuss the interruption of the sympathetic and parasympathetic nervous system and the levels of spinal nerve block associated with a thoracic paravertebral nerve block. C1 [Nagasaka, Yasuko; Fleischmann, Katharine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Wasner, Gunnar] Univ Kiel, Neurol Outpatient Ctr, Kiel, Germany. [Sharma, Balram] Lahey Hosp & Med Ctr, Anesthesiol, Burlington, MA USA. RP Fleischmann, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM Fleischmann.Katharine@mgh.harvard.edu NR 40 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 2325-7237 J9 A A CASE REP JI A A Case Rep. PD FEB 1 PY 2016 VL 6 IS 3 BP 48 EP 51 DI 10.1213/XAA.0000000000000231 PG 4 WC Anesthesiology SC Anesthesiology GA DD0FG UT WOS:000369595200003 PM 26513674 ER PT J AU Stanford, FC Kyle, TK AF Stanford, Fatima Cody Kyle, Theodore K. TI Obesity Education Beyond Nutrition Education: Thinking Farther Outside the Box SO ACADEMIC MEDICINE LA English DT Letter C1 [Stanford, Fatima Cody] Massachusetts Gen Hosp, Weight Ctr, Dept Pediat, Dept Med,Div Gastroenterol,Med & Pediat, Boston, MA 02114 USA. [Stanford, Fatima Cody] Massachusetts Gen Hosp, Weight Ctr, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Stanford, Fatima Cody] Harvard Univ, Sch Med, Med & Pediat, Boston, MA USA. [Kyle, Theodore K.] ConscienHealth, Pittsburgh, PA USA. [Kyle, Theodore K.] Obes Act Coalit, Tampa, FL USA. RP Stanford, FC (reprint author), Massachusetts Gen Hosp, Weight Ctr, Dept Pediat, Dept Med,Div Gastroenterol,Med & Pediat, Boston, MA 02114 USA.; Stanford, FC (reprint author), Massachusetts Gen Hosp, Weight Ctr, Mongan Inst Hlth Policy, Boston, MA 02114 USA.; Stanford, FC (reprint author), Harvard Univ, Sch Med, Med & Pediat, Boston, MA USA. EM fstanford@mgh.harvard.edu OI Stanford, Fatima/0000-0003-4616-533X NR 5 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD FEB PY 2016 VL 91 IS 2 BP 164 EP 164 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DC5YP UT WOS:000369297000012 PM 26813650 ER PT J AU Goroll, AH AF Goroll, Allan H. TI Recruiting Quarterbacks: Strategies for Revitalizing Training in Primary Care Internal Medicine SO ACADEMIC MEDICINE LA English DT Editorial Material AB Current U.S. primary care workforce shortages and trainees' declining interest in primary care residency training, especially regarding primary care internal medicine, have many parallels with circumstances in the early 1970s, when modern adult primary care first emerged. Rediscovery of the lessons learned and the solutions developed at that time and applying them to the current situation have the potential to help engage a new generation of young physicians in the primary care mission. The author compares the internal medicine residency primary care track at the University of New Mexico, described by Brislen and colleagues in this issue, with the nation's first three-year primary care internal medicine residency track introduced at Massachusetts General Hospital in 1973. Strategies for addressing the challenges of primary care practice and improving learner attitudes toward the field are discussed. The author suggests that primary care physicians should be likened to quarterbacks rather than gatekeepers or providers to underscore the intensity of training, level of responsibility, degree of professionalism, and amount of compensation required for this profession. The advent of multidisciplinary team practice, modern health information technology, and fundamental payment reform promises to dramatically alter the picture of primary care, restoring its standing as one of the best job descriptions in medicine. C1 [Goroll, Allan H.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Goroll, Allan H.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Goroll, AH (reprint author), Massachusetts Gen Hosp, 15 Parkman St,Suite 645, Boston, MA 02114 USA. EM ahgoroll@partners.org 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 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD FEB PY 2016 VL 91 IS 2 BP 168 EP 170 DI 10.1097/ACM.0000000000000891 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DC5YP UT WOS:000369297000014 PM 26397701 ER PT J AU Calaman, S Hepps, JH Bismilla, Z Carraccio, C Englander, R Feraco, A Landrigan, CP Lopreiato, JO Sectish, TC Starmer, AJ Yu, CE Spector, ND West, DC AF Calaman, Sharon Hepps, Jennifer H. Bismilla, Zia Carraccio, Carol Englander, Robert Feraco, Angela Landrigan, Christopher P. Lopreiato, Joseph O. Sectish, Theodore C. Starmer, Amy J. Yu, Clifton E. Spector, Nancy D. West, Daniel C. CA I-Pass Study Educ Executive Comm TI The Creation of Standard-Setting Videos to Support Faculty Observations of Learner Performance and Entrustment Decisions SO ACADEMIC MEDICINE LA English DT Article ID CLINICAL SKILLS; TRIGGER FILMS; PROFESSIONAL ACTIVITIES; COMPETENCE; MODEL; ASSESSMENTS; EDUCATION; RATINGS; STUDENT AB Entrustable professional activities (EPAs) provide a framework to standardize medical education outcomes and advance competency-based assessment. Direct observation of performance plays a central role in entrustment decisions; however, data obtained from these observations are often insufficient to draw valid high-stakes conclusions. One approach to enhancing the reliability and validity of these assessments is to create videos that establish performance standards to train faculty observers. Little is known about how to create videos that can serve as standards for assessment of EPAs. The authors report their experience developing videos that represent five levels of performance for an EPA for patient handoffs. The authors describe a process that begins with mapping the EPA to the critical competencies needed to make an entrustment decision. Each competency is then defined by five milestones (behavioral descriptors of performance at five advancing levels). Integration of the milestones at each level across competencies enabled the creation of clinical vignettes that were converted into video scripts and ultimately videos. Each video represented a performance standard from novice to expert. The process included multiple assessments by experts to guide iterative improvements, provide evidence of content validity, and ensure that the authors successfully translated behavioral descriptions and vignettes into videos that represented the intended performance level for a learner. The steps outlined are generalizable to other EPAs, serving as a guide for others to develop videos to train faculty. This process provides the level of content validity evidence necessary to support using videos as standards for high-stakes entrustment decisions. C1 [Calaman, Sharon; Spector, Nancy D.] St Christophers Hosp Children, 160 E Erie Ave, Philadelphia, PA 19130 USA. [Calaman, Sharon] Drexel Univ, Coll Med, Dept Pediat, Philadelphia, PA 19104 USA. [Hepps, Jennifer H.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [Hepps, Jennifer H.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Bismilla, Zia] Univ Toronto, Dept Pediat, Toronto, ON, Canada. [Bismilla, Zia] Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. [Carraccio, Carol] Amer Board Pediat Inc, Competency Based Assessment, Chapel Hill, NC USA. [Englander, Robert] Assoc Amer Med Coll, Competency Based Learning & Assessment, Washington, DC USA. [Feraco, Angela] Harvard Univ, Sch Med, Dana Farber, Pediat Hematol Oncol, Boston, MA USA. [Feraco, Angela] Harvard Univ, Sch Med, Boston Childrens Hosp, Canc & Blood Disorders Ctr, Boston, MA USA. [Landrigan, Christopher P.] Harvard Univ, Sch Med, Dept Med & Pediat, Boston, MA USA. [Landrigan, Christopher P.; Sectish, Theodore C.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Landrigan, Christopher P.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Lopreiato, Joseph O.; Yu, Clifton E.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [Lopreiato, Joseph O.; Yu, Clifton E.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Sectish, Theodore C.; Starmer, Amy J.] Harvard Univ, Sch Med, Pediat, Boston, MA USA. [Starmer, Amy J.] Boston Childrens Hosp, Boston, MA USA. [Starmer, Amy J.] Oregon Hlth & Sci Univ, Dept Pediat, 3181 Sw Sam Jackson Pk Rd, Portland, OR 97201 USA. [Starmer, Amy J.] OHSU Doernbecher Childrens Hosp, Portland, OR USA. [Spector, Nancy D.] Drexel Univ, Coll Med, Dept Pediat, Pediat, Philadelphia, PA 19104 USA. [West, Daniel C.] Univ Calif San Francisco, Sch Med, Dept Pediat, Pediat, San Francisco, CA 94143 USA. [West, Daniel C.] UCSF Benioff Childrens Hosp, San Francisco, CA USA. RP Calaman, S (reprint author), St Christophers Hosp Children, 160 E Erie Ave, Philadelphia, PA 19130 USA. EM Sharon.calaman@drexelmed.edu FU U.S. Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation [1R18AE000029-01]; Children's Hospital Association; Academic Pediatric Association; American Academy of Pediatrics; Society of Hospital Medicine; Oregon Comparative Effectiveness Research K12 Program (Agency for Healthcare Research and Quality) [1K12HS019456-01]; Medical Research Foundation of Oregon; Physician Services Incorporated Foundation (of Ontario, Canada); Pfizer; American Board of Pediatrics Foundation FX The I-PASS Study is primarily supported by the U.S. Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation (1R18AE000029-01). The study was developed with input from the Initiative for Innovation in Pediatric Education and the Pediatric Research in Inpatient Settings Network (supported by the Children's Hospital Association, the Academic Pediatric Association, the American Academy of Pediatrics, and the Society of Hospital Medicine). A.J.S. was supported by the Oregon Comparative Effectiveness Research K12 Program (Agency for Healthcare Research and Quality, 1K12HS019456-01). Additional funding for the I-PASS Study is provided by the Medical Research Foundation of Oregon, Physician Services Incorporated Foundation (of Ontario, Canada), and Pfizer (unrestricted medical education grant). Computer modules used in the I-PASS curriculum were developed by Concurrent Technologies Corporation. This project was also supported by a contribution from the American Board of Pediatrics Foundation. NR 30 TC 3 Z9 3 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD FEB PY 2016 VL 91 IS 2 BP 204 EP 209 DI 10.1097/ACM.0000000000000853 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DC5YP UT WOS:000369297000021 PM 26266461 ER PT J AU Fitzsimons, MG Brookman, JC Arnholz, SH Baker, K AF Fitzsimons, Michael G. Brookman, Jason C. Arnholz, Sarah H. Baker, Keith TI Attention-Deficit/Hyperactivity Disorder and Successful Completion of Anesthesia Residency: A Case Report SO ACADEMIC MEDICINE LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; MEDICATION-TREATED ADULTS; LEARNING-DISABILITIES; STUDENTS; SYMPTOMS; SCHOOLS; ADHD AB Cognitive and physical disabilities among anesthesia residents are not well studied. Cognitive disabilities may often go undiagnosed among trainees, and these trainees may struggle during their graduate medical education. Attention-deficit/hyperactivity disorder (ADHD) is an executive function disorder that may manifest as lack of vigilance, an inability to adapt to the rapid changes associated with anesthesia cases, distractibility, an inability to prioritize activities, and even periods of hyperfocusing, among other signs. Programs are encouraged to work closely with residents with such disabilities to develop an educational plan that includes accommodations for their unique learning practices while maintaining the critical aspects of the program. The authors present the management of a case of an anesthesia resident with a diagnosis of ADHD, the perspectives of the trainee, program director, clinical competency director, and the office of general counsel. This article also provides follow-up in the five years since completion of residency. C1 [Fitzsimons, Michael G.; Baker, Keith] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. [Fitzsimons, Michael G.; Baker, Keith] Harvard Univ, Sch Med, Boston, MA USA. [Brookman, Jason C.] Johns Hopkins Med, Dept Anesthesiol & Crit Care Med, Anesthesiol, Baltimore, MD USA. [Arnholz, Sarah H.] Partners Healthcare Syst, Off Gen Counsel, Boston, MA USA. RP Fitzsimons, MG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mfitzsimons@partners.org NR 15 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD FEB PY 2016 VL 91 IS 2 BP 210 EP 214 DI 10.1097/ACM.0000000000000854 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DC5YP UT WOS:000369297000022 PM 26244258 ER PT J AU Montine, TJ Monsell, SE Beach, TG Bigio, EH Bu, YQ Cairns, NJ Frosch, M Henriksen, J Kofler, J Kukull, WA Lee, EB Nelson, PT Schantz, AM Schneider, JA Sonnen, JA Trojanowski, JQ Vinters, HV Zhou, XH Hyman, BT AF Montine, Thomas J. Monsell, Sarah E. Beach, Thomas G. Bigio, Eileen H. Bu, Yunqi Cairns, Nigel J. Frosch, Matthew Henriksen, Jonathan Kofler, Julia Kukull, Walter A. Lee, Edward B. Nelson, Peter T. Schantz, Aimee M. Schneider, Julie A. Sonnen, Joshua A. Trojanowski, John Q. Vinters, Harry V. Zhou, Xiao-Hua Hyman, Bradley T. TI Multisite assessment of NIA-AA guidelines for the neuropathologic evaluation of Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Neuropathology; Methods; Whole-slide imaging; Multisite ID BRAINNET EUROPE CONSORTIUM; ASSOCIATION GUIDELINES; NATIONAL INSTITUTE; AGREEMENT; PATHOLOGY AB Introduction: Neuropathologic assessment is the current "gold standard" for evaluating the Alzheimer's disease (AD), but there is no consensus on the methods used. Methods: Fifteen unstained slides (8 brain regions) from each of the 14 cases were prepared and distributed to 10 different National Institute on Aging AD Centers for application of usual staining and evaluation following recently revised guidelines for AD neuropathologic change. Results: Current practice used in the AD Centers Program achieved robustly excellent agreement for the severity score for AD neuropathologic change (average weighted kappa = .88, 95% confidence interval: 0.77-0.95) and good-to-excellent agreement for the three supporting scores. Some improvement was observed with consensus evaluation but not with central staining of slides. Evaluation of glass slides and digitally prepared whole-slide images was comparable. Discussion: AD neuropathologic evaluation as performed across AD Centers yields data that have high agreement with potential modifications for modest improvements. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Montine, Thomas J.; Henriksen, Jonathan; Schantz, Aimee M.; Sonnen, Joshua A.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Monsell, Sarah E.; Bu, Yunqi; Kukull, Walter A.; Zhou, Xiao-Hua] Univ Washington, Natl Alzheimer Coordinating Ctr, Seattle, WA 98195 USA. [Beach, Thomas G.] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ USA. [Bigio, Eileen H.] Northwestern Univ Feinberg, Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL USA. [Bigio, Eileen H.] Northwestern Univ Feinberg, Sch Med, Dept Pathol, Chicago, IL USA. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Frosch, Matthew] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Dept Pathol, Charlestown, MA USA. [Kofler, Julia] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Lee, Edward B.; Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Pittsburgh, PA USA. [Lee, Edward B.; Trojanowski, John Q.] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Pittsburgh, PA USA. [Lee, Edward B.; Trojanowski, John Q.] Univ Penn, Sch Med, Inst Aging, Pittsburgh, PA USA. [Nelson, Peter T.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Nelson, Peter T.] Univ Kentucky, Dept Pathol, Lexington, KY USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Vinters, Harry V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA 90095 USA. [Vinters, Harry V.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Vinters, Harry V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Hyman, Bradley T.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Charlestown, MA USA. [Sonnen, Joshua A.] Univ Utah, Dept Pathol, Salt Lake City, UT 84132 USA. RP Montine, TJ (reprint author), Univ Washington, Dept Pathol, Seattle, WA 98195 USA. EM tmontine@u.washington.edu FU National Institute on Aging, National Institutes of Health: National Alzheimer's Coordinating Center [U01 AG016976]; National Institute on Aging, National Institutes of Health: Alzheimer's Disease Centers [P50 AG05133, P50 AG05134, P50 AG05136, P50 AG05681, P30 AG10161, P30 AG10124, P30 AG13854, P50 AG16570, P30 AG19610, P30 AG28383, P01 AG03991] FX This work was supported by the following grants from the National Institute on Aging, National Institutes of Health: the, National Alzheimer's Coordinating Center (U01 AG016976), Alzheimer's Disease Centers (P50 AG05133, P50 AG05134, P50 AG05136, P50 AG05681, P30 AG10161, P30 AG10124, P30 AG13854, P50 AG16570, P30 AG19610, and P30 AG28383), and P01 AG03991. We thank Dr Kathleen Montine for editorial assistance. NR 15 TC 3 Z9 3 U1 1 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 FEB PY 2016 VL 12 IS 2 BP 164 EP 169 DI 10.1016/j.jalz.2015.07.492 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA DC9EI UT WOS:000369523500008 PM 26327235 ER PT J AU Ismail, Z Smith, EE Geda, Y Sultzer, D Brodaty, H Smith, G Aguera-Ortiz, L Sweet, R Miller, D Lyketsos, CG AF Ismail, Zahinoor Smith, Eric E. Geda, Yonas Sultzer, David Brodaty, Henry Smith, Gwenn Agueera-Ortiz, Luis Sweet, Rob Miller, David Lyketsos, Constantine G. CA ISTAART Neuropsychiat Symptoms Pro TI Neuropsychiatric symptoms as early manifestations of emergent dementia: Provisional diagnostic criteria for mild behavioral impairment SO ALZHEIMERS & DEMENTIA LA English DT Article DE Dementia; FTD; Alzheimer's disease; MCI; MBI; Neuropsychiatric symptoms of dementia; NPS; Behavior; Behaviour; Agitation; Psychosis; Disinhibition; Apathy; Depression; BPSD ID ALZHEIMERS ASSOCIATION WORKGROUPS; COGNITIVE IMPAIRMENT; FRONTOTEMPORAL DEMENTIA; NATIONAL INSTITUTE; CACHE COUNTY; RISK-FACTORS; DISEASE; PROGRESSION; AGITATION; PREDICTORS AB Neuropsychiatric symptoms (NPS) are common in dementia and in predementia syndromes such as mild cognitive impairment (MCI). NPS in MCI confer a greater risk for conversion to dementia in comparison to MCI patients without NPS. NPS in older adults with normal cognition also confers a greater risk of cognitive decline in comparison to older adults without NPS. Mild behavioral impairment (MBI) has been proposed as a diagnostic construct aimed to identify patients with an increased risk of developing dementia, but who may or may not have cognitive symptoms. We propose criteria that include MCI in the MBI framework, in contrast to prior definitions of MBI. Although MBI and MCI can co-occur, we suggest that they are different and that both portend a higher risk of dementia. These MBI criteria extend the previous literature in this area and will serve as a template for validation of the MBI construct from epidemiologic, neurobiological, treatment, and prevention perspectives. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Ismail, Zahinoor] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Ismail, Zahinoor; Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Ismail, Zahinoor] Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, Calgary, AB, Canada. [Ismail, Zahinoor; Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Geda, Yonas] Mayo Clin, Dept Psychiat, Scottsdale, AZ USA. [Geda, Yonas] Mayo Clin, Dept Neurol, Scottsdale, AZ USA. [Sultzer, David] VA Greater Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Sultzer, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Brodaty, Henry] Univ New S Wales, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. [Brodaty, Henry] Univ New S Wales, Dementia Collaborat Res Ctr, Sydney, NSW, Australia. [Smith, Gwenn] Johns Hopkins Sch Med, Alzheimers Dis Res Ctr, Baltimore, MD USA. [Agueera-Ortiz, Luis] Carlos III Inst Hlth, Alzheimer Ctr Reina Sofia Fdn, Res Unit, Madrid, Spain. [Agueera-Ortiz, Luis] CIBERSAM, Madrid, Spain. [Sweet, Rob] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Sweet, Rob] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sweet, Rob] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. [Miller, David] Bracket Global, Wayne, PA USA. [Lyketsos, Constantine G.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Ismail, Z (reprint author), Univ Calgary, Dept Psychiat, Calgary, AB, Canada.; Ismail, Z (reprint author), Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada.; Ismail, Z (reprint author), Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, Calgary, AB, Canada.; Ismail, Z (reprint author), Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. EM zahinoor@gmail.com FU Veterans Health Administration [BX000452]; NIH [MH071533, AG05133, AG027224, P50AG005146]; Department of Veterans Affairs FX The authors acknowledge The Alzheimer's Association ISTAART group for reading and supporting these criteria. Article supported in part by Veterans Health Administration Grant BX000452, and NIH grants MH071533, AG05133, AG027224 (R.S.), and P50AG005146 to the Johns Hopkins Alzheimer's Disease Research Center (C.G.L.) and by the Department of Veterans Affairs (D.S. and R.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Department of Veterans Affairs, or the United States Government. NR 52 TC 21 Z9 21 U1 1 U2 10 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 FEB PY 2016 VL 12 IS 2 BP 195 EP 202 DI 10.1016/j.jalz.2015.05.017 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DC9EI UT WOS:000369523500011 PM 26096665 ER PT J AU Wall, CR Stewart, AW Camargo, CA Scragg, R Mitchell, EA Ekeroma, A Crane, J Milne, T Rowden, J Horst, R Grant, CC AF Wall, Clare R. Stewart, Alistair W. Camargo, Carlos A., Jr. Scragg, Robert Mitchell, Edwin A. Ekeroma, Alec Crane, Julian Milne, Tania Rowden, Judy Horst, Ronald Grant, Cameron C. TI Vitamin D activity of breast milk in women randomly assigned to vitamin D-3 supplementation during pregnancy SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE breast milk; vitamin D; 25-hydroxyvitamin D; pregnancy; supplementation; infant feeding ID FED INFANTS; 25-HYDROXYVITAMIN-D; METABOLITES; LACTATION; CALCIUM AB Background: Human milk is typically low in vitamin D activity (VDA). Whether the vitamin D content of breast milk at birth can be increased by supplementing the mother during pregnancy has not been reported to the best of our knowledge. Objective: We examined the effect of vitamin D supplementation during pregnancy on breast-milk VDA in the first 2 mo of lactation. Design: Breast-milk samples were obtained from women who were enrolled in a randomized, double-blinded, placebo-controlled trial. of vitamin D supplementation during pregnancy. Pregnant women were enrolled at 27 wk of gestation and randomly assigned to the following 3 groups: a placebo group, a group who received one dosage of daily oral vitamin D-3 (1000 IU), or a group who received 2 dosages of daily oral vitamin D-3 (2000 IU). Serum 25-hydroxy-vitamin D [25(OH)D] was measured at enrollment, at 36 wk of gestation, and in cord blood at birth. Study participants who were breastfeeding were invited to provide breast-milk samples for VDA measurement [concentration of vitamin D-2, vitamin D-3, 25(OH)D-2, and 25(OH)D-3] at 2 wk and 2 mo postpartum. A linear mixed model was used to compare breast-milk VDA between the 3 study groups. Results: A total of 75 women provided breast-milk samples (44 women provided breast-milk samples at both 2 wk and 2 mo postpartum). The mean (95% CI) VDA at age 2 wk was 52 IU/L (12, 217 IU/L) in the placebo group, 51 IU/L (17, 151 IU/L) in the 1000-IU group, and 74 IU/L (25, 221 IU/L) in the 2000-IU group; and at age 2 mo, the mean (95% CI) VDA was 45 IU/L (16, 124 IU/L), 43 IU/L (18, 103 IU/L), and 58 IU/L (15, 224 IU/L), respectively. There was no significant interaction in VDA between the sample-collection time and treatment (P = 0.61), but there was a difference between lower- and higher-dosage treatment groups (P = 0.04). Conclusion: Maternal vitamin D supplementation during pregnancy of 2000 IU/d (compared with 1000 IU/d and with a placebo) results in a higher VDA of breast milk >= 2 mo postpartum. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12610000483055. C1 [Wall, Clare R.] Univ Auckland, Discipline Nutr & Dietet, Auckland 1, New Zealand. [Stewart, Alistair W.; Scragg, Robert] Univ Auckland, Sch Populat Hlth, Auckland 1, New Zealand. [Mitchell, Edwin A.; Milne, Tania; Rowden, Judy; Grant, Cameron C.] Univ Auckland, Dept Pediat Child & Youth Hlth, Auckland 1, New Zealand. [Ekeroma, Alec] Univ Auckland, Obstet & Gynecol, Auckland 1, New Zealand. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Med, Boston, MA USA. [Crane, Julian] Univ Otago, Med, Wellington, New Zealand. [Horst, Ronald] Heartland Assays LLC, Ames, IA USA. [Grant, Cameron C.] Auckland Dist Hlth Beard, Starship Childrens Hosp, Auckland, New Zealand. RP Wall, CR (reprint author), Univ Auckland, Discipline Nutr & Dietet, Auckland 1, New Zealand. EM c.wall@auck-land.ac.nz FU Health Research Council of New Zealand [09/215R]; University of Auckland Faculty Research Development Grant; Cure Kids FX Supported by the Health Research Council of New Zealand (grant number 09/215R). A University of Auckland Faculty Research Development Grant provided the additional funding required for the analyses of breast milk samples. EAM is supported by Cure Kids. NR 22 TC 2 Z9 2 U1 1 U2 6 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2016 VL 103 IS 2 BP 382 EP 388 DI 10.3945/ajcn.115.114603 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DC8JJ UT WOS:000369465400013 PM 26702121 ER PT J AU Mehta, AJ Cassidy, A Litonjua, AA Sparrow, D Vokonas, P Schwartz, J AF Mehta, Amar J. Cassidy, Aedin Litonjua, Augusto A. Sparrow, David Vokonas, Pantel Schwartz, Joel TI Dietary anthocyanin intake and age-related decline in lung function: longitudinal findings from the VA Normative Aging Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE anthocyanins; clinical epidemiology; diet; flavonoids; lung function tests ID OBSTRUCTIVE PULMONARY-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; NF-KAPPA-B; OXIDATIVE STRESS; VENTILATORY FUNCTION; AIRWAY INFLAMMATION; GENERAL-POPULATION; CONTROLLED-TRIAL; NATIONAL-HEALTH; GLOBAL BURDEN AB Background: It is unknown whether habitual intake of dietary flavonoids, known for their antioxidative and anti-inflammatory properties, affects longitudinal change in lung function. Objective: We investigated whether different flavonoid subclasses present in the habitual diet were associated with beneficial changes in lung function over time in the elderly. Design: This longitudinal analysis included 839 participants from the VA (Veterans Affairs) Normative Aging Study whose lung function [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] was measured at 2 and up to 5 visits between 1992 and 2008 (n = 2623 measurements). Yearly average intake of major flavonoid subclasses (anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polymers) was calculated from food-frequency questionnaires at each visit. We estimated adjusted differences in annual change in lung function associated with each flavonoid subclass, categorized into quartiles, in linear mixed-effects regression models after adjustment for lifestyle and dietary confounders. Results: Strong inverse associations were found between anthocyanin intake and age-related decline in lung function. Independent of dietary and nondietary risk factors, slower rates of FEV1 and FVC decline by 23.6 (95% CI: 16.6, 30.7) and 37.3 (95% CI: 27.8, 46.8) mIJy, respectively, were observed in participants in the fourth quartile of intake compared with participants in the first quartile (P-trend < 0.0001). The protective associations observed for anthocyanin intake were present in both current/former and never smokers. Compared with no or very low intakes, an intake of >= 2 servings of anthocyanin-rich bluebenies/wk was associated with slower decline in FEV1 and FVC by 22.5 (95% CI: 10.8, 34.2) and 37.9 (95% CI: 22.1, 53.7) mL/y, respectively. To a lesser extent, higher flavan-3-ol intake was also associated with slower lung function decline. Conclusions: An attenuation of age-related lung function decline was associated with higher dietary anthocyanin intake in this longitudinal sample of predominantly elderly men. Further prospective studies are needed to confirm these novel associations. C1 [Mehta, Amar J.; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Cassidy, Aedin] Univ E Anglia, Norwich Med Sch, Dept Nutr, Norwich NR4 7TJ, Norfolk, England. [Litonjua, Augusto A.; Sparrow, David] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Litonjua, Augusto A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Sparrow, David; Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Sparrow, David; Vokonas, Pantel] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Mehta, AJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM amehta@hsph.harvard.edu FU National Institute of Environmental Health Sciences [ES014663-01A2]; US Environmental Protection Agency [EPA R832416, R827353, R83241601]; Cooperative Studies Program/Epidemiology Research and Information Center of the US Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts; NIH [R01-AG002287, R01-AG018436, R29-AG007465]; VA Research Career Scientist award; Royal Society Wolfson Research Merit Award; UK Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J004545/1] FX Supported by the grants from the National Institute of Environmental Health Sciences (ES014663-01A2) and from the US Environmental Protection Agency (EPA R832416, R827353, and R83241601). The VA (Veterans Affairs) Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts. Support was also provided by NIH grants R01-AG002287, R01-AG018436, and R29-AG007465. This research was also supported by a VA Research Career Scientist award to DS, a Royal Society Wolfson Research Merit Award, and UK Biotechnology and Biological Sciences Research Council funding (BBSRC reference BB/J004545/1) to AC. This is an open access article distributed under the CC-BY license (http://creativecommons.org/licenses/by/3.0/). NR 58 TC 4 Z9 4 U1 3 U2 8 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2016 VL 103 IS 2 BP 542 EP 550 DI 10.3945/ajcn.115.121467 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DC8JJ UT WOS:000369465400030 PM 26791184 ER PT J AU Castillo, JJ Mulkey, F Geyer, S Kolitz, JE Blum, W Powell, BL George, SL Larson, RA Stone, RM AF Castillo, Jorge J. Mulkey, Flora Geyer, Susan Kolitz, Jonathan E. Blum, William Powell, Bayard L. George, Stephen L. Larson, Richard A. Stone, Richard M. TI Relationship between obesity and clinical outcome in adults with acute myeloid leukemia: A pooled analysis from four CALGB (alliance) clinical trials SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; BODY-MASS INDEX; DIFFERENTIATION SYNDROME; PROGNOSTIC-FACTORS; DOSE CHEMOTHERAPY; OVERWEIGHT; IMPACT; METAANALYSIS; MORTALITY AB Obesity has been previously suggested as an adverse prognostic marker in patients with acute leukemia. To evaluate the relationship between obesity and clinical outcome, disease-free survival (DFS) and overall survival (OS), in patients with acute myelogenous leukemia (AML), including acute promyelocytic leukemia (APL), we performed a pooled analysis of four CALGB (Alliance) clinical trials. Our study included 446 patients with APL from CALGB 9710, and 1,648 patients between 18 and 60 years of age with non-APL AML from CALGB 9621, 10503, and 19808. Obesity was defined as BMI >= 30 kg/m(2). Multivariate Cox proportional-hazard regression models were fitted for DFS and OS. Obesity was seen in 50% and 38% of APL and non-APL AML patients, respectively. In APL patients, obesity was associated with worse DFS (HR 1.53, 95% CI 1.03-2.27; P = 0.04) and OS (HR 1.72, 95% CI 1.15-2.58; P = 01) after adjusting for age, sex, performance status, race, ethnicity, treatment arm and baseline white blood cell count. Obesity was not significantly associated with DFS or OS in the non-APL AML patients. In conclusion, our study indicates that obesity has significant prognostic value for DFS and OS in APL patients, but not for non-APL AML patients. (C) 2015 Wiley Periodicals, Inc. C1 [Castillo, Jorge J.; Stone, Richard M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. [Mulkey, Flora; George, Stephen L.] Duke Univ, Alliance Stat & Data Ctr, Durham, NC USA. [Geyer, Susan] Univ S Florida, Hlth Informat Inst, Tampa, FL USA. [Kolitz, Jonathan E.] Monter Canc Ctr, Lake Success, NY USA. [Blum, William] Ohio State Univ, Ctr Comprehens Canc, Div Hematol, Columbus, OH 43210 USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Sect Hematol & Oncol, Winston Salem, NC 27109 USA. [Larson, Richard A.] Univ Chicago, Ctr Comprehens Canc, Sect Hematol & Oncol, Chicago, IL 60637 USA. RP Castillo, JJ (reprint author), 450 Brookline Ave,M221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Larson, Richard/0000-0001-9168-3203; Castillo, Jorge/0000-0001-9490-7532 FU National Cancer Institute of the National Institutes of Health [U10CA180821, U10CA180882] FX Contract grant sponsor: National Cancer Institute of the National Institutes of Health; Contract grant numbers: U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology). NR 30 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 2016 VL 91 IS 2 BP 199 EP 204 DI 10.1002/ajh.24230 PG 6 WC Hematology SC Hematology GA DC7WG UT WOS:000369430800014 PM 26526191 ER PT J AU Cohen, SL Morris, SN Brown, DN Greenberg, JA Walsh, BW Gargiulo, AR Isaacson, KB Wright, KN Srouji, SS Anchan, RM Vogell, AB Einarsson, JI AF Cohen, Sarah L. Morris, Stephanie N. Brown, Doug N. Greenberg, James A. Walsh, Brian W. Gargiulo, Antonio R. Isaacson, Keith B. Wright, Kelly N. Srouji, Serene S. Anchan, Raymond M. Vogell, Alison B. Einarsson, Jon I. TI Contained tissue extraction using power morcellation: prospective evaluation of leakage parameters SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE hysterectomy; in-bag morcellation; laparoscopic surgery; myomectomy ID LAPAROSCOPIC SUPRACERVICAL HYSTERECTOMY; QUALITY-OF-LIFE; UTERINE LEIOMYOSARCOMA; ABDOMINAL HYSTERECTOMY; CONTROLLED-TRIAL; SURGERY; MYOMECTOMY; SARCOMA; IMPACT; BAG AB BACKGROUND: Safe tissue removal is a challenge for minimally invasive procedures such as myomectomy, supracervical hysterectomy, or total hysterectomy of a large uterine specimen. There is concern regarding disruption or dissemination of tissue during this process, which may be of particular significance in cases of undetected malignancy. Contained tissue extraction techniques have been developed in an effort to mitigate morcellation-related risks. OBJECTIVE: The objective of the study was to quantify perioperative outcomes of contained tissue extraction using power morcellation, specifically evaluating parameters of tissue or fluid leakage from within the containment system. STUDY DESIGN: This was a study including a multicenter prospective cohort of adult women who underwent minimally invasive hysterectomy or myomectomy using a contained power morcellation technique. Blue dye was applied to the tissue specimen prior to removal to help identify cases of fluid or tissue leakage from within the containment system. RESULTS: A total of 76 patients successfully underwent the contained power morcellation protocol. Mean time for the contained morcellation procedure was 30.2 minutes (+/- 22.4). The mean hysterectomy specimen weight was 480.1 g (+/- 359.1), and mean myomectomy specimen weight was 239.1 g (+/- 229.7). The vast majority of patients (73.7%) were discharged home the same day of surgery. Final pathological diagnosis was benign in all cases. Spillage of dye or tissue was noted in 7 cases (9.2%), although containment bags were intact in each of these instances. CONCLUSION: Findings are consistent with prior work demonstrating the feasibility of contained tissue extraction; however, further refinement of this technique is warranted. C1 [Cohen, Sarah L.; Einarsson, Jon I.] Brigham & Womens Hosp, Div Minimally Invas Gynecol Surg, 75 Francis St, Boston, MA 02115 USA. [Walsh, Brian W.; Gargiulo, Antonio R.; Srouji, Serene S.; Anchan, Raymond M.] Brigham & Womens Hosp, Div Reprod Endocrinol & Infertil, 75 Francis St, Boston, MA 02115 USA. [Morris, Stephanie N.; Isaacson, Keith B.] Newton Wellesley Hosp, Div Minimally Invas Gynecol Surg, Newton, MA USA. [Brown, Doug N.] Massachusetts Gen Hosp, Ctr Minimally Invas Gynecol Surg, Boston, MA 02114 USA. [Greenberg, James A.] Brigham & Womens Faulkner Hosp, Dept Gynecol, Boston, MA USA. [Wright, Kelly N.; Vogell, Alison B.] Lahey Hosp & Med Ctr, Dept Gynecol, Burlington, MA USA. RP Cohen, SL (reprint author), Brigham & Womens Hosp, Div Minimally Invas Gynecol Surg, 75 Francis St, Boston, MA 02115 USA. EM scohen20@partners.org NR 22 TC 5 Z9 5 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2016 VL 214 IS 2 AR 257.e1-e6 DI 10.1016/j.ajog.2015.08.076 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DC9CJ UT WOS:000369518200013 PM 26348384 ER PT J AU Gordon, MC McKenna, DS Stewart, TL Howard, BC Foster, KF Higby, K Cypher, RL Barth, WH AF Gordon, Michael C. McKenna, David S. Stewart, Theresa L. Howard, Bobby C. Foster, Kimberly F. Higby, Kenneth Cypher, Rebecca L. Barth, William H. TI Transvaginal cervical length scans to prevent prematurity in twins: a randomized controlled trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE prematurity prevention; transvaginal cervical length; twins ID PRETERM BIRTH; GESTATIONS; PREDICTION; ULTRASONOGRAPHY; PROGESTERONE; METAANALYSIS; PREGNANCIES; CERCLAGE; WOMEN; RISK AB BACKGROUND: Twin pregnancies are associated with an increased risk of perinatal morbidity and mortality primarily due to spontaneous preterm deliveries. The mean gestational age for delivery is 35.3 weeks and twins account for 23% of preterm births < 32 weeks. A number of strategies have been proposed to prevent preterm deliveries: tocolytics, bed rest, hospitalization, home uterine activity monitoring, cerclage, and most recently, progesterone. Unfortunately, none have proven effective. Recent metaanalyses and reviews suggest that transvaginal cervical length (TVCL) ultrasound in the second trimester is a powerful predictor of preterm birth among asymptomatic women. Indeed, TVCL has the highest positive and negative predictive values for determining the risk of spontaneous preterm delivery in twin pregnancies. It follows that TVCL assessment may allow identification of a subset of twin pregnancies that re better candidates for interventions intended to prevent prematurity. OBJECTIVE: We sought to determine whether use of TVCL prolongs gestation in twin pregnancies. STUDY DESIGN: This is a multicenter, randomized, controlled trial of 125 dichorionic or monochorionic/diamniotic twin pregnancies without prior preterm birth < 28 weeks. The study group (n = 63) had TVCL and digital exams monthly from 16-28 weeks and were managed with a standard algorithm for activity restriction and cerclage. The control group (n = 62) had monthly digital cervical examinations but no routine TVCL ultrasound examinations. The primary outcome was gestational age at delivery. Secondary outcomes included percentage of deliveries < 35 weeks, and maternal and neonatal outcomes. RESULTS: The mean gestational age at delivery was 35.7 weeks (95% confidence interval [CI], 35.2-36.2) among those managed with TVCL and 35.5 weeks (95% CI, 34.7-36.4) among the control patients. The Kaplan-Meier estimates of deliveries < 38 weeks were not significantly different between groups. This was true whether we compared curves with a log-rank test (P =.67), Breslow test (P =.67), or Tarone-Ware test (P =.64). The percentage of deliveries < 35 0/7 weeks did not differ: 27.4% for subjects managed with routine TVCL and 28.6% for control subjects (relative risk, 0.96; 95% CI, 0.60-1.54). Our study had an 80% power to detect a 12-day difference in the gestational age at delivery with 95% confidence. CONCLUSION: The overall mean length of gestation and the percentage of women delivering < 35 weeks did not differ between twin gestations managed with TVCL and digital exams monthly from 16-28 weeks with a standard algorithm for activity restriction and cerclage and controls who had monthly digital cervical examinations but no routine TVCL. Routine second-trimester transvaginal ultrasound assessment of cervical length is not associated with improved outcomes when incorporated into the standard management of otherwise low-risk twin pregnancies. C1 [Gordon, Michael C.; Stewart, Theresa L.; Cypher, Rebecca L.; Barth, William H.] Wilford Hall USAF Med Ctr, Dept Obstet & Gynecol, Lackland AFB, TX USA. [McKenna, David S.; Foster, Kimberly F.] Wright Patterson Med Ctr, Dept Obstet & Gynecol, Wright Patterson AFB, OH USA. [McKenna, David S.] Wright State Univ, Dayton, OH 45435 USA. [Howard, Bobby C.] Madigan Army Med Ctr, Dept Obstet & Gynecol, Tacoma, WA 98431 USA. [Howard, Bobby C.] Univ Tennessee, Med Ctr, Dept Obstet & Gynecol, Knoxville, TN USA. [Higby, Kenneth] Ctr Maternal Fetal Care, San Antonio, TX USA. [Barth, William H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Div Maternal Fetal Med, Boston, MA USA. RP Gordon, MC (reprint author), Wilford Hall USAF Med Ctr, Dept Obstet & Gynecol, Lackland AFB, TX USA. EM packergord@aol.com NR 18 TC 3 Z9 3 U1 2 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2016 VL 214 IS 2 AR 277.e1-e7 DI 10.1016/j.ajog.2015.08.065 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DC9CJ UT WOS:000369518200026 PM 26363481 ER PT J AU Jakobiec, FA AF Jakobiec, Frederick A. TI Conjunctival Primary Acquired Melanosis: Is It Time for a New Terminology? SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MALIGNANT MELANOCYTIC LESIONS; IN-SITU HYBRIDIZATION; SINE PIGMENTO; NEVI; EXPRESSION; FEATURES; BENIGN; CLASSIFICATION; CRYOTHERAPY; EXPERIENCE AB PURPOSE: To review the diagnostic categories of a group of conditions referred to as "primary acquired melanosis." DESIGN: Literature review on the subject and proposal of an alternative diagnostic schema with histopathologic and immunohistochemical illustrations. METHODS: Standard hematoxylin-eosin-stained sections and immunohistochemical stains for MART-1, HMB-45, microphthalmia-associated transcriptioniactor (MiTF), and Ki-67 for calculating the proliferation index are illustrated. RESULTS: "Melanosis" is an inadequate and misleading term because it does not distinguish between conjunctival intraepithelial melanin overproduction ("hyperpigmentation") and intraepithelial melanocytic proliferation. It is recommended that "intraepithelial melanocytic proliferation" be adopted for histopathologic diagnosis. Atypical proliferations are characterized either by bloated dendritic melanocytes with enlarged cell components (dendrites, cell bodies, and nuclei) or by epithelioid melanocytes without dendrites. Atypical polygonal or epithelioid pagetoid cells may reach higher levels of the epithelium beyond the basal layer. Immunohistochemistry defines the degree of melanocytic proliferation or the cellular shape (dendritic or nondendritic) (MART-1, HMB-45) or identifies the melanocytic nuclei (MiTF). Intraepithelial melanocytic proliferation without atypia represents increased numbers of normal-appearing dendritic melanocytes (hyperplasia or early neoplasia) that generally remain confined to the basal/basement membrane region. Intraepithelial nonproliferative melanocytic pigmentation signifies the usually small number of conjunctival basal dendritic melanocytes that synthesize increased amounts of melanin that is transferred to surrounding keratinocytes. CONCLUSION: All pre- and postoperative biopsies of flat conjunctival melanocytic disorders should be evaluated immunohistochemically if there is any question regarding atypicality. This should lead to a clearer microscopic descriptive diagnosis that is predicated on an analysis of the participating cell types and their architectural patterns. This approach is conducive to a better appreciation of features indicating when to intervene therapeutically. An accurate early diagnosis should forestall unnecessary later. surgery. (C) 2016 by Elsevier Inc. All rights reserved. C1 [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St Room 328, Boston, MA 02114 USA. [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Jakobiec, Frederick A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St Room 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 62 TC 4 Z9 4 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2016 VL 162 BP 3 EP 19 DI 10.1016/j.ajo.2015.11.003 PG 17 WC Ophthalmology SC Ophthalmology GA DC8JU UT WOS:000369466500002 PM 26556007 ER PT J AU Rudnisky, CJ Belin, MW Guo, R Ciolino, JB AF Rudnisky, Christopher J. Belin, Michael W. Guo, Rong Ciolino, Joseph B. CA Boston Type 1 Keratoprosthesis TI Visual Acuity Outcomes of the Boston Keratoprosthesis Type 1: Multicenter Study Results SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID COUNTING FINGERS; HAND MOTION; GLAUCOMA; ENDOPHTHALMITIS; COMPLICATIONS; CATEGORIES; VISION AB PURPOSE: To report logarithm of the minimal angle of resolution (logMAR) visual outcomes of the Boston keratoprosthesis type 1. DESIGN: Prospective cohort study. METHODS: Preoperative, intraoperative, and postoperative parameters of 300 eyes of 300 patients who underwent implantation of a Boston keratoprosthesis type 1 device between January 2003 and July 2008 by 1 of 19 surgeons at 18 medical centers were collected. RESULTS: After an average of 17.1 +/- 14.8 months, visual acuity improved significantly (P < .0001) to a mean final value of 0.89 +/- 0.64 (20/150). There were also significantly fewer eyes with light perception (6.7%; n = 19; P < .0001), although 3.1% (n = 9) progressed to no light perception. There was no association between age (P = .08), sex (P = .959), operative side (P = .167), or failure (P = .494) and final visual acuity. The median time to achieve 20/200 visual acuity was 1 month (95% confidence interval 1.0-6.0) and it was retained for an average of 47.8 months. Multivariate analysis, controlling for preoperative visual acuity, demonstrated 2 factors associated with final visual outcome: chemical injury was associated with better final vision (P = .007), whereas age-related macular degeneration was associated with poorer vision (P < .0001). CONCLUSIONS: The Boston keratoprosthesis type 1 is an effective device for rehabilitation in advanced ocular surface disease, resulting in a significant improvement in visual acuity. Eyes achieved a mean value of 20/150 (0.89 0.64 IogMAR units) after 6 months and this was relatively stable thereafter. The best visual prognosis is observed in chemical injury eyes, whereas the worst prognosis is in aniridia, although the latter has limited visual potential. (C) 2016 by Elsevier Inc. All rights reserved. C1 [Rudnisky, Christopher J.] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada. [Belin, Michael W.] Univ Arizona, Dept Ophthalmol & Vis Sci, Tucson, AZ USA. [Guo, Rong; Ciolino, Joseph B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Ciolino, JB (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Joseph_Ciolino@meei.harvard.edu FU NEI, BETHESDA, MARYLAND, USA [1K08EY019686-01]; Research to Prevent Blindness, Inc, New York, New York; Alcon, Fort Worth, Texas, USA; Bausch & Lomb, Rochester, New York, USA; Glaucoma Research Society of Canada, East York, Ontario, Canada; National Institutes of Health, Bethesda, Maryland, USA; Research to Prevent Blindness, New York, New York, USA FX THIS RESEARCH WAS FUNDED BY NEI 1K08EY019686-01, BETHESDA, MARYLAND, USA (J.B.C.) AND A Career Development Award from Research to Prevent Blindness, Inc, New York, New York (J.B.C.). Financial disclosures: Chris J. Rudnisky: Alcon, Fort Worth, Texas, USA (speaking fees); Bausch & Lomb, Rochester, New York, USA (speaking fees); Glaucoma Research Society of Canada, East York, Ontario, Canada (grant); Novartis, Basel, Switzerland (stock).; Merck, Kenilworth, New Jersey, USA (stock). Michael W. Belin: Oculus, Wetzlar, Germany (consultancy); Joseph B. Ciolino: ORA, Andover, Massachusetts, USA (consultancy); Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA (employment); National Institutes of Health, Bethesda, Maryland, USA (grant support); Research to Prevent Blindness, New York, New York, USA (grant support). The following author has no financial disclosures: Rong Guo. All authors attest that they meet the current ICMJE criteria for authorship. NR 25 TC 2 Z9 2 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2016 VL 162 BP 89 EP 98 DI 10.1016/j.ajo.2015.10.023 PG 10 WC Ophthalmology SC Ophthalmology GA DC8JU UT WOS:000369466500012 PM 26550696 ER PT J AU Feemster, LC Curtis, JR AF Feemster, Laura C. Curtis, J. Randall TI "We Understand the Prognosis, but We Live with Our Heads in the Clouds": Understanding Patient and Family Outcome Expectations and Their Influence on Shared Decision Making SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID ADVANCED CANCER; COMMUNICATION; PREFERENCES C1 [Feemster, Laura C.] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA USA. [Feemster, Laura C.; Curtis, J. Randall] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Curtis, J. Randall] Univ Washington, Cambia Palliat Care Ctr Excellence, Seattle, WA 98195 USA. RP Feemster, LC (reprint author), VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA USA.; Feemster, LC (reprint author), Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. FU NHLBI NIH HHS [HL111116, K23 HL111116] NR 14 TC 0 Z9 0 U1 4 U2 4 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 FEB 1 PY 2016 VL 193 IS 3 BP 239 EP 241 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DC6UR UT WOS:000369355600008 PM 26829423 ER PT J AU Kellum, JA Chawla, LS Keener, C Singbartl, K Palevsky, PM Pike, FL Yealy, DM Huang, DT Angus, DC AF Kellum, John. A. Chawla, Lakhmir S. Keener, Christopher Singbartl, Kai Palevsky, Paul M. Pike, Francis L. Yealy, Donald M. Huang, David T. Angus, Derek C. CA ProCESS & ProGReSS-AKI Investigato TI The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE sepsis; septic shock; resuscitation; early goal-directed therapy; acute kidney injury ID CRITICALLY-ILL PATIENTS; CREATININE; MORTALITY; RECOVERY; CRITERIA; TRIAL; CARE AB Rationale: Septic shock is a common cause of acute kidney injury (AKI), and fluid resuscitation is a major part of therapy. Objectives: To determine if structured resuscitation designed to alter fluid, blood, and vasopressor use affects the development or severity of AKI or outcomes. Methods: Ancillary study to the ProCESS (Protocolized Care for Early Septic Shock) trial of alternative resuscitation strategies (two protocols vs. usual care) for septic shock. Measurements and Main Results: We studied 1,243 patients and classified AKI using serum creatinine and urine output. We determined recovery status at hospital discharge, examined rates of renal replacement therapy and fluid overload, and measured biomarkers of kidney damage. Among patients without evidence of AKI at enrollment, 37.6% of protocolized care and 38.1% of usual care patients developed kidney injury (P = 0.90). AKI duration (P = 0.59) and rates of renal replacement therapy did not differ between study arms (6.9% for protocolized care and 4.3% for usual care; P = 0.08). Fluid overload occurred in 8.3% of protocolized care and 6.3% of usual care patients (P = 0.26). Among patients with severe AKI, complete and partial recovery was 50.7 and 13.2% for protocolized patients and 49.1 and 13.4% for usual care patients (P = 0.93). Sixty-day hospital mortality was 6.2% for patients without AKI, 16.8% for those with stage 1, and 27.7% for stages 2 to 3. Conclusions: In patients with septic shock, AKI is common and associated with adverse outcomes, but it is not influenced by protocolized resuscitation compared with usual care. C1 [Kellum, John. A.; Pike, Francis L.; Huang, David T.; Angus, Derek C.] Univ Pittsburgh, Dept Crit Care Med, CRISMA Ctr, Pittsburgh, PA 15261 USA. [Kellum, John. A.; Chawla, Lakhmir S.; Singbartl, Kai; Palevsky, Paul M.] Univ Pittsburgh, Ctr Crit Care Nephrol, Pittsburgh, PA 15261 USA. [Keener, Christopher] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Palevsky, Paul M.] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, 930 Scaife Hall, Pittsburgh, PA 15261 USA. [Yealy, Donald M.] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA 15261 USA. [Chawla, Lakhmir S.] Vet Affairs Med Ctr, Dept Med, Div Intens Care Med, 50 Irving St NW, Washington, DC 20422 USA. [Chawla, Lakhmir S.] Vet Affairs Med Ctr, Div Nephrol, 50 Irving St NW, Washington, DC 20422 USA. [Singbartl, Kai] Penn State Hershey Med Ctr, Dept Anesthesia, Hershey, PA USA. [Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Med Serv, Renal Sect, Pittsburgh, PA USA. RP Kellum, JA (reprint author), Univ Pittsburgh, Dept Crit Care Med, 3550 Terrace St,604 Scaife Hall, Pittsburgh, PA 15261 USA. EM kellumja@ccm.upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases grant [R01 DK083961]; NIH/National Institute of General Medical Sciences grant [P50 GM076659] FX Supported by National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases grant R01 DK083961 and NIH/National Institute of General Medical Sciences grant P50 GM076659. NR 19 TC 11 Z9 11 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2016 VL 193 IS 3 BP 281 EP 287 DI 10.1164/rccm.201505-0995OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DC6UR UT WOS:000369355600013 PM 26398704 ER PT J AU Pugmire, BS Shailam, R Sagar, P Liu, B Li, XH Palmer, WE Huang, AJ AF Pugmire, Brian S. Shailam, Randheer Sagar, Pallavi Liu, Bob Li, Xinhua Palmer, William E. Huang, Ambrose J. TI Initial Clinical Experience With Extremity Cone-Beam CT of the Foot and Ankle in Pediatric Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cone-beam CT; musculoskeletal imaging; pediatric imaging; radiation dose ID COMPUTED-TOMOGRAPHY; IMAGING TECHNIQUE; WEIGHT-BEARING; CBCT; SYSTEM; WRIST; MSCT AB OBJECTIVE. Extremity cone-beam CT (CBCT) scanners have become available for clinical use in the United States. The purpose of this study was to review an initial clinical experience with CBCT of the foot and ankle in pediatric patients. MATERIALS AND METHODS. A retrospective review was conducted of all foot or ankle CBCT examinations performed on patients 18 years old and younger at one institution from August 1, 2013, through February 28, 2015. A t test was used to compare mean effective dose for CBCT with that for MDCT foot or ankle examinations of age-matched control subjects. To assess changes in utilization, a t test also was used to compare the mean numbers of foot or ankle CT examinations per month before and after installation of the CBCT scanner at the institution. RESULTS. Thirty-four CBCT examinations were performed. The mean effective dose was 0.013 +/- 0.003 mSv compared with 0.023 +/- 0.020 mSv for MDCT of age-matched control subjects (p < 0.005). The mean numbers of foot or ankle CT examinations per month were 3.4 in the 18 months before and 3.8 in the 18 months after installation of the CBCT scanner (p = 0.28). The mean number of foot or ankle MDCT examinations per month decreased significantly (3.4 vs 1.9, p = 0.03) over the same period. In 56% of patients, CBCT revealed important findings that were not visible on contemporaneous radiographs. In 68% of patients, the CBCT findings affected clinical management. CONCLUSION. CBCT of the foot or ankle of pediatric patients is a viable lower-dose alternative to MDCT that provides important information that may affect clinical management. C1 [Pugmire, Brian S.; Palmer, William E.; Huang, Ambrose J.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. [Shailam, Randheer; Sagar, Pallavi] Massachusetts Gen Hosp, Dept Radiol, Div Pediat Imaging, Boston, MA 02114 USA. [Liu, Bob; Li, Xinhua] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Huang, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM ajhuang@mgh.harvard.edu NR 31 TC 0 Z9 0 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2016 VL 206 IS 2 BP 431 EP 435 DI 10.2214/AJR.15.15099 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DC9PH UT WOS:000369553000047 PM 26797374 ER PT J AU Platts-Mills, TF Flannigan, SA Bortsov, AV Smith, S Domeier, RM Swor, RA Hendry, PL Peak, DA Rathlev, NK Jones, JS Lee, DC Keefe, FJ Sloane, PD McLean, SA AF Platts-Mills, Timothy F. Flannigan, Sean A. Bortsov, Andrey V. Smith, Samantha Domeier, Robert M. Swor, Robert A. Hendry, Phyllis L. Peak, David A. Rathlev, Niels K. Jones, Jeffrey S. Lee, David C. Keefe, Francis J. Sloane, Philip D. McLean, Samuel A. TI Persistent Pain Among Older Adults Discharged Home From the Emergency Department After Motor Vehicle Crash: A Prospective Cohort Study SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID WHIPLASH-ASSOCIATED DISORDERS; PERITRAUMATIC DISTRESS INVENTORY; HAND-HELD DYNAMOMETRY; MUSCULOSKELETAL PAIN; PRIMARY-CARE; FUNCTIONAL DECLINE; NONCANCER PAIN; UNITED-STATES; NECK PAIN; COLLISION AB Study objective: Motor vehicle crashes are the second most common form of trauma among older adults. We seek to describe the incidence, risk factors, and consequences of persistent pain among older adults evaluated in the emergency department (ED) after a motor vehicle crash. Methods: We conducted a prospective longitudinal study of patients aged 65 years or older who presented to one of 8 EDs after motor vehicle crash between June 2011 and June 2014 and were discharged home after evaluation. ED evaluation was done through in-person interview; follow-up data were obtained through mail-in survey or telephone call. Pain severity (0 to 10 scale) overall and for 15 parts of the body were assessed at each follow-up point. Principal component analysis was used to assess the dimensionality of the locations of pain data. Participants reporting pain severity greater than or equal to 4 attributed to the motor vehicle crash at 6 months were defined as having persistent pain. Results: Of the 161 participants, 72% reported moderate to severe pain at the ED evaluation. At 6 months, 26% of participants reported moderate to severe motor vehicle crash-related pain. ED characteristics associated with persistent pain included acute pain severity; pain located in the head, neck, and jaw or lower back and legs; poor self rated health; less formal education; pre-motor vehicle crash depressive symptoms; and patient's expected time to physical recovery more than 30 days. Compared with individuals without persistent pain, those with persistent pain were substantially more likely at 6-month follow-up to have also experienced a decline in their capacity for physical function (73% versus 36%; difference=37%; 95% confidence interval [CI] 19% to 52%), a new difficulty with activities of daily living (42% versus 17%; difference=26%; 95% CI 10% to 43%), a 1-point or more reduction in overall self-rated health on a 5-point scale (54% versus 30%; difference=24%; 95% CI 6% to 41%), and a change in their living situation to obtain additional help (23% versus 8%; difference=15%; 95% CI 2% to 31%). Conclusion: Among older adults discharged home from the ED post-evaluation after a motor vehicle crash, persistent pain is common and frequently associated with functional decline and disability. C1 [Platts-Mills, Timothy F.; Flannigan, Sean A.; Smith, Samantha; McLean, Samuel A.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC USA. [Platts-Mills, Timothy F.; Bortsov, Andrey V.; McLean, Samuel A.] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC USA. [Sloane, Philip D.] Univ N Carolina, Dept Family Med, Chapel Hill, NC 27514 USA. [Domeier, Robert M.] St Joseph Mercy Hosp, Dept Emergency Med, Ypsilanti, MI USA. [Swor, Robert A.] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA. [Hendry, Phyllis L.] Univ Florida Hlth, Dept Emergency Med, Jacksonville, FL USA. [Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Jones, Jeffrey S.] Spectrum Hlth, Grand Rapids, MI USA. [Lee, David C.] North Shore Hosp Syst, Dept Emergency Med, Manhasset, NY USA. [Keefe, Francis J.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. RP Platts-Mills, TF (reprint author), Univ N Carolina, Dept Emergency Med, Chapel Hill, NC USA.; Platts-Mills, TF (reprint author), Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC USA. EM tplattsm@med.unc.edu OI McLean, Samuel/0000-0001-9482-3582 FU National Institute on Aging [K32AG038548] FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist and provided the following details: This study was supported by National Institute on Aging grant K32AG038548 (to Dr. Platts-Mills). NR 56 TC 6 Z9 6 U1 2 U2 8 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 FEB PY 2016 VL 67 IS 2 BP 166 EP 176 DI 10.1016/j.annemergmed.2015.05.003 PG 11 WC Emergency Medicine SC Emergency Medicine GA DC3MW UT WOS:000369124400007 PM 26092559 ER PT J AU Calcagno, C Mulder, WJM Nahrendorf, M Fayad, ZA AF Calcagno, Claudia Mulder, Willem J. M. Nahrendorf, Matthias Fayad, Zahi A. TI Systems Biology and Noninvasive Imaging of Atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; cardiovascular diseases; inflammation; lipids; risk factors ID CORONARY-ARTERY-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; INTIMA-MEDIA THICKNESS; URINARY PROTEOMIC BIOMARKERS; GENOME-WIDE ASSOCIATION; CONTRAST-ENHANCED MRI; GENETIC RISK SCORE; CELL LUNG-CANCER; CARDIOVASCULAR-DISEASE; HEART-DISEASE C1 [Calcagno, Claudia; Mulder, Willem J. M.; Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Mulder, Willem J. M.] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Nahrendorf, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. RP Calcagno, C (reprint author), Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. EM claudia.calcagno@mssm.edu FU Harold S. Geneen Charitable Trust Award [R01 EB009638, R01 HL071021, R01 HL118440, R01 HL125703]; NWO Vidi FX This work was supported by R01 EB009638 (Z.A.F.), R01 HL071021 (Z.A.F., C.C.), R01 HL118440 (W.J.M.M.), R01 HL125703 (W.J.M.M.), Harold S. Geneen Charitable Trust Award (Z.A.F.); NWO Vidi (W.J.M.M.). NR 129 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2016 VL 36 IS 2 BP E1 EP E8 DI 10.1161/ATVBAHA.115.306350 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DC8PZ UT WOS:000369483400001 PM 26819466 ER PT J AU Sevy, S Sher, L AF Sevy, Serge Sher, Leo TI Gender differences in the dosing of antipsychotic medications SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Sevy, Serge; Sher, Leo] James J Peters VA Med Ctr, 130 West Kingsbridge Rd, New York, NY 10468 USA. [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. RP Sevy, S (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd, New York, NY 10468 USA. EM sevymd@gmail.com NR 3 TC 0 Z9 0 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD FEB PY 2016 VL 50 IS 2 SI SI BP 185 EP 186 DI 10.1177/0004867415609426 PG 3 WC Psychiatry SC Psychiatry GA DC5FQ UT WOS:000369247300022 PM 26450940 ER PT J AU Walters, MC De Castro, LM Sullivan, KM Krishnamurti, L Kamani, N Bredeson, C Neuberg, D Hassell, KL Farnia, S Campbell, A Petersdorf, E AF Walters, Mark C. De Castro, Laura M. Sullivan, Keith M. Krishnamurti, Lakshmanan Kamani, Naynesh Bredeson, Christopher Neuberg, Donna Hassell, Kathryn L. Farnia, Stephanie Campbell, Andrew Petersdorf, Effie TI Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Sickle cell anemia; Hematopoietic cell transplant; HLA-identical sibling; Transplant-related complications; Risks; Children ID BONE-MARROW-TRANSPLANTATION; PULMONARY-HYPERTENSION; CONDITIONING REGIMEN; THALASSEMIA MAJOR; REDUCED-TOXICITY; EXPERT PANEL; ANEMIA; CHILDREN; ADULTS; SURVIVAL AB Although a number of published trials exist of HLA-identical sibling hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) that span 2 decades, when and for whom this therapy should be pursued is a subject of debate. Assessments of the risks of transplant-related complications that include infertility and debilitating graft-versus-host disease and long-term quality of life after successful HCT, are difficult to perform without prospective trials in transplant and nontransplant cohorts. However, it is possible to assess the risk of mortality and to compare published rates of survival in individuals with SCD treated and not treated by HCT. In this brief review, projections about mortality risk based on recent published reports are reviewed and summarized. The published data show overall survival and event-free survival rates of 95% and 92%, respectively, in children treated by HLA-identical sibling HCT. The overall survival rates in the Center for International Blood and Marrow Transplant Research (N = 412) and European Blood and Marrow Transplant (N = 487) registries were 91% and 95%, respectively. These results provide broad support for the therapeutic value of HLA-identical sibling HCT for children with SCD and serve as the basis for a strong recommendation in favor of the option of HCT when a suitable donor is available. The experience of HLA-identical sibling HCT in adults with SCD is limited but appears to be similar to results in childien. These preliminary observations, however, warrant further investigation. (C) 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. C1 [Walters, Mark C.] Univ Calif San Francisco, Benioff Childrens Hosp, Blood & Marrow Transplant Program, Oakland, CA 94609 USA. [De Castro, Laura M.] Univ Pittsburgh, Med Ctr, Div Hematol & Oncol, Pittsburgh, PA USA. [Sullivan, Keith M.] Duke Univ, Med Ctr, Blood & Marrow Transplant Program, Durham, NC USA. [Krishnamurti, Lakshmanan] Emory Univ, Dept Pediat, Aflac Canc & Blood Disorders Ctr, Atlanta, GA 30322 USA. [Kamani, Naynesh] AABB, Ctr Cellular Therapies & Res, Bethesda, MD USA. [Bredeson, Christopher] Univ Ottawa, Ottawa Hosp Res Inst, Blood & Marrow Transplant Program, Ottawa, ON, Canada. [Neuberg, Donna] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Hassell, Kathryn L.] Univ Colorado, Sch Med, Aurora, CO USA. [Farnia, Stephanie] Natl Marrow Donor Program, Minneapolis, MN USA. [Campbell, Andrew] Univ Michigan, Sch Med, Dept Pediat, Blood & Marrow Transplant Program,Div Pediat Hema, Ann Arbor, MI USA. [Petersdorf, Effie] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Petersdorf, Effie] Univ Washington, Sch Med, Seattle, WA USA. RP Walters, MC (reprint author), Univ Calif San Francisco, Benioff Childrens Hosp, 747 52nd St, Oakland, CA 94609 USA. EM mwalters@mail.cho.org FU NHLBI NIH HHS [R34 HL108761] NR 46 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2016 VL 22 IS 2 BP 207 EP 211 DI 10.1016/j.bbmt.2015.10.017 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DC2JD UT WOS:000369042100004 PM 26500093 ER PT J AU Pasquini, MC Zhang, MJ Medeiros, BC Armand, P Hui, ZH Nishihori, T Aljurf, MD Akpek, G Cahn, JY Cairo, MS Cerny, J Copelan, EA Deol, A Freytes, CO Gale, RP Ganguly, S George, B Gupta, V Hale, GA Kamble, RT Klumpp, TR Lazarus, HM Luger, SM Liesveld, JL Litzow, MR Marks, DI Martino, R Norkin, M Olsson, RF Oran, B Pawarode, A Pulsipher, MA Ramanathan, M Reshef, R Saad, AA Saber, W Savani, BN Schouten, HC Ringden, O Tallman, MS Uy, GL Wood, WA Wirk, B Perez, WS Batiwalla, M Weisdorf, DJ AF Pasquini, Marcelo C. Zhang, Mei-Jie Medeiros, Bruno C. Armand, Philippe Hui, Zhen-Huan Nishihori, Taiga Aljurf, Mahmoud D. Akpek, Goerguen Cahn, Jean-Yves Cairo, Mitchell S. Cerny, Jan Copelan, Edward A. Deol, Abhinav Freytes, Cesar O. Gale, Robert Peter Ganguly, Siddhartha George, Biju Gupta, Vikas Hale, Gregory A. Kamble, Rammurti T. Klumpp, Thomas R. Lazarus, Hillard M. Luger, Selina M. Liesveld, Jane L. Litzow, Mark R. Marks, David I. Martino, Rodrigo Norkin, Maxim Olsson, Richard F. Oran, Betul Pawarode, Attaphol Pulsipher, Michael A. Ramanathan, Muthalagu Reshef, Ran Saad, Ayman A. Saber, Wael Savani, Bipin N. Schouten, Harry C. Ringden, Olle Tallman, Martin S. Uy, Geoffrey L. Wood, William A., Jr. Wirk, Baldeep Perez, Waleska S. Batiwalla, Minoo Weisdorf, Daniel J. TI Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Monosomal karyotype; Acute myeloid leukemia; Myelodysplastic syndrome; Allogeneic transplantation ID ACUTE MYELOGENOUS LEUKEMIA; MYELODYSPLASTIC SYNDROMES; REDUCED-INTENSITY; PROGNOSTIC VALUE; SCORING SYSTEM; ALLOGENEIC TRANSPLANTATION; CYTOGENETIC ABNORMALITIES; MARROW-TRANSPLANTATION; CONDITIONING REGIMEN; INTERNATIONAL BLOOD AB The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+AML was associated with higher disease relapse (hazard ratio, 1.98; P < .01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P = .90), and worse survival (hazard ratio, 1.67; P < .01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P < .01), higher TRM (hazard ratio, 1.80; P < .01), and worse survival (HR, 2.02; P < .01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P < .01) and MDS (hazard ratio, 1.79; P < .01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Pasquini, Marcelo C.; Zhang, Mei-Jie; Hui, Zhen-Huan; Saber, Wael; Perez, Waleska S.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Zhang, Mei-Jie] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Medeiros, Bruno C.] Stanford Univ, Sch Med, Dept Hematol, Stanford, CA 94305 USA. [Armand, Philippe] Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA. [Nishihori, Taiga] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA. [Aljurf, Mahmoud D.] King Faisal Specialist Hosp & Res Ctr, Dept Oncol, Riyadh 11211, Saudi Arabia. [Akpek, Goerguen] Banner MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy Program, Gilbert, AZ USA. [Cahn, Jean-Yves] Univ Hosp, Dept Hematol, Grenoble, France. [Cairo, Mitchell S.] New York Med Coll, Dept Pediat, Div Pediat Hematol Oncol & Stem Cell Transplantat, Valhalla, NY 10595 USA. [Cerny, Jan; Ramanathan, Muthalagu] UMass Mem Med Ctr, Dept Med, Worcester, MA USA. [Copelan, Edward A.] Carolinas HealthCare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA. [Deol, Abhinav] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [Freytes, Cesar O.] S Texas Vet Hlth Care Syst, Div Hematol & Oncol, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Hematol Res Ctr, London, England. [Ganguly, Siddhartha] Univ Kansas, Med Ctr, Div Hematol & Oncol, Blood & Marrow Transplantat, Kansas City, KS 66103 USA. [George, Biju] Christian Med Coll & Hosp, Dept Haematol, Vellore, Tamil Nadu, India. [Gupta, Vikas] Univ Hlth Network, Princess Margaret Canc Ctr, Blood & Marrow Transplant Program, Toronto, ON, Canada. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, Dept Hematol Oncol, St Petersburg, FL 33701 USA. [Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Div Hematol & Oncol, Houston, TX 77030 USA. [Klumpp, Thomas R.] Thomas Jefferson Univ Hosp, Dept Med Oncol, Philadelphia, PA 19107 USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Luger, Selina M.; Reshef, Ran] Univ Penn, Med Ctr, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. [Liesveld, Jane L.] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA. [Litzow, Mark R.] Mayo Clin, Div Hematol & Transplant Ctr, Rochester, MN USA. [Marks, David I.] Univ Hosp Bristol NHS Trust, Pediat Bone Marrow Transplant, Bristol, Avon, England. [Martino, Rodrigo] Hosp Santa Creu & Sant Pau, Div Clin Hematol, Barcelona, Spain. [Norkin, Maxim] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL USA. [Olsson, Richard F.; Ringden, Olle] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden. [Olsson, Richard F.] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden. [Oran, Betul] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Div Canc Med, Houston, TX 77030 USA. [Pawarode, Attaphol] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Pulsipher, Michael A.] Univ So Calif, Keck Sch Med, Childrens Hosp Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA 90033 USA. [Saad, Ayman A.] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. [Savani, Bipin N.] Vanderbilt Univ, Dept Med, Div Hematol Oncol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Schouten, Harry C.] Acad Ziekenhuis, Dept Hematol, Maastricht, Netherlands. [Ringden, Olle] Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, 1275 York Ave, New York, NY 10021 USA. [Uy, Geoffrey L.] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Wood, William A., Jr.] Univ N Carolina, Dept Med, Div Hematol Oncol, Chapel Hill, NC USA. [Wirk, Baldeep] Seattle Canc Care Alliance, Div Bone Marrow Transplant, Seattle, WA USA. [Batiwalla, Minoo] NHLBI, NIH, Hematol Branch, Bldg 10, Bethesda, MD 20892 USA. [Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. RP Pasquini, MC (reprint author), 9200 W Wisconsin Ave, Milwaukee, WI 52336 USA. EM mpasquini@mcw.edu FU Public Health Service from the National Cancer Institute (NCI) [U24-CA076518]; Public Health Service from National Heart, Lung and Blood Institute (NHLBI) [U24-CA076518]; Public Health Service from National Institute of Allergy and Infectious Diseases (NIAID) [U24-CA076518]; NHLBI [5U10HL069294]; NCI [5U10HL069294]; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the United States Government. NR 44 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2016 VL 22 IS 2 BP 248 EP 257 DI 10.1016/j.bbmt.2015.08.024 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DC2JD UT WOS:000369042100010 PM 26327629 ER PT J AU Mawardi, H Glotzbecker, B Richardson, P Woo, SB AF Mawardi, Hani Glotzbecker, Brett Richardson, Paul Woo, Sook-Bin TI Hematopoietic Cell Transplantation in Patients with Medication-Related Osteonecrosis of the Jaws SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic cell transplantation; Osteonecrosis of the jaws ID BISPHOSPHONATE-INDUCED OSTEONECROSIS; BONE-MARROW-TRANSPLANTATION; BLOOD-STREAM INFECTION; HIGH-DOSE CHEMOTHERAPY; COUNCIL MYELOMA IX; MULTIPLE-MYELOMA; RECIPIENTS; COMPLICATIONS; THERAPY; BACTEREMIA AB Patients with medication-related osteonecrosis of the jaw (MRONJ) are at risk for developing infections and often require long-term antimicrobial therapy for management. It is unclear whether patients with multiple myeloma (MM) who develop MRONJ experience increased morbidity when they undergo hematopoietic cell transplantation (HCT). The aim of this study was to characterize the course of HCT in MM patients with MRONJ. A retrospective chart review was conducted for patients with MM and MRONJ who underwent HCT between December 2005 and December 2014. Data collected included bisphosphonate use, MRONJ stage, positive blood cultures, number of febrile days, and length of hospital stay. Eleven patients (median age, 61; range, 46 to 71) fulfilled the criteria. Patients received zoledronic acid (72.7%), pamidronate (18.1%), or a combination of both (9%). At the time of HCT, 10 patients were in stage 1 MRONJ with 1 in stage 0. All patients had only mandibular involvement. No patient developed pain/infection at the MRONJ site during hospitalization. Bacteremia with positive blood cultures for Staphylococcus aureus occurred in 3 patients (27.2%), and 4 patients (36.3%) developed fever lasting between 4 to 6 days (of who 1 had positive blood cultures). The median length of hospital stay was 17 days (range, 7 to 22 days). These data suggests that patients with MM and MRONJ who undergo HCT are not at increased risk of developing symptoms associated with the MRONJ site or HCT-related infectious complications, and their MRONJ is not worsened by HCT. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Mawardi, Hani; Woo, Sook-Bin] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. [Mawardi, Hani; Woo, Sook-Bin] Brigham & Womens Hosp, Dept Surg, Div Oral Med & Dent, 75 Francis St, Boston, MA 02115 USA. [Mawardi, Hani] King Abdulaziz Univ, Fac Dent, Dept Oral Med, Jeddah 21413, Saudi Arabia. [Glotzbecker, Brett] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Glotzbecker, Brett] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Richardson, Paul] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Richardson, Paul] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. RP Mawardi, H (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 75 Francis St, Boston, MA 02115 USA. EM hmawardi@gmail.com NR 40 TC 0 Z9 0 U1 17 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2016 VL 22 IS 2 BP 344 EP 348 DI 10.1016/j.bbmt.2015.08.021 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DC2JD UT WOS:000369042100022 PM 26303103 ER PT J AU Young, JAH Logan, BR Wu, J Wingard, JR Weisdorf, DJ Mudrick, C Knust, K Horowitz, MM Confer, DL Dubberke, ER Pergam, SA Marty, FM Strasfeld, LM Brown, JM Langston, AA Schuster, MG Kaul, DR Martin, SI Anasetti, C AF Young, Jo-Anne H. Logan, Brent R. Wu, Juan Wingard, John R. Weisdorf, Daniel J. Mudrick, Cathryn Knust, Kristin Horowitz, Mary M. Confer, Dennis L. Dubberke, Erik R. Pergam, Steven A. Marty, Francisco M. Strasfeld, Lynne M. Brown, Janice (Wes) M. Langston, Amelia A. Schuster, Mindy G. Kaul, Daniel R. Martin, Stanley I. Anasetti, Claudio CA Blood Marrow Transplant Clinical T TI Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Infection; Unrelated donor transplantation; Bacteremia; Cytomegalovirus; Aspergillosis; Pre-engraftment ID VERSUS-HOST-DISEASE; ALLOGENEIC TRANSPLANTATION; ASPERGILLUS INFECTIONS; CORD BLOOD; CYTOMEGALOVIRUS; RECIPIENTS; IMPACT; COMPLICATIONS; MALIGNANCIES; DEPLETION AB Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P = .027). The total infection density (number of infection events/100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections, it was .2 in both arms; and for fungal parasitic infections, it was .04 and .05 for BM and PBSC, respectively. The cumulative incidence of infection before engraftment was 47.9% (95% CI, 41.5 to 53.9) for BM versus 32.8% (95% CI, 27.1 to 38.7) for PBSC (P = .002), possibly related to quicker neutrophil engraftment using PBSC. Infections remain frequent after unrelated donor hematopoietic cell transplantation, particularly after BM grafts. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Young, Jo-Anne H.; Weisdorf, Daniel J.] Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA. [Logan, Brent R.; Horowitz, Mary M.] Med Coll Wisconsin, MMH Dept Med, Div Biostat, BRL Inst Hlth & Soc, Milwaukee, WI 53226 USA. [Wu, Juan; Mudrick, Cathryn; Knust, Kristin] EMMES Corp, Blood & Bone Marrow Transplant Clin Trials Networ, Rockville, MD USA. [Wingard, John R.] Univ Florida, Dept Med, Shands Canc Ctr, Gainesville, FL USA. [Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA. [Dubberke, Erik R.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Pergam, Steven A.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA. [Marty, Francisco M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Strasfeld, Lynne M.] Oregon Hlth & Sci Univ, Dept Med, Div Infect Dis, Portland, OR 97201 USA. [Brown, Janice (Wes) M.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. [Langston, Amelia A.] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Schuster, Mindy G.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Kaul, Daniel R.] Univ Michigan, Dept Internal Med, Div Infect Dis, Ann Arbor, MI 48109 USA. [Martin, Stanley I.] Ohio State Univ, Dept Internal Med, Div Infect Dis, Columbus, OH 43210 USA. [Anasetti, Claudio] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA. RP Young, JAH (reprint author), Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA. EM vanbu004@umn.edu FU National Heart, Lung, and Blood Institute; National Cancer Institute [U10HL069294]; Office of Naval Research; National Marrow Donor Program FX This study was supported by a grant from the National Heart, Lung, and Blood Institute and the National Cancer Institute (U10HL069294), by the Office of Naval Research, and by the National Marrow Donor Program. Disclosure forms were provided by the authors. The authors thank the transplantation center teams in the United States and Canada for enrolling patients in this trial; the donor-center teams in the United States, Canada, and Germany for recruiting the donors for the trial; and the National Marrow Donor Program coordinating center for facilitating the transplantations. NR 27 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2016 VL 22 IS 2 BP 359 EP 370 DI 10.1016/j.bbmt.2015.09.013 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DC2JD UT WOS:000369042100024 PM 26409243 ER PT J AU Cowan, AJ Stevenson, PA Cassaday, RD Graf, SA Fromm, JR Wu, D Holmberg, LA Till, BG Chauncey, TR Smith, SD Philip, M Orozco, JJ Shustov, AR Green, DJ Libby, EN Bensinger, WI Shadman, M Maloney, DG Press, OW Gopal, AK AF Cowan, Andrew J. Stevenson, Philip A. Cassaday, Ryan D. Graf, Solomon A. Fromm, Jonathan R. Wu, David Holmberg, Leona A. Till, Brian G. Chauncey, Thomas R. Smith, Stephen D. Philip, Mary Orozco, Johnnie J. Shustov, Andrei R. Green, Damian J. Libby, Edward N., III Bensinger, William I. Shadman, Mazyar Maloney, David G. Press, Oliver W. Gopal, Ajay K. TI Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Mantle cell lymphoma; Transplantation; Minimal residual disease; Predictors; Survival ID INTERNATIONAL PROGNOSTIC INDEX; PROGRESSION-FREE SURVIVAL; NON-HODGKINS-LYMPHOMA; HIGH-DOSE THERAPY; FLOW-CYTOMETRY; MOLECULAR REMISSION; RESPONSE ASSESSMENT; IMMUNOCHEMOTHERAPY; TOMOGRAPHY; CLASSIFICATION AB Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission after induction chemotherapy, with the best results for patients in complete remission (CR). We hypothesized that evaluation of minimal residual disease (MRD) before ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011 with pretransplantation MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11; 14) by PCR or positive flow cytometry from blood or bone marrow, was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached, with 82% survival at 5 years, whereas for the MRD-positive patients, median OS was 3.01 years (hazard ratio [HR], 4.04; P = .009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75% PFS at 5 years, whereas for MRD-positive patients, it was 238 years (HR, 3.69; P = .002). MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Cowan, Andrew J.; Stevenson, Philip A.; Cassaday, Ryan D.; Graf, Solomon A.; Holmberg, Leona A.; Till, Brian G.; Chauncey, Thomas R.; Smith, Stephen D.; Philip, Mary; Orozco, Johnnie J.; Shustov, Andrei R.; Green, Damian J.; Bensinger, William I.; Shadman, Mazyar; Press, Oliver W.; Gopal, Ajay K.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA. [Fromm, Jonathan R.; Wu, David] Univ Washington, Dept Lab Med, Marrow Transplant Unit, Seattle, WA 98195 USA. [Chauncey, Thomas R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Libby, Edward N., III] Univ Washington, Dept Med, Div Med Oncol, Seattle, WA USA. [Maloney, David G.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Transplantat Biol Dept, 1124 Columbia St, Seattle, WA 98104 USA. RP Gopal, AK (reprint author), 825 Eastlake Ave E,MS G3-200, Seattle, WA 98109 USA. EM agopal@u.washington.edu FU NIH [P01CA044991, K24CA184039]; Lymphoma Research Foundation Mantle Cell Lymphoma Research Initiative Clinical Scholar Award by the Leukemia and Lymphoma Society; Mary Aileen Wright Memorial Fund; David and Patricia Giuliani Family Foundation; [5T32 CA009515-30] FX A.J.C. is supported by 5T32 CA009515-30. This work was supported by research funding from NIH P01CA044991 and K24CA184039; Lymphoma Research Foundation Mantle Cell Lymphoma Research Initiative Clinical Scholar Award by the Leukemia and Lymphoma Society, to A.K.G.; the Mary Aileen Wright Memorial Fund; the David and Patricia Giuliani Family Foundation; and philanthropic gifts from Frank and Betty Vandermeer and Don and Debbie Hunkins. NR 34 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2016 VL 22 IS 2 BP 380 EP 385 DI 10.1016/j.bbmt.2015.08.035 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DC2JD UT WOS:000369042100027 PM 26348890 ER PT J AU Park, J Cheng, JT Ferguson, D Maguluri, G Chang, EW Clancy, C Lee, DJ Iftimia, N AF Park, Jesung Cheng, Jeffrey T. Ferguson, Daniel Maguluri, Gopi Chang, Ernest W. Clancy, Caitlin Lee, Daniel J. Iftimia, Nicusor TI Investigation of middle ear anatomy and function with combined video otoscopy-phase sensitive OCT SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; TYMPANIC MEMBRANE; MOUSE COCHLEA; HEARING-LOSS; LASER; AUDIOMETRY; VIBROMETRY; SURFACE AB We report the development of a novel otoscopy probe for assessing middle ear anatomy and function. Video imaging and phase-sensitive optical coherence tomography are combined within the same optical path. A sound stimuli channel is incorporated as well to study middle ear function. Thus, besides visualizing the morphology of the middle ear, the vibration amplitude and frequency of the eardrum and ossicles are retrieved as well. Preliminary testing on cadaveric human temporal bone models has demonstrated the capability of this instrument for retrieving middle ear anatomy with micron scale resolution, as well as the vibration of the tympanic membrane and ossicles with sub-nm resolution. (C) 2016 Optical Society of America C1 [Park, Jesung; Ferguson, Daniel; Maguluri, Gopi; Chang, Ernest W.; Clancy, Caitlin; Iftimia, Nicusor] Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. [Cheng, Jeffrey T.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. RP Iftimia, N (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. EM iftimia@psicorp.com FU National Institute on Deafness and Other Communication Disorders (NIDCD) [1R43DC013923] FX This work was supported by a grant from the National Institute on Deafness and Other Communication Disorders (NIDCD): 1R43DC013923. NR 29 TC 2 Z9 2 U1 3 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD FEB 1 PY 2016 VL 7 IS 2 BP 238 EP 250 DI 10.1364/BOE.7.000238 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA DC5FN UT WOS:000369247000001 PM 26977336 ER PT J AU Haindl, R Trasischker, W Wartak, A Baumann, B Pircher, M Hitzenberger, CK AF Haindl, Richard Trasischker, Wolfgang Wartak, Andreas Baumann, Bernhard Pircher, Michael Hitzenberger, Christoph K. TI Total retinal blood flow measurement by three beam Doppler optical coherence tomography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID DUAL-ANGLE; HUMAN EYE; VELOCITY; OCT; RESOLUTION; GLAUCOMA; VESSELS; MIRROR; LIGHT AB We present measurements of total retinal blood flow in healthy volunteers using a three beam Doppler optical coherence tomography (DOCT) technique. This technology has the advantage of a precise determination of the flow vector without the use of any a-priori information on the vessel geometry. Circular D-OCT scans around the optic disc were recorded and venous as well as arterial total blood flow was determined and compared for each subject. The reproducibility of the method was assessed in 6 subjects by repeated measurements. Only small deviations of around 6% between the measurements were found which indicates the high precision of the proposed method. (C) 2016 Optical Society of America C1 [Haindl, Richard; Trasischker, Wolfgang; Wartak, Andreas; Baumann, Bernhard; Pircher, Michael; Hitzenberger, Christoph K.] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria. [Trasischker, Wolfgang] Harvard Univ, Sch Med, Boston, MA USA. [Trasischker, Wolfgang] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Haindl, R; Hitzenberger, CK (reprint author), Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria. EM richard.haindl@meduniwien.ac.at; christoph.hitzenberger@meduniwien.ac.at OI Baumann, Bernhard/0000-0001-6419-1932 FU Austrian Science Fund [P26553-N20]; Medical Imaging Cluster at the Medical University of Vienna FX This work was supported by the Austrian Science Fund [grant number P26553-N20]. We are grateful to Magdalena Baratsits and Philipp Ken Roberts, MD, Department of Ophthalmology, Medical University of Vienna, for providing color fundus photos. Furthermore we want to thank the Medical Imaging Cluster at the Medical University of Vienna for their support. NR 45 TC 9 Z9 9 U1 3 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD FEB 1 PY 2016 VL 7 IS 2 BP 287 EP 301 DI 10.1364/BOE.7.000287 PG 15 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA DC5FN UT WOS:000369247000005 PM 26977340 ER PT J AU Ughi, GJ Gora, MJ Swager, AF Soomro, A Grant, C Tiernan, A Rosenberg, M Sauk, JS Nishioka, NS Tearney, GJ AF Ughi, Giovanni J. Gora, Michalina J. Swager, Anne-Fre Soomro, Amna Grant, Catriona Tiernan, Aubrey Rosenberg, Mireille Sauk, Jenny S. Nishioka, Norman S. Tearney, Guillermo J. TI Automated segmentation and characterization of esophageal wall in vivo by tethered capsule optical coherence tomography endomicroscopy SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID VOLUMETRIC LASER ENDOMICROSCOPY; BARRETTS-ESOPHAGUS; GASTROINTESTINAL-TRACT; CLASSIFICATION; ATTENUATION; ENDOSCOPY; IMAGES; TISSUE AB Optical coherence tomography (OCT) is an optical diagnostic modality that can acquire cross-sectional images of the microscopic structure of the esophagus, including Barrett's esophagus (BE) and associated dysplasia. We developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires high-resolution images of entire gastrointestinal (GI) tract luminal organs. This device has a potential to become a screening method that identifies patients with an abnormal esophagus that should be further referred for upper endoscopy. Currently, the characterization of the OCT-TCE esophageal wall data set is performed manually, which is time-consuming and inefficient. Additionally, since the capsule optics optimally focus light approximately 500 mu m outside the capsule wall and the best quality images are obtained when the tissue is in full contact with the capsule, it is crucial to provide feedback for the operator about tissue contact during the imaging procedure. In this study, we developed a fully automated algorithm for the segmentation of in vivo OCT-TCE data sets and characterization of the esophageal wall. The algorithm provides a two-dimensional representation of both the contact map from the data collected in human clinical studies as well as a tissue map depicting areas of BE with or without dysplasia. Results suggest that these techniques can potentially improve the current TCE data acquisition procedure and provide an efficient characterization of the diseased esophageal wall. (C) 2016 Optical Society of America C1 [Ughi, Giovanni J.; Gora, Michalina J.; Swager, Anne-Fre; Soomro, Amna; Grant, Catriona; Tiernan, Aubrey; Rosenberg, Mireille; Nishioka, Norman S.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Ughi, Giovanni J.; Gora, Michalina J.; Nishioka, Norman S.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA USA. [Gora, Michalina J.; Sauk, Jenny S.] Strasbourg Univ, CNRS, ICube, Strasbourg, France. [Nishioka, Norman S.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tearney, Guillermo J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Tearney, GJ (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Tearney, GJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Tearney, GJ (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM gtearney@partners.org OI Ughi, Giovanni J./0000-0003-3354-0698 FU US National Institutes of Health [NIH R01CA103769] FX This work was supported in part by US National Institutes of Health grant NIH R01CA103769 (GJT). NR 21 TC 8 Z9 8 U1 4 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD FEB 1 PY 2016 VL 7 IS 2 BP 409 EP 419 DI 10.1364/BOE.7.000409 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA DC5FN UT WOS:000369247000015 PM 26977350 ER PT J AU Velasquez, GE Cegielski, JP Murray, MB Yagui, MJA Asencios, LL Bayona, JN Bonilla, CA Jave, HO Yale, G Suarez, CZ Sanchez, E Rojas, C Atwood, SS Contreras, CC Cruz, JS Shin, SS AF Velasquez, Gustavo E. Cegielski, J. Peter Murray, Megan B. Yagui, Martin J. A. Asencios, Luis L. Bayona, Jaime N. Bonilla, Cesar A. Jave, Hector O. Yale, Gloria Suarez, Carmen Z. Sanchez, Eduardo Rojas, Christian Atwood, Sidney S. Contreras, Carmen C. Cruz, Janeth Santa Shin, Sonya S. TI Impact of HIV on mortality among patients treated for tuberculosis in Lima, Peru: a prospective cohort study SO BMC INFECTIOUS DISEASES LA English DT Article DE Tuberculosis; Human immunodeficiency virus; Clinical outcomes; Mortality; Prospective cohort study; Operational research ID MULTIDRUG-RESISTANT TUBERCULOSIS; ANTIRETROVIRAL THERAPY; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; INFECTED ADULTS; RISK-FACTORS; OUTCOMES; PROGRAM; IMPLEMENTATION; PREDICTORS AB Background: Human immunodeficiency virus (HIV)-associated tuberculosis deaths have decreased worldwide over the past decade. We sought to evaluate the effect of HIV status on tuberculosis mortality among patients undergoing treatment for tuberculosis in Lima, Peru, a low HIV prevalence setting. Methods: We conducted a prospective cohort study of patients treated for tuberculosis between 2005 and 2008 in two adjacent health regions in Lima, Peru (Lima Ciudad and Lima Este). We constructed a multivariate Cox proportional hazards model to evaluate the effect of HIV status on mortality during tuberculosis treatment. Results: Of 1701 participants treated for tuberculosis, 136 (8.0 %) died during tuberculosis treatment. HIV-positive patients constituted 11.0 % of the cohort and contributed to 34.6 % of all deaths. HIV-positive patients were significantly more likely to die (25.1 vs. 5.9 %, P < 0.001) and less likely to be cured (28.3 vs. 39.4 %, P = 0.003). On multivariate analysis, positive HIV status (hazard ratio [HR] = 6.06; 95 % confidence interval [CI], 3.96-9.27), unemployment (HR = 2.24; 95 % CI, 1.55-3.25), and sputum acid-fast bacilli smear positivity (HR = 1.91; 95 % CI, 1.10-3.31) were significantly associated with a higher hazard of death. Conclusions: We demonstrate that positive HIV status was a strong predictor of mortality among patients treated for tuberculosis in the early years after Peru started providing free antiretroviral therapy. As HIV diagnosis and antiretroviral therapy provision are more widely implemented for tuberculosis patients in Peru, future operational research should document the changing profile of HIV-associated tuberculosis mortality. C1 [Velasquez, Gustavo E.; Shin, Sonya S.] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Velasquez, Gustavo E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Velasquez, Gustavo E.; Shin, Sonya S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Cegielski, J. Peter] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. [Murray, Megan B.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Murray, Megan B.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Murray, Megan B.; Atwood, Sidney S.; Shin, Sonya S.] Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA. [Yagui, Martin J. A.] Inst Nacl Salud, Oficina Gen Invest & Transferencia Tecnol, Lima, Peru. [Yagui, Martin J. A.] Univ Nacl Mayor San Marcos, Dept Acad Med Prevent & Salud Publ, Lima 14, Peru. [Asencios, Luis L.] Inst Nacl Salud, Lab Nacl Referencia Micobacterias, Lima, Peru. [Bayona, Jaime N.] World Bank Grp, Hlth Nutr & Populat, Washington, DC USA. [Bonilla, Cesar A.; Jave, Hector O.] Minist Salud Peru, Estrategia Sanitaria Nacl Prevenc & Control TB, Lima, Peru. [Yale, Gloria] Direcc Salud V Lima Ciudad, Programa Control TB, Lima, Peru. [Suarez, Carmen Z.] Direcc Salud IV Lima Este, Programa Control TB, Lima, Peru. [Sanchez, Eduardo] Hosp Nacl Hipolito Unanue, Serv Enfermedades Infecciosas & Trop, Lima, Peru. [Rojas, Christian] Inst Nacl Cardiovasc Carlos Alberto Peschiera Car, Serv Neumol, Lima, Peru. [Contreras, Carmen C.; Cruz, Janeth Santa; Shin, Sonya S.] Partners Hlth Socios Salud, Lima, Peru. RP Velasquez, GE (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.; Velasquez, GE (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM gvelasquez@bwh.harvard.edu OI Velasquez, Gustavo/0000-0003-1438-0692 FU Bill and Melinda Gates Foundation; U.S. Centers for Disease Control and Prevention; National Institute of Allergy and Infectious Diseases at the National Institutes of Health [K23 AI054591, T32 AI007433]; Infectious Diseases Society of America; Heiser Foundation; Division of Global Health Equity at Brigham and Women's Hospital FX This publication was supported by the Bill and Melinda Gates Foundation; the U.S. Centers for Disease Control and Prevention; the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (grant numbers K23 AI054591 to SSS and T32 AI007433 to GEV); the Infectious Diseases Society of America; and the Heiser Foundation. GEV received support for publication costs from the Division of Global Health Equity at Brigham and Women's Hospital. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. Centers for Disease Control and Prevention, the National Institutes of Health, or the institutions with which the authors are affiliated. The funding sources played no role in the design, collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. NR 34 TC 0 Z9 0 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD FEB 1 PY 2016 VL 16 AR 45 DI 10.1186/s12879-016-1375-8 PG 11 WC Infectious Diseases SC Infectious Diseases GA DC6YA UT WOS:000369364300001 PM 26831140 ER PT J AU Gaffney, AW Hang, JQ Lee, MS Su, L Zhang, FY Christiani, DC AF Gaffney, Adam W. Hang, Jing-Qing Lee, Mi-Sun Su, Li Zhang, Feng-Ying Christiani, David C. TI Socioeconomic status is associated with reduced lung function in China: an analysis from a large cross-sectional study in Shanghai SO BMC PUBLIC HEALTH LA English DT Article DE Socioeconomic factors; Respiratory disease; Environmental health; Epidemiology; China; Pulmonary function ID RECOMBINANT HUMAN DEOXYRIBONUCLEASE; PARENTAL STRESS INCREASES; SOLID-FUEL USE; PULMONARY-FUNCTION; AIR-POLLUTION; TRANSPORT MICROENVIRONMENTS; RESPIRATORY HEALTH; EDUCATIONAL-LEVEL; CYSTIC-FIBROSIS; SOCIAL-CLASS AB Background: An inverse association between socioeconomic status and pulmonary function has emerged in many studies. However, the mediating factors in this relationship are poorly understood, and might be expected to differ between countries. We sought to investigate the relationship between socioeconomic status and lung function in China, a rapidly industrializing nation with unique environmental challenges, and to identify potentially-modifiable environmental mediators. Methods: We used data from the Shanghai Putuo Study, a cross-sectional study performed in Shanghai, China. Participants completed a questionnaire and spirometry. The primary exposure was socioeconomic status, determined by education level. The primary outcomes were FEV1 and FVC percent predicted. Multiple linear regressions were used to test this association, and the percent explained by behavioral, environmental, occupational, and dietary variables was determined by adding these variables to a base model. Results: The study population consisted of a total of 22,878 study subjects that were 53.3 % female and had a mean age of 48. In the final multivariate analysis, the effect estimates for FEV1 and FVC percent predicted for low socioeconomic status (compared to high) were statistically significant at a p-value of <0.01. Smoking, biomass exposure, mode of transportation to work, a diet low in fruits or vegetables, and occupational category partially attenuated the relationship between SES and lung function. In a fully-adjusted age-stratified analysis, the socioeconomic disparity in lung function widened with increasing age. Conclusions: We found cross-sectional evidence of socioeconomic disparities in pulmonary function in Shanghai. These differences increased with age and were partially explained by potentially modifiable exposures. C1 [Gaffney, Adam W.; Christiani, David C.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Hang, Jing-Qing; Zhang, Feng-Ying] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Lee, Mi-Sun; Su, Li; Christiani, David C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, 677 Huntington Ave, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gaffney, AW (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM agaffney@mgh.harvard.edu FU National Institutes of Health Shanghai Putuo District People's Hospital [T32 HL116275, ES000002] FX National Institutes of Health (T32 HL116275 and ES000002) Shanghai Putuo District People's Hospital NR 40 TC 1 Z9 1 U1 3 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD FEB 1 PY 2016 VL 16 AR 96 DI 10.1186/s12889-016-2752-3 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DC8PF UT WOS:000369480900001 PM 26832923 ER PT J AU Prebet, T Sun, ZX Ketterling, RP Zeidan, A Greenberg, P Herman, J Juckett, M Smith, MR Malick, L Paietta, E Czader, M Figueroa, M Gabrilove, J Erba, HP Tallman, MS Litzow, M Gore, SD AF Prebet, Thomas Sun, Zhuoxin Ketterling, Rhett P. Zeidan, Amer Greenberg, Peter Herman, James Juckett, Mark Smith, Mitchell R. Malick, Lisa Paietta, Elisabeth Czader, Magdalena Figueroa, Maria Gabrilove, Janice Erba, Harry P. Tallman, Martin S. Litzow, Mark Gore, Steven D. CA Eastern Cooperative Oncology Grp North Amer Leukemia Intergrp TI Azacitidine with or without Entinostat for the treatment of therapy-related myeloid neoplasm: further results of the E1905 North American Leukemia Intergroup study SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myelodysplasia; acute myeloid leukaemia; azacitidine; histone deacetylase inhibitor; therapy related ID CONVENTIONAL CARE REGIMENS; LOW-DOSE DECITABINE; MYELODYSPLASTIC SYNDROMES; SCORING SYSTEM; ADULTS; CANCER; TRIAL AB Therapy-related myeloid neoplasms (tMN) are serious late effects of the treatment of cancer with poor response to conventional treatment. Azacitidine (AZA) has been used to treat patients with tMN but current data are retrospective. We present here 47 tMN patients prospectively enrolled as a specific cohort in the E1905 study. TheE1905 study was a randomized phase 2 study (NCT00313586) testing 10 d of AZA (50 mg/m(2)/d) +/- the histone deacetylase inhibitor entinostat (4 mg/m(2)/d PO day-3 and day-10). A total of 47 patients [29 therapy-related myelosyspastic syndrome (t-MDS) and 18 therapy-related acute myeloid leukaemia (t-AML)] were recruited to the study. 24 patients were treated with AZA monotherapy and 23 with AZA+ entinostat. The median number of administered cycles was 4, significantly higher in patients treated with AZA (6 cycles vs. 3 cycles, P = 0.008). Haematological normalization rates were 46% in monotherapy and 17% in the combination arm. Median overall survivals were 13 and 6 months, respectively. The novel 50 * 10 schedule of azacitidine appears effective, with response rates, when given as single agent, comparable to those for patients with de novo MDS/AML treated on the same protocol. However, the combination of AZA and entinostat was associated with increased toxicity and could not be recommended for treatment of tMN. C1 [Prebet, Thomas; Zeidan, Amer; Gore, Steven D.] Yale Canc Ctr, Sect Hematol, 300 George St,7th Floor,RM 786, New Haven, CT 06511 USA. [Sun, Zhuoxin] Dana Farber Canc Inst, ECOG ACRIN Biostat Ctr, Boston, MA 02115 USA. [Ketterling, Rhett P.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Greenberg, Peter] Stanford Univ, Ctr Canc, Div Hematol, Stanford, CA 94305 USA. [Herman, James; Malick, Lisa] Johns Hopkins Univ, Baltimore, MD USA. [Juckett, Mark] Univ Wisconsin, Madison, WI USA. [Smith, Mitchell R.] Cleveland Clin, Cleveland, OH 44106 USA. [Paietta, Elisabeth] Montefiore Med Ctr, North Div, 111 E 210th St, Bronx, NY 10467 USA. [Czader, Magdalena] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. [Figueroa, Maria] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Gabrilove, Janice] Icahn Sch Med Mt Sinai, Sch Med, Tisch Canc Inst, New York, NY 10029 USA. [Erba, Harry P.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Tallman, Martin S.] Mem Sloane Kettering Canc Ctr, Leukemia Serv, New York, NY USA. [Litzow, Mark] Mayo Clin, Coll Med, Ctr Canc, Div Hematol, Rochester, MN USA. RP Prebet, T (reprint author), Yale Canc Ctr, Sect Hematol, 300 George St,7th Floor,RM 786, New Haven, CT 06511 USA. EM Thomas.prebet@yale.edu OI Prebet, Thomas/0000-0002-6872-625X FU Leukemia and Lymphoma Society of America [R01 CA125563501, R6034-08]; Fulbright Franco-American commission/Foundation Monahan, Paris, France [CA32102, CA27057]; [K24 CA111717] FX Supported by R01 CA125563501 (SG), R6034-08 from the Leukemia and Lymphoma Society of America (SG), K24 CA111717 (SG) and a grant from the Fulbright Franco-American commission/Foundation Monahan, Paris, France (TP). CA32102 and CA27057 (HPE). NR 24 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2016 VL 172 IS 3 BP 384 EP 391 DI 10.1111/bjh.13832 PG 8 WC Hematology SC Hematology GA DC5WA UT WOS:000369290100006 PM 26577691 ER PT J AU Ye, SA Zhang, JM Shen, J Gao, Y Li, Y Choy, E Cote, G Harmon, D Mankin, H Gray, NS Hornicek, FJ Duan, ZF AF Ye, Shunan Zhang, Jianming Shen, Jacson Gao, Yan Li, Ying Choy, Edwin Cote, Gregory Harmon, David Mankin, Henry Gray, Nathanael S. Hornicek, Francis J. Duan, Zhenfeng TI NVP-TAE684 reverses multidrug resistance (MDR) in human osteosarcoma by inhibiting P-glycoprotein (PGP1) function SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article ID TYROSINE KINASE INHIBITOR; DRUG-RESISTANCE; OVARIAN-CANCER; CELL-LINES; CONCISE GUIDE; SOLID TUMORS; LUNG-CANCER; MECHANISMS; POTENT; CHEMOTHERAPY AB Background and purposeIncreased expression of P-glycoprotein (PGP1) is one of the major causes of multidrug resistance (MDR) in cancer, including in osteosarcoma, which eventually leads to the failure of cancer chemotherapy. Thus, there is an urgent need to develop effective therapeutic strategies to override the expression and function of PGP1 to counter MDR in cancer patients. Experimental ApproachIn an effort to search for new chemical entities targeting PGP1-associated MDR in osteosarcoma, we screened a 500+ compound library of known kinase inhibitors with established kinase selectivity profiles. We aimed to discover potential drug synergistic effects among kinase inhibitors and general chemotherapeutics by combining inhibitors with chemotherapy drugs such as doxorubicin and paclitaxel. The human osteosarcoma MDR cell lines U2OSR2 and KHOSR2 were used for the initial screen and secondary mechanistic studies. Key ResultsAfter screening 500+ kinase inhibitors, we identified NVP-TAE684 as the most effective MDR reversing agent. NVP-TAE684 significantly reversed chemoresistance when used in combination with doxorubicin, paclitaxel, docetaxel, vincristine, ET-743 or mitoxantrone. NVP-TAE684 itself is not a PGP1 substrate competitive inhibitor, but it can increase the intracellular accumulation of PGP1 substrates in PGP1-overexpressing cell lines. NVP-TAE684 was found to inhibit the function of PGP1 by stimulating PGP1 ATPase activity, a phenomenon reported for other PGP1 inhibitors. Conclusions and ImplicationsThe application of NVP-TAE684 to restore sensitivity of osteosarcoma MDR cells to the cytotoxic effects of chemotherapeutics will be useful for further study of PGP1-mediated MDR in human cancer and may ultimately benefit cancer patients. C1 [Ye, Shunan; Shen, Jacson; Gao, Yan; Choy, Edwin; Cote, Gregory; Harmon, David; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Sarcoma & Connect Tissue Oncol, 100 Blossom St,Jackson 1115, Boston, MA 02114 USA. [Zhang, Jianming; Li, Ying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA USA. [Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RP Duan, ZF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Sarcoma & Connect Tissue Oncol, 100 Blossom St,Jackson 1115, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu OI Cote, Gregory/0000-0003-0181-886X FU Gategno fund; Wechsler fund; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [UO1, CA 151452]; Jennifer Hunter Yates Foundation; Kenneth Stanton Fund FX This study was supported, in part, by grants from the Gategno and Wechsler funds. Z.D. is supported, in part, through a grant from Sarcoma Foundation of America (SFA) and a grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA 151452. Support was also provided by the Jennifer Hunter Yates Foundation and the Kenneth Stanton Fund. NR 50 TC 3 Z9 3 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 EI 1476-5381 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD FEB PY 2016 VL 173 IS 3 BP 613 EP 626 DI 10.1111/bph.13395 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DC3WM UT WOS:000369149600016 PM 26603906 ER PT J AU Yin, PQ Hong, Z Yang, XJ Chung, RT Zhang, LL AF Yin, Peiqi Hong, Zhi Yang, Xiaojie Chung, Raymond T. Zhang, Leiliang TI A role for retromer in hepatitis C virus replication SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE HCV; NS5A; PI4P; Retromer; CIMPR ID OXYSTEROL-BINDING-PROTEIN; CELLULAR COFACTORS; CARGO; COMPLEX; RECEPTOR; TIP47; NS5A; TRAFFICKING; RECRUITMENT; PARTICLES AB Hepatitis C virus (HCV) has infected over 170 million people worldwide. Phosphatidylinositol 4-phosphate (PI4P) is the organelle-specific phosphoinositide enriched at sites of HCV replication. Whether retromer, a PI4P-related host transport machinery, unloads its cargo at HCV replication sites remains inconclusive. We sought to characterize the role of retromer in HCV replication. Here, we demonstrated the interaction between retromer subunit Vps35 and HCV NS5A protein by immunoprecipitation and GST pulldown. Vps35 colocalized with NS5A and PI4P in both OR6 replicon and JFH1 infected Huh 7.5.1 cells. HCV replication was inhibited upon silencing retromer subunits. CIMPR, a typical retromer cargo, participated in HCV replication. Our data suggest that retromer component Vps35 is recruited by NS5A to viral replication sites where PI4P unloads CIMPR. These findings demonstrate a dependence role of retromer in HCV replication and identify retromer as a potential therapeutic target against HCV. C1 [Yin, Peiqi; Hong, Zhi; Yang, Xiaojie; Zhang, Leiliang] Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100176, Peoples R China. [Yin, Peiqi; Hong, Zhi; Yang, Xiaojie; Zhang, Leiliang] Peking Union Med Coll, Beijing 100176, Peoples R China. [Chung, Raymond T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Div,Dept Med,Liver Ctr, Boston, MA 02114 USA. RP Zhang, LL (reprint author), Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100176, Peoples R China.; Zhang, LL (reprint author), Peking Union Med Coll, Beijing 100176, Peoples R China. EM armzhang@hotmail.com FU National Natural Science Foundation of China [81301438, 81271832, 81471955]; National Science and Technology Major Project of China [2013ZX10004-601]; Intramural Research Program of the Institute of Pathogen Biology, CAMS [2013IPB104]; Program for Changjiang Scholars and Innovative Research Team in University [IRT13007]; PUMC Youth Fund, the Fundamental Research Funds for the Central Universities [3332013118]; NIH [DK098079, AI082630, DA033541] FX This work was supported by Grants from National Natural Science Foundation of China (81301438, 81271832, 81471955), National Science and Technology Major Project of China (2013ZX10004-601), Intramural Research Program of the Institute of Pathogen Biology, CAMS (2013IPB104), Program for Changjiang Scholars and Innovative Research Team in University (IRT13007), PUMC Youth Fund, the Fundamental Research Funds for the Central Universities (3332013118), and NIH (DK098079, AI082630, and DA033541). We thank Guangbo Yang for technical support. We thank Jing Wang for critical review of the manuscript. We thank Charles Rice, Francis Chisari, Masanori Ikeda, Nobuyuki Kato and Takaji Wakita for reagents. NR 45 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X EI 1420-9071 J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD FEB PY 2016 VL 73 IS 4 BP 869 EP 881 DI 10.1007/s00018-015-2027-7 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DC9IQ UT WOS:000369535300012 PM 26298293 ER PT J AU Babic, A Wolpin, BM AF Babic, Ana Wolpin, Brian M. TI Circulating Exosomes in Pancreatic Cancer: Will They Succeed on the Long, Littered Road to Early Detection Marker? SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Babic, Ana; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Babic, Ana; Wolpin, Brian M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM bwolpin@partners.org NR 5 TC 0 Z9 0 U1 4 U2 10 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 2016 VL 62 IS 2 BP 307 EP 309 DI 10.1373/clinchem.2015.246538 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA DC8KR UT WOS:000369468900001 PM 26721295 ER PT J AU Romanos, GE Biltucci, MT Kokaras, A Paster, BJ AF Romanos, Georgios E. Biltucci, Mary Therese Kokaras, Alexis Paster, Bruce J. TI Bacterial Composition at the Implant-Abutment Connection under Loading in vivo SO CLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH LA English DT Article DE bacteria; immediate loading; implant-abutment interface; platform switching ID VITRO EVALUATION; INTERFACE; INFLAMMATION; PROSTHESES; MICROARRAY; SYSTEMS; TIME AB PurposePlatform-switched implants have been demonstrated to prevent bone loss after loading. The present study evaluated bacterial composition of sites from implant-abutment connections of immediately loaded implants, which were placed in the anterior mandible. Ten patients participated in this study. Materials and MethodsA and B implant systems with two different prosthetic connections (Morse tapered vs internal polygonal butt-joint connections, respectively) were placed and loaded for 2 years. The abutments were removed (AB sample) after careful decontamination. Bacterial sampling of the abutments, inner part of the implants (before/visit 1 and after rinsing with chlorhexidine [CHX]/visit 2), and after new abutment connection and loading for 1 additional month, a new sampling (visit 3) was taken to compare the bacteria composition in association with the two connections. Bacterial profiles of samples were determined by using the human oral microbe identification microarray. ResultsA total of 240 samples were analyzed taken at different time intervals. Nonparametric statistical analysis (Wilcoxon Rank sum) with uncorrected alpha (p<.05) and after corrections (Benjamini-Hochberg) found no statistical significance between the two connections. No significant changes in the overall microbial profiles were detected at the different time intervals. However, there were trends toward presence of periodontitis-associated species at the B implants in all samples (AB, visit 1, even after CHX irrigation) and after decontamination, abutment replacement, and 1-month loading period. ConclusionsCHX irrigation does not seem to have any effect on decontamination of connections. As shown previously, there is significantly more bone loss around B implants compared with A implants. Although there was no statistical difference in the microbial profiles, there was indeed a trend for the presence of typical periodontal pathogens associated with the internal polygonal butt-joint connection. A possible scenario is that this connection tends to harbor the pathogens that may be involved in subsequent bone loss. C1 [Romanos, Georgios E.] Univ Rochester, Eastman Inst Oral Hlth, Dept Periodontol, Rochester, NY USA. [Biltucci, Mary Therese] Univ Rochester, Dept Dent, Rochester, NY USA. [Kokaras, Alexis; Paster, Bruce J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. RP Romanos, GE (reprint author), Univ Rochester, Eastman Inst Oral Hlth, Dept Periodontol, Rochester, NY USA.; Romanos, GE (reprint author), SUNY Stony Brook, Sch Dent Med, Dept Dent Med, Dept Periodontol, 106 Rockland Hall, Stony Brook, NY 11794 USA. EM georgios.romanos@stonybrook.edu FU Dentsply-Implants FX The authors would like to thank Dr. Robert Quivey Jr., PhD, and Roberta Faustoferri (Center of Oral Biology, University of Rochester, Rochester, NY) for their laboratory support in this study and Dr. Joerg Nonhoff (Dentsply-Implants, Mannheim, Germany) for his scientific contribution in this project. The study was supported by Dentsply-Implants. NR 32 TC 5 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1523-0899 EI 1708-8208 J9 CLIN IMPLANT DENT R JI Clin. Implant Dent. Relat. Res. PD FEB PY 2016 VL 18 IS 1 BP 138 EP 145 DI 10.1111/cid.12270 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DC6OM UT WOS:000369339400016 PM 25195711 ER PT J AU ter Maaten, JM Valente, MAE Metra, M Bruno, N O'Connor, CM Ponikowski, P Teerlink, JR Cotter, G Davison, B Cleland, JG Givertz, MM Bloomfield, DM Dittrich, HC van Veldhuisen, DJ Hillege, HL Damman, K Voors, AA AF ter Maaten, Jozine M. Valente, Mattia A. E. Metra, Marco Bruno, Noemi O'Connor, Christopher M. Ponikowski, Piotr Teerlink, John R. Cotter, Gad Davison, Beth Cleland, John G. Givertz, Michael M. Bloomfield, Daniel M. Dittrich, Howard C. van Veldhuisen, Dirk J. Hillege, Hans L. Damman, Kevin Voors, Adriaan A. TI A combined clinical and biomarker approach to predict diuretic response in acute heart failure SO CLINICAL RESEARCH IN CARDIOLOGY LA English DT Article DE Diuretic response; Heart failure; Biomarkers; Prediction ID BLOOD UREA NITROGEN; PROGNOSTIC VALUE; THERAPY; ATHEROSCLEROSIS; TRANSPORT; CHLORIDE; RECEPTOR AB Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic response in acute heart failure (AHF). We investigated explanatory and predictive models for diuretic response-weight loss at day 4 per 40 mg of furosemide-in 974 patients with AHF included in the PROTECT trial. Biomarkers, addressing multiple pathophysiological pathways, were determined at baseline and after 24 h. An explanatory baseline biomarker model of a poor diuretic response included low potassium, chloride, hemoglobin, myeloperoxidase, and high blood urea nitrogen, albumin, triglycerides, ST2 and neutrophil gelatinase-associated lipocalin (r (2) = 0.086). Diuretic response after 24 h (early diuretic response) was a strong predictor of diuretic response (beta = 0.467, P < 0.001; r (2) = 0.523). Addition of diuretic response after 24 h to biomarkers and clinical characteristics significantly improved the predictive model (r (2) = 0.586, P < 0.001). Biomarkers indicate that diuretic unresponsiveness is associated with an atherosclerotic profile with abnormal renal function and electrolytes. However, predicting diuretic response is difficult and biomarkers have limited additive value. Patients at risk of poor diuretic response can be identified by measuring early diuretic response after 24 h. C1 [ter Maaten, Jozine M.; Valente, Mattia A. E.; van Veldhuisen, Dirk J.; Hillege, Hans L.; Damman, Kevin; Voors, Adriaan A.] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. [Metra, Marco] Univ Brescia, Brescia, Italy. [Bruno, Noemi] Univ Roma La Sapienza, Dept Cardiovasc Sci, Piazzale Aldo Moro 5, I-00185 Rome, Italy. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cotter, Gad; Davison, Beth] Momentum Res, Durham, NC USA. [Cleland, John G.] Univ Hull, Kingston Upon Hull, Yorks, England. [Givertz, Michael M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Dittrich, Howard C.] Univ Iowa, Carver Coll Med, Cardiovasc Res Ctr, Iowa City, IA USA. [Hillege, Hans L.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. RP Voors, AA (reprint author), Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM a.a.voors@umcg.nl RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Cleland, John/0000-0002-1471-7016 FU NovaCardia, Merck FX The PROTECT trial was supported by NovaCardia, a subsidiary of Merck. Alere and Singulex kindly provided assays and performed biomarker measurements. NR 27 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-0684 EI 1861-0692 J9 CLIN RES CARDIOL JI Clin. Res. Cardiol. PD FEB PY 2016 VL 105 IS 2 BP 145 EP 153 DI 10.1007/s00392-015-0896-2 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DC5IM UT WOS:000369254700006 PM 26280875 ER PT J AU Hall, GM Shanmugan, S Bleier, JIS Jeganathan, AN Epstein, AJ Paulson, EC AF Hall, G. M. Shanmugan, S. Bleier, J. I. S. Jeganathan, A. N. Epstein, A. J. Paulson, E. C. TI Colorectal specialization and survival in colorectal cancer SO COLORECTAL DISEASE LA English DT Article DE Colon cancer; rectal cancer; specialization; survival ID II COLON-CANCER; HOSPITAL VOLUME; RECTAL-CANCER; UNITED-STATES; STAGE-II; ADJUVANT THERAPY; SURGERY; OUTCOMES; PREDICTORS; RECURRENCE AB AimIt is recognized that higher surgeon volume is associated with improved survival in colorectal cancer. However, there is a paucity of national studies that have evaluated the relationship between surgical specialization and survival. MethodWe used the Surveillance, Epidemiology, and End Results Medicare cancer registry to examine the association between colorectal specialization (CRS) and disease-specific survival (DSS) between 2001 and 2009. A total of 21432 colon cancer and 5893 rectal cancer patients who underwent elective surgical resection between 2001 and 2009 were evaluated. Univariate and multivariate Cox survival analysis was used to identify the association between surgical specialization and cancer-specific survival. ResultsColorectal specialists performed 16.3% of the colon and 27% of the rectal resections. On univariate analysis, specialization was associated with improved survival in Stage II and Stage III colon cancer and Stage II rectal cancer. In multivariate analysis, however, CRS was associated with significantly improved DSS only in Stage II rectal cancer [hazard ratio (HR) 0.70, P=0.03]. CRS was not significantly associated with DSS in either Stage I (colon HR 1.14, P=0.39; rectal HR 0.1.26, P=0.23) or Stage III (colon HR 1.06, P=0.52; rectal HR 1.08, P=0.55) disease. When analysis was limited to high volume surgeons only, the relationship between CRS and DSS was unchanged. ConclusionsCRS is associated with improved DSS following resection of Stage II rectal cancer. A combination of factors may contribute to long-term survival in these patients, including appropriate surgical technique, multidisciplinary treatment decisions and guideline-adherent surveillance. CRS probably contributes positively to these factors resulting in improved survival. C1 [Hall, G. M.; Shanmugan, S.; Bleier, J. I. S.; Paulson, E. C.] Univ Penn, Dept Gen Surg, Div Colon & Rectal Surg, Philadelphia, PA 19104 USA. [Jeganathan, A. N.] Univ Penn, Dept Gen Surg, Philadelphia, PA 19104 USA. [Epstein, A. J.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Epstein, A. J.] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Paulson, E. C.] Philadelphia VA Med Ctr, Dept Gen Surg, 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 NR 26 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8910 EI 1463-1318 J9 COLORECTAL DIS JI Colorectal Dis. PD FEB PY 2016 VL 18 IS 2 BP O51 EP O60 DI 10.1111/codi.13246 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA DD2GH UT WOS:000369740200001 PM 26708838 ER PT J AU Kamran, SC Hong, TS Wo, JY AF Kamran, Sophia C. Hong, Theodore S. Wo, Jennifer Y. TI Advances in the Management of Gastric and Gastroesophageal Cancers SO CURRENT ONCOLOGY REPORTS LA English DT Review DE Gastric cancer; Gastroesophageal junction cancer; Radiation therapy; Chemoradiation; Trimodality therapy ID PHASE-III TRIAL; RANDOMIZED CONTROLLED-TRIAL; COMBINED-MODALITY THERAPY; LYMPH-NODE DISSECTION; ESOPHAGEAL CANCER; PREOPERATIVE CHEMORADIATION; PERIOPERATIVE CHEMOTHERAPY; ADJUVANT CAPECITABINE; JUNCTION CANCER; OPEN-LABEL AB Management of gastric and gastroesophageal cancers is a complex, evolving paradigm. Involvement of multimodality specialties is the key. In gastric cancer, data are conflicting with regard to the specific roles of surgery, chemotherapy, and radiation, particularly between Asian and Western studies. However, current ongoing phase III trials will further elucidate the optimal treatment for this heterogeneous disease. For resectable gastroesophageal junction (GEJ) tumors, the publication of a landmark study in 2012 out of the Netherlands revealed a clear benefit in the utilization of trimodality therapy. This changed practice almost immediately around the world. In unresectable gastroesophageal disease, chemoradiation has been firmly established as a paradigm for treatment. The optimal chemotherapy regimen is still in flux. However, for both gastric and GEJ tumors, technological breakthroughs in genomics and pharmacologic targeting will soon provide physicians more options in the armamentarium to fight these diseases and, one day, individually personalize treatment. C1 [Kamran, Sophia C.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Hong, Theodore S.; Wo, Jennifer Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Wo, JY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. EM skamran@partners.org; tshong1@mgh.harvard.edu; jwo@mgh.harvard.edu OI Kamran, Sophia/0000-0001-9283-6515 NR 44 TC 1 Z9 1 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD FEB PY 2016 VL 18 IS 2 AR 13 DI 10.1007/s11912-015-0493-6 PG 9 WC Oncology SC Oncology GA DC5NB UT WOS:000369266600006 PM 26769118 ER PT J AU Leung, MW Goldfarb, S Dizon, DS AF Leung, Margaret W. Goldfarb, Shari Dizon, Don S. TI Communication About Sexuality in Advanced Illness Aligns With a Palliative Care Approach to Patient-Centered Care SO CURRENT ONCOLOGY REPORTS LA English DT Review DE Palliative care; Sexuality; Communication ID CANCER-PATIENTS; OVARIAN-CANCER; LUNG-CANCER; HEALTH; INTIMACY; SURVIVORS; SEX; BARRIERS; WOMEN; RECOMMENDATIONS AB Treatment-related sexual complications are common in cancer patients although rarely discussed in the palliative care setting. Sexuality is an important survivorship issue and remains relevant even in the terminal setting. There are multiple barriers in dialoguing about intimacy and sexual functioning from the patient and provider perspectives. Palliative care providers, while not expected to be sexual health experts, can provide comprehensive patient-centered care by including sexual health as part of their evaluation. They can explore how sexual dysfunction can impair functioning and utilize an interdisciplinary approach to manage symptoms. Palliative care providers can help patients identify their goals of care and explore what anticipated sexual changes and treatrelated side effects are tolerable and intolerable to the patient's quality of life. Principles on addressing sexuality in the palliative setting and practical ways of incorporating sexual history into the palliative care assessment are provided. C1 [Leung, Margaret W.] Kaiser Permanente, 1600 Eureka Rd, Roseville, CA 95661 USA. [Dizon, Don S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. [Goldfarb, Shari] Mem Sloan Kettering Canc Ctr, Breast & Imaging Ctr, 300 East 66th St, New York, NY 10065 USA. RP Leung, MW (reprint author), Kaiser Permanente, 1600 Eureka Rd, Roseville, CA 95661 USA. EM margaret.w.leung@kp.org; goldfars@mskcc.org; ddizon@partners.org FU NCI NIH HHS [P30 CA008748] NR 53 TC 0 Z9 1 U1 3 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD FEB PY 2016 VL 18 IS 2 AR 11 DI 10.1007/s11912-015-0497-2 PG 6 WC Oncology SC Oncology GA DC5NB UT WOS:000369266600004 PM 26769116 ER PT J AU Villar, J Blanco, J Kacmarek, RM AF Villar, Jesus Blanco, Jesus Kacmarek, Robert M. TI Current incidence and outcome of the acute respiratory distress syndrome SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE acute respiratory distress syndrome; incidence; outcome; protective ventilation ID ACUTE LUNG INJURY; PROSPECTIVE COHORT; BERLIN DEFINITION; CLINICAL-TRIALS; INTENSIVE-CARE; TIDAL VOLUMES; MORTALITY; VENTILATION; ARDS; METAANALYSIS AB Purpose of review This article discusses recently published articles reporting the incidence and outcome of patients with the acute respiratory distress syndrome (ARDS). This is a difficult task since there is a marked variability regarding the methodology of the few, large epidemiological, and observational studies on ARDS. Recent findings The review will mainly focus on publications from the past 18 months. We have reviewed new epidemiological studies reporting population-based incidence of ARDS. Also, we have reviewed the data on survival reported in observational and randomized controlled trials, discussed how the current ARDS definition modifies the true incidence of ARDS, and briefly mentioned recent approaches that appear to improve ARDS outcome. Summary On the basis of current evidence, it seems that the incidence and overall hospital mortality of ARDS has not changed substantially in the last decade. Independent of the definition used for identification of ARDS patients, reported population-based incidence of ARDS is an order of magnitude lower in Europe than in the USA. Current hospital mortality of combined moderate and severe ARDS reported in observational studies is greater than 40%. C1 [Villar, Jesus; Blanco, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain. [Villar, Jesus] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr Biomed Sci, 30 Bond St, Toronto, ON M5B 1W8, Canada. [Blanco, Jesus] Hosp Univ Rio Hortega, Intens Care Unit, Valladolid, Spain. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Resp Care, Boston, MA USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care Med, Boston, MA USA. RP Villar, J (reprint author), Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Barranco Ballena S-N,4th Floor,South Wing, Las Palmas Gran Canaria 35019, Spain. EM jesus.villar54@gmail.com FU Instituto de Salud Carlos III, Spain [CB06/06/1088, PI10/0393, PI13/0119]; Asociacion Cientifica Pulmon y Ventilacion Mecanica FX This study is supported in part by Instituto de Salud Carlos III, Spain (CB06/06/1088, PI10/0393, PI13/0119), and Asociacion Cientifica Pulmon y Ventilacion Mecanica. NR 34 TC 11 Z9 11 U1 5 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-5295 EI 1531-7072 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD FEB PY 2016 VL 22 IS 1 BP 1 EP 6 DI 10.1097/MCC.0000000000000266 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA DC9KD UT WOS:000369539500001 PM 26645551 ER PT J AU Gong, MN Thompson, BT AF Gong, Michelle Ng Thompson, B. Taylor TI Acute respiratory distress syndrome: shifting the emphasis from treatment to prevention SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE acute respiratory distress syndrome; clinical trials; prevention ID ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; LOWER TIDAL VOLUMES; SURGICAL-PATIENTS; CLINICAL-TRIAL; MULTICENTER COHORT; PULMONARY-FUNCTION; SEVERE SEPSIS AB Purpose of review Although results from clinical trials have advanced the treatment of acute respiratory distress syndrome (ARDS), mortality remains high. More recently, focus has shifted from treatment of ARDS to early identification and prevention in at-risk populations. Recent findings There have been 30 published and registered clinical trials with either the primary or secondary goal of reducing ARDS. Summary With this change in paradigm, come additional challenges and consideration in study design that depends not only on the intervention but also whether the intervention aims for a primary, secondary, or tertiary prevention of ARDS that targets a patient population for universal, selective, or indicated prevention. These epidemiologic concepts of prevention in public health also apply to ARDS and are relevant to the study population to target, the timing of the intervention relative to critical illness, the study design and outcomes to measure in an ARDS prevention study. This shift in focus is reflected by the new National Heart Lung Blood Institute Prevention and Early Treatment of Acute Lung Injury network, and signifies an overall movement away from reacting to and supporting acute organ failure after it is established to early detection and prevention in acute critical illness wherever and whenever it may occur. C1 [Gong, Michelle Ng] Montefiore Med Ctr, Dept Med, Div Crit Care Med, Bronx, NY 10467 USA. [Gong, Michelle Ng] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Thompson, B. Taylor] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Pulm & Crit Care Unit, Boston, MA USA. RP Gong, MN (reprint author), Montefiore Med Ctr, Dept Med, Div Crit Care Med, Crit Care Med Adm Off, Ground Floor,Gold Zone,111 East 210th St, Bronx, NY 10467 USA. EM mgong@montefiore.org FU National Heart, Lung, Blood Institute (NHLBI) at the National Institute of Health FX The work is supported by the National Heart, Lung, Blood Institute (NHLBI) at the National Institute of Health. NR 59 TC 4 Z9 4 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-5295 EI 1531-7072 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD FEB PY 2016 VL 22 IS 1 BP 21 EP 37 DI 10.1097/MCC.0000000000000275 PG 17 WC Critical Care Medicine SC General & Internal Medicine GA DC9KD UT WOS:000369539500004 PM 26645554 ER PT J AU Levitsky, LL AF Levitsky, Lynne L. TI Nutrition and growth - a multitude of manifestations and room for further investigation SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Editorial Material ID ADIPOSE-TISSUE; LINEAR GROWTH; OBESITY; HEIGHT; FAT C1 [Levitsky, Lynne L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Levitsky, LL (reprint author), Harvard Univ, Sch Med, Pediat, 175 Cambridge St,5th Floor, Boston, MA 02114 USA.; Levitsky, LL (reprint author), Massachusetts Gen Hosp, Pediat Endocrinol, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM LLevitsky@mgh.harvard.edu NR 23 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 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2016 VL 23 IS 1 BP 48 EP 50 DI 10.1097/MED.0000000000000223 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD1BW UT WOS:000369657100008 PM 26702850 ER PT J AU Meya, DB Manabe, YC Boulware, DR Janoff, EN AF Meya, David B. Manabe, Yukari C. Boulware, David R. Janoff, Edward N. TI The immunopathogenesis of cryptococcal immune reconstitution inflammatory syndrome: understanding a conundrum SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE cryptococcus; cryptococcal meningitis; HIV; immunopathogenesis; immune reconstitution inflammatory syndrome ID ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; HIV-INFECTED PATIENTS; RESOURCE-LIMITED SETTINGS; CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; CEREBROSPINAL-FLUID; RESTORATION DISEASE; FUNGAL-INFECTIONS; PRIMARY IMMUNODEFICIENCIES AB Purpose of reviewCryptococcal meningitis causes significant mortality among HIV-infected patients, despite antifungal therapy and use of antiretroviral therapy (ART). In patients with cryptococcal meningitis, ART is often complicated by immune reconstitution inflammatory syndrome (IRIS), manifesting as unmasking of previously unrecognized subclinical infection (unmasking CM-IRIS) or paradoxical worsening of symptoms in the central nervous system after prior improvement with antifungal therapy (paradoxical CM-IRIS). We review our current understanding of the pathogenesis of this phenomenon, focusing on unifying innate and adaptive immune mechanisms leading to the development of this often fatal syndrome.Recent findingsWe propose that HIV-associated CD4(+) T-cell depletion, chemokine-driven trafficking of monocytes into cerebrospinal fluid in response to cryptococcal meningitis, and poor localized innate cytokine responses lead to inadequate cryptococcal killing and clearance of the fungus. Subsequent ART-associated recovery of T-cell signaling and restored cytokine responses, characterized by IFN- production, triggers an inflammatory response. The inflammatory response triggered by ART is dysregulated because of impaired homeostatic and regulatory mechanisms, culminating in the development of CM-IRIS.SummaryDespite our incomplete understanding of the immunopathogenesis of CM-IRIS, emerging data exploring innate and adaptive immune responses could be exploited to predict, prevent and manage CM-IRIS and associated morbid consequences. C1 [Meya, David B.] Makerere Univ, Infect Dis Inst, Kampala 22418, Uganda. [Meya, David B.; Boulware, David R.] Univ Minnesota, Dept Med, Ctr Infect Dis & Microbiol Translat Res, Box 736 UMHC, Minneapolis, MN 55455 USA. [Meya, David B.] Makerere Univ, Sch Med, Coll Hlth Sci, Kampala 22418, Uganda. [Manabe, Yukari C.] Johns Hopkins Univ, Dept Med, Div Infect Dis, Baltimore, MD USA. [Janoff, Edward N.] Univ Colorado, Mucosal & Vaccine Res Program Colorado MAVRC, Denver, CO 80202 USA. [Janoff, Edward N.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Meya, DB (reprint author), Makerere Univ, Infect Dis Inst, Coll Hlth Sci, Kampala 22418, Uganda. EM david.meya@gmail.com OI Boulware, David/0000-0002-4715-0060 FU National Institutes of Health [R01AI078934, U01AI089244, R21NS065713, R01AI108479, T32AI055433, K24AI096925]; Welcome Trust Training Health Researchers into Vocational Excellence (THRiVE) in East Africa [087540, AI108479]; Veterans Affairs Research Service FX This work supported by the National Institutes of Health (R01AI078934, U01AI089244, R21NS065713, R01AI108479, T32AI055433) to D.M. and D.B.; K24AI096925 to P.B.; the Welcome Trust Training Health Researchers into Vocational Excellence (THRiVE) in East Africa, grant number 087540 to D.M.; AI108479 to E.J.; and the Veterans Affairs Research Service. NR 108 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 0951-7375 EI 1473-6527 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD FEB PY 2016 VL 29 IS 1 BP 10 EP 22 DI 10.1097/QCO.0000000000000224 PG 13 WC Infectious Diseases SC Infectious Diseases GA DC9NZ UT WOS:000369549600002 PM 26658650 ER PT J AU Shepard, DS Daley, MC Neuman, MJ Blaakman, AP Mckay, JR AF Shepard, Donald S. Daley, Marilyn C. Neuman, Matthew J. Blaakman, Aaron P. McKay, James R. TI Telephone-based continuing care counseling in substance abuse treatment: Economic analysis of a randomized trial SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol and cocaine dependence; Continuing care alternatives; Telephone-based continuing care; Relapse prevention ID BENEFIT-COST-ANALYSIS; RELAPSE PREVENTION; TREATMENT SERVICES; USE DISORDERS; ALCOHOL-CONSUMPTION; ADDICTION TREATMENT; SMOKING-CESSATION; PROBLEM DRINKERS; CLINICAL-TRIALS; FOLLOW-UP AB Purpose: To investigate whether telephone-based continuing care (TEL) is a promising alternative to traditional face-to-face counseling for clients in treatment for substance abuse. Methods: Patients with alcohol and/or cocaine dependence who had completed a 4-week intensive outpatient program were randomly assigned through urn randomization into one of three 12-week interventions: standard continuing care (STD), in-person relapse prevention (RP), or telephone-based continuing care (TEL). This study performed cost, cost-effectiveness, and cost-benefit analyses of TEL and RP compared to STD, using results from the randomized clinical trial with two years of follow up (359 participants). In addition, the study examined the potential moderating effect of baseline patient costs on economic outcomes. Results: The study found that TEL was less expensive per client from the societal perspective ($569) than STD ($870) or RP ($1684). TEL also was also significantly more effective, with an abstinence rate of 57.1% compared to 46.7% for STD (p <0.05). Thus TEL dominated STD, with a highly favorable negative incremental cost-effectiveness ratio (-$1400 per abstinent year). TEL also proved favorable under a benefit-cost perspective. Conclusions: TEL proved to be a cost-effective and cost-beneficial contributor to long-term recovery over two years. Because TEL dominated STD care interventions, wider adoption should be considered. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Shepard, Donald S.; Daley, Marilyn C.] Brandeis Univ, Heller Sch Social Policy & Management, Schneider Inst Hlth Policy, Waltham, MA 02454 USA. [Neuman, Matthew J.] US Dept Vet Affairs, Program Evaluat & Resource Ctr, VA Palo Alto Hlth Care Syst, Menlo Pk Div, 795 Willow Rd, Menlo Pk, CA 94025 USA. [Neuman, Matthew J.] US Dept Vet Affairs, Hlth Care Financing & Econ, VA Boston Hlth Care Syst, 150 South Huntington Ave, Boston, MA 02130 USA. [Blaakman, Aaron P.] 203 Candia Lane, Cary, NC 27519 USA. [McKay, James R.] Univ Penn, Dept Psychiat, Perelman Sch Med, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. [McKay, James R.] US Dept Vet Affairs, Crescenz VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. RP Shepard, DS (reprint author), Brandeis Univ, Heller Sch Social Policy & Management, Schneider Inst Hlth Policy, Waltham, MA 02454 USA. EM shepard@brandeis.edu FU NIAAA NIH HHS [R01 AA010341]; NIDA NIH HHS [R01 DA010262, K02 DA000361, K24 DA029062] NR 49 TC 0 Z9 0 U1 2 U2 6 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 FEB 1 PY 2016 VL 159 BP 109 EP 116 DI 10.1016/j.drugalcdep.2015.11.034 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DC8LX UT WOS:000369472200015 PM 26718395 ER PT J AU Lee, S Ko, BJ Gong, Y Han, K Lee, A Han, BD Yoon, YJ Park, S Kim, JH Mantzoros, CS AF Lee, Saehyun Ko, Byung-Joon Gong, Younghoon Han, Kyungdo Lee, Anna Han, Byoung-Duck Yoon, Yeo Joon Park, Siyoung Kim, Jung-Hyun Mantzoros, Christos S. TI Self-reported eating speed in relation to non-alcoholic fatty liver disease in adults SO EUROPEAN JOURNAL OF NUTRITION LA English DT Article DE Eating behavior; Non-alcoholic fatty liver disease; Insulin resistance; Obesity ID AGED JAPANESE MEN; TYPE-2 DIABETES-MELLITUS; GLUCAGON-LIKE PEPTIDE-1; INSULIN-RESISTANCE; ENERGY-INTAKE; GUT HORMONES; FAST LEADS; OBESITY; WOMEN; RISK AB Non-alcoholic fatty liver disease (NAFLD), known to be related to insulin resistance, has been the focus of intensive research efforts due to its increasing prevalence and clinical significance. Rapid eating behavior is another emerging health issue associated with insulin resistance. We aimed to clarify the correlation between self-reported eating speed and NAFLD, both known to be related to insulin resistance. A cross-sectional study was conducted during routine medical checkups on 7,917 consecutively enrolled participants. Anthropometric, biochemical, nutritional, and social parameters were checked. The self-reported eating speed per their usual meal (< 5, 5-10, 10-15, and more than 15 min) was recorded by a registered dietitian. The faster eating groups had a higher proportion of NAFLD, and the grade of NAFLD was advanced. After controlling for anthropometric, cardiometabolic, social, and nutritional parameters, the fastest eating group (< 5 min) showed an increased risk of NAFLD compared with the lowest eating speed group (a parts per thousand yen15 min) both in total [odds ratio (OR) 1.81, 95 % confidence interval (CI) 1.24-2.63] and the participants with BMI < 25 kg/m(2) (OR 1.79, 95 % CI 1.22-2.61). As the self-reported eating speed increased, the risk of NAFLD also increased in total and those with BMI < 25 kg/m(2) (P for trend < 0.001). Fast eating is associated with an increased risk of the presence and grade of NAFLD in Korean adults, especially those with BMI < 25 kg/m(2), since presence of overweight or obesity may be overwhelming the effect on NAFLD. C1 [Lee, Saehyun; Ko, Byung-Joon; Gong, Younghoon; Yoon, Yeo Joon; Park, Siyoung] Korea Univ, Dept Family Med, Coll Med, Seoul 136705, South Korea. [Ko, Byung-Joon; Mantzoros, Christos S.] Harvard Univ, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Ko, Byung-Joon] Sungkyunkwan Univ, Total Healthcare Ctr, Kangbuk Samsung Hosp, Sch Med, Seoul 100742, South Korea. [Han, Kyungdo] Catholic Univ, Dept Biostat, Coll Med, Seoul 137701, South Korea. [Lee, Anna] Univ Pacific, Sch Phys Assistant Studies, Coll Hlth Profess, Hillsboro, OR 97123 USA. [Han, Byoung-Duck] SahmYook Med Ctr, Dept Family Med, Seoul 130711, South Korea. [Kim, Jung-Hyun] Seoul Natl Univ, Grad Sch Publ Hlth, Dept Publ Hlth, Seoul 151742, South Korea. [Mantzoros, Christos S.] Harvard Univ, Endocrinol Sect, Boston VA Healthcare Syst, Sch Med, Boston, MA 02130 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu NR 33 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1436-6207 EI 1436-6215 J9 EUR J NUTR JI Eur. J. Nutr. PD FEB PY 2016 VL 55 IS 1 BP 327 EP 333 DI 10.1007/s00394-015-0851-z PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DC6DJ UT WOS:000369309700031 PM 25648740 ER PT J AU Hoggatt, J Hoggatt, AF Tate, TA Fortman, J Pelus, LM AF Hoggatt, Jonathan Hoggatt, Amber F. Tate, Tiffany A. Fortman, Jeffrey Pelus, Louis M. TI Bleeding the laboratory mouse: Not all methods are equal SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID CLINICAL PATHOLOGY PARAMETERS; BLOOD COLLECTION; SAMPLING SITE; MICE; PLEXUS; RATS AB The laboratory mouse is the model most frequently used in hematologic studies and assessment of blood parameters across a broad range of disciplines. Often, analysis of blood occurs in a nonterminal manner. However, the small body size of the mouse limits collection based on volume, frequency, and accessible sites. Commonly used sites in the mouse include the retro-orbital sinus, facial vein, tail vein, saphenous vein, and heart. The method of blood acquisition varies considerably across laboratories and is often not reported in detail. In this study, we report significant alterations in blood parameters, particularly of total white blood cells, specific populations of dendritic cells and myeloid-derived suppressor cells, and hematopoietic progenitor cells, as a result of site and manner of sampling. Intriguingly, warming of mice prior to tail bleeding was found to significantly alter blood values. Our findings suggest that the same method should be used across an entire study, that mice should be warmed prior to tail bleeds to make levels uniform, and that accurate description of bleeding methods in publications should be provided to allow for interpretation of comparative reports and inter and intralaboratory experimental variability. Copyright (C) 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. C1 [Hoggatt, Jonathan; Tate, Tiffany A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Ctr Transplantat Sci,Med Sch, Boston, MA 02114 USA. [Hoggatt, Amber F.] Harvard Univ, Sch Med, Ctr Comparat Med, Boston, MA USA. [Fortman, Jeffrey] Univ Illinois, Biol Resources Lab, Chicago, IL USA. [Pelus, Louis M.] Indiana Univ Sch Med, Microbiol & Immunol, Indianapolis, IN 46202 USA. RP Hoggatt, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Transplantat Sci, 149 13th St CNY149,Room 5-301, Boston, MA 02129 USA.; Pelus, LM (reprint author), Indiana Univ Sch Med, Dept Microbiol & Immunol, 950 West Walnut St,R2-302, Indianapolis, IN 46202 USA. EM hoggatt.jonathan@mgh.harvard.edu; lpelus@iupui.edu FU NIH [HL069669, HL096305, HL007910, HL119559] FX This work was supported by NIH Grants HL069669 and HL096305 to LMP. JH was supported by NIH Training Grant HL007910 and is currently supported by HL119559. Flow cytometry was performed in the Flow Cytometry Resource Facility of the Indiana University Simon Cancer Center (NCI P30 CA082709). NR 16 TC 1 Z9 1 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD FEB PY 2016 VL 44 IS 2 BP 132 EP 137 DI 10.1016/j.exphem.2015.10.008 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA DC8KY UT WOS:000369469700007 PM 26644183 ER PT J AU Jensen, DM Ohning, GV Kovacs, TOG Jutabha, R Ghassemi, K Dulai, GS Machicado, GA AF Jensen, Dennis M. Ohning, Gordon V. Kovacs, Thomas O. G. Jutabha, Rome Ghassemi, Kevin Dulai, Gareth S. Machicado, Gustavo A. TI Natural history of definitive diverticular hemorrhage based on stigmata of recent hemorrhage and colonoscopic Doppler blood flow monitoring for risk stratification and definitive hemostasis SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID BLEEDING COLONIC DIVERTICULA; ENDOSCOPIC HEMOSTASIS; URGENT COLONOSCOPY; SEVERE HEMATOCHEZIA; MASSIVE HEMORRHAGE; DIAGNOSIS; MANAGEMENT; VESSEL; INJECTION; THERAPY AB Background and Aims: Few prospective reports describe the short-term natural history of colon diverticular hemorrhage based on stigmata of recent hemorrhage, and none include blood flow detection for risk stratification or as a guide to definitive hemostasis. Our purposes were to report the 30-day natural history of definitive diverticular hemorrhage based on stigmata and to describe Doppler probe blood flow detection as a guide to definitive hemostasis. Methods: Different cohorts of patients with severe diverticular bleeding and stigmata on urgent colonoscopy are reported. For 30-day natural history, patients were treated medically. If severe rebleeding occurred, they had surgical or angiographic treatment. We report natural history with major stigmata (active bleeding, visible vessel, or adherent clot) and no stigmata or flat spots after clots were washed away. We also report Doppler probe detection of arterial blood flow underneath stigmata before and after hemostasis in a recent cohort. Results: For natural history, patients with major stigmata treated medically had 65.8% (25/38) rebleeding rates, and 44.7% (17/38) had intervention for hemostasis. Patients with spots or clean bases had no rebleeding. A Doppler probe detected arterial blood flow in 92% of major stigmatadnone after hemostasisdand there was no rebleeding. Conclusions: (1) Patients with major stigmata treated medically had high rates of rebleeding and intervention for hemostasis. (2) Patients with clean diverticula or only flat spots had no rebleeding. (3) High rates of arterial blood flow were detected under major stigmata with a Doppler probe, but with obliteration by hemostasis no rebleeding occurred. C1 [Jensen, Dennis M.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Ulcer Res & Educ,Dept Med Ronald Reagan UCLA, Digest Dis Res Ctr,Vet Affairs Greater Los Angele, Los Angeles, CA 90095 USA. Vet Affairs West Los Angeles Med Ctr, Los Angeles, CA USA. RP Jensen, DM (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr DDRC, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU Clinical Veterans Affairs Merit Review Grant, NIH [P30 AM41301]; Center for Ulcer Research and Education Digestive Diseases Research Center core grant; Vascular Technologies Incorporated (VTI) FX These studies were supported partially by a Clinical Veterans Affairs Merit Review Grant (D. Jensen, PI), NIH P30 AM41301, a Center for Ulcer Research and Education Digestive Diseases Research Center core grant (human studies core), and by Vascular Technologies Incorporated (VTI), who donated colon Doppler endoscopic probes. D. Jensen is a consultant for VTI and is a speaker for BSC. All other authors disclosed no financial relationships relevant to this publication. NR 33 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 2016 VL 83 IS 2 BP 416 EP 423 DI 10.1016/j.gie.2015.07.033 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DC5AK UT WOS:000369232000021 PM 26227931 ER PT J AU Pawlyk, BS Bulgakov, OV Sun, X Adamian, M Shu, X Smith, AJ Berson, EL Ali, RR Khani, S Wright, AF Sandberg, MA Li, T AF Pawlyk, B. S. Bulgakov, O. V. Sun, X. Adamian, M. Shu, X. Smith, A. J. Berson, E. L. Ali, R. R. Khani, S. Wright, A. F. Sandberg, M. A. Li, T. TI Photoreceptor rescue by an abbreviated human RPGR gene in a murine model of X-linked retinitis pigmentosa SO GENE THERAPY LA English DT Article ID LEBER CONGENITAL AMAUROSIS; RETINAL DEGENERATION; EXON ORF15; REPLACEMENT THERAPY; CANINE MODEL; MOUSE MODELS; MUTATIONS; CONE; ROD; RP2 AB The X-linked RP3 gene codes for the ciliary protein RPGR and accounts for over 10% of inherited retinal degenerations. The critical RPGR-ORF15 splice variant contains a highly repetitive purine-rich linker region that renders it unstable and difficult to adapt for gene therapy. To test the hypothesis that the precise length of the linker region is not critical for function, we evaluated whether adeno-associated virus-mediated replacement gene therapy with a human ORF15 variant containing in-frame shortening of the linker region could reconstitute RPGR function in vivo. We delivered human RPGR-ORF15 replacement genes with deletion of most (314 codons, 'short form') or 1/3 (126 codons, 'long form') of the linker region to Rpgr null mice. Human RPGR-ORF15 expression was detected post treatment with both forms of ORF15 transgenes. However, only the long form correctly localized to the connecting cilia and led to significant functional and morphological rescue of rods and cones. Thus the highly repetitive region of RPGR is functionally important but that moderate shortening of its length, which confers the advantage of added stability, preserves its function. These findings provide a theoretical basis for optimizing replacement gene design in clinical trials for X-linked RP3. C1 [Pawlyk, B. S.; Adamian, M.; Berson, E. L.; Sandberg, M. A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Sch Med, Boston, MA USA. [Bulgakov, O. V.; Sun, X.; Li, T.] NEI, 6 Ctr Dr, Bethesda, MD 20892 USA. [Shu, X.; Wright, A. F.] Univ Edinburgh, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Shu, X.] Glasgow Caledonian Univ, Dept Life Sci, Glasgow G4 0BA, Lanark, Scotland. [Smith, A. J.; Ali, R. R.] UCL, Inst Ophthalmol, Dept Genet, London, England. [Khani, S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Sch Med, Boston, MA USA. RP Li, T (reprint author), NEI, 6 Ctr Dr, Bethesda, MD 20892 USA.; Pawlyk, BS (reprint author), Massachusetts Eye & Ear Infirm, Berman Gund Lab, 243 Charles St, Boston, MA 02114 USA. EM Basil_Pawlyk@meei.harvard.edu; tiansen.li@nih.gov FU National Eye Institute [EY10581]; NEI [5P30EY14104]; Foundation Fighting Blindness; Foundation for Retina Research; Massachusetts Lions Eye Research Fund; European Union (AAVEYE); UK Department of Health, National Institute of Health Research BMRC for Ophthalmology; UK Fight for Sight FX We thank Dr Jeng-Shin Lee at the Research Vector Core at Harvard Medical School for AAV vector packaging, and Drs Peter Colosi and Zhijian Wu at the National Eye Institute for helpful discussions. This work was supported by National Eye Institute grant EY10581, NEI core grant for Vision Research (5P30EY14104), the Foundation Fighting Blindness, the Foundation for Retina Research, the Massachusetts Lions Eye Research Fund and by grants from the European Union (AAVEYE), the UK Department of Health, National Institute of Health Research BMRC for Ophthalmology and UK Fight for Sight. NR 47 TC 4 Z9 4 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD FEB PY 2016 VL 23 IS 2 BP 196 EP 204 DI 10.1038/gt.2015.93 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA DC9NY UT WOS:000369549500010 PM 26348595 ER PT J AU Bregar, AJ Growdon, WB AF Bregar, Amy J. Growdon, Whitfield B. TI Emerging strategies for targeting PI3K in gynecologic cancer SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Gynecologic cancer; PI3K pathway inhibition; mTOR inhibition; Therapeutic resistance ID CLEAR-CELL CARCINOMA; PHASE-II TRIAL; RECURRENT ENDOMETRIAL CARCINOMA; EPITHELIAL OVARIAN-CANCER; UTERINE SEROUS CARCINOMA; ONCOLOGY-GROUP; MAMMALIAN TARGET; HIGH-FREQUENCY; ONCOGENIC MUTATIONS; THERAPEUTIC TARGET AB Ovarian, endometrial and cervical cancers are the most prevalent gynecologic cancers in the United States and account for significant mortality. Translational research into these cancers has highlighted the distinctive molecular and genomic profiles of these cancers finding that, even within a disease site, the landscapes and drivers of neoplasia are distinctive. Despite this molecular diversity, activation of the phosphatidylinositol-3-kinase (PI3K) pathway appears to be conserved in subsets of these tumors, suggesting that strategies that antagonize mediators in this signaling cascade could offer anti-tumor efficacy. Extensive pre-clinical and clinical data have demonstrated that single agent targeted therapies lead to modest single agent activity of generally limited duration, even in the setting of innate PI3K pathway activation via mutation or amplification. These findings in the laboratory and clinic have prompted investigations into resistance pathways following PI3K pathway inhibition in order to understand escape pathways and restore tumor cell sensitivity. A next generation of clinical trial investigations will focus on novel combinations in order to define how these important therapeutics can be used in the clinic. This review will present preclinical data that supports the role of the PI3K pathway in ovarian, endometrial and cervical cancers, in addition to discussing the reported clinical trial experience with PI3K pathway inhibition. A specific focus will be on the rationale behind ongoing clinical trials utilizing novel agents in concert with PI3K pathway inhibitors to reverse resistance in populations with and without gain of function alterations in this oncogenic signaling cascade. (C) 2015 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. RP Growdon, WB (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, THR 901,55 Fruit St, Boston, MA 02114 USA. EM wgrowdon@partners.org NR 120 TC 0 Z9 0 U1 2 U2 10 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 FEB PY 2016 VL 140 IS 2 BP 333 EP 344 DI 10.1016/j.ygyno.2015.09.083 PG 12 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DD1JV UT WOS:000369678900024 PM 26432040 ER PT J AU Miller, SC Mor, V Burgess, JF AF Miller, Susan C. Mor, Vincent Burgess, James F., Jr. TI Studying Nursing Home Innovation: The Green House Model of Nursing Home Care SO HEALTH SERVICES RESEARCH LA English DT Article DE Culture change; person-centered care; nursing homes; innovation ID CULTURE-CHANGE C1 [Miller, Susan C.; Mor, Vincent] Brown Univ, Dept Hlth Serv Policy & Practice, Sch Publ Hlth, 121 South Main St,Room 619, Providence, RI 02912 USA. [Miller, Susan C.; Mor, Vincent] Brown Univ, Ctr Gerontol & Hlth Care Res, Sch Publ Hlth, 121 South Main St,Room 619, Providence, RI 02912 USA. [Burgess, James F., Jr.] Boston Univ, Ctr Healthcare Org & Implementat Res, VA Boston Healthcare Syst, Dept Hlth Law Policy & Management,Sch Publ Hlth, Boston, MA 02215 USA. RP Miller, SC (reprint author), Brown Univ, Dept Hlth Serv Policy & Practice, Sch Publ Hlth, 121 South Main St,Room 619, Providence, RI 02912 USA.; Miller, SC (reprint author), Brown Univ, Ctr Gerontol & Hlth Care Res, Sch Publ Hlth, 121 South Main St,Room 619, Providence, RI 02912 USA. EM susan_miller@brown.edu FU NIA NIH HHS [R01 AG048940] NR 22 TC 0 Z9 0 U1 4 U2 13 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 FEB PY 2016 VL 51 SU 1 BP 335 EP 343 DI 10.1111/1475-6773.12437 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DC9HG UT WOS:000369531300001 PM 26729237 ER PT J AU Sethi, S Anzueto, A Miravitlles, M Arvis, P Alder, J Haverstock, D Trajanovic, M Wilson, R AF Sethi, S. Anzueto, A. Miravitlles, M. Arvis, P. Alder, J. Haverstock, D. Trajanovic, M. Wilson, R. TI Determinants of bacteriological outcomes in exacerbations of chronic obstructive pulmonary disease SO INFECTION LA English DT Article DE Bacteriological outcomes; Beta-lactams; Exacerbation of chronic obstructive pulmonary disease; Fluoroquinolones; Risk factors; Systemic corticosteroids ID CHRONIC-BRONCHITIS; HAEMOPHILUS-INFLUENZAE; CONTROLLED-TRIAL; GENE-EXPRESSION; COPD; MOXIFLOXACIN; INFLAMMATION; ANTIBIOTICS; INFECTIONS; COLONIZATION AB Changes in sputum microbiology following antibiotic treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), including patterns of bacteriological relapse and superinfection are not well understood. Sputum microbiology at exacerbation is not routinely performed, but pathogen presence and species are determinants of outcomes. Therefore, we determined whether baseline clinical factors could predict the presence of bacterial pathogens at exacerbation. Bacterial eradication at end of treatment (EOT) is associated with clinical resolution of exacerbation. We determined the clinical, microbiological and therapeutic factors that were associated with bacteriological eradication in AECOPD at EOT and in the following 8 weeks. Sputum bacteriological outcomes (i.e., eradication, persistence, superinfection, reinfection) from AECOPD patients (N = 1352) who were randomized to receive moxifloxacin or amoxicillin/clavulanate in the MAESTRAL study were compared. Independent predictors of bacterial presence in sputum at exacerbation and determinants for bacteriological eradication were analyzed by logistic regression and receiver operating characteristic (ROC) analyses. Significantly greater bacteriological eradication with moxifloxacin was mainly driven by superior Haemophilus influenzae eradication (P = 0.002, EOT). Baseline clinical factors were a weak predictor of the presence of pathogens in sputum (AUC(ROC) = 0.593). On multivariate analysis, poorer bacterial eradication was associated with antibiotic resistance (P = 0.0001), systemic steroid use (P = 0.0024) and presence of P. aeruginosa (P = 0.0282). Since clinical prediction of bacterial presence in sputum at AECOPD is poor, sputum microbiological analysis should be considered for guiding antibiotic therapy in moderate-to-severe AECOPD, particularly in those who received concomitant systemic corticosteroids or are at risk for infection with antibiotic-resistant bacteria. C1 [Sethi, S.] SUNY Buffalo, Div Pulm Crit Care & Sleep Med, Buffalo, NY 14260 USA. [Sethi, S.] VA Med Res, 151,3495 Bailey Ave, Buffalo, NY 14215 USA. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Miravitlles, M.] Hosp Univ Vall dHebron, Dept Pneumol, CIBER Enfermedades Resp CIBERES, Barcelona, Spain. [Arvis, P.] Bayer HealthCare, Loos, France. [Alder, J.; Haverstock, D.] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Trajanovic, M.] Bayer Inc, Toronto, ON, Canada. [Wilson, R.] Royal Brompton Hosp, Host Def Unit, London SW3 6LY, England. RP Sethi, S (reprint author), SUNY Buffalo, Div Pulm Crit Care & Sleep Med, Buffalo, NY 14260 USA.; Sethi, S (reprint author), VA Med Res, 151,3495 Bailey Ave, Buffalo, NY 14215 USA. EM ssethi@buffalo.edu OI Miravitlles, Marc/0000-0002-9850-9520 FU Bayer HealthCare AG, Germany FX Highfield Communication (Oxford, United Kingdom) provided editorial assistance in preparation of this manuscript. This work was supported by Bayer HealthCare AG, Germany. NR 36 TC 1 Z9 1 U1 0 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0300-8126 EI 1439-0973 J9 INFECTION JI Infection PD FEB PY 2016 VL 44 IS 1 BP 65 EP 76 DI 10.1007/s15010-015-0833-3 PG 12 WC Infectious Diseases SC Infectious Diseases GA DC5ZJ UT WOS:000369299000008 PM 26370552 ER PT J AU Petrou, SP Davidiuk, AJ Rawal, B Arnold, M Thiel, DD AF Petrou, Steven P. Davidiuk, Andrew J. Rawal, Bhupendra Arnold, Michelle Thiel, David D. TI Salvage autologous fascial sling after failed synthetic midurethral sling: Greater than 3-year outcomes SO INTERNATIONAL JOURNAL OF UROLOGY LA English DT Article DE autologous fascial sling; failed midurethral sling; recurrent stress urinary incontinence; repeat sling; salvage fascial sling ID STRESS URINARY-INCONTINENCE; SURGERY; SUCCESS; WOMEN; TAPE AB ObjectiveTo determine long-term surgical outcomes of salvage autologous fascial sling placement after a failed synthetic midurethral sling. MethodsWomen who had undergone autologous fascial sling placement without concomitant pelvic surgery for a failed synthetic midurethral sling utilizing mesh with a minimum follow up of 36 months were identified. Charts were reviewed, and patients were contacted by telephone. Success was determined by the Patient Global Impression of Improvement. Secondary measures included the Incontinence Severity Index questionnaire, patient recommendation of the autologous fascial sling and need for further incontinence surgery. ResultsA total of 35 patients met the criteria, and 21 were successfully contacted. Of those contacted, the median age at surgery was 67 years (range 53-81 years) and at the time of the survey was 75 years (range 63-84 years) with median follow up of 74 months (range 36-127 years). Preoperatively, 12 patients (57.1%) had urethral hypermobility and 13 patients (61.9%) had mixed urinary incontinence. Eight patients (38.1%) had concomitant sling excision with five of those combined with urethrolysis at the time of the salvage operation. Patient Global Impression of Improvement success was noted in 16 patients (76.2%). A total of 11 patients (52.4%) were dry or had slight incontinence by the Incontinence Severity Index. One patient required additional anti-incontinence surgery (4.8%). A total of 18 patients (85.7%) recommended the autologous fascial sling. No statistical impact was noted with sling excision (P = 0.62), mixed urinary incontinence (P = 0.61), age at surgery (P = 0.23), age at follow up (P = 0.15), length of follow up (P = 0.71) or first surgery type (transobturator tape vs retropubic; P = 1.00). ConclusionsAutologous fascial sling provides reasonable long-term success as a salvage operation for failed midurethral slings. C1 [Petrou, Steven P.; Davidiuk, Andrew J.; Thiel, David D.] Mayo Clin, Dept Urol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. [Rawal, Bhupendra] Mayo Clin, Div Biomed Stat & Informat, Jacksonville, FL 32224 USA. [Arnold, Michelle] Mayo Clin, Dept Hlth Sci Res, Jacksonville, FL 32224 USA. [Rawal, Bhupendra] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Petrou, SP (reprint author), Mayo Clin, Dept Urol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM petrou.steven@mayo.edu NR 17 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-8172 EI 1442-2042 J9 INT J UROL JI Int. J. Urol. PD FEB PY 2016 VL 23 IS 2 BP 178 EP 181 DI 10.1111/iju.13003 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA DC3YJ UT WOS:000369155700018 PM 26563492 ER PT J AU Upadhyay, GA Singh, JP AF Upadhyay, Gaurav A. Singh, Jagmeet P. TI Spinal Cord Stimulation for Heart Failure in the DEFEAT-HF Study Lost Battle or Lasting Opportunities? SO JACC-HEART FAILURE LA English DT Editorial Material DE clinical trial results; heart failure; spinal cord stimulation ID INTRACTABLE ANGINA-PECTORIS; VENTRICULAR-ARRHYTHMIAS; MODEL; PAIN; MECHANISMS C1 [Upadhyay, Gaurav A.] Univ Chicago Hosp, Heart Rhythm Ctr, Chicago, IL 60637 USA. [Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Heart Ctr, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@mgh.harvard.edu NR 23 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD FEB PY 2016 VL 4 IS 2 BP 137 EP 139 DI 10.1016/j.jchf.2015.11.007 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DC4LK UT WOS:000369192200007 PM 26746373 ER PT J AU Maher, DP White, PF AF Maher, Dermot P. White, Paul F. TI Proposed mechanisms for association between opioid usage and cancer recurrence after surgery SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material ID CELL LUNG-CANCER; ASSISTED THORACIC-SURGERY; RETROSPECTIVE ANALYSIS; RADICAL PROSTATECTOMY; ANESTHETIC TECHNIQUE; PAIN MANAGEMENT; BREAST-CANCER; TUMOR-GROWTH; INDUCED IMMUNOSUPPRESSION; NEURAXIAL ANALGESIA C1 [Maher, Dermot P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB 444, Boston, MA 02114 USA. [White, Paul F.] Cedars Sinai Med Ctr, Dept Anesthesiol, Los Angeles, CA 90048 USA. [White, Paul F.] Univ Bologna, Inst Ortoped Rizzoli, I-40126 Bologna, Italy. [White, Paul F.] White Mt Inst, The Sea Ranch, CA USA. RP Maher, DP (reprint author), 8700 Beverly Blvd Room 4209, Los Angeles, CA 90048 USA. EM dpmaher@mgh.harvard.edu; paul.white@cshs.org NR 60 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 2016 VL 28 BP 36 EP 40 DI 10.1016/j.jclinane.2015.05.010 PG 5 WC Anesthesiology SC Anesthesiology GA DC4MF UT WOS:000369194300009 PM 26345433 ER PT J AU Zhu, JM Hamel, D Dhaliwal, G Glass, M Sharpe, B Kim, B Monash, B AF Zhu, Jane M. Hamel, David Dhaliwal, Gurpreet Glass, Marcia Sharpe, Bradley Kim, Benjamin Monash, Bradley TI Breakdown SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID HEMOLYTIC-ANEMIA C1 [Zhu, Jane M.; Hamel, David; Dhaliwal, Gurpreet; Glass, Marcia; Sharpe, Bradley; Kim, Benjamin; Monash, Bradley] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Hamel, David; Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Monash, B (reprint author), 533 Parnassus Ave,Box 0131, San Francisco, CA 94143 USA. EM bradley.monash@ucsf.edu NR 9 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2016 VL 11 IS 2 BP 126 EP 129 DI 10.1002/jhm.2530 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DC5VB UT WOS:000369287500008 PM 26800656 ER PT J AU Goode, CJ Ponte, PR Havens, DS AF Goode, Colleen J. Ponte, Patricia Reid Havens, Donna Sullivan TI Residency for Transition Into Practice An Essential Requirement for New Graduates From Basic RN Programs SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID NURSE; TURNOVER; OUTCOMES AB Nurse residency programs have been developed with the goal of helping newly licensed nurses successfully transition to independent practice. The authors propose that all newly licensed nurses hired in acute care hospitals be required to complete an accredited residency program. An evidence table examines the state of the science related to transition-to-practice programs and provides the basis for recommendations. C1 [Goode, Colleen J.] Univ Colorado Denver, Coll Nursing, Healthcare Syst, 13120 E 19th Ave,C288-19, Aurora, CO 80045 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Patient Care Serv, 75 Francis St, Boston, MA 02115 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Dana Farber Canc Inst, Patient Care Serv, 75 Francis St, Boston, MA 02115 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Oncol Nursing & Clin Serv, 75 Francis St, Boston, MA 02115 USA. [Havens, Donna Sullivan] Univ N Carolina, Sch Nursing, Healthcare Syst & Outcomes, Chapel Hill, NC USA. RP Goode, CJ (reprint author), Univ Colorado Denver, Coll Nursing, Healthcare Syst, 13120 E 19th Ave,C288-19, Aurora, CO 80045 USA. EM Colleen.Goode@ucdenver.edu NR 30 TC 3 Z9 3 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD FEB PY 2016 VL 46 IS 2 BP 82 EP 86 DI 10.1097/NNA.0000000000000300 PG 5 WC Nursing SC Nursing GA DC9EV UT WOS:000369524800007 PM 26771476 ER PT J AU Hao, L Huang, KH Ito, K Sae-Tan, S Lambert, JD Ross, AC AF Hao, Lei Huang, Kuan-Hsun Ito, Kyoko Sae-tan, Sudathip Lambert, Joshua D. Ross, A. Catharine TI Fibroblast Growth Factor 21 (Fgf21) Gene Expression Is Elevated in the Liver of Mice Fed a High-Carbohydrate Liquid Diet and Attenuated by a Lipid Emulsion but Is Not Upregulated in the Liver of Mice Fed a High-Fat Obesogenic Diet SO JOURNAL OF NUTRITION LA English DT Article DE fibroblast growth factor; high-carbohydrate diet; high-fat diet; steatosis; exercise ID PPAR-ALPHA; METABOLIC REGULATOR; FIBROBLAST-GROWTH-FACTOR-21; RESTRICTION; EXERCISE; MEDIATOR; FGF-21 AB Background: Fibroblast growth factor 21 (FGF21) is a regulator of carbohydrate and lipid metabolism; however, the regulation of Fgf21 gene expression by diet remains incompletely understood. Objective: We investigated the effect of a high-carbohydrate (HC) liquid diet, with and without supplementation with a lipid emulsion (LE), and of a high-fat diet (HFD) compared with a low-fat diet (LFD) on the regulation of Fgf21 gene expression in the liver of intact mice. Methods: C57BL/6 male mice were fed standard feed pellets (SFPs), a purified HC liquid diet (adequate in calories and protein), or an HC liquid diet containing an LE at either 4% or 13.5% of energy for 5 wk (Expt. 1) or 1 wk (Expt. 2). In Expt. 3, mice were fed a purified LFD (similar to 10% fat) or HFD (similar to 60% fat) or were fed an HFD and given access to a running wheel for voluntary exercise for 16 wk. Results: Fgf21 mRNA in liver and FGF21 protein in plasma were increased by 3.5- to 7-fold in HC mice compared with SFP mice (P < 0.001), whereas the LE dose-dependently attenuated the induction of Fgf21 expression (P < 0.05). After 16 wk, hepatic Fgf21 mRNA did not differ between LFD and HFD mice but was dramatically reduced in the HFD+exercise group to <20% of the level in the HFD group (P < 0.0001). Conclusions: In mice, hepatic Fgf21 expression was upregulated by 1 and 5 wk of feeding a lipogenic HC diet but not by 16 wk of feeding an obesogenic HFD, whereas the addition of fat as an LE to the HC formula significantly reduced Fgf21 gene expression and the plasma FGF21 protein concentration. Our results support a strong and reversible response of hepatic Fgf21 expression to shifts in dietary glucose intake. C1 [Hao, Lei; Huang, Kuan-Hsun; Ito, Kyoko; Ross, A. Catharine] Penn State Univ, Huck Inst Life Sci, Dept Nutr Sci, University Pk, PA 16802 USA. [Sae-tan, Sudathip; Lambert, Joshua D.] Penn State Univ, Dept Food Sci, Huck Inst Life Sci, University Pk, PA 16802 USA. [Ross, A. Catharine] Penn State Univ, Ctr Immunol & Infect Dis, Huck Inst Life Sci, University Pk, PA 16802 USA. [Hao, Lei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Lipid Med & Technol, Charlestown, MA 02129 USA. [Ito, Kyoko] Jikei Univ, Dept Med, Tokyo, Japan. [Sae-tan, Sudathip] Kasetsart Univ, Fac Agroind, Dept Food Sci & Technol, Bangkok, Thailand. RP Ross, AC (reprint author), Penn State Univ, Huck Inst Life Sci, Dept Nutr Sci, University Pk, PA 16802 USA.; Ross, AC (reprint author), Penn State Univ, Ctr Immunol & Infect Dis, Huck Inst Life Sci, University Pk, PA 16802 USA. EM acr6@psu.edu FU Graduate Program in Nutrition, Graduate Program in Food Science, Dorothy Foehr Huck Chair (ACR); NIH [CA90214, AT004678]; Baxter FX Supported by funds from the Graduate Program in Nutrition, Graduate Program in Food Science, Dorothy Foehr Huck Chair (ACR), and NIH grants CA90214 (ACR) and AT004678 (JDL). Baxter Healthcare Corporation provided the liquid diet (Clinimix E), vitamins, and lipid emulsion (Intralipid) used in studies 1 and 2. A postdoctoral research award from Baxter to the Department of Nutritional Sciences partially supported KI. NR 25 TC 1 Z9 1 U1 1 U2 10 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 FEB PY 2016 VL 146 IS 2 BP 184 EP 190 DI 10.3945/jn.115.216572 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DC9RD UT WOS:000369557800002 PM 26764334 ER PT J AU Lerner, DP Tseng, BP Goldstein, LB AF Lerner, David P. Tseng, Bertrand P. Goldstein, Larry B. TI Development and Assessment of a Computer Algorithm for Stroke Vascular Localization Using Components of the National Institutes of Health Stroke Scale SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Ischemic stroke; computer-based model; acute stroke; localization ID CEREBRAL INFARCTION; ISCHEMIC-STROKE; EXPERT SYSTEM; SCORE AB Background: The National Institutes of Health Stroke Scale (NIHSS) was not intended to be used to determine the stroke's vascular distribution. The aim of this study was to develop, assess the reliability, and validate a computer algorithm based on the NIHSS for this purpose. Methods: Two cohorts of patients with ischemic stroke having similar distributions of Oxfordshire localizations (total anterior, partial anterior, lacunar, and posterior circulation) based on neuroimaging were identified. The first cohort (n = 40) was used to develop a computer algorithm for vascular localization using a modified version of the NIHSS (NIHSSLocalization [NIHSS-Loc]) that included the laterality of selected deficits; the second (n = 20) was used to assess the reliability of algorithm-based localizations compared to those of 2 vascular neurologists. The validity of the algorithm-based localizations was assessed in comparison to neuroimaging. Agreement was assessed using the unweighted kappa (kappa) statistic. Results: Agreement between the 2 raters using the standard NIHSS was slight to moderate (kappa =.36, 95% confidence interval [CI] .10-.61). Inter-rater agreement significantly improved to the substantial to almost perfect range using the NIHSS-Loc (kappa=.88, 95% CI .73-1.00). Agreement was perfect when the 2 raters entered the data into the NIHSS-Loc computer algorithm (kappa = 1.00, 95% CI 1.00-1.00). Agreement between the algorithm localization and neuroimaging results was fair to moderate (kappa = .59,95% CI .35-.84) and not significantly different from the localizations of either rater using the NIHSS-Loc. Conclusion: A computerized, modified version of the standard NIHSS can be used to reliably and validly assign the vascular distribution of an acute ischemic stroke. C1 [Lerner, David P.] Massachusetts Gen Hosp, 55 Fruit St,WACC 720, Boston, MA 02114 USA. [Tseng, Bertrand P.] Duke Univ, Med Ctr, Durham, NC USA. [Goldstein, Larry B.] Univ Kentucky, KY Clin, Lexington, KY USA. RP Lerner, DP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WACC 720, Boston, MA 02114 USA. EM dplerner@mgh.harvard.edu NR 17 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD FEB PY 2016 VL 25 IS 2 BP 281 EP 287 DI 10.1016/j.jstrokecerebrovasdis.2015.09.029 PG 7 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DC9YW UT WOS:000369578500013 PM 26542823 ER PT J AU Chebib, I Chang, CY Kerr, DA Deshpande, V Nielsen, GP AF Chebib, Ivan Chang, Connie Y. Kerr, Darcy A. Deshpande, Vikram Nielsen, G. Petur TI Histopathology of So-Called Synovial Cysts of the Lumbar Spine SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Miami, Miller Sch Med, Miami, FL 33136 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 45 BP 15A EP 15A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700046 ER PT J AU Aplin, AC Kohler, T Nicosia, R AF Aplin, Alfred C. Kohler, Ted Nicosia, Roberto TI Human Plaque-Aortic Ring Co-Culture: A Novel Assay for the Study of Atherosclerosis-Induced Angiogenesis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound HCS, Seattle, WA 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 316 BP 81A EP 81A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700317 ER PT J AU Fishbein, GA Onozato, ML Luk, A Givertz, MM Padera, RF Iafrate, AJ Mitchell, RN AF Fishbein, Gregory A. Onozato, Maristela L. Luk, Adriana Givertz, Michael M. Padera, Robert F., Jr. Iafrate, Anthony J. Mitchell, Richard N. TI Endothelial Cell Chimerism in Human Cardiac Allografts SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 320 BP 82A EP 82A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700321 ER PT J AU Mirkovic, J Zhao, LN Faquin, WC Jo, VY Krane, JF AF Mirkovic, Jelena Zhao, Liena Faquin, William C. Jo, Vickie Y. Krane, Jeffrey F. TI Risk-Stratified Triage of Salivary Gland Fine-Needle Aspiration Specimens SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 428 BP 109A EP 110A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700429 ER PT J AU Nagymanyoki, Z Karlon, W Faquin, WC Krane, JF Lindeman, N Hall, D Sweeney, BJ Ljung, BM Balassanian, R van Zante, A AF Nagymanyoki, Zoltan Karlon, William Faquin, William C. Krane, Jeffrey F. Lindeman, Neal Hall, Dimity Sweeney, Brenda J. Ljung, Britt-Marie Balassanian, Ronald van Zante, Annemieke TI Comparison of Molecular Platforms for Detection of HPV in FNA Biopsies of the Head and Neck SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. West Pacific Med Lab, Santa Fe Springs, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 431 BP 110A EP 110A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700432 ER PT J AU Pusztaszeri, M Sadow, PM Krane, JF Daniels, G Faquin, WC AF Pusztaszeri, Marc Sadow, Peter M. Krane, Jeffrey F. Daniels, Gilbert Faquin, William C. TI Fine-Needle Aspiration of Thyroid Malignancies Arising in Disease: A Diagnostic Challenge? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Hosp Geneva, Geneva, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, 75 Francis St, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 441 BP 113A EP 113A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700442 ER PT J AU Rosenbaum, MW Jones, M Dudley, J Le, L Iafrate, AJ Pitman, M AF Rosenbaum, Matthew W. Jones, Martin Dudley, Jonathan Le, Long Iafrate, A. John Pitman, Martha TI Next Generation Sequencing Adds Value to the Pre-Operative Diagnosis of Pancreatic Cysts SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Palo Alto, CA 94304 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 442 BP 113A EP 113A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700443 ER PT J AU Strickland, KC Vivero, M Jo, VY Lowe, A Hollowell, M Qian, X Wieczorek, T French, CA Teot, LA Eszlinger, M Paschke, R Sadow, PM Cibas, E Barletta, JA Krane, JF AF Strickland, Kyle C. Vivero, Marina Jo, Vickie Y. Lowe, Alarice Hollowell, Monica Qian, Xiaohuo Wieczorek, Tad French, Christopher A. Teot, Lisa A. Eszlinger, Markus Paschke, Ralf Sadow, Peter M. Cibas, Edmund Barletta, Justine A. Krane, Jeffrey F. TI The Cytologic Diagnosis of Non-Invasive Follicular Variant of Papillary Thyroid Carcinoma: A Prospective Analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Leipzig, D-04109 Leipzig, Germany. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 458 BP 117A EP 118A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700459 ER PT J AU Wang, H Hoda, RS Faquin, WC Rossi, E Hotchandani, N Sun, T Pusztaszeri, M Bizzarro, T Bongiovanni, M Patel, V Jhala, N Gong, Y AF Wang, He Hoda, Raza S. Faquin, William C. Rossi, Esther Hotchandani, Nihar Sun, Tianlin Pusztaszeri, Marc Bizzarro, Tommaso Bongiovanni, Massimo Patel, Viren Jhala, Nirag Gong, Yun TI Secondary Malignancies in Salivary Glands: A Multi-Institutional FNA Cohort from Trans-Atlantic Academic Institutions SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cattolica Sacro Cuore, Rome, Italy. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Hosp Geneva, Geneva, Switzerland. Univ Lausanne, Lausanne, Switzerland. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 468 BP 120A EP 120A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700469 ER PT J AU Moy, A Murali, M Kroshinsky, D Horn, T Nazarian, R AF Moy, Andrea Murali, Mandakolathur Kroshinsky, Daniela Horn, Thomas Nazarian, Rosalynn TI Keratin 17 Expression and Immune Phenotype of Anti-TNF-alpha Refractory Psoriasis and Anti-TNF-alpha Related Psoriasiform Dermatitis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Moy, Andrea; Murali, Mandakolathur; Kroshinsky, Daniela; Horn, Thomas; Nazarian, Rosalynn] 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 519 BP 133A EP 133A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700520 ER PT J AU Glomski, K Sadow, PM AF Glomski, Krzysztof Sadow, Peter M. TI Metastatic Follicular Thyroid Carcinoma: Retrospective Institutional Experience and Insight into Primary Follicular Thyroid Neoplasia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 579 BP 148A EP 148A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700580 ER PT J AU Paulson, V Shivdasani, P Howitt, BE Ducar, M Angell, T Alexander, EK Cibas, E Krane, JF Lindeman, N Barletta, JA AF Paulson, Vera Shivdasani, Priyanka Howitt, Brooke E. Ducar, Matthew Angell, Trevor Alexander, Erik K. Cibas, Edmund Krane, Jeffrey F. Lindeman, Neal Barletta, Justine A. TI Non-Invasive Follicular Variant of Papillary Thyroid Carcinoma Accounts for over Half of Carcinomas Harboring RAS Mutations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 599 BP 153A EP 153A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270700600 ER PT J AU Agoston, A Deshpande, V Odze, R AF Agoston, Agoston Deshpande, Vikram Odze, Robert TI HPV is Not Involved in the Pathogenesis of Esophageal Squamous Cell and Adenocarcinomas; Analysis Based on a Highly Sensitive and Highly Specific RNA In-Situ Hybridization Technique SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 626 BP 160A EP 160A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701009 ER PT J AU Ahn, S Lee, SJ Kim, YG Hwang, CS Kim, A Shin, N Choi, KU Lee, CH Huh, GY Lauwers, GY Park, DY AF Ahn, Sangjeong Lee, So Jeong Kim, Young Geum Hwang, Chung Su Kim, Ahrong Shin, Nari Choi, Kyung Un Lee, Chang Hun Huh, Gi Young Lauwers, Gregory Y. Park, Do Youn TI Molecular Classification in Gastric Cancer Using Immunohistochemistry SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Pusan Natl Univ, Sch Med, Pusan Natl Univ Hosp, Busan, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 627 BP 160A EP 160A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701010 ER PT J AU Alpert, L Setia, N Khalili, H Lauwers, GY AF Alpert, Lindsay Setia, Namrata Khalili, Hamed Lauwers, Gregory Y. TI Lymphocytic Colitis: Are There Pathologic Predictors of Response to Therapy? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Chicago, Chicago, IL 60637 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 633 BP 161A EP 161A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701016 ER PT J AU Deshpande, V Mahadevan, KK Lauwers, GY Mattia, A Zukerberg, L Odze, R AF Deshpande, Vikram Mahadevan, Krishnan K. Lauwers, Gregory Y. Mattia, Antony Zukerberg, Lawrence Odze, Robert TI LGR5 Expression in Barrett's Esophagus and Associated Neoplasia: Support for Its Role as a Cancer Stem Cell and Diagnostic Marker SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Deshpande, Vikram; Mahadevan, Krishnan K.; Lauwers, Gregory Y.; Mattia, Antony; Zukerberg, Lawrence; Odze, Robert] Brigham & Womens Hosp, Massachusetts Gen Hosp, 75 Francis St, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 667 BP 169A EP 169A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701050 ER PT J AU England, J Swager, AF Schlachter, S Sundell, B Bergman, JJGHM Lauwers, GY Odze, R AF England, Jonathan Swager, Anne-Fre Schlachter, Simon Sundell, Brian Bergman, Jacques J. G. H. M. Lauwers, Gregory Y. Odze, Robert TI Role of Mucosal Glands in the Progression of Neoplasia in Barrett's Esophagus SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NinePoint Med, Boston, MA USA. Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 672 BP 170A EP 170A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701055 ER PT J AU Samore, W Mahadevan, KK Deshpande, V AF Samore, Wesley Mahadevan, Krishnan K. Deshpande, Vikram TI Line-1 Methylation Status Predicts Aggressive Behavior in Pancreatic Endocrine Neoplasms SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Samore, Wesley; Mahadevan, Krishnan K.; Deshpande, Vikram] 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 782 BP 197A EP 197A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701165 ER PT J AU Setia, N Alpert, L Lauwers, GY AF Setia, Namrata Alpert, Lindsay Lauwers, Gregory Y. TI WHO Morphologic Classification of Gastric Cancer Correlates with Protein Expression Based Classification SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Chicago, Chicago, IL 60637 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 792 BP 199A EP 200A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701175 ER PT J AU Shih, AR Bal, M Zukerberg, L Brown, I Lauwers, GY Liu, XL Kelly, P Oliva, E Ahn, S Kim, K Deshpande, V AF Shih, Angela R. Bal, Munita Zukerberg, Lawrence Brown, Ian Lauwers, Gregory Y. Liu, Xiuli Kelly, Paul Oliva, Esther Ahn, Soomin Kim, Kyoung Deshpande, Vikram TI Hepatoid Carcinomas of the Gastrointestinal Tract: A Reappraisal of Morphological and Immunohistochemical Features SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tata Mem Hosp, Bombay 400012, Maharashtra, India. Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. Cleveland Clin, Cleveland, OH 44106 USA. Queens Univ Belfast, Royal Victoria Hosp, Belfast, Antrim, North Ireland. Sungkyunkwan Univ, Samsung Med Ctr, Seoul, South Korea. RI Brown, Ian/R-7763-2016 OI Brown, Ian/0000-0001-6329-2547 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 796 BP 200A EP 201A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701179 ER PT J AU Shih, AR Deshpande, V Ferry, JA Zukerberg, L AF Shih, Angela R. Deshpande, Vikram Ferry, Judith A. Zukerberg, Lawrence TI Clinicopathologic Characteristics of Systemic Mastocytosis in the Intestine SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Shih, Angela R.; Deshpande, Vikram; Ferry, Judith A.; Zukerberg, Lawrence] Massachusetts Gen Hosp, Boston, MA 02114 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 797 BP 201A EP 201A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701180 ER PT J AU Williams, E Zukerberg, L Arora, K Ting, DT Deshpande, V AF Williams, Erik Zukerberg, Lawrence Arora, Kshitij Ting, David T. Deshpande, Vikram TI Epithelial to Mesenchymal Transition Predicts Distant Metastasis in MMR-Intact Colonic Adenocarcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Williams, Erik; Zukerberg, Lawrence; Arora, Kshitij; Ting, David T.; Deshpande, Vikram] 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 821 BP 207A EP 207A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701204 ER PT J AU Yilmaz, O Agrawal, T Kantekure, K Suarez, Y Yilmaz, O Deshpande, V AF Yilmaz, Osman Agrawal, Tanupriya Kantekure, Kanchan Suarez, Yvelisse Yilmaz, Omer Deshpande, Vikram TI WNT Signaling Markers, LGR5 and AXIN2, Show Unique Patterns of Expression in Colonic Polyps SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Med Ctr, Boston, MA USA. MIT, 77 Massachusetts Ave, Cambridge, MA 02139 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 831 BP 209A EP 210A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701214 ER PT J AU Cyrta, J Beltran, H Prandi, D Mosquera, JM Benelli, M Tomlins, SA Elemento, O Sboner, A Garraway, L Rubin, M Demichelis, F AF Cyrta, Joanna Beltran, Himisha Prandi, Davide Mosquera, Juan Miguel Benelli, Matteo Tomlins, Scott A. Elemento, Olivier Sboner, Andrea Garraway, Levi Rubin, Mark Demichelis, Francesca TI Integrated Molecular Classifier Determines Transdifferentiation to Neuroendocrine Prostate Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Cornell Univ, Weill Cornell Med, New York, NY 10021 USA. Univ Trento, Trento, Italy. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 889 BP 224A EP 224A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701272 ER PT J AU Udager, A Chinnaiyan, AM Petimar, J Cao, XH Feng, FY Loda, M Ahearn, T Kantoff, PW Mucci, LA Mehra, R AF Udager, Aaron Chinnaiyan, Arul M. Petimar, Joshua Cao, Xuhong Feng, Felix Y. Loda, Massimo Ahearn, Thomas Kantoff, Philip W. Mucci, Lorelei A. Mehra, Rohit TI Overexpression of the Long Non-Coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Michigan Hlth Syst, Ann Arbor, MI USA. Michigan Ctr Translat Pathol, Ann Arbor, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1065 BP 268A EP 268A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701448 ER PT J AU Ye, HH Sowalsky, AG Schaefer, R Yuan, X Chen, SY Gerrin, SJ Montaser, L Ma, F Voznesensky, O Cai, CM Lis, R Zhang, ZW Loda, M Taplin, ME Balk, S AF Ye, Huihui Sowalsky, Adam G. Schaefer, Rachel Yuan, Xin Chen, Shao-Yong Gerrin, Sean J. Montaser, Laleh Ma, Fen Voznesensky, Olga Cai, Changmeng Lis, Rosina Zhang, Zhenwei Loda, Massimo Taplin, Mary-Ellen Balk, Steven TI Diversity of Resistance Mechanisms in Prostate Cancer after Neoadjuvant Intense Androgen Deprivation Therapy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1078 BP 271A EP 271A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701461 ER PT J AU Basnet, KM Bentley-Lewis, R Wexler, D Kilic, F Roberts, D AF Basnet, Kristen M. Bentley-Lewis, Rhonda Wexler, Deborah Kilic, Fusun Roberts, Drucilla TI Intervillous Thrombi Are Increased in Placentas from Pregnancies Complicated by Diabetes SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1096 BP 276A EP 276A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701478 ER PT J AU Goh, R Dal Cin, P Chiang, S Young, RH Oliva, E AF Goh, Ronald Dal Cin, Paola Chiang, Sarah Young, Robert H. Oliva, Esther TI Myxoid Smooth Muscle Tumors of the Uterus: Clinicopathologic Study of 40 Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Singapore Gen Hosp, Singapore, Singapore. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1133 BP 285A EP 285A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701515 ER PT J AU Harrison, B Chen, A Toledo, G Arora, K Deshpande, V Oliva, E AF Harrison, Beth Chen, Athena Toledo, Gemma Arora, Kshitij Deshpande, Vikram Oliva, Esther TI The MELF Pattern of Myometrial Invasion in Endometrial Endometrioid Carcinoma Displays a Mesenchymal Gene Expression Signature: A Case Series SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Harrison, Beth; Chen, Athena; Toledo, Gemma; Arora, Kshitij; Deshpande, Vikram; Oliva, Esther] 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1135 BP 285A EP 285A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701517 ER PT J AU Howitt, BE Sun, H Roemer, MGM Kelly, A Chapuy, B Aviki, EM Pak, C Gjini, E Yang, YL Lee, L Viswanathan, A Horowitz, N Neuberg, D Crum, CP Lindeman, N Kuo, F Ligon, AH Freeman, GJ Hodi, FS Shipp, MA Rodig, S AF Howitt, Brooke E. Sun, Heather Roemer, Margaretha G. M. Kelly, Alyssa Chapuy, Bjoern Aviki, Emeline M. Pak, Christine Gjini, Evisa Yang, Youling Lee, Larissa Viswanathan, Akila Horowitz, Neil Neuberg, Donna Crum, Christopher P. Lindeman, Neal Kuo, Frank Ligon, Azra H. Freeman, Gordon J. Hodi, F. Stephen Shipp, Margaret A. Rodig, Scott TI Recurrent Gains of CD274 and PDCD1LG2 in Squamous Cell Carcinomas of Cervix and Vulva SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1144 BP 287A EP 288A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701526 ER PT J AU Ordulu, Z McDonald, AG De Nictolis, M Garcia-Fernandez, E Hardisson, D Prat, J Oliva, E AF Ordulu, Zehra McDonald, Anna G. De Nictolis, Michele Garcia-Fernandez, Eugenia Hardisson, David Prat, Jaime Oliva, Esther TI Intravenous Leiomyomatosis (IVL), from Molecular Genetics to Clinical Biomarkers: A Study of 26 Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. San Salvatore Hosp, Pesaro, Italy. Hosp Univ La Paz, Madrid, Spain. Wake Forest Baptist Med Ctr, Winston Salem, NC USA. Hosp Sta Creu & St Pau, Barcelona, Spain. RI Hardisson, David/E-2832-2010 OI Hardisson, David/0000-0002-2183-3699 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1195 BP 300A EP 301A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701577 ER PT J AU Parkash, V Malpica, A Matias-Guiu, X Oliva, E McCluggage, WG AF Parkash, Vinita Malpica, Anais Matias-Guiu, Xavier Oliva, Esther McCluggage, W. Glenn TI Current Practices in the Processing, Diagnosis and Reporting of Endometrial Carcinoma. Results of a Web Based Survey by the International Society of Gynecological Pathologists (ISGyP) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Yale Univ, Sch Med, Bridgeport Hosp, New Haven, CT USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Lleida, Hosp Univ Arnau de Vilanova, IRBLleida, Lleida, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1199 BP 301A EP 302A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701581 ER PT J AU Pesci, A Shih, AR Oliva, E AF Pesci, Anna Shih, Angela R. Oliva, Esther TI Endocervical Adenocarcinoma (EEC): A Retrospective Study of 75 Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Osped Sacro Cuore Don Calabria, Verona, Italy. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1201 BP 302A EP 302A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701583 ER PT J AU Pires-Luis, AS Bartosch, C Meireles, C Pinto, C Lopes, JM Shannon, KM Teixeira, MR Oliva, E AF Pires-Luis, Ana S. Bartosch, Carla Meireles, Catarina Pinto, Carla Lopes, Jose M. Shannon, Kristen M. Teixeira, Manuel R. Oliva, Esther TI Hysterectomy Specimens of Patients with Lynch Syndrome: Clinicopathologic Study of 70 Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 IPO Porto, Oporto, Portugal. CHSJ, Oporto, Portugal. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Teixeira, Manuel/E-4885-2011 OI Teixeira, Manuel/0000-0002-4896-5982 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1203 BP 302A EP 303A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701585 ER PT J AU Shih, AR Liu, XL Silva, A Pesci, A Soslow, R Deshpande, V Oliva, E AF Shih, Angela R. Liu, Xiuli Silva, Annacarolina Pesci, Anna Soslow, Robert Deshpande, Vikram Oliva, Esther TI Refined Characterization of Hepatoid Differentiation in Gynecologic Tract Neoplasms SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin, Cleveland, OH 44106 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1227 BP 309A EP 309A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701609 ER PT J AU Silva, A Bennett, JA Ali-Fehmi, R Bandyopadhyay, S Oliva, E AF Silva, Annacarolina Bennett, Jennifer A. Ali-Fehmi, Rouba Bandyopadhyay, Sudeshna Oliva, Esther TI Ovarian Endometrioid Adenocarcinomas: Morphology, Associations and Outcomes in 79 Patients SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Lahey Hosp & Med Ctr, Burlington, MA USA. Wayne State Univ, Detroit, MI USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1228 BP 309A EP 309A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270701610 ER PT J AU Pusztaszeri, M Bordignon, P McKee, T Faquin, WC AF Pusztaszeri, Marc Bordignon, Patrizia McKee, Thomas Faquin, William C. TI MYC and MYB Are Coexpressed in Adenoid Cystic Carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Hosp Geneva, Geneva, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1302 BP 327A EP 328A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702043 ER PT J AU Sajed, D Wu, CL Nose, V Deshpande, V AF Sajed, Dipti Wu, Chin-Lee Nose, Vania Deshpande, Vikram TI Expression of an Androgen Receptor Splice Variant in Salivary Duct Carcinoma: An Instrument of Resistance? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Sajed, Dipti; Wu, Chin-Lee; Nose, Vania; Deshpande, Vikram] 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1306 BP 328A EP 329A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702047 ER PT J AU Ahn, J Rosado, FG Sohani, AR Vos, J AF Ahn, Janice Rosado, Flavia G. Sohani, Aliyah R. Vos, Jeffrey TI Plasmablastic Lymphoma: Characterization of Tumor Microenvironment by CD163 and PD1 Immunohistochemistry SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 W Virginia Univ, Morgantown, WV 26506 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1325 BP 333A EP 333A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702066 ER PT J AU Bledsoe, J Redd, R Zukerberg, L Abramson, J Sohani, AR AF Bledsoe, Jacob Redd, Robert Zukerberg, Lawrence Abramson, Jeremy Sohani, Aliyah R. TI PDL1 and MUM1 Expression Are Associated with Outcome in Primary Mediastinal Large B-cell Lymphoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1337 BP 336A EP 337A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702078 ER PT J AU Bledsoe, J Wallace, ZS Stone, JH Deshpande, V Ferry, JA AF Bledsoe, Jacob Wallace, Zachary S. Stone, John H. Deshpande, Vikram Ferry, Judith A. TI Lymphoma in IgG4-Related Disease SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Bledsoe, Jacob; Wallace, Zachary S.; Stone, John H.; Deshpande, Vikram; Ferry, Judith A.] Massachusetts Gen Hosp, Boston, MA 02114 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1336 BP 336A EP 336A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702077 ER PT J AU Griffin, GK Lovitch, SB Kelley, A Roemer, MGM Chapuy, B Pak, C Gjini, E Freeman, GJ Hodi, FS Ligon, AH Shipp, MA Rodig, S AF Griffin, Gabriel K. Lovitch, Scott B. Kelley, Alyssa Roemer, Margaretha G. M. Chapuy, Bjoern Pak, Christine Gjini, Evisa Freeman, Gordon J. Hodi, F. Stephen Ligon, Azra H. Shipp, Margaret A. Rodig, Scott TI Copy Number Gain of PD-L1 and PD-L2 in T-Cell/Histiocyte Rich Large B-Cell Lymphoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1379 BP 348A EP 348A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702120 ER PT J AU Hillen, L Zukerberg, L Deshpande, V Cleven, AHG Fathi, AT Zur Hausen, A Hasserjian, RP AF Hillen, Lisa Zukerberg, Lawrence Deshpande, Vikram Cleven, Arjen H. G. Fathi, Amir T. Zur Hausen, Axel Hasserjian, Robert P. TI Bone Marrow Morphology Predicts Response to Hypomethylating Agents SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Maastricht Univ, Med Ctr, NL-6200 MD Maastricht, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. Leiden Univ, Med Ctr, Leiden, Netherlands. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1387 BP 350A EP 350A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702128 ER PT J AU Margolskee, E Oak, J Arber, DA Hasserjian, RP Orazi, A AF Margolskee, Elizabeth Oak, Jean Arber, Daniel A. Hasserjian, Robert P. Orazi, Attilio TI Myelodysplastic Syndrome, Unclassifiable (MDS-U) with 1% Blasts Is a Distinct Subgroup of MDS-U with a Poor Prognosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Weill Cornell Med Coll, New York, NY USA. Stanford Univ, Stanford, CA 94305 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1427 BP 361A EP 361A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702167 ER PT J AU Minkovsky, A Morgan, EA Charest, K Schmidt, R Briggs, D Li, B Pozdnyakova, O AF Minkovsky, Alissa Morgan, Elizabeth A. Charest, Karry Schmidt, Ryan Briggs, Debra Li, Betty Pozdnyakova, Olga TI Peripheral Blood Minimal Residual Disease Analysis by Flow Cytometry Has High Concordance with Bone Marrow Analysis for Adult Patients with Acute Lymphoblastic Leukemia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1433 BP 362A EP 363A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702173 ER PT J AU Pozdnyakova, O Aster, JC Kuo, F Brown, R Baltay, M Hasserjian, RP AF Pozdnyakova, Olga Aster, Jon C. Kuo, Frank Brown, Ronald Baltay, Michele Hasserjian, Robert P. TI Primary Myelofibrosis Displays an Inflammation-Associated Gene Profile Distinct from Polycythemia Vera and Essential Thrombocythemia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1462 BP 370A EP 371A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702202 ER PT J AU Rogers, HJ Hsi, ED Tang, GL Wang, S Bueso-Ramos, CE Lubin, D Morrissette, JJD Bagg, A Cherukuri, DP George, TI Peterson, L Liu, YC Mathew, S Orazi, A Hasserjian, RP AF Rogers, Heesun J. Hsi, Eric D. Tang, Guilin Wang, Sa Bueso-Ramos, Carlos E. Lubin, Daniel Morrissette, Jennifer J. D. Bagg, Adam Cherukuri, Durga P. George, Tracy I. Peterson, Loann Liu, Yen-Chun Mathew, Susan Orazi, Attilio Hasserjian, Robert P. TI Most Myeloid Neoplasms with Deletion of Chromosome 16q Are Distinct from Acute Myeloid Leukemia with inv(16)(p13.1q22) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Cleveland Clin, Cleveland, OH 44106 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Northwestern Univ, Chicago, IL 60611 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1473 BP 373A EP 373A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702213 ER PT J AU Weinberg, OK Hasserjian, RP Li, B Pozdnyakova, O AF Weinberg, Olga K. Hasserjian, Robert P. Li, Betty Pozdnyakova, Olga TI Assessment of Myeloid And Monocytic Dysplasia by Flow Cytometry in De Novo AML Helps Define an AML with Myelodysplasia-Related Changes Category SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Boston Childrens Hosp, Boston, MA USA. Massachussets Gen Hosp, Boston, MA USA. Brigham & Womens Hosp, 75 Francis St, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1512 BP 383A EP 383A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702251 ER PT J AU Wertheim, G Luskin, M Gimotty, PA Smith, C Loren, AW Figueroa, M Harrison, J Sun, ZX Tallman, MS Paietta, EM Litzow, MR Levine, R Melnick, AM Fernandez, HF Luger, SM Carroll, M Master, SR AF Wertheim, Gerald Luskin, Marlise Gimotty, Phyllis A. Smith, Catherine Loren, Alison W. Figueroa, Maria Harrison, Jenna Sun, Zhuoxin Tallman, Martin S. Paietta, Elisabeth M. Litzow, Mark R. Levine, Ross Melnick, Ari M. Fernandez, Hugo F. Luger, Selina M. Carroll, Martin Master, Stephen R. TI Integration of Multi-Locus DNA Methylation and Genetic Alterations Outperforms Genetic Assessment Alone for Outcome Prediction in Adult Patients with Acute Myeloid Leukemia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. Mayo Clin, Rochester, MN USA. Moffit Canc Ctr, Tampa, FL USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1514 BP 384A EP 384A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702253 ER PT J AU Wong, WH Hasserjian, RP Pozdnyakova, O AF Wong, Waihay Hasserjian, Robert P. Pozdnyakova, Olga TI Mutational Status Correlates with Distinct Histologic Features in Philadelphia Chromosome (Ph)-Negative Myeloproliferative Neoplasms (MPN) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1516 BP 384A EP 384A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702255 ER PT J AU Tse, JY Deshpande, V Ferry, JA Zukerberg, L AF Tse, Julie Y. Deshpande, Vikram Ferry, Judith A. Zukerberg, Lawrence TI Histopathologic Features of T. Pallidum Infection Differ between the Rectum and Anus SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Tse, Julie Y.; Deshpande, Vikram; Ferry, Judith A.; Zukerberg, Lawrence] 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1546 BP 391A EP 391A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702285 ER PT J AU Adam, B Smith, RN Kawai, T Cosimi, AB Colvin, RB Mengel, M AF Adam, Benjamin Smith, R. Neal Kawai, Tatsuo Cosimi, A. Benedict Colvin, Robert B. Mengel, Michael TI mRNA Diagnosis of Antibody-Mediated Rejection from Routine Paraffin Sections of Renal Transplant Biopsies in a Nonhuman Primate Model SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Alberta, Edmonton, AB, Canada. Harvard Univ, Sch Med, Boston, MA USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1585 BP 402A EP 402A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702324 ER PT J AU Zhou, DL Pozdnyakova, O Dewar, R Hasserjian, RP Etman, A Hoffman, R Salama, ME AF Zhou, Delu Pozdnyakova, Olga Dewar, Rajan Hasserjian, Robert P. Etman, Ali Hoffman, Ronald Salama, Mohamed E. TI Central Histopathology Review of Essential Thrombocythemia and Polycythemia Vera Bone Marrow Biopsies via Digital Tools in a Clinical Trial on Pegylated Interferon Alfa-2a SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Utah, Salt Lake City, UT USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Sch Med, New York, NY 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1584 BP 402A EP 402A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702323 ER PT J AU Faulkner-Jones, BE Rosen, D Rosen, S Harrington, K Law, C AF Faulkner-Jones, Beverly E. Rosen, Devin Rosen, Seymour Harrington, Kyle Law, Charles TI Maximizing Information from the Renal Biopsy: Computer-Generated Three-Dimensional Constructs SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 BIDMC, Boston, MA USA. Kitware Inc, Clifton Pk, NY USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1599 BP 405A EP 405A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702337 ER PT J AU Agrawal, T Yilmaz, O Masia, R Goyal, L Zhu, A Deshpande, V AF Agrawal, Tanupriya Yilmaz, Osman Masia, Ricard Goyal, Lipika Zhu, Andrew Deshpande, Vikram TI Distinctive Morphologic Pattern and In Situ Hybridization for Albumin Distinguishes Intrahepatic Cholangiocarcinoma from Metastatic Adenocarcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Tufts Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 8 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1630 BP 413A EP 413A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702368 ER PT J AU Miller, MB Mir, S Guleria, I Chi, JH Berkowitz, AL Ligon, KL AF Miller, Michael B. Mir, Saad Guleria, Indira Chi, John H. Berkowitz, Aaron L. Ligon, Keith L. TI Tumor-like Mass Arising as a Side Effect of Intrathecal Therapeutic Stem Cell Injections SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1720 BP 434A EP 434A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702458 ER PT J AU Gupta, R Mahadevan, KK Ferrone, CR Ting, DT Deshpande, V AF Gupta, Rajib Mahadevan, Krishnan K. Ferrone, Cristina R. Ting, David T. Deshpande, Vikram TI Quasimesenchymal Phenotype Predicts Distant Metastasis in Pancreatic Ductal Adenocarcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1747 BP 441A EP 441A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702485 ER PT J AU Lennerz, JK Wang, CI Doyle, L Huynh, TG Lindeman, N Srivastava, A Fernandez del-Castillo, C Mino-Kenudson, M AF Lennerz, Jochen K. Wang, Charlotte I. Doyle, Leona Huynh, Tiffany G. Lindeman, Neal Srivastava, Amitabh Fernandez del-Castillo, Carlos Mino-Kenudson, Mari TI Mutational Profiling of Oncocytic Intraductal Papillary Mucinous Neoplasms (IPMN-o) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, 75 Francis St, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1757 BP 443A EP 443A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702495 ER PT J AU Taylor, M Sajed, D Williams, E Ting, DT Deshpande, V AF Taylor, Martin Sajed, Dipti Williams, Erik Ting, David T. Deshpande, Vikram TI LINE-1 RNA and ORF1p Protein Are Broadly Co-Expressed in Colon Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1821 BP 460A EP 460A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270702559 ER PT J AU Huynh, TG Gainor, JF Nardi, V Mino-Kenudson, M AF Huynh, Tiffany G. Gainor, Justin F. Nardi, Valentina Mino-Kenudson, Mari TI Lung Adenocarcinomas with KRAS Mutations Are Biologically Heterogeneous SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Huynh, Tiffany G.; Gainor, Justin F.; Nardi, Valentina; Mino-Kenudson, Mari] 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1871 BP 472A EP 472A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270703023 ER PT J AU Matsubara, O Jin, Y Yamauchi, S Yamanaka, K Ishikawa, Y Mark, EJ AF Matsubara, Osamu Jin, Yasuto Yamauchi, Shuta Yamanaka, Kazuteru Ishikawa, Yuichi Mark, Eugene J. TI Programmed Death 1 (PD-1) and PD-L1 Expression in Lung Adenocarcinoma, with Lower Expression in In Situ and Minimally Invasive Tumors and Higher Expression in Larger and Invasive Tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Japanese Fdn Canc Res, Inst Canc, Tokyo 170, Japan. Hiratsuka Kyosai Hosp, Hiratsuka, Kanagawa, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1888 BP 476A EP 476A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270703040 ER PT J AU Pal, P Hammerman, P Kwiatkowski, DJ Johnson, BE Sholl, LM AF Pal, Prodipto Hammerman, Peter Kwiatkowski, David J. Johnson, Bruce E. Sholl, Lynette M. TI ROS1 Immunohistochemistry as a Screen for ROS1 Rearrangements in Lung Adenocarcinoma: Application in Clinical Practice SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1900 BP 478A EP 478A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270703052 ER PT J AU Redig, AJ Lydon, C Janne, PA Sholl, LM AF Redig, Amanda J. Lydon, Christine Janne, Pasi A. Sholl, Lynette M. TI Evaluation of Genomic Complexity in Next-Generation Sequencing of T1 vs Stage IV Non-Small Cell Lung Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, 75 Francis St, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1909 BP 480A EP 480A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270703061 ER PT J AU Shih, AR Muzikansky, A Bozkurtlar, E Chung, JH Minami, Y Hariri, LP Moreira, A Uruga, H Wang, H Yoshizawa, A Mino-Kenudson, M AF Shih, Angela R. Muzikansky, Alona Bozkurtlar, Emine Chung, Jin-Haeng Minami, Yuko Hariri, Lida P. Moreira, Andre Uruga, Hironori Wang, He Yoshizawa, Akihiko Mino-Kenudson, Mari TI Reproducibility in Classification of Small Lung Adenocarcinomas: An International Interobserver Study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Marmara Univ, Istanbul, Turkey. Seoul Natl Univ, Bundang Hosp, Songnam, South Korea. Ibarakihigashi Natl Hosp, Natl Hosp Org, Naka, Ibaraki, Japan. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. Kyoto Univ Hosp, Kyoto 606, Japan. 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1920 BP 483A EP 483A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270703072 ER PT J AU Sholl, LM Pal, P Alden, RS Feeney, N Paweletz, C Sacher, A Oxnard, GR AF Sholl, Lynette M. Pal, Prodipto Alden, Ryan S. Feeney, Nora Paweletz, Cloud Sacher, Adrian Oxnard, Geoffrey R. TI Predictors of High Levels of Mutant cfDNA in Plasma from Patients with Advanced Lung Adenocarcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Belfer Ctr Appl Canc Sci, Boston, MA USA. RI Sacher, Adrian/I-8080-2016 OI Sacher, Adrian/0000-0001-7865-2701 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1922 BP 483A EP 483A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270703074 ER PT J AU Huck, A Hong, C DeLelys, ME Preffer, FI Sohani, AR AF Huck, Amelia Hong, Christine DeLelys, Michelle E. Preffer, Frederic I. Sohani, Aliyah R. TI A Triaging Strategy Using Absolute White Blood Cell Differential Counts and Smear Morphology Improves Diagnostic Yield of Peripheral Blood Flow Cytometry SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 St Barnabas Hosp, Livingston, NJ USA. Harvard Univ, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 1974 BP 496A EP 496A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270703126 ER PT J AU Guilmette, J Faquin, WC Nielsen, GP Selig, M Nose, V Sadow, PM AF Guilmette, Julie Faquin, William C. Nielsen, G. Petur Selig, Martin Nose, Vania Sadow, Peter M. TI Is Mammary Analogue Secretory Carcinoma of the Salivary Glands a Distinct Entity from Acinic Cell Carcinoma: An Ultrastructural Study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Montreal, Med Ctr, Montreal, PQ, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2016 VL 96 SU 1 MA 2041 BP 514A EP 514A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DC5OQ UT WOS:000369270703193 ER PT J AU Nazha, A Sekeres, MA Garcia-Manero, G Barnard, J Al Ali, NH Roboz, GJ Steensma, DP DeZern, AE Zimmerman, C Jabbour, EJ Zell, K List, AF Kantarjian, HM Maciejewski, JP Komrokji, RS AF Nazha, Aziz Sekeres, Mikkael A. Garcia-Manero, Guillermo Barnard, John Al Ali, Najla H. Roboz, Gail J. Steensma, David P. DeZern, Amy E. Zimmerman, Cassie Jabbour, Elias J. Zell, Katrina List, Alan F. Kantarjian, Hagop M. Maciejewski, Jaroslaw P. Komrokji, Rami S. CA MDS Clinical Res Consortium TI Outcomes of patients with myelodysplastic syndromes who achieve stable disease after treatment with hypomethylating agents SO LEUKEMIA RESEARCH LA English DT Article DE MDS; Response; Stable disease; Hypomethylating agent ID CONVENTIONAL CARE REGIMENS; PHASE-III; LEUKEMIA GROUP; AZACITIDINE; DECITABINE; CANCER; TRIAL AB Treatment with hypomethylating agents (HMAs) improves overall survival (OS) in patients who achieve a response of stable disease (SD) or better (complete remission [CR], partial remission [PR], or hematologic improvement [HI]). It is not well established if patients who achieve SD at 4-6 months of therapy should be offered different therapies to optimize their response or continue with the same regimen. Clinical data were obtained from the MDS Clinical Research Consortium database. SD was defined as no evidence of progression and without achievement of any other responses. Of 291 patients treated with AZA or DAC, 55% achieved their best response (BR) at 4-6 months. Among patients with SD at 4-6 months, 29 (20%) achieved a better response at a later treatment time point. Younger patients with lower bone marrow blast percentages, and intermediate risk per IPSS-R were more likely to achieve a better response (CR, PR, or HI) after SD at 4-6 months. Patients with SD who subsequently achieved CR had superior OS compared to patients who remained with SD (28.1 vs. 14.4 months, respectively, p =.04). In conclusion, patients treated with HMAs who achieves CR after a SD status had longer survival with continuous treatment after 6 months. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Nazha, Aziz; Sekeres, Mikkael A.; Zimmerman, Cassie; Maciejewski, Jaroslaw P.] Cleveland Clin, Leukemia Program, Taussig Canc Inst, Cleveland, OH 44106 USA. [Garcia-Manero, Guillermo; Jabbour, Elias J.; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Barnard, John; Zell, Katrina] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Al Ali, Najla H.; List, Alan F.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA. [Roboz, Gail J.] New York Presbyterian Hosp, Weill Cornell Med Coll, Div Hematol & Oncol, New York, NY USA. [Steensma, David P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [DeZern, Amy E.] Johns Hopkins Univ, Sch Med, Div Hematol Malignancies Oncol, Baltimore, MD USA. RP Komrokji, RS (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hematol Malignancies, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM Rami.komrokji@moffitt.org FU Edward P. Evans Foundation FX M.A.S., G.G.M., G.J.R., D.P.S., A.E.D., C.Z., S.L., J.P.M., and R.S.K. all are grateful to receive support from the Edward P. Evans Foundation. NR 12 TC 1 Z9 1 U1 1 U2 3 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 FEB PY 2016 VL 41 BP 43 EP 47 DI 10.1016/j.leukres.2015.12.007 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA DC5BZ UT WOS:000369236900009 PM 26777537 ER PT J AU de Waal, L Lewis, TA Rees, MG Tsherniak, A Wu, XY Choi, PS Gechijian, L Hartigan, C Faloon, PW Hickey, MJ Tolliday, N Carr, SA Clemons, PA Munoz, B Wagner, BK Shamji, AF Koehler, AN Schenone, M Burgin, AB Schreiber, SL Greulich, H Meyerson, M AF de Waal, Luc Lewis, Timothy A. Rees, Matthew G. Tsherniak, Aviad Wu, Xiaoyun Choi, Peter S. Gechijian, Lara Hartigan, Christina Faloon, Patrick W. Hickey, Mark J. Tolliday, Nicola Carr, Steven A. Clemons, Paul A. Munoz, Benito Wagner, Bridget K. Shamji, Alykhan F. Koehler, Angela N. Schenone, Monica Burgin, Alex B. Schreiber, Stuart L. Greulich, Heidi Meyerson, Matthew TI Identification of cancer-cytotoxic modulators of PDE3A by predictive chemogenomics SO NATURE CHEMICAL BIOLOGY LA English DT Article ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; HISTONE DEACETYLASE INHIBITOR; MOLECULAR PHARMACOLOGY; SIGNALING COMPLEXES; DRUG-SENSITIVITY; ANTICANCER DRUG; ANAGRELIDE; DISCOVERY; 3A; MECHANISMS AB High cancer death rates indicate the need for new anticancer therapeutic agents. Approaches to discovering new cancer drugs include target-based drug discovery and phenotypic screening. Here, we identified phosphodiesterase 3A modulators as cell-selective cancer cytotoxic compounds through phenotypic compound library screening and target deconvolution by predictive chemogenomics. We found that sensitivity to 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one, or DNMDP, across 766 cancer cell lines correlates with expression of the gene PDE3A, encoding phosphodiesterase 3A. Like DNMDP, a subset of known PDE3A inhibitors kill selected cancer cells, whereas others do not. Furthermore, PDE3A depletion leads to DNMDP resistance. We demonstrated that DNMDP binding to PDE3A promotes an interaction between PDE3A and Schlafen 12 (SLFN12), suggestive of a neomorphic activity. Coexpression of SLFN12 with PDE3A correlates with DNMDP sensitivity, whereas depletion of SLFN12 results in decreased DNMDP sensitivity. Our results implicate PDE3A modulators as candidate cancer therapeutic agents and demonstrate the power of predictive chemogenomics in small-molecule discovery. C1 [de Waal, Luc; Lewis, Timothy A.; Rees, Matthew G.; Tsherniak, Aviad; Wu, Xiaoyun; Choi, Peter S.; Gechijian, Lara; Hartigan, Christina; Faloon, Patrick W.; Hickey, Mark J.; Tolliday, Nicola; Carr, Steven A.; Clemons, Paul A.; Munoz, Benito; Wagner, Bridget K.; Shamji, Alykhan F.; Koehler, Angela N.; Schenone, Monica; Burgin, Alex B.; Schreiber, Stuart L.; Greulich, Heidi; Meyerson, Matthew] Broad Inst Harvard & MIT, Cambridge, MA USA. [de Waal, Luc; Choi, Peter S.; Greulich, Heidi; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Koehler, Angela N.] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Greulich, Heidi] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Greulich, H; Meyerson, M (reprint author), Broad Inst Harvard & MIT, Cambridge, MA USA.; Greulich, H; Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Greulich, H (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA USA.; Meyerson, M (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM heidig@broadinstitute.org; matthew_meyerson@dfci.harvard.edu FU US National Cancer Institute (NCI) [1R35CA197568]; American Cancer Society Research Professorship; Doctors Cancer Foundation; Friends of Dana-Farber Cancer Institute; US National Institutes of Health's Molecular Libraries Program Center Network (MLPCN) [3U54HG005032-05S1]; NCI's Cancer Target Discovery and Development (CTD2) Network [U01CA176152] FX This work was supported in part by the US National Cancer Institute (NCI) Grant (grant number 1R35CA197568, awarded to M.M.), the American Cancer Society Research Professorship (awarded to M.M.), the Doctors Cancer Foundation (awarded to H.G.), the Friends of Dana-Farber Cancer Institute (awarded to H.G.), and the US National Institutes of Health's Molecular Libraries Program Center Network (MLPCN) (grant number 3U54HG005032-05S1, awarded to H.G., M.M. and S.L.S.). The cancer cell-line profiling studies were supported in part by the NCI's Cancer Target Discovery and Development (CTD2) Network (grant number U01CA176152, awarded to S.L.S.). We thank A. Bhatt, H. Gannon, J. Jung, T. Sharifnia and all members of the Meyerson laboratory for their advice and helpful discussions. S.L.S. is an Investigator of the Howard Hughes Medical Institute. NR 52 TC 5 Z9 5 U1 5 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD FEB PY 2016 VL 12 IS 2 BP 102 EP + DI 10.1038/NCHEMBIO.1984 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DC6GG UT WOS:000369317300012 PM 26656089 ER PT J AU Rees, MG Seashore-Ludlow, B Cheah, JH Adams, DJ Price, EV Gill, S Javaid, S Coletti, ME Jones, VL Bodycombe, NE Soule, CK Alexander, B Li, A Montgomery, P Kotz, JD Hon, CSY Munoz, B Liefeld, T Dancik, V Haber, DA Clish, CB Bittker, JA Palmer, M Wagner, BK Clemons, PA Shamji, AF Schreiber, SL AF Rees, Matthew G. Seashore-Ludlow, Brinton Cheah, Jaime H. Adams, Drew J. Price, Edmund V. Gill, Shubhroz Javaid, Sarah Coletti, Matthew E. Jones, Victor L. Bodycombe, Nicole E. Soule, Christian K. Alexander, Benjamin Li, Ava Montgomery, Philip Kotz, Joanne D. Hon, C. Suk-Yee Munoz, Benito Liefeld, Ted Dancik, Vlado Haber, Daniel A. Clish, Clary B. Bittker, Joshua A. Palmer, Michelle Wagner, Bridget K. Clemons, Paul A. Shamji, Alykhan F. Schreiber, Stuart L. TI Correlating chemical sensitivity and basal gene expression reveals mechanism of action SO NATURE CHEMICAL BIOLOGY LA English DT Article ID ANTICANCER DRUG-SENSITIVITY; SMALL MOLECULES; CANCER-CELLS; IDENTIFICATION; INHIBITORS; DISCOVERY; TARGET; METABOLISM; PROFILES; RESISTANCE AB Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown. To test this idea, we correlated the sensitivity patterns of 481 compounds with similar to 19,000 basal transcript levels across 823 different human cancer cell lines and identified selective outlier transcripts. This process yielded many novel mechanistic insights, including the identification of activation mechanisms, cellular transporters and direct protein targets. We found that ML239, originally identified in a phenotypic screen for selective cytotoxicity in breast cancer stem-like cells, most likely acts through activation of fatty acid desaturase 2 (FADS2). These data and analytical tools are available to the research community through the Cancer Therapeutics Response Portal. C1 [Rees, Matthew G.; Seashore-Ludlow, Brinton; Cheah, Jaime H.; Adams, Drew J.; Price, Edmund V.; Gill, Shubhroz; Coletti, Matthew E.; Jones, Victor L.; Bodycombe, Nicole E.; Soule, Christian K.; Alexander, Benjamin; Li, Ava; Montgomery, Philip; Kotz, Joanne D.; Hon, C. Suk-Yee; Munoz, Benito; Liefeld, Ted; Dancik, Vlado; Clish, Clary B.; Bittker, Joshua A.; Palmer, Michelle; Wagner, Bridget K.; Clemons, Paul A.; Shamji, Alykhan F.; Schreiber, Stuart L.] Broad Inst, Cambridge, MA USA. [Javaid, Sarah; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Seashore-Ludlow, Brinton] Karolinska Inst, Chem Biol Consortium Sweden, Div Translat Med & Chem Biol, Sci Life Lab Stockholm,Dept Med Biochem & Biophys, Solna, Sweden. [Cheah, Jaime H.; Soule, Christian K.] MIT, Koch Inst Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Adams, Drew J.] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, Cleveland, OH 44106 USA. [Price, Edmund V.] Novartis Inst Biomed Res, Emeryville, CA USA. [Bodycombe, Nicole E.] Pfizer, Cambridge, MA USA. [Liefeld, Ted] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Palmer, Michelle] ImmunoGen, Waltham, MA USA. RP Clemons, PA; Shamji, AF; Schreiber, SL (reprint author), Broad Inst, Cambridge, MA USA. OI Seashore-Ludlow, Brinton/0000-0001-8658-5967 FU US National Cancer Institute's Cancer Target Discovery and Development (CTD2) Network [U01CA176152] FX This work was supported by the US National Cancer Institute's Cancer Target Discovery and Development (CTD2) Network (grant number U01CA176152, awarded to S.L.S.). We acknowledge the following colleagues and centers for contributing compounds and for valuable critique: Boston University, J. Bradner, P. Brown, C. Chen, J. Clardy, CNIO (Spanish National Cancer Research Center), E.J. Corey, the Drug Synthesis and Chemistry Branch (Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute), Eutropics, J. Gutterman, E. Holson, Karyopharm, M. Meyerson, A. Myers, J. Porco, J. Qi, Sanford-Burnham, M. Serrano-Wu, M. Shair, B. Stockwell, L. Walensky, X. Wang and D. Zaharevitz. We thank A. Deik for conducting lipid profiling measurements; S. Chattopadhay, J. Law, G. Schaefer, M. Stewart, V. Viswanathan and other members of the Schreiber laboratory for advice and helpful discussions; S. Wang for helping curate the Informer Set; K. Emmith, J. Aseidu and the CSofT informatics group for development and support of cell-line and data-tracking software; A. Vrcic and the Broad Compound Management team for handling the Informer Set; J. Boehm, A. Tsherniak, A. Aguirre and the Broad Cancer Program for training and advice; the Broad Biological Samples Platform for providing CCLs; and L. Garraway and the Broad-Novartis Cancer Cell Line Encyclopedia (CCLE) team. S.L.S. is an Investigator of the Howard Hughes Medical Institute. NR 49 TC 20 Z9 20 U1 11 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD FEB PY 2016 VL 12 IS 2 BP 109 EP + DI 10.1038/NCHEMBIO.1986 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DC6GG UT WOS:000369317300014 PM 26656090 ER PT J AU Zhang, XY Choi, PS Francis, JM Imielinski, M Watanabe, H Cherniack, AD Meyers, M AF Zhang, Xiaoyang Choi, Peter S. Francis, Joshua M. Imielinski, Marcin Watanabe, Hideo Cherniack, Andrew D. Meyers, Matthew TI Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers SO NATURE GENETICS LA English DT Article ID COPY-NUMBER ALTERATION; B-CELL LINE; LUNG ADENOCARCINOMA; GENE-EXPRESSION; TRANSCRIPTION FACTORS; HUMAN GENOME; C-MYC; SIGNATURES; LEUKEMIA; TRANSFORMATION AB Whole-genome analysis approaches are identifying recurrent cancer-associated somatic alterations in noncoding DNA regions. We combined somatic copy number analysis of 12 tumor types with tissue-specific epigenetic profiling to identify significant regions of focal amplification harboring super-enhancers. Copy number gains of noncoding regions harboring super-enhancers near KLF5, USP12, PARD6B and MYC are associated with overexpression of these cancer-related genes. We show that two distinct focal amplifications of super-enhancers 3' to MYC in lung adenocarcinoma (MYC-LASE) and endometrial carcinoma (MYC-ECSE) are physically associated with the MYC promoter and correlate with MYC overexpression. CRISPR/Cas9-mediated repression or deletion of a constituent enhancer within the MYC-LASE region led to significant reductions in the expression of MYC and its target genes and to the impairment of anchorage independent and clonogenic growth, consistent with an oncogenic function. Our results suggest that genomic amplification of super-enhancers represents a common mechanism to activate cancer driver genes in multiple cancer types. C1 [Zhang, Xiaoyang; Choi, Peter S.; Francis, Joshua M.; Imielinski, Marcin; Meyers, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhang, Xiaoyang; Choi, Peter S.; Francis, Joshua M.; Imielinski, Marcin; Cherniack, Andrew D.; Meyers, Matthew] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Imielinski, Marcin] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Watanabe, Hideo] Icahn Sch Med Mt Sinai, Dept Med, Div Pulm Crit Care & Sleep Med, New York, NY 10029 USA. [Watanabe, Hideo] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Meyers, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Meyers, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. RP Meyers, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Meyers, M (reprint author), Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA.; Meyers, M (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.; Meyers, M (reprint author), Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu FU US Department of Defense [W81XWH-12-1-0269]; National Cancer Institute [1R35CA197568, 1F32CA180662]; American Cancer Society; Lung Cancer Research Foundation; American Association for Cancer Research-John and Elizabeth Leonard Family Foundation; International Association for the Study of Lung Cancer FX We thank G. Ha and other members of the Meyerson laboratory for discussions. We acknowledge support from US Department of Defense grant W81XWH-12-1-0269 (KM.), National Cancer Institute grant 1R35CA197568 (KM.) and the American Cancer Society Research Professorship (KM.). X.Z. is supported by the Lung Cancer Research Foundation and the American Association for Cancer Research-John and Elizabeth Leonard Family Foundation Basic Cancer Research Fellowship. P.S.C. is supported by a fellowship from the International Association for the Study of Lung Cancer and National Cancer Institute grant 1F32CA180662. NR 49 TC 28 Z9 29 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD FEB PY 2016 VL 48 IS 2 BP 176 EP 182 DI 10.1038/ng.3470 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA DC2JV UT WOS:000369043900015 PM 26656844 ER PT J AU Bailey, JNC Loomis, SJ Kang, JH Allingham, RR Gharahkhani, P Khor, CC Burdon, KP Aschard, H Chasman, DI Igo, RP Hysi, PG Glastonbury, CA Ashley-Koch, A Brilliant, M Brown, AA Budenz, DL Buil, A Cheng, CY Choi, H Christen, WG Curhan, G De Vivo, I Fingert, JH Foster, PJ Fuchs, C Gaasterland, D Gaasterland, T Hewitt, AW Hu, F Hunter, DJ Khawaja, AP Lee, RK Li, Z Lichter, PR Mackey, DA McGuffin, P Mitchell, P Moroi, SE Perera, SA Pepper, KW Qi, QB Realini, T Richards, JE Ridker, PM Rimm, E Ritch, R Ritchie, M Schuman, JS Scott, WK Singh, K Sit, AJ Song, YE Tamimi, RM Topouzis, F Viswanathan, AC Verma, SS Vollrath, D Wang, JJ Weisschuh, N Wissinger, B Wollstein, G Wong, TY Yaspan, BL Zack, DJ Zhang, K Weinreb, RN Pericak-Vance, MA Small, K Hammond, CJ Aung, T Liu, YT Vithana, EN MacGregor, S Craig, JE Kraftl, P Howell, G Hauser, MA Pasguale, LR Haines, JL Wiggs, JL AF Bailey, Jessica N. Cooke Loomis, Stephanie J. Kang, Jae H. Allingham, R. Rand Gharahkhani, Puya Khor, Chiea Chuen Burdon, Kathryn P. Aschard, Hugues Chasman, Daniel I. Igo, Robert P., Jr. Hysi, Pirro G. Glastonbury, Craig A. Ashley-Koch, Allison Brilliant, Murray Brown, Andrew A. Budenz, Donald L. Buil, Alfonso Cheng, Ching-Yu Choi, Hyon Christen, William G. Curhan, Gary De Vivo, Immaculata Fingert, John H. Foster, Paul J. Fuchs, Charles Gaasterland, Douglas Gaasterland, Terry Hewitt, Alex W. Hu, Frank Hunter, David J. Khawaja, Anthony P. Lee, Richard K. Li, Zheng Lichter, Paul R. Mackey, David A. McGuffin, Peter Mitchell, Paul Moroi, Sayoko E. Perera, Shamira A. Pepper, Keating W. Qi, Qibin Realini, Tony Richards, Julia E. Ridker, Paul M. Rimm, Eric Ritch, Robert Ritchie, Marylyn Schuman, Joel S. Scott, William K. Singh, Kuldev Sit, Arthur J. Song, Yeunjoo E. Tamimi, Rulla M. Topouzis, Fotis Viswanathan, Ananth C. Verma, Shefali Setia Vollrath, Douglas Wang, Jie Jin Weisschuh, Nicole Wissinger, Bernd Wollstein, Gadi Wong, Tien Y. Yaspan, Brian L. Zack, Donald J. Zhang, Kang Weinreb, Robert N. Pericak-Vance, Margaret A. Small, Kerrin Hammond, Christopher J. Aung, Tin Liu, Yutao Vithana, Eranga N. MacGregor, Stuart Craig, Jamie E. Kraftl, Peter Howell, Gareth Hauser, Michael A. Pasguale, Louis R. Haines, Jonathan L. Wiggs, Janey L. CA EPIC Norfolk Eye Study ANZRAG Consortium TI Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma SO NATURE GENETICS LA English DT Article ID COMMON VARIANTS; INTRAOCULAR-PRESSURE; GENOTYPE IMPUTATION; METAANALYSIS; STRESS; NUMBER; DYSFUNCTION; PREVALENCE; ANNOTATION; MUTATIONS AB Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 x 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 x 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 x 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies. C1 [Bailey, Jessica N. Cooke; Igo, Robert P., Jr.; Song, Yeunjoo E.; Haines, Jonathan L.] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Inst Computat Biol, Cleveland, OH 44106 USA. [Loomis, Stephanie J.; Pasguale, Louis R.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Kang, Jae H.; Curhan, Gary; De Vivo, Immaculata; Fuchs, Charles; Rimm, Eric; Tamimi, Rulla M.; Pasguale, Louis R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Allingham, R. Rand; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [Gharahkhani, Puya; MacGregor, Stuart] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Khor, Chiea Chuen; Li, Zheng] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Khor, Chiea Chuen; Cheng, Ching-Yu; Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore. [Burdon, Kathryn P.; Mackey, David A.] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia. [Burdon, Kathryn P.; Craig, Jamie E.] Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA 5001, Australia. [Aschard, Hugues; Hu, Frank; Hunter, David J.; Rimm, Eric; Kraftl, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chasman, Daniel I.; Christen, William G.; Ridker, Paul M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Hysi, Pirro G.; Glastonbury, Craig A.; Small, Kerrin; Hammond, Christopher J.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. [Ashley-Koch, Allison; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Brilliant, Murray] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Brown, Andrew A.; Buil, Alfonso] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Budenz, Donald L.] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA. [Cheng, Ching-Yu; Perera, Shamira A.; Wong, Tien Y.; Aung, Tin; Vithana, Eranga N.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore. [Cheng, Ching-Yu; Aung, Tin; Vithana, Eranga N.] Duke Nat Univ Singapore Grad Med Sch, Eye Acad Clin Program, Singapore, Singapore. [Choi, Hyon] Boston Univ, Sch Med, Sect Rheumatol & Clin Epidemiol Unit, Boston, MA 02118 USA. [Curhan, Gary] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [Fingert, John H.] Univ Iowa, Coll Med, Dept Ophthalmol, Iowa City, IA 52242 USA. [Fingert, John H.] Univ Iowa, Coll Med, Dept Anat & Cell Biol, Iowa City, IA USA. [Foster, Paul J.; Viswanathan, Ananth C.] Moorfields Eye Hosp, Biomed Res Ctr, Nat Inst Hlth Res, London, England. [Foster, Paul J.] UCL, Dept Ophthalmol, London, England. [Fuchs, Charles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Gaasterland, Douglas] Eye Doctors Washington, Chevy Chase, MD USA. [Gaasterland, Terry] Univ Calif San Diego, Scripps Genome Ctr, San Diego, CA 92103 USA. [Hewitt, Alex W.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia. [Hewitt, Alex W.] Royal Victorian Eye & Ear Hosp, Dept Ophthalmol, Melbourne, Vic 3002, Australia. [Hu, Frank; Rimm, Eric] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hunter, David J.; Kraftl, Peter] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 665 Huntington Ave, Boston, MA 02115 USA. [Khawaja, Anthony P.] Univ Cambridge, Sch Clin Med, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. [Lee, Richard K.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Lichter, Paul R.; Moroi, Sayoko E.; Richards, Julia E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Mackey, David A.] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia. [McGuffin, Peter] Kings Coll London, Inst Psychiat, Med Res Council Social Genet & Dev Psychiat Res C, London, England. [Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Westmead Millennium Inst, Ctr Vis Res, Westmead, NSW 2145, Australia. [Perera, Shamira A.] Duke Natl Univ Singapore Grad Med Sch, Singapore, Singapore. [Pepper, Keating W.; Howell, Gareth] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. [Qi, Qibin] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Realini, Tony] West Virginia Univ Eye Inst, Dept Ophthalmol, Morgantown, WV USA. [Richards, Julia E.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Ritch, Robert] New York Eye & Ear Infirm Mt Sinai, Dept Ophthalmol, Einhorn Clin Res Ctr, New York, NY USA. [Ritchie, Marylyn; Verma, Shefali Setia] Penn State Univ, Ctr Syst Genom, University Pk, PA 16802 USA. [Schuman, Joel S.; Wollstein, Gadi] Univ Pittsburgh, Dept Ophthalmol, Pittsburgh, PA 15260 USA. [Scott, William K.; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Inst Human Genom, Miami, FL 33136 USA. [Singh, Kuldev] Stanford Univ, Sch Med, Dept Ophthalmol, Palo Alto, CA 94304 USA. [Sit, Arthur J.] Mayo Clin, Dept Ophthalmol, Rochester, MN USA. [Topouzis, Fotis] Aristotle Univ Thessaloniki, AHEPA Hosp, Sch Med, Dept Ophthalmol, GR-54006 Thessaloniki, Greece. [Vollrath, Douglas] Stanford Univ, Sch Med, Dept Genet, Palo Alto, CA 94304 USA. [Weisschuh, Nicole; Wissinger, Bernd] Univ Tubingen, Ctr Ophthalmol, Inst Ophthalmic Res, Tubingen, Germany. [Yaspan, Brian L.] Genentech Inc, 460 Point San Bruno Blvd, San Francisco, CA 94080 USA. [Zack, Donald J.] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD USA. [Zhang, Kang; Weinreb, Robert N.] Univ Calif San Diego, Shiley Eye Inst, Hamilton Glaucoma Ctr, San Diego, CA 92103 USA. [Liu, Yutao] Georgia Regents Univ, Dept Cell Biol & Anat, Augusta, GA USA. [Liu, Yutao] Georgia Regents Univ, James & Jean Culver Vis Discovery Inst, Augusta, GA USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. EM janey_wiggs@meei.harvard.edu RI Hewitt, Alex/D-1936-2013; Macgregor, Stuart/C-6442-2009; Mitchell, Paul/P-1498-2014; Wang, Jie Jin/P-1499-2014; Burdon, Kathryn/A-5026-2009; OI Ashley-Koch, Allison/0000-0001-5409-9155; Hammond, Christopher/0000-0002-3227-2620; Mackey, David/0000-0001-7914-4709; Gharahkhani, Puya/0000-0002-4203-5952; Hewitt, Alex/0000-0002-5123-5999; Brown, Andrew/0000-0002-8087-3033; Macgregor, Stuart/0000-0001-6731-8142; Perera, Shamira/0000-0002-1404-5096; Small, Kerrin/0000-0003-4566-0005; Wang, Jie Jin/0000-0001-9491-4898; Burdon, Kathryn/0000-0001-8217-1249; Li , Zheng/0000-0002-7060-2213; Buil, Alfonso/0000-0002-3097-1014; Cooke Bailey, Jessica/0000-0002-4001-8702 FU US National Institutes of Health/National Eye Institute (NIH/NEI) [R01EY022305]; UK Medical Research Council [G1000143]; Cancer Research UK [C864/A14136]; NHMRC; Centre for Clinical Research Excellence in Translational Clinical Research in Eye Diseases; Wellcome Trust, UK; National Institute for Health Research (NIHR); Fight for Sight Early Career Investigator Award; Biomedical Research Council (BMRC) grant in Singapore [BMRC 10/1/35/19/675]; Singapore National Research Foundation [NMRC/TCR/008-SERI/2013]; Royal Australian and New Zealand College of Ophthalmology (RANZCO) Eye Foundation; National Health and Medical Research Council (NHMRC) of Australia [535074, 1031362, 1023911, 1021105] FX NEIGHBORHOOD data collection and analysis are supported by US National Institutes of Health/National Eye Institute (NIH/NEI) grant R01EY022305 (J.L.W.). Support for recruitment in ANZRAG (Australian and New Zealand Registry of Advanced Glaucoma) was provided by the Royal Australian and New Zealand College of Ophthalmology (RANZCO) Eye Foundation and by the National Health and Medical Research Council (NHMRC) of Australia (535074, 1031362, 1023911 and 1021105). EPIC-Norfolk infrastructure and core functions are supported by grants from the UK Medical Research Council (G1000143) and Cancer Research UK (C864/A14136). BMES (Blue Mountains Eye Study) was supported by the NHMRC, the Centre for Clinical Research Excellence in Translational Clinical Research in Eye Diseases, NHMRC Senior Research Fellowships and the Wellcome Trust, UK. Collection and genotyping for the South London Case-Control cohort (UK) were supported by a National Institute for Health Research (NIHR) Senior Research Fellowship (C.J.H.), and analysis was supported by a Fight for Sight Early Career Investigator Award (P.J.H.). The Singapore study (E.N.V., T.A. and C.C.K.) was supported by a Biomedical Research Council (BMRC) grant in Singapore, reference BMRC 10/1/35/19/675. This research was also partly supported by a grant (NMRC/TCR/008-SERI/2013) from the Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council. Additional acknowledgment and funding details are in the Supplementary Note. NR 47 TC 23 Z9 23 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD FEB PY 2016 VL 48 IS 2 BP 189 EP 194 DI 10.1038/ng.3482 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA DC2JV UT WOS:000369043900017 PM 26752265 ER PT J AU Kim, KH Roberts, CWM AF Kim, Kimberly H. Roberts, Charles W. M. TI Targeting EZH2 in cancer SO NATURE MEDICINE LA English DT Review ID POLYCOMB-REPRESSIVE COMPLEX; HISTONE METHYLTRANSFERASE EZH2; GROUP PROTEIN EZH2; EMBRYONIC STEM-CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHROMATIN REMODELING GENES; NERVE SHEATH TUMORS; SOMATIC MUTATIONS; PROSTATE-CANCER; BREAST-CANCER AB Recent genomic studies have resulted in an emerging understanding of the role of chromatin regulators in the development of cancer. EZH2, a histone methyl transferase subunit of a Polycomb repressor complex, is recurrently mutated in several forms of cancer and is highly expressed in numerous others. Notably, both gain-of-function and loss-of-function mutations occur in cancers but are associated with distinct cancer types. Here we review the spectrum of EZH2-associated mutations, discuss the mechanisms underlying EZH2 function, and synthesize a unifying perspective that the promotion of cancer arises from disruption of the role of EZH2 as a master regulator of transcription. We further discuss EZH2 inhibitors that are now showing early signs of promise in clinical trials and also additional strategies to combat roles of EZH2 in cancer. C1 [Kim, Kimberly H.; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kim, Kimberly H.; Roberts, Charles W. M.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Kim, Kimberly H.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kim, Kimberly H.; Roberts, Charles W. M.] Broad Inst Harvard, Boston, MA USA. [Kim, Kimberly H.; Roberts, Charles W. M.] MIT, Boston, MA USA. [Roberts, Charles W. M.] St Jude Childrens Res Hosp, Ctr Comprehens Canc, 332 N Lauderdale St, Memphis, TN 38105 USA. [Roberts, Charles W. M.] St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. RP Roberts, CWM (reprint author), St Jude Childrens Res Hosp, Ctr Comprehens Canc, 332 N Lauderdale St, Memphis, TN 38105 USA.; Roberts, CWM (reprint author), St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM Charles.Roberts@stjude.org FU National Cancer Center; US National Cancer Institute [R01CA172152, R01CA113794]; Garrett B. Smith Foundation; Cure AT/RT Now foundation; Avalanna Fund; Miles for Mary FX K.H.K. was supported by an award from the National Cancer Center. C.W.M.R. was supported by US National Cancer Institute grants R01CA172152 and R01CA113794. The Garrett B. Smith Foundation, the Cure AT/RT Now foundation, The Avalanna Fund and Miles for Mary provided additional support. NR 122 TC 55 Z9 57 U1 21 U2 46 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD FEB PY 2016 VL 22 IS 2 BP 128 EP 134 DI 10.1038/nm.4036 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DC8JX UT WOS:000369466800005 PM 26845405 ER PT J AU Cloonan, SM Glass, K Laucho-Contreras, ME Bhashyam, AR Cervo, M Pabon, MA Konrad, C Polverino, F Siempos, II Perez, E Mizumura, K Ghosh, MC Parameswaran, H Williams, NC Rooney, KT Chen, ZH Goldklang, MP Yuan, GC Moore, SC Demeo, DL Rouault, TA D'Armiento, JM Schon, EA Manfredi, G Quackenbush, J Mahmood, A Silverman, EK Owen, CA Choi, AMK AF Cloonan, Suzanne M. Glass, Kimberly Laucho-Contreras, Maria E. Bhashyam, Abhiram R. Cervo, Morgan Pabon, Maria A. Konrad, Csaba Polverino, Francesca Siempos, Ilias I. Perez, Elizabeth Mizumura, Kenji Ghosh, Manik C. Parameswaran, Harikrishnan Williams, Niamh C. Rooney, Kristen T. Chen, Zhi-Hua Goldklang, Monica P. Yuan, Guo-Cheng Moore, Stephen C. Demeo, Dawn L. Rouault, Tracey A. D'Armiento, Jeanine M. Schon, Eric A. Manfredi, Giovanni Quackenbush, John Mahmood, Ashfaq Silverman, Edwin K. Owen, Caroline A. Choi, Augustine M. K. TI Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice SO NATURE MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; CYTOCHROME-C-OXIDASE; GENOME-WIDE ASSOCIATION; GENE-EXPRESSION; REGULATORY PROTEIN-2; TARGETED DELETION; LUNG-CANCER; COPD; DEFICIENCY; ANEMIA AB Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene and have shown that IRP2 protein is increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RNA immunoprecipitation followed by sequencing (RIP-seq), RNA sequencing (RNA-seq), and gene expression and functional enrichment clustering analysis, we identified Irp2 as a regulator of mitochondrial function in the lungs of mice. Irp2 increased mitochondrial iron loading and levels of cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice, which had higher mitochondria! iron loading, showed impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas mice deficient in the synthesis of cytochrome c oxidase, which have reduced COX, were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondria! iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-induced impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. C1 [Cloonan, Suzanne M.; Pabon, Maria A.; Siempos, Ilias I.; Perez, Elizabeth; Mizumura, Kenji; Williams, Niamh C.; Rooney, Kristen T.; Choi, Augustine M. K.] New York Presbyterian Hosp, Weill Cornell Med Coll, Joan & Sanford I Weill Dept Med, New York, NY USA. [Cloonan, Suzanne M.; Laucho-Contreras, Maria E.; Bhashyam, Abhiram R.; Polverino, Francesca; Mizumura, Kenji; Chen, Zhi-Hua; Demeo, Dawn L.; Silverman, Edwin K.; Owen, Caroline A.; Choi, Augustine M. K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Glass, Kimberly; Yuan, Guo-Cheng; Quackenbush, John] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Glass, Kimberly; Yuan, Guo-Cheng; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Glass, Kimberly; Demeo, Dawn L.; Quackenbush, John; Silverman, Edwin K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Cervo, Morgan; Moore, Stephen C.; Mahmood, Ashfaq] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Konrad, Csaba; Manfredi, Giovanni] Weill Cornell Med Coll, Brain & Mind Res Inst, New York, NY USA. [Polverino, Francesca; Owen, Caroline A.] Lovelace Resp Res Inst, Albuquerque, NM USA. [Polverino, Francesca] Univ Parma, Dept Pulm, I-43100 Parma, Italy. [Siempos, Ilias I.] Univ Athens, Sch Med, Evangelismos Hosp, Dept Crit Care Med & Pulm Serv 1, Athens, Greece. [Ghosh, Manik C.; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Parameswaran, Harikrishnan] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Chen, Zhi-Hua] Zhejiang Univ, Sch Med, Dept Resp & Crit Care Med, Hosp 2, Hangzhou, Zhejiang, Peoples R China. [Goldklang, Monica P.; D'Armiento, Jeanine M.] Columbia Univ, Dept Anesthesiol, New York, NY USA. [Goldklang, Monica P.; D'Armiento, Jeanine M.] Columbia Univ, Dept Med, New York, NY USA. [D'Armiento, Jeanine M.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY USA. [Schon, Eric A.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. [Schon, Eric A.] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY USA. RP Choi, AMK (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, Joan & Sanford I Weill Dept Med, New York, NY USA.; Choi, AMK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. EM amc2056@med.cornell.edu RI Polverino, Francesca/F-3816-2017; OI Polverino, Francesca/0000-0001-9686-5698; Rooney, Kristen T/0000-0002-7495-1437 FU US National Institutes of Health (NIH) [P01-HL114501, R01-HL055330, R01-HL079904, R01-A1111475-01, R01-HL86814, R21-HL111835, HL122513, R01-HL086936, P01-HD080642]; NIH-National Heart, Lung and Blood Institute [K99-HL125899]; American Lung Association Biomedical Research [RG-348928]; Flight Attendants Medical Research Institute (FAMRI) clinical innovator award; clinical innovator FAMRI [CIA 123046]; FAMRI Young Clinical Scientist a [YFEL141004, YFEL103236]; US Department of Defense [W911F-15-1-0169]; NIH [P01-HL114501, P01-HL105339, R01-HL111759, R21-ES025379-01, R01-GM088999]; Brigham and Women's Hospital-Lovelace Respiratory Research institute Research Consortium; intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH; Muscular Dystrophy Association; J. Willard and Alice S. Marriott Foundation FX The authors thank J.S. Moon, H.C. Lam, K. Taylor and B. Ding for technical assistance. The authors also acknowledge S. Chan (Harvard Medical School) for the cyto-GRX2 and mito-GRX2 plasmids, Y. Hua (Columbia University) for the breeding of the Sco2ki/ki and Sco2ki/ko mice and J. Connelly (ApoPharma Inc.) for providing Ferriprox. The authors also thank R. Rubio for assistance with RNA-seq, Y. Shao for assistance with the microarray study and M. Ericsson for assistance with transmission electron microscopy. The authors also acknowledge discussion and input from S.W. Ryter, C.A. MacRae and P.Y. Sips. This work was supported by US National Institutes of Health (NIH) grants P01-HL114501 (A.M.K.C.), R01-HL055330 (A.M.K.C.), R01-HL079904 (A.M.K.C.), R01-A1111475-01 (C.A.O.), R01-HL86814 (C.A.O.), R21-HL111835 (C.A.O.), HL122513 (H.P.), R01-HL086936 (to J.M.D'A.) and P01-HD080642 (Project 2 to E.A.S.), NIH-National Heart, Lung and Blood Institute grant K99-HL125899 (S.M.C.), American Lung Association Biomedical Research grant RG-348928 (S.M.C.), a Flight Attendants Medical Research Institute (FAMRI) clinical innovator award (A.M.K.C.), clinical innovator FAMRI grant CIA#123046 (C.A.O.), FAMRI Young Clinical Scientist awards YFEL141004 (F.P.) and YFEL103236 (M.P.G.), and US Department of Defense grant W911F-15-1-0169 (E.A.S.). S.M.C., A.M.K.C., J.Q. and E.K.S. were also supported by NIH grant P01-HL105339 (to E.K.S.). K.G. was supported by NIH grant R01-HL111759 (to J.Q., G.C.Y. and E.K.S.). C.A.O. was also supported by NIH grants R21-ES025379-01 (to A. Fedulov), P01-HL105339 (to E.K.S.) and P01-HL114501 (to A.M.K.C.) and by Brigham and Women's Hospital-Lovelace Respiratory Research institute Research Consortium grants. G.M. and C.K. were supported by NIH grant R01-GM088999 (to G.M.). M.C.G. and T.A.R. acknowledge support from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. Additional support was provided by the Muscular Dystrophy Association (E.A.S.) and the J. Willard and Alice S. Marriott Foundation (E.A.S.). NR 60 TC 9 Z9 9 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD FEB PY 2016 VL 22 IS 2 BP 163 EP 174 DI 10.1038/nm.4021 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DC8JX UT WOS:000369466800010 PM 26752519 ER PT J AU Dotiwala, F Mulik, S Polidoro, RB Ansara, JA Burleigh, BA Walchs, M Gazzinelli, RT Lieberman, J AF Dotiwala, Farokh Mulik, Sachin Polidoro, Rafael B. Ansara, James A. Burleigh, Barbara A. Walchs, Michael Gazzinelli, Ricardo T. Lieberman, Judy TI Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites SO NATURE MEDICINE LA English DT Article ID PROGRAMMED CELL-DEATH; CD8(+) T-CELLS; TRYPANOSOMA-CRUZI; IMMUNE-RESPONSE; MICE; GLUTATHIONE; PEROXIDASE; LESSONS; DISEASE AB Protozoan infections are a serious global health problem(1,2). Natural killer (NK) cells and cytolytic T lymphocytes (CTLs) eliminate pathogen-infected cells by releasing cytolytic granule contents granzyme (Gzm) proteases and the pore-forming perforin (PFN)-into the infected cell(3). However, these cytotoxic molecules do not kill intracellular parasites. CD8(+) CTLs protect against parasite infections in mice primarily by secreting interferon (IFN)-gamma(4-10). However, human, but not rodent, cytotoxic granules contain the antimicrobial peptide granulysin (GNLY), which selectively destroys cholesterol poor microbial membranes(11-14), and GNLY, PFN and Gzms rapidly kill intracellular bacteria(15). Here we show that GNLY delivers Gzms into three protozoan parasites (Trypanosoma cruzi, Toxoplasma gondii and Leishmania major), in which the Gzms generate superoxide and inactivate oxidative defense enzymes to kill the parasite. PFN delivers GNLY and Gzms into infected cells, and GNLY then delivers Gzms to the intracellular parasites. Killer cell-mediated parasite death, which we term 'microbe-programmed cell death' or 'microptosis', is caspase independent but resembles mammalian apoptosis, causing mitochondria! swelling, transmembrane potential dissipation, membrane blebbing, phosphatidylserine exposure, DNA damage and chromatin condensation. GNLY-transgenic mice are protected against infection by T. cruzi and T. gondii, and survive infections that are lethal to wild-type mice. Thus, GNLY-, PFN- and Gzm-mediated elimination of intracellular protozoan parasites is an unappreciated immune defense mechanism. C1 [Dotiwala, Farokh; Mulik, Sachin; Polidoro, Rafael B.; Ansara, James A.; Lieberman, Judy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Dotiwala, Farokh; Mulik, Sachin; Polidoro, Rafael B.; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Polidoro, Rafael B.; Gazzinelli, Ricardo T.] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil. [Burleigh, Barbara A.; Gazzinelli, Ricardo T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. [Walchs, Michael] Univ Fribourg, Dept Med, CH-1700 Fribourg, Switzerland. [Gazzinelli, Ricardo T.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. RP Dotiwala, F; Lieberman, J (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA.; Dotiwala, F; Lieberman, J (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.; Gazzinelli, RT (reprint author), Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil.; Gazzinelli, RT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA.; Gazzinelli, RT (reprint author), Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. EM farokh.dotiwala@childrens.harvard.edu; ricardo.gazzinelli@umassmed.edu; jbdy.lieberman@childrens.harvard.edu RI Polidoro, Rafael/A-6385-2016 OI Polidoro, Rafael/0000-0003-2982-0072 FU US National Institutes of Health [T32HL066987]; Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior (CAPES); David Rockefeller Center for Latin American Studies at Harvard University; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Brazilian National Institute of Science and Technology for Vaccines [CNPq/Fapemig/MS 573547/2008-4] FX This work was supported by the US National Institutes of Health grant T32HL066987 (F.D.), a Scholar Fellowship from Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior (CAPES) and the David Rockefeller Center for Latin American Studies at Harvard University (R.T.G.), a Science Without Borders Scholar Fellowship from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (R.B.P.) and the Brazilian National Institute of Science and Technology for Vaccines grant CNPq/Fapemig/MS 573547/2008-4 (R.T.G.). We thank S. Wilkinson (Queen Mary University, London) and J. Kelly (London School of Hygiene and Tropical Medicine) for T. cruzi overexpression plasmids, K. Okuda (University of Massachusetts Medical School) for L. major, K. Engelberg and M.J. Gubbels (Boston College) for T gondii, and M. Ericsson and R. Bronson (Harvard Medical School) for technical support. NR 20 TC 7 Z9 7 U1 4 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD FEB PY 2016 VL 22 IS 2 BP 210 EP 216 DI 10.1038/nm.4023 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DC8JX UT WOS:000369466800015 PM 26752517 ER PT J AU Morrell, NW Bloch, DB ten Dijke, P Goumans, MJTH Hata, A Smith, J Yu, PB Bloch, KD AF Morrell, Nicholas W. Bloch, Donald B. ten Dijke, Peter Goumans, Marie-Jose T. H. Hata, Akiko Smith, Jim Yu, Paul B. Bloch, Kenneth D. TI Targeting BMP signalling in cardiovascular disease and anaemia SO NATURE REVIEWS CARDIOLOGY LA English DT Review ID BONE MORPHOGENETIC PROTEIN; HEREDITARY HEMORRHAGIC TELANGIECTASIA; PULMONARY ARTERIAL-HYPERTENSION; SMOOTH-MUSCLE-CELLS; PLURIPOTENT STEM-CELLS; BLOOD-VESSEL FORMATION; TRANSFORMING GROWTH FACTOR-BETA(1); PATHOLOGICAL CARDIAC-HYPERTROPHY; SUPPRESSES TUMOR-GROWTH; RECEPTOR-LIKE KINASE-1 AB Bone morphogenetic proteins (BMPs) and their receptors, known to be essential regulators of embryonic patterning and organogenesis, are also critical for the regulation of cardiovascular structure and function. In addition to their contributions to syndromic disorders including heart and vascular development, BMP signalling is increasingly recognized for its influence on endocrine-like functions in postnatal cardiovascular and metabolic homeostasis. In this Review, we discuss several critical and novel aspects of BMP signalling in cardiovascular health and disease, which highlight the cell-specific and context-specific nature of BMP signalling. Based on advancing knowledge of the physiological roles and regulation of BMP signalling, we indicate opportunities for therapeutic intervention in a range of cardiovascular conditions including atherosclerosis and pulmonary arterial hypertension, as well as for anaemia of inflammation. Depending on the context and the repertoire of ligands and receptors involved in specific disease processes, the selective inhibition or enhancement of signalling via particular BMP ligands (such as in atherosclerosis and pulmonary arterial hypertension, respectively) might be beneficial. The development of selective small molecule antagonists of BMP receptors, and the identification of ligands selective for BMP receptor complexes expressed in the vasculature provide the most immediate opportunities for new therapies. C1 [Morrell, Nicholas W.] Univ Cambridge, Sch Clin Med, Addenbrookes Hosp, Dept Med, Hills Road, Cambridge CB2 0QQ, England. [Bloch, Donald B.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Bloch, Donald B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [ten Dijke, Peter; Goumans, Marie-Jose T. H.] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RA Leiden, Netherlands. [ten Dijke, Peter; Goumans, Marie-Jose T. H.] Leiden Univ, Med Ctr, Canc Genom Ctr Netherlands, NL-2300 RA Leiden, Netherlands. [Hata, Akiko] Univ Calif, Cardiovasc Res Inst, Davis, CA USA. [Smith, Jim] MRC Natl Inst Med Res, London, England. [Yu, Paul B.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bloch, Kenneth D.] Anaesthesia Ctr Crit Care Res, Dept Anaesthesia Crit Care & Pain, Oxford, MS USA. RP Morrell, NW (reprint author), Univ Cambridge, Sch Clin Med, Addenbrookes Hosp, Dept Med, Hills Road, Cambridge CB2 0QQ, England. EM nwm23@cam.ac.uk OI Yu, Paul/0000-0003-2145-4944 FU British Heart Foundation [RG/13/4/30107]; Medical Research Council [G0800784, G1000847, MC_U117597140, MR/K020919/1]; NHLBI NIH HHS [K08 HL079943]; NIAMS NIH HHS [R01 AR057374]; NIDDK NIH HHS [R01 DK082971] NR 214 TC 10 Z9 13 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 EI 1759-5010 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD FEB PY 2016 VL 13 IS 2 BP 106 EP 120 DI 10.1038/nrcardio.2015.156 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DC6JH UT WOS:000369325600011 PM 26461965 ER PT J AU Alhamud, A Taylor, PA van der Kouwe, AJW Meintjes, EM AF Alhamud, A. Taylor, Paul A. van der Kouwe, Andre J. W. Meintjes, Ernesta M. TI Real-time measurement and correction of both B0 changes and subject motion in diffusion tensor imaging using a double volumetric navigated (DvNav) sequence SO NEUROIMAGE LA English DT Article DE Diffusion tensor imaging (DTI); Zero-order shim (frequency); The first-order shim (linear gradients); Navigated diffusion sequence (vNav); Double volumetric navigators (DvNav); B0 correction ID NORMAL BRAIN MATURATION; STATIC MAGNETIC-FIELD; ECHO-PLANAR IMAGES; INDUCED DISTORTION; FRACTIONAL ANISOTROPY; ARTIFACT REDUCTION; SPIN-ECHO; MRI; SPECTROSCOPY; CHILDHOOD AB Diffusion tensor imaging (DTI) requires a set of diffusion weighted measurements in order to acquire enough information to characterize local structure. The MRI scanner automatically performs a shimming process by acquiring a field map before the start of a DTI scan. Changes in B0, which can occur throughout the DTI acquisition due to several factors (including heating of the iron shim coils or subject motion), cause significant signal distortions that result in warped diffusion tensor (DT) parameter estimates. In this work we introduce a novel technique to simultaneously measure, report and correct in real time subject motion and changes in B0 field homogeneity, both in and through the imaging plane. This is achieved using double volumetric navigators (DvNav), i.e. a pair of 3D EPI acquisitions, interleaved with the DTI pulse sequence. Changes in the B0 field are evaluated in terms of zero-order (frequency) and first-order (linear gradients) shim. The ability of the DvNav to accurately estimate the shim parameters was first validated in a water phantom. Two healthy subjects were scanned both in the presence and absence of motion using standard, motion corrected (single navigator, vNav), and DvNav DTI sequences. The difference in performance between the proposed 3D EPI field maps and the standard 3D gradient echo field maps of the MRI scanner was also evaluated in a phantom and two healthy subjects. The DvNav sequence was shown to accurately measure and correct changes in B0 following manual adjustments of the scanner's central frequency and the linear shim gradients. Compared to other methods, the DvNav produced DTI results that showed greater spatial overlap with anatomical references, particularly in scans with subject motion. This is largely due to the ability of the DvNav system to correct shim changes and subject motion between each volume acquisition, thus reducing shear distortion. (C) 2015 Elsevier Inc. All rights reserved. C1 [Alhamud, A.; Taylor, Paul A.; Meintjes, Ernesta M.] Univ Cape Town, Dept Human Biol, MRC UCT Med Imaging Res Unit, ZA-7700 Rondebosch, South Africa. [Taylor, Paul A.] AIMS, Muizenberg, South Africa. [van der Kouwe, Andre J. W.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [van der Kouwe, Andre J. W.] Harvard Univ, Sch Med, Dept Radiol, Brookline, MA USA. RP Alhamud, A (reprint author), Univ Cape Town, Dept Human Biol, MRC UCT Med Imaging Res Unit, ZA-7700 Rondebosch, South Africa. EM alkk1973@gmail.com FU NIAAA NIH HHS [R21 AA017410]; NICHD NIH HHS [R01 HD071664]; NIMH NIH HHS [R21 MH096559] NR 58 TC 2 Z9 2 U1 4 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2016 VL 126 BP 60 EP 71 DI 10.1016/j.neuroimage.2015.11.022 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DC5VX UT WOS:000369289800006 PM 26584865 ER PT J AU Whiteman, AS Young, DE Budson, AE Stern, CE Schon, K AF Whiteman, Andrew S. Young, Daniel E. Budson, Andrew E. Stern, Chantal E. Schon, Karin TI Entorhinal volume, aerobic fitness, and recognition memory in healthy young adults: A voxel-based morphometry study SO NEUROIMAGE LA English DT Article DE Medial temporal lobes; Hippocampus; Recognition memory; Cardiovascular fitness; Neurotrophins ID MILD COGNITIVE IMPAIRMENT; MEDIAL TEMPORAL-LOBE; RAT CEREBRAL-CORTEX; GRAY-MATTER VOLUME; HIPPOCAMPAL VOLUME; DENTATE GYRUS; ENVIRONMENTAL ENRICHMENT; PHYSICAL-ACTIVITY; MESSENGER-RNA; CARDIORESPIRATORY FITNESS AB Converging evidence supports the hypothesis effects of aerobic exercise and environmental enrichment are beneficial for cognition, in particular for hippocampus-supported learning and memory. Recent work in humans suggests that exercise training induces changes in hippocampal volume, but it is not known if aerobic exercise and fitness also impact the entorhinal cortex. In animal models, aerobic exercise increases expression of growth factors, including brain derived neurotrophic factor (BDNF). This exercise-enhanced expression of growth hormones may boost synaptic plasticity, and neuronal survival and differentiation, potentially supporting function and structure in brain areas including but not limited to the hippocampus. Here, using voxel based morphometry and a standard graded treadmill test to determine cardio-respiratory fitness (Bruce protocol; VO2 max), we examined if entorhinal and hippocampal volumes were associated with cardio-respiratory fitness in healthy young adults (N = 33). In addition, we examined if volumes were modulated by recognition memory performance and by serum BDNF, a putative marker of synaptic plasticity. Our results show a positive association between volume in right entorhinal cortex and cardio-respiratory fitness. In addition, average gray matter volume in the entorhinal cortex, bilaterally, was positively associated with memory performance. These data extend prior work on the cerebral effects of aerobic exercise and fitness to the entorhinal cortex in healthy young adults thus providing compelling evidence for a relationship between aerobic fitness and structure of the medial temporal lobe memory system. (C) 2015 Elsevier Inc. All rights reserved. C1 [Whiteman, Andrew S.; Stern, Chantal E.; Schon, Karin] Boston Univ, Dept Psychol & Brain Sci, 2 Cummington Mall, Boston, MA 02215 USA. [Whiteman, Andrew S.; Stern, Chantal E.; Schon, Karin] Boston Univ, Ctr Memory & Brain, 2 Cummington Mall, Boston, MA 02215 USA. [Young, Daniel E.] Univ Massachusetts, Coll Nursing & Hlth Sci, Exercise & Hlth Sci Program, 100 Morrissey Blvd, Boston, MA 02125 USA. [Budson, Andrew E.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Schon, Karin] Boston Univ, Sch Med, Dept Anat & Neurobiol, 72 East Concord St,L-1004, Boston, MA 02215 USA. [Schon, Karin] Boston Univ, Sch Med, Ctr Biomed Imaging, 650 Albany St, Boston, MA 02215 USA. [Budson, Andrew E.] VA Boston Healthcare Syst, 150 South Huntington St, Boston, MA 02130 USA. RP Schon, K (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, 72 East Concord St,L-1004, Boston, MA 02215 USA. EM asw221@bu.edu; daniel.young@umb.edu; abudson@bu.edu; chantal@bu.edu; kschon@bu.edu RI Meijer, Anna/K-5118-2016; OI Schon, Karin/0000-0003-2963-8449 FU Pathway to Independence Award [NIH K99AG036845, NIH R00AG036845]; Boston University Clinical and Translational Science Institute (CTSI) [UL1-TR000157]; Boston University Center for Biomedical Imaging (CBI); Boston University Undergraduate Research Opportunities Program FX This work was supported by a Pathway to Independence Award to K.S. (NIH K99AG036845 and NIH R00AG036845), the Boston University Clinical and Translational Science Institute (CTSI; UL1-TR000157), the Boston University Center for Biomedical Imaging (CBI), and a Student Research Award from the Boston University Undergraduate Research Opportunities Program to A.S.W. We would like to thank Drs. Xuemei He and Tai Chen for performing and overseeing the BDNF ELISAs, respectively, and the staff of the CTSI General Clinical Research Unit (GCRU) and of the CBI for their support. In addition, we would like to thank Dr. Neil Kowall for serving as the study physician for the GCRU, and Ms. Rachel Nauer for assistance with preparation of figures. NR 90 TC 4 Z9 4 U1 4 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2016 VL 126 BP 229 EP 238 DI 10.1016/j.neuroimage.2015.11.049 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DC5VX UT WOS:000369289800021 PM 26631814 ER PT J AU Schorge, JO AF Schorge, John O. TI Personalized Therapy in Action Evolving From a Series of One-Hit Wonders to a Paradigm With Staying Power SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID CANCER C1 [Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv, Boston, MA USA. RP Schorge, JO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv, Boston, MA USA. EM jschorge@partners.org NR 6 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 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2016 VL 127 IS 2 BP 202 EP 203 DI 10.1097/AOG.0000000000001278 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DC5IS UT WOS:000369255300003 PM 26942343 ER PT J AU Collins, L Ellis, M Pritchard, EWJ Jenkins, C Hoeritzauer, I Farquhar, A Laverty, O Murray, V Nelson, BD AF Collins, Lisa Ellis, Matthew Pritchard, Edward W. J. Jenkins, Christopher Hoeritzauer, Ingrid Farquhar, Adam Laverty, Orla Murray, Vincent Nelson, Brett D. TI Child-headed households in Rakai District, Uganda: a mixed-methods study SO PAEDIATRICS AND INTERNATIONAL CHILD HEALTH LA English DT Article DE Child-headed families; Uganda; HIV/AIDS ID COMMUNITY; AFRICA AB Objective: An important but neglected consequence of the AIDS pandemic that continues across sub-Saharan Africa is the phenomenon of child-headed households (CHH). This study aims to describe the challenges to health and well-being for young people living in child-headed households. Methods: A mixed-methods research approach linked common themes using qualitative and quantitative instruments to provide a broad picture of the location and challenges of CHH in Kabira, Kyotera and Kamuganja in the Rakai District of southern Uganda. Local knowledge was used to locate CHH. Results: 163 children living in 40 CHH were traced: 42.5% of the household heads were double orphans caring for younger siblings, and 43% were also caring for chronically ill or disabled grandparents who were economically unproductive and largely dependent on the eldest child for survival. It was found that those heading households were more likely not to attend school than children living at home with a parent. Their immediate needs ranged from food and shelter to health-care and education. Fear was a major theme: 38% of those interviewed reported fear of 'violence'. Children as young as 13 were responsible for navigating through complex decision-making processes from everyday basic necessities to decisions on the health care of younger siblings and grandparents. Conclusion: Children and young people living in CHH are a largely invisible and highly vulnerable population. Clear, officially accepted definitions of CHH are a first step in recognising this vulnerable group for whom safeguards will be necessary as social work develops in lower-and middle-income countries (LMICs). The precise numbers of CHH are unknown and further examination of this undocumented group is needed. C1 [Collins, Lisa; Ellis, Matthew; Pritchard, Edward W. J.] Univ Bristol, Sch Med, Bristol BS8 1TH, Avon, England. [Collins, Lisa; Nelson, Brett D.] Harvard Humanitarian Initiat, Boston, MA USA. [Ellis, Matthew] Univ Bristol, Sch Social & Community Med, Ctr Child & Adolescent Hlth, Bristol BS8 1TH, Avon, England. [Jenkins, Christopher; Hoeritzauer, Ingrid; Laverty, Orla] Natl Hlth Serv, London, England. [Jenkins, Christopher] Univ Nottingham, Nottingham NG7 2RD, England. [Farquhar, Adam; Murray, Vincent] Queens Univ Belfast, Belfast, Antrim, North Ireland. [Nelson, Brett D.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. RP Collins, L (reprint author), Manor Hall,Lower Clifton Hill, Bristol BS8 1BU, Avon, England. EM lisabridgetcollins@gmail.com OI Jenkins, Chris/0000-0003-3514-3581; Nelson, Brett/0000-0002-5049-1798 NR 23 TC 1 Z9 1 U1 1 U2 4 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 2046-9047 EI 2046-9055 J9 PAEDIATR INT CHILD H JI Paediatr. Int. Child Health PD FEB PY 2016 VL 36 IS 1 BP 58 EP 63 DI 10.1179/2046905514Y.0000000152 PG 6 WC Pediatrics SC Pediatrics GA DC9JW UT WOS:000369538800011 PM 26825224 ER PT J AU Akhbari, M Shamsollahi, MB Jutten, C Armoundas, AA Sayadi, O AF Akhbari, Mahsa Shamsollahi, Mohammad B. Jutten, Christian Armoundas, Antonis A. Sayadi, Omid TI ECG denoising and fiducial point extraction using an extended Kalman filtering framework with linear and nonlinear phase observations SO PHYSIOLOGICAL MEASUREMENT LA English DT Article DE electrocardiogram (ECG); extended Kalman filter (EKF); fiducial point extraction; denoising; dynamic time warping (DTW) ID HIDDEN MARKOV-MODELS; T-WAVE DELINEATION; DYNAMICAL MODEL; GIBBS SAMPLER; SIGNALS; ALGORITHMS; DATABASE AB In this paper we propose an efficient method for denoising and extracting fiducial point (FP) of ECG signals. The method is based on a nonlinear dynamic model which uses Gaussian functions to model ECG waveforms. For estimating the model parameters, we use an extended Kalman filter (EKF). In this framework called EKF25, all the parameters of Gaussian functions as well as the ECG waveforms (P-wave, QRS complex and T-wave) in the ECG dynamical model, are considered as state variables. In this paper, the dynamic time warping method is used to estimate the nonlinear ECG phase observation. We compare this new approach with linear phase observation models. Using linear and nonlinear EKF25 for ECG denoising and nonlinear EKF25 for fiducial point extraction and ECG interval analysis are the main contributions of this paper. Performance comparison with other EKF-based techniques shows that the proposed method results in higher output SNR with an average SNR improvement of 12 dB for an input SNR of -8 dB. To evaluate the FP extraction performance, we compare the proposed method with a method based on partially collapsed Gibbs sampler and an established EKF-based method. The mean absolute error and the root mean square error of all FPs, across all databases are 14 ms and 22 ms, respectively, for our proposed method, with an advantage when using a nonlinear phase observation. These errors are significantly smaller than errors obtained with other methods. For ECG interval analysis, with an absolute mean error and a root mean square error of about 22 ms and 29 ms, the proposed method achieves better accuracy and smaller variability with respect to other methods. C1 [Akhbari, Mahsa; Shamsollahi, Mohammad B.] Sharif Univ Technol, Dept Elect Engn, Biomed Signal & Image Proc Lab BiSIPL, Tehran, Iran. [Akhbari, Mahsa; Jutten, Christian] CNRS, Dept Images & Signals, GIPSA Lab, F-75700 Paris, France. [Akhbari, Mahsa; Jutten, Christian] Univ Grenoble Alpes, St Martin Dheres, France. [Armoundas, Antonis A.; Sayadi, Omid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Akhbari, M; Shamsollahi, MB (reprint author), Sharif Univ Technol, Dept Elect Engn, Biomed Signal & Image Proc Lab BiSIPL, Tehran, Iran.; Akhbari, M; Jutten, C (reprint author), CNRS, Dept Images & Signals, GIPSA Lab, F-75700 Paris, France.; Akhbari, M; Jutten, C (reprint author), Univ Grenoble Alpes, St Martin Dheres, France.; Armoundas, AA; Sayadi, O (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM mahsa_akhbari@yahoo.com; mbshams@sharif.edu; christian.jutten@gipsa-lab.grenoble-inp.fr; aarmoundas@partners.org; sayadi.omid@mgh.harvard.edu FU French Embassy; [ERC-2012-AdG-320684-CHESS] FX This work has been partly supported by the PhD scholarship of French Embassy and the European project ERC-2012-AdG-320684-CHESS. NR 47 TC 4 Z9 4 U1 4 U2 11 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0967-3334 EI 1361-6579 J9 PHYSIOL MEAS JI Physiol. Meas. PD FEB PY 2016 VL 37 IS 2 BP 203 EP 226 DI 10.1088/0967-3334/37/2/203 PG 24 WC Biophysics; Engineering, Biomedical; Physiology SC Biophysics; Engineering; Physiology GA DC6WC UT WOS:000369359300003 PM 26767425 ER PT J AU Sheu, EG Channick, R Gee, DW AF Sheu, Eric G. Channick, Richard Gee, Denise W. TI Improvement in severe pulmonary hypertension in obese patients after laparoscopic gastric bypass or sleeve gastrectomy SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Bariatric; Obesity; Pulmonary (lungs); Cardio; Clinical papers/trials/research ID BARIATRIC SURGERY; ARTERIAL-HYPERTENSION; OUTCOMES AB Case reports have suggested that bariatric surgery improves pulmonary hypertension. We performed a retrospective, case-control study to evaluate the safety and efficacy of bariatric surgery in obese patients with severe pulmonary hypertension. Morbidly obese patients followed in a specialty pulmonary hypertension clinic who underwent laparoscopic gastric bypass or sleeve gastrectomy between 2008 and 2013 (n = 10) were compared to a BMI-matched cohort managed with maximal medical therapy (n = 10). Patients with advanced malignancy, prior heart/lung transplantation, and pulmonary hypertension from thromboembolism were excluded. Primary outcomes assessed were changes in use of pulmonary vasodilatory and diuretic medications, need for home oxygen therapy, and mean pulmonary arterial pressures. Secondary outcomes measured were excess body weight loss, perioperative mortality and morbidity, and hospital length of stay. More patients who underwent bariatric surgery experienced improvements in pulmonary arterial pressures (75 vs. 0 %, p = 0.02), reduction in or discontinuation of pulmonary vasodilatory therapy (67 vs. 0 %, p = 0.01), and decreased diuretic requirements (86 vs. 13 %, p = 0.01) than the control cohort. Seventy-five percent of patients previously on home oxygen discontinued therapy after surgery, while oxygen requirements increased in 50 % of the control cohort. Excess body weight loss was greater in the surgical group (EWL 68 vs. 19 %, p < 0.001). Seven significant complications in five patients occurred in the first postoperative year, but there were no mortalities. Mean inpatient length of stay was 5 days. Laparoscopic gastric bypass and sleeve gastrectomy in obese patients improves pulmonary hypertension in the short term. C1 [Sheu, Eric G.] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. [Channick, Richard] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gee, Denise W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sheu, Eric G.; Channick, Richard; Gee, Denise W.] Harvard Univ, Sch Med, Boston, MA USA. RP Sheu, EG (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.; Sheu, EG (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM esheu@partners.org NR 12 TC 3 Z9 3 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD FEB PY 2016 VL 30 IS 2 BP 633 EP 637 DI 10.1007/s00464-015-4251-5 PG 5 WC Surgery SC Surgery GA DC6NE UT WOS:000369335900031 PM 26091991 ER PT J AU Vergallo, R Aguirre, AD Abtahian, F Minami, Y Soeda, T Chatzizisis, YS Croce, K Jang, IK AF Vergallo, Rocco Aguirre, Aaron D. Abtahian, Farhad Minami, Yoshiyasu Soeda, Tsunenari Chatzizisis, Yiannis S. Croce, Kevin Jang, Ik-Kyung TI Recurrent myocardial infarctions and premature coronary atherosclerosis in a 23-year-old man with antiphospholipid syndrome SO THROMBOSIS AND HAEMOSTASIS LA English DT Editorial Material C1 [Vergallo, Rocco; Abtahian, Farhad; Minami, Yoshiyasu; Soeda, Tsunenari; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Aguirre, Aaron D.; Chatzizisis, Yiannis S.; Croce, Kevin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Jang, Ik-Kyung] Kyung Hee Univ, Div Cardiol, Seoul, South Korea. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@mgh.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 3 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD FEB PY 2016 VL 115 IS 2 BP 237 EP 239 DI 10.1160/TH15-05-0412 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DC7WP UT WOS:000369431700003 PM 26423215 ER PT J AU Chen, YF Sadow, PM Suh, H Lee, KE Choi, JY Suh, YJ Wang, TS Lubitz, CC AF Chen, Yufei Sadow, Peter M. Suh, Hyunsuk Lee, Kyu Eun Choi, June Young Suh, Yong Joon Wang, Tracy S. Lubitz, Carrie C. TI BRAF(V600E) Is Correlated with Recurrence of Papillary Thyroid Microcarcinoma: A Systematic Review, Multi-Institutional Primary Data Analysis, and Meta-Analysis SO THYROID LA English DT Article ID BRAF V600E MUTATION; UNITED-STATES; FOLLOW-UP; INCREASING INCIDENCE; PROGNOSTIC-FACTORS; CANCER; CARCINOMA; ASSOCIATION; OUTCOMES; RISK AB Background: Given the increasing incidence of papillary thyroid carcinoma despite stable disease-specific mortality rates, the potential for the disease to reoccur is a key outcome to predict. The BRAF(V600E) mutation has been associated with recurrent disease in larger tumors. However, its correlation in papillary thyroid microcarcinoma (PTMC) is not clear in individual series. Methods: The MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for studies including patients with PTMC undergoing initial surgical treatment. Studies with at least two years of follow-up, BRAF genotyping (the comparator), and recurrence as an outcome were included, as were unpublished primary data on 485 patients from two institutions. The metameter analyzed was odds ratio (OR) for recurrence between patients with BRAF(V600E) versus BRAF wild type (BRAFwt). Results: The initial search identified 431 references. After screening of the abstracts for inclusion, 44 manuscripts were reviewed in full by two independent reviewers. Four published studies and primary data from two institutional cohorts were included in the final analysis. A meta-analysis of 2247 PTMC patients revealed that patients with a BRAF(V600E) mutation had a higher likelihood for recurrence (odds ratio 2.09 [confidence interval 1.31-3.33], p=0.002). Conclusions: This meta-analysis shows that BRAF mutational status correlates with recurrence of PTMCs, highlighting the potential utility of genotyping in preoperative and postoperative planning. BRAF mutation may be helpful in risk-stratifying patients with PTMC for surgical management versus observation. C1 [Chen, Yufei; Lubitz, Carrie C.] Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Suh, Hyunsuk] Mt Sinai Med Ctr, Dept Surg, Box 1259, New York, NY 10029 USA. [Lee, Kyu Eun; Choi, June Young; Suh, Yong Joon] Seoul Natl Univ Hosp, Dept Surg, Seoul 110744, South Korea. [Lee, Kyu Eun; Choi, June Young; Suh, Yong Joon] Coll Med, Seoul, South Korea. [Wang, Tracy S.] Med Coll Wisconsin, Dept Surg, 8700 W Wisconsin Ave, Milwaukee, WI 53226 USA. [Lubitz, Carrie C.] Inst Technol Assessment, Boston, MA USA. RP Chen, YF (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA. EM ychen49@partners.org NR 43 TC 5 Z9 7 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD FEB 1 PY 2016 VL 26 IS 2 BP 248 EP 255 DI 10.1089/thy.2015.0391 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DC8YO UT WOS:000369506700009 PM 26671072 ER PT J AU Kitahara, CM McCullough, ML Franceschi, S Rinaldi, S Wolk, A Neta, G Adami, HO Anderson, K Andreotti, G Freeman, LEB Bernstein, L Buring, JE Clavel-Chapelon, F De Roo, LA Gao, YT Gaziano, JM Giles, GG Hakansson, N Horn-Ross, PL Kirsh, VA Linet, MS Maclnnis, RJ Orsini, N Park, Y Patel, AV Purdue, MP Riboli, E Robien, K Rohan, T Sandler, DP Schairer, C Schneider, AB Sesso, HD Shu, XO Singh, PN van den Brandt, PA Ward, E Weiderpass, E White, E Xiang, YB Zeleniuch-Jacquotte, A Zheng, W Hartge, P de Gonzalez, AB AF Kitahara, Cari M. McCullough, Marjorie L. Franceschi, Silvia Rinaldi, Sabina Wolk, Alicja Neta, Gila Adami, Hans Olov Anderson, Kristin Andreotti, Gabriella Freeman, Laura E. Beane Bernstein, Leslie Buring, Julie E. Clavel-Chapelon, Francoise De Roo, Lisa A. Gao, Yu-Tang Gaziano, J. Michael Giles, Graham G. Hakansson, Niclas Horn-Ross, Pamela L. Kirsh, Vicki A. Linet, Martha S. Maclnnis, Robert J. Orsini, Nicola Park, Yikyung Patel, Alpa V. Purdue, Mark P. Riboli, Elio Robien, Kimberly Rohan, Thomas Sandler, Dale P. Schairer, Catherine Schneider, Arthur B. Sesso, Howard D. Shu, Xiao-Ou Singh, Pramil N. van den Brandt, Piet A. Ward, Elizabeth Weiderpass, Elisabete White, Emily Xiang, Yong-Bing Zeleniuch-Jacquotte, Anne Zheng, Wei Hartge, Patricia de Gonzalez, Amy Berrington TI Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype: Pooled Analysis of 22 Prospective Studies SO THYROID LA English DT Article ID BASE-LINE CHARACTERISTICS; BODY-MASS INDEX; NIH-AARP DIET; UNITED-STATES; BREAST-CANCER; LARGE COHORT; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; FAT DISTRIBUTION; LIFE-STYLE AB Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5cm)=1.07 [1.04-1.10], BMI (per 5kg/m(2))=1.06 [1.02-1.10], waist circumference (per 5cm)=1.03 [1.01-1.05], young-adult BMI (per 5kg/m(2))=1.13 [1.02-1.25], and adulthood BMI gain (per 5kg/m(2))=1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p=0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies. C1 [Kitahara, Cari M.; Andreotti, Gabriella; Freeman, Laura E. Beane; Linet, Martha S.; Schairer, Catherine; Hartge, Patricia; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [McCullough, Marjorie L.; Patel, Alpa V.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Franceschi, Silvia; Rinaldi, Sabina] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France. [Wolk, Alicja; Hakansson, Niclas; Orsini, Nicola] Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, S-10401 Stockholm, Sweden. [Neta, Gila] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Adami, Hans Olov] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Adami, Hans Olov; Buring, Julie E.; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Anderson, Kristin] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Anderson, Kristin] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Clavel-Chapelon, Francoise] Ctr Res Epidemiol & Populat Hlth CESP, INSERM, U1018, Villejuif, France. [Clavel-Chapelon, Francoise] France Paris South Univ, INSERM, UMRS 1018, Team 9, Villejuif, France. [De Roo, Lisa A.] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. [De Roo, Lisa A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Gao, Yu-Tang] Shanghai Jiao Tong Univ, Sch Med, Dept Epidemiol, Shanghai Canc Inst,Renji Hosp, Shanghai, Peoples R China. [Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02115 USA. [Gaziano, J. Michael] Massachusetts Vet Epidemiol Res & Informat Ctr, Geriatric Res Educ & Clin Ctr, VA Boston Healthcare Syst, Boston, MA USA. [Giles, Graham G.; Maclnnis, Robert J.] Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic, Australia. [Giles, Graham G.; Maclnnis, Robert J.] Univ Melbourne, Ctr Biostat & Epidemiol, Melbourne Sch Populat & Global Hlth, Carlton, Vic 3053, Australia. [Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA USA. [Kirsh, Vicki A.] Canc Care Ontario, Prevent & Canc Control, Toronto, ON, Canada. [Kirsh, Vicki A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Park, Yikyung] Washington Univ, Div Publ Hlth Sci, Sch Med, St Louis, MO USA. [Purdue, Mark P.] Ontario Inst Canc Res, Toronto, ON, Canada. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Imperial Sch Publ Hlth, London, England. [Robien, Kimberly] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Exercise & Nutr Sci, Washington, DC USA. [Rohan, Thomas] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Schneider, Arthur B.] Univ Illinois, Sect Endocrinol Diabet & Metab, Chicago, IL USA. [Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Div Epidemiol,Dept Med, Nashville, TN 37212 USA. [Singh, Pramil N.] Loma Linda Univ, Sch Publ Hlth, Ctr Hlth Res, Loma Linda, CA 92350 USA. [van den Brandt, Piet A.] Maastricht Univ, Dept Epidemiol, GROW Sch Oncol & Dev Biol, NL-6200 MD Maastricht, Netherlands. [Ward, Elizabeth] Amer Canc Soc, Intramural Res, Atlanta, GA 30329 USA. [Weiderpass, Elisabete] Univ Tromso, Dept Community Med, Fac Hlth Sci, Arctic Univ Norway, Tromso, Norway. [Weiderpass, Elisabete] Canc Registry Norway, Inst Populat Based Canc Res, Dept Res, Oslo, Norway. [Weiderpass, Elisabete] Folkalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland. [White, Emily] Fred Hutchinson Canc Res Ctr, Publ Hlth Serv Div, 1124 Columbia St, Seattle, WA 98104 USA. [White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Div Epidemiol, Dept Populat Hlth, New York, NY USA. [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Inst Canc, New York, NY USA. RP Kitahara, CM (reprint author), Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 7E 536, Bethesda, MD 20892 USA. EM kitaharac@mail.nih.gov RI Purdue, Mark/C-9228-2016; Weiderpass, Elisabete/M-4029-2016; CLAVEL, Christine/P-6333-2016; Zheng, Wei/O-3351-2013; Beane Freeman, Laura/C-4468-2015; Kitahara, Cari/R-8267-2016; OI Purdue, Mark/0000-0003-1177-3108; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Weiderpass, Elisabete/0000-0003-2237-0128; Zheng, Wei/0000-0003-1226-070X; Beane Freeman, Laura/0000-0003-1294-4124; Robien, Kim/0000-0002-2120-2280; Sandler, Dale/0000-0002-6776-0018 FU Swedish Research Council; Swedish Cancer Foundation; Karolinska Institutet, Stockholm, Sweden; American Cancer Society; National Cancer Institute [R01 CA77398, R01 CA39742, CA-34933, CA-40360, CA-097193, R37 CA070867, UM1 CA182910, R01 CA082729, UM1 CA173640, K05-CA154337]; California Department of Public Health (CDPH) [103885]; NCI's SEER program [HHSN261201000140C, HHSN261201000035C, HHSN261201000034C]; Centers for Disease Control and Prevention's (CDCP) National Program of Cancer Registries [U58DP003862-01]; World Cancer Research Fund [2009/92]; European Commission (DG-SANCO); International Agency for Research on Cancer; Danish Cancer Society, Denmark; Ligue Contre le Cancer, France; Institut Gustave Roussy, France; Mutuelle Generale de l'Education Nationale, France; Institut National de la Sante et de la Recherche Medicale, France; Deutsche Krebshilfe, Germany; Deutsches Krebsforschungszentrum; Federal Ministry of Education and Research, Germany; Hellenic Health Foundation, Greece; Italian Association for Research on Cancer; National Research Council, Italy; Dutch Ministry of Public Health, Welfare and Sports, the Netherlands; Netherlands Cancer Registry, the Netherlands; LK Research Funds, the Netherlands; Dutch Prevention Funds, the Netherlands; Dutch ZON (Zorg Onderzoek Nederland), the Netherlands; World Cancer Research Fund, London, UK; Statistics Netherlands, the Netherlands; European Research Council, Norway; Health Research Fund; Regional Government of Andalucia [6236]; Regional Government of Asturias [6236]; Regional Government of Basque Country [6236]; Regional Government of Murcia [6236]; Navarra, ISCIII RETIC, Spain [RD06/0020/0091]; Swedish Cancer Society, Sweden; Swedish Scientific Council, Sweden; Regional Government of Skane; Vasterbotten, Sweden; Cancer Research United Kingdom; Medical Research Council, United Kingdom; Stroke Association, United Kingdom; British Heart Foundation, United Kingdom; Department of Health, Food Standards Agency, United Kingdom; Wellcome Trust; French National Cancer Institute (L'Institut National du Cancer; INCA) [2009-139]; Ligue contre le Cancer (France); Institut Gustave Roussy (France); Mutuelle Generale de l'Education Nationale (France); Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health (RTICC) [DR06/0020/0091]; regional government from Asturias; regional government from Andalucia; regional government from Murcia; regional government from Navarra; regional government from Vasco Country; Catalan Institute of Oncology of Spain; Cancer Research UK; Medical Research Council, UK; Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food Standards Agency, UK; Wellcome Trust, UK; Hellenic Health Foundation; Compagnia San Paolo, Italy; Dutch Ministry of Public Health, Welfare and Sports; Dutch Ministry of Health; Dutch Prevention Funds; LK Research Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands); Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Nordforsk-Centre of Excellence programme; National Health and Medical Research Council of Australia [209057, 251533]; National Heart, Lung, and Blood Institute [HL-26490, HL-34595]; National Institutes of Health, Bethesda, MD; NIH, National Institute of Environmental Health Sciences [ZO1-ES-044005]; Office of Dietary Supplements [K05-CA154337] FX COSM and SMC: These cohorts are supported by the Swedish Research Council, the Swedish Cancer Foundation, and by Strategic Funds from Karolinska Institutet, Stockholm, Sweden.; CPS-II: The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II (CPS-II) cohort.; CTS: The CTS is supported by grant R01 CA77398 from the National Cancer Institute. The collection of cancer incidence data used in the CTS is supported by the California Department of Public Health (CDPH) as part of the state-wide cancer reporting program mandated by California Health and Safety Code Section 103885; the NCI's SEER program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's (CDCP) National Program of Cancer Registries, under agreement U58DP003862-01 awarded to the CDPH. The ideas and opinions expressed herein are those of the author(s) and endorsement by the CDPH, NCI, and CDCP or their contractors and subcontractors is not intended nor should be inferred.; EPIC: The authors are grateful to the support of the World Cancer Research Fund (2009/92). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society, Denmark; Ligue Contre le Cancer, France; Institut Gustave Roussy, France; Mutuelle Generale de l'Education Nationale, France; Institut National de la Sante et de la Recherche Medicale, France; Deutsche Krebshilfe, Germany, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research, Germany; Hellenic Health Foundation, Greece; Italian Association for Research on Cancer; National Research Council, Italy; Dutch Ministry of Public Health, Welfare and Sports, the Netherlands; Netherlands Cancer Registry, the Netherlands; LK Research Funds, the Netherlands; Dutch Prevention Funds, the Netherlands; Dutch ZON (Zorg Onderzoek Nederland), the Netherlands; World Cancer Research Fund, London, UK; Statistics Netherlands, the Netherlands; European Research Council, Norway; Health Research Fund, Regional Governments of Andalucia, Asturias, Basque Country, Murcia (project no. 6236) and Navarra, ISCIII RETIC (RD06/0020/0091), Spain; Swedish Cancer Society, Sweden; Swedish Scientific Council, Sweden; Regional Government of Skane and Vasterbotten, Sweden; Cancer Research United Kingdom; Medical Research Council, United Kingdom; Stroke Association, United Kingdom, British Heart Foundation, United Kingdom; Department of Health, Food Standards Agency, United Kingdom; and Wellcome Trust; United Kingdom. We thank Bertrand Hemon for his precious help with the EPIC database. The principle investigators and funders corresponding to each of the EPIC centers that contributed cases were Kim Overvad, Anne Tjonneland (Denmark); Francoise Clavel-Chapelon (France); Heiner Boeing, Rudolf Kaaks (Germany); Antonia Trichopoulou (Greece); Vittorio Krogh, Domenico Palli, Paolo Vineis, Salvatore Panico, Rosario Tumino (Italy); Eiliv Lund (Norway); Antonio Agudo, Maria Jose Sanchez, J. Ramon Quiros, Carmen Navarro, Aurelio Barricarte, Miren Dorronsoro (Spain); Mattias Johansson, Jonas Manjer (Sweden); H. Bas Bueno-de-Mesquita, Petra H. Peeters (The Netherlands); Timothy Key, Nick Wareham (UK); The coordination of European Prospective Investigation into Cancer and Nutrition is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer.; The national cohorts are supported by the French National Cancer Institute (L'Institut National du Cancer; INCA); Grant Number: 2009-139; Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health (RTICC (DR06/0020/0091); the participating regional governments from Asturias, Andalucia, Murcia, Navarra and Vasco Country and the Catalan Institute of Oncology of Spain; Cancer Research UK; Medical Research Council, UK; the Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food Standards Agency, UK; the Wellcome Trust, UK; the Hellenic Health Foundation; Italian Association for Research on Cancer; Compagnia San Paolo, Italy; Dutch Ministry of Public Health, Welfare and Sports; Dutch Ministry of Health; Dutch Prevention Funds; LK Research Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands); Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Nordforsk-Centre of Excellence programme.; IWHS: The authors thank the study participants. IWHS is funded by a grant from the National Cancer Institute (R01 CA39742).; Melbourne Collaborative Cohort Study: This study was made possible by the contribution of many people, including the original investigators and the diligent team who recruited the participants and who continue working on follow-up. We would also like to express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. This work was supported by infrastructure from Cancer Council Victoria and grants from the National Health and Medical Research Council of Australia 209057 and 251533.; PHS: This study is supported by grants from the National Cancer Institute (CA-34933, CA-40360, and CA-097193) and from the National Heart, Lung, and Blood Institute (HL-26490 and HL-34595), National Institutes of Health, Bethesda, MD.; The Sister Study is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZO1-ES-044005). Support for data collection and study and data management are provided by Social & Scientific Systems, Inc., and Westat, Inc., Durham, NC. Aimee D'Aloisio, Sandra Halverson, Dan Scharf, and David Shore helped prepare the data for this analysis.; The SWHS and SMHS are supported in part by research grants from the National Cancer Institute (R37 CA070867, UM1 CA182910, R01 CA082729, and UM1 CA173640). The authors thank participants and research staff members of the studies for their contribution.; USRT: The authors thank the study participants and Jerry Reid of the American Registry of Radiologic Technologists for their continued support of this study; Diane Kampa and Allison Iwan of the University of Minnesota for study management and data collection; and Jeremy Miller at Information Management Services, Inc., for biomedical computing support.; VITAL: Emily White was supported by the grant K05-CA154337 (National Cancer Institute and Office of Dietary Supplements). NR 63 TC 3 Z9 3 U1 2 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD FEB 1 PY 2016 VL 26 IS 2 BP 306 EP 318 DI 10.1089/thy.2015.0319 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DC8YO UT WOS:000369506700016 PM 26756356 ER PT J AU Charness, ME Riley, EP Sowell, ER AF Charness, Michael E. Riley, Edward P. Sowell, Elizabeth R. TI Drinking During Pregnancy and the Developinc Brain: Is Any Amount Safe? SO TRENDS IN COGNITIVE SCIENCES LA English DT Editorial Material ID ALCOHOL SPECTRUM DISORDERS; EXPOSURE; MODERATE; MOTHERS C1 [Charness, Michael E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. [Charness, Michael E.] Harvard Univ, Sch Med, Dept Neurol, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. [Charness, Michael E.] Boston Univ, Sch Med, Dept Neurol, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. [Riley, Edward P.] San Diego State Univ, Ctr Behav Teratol, 6330 Alvarado Court, San Diego, CA 92120 USA. [Sowell, Elizabeth R.] Univ So Calif, Keck Sch Med, Inst Dev Mind, Childrens Hosp Los Angeles,Dev Cognit Neuroimagin, Los Angeles, CA 90027 USA. [Sowell, Elizabeth R.] Univ So Calif, Keck Sch Med, Inst Dev Mind, Childrens Hosp Los Angeles,Dept Pediat, Los Angeles, CA 90027 USA. RP Charness, ME (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.; Charness, ME (reprint author), Harvard Univ, Sch Med, Dept Neurol, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.; Charness, ME (reprint author), Boston Univ, Sch Med, Dept Neurol, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.; Sowell, ER (reprint author), Univ So Calif, Keck Sch Med, Inst Dev Mind, Childrens Hosp Los Angeles,Dev Cognit Neuroimagin, Los Angeles, CA 90027 USA.; Sowell, ER (reprint author), Univ So Calif, Keck Sch Med, Inst Dev Mind, Childrens Hosp Los Angeles,Dept Pediat, Los Angeles, CA 90027 USA. EM mcharness@hms.harvard.edu FU NIAAA [AA12974, AA014811, AA017122]; VA Merit Review [5101BX002374] FX The work of the authors is supported by NIAAA grants AA12974, AA014811, AA017122, and VA Merit Review 5101BX002374. NR 15 TC 2 Z9 2 U1 1 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD FEB PY 2016 VL 20 IS 2 BP 80 EP 82 DI 10.1016/j.tics.2015.09.011 PG 3 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA DC8MJ UT WOS:000369473400004 PM 26801950 ER PT J AU Chanes, L Barrett, LF AF Chanes, Lorena Barrett, Lisa Feldman TI Redefining the Role of Limbic Areas in Cortical Processing SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID SUPERIOR TEMPORAL SULCUS; OLD-WORLD MONKEY; RHESUS-MONKEY; HUMAN BRAIN; PREFRONTAL CORTEX; CORTICOCORTICAL CONNECTIONS; PIRIFORM CORTEX; RESTING-STATE; INTEROCEPTIVE INFERENCE; FUNCTIONAL NETWORKS AB There is increasing evidence that the brain actively constructs action and perception using past experience. In this paper, we propose that the direction of information flow along gradients of laminar differentiation provides important insight on the role of limbic cortices in cortical processing. Cortical limbic areas, with a simple laminar structure (e.g., no or rudimentary layer IV), send 'feedback' projections to lower level better laminated areas. We propose that this 'feedback' functions as predictions that drive processing throughout the cerebral cortex. This hypothesis has the potential to provide a unifying framework for an increasing number of proposals that use predictive coding to explain a myriad of neural processes and disorders, and has important implications for hypotheses about consciousness. C1 [Chanes, Lorena; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Chanes, Lorena; Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Chanes, Lorena; Barrett, Lisa Feldman] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, Boston, MA 02115 USA.; Barrett, LF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.; Barrett, LF (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM l.barrett@neu.edu FU US National Institute on Aging grant [R01AG030311]; US National Institute of Child Health and Human Development grant [R21 HD076164]; US Army Research Institute for the Behavioral and Social Sciences [W5J9CQ1200049, W5J9CQ1100046]; Fyssen Foundation FX The authors thank M.A. Garcia-Cabezas for helpful discussions, thoughtful feedback on earlier versions of this manuscript, and preparation of Figure I in Box 2. We also thank T. Cleland for guidance on predictive coding account of olfactory and gustatory systems. This work was supported by a US National Institute on Aging grant (R01AG030311), a US National Institute of Child Health and Human Development grant (R21 HD076164), and contracts from the US Army Research Institute for the Behavioral and Social Sciences (contracts W5J9CQ1200049 and W5J9CQ1100046) to L.F.B., as well as a Fyssen Foundation postdoctoral fellowship to L.C. NR 112 TC 12 Z9 12 U1 5 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD FEB PY 2016 VL 20 IS 2 BP 96 EP 106 DI 10.1016/j.tics.2015.11.005 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA DC8MJ UT WOS:000369473400008 PM 26704857 ER PT J AU Mao, Y Hedgire, SS Liao, G Lv, FJ Li, YM Li, Q Wang, ZW AF Mao, Yun Hedgire, Sandeep S. Liao, Gang Lv, Fajin Li, Yongmei Li, Qi Wang, Ziwei TI Topographic distribution and characteristics of normal gastric regional lymph nodes on diffusion-weighted magnetic resonance imaging SO ACTA RADIOLOGICA LA English DT Article DE Gastric cancer; lymph node; magnetic resonance imaging (MRI); diffusion-weighted imaging (DWI); apparent diffusion coefficient (ADC) ID MULTIDETECTOR ROW CT; CERVICAL-CANCER; METASTASES; DISCRIMINATION; COEFFICIENT; CARCINOMA AB Background: Current lack of recognition of normal gastric regional lymph nodes (GRLNs) and inherent defect of morphological imaging limit the accuracy of preoperative nodal (N) staging of gastric cancer. Purpose: To map the distribution of normal GRLNs and evaluating the characteristics of GRLNs with diffusion-weighted imaging (DWI) in healthy population. Material and Methods: Forty-nine enrolled healthy volunteers were divided into two age groups and underwent conventional magnetic resonance imaging (MRI) and DWI examinations. The characteristics of GRLNs in 14 regional stations, including short axis diameter (SD), short-to-long axis diameter ratio (SLR), signal-to-noise ratio (SNR), contrast- to-noise ratio (CNR), and apparent diffusion coefficient (ADC), were recorded and compared between age groups and among different stations. Results: The normal GRLNs were mainly distributed in station 7 in both age groups, followed by stations 3, 8, and 9. The SLR was lower in the young group than in the old group (P=0.034) while SD, SNR, CNR, and ADC were significantly higher in the young group compared to the old group, P=0.045, 0.041, 0.037, and 0.042, respectively. SD was different among stations in both age groups (P=0.002, 0.001), especially bigger in station 8, and the SNRs and CNRs of stations 8 and 9 were relatively high in the old group (P=0.031, 0.035), while there was no difference in ADC value. Conclusion: Better understanding of the appearances of normal GRLNs on conventional MRI and DWI may help to build more appropriate imaging criteria for GRLN assessment in gastric cancer. C1 [Mao, Yun; Liao, Gang; Lv, Fajin; Li, Yongmei; Li, Qi; Wang, Ziwei] Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China. [Hedgire, Sandeep S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA USA. RP Wang, ZW (reprint author), Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China. EM maoyun1979@163.com NR 23 TC 0 Z9 0 U1 2 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0284-1851 EI 1600-0455 J9 ACTA RADIOL JI Acta Radiol. PD FEB PY 2016 VL 57 IS 2 BP 152 EP 161 DI 10.1177/0284185115574736 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DC0LT UT WOS:000368909500006 PM 25735622 ER PT J AU Sidani, JE Shensa, A Shiffman, S Switzer, GE Primack, BA AF Sidani, Jaime E. Shensa, Ariel Shiffman, Saul Switzer, Galen E. Primack, Brian A. TI Behavioral associations with waterpipe tobacco smoking dependence among US young adults SO ADDICTION LA English DT Article DE Addiction; dependence; hookah; measurement; scale; tobacco; waterpipe ID HOOKAH SMOKING; UNITED-STATES; UNIVERSITY-STUDENTS; CIGARETTE-SMOKING; NICOTINE EXPOSURE; PUFF TOPOGRAPHY; SMOKERS; PREVALENCE; ATTITUDES; ADDICTION AB Background and AimsWaterpipe tobacco smoking (WTS) is increasingly prevalent in the United States, especially among young adults. We aimed to (1) adapt items from established dependence measures into a WTS dependence scale for US young adults (the US Waterpipe Dependence Scale), (2) determine the factor structure of the items and (3) assess associations between scale values and behavioral use characteristics known to be linked to dependence. DesignCross-sectional survey. SettingUnited States. ParticipantsA total of 436 past-year waterpipe tobacco users ages 18-30years selected at random from a national probability-based panel. MeasurementsParticipants responded to six tobacco dependence items adapted for WTS in US populations. Behavioral use characteristics included factors such as frequency of use and age of initiation. FindingsPrincipal components analysis yielded an unambiguous one-factor solution. Approximately half (52.9%) of past-year waterpipe tobacco users received a score of 0, indicating that none of the six WTS dependence items were endorsed. Approximately one-quarter (25.4%) endorsed one dependence item and 22.7% endorsed two or more items. Higher WTS dependence scores were associated significantly with all five behavioral use characteristics. For example, compared with those who endorsed no dependence items, those who endorsed two or more had an adjusted odds ratio (AOR) of 3.90 [95% confidence interval (CI)=1.56-9.78] for having had earlier age of initiation and an AOR of 32.75 (95% CI=9.76-109.86) for more frequent WTS sessions. ConclusionsScores on a six-item waterpipe tobacco smoking dependence scale (the US Waterpipe Dependence Scale) correlate with measures that would be expected to be related to dependence, such as amount used and age of initiation. C1 [Sidani, Jaime E.; Shensa, Ariel; Primack, Brian A.] Univ Pittsburgh, Sch Med, Dept Med, UPMCMontefiore Hosp,Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Sidani, Jaime E.; Shensa, Ariel; Primack, Brian A.] Univ Pittsburgh, Ctr Res Media Technol & Hlth, Pittsburgh, PA USA. [Shiffman, Saul] Pinney Associates, Pittsburgh, PA USA. [Switzer, Galen E.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Psychiat Med, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Clin, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Translat Sci, Pittsburgh, PA USA. [Primack, Brian A.] Univ Pittsburgh, Dept Pediat, Sch Med, Div Adolescent Med, 3420 Fifth Ave, Pittsburgh, PA 15260 USA. RP Sidani, JE (reprint author), Ctr Res Media Technol & Hlth, 230 McKee Pl Suite 600, Pittsburgh, PA 15213 USA. EM sidanije@upmc.edu FU National Cancer Institute at the National Institutes of Health [R01-CA140150]; Steven Manners Memorial Fund at the University of Pittsburgh Center for Social and Urban Research FX This work was supported by the National Cancer Institute at the National Institutes of Health (R01-CA140150) and the Steven Manners Memorial Fund at the University of Pittsburgh Center for Social and Urban Research, both awarded to B.A.P. The funding agencies 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. NR 44 TC 3 Z9 3 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD FEB PY 2016 VL 111 IS 2 BP 351 EP 359 DI 10.1111/add.13163 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DC0XE UT WOS:000368940500020 PM 26417942 ER PT J AU Pursnani, A Celeng, C Schlett, CL Maythofer, T Zakroysky, P Lee, H Ferencik, M Fleg, JL Bamberg, F Wiviott, SD Truong, QA Udelson, JE Nagurney, JT Hoffmann, U AF Pursnani, Amit Celeng, Csilla Schlett, Christopher L. Maythofer, Thomas Zakroysky, Pearl Lee, Hang Ferencik, Maros Fleg, Jerome L. Bamberg, Fabian Wiviott, Stephen D. Truong, Quynh A. Udelson, James E. Nagurney, John T. Hoffmann, Udo TI Use of Coronary Computed Tomographic Angiography Findings to Modify Statin and Aspirin Prescription in Patients With Acute Chest Pain SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID INTERNATIONAL MULTICENTER REGISTRY; ARTERY-DISEASE; PROGNOSTIC VALUE; CT ANGIOGRAPHY; EMERGENCY-DEPARTMENT; SYMPTOMATIC PATIENTS; CLINICAL-OUTCOMES; RISK-FACTORS; ATHEROSCLEROSIS; METAANALYSIS AB Coronary CT angiography (CCTA) is used in patients with low-intermediate chest pain presenting to the emergency department for its reliability in excluding acute coronary syndrome (ACS). However, its influence on medication modification in this setting is unclear. We sought to determine whether knowledge of CCTA-based coronary artery disease (CAD) was associated with change in statin and aspirin prescription. We used the CCTA arm of the Rule Out Myocardial Infarction using Computed Angiographic Tomography II multicenter, randomized control trial (R-II) and comparison cohort from the observational Rule Out Myocardial Infarction using Computed Angiographic Tomography I cohort (R-I). In R-II, subjects were randomly assigned to CCTA to guide decision making, whereas in R-I patients underwent CCTA with results blinded to caregivers and managed according to standard care. Our final cohort consisted of 277 subjects from R-I and 370 from R-II. ACS rate was similar (6.9% vs 6.2% respectively, p = 0.75). For subjects with CCTA-detected obstructive CAD without ACS, initiation of statin was significantly greater after disclosure of CCTA results (0% in R-I vs 20% in R-II, p = 0.009). Conversely, for subjects without CCTA-detected. CAD, aspirin prescription was lower with disclosure of CCTA results (16% in R-I vs 4.8% in R-II, p = 0.001). However, only 68% of subjects in R-II with obstructive CAD were discharged on statin and 65% on aspirin. In conclusion, physician knowledge of CCTA results leads to improved alignment of aspirin and statin with the presence and severity of CAD although still many patients with CCTA-detected CAD are not discharged on aspirin or statin. Our findings suggest opportunity for practice improvement when CCTA is performed in the emergency department. (C) 2016 Elsevier Inc. All rights reserved. C1 [Pursnani, Amit; Celeng, Csilla; Maythofer, Thomas; Ferencik, Maros; Truong, Quynh A.; Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Div Cardiol,Cardiac Magnet Resonance Positron Emi, Boston, MA 02115 USA. [Nagurney, John T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Emergency Med, Boston, MA USA. [Schlett, Christopher L.] Univ Heidelberg Hosp, Dept Diagnost & Intervent Radiol, Heidelberg, Germany. [Zakroysky, Pearl; Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Ctr, Boston, MA USA. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA. [Bamberg, Fabian] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-80539 Munich, Germany. [Wiviott, Stephen D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA. [Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. RP Pursnani, A (reprint author), Harvard Univ, Sch Med, Dept Radiol, Div Cardiol,Cardiac Magnet Resonance Positron Emi, Boston, MA 02115 USA. EM amit.pursnani@gmail.com FU National Institutes of Health/ National Heart Lung Blood Institute (Bethesda, Maryland) [U01HL092040, U01HL092022, 5K24HL113128] FX The study was supported by the grants U01HL092040, U01HL092022 and 5K24HL113128 from National Institutes of Health/ National Heart Lung Blood Institute (Bethesda, Maryland). NR 16 TC 2 Z9 2 U1 2 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 1 PY 2016 VL 117 IS 3 BP 319 EP 324 DI 10.1016/j.amjcard.2015.10.052 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DC4ME UT WOS:000369194200001 PM 26762723 ER PT J AU Gao, L Lee, S Kim, CJ Minami, Y Ong, DS Soeda, T Lowe, H Choi, SY Lerman, A Lee, J Lee, H Uemura, S Yu, B Jang, IK AF Gao, Lei Lee, Stephen Kim, Chong-Jin Minami, Yoshiyasu Ong, Daniel S. Soeda, Tsunenari Lowe, Harry Choi, So-Yeon Lerman, Amir Lee, Jay Lee, Hang Uemura, Shim Yu, Bo Jang, Ik-Kyung TI Incidence and Morphological Predictors of Intrastent Coronary Thrombus After Drug-Eluting Stent Implantation (from a Multicenter Registry) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; BARE-METAL STENTS; SIROLIMUS; MECHANISMS; PATHOLOGY; HUMANS AB The mechanisms responsible for late and very late stent thrombosis remain incompletely understood. This study aimed to evaluate the incidence and morphologic predictors of intrastent thrombus in patients after drug-eluting stent (DES) implantation using optical coherence tomography (OCT). A total of 208 patients with 262 DES who underwent follow-up OCT examination >6 months after DES implantation were included. The detailed vascular morphology including characteristics of neointima was analyzed. Thrombus was identified in 24 patients (11.5%) 11 months after DES implantation. Minimal lumen cross-sectional area was significantly smaller in the thrombus group than in the nonthrombus group (2.9 +/- 1.7 vs 4.6 +/- 2.0 mm(2); p <0.001). No difference was found in the frequency of uncovered or malapposed struts between the 2 groups. Thin-cap fibroatheroma (20.6% vs 0.1%; p <0.001) and heterogeneous neointima (22.2% vs 9.0%; p = 0.001) were more frequently detected in the thrombus group compared to the nonthrombus group. Second-generation DES showed lower incidence of thrombus, uncovered struts, and extrastent lumen compared with first-generation DES. In conclusion, the present OCT study revealed that smaller lumen cross-sectional area and neointimal morphology are important factors associated with intrastent "thrombus. Second-generation DES demonstrated improved arterial healing and a lower incidence of intrastent thrombus compared with first-generation DES. (C) 2016 Elsevier Inc. All rights reserved. C1 [Gao, Lei; Minami, Yoshiyasu; Ong, Daniel S.; Lee, Jay; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Ctr, Boston, MA USA. [Lee, Stephen] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Jang, Ik-Kyung] Kyung Hee Univ, Div Cardiol, Seoul, South Korea. [Soeda, Tsunenari] Nara Med Univ, Dept Med 1, Nara, Japan. [Lowe, Harry] Concord Repatriat Gen Hosp, Dept Cardiol, Sydney, NSW, Australia. [Choi, So-Yeon] Ajou Univ Hosp, Dept Cardiol, Suwon, South Korea. [Lerman, Amir] Mayo Coll Med, Div Cardiovasc Dis, Rochester, MN USA. [Lerman, Amir] Mayo Coll Med, Dept Internal Med, Rochester, MN USA. [Uemura, Shim] Kawasaki Med Univ, Cardiovasc Med Dept, Kurashiki, Okayama, Japan. [Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Key Lab Myocardial Ischemia,Chinese Minist Educ, Harbin, Peoples R China. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.; Jang, IK (reprint author), Kyung Hee Univ, Div Cardiol, Seoul, South Korea.; Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Key Lab Myocardial Ischemia,Chinese Minist Educ, Harbin, Peoples R China. EM yubodr@163.com; IJANG@mgh.harvard.edu FU Boston Scientific Corp.; Medtronic; St. Jude Medical FX Dr. Jang reports receiving a research grant and honorarium from St. Jude Medical and research grant from Boston Scientific Corp. and Medtronic. NR 22 TC 1 Z9 1 U1 2 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 1 PY 2016 VL 117 IS 3 BP 369 EP 375 DI 10.1016/j.amjcard.2015.10.055 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DC4ME UT WOS:000369194200009 PM 26705880 ER PT J AU Akabane, H Sullivan, RJ AF Akabane, Hugo Sullivan, Ryan J. TI The Future of Molecular Analysis in Melanoma: Diagnostics to Direct Molecularly Targeted Therapy SO AMERICAN JOURNAL OF CLINICAL DERMATOLOGY LA English DT Article ID BRAF V600E MUTATION; POLYMERASE-CHAIN-REACTION; BREAST-TUMOR CELLS; METASTATIC MELANOMA; UVEAL MELANOMA; MEK INHIBITION; ACQUIRED-RESISTANCE; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; PERIPHERAL-BLOOD AB Melanoma is a malignancy of pigment-producing cells that is driven by a variety of genetic mutations and aberrations. In most cases, this leads to upregulation of the mitogen-activated protein kinase (MAPK) pathway through activating mutations of upstream mediators of the pathway including BRAF and NRAS. With the advent of effective MAPK pathway inhibitors, including the US FDA-approved BRAF inhibitors vemurafenib and dabrafenib and MEK inhibitor trametinib, molecular analysis has become an integral part of the care of patients with metastatic melanoma. In this article, the key molecular targets and strategies to inhibit these targets therapeutically are presented, and the techniques of identifying these targets, in both tissue and blood, are discussed. C1 [Akabane, Hugo] Metrowest Med Ctr, Dept Med, Framingham, MA USA. [Sullivan, Ryan J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, 55 Fruit St, Boston, MA 02114 USA. RP Sullivan, RJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, 55 Fruit St, Boston, MA 02114 USA. EM rsullivan7@mgh.harvard.edu NR 106 TC 1 Z9 1 U1 0 U2 6 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1175-0561 EI 1179-1888 J9 AM J CLIN DERMATOL JI Am. J. Clin. Dermatol. PD FEB PY 2016 VL 17 IS 1 BP 1 EP 10 DI 10.1007/s40257-015-0159-z PG 10 WC Dermatology SC Dermatology GA DC1PJ UT WOS:000368988100001 PM 26518880 ER PT J AU Shenoy, ES Lee, H Cotter, JA Ware, W Kelbaugh, D Weil, E Walensky, RP Hooper, DC AF Shenoy, Erica S. Lee, Hang Cotter, Jessica A. Ware, Winston Kelbaugh, Douglas Weil, Eric Walensky, Rochelle P. Hooper, David C. TI Impact of rapid screening for discontinuation of methicillin-resistant Staphylococcus aureus contact precautions SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Contact precautions; Costs; Implementation; MRSA ID HEALTH-CARE SETTINGS; XPERT MRSA ASSAY; HOSPITAL DISCHARGE; UNITED-STATES; COLONIZATION; CARRIAGE; DURATION; INFECTIONS; PREVALENCE; DEPRESSION AB Background: A history of methicillin-resistant Staphylococcus aureus (MRSA) is a determinant of inpatient bed assignment. Methods: We assessed outcomes associated with rapid testing and discontinuation of MRSA contact precautions (CP) in a prospective cohort study of polymerase chain reaction (PCR)-based screening in the Emergency Department (ED) of Massachusetts General Hospital. Eligible patients had a history of MRSA and were assessed and enrolled if documented off antibiotics with activity against MRSA and screened for nasal colonization (subject visit). PCR-negative subjects had CP discontinued; the primary outcome was CP discontinuation. We identified semiprivate rooms in which a bed was vacant owing to the CP status of the study subject, calculated the hours of vacancy, and compared idle bed-hours by PCR results. Program costs were compared with predicted revenue. Results: There were 2864 eligible patients, and 648 (22.6%) subject visits were enrolled. Of these, 65.1% (422/648) were PCR-negative and had CP discontinued. PCR-negative subjects had fewer idle bed-hours compared with PCR-positive subjects (28.6 +/- 25.2 vs 75.3 +/- 70.5; P <. 001). The expected revenues from occupied idle beds and averted CP costs ranged from $214,160 to $268,340, and exceeded the program costs. Conclusion: A program of targeted PCR-based screening for clearance of MRSA colonization resulted in expected revenues and decreased CP costs that outweighed programmatic costs. Copyright (c) 2016 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. C1 [Shenoy, Erica S.; Walensky, Rochelle P.; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Shenoy, Erica S.; Walensky, Rochelle P.; Hooper, David C.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Shenoy, Erica S.; Cotter, Jessica A.; Hooper, David C.] Massachusetts Gen Hosp, Infect Control Unit, 55 Fruit St,Bulfinch 334, Boston, MA 02114 USA. [Shenoy, Erica S.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Ware, Winston] Massachusetts Gen Hosp, Clin Care Management Unit, Boston, MA 02114 USA. [Kelbaugh, Douglas] Massachusetts Gen Hosp, Partners Informat Syst, Boston, MA 02114 USA. [Kelbaugh, Douglas; Weil, Eric] Massachusetts Gen Phys Org, Boston, MA USA. [Weil, Eric; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Shenoy, ES; Hooper, DC (reprint author), Massachusetts Gen Hosp, Infect Control Unit, 55 Fruit St,Bulfinch 334, Boston, MA 02114 USA.; Hooper, DC (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM eshenoy@partners.org; dhooper@mgh.harvard.edu FU National Center for Research Resources [KL2 RR025757-03]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center [UL1TR001102]; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health; Harvard University and its affiliated academic healthcare centers; National Institute of Allergy and Infectious Diseases, National Institutes of Health [K01AI110524]; Center for Integration of Medicine and Innovative Technology CIMIT under U.S. Army Medical Research Acquisition Activity CoopsAgreement (CIMIT) [12-1082]; Departmental Funds from the MGH Infection Control Unit FX This work was supported by KL2 RR025757-03 (National Center for Research Resources), UL1TR001102 (Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center; National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health; with financial contributions from Harvard University and its affiliated academic healthcare centers), K01AI110524 (National Institute of Allergy and Infectious Diseases, National Institutes of Health), Center for Integration of Medicine and Innovative Technology CIMIT under U.S. Army Medical Research Acquisition Activity CoopsAgreement (CIMIT No. 12-1082), and Departmental Funds from the MGH Infection Control Unit. The funders did not contribute to the design or conduct of the study; in the collection, management, analysis or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The content of the manuscript is solely the responsibility of the authors and does not necessarily represent the official views of any funders. NR 25 TC 1 Z9 1 U1 2 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD FEB 1 PY 2016 VL 44 IS 2 BP 215 EP 221 DI 10.1016/j.ajic.2015.08.019 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DB8NF UT WOS:000368772700019 PM 26440593 ER PT J AU Al-Maawali, A Barry, BJ Rajab, A El-Quessny, M Seman, A Coury, SN Barkovich, AJ Yang, E Walsh, CA Mochida, GH Stoler, JM AF Al-Maawali, Almundher Barry, Brenda J. Rajab, Anna El-Quessny, Malak Seman, Ann Coury, Stephanie Newton Barkovich, A. James Yang, Edward Walsh, Christopher A. Mochida, Ganeshwaran H. Stoler, Joan M. TI Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE DIAPH1; microcephaly; blindness; seizures; intellectual disability; deafness ID MIGRATION; MUTATION AB Exome sequencing identified homozygous loss-of-function variants in DIAPH1 (c.2769delT; p.F923fs and c.3145C>T; p.R1049X) in four affected individuals from two unrelated consanguineous families. The affected individuals in our report were diagnosed with postnatal microcephaly, early-onset epilepsy, severe vision impairment, and pulmonary symptoms including bronchiectasis and recurrent respiratory infections. A heterozygous DIAPH1 mutation was originally reported in one family with autosomal dominant deafness. Recently, however, a homozygous nonsense DIAPH1 mutation (c.2332C4T; p.Q778X) was reported in five siblings in a single family affected by microcephaly, blindness, early onset seizures, developmental delay, and bronchiectasis. The role of DIAPH1 was supported using parametric linkage analysis, RNA and protein studies in their patients' cell lines and further studies in human neural progenitors cells and a diap1 knockout mouse. In this report, the proband was initially brought to medical attention for profound metopic synostosis. Additional concerns arose when his head circumference did not increase after surgical release at 5 months of age and he was diagnosed with microcephaly and epilepsy at 6 months of age. Clinical exome analysis identified a homozygous DIAPH1 mutation. Another homozygous DIAPH1 mutation was identified in the research exome analysis of a second family with three siblings presenting with a similar phenotype. Importantly, no hearing impairment is reported in the homozygous affected individuals or in the heterozygous carrier parents in any of the families demonstrating the autosomal recessive microcephaly phenotype. These additional families provide further evidence of the likely causal relationship between DIAPH1 mutations and a neurodevelopmental disorder. (c) 2015 Wiley Periodicals, Inc. C1 [Al-Maawali, Almundher; Barry, Brenda J.; El-Quessny, Malak; Seman, Ann; Coury, Stephanie Newton; Walsh, Christopher A.; Mochida, Ganeshwaran H.; Stoler, Joan M.] Boston Childrens Hosp, Div Genet & Genom, Dept Med, 300 Longwood Ave,Hunnewell 536, Boston, MA 02115 USA. [Al-Maawali, Almundher; Barry, Brenda J.; El-Quessny, Malak; Walsh, Christopher A.; Mochida, Ganeshwaran H.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Al-Maawali, Almundher; Barry, Brenda J.; Walsh, Christopher A.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Al-Maawali, Almundher] Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Genet, Muscat, Oman. [Rajab, Anna] Minist Hlth, Directorate Gen Hlth Affairs, Natl Genet Ctr, Muscat, Oman. [Barkovich, A. James] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Yang, Edward] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Yang, Edward] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Walsh, Christopher A.; Mochida, Ganeshwaran H.; Stoler, Joan M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Program Biol & Biomed Sci, Sch Med, Boston, MA USA. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. RP Mochida, GH; Stoler, JM (reprint author), Boston Childrens Hosp, Div Genet & Genom, Dept Med, 300 Longwood Ave,Hunnewell 536, Boston, MA 02115 USA.; Mochida, GH (reprint author), Boston Childrens Hosp, Div Genet & Genom, Dept Med, 300 Longwood Ave,CLS 15070-1,Mail Stop BCH3150, Boston, MA 02115 USA. EM Ganesh.Mochida@childrens.harvard.edu; Joan.Stoler@childrens.harvard.edu FU NINDS [R01 NS 35129] FX Grant sponsor: NINDS; Grant number: R01 NS 35129. NR 7 TC 2 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD FEB PY 2016 VL 170 IS 2 BP 435 EP 440 DI 10.1002/ajmg.a.37422 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA DB9BR UT WOS:000368811500019 PM 26463574 ER PT J AU Hirsch, JA Harvey, HB Barr, RM Donovan, WD Duszak, R Nicola, GN Schaefer, PW Manchikanti, L AF Hirsch, J. A. Harvey, H. B. Barr, R. M. Donovan, W. D. Duszak, R., Jr. Nicola, G. N. Schaefer, P. W. Manchikanti, L. TI Sustainable Growth Rate Repealed, MACRA Revealed: Historical Context and Analysis of Recent Changes in Medicare Physician Payment Methodologies SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID HEALTH-CARE; NEUROINTERVENTIONALISTS; PRIMER C1 [Hirsch, J. A.; Harvey, H. B.; Schaefer, P. W.] Massachusetts Gen Hosp, Dept Radiol, 175 Cambridge St,Suite 200, Boston, MA 02114 USA. [Hirsch, J. A.; Harvey, H. B.; Schaefer, P. W.] Harvard Univ, Sch Med, Boston, MA USA. [Barr, R. M.] Mecklenburg Radiol Associates PA, Charlotte, NC USA. [Donovan, W. D.] Norwich Diagnost Imaging Associates, Norwich, CT USA. [Duszak, R., Jr.] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA. [Duszak, R., Jr.] Harvey L Neiman Hlth Policy Inst, Reston, VA USA. [Nicola, G. N.] Hackensack Univ Med Ctr, Hackensack, NJ USA. [Manchikanti, L.] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, L.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. RP Harvey, HB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 175 Cambridge St,Suite 200, Boston, MA 02114 USA.; Harvey, HB (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM hbharvey@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 20 TC 8 Z9 8 U1 4 U2 7 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 2016 VL 37 IS 2 BP 210 EP 214 DI 10.3174/ajnr.A4522 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DC3HU UT WOS:000369111200010 PM 26585253 ER PT J AU Heit, JJ Pastena, GT Nogueira, RG Yoo, AJ Leslie-Mazwi, TM Hirsch, JA Rabinov, JD AF Heit, J. J. Pastena, G. T. Nogueira, R. G. Yoo, A. J. Leslie-Mazwi, T. M. Hirsch, J. A. Rabinov, J. D. TI Cerebral Angiography for Evaluation of Patients with CT Angiogram-Negative Subarachnoid Hemorrhage: An 11-Year Experience SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID DIGITAL-SUBTRACTION-ANGIOGRAPHY; 3D ROTATIONAL ANGIOGRAPHY; INTRACRANIAL ANEURYSMS; CATHETER ANGIOGRAPHY; COMPUTED-TOMOGRAPHY; REPEAT-ANGIOGRAPHY; INITIAL ANGIOGRAPHY; DIAGNOSTIC YIELD; MANAGEMENT; ETIOLOGY AB BACKGROUND AND PURPOSE: CT angiography is increasingly used to evaluate patients with nontraumatic subarachnoid hemorrhage given its high sensitivity for aneurysms. We investigated the yield of digital subtraction angiography among patients with SAH or intraventricular hemorrhage and a negative CTA. MATERIALS AND METHODS: An 11-year, single-center retrospective review of all consecutive patients with CTA-negative SAH was performed. Noncontrast head CT, CTA, DSA, and MR imaging studies were reviewed by 2 experienced interventional neuroradiologists and 1 neuroradiologist. RESULTS: Two hundred thirty patients (mean age, 54 years; 51% male) with CTA-negative SAH were identified. The pattern of SAH was diffuse (40%), perimesencephalic (31%), sulcal (31%), isolated IVH (6%), or identified by xanthochromia (7%). Initial DSA yield was 13%, including vasculitis/vasculopathy (7%), aneurysm (5%), arteriovenous malformation (0.5%), and dural arteriovenous fistula (0.5%). An additional 6 aneurysms/pseudoaneurysms (4%) were identified by follow-up DSA, and a single cavernous malformation (0.4%) was identified by MRI. No cause of hemorrhage was identified in any patient presenting with isolated intraventricular hemorrhage or xanthochromia. Diffuse SAH was due to aneurysm rupture (17%); perimesencephalic SAH was due to aneurysm rupture (3%) or vasculitis/vasculopathy (1.5%); and sulcal SAH was due to vasculitis/vasculopathy (32%), arteriovenous malformation (3%), or dural arteriovenous fistula (3%). CONCLUSIONS: DSA identifies vascular pathology in 13% of patients with CTA-negative SAH. Aneurysms or pseudoaneurysms are identified in an additional 4% of patients by repeat DSA following an initially negative DSA. All patients with CT-negative SAH should be considered for DSA. The pattern of SAH may suggest the cause of hemorrhage, and aneurysms should specifically be sought with diffuse or perimesencephalic SAH. C1 [Heit, J. J.] Stanford Univ Hosp, Dept Radiol, Intervent Neuroradiol Div, Stanford, CA 94305 USA. [Pastena, G. T.] Albany Med Ctr, Dept Radiol, Albany, NY USA. [Nogueira, R. G.] Emory Univ, Dept Neurol, Sch Med, Marcus Stroke & Neurosci Ctr, Atlanta, GA 30322 USA. [Nogueira, R. G.] Emory Univ, Dept Neurosurg, Sch Med, Marcus Stroke & Neurosci Ctr, Atlanta, GA 30322 USA. [Nogueira, R. G.] Emory Univ, Dept Radiol, Sch Med, Marcus Stroke & Neurosci Ctr, Atlanta, GA 30322 USA. [Leslie-Mazwi, T. M.; Hirsch, J. A.; Rabinov, J. D.] Massachusetts Gen Hosp, Dept Neuroradiol & Intervent Neuroradiol, Boston, MA 02114 USA. [Yoo, A. J.] Texas Stroke Inst, Plano, TX USA. RP Rabinov, JD (reprint author), Massachusetts Gen Hosp, Intervent Neuroradiol, Gray 241,55 Fruit St, Boston, MA 02114 USA. EM jrabinov@partners.org NR 42 TC 3 Z9 3 U1 2 U2 4 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 2016 VL 37 IS 2 BP 297 EP 304 DI 10.3174/ajnr.A4503 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DC3HU UT WOS:000369111200025 PM 26338924 ER PT J AU Murphy, K Oaklander, AL Elias, G Kathuria, S Long, DM AF Murphy, K. Oaklander, A. L. Elias, G. Kathuria, S. Long, D. M. TI Treatment of 213 Patients with Symptomatic Tarlov Cysts by CT-Guided Percutaneous Injection of Fibrin Sealant SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID NERVE-ROOT CYSTS; SACRAL PERINEURIAL CYSTS; TECHNICAL CASE-REPORT; MENINGEAL CYSTS; CLINICAL-SIGNIFICANCE; MICROSURGICAL TREATMENT; CEREBROSPINAL-FLUID; GLUE THERAPY; PATHOGENESIS; SPINE AB This cohort study assesses outcomes in patients who underwent CT-guided aspiration and injection of sacral Tarlov cysts at Johns Hopkins Hospital from 2003-2013. A total of 289 cysts were treated in 213 consecutive patients, with 83% followed for 3-6 years. One year postprocedure, excellent results were obtained in 104 patients (54.2% of patients followed), and good or satisfactory results were obtained in 53 patients (27.6%). BACKGROUND AND PURPOSE: There has been a steady progression of case reports and a small surgical series that report successful surgical treatment of Tarlov cysts with concomitant relief of patients' symptoms and improvement in their neurological dysfunction, yet patients are still told that these lesions are asymptomatic by physicians. The purpose of this study was to analyze the efficacy and safety of intervention in 213 consecutive patients with symptomatic Tarlov cysts treated by CT-guided 2-needle cyst aspiration and fibrin sealing. MATERIALS AND METHODS: This study was designed to assess outcomes in patients who underwent CT-guided aspiration and injection of 1 sacral Tarlov cyst at Johns Hopkins Hospital between 2003 and 2013. In all, 289 cysts were treated in 213 consecutive patients. All these patients were followed for at least 6 months, 90% were followed for 1 year, and 83% were followed for 3-6 years. The aspiration-injection procedure used 2 needles and was performed with the patients under local anesthesia and intravenous anesthesia. In the fibrin-injection stage of the procedure, a commercially available fibrin sealant was injected into the cyst through the deep needle (Tisseel VH). RESULTS: One year postprocedure, excellent results were obtained in 104 patients (54.2% of patients followed), and good or satisfactory results were obtained in 53 patients (27.6%). Thus, 157 patients (81.8%) in all were initially satisfied with the outcome of treatment. At 3-6 years postprocedure, 74.0% of patients followed were satisfied with treatment. There were no clinically significant complications. CONCLUSIONS: The aspiration-injection technique described herein constitutes a safe and efficacious treatment option that holds promise for relieving cyst-related symptoms in many patients with very little risk. C1 [Murphy, K.; Elias, G.] Univ Toronto, Dept Radiol, Toronto, ON M5S 1A1, Canada. [Oaklander, A. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Oaklander, A. L.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol Neuropathol, Sch Med, Boston, MA USA. [Kathuria, S.] Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Long, D. M.] Neurosci Consults, Lutherville Timonium, MD USA. RP Murphy, K (reprint author), Toronto Western Hosp, Dept Radiol, Room 3 Mc 424,399 Bathurst St, Toronto, ON M5T 2S8, Canada. EM Kieran.murphy@uhn.ca FU US Public Health Service (NIH) [K24NS9892] FX This work was supported in part by research grants from the US Public Health Service (NIH K24NS9892). NR 44 TC 3 Z9 3 U1 1 U2 4 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 2016 VL 37 IS 2 BP 373 EP 379 DI 10.3174/ajnr.A4517 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DC3HU UT WOS:000369111200037 PM 26405086 ER PT J AU Serrano-Pozo, A Betensky, RA Frosch, MP Hyman, BT AF Serrano-Pozo, Alberto Betensky, Rebecca A. Frosch, Matthew P. Hyman, Bradley T. TI Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID A-BETA PLAQUES; AMYLOID-BETA; MOUSE MODEL; APOLIPOPROTEIN-E; NEUROFIBRILLARY TANGLES; NATIONAL INSTITUTE; APOE GENOTYPE; NEUROPATHOLOGIC ASSESSMENT; COGNITIVE IMPAIRMENT; NEURITE TRAJECTORIES AB Amyloid (senile) plaques, one of the two pathologic hallmarks of Alzheimer disease (AD), are associated with dystrophic neurites and gial responses, both astrocytic and microglial.;Although plaque burden remains relatively stable through the clinical course of AD, whether these features of local plaque toxicity continue to worsen over the course of the disease is unclear. We performed an unbiased plaque-centered quantification of SMI312(+) dystrophic neurites, GFAP(+) reactive astrocytes, and IBA1(+) and CD68(+) activated microglia in randomly selected dense-core (Thioflavin-S+) plaques from the temporal neocortex of 40 AD subjects with a symptom duration ranging from 4 to 20 years, and nine nondemented control subjects with dense-core plaques. Dystrophic neurites (Kendall tau = 0.34, P = 0.001), reactive astrocytes (Kendall tau = 0.30, P = 0.003), and CD68(+) (Kendall tau = 0.48, P < 0.0001), but not IBA1 microglia (Kendall tau = 0.045, P = 0.655), exhibited a significant positive correlation with symptom duration. When excluding control subjects, only the positive association between CD68+ microglia and symptom duration remained significant (Kendall tau = 0.39, P = 0.0003). The presence of the APOE epsilon 4 allele did not affect these results. We conclude that plaques exert an increasing toxicity in the surrounding neuropil over the clinical course of AD, thereby potentially contributing to cognitive decline. C1 [Serrano-Pozo, Alberto; Betensky, Rebecca A.; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, Massachusetts Alzheimer Dis Res Ctr, Charlestown, MA USA. [Serrano-Pozo, Alberto; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Betensky, Rebecca A.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Serrano-Pozo, Alberto] Univ Iowa Hosp & Clin, Dept Neurol, Iowa City, IA 52242 USA. [Betensky, Rebecca A.] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Hyman, BT (reprint author), Massachusetts Alzheimer Dis Res Ctr, 16th St,Bldg 114, Charlestown, MA 02129 USA. EM bhyman@mgh.harvard.edu OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU NIH grant [P50AG05134]; Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III of the Spanish former Ministerio de Ciencia e Innovacion grant [CM06/00161]; Fundacion Alfonso Martin-Escudero (Madrid, Spain) FX The Massachusetts Alzheimer Disease Research Center is supported by NIH grant P50AG05134 (R.A.B., M.P.F., and B.T.H.). A.S.-P. was supported by nonoverlapping fellowships from the Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III of the Spanish former Ministerio de Ciencia e Innovacion grant CM06/00161 and the Fundacion Alfonso Martin-Escudero (Madrid, Spain). NR 74 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2016 VL 186 IS 2 BP 375 EP 384 DI 10.1016/j.ajpath.2015.10.010 PG 10 WC Pathology SC Pathology GA DC1IL UT WOS:000368969900015 PM 26687817 ER PT J AU Dupre, TV Doll, MA Shah, PP Sharp, CN Kiefer, A Scherzer, MT Saurabh, K Saforo, D Siow, D Casson, L Arteel, GE Jenson, AB Megyesi, J Schnellmann, RG Beverly, LJ Siskind, LJ AF Dupre, Tess V. Doll, Mark A. Shah, Parag P. Sharp, Cierra N. Kiefer, Alex Scherzer, Michael T. Saurabh, Kumar Saforo, Doug Siow, Deanna Casson, Lavona Arteel, Gavin E. Jenson, Alfred Bennett Megyesi, Judit Schnellmann, Rick G. Beverly, Levi J. Siskind, Leah J. TI Suramin protects from cisplatin-induced acute kidney injury SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cisplatin; acute kidney injury; suramin; renoprotective strategies ID ACUTE-RENAL-FAILURE; EPITHELIAL-CELLS; PROXIMAL TUBULE; ER STRESS; NEPHROTOXICITY; RECEPTORS; APOPTOSIS; FIBROSIS; LIVER; MICE AB Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. C1 [Dupre, Tess V.; Doll, Mark A.; Sharp, Cierra N.; Saforo, Doug; Siow, Deanna; Arteel, Gavin E.; Beverly, Levi J.; Siskind, Leah J.] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Shah, Parag P.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Casson, Lavona; Beverly, Levi J.] Univ Louisville, Dept Med, Louisville, KY 40292 USA. [Jenson, Alfred Bennett; Beverly, Levi J.; Siskind, Leah J.] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. [Megyesi, Judit] Univ Arkansas Med Sci, Dept Internal Med, Div Nephrol, Little Rock, AR 72205 USA. [Megyesi, Judit] Cent Arkansas & Vet Healthcare Syst, Little Rock, AR USA. [Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Siskind, LJ (reprint author), Univ Louisville, Dept Pharmacol & Toxicol, James Graham Brown Canc Ctr, 505 S Hancock St,CTRB 204, Louisville, KY 40202 USA. EM leah.siskind@louisville.edu FU National Institutes of Health (NIH) Grant [R01-DK-093462]; NIH [R01-GM-084147, UL1-RR-029882]; Small Business Innovation Research/Small Business Technology Transfer Grant [ES-023767]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs Grant [1BX000851]; South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina FX This work was supported by National Institutes of Health (NIH) Grant R01-DK-093462 (to L. J. Siskind). This work was also supported by NIH Grants R01-GM-084147 (to R. G. Schnellmann), Grant UL1-RR-029882 (to R. G. Schnellmann), and Small Business Innovation Research/Small Business Technology Transfer Grant ES-023767 (to R. G. Schnellmann), Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs Grant 1BX000851 (to R. G. Schnellmann), and the South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina (to R. G. Schnellmann). NR 46 TC 1 Z9 1 U1 2 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB 1 PY 2016 VL 310 IS 3 BP F248 EP F258 DI 10.1152/ajprenal.00433.2015 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA DC2TU UT WOS:000369070400007 PM 26661653 ER PT J AU Navarro-Millan, I Yang, S DuVall, SL Chen, L Baddley, J Cannon, GW Delzell, ES Zhang, J Safford, MM Patkar, NM Mikuls, TR Singh, JA Curtis, JR AF Navarro-Millan, Iris Yang, Shuo DuVall, Scott L. Chen, Lang Baddley, John Cannon, Grant W. Delzell, Elizabeth S. Zhang, Jie Safford, Monika M. Patkar, Nivedita M. Mikuls, Ted R. Singh, Jasvinder A. Curtis, Jeffrey R. TI Association of hyperlipidaemia, inflammation and serological status and coronary heart disease among patients with rheumatoid arthritis: data from the National Veterans Health Administration SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK-FACTORS; C-REACTIVE PROTEIN; FOLLOW-UP; MORTALITY; POLYARTHRITIS; EVENTS; COHORT; VALIDATION; DATABASES AB Objective To examine the association of serum lipids, inflammation and seropositivity on coronary heart disease (CHD) and stroke in patients with rheumatoid arthritis (RA). Methods The incidence of hospitalised myocardial infarction (MI) or stroke was calculated in a cohort of patients with RA receiving care within the national Veterans Health Administration from 1998 to 2011. Cox proportional hazard models were used to examine the association between these outcomes and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as time-varying variables, divided into quintiles. Results There were 37 568 patients with RA in the cohort with mean age of 63 years (SD 12.1); 90% were men. There was a no clear association between LDL-C and CHD/stroke. Compared with lower HDL-C (<34 mg/dL), higher HDL-C (>= 54 mg/dL) was inversely associated with MI (hazard ratio (HR)=0.68, 95% CI 0.55 to 0.85) and stroke (HR=0.69, 95% CI 0.50 to 0.96). Higher CRP >2.17 mg/dL (vs CRP <0.26 mg/dL) was associated with increased risk (HR=2.43, 95% CI 1.77 to 3.33) for MI and 2.02 (95% CI 1.32 to 3.08) for stroke. ESR >47 mm/h compared with <8 mm/h had an HR 1.87 (95% CI 1.39 to 2.52) for MI and 2.00 (95% CI 1.26 to 3.18) for stroke. The association between MI was significant for RA seropositivity (HR=1.23, 95% CI 1.03 to 1.48). Conclusions In this predominantly older male RA cohort, there was no clear association between LDL-C and CHD, whereas higher HDL-C was inversely associated with MI and stroke. CRP and ESR were similarly associated with increase MI risk and stroke, reflecting the prominent role of inflammation in CHD risk in RA. C1 [Navarro-Millan, Iris; Yang, Shuo; Chen, Lang; Baddley, John; Singh, Jasvinder A.; Curtis, Jeffrey R.] Birmingham VA Med Ctr, Birmingham, AL USA. [Navarro-Millan, Iris; Yang, Shuo; Chen, Lang; Baddley, John; Delzell, Elizabeth S.; Zhang, Jie; Safford, Monika M.; Patkar, Nivedita M.; Singh, Jasvinder A.; Curtis, Jeffrey R.] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, 510 20th St S,Fac Off Tower 802D, Birmingham, AL 35294 USA. [DuVall, Scott L.; Cannon, Grant W.] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [DuVall, Scott L.; Cannon, Grant W.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. RP Curtis, JR (reprint author), Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, 510 20th St S,Fac Off Tower 802D, Birmingham, AL 35294 USA. EM jcurtis@uab.edu FU Agency for Healthcare Research and Quality (AHRQ) [R01HS018517]; NIH [AR 053351, R01 AR062376-S1]; Arthritis Foundation [5561] FX This work was supported by the Agency for Healthcare Research and Quality (AHRQ) (R01HS018517). Dr Curtis receives support from the NIH (AR 053351). Dr Navarro-Millan received support from the Arthritis Foundation (5561) and NIH (R01 AR062376-S1). NR 37 TC 6 Z9 7 U1 0 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD FEB PY 2016 VL 75 IS 2 BP 341 EP 347 DI 10.1136/annrheumdis-2013-204987 PG 7 WC Rheumatology SC Rheumatology GA DC1CZ UT WOS:000368955700004 PM 25609412 ER PT J AU Linsenmeyer, K Strymish, J Weir, S Berg, G Brecher, S Gupta, K AF Linsenmeyer, Katherine Strymish, Judith Weir, Susan Berg, Gretchen Brecher, Stephen Gupta, Kalpana TI Activity of Fosfomycin against Extended-Spectrum-beta-Lactamase-Producing Uropathogens in Patients in the Community and Hospitalized Patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; KLEBSIELLA-PNEUMONIAE; INCREASING PREVALENCE; ENTEROBACTERIACEAE; EXPERIENCE; RESISTANCE AB Few oral antibiotics exist for the empirical treatment of extended-spectrum beta-lactamase (ESBL) urinary tract infections (UTI). In this study, we sought to determine the activity of fosfomycin against ESBL-producing uropathogens from patients at 3 Veterans Affairs (VA) facilities between 2010 and 2013. Among the ESBL uropathogens, 19.9% were fosfomycin resistant. Klebsiella species were more likely than Escherichia coli to be resistant (46% versus 4%; P < 0.001). Fosfomycin remains active against a majority of the ESBL uropathogens, although resistance among Klebsiella spp. was higher than that in previous reports. C1 [Linsenmeyer, Katherine; Strymish, Judith; Weir, Susan; Berg, Gretchen; Brecher, Stephen; Gupta, Kalpana] VA Boston Healthcare Syst, West Roxbury, MA USA. [Linsenmeyer, Katherine; Weir, Susan; Berg, Gretchen; Brecher, Stephen; Gupta, Kalpana] Boston Univ, Sch Med, Boston, MA 02118 USA. [Strymish, Judith] Harvard Univ, Sch Med, Boston, MA USA. [Gupta, Kalpana] Natl Ctr Occupat Hlth & Infect Control, Gainesville, FL USA. RP Linsenmeyer, K (reprint author), VA Boston Healthcare Syst, West Roxbury, MA USA.; Linsenmeyer, K (reprint author), Boston Univ, Sch Med, Boston, MA 02118 USA. EM katherine.linsenmeyer@bmc.org NR 18 TC 3 Z9 3 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2016 VL 60 IS 2 BP 1134 EP 1136 DI 10.1128/AAC.02614-15 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DC3ZR UT WOS:000369159800049 PM 26596940 ER PT J AU Silverstein, M Kistin, C Bair-Merritt, M Wiltsey-Stirman, S Feinberg, E Diaz-Linhart, Y Sandler, J Chen, N Cabral, H AF Silverstein, Michael Kistin, Caroline Bair-Merritt, Megan Wiltsey-Stirman, Shannon Feinberg, Emily Diaz-Linhart, Yaminette Sandler, Jenna Chen, Ning Cabral, Howard TI Avoidance as an obstacle to preventing depression among urban women at high risk for violent trauma SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Maternal depression; PTSD; Avoidance; Prevention ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; DOMESTIC VIOLENCE; PTSD SYMPTOMS; MENTAL-HEALTH; PRIMARY-CARE; SELF-REPORT; IMPACT; OUTCOMES; COMORBIDITY AB The impact of depression interventions is often attenuated in women who have experienced trauma. We explored whether psychological avoidance could explain this phenomenon. We synthesized two pilot randomized trials of problem-solving education (PSE) among a total of 93 urban mothers. Outcomes included depressive symptoms and perceived stress. Mothers with avoidant coping styles experienced an average 1.25 episodes of moderately severe depressive symptoms over 3 months of follow-up, compared to 0.40 episodes among those with non-avoidant coping (adjusted incident rate ratio [aIRR] 2.18; 95 % CI 1.06, 4.48). PSE tended to perform better among mothers with non-avoidant coping. Among mothers with non-avoidant coping, PSE mothers experienced an average 0.24 episodes, compared to 0.58 episodes among non-avoidant controls (aIRR 0.27; 95 % CI 0.05, 1.34). Among mothers with avoidant coping, PSE mothers experienced an average 1.26 episodes, compared to 1.20 episodes among avoidant controls (aIRR 0.76; 95 % CI 0.44, 1.33). This trend toward differential impact persisted when avoidance was measured as a problem-solving style and among traumatized mothers with and without avoidant PTSD symptoms. Further research is warranted to explore the hypothesis that psychological avoidance could explain why certain depression treatment and prevention strategies break down in the presence of trauma. C1 [Silverstein, Michael; Kistin, Caroline; Bair-Merritt, Megan; Feinberg, Emily] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Silverstein, Michael; Kistin, Caroline; Bair-Merritt, Megan; Diaz-Linhart, Yaminette; Sandler, Jenna; Chen, Ning] Boston Med Ctr, Dept Pediat, Vose Hall 3,One Boston Med Ctr Pl, Boston, MA 02118 USA. [Wiltsey-Stirman, Shannon] Boston Vet Adm Hosp, Dept Vet Affairs, Natl Ctr PTSD, Boston, MA USA. [Wiltsey-Stirman, Shannon] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02118 USA. [Feinberg, Emily] Boston Univ, Dept Community Hlth Sci, Sch Publ Hlth, Boston, MA 02118 USA. [Cabral, Howard] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA. RP Silverstein, M (reprint author), Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA.; Silverstein, M (reprint author), Boston Med Ctr, Dept Pediat, Vose Hall 3,One Boston Med Ctr Pl, Boston, MA 02118 USA. EM michael.silverstein@bmc.org OI Wiltsey Stirman, Shannon/0000-0001-9917-5078 FU NICHD R03 award [R03HD058075]; NICHD K24 award [K24HD081057] FX This work was funded by an NICHD R03 award (R03HD058075, PI Silverstein); Dr. Silverstein is currently supported in part by an NICHD K24 award (K24HD081057). We thank Barry Zuckerman for his advice in conceptualizing this work. NR 37 TC 0 Z9 0 U1 3 U2 5 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 EI 1435-1102 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD FEB PY 2016 VL 19 IS 1 BP 63 EP 70 DI 10.1007/s00737-015-0521-4 PG 8 WC Psychiatry SC Psychiatry GA DC1XU UT WOS:000369012400009 PM 25833808 ER PT J AU Ward, MM Deodhar, A Akl, EA Lui, A Ermann, J Gensler, LS Smith, JA Borenstein, D Hiratzka, J Weiss, PF Inman, RD Majithia, V Haroon, N Maksymowych, WP Joyce, J Clark, BM Colbert, RA Figgie, MP Hallegua, DS Prete, PE Rosenbaum, JT Stebulis, JA Van Den Bosch, F Yu, DTY Miller, AS Reveille, JD Caplan, L AF Ward, Michael M. Deodhar, Atul Akl, Elie A. Lui, Andrew Ermann, Joerg Gensler, Lianne S. Smith, Judith A. Borenstein, David Hiratzka, Jayme Weiss, Pamela F. Inman, Robert D. Majithia, Vikas Haroon, Nigil Maksymowych, Walter P. Joyce, Janet Clark, Bruce M. Colbert, Robert A. Figgie, Mark P. Hallegua, David S. Prete, Pamela E. Rosenbaum, James T. Stebulis, Judith A. Van Den Bosch, Filip Yu, David T. Y. Miller, Amy S. Reveille, John D. Caplan, Liron TI American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CLASSIFICATION CRITERIA; PSORIATIC-ARTHRITIS; MANAGEMENT; EFFICACY; SAFETY; INJECTIONS; THERAPY; DRUGS; GRADE AB ObjectiveTo provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). MethodsA core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. ResultsIn patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. ConclusionThese recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas. C1 [Ward, Michael M.; Colbert, Robert A.] NIAMSD, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. [Deodhar, Atul; Hiratzka, Jayme; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Akl, Elie A.] Amer Univ Beirut, Beirut, Lebanon. [Akl, Elie A.] McMaster Univ, Hamilton, ON, Canada. [Lui, Andrew; Gensler, Lianne S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ermann, Joerg] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Smith, Judith A.] Univ Wisconsin, Madison, WI 53706 USA. [Borenstein, David] Arthrit & Rheumatism Assoc, Washington, DC USA. [Weiss, Pamela F.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Weiss, Pamela F.] Univ Penn, Philadelphia, PA 19104 USA. [Inman, Robert D.; Haroon, Nigil] Univ Toronto, Toronto, ON, Canada. [Majithia, Vikas] Univ Mississippi, Med Ctr, Jackson, MS USA. [Maksymowych, Walter P.] Univ Alberta, Edmonton, AB, Canada. [Joyce, Janet; Miller, Amy S.] Amer Coll Rheumatol, 60 Execut Pk S,Suite 150, Atlanta, GA 30329 USA. [Clark, Bruce M.] RPT, Vancouver, BC, Canada. [Figgie, Mark P.] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. [Hallegua, David S.] Cedars Sinai Med Ctr, Beverly Hills, CA USA. [Prete, Pamela E.] VA Long Beach Med Ctr, Long Beach, CA USA. [Prete, Pamela E.] Univ Calif Irvine, Irvine, CA USA. [Rosenbaum, James T.] Legacy Devers Eye Inst, Portland, OR USA. [Stebulis, Judith A.] Univ Massachusetts, Worcester, MA 01605 USA. [Van Den Bosch, Filip] Univ Ghent, B-9000 Ghent, Belgium. [Yu, David T. Y.] Univ Calif Los Angeles, Los Angeles, CA USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Caplan, Liron] Denver VA Med Ctr, Denver, CO USA. [Caplan, Liron] Univ Colorado, Aurora, CO USA. RP Ward, MM (reprint author), NIAMSD, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU American College of Rheumatology; Spondylitis Association of America FX This work was supported by the American College of Rheumatology and the Spondylitis Association of America. We thank our patient representative for adding valuable perspectives. We thank Laurie Savage and Charlotte Howard of the Spondylitis Association of America for their partnership on this project. We thank Regina Parker for administrative assistance and Tamara Rader, who with Janet Joyce, developed and reviewed the literature search strategies. We appreciate the contributions of Drs. Robert Hart, Siba Raychaudhuri, and James Witter to the literature review. NR 29 TC 3 Z9 3 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD FEB PY 2016 VL 68 IS 2 BP 151 EP 166 DI 10.1002/acr.22708 PG 16 WC Rheumatology SC Rheumatology GA DB9RT UT WOS:000368855100001 PM 26401907 ER PT J AU Schoenfeld, SR Choi, HK Sayre, EC Avina-Zubieta, JA AF Schoenfeld, Sara R. Choi, Hyon K. Sayre, Eric C. Avina-Zubieta, J. Antonio TI Risk of Pulmonary Embolism and Deep Venous Thrombosis in Systemic Sclerosis: A General Population-Based Study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID RHEUMATOID-ARTHRITIS; ADMINISTRATIVE DATA; VASCULAR-DISEASE; VEIN THROMBOSIS; THROMBOEMBOLISM; SCLERODERMA; EVENTS; INFLAMMATION; INVOLVEMENT; FIBROSIS AB ObjectiveTo determine the risk of venous thromboembolism (VTE) (pulmonary embolism [PE] and deep vein thrombosis [DVT]) in individuals with incident systemic sclerosis (SSc; scleroderma) in the general population. MethodsUsing a population database that includes all residents of British Columbia, Canada, we conducted a cohort study of all patients with incident SSc and up to 10 age-, sex-, and entry time-matched individuals from the general population. We compared incidence rates of PE, DVT, and VTE between the 2 groups according to SSc disease duration. We calculated hazard ratios (HRs), adjusting for confounders. ResultsAmong 1,245 individuals with SSc (83% female, mean age 56 years), the incidence rates of PE, DVT, and VTE were 3.47, 3.48, and 6.56 per 1,000 person-years, respectively, whereas the corresponding rates were 0.78, 0.76, and 1.37 per 1,000 person-years among 12,670 non-SSc individuals. Compared with non-SSc individuals, the multivariable HRs among SSc patients were 3.73 (95% confidence interval [95% CI] 1.98-7.04), 2.96 (95% CI 1.54-5.69), and 3.47 (95% CI 2.14-5.64) for PE, DVT, and VTE, respectively. The age-, sex-, and entry time-matched HRs for PE, DVT, and VTE were highest during the first year after SSc diagnosis (32.77 [95% CI 6.60-162.75], 8.50 [95% CI 3.13-23.04], and 12.03 [95% CI 5.27-27.45], respectively). ConclusionThese findings provide population-based evidence that SSc patients are at a substantially increased risk of VTE, especially within the first year after SSc diagnosis. Increased monitoring for this potentially fatal outcome and its modifiable risk factors is warranted in this patient population. C1 [Schoenfeld, Sara R.; Choi, Hyon K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schoenfeld, Sara R.; Choi, Hyon K.] Harvard Univ, Sch Med, Boston, MA USA. [Choi, Hyon K.; Sayre, Eric C.; Avina-Zubieta, J. Antonio] Arthrit Res Canada, Vancouver, BC, Canada. [Avina-Zubieta, J. Antonio] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Avina-Zubieta, JA (reprint author), 5591 3 Rd, Richmond, BC V6X 2C7, Canada. EM azubieta@arthritisresearch.ca FU Canadian Arthritis Network; Arthritis Society of Canada; British Columbia Lupus Society [10-SRP-IJD-01]; Canadian Institutes for Health Research [MOP 125960, THC 135235] FX Supported by the Canadian Arthritis Network, the Arthritis Society of Canada, the British Columbia Lupus Society (grant 10-SRP-IJD-01), and the Canadian Institutes for Health Research (grants MOP 125960 and THC 135235). NR 51 TC 2 Z9 2 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD FEB PY 2016 VL 68 IS 2 BP 246 EP 253 DI 10.1002/acr.22673 PG 8 WC Rheumatology SC Rheumatology GA DB9RT UT WOS:000368855100011 PM 26212772 ER PT J AU Ward, MM Deodhar, A Akl, EA Lui, A Ermann, J Gensler, LS Smith, JA Borenstein, D Hiratzka, J Weiss, PF Inman, RD Majithia, V Haroon, N Maksymowych, WP Joyce, J Clark, BM Colbert, RA Figgie, MP Hallegua, DS Prete, PE Rosenbaum, JT Stebulis, JA van den Bosch, F Yu, DTY Miller, AS Reveille, JD Caplan, L AF Ward, Michael M. Deodhar, Atul Akl, Elie A. Lui, Andrew Ermann, Joerg Gensler, Lianne S. Smith, Judith A. Borenstein, David Hiratzka, Jayme Weiss, Pamela F. Inman, Robert D. Majithia, Vikas Haroon, Nigil Maksymowych, Walter P. Joyce, Janet Clark, Bruce M. Colbert, Robert A. Figgie, Mark P. Hallegua, David S. Prete, Pamela E. Rosenbaum, James T. Stebulis, Judith A. van den Bosch, Filip Yu, David T. Y. Miller, Amy S. Reveille, John D. Caplan, Liron TI American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CLASSIFICATION CRITERIA; PSORIATIC-ARTHRITIS; MANAGEMENT; EFFICACY; SAFETY; INJECTIONS; THERAPY; DRUGS; GRADE AB Objective. To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). Methods. A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. Results. In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. Conclusion. These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas. C1 [Ward, Michael M.; Colbert, Robert A.] NIAMSD, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. [Deodhar, Atul; Hiratzka, Jayme; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Akl, Elie A.] Amer Univ Beirut, Beirut, Lebanon. [Akl, Elie A.] McMaster Univ, Hamilton, ON, Canada. [Lui, Andrew; Gensler, Lianne S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ermann, Joerg] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Smith, Judith A.] Univ Wisconsin, Madison, WI 53706 USA. [Borenstein, David] Arthrit & Rheumatism Associates, Washington, DC USA. [Weiss, Pamela F.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Weiss, Pamela F.] Univ Penn, Philadelphia, PA 19104 USA. [Inman, Robert D.; Haroon, Nigil] Univ Toronto, Toronto, ON, Canada. [Majithia, Vikas] Univ Mississippi, Med Ctr, Jackson, MS USA. [Maksymowych, Walter P.] Univ Alberta, Edmonton, AB, Canada. [Joyce, Janet; Miller, Amy S.] Amer Coll Rheumatol, 60 Execut Pk S,Suite 150, Atlanta, GA 30329 USA. [Clark, Bruce M.] RPT, Vancouver, BC, Canada. [Figgie, Mark P.] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. [Hallegua, David S.] Cedars Sinai Med Ctr, Beverly Hills, CA USA. [Prete, Pamela E.] VA Long Beach Med Ctr, Long Beach, CA USA. [Prete, Pamela E.] Univ Calif Irvine, Irvine, CA USA. [Rosenbaum, James T.] Legacy Devers Eye Inst, Portland, OR USA. [Stebulis, Judith A.] Univ Massachusetts, Worcester, MA 01605 USA. [van den Bosch, Filip] Univ Ghent, B-9000 Ghent, Belgium. [Yu, David T. Y.] Univ Calif Los Angeles, Los Angeles, CA USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Caplan, Liron] Denver VA Med Ctr, Denver, CO USA. [Caplan, Liron] Univ Colorado, Aurora, CO USA. RP Ward, MM (reprint author), NIAMSD, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH; Abbott; Amgen; Pfizer; Novartis; AbbVie; UCB; Johnson Johnson; Celgene; Iroko; Janssen; Amgen/Pfizer; GlaxoSmithKline; Janssen/Johnson & Johnson/Centocor/Ortho Biotech Products; Janssen Biotech; Augurex; Bristol-Myers Squibb; Medtronic; Ethicon; Q-Med AB; Centocor; IDEC; Xoma; Roche; Isis; Pharmacia; La Jolla Pharma; Genentech; Proctor Gamble; Genelabs; MedImmune; Human Genome Sciences; Array Biopharma; Cipher; Regeneron; Lux Biosciences; Elan; Allergan; Santen; Teva; Sanofi; Janssen/Johnson Johnson FX Drs. Ward and Colbert's work was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH.; Dr. Deodhar has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, Pfizer, and Novartis (less than $10,000 each) and from AbbVie and UCB (more than $10,000 each), and research grants from Novartis, UCB, Johnson & Johnson, and Amgen. Dr. Ermann has received honoraria from AbbVie (less than $10,000) for Advisory Board service. Dr. Gensler has received consulting fees, speaking fees, and/or honoraria from AbbVie, UCB, and Amgen (less than $10,000 each) and research grants from Celgene and AbbVie. Dr. Borenstein has received consulting fees, speaking fees, and/or honoraria from Iroko and Abbott (less than $10,000 each) and honoraria from Clinical Care Options (more than $10,000). Dr. Inman has received consulting fees, speaking fees, and/or honoraria from AbbVie, Abbott, Janssen, Amgen/Pfizer, UCB, Novartis, and Celgene (less than $10,000 each). Dr. Majithia has received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline (less than $10,000). Dr. Haroon has received consulting fees, speaking fees, and/or honoraria from AbbVie, Abbott, Amgen, Janssen/Johnson & Johnson/Centocor/Ortho Biotech Products, Janssen Biotech, Celgene, UCB, and Pfizer (less than $10,000 each). Dr. Maksymowych has received consulting fees, speaking fees, and/or honoraria from AbbVie, UCB, Pfizer, Amgen, Janssen, and Augurex (less than $10,000 each) and receives licensing fees and royalties from Augurex for the 14-3-3 biomarker. Mr. Clark has received consulting fees, speaking fees, and/or honoraria from AbbVie, Abbott, Amgen, Janssen, and Bristol-Myers Squibb (less than $10,000 each). Dr. Figgie has received consulting fees, speaking fees, and/or honoraria from Medtronic and Ethicon (less than $10,000 each). Dr. Hallegua has received consulting fees, speaking fees, and/or honoraria from AbbVie, Q-Med AB, UCB, Bristol-Myers Squibb, Centocor, Amgen, IDEC, Xoma, Novartis, Roche, Isis, Pharmacia, La Jolla Pharma, Genentech, Proctor & Gamble, Genelabs, MedImmune, Human Genome Sciences, Array Biopharma, and Cipher (less than $10,000 each). Dr. Prete has received consulting fees, speaking fees, and/or honoraria from Abbott (less than $10,000). Dr. Rosenbaum has received consulting fees, speaking fees, and/or honoraria from UCB, Regeneron, Xoma, Lux Biosciences, Elan, Allergan, Santen, Teva, Novartis, Sanofi, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, and Genentech (less than $10,000 each) and is a contributor to UpToDate. Dr. van den Bosch has received consulting fees, speaking fees, and/or honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Janssen/Johnson & Johnson, Pfizer, and UCB (less than $10,000 each). Dr. Reveille has received consulting fees, speaking fees, and/or honoraria from Abbott and UCB (less than $10,000 each). NR 29 TC 24 Z9 27 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD FEB PY 2016 VL 68 IS 2 BP 282 EP 298 DI 10.1002/art.39298 PG 17 WC Rheumatology SC Rheumatology GA DC0XY UT WOS:000368942500005 PM 26401991 ER PT J AU Baker, JF Ibrahim, S Billig, E Michaud, K Caplan, L Cannon, GW Stokes, A Majithia, V Mikuls, TR AF Baker, Joshua F. Ibrahim, Said Billig, Erica Michaud, Kaleb Caplan, Liron Cannon, Grant W. Stokes, Andrew Majithia, Vikas Mikuls, Ted R. TI Weight loss, the obesity paradox in rheumatoid arthritis: is it a paradox? Comment on the article by Baker et al Reply SO ARTHRITIS & RHEUMATOLOGY LA English DT Letter ID OLDER-ADULTS C1 [Baker, Joshua F.; Ibrahim, Said] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Baker, Joshua F.; Ibrahim, Said; Billig, Erica] Univ Penn, Philadelphia, PA 19104 USA. [Michaud, Kaleb; Mikuls, Ted R.] Nebraska Western Iowa VA Med Ctr, Omaha, NE USA. [Michaud, Kaleb; Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Caplan, Liron] Denver VA Med Ctr, Denver, CO USA. [Cannon, Grant W.] Salt Lake City VA Med Ctr, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Stokes, Andrew] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Majithia, Vikas] GV Sonny Montgomery VA Med Ctr, Jackson, MS USA. [Majithia, Vikas] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. RP Baker, JF (reprint author), Philadelphia VA Med Ctr, Philadelphia, PA USA. FU CSRD VA [IK2 CX000955] NR 4 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD FEB PY 2016 VL 68 IS 2 BP 553 EP 554 PG 2 WC Rheumatology SC Rheumatology GA DC0XY UT WOS:000368942500035 PM 26555220 ER PT J AU de Velasco, G Bermas, B Choueiri, TK AF de Velasco, Guillermo Bermas, Boonie Choueiri, Toni K. TI Clinical Images: Autoimmune arthropathy and uveitis as complications of programmed death 1 inhibitor treatment SO ARTHRITIS & RHEUMATOLOGY LA English DT Editorial Material ID CELLS; TH17 C1 [de Velasco, Guillermo; Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bermas, Boonie] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP de Velasco, G (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 3 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD FEB PY 2016 VL 68 IS 2 BP 556 EP 556 DI 10.1002/art.39406 PG 1 WC Rheumatology SC Rheumatology GA DC0XY UT WOS:000368942500038 PM 26314277 ER PT J AU Schorderet, P AF Schorderet, Patrick TI NEAT: a framework for building fully automated NGS pipelines and analyses SO BMC BIOINFORMATICS LA English DT Article DE Bioinformatics; Genomics; High throughput sequencing; RNAseq; ChIPseq; NGS pipelines ID INTEGRATIVE GENOMICS VIEWER; SEQUENCING DATA; BROWSER; UCSC; SEQ; VISUALIZATION; DISCOVERY; ALIGNMENT; GALAXY; TOOLS AB Background: The analysis of next generation sequencing (NGS) has become a standard task for many laboratories in the life sciences. Though there exists several tools to support users in the manipulation of such datasets on various levels, few are built on the basis of vertical integration. Here, we present the NExt generation Analysis Toolbox (NEAT) that allows non-expert users including wet-lab scientists to comprehensively build, run and analyze NGS data through double-clickable executables without the need of any programming experience. Results: In comparison to many publicly available tools including Galaxy, NEAT provides three main advantages: (1) Through the development of double-clickable executables, NEAT is efficient (completes within <24 hours), easy to implement and intuitive; (2) Storage space, maximum number of job submissions, wall time and cluster-specific parameters can be customized as NEAT is run on the institution's cluster; (3) NEAT allows users to visualize and summarize NGS data rapidly and efficiently using various built-in exploratory data analysis tools including metagenomic and differentially expressed gene analysis. To simplify the control of the workflow, NEAT projects are built around a unique and centralized file containing sample names, replicates, conditions, antibodies, alignment-, filtering-and peak calling parameters as well as cluster-specific paths and settings. Moreover, the small-sized files produced by NEAT allow users to easily manipulate, consolidate and share datasets from different users and institutions. Conclusions: NEAT provides biologists and bioinformaticians with a robust, efficient and comprehensive tool for the analysis of massive NGS datasets. Frameworks such as NEAT not only allow novice users to overcome the increasing number of technical hurdles due to the complexity of manipulating large datasets, but provide more advance users with tools that ensure high reproducibility standards in the NGS era. NEAT is publically available at https://github.com/pschorderet/NEAT. C1 [Schorderet, Patrick] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Schorderet, Patrick] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Schorderet, P (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Schorderet, P (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM patrick.schorderet@molbio.mgh.harvard.edu FU Advanced Swiss National Foundation Fellowship [P300P3_158516]; National Institute of General Medical Sciences (US) [R37 GM48405-21] FX PS is supported by an Advanced Swiss National Foundation Fellowship (P300P3_158516) and is supported in part through the National Institute of General Medical Sciences (US) grant R37 GM48405-21 awarded to Robert E Kingston. I would like to acknowledge the Kingston Lab members for stimulating discussions, feedback and testing; particularly Alan Rodrigues, Sharon Marr, Aaron Plys, Ozlem Yildirim, Ruslan Sadreyev and Bob Kingston for critical reading during the preparation of the manuscript. NR 27 TC 0 Z9 0 U1 2 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD FEB 1 PY 2016 VL 17 AR 53 DI 10.1186/s12859-016-0902-3 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA DC2MK UT WOS:000369050600001 PM 26830846 ER PT J AU Saeed, H Mantagos, IS Chodosh, J AF Saeed, Hajirah Mantagos, Iason S. Chodosh, James TI Complications of Stevens-Johnson syndrome beyond the eye and skin SO BURNS LA English DT Review DE Stevens-Johnson syndrome; Toxic epidermal necrolysis ID TOXIC EPIDERMAL NECROLYSIS; AMNIOTIC MEMBRANE TRANSPLANTATION; OF-THE-LITERATURE; BRONCHIOLITIS OBLITERANS; ERYTHEMA MULTIFORME; ESOPHAGEAL STRICTURE; PULMONARY COMPLICATIONS; VAGINAL STENOSIS; LYELL SYNDROME; BILE-DUCTS AB Introduction: Ocular and cutaneous disease are common chronic sequelae of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and have been well described in the literature. Long-term complications affecting other organ systems have not been so well described. The purpose of this review article is to highlight non-ocular and non-cutaneous chronic complications of SJS/TEN. Methods: The PubMed database was searched for the keywords "Stevens-Johnson syndrome'' and "toxic epidermal necrolysis'' through September 1, 2014. Relevant articles were then reviewed in full. Results: 138 articles in the English language were found that described chronic sequelae of SJS/TEN. Our search revealed six affected organ systems other than the eyes and integument, with chronic sequelae from SJS/TEN: respiratory, gastrointestinal/hepatic, oral, otorhinolaryngologic, gynecologic/genitourinary, and renal. Complications involving these organs systems appeared likely to reduce the quality of life for SJS/TEN survivors. Discussion: SJS/TEN is a multi-organ disease requiring multidisciplinary care from a variety of specialists. Affected patients have complex hospital stays, and their quality of life may be severely impacted by multiple long-term complications. We believe that preventative care in the acute setting might limit the development and progression of many of the sequelae described above. (C) 2015 Elsevier Ltd and ISBI. All rights reserved. C1 [Saeed, Hajirah; Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. [Mantagos, Iason S.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA. RP Chodosh, J (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Hajirah_Saeed@meei.harvard.edu; Jason.Mantagos@childrens.harvard.edu; James_Chodosh@meei.harvard.edu OI Mantagos, Iason/0000-0002-3510-5465 FU Research to Prevent Blindness, New York, NY FX This work was supported in part by an unrestricted grant to the Department of Ophthalmology, Harvard Medical School, by Research to Prevent Blindness, New York, NY. We would like to acknowledge Louise Collins of the Howe Library at Massachusetts Eye and Ear Infirmary for her help in searching for and obtaining articles of interest. NR 102 TC 2 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 EI 1879-1409 J9 BURNS JI Burns PD FEB PY 2016 VL 42 IS 1 BP 20 EP 27 DI 10.1016/j.burns.2015.03.012 PG 8 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA DB9MP UT WOS:000368840600004 PM 25865527 ER PT J AU Sircar, M Bhatia, A Munshi, M AF Sircar, Mousumi Bhatia, Ashmeet Munshi, Medha TI Review of Hypoglycemia in the Older Adult: Clinical Implications and Management SO CANADIAN JOURNAL OF DIABETES LA English DT Review DE diabetes; geriatric; hypoglycemia; older adult; patient safety ID TYPE-2 DIABETES-MELLITUS; ELDERLY-PATIENTS; COGNITIVE IMPAIRMENT; GLYCEMIC CONTROL; GLUCOSE CONTROL; WORKING PARTY; PEOPLE EDWPOP; RISK; INSULIN; SULFONYLUREAS AB The aging of the population is a worldwide phenomenon. The prevalence of diabetes rises with increasing age, so the personal and financial costs of diabetes in the aging population have become significant burdens. In 2012, 104 billion (59%) of the estimated $176 billion in United States healthcare expenditures attributable to diabetes were utilized by patients older than 65 years of age [American Diabetes Association (1)]. With improvement in diabetes management and better glycemic control in the general population, there is an increase in the prevalence of hypoglycemia, which is the complication of the treatment of diabetes. Older adults with diabetes have a higher risk for hypoglycemia due to altered adaptive physiologic responses to low glucose levels. These patients also have comorbidities, such as cognitive and functional loss, that interfere with prompt identification and/or appropriate treatment of hypoglycemia. Older adults who suffer from hypoglycemia also have increased risk for falls, fall-related fractures, seizures and comas and exacerbation of chronic conditions, such as cognitive dysfunction and cardiac events. Thus, hypoglycemia in the older adult must be proactively avoided to decrease significant morbidity and mortality. Education of the patients and caregivers is important in prevention and treatment of hypoglycemia. In this article, we discuss the important aspects and unique challenges pertaining to hypoglycemia in older population. We also highlight the risks, consequences and prevention and management strategies for hypoglycemia that can be used by healthcare providers caring for older populations. (C) 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved. C1 [Sircar, Mousumi; Bhatia, Ashmeet; Munshi, Medha] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Munshi, Medha] Joslin Diabet Ctr, Boston, MA 02215 USA. [Sircar, Mousumi; Bhatia, Ashmeet; Munshi, Medha] Harvard Univ, Sch Med, Boston, MA USA. RP Munshi, M (reprint author), 110 Francis St,LMOB 1B, Boston, MA 02215 USA. EM mmunshi@bidmc.harvard.edu NR 46 TC 1 Z9 1 U1 4 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1499-2671 J9 CAN J DIABETES JI Can. J. Diabetes PD FEB PY 2016 VL 40 IS 1 BP 66 EP 72 DI 10.1016/j.jcjd.2015.10.004 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DC4DQ UT WOS:000369170800013 PM 26752195 ER PT J AU Santiago-Walker, A Gagnon, R Mazumdar, J Casey, M Long, GV Schadendorf, D Flaherty, K Kefford, R Hauschild, A Hwu, P Haney, P O'Hagan, A Carver, J Goodman, V Legos, J Martin, AM AF Santiago-Walker, Ademi Gagnon, Robert Mazumdar, Jolly Casey, Michelle Long, Georgina V. Schadendorf, Dirk Flaherty, Keith Kefford, Richard Hauschild, Axel Hwu, Patrick Haney, Patricia O'Hagan, Anne Carver, Jennifer Goodman, Vicki Legos, Jeffrey Martin, Anne-Marie TI Correlation of BRAF Mutation Status in Circulating-Free DNA and Tumor and Association with Clinical Outcome across Four BRAFi and MEKi Clinical Trials SO CLINICAL CANCER RESEARCH LA English DT Article ID DOSE-ESCALATION TRIAL; METASTATIC MELANOMA; NUCLEIC-ACIDS; OPEN-LABEL; PHASE-II; CANCER; DABRAFENIB; PLASMA; SERUM; MULTICENTER AB Purpose: Tumor-derived circulating cell-free DNA (cfDNA) is a potential alternative source from which to derive tumor mutation status. cfDNA data from four clinical studies of the BRAF inhibitor (BRAFi) dabrafenib or the MEK inhibitor (MEKi) trametinib were analyzed to determine the association between BRAF mutation status in cfDNA and tumor tissue, and the association of BRAF cfDNA mutation status with baseline factors and clinical outcome. Experimental Design: Patients with BRAF V600 mutation-positive melanoma were enrolled in each study after central confirmation of BRAF status in tumor using a PCR-based assay. BRAF mutation status in cfDNA from patient plasma collected at baseline, 732 of 836 (88%) enrolled patients in total, was determined. Results: BRAF mutations were detectable in cfDNA in 76% and 81% of patients with BRAF V600E/V600K-positive tumors, respectively. Patients negative for BRAF mutations in cfDNA had longer progression-free survival (PFS) and overall survival in each of the four studies, compared with patients with detectable cfDNA BRAF mutations. The presence of BRAF-mutant cfDNA was an independent prognostic factor for PFS after multivariate adjustment for baseline factors in three of four studies. Patients negative for BRAF mutation-positive cfDNA in plasma had higher response rates to dabrafenib and trametinib. Conclusions: BRAF mutations in cfDNA are detectable in >75% of late-stage melanoma patients with BRAF mutation-positive tumors. The lack of circulating, BRAF mutation-positive cfDNA is clinically significant for metastatic melanoma patients, and may be a prognostic marker for better disease outcome. (C) 2015 AACR. C1 [Santiago-Walker, Ademi; Gagnon, Robert; Mazumdar, Jolly; Casey, Michelle; Haney, Patricia; O'Hagan, Anne; Carver, Jennifer; Goodman, Vicki; Legos, Jeffrey; Martin, Anne-Marie] GlaxoSmithKline, Collegeville, PA 19426 USA. [Long, Georgina V.; Kefford, Richard] Melanoma Inst Australia, Dept Med Oncol, Sydney, NSW, Australia. [Long, Georgina V.; Kefford, Richard] Univ Sydney, Sydney, NSW, Australia. [Schadendorf, Dirk] Univ Hosp Essen, Dept Dermatol, Essen, Germany. [Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Kefford, Richard] Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia. [Hauschild, Axel] Univ Hosp Schleswig Holstein, Dept Dermatol, Holstein, Germany. [Hwu, Patrick] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Santiago-Walker, Ademi; O'Hagan, Anne] Janssen, 1400 McKean Rd, Spring House, PA USA. [Gagnon, Robert; Carver, Jennifer; Legos, Jeffrey] Novartis Pharmaceut, 1 Hlth Plaza, E Hanover, NJ USA. [Casey, Michelle; Haney, Patricia] Pfizer, 500 Arcola Rd, Collegeville, PA USA. [Goodman, Vicki] Bristol Myers Squibb, 3551 Lawrenceville Princeton, Lawrence Township, NJ USA. [Martin, Anne-Marie] Adaptimmune LLC, Univ City Sci Ctr, 3711 Market St,8th Floor, Philadelphia, PA USA. RP Gagnon, R (reprint author), Novartis Pharmaceut, 151 S Warner Rd, Collegeville, PA 19426 USA. EM Robert.Gagnon@novartis.com FU GlaxoSmithKline [NCT01153763, NCT01227889, NCT01266967, NCT01245062] FX This study (NCT01153763, NCT01227889, NCT01266967, and NCT01245062) was funded by GlaxoSmithKline. NR 30 TC 11 Z9 12 U1 1 U2 8 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 FEB 1 PY 2016 VL 22 IS 3 BP 567 EP 574 DI 10.1158/1078-0432.CCR-15-0321 PG 8 WC Oncology SC Oncology GA DC2XY UT WOS:000369083300008 PM 26446943 ER PT J AU Huang, RY Rahman, R Ballman, KV Felten, SJ Anderson, SK Ellingson, BM Nayak, L Lee, EQ Abrey, LE Galanis, E Reardon, DA Pope, WB Cloughesy, TF Wen, PY AF Huang, Raymond Y. Rahman, Rifaquat Ballman, Karla V. Felten, Sara J. Anderson, S. Keith Ellingson, Benjamin M. Nayak, Lakshmi Lee, Eudocia Q. Abrey, Lauren E. Galanis, Evanthia Reardon, David A. Pope, Whitney B. Cloughesy, Timothy F. Wen, Patrick Y. TI The Impact of T2/FLAIR Evaluation per RANO Criteria on Response Assessment of Recurrent Glioblastoma Patients Treated with Bevacizumab SO CLINICAL CANCER RESEARCH LA English DT Article ID PROGRESSION-FREE SURVIVAL; HIGH-GRADE GLIOMAS; PHASE-II TRIAL; END-POINT; ANTIANGIOGENIC THERAPY; MALIGNANT GLIOMA; PLUS IRINOTECAN; TEMOZOLOMIDE; MULTIFORME AB Purpose: The RANO criteria have not been assessed using outcome data from prospective trials. We examined the radiologic data of patients with recurrent glioblastoma from the randomized phase II trial (AVF3708g) to determine the effect of including T2/FLAIR evaluation as per RANO criteria on measurements of objective response rates (ORRs) and progression-free survival (PFS) compared with assessment based on contrast enhancement (Macdonald criteria). Experimental Design: The ORRs and median PFS were determined using the RANO criteria and compared with those obtained using the Macdonald criteria. Landmark analyses were performed at 2, 4, and 6 months, and Cox proportional hazard models were used to determine the associations between OR and progression with subsequent survival. Results: The ORRs were 0.331 [95% confidence interval (CI), 0.260-0.409] and 0.393 (95% CI, 0.317-0.472) by RANO and Macdonald criteria, respectively (P < 0.0001). The median PFS was 4.6 months (95% CI, 4.1-5.5) using RANO criteria, compared with 6.4 months ( 95% CI, 5.5-7.1) as determined by Macdonald criteria (P = 0.01). At 2-, 4-, and 6-month landmarks, both OR status and PFS determined by either RANO or Macdonald criteria were predictive of overall survival [OS; hazard ratios for 4- month landmark (ORHR = 1.93, P = 0.0012; PFS HR, 4.23, P < 0.0001)]. Conclusions: The inclusion of T2/FLAIR assessment resulted in statistically significant differences in median PFS and ORRs compared with assessment of solely enhancing tumor (Macdonald criteria), although OR and PFS determined by both RANO and Macdonald criteria correlated with OS. (C) 2015 AACR. C1 [Huang, Raymond Y.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Huang, Raymond Y.; Rahman, Rifaquat; Nayak, Lakshmi; Lee, Eudocia Q.; Reardon, David A.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Ballman, Karla V.; Felten, Sara J.; Anderson, S. Keith; Pope, Whitney B.] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Abrey, Lauren E.] F Hoffmann Roche Ltd, Div Pharmaceut, Prod Dev Oncol, Basel, Switzerland. [Galanis, Evanthia] Mayo Clin, Dept Oncol, Div Med Oncol, Rochester, MN USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Huang, RY (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM ryhuang@partners.org FU ARRS/ASNR scholar award FX Dr. R.Y. Huang was supported by ARRS/ASNR scholar award (foundation grant). NR 24 TC 3 Z9 3 U1 0 U2 5 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 FEB 1 PY 2016 VL 22 IS 3 BP 575 EP 581 DI 10.1158/1078-0432.CCR-14-3040 PG 7 WC Oncology SC Oncology GA DC2XY UT WOS:000369083300009 PM 26490307 ER PT J AU Lu, DH Sinnott, JA Valdimarsdottir, U Fang, F Gerke, T Tyekucheva, S Fiorentino, M Lambe, M Sesso, HD Sweeney, CJ Wilson, KM Giovannucci, EL Loda, M Mucci, LA Fall, K AF Lu, Donghao Sinnott, Jennifer A. Valdimarsdottir, Unnur Fang, Fang Gerke, Travis Tyekucheva, Svitlana Fiorentino, Michelangelo Lambe, Mats Sesso, Howard D. Sweeney, Christopher J. Wilson, Kathryn M. Giovannucci, Edward L. Loda, Massimo Mucci, Lorelei A. Fall, Katja TI Stress-Related Signaling Pathways in Lethal and Nonlethal Prostate Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID BETA-BLOCKERS; EXPRESSION; RECEPTOR; SURVIVAL; GROWTH; CELLS; MEN; ASSOCIATION; PROGRESSION; MECHANISMS AB Purpose: Recent data suggest that neuroendocrine signaling may influence progression in some cancers. We aimed to determine whether genes within the five major stress-related signaling pathways are differentially expressed in tumor tissue when comparing prostate cancer patients with lethal and non-lethal disease. Experimental Design: We measured mRNA expression of 51 selected genes involved in predetermined stress-related signaling pathways (adrenergic, glucocorticoid, dopaminergic, serotoninergic, and muscarinic systems) in tumor tissue and normal prostate tissue collected from prostate cancer patients in the Physicians' Health Study (n = 150; n = 82 with normal) and the Health Professionals Follow-Up Study (n = 254; n = 120 with normal). We assessed differences in pathway expression in relation to prostate cancer lethality as the primary outcome and to biomarkers as secondary outcomes. Results: Differential mRNA expression of genes within the adrenergic (P = 0.001), glucocorticoid (P < 0.0001), serotoninergic (P = 0.0019), and muscarinic (P = 0.0045) pathways in tumor tissue was associated with the risk of lethality. The adrenergic pathway was also statistically significant (P = 0.001) when comparing against differential expression of genes not involved in the pathways. In adjacent normal prostate tissue, none of the pathways was clearly differentially expressed between lethal and nonlethal prostate cancer. The glucocorticoid and adrenergic pathways were associated with cell proliferation, while the glucocorticoid pathway was additionally associated with angiogenesis and perineural invasion. Conclusions: Our study suggests that stress-related signaling pathways, particularly the adrenergic and glucocorticoid, may be dysregulated in the tumors of men whose prostate cancer proves to be lethal, and motivates further investigation of these pathways in functional studies. (C)2015 AACR. C1 [Lu, Donghao; Valdimarsdottir, Unnur; Fang, Fang; Lambe, Mats] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Sinnott, Jennifer A.] Ohio State Univ, Dept Stat, 1958 Neil Ave, Columbus, OH 43210 USA. [Sinnott, Jennifer A.; Valdimarsdottir, Unnur; Gerke, Travis; Fiorentino, Michelangelo; Sesso, Howard D.; Wilson, Kathryn M.; Giovannucci, Edward L.; Mucci, Lorelei A.; Fall, Katja] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Valdimarsdottir, Unnur; Wilson, Kathryn M.] Univ Iceland, Sch Hlth Sci, Ctr Publ Hlth Sci, Fac Med, Reykjavik, Iceland. [Gerke, Travis] Univ Florida, Coll Med, Dept Epidemiol, Gainesville, FL USA. [Gerke, Travis] Univ Florida, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA. [Tyekucheva, Svitlana] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Fiorentino, Michelangelo; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Addarii Inst, Pathol Unit, Bologna, Italy. [Lambe, Mats] Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Sesso, Howard D.; Giovannucci, Edward L.; Loda, Massimo; Mucci, Lorelei A.] Harvard Univ, Sch Med, Boston, MA USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA. [Sweeney, Christopher J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Mucci, Lorelei A.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Fall, Katja] Univ Orebro, Clin Epidemiol & Biostat, Fac Med & Hlth, SE-70182 Orebro, Sweden. RP Sinnott, JA (reprint author), Ohio State Univ, Dept Stat, 1958 Neil Ave, Columbus, OH 43210 USA.; Lu, DH (reprint author), Karolinska Inst, Nobels Vag 12A,Box 281, S-17177 Stockholm, Sweden. EM DONGHAO.LU@KI.SE; jsinnott@stat.osu.edu FU Partial Financing of New Doctoral Student (KID) from the Karolinska Institutet; NIH [T32GM074897, T32 CA09001, CA136578, CA090381]; A. David Mazzone Career Development Award; Svenska Sallskapet for Medicinsk Forskning; Cancerfonden [CAN 2013/650]; Strategic funding from Orebro University; Prostate Cancer Foundation; [CA34944]; [CA40360]; [CA097193]; [HL26490]; [HL34595]; [CA133891]; [CA141298]; [P01CA055075] FX The Physicians' Health Study was supported by grants CA34944, CA40360, CA097193, HL26490, and HL34595. The Health Professionals Follow-up Study was supported by grants CA133891, CA141298, and P01CA055075. This work was supported by Partial Financing of New Doctoral Student (KID) from the Karolinska Institutet (to D. Lu); by the NIH grants T32GM074897, T32 CA09001 (to J.A. Sinnott), CA136578 and CA090381 (to L.A. Mucci); by the A. David Mazzone Career Development Award (JAS); by Svenska Sallskapet for Medicinsk Forskning (to F. Fang); by Cancerfonden (CAN 2013/650) and Strategic funding from Orebro University (to K. Fall), and the Prostate Cancer Foundation (to L.A. Mucci). NR 38 TC 0 Z9 0 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 FEB 1 PY 2016 VL 22 IS 3 BP 765 EP 772 DI 10.1158/1078-0432.CCR-15-0101 PG 8 WC Oncology SC Oncology GA DC2XY UT WOS:000369083300026 PM 26490316 ER PT J AU Christensen, KD Vassy, JL Jamal, L Lehmann, LS Slashinski, MJ Perry, DL Robinson, JO Blumenthal-Barby, J Feuerman, LZ Murray, MF Green, RC McGuire, AL AF Christensen, K. D. Vassy, J. L. Jamal, L. Lehmann, L. S. Slashinski, M. J. Perry, D. L. Robinson, J. O. Blumenthal-Barby, J. Feuerman, L. Z. Murray, M. F. Green, R. C. McGuire, A. L. CA MedSeq Project Team TI Are physicians prepared for whole genome sequencing? a qualitative analysis SO CLINICAL GENETICS LA English DT Article DE genetic literacy; physicians; preparedness; qualitative research; self-efficacy; whole genome sequencing ID GENETICS SERVICES; MEDSEQ PROJECT; CLINICAL CARE; MEDICINE; PERSPECTIVES; INTEGRATION; EDUCATION; DELIVERY; OUTCOMES; SOCIETY AB Although the integration of whole genome sequencing (WGS) into standard medical practice is rapidly becoming feasible, physicians may be unprepared to use it. Primary care physicians (PCPs) and cardiologists enrolled in a randomized clinical trial of WGS received genomics education before completing semi-structured interviews. Themes about preparedness were identified in transcripts through team-based consensus-coding. Data from 11 PCPs and 9 cardiologists suggested that physicians enrolled in the trial primarily to prepare themselves for widespread use of WGS in the future. PCPs were concerned about their general genomic knowledge, while cardiologists were concerned about how to interpret specific types of results and secondary findings. Both cohorts anticipated preparing extensively before disclosing results to patients by using educational resources with which they were already familiar, and both cohorts anticipated making referrals to genetics specialists as needed. A lack of laboratory guidance, time pressures, and a lack of standards contributed to feeling unprepared. Physicians had specialty-specific concerns about their preparedness to use WGS. Findings identify specific policy changes that could help physicians feel more prepared, and highlight how providers of all types will need to become familiar with interpreting WGS results. C1 [Christensen, K. D.; Vassy, J. L.; Lehmann, L. S.; Perry, D. L.; Green, R. C.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Christensen, K. D.; Vassy, J. L.; Lehmann, L. S.; Perry, D. L.; Green, R. C.] Harvard Univ, Sch Med, EC Alumnae Bldg,Suite 301,41 Ave Louis Pasteur, Boston, MA 02115 USA. [Vassy, J. L.] VA Boston Healthcare Syst, Sect Gen Internal Med, Boston, MA USA. [Jamal, L.; Robinson, J. O.; Blumenthal-Barby, J.; Feuerman, L. Z.; McGuire, A. L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Slashinski, M. J.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Murray, M. F.] Geisinger Hlth Syst, Genom Med Inst, Danville, PA USA. [Green, R. C.] Brigham & Womens Hosp, Partners Personalized Med, 75 Francis St, Boston, MA 02115 USA. RP Christensen, KD (reprint author), Harvard Univ, Sch Med, EC Alumnae Bldg,Suite 301,41 Ave Louis Pasteur, Boston, MA 02115 USA.; Christensen, KD (reprint author), Brigham & Womens Hosp, EC Alumnae Bldg,Suite 301,41 Ave Louis Pasteur, Boston, MA 02115 USA. EM kchristensen@genetics.med.harvard.edu FU NHGRI [U01HG006500]; National Institutes of Health (NIH) [U19HD077671, F32HG006993, KL2TR001100] FX This study is a Clinical Sequencing Exploratory Research (CSER) program project supported by NHGRI U01HG006500. This work was also supported by the National Institutes of Health (NIH) grants U19HD077671, F32HG006993, and KL2TR001100). The authors thank the members and participants of the MedSeq Project for their important contributions. The authors thank 5AM Solutions, Inc. (Rockville, MD) for their help in customizing the workflow of the 'My Family Health Portrait' web tool for this study. NR 43 TC 8 Z9 8 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9163 EI 1399-0004 J9 CLIN GENET JI Clin. Genet. PD FEB PY 2016 VL 89 IS 2 BP 228 EP 234 DI 10.1111/cge.12626 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA DB8ZY UT WOS:000368806900014 PM 26080898 ER PT J AU Heyne, TF Robinban, NH Lin, AE AF Heyne, T. F. Robinban, N. H. Lin, A. E. TI Sixteenth-century German woodcut of a male infant with possible disorganization SO CLINICAL GENETICS LA English DT Editorial Material DE art; congenital; disorganization; German; history; malformation; woodcut ID MOUSE MUTANT DISORGANIZATION; POSSIBLE HUMAN HOMOLOG; HUMANS; MICE AB History has preserved a beautiful 16th century woodcut print, which depicts an infant with several malformations. The German inscription describes the infant's hypotonia and ectopic growths, and the image itself shows a child with an ectopic accessory third lower limb, a large papilla, and an omphalocele-like growth. The case' bears striking similarity to reported human cases of the disorganization (Ds) syndrome. This article describes the woodcut, describes Ds, and then explains how the image may represent the earliest depiction of Ds in history. C1 [Heyne, T. F.] Massachusetts Gen Hosp, Harvard Internal Med & Pediat Residency Program, Boston, MA 02114 USA. [Robinban, N. H.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Robinban, N. H.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Robinban, N. H.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Lin, A. E.] Mass Gen Hosp Children, Med Genet Unit, Boston, MA USA. RP Heyne, TF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Internal Med & Pediat, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM theyne@partners.org NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9163 EI 1399-0004 J9 CLIN GENET JI Clin. Genet. PD FEB PY 2016 VL 89 IS 2 BP 269 EP 271 DI 10.1111/cge.12643 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA DB8ZY UT WOS:000368806900020 PM 26183129 ER PT J AU Hashoul-Andary, R Assayag-Nitzan, Y Yuval, K Aderka, IM Litz, B Bernstein, A AF Hashoul-Andary, Raneen Assayag-Nitzan, Yaara Yuval, Kim Aderka, Idan M. Litz, Brett Bernstein, Amit TI A Longitudinal Study of Emotional Distress Intolerance and Psychopathology Following Exposure to a Potentially Traumatic Event in a Community Sample SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Anxiety Sensitivity; Distress Tolerance; Trauma; PTSD; Psychopathology; Structural Equation Modeling ID POSTTRAUMATIC-STRESS-DISORDER; PTSD SYMPTOM SEVERITY; NATIONAL COMORBIDITY SURVEY; SELF-REPORT MEASURE; ANXIETY SENSITIVITY; PANIC DISORDER; INTEROCEPTIVE EXPOSURE; PSYCHIATRIC-DISORDERS; INCREMENTAL VALIDITY; STRUCTURAL MODELS AB This study focused on better understanding the association between anxiety sensitivity (AS), distress tolerance (DT), and psychopathology, including posttraumatic stress, depression, panic and suicidality, in the aftermath of a potentially traumatizing event. A community-based sample of 151 adults exposed to the Mount Carmel Forest Fire Disaster were assessed within 30-days of exposure (T1) and then at 3- (T2) and 6-month (T3) follow-up intervals. At T1, AS, DT, and psychopathology symptoms loaded on a single common latent factor reflecting Emotional Avoidance and Distress; whereas by T2 AS-DT and psychopathology symptoms diverged into distinct latent variables-Emotional Distress Intolerance and Distress Post-Trauma, respectively. Levels of Emotional Distress and Avoidance at T1 predicted levels of Emotional Distress Intolerance as well as Distress Post-Trauma at T2. Finally, levels of Emotional Intolerance at T2 predicted levels of Distress Post-Trauma at T3 above and beyond the strong stability effects of Distress Post-Trauma over time. Findings are discussed with respect to their theoretical and clinical implications for understanding and promoting resilience to, and recovery following, exposure to potentially traumatic events. C1 [Hashoul-Andary, Raneen; Assayag-Nitzan, Yaara; Yuval, Kim; Aderka, Idan M.; Bernstein, Amit] Univ Haifa, Dept Psychol, IL-31905 Haifa, Israel. [Litz, Brett] VA Boston Healthcare Syst, Boston, MA USA. [Litz, Brett] Boston Univ, Boston, MA 02215 USA. RP Bernstein, A (reprint author), Univ Haifa, Dept Psychol, IL-31905 Haifa, Israel. EM abernstein@psy.haifa.ac.il FU Israeli Science Foundation (ISF); Israeli Council for Higher Education Yigal Alon Fellowship; European Union FP-7 Marie Curie Fellowship International Reintegration Grant; Psychology Beyond Borders Mission Award; Rothschild-Caesarea Foundation FX Dr. Bernstein recognizes the funding support from the Israeli Science Foundation (ISF), Israeli Council for Higher Education Yigal Alon Fellowship, the European Union FP-7 Marie Curie Fellowship International Reintegration Grant, Psychology Beyond Borders Mission Award, and the Rothschild-Caesarea Foundation. We thank Dr. Barbara M. Byrne for her kind assistance with the SEM analyses in AMOS. NR 100 TC 0 Z9 0 U1 5 U2 16 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD FEB PY 2016 VL 40 IS 1 BP 1 EP 13 DI 10.1007/s10608-015-9730-4 PG 13 WC Psychology, Clinical SC Psychology GA DC1VP UT WOS:000369006100001 ER PT J AU Riddle, MA Maher, BS Wang, Y Grados, M Bienvenu, OJ Goes, FS Cullen, B Murphy, DL Rauch, SL Greenberg, BD Knowles, JA McCracken, JT Pinto, A Piacentini, J Pauls, DL Rasmussen, SA Shugart, YY Nestadt, G Samuels, J AF Riddle, Mark A. Maher, Brion S. Wang, Ying Grados, Marco Bienvenu, O. Joseph Goes, Fernando S. Cullen, Bernadette Murphy, Dennis L. Rauch, Scott L. Greenberg, Benjamin D. Knowles, James A. McCracken, James T. Pinto, Anthony Piacentini, John Pauls, David L. Rasmussen, Steven A. Shugart, Yin Yao Nestadt, Gerald Samuels, Jack TI OBSESSIVE-COMPULSIVE PERSONALITY DISORDER: EVIDENCE FOR TWO DIMENSIONS SO DEPRESSION AND ANXIETY LA English DT Article DE obsessive-compulsive disorder; personality disorder; genetic; assessment and diagnosis; hoarding ID OCD COLLABORATIVE GENETICS; GENOTYPING ERRORS; COMMUNITY SAMPLE; DSM-IV; PREVALENCE; IDENTIFICATION; ASSOCIATION; RATIONALE; FAMILY AB BackgroundTo determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic linkage. MethodsParticipants were selected from 844 adults assessed with the Structured Instrument for the Diagnosis of DSM-IV Personality Disorders (SIDP) in the OCD Collaborative Genetics Study (OCGS) that targeted families with obsessive-compulsive disorder (OCD) affected sibling pairs. We conducted an exploratory factor analysis, which included the eight SIDP-derived DSM-IV OCPD traits and the indecision trait from the DSM-III, assessed clinical correlates, and estimated sib-sib correlations to evaluate familiality of the factors. Using MERLIN and MINX, we performed genome-wide quantitative trait locus (QTL) linkage analysis to test for allele sharing among individuals. ResultsTwo factors were identified: Factor 1: order/control (perfectionism, excessive devotion to work, overconscientiousness, reluctance to delegate, and rigidity); and Factor 2: hoarding/indecision (inability to discard and indecisiveness). Factor 1 score was associated with poor insight, whereas Factor 2 score was associated with task incompletion. A significant sib-sib correlation was found for Factor 2 (rICC = .354, P < .0001) but not Factor 1 (rICC = .129, P = .084). The linkage findings were different for the two factors. When Factor 2 was analyzed as a quantitative trait, a strong signal was detected on chromosome 10 at marker d10s1221: KAC LOD = 2.83, P = .0002; and marker d10s1225: KAC LOD = 1.35, P = .006. ConclusionsThe results indicate two factors of OCPD, order/control and hoarding/indecision. The hoarding/indecision factor is familial and shows modest linkage to a region on chromosome 10. C1 [Riddle, Mark A.; Wang, Ying; Grados, Marco; Bienvenu, O. Joseph; Goes, Fernando S.; Cullen, Bernadette; Nestadt, Gerald; Samuels, Jack] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 550 N Broadway,Suite 203, Baltimore, MD 21205 USA. [Maher, Brion S.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, 550 N Broadway,Suite 203, Baltimore, MD 21205 USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Rauch, Scott L.] Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Boston, MA 02115 USA. [Greenberg, Benjamin D.; Rasmussen, Steven A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Knowles, James A.] Univ So Calif, Sch Med, Dept Psychiat, Los Angeles, CA USA. [McCracken, James T.; Piacentini, John] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Pinto, Anthony] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Pauls, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Psychiat & Neurodev Genet Unit, Boston, MA USA. [Shugart, Yin Yao] NIMH, Unit Stat Genom, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Riddle, MA (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 550 N Broadway,Suite 203, Baltimore, MD 21205 USA.; Riddle, MA (reprint author), Johns Hopkins Univ, Sch Med, 550 N Broadway,Suite 203, Baltimore, MD 21205 USA. EM mriddle1@jhmi.edu RI Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU National Institute of Mental Health; NIH; NARSAD; Seaside Therapeutics; Roche; Shire; Dart Neuroscience [R01MH50214, MH071507, MH079489, MH079487, MH079488, MH079494] FX Contract grant sponsor: National Institute of Mental Health; Contract grant sponsor: NIH; Contract grant sponsor: NARSAD; Contract grant sponsor: Seaside Therapeutics; Contract grant sponsor: Roche; Contract grant sponsor: Shire Contract grant sponsor: Dart Neuroscience; Contract grant numbers: R01MH50214, MH071507, MH079489, MH079487, MH079488, and MH079494. NR 42 TC 1 Z9 1 U1 6 U2 14 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 FEB PY 2016 VL 33 IS 2 BP 128 EP 135 DI 10.1002/da.22452 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DC2SE UT WOS:000369065800004 PM 26594839 ER PT J AU Boes, AD Caruso, P Duhaime, AC Fischl, B AF Boes, Aaron D. Caruso, Paul Duhaime, Ann-Christine Fischl, Bruce TI FreeSurfer is useful for early detection of Rasmussen's encephalitis prior to obvious atrophy SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Editorial Material C1 [Boes, Aaron D.] Harvard Univ, Sch Med, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat,Div Co, Boston, MA 02114 USA. [Boes, Aaron D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Boes, Aaron D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Neurol, Boston, MA 02114 USA. [Caruso, Paul; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Duhaime, Ann-Christine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Neurosurg, Boston, MA 02114 USA. [Fischl, Bruce] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Boes, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Neurol, Boston, MA 02114 USA. EM aboes@partners.org FU NINDS NIH HHS [R25 NS065743, 5R25NS065743-05] NR 2 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 EI 1469-8749 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD FEB PY 2016 VL 58 IS 2 BP 209 EP 210 DI 10.1111/dmcn.12847 PG 2 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA DC1MV UT WOS:000368981300027 PM 26174006 ER PT J AU Jaffa, MA Luttrell, D Schmaier, AH Klein, RL Lopes-Virella, M Luttrell, LM Jaffa, AA AF Jaffa, Miran A. Luttrell, Deirdre Schmaier, Alvin H. Klein, Richard L. Lopes-Virella, Maria Luttrell, Louis M. Jaffa, Ayad A. CA DCC EDIC Res Grp TI Plasma Prekallikrein Is Associated With Carotid Intima-Media Thickness in Type 1 Diabetes SO DIABETES LA English DT Article ID KALLIKREIN-KININ SYSTEM; VASCULAR SMOOTH-MUSCLE; MACROVASCULAR COMPLICATIONS; CONTACT ACTIVATION; ENDOTHELIAL-CELLS; PROLYLCARBOXYPEPTIDASE; INFLAMMATION; NEPHROPATHY; PROGRESSION; MECHANISM AB The hypothesis that plasma prekallikrein (PK) is a risk factor for the development of vascular complications was assessed in a study using the Diabetes Control and Complications Trial (DCCT)/Epidemiology and Diabetes Interventions and Complications (EDIC) cohort of subjects with type 1 diabetes. The circulating levels of plasma PK activity were measured in the plasma of 636 subjects with type 1 diabetes (EDIC years 3-5). Common and internal carotid intima-media thickness (IMT) were measured by B-mode ultrasonography in EDIC years 1 and 6. Plasma PK levels were positively and significantly associated with BMI, hemoglobin A(1c), systolic blood pressure, total cholesterol, LDL cholesterol, and triglycerides but not with age, sex, duration of diabetes, or HDL cholesterol. Univariate and multivariable statistical models after controlling for other risk factors consistently demonstrated a positive association between plasma PK and progression of internal carotid IMT. Multivariate analysis using a general linear model showed plasma PK to be significantly associated with progression of both internal and combined IMT (Wilks Lambda P value of 0.005). In addition, the mean internal carotid IMT levels were higher in subjects with plasma PK levels in the highest 10th percentile compared with subjects with plasma PK levels in the lower 10th percentile (P = 0.048). These novel findings implicate plasma PK as a risk factor for vascular disease in type 1 diabetes. C1 [Jaffa, Miran A.] Amer Univ Beirut, Fac Hlth Sci, Epidemiol & Populat Hlth Dept, Beirut, Lebanon. [Luttrell, Deirdre; Klein, Richard L.; Lopes-Virella, Maria; Luttrell, Louis M.; Jaffa, Ayad A.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Schmaier, Alvin H.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Klein, Richard L.] Ralph H Johnson Dept Vet Affairs Med Ctr, Res Serv, Charleston, SC 29403 USA. [Jaffa, Ayad A.] Amer Univ Beirut, Dept Biochem & Mol Genet, Fac Med, Beirut, Lebanon. RP Jaffa, AA (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.; Jaffa, AA (reprint author), Amer Univ Beirut, Dept Biochem & Mol Genet, Fac Med, Beirut, Lebanon. EM aj24@aub.edu.lb FU National Institutes for Health [HL-052779, HL-055782, HL-077192, HL-087986]; Division of Diabetes, Endocrinology, and Metabolic Diseases, National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX This work was supported by National Institutes for Health research grants HL-052779 (to A.H.S.), HL-055782 (to M.L.-V.), and HL-077192 and HL-087986 (to A.A.J.). The DCCT/EDIC was sponsored through research contracts from the Division of Diabetes, Endocrinology, and Metabolic Diseases, National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 24 TC 1 Z9 1 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD FEB PY 2016 VL 65 IS 2 BP 498 EP 502 DI 10.2337/db15-0930 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DC1HS UT WOS:000368968000020 PM 26603531 ER PT J AU Hivert, MF Christophi, CA Franks, PW Jablonski, KA Ehrmann, DA Kahn, SE Horton, ES Pollin, TI Mather, KJ Perreault, L Barrett-Connor, E Knowler, WC Florez, JC AF Hivert, Marie-France Christophi, Costas A. Franks, Paul W. Jablonski, Kathleen A. Ehrmann, David A. Kahn, Steven E. Horton, Edward S. Pollin, Toni I. Mather, Kieren J. Perreault, Leigh Barrett-Connor, Elizabeth Knowler, William C. Florez, Jose C. CA Diabetes Prevention Program Res TI Lifestyle and Metformin Ameliorate Insulin Sensitivity Independently of the Genetic Burden of Established Insulin Resistance Variants in Diabetes Prevention Program Participants SO DIABETES LA English DT Article ID BETA-CELL DYSFUNCTION; RELATIVE CONTRIBUTIONS; GLUCOSE-TOLERANCE; GLYCEMIC TRAITS; INTERVENTION; HOMEOSTASIS; SECRETION AB Large genome-wide association studies of glycemic traits have identified genetics variants that are associated with insulin resistance (IR) in the general population. It is unknown whether people with genetic enrichment for these IR variants respond differently to interventions that aim to improve insulin sensitivity. We built a genetic risk score (GRS) based on 17 established IR variants and effect sizes (weighted IR-GRS) in 2,713 participants of the Diabetes Prevention Program (DPP) with genetic consent. We tested associations between the weighted IR-GRS and insulin sensitivity index (ISI) at baseline in all participants, and with change in ISI over 1 year of follow-up in the DPP intervention (metformin and lifestyle) and control (placebo) arms. All models were adjusted for age, sex, ethnicity, and waist circumference at baseline (plus baseline ISI for 1-year ISI change models). A higher IR-GRS was associated with lower baseline ISI (beta= -0.754 [SE = 0.229] log-ISI per unit, P = 0.001 in fully adjusted models). There was no differential effect of treatment for the association between the IR-GRS on the change in ISI; higher IR-GRS was associated with an attenuation in ISI improvement over 1 year (beta = -0.520 [SE = 0.233], P = 0.03 in fully adjusted models; all treatment arms). Lifestyle intervention and metformin treatment improved the ISI, regardless of the genetic burden of IR variants. C1 [Hivert, Marie-France] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA 02115 USA. [Hivert, Marie-France; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Christophi, Costas A.; Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Franks, Paul W.] Lund Univ, Dept Clin Sci, Ctr Diabet, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Div Med, Umea, Sweden. [Ehrmann, David A.] Univ Chicago, Sch Med, Dept Med, Chicago, IL 60637 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Horton, Edward S.] Joslin Diabet Ctr, Sect Clin Behav & Outcomes Res, Boston, MA 02215 USA. [Horton, Edward S.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Pollin, Toni I.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Pollin, Toni I.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Pollin, Toni I.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Mather, Kieren J.] Indiana Univ Sch Med, Dept Med, Div Endocrinol, Indianapolis, IN 46202 USA. [Perreault, Leigh] Univ Colorado, Dept Med, Div Endocrinol Metab & Diabet, Anschutz Med Campus, Aurora, CO USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Epidemiol, La Jolla, CA 92093 USA. [Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.; Florez, JC (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.; Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.; Florez, JC (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. EM dppmail@bsc.gwu.edu OI Kahn, Steven/0000-0001-7307-9002 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health [DK-48489]; NIDDK; Indian Health Service; National Institute of Child Health and Human Development; National Institute on Aging; National Eye Institute; National Heart, Lung, and Blood Institute; Office of Research on Women's Health; National Institute on Minority Health and Health Disparities; Centers for Disease Control and Prevention; American Diabetes Association FX During the DPPOS, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding (grant DK-48489) to the clinical centers and the Coordinating Center for the design and conduct of the study, and The collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development; the National Institute on Aging; the National Eye Institute; the National Heart, Lung, and Blood Institute; the Office of Research on Women's Health; the National Institute on Minority Health and Health Disparities; the Centers for Disease Control and Prevention; and the American Diabetes Association. Lipha (Merck-Sante) provided medication, and LifeScan, Inc. donated materials during the DPP and DPPOS. NR 20 TC 4 Z9 4 U1 2 U2 4 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 FEB PY 2016 VL 65 IS 2 BP 520 EP 526 DI 10.2337/db15-0950 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DC1HS UT WOS:000368968000023 PM 26525880 ER PT J AU Kaunitz, JD AF Kaunitz, Jonathan D. TI The Doppler Effect: A Century from Red Shift to Red Spot SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID BLOOD-FLOW; ULTRASOUND C1 [Kaunitz, Jonathan D.] VA Greater Los Angeles Healthcare Syst, Bldg 114-217E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Bldg 114-217E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), VA Greater Los Angeles Healthcare Syst, Bldg 114-217E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.; Kaunitz, JD (reprint author), Univ Calif Los Angeles, Sch Med, Bldg 114-217E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU BLRD VA [I01 BX001245]; Intramural VA [VA999999]; NIDDK NIH HHS [R01 DK054221] NR 12 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2016 VL 61 IS 2 BP 340 EP 341 DI 10.1007/s10620-015-3998-9 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DC1XR UT WOS:000369012100006 PM 26745970 ER PT J AU Sahora, K Crippa, S Zamboni, G Ferrone, C Warshaw, AL Lillemoe, K Mino-Kenudson, M Falconi, M Fernandez-del Castillo, C AF Sahora, K. Crippa, S. Zamboni, G. Ferrone, C. Warshaw, A. L. Lillemoe, K. Mino-Kenudson, M. Falconi, M. Fernandez-del Castillo, C. TI Intraductal papillary mucinous neoplasms of the pancreas with concurrent pancreatic and periampullary neoplasms SO EJSO LA English DT Article DE Pancreas; Intraductal papillary mucinous noeplasm; Concurrent neoplasm; Pancreatic cancer ID TERM-FOLLOW-UP; BRANCH-DUCT; CARCINOMA; CONSENSUS; CONCOMITANT; PREDICTORS; RESECTION; TUMOR; IPMN; ADENOCARCINOMAS AB Background: Intraductal papillary mucinous neoplasms (IPMN) have been reported to be associated with concurrent, distinct pancreatic ductal adenocarcinoma (con-PDAC) in about 8% (range, 4-10%) of resected branch duct (BD) lesions. In addition, other pancreatic and ampullary tumors are occasionally diagnosed with IPMN in patients undergoing pancreatic surgery. The objective of this study is to describe the prevalence, clinicopathologic characteristics and prognosis of IPMN with concurrent pancreatic and ampullary neoplasms, especially con-PDAC. Methods: The combined databases of pancreatic resections from the Massachusetts General Hospital and the Negrar Hospital, Italy, were analyzed for patients who had been diagnosed with IPMN and concurrent pancreatic or ampullary neoplasms. Results: 2762 patients underwent pancreatic surgery from January 2000 to December 2012. Sixteen percent (n = 441) had pathologically confirmed IPMN and 11% of these (n = 50) had a different distinct synchronous pancreatic neoplasm. The majority of these, 62%, were con-PDAC, followed by neuroendocrine neoplasms (10%) and ampullary carcinoma (10%). Less frequently, mucinous (6%) as well as serous cystic neoplasms (6%), adenosquamous carcinoma (4%) and distal bile duct cancer (2%) were diagnosed. Among all patients with synchronous neoplasms, 66% harbored BD-IPMN, 28% combined IPMN and 6% main duct IPMN. Abdominal pain and/or jaundice were the leading symptoms in half of patients. Conclusion: IPMN, mainly BD-IPMN, are associated with con-PDAC in about 7% of patients and account for 62% of all concurrent pancreatic/ampullary neoplasms. Other synchronous neoplasms may be found sporadically with IPMN without a suspected association. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Sahora, K.; Ferrone, C.; Warshaw, A. L.; Lillemoe, K.; Fernandez-del Castillo, C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sahora, K.; Ferrone, C.; Warshaw, A. L.; Lillemoe, K.; Mino-Kenudson, M.; Fernandez-del Castillo, C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Crippa, S.; Falconi, M.] Osped Sacro Cuore Don Calabria, Dept Surg, Negrar, VR, Italy. [Crippa, S.; Zamboni, G.; Falconi, M.] Osped Sacro Cuore Don Calabria, Dept Pathol, Negrar, VR, Italy. [Crippa, S.; Falconi, M.] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Div Pancreat Surg, Milan, Italy. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Surg,Med Sch, 460,15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org OI Zamboni, Giuseppe/0000-0001-7428-4673; Falconi, Massimo/0000-0001-9654-7243 NR 40 TC 2 Z9 2 U1 1 U2 3 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 FEB PY 2016 VL 42 IS 2 BP 197 EP 204 DI 10.1016/j.ejso.2015.10.014 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA DC1GP UT WOS:000368965100006 PM 26687069 ER PT J AU Flinn, IW Bartlett, NL Blum, KA Ardeshna, KM LaCasce, AS Flowers, CR Shustov, AR Thress, KS Mitchell, P Zheng, F Skolnik, JM Friedberg, JW AF Flinn, Ian W. Bartlett, Nancy L. Blum, Kristie A. Ardeshna, Kirit M. LaCasce, Ann S. Flowers, Christopher R. Shustov, Andrei R. Thress, Kenneth S. Mitchell, Patrick Zheng, Fred Skolnik, Jeffrey M. Friedberg, Jonathan W. TI A phase II trial to evaluate the efficacy of fostamatinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE DLBCL; Syk inhibitor; B-cell receptor; Phase II; Clinical trial ID GENE-EXPRESSION; MALIGNANT-LYMPHOMA; CHEMOTHERAPY; THERAPY; RITUXIMAB; SURVIVAL; RECEPTOR; SUBTYPES; CHOP; SYK AB Purpose: To assess the safety and efficacy of fostamatinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Experimental design: Relapsed or refractory DLBCL patients originally received the oral spleen tyrosine kinase inhibitor, fostamatinib in a two-arm, randomised, double-blinded manner at either 100 mg twice a day (BID) or 200 mg BID until disease progression or unacceptable toxicity. The primary objective was to assess the overall response rate (ORR). Preliminary analysis showed limited efficacy and all subsequent patients were treated at 200 mg BID. Previously randomised patients were unblinded and given the opportunity to receive 200 mg BID. Results: Sixty-eight patients were treated (47 at 200 mg BID, 21 at 100 mg BID). Cell of origin analysis showed 58% germinal B-cell (GCB) origin, 30% activated B-cell (ABC) origin and 12% with an intermediate cell of origin signature. The most common treatment-related adverse events of all patients were diarrhoea (21% total, 6% grade 3/4), nausea (19% total, 3% grade 3/4), and, fatigue (18% total, 9% grade 3/4). The ORR rate was 3% across both arms and clinical benefit (>= stable disease) was achieved for 13% of all patients. The cell of origin for patients with clinical benefit was GCB (4 patients), intermediate (4 patients) or unknown (1 patient). None of the patients with clinical benefit had ABC genotype. Conclusions: While fostamatinib was generally well tolerated in this patient population, efficacy at these doses and schedule was poor. Unlike data with other B-cell antigen receptor pathway inhibitors, responses were not observed in the ABC genotype. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Flinn, Ian W.] Sarah Cannon Res Inst, Tennessee Oncol, Nashville, TN USA. [Bartlett, Nancy L.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Blum, Kristie A.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Ardeshna, Kirit M.] UCL, Sarah Cannon Res Inst United Kingdom, London, England. [LaCasce, Ann S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Flowers, Christopher R.] Winship Canc Inst, Atlanta, GA USA. [Shustov, Andrei R.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Thress, Kenneth S.; Mitchell, Patrick] AstraZeneca, Waltham, MA USA. [Zheng, Fred; Skolnik, Jeffrey M.] AstraZeneca, Wilmington, DE USA. [Friedberg, Jonathan W.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Zheng, Fred] GlaxoSmithKline, Brentford, England. [Skolnik, Jeffrey M.] TetraL Pharmaceut, Malvern, PA USA. RP Flinn, IW (reprint author), Sarah Cannon Res Inst, 250 25th Ave North, Nashville, TN 37203 USA. EM iflinn@tnonc.com RI Flowers, Christopher/F-1953-2010 OI Flowers, Christopher/0000-0002-9524-3990 NR 32 TC 6 Z9 7 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD FEB PY 2016 VL 54 BP 11 EP 17 DI 10.1016/j.ejca.2015.10.005 PG 7 WC Oncology SC Oncology GA DC3WQ UT WOS:000369150000002 PM 26707592 ER PT J AU Wong, JC Linn, KA Shinohara, RT Mateen, FJ AF Wong, J. C. Linn, K. A. Shinohara, R. T. Mateen, F. J. TI Traumatic brain injury in Africa in 2050: a modeling study SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE acute brain injury; adolescent; adult; epidemiology ID KENYA AB Background and purposeOur aim was to provide estimates of traumatic brain injury (TBI) in 2050 for the African population by region, sex and age strata. MethodsA literature search was performed in October 2014 in PubMed for population-based studies of TBI in different geographical locations. Articles were selected from Kenya (model 1), New Zealand (model 2) and the USA (model 3). In model 1, rates of road traffic injury in Kenya were used to estimate TBI rates in the African continent. Models 2 and 3 used existing TBI incidence estimates from other locations to estimate the burden of TBI for Africa in 2050. The 2050 African population, as projected by the United Nations, was used as a base population. ResultsBased on rates from model 1, the estimated total TBI count in Africa in 2050 is 5.98 0.03 million, with the highest count in eastern (2.04 +/- 0.01 million) and lowest count in southern (0.15 +/- 0.00 million) Africa. A higher TBI count is predicted by models 2 (14.25 +/- 0.75 million) and 3 (10.40 +/- 0.02 million). Estimated TBI count is highest for males aged 15-34 (5.47 +/- 0.55 million in model 2 and 3.21 +/- 0.13 million in model 3). ConclusionsProjected estimates of TBI in Africa are high, with a burden of anywhere between approximately 6 and 14 million new cases in 2050. This emphasizes the importance of developing accurate surveillance systems of TBI at a population level and public health measures to mitigate the risk and burden of TBI. C1 [Wong, J. C.; Mateen, F. J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wong, J. C.; Mateen, F. J.] Harvard Univ, Sch Med, Boston, MA USA. [Wong, J. C.] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. [Linn, K. A.; Shinohara, R. T.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Neurol Clin Res Inst, Dept Neurol, 165 Cambridge St,627, Boston, MA 02114 USA. EM fmateen@partners.org NR 16 TC 1 Z9 1 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD FEB PY 2016 VL 23 IS 2 BP 382 EP 386 DI 10.1111/ene.12877 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DB8WE UT WOS:000368797100034 PM 26435298 ER PT J AU Kimball, AB AF Kimball, Alexa B. TI New insights into diagnosis of HS & classifications SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT Joint CHSF/HSF/EHSF Pre-WCD Hidradenitis Suppurativa Symposium CY JUN 06, 2015 CL Vancouver, CANADA SP CHSF, HSF, EHSF C1 [Kimball, Alexa B.] Harvard Univ, Sch Med, Boston, MA USA. [Kimball, Alexa B.] 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 0906-6705 EI 1600-0625 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2016 VL 25 SU 1 MA 3 BP 7 EP 7 PG 1 WC Dermatology SC Dermatology GA DB9OR UT WOS:000368846400005 ER PT J AU Schoenfeld, P Dominitz, JA AF Schoenfeld, Philip Dominitz, Jason A. TI No Polyp Left Behind: Defining Bowel Preparation Adequacy to Avoid Missed Polyps SO GASTROENTEROLOGY LA English DT Editorial Material ID SOCIETY-TASK-FORCE; ADENOMA DETECTION RATE; AVERAGE-RISK PATIENTS; COLORECTAL-CANCER; PREPARATION SCALE; COLONOSCOPY; RECOMMENDATIONS; IMPACT; SURVEILLANCE; CLEANLINESS C1 [Schoenfeld, Philip] Univ Michigan, Sch Med, Ann Arbor Vet Hlth Care Syst, Ann Arbor, MI USA. [Dominitz, Jason A.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Schoenfeld, P (reprint author), Univ Michigan, Sch Med, Med, Room 111-D,2215 Fuller Rd, Ann Arbor, MI USA. NR 23 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 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2016 VL 150 IS 2 BP 303 EP 306 DI 10.1053/j.gastro.2015.12.024 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB6MU UT WOS:000368629900010 PM 26713765 ER PT J AU Su, F Yu, L Berry, K Liou, IW Landis, CS Rayhill, SC Reyes, JD Ioannou, GN AF Su, Feng Yu, Lei Berry, Kristin Liou, Iris W. Landis, Charles S. Rayhill, Stephen C. Reyes, Jorge D. Ioannou, George N. TI Aging of Liver Transplant Registrants and Recipients: Trends and Impact on Waitlist Outcomes, Post-Transplantation Outcomes, and Transplant-Related Survival Benefit SO GASTROENTEROLOGY LA English DT Article DE Waitlist Outcomes; Post-Transplantation Outcomes; Transplant-Related Survival Benefit ID C VIRUS-INFECTION; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; WAITING-LIST; NONALCOHOLIC STEATOHEPATITIS; CANDIDATES; MORTALITY; OLDER; AGE; DISEASE AB BACKGROUND & AIMS: Epidemiologic factors have generated increased demand for liver transplantation among older patients. We aimed to describe trends in age among liver transplant registrants and recipients and the effect of age on waitlist and post-transplantation outcomes and on transplant-related survival benefit. METHODS: We obtained data from the United Network for Organ Sharing on adults who were listed for liver transplantation (N = 122,606) or underwent liver transplantation (N = 60,820) from 2002 to 2014 in the United States. Competing risks analysis was used to model waitlist outcomes and Cox proportional hazards analysis to model post-transplantation survival. These models were also used to estimate 5-year transplant-related survival benefit for different age groups, calculated as the difference between waitlist and post-transplantation life expectancy. RESULTS: Between 2002 and 2014, the mean age of liver transplant registrants increased from 51.2 to 55.7 years, with a more prominent increase in hepatitis C virus-positive (50.9 - 57.9 years) than hepatitis C virus-negative (51.3 - 54.3 years) registrants. The proportion of registrants aged >= 60 years increased from 19% to 41%. In hepatitis C virus-negative patients, aging trends were driven by increasing proportions of patients with hepatocellular carcinoma or nonalcoholic steatohepatitis. Among transplant registrants, increasing age was associated with increasing mortality before transplantation and decreasing likelihood of transplantation. Among transplant recipients, increasing age was associated with increasing post-transplantation mortality. There was little difference in 5-year transplant-related survival benefit between different age groups who had the same Model for EndStage Liver Disease score. CONCLUSIONS: Dramatic aging of liver transplant registrants and recipients occurred from 2002 to 2014, driven by aging of the hepatitis C virus - positive cohort and increased prevalence of nonalcoholic steatohepatitis and hepatocellular carcinoma. Increasing age does not affect transplant-related survival benefit substantially because age diminishes both post-transplantation survival and waitlist survival approximately equally. C1 [Su, Feng] Univ Washington, Dept Med, Div Internal Med, Seattle, WA USA. [Yu, Lei; Liou, Iris W.; Landis, Charles S.; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA USA. [Yu, Lei; Liou, Iris W.; Landis, Charles S.; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Berry, Kristin] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA USA. [Rayhill, Stephen C.; Reyes, Jorge D.] Univ Washington, Dept Surg, Div Transplant Surg, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol, S-111 Gastro 1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Research and Development, Veterans Affairs Puget Sound Healthcare System; Health Resources and Services Administration [231-00-0115] FX This study was funded byResearch and Development, Veterans Affairs Puget Sound Healthcare System. This work was supported in part by Health Resources and Services Administration contract 231-00-0115. NR 42 TC 4 Z9 4 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 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2016 VL 150 IS 2 BP 441 EP + DI 10.1053/j.gastro.2015.10.043 PG 19 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB6MU UT WOS:000368629900031 PM 26522262 ER PT J AU Berry, K Ioannou, GN AF Berry, Kristin Ioannou, George N. TI Estimation of Liver Transplant Related Survival Benefit: the Devil Is in The Details Reply SO GASTROENTEROLOGY LA English DT Letter ID HEPATOCELLULAR-CARCINOMA C1 [Berry, Kristin; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA USA. [Ioannou, George N.] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA USA. RP Berry, K (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 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 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2016 VL 150 IS 2 BP 535 EP 537 DI 10.1053/j.gastro.2015.12.030 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB6MU UT WOS:000368629900042 PM 26718174 ER PT J AU Schneider, JL Davis, J Kauffman, TL Reiss, JA McGinley, C Arnold, K Zepp, J Gilmore, M Muessig, KR Syngal, S Acheson, L Wiesner, GL Peterson, SK Goddard, KAB AF Schneider, Jennifer L. Davis, James Kauffman, Tia L. Reiss, Jacob A. McGinley, Cheryl Arnold, Kathleen Zepp, Jamilyn Gilmore, Marian Muessig, Kristin R. Syngal, Sapna Acheson, Louise Wiesner, Georgia L. Peterson, Susan K. Goddard, Katrina A. B. TI Stakeholder perspectives on implementing a universal Lynch syndrome screening program: a qualitative study of early barriers and facilitators SO GENETICS IN MEDICINE LA English DT Article DE implementation factors; stakeholder interviews; universal Lynch syndrome screening ID NONPOLYPOSIS COLORECTAL-CANCER; GENETIC TESTING STRATEGIES; MICROSATELLITE INSTABILITY; REDUCING MORBIDITY; COST-EFFECTIVENESS; MUTATIONS; IMMUNOHISTOCHEMISTRY; FEASIBILITY; MORTALITY; TUMORS AB Purpose: Evidence-based guidelines recommend that all newly diagnosed colon cancer be screened for Lynch syndrome (LS), but best practices for implementing universal tumor screening have not been extensively studied. We interviewed a range of stakeholders in an integrated health-care system to identify initial factors that might promote or hinder the successful implementation of a universal LS screening program. Methods: We conducted interviews with health-plan leaders, managers, and staff. Interviews were audio-recorded and transcribed. Thematic analysis began with a grounded approach and was also guided by the Practical Robust Implementation and Sustainability Model (PRISM). Results: We completed 14 interviews with leaders/managers and staff representing involved clinical and health-plan departments. Although stakeholders supported the concept of universal screening, they identified several internal (organizational) and external (environment) factors that promote or hinder implementation. Facilitating factors included perceived benefits of screening for patients and organization, collaboration between departments, and availability of organizational resources. Barriers were also identified, including: lack of awareness of guidelines, lack of guideline clarity, staffing and program "ownership" concerns, and cost uncertainties. Analysis also revealed nine important infrastructure-type considerations for successful implementation. Conclusion: We found that clinical, laboratory, and administrative departments supported universal tumor screening for LS. Requirements for successful implementation may include interdepartmental collaboration and communication, patient and provider/staff education, and significant infrastructure and resource support related to laboratory processing and systems for electronic ordering and tracking. C1 [Schneider, Jennifer L.; Davis, James; Kauffman, Tia L.; Reiss, Jacob A.; McGinley, Cheryl; Arnold, Kathleen; Muessig, Kristin R.; Goddard, Katrina A. B.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. [Zepp, Jamilyn; Gilmore, Marian] Kaiser Permanente Northwest, Northwest Permanente, Portland, OR USA. [Syngal, Sapna] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Acheson, Louise] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Wiesner, Georgia L.] Vanderbilt Ingram Canc Ctr, Vanderbilt Hereditary Canc Program, Nashville, TN USA. [Peterson, Susan K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Schneider, JL (reprint author), Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. EM Jennifer.L.Schneider@kpchr.org FU National Institute of Health [5R01CA140377] FX This work was supported through a grant by the National Institute of Health: 5R01CA140377 (K.A.B.G.). The authors thank Jill Pope for editorial support and Robin Daily and Elizabeth Sheeley for administrative assistance. NR 34 TC 1 Z9 1 U1 0 U2 2 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 FEB PY 2016 VL 18 IS 2 BP 152 EP 161 DI 10.1038/gim.2015.43 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA DC4EQ UT WOS:000369173600008 PM 25880440 ER PT J AU Koyfman, SA Cooper, JS Beitler, JJ Busse, PM Jones, CU McDonald, MW Quon, H Ridge, JA Saba, NF Salama, JK Siddiqui, F Smith, RV Worden, F Yao, M Yom, SS AF Koyfman, Shlomo A. Cooper, Jay S. Beitler, Jonathan J. Busse, Paul M. Jones, Christopher U. McDonald, Mark W. Quon, Harry Ridge, John A. Saba, Nabil F. Salama, Joseph K. Siddiqui, Farzan Smith, Richard V. Worden, Francis Yao, Min Yom, Sue S. TI ACR Appropriateness Criteria((R)) Aggressive Nonmelanomatous Skin Cancer of the Head and Neck SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE Appropriateness Criteria; nonmelanomatous skin cancer; head neck; high risk; radiotherapy ID SQUAMOUS-CELL CARCINOMA; ORGAN TRANSPLANT RECIPIENTS; ADVANCED BASAL-CELL; X-RAY THERAPY; PERINEURAL INVASION; CUTANEOUS HEAD; PHASE-II; RADIOTHERAPY; FACE; CHEMOTHERAPY AB BackgroundAggressive nonmelanomatous skin cancer (NMSC) of the head and neck presents an increasingly common therapeutic challenge for which prospective clinical trials are lacking. MethodsThe 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. ResultsThe American College of Radiology Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for guiding management of aggressive NMSC. ConclusionMultidisciplinary assessment is vital to guiding the ideal use of surgery, radiation, and systemic therapy in this disease. (c) 2016 Wiley Periodicals, Inc. Head Neck38: 175-182, 2016 C1 [Koyfman, Shlomo A.] Cleveland Clin, Cleveland, OH 44106 USA. [Cooper, Jay S.] Maimonides Canc Ctr, Brooklyn, NY USA. [Beitler, Jonathan J.] Emory Univ, Sch Med, Atlanta, GA USA. [Busse, Paul M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jones, Christopher U.] Radiol Associates Sacramento, Sacramento, CA USA. [McDonald, Mark W.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Quon, Harry] Johns Hopkins Univ, Baltimore, MD USA. [Ridge, John A.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Saba, Nabil F.] Emory Univ, Atlanta, GA 30322 USA. [Salama, Joseph K.] Duke Univ, Durham, NC USA. [Siddiqui, Farzan] Henry Ford Hlth Syst, Detroit, MI USA. [Smith, Richard V.] Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. [Worden, Francis] Univ Michigan, Ann Arbor, MI 48109 USA. [Yao, Min] Univ Hosp, Case Med Ctr, Cleveland, OH USA. [Yom, Sue S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Koyfman, SA (reprint author), Cleveland Clin Fdn, Dept Radiat Oncol, 9500 Euclid Ave,Desk T28, Cleveland, OH 44195 USA. EM Koyfmas@ccf.org NR 37 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD FEB PY 2016 VL 38 IS 2 BP 175 EP 182 DI 10.1002/hed.24171 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DB7ZB UT WOS:000368735100009 PM 26791005 ER PT J AU Varvares, MA Walker, RJ AF Varvares, Mark A. Walker, Ronald J. TI Letter to the editor regarding: Management of invasive well-differentiated thyroid cancer: An American Head and Neck Society Consensus Statement SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Letter C1 [Varvares, Mark A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Cambridge, MA 02138 USA. [Varvares, Mark A.; 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 Otorhinolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM Mark_Varvares@meei.harvard.edu NR 3 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD FEB PY 2016 VL 38 IS 2 BP 328 EP 329 DI 10.1002/hed.24288 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DB7ZB UT WOS:000368735100032 PM 26667782 ER PT J AU Mebazaa, A Tolppanen, H Mueller, C Lassus, J DiSomma, S Baksyte, G Cecconi, M Choi, DJ Solal, AC Christ, M Masip, J Arrigo, M Nouira, S Ojji, D Peacock, F Richards, M Sato, N Sliwa, K Spinar, J Thiele, H Yilmaz, MB Januzzi, J AF Mebazaa, A. Tolppanen, H. Mueller, C. Lassus, J. DiSomma, S. Baksyte, G. Cecconi, M. Choi, D. J. Solal, A. Cohen Christ, M. Masip, J. Arrigo, M. Nouira, S. Ojji, D. Peacock, F. Richards, M. Sato, N. Sliwa, K. Spinar, J. Thiele, H. Yilmaz, M. B. Januzzi, J. TI Acute heart failure and cardiogenic shock: a multidisciplinary practical guidance SO INTENSIVE CARE MEDICINE LA English DT Review DE Heart failure; Cardiogenic shock; Emergency; Treatment ID ACUTE MYOCARDIAL-INFARCTION; COLLEGE-OF-CARDIOLOGY; NATRIURETIC PEPTIDE LEVELS; RIGHT-VENTRICULAR FAILURE; INTENSIVE-CARE MEDICINE; 2013 ACCF/AHA GUIDELINE; ASSOCIATION TASK-FORCE; PULMONARY-EDEMA; EUROPEAN-SOCIETY; NONINVASIVE VENTILATION AB Purpose: Acute heart failure (AHF) causes high burden of mortality, morbidity, and repeated hospitalizations worldwide. This guidance paper describes the tailored treatment approaches of different clinical scenarios of AHF and CS, focusing on the needs of professionals working in intensive care settings. Results: Tissue congestion and hypoperfusion are the two leading mechanisms of end-organ injury and dysfunction, which are associated with worse outcome in AHF. Diagnosis of AHF is based on clinical assessment, measurement of natriuretic peptides, and imaging modalities. Simultaneously, emphasis should be given in rapidly identifying the underlying trigger of AHF and assessing severity of AHF, as well as in recognizing end-organ injuries. Early initiation of effective treatment is associated with superior outcomes. Oxygen, diuretics, and vasodilators are the key therapies for the initial treatment of AHF. In case of respiratory distress, non-invasive ventilation with pressure support should be promptly started. In patients with severe forms of AHF with cardiogenic shock (CS), inotropes are recommended to achieve hemodynamic stability and restore tissue perfusion. In refractory CS, when hemodynamic stabilization is not achieved, the use of mechanical support with assist devices should be considered early, before the development of irreversible end-organ injuries. Conclusion: A multidisciplinary approach along the entire patient journey from pre-hospital care to hospital discharge is needed to ensure early recognition, risk stratification, and the benefit of available therapies. Medical management should be planned according to the underlying mechanisms of various clinical scenarios of AHF. C1 [Mebazaa, A.; Tolppanen, H.; Solal, A. Cohen; Arrigo, M.] INSERM, U942, Paris, France. [Mebazaa, A.; Solal, A. Cohen] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Mebazaa, A.] Hop Lariboisiere, AP HP, Dept Anesthesia & Crit Care, F-75475 Paris, France. [Tolppanen, H.; Lassus, J.] Univ Helsinki, Cent Hosp, Heart & Lung Ctr, Helsinki, Finland. [Mueller, C.] Univ Basel Hosp, Dept Cardiol, CH-4031 Basel, Switzerland. [Mueller, C.] Univ Basel Hosp, Cardiovasc Res Inst Basel, CH-4031 Basel, Switzerland. [DiSomma, S.] Univ Roma La Sapienza, St Andrea Hosp, Dept Med Sci & Translat Med, Piazzale Aldo Moro 5, I-00185 Rome, Italy. [Baksyte, G.] Kaunas Univ Med, Dept Cardiol, Kaunas, Lithuania. [Cecconi, M.] St Georges Hosp & Med Sch, Anaesthesia & Intens Care, London SW17 0QT, England. [Choi, D. J.] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea. [Solal, A. Cohen] Hop Lariboisiere, AP HP, Dept Cardiol, F-75475 Paris, France. [Christ, M.] Paracelsus Med Univ, Dept Emergency & Intens Care Med, Nurnberg, Germany. [Masip, J.] Univ Barcelona, Consorci Sanitari Integral, Dept Intens Care Med, Barcelona, Spain. [Nouira, S.] Fattouma Bourguiba Univ Hosp, Emergency Dept, Monastir, Tunisia. [Nouira, S.] Fattouma Bourguiba Univ Hosp, Res Unit UR06SP21, Monastir, Tunisia. [Ojji, D.] Univ Abuja, Teaching Hosp, Dept Med, Cardiol Unit, Gwagwalada, Abuja, Nigeria. [Peacock, F.] Baylor Coll Med, Dept Emergency Med, Boston, MA USA. [Richards, M.] Christchurch Hosp, Christchurch Cardioendocrine Res Grp, Christchurch, New Zealand. [Sato, N.] Nippon Med Sch, Musashi Kosugi Hosp, Internal Med Cardiol & Intens Care Unit, Kawasaki, Kanagawa, Japan. [Sliwa, K.] Univ Cape Town, Hatter Inst Cardiovasc Res Africa, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. [Sliwa, K.] Univ Cape Town, IIDMM, ZA-7925 Cape Town, South Africa. [Spinar, J.] Univ Hosp Brno, Int Clin Res Ctr, Dept Cardiovasc Dis, Brno, Czech Republic. [Thiele, H.] Univ Hosp Schleswig Holstein, Univ Heart Ctr Luebeck, Med Clin Cardiol Angiol Intens Care Med 2, Lubeck, Germany. [Yilmaz, M. B.] Cumhuriyet Univ, Sch Med, Dept Cardiol, Sivas, Turkey. [Januzzi, J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mebazaa, A (reprint author), Hop Lariboisiere, AP HP, Dept Anesthesia & Crit Care, F-75475 Paris, France. EM alexandre.mebazaa@aphp.fr RI Cecconi, Maurizio/A-6241-2012; OI Cecconi, Maurizio/0000-0002-4376-6538; Nouira, Semir/0000-0002-0137-5491 FU Research Council of Lithuania [MIP-049/2015] FX The work of G. Baksyte was supported by the grant MIP-049/2015 from the Research Council of Lithuania. NR 94 TC 10 Z9 10 U1 2 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD FEB PY 2016 VL 42 IS 2 BP 147 EP 163 DI 10.1007/s00134-015-4041-5 PG 17 WC Critical Care Medicine SC General & Internal Medicine GA DB7UM UT WOS:000368722000002 PM 26370690 ER PT J AU Ehrmann, S Roche-Campo, F Bodet-Contentin, L Razazi, K Dugernier, J Trenado-Alvarez, J Donzeau, A Vermeulen, F Thevoz, D Papanikolaou, M Edelson, A Yoshido, HL Piquilloud, L Lakhal, K Lopes, C Vicent, C Desachy, A Apiou-Sbirlea, G Isabey, D Brochard, L AF Ehrmann, Stephan Roche-Campo, Ferran Bodet-Contentin, Laetitia Razazi, Keyvan Dugernier, Jonathan Trenado-Alvarez, Josep Donzeau, Alexis Vermeulen, Francois Thevoz, David Papanikolaou, Metaxia Edelson, Antoine Leon Yoshido, Hector Piquilloud, Lise Lakhal, Karim Lopes, Carlos Vicent, Carlos Desachy, Arnaud Apiou-Sbirlea, Gabriela Isabey, Daniel Brochard, Laurent CA Reva Res Network AT ICU Study Grp TI Aerosol therapy in intensive and intermediate care units: prospective observation of 2808 critically ill patients SO INTENSIVE CARE MEDICINE LA English DT Article DE Administration, inhalation [MeSH]; Metered dose inhalers [MeSH]; Nebulizers and vaporizers [MeSH]; Bronchodilator agents [MeSH]; Anti-bacterial agents [MeSH]; Respiration, artificial [MeSH] ID VENTILATOR-ASSOCIATED PNEUMONIA; RECEIVING MECHANICAL VENTILATION; CYSTIC-FIBROSIS; DELIVERY; NEBULIZATION; ANTIBIOTICS; INHALATION; EFFICIENCY; EVOLUTION; AMIKACIN AB Purpose: Unlike in the outpatient setting, delivery of aerosols to critically ill patients may be considered complex, particularly in ventilated patients, and benefits remain to be proven. Many factors influence aerosol delivery and recommendations exist, but little is known about knowledge translation into clinical practice. Method: Two-week cross-sectional study to assess the prevalence of aerosol therapy in 81 intensive and intermediate care units in 22 countries. All aerosols delivered to patients breathing spontaneously, ventilated invasively or noninvasively (NIV) were recorded, and drugs, devices, ventilator settings, circuit set-up, humidification and side effects were noted. Result: A total of 9714 aerosols were administered to 678 of the 2808 admitted patients (24 %, CI95 22-26 %), whereas only 271 patients (10 %) were taking inhaled medication before admission. There were large variations among centers, from 0 to 57 %. Among intubated patients 22 % (n = 262) received aerosols, and 50 % (n = 149) of patients undergoing NIV, predominantly (75 %) inbetween NIV sessions. Bronchodilators (n = 7960) and corticosteroids (n = 1233) were the most frequently delivered drugs (88 % overall), predominantly but not exclusively (49 %) administered to patients with chronic airway disease. An anti-infectious drug was aerosolized 509 times (5 % of all aerosols) for nosocomial infections. Jet-nebulizers were the most frequently used device (56 %), followed by metered dose inhalers (23 %). Only 106 (< 1 %) mild side effects were observed, despite frequent suboptimal set-ups such as an external gas supply of jet nebulizers for intubated patients. Conclusion:Aerosol therapy concerns every fourth critically ill patient and one-fifth of ventilated patients. C1 [Ehrmann, Stephan; Apiou-Sbirlea, Gabriela; Isabey, Daniel] Univ Paris Est, INSERM, UMR 955, Creteil, France. [Ehrmann, Stephan; Apiou-Sbirlea, Gabriela; Isabey, Daniel] Univ Paris Est, CNRS, ERL 7240, Equipe Biomecan Cellulaire & Resp, Creteil, France. [Ehrmann, Stephan; Bodet-Contentin, Laetitia] CHR Univ Tours, Reanimat Polyvalente, F-37044 Tours 9, France. [Ehrmann, Stephan] Univ Tours, Fac Med, INSERM, Ctr Etud Pathol Resp,UMR 1100,Aerosoltherapie & B, Tours, France. [Roche-Campo, Ferran] Hosp Verge Cinta, Med Intens, Tarragona, Spain. [Bodet-Contentin, Laetitia] Univ Paris 05, Sorbonne Paris Cite, Hop Cochin, AP HP,Reanimat Med, Paris, France. [Bodet-Contentin, Laetitia] Univ Paris 05, Sorbonne Paris Cite, Fac Med, Paris, France. [Razazi, Keyvan] GHU Henri Mondor, AP HP, DHU A TVB, Serv Reanimat Med,Grp Rech CARMAS, Creteil, France. [Dugernier, Jonathan] Clin Univ St Luc, Intens Care Unit, B-1200 Brussels, Belgium. [Trenado-Alvarez, Josep] Univ Barcelona, Hosp Univ Mutua Terrassa, Serv Med Intens, Barcelona, Spain. [Donzeau, Alexis; Piquilloud, Lise] Ctr Hosp Reg Univ Angers, Reanimat Med & Med Hyperbare, Angers, France. [Vermeulen, Francois] Hop Univ Geneve, Dept Intens Care, Rue Gabrielle Perret Gentil 4, CH-1211 Geneva, Switzerland. [Thevoz, David; Piquilloud, Lise] CHU Vaudois, Med Intens Adulte, CH-1011 Lausanne, Switzerland. [Thevoz, David; Piquilloud, Lise] CHU Vaudois, Ctr Brules, CH-1011 Lausanne, Switzerland. [Papanikolaou, Metaxia] Hippocrateion Gen Hosp Athens, Intens Care Unit, Athens, Greece. [Edelson, Antoine] Ctr Hosp Taaone, Reanimat, Pirae, Fr Polynesia. [Leon Yoshido, Hector] Hosp Nacl Edgardo Rebagliati Martins Essalud, Med Intens, Lima, Peru. [Lakhal, Karim] Ctr Hosp Reg Univ Nantes, Hop Laennec, Serv Anesthesie Reanimat, Reanimat Chirurg Polyvalente, F-44093 Nantes, France. [Lopes, Carlos] CHLN, Hosp Santa Maria, UCIR Pulmonol, Lisbon, Portugal. [Vicent, Carlos] Hosp Lluis Alcanyis, Intens Care Unit, Valencia, Spain. [Desachy, Arnaud] Ctr Hosp Angouleme, Serv Reanimat, Angouleme, France. [Apiou-Sbirlea, Gabriela] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Ctr Photomed, Boston, MA USA. [Brochard, Laurent] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, 30 Bond St, Toronto, ON M5B 1W8, Canada. [Brochard, Laurent] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. RP Ehrmann, S (reprint author), CHR Univ Tours, Reanimat Polyvalente, F-37044 Tours 9, France. EM stephanehrmann@gmail.com OI Curiel-Balsera, Emilio/0000-0002-9932-5053; Ehrmann, Stephan/0000-0001-6221-4467; Lopez-Herce, Jesus/0000-0001-6105-9178 FU Agence Nationale de la Recherche [ANR-2010 BLAN 1119 05] FX The authors acknowledge receipt of grant ANR-2010 BLAN 1119 05 from Agence Nationale de la Recherche. Beyond the investigators listed below, the authors sincerely thank all physicians, nursing and research staff who participated in the study. NR 36 TC 4 Z9 4 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD FEB PY 2016 VL 42 IS 2 BP 192 EP 201 DI 10.1007/s00134-015-4114-5 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA DB7UM UT WOS:000368722000006 PM 26602786 ER PT J AU Paul, S Song, PI Ogbechie, OA Sugai, DY Morley, KW Schalock, PC Kroshinsky, D AF Paul, Suchismita Song, Philip I. Ogbechie, Oluwatobi A. Sugai, Daniel Y. Morley, Keith W. Schalock, Peter C. Kroshinsky, Daniela TI Vesiculobullous and hemorrhagic erythema migrans: uncommon variants of a common disease SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID LYME-DISEASE; BORRELIOSIS AB BackgroundThe diagnosis of Lyme disease relies on the accurate diagnosis of erythema chronicum migrans (ECM) because serologic tests, culture, and polymerase chain reactions are often inaccurate. Although ECM is classically associated with a targetoid rash, there are many variants of this lesion. These variants of ECM are often initially diagnosed as cellulitis or spider bite reactions and treated with oral antibiotics. Inappropriate treatment further delays the diagnosis of Lyme disease, leading to late complications. MethodsWe present four cases of vesiculobullous and hemorrhagic ECM, a less common variant of ECM. ResultsAll four patients had a history of exposure to wooded areas in Massachusetts during the summer months. In these patients, ECM presented with central vesicles and bullae with hemorrhage, crusting, and in some cases necrosis. Serologic testing was positive in three of the four cases at presentation. In one case, microscopic examination of a skin biopsy showed epidermal spongiosis with parakeratosis, focal necrosis, papillary dermal edema, erythrocyte extravasation, and a superficial and deep perivascular lymphocytic infiltrate with neutrophils and eosinophils of the dermis. No fungal organisms or bacteria were identified. All four patients were treated with doxycycline with complete resolution of symptoms. ConclusionsIt is important to recognize the vesiculobullous and hemorrhagic variants of ECM in order to minimize the provision of inappropriate antibiotic treatment for other diagnoses. Early diagnosis of ECM and the initiation of appropriate antibiotics may prevent late complications of Lyme disease. C1 [Paul, Suchismita; Ogbechie, Oluwatobi A.; Schalock, Peter C.; Kroshinsky, Daniela] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Song, Philip I.; Sugai, Daniel Y.; Morley, Keith W.; Schalock, Peter C.; Kroshinsky, Daniela] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schalock, PC (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,BAR622, Boston, MA 02114 USA. EM schalock.prof@gmail.com NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0011-9059 EI 1365-4632 J9 INT J DERMATOL JI Int. J. Dermatol. PD FEB PY 2016 VL 55 IS 2 BP E79 EP E82 DI 10.1111/ijd.12927 PG 4 WC Dermatology SC Dermatology GA DC0XW UT WOS:000368942300005 PM 26498075 ER PT J AU Solus, JF Murphy, GF Kraft, S AF Solus, Jason F. Murphy, George F. Kraft, Stefan TI Cutaneous Squamous Cell Carcinomas of the Lower Extremities Show Distinct Clinical and Pathologic Features SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE squamous cell carcinoma; actinic keratosis; skin neoplasms; stem cells ID NONMELANOMA SKIN-CANCER; ACTINIC KERATOSIS; STEM-CELLS; RECOGNIZED NEOPLASM; NOTCH-1 EXPRESSION; CYTOKERATIN 15; P53 MUTATIONS; UNITED-STATES; LESIONS; HEAD AB Cutaneous squamous cell carcinomas mainly affect older, predominantly male patients. Most are due to chronic ultraviolet exposure, and associated with actinic keratoses. On the lower extremities, they occur more commonly in women. However, data on these tumors as a distinct group are scarce. We evaluated 61 squamous cell carcinomas of the lower extremities. Overall, 69% of patients were female. Mean age was 75 years. More than 90% of tumors were well differentiated, 3% showed perineural invasion, and none lymphovascular invasion. In all, 63.9% showed evidence of severe chronic sun damage. Associated actinic keratoses were identified in only 13% of cases. By contrast, 80% were associated with distinctive basal epidermal proliferations with a retiform growth pattern. These proliferations were evaluated immunohistochemically for keratinocyte stem cell markers, p53 and Notch1 in 15 cases. All cases were positive for cytokeratin 14, p53, and Notch1 (with variable intensity in the latter 2), and predominantly negative for cytokeratin 19. Interestingly, basal retiform proliferations were positive for cytokeratin 15 in 66% of cases. Fifteen head and neck squamous cell carcinomas were evaluated in comparison. Those lacked associated basal retiform proliferations except in 1 case. In contrast, 87% were associated with actinic keratoses and 100% with severe chronic sun damage. Actinic keratoses associated with head and neck tumors showed cytokeratin 15 staining only in 7% of cases (P = .003 compared with cytokeratin 15 in basal retiform proliferations associated with leg carcinomas). These findings support the hypothesis that lower extremity squamous cell carcinomas are distinct and may exhibit a pathogenesis less reliant on actinic damage. C1 [Solus, Jason F.; Kraft, Stefan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Solus, Jason F.] Washington Univ, Sch Med, St Louis, MO USA. [Murphy, George F.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Kraft, S (reprint author), Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St, Boston, MA 02114 USA. EM skraft@mgh.harvard.edu NR 38 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 EI 1940-2465 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD FEB PY 2016 VL 24 IS 1 BP 29 EP 36 DI 10.1177/1066896915599058 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA DC0VU UT WOS:000368936800004 PM 26261102 ER PT J AU Knapp, AA Blumenthal, H Mischel, ER Badour, CL Leen-Feldner, EW AF Knapp, Ashley A. Blumenthal, Heidemarie Mischel, Emily R. Badour, Christal L. Leen-Feldner, Ellen W. TI Anxiety Sensitivity and Its Factors in Relation to Generalized Anxiety Disorder among Adolescents SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Anxiety sensitivity; Worry; Generalized anxiety disorder; Adolescents ID REVISED CHILD ANXIETY; DSM-IV ANXIETY; EMOTIONAL DISORDERS; DEPRESSION SCALE; UNIFIED PROTOCOL; NEGATIVE AFFECT; PANIC-ATTACKS; SYMPTOMS; INDEX; WORRY AB Anxiety psychopathology, one of the most prevalent classes of disorder among youth, is linked to detrimental outcomes. Accordingly, identifying factors that influence vulnerability to anxiety disorders is important. One promising factor, given emerging evidence for its transdiagnostic nature, is anxiety sensitivity (AS); however, relatively little is known about the linkage between AS and indicators of generalized anxiety disorder (GAD), particularly among youth. The aim of the current investigation was to address this gap in the literature using a community-based sample of adolescents aged 10-17 years (n = 165; M (age) = 14.49 years, SD = 2.26). Results indicated global AS and the AS-physical concerns dimension were significantly associated with worry, generalized anxiety symptoms, and GAD diagnosis assessed via a structured clinical interview, above and beyond key theoretically-relevant covariates. These findings add to a growing body of work underscoring the relevance of AS for multiple types of anxiety-related disorders among youth. C1 [Knapp, Ashley A.; Mischel, Emily R.; Leen-Feldner, Ellen W.] Univ Arkansas, Dept Psychol Sci, 216 Mem Hall, Fayetteville, AR 72701 USA. [Blumenthal, Heidemarie] Univ N Texas, Dept Psychol, 155 Union Circle 311280, Denton, TX 76203 USA. [Badour, Christal L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,MSC 861,2nd Fl IOP South Bldg, Charleston, SC 29425 USA. [Badour, Christal L.] Ralph H Johnson VA Med Ctr, Dept Psychiat, 109 Bee St, Charleston, SC 29401 USA. RP Knapp, AA (reprint author), Univ Arkansas, Dept Psychol Sci, 216 Mem Hall, Fayetteville, AR 72701 USA. EM aaknapp@uark.edu NR 70 TC 2 Z9 2 U1 6 U2 17 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 EI 1573-2835 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD FEB PY 2016 VL 44 IS 2 BP 233 EP 244 DI 10.1007/s10802-015-9991-0 PG 12 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA DC1ZF UT WOS:000369016300003 PM 25724327 ER PT J AU Walter, ND Miller, MA Vasquez, J Weiner, M Chapman, A Engle, M Higgins, M Quinones, AM Rosselli, V Canono, E Yoon, C Cattamanchi, A Davis, JL Phang, T Stearman, RS Datta, G Garcia, BJ Daley, CL Strong, M Kechris, K Fingerlin, TE Reves, R Geraci, MW AF Walter, Nicholas D. Miller, Mikaela A. Vasquez, Joshua Weiner, Marc Chapman, Adam Engle, Melissa Higgins, Michael Quinones, Amy M. Rosselli, Vanessa Canono, Elizabeth Yoon, Christina Cattamanchi, Adithya Davis, J. Lucian Phang, Tzu Stearman, Robert S. Datta, Gargi Garcia, Benjamin J. Daley, Charles L. Strong, Michael Kechris, Katerina Fingerlin, Tasha E. Reves, Randall Geraci, Mark W. TI Blood Transcriptional Biomarkers for Active Tuberculosis among Patients in the United States: a Case-Control Study with Systematic Cross-Classifier Evaluation SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SIGNATURES; EXPRESSION; MEDICINE; AFRICA AB Blood transcriptional signatures are promising for tuberculosis (TB) diagnosis but have not been evaluated among U.S. patients. To be used clinically, transcriptional classifiers need reproducible accuracy in diverse populations that vary in genetic composition, disease spectrum and severity, and comorbidities. In a prospective case-control study, we identified novel transcriptional classifiers for active TB among U.S. patients and systematically compared their accuracy to classifiers from published studies. Blood samples from HIV-uninfected U.S. adults with active TB, pneumonia, or latent TB infection underwent whole-transcriptome microarray. We used support vector machines to classify disease state based on transcriptional patterns. We externally validated our classifiers using data from sub-Saharan African cohorts and evaluated previously published transcriptional classifiers in our population. Our classifier distinguishing active TB from pneumonia had an area under the concentration-time curve (AUC) of 96.5% (95.4% to 97.6%) among U.S. patients, but the AUC was lower (90.6% [89.6% to 91.7%]) in HIV-uninfected Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 90.0% (87.7% to 92.3%) and 82.9% (80.8% to 85.1%) when tested in U.S. patients. Our classifier distinguishing active TB from latent TB had AUC values of 95.9% (95.2% to 96.6%) among U.S. patients and 95.3% (94.7% to 96.0%) among Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 98.0% (97.4% to 98.7%) and 94.8% (92.9% to 96.8%) when tested in U.S. patients. Blood transcriptional classifiers accurately detected active TB among U.S. adults. The accuracy of classifiers for active TB versus that of other diseases decreased when tested in new populations with different disease controls, suggesting additional studies are required to enhance generalizability. Classifiers that distinguish active TB from latent TB are accurate and generalizable across populations and can be explored as screening assays. C1 [Walter, Nicholas D.] Vet Adm Med Ctr, Pulm Sect, Denver, CO 80220 USA. [Walter, Nicholas D.; Chapman, Adam; Phang, Tzu; Stearman, Robert S.; Geraci, Mark W.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Walter, Nicholas D.; Miller, Mikaela A.; Rosselli, Vanessa; Kechris, Katerina; Fingerlin, Tasha E.; Reves, Randall] Univ Colorado Denver, Colorado Sch Publ Hlth, Aurora, CO USA. [Vasquez, Joshua; Yoon, Christina; Cattamanchi, Adithya; Davis, J. Lucian] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Weiner, Marc; Engle, Melissa] Vet Adm Med Ctr, Dept Med, San Antonio, TX USA. [Higgins, Michael; Reves, Randall] Denver Metro TB Control Program, Denver, CO USA. [Quinones, Amy M.] Denver Hlth Med Ctr, Denver, CO USA. [Canono, Elizabeth] Natl Jewish Hlth, Clin Translat Res Ctr, Denver, CO USA. [Datta, Gargi; Garcia, Benjamin J.; Strong, Michael] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA. [Daley, Charles L.] Natl Jewish Hlth, Div Mycobacterial & Resp Infect, Denver, CO USA. [Davis, J. Lucian] Yale Univ, Sch Publ Hlth, Epidemiol Microbial Dis, New Haven, CT USA. [Stearman, Robert S.] Indiana Univ, Dept Med, Indianapolis, IN USA. [Fingerlin, Tasha E.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA. [Geraci, Mark W.] Indiana Univ, Dept Med, Indianapolis, IN USA. RP Walter, ND (reprint author), Vet Adm Med Ctr, Pulm Sect, Denver, CO 80220 USA.; Walter, ND (reprint author), Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO USA.; Walter, ND (reprint author), Univ Colorado Denver, Colorado Sch Publ Hlth, Aurora, CO USA. EM nicholas.walter@ucdenver.edu OI Garcia, Benjamin/0000-0001-5524-6946 FU Veteran's Administration Career Development Award Colorado Clinical and Translational Sciences Institute, Mucosal and Vaccine Research Colorado [CDA 1IK2CX000914-01A1]; University of Colorado Denver Division of Pulmonary Sciences and Critical Care Medicine FX The Veteran's Administration Career Development Award (CDA 1IK2CX000914-01A1) Colorado Clinical and Translational Sciences Institute, Mucosal and Vaccine Research Colorado and the University of Colorado Denver Division of Pulmonary Sciences and Critical Care Medicine provided funding. NR 24 TC 2 Z9 2 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 2016 VL 54 IS 2 BP 274 EP 282 DI 10.1128/JCM.01990-15 PG 9 WC Microbiology SC Microbiology GA DC3YD UT WOS:000369155100006 PM 26582831 ER PT J AU Zhang, Y Jenkins, AJ Basu, A Stoner, JA Lopes-Virella, MF Klein, RL Lyons, TJ AF Zhang, Ying Jenkins, Alicia J. Basu, Arpita Stoner, Julie A. Lopes-Virella, Maria F. Klein, Richard L. Lyons, Timothy J. CA DCCT EDIC Res Grp TI Associations between intensive diabetes therapy and NMR-determined lipoprotein subclass profiles in type 1 diabetes SO JOURNAL OF LIPID RESEARCH LA English DT Article DE intensive diabetes treatment; dyslipidemia; atherosclerosis; clinical trial; high density lipoprotein; low density lipoprotein; nuclear magnetic resonance ID MAGNETIC-RESONANCE-SPECTROSCOPY; CORONARY-ARTERY-DISEASE; INTIMA-MEDIA THICKNESS; COMPLICATIONS TRIAL; HEART-DISEASE; CARDIOVASCULAR-DISEASE; DCCT/EDIC COHORT; FOLLOW-UP; CAROTID ATHEROSCLEROSIS; PARTICLE CONCENTRATIONS AB Our objective is to define differences in circulating lipoprotein subclasses between intensive versus conventional management of type 1 diabetes during the randomization phase of the Diabetes Control and Complications Trial (DCCT). NMR-determined lipoprotein subclass profiles (NMR-LSPs), which estimate molar subclass concentrations and mean particle diameters, were determined in 1,294 DCCT subjects after a median of 5 years (interquartile range: 4-6 years) of randomization to intensive or conventional diabetes management. In cross-sectional analyses, we compared standard lipids and NMR-LSPs between treatment groups. Standard total, LDL, and HDL cholesterol levels were similar between randomization groups, while triglyceride levels were lower in the intensively treated group. NMR-LSPs showed that intensive therapy was associated with larger LDL diameter (20.7 vs. 20.6 nm, P = 0.01) and lower levels of small LDL (median: 465 vs. 552 nmol/l, P = 0.007), total IDL/LDL (mean: 1,000 vs. 1,053 nmol/l, P = 0.01), and small HDL (mean: 17.3 vs. 18.6 mu mol/l, P < 0.0001), the latter accounting for reduced total HDL (mean: 33.8 vs. 34.8 mu mol/l, P = 0.01). In conclusion, intensive diabetes therapy was associated with potentially favorable changes in LDL and HDL subclasses in sera. Further research will determine whether these changes contribute to the beneficial effects of intensive diabetes management on vascular complications. C1 [Zhang, Ying; Stoner, Julie A.] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK USA. [Lyons, Timothy J.] Univ Oklahoma, Hlth Sci Ctr, Sect Endocrinol & Diabet, Oklahoma City, OK USA. [Jenkins, Alicia J.] Univ Sydney, Natl Hlth & Med Res Council, Clin Trials Ctr, Sydney, NSW 2006, Australia. [Jenkins, Alicia J.; Lyons, Timothy J.] Queens Univ Belfast, Ctr Med Expt, Belfast BT7 1NN, Antrim, North Ireland. [Basu, Arpita] Oklahoma State Univ, Dept Nutr Sci, Stillwater, OK 74078 USA. [Lopes-Virella, Maria F.; Klein, Richard L.] Med Univ S Carolina, Div Endocrinol, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.; Klein, Richard L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Lyons, TJ (reprint author), Univ Oklahoma, Hlth Sci Ctr, Sect Endocrinol & Diabet, Oklahoma City, OK USA.; Lyons, TJ (reprint author), Queens Univ Belfast, Ctr Med Expt, Belfast BT7 1NN, Antrim, North Ireland. EM t.lyons@qub.ac.uk FU National Institutes of Health [R01DK080043]; American Diabetes Association [7-12-CT-46]; Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases; National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program; National Eye Institute, the National Institute of Neurologic Disorders and Stroke, Clinical Translational Science Center Program FX This project was supported by grants from the National Institutes of Health (R01DK080043) and the American Diabetes Association (7-12-CT-46). DCCT/EDIC has been supported by U01 Cooperative Agreement grants (1982-1993, 2011-2016) and contracts (1982-2011) from the Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present). The authors have no relevant conflicts of interest to disclose. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 52 TC 2 Z9 2 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 2016 VL 57 IS 2 BP 310 EP 317 DI 10.1194/jlr.P060657 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DC3AN UT WOS:000369091600014 PM 26658239 ER PT J AU Jeong, SY Jeon, R Choi, YK Jung, JE Liang, A Xing, CH Wang, XY Lo, EH Song, YS AF Jeong, Si-Yeon Jeon, Raok Choi, Yoon Kyung Jung, Joo Eun Liang, Anna Xing, Changhong Wang, Xiaoying Lo, Eng H. Song, Yun Seon TI Activation of microglial Toll-like receptor 3 promotes neuronal survival against cerebral ischemia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cerebral ischemia; interleukin-6; microglia; neuroprotection; oxygen glucose deprivation; Toll-like receptor 3 ID HUMAN ASTROCYTES; IN-VITRO; INJURY; EXPRESSION; BRAIN; PHAGOCYTOSIS; MECHANISMS; PROTECTS; ACID AB Emerging experimental evidence suggests that activation of Toll-like receptor 3 (TLR3) by its agonist polyinosinic polycytidylic acid (poly-ICLC) protects neurons against cerebral ischemia, but the underlying mechanisms remain largely unknown. In the brain, TLR3 is mostly expressed in glial cells. Therefore, we assess the hypothesis that TLR3 activation in microglia is required for neuroprotection against ischemia. After transient focal cerebral ischemia, microglia/macrophages (MMs) demonstrate a significant reduction in TLR3 and its downstream cytokine interleukin 6 (IL-6). Subsequently, activation of TLR3 by poly-ICLC restored TLR3 expression and decreased infarction. To further investigate these mechanisms, we turned to a primary cell culture system. Consistent with the invivo findings, oxygen-glucose deprivation (OGD) significantly reduced TLR3 and IL-6 mRNA expression in microglia, but poly-ICLC significantly rescued TLR3 and IL-6 expression. Importantly, conditioned media from OGD-treated microglia increased neuronal death after OGD. In contrast, the conditioned media from microglia treated with poly-ICLC after OGD significantly protected against OGD-induced neuron death. Taken together, our findings provide proof-of-concept that activation of TLR3 in microglia may promote neuron survival after ischemia. C1 [Jeong, Si-Yeon; Jeon, Raok; Song, Yun Seon] Sookmyung Womens Univ, Coll Pharm, Seoul, South Korea. [Choi, Yoon Kyung; Jung, Joo Eun; Liang, Anna; Xing, Changhong; Wang, Xiaoying; Lo, Eng H.; Song, Yun Seon] Harvard Univ, Neuroprotect Res Lab, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. [Choi, Yoon Kyung; Jung, Joo Eun; Liang, Anna; Xing, Changhong; Wang, Xiaoying; Lo, Eng H.; Song, Yun Seon] Harvard Univ, Neuroprotect Res Lab, Dept Neurol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. RP Lo, EH; Song, YS (reprint author), Harvard Univ, Neuroprotect Res Lab, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA.; Lo, EH; Song, YS (reprint author), Harvard Univ, Neuroprotect Res Lab, Dept Neurol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. EM lo@helix.mgh.edu; yssong@sookmyung.ac.kr FU National Research Foundation of Korea [2010-00894]; Medical Research Center Program through the National Research Foundation of Korea (NRF) - Korea Government (MSIP) [2011-0030074] FX The authors declare no conflict of interest. This work was supported by the National Research Foundation of Korea (grant # 2010-00894) and the Medical Research Center Program (No. 2011-0030074) through the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) to Y.S.S. NR 18 TC 1 Z9 1 U1 3 U2 8 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 FEB PY 2016 VL 136 IS 4 BP 851 EP 858 DI 10.1111/jnc.13441 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DC3UU UT WOS:000369145200017 ER PT J AU Ramachandran, M Retarekar, R Raghavan, ML Berkowitz, B Dickerhoff, B Correa, T Lin, S Johnson, K Hasan, D Ogilvy, C Rosenwasser, R Torner, J Bogason, E Stapleton, CJ Harbaugh, RE AF Ramachandran, Manasi Retarekar, Rohini Raghavan, Madhavan L. Berkowitz, Benjamin Dickerhoff, Benjamin Correa, Tatiana Lin, Steve Johnson, Kevin Hasan, David Ogilvy, Christopher Rosenwasser, Robert Torner, James Bogason, Einar Stapleton, Christopher J. Harbaugh, Robert E. TI Assessment of image-derived risk factors for natural course of unruptured cerebral aneurysms SO JOURNAL OF NEUROSURGERY LA English DT Article DE aneurysm; quantified aneurysm shape; subarachnoid hemorrhage; aneurysm growth; vascular disorders ID WALL SHEAR-STRESS; INTRACRANIAL ANEURYSMS; RUPTURE RISK; CT ANGIOGRAPHY; HEMODYNAMICS; RECONSTRUCTION; HISTORY; ARTERY; SHAPE; SIZE AB OBJECTIVE The goal of this prospective longitudinal study was to test whether image-derived metrics can differentiate unruptured aneurysms that will become unstable (grow and/or rupture) from those that will remain stable. METHODS One hundred seventy-eight patients harboring 198 unruptured cerebral aneurysms for whom clinical observation and follow-up with imaging surveillance was recommended at 4 clinical centers were prospectively recruited into this study. Imaging data (predominantly CT angiography) at initial presentation was recorded. Computational geometry was used to estimate numerous metrics of aneurysm morphology that described the size and shape of the aneurysm. The nonlinear, finite element method was used to estimate uniform pressure-induced peak wall tension. Computational fluid dynamics was used to estimate blood flow metrics. The median follow-up period was 645 days. Longitudinal outcome data on these aneurysm patients-whether their aneurysms grew or ruptured (the unstable group) or remained unchanged (the stable group)-was documented based on follow-up at 4 years after the beginning of recruitment. RESULTS Twenty aneurysms (10.1%) grew, but none ruptured. One hundred forty-nine aneurysms (75.3%) remained stable and 29 (14.6%) were lost to follow-up. None of the metrics-including aneurysm size, nonsphericity index, peak wall tension, and low shear stress area-differentiated the stable from unstable groups with statistical significance. CONCLUSIONS The findings in this highly selected group do not support the hypothesis that image-derived metrics can predict aneurysm growth in patients who have been selected for observation and imaging surveillance. If aneurysm shape is a significant determinant of invasive versus expectant management, selection bias is a key limitation of this study. C1 [Ramachandran, Manasi; Retarekar, Rohini; Raghavan, Madhavan L.; Berkowitz, Benjamin; Dickerhoff, Benjamin; Correa, Tatiana; Lin, Steve] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA. [Johnson, Kevin; Hasan, David] Univ Iowa Hosp & Clin, Dept Neurosurg, Iowa City, IA 52242 USA. [Torner, James] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Ogilvy, Christopher] Beth Israel Deaconess Med Ctr, Dept Surg, Div Neurosurg, 330 Brookline Ave, Boston, MA 02215 USA. [Stapleton, Christopher J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Rosenwasser, Robert] Jefferson Univ Hosp, Dept Neurosurg, Philadelphia, PA USA. [Bogason, Einar; Harbaugh, Robert E.] Penn State Univ, Dept Neurosurg, Hershey, PA USA. [Harbaugh, Robert E.] Penn State Univ, Dept Engn Sci & Mech, State Coll, PA USA. RP Harbaugh, RE (reprint author), Penn State Milton S Hershey Med Ctr, Dept Neurosurg, 30 Hope Dr, Hershey, PA 17033 USA. EM reh1@mac.com FU National Heart Lung and Blood Institute [R01HL083475] FX This study was funded by National Heart Lung and Blood Institute grant no. R01HL083475, "Assessment of intracranial aneurysm shape as an indicator of rupture risk." The work described in this manuscript is based on Ph.D. dissertations by the co-lead authors, Ramachandran24 and Retarekar.27 We are grateful to Deborah Hoffman, study clinical coordinator at Penn State Milton S. Hershey Medical Center, for collection and organization of clinical data. We are grateful to the Vascular Modeling ToolKit (VMTK) developer and user community for assistance with image processing. NR 37 TC 2 Z9 2 U1 1 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2016 VL 124 IS 2 BP 288 EP 295 DI 10.3171/2015.2.JNS142265 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DB9VR UT WOS:000368866300003 PM 26381246 ER PT J AU Barker, FG AF Barker, Fred G., II TI Randomized clinical trials and neurosurgery SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID GLIOBLASTOMA-MULTIFORME; PARKINSONS-DISEASE; RADIATION-THERAPY; CNS 2007; SURVIVAL; SURGERY; QUALITY; INTERVENTION; ADHERENCE; JOURNALS C1 [Barker, Fred G., II] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 56 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2016 VL 124 IS 2 BP 552 EP 556 DI 10.3171/2015.2.JNS142960 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DB9VR UT WOS:000368866300039 PM 26315008 ER PT J AU Kepler, CK Vaccaro, AR Chen, E Patel, AA Ahn, H Nassr, A Shaffrey, CI Harrop, J Schroeder, GD Agarwala, A Dvorak, MF Fourney, DR Wood, KB Traynelis, VC Yoon, ST Fehlings, MG Aarabi, B AF Kepler, Christopher K. Vaccaro, Alexander R. Chen, Eric Patel, Alpesh A. Ahn, Henry Nassr, Ahmad Shaffrey, Christopher I. Harrop, James Schroeder, Gregory D. Agarwala, Amit Dvorak, Marcel F. Fourney, Daryl R. Wood, Kirkham B. Traynelis, Vincent C. Yoon, S. Tim Fehlings, Michael G. Aarabi, Bizhan TI Treatment of isolated cervical facet fractures: a systematic review SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Review DE systematic reviews; unilateral facet fracture; bilateral facet fracture; surgical reduction; closed reduction; cervical; trauma ID ANTERIOR FUSION; SPINE; DISLOCATIONS; SUBLUXATION; PATTERNS; INJURY AB OBJECTIVE In this clinically based systematic review of cervical facet fractures, the authors' aim was to determine the optimal clinical care for patients with isolated fractures of the cervical facets through a systematic review. METHODS A systematic review of nonoperative and operative treatment methods of cervical facet fractures was performed. Reduction and stabilization treatments were compared, and analysis of postoperative outcomes was performed. MEDLINE and Scopus databases were used. This work was supported through support received from the Association for Collaborative Spine Research and AOSpine North America. RESULTS Eleven studies with 368 patients met the inclusion criteria. Forty-six patients had bilateral isolated cervical facet fractures and 322 had unilateral isolated cervical facet fractures. Closed reduction was successful in 56.4% (39 patients) and 63.8% (94 patients) of patients using a halo vest and Gardner-Wells tongs, respectively. Comparatively, open reduction was successful in 94.9% of patients (successful reduction of open to closed reduction OR 12.8 [95% CI 6.1-26.9], p < 0.0001); 183 patients underwent internal fixation, with an 87.2% success rate in maintaining anatomical alignment. When comparing the success of patients who underwent anterior versus posterior procedures, anterior approaches showed a 90.5% rate of maintenance of reduction, compared with a 75.6% rate for the posterior approach (anterior vs posterior OR 3.1 [95% CI 1.0-9.4], p = 0.05). CONCLUSIONS In comparison with nonoperative treatments, operative treatments provided a more successful outcome in terms of failure of treatment to maintain reduction for patients with cervical facet fractures. Operative treatment appears to provide superior results to the nonoperative treatments assessed. C1 [Kepler, Christopher K.; Vaccaro, Alexander R.; Schroeder, Gregory D.] Rothman Inst, Dept Orthopaed Surg, Philadelphia, PA USA. [Kepler, Christopher K.; Vaccaro, Alexander R.; Schroeder, Gregory D.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Chen, Eric; Harrop, James] Thomas Jefferson Univ Hosp, Dept Neurosurg, Philadelphia, PA 19107 USA. [Patel, Alpesh A.] NW Mem Hosp, Dept Orthopaed Surg, Chicago, IL 60611 USA. [Ahn, Henry] Univ Toronto, Dept Orthopaed Surg, Toronto, ON M5S 1A1, Canada. [Fehlings, Michael G.] Univ Toronto, Dept Neurosurg, Toronto, ON M5S 1A1, Canada. [Nassr, Ahmad] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. [Shaffrey, Christopher I.] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA. [Agarwala, Amit] Panorama Orthoped & Spine Ctr, Denver, CO USA. [Dvorak, Marcel F.] Univ British Columbia, Dept Orthopaed Surg, Vancouver, BC V5Z 1M9, Canada. [Fourney, Daryl R.] Univ Saskatchewan, Dept Neurosurg, Saskatoon, SK, Canada. [Wood, Kirkham B.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Traynelis, Vincent C.] Rush Univ, Med Ctr, Dept Neurosurg, Chicago, IL 60612 USA. [Yoon, S. Tim] Emory Univ, Dept Orthopaed Surg, Atlanta, GA 30322 USA. [Aarabi, Bizhan] Univ Maryland, Dept Neurosurg, Baltimore, MD 21201 USA. RP Schroeder, GD (reprint author), 925 Chesnut St,5th Fl, Philadelphia, PA 19107 USA. EM gregdschroeder@gmail.com FU Medtronic; Springer; AOSpine; CSRS; OREF; NACTN; NIH; Department of Defense; AO; NREF; UVa; Asubio Pharmaceuticals; Canadian Institute of Health Research; Rick Hansen Foundation; Saskatchewan Health Research Foundation; Royal University Hospital; Globus Medical; K2M; Synthes; Globus FX The authors report that AOSpine and the Association for Collaborative Spine Research provided resources to help with this paper. The authors report the following. Dr Schroeder: funding from Medtronic for travel to meetings. Dr. Kepler: consultant for Healthgrades. Dr. Vaccaro: consultant for Medtronic, Stryker Spine, Globus, Stout Medical, Gerson Lehrman Group, Guidepoint Global, Medacorp, Innovative Surgical Design, and Orthobullets; expert testimony for Ellipse; service on scientific advisory board/board of directors/service on committees for innovative surgical design for Spinicity, AOSpine, and Association of Collaborative Spine Research; royalties from Thieme, Jaypee, Elsevier, Taylor Francis, Aesculap, Globus, Medtronic, Stryker, and Biomet Spine; institutional support from Cerapedics; owns stock in Spine Medica, Computational Biodynamics, Progressive Spinal Technologies, Spinology, Small Bone Innovations, Cross Current, In Vivo, Flagship Surgical, Advanced Spinal Intellectual Properties, Cytonics, Bonovo Orthopaedics, Electrocore, Gamma Spine, Location Based Intelligence, FlowPharma, R.S.I., Replication Medica, Globus, Stout Medical, Rothman Institute and Related Properties, Innovative Surgical Design, Spinicity; and Paradigm Spine. Dr. Patel: consultant for Biomet, DePuy (A Johnson & Johnson Company), Stryker, Zimmer, GE Healthcare Nocimed, Amedica, Ulrich, and Relievant; direct stock ownership in Amedica, Trinity Orthopaedics, Cytonics, Nocimed, and Vital 5; IP royalties from Amedica and Ulrich Medical USA; publishing royalties, financial or material support from Springer; board or committee member AAOS, American College of Surgeons, American Orthopaedic Association, AOSpine North America, Cervical Spine Research Society, Indo-American Spine Alliance, Lumbar Spine Research Society, and North American Spine Society; and editorial or governing board of Journal of the American Academy of Orthopaedic Surgeons, Surgical Neurology International, and Wolters Kluwer Health Lippincott Williams & Wilkins. Dr. Nassr: grants from AOSpine, CSRS, and OREF; and fellowship support from AOSpine. Dr. Harrop: consultant for DePuy and Bioventus; grants from NACTN; and fellowship Support from AOSpine NA. Dr. Shaffrey: consultant for Biomet, Globus, Medtronic, NuVasive, and Stryker; stock ownership in NuVasive; patent holder with Biomet, Medtronic, and NuVasive; royalties from Biomet and Medtronic; grants from NIH, Department of Defense, AO, NREF, and NACTN; fellowship support: NREF, AO, and UVa; non study-related support form ISSG and DePuy Synthes. Dr. Agarawala: consultant for Medtronic. Dr. Fourney: research support from Asubio Pharmaceuticals; grants from Canadian Institute of Health Research, Rick Hansen Foundation, Saskatchewan Health Research Foundation, Royal University Hospital, and AOSpine, and fellowship support from AOSpine. Dr. Wood: stock ownership in TranS1; other financial or material support from Globus Medical and OREF; research support from K2M; editorial or governing board of Spine and Spinal Deformity; and fellowship support form Synthes. Dr. Traynelis: consultant for, royalties from, patent holder with, and research support from Medtronic; grants from NIH; and fellowship support from Globus. Dr.; Yoon: consultant for Meditech Advisors, and Stryker; and intellectual property royalties from Stryker and Meditech; stock ownership in Alphatec Spine, Meditech Advisors, Medyssey, and Phygen; editorial or governing board for American Journal of Orthopedics, Journal of Bone and Joint Surgery American, Journal of Orthopaedic Research, The Spine Journal, Spine; and board or committee member of International Society for the Study of the Lumbar Spine. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 EI 1547-5646 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD FEB PY 2016 VL 24 IS 2 BP 347 EP 354 DI 10.3171/2015.6.SPINE141260 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DB9VO UT WOS:000368866000022 ER PT J AU Karnezis, AN Wang, YM Ramos, P Hendricks, WPD Oliva, E D'Angelo, E Prat, J Nucci, MR Nielsen, TO Chow, C Leung, S Kommoss, F Kommoss, S Silva, A Ronnett, BM Rabban, JT Bowtell, DD Weissman, BE Trent, JM Gilks, CB Huntsman, DG AF Karnezis, Anthony N. Wang, Yemin Ramos, Pilar Hendricks, William P. D. Oliva, Esther D'Angelo, Emanuela Prat, Jaime Nucci, Marisa R. Nielsen, Torsten O. Chow, Christine Leung, Samuel Kommoss, Friedrich Kommoss, Stefan Silva, Annacarolina Ronnett, Brigitte M. Rabban, Joseph T. Bowtell, David D. Weissman, Bernard E. Trent, Jeffrey M. Gilks, C. Blake Huntsman, David G. TI Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type SO JOURNAL OF PATHOLOGY LA English DT Article DE small cell carcinoma; hypercalcaemic type; rhabdoid tumour; SMARCA4/BRG1; SMARCA2/BRM; SMARCB1/INI1; SWI/SNF; HDAC inhibitor; trichostatin A; epigenetic silencing ID NEUROENDOCRINE CARCINOMA; CANCER GENOMICS; CD44 EXPRESSION; DOWN-REGULATION; BRM EXPRESSION; RHABDOID TUMOR; CYCLE ARREST; LUNG-CANCER; HIGH-GRADE; BRG-1 AB Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) is a lethal and sometimes familial ovarian tumour of young women and children. We and others recently discovered that over 90% of SCCOHTs harbour inactivating mutations in the chromatin remodelling gene SMARCA4 with concomitant loss of its encoded protein SMARCA4 (BRG1), one of two mutually exclusive ATPases of the SWI/SNF chromatin remodelling complex. To determine the specificity of SMARCA4 loss for SCCOHT, we examined the expression of SMARCA4 by immunohistochemistry in more than 3000 primary gynaecological tumours. Among ovarian tumours, it was only absent in clear cell carcinoma (15 of 360, 4%). In the uterus, it was absent in endometrial stromal sarcomas (4 of 52, 8%) and high-grade endometrioid carcinomas (2 of 338, 1%). Recent studies have shown that SMARCA2 (BRM), the other mutually exclusive ATPase of the SWI/SNF complex, is necessary for survival of tumour cells lacking SMARCA4. Therefore, we examined SMARCA2 expression and discovered that all SMARCA4-negative SCCOHTs also lacked SMARCA2 protein by IHC, including the SCCOHT cell lines BIN67 and SCCOHT1. Among ovarian tumours, the SMARCA4/SMARCA2 dual loss phenotype appears completely specific for SCCOHT. SMARCA2 loss was not due to mutation but rather from an absence of mRNA expression, which was restored by treatment with the histone deacetylase inhibitor trichostatin A. Re-expression of SMARCA4 or SMARCA2 inhibited the growth of BIN67 and SCCOHT1 cell lines. Our results indicate that SMARCA4 loss, either alone or with SMARCA2, is highly sensitive and specific for SCCOHT and that restoration of either SWI/SNF ATPase can inhibit the growth of SCCOHT cell lines. (c) 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. C1 [Karnezis, Anthony N.; Wang, Yemin; Nielsen, Torsten O.; Gilks, C. Blake; Huntsman, David G.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Ramos, Pilar; Hendricks, William P. D.; Trent, Jeffrey M.] Translat Genom Res Inst TGen, Div Integrated Canc Genom, Phoenix, AZ USA. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [D'Angelo, Emanuela; Prat, Jaime] Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, Dept Pathol, Barcelona, Spain. [Nucci, Marisa R.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Chow, Christine; Leung, Samuel; Huntsman, David G.] Univ British Columbia, Vancouver Gen Hosp, Genet Pathol Evaluat Ctr, Vancouver, BC V5Z 1M9, Canada. [Kommoss, Friedrich] Synlab MVZ Pathol, Mannheim, Germany. [Kommoss, Stefan] Univ Hosp Tuebingen, Dept Obstet & Gynecol, Tubingen, Germany. [Silva, Annacarolina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. [Ronnett, Brigitte M.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Rabban, Joseph T.] Univ Calif San Francisco, Dept Anat Pathol, San Francisco, CA 94143 USA. [Bowtell, David D.] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Weissman, Bernard E.] Univ N Carolina, Dept Pathol & Lab Med, Lineberger Canc Ctr, Chapel Hill, NC USA. [Huntsman, David G.] British Columbia Canc Res Ctr, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada. RP Huntsman, DG (reprint author), British Columbia Canc Agcy, Res Ctr, Dept Mol Oncol, 3427-600 West 10th Ave, Vancouver, BC V5Z 4E6, Canada.; Gilks, CB (reprint author), Vancouver Gen Hosp, Dept Pathol & Lab Med, Room 1250,First Floor JPPN,910 West 10th Ave, Vancouver, BC V5Z 1M9, Canada. EM Blake.Gilks@vch.ca; dhuntsma@bccancer.bc.ca RI Bowtell, David/H-1007-2016; D'Angelo, Emanuela/J-3417-2012; Prat, Jaime/G-4679-2011; OI Bowtell, David/0000-0001-9089-7525; Silva, Annacarolina/0000-0002-0067-0288 FU National Institutes of Health [R01 CA195670-01]; Terry Fox Research Initiative New Frontiers Program in Cancer [1021]; Canadian Cancer Society Research Initiative; Terry Fox Foundation Strategic Health Research Training Program in Cancer Research at Canadian Institutes of Health Research; Anne Rita Monahan Foundation; Marsha Rivkin Center for Ovarian Cancer Research; Ovarian Cancer Alliance of Arizona; Small Cell Ovarian Cancer Foundation FX We thank the SCCOHT families and patients for their important contributions to TGen's institutional review board-approved study. We thank Drs Ralf Hass and Barbara Vanderhyden for kindly providing SCCOHT-1 and BIN67 cells, respectively. Viable frozen SCCOHT tumour cells used to establish patient-derived xenografts were obtained from Molecular Response (San Diego, CA, USA). This study was supported by grants from the National Institutes of Health (R01 CA195670-01; BEW, JMT, and DGH), the Terry Fox Research Initiative New Frontiers Program in Cancer (grant 1021; DGH), the Canadian Cancer Society Research Initiative (DGH and YW), the Terry Fox Foundation Strategic Health Research Training Program in Cancer Research at Canadian Institutes of Health Research (ANK), the Anne Rita Monahan Foundation (PR), the Marsha Rivkin Center for Ovarian Cancer Research, the Ovarian Cancer Alliance of Arizona, the Small Cell Ovarian Cancer Foundation, and philanthropic support to the TGen Foundation. NR 44 TC 18 Z9 18 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 EI 1096-9896 J9 J PATHOL JI J. Pathol. PD FEB PY 2016 VL 238 IS 3 BP 389 EP 400 DI 10.1002/path.4633 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA DC1QA UT WOS:000368990000005 PM 26356327 ER PT J AU Vanderberg, RH Farkas, AH Miller, E Sucato, GS Akers, AY Borrero, SB AF Vanderberg, Rachel H. Farkas, Amy H. Miller, Elizabeth Sucato, Gina S. Akers, Aletha Y. Borrero, Sonya B. TI Racial and/or Ethnic Differences in Formal Sex Education and Sex Education by Parents among Young Women in the United States SO JOURNAL OF PEDIATRIC AND ADOLESCENT GYNECOLOGY LA English DT Article DE Contraception; Disparities; Parents; Race; Sex education ID REPRODUCTIVE HEALTH COMMUNICATION; UNINTENDED PREGNANCY; ADOLESCENT WOMEN; DISPARITIES; PERSPECTIVES; KNOWLEDGE; ATTITUDES AB Study Objective: We sought to investigate the associations between race and/or ethnicity and young women's formal sex education and sex education by parents. Design, Setting, and Participants: Cross-sectional analysis of a nationally representative sample of 1768 women aged 15-24 years who participated in the 2011-2013 National Survey of Family Growth. Interventions and Main Outcome Measures: We assessed 6 main outcomes: participants' report of: (1) any formal sex education; (2) formal contraceptive education; (3) formal sexually transmitted infection (STI) education; (4) any sex education by parents; (5) contraceptive education by parents; and (6) STI education by parents. The primary independent variable was self-reported race and/or ethnicity. Results: Nearly all of participants (95%) reported any formal sex education, 68% reported formal contraceptive education, and 92% reported formal STI education. Seventy-five percent of participants reported not having any sex education by parents and only 61% and 56% reported contraceptive and STI education by parents, respectively. US-born Hispanic women were more likely than white women to report STI education by parents (adjusted odds ratio = 1.87; 95% confidence interval, 1.17-2.99). No other significant racial and/or ethnic differences in sex education were found. Conclusion: There are few racial and/or ethnic differences in formal sex education and sex education by parents among young women. C1 [Vanderberg, Rachel H.; Farkas, Amy H.; Borrero, Sonya B.] Univ Pittsburgh, Med Ctr, Div Gen Internal Med, Pittsburgh, PA USA. [Miller, Elizabeth; Sucato, Gina S.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Div Adolescent & Young Adult Med,Dept Pediat, Pittsburgh, PA 15213 USA. [Akers, Aletha Y.] Childrens Hosp Philadelphia, Craig Dalsimer Div Adolescent Med, Philadelphia, PA 19104 USA. [Borrero, Sonya B.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Borrero, SB (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu FU NIH [UL1-TR-000005]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [1R21HD068736-01A1] FX The authors thank Dan Winger, at the Clinical and Translation Science Institute, University of Pittsburgh, supported by NIH Grant UL1-TR-000005, for his assistance with statistical analysis. This work was also supported by Dr. Sonya Borrero's Grant 1R21HD068736-01A1 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 24 TC 0 Z9 0 U1 4 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-3188 EI 1873-4332 J9 J PEDIATR ADOL GYNEC JI J. Pediatr Adolesc. Gynecol. PD FEB PY 2016 VL 29 IS 1 BP 69 EP 73 DI 10.1016/j.jpag.2015.06.011 PG 5 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA DC1IS UT WOS:000368970600014 PM 26143556 ER PT J AU Rhee, EP AF Rhee, Eugene P. TI NADPH Oxidase 4 at the Nexus of Diabetes, Reactive Oxygen Species, and Renal Metabolism SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID NAD(P)H OXIDASE; KIDNEY; NEPHROPATHY; NOX4; EXPRESSION; INHIBITOR; FUMARATE; GLUCOSE C1 [Rhee, Eugene P.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Rhee, EP (reprint author), Thier Bldg,50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM eprhee@partners.org FU NIDDK NIH HHS [K08-DK090142, K08 DK090142] NR 20 TC 1 Z9 1 U1 2 U2 10 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2016 VL 27 IS 2 BP 337 EP 339 DI 10.1681/ASN.2015060698 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA DC1DS UT WOS:000368957600002 PM 26203117 ER PT J AU Rosales, IA Collins, AB do Carmo, PAS Tolkoff-Rubin, N Smith, RN Colvin, RB AF Rosales, Ivy A. Collins, A. Bernard do Carmo, Paula Alves S. Tolkoff-Rubin, Nina Smith, R. Neal Colvin, Robert B. TI Immune Complex Tubulointerstitial Nephritis Due to Autoantibodies to the Proximal Tubule Brush Border SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID BASEMENT-MEMBRANE; INTERSTITIAL NEPHRITIS; HEYMANN NEPHRITIS; LUPUS NEPHRITIS; ANTIBODIES; DEPOSITS; NEPHROPATHY; ANTIGENS; DISEASE; INJURY AB Immune complex tubulointerstitial nephritis due to antibodies to brush border antigens of the proximal tubule has been demonstrated experimentally and rarely in humans. Our patient developed ESRD and early recurrence after transplantation. IgG and C3 deposits were conspicuous in the tubular basement membrane of proximal tubules, corresponding to deposits observed by electron microscopy. Rare subepithelial deposits were found in the glomeruli. The patient had no evidence of SLE and had normal complement levels. Serum samples from the patient reacted with the brush border of normal human kidney, in contrast with the negative results with 20 control serum samples. Preliminary characterization of the brush border target antigen excluded megalin, CD10, and maltase. We postulate that antibodies to brush border antigens cause direct epithelial injury, accumulate in the tubular basement membrane, and elicit an interstitial inflammatory response. C1 [Rosales, Ivy A.; Collins, A. Bernard; Smith, R. Neal; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Thier 831A, Boston, MA 02114 USA. [Tolkoff-Rubin, Nina] Massachusetts Gen Hosp, Renal Transplantat Program, Div Nephrol, Boston, MA 02114 USA. [do Carmo, Paula Alves S.] Ctr Especializado Anat Patol, Belo Horizonte, MG, Brazil. RP Rosales, IA (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Thier 831A, Boston, MA 02114 USA. EM irosales@mgh.harvard.edu FU International Society of Nephrology Fellowship Grant FX This work was made possible through an International Society of Nephrology Fellowship Grant to I.A.R. NR 16 TC 1 Z9 1 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2016 VL 27 IS 2 BP 380 EP 384 DI 10.1681/ASN.2015030334 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA DC1DS UT WOS:000368957600008 PM 26334028 ER PT J AU van Ballegooijen, AJ Rhee, EP Elmariah, S de Boer, IH Kestenbaum, B AF van Ballegooijen, Adriana J. Rhee, Eugene P. Elmariah, Sammy de Boer, Ian H. Kestenbaum, Bryan TI Renal Clearance of Mineral Metabolism Biomarkers SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; MOLECULAR-WEIGHT PROTEINS; PARATHYROID-HORMONE; HALF-LIFE; FGF-23; CATABOLISM; DISORDERS; TRANSPORT; FRAGMENT AB CKD leads to disturbances in multiple interrelated hormones that regulate bone and mineral metabolism. The renal handling of mineral metabolism hormones in humans is incompletely understood. We determined the single-pass renal clearance of parathyroid hormone, fibroblast growth factor 23, vitamin D metabolites, and phosphate from paired blood samples collected from the abdominal aorta and renal vein in 17 participants undergoing simultaneous right and left heart catheterization and estimated associations of eGFR with the renal elimination of metabolites. The mean age +/- SD of the study population was 71.4 +/- 10.0 years and 11 participants (65%) were male. We found a relatively large mean +/- SD single-pass renal extraction of parathyroid hormone (44.2%+/- 10.3%) that exceeded the extraction of creatinine (22.1%+/- 7.9%). The proportionate renal extraction of parathyroid hormone correlated with eGFR. The renal extraction of fibroblast growth factor 23 was, on average, lower than that of parathyroid hormone with greater variability across individuals (17.1%+/- 19.5%). There were no differences in the mean concentrations of vitamin D metabolites across the renal vein and artery. In summary, we demonstrate substantial single-pass renal extraction of parathyroid hormone at a rate that exceeds glomerular filtration. Impaired renal clearance of parathyroid hormone may contribute to secondary hyperparathyroidism in CKD. C1 [van Ballegooijen, Adriana J.; de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Rhee, Eugene P.] Massachusetts Gen Hosp, Nephrol Div, Boston, MA 02114 USA. [Rhee, Eugene P.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Elmariah, Sammy] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Elmariah, Sammy] Harvard Clin Res Inst, Boston, MA USA. RP van Ballegooijen, AJ (reprint author), Kidney Res Inst, Box 35906, Seattle, WA USA. EM hvb2@uw.edu FU Niels Stensen Fellowship; Extramural Grant Program by Satellite Healthcare; NIH [K08-DK090142, R01-DK099199] FX This research was supported by the Niels Stensen Fellowship 2014, the Extramural Grant Program by Satellite Healthcare, and NIH grants K08-DK090142 and R01-DK099199. NR 21 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2016 VL 27 IS 2 BP 392 EP 397 DI 10.1681/ASN.2014121253 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DC1DS UT WOS:000368957600010 PM 26047790 ER PT J AU Deo, R Shou, HC Soliman, EZ Yang, W Arkin, JM Zhang, XM Townsend, RR Go, AS Shlipak, MG Feldman, HI AF Deo, Rajat Shou, Haochang Soliman, Elsayed Z. Yang, Wei Arkin, Joshua M. Zhang, Xiaoming Townsend, Raymond R. Go, Alan S. Shlipak, Michael G. Feldman, Harold I. TI Electrocardiographic Measures and Prediction of Cardiovascular and Noncardiovascular Death in CKD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HEART-ASSOCIATION ELECTROCARDIOGRAPHY; OF-CARDIOLOGY-FOUNDATION; LEFT-VENTRICULAR HYPERTROPHY; SUDDEN CARDIAC DEATH; SERVICES TASK-FORCE; ARRHYTHMIAS COMMITTEE; SCIENTIFIC STATEMENT; CLINICAL CARDIOLOGY; RHYTHM-SOCIETY; AHA/ACCF/HRS RECOMMENDATIONS AB Limited studies have assessed the resting 12-lead electrocardiogram (ECG) as a screening test in intermediate risk populations. We evaluated whether a panel of common ECG parameters are independent predictors of mortality risk in a prospective cohort of participants with CKD. The Chronic Renal Insufficiency Cohort (CRIC) study enrolled 3939 participants with eGFR<70 ml/min per 1.73 m(2) from June 2003 to September 2008. Over a median follow-up of 7.5 years, 750 participants died. After adjudicating the initial 497 deaths, we identified 256 cardiovascular and 241 noncardiovascular deaths. ECG metrics were independent risk markers for cardiovascular death (hazard ratio, 95% confidence interval): PR interval >= 200 ms (1.62, 1.19-2.19); QRS interval 100-119 ms (1.64, 1.20-2.25) and >= 120 ms (1.75, 1.17-2.62); corrected QT (QTc) interval >= 450 ms in men or >= 460 ms in women (1.72, 1.19-2.49); and heart rate 60-90 beats per minute (1.21, 0.89-1.63) and >= 90 beats per minute (2.35, 1.03-5.33). Most ECG measures were stronger markers of risk for cardiovascular death than for all-cause mortality or noncardiovascular death. Adding these intervals to a comprehensive model of cardiorenal risk factors increased the C-statistic for cardiovascular death from 0.77 to 0.81 (P<0.001). Furthermore, adding ECG metrics to the model adjusted for standard risk factors resulted in a net reclassification of 12.1% (95% confidence interval 8.1%-16.0%). These data suggest common ECG metrics are independent risk factors for cardiovascular death and enhance the ability to predict death events in a population with CKD. C1 [Deo, Rajat; Arkin, Joshua M.] Univ Penn, Cardiac Electrophysiol Sect, Div Cardiovasc Med, Dept Med,Perelman Sch Med, Philadelphia, PA 19104 USA. [Shou, Haochang; Yang, Wei; Zhang, Xiaoming; Feldman, Harold I.] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shou, Haochang; Yang, Wei; Zhang, Xiaoming; Feldman, Harold I.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Sch Med, Dept Internal Med, Cardiol Sect, Winston Salem, NC 27109 USA. [Townsend, Raymond R.; Feldman, Harold I.] Univ Penn, Renal Electrolyte & Hypertens Div, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Go, Alan S.] Stanford Univ, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. [Go, Alan S.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol Biostat & Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA USA. RP Deo, R (reprint author), 3400 Spruce St,9 Founders Cardiol, Philadelphia, PA 19146 USA. EM Rajat.Deo@uphs.upenn.edu FU National Institutes of Health (NIH) [K23-DK089118]; National Institute of Diabetes and Digestive and Kidney Diseases [U01-DK060990, U01-DK060984, U01-DK061022, U01-DK061021, U01-DK061028, U01-DK060980, U01-DK060963, U01-DK060902]; Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/ National Center for Advancing Translational Sciences (NCATS) [UL1-TR000003]; Johns Hopkins University [UL1-TR000424]; University of Maryland [M01-RR16500]; Clinical and Translational Science Collaborative of Cleveland from the NCATS component of the NIH and NIH roadmap for Medical Research [UL1-TR000439]; Michigan Institute for Clinical and Health Research Grant [UL1-TR000433]; University of Illinois at Chicago CTSA Grant [UL1-RR029879]; Tulane University Translational Research in Hypertension and Renal Biology Grant [P30-GM103337]; Kaiser Permanente NIH/NCRR UCSF-CTSI Grant [UL1-RR024131] FX We appreciate the support of the other CRIC Study Investigators including Lawrence J. Appel, Jiang He, John W. Kusek, James P. Lash, Akinlolu Ojo, and Mahboob Rahman. The CRIC ancillary study was supported by the National Institutes of Health (NIH) grant K23-DK089118 (to R.D.). The CRIC study is supported by cooperative agreement project grants from the National Institute of Diabetes and Digestive and Kidney Diseases (U01-DK060990, U01-DK060984, U01-DK061022, U01-DK061021, U01-DK061028, U01-DK060980, U01-DK060963, and U01-DK060902).; In addition, this work was supported in part by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/ National Center for Advancing Translational Sciences (NCATS) Grant UL1-TR000003, Johns Hopkins University Grant UL1-TR000424, University of Maryland GCRC Grant M01-RR16500, Clinical and Translational Science Collaborative of Cleveland Grant UL1-TR000439 from the NCATS component of the NIH and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research Grant UL1-TR000433, University of Illinois at Chicago CTSA Grant UL1-RR029879, Tulane University Translational Research in Hypertension and Renal Biology Grant P30-GM103337, and Kaiser Permanente NIH/NCRR UCSF-CTSI Grant UL1-RR024131. NR 33 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2016 VL 27 IS 2 BP 559 EP 569 DI 10.1681/ASN.2014101045 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA DC1DS UT WOS:000368957600025 PM 26160896 ER PT J AU Sundt, TM AF Sundt, Thoralf M. TI Decisions, decisions: Chocolate, vanilla, or something else? SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 [Sundt, Thoralf M.] Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St, Boston, MA 02114 USA. [Sundt, Thoralf M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St, Boston, MA 02114 USA. EM tsundt@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 2016 VL 151 IS 2 BP 339 EP 340 DI 10.1016/j.jtcvs.2015.10.103 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DB8ZR UT WOS:000368806200028 PM 26651964 ER PT J AU Garcia, JP Rajagopal, K AF Garcia, Jose P. Rajagopal, Keshava TI Ex vivo lung perfusion: Theme and variation SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 [Garcia, Jose P.] Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,Cox Bldg 642, Boston, MA 02114 USA. [Rajagopal, Keshava] Texas Med Ctr, Mem Hermann Hosp, Ctr Adv Heart Failure, Dept Cardiovasc Surg, Houston, TX USA. RP Garcia, JP (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,Cox Bldg 642, Boston, MA 02114 USA. EM jgarcia@partners.org NR 7 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 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 2016 VL 151 IS 2 BP 576 EP 577 DI 10.1016/j.jtcvs.2015.06.055 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DB8ZR UT WOS:000368806200075 PM 26232315 ER PT J AU Kinloch, NN MacMillan, DR Le, AQ Cotton, LA Bangsberg, DR Buchbinder, S Carrington, M Fuchs, J Harrigan, PR Koblin, B Kushel, M Markowitz, M Mayer, K Milloy, MJ Schechter, MT Wagner, T Walker, BD Carlson, JM Poon, AFY Brumme, ZL AF Kinloch, Natalie N. MacMillan, Daniel R. Le, Anh Q. Cotton, Laura A. Bangsberg, David R. Buchbinder, Susan Carrington, Mary Fuchs, Jonathan Harrigan, P. Richard Koblin, Beryl Kushel, Margot Markowitz, Martin Mayer, Kenneth Milloy, M. J. Schechter, Martin T. Wagner, Theresa Walker, Bruce D. Carlson, Jonathan M. Poon, Art F. Y. Brumme, Zabrina L. TI Population-Level Immune-Mediated Adaptation in HIV-1 Polymerase during the North American Epidemic SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE ESCAPE; SAN-FRANCISCO; CLASS-I; VANCOUVER LYMPHADENOPATHY; CELL RESPONSES; PHYLOGENETIC ANALYSIS; DISEASE PROGRESSION; HOMOSEXUAL-MEN; VIRAL-LOAD AB Human leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA-associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989; n = 338) and modern (2001 to 2011; n = 278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2-fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average similar to 2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era. C1 [Kinloch, Natalie N.; MacMillan, Daniel R.; Le, Anh Q.; Cotton, Laura A.; Poon, Art F. Y.; Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Bangsberg, David R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bangsberg, David R.; Mayer, Kenneth] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Buchbinder, Susan; Fuchs, Jonathan; Wagner, Theresa] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Buchbinder, Susan; Fuchs, Jonathan; Kushel, Margot] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Carrington, Mary] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA. [Carrington, Mary; Walker, Bruce D.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard U, Cambridge, MA USA. [Harrigan, P. Richard; Milloy, M. J.; Poon, Art F. Y.; Brumme, Zabrina L.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Harrigan, P. Richard; Milloy, M. J.; Schechter, Martin T.; Poon, Art F. Y.] Univ British Columbia, Fac Med, Vancouver, BC, Canada. [Koblin, Beryl] New York Blood Ctr, New York, NY 10021 USA. [Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Mayer, Kenneth] Fenway Community Hlth, Boston, MA USA. [Carlson, Jonathan M.] Microsoft Res, Seattle, WA USA. RP Brumme, ZL (reprint author), Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada.; Brumme, ZL (reprint author), British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. EM zbrumme@sfu.ca FU Frederick National Laboratory for Cancer Research [HHSN261200800001E]; Intramural Research Program of the NIH, Frederick National Laboratory for Cancer Research; Gouvernement du Canada \ Canadian Institutes of Health Research (CIHR) [MOP-93536, HOP-115700]; Michael Smith Foundation for Health Research (MSFHR) FX Frederick National Laboratory for Cancer Research provided funding to Mary Carrington under grant number HHSN261200800001E. Intramural Research Program of the NIH, Frederick National Laboratory for Cancer Research provided funding to Mary Carrington. Gouvernement du Canada vertical bar Canadian Institutes of Health Research (CIHR) provided funding to Natalie N. Kinloch, Anh Q. Le, Art F. Y. Poon, Zabrina L. Brumme. Michael Smith Foundation for Health Research (MSFHR) provided funding to Art F. Y. Poon and Zabrina L. Brumme. Gouvernement du Canada vertical bar Canadian Institutes of Health Research (CIHR) provided funding to Zabrina L. Brumme under grant number MOP-93536. Gouvernement du Canada vertical bar Canadian Institutes of Health Research (CIHR) provided funding to Art F. Y. Poon and Zabrina L. Brumme under grant number HOP-115700. NR 81 TC 0 Z9 0 U1 1 U2 3 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 FEB PY 2016 VL 90 IS 3 BP 1244 EP 1258 DI 10.1128/JVI.02353-15 PG 15 WC Virology SC Virology GA DC3WW UT WOS:000369150800008 ER PT J AU Kearney, MF Wiegand, A Shao, W Coffin, JM Mellors, JW Lederman, M Gandhi, RT Keele, BF Li, JZ AF Kearney, Mary F. Wiegand, Ann Shao, Wei Coffin, John M. Mellors, John W. Lederman, Michael Gandhi, Rajesh T. Keele, Brandon F. Li, Jonathan Z. TI Origin of Rebound Plasma HIV Includes Cells with Identical Proviruses That Are Transcriptionally Active before Stopping of Antiretroviral Therapy SO JOURNAL OF VIROLOGY LA English DT Article ID SEQUENTIAL 3-DRUG REGIMENS; INFECTED-CELLS; TREATMENT INTERRUPTION; REVERSE-TRANSCRIPTASE; CONTROLLED-TRIAL; INITIAL THERAPY; REPLICATION; RESERVOIR; DISCONTINUATION; PROLIFERATION AB Understanding the origin of HIV variants during viral rebound may provide insight into the composition of the HIV reservoir and has implications for the design of curative interventions. HIV single-genome sequences were obtained from 10 AIDS Clinical Trials Group participants who underwent analytic antiretroviral therapy (ART) interruption (ATI). Rebounding variants were compared with those in pre-ART plasma in all 10 participants and with on-ART peripheral blood mononuclear cell (PBMC)-associated DNA and RNA (CA-RNA) in 7/10 participants. The highest viral diversities were found in the DNA and CA-RNA populations. In 3 of 7 participants, we detected multiple, identical DNA and CA-RNA sequences during suppression on ART that exactly matched plasma HIV sequences. Hypermutated DNA and CA-RNA were detected in four participants, contributing to diversities in these compartments that were higher than in the pre-ART and post-ATI plasma. Shifts in the viral rebound populations could be detected in some participants over the 2- to 3-month observation period. These findings suggest that a source of initial rebound viremia could be populations of infected cells that clonally expanded prior to and/or during ART, some of which were already expressing HIV RNA before treatment was interrupted. These clonally expanding populations of HIV-infected cells may represent an important target for strategies aimed at achieving reservoir reduction and sustained virologic remission. C1 [Kearney, Mary F.; Wiegand, Ann] NCI, HIV Dynam & Replicat Program, Frederick, MD 21701 USA. [Shao, Wei; Keele, Brandon F.] Leidos Biomed Res Inc, Frederick Natl Labs Canc Res, Frederick, MD USA. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Mellors, John W.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Lederman, Michael] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Gandhi, Rajesh T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Li, Jonathan Z.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Keele, BF (reprint author), Leidos Biomed Res Inc, Frederick Natl Labs Canc Res, Frederick, MD USA.; Li, JZ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. EM kearneym@ncifcrf.gov; jli@bwh.harvard.edu FU National Institutes of Health (NIH) [AI100699, U01AI068636, UM1AI106701]; Leidos Biomedical Research, Inc. [12XS547, 13SX110]; NIH [HHSN261200800001E]; National Cancer Institute; AIDS Targeted Antiviral Program Award; FM Kirby Foundation FX This work was supported by National Institutes of Health (NIH) grants AI100699 (to J.Z.L.), U01AI068636 (to the AIDS Clinical Trials Group), and UM1AI106701 (to the Pittsburgh Virology Specialty Laboratory), and by Leidos Biomedical Research, Inc. (subcontract 12XS547 to J.W.M. and 13SX110 to J.M.C. through the National Cancer Institute), and by intramural NIH funding, including the National Cancer Institute, the AIDS Targeted Antiviral Program Award to M.F.K., and NIH Contract No. HHSN261200800001E. J.M.C. was a Research Professor of the American Cancer Society, with support from the FM Kirby Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 33 TC 9 Z9 9 U1 2 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 FEB PY 2016 VL 90 IS 3 BP 1369 EP 1376 DI 10.1128/JVI.02139-15 PG 8 WC Virology SC Virology GA DC3WW UT WOS:000369150800018 PM 26581989 ER PT J AU Lee, WS Richard, J Lichtfuss, M Smith, AB Park, J Courter, JR Melillo, BN Sodroski, JG Kaufmann, DE Finzi, A Parsons, MS Kent, SJ AF Lee, Wen Shi Richard, Jonathan Lichtfuss, Marit Smith, Amos B., III Park, Jongwoo Courter, Joel R. Melillo, Bruno N. Sodroski, Joseph G. Kaufmann, Daniel E. Finzi, Andres Parsons, Matthew S. Kent, Stephen J. TI Antibody-Dependent Cellular Cytotoxicity against Reactivated HIV-1-Infected Cells SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LATENTLY INFECTED-CELLS; VACCINE EFFICACY TRIAL; CD4(+) T-CELLS; NK CELLS; MEDIATED CYTOTOXICITY; HIV-1 GP120; DISEASE PROGRESSION; IN-VITRO; EX-VIVO AB Lifelong antiretroviral therapy (ART) for HIV-1 does not diminish the established latent reservoir. A possible cure approach is to reactivate the quiescent genome from latency and utilize immune responses to eliminate cells harboring reactivated HIV-1. It is not known whether antibodies within HIV-1-infected individuals can recognize and eliminate cells reactivated from latency through antibody-dependent cellular cytotoxicity (ADCC). We found that reactivation of HIV-1 expression in the latently infected ACH-2 cell line elicited antibody-mediated NK cell activation but did not result in antibody-mediated killing. The lack of CD4 expression on these HIV-1 envelope (Env)-expressing cells likely resulted in poor recognition of CD4-induced antibody epitopes on Env. To examine this further, cultured primary CD4(+) T cells from HIV-1(+) subjects were used as targets for ADCC. These ex vivo-expanded primary cells were modestly susceptible to ADCC mediated by autologous or heterologous HIV-1(+) serum antibodies. Importantly, ADCC mediated against these primary cells could be enhanced following incubation with a CD4-mimetic compound (JP-III-48) that exposes CD4-induced antibody epitopes on Env. Our studies suggest that with sufficient reactivation and expression of appropriate Env epitopes, primary HIV-1-infected cells can be targets for ADCC mediated by autologous serum antibodies and innate effector cells. The results of this study suggest that further investigation into the potential of ADCC to eliminate reactivated latently infected cells is warranted. C1 [Lee, Wen Shi; Lichtfuss, Marit; Parsons, Matthew S.; Kent, Stephen J.] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia. [Richard, Jonathan; Kaufmann, Daniel E.; Finzi, Andres] CHUM, Ctr Rech, Montreal, PQ, Canada. [Richard, Jonathan; Finzi, Andres] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada. [Smith, Amos B., III; Park, Jongwoo; Courter, Joel R.; Melillo, Bruno N.] Univ Penn, Sch Arts & Sci, Dept Chem, Philadelphia, PA 19104 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & Virol, 44 Binney St, Boston, MA 02115 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, 44 Binney St, Boston, MA 02115 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 44 Binney St, Boston, MA 02115 USA. [Kaufmann, Daniel E.] MIT & Harvard, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA USA. [Kaufmann, Daniel E.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Kaufmann, Daniel E.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Finzi, Andres] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. [Kent, Stephen J.] Monash Univ, Melbourne Sexual Hlth Ctr, Cent Clin Sch, Clayton, Vic 3800, Australia. [Kent, Stephen J.] Monash Univ, Dept Infect Dis, Clayton, Vic 3800, Australia. [Kent, Stephen J.] Univ Melbourne, ARC Ctr Excellence Convergent Bionano Sci & Techn, Melbourne, Vic 3010, Australia. RP Kent, SJ (reprint author), Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia.; Finzi, A (reprint author), CHUM, Ctr Rech, Montreal, PQ, Canada.; Finzi, A (reprint author), Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada.; Finzi, A (reprint author), McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada.; Kent, SJ (reprint author), Monash Univ, Melbourne Sexual Hlth Ctr, Cent Clin Sch, Clayton, Vic 3800, Australia.; Kent, SJ (reprint author), Monash Univ, Dept Infect Dis, Clayton, Vic 3800, Australia. EM andres.finzi@umontreal.ca; skent@unimelb.edu.au OI Kent, Stephen/0000-0002-8539-4891 FU Australia NHMRC [1052979, 10471832]; Australia-India Strategic Research Fund; Canada Foundation for Innovation Program Leader; Canadian Institutes for Health Research (CIHR) [119334, 134117]; Establishment of Young Scientist [26702]; FRQS AIDS and Infectious Diseases Network; NIH [AI100645, AI100663, GM56550]; Center for HIV/AIDS Vaccine Immunology and Immunogen Design (CHAVI-ID); National Institutes of Health [RO1 HL-092565]; Canada Research Chair on Retroviral Entry; CIHR Fellowship Awards; Research Scholar Career Award from the Quebec Health Research Fund (FQRS) FX This work was supported by Australia NHMRC awards 1052979 and 10471832, an Australia-India Strategic Research Fund award, a Canada Foundation for Innovation Program Leader grant, Canadian Institutes for Health Research (CIHR) operating grants 119334 and 134117, Establishment of Young Scientist grant 26702 to A.F., the FRQS AIDS and Infectious Diseases Network, NIH grants AI100645, AI100663, and GM56550, and Center for HIV/AIDS Vaccine Immunology and Immunogen Design (CHAVI-ID) and National Institutes of Health grant RO1 HL-092565. A.F. is a recipient of a Canada Research Chair on Retroviral Entry. J.R. and M.S.P. are recipients of CIHR Fellowship Awards. D.E.K. is supported by a Research Scholar Career Award from the Quebec Health Research Fund (FQRS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 4 Z9 4 U1 3 U2 10 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 FEB PY 2016 VL 90 IS 4 BP 2021 EP 2030 DI 10.1128/JVI.02717-15 PG 10 WC Virology SC Virology GA DC3XL UT WOS:000369152700028 PM 26656700 ER PT J AU Patti, ME Goldfine, AB AF Patti, Mary-Elizabeth Goldfine, Allison B. TI The rollercoaster of post-bariatric hypoglycaemia SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Editorial Material ID GASTRIC BYPASS-SURGERY; SLEEVE GASTRECTOMY; MIXED MEAL; NEUROGLYCOPENIA; SYMPTOMS; RISK C1 [Patti, Mary-Elizabeth; Goldfine, Allison B.] Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. [Patti, Mary-Elizabeth; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA.; Patti, ME (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM mary.elizabeth.patti@joslin.harvard.edu NR 14 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD FEB PY 2016 VL 4 IS 2 BP 94 EP 96 DI 10.1016/S2213-8587(15)00460-X PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB7OL UT WOS:000368705000010 PM 26701701 ER PT J AU Shanbhogue, VV Mitchell, DM Rosen, CJ Bouxsein, ML AF Shanbhogue, Vikram V. Mitchell, Deborah M. Rosen, Clifford J. Bouxsein, Mary L. TI Type 2 diabetes and the skeleton: new insights into sweet bones SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Review ID DEPENDENT INSULINOTROPIC PEPTIDE; PREVALENT VERTEBRAL DEFORMITIES; RANDOMIZED CLINICAL-TRIALS; ISLET AMYLOID POLYPEPTIDE; COLLAGEN CROSS-LINKING; FORMATION IN-VIVO; MINERAL DENSITY; FRACTURE RISK; POSTMENOPAUSAL WOMEN; BODY-COMPOSITION AB Substantial evidence shows that skeletal fragility should be considered among the complications associated with type 2 diabetes. Individuals with type 2 diabetes have increased fracture risk, despite normal bone mineral density (BMD) and high BMI-factors that are generally protective against fractures. The mechanisms underlying skeletal fragility in diabetes are not completely understood, but are multifactorial and likely include effects of obesity, hyperglycaemia, oxidative stress, and accumulation of advanced glycation end products, leading to altered bone metabolism, structure, and strength. Clinicians should be aware that BMD measurements underestimate fracture risk in people with type 2 diabetes, and that new treatments for diabetes, with neutral or positive effects on skeletal health, might play a part in the management of diabetes in those at high risk of fracture. Data for the optimum management of osteoporosis in patients with type 2 diabetes are scarce, but in the absence of evidence to the contrary, physicians should follow guidelines established for postmenopausal osteoporosis. C1 [Shanbhogue, Vikram V.] Univ Southern Denmark, Odense Univ Hosp, Dept Endocrinol, Odense, Denmark. [Shanbhogue, Vikram V.] Univ Southern Denmark, Inst Clin Res, Odense, Denmark. [Mitchell, Deborah M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Rosen, Clifford J.] Maine Med Ctr, Res Inst, Ctr Clin & Translat Res, Scarborough, ME USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA. [Bouxsein, Mary L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bouxsein, ML (reprint author), Beth Israel Deaconess Med Ctr, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA. EM mbouxsei@bidmc.harvard.edu FU Danish PhD School of Endocrinology; National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [R24DK092759, P30DK057521] FX We acknowledge funding support from The Danish PhD School of Endocrinology and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers R24DK092759 and P30DK057521. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 137 TC 15 Z9 16 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD FEB PY 2016 VL 4 IS 2 BP 159 EP 173 DI 10.1016/S2213-8587(15)00283-1 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB7OL UT WOS:000368705000027 PM 26365605 ER PT J AU Gray, ST Sadow, PM Lin, DT Sedaghat, AR AF Gray, Stacey T. Sadow, Peter M. Lin, Derrick T. Sedaghat, Ahmad R. TI Endoscopic sinus surgery for chronic rhinosinusitis in patients previously treated for sinonasal malignancy SO LARYNGOSCOPE LA English DT Article DE Chronic rhinosinusitis; endoscopic sinus surgery; complications; sinonasal malignancy ID NASOPHARYNGEAL CARCINOMA PATIENTS; SINGLE-INSTITUTION-EXPERIENCE; PARA-NASAL SINUSES; PARANASAL SINUSES; SKULL BASE; CRANIOFACIAL RESECTION; RADIATION-THERAPY; COMPLICATIONS; CANCER; EPIDEMIOLOGY AB Objectives/HypothesisPatients with a history of sinonasal malignancy can develop chronic rhinosinusitis (CRS) as a consequence of their oncologic treatment. Some patients will fail medical management and require endoscopic sinus surgery (ESS). This study reviews the use of ESS in the management of CRS in patients previously treated for sinonasal malignancy. Study DesignRetrospective review. MethodsAll patients with a history of sinonasal malignancy who developed CRS and underwent ESS were reviewed. Preoperative and postoperative imaging and symptoms were collected. Major complications (bleeding, orbital injury, and cerebrospinal fluid leak) and minor complications (adhesion formation) and postoperative healing were reviewed. ResultsEighteen patients were identified. All patients presented with symptoms of CRS and sinonasal crusting. Additionally, five patients presented with recurrent facial cellulitis, and six patients had mucoceles. No major complications were encountered. Postoperatively, all patients reported a subjective improvement in their sinonasal symptoms. Comparison of pre- and post-ESS imaging revealed a significant improvement in Lund-Mackay scores after ESS (P<0.001) from 12.8 (range 5-22) to 7 (range). Despite symptomatic improvement, all patients continued to have nasal crusting. All patients who initially presented with recurrent facial cellulitis had no further episodes after ESS. None of the endoscopically drained mucoceles recurred. ConclusionFor patients previously treated for sinonasal malignancy with refractory CRS, ESS appears to be a safe and effective treatment option. ESS in these patients results in subjective improvement in sinonasal symptoms as well as objective improvement in radiographic CRS disease burden, although sinonasal crusting will likely not resolve. Level of Evidence4. Laryngoscope, 126:304-315, 2016 C1 [Gray, Stacey T.; Lin, Derrick T.; Sedaghat, Ahmad R.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm,Massachusetts Gen, Boston, MA 02115 USA. [Gray, Stacey T.; Lin, Derrick T.; Sedaghat, Ahmad R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Gray, ST (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM stacey_gray@meei.harvard.edu NR 62 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 FEB PY 2016 VL 126 IS 2 BP 304 EP 315 DI 10.1002/lary.25435 PG 12 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA DC1SX UT WOS:000368998200010 PM 26309057 ER PT J AU Meier, JC Remenschneider, AK Gray, ST Holbrook, EH Gliklich, RE Metson, R AF Meier, Josh C. Remenschneider, Aaron K. Gray, Stacey T. Holbrook, Eric H. Gliklich, Richard E. Metson, Ralph TI The impact of surgical trainee participation on sinus surgery outcomes SO LARYNGOSCOPE LA English DT Article DE Quality of life; allergy; rhinology; outcomes; cost-effectiveness; adult rhinology ID QUALITY-IMPROVEMENT-PROGRAM; RESIDENT INVOLVEMENT; CHRONIC RHINOSINUSITIS; ACS-NSQIP; COMPLICATION RATES; CLINICAL-OUTCOMES; AMERICAN-COLLEGE; HEALTH STATES; EDUCATION; MORBIDITY AB Objectives/HypothesisTo determine the effect of otolaryngology trainee participation on clinical outcomes in patients who undergo endoscopic sinus surgery (ESS) for chronic rhinosinusitis. Study DesignSecondary analysis of prospectively collected data. MethodsPatients enrolled in a sinus surgery outcomes study between May 2011 and March 2013 were stratified into two groupsthose who were operated on by an attending alone and those operated on by an attending with a trainee present (resident, fellow, or both). Patients completed quality of life (QOL) surveys including the Chronic Sinusitis Survey (CSS), 22-item Sino-Nasal Outcome Test (SNOT-22), and EuroQol 5-dimension survey preoperatively and 1 year postoperatively. Operative time, estimated blood loss (EBL), complication rates, and survey scores were compared between groups. ResultsThe study population consisted of 452 patients. The attending alone (n=119) and trainee (n=333) groups were statistically comparable in terms of patient demographics, disease severity, and extent of surgery. Mean operative time was significantly shorter in the attending-alone group (80.0 vs. 90.6 minutes, P<.01). Mean EBL (105 mL attending vs. 117 mL trainee, P=.39) and complication rates (3.3% attending vs. 0.6% trainee, P=.07) were similar between groups. Observed changes in QOL measures following ESS were comparable between groups, although absolute improvement in the SNOT-22 scores (19.0 attending vs. 24.5 trainee, P=.05) did show a trend toward greater improvement in the trainee group. ConclusionsTrainee participation in ESS is associated with prolongation in surgical time; however, such participation was not found to adversely affect patient safety or clinical outcomes. Level of Evidence2b Laryngoscope, 126:316-321, 2016 C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Meier, JC (reprint author), 9770 S McCarran Blvd, Reno, NV 89523 USA. EM meier_josh@yahoo.com FU Board Committee on Quality at the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts FX This work was supported by a funding grant from the Board Committee on Quality at the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. NR 39 TC 1 Z9 1 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 FEB PY 2016 VL 126 IS 2 BP 316 EP 321 DI 10.1002/lary.25504 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA DC1SX UT WOS:000368998200011 PM 26360316 ER PT J AU Gin, JL Kranke, D Saia, R Dobalian, A AF Gin, June L. Kranke, Derrick Saia, Rebecca Dobalian, Aram TI Disaster Preparedness in Homeless Residential Organizations in Los Angeles County: Identifying Needs, Assessing Gaps SO NATURAL HAZARDS REVIEW LA English DT Article DE Disasters; Residential organizations; Disaster planning; Preparedness; Homeless persons; Emergency management; Vulnerable populations ID HEALTH-CARE; COMMUNITY AB Community-based organizations (CBOs) are essential to supporting homeless populations during disasters, yet little is known about their preparedness and ability to support their vulnerable clients. This qualitative study evaluated the perceptions of Los Angeles nonprofit homeless residential service providers regarding the likely impacts of a disaster on their clients and operations, the barriers they face in disaster planning, and their suggested solutions to facilitate preparedness within their sector. Twelve semistructured interviews were conducted with executive staff and emergency planners from six organizations serving people experiencing homelessness. Respondents reported significant barriers to both postdisaster services and collaboration with emergency management. They indicated both a need for and interest in technical assistance and training to develop their disaster capabilities. These concerns suggest that a multisector effort, including homeless-service organizations, their funders, and emergency managers, is needed to strengthen the resilience of safety-net CBOs serving homeless populations. This work is made available under the terms of the Creative Commons Attribution 4.0 International license, http://creativecommons. org/licenses/by/4.0/. C1 [Gin, June L.; Kranke, Derrick; Saia, Rebecca; Dobalian, Aram] US Dept Vet Affairs, Vet Emergency Management Evaluat Ctr, 16111 Plummer St,MS 152, North Hills, CA 91343 USA. [Dobalian, Aram] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Dobalian, Aram] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. RP Gin, JL (reprint author), US Dept Vet Affairs, Vet Emergency Management Evaluat Ctr, 16111 Plummer St,MS 152, North Hills, CA 91343 USA. EM June.Gin@va.gov; Derrick.Kranke@va.gov; Rebecca.Saia@va.gov; Aram.Dobalian@va.gov NR 46 TC 0 Z9 0 U1 5 U2 8 PU ASCE-AMER SOC CIVIL ENGINEERS PI RESTON PA 1801 ALEXANDER BELL DR, RESTON, VA 20191-4400 USA SN 1527-6988 EI 1527-6996 J9 NAT HAZARDS REV JI Nat. Hazards Rev. PD FEB PY 2016 VL 17 IS 1 AR 04015022 DI 10.1061/(ASCE)NH.1527-6996.0000208 PG 8 WC Engineering, Civil; Environmental Studies; Geosciences, Multidisciplinary; Meteorology & Atmospheric Sciences; Water Resources SC Engineering; Environmental Sciences & Ecology; Geology; Meteorology & Atmospheric Sciences; Water Resources GA DB9LK UT WOS:000368837300016 ER PT J AU Weaver, GC Villar, RF Kanekiyo, M Nabel, GJ Mascola, JR Lingwood, D AF Weaver, Grant C. Villar, Rina F. Kanekiyo, Masaru Nabel, Gary J. Mascola, John R. Lingwood, Daniel TI In vitro reconstitution of B cell receptor-antigen interactions to evaluate potential vaccine candidates SO NATURE PROTOCOLS LA English DT Article ID NEUTRALIZING ANTIBODIES; HEMAGGLUTININ-STEM; INFLUENZA ANTIBODIES; MEMORY; RECOGNITION; EXPRESSION; MATURATION; IMMUNOGEN; RESPONSES; BINDING AB Predicting immune responses before vaccination is challenging because of the complexity of the governing parameters. Nevertheless, recent work has shown that B cell receptor (BCR)-antigen engagement in vitro can prove a powerful means of informing the design of antibody-based vaccines. We have developed this principle into a two-phased immunogen evaluation pipeline to rank-order vaccine candidates. In phase 1, recombinant antigens are screened for reactivity to the germline precursors that produce the antibody responses of interest. To both mimic the architecture of initial antigen engagement and facilitate rapid immunogen screening, these antibodies are expressed as membrane-anchored IgM (mIgM) in 293F indicator cells. In phase 2, the binding hits are multimerized by nanoparticle or proteoliposome display, and they are evaluated for BCRCR triggering in an engineered B cell line displaying the IgM sequences of interest. Key developments that complement existing methodology in this area include the following: (i) introduction of a high-throughput screening step before evaluation of more time-intensive BCRCR-triggering analyses; (ii) generalizable multivalent antigen-display platforms needed for BCRCR activation; and (iii) engineered use of a human B cell line that does not display endogenous antibody, but only ectopically expressed BCRCR sequences of interest. Through this pipeline, the capacity to initiate favorable antibody responses is evaluated. The entire protocol can be completed within 2.5 months. C1 [Weaver, Grant C.; Villar, Rina F.; Lingwood, Daniel] MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Weaver, Grant C.; Villar, Rina F.; Lingwood, Daniel] Harvard Univ, Cambridge, MA 02138 USA. [Kanekiyo, Masaru; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Nabel, Gary J.] Sanofi, Cambridge, MA USA. RP Lingwood, D (reprint author), MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Lingwood, D (reprint author), Harvard Univ, Cambridge, MA 02138 USA. EM dlingwood@mgh.harvard.edu FU Harvard University Center for AIDS Research (CFAR) grant [P30 AI060354]; Broad-Ragon ENDHIV Catalytic grant; William F. Milton Fund; Gilead Sciences Research Scholars Program in HIV FX The authors thank members of the Lingwood laboratory for critical reading of the manuscript, S. Perfetto (Vaccine Research Center, National Institutes of Health (NIH)) for flow cytometry advice, and J. Boyington and J. Whittle (Vaccine Research Center, NIH) for key discussions. This work was supported by the following awards to D.L.: a Harvard University Center for AIDS Research (CFAR) grant (P30 AI060354); a Broad-Ragon ENDHIV Catalytic grant; the William F. Milton Fund; and the Gilead Sciences Research Scholars Program in HIV. NR 48 TC 1 Z9 1 U1 6 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD FEB PY 2016 VL 11 IS 2 BP 193 EP 213 DI 10.1038/nprot.2016.009 PG 21 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA DC2YK UT WOS:000369084500001 PM 26741406 ER PT J AU Buchbinder, EI Hodi, FS AF Buchbinder, Elizabeth I. Hodi, F. Stephen TI Immune-checkpoint blockade - durable cancer control SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID UNTREATED MELANOMA; CTLA-4 BLOCKADE; IPILIMUMAB; NIVOLUMAB C1 [Buchbinder, Elizabeth I.; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM stephen_hodi@dfci.harvard.edu NR 10 TC 7 Z9 7 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD FEB PY 2016 VL 13 IS 2 BP 77 EP 78 DI 10.1038/nrclinonc.2015.237 PG 2 WC Oncology SC Oncology GA DC2GD UT WOS:000369034300006 PM 26787285 ER PT J AU Weir, GC AF Weir, Gordon C. TI Understanding secretion, ageing and death in beta cells SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Editorial Material AB The pancreatic islets of Langerhans have been intensively investigated for many years, largely because of their central role in the pathogenesis of type 1 and type 2 diabetes mellitus. Notable advances in 2015 related to glucose-stimulated insulin secretion in beta cells, beta-cell death and the rote of epigenetics in beta-cell heterogeneity. C1 [Weir, Gordon C.] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, 1 Joslin Pl, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu NR 5 TC 0 Z9 0 U1 4 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD FEB PY 2016 VL 12 IS 2 BP 72 EP 74 DI 10.1038/nrendo.2015.236 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DC3JM UT WOS:000369115600005 PM 26729035 ER PT J AU Lo, WK Goldberg, HJ Burakoff, R Feldman, N Chan, WW AF Lo, W. -K. Goldberg, H. J. Burakoff, R. Feldman, N. Chan, W. W. TI Increased proximal acid reflux is associated with early readmission following lung transplantation SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE acid reflux; GERD; impedance; lung transplant; post-transplant; readmission ID GASTROESOPHAGEAL-REFLUX; ALLOGRAFT INJURY; NORMAL VALUES; ASPIRATION; IMPEDANCE; DISEASE; BRONCHIOLITIS; REJECTION; THERAPY AB Background Gastroesophageal reflux disease has been associated with poor outcomes following lung transplantation. However, the association between pretransplant reflux and post-transplant readmission, an indicator of early clinical outcome, has not been previously assessed. Methods This was a retrospective cohort study of lung transplant recipients undergoing pretransplant multichannel intraluminal impedance and pH (MII-pH) study off acid suppression at a tertiary care center since 2007. Subjects with pretransplant fundoplication were excluded. Time to readmission was defined as duration from post-transplant discharge to next hospital admission for any reason. Subgroup analysis was performed to exclude elective readmissions. Time-to-event analysis was performed using Cox proportional hazards model, with appropriate censoring. Key Results Forty-three subjects (60% men, mean age: 57, median follow-up: 1.7 years) met inclusion criteria for the study. Patient demographics and pretransplant cardiopulmonary function were similar between readmission cohorts. Time to all-cause readmission was associated with increased distal acid episodes (HR: 3.15, p = 0.04) and proximal acid episodes (HR: 3.61, p = 0.008) on impedance, increased acid exposure on pH (HR: 2.22, p = 0.04), and elevated Demeester score (HR: 2.26, p = 0.03). When elective readmissions were excluded, early readmission remained significantly associated with increased proximal acid reflux episodes (HR: 2.49, p = 0.04). All findings were confirmed on Kaplan-Meier analysis. Conclusions & Inferences Elevated proximal acid reflux on pretransplant MII-pH testing was associated with early readmission following lung transplantation, even after excluding elective readmissions. Exposure to severe acid reflux has measurable effects on early postoperative outcomes such as readmission, and aggressive early antireflux therapy should be considered. C1 [Lo, W. -K.; Burakoff, R.; Feldman, N.; Chan, W. W.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA. [Lo, W. -K.] VA Boston Healthcare Syst, Dept Gastroenterol, Boston, MA USA. [Lo, W. -K.; Goldberg, H. J.; Burakoff, R.; Chan, W. W.] Harvard Univ, Sch Med, Boston, MA USA. [Goldberg, H. J.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. RP Chan, WW (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. EM wwchan@partners.org NR 21 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 28 IS 2 BP 251 EP 259 DI 10.1111/nmo.12720 PG 9 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA DB9EB UT WOS:000368818100011 PM 26568193 ER PT J AU Dijkink, S Fuentes, E Quraishi, SA Cropano, C Kaafarani, HMA Lee, J King, DR DeMoya, M Fagenholz, P Butler, K Velmahos, G Yeh, DD AF Dijkink, Suzan Fuentes, Eva Quraishi, Sadeq A. Cropano, Catrina Kaafarani, Haytham M. A. Lee, Jarone King, David R. DeMoya, Marc Fagenholz, Peter Butler, Kathryn Velmahos, George Yeh, Daniel Dante TI Nutrition in the Surgical Intensive Care Unit: The Cost of Starting Low and Ramping Up Rates SO NUTRITION IN CLINICAL PRACTICE LA English DT Article DE caloric deficit; feeding protocols; enteral nutrition; nutritional support; critical illness; intensive care units; clinical protocols ID CRITICALLY-ILL PATIENTS; PROTEIN-ENERGY PROVISION; ENTERAL NUTRITION; CALORIC-INTAKE; CLINICAL-OUTCOMES; RANDOMIZED-TRIAL; DELIVERY; INFECTIONS; MORTALITY; PROTOCOL AB Background: Calorie/protein deficit in the surgical intensive care unit (SICU) is associated with worse clinical outcomes. It is customary to initiate enteral nutrition (EN) at a low rate and increase to goal (RAMP-UP). Increasing evidence suggests that RAMP-UP may contribute to iatrogenic malnutrition. We sought to determine what proportion of total SICU calorie/protein deficit is attributable to RAMP-UP. Materials and Methods: This is a retrospective study of a prospectively collected registry of adult patients (N = 109) receiving at least 72 hours of EN in the SICU according to the RAMP-UP protocol (July 2012-June 2014). Subjects receiving only trophic feeds or with interrupted EN during RAMP-UP were excluded. Deficits were defined as the amount of prescribed calories/protein minus the actual amount received. RAMP-UP deficit was defined as the deficit between EN initiation and arrival at goal rate. Data included demographics, nutritional prescription/delivery, and outcomes. Results: EN was started at a median of 34.0 hours (interquartile range [IQR], 16.5-53.5) after ICU admission, with a mean duration of 8.7 +/- 4.3 days. The median total caloric deficit was 2185 kcal (249-4730), with 900 kcal (551-1562) attributable to RAMP-UP (41%). The protein deficit was 98.5 g (27.5-250.4), with 51.9 g (20.6-83.3) caused by RAMP-UP (53%). Conclusions: In SICU patients initiating EN, the RAMP-UP period accounted for 41% and 53% of the overall caloric and protein deficits, respectively. Starting EN immediately at goal rate may eliminate a significant proportion of macronutrient deficit in the SICU. C1 [Dijkink, Suzan; Fuentes, Eva; Cropano, Catrina; Kaafarani, Haytham M. A.; Lee, Jarone; King, David R.; DeMoya, Marc; Fagenholz, Peter; Butler, Kathryn; Velmahos, George; Yeh, Daniel Dante] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. [Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesiol, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. RP Dijkink, S (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM s.dijkink@lumc.nl FU Nestle FX Dr Daniel D. Yeh received a research grant from Nestle. The goal of this grant was to support research by Dr Yeh in general and not this research project specifically. Also no products of Nestle were discussed or alluded in this article, and Nestle had no influence on the results published. NR 26 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0884-5336 EI 1941-2452 J9 NUTR CLIN PRACT JI Nutr. Clin. Pract. PD FEB PY 2016 VL 31 IS 1 BP 86 EP 90 DI 10.1177/0884533615621047 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DC2LN UT WOS:000369048300011 PM 26673198 ER PT J AU Therkelsen, KE Pedley, A Rosenquist, KJ Hoffmann, U Massaro, JM Murabito, JM Fox, CS AF Therkelsen, Kate E. Pedley, Alison Rosenquist, Klara J. Hoffmann, Udo Massaro, Joseph M. Murabito, Joanne M. Fox, Caroline S. TI Adipose tissue attenuation as a marker of adipose tissue quality: Associations with six-year changes in body weight SO OBESITY LA English DT Article DE epidemiology; adipose tissue; population studies; obesity ID COMPUTED TOMOGRAPHIC ATTENUATION; INSULIN SENSITIVITY; ABDOMINAL FAT; OBESE INDIVIDUALS; CONTROLLED-TRIAL; RISK-FACTORS; FRAMINGHAM; EXERCISE; HEART; DIET AB ObjectiveWeight gain is associated with fat volume increases, but associations with fat quality are less well characterized The associations of weight change with visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volume and attenuation were investigated. MethodsComputed tomography abdominal scans were acquired on a Framingham Heart Study subset (N=836; 40.2% women; mean age 45.7years), a mean of 6.1years apart. Fat attenuation estimated fat quality. ResultsMean weight change was +2.0 (SD 6.8; IQR -0.7, 5.0)kg in women and +2.7 (SD 6.0; IQR -0.5, 5.4)kg in men. Per 2.5kg weight increase in women, VAT volume increased 126cm(3) (95% CI, 112-140, p<0.0001), SAT volume increased 258cm(3) (95% CI, 239-278, p<0.0001), and fat attenuation decreased (i.e., fat quality worsened) in VAT and SAT (p<0.0001). Increasing VAT volume was associated with decreasing fat attenuation even after accounting for weight change. Relative to weight-stable women (n=129), women who lost >2.5kg (n=58) had smaller SAT attenuation decreases (p<0.0001). Similar patterns were seen in men. ConclusionsWeight gain was associated with decreases in fat attenuation independent of VAT and SAT volume changes. These findings highlighted the associations of weight gain and worsening fat attenuation, suggesting fat attenuation may be dynamic. C1 [Therkelsen, Kate E.; Pedley, Alison; Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA USA. [Therkelsen, Kate E.; Pedley, Alison; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Therkelsen, Kate E.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Rosenquist, Klara J.] North Shore Phys Grp, Dept Endocrinol, Peabody, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, 75 Francis St, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Div Intramural Res, Framingham, MA USA.; Fox, CS (reprint author), NHLBI, Ctr Populat Studies, Framingham, MA USA.; Fox, CS (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Fox, CS (reprint author), Brigham & Womens Hosp, Div Endocrinol & Metab, 75 Francis St, Boston, MA 02115 USA. EM foxca@nhlbi.nih.gov FU [N01-HC-25195] FX The Framingham Heart Study of the National Heart, Lung, and Blood Institute is supported by contract N01-HC-25195. NR 30 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD FEB PY 2016 VL 24 IS 2 BP 499 EP 505 DI 10.1002/oby.21337 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA DC3SQ UT WOS:000369139500032 PM 26694629 ER PT J AU Guo, FJ Garvey, WT AF Guo, Fangjian Garvey, W. Timothy TI Cardiometabolic disease risk in metabolically healthy and unhealthy obesity: Stability of metabolic health status in adults SO OBESITY LA English DT Article ID BODY-MASS INDEX; TREATMENT PANEL-III; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; MYOCARDIAL-INFARCTION; NORMAL-WEIGHT; IMPACT; WOMEN; POPULATION; OVERWEIGHT AB ObjectiveTo assess the stability of metabolic status and body mass index (BMI) status and their relative contribution to risk of diabetes, cardiovascular events, and mortality. MethodsA total of 14,685 participants from the Atherosclerosis Risk in Communities Study and 4,990 from the Coronary Artery Risk Development in Young Adults Study were included. People with healthy obesity (HO) are defined as those meeting all three indices of blood pressure, blood glucose, and blood lipids. People with unhealthy obesity crossed the risk threshold for all three criteria. ResultsIn both healthy and unhealthy subgroups, risks for coronary heart disease (CHD), stroke, and mortality were comparable among BMI status during a mean 18.7-year follow-up. When compared with HO, hazard ratios were increased for diabetes (5.56, 95% confidence interval [CI] 4.12-7.48), CHD (5.60, 95% CI 3.14-9.98), stroke (4.84, 95% CI 2.13-10.97), and mortality (2.6, 95% CI 1.88-3.61) in people with unhealthy obesity. BMI only moderately increased the risks for diabetes among healthy subjects. In the Coronary Artery Risk Development in Young Adults Study over 20 years, 17.5% of lean subjects and 67.3% of overweight subjects at baseline developed obesity during follow-up. Despite rising BMI, metabolic status remained relatively stable. ConclusionsMetabolic status is relatively stable despite rising BMI. HO had lower risks for diabetes, CHD, stroke, and mortality than unhealthy subjects but increased diabetes risks than healthy lean people. Cardiometabolic risk factors confer much higher risk than obesity per se. 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 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr GRECC, Birmingham, AL USA. RP Guo, FJ (reprint author), Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.; Guo, FJ (reprint author), Univ Texas Med Branch, Ctr Interdisciplinary Res Womens Hlth, Galveston, TX 77555 USA.; Garvey, WT (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.; Garvey, WT (reprint author), Birmingham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr GRECC, Birmingham, AL USA. EM faguo@utmb.edu; garveyt@uab.edu OI Guo, Fangjian/0000-0003-3729-2724 FU Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) at the National Institutes of Health (NIH) [T32HD055163]; U.S. Department of Veterans Affairs, National Institutes of Health [DK-038765, DK-083562]; University of Alabama at Birmingham Diabetes Research Center [P60-DK079626] FX Dr. Guo is currently a postdoctoral fellow 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 National Institutes of Health (NIH). This study is supported by the Merit Review program of the U.S. Department of Veterans Affairs, National Institutes of Health (DK-038765 and DK-083562), and the University of Alabama at Birmingham Diabetes Research Center (P60-DK079626). NR 34 TC 9 Z9 9 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD FEB PY 2016 VL 24 IS 2 BP 516 EP 525 DI 10.1002/oby.21344 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA DC3SQ UT WOS:000369139500034 PM 26719125 ER PT J AU Yagi, Y Riedlinger, G Xu, X Nakamura, A Levy, B Iafrate, AJ Mino-Kenudson, M Klepeis, VE AF Yagi, Yukako Riedlinger, Gregory Xu, Xun Nakamura, Akira Levy, Bruce Iafrate, A. John Mino-Kenudson, Mari Klepeis, Veronica E. TI Development of a database system and image viewer to assist in the correlation of histopathologic features and digital image analysis with clinical and molecular genetic information SO PATHOLOGY INTERNATIONAL LA English DT Review DE database management system; genetic information; lung adenocarcinoma; image analysis; histopathology ID REARRANGED LUNG ADENOCARCINOMAS; EGFR MUTATIONS; PATHOLOGY AB Pathologists are required to integrate data from multiple sources when making a diagnosis. Furthermore, whole slide imaging (WSI) and next generation sequencing will escalate data size and complexity. Development of well-designed databases that can allow efficient navigation between multiple data types is necessary for both clinical and research purposes. We developed and evaluated an interactive, web-based database that integrates clinical, histologic, immunohistochemical and genetic information to aid in pathologic diagnosis and interpretation with nine lung adenocarcinoma cases. To minimize sectioning artifacts, representative blocks were serially sectioned using automated tissue sectioning (Kurabo Industries, Osaka Japan) and selected slides were stained by multiple techniques, (hematoxylin and eosin [H&E], immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH]). Slides were digitized by WSI scanners. An interactive relational database was designed based on a list of proposed fields covering a variety of clinical, pathologic and molecular parameters. By focusing on the three main tasks of 1.) efficient management of textual information, 2.) effective viewing of all varieties of stained whole slide images (WSI), and 3.) assistance in evaluating WSI with computer-aided diagnosis, this database prototype shows great promise for multi-modality research and diagnosis. C1 [Yagi, Yukako; Riedlinger, Gregory; Levy, Bruce; Iafrate, A. John; Mino-Kenudson, Mari; Klepeis, Veronica E.] Harvard Univ, Sch Med, 101 Merrimac St,Suite 820, Boston, MA 02114 USA. [Yagi, Yukako; Riedlinger, Gregory; Levy, Bruce; Iafrate, A. John; Mino-Kenudson, Mari; Klepeis, Veronica E.] Massachusetts Gen Hosp, 101 Merrimac St,Suite 820, Boston, MA 02114 USA. [Xu, Xun; Nakamura, Akira] Sony Elect Inc, San Jose, CA USA. [Riedlinger, Gregory] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Levy, Bruce] Univ Illinois, Chicago, IL USA. RP Yagi, Y (reprint author), Harvard Univ, Sch Med, 101 Merrimac St,Suite 820, Boston, MA 02114 USA.; Yagi, Y (reprint author), Massachusetts Gen Hosp, 101 Merrimac St,Suite 820, Boston, MA 02114 USA. EM yyagi@mgh.harvard.edu FU Sony Corporation, Tokyo, Japan FX This project was supported by Sony Corporation, Tokyo, Japan. NR 21 TC 1 Z9 1 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5463 EI 1440-1827 J9 PATHOL INT JI Pathol. Int. PD FEB PY 2016 VL 66 IS 2 BP 63 EP 74 DI 10.1111/pin.12382 PG 12 WC Pathology SC Pathology GA DC3VG UT WOS:000369146400002 PM 26778830 ER PT J AU Korppi, M Kivisto, J Koponen, P Lehtinen, P Remes, S Piippo-Savolainen, E Piedra, PA Espinola, JA Camargo, CA Jartti, T AF Korppi, Matti Kivisto, Juho Koponen, Petri Lehtinen, Pasi Remes, Sami Piippo-Savolainen, Eija Piedra, Pedro A. Espinola, Janice A. Camargo, Carlos A., Jr. Jartti, Tuomas TI ABSENCE OF BORDETELLA PERTUSSIS AMONG INFANTS HOSPITALIZED FOR BRONCHIOLITIS IN FINLAND, 2008-2010 SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Bordetella pertussis; bronchiolitis; infant; polymerase chain reaction; respiratory syncytial virus ID LENGTH-OF-STAY; CHILDREN; ETIOLOGY; SEASON AB In 169 Finnish infants hospitalized for bronchiolitis at age <6 months in 2008-2010, nasopharyngeal aspirates were tested by polymerase chain reaction for Bordetella pertussis and 16 viruses. Respiratory viruses were detected in 89% (71% with respiratory syncytial virus), but no infant had B. pertussis. The latter finding may reflect a positive effect from the broadening of the Finnish pertussis vaccination program in 2005. C1 [Korppi, Matti; Kivisto, Juho; Koponen, Petri] Tampere Univ, Ctr Child Hlth Res, FIN-33101 Tampere, Finland. [Korppi, Matti; Kivisto, Juho; Koponen, Petri] Tampere Univ Hosp, Tampere, Finland. [Lehtinen, Pasi; Jartti, Tuomas] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. [Remes, Sami; Piippo-Savolainen, Eija] Kuopio Univ Hosp, Dept Pediat, SF-70210 Kuopio, Finland. [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. [Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Korppi, M (reprint author), Tampere Univ, Ctr Child Hlth Res, FIN-33101 Tampere, Finland.; Korppi, M (reprint author), 33014 Tampere Univ, Univ Hosp, Tampere, Finland. EM matti.korppi@uta.fi FU Academy of Finland, Helsinki, Finland [132595, 114034]; Finnish Medical Foundation, Helsinki, Finland FX T.J. was supported by the Academy of Finland (grant numbers 132595 and 114034) and the Finnish Medical Foundation, both in Helsinki, Finland. The other authors have no conflicts of interest to disclose. NR 11 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 2016 VL 35 IS 2 BP 219 EP 221 DI 10.1097/INF.0000000000000973 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA DB7WL UT WOS:000368727500022 PM 26551447 ER PT J AU Golier, JA Caramanica, K Michaelides, AC Makotkine, I Schmeidler, J Harvey, PD Yehuda, R AF Golier, Julia A. Caramanica, Kimberly Michaelides, Andreas C. Makotkine, Iouri Schmeidler, James Harvey, Philip D. Yehuda, Rachel TI A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Gulf War; Mifepristone; CMI; Dexamethasone; ACTH; Cortisol; Verbal learning ID POSTTRAUMATIC-STRESS-DISORDER; OPEN-LABEL TRIAL; PSYCHOTIC DEPRESSION; COGNITIVE DYSFUNCTION; ALZHEIMERS-DISEASE; HIPPOCAMPAL; MEMORY; DEXAMETHASONE; NEUROGENESIS; RU-486 AB No pharmacological treatments have been demonstrated to effectively treat chronic multisymptom illness (CMI) in Gulf War veterans (GWV). This study assessed the effect of the glucocorticoid receptor antagonist mifepristone in GWV with CMI. A randomized, double-blind, cross-over trial of mifepristone, with two six-week treatment phases separated by a one-month washout period, was conducted at a Veterans Affairs (VA) hospital between 2008 and 2011. Participants were randomized to receive either 200 mg of mifepristone per day or matched placebo first. The primary clinical outcome measure was change in self-reported physical health. Neurocognitive functioning and self-reported measures of depression, PTSD, and fatigue were secondary outcomes. Sixty-five participants enrolled, of whom 36 were randomized and 32 (mean age, 49.1 (7.2) years) completed the study. Physical and mental health status and neurocognitive functioning were poor at baseline. Mifepristone treatment was not associated with improvement in self-reported physical health (p = 0.838) or in other self-reported measures of mental health. Mifepristone treatment was significantly associated with improvements in verbal learning (p = 0.008, d = 0.508), in the absence of improvement in other cognitive measures (working memory (p = 0.914), visual learning (p = 0.643) and a global composite measure (p = 0.937). Baseline morning cortisol levels and lysozyme IC50-DEX, a measure of peripheral glucocorticoid sensitivity, displayed a significant relationship with endpoint verbal learning scores (p = 0.012 and p = 0.007, respectively). The magnitude of cortisol change during treatment mediated the improvement in verbal learning. This study was negative for the primary and secondary clinical outcomes. However, the data suggest a moderate dose of mifepristone may have circumscribed cognitive-enhancing effects in CMI. Further study is warranted to determine whether and through which mechanisms mifepristone treatment can yield clinically meaningful improvement in cognitive function in CMI or other neuropsychiatric conditions associated with HPA axis dysregulation. (C) Published by Elsevier Ltd. C1 [Golier, Julia A.; Caramanica, Kimberly; Michaelides, Andreas C.; Makotkine, Iouri; Yehuda, Rachel] James J Peters VA Med Ctr, OOMH 526,130 West Kingsbridge Rd, Bronx, NY 10468 USA. [Golier, Julia A.; Makotkine, Iouri; Schmeidler, James; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, 1428 Madison Ave, New York, NY 10029 USA. [Harvey, Philip D.] Univ Miami, Miller Sch Med, 1600 NW 10th Ave 1140, Miami, FL 33136 USA. RP Golier, JA (reprint author), James J Peters VA Med Ctr, OOMH 526,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM julia.golier@va.gov FU Department of Defense (DoD) FX This study is registered with ClinicalTrials.gov (NCT00691067) and was solely funded by the Department of Defense (DoD). The DoD did not influence any aspects of the study design or manuscript preparation. The authors declare no conflicts of interests. The authors also acknowledge the assistance of Ahmed El-Razi, B.A. in the revising of the manuscript. NR 44 TC 2 Z9 2 U1 4 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD FEB PY 2016 VL 64 BP 22 EP 30 DI 10.1016/j.psyneuen.2015.11.001 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA DB9WF UT WOS:000368867700003 PM 26600007 ER PT J AU Kline, CE Reboussin, DM Foster, GD Rice, TB Strotmeyer, ES Jakicic, JM Millman, RP Pi-Sunyer, X Newman, AB Wadden, TA Zammit, G Kuna, ST AF Kline, Christopher E. Reboussin, David M. Foster, Gary D. Rice, Thomas B. Strotmeyer, Elsa S. Jakicic, John M. Millman, Richard P. Pi-Sunyer, Xavier Newman, Anne B. Wadden, Thomas A. Zammit, Gary Kuna, Samuel T. CA Look AHEAD Res Grp TI The Effect of Changes in Cardiorespiratory Fitness and Weight on Obstructive Sleep Apnea Severity in Overweight Adults with Type 2 Diabetes SO SLEEP LA English DT Article DE apnea-hypopnea index; cardiorespiratory fitness; obstructive sleep apnea; physical activity; weight loss ID LIFE-STYLE INTERVENTION; CARDIOVASCULAR-DISEASE RISK; RANDOMIZED CONTROLLED-TRIAL; POSITIVE AIRWAY PRESSURE; HEART-RATE RECOVERY; ALL-CAUSE MORTALITY; PHYSICAL-ACTIVITY; OBESE-PATIENTS; FOLLOW-UP; METABOLIC SYNDROME AB Study Objectives: To examine the effect of changes in cardiorespiratory fitness on obstructive sleep apnea (OSA) severity prior to and following adjustment for changes in weight over the course of a 4-y weight loss intervention. Methods: As secondary analyses of a randomized controlled trial, 263 overweight/obese adults with type 2 diabetes and OSA participated in an intensive lifestyle intervention or education control condition. Measures of OSA severity, cardiorespiratory fitness, and body weight were obtained at baseline, year 1, and year 4. Change in the apnea-hypopnea index (AHI) served as the primary outcome. The percentage change in fitness (submaximal metabolic equivalents [METs]) and change in weight (kg) were the primary independent variables. Primary analyses collapsed intervention conditions with statistical adjustment for treatment group and baseline METs, weight, and AHI among other relevant covariates. Results: At baseline, greater METs were associated with lower AHI (B [SE] = -1.48 [0.71], P = 0.038), but this relationship no longer existed (B [SE] = -0.24 [0.73], P = 0.75) after adjustment for weight (B [SE] = 0.31 [0.07], P < 0.0001). Fitness significantly increased at year 1 (+16.53 +/- 28.71% relative to baseline), but returned to near-baseline levels by year 4 (+1.81 +/- 24.48%). In mixed-model analyses of AHI change over time without consideration of weight change, increased fitness at year 1 (B [SE] = -0.15 [0.04], P < 0.0001), but not at year 4 (B [SE] = 0.04 [0.05], P = 0.48), was associated with AHI reduction. However, with weight change in the model, greater weight loss was associated with AHI reduction at years 1 and 4 (B [SE] = 0.81 [0.16] and 0.60 [0.16], both P < 0.0001), rendering the association between fitness and AHI change at year 1 nonsignificant (B [SE] = -0.04 [0.04], P = 0.31). Conclusions: Among overweight/obese adults with type 2 diabetes, fitness change did not influence OSA severity change when weight change was taken into account. C1 [Kline, Christopher E.; Rice, Thomas B.; Strotmeyer, Elsa S.; Jakicic, John M.; Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Reboussin, David M.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Foster, Gary D.] Temple Univ, Philadelphia, PA 19122 USA. [Foster, Gary D.] Weight Watchers Int, New York, NY USA. [Millman, Richard P.] Brown Univ, Providence, RI 02912 USA. [Pi-Sunyer, Xavier] Columbia Univ, New York, NY USA. [Wadden, Thomas A.; Kuna, Samuel T.] Univ Penn, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Kline, CE (reprint author), Univ Pittsburgh, Dept Hlth & Phys Act, 32 Oak Hill Court,Room 227, Pittsburgh, PA 15261 USA. EM chriskline@pitt.edu RI Newman, Anne B./C-6408-2013; OI Newman, Anne B./0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036 FU Abbott; Abbvie; Actelion; Ancile; Apnex; Arena; Aptalis; Astra-Zeneca; Aventis; Banyu; Biomarin; BMS; Catalyst; Celgene; Cephalon; CHDI; Edgemont; Elan; Epix; Eisai; Elminda; Evotec; Forest; Fresca; Galderma; Genentech; Gilead; Glaxo Smith Kline; H. Lundbeck A/S; Janssen; Jazz; Johnson Johnson; King; Merck and Co.; National Institutes of Health (NIH); Neurim; Neurocrine Biosciences; Naurex; Neurogen; Novo Nordisk; Organon; Orphan Medical; Otsuka; Pfizer; Predix; Respironics; Roxane; Saladax; Sanofi-Aventis; Sanofi-Synthelabo; Schering-Plough; Sepracor; Sunovion; Shire; Somaxon; Takeda; Takeda Pharmaceuticals North America; Targacept; Teva; Thymon; Transcept; UCB; USWorldmeds; Pharma; Ultragenyx; Vanda; Wyeth-Ayerst Research; Orexigen; Nutrisystem; Weight Watchers; Jawbone; [HL070301]; [DK60426]; [DK56992]; [DK057135]; [HL118318] FX This was not an industry supported study. Financial support was provided by HL070301, DK60426, DK56992, DK057135, HL118318. Dr. Zammit is a consultant for Acorda, Actelion, Alexza, Arena, Aventis, Biovail, Boehringer-Ingelheim, Cephalon, Elan, Eli Lilly, Evotec, Forest, Glaxo Smith Kline, Jazz, King Pharmaceuticals, Ligand, McNeil, Merck, Neurocrine Biosciences, Organon, Pfizer, Purdue, Renovis, Sanofi-Aventis, Select Comfort, Sepracor, Shire, Somnus, Takeda Pharmaceuticals, Vela, and Wyeth; has grant support from Abbott, Abbvie, Actelion, Ancile, Apnex, Arena, Aptalis, Astra-Zeneca, Aventis, Banyu, Biomarin, BMS, Catalyst, Celgene, Cephalon, CHDI, Edgemont, Elan, Epix, Eisai, Elminda, Evotec, Forest, Fresca, Galderma, Genentech, Gilead, Glaxo Smith Kline, Gilead, H. Lundbeck A/S, Janssen, Jazz, Johnson & Johnson, King, Merck and Co., National Institutes of Health (NIH), Neurim, Neurocrine Biosciences, Naurex, Neurim, Neurogen, Novo Nordisk, Organon, Orphan Medical, Otsuka, Pfizer, Predix, Respironics, Roxane, Saladax, Sanofi-Aventis, Sanofi-Synthelabo, Schering-Plough, Sepracor, Sunovion, Shire, Somaxon, Takeda, Takeda Pharmaceuticals North America, Targacept, Teva, Thymon, Transcept, UCB, USWorldmeds, Pharma, Ultragenyx, Predix, Vanda, and Wyeth-Ayerst Research; and has received honoraria from King Pharmaceuticals, McNeil, Merck, Neurocrine Biosciences, Sanofi-Aventis, Sanofi-Synthelabo, Sepracor, Takeda Pharmaceuticals, Vela Pharmaceuticals, and Wyeth-Ayerst Research. Dr. Wadden serves on Scientific Advisory Boards for Orexigen, Novo Nordisk, Nutrisystem, and Weight Watchers and has received grant support, on behalf of the University of Pennsylvania, from Orexigen, Novo Nordisk, Nutrisystem, and Weight Watchers. Dr. Jakicic is a member of Weight Watchers International Scientific Advisory Board and has served as the Principal Investigator on a research grant received from Jawbone that was awarded to the University of Pittsburgh. Dr. Foster is the Chief Scientific Officer for Weight Watchers International. The other authors have indicated no financial conflicts of interest. The work was performed at: Brown University, Providence, RI; St. Luke's-Roosevelt Hospital/Clinilabs, New York, NY; Temple University, Philadelphia, PA; University of Pennsylvania, Philadelphia, PA; and University of Pittsburgh, Pittsburgh, PA. NR 62 TC 1 Z9 1 U1 2 U2 9 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD FEB 1 PY 2016 VL 39 IS 2 BP 317 EP 325 DI 10.5665/sleep.5436 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DC0WH UT WOS:000368938100008 PM 26446118 ER PT J AU Ioannou, GN AF Ioannou, George N. TI The Role of Cholesterol in the Pathogenesis of NASH SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID FATTY LIVER-DISEASE; HEPATIC STELLATE CELLS; LOW-DENSITY-LIPOPROTEIN; ENDOPLASMIC-RETICULUM STRESS; NONALCOHOLIC STEATOHEPATITIS; LIPID DROPLETS; INSULIN-RESISTANCE; OXIDIZED LDL; HEPATOCELLULAR-CARCINOMA; CARDIOVASCULAR-DISEASE AB Lipotoxicity drives the development of progressive hepatic inflammation and fibrosis in a subgroup of patients with nonalcoholic fatty liver disease (NAFLD), causing nonalcoholic steatohepatitis (NASH) and even progression to cirrhosis and hepatocellular carcinoma (HCC). While the underlying molecular mechanisms responsible for the development of inflammation and fibrosis that characterize progressive NASH remain unclear, emerging evidence now suggests that hepatic free cholesterol (FC) is a major lipotoxic molecule critical in the development of experimental and human NASH. In this review, we examine the effects of excess FC in hepatocytes, Kupffer cells (KCs), and hepatic stellate cells (HSCs), and the subcellular mechanisms by which excess FC can induce cellular toxicity or proinflammatory and profibrotic effects in these cells. C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA USA. [Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA USA.; Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA USA.; Ioannou, GN (reprint author), Univ Washington, Seattle, WA 98195 USA. EM georgei@medicine.washington.edu NR 99 TC 8 Z9 9 U1 7 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD FEB PY 2016 VL 27 IS 2 BP 84 EP 95 DI 10.1016/j.tem.2015.11.008 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DC1DE UT WOS:000368956200003 PM 26703097 ER PT J AU Kramer, H Rosas, SE Matsushita, K AF Kramer, Holly Rosas, Sylvia E. Matsushita, Kunihiro TI Beef Tea, Vitality, Creatinine, and the Estimated GFR SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID GLOMERULAR-FILTRATION-RATE; CYSTATIN-C; KIDNEY-FUNCTION; SERUM; RISK; POPULATION C1 [Kramer, Holly] Loyola Univ Chicago, Maywood, IL 60153 USA. [Rosas, Sylvia E.] Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. [Matsushita, Kunihiro] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Kramer, H (reprint author), Loyola Univ Chicago, Dept Publ Hlth Sci, 2160 First Ave, Maywood, IL 60153 USA. EM hkramer@luc.edu NR 15 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 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2016 VL 67 IS 2 BP 169 EP 172 DI 10.1053/j.ajkd.2015.11.001 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA DB3NQ UT WOS:000368418800005 PM 26802326 ER PT J AU Boyce, R Mitton, J Chu, J Finn, K AF Boyce, Ross Mitton, Julian Chu, Jacqueline Finn, Kathleen TI South Sudan to Martha's Vineyard: Malaria SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID HUMAN BABESIOSIS; UNITED-STATES; SURVEILLANCE C1 [Boyce, Ross; Mitton, Julian; Finn, Kathleen] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chu, Jacqueline] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Boyce, R (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GB 740, Boston, MA 02114 USA. EM roboyce@gmail.com OI Boyce, Ross/0000-0002-9489-6324 NR 9 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD FEB PY 2016 VL 129 IS 2 BP 163 EP 166 DI 10.1016/j.amjmed.2015.08.030 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DB2MG UT WOS:000368342300032 PM 26394268 ER PT J AU Waks, JW Steinhaus, DA Shvilkin, A Kramer, DB AF Waks, Jonathan W. Steinhaus, Daniel A. Shvilkin, Alexei Kramer, Daniel B. TI Post-pacemaker T-wave Inversions: Cardiac Memory SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID ABNORMALITIES C1 Harvard Univ, Sch Med, Harvard Thorndike Electrophys Inst, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Arrhythmia Serv,Div Cardiovasc Med,Dept Med, Boston, MA 02215 USA. RP Kramer, DB (reprint author), Beth Israel Deaconess Med Ctr, 185 Pilgrim Rd,Baker 4, Boston, MA 02215 USA. EM dkramer@bidmc.harvard.edu OI Shvilkin, Alexei/0000-0003-3662-9938 FU NIA NIH HHS [K23 AG045963, K23AG045963] NR 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD FEB PY 2016 VL 129 IS 2 BP 170 EP 172 DI 10.1016/j.amjmed.2015.09.001 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DB2MG UT WOS:000368342300034 PM 26440583 ER PT J AU Kearney, DJ Simpson, TL Malte, CA Felleman, B Martinez, ME Hunt, SC AF Kearney, David J. Simpson, Tracy L. Malte, Carol A. Felleman, Benjamin Martinez, Michelle E. Hunt, Stephen C. TI Mindfulness-based Stress Reduction in Addition to Usual Care Is Associated with Improvements in Pain, Fatigue, and Cognitive Failures Among Veterans with Gulf War Illness SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Complementary and alternative medicine; Gulf War illness; Mindfulness; Veterans ID QUALITY-OF-LIFE; HEALTH-STATUS; THEORETICAL CONSIDERATIONS; ALTERNATIVE MEDICINE; PHYSICAL SYMPTOMS; FOLLOW-UP; THERAPY; QUESTIONNAIRE; DEPRESSION; DISORDER AB BACKGROUND: Many Gulf War I veterans report ongoing negative health consequences. The constellation of pain, fatigue, and concentration/memory disturbances is referred to as "Gulf War illness." Prior research suggests that mindfulness-based stress reduction may be beneficial for these symptoms, but mindfulness-based stress reduction has not been studied for veterans with Gulf War illness. The objective of this trial was to conduct a pilot study of mindfulness-based stress reduction for veterans with Gulf War illness. METHODS: Veterans (N = 55) with Gulf War illness were randomly assigned to treatment as usual plus mindfulness-based stress reduction or treatment as usual only. Mindfulness-based stress reduction was delivered in 8 weekly 2.5-hour sessions plus a single 7-hour weekend session. Pain, fatigue, and cognitive failures were the primary outcomes, assessed at baseline, after mindfulness-based stress reduction, and 6 months follow-up. Secondary outcomes included symptoms of posttraumatic stress disorder and depression. RESULTS: In intention-to-treat analyses, at 6-month follow-up, veterans randomized to mindfulness-based stress reduction plus treatment as usual reported greater reductions in pain (f = 0.33; P = .049), fatigue (f = 0.32; P = .027), and cognitive failures (f = 0.40; P < .001). Depressive symptoms showed a greater decline after mindfulness-based stress reduction (f = 0.22; P = .050) and at 6 months (f = 0.27; P = .031) relative to treatment as usual only. Veterans with posttraumatic stress disorder at baseline randomized to mindfulness-based stress reduction plus treatment as usual experienced significantly greater reductions in symptoms of posttraumatic stress disorder after mindfulness-based stress reduction (f = 0.44; P = .005) but not at 6 months follow-up (f = 0.31; P = .082). CONCLUSIONS: Mindfulness-based stress reduction in addition to treatment as usual is associated with significant improvements in self-reported symptoms of Gulf War illness, including pain, fatigue, cognitive failures, and depression. Published by Elsevier Inc. C1 [Kearney, David J.; Hunt, Stephen C.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Kearney, David J.; Hunt, Stephen C.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Simpson, Tracy L.; Malte, Carol A.] VA Puget Sound Hlth Care Syst, Ctr Excellence Substance Abuse Treatment & Educ C, Seattle, WA USA. [Simpson, Tracy L.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Felleman, Benjamin; Martinez, Michelle E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Kearney, DJ (reprint author), Seattle VAMC 111GI,1660 S Columbian Way, Seattle, WA 98108 USA. EM david.kearney@va.gov FU VA Office of Research and Development [5I01CX000313-02] FX This trial was funded by a grant from the VA Office of Research and Development (5I01CX000313-02). NR 70 TC 1 Z9 1 U1 6 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD FEB PY 2016 VL 129 IS 2 BP 204 EP 214 DI 10.1016/j.amjmed.2015.09.015 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DB2MG UT WOS:000368342300039 PM 26519614 ER PT J AU Matioc, AA AF Matioc, Adrian A. TI An Anesthesiologist's Perspective on the History of Basic Airway Management The "Preanesthetic" Era-1700 to 1846 SO ANESTHESIOLOGY LA English DT Article ID RESUSCITATION AB Basic airway management modern history starts in the early 18th century in the context of resuscitation of the apparently dead. History saw the rise and fall of the mouth-to-mouth and then of the instrumental positive-pressure ventilation generated by bellows. Pulmonary ventilation had a secondary role to external and internal organ stimulation in resuscitation of the apparently dead. Airway access for the extraglottic technique was to the victim's nose. The bellows-to-nose technique was the basic airway management technique applicable by both medical and nonmedical personnel. Although the techniques had been described at the time, very few physicians practiced glottic (intubation) and subglottic (tracheotomy) techniques. Before the anesthetic era, positive-pressure ventilation was discredited and replaced by manual negative-pressure techniques. In the middle of the 19th century, physicians who would soon administer anesthetic gases were unfamiliar with the positive-pressure ventilation concept. C1 [Matioc, Adrian A.] Univ Wisconsin, Dept Anesthesiol, Sch Med & Publ Hlth, Madison, WI USA. [Matioc, Adrian A.] William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room A8030, Madison, WI 53705 USA. RP Matioc, AA (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room A8030, Madison, WI 53705 USA. EM aamatioc@wisc.edu FU Paul M. Wood Fellowship at the Wood Library-Museum of Anesthesiology, Schaumburg, Illinois FX Support was provided by departmental sources and by a 2013 Paul M. Wood Fellowship at the Wood Library-Museum of Anesthesiology, Schaumburg, Illinois, awarded in the author name for this topic. NR 61 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 2016 VL 124 IS 2 BP 301 EP 311 DI 10.1097/ALN.0000000000000955 PG 11 WC Anesthesiology SC Anesthesiology GA DB5FP UT WOS:000368540300008 PM 26580835 ER PT J AU Ladha, KS Patorno, E Liu, J Bateman, BT AF Ladha, Karim S. Patorno, Elisabetta Liu, Jun Bateman, Brian T. TI Impact of Perioperative Epidural Placement on Postdischarge Opioid Use in Patients Undergoing Abdominal Surgery SO ANESTHESIOLOGY LA English DT Article ID TERM POSTTHORACOTOMY PAIN; PREVENTIVE ANALGESIA; POSTSURGICAL PAIN; RISK-FACTORS; COHORT; METAANALYSIS; ANESTHESIA; MANAGEMENT; SCORE AB Background: Opioids play a crucial role in providing analgesia throughout the perioperative period; however, patients may become persistent users of these medications months after surgery. Epidurals have been posited to prevent the development of persistent pain, but there are little data on the effect of epidurals on persistent opioid use. Methods: This study was conducted using a claims database of a large, nationwide commercial health insurer. Opioid-naive patients who underwent open abdominal surgery from January 2004 to December 2013 were included in the study. Propensity scores for epidural placement were calculated accounting for demographic characteristics, resource utilization, and comorbid conditions (including medical, psychiatric, and pain conditions). Time-to-event analysis was used with the primary outcome defined as 30 days without filling an opioid prescription after discharge. In addition, total morphine equivalents dispensed within 90 days of discharge were also calculated for each patient. Results: A total of 6,432 patients were included in the final propensity score-matched cohort. The Cox proportional hazards ratio was 0.96 (95% CI, 0.91 to 1.01; P = 0.0910) for the relation between epidural placement and time till a 30-day gap without filling an opioid prescription. There was no difference in the total morphine equivalents dispensed within 90 days of discharge between the groups (P = 0.7670). Conclusions: Epidural placement was not protective against persistent opioid use in a large cohort of opioid-naive patients undergoing abdominal surgery. This finding does not detract from the other potential benefits of epidural placement. More research is needed to understand the mechanism of persistent opioid use after surgery and its prevention. C1 [Ladha, Karim S.; Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA. [Ladha, Karim S.] Toronto Gen Hosp, Dept Anesthesia, Toronto, ON, Canada. [Ladha, Karim S.] Univ Toronto, Toronto, ON, Canada. [Patorno, Elisabetta; Liu, Jun; Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA. RP Ladha, KS (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM karim.ladha@post.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (Bethesda, Maryland) [K08HD075831] FX Dr. Bateman is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (Bethesda, Maryland) under award number K08HD075831. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 28 TC 3 Z9 3 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 FEB PY 2016 VL 124 IS 2 BP 396 EP 403 DI 10.1097/ALN.0000000000000952 PG 8 WC Anesthesiology SC Anesthesiology GA DB5FP UT WOS:000368540300017 PM 26575145 ER PT J AU Lee, SM Takemoto, S Wallace, AW AF Lee, Susan M. Takemoto, Steven Wallace, Arthur W. TI Early Postoperative Withholding Angiotensin Receptor Blockers and 30-day Mortality after Noncardiac Surgery Reply SO ANESTHESIOLOGY LA English DT Letter ID SYSTEMS C1 [Lee, Susan M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Lee, SM (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. EM susan.lee5@va.gov NR 5 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 FEB PY 2016 VL 124 IS 2 BP 513 EP 514 DI 10.1097/ALN.0000000000000965 PG 2 WC Anesthesiology SC Anesthesiology GA DB5FP UT WOS:000368540300032 PM 26785436 ER PT J AU Lee, CH Verma, P Lee, J Klaustermeyer, WB AF Lee, Christina H. Verma, Prashant Lee, Joyce Klaustermeyer, William B. TI Cost analysis of asthma maintenance medications in a veteran population SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter C1 [Lee, Christina H.; Verma, Prashant; Lee, Joyce; Klaustermeyer, William B.] Univ Calif Los Angeles, Dept Med, Div Allergy & Immunol, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RP Klaustermeyer, WB (reprint author), Univ Calif Los Angeles, Dept Med, Div Allergy & Immunol, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. EM william.klaustermeyer@va.gov NR 8 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 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD FEB PY 2016 VL 116 IS 2 BP 165 EP 166 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA DB5SD UT WOS:000368573000016 PM 26702545 ER PT J AU Cairns, J Ingle, J Dudenkov, T Kalari, K Buzdar, A Kubo, M Robson, M Ellis, M Goss, P Shepherd, L Weinshilboum, R Wang, L AF Cairns, J. Ingle, J. Dudenkov, T. Kalari, K. Buzdar, A. Kubo, M. Robson, M. Ellis, M. Goss, P. Shepherd, L. Weinshilboum, R. Wang, L. TI AROMATASE INHIBITOR-INDUCED HORMONE LEVEL CHANGE ASSOCIATED WITH CSMD1 SNP AND ANDROSTENEDIONE-DEPENDENT VARIATION IN AROMATASE EXPRESSION. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 08-12, 2016 CL San Diego, CA SP Amer Soc Clin Pharmacol & Therapeut C1 [Cairns, J.; Ingle, J.; Dudenkov, T.; Kalari, K.; Weinshilboum, R.; Wang, L.] Mayo Clin, Rochester, MN USA. [Buzdar, A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kubo, M.] RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan. [Robson, M.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Ellis, M.] Baylor Canc Ctr, Houston, TX USA. [Goss, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shepherd, L.] NCIC Clin Trials Grp, Kingston, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2016 VL 99 SU 1 MA PII-038 BP S84 EP S85 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DB7JZ UT WOS:000368692600303 ER PT J AU Gomeni, R Bressolle, F Spencer, TJ Faraone, SV AF Gomeni, R. Bressolle, F. Spencer, T. J. Faraone, S. V. TI USE OF A CLINICAL RESPONSE INDEX DERIVED FROM A PK/PD MODEL TO ESTIMATE THE OPTIMAL IN VIVO RELEASE RATE OF EXTENDED RELEASE FORMULATIONS OF MPH. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 08-12, 2016 CL San Diego, CA SP Amer Soc Clin Pharmacol & Therapeut C1 [Gomeni, R.; Bressolle, F.] Pharmacometrica, La Fouillade, France. [Spencer, T. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faraone, S. V.] SUNY Upstate Med Univ, Syracuse, NY 13210 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 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2016 VL 99 SU 1 MA E-004 BP S22 EP S22 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DB7JZ UT WOS:000368692600066 ER PT J AU Gomeni, R Bressolle, F Spencer, TJ Faraone, SV AF Gomeni, R. Bressolle, F. Spencer, T. J. Faraone, S. V. TI OPTIMAL STUDY DESIGN TO EVALUATE THE CLINICAL RESPONSE OF EXTENDED RELEASE FORMULATIONS OF METHYLPHENIDATE (MPH)IN A PEDIATRIC POPULATION. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 08-12, 2016 CL San Diego, CA SP Amer Soc Clin Pharmacol & Therapeut C1 [Gomeni, R.; Bressolle, F.] Pharmacometrica, La Fouillade, France. [Spencer, T. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faraone, S. V.] SUNY Upstate Med Univ, Syracuse, NY 13210 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 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2016 VL 99 SU 1 MA E-005 BP S22 EP S22 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DB7JZ UT WOS:000368692600067 ER PT J AU Gomeni, R Bressolle, F Spencer, TJ Faraone, SV AF Gomeni, R. Bressolle, F. Spencer, T. J. Faraone, S. V. TI META-ANALYTIC APPROACH TO EVALUATE ALTERNATIVE MODELS FOR CHARACTERIZING THE PK PROFILES OF EXTENDED RELEASE FORMULATIONS OF MPH. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 08-12, 2016 CL San Diego, CA SP Amer Soc Clin Pharmacol & Therapeut C1 [Gomeni, R.; Bressolle, F.] Pharmacometrica, La Fouillade, France. [Spencer, T. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faraone, S. V.] SUNY Upstate Med Univ, Syracuse, NY 13210 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 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2016 VL 99 SU 1 MA E-003 BP S21 EP S21 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DB7JZ UT WOS:000368692600065 ER PT J AU Morrissey, K Vora, B Zhu, R Apt, D Olivero, A Ware, J Mueller, L Cloughesy, T Gerstner, E Rodon, J Wen, P Salphati, L AF Morrissey, K. Vora, B. Zhu, R. Apt, D. Olivero, A. Ware, J. Mueller, L. Cloughesy, T. Gerstner, E. Rodon, J. Wen, P. Salphati, L. TI CLINICAL PHARMACOKINETICS AND BRAIN PENETRATION OF GDC-0084, AN ORAL PI3K/mTOR INHIBITOR, IN PATIENTS WITH HIGH-GRADE GLIOMA. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 08-12, 2016 CL San Diego, CA SP Amer Soc Clin Pharmacol & Therapeut C1 [Morrissey, K.; Vora, B.; Zhu, R.; Apt, D.; Olivero, A.; Ware, J.; Mueller, L.; Salphati, L.] Genentech Inc, San Francisco, CA 94080 USA. [Cloughesy, T.] Univ Calif Los Angeles, Los Angeles, CA USA. [Gerstner, E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Rodon, J.] Vall dHebron Inst Oncol, Barcelona, Spain. [Wen, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2016 VL 99 SU 1 MA PII-045 BP S86 EP S87 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DB7JZ UT WOS:000368692600310 ER PT J AU Pirrone, M Fisher, D Chipman, D Imber, DAE Corona, J Mietto, C Kacmarek, RM Berra, L AF Pirrone, Massimiliano Fisher, Daniel Chipman, Daniel Imber, David A. E. Corona, Javier Mietto, Cristina Kacmarek, Robert M. Berra, Lorenzo TI Recruitment Maneuvers and Positive End-Expiratory Pressure Titration in Morbidly Obese ICU Patients SO CRITICAL CARE MEDICINE LA English DT Article DE lung compliance; mechanical ventilation; obesity; positive end-expiratory pressure; pulmonary gas exchange; respiratory mechanics ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; BODY-MASS INDEX; MECHANICAL VENTILATION; NITROGEN WASHOUT/WASHIN; ANESTHESIA; TOMOGRAPHY; PARALYSIS; VOLUME; PEEP AB Objective: The approach to applying positive end-expiratory pressure in morbidly obese patients is not well defined. These patients frequently require prolonged mechanical ventilation, increasing the risk for failed liberation from ventilatory support. We hypothesized that lung recruitment maneuvers and titration of positive end-expiratory pressure were both necessary to improve lung volumes and the elastic properties of the lungs, leading to improved gas exchange. Design: Prospective, crossover, nonrandomized interventional study. Setting: Medical and surgical ICUs at Massachusetts General Hospital. Patients: Critically ill, mechanically ventilated morbidly obese (body mass index > 35 kg/m(2)) patients (n = 14). Interventions: This study evaluated two methods of titrating positive end-expiratory pressure; both trials were done utilizing positive end-expiratory pressure titration and recruitment maneuvers while measuring hemodynamics and respiratory mechanics. Measurements were obtained at the baseline positive end-expiratory pressure set by the clinicians, at zero positive end-expiratory pressure, at best positive end-expiratory pressure identified through esophageal pressure measurement before and after a recruitment maneuver, and at best positive end-expiratory pressure identified through a best decremental positive end-expiratory pressure trial. Measurements and Main Results: The average body mass index was 50.7 16.0 kg/m(2). The two methods of evaluating positive end-expiratory pressure identified similar optimal positive end-expiratory pressure levels (20.7 +/- 4.0 vs 21.3 +/- 3.8 cm H2O; p = 0.40). End-expiratory pressure titration increased end-expiratory lung volumes (11 +/- 7 mL/kg; p < 0.01) and oxygenation (86 +/- 50 torr; p < 0.01) and decreased lung elastance (5 +/- 5 cm H2O/L; p < 0.01). Recruitment maneuvers followed by titrated positive end-expiratory pressure were effective at increasing end-expiratory lung volumes while decreasing end-inspiratory transpulmonary pressure, suggesting an improved distribution of lung aeration and reduction of overdistension. The positive end-expiratory pressure levels set by the clinicians (11.6 +/- 2.9 cm H2O) were associated with lower lung volumes, worse elastic properties of the lung, and lower oxygenation. Conclusions: Commonly used positive end-expiratory pressure by clinicians is inadequate for optimal mechanical ventilation of morbidly obese patients. A recruitment maneuver followed by end-expiratory pressure titration was found to significantly improve lung volumes, respiratory system elastance, and oxygenation. C1 [Pirrone, Massimiliano; Imber, David A. E.; Corona, Javier; Mietto, Cristina; Kacmarek, Robert M.; Berra, Lorenzo] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Pirrone, Massimiliano; Mietto, Cristina] Univ Milan, Dipartimento Anestesiol Terapia Intens & Sci Derm, Milan, Italy. [Fisher, Daniel; Chipman, Daniel; Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Corona, Javier] Univ Complutense Madrid, Fac Med, Madrid, Spain. RP Berra, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM lberra@partners.org FU Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; Department of Anesthesia; Hollister; Covidien; Venner Medical; National Institutes of Health [T32]; Endoclear; LLC FX Supported, in part, by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital.; Dr. Pirrone's institution received grant support from the Department of Anesthesia to cover study-related expenses. Mr. Fisher received educational grant from Hollister. Dr. Kacmarek has received grants from Covidien and Venner Medical. He consulted for Covidien on mechanical ventilators. His institution received grant support (research grants from Venner Medical and Covidien). Dr. Berra received support for travel from E-motion (visit to the laboratory located in Tel Aviv, Israel). He and his institution received grant support from the National Institutes of Health (T32 training grant). His institution received grant support from Endoclear, LLC (Endoclear, LLC supported research-related expenses and provided devices for a study on endotracheal tube cleaning devices). The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 34 TC 6 Z9 7 U1 5 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2016 VL 44 IS 2 BP 300 EP 307 DI 10.1097/CCM.0000000000001387 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA DB4SO UT WOS:000368503700008 PM 26584196 ER PT J AU Taylor, BE McClave, SA Martindale, RG Warren, MM Johnson, DR Braunschweig, C McCarthy, MS Davanos, E Rice, TW Cresci, GA Gervasio, JM Sacks, GS Roberts, PR Compher, C AF Taylor, Beth E. McClave, Stephen A. Martindale, Robert G. Warren, Malissa M. Johnson, Debbie R. Braunschweig, Carol McCarthy, Mary S. Davanos, Evangelia Rice, Todd W. Cresci, Gail A. Gervasio, Jane M. Sacks, Gordon S. Roberts, Pamela R. Compher, Charlene CA Soc Critical Care Med Amer Soc Parenteral Enteral Nutr TI Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN) SO CRITICAL CARE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SEVERE ACUTE-PANCREATITIS; RESTING ENERGY-EXPENDITURE; MECHANICALLY VENTILATED PATIENTS; GAMMA-LINOLENIC ACID; INFLAMMATORY RESPONSE SYNDROME; INTENSIVE INSULIN THERAPY; PLACEBO-CONTROLLED TRIAL; MILD ACUTE-PANCREATITIS; TRAUMATIC BRAIN-INJURY C1 [Taylor, Beth E.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [McClave, Stephen A.] Univ Louisville, Dept Med, Louisville, KY 40292 USA. [Martindale, Robert G.] Oregon Hlth & Sci Univ, Div Gen Surg, Portland, OR 97201 USA. [Warren, Malissa M.] Portland VA Med Ctr, Portland, OR USA. [Johnson, Debbie R.] UW Hlth Univ, Wisconsin Hosp & Clin, Wound Skin Ost, Madison, WI USA. [Braunschweig, Carol] Univ Illinois, Dept Kinesiol & Nutr, Chicago, IL USA. [Braunschweig, Carol] Univ Illinois, Div Epidemiol & Biostat, Chicago, IL USA. [McCarthy, Mary S.] Madigan Healthcare Syst, Ctr Nursing Sci & Clin Inquiry, Tacoma, WA USA. [Davanos, Evangelia] Brooklyn Hosp Ctr, Nutr Support, Brooklyn, NY USA. [Rice, Todd W.] Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Med, Nashville, TN 37212 USA. [Cresci, Gail A.] Inst Digest Dis, Gastroenterol & Pathobiol, Cleveland, OH USA. [Gervasio, Jane M.] Butler Univ, Coll Pharm & Hlth Sci, Pharm Practice, Indianapolis, IN 46208 USA. [Sacks, Gordon S.] Auburn Univ, Dept Pharm Practice, Harrison Sch Pharm, Auburn, AL 36849 USA. [Roberts, Pamela R.] Univ Oklahoma, Hlth Sci Ctr, Dept Anesthesiol, Oklahoma City, OK 73190 USA. [Compher, Charlene] Univ Penn, Sch Nursing, Nutr Sci, Philadelphia, PA 19104 USA. RP Taylor, BE (reprint author), Barnes Jewish Hosp, St Louis, MO 63110 USA. EM bet1217@bjc.org FU Metagenics; Kabi USA, LLC; A.S.P.E.N. Rhoads Research Foundation - Board of Advisors; Fresenius Kabi USA, LLC; March of Dimes Foundation FX Dr. Taylor disclosed serving as an A.S.P.E.N. committee member and DNS past chair. Dr. McClave disclosed other relationships with Nestle (consulting), Abbott (Speaker), Metagenics (consulting), Covidien (consultant), and A.S.P.E.N. Dr. Martindale disclosed other relationships with Davol, LifeCell, and Metagenics (consultant) and received funding from Metagenics (research grant recipient). Dr. Warren disclosed serving as Co-chair for the Veterans Health Administration Dietary Supplement Committee and as a Chair for the Dietitians in Nutrition Support webinar planning committee. Dr. Braunschweig disclosed serving as the A.S.P.E.N. editor for clinical guidelines. Dr. McCarthy disclosed serving as an A.S.P.E.N. Committee Member for Research Committee and Abstract Review Committee, A.S.P.E.N. Nursing Section Member, and SCCM Nursing Section Member. Dr. Davanos disclosed other relationships with Baxter Healthcare (Medical Science Liaison and employee) and NY/LISPEN chapter (President Elect). Dr. Cresci disclosed other relatiosnhips with Metagenics, Advocare, and Covidien. She received funding from Metagenics (research grant, speaker) and served as a research committee member for A.S.P.E.N. and DNS (Chair - symposium planning committee). Dr. Rice disclosed other relationships with Avisa, LLC (Consultant) and GSK (DSMB). Dr. Roberts disclosed other relationships as ASA Committee Member (critical care) and as an A.S.P.E.N. Committee member (abstract reviews). Dr. Gervasio disclosed serving as an A.S.P.E.N. committee member. Dr. Sacks disclosed other relationships with Kabi USA, LLC (research grant recipient) and A.S.P.E.N. (President and member of Board of Directors, A.S.P.E.N. Rhoads Research Foundation - Board of Advisors); received funding (Research grant recipient, related to parenteral nutrition); and received funding from Fresenius Kabi USA, LLC (research grant recipient). Dr. Rice served as expert witness. Dr. Compher received funding from the March of Dimes Foundation (Research grant recipient) and disclosed other relationships with A.S.P.E.N. (Board of directors and President elect). Dr. Johnson disclosed that she does not have any potential conflicts of interest. NR 484 TC 21 Z9 27 U1 22 U2 36 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2016 VL 44 IS 2 BP 390 EP 438 DI 10.1097/CCM.0000000000001525 PG 49 WC Critical Care Medicine SC General & Internal Medicine GA DB4SO UT WOS:000368503700020 PM 26771786 ER PT J AU Leiter, LA Teoh, H Mosenzon, O Cahn, A Hirshberg, B Stahre, CAM Hoekstra, JBL Alvarsson, M Im, K Scirica, BM Bhatt, DL Raz, I AF Leiter, L. A. Teoh, H. Mosenzon, O. Cahn, A. Hirshberg, B. Stahre, C. A. M. Hoekstra, J. B. L. Alvarsson, M. Im, K. Scirica, B. M. Bhatt, D. L. Raz, I. TI Frequency of cancer events with saxagliptin in the SAVOR-TIMI 53 trial SO DIABETES OBESITY & METABOLISM LA English DT Article DE antihyperglycemic agents; cancer; saxagliptin ID RISK; METAANALYSIS; METFORMIN; PEOPLE AB The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 trial randomized trial of 16 492 patients (placebo, n = 8212; saxagliptin, n = 8280) treated and followed for a median of 2.1 years afforded an opportunity to explore whether there was any association with cancer reported as a serious adverse event. At least one cancer event was reported by 688 patients (4.1%): 362 (4.3%) and 326 (3.8%) in the placebo and saxagliptin arms, respectively (p = 0.13). There were 59 (0.6%) deaths adjudicated as malignancy deaths with placebo and 53 (0.6%) with saxagliptin. Stratification by gender, age, race and ethnicity, diabetes duration, baseline glycated haemoglobin and pharmacotherapy did not show any clinically meaningful differences between the two study arms. The overall number of cancer events and malignancy-associated mortality rates were generally balanced between the placebo and saxagliptin groups, suggesting a null relationship with saxagliptin use over the median follow-up of 2.1 years. Multivariable modelling showed that male gender, dyslipidaemia and current smoking were independent predictors of cancer. These randomized data with adequate numbers of cancer cases are reassuring but limited, by the short follow-up in a trial not designed to test this hypothesis. C1 [Leiter, L. A.; Teoh, H.] Univ Toronto, Div Endocrinol & Metab, Li Ka Shing Knowledge Inst, St Michaels Hosp, Toronto, ON, Canada. [Teoh, H.] Li Ka Shing Knowledge Inst, Div Cardiac Surg, Toronto, ON, Canada. [Teoh, H.] St Michaels Hosp, Keenan Res Ctr Biomed Sci, 30 Bond St, Toronto, ON M5B 1W8, Canada. [Mosenzon, O.; Cahn, A.; Raz, I.] Hadassah Hebrew Univ, Med Ctr, Diabetes Unit, Div Internal Med, Jerusalem, Israel. [Hirshberg, B.] AstraZeneca, Wilmington, DE USA. [Stahre, C. A. M.] AstraZeneca, Molndal, Sweden. [Hoekstra, J. B. L.] Univ Amsterdam, Internal Med, Amsterdam, Netherlands. [Alvarsson, M.] Karolinska Inst Solna, Mol Med & Surg, Endocrinol Metab & Diabet, Stockholm, Sweden. [Im, K.; Scirica, B. M.; Bhatt, D. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. RP Leiter, LA (reprint author), St Michaels Hosp Med Ctr, 61 Queen St East,6121Q, Toronto, ON M5C 2T2, Canada. EM leiterl@smh.ca FU AstraZeneca; Bristol-Myers Squibb FX The Executive Committee comprises Eugene Braunwald (Study Chair), Deepak L. Bhatt (Co-Principal Investigator), Itamar Raz (Co-Principal Investigator), Jaime A. Davidson, Robert Frederich (non-voting), Boaz Hirshberg (non-voting), Ph. Gabriel Steg. The SAVOR-TIMI 53 RCT was sponsored by AstraZeneca and Bristol-Myers Squibb and designed by the TIMI Study Group and Hadassah Medical Organization in conjunction with the sponsors, who provided monitoring support and provided the saxagliptin used. The authors gratefully acknowledge the efforts of the SAVOR-TIMI 53 patients, investigators, research coordinators and committee members. A complete list of the participating investigators and the Consolidated Standards of Reporting Trials (CONSORT) statement have been published [5]. NR 16 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD FEB PY 2016 VL 18 IS 2 BP 186 EP 190 DI 10.1111/dom.12582 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB6LK UT WOS:000368626300009 PM 26443993 ER PT J AU Laffel, L AF Laffel, Lori TI Improved Accuracy of Continuous Glucose Monitoring Systems in Pediatric Patients with Diabetes Mellitus: Results from Two Studies SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID EXCHANGE CLINIC REGISTRY; AUGMENTED PUMP THERAPY; CHILDREN AGED 4; GLYCEMIC CONTROL; BLOOD-GLUCOSE; FOLLOW-UP; STAR 3; TYPE-1; TRIAL; YOUTH AB Objective: This study was designed to evaluate accuracy, performance, and safety of the Dexcom (San Diego, CA) G4((R)) Platinum continuous glucose monitoring (CGM) system (G4P) compared with the Dexcom G4 Platinum with Software 505 algorithm (SW505) when used as adjunctive management to blood glucose (BG) monitoring over a 7-day period in youth, 2-17 years of age, with diabetes. Research Design and Methods: Youth wore either one or two sensors placed on the abdomen or upper buttocks for 7 days, calibrating the device twice daily with a uniform BG meter. Participants had one in-clinic session on Day 1, 4, or 7, during which fingerstick BG measurements (self-monitoring of blood glucose [SMBG]) were obtained every 305min for comparison with CGM, and in youth 6-17 years of age, reference YSI glucose measurements were obtained from arterialized venous blood collected every 155min for comparison with CGM. The sensor was removed by the participant/family after 7 days. Results: In comparison of 2,922 temporally paired points of CGM with the reference YSI measurement for G4P and 2,262 paired points for SW505, the mean absolute relative difference (MARD) was 17% for G4P versus 10% for SW505 (P<0.0001). In comparison of 16,318 temporally paired points of CGM with SMBG for G4P and 4,264 paired points for SW505, MARD was 15% for G4P versus 13% for SW505 (P<0.0001). Similarly, error grid analyses indicated superior performance with SW505 compared with G4P in comparison of CGM with YSI and CGM with SMBG results, with greater percentages of SW505 results falling within error grid Zone A or the combined Zones A plus B. There were no serious adverse events or device-related serious adverse events for either the G4P or the SW505, and there was no sensor breakoff. Conclusions: The updated algorithm offers substantial improvements in accuracy and performance in pediatric patients with diabetes. Use of CGM with improved performance has potential to increase glucose time in range and improve glycemic outcomes for youth. C1 [Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02115 USA. [Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02115 USA. RP Laffel, L (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect, One Joslin Pl, Boston, MA 02215 USA. EM Lori.Laffel@Joslin.Harvard.Edu FU Dexcom FX I would like to thank the participating sites, study staff, and the patients, acknowledging the site physicians and the bio-statistician from Dexcom: Andrew Ahmann, MD, Portland, OR; Timothy Bailey, MD, Clinical Research, Advanced Metabolic Care and Research Institute, Escondido, CA; Bruce Buckingham, MD, Stanford University School of Medicine, Palo Alto, CA; Peter Chase, MD, Pediatrics, Barbara Davis Center for Diabetes, Denver, CO; Mark Daniels, MD, Children's Hospital of Orange County, Orange, CA; David Liljenquist, MD, Diabetes and Osteoporosis Center, Rocky Mountain, Idaho Falls, ID; Eva Tsalikian, MD, UIHC Department of Pediatrics, University of Iowa, Iowa City, IA; and Katherine Nakamura, PhD, Dexcom, San Diego, CA. The clinical studies were funded by Dexcom. NR 39 TC 3 Z9 3 U1 3 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD FEB 1 PY 2016 VL 18 SU 2 BP 23 EP 33 DI 10.1089/dia.2015.0380 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB6DF UT WOS:000368602900002 PM 26784126 ER PT J AU Bailey, WM Mazur, A McCotter, C Woodard, PK Rosenthal, L Johnson, W Mela, T AF Bailey, William M. Mazur, Alexander McCotter, Craig Woodard, Pamela K. Rosenthal, Lawrence Johnson, Whitney Mela, Theofanie CA ProMRI Study Investigators TI Clinical safety of the ProMRI pacemaker system in patients subjected to thoracic spine and cardiac 1.5-T magnetic resonance imaging scanning conditions SO HEART RHYTHM LA English DT Article DE Bradycardia pacing; Clinical trial; ENTOVIS; Magnetic resonance imaging; Pacemaker; Safety; ProMRI ID IMPLANTABLE-CARDIOVERTER-DEFIBRILLATORS; DEVICES; PERFORMANCE; IMPACT; HEART; TESLA; LEAD AB BACKGROD Permanent cardiac pacemakers have historically been considered a contraindication to magnetic resonance imaging (MRI). OBJECTIVE The purpose of the ProMRI Phase B Study, a multicenter, prospective, single-arm, nonrandomized study, was to evaluate the clinical safety of the Biotronik ProMRI pacemaker system in patients undergoing thoracic spine and cardiac MRI. METHODS The ProMRI Phase B study enrolled 245 patients with stable baseline pacing indices implanted with an Entovis pacemaker (DR-T or SR-T) and Setrox 53-cm and/or 60-cm lead(s). Device interrogation was performed at enrollment, pre- and post-MRI scan, and 1 and 3 months post-MRI. End-points were (1) freedom from MRI- and pacing system-related serious adverse device effects through 1 month post-MRI; (2) freedom from atrial and ventricular MRI-induced pacing threshold increase (>0.5 V); and (3) freedom from P-and R-wave amplitude attenuation (<50%), or P wave <1.5 mV, or R wave <5.0 mV at 1 month post-MRI. RESULTS In total, 216 patients completed the MRI and 1-month post-MRI follow-up. One adverse event possibly related to the implanted system and the MRI procedure occurred, resulting in a serious adverse device effect-free rate of 99.6% (220/221; P < .0001. Freedom from atrial and ventricular pacing threshold increase was 1000/0 (194/194, P < .001) and 1000/0 (206/206, P < .001) respectively. Freedom from P-and R-wave amplitude attenuation was 98.2% (167/170, P < .001) and 1000/0 (188/188, P < .001) respectively. CONCLUSION The results of the ProMRI Phase B study demonstrate the clinical safety and efficacy of the ProMRI pacemaker system in patients subjected to thoracic spine and cardiac MRI conditions. C1 [Bailey, William M.] Louisiana Heart Rhythm Specialists, Lafayette, LA 70503 USA. [Bailey, William M.] Lafayette Gen Med Ctr, Lafayette, LA USA. [Mazur, Alexander] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [McCotter, Craig] Upstate Cardiol, Greenville, SC USA. [Woodard, Pamela K.] Washington Univ, Sch Med, St Louis, MO USA. [Rosenthal, Lawrence] Univ Massachusetts, Sch Med, Worcester, MA USA. [Johnson, Whitney] Biotronik Inc, Lake Oswego, OR USA. [Mela, Theofanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bailey, WM (reprint author), Louisiana Heart Rhythm Specialists, 913 South Coll Rd,Suite 103, Lafayette, LA 70503 USA. EM wbailey@heartrhythmmd.com OI McCotter, Craig/0000-0002-4366-2181 FU Biotronik; Biotronik Inc (Berlin); Biotronik Inc (Germany); Biotronik Inc (Lake Oswego OR) FX Dr. Bailey is a trial investigator; has received research support and speaking honoraria from Biotronik; and has served as a consultant for Biotronik. Dr. Mazur is a trial investigator and has received research support from Biotronik. Dr. McCotter is a trial investigator and has received research support from Biotronik. Dr. Woodard participated as a consultant to Biotronik for this trial. Ms. Johnson is an employee of Biotronik. Dr. Rosenthal is a trial investigator and has received research support from Biotronik. Dr. Mela is a trial investigator and has received research support from Biotronik. Biotronik Inc (Berlin, Germany; and Lake Oswego OR) provided funding for the trial and is the manufacturer of the pacemaker systems used in the trial. ClinicalTrials.gov Identifier: NCT02009696. NR 25 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD FEB PY 2016 VL 13 IS 2 BP 464 EP 471 DI 10.1016/j.hrthm.2015.09.021 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB2PM UT WOS:000368351500022 PM 26409098 ER PT J AU Wilkoff, BL Fauchier, L Stiles, MK Morillo, CA Al-Khatib, SM Almendral, J Aguinaga, L Berger, RD Cuesta, A Daubert, JP Dubner, S Ellenbogen, KA Estes, NAM Fenelon, G Garcia, FC Gasparini, M Haines, DE Healey, JS Hurtwitz, JL Keegan, R Kolb, C Kuck, KH Marinskis, G Martinelli, M McGuire, M Molina, LG Okumura, K Proclemer, A Russo, AM Singh, JP Swerdlow, CD Teo, WS Uribe, W Viskin, S Wang, CC Zhang, S AF Wilkoff, Bruce L. Fauchier, Laurent Stiles, Martin K. Morillo, Carlos A. Al-Khatib, Sana M. Almendral, Jesus Aguinaga, Luis Berger, Ronald D. Cuesta, Alejandro Daubert, James P. Dubner, Sergio Ellenbogen, Kenneth A. Estes, N. A. Mark, III Fenelon, Guilherme Garcia, Fermin C. Gasparini, Maurizio Haines, David E. Healey, Jeff S. Hurtwitz, Jodie L. Keegan, Roberto Kolb, Christof Kuck, Karl-Heinz Marinskis, Germanas Martinelli, Martino McGuire, Mark Molina, Luis G. Okumura, Ken Proclemer, Alessandro Russo, Andrea M. Singh, Jagmeet P. Swerdlow, Charles D. Teo, Wee Siong Uribe, William Viskin, Sami Wang, Chun-Chieh Zhang, Shu TI 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing SO HEART RHYTHM LA English DT Article DE Implantable cardioverter-defibrillator; Bradycardia mode and rate; Tachycardia detection; Tachycardia therapy; Defibrillation testing; Programming ID CARDIAC-RESYNCHRONIZATION THERAPY; QUALITY-OF-LIFE; FAST VENTRICULAR-TACHYCARDIA; SICK-SINUS SYNDROME; CLINICAL-PRACTICE GUIDELINES; DUAL-CHAMBER DEFIBRILLATORS; REDUCE INAPPROPRIATE SHOCKS; PRIMARY PREVENTION PATIENTS; RATE-RESPONSIVE PACEMAKERS; LONG-DETECTION INTERVAL C1 [Wilkoff, Bruce L.] Cleveland Clin, Cleveland, OH 44106 USA. [Fauchier, Laurent] CHU Trousseau, Tours, France. [Stiles, Martin K.] Waikato Hosp, Hamilton, New Zealand. [Morillo, Carlos A.] McMaster Univ, Dept Med, Div Cardiol, Populat Hlth Res Inst, Hamilton, ON, Canada. [Al-Khatib, Sana M.; Daubert, James P.] Duke Univ, Med Ctr, Durham, NC USA. [Almendral, Jesus] Univ CEU San Pablo, Grp HM Hosp, Madrid, Spain. [Aguinaga, Luis] Ctr Privado Cardiol, San Miguel De Tucuman, Argentina. [Berger, Ronald D.] Johns Hopkins Univ, Baltimore, MD USA. [Cuesta, Alejandro] Inst Cardiol Infantil, Serv Arritmias, Montevideo, Uruguay. [Dubner, Sergio] Clin & Maternidad Suizo Argentina & De Los Arcos, Buenos Aires, DF, Argentina. [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. [Estes, N. A. Mark, III] Tufts Univ New England Med Ctr, Boston, MA 02111 USA. [Fenelon, Guilherme] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Garcia, Fermin C.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Gasparini, Maurizio] Humanitas Res Hosp, Milan, Italy. [Haines, David E.] William Beaumont Hosp, Div Cardiol, Royal Oak, MI 48072 USA. [Hurtwitz, Jodie L.] North Texas Heart Ctr, Dallas, TX USA. [Keegan, Roberto] Hosp Privado Sur, Bahia Blanca, Buenos Aires, Argentina. [Kolb, Christof] Deutsch Herzzentrum Munich, Munich, Germany. [Kuck, Karl-Heinz] Allgemeines Krankenhaus St Georg, Hamburg, Germany. [Marinskis, Germanas] Vilnius State Univ, Clin Cardiac & Vasc Dis, Vilnius, Lithuania. [Martinelli, Martino] Univ Sao Paulo, Inst Coracao, Sao Paulo, Brazil. [McGuire, Mark] Royal Prince Alfred Hosp, Sydney, NSW, Australia. [Molina, Luis G.] Mexicos Natl Univ, Mexicos Gen Hosp, Mexico City, DF, Mexico. [Okumura, Ken] Hirosaki Univ, Grad Sch Med, Hirosaki, Aomori, Japan. [Proclemer, Alessandro] Azienda Osped Univ S Maria della Misericordia Udi, Udine, Italy. [Russo, Andrea M.] Cooper Univ Hosp, Camden, NJ USA. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Swerdlow, Charles D.] Cedars Sinai Med Ctr, Beverly Hills, CA USA. [Teo, Wee Siong] Natl Heart Ctr Singapore, Singapore, Singapore. [Uribe, William] CES Cardiol, Medellin, Colombia. [Uribe, William] Ctr Especializados San Vicente Fdn, Medellin, Colombia. [Uribe, William] CES Cardiol, Rionegro, Colombia. [Uribe, William] Ctr Especializados San Vicente Fdn, Rionegro, Colombia. [Viskin, Sami] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Viskin, Sami] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Wang, Chun-Chieh] Chang Gung Mem Hosp, Taipei 10591, Taiwan. [Zhang, Shu] Natl Ctr Cardiovasc Dis, Beijing, Peoples R China. [Zhang, Shu] Peking Union Med Coll, Beijing Fu Wai Hosp, Beijing 100021, Peoples R China. [Zhang, Shu] China Acad Med Sci, Beijing, Peoples R China. RP Wilkoff, BL (reprint author), Cleveland Clin, Cleveland, OH 44106 USA. NR 220 TC 18 Z9 18 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD FEB PY 2016 VL 13 IS 2 BP E50 EP E86 DI 10.1016/j.hrthm.2015.11.018 PG 37 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB2PM UT WOS:000368351500002 PM 26607062 ER PT J AU Post, RM Altshuler, LL Kupka, R McElroy, SL Frye, MA Rowe, M Grunze, H Suppes, T Keck, PE Leverich, GS Nolen, WA AF Post, Robert M. Altshuler, Lori L. Kupka, Ralph McElroy, Susan L. Frye, Mark A. Rowe, Michael Grunze, Heinz Suppes, Trisha Keck, Paul E. Leverich, Gabriele S. Nolen, Willem A. TI More illness in offspring of bipolar patients from the US compared to Europe SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE Depression; Substance abuse; Anxiety disorder; Family history; Suicide attempt ID UNITED-STATES; EARLY-ONSET; N-ACETYLCYSTEINE; EARLY AGE; DISORDER; RISK; TRIAL; ADOLESCENTS; GENERATIONS; STRATEGIES AB Background: Evidence suggests that patients with bipolar disorder from the United States have an earlier age of onset and a more difficult course of illness than those from Germany and the Netherlands. These characteristics were related to a greater family burden of psychiatric illness and the experience of more psychosocial adversity in childhood. We hypothesized that this greater illness burden would extend to the offspring of the US patients. Methods: 968 outpatients (average age 41) with bipolar illness gave informed consent for participation in a treatment outcome network and filled out a detailed questionnaire about their illness and family history of illness, including whether their offspring had a diagnosis of depression, bipolar disorder, alcohol or substance abuse, suicide attempt or "other" illness. Of those with children, 356 were from the US and 132 were from Europe. Results: Compared to the Europeans, offspring of patients from the US had significantly (p < 0.001) more depression, bipolar disorder, drug abuse, and "other" illnesses. The number of illnesses in the offspring was related to the bipolar parent being from the US, having had childhood adversity, more than 20 prior episodes, and more parental psychiatric illness. Conclusions: While the findings are limited by their basis on self report, the distribution of the percentages in the US offspring are similar to those of Axelson et al. (2015) who used direct interviews. The higher burden of illness in the offspring and their in direct progenitors from the US compared to Europe warrant new attempts at better treatment and prevention. (c) 2016 The Authors. Published by Elsevier B.V. C1 [Post, Robert M.; Rowe, Michael; Leverich, Gabriele S.] Bipolar Collaborat Network, Bethesda, MD 20814 USA. [Post, Robert M.] George Washington Univ, Dept Psychiat & Behav Sci, Washington, DC USA. [Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, West Los Angeles Healthcare Ctr, Dept Psychiat, Los Angeles, CA USA. [Kupka, Ralph; Keck, Paul E.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [McElroy, Susan L.; Keck, Paul E.] Lindner Ctr HOPE, Mason, OH USA. [McElroy, Susan L.] Univ Cincinnati, Coll Med, Biol Psychiat Program, Cincinnati, OH USA. [Frye, Mark A.] Mayo Clin, Dept Psychiat, Rochester, MI USA. [Grunze, Heinz] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Suppes, Trisha] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Suppes, Trisha] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Altshuler, Lori L.] UCLA Mood Disorders Res Program, Mood Disorders Res, Los Angeles, CA USA. RP Post, RM (reprint author), Bipolar Collaborat Network, Bethesda, MD 20814 USA. EM Robert.post@speakeasy.net OI Grunze, Heinz/0000-0003-4712-8979 NR 44 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB PY 2016 VL 191 BP 180 EP 186 DI 10.1016/j.jad.2015.11.038 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DB1FL UT WOS:000368253400025 PM 26655863 ER PT J AU Kim, K Hong, JP Cho, MJ Fava, M Mischoulon, D Lee, DW Heo, JY Jeon, HJ AF Kim, Kiwon Hong, Jin Pyo Cho, Maeng Je Fava, Maurizio Mischoulon, David Lee, Dong-Woo Heo, Jung-Yoon Jeon, Hong Jin TI Loss of sexual interest and premenstrual mood change in women with postpartum versus non-postpartum depression: A nationwide community sample of Korean adults SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Loss of sexual interest; Loss of confidence; Loss of pleasure; Premenstrual mood change; Postpartum depression ID ASTERISK-D-CHILD; PERINATAL DEPRESSION; POSTNATAL DEPRESSION; MENSTRUAL-CYCLE; SELF-HARM; SUICIDAL IDEATION; MENTAL-DISORDERS; PREGNANCY; PREVALENCE; PERIOD AB Background: Postpartum depression (PPD) is a type of clinical depression that can affect women after childbirth. Few previous studies have explored the association of depressive and physical symptoms among women with PPD in a nationwide community study. Method: A total of 18,807 adults, randomly selected, completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI) (response rate 80.2%). PPD was defined as a major depressive episode that began within 4 weeks after delivery. Results: Of 679 female subjects with major depressive disorder (MDD), 14.0% (n=95) experienced PPD. Subjects with PPD were significantly more likely to have higher income, education, and reside in an urban area, compared to those with non-PPD. No significant differences were found in number of children. Multiple logistic regression revealed that the loss of sexual interest was the only symptom among 23 depressive symptoms that was significantly associated with depressive episodes among individuals with PPD (AOR= 1.91, 95% Cl 1.01-3.60) when compared with non-PPD. Loss of sexual interest was also significantly associated with the subjects with lifetime PPD regardless of depressive episode (AOR= 1.93, 95% Cl 1.12-3.31). Conversely, loss of confidence and loss of pleasure were less frequent in subjects with PPD. Premenstrual mood change (x(2)=5.57, p=0.0036) and comorbid alcohol use disorder (X-2 =5.11, p=0.031) showed a valid association with PPD. Conclusions: Loss of sexual interest and premenstrual mood change were associated with women with PPD, whereas those with non-PPD were not, thereby suggesting the possible link between sexual hormones and PPD. (c) 2015 Elsevier BY. All rights reserved. C1 [Kim, Kiwon; Hong, Jin Pyo; Heo, Jung-Yoon; Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul 135710, South Korea. [Cho, Maeng Je] Seoul Natl Univ, Coll Med, Dept Psychiat, Seoul, South Korea. [Fava, Maurizio; Mischoulon, David; Jeon, Hong Jin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Lee, Dong-Woo] Inje Univ, Coll Med, Sanggye Paik Hosp, Dept Psychiat, Seoul, South Korea. [Jeon, Hong Jin] Sungkyunkwan Univ, SAIHST, Dept Hlth Sci & Technol, Seoul 135710, South Korea. [Jeon, Hong Jin] Sungkyunkwan Univ, SAIHST, Dept Med Device Management & Res, Seoul 135710, South Korea. [Jeon, Hong Jin] Sungkyunkwan Univ, SAIHST, Dept Clin Res Design & Evaluat, Seoul 135710, South Korea. RP Jeon, HJ (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, 81 Irwon Ro, Seoul 135710, South Korea. EM jeonhj@skku.edu FU Korean Ministry of Health Welfare; Basic Science Research Program through National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2011-0013064]; Samsung Medical Center Clinical Research Development Program (CRDP) [SMO1131461] FX The authors wish to express their gratitude to 12 local investigators and 160 interviewers. This study was supported by the Korean Ministry of Health & Welfare. This research was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2011-0013064) (PI: Hong Jin Jeon, MD, Ph.D.). This study was also supported by the Samsung Medical Center Clinical Research Development Program (CRDP) Grant SMO1131461 (PI: Hong Jin Jeon, MD, Ph.D.). The authors thank the Samsung Statistical Support Team, Chief Dr. Seon-Woo Kim and Dr. Keumhee Cho for statistical support. These funding sources were not involved in the creation of the study protocol, data analysis, or in writing the manuscript. NR 77 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB PY 2016 VL 191 BP 222 EP 229 DI 10.1016/j.jad.2015.11.050 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DB1FL UT WOS:000368253400029 PM 26682491 ER PT J AU Vanmarcke, S Van der Hallen, R Evers, K Noens, I Steyaert, J Wagemans, J AF Vanmarcke, Steven Van der Hallen, Ruth Evers, Kris Noens, Ilse Steyaert, Jean Wagemans, Johan TI Ultra-Rapid Categorization of Meaningful Real-Life Scenes in Adults With and Without ASD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Vision research; Ultra-rapid categorization; Theory of mind; Reverse hierarchy theory ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; VISUAL CATEGORIZATION; SOCIAL-PERCEPTION; IMPLICIT THEORY; WEAK COHERENCE; MIND; OBJECTS; CHILDREN; TASK AB In comparison to typically developing (TD) individuals, people with autism spectrum disorder (ASD) appear to be worse in the fast extraction of the global meaning of a situation or picture. Ultra-rapid categorization [paradigm developed by Thorpe et al. (Nature 381:520-522, 1996)] involves such global information processing. We therefore tested a group of adults with and without ASD, without intellectual disability, on a set of ultra-rapid categorization tasks. Individuals with ASD performed equally well as TD individuals except when the task required the categorization of social interactions. These results argue against a general deficit in ultra-rapid gist perception in people with ASD, while suggesting a more specific problem with the fast processing of information about social relations. C1 [Vanmarcke, Steven; Van der Hallen, Ruth; Evers, Kris; Wagemans, Johan] Univ Leuven KU Leuven, Dept Brain & Cognit, Expt Psychol Lab, B-3000 Louvain, Belgium. [Van der Hallen, Ruth; Evers, Kris; Steyaert, Jean] UPC KU Leuven, Dept Child Psychiat, Louvain, Belgium. [Vanmarcke, Steven; Van der Hallen, Ruth; Evers, Kris; Noens, Ilse; Steyaert, Jean; Wagemans, Johan] Katholieke Univ Leuven, Leuven Autism Res LAuRes, Louvain, Belgium. [Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, Louvain, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Vanmarcke, S (reprint author), Univ Leuven KU Leuven, Dept Brain & Cognit, Expt Psychol Lab, B-3000 Louvain, Belgium.; Vanmarcke, S (reprint author), Katholieke Univ Leuven, Leuven Autism Res LAuRes, Louvain, Belgium. EM steven.vanmarcke@ppw.kuleuven.be FU Flemish Government [METH/08/02]; Research Foundation-Flanders (FWO) FX This work was supported by the Research Foundation-Flanders (FWO) to Steven Vanmarcke and long-term structural funding by the Flemish Government (METH/08/02) to Johan Wagemans. The authors would like to thank Nadege Mace, Michelle Fabre-Thorpe and Simon Thorpe for providing us with their stimulus material used in previous papers (e.g., Mace et al. 2009). A substantial subset of these images was used in the animal/vehicle task. We also thank Maarten Demeyer and Bart Machilsen for their help with programming in PsychoPy, Thomas Schouteden for his assistance with data collection and all participants for their time and contribution to this research. NR 95 TC 3 Z9 3 U1 6 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD FEB PY 2016 VL 46 IS 2 SI SI BP 450 EP 466 DI 10.1007/s10803-015-2583-6 PG 17 WC Psychology, Developmental SC Psychology GA DB7HP UT WOS:000368685700009 PM 26349920 ER PT J AU Halbert, CH Melvin, C Briggs, V Delmoor, E Rice, LJ Lynch, C Jefferson, M Johnson, JC AF Halbert, Chanita Hughes Melvin, Cathy Briggs, Vanessa Delmoor, Ernestine Rice, LaShanta J. Lynch, Cheryl Jefferson, Melanie Johnson, Jerry C. TI Neighborhood Satisfaction and Colorectal Cancer Screening in a Community Sample of African Americans SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Neighborhood satisfaction; Social determinants; Colorectal cancer screening; African Americans ID HEALTH; COLONOSCOPY; VALIDATION; VEGETABLES; KNOWLEDGE; COLLEGE; ACCESS; FRUITS; WOMEN AB Social determinants are important to cancer screening among African Americans. To evaluate the association between social determinants (e.g., psychological characteristics, perceived social environment, cultural beliefs such as present temporal orientation) and colorectal cancer (CRC) screening among African Americans. African American adults (n = 262) ages 50-75 completed a telephone interview. Multivariate logistic regression analysis was used to identify factors having significant independent associations with CRC screening. Only 57 % of respondents reported having CRC screening. The likelihood of screening increased with greater neighborhood satisfaction (OR = 1.38, 95 % CI = 1.01, 1.90, p = 0.04), older age (OR = 1.75, 95 % CI = 1.24, 2.48, p = 0.002), greater self-efficacy (OR = 2.73, 95 % CI = 1.40, 5.35, p = 0.003), and health care provider communication (OR = 10.78, 95 % CI = 4.85, 29.94, p = 0.0001). Community resources are important precursors to CRC screening and outcomes among African Americans. In addition to addressing psychological factors and patient-provider communication, efforts to ensure the availability of quality health care facilities that provide CRC screening in the neighborhoods where African Americans live are needed. C1 [Halbert, Chanita Hughes; Rice, LaShanta J.; Jefferson, Melanie] Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Populat Hlth & Outcomes, 68 President St,Suite BE103, Charleston, SC 29425 USA. [Halbert, Chanita Hughes] Ralph H Johnson Vet Adm Med Ctr, 68 President St,Suite BE103, Charleston, SC 29425 USA. [Melvin, Cathy] Med Univ S Carolina, Hollings Canc Ctr, 68 President St,Suite BE103, Charleston, SC 29425 USA. [Melvin, Cathy] Med Univ S Carolina, Dept Publ Hlth Sci, 68 President St,Suite BE103, Charleston, SC 29425 USA. [Briggs, Vanessa] Public Hlth Management Corp, Hlth Promot Serv, 260 South Broad St, Philadelphia, PA 19102 USA. [Delmoor, Ernestine] Natl Black Leadership Initiat Canc, Philadelphia Chapter, 1415 N Broad St,Suite 221B, Philadelphia, PA 19122 USA. [Lynch, Cheryl] Med Univ S Carolina, Div Gen Internal Med, Dept Med, 135 Rutledge Ave, Charleston, SC 29425 USA. [Lynch, Cheryl] Ralph H Johnson Vet Adm Med Ctr, 135 Rutledge Ave, Charleston, SC 29425 USA. [Johnson, Jerry C.] Univ Penn, Dept Med, Div Geriatr, 3615 Chestnut St, Philadelphia, PA 19104 USA. RP Halbert, CH (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Populat Hlth & Outcomes, 68 President St,Suite BE103, Charleston, SC 29425 USA.; Halbert, CH (reprint author), Ralph H Johnson Vet Adm Med Ctr, 68 President St,Suite BE103, Charleston, SC 29425 USA. EM hughesha@musc.edu FU National Cancer Institute [R01CA100254]; National Institute on Minority Health and Health Disparities Grant [R24MD001594] FX This research was supported by National Cancer Institute Grant No. R01CA100254 and National Institute on Minority Health and Health Disparities Grant No. R24MD001594. We would like to Benita Weathers, MPH for project management, Aliya Collier, BA for data management, Stacey Brown, MSW for data collection and administration, and Brenda Bryant, BA for community outreach and relations. We are very appreciative to all of the women and men who participated in this research. NR 35 TC 1 Z9 1 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 EI 1573-3610 J9 J COMMUN HEALTH JI J. Community Health PD FEB PY 2016 VL 41 IS 1 BP 38 EP 45 DI 10.1007/s10900-015-0062-9 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DB6PY UT WOS:000368638400006 PM 26184107 ER PT J AU Jha, A Lin, L Savoia, E AF Jha, Ayan Lin, Leesa Savoia, Elena TI The Use of Social Media by State Health Departments in the US: Analyzing Health Communication Through Facebook SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Social media; Health communication; State Health Department; Facebook; CDC ID INFORMATION; ADOPTION AB The use of social media as a powerful health communication tool is an area of current research interest. Our objective was to describe use of Facebook by State Health Departments (SHDs) in US, and their relationship with CDC's Behavioral Risk Factor Surveillance System (BRFSS) data. Facebook pages of 34 SHDs were studied over a 200 day period, coding 2597 posts into 19 broad health communication categories. Mean number of Facebook posts per SHD was 76.4 (range 34-133); most frequent topic areas included healthy living (12 %), communicable diseases (9 %), vaccines and immunization (7 %), emergency preparedness and response (7 %), infant and child health (5 %), smoking and tobacco use (5 %), and miscellaneous (32 %). Through web-based interactive graphics (Google motion charts), we contrasted Facebook posts with CDC's BRFSS data on adult nutrition and physical activity, vaccination, smoking, adolescent health and road traffic accidents. Our research finds an apparent disconnect between content provided on Facebook by SHDs and the health conditions that affect their populations. Acknowledging the severe limitations in funding and human resources faced by the SHDs, our research attempts to present the factual situation in embracing a vastly popular social media platform for health communication. We believe there is a need for research exploring methods to balance the demands and resources. C1 [Jha, Ayan] CAMC, CAMC Hlth Educ & Res Inst, 3211 Maccorkle Ave SE, Charleston, WV 25304 USA. [Lin, Leesa] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Lin, Leesa] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Lin, Leesa; Savoia, Elena] 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. RP Jha, A (reprint author), CAMC, CAMC Hlth Educ & Res Inst, 3211 Maccorkle Ave SE, Charleston, WV 25304 USA. EM ayanjha@mail.harvard.edu FU U.S. Centers for Disease Control and Prevention (CDC) [1U90TP000417-05, 5PO1TP000307-05] FX We acknowledge funding support from the U.S. Centers for Disease Control and Prevention (CDC) cooperative agreement numbers: 1U90TP000417-05 (Preparedness and Emergency Response Learning Center) and 5PO1TP000307-05 (Preparedness and Emergency Response Research Center) Supplement. The content of this publication as well as the views and discussions expressed in this paper are solely those of the authors and do not necessarily represent the views of any partner organizations, the CDC or the U.S. Department of Health and Human Services nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. NR 18 TC 2 Z9 2 U1 11 U2 30 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 EI 1573-3610 J9 J COMMUN HEALTH JI J. Community Health PD FEB PY 2016 VL 41 IS 1 BP 174 EP 179 DI 10.1007/s10900-015-0083-4 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DB6PY UT WOS:000368638400023 PM 26318742 ER PT J AU Muluke, M Gold, T Kiefhaber, K Al-Sahli, A Celenti, R Jiang, H Cremers, S Van Dyke, T Schulze-Spate, U AF Muluke, M. Gold, T. Kiefhaber, K. Al-Sahli, A. Celenti, R. Jiang, H. Cremers, S. Van Dyke, T. Schulze-Spaete, U. TI Diet-Induced Obesity and Its Differential Impact on Periodontal Bone Loss SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE palmitic acid; oleic acid; high-fat diet; bone metabolism; inflammation; osteoclast ID NECROSIS-FACTOR-ALPHA; PORPHYROMONAS-GINGIVALIS; PALMITIC ACID; MEDITERRANEAN DIET; FATTY-ACIDS; OLEIC-ACID; IN-VIVO; DISEASE; INFLAMMATION; TISSUE AB Obesity is associated with abnormal lipid metabolism and impaired bone homeostasis. The aim of our study was to investigate the impact of specific elevated fatty acid (FA) levels on alveolar bone loss in a Porphyromonas gingivalis-induced model of periodontal disease and to analyze underlying cellular mechanisms in bone-resorbing osteoclasts and bone-forming osteoblasts in mice. Four-week-old male C57BL/6 mice were randomly divided in groups and subjected to a palmitic acid (PA)- or oleic acid (OA)-enriched high-fat diet (HFD) (20% of calories from FA) or a normal caloric diet (C group) (10% of calories from FA) for 16 wk. Starting at week 10, mice were infected orally with P. gingivalis (W50) or placebo to induce alveolar bone loss. Animals were sacrificed, and percentage fat, serum inflammation (tumor necrosis factor [TNF]-alpha), and bone metabolism (osteocalcin [OC], carboxy-terminal collagen crosslinks [CTX], and N-terminal propeptides of type I procollagen [P1NP]) markers were measured. Osteoblasts and osteoclasts were cultured in the presence of elevated PA or OA levels and exposed to P. gingivalis. Animals on FA-enriched diets weighed significantly more compared with animals on a normal caloric diet (P < 0.05). Both obese groups had similar percentages of fat (P = nonsignificant); however, alveolar bone loss was significantly greater in animals that were on the PA-enriched HFD (P < 0.05). TNF-alpha levels were highest in the PA group (P < 0.001) and increased in all groups in response to P. gingivalis inoculation (P < 0.01), whereas bone remodeling markers OC, CTX, and P1NP were lowest in the PA group (P < 0.001) and highest in the C group. Bacterial challenge decreased bone metabolism markers in all groups (P < 0.01). Further, osteoclasts showed an augmented inflammatory response to P. gingivalis in the presence of hyperlipidemic PA levels as opposed to OA cultures, which responded similarly to controls. These findings indicate that the specific FA profile of diet rather than weight gain and obesity alone modulates bone metabolism and can therefore influence alveolar bone loss. C1 [Muluke, M.; Gold, T.; Kiefhaber, K.; Al-Sahli, A.; Celenti, R.; Schulze-Spaete, U.] Columbia Univ, Coll Dent Med, Div Periodont, 630 W 168th St,PH7C-200C, New York, NY 10032 USA. [Muluke, M.; Gold, T.; Kiefhaber, K.] Columbia Univ, Inst Human Nutr, 630 W 168th St,PH7C-200C, New York, NY 10032 USA. [Jiang, H.; Cremers, S.] Columbia Univ, Med Ctr, Irving Inst Clin & Translat Res, 630 W 168th St,PH7C-200C, New York, NY 10032 USA. [Van Dyke, T.] Forsyth Inst, Boston, MA USA. RP Schulze-Spate, U (reprint author), Columbia Univ, Coll Dent Med, Div Periodont, 630 W 168th St,PH7C-200C, New York, NY 10032 USA.; Schulze-Spate, U (reprint author), Columbia Univ, Coll Dent Med, 630 W 168th St,PH7C-200C, New York, NY 10032 USA. EM us2141@cumc.columbia.edu FU National Institute of Dental and Craniofacial Research, National Center for Advancing Translational Sciences [K08DE018968, UL1 TR000040] FX This study was supported by National Institute of Dental and Craniofacial Research K08DE018968, UL1 TR000040, National Center for Advancing Translational Sciences. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 40 TC 2 Z9 2 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2016 VL 95 IS 2 BP 223 EP 229 DI 10.1177/0022034515609882 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DB4TY UT WOS:000368507500013 PM 26450512 ER PT J AU AlJaroudi, WA Hage, FG AF AlJaroudi, Wael A. Hage, Fadi G. TI Review of cardiovascular literature SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material C1 [AlJaroudi, Wael A.] Clemenceau Med Ctr, Div Cardiovasc Med, Beirut, Lebanon. [Hage, Fadi G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Lyons Harrison Res Bldg 306,1720 2nd AVE S, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Lyons Harrison Res Bldg 306,1720 2nd AVE S, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD FEB PY 2016 VL 23 IS 1 BP 8 EP 10 DI 10.1007/s12350-015-0343-9 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DB6CQ UT WOS:000368601300004 PM 26626784 ER PT J AU Iskandrian, AE Roth, CP Hage, FG AF Iskandrian, Ami E. Roth, Christopher P. Hage, Fadi G. TI Serial imaging and outcome prediction SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material ID CORONARY-ARTERY-DISEASE; LEFT-VENTRICULAR PERFUSION; MYOCARDIAL-PERFUSION; QUANTITATIVE-ANALYSIS; ASYMPTOMATIC PATIENTS; TRIAL; ISCHEMIA; ADENOSINE; NUCLEAR; SPECT C1 [Iskandrian, Ami E.; Roth, Christopher P.; Hage, Fadi G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, 318 LHRB,1900 Univ BLVD, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Iskandrian, AE (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, 318 LHRB,1900 Univ BLVD, Birmingham, AL 35294 USA. EM aiskand@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 21 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD FEB PY 2016 VL 23 IS 1 BP 117 EP 121 DI 10.1007/s12350-015-0312-3 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DB6CQ UT WOS:000368601300019 PM 26514576 ER PT J AU AlJaroudi, WA Hage, FG AF AlJaroudi, Wael A. Hage, Fadi G. TI Review of cardiovascular imaging in the journal of nuclear cardiology in 2015. Part 1 of 2: Plaque imaging, positron emission tomography, computed tomography, and magnetic resonance SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Review DE Vulnerable atherosclerotic plaque; myocardial perfusion imaging: PET; fluorodeoxyglucose (FDG); computed tomography (CT); magnetic resonance imaging ID CORONARY-ARTERY-DISEASE; SCREENING ASYMPTOMATIC PATIENTS; MYOCARDIAL-ISCHEMIA; CARDIAC AMYLOIDOSIS; HIV-INFECTION; MR-IMPACT; PET; ATHEROSCLEROSIS; INFLAMMATION; TRIAL AB In 2015, many original articles pertaining to cardiovascular imaging with impressive quality were published in the Journal of Nuclear Cardiology. In a set of 2 articles, we provide an overview of these contributions to facilitate for the interested reader a quick review of the advancements that occurred in the field over this year. In this first article, we focus on arterial plaque imaging, cardiac positron emission tomography, computed tomography, and magnetic resonance imaging. C1 [AlJaroudi, Wael A.] Clemenceau Med Ctr, Cardiovasc Imaging, Div Cardiovasc Med, Beirut, Lebanon. [Hage, Fadi G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Lyons Harrison Res Bldg 314,1720 2nd AVE S, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Lyons Harrison Res Bldg 314,1720 2nd AVE S, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 43 TC 1 Z9 1 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD FEB PY 2016 VL 23 IS 1 BP 122 EP 130 DI 10.1007/s12350-015-0319-9 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DB6CQ UT WOS:000368601300020 PM 26542991 ER PT J AU Steverson, D Tian, L Fu, YC Zhang, W Ma, E Garvey, WT AF Steverson, Dennis, Jr. Tian, Ling Fu, Yuchang Zhang, Wei Ma, Elizabeth Garvey, William Timothy TI Tribbles Homolog 3 Promotes Foam Cell Formation Associated with Decreased Proinflammatory Cytokine Production in Macrophages: Evidence for Reciprocal Regulation of Cholesterol Uptake and Inflammation SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; MOUSE PERITONEAL-MACROPHAGES; CARDIOVASCULAR-DISEASE; NLRP3 INFLAMMASOMES; INSULIN-RESISTANCE; METABOLIC SYNDROME; DEFICIENT MICE; ATHEROSCLEROSIS; PLAQUES; TRB3 AB Background: Insulin resistance is central in the pathophysiology of cardiometabolic disease; however, common mechanisms that explain the parallel development of both type 2 diabetes and atherosclerosis have not been elucidated. We have previously shown that tribbles homolog 3 (TRB3) can exert a chronic pathophysiological role in promoting insulin resistance and also has an acute physiological role to alternatively regulate glucose uptake in fat and muscle during short-term fasting and nutrient excess. Since TRB3 is expressed in human atherosclerotic plaques, we explored its role in foam cell formation to assess its potential contribution to atherogenesis. Methods: We have used human THP-1 monocytes, which transition to lipid-laden macrophage foam cells when exposed to oxidized low-density lipoprotein (ox-LDL). Results: We first observed that TRB3 was upregulated by more than twofold (P<0.01) within 24hr of treatment with ox-LDL. To determine whether TRB3 actively participated in foam cell formation, we overexpressed TRB3 in THP-1 monocytes and found that this led to a 1.5-fold increase in cholesterol accumulation after 48hr (P<0.01), compared with controls. At the same time, TRB3 overexpression suppressed inflammation in macrophages as evidenced by reduced expression and secretion of tumor necrosis factor alpha (TNF-) and interleukin-1 beta (IL-1) (both P<0.01). Conclusions: (1) TRB3 is upregulated in macrophages upon treatment with ox-LDL; (2) TRB3 promotes lipid accumulation and suppresses cytokine expression; and (3) inflammation and foam cell formation can be reciprocally regulated, and TRB3 orients the macrophage to assume a more primary role for lipid accumulation while maintaining a secondary role as an inflammatory immune cell. C1 [Steverson, Dennis, Jr.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Steverson, Dennis, Jr.; Tian, Ling; Fu, Yuchang; Zhang, Wei; Ma, Elizabeth; Garvey, William Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, William Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Steverson, D (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, 1675 Univ Blvd, Birmingham, AL 35294 USA. EM dsteversonjr@gmail.com FU National Institutes of Health [DK-038765, DK-083562]; Merit Review program of the Department of Veterans Affairs FX This work was supported by grants from the National Institutes of Health (DK-038765, DK-083562) and by the Merit Review program of the Department of Veterans Affairs. The authors also acknowledge support from core facilities of the UAB Diabetes Research Center (P30 DK079626). NR 39 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 1540-4196 EI 1557-8518 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD FEB 1 PY 2016 VL 14 IS 1 BP 7 EP 15 DI 10.1089/met.2015.0037 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DB4XT UT WOS:000368517600003 PM 26584255 ER PT J AU Ensan, S Li, A Besla, R Degousee, N Cosme, J Roufaiel, M Shikatani, EA El-Maldizil, M Williams, JW Robins, L Li, C Lewis, B Yun, TJ Lees, JS Wieghofer, P Khattar, R Farrokhil, K Byrne, J Ouzounian, M Zavitz, CCJ Levy, GA Bauer, CMT Libby, P Husain, M Swirski, FK Cheong, C Prinz, M Hilgendorf, I Randolph, GJ Epelman, S Gramolini, AO Cybulksky, MI Rubin, BB Robbins, CS AF Ensan, Sherine Li, Angela Besla, Rickvinder Degousee, Norbert Cosme, Jake Roufaiel, Mark Shikatani, Eric A. El-Maldizil, Mahmoud Williams, Jesse W. Robins, Lauren Li, Cedric Lewis, Bonnie Yun, Tae Jin Lees, Jun Seong Wieghofer, Peter Khattar, Ramzi Farrokhil, Kaveh Byrne, John Ouzounian, Maral Zavitz, Caleb C. J. Levy, Gary A. Bauer, Carla M. T. Libby, Peter Husain, Mansoor Swirski, Filip K. Cheong, Cheolho Prinz, Marco Hilgendorf, Ingo Randolph, Gwendalyn J. Epelman, Slava Gramolini, Anthony O. Cybulksky, Myron I. Rubin, Barry B. Robbins, Clinton S. TI Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth SO NATURE IMMUNOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; DENDRITIC CELLS; YOLK-SAC; CHEMOKINE FRACTALKINE; COMMITTED PROGENITORS; CARDIAC MACROPHAGES; TISSUE MACROPHAGES; FETAL MONOCYTES; STEADY-STATE; ADULT LIFE AB Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1(+) precursors and postnatally from bone marrow derived monocytes that colonize the tissue immediately after birth. In adulthood, proliferation (rather than monocyte recruitment) sustains arterial macrophages in the steady state and after severe depletion following sepsis. After infection, arterial macrophages return rapidly to functional homeostasis. Finally, survival of resident arterial macrophages depends on a CX3CR1-CX3CL1 axis within the vascular niche. C1 [Ensan, Sherine; Li, Angela; El-Maldizil, Mahmoud; Farrokhil, Kaveh; Epelman, Slava; Robbins, Clinton S.] Univ Toronto, Dept Immunol, Toronto, ON, Canada. [Besla, Rickvinder; Shikatani, Eric A.; Husain, Mansoor; Cybulksky, Myron I.; Robbins, Clinton S.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Degousee, Norbert; Cosme, Jake; Roufaiel, Mark; Robins, Lauren; Li, Cedric; Lewis, Bonnie; Khattar, Ramzi; Ouzounian, Maral; Zavitz, Caleb C. J.; Levy, Gary A.; Husain, Mansoor; Epelman, Slava; Gramolini, Anthony O.; Cybulksky, Myron I.; Rubin, Barry B.; Robbins, Clinton S.] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada. [Williams, Jesse W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Yun, Tae Jin; Lees, Jun Seong] Inst Rech Clin Montreal, Lab Cellular Physiol & Immunol, Montreal, PQ H2W 1R7, Canada. [Yun, Tae Jin; Lees, Jun Seong] Univ Freiburg, Inst Neuropathol, Hugstetter Str 55, D-79106 Freiburg, Germany. [Wieghofer, Peter] Univ Freiburg, Fac Biol, Hugstetter Str 55, D-79106 Freiburg, Germany. [Bauer, Carla M. T.] Hoffmann La Roche Inc, pRED, Pharma Res & Early Dev, DTA Inflammat, 340 Kingsland St, Nutley, NJ 07110 USA. [Libby, Peter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Swirski, Filip K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Prinz, Marco] Univ Freiburg, Inst Neuropathol, Hugstetter Str 55, D-79106 Freiburg, Germany. [Prinz, Marco] Univ Freiburg, BIOSS Ctr Biol Signaling Studies, Hugstetter Str 55, D-79106 Freiburg, Germany. [Hilgendorf, Ingo] Univ Freiburg, Dept Cardiol & Angiol 1, Hugstetter Str 55, D-79106 Freiburg, Germany. [Gramolini, Anthony O.] Univ Toronto, Dept Physiol, Toronto, ON, Canada. [Byrne, John; Ouzounian, Maral; Husain, Mansoor; Epelman, Slava; Gramolini, Anthony O.; Cybulksky, Myron I.; Rubin, Barry B.; Robbins, Clinton S.] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada. RP Robbins, CS (reprint author), Univ Toronto, Dept Immunol, Toronto, ON, Canada.; Robbins, CS (reprint author), Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.; Robbins, CS (reprint author), Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada. EM clint.robbins@utoronto.ca OI Williams, Jesse/0000-0003-3815-0891 FU Canadian Institutes of Health Research (CIHR) [MSH136670]; CIHR [MOP133390]; Ontario Lung Association/Pfizer Award; Peter Munk Chair in Aortic Disease Research; Ontario Graduate Scholarship FX We acknowledge the administrative assistance of B. Bali. Supported by a Canadian Institutes of Health Research (CIHR) New Investigator Award (MSH136670), a CIHR operating grant (MOP133390), an Ontario Lung Association/Pfizer Award and the Peter Munk Chair in Aortic Disease Research (C.S.R.) and an Ontario Graduate Scholarship (S.E.). NR 45 TC 25 Z9 27 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2016 VL 17 IS 2 BP 159 EP 168 DI 10.1038/ni.3343 PG 10 WC Immunology SC Immunology GA DB5RO UT WOS:000368571500009 PM 26642357 ER PT J AU Khanna, AR Coumans, JV AF Khanna, Arjun R. Coumans, Jean-Valery TI Spontaneous Improvement of Chiari I Malformation and Syringomyelia in a Patient With Cystic Fibrosis: Case Report SO NEUROSURGERY LA English DT Article DE Chiari I malformation; Cystic fibrosis; Syringomyelia; Syrinx; Tonsillar herniation ID OF-THE-LITERATURE; SPONTANEOUS RESOLUTION; PRESSURE; SYRINX; PATHOGENESIS AB BACKGROUND AND IMPORTANCE:Syringomyelia is highly associated with Chiari I malformation, but the pathophysiologic mechanism of syrinx formation and its relation to downward cerebellar tonsillar displacement remains elusive. Cough, Valsalva maneuver, and other physiological strains transiently exacerbate the clinical symptoms of these conditions, exert profound effects on the flow dynamics across the craniospinal junction, and are thought to play an important role in the pathogenesis of syringomyelia.CLINICAL PRESENTATION:We report the case of a patient with cystic fibrosis who presented during an exacerbation of bronchiectasis and was found to have a Chiari I malformation with associated syringomyelia. Eight months later, when the patient had returned to baseline pulmonary status, repeat imaging showed interval improvement in both the size of the syrinx and descent of cerebellar tonsils.CONCLUSION:This rare case of spontaneous improvement of syringomyelia and Chiari I malformation attributable to relief from chronic cough offers interesting insight into the mechanism of these disorders.ABBREVIATIONS:FEV1, forced expiratory volume in 1 secondFVC, forced vital capacity C1 [Khanna, Arjun R.; Coumans, Jean-Valery] Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St, Boston, MA 02114 USA. RP Coumans, JV (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St, Boston, MA 02114 USA. EM jcoumans@partners.org NR 26 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 2016 VL 78 IS 2 BP E305 EP E308 DI 10.1227/NEU.0000000000000980 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DB6BP UT WOS:000368598400001 PM 26308731 ER PT J AU Patel, AV Lane, AM Morrison, MA Trofimov, AV Shih, HA Gragoudas, ES Kim, IK AF Patel, Avni V. Lane, Anne Marie Morrison, Margaux A. Trofimov, Alexei V. Shih, Helen A. Gragoudas, Evangelos S. Kim, Ivana K. TI Visual Outcomes after Proton Beam Irradiation for Choroidal Melanomas Involving the Fovea SO OPHTHALMOLOGY LA English DT Article ID UVEAL MELANOMAS; RADIATION MACULOPATHY; RADIOTHERAPY; THERAPY; TRIAL AB Purpose: To report visual outcomes in patients undergoing proton beam irradiation of tumors located within 1 disc diameter of the fovea. Design: Retrospective review. Participants: Patients with choroidal melanoma involving the fovea treated with proton beam therapy between 1975 and 2009. Methods: Three hundred fifty-one patients with choroidal melanomas located 1 disc diameter (DD) or less from the fovea and more than 1 DD away from the optic nerve were included in this study. In a subgroup of 203 of the patients with small and medium choroidal melanomas, the effect of a reduced dose of radiation, 50 Gy (relative biological effectiveness [RBE]) versus 70 Gy (RBE), on visual outcomes was analyzed. The Kaplan-Meier method and Cox regression analysis were performed to calculate cumulative rates of vision loss and to assess risk factors for vision loss, respectively. Main Outcome Measures: Visual acuity and radiation complications, which included radiation maculopathy, papillopathy, retinal detachment, and rubeosis, were assessed. Results: Three hundred fifty-one patients were included in this study with a mean follow-up time of 68.7 months. More than one-third of patients (35.5%) retained 20/200 or better vision 5 years after proton beam irradiation. For those patients with a baseline visual acuity of 20/40 or better, 16.2% of patients retained this level of vision 5 years after proton beam irradiation. Tumor height less than 5 mm and baseline visual acuity 20/40 or better were associated significantly with a better visual outcome (P < 0.001). More than two-thirds (70.4%) of patients receiving 50 Gy (RBE) and nearly half (45.1%) of patients receiving 70 Gy (RBE) retained 20/200 or better vision 5 years after treatment, but this difference was not significant. Approximately 20% of patients with these smaller macular tumors retained 20/40 vision or better 5 years after irradiation. Conclusions: The results of this retrospective analysis demonstrate that despite receiving a full dose of radiation to the fovea, many patients with choroidal melanoma with foveal involvement maintain useful vision. A radiation dose reduction from 70 to 50 Gy (RBE) did not seem to increase the proportion of patients who retain usable vision. (C) 2016 by the American Academy of Ophthalmology. C1 [Patel, Avni V.; Lane, Anne Marie; Gragoudas, Evangelos S.; Kim, Ivana K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Morrison, Margaux A.] Univ Utah, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA. [Trofimov, Alexei V.; Shih, Helen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Kim, IK (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM ivana_kim@meei.harvard.edu FU Grimshaw-Gudewicz Charitable Foundation (Fall River, MA) FX Supported by the Grimshaw-Gudewicz Charitable Foundation (Fall River, MA). NR 17 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2016 VL 123 IS 2 BP 369 EP 377 DI 10.1016/j.ophtha.2015.09.031 PG 9 WC Ophthalmology SC Ophthalmology GA DB2TK UT WOS:000368362200030 PM 26545316 ER PT J AU Bell, RC Yager, PH Clark, ME Roumiantsev, S Venancio, HL Chipman, DW Kacmarek, RM Noviski, NN AF Bell, Rebecca C. Yager, Phoebe H. Clark, Maureen E. Roumiantsev, Serguei Venancio, Heather L. Chipman, Daniel W. Kacmarek, Robert M. Noviski, Natan N. TI Telemedicine Versus Face-to-Face Evaluations by Respiratory Therapists of Mechanically Ventilated Neonates and Children: A Pilot Study SO RESPIRATORY CARE LA English DT Article DE telemedicine; pediatrics; intensive care; physical examination; reliability of results ID INTENSIVE-CARE-UNIT; ICU TELEMEDICINE; OUTCOMES; PROGRAM AB BACKGROUND: Mechanical ventilation is one of the most important therapeutic interventions in neonatal and pediatric ICUs. Telemedicine has been shown to reliably extend pediatric intensivist expertise to facilities where expertise is limited. If reliable, telemedicine may extend the reach of pediatric respiratory therapists (RTs) to facilities where expertise does not exist or free up existing RT resources for important face-to-face activities in facilities where expertise is limited. The aim of this study was to determine how well respiratory assessments for ventilated neonates and children correlated when performed simultaneously by 2 RTs face-to-face and via telemedicine. METHODS: We conducted a pilot study including 40 assessments by 16 RTs on 11 subjects (5 neonatal ICU; 6 pediatric ICU). Anonymously completed intake forms by 2 different RTs concurrently assessing 14 ventilator-derived and patient-based respiratory variables were used to determine correlations. RESULTS: Forty paired assessments were performed. Median telemedicine assessment time was 8 min. The Pearson correlation coefficient (r) was used to determine agreement between continuous data, and the Cohen kappa statistics were used for binary variables. Pressure control, PEEP, breathing frequency, and F-IO2 perfectly correlated (r = 1, all P < .001) as did the presence of a CO2 monitor and need for increased ventilatory support (kappa = 1). The Pearson correlation coefficient for V-T, minute ventilation, mean airway pressure, and oxygen saturation ranged from 0.84 to 0.97 (all P<.001). kappa = 0.41 (95% CI 0.02-0.80) for patient-triggered breaths, and kappa = 0.57 (95% CI 0.19-0.94) for breathing frequency higher than set frequency. kappa = -0.25 (95% CI -0.46 to -0.04) for need for suctioning. CONCLUSIONS: Telemedicine technology was acceptable to RTs. Telemedicine evaluations highly correlated with face-to-face for 10 of 14 aspects of standard bedside respiratory assessment. Poor correlation was noted for more complex, patient-generated parameters, highlighting the importance of further investigation incorporating a virtual stethoscope. C1 [Bell, Rebecca C.] Univ Vermont, Childrens Hosp, Div Inpatient & Crit Care Pediat, Burlington, VT 05405 USA. [Yager, Phoebe H.; Clark, Maureen E.; Noviski, Natan N.] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Crit Care, Boston, MA 02114 USA. [Roumiantsev, Serguei] Massachusetts Gen Hosp, Dept Pediat, Div Neonatol & Newborn Med, Boston, MA 02114 USA. [Venancio, Heather L.; Chipman, Daniel W.; Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Noviski, NN (reprint author), 175 Cambridge St,CPZS 5, Boston, MA 02114 USA. EM nnoviski@partners.org FU Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; Covidien; Venner Medical FX This work was supported by the Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts. Dr Kacmarek consults for Orange Medical and has received research grants from Covidien and Venner Medical. Drs Bell, Yager, Roumiantsev, Noviski, Ms Clark, Ms Venancio and Mr Chipman have disclosed no conflicts of interest. NR 26 TC 0 Z9 0 U1 1 U2 5 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD FEB PY 2016 VL 61 IS 2 BP 149 EP 154 DI 10.4187/respcare.04080 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DB3LZ UT WOS:000368414400005 PM 26647456 ER PT J AU Nezolosky, MD Dinh, KT Muralidhar, V Mahal, BA Chen, YW Beard, CJ Choueiri, TK Martin, NE Sweeney, CJ Trinh, QD Nguyen, PL AF Nezolosky, Michelle D. Dinh, Kathryn T. Muralidhar, Vinayak Mahal, Brandon A. Chen, Yu-Wei Beard, Clair J. Choueiri, Toni K. Martin, Neil E. Sweeney, Christopher J. Quoc-Dien Trinh Nguyen, Paul L. TI Significant increase in prostatectomy and decrease in radiation for clinical T3 prostate cancer from 1998 to 2012 SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Prostate cancer; Prostatectomy; Radiation therapy; Clinical T3 disease; Treatment patterns ID SEMINAL-VESICLE INVASION; RADICAL PROSTATECTOMY; ADJUVANT RADIOTHERAPY; SINGLE-INSTITUTION; SURVIVAL; OUTCOMES; TRIAL; MEN; RECURRENCE; ADENOCARCINOMA AB Purpose: We aimed to describe changes in treatment patterns for clinical T3 prostate cancer (PCa) from 1998 to 2012, specifically investigating what factors influence receipt of prostatectomy or radiation. Materials and methods: Using the Surveillance, Epidemiology, and End Results database, we studied 11,604 men with clinical T3NOMO PCa from 1998 to 2012, with treatment categorized as radiation, radical prostatectomy (RP), or no curative therapy. We calculated rate of treatment type by year of diagnosis to investigate trends in treatment patterns, further stratifying by clinical T3a, defined as unilateral and bilateral extracapsular extension (n = 3,842), vs. T3b (defined as extension to seminal vesicles (n = 3,665). Finally, a multivariable logistic regression analysis measured association of demographic and clinical variables with type of treatment received for years 2010 to 2011. Results: Rates of prostatectomy increased significantly from 1998 to 2012 (12.5% vs. 44.4%), radiation decreased significantly (55.8% vs. 38.4%), and receipt of no treatment also decreased (31.7% vs. 17.2%, all P < 0.001). These trends were similar for clinical T3a and T3b. Rates of prostatectomy surpassed radiation by 2008 in clinical T3a, reaching 49.8% vs. 37.1%, respectively, in 2012 (P = 0.002), and were statistically similar to radiation in 2012 for clinical T3b, reaching 41.6% vs. 42.1% (P = 0.92). Multivariable logistic regression analysis demonstrated that patients were less likely to receive prostatectomy than radiation if biopsy Gleason scores of 8 to 10 (adjusted odds ratio [AOR] = 0.41, 0.32-0.53), higher initial prostate-specific antigen (AOR = 0.97, 0.97-0.98), and older age (AOR = 0.92, 0.90-0.03, all P < 0.01). The likelihood of RP was similar among cT3b vs. cT3a (AOR = 0.95, 0.71-1.26, P = 0.74). Conclusions: Since 1998, there has been a significant increase in the use of RP for clinical T3 PCa and a significant decrease in the use of radiation such that in 2012, the use of prostatectomy exceeded the use of radiation. (C) 2016 Elsevier Inc. All rights reserved. C1 [Nezolosky, Michelle D.; Beard, Clair J.; Martin, Neil E.; Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Nezolosky, Michelle D.; Beard, Clair J.; Martin, Neil E.; Nguyen, Paul L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dinh, Kathryn T.; Muralidhar, Vinayak; Beard, Clair J.; Choueiri, Toni K.; Martin, Neil E.; Sweeney, Christopher J.; Quoc-Dien Trinh; Nguyen, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. [Mahal, Brandon A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Internal Med, Boston, MA 02115 USA. [Chen, Yu-Wei] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu FU Fitz's Cancer Warriors; Prostate Cancer Foundation; Campbell Family in Honor of Joan Campbell; anonymous family foundation FX This work is supported financially by Fitz's Cancer Warriors, David and Cynthia Chapin, the Prostate Cancer Foundation, Hugh Simons in honor of Frank and Anne Simons, Scott Forbes and Gina Ventre, The Campbell Family in Honor of Joan Campbell, and a grant from an anonymous family foundation. All listed authors were involved in the design, data analysis, and manuscript preparation, and all authors approved the final version of this paper. Paul L. Nguyen has consulted for Medivation and GenomeDX. NR 38 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD FEB PY 2016 VL 34 IS 2 AR 57.e22 DI 10.1016/j.urolonc.2015.09.002 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA DB2HN UT WOS:000368329000009 ER PT J AU Gupta, P Tang, XY Rettiganti, M Lauer, C Kacmarek, RM Rice, TB Markovitz, BP Wetzel, RC AF Gupta, Punkaj Tang, Xinyu Rettiganti, Mallikarjuna Lauer, Casey Kacmarek, Robert M. Rice, Tom B. Markovitz, Barry P. Wetzel, Randall C. TI Association of house staff training with mortality in children with critical illness SO ACTA PAEDIATRICA LA English DT Article DE Children; Critical illness; Fellowship; Intensive care; Mortality ID PEDIATRIC INTENSIVE-CARE; RESIDENT INVOLVEMENT; OUTCOMES; UNITS; COSTS; SURGERY; TESTS; TIMES AB Aim: To evaluate the association of house staff training with mortality in children with critical illness. Methods: Patients <18 years of age in the Virtual PICU Systems (VPS, LLC) Database (2009-2013) were included. The study population was divided in two study groups: hospitals with residency programme only and hospitals with both residency and fellowship programme. Control group constituted hospitals with no residency or fellowship programme. The primary study outcome was mortality before intensive care unit (ICU) discharge. Multivariable logistic regression models were fitted to evaluate association of training programmes with ICU mortality. Results: A total of 336 335 patients from 108 centres were included. Case-mix of patients among the hospitals with training programmes was complex; patients cared for in the hospitals with training programmes had greater severity of illness, had higher resource utilisation and had higher overall admission risk of death compared to patients cared for in the control hospitals. Despite caring for more complex and sicker patients, the hospitals with training programmes were associated with lower odds of ICU mortality. Conclusion: Our study establishes that ICU care provided in hospitals with training programmes is associated with improved adjusted survival rates among the Virtual PICU database hospitals in the United States. C1 [Gupta, Punkaj] Univ Arkansas Med Sci, Dept Pediat, Div Pediat Cardiol, Little Rock, AR 72223 USA. [Tang, Xinyu; Rettiganti, Mallikarjuna] Univ Arkansas Med Sci, Dept Pediat, Biostat Sect, Little Rock, AR 72223 USA. [Lauer, Casey; Rice, Tom B.; Markovitz, Barry P.; Wetzel, Randall C.] Virtual PICU Syst LLC, Los Angeles, CA USA. [Kacmarek, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Rice, Tom B.] Med Coll Wisconsin, Dept Pediat, Div Pediat Crit Care, Milwaukee, WI 53226 USA. [Markovitz, Barry P.; Wetzel, Randall C.] USC, Childrens Hosp Los Angeles, Keck Sch Med, Div Crit Care Med,Dept Pediat & Anesthesiol, Los Angeles, CA USA. RP Gupta, P (reprint author), Univ Arkansas Med Sci, Arkansas Childrens Hosp, Coll Med, Div Pediat Cardiol,Dept Pediat, 1 Childrens Way,Slot 512-3, Little Rock, AR 72223 USA. EM pgupta2@uams.edu NR 20 TC 3 Z9 3 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0803-5253 EI 1651-2227 J9 ACTA PAEDIATR JI Acta Paediatr. PD FEB PY 2016 VL 105 IS 2 BP E60 EP E66 DI 10.1111/apa.13223 PG 7 WC Pediatrics SC Pediatrics GA DA6NK UT WOS:000367921500003 PM 26399703 ER PT J AU McElroy, SL Kemp, DE Friedman, ES Reilly-Harrington, NA Sylvia, LG Calabrese, JR Rabideau, DJ Ketter, TA Thase, ME Singh, V Tohen, M Bowden, CL Bernstein, EE Brody, BD Deckersbach, T Kocsis, JH Kinrys, G Bobo, WV Kamali, M McInnis, MG Leon, AC Faraone, S Nierenberg, AA Shelton, RC AF McElroy, S. L. Kemp, D. E. Friedman, E. S. Reilly-Harrington, N. A. Sylvia, L. G. Calabrese, J. R. Rabideau, D. J. Ketter, T. A. Thase, M. E. Singh, V. Tohen, M. Bowden, C. L. Bernstein, E. E. Brody, B. D. Deckersbach, T. Kocsis, J. H. Kinrys, G. Bobo, W. V. Kamali, M. McInnis, M. G. Leon, A. C. Faraone, S. Nierenberg, A. A. Shelton, R. C. TI Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE bipolar disorder; obesity; metabolic syndrome; outcome ID BODY-MASS INDEX; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; I-DISORDER; 1ST-EPISODE MANIA; LONG-TERM; MEDICAL BURDEN; SYMPTOMS SCALE; REGIONAL GRAY; DSM-IV; OVERWEIGHT AB Objective: Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. Method: The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. Results: At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. Conclusion: Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium-or quetiapine-based treatment. C1 [McElroy, S. L.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [McElroy, S. L.] Lindner Ctr HOPE, Mason, OH USA. [Kemp, D. E.; Calabrese, J. R.] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. [Friedman, E. S.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. [Reilly-Harrington, N. A.; Sylvia, L. G.; Bernstein, E. E.; Deckersbach, T.; Kinrys, G.; Nierenberg, A. A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Reilly-Harrington, N. A.; Sylvia, L. G.; Deckersbach, T.; Kinrys, G.; Nierenberg, A. A.] Harvard Univ, Sch Med, Boston, MA USA. [Rabideau, D. J.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Ketter, T. A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA USA. [Thase, M. E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Singh, V.; Bowden, C. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Tohen, M.] Univ New Mexico, Dept Psychiat, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Brody, B. D.; Kocsis, J. H.; Leon, A. C.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Bobo, W. V.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. [Kamali, M.; McInnis, M. G.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Faraone, S.] SUNY Upstate Med Univ, Dept Psychiat & Neurosci & Physiol, Syracuse, NY 13210 USA. [Shelton, R. C.] Univ Alabama Birmingham, Dept Psychiat, Birmingham, AL USA. RP McElroy, SL (reprint author), Lindner Ctr HOPE, Mason, OH USA. EM susan.mcelroy@lindnercenter.org OI Faraone, Stephen/0000-0002-9217-3982 FU AHRQ [R01 HS019371-01] FX This study was funded by AHRQ Grant R01 HS019371-01. NR 55 TC 2 Z9 2 U1 4 U2 11 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 FEB PY 2016 VL 133 IS 2 BP 144 EP 153 DI 10.1111/acps.12460 PG 10 WC Psychiatry SC Psychiatry GA DA7SE UT WOS:000368003600006 ER PT J AU Stricker, NH Salat, DH Kuhn, TP Foley, JM Price, JS Westlye, LT Esterman, MS McGlinchey, RE Milberg, WP Leritz, EC AF Stricker, Nikki H. Salat, David H. Kuhn, Taylor P. Foley, Jessica M. Price, Jenessa S. Westlye, Lars T. Esterman, Michael S. McGlinchey, Regina E. Milberg, William P. Leritz, Elizabeth C. TI Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE diffusion tensor imaging; magnetic resonance imaging; mild cognitive impairment; corpus callosum; Alzheimer's disease ID ALZHEIMERS-DISEASE; HUMAN BRAIN; TRACT INTEGRITY; DIFFUSION ANISOTROPY; FIBER TRACTOGRAPHY; NERVE-FIBERS; LIFE-SPAN; AGE; MRI; DEMENTIA AB Degenerative brain changes in Alzheimer's disease may occur in reverse order of normal brain development based on the retrogenesis model. This study tested whether evidence of reverse myelination was observed in mild cognitive impairment (MCI) using a data-driven analytic approach based on life span developmental data. Whole-brain high-resolution diffusion tensor imaging scans were obtained for 31 patients with MCI and 79 demographically matched healthy older adults. Comparisons across corpus callosum (CC) regions of interest (ROIs) showed decreased fractional anisotropy (FA) in the body but not in the genu or splenium; early-, middle-, and late-myelinating ROIs restricted to the CC revealed decreased FA in late- but not early- or middle-myelinating ROIs. Voxelwise group differences revealed areas of lower FA in MCI, but whole-brain differences were equally distributed across early-, middle-, and late-myelinating regions. Overall, results within the CC support the retrogenesis model, although caution is needed when generalizing these results beyond the CC. C1 [Stricker, Nikki H.; Kuhn, Taylor P.; Foley, Jessica M.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Stricker, Nikki H.; Esterman, Michael S.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Salat, David H.; Esterman, Michael S.; Leritz, Elizabeth C.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. [Salat, David H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Salat, David H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Foley, Jessica M.; Price, Jenessa S.; McGlinchey, Regina E.; Milberg, William P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Price, Jenessa S.] McLean Hosp, Belmont, MA 02178 USA. [Westlye, Lars T.] Univ Oslo, Norwegian Ctr Mental Disorder Res NORMENT, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict,Oslo Univ Hosp, Oslo, Norway. [Westlye, Lars T.] Univ Oslo, Inst Clin Med, Oslo, Norway. [Westlye, Lars T.] Univ Oslo, Dept Psychol, Oslo, Norway. [McGlinchey, Regina E.; Milberg, William P.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Leritz, Elizabeth C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Stricker, NH (reprint author), VA Boston Med Ctr, 116B,150 S Huntington Ave, Jamaica Plain, MA 02130 USA. EM nikki.stricker@va.gov RI McGlinchey, Regina/R-1971-2016; OI Westlye, Lars T./0000-0001-8644-956X FU Department of Veterans Affairs; Veterans Health Administration; VISN 1 Career Development Award; Gilbert Foundation/AFAR; Medical Research Service VA Merit Review Awards; Veterans Affairs Clinical Science R&D Career Development Award [1IK2CX000706-01A2]; National Institute of Neurologic Disorders and Stroke [K23NS062148]; National Institute of Nursing Research [R01NR010827]; National Institute on Aging [P60AG08812, P01AG004390]; Research Council of Norway [204966/F20]; National Institute on Drug Abuse [2T32DA015036] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Department of Veterans Affairs, Veterans Health Administration, VISN 1 Career Development Award, and the Gilbert Foundation/AFAR. This work was also supported by the Medical Research Service VA Merit Review Awards, Veterans Affairs Clinical Science R&D Career Development Award (1IK2CX000706-01A2), the National Institute of Neurologic Disorders and Stroke (grant number K23NS062148); the National Institute of Nursing Research (grant number R01NR010827), the National Institute on Aging (grant numbers P60AG08812, P01AG004390); the Research Council of Norway (204966/F20), and by the National Institute on Drug Abuse (2T32DA015036). NR 74 TC 3 Z9 3 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 EI 1938-2731 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD FEB PY 2016 VL 31 IS 1 BP 68 EP 75 DI 10.1177/1533317515578257 PG 8 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA DB0CG UT WOS:000368175600008 PM 25904759 ER PT J AU Foley, JM Salat, DH Stricker, NH McGlinchey, RE Milberg, WP Grande, LJ Leritz, EC AF Foley, Jessica M. Salat, David H. Stricker, Nikki H. McGlinchey, Regina E. Milberg, William P. Grande, Laura J. Leritz, Elizabeth C. TI Glucose Dysregulation Interacts With APOE-epsilon 4 to Potentiate Temporoparietal Cortical Thinning SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE APOE-epsilon 4; cortical thickness; aging; Alzheimer's disease; neuroimaging; diabetes ID APOLIPOPROTEIN-E EPSILON-4; MILD COGNITIVE IMPAIRMENT; TENSOR-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; RISK-FACTORS; HIPPOCAMPAL ATROPHY; DIABETES-MELLITUS AB We examined the interactive effects of apolipoprotein 4 (APOE-epsilon 4), a risk factor for Alzheimer's disease (AD), and diabetes risk on cortical thickness among 107 healthy elderly participants; in particular, participants included 27 APOE-epsilon 4+ and 80 APOE-epsilon 4- controls using T1-weighted structural magnetic resonance imaging. Regions of interests included select frontal, temporal, and parietal cortical regions. Among APOE-epsilon 4, glucose abnormalities independently predicted reduced cortical thickness among temporoparietal regions but failed to predict changes for noncarriers. However, among noncarriers, age independently predicted reduced cortical thickness among temporoparietal and frontal regions. Diabetes risk is particularly important for the integrity of cortical gray matter in APOE-epsilon 4 and demonstrates a pattern of thinning that is expected in preclinical AD. However, in the absence of this genetic factor, age confers risk for reduced cortical thickness among regions of expected compromise. This study supports aggressive management of cerebrovascular factors and earlier preclinical detection of AD among individuals presenting with genetic and metabolic risks. C1 [Foley, Jessica M.; Salat, David H.; Stricker, Nikki H.; McGlinchey, Regina E.; Milberg, William P.; Grande, Laura J.; Leritz, Elizabeth C.] VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. [Foley, Jessica M.; Salat, David H.; McGlinchey, Regina E.; Milberg, William P.; Leritz, Elizabeth C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Foley, Jessica M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. [Salat, David H.; Milberg, William P.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Stricker, Nikki H.; Grande, Laura J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Foley, JM (reprint author), Univ Calif San Francisco, Med Ctr, Dept Neurol, 1500 Owens St, San Francisco, CA 94158 USA. EM jessica.foley@ucsf.edu RI McGlinchey, Regina/R-1971-2016 FU National Institute of Neurologic Disorders and Stroke [K23NS062148, R01NS086882]; National Institute of Nursing Research [R01NS086882, R01NR010827]; National Institute on Aging [P60AG08812, P01AG004390]; American Psychological Association Division 40; Rosalind and Arthur Gilbert Foundation/AFAR New Investigator Award in Alzheimer's Disease; Medical Research Service VA Merit Review Awards FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute of Neurologic Disorders and Stroke (K23NS062148 and R01NS086882), the National Institute of Nursing Research (R01NR010827 and R01NS086882), the National Institute on Aging (P60AG08812 and P01AG004390), American Psychological Association Division 40, The Rosalind and Arthur Gilbert Foundation/AFAR New Investigator Award in Alzheimer's Disease, and by Medical Research Service VA Merit Review Awards to William Milberg and Regina McGlinchey. NR 73 TC 0 Z9 0 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 EI 1938-2731 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD FEB PY 2016 VL 31 IS 1 BP 76 EP 86 DI 10.1177/1533317515587084 PG 11 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA DB0CG UT WOS:000368175600009 PM 26006791 ER PT J AU Iezzoni, LI Kurtz, SG Rao, SR AF Iezzoni, Lisa I. Kurtz, Stephen G. Rao, Sowmya R. TI Trends in Pap Testing Over Time for Women With and Without Chronic Disability SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PREVENTIVE SERVICES; PHYSICAL-DISABILITIES; MOBILITY IMPAIRMENTS; HEALTH-CARE; BREAST; RECEIPT; ACCESS; LEVEL AB Introduction: Data from 20 years ago-shortly after passage of the Americans with Disabilities Act -showed that women with significant mobility disability had 40% lower Pap test rates than other women. Methods: To examine whether disability disparities in Pap test rates have diminished over time, this study analyzed National Health Interview Survey responses from selected years between 1998 and 2010 from women aged 21-65 years without histories of cervical cancer or hysterectomy. Seven chronic disability types were identified using self-reported functional impairments or participation limitations. Self-reported Pap testing within the previous 3 years was studied. Bivariable analyses and multivariable logistic regression analyses controlling for sociodemographic variables were conducted in 2014. Results: Rates of all chronic disability types increased over time. Pap test rates remained relatively constant over time for all women, holding around 84%-87%. Bivariable analyses found statistically significantly lower rates of Pap testing for women with disability compared with nondisabled women. Multivariable analyses failed to find consistent evidence of lower Pap test rates among women across disability types compared with nondisabled women. In 2010, the AOR for reporting Pap testing for women noting the most severe movement difficulty compared with nondisabled women was 0.35 (95% CI = 0.15, 0.79). However, the AOR for this disability type varied over time. Conclusions: Little has changed over time in Pap test rates for all women. Women with certain disabilities continue to experience disparities compared with nondisabled women in receipt of this important screening test. (C) 2016 American Journal of Preventive Medicine C1 [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kurtz, Stephen G.; Rao, Sowmya R.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Rao, Sowmya R.] Bedford Vet Affairs Med Ctr, CHOIR, Bedford, MA USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@mgh.harvard.edu FU National Cancer Institute [5 R01 CA160286-02] FX This work was funded by the National Cancer Institute, 5 R01 CA160286-02. NR 32 TC 1 Z9 1 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD FEB PY 2016 VL 50 IS 2 BP 210 EP 219 DI 10.1016/j.amepre.2015.06.031 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA DB1DG UT WOS:000368247600014 PM 26372417 ER PT J AU McGrath, JM Fisher, V Krejci-Manwaring, J AF McGrath, John M. Fisher, Valerie Krejci-Manwaring, Jennifer TI Skin Cancer Warnings and the Need for New Preventive Campaigns A Pilot Study SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID PREVALENCE C1 [McGrath, John M.] Trinity Univ, Dept Human Commun, San Antonio, TX 78212 USA. [McGrath, John M.; Krejci-Manwaring, Jennifer] Audie L Murphy Vet Hosp, San Antonio, TX USA. [Fisher, Valerie; Krejci-Manwaring, Jennifer] Univ Texas Hlth Sci Ctr San Antonio, Div Dermatol & Cutaneous Surg, San Antonio, TX 78229 USA. RP McGrath, JM (reprint author), Trinity Univ, Dept Human Commun, One Trinity Pl, San Antonio, TX 78212 USA. EM jmcgrath@trinity.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD FEB PY 2016 VL 50 IS 2 BP E62 EP E63 DI 10.1016/j.amepre.2015.10.009 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA DB1DG UT WOS:000368247600004 PM 26657182 ER PT J AU Acosta, DC Loehrer, A Chang, DC AF Acosta, D. C. Loehrer, A. Chang, D. C. TI Nativity Status Negatively Impacts Quality of Breast Cancer Care for Latinos in the U.S SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Acosta, D. C.; Loehrer, A.; Chang, D. C.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P21 BP S52 EP S52 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000126 ER PT J AU Berger, ER Kinnier, CV Minami, CA Winchester, DP Yang, AD Bilimoria, K AF Berger, E. R. Kinnier, C. V. Minami, C. A. Winchester, D. P. Yang, A. D. Bilimoria, K. TI Hospital Level Adjusted Sentinel Lymph Node Positivity Rates in Breast Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Berger, E. R.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Minami, C. A.; Yang, A. D.; Bilimoria, K.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Kinnier, C. V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Winchester, D. P.] Northshore Univ HealthSyst, Dept Surg, Evanston, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P1 BP S47 EP S47 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000108 ER PT J AU Chan, CH Liesenfeld, L Ferreiro-Neira, I Cusack, JC AF Chan, C. H. Liesenfeld, L. Ferreiro-Neira, I. Cusack, J. C. TI Detecting Peritoneal Surface Malignancies with Cathepsin-Based Fluorescent Imaging System SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Chan, C. H.; Liesenfeld, L.; Ferreiro-Neira, I.; Cusack, J. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P127 BP S88 EP S88 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000231 ER PT J AU Cintolo-Gonzalez, JA Hammond, M Frederick, D Lawrence, N Piris, A Flaherty, K Wargo, J Cooper, Z Hoang, M Kwong, L Boland, G AF Cintolo-Gonzalez, J. A. Hammond, M. Frederick, D. Lawrence, N. Piris, A. Flaherty, K. Wargo, J. Cooper, Z. Hoang, M. Kwong, L. Boland, G. TI Predicting Response to BRAF-Targeted Therapy Using an Immune Signature SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Cintolo-Gonzalez, J. A.; Hammond, M.; Frederick, D.; Lawrence, N.; Flaherty, K.; Hoang, M.; Boland, G.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Piris, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wargo, J.; Cooper, Z.; Kwong, L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P239 BP S123 EP S123 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000334 ER PT J AU Datta, J Cintolo-Gonzalez, JA Ellingsworth, C Xu, S Lowenfeld, L Berk, E Somasundaram, R Czerniecki, BJ AF Datta, J. Cintolo-Gonzalez, J. A. Ellingsworth, C. Xu, S. Lowenfeld, L. Berk, E. Somasundaram, R. Czerniecki, B. J. TI A Novel Dendritic Cell Vaccine Targeting Mutated BRAF Overcomes Vemurafenib Resistance and Synergistically Improves Survival in BRAF-Mutant Murine Melanoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Datta, J.; Xu, S.; Lowenfeld, L.; Berk, E.; Czerniecki, B. J.] Univ Penn, Surg, Philadelphia, PA 19104 USA. [Ellingsworth, C.; Somasundaram, R.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Cintolo-Gonzalez, J. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA 66 BP S31 EP S31 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000067 ER PT J AU Epstein, J Kozak, G Fong, Z Jiang, W Lavu, H Ferrone, CR Lillemoe, K Yeo, C Fernandez-del Castillo, C Winter, J AF Epstein, J. Kozak, G. Fong, Z. Jiang, W. Lavu, H. Ferrone, C. R. Lillemoe, K. Yeo, C. Fernandez-del Castillo, C. Winter, J. TI Lymphovascular Invasion: An Underappreciated Prognostic Factor in Pancreatic Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Epstein, J.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Kozak, G.; Lavu, H.; Yeo, C.; Winter, J.] Thomas Jefferson Univ Hosp, Dept Surg, Philadelphia, PA 19107 USA. [Fong, Z.; Ferrone, C. R.; Lillemoe, K.; Fernandez-del Castillo, C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Jiang, W.] Thomas Jefferson Univ Hosp, Dept Pathol, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P385 BP S172 EP S172 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000477 ER PT J AU Fong, Z Mehtsun, W Lillemoe, K Warshaw, A Fernandez-del Castillo, C Chang, DC Ferrone, CR AF Fong, Z. Mehtsun, W. Lillemoe, K. Warshaw, A. Fernandez-del Castillo, C. Chang, D. C. Ferrone, C. R. TI The Role of Staging Laparoscopy in Patients with Pancreatic Adenocarcinoma: Withstanding the Test of Time? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Fong, Z.; Mehtsun, W.; Lillemoe, K.; Warshaw, A.; Fernandez-del Castillo, C.; Chang, D. C.; Ferrone, C. R.] Massachusetts Gen Hosp, Surg, Natick, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P384 BP S171 EP S172 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000476 ER PT J AU Loehrer, A Chang, DC Song, Z Hutter, MM Mullen, JT AF Loehrer, A. Chang, D. C. Song, Z. Hutter, M. M. Mullen, J. T. TI Impact of Insurance Expansion on Access to Colorectal Cancer Care SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Loehrer, A.; Chang, D. C.; Song, Z.; Hutter, M. M.; Mullen, J. T.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA 37 BP S20 EP S20 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000038 ER PT J AU Mehtsun, W Fong, Z Del Castillo, CF Hemingway, K Lillemoe, K Warshaw, A Chang, DC Ferrone, CR AF Mehtsun, W. Fong, Z. Del Castillo, C. Fernandez Hemingway, K. Lillemoe, K. Warshaw, A. Chang, D. C. Ferrone, C. R. TI Indeterminate Nodules in Pancreatic Adenocarcinoma: Are CT Scans of the Chest Necessary? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Mehtsun, W.; Fong, Z.; Del Castillo, C. Fernandez; Hemingway, K.; Lillemoe, K.; Warshaw, A.; Chang, D. C.; Ferrone, C. R.] Massachusetts Gen Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P377 BP S169 EP S169 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000469 ER PT J AU Nurudeen, S Chun, Y Guo, H Barry, W Coopey, SB Garber, JE Dominici, LS AF Nurudeen, S. Chun, Y. Guo, H. Barry, W. Coopey, S. B. Garber, J. E. Dominici, L. S. TI Patient Experience with Breast Reconstruction Following Bilateral Mastectomy in BRCA Mutation Carriers SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Dominici, L. S.] Dana Farber Brigham & Womens Canc Ctr, Surg Oncol, Boston, MA USA. [Nurudeen, S.; Chun, Y.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Guo, H.; Barry, W.; Garber, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Coopey, S. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P81 BP S72 EP S73 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000185 ER PT J AU Plichta, JK Coopey, SB Queiroz, PD Specht, MC Smith, BL Gadd, MA Mazzola, E Parmigiani, G Garber, JE Guidi, AJ Roche, CA Hughes, KS AF Plichta, J. K. Coopey, S. B. Queiroz, P. De Moura Specht, M. C. Smith, B. L. Gadd, M. A. Mazzola, E. Parmigiani, G. Garber, J. E. Guidi, A. J. Roche, C. A. Hughes, K. S. TI The Utility of Screening MRI for Women Diagnosed with Atypical Breast Lesions SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Plichta, J. K.; Coopey, S. B.; Queiroz, P. De Moura; Specht, M. C.; Smith, B. L.; Gadd, M. A.; Roche, C. A.; Hughes, K. S.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Mazzola, E.; Parmigiani, G.; Garber, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Guidi, A. J.] Newton Wellesley Hosp, Newton, MA USA. RI Plichta, Jennifer/L-5450-2016 OI Plichta, Jennifer/0000-0002-7411-0558 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P77 BP S71 EP S71 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000181 ER PT J AU Smalley, R Collura, C Miller, C Berger, D Tanabe, K Ferrone, CR AF Smalley, R. Collura, C. Miller, C. Berger, D. Tanabe, K. Ferrone, C. R. TI With Modern Chemotherapy Prognostic Models Underestimate Which Patients May Benefit from Hepatic Resection for Colorectal Liver Metastases SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Smalley, R.; Miller, C.] Harvard Univ, Sch Med, Boston, MA USA. [Collura, C.; Berger, D.; Tanabe, K.; Ferrone, C. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P180 BP S102 EP S102 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000277 ER PT J AU Williams, R Sich, N Wang, J Pezzi, C Clancy, T Ashley, S Swanson, R AF Williams, R. Sich, N. Wang, J. Pezzi, C. Clancy, T. Ashley, S. Swanson, R. TI Palliative Pancreaticoduodenectomy for Metastatic Pancreatic Adenocarcinoma is Associated with Excessive Postoperative Mortality SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Williams, R.; Wang, J.; Clancy, T.; Ashley, S.; Swanson, R.] Dana Farber Partners Canc Care, Surg Oncol, Boston, MA USA. [Sich, N.; Pezzi, C.] Abington Jefferson Hlth, Abington, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P370 BP S167 EP S167 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000463 ER PT J AU Williams, R Sich, N Clancy, T Wang, J Pezzi, C Ashley, S Swanson, R AF Williams, R. Sich, N. Clancy, T. Wang, J. Pezzi, C. Ashley, S. Swanson, R. TI Pancreaticoduodenectomy for Metastatic Pancreatic Neuroendocrine Tumor SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Williams, R.; Clancy, T.; Wang, J.; Ashley, S.; Swanson, R.] Dana Farber Partners Canc Care, Surg Oncol, Boston, MA USA. [Sich, N.; Pezzi, C.] Abington Jefferson Hlth, Abington, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P367 BP S166 EP S167 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000460 ER PT J AU Wong, SM Freedman, RA Sagara, Y Aydogan, F Barry, WT Golshan, M AF Wong, S. M. Freedman, R. A. Sagara, Y. Aydogan, F. Barry, W. T. Golshan, M. TI Contralateral Prophylactic Mastectomy: Becoming the New Norm Despite a Paucity of Evidence Indicating Survival Benefit? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 69th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 02-05, 2016 CL Boston, MA SP Soc Surg Oncol C1 [Wong, S. M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Freedman, R. A.; Barry, W. T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sagara, Y.; Aydogan, F.; Golshan, M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2016 VL 23 SU 1 MA P9 BP S48 EP S49 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA DB0FW UT WOS:000368185000114 ER PT J AU Holmes, DR Nishimura, RA Grover, FL Brindis, RG Carroll, JD Edwards, FH Peterson, ED Rumsfeld, JS Shahian, DM Thourani, VH Tuzcu, EM Vemulapalli, S Hewitt, K Michaels, J Fitzgerald, S Mack, MJ AF Holmes, David R., Jr. Nishimura, Rick A. Grover, Frederick L. Brindis, Ralph G. Carroll, John D. Edwards, Fred H. Peterson, Eric D. Rumsfeld, John S. Shahian, David M. Thourani, Vinod H. Tuzcu, E. Murat Vemulapalli, Sreekanth Hewitt, Kathleen Michaels, Joan Fitzgerald, Susan Mack, Michael J. CA STS ACC TVT Registry TI Annual Outcomes With Transcatheter Valve Therapy: From the STS/ACC TVT Registry SO ANNALS OF THORACIC SURGERY LA English DT Article ID CITY CARDIOMYOPATHY QUESTIONNAIRE; END-POINT DEFINITIONS; VASCULAR COMPLICATIONS; UNITED-STATES; HEALTH-STATUS; IMPLANTATION; REPLACEMENT; SURVEILLANCE; PACEMAKER; INFRASTRUCTURE AB Background. The Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry has been a joint initiative of the STS and the ACC in concert with multiple stake-holders. The TVT Registry has important information regarding patient selection, delivery of care, science, education, and research in the field of structural valvular heart disease. Objectives. This report provides an overview on current U.S. TVT practice and trends. The emphasis is on demographics, in-hospital procedural characteristics, and outcomes of patients having transcatheter aortic valve replacement (TAVR) performed at 348 U.S. centers. Methods. The TVT Registry captured 26,414 TAVR procedures as of December 31, 2014. Temporal trends between 2012 and 2013 versus 2014 were compared. Results. Comparison of the 2 time periods reveals that TAVR patients remain elderly (mean age 82 years), with multiple comorbidities, reflected by a high mean STS predicted risk of mortality (STS PROM) for surgical valve replacement (8.34%), were highly symptomatic (New York Heart Association functional class III/IV in 82.5%), frail (slow 5-m walk test in 81.6%), and have poor self-reported health status (median baseline Kansas City Cardiomyopathy Questionnaire score of 39.1). Procedure performance is changing, with an increased use of moderate sedation (from 1.6% to 5.1%) and increase in femoral access using percutaneous techniques (66.8% in 2014). Vascular complication rates are decreasing (from 5.6% to 4.2%), whereas site-reported stroke rates remain stable at 2.2%. Conclusions. The TVT Registry provides important information on characteristics and outcomes of TAVR in contemporary U.S. clinical practice. It can be used to identify trends in practice and opportunities for quality improvement. (C) 2016 by The Society of Thoracic Surgeons and the American College of Cardiology Foundation C1 [Holmes, David R., Jr.] Mayo Clin, Rochester, MN 55905 USA. Univ Colorado, Denver, CO 80202 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Florida, Jacksonville, FL USA. Duke Univ, Med Ctr, Durham, NC USA. Denver VA Med Ctr, Denver, CO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Atlanta, GA 30322 USA. Cleveland Clin, Cleveland, OH 44106 USA. Amer Coll Cardiol, Washington, DC USA. Baylor Scott & White Hlth, Plano, TX USA. RP Holmes, DR (reprint author), Mayo Clin, 200 First St Southwest, Rochester, MN 55905 USA. EM holmes.david@mayo.edu FU Edwards Lifesciences; Abbott Vascular; Direct Flow; Janssen; Eli Lily; Boehringer Ingelheim; Bayer; AstraZeneca; Boston Scientific; Philips Medical Systems FX A current list of STS/ACC TVT Registry participating hospitals can be found at https://www.ncdr.com/TVT/Private/Resources/ParticipantDirectory.aspx. Dr Grover has served as a consultant to Somalution; and is the vice chair of the STS/ACC/TVT Registry Steering Committee. Dr Brindis is a senior medical officer for the National Cardiovascular Data Registry. Dr Carroll has served as an investigator in research trials sponsored by Edwards Lifesciences, Abbott Vascular, and Direct Flow. Dr Peterson has received grants from Janssen and Eli Lily; has received personal fees from Janssen, Eli Lilly, Boehringer Ingelheim, Bayer, and AstraZeneca; and has received consulting support from Merck and Sanofi. Dr Rumsfeld is chief science officer for the National Cardiovascular Data Registry. Dr Thourani is an advisor for Edwards Lifesciences; and conducts research for Edwards Lifesciences and Medtronic. Dr Vemulapalli has received research grant support from Boston Scientific; has received funding for travels from Abbott Vascular; and received payment for travel from Philips Medical Systems. Dr Mack is a member of the Executive Committee of the PARTNER Trial, sponsored by Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Raj Makkar, MD, served as Guest Editor for this paper. NR 22 TC 6 Z9 6 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2016 VL 101 IS 2 BP 789 EP 800 DI 10.1016/j.athoracsur.2015.10.049 PG 12 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DB0HR UT WOS:000368189700092 PM 27175453 ER PT J AU Banks, WA Dohi, K Hansen, K Thompson, HJ AF Banks, William A. Dohi, Kenji Hansen, Kim Thompson, Hilaire J. TI Assessing blood granulocyte colony-stimulating factor as a potential biomarker of acute traumatic brain injury in mice and humans SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE G-CSF; Traumatic brain injury; Biomarker; Neuroinflammation; Blood brain barrier ID INTRACEREBROVENTRICULAR INJECTION; SEVERITY SCORE; RATS; INTERLEUKIN-1-BETA; CYTOKINES; BARRIER; IMMUNE; MODEL; CARE AB Previous work has found that serum G-CSF was acutely elevated in mice 24 h but not one week after controlled cortical impact (CCI). The purpose of this study was to investigate whether blood G-CSF correlates with the elevated brain cytokines in mice after CCI and also if it correlates with traumatic brain injury (TBI) in humans. Here, we found in mice undergoing CCI, a procedure that induces direct injury to the brain, that serum G-CSF correlated directly or indirectly with several brain cytokines, indicating it is a useful marker for the neuroinflammation of TBI. A pilot study in humans (phase I, n = 19) confirmed that plasma G-CSF is acutely elevated on day I (p < 0.001) of TBI and has returned to baseline by one week. In a second human sample (phase II) (n = 80), we found plasma G-CSF peaks about 12 h after arriving in the emergency department (41.6 +/ 5.4 pg/ml). Aging was weakly associated (p < 0.05) with a less robust elevation in serum G-CSF, but there was no difference with gender. ISS, a measure of total severity of injury, correlated with the degree of elevation in serum G-CSF (r = .419; p < 0.05), but severity of head injury (via AIS) did not. The latter may have been because of the statistically narrow range of head injuries among our cases and the high number of cases diagnosed with closed head injury (a non-codable diagnosis). In conclusion, plasma G-CSF may be a useful biomarker of TBI, correlating with neuroinflammation in the animal model and in the human studies with time since injury and total severity of injury. As such, it may be useful in determining whether TBI has occurred within the last 24 h. Published by Elsevier Inc. C1 [Banks, William A.; Dohi, Kenji; Hansen, Kim; Thompson, Hilaire J.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Banks, William A.; Dohi, Kenji; Hansen, Kim] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. [Dohi, Kenji] Jikei Univ, Sch Med, Dept Emergency Med, Tokyo, Japan. [Thompson, Hilaire J.] Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Thompson, Hilaire J.] Univ Washington, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA. RP Banks, WA (reprint author), VAPSHCS, Rm 1-810A,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu; kdoppy@jikei.ac.jp; nesnah@u.washington.edu; hilairet@uw.edu FU National Institutes of Health, National Center for Research Resources [KL2RR025015]; National Institute of Neurologic Diseases and Stroke [R01NS077913]; Department of Veterans Affairs; National Institute on Aging [R01AG029839, R01AG046619] FX Supported by grants from the National Institutes of Health, National Center for Research Resources KL2RR025015 (HT), the National Institute of Neurologic Diseases and Stroke R01NS077913 (HT), the Department of Veterans Affairs (WAB), and the National Institute on Aging R01AG029839 (WAB) and R01AG046619 (WAB). NR 30 TC 1 Z9 1 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 EI 1090-2139 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD FEB PY 2016 VL 52 BP 81 EP 87 DI 10.1016/j.bbi.2015.10.002 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA DB2DB UT WOS:000368317400011 PM 26441136 ER PT J AU Ring, D Jawa, A Cannada, L AF Ring, David Jawa, Andrew Cannada, Lisa TI Clinical Faceoff: Are Distal-third Diaphyseal Humerus Fractures Best Treated Nonoperatively? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Editorial Material C1 [Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Jawa, Andrew] Boston Univ, Dept Orthopaed, Boston, MA 02215 USA. [Cannada, Lisa] St Louis Univ, Dept Orthopaed Surg, St Louis, MO 63103 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 4 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2016 VL 474 IS 2 BP 310 EP 314 DI 10.1007/s11999-015-4636-8 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DA7YQ UT WOS:000368021900007 PM 26584799 ER PT J AU Healy, WL Iorio, R Clair, AJ Pellegrini, VD Della Valle, CJ Berend, KR AF Healy, William L. Iorio, Richard Clair, Andrew J. Pellegrini, Vincent D. Della Valle, Craig J. Berend, Keith R. TI Complications of Total Hip Arthroplasty: Standardized List, Definitions, and Stratification Developed by The Hip Society SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID KNEE ARTHROPLASTY; CLASSIFICATION AB Reporting of complications after total hip arthroplasty (THA) is not standardized, and it is done inconsistently across various studies on the topic. Advantages of standardizing complications include improved patient safety and outcomes and better reporting in comparative studies. The purpose of this project was to develop a standardized list of complications and adverse events associated with THA, develop standardized definitions for each complication, and stratify the complications. A further purpose was to validate these standardized THA complications. The Hip Society THA Complications Workgroup proposed a list of THA complications, definitions for each complication, and a stratification scheme for the complications. The stratification system was developed from a previously validated grading system for complications of hip preservation surgery. The proposed complications, definitions, and stratification were validated with an expert opinion survey of members of The Hip Society, a case study evaluation, and analysis of a large administrative hospital system database with a focus on readmissions. One hundred five clinical members (100%) of The Hip Society responded to the THA complications survey. Initially, 21 THA complications were proposed. The validation process reduced the 21 proposed complications to 19 THA complications with definitions and stratification that were endorsed by The Hip Society (bleeding, wound complication, thromboembolic disease, neural deficit, vascular injury, dislocation/instability, periprosthetic fracture, abductor muscle disruption, deep periprosthetic joint infection, heterotopic ossification, bearing surface wear, osteolysis, implant loosening, cup-liner dissociation, implant fracture, reoperation, revision, readmission, death). Acceptance and use of these standardized, stratified, and validated THA complications and adverse events could advance reporting of outcomes of THA and improve assessment of THA by clinical investigators. Level V, therapeutic study. C1 [Healy, William L.] Newton Wellesley Hosp, Kaplan Joint Ctr, Newton, MA 02462 USA. [Healy, William L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Iorio, Richard; Clair, Andrew J.] NYU, Langone Med Ctr, New York, NY USA. [Pellegrini, Vincent D.] Med Univ S Carolina, Charleston, SC 29425 USA. [Della Valle, Craig J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Berend, Keith R.] Joint Implant Surgeons, New Albany, OH USA. RP Healy, WL (reprint author), Newton Wellesley Hosp, Kaplan Joint Ctr, 2014 Washington St, Newton, MA 02462 USA. EM whealy@partners.org OI Iorio, Richard/0000-0001-8083-8687 NR 10 TC 2 Z9 2 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2016 VL 474 IS 2 BP 357 EP 364 DI 10.1007/s11999-015-4341-7 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DA7YQ UT WOS:000368021900015 PM 26040966 ER PT J AU Huddleston, JI Tetreault, MW Yu, M Bedair, H Hansen, VJ Choi, HR Goodman, SB Sporer, SM Della Valle, CJ AF Huddleston, James I., III Tetreault, Matthew W. Yu, Michael Bedair, Hany Hansen, Viktor J. Choi, Ho-Rim Goodman, Stuart B. Sporer, Scott M. Della Valle, Craig J. TI Is There a Benefit to Modularity in 'Simpler' Femoral Revisions? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; POROUS-COATED STEMS; FOLLOW-UP; KNEE ARTHROPLASTY; BONE INGROWTH; COMPONENTS AB Modular revision femoral components allow the surgeon to make more precise intraoperative adjustments in anteversion and sizing, which may afford lower dislocation rates and improved osseointegration, but may not offer distinct advantages when compared with less expensive monoblock revision stems. We compared modular and monoblock femoral components for revision of Paprosky Type I to IIIA femoral defects to determine (1) survivorship of the stems; and (2) complications denoted as intraoperative fracture, dislocation, or failure of osseointegration. Between 2004 and 2010, participating surgeons at three centers revised 416 total hip arthroplasties (THAs) with Paprosky Type I to IIIA femoral defects. Of those with minimum 2-year followup (343 THAs, mean followup 51 +/- 13 months), 150 (44%) were treated with modular stems and 193 (56%) were treated with monoblock, cylindrical, fully porous-coated stems. During this time, modular stems were generally chosen when there was remodeling of the proximal femur into retroversion and/or larger canal diameters (usually > 18 mm). A total of 27 patients died (6%) with stems intact before 2 years, 46 THAs (13%) were lost to followup before 2 years for reasons other than death, and there was no differential loss to followup between the study groups. The modular stems included 101 with a cylindrical distal geometry (67%) and 49 with a tapered geometry (33%). Mean age (64 versus 68 years), percentage of women (53% versus 47%), and body mass index (31 versus 30 kg/m(2)) were not different between the two cohorts, whereas there was trend toward a slightly greater case complexity in the modular group (55% versus 65% Type 3a femoral defects, p = 0.06). Kaplan-Meier survivorship was calculated for the endpoint of aseptic revision. Proportions of complications in each cohort (dislocation, intraoperative fracture, and failure of osseointegration) were compared. Femoral component rerevision for any reason (including infection) was greater (OR, 2.01; 95% CI, 1.63-2.57; p = 0.03) in the monoblock group (27 of 193 [14%]) compared with the modular cohort (10 of 150 [7%]). Femoral component survival free from aseptic rerevision was greater in the modular group with 91% survival (95% CI, 89%-95%) at 9 years compared with 86% survival (95% CI, 83%-88%) for the monoblock group in the same timeframe. There was no difference in the proportion of mechanically relevant aseptic complications (30 of 193 [16%] in the monoblock group versus 34 of 150 [23%] in the modular group, p = 0.10; OR, 1.47; 95% CI, 0.86-2.53). There were more intraoperative fractures in the modular group (17 of 150 [11%] versus nine of 193 [5%]; OR, 2.2; 95% CI, 1.68-2.73; p = 0.02). There were no differences in the proportions of dislocation (13 of 193 [7%] monoblock versus 14 of 150 [9%] modular; OR, 0.96; 95% CI, 0.67-1.16; p = 0.48) or failure of osseointegration (eight of 193 [4%] monoblock versus three of 150 [2%] modular; OR, 1.92; 95% CI, 0.88-2.84; p = 0.19) between the two groups with the number of hips available for study. Although rerevisions were less common in patients treated with modular stems, aseptic complications such as intraoperative fractures were more common in that group, and the sample was too small to evaluate corrosion-related or fatigue concerns associated with modularity. We cannot therefore conclude from this that one design is superior to the other. Larger studies and pooled analyses will need to be performed to answer this question, but we believe modularity should be avoided in more straightforward cases if possible. Level III, therapeutic study. C1 [Huddleston, James I., III; Yu, Michael; Goodman, Stuart B.] Stanford Univ, Sch Med, Dept Orthopaed Surg, Stanford, CA 94305 USA. [Tetreault, Matthew W.; Sporer, Scott M.; Della Valle, Craig J.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. [Bedair, Hany; Hansen, Viktor J.; Choi, Ho-Rim] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthoped Lab, Boston, MA 02114 USA. [Huddleston, James I., III] Stanford Med Outpatient Ctr, Dept Orthopaed Surg, Redwood City, CA 94063 USA. RP Huddleston, JI (reprint author), Stanford Med Outpatient Ctr, Dept Orthopaed Surg, 450 Broadway St,MC 6342, Redwood City, CA 94063 USA. EM jhuddleston@stanford.edu OI Tetreault, Matthew/0000-0003-3584-9285 NR 20 TC 2 Z9 2 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2016 VL 474 IS 2 BP 415 EP 420 DI 10.1007/s11999-015-4474-8 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DA7YQ UT WOS:000368021900025 PM 26245164 ER PT J AU Menendez, ME Ring, D AF Menendez, Mariano E. Ring, David TI Emergency Department Visits After Hand Surgery Are Common and Usually Related to Pain or Wound Issues SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ACUTE-CARE; ADMINISTRATIVE DATA; ORTHOPEDIC-SURGERY; COMORBIDITY INDEX; DISCHARGE; READMISSION; ICD-9-CM AB As payment models shift toward a focus on value and reimbursement becomes increasingly tied to quality and patient experience, minimizing unexpected acute health needs has become a priority for both policymakers and clinical leaders. Despite recent emphasis on emergency department (ED) visits as a quality measure in surgery, little is known about the role of the ED in the early postoperative period after hand surgery. The purpose of this study was to determine the rates, reasons, and factors associated with ED visits within 30 days of elective outpatient hand surgery. Using our institutional database for 2009 through 2013, we assessed ED visit rates for 2332 patients undergoing carpal tunnel or trigger finger release. Medical records were manually reviewed to ascertain the primary reason for the ED visit. Multivariable logistic regression modeling was used to identify factors independently associated with ED use. A total of 67 patients (3%) experienced at least one ED visit within 30 days of hand surgery (carpal tunnel: 3%; trigger finger: 3%). Most visits (66%) occurred within the first 2 weeks of surgery, and 31% led to hospitalization. The most common reasons for ED visits were pain (18%) and wound issues (16%). Unmarried and medically infirm patients were more likely to visit the ED. ED visits after hand surgery are common, often related to the procedure, and potentially responsive to quality improvement initiatives. Targeted efforts to educate patients about pain management, wound care, and the expected course of recovery before surgery, together with close postoperative contact (eg, routine phone calls, facsimile correspondence by email, or secure messaging) may limit visits to the ED. Level IV, prognostic study. C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM marianofurrer@gmail.com NR 20 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2016 VL 474 IS 2 BP 551 EP 556 DI 10.1007/s11999-015-4489-1 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DA7YQ UT WOS:000368021900046 PM 26245167 ER PT J AU Claessen, FMAP Braun, Y van Leeuwen, WF Dyer, GS van den Bekerom, MPJ Ring, D AF Claessen, Femke M. A. P. Braun, Yvonne van Leeuwen, Wouter F. Dyer, George S. van den Bekerom, Michel P. J. Ring, David TI What Factors are Associated With a Surgical Site Infection After Operative Treatment of an Elbow Fracture? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PERIPROSTHETIC JOINT INFECTION; PROXIMAL HUMERAL FRACTURES; RISK-FACTORS; SMOKING-CESSATION; ORTHOPEDIC PATIENTS; TIBIA FRACTURES; SHAFT FRACTURES; COMPLICATIONS; SURGERY; PREVENTION AB Surgical site infections are one of the more common major complications of elbow fracture surgery and can contribute to other adverse outcomes, prolonged hospital stays, and increased healthcare costs. We asked: (1) What are the factors associated with a surgical site infection after elbow fracture surgery? (2) When taking the subset of closed elbow fractures only, what are the factors associated with a surgical site infection? (3) What are the common organisms isolated from an elbow infection after open treatment? One thousand three hundred twenty adult patients underwent surgery for an elbow fracture between January 2002 and July 2014 and were included in our study. Forty-eight of 1320 patients (4%) had a surgical site infection develop. Thirty-four of 1113 patients with a closed fracture (3%) had a surgical site infection develop. For all elbow fractures, use of plate and screw fixation (adjusted odds ratio [OR]= 2.2; 95% CI, 1.0-4.5; p = 0.041) and use of external fixation before surgery (adjusted OR = 4.7; 95% CI, 1.1-21; p = 0.035) were associated with higher infection rates. When subset analysis was performed for closed fractures, only smoking (adjusted OR = 2.2; 95% CI, 1.1-4.5; p = 0.023) was associated with higher infection rates. Staphylococcus aureus was the most common bacteria cultured (59%). The only modifiable risk factor for a surgical site infection after open reduction and internal fixation was cigarette smoking. Plate fixation and temporary external fixation are likely surrogates for more complex injuries, therefore no recommendations should be inferred from this association. Surgeons should counsel patients who smoke. Level IV, prognostic study. C1 [Claessen, Femke M. A. P.; Braun, Yvonne; van Leeuwen, Wouter F.; Ring, David] Massachusetts Gen Hosp, Hand Surg, Boston, MA 02114 USA. [Dyer, George S.] Brigham Womens Hosp, Upper Extrem Div, Dept Orthopaed Surg, Boston, MA USA. [van den Bekerom, Michel P. J.] Onze Lieve Vrouw Hosp, Shoulder & Elbow Unit, Amsterdam, Netherlands. [Ring, David] Harvard Univ, Sch Med, Orthopaed Surg, Boston, MA 02115 USA. [Ring, David] Massachusetts Gen Hosp, Orthopaed Surg, Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Surg, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@mgh.harvard.edu FU Skeletal Dynamics (Miami, FL, USA); Biomet (Warsaw, IN, USA); Acumed (Hillsboro, OR, USA) FX One of the authors certifies that he (DR), or a member of his or her immediate family, has or may receive payments or benefits, during the study period, an amount of USD 10,000-USD 100,000 from Skeletal Dynamics (Miami, FL, USA); an amount of less than USD 10,000 from Biomet (Warsaw, IN, USA); and an amount of less than USD 10,000 from Acumed (Hillsboro, OR, USA) outside the submitted work. NR 35 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2016 VL 474 IS 2 BP 562 EP 570 DI 10.1007/s11999-015-4523-3 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DA7YQ UT WOS:000368021900048 PM 26304043 ER PT J AU Garvey, KC Telo, GH Needleman, JS Forbes, P Finkelstein, JA Laffel, LM AF Garvey, Katharine C. Telo, Gabriela H. Needleman, Joseph S. Forbes, Peter Finkelstein, Jonathan A. Laffel, Lori M. TI Health Care Transition in Young Adults With Type 1 Diabetes: Perspectives of Adult Endocrinologists in the US SO DIABETES CARE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; EMERGING ADULTS; ADOLESCENTS; YOUTH; SERVICES; MELLITUS; GASTROENTEROLOGISTS; PREVALENCE; BARRIERS; SYSTEMS AB Objective Young adults with type 1 diabetes transitioning from pediatric to adult care are at risk for adverse outcomes. Our objective was to describe experiences, resources, and barriers reported by a national sample of adult endocrinologists receiving and caring for young adults with type 1 diabetes. RESEARCH DESIGN AND METHODS We fielded an electronic survey to adult endocrinologists with a valid e-mail address identified through the American Medical Association Physician Masterfile. RESULTS We received responses from 536 of 4,214 endocrinologists (response rate 13%); 418 surveys met the eligibility criteria. Respondents (57% male, 79% Caucasian) represented 47 states; 64% had been practicing > 10 years and 42% worked at an academic center. Only 36% of respondents reported often/always reviewing pediatric records and 11% reported receiving summaries for transitioning young adults with type 1 diabetes, although > 70% felt that these activities were important for patient care. While most respondents reported easy access to diabetes educators (94%) and dietitians (95%), fewer (42%) reported access to mental health professionals, especially in nonacademic settings. Controlling for practice setting and experience, endocrinologists without easy access to mental health professionals were more likely to report barriers to diabetes management for young adults with depression (odds ratio [OR] 5.3; 95% CI 3.4, 8.2), substance abuse (OR 3.5; 95% CI 2.2, 5.6), and eating disorders (OR 2.5; 95% CI 1.6, 3.8). CONCLUSIONS Our findings underscore the need for enhanced information transfer between pediatric and adult providers and increased mental health referral access for young adults with diabetes post-transition. C1 [Garvey, Katharine C.; Laffel, Lori M.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Telo, Gabriela H.; Needleman, Joseph S.; Laffel, Lori M.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Forbes, Peter] Boston Childrens Hosp, Clin Res Program, Boston, MA USA. [Finkelstein, Jonathan A.] Boston Childrens Hosp, Div Gen Pediat, Boston, MA USA. [Finkelstein, Jonathan A.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. RP Garvey, KC (reprint author), Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. EM katharine.garvey@childrens.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [K12DK094721, K23DK102655, P30DK036836]; National Institute of Child Health and Human Development [K24HD060786]; William Randolph Hearst Foundation; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]; Harvard University and its affiliated academic health care centers FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K12DK094721, K23DK102655, and P30DK036836), the National Institute of Child Health and Human Development (K24HD060786), and the William Randolph Hearst Foundation. This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic health care centers. NR 41 TC 2 Z9 2 U1 5 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2016 VL 39 IS 2 BP 190 EP 197 DI 10.2337/dc15-1775 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB4XF UT WOS:000368516200010 PM 26681724 ER PT J AU Munshi, MN Florez, H Huang, ES Kalyani, RR Mupanomunda, M Pandya, N Swift, CS Taveira, TH Haas, LB AF Munshi, Medha N. Florez, Hermes Huang, Elbert S. Kalyani, Rita R. Mupanomunda, Maria Pandya, Naushira Swift, Carrie S. Taveira, Tracey H. Haas, Linda B. TI Management of Diabetes in Longterm Care and Skilled Nursing Facilities: A Position Statement of the American Diabetes Association SO DIABETES CARE LA English DT Article ID HOME RESIDENTS; OLDER PATIENTS; GLYCEMIC CONTROL; PALLIATIVE CARE; HYPOGLYCEMIA; MELLITUS; PREVALENCE; PHYSICIANS; RISK; TRANSITIONS AB Diabetes is more common in older adults, has a high prevalence in long-term care (LTC) facilities, and is associated with significant disease burden and higher cost. The heterogeneity of this population with regard to comorbidities and overall health status is critical to establishing personalized goals and treatments for diabetes. The risk of hypoglycemia is the most important factor in determining glycemic goals due to the catastrophic consequences in this population. Simplified treatment regimens are preferred, and the sole use of sliding scale insulin (SSI) should be avoided. This position statement provides a classification system for older adults in LTC settings, describes how diabetes goals and management should be tailored based on comorbidities, delineates key issues to consider when using glucose-lowering agents in this population, and provides recommendations on how to replace SSI in LTC facilities. As these patients transition from one setting to another, or from one provider to another, their risk for adverse events increases. Strategies are presented to reduce these risks and ensure safe transitions. This article addresses diabetes management at end of life and in those receiving palliative and hospice care. The integration of diabetes management into LTC facilities is important and requires an interprofessional team approach. To facilitate this approach, acceptance by administrative personnel is needed, as are protocols and possibly system changes. It is important for clinicians to understand the characteristics, challenges, and barriers related to the older population living in LTC facilities as well as the proper functioning of the facilities themselves. Once these challenges are identified, individualized approaches can be designed to improve diabetes management while lowering the risk of hypoglycemia and ultimately improving quality of life. C1 [Munshi, Medha N.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Munshi, Medha N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Florez, Hermes] Miami Vet Affairs Healthcare Syst, Ctr Geriatr Res Educ & Clin, Miami, FL USA. [Florez, Hermes] Univ Miami, Miami, FL USA. [Huang, Elbert S.] Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. [Kalyani, Rita R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Mupanomunda, Maria] Amer Diabet Assoc, Alexandria, VA USA. [Pandya, Naushira] Nova SE Univ, Coll Osteopath Med, Dept Geriatr, Ft Lauderdale, FL 33314 USA. [Swift, Carrie S.] Kadlec Reg Med Ctr, Richland, WA USA. [Taveira, Tracey H.] Univ Rhode Isl, Coll Pharm, Providence, RI 02908 USA. RP Munshi, MN (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. EM mmunshi@bidmc.harvard.edu FU Midcareer Investigator Award in Patient-Oriented Research [K24 DK105340]; Chicago Center for Diabetes Translation Research [P30 DK092949]; National Institute of Diabetes and Digestive and Kidney Diseases [K23-DK093583]; Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) [UB4HP19211]; [R01 HS018542] FX E.S.H. is supported in part through the following grants: Midcareer Investigator Award in Patient-Oriented Research (K24 DK105340), the Chicago Center for Diabetes Translation Research (P30 DK092949), and a project grant (R01 HS018542). R.R.K. is supported in part by a grant fromthe National Institute of Diabetes and Digestive and Kidney Diseases (K23-DK093583). N.P. is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number UB4HP19211 "Geriatric Education Centers." NR 57 TC 9 Z9 9 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2016 VL 39 IS 2 BP 308 EP 318 DI 10.2337/dc15-2512 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB4XF UT WOS:000368516200025 PM 26798150 ER PT J AU Ganda, OP AF Ganda, Om P. TI Fasting Until Noon Triggers Increased Postprandial Hyperglycemia and Impaired Insulin Response After Lunch and Dinner in Individuals With Type 2 Diabetes: A Randomized Clinical Trial. Diabetes Care 2015;38:1820-1826 SO DIABETES CARE LA English DT Editorial Material ID GLUCOSE C1 [Ganda, Om P.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Ganda, OP (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM om.ganda@joslin.harvard.edu NR 7 TC 0 Z9 0 U1 3 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2016 VL 39 IS 2 BP E28 EP E28 DI 10.2337/dc15-2362 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB4XF UT WOS:000368516200007 PM 26798157 ER PT J AU Takx, RAP MacNabb, MH Emami, H Abdelbaky, A Singh, P Lavender, ZR di Carli, M Taqueti, V Foster, C Mann, J Comley, RA Weber, CIK Tawakol, A AF Takx, Richard A. P. MacNabb, Megan H. Emami, Hamed Abdelbaky, Amr Singh, Parmanand Lavender, Zachary R. di Carli, Marcelo Taqueti, Viviany Foster, Courtney Mann, Jessica Comley, Robert A. Weber, Chek Ing Kiu Tawakol, Ahmed TI Increased arterial inflammation in individuals with stage 3 chronic kidney disease SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE Atherosclerosis; Chronic kidney disease; FDGPET/CT; Inflammation ID POSITRON-EMISSION-TOMOGRAPHY; ATHEROSCLEROTIC PLAQUE INFLAMMATION; RENAL-DISEASE; VASCULAR CALCIFICATION; CARDIOVASCULAR EVENTS; FLUORODEOXYGLUCOSE; THERAPY; RISK; PET; QUANTIFICATION AB Purpose While it is well known that patients with chronic kidney disease (CKD) are at increased risk for the development and progression of atherosclerosis, it is not known whether arterial inflammation is increased in mild CKD. The aim of this study was to compare arterial inflammation using F-18-FDG PET/CT in patients with CKD and in matched controls. Methods This restrospective study included 128 patients undergoing FDG PET/CT imaging for clinical indications, comprising 64 patients with stage 3 CKD and 64 control patients matched by age, gender, and cancer history. CKD was defined according to guidelines using a calculated glomerular filtration rate (eGFR). Arterial inflammation was measured in the ascending aorta as FDG uptake on PET. Background FDG uptake (venous, subcutaneous fat and muscle) were recorded. Coronary artery calcification (CAC) was assessed using the CT images. The impact of CKD on arterial inflammation and CAC was then assessed. Results Arterial inflammation was higher in patients with CKD than in matched controls (standardized uptake value, SUV: 2.41 +/- 0.49 vs. 2.16 +/- 0.43; p=0.002). Arterial SUV correlated inversely with eGFR (r=-0.299, p=0.001). Venous SUV was also significantly elevated in patients with CKD, while subcutaneous fat and muscle tissue SUVs did not differ between groups. Moreover, arterial SUV remained significantly elevated in patients with CKD compared to controls after correcting for muscle and fat background, and also remained significant after adjusting for clinical risk factors. Further, CKD was associated with arterial inflammation (SUV) independent of the presence of subclinical atherosclerosis (CAC). Conclusion Moderate CKD is associated with increased arterial inflammation beyond that of controls. Further, the increased arterial inflammation is independent of presence of subclinical atherosclerosis. Current risk stratification tools may underestimate the presence of atherosclerosis in patients with CKD and thereby the risk of cardiovascular events. C1 [Takx, Richard A. P.; MacNabb, Megan H.; Emami, Hamed; Abdelbaky, Amr; Singh, Parmanand; Lavender, Zachary R.; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Takx, Richard A. P.; MacNabb, Megan H.; Emami, Hamed; Abdelbaky, Amr; Singh, Parmanand; Lavender, Zachary R.; di Carli, Marcelo; Taqueti, Viviany; Foster, Courtney; Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Takx, Richard A. P.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands. [di Carli, Marcelo; Taqueti, Viviany; Foster, Courtney] Brigham & Womens Hosp, Dept Med, Div Radiol, Boston, MA 02115 USA. [Mann, Jessica; Comley, Robert A.; Weber, Chek Ing Kiu] F Hoffmann La Roche Ltd, Basel, Switzerland. [Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singh, Parmanand] New York Presbyterian Hosp, Div Cardiol, Weill Cornell Med Coll, New York, NY USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. EM atawakol@partners.org FU F. Hoffmann-La Roche Ltd., Switzerland FX F. Hoffmann-La Roche Ltd., Switzerland NR 29 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 EI 1619-7089 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD FEB PY 2016 VL 43 IS 2 BP 333 EP 339 DI 10.1007/s00259-015-3203-6 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DA6MF UT WOS:000367918200017 ER PT J AU Digumarthy, SR Kovacina, B Otrakji, A Lanuti, M Shepard, JAO Sharma, A AF Digumarthy, Subba R. Kovacina, Bojan Otrakji, Alexi Lanuti, Michael Shepard, Jo-Anne O. Sharma, Amita TI Percutaneous CT guided lung biopsy in patients with pulmonary hypertension: Assessment of complications SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE CT; Biopsy; Pulmonary hypertension; Chest; Lung nodules ID TRANSTHORACIC NEEDLE-BIOPSY; OF-THE-LITERATURE; DOPPLER-ECHOCARDIOGRAPHY; VASCULAR-RESISTANCE; SYSTOLIC PRESSURE; ASPIRATION BIOPSY; PNEUMOTHORAX RATE; NODULES; GUIDELINES; HEMORRHAGE AB Purpose: To assess the complications of CT-guided percutaneous transthoracic needle aspiration and/or core biopsy (PTNAB) of lung nodules in patients with pulmonary arterial hypertension (PHTN). Method and materials: We analyzed PTNAB of 74 lung lesions (mean size: 3.6+/-2.1 cm) in 74 patients (M: F 38:36; age 68+/-15 years) with documented PHTN on cardiac ultrasound. 39 patients with lung lesions (M: F 24:15; age 65+/-14) who underwent PTNAB in the same period with right ventricle systolic pressure (RVSP) <35 mmHg were selected as controls. Pulmonary arterial pressures were estimated on cardiac ultrasounds by using the tricuspid regurgitation jet method. Two thoracic radiologists reviewed the medical records and PTNAB images on a PACS station and documented nodule size, location, distance traversed in lung, technical success and complications. Results: Fine needle aspirates were obtained in all and core biopsy in 23% (17174) of the nodules. 61% (45174) of the nodules were in the middle and 39% (29174) were in the outer third of lung. PHTN was mild, moderate and severe in 84% (62174), 13% (10174) and 3% (2174) of the patients. Biopsy was complicated by hemorrhage in 26% (19174), moderate hemoptysis in 1.3% (1174), pneumothorax in 17% (12174), chest tube in 1.3% (1174) and hemothorax in 1.3% (1174) of the patients. The complications rate in control group was similar, hemorrhage in 33% (19139) (p= 0.6), moderate hemoptysis in 5% (2139) (p= 0.3), pneumothorax in 28% (11139)(p= 0.2), chest tube in (0139)(p= 0.3), and hemothorax in 3% (1139) of the patients (p = 0.7). Conclusion: Percutaneous needle biopsy of lung lesions in patients with mild to moderate PHTN can be performed without significant increase in complications. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Digumarthy, Subba R.; Otrakji, Alexi; Shepard, Jo-Anne O.; Sharma, Amita] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Imaging,Dept Radiol, Boston, MA 02114 USA. [Lanuti, Michael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Kovacina, Bojan] McGill Univ, Montreal Gen Hosp, Dept Radiol, Montreal, PQ H3G 1A4, Canada. RP Digumarthy, SR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Imaging,Dept Radiol, 55 Fruit St,Founders 213, Boston, MA 02114 USA. EM sdigumarthy@mgh.harvard.edu NR 29 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD FEB PY 2016 VL 85 IS 2 BP 466 EP 471 DI 10.1016/j.ejrad.2015.12.007 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB1NW UT WOS:000368276000018 PM 26781153 ER PT J AU Pfarr, N Sinn, HP Klauschen, F Flechtenmacher, C Bockmayr, M Ridinger, K von Winterfeld, M Warth, A Lorenz, K Budczies, J Penzel, R Lennerz, JK Endris, V Weichert, W Stenzinger, A AF Pfarr, Nicole Sinn, Hans-Peter Klauschen, Frederick Flechtenmacher, Christa Bockmayr, Michael Ridinger, Kathrin von Winterfeld, Moritz Warth, Arne Lorenz, Katja Budczies, Jan Penzel, Roland Lennerz, Jochen K. Endris, Volker Weichert, Wilko Stenzinger, Albrecht TI Mutations in Genes Encoding PI3K-AKT and MAPK Signaling Define Anogenital Papillary Hidradenoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID MAMMARY-LIKE GLANDS; HUMAN-PAPILLOMAVIRUS; VULVA; PAPILLIFERUM; TUMORS; DISEASE; ADENOCARCINOMA; CARCINOMA; BIOLOGY; LESIONS AB Papillary hidradenoma (a.k.a. hidradenoma papilliferum) is a benign tumor of the anogenital region that almost exclusively arises in middle-aged Caucasian women. These tumors may recur and rare cases of malignant development have been reported. The genetic basis of papillary hidradenoma is currently unknown. Hence, we employed targeted high-coverage next generation sequencing interrogating 50 cancer-related genes and conventional Sanger sequencing to investigate the mutational landscape in a cohort of 15 cases. Additionally, we analyzed the HPV status of these tumors. Thirteen cases (87%) harbored mutations in cancer-related genes. Recurrent mutations in PIK3CA and AKT1 were present in 10 of the cases (67%). One PIK3CA mutated case had a concomitant STK11 mutation. Three cases harbored mutually exclusive mutations in BRAF, APC and ERBB4. The remaining two cases showed no mutations. None of the cases harbored DNA of human papilloma virus. Our results also provide evidence that -just as BRAF V600E mutations in hyperplastic polyps and benign nevi- a mutated driver gene does not imply malignant behavior per se but may set the basis for malignant transformation. The latter point may explain why rare cases of papillary hidradenoma have been reported to take a malignant course. Lastly, our genetic data may suggest treatment avenues beyond conventional surgery for some of these tumors. (C) 2015 Wiley Periodicals, Inc. C1 [Pfarr, Nicole; Weichert, Wilko] TUM, Inst Pathol, D-81675 Munich, Germany. [Sinn, Hans-Peter; Flechtenmacher, Christa; Ridinger, Kathrin; Warth, Arne; Lorenz, Katja; Penzel, Roland; Endris, Volker; Weichert, Wilko; Stenzinger, Albrecht] Univ Heidelberg Hosp, Inst Pathol, D-69120 Heidelberg, Germany. [Klauschen, Frederick; Bockmayr, Michael; von Winterfeld, Moritz; Budczies, Jan] Charite, Inst Pathol, D-10117 Berlin, Germany. [Lennerz, Jochen K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,CID, Boston, MA 02114 USA. [Weichert, Wilko; Stenzinger, Albrecht] Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Weichert, Wilko] German Canc Consortium DKTK, Heidelberg, Germany. [Stenzinger, Albrecht] Heidelberg Sch Oncol NCT HSO, Natl Ctr Tumor Dis, Heidelberg, Germany. RP Stenzinger, A (reprint author), Univ Heidelberg Hosp, Inst Pathol, Neuenheimer Feld 224, D-69120 Heidelberg, Germany. EM albrecht.stenzinger@med.uni-heidelberg.de FU National Center for Tumor Diseases (Heidelberg, Germany) FX The authors thank the staff of the tissue bank of the National Center for Tumor Diseases (Heidelberg, Germany) for their support and help with tissue handling. Further, they acknowledge excellent technical assistance of Angelika Bruntgens, Angelika Bonisch, and Waltraud Schmitz. NR 33 TC 4 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-2257 EI 1098-2264 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD FEB PY 2016 VL 55 IS 2 BP 113 EP 119 DI 10.1002/gcc.22315 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA DB1HR UT WOS:000368259600001 PM 26493284 ER PT J AU Lu, C Winkelman, M Wong, SS AF Lu, Catherine Winkelman, Megan Wong, Shane Shucheng TI Tablet-based education to reduce depression-related stigma SO HEALTH EDUCATION JOURNAL LA English DT Article DE Depression literacy; multimedia application; psychoeducation; stigma ID MENTAL-ILLNESS; HEALTH LITERACY; SELF-STIGMA; CARE AB Objectives: This study investigated the efficacy of a tablet-based multimedia education application, the Project Not Alone Depression Module, in improving depression literacy and reducing depression stigma among a community-based mental health clinic population. Methods: A total of 93 participants completed either a tablet-based multimedia education or a print education module containing the same content on depression. Primary outcomes were changes in depression literacy as measured by a knowledge quiz and stigma as measured by the Depression Stigma Scale administered before and after the education intervention. Secondary outcomes included participant preference, ease of use, and likeliness to discuss topic with a physician. Results: In comparison to print education, tablet-based multimedia education significantly increased depression-related knowledge and reduced depression stigma (p < .05). Among all participants, a reduction in the personal stigma score was correlated with an increase in knowledge score (p < .05). Participants preferred the tablet-based module to a human health educator (p < .05). Conclusion: With advantages of scalability, user preference, and efficacy in improving depression literacy and stigma, tablet-based multimedia education has the potential to improve the health outcomes of mental health clinic populations. Although the study findings are limited by small sample size and lack of randomisation, the results are encouraging for future research and development in tablet-based multimedia patient education. C1 [Lu, Catherine; Winkelman, Megan; Wong, Shane Shucheng] Stanford Univ, Stanford, CA 94305 USA. [Wong, Shane Shucheng] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Wong, SS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Parkman St,WACC 812, Boston, MA 02114 USA. EM swong20@partners.org FU Dalai Llama Fellows Program FX This research received funding support from the Dalai Llama Fellows Program. NR 17 TC 0 Z9 0 U1 3 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0017-8969 EI 1748-8176 J9 HEALTH EDUC J JI Health Educ. J. PD FEB PY 2016 VL 75 IS 1 BP 84 EP 93 DI 10.1177/0017896914568434 PG 10 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA DB1TF UT WOS:000368291200008 ER PT J AU Cajaiba, MM Khanna, G Smith, EA Gellert, L Chi, YY Mullen, EA Hill, DA Geller, JI Dome, JS Perlman, EJ AF Cajaiba, Mariana M. Khanna, Geetika Smith, Ethan A. Gellert, Lan Chi, Yueh-Yun Mullen, Elizabeth A. Hill, Dana A. Geller, James I. Dome, Jeffrey S. Perlman, Elizabeth J. TI Pediatric cystic nephromas: distinctive features and frequent DICER1 mutations SO HUMAN PATHOLOGY LA English DT Article DE Cystic nephromas; DICER1; Pediatric renal tumors; Renal development; Renal cystic lesions ID STROMAL TUMOR; PLEUROPULMONARY BLASTOMA; MULTILOCULAR CYST; KIDNEY AB Cystic nephromas (CNs) are uncommon benign renal neoplasms that present with a bimodal age distribution, affecting either infants/young children or adult females. Although differences between these age groups have been suggested, large studies of pediatric CN have not been conducted. As a result, the nomenclature and diagnostic criteria for these lesions remain controversial. In addition, the morphological overlap seen between CN and cystic partially differentiated nephroblastoma (CPDN) can result in diagnostic dilemmas. This study reviews the morphologic and radiographic features of 44 pediatric CN prospectively enrolled on a Children's Oncology Group protocol from 2007 to 2013. Although the typical multicystic architecture with thin septa described in adult CN was present in all of our pediatric cases, differences were also identified. We report distinctive features that add to the morphological spectrum of CN in children. Of the 44 cases, 16 had been previously analyzed and reported for DICER1 mutation, and either loss of function or missense mutations or both were identified in 15 of 16. In contrast, we analyzed 10 cases of adult CN, and all were negative for DICER/mutations; similarly, 6 CPDNs previously analyzed and reported were negative for DICER1 mutations. Therefore, the clinical, morphological, and genetic differences between pediatric and adult CN, as well as between CN and CPDN, suggest that these 3 lesions represent distinct entities. (C) 2015 Elsevier Inc. All rights reserved. C1 [Cajaiba, Mariana M.; Perlman, Elizabeth J.] Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pathol & Lab Med, Chicago, IL 60611 USA. [Cajaiba, Mariana M.; Perlman, Elizabeth J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Khanna, Geetika] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Smith, Ethan A.] Univ Michigan Hlth Syst, Dept Radiol, Ann Arbor, MI 48109 USA. [Gellert, Lan] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Chi, Yueh-Yun] Univ Florida, Dept Biostat, Gainesville, FL 32611 USA. [Mullen, Elizabeth A.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hill, Dana A.] Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. [Geller, James I.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Pediat Oncol, Cincinnati, OH 45229 USA. [Dome, Jeffrey S.] Childrens Natl Med Ctr, Div Pediat Oncol, Washington, DC 20010 USA. RP Cajaiba, MM (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, 225 East Chicago Ave,Room 08-413, Chicago, IL 60642 USA. EM mcajaiba@luriechildrens.org FU National Institutes of Health to the Children's Oncology Group [U10CA180886, U10CA180899, U10CA098543] FX This study was supported by grants from the National Institutes of Health to the Children's Oncology Group (U10CA180886, U10CA180899, and U10CA098543). NR 24 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 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2016 VL 48 BP 81 EP 87 DI 10.1016/j.humpath.2015.08.022 PG 7 WC Pathology SC Pathology GA DB2DT UT WOS:000368319200012 PM 26772403 ER PT J AU Gupta, RK Xie, BH Patton, KT Lisovsky, M Burks, E Behrman, SW Klimstra, D Deshpande, V AF Gupta, Rajib K. Xie, Bill H. Patton, Kurt T. Lisovsky, Mikhail Burks, Eric Behrman, Stephen W. Klimstra, David Deshpande, Vikram TI Follicular pancreatitis: a distinct form of chronic pancreatitis-an additional mimic of pancreatic neoplasms SO HUMAN PATHOLOGY LA English DT Article DE Follicular pancreatitis; Autoimmune pancreatitis; IgG4; Pancreatitis; Lymphoma ID LOCALIZED LYMPHOID HYPERPLASIA; AUTOIMMUNE PANCREATITIS; IGG4-RELATED DISEASE; PSEUDOLYMPHOMA; CANCER AB Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis Immunohistochemistry for Bcl-2, CD21, k and lambda light chains as well as IgG4 and IgG were performed. We found a total of 6 patients (male-female ratio, 2:1; mean age, 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis, while two presented with abdominal pain, fatigue, and elevated liver enzymes. On imaging, 3 patients had a discrete solid mass, whereas 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatin portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2-negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis, or granulocytic epithelial lesions. IgG4-to-IgG ratio was <40% in 5 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers. (C) 2015 Elsevier Inc. All rights reserved. C1 [Gupta, Rajib K.] Univ Tennessee, Hlth Sci Ctr, Dept Pathol & Lab Med, Memphis, TN 38163 USA. [Xie, Bill H.; Patton, Kurt T.] Trumbull Labs, Pathol Grp Midsouth, Germantown, TN 38138 USA. [Xie, Bill H.; Patton, Kurt T.] Baptist Mem Hosp, Dept Pathol, Memphis, TN 38120 USA. [Lisovsky, Mikhail] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. [Lisovsky, Mikhail] Geisel Sch Med Dartmouth, Lebanon, NH USA. [Burks, Eric] Lahey Hosp, Dept Pathol, Burlington, MA 01805 USA. [Behrman, Stephen W.] Univ Tennessee, Hlth Sci Ctr, Dept Surg, Div Surg Oncol, Memphis, TN 38163 USA. [Behrman, Stephen W.] Baptist Mem Hosp, Dept Surg, Memphis, TN 38120 USA. [Klimstra, David] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Klimstra, David] Mem Hosp Canc & Allied Dis, New York, NY 10065 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Deshpande, Vikram] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM rajibgupta2011@gmail.com; hbup@yahoo.com; kurt_patton@yahoo.com; mikhail.lisovslcy@hitchcock.org; eric.burks@lahey.org; sbehrman@uthsc.edu; klimstrd@mskcc.org FU NCI NIH HHS [P30 CA008748] NR 15 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2016 VL 48 BP 154 EP 162 DI 10.1016/j.humpath.2015.09.017 PG 9 WC Pathology SC Pathology GA DB2DT UT WOS:000368319200022 PM 26563969 ER PT J AU Seltman, HJ Mitchell, S Sweet, RA AF Seltman, Howard J. Mitchell, Shaina Sweet, Robert A. TI A Bayesian model of psychosis symptom trajectory in Alzheimer's disease SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Alzheimer's disease; cognitive impairment; neuropsychiatric symptoms ID LAST 2 DECADES; CARDIOVASCULAR HEALTH; COGNITIVE IMPAIRMENT; DIAGNOSIS AB ObjectivePsychosis, like other neuropsychiatric symptoms of dementia, has many features that make predictive modeling of its onset difficult. For example, psychosis onset is associated with both the absolute degree of cognitive impairment and the rate of cognitive decline. Moreover, psychotic symptoms, while more likely than not to persist over time within individuals, may remit and recur. To facilitate predictive modeling of psychosis for personalized clinical decision making, including evaluating the role of risk genes in its onset, we have developed a novel Bayesian model of the dual trajectories of cognition and psychosis symptoms. MethodsCognition was modeled as a four-parameter logistic curve with random effects for all four parameters and possible covariates for the rate and time of fall. Psychosis was modeled as a continuous-time hidden Markov model with a latent never-psychotic class and states for pre-psychotic, actively psychotic and remitted psychosis. Covariates can affect the probability of being in the never-psychotic class. Covariates and the level of cognition can affect the transition rates for the hidden Markov model. ResultsThe model characteristics were confirmed using simulated data. Results from 434 AD patients show that a decline in cognition is associated with an increased rate of transition to the psychotic state. ConclusionsThe model allows declining cognition as an input for psychosis prediction, while incorporating the full uncertainty of the interpolated cognition values. The techniques used can be used in future genetic studies of AD and are generalizable to the study of other neuropsychiatric symptoms in dementia. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Seltman, Howard J.] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Mitchell, Shaina] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. RP Seltman, HJ (reprint author), Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. EM hseltman@stat.cmu.edu FU National Institutes of Health [AG 027224] FX This work was supported in part by the National Institutes of Health grant AG 027224. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, the Department of Veterans Affairs, or the United States Government. NR 19 TC 1 Z9 1 U1 4 U2 10 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 FEB PY 2016 VL 31 IS 2 BP 204 EP 210 DI 10.1002/gps.4326 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA DA8BU UT WOS:000368030100013 PM 26216660 ER PT J AU Inverso, G Chuang, SK Kaban, LB AF Inverso, Gino Chuang, Sung-Kiang Kaban, Leonard B. TI Oral and Maxillofacial Surgery Foundation Research and Fellowship Awards: A 26-Year Review at Massachusetts General Hospital and Harvard School of Dental Medicine SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID CAREER AB Purpose: The purpose of this study was to review outcomes of the Oral and Maxillofacial Surgery (OMS) Foundation's funding awards to members of the OMS department at Massachusetts General Hospital (MGH) in terms of projects completed, abstracts presented, peer-reviewed publications, and career trajectories of recipients. Materials and Methods: Datawere collected from MGH and OMS Foundation records and interviews with award recipients. Primary outcome variables included 1) number of awards and award types, 2) funding amount, 3) project completion, 4) number of presented abstracts, 5) conversion from abstracts to publications, 6) number of peer-reviewed publications, 7) career trajectories of awardees, and 8) additional extramural funding. Results: Eleven Student Research Training Awards provided $135,000 for 39 projects conducted by 37 students. Of these, 34 (87.2%) were completed. There were 30 student abstracts presented, 21 peer-reviewed publications, and a publication conversion rate of 58.8%. Faculty research awards comprised $1,510,970 for 22 research projects by 12 faculty members and two research fellows. Of the 22 funded projects, 21 (95.5%) were completed. There were 110 faculty and research fellow abstracts presented and 113 peer-reviewed publications, for a publication conversion rate of 93.8%. In the student group, 17 of 37 (45.9%) are enrolled in or are applying for OMS residencies. Of the 10 students who have completed OMS training, 3 (30%) are in full-time academic positions. Of the 12 faculty recipients, 9 (75%) remain in OMS academic practice. During this time period, the department received $9.9 million of extramural foundation or National Institutes of Health funding directly or indirectly related to the OMS Foundation grants. Conclusions: The results of this study indicate that 90.2% of projects funded by the OMS Foundation have been completed. Most projects resulted in abstracts and publications in peer-reviewed journals. These grants encouraged students to pursue OMS careers and aided OMS faculty in developing their research programs. (C) 2016 American Association of Oral and Maxillofacial Surgeons C1 [Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Inverso, Gino] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. EM Kaban.Leonard@mgh.harvard.edu FU Department of Oral and Maxillofacial Surgery Education and Research Fund; Harvard Medical School Enrichment Fund FX This project was supported by the Department of Oral and Maxillofacial Surgery Education and Research Fund and the Harvard Medical School Enrichment Fund. NR 6 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2016 VL 74 IS 2 BP 234 EP 238 DI 10.1016/j.joms.2015.08.012 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DB1KG UT WOS:000368266500005 PM 26343762 ER PT J AU McClave, SA Taylor, BE Martindale, RG Warren, MM Johnson, DR Braunschweig, C McCarthy, MS Davanos, E Rice, TW Cresci, GA Gervasio, JM Sacks, GS Roberts, PR Compher, C AF McClave, Stephen A. Taylor, Beth E. Martindale, Robert G. Warren, Malissa M. Johnson, Debbie R. Braunschweig, Carol McCarthy, Mary S. Davanos, Evangelia Rice, Todd W. Cresci, Gail A. Gervasio, Jane M. Sacks, Gordon S. Roberts, Pamela R. Compher, Charlene CA Soc Critical Care Med Amer Soc Parenteral Enteral Nutr TI Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN) SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article DE nutrition; critical care; intensive care unit; enteral; parenteral; evidence-based medicine; Grading of Recommendations, Assessment, Development, and Evaluation criteria; guidelines ID RANDOMIZED CONTROLLED-TRIAL; SEVERE ACUTE-PANCREATITIS; RESTING ENERGY-EXPENDITURE; MECHANICALLY VENTILATED PATIENTS; GAMMA-LINOLENIC ACID; INFLAMMATORY RESPONSE SYNDROME; INTENSIVE INSULIN THERAPY; PLACEBO-CONTROLLED TRIAL; MILD ACUTE-PANCREATITIS; TRAUMATIC BRAIN-INJURY C1 [McClave, Stephen A.] Univ Louisville, Dept Med, Louisville, KY 40292 USA. [Taylor, Beth E.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Martindale, Robert G.] Oregon Hlth & Sci Univ, Div Gen Surg, Portland, OR 97201 USA. [Warren, Malissa M.] Portland VA Med Ctr, Portland, OR USA. [Johnson, Debbie R.] Univ Wisconsin Hosp & Clin, UW Hlth, Wound Skin Ost, Madison, WI 53792 USA. [Braunschweig, Carol] Univ Illinois, Dept Kinesiol & Nutr, Chicago, IL USA. [Braunschweig, Carol] Univ Illinois, Div Epidemiol & Biostat, Chicago, IL USA. [McCarthy, Mary S.] Madigan Healthcare Syst, Ctr Nursing Sci & Clin Inquiry, Tacoma, WA USA. [Davanos, Evangelia] Brooklyn Hosp Ctr, Nutr Support, Brooklyn, NY USA. [Rice, Todd W.] Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Med, Nashville, TN 37235 USA. [Cresci, Gail A.] Inst Digest Dis, Gastroenterol & Pathobiol, Cleveland, OH USA. [Gervasio, Jane M.] Butler Univ, Coll Pharm & Hlth Sci, Indianapolis, IN 46208 USA. [Sacks, Gordon S.] Auburn Univ, Harrison Sch Pharm, Dept Pharm Practice, Auburn, AL 36849 USA. [Roberts, Pamela R.] Res John A Moffitt Endowed Chair, Dept Anesthesiol, Div Chief Crit Care Med, Oklahoma City, OK USA. [Compher, Charlene] Univ Penn, Sch Nursing, Nutr Sci, Philadelphia, PA 19104 USA. RP Compher, C (reprint author), Univ Penn, Sch Nursing, Nutr Sci, Philadelphia, PA 19104 USA. EM stephen.mcclave@louisville.edu; compherc@nursing.upenn.edu FU Metagenics; Fresenius Kabi USA, LLC; March of Dimes Foundation FX Dr Taylor disclosed serving as an A.S.P.E.N. committee member and Dietitians in Nutrition Support past chair. Dr McClave disclosed other relationships with Nestle (consulting), Abbott (speaker), Metagenics (consulting), Covidien (consultant), and A.S.P.E.N. Dr Martindale disclosed other relationships with Davol, LifeCell, and Metagenics (consultant) and received funding from Metagenics (research grant recipient). Dr Warren disclosed serving as cochair for the Veterans Health Administration Dietary Supplement Committee and as a chair for the Dietitians in Nutrition Support Webinar Planning Committee. Dr Johnson disclosed that she does not have any potential conflicts of interest. Dr Braunschweig disclosed serving as the A.S.P.E.N. editor for clinical guidelines. Dr McCarthy disclosed serving as an A.S.P.E.N. committee member for the Research Committee and the Abstract Review Committee, an A.S.P.E.N. Nursing Section member, and a SCCM Nursing Section member. Dr Davanos disclosed other relationships with Baxter Healthcare (medical science liaison and employee) and NY/LISPEN chapter (president-elect). Dr Rice disclosed other relationships with Avisa, LLC (consultant) and GSK (Data and Safety Monitoring Board) and served as an expert witness. Dr Cresci disclosed other relationships with Metagenics, Advocare, and Covidien; received funding from Metagenics (research grant, speaker); and served as a Research Committee member for A.S.P.E.N. and Dietitians in Nutrition Support (chair of the Symposium Planning Committee). Dr Gervasio disclosed serving as an A.S.P.E.N. committee member. Dr Sacks disclosed other relationships with Fresenius Kabi USA, LLC (research grant recipient) and A.S.P.E.N. (president and member of Board of Directors, A.S.P.E.N. Rhoads Research Foundation-Board of Advisors). Dr Roberts disclosed other relationships as an American Society of Anesthesiologists committee member (critical care) and as an A.S.P.E.N. committee member (abstract reviews). Dr Compher received funding from the March of Dimes Foundation (research grant recipient) and disclosed other relationships with A.S.P.E.N. (Board of Directors and president-elect). NR 481 TC 63 Z9 81 U1 19 U2 39 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 EI 1941-2444 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD FEB PY 2016 VL 40 IS 2 BP 159 EP 211 DI 10.1177/0148607115621863 PG 53 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DB1TS UT WOS:000368292500002 PM 26773077 ER PT J AU Bergamaschi, CC Santamaria, MP Berto, LA Cogo-Muller, K Motta, RHL Salum, EA Nociti, FH Goodson, JM Groppo, FC AF Bergamaschi, C. C. Santamaria, M. P. Berto, L. A. Cogo-Mueller, K. Motta, R. H. L. Salum, E. A. Nociti Junior, F. H. Goodson, J. M. Groppo, F. C. TI Full mouth periodontal debridement with or without adjunctive metronidazole gel in smoking patients with chronic periodontitis: A pilot study SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE adjunctive periodontal therapy; metronidazole; periodontitis; smoking ID PROFESSIONAL PLAQUE REMOVAL; ULTRASONIC DEBRIDEMENT; SYSTEMIC METRONIDAZOLE; CIGARETTE-SMOKING; AGGRESSIVE PERIODONTITIS; SUBGINGIVAL MICROFLORA; BRAZILIAN POPULATION; THERAPY; SMOKERS; AMOXICILLIN AB Background and ObjectiveThe evidence of effectiveness of metronidazole (Mtz) as an adjunct therapy to periodontal procedure in the treatment of patients with chronic periodontitis is not conclusive. The aim of this study was to compare the effect of Mtz (delivered locally as a gel or systemically as a tablet) as an adjunctive therapy with full mouth periodontal debridement (1h of ultrasonic calculus/plaque removal) in smokers with chronic periodontitis. Material and MethodsThis pilot study involved 30 smokers with at least six teeth with a clinical attachment loss of 5mm and probing pocket depth (PPD) of 5mm. They were randomly assigned into one of three groups (n=10): (i) 3g daily of placebo gel applied topically (using a dental tray with the gel overnight) + periodontal debridement; (ii) 3g daily of a 15% Mtz benzoate gel applied topically (using a dental tray with the gel overnight) + periodontal debridement; and (iii) a daily single dose of 750mg Mtz (Flagyl((R))) + periodontal debridement. Clinical parameters (visible plaque index, gingival bleeding index [GBI], relative attachment level and PPD) and quantitative analysis (by real-time polymerase chain reaction) of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia were assessed at baseline and at 1, 3 and 6mo after periodontal debridement. ResultsThere was no statistically significant difference in the average GBI and visible plaque index values at baseline between the groups (p0.05). There was no significant difference between groups in all parameters evaluated (p0.05). Significant reductions in GBI at 3 and 6mo were observed in all groups (p<0.05). Significant reductions in both PPD and relative attachment level at 1, 3 and 6mo were observed in all groups (p<0.05). Significant reductions in bacterial levels at 7 and 30d were observed in all groups (p<0.05). ConclusionAdjunctive use of Mtz (gel or tablet) to periodontal debridement had similar clinical and microbiological improvement compared to treatment with placebo + periodontal debridement in smokers with chronic periodontitis up to 6mo post-treatment. Further studies are necessary to confirm the clinical relevance of these findings. C1 [Bergamaschi, C. C.] Univ Sorocaba, Dept Pharmaceut Sci, BR-18023000 Sorocaba, SP, Brazil. [Santamaria, M. P.] State Univ Sao Paulo, Coll Dent, Div Periodont, Sao Jose Dos Campos, Brazil. [Berto, L. A.; Groppo, F. C.] Univ Estadual Campinas, Dent Sch Piracicaba, Dept Pharmacol Anesthesiol & Therapeut, Piracicaba, Brazil. [Cogo-Mueller, K.] Univ Santo Amaro, Dept Dent, Sao Paulo, Brazil. [Motta, R. H. L.] Sao Leopoldo Mandic Dent Sch, Dept Pharmacol Anesthesiol & Therapeut, Campinas, SP, Brazil. [Salum, E. A.; Nociti Junior, F. H.] Univ Estadual Campinas, Dent Sch Piracicaba, Dept Prosthodont & Periodontol, Piracicaba, Brazil. [Goodson, J. M.] Forsyth Inst, Dept Clin Res, Boston, MA USA. RP Bergamaschi, CC (reprint author), Univ Sorocaba, Rodovia Raposo Tavares Km 92-5, BR-18023000 Sorocaba, SP, Brazil. EM cristiane.motta@prof.uniso.br RI Berto, Luciana/L-1488-2014; santamaria, mauro/P-1263-2014; Cogo-Muller, Karina /H-2365-2012 OI Cogo-Muller, Karina /0000-0002-9048-8702 FU FAPESP [06/01492-0, 06/0898-9] FX The authors thank FAPESP for the scholarship and financial support for this research (FAPESP # 06/01492-0 and 06/0898-9) and Prof. Jorge Valerio for assistance in manuscript. NR 48 TC 1 Z9 1 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3484 EI 1600-0765 J9 J PERIODONTAL RES JI J. Periodont. Res. PD FEB PY 2016 VL 51 IS 1 BP 50 EP 59 DI 10.1111/jre.12278 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DA6XG UT WOS:000367948400005 PM 25900347 ER PT J AU Janssen, SJ van Dijke, M Lozano-Calderon, SA Ready, JE Raskin, KA Ferrone, ML Hornicek, FJ Schwab, JH AF Janssen, Stein J. van Dijke, Maarten Lozano-Calderon, Santiago A. Ready, John E. Raskin, Kevin A. Ferrone, Marco L. Hornicek, Francis J. Schwab, Joseph H. TI Complications after surgery for metastatic humeral lesions SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Humerus; operative; surgery metastases; carcinoma; myeloma; lymphoma ID RENAL-CELL CARCINOMA; OPERATIVE TREATMENT; SURVIVAL; FRACTURES; PROGNOSTICATION; DISEASE AB Background: Knowledge of surgical outcome and its predictors helps inform patients and aids in surgical decision-making. We aimed to assess the outcome-reoperation and systemic complication rate-of surgery for humeral metastases, myeloma, or lymphoma. Our null hypothesis was that there are no factors associated with these outcomes. Methods: We included 295 consecutive patients in this retrospective study: 134 (45%) proximal, 131 (44%) diaphyseal, and 30 (10%) distal impending or pathologic fractures. Proximal lesions were treated by intramedullary nailing (43%, n = 57), prosthesis (34%, n = 46), plate-screw fixation (22%, n = 30), and a combination (n = 1). Diaphyseal lesions were treated by intramedullary nailing (69%, n = 91), plate-screw fixation (30%, n = 39), and a combination (n = 1). Distal lesions were treated by platescrew fixation (97%, n = 29) and intramedullary nailing (3.3%, n = 1). Results: We found 25 (8.5%) reoperations, and 17 (5.8%) patients had 18 systemic complications: pneumonia (3.7%, n = 11), pulmonary embolism(1.3%, n = 4), sepsis (0.68%, n = 2), and fat embolism(0.34%, n = 1). No factors were independently associated with reoperation. Logistic regression analysis demonstrated that favorable cancer status (i.e., a higher modified Bauer score: odds ratio, 0.48; 95% confidence interval, 0.29-0.80; P =.005) was independently associated with a decreased systemic complication rate. Conclusion: Poor cancer status was an independent predictor of postoperative systemic complications. This could help inform the patient and anticipate postoperative problems. (C) 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Janssen, Stein J.; van Dijke, Maarten; Lozano-Calderon, Santiago A.; Raskin, Kevin A.; Hornicek, Francis J.; Schwab, Joseph H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Orthopaed Oncol Serv, Boston, MA USA. [Ready, John E.; Ferrone, Marco L.] Brigham & Womens Hosp, Orthopaed Oncol Serv, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Janssen, SJ (reprint author), Massachusetts Gen Hosp, Room 3-946,Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA. EM steinjanssen@gmail.com FU Anna Foundation; Michael van Vloten Foundation; De Drie Lichten Foundation; KWF Kankerbestrijding FX Stein J. Janssen has received research funding from Anna Foundation, Michael van Vloten Foundation, De Drie Lichten Foundation, and KWF Kankerbestrijding. NR 24 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 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD FEB PY 2016 VL 25 IS 2 BP 207 EP 215 DI 10.1016/j.jse.2015.08.009 PG 9 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA DB0YL UT WOS:000368234400010 PM 26547526 ER PT J AU ter Meulen, DP Janssen, SJ Hageman, MGJS Ring, DC AF ter Meulen, Dirk P. Janssen, Stein J. Hageman, Michiel G. J. S. Ring, David C. TI Quantitative three-dimensional computed tomography analysis of glenoid fracture patterns according to the AO/OTA classification SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Glenoid; fracture; three-dimensional; quantitative; surface area; classification ID SCAPULAR FRACTURES; CORONOID FRACTURES AB Hypothesis/Background: This study measures the characteristics of glenoid fractures to determine if the AO Foundation and Orthopaedic Trauma Association (AO/OTA) classification captures the most common fracture patterns. The primary null hypothesis was that surface area and degree of fragmentation do not differ among the different fracture types. Secondarily, we tested if there was a relationship between high- vs. low-energy trauma and fracture classification. Methods: Three-dimensional models were created for a consecutive series of 53 fractures. The fracture classifications, the number of fragments, and the fragmented articular surface area were related to the type of injury. The difference of articular surface size and number of fragments among classification groups was analyzed with the Kruskal-Wallis test. Results: There is a significant difference in fractured articular surface area among classification groups. Compared with transverse and multifragmented fractures, both anterior and posterior fractures involved significantly less of the articular surface area. High-energy trauma is associated with transverse and multifragmented fractures in 93% of the cases. It is associated with a greater number of fracture fragments and fracture of a larger percentage of the glenoid surface area, with a mean fractured surface of 60% for high-energy fractures and 25% for low-energy injuries. Discussion/Conclusion: Quantitative 3-dimensional CT analysis confirms that the current AO/OTA classification adequately characterizes and discriminates glenoid fracture patterns. The classification groups are related to the fragmented articular surface area and the number of fragments. Also, the mechanism of injury is related to the classification group, which supports the clinical relevance of the classification. (C) 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [ter Meulen, Dirk P.; Janssen, Stein J.; Hageman, Michiel G. J. S.; Ring, David C.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, DC (reprint author), Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 FU Skeletal Dynamics; Biomet FX David C. Ring has received study-specific grants from Skeletal Dynamics and Biomet. He is a consultant for Wright Medical, Skeletal Dynamics, and Acumed. He receives honoraria from AO North America and AO International. He receives royalties from Wright Medical, Biomet, and Skeletal Dynamics. He has stock options in Illuminos. NR 14 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 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD FEB PY 2016 VL 25 IS 2 BP 269 EP 275 DI 10.1016/j.jse.2015.07.022 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA DB0YL UT WOS:000368234400018 PM 26456425 ER PT J AU Wofford, J Fenves, AZ Jackson, JM Kimball, AB Menter, A AF Wofford, Jay Fenves, Andrew Z. Jackson, J. Mark Kimball, Alexa B. Menter, Alan TI Genetic causes of nephrocutaneous disease SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE autoimmune; dermatology; genetic; genodermatoses; inflammatory; nephrocutaneous; nephrology ID BECKWITH-WIEDEMANN-SYNDROME; TUBEROUS SCLEROSIS COMPLEX; NAIL-PATELLA SYNDROME; HIPPEL-LINDAU-DISEASE; HOGG-DUBE-SYNDROME; POLYCYSTIC KIDNEY-DISEASE; RENAL-CELL CANCER; FABRY-DISEASE; DIAGNOSTIC-CRITERIA; NEUROFIBROMATOSIS TYPE-1 AB There are a significant number of diseases and treatment considerations of considerable importance relating to the skin and renal systems. This emphasizes the need for dermatologists in practice or in clinical training to be aware of these associations. Part I of this 2-part continuing medical education article reviews the genetic syndromes with both renal and cutaneous involvement that are most important for the dermatologist to be able to identify, manage, and appropriately refer to nephrology colleagues. Part II reviews the inflammatory syndromes with relevant renal manifestations and therapeutic agents commonly used by dermatologists that have drug-induced effects on or require close consideration of renal function. In addition, we will likewise review therapeutic agents commonly used by nephrologists that have drug-induced effects on the skin that dermatologists are likely to encounter in clinical practice. In both parts of this continuing medical education article, we discuss diagnosis, management, and appropriate referral to our nephrology colleagues in the context of each nephrocutaneous association. There are a significant number of dermatoses associated with renal abnormalities and disease, emphasizing the need for dermatologists to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations with recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae. C1 [Wofford, Jay; Menter, Alan] Baylor Univ, Med Ctr, Dept Dermatol, Dallas, TX USA. [Fenves, Andrew Z.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Jackson, J. Mark] Univ Louisville, Dept Dermatol, Louisville, KY 40292 USA. RP Menter, A (reprint author), Texas Dermatol Associates, 3900 Junius St,Ste 145, Dallas, TX 75246 USA. EM amderm@gmail.com NR 83 TC 2 Z9 2 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2016 VL 74 IS 2 BP 231 EP 244 DI 10.1016/j.jaad.2015.05.039 PG 14 WC Dermatology SC Dermatology GA DB1MP UT WOS:000368272600009 PM 26775773 ER PT J AU Pascoe, VL Fenves, AZ Wofford, J Jackson, JM Menter, A Kimball, AB AF Pascoe, Vanessa L. Fenves, Andrew Z. Wofford, Jay Jackson, J. Mark Menter, Alan Kimball, Alexandra Boer TI Inflammatory and medication-related nephrocutaneous associations SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE antihypertensive medication; autoimmune; dermatology; genetic; genodermatoses; immunosuppression; inflammatory; medication side effects; nephrocutaneous; nephrology; renal transplantation ID CUTANEOUS LUPUS-ERYTHEMATOSUS; CALCIUM-CHANNEL BLOCKERS; ORGAN TRANSPLANT RECIPIENTS; STEVENS-JOHNSON SYNDROME; LOW-DOSE METHOTREXATE; TOXIC EPIDERMAL NECROLYSIS; HENOCH-SCHONLEIN PURPURA; OF-THE-LITERATURE; CONVERTING ENZYME-INHIBITORS; HYDRALAZINE-INDUCED LUPUS AB There are a significant number of dermatoses associated with renal abnormalities and disease, and dermatologists need to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations and recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae. Part II of this 2-part continuing medical education article addresses inflammatory and medication-related nephrocutaneous associations. C1 [Pascoe, Vanessa L.; Fenves, Andrew Z.; Kimball, Alexandra Boer] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Pascoe, Vanessa L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Wofford, Jay; Menter, Alan] Baylor Univ, Med Ctr, Dallas, TX USA. [Jackson, J. Mark] Univ Louisville, Div Dermatol, Louisville, KY 40292 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials & Outcomes Skin, 50 Staniford St,Ste 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 401 TC 1 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2016 VL 74 IS 2 BP 247 EP 270 DI 10.1016/j.jaad.2015.05.042 PG 24 WC Dermatology SC Dermatology GA DB1MP UT WOS:000368272600010 PM 26775774 ER PT J AU Sonpavde, G Pond, GR Rosenberg, JE Bajorin, DF Choueiri, TK Necchi, A Di Lorenzo, G Bellmunt, J AF Sonpavde, Guru Pond, Gregory R. Rosenberg, Jonathan E. Bajorin, Dean F. Choueiri, Toni K. Necchi, Andrea Di Lorenzo, Giuseppe Bellmunt, Joaquim TI Improved 5-Factor Prognostic Classification of Patients Receiving Salvage Systemic Therapy for Advanced Urothelial Carcinoma SO JOURNAL OF UROLOGY LA English DT Article DE urinary tract; urothelium; carcinoma; albumins; prognosis ID CISPLATIN-BASED CHEMOTHERAPY; TRANSITIONAL-CELL CARCINOMA; BLADDER-CANCER PATIENTS; PHASE-II; TRIAL DESIGN; PREDICTING SURVIVAL; SOLID TUMORS; SINGLE GROUP; SCORE GPS; PACLITAXEL AB Purpose: Prognostic factors in patients receiving salvage systemic therapy for advanced urothelial carcinoma include performance status, liver metastasis, hemoglobin and time since chemotherapy. We investigated the impact of albumin, and neutrophil, lymphocyte and platelet counts. Materials and Methods: Patient level data from 10 phase II trials were used. Cox proportional hazards regression was applied to evaluate associations with overall survival. An optimal regression model was constructed using forward stepwise selection and risk groups were defined using the number of adverse factors. Trial was a stratification factor. External validation was done in a separate data set of 5 salvage phase II trials. Results: Discovery data were obtained on 708 patients. After adjustment for the 4 known factors a platelet count of the upper limit of normal or greater and albumin less than the lower limit of normal were significant poor prognostic factors. Only the addition of albumin was externally validated. For 0 or 1, 2 and 3 or greater risk factors median overall survival was 8.9, 6.4 and 4.5 months in 207, 171 and 113 patients in the discovery data set of 491, and 10.6, 10.0 and 7.0 months in 73, 47 and 47 patients, respectively, in the validation data set of 167. By adding albumin the c-index improved from 0.610 to 0.639 in the discovery set and from 0.616 to 0.646 in the validation set. Conclusions: Albumin was externally validated as a prognostic factor for overall survival after accounting for time from prior chemotherapy, hemoglobin, performance status and liver metastasis status in patients receiving salvage systemic therapy for advanced urothelial carcinoma. The discovery of molecular prognostic factors is a priority to further enhance this new preferred 5-factor clinical prognostic model. C1 [Sonpavde, Guru] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Pond, Gregory R.] McMaster Univ, Hamilton, ON, Canada. [Rosenberg, Jonathan E.; Bajorin, Dean F.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Choueiri, Toni K.; Bellmunt, Joaquim] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, Toni K.; Bellmunt, Joaquim] Harvard Univ, Sch Med, Boston, MA USA. [Necchi, Andrea] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Di Lorenzo, Giuseppe] Univ Naples Federico II, Naples, Italy. RP Sonpavde, G (reprint author), Univ Alabama Birmingham, Ctr Comprehens Canc, 1720 2nd Ave South,NP2540B, Birmingham, AL 35294 USA. EM gsonpavde@uabmc.edu OI Rosenberg, Jonathan/0000-0003-2637-4249; Necchi, Andrea/0000-0002-3007-2756 FU NCI NIH HHS [P30 CA008748] NR 30 TC 10 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD FEB PY 2016 VL 195 IS 2 BP 277 EP 282 DI 10.1016/j.juro.2015.07.111 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DA8KZ UT WOS:000368054800011 PM 26292040 ER PT J AU Newcomb, LF Thompson, IM Boyer, HD Brooks, JD Carroll, PR Cooperberg, MR Dash, A Ellis, WJ Fazli, L Feng, ZD Gleave, ME Kunju, P Lance, RS McKenney, JK Meng, MV Nicolas, MM Sanda, MG Simko, J So, A Tretiakova, MS Troyer, DA True, LD Vakar-Lopez, F Virgin, J Wagner, AA Wei, JT Zheng, YY Nelson, PS Lin, DW AF Newcomb, Lisa F. Thompson, Ian M., Jr. Boyer, Hilary D. Brooks, James D. Carroll, Peter R. Cooperberg, Matthew R. Dash, Atreya Ellis, William J. Fazli, Ladan Feng, Ziding Gleave, Martin E. Kunju, Priya Lance, Raymond S. McKenney, Jesse K. Meng, Maxwell V. Nicolas, Marlo M. Sanda, Martin G. Simko, Jeffry So, Alan Tretiakova, Maria S. Troyer, Dean A. True, Lawrence D. Vakar-Lopez, Funda Virgin, Jeff Wagner, Andrew A. Wei, John T. Zheng, Yingye Nelson, Peter S. Lin, Daniel W. CA Canary PASS Investigators TI Outcomes of Active Surveillance for Clinically Localized Prostate Cancer in the Prospective, Multi-Institutional Canary PASS Cohort SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prospective studies; watchful waiting ID RADICAL PROSTATECTOMY; RISK-ASSESSMENT; DISEASE RECURRENCE; PREDICTION; ANTIGEN; TRENDS; VALIDATION; MANAGEMENT; PATHOLOGY; MEN AB Purpose: Active surveillance represents a strategy to address the overtreatment of prostate cancer, yet uncertainty regarding individual patient outcomes remains a concern. We evaluated outcomes in a prospective multicenter study of active surveillance. Materials and Methods: We studied 905 men in the prospective Canary PASS enrolled between 2008 and 2013. We collected clinical data at study entry and at prespecified intervals, and determined associations with adverse reclassification, defined as increased Gleason grade or greater cancer volume on followup biopsy. We also evaluated the relationships of clinical parameters with pathology findings in participants who underwent surgery after a period of active surveillance. Results: At a median followup of 28 months 24% of participants experienced adverse reclassification, of whom 53% underwent treatment while 31% continued on active surveillance. Overall 19% of participants received treatment, 68% with adverse reclassification, while 32% opted for treatment without disease reclassification. In multivariate Cox proportional hazards modeling the percent of biopsy cores with cancer, body mass index and prostate specific antigen density were associated with adverse reclassification (p = 0.01, 0.04, 0.04, respectively). Of 103 participants subsequently treated with radical prostatectomy 34% had adverse pathology, defined as primary pattern 4-5 or nonorgan confined disease, including 2 with positive lymph nodes, with no significant relationship between risk category at diagnosis and findings at surgery (p = 0.76). Conclusions: Most men remain on active surveillance at 5 years without adverse reclassification or adverse pathology at surgery. However, clinical factors had only a modest association with disease reclassification, supporting the need for approaches that improve the prediction of this outcome. C1 [Newcomb, Lisa F.; Boyer, Hilary D.; Feng, Ziding; Zheng, Yingye; Nelson, Peter S.; Lin, Daniel W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Newcomb, Lisa F.; Ellis, William J.; Tretiakova, Maria S.; True, Lawrence D.; Vakar-Lopez, Funda; Lin, Daniel W.] Univ Washington, Seattle, WA 98195 USA. [Dash, Atreya; Virgin, Jeff; Lin, Daniel W.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Brooks, James D.] Stanford Univ, Stanford, CA 94305 USA. [Carroll, Peter R.; Cooperberg, Matthew R.; Meng, Maxwell V.; Simko, Jeffry] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fazli, Ladan; Gleave, Martin E.; So, Alan] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Thompson, Ian M., Jr.; Nicolas, Marlo M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sanda, Martin G.; Wagner, Andrew A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Lance, Raymond S.; Troyer, Dean A.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [McKenney, Jesse K.] Cleveland Clin, Cleveland, OH 44106 USA. [Kunju, Priya; Wei, John T.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Lin, DW (reprint author), Univ Washington, Dept Urol, 1959 NE Pacific St,Box 356510, Seattle, WA 98195 USA. EM dlin@uw.edu FU Canary Foundation; National Cancer Institute at the National Institutes of Health Early Detection Research Network [U01 CA086402]; National Institutes of Health [P30 CA054174]; National Institutes of Health (Pacific Northwest Prostate Cancer SPORE) [P50 CA097186] FX Supported by the Canary Foundation; the National Cancer Institute at the National Institutes of Health Early Detection Research Network (Grant U01 CA086402); and the National Institutes of Health (Grant P30 CA054174, and the Pacific Northwest Prostate Cancer SPORE P50 CA097186). NR 27 TC 15 Z9 15 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD FEB PY 2016 VL 195 IS 2 BP 313 EP 320 DI 10.1016/j.juro.2015.08.087 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA DA8KZ UT WOS:000368054800023 PM 26327354 ER PT J AU Gelpi-Hammerschmidt, F Tinay, I Allard, CB Su, LM Preston, MA Trinh, QD Kibel, AS Wang, Y Chung, BI Chang, SL AF Gelpi-Hammerschmidt, Francisco Tinay, Ilker Allard, Christopher B. Su, Li-Ming Preston, Mark A. Quoc-Dien Trinh Kibel, Adam S. Wang, Ye Chung, Benjamin I. Chang, Steven L. TI The Contemporary Incidence and Sequelae of Rhabdomyolysis Following Extirpative Renal Surgery: A Population Based Analysis SO JOURNAL OF UROLOGY LA English DT Article DE rhabdomyolysis; kidney; surgical procedures; operative; population groups ID SURGICAL-PROCEDURES; BARIATRIC SURGERY; FLANK POSITION; UNITED-STATES; RISK-FACTORS; COMPLICATIONS; FAILURE; CLASSIFICATION; NEPHRECTOMY; COSTS AB Purpose: We evaluate the contemporary incidence and consequences of postoperative rhabdomyolysis after extirpative renal surgery. Materials and Methods: We conducted a population based, retrospective cohort study of patients who underwent extirpative renal surgery with a diagnosis of a renal mass or renal cell carcinoma in the United States between 2004 and 2013. Regression analysis was performed to evaluate 90-day mortality (Clavien grade V), nonfatal major complications (Clavien grade III-IV), hospital readmission rates, direct costs and length of stay. Results: The final weighted cohort included 310,880 open, 174,283 laparoscopic and 69,880 robotic extirpative renal surgery cases during the 10-year study period, with 745 (0.001%) experiencing postoperative rhabdomyolysis. The presence of postoperative rhabdomyolysis led to a significantly higher incidence of 90-day nonfatal major complications (34.7% vs 7.3%, p < 0.05) and higher 90-day mortality (4.4% vs 1.02%, p < 0.05). Length of stay was twice as long for patients with postoperative rhabdomyolysis (incidence risk ratio 1.83, 95% CI 1.56e2.15, p < 0.001). The robotic approach was associated with a higher likelihood of postoperative rhabdomyolysis (vs laparoscopic approach, OR 2.43, p < 0.05). Adjusted 90-day median direct hospital costs were USD 7,515 higher for patients with postoperative rhabdomyolysis (p < 0.001). Our model revealed that the combination of obesity and prolonged surgery (more than 5 hours) was associated with a higher likelihood of postoperative rhabdomyolysis developing. Conclusions: Our study confirms that postoperative rhabdomyolysis is an uncommon complication among patients undergoing extirpative renal surgery, but has a potentially detrimental impact on surgical morbidity, mortality and costs. Male gender, comorbidities, obesity, prolonged surgery (more than 5 hours) and a robotic approach appear to place patients at higher risk for postoperative rhabdomyolysis. C1 [Gelpi-Hammerschmidt, Francisco; Tinay, Ilker; Allard, Christopher B.; Preston, Mark A.; Quoc-Dien Trinh; Kibel, Adam S.; Chang, Steven L.] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Quoc-Dien Trinh; Wang, Ye; Chang, Steven L.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Gelpi-Hammerschmidt, Francisco; Allard, Christopher B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Tinay, Ilker] Marmara Univ, Sch Med, Dept Urol, Istanbul, Turkey. [Su, Li-Ming] Univ Florida, Coll Med, Dept Urol, Gainesville, FL USA. [Chung, Benjamin I.] Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA. RP Tinay, I (reprint author), Brigham & Womens Hosp, Div Urol, 45 Francis St, Boston, MA 02115 USA. EM itinay@partners.org FU Society of Urological Surgery in Turkey Scholarship Program; Kidney Cancer SPORE Career Development Award [5P50CA101942-09] FX Supported by the Society of Urological Surgery in Turkey Scholarship Program.; Supported by a Kidney Cancer SPORE Career Development Award (5P50CA101942-09). NR 29 TC 3 Z9 3 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD FEB PY 2016 VL 195 IS 2 BP 399 EP 405 DI 10.1016/j.juro.2015.08.084 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DA8KZ UT WOS:000368054800052 PM 26321407 ER PT J AU Rosand, J Mitchell, BD Ay, H de Bakker, PIW Gwinn, K Kittner, SJ Lindgren, A Meschia, JF Pulit, SL Sudlow, CLM Thijs, V Woo, D Worrall, BB Arnett, DK Benavente, O Cole, JW Dichgans, M Grewal, RP Jern, C Conde, JJ Johnson, JA Kittner, SJ Lee, JM Levi, C Lindgren, A Markus, HS Melander, O Meschia, JF Rexrode, K Rosand, J Rothwell, PM Rundek, T Sacco, RL Schmidt, R Sharma, P Slowik, A Sudlow, CLM Thijs, V Wasssertheil-Smoller, S Woo, D Worrall, BB AF Rosand, Jonathan Mitchell, Braxton D. Ay, Hakan de Bakker, Paul I. W. Gwinn, Katrina Kittner, Steven J. Lindgren, Arne Meschia, James F. Pulit, Sara L. Sudlow, Cathie L. M. Thijs, Vincent Woo, Daniel Worrall, Bradford B. Arnett, Donna K. Benavente, Oscar Cole, John W. Dichgans, Martin Grewal, Raji P. Jern, Christina Conde, Jordi Jimenez Johnson, Julie A. Kittner, Steven J. Lee, Jin-Moo Levi, Christopher Lindgren, Arne Markus, Hugh S. Melander, Olle Meschia, James F. Rexrode, Kathryn Rosand, Jonathan Rothwell, Peter M. Rundek, Tatjana Sacco, Ralph L. Schmidt, Reinhold Sharma, Pankaj Slowik, Agnieszka Sudlow, Cathie L. M. Thijs, Vincent Wasssertheil-Smoller, Sylvia Woo, Daniel Worrall, Bradford B. CA NINDS Stroke Genetics Network SiGN ISGC TI Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study SO LANCET NEUROLOGY LA English DT Article ID CAUSATIVE CLASSIFICATION; ATRIAL-FIBRILLATION; GENETICS NETWORK; COMMON VARIANTS; METAANALYSIS; REPLICATION; POPULATION; IMPUTATION; SYSTEM; TOAST AB Background The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes. Methods To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16 851 cases with state-of-the-art phenotyping data and 32 473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20 941 cases and 364 736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis. Findings We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1.21, 95% CI 1.13-1.30, p=4.50 x 10(-8); joint OR 1.19, 1.12-1.26, p=1.30 x 10(-9)). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1.39, 1.29-1.49, p=3.26 x 10(-1).; joint OR 1.37, 1.30-1.45, p= 2.79 x 10(-32)) and ZFHX3 (fi rst stage OR 1.19, 1.11-1.27, p=2.93 x 10(-7); joint OR 1.17, 1.11-1.23, p=2.29 x 10(-10)) for cardioembolic stroke, and HDAC9 (first stage OR 1.29, 1.18-1.42, p=3.50 x 10(-8); joint OR 1.24, 1.15-1.33, p= 4.52 x 10(-9)) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (fi rst stage OR 1.20, 1.12-1.28, p=6.82 x 10(-8); joint OR 1.17, 1.11-1.23, p=2.92 x 10(-9)). Other loci associat ed with stroke in previous studies, including NINJ2, were not confirmed. Interpretation Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke. C1 [Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RI JIMENEZ-CONDE, JORDI/C-1941-2012; rabionet, raquel/C-8379-2009; Boncoraglio, Giorgio/B-8647-2011; Thijs, Vincent/C-3647-2009; OI rabionet, raquel/0000-0001-5006-8140; Thijs, Vincent/0000-0002-6614-8417; Williams, Stephen/0000-0003-2108-2757; Rexrode, Kathryn/0000-0003-3387-8429; Mitchell, Braxton/0000-0003-4920-4744; Tajuddin, Salman M./0000-0002-7919-8528 FU US National Institute of Neurological Disorders and Stroke, National Institutes of Health FX US National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 35 TC 5 Z9 5 U1 4 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD FEB PY 2016 VL 15 IS 2 BP 174 EP 184 DI 10.1016/S1474-4422(15)00338-5 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA DA9GC UT WOS:000368116000015 ER PT J AU Hunsberger, JG Rao, M Kurtzberg, J Bulte, JWM Atala, A LaFerla, FM Greely, HT Sawa, A Gandy, S Schneider, LS Doraiswamy, PM AF Hunsberger, Joshua G. Rao, Mahendra Kurtzberg, Joanne Bulte, Jeff W. M. Atala, Anthony LaFerla, Frank M. Greely, Henry T. Sawa, Akira Gandy, Sam Schneider, Lon S. Doraiswamy, P. Murali TI Accelerating stem cell trials for Alzheimer's disease SO LANCET NEUROLOGY LA English DT Article ID UMBILICAL-CORD BLOOD; IPSC-DERIVED NEURONS; PARKINSONS-DISEASE; A-BETA; REGENERATIVE MEDICINE; PEDIATRIC-PATIENTS; INFORMED-CONSENT; DRUG-DEVELOPMENT; MOUSE MODELS; AMYLOID-BETA AB At present, no effective cure or prophylaxis exists for Alzheimer's disease. Symptomatic treatments are modestly effective and off er only temporary benefit. Advances in induced pluripotent stem cell (iPSC) technology have the potential to enable development of so-called disease-in-a-dish personalised models to study disease mechanisms and reveal new therapeutic approaches, and large panels of iPSCs enable rapid screening of potential drug candidates. Different cell types can also be produced for therapeutic use. In 2015, the US Food and Drug Administration granted investigational new drug approval for the first phase 2A clinical trial of ischaemia-tolerant mesenchymal stem cells to treat Alzheimer's disease in the USA. Similar trials are either underway or being planned in Europe and Asia. Although safety and ethical concerns remain, we call for the acceleration of human stem cell-based translational research into the causes and potential treatments of Alzheimer's disease. C1 [Hunsberger, Joshua G.; Atala, Anthony] Wake Forest Univ, Wake Forest Inst Regenerat Med, Winston Salem, NC 27109 USA. [Rao, Mahendra] New York Stem Cell Fdn, New York, NY USA. [Kurtzberg, Joanne] Duke Univ, Med Ctr, Robertson Clin & Translat Cell Therapy Program, Durham, NC USA. [Bulte, Jeff W. M.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Bulte, Jeff W. M.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD USA. [Sawa, Akira] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [LaFerla, Frank M.] Univ Calif Irvine, Inst Memory Impairment & Neurol Disorders, Irvine, CA USA. [Greely, Henry T.] Stanford Univ, Ctr Law & Biosci, Stanford, CA 94305 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Ctr Cognit Hlth, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Natl Football League Neurol Care, New York, NY 10029 USA. [Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Alzheimers Dis Res Ctr, Los Angeles, CA 90033 USA. [Doraiswamy, P. Murali] Duke Univ, Duke Inst Brain Sci, Durham, NC USA. [Doraiswamy, P. Murali] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. RP Hunsberger, JG (reprint author), Wake Forest Univ, Wake Forest Inst Regenerat Med, Winston Salem, NC 27109 USA. FU Accelerated Medicines Partnership [U01 AG046170]; David Werber Family Trust; Cure Alzheimer's Fund; Veterans Affairs [I01RX000684]; US National Institutes of Health; National Multiple Sclerosis Society; ALS Association; Maryland Stem Cell Research Fund; Brain & Behavior Research Foundation; Stanley Foundation; RUSK Foundation; Maryland Stem Cell Research Funds FX We acknowledge the contributions of all faculty members and participants at our meeting for the valuable discussions. We are especially grateful for the support of Marjorie Bekaert Thomas, Trustee for the Karen L Wrenn Trust, whose vision led to this conference. The meeting on stem cells and Alzheimer's disease, and the writing of this Personal View, was funded by a gift from the Karen L Wrenn Trust to PMD through Duke University. The Trust had no input in the content of this Personal View. We also acknowledge support from Accelerated Medicines Partnership/U01 AG046170, the David Werber Family Trust, the Cure Alzheimer's Fund, and Veterans Affairs (grant I01RX000684) (all to SG). JWMB, PMD, and AS have been supported by grants from the US National Institutes of Health. JWMB is also supported by the National Multiple Sclerosis Society, the ALS Association, and the Maryland Stem Cell Research Fund. AS reports receiving grants from the Brain & Behavior Research Foundation (formerly the NARSAD), Stanley Foundation, RUSK Foundation, and Maryland Stem Cell Research Funds during the writing of the manuscript. Figure 1 is courtesy of Piotr Walczak and Miroslaw Janowski, Johns Hopkins University, Baltimore, MD, USA. NR 92 TC 3 Z9 4 U1 7 U2 52 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD FEB PY 2016 VL 15 IS 2 BP 219 EP 230 DI 10.1016/S1474-4422(15)00332-4 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA DA9GC UT WOS:000368116000019 ER PT J AU Yu, JT Zhang, C AF Yu, Jin-Tai Zhang, Can TI Pathogenesis and Therapeutic Strategies in Alzheimer's Disease: From Brain to Periphery SO NEUROTOXICITY RESEARCH LA English DT Editorial Material DE Alzheimer's disease; Amyloid-beta; Periphery; Pathogenesis; Therapy ID PLASMA A-BETA; AMYLOID-BETA; MOUSE MODEL; CLEARANCE; NEPRILYSIN; PROGRESS; BURDEN; MICE AB Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder. At present, there are no effective disease-modifying therapies, and the cause of the disease remains unclear. Previously, almost all researchers focus on the brain for exploring the pathogenesis and therapeutic strategies in AD. A recent study by Xiang et al. (Acta Neuropathol 130:487-499, 2015) reported the significance of the physiological capacity of peripheral tissues and organs in clearing brain-derived amyloid-beta (A beta), which opens a novel avenue to understand the AD pathogenesis and develop therapies for AD. C1 [Yu, Jin-Tai] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94158 USA. [Zhang, Can] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. [Zhang, Can] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Yu, JT (reprint author), Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, 675 Nelson Rising Lane,Suite 190,Box 1207, San Francisco, CA 94158 USA. EM jintai.yu@ucsf.edu NR 21 TC 0 Z9 1 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 EI 1476-3524 J9 NEUROTOX RES JI Neurotox. Res. PD FEB PY 2016 VL 29 IS 2 BP 197 EP 200 DI 10.1007/s12640-015-9576-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA DB0JK UT WOS:000368194200001 PM 26597964 ER PT J AU Itagaki, T Gubin, TA Sayal, P Jiang, YD Kacmarek, RM Anderson, TA AF Itagaki, Taiga Gubin, Tatyana A. Sayal, Puneet Jiang, Yandong Kacmarek, Robert M. Anderson, Thomas Anthony TI The effectiveness of nasal mask vs face mask ventilation in anesthetized, apneic pediatric subjects over 2years of age: a randomized controlled trial SO PEDIATRIC ANESTHESIA LA English DT Article DE airway management; airway obstruction; anesthesia; pediatrics; mask; ventilators; mechanical ID UPPER AIRWAY COLLAPSIBILITY; NONINVASIVE VENTILATION; INTUBATION; ANESTHESIA; PRESSURE; CHILDREN; SLEEP; PREOXYGENATION AB Background: We hypothesized that anesthetized, apneic children could be ventilated equivalently or more efficiently by nasal mask ventilation ( NMV) than face mask ventilation ( FMV). The aim of this randomized controlled study was to test this hypothesis by comparing the expiratory tidal volume ( Vte) between NMV and FMV. Methods: After the induction of anesthesia, 41 subjects, 3- 17 years of age without anticipated difficult mask ventilation, were randomly assigned to receive either NMV or FMV with neck extension. Both groups were ventilated with pressure control ventilation ( PCV) at 20 cmH2O of peak inspiratory pressure ( PIP) with positive end- expiratory pressure ( PEEP) levels of 0, 5, and 10 cmH2O. An additional mouth closing maneuver ( MCM) was applied for the NMV group. Results: The Vte was higher in the FMV group compared with the NMV group ( median difference [ 95% CI]: 8.4 [ 5.5- 11.6] ml kg -1; P < 0.001) when MCM was not applied. NMV achieved less PEEP than FMV ( median difference [ 95% CI]: 5.0 [ 4.3- 5.3] cmH2O at 10 cmH2O; P < 0.001) though both groups achieved the set PIP level. In the NMV group, MCM markedly increased Vte ( median increase [ 95% CI]: 5.9 [ 2.5- 9.0] ml kg -1; P < 0.005) and PEEP ( median increase [ 95% CI]: 5.0 [ 0.6- 8.6] cmH(2)O at 10 cmH(2)O; P < 0.005); however, PEEP was highly variable and lower than that of FMV ( median difference [ 95% CI]: 2.5 [ 0.8- 8.5] cmH2O at 10 cmH2O; P < 0.05). Conclusions: In anesthetized, apneic children greater than 2 years of age ventilated with an anesthesia ventilator and neck extension, FMV established a greater Vte than NMV regardless of mouth status. NMV could not maintain the set PEEP level due to an air leak from the mouth. The MCM increased the Vte and PEEP. C1 [Itagaki, Taiga; Gubin, Tatyana A.; Sayal, Puneet; Kacmarek, Robert M.; Anderson, Thomas Anthony] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Itagaki, Taiga; Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Gubin, Tatyana A.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Jiang, Yandong] Vanderbilt Univ Sch Med, Dept Anesthesia, Nashville, TN USA. RP Anderson, TA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM tanderson9@mgh.harvard.edu FU Covidien; Venner Medical FX The study protocol was approved by the Massachusetts General Hospital Human Research Committee (Boston, MA, USA). This study work was supported only by departmental sources. RM Kacmarek received research grants from Covidien and Venner Medical. RM Kacmarek is a consultant for Covidien and received honorarium for one lecture per year from Maquet. The other authors disclose no conflict of interest. NR 24 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 EI 1460-9592 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD FEB PY 2016 VL 26 IS 2 BP 173 EP 181 DI 10.1111/pan.12822 PG 9 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA DA4RT UT WOS:000367788700008 PM 26725988 ER PT J AU Johansen, T Winkler, T Kelly, VJ Osorio-Valencia, JS Greenblatt, EE Harris, RS Venegas, JG AF Johansen, Troels Winkler, Tilo Kelly, Vanessa Jane Osorio-Valencia, Juan Sebastian Greenblatt, Elliot Eliyahu Harris, Robert Scott Venegas, Jose Gabriel TI A method for mapping regional oxygen and CO2 transfer in the lung SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article DE Pulmonary gas exchange; Lung imaging; O-2 uptake; CO2 elimination; Ventilation/perfusion; Asthma ID VENTILATION-PERFUSION INEQUALITY; HYPERPOLARIZED HE-3 MRI; GAS-EXCHANGE; STATUS ALGORITHM; MATHEMATICAL-MODEL; PARTIAL-PRESSURE; BLOOD; ASTHMA; PET; PH AB This paper presents a novel approach to visualizing regional lung function, through quantitative three-dimensional maps of O-2 and CO2 transfer rates. These maps describe the contribution of anatomical regions to overall gas exchange and demonstrate how transfer rates of the two gas species' differ regionally. An algorithm for generating such maps is presented, and for illustration, regional gas transfer maps were generated using values of ventilation and perfusion imaged by PET/CT for a healthy subject and an asthmatic patient after bronchoprovocation. In a sensitivity analysis, compartment values of gas transfer showed minor sensitivity to imaging noise in the ventilation and perfusion data, and moderate sensitivity to estimation errors in global lung input values, chiefly global alveolar ventilation, followed by cardiac output and arterial-venous O-2 content difference. Gas transfer maps offer an intuitive display of physiologically relevant lung function at a regional level, the potential for an improved understanding of pulmonary gas exchange in health and disease, and potentially a presurgical evaluation tool. (C) 2015 Elsevier B.V. All rights reserved. C1 [Johansen, Troels] Aarhus Univ Hosp, Dept Resp Dis, DK-8000 Aarhus C, Denmark. [Johansen, Troels; Winkler, Tilo; Kelly, Vanessa Jane; Osorio-Valencia, Juan Sebastian; Greenblatt, Elliot Eliyahu; Venegas, Jose Gabriel] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Johansen, Troels; Winkler, Tilo; Kelly, Vanessa Jane; Osorio-Valencia, Juan Sebastian; Greenblatt, Elliot Eliyahu; Venegas, Jose Gabriel] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Osorio-Valencia, Juan Sebastian] Tech Univ Munich, Dept Informat, D-85748 Garching, Germany. [Greenblatt, Elliot Eliyahu] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Harris, Robert Scott] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Johansen, T (reprint author), Aarhus Univ Hosp, Dept Resp Dis, Noerrebrogade 44,Byg 2B kld, DK-8000 Aarhus C, Denmark. EM troels.johansen@clin.au.dk RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU NIH [HL68011] FX The PET/CT data acquisition was sponsored by NIH grant HL68011. NR 45 TC 3 Z9 3 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 EI 1878-1519 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD FEB 1 PY 2016 VL 222 BP 29 EP 47 DI 10.1016/j.resp.2015.10.017 PG 19 WC Physiology; Respiratory System SC Physiology; Respiratory System GA DB0OY UT WOS:000368208600005 PM 26563454 ER PT J AU Marti, JL Holm, T Randolph, G AF Marti, Jennifer L. Holm, Tammy Randolph, Gregory TI Universal Use of Intraoperative Nerve Monitoring by Recently Fellowship-Trained Thyroid Surgeons is Common, Associated with Higher Surgical Volume, and Impacts Intraoperative Decision-Making SO WORLD JOURNAL OF SURGERY LA English DT Article ID RECURRENT LARYNGEAL NERVE; METAANALYSIS; VISUALIZATION; PREVALENCE; PATTERNS; INJURY AB The value of routine use of intraoperative recurrent laryngeal nerve monitoring (IONM) in thyroid surgery is controversial. We analyzed the practices of recently fellowship-trained thyroid surgeons from two diverging surgical backgrounds with respect to IONM. We hypothesized that the majority of recently trained surgeons would use IONM, and that it would potentially influence their operative procedure. A 21-question survey was sent to 56 fellowship-trained endocrine and head and neck surgeons who completed fellowships accredited by the American Association of Endocrine Surgeons or American Head and Neck Society within the past 10 years, examining the demographics of respondents, and details of IONM practice. Groups were compared using the Fisher exact and chi (2) tests. The response rate for the survey was 76 % (42/56). Overall, 95 % use IONM for some or all of their cases. Sixty percent (n = 25) of respondents always use IONM during thyroid surgery, 36 % (n = 15) use it selectively, and 5 % (n = 2) never use it. We compared respondents who always use IONM (n = 25), to those who selectively or never use it (n = 17). Exposure to IONM during residency or fellowship did not influence use (p = 0.99). However, higher-volume surgeons were more likely to always use IONM (p = 0.036). Among users of IONM, the most common reason given for use was increased surgeon confidence (55 %) and improved safety (54 %). Over 90 % of respondents found reoperative cases and preoperative vocal cord paralysis to be indications for IONM. Among those who always used IONM, 64 % would alter extent of surgery based on IONM findings, compared to only 27 % of selective users. A survey of recently trained endocrine and head and neck surgeons reveals that the vast majority (95 %) of these surgeons commonly use IONM during thyroid surgery. IONM was more commonly used by higher-volume surgeons. Routine users were more likely to modify surgery based on nerve integrity (i.e., not complete a total thyroidectomy if the nerve loses conduction signal). C1 [Marti, Jennifer L.] Icahn Sch Med Mt Sinai, Mt Sinai Beth Israel, Dept Surg, Div Endocrine Surg, New York, NY 10003 USA. [Holm, Tammy; Randolph, Gregory] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Surg Serv,Dept Surg, Boston, MA 02115 USA. [Randolph, Gregory] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Div Thyroid & Parathyroid Endocrine Surg, Boston, MA 02115 USA. RP Marti, JL (reprint author), Icahn Sch Med Mt Sinai, Mt Sinai Beth Israel, Dept Surg, Div Endocrine Surg, 10 Union Sq East,Suite 4E11, New York, NY 10003 USA. EM jmarti@chpnet.org NR 19 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD FEB PY 2016 VL 40 IS 2 BP 337 EP 343 DI 10.1007/s00268-015-3238-7 PG 7 WC Surgery SC Surgery GA DA8TI UT WOS:000368078700013 PM 26330239 ER PT J AU Sise, ME Bloom, AK Wisocky, J Lin, MV Gustafson, JL Lundquist, AL Steele, D Thiim, M Williams, WW Hashemi, N Kim, AY Thadhani, R Chung, RT AF Sise, Meghan E. Bloom, Allyson K. Wisocky, Jessica Lin, Ming V. Gustafson, Jenna L. Lundquist, Andrew L. Steele, David Thiim, Michael Williams, Winfred W. Hashemi, Nikroo Kim, Arthur Y. Thadhani, Ravi Chung, Raymond T. TI Treatment of Hepatitis C Virus-Associated Mixed Cryoglobulinemia with Direct-Acting Antiviral Agents SO HEPATOLOGY LA English DT Article ID ALPHA/RIBAVIRIN/PROTEASE INHIBITOR COMBINATION; GENOTYPE 1; INFECTION; THERAPY; SOFOSBUVIR; VASCULITIS; RITUXIMAB; GLOMERULONEPHRITIS; INTERFERON; RIBAVIRIN AB Hepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral direct-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. The authors studied case series of patients with HCV-MCS who were treated with sofosbuvir-based regimens and historical controls treated with pegylated interferon and ribavirin in a single health care network. HCV-MCS was defined by circulating cryoglobulin associated with systemic vasculitis symptoms. Renal involvement (n = 7) was established by kidney biopsy (n = 5) or by two or more of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (n = 2). Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% were male, and 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7-2.47). Four patients received rituximab concurrent with DAA therapy. Sustained virological response rate at 12 weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and a reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5% and completely disappearing in four of nine cases who had cryoglobulins measured after treatment. Serious adverse events were infrequent (17%). In contrast, the historical cohort treated with pegylated interferon and ribavirin experienced only 10% SVR12, with 100% experiencing at least one adverse event and 50% experiencing premature discontinuation due to adverse events. Conclusion: SVR12 rates for sofosbuvir-based DAA regimens in HCV-MCS were 83%, significantly higher than historical controls treated with pegylated interferon and ribavirin; patients with glomerulonephritis experienced improvement in renal function, including those not concomitantly treated with immunosuppression. C1 [Sise, Meghan E.; Lundquist, Andrew L.; Steele, David; Williams, Winfred W.; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Bloom, Allyson K.; Kim, Arthur Y.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Wisocky, Jessica; Gustafson, Jenna L.; Thiim, Michael; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Div, Ctr Liver, Boston, MA 02114 USA. [Lin, Ming V.; Hashemi, Nikroo] Brigham & Womens Hosp, Dept Med, Div Gastroenterol & Hepatol, 75 Francis St, Boston, MA 02115 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, GI Div, Ctr Liver, Warren 1007,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU NIH National Institutes of Health grants [K24 DK078772]; NIH [U19 AI082630]; ASN Foundation for Kidney Research FX Supported by NIH National Institutes of Health grants K24 DK078772 (to R.T.C.), NIH and U19 AI082630 (to R.T.C. and, A.Y.K.) and the, ASN Foundation for Kidney Research Fellows Award (to M.E.S.). NR 32 TC 19 Z9 21 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 FEB PY 2016 VL 63 IS 2 BP 408 EP 417 DI 10.1002/hep.28297 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EL6VS UT WOS:000394761100012 PM 26474537 ER PT J AU Gardner, RC Rabinovici, GD AF Gardner, Raquel C. Rabinovici, Gil D. TI Evaluating and treating neurobehavioral symptoms in professional American football players: Lessons from a case series Respond SO NEUROLOGY-CLINICAL PRACTICE LA English DT Letter C1 [Gardner, Raquel C.; Rabinovici, Gil D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gardner, Raquel C.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM raquel.gardner@ucsf.edu FU American Academy of Neurology; Alzheimer's Association; Department of Veterans Affairs; NIH/NIA; UCSF Pepper Center Research Career Development Core; GE Healthcare; Rockpointe; Tau Consortium; Medscape; Avid Radiopharmaceuticals/Eli Lilly; John Douglas French Alzheimer's Foundation; Hellman Family Foundation FX R.C. Gardner has received funding for travel from the American Academy of Neurology and the Alzheimer's Association and has received research support from the Department of Veterans Affairs, NIH/NIA, and UCSF Pepper Center Research Career Development Core. G.D. Rabinovici has received funding for travel and/or speaker honoraria from Alzheimer's Association, GE Healthcare, Rockpointe, Tau Consortium, and Medscape and receives research support from Avid Radiopharmaceuticals/Eli Lilly, NIH/NIA, Alzheimer's Association, John Douglas French Alzheimer's Foundation, Hellman Family Foundation, and Tau Consortium. 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 2163-0402 EI 2163-0933 J9 NEUROL-CLIN PRACT JI Neurol.-Clin. Pract. PD FEB PY 2016 VL 6 IS 1 BP 7 EP 8 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA EI6IT UT WOS:000392599600006 ER PT J AU Kraakevik, J AF Kraakevik, Jeff TI Crafting a positive professional digital profile to augment your practice SO NEUROLOGY-CLINICAL PRACTICE LA English DT Editorial Material AB A digital profile is the sum content about a person on the Internet. A digital profile can be composed of personal or professional information shared on public Web sites posted personally or by others. One of the most effective ways to build a positive professional digital profile is through social media. It is increasingly important to maintain a positive digital profile as others mine the Internet to find out about a professional prior to meeting him or her. As the digital environment continues to grow, it will become increasingly difficult to neglect a professional digital profile without potential negative consequences. There are many benefits to creating a digital presence and using the tools available to learn about neurology and interact with other professionals and patients in ways that were not possible in the past. The spread of social media to a large part of the population makes it unlikely to go away. C1 [Kraakevik, Jeff] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. EM kraakevik@ohsu.edu 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 2163-0402 EI 2163-0933 J9 NEUROL-CLIN PRACT JI Neurol.-Clin. Pract. PD FEB PY 2016 VL 6 IS 1 BP 87 EP 93 DI 10.1212/CPJ.0000000000000211 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA EI6IT UT WOS:000392599600024 ER PT J AU Karam, CY Paganoni, S Joyce, N Carter, GT Bedlack, R AF Karam, Chafic Y. Paganoni, Sabrina Joyce, Nanette Carter, Gregory T. Bedlack, Richard TI Palliative Care Issues in Amyotrophic Lateral Sclerosis: An Evidenced-Based Review SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Review DE amyotrophic lateral sclerosis; palliative care; hospice; alternative medicine; quality of life ID QUALITY STANDARDS SUBCOMMITTEE; PLASMA HOMOCYSTEINE LEVELS; PRACTICE PARAMETER UPDATE; TRANSGENIC MOUSE MODEL; BODY-MASS INDEX; DOUBLE-BLIND; VITAMIN-E; NEUROMUSCULAR DISEASE; CREATINE MONOHYDRATE; PULMONARY-FUNCTION AB As palliative care physicians become increasingly involved in the care of patients with amyotrophic lateral sclerosis (ALS), they will be asked to provide guidance regarding the use of supplements, diet, exercise, and other common preventive medicine interventions. Moreover, palliative care physicians have a crucial role assisting patients with ALS in addressing health care decisions to maximize quality of life and cope with a rapidly disabling disease. It is therefore important for palliative care physicians to be familiar with commonly encountered palliative care issues in ALS. This article provides an evidenced-based review of palliative care options not usually addressed in national and international ALS guidelines. C1 [Karam, Chafic Y.] Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA. [Paganoni, Sabrina] Harvard Univ, Massachusetts Gen Hosp, Spaulding Rehabil Hosp, Cambridge, MA 02138 USA. [Paganoni, Sabrina] Boston VA Healthcare Syst, Boston, MA USA. [Joyce, Nanette] Calif State Univ Sacramento, Davis Med Sch, Dept Phys Med & Rehabil, Neuromusc Sect, Sacramento, CA 95819 USA. [Carter, Gregory T.] St Lukes Rehabil Inst, Dept Phys Med & Rehabil, Spokane, WA USA. [Bedlack, Richard] Duke Univ, Sch Med, Durham, NC USA. [Bedlack, Richard] Durham Vet Affairs Med Ctr, Durham, NC USA. RP Karam, CY (reprint author), Univ N Carolina, Dept Neurol, Campus Box 7025, Chapel Hill, NC 27599 USA. EM chafickaram@gmail.com FU NICHD NIH HHS [K12 HD001097] NR 77 TC 1 Z9 1 U1 3 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD FEB PY 2016 VL 33 IS 1 BP 84 EP 92 DI 10.1177/1049909114548719 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DA3UT UT WOS:000367725300013 PM 25202033 ER PT J AU Spencer, NY Yan, ZY Cong, L Zhang, YL Engelhardt, JF Stanton, RC AF Spencer, Netanya Y. Yan, Ziying Cong, Le Zhang, Yulong Engelhardt, John F. Stanton, Robert C. TI Definitive localization of intracellular proteins: Novel approach using CRISPR-Cas9 genome editing, with glucose 6-phosphate dehydrogenase as a model SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Glucose 6-phosphate dehydrogenase; CRISPR-Cas9 genome engineering; Nuclear localization signal; Knockout cell lines; Dimer; Multimer ID GREEN FLUORESCENT PROTEIN; NUCLEAR-LOCALIZATION; MAMMALIAN-CELLS; ENZYME-CYTOCHEMISTRY; CAS9; SPECIFICITY; REVEALS; BINDING AB Studies to determine subcellular localization and translocation of proteins are important because subcellular localization of proteins affects every aspect of cellular function. Such studies frequently utilize mutagenesis to alter amino acid sequences hypothesized to constitute subcellular localization signals. These studies often utilize fluorescent protein tags to facilitate live cell imaging. These methods are excellent for studies of monomeric proteins, but for multimeric proteins, they are unable to rule out artifacts from native protein subunits already present in the cells. That is, native monomers might direct the localization of fluorescent proteins with their localization signals obliterated. We have developed a method for ruling out such artifacts, and we use glucose 6-phosphate dehydrogenase (G6PD) as a model to demonstrate the method's utility. Because G6PD is capable of homodimerization, we employed a novel approach to remove interference from native G6PD. We produced a G6PD knockout somatic (hepatic) cell line using CRISPR-Cas9 mediated genome engineering. Transfection of G6PD knockout cells with G6PD fluorescent mutant proteins demonstrated that the major subcellular localization sequences of G6PD are within the N-terminal portion of the protein. This approach sets a new gold standard for similar studies of subcellular localization signals in all homodimerization-capable proteins. (C) 2015 Elsevier Inc. All rights reserved. C1 [Spencer, Netanya Y.; Stanton, Robert C.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Spencer, Netanya Y.; Stanton, Robert C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yan, Ziying; Zhang, Yulong; Engelhardt, John F.] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Cong, Le] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Stanton, Robert C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Spencer, NY (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM netanya.spencer@joslin.harvard.edu FU University of Iowa Roy J. Carver Chair in Molecular Medicine; National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK051315, K01 DK083429] FX This work was supported by the University of Iowa Roy J. Carver Chair in Molecular Medicine, and the National Institute of Diabetes and Digestive and Kidney Diseases Grants R01 DK051315 (to JFE) and K01 DK083429 (to NYS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare that they have no competing interests. Although we did not make use of HeLa-specific genome data, we did use a HeLa cell line in this project, and we wish to acknowledge our sincere gratitude to Henrietta Lacks, now deceased, and her surviving family members for their contributions to biomedical research. NR 30 TC 2 Z9 3 U1 4 U2 40 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 1 PY 2016 VL 494 BP 55 EP 67 DI 10.1016/j.ab.2015.11.002 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA DA4HV UT WOS:000367761900012 PM 26576833 ER PT J AU Albergotti, WG Byrd, JK Nance, M Choi, EC Koh, YW Kim, S Duvvuri, U AF Albergotti, William G. Byrd, James K. Nance, Melonie Choi, Eun Chang Koh, Yoon Woo Kim, Seungwon Duvvuri, Umamaheswar TI Robot-Assisted Neck Dissection Through a Modified Facelift Incision SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE head and neck squamous cell carcinoma; head and neck surgery; neck dissection; surgical outcomes; treatment of head and neck tumors ID SQUAMOUS-CELL-CARCINOMA; POSTOPERATIVE MORBIDITY; RETROAURICULAR APPROACH; ORAL-CAVITY; HEAD; SURGERY; CANCER; LYMPHEDEMA; PAROTIDECTOMY; EXPERIENCE AB Objectives: The aim of this study is to describe the feasibility as well as oncologic outcomes of robot-assisted neck dissection (RAND) through a modified facelift incision in an American population. Study Design: Retrospective case series. Setting: University tertiary care hospital. Methods: All patients who underwent RAND between November 2012 and December 2014 were included. Medical records were reviewed for demographics, medical histories, staging, operative information, postoperative hospital course and complications, and oncologic outcomes. Results: There were 11 RANDs identified among 10 patients. Five patients had known nodal metastasis at the time of surgery. Two patients had been previously irradiated. The average time of surgery was 284.4 72.3 minutes, including other associated procedures. The average lymph node yield was 28.5 +/- 9.3 nodes. There were no major complications. Average follow-up was 19.4 months. There was 1 supraclavicular recurrence in a previously irradiated patient. All patients are currently alive and without evidence of disease. Conclusions: Robot-assisted neck dissection is a safe and feasible procedure that can be performed by surgeons with familiarity with neck dissection and robot-assisted surgery and who have been trained in RAND. Appropriate oncologic outcomes can be obtained in a patient wishing to avoid a noticeable scar. C1 [Albergotti, William G.; Byrd, James K.; Nance, Melonie; Kim, Seungwon; Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Nance, Melonie; Duvvuri, Umamaheswar] Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Choi, Eun Chang; Koh, Yoon Woo] Yonsei Univ, Dept Otorhinolaryngol, Coll Med, Seoul, South Korea. RP Duvvuri, U (reprint author), Univ Pittsburgh, Inst Eye & Ear, Dept Otolaryngol, Med Ctr, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA. EM duvuriu@upmc.edu FU Intuitive Surgical, Inc.; Department of Veterans Affairs BLRD; PNC Foundation FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dr Byrd was funded by a clinical robotics training and research grant from Intuitive Surgical, Inc. This work was supported in part by a Career Development Award from the Department of Veterans Affairs BLR&D and the PNC Foundation (U.D). NR 29 TC 0 Z9 0 U1 1 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-4894 EI 1943-572X J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD FEB PY 2016 VL 125 IS 2 BP 123 EP 129 DI 10.1177/0003489415601127 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA DA5NM UT WOS:000367849800004 PM 26282589 ER PT J AU Yao, WC Bleier, BS AF Yao, William C. Bleier, Benjamin S. TI Endoscopic management of orbital tumors SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY LA English DT Review DE endoscopic orbital surgery; endoscopic surgery; intraorbital tumor resection; nasoseptal flap; orbital tumor ID TRANSETHMOIDAL APPROACH; APEX; LESIONS; RECONSTRUCTION; HEMANGIOMAS; SURGERY; ANATOMY; MUSCLE; SINUS; FLAP AB Purpose of reviewOrbital tumors have been classically approached via external incision. The introduction of endoscopic surgery has revolutionized the management of sinus and skull base disorder. Similarly, endoscopic techniques have been increasingly utilized to access intraorbital tumors located in the medial and inferior orbit with excellent outcomes. The history of the procedure, surgical anatomy of the orbit, patient selection, surgical planning, and the surgical techniques are discussed in this article. Recent findingsAlthough the endoscopic management of orbital tumors is still in its infancy, it has already demonstrated enhanced access to the posterior orbit and orbital apex with decreased morbidity relative to external approaches. SummaryA multidisciplinary team approach, including an oculoplastic surgeon, is an essential component for the surgical planning and management. As the cumulative surgical experience increases, the indications for this approach will likely continue to expand. C1 [Yao, William C.] Univ Texas Houston, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Houston, TX 77030 USA. [Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. RP Yao, WC (reprint author), Univ Texas Houston, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, 6431 Fannin St,MSB 5-036, Houston, TX 77030 USA. EM William.c.yao@uth.tmc.edu FU Massachusetts Eye and Ear Infirmary FX B.S.B. is a consultant for Arthrocare, Gyrus Olympus, and Karl Storz, and may receive royalties from Massachusetts Eye and Ear Infirmary. W.C.Y has no conflicts of interest. NR 23 TC 1 Z9 1 U1 6 U2 9 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 FEB PY 2016 VL 24 IS 1 BP 57 EP 62 DI 10.1097/MOO.0000000000000215 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA DA2BC UT WOS:000367599300011 PM 26575515 ER PT J AU Bishop, MW Janeway, KA Gorlick, R AF Bishop, Michael W. Janeway, Katherine A. Gorlick, Richard TI Future directions in the treatment of osteosarcoma SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE genomic complexity; immunotherapy; osteosarcoma; targeted therapy; TP53 ID HIGH-GRADE OSTEOSARCOMA; PRECLINICAL TESTING PROGRAM; CHILDRENS ONCOLOGY GROUP; METASTATIC OSTEOSARCOMA; MURAMYL TRIPEPTIDE; ANTIBODY BLOCKADE; STAGE 1; SORAFENIB; SURVIVAL; TRIAL AB Purpose of reviewOverall survival rates for osteosarcoma have remained essentially unchanged over the past 3 decades despite attempts to improve outcome via dose intensification and modification based on response. This review describes recent findings from contemporary clinical trials, advances in the comprehension of osteosarcoma biology and genomic complexity, and potential opportunities using targeted and immune-mediated therapies.Recent findingsRecent results from international collaborative trials have failed to demonstrate an ability to improve outcomes using a design in which the randomized question is dictated based on histologic response to preoperative chemotherapy. Novel prognostic markers assessable at diagnosis are vital to identifying subsets of osteosarcoma. Clinical trials focus has now shifted to serial phase II studies of novel agents to evaluate for activity in recurrent and refractory disease. In-depth analyses have revealed profound genomic instability and heterogeneity across patients, with nearly universal TP53 aberration. Although driver mutational events have not clearly been established, frequent derangements in specific pathways may suggest opportunities for therapeutic exploitation. Genomic complexity may lend support to a role for immune-mediated therapies.SummaryRigorous preclinical investigations are potentially generating novel strategies for the treatment of osteosarcoma that will inform the next generation of clinical trials, with the opportunity to identify agents that will improve survival outcomes. C1 [Bishop, Michael W.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Bishop, Michael W.] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. [Janeway, Katherine A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gorlick, Richard] Childrens Hosp Montefiore, Div Pediat Hematol Oncol, Bronx, NY USA. RP Gorlick, R (reprint author), Childrens Hosp Montefiore, 3415 Bainbridge Ave,Rosenthal Pavil,Room 300, Bronx, NY 10467 USA. EM rgorlick@montefiore.org FU NCATS NIH HHS [UL1 TR001425]; NCI NIH HHS [U01 CA199221, P30 CA013330] NR 47 TC 2 Z9 4 U1 4 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8703 EI 1531-698X J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD FEB PY 2016 VL 28 IS 1 BP 26 EP 33 DI 10.1097/MOP.0000000000000298 PG 8 WC Pediatrics SC Pediatrics GA DA4AJ UT WOS:000367742200005 PM 26626558 ER PT J AU Held, KD Woloschak, GE AF Held, Kathryn D. Woloschak, Gayle E. TI NCRP PROGRAM AREA COMMITTEE 1: BASIC CRITERIA, EPIDEMIOLOGY, RADIOBIOLOGYAND RISK SO HEALTH PHYSICS LA English DT Article DE National Council on Radiation Protection and Measurements; epidemiology; radiation biology; radiation risk AB NCRP Program Area Committee (PAC) 1 addresses fundamental issues on basic criteria, epidemiology, radiation biology, and risk with regard to radiation protection and measurements. PAC 1 has overseen the work of Scientific Committee 1-22, which produced a Commentary published in November 2014 and has four active committees working on reports or commentaries providing guidance to a number of U.S. government agencies in diverse areas, including effects of low dose and low energy radiations and space radiation. C1 [Held, Kathryn D.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Woloschak, Gayle E.] Northeastern Univ, Chicago, IL USA. RP Held, KD (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 302,55 Fruit St, Boston, MA 02114 USA. EM kheld@partners.org RI Woloschak, Gayle/A-3799-2017 OI Woloschak, Gayle/0000-0001-9209-8954 NR 12 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 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2016 VL 110 IS 2 BP 98 EP 100 DI 10.1097/HP.0000000000000402 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA DA5CC UT WOS:000367818700002 PM 26717156 ER PT J AU Brink, JA Miller, DL AF Brink, James A. Miller, Donald L. TI NCRP PROGRAM AREA COMMITTEE 4: RADIATION PROTECTION IN MEDICINE SO HEALTH PHYSICS LA English DT Article DE National Council on Radiation Protection and Measurements; fluoroscopy; radiation protection; radiation; medical AB Program Area Committee (PAC) 4 deals with issues in radiation protection in healthcare settings. NCRP Statement No. 11 was published at the end of 2014, and three active scientific committees (SC) are at workSC 4-5, SC 4-7, and SC 4-8. PAC 4 is also considering a number of topics that could be addressed by new scientific committees in the future. C1 [Brink, James A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Brink, JA (reprint author), Massachusetts Gen Hosp, 175 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM jabrink@partners.org 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 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2016 VL 110 IS 2 BP 106 EP 108 DI 10.1097/HP.0000000000000403 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA DA5CC UT WOS:000367818700005 PM 26717159 ER PT J AU Berin, MC Shreffler, WG AF Berin, M. Cecilia Shreffler, Wayne G. TI Mechanisms Underlying Induction of Tolerance to Foods SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article DE Tolerance; Treg; Foxp3; IgE; IgG4; Immunotherapy; Microbiota ID REGULATORY T-CELLS; CD103(+) DENDRITIC CELLS; PEANUT ORAL IMMUNOTHERAPY; PROMOTES ALLERGIC SENSITIZATION; PEYERS-PATCHES; AUTOIMMUNE ENCEPHALOMYELITIS; IMMUNE-RESPONSES; FOXP3 EXPRESSION; IGG ANTIBODIES; GUT MICROBIOTA AB Oral tolerance refers to a systemic immune nonresponsiyeness to antigens first encountered by the oral route, and a failure in development of this homeostatic process can result in food allergy. Clinical tolerance induced by allergen immunotherapy is associated with alterations in immune mechanisms relevant to the allergic response, including reduction of basophil reactivity, induction of IgG4, loss of effector Th2 cells, and induction of Tregs. The relative contribution of these immune changes to clinical tolerance to foods, and the duration of these immune changes after termination of immunotherapy, remains to be identified. C1 [Berin, M. Cecilia] Icahn Sch Med Mt Sinai, Immunol Inst, Pediat Allergy & Immunol Mindich Child Hlth & Dev, New York, NY 10029 USA. [Shreffler, Wayne G.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. RP Berin, MC (reprint author), Icahn Sch Med Mt Sinai, Immunol Inst, Pediat Allergy & Immunol Mindich Child Hlth & Dev, One Gustave L Levy Pl,Box 1198, New York, NY 10029 USA. EM cecilia.berin@mssm.edu FU NIDDK NIH HHS [P30 DK040561] NR 74 TC 6 Z9 7 U1 3 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 EI 1557-8607 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD FEB PY 2016 VL 36 IS 1 BP 87 EP + DI 10.1016/j.iac.2015.08.002 PG 17 WC Allergy; Immunology SC Allergy; Immunology GA DA4JR UT WOS:000367766700009 PM 26617229 ER PT J AU Shumway, DA Abu-Isa, E Soto, DE Do, TT Jagsi, R AF Shumway, Dean A. Abu-Isa, Eyad Soto, Daniel E. Thy Thy Do Jagsi, Reshma TI Depigmentation Within the Radiation Field in Patients With Vitiligo SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID BREAST-CANCER; RADIOTHERAPY; CARCINOMA; SITE C1 [Shumway, Dean A.; Abu-Isa, Eyad; Jagsi, Reshma] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Thy Thy Do] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. [Soto, Daniel E.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Jagsi, R (reprint author), Univ Michigan, Dept Radiat Oncol, UHB2C490,SPC 5010,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM rjagsi@med.umich.edu OI Jagsi, Reshma/0000-0001-6562-1228 NR 10 TC 0 Z9 0 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2016 VL 94 IS 2 BP 421 EP 422 DI 10.1016/j.ijrobp.2015.10.018 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DA0XX UT WOS:000367522000025 PM 26853347 ER PT J AU Oral, E Neils, AL Doshi, BN Fu, J Muratoglu, OK AF Oral, Ebru Neils, Andrew L. Doshi, Brinda N. Fu, Jun Muratoglu, Orhun K. TI Effects of simulated oxidation on the in vitro wear and mechanical properties of irradiated and melted highly crosslinked UHMWPE SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE joint replacement; oxidation; crosslink density; elongation-at-break; tensile strength ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; VIVO OXIDATION; PROPAGATION RESISTANCE; ACETABULAR COMPONENTS; GAMMA-STERILIZATION; FATIGUE RESISTANCE; FREE-RADICALS; VITAMIN-E AB Radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) have reduced the wear rate of the bearing surface in total joint arthroplasty and the incidence of peri-prosthetic bone loss due to wear particles. The oxidation potential afforded to the material by the trapped residual free radicals after irradiation was addressed in first generation crosslinked UHMWPEs by using thermal treatments such as annealing or melting after irradiation. Postirradiation melted crosslinked UHMWPE did not contain detectable free radicals at the time of implantation and was expected to be resistant against oxidation for the lifetime of the implants. Recent analyses of long-term retrievals showed it was possible for irradiated and melted UHMWPEs to oxidize in vivo but studies on the effects of oxidation on these materials have been limited. In this study, we determined the effects of in vitro aging on the wear and mechanical properties of irradiated and melted UHMWPE as a function of radiation dose and found that even small amount of oxidation (oxidation index of 0.1) can have detrimental effects on its mechanical properties. There was a gradual increase in the wear rate below an oxidation index of 1 and a drastic increase thereafter. Therefore, it was shown in a simulated environment that oxidation can have detrimental effects to the clinically relevant properties of irradiated and melted UHMWPEs. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 316-322, 2016. C1 [Oral, Ebru; Neils, Andrew L.; Doshi, Brinda N.; Fu, Jun; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Oral, Ebru; Fu, Jun; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Oral, E (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. EM eoral@partners.org NR 53 TC 2 Z9 3 U1 4 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4973 EI 1552-4981 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD FEB PY 2016 VL 104 IS 2 BP 316 EP 322 DI 10.1002/jbm.b.33368 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA DA5HO UT WOS:000367834100010 PM 25766106 ER PT J AU Browne, KC Wray, TB Stappenbeck, CA Krenek, M Simpson, TL AF Browne, Kendall C. Wray, Tyler B. Stappenbeck, Cynthia A. Krenek, Marketa Simpson, Tracy L. TI Alcohol Consumption, Craving, and Craving Control Efforts Assessed Daily in the Context of Readiness to Change Among Individuals with Alcohol Dependence and PTSD SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Alcohol; PTSD; Craving; Motivation to change ID POSTTRAUMATIC-STRESS-DISORDER; ECOLOGICAL MOMENTARY ASSESSMENT; COMPULSIVE DRINKING SCALE; SUBSTANCE USE; CUE-REACTIVITY; PREDICTOR; DRINKERS; VALIDITY; TRAUMA; MODEL AB Research has demonstrated the positive association between alcohol craving and alcohol use and has identified craving as a central component of alcohol use disorders (AUD). Despite potential clinical implications, few studies have examined the relationship between craving and alcohol use in individuals with AUD and common psychiatric comorbidities or explored possible moderators of the craving-alcohol use relationship. The current study used daily monitoring data to: 1) replicate previous findings detecting a positive relationship between craving and alcohol use in individuals with AUD and co-occurring posttraumatic stress disorder (PTSD) and 2) extend these findings by examining the influence of initial change motivation on the craving-use relationship and within-day associations among craving, efforts to control craving, and alcohol consumption. Participants were 84 individuals with alcohol dependence and PTSD enrolled in an intervention study. Generalized estimating equations using pre-treatment baseline daily data revealed significant main effects for craving, craving control, and motivation to change alcohol use. Daily craving was positively related to alcohol use. Greater change motivation and craving control (i.e., efforts to resist craving, avoidance of thoughts and feelings related to craving) were negatively related to alcohol use. A significant interaction was detected between baseline change motivation and daily craving indicating that the association between craving and alcohol use was significantly stronger for those with low baseline change motivation. A significant interaction was also detected between craving control and daily craving, suggesting that participants were more likely to consume alcohol when experiencing high levels of craving if they reported low levels of craving control. Findings bolster the idea that efforts to prevent or ameliorate craving are critical to treatment success for individuals with AUD and PTSD who are seeking to reduce or quit drinking. Published by Elsevier Inc. C1 [Browne, Kendall C.; Krenek, Marketa; Simpson, Tracy L.] VA Puget Sound Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98018 USA. [Wray, Tyler B.; Simpson, Tracy L.] VA Puget Sound Healthcare Syst, Seattle, WA 98018 USA. [Browne, Kendall C.; Stappenbeck, Cynthia A.; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98018 USA. RP Simpson, TL (reprint author), VA Puget Sound Healthcare Syst, 1660 S Columbian Way,CESATE-116, Seattle, WA 98018 USA. EM tracy.simpson@va.gov FU NIH/NIAAA [R21 AA17130-01, R01 AA020252-01] FX This material is the result of work supported by NIH/NIAAA awards (GRANT R21 AA17130-01; R01 AA020252-01) to Dr. Tracy Simpson and by resources from the Center of Excellence in Substance Abuse Treatment and Education (CESATE), the Mental Illness Research, Education, and Clinical Center (MIRECC), the US Department of Veterans Affairs Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, and the VA Puget Sound Health Care System, Seattle, WA. The views expressed in this article are those of the authors and do not represent the views of the Department of Veteran Affairs or the United States government. Dr. Tyler Wray is now affiliated with the Department of Behavioral and Social Sciences, Brown University, School of Public Health, 121 South Main St., Providence RI 02912. NR 58 TC 1 Z9 1 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD FEB PY 2016 VL 61 BP 34 EP 41 DI 10.1016/j.jsat.2015.09.005 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA DA4HP UT WOS:000367761200005 PM 26597623 ER PT J AU Serafini, K Shipley, L Stewart, DG AF Serafini, Kelly Shipley, Leandra Stewart, David G. TI Motivation and substance use outcomes among adolescents in a school-based intervention SO ADDICTIVE BEHAVIORS LA English DT Article DE Stages of change; Adolescence; Substance use; Alcohol; Marijuana; Motivation; Transtheoretical Model of Change ID ALCOHOL PROBLEM INDEX; ABUSE TREATMENT; TRANSTHEORETICAL MODEL; COLLEGE-STUDENTS; DRINKING; READINESS; CONSEQUENCES; SAMPLE; SCALE; STAGE AB The stages of change (Precontemplation, Contemplation, Preparation, Action, and Maintenance) have been well studied in adult populations. However, fewer studies have examined how the stages of change are related to adolescent substance use. Furthermore, there have been no studies that have examined how the stages of change relate to outcomes in a school-based intervention. To better capture adolescent motivation, we added an additional group to the Transtheoretical Model of Change, which we titled Coerced Action, to represent adolescents that made changes to their substance use despite low problem recognition (representing the internal motivation of Precontemplation and the change behaviors of the Action group). We then examined how the stages of change were related to a thorough assessment of substance use at baseline and corresponding treatment outcomes. Our sample consisted of 264 adolescents (mean age: 16.1,44.5% Caucasian, 37.5% female) who participated in an 8-week, school-based Motivational Enhancement intervention. Results indicated significant group differences across the stages of change in substance use patterns (alcohol use, negative consequences, affective dysregulation), as well as treatment outcomes (alcohol use and negative consequences). For instance, adolescents in the Action group demonstrated more negative consequences at 16 weeks follow-up than those in Precontemplation and Coerced Action, F(1, 3) = 8.23,p <.001. The Coerced Action group reported the most alcohol use at 16 weeks follow-up, although the finding was not significant when post-hoc tests were conducted. This study provides meaningful support for the assessment of motivation among adolescent substance users within school-based settings. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Serafini, Kelly] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Shipley, Leandra] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Stewart, David G.] Seattle Pacific Univ, Dept Clin Psychol, Seattle, WA 98119 USA. RP Serafini, K (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. EM kelly.serafini@yale.edu FU National Institute on Drug Abuse (NIDA) [T32DA007238-23, R03DA12974-01] FX This research was supported in part through a National Institute on Drug Abuse (NIDA) grantT32DA007238-23 (Petrakis) and R03DA12974-01 (Project READY; PI: Stewart). We wish to acknowledge Michael Toohey, Ph.D., who provided feedback on this project. We also wish to thank the participants, research staff, and colleagues who participated in the original clinical trial. NR 35 TC 4 Z9 4 U1 5 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD FEB PY 2016 VL 53 BP 74 EP 79 DI 10.1016/j.addbeh.2015.10.004 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA CZ7KR UT WOS:000367278800012 PM 26458191 ER PT J AU Hiraoka, R Cook, AJ Bivona, JM Meyer, EC Morissette, SB AF Hiraoka, Regina Cook, Andrew J. Bivona, Jenny M. Meyer, Eric C. Morissette, Sandra B. TI Acceptance and Commitment Therapy in the Treatment of Depression Related to Military Sexual Trauma in a Woman Veteran: A Case Study SO CLINICAL CASE STUDIES LA English DT Article DE acceptance and commitment therapy; military sexual trauma; depression; Veterans ID AFGHANISTAN; OUTCOMES; ANXIETY; IRAQ AB Depression is commonly reported by Veterans who have experienced military sexual trauma (MST). An increasing body of literature supports the use of Acceptance and Commitment Therapy (ACT) for the treatment of depression among civilians and military Veterans; however, additional research is needed, particularly among people exposed to trauma. This clinical case study describes the application of ACT with a 21-year-old woman Veteran who sought treatment for depression related to MST. The Veteran's depression symptoms decreased substantially over the course of therapy. Moreover, she demonstrated increased ability to attend to the present moment, tolerate feelings of uncertainty, and make decisions consistent with her chosen values. Treatment implications of these findings are discussed, with an emphasis on the unique aspects of using ACT in the treatment of MST-related depression among Veterans. C1 [Hiraoka, Regina; Cook, Andrew J.; Bivona, Jenny M.; Meyer, Eric C.; Morissette, Sandra B.] Cent Texas Vet Hlth Care Syst, Waco, TX 76711 USA. [Hiraoka, Regina; Cook, Andrew J.; Meyer, Eric C.; Morissette, Sandra B.] US Dept Vet Affairs, Washington, DC USA. [Cook, Andrew J.; Meyer, Eric C.; Morissette, Sandra B.] Texas A&M Hlth Sci Ctr, Coll Med, Bryan, TX USA. RP Hiraoka, R (reprint author), Cent Texas Vet Hlth Care Syst, 4800 Mem Dr, Waco, TX 76711 USA. EM regina.hiraoka@va.gov FU Veterans Health Administration FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Veterans Health Administration. NR 26 TC 0 Z9 0 U1 4 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-6501 EI 1552-3802 J9 CLIN CASE STUD JI Clin. Case Stud. PD FEB PY 2016 VL 15 IS 1 BP 84 EP 97 DI 10.1177/1534650115594004 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DA0FJ UT WOS:000367472400006 ER PT J AU Walker, AM Zhou, XF Ananthakrishnan, AN Weiss, LS Shen, RJ Sobel, RE Bate, A Reynolds, RF AF Walker, Alexander M. Zhou, Xiaofeng Ananthakrishnan, Ashwin N. Weiss, Lisa S. Shen, Rongjun Sobel, Rachel E. Bate, Andrew Reynolds, Robert F. TI Computer-assisted expert case definition in electronic health records SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE Health outcomes; Case definition; Electronic health records; Insurance claims data; Safety surveillance ID INFLAMMATORY-BOWEL-DISEASE; ACUTE LIVER-INJURY; NEURAL-NETWORKS; IDENTIFICATION; COMPLICATIONS; VALIDATION; DATABASES; CANCER AB Purpose: To describe how computer-assisted presentation of case data can lead experts to infer machine-implementable rules for case definition in electronic health records. As an illustration the technique has been applied to obtain a definition of acute liver dysfunction (ALD) in persons with inflammatory bowel disease (IBD). Methods: The technique consists of repeatedly sampling new batches of case candidates from an enriched pool of persons meeting presumed minimal inclusion criteria, classifying the candidates by a machine-implementable candidate rule and by a human expert, and then updating the rule so that it captures new distinctions introduced by the expert. Iteration continues until an update results in an acceptably small number of changes to form a final case definition. Results: The technique was applied to structured data and terms derived by natural language processing from text records in 29,336 adults with IBD. Over three rounds the technique led to rules with increasing predictive value, as the experts identified exceptions, and increasing sensitivity, as the experts identified missing inclusion criteria. In the final rule inclusion and exclusion terms were often keyed to an ALD onset date. When compared against clinical review in an independent test round, the derived final case definition had a sensitivity of 92% and a positive predictive value of 79%. Conclusion: An iterative technique of machine-supported expert review can yield a case definition that accommodates available data, incorporates pre-existing medical knowledge, is transparent and is open to continuous improvement. The expert updates to rules may be informative in themselves. In this limited setting, the final case definition for ALD performed better than previous, published attempts using expert definitions. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Walker, Alexander M.] WHISCON, Newton, MA 02466 USA. [Zhou, Xiaofeng; Weiss, Lisa S.; Shen, Rongjun; Sobel, Rachel E.; Bate, Andrew; Reynolds, Robert F.] Pfizer, Epidemiol Res & Dev, Worldwide Safety & Regulatory, New York, NY 10017 USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Div Gastroenterol, Boston, MA 02114 USA. RP Walker, AM (reprint author), WHISCON, 275 Grove St, Newton, MA 02466 USA. EM AlecWalker@WHISCON.com OI Walker, Alexander/0000-0001-9738-5127; Sobel, Rachel/0000-0002-4492-9562 FU Pfizer, Inc. FX This work was conducted using Pfizer, Inc., internal funds and under a research contract between Pfizer and World Health Information Science Consultants. L.W., X.Z., R.S., R.E.S., A.B. and R.R. are employees and shareholders of Pfizer, Inc. The views expressed herein are the authors' and do not necessarily represent those of Pfizer, Inc. NR 21 TC 1 Z9 1 U1 3 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 EI 1872-8243 J9 INT J MED INFORM JI Int. J. Med. Inform. PD FEB PY 2016 VL 86 BP 62 EP 70 DI 10.1016/j.ijmedinf.2015.10.005 PG 9 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA CZ8NS UT WOS:000367357000009 PM 26725697 ER PT J AU Szot, P Franklin, A Miguelez, C Wang, YQ Vidaurrazaga, I Ugedo, L Sikkema, C Wilkinson, CW Raskind, MA AF Szot, Patricia Franklin, Allyn Miguelez, Cristina Wang, Yangqing Vidaurrazaga, Igor Ugedo, Luisa Sikkema, Carl Wilkinson, Charles W. Raskind, Murray A. TI Depressive-like behavior observed with a minimal loss of locus coeruleus (LC) neurons following administration of 6-hydroxydopamine is associated with electrophysiological changes and reversed with precursors of norepinephrine SO NEUROPHARMACOLOGY LA English DT Article DE Locus coeruleus; 6-Hydroxydopamine; Forced swim test; Electrophysiology; Depression ID MILD COGNITIVE IMPAIRMENT; NORADRENERGIC NERVOUS-SYSTEM; DOPAMINE-BETA-HYDROXYLASE; WISTAR-KYOTO RATS; ALZHEIMERS-DISEASE; ANTIDEPRESSANT DRUGS; PARKINSONS-DISEASE; ANIMAL-MODEL; SENILE DEMENTIA; DEFICIENT MICE AB Depression is a common co-morbid condition most often observed in subjects with mild cognitive impairment (MCI) and during the early stages of Alzheimer's disease (AD). Dysfunction of the central noradrenergic nervous system is an important component in depression. In AD, locus coeruleus (LC) noradrenergic neurons are significantly reduced pathologically and the reduction of LC neurons is hypothesized to begin very early in the progression of the disorder; however, it is not known if dysfunction of the noradrenergic system due to early LC neuronal loss is involved in mediating depression in early AD. Therefore, the purpose of this study was to determine in an animal model if a loss of noradrenergic LC neurons results in depressive-like behavior. The LC noradrenergic neuronal population was reduced by the bilateral administration of the neurotoxin 6-hydroxydopamine (6-OHDA) directly into the LC. Forced swim test (FST) was performed three weeks after the administration of 6-OHDA (5, 10 and 14 mu g/mu l), animals administered the 5 mu g/mu l of 6-OHDA demonstrated a significant increase in immobility, indicating depressive-like behavior. This increase in immobility at the 5 mu g/mu l dose was observed with a minimal loss of LC noradrenergic neurons as compared to LC neuronal loss observed at 10 and 14 mu g/mu l dose. A significant positive correlation between the number of surviving LC neurons after 6-OHDA and FST immobile time was observed, suggesting that in animals with a minimal loss of LC neurons (or a greater number of surviving LC neurons) following 6-OHDA demonstrated depressive-like behavior. As the 6-OHDA-induced loss of LC neurons is increased, the time spent immobile is reduced. Depressive-like behavior was also observed with the 5 mu g/mu l dose of 6-OHDA with a second behavior test, sucrose consumption. FST increased immobility following 6-OHDA (5 mu g/mu l) was reversed by the administration of a single dose of L-1-3-4-dihydroxyphenylalanine (DOPA) or t-threo-3,4-dihydroxyphenylserine (DOPS) prior to behavioral assessment. Surviving LC neurons 3 weeks after 6-OHDA (5 mu g/mu l) demonstrated compensatory changes of increased firing frequency, a more irregular firing pattern, and a higher percentage of cells firing in bursts. These results indicate that depressive-like behavior in mice is observed following the administration of 6-OHDA and the loss of LC noradrenergic neurons; however, the depressive-like behavior correlates positively with the number of surviving LC neurons with 6-OHDA administration. This data suggests the depression observed in MCI subjects and in the early stages of AD may due to the hypothesized early, minimal loss of LC neurons with remaining LC neurons being more active than normal. Published by Elsevier Ltd. C1 [Szot, Patricia; Franklin, Allyn; Wang, Yangqing; Raskind, Murray A.] Vet Adm Puget Sound Hlth Care Syst, Educ & Clin Ctr, Mental Illness Res, Seattle, WA USA. [Szot, Patricia; Wilkinson, Charles W.; Raskind, Murray A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Miguelez, Cristina; Vidaurrazaga, Igor; Ugedo, Luisa] Univ Basque Country, UPV EHU, Dept Pharmacol, Leioa, Spain. [Sikkema, Carl; Wilkinson, Charles W.] Vet Adm Puget Sound Hlth Care Syst, Educ & Clin Ctr, Geriatr Res, Seattle, WA USA. [Miguelez, Cristina] Univ Basque Country, UPV EHU, Dept Pharmacol, Vitoria, Spain. RP Szot, P (reprint author), VA Puget Sound Hlth Care Syst, MIRECC, 1660 S Columbian Way, Seattle, WA 98108 USA. EM szot@uw.edu RI Ugedo, Luisa/H-4244-2015; OI Ugedo, Luisa/0000-0001-5993-0606; Miguelez, Cristina/0000-0001-6624-2932 FU Department of Veterans Affairs VISN 20 (Northwest Network) Mental Illness Research, Education, and Clinical Center (MIRECC); Geriatric Research, Education, and Clinical Center (GRECC); University of Washington Department of Psychiatry and Behavioral Science; Basque Government [UFI 11/32]; Spanish Government [FIS PI12/00613] FX This work was supported by Department of Veterans Affairs VISN 20 (Northwest Network) Mental Illness Research, Education, and Clinical Center (MIRECC; Patricia Szot, Allyn Franklin, Murray A Raskind), Geriatric Research, Education, and Clinical Center (GRECC; Carl Sikkema, Charles Wilkinson), University of Washington Department of Psychiatry and Behavioral Science (Patricia Szsot, Murray A Raskind) and grants form the Basque Government (UFI 11/32) and the Spanish Government (FIS PI12/00613) (Cristiria Miguelez, Luisa Ugedo). These institutions had no further competing financial interest in relation to the work described. The authors declare no conflict of interest. NR 62 TC 1 Z9 1 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD FEB PY 2016 VL 101 BP 76 EP 86 DI 10.1016/j.neuropharm.2015.09.003 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DA0JQ UT WOS:000367483800008 PM 26362360 ER PT J AU Bouchard, C Peacock, ZS Troulis, MJ AF Bouchard, Carl Peacock, Zachary S. Troulis, Maria J. TI Pediatric Vascular Tumors of the Head and Neck SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Hemangiomas; Vascular; Lesions; Pediatric ID GIANT-CELL GRANULOMA; JUVENILE NASOPHARYNGEAL ANGIOFIBROMA; ANEURYSMAL BONE-CYSTS; INFANTILE HEMANGIOMAS; CALCITONIN THERAPY; ANTIANGIOGENIC THERAPY; ALTERNATIVE TREATMENT; ENDOSCOPIC RESECTION; PYOGENIC GRANULOMA; CONTROLLED-TRIAL AB Oral and maxillofacial surgeons are often involved in the diagnosis and treatment of vascular neoplasms of the head and neck. An incorrect diagnosis may lead to improper or unnecessary treatment. This article reviews the diagnosis and management of vascular tumors. C1 [Bouchard, Carl] Univ Laval, Ctr Hosp Univ Quebec, Hop Enfant Jesus, Quebec City, PQ, Canada. [Peacock, Zachary S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Troulis, Maria J.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Bouchard, C (reprint author), Univ Laval, Ctr Hosp Univ Quebec, Hop Enfant Jesus, Quebec City, PQ, Canada. EM carlbchrd@gmail.com NR 60 TC 0 Z9 0 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3699 EI 1558-1365 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD FEB PY 2016 VL 28 IS 1 BP 105 EP + DI 10.1016/j.coms.2015.07.010 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CZ6KI UT WOS:000367209800011 PM 26293330 ER PT J AU Voog, JC Paulus, R Shipley, WU Smith, MR McGowan, DG Jones, CU Bahary, JP Zeitzer, KL Souhami, L Leibenhaut, MH Rotman, M Husain, SM Gore, E Raben, A Chafe, S Sandler, HM Efstathiou, JA AF Voog, Justin C. Paulus, Rebecca Shipley, William U. Smith, Matthew R. McGowan, David G. Jones, Christopher U. Bahary, Jean-Paul Zeitzer, Kenneth L. Souhami, Luis Leibenhaut, Mark H. Rotman, Marvin Husain, Siraj M. Gore, Elizabeth Raben, Adam Chafe, Susan Sandler, Howard M. Efstathiou, Jason A. TI Cardiovascular Mortality Following Short-term Androgen Deprivation in Clinically Localized Prostate Cancer: An Analysis of RTOG 94-08 SO EUROPEAN UROLOGY LA English DT Article DE Prostate cancer; Hormone therapy; Radiation therapy; Cardiovascular mortality; Androgen deprivation therapy; Survival ID PHASE-III TRIAL; RADIATION-ONCOLOGY; RANDOMIZED-TRIAL; THERAPY; RADIOTHERAPY; SUPPRESSION; RISK; MEN; DISEASE; CARCINOMA AB Background: Androgen deprivation therapy (ADT) is associated with coronary heart disease and diabetes in men with prostate cancer (PCa); however, controversy exists regarding ADT and cardiovascular mortality (CVM) with limited data for lower risk disease. Objective: We conducted a hypothesis-generating retrospective analysis to evaluate the relationship between short-course ADT and CVM in patients with clinically localized PCa enrolled in a phase III trial. Design, setting, and participants: A total of 1979 men with clinically localized (T1b-2b, prostate-specific antigen [PSA] <20 ng/ml) PCa enrolled in Radiation Therapy Oncology Group (RTOG) 94-08 from 1994 to 2001. Patients were randomized to radiation therapy (RT) with or without short-course ADT (4 mo of gonadotropin-releasing hormone (GnRH) agonist therapy and antiandrogen). Median follow-up was 9.1 yr for survivors. Outcome measurements and statistical analysis: The Cox proportional hazards model assessed overall survival. The Fine-Gray proportional hazards model assessed disease-specific survival (DSS) and CVM. Covariates included age, race, weight, baseline cardiovascular disease, baseline diabetes, baseline hypertension, Gleason score, T stage, and PSA. Results and limitations: Short-course ADT improved overall survival and DSS and was not associated with an increased risk of CVM. Overall, 191 cardiovascular-related deaths were observed. At 10 yr, 83 patients (cumulative incidence rate: 10%) receiving RT and ADT versus 95 patients (cumulative incidence rate: 11%) receiving RT alone experienced CVM. The treatment arm was not associated with increased CVM (unadjusted hazard ratio: 1.07; confidence interval, 0.81-1.42; p = 0.62). Increased CVM was not observed in patients at low risk of PCa death or at high risk of cardiac-related death. Conclusions: Data from patients enrolled in RTOG 94-08 support the hypothesis that ADT does not increase CVM risk in men with clinically localized PCa treated with short-course GnRH agonist therapy. These data support ADT use in settings with proven survival benefit. Patient summary: We investigated the controversial relationship between hormone therapy and cardiovascular mortality in men with prostate cancer (PCa) treated with radiation in a large randomized trial. Our data suggest that hormone therapy does not increase the risk of cardiovascular death in patients with clinically localized PCa and support the use of such therapy in settings with proven survival benefit. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Voog, Justin C.] Harvard Radiat Oncol Program, Boston, MA USA. [Paulus, Rebecca] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA. [Shipley, William U.; Smith, Matthew R.; Efstathiou, Jason A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [McGowan, David G.; Chafe, Susan] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Jones, Christopher U.; Leibenhaut, Mark H.] Sutter Canc Ctr, Radiol Associates Sacramento, Sacramento, CA USA. [Bahary, Jean-Paul] CHUM Hosp Norte Dame, Montreal, PQ, Canada. [Zeitzer, Kenneth L.] Albert Einstein Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19141 USA. [Souhami, Luis] McGill Univ, Montreal, PQ, Canada. [Rotman, Marvin] Brooklyn MB CCOP SUNY Downstate, Brooklyn, NY USA. [Husain, Siraj M.] Tom Baker Canc Clin, Calgary, AB, Canada. [Gore, Elizabeth] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Raben, Adam] Christiana Care Hlth Serv Inc, CCOP, Newark, DE USA. [Sandler, Howard M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Efstathiou, JA (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org FU National Cancer Institute [U10CA21661, U10CA180868, U10CA180822, U10CA37422, U24CA180803]; Prostate Cancer Foundation FX This project was supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, and U24CA180803 from the National Cancer Institute. Jason A. Efstathiou received support from the Prostate Cancer Foundation Young Investigator Award. Matthew R. Smith received support from the Prostate Cancer Foundation Challenge Award. NR 28 TC 6 Z9 6 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD FEB PY 2016 VL 69 IS 2 BP 204 EP 210 DI 10.1016/j.eururo.2015.08.027 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CZ4LK UT WOS:000367074400008 PM 26362090 ER PT J AU Voog, JC Paulus, R Efstathiou, JA AF Voog, Justin C. Paulus, Rebecca Efstathiou, Jason A. TI Reply from Authors re: Ronald C. Chen. Decisions Regarding Whether to Use Androgen Deprivation Therapy with Radiotherapy in Prostate Cancer: Is Cardiovascular Mortality the Most Relevant Outcome? Eur Urol 2016;69:211-2 Outcomes for Favorable and Unfavorable Intermediate Risk Prostate Cancer Patients Receiving Radiation Therapy With or Without Short-term Androgen Deprivation Therapy SO EUROPEAN UROLOGY LA English DT Editorial Material ID BEAM RADIATION-THERAPY; DISEASE C1 [Voog, Justin C.] Harvard Radiat Oncol Program, Boston, MA USA. [Paulus, Rebecca] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA. [Efstathiou, Jason A.] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Cox 3,100 Blossom St, Boston, MA 02114 USA. EM jefstathiou@partners.org FU NCI NIH HHS [U10 CA180868, U10 CA021661, U10 CA180822] NR 8 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD FEB PY 2016 VL 69 IS 2 BP 212 EP 213 DI 10.1016/j.eururo.2015.09.030 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA CZ4LK UT WOS:000367074400010 PM 26443430 ER PT J AU Menendez, ME Ring, D AF Menendez, Mariano E. Ring, David TI Factors Associated with Greater Pain Intensity SO HAND CLINICS LA English DT Article DE Pain intensity; Nociception; Pathophysiology; Impairment; Illness; Magnitude of disability ID MUSCULOSKELETAL PAIN; TRAPEZIOMETACARPAL JOINT; OPERATIVE TREATMENT; OPIOID USE; HEALTH; PRESCRIPTION; SATISFACTION; DEPRESSION; PREVALENCE; DISABILITY AB The intensity of pain reported for a given nociception is highly variable. Variation in pain intensity is best accounted for by stress, distress, and ineffective coping strategies. Among orthopedic surgery patients, greater intake of opioids is associated with greater pain intensity and decreased satisfaction with pain control, no matter the pathophysiology or nociception. The single most effective pain reliever is self-efficacy (the sense that one can manage and that everything will be okay). C1 [Menendez, Mariano E.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr,Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr,Dept Orthopaed Surg, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM dring@partners.org NR 30 TC 1 Z9 1 U1 1 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 0749-0712 EI 1558-1969 J9 HAND CLIN JI Hand Clin. PD FEB PY 2016 VL 32 IS 1 BP 27 EP + DI 10.1016/j.hcl.2015.08.004 PG 6 WC Orthopedics SC Orthopedics GA CZ2ST UT WOS:000366955600005 PM 26611386 ER PT J AU Chan, JA Kulke, MH AF Chan, Jennifer A. Kulke, Matthew H. TI Neuroendocrine Tumors-Current and Future Clinical Advances Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Chan, Jennifer A.; Kulke, Matthew H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chan, JA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM jang@partners.org; Matthew_Kulke@dfci.harvard.edu NR 0 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 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 2016 VL 30 IS 1 BP XIII EP XIV DI 10.1016/j.hoc.2015.09.012 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA CZ6HQ UT WOS:000367202200001 PM 26614379 ER PT J AU Demissei, BG Cleland, JG O'Connor, CM Metra, M Ponikowski, P Teerlink, JR Davison, B Givertz, MM Bloomfield, DM Dittrich, H van Veldhuisen, DJ Hillege, HL Voors, AA Cotter, G AF Demissei, Biniyam G. Cleland, John G. O'Connor, Christopher M. Metra, Marco Ponikowski, Piotr Teerlink, John R. Davison, Beth Givertz, Michael M. Bloomfield, Daniel M. Dittrich, Howard van Veldhuisen, Dirk J. Hillege, Hans L. Voors, Adriaan A. Cotter, Gad TI Procalcitonin-based indication of bacterial infection identifies high risk acute heart failure patients SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Acute heart failure; Procalcitonin; Bacterial infection; Prognosis ID C-REACTIVE PROTEIN; COMMUNITY-ACQUIRED PNEUMONIA; TERM PROGNOSIS; DIAGNOSIS; TRIAL; OUTCOMES; ADULTS; ROLOFYLLINE; ANTAGONIST; BACTEREMIA AB Background: Bacterial infections in patients hospitalized with acute heart failure are related to worse prognosis, but they can be difficult to diagnose. In this study we evaluated the prevalence, clinical correlates and association with outcomes of significantly elevated procalcitonin levels in patients hospitalized for acute heart failure without clear signs of bacterial infection. Methods: 1781 patients from the PROTECT trial were included. Patients with a body temperature >38 degrees C, sepsis or active infection requiring IV antibiotics were excluded. Significant elevation of procalcitonin was considered present when levels exceeded 0.20 ng/mL. In-hospital and post-discharge outcomes were compared between groups of patients with and without elevated procalcitonin levels. Results: Procalcitonin >= 0.20 ng/mL was seen in 6.0% of patients (N = 104). This group of patients had lower serum albumin, lower hemoglobin, higher leukocyte count, higher C-reactive protein, higher blood urea nitrogen, higher heart rate and more pulmonary rales. Interestingly, no significant differences were observed between the two groups in terms of severity of heart failure evidenced by left ventricular ejection fraction (LVEF) or B-type natriuretic peptide (BNP) levels. Patients with significantly elevated procalcitonin levels were more often classified as treatment failure or unchanged status, and had an increased risk of 30-day all-cause mortality even after adjustment for established prognosticators; HR = 2.3 (95% CI, 1.3-4.2), (P = 0.005). Conclusion: Patients with acute heart failure and significantly elevated procalcitonin levels, indicating probable undiagnosed/untreated bacterial infection, had poorer in-hospital and post-discharge outcomes, despite similar severity of heart failure. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Demissei, Biniyam G.; van Veldhuisen, Dirk J.; Hillege, Hans L.; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Demissei, Biniyam G.; Hillege, Hans L.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Cleland, John G.] Univ London Imperial Coll Sci Technol & Med, London, England. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Metra, Marco] Univ Brescia, Brescia, Italy. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Davison, Beth; Cotter, Gad] Momentum Res, Durham, NC USA. [Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bloomfield, Daniel M.] Brigham & Womens Hosp, Boston, MA USA. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Dittrich, Howard] Univ Iowa, Carver Coll Med, Abboud Cardiovasc Res Ctr, Iowa City, IA 52242 USA. RP Voors, AA (reprint author), Univ Med Ctr Groningen, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM a.a.voors@umcg.nl RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Cleland, John/0000-0002-1471-7016 FU NovaCardia FX The PROTECT trial was supported by NovaCardia, a subsidiary of Merck. Alere and Singulex kindly provided assays and performed biomarker measurements. NR 32 TC 3 Z9 3 U1 1 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD FEB 1 PY 2016 VL 204 BP 164 EP 171 DI 10.1016/j.ijcard.2015.11.141 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CZ3MM UT WOS:000367008200048 PM 26666342 ER PT J AU Lupon, J Sanders-van Wijk, S Januzzi, JL de Antonio, M Gaggin, HK Pfisterer, M Galan, A Shah, R Brunner-La Rocca, HP Bayes-Genis, A AF Lupon, Josep Sanders-van Wijk, Sandra Januzzi, James L. de Antonio, Marta Gaggin, Hanna K. Pfisterer, Matthias Galan, Amparo Shah, Ravi Brunner-La Rocca, Hans-Peter Bayes-Genis, Antoni TI Prediction of survival and magnitude of reverse remodeling using the ST2-R2 score in heart failure: A multicenter study SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Heart failure; Reverse remodeling; LVEF; Biomarkers; ST2; Survival ID CARDIAC RESYNCHRONIZATION THERAPY; DILATED CARDIOMYOPATHY; EJECTION FRACTION; BIOMARKERS; IMPROVEMENT; GALECTIN-3; MORTALITY; PROTECT AB Background: Cardiac remodeling and its reversibility are key in HF outcomes. The ST2-R2 score was recently developed to predict relevant left ventricular (LV) reverse remodeling (R2) in patients with heart failure (HF). In the present study we sought to validate the ST2-R2 score for grading improvement in LV ejection fraction (EF) and LV size at one year, and to evaluate its prognostic implication up to 4 years. Methods: A total of 569 patients with baseline LVEF <40% from three international cohorts (Barcelona, TIME-CHF, and PROTECT) were included in the study. Patients were classified into four strata based on their ST2-R2 score, which took into account concentrations of the biomarker ST2, non-ischemic etiology, absence of left bundle branch block, HF duration, baseline LVEF, and beta-blocker treatment. Results: A significant relationship was observed between ST2-R2 scores and changes in LVEF and indexed LV sizes. LVEF recovery (from + 5.6% to + 17.3%; p < 0.001), percentage reduction in LV end-systolic volume index (from - 6.1% to - 32.1%; p < 0.001) and in LV end-systolic diameter index (from - 1.1% to - 18.6%; p < 0.001) increased over the ST2-R2 strata. A similar trend was observed with diastolic parameters. Improvement in LV function and size was inversely predictive of mortality. Hazard ratios for risk of death, using the lower ST2-R2 score strata (<9) as a reference, were 0.49 (p < 0.001; score 9-11), 0.27 (p < 0.001; score 12-14), and 0.17 (p < 0.001; score 15-17). Conclusions: The ST2-R2 score predicts reverse LV remodeling in HF patients and is useful for predicting mortality up to 4 years. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Lupon, Josep; de Antonio, Marta; Bayes-Genis, Antoni] Hosp Badalona Germans Trias & Pujol, Unitat Insuficiencia Cardiaca, Barcelona 08916, Spain. [Lupon, Josep; Bayes-Genis, Antoni] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain. [Sanders-van Wijk, Sandra; Brunner-La Rocca, Hans-Peter] Maastricht Univ Med Ctr MUMC, Dept Cardiol, Maastricht, Netherlands. [Januzzi, James L.; Gaggin, Hanna K.; Shah, Ravi] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pfisterer, Matthias] Univ Basel Hosp, Basel, Switzerland. [Galan, Amparo] Hosp Badalona Germans Trias & Pujol, Serv Bioquim, Badalona, Spain. RP Bayes-Genis, A (reprint author), Hosp Badalona Germans Trias & Pujol, Serv Cardiol, Carretera Canyet S-N, Barcelona 08916, Spain. EM abayesgenis@gmail.com OI Lupon, Josep/0000-0002-5601-9611 FU Horten Research Foundation (Lugano, Switzerland); European Commission's Seventh Framework Program (FP7-HEALTH, EU-Mascara FP7 health) [278249]; European Commission's Seventh Framework Program (FP7-HEALTH HOMAGE) [305507]; AstraZeneca Pharma; Novartis Pharma; MenariniPharma; Pfizer Pharma; Servier; Roche Diagnostics; Roche Pharma; Merck Pharma FX ST2 assays in the Barcelona cohort were performed by Critical Diagnostics. The Company had no role in the design of the study or the collection, management, analysis, or interpretation of the data. TIME-CHF was supported by the Horten Research Foundation (Lugano, Switzerland; $55% of the study's budget), as well as by the European Commission's Seventh Framework Programs (FP7-HEALTH-2011, EU-Mascara FP7 health 2011 (Grant agreement no. 278249) and FP7-HEALTH-2012 HOMAGE (grant agreement no. 305507)) and several smaller unrestricted grants from AstraZeneca Pharma, Novartis Pharma, MenariniPharma, Pfizer Pharma, Servier, Roche Diagnostics, Roche Pharma, and Merck Pharma. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or in the preparation of the manuscript. NR 21 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD FEB 1 PY 2016 VL 204 BP 242 EP 247 DI 10.1016/j.ijcard.2015.11.163 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CZ3MM UT WOS:000367008200062 PM 26682955 ER PT J AU Shin, MW Bae, SJ Wee, HJ Lee, HJ Ahn, BJ Le, H Lee, EJ Kim, RH Lee, HS Seo, JH Park, JH Kim, KW AF Shin, Min Wook Bae, Sung-Jin Wee, Hee-Jun Lee, Hyo-Jong Ahn, Bum Ju Le, Hoang Lee, Eun Ji Kim, Ran Hee Lee, Hye Shin Seo, Ji Hae Park, Ji-Hyeon Kim, Kyu-Won TI Ninjurin1 regulates lipopolysaccharide-induced inflammation through direct binding SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ninjurin1; lipopolysaccharide; lipopolysaccharide binding; inflammation; macrophage ID ADHESION MOLECULE; TNF-ALPHA; MYCOPLASMA-FERMENTANS; INNATE IMMUNITY; CANCER; LPS; EXPRESSION; PROTEIN; RECOGNITION; RECEPTOR AB Ninjurin1 is a transmembrane protein involved in macrophage migration and adhesion during inflammation. It was recently reported that repression of Ninjurin1 attenuated the lipopolysaccharide (LPS)-induced inflammatory response in macrophages; however, the precise mechanism by which Ninjurin1 modulates LPS-induced inflammation remains poorly understood. In the present study, we found that the interaction between Ninjurin1 and LPS contributed to the LPS-induced inflammatory response. Notably, pull-down assays using lysates from HEK293T cells transfected with human or mouse Ninjurin1 and biotinylated LPS (LPS-biotin) showed that LPS directly bound Ninjurin1. Subsequently, LPS binding assays with various truncated forms of Ninjurin1 protein revealed that amino acids (aa) 81-100 of Ninjurin1 were required for LPS binding. In addition, knockdown experiments using Ninj1 siRNA resulted in decreased nitric oxide (NO) and tumor necrosis factor-alpha (TNF alpha) secretion upon LPS treatment in Raw264.7 cells. Collectively, our results suggest that Ninjurin1 regulates the LPS-induced inflammatory response through its direct binding to LPS, thus, identifying Ninjurin1 as a putative target for the treatment of inflammatory diseases, such as sepsis and inflammation-associated carcinogenesis. C1 [Shin, Min Wook; Bae, Sung-Jin; Wee, Hee-Jun; Ahn, Bum Ju; Le, Hoang; Lee, Eun Ji; Kim, Ran Hee; Lee, Hye Shin; Seo, Ji Hae; Park, Ji-Hyeon; Kim, Kyu-Won] Seoul Natl Univ, SNU Harvard NeuroVasc Protect Res Ctr, Coll Pharm, Seoul 151742, South Korea. [Shin, Min Wook; Bae, Sung-Jin; Wee, Hee-Jun; Ahn, Bum Ju; Le, Hoang; Lee, Eun Ji; Kim, Ran Hee; Lee, Hye Shin; Seo, Ji Hae; Park, Ji-Hyeon; Kim, Kyu-Won] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. [Lee, Hyo-Jong] Inje Univ, Coll Pharm, Gimhae 621749, Gyugnam, South Korea. [Ahn, Bum Ju] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol & Neurol, Charlestown, MA 02129 USA. [Ahn, Bum Ju] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Kim, Kyu-Won] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul 151742, South Korea. [Kim, Kyu-Won] Seoul Natl Univ, GreenBio Sci & Technol, Crop Biotechnol Inst, Pyeongchang 25354, South Korea. RP Kim, KW (reprint author), Seoul Natl Univ, SNU Harvard NeuroVasc Protect Res Ctr, Coll Pharm, Seoul 151742, South Korea. EM qwonkim@snu.ac.kr FU Global Research Laboratory Program [2011-0021874]; Global Core Research Center (GCRC) Program [2011-0030001]; International Cooperation Program [2014K2A1C2074279]; Basic Science Research Program through the National Research Foundation (NRF) - Korean Ministry of Science, ICT and Future Planning (MSIP) [2013R1A1A2058956] FX This study was supported by the Global Research Laboratory Program (2011-0021874), the Global Core Research Center (GCRC) Program (2011-0030001), the International Cooperation Program (2014K2A1C2074279), the Basic Science Research Program (2013R1A1A2058956) through the National Research Foundation (NRF) funded by the Korean Ministry of Science, ICT and Future Planning (MSIP). NR 33 TC 1 Z9 1 U1 0 U2 5 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 EI 1791-2423 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 2016 VL 48 IS 2 BP 821 EP 828 DI 10.3892/ijo.2015.3296 PG 8 WC Oncology SC Oncology GA CZ1WV UT WOS:000366897500039 PM 26677008 ER PT J AU Ali, A Tawakol, A AF Ali, Abdelrahman Tawakol, Ahmed TI FDG PET/CT Imaging of Carotid Atherosclerosis SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article DE FDG-PET; Arterial inflammation; Atherosclerosis; Stroke; CVD ID POSITRON-EMISSION-TOMOGRAPHY; PROSTHETIC VALVE ENDOCARDITIS; RANDOMIZED CLINICAL-TRIAL; ACUTE CORONARY SYNDROME; PLAQUE INFLAMMATION; ARTERIAL INFLAMMATION; F-18-FLUORODEOXYGLUCOSE UPTAKE; RHEUMATOID-ARTHRITIS; CARDIAC SARCOIDOSIS; COMPUTED-TOMOGRAPHY AB Atherosclerosis is a complex inflammatory process and an integral component of myocardial infarction and stroke. Atherosclerotic plaques can be detected using ultrasonography, myocardial perfusion imaging, coronary angiography, multidetector computed tomography (CT), and MR imaging. These modalities assess the luminal encroachment of the plaques or the structural features. Imaging plaque biology in concert with plaque structure may provide important insights. PET scanning using 18F fluorodeoxyglucose. (F-18 FDG-PET) is commonly combined with CT scanning to characterize oncological processes. This review examines the role of F-18 FDG-PET/CT imaging in the characterization of atherosclerotic plaque biology. C1 [Ali, Abdelrahman; Tawakol, Ahmed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. [Tawakol, Ahmed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@partners.org NR 55 TC 2 Z9 2 U1 2 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1052-5149 EI 1557-9867 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 2016 VL 26 IS 1 BP 45 EP + DI 10.1016/j.nic.2015.09.004 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CZ2QO UT WOS:000366949900006 PM 26610659 ER PT J AU Leeman-Markowski, BA Schachter, SC AF Leeman-Markowski, Beth A. Schachter, Steven C. TI Treatment of Cognitive Deficits in Epilepsy SO NEUROLOGIC CLINICS LA English DT Article DE Epilepsy; Seizures; Cognition; Memory; Attention; Language; Executive function; Neuropsychological ID TEMPORAL-LOBE EPILEPSY; DEEP-BRAIN-STIMULATION; VAGUS NERVE-STIMULATION; RANDOMIZED CONTROLLED-TRIAL; SEVERE ALZHEIMER-DISEASE; FOCAL INTERICTAL SPIKES; QUALITY-OF-LIFE; ATTENTION-DEFICIT; HYPERACTIVITY DISORDER; VERBAL MEMORY AB Cognitive deficits, including attention, language, memory, and executive dysfunction, are common in the setting of epilepsy and can greatly impair quality of life. The etiology is often multifactorial and may be due to the underlying seizure disorder, adverse effects of treatment, and psychiatric comorbidities, among other factors. Management of cognitive deficits aims to address these underlying etiologies as well as provide rehabilitative strategies. Several investigational therapies are also currently under study. This article examines current and future treatments for cognitive dysfunction in epilepsy. C1 [Leeman-Markowski, Beth A.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Schachter, Steven C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Massachusetts Gen Hosp,CIMIT, Boston, MA 02114 USA. RP Leeman-Markowski, BA (reprint author), Emory Univ, Dept Neurol, 101 Woodruff Circle,Suite 6000, Atlanta, GA 30322 USA. EM beth.a.leeman@emory.edu NR 157 TC 1 Z9 1 U1 3 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8619 EI 1557-9875 J9 NEUROL CLIN JI Neurol. Clin. PD FEB PY 2016 VL 34 IS 1 BP 183 EP + DI 10.1016/j.ncl.2015.08.008 PG 23 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CZ6HD UT WOS:000367200900009 PM 26613999 ER PT J AU Sumner, JA Duncan, L Ratanatharathorn, A Roberts, AL Koenen, KC AF Sumner, J. A. Duncan, L. Ratanatharathorn, A. Roberts, A. L. Koenen, K. C. TI Research Letter: PTSD has shared polygenic contributions with bipolar disorder and schizophrenia in women SO PSYCHOLOGICAL MEDICINE LA English DT Letter ID POSTTRAUMATIC-STRESS-DISORDER; VULNERABILITY; ASSOCIATION C1 [Sumner, J. A.] Columbia Univ, Med Ctr, Ctr Behav Cardiovasc Hlth, New York, NY 10032 USA. [Sumner, J. A.; Ratanatharathorn, A.; Koenen, K. C.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA USA. [Duncan, L.; Koenen, K. C.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, stactr, Cambridge, MA USA. [Duncan, L.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Duncan, L.] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA USA. [Ratanatharathorn, A.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Roberts, A. L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Koenen, K. C.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Koenen, K. C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Sumner, JA (reprint author), Columbia Univ, Med Ctr, Ctr Behav Cardiovasc Hlth, 622 W 168th St,PH 9-315, New York, NY 10032 USA. EM js4456@cumc.columbia.edu FU National Institutes of Health [R01 MH078828, U01 MH094421, UM1 CA176726] FX This study was supported by the National Institutes of Health grants R01 MH078828 (to Dr. Koenen), U01 MH094421 (for development of the Psych Chip), and UM1 CA176726 (for NHS II infrastructure). We acknowledge the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School for managing the NHS II. NR 6 TC 0 Z9 0 U1 2 U2 3 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 FEB PY 2016 VL 46 IS 3 BP 669 EP 671 DI 10.1017/S0033291715002135 PG 3 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CZ5WG UT WOS:000367172500020 PM 26464113 ER PT J AU Bolster, MB AF Bolster, Marcy B. TI Corticosteroids: Friends and Foes Preface SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Bolster, Marcy B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Rheumatol Fellowship Training Program, Boston, MA 02114 USA. RP Bolster, MB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Rheumatol Fellowship Training Program, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. EM mbolster@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-857X EI 1558-3163 J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 2016 VL 42 IS 1 BP XV EP XVI DI 10.1016/j.rdc.2015.10.001 PG 2 WC Rheumatology SC Rheumatology GA CZ1RB UT WOS:000366881900002 PM 26611560 ER PT J AU Keller, SF Miloslavsky, EM AF Keller, Sarah F. Miloslavsky, Eli M. TI Corticosteroids in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Glucocorticoids; ANCA-associated vasculitis; Granulomatosis with polyangiitis; Microscopic polyangiitis ID ANCA-ASSOCIATED VASCULITIS; WEGENERS-GRANULOMATOSIS; RANDOMIZED-TRIAL; GLUCOCORTICOID THERAPY; RHEUMATOID-ARTHRITIS; SUBGLOTTIC STENOSIS; MAINTENANCE THERAPY; MYCOPHENOLATE-MOFETIL; REMISSION MAINTENANCE; RENAL VASCULITIS AB Glucocorticoids (GCs) have been the cornerstone of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) therapy since their advent in the 1950s. There is considerable variation in their use, both with respect to dose and duration. Given considerable treatment-related morbidity and mortality, refining the role of GCs is becoming increasingly important. This article discusses the current role of GCs in various phases of AAV treatment, including remission induction, maintenance therapy, treatment of relapses, and the use of local GCs. It discusses current controversies relating to GC use as well as research efforts that seek to reduce GC toxicity in AAV. C1 [Keller, Sarah F.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Miloslavsky, Eli M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol,Dept Med,Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. RP Miloslavsky, EM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol,Dept Med,Yawkey Ctr Outpatient Care, Suite 2C, Boston, MA 02114 USA. EM emiloslavsky@mgh.harvard.edu FU Genentech [224513] FX Dr S.F. Keller has nothing to disclose. Dr E.M. Miloslavsky has received research support from Genentech (#224513). NR 60 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 0889-857X EI 1558-3163 J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 2016 VL 42 IS 1 BP 91 EP + DI 10.1016/j.rdc.2015.08.010 PG 12 WC Rheumatology SC Rheumatology GA CZ1RB UT WOS:000366881900009 PM 26611553 ER PT J AU Simeone, FJ Bennett, DL Chang, CY Huang, AJ Kattapuram, SV Bredella, MA Torriani, M AF Simeone, F. Joseph Bennett, Debbie L. Chang, Connie Y. Huang, Ambrose J. Kattapuram, Susan V. Bredella, Miriam A. Torriani, Martin TI Retrospective analysis of intravertebral collateral enhancement in patients with central venous obstruction SO SKELETAL RADIOLOGY LA English DT Article DE Intravertebral collateral enhancement; Central venous obstruction; Vena cava obstruction; Collateral venous pathways ID VENA-CAVA OBSTRUCTION; VERTEBRAL BODY ENHANCEMENT; BONE-LESIONS; SUPERIOR; CT AB To compare prevalence and patterns of intravertebral collateral enhancement in patients with and without central venous obstruction (CVO). Chest CTs performed between 1/1/2000 and 12/15/2012 with reports containing terms indicating CVO were identified. All contrast enhanced CTs were examined for the presence of CVO and collateral venous pathways. If intravertebral collateral enhancement was present, the pattern was recorded as nodular, linear, or both. In 209 suspected cases of CVO, 53 (25 %) were confirmed with obstruction and 156 (75 %) were without obstruction. In patients with CVO, 47 % (25/53) demonstrated collateral venous flow through an intravertebral marrow pathway compared to 5 % (8/156) of patients without CVO (P < 0.0001). The most common level of enhancement was the upper thoracic spine, involving only the vertebral body. Nodular, linear, and combined nodular-linear enhancement patterns were seen with similar frequency. Nodular intravertebral collateral enhancement was mistaken for sclerotic metastases in 33 % (3/9) of cases. Intravertebral collateral enhancement was seen in almost half the patients with CVO and when nodular enhancement is present, it is important to differentiate between metastatic lesions and enhancement related to CVO. C1 [Simeone, F. Joseph; Chang, Connie Y.; Huang, Ambrose J.; Kattapuram, Susan V.; Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Simeone, F. Joseph; Chang, Connie Y.; Huang, Ambrose J.; Kattapuram, Susan V.; Bredella, Miriam A.; Torriani, Martin] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bennett, Debbie L.] St Louis Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. RP Simeone, FJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St YAW 6033, Boston, MA 02114 USA. EM FSIMEONE@PARTNERS.ORG; bennettdl@slu.edu; cychang@mgh.harvard.edu; ajhuang@mgh.harvard.edu; skattapuram@mgh.harvard.edu; mbredella@mgh.harvard.edu; mtorriani@mgh.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD FEB PY 2016 VL 45 IS 2 BP 163 EP 168 DI 10.1007/s00256-015-2274-6 PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CZ3LA UT WOS:000367004400002 PM 26497542 ER PT J AU Singhal, V Miller, KK Torriani, M Bredella, MA AF Singhal, Vibha Miller, Karen K. Torriani, Martin Bredella, Miriam A. TI Short- and long-term reproducibility of marrow adipose tissue quantification by 1H-MR spectroscopy SO SKELETAL RADIOLOGY LA English DT Article DE Proton MR spectroscopy; Marrow adipose tissue; Reproducibility ID PROTON MR SPECTROSCOPY; BONE-MINERAL DENSITY; BODY-COMPOSITION; FAT-CONTENT; ANOREXIA-NERVOSA; WOMEN; OSTEOPOROSIS; MICROARCHITECTURE; DISEASE; OBESITY AB To assess short- and long-term reproducibility of marrow adipose tissue (MAT) quantification by 1H-MR spectroscopy. Our study was IRB-approved and HIPAA compliant. Written informed consent was obtained. We studied 20 overweight/obese but otherwise healthy subjects (12 female, 8 male) with a mean age of 37 +/- 6 years. All subjects underwent proton magnetic resonance spectroscopy (1H-MRS) of the fourth lumbar vertebral body using a single-voxel point-resolved spatially localized spectroscopy sequence without water suppression at 3 T. Measurements were repeated after 6 weeks and 6 months using identical scanning protocols. The following clinical parameters were collected, weight, BMI, exercise status, and trabecular bone mineral density (BMD), by quantitative computed tomography. Short- (baseline, 6 weeks) and long-term (baseline, 6 months) reproducibility of MAT was assessed by the coefficient of variance (CV), standard deviation (SD), and interclass correlation coefficients (ICCs). Short- and long-term changes in clinical parameters were assessed by paired t-test. For short-term reproducibility between baseline and 6-week scans, the CV was 9.9 %, SD was 0.08, and ICC was 0.97 (95 % CI 0.94-099). For long-term reproducibility between baseline and 6-month scans, the CV was 12.0 %, SD was 0.10, and ICC was 0.95 (95 % CI 0.88 to 0.98). There was no significant short- or long-term change in clinical parameters (weight, BMI, exercise status, BMD) (p > 0.2). 1H-MRS is a reproducible method for short- and long-term quantification of MAT. Our results can guide sample size calculations for interventional and longitudinal studies. C1 [Singhal, Vibha] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA USA. [Singhal, Vibha; Miller, Karen K.; Torriani, Martin; Bredella, Miriam A.] Harvard Univ, Sch Med, Boston, MA USA. [Singhal, Vibha; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA. [Torriani, Martin; Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02144 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02144 USA. EM mbredella@mgh.harvard.edu FU National Institutes of Health [R01 HL-077674, UL1 RR 025758, K23 RR-23090] FX This research was supported by the National Institutes of Health grants R01 HL-077674, UL1 RR 025758, and K23 RR-23090. NR 27 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD FEB PY 2016 VL 45 IS 2 BP 221 EP 225 DI 10.1007/s00256-015-2292-4 PG 5 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CZ3LA UT WOS:000367004400009 PM 26563561 ER PT J AU Chang, CY Simeone, FJ Huang, AJ AF Chang, Connie Y. Simeone, F. Joseph Huang, Ambrose J. TI battery powered bone drill: caution needed in densely blastic lesions Response SO SKELETAL RADIOLOGY LA English DT Letter C1 [Chang, Connie Y.] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. [Simeone, F. Joseph; Huang, Ambrose J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Chang, CY (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. EM cychang@mgh.harvard.edu; fsimeone@mgh.harvard.edu; ajhuang@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD FEB PY 2016 VL 45 IS 2 BP 283 EP 283 DI 10.1007/s00256-015-2304-4 PG 1 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CZ3LA UT WOS:000367004400018 PM 26608799 ER PT J AU Servais, E Swanson, SJ AF Servais, Elliot Swanson, Scott J. TI Thoracoscopic Management of Pulmonary Metastases SO THORACIC SURGERY CLINICS LA English DT Article DE VATS metastasectomy; Thoracoscopic surgery; Pulmonary metastasectomy; Minimally invasive surgery ID LYMPH-NODE DISSECTION; VATS LOBECTOMY; LUNG-CANCER; SURGERY; RESECTION; THORACOTOMY; PALPATION; NODULES; CHEST AB In appropriately selected patients, resection of pulmonary metastases from various primary tumors can lead to improved survival. Metastasectomy has traditionally been performed by open thoracotomy; however, thoracoscopic resection offers the important benefits of a less invasive approach with more expeditious recovery. Concerns regarding missed lesions during thoracoscopy have not been realized in analyses of survival and may be offset by a policy of repeat metastasectomy for pulmonary recurrences. Despite the relative paucity of prospective trials, the preponderance of data supports the use of video-assisted thoracic surgery for pulmonary nnetastasectomy, which represents our preferred strategy for these patients. C1 [Servais, Elliot] Harvard Univ, Cardiothorac Surg, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Swanson, Scott J.] Harvard Univ, Minimally Invas Thorac Surg, Brigham & Womens Hosp, Dana Farber Canc Inst,Canc Affairs,Dept Surg,Med, Boston, MA 02115 USA. RP Swanson, SJ (reprint author), Harvard Univ, Minimally Invas Thorac Surg, Brigham & Womens Hosp, Dana Farber Canc Inst,Canc Affairs,Dept Surg,Med, 75 Francis St, Boston, MA 02115 USA. EM sjswanson@partners.org NR 35 TC 2 Z9 2 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1547-4127 J9 THORAC SURG CLIN JI Thorac. Surg. Clin. PD FEB PY 2016 VL 26 IS 1 BP 91 EP + DI 10.1016/j.thorsurg.2015.09.011 PG 8 WC Respiratory System; Surgery SC Respiratory System; Surgery GA CZ6KJ UT WOS:000367209900012 PM 26611514 ER PT J AU Lucia, U Ponzetto, A Deisboeck, TS AF Lucia, Umberto Ponzetto, Antonio Deisboeck, Thomas S. TI Investigating the impact of electromagnetic fields on human cells: A thermodynamic perspective SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE Electromagnetic waves; Entropy generation; Magnetic resonance imaging; MRI; Thermodynamic approach to biomedicine ID YEAST-CELLS; ENTROPY GENERATION; MAGNETIC-FIELD; GLIOMA-CELLS; MEMBRANE; SYSTEMS; GROWTH AB The consequences of the interactions of electromagnetic waves, as used in conventional MRI technology, with human cells are not fully understood. To analyze these interactions, a novel thermodynamic approach is presented that is based on the relationship between electromagnetic and thermodynamic quantities. The theoretical results indicate that the waves' impact is largest at high magnetic field strengths and at low frequencies. This is the first step towards a clinically useful framework to quantitatively assess MRI impact including a potential trade-off between the desired increase in spatial resolution that higher magnetic field strengths yield for diagnostic purposes and the danger this may pose for cell membranes, and by extension, for the tissues investigated. (C) 2015 Elsevier B.V. All rights reserved. C1 [Lucia, Umberto] Politecn Torino, Dipartimento Energia, I-10129 Turin, Italy. [Ponzetto, Antonio] Univ Turin, Dept Med Sci, I-10126 Turin, Italy. [Deisboeck, Thomas S.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Deisboeck, Thomas S.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Deisboeck, Thomas S.] ThinkMotu LLC, Wellesley, MA 02481 USA. RP Lucia, U (reprint author), Politecn Torino, Dipartimento Energia, Corso Duca Abruzzi 24, I-10129 Turin, Italy. EM umberto.lucia@polito.it; antonio.ponzetto@unito.it; deisboec@helix.mgh.harvard.edu OI Lucia, Umberto/0000-0002-3123-2133; ponzetto, antonio/0000-0002-1551-3664 FU EU [265772] FX AP was supported by EU grant 'EM-safety and Hazard mitigation by proper EV design' (Project No. 265772). NR 38 TC 4 Z9 4 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 EI 1873-2119 J9 PHYSICA A JI Physica A PD FEB 1 PY 2016 VL 443 BP 42 EP 48 DI 10.1016/j.physa.2015.09.074 PG 7 WC Physics, Multidisciplinary SC Physics GA CW5QX UT WOS:000365052700005 ER PT J AU Bergman, AA Jaynes, HA Gonzalvo, JD Hudmon, KS Frankel, RM Kobylinski, AL Zillich, AJ AF Bergman, Alicia A. Jaynes, Heather A. Gonzalvo, Jasmine D. Hudmon, Karen Suchanek Frankel, Richard M. Kobylinski, Amanda L. Zillich, Alan J. TI Pharmaceutical Role Expansion and Developments in Pharmacist-Physician Communication SO HEALTH COMMUNICATION LA English DT Article ID MEDICAL HOME; PRIMARY-CARE; ORDER ENTRY; COLLABORATION; MANAGEMENT; COMPETENCES; AVIATION; TEAMS; FACE AB Expanded clinical pharmacist professional roles in the team-based patient-centered medical home (PCMH) primary care environment require cooperative and collaborative relationships among pharmacists and primary care physicians (PCPs), but many PCPs have not previously worked in such a direct fashion with pharmacists. Additional roles, including formulary control, add further elements of complexity to the clinical pharmacist-PCP relationship that are not well described. Our objective was to characterize the nature of clinical pharmacist-PCP interprofessional collaboration across seven federally funded hospitals and associated primary care clinics, following pharmacist placement in primary care clinics and incorporation of expanded pharmacist roles. In-depth and semistructured interviews were conducted with 25 practicing clinical pharmacists and 17 PCPs. Qualitative thematic analysis revealed three major themes: (1) the complexities of electronic communication (particularly electronic nonformulary requests) as contributing to interprofessional tensions or misunderstandings for both groups, (2) the navigation of new roles and traditional hierarchy, with pharmacists using indirect communication to prevent PCP defensiveness to recommendations, and (3) a preference for onsite colocation for enhanced communication and professional relationships. Clinical pharmacists' indirect communication practices may hold important implications for patient safety in the context of medication use, and it is important to foster effective communication skills and an environment where all team members across hierarchies can feel comfortable speaking up to reduce error when problems are suspected. Also, the lack of institutional communication about managing drug formulary issues and related electronic nonformulary request processes was apparent in this study and merits further attention for both researchers and practitioners. C1 [Bergman, Alicia A.; Frankel, Richard M.; Kobylinski, Amanda L.; Zillich, Alan J.] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. [Jaynes, Heather A.; Gonzalvo, Jasmine D.; Hudmon, Karen Suchanek] Purdue Univ, Coll Pharm, W Lafayette, IN 47907 USA. RP Bergman, AA (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Innovat Implementat & Policy, 16111 Plummer St,Bldg 25, North Hills, CA 91343 USA. EM Alicia.Bergman@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development [PI: Zillich-CDA RCD06304-1]; Department of Veterans Affairs, Veterans Health Administration Health Services Research and Development (HSR&D) Associated Health Fellowship Program (Bergman); Purdue/Lilly Foundation grant FX The project reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (PI: Zillich-CDA RCD06304-1), the Department of Veterans Affairs, Veterans Health Administration Health Services Research and Development (HSR&D) Associated Health Fellowship Program (Bergman), and partially supported by a Purdue/Lilly Foundation grant. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the U.S. government. NR 45 TC 0 Z9 0 U1 4 U2 34 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1041-0236 EI 1532-7027 J9 HEALTH COMMUN JI Health Commun. PD FEB 1 PY 2016 VL 31 IS 2 BP 161 EP 170 DI 10.1080/10410236.2014.940672 PG 10 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA CU7WD UT WOS:000363751600003 PM 26266465 ER PT J AU Chebl, RB Madden, B Belsky, J Harmouche, E Yessayan, L AF Chebl, Ralphe Bou Madden, Bryan Belsky, Justin Harmouche, Elie Yessayan, Lenar TI Diagnostic value of end tidal capnography in patients with hyperglycemia in the emergency department SO BMC EMERGENCY MEDICINE LA English DT Article DE Capnography; Diabetic ketoacidosis; Emergency department ID DIABETIC-KETOACIDOSIS; BETA-HYDROXYBUTYRATE; ARTERIAL; PH AB Background: Diabetic Ketoacidosis (DKA) is a potentially life-threatening emergency that requires prompt diagnosis and treatment. In paediatric populations an end tidal capnography value greater than 36 mmHg was found to be 100 % sensitive in ruling out DKA. Methods: A cross sectional observational study of adults >= 17 years of age presenting to the emergency department between January 2014 and May 2014 with glucose > 550 mg/dL. In all patients, nasal capnography and venous blood gas analysis were performed prior to any insulin or intravenous fluid administration. The diagnosis of DKA was based on the presence of anion gap metabolic acidosis, hyperglycaemia and ketonemia. The overall diagnostic performance (area under the curve [AUC]), sensitivity, specificity and likelihood ratios at different end tidal CO2 (ETCO2) cut-offs were determined. Results: 71 patients were enrolled in the study of which 21 (30 %) met the diagnosis of DKA. The area under the curve for ETCO2 was 0.95 with a 95 % CI of 0.91 to 0.99. Test sensitivity for DKA at ETCO2 level >= 35 mmHg was 100 % (95 % CI, 83.9-100). An ETCO2 level >= 21 mmHg was 100 % specific (95 % CI, 92.9-100.0) for DKA. Conclusion: Nasal capnography exhibits favourable diagnostic performance in detecting patients with or without DKA among those who present to the emergency department with a glucometer reading > 550 mg/dL. C1 [Chebl, Ralphe Bou] Amer Univ Beirut, Dept Emergency Med, Beirut, Lebanon. [Chebl, Ralphe Bou; Madden, Bryan; Harmouche, Elie] Henry Ford Hosp, Dept Emergency Med, Detroit, MI 48202 USA. [Belsky, Justin] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Yessayan, Lenar] Henry Ford Hosp, Div Nephrol & Hypertens, Detroit, MI 48202 USA. [Yessayan, Lenar] Henry Ford Hosp, Div Pulm & Crit Care Med, Detroit, MI 48202 USA. RP Chebl, RB (reprint author), Amer Univ Beirut, Dept Emergency Med, Beirut, Lebanon.; Chebl, RB (reprint author), Henry Ford Hosp, Dept Emergency Med, Detroit, MI 48202 USA. EM rb94@aub.edu.lb NR 15 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-227X J9 BMC EMERG MED JI BMC Emerg. Med. PD JAN 29 PY 2016 VL 16 AR 7 DI 10.1186/s12873-016-0072-7 PG 7 WC Emergency Medicine SC Emergency Medicine GA DO9QI UT WOS:000378121200001 ER PT J AU Russo, SG Nickel, EA Leissner, KB Schwerdtfeger, K Bauer, M Roessler, MS AF Russo, Sebastian G. Nickel, Eike A. Leissner, Kay B. Schwerdtfeger, Katrin Bauer, Martin Roessler, Markus S. TI Use of the GlideScope (R)-Ranger for pre-hospital intubations by anaesthesia trained emergency physicians - an observational study SO BMC EMERGENCY MEDICINE LA English DT Article DE Airway management; Pre-hospital; Videolaryngoscopy; GlideScope; Intubating laryngeal mask airway ID AIRWAY MANAGEMENT; VIDEO-LARYNGOSCOPY; ENDOTRACHEAL INTUBATION; DIFFICULT AIRWAY; LARYNGEAL MASK; VIDEOLARYNGOSCOPE; MULTICENTER; AMBULANCE; SUCCESS; SERVICE AB Background: Pre-hospital endotracheal intubation is more difficult than in the operating room (OR). Therefore, enhanced airway management devices such as video laryngoscopes may be helpful to improve the success rate of pre-hospital intubation. We describe the use of the Glidescope(R)-Ranger (GS-R) as an alternative airway tool used at the discretion of the emergency physician (EP) in charge. Methods: During a 3.5 year period, the GS-R was available to be used either as the primary or backup tool for pre-hospital intubation by anaesthesia trained EP with limited expertise using angulated videolaryngoscopes. Results: During this period 672 patients needed pre-hospital intubation of which the GS-R was used in 56 cases. The overall GS-R success rate was 66 % (range of 34-100 % among EP). The reasons for difficulties or failure included inexperience of the EP with the GS-R, impaired view due to secretion, vomitus, blood or the inability to see the screen in very bright environment due to sunlight. Conclusion: Special expertise and substantial training is needed to successfully accomplish tracheal intubation with the GS-R in the pre-hospital setting. Providers inexperienced with DL as well as video-assisted intubation should not expect to be able to perform tracheal intubation easily just because a videolaryngoscope is available. Additionally, indirect laryngoscopy might be difficult or even impossible to achieve in the pre-hospital setting due to impeding circumstances such as blood, secretions or bright sun-light. Therefore, videolaryngoscopes, here the GS-R, should not be considered as the "Holy Grail" of endotracheal intubation, neither for the experts nor for inexperienced providers. C1 [Russo, Sebastian G.; Nickel, Eike A.; Schwerdtfeger, Katrin; Bauer, Martin; Roessler, Markus S.] Univ Hosp Gottingen, Dept Anaesthesiol, D-370799 Gottingen, Germany. [Nickel, Eike A.] HELIOS Klinikum Emil von Behring, Dept Anaesthesiol & Pain Med, Berlin, Germany. [Leissner, Kay B.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Anesthesiol, Boston, MA USA. RP Russo, SG (reprint author), Univ Hosp Gottingen, Dept Anaesthesiol, D-370799 Gottingen, Germany. EM s.russo@medizin.uni-goettingen.de NR 22 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-227X J9 BMC EMERG MED JI BMC Emerg. Med. PD JAN 29 PY 2016 VL 16 AR 8 DI 10.1186/s12873-016-0069-2 PG 7 WC Emergency Medicine SC Emergency Medicine GA DO9QI UT WOS:000378121200002 PM 26830474 ER PT J AU Grilli, MD Verfaellie, M AF Grilli, Matthew D. Verfaellie, Mieke TI Experience-near but not experience-far autobiographical facts depend on the medial temporal lobe for retrieval: Evidence from amnesia SO NEUROPSYCHOLOGIA LA English DT Article DE Personal semantics; Autobiographical memory; Self; Semantic memory; Episodic memory ID EPISODIC FUTURE THINKING; SEMANTIC MEMORY; RELATIONAL MEMORY; DAMAGE; SELF; RECALL AB This paper addresses the idea that there may be two types of autobiographical facts with distinct cognitive and neural mechanisms: "Experience-near" autobiographical facts, which contain spatiotemporal content derived from personal experience and thus depend on the medial temporal lobe (MTL) for retrieval, and "experience-far" autobiographical facts, which are abstract memories and thus rely on neocortical brain regions involved in retrieval of general semantic memory. To investigate this conceptual model of autobiographical fact knowledge, we analyzed the nature of autobiographical facts that were generated by 8 individuals with MTL amnesia and 12 control participants in a recent study of identity and memory [Grilli, M.D., & Verfaellie, M. (2015). Supporting the self-concept with memory: insight from amnesia. Social Cognitive and Affective Neuroscience, 10, 1684-1692]. Results revealed that MTL amnesic participants generated fewer experience-near autobiographical facts than controls. Experience-far autobiographical fact generation was not impaired in amnesic participants with damage restricted to the MTL, but there was preliminary evidence to suggest that it may be impaired in amnesic participants with damage to the MTL and anterior lateral temporal lobe. These results support a cognitive and neural distinction between experience-near and experience-far autobiographical facts and have implications for understanding the contribution of autobiographical fact knowledge to self-related cognition. Published by Elsevier Ltd. C1 [Grilli, Matthew D.; Verfaellie, Mieke] Boston Univ, Sch Med, VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02118 USA. RP Verfaellie, M (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 151A, Boston, MA 02130 USA. EM verf@bu.edu FU Clinical Science Research and Development Service, Department of Veterans Affairs [IO1CX000925] FX This work was supported by: Clinical Science Research and Development Service, Department of Veterans Affairs Grant IO1CX000925. NR 31 TC 3 Z9 3 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN 29 PY 2016 VL 81 BP 180 EP 185 DI 10.1016/j.neuropsychologia.2015.12.023 PG 6 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA DE2LS UT WOS:000370459400016 PM 26721761 ER PT J AU Lucia, U Ponzetto, A Deisboeck, TS AF Lucia, Umberto Ponzetto, Antonio Deisboeck, Thomas S. TI Constructal approach to cell membranes transport: Amending the 'Norton-Simon' hypothesis for cancer treatment SO SCIENTIFIC REPORTS LA English DT Article ID HIGH LACTATE LEVELS; ENTROPY GENERATION; TUMOR-GROWTH; IN-VIVO; MULTICELLULAR TUMOR; CALCIUM-CHANNELS; TISSUE MECHANICS; VOLTAGE; MODEL; METASTASES AB To investigate biosystems, we propose a new thermodynamic concept that analyses ion, mass and energy flows across the cell membrane. This paradigm-shifting approach has a wide applicability to medically relevant topics including advancing cancer treatment. To support this claim, we revisit 'Norton-Simon' and evolving it from an already important anti-cancer hypothesis to a thermodynamic theorem in medicine. We confirm that an increase in proliferation and a reduction in apoptosis trigger a maximum of ATP consumption by the tumor cell. Moreover, we find that positive, membrane-crossing ions lead to a decrease in the energy used by the tumor, supporting the notion of their growth inhibitory effect while negative ions apparently increase the cancer's consumption of energy hence reflecting a growth promoting impact. Our results not only represent a thermodynamic proof of the original Norton-Simon hypothesis but, more concretely, they also advance the clinically intriguing and experimentally testable, diagnostic hypothesis that observing an increase in negative ions inside a cell in vitro, and inside a diseased tissue in vivo, may indicate growth or recurrence of a tumor. We conclude with providing theoretical evidence that applying electromagnetic field therapy early on in the treatment cycle may maximize its anti-cancer efficacy. C1 [Lucia, Umberto] Politecn Torino, Dipartimento Energia, Corso Duca degli Abruzzi 24, I-10129 Turin, Italy. [Ponzetto, Antonio] Univ Turin, Dept Med Sci, Corso AM Dogliotti 14, I-10126 Turin, Italy. [Deisboeck, Thomas S.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Deisboeck, Thomas S.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Deisboeck, Thomas S.] ThinkMotu LLC, Wellesley, MA 02481 USA. RP Lucia, U (reprint author), Politecn Torino, Dipartimento Energia, Corso Duca degli Abruzzi 24, I-10129 Turin, Italy. EM umberto.lucia@polito.it FU Harvard-MIT (HST) Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital, Harvard Medical School FX This study has been supported in part by the Harvard-MIT (HST) Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital, Harvard Medical School (T.S.D.). NR 72 TC 2 Z9 2 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 29 PY 2016 VL 6 AR 19451 DI 10.1038/srep19451 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC0RL UT WOS:000368925300001 PM 26822208 ER PT J AU Kaufman, CK Mosimann, C Fan, ZP Yang, S Thomas, AJ Ablain, J Tan, JL Fogley, RD van Rooijen, E Hagedorn, EJ Ciarlo, C White, RM Matos, DA Puller, AC Santoriello, C Liao, EC Young, RA Zon, LI AF Kaufman, Charles K. Mosimann, Christian Fan, Zi Peng Yang, Song Thomas, Andrew J. Ablain, Julien Tan, Justin L. Fogley, Rachel D. van Rooijen, Ellen Hagedorn, Elliott J. Ciarlo, Christie White, Richard M. Matos, Dominick A. Puller, Ann-Christin Santoriello, Cristina Liao, Eric C. Young, Richard A. Zon, Leonard I. TI A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation SO SCIENCE LA English DT Article ID SUPER-ENHANCERS; TRANSCRIPTION FACTOR; INHIBITORY-ACTIVITY; CELL IDENTITY; GENE; EXPRESSION; SOX10; CHROMATIN; DISEASE; SYSTEM AB The "cancerized field" concept posits that cancer-prone cells in a given tissue share an oncogenic mutation, but only discreet clones within the field initiate tumors. Most benign nevi carry oncogenic BRAF(V600E) mutations but rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors (NCPs) and specifically reexpressed in melanoma. Live imaging of transgenic zebrafish crestin reporters shows that within a cancerized field (BRAF(V600E)-mutant; p53-deficient), a single melanocyte reactivates the NCP state, revealing a fate change at melanoma initiation in this model. NCP transcription factors, including sox10, regulate crestin expression. Forced sox10 overexpression in melanocytes accelerated melanoma formation, which is consistent with activation of NCP genes and super-enhancers leading to melanoma. Our work highlights NCP state reemergence as a key event in melanoma initiation. C1 [Kaufman, Charles K.; Yang, Song; Thomas, Andrew J.; Ablain, Julien; Tan, Justin L.; Fogley, Rachel D.; van Rooijen, Ellen; Hagedorn, Elliott J.; Ciarlo, Christie; Santoriello, Cristina; Zon, Leonard I.] Childrens Hosp Boston, Howard Hughes Med Inst, Stem Cell Program, Boston, MA 02115 USA. [Kaufman, Charles K.; Yang, Song; Thomas, Andrew J.; Ablain, Julien; Tan, Justin L.; Fogley, Rachel D.; van Rooijen, Ellen; Hagedorn, Elliott J.; Ciarlo, Christie; Santoriello, Cristina; Zon, Leonard I.] Childrens Hosp Boston, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Kaufman, Charles K.; Yang, Song; Ablain, Julien; van Rooijen, Ellen; Hagedorn, Elliott J.; Liao, Eric C.; Zon, Leonard I.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Kaufman, Charles K.; Zon, Leonard I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Kaufman, Charles K.; Ablain, Julien; van Rooijen, Ellen; Hagedorn, Elliott J.; Ciarlo, Christie; Liao, Eric C.; Zon, Leonard I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mosimann, Christian] Univ Zurich, Inst Mol Life Sci, CH-8057 Zurich, Switzerland. [Fan, Zi Peng; Young, Richard A.] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. [Fan, Zi Peng] MIT, Computat & Syst Biol Program, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [White, Richard M.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY 10075 USA. [Matos, Dominick A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. [Puller, Ann-Christin] Childrens Canc Ctr Hamburg, Inst Res, D-20246 Hamburg, Germany. [Puller, Ann-Christin] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, D-20246 Hamburg, Germany. [Santoriello, Cristina; Zon, Leonard I.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Liao, Eric C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Young, Richard A.] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Zon, LI (reprint author), Childrens Hosp Boston, Howard Hughes Med Inst, Stem Cell Program, Boston, MA 02115 USA.; Zon, LI (reprint author), Childrens Hosp Boston, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA.; Zon, LI (reprint author), Harvard Stem Cell Inst, Boston, MA 02115 USA.; Zon, LI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Zon, LI (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Zon, LI (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM zon@enders.tch.harvard.edu RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [K08 AR061071]; European Molecular Biology Organization; Human Frontier Science Program; Swiss National Science Foundation; Ellison Foundation; V Foundation; Melanoma Research Alliance; Howard Hughes Medical Institute; NIH [HG002668]; [R01 CA103846] FX C.K.K. and research reported here is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award K08 AR061071. C.M. received support from a European Molecular Biology Organization long-term fellowship, a Human Frontier Science Program long-term fellowship, and a Swiss National Science Foundation advanced postdoctoral fellowship. L.I.Z. is supported by R01 CA103846, the Ellison Foundation, the V Foundation, and the Melanoma Research Alliance and is a Howard Hughes Medical Institute Investigator. R.A.Y. is supported by NIH HG002668. Z.P.F. was supported by NIH HG002668. E.J.H. is a Howard Hughes Medical Institute Fellow of the Helen Hay Whitney Foundation. L.I.Z. is a founder and stock holder of Fate, Inc. and Scholar Rock. R.A.Y. is a founder of Syros Pharmaceuticals. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank the Massachusetts General Hospital DNA Core for providing technical assistance with deep sequencing. We thank J. Ablain for critical review of the manuscript, C. Ceol for the gift of the zebrafish mitfa middle entry clone, and G. Musso for helpful discussions on microarray data and GSEA. All microarray, Chip-seq, and RNA-seq are deposited at Gene Expression Omnibus, ID GSE75356. NR 53 TC 24 Z9 24 U1 9 U2 31 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 29 PY 2016 VL 351 IS 6272 AR aad2197 DI 10.1126/science.aad2197 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB9SW UT WOS:000368858200026 ER PT J AU Latif, R Lau, Z Cheung, P Felsenfeld, DP Davies, TF AF Latif, Rauf Lau, Zerlina Cheung, Pamela Felsenfeld, Dan P. Davies, Terry F. TI The "TSH Receptor Glo Assay" - A High-Throughput Detection System for Thyroid Stimulation SO FRONTIERS IN ENDOCRINOLOGY LA English DT Article DE TSH receptor; small molecule; screening; high-throughput; thyroid-stimulating hormone ID SMALL-MOLECULE AGONISTS; THYROTROPIN RECEPTOR; GRAVES-DISEASE; HORMONE; AUTOANTIBODIES; EXPRESSION; CLEAVAGE; ANTIBODY; BINDING AB Background: To identify novel small molecules against the TSH receptor, we developed a sensitive transcription-based luciferase high-throughput screening (HIS) system named the TSHR-Glo Assay (TSHR-Glo). Methods: This assay uses double-transfected Chinese hamster ovary cells stably expressing the human TSHR and a cAMP-response element (CRE) construct fused to an improved luciferase reporter gene. Results: The assay was highly responsive toward TSH in a dose-dependent manner with a TSH sensitivity of 10(-10)M (10 +/- 1.12 mu U/ml) and thyroid-stimulating antibodies, a hallmark of Graves' disease, could also be detected. The assay was validated against the standard indicator of HTS performance - the Z-factor (Z') - producing a score of 0.895. Using the TSHR-Glo assay, we screened 48,224 compounds from a diverse chemical library in duplicate plates at a fixed dose of 17 mu M. Twenty molecules with the greatest activity out of 62 molecules that were identified by this technique were subsequently screened against the parent luciferase stable cell line in order to eliminate false positive stimulators. Conclusion: Using this approach, we were able to identify specific agonists against the TSH receptor leading to the characterization of several TSH agonist molecules. Hence, the TSHR-Glo assay was a one-step cell-based HTS assay, which was successful in the discovery of novel small molecular agonists and for the detection of stimulating antibodies to the TSH receptor. C1 [Latif, Rauf; Davies, Terry F.] Icahn Sch Med Mt Sinai, Dept Med, Thyroid Res Unit, New York, NY 10029 USA. [Latif, Rauf; Davies, Terry F.] James J Peters VA Med Ctr, New York, NY USA. [Lau, Zerlina; Cheung, Pamela; Felsenfeld, Dan P.] Icahn Sch Med Mt Sinai, Integrated Screening Core, Expt Therapeut Inst, New York, NY 10029 USA. RP Latif, R (reprint author), Icahn Sch Med Mt Sinai, Dept Med, Thyroid Res Unit, New York, NY 10029 USA.; Latif, R (reprint author), James J Peters VA Med Ctr, New York, NY USA. EM rauf.latif@mssm.edu FU NIH [DK069713, DK052464]; David Owen Segal Fund; VA Merit Award program FX This work was supported in part by NIH grants DK069713 and DK052464, the David Owen Segal Fund, and the VA Merit Award program (to TD). NR 30 TC 1 Z9 1 U1 5 U2 7 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2392 J9 FRONT ENDOCRINOL JI Front. Endocrinol. PD JAN 28 PY 2016 VL 7 AR 3 DI 10.3389/fendo.2016.00003 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP4XY UT WOS:000378501800001 PM 26858688 ER PT J AU Lehavot, K Williams, EC Millard, SP Bradley, KA Simpson, TL AF Lehavot, Keren Williams, Emily C. Millard, Steven P. Bradley, Katharine A. Simpson, Tracy L. TI Association of Alcohol Misuse With Sexual Identity and Sexual Behavior in Women Veterans SO SUBSTANCE USE & MISUSE LA English DT Article DE sexual orientation; AUDIT-C; lesbian and bisexual women; Women veterans; alcohol disparities ID SERVICES-TASK-FORCE; SUBSTANCE USE; MENTAL-HEALTH; ORIENTATION DISPARITIES; DRINKING CONTEXTS; MINORITY VETERANS; BISEXUAL WOMEN; UNITED-STATES; ADULT HEALTH; YOUNG-ADULTS AB Background: Sexual minority women report greater alcohol misuse than heterosexual women in the general population, with more pronounced differences found among younger age groups. It is unknown whether these differences exist among women veterans. Objective: We evaluated differences in alcohol misuse across two dimensions of sexual orientation (identity and behavior) among women veterans, and examined whether these differences were modified by age. Methods: Women veterans were recruited via the internet to participate in an online survey. Participants provided information on their self-reported sexual identity and behavior and responded to the validated 3-item Alcohol Use Disorders Identification Test-Consumption questionnaire (AUDIT-C). Regression models were used to compare the prevalence of alcohol misuse (AUDIT-C >= 3) and severity (AUDIT-C scores) across sexual identity and behavior and to test effect modification by age. Results: Among the 702 participants (36% lesbian/bisexual), prevalence and severity of alcohol misuse varied by both sexual identity and behavior, but there were significant interactions with age. Prevalence and severity of alcohol misuse were higher among relatively younger self-identified lesbians compared to heterosexual women. Similarly, both prevalence and severity of alcohol misuse were generally higher among younger women who had any sex with women compared to those who had sex only with men. Conclusions/Importance: In this online study of women veterans, younger sexual minority women were more likely to screen positive for alcohol misuse, and they had more severe alcohol misuse, than their heterosexual counterparts. Prevention and treatment efforts focused specifically on sexual minority women veterans may be needed. C1 [Lehavot, Keren; Williams, Emily C.; Bradley, Katharine A.] VA Puget Sound, VA Hlth Serv Res & Dev, Denver Seattle Ctr Innovat Vet Ctr & Value Driven, Seattle, WA USA. [Lehavot, Keren; Millard, Steven P.; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr MIRECC, Seattle, WA 98108 USA. [Lehavot, Keren; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Lehavot, Keren; Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. RP Lehavot, K (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, 1660 S Columbian Way,116-POC, Seattle, WA 98108 USA. EM klehavot@uw.edu FU VISN-20 Mental Illness Research, Education, and Clinical Center (MIRECC); VA Career Development Award from CSRD [CX000867]; VA Career Development Award from HSRD [CDA 12-276] FX This research was supported by a research grant to K. Lehavot and T. Simpson from the VISN-20 Mental Illness Research, Education, and Clinical Center (MIRECC). Drs. Lehavot and Williams are supported by VA Career Development Awards from CSR&D (CX000867) and HSR&D (CDA 12-276), respectively. NR 45 TC 0 Z9 0 U1 4 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PD JAN 28 PY 2016 VL 51 IS 2 BP 216 EP 229 DI 10.3109/10826084.2015.1092988 PG 14 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA DE3YX UT WOS:000370567500008 PM 26800263 ER PT J AU Duda, T Pertzev, A Makino, CL Sharma, RK AF Duda, Teresa Pertzev, Alexandre Makino, Clint L. Sharma, Rameshwar K. TI Bicarbonate and Ca2+ Sensing Modulators Activate Photoreceptor ROS-GC1 Synergistically SO FRONTIERS IN MOLECULAR NEUROSCIENCE LA English DT Article DE bicarbonate; calcium-binding protein; guanylate cyclase (guanylyl cyclase); guanylate cyclase; activating protein (GCAP); phototransduction; S100 proteins; signal transduction; second messenger ID MEMBRANE GUANYLATE-CYCLASE; LEBER CONGENITAL AMAUROSIS; NATRIURETIC-FACTOR-RECEPTOR; SIGNAL-TRANSDUCTION; PROTEINS GCAPS; FUNCTIONAL-CHARACTERIZATION; DIMERIZATION DOMAIN; ELECTRON-MICROSCOPY; CARBONIC-ANHYDRASE; NEUROCALCIN-DELTA AB Photoreceptor ROS-GC1 a prototype subfamily member of the membrane guanylate cyclase family, is a central component of phototransduction. It is a single transmembrane-spanning protein, composed of modular blocks. In rods, guanylate cyclase activating proteins (GCAPs) 1 and 2 bind to its juxtamembrane domain (JMD) and the C-terminal extension, respectively, to accelerate cyclic GMP synthesis when Ca2+ levels are low. In cones, the additional expression of the Ca2+-dependent guanylate cyclase activating protein (CD-GCAP) S100B which binds to its C-terminal extension, supports acceleration of cyclic GMP synthesis at high Ca2+ levels. Independent of Cat(2+), ROS-GC1 activity is also stimulated directly by bicarbonate binding to the core catalytic domain (CCD). Several enticing molecular features of this transduction system are revealed in the present study. In combination, bicarbonate and Ca2+ I-dependent modulators raised maximal ROS-GC activity to levels that exceeded the sum of their individual effects. The F514S mutation in ROS-GC1 that causes blindness in type 1 Leber's congenital amaurosis (LCA) severely reduced basal ROS-GC1 activity. GCAP2 and S100B Cat(2+) signaling modes remained functional, while the GCAP1-modulated mode was diminished. Bicarbonate nearly restored basal activity as well as GCAP2- and S100B-stimulated activities of the F514S mutant to normal levels but could not resurrect GCAP1 stimulation. We conclude that GCAP1 and GCAP2 forge distinct pathways through domain-specific modules of ROS-GC1 whereas the S100B and GCAP2 pathways may overlap. The synergistic interlinking of bicarbonate to GCAPs- and S100B-modulated pathways intensifies and tunes the dependence of cyclic GMP synthesis on intracellular Ca2+. Our study challenges the recently proposed GCAP1 and GCAP2 "overlapping" phototransduction model (Peshenko et al., 2015b). C1 [Duda, Teresa; Pertzev, Alexandre; Sharma, Rameshwar K.] Salus Univ, Unit Regulatory & Mol Biol, Div Biochem Res, Elkins Pk, PA USA. [Duda, Teresa; Pertzev, Alexandre; Sharma, Rameshwar K.] Salus Univ, Unit Regulatory & Mol Biol, Res Div Mol Biol, Elkins Pk, PA USA. [Makino, Clint L.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Makino, Clint L.] Harvard Univ, Sch Med, Boston, MA USA. RP Duda, T (reprint author), Salus Univ, Unit Regulatory & Mol Biol, Div Biochem Res, Elkins Pk, PA USA.; Duda, T (reprint author), Salus Univ, Unit Regulatory & Mol Biol, Res Div Mol Biol, Elkins Pk, PA USA. EM tduda@salus.edu FU National Eye Institute [EY023980, EY014104]; Howe Laboratory Endowment of the Massachusetts Eye and Ear Infirmary; Research to Prevent Blindness, Inc. FX This work was supported by the National Eye Institute: EY023980, EY014104, the Howe Laboratory Endowment of the Massachusetts Eye and Ear Infirmary, and by Research to Prevent Blindness, Inc. The authors are solely responsible for the contents of this article, which do not necessarily represent the official views of the National Eye Institute. NR 63 TC 1 Z9 1 U1 0 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5099 J9 FRONT MOL NEUROSCI JI Front. Molec. Neurosci. PD JAN 28 PY 2016 VL 9 AR 5 DI 10.3389/fnmol.2013.00005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA DE3UF UT WOS:000370555100001 PM 26858600 ER PT J AU Li, JZ Etemad, B Ahmed, H Aga, E Bosch, RJ Mellors, JW Kuritzkes, DR Lederman, MM Para, M Gandhi, RT AF Li, Jonathan Z. Etemad, Behzad Ahmed, Hayat Aga, Evgenia Bosch, Ronald J. Mellors, John W. Kuritzkes, Daniel R. Lederman, Michael M. Para, Michael Gandhi, Rajesh T. TI The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption SO AIDS LA English DT Article DE biomarker; expressed reservoir; HIV; monitored antiretroviral pause; treatment interruption; viral rebound ID SUPPRESSIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; PCR ASSAY; INFECTION; REPLICATION; TRIALS; LATENCY; PLASMA; TIME; CURE AB Objectives:Therapies to achieve sustained antiretroviral therapy-free HIV remission will require validation in analytic treatment interruption (ATI) trials. Identifying biomarkers that predict time to viral rebound could accelerate the development of such therapeutics.Design:A pooled analysis of participants from six AIDS Clinical Trials Group ATI studies to identify predictors of viral rebound.Methods:Cell-associated DNA (CA-DNA) and CA-RNA were quantified in pre-ATI peripheral blood mononuclear cell samples, and residual plasma viremia was measured using the single-copy assay.Results:Participants who initiated antiretroviral therapy (ART) during acute/early HIV infection and those on a non-nucleoside reverse transcriptase inhibitor-containing regimen had significantly delayed viral rebound. Participants who initiated ART during acute/early infection had lower levels of pre-ATI CA-RNA (acute/early vs. chronic-treated: median <92 vs. 156 HIV-1 RNA copies/10(6) CD4(+) cells, P<0.01). Higher pre-ATI CA-RNA levels were significantly associated with shorter time to viral rebound (4 vs. 5-8 vs. >8 weeks: median 182 vs. 107 vs. <92 HIV-1 RNA copies/10(6) CD4(+) cells, Kruskal-Wallis P<0.01). The proportion of participants with detectable plasma residual viremia prior to ATI was significantly higher among those with shorter time to viral rebound.Conclusion:Higher levels of HIV expression while on ART are associated with shorter time to HIV rebound after treatment interruption. Quantification of the active HIV reservoir may provide a biomarker of efficacy for therapies that aim to achieve ART-free HIV remission. C1 [Li, Jonathan Z.; Etemad, Behzad; Ahmed, Hayat; Kuritzkes, Daniel R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cambridge, MA 02138 USA. [Aga, Evgenia; Bosch, Ronald J.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Mellors, John W.] Univ Pittsburgh, Pittsburgh, PA USA. [Lederman, Michael M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Para, Michael] Ohio State Univ, Columbus, OH 43210 USA. [Gandhi, Rajesh T.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gandhi, Rajesh T.] Harvard Univ, Sch Med, Ragon Inst, Boston, MA 02115 USA. RP Li, JZ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Cambridge, MA 02138 USA.; Li, JZ (reprint author), Brigham & Womens Hosp, Div Infect Dis, 65 Landsdowne St,Rm 421, Cambridge, MA 02139 USA. EM jli@bwh.harvard.edu FU Harvard University Center for AIDS Research [NIAID 5P30AI060354-08]; National Institutes of Health (NIH) [AI100699, AI36219, UM1 AI068634, UM1 AI068636] FX This work was supported in part by a grant from the Harvard University Center for AIDS Research (to J.Z.L. and R.T.G., NIAID 5P30AI060354-08), National Institutes of Health (NIH) grants AI100699 (to J.Z.L.), AI36219 (to M.M.L.), UM1 AI068634 (Statistical and Data Management Center of the AIDS Clinical Trials Group), UM1 AI068636 (AIDS Clinical Trials Group), and a subcontract from UM1 AI068636 to the Harvard Virology Support Laboratory (to D.R.K.). NR 45 TC 15 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 28 PY 2016 VL 30 IS 3 BP 343 EP 353 DI 10.1097/QAD.0000000000000953 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DC6BN UT WOS:000369304800002 PM 26588174 ER PT J AU Looby, SE Fitch, KV Srinivasa, S Lo, J Rafferty, D Martin, A Currier, JC Grinspoon, S Zanni, MV AF Looby, Sara E. Fitch, Kathleen V. Srinivasa, Suman Lo, Janet Rafferty, Danielle Martin, Amanda Currier, Judith C. Grinspoon, Steven Zanni, Markella V. TI Reduced ovarian reserve relates to monocyte activation and subclinical coronary atherosclerotic plaque in women with HIV SO AIDS LA English DT Article DE cardiovascular diseases; HIV; menopause; ovarian reserve; women ID ANTI-MULLERIAN HORMONE; RISK-FACTORS; ANTIMULLERIAN HORMONE; NATURAL MENOPAUSE; INFECTED PATIENTS; HEART-DISEASE; ANGIOGRAPHY; SYMPTOMS; COCAINE; MARKER AB Objective:To investigate differences in subclinical coronary atherosclerotic plaque and markers of immune activation among HIV-infected and non-HIV-infected women categorized by degree of ovarian reserve and menopause status. Design:Cross-sectional evaluation. Methods:Seventy-four women (49 HIV-infected, 25 non-HIV-infected) without known cardiovascular disease (CVD) were classified as premenopausal, premenopausal with reduced ovarian reserve, or postmenopausal based on menstrual history and anti-Mullerian hormone (AMH) levels. Participants underwent contrast-enhanced coronary computed tomography angiography and immune phenotyping. Comparisons in coronary atherosclerotic plaque burden and immune markers were made between the HIV-infected and non-HIV-infected women overall and within the HIV-infected and non-HIV-infected women by reproductive classification group. Results:Among the overall group of HIV-infected women, the women with reduced ovarian reserve (undetectable AMH) had a higher prevalence of coronary atherosclerotic plaque (52 versus 6%, P=0.0007) and noncalcified plaque (48 versus 6%, P=0.002), as well as higher levels of log sCD163 (P=0.0004) and log MCP-1 (P=0.006), compared with the premenopausal women with measurable AMH. Furthermore, reduced ovarian reserve in the HIV-infected group related to noncalcified plaque, controlling for traditional CVD risk factors (P=0.04) and sCD163 (P=0.03). Conclusion:HIV-infected women with reduced ovarian reserve have increased subclinical coronary atherosclerotic plaque compared with premenopausal women in whom AMH is measurable. This relationship holds when controlling for CVD risk factors (including age) and immune activation. Our findings demonstrate that reduced ovarian reserve may contribute to CVD burden in HIV-infected women and support a comprehensive assessment of CVD risk prior to completion of menopause in this population. C1 [Looby, Sara E.; Fitch, Kathleen V.; Srinivasa, Suman; Lo, Janet; Rafferty, Danielle; Martin, Amanda; Grinspoon, Steven; Zanni, Markella V.] Massachusetts Gen Hosp, Program Nutr Metab, 5 Longfellow Pl,Suite 207,55 Fruit St, Boston, MA 02114 USA. [Looby, Sara E.; Fitch, Kathleen V.; Srinivasa, Suman; Lo, Janet; Rafferty, Danielle; Martin, Amanda; Grinspoon, Steven; Zanni, Markella V.] Harvard Univ, Sch Med, Boston, MA USA. [Currier, Judith C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Zanni, MV (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 5 Longfellow Pl,Suite 207,55 Fruit St, Boston, MA 02114 USA.; Zanni, MV (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Zanni, MV (reprint author), Massachusetts Gen Hosp, 5 Longfellow Pl,Suite 207,55 Fruit St, Boston, MA 02114 USA. EM mzanni@mgh.harvard.edu FU Bristol Myers Squibb, Inc; National Institutes of Health [R01 HL095123-04, M01-RR-01066, 1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources; Nutrition Obesity Research Center at Harvard [P30 DK040561] FX This work was supported by Bristol Myers Squibb, Inc and the National Institutes of Health and R01 HL095123-04 to S.G., M01-RR-01066 and 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center, from the National Center for Research Resources and P30 DK040561, Nutrition Obesity Research Center at Harvard. Funding sources had no role in the design of the study, data analysis or the writing of the manuscript. NR 37 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 28 PY 2016 VL 30 IS 3 BP 383 EP 393 DI 10.1097/QAD.0000000000000902 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DC6BQ UT WOS:000369305100003 PM 26696388 ER PT J AU Depp, TB McGinnis, KA Kraemer, K Akgun, KM Edelman, EJ Fiellin, DA Butt, AA Crystal, S Gordon, AJ Freiberg, M Gibert, CL Rimland, D Bryant, KJ Crothers, K AF Depp, Timothy B. McGinnis, Kathleen A. Kraemer, Kevin Akguen, Kathleen M. Edelman, E. Jennifer Fiellin, David A. Butt, Adeel A. Crystal, Stephen Gordon, Adam J. Freiberg, Matthew Gibert, Cynthia L. Rimland, David Bryant, Kendall J. Crothers, Kristina TI Risk factors associated with acute exacerbation of chronic obstructive pulmonary disease in HIV-infected and uninfected patients SO AIDS LA English DT Article DE acute exacerbation; AECOPD; AIDS/HIV; chronic obstructive pulmonary disease; cigarette smoking; COPD; tobacco use; unhealthy alcohol use ID ANTIRETROVIRAL THERAPY ERA; COPD EXACERBATIONS; UNITED-STATES; LUNG-DISEASE; ALCOHOL-USE; CARE; HEALTH; VETERANS; EPIDEMIOLOGY; MORTALITY AB Objective:To determine the association between HIV infection and other risk factors for acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Design:Longitudinal, national Veterans Aging Cohort Study including 43 618 HIV-infected and 86 492 uninfected veterans.Methods:AECOPD was defined as an inpatient or outpatient COPD ICD-9 diagnosis accompanied by steroid and/or antibiotic prescription within 5 days. We calculated incidence rate ratios (IRR) and 95% confidence intervals (CI) for first AECOPD over 2 years and used Poisson regression models to adjust for risk factors.Results:Over 234099 person-years of follow-up, 1428 HIV-infected and 2104 uninfected patients had at least one AECOPD. HIV-infected patients had an increased rate of AECOPD compared with uninfected (18.8 vs. 13.3 per 1000 person-years, P<0.001). In adjusted models, AECOPD risk was greater in HIV-infected individuals overall (IRR 1.54; 95% CI 1.44-1.65), particularly in those with more severe immune suppression when stratified by CD4(+) cell count (cells/l) compared with uninfected (HIV-infected CD4(+)<200: IRR 2.30, 95% CI 2.10-2.53, HIV-infected CD4(+) 200-349: IRR 1.32, 95% CI 1.15-1.51, HIV-infected CD4(+)350: IRR 0.99, 95% CI 0.88-1.10). HIV infection also modified the association between current smoking and alcohol-related diagnoses with risk for AECOPD such that interaction terms for HIV and current smoking or HIV and alcohol-related diagnoses were each significantly associated with AECOPD.Conclusion:HIV infection, especially with lower CD4(+) cell count, is an independent risk factor for AECOPD. Enhanced susceptibility to harm from current smoking or unhealthy alcohol use in HIV-infected patients may also contribute to the greater rate of AECOPD. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved. C1 [Depp, Timothy B.] Univ S Carolina, Columbia, SC 29208 USA. [Depp, Timothy B.; McGinnis, Kathleen A.; Kraemer, Kevin; Butt, Adeel A.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kraemer, Kevin; Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Akguen, Kathleen M.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Akguen, Kathleen M.; Edelman, E. Jennifer; Fiellin, David A.] Yale Univ, Sch Med, New Haven, CT USA. [Butt, Adeel A.] Hamad Healthcare Qual Inst, Doha, Qatar. [Butt, Adeel A.] Hamad Med Corp, Doha, Qatar. [Crystal, Stephen] Rutgers State Univ, New Brunswick, NJ 08903 USA. [Freiberg, Matthew] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Gibert, Cynthia L.] Washington DC VA Med Ctr, Washington, DC USA. [Rimland, David] VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Bryant, Kendall J.] NIAAA, NIH, Bethesda, MD USA. [Crothers, Kristina] Univ Washington, Seattle, WA 98195 USA. RP Crothers, K (reprint author), Univ Washington, Harborview Med Ctr, 325 9th Ave,POB 359762, Seattle, WA 98104 USA. EM crothk@uw.edu OI Edelman, E. Jennifer/0000-0002-9375-0489; Fiellin, David/0000-0002-4006-010X; Crothers, Kristina/0000-0001-9702-0371 FU NIH/NHLBI [R01 HL090342]; NIAAA [U24-AA020794]; AHRQ [U19HS021, R18HS023258, U10 AA013566] FX NIH/NHLBI R01 HL090342, NIAAA U24-AA020794, AHRQ U19HS021, R18HS023258 and U10 AA013566. NR 69 TC 5 Z9 5 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 28 PY 2016 VL 30 IS 3 BP 455 EP 463 DI 10.1097/QAD.0000000000000940 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DC6CB UT WOS:000369306300003 PM 26765938 ER PT J AU Maus, MV AF Maus, Marcela V. TI Innate immune signaling in CLL SO BLOOD LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA C1 [Maus, Marcela V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Maus, MV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 28 PY 2016 VL 127 IS 4 BP 376 EP + DI 10.1182/blood-2015-11-679845 PG 3 WC Hematology SC Hematology GA DC5VI UT WOS:000369288300004 PM 26823508 ER PT J AU Clapham, KR Chu, AY Wessel, J Natarajan, P Flannick, J Rivas, MA Sartori, S Mehran, R Baber, U Fuster, V Scott, RA Rader, DJ Boehnke, M McCarthy, MI Altshuler, DM Kathiresan, S Peloso, GM AF Clapham, Katharine R. Chu, Audrey Y. Wessel, Jennifer Natarajan, Pradeep Flannick, Jason Rivas, Manuel A. Sartori, Samantha Mehran, Roxana Baber, Usman Fuster, Valentin Scott, Robert A. Rader, Daniel J. Boehnke, Michael McCarthy, Mark I. Altshuler, David M. Kathiresan, Sekar Peloso, Gina M. TI A null mutation in ANGPTL8 does not associate with either plasma glucose or type 2 diabetes in humans SO BMC ENDOCRINE DISORDERS LA English DT Article DE Betatrophin; Angiopoietin-like 8; rs145464906 ID LOW-FREQUENCY; VARIANTS; ANGPTL8/BETATROPHIN; SUSCEPTIBILITY; BETATROPHIN; PROTEIN; DISEASE; DESIGN AB Background: Experiments in mice initially suggested a role for the protein angiopoietin-like 8 (ANGPTL8) in glucose homeostasis. However, subsequent experiments in model systems have challenged this proposed role. We sought to better understand the importance of ANGPTL8 in human glucose homeostasis by examining the association of a null mutation in ANGPTL8 with fasting glucose levels and risk for type 2 diabetes. Methods: A naturally-occurring null mutation in human ANGPTL8 (rs145464906; c.361C > T; p.Q121X) is carried by similar to 1 in 1000 individuals of European ancestry and is associated with higher levels of plasma high-density lipoprotein cholesterol, suggesting that this mutation has functional significance. We examined the association of p.Q121X with fasting glucose levels and risk for type 2 diabetes in up to 95,558 individuals (14,824 type 2 diabetics and 80,734 controls). Results: We found no significant association of p.Q121X with either fasting glucose or type 2 diabetes (p-value = 0.90 and 0.65, respectively). Given our sample sizes, we had >98 % power to detect at least a 0.23 mmol/L effect on plasma glucose and >95 % power to detect a 70 % increase in risk for type 2 diabetes. Conclusion: Disruption of ANGPTL8 function in humans does not seem to have a large effect on measures of glucose tolerance. C1 [Clapham, Katharine R.; Natarajan, Pradeep; Rivas, Manuel A.; Kathiresan, Sekar; Peloso, Gina M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Chu, Audrey Y.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Chu, Audrey Y.] Natl Heart Lung & Blood Inst NHLBI Framingham Hea, Framingham, MA 01702 USA. [Wessel, Jennifer] Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46202 USA. [Wessel, Jennifer] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Natarajan, Pradeep; Kathiresan, Sekar; Peloso, Gina M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Natarajan, Pradeep; Kathiresan, Sekar; Peloso, Gina M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Natarajan, Pradeep; Flannick, Jason; Rivas, Manuel A.; Altshuler, David M.; Kathiresan, Sekar; Peloso, Gina M.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Flannick, Jason; Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sartori, Samantha; Mehran, Roxana; Baber, Usman; Fuster, Valentin] Icahn Sch Med Mt Sinai, Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. [Scott, Robert A.] Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 0SL, England. [Rader, Daniel J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Altshuler, David M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Peloso, Gina M.] Crosstown Ctr, 801 Massachusetts Ave,Third Floor, Boston, MA 02118 USA. RP Peloso, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.; Peloso, GM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.; Peloso, GM (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.; Peloso, GM (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Peloso, GM (reprint author), Crosstown Ctr, 801 Massachusetts Ave,Third Floor, Boston, MA 02118 USA. EM gpeloso@bu.edu RI Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Natarajan, Pradeep/0000-0001-8402-7435; Wessel, Jennifer/0000-0002-7031-0085 FU National Heart, Lung, and Blood Institute of National Institutes of Health [K01HL125751]; Research Scholar award from Massachusetts General Hospital (MGH); Howard Goodman Fellowship from MGH; Donovan Family Foundation [R01HL107816]; Fondation Leducq FX GMP is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K01HL125751. SK is supported by a Research Scholar award from the Massachusetts General Hospital (MGH), the Howard Goodman Fellowship from MGH, the Donovan Family Foundation, R01HL107816, and a grant from Fondation Leducq. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors do not report any conflict of interest. NR 15 TC 1 Z9 1 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6823 J9 BMC ENDOCR DISORD JI BMC Endocr. Disord. PD JAN 28 PY 2016 VL 16 AR 7 DI 10.1186/s12902-016-0088-8 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DC4UO UT WOS:000369216000001 PM 26822414 ER PT J AU Rouch, JD Scott, A Lei, NY Solorzano-Vargas, RS Wang, JF Hanson, EM Kobayashi, M Lewis, M Stelzner, MG Dunn, JCY Eckmann, L Martin, MG AF Rouch, Joshua D. Scott, Andrew Lei, Nan Ye Solorzano-Vargas, R. Sergio Wang, Jiafang Hanson, Elaine M. Kobayashi, Masae Lewis, Michael Stelzner, Matthias G. Dunn, James C. Y. Eckmann, Lars Martin, Martin G. TI Development of Functional Microfold (M) Cells from Intestinal Stem Cells in Primary Human Enteroids SO PLOS ONE LA English DT Article ID EPITHELIAL M-CELLS; PATCH M-CELLS; NF-KAPPA-B; MESENCHYMAL TRANSITION; TRANSEPITHELIAL TRANSPORT; MOUSE INTESTINE; PEYERS-PATCHES; IN-VITRO; DIFFERENTIATION; EXPRESSION AB Background & Aims Intestinal microfold (M) cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs), and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting. Methods Human intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium. Results Functional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose-and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2) in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells. Conclusions Human intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an in vitro setting. We anticipate that this model can be used to generate large numbers of M cells for further functional studies of these key cells of intestinal immune induction and their impact on controlling enteric pathogens and the intestinal microbiome. C1 [Rouch, Joshua D.; Scott, Andrew; Dunn, James C. Y.] Univ Calif Los Angeles, Dept Surg, Div Pediat Surg, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Lei, Nan Ye; Kobayashi, Masae; Dunn, James C. Y.] Univ Calif Los Angeles, Dept Bioengn, Henry Samueli Sch Engn, Los Angeles, CA USA. [Solorzano-Vargas, R. Sergio; Wang, Jiafang; Martin, Martin G.] Univ Calif Los Angeles, Dept Pediat, Div Gastroenterol & Nutr, Mattel Childrens Hosp, Los Angeles, CA 90024 USA. [Solorzano-Vargas, R. Sergio; Wang, Jiafang; Martin, Martin G.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hanson, Elaine M.; Eckmann, Lars] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Lewis, Michael] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. [Stelzner, Matthias G.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Martin, Martin G.] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA USA. RP Martin, MG (reprint author), Univ Calif Los Angeles, Dept Pediat, Div Gastroenterol & Nutr, Mattel Childrens Hosp, Los Angeles, CA 90024 USA.; Martin, MG (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.; Martin, MG (reprint author), Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA USA. EM mmartin@mednet.ucla.edu RI Solorano, Sergio/D-4869-2016 FU Intestinal Stem Cell Consortium - National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases [DK085535]; NIDDK [DK083762, DK083319]; California Institute for Regenerative Medicine [RT2-01985] FX This work was supported by the Intestinal Stem Cell Consortium (https://iscc.coh.org), a collaborative research project funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Allergy and Infectious Diseases (DK085535); and other grants from NIDDK (DK083762, and DK083319), and the California Institute for Regenerative Medicine (RT2-01985). NR 37 TC 3 Z9 3 U1 6 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 28 PY 2016 VL 11 IS 1 AR e0148216 DI 10.1371/journal.pone.0148216 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC9GF UT WOS:000369528400076 PM 26820624 ER PT J AU Natarajan, A Ahn, R Nelson, BD Eckardt, M Kamara, J Kargbo, S Kanu, P Burke, TF AF Natarajan, Abirami Ahn, Roy Nelson, Brett D. Eckardt, Melody Kamara, Jennifer Kargbo, Sas Kanu, Pity Burke, Thomas F. TI Use of prophylactic uterotonics during the third stage of labor: a survey of provider practices in community health facilities in Sierra Leone SO BMC PREGNANCY AND CHILDBIRTH LA English DT Article DE Prophylactic uterotonics; Postpartum hemorrhage; Sierra Leone ID ACTIVE MANAGEMENT; MATERNAL DEATH; STRATEGIES; TRIAL AB Background: Postpartum hemorrhage remains the leading cause of maternal mortality worldwide. Administration of uterotonics during the third stage of labor is a simple and well established intervention that can significantly decrease the development of postpartum hemorrhage. Little is known about the use of prophylactic uterotonics in peripheral health centers, where the majority of normal deliveries occur. The purpose of this study is to assess health provider current practices and determinants to the use of prophylactic uterotonics in Sierra Leone, a country with one of the highest maternal mortality ratios worldwide. Methods: This is a mixed methods study using descriptive cross-sectional survey and qualitative interviews in community health facilities in Freetown, Sierra Leone following a comprehensive training on postpartum hemorrhage. Facilities and providers were surveyed between May and June 2014. Qualitative methods were used to identify barriers and facilitators to the use of prophylactic uterotonics. Results: A total of 134 providers were surveyed at 39 periphreal health facilities. Thirteen facilities (39 %) reported an inconsistent supply of oxytocin. The majority of facilities (64 %) stored oxytocin at room temperature. Provider level, in-service training, and leadership role were significantly associated with prophylactic uterotonic use. Overall, 62 % of providers reported routine use. Midwives were most likely to routinely administer uterotonics (93 %), followed by community health officers/assistants (78 %), maternal and child health aides (56 %), and state-enrolled community health nurses (52 %). Of the providers who received in-service training, 67 % reported routine use; of those with no in-service training, 42 % reported routine use. Qualitative analysis revealed that facility protocols, widespread availability, and provider perception of utility facilitated routine use. Common barriers reported included inconsistent supply of uterotonics, lack of knowledge regarding timely administration, and provider attitude regarding utility of uterotonics following normal deliveries. Conclusion: There is considerable room for improvement in availability and administration of prophylactic uterotonics. Understanding barriers to routine use may aid in developing multifaceted pre-service and in-service training interventions designed to improve routine intrapartum care. C1 [Natarajan, Abirami; Ahn, Roy; Nelson, Brett D.; Eckardt, Melody; Kamara, Jennifer; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Zero Emerson Pl Suite 104, Boston, MA 02114 USA. [Natarajan, Abirami; Ahn, Roy; Nelson, Brett D.; Burke, Thomas F.] Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. [Kargbo, Sas; Kanu, Pity] Minist Hlth & Sanitat, 4th Floor Youyi Bldg, Freetown, Sierra Leone. RP Natarajan, A (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Zero Emerson Pl Suite 104, Boston, MA 02114 USA. EM abirami_natarajan@hms.harvard.edu OI Nelson, Brett/0000-0002-5049-1798 FU Saving Lives at Birth (Washington, DC, USA); Humanitarian Innovation Fund; Ujenzi Charitable Trust; Harvard Medical School (Boston, MA, USA) FX We would like to thank all of the health care providers who volunteered their time to work as UBT champions and all health care providers who participated in this study. We thank Tom Chittenden for his help with the statistical analysis. Funding was provided by Saving Lives at Birth (Washington, DC, USA), Humanitarian Innovation Fund, Ujenzi Charitable Trust, and Harvard Medical School (Boston, MA, USA). NR 19 TC 0 Z9 0 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2393 J9 BMC PREGNANCY CHILDB JI BMC Pregnancy Childbirth PD JAN 28 PY 2016 VL 16 AR 23 DI 10.1186/s12884-016-0809-z PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DB9YM UT WOS:000368873600001 PM 26821645 ER PT J AU Hu, H Juvekar, A Lyssiotis, CA Lien, EC Albeck, JG Oh, D Varma, G Hung, YP Ullas, S Lauring, J Seth, P Lundquist, MR Tolan, DR Grant, AK Needleman, DJ Asara, JM Cantley, LC Wulf, GM AF Hu, Hai Juvekar, Ashish Lyssiotis, Costas A. Lien, Evan C. Albeck, John G. Oh, Doogie Varma, Gopal Hung, Yin Pun Ullas, Soumya Lauring, Josh Seth, Pankaj Lundquist, Mark R. Tolan, Dean R. Grant, Aaron K. Needleman, Daniel J. Asara, John M. Cantley, Lewis C. Wulf, Gerburg M. TI Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton SO CELL LA English DT Article ID BREAST-CANCER; F-ACTIN; INHIBITOR; METABOLISM; ACTIVATION; PATHWAY; KINASE; CELLS; RAC; DEHYDROGENASE AB The phosphoinositide 3-kinase (PI3K) pathway regulates multiple steps in glucose metabolism and also cytoskeletal functions, such as cell movement and attachment. Here, we show that PI3K directly coordinates glycolysis with cytoskeletal dynamics in an AKT-independent manner. Growth factors or insulin stimulate the PI3K-dependent activation of Rac, leading to disruption of the actin cytoskeleton, release of filamentous actin-bound aldolase A, and an increase in aldolase activity. Consistently, PI3K inhibitors, but not AKT, SGK, or mTOR inhibitors, cause a significant decrease in glycolysis at the step catalyzed by aldolase, while activating PIK3CA mutations have the opposite effect. These results point toward a master regulatory function of PI3K that integrates an epithelial cell's metabolism and its form, shape, and function, coordinating glycolysis with the energy-intensive dynamics of actin remodeling. C1 [Hu, Hai; Juvekar, Ashish; Wulf, Gerburg M.] Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA. [Hu, Hai; Juvekar, Ashish; Wulf, Gerburg M.] Harvard Univ, Med Sch HMS, Boston, MA 02215 USA. [Lyssiotis, Costas A.; Lundquist, Mark R.; Cantley, Lewis C.] Weill Cornell Med, Meyer Canc Ctr, New York, NY 10065 USA. [Lien, Evan C.] BIDMC, Dept Pathol, Boston, MA 02215 USA. [Albeck, John G.] HMS, Dept Cell Biol, Boston, MA 02215 USA. [Oh, Doogie; Needleman, Daniel J.] Harvard Univ, FAS Ctr Syst Biol, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Varma, Gopal; Grant, Aaron K.] BIDMC Boston, Dept Radiol, Boston, MA 02215 USA. [Hung, Yin Pun] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Lauring, Josh] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Seth, Pankaj] BIDMC, Div Interdisciplinary Med, Boston, MA 02215 USA. [Tolan, Dean R.] Boston Univ, Dept Biol, Boston, MA 02215 USA. [Asara, John M.] BIDMC, Div Signal Transduct, Boston, MA 02215 USA. [Ullas, Soumya] BIDMC, Longwood Small Anim Imaging Facil, Boston, MA 02215 USA. [Lyssiotis, Costas A.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Albeck, John G.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA. RP Wulf, GM (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA.; Wulf, GM (reprint author), Harvard Univ, Med Sch HMS, Boston, MA 02215 USA. EM gwulf@bidmc.harvard.edu RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Lien, Evan/0000-0001-7866-4761; Lauring, Josh/0000-0002-4312-704X FU Breast Cancer Research Foundation (BCRF); Mary Kay Ash Foundation; Men's Initiative of DFHCC; Breast Cancer Alliance; NIH [GM041890, R21 EB014471, R01 CA169470]; NIH NCI [5P01CA120964-05, 5P30CA006516-46]; NSF [DBI-0959721, DMR-0820484]; United States-Israel Binational Science Foundation (BSF) [2009271]; Damon Runyon Cancer Research Foundation; Stand Up to Cancer Dream Team Translational Research Grant [SU2C-AACR-DT0209]; [R01CA152330-0] FX L.C.C. and G.M.W. are supported by a Stand Up to Cancer Dream Team Translational Research Grant, (SU2C-AACR-DT0209), by the Breast Cancer Research Foundation (BCRF), the Mary Kay Ash Foundation, the Men's Initiative of DFHCC, and the Breast Cancer Alliance; L.C.C. by NIH grant GM041890; J.M.A. in part by NIH NCI grants 5P01CA120964-05 and 5P30CA006516-46; A.K.G., P.S., and G.V. in part by NIH R21 EB014471 and R01 CA169470; and P.S. in part by R01CA152330-0. D.J.N. is supported in part by NSF DBI-0959721 and DMR-0820484 and the United States-Israel Binational Science Foundation (BSF 2009271); and C.A.L. by a Dale F. Frey award from the Damon Runyon Cancer Research Foundation. NR 36 TC 11 Z9 12 U1 12 U2 33 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 28 PY 2016 VL 164 IS 3 BP 433 EP 446 DI 10.1016/j.cell.2015.12.042 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DC0KU UT WOS:000368906800014 PM 26824656 ER PT J AU Haradhvala, NJ Polak, P Stojanov, P Covington, KR Shinbrot, E Hess, JM Rheinbay, E Kim, J Maruvka, YE Braunstein, LZ Kamburov, A Hanawalt, PC Wheeler, DA Koren, A Lawrence, MS Getz, G AF Haradhvala, Nicholas J. Polak, Paz Stojanov, Petar Covington, Kyle R. Shinbrot, Eve Hess, Julian M. Rheinbay, Esther Kim, Jaegil Maruvka, Yosef E. Braunstein, Lior Z. Kamburov, Atanas Hanawalt, Philip C. Wheeler, David A. Koren, Amnon Lawrence, Michael S. Getz, Gad TI Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair SO CELL LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; 21 BREAST CANCERS; SOMATIC MUTATIONS; REPLICATION; SIGNATURES; EVOLUTION; GENES; MUTAGENESIS; PATTERNS; ORIGINS AB Mutational processes constantly shape the somatic genome, leading to immunity, aging, cancer, and other diseases. When cancer is the outcome, we are afforded a glimpse into these processes by the clonal expansion of the malignant cell. Here, we characterize a less explored layer of the mutational landscape of cancer: mutational asymmetries between the two DNA strands. Analyzing whole-genome sequences of 590 tumors from 14 different cancer types, we reveal widespread asymmetries across mutagenic processes, with transcriptional ("T-class'') asymmetry dominating UV-, smoking-, and liver-cancer-associated mutations and replicative ("R-class'') asymmetry dominating POLE-, APOBEC-, and MSI-associated mutations. We report a striking phenomenon of transcription-coupled damage (TCD) on the non-transcribed DNA strand and provide evidence that APOBEC mutagenesis occurs on the lagging-strand template during DNA replication. As more genomes are sequenced, studying and classifying their asymmetries will illuminate the underlying biological mechanisms of DNA damage and repair. C1 [Haradhvala, Nicholas J.; Polak, Paz; Rheinbay, Esther; Maruvka, Yosef E.; Kamburov, Atanas; Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. [Haradhvala, Nicholas J.; Polak, Paz; Rheinbay, Esther; Maruvka, Yosef E.; Kamburov, Atanas; Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. [Haradhvala, Nicholas J.; Polak, Paz; Hess, Julian M.; Rheinbay, Esther; Kim, Jaegil; Maruvka, Yosef E.; Braunstein, Lior Z.; Kamburov, Atanas; Koren, Amnon; Lawrence, Michael S.; Getz, Gad] Broad Inst Harvard & MIT, 415 Main St, Cambridge, MA 02142 USA. [Polak, Paz; Kamburov, Atanas; Getz, Gad] Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. [Stojanov, Petar] Carnegie Mellon Univ, Sch Comp Sci, 5000 Forbes Ave, Pittsburgh, PA 15213 USA. [Covington, Kyle R.; Shinbrot, Eve; Wheeler, David A.] Baylor Coll Med, 1 Baylor Plaza, Houston, TX 77030 USA. [Hanawalt, Philip C.] Stanford Univ, Dept Biol, 450 Serra Mall, Stanford, CA 94305 USA. [Koren, Amnon] Cornell Univ, Dept Mol Biol & Genet, 526 Campus Rd, Ithaca, NY 14853 USA. RP Getz, G (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA.; Getz, G (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.; Lawrence, MS; Getz, G (reprint author), Broad Inst Harvard & MIT, 415 Main St, Cambridge, MA 02142 USA.; Getz, G (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM lawrence@broadinstitute.org; gadgetz@broadinstitute.org FU NIH TCGA Genome Data Analysis Center [U24CA143845]; NHGRI Genome Sequencing Center [U54HG003067]; NHGRI [U54HG003273]; G.G.'s startup funds at MGH FX We thank Ashok Bhagwat and Steven Roberts and their collaborators for sharing their unpublished data with us and allowing us to reference them in this work. We thank John Iafrate for valuable insights about the relevance of strand asymmetry in carcinogenesis. G.G. was partially funded by the Paul C. Zamecnik, MD, Chair in Oncology at Massachusetts General Hospital. G. G. and M.S.L. were partially funded by the NIH TCGA Genome Data Analysis Center (U24CA143845). M.S.L. was partially funded by the NHGRI Genome Sequencing Center (U54HG003067). E.S., K.R.C., and D.A.W. were partially funded by NHGRI grant (U54HG003273). N.J.H., P.P., Y.E.M., and A. Kamburov were funded by G.G.'s startup funds at MGH. NR 68 TC 22 Z9 22 U1 16 U2 40 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 28 PY 2016 VL 164 IS 3 BP 538 EP 549 DI 10.1016/j.cell.2015.12.050 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DC0KU UT WOS:000368906800022 PM 26806129 ER PT J AU Ceccarelli, M Barthel, FP Malta, TM Sabedot, TS Salama, SR Murray, BA Morozova, O Newton, Y Radenbaugh, A Pagnotta, SM Anjum, S Wang, JG Manyam, G Zoppoli, P Ling, S Rao, AA Grifford, M Cherniack, AD Zhang, HL Poisson, L Carlotti, CG Tirapelli, DPD Rao, A Mikkelsen, T Lau, CC Yung, WKA Rabadan, R Huse, J Brat, DJ Lehman, NL Barnholtz-Sloan, JS Zheng, S Hess, K Rao, G Meyerson, M Beroukhim, R Cooper, L Akbani, R Wrensch, M Haussler, D Aldape, KD Laird, PW Gutmann, DH Noushmehr, H Iavarone, A Verhaak, RGW AF Ceccarelli, Michele Barthel, Floris P. Malta, Tathiane M. Sabedot, Thais S. Salama, Sofie R. Murray, Bradley A. Morozova, Olena Newton, Yulia Radenbaugh, Amie Pagnotta, Stefano M. Anjum, Samreen Wang, Jiguang Manyam, Ganiraju Zoppoli, Pietro Ling, Shiyun Rao, Arjun A. Grifford, Mia Cherniack, Andrew D. Zhang, Hailei Poisson, Laila Carlotti, Carlos Gilberto, Jr. Tirapelli, Daniela Pretti da Cunha Rao, Arvind Mikkelsen, Tom Lau, Ching C. Yung, W. K. Alfred Rabadan, Raul Huse, Jason Brat, Daniel J. Lehman, Norman L. Barnholtz-Sloan, Jill S. Zheng, Siyuan Hess, Kenneth Rao, Ganesh Meyerson, Matthew Beroukhim, Rameen Cooper, Lee Akbani, Rehan Wrensch, Margaret Haussler, David Aldape, Kenneth D. Laird, Peter W. Gutmann, David H. Noushmehr, Houtan Iavarone, Antonio Verhaak, Roel G. W. CA TCGA Res Network TI Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma SO CELL LA English DT Article ID TERT PROMOTER MUTATIONS; PILOCYTIC ASTROCYTOMA; GENOMIC ANALYSIS; BRAIN-TUMORS; GRADE II; GLIOBLASTOMA; EXPRESSION; CANCER; CELLS; IDH1 AB Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. C1 [Ceccarelli, Michele; Anjum, Samreen] Hamad Bin Khalifa Univ, Qatar Comp Res Inst, POB 5825, Doha, Qatar. [Ceccarelli, Michele; Pagnotta, Stefano M.] Univ Sannio, Dept Sci & Technol, I-82100 Benevento, Italy. [Barthel, Floris P.; Manyam, Ganiraju; Ling, Shiyun; Rao, Arvind; Yung, W. K. Alfred; Zheng, Siyuan; Hess, Kenneth; Rao, Ganesh; Akbani, Rehan; Verhaak, Roel G. W.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Dept Bioinformat & Computat Biol,Dept Neurosurg, Dept Genom Med,Dept Biostat,Dept Neurooncol, Houston, TX 77030 USA. [Barthel, Floris P.] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Oncol Grad Sch Amsterdam, NL-1081 HV Amsterdam, Netherlands. [Malta, Tathiane M.; Sabedot, Thais S.; Carlotti, Carlos Gilberto, Jr.; Tirapelli, Daniela Pretti da Cunha; Noushmehr, Houtan] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Dept Genet CISBi NAP, BR-14049900 Ribeirao Preto, SP, Brazil. [Malta, Tathiane M.; Sabedot, Thais S.; Carlotti, Carlos Gilberto, Jr.; Tirapelli, Daniela Pretti da Cunha; Noushmehr, Houtan] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Integrat Syst Biol CISBi, NAP USP, BR-14049900 Ribeirao Preto, SP, Brazil. [Salama, Sofie R.; Morozova, Olena; Newton, Yulia; Radenbaugh, Amie; Rao, Arjun A.; Grifford, Mia; Haussler, David] Univ Calif Santa Cruz, Genom Inst, Santa Cruz, CA 95064 USA. [Murray, Bradley A.; Cherniack, Andrew D.; Zhang, Hailei; Meyerson, Matthew; Beroukhim, Rameen] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA. [Murray, Bradley A.; Cherniack, Andrew D.; Zhang, Hailei; Meyerson, Matthew; Beroukhim, Rameen] Harvard Univ, Cambridge, MA 02142 USA. [Pagnotta, Stefano M.] BIOGEM Ist Ric Genetiche G Salvatore, I-83031 Campo Reale, Ariano Irpino, Italy. [Wang, Jiguang; Zoppoli, Pietro; Rabadan, Raul; Iavarone, Antonio] Columbia Univ, Med Ctr, Dept Syst Biol & Biomed Informat, Dept Neurol,Dept Pathol,Inst Canc Genet, New York, NY 10032 USA. [Poisson, Laila; Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Lau, Ching C.] Childrens Hosp, Houston, TX 77030 USA. [Lau, Ching C.] Baylor Coll Med, Houston, TX 77030 USA. [Huse, Jason] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Brat, Daniel J.; Cooper, Lee] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Lehman, Norman L.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Meyerson, Matthew; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Wrensch, Margaret] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94158 USA. [Aldape, Kenneth D.] Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada. [Laird, Peter W.] Van Andel Res Inst, Grand Rapids, MI 49503 USA. [Gutmann, David H.] Washington Univ, Sch Med, St Louis, MO 63110 USA. RP Verhaak, RGW (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Pathol, Dept Bioinformat & Computat Biol,Dept Neurosurg, Dept Genom Med,Dept Biostat,Dept Neurooncol, Houston, TX 77030 USA.; Noushmehr, H (reprint author), Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Dept Genet CISBi NAP, BR-14049900 Ribeirao Preto, SP, Brazil.; Iavarone, A (reprint author), Columbia Univ, Med Ctr, Dept Syst Biol & Biomed Informat, Dept Neurol,Dept Pathol,Inst Canc Genet, New York, NY 10032 USA. EM houtan@usp.br; ai2102@columbia.edu; rverhaak@mdanderson.org RI Lehman, Norman/A-7351-2015; Manyam, Ganiraju/E-9150-2012; Carlotti, Carlos/C-1608-2012; Sarraf Sabedot, Thais/J-2349-2016; Malta, Tathiane/N-1686-2013; Marra, Marco/B-5987-2008; Miller, Ryan/B-9365-2008; Coetzee, Simon/C-1218-2014; OI PAGNOTTA, Stefano Maria/0000-0002-8298-9777; Rao, Arjun/0000-0003-4480-3190; Manyam, Ganiraju/0000-0001-6006-8961; Carlotti, Carlos/0000-0002-7055-0564; Malta, Tathiane/0000-0003-1129-5791; Miller, Ryan/0000-0002-0096-8762; Coetzee, Simon/0000-0003-4267-5930; Ceccarelli, Michele/0000-0002-4702-6617; Perou, Charles/0000-0001-9827-2247 FU NIH [U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U54HG003067, U54HG003079, U54HG003273]; Cancer Prevention & Research Institute of Texas (CPRIT) [R140606]; Sao Paulo Research Foundation (FAPESP) [2014/02245-3, 2015/07925-5, 2015/02844-7, 2015/08321-3]; Novartis; Bayer; [U24CA126543]; [U24CA126544]; [U24CA126546]; [U24CA126551]; [U24CA126554]; [U24CA126561]; [U24CA126563]; [U24CA143731]; [U24CA143843]; [P30CA016672]; [P50 CA127001]; [U54CA193313]; [R01CA179044]; [R01CA185486]; [R01 CA190121]; [P01 CA085878] FX This study was supported by NIH grants U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563, U24CA143731, U24CA143843, P30CA016672, P50 CA127001, U54CA193313, R01CA179044, R01CA185486, R01 CA190121, and P01 CA085878; Cancer Prevention & Research Institute of Texas (CPRIT) R140606; and Sao Paulo Research Foundation (FAPESP) 2014/02245-3, 2015/07925-5, 2015/02844-7, and 2015/08321-3. D.J.W. is a consultant for Zymo Research Corporation. R.B. is a consultant for and received grant funding from Novartis. A.D.C. and M.M. received grant support from Bayer. NR 41 TC 76 Z9 79 U1 19 U2 40 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 28 PY 2016 VL 164 IS 3 BP 550 EP 563 DI 10.1016/j.cell.2015.12.028 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DC0KU UT WOS:000368906800023 PM 26824661 ER PT J AU Zech, SG Kohlmann, A Zhou, TJ Li, F Squillace, RM Parillon, LE Greenfield, MT Miller, DP Qi, JW Thomas, RM Wang, YH Xu, YJ Miret, JJ Shakespeare, WC Zhu, XT Dalgarno, DC AF Zech, Stephan G. Kohlmann, Anna Zhou, Tianjun Li, Feng Squillace, Rachel M. Parillon, Lois E. Greenfield, Matthew T. Miller, David P. Qi, Jiwei Thomas, R. Mathew Wang, Yihan Xu, Yongjin Miret, Juan J. Shakespeare, William C. Zhu, Xiaotian Dalgarno, David C. TI Novel Small Molecule Inhibitors of Choline Kinase Identified by Fragment-Based Drug Discovery SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TARGET RESIDENCE TIME; MAGNETIC-RESONANCE-SPECTROSCOPY; TRANSFER DIFFERENCE NMR; ANTITUMOR STRATEGY; LEAD OPTIMIZATION; LIPID-METABOLISM; ALPHA; BINDING; CANCER; CELLS AB Choline kinase alpha (ChoK alpha) is an enzyme involved in the synthesis of phospholipids and thereby plays key roles in regulation of cell proliferation, oncogenic transformation, and human carcinogenesis. Since several inhibitors of ChoK alpha display antiproliferative activity in both cellular and animal models, this novel oncogene has recently gained interest as a promising small molecule target for cancer therapy. Here we summarize our efforts to further validate ChoK? as an oncogenic target and explore the activity of novel small molecule inhibitors of ChoK?. Starting from weakly binding fragments, we describe a structure based lead discovery approach, which resulted in novel highly potent inhibitors of ChoK alpha. In cancer cell lines, our lead compounds exhibit a dose-dependent decrease of phosphocholine, inhibition of cell growth, and induction of apoptosis at low micromolar concentrations. The druglike lead series presented here is optimizable for improvements in cellular potency, drug target residence time, and pharmacokinetic parameters. These inhibitors may be utilized not only to further validate ChoK alpha as antioncogenic target but also as novel chemical matter that may lead to antitumor agents that specifically interfere with cancer cell metabolism. C1 [Zech, Stephan G.; Kohlmann, Anna; Zhou, Tianjun; Li, Feng; Squillace, Rachel M.; Parillon, Lois E.; Greenfield, Matthew T.; Miller, David P.; Qi, Jiwei; Thomas, R. Mathew; Wang, Yihan; Xu, Yongjin; Miret, Juan J.; Shakespeare, William C.; Zhu, Xiaotian; Dalgarno, David C.] ARIAD Pharmaceut Inc, 26 Landsdowne St, Cambridge, MA 02139 USA. [Squillace, Rachel M.] Fdn Med, 150 Second St, Cambridge, MA 02141 USA. [Parillon, Lois E.] Siemens Healthcare Diagnost, 333 Coney St, Walpole, MA 02032 USA. [Miller, David P.] Vaxess Technol, 700 Main St, Cambridge, MA 02139 USA. [Thomas, R. Mathew] Cerulean Pharma Inc, 840 Mem Dr, Cambridge, MA 02139 USA. [Wang, Yihan] Boston Ibio Inc, 32 Leonard Ave, Newton, MA 02465 USA. [Miret, Juan J.] Dana Farber Canc Inst, Belfer Inst, 77 Louis Pasteur Ave, Boston, MA 02115 USA. RP Zech, SG (reprint author), ARIAD Pharmaceut Inc, 26 Landsdowne St, Cambridge, MA 02139 USA. EM Stephan.Zech@ariad.com NR 52 TC 5 Z9 5 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD JAN 28 PY 2016 VL 59 IS 2 BP 671 EP 686 DI 10.1021/acs.jmedchem.5b01552 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DC3JN UT WOS:000369115700013 PM 26700752 ER PT J AU Roberts, AW Davids, MS Pagel, JM Kahl, BS Puvvada, SD Gerecitano, JF Kipps, TJ Anderson, MA Brown, JR Gressick, L Wong, S Dunbar, M Zhu, M Desai, MB Cerri, E Enschede, SH Humerickhouse, RA Wierda, WG Seymour, JF AF Roberts, Andrew W. Davids, Matthew S. Pagel, John M. Kahl, Brad S. Puvvada, Soham D. Gerecitano, John F. Kipps, Thomas J. Anderson, Mary Ann Brown, Jennifer R. Gressick, Lori Wong, Shekman Dunbar, Martin Zhu, Ming Desai, Monali B. Cerri, Elisa Enschede, Sari Heitner Humerickhouse, Rod A. Wierda, William G. Seymour, John F. TI Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID KINASE INHIBITOR IBRUTINIB; INTERNATIONAL WORKSHOP; ANTITUMOR-ACTIVITY; DOSE-ESCALATION; PHASE-I; RITUXIMAB; FLUDARABINE; CYCLOPHOSPHAMIDE; CHEMOIMMUNOTHERAPY; APOPTOSIS AB BACKGROUND New treatments have improved outcomes for patients with relapsed chronic lymphocytic leukemia (CLL), but complete remissions remain uncommon. Venetoclax has a distinct mechanism of action; it targets BCL2, a protein central to the survival of CLL cells. METHODS We conducted a phase 1 dose-escalation study of daily oral venetoclax in patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL) to assess safety, pharmacokinetic profile, and efficacy. In the dose-escalation phase, 56 patients received active treatment in one of eight dose groups that ranged from 150 to 1200 mg per day. In an expansion cohort, 60 additional patients were treated with a weekly stepwise ramp-up in doses as high as 400 mg per day. RESULTS The majority of the study patients had received multiple previous treatments, and 89% had poor prognostic clinical or genetic features. Venetoclax was active at all dose levels. Clinical tumor lysis syndrome occurred in 3 of 56 patients in the dose-escalation cohort, with one death. After adjustments to the dose-escalation schedule, clinical tumor lysis syndrome did not occur in any of the 60 patients in the expansion cohort. Other toxic effects included mild diarrhea (in 52% of the patients), upper respiratory tract infection (in 48%), nausea (in 47%), and grade 3 or 4 neutropenia (in 41%). A maximum tolerated dose was not identified. Among the 116 patients who received venetoclax, 92 (79%) had a response. Response rates ranged from 71 to 79% among patients in subgroups with an adverse prognosis, including those with resistance to fludarabine, those with chromosome 17p deletions (deletion 17p CLL), and those with unmutated IGHV. Complete remissions occurred in 20% of the patients, including 5% who had no minimal residual disease on flow cytometry. The 15-month progression-free survival estimate for the 400-mg dose groups was 69%. CONCLUSIONS Selective targeting of BCL2 with venetoclax had a manageable safety profile and induced substantial responses in patients with relapsed CLL or SLL, including those with poor prognostic features. C1 [Roberts, Andrew W.; Anderson, Mary Ann] Royal Melbourne Hosp, Dept Clin Haematol, Parkville, Vic 3050, Australia. [Roberts, Andrew W.; Anderson, Mary Ann] Royal Melbourne Hosp, Bone Marrow Transplantat Unit, Parkville, Vic 3050, Australia. [Roberts, Andrew W.; Anderson, Mary Ann] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Canc & Haematol, Parkville, Vic 3050, Australia. [Roberts, Andrew W.; Seymour, John F.] Victorian Comprehens Canc Ctr, Parkville, Vic, Australia. [Roberts, Andrew W.; Seymour, John F.] Univ Melbourne, Melbourne, Vic, Australia. [Seymour, John F.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Davids, Matthew S.; Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pagel, John M.] Swedish Med Ctr, Seattle, WA USA. [Kahl, Brad S.] Washington Univ, St Louis, MO 63130 USA. [Puvvada, Soham D.] Univ Arizona, Tucson, AZ USA. [Gerecitano, John F.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Gerecitano, John F.] Weill Cornell Med Coll, New York, NY USA. [Kipps, Thomas J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Gressick, Lori; Wong, Shekman; Dunbar, Martin; Zhu, Ming; Desai, Monali B.; Cerri, Elisa; Enschede, Sari Heitner; Humerickhouse, Rod A.] AbbVie, N Chicago, IL USA. [Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Roberts, AW (reprint author), Royal Melbourne Hosp, Melbourne, Vic 3050, Australia. EM andrew.roberts@mh.org.au FU AbbVie; Genentech FX Funded by AbbVie and Genentech; ClinicalTrials.gov number, NCT01328626. NR 37 TC 151 Z9 152 U1 29 U2 54 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 28 PY 2016 VL 374 IS 4 BP 311 EP 322 DI 10.1056/NEJMoa1513257 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA DB8IJ UT WOS:000368760100005 PM 26639348 ER PT J AU Byrd, JC Harrington, B O'Brien, S Jones, JA Schuh, A Devereux, S Chaves, J Wierda, WG Awan, FT Brown, JR Hillmen, P Stephens, DM Ghia, P Barrientos, JC Pagel, JM Woyach, J Johnson, D Huang, J Wang, X Kaptein, A Lannutti, BJ Covey, T Fardis, M McGreivy, J Hamdy, A Rothbaum, W Izumi, R Diacovo, TG Johnson, AJ Furman, RR AF Byrd, John C. Harrington, Bonnie O'Brien, Susan Jones, Jeffrey A. Schuh, Anna Devereux, Steve Chaves, Jorge Wierda, William G. Awan, Farrukh T. Brown, Jennifer R. Hillmen, Peter Stephens, Deborah M. Ghia, Paolo Barrientos, Jacqueline C. Pagel, John M. Woyach, Jennifer Johnson, Dave Huang, Jane Wang, Xiaolin Kaptein, Allard Lannutti, Brian J. Covey, Todd Fardis, Maria McGreivy, Jesse Hamdy, Ahmed Rothbaum, Wayne Izumi, Raquel Diacovo, Thomas G. Johnson, Amy J. Furman, Richard R. TI Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TYROSINE KINASE INHIBITOR; B-CELL RECEPTOR; X-LINKED AGAMMAGLOBULINEMIA; OPEN-LABEL; IN-VIVO; IBRUTINIB; BTK; PCI-32765; ACTIVATION; LYMPHOMA AB BACKGROUND Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors. METHODS In this uncontrolled, phase 1-2, multicenter study, we administered oral acalabrutinib to 61 patients who had relapsed CLL to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib. Patients were treated with acalabrutinib at a dose of 100 to 400 mg once daily in the dose-escalation (phase 1) portion of the study and 100 mg twice daily in the expansion (phase 2) portion. RESULTS The median age of the patients was 62 years, and patients had received a median of three previous therapies for CLL; 31% had chromosome 17p13.1 deletion, and 75% had unmutated immunoglobulin heavy-chain variable genes. No dose-limiting toxic effects occurred during the dose-escalation portion of the study. The most common adverse events observed were headache (in 43% of the patients), diarrhea (in 39%), and increased weight (in 26%). Most adverse events were of grade 1 or 2. At a median follow-up of 14.3 months, the overall response rate was 95%, including 85% with a partial response and 10% with a partial response with lymphocytosis; the remaining 5% of patients had stable disease. Among patients with chromosome 17p13.1 deletion, the overall response rate was 100%. No cases of Richter's transformation (CLL that has evolved into large-cell lymphoma) and only one case of CLL progression have occurred. CONCLUSIONS In this study, the selective BTK inhibitor acalabrutinib had promising safety and efficacy profiles in patients with relapsed CLL, including those with chromosome 17p13.1 deletion. C1 [Byrd, John C.; Jones, Jeffrey A.; Awan, Farrukh T.; Woyach, Jennifer; Johnson, Amy J.] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Harrington, Bonnie] Coll Vet Med, Dept Vet Biosci, Columbus, OH USA. [O'Brien, Susan] Univ Calif Irvine, UC Irvine Hlth Chao Family Comprehens Canc Ctr, Orange, CA USA. [Schuh, Anna] Univ Oxford, Oxford, England. [Devereux, Steve] Kings Coll Hosp London, NHS Fdn Trust, London, England. [Hillmen, Peter] St James Univ Hosp, Dept Haematol, Leeds, W Yorkshire, England. [Chaves, Jorge] Northwest Med Specialties, Tacoma, WA USA. [Pagel, John M.] Swedish Canc Inst, Seattle, WA USA. [Wierda, William G.] Univ Texas Houston, Div Canc Med, Dept Leukemia, Houston, TX USA. [Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stephens, Deborah M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Ghia, Paolo] Univ Vita Salute San Raffaele, Milan, Italy. [Ghia, Paolo] Ist Sci San Raffaele, Milan, Italy. [Barrientos, Jacqueline C.] Hofstra North Shore LIJ Sch Med, Chron Lymphocyt Leukemia Res & Treatment Ctr, Lake Success, NY USA. [Diacovo, Thomas G.] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY USA. [Furman, Richard R.] Weill Cornell Med Ctr, New York Presbyterian, New York, NY USA. [Johnson, Dave; Huang, Jane; Wang, Xiaolin; Kaptein, Allard; Lannutti, Brian J.; Covey, Todd; Fardis, Maria; McGreivy, Jesse; Hamdy, Ahmed; Rothbaum, Wayne; Izumi, Raquel] Acerta Pharma, Oss, Netherlands. RP Byrd, JC (reprint author), B302 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM john.byrd@osumc.edu RI Woyach, Jennifer/F-1087-2015; Jones, Jeffrey/E-3321-2011; Ghia, Paolo/K-7138-2016; Awan, Farrukh/L-5642-2016; Devereux, Stephen/B-4766-2009; OI Ghia, Paolo/0000-0003-3750-7342; Awan, Farrukh/0000-0003-1813-9812; Devereux, Stephen/0000-0002-8046-0386; Stephens, Deborah/0000-0001-9188-5008 FU Acerta Pharma FX Funded by the Acerta Pharma and others; ClinicalTrials.gov number, NCT02029443. NR 32 TC 68 Z9 69 U1 7 U2 14 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 28 PY 2016 VL 374 IS 4 BP 323 EP 332 DI 10.1056/NEJMoa1509981 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DB8IJ UT WOS:000368760100006 PM 26641137 ER PT J AU Goldstein, D Moskowitz, AJ Gelijns, AC Ailawadi, G Parides, MK Perrault, LP Hung, JW Voisine, P Dagenais, F Gillinov, AM Thourani, V Argenziano, M Gammie, JS Mack, M Demers, P Atluri, P Rose, EA O'Sullivan, K Williams, DL Bagiella, E Michler, RE Weisel, RD Miller, MA Geller, NL Taddei-Peters, WC Smith, PK Moquete, E Overbey, JR Kron, IL O'Gara, PT Acker, MA AF Goldstein, D. Moskowitz, A. J. Gelijns, A. C. Ailawadi, G. Parides, M. K. Perrault, L. P. Hung, J. W. Voisine, P. Dagenais, F. Gillinov, A. M. Thourani, V. Argenziano, M. Gammie, J. S. Mack, M. Demers, P. Atluri, P. Rose, E. A. O'Sullivan, K. Williams, D. L. Bagiella, E. Michler, R. E. Weisel, R. D. Miller, M. A. Geller, N. L. Taddei-Peters, W. C. Smith, P. K. Moquete, E. Overbey, J. R. Kron, I. L. O'Gara, P. T. Acker, M. A. CA CTSN TI Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEART-FAILURE; VALVE ANNULOPLASTY; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; RING ANNULOPLASTY; REPAIR; REPLACEMENT; PREDICTORS; RECURRENCE; MECHANISM AB BACKGROUND In a randomized trial comparing mitral-valve repair with mitral-valve replacement in patients with severe ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI), survival, or adverse events at 1 year after surgery. However, patients in the repair group had significantly more recurrences of moderate or severe mitral regurgitation. We now report the 2-year outcomes of this trial. METHODS We randomly assigned 251 patients to mitral-valve repair or replacement. Patients were followed for 2 years, and clinical and echocardiographic outcomes were assessed. RESULTS Among surviving patients, the mean (+/- SD) 2-year LVESVI was 52.6 +/- 27.7 ml per square meter of body-surface area with mitral-valve repair and 60.6 +/- 39.0 ml per square meter with mitral-valve replacement (mean changes from baseline, -9.0 ml per square meter and -6.5 ml per square meter, respectively). Two-year mortality was 19.0% in the repair group and 23.2% in the replacement group (hazard ratio in the repair group, 0.79; 95% confidence interval, 0.46 to 1.35; P=0.39). The rank-based assessment of LVESVI at 2 years (incorporating deaths) showed no significant between-group difference (z score = -1.32, P=0.19). The rate of recurrence of moderate or severe mitral regurgitation over 2 years was higher in the repair group than in the replacement group (58.8% vs. 3.8%, P < 0.001). There were no significant between-group differences in rates of serious adverse events and overall readmissions, but patients in the repair group had more serious adverse events related to heart failure (P=0.05) and cardiovascular readmissions (P=0.01). On the Minnesota Living with Heart Failure questionnaire, there was a trend toward greater improvement in the replacement group (P=0.07). CONCLUSIONS In patients undergoing mitral-valve repair or replacement for severe ischemic mitral regurgitation, we observed no significant between-group difference in left ventricular reverse remodeling or survival at 2 years. Mitral regurgitation recurred more frequently in the repair group, resulting in more heart-failure-related adverse events and cardiovascular admissions. C1 [Goldstein, D.; Michler, R. E.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Cardiothorac Surg, New York, NY USA. [Moskowitz, A. J.; Gelijns, A. C.; Parides, M. K.; O'Sullivan, K.; Williams, D. L.; Bagiella, E.; Moquete, E.; Overbey, J. R.] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, Int Ctr Hlth Outcomes & Innovat Res, New York, NY 10029 USA. [Rose, E. A.] Icahn Sch Med Mt Sinai, Cardiovasc Inst, New York, NY USA. [Argenziano, M.] Columbia Univ, Coll Phys & Surg, Dept Surg, Div Cardiothorac Surg, New York, NY USA. [Ailawadi, G.; Kron, I. L.] Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA. [Perrault, L. P.; Demers, P.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Voisine, P.; Dagenais, F.] Inst Univ Cardiol Quebec, Hop Laval, Quebec City, PQ, Canada. [Weisel, R. D.] Univ Toronto, Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Weisel, R. D.] Univ Toronto, Div Cardiovasc Surg, Toronto Gen Hosp, Univ Hlth Network, Toronto, ON, Canada. [Weisel, R. D.] Univ Toronto, Div Cardiac Surg, Toronto, ON, Canada. [Hung, J. W.] Massachusetts Gen Hosp, Echocardiog Core Lab, Boston, MA 02114 USA. [O'Gara, P. T.] Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. [Gillinov, A. M.] Cleveland Clin Fdn, Dept Thorac & Cardiovasc Surg, Cleveland, OH USA. [Thourani, V.] Emory Univ, Sch Med, Div Cardiothorac Surg, Clin Res Unit, Atlanta, GA 30322 USA. [Gammie, J. S.] Univ Maryland, Baltimore, MD 21201 USA. [Miller, M. A.; Taddei-Peters, W. C.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA. [Geller, N. L.] NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA. [Mack, M.] Baylor Res Inst, Dallas, TX USA. [Atluri, P.; Acker, M. A.] Univ Penn, Sch Med, Div Cardiovasc Surg, Dept Surg, Philadelphia, PA 19104 USA. [Smith, P. K.] Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA. RP Gelijns, AC (reprint author), Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA. EM annetine.gelijns@mssm.edu OI Moskowitz, Alan/0000-0002-4412-9450; Browndyke, Jeffrey/0000-0002-8573-7073 FU National Institutes of Health and Canadian Institutes of Health Research FX Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00807040. NR 43 TC 49 Z9 50 U1 1 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 28 PY 2016 VL 374 IS 4 BP 344 EP 353 DI 10.1056/NEJMoa1512913 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DB8IJ UT WOS:000368760100008 PM 26550689 ER PT J AU Heher, E Markmann, JF AF Heher, Eliot Markmann, James F. TI The Clearer BENEFITS of Belatacept SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CALCINEURIN INHIBITORS; RENAL-TRANSPLANTATION; CELLS C1 [Heher, Eliot] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Markmann, James F.] Massachusetts Gen Hosp, Div Abdominal Transplant Surg, Boston, MA 02114 USA. [Heher, Eliot; Markmann, James F.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. RP Heher, E (reprint author), Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.; Heher, E (reprint author), Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 28 PY 2016 VL 374 IS 4 BP 388 EP 389 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DB8IJ UT WOS:000368760100016 PM 26816017 ER PT J AU Kleinstiver, BP Pattanayak, V Prew, MS Tsai, SQ Nguyen, NT Zheng, ZL Joung, JK AF Kleinstiver, Benjamin P. Pattanayak, Vikram Prew, Michelle S. Tsai, Shengdar Q. Nguyen, Nhu T. Zheng, Zongli Joung, J. Keith TI High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects SO NATURE LA English DT Article ID RNA-GUIDED ENDONUCLEASES; CAS SYSTEMS; ENGINEERED NUCLEASES; CRISPR/CAS9 SYSTEMS; DNA RECOGNITION; HUMAN-CELLS; DUAL-RNA; SPECIFICITY; CLEAVAGE; TALENS AB CRISPR-Cas9 nucleases are widely used for genome editing but can induce unwanted off-target mutations. Existing strategies for reducing genome-wide off-target effects of the widely used Streptococcus pyogenes Cas9 (SpCas9) are imperfect, possessing only partial or unproven efficacies and other limitations that constrain their use. Here we describe SpCas9-HF1, a high-fidelity variant harbouring alterations designed to reduce non-specific DNA contacts. SpCas9-HF1 retains on-target activities comparable to wild-type SpCas9 with > 85% of single-guide RNAs (sgRNAs) tested in human cells. Notably, with sgRNAs targeted to standard non-repetitive sequences, SpCas9-HF1 rendered all or nearly all off-target events undetectable by genome-wide break capture and targeted sequencing methods. Even for atypical, repetitive target sites, the vast majority of off-target mutations induced by wild-type SpCas9 were not detected with SpCas9-HF1. With its exceptional precision, SpCas9-HF1 provides an alternative to wild-type SpCas9 for research and therapeutic applications. More broadly, our results suggest a general strategy for optimizing genome-wide specificities of other CRISPR-RNA-guided nucleases. C1 [Kleinstiver, Benjamin P.; Pattanayak, Vikram; Prew, Michelle S.; Tsai, Shengdar Q.; Nguyen, Nhu T.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA. [Kleinstiver, Benjamin P.; Pattanayak, Vikram; Prew, Michelle S.; Tsai, Shengdar Q.; Nguyen, Nhu T.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Kleinstiver, Benjamin P.; Pattanayak, Vikram; Tsai, Shengdar Q.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Zheng, Zongli] City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Hong Kong, Peoples R China. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA.; Joung, JK (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA.; Joung, JK (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM jjoung@mgh.harvard.edu RI Zheng, Zongli/B-2917-2011 OI Zheng, Zongli/0000-0003-4849-4903 FU Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship; Massachusetts General Hospital (MGH) Department of Pathology; MGH Tosteson; Fund for Medical Discovery Fellowship; US National Institutes of Health (NIH) Director's Pioneer Award [DP1 GM105378]; NIH [R01 GM107427, R01 GM088040]; Jim and Ann Orr MGH Research Scholar Award FX B.P.K. is supported by a Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship. V.P. was supported by the Massachusetts General Hospital (MGH) Department of Pathology. S.Q.T. is supported by an MGH Tosteson and Fund for Medical Discovery Fellowship. J.K.J. is supported by a US National Institutes of Health (NIH) Director's Pioneer Award (DP1 GM105378), NIH R01 GM107427, NIH R01 GM088040, and the Jim and Ann Orr MGH Research Scholar Award. NR 45 TC 197 Z9 205 U1 69 U2 201 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 28 PY 2016 VL 529 IS 7587 BP 490 EP + DI 10.1038/nature16526 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB7DD UT WOS:000368673800029 PM 26735016 ER PT J AU Guglietta, PM Moran, CJ Ryan, DP Sagar, P Huck, AE AF Guglietta, Patricia M. Moran, Christopher J. Ryan, Daniel P. Sagar, Pallavi Huck, Amelia E. TI Case 3-2016: A 9-Year-Old Girl with Intermittent Abdominal Pain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HELICOBACTER-PYLORI INFECTION; INTESTINAL MALROTATION; CELIAC-DISEASE; CHILDREN; SPLEEN; RECOMMENDATIONS; ESOPHAGITIS; GUIDELINES; SYMPTOMS; NASPGHAN C1 [Guglietta, Patricia M.; Moran, Christopher J.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Ryan, Daniel P.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Sagar, Pallavi] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Huck, Amelia E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Guglietta, Patricia M.; Moran, Christopher J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ryan, Daniel P.] Harvard Univ, Sch Med, Dept Pediat Surg, Boston, MA 02115 USA. [Sagar, Pallavi] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Huck, Amelia E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Guglietta, PM (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. FU Janssen Scientific; Actavis Labs FX Dr. Moran reports receiving consulting fees from Janssen Scientific and grant support through his institution from Actavis Labs. No other potential conflict of interest relevant to this article was reported. NR 24 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 28 PY 2016 VL 374 IS 4 BP 373 EP 382 DI 10.1056/NEJMcpc1413305 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DB8IJ UT WOS:000368760100013 PM 26816015 ER PT J AU Yu, L Morishima, C Ioannou, GN AF Yu, Lei Morishima, Chihiro Ioannou, George N. TI Sex difference in liver-related mortality and transplantation associated with dietary cholesterol in chronic hepatitis C virus infection SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Diets; Cholesterol; Cirrhosis; Sex differences; Hepatitis C virus ID LONG-TERM TREATMENT; TOTAL-ENERGY INTAKE; DISEASE PROGRESSION; FIBROSIS PROGRESSION; CIRRHOSIS TRIAL; UNITED-STATES; GENOTYPE 1; THERAPY; INTERFERON; MODEL AB Dietary cholesterol induces hepatic inflammation and fibrosis in animals. We aimed to determine whether dietary cholesterol affects liver-related mortality in hepatitis C virus (HCV)-infected patients. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial. The study included HCV patients with advanced fibrosis and compensated cirrhosis. The analysis included 657 patients who completed two FFQ. We assessed whether cholesterol intake, measured in mg/4184 kJ (mg/1000 kcal) of energy intake, was associated with liver-related death or transplantation. In 4.7 (SD 1.6) years, the incidence of liver-related death (n 46) or transplantation (n 52) was 31.8/1000 person-years. The relationship between cholesterol intake and liver-related death or transplantation was significantly different between men and women (test for interaction, P value = 0.01). Each higher quartile of cholesterol intake was associated with an increased risk for liver-related death or transplantation in women (adjusted hazard ratio (AHR) 1.83; 95 % CI 1.12, 2.99; P-trend= 0.02), but not in men (AHR 0.96; 95 % CI 0.76, 1.22; P-trend = 0.73). Compared with women whose cholesterol intake was within the recommended guidelines (300 mg/d with a 8368 kJ (2000 kcal) diet), women who consumed more cholesterol had significantly increased risk for liver-related death or transplantation (AHR 4.04; 95 % CI 1.42, 11.5). High dietary cholesterol was associated with an increased risk for liver-related death and transplantation in HCV-infected women with advanced fibrosis or compensated cirrhosis. Future studies should assess whether reducing cholesterol intake, among women who consume an excessive amount, can decrease HCV-related mortality. C1 [Yu, Lei; Ioannou, George N.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Morishima, Chihiro] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Yu, L (reprint author), Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. EM leiy@medicine.washington.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Research Enhancement Award Program, Office of Research and Development, Veterans Affairs United States FX The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial was conducted by the HALT-C investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data from the HALT-C Trial reported here was supplied by the NIDDK Central Repository. This manuscript does not necessarily reflect the opinions or views of the HALT-C study, the NIDDK Central Repository or the NIDDK. G. N. I. is supported by Research Enhancement Award Program, Office of Research and Development, Veterans Affairs United States. NR 38 TC 0 Z9 1 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 EI 1475-2662 J9 BRIT J NUTR JI Br. J. Nutr. PD JAN 28 PY 2016 VL 115 IS 2 BP 193 EP 201 DI 10.1017/S0007114515004158 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CZ6UJ UT WOS:000367236200001 PM 26541123 ER PT J AU Gouse, H Magidson, JF Burnhams, W Remmert, JE Myers, B Joska, JA Carrico, AW AF Gouse, Hetta Magidson, Jessica F. Burnhams, Warren Remmert, Jocelyn E. Myers, Bronwyn Joska, John A. Carrico, Adam W. TI Implementation of Cognitive-Behavioral Substance Abuse Treatment in Sub-Saharan Africa: Treatment Engagement and Abstinence at Treatment Exit SO PLOS ONE LA English DT Article ID CONTINGENCY MANAGEMENT; MATRIX MODEL; SOUTH-AFRICA; CAPE-TOWN; METAANALYSIS; ALCOHOL; ACCESS AB Aims This study documented the treatment cascade for engagement in care and abstinence at treatment exit as well as examined correlates of these outcomes for the first certified Matrix Model (R) substance abuse treatment site in Sub-Saharan Africa. Design This retrospective chart review conducted at a resource-limited community clinic in Cape Town, South Africa, assessed treatment readiness and substance use severity at treatment entry as correlates of the number of sessions attended and biologically confirmed abstinence at treatment exit among 986 clients who initiated treatment from 2009-2014. Socio-demographic and clinical correlates of treatment outcomes were examined using logistic regression, modeling treatment completion and abstinence at treatment exit separately. Results Of the 2,233 clients who completed screening, approximately 44% (n = 986) initiated treatment. Among those who initiated treatment, 45% completed at least four group sessions, 30% completed early recovery skills training (i.e., at least eight group sessions), and 13% completed the full 16-week program. Approximately half (54%) of clients who provided a urine sample had negative urine toxicology results for any substance at treatment exit. Higher motivation at treatment entry was independently associated with greater odds of treatment completion and negative urine toxicology results at treatment exit. Conclusions Findings provide initial support for the successful implementation the Matrix Model in a resource-limited setting. Motivational enhancement interventions could support treatment initiation, promote sustained engagement in treatment, and achieve better treatment outcomes. C1 [Gouse, Hetta; Joska, John A.] HIV Mental Hlth Res Unit, Dept Psychiat & Mental Hlth, Cape Town, South Africa. [Magidson, Jessica F.; Remmert, Jocelyn E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Magidson, Jessica F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Burnhams, Warren] City Cape Town Hlth, Subst Abuse, Cape Town, South Africa. [Myers, Bronwyn] South African Med Res Council, Alcohol Tobacco & Other Drug Res Unit, Cape Town, South Africa. [Carrico, Adam W.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. RP Gouse, H (reprint author), HIV Mental Hlth Res Unit, Dept Psychiat & Mental Hlth, Cape Town, South Africa. EM hetta.gouse@uct.ac.za FU NIDA NIH HHS [K23 DA041901]; NIMH NIH HHS [T32 MH093310] NR 23 TC 1 Z9 1 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 27 PY 2016 VL 11 IS 1 AR e0147900 DI 10.1371/journal.pone.0147900 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC9GD UT WOS:000369528200062 PM 26816208 ER PT J AU Widger, K Friedrichsdorf, S Wolfe, J Liben, S Pole, JD Bouffet, E Greenberg, M Husain, A Siden, H Whitlock, JA Rapoport, A AF Widger, Kimberley Friedrichsdorf, Stefan Wolfe, Joanne Liben, Stephen Pole, Jason D. Bouffet, Eric Greenberg, Mark Husain, Amna Siden, Harold Whitlock, James A. Rapoport, Adam TI Protocol: Evaluating the impact of a nationwide train-the-trainer educational initiative to enhance the quality of palliative care for children with cancer SO BMC PALLIATIVE CARE LA English DT Article DE Pediatrics; Palliative care; Cancer; Quality care; Education; Knowledge translation ID OF-LIFE CARE; SYMPTOM ASSESSMENT; PARENTS; END; SUPPORT; DEATH; SCALE AB Background: There are identified gaps in the care provided to children with cancer based on the self-identified lack of education for health care professionals in pediatric palliative care and in the perceptions of bereaved parents who describe suboptimal care. In order to address these gaps, we will implement and evaluate a national roll-out of Education in Palliative and End-of-Life Care for Pediatrics (EPEC (R)-Pediatrics), using a 'Train-the-Trainer' model. Methods/design: In this study we are using a pre-post-test design and an integrated knowledge translation approach to assess the impact of the educational roll-out in four areas: 1) self-assessed knowledge of health professionals; 2) knowledge dissemination outcomes; 3) practice change outcomes; and 4) quality of palliative care. The quality of palliative care will be assessed using data from three sources: a) parent and child surveys about symptoms, quality of life and care provided; b) health record reviews of deceased patients; and c) bereaved parent surveys about end-of-life and bereavement care. After being trained in EPEC (R)-Pediatrics, 'Master Facilitators' will train 'Regional Teams' affiliated with 16 pediatric oncology programs in Canada. Each team will consist of three to five health professionals representing oncology, palliative care, and the community. Each team member will complete online modules and attend one of two face-to-face conferences, where they will receive training and materials to teach the EPEC (R)-Pediatrics curriculum to 'End-Users' in their region. Regional Teams will also choose a Tailored Implementation of Practice Standards (TIPS) Kit to guide implementation of a quality improvement project in their region; support will be provided via quarterly meetings with Co-Leads and via a listserv and webinars with other teams. Discussion: Through this study we aim to raise the level of pediatric palliative care education amongst health care professionals in Canada. Our study will be a significant step forward in evaluation of the impact of EPEC (R)-Pediatrics both on dissemination outcomes and on care quality at a national level. Based on the anticipated success of our project we hope to expand the EPEC (R)-Pediatrics roll-out to health professionals who care for children with non-oncological life-threatening conditions. C1 [Widger, Kimberley] Univ Toronto, Lawrence S Bloomberg Fac Nursing, 130-155 Coll St, Toronto, ON M5T 1P8, Canada. [Widger, Kimberley; Rapoport, Adam] Hosp Sick Children, Pediat Adv Care Team, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. [Friedrichsdorf, Stefan] Childrens Hosp & Clin Minnesota, Dept Pain Med Palliat Care & Integrat Med, 2525 Chicago Ave South, Minneapolis, MN 55404 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Pediat Palliat Care Serv, 450 Brookline Ave, Boston, MA 02215 USA. [Liben, Stephen] McGill Univ, Montreal Childrens Hosp, Pediat Palliat Care Program, 2300 Rue Tupper, Montreal, PQ H3H 1P3, Canada. [Pole, Jason D.] Pediat Oncol Grp Ontario, 480 Univ Ave,Suite 1014, Toronto, ON M5G 1V2, Canada. [Bouffet, Eric] Hosp Sick Children, Brain Tumor Program, Div Hematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. [Greenberg, Mark] Pediat Oncol Grp Ontario, Policy & Clin Affairs, 480 Univ Ave,Suite 1014, Toronto, ON M5G 1V2, Canada. [Husain, Amna] Univ Toronto, Dept Family & Community Med, Temmy Latner Ctr Palliat Care, Mt Sinai Hosp, 60 Murray St,4th Floor, Toronto, ON M5T 3L9, Canada. [Siden, Harold] Univ British Columbia, Canuck Pl Childrens Hosp, 1690 Matthews Ave, Vancouver, BC V6J 2T2, Canada. [Siden, Harold] Univ British Columbia, Dept Pediat, 1690 Matthews Ave, Vancouver, BC V6J 2T2, Canada. [Whitlock, James A.] Hosp Sick Children, Dept Hematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RP Widger, K (reprint author), Univ Toronto, Lawrence S Bloomberg Fac Nursing, 130-155 Coll St, Toronto, ON M5T 1P8, Canada.; Widger, K (reprint author), Hosp Sick Children, Pediat Adv Care Team, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM kim.widger@utoronto.ca OI Widger, Kimberley /0000-0001-8132-061X FU Canadian Partnership Against Cancer; Career Development Award from the Canadian Child Health Clinician Scientist Program; National Institutes of Health (NIH) [1R25CA151000-01] FX This project is funded by the Canadian Partnership Against Cancer. KW is supported by a Career Development Award from the Canadian Child Health Clinician Scientist Program. The development and initial implementation of EPEC (R)-Pediatrics is funded by the National Institutes of Health (NIH) (Grant #1R25CA151000-01). We wish to thank our Project Manager, Michelle Goertzen, and our Research Fellows, Drs. Jacqui Duc and Kelly Johnston, for their assistance in preparing this manuscript, creating data collection forms in REDCap (TM) and preparing ethics applications. NR 34 TC 1 Z9 1 U1 3 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-684X J9 BMC PALLIAT CARE JI BMC Palliat. Care PD JAN 27 PY 2016 VL 15 AR 12 DI 10.1186/s12904-016-0085-8 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DC1ML UT WOS:000368980300001 PM 26818836 ER PT J AU Diamandis, P Ferrer-Luna, R Huang, RY Folkerth, RD Ligon, AH Wen, PY Beroukhim, R Ligon, KL Ramkissoon, SH AF Diamandis, Phedias Ferrer-Luna, Ruben Huang, Raymond Y. Folkerth, Rebecca D. Ligon, Azra H. Wen, Patrick Y. Beroukhim, Rameen Ligon, Keith L. Ramkissoon, Shakti H. TI Case Report: Next generation sequencing identifies a NAB2-STAT6 fusion in Glioblastoma SO DIAGNOSTIC PATHOLOGY LA English DT Article DE NAB2-STAT6; Glioblastoma; Next generation sequencing ID COPY NUMBER; GLIOMAS; TEMOZOLOMIDE; LANDSCAPE; NEOPLASMS; TUMOR AB Background: Molecular profiling has uncovered genetic subtypes of glioblastoma (GBM), including tumors with IDH1 mutations that confer increase survival and improved response to standard-of-care therapies. By mapping the genetic landscape of brain tumors in routine clinical practice, we enable rapid identification of targetable genetic alterations. Case Presentation: A 29-year-old male presented with new onset seizures prompting neuroimaging studies, which revealed an enhancing 5 cm intra-axial lesion involving the right parietal lobe. He underwent a subtotal resection and pathologic examination revealed glioblastoma with mitoses, microvascular proliferation and necrosis. Immunohistochemical (IHC) analysis showed diffuse expression of GFAP, OLIG2 and SOX2 consistent with a tumor of glial lineage. Tumor cells were positive for IDH1(R132H) and negative for ATRX. Clinical targeted-exome sequencing (DFBWCC Oncopanel) identified multiple functional variants including IDH1 (p.R132H), TP53 (p.Y126_splice), ATRX (p.R1302fs*), HNF1A (p.R263H) and NF1 (p.H2592del) variants and a NAB2-STAT6 gene fusion event involving NAB2 exon 3 and STAT6 exon 18. Array comparative genomic hybridization (aCGH) further revealed a focal amplification of NAB2 and STAT6. IHC analysis demonstrated strong heterogenous STAT6 nuclear localization (in 20 % of tumor cells). Conclusions: While NAB2:STAT6 fusions are common in solitary fibrous tumors (SFT), we report this event for the first time in a newly diagnosed, secondary-type GBM or any other non-SFT. Our study further highlights the value of comprehensive genomic analyses in identifying patient-specific targetable mutations and rearrangements. C1 [Diamandis, Phedias] Univ Toronto, Dept Lab Med & Pathobiol, Neuropathol Program, 27 Kings Coll Circle, Toronto, ON M5S, Canada. [Diamandis, Phedias; Folkerth, Rebecca D.; Ligon, Azra H.; Ligon, Keith L.; Ramkissoon, Shakti H.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Ferrer-Luna, Ruben; Beroukhim, Rameen; Ligon, Keith L.] Broad Inst MIT & Harvard, Canc Program, 415 Main St, Cambridge, MA 02142 USA. [Ferrer-Luna, Ruben; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02115 USA. [Huang, Raymond Y.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Folkerth, Rebecca D.; Ligon, Azra H.; Ligon, Keith L.; Ramkissoon, Shakti H.] Harvard Univ, Sch Med, Dept Pathol, 25 Shattuck St, Boston, MA 02115 USA. [Folkerth, Rebecca D.; Ligon, Keith L.; Ramkissoon, Shakti H.] Boston Childrens Hosp, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA. [Wen, Patrick Y.; Ligon, Keith L.; Ramkissoon, Shakti H.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. RP Ramkissoon, SH (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.; Ramkissoon, SH (reprint author), Harvard Univ, Sch Med, Dept Pathol, 25 Shattuck St, Boston, MA 02115 USA.; Ramkissoon, SH (reprint author), Boston Childrens Hosp, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA.; Ramkissoon, SH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM sramkissoon@partners.org OI Diamandis, Phedias/0000-0001-5291-9068 FU NINDS NIH HHS [K08 NS087118] NR 15 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1746-1596 J9 DIAGN PATHOL JI Diagn. Pathol. PD JAN 27 PY 2016 VL 11 AR 13 DI 10.1186/s13000-016-0455-9 PG 5 WC Pathology SC Pathology GA DC1KW UT WOS:000368976200001 PM 26817999 ER PT J AU McCarthy, RC Lu, DY Alkhateeb, A Gardeck, AM Lee, CH Wessling-Resnick, M AF McCarthy, Ryan C. Lu, Dah-Yuu Alkhateeb, Ahmed Gardeck, Andrew M. Lee, Chih-Hao Wessling-Resnick, Marianne TI Characterization of a novel adult murine immortalized microglial cell line and its activation by amyloid-beta SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE BV-2 cells; Neurodegeneration; Microglia; Neuroinflammation; IMG cells; Amyloid-beta ID CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASE; MICE; NEUROINFLAMMATION; PHAGOCYTOSIS; INFLAMMATION; MACROPHAGES; DYSFUNCTION; EXPRESSION AB Background: Alzheimer's disease is associated with amyloid-beta (A beta)-induced microglia activation. This pro-inflammatory response promotes neuronal damage, and therapies are sought to limit microglial activation. Screening efforts to develop new pharmacological inhibitors require a robust in vitro cell system. Current models lack significant responses to A beta, and their use in examining age-related neurodegenerative diseases is questionable. For example, the commonly used BV-2 microglial line was derived from embryonic mononuclear cells and its activation by various stimuli is limited. To this end, we have established a new immortalized microglial (IMG) cell line from adult murine brain. The objective of this study was to characterize A beta-induced activation of IMG cells, and here, we demonstrate the ability of cannabinoids to significantly reduce this inflammatory response. Methods: Microglial cells derived from adult murine brain were immortalized via infection with the v-raf/v-myc retrovirus under conditions that selectively promote microglia growth. The presence or absence of markers CD11b and F4/80 (microglial), NeuN (neuronal), and GFAP (astrocytic) was assessed by immunofluorescence microscopy and western blotting. Using IMG and BV-2 cells, levels of pro-and anti-inflammatory transcripts in response to extracellular stimuli were determined by quantitative PCR (qPCR). Phagocytosis of fluorescent beads and fluorescein isothiocyanate (FITC)-labeled A beta oligomers was assessed using flow cytometry and fluorescence microscopy. FITC-A beta uptake was quantified using a fluorescence plate reader. The ability of cannabinoids to mitigate A beta-induced expression of inducible nitric oxide synthase (iNOS) was evaluated. Results: IMG cells express the microglial markers CD11b and F4/80 but not NeuN or GFAP. Relative to BV-2 cells, IMG cells increased iNOS (>200-fold) and Arg-1 (>100-fold) in response to pro-and anti-inflammatory stimuli. IMG cells phagocytose foreign particles and A beta oligomers, with the latter trafficked to phagolysosomes. A beta-induced activation of IMG cells was suppressed by delta-9-tetrahydrocannabinol and the CB2-selective agonist JWH-015 in a time-and concentration-dependent manner. Conclusions: IMG cells recapitulate key features of microglial cell activation. As an example of their potential pharmacological use, cannabinoids were shown to reduce activation of A beta-induced iNOS gene expression. IMG cells hold promising potential for drug screening, mechanistic studies, and functional investigations directed towards understanding how A beta interacts with microglia. C1 [McCarthy, Ryan C.; Lu, Dah-Yuu; Alkhateeb, Ahmed; Gardeck, Andrew M.; Lee, Chih-Hao; Wessling-Resnick, Marianne] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. [Lu, Dah-Yuu] China Med Univ, Grad Inst Neural & Cognit Sci, Taichung, Taiwan. [Alkhateeb, Ahmed] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Alkhateeb, Ahmed] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wessling-Resnick, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM wessling@hsph.harvard.edu FU National Institutes of Health grants from the National Institute of Environmental Health Sciences [R01 ES0146380]; National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK075046]; National Institute of Environmental Health Sciences [T32 ES016645] FX This study was supported by the National Institutes of Health grants from the National Institute of Environmental Health Sciences to MW-R (R01 ES0146380) and the National Institute of Diabetes and Digestive and Kidney Diseases to C-HL (R01 DK075046). RCM is supported by the National Institute of Environmental Health Sciences grant T32 ES016645. We thank Dr. Daniel J. Kosman for his generous donation of the C6 glioma cells and GFAP antibody. IMG cells have been deposited at KeraFAST. NR 42 TC 4 Z9 4 U1 2 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD JAN 27 PY 2016 VL 13 AR 21 DI 10.1186/s12974-016-0484-z PG 15 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA DC0DJ UT WOS:000368886900002 PM 26819091 ER PT J AU Gong, B Radulovic, M Figueiredo-Pereira, ME Cardozo, C AF Gong, Bing Radulovic, Miroslav Figueiredo-Pereira, Maria E. Cardozo, Christopher TI The Ubiquitin-Proteasome System: Potential Therapeutic Targets for Alzheimer's Disease and Spinal Cord Injury SO FRONTIERS IN MOLECULAR NEUROSCIENCE LA English DT Review DE ubiquitin-proteasome system; Alzheimer's disease; spinal cord injuries; beta-amyloid clearance; neuroregeneration ID AMYLOID PRECURSOR PROTEIN; TERMINAL HYDROLASE L1; AMYOTROPHIC-LATERAL-SCLEROSIS; PERIPHERAL NERVOUS-SYSTEM; FOCAL CEREBRAL-ISCHEMIA; BETA-SECRETASE BACE1; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASE; MITOCHONDRIAL DYSFUNCTION; TRANSIENT ISCHEMIA AB The ubiquitin-proteasome system (UPS) is a crucial protein degradation system in eukaryotes. Herein, we will review advances in the understanding of the role of several proteins of the UPS in Alzheimer's disease (AD) and functional recovery after spinal cord injury (SCI). The UPS consists of many factors that include E3 ubiquitin ligases, ubiquitin hydrolases, ubiquitin and ubiquitin-like molecules, and the proteasome itself. An extensive body of work links UPS dysfunction with AD pathogenesis and progression. More recently, the UPS has been shown to have vital roles in recovery of function after SCI. The ubiquitin hydrolase (Uch-L1) has been proposed to increase cellular levels of mono-ubiquitin and hence to increase rates of protein turnover by the UPS. A low Uch-L1 level has been linked with A beta accumulation in AD and reduced neuroregeneration after SCI. One likely mechanism for these beneficial effects of Uch-L1 is reduced turnover of the PKA regulatory subunit and consequently, reduced signaling via CREB. The neuron-specific F-box protein Fbx2 ubiquitinates beta-secretase thus targeting it for proteasomal degradation and reducing generation of A beta. Both Uch-L1 and Fbx2 improve synaptic plasticity and cognitive function in mouse AD models. The role of Fbx2 after SCI has not been examined, but abolishing B-secretase reduces neuronal recovery after SCI, associated with reduced myelination. UBB(+)1, which arises through a frame-shift mutation in the ubiquitin gene that adds 19 amino acids to the C-terminus of ubiquitin, inhibits proteasomal function and is associated with increased neurofibrillary tangles in patients with AD, Pick's disease and Down's syndrome. These advances in understanding of the roles of the UPS in AD and SCI raise new questions but, also, identify attractive and exciting targets for potential, future therapeutic interventions. C1 [Gong, Bing; Radulovic, Miroslav; Cardozo, Christopher] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Gong, Bing; Radulovic, Miroslav; Cardozo, Christopher] James J Peters Vet Affairs Med Ctr, Med, Bronx, NY USA. [Radulovic, Miroslav; Cardozo, Christopher] Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY USA. [Figueiredo-Pereira, Maria E.] CUNY Hunter Coll, Dept Biol Sci, New York, NY 10021 USA. [Figueiredo-Pereira, Maria E.] CUNY Grad Sch & Univ Ctr, New York, NY 10036 USA. RP Cardozo, C (reprint author), Mt Sinai Sch Med, Dept Med, New York, NY USA.; Cardozo, C (reprint author), James J Peters Vet Affairs Med Ctr, Med, Bronx, NY USA.; Cardozo, C (reprint author), Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY USA. EM christopher.cardozo@va.gov FU Alzheimer's Association [IIRG-12-242345]; Rehabilitation Research and Development Service Center for the Medical Consequences of Spinal Cord Injury [B9212C] FX The studies described here were supported in part by grant from Alzheimer's Association (IIRG-12-242345) to BC and by the Rehabilitation Research and Development Service Center for the Medical Consequences of Spinal Cord Injury (B9212C). We thank Dr. Anand and Mr. Jin for critical reading of the manuscript and preparation of the figures. NR 172 TC 5 Z9 5 U1 4 U2 16 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5099 J9 FRONT MOL NEUROSCI JI Front. Molec. Neurosci. PD JAN 26 PY 2016 VL 9 AR 4 DI 10.3389/fnmol.2015.00004 PG 16 WC Neurosciences SC Neurosciences & Neurology GA DE3UD UT WOS:000370554900002 PM 26858599 ER PT J AU Xu, NQ Fang, WF Mu, LB Tang, YN Gao, L Ren, SX Cao, DF Zhou, LX Zhang, AQ Liu, DR Zhou, CC Wong, KK Yu, L Zhang, L Chen, L AF Xu, Naiqing Fang, Wenfeng Mu, Libing Tang, Yanna Gao, Lei Ren, Shengxiang Cao, Dengfeng Zhou, Lixin Zhang, Aiqun Liu, Deruo Zhou, Caicun Wong, Kwok-Kin Yu, Lei Zhang, Li Chen, Liang TI Overexpression of wildtype EGFR is tumorigenic and denotes a therapeutic target in non-small cell lung cancer SO ONCOTARGET LA English DT Article DE EGFR; transgenic mouse model; tyrosine kinase inhibitor; lung cancer ID GROWTH-FACTOR-RECEPTOR; RANDOMIZED PHASE-3 TRIAL; KINASE DOMAIN MUTATIONS; GENE COPY NUMBER; 1ST-LINE TREATMENT; OPEN-LABEL; GEFITINIB SENSITIVITY; MOLECULAR PREDICTORS; EXPRESSION; ERLOTINIB AB Current guidelines for lung cancer treatment with EGFR tyrosine kinase inhibitors (TKI) include only patients with mutated EGFR, although some patients with wildtype EGFR (wt-EGFR) have exhibited positive responses to this therapy as well. Biomarkers predicting the benefit from EGFR-TKIs treatment remain to be determined for patients with wild-type EGFR. Here, we report that wt-EGFR overexpression transformed cells in vitro and induced tumorigenesis in vivo in transgenic mouse models. Wt-EGFR driven lung cancer was hypersensitive to TKI treatment in mouse model. Lung cancer patients with high-expression of wt-EGFR showed longer Overall Survival in comparison to low-expression patients after TKI treatment. Our data therefore suggest that treatment with EGFR inhibitors should be extended to include not only patients with mutated EGFR but also a subset of patients with overexpression of wt-EGFR. C1 [Xu, Naiqing; Chen, Liang] Peking Union Med Coll, Grad Sch, Beijing 100021, Peoples R China. [Xu, Naiqing; Gao, Lei; Chen, Liang] Natl Inst Biol Sci, Beijing, Peoples R China. [Xu, Naiqing; Chen, Liang] Chinese Acad Med Sci, Beijing 100730, Peoples R China. [Fang, Wenfeng; Tang, Yanna; Zhang, Li] Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Guangzhou 510275, Guangdong, Peoples R China. [Mu, Libing] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China. [Ren, Shengxiang; Zhou, Caicun] Shanghai Pulm Hosp, Shanghai, Peoples R China. [Cao, Dengfeng] Chinese Acad Med Sci, Canc Hosp & Inst, Beijing 100730, Peoples R China. [Zhou, Lixin] Peking Univ, Canc Hosp, Beijing 100871, Peoples R China. [Zhang, Aiqun] Gen Hosp Peoples Liberat Army, Beijing, Peoples R China. [Liu, Deruo] China Japan Friendship Hosp, Dept Thorac Surg, Beijing, Peoples R China. [Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yu, Lei] Capital Med Univ, Beijing Tongren Hosp, Beijing, Peoples R China. [Chen, Liang] Collaborat Innovat Ctr Canc Med, Natl Inst Biol Sci, Beijing, Peoples R China. RP Chen, L (reprint author), Peking Union Med Coll, Grad Sch, Beijing 100021, Peoples R China.; Chen, L (reprint author), Natl Inst Biol Sci, Beijing, Peoples R China.; Chen, L (reprint author), Chinese Acad Med Sci, Beijing 100730, Peoples R China.; Zhang, L (reprint author), Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Guangzhou 510275, Guangdong, Peoples R China.; Chen, L (reprint author), Collaborat Innovat Ctr Canc Med, Natl Inst Biol Sci, Beijing, Peoples R China. EM zhangli@sysucc.org.cn; chenliang@nibs.ac.cn FU Chinese Ministry of Science and Technology grant (973 grant) [2011CB812401]; National Natural Science Foundation of China [81472606]; Beijing Municipal Government FX This work was funded by Chinese Ministry of Science and Technology grant (973 grant) 2011CB812401, National Natural Science Foundation of China grant 81472606 and the Beijing Municipal Government to L.C.. NR 47 TC 1 Z9 1 U1 2 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 26 PY 2016 VL 7 IS 4 BP 3884 EP 3896 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DD5HA UT WOS:000369952400019 PM 26646697 ER PT J AU Park, C Ha, SY Kim, ST Kim, HC Heo, JS Park, YS Lauwers, G Lee, J Kim, KM AF Park, Charny Ha, Sang Yun Kim, Seung Tae Kim, Hee Cheol Heo, Jin Seok Park, Young Suk Lauwers, Gregory Lee, Jeeyun Kim, Kyoung-Mee TI Identification of the BRAF V600E mutation in gastroenteropancreatic neuroendocrine tumors SO ONCOTARGET LA English DT Article DE neuroendocrine tumors; BRAFV600E mutation; pazopanib ID CARCINOID-TUMORS; ENDOCRINE TUMORS; EPIDEMIOLOGY; RESISTANCE; DISCOVERY; MELANOMA; SURVIVAL; SAMPLES; GENES AB Genomic profiles of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are still insufficiently understood, and the genetic alterations associated with drug responses have not been studied. Here, we performed whole exome sequencing of 12 GEP-NETs from patients enrolled in a nonrandomized, open-labeled, single-center phase II study for pazopanib, and integrated our results with previously published results on pancreas (n = 12) and small intestine NETs (n = 50). The mean numbers of somatic mutations in each case varied widely from 20 to 4682. Among 12 GEP-NETs, eight showed mutations of more than one cancer-related gene, including TP53, CNBD1, RB1, APC, BCOR, BRAF, CTNNB1, EGFR, EP300, ERBB3, KDM6A, KRAS, MGA, MLL3, PTEN, RASA1, SMARCB1, SPEN, TBC1D12, and VHL. TP53 was recurrently mutated in three cases, whereas CNBD1 and RB1 mutations were identified in two cases. Three GEP-NET patients with TP53 mutations demonstrated a durable response and one small intestinal grade (G) 1 NET patient with BRAF V600E mutation showed progression after pazopanib treatment. We found BRAF V600E (G1 NET from rectum and two G3 NETs from colon) and BRAF G593S (G2 NET from pancreas) missense mutations (9.1%) in an independent cohort of 44 GEP-NETs from the rectum (n = 26), colon (n = 7), pancreas (n = 4), small intestine (n = 3), stomach (n = 3) and appendix (n = 1) by Sanger sequencing. All tumor specimens were obtained before chemotherapy. In conclusion, BRAF V600E mutation is likely to result in resistance to pazopanib but may be a potentianally actionable mutation in metastatic GEP-NETs patients. C1 [Park, Charny; Ha, Sang Yun; Kim, Kyoung-Mee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol & Translat Genom, Seoul, South Korea. [Kim, Seung Tae; Park, Young Suk; Lee, Jeeyun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med,Div Hematol Oncol, Seoul, South Korea. [Kim, Hee Cheol; Heo, Jin Seok] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Surg, Seoul, South Korea. [Lauwers, Gregory] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kim, KM (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol & Translat Genom, Seoul, South Korea.; Lee, J (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med,Div Hematol Oncol, Seoul, South Korea. EM jyunlee@skku.edu; kkmkys@skku.edu RI Lee, Jee Yun/C-9646-2011; kim, st/O-5928-2014 FU Korean Health Technology R & D Project, Ministry of Health & Welfare, Republic of Korea [HI14C3418] FX We would like to express our gratitude to Dr. Joshua Francis and Dr. Matthew Meyerson at the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA, and Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA, for genomic profiling of our tumor specimens, genomic analysis and helpful scientific advice. This work was partially supported by a grant from the Korean Health Technology R & D Project, Ministry of Health & Welfare, Republic of Korea (HI14C3418). NR 33 TC 2 Z9 3 U1 1 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 26 PY 2016 VL 7 IS 4 BP 4024 EP 4035 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DD5HA UT WOS:000369952400029 PM 26684240 ER PT J AU Choi, PW Yang, JZ Ng, SK Feltmate, C Muto, MG Hasselblatt, K Lafferty-Whyte, K JeBailey, L MacConaill, L Welch, WR Fong, WP Berkowitz, RS Ng, SW AF Choi, Pui-Wah Yang, Junzheng Ng, Shu-Kay Feltmate, Colleen Muto, Michael G. Hasselblatt, Kathleen Lafferty-Whyte, Kyle JeBailey, Lellean MacConaill, Laura Welch, William R. Fong, Wing-Ping Berkowitz, Ross S. Ng, Shu-Wing TI Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells SO ONCOTARGET LA English DT Article DE ovarian cancer; three-dimensional culture; inclusion cyst; tumor invasion; collective movement ID SURFACE EPITHELIUM; MIR-200 FAMILY; MOUSE-MODEL; LAYING HEN; EXPRESSION; INVASION; TRANSITION; CARCINOMA; MORPHOGENESIS; 3D AB Increased inclusion cyst formation in the ovary is associated with ovarian cancer development. We employed in vitro three-dimensional (3D) organotypic models formed by normal human ovarian surface epithelial (OSE) cells and ovarian cancer cells to study the morphologies of normal and cancerous ovarian cortical inclusion cysts and the molecular changes during their transitions into stromal microenvironment. When compared with normal cysts that expressed tenascin, the cancerous cysts expressed high levels of laminin V and demonstrated polarized structures in Matrigel; and the cancer cells migrated collectively when the cyst structures were positioned in a stromal-like collagen I matrix. The molecular markers identified in the in vitro 3D models were verified in clinical samples. Network analysis of gene expression of the 3D structures indicates concurrent downregulation of transforming growth factor beta pathway genes and high levels of E-cadherin and microRNA200 (miR200) expression in the cancerous cysts and the migrating cancer cells. Transient silencing of E-cadherin expression in ovarian cancer cells disrupted cyst structures and inhibited collective cell migration. Taken together, our studies employing 3D models have shown that E-cadherin is crucial for ovarian inclusion cyst formation and collective cancer cell migration. C1 [Choi, Pui-Wah; Fong, Wing-Ping] Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China. [Choi, Pui-Wah; Yang, Junzheng; Feltmate, Colleen; Muto, Michael G.; Hasselblatt, Kathleen; Berkowitz, Ross S.; Ng, Shu-Wing] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA. [Ng, Shu-Kay] Griffith Univ, Sch Med, Meadowbrook, Qld 4131, Australia. [Lafferty-Whyte, Kyle; JeBailey, Lellean] Thomson Reuters, GeneGo, New York, NY USA. [MacConaill, Laura] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Welch, William R.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RP Fong, WP (reprint author), Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China.; Ng, SW (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA. EM wpfong@cuhk.edu.hk; sng@partners.org FU Global Scholarship Program-CNOOC grant; Chinese University of Hong Kong; Robert and Deborah First Fund; Sperling Family Fund Foundation; Ruth N. White Gynecologic Oncology Research Fund; Women's Cancer Program; Gillette Center for Women's Cancer from Dana-Farber Cancer Institute; Ovarian Cancer Research Foundation; Adler Foundation, Inc.; Dana Farber Cancer Institute FX This work was partly supported by a Global Scholarship Program-CNOOC grant (to PWC), a Direct Grant for Research (2010/2011) of the Chinese University of Hong Kong (to WPF). We acknowledge the support of the Robert and Deborah First Fund, the Sperling Family Fund Foundation, Ruth N. White Gynecologic Oncology Research Fund, Women's Cancer Program and Gillette Center for Women's Cancer from Dana-Farber Cancer Institute, Ovarian Cancer Research Foundation, Adler Foundation, Inc., and Friends of Dana Farber Cancer Institute to The Laboratory of Gynecologic Oncology at Brigham and Women's Hospital. NR 50 TC 4 Z9 4 U1 1 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 26 PY 2016 VL 7 IS 4 BP 4110 EP 4121 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DD5HA UT WOS:000369952400035 PM 26684027 ER PT J AU Piccini, JP Hellkamp, AS Washam, JB Becker, RC Breithardt, G Berkowitz, SD Halperin, JL Hankey, GJ Hacke, W Mahaffey, KW Nessel, CC Singer, DE Fox, KAA Patel, MR AF Piccini, Jonathan P. Hellkamp, Anne S. Washam, Jeffrey B. Becker, Richard C. Breithardt, Guenter Berkowitz, Scott D. Halperin, Jonathan L. Hankey, Graeme J. Hacke, Werner Mahaffey, Kenneth W. Nessel, Christopher C. Singer, Daniel E. Fox, Keith A. A. Patel, Manesh R. TI Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation SO CIRCULATION LA English DT Article DE atrial fibrillation; factor Xa; pharmacokinetics; polypharmacy; rivaroxaban; warfarin ID RISK; CARE; AF AB Background Patients with atrial fibrillation (AF) often take multiple medications. Methods and Results We examined characteristics and compared adjusted outcomes between rivaroxaban and warfarin according to number of concomitant baseline medications and the presence of combined cytochrome P450 3A4 and P-glycoprotein inhibitors in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study. At baseline, 5101 patients (36%) were on 0 to 4 medications, 7298 (51%) were on 5 to 9, and 1865 (13%) were on 10. Although polypharmacy was not associated with higher risk of stroke or non-central nervous system embolism (adjusted hazard ratio, 1.02 for 10 versus 0-4 medications; 95% confidence interval, 0.76-1.38), it was associated with higher risks of the combined end point of stroke, non-central nervous system embolism, vascular death, or myocardial infarction (adjusted hazard ratio, 1.41 for 10 versus 0-4 medications; 95% confidence interval, 1.18-1.68) and nonmajor clinically relevant or major bleeding (adjusted hazard ratio, 1.47 for 10 versus 0-4 medications; 95% confidence interval, 1.31-1.65). There was no significant difference in primary efficacy (adjusted interaction P=0.99) or safety outcomes (adjusted interaction P=0.87) between treatment groups by number of medications. Patients treated with 0 to 4 medications had lower rates of major bleeding with rivaroxaban (adjusted hazard ratio, 0.71; 95% confidence interval, 0.52-0.95; interaction P=0.0074). There was no evidence of differential outcomes in those treated with 1 combined cytochrome P450 3A4 and P-glycoprotein inhibitors. Conclusions In a population of patients with atrial fibrillation, two thirds were on 5 medications. Increasing medication use was associated with higher risk of bleeding but not stroke. Rivaroxaban was tolerated across complex patients on multiple medications. C1 [Piccini, Jonathan P.; Hellkamp, Anne S.; Patel, Manesh R.] Duke Clin Res Inst, Durham, NC USA. [Piccini, Jonathan P.; Washam, Jeffrey B.; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Heart Ctr, Room 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA. [Becker, Richard C.] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. [Breithardt, Guenter] Hosp Univ Munster, Munster, Germany. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Zena & Michael A Wiener Cardiovascular Inst, New York, NY 10029 USA. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Mahaffey, Kenneth W.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. [Nessel, Christopher C.] Janssen Pharmaceut Res & Dev, Raritan, NJ USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm, Edinburgh, Midlothian, Scotland. RP Piccini, JP (reprint author), Duke Clin Res Inst, Durham, NC USA.; Piccini, JP (reprint author), Duke Univ, Med Ctr, Duke Heart Ctr, Room 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA.; Piccini, JP (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Room 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA. EM jonathan.piccini@duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson & Johnson Pharmaceutical Research & Development (Raritan, NJ); Bayer HealthCare AG (Leverkusen, Germany) FX ROCKET AF was supported by Johnson & Johnson Pharmaceutical Research & Development (Raritan, NJ) and Bayer HealthCare AG (Leverkusen, Germany). NR 16 TC 13 Z9 13 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 26 PY 2016 VL 133 IS 4 BP 352 EP 360 DI 10.1161/CIRCULATIONAHA.115.018544 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DC5KE UT WOS:000369259100003 PM 26673560 ER PT J AU Ma, JT McKeown, NM Hwang, SJ Hoffmann, U Jacques, PF Fox, CS AF Ma, Jiantao McKeown, Nicola M. Hwang, Shih-Jen Hoffmann, Udo Jacques, Paul F. Fox, Caroline S. TI Sugar-Sweetened Beverage Consumption Is Associated With Change of Visceral Adipose Tissue Over 6 Years of Follow-Up SO CIRCULATION LA English DT Article DE obesity; subcutaneous adipose tissue; visceral adipose tissue ID FOOD-FREQUENCY QUESTIONNAIRE; LIPOPROTEIN-LIPASE; METABOLIC SYNDROME; UNITED-STATES; FRUCTOSE; DISEASE; FAT; REPRODUCIBILITY; VALIDITY; INSULIN AB Background Sugar-sweetened beverage (SSB) intake has been linked to abnormal abdominal adipose tissue. We examined the prospective association of habitual SSB intake and change in visceral adipose tissue (VAT) and subcutaneous adipose tissue. Methods and Results The quantity (volume, cm(3)) and quality (attenuation, Hounsfield Unit) of abdominal adipose tissue were measured using computed tomography in 1003 participants (mean age 45.3 years, 45.0% women) at examination 1 and 2 in the Framingham's Third Generation cohort. The 2 exams were approximate to 6 years apart. At baseline, SSB and diet soda intake were assessed using a valid food frequency questionnaire. Participants were categorized into 4 groups: none to <1 serving/mo (nonconsumers), 1 serving/mo to <1 serving/week, 1 serving/week to 1 serving/d, and 1 serving/d (daily consumers) of either SSB or diet soda. After adjustment for multiple confounders including change in body weight, higher SSB intake was associated with greater change in VAT volume (P trend<0.001). VAT volume increased by 658 cm(3) (95% confidence interval [CI], 602 to 713), 649 cm(3) (95% CI, 582 to 716), 707 cm(3) (95% CI, 657 to 757), and 852 cm(3) (95% CI, 760 to 943) from nonconsumers to daily consumers. Higher SSB intake was also associated with greater decline of VAT attenuation (P trend=0.007); however, the association became nonsignificant after additional adjustment for VAT volume change. In contrast, diet soda consumption was not associated with change in abdominal adipose tissue. Conclusions Regular SSB intake was associated with adverse change in both VAT quality and quantity, whereas we observed no such association for diet soda. C1 [Ma, Jiantao; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study & Populat Sci Branch, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. [McKeown, Nicola M.; Jacques, Paul F.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA. [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study & Populat Sci Branch, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxa@nhlbi.nih.gov FU Framingham Heart Study (FHS) of National Heart, Lung, and Blood Institute (NHLBI) of National Institute of Health; Boston University School of Medicine; NHLBI FHS [N01-HC-25195] FX This work was conducted in part using resources and data from the Framingham Heart Study (FHS) of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institute of Health and Boston University School of Medicine. This work was supported by the NHLBI FHS (N01-HC-25195). NR 35 TC 2 Z9 2 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 26 PY 2016 VL 133 IS 4 BP 370 EP 377 DI 10.1161/CIRCULATIONAHA.115.018704 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DC5KE UT WOS:000369259100005 PM 26755505 ER PT J AU Ghaoui, R Palmio, J Brewer, J Lek, M Needham, M Evila, A Hackman, P Jonson, PH Penttila, S Vihola, A Huovinen, S Lindfors, M Davis, RL Waddell, L Kaur, S Yiannikas, C North, K Clarke, N MacArthur, DG Sue, CM Udd, B AF Ghaoui, Roula Palmio, Johanna Brewer, Janice Lek, Monkol Needham, Merrilee Evila, Anni Hackman, Peter Jonson, Per-Harald Penttila, Sini Vihola, Anna Huovinen, Sanna Lindfors, Mikaela Davis, Ryan L. Waddell, Leigh Kaur, Simran Yiannikas, Con North, Kathryn Clarke, Nigel MacArthur, Daniel G. Sue, Carolyn M. Udd, Bjarne TI Mutations in HSPB8 causing a new phenotype of distal myopathy and motor neuropathy SO NEUROLOGY LA English DT Article ID MARIE-TOOTH DISEASE; GIRDLE MUSCULAR-DYSTROPHY; HEAT-SHOCK-PROTEIN; PEDIGREE; DNAJB6; 2L AB Objective:To report novel disease and pathology due to HSPB8 mutations in 2 families with autosomal dominant distal neuromuscular disease showing both myofibrillar and rimmed vacuolar myopathy together with neurogenic changes.Methods:We performed whole-exome sequencing (WES) in tandem with linkage analysis and candidate gene approach as well as targeted next-generation sequencing (tNGS) to identify causative mutations in 2 families with dominant rimmed vacuolar myopathy and a motor neuropathy. Pathogenic variants and familial segregation were confirmed using Sanger sequencing.Results:WES and tNGS identified a heterozygous change in HSPB8 in both families: c.421A > G p.K141E in family 1 and c.151insC p.P173SfsX43 in family 2. Affected patients had a distal myopathy that showed myofibrillar aggregates and rimmed vacuoles combined with a clear neurogenic component both on biopsy and neurophysiologic studies. MRI of lower limb muscles demonstrated diffuse tissue changes early in the disease stage progressing later to fatty replacement typical of a myopathy.Conclusion:We expand the understanding of disease mechanisms, tissue involvement, and phenotypic outcome of HSPB8 mutations. HSPB8 is part of the chaperone-assisted selective autophagy (CASA) complex previously only associated with Charcot-Marie-Tooth type 2L (OMIM 60673) and distal hereditary motor neuronopathy type IIa. However, we now demonstrate that patients can develop a myopathy with histologic features of myofibrillar myopathy with aggregates and rimmed vacuoles, similar to the pathology in myopathies due to gene defects in other compounds of the CASA complex such as BAG3 and DNAJB6 after developing the early neurogenic effects. C1 [Ghaoui, Roula; Waddell, Leigh; Kaur, Simran; Clarke, Nigel] Childrens Hosp, Inst Neurosci & Muscle Res, Kids Res Inst, Westmead, NSW, Australia. [Ghaoui, Roula; Davis, Ryan L.; Waddell, Leigh; Kaur, Simran; Yiannikas, Con; Clarke, Nigel; Sue, Carolyn M.] Univ Sydney, Sydney, NSW 2006, Australia. [Palmio, Johanna; Penttila, Sini; Lindfors, Mikaela; Udd, Bjarne] Tampere Univ Hosp, Neuromuscular Res Ctr, Dept Neurol, Tampere, Finland. [Huovinen, Sanna] Tampere Univ Hosp, Dept Pathol, Fimlab Labs, Tampere, Finland. [Huovinen, Sanna] Univ Tampere, FIN-33101 Tampere, Finland. [Brewer, Janice] Royal N Shore Hosp, Dept Pathol, Sydney, NSW, Australia. [Lek, Monkol; MacArthur, Daniel G.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Needham, Merrilee] Univ Western Australia, Western Australian Neurosci Res Inst, Perth, WA 6009, Australia. [Evila, Anni; Hackman, Peter; Jonson, Per-Harald; Vihola, Anna; Udd, Bjarne] Univ Helsinki, Folkhalsan Inst Genet, FIN-00014 Helsinki, Finland. [Evila, Anni; Hackman, Peter; Jonson, Per-Harald; Vihola, Anna; Udd, Bjarne] Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland. [Davis, Ryan L.; Yiannikas, Con; Sue, Carolyn M.] Royal N Shore Hosp, Dept Neurogenet, Kolling Inst, St Leonards, NSW, Australia. [North, Kathryn] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Udd, Bjarne] Vaasa Cent Hosp, Dept Neurol, Vaasa, Finland. RP Sue, CM (reprint author), Univ Sydney, Sydney, NSW 2006, Australia.; Udd, B (reprint author), Tampere Univ Hosp, Neuromuscular Res Ctr, Dept Neurol, Tampere, Finland.; Udd, B (reprint author), Univ Helsinki, Folkhalsan Inst Genet, FIN-00014 Helsinki, Finland.; Udd, B (reprint author), Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland.; Sue, CM (reprint author), Royal N Shore Hosp, Dept Neurogenet, Kolling Inst, St Leonards, NSW, Australia.; Udd, B (reprint author), Vaasa Cent Hosp, Dept Neurol, Vaasa, Finland. EM Carolyn.sue@sydney.edu.au; Bjarne.udd@netikka.fi FU Australian National Health and Medical Research Council (NHMRC) [APP1074954, APP1031893, APP1022707, APP1035828, APP1008433, APP1037797]; Muscular Dystrophy New South Wales; National Human Genome Research Institute of the NIH [U54 HG003067]; Juselius Foundation; Finnish Academy; Folkhalsan Foundation FX This project was supported by Australian National Health and Medical Research Council (NHMRC) grants: APP1074954 (R. Ghaoui), APP1031893 and APP1022707 (K.N. North and N.F. Clarke), APP1035828 (N.F. Clarke), APP1008433 (C.M. Sue), APP1037797 (R.L. Davis), and Muscular Dystrophy New South Wales (R. Ghaoui). Exome sequencing was supported by grants from the National Human Genome Research Institute of the NIH (Medical Sequencing Program grant U54 HG003067 to the Broad Institute principal investigator, E. Lander). Also supported by Juselius Foundation, Finnish Academy, and the Folkhalsan Foundation (B. Udd). NR 18 TC 8 Z9 8 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 26 PY 2016 VL 86 IS 4 BP 391 EP 398 DI 10.1212/WNL.0000000000002324 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DC5LV UT WOS:000369263400007 PM 26718575 ER PT J AU Choi, YE Meghani, K Brault, ME Leclerc, L He, YZJ Day, TA Elias, KM Drapkin, R Weinstock, DM Dao, F Shih, KK Matulonis, U Levine, DA Konstantinopoulos, PA Chowdhury, D AF Choi, Young Eun Meghani, Khyati Brault, Marie-Eve Leclerc, Lucas He, Yizhou J. Day, Tovah A. Elias, Kevin M. Drapkin, Ronny Weinstock, David M. Dao, Fanny Shih, Karin K. Matulonis, Ursula Levine, Douglas A. Konstantinopoulos, Panagiotis A. Chowdhury, Dipanjan TI Platinum and PARP Inhibitor Resistance Due to Overexpression of MicroRNA-622 in BRCA1-Mutant Ovarian Cancer SO CELL REPORTS LA English DT Article ID DNA-DAMAGE; CELL-CYCLE; HOMOLOGOUS RECOMBINATION; REPAIR; DEFICIENCY; RESECTION; BREAKS; 53BP1; KU AB High-grade serous ovarian carcinomas (HGSOCs) with BRCA1/2 mutations exhibit improved outcome and sensitivity to double-strand DNA break (DSB)inducing agents (i.e., platinum and poly(ADP-ribose) polymerase inhibitors [PARPis]) due to an underlying defect in homologous recombination (HR). However, resistance to platinum and PARPis represents a significant barrier to the long-term survival of these patients. Although BRCA1/2-reversion mutations are a clinically validated resistance mechanism, they account for less than half of platinum-resistant BRCA1/2-mutated HGSOCs. We uncover a resistance mechanism by which a microRNA, miR-622, induces resistance to PARPis and platinum in BRCA1 mutant HGSOCs by targeting the Ku complex and restoring HR-mediated DSB repair. Physiologically, miR-622 inversely correlates with Ku expression during the cell cycle, suppressing non-homologous end-joining and facilitating HR-mediated DSB repair in S phase. Importantly, high expression of miR-622 in BRCA1-deficient HGSOCs is associated with worse outcome after platinum chemotherapy, indicating microRNA-mediated resistance through HR rescue. C1 [Choi, Young Eun; Meghani, Khyati; Brault, Marie-Eve; Leclerc, Lucas; He, Yizhou J.; Chowdhury, Dipanjan] Harvard Univ, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair, Dept Radiat Oncol,Sch Med, Boston, MA 02215 USA. [Day, Tovah A.; Weinstock, David M.; Matulonis, Ursula; Konstantinopoulos, Panagiotis A.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Elias, Kevin M.] Brigham & Womens Hosp, Dept Obstet & Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02215 USA. [Drapkin, Ronny] Univ Penn, Perelman Sch Med, Dept Obstet & Gynecol, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. [Dao, Fanny; Shih, Karin K.; Levine, Douglas A.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA. RP Chowdhury, D (reprint author), Harvard Univ, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair, Dept Radiat Oncol,Sch Med, Boston, MA 02215 USA.; Konstantinopoulos, PA (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. EM panagiotis_konstantinopoulos@dfci.harvard.edu; dipanjan_chowdhury@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016; OI Drapkin, Ronny/0000-0002-6912-6977; He, Yizhou/0000-0002-1396-7275 FU Basic Scholar Grant (American Cancer Society); Leukemia and Lymphoma Society Scholar Grant; Claudia Adams Barr Program for Innovative Cancer Research; Breast SPORE Pilot Award; Robert and Deborah First Fund; Mary Kay Foundation; Susan Smith Center for Women's Cancers; Department of Defense Ovarian Cancer Academy Award [W81XWH-10-1-0585]; [R01 AI101897-01]; [R01CA142698-07] FX D.C. is supported by grants R01 AI101897-01 (NIAID) and R01CA142698-07 (NCI), a Basic Scholar Grant (American Cancer Society), a Leukemia and Lymphoma Society Scholar Grant, the Claudia Adams Barr Program for Innovative Cancer Research, a Breast SPORE Pilot Award, the Robert and Deborah First Fund, and the Mary Kay Foundation. P.A.K. is supported by the Susan Smith Center for Women's Cancers and a Department of Defense Ovarian Cancer Academy Award (W81XWH-10-1-0585). The Brca1-/- MEFs were a gift from Andre Nussenzweig, and NHEJ reporter construct was a gift from Jeremy Stark. NR 29 TC 3 Z9 3 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD JAN 26 PY 2016 VL 14 IS 3 BP 429 EP 439 DI 10.1016/j.celrep.2015.12.046 PG 11 WC Cell Biology SC Cell Biology GA DB7NF UT WOS:000368701600004 PM 26774475 ER PT J AU Heyn, H Vidal, E Ferreira, HJ Vizoso, M Sayols, S Gomez, A Moran, S Boque-Sastre, R Guil, S Martinez-Cardus, A Lin, CY Royo, R Sanchez-Mut, JV Martinez, R Gut, M Torrents, D Orozco, M Gut, I Young, RA Esteller, M AF Heyn, Holger Vidal, Enrique Ferreira, Humberto J. Vizoso, Miguel Sayols, Sergi Gomez, Antonio Moran, Sebastian Boque-Sastre, Raquel Guil, Sonia Martinez-Cardus, Anna Lin, Charles Y. Royo, Romina Sanchez-Mut, Jose V. Martinez, Ramon Gut, Marta Torrents, David Orozco, Modesto Gut, Ivo Young, Richard A. Esteller, Manel TI Epigenomic analysis detects aberrant super-enhancer DNA methylation in human cancer SO GENOME BIOLOGY LA English DT Article DE Super-enhancer; DNA methylation; Epigenomics; Cancer ID REGULATORY ELEMENTS; CONTROL REGION; CELL IDENTITY; HUMAN GENOME; GENE; TRANSCRIPTION; EXPRESSION; FEATURES; INHIBITION; CLONING AB Background: One of the hallmarks of cancer is the disruption of gene expression patterns. Many molecular lesions contribute to this phenotype, and the importance of aberrant DNA methylation profiles is increasingly recognized. Much of the research effort in this area has examined proximal promoter regions and epigenetic alterations at other loci are not well characterized. Results: Using whole genome bisulfite sequencing to examine uncharted regions of the epigenome, we identify a type of far reaching DNA methylation alteration in cancer cells of the distal regulatory sequences described as super-enhancers. Human tumors undergo a shift in super-enhancer DNA methylation profiles that is associated with the transcriptional silencing or the overactivation of the corresponding target genes. Intriguingly, we observe locally active fractions of super-enhancers detectable through hypomethylated regions that suggest spatial variability within the large enhancer clusters. Functionally, the DNA methylomes obtained suggest that transcription factors contribute to this local activity of super-enhancers and that trans-acting factors modulate DNA methylation profiles with impact on transforming processes during carcinogenesis. Conclusions: We develop an extensive catalogue of human DNA methylomes at base resolution to better understand the regulatory functions of DNA methylation beyond those of proximal promoter gene regions. CpG methylation status in normal cells points to locally active regulatory sites at super-enhancers, which are targeted by specific aberrant DNA methylation events in cancer, with putative effects on the expression of downstream genes. C1 [Heyn, Holger; Vidal, Enrique; Ferreira, Humberto J.; Vizoso, Miguel; Sayols, Sergi; Gomez, Antonio; Moran, Sebastian; Boque-Sastre, Raquel; Guil, Sonia; Martinez-Cardus, Anna; Sanchez-Mut, Jose V.; Esteller, Manel] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain. [Lin, Charles Y.; Young, Richard A.] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. [Lin, Charles Y.] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA. [Lin, Charles Y.] Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Royo, Romina; Torrents, David; Orozco, Modesto] Joint Biomed Res Inst Barcelona Supercomp Ctr IRB, Program Computat Biol, Baldiri Reixac 10-12, Barcelona 08028, Catalonia, Spain. [Martinez, Ramon] Univ Gottingen, Dept Neurosurg, Robert Koch Str 40, D-37075 Gottingen, Germany. [Gut, Marta] Ctr Nacl Anal Genom, Barcelona, Catalonia, Spain. [Torrents, David; Esteller, Manel] ICREA, Barcelona 08010, Catalonia, Spain. [Orozco, Modesto] Inst Res Biomed IRB Barcelona, Baldiri Reixac 10-12, Barcelona 08028, Catalonia, Spain. [Orozco, Modesto] Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Catalonia, Spain. [Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Esteller, Manel] Univ Barcelona, Dept Physiol Sci 2, Sch Med, E-08036 Barcelona, Catalonia, Spain. RP Heyn, H; Esteller, M (reprint author), Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain. EM hheyn@idibell.cat; mesteller@idibell.cat RI Moran, Sebastian /G-5293-2013; Guil, Sonia/M-8036-2015; Torrents, David/G-5785-2015; OI Heyn, Holger/0000-0002-3276-1889; Moran, Sebastian /0000-0003-4192-8983; Guil, Sonia/0000-0002-2257-3331; Torrents, David/0000-0002-6086-9037; Ferreira, Humberto/0000-0003-0834-2956; Esteller, Manel/0000-0003-4490-6093; Sayols, Sergi/0000-0002-3877-4170 FU European Research Council (ERC), grant EPINORC [268626]; MICINN Projects [SAF2011-22803, BFU2011-28549]; Ministerio de Economia y Competitividad (MINECO); Cellex Foundation; AGAUR Catalan Government Project [2009SGR1315]; Institute of Health Carlos III (ISCIII), under the Spanish Cancer Research Network (RTICC) [RD12/0036/0039]; Sandra Ibarra Foundation, under IV ghd Grants for breast cancer research; Olga Torres Foundation; European Community [HEALTH-F5-2011-282510 - BLUEPRINT]; Health and Science Departments of the Generalitat de Catalunya; Spanish Institute of Health Carlos III (ISCIII) [CP14/00229]; European Development Regional Fund, 'A way to achieve Europe' ERDF [SAF2014-55000-R]; Institute of Health Carlos III (ISCIII), under the Integrated Project of Excellence [PIE13/00022]; Institute of Health Carlos III (ISCIII) [PI11/00321] FX The research leading to these results received funding from: the European Research Council (ERC), grant EPINORC, under agreement number 268626; MICINN Projects - SAF2011-22803 and BFU2011-28549; Ministerio de Economia y Competitividad (MINECO), co-financed by the European Development Regional Fund, 'A way to achieve Europe' ERDF, under grant number SAF2014-55000-R; the Cellex Foundation; AGAUR Catalan Government Project #2009SGR1315; the Institute of Health Carlos III (ISCIII), under the Spanish Cancer Research Network (RTICC) number RD12/0036/0039, the Integrated Project of Excellence number PIE13/00022 (ONCOPROFILE) and the research grant PI11/00321; the Sandra Ibarra Foundation, under IV ghd Grants for breast cancer research; the Olga Torres Foundation; the European Community's Seventh Framework Programme (FP7/2007-2013), grant HEALTH-F5-2011-282510 - BLUEPRINT, and the Health and Science Departments of the Generalitat de Catalunya. H.H. is a Miguel Servet (CP14/00229) researcher funded by the Spanish Institute of Health Carlos III (ISCIII). D.T. and M.E. are ICREA Research Professors. NR 56 TC 15 Z9 15 U1 21 U2 57 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PD JAN 26 PY 2016 VL 17 AR 11 DI 10.1186/s13059-016-0879-2 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DC0JU UT WOS:000368903900002 PM 26813288 ER PT J AU Barnhart, C McClymont, K Smith, AK Au-Yeung, A Lee, SJ AF Barnhart, Caroline McClymont, Keelan Smith, Alex K. Au-Yeung, Alvin Lee, Sei J. TI "Everyone else gets ice cream here more often than I do-It burns me up" - Perspectives on Diabetes Care from Nursing Home Residents and their Doctors SO BMC GERIATRICS LA English DT Article DE Diabetes mellitus; Quality of Life; Geriatrics; Fingerstick ID OLDER PATIENTS; MELLITUS; PREVALENCE; MANAGEMENT; PEOPLE; ADULTS; GOALS AB Background: To explore the perspectives of nursing home (NH) residents with diabetes and their doctors regarding the burdens of living with diabetes and diabetes treatments. Methods: Qualitative study of nursing home residents aged 65 and older with diabetes (n = 14) and nursing home physicians (n = 9) at a Department of Veterans Affairs nursing home (known as the Community Living Center). A semi-structured interview was used to elicit nursing home residents' and physicians' perspectives on the burden of diabetes and diabetes treatments. Transcripts were analyzed using constant comparative methods. Results: The mean age of the nursing home residents was 74; Most (93 %) were male and 50 % self-identified themselves as white. The mean age of nursing home physicians was 39 and 55 % were geriatricians. Dietary restrictions, loss of independence and fingersticks/insulin were noted to be the most burdensome aspects of diabetes. Nursing home residents with a more positive outlook were generally more engaged in their care, while nursing home residents with a more pessimistic outlook were less engaged, allowing their physicians to assume complete control of their care. While physicians noted the potential negative impact of dietary restrictions, nursing home residents' comments suggest that physicians underestimate the burden of dietary restrictions. Conclusions: Veterans Affairs nursing home residents were substantially burdened by their diabetes treatments, especially dietary restrictions and fingerstick monitoring. Since there is little evidence that dietary restrictions improve outcomes, fewer dietary restrictions may be appropriate and lead to lower treatment burdens for nursing home residents with diabetes. C1 [Barnhart, Caroline; McClymont, Keelan; Smith, Alex K.; Au-Yeung, Alvin; Lee, Sei J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Barnhart, Caroline; McClymont, Keelan; Smith, Alex K.; Au-Yeung, Alvin; Lee, Sei J.] Univ Calif San Francisco, San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,Bldg 1,Room 220 F, San Francisco, CA 94121 USA. RP Lee, SJ (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.; Lee, SJ (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,Bldg 1,Room 220 F, San Francisco, CA 94121 USA. EM sei.lee@ucsf.edu FU National Institute on Aging at the National Institutes of Health; American Federation for Aging Research [K23AG040779]; UCSF Claude D. Pepper Older Americans Independence Center [P30AG044281] FX This work was supported by the National Institute on Aging at the National Institutes of Health and the American Federation for Aging Research through the Beeson Career Development [K23AG040779]. This work was also supported by the UCSF Claude D. Pepper Older Americans Independence Center [P30AG044281]. NR 24 TC 0 Z9 0 U1 3 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2318 J9 BMC GERIATR JI BMC Geriatr. PD JAN 26 PY 2016 VL 16 AR 28 DI 10.1186/s12877-016-0199-0 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DB5SG UT WOS:000368573300001 PM 26813788 ER PT J AU Siu, AL Bibbins-Domingo, K Grossman, DC 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 AF Siu, Albert L. Bibbins-Domingo, Kirsten Grossman, David C. Baumann, Linda Ciofu Davidson, Karina W. Ebell, Mark Garcia, Francisco A. R. Gillman, Matthew Herzstein, Jessica Kemper, Alex R. Krist, Alex H. Kurth, Ann E. Owens, Douglas K. Phillips, William R. Phipps, Maureen G. Pignone, Michael P. CA USPSTF TI Screening for Depression in Adults US Preventive Services Task Force Recommendation Statement SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; PRIMARY-CARE; POSTPARTUM DEPRESSION; PERINATAL DEPRESSION; POSTNATAL DEPRESSION; QUALITY IMPROVEMENT; WOMEN; PHARMACOTHERAPY; SYMPTOMATOLOGY AB DESCRIPTION Update of the 2009 US Preventive Services Task Force (USPSTF) recommendation on screening for depression in adults. METHODS The USPSTF reviewed the evidence on the benefits and harms of screening for depression in adult populations, including older adults and pregnant and postpartum women; the accuracy of depression screening instruments; and the benefits and harms of depression treatment in these populations. POPULATION This recommendation applies to adults 18 years and older. RECOMMENDATION The USPSTF recommends screening for depression in the general adult population, including pregnant and postpartum women. Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up. (B recommendation) 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 C.] Grp Hlth Res Inst, Seattle, WA USA. [Baumann, Linda Ciofu] Univ Wisconsin, Madison, WI 53706 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, Alex H.] Virginia Commonwealth Univ, Richmond, VA 23284 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), Mt Sinai Sch Med, New York, NY USA.; Siu, AL (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY USA. EM albert.siu@mssm.edu OI Phillips, William/0000-0003-2802-4349 FU USPSTF FX The USPSTF is an independent, voluntary body. The US Congress mandates that the Agency for Healthcare Research and Quality (AHRQ) support the operations of the USPSTF. NR 34 TC 80 Z9 81 U1 5 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 26 PY 2016 VL 315 IS 4 BP 380 EP 387 DI 10.1001/jama.2015.18392 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DB5YI UT WOS:000368589500016 PM 26813211 ER PT J AU Ashburner, JM Go, AS Chang, YC Fang, MC Fredman, L Applebaum, KM Singer, DE AF Ashburner, Jeffrey M. Go, Alan S. Chang, Yuchiao Fang, Margaret C. Fredman, Lisa Applebaum, Katie M. Singer, Daniel E. TI Effect of Diabetes and Glycemic Control on Ischemic Stroke Risk in AF Patients ATRIA Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atrial fibrillation; diabetes mellitus; stroke ID STRATIFICATION SCHEMES; ATHEROSCLEROSIS RISK; FIBRILLATION ATRIA; PREDICTING STROKE; ANTICOAGULATION; PREVENTION; TRIALS; ASSOCIATION; COMMUNITIES; POPULATION AB BACKGROUND Diagnosed diabetes mellitus (DM) is a consistently documented risk factor for ischemic stroke in patients with atrial fibrillation (AF). OBJECTIVES The purpose of this study was to assess the association between duration of diabetes and elevated hemoglobin A1c (HbA1c) with risk of stroke among diabetic patients with AF. METHODS We assessed this association in the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) California community-based cohort of AF patients (study years 1996 to 2003) where all events were clinician adjudicated. We used Cox proportional hazards regression to estimate the rate of ischemic stroke in diabetic patients according to time-varying measures of estimated duration of diabetes (>= 3 years compared with <3 years) and HbA1c values (>= 9.0% and 7.0% to 8.9% compared with <7.0%), focusing on periods where patients were not anticoagulated. RESULTS There were 2,101 diabetic patients included in the duration analysis: 40% with duration <3 years and 60% with duration >= 3 years at baseline. Among 1,933 diabetic patients included in the HbA1c analysis, 46% had HbA1c <7.0%, 36% between 7.0% and 8.9%, and 19% >= 9.0% at baseline. Duration of diabetes >= 3 years was associated with an increased rate of ischemic stroke compared with duration <3 years (adjusted hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.10 to 2.76). The increased stroke rate was observed in older (age >= 75 years) and younger (age <75 years) individuals. Neither poor glycemic control (HbA1c >= 9.0%, adjusted HR: 1.04, 95% CI: 0.57 to 1.92) nor moderately increased HbA1c (7.0% to 8.9%, adjusted HR: 1.21, 95% CI: 0.77 to 1.91) were significantly associated with an increased rate of ischemic stroke compared with patients who had HbA1c <7.0%. CONCLUSIONS Duration of diabetes is a more important predictor of ischemic stroke than glycemic control in patients who have diabetes and AF. (C) 2016 by the American College of Cardiology Foundation. C1 [Ashburner, Jeffrey M.; Chang, Yuchiao; Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. [Ashburner, Jeffrey M.; Chang, Yuchiao; Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Ashburner, Jeffrey M.; Fredman, Lisa] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol Biostat & Med, San Francisco, CA 94143 USA. [Go, Alan S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Fang, Margaret C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Applebaum, Katie M.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Environm & Occupat Hlth, Washington, DC USA. [Applebaum, Katie M.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RP Ashburner, JM (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jashburner@mgh.harvard.edu FU National Institute on Aging [R01 AG15478, K23 AG028978]; National Heart, Lung, and Blood Institute [U19 HL91179, RC2HL101589]; Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital; iRhythm; CSL Behring FX This study was supported by the National Institute on Aging (R01 AG15478 and K23 AG028978), the National Heart, Lung, and Blood Institute (U19 HL91179 and RC2HL101589), and the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital. The funding sources had no role in study design, data collection, data analysis, data interpretation, or preparation of the manuscript. Dr. Go has received a research grant from iRhythm and CSL Behring. Dr. Singer serves as a consultant/advisory board member for Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, CVS Heath, Johnson & Johnson, Medtronic, Pfizer, and St. Jude Medical on matters related to preventing stroke in atrial fibrillation; and has research contracts with Medtronic, Inc., related to atrial fibrillation and risk of stroke, with Johnson & Johnson related to stroke prevention in atrial fibrillation, and with Bristol-Myers Squibb related to atrial fibrillation and risk of stroke. All other authors have reported that they have no relationships relevant to the contents of this paper. NR 29 TC 9 Z9 9 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 26 PY 2016 VL 67 IS 3 BP 239 EP 247 DI 10.1016/j.jacc.2015.10.080 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB5NM UT WOS:000368560900001 PM 26796386 ER PT J AU Dal-Bianco, JP Aikawa, E Bischoff, J Guerrero, JL Hjortnaes, J Beaudoin, J Szymanski, C Bartko, PE Seybolt, MM Handschumacher, MD Sullivan, S Garcia, ML Mauskapf, A Titus, JS Wylie-Sears, J Irvin, WS Chaput, M Messas, E Hagege, AA Carpentier, A Levine, RA AF Dal-Bianco, Jacob P. Aikawa, Elena Bischoff, Joyce Guerrero, J. Luis Hjortnaes, Jesper Beaudoin, Jonathan Szymanski, Catherine Bartko, Philipp E. Seybolt, Margo M. Handschumacher, Mark D. Sullivan, Suzanne Garcia, Michael L. Mauskapf, Adam Titus, James S. Wylie-Sears, Jill Irvin, Whitney S. Chaput, Miguel Messas, Emmanuel Hagege, Albert A. Carpentier, Alain Levine, Robert A. CA Leducq Transatlantic Mitral TI Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE echocardiography; endothelial-to-mesenchymal transition; inflammation; mitral regurgitation; papillary muscle ID GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; INTERSTITIAL-CELLS; HEART-FAILURE; TGF-BETA; 3-DIMENSIONAL ECHOCARDIOGRAPHY; COMPENSATORY MECHANISM; LEAFLET ADAPTATION; COLLAGEN-SYNTHESIS; CARDIAC FIBROSIS AB BACKGROUND In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that experimental tethering alone increases mitral valve area in association with endothelial-to-mesenchymal transition. OBJECTIVES The aim of this study was to explore the clinically relevant situation of tethering and MI, testing the hypothesis that ischemic milieu modifies mitral valve adaptation. METHODS Twenty-three adult sheep were examined. Under cardiopulmonary bypass, the papillary muscle tips in 6 sheep were retracted apically to replicate tethering, short of producing MR (tethered alone). Papillary muscle retraction was combined with apical MI created by coronary ligation in another 6 sheep (tethered plus MI), and left ventricular remodeling was limited by external constraint in 5 additional sheep (left ventricular constraint). Six sham-operated sheep were control subjects. Diastolic mitral valve surface area was quantified by 3-dimensional echocardiography at baseline and after 58 + 5 days, followed by histopathology and flow cytometry of excised leaflets. RESULTS Tethered plus MI leaflets were markedly thicker than tethered-alone valves and sham control subjects. Leaflet area also increased significantly. Endothelial-to-mesenchymal transition, detected as alpha-smooth muscle actin-positive endothelial cells, significantly exceeded that in tethered-alone and control valves. Transforming growth factor-beta, matrix metalloproteinase expression, and cellular proliferation were markedly increased. Uniquely, tethering plus MI showed endothelial activation with vascular adhesion molecule expression, neovascularization, and cells positive for CD45, considered a hematopoietic cell marker. Tethered plus MI findings were comparable with external ventricular constraint. CONCLUSIONS MI altered leaflet adaptation, including a profibrotic increase in valvular cell activation, CD45-positive cells, and matrix turnover. Understanding cellular and molecular mechanisms underlying leaflet adaptation and fibrosis could yield new therapeutic opportunities for reducing ischemic MR. (C) 2016 by the American College of Cardiology Foundation. C1 [Dal-Bianco, Jacob P.; Beaudoin, Jonathan; Szymanski, Catherine; Bartko, Philipp E.; Handschumacher, Mark D.; Chaput, Miguel; Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. [Guerrero, J. Luis; Seybolt, Margo M.; Sullivan, Suzanne; Garcia, Michael L.; Mauskapf, Adam; Titus, James S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Cardiovasc Lab, Boston, MA USA. [Dal-Bianco, Jacob P.; Aikawa, Elena; Bischoff, Joyce; Beaudoin, Jonathan; Szymanski, Catherine; Chaput, Miguel; Messas, Emmanuel; Hagege, Albert A.; Carpentier, Alain; Levine, Robert A.] Fdn Leducq, Leducq Transatlant Mitral Network, Paris, France. [Aikawa, Elena; Hjortnaes, Jesper; Irvin, Whitney S.] Brigham & Womens Hosp, Dept Med, Ctr Excellence Vasc Biol, Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. [Aikawa, Elena; Bischoff, Joyce; Hjortnaes, Jesper; Wylie-Sears, Jill; Irvin, Whitney S.] Harvard Univ, Sch Med, Boston, MA USA. [Bischoff, Joyce; Wylie-Sears, Jill] Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA. [Bischoff, Joyce] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Messas, Emmanuel; Hagege, Albert A.; Carpentier, Alain; Levine, Robert A.] Univ Paris 05, Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, INSERM,U633,Dept Cardiol, Paris, France. [Messas, Emmanuel; Hagege, Albert A.; Carpentier, Alain; Levine, Robert A.] Univ Paris 05, Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, INSERM,U633,Dept Cardiovasc Surg, Paris, France. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5068, Boston, MA 02114 USA. EM rlevine@partners.org OI Bischoff, Joyce/0000-0002-6367-1974 FU Fondation Leducq (Paris, France) [07CVD04]; National Heart, Lung, and Blood Institute of the National Institutes of Health [R01HL109506]; National Institutes of Health [K24 HL67434]; American Society of Echocardiography Career Development Award; Erwin-Schrodinger Stipend (FWF Austrian Science Fund); Harvard University, affiliated academic health care centers; Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health award) [UL1 TR001102] FX This work was supported in part by grant 07CVD04 from Fondation Leducq (Paris, France) for the Transatlantic MITRAL Network of Excellence and by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R01HL109506 to Drs. Levine, Aikawa, and Bischoff. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was from grant K24 HL67434 from the National Institutes of Health, an American Society of Echocardiography Career Development Award, and an Erwin-Schrodinger Stipend (FWF Austrian Science Fund). The biostatistical work was conducted with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health award UL1 TR001102), and financial contributions from Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic health care centers or the National Institutes of Health. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Dal-Bianco, Aikawa, and Bischoff contributed equally to this work. NR 49 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 26 PY 2016 VL 67 IS 3 BP 275 EP 287 DI 10.1016/j.jacc.2015.10.092 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB5NM UT WOS:000368560900007 PM 26796392 ER PT J AU Olabisi, OA Zhang, JY VerPlank, L Zahler, N DiBartolo, S Heneghan, JF Schlondorff, JS Suh, JH Yan, P Alper, SL Friedman, DJ Pollak, MR AF Olabisi, Opeyemi A. Zhang, Jia-Yue VerPlank, Lynn Zahler, Nathan DiBartolo, Salvatore, III Heneghan, John F. Schloendorff, Johannes S. Suh, Jung Hee Yan, Paul Alper, Seth L. Friedman, David J. Pollak, Martin R. TI APOL1 kidney disease risk variants cause cytotoxicity by depleting cellular potassium and inducing stress-activated protein kinases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apolipoprotein L1; kidney; African-American; genetics; protein kinase ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; HIV-ASSOCIATED NEPHROPATHY; TRYPANOSOME LYTIC FACTOR; LIPID-BINDING PROTEIN; APOLIPOPROTEIN L1; NEPHROTIC SYNDROME; RENAL-DISEASE; HUMAN SERUM; P38; PODOCYTE AB Two specific genetic variants of the apolipoprotein L1 (APOL1) gene are responsible for the high rate of kidney disease in people of recent African ancestry. Expression in cultured cells of these APOL1 risk variants, commonly referred to as G1 and G2, results in significant cytotoxicity. The underlying mechanism of this cytotoxicity is poorly understood. We hypothesized that this cytotoxicity is mediated by APOL1 risk variant-induced dysregulation of intracellular signaling relevant for cell survival. To test this hypothesis, we conditionally expressed WT human APOL1 (G0), the APOL1 G1 variant, or the APOL1 G2 variant in human embryonic kidney cells (T-REx-293) using a tetracycline-mediated (Tet-On) system. We found that expression of either G1 or G2 APOL1 variants increased apparent cell swelling and cell death compared with G0-expressing cells. These manifestations of cytotoxicity were preceded by G1 or G2 APOL1-induced net efflux of intracellular potassium as measured by X-ray fluorescence, resulting in the activation of stress-activated protein kinases (SAPKs), p38 MAPK, and JNK. Prevention of net K+ efflux inhibited activation of these SAPKs by APOL1 G1 or G2. Furthermore, inhibition of SAPK signaling and inhibition of net K+ efflux abrogated cytotoxicity associated with expression of APOL1 risk variants. These findings in cell culture raise the possibility that nephrotoxicity of APOL1 risk variants may be mediated by APOL1 risk variant-induced net loss of intracellular K+ and subsequent induction of stress-activated protein kinase pathways. C1 [Olabisi, Opeyemi A.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Olabisi, Opeyemi A.; Zhang, Jia-Yue; DiBartolo, Salvatore, III; Heneghan, John F.; Schloendorff, Johannes S.; Suh, Jung Hee; Yan, Paul; Alper, Seth L.; Friedman, David J.; Pollak, Martin R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Olabisi, Opeyemi A.; Zhang, Jia-Yue; Heneghan, John F.; Schloendorff, Johannes S.; Suh, Jung Hee; Yan, Paul; Alper, Seth L.; Friedman, David J.; Pollak, Martin R.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [VerPlank, Lynn; Zahler, Nathan] Icagen Inc, Durham, NC 27703 USA. [Heneghan, John F.; Alper, Seth L.; Friedman, David J.] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USA. RP Pollak, MR (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. EM mpollak@bidmc.harvard.edu FU NIH [MD007898, MD007092, T32-DK007199, T32-DK07540]; NephCure Foundation; Ellison Foundation FX We thank Anna Besschetnova and Chi-Wing Chow for help and advice. This work was supported by NIH Grants MD007898 and MD007092 (to M.R.P, D.J.F., and S.L.A.), as well as by grants from the NephCure and Ellison Foundations (to M.R.P.). O.A.O. and J.H.S. were supported in part by NIH Grant T32-DK007199. O.A.O. was also supported by NIH Grant T32-DK07540. NR 59 TC 14 Z9 15 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 26 PY 2016 VL 113 IS 4 BP 830 EP 837 DI 10.1073/pnas.1522913113 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB6IJ UT WOS:000368617900024 PM 26699492 ER PT J AU Krienen, FM Yeo, BTT Ge, T Buckner, RL Sherwood, CC AF Krienen, Fenna M. Yeo, B. T. Thomas Ge, Tian Buckner, Randy L. Sherwood, Chet C. TI Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE corticocortical connectivity; human transcriptome; association cortex; supragranular; brain evolution ID INTRINSIC FUNCTIONAL CONNECTIVITY; ADULT HUMAN BRAIN; GAMMA-SYNUCLEIN; PYRAMIDAL CELL; MACAQUE MONKEY; CEREBRAL-CORTEX; RHESUS-MONKEY; EVOLUTION; EXPRESSION; NEOCORTEX AB The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anti-correlated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections. C1 [Krienen, Fenna M.; Sherwood, Chet C.] George Washington Univ, Ctr Adv Study Human Paleobiol, Dept Anthropol, Washington, DC 20052 USA. [Krienen, Fenna M.; Sherwood, Chet C.] George Washington Univ, Inst Neurosci, Washington, DC 20052 USA. [Yeo, B. T. Thomas] Natl Univ Singapore, Singapore Inst Neurotechnol, Clin Imaging Res Ctr, Dept Elect & Comp Engn, Singapore 117583, Singapore. [Yeo, B. T. Thomas] Natl Univ Singapore, Memory Networks Program, Singapore 117583, Singapore. [Yeo, B. T. Thomas; Ge, Tian; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ge, Tian] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Krienen, Fenna M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Krienen, FM (reprint author), George Washington Univ, Ctr Adv Study Human Paleobiol, Dept Anthropol, Washington, DC 20052 USA.; Krienen, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM fenna_krienen@hms.harvard.edu OI Yeo, B.T. Thomas/0000-0002-0119-3276 FU Center for Brain Science Neuroinformatics Research Group; Athinoula A. Martinos Center for Biomedical Imaging; Center for Human Genetics Research; George Washington University Centers and Institute's Facilitating Fund Intramural Award; Singapore MOE Tier 2 [MOE2014-T2-2-016]; National University of Singapore Strategic Research Grant [DPRT/944/09/14]; National University of Singapore School of Medicine [R185000271720]; Singapore National Medical Research Council [CBRG14nov007, NMRC/CG/013/2013]; National University of Singapore Young Investigator Award; James S. McDonnell Foundation [220020293]; Massachusetts General Hospital Executive Committee on Research Tosteson Postdoctoral Fellowship award; Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital [1S10RR023401, 1S10RR019307, 1S10RR023043]; National University of Singapore Tier 1 FX We thank Steven McCarroll and Arpiar Saunders for helpful discussions. Data were provided (in part) by the Brain Genomics Superstruct Project of Harvard University and Massachusetts General Hospital, (Principal Investigators: R.L.B., Joshua Roffman, and Jordan Smoller), with support from the Center for Brain Science Neuroinformatics Research Group, the Athinoula A. Martinos Center for Biomedical Imaging, and the Center for Human Genetics Research. This work was supported by a George Washington University Centers and Institute's Facilitating Fund Intramural Award to the Mind-Brain Institute; National University of Singapore Tier 1, Singapore MOE Tier 2 (MOE2014-T2-2-016); National University of Singapore Strategic Research Grant DPRT/944/09/14; National University of Singapore School of Medicine Grant R185000271720; Singapore National Medical Research Council CBRG14nov007, NMRC/CG/013/2013, National University of Singapore Young Investigator Award; the James S. McDonnell Foundation (220020293); and a Massachusetts General Hospital Executive Committee on Research Tosteson Postdoctoral Fellowship award (to T.G.). This research also used resources provided by the Center for Functional Neuroimaging Technologies (P41EB015896), and instruments supported by Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043 from the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital. NR 77 TC 4 Z9 4 U1 4 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 26 PY 2016 VL 113 IS 4 BP E469 EP E478 DI 10.1073/pnas.1510903113 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB6IJ UT WOS:000368617900011 PM 26739559 ER PT J AU Glabska, HT Norheim, E Devor, A Dale, AM Einevoll, GT Wojcik, DK AF Glabska, Helena T. Norheim, Eivind Devor, Anna Dale, Anders M. Einevoll, Gaute T. Wojcik, Daniel K. TI Generalized Laminar Population Analysis (gLPA) for Interpretation of Multielectrode Data from Cortex SO FRONTIERS IN NEUROINFORMATICS LA English DT Article DE LFP analysis; local field potential (LFP); model-based analysis; signal decomposition; computational neuroscience; multi-unit activity; MUA; thalamocortical ID CURRENT-SOURCE-DENSITY; INDEPENDENT COMPONENT ANALYSIS; FIELD POTENTIALS; FIRING RATES; RECORDINGS; MODEL; DYNAMICS; SPIKES; EEG AB Laminar population analysis (LPA) is a method for analysis of electrical data recorded by linear multielectrodes passing through all lamina of cortex. Like principal components analysis (PCA) and independent components analysis (ICA), LPA offers a way to decompose the data into contributions from separate cortical populations. However, instead of using purely mathematical assumptions in the decomposition, LPA is based on physiological constraints, i.e., that the observed LFP (low-frequency part of signal) is driven by action-potential firing as observed in the MUA (multi-unit activity; high-frequency part of the signal). In the presently developed generalized laminar population analysis (gLPA) the set of basis functions accounting for the LFP data is extended compared to the original LPA, thus allowing for a better fit of the model to experimental data. This enhances the risk for overfitting, however, and we therefore tested various versions of gLPA on virtual LFP data in which we knew the ground truth. These synthetic data were generated by biophysical forward-modeling of electrical signals from network activity in the comprehensive, and well-known, thalamocortical network model developed by Traub and coworkers. The results for the Traub model imply that while the laminar components extracted by the original LPA method overall are in fair agreement with the ground-truth laminar components, the results may be improved by use of gLPA method with two (gLPA-2) or even three (gLPA-3) postsynaptic LFP kernels per laminar population. C1 [Glabska, Helena T.; Wojcik, Daniel K.] Polish Acad Sci, M Nencki Inst Expt Biol, Dept Neurophysiol, Lab Neuroinformat, Warsaw, Poland. [Norheim, Eivind; Einevoll, Gaute T.] Norwegian Univ Life Sci, Dept Math Sci & Technol, As, Norway. [Devor, Anna; Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Devor, Anna; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Devor, Anna] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Einevoll, Gaute T.] Univ Oslo, Dept Phys, Oslo, Norway. RP Wojcik, DK (reprint author), Polish Acad Sci, M Nencki Inst Expt Biol, Dept Neurophysiol, Lab Neuroinformat, Warsaw, Poland.; Einevoll, GT (reprint author), Norwegian Univ Life Sci, Dept Math Sci & Technol, As, Norway.; Einevoll, GT (reprint author), Univ Oslo, Dept Phys, Oslo, Norway. EM gaute.einevoll@nmbu.no; d.wojcik@nencki.gov.pl RI Wojcik, Daniel/C-6334-2008 OI Wojcik, Daniel/0000-0003-0812-9872 FU EC [269921]; Polish Ministry for Science and Higher Education [5428/B/P01/2010/39, 2948/7.PR/2013/2]; Polish Ministry of Regional Development [POIG.02.03.00-00-003/09, POIG.02.03.00-00-018/08] FX This work is supported by the EC-EP7 under grant agreement no. 269921 ("BrainScaleS"), and the Polish Ministry for Science and Higher Education (grants 5428/B/P01/2010/39 and 2948/7.PR/2013/2), the Polish Ministry of Regional Development (grant POIG.02.03.00-00-003/09, POIG.02.03.00-00-018/08). NR 39 TC 1 Z9 1 U1 2 U2 6 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5196 J9 FRONT NEUROINFORM JI Front. Neuroinformatics PD JAN 25 PY 2016 VL 10 AR 1 DI 10.3389/fninf.2016.00001 PG 15 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA DE4QA UT WOS:000370613400001 PM 26834620 ER PT J AU Rasheed, H McKinney, C Stamp, LK Dalbeth, N Topless, RK Day, R Kannangara, D Williams, K Smith, M Janssen, M Jansen, TL Joosten, LA Radstake, TR Riches, PL Tausche, AK Liote, F Lu, L Stahl, EA Choi, HK So, A Merriman, TR AF Rasheed, Humaira McKinney, Cushla Stamp, Lisa K. Dalbeth, Nicola Topless, Ruth K. Day, Richard Kannangara, Diluk Williams, Kenneth Smith, Malcolm Janssen, Matthijs Jansen, Tim L. Joosten, Leo A. Radstake, Timothy R. Riches, Philip L. Tausche, Anne-Kathrin Liote, Frederic Lu, Leo Stahl, Eli A. Choi, Hyon K. So, Alexander Merriman, Tony R. TI The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets SO PLOS ONE LA English DT Article ID ASSOCIATION; DISEASE; SUSCEPTIBILITY; POLYMORPHISMS; ARTHRITIS; GENE AB Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-kappa B signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism rs2149356 in TLR4 is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Maori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, P = 0.012) and decreased the risk of gout in Polynesians (OR = 0.80, P = 0.011). There was no evidence for association in the HPFS or NHS sample sets. In conclusion TLR4 SNP rs2143956 associates with gout risk in prevalent clinically-ascertained gout in Europeans, in a direction consistent with previously published results in Han Chinese. However, with an opposite direction of association in Polynesians and no evidence for association in a non-clinically-ascertained incident gout cohort this variant should be analysed in other international gout genetic data sets to determine if there is genuine evidence for association. C1 [Rasheed, Humaira; McKinney, Cushla; Topless, Ruth K.; Merriman, Tony R.] Univ Otago, Dept Biochem, Dunedin, New Zealand. [Rasheed, Humaira] Univ Engn & Technol, Lahore, Pakistan. [Stamp, Lisa K.] Univ Otago, Dept Med, Christchurch, New Zealand. [Dalbeth, Nicola] Univ Auckland, Dept Med, Auckland 1, New Zealand. [Day, Richard; Kannangara, Diluk; Williams, Kenneth] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia. [Day, Richard; Kannangara, Diluk; Williams, Kenneth] St Vincents Hosp, Dept Clin Pharmacol & Toxicol, Sydney, NSW 2010, Australia. [Smith, Malcolm] Flinders Med Ctr, Dept Med, Adelaide, SA, Australia. [Smith, Malcolm] Repatriat Gen Hosp, Adelaide, SA, Australia. [Janssen, Matthijs] Rijnstate Hosp, Dept Rheumatol, Arnhem, Netherlands. [Jansen, Tim L.] VieCuri Med Ctr, Dept IQ HealthCare, Venlo, Netherlands. [Joosten, Leo A.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands. [Joosten, Leo A.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, NL-6525 ED Nijmegen, Netherlands. [Radstake, Timothy R.] Univ Med Ctr Utrecht, Dept Immunol, Lab Translat Immunol, Dept Rheumatol & Clin Immunol, Utrecht, Netherlands. [Riches, Philip L.] Univ Edinburgh, Inst Genet & Mol Med, Rheumat Dis Unit, Edinburgh, Midlothian, Scotland. [Tausche, Anne-Kathrin] Univ Clin Carl Gustav Carus, Dept Rheumatol, Dresden, Germany. [Liote, Frederic] Hosp Lariboisiere, INSERM, UMR S 1132, Paris, France. [Liote, Frederic] Univ Paris Diderot, Sorbonne Paris Cite, UFR Med, Paris, France. [Lu, Leo; Choi, Hyon K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Stahl, Eli A.] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. [So, Alexander] Univ Lausanne, Lab Rheumatol, Serv Rheumatol, DAL,CHUV, Lausanne, Switzerland. RP Merriman, TR (reprint author), Univ Otago, Dept Biochem, Dunedin, New Zealand. OI Kannangara, Diluk/0000-0003-1463-7320; Merriman, Tony/0000-0003-0844-8726 FU Health Research Council of New Zealand [11/1075, 14/527]; Arthritis New Zealand; New Zealand Lottery Health; University of Otago and Arthritis Australia; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, UL1RR025005]; NIH Roadmap for Medical Research; National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University; [N01-HC-55015]; [N01-HC-55016]; [N01-HC-55018]; [N01-HC-55019]; [N01-HC55020]; [N01-HC-55021]; [N01-HC-55022]; [R01HL087641]; [R01HL59367]; [R01HL086694] FX This work was supported by the Health Research Council of New Zealand (11/1075, 14/527), Arthritis New Zealand, New Zealand Lottery Health, the University of Otago and Arthritis Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Atherosclerosis Risk in Communities study is supported by contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The Framingham Heart Study and the Framingham SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University. NR 24 TC 1 Z9 1 U1 3 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 25 PY 2016 VL 11 IS 1 AR e0147939 DI 10.1371/journal.pone.0147939 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC9FZ UT WOS:000369527800247 PM 26808548 ER PT J AU Cadoni, S Liggi, M Falt, P Sanna, S Argiolas, M Fanari, V Gallittu, P Mura, D Porcedda, ML Smajstrla, V Erriu, M Leung, FW AF Cadoni, Sergio Liggi, Mauro Falt, Premysl Sanna, Stefano Argiolas, Mariangela Fanari, Viviana Gallittu, Paolo Mura, Donatella Porcedda, Maria L. Smajstrla, Vit Erriu, Matteo Leung, Felix W. TI Evidence to suggest adoption of water exchange deserves broader consideration: Its pain alleviating impact occurs in 90% of investigators SO WORLD JOURNAL OF GASTROINTESTINAL ENDOSCOPY LA English DT Article DE Colonoscopy; Painless colonoscopy; Water immersion; Water exchange; Colonoscopy pain ID IRRITABLE-BOWEL-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; UNSEDATED COLONOSCOPY; AIDED COLONOSCOPY; AIR INSUFFLATION; PERCEPTION; DIFFICULTY; IMMERSION; ENDOSCOPY; SEDATION AB AIM: To determine variations in colonoscopy real-time insertion pain among investigators using three different insertion techniques. METHODS: From March 2013 through June 2014, 18-85-year-old diagnostic and 50-70-year-old screening patients were enrolled at each center to on-demand sedation colonoscopy with water exchange (WE), water immersion (WI) and insufflation with air or CO2 for insertion and withdrawal [air or carbon dioxide (AICD)]. Data were aggregated for analysis. Primary outcome: Variations in real-time maximum insertion pain (0 = none, 1-2 = discomfort, 10 = worst). RESULTS: One thousand and ninety-one cases analyzed: WE (n = 371); WI (n = 338); AICD (n = 382). Demographics and indications were comparable. The WE group had the lowest real-time maximum insertion pain score, mean (95% CI): WE 2.8 (2.6-3.0), WI 3.8 (3.5-4.1) and AICD 4.4 (4.1-4.7), P < 0.0005. Ninety percent of the colonoscopists were able to use water exchange to significantly decrease maximum insertion pain scores. One investigator had high insertion pain in all groups, nonetheless WE achieved the lowest real-time maximum insertion pain score. WE had the highest proportions of patients with painless unsedated colonoscopy (vs WI, P = 0.013; vs AICD, P < 0.0005); unsedated colonoscopy with only minor discomfort (vs AICD, P < 0.0005), and completion without sedation (vs AICD, P < 0.0005). CONCLUSION: Aggregate data confirm superiority of WE in lowering colonoscopy real-time maximum insertion pain and need for sedation. Ninety percent of investigators were able to use water exchange to significantly decrease maximum insertion pain scores. Our results suggest that the technique deserves consideration in a broader scale. C1 [Cadoni, Sergio; Liggi, Mauro; Gallittu, Paolo; Mura, Donatella] St Barbara Hosp, Digest Endoscopy Unit, Via San Leonardo 1, I-09016 Iglesias, Italy. [Falt, Premysl; Smajstrla, Vit] Vitkovice Hosp, Ctr Digest Dis, Ostrava 70384, Czech Republic. [Sanna, Stefano; Argiolas, Mariangela; Fanari, Viviana; Porcedda, Maria L.] NS di Bonaria Hosp, Digest Endoscopy Unit, I-09037 San Gavino Monreale, Italy. [Erriu, Matteo] Univ Cagliari, Dept Surg Sci, I-09121 Cagliari, Italy. [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA 91343 USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Cadoni, S (reprint author), St Barbara Hosp, Digest Endoscopy Unit, Via San Leonardo 1, I-09016 Iglesias, Italy. EM cadonisergio@gmail.com NR 40 TC 0 Z9 0 U1 0 U2 2 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1948-5190 J9 WORLD J GASTROINTEST JI World J. Gastrointest. Endosc. PD JAN 25 PY 2016 VL 8 IS 2 BP 113 EP 121 DI 10.4253/wjge.v8.i2.113 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DD1UM UT WOS:000369707500008 PM 26839651 ER PT J AU Belkind-Gerson, J Hotta, R Whalen, M Nayyar, N Nagy, N Cheng, L Zuckerman, A Goldstein, AM Dietrich, J AF Belkind-Gerson, Jaime Hotta, Ryo Whalen, Michael Nayyar, Naema Nagy, Nandor Cheng, Lily Zuckerman, Aaron Goldstein, Allan M. Dietrich, Jorg TI Engraftment of enteric neural progenitor cells into the injured adult brain SO BMC NEUROSCIENCE LA English DT Article DE Enteric neuronal progenitor cells; Stem cells; Brain injury; Cell transplantation; Brain repair ID STEM-CELLS; HIPPOCAMPAL NEUROGENESIS; NERVOUS-SYSTEM; EUROPE 2010; NEURONS; DISORDERS; DISEASE; MOUSE; MICE; GUT AB Background: A major area of unmet need is the development of strategies to restore neuronal network systems and to recover brain function in patients with neurological disease. The use of cell-based therapies remains an attractive approach, but its application has been challenging due to the lack of suitable cell sources, ethical concerns, and immune-mediated tissue rejection. We propose an innovative approach that utilizes gut-derived neural tissue for cell-based therapies following focal or diffuse central nervous system injury. Results: Enteric neuronal stem and progenitor cells, able to differentiate into neuronal and glial lineages, were isolated from the postnatal enteric nervous system and propagated in vitro. Gut-derived neural progenitors, genetically engineered to express fluorescent proteins, were transplanted into the injured brain of adult mice. Using different models of brain injury in combination with either local or systemic cell delivery, we show that transplanted enteric neuronal progenitor cells survive, proliferate, and differentiate into neuronal and glial lineages in vivo. Moreover, transplanted cells migrate extensively along neuronal pathways and appear to modulate the local microenvironment to stimulate endogenous neurogenesis. Conclusions: Our findings suggest that enteric nervous system derived cells represent a potential source for tissue regeneration in the central nervous system. Further studies are needed to validate these findings and to explore whether autologous gut-derived cell transplantation into the injured brain can result in functional neurologic recovery. C1 [Belkind-Gerson, Jaime; Whalen, Michael] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hotta, Ryo; Nagy, Nandor; Cheng, Lily; Zuckerman, Aaron; Goldstein, Allan M.] Harvard Univ, Sch Med, Dept Pediat Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nayyar, Naema; Dietrich, Jorg] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Div Neurooncol, Boston, MA 02114 USA. [Nayyar, Naema; Dietrich, Jorg] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Belkind-Gerson, Jaime; Goldstein, Allan M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Neurogastroenterol Program, 175 Cambridge St 575, Boston, MA 02114 USA. RP Belkind-Gerson, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Neurogastroenterol Program, 175 Cambridge St 575, Boston, MA 02114 USA. EM jbelkindgerson@mgh.harvard.edu NR 36 TC 1 Z9 1 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD JAN 25 PY 2016 VL 17 AR 5 DI 10.1186/s12868-016-0238-y PG 11 WC Neurosciences SC Neurosciences & Neurology GA DC4BM UT WOS:000369164800001 PM 26810757 ER PT J AU Rajagopal, J Stanger, BZ AF Rajagopal, Jayaraj Stanger, Ben Z. TI Plasticity in the Adult: How Should the Waddington Diagram Be Applied to Regenerating Tissues? SO DEVELOPMENTAL CELL LA English DT Review ID STEM-CELLS; DROSOPHILA TESTIS; EPITHELIAL-CELLS; BETA-CELLS; IN-VIVO; DEDIFFERENTIATION; NICHE; CONVERSION; OCCURS; AGE AB Conrad Waddington's eponymous 1957 diagram provided a metaphorical framework for considering how sequential developmental fate decisions allow an egg to develop into an embryo. In recent years, the Waddington diagram has been repurposed to illustrate how cellular identity changes in the context of reprogramming. In this Perspective, we revisit the Waddington diagram in light of the emerging recognition that plasticity is part and parcel of adult regeneration. Specifically, we speculate that the "epigenetic landscapes" that define identity in adult tissues are dynamic, facilitating cellular de-differentiation and trans-differentiation in the setting of injury. C1 [Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Rajagopal, Jayaraj] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Dept Med, Boston, MA 02114 USA. [Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Inst Regenerat Med, Dept Med, Philadelphia, PA 19104 USA. [Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Inst Regenerat Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. RP Rajagopal, J (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA.; Rajagopal, J (reprint author), Massachusetts Gen Hosp, Harvard Stem Cell Inst, Dept Med, Boston, MA 02114 USA.; Stanger, BZ (reprint author), Univ Penn, Perelman Sch Med, Inst Regenerat Med, Dept Med, Philadelphia, PA 19104 USA.; Stanger, BZ (reprint author), Univ Penn, Perelman Sch Med, Inst Regenerat Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. EM jrajagopal@mgh.harvard.edu; bstanger@exchange.upenn.edu NR 19 TC 4 Z9 4 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD JAN 25 PY 2016 VL 36 IS 2 BP 133 EP 137 DI 10.1016/j.devcel.2015.12.021 PG 5 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA DC6TV UT WOS:000369353400004 PM 26812013 ER PT J AU Penney, LS Ritenbaugh, C Elder, C Schneider, J Deyo, RA DeBar, LL AF Penney, Lauren S. Ritenbaugh, Cheryl Elder, Charles Schneider, Jennifer Deyo, Richard A. DeBar, Lynn L. TI Primary care physicians, acupuncture and chiropractic clinicians, and chronic pain patients: a qualitative analysis of communication and care coordination patterns SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article DE Chronic musculoskeletal pain; Complementary and alternative medicine; Managed care system; Interprofessional communication; Chronic care; Acupuncture; Chiropractic ID LOW-BACK-PAIN; ALTERNATIVE MEDICINE; HEALTH-CARE; COMPLEMENTARY PRACTITIONERS; RANDOMIZED-TRIAL; OLDER PATIENTS; INTEGRATION; MANIPULATION; PREVALENCE; CHALLENGE AB Background: A variety of people, with multiple perspectives, make up the system comprising chronic musculoskeletal pain (CMP) treatment. While there are frequently problems in communication and coordination of care within conventional health systems, more opportunities for communicative disruptions seem possible when providers use different explanatory models and are not within the same health management system. We sought to describe the communication system surrounding the management of chronic pain from the perspectives of allopathic providers, acupuncture and chiropractor (A/C) providers, and CMP patients. Methods: We collected qualitative data from CMP patients (n = 90) and primary care physicians (PCPs) (n = 25) in a managed care system, and community acupuncture and chiropractic care providers (n = 14) who received high levels of referrals from the system, in the context of a longitudinal study of CMP patients' experience. Results: Multiple points of divergence and communicative barriers were identified among the main stakeholders in the system. Those that were most frequently mentioned included issues surrounding the referral process (requesting, approving) and lack of consistent information flow back to providers that impairs overall management of patient care. We found that because of these problems, CMP patients were frequently tasked and sometimes overwhelmed with integrating and coordinating their own care, with little help from the system. Conclusions: Patients, PCPs, and A/C providers desire more communication; thus systems need to be created to facilitate more open communication which could positively benefit patient outcomes. C1 [Penney, Lauren S.] South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. [Ritenbaugh, Cheryl] Univ Arizona, Dept Family & Community Med, 1450 N Cherry Ave, Tucson, AZ 85719 USA. [Elder, Charles; Schneider, Jennifer; DeBar, Lynn L.] Kaiser Permanente Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Mail Code FM,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. RP DeBar, LL (reprint author), Kaiser Permanente Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA. EM lynn.debar@kpchr.org FU National Institutes of Health, National Center for Complementary and Alternative Medicine Grant [R01 AT005896] FX The authors gratefully acknowledge that our study received funding support from the National Institutes of Health, National Center for Complementary and Alternative Medicine Grant (R01 AT005896). NR 44 TC 0 Z9 0 U1 2 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6882 J9 BMC COMPLEM ALTERN M JI BMC Complement. Altern. Med. PD JAN 25 PY 2016 VL 16 AR 30 DI 10.1186/s12906-016-1005-4 PG 11 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DB9ZO UT WOS:000368876600002 PM 26810302 ER PT J AU Liu, X Mao, K Yu, AYH Omairi-Nasser, A Austin, J Glick, BS Yip, CK Klionsky, DJ AF Liu, Xu Mao, Kai Yu, Angela Y. H. Omairi-Nasser, Amin Austin, Jotham, II Glick, Benjamin S. Yip, Calvin K. Klionsky, Daniel J. TI The Atg17-Atg31-Atg29 Complex Coordinates with Atg11 to Recruit the Vam7 SNARE and Mediate Autophagosome-Vacuole Fusion SO CURRENT BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; TARGETING PATHWAY; YEAST; TRANSPORT; PROTEINS; ADAPTATIONS; BIOGENESIS; DROSOPHILA; MACHINERY; CLEARANCE AB Macroautophagy (hereafter autophagy) is an evolutionarily conserved process in which portions of the cytoplasm are engulfed, degraded, and subsequently recycled. The Atg17-Atg31-Atg29 complex translocates to the phagophore assembly site (PAS), where an autophagosome forms, at a very early stage of autophagy, playing a vital role in autophagy induction. Here, we identified a novel role of this complex in a late stage of autophagy where it coordinates with Atg11 to regulate autophagy-specific fusion with the vacuole. Atg17 and Atg11 interact with the vacuolar SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) Vam7 independently of each other. Several hydrophobic residues in helix 1 and helix 4 of Atg17 and the SNARE domain of Vam7 mediate the Atg17-Vam7 interaction. An F317D mutation of Atgl 7, which diminishes its interaction with Vam7 without affecting its interaction with Atg13 or Atg31, leads to a defect in the fusion of autophagosomes with the vacuole and decreased autophagy activity. These results provide the first demonstration that the Atg17-Atg31-Atg29 complex functions in both early and late stages of autophagy and also provide a mechanistic explanation for the coordination of autophagosome completion and fusion with the vacuole. C1 [Liu, Xu; Mao, Kai; Klionsky, Daniel J.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Liu, Xu; Mao, Kai; Klionsky, Daniel J.] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. [Yu, Angela Y. H.; Yip, Calvin K.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada. [Omairi-Nasser, Amin; Glick, Benjamin S.] Univ Chicago, Dept Mol Genet & Cell Biol, 920 E 58Th St, Chicago, IL 60637 USA. [Austin, Jotham, II] Univ Chicago, Electron Microscopy Core Facil, Chicago, IL 60637 USA. [Mao, Kai] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. [Mao, Kai] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Klionsky, DJ (reprint author), Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.; Klionsky, DJ (reprint author), Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. EM klionsky@umich.edu FU NIH [GM053396, P30 CA014599]; Canadian Institutes of Health Research [MOP-126126]; University of British Columbia; Biological Systems Science Division, Office of Biological and Environmental Research, Office of Science, US Department of Energy [DE-AC02-06CH11357] FX This work was supported by NIH grant GM053396 to D.J.K.; an operating grant from the Canadian Institutes of Health Research (MOP-126126) and startup funds from the University of British Columbia to C.K.Y.; and funding through the Biological Systems Science Division, Office of Biological and Environmental Research, Office of Science, US Department of Energy, under contract DE-AC02-06CH11357 with B.S.G. Fluorescence microscopy was performed at the Integrated Microscopy Core Facility, and electron microscopy was performed at the Electron Microscopy Core Facility, with support for both facilities coming from the NIH-funded Cancer Center Support Grant P30 CA014599. NR 47 TC 7 Z9 7 U1 3 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD JAN 25 PY 2016 VL 26 IS 2 BP 150 EP 160 DI 10.1016/j.cub.2015.11.054 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DC1JJ UT WOS:000368972300017 PM 26774783 ER PT J AU Hazan, R Que, YA Maura, D Strobel, B Majcherczyk, PA Hopper, LR Wilbur, DJ Hreha, TN Barquera, B Rahme, LG AF Hazan, Ronen Que, Yok Ai Maura, Damien Strobel, Benjamin Majcherczyk, Paul Anthony Hopper, Laura Rose Wilbur, David J. Hreha, Teri N. Barquera, Blanca Rahme, Laurence G. TI Auto Poisoning of the Respiratory Chain by a Quorum-Sensing-Regulated Molecule Favors Biofilm Formation and Antibiotic Tolerance SO CURRENT BIOLOGY LA English DT Article ID MEDIATED CELL-DEATH; PSEUDOMONAS-AERUGINOSA; PERMEABILITY TRANSITION; ESCHERICHIA-COLI; RHODOBACTER-SPHAEROIDES; BACTERIAL BIOFILMS; LYSIS; MECHANISM; APOPTOSIS; MUTANTS AB Bacterial programmed cell death and quorum sensing are direct examples of prokaryote group behaviors, wherein cells coordinate their actions to function cooperatively like one organism for the benefit of the whole culture. We demonstrate here that 2-n-heptyl--hydroxyquinoline-N-oxide (HQNO), a Pseudomonas aeruginosa quorum-sensing-regulated low-molecular-weight excreted molecule, triggers autolysis by self-perturbing the electron transfer reactions of the cytochrome bc(1) complex. HQNO induces specific self-poisoning by disrupting the flow of electrons through the respiratory chain at the cytochrome bc(1) complex, causing a leak of reducing equivalents to O-2 whereby electrons that would normally be passed to cytochrome c are donated directly to O-2. The subsequent mass production of reactive oxygen species (ROS) reduces membrane potential and disrupts membrane integrity, causing bacterial cell autolysis and DNA release. DNA subsequently promotes biofilm formation and increases antibiotic tolerance to beta-actams, suggesting that HQNO-dependent cell autolysis is advantageous to the bacterial populations. These data identify both a new programmed cell death system and a novel role for HQNO as a critical inducer of biofilm formation and antibiotic tolerance. This newly identified pathway suggests intriguing mechanistic similarities with the initial mitochondrial-mediated steps of eukaryotic apoptosis. C1 [Hazan, Ronen; Que, Yok Ai; Maura, Damien; Strobel, Benjamin; Hopper, Laura Rose; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Hazan, Ronen; Que, Yok Ai; Maura, Damien; Strobel, Benjamin; Hopper, Laura Rose; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Hazan, Ronen; Que, Yok Ai; Maura, Damien; Strobel, Benjamin; Hopper, Laura Rose; Rahme, Laurence G.] Massachusetts Gen Hosp, Ctr Surg Innovat & Bioengn, Dept Surg, Boston, MA 02114 USA. [Hazan, Ronen; Que, Yok Ai; Maura, Damien; Rahme, Laurence G.] Shriners Hosp Children Boston, Boston, MA 02114 USA. [Majcherczyk, Paul Anthony] Univ Lausanne, Dept Fundamental Microbiol, CH-1015 Lausanne, Switzerland. [Wilbur, David J.] Tufts Univ, Dept Chem, Medford, MA 02155 USA. [Hreha, Teri N.; Barquera, Blanca] Rensselaer Polytech Inst, CBIS, Dept Biol Sci, 110 8th St, Troy, NY 12180 USA. [Hazan, Ronen] Hebrew Univ Jerusalem, Inst Dent Sci, POB 12272, IL-91120 Jerusalem, Israel. [Hazan, Ronen] Hebrew Univ Jerusalem, Sch Dent Med, POB 12272, IL-91120 Jerusalem, Israel. [Que, Yok Ai] Univ Lausanne, Dept Fundamental Microbiol, CH-1015 Lausanne, Switzerland. RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.; Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.; Rahme, LG (reprint author), Massachusetts Gen Hosp, Ctr Surg Innovat & Bioengn, Dept Surg, Boston, MA 02114 USA.; Rahme, LG (reprint author), Shriners Hosp Children Boston, Boston, MA 02114 USA. EM rahme@molbio.mgh.harvard.edu FU research grants Shriners [8770]; Cystic Fibrosis Foundation [11P0]; NIAID [R33AI105902, R56AI063433]; Shriners Hospitals Research Fellowship [8494]; Swiss National Science Foundation/Swiss Medical Association (FMH) [PASMP3-123226]; SICPA Foundation; [NSF-MCB1052234] FX This work was supported by research grants Shriners #8770, Cystic Fibrosis Foundation #11P0, and NIAID R33AI105902 and R56AI063433 to L.G.R. R.H. was supported by Shriners Hospitals Research Fellowship #8494. Y.A.Q. was supported by Swiss National Science Foundation/Swiss Medical Association (FMH) grant #PASMP3-123226 and a grant from the SICPA Foundation. B.B. and T.N.H. were supported by research grant NSF-MCB1052234 to B.B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Drs. Scott Stachel and Alicia Ballok for the critical reading of this manuscript. This work is dedicated to the memory of Scott Stachel. NR 50 TC 4 Z9 4 U1 4 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD JAN 25 PY 2016 VL 26 IS 2 BP 195 EP 206 DI 10.1016/j.cub.2015.11.056 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DC1JJ UT WOS:000368972300021 PM 26776731 ER PT J AU Bai, JW Boulet, G Halpern, EM Lovblom, LE Eldelekli, D Keenan, HA Brent, M Paul, N Bril, V Cherney, DZI Weisman, A Perkins, BA AF Bai, Johnny W. Boulet, Genevieve Halpern, Elise M. Lovblom, Leif E. Eldelekli, Devrim Keenan, Hillary A. Brent, Michael Paul, Narinder Bril, Vera Cherney, David Z. I. Weisman, Alanna Perkins, Bruce A. TI Cardiovascular disease guideline adherence and self-reported statin use in longstanding type 1 diabetes: results from the Canadian study of longevity in diabetes cohort SO CARDIOVASCULAR DIABETOLOGY LA English DT Article DE Type 1 diabetes; Cardiovascular disease; HMG-CoA reductase inhibitor (3-hydroxy-3-methyl-glutaryl-CoA reductase); Statin; Adherence ID CORONARY-HEART-DISEASE; PRIMARY PREVENTION; CHOLESTEROL LEVELS; MORTALITY; POPULATION; DURATION; THERAPY; PEOPLE; COMPLICATIONS; NONADHERENCE AB Background: Older patients with longstanding type 1 diabetes have high cardiovascular disease (CVD) risk such that statin therapy is recommended independent of prior CVD events. We aimed to determine self-reported CVD prevention guideline adherence in patients with longstanding diabetes. Research design and methods: 309 Canadians with over 50 years of type 1 diabetes completed a medical questionnaire for presence of lifestyle and pharmacological interventions, stratified into primary or secondary CVD prevention subgroups based on absence or presence of self-reported CVD events, respectively. Associations with statin use were analyzed using multivariable logistic regression. Results: The 309 participants had mean +/- SD age 65.7 +/- 8.5 years, median diabetes duration 54.0 [IQR 51.0, 59.0] years, and HbA1c of 7.5 +/- 1.1 % (58 mmol/mol). 159 (52.7 %) participants reported diet adherence, 296 (95.8 %) smoking avoidance, 217 (70.5 %) physical activity, 218 (71.5 %) renin-angiotensin-system inhibitor use, and 220 (72.1 %) statin use. Physical activity was reported as less common in the secondary prevention subgroup, and current statin use was significantly lower in the primary prevention subgroup (65.5 % vs. 84.8 %, p = 0.0004). In multivariable logistic regression, the odds of statin use was 0.38 [95 % CI 0.15-0.95] in members of the primary compared to the secondary prevention subgroup, adjusting for age, sex, hypertension history, body mass, HbA1c, cholesterol, microvascular complications, acetylsalicylic acid use, and renin-angiotensin system inhibitor use. Conclusion: Despite good self-reported adherence to general CVD prevention guidelines, against the principles of these guidelines we found that statin use was substantially lower in those without CVD history. Interventions are needed to improve statin use in older type 1 diabetes patients without a history of CVD. C1 [Bai, Johnny W.; Boulet, Genevieve; Halpern, Elise M.; Lovblom, Leif E.; Eldelekli, Devrim; Weisman, Alanna; Perkins, Bruce A.] Univ Toronto, Mt Sinai Hosp, Div Endocrinol & Metab, Dept Med,Leadership Sinai Ctr Diabet, L5-210,60 Murray St,Mail Box 16, Toronto, ON M5T 3L9, Canada. [Keenan, Hillary A.] Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. [Brent, Michael] Univ Toronto, Dept Med, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada. [Paul, Narinder] Univ Hlth Network, Div Cardiothorac Radiol, Joint Dept Med Imaging, Toronto, ON, Canada. [Bril, Vera] Univ Toronto, Univ Hlth Network, Ellen & Martin Prosserman Ctr Neuromuscular Dis, Krembil Neurosci Ctr,Div Neurol,Dept Med, Toronto, ON, Canada. [Cherney, David Z. I.] Univ Toronto, Dept Med, Div Nephrol, Toronto, ON, Canada. RP Perkins, BA (reprint author), Univ Toronto, Mt Sinai Hosp, Div Endocrinol & Metab, Dept Med,Leadership Sinai Ctr Diabet, L5-210,60 Murray St,Mail Box 16, Toronto, ON M5T 3L9, Canada. EM BPerkins@mtsinai.on.ca FU University of Toronto CREMS Summer Research Program; JDRF Canadian Clinical Trial Network; Medtronic; Boehringer Ingelheim; AstraZeneca; Merck; Canadian Diabetes Association, JDRF Canada and its Canadian Clinical Trial Network FX JWB has received funding from the University of Toronto CREMS Summer Research Program and AW has received a post-doctoral fellowship award from the JDRF Canadian Clinical Trial Network. BAP has received speaker honoraria from Medtronic Inc., Johnson and Johnson, Roche, Glaxo Smith Kline Canada, Novo Nordisk and Sanofi; has received research grant support from Medtronic and Boehringer Ingelheim; and serves as a consultant for Neurometrix. DZIC has received speaker honoraria from Janssen, AstraZeneca, Boehringer Ingelheim, Lilly and Merck and has received research grant support from AstraZeneca, Merck and Boehringer Ingelheim. We are grateful to the Canadian Diabetes Association, JDRF Canada and its Canadian Clinical Trial Network for their support. NR 43 TC 2 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2840 J9 CARDIOVASC DIABETOL JI Cardiovasc. Diabetol. PD JAN 25 PY 2016 VL 15 AR 14 DI 10.1186/s12933-015-0318-9 PG 10 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism SC Cardiovascular System & Cardiology; Endocrinology & Metabolism GA DC0JG UT WOS:000368902400001 PM 26809442 ER PT J AU Miyazaki, Y Song, JW Takahashi, E AF Miyazaki, Yuta Song, Jae W. Takahashi, Emi TI Asymmetry of Radial and Symmetry of Tangential Neuronal Migration Pathways in Developing Human Fetal Brains SO FRONTIERS IN NEUROANATOMY LA English DT Article DE development; radial migration; ganglionic eminence; human; diffusion imaging; tractography ID HUMAN CEREBRAL-CORTEX; RESOLUTION DIFFUSION TRACTOGRAPHY; CORTICAL GABAERGIC NEURONS; X-LINKED MALFORMATIONS; HUMAN NEOCORTEX; WHITE-MATTER; TELENCEPHALIC ORIGIN; SUBVENTRICULAR ZONE; BIPOLAR DISORDER; BASAL FOREBRAIN AB The radial and tangential neural migration pathways are two major neuronal migration streams in humans that are critical during corticogenesis. Corticogenesis is a complex process of neuronal proliferation that is followed by neuronal migration and the formation of axonal connections. Existing histological assessments of these two neuronal migration pathways have limitations inherent to microscopic studies and are confined to small anatomic regions of interest (ROls). Thus, little evidence is available about their threedimensional (3-D) fiber pathways and development throughout the entire brain. In this study, we imaged and analyzed radial and tangential migration pathways in the whole human brain using high -angular resolution diffusion MR imaging (HARDI) tractography. We imaged ten fixed, postmortem fetal (17 gestational weeks ((3V@. 18 GW, 19 (lW, three 20 GW, three 21 GW and 22 GW) and eight in vivo newborn (two 30 GW, 34 GW, 35 GW and four 40 Gq brains with no neurological/pathological conditions. We statistically compared the volume of the left and right radial and tangential migration pathways, and the volume of the radial migration pathways of the anterior and posterior regions of the brain. In specimens 22 GW or younger, the volume of radial migration pathways of the left hemisphere was significantly larger than that of the right hemisphere. The volume of posterior radial migration pathways was also larger when compared to the anterior pathways in specimens 22 GW or younger. In contrast, no significant differences were observed in the radial migration pathways of brains older than 22 GW. Moreover, our study did not identify any significant differences in volumetric laterality in the tangential migration pathways. These results suggest that these two neuronal migration pathways develop and regress differently, and radial neuronal migration varies regionally based on hemispheric and anterior -posterior laterality, potentially explaining regional differences in the amount of excitatory neurons that migrate along the radial scaffold. C1 [Miyazaki, Yuta] Chiba Univ, Sch Med, Dept Med, Chiba, Japan. [Song, Jae W.] Yale Univ, Sch Med, Dept Radiol & Biomed Imaging, New Haven, CT USA. [Takahashi, Emi] Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp,Div Newborn Med, Boston, MA USA. [Takahashi, Emi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Takahashi, Emi] Harvard Univ, Sch Med, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston Childrens Hosp, Boston, MA 02115 USA. RP Takahashi, E (reprint author), Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp,Div Newborn Med, Boston, MA USA.; Takahashi, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.; Takahashi, E (reprint author), Harvard Univ, Sch Med, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston Childrens Hosp, Boston, MA 02115 USA. EM emi@nmr.mgh.harvard.edu FU Boston Children's Hospital (BCH); NICHD [R01HD078561, R21HD069001, R03NS091587]; Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health [P41RR14075]; NCRR Shared Instrumentation Grant Program [NIH S10RR023401, S10RR019307, S10RR023043]; High-End Instrumentation Grant Program [NIH S10RR016811]; [NIH MH081896] FX This work was supported by Boston Children's Hospital (BCH), NICHD (R01HD078561, R21HD069001, R03NS091587; ET). This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, NIH P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program (NIH S10RR023401, S10RR019307, and S10RR023043) and High-End Instrumentation Grant Program (NIH S10RR016811). This study was conducted partly using postmortem human brain specimens from the tissue collection at the Department of Neurobiology at Yale University School of Medicine (supported by grant NIH MH081896), which form a part of the BrainSpan Consortium collection (http://www.brainspan.org). The other brain specimens were kindly provided by Dr. Rebecca D. Folkerth, Brigham and Women's Hospital, Boston Children's Hospital and Harvard Medical School. NR 75 TC 0 Z9 0 U1 0 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5129 J9 FRONT NEUROANAT JI Front. Neuroanat. PD JAN 25 PY 2016 VL 10 AR 2 DI 10.3389/fnana.2016.00002 PG 10 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA DB6NX UT WOS:000368632800001 PM 26834572 ER PT J AU Chen, HI Jgamadze, D Serruya, MD Cullen, DK Wolf, JA Smith, DH AF Chen, H. Isaac Jgamadze, Dennis Serruya, Mijail D. Cullen, D. Kacy Wolf, John A. Smith, Douglas H. TI Neural Substrate Expansion for the Restoration of Brain Function SO FRONTIERS IN SYSTEMS NEUROSCIENCE LA English DT Review DE axons; brain repair; neural interfaces; neuronal networks; stem cells; tissue engineering ID PLURIPOTENT STEM-CELLS; LONG-TERM SURVIVAL; CORTICAL-NEURONS; MOTOR CORTEX; IN-VIVO; SUBVENTRICULAR ZONE; AXON REGENERATION; CEREBRAL-CORTEX; ADULT BRAIN; 3D CULTURE AB Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not demonstrated the ability to reestablish the function of large-scale neuronal networks. In this review, we contend that fulfilling the potential of brain substrate expansion will require a significant shift from current methods that emphasize direct manipulations of the brain (e.g., injections of cellular suspensions and the implantation of multi-electrode arrays) to the generation of more sophisticated neural tissues and neural-electric hybrids in vitro that are subsequently transplanted into the brain. Drawing from neural tissue engineering, stem cell biology, and neural interface technologies, this strategy makes greater use of the manifold techniques available in the laboratory to create biocompatible constructs that recapitulate brain architecture and thus are more easily recognized and utilized by brain networks. C1 [Chen, H. Isaac; Jgamadze, Dennis; Cullen, D. Kacy; Wolf, John A.; Smith, Douglas H.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. [Chen, H. Isaac; Cullen, D. Kacy; Wolf, John A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Serruya, Mijail D.] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA. RP Chen, HI (reprint author), Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA.; Chen, HI (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. EM isaac.chen@uphs.upenn.edu FU RRD VA [IK2 RX001479] NR 107 TC 0 Z9 0 U1 6 U2 19 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5137 J9 FRONT SYST NEUROSCI JI Front. Syst. Neurosci. PD JAN 25 PY 2016 VL 10 AR 1 DI 10.3389/fnsys.2016.00001 PG 9 WC Neurosciences SC Neurosciences & Neurology GA DB6HG UT WOS:000368614700001 PM 26834579 ER PT J AU Graf, SA Gopal, AK AF Graf, Solomon A. Gopal, Ajay K. TI Idelalisib for the treatment of non-Hodgkin lymphoma SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE Idelalisib; B-cell; lymphoma; indolent ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MANTLE-CELL LYMPHOMA; FOLLICULAR LYMPHOMA; INDOLENT LYMPHOMA; PHASE-II; PHOSPHATIDYLINOSITOL 3-KINASE-DELTA; PHOSPHOINOSITIDE 3-KINASE; PROTEASOME INHIBITOR; COMBINATION THERAPY; UNTREATED PATIENTS AB IntroductionB-cell Non-Hodgkin lymphomas (B-NHLs) include a number of disease subtypes, each defined by the tempo of disease progression and the identity of the cancerous cell. Idelalisib is a potent, selective inhibitor of the delta isoform of phosphatidylinositol-3-kinase (PI3K), a lipid kinase whose over-activity in B-NHL drives disease progression. Idelalisib has demonstrated activity in indolent B-NHL (iB-NHL) and is approved for use as monotherapy in patients with follicular lymphoma and small lymphocytic lymphoma and in combination with rituximab in patients with chronic lymphocytic leukemia.Areas CoveredHerein we review the development and pharmacology of idelalisib, its safety and efficacy in clinical studies of iB-NHL, and its potential for inclusion in future applications in iB-NHL and in combination with other therapies.Expert OpinionIdelalisib adds to the growing arsenal of iB-NHL pharmacotherapeutics and to the progression of the field toward precision agents with good efficacy and reduced toxicities. Nevertheless, idelalisib carries important risks that require careful patient counseling and monitoring. The appropriate sequencing of idelalisib with other proven treatment options in addition to its potential for combination with established or novel drugs will be borne out in ongoing and planned investigations. C1 [Graf, Solomon A.; Gopal, Ajay K.] Univ Washington, Dept Med, Seattle, WA USA. [Graf, Solomon A.; Gopal, Ajay K.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Graf, Solomon A.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Gopal, AK (reprint author), Univ Washington, Med, 825 Eastlake Ave E, Seattle, WA USA. EM agopal@u.washington.edu FU NCI [P01CA44991, K24CA184039]; Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Cancer Center [P30 CA015704]; NIH [5T32HL007093]; Seattle Genetics Inc; Gilead Sciences; Janssen Pharmaceuticals; Spectrum Pharmaceuticals FX This work was supported by research funding from NCI P01CA44991, K24CA184039, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Cancer Center Support Grant P30 CA015704, and gifts from Frank and Betty Vandermeer, Don and Debbie Hunkins, and the Mary Aileen Wright Memorial Fund. S.A.G. received support from NIH 5T32HL007093. A Gopal has received consulting fees from Seattle Genetics Inc, Gilead Sciences, Janssen Pharmaceuticals and Spectrum Pharmaceuticals within the last 12 months. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed NR 69 TC 5 Z9 5 U1 1 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD JAN 22 PY 2016 VL 17 IS 2 BP 265 EP 274 DI 10.1517/14656566.2016.1135130 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DD8HT UT WOS:000370167700001 PM 26818003 ER PT J AU Mananga, ES Charpentier, T AF Mananga, Eugene Stephane Charpentier, Thibault TI On the Floquet-Magnus expansion: Applications in solid-state nuclear magnetic resonance and physics SO PHYSICS REPORTS-REVIEW SECTION OF PHYSICS LETTERS LA English DT Review ID ANGLE-SPINNING NMR; RADIOFREQUENCY PULSE SEQUENCES; DEPENDENT SCHRODINGER-EQUATION; AVERAGE HAMILTONIAN THEORY; QUANTUM-FIELD THEORY; LIOUVILLE SUPERMATRIX APPROACH; LINEAR-DIFFERENTIAL EQUATIONS; UNIFORMLY LABELED MOLECULE; ANISOTROPY CORRELATION NMR; CHEMICAL-SHIFT ANISOTROPY AB Theoretical approaches are useful and powerful tools for more accurate and efficient spin dynamics simulation to understand experiments and devising new RF pulse sequence in nuclear magnetic resonance. Solid-state NMR is definitely a timely topic or area of research, and not many papers on the respective theories are available in the literature of nuclear magnetic resonance or physics reports. This report presents the power and the salient features of the promising theoretical approach called Floquet-Magnus expansion that is helpful to describe the time evolution of the spin system at all times in nuclear magnetic resonance. The report presents a broad view of algorithms of spin dynamics, based on promising and useful theory of Floquet-Magnus expansion. This theory provides procedures to control and describe the spin dynamics in solid-state NMR. Major applications of the Floquet-Magnus expansion are illustrated by simple solid-state NMR and physical applications such as in nuclear, atomic, molecular physics, and quantum mechanics, NMR, quantum field theory and high energy physics, electromagnetism, optics, general relativity, search of periodic orbits, and geometric control of mechanical systems. The aim of this report is to bring to the attention of the spin dynamics community, the bridge that exists between solid-state NMR and other related fields of physics and applied mathematics. This review article also discusses future potential theoretical directions in solid-state NMR. (C) 2015 Elsevier B.V. All rights reserved. C1 [Mananga, Eugene Stephane] Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. [Mananga, Eugene Stephane] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging Phys, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. [Charpentier, Thibault] CEA, IRAMIS, CNRS UMR 3299, Serv Interdisciplinaire Syst Mol & Mat, F-91191 Gif Sur Yvette, France. RP Mananga, ES (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA.; Mananga, ES (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging Phys, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM emananga@gradcenter.cuny.edu; thibault.charpentier@cea.fr RI Charpentier, Thibault/A-3557-2010 OI Charpentier, Thibault/0000-0002-3034-1389 FU National Institute of Health (NIH) of USA [R01-HL110241, T32 EB013180] FX Eugene S. Mananga acknowledges assistance from Harvard University, Harvard Medical School (HMS), Massachusetts General Hospital (MGH), and the National Institute of Health (NIH) of USA, under Grants R01-HL110241 and T32 EB013180. The author particularly thanks the Division of Nuclear Medicine and the Department of Radiology for allowing him to work partially on this NMR and Physics Report during his NIHT32 tenure time at Harvard and Massachusetts General Hospital. The authors are grateful for encouragement and fruitful discussions with Professor Dr. Eduard B. Fel'dman (Academy of Sciences of the Soviet Union, USSR) for reading the manuscript and providing very useful advises particularly in the context of Provotorov's theory. The first author recognizes that the idea of writing a general review on various theories used to control the spin dynamics in the field of nuclear magnetic resonance came to his mind for the first time while he was a Postdoctorate Research Associate at the National High Magnetic Field Laboratory of USA, working on the application of Solid-State Nuclear Magnetic Resonance to Structural Biology and Membrane Proteins. He was first, introduced to solid-state nuclear magnetic resonance by Prof. Steven Greenbaum (City University of New York-Hunter College) during his graduate work on "High Pressure NMR" [210,211]. During and after his graduate studies, the first author has benefited from enlightening discussions, mentorship, and strong support from Prof. Joel Gersten (City College of New York). Special thanks for that, as much as for the kind of hospitality extended to him during his graduate studies at City College of the City University of New York. The first author is also grateful to Emeritus University Distinguished Professor of Physics, Herman Z. Cummins (City College of New York), for giving him advanced tutoring on modern physics topics during the preparation of the "hard Physics" qualifying exam of the Graduate Center. He had his first interest to the technique of average Hamiltonian theory (AHT) while working with Dr. Gregory Boutis (City University of New York, Brooklyn College). The first author also gives special thanks to Dr. Thibault Charpentier (French Atomic Energy Commission, CEA-Saclay) for introducing him to the field of Floquet theory during his work at CEA-Saclay. We thank collaboratoration with Prof. Bingwen Hu (Shanghai Key Laboratory of Magnetic Resonance at East China Normal University) and his helpful discussions. Advices and intellectual support from Prof. Dennis Brown, Prof. Frederic Fahey, and Prof. Arkadiusz Sitek (Harvard University, Massachusetts General Hospital, and Boston Children Hospital) are acknowledged. Physics teaching support from Prof. Lorcan Folan and Prof. Valery Sheverev (New York University) is also acknowledged. Friendly discussions with Drs. Christopher Renner, Michele Vittadello, and George Bennett (City University of New York, HC, MEC, BCC) are appreciated. The author also thanks Dr. Gael De Paepe (French Atomic Energy Commission, CEA-Grenoble) for providing him his preprint article on TSAR. Finally, the author thanks fruitful and illuminating lectures (Edward Witten, Philip Anderson, etc.) on condensed matter theory during the 2015 summer school (Princeton University and the Institute of Advanced Studies). The contents of this paper are solely the responsibility of the author and do not represent the official views of NIH/HMS/MGH. NR 260 TC 3 Z9 3 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0370-1573 EI 1873-6270 J9 PHYS REP JI Phys. Rep.-Rev. Sec. Phys. Lett. PD JAN 22 PY 2016 VL 609 BP 1 EP 49 DI 10.1016/j.physrep.2015.10.005 PG 49 WC Physics, Multidisciplinary SC Physics GA DC4RY UT WOS:000369209200001 ER PT J AU Roh, J Rhee, J Chaudhari, V Rosenzweig, A AF Roh, Jason Rhee, James Chaudhari, Vinita Rosenzweig, Anthony TI The Role of Exercise in Cardiac Aging From Physiology to Molecular Mechanisms SO CIRCULATION RESEARCH LA English DT Review DE aging; cardiovascular diseases; exercise; heart; phenotype ID PRESERVED EJECTION FRACTION; CHRONIC HEART-FAILURE; GROWTH-FACTOR-I; MITOCHONDRIAL-DNA MUTATIONS; LEFT-VENTRICULAR COMPLIANCE; OXIDATIVE STRESS-RESPONSE; ADENOVIRAL GENE-TRANSFER; AGE-ASSOCIATED CHANGES; HUMAN SKELETAL-MUSCLE; TRAINED OLD RATS AB Aging induces structural and functional changes in the heart that are associated with increased risk of cardiovascular disease and impaired functional capacity in the elderly. Exercise is a diagnostic and therapeutic tool, with the potential to provide insights into clinical diagnosis and prognosis, as well as the molecular mechanisms by which aging influences cardiac physiology and function. In this review, we first provide an overview of how aging impacts the cardiac response to exercise, and the implications this has for functional capacity in older adults. We then review the underlying molecular mechanisms by which cardiac aging contributes to exercise intolerance, and conversely how exercise training can potentially modulate aging phenotypes in the heart. Finally, we highlight the potential use of these exercise models to complement models of disease in efforts to uncover new therapeutic targets to prevent or treat heart disease in the aging population. C1 [Roh, Jason; Rhee, James; Chaudhari, Vinita; Rosenzweig, Anthony] Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA. [Roh, Jason] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Rhee, James] Harvard Univ, Sch Med, Boston, MA USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Bigelow 800,Mailstop 817, Boston, MA 02114 USA. EM arosenzweig@partners.org FU National Institutes of Health [R01HL110733, R01HL122987, T32HL073734, T32GM007592]; LaDue Fellowship Award from Harvard Medical School FX This work was supported by grants from the National Institutes of Health (A. Rosenzweig [R01HL110733 and R01HL122987], Dr Roh [T32HL073734], and J. Rhee [T32GM007592]). Roh was also supported by a LaDue Fellowship Award from Harvard Medical School. A. Rosenzweig is a principal faculty member of the Harvard Stem Cell Institute. NR 220 TC 3 Z9 3 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD JAN 22 PY 2016 VL 118 IS 2 BP 279 EP 295 DI 10.1161/CIRCRESAHA.115.305250 PG 17 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA DB7WZ UT WOS:000368729100014 PM 26838314 ER PT J AU Sinha, P Aarnisalo, P Chubb, R Poulton, IJ Guo, J Nachtrab, G Kimura, T Swami, S Saeed, H Chen, M Weinstein, LS Schipani, E Sims, NA Kronenberg, HM Wu, JY AF Sinha, Partha Aarnisalo, Piia Chubb, Rhiannon Poulton, Ingrid J. Guo, Jun Nachtrab, Gregory Kimura, Takaharu Swami, Srilatha Saeed, Hamid Chen, Min Weinstein, Lee S. Schipani, Ernestina Sims, Natalie A. Kronenberg, Henry M. Wu, Joy Y. TI Loss of G(s)alpha in the Postnatal Skeleton Leads to Low Bone Mass and a Blunted Response to Anabolic Parathyroid Hormone Therapy SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OSTEOBLASTIC CELLS; MESENCHYMAL PROGENITORS; POSTMENOPAUSAL WOMEN; INTERMITTENT PTH; PHOSPHOLIPASE-C; MINERAL DENSITY; PROTEIN-KINASE; IN-VIVO; DIFFERENTIATION; RECEPTOR AB Parathyroid hormone (PTH) is an important regulator of osteoblast function and is the only anabolic therapy currently approved for treatment of osteoporosis. The PTH receptor (PTH1R) is a G protein-coupled receptor that signals via multiple G proteins including G(s)alpha. Mice expressing a constitutively active mutant PTH1R exhibited a dramatic increase in trabecular bone that was dependent upon expression of G(s)alpha in the osteoblast lineage. Postnatal removal of G(s)alpha in the osteoblast lineage (P-G(s)alpha(OsxKO) mice) yielded markedly reduced trabecular and cortical bone mass. Treatment with anabolic PTH(1-34) (80 mu g/kg/day) for 4 weeks failed to increase trabecular bone volume or cortical thickness in male and female P-G(s)alpha(OsxKO) mice. Surprisingly, in both male and female mice, PTH administration significantly increased osteoblast numbers and bone formation rate in both control and P-G(s)alpha(OsxKO) mice. In mice that express a mutated PTH1R that activates adenylyl cyclase and protein kinase A (PKA) via G(s)alpha but not phospholipase C via G(q/11) (D/D mice), PTH significantly enhanced bone formation, indicating that phospholipase C activation is not required for increased bone turnover in response to PTH. Therefore, although the anabolic effect of intermittent PTH treatment on trabecular bone volume is blunted by deletion of G(s)alpha in osteoblasts, PTH can stimulate osteoblast differentiation and bone formation. Together these findings suggest that alternative signaling pathways beyond G(s)alpha and G(q/11) act downstream of PTH on osteoblast differentiation. C1 [Sinha, Partha; Aarnisalo, Piia; Chubb, Rhiannon; Guo, Jun; Nachtrab, Gregory; Kronenberg, Henry M.; Wu, Joy Y.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Aarnisalo, Piia] Univ Helsinki, Dept Clin Chem, Helsinki 00029, Finland. [Aarnisalo, Piia] Univ Helsinki, Cent Hosp, HUSLAB, Lab Serv, Helsinki 00029, Finland. [Poulton, Ingrid J.; Sims, Natalie A.] Univ Melbourne, St Vincents Inst, Fitzroy, Vic 3065, Australia. [Poulton, Ingrid J.; Sims, Natalie A.] Univ Melbourne, St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia. [Kimura, Takaharu; Swami, Srilatha; Saeed, Hamid; Wu, Joy Y.] Stanford Univ, Sch Med, Div Endocrinol, 300 Pasteur Dr,S-025, Stanford, CA 94305 USA. [Chen, Min; Weinstein, Lee S.] NIDDK, NIH, Metab Dis Branch, Bethesda, MD 20892 USA. [Schipani, Ernestina] Univ Michigan, Dept Orthoped Surg, Ann Arbor, MI 48109 USA. [Schipani, Ernestina] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. RP Wu, JY (reprint author), Stanford Univ, Sch Med, Div Endocrinol, 300 Pasteur Dr,S-025, Stanford, CA 94305 USA. EM jywu1@stanford.edu FU National Institutes of Health [AR054741, AR059942, AR061228, DK011794]; NIDDK Intramural Research Program FX This work was supported by National Institutes of Health Grants AR054741 and AR059942 (to J. Y. W.), AR061228 (to P. S.), and DK011794 (to H. M. K.) and the NIDDK Intramural Research Program (to M. C. and L. S. W.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 50 TC 4 Z9 4 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 22 PY 2016 VL 291 IS 4 BP 1631 EP 1642 DI 10.1074/jbc.M115.679753 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DB6JI UT WOS:000368620700008 PM 26598522 ER PT J AU Novgorodov, SA Riley, CL Keffler, JA Yu, J Kindy, MS Macklin, WB Lombard, DB Gudz, TI AF Novgorodov, Sergei A. Riley, Christopher L. Keffler, Jarryd A. Yu, Jin Kindy, Mark S. Macklin, Wendy B. Lombard, David B. Gudz, Tatyana I. TI SIRT3 Deacetylates Ceramide Synthases IMPLICATIONS FOR MITOCHONDRIAL DYSFUNCTION AND BRAIN INJURY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; MANGANESE SUPEROXIDE-DISMUTASE; PERMEABILITY TRANSITION PORE; RADIATION-INDUCED APOPTOSIS; OXYGEN SPECIES GENERATION; REACTIVE OXYGEN; CYCLOPHILIN-D; CELL-DEATH; SERINE PALMITOYLTRANSFERASE; SPHINGOLIPID BIOSYNTHESIS AB Experimental evidence supports the role of mitochondrial ceramide accumulation as a cause of mitochondrial dysfunction and brain injury after stroke. Herein, we report that SIRT3 regulates mitochondrial ceramide biosynthesis via deacetylation of ceramide synthase (CerS) 1, 2, and 6. Reciprocal immunoprecipitation experiments revealed that CerS1, CerS2, and CerS6, but not CerS4, are associated with SIRT3 in cerebral mitochondria. Furthermore, CerS1, -2, and -6 are hyperacetylated in the mitochondria of SIRT3-null mice, and SIRT3 directly deacetylates the ceramide synthases in aNAD(+)-dependent manner that increases enzyme activity. Investigation of the SIRT3 role in mitochondrial response to brain ischemia/reperfusion (IR) showed that SIRT3-mediated deacetylation of ceramide synthases increased enzyme activity and ceramide accumulation after IR. Functional studies demonstrated that absence of SIRT3 rescued the IR-induced blockade of the electron transport chain at the level of complex III, attenuated mitochondrial outer membrane permeabilization, and decreased reactive oxygen species generation and protein carbonyls in mitochondria. Importantly, Sirt3 gene ablation reduced the brain injury after IR. These data support the hypothesis that IR triggers SIRT3-dependent deacetylation of ceramide synthases and the elevation of ceramide, which could inhibit complex III, leading to increased reactive oxygen species generation and brain injury. The results of these studies highlight a novel mechanism of SIRT3 involvement in modulating mitochondrial ceramide biosynthesis and suggest an important role of SIRT3 in mitochondrial dysfunction and brain injury after experimental stroke. C1 [Riley, Christopher L.; Kindy, Mark S.; Gudz, Tatyana I.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Novgorodov, Sergei A.; Keffler, Jarryd A.; Yu, Jin; Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci Med, Charleston, SC 29425 USA. [Macklin, Wendy B.] Univ Colorado, Dept Cell & Dev Biol, Aurora, CO 80045 USA. [Lombard, David B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Lombard, David B.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. RP Gudz, TI (reprint author), 114 Doughty St, Charleston, SC 29425 USA. EM gudz@musc.edu FU National Institutes of Health [R01NS083544, R01GM101171, P30 GM103339]; Veterans Affairs Merit Award [I01BX001104] FX This work was supported in part by National Institutes of Health Grants R01NS083544 (to T. I. G.), R01GM101171 (to D. B. L.), and P30 GM103339 (to Lipidomics Core Facility. Medical University of South Carolina) and Veterans Affairs Merit Award I01BX001104 (to T. I. G.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 81 TC 4 Z9 4 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 22 PY 2016 VL 291 IS 4 BP 1957 EP 1973 DI 10.1074/jbc.M115.668228 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DB6JI UT WOS:000368620700033 PM 26620563 ER PT J AU Belstrom, D Holmstrup, P Bardow, A Kokaras, A Fiehn, NE Paster, BJ AF Belstrom, Daniel Holmstrup, Palle Bardow, Allan Kokaras, Alexis Fiehn, Nils-Erik Paster, Bruce J. TI Temporal Stability of the Salivary Microbiota in Oral Health SO PLOS ONE LA English DT Article ID PERIODONTAL-DISEASE; BIOMARKERS; INDIVIDUALS; PATTERNS; DIAGNOSTICS; DIVERSITY; ANALYTES; LESIONS; COHORT; ADULTS AB Objectives Saliva is a biological fluid suitable for biomarker analysis, and differences in the salivary microbiota in oral health and disease have been reported. For such comparative analyses, time of sampling is critical since the bacterial composition may vary throughout the day, i.e., diurnal variation. The purpose of this study is to compare the salivary microbiome over time to determine the optimal time for sampling. Design Stimulated saliva samples were collected from 5 orally healthy individuals in 4 h intervals for 24 h, and collection was repeated 7 days later (number of samples per person, n = 12, total number of samples, n = 60). Salivary microbiota was analyzed using the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS), and statistical analysis was performed using the Kruskal-Wallis test with Benjamini-Hochberg's correction for multiple comparisons, cluster analysis, principal component analysis and correspondence analysis. Results From a total of 60 saliva samples, 477 probe targets were collectively identified with a mean number of probes per sample of 207 (range: 153-307). Little or no variation in microbial profiles within subjects was observed over time. Conclusions Although there was considerable variation between subjects, microbial profiles within subjects were stable throughout a 24 hour period and after 1 week. Since there is little or no evidence of diurnal variation of the salivary microbiome, time of sampling of saliva is not critical for perturbation or other microbial studies. C1 [Belstrom, Daniel; Holmstrup, Palle] Univ Copenhagen, Sect Periodontol Microbiol & Community Dent, Fac Hlth & Med Sci, Sch Dent, Copenhagen, Denmark. [Bardow, Allan] Univ Copenhagen, Sch Dent, Dept Oral Med, Copenhagen, Denmark. [Kokaras, Alexis; Paster, Bruce J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Fiehn, Nils-Erik] Univ Copenhagen, Dept Immunol & Microbiol, Copenhagen, Denmark. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. RP Belstrom, D (reprint author), Univ Copenhagen, Sect Periodontol Microbiol & Community Dent, Fac Hlth & Med Sci, Sch Dent, Copenhagen, Denmark. EM dbel@sund.ku.dk FU Danish Dental Association; Danish Foundation of Mutual Efforts in Dental Care; Trygfonden; Simon Spies Foundation; NIH [DE021565] FX This study was supported by external financial support by: the Danish Dental Association, the Danish Foundation of Mutual Efforts in Dental Care, Trygfonden, and the Simon Spies Foundation. It was also funded in part from NIH grant DE021565 (BJP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript NR 35 TC 5 Z9 5 U1 3 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 22 PY 2016 VL 11 IS 1 AR e0147472 DI 10.1371/journal.pone.0147472 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB6WB UT WOS:000368655300111 PM 26799067 ER PT J AU Cahill, CM Zhu, WS Oziolor, E Yang, YJ Tam, B Rajanala, S Rogers, JT Walker, WA AF Cahill, Catherine M. Zhu, Weishu Oziolor, Elias Yang, Yao-Jong Tam, Bosco Rajanala, Susruthi Rogers, Jack T. Walker, W. Allan TI Differential Expression of the Activator Protein 1 Transcription Factor Regulates Interleukin-1 beta Induction of Interleukin 6 in the Developing Enterocyte SO PLOS ONE LA English DT Article ID DEVELOPING HUMAN INTESTINE; EPITHELIAL-CELL LINE; C-JUN; NECROTIZING ENTEROCOLITIS; SIGNAL-TRANSDUCTION; AP-1; IL-6; PATHWAY; INJURY; INFLAMMATION AB The innate immune response is characterized by activation of transcription factors, nuclear factor kappa B and activator protein-1 and their downstream targets, the pro-inflammatory cytokines including interleukin 1 beta and interleukin 6. Normal development of this response in the intestine is critical to survival of the human neonate and delays can cause the onset of devastating inflammatory diseases such as necrotizing enterocolitis. Previous studies have addressed the role of nuclear factor kappa B in the development of the innate immune response in the enterocyte, however despite its central role in the control of multiple pro-inflammatory cytokine genes, little is known on the role of Activator Protein 1 in this response in the enterocyte. Here we show that the canonical Activator Protein 1 members, cJun and cFos and their upstream kinases JNK and p38 play an essential role in the regulation of interleukin 6 in the immature enterocyte. Our data supports a model whereby the cFos/cJun heterodimer and the more potent cJun homodimer downstream of JNK are replaced by less efficient JunD containing dimers, contributing to the decreased responsiveness to interleukin 1 beta and decreased interleukin 6 secretion observed in the mature enterocyte. The tissue specific expression of JunB in colonocytes and colon derived tissues together with its ability to repress Interleukin-1 beta induction of an Interleukin-6 gene reporter in the NCM-460 colonocyte suggests that induction of JunB containing dimers may offer an attractive therapeutic strategy for the control of IL-6 secretion during inflammatory episodes in this area of the intestine C1 [Cahill, Catherine M.; Tam, Bosco; Rajanala, Susruthi; Rogers, Jack T.] Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Charlestown, MA USA. [Cahill, Catherine M.; Zhu, Weishu; Tam, Bosco; Rajanala, Susruthi; Rogers, Jack T.; Walker, W. Allan] Harvard Univ, Sch Med, Charlestown, MA USA. [Zhu, Weishu; Walker, W. Allan] Massachusetts Gen Hosp Children, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Charlestown, MA USA. [Oziolor, Elias] Baylor Univ, Dept Environm Sci, One Bear Pl 97266, Waco, TX 76798 USA. [Yang, Yao-Jong] Natl Cheng Kung Univ, Dept Pediat, Tainan 701, Taiwan. [Yang, Yao-Jong] Natl Cheng Kung Univ, Dept Internal Med, Tainan 701, Taiwan. RP Cahill, CM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Charlestown, MA USA. EM ccahill@helix.mgh.harvard.edu RI Oziolor, Elias/P-6961-2016 OI Oziolor, Elias/0000-0002-4078-1054 FU National Institute of Child Health and Human Development [R01HD012437Supplement29, R01HD012437]; National Institute of Neurological Disorders and Stroke [NS077079-01A1] FX External Funding was obtained as follows: CMC R01HD012437Supplement29 (National Institute of Child Health and Human Development, https://www.nichd.nih.gov/Pages/index.aspx), WAW R01HD012437 (National Institute of Child Health and Human Development, https://www.nichd.nih.gov/Pages/index.aspx), JTR NS077079-01A1 (National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/). 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 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 22 PY 2016 VL 11 IS 1 AR e0145184 DI 10.1371/journal.pone.0145184 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB6WB UT WOS:000368655300003 PM 26799482 ER PT J AU Toro, ML Eke, C Pearlman, J AF Toro, Maria L. Eke, Chika Pearlman, Jonathan TI The impact of the World Health Organization 8-steps in wheelchair service provision in wheelchair users in a less resourced setting: a cohort study in Indonesia SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Wheelchairs; Wheelchair service provision; Quality of life; Participation; Wheelchair skills; Less resourced settings ID SPINAL-CORD-INJURY; ASSISTIVE TECHNOLOGY USE; LOW-COST WHEELCHAIR; QUALITY-OF-LIFE; DEVELOPING-COUNTRIES; ADVERSE CONSEQUENCES; SKILLS; REHABILITATION; DISABILITIES; CONVENTION AB Background: For people who have a mobility impairment, access to an appropriate wheelchair is an important step towards social inclusion and participation. The World Health Organization Guidelines for the Provision of Manual Wheelchairs in Less Resourced Settings emphasize the eight critical steps for appropriate wheelchair services, which include: referral, assessment, prescription, funding and ordering, product preparation, fitting and adjusting, user training, and follow-up and maintenance/repairs. The purpose of this study was to investigate how the provision of wheelchairs according to the World Health Organization's service provision process by United Cerebral Palsy Wheels for Humanity in Indonesia affects wheelchair recipients compared to wait-listed controls. Methods: This study used a convenience sample (N = 344) of Children, Children with proxies, Adults, and Adults with proxies who were on a waiting list to receive a wheelchair as well as those who received one. Interviews were conducted at baseline and a 6 month follow-up to collect the following data: Demographics and wheelchair use questions, the World Health Organization Quality of Life-BREF, Functional Mobility Assessment, Craig Handicap Assessment Recording Technique Short Form. The Wheelchair Assessment Checklist and Wheelchair Skills Test Questionnaire were administered at follow up only. Results: 167 participants were on the waiting list and 142 received a wheelchair. Physical health domain in the World Health Organization Quality of Life-BREF improved significantly for women who received a wheelchair (p = 0.044) and environmental health improved significantly for women and men who received a wheelchair as compared to those on the waiting list (p < 0.017). Satisfaction with the mobility device improved significantly for Adults with proxies and Children with proxies as compared to the waiting list (p < 0.022). Only 11 % of Adults who received a wheelchair reported being able to perform a "wheelie". The condition of Roughrider wheelchairs was significantly better than the condition of kids wheelchairs for Children with proxies as measured by the Wheelchair Assessment Checklist (p = 0.019). Conclusions: Wheelchair provision according to World Health Organization's 8-Steps in a less-resourced setting has a range of positive outcomes including increased satisfaction with the mobility device and better quality of life. Wheelchair provision service could be improved by providing more hours of wheelchair skills training. There is a need for outcome measures that are validated across cultures and languages. C1 [Toro, Maria L.; Pearlman, Jonathan] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Toro, Maria L.; Pearlman, Jonathan] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Toro, Maria L.] Escuela Ingn Antioquia, Programa Ingn Biomed, Envigado, Antioquia, Colombia. [Toro, Maria L.] Univ CES, Envigado, Antioquia, Colombia. [Eke, Chika] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Pearlman, J (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA.; Pearlman, J (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. EM Jlp46@pitt.edu FU United States Agency for International Development grant [GPO-A-00-04-00021-00 SPANS 001]; National Science Foundation; ASPIRE Grant [1262670]; VA Center Grant [B6789C] FX Funding provided by United States Agency for International Development grant to World Learning GPO-A-00-04-00021-00 SPANS 001, the National Science Foundation, ASPIRE Grant #1262670 and VA Center Grant #B6789C. The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. The authors would like to thank the personnel of UCP Wheels for Humanity and UCP Roda Untuk Kemanusiaan specially Heny Prabaningrum. The authors will like to thank Dr. Andi Saptono for his contribution during the on-site training week in Indonesia. NR 72 TC 1 Z9 1 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD JAN 22 PY 2016 VL 16 AR 26 DI 10.1186/s12913-016-1268-y PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DB5SL UT WOS:000368573800001 PM 26801984 ER PT J AU Nossenson, N Magal, A Messer, H AF Nossenson, Nir Magal, An Messer, Hagit TI Detection of stimuli from multi-neuron activity: Empirical study and theoretical implications SO NEUROCOMPUTING LA English DT Article DE Stimulus detection; Gaussian signal in Gaussian noise; Electrophysiology; Multi unit activity; Decision making; Glutamate uptake rate ID AUDITORY-NERVE FIBERS; ENERGY DETECTION; GLUTAMATE UPTAKE; DECISION-MAKING; NORMAL WAKEFULNESS; RESPONSE PATTERNS; ASTROCYTES; CALCIUM; SIGNALS; MODELS AB We report on detection results obtained in 20 experiments in which the presence of an external auditory stimulus had to be detected from observing electrophysiological multi-unit activity in the brain stem of rats. The performance of the optimal Gaussian-signal-in-Gaussian-noise (model-based) detector is compared to that of the energy detector which is widely used in electrophysiology as well as in many other disciplines with similar signal characteristics. It is shown that the optimal model based detector is indeed superior, but the performance gap in favor of the optimal detector is substantial mainly in very low probabilities of false alarm errors. The performance of the energy detector is close to optimum in moderate and high probabilities of false alarm error. Furthermore, the energy detector is shown to be more resilient to isolated and short, yet intense disturbances. We discuss a conjecture inspired by the model underlying the optimal detector and the empirical results, that the neural tissue itself executes a modified energy detection scheme, and we review experimental results from the literature that allegedly support this conjecture. (C) 2015 Elsevier B.V. All rights reserved. C1 [Nossenson, Nir] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Nossenson, Nir] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Magal, An] Tel Aviv Univ, Sch Psychol Sci, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel. [Messer, Hagit] Tel Aviv Univ, Sch Elect Engn, IL-69978 Tel Aviv, Israel. RP Nossenson, N (reprint author), Massachusetts Gen Hosp, Dept Neurol, 50 Blossom St, Boston, MA 02114 USA. EM nnossenson@mgh.harvard.edu; poochoor@gmail.com; messer@eng.tau.ac.il NR 65 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-2312 EI 1872-8286 J9 NEUROCOMPUTING JI Neurocomputing PD JAN 22 PY 2016 VL 174 BP 822 EP 837 DI 10.1016/j.neucom.2015.10.007 PN B PG 16 WC Computer Science, Artificial Intelligence SC Computer Science GA CZ7JY UT WOS:000367276900027 ER PT J AU Tabebordbar, M Zhu, KX Cheng, JKW Chew, WL Widrick, JJ Yan, WX Maesner, C Wu, EY Xiao, R Ran, FA Cong, L Zhang, F Vandenberghe, LH Church, GM Wagers, AJ AF Tabebordbar, Mohammadsharif Zhu, Kexian Cheng, Jason K. W. Chew, Wei Leong Widrick, Jeffrey J. Yan, Winston X. Maesner, Claire Wu, Elizabeth Y. Xiao, Ru Ran, F. Ann Cong, Le Zhang, Feng Vandenberghe, Luk H. Church, George M. Wagers, Amy J. TI In vivo gene editing in dystrophic mouse muscle and muscle stem cells SO SCIENCE LA English DT Article ID MUSCULAR-DYSTROPHY; EXONS 45-55; DMD GENE; MICE; DNA; MUTATION; SYSTEM; CAS9 AB Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the mutated transcript can produce an in-frame mRNA and a truncated, but still functional, protein. In this study, we developed and tested a direct gene-editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored the Dmd reading frame in myofibers, cardiomyocytes, and muscle stem cells after local or systemic delivery. AAV-Dmd CRISPR treatment partially recovered muscle functional deficiencies and generated a pool of endogenously corrected myogenic precursors in mdx mouse muscle. C1 [Tabebordbar, Mohammadsharif; Zhu, Kexian; Cheng, Jason K. W.; Maesner, Claire; Wu, Elizabeth Y.; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Tabebordbar, Mohammadsharif; Zhu, Kexian; Cheng, Jason K. W.; Maesner, Claire; Wu, Elizabeth Y.; Wagers, Amy J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Tabebordbar, Mohammadsharif; Chew, Wei Leong] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA 02115 USA. [Zhu, Kexian] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Chew, Wei Leong; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Widrick, Jeffrey J.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Genet & Program Genom, Boston, MA 02115 USA. [Yan, Winston X.; Ran, F. Ann; Cong, Le; Zhang, Feng] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Yan, Winston X.; Ran, F. Ann; Cong, Le; Zhang, Feng] MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Yan, Winston X.; Ran, F. Ann; Cong, Le; Zhang, Feng] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Xiao, Ru; Vandenberghe, Luk H.] Sr,hepens Eye Res Inst, Grousbeck Gene Therapy Ctr, Boston, MA 02114 USA. [Xiao, Ru; Vandenberghe, Luk H.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Wagers, AJ (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM amy_wagers@harvard.edu OI Zhu, Kexian/0000-0002-2321-5085 FU Howard Hughes Medical Institute; NIH [1DP2OD004345, 5U01HL100402, 5PN2EY018244]; National Institute of General Medical Sciences (NIGMS), NIH [T2GM007753]; National Institute of Mental Health, NIH [5DP1-MH100706]; National Institute of Diabetes and Digestive and Kidney Diseases, NIH [5R01DK097768-03]; Waterman Award from the NSF; Keck Foundation; New York Stem Cell Foundation; Damon Runyon Foundation; Searle Scholars Foundation; Merkin Foundation; Vallee Foundation; B. Metcalfe; National Science Scholarship from the Agency for Science, Technology, and Research (A*STAR), Singapore; National Human Genome Research Institute (NIGMS), NIH, Centers of Excellence in Genomic Science [P50 HG005550]; Regeneron Pharmaceuticals; Cowen; Jefferies; Sectoral FX We thank the Harvard Department of Stem Cell and Regenerative Biology-Harvard Stem Cell Institute Flow Cytometry Core, the Schepens Eye Research Institute-Massachusetts Eye and Ear Institute Gene Transfer Vector Core, the Parker lab at Harvard and J. Goldstein for technical assistance. Work was funded in part by grants from Howard Hughes Medical Institute and NIH (1DP2OD004345, 5U01HL100402, and 5PN2EY018244) to A.J.W. M.T. is an Albert J. Ryan fellow. F.A.R. is a Junior Fellow at the Harvard Society of Fellows. W.X.Y. was supported by T2GM007753 from the National Institute of General Medical Sciences (NIGMS), NIH. F.Z. is a New York Stem Cell Foundation Robertson Investigator and is supported by National Institute of Mental Health, NIH (5DP1-MH100706) and National Institute of Diabetes and Digestive and Kidney Diseases, NIH (5R01DK097768-03); a Waterman Award from the NSF; the Keck, New York Stem Cell, Damon Runyon, Searle Scholars, Merkin, and Vallee Foundations; and B. Metcalfe. W.L.C. is supported by the National Science Scholarship from the Agency for Science, Technology, and Research (A*STAR), Singapore. G.M.C. is supported for this work by National Human Genome Research Institute (NIGMS), NIH, Centers of Excellence in Genomic Science, P50 HG005550. Content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or NIH. M.T., A.J.W., W.L.C., and G.M.C. are inventors on a patent application (PCT/US15/63181) filed by Harvard University related to in vivo genetic modifications and gene editing in muscle. G.M.C. is an inventor on issued patents (US9023649 and US9074199) filed by Harvard University related to CRISPR. L.H.V. is an inventor on a patent application (US2007036760) filed by the University of Pennsylvania related to AAV capsid sequences. F.Z., L.C., F.A.R., and W.Y. are inventors on patents and patent applications (8,865,406; 8,906,616; and accepted EP 2898075, from international patent application WO 2014/093635) filed by the Broad Institute related to SaCas9-optimized components and systems. A.J.W. is an advisor for Fate Therapeutics. G.M.C and F.Z. are founders and scientific advisors of Editas Medicine, and F.Z. is a scientific advisor for Horizon Discovery. G.M.C. has equity in Caribou/Intellia, Egenesis, and Editas (for full disclosure list, see: http://arep.med.harvard.edu/gmc/tech.html). L.H.V. is cofounder, shareholder, member of the scientific advisory board, and consultant for GenSight Biologics, a consultant to Novartis and Eleven Bio, and has received honoraria and consulting fees from Regeneron Pharmaceuticals and Cowen, Jefferies, and Sectoral. AAV9 vector sequences are available through a material transfer agreement (MTA) from the University of Pennsylvania. SaCas9 plasmids are openly available through a Uniform Biological MTA from Addgene. NR 26 TC 109 Z9 112 U1 38 U2 106 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 22 PY 2016 VL 351 IS 6271 BP 407 EP 411 DI 10.1126/science.aad5177 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB3VH UT WOS:000368440500046 PM 26721686 ER PT J AU Benarroch-Popivker, D Pisano, S Mendez-Bermudez, A Lototska, L Kaur, P Bauwens, S Djerbi, N Latrick, CM Fraisier, V Pei, B Gay, A Jaune, E Foucher, K Cherfils-Vicini, J Aeby, E Miron, S Londono-Vallejo, A Ye, J Le Du, MH Wang, H Gilson, E Giraud-Panis, MJ AF Benarroch-Popivker, Delphine Pisano, Sabrina Mendez-Bermudez, Aaron Lototska, Liudmyla Kaur, Parminder Bauwens, Serge Djerbi, Nadir Latrick, Chrysa M. Fraisier, Vincent Pei, Bei Gay, Alexandre Jaune, Emilie Foucher, Kevin Cherfils-Vicini, Julien Aeby, Eric Miron, Simona Londono-Vallejo, Arturo Ye, Jing Le Du, Marie-Helene Wang, Hong Gilson, Eric Giraud-Panis, Marie-Josephe TI TRF2-Mediated Control of Telomere DNA Topology as a Mechanism for Chromosome-End Protection SO MOLECULAR CELL LA English DT Article ID TOPOISOMERASE-II; DAMAGE RESPONSE; DYSFUNCTIONAL TELOMERES; PROTEINS TRF1; BINDING; LOOP; COMPLEX; DOMAIN; PROLIFERATION; LOCALIZATION AB The shelterin proteins protect telomeres against activation of the DNA damage checkpoints and recombinational repair. We show here that a dimer of the shelterin subunit TRF2 wraps similar to 90 bp of DNA through several lysine and arginine residues localized around its homodimerization domain. The expression of a wrapping-deficient TRF2 mutant, named Top-less, alters telomeric DNA topology, decreases the number of terminal loops (t-loops), and triggers the ATM checkpoint, while still protecting telomeres against non-homologous end joining (NHEJ). In Top-less cells, the protection against NHEJ is alleviated if the expression of the TRF2-interacting protein RAP1 is reduced. We conclude that a distinctive topological state of telomeric DNA, controlled by the TRF2-dependent DNA wrapping and linked to t-loop formation, inhibits both ATM activation and NHEJ. The presence of RAP1 at telomeres appears as a backup mechanism to prevent NHEJ when topology-mediated telomere protection is impaired. C1 [Benarroch-Popivker, Delphine; Pisano, Sabrina; Mendez-Bermudez, Aaron; Lototska, Liudmyla; Bauwens, Serge; Djerbi, Nadir; Latrick, Chrysa M.; Pei, Bei; Gay, Alexandre; Jaune, Emilie; Foucher, Kevin; Cherfils-Vicini, Julien; Gilson, Eric; Giraud-Panis, Marie-Josephe] Univ Nice Sophia Antipolis, CNRS UMR7284, INSERM U1081, Inst Res Canc & Aging,Nice IRCAN,Fac Med, F-06189 Nice, France. [Mendez-Bermudez, Aaron; Ye, Jing; Gilson, Eric] Shanghai Jiao Tong Univ, Pole Sino Francais Rech Sci Vivant & Genom, Int Lab Hematol & Canc, Ruijin Hosp,Sch Med,CNRS,INSERM,Nice Univ,Shangha, Shanghai 200025, Peoples R China. [Kaur, Parminder; Wang, Hong] N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA. [Fraisier, Vincent] UMR 144 CNRS Inst Curie, Nikon Imaging Ctr, Cell & Tissue Imaging Platform PICT IBiSA, F-75248 Paris 05, France. [Aeby, Eric] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res ISREC, Sch Life Sci, CH-1015 Lausanne, Switzerland. [Miron, Simona] Univ Paris 11, CNRS, CEA, Inst Integrat Biol Cell I2BC,CEA Saclay, F-91191 Gif Sur Yvette, France. [Londono-Vallejo, Arturo] Inst Curie, Telomeres & Canc Lab, UMR3244, F-75248 Paris, France. [Gilson, Eric] CHU Nice, Dept Genet, F-06202 Nice, France. [Gay, Alexandre] Univ Paris Diderot, CNRS UMR7212, INSERM UMR944, Sorbonne Paris Cite,Hop St Louis, 1 Ave Claude Vellefaux, F-75475 Paris 10, France. [Latrick, Chrysa M.] Univ Strasbourg, CNRS, INSERM, Dept Genom Fonct & Canc,Inst Genet & Biol Mol & C, 1 Rue Laurent Fries,BP 10142, F-67404 Illkirch Graffenstaden, France. [Miron, Simona] Inst Biochem, Splaiul Independentei 296, Bucharest 060031 17, Romania. [Aeby, Eric] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Aeby, Eric] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Gilson, E; Giraud-Panis, MJ (reprint author), Univ Nice Sophia Antipolis, CNRS UMR7284, INSERM U1081, Inst Res Canc & Aging,Nice IRCAN,Fac Med, F-06189 Nice, France.; Gilson, E (reprint author), Shanghai Jiao Tong Univ, Pole Sino Francais Rech Sci Vivant & Genom, Int Lab Hematol & Canc, Ruijin Hosp,Sch Med,CNRS,INSERM,Nice Univ,Shangha, Shanghai 200025, Peoples R China.; Gilson, E (reprint author), CHU Nice, Dept Genet, F-06202 Nice, France. EM eric.gilson@unice.fr; giraud-panis@unice.fr RI Wang, Hong/F-3164-2014; Aeby, Eric/A-4819-2017; Benarroch, Delphine/E-9983-2017; OI Wang, Hong/0000-0003-0165-3559; Aeby, Eric/0000-0002-0463-4444; Latrick, Chrysa/0000-0003-4497-7908 FU ARC; Conseil General 06 de la Region Provence Alpes-Cote d'Azur; FEDER; le Minitere de l'Enseignement Superieur; la region Provence Alpes-Cote d'Azur; l'INSERM; Fondation ARC; Ligue Contre le Cancer (EG Equipe labellise); ANR ("Teloloop'') [ANR-1582-30020690]; Institut Nationale du Cancer (INCa) (TELOCHROM); "Investments for the Future'' LABEX SIGNALIFE [ANR-11-LABX-0028-01]; NIH [NIH R01GM107559] FX We greatly thank Joachim Lingner for the HeLa cell line used in this study. This work was performed using the genomic, PICMI (supported by ARC and the Conseil General 06 de la Region Provence Alpes-Cote d'Azur), and CYTOMED (supported by FEDER, le Minitere de l'Enseignement Superieur, la region Provence Alpes-Cote d'Azur, and l'INSERM) facilities of IRCAN; we are very grateful for the help they provided. We are also indebted to Isabelle Zanella-Cleon for mass spectrometry analysis (Centre Commun de Micro-analyse des Proteines, IBCP Lyon). We acknowledge the PICT-IBiSA platform of the Institut Curie, member of the French National Research Infrastructure France-BioImaging (ANR-10-INSB-04). We are grateful to Matteo de Chiara and Silvia Bottini for the script of 2D probability density map on R. The AFM facility of PICMI was supported by the ARC and Conseil General 06 de la Region Provence Alpes-Cote d'Azur. This work was supported by grants from the Fondation ARC, Ligue Contre le Cancer (EG Equipe labellise), ANR ("Teloloop'' ANR-1582-30020690), Institut Nationale du Cancer (INCa) (TELOCHROM), "Investments for the Future'' LABEX SIGNALIFE (reference ANR-11-LABX-0028-01), and an NIH grant for DREEM experiments (NIH R01GM107559). NR 64 TC 15 Z9 15 U1 8 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD JAN 21 PY 2016 VL 61 IS 2 BP 274 EP 286 DI 10.1016/j.molcel.2015.12.009 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DG8HX UT WOS:000372325400010 PM 26774283 ER PT J AU Suh, H Ficarro, SB Kang, UB Chun, YJ Marto, JA Buratowski, S AF Suh, Hyunsuk Ficarro, Scott B. Kang, Un-Beom Chun, Yujin Marto, Jarrod A. Buratowski, Stephen TI Direct Analysis of Phosphorylation Sites on the Rpb1 C-Terminal Domain of RNA Polymerase II SO MOLECULAR CELL LA English DT Article ID CTD CODE; TRANSCRIPTION TERMINATION; KINASE; ELONGATION; RECRUITMENT; PHOSPHATASE; COMPLEX; CYCLE; CTK1 AB Dynamic interactions between RNA polymerase II and various mRNA-processing and chromatin-modifying enzymes are mediated by the changing phosphorylation pattern on the C-terminal domain (CTD) of polymerase subunit Rpb1 during different stages of transcription. Phosphorylations within the repetitive heptamer sequence (YSPTSPS) of CTD have primarily been defined using antibodies, but these do not distinguish different repeats or allow comparative quantitation. Using a CTD modified for mass spectrometry (msCTD), we show that Ser5-P and Ser2-P occur throughout the length of CTD and are far more abundant than other phosphorylation sites. msCTD extracted from cells mutated in several CTD kinases or phosphatases showed the expected changes in phosphorylation. Furthermore, msCTD associated with capping enzyme was enriched for Ser5-P while that bound to the transcription termination factor Rtt103 had higher levels of Ser2-P. These results suggest a relatively sparse and simple "CTD code.'' C1 [Suh, Hyunsuk; Ficarro, Scott B.; Kang, Un-Beom; Chun, Yujin; Marto, Jarrod A.; Buratowski, Stephen] Harvard Univ, Dept Biochem Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA. [Suh, Hyunsuk; Ficarro, Scott B.; Kang, Un-Beom; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Suh, Hyunsuk; Ficarro, Scott B.; Kang, Un-Beom; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. RP Buratowski, S (reprint author), Harvard Univ, Dept Biochem Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA. EM steveb@hms.harvard.edu FU DFCI/Blais Proteomics Center; NIH [GM56663] FX This work was supported by DFCI/Blais Proteomics Center support to J.A.M. and NIH grant GM56663 to S.B. We thank Mike Eck (HMS), Eun-Young Park (HMS), Craig Kaplan (Texas A&M), and Claire Moore (Tufts University) for materials; Byung-hoon Lee (HMS), Nahid Iglesias (HMS), Tim Sikorski (HMS), and Dane Hazelbaker (HMS) for technical advice; So-Young Hwang (HMS), J.A.M. lab members, and S.B. lab members for helpful discussions; and Dirk Eick for antibodies and discussion of unpublished results. NR 26 TC 15 Z9 15 U1 8 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD JAN 21 PY 2016 VL 61 IS 2 BP 297 EP 304 DI 10.1016/j.molcel.2015.12.021 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DG8HX UT WOS:000372325400012 PM 26799764 ER PT J AU Montalescot, G Sabatine, MS AF Montalescot, Gilles Sabatine, Marc S. TI Oral dual antiplatelet therapy: what have we learnt from recent trials? SO EUROPEAN HEART JOURNAL LA English DT Review DE Acute coronary syndromes; Stents; P2Y12 antagonists; Thienopyridines; Aspirin ID PERCUTANEOUS CORONARY INTERVENTION; ST-SEGMENT ELEVATION; ELUTING STENT IMPLANTATION; RANDOMIZED MULTICENTER TRIAL; PRIOR MYOCARDIAL-INFARCTION; CLOPIDOGREL PRETREATMENT; SECONDARY PREVENTION; PCI; PRASUGREL; EVENTS AB International guidelines recommend the use of aspirin treatment immediately and indefinitely in coronary patients. The optimal time to start and the duration of dual antiplatelet therapy (DAPT; aspirin plus a P2Y12 inhibitor) have not been clearly established. Recent clinical trials have provided important new information allowing for evidence-based decisions regarding timing of initiation and duration of DAPT. The benefit-to-risk ratio of DAPT pre-treatment appears to depend on the type of acute coronary syndrome, the time until angiography, and the onset of action of the drug. In stable patients undergoing percutaneous coronary intervention with the latest generation drug-eluting stents, patients should be treated for at least similar to 6 months. Shorter courses of therapy may be necessary when special conditions occur (e.g. surgery; oral anticoagulation). Longer courses of therapy may be reasonable in patients at low bleeding risk who are tolerating DAPT well. For patients with ACS, prolonged DAPT is beneficial and therefore reasonable as long as the patient is tolerating the therapy. Individualized management of DAPT must be seen as a dynamic prescription with regular re-evaluations of the risk-benefit to the patient according to changes in his/her clinical profile. C1 [Montalescot, Gilles] Univ Paris 06, Hop La Pitie Salpetriere, AP HP, ACT Study Grp,Inst Cardiol, F-75013 Paris, France. [Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. [Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA. RP Montalescot, G (reprint author), Univ Paris 06, Hop La Pitie Salpetriere, AP HP, ACT Study Grp,Inst Cardiol, F-75013 Paris, France. EM gilles.montalescot@psl.aphp.fr FU Acuitude; Amgen; AstraZeneca; Bayer; Berlin Chimie AG; Boehringer-Ingelheim; BMS; Brigham Women's Hospital; Cardiovascular Research Foundation; CME Resources; Conway; Daiichi-Sankyo; Eli-Lilly; Europa; Evidera; GLG; Hopitaux Universitaires Geneve; Lead-Up; McKinsey Company; Medcon International; Menarini; Medtronic; MSD; Pfizer; Sanofi-Aventis; Stentys; Medicines Company; TIMI Group; Universitat Basel; WebMD; Williams Connolly; Zoll Medical; ADIR; Celladon; Federation Francaise de Cardiologie; Gilead; ICAN; Janssen-Cilag; Recor; Alnylam; Cubist; CVS Caremark; Intarcia; Merck; Brigham and Women's Hospital from Abbott Laboratories; Critical Diagnostics; Eisai; GlaxoSmithKline; Roche Diagnostics; Takeda FX G.M. reports receiving consulting fees from Acuitude, Amgen, AstraZeneca, Bayer, Berlin Chimie AG, Boehringer-Ingelheim, BMS, Brigham Women's Hospital, Cardiovascular Research Foundation, CME Resources, Conway, Daiichi-Sankyo, Eli-Lilly, Europa, Evidera, GLG, Hopitaux Universitaires Geneve, Lead-Up, McKinsey & Company, Medcon International, Menarini, Medtronic, MSD, Pfizer, Sanofi-Aventis, Stentys, Medicines Company, TIMI Group, Universitat Basel, WebMD, Williams & Connolly, Zoll Medical and grant support from ADIR, Amgen, AstraZeneca, BMS, Celladon, Daiichi-Sankyo, Eli-Lilly, Federation Francaise de Cardiologie, Gilead, ICAN, Janssen-Cilag, Pfizer, Recor, Sanofi-Aventis, Stentys. M.S.S. reports receiving consulting fees from Alnylam, Amgen, AstraZeneca, Cubist, CVS Caremark, Intarcia, Merck (all <=$10 000 per year); and research grant support through Brigham and Women's Hospital from Abbott Laboratories; Amgen; AstraZeneca; Critical Diagnostics; Daiichi-Sankyo; Eisai; Gilead; GlaxoSmithKline; Intarcia; Merck; Roche Diagnostics; Sanofi-aventis; Takeda (All >$10 000 per year). NR 37 TC 7 Z9 8 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JAN 21 PY 2016 VL 37 IS 4 BP 344 EP 352 DI 10.1093/eurheartj/ehv377 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DE9RL UT WOS:000370975700012 PM 26248569 ER PT J AU Mauri, L Elmariah, S Yeh, RW Cutlip, DE Steg, PG Windecker, S Wiviott, SD Cohen, DJ Massaro, JM D'Agostino, RB Braunwald, E Kereiakes, DJ AF Mauri, Laura Elmariah, Sammy Yeh, Robert W. Cutlip, Donald E. Steg, P. Gabriel Windecker, Stephan Wiviott, Stephen D. Cohen, David J. Massaro, Joseph M. D'Agostino, Ralph B., Sr. Braunwald, Eugene Kereiakes, Dean J. CA DAPT Study Investigators TI Causes of late mortality with dual antiplatelet therapy after coronary stents SO EUROPEAN HEART JOURNAL LA English DT Article DE Dual antiplatelet therapy; Mortality; Cancer; Thienopyridine ID DRUG-ELUTING STENT; ACUTE MYOCARDIAL-INFARCTION; BARE METAL; CLOPIDOGREL USE; TRIALS; INTERVENTION; DURATION; REVASCULARIZATION; IMPLANTATION; METAANALYSIS AB Aims In the dual antiplatelet therapy (DAPT) study, continued thienopyridine beyond 12 months after drug-eluting stent placement was associated with increased mortality compared with placebo. We sought to evaluate factors related to mortality in randomized patients receiving either drug-eluting or bare metal stents in the DAPT study. Methods and results Patients were enrolled after coronary stenting, given thienopyridine and aspirin for 12 months, randomly assigned to continued thienopyridine or placebo for an additional 18 months (while taking aspirin), and subsequently treated with aspirin alone for another 3 months. A blinded independent adjudication committee evaluated deaths. Among 11 648 randomized patients, rates of all-cause mortality rates were 1.9 vs. 1.5% (continued thienopyridine vs. placebo, P = 0.07), cardiovascular mortality, 1.0 vs. 1.0% (P = 0.97), and non-cardiovascular mortality, 0.9 vs. 0.5% (P = 0.01) over the randomized period (Months 12-30). Rates of fatal bleeding were 0.2 vs. 0.1% (P = 0.81), and deaths related to any prior bleeding were 0.3 vs. 0.2% (P = 0.36), Months 12-33). Cancer incidence did not differ (2.0 vs. 1.6%, P = 0.12). Cancer-related deaths occurred in 0.6 vs. 0.3% (P = 0.02) and were rarely related to bleeding (0.1 vs. 0, P = 0.25). After excluding those occurring in patients with cancer diagnosed before enrolment, rates were 0.4 vs. 0.3% (P = 0.16). Conclusion Bleeding accounted for a minority of deaths among patients treated with continued thienopyridine. Cancer-related death in association with thienopyridine therapy was mainly not related to bleeding and may be a chance finding. Caution is warranted when considering extended thienopyridine in patients with advanced cancer. C1 [Mauri, Laura; Elmariah, Sammy; Yeh, Robert W.; Massaro, Joseph M.; D'Agostino, Ralph B., Sr.] Harvard Univ, Clin Res Inst, Clin Res Inst, Boston, MA USA. [Mauri, Laura; Wiviott, Stephen D.; Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. [Mauri, Laura; Elmariah, Sammy; Yeh, Robert W.; Cutlip, Donald E.; Wiviott, Stephen D.; Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA. [Elmariah, Sammy; Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Steg, P. Gabriel] AP HP, Dept Hosp Univ Fibrosis Inflammat & Remodeling, Paris, France. [Steg, P. Gabriel] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, Natl Heart & Lung Inst, London, England. [Windecker, Stephan] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Cohen, David J.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Cohen, David J.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA. [Massaro, Joseph M.; D'Agostino, Ralph B., Sr.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Braunwald, Eugene] Univ Paris Diderot, INSERM U1148, Hop Bichat, Paris, France. [Kereiakes, Dean J.] Christ Hosp, & Vasc Ctr, Lindner Ctr Res & Educ, Cincinnati, OH 45219 USA. RP Mauri, L (reprint author), Harvard Univ, Clin Res Inst, Clin Res Inst, Boston, MA USA.; Mauri, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA.; Mauri, L (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM lmauri1@partners.org FU Abbott; Boston Scientific; Cordis; Medtronic; Bristol-Myers Squibb Company/Sanofi Pharmaceuticals Partnership; Eli Lilly and Company; Daiichi Sankyo Company; US Department of Health and Human Services [1RO1FD003870-01] FX This work was supported by Abbott, Boston Scientific, Cordis, Medtronic, Bristol-Myers Squibb Company/Sanofi Pharmaceuticals Partnership, Eli Lilly and Company, and Daiichi Sankyo Company and the US Department of Health and Human Services (1RO1FD003870-01). NR 26 TC 13 Z9 13 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JAN 21 PY 2016 VL 37 IS 4 BP 378 EP 385 DI 10.1093/eurheartj/ehv614 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DE9RL UT WOS:000370975700017 PM 26586780 ER PT J AU Udell, JA Bonaca, MP Collet, JP Lincoff, AM Kereiakes, DJ Costa, F Lee, CW Mauri, L Valgimigli, M Park, SJ Montalescot, G Sabatine, MS Braunwald, E Bhatt, DL AF Udell, Jacob A. Bonaca, Marc P. Collet, Jean-Philippe Lincoff, A. Michael Kereiakes, Dean J. Costa, Francesco Lee, Cheol Whan Mauri, Laura Valgimigli, Marco Park, Seung-Jung Montalescot, Gilles Sabatine, Marc S. Braunwald, Eugene Bhatt, Deepak L. TI Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials SO EUROPEAN HEART JOURNAL LA English DT Article DE Dual antiplatelet therapy; Myocardial infarction; Stable coronary heart disease; Clopidogrel; Prasugrel; Ticagrelor ID ACUTE CORONARY SYNDROMES; ELUTING STENT IMPLANTATION; ASSOCIATION TASK-FORCE; ST-SEGMENT ELEVATION; PRACTICE GUIDELINES; AMERICAN-COLLEGE; ATHEROTHROMBOTIC EVENTS; NETWORK METAANALYSIS; CLINICAL-OUTCOMES; LATE CONSEQUENCES AB Aims Recent trials have examined the effect of prolonged dual antiplatelet therapy (DAPT) in a variety of patient populations, with heterogeneous results regarding benefit and safety, specifically with regard to cardiovascular and non-cardiovascular mortality. We performed a meta-analysis of randomized trials comparing more than a year of DAPT with aspirin alone in high-risk patients with a history of prior myocardial infarction (MI). Methods and results A total of 33 435 patients were followed over a mean 31 months among one trial of patients with prior MI (63.3% of total) and five trials with a subgroup of patients that presented with, or had a history of, a prior MI (36.7% of total). Extended DAPT decreased the risk of major adverse cardiovascular events compared with aspirin alone (6.4 vs. 7.5%; risk ratio, RR 0.78, 95% confidence intervals, CI, 0.67-0.90; P=0.001) and reduced cardiovascular death (2.3 vs. 2.6%; RR 0.85, 95% CI 0.74-0.98; P=0.03), with no increase in non-cardiovascular death (RR 1.03, 95% CI 0.86-1.23; P=0.76). The resultant effect on all-cause mortality was an RR of 0.92 (95% CI 0.83-1.03; P=0.13). Extended DAPT also reduced MI (RR 0.70, 95% CI 0.55-0.88; P=0.003), stroke (RR 0.81, 95% CI 0.68-0.97; P=0.02), and stent thrombosis (RR 0.50, 95% CI 0.28-0.89; P=0.02). There was an increased risk of major bleeding (1.85 vs. 1.09%; RR 1.73, 95% CI 1.19-2.50; P=0.004) but not fatal bleeding (0.14 vs. 0.17%; RR 0.91, 95% CI 0.53-1.58; P=0.75). Conclusion Compared with aspirin alone, DAPT beyond 1 year among stabilized high-risk patients with prior MI decreases ischaemic events, including significant reductions in the individual endpoints of cardiovascular death, recurrent MI, and stroke. Dual antiplatelet therapy beyond 1 year increases major bleeding, but not fatal bleeding or non-cardiovascular death. C1 [Udell, Jacob A.] Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Univ Hlth Network, Peter Munk Cardiac Ctr, 76 Grenville St, Toronto, ON M5S 1B1, Canada. [Udell, Jacob A.] Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Univ Hlth Network, Div Cardiovasc, 76 Grenville St, Toronto, ON M5S 1B1, Canada. [Udell, Jacob A.] Univ Toronto, Womens Coll Hosp, Womens Coll Res Inst, Toronto, ON M5S 1B1, Canada. [Udell, Jacob A.] Univ Toronto, Womens Coll Hosp, Dept Med, Div Cardiovasc, Toronto, ON M5S 1B1, Canada. [Bonaca, Marc P.; Sabatine, Marc S.; Braunwald, Eugene; Bhatt, Deepak L.] Harvard Univ, Sch Med, Brigham andWomens Hosp, TIMI Study Grp,Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. [Lincoff, A. Michael] Univ Paris 06, INSERM, Inst Cardiol, Hop La Pitie Salpetriere,AP HP,ACT Study Grp, Paris, France. [Lincoff, A. Michael] Cleveland Clin, Coordinating Ctr Clin Res, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Kereiakes, Dean J.] Christ Hosp, Heart & Vasc Ctr, Cincinnati, OH 45219 USA. [Kereiakes, Dean J.] Christ Hosp, Lindner Ctr Res & Educ, Cincinnati, OH 45219 USA. [Costa, Francesco; Valgimigli, Marco] Erasmus Med, Thoraxctr, NL-3015 CE Rotterdam, Netherlands. [Lee, Cheol Whan; Park, Seung-Jung] Univ Ulsan, Coll Med, Asan Med Ctr, Inst Heart, Seoul, South Korea. [Mauri, Laura] Harvard Univ, Brigham & Womens Hosp, Sch Med, Clin Res Inst, Boston, MA 02115 USA. [Mauri, Laura] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Valgimigli, Marco] Univ Hosp Bern, CH-3010 Bern, Switzerland. RP Udell, JA (reprint author), Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Univ Hlth Network, Peter Munk Cardiac Ctr, 76 Grenville St, Toronto, ON M5S 1B1, Canada.; Udell, JA (reprint author), Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Univ Hlth Network, Div Cardiovasc, 76 Grenville St, Toronto, ON M5S 1B1, Canada.; Udell, JA (reprint author), Univ Toronto, Womens Coll Hosp, Womens Coll Res Inst, Toronto, ON M5S 1B1, Canada.; Udell, JA (reprint author), Univ Toronto, Womens Coll Hosp, Dept Med, Div Cardiovasc, Toronto, ON M5S 1B1, Canada.; Bhatt, DL (reprint author), Harvard Univ, Sch Med, Brigham andWomens Hosp, TIMI Study Grp,Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM jay.udell@utoronto.ca; dlbhattmd@post.harvard.edu OI Costa, Francesco/0000-0002-3097-2834 FU Heart and Stroke Foundation of Canada; Women's College Research Institute and Department of Medicine, Women's College Hospital; Peter Munk Cardiac Centre, University Health Network; Department of Medicine and Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, University of Toronto FX There was no funding source for this study. Dr Udell was supported in part by the Heart and Stroke Foundation of Canada and Women's College Research Institute and Department of Medicine, Women's College Hospital; Peter Munk Cardiac Centre, University Health Network; Department of Medicine and Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, University of Toronto. NR 56 TC 53 Z9 55 U1 8 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JAN 21 PY 2016 VL 37 IS 4 BP 390 EP 399 DI 10.1093/eurheartj/ehv443 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DE9RL UT WOS:000370975700020 PM 26324537 ER PT J AU Magnani, G Storey, RF Steg, G Bhatt, DL Cohen, M Kuder, J Im, K Aylward, P Ardissino, D Isaza, D Parkhomenko, A Goudev, AR Dellborg, M Kontny, F Corbalan, R Medina, F Jensen, EC Held, P Braunwald, E Sabatine, MS Bonaca, MP AF Magnani, Giulia Storey, Robert F. Steg, Gabriel Bhatt, Deepak L. Cohen, Marc Kuder, Julia Im, Kyungah Aylward, Philip Ardissino, Diego Isaza, Daniel Parkhomenko, Alexander Goudev, Assen R. Dellborg, Mikael Kontny, Frederic Corbalan, Ramon Medina, Felix Jensen, Eva C. Held, Peter Braunwald, Eugene Sabatine, Marc S. Bonaca, Marc P. TI Efficacy and safety of ticagrelor for long-term secondary prevention of atherothrombotic events in relation to renal function: insights from the PEGASUS-TIMI 54 trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Ticagrelor; Myocardial infarction; Secondary prevention; Renal dysfunction ID CHRONIC KIDNEY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; GLOMERULAR-FILTRATION-RATE; ST-SEGMENT ELEVATION; OUTCOMES; CLOPIDOGREL; GUIDELINES; EQUATION; THERAPY AB Aims We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI). Methods and results Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with < 60 mL/min/1.73 m(2) pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR < 60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR < 60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. >= 60 (HR 0.88; 95% CI 0.77-1.00, P-interaction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR < 60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%). Conclusion In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor. C1 [Magnani, Giulia; Bhatt, Deepak L.; Kuder, Julia; Im, Kyungah; Braunwald, Eugene; Sabatine, Marc S.; Bonaca, Marc P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. [Magnani, Giulia; Bhatt, Deepak L.; Kuder, Julia; Im, Kyungah; Braunwald, Eugene; Sabatine, Marc S.; Bonaca, Marc P.] Harvard Univ, Sch Med, 75 Francis St, Boston, MA USA. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Steg, Gabriel] Hop Bichat Claude Bernard, DHU FIRE, Dept Cardiol, F-75877 Paris, France. [Steg, Gabriel] Univ Paris Diderot, Paris, France. [Steg, Gabriel] INSERM U1148, Paris, France. [Cohen, Marc] Rutgers New Jersey Med Sch, Dept Med, Div Cardiovasc, New York, NY USA. [Aylward, Philip] Flinders Univ S Australia, Cardiac & Crit Care Serv, Div Med, Adelaide, SA 5001, Australia. [Aylward, Philip] Med Ctr, Adelaide, SA, Australia. [Ardissino, Diego] Azienda Osped Univ Parma, Div Cardiovasc, Parma, Italy. [Isaza, Daniel] Fdn CardioInfantil, Bogota, Colombia. [Parkhomenko, Alexander] Ukranian Strazhesko Inst Cardiol, Kiev, Ukraine. [Goudev, Assen R.] Queen Giovanna Univ Hosp, Dept Cardiol, Sofia, Bulgaria. [Dellborg, Mikael] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med Cardiol, Gothenburg, Sweden. [Kontny, Frederic] Stavanger Univ Hosp, Dept Cardiol, Stavanger, Norway. [Corbalan, Ramon] Pontificia Univ Catolica Chile, Div Cardiovasc, Alameda 340, Santiago, Chile. [Medina, Felix] Hosp Nacl Cayetano Heredia, Lima, Peru. [Jensen, Eva C.; Held, Peter] AstraZenecaAZ R&D, Molndal, Sweden. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.; Bonaca, MP (reprint author), Harvard Univ, Sch Med, 75 Francis St, Boston, MA USA. EM mbonaca@partners.org FU AstraZeneca FX This study was supported by a grant from AstraZeneca. NR 18 TC 11 Z9 11 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JAN 21 PY 2016 VL 37 IS 4 BP 400 EP 408 DI 10.1093/eurheartj/ehv482 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DE9RL UT WOS:000370975700021 PM 26443023 ER PT J AU Golberg, A Bruinsma, BG Jaramillo, M Yarmush, ML Uygun, BE AF Golberg, Alexander Bruinsma, Bote G. Jaramillo, Maria Yarmush, Martin L. Uygun, Basak E. TI Rat liver regeneration following ablation with irreversible electroporation SO PEERJ LA English DT Article DE Liver regeneration; Irreversible electroporation; Liver ablation; Pulsed electric fields; Scarless regeneration; Progenitor cells; Hepatocytes ID PULSED ELECTRIC-FIELDS; STEM-CELLS; GROWTH-FACTORS; ADULT-RAT; PROGENITORS; EXPRESSION; PROLIFERATION; COMPARTMENT; CHALLENGES; CYTOKINES AB During the past decade, irreversible electroporation (IRE) ablation has emerged as a promising tool for the treatment of multiple diseases including hepatic cancer. However, the mechanisms behind the tissue regeneration following IRE ablation have not been investigated. Our results indicate that IRE treatment immediately kills the cells at the treatment site preserving the extracellular architecture, in effect causing in vivo decellularization. Over the course of 4 weeks, progenitor cell differentiation, through YAP and notch pathways, together with hepatocyte expansion led to almost complete regeneration of the ablated liver leading to the formation of hepatocyte like cells at the ablated zone. We did not observe significant scarring or tumor formation at the regenerated areas 6 months post IRE. Our study suggests a new model to study the regeneration of liver when the naive extracellular matrix is decellularized in vivo with completely preserved extracellular architecture. C1 [Golberg, Alexander; Bruinsma, Bote G.; Jaramillo, Maria; Yarmush, Martin L.; Uygun, Basak E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. [Golberg, Alexander; Bruinsma, Bote G.; Jaramillo, Maria; Yarmush, Martin L.; Uygun, Basak E.] Shriners Hosp Children, Boston, MA USA. [Golberg, Alexander] Tel Aviv Univ, Porter Sch Environm Studies, IL-69978 Tel Aviv, Israel. [Bruinsma, Bote G.] Univ Amsterdam, Acad Med Ctr, Dept Surg, Surg Lab, NL-1105 AZ Amsterdam, Netherlands. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Golberg, A; Uygun, BE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA.; Golberg, A; Uygun, BE (reprint author), Shriners Hosp Children, Boston, MA USA.; Golberg, A (reprint author), Tel Aviv Univ, Porter Sch Environm Studies, IL-69978 Tel Aviv, Israel. EM agolberg@gmail.com; buygun@mgh.harvard.edu FU Claflin Distinguished Scholar Award from Massachusetts General Hospital [2013A050726] FX This work was supported by the Claflin Distinguished Scholar Award from Massachusetts General Hospital (2013A050726) to Basak E. Uygun. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 2 Z9 2 U1 2 U2 8 PU PEERJ INC PI LONDON PA 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND SN 2167-8359 J9 PEERJ JI PeerJ PD JAN 21 PY 2016 VL 4 AR e1571 DI 10.7717/peerj.1571 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC7ML UT WOS:000369404300002 PM 26819842 ER PT J AU Ghita, M Coffey, CB Butterworth, KT McMahon, SJ Schettino, G Prise, KM AF Ghita, Mihaela Coffey, Caroline B. Butterworth, Karl T. McMahon, Stephen J. Schettino, Giuseppe Prise, Kevin M. TI Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE out-of-field effects; dose fractionation; cell survival; DNA damage ID BYSTANDER; IRRADIATION; CELL; THERAPY AB To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions. C1 [Ghita, Mihaela; Butterworth, Karl T.; McMahon, Stephen J.; Prise, Kevin M.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, 97 Lisburn Rd, Belfast BT7 9AE, Antrim, North Ireland. [Coffey, Caroline B.] Univ Nevada, Sch Med, Dept Pharmacol, Reno, NV 89557 USA. [Schettino, Giuseppe] Natl Phys Lab, Teddington TW11 0LW, Middx, England. [McMahon, Stephen J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [McMahon, Stephen J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ghita, M (reprint author), Queens Univ Belfast, Ctr Canc Res & Cell Biol, 97 Lisburn Rd, Belfast BT7 9AE, Antrim, North Ireland. EM m.ghita@qub.ac.uk RI Prise, Kevin/N-7872-2015 OI Prise, Kevin/0000-0001-6134-7946 FU Breast Cancer Campaign [2009MayPR03]; Cancer Research UK [C1513/A7047]; EU Marie Curie Fellowship [FP7-MC IOF-623630] FX The authors acknowledge the support of Breast Cancer Campaign (2009MayPR03) and Cancer Research UK (C1513/A7047). SJM is the holder of an EU Marie Curie Fellowship (FP7-MC IOF-623630). NR 19 TC 1 Z9 1 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2016 VL 61 IS 2 BP 515 EP 526 DI 10.1088/0031-9155/61/2/515 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA DC9BV UT WOS:000369516600008 PM 26683123 ER PT J AU Cai, WX Dhou, S Cifter, F Myronakis, M Hurwitz, MH Williams, CL Berbeco, RI Seco, J Lewis, JH AF Cai, Weixing Dhou, Salam Cifter, Fulya Myronakis, Marios Hurwitz, Martina H. Williams, Christopher L. Berbeco, Ross I. Seco, Joao Lewis, John H. TI 4D cone beam CT-based dose assessment for SBRT lung cancer treatment SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE 4D cone beam CT; SBRT; respiratory motion; treatment verification; dose assessment ID STEREOTACTIC BODY RADIOTHERAPY; 3D TUMOR-LOCALIZATION; X-RAY PROJECTION; MOTION MODEL; RESPIRATORY MOTION; EPID DOSIMETRY; MONTE-CARLO; IMAGE; VERIFICATION; FEASIBILITY AB The purpose of this research is to develop a 4DCBCT-based dose assessment method for calculating actual delivered dose for patients with significant respiratory motion or anatomical changes during the course of SBRT. To address the limitation of 4DCT-based dose assessment, we propose to calculate the delivered dose using time-varying ('fluoroscopic') 3D patient images generated from a 4DCBCT-based motion model. The method includes four steps: (1) before each treatment, 4DCBCT data is acquired with the patient in treatment position, based on which a patient-specific motion model is created using a principal components analysis algorithm. (2) During treatment, 2D time-varying kV projection images are continuously acquired, from which time-varying 'fluoroscopic' 3D images of the patient are reconstructed using the motion model. (3) Lateral truncation artifacts are corrected using planning 4DCT images. (4) The 3D dose distribution is computed for each timepoint in the set of 3D fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating deformed dose distributions. This approach is validated using six modified XCAT phantoms with lung tumors and different respiratory motions derived from patient data. The estimated doses are compared to that calculated using ground-truth XCAT phantoms. For each XCAT phantom, the calculated delivered tumor dose values generally follow the same trend as that of the ground truth and at most timepoints the difference is less than 5%. For the overall delivered dose, the normalized error of calculated 3D dose distribution is generally less than 3% and the tumor D95 error is less than 1.5%. XCAT phantom studies indicate the potential of the proposed method to accurately estimate 3D tumor dose distributions for SBRT lung treatment based on 4DCBCT imaging and motion modeling. Further research is necessary to investigate its performance for clinical patient data. C1 [Cai, Weixing; Dhou, Salam; Cifter, Fulya; Myronakis, Marios; Hurwitz, Martina H.; Williams, Christopher L.; Berbeco, Ross I.] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [Cai, Weixing; Dhou, Salam; Cifter, Fulya; Myronakis, Marios; Hurwitz, Martina H.; Williams, Christopher L.; Berbeco, Ross I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Seco, Joao] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Seco, Joao] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lewis, John H.] Calif State Univ Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA USA. RP Cai, WX (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA.; Cai, WX (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Lewis, JH (reprint author), Calif State Univ Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA USA. EM wcai@lroc.harvard.edu; jlewisphysics@gmail.com FU Varian Medical Systems, Inc.; Radiological Society of North America [RSCH1206] FX The authors would like to express their gratitude to Dr Seiko Nishioka of the Department of Radiology, NTT Hospital, Sapporo, Japan and Dr Hiroki Shirato of the Department of Radiation Medicine, Hokkaido University School of Medicine, Sapporo, Japan for sharing the 3D patient tumor position dataset with our group. This project was supported, in part, through a Master Research Agreement with Varian Medical Systems, Inc., Radiological Society of North America Research Scholar Grant No. RSCH1206 (J.H.L.) NR 31 TC 2 Z9 2 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2016 VL 61 IS 2 BP 554 EP 568 DI 10.1088/0031-9155/61/2/554 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA DC9BV UT WOS:000369516600011 PM 26683530 ER PT J AU Geng, CR Moteabbed, M Seco, J Gao, YM Xu, XG Ramos-Mendez, J Faddegon, B Paganetti, H AF Geng, Changran Moteabbed, Maryam Seco, Joao Gao, Yiming Xu, X. George Ramos-Mendez, Jose Faddegon, Bruce Paganetti, Harald TI Dose assessment for the fetus considering scattered and secondary radiation from photon and proton therapy when treating a brain tumor of the mother SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE proton therapy; Monte Carlo; computational phantom; fetus dose ID IONIZING-RADIATION; PEDIATRIC-PATIENTS; PRENATAL EXPOSURE; 2ND CANCERS; RADIOTHERAPY; PREGNANCY; NEUTRONS; IMRT; RISK; SIMULATION AB The goal of this work was to determine the scattered photon dose and secondary neutron dose and resulting risk for the sensitive fetus from photon and proton radiotherapy when treating a brain tumor during pregnancy. Anthropomorphic pregnancy phantoms with three stages (3-, 6-, 9-month) based on ICRP reference parameters were implemented in Monte Carlo platform TOPAS, to evaluate the scattered dose and secondary neutron dose and dose equivalent. To evaluate the dose equivalent, dose averaged quality factors were considered for neutrons. This study compared three treatment modalities: passive scattering and pencil beam scanning proton therapy (PPT and PBS) and 6-MV 3D conformal photon therapy. The results show that, for 3D conformal photon therapy, the scattered photon dose equivalent to the fetal body increases from 0.011 to 0.030 mSv per treatment Gy with increasing stage of gestation. For PBS, the neutron dose equivalent to the fetal body was significantly lower, i.e. increasing from 1.5 x 10(-3) to 2.5 x 10(-3) mSv per treatment Gy with increasing stage of gestation. For PPT, the neutron dose equivalent of the fetus decreases from 0.17 to 0.13 mSv per treatment Gy with the growing fetus. The ratios of dose equivalents to the fetus for a 52.2 Gy(RBE) course of radiation therapy to a typical CT scan of the mother's head ranged from 3.4-4.4 for PBS, 30-41 for 3D conformal photon therapy and 180-500 for PPT, respectively. The attained dose to a fetus from the three modalities is far lower than the thresholds of malformation, severe mental retardation and lethal death. The childhood cancer excessive absolute risk was estimated using a linear no-threshold dose-response relationship. The risk would be 1.0 (95% CI: 0.6, 1.6) and 0.1 (95% CI: -0.01, 0.52) in 105 for the 9-month fetus for PBS with a prescribed dose of 52.2 Gy(RBE). The increased risks for PPT and photon therapy are about two and one orders of magnitude larger than that for PBS, respectively. We can conclude that a pregnant woman with a brain tumor could be treated with pencil beam scanning with acceptable risks to the fetus. C1 [Geng, Changran; Moteabbed, Maryam; Seco, Joao; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Geng, Changran] Nanjing Univ Aeronaut & Astronaut, Dept Nucl Sci & Engn, Nanjing 210016, Jiangsu, Peoples R China. [Gao, Yiming; Xu, X. George] Rensselaer Polytech Inst, Nucl Engn Program, Troy, NY 12180 USA. [Ramos-Mendez, Jose; Faddegon, Bruce] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. [Moteabbed, Maryam; Seco, Joao; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Geng, CR; Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.; Geng, CR (reprint author), Nanjing Univ Aeronaut & Astronaut, Dept Nucl Sci & Engn, Nanjing 210016, Jiangsu, Peoples R China.; Paganetti, H (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM geng.chr@gmail.com; HPAGANETTI@mgh.harvard.edu FU China Scholarship Council (CSC); National Natural Science Foundation of China [11475087] FX CG was funded by the China Scholarship Council (CSC) and the National Natural Science Foundation of China (Grant No. 11475087). We would like to thank the MGH Monte Carlo group for many fruitful discussions and the Partners Research Computing group for maintaining the computer cluster. NR 41 TC 1 Z9 1 U1 2 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2016 VL 61 IS 2 BP 683 EP 695 DI 10.1088/0031-9155/61/2/683 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA DC9BV UT WOS:000369516600018 PM 26716718 ER PT J AU Yip, SSF Coroller, TP Sanford, NN Huynh, E Mamon, H Aerts, HJWL Berbeco, RI AF Yip, Stephen S. F. Coroller, Thibaud P. Sanford, Nina N. Huynh, Elizabeth Mamon, Harvey Aerts, Hugo J. W. L. Berbeco, Ross I. TI Use of registration-based contour propagation in texture analysis for esophageal cancer pathologic response prediction SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE esophageal cancer; PET; treatment response prediction; deformable registration; contour propagation ID DEFORMABLE IMAGE REGISTRATION; FDG-PET RADIOMICS; CUBIC B-SPLINE; F-18-FDG PET; UPTAKE HETEROGENEITY; INTRATUMORAL HETEROGENEITY; TUMOR HETEROGENEITY; RADIATION-THERAPY; TRACER UPTAKE; NECK TUMORS AB Change in PET-based textural features has shown promise in predicting cancer response to treatment. However, contouring tumour volumes on longitudinal scans is time-consuming. This study investigated the usefulness of contour propagation in texture analysis for the purpose of pathologic response prediction in esophageal cancer. Forty-five esophageal cancer patients underwent PET/CT scans before and after chemo-radiotherapy. Patients were classified into responders and non-responders after the surgery. Physician-defined tumour ROIs on pretreatment PET were propagated onto the post-treatment PET using rigid and ten deformable registration algorithms. PET images were converted into 256 discrete values. Co-occurrence, run-length, and size zone matrix textures were computed within all ROIs. The relative difference of each texture at different treatment time-points was used to predict the pathologic responders. Their predictive value was assessed using the area under the receiver-operating-characteristic curve (AUC). Propagated ROIs from different algorithms were compared using Dice similarity index (DSI). Contours propagated by the fast-demons, fast-free-form and rigid algorithms did not fully capture the high FDG uptake regions of tumours. Fast-demons propagated ROIs had the least agreement with other contours (DSI = 58%). Moderate to substantial overlap were found in the ROIs propagated by all other algorithms (DSI = 69%-79%). Rigidly propagated ROIs with co-occurrence texture failed to significantly differentiate between responders and non-responders (AUC = 0.58, q-value = 0.33), while the differentiation was significant with other textures (AUC = 0.71. 0.73, p < 0.009). Among the deformable algorithms, fast-demons (AUC = 0.68. 0.70, q-value < 0.03) and fast-free-form (AUC = 0.69. 0.74, q-value < 0.04) were the least predictive. ROIs propagated by all other deformable algorithms with any texture significantly predicted pathologic responders (AUC = 0.72. 0.78, q-value < 0.01). Propagated ROIs using deformable registration for all textures can lead to accurate prediction of pathologic response, potentially expediting the temporal texture analysis process. However, fast-demons, fast-free-form, and rigid algorithms should be applied with care due to their inferior performance compared to other algorithms. C1 [Yip, Stephen S. F.; Coroller, Thibaud P.; Sanford, Nina N.; Huynh, Elizabeth; Mamon, Harvey; Aerts, Hugo J. W. L.; Berbeco, Ross I.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [Yip, Stephen S. F.; Coroller, Thibaud P.; Sanford, Nina N.; Huynh, Elizabeth; Mamon, Harvey; Aerts, Hugo J. W. L.; Berbeco, Ross I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Yip, SSF (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM syip@lroc.harvard.edu RI Aerts, Hugo/P-6350-2015; OI Aerts, Hugo/0000-0002-2122-2003; Coroller, Thibaud/0000-0001-7662-8724 FU Brigham and Women's Hospital; National Institute of Health [U01CA190234, U24CA194354] FX This work is in part supported by the Kaye scholar grant from the Brigham and Women's Hospital. The authors would like to acknowledge the support from the National Institute of Health (U01CA190234 and U24CA194354). NR 74 TC 9 Z9 9 U1 1 U2 11 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2016 VL 61 IS 2 BP 906 EP 922 DI 10.1088/0031-9155/61/2/906 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA DC9BV UT WOS:000369516600031 PM 26738433 ER PT J AU Levman, J Takahashi, E AF Levman, Jacob Takahashi, Emi TI Multivariate Analyses Applied to Healthy Neurodevelopment in Fetal, Neonatal, and Pediatric MRI SO FRONTIERS IN NEUROANATOMY LA English DT Review DE multivariate analysis; machine learning; fetal; neonatal; pediatric; brain MRI ID BRAIN-DEVELOPMENT; FUNCTIONAL MRI; WHITE-MATTER; CEREBRAL-CORTEX; SEGMENTATION; CHILDREN; PREDICTION; NETWORKS; CONNECTIVITY; TRACTOGRAPHY AB Multivariate analysis (MVA) is a class of statistical and pattern recognition techniques that involve the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of neurological medical imaging related challenges including the evaluation of healthy brain development, the automated analysis of brain tissues and structures through image segmentation, evaluating the effects of genetic and environmental factors on brain development, evaluating sensory stimulation's relationship with functional brain activity and much more Compared to adult imaging, pediatric, neonatal and fetal imaging have attracted less attention from MVA researchers, however, recent years have seen remarkable MVA research growth in pre-adult populations. This paper presents the results of a systematic review of the literature focusing on MVA applied to healthy subjects in fetal, neonatal and pediatric magnetic resonance imaging (MRI) of the brain. While the results of this review demonstrate considerable interest from the scientific community in applications of MVA technologies in brain MRI, the field is still young and significant research growth will continue into the future. C1 [Levman, Jacob; Takahashi, Emi] Harvard Univ, Div Newborn Med, Dept Med, Boston Childrens Hosp,Sch Med, Boston, MA USA. [Levman, Jacob; Takahashi, Emi] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Levman, J (reprint author), Harvard Univ, Div Newborn Med, Dept Med, Boston Childrens Hosp,Sch Med, Boston, MA USA.; Levman, J (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM jacob.levman@chikkens.haward.edu FU National Institute of Health [R01HD078561, R03NS091587] FX This article was supported by the National Institute of Health grants R01HD078561 and R03NS091587 to ET. NR 121 TC 1 Z9 1 U1 1 U2 6 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5129 J9 FRONT NEUROANAT JI Front. Neuroanat. PD JAN 21 PY 2016 VL 9 AR 163 DI 10.3389/fnana.2015.00163 PG 15 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA DB3MG UT WOS:000368415100001 ER PT J AU Wang, H Kim, M Normoyle, KP Liano, D AF Wang, Huan Kim, Miri Normoyle, Kieran P. Liano, Daniel TI Thermal Regulation of the Brain-An Anatomical and Physiological Review for Clinical Neuroscientists SO FRONTIERS IN NEUROSCIENCE LA English DT Review DE neuroanatomy; cerebrovasculature; cerebral thermoregulation; carotid rete; cerebral circulation ID MIDDLE MENINGEAL ARTERY; CEREBRAL-BLOOD-FLOW; CEREBROSPINAL-FLUID FLOW; DURA-MATER; PIA MATER; TEMPERATURE; EVOLUTION; MAMMALS; HUMANS; HEAD AB Humans, like all mammals and birds, maintain a near constant core body temperature of 36-37.5 degrees C over a broad range of environmental conditions and are thus referred to as endothermy. The evolution of the brain and its supporting structures in mammals and birds coincided with this development of endothermy. Despite the recognition that a more evolved and complicated brain with all of its temperature-dependent cerebral circuitry and neuronal processes would require more sophisticated thermal control mechanisms, the current understanding of brain temperature regulation remains limited. To optimize the development and maintenance of the brain in health and to accelerate its healing and restoration in illness, focused, and committed efforts are much needed to advance the fundamental understanding of brain temperature. To effectively study and examine brain temperature and its regulation, we must first understand relevant anatomical and physiological properties of thermoregulation in the head-neck regions. C1 [Wang, Huan] Carle Fdn Hosp, Dept Neurosurg, Urbana, IL USA. [Wang, Huan] Univ Illinois, Beckman Inst, Thermal Neurosci Lab, Urbana, IL 61801 USA. [Wang, Huan; Kim, Miri; Normoyle, Kieran P.] Univ Illinois, Coll Med, Urbana, IL 61801 USA. [Kim, Miri] Univ Illinois, Neurosci Program, Urbana, IL 61801 USA. [Kim, Miri] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA. [Normoyle, Kieran P.; Liano, Daniel] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. [Normoyle, Kieran P.] Massachusetts Gen Hosp, Dept Child Neurol, Boston, MA 02114 USA. [Liano, Daniel] Univ Illinois, Beckman Inst, NeuroTech Grp, Urbana, IL 61801 USA. [Liano, Daniel] Cade Fdn Hosp, Dept Neurol, Urbana, IL USA. RP Wang, H (reprint author), Carle Fdn Hosp, Dept Neurosurg, Urbana, IL USA.; Wang, H (reprint author), Univ Illinois, Beckman Inst, Thermal Neurosci Lab, Urbana, IL 61801 USA.; Wang, H (reprint author), Univ Illinois, Coll Med, Urbana, IL 61801 USA. EM huanwang@illinois.edu NR 57 TC 0 Z9 0 U1 3 U2 10 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD JAN 21 PY 2016 VL 9 AR 528 DI 10.3389/fnins.2015.00528 PG 6 WC Neurosciences SC Neurosciences & Neurology GA DB5WV UT WOS:000368585300002 ER PT J AU Kilcoyne, A Kaplan, JL Gee, MS AF Kilcoyne, Aoife Kaplan, Jess L. Gee, Michael S. TI Inflammatory bowel disease imaging: current practice and future directions SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Imaging; Inflammatory bowel disease; Crohn's disease; Ulcerative colitis; Computed tomography; Magnetic resonance imaging ID MAGNETIC-RESONANCE ENTEROCLYSIS; DUAL-ENERGY CT; CROHNS-DISEASE; MR ENTEROGRAPHY; CONVENTIONAL ENTEROCLYSIS; ABDOMINAL TUBERCULOSIS; ULCERATIVE-COLITIS; CLINICAL-COURSE; FOLLOW-UP; WALL INFLAMMATION AB The purpose of this paper is to evaluate the role of imaging in inflammatory bowel disease (IBD), including detection of extraluminal complications and extraintestinal manifestations of IBD, assessment of disease activity and treatment response, and discrimination of inflammatory from fibrotic strictures. IBD is a chronic idiopathic disease affecting the gastrointestinal tract that is comprised of two separate, but related intestinal disorders; Crohn's disease and ulcerative colitis. The paper discusses, in detail the pros and cons of the different IBD imaging modalities that need to be considered in order to optimize the imaging and clinical evaluation of patients with IBD. Historically, IBD evaluation of the bowel has included imaging to assess the portions of the small bowel that are inaccessible to optical endoscopic visualization. This traditionally was performed using barium fluoroscopic techniques; however, cross-sectional imaging techniques (computed tomography and magnetic resonance imaging) are being increasingly utilized for IBD evaluation because they can simultaneously assess mural and extramural IBD manifestations. Recent advances in imaging technology, that continue to improve the ability of imaging to noninvasively follow disease activity and treatment response, are also discussed. This review article summarizes the current imaging approach in inflammatory bowel disease as well as the role of emerging imaging modalities. C1 [Kilcoyne, Aoife; Gee, Michael S.] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02214 USA. [Kaplan, Jess L.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02214 USA. RP Kilcoyne, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02214 USA. EM akilcoyne1@mgh.harvard.edu NR 122 TC 1 Z9 1 U1 1 U2 2 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JAN 21 PY 2016 VL 22 IS 3 BP 917 EP 932 DI 10.3748/wjg.v22.i3.917 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB5KD UT WOS:000368552100003 PM 26811637 ER PT J AU Shu, SK Lin, CY He, HH Witwicki, RM Tabassum, DP Roberts, JM Janiszewska, M Huh, SJ Liang, Y Ryan, J Doherty, E Mohammed, H Guo, H Stover, DG Ekram, MB Peluffo, G Brown, J D'Santos, C Krop, IE Dillon, D McKeown, M Ott, C Qi, J Ni, M Rao, PK Duarte, M Wu, SY Chiang, CM Anders, L Young, RA Winer, EP Letai, A Barry, WT Carroll, JS Long, HW Brown, M Liu, XS Meyer, CA Bradner, JE Polyak, K AF Shu, Shaokun Lin, Charles Y. He, Housheng Hansen Witwicki, Robert M. Tabassum, Doris P. Roberts, Justin M. Janiszewska, Michalina Huh, Sung Jin Liang, Yi Ryan, Jeremy Doherty, Ernest Mohammed, Hisham Guo, Hao Stover, Daniel G. Ekram, Muhammad B. Peluffo, Guillermo Brown, Jonathan D'Santos, Clive Krop, Ian E. Dillon, Deborah McKeown, Michael Ott, Christopher Qi, Jun Ni, Min Rao, Prakash K. Duarte, Melissa Wu, Shwu-Yuan Chiang, Cheng-Ming Anders, Lars Young, Richard A. Winer, Eric P. Letai, Antony Barry, William T. Carroll, Jason S. Long, Henry W. Brown, Myles Liu, X. Shirley Meyer, Clifford A. Bradner, James E. Polyak, Kornelia TI Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer SO NATURE LA English DT Article ID SUPER-ENHANCERS; SELECTIVE-INHIBITION; CELL IDENTITY; RNA-SEQ; C-MYC; INFLAMMATION; STRATEGY; LEUKEMIA; SUBTYPES; PP2A AB Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy(1-3). BET bromodomain inhibitors, which have shown efficacy in several models of cancer(4-6), have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs(7-9). Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance. C1 [Shu, Shaokun; Lin, Charles Y.; He, Housheng Hansen; Witwicki, Robert M.; Tabassum, Doris P.; Roberts, Justin M.; Janiszewska, Michalina; Huh, Sung Jin; Ryan, Jeremy; Doherty, Ernest; Stover, Daniel G.; Ekram, Muhammad B.; Peluffo, Guillermo; Brown, Jonathan; Krop, Ian E.; Dillon, Deborah; McKeown, Michael; Ott, Christopher; Qi, Jun; Ni, Min; Winer, Eric P.; Letai, Antony; Long, Henry W.; Brown, Myles; Bradner, James E.; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Shu, Shaokun; Lin, Charles Y.; He, Housheng Hansen; Witwicki, Robert M.; Janiszewska, Michalina; Huh, Sung Jin; Ryan, Jeremy; Stover, Daniel G.; Ekram, Muhammad B.; Peluffo, Guillermo; Brown, Jonathan; Krop, Ian E.; McKeown, Michael; Ott, Christopher; Qi, Jun; Ni, Min; Winer, Eric P.; Letai, Antony; Barry, William T.; Brown, Myles; Bradner, James E.; Polyak, Kornelia] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Shu, Shaokun; Lin, Charles Y.; He, Housheng Hansen; Witwicki, Robert M.; Janiszewska, Michalina; Huh, Sung Jin; Ryan, Jeremy; Stover, Daniel G.; Ekram, Muhammad B.; Peluffo, Guillermo; Brown, Jonathan; Krop, Ian E.; McKeown, Michael; Ott, Christopher; Qi, Jun; Ni, Min; Winer, Eric P.; Letai, Antony; Barry, William T.; Brown, Myles; Bradner, James E.; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [He, Housheng Hansen; Guo, Hao; Barry, William T.; Liu, X. Shirley; Meyer, Clifford A.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [He, Housheng Hansen; Guo, Hao; Barry, William T.; Liu, X. Shirley; Meyer, Clifford A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [He, Housheng Hansen; Liang, Yi] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada. [He, Housheng Hansen] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. [Doherty, Ernest] Harvard Univ, Cambridge, MA 02138 USA. [Mohammed, Hisham; D'Santos, Clive; Carroll, Jason S.] Univ Cambridge, Cambridge Inst, Canc Res UK, Cambridge CB2 0RE, England. [Dillon, Deborah] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Dillon, Deborah] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Rao, Prakash K.; Duarte, Melissa; Long, Henry W.; Brown, Myles; Liu, X. Shirley; Polyak, Kornelia] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Wu, Shwu-Yuan; Chiang, Cheng-Ming] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dept Biochem, Dallas, TX 75390 USA. [Wu, Shwu-Yuan; Chiang, Cheng-Ming] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dept Pharmacol, Dallas, TX 75390 USA. [Anders, Lars; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Liu, X. Shirley; Bradner, James E.; Polyak, Kornelia] Broad Inst, Cambridge, MA 02142 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM james_bradner@dfci.harvard.edu; kornelia_polyak@dfci.harvard.edu RI Young, Richard/F-6495-2012; OI Young, Richard/0000-0001-8855-8647; Stover, Daniel/0000-0001-9003-8165; Brown, Myles/0000-0002-8213-1658 FU NIH DF/HCC SPORE in Breast Cancer [CA168504, CA080111, CA103867]; Susan G. Komen Foundation; CPRIT [RP110471, RP140367]; Welch Foundation; US Department of Defense CDMRP [BC122003, CA120184]; Princess Margaret Cancer Foundation; Canada Foundation for Innovation; Ontario Research Fund [CFI32372]; NSERC discovery grant [RGPIN-2015-04658]; Harvard Ludwig Center for Cancer Research FX We thank D. Silver and members of the Polyak and Bradner laboratories for their critical reading of this manuscript and useful discussions. We thank G. Brown for help with creating the word cloud figures. This work was supported by the NIH DF/HCC SPORE in Breast Cancer CA168504 (K.P., E.P.W., I.E.K., D.D., W.T.B., and J.E.B.), CA080111 (K.P. and M.B.), and CA103867 (C.M.C.), Susan G. Komen Foundation (S.S.), CPRIT RP110471 and RP140367 (C.M.C), Welch Foundation (C.M.C.), US Department of Defense CDMRP BC122003 (S.X.L.) and CA120184 (C.Y.L.), Princess Margaret Cancer Foundation (H.H.H.), Canada Foundation for Innovation and Ontario Research Fund CFI32372 (H.H.H.), NSERC discovery grant RGPIN-2015-04658 (H.H.H.), and the Harvard Ludwig Center for Cancer Research (J.E.B., M.B. and K.P.). NR 36 TC 33 Z9 33 U1 25 U2 62 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 21 PY 2016 VL 529 IS 7586 BP 413 EP + DI 10.1038/nature16508 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB2QT UT WOS:000368354800050 PM 26735014 ER PT J AU Powers, BW Chaguturu, SK AF Powers, Brian W. Chaguturu, Sreekanth K. TI ACOs and High-Cost Patients SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Powers, Brian W.; Chaguturu, Sreekanth K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Powers, Brian W.] Harvard Univ, Sch Business, Boston, MA 02115 USA. [Chaguturu, Sreekanth K.] Partners HealthCare, Boston, MA USA. [Chaguturu, Sreekanth K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Powers, BW (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 4 TC 5 Z9 5 U1 2 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 21 PY 2016 VL 374 IS 3 BP 203 EP 205 DI 10.1056/NEJMp1511131 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DB3IS UT WOS:000368404800003 PM 26789867 ER EF