FN Thomson Reuters Web of Science™ VR 1.0 PT J AU McCarthy, AL Winters, ME Busch, DR Gonzalez-Giraldo, E Ko, TS Lynch, JM Schwab, PJ Xiao, R Buckley, EM Vossough, A Licht, DJ AF McCarthy, Ann L. Winters, Madeline E. Busch, David R. Gonzalez-Giraldo, Ernesto Ko, Tiffany S. Lynch, Jennifer M. Schwab, Peter J. Xiao, Rui Buckley, Erin M. Vossough, Arastoo Licht, Daniel J. TI Scoring system for periventricular leukomalacia in infants with congenital heart disease SO PEDIATRIC RESEARCH LA English DT Article ID WHITE-MATTER INJURY; BRAIN-INJURY; SURGERY; NEWBORNS; DEFECTS AB BACKGROUND: Currently two magnetic resonance imaging (MRI) methods have been used to assess periventricular leukomalacia (PVL) severity in infants with congenital heart disease: manual volumetric lesion segmentation and an observational categorical scale. Volumetric classification is labor intensive and the categorical scale is quick but unreliable. We propose the quartered point system (QPS) as a novel, intuitive, time-efficient metric with high interrater agreement. METHODS: QPS is an observational scale that asks the rater to score MRIs on the basis of lesion size, number, and distribution. Pre- and postoperative, brain MRIs were obtained on term congenital heart disease infants. Three independent observers scored PVL severity using all three methods: volumetric segmentation, categorical scale, and QPS. RESULTS: One-hundred and thirty-five MR's were obtained from 72 infants; PVL was seen in 48 MRIs. Volumetric measurements among the three raters were highly concordant (pc = 0.94-0.96). Categorical scale severity scores were in poor agreement between observers (K = 0.17) and fair agreement with volumetrically determined severity (K = 0.26). QPS scores were in very good agreement between observers (K = 0.82) and with volumetric severity (K = 0.81). CONCLUSION: QPS minimizes training and sophisticated radiologic analysis and increases interrater reliability. QPS offers greater sensitivity to stratify PVL severity and has the potential to more accurately correlate with neurodevelopmental outcomes. C1 [McCarthy, Ann L.; Winters, Madeline E.; Busch, David R.; Schwab, Peter J.; Licht, Daniel J.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Busch, David R.; Lynch, Jennifer M.] Univ Penn, Dept Phys, Philadelphia, PA 19104 USA. [Busch, David R.; Lynch, Jennifer M.] Univ Penn, Dept Astron, Philadelphia, PA 19104 USA. [Gonzalez-Giraldo, Ernesto] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ko, Tiffany S.] Univ Penn, Bioengn, Philadelphia, PA 19104 USA. [Xiao, Rui] Univ Penn, Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Buckley, Erin M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Opt Div,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Vossough, Arastoo] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. RP McCarthy, AL (reprint author), Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. EM annlynnmccarthy@gmail.com FU National Heart, Lung and Blood Institute, Bethesda, MD [HL007915]; Thrasher Research Foundation Early Career Award, Salt Lake City, UT; National Institutes of Health T32, Bethesda, MD [HL007954]; June and Steve Wolfson Family Foundation, Philadelphia, PA; National Institutes of Health, Bethesda, MD [NS-072338]; Student Scholarship in Cerebrovascular Disease and Stroke at the American Heart Association's Stroke Council, Dallas,TX FX This study was supported by: a 2013 Student Scholarship in Cerebrovascular Disease and Stroke at the American Heart Association's Stroke Council, Dallas,TX (A.L.M.); National Heart, Lung and Blood Institute HL007915, Bethesda, MD (D.R.B.);Thrasher Research Foundation Early Career Award, Salt Lake City, UT (D.R.B.); National Institutes of Health T32 grant no. HL007954, Bethesda, MD (J.M.L.); National Institutes of Health grant no. NS-072338, Bethesda, MD (D.J.L.); and the June and Steve Wolfson Family Foundation, Philadelphia, PA (D.J.L.). NR 22 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 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 2015 VL 78 IS 3 BP 304 EP 309 DI 10.1038/pr.2015.99 PG 6 WC Pediatrics SC Pediatrics GA CP3BT UT WOS:000359752500010 PM 25996891 ER PT J AU Luo, C Pietruska, JR Sheng, JH Bronson, RT Hu, MFG Cui, RT Hinds, PW AF Luo, Chi Pietruska, Jodie R. Sheng, Jinghao Bronson, Roderick T. Hu, Miaofen G. Cui, Rutao Hinds, Philip W. TI Expression of oncogenic BRAF(V600E) in melanocytes induces Schwannian differentiation invivo SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Letter ID MELANOMA; MICE; GROWTH; ARREST; CELLS; NEVUS C1 [Luo, Chi; Hinds, Philip W.] Tufts Univ, Sackler Sch Grad Biomed Sci, Grad Program Genet, Boston, MA 02111 USA. [Luo, Chi; Pietruska, Jodie R.; Sheng, Jinghao; Hu, Miaofen G.; Hinds, Philip W.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA USA. [Pietruska, Jodie R.; Hinds, Philip W.] Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. [Sheng, Jinghao] Zhejiang Univ, Sch Med, Inst Environm Med, Hangzhou 310003, Zhejiang, Peoples R China. [Bronson, Roderick T.] Dana Farber Harvard Canc Ctr, Rodent Histopathol Core, Boston, MA USA. [Cui, Rutao] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02118 USA. RP Hinds, PW (reprint author), Tufts Univ, Sackler Sch Grad Biomed Sci, Grad Program Genet, Boston, MA 02111 USA. EM phil.hinds@tufts.edu FU NCI NIH HHS [CA095798, R01 CA095798] NR 11 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 EI 1755-148X J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD SEP PY 2015 VL 28 IS 5 BP 603 EP 606 DI 10.1111/pcmr.12384 PG 4 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA CP3WG UT WOS:000359812800011 PM 26036358 ER PT J AU Singh, JA Ramachandran, R AF Singh, Jasvinder A. Ramachandran, Rekha TI Are there racial disparities in utilization and outcomes after total elbow arthroplasty? SO RHEUMATOLOGY INTERNATIONAL LA English DT Article DE Racial disparities; Total elbow arthroplasty; Race; Utilization; Outcomes; Mortality; Discharge; Hospital stay ID UNITED-STATES; HIP-REPLACEMENT; TOTAL SHOULDER; VOLUME; TRENDS AB The aim of the study was to assess racial disparities in utilization rates and outcomes after primary total elbow arthroplasty (TEA). We used the National Inpatient Sample from 1998 to 2010, a US national database. Patient characteristics, comorbidity and outcomes after TEA were assessed over time and differences by race studied over the study period. Cochran-Armitage test was used for time trends and logistic regression for the comparison of outcomes by race. In 1998, TEA utilization rate was 0.38/100,000 in Whites and 0.24/100,000 in Blacks (p = 0.002); in 2010, it was 0.91 and 0.59/100,000, respectively (p < 0.0001). White-Black disparity in TEA utilization was significant across 13 years (p = 0.03). Compared with White patients, Black patients undergoing TEA were younger (61.9 vs. 52 years; p < 0.0001), less likely to be female (70.6 vs. 61.4 %; p = 0.0007) and more likely to have rheumatoid arthritis as the underlying diagnosis (13.0 vs. 17.2 %; p = 0.036). Mortality was rare, 0.26 % in Blacks and 0.32 % in Whites (p = 0.83). Discharge to an inpatient facility was higher in White versus Black patients in unadjusted analyses (16.8 vs. 10.4 %; p = 0.003), but in analyses adjusted for age, sex, Deyo-Charlson index and the underlying diagnosis, the differences were no longer significant (p = 0.79). The length of hospital stay greater than the median stay was noted in 29.8 % Whites versus 31.2 % Blacks, respectively (p = 0.61). There was no evidence of White-Black disparity in hospital length of stay in 1998-2000 (p = 0.66) or 2009-2010 (p = 0.59) periods. In this study, we found persisting racial disparities in TEA utilization rates. No White-Black disparities were noted in TEA outcomes, except slight differences in discharge disposition. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Ramachandran, Rekha] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. EM Jasvinder.md@gmail.com FU Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Institute of Aging (NIA); National Cancer Institute (NCI) FX This material is the result of work supported by the resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institute of Aging (NIA) and National Cancer Institute (NCI). NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0172-8172 EI 1437-160X J9 RHEUMATOL INT JI Rheumatol. Int. PD SEP PY 2015 VL 35 IS 9 BP 1479 EP 1487 DI 10.1007/s00296-015-3252-y PG 9 WC Rheumatology SC Rheumatology GA CP4EG UT WOS:000359834200004 PM 25812536 ER PT J AU Quinzanos, I Hirsh, JM Bright, C Caplan, L AF Quinzanos, Itziar Hirsh, Joel M. Bright, Christina Caplan, Liron TI Cross-sectional correlation of single-item health literacy screening questions with established measures of health literacy in patients with rheumatoid arthritis SO RHEUMATOLOGY INTERNATIONAL LA English DT Article DE Rheumatoid arthritis; Health literacy; Patient outcome assessment; Vulnerable populations ID ASSOCIATION; HOSPITALS; OUTCOMES; ADULTS; SKILLS AB Research suggests that health literacy (HL) is associated with rheumatoid arthritis (RA) patients' functional status. Single-item health literacy screening (SILS) questionnaires may establish patients' HL; however, the wording of SILS may be misinterpreted by RA patients as a query regarding physical limitations. Despite this threat to validity, multiple publications have employed the SILSs as a measure of health literacy. We assessed the construct validity of two SILS's versions by correlating scores with standardized HL measures. English-speaking adult RA patients at a hospital serving low-income patients were enrolled in a cross-sectional study. Subjects completed two SILS versions, as well as two longer HL measurement tools [short test of functional health literacy in adults (s-TOFHLA) and the rapid estimate of adult literacy in medicine (REALM)]. Spearman correlation was used to compare these tools. The study enrolled 110 subjects. There was a good correlation between the two SILS versions (r = 0.705). The correlation of SILS2 and REALM or s-TOFHLA was less robust. The distribution of scores within each SILS2 category demonstrated substantial variation. The SILS2 has construct validity in the assessment of HL in patients with RA, though its correlation with traditional methods of assessing HL is weak. C1 [Quinzanos, Itziar; Caplan, Liron] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. [Quinzanos, Itziar; Hirsh, Joel M.; Bright, Christina; Caplan, Liron] Univ Colorado, Sch Med, Dept Med, Div Rheumatol, Aurora, CO 80045 USA. [Hirsh, Joel M.] Denver Hlth Med Ctr, Dept Internal Med, Div Rheumatol, Denver, CO 80204 USA. RP Quinzanos, I (reprint author), Denver Vet Affairs Med Ctr, Dept Med, 1055 Clermont St,Res A151, Denver, CO 80220 USA. EM itziar.quinzanos@ucdenver.edu; Joel.Hirsh@dhha.org; Christina.m.bright@gmail.com; Liron.Caplan@ucdenver.edu FU VA HSR&D Career Development Award [07-221, 09-388] FX Dr. Caplan is supported by a VA HSR&D Career Development Award (07-221 and 09-388). The funding sources had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 22 TC 1 Z9 1 U1 2 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0172-8172 EI 1437-160X J9 RHEUMATOL INT JI Rheumatol. Int. PD SEP PY 2015 VL 35 IS 9 BP 1497 EP 1502 DI 10.1007/s00296-015-3238-9 PG 6 WC Rheumatology SC Rheumatology GA CP4EG UT WOS:000359834200006 PM 25744280 ER PT J AU Amri, R Bordeianou, LG Sylla, P Berger, DL AF Amri, Ramzi Bordeianou, Liliana G. Sylla, Patricia Berger, David L. TI Renewed assessment of the stapled anastomosis with the increasing role of laparoscopic colectomy for colon cancer SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Colonic neoplasms; Laparoscopic surgery; Stapled anastomosis; Surgical complications ID ANTERIOR RESECTION; RECURRENCE; CARCINOMA; SURGERY; RECTUM; TRIAL AB Stapled gastrointestinal anastomosis has gained wide adoption among the surgical community for its ease, speed, and its applicability in laparoscopic surgery. Over the last decade, with the increase in laparoscopic techniques in colon surgery, anastomotic stapling has become the technique of choice for colon cancer surgery at our center. This abstract assesses whether the increasing adoption of anastomotic stapling affected the rate of anastomotic leaks and duration of surgery. All patients surgically treated for colon cancer with a primary bowel anastomosis from 2004 through 2011 were included (n = 998). Duration of stay, surgery, and postoperative complication rates was compared between hand-sewn and stapled anastomosis. The number of stapled anastomoses grew significantly from 45.8 % in 2004-2007 to 80.3 % in 2008-2011 (p < 0.001), and an increasing portion of those is performed in laparoscopic procedures (29.8 to 43.3 %; p = 0.01). Surgeries using stapled anastomosis initially took longer, but a decreasing trend (2004-2007: 147.5 min to 2007-2011: 124 min; p < 0.001) along with an increasing duration in hand-sewn surgeries (94-118.5 min; p < 0.01) meant stapled procedures became shorter than hand-sewn procedures by 2009. Complication rates did not differ significantly between groups, with stapled anastomoses having lower percentages of anastomotic leaks (1.6 vs. 2.4 %; p = 0.38). By the second half of our research period, the median admission for patients with stapled anastomoses was two days shorter (4 vs. 6 days; p < 0.001), independently of the chosen approach. Stapled anastomoses did not increase anastomotic leak rates. If anything, leak rates appeared slightly lower. In addition, stapled anastomoses significantly shortened operation duration. With the benefit of being a tool that facilitates minimally invasive surgery, it is a safe way to improve efficiency, reduce costs, and promote faster and better recovery. C1 [Amri, Ramzi; Bordeianou, Liliana G.; Sylla, Patricia; Berger, David L.] Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. [Amri, Ramzi; Bordeianou, Liliana G.; Sylla, Patricia; Berger, David L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 15 Parkman St, Boston, MA 02114 USA. EM dberger@mgh.harvard.edu OI Amri, Ramzi/0000-0001-7416-6650 FU Harvard Catalyst / The Harvard Clinical and Translational Science Center (National Center for Research Resources, National Institutes of Health); Harvard Catalyst / The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard University; Dutch Cancer Society; Dutch Digestive Society; Amsterdam University Funds; Fulbright Foundation FX This work was conducted with support from Harvard Catalyst / The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 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.) This work was also supported by the Dutch Cancer Society, the Dutch Digestive Society, the Amsterdam University Funds, and the Fulbright Foundation. (all funding: RA) NR 9 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD SEP PY 2015 VL 29 IS 9 BP 2675 EP 2682 DI 10.1007/s00464-014-3989-5 PG 8 WC Surgery SC Surgery GA CP6PG UT WOS:000360009100031 PM 25472748 ER PT J AU Stanford, FC Jones, DB Schneider, BE Blackburn, GL Apovian, CM Hess, DT Chiodi, S Robert, S Bourland, AC Wee, CC AF Stanford, Fatima Cody Jones, Daniel B. Schneider, Benjamin E. Blackburn, George L. Apovian, Caroline M. Hess, Donald T. Chiodi, Sarah Robert, Shirley Bourland, Ashley C. Wee, Christina C. TI Patient race and the likelihood of undergoing bariatric surgery among patients seeking surgery SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Bariatric surgery; Obesity; Insurance coverage; Vulnerable populations; Social class; Ethnic minorities ID WEIGHT-LOSS; OBESITY; TRENDS; DISPARITIES AB Ethnic minority adults have disproportionately higher rates of obesity than Caucasians but are less likely to undergo bariatric surgery. Recent data suggest that minorities might be less likely to seek surgery. Whether minorities who seek surgery are also less likely to proceed with surgery is unclear. We interviewed 651 patients who sought bariatric surgery at two academic medical centers to examine whether ethnic minorities are less likely to proceed with surgery than Caucasians and whether minorities who do proceed with surgery have higher illness burden than their counterparts. We collected patient demographics and abstracted clinical data from the medical records. We then conducted multivariable analyses to examine the association between race and the likelihood of proceeding with bariatric surgery within 1 year of initial interview and to compare the illness burden by race and ethnicity among those who underwent surgery. Of our study sample, 66 % were Caucasian, 18 % were African-American, and 12 % were Hispanics. After adjustment for socioeconomic factors, there were no racial differences in who proceeded with bariatric surgery. Among those who proceeded with surgery, illness burden was comparable between minorities and Caucasian patients with the exception that African-Americans were underrepresented among those with reflux disease (0.4, 95 % CI 0.2-0.7) and depression (0.4, 0.2-0.7), and overrepresented among those with anemia (4.8, 2.4-9.6) than Caucasian patients. Race and ethnicity were not independently associated with likelihood of proceeding with bariatric surgery. Minorities who proceeded with surgery did not clearly have higher illness burden than Caucasian patients. C1 [Stanford, Fatima Cody] Massachusetts Gen Hosp, Gastrointestinal Unit, Obes Metab & Nutr Inst, Boston, MA 02114 USA. [Stanford, Fatima Cody] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. [Stanford, Fatima Cody; Jones, Daniel B.; Schneider, Benjamin E.; Blackburn, George L.; Wee, Christina C.] Harvard Univ, Sch Med, Boston, MA USA. [Jones, Daniel B.; Schneider, Benjamin E.; Blackburn, George L.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Minimally Invas Surg, Boston, MA 02215 USA. [Apovian, Caroline M.; Hess, Donald T.; Bourland, Ashley C.] Boston Univ, Sch Med, Dept Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Chiodi, Sarah; Robert, Shirley; Wee, Christina C.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Wee, CC (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. EM cwee@bidmc.harvard.edu OI Stanford, Fatima/0000-0003-4616-533X FU National Institutes of Health [R01DK073302]; NIH Midcareer Mentorship Award [K24DK087932] FX The study was funded by a grant from the National Institutes of Health (R01DK073302, PI Wee). Dr. Wee is also supported by a NIH Midcareer Mentorship Award (K24DK087932). The funder 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. Ms. Chiodi has full access to the data and takes responsibility for the integrity and accuracy of the data. NR 11 TC 1 Z9 1 U1 1 U2 5 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 SEP PY 2015 VL 29 IS 9 BP 2794 EP 2799 DI 10.1007/s00464-014-4014-8 PG 6 WC Surgery SC Surgery GA CP6PG UT WOS:000360009100046 PM 25492453 ER PT J AU Shim, J Park, JH Lee, JY Uhm, JS Joung, B Lee, MH Ellinoe, PT Pak, HN AF Shim, Jaemin Park, Jae Hyung Lee, Ji-Young Uhm, Jae-Sun Joung, Boyoung Lee, Moon-Hyoung Ellinoe, Patrick T. Pak, Hui-Nam TI eNOS3 Genetic Polymorphism Is Related to Post-Ablation Early Recurrence of Atrial Fibrillation SO YONSEI MEDICAL JOURNAL LA English DT Article DE Atrial fibrillation; eNOS gene; catheter ablation; recurrence ID RADIOFREQUENCY CATHETER ABLATION; EXPERT CONSENSUS STATEMENT; HEART RHYTHM ASSOCIATION; C-REACTIVE PROTEIN; NITRIC-OXIDE; SURGICAL ABLATION; AMERICAN-COLLEGE; EUROPEAN-SOCIETY; TASK-FORCE; FOLLOW-UP AB Purpose: Previous studies have demonstrated an association between eNOS polymorphisms and atrial fibrillation (AF). We sought to determine whether eNOS polymorphisms are associated with AF recurrence after a radiofrequency catheter ablation (RFCA). Materials and Methods: A total of 500 consecutive patients (56 +/- 11 years, 77% male) with paroxysmal (68%) or persistent (32%) AF who underwent RFCA and 500 age, gender-matched controls were genotyped for the eNOS3 single nucleotide polymorphism (rs1799983). AF recurrence was monitored according to 2012 ACC/AHA/ESC guidelines. Results: The frequencies of the rsI799983 variant alleles (T) in the case and control group were not significantly different (OR 1.05, 95% CI 0.75-1.46, p=0.798). AF patients with rs1799983 variants were more likely to have coronary artery disease or stroke than those without genetic variant at this gene (31.0% vs. 17.3%, p=0.004). During mean 17 months follow-up, early recurrence of AF (ERAF; within 3 months) and clinical recurrence (CR) of AF were 31.8% and 24.8%, respectively. The rsI799983 variant was associated with higher risk of ERAF (OR 1.71, 95% CI 1.06-2.79, p=0.028), but not with CR. ERAF occurred earlier (11 +/- 16 days) in variant group than those without variant allele (20 +/- 25 days, p=0.016). A multiple logistic regression analysis showed that presence of the rs1799983 variant (OR 1.75, 95% CI 1.07-2.86, p=0.026) and persistent AF were independent predictors for ERAF after AF ablation. Conclusion: The rs1799983 variant of the eNOS3 gene was associated with ERAF, but not with CR, after RFCA. eNOS3 gene variants may have a potential role for stratification of post-ablation management. C1 [Shim, Jaemin] Korea Univ, Anam Hosp, Dept Cardiol, Seoul, South Korea. [Park, Jae Hyung; Lee, Ji-Young; Uhm, Jae-Sun; Joung, Boyoung; Lee, Moon-Hyoung; Pak, Hui-Nam] Yonsei Univ Hlth Syst, Dept Cardiol, Seoul 120752, South Korea. [Park, Jae Hyung; Lee, Ji-Young; Pak, Hui-Nam] Yonsei Univ Hlth Syst, Cardiovasc Genome Ctr, Seoul, South Korea. [Ellinoe, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinoe, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Pak, HN (reprint author), Yonsei Univ Hlth Syst, Dept Cardiol, 50-1 Yonsei Ro, Seoul 120752, South Korea. EM hnpak@yuhs.ac OI Lee, Ji-Young/0000-0002-7784-1401 FU Korea Health 21 R&D Project, Ministry of Health and Welfare, and Basic Science Research Program under the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology, Republic of Korea [A085136, 7-2013-0362] FX This work was supported by a grant of the Korea Health 21 R&D Project (A085136), Ministry of Health and Welfare, and Basic Science Research Program under the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (7-2013-0362), Republic of Korea. We appreciate National Biobank of Korea (KOBB-2012-00) for kindly providing control DNA. NR 30 TC 4 Z9 4 U1 1 U2 1 PU YONSEI UNIV COLL MEDICINE PI SEOUL PA 50-1 YONSEI-RO, SEODAEMUN-GU, SEOUL 120-752, SOUTH KOREA SN 0513-5796 EI 1976-2437 J9 YONSEI MED J JI Yonsei Med. J. PD SEP 1 PY 2015 VL 56 IS 5 BP 1244 EP 1250 DI 10.3349/ymj.2015.56.5.1244 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CP4XP UT WOS:000359886200011 PM 26256966 ER PT J AU Allen, JD Tom, LS Leyva, B Rustan, S Ospino, H Negron, R Torres, MI Galeas, AV AF Allen, Jennifer D. Tom, Laura S. Leyva, Bryan Rustan, Sarah Ospino, Hosffman Negron, Rosalyn Torres, Maria Idali Galeas, Ana V. TI Recruiting and Surveying Catholic Parishes for Cancer Control Initiatives: Lessons Learned From the CRUZA Implementation Study SO HEALTH PROMOTION PRACTICE LA English DT Article DE survey administration; organizational recruitment; faith-based organizations; churches; Hispanic; Latino health; implementation research ID HISPANIC WOMEN; NATIONAL CONGREGATIONS; PREVENTION PROGRAM; EDUCATION-PROGRAM; BLACK CHURCHES; PROMOTION; ORGANIZATIONS; INTERVENTIONS; BELIEFS; PROJECT AB Background. We describe activities undertaken to conduct organizational surveys among faith-based organizations in Massachusetts as part of a larger study designed to promote parish-based cancer control programs for Latinos. Method. Catholic parishes located in Massachusetts that provided Spanish-language mass were eligible for study participation. Parishes were identified through diocesan records and online directories. Prior to parish recruitment, we implemented a variety of activities to gain support from Catholic leaders at the diocesan level. We then recruited individual parishes to complete a four-part organizational survey, which assessed (A) parish leadership, (B) financial resources, (C) involvement in Hispanic Ministry, and (D) health and social service offerings. Our goal was to administer each survey component to a parish representatives who could best provide an organizational perspective on the content of each component (e.g., A = pastors, B = business managers, C = Hispanic Ministry leaders, and D = parish nurse or health ministry leader). Here, we present descriptive statistics on recruitment and survey administration processes. Results. Seventy-five percent of eligible parishes responded to the survey and of these, 92% completed all four components. Completed four-part surveys required an average of 16.6 contact attempts. There were an average of 2.1 respondents per site. Pastoral staff were the most frequent respondents (79%), but they also required the most contact attempts (M = 9.3, range = 1-27). While most interviews were completed by phone (71%), one quarter were completed during in-person site visits. Conclusions. We achieved a high survey completion rate among organizational representatives. Our lessons learned may inform efforts to engage and survey faith-based organizations for public health efforts. C1 [Allen, Jennifer D.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Tom, Laura S.; Galeas, Ana V.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Leyva, Bryan] NCI, NIH, Bethesda, MD 20892 USA. [Rustan, Sarah; Negron, Rosalyn; Torres, Maria Idali] Univ Massachusetts, Boston, MA 02125 USA. [Ospino, Hosffman] Boston Coll, Sch Theol & Minist, Boston, MA USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_allen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU NCCDPHP CDC HHS [U48DP001946]; NCI NIH HHS [U54 CA156732, U54 CA156734, U54CA156732]; NIMHD NIH HHS [R21MD005976] NR 34 TC 2 Z9 2 U1 5 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1524-8399 EI 1552-6372 J9 HEALTH PROMOT PRACT JI Health Promot. Pract. PD SEP PY 2015 VL 16 IS 5 BP 667 EP 676 DI 10.1177/1524839915582174 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CP5LA UT WOS:000359922200006 PM 25878192 ER PT J AU Durazzo, TC Mon, A Gazdzinski, S Yeh, PH Meyerhoff, DJ AF Durazzo, Timothy C. Mon, Anderson Gazdzinski, Stefan Yeh, Ping-Hong Meyerhoff, Dieter J. TI Serial longitudinal magnetic resonance imaging data indicate non-linear regional gray matter volume recovery in abstinent alcohol-dependent individuals SO ADDICTION BIOLOGY LA English DT Article DE Alcohol use disorders; brain volume; cigarette smoking; cognition; recovery ID CHRONIC CIGARETTE-SMOKING; NATIONAL EPIDEMIOLOGIC SURVEY; USE DISORDERS; TREATMENT-SEEKING; BRAIN VOLUMES; NEUROCOGNITION; PREVALENCE; MECHANISMS; DRINKERS; RELAPSE AB The trajectory of regional volume changes during the first year of sustained abstinence in those recovering from an alcohol use disorder is unclear because previous research typically employed only two assessment points. To better understand the trajectory of regional brain volume recovery in treatment-seeking alcohol-dependent individuals (ALC), regional brain volumes were measured after 1 week, 1 month and 7.5 months of sustained abstinence via magnetic resonance imaging at 1.5T. ALC showed significant volume increases in frontal, parietal and occipital gray matter (GM) and white matter (WM), total cortical GM and total lobar WM, thalamus and cerebellum, and decreased ventricular volume over 7.5 months of abstinence. Volume increases in regional GM were significantly greater over 1 week to 1 month than from 1 month to 7.5 months of abstinence, indicating a non-linear rate of change in regional GM over 7.5 months. Overall, regional lobar WM showed linear volume increases over 7.5 months. With increasing age, smoking ALC showed lower frontal and total cortical GM volume recovery than non-smoking ALC. Despite significant volume increases, ALC showed smaller GM volumes in all regions, except the frontal cortex, than controls after 7.5 months of abstinence. ALC and controls showed no regional WM volume differences at any assessment point. In non-smoking ALC only, increasing regional GM and WM volumes were related to improving processing speed. Findings may indicate a differential rate of recovery of cell types/cellular components contributing to GM and WM volume during early abstinence, and that GM volume deficits persist after 7.5 months of sustained sobriety in this ALC cohort. C1 [Durazzo, Timothy C.; Mon, Anderson; Gazdzinski, Stefan; Yeh, Ping-Hong; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Mon, Anderson; Gazdzinski, Stefan; Yeh, Ping-Hong; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU National Institutes of Health [DA24136, AA10788] FX This work was supported by grants from the National Institutes of Health (DA24136 to T.C.D and AA10788 to D.J.M.) administered by the Northern California Institute for Research and Education, and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. We thank Mary Rebecca Young, Bill Clift, Ricky Chen, and Drs. Ellen Herbst, Peter Banys and Steven Batki of the San Francisco VA Medical Center Substance Abuse Day Hospital, and Dr. David Pating, Karen Moise and their colleagues at the Kaiser Permanente Chemical Dependency Recovery Program in San Francisco for their valuable assistance in participant recruitment. We also thank Mary Vertinski and Molly Estrin for their assistance in the neurocognitive and clinical assessment of participants. Finally, we thank the study participants who made this research possible. NR 48 TC 6 Z9 6 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD SEP PY 2015 VL 20 IS 5 BP 956 EP 967 DI 10.1111/adb.12180 PG 12 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA CP1XF UT WOS:000359670200009 PM 25170881 ER PT J AU Dean, LT Subramanian, SV Williams, DR Armstrong, K Charles, CZ Kawachi, I AF Dean, Lorraine T. Subramanian, S. V. Williams, David R. Armstrong, Katrina Charles, Camille Zubrinsky Kawachi, Ichiro TI Getting Black Men to Undergo Prostate Cancer Screening: The Role of Social Capital SO AMERICAN JOURNAL OF MENS HEALTH LA English DT Article DE prostate cancer; screening; prostate-specific antigen (PSA); Black/African American men; social capital; community participation; Philadelphia ID AFRICAN-AMERICAN MEN; BREAST-CANCER; HEALTH; ASSOCIATION; GUIDELINE; BARRIERS; SOCIETY AB Despite higher rates of prostate cancer-related mortality and later stage of prostate cancer diagnosis, Black/African American men are significantly less likely than non-Hispanic White men to use early detection screening tools, like prostate-specific antigen (PSA) testing for prostate cancer. Lower screening rates may be due, in part, to controversy over the value of prostate cancer screenings as part of routine preventive care for men, but Black men represent a high-risk group for prostate cancer that may still benefit from PSA testing. Exploring the role of social factors that might be associated with PSA testing can increase knowledge of what might promote screening behaviors for prostate cancer and other health conditions for which Black men are at high risk. Using multilevel logistic regression, this study analyzed self-report lifetime use of PSA test for 829 Black men older than 45 years across 381 Philadelphia census tracts. This study included individual demographic and aggregated social capital data from the Public Health Management Corporation's 2004, 2006, and 2008 waves of the Community Health Database, and sociodemographic characteristics from the 2000 U.S. Census. Each unit increase in community participation was associated with a 3 to 3.5 times greater likelihood of having had a PSA test (odds ratio = 3.35). Findings suggest that structural forms of social capital may play a role in screening behaviors for Black men in Philadelphia. A better understanding of the mechanism underlying the link between social capital and screening behaviors can inform how researchers and interventionists develop tools to promote screening for those who need it. C1 [Dean, Lorraine T.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Subramanian, S. V.; Williams, David R.; Kawachi, Ichiro] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Armstrong, Katrina] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Charles, Camille Zubrinsky] Univ Penn, Sch Arts & Sci, Philadelphia, PA 19104 USA. RP Dean, LT (reprint author), Univ Penn, Dept Biostat & Epidemiol, 9th Floor Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM ldean@post.harvard.edu FU National Institutes of Health and National Cancer Institute [1F31CA136236)] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institutes of Health and National Cancer Institute (Grant No. 1F31CA136236). NR 51 TC 5 Z9 5 U1 7 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1557-9883 EI 1557-9891 J9 AM J MENS HEALTH JI Am. J. Mens Health PD SEP PY 2015 VL 9 IS 5 BP 385 EP 396 DI 10.1177/1557988314546491 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CP2RT UT WOS:000359725500006 PM 25117538 ER PT J AU Amini, N Kim, Y Hyder, O Spolverato, G Wu, CL Page, AJ Pawlik, TM AF Amini, Neda Kim, Yuhree Hyder, Omar Spolverato, Gaya Wu, Christopher L. Page, Andrew J. Pawlik, Timothy M. TI A nationwide analysis of the use and outcomes of perioperative epidural analgesia in patients undergoing hepatic and pancreatic surgery SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Epidural analgesia; Liver resection; Pancreatic resection; Outcome ID COMPLICATIONS FOLLOWING PANCREATICODUODENECTOMY; LIVER RESECTION; COLORECTAL SURGERY; ENHANCED RECOVERY; POSTOPERATIVE PAIN; RANDOMIZED TRIAL; ANESTHESIA; METAANALYSIS; MORBIDITY; CARE AB BACKGROUND: We sought to define trends in the use of epidural analgesia (EA) for hepatopancreatic procedures, as well as to characterize inpatient outcomes relative to the use of EA. METHODS: The Nationwide Inpatient Sample database was queried to identify all elective hepatopancreatic surgeries between 2000 and 2012. In-hospital outcomes were compared among patients receiving EA vs conventional analgesia using propensity matching. RESULTS: EA utilization was 7.4% (n = 3,961). The use of EA among minimally invasive procedures increased from 3.8% in 2000 to 9.1% in 2012. The odds of sepsis (odds ratio [OR] .72, 95% confidence interval [CI] .56 to .93), respiratory failure (OR .79, 95% CI .69 to .91), and postoperative pneumonia (OR .77, 95% CI .61 to .98), as well as overall in-hospital mortality (OR .72, 95% CI .56 to .93) were lower in the EA cohort (all P <.05). In contrast, no association was noted between EA and postoperative hemorrhage (OR .81, 95% CI .65 to 1.01, P = .06). CONCLUSIONS: EA use among patients undergoing hepatopancreatic procedures remains low. After controlling for confounding factors, EA remained associated with a reduction in specific pulmonary-related complications, as well as in-hospital mortality. (C) 2015 Elsevier Inc. All rights reserved. C1 [Amini, Neda; Kim, Yuhree; Spolverato, Gaya; Page, Andrew J.; Pawlik, Timothy M.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21287 USA. [Hyder, Omar] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Management, Boston, MA 02114 USA. [Wu, Christopher L.] Johns Hopkins Univ Hosp, Dept Anesthesia & Crit Care Med, Baltimore, MD 21287 USA. RP Pawlik, TM (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, 600 North Wolfe St,Blalock 688, Baltimore, MD 21287 USA. EM tpawlik1@jhmi.edu FU NCI NIH HHS [P30 CA006973] NR 35 TC 2 Z9 2 U1 0 U2 8 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD SEP PY 2015 VL 210 IS 3 BP 483 EP 491 DI 10.1016/j.amjsurg.2015.04.009 PG 9 WC Surgery SC Surgery GA CP0WN UT WOS:000359597500012 PM 26105799 ER PT J AU Baldini, EH Bosch, W Kane, JM Abrams, RA Salerno, KE Deville, C Raut, CP Petersen, IA Chen, YL Mullen, JT Millikan, KW Karakousis, G Kendrick, ML DeLaney, TF Wang, D AF Baldini, Elizabeth H. Bosch, Walter Kane, John M., III Abrams, Ross A. Salerno, Kilian E. Deville, Curtiland Raut, Chandrajit P. Petersen, Ivy A. Chen, Yen-Lin Mullen, John T. Millikan, Keith W. Karakousis, Giorgos Kendrick, Michael L. DeLaney, Thomas F. Wang, Dian TI Retroperitoneal Sarcoma (RPS) High Risk Gross Tumor Volume Boost (HR GTV Boost) Contour Delineation Agreement Among NRG Sarcoma Radiation and Surgical Oncologists SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SOFT-TISSUE SARCOMAS; PROGNOSTIC-FACTORS; LOCAL RECURRENCE; POSITIVE MARGINS; SURGERY; THERAPY; RADIOTHERAPY; RESECTION; SURVIVAL; EXTREMITIES AB Curative intent management of retroperitoneal sarcoma (RPS) requires gross total resection. Preoperative radiotherapy (RT) often is used as an adjuvant to surgery, but recurrence rates remain high. To enhance RT efficacy with acceptable tolerance, there is interest in delivering "boost doses" of RT to high-risk areas of gross tumor volume (HR GTV) judged to be at risk for positive resection margins. We sought to evaluate variability in HR GTV boost target volume delineation among collaborating sarcoma radiation and surgical oncologist teams. Radiation planning CT scans for three cases of RPS were distributed to seven paired radiation and surgical oncologist teams at six institutions. Teams contoured HR GTV boost volumes for each case. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. HRGTV boost volume contour agreement between the seven teams was "substantial" or "moderate" for all cases. Agreement was best on the torso wall posteriorly (abutting posterior chest abdominal wall) and medially (abutting ipsilateral para-vertebral space and great vessels). Contours varied more significantly abutting visceral organs due to differing surgical opinions regarding planned partial organ resection. Agreement of RPS HRGTV boost volumes between sarcoma radiation and surgical oncologist teams was substantial to moderate. Differences were most striking in regions abutting visceral organs, highlighting the importance of collaboration between the radiation and surgical oncologist for "individualized" target delineation on the basis of areas deemed at risk and planned resection. C1 [Baldini, Elizabeth H.] Brigham & Womens Hosp L2, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Bosch, Walter] Washington Univ, Dept Radiat Oncol, St Louis, MO USA. [Kane, John M., III] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Abrams, Ross A.; Wang, Dian] Rush Univ, Med Ctr, Dept Radiat Oncol, Chicago, IL 60612 USA. [Salerno, Kilian E.] Roswell Pk Canc Inst, Dept Radiat Oncol, Buffalo, NY 14263 USA. [Deville, Curtiland] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Raut, Chandrajit P.] Dana Farber Brigham & Womens Canc Ctr, Dept Surg, Boston, MA USA. [Petersen, Ivy A.] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. [Chen, Yen-Lin; DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Millikan, Keith W.] Rush Univ, Med Ctr, Dept Surg, Chicago, IL 60612 USA. [Karakousis, Giorgos] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Kendrick, Michael L.] Mayo Clin, Dept Surg, Rochester, MN USA. RP Baldini, EH (reprint author), Brigham & Womens Hosp L2, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. EM ebaldini@partners.org RI Deville, Curtiland/B-2819-2013 OI Deville, Curtiland/0000-0003-4846-6486 FU National Cancer Institute [U10CA21661, U10CA180868, U10CA180822, U10CA37422, U24CA180803, U24CA81647] FX Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, U24CA180803, and U24CA81647 from the National Cancer Institute. NR 34 TC 1 Z9 1 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 SEP PY 2015 VL 22 IS 9 BP 2846 EP 2852 DI 10.1245/s10434-015-4633-x PG 7 WC Oncology; Surgery SC Oncology; Surgery GA CO8NA UT WOS:000359425000009 PM 26018727 ER PT J AU Zorbas, KA Economopoulos, KP Vlahos, NF AF Zorbas, Konstantinos A. Economopoulos, Konstantinos P. Vlahos, Nikos F. TI Continuous versus cyclic oral contraceptives for endometriosis: any conclusive evidence? Reply SO ARCHIVES OF GYNECOLOGY AND OBSTETRICS LA English DT Letter C1 [Zorbas, Konstantinos A.] Gen Hosp Veria, Dept Obstet & Gynecol, Veria, Greece. [Zorbas, Konstantinos A.; Economopoulos, Konstantinos P.] Soc Jr Doctors, Athens, Greece. [Economopoulos, Konstantinos P.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Boston, MA 02114 USA. [Vlahos, Nikos F.] Univ Athens, Sch Med, Aretaieion Hosp, Dept Obstet & Gynecol 2, GR-11527 Athens, Greece. RP Economopoulos, KP (reprint author), Soc Jr Doctors, Athens, Greece. EM keconomopoulos@mgh.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0932-0067 EI 1432-0711 J9 ARCH GYNECOL OBSTET JI Arch. Gynecol. Obstet. PD SEP PY 2015 VL 292 IS 3 BP 479 EP 480 DI 10.1007/s00404-015-3780-4 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CO7YO UT WOS:000359380100004 PM 26048262 ER PT J AU Zorbas, KA Economopoulos, KP Vlahos, NF AF Zorbas, Konstantinos A. Economopoulos, Konstantinos P. Vlahos, Nikos F. TI Reply to: Continuous or cyclic contraceptives for endometriosis: a question still without an answer SO ARCHIVES OF GYNECOLOGY AND OBSTETRICS LA English DT Letter ID ORAL-CONTRACEPTIVES C1 [Zorbas, Konstantinos A.] Gen Hosp Veria, Dept Obstet & Gynecol, Veria, Greece. [Zorbas, Konstantinos A.; Economopoulos, Konstantinos P.] Soc Jr Doctors, Athens, Greece. [Economopoulos, Konstantinos P.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Boston, MA 02114 USA. [Vlahos, Nikos F.] Univ Athens, Sch Med, Aretaieion Hosp, Dept Obstet & Gynecol 2, GR-11527 Athens, Greece. RP Economopoulos, KP (reprint author), Soc Jr Doctors, Athens, Greece. EM keconomopoulos@mgh.harvard.edu OI Economopoulos, Konstantinos/0000-0003-4856-0405 NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0932-0067 EI 1432-0711 J9 ARCH GYNECOL OBSTET JI Arch. Gynecol. Obstet. PD SEP PY 2015 VL 292 IS 3 BP 483 EP 484 DI 10.1007/s00404-015-3781-3 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CO7YO UT WOS:000359380100006 PM 26054826 ER PT J AU Lin, H Fang, HY Wang, J Meng, QH Dai, XD Wu, SR Luo, J Pu, D Chen, LB Minick, D Arai, K Mandeville, ET Lo, E Holder, JC Chuang, TT Zhao, J AF Lin, Hong Fang, Haiyan Wang, Jamie Meng, Qinghua Dai, Xuedong Wu, Sharon Luo, Jie Pu, Dan Chen, Libo Minick, Douglas Arai, Ken Mandeville, Emiri T. Lo, Eng Holder, Julie C. Chuang, Tsu Tshen Zhao, Jing TI Discovery of a novel 2,3,11,11a-tetrahydro-1H-pyrazino[1,2-b]isoquinoline-1,4(6H)-dione series promoting neurogenesis of human neural progenitor cells SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Neurogenesis; Neural progenitor cell; Structure-activity relationship ID HIPPOCAMPAL NEUROGENESIS; ALZHEIMERS-DISEASE; DRUG DISCOVERY; STRATEGIES; MEMORY; BRAIN; TOOL AB A novel neurogenic compound (1), discovered from a mouse neural progenitor cell (NPC) screen, showed profound neurogenic effect on human NPCs. Synthesis and SAR of this novel 2,3,11,11a-tetrahydro-1H-pyrazino[ 1,2-b]isoquinoline-1,4(6H)-dione series are described. Compound 20 is brain penetrable in rodents, and promotes neurogenesis in wild type mice, therefore it is a good tool molecule to study neurogenesis induction as a potential treatment for conditions associated with neurogenesis impairment diseases. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Lin, Hong] GlaxoSmithKline, Regenerat Med Discovery Performance Unit, Collegeville, PA 19426 USA. [Fang, Haiyan; Wang, Jamie; Meng, Qinghua; Dai, Xuedong; Wu, Sharon; Luo, Jie; Zhao, Jing] GlaxoSmithKline, Regenerat Med Discovery Performance Unit, Pudong 201203, Shanghai, Peoples R China. [Pu, Dan; Chen, Libo] GlaxoSmithKline, Platform Technol & Sci, Pudong 201203, Shanghai, Peoples R China. [Minick, Douglas] GlaxoSmithKline, Platform Technol & Sci, Res Triangle Pk, NC 27709 USA. [Arai, Ken; Mandeville, Emiri T.; Lo, Eng] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Charlestown, MA 02129 USA. [Holder, Julie C.; Chuang, Tsu Tshen] GlaxoSmithKline, Regenerat Med Discovery Performance Unit, Stevenage SG1 2NY, Herts, England. RP Lin, H (reprint author), GlaxoSmithKline, Regenerat Med Discovery Performance Unit, 1250 South Collegeville Rd, Collegeville, PA 19426 USA. EM hong.2.lin@gsk.com NR 21 TC 2 Z9 2 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD SEP 1 PY 2015 VL 25 IS 17 BP 3748 EP 3753 DI 10.1016/j.bmcl.2015.05.084 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA CN9XD UT WOS:000358802900065 PM 26142946 ER PT J AU Witzig, TE Hong, F Micallef, IN Gascoyne, RD Dogan, A Wagner, H Kahl, BS Advani, RH Horning, SJ AF Witzig, Thomas E. Hong, Fangxin Micallef, Ivana N. Gascoyne, Randy D. Dogan, Ahmet Wagner, Henry, Jr. Kahl, Brad S. Advani, Ranjana H. Horning, Sandra J. TI A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402 SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE radioimmunotherapy; large cell lymphoma; R-CHOP ID ONCOLOGY-GROUP; PLUS RADIOTHERAPY; RESPONSE CRITERIA; R-CHOP; CHEMOTHERAPY; RITUXIMAB; CLASSIFICATION; PROGNOSIS; SURVIVAL AB Patients with early stage diffuse large B-cell lymphoma (DLBCL) receive RCHOP (rituximab cyclophosphamide, doxorubicin, vincristine, prednisone) alone or with involved field radiotherapy (IFRT). Anti-CD20 radioimmunotherapy (RIT) delivers radiation to microscopic sites outside of known disease. This phase II study aimed to achieve a functional complete response (CR) rate of 75% to RCHOP and (90)Yttrium-ibritumomab tiuxetan RIT. Patients with stages I/II DLBCL received 4-6 cycles of RCHOP followed by RIT [148MBq/kg (04mCi/kg)]; patients with positron emission tomographypositive sites of disease after RCHOP/RIT received 30Gy IFRT. Of the 62 patients enrolled; 53 were eligible. 42% (22/53) had stage I/IE; 58% (31/53) stage II/IIE. After RCHOP, 79% (42/53) were in CR/unconfirmed CR. Forty-eight patients proceeded to RIT. One partial responder after RIT received IFRT and achieved a CR. The best response after RCHOP+RIT in all 53 patients was a functional CR rate of 89% (47/53; 95% confidence interval: 77-96%). With a median follow-up of 59years, 7 (13%) patients have progressed and 4 (8%) have died (2 with DLBCL). At 5years, 78% of patients remain in remission and 94% are alive. Chemoimmunotherapy and RIT is an active regimen for early stage DLBCL patients. Eighty-nine percent of patients achieved functional CR without the requirement of IFRT. This regimen is worthy of further study for early stage DLBCL in a phase III trial. C1 [Witzig, Thomas E.; Micallef, Ivana N.; Dogan, Ahmet] Mayo Clin, Rochester, MN 55905 USA. [Hong, Fangxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. [Wagner, Henry, Jr.] Penn State Canc Inst, Hershey, PA USA. [Kahl, Brad S.] Univ Wisconsin, Madison, WI USA. [Advani, Ranjana H.; Horning, Sandra J.] Stanford Univ, Stanford, CA 94305 USA. RP Witzig, TE (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. EM Witzig.thomas@mayo.edu FU Public Health Service Grants [CA21115, CA23318, CA66636, CA13650, CA21076]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was conducted by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA21115, CA23318, CA66636, CA13650, CA21076 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Biospecimens were provided by the ECOG Pathology Coordinating Office and Reference Laboratory. NR 25 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2015 VL 170 IS 5 BP 679 EP 686 DI 10.1111/bjh.13493 PG 8 WC Hematology SC Hematology GA CP0ZU UT WOS:000359606400008 PM 25974212 ER PT J AU Davids, MS Vartanov, A Werner, L Neuberg, D Dal Cin, P Brown, JR AF Davids, Matthew S. Vartanov, Alexander Werner, Lillian Neuberg, Donna Dal Cin, Paola Brown, Jennifer R. TI Controversial fluorescence insitu hybridization cytogenetic abnormalities in chronic lymphocytic leukaemia: new insights from a large cohort SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; prognostic factors; IgH; fluorescence insitu hybridization; cytogenetics of leukaemia ID NEWLY-DIAGNOSED PATIENTS; CLL RESEARCH CONSORTIUM; GENOMIC ABERRATIONS; PROGNOSIS; SURVIVAL; DELETION; LOSSES; NUMBER; CELLS AB The significance of rarer cytogenetic abnormalities in chronic lymphocytic leukaemia (CLL) remains controversial. We performed fluorescence insitu hybridization (FISH) prior to initial therapy on 618 CLL patients seen at our centre between 2005 and 2012. With a median follow-up of 56years, we found that 55 patients harbouring 14q32 rearrangements without t(14;18) had a shorter time to first treatment (TTFT) (median 26months, P=003) than patients with t(14;18) (median not reached). Patients with mono- or bi-allelic del(13q) as a sole abnormality had a similarly long TTFT (median not reached). Those patients who harboured 3 or more FISH abnormalities without del(17p) had a short TTFT (46months), comparable to patients with del(17p) (8months); however, the overall survival for patients with 3 or more FISH abnormalities was longer than for patients with del(17p) with 0 or 1 additional abnormalities (median not reached vs. 54months). FISH cytogenetics remains a useful genetic tool in the clinic, even in the era of next generation sequencing and, as such, our data provide valuable new insights for counselling patients. C1 [Davids, Matthew S.; Vartanov, Alexander; Brown, Jennifer R.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA USA. [Werner, Lillian; Neuberg, Donna] Brigham & Womens Hosp, Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dal Cin, Paola] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Davids, MS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM matthew_davids@dfci.harvard.edu FU American Society of Clinical Oncology Career Development Award; National Institutes of Health LRP Award; Leukemia and Lymphoma Society FX The authors wish to thank Laura Rassenti and the CLL Research Consortium for performing IGHV and ZAP70 assays. MSD was a Leukemia & Lymphoma Society Special Fellow in Clinical Research, currently holds an American Society of Clinical Oncology Career Development Award, and is a recipient of a National Institutes of Health LRP Award. JRB was a Scholar of the American Society of Hematology and a Scholar in Clinical Research also with support from a Translational Research Program grant from the Leukemia and Lymphoma Society. NR 26 TC 4 Z9 4 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2015 VL 170 IS 5 BP 694 EP 703 DI 10.1111/bjh.13498 PG 10 WC Hematology SC Hematology GA CP0ZU UT WOS:000359606400010 PM 26032737 ER PT J AU Jayewickreme, CD Shivdasani, RA AF Jayewickreme, Chenura D. Shivdasani, Ramesh A. TI Control of stomach smooth muscle development and intestinal rotation by transcription factor BARX1 SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Digestive tract development; Enteric muscle differentiation; Gut patterning; Homeotic genes ID SITUS-SPECIFIC MORPHOGENESIS; GUT; CELLS; PITX2; DIFFERENTIATION; INHIBITION; EXPRESSION; MYOGENESIS; SIGNALS; GROWTH AB Diverse functions of the homeodomain transcription factor BARX1 include Wnt-dependent, non-cell autonomous specification of the stomach epithelium, tracheo-bronchial septation, and Wnt-independent expansion of the spleen primordium. Tight spatio-temporal regulation of Barx1 levels in the mesentery and stomach mesenchyme suggests additional roles. To determine these functions, we forced constitutive BARX1 expression in the Bapx1 expression domain, which includes the mesentery and intestinal mesenchyme, and also examined Barx1(-/-) embryos in further detail. Transgenic embryos invariably showed intestinal truncation and malrotation, in part reflecting abnormal left-right patterning. Ectopic BARX1 expression did not affect intestinal epithelium, but intestinal smooth muscle developed with features typical of the stomach wall. BARX1, which is normally restricted to the developing stomach, drives robust smooth muscle expansion in this organ by promoting proliferation of myogenic progenitors at the expense of other sub-epithelial cells. Undifferentiated embryonic stomach and intestinal mesenchyme showed modest differences in mRNA expression and BARX1 was sufficient to induce much of the stomach profile in intestinal cells. However, limited binding at cis-regulatory sites implies that BARX1 may act principally through other transcription factors. Genes expressed ectopically in BARX1(+) intestinal mesenchyme and reduced in Barx1(-/-) stomach mesenchyme include Isl1, Pitx1, Six2 and Pibc2, transcription factors known to control left-right patterning and influence smooth muscle development. The sum of evidence suggests that potent BARX1 functions in intestinal rotation and stomach myogenesis occur through this small group of intermediary transcription factors. (C) 2015 Elsevier Inc. All rights reserved. C1 [Jayewickreme, Chenura D.; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ramesh_shivdasani@dfci.harvard.edu OI Jayewickreme, Chenura/0000-0003-1689-6035 FU National Institutes of Heath [R01DK081113] FX Supported in part by National Institutes of Heath Grant R01DK081113. We thank Byeong-Moo Kim, Janghee Woo and Justina Chen for crucial efforts in early phases of the work; Isabelle Miletich and Paul Sharpe for Barx1 knockout mice and in situ hybridization; Warren Zimmer for the gift of Bapx1Cre mice; William Hahn for providing a p53DD plasmid; Christopher Wright for PDX1 antiserum; and Unmesh Jadhav, Kazu Murata, Maddie Saxena and Adrianna San Roman for helping complete experiments during manuscript revision. NR 33 TC 2 Z9 2 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 2015 VL 405 IS 1 BP 21 EP 32 DI 10.1016/j.ydbio.2015.05.024 PG 12 WC Developmental Biology SC Developmental Biology GA CO9OA UT WOS:000359503900003 PM 26057579 ER PT J AU Jackson, JW VanderWeele, TJ Blacker, D Schneeweiss, S AF Jackson, John W. VanderWeele, Tyler J. Blacker, Deborah Schneeweiss, Sebastian TI Mediators of First-Versus Second-generation Antipsychotic-related Mortality in Older Adults SO EPIDEMIOLOGY LA English DT Article ID CEREBROVASCULAR EVENTS; ADMINISTRATIVE DATA; PREDICTIVE-VALUE; VENTRICULAR-ARRHYTHMIAS; SENSITIVITY-ANALYSIS; BINARY MEDIATOR; CLAIMS DATA; RISK; MEDICATIONS; DEMENTIA C1 [Jackson, John W.; Schneeweiss, Sebastian] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol, Boston, MA 02115 USA. [Jackson, John W.; Blacker, Deborah; Schneeweiss, Sebastian] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Jackson, John W.; VanderWeele, Tyler J.; Blacker, Deborah; Schneeweiss, Sebastian] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Blacker, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Boston, MA 02114 USA. RP Jackson, JW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM john.jackson@mail.harvard.edu RI Schneeweiss, Sebastian/C-2125-2013 FU NIMH [T32 MH017119]; Horace W. Goldsmith Fellowship at Harvard University; NIH [R01 ES 017876]; Alzheimer's Association; Pfizer; Novartis; Boehringer Ingelheim FX JWJ was supported by a NIMH Training Grant in Training in Psychiatric Genetics and Translational Research (T32 MH017119) and the Horace W. Goldsmith Fellowship at Harvard University; TJV was supported by a NIH Grant (R01 ES 017876); DB was supported by a grant from the Alzheimer's Association; SS is the primary investigator of unrestricted research grants from Pfizer, Novartis, and Boehringer Ingelheim. None of these funding sources had any bearing on the conception, design, conduct, reporting, or interpretation of this study. NR 40 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2015 VL 26 IS 5 BP 700 EP 709 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CP2SG UT WOS:000359726800012 PM 26035686 ER PT J AU Boutin, RD White, LM Laor, T Spitz, DJ Lopez-Ben, RR Stevens, KJ Bredella, MA AF Boutin, Robert D. White, Lawrence M. Laor, Tal Spitz, Damon J. Lopez-Ben, Robert R. Stevens, Kathryn J. Bredella, Miriam A. TI MRI findings of serous atrophy of bone marrow and associated complications SO EUROPEAN RADIOLOGY LA English DT Article DE Serous atrophy of bone marrow; Gelatinous transformation of bone marrow; Stress fracture; MRI; Cachexia ID ANOREXIA-NERVOSA; GELATINOUS TRANSFORMATION; HEMATOLOGICAL-CHANGES; SIGNAL ALTERATION; FAT; APPEARANCES; EXTREMITIES; DENSITY; DISEASE AB Objectives To report the MRI appearance of serous atrophy of bone marrow (SABM) and analyse clinical findings and complications of SABM. Methods A retrospective search of MRI examinations of SABM was performed. Symptoms, underlying conditions, MRI findings, delay in diagnosis and associated complications were recorded. Results We identified 30 patients (15 male, 15 female; mean age: 46 +/- 21 years) with MRI findings of SABM. Underlying conditions included anorexia nervosa (n=10), cachexia from malignant (n=5) and non-malignant (n=7) causes, massive weight loss after bariatric surgery (n=1), biliary atresia (n=1), AIDS (n=3), endocrine disorders (n=2) and scurvy (n=1). MRI showed mildly hypointense signal on T1-weighted and hyperintense signal on fat-suppressed fluid-sensitive images of affected bone marrow in all cases and similar signal abnormalities of the adjacent subcutaneous fat in 29/30 cases. Seven patients underwent repeat MRI due to initial misinterpretation of bone marrow signal as technical error. Superimposed fractures of the hips and lower extremities were common (n=14). Conclusions SABM occurs most commonly in anorexia nervosa and cachexia. MRI findings of SABM are often misinterpreted as technical error requiring unnecessary repeat imaging. SABM is frequently associated with fractures of the lower extremities. C1 [Boutin, Robert D.] Univ Calif Davis, Dept Radiol, Sacramento, CA 95817 USA. [White, Lawrence M.] Univ Toronto, Toronto Gen Hosp, Joint Dept Med Imaging, Toronto, ON M5G 2N2, Canada. [Laor, Tal] Cincinnati Childrens Hosp Med Ctr, Dept Radiol, Cincinnati, OH 45229 USA. [Spitz, Damon J.] New England Baptist Hosp, Dept Radiol, Boston, MA 02120 USA. [Lopez-Ben, Robert R.] Carolinas HealthCare Syst, Diagnost Radiol, Charlotte Radiol, Charlotte, NC 28211 USA. [Stevens, Kathryn J.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Bredella, Miriam A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM mbredella@partners.org NR 35 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 EI 1432-1084 J9 EUR RADIOL JI Eur. Radiol. PD SEP PY 2015 VL 25 IS 9 BP 2771 EP 2778 DI 10.1007/s00330-015-3692-5 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CO8DZ UT WOS:000359396700031 PM 25773942 ER PT J AU Verduzco, D Flaherty, KT Smalley, KSM AF Verduzco, Daniel Flaherty, Keith T. Smalley, Keiran S. M. TI Feeling energetic? New strategies to prevent metabolic reprogramming in melanoma SO EXPERIMENTAL DERMATOLOGY LA English DT Editorial Material DE BRAF; melanoma; oxidative phosphorylation; resistance ID INHIBITION C1 [Verduzco, Daniel; Smalley, Keiran S. M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Tumor Biol, Tampa, FL 33612 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Smalley, Keiran S. M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL 33612 USA. RP Smalley, KSM (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Tumor Biol, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM keiran.smalley@moffitt.org FU NCI NIH HHS [P30 CA076292, P30-CA076292, P50 CA168536, R01 CA161107] NR 8 TC 1 Z9 1 U1 0 U2 1 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 SEP PY 2015 VL 24 IS 9 BP 657 EP 658 DI 10.1111/exd.12763 PG 2 WC Dermatology SC Dermatology GA CP3LR UT WOS:000359781100005 PM 26010519 ER PT J AU Childers, RE Williams, JL Sonnenberg, A AF Childers, Ryan E. Williams, J. Lucas Sonnenberg, Amnon TI Practice patterns of sedation for colonoscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID UPPER GASTROINTESTINAL ENDOSCOPY; COLORECTAL-CANCER; UNITED-STATES; RACIAL/ETHNIC DISPARITIES; MEDICARE BENEFICIARIES; CONSCIOUS SEDATION; RACIAL-DIFFERENCES; DIAGNOSTIC YIELD; AFRICAN-AMERICAN; WEB SURVEY AB Background: Sedative and analgesic medications have been used routinely for decades to provide patient comfort, reduce procedure time, and improve examination quality during colonoscopy. Objective: To evaluate trends of sedation during colonoscopy in the United States. Setting: Endoscopic data repository of U.S. gastroenterology practices (Clinical Outcomes Research Initiative, CORI database from 2000 until 2013). Patients: The study population was made up of patients undergoing a total of 1,385,436 colonoscopies. Interventions: Colonoscopy without any intervention or with mucosal biopsy, polypectomy, various means of hemostasis, luminal dilation, stent placement, or ablation. Main Outcome Measurements: Dose of midazolam, diazepam, fentanyl, meperidine, diphenhydramine, promethazine, and propofol used for sedation during colonoscopy. Results: During the past 14 years, midazolam, fentanyl, and propofol have become the most commonly used sedatives for colonoscopy. Except for benzodiazepines, which were dosed higher in women than men, equal doses of sedation were given to female and male patients. White patients were given higher doses than other ethnic groups undergoing sedation for colonoscopy. Except for histamine-1 receptor antagonists, all sedative medications were given at lower doses to patients with increasing age. The dose of sedatives was higher in colonoscopies associated with procedural interventions or of long duration. Limitations: Potential for incomplete or incorrect documentation in the database. Conclusion: The findings reflect on colonoscopy practice in the United States during the last 14 years and provide an incentive for future research on how sex and ethnicity influence sedation practices. C1 Portland VA Med Ctr, Div Gastroenterol & Hepatol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Gastroenterol, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. FU NIDDK [UO1 CA 89389-01, U01 DK057132, R33-DK61778-01] FX This project was supported with funding from NIDDK UO1 CA 89389-01, NIDDK U01 DK057132, and R33-DK61778-01. In addition, the practice network (Clinical Outcomes Research Initiative) has received support from the following entities to support the infrastructure of the practice-based network: AstraZeneca, Novartis, Bard International, Pentax USA, ProVation, Endosoft, GIVEN Imaging, and Ethicon. All authors disclosed no financial relationships relevant to this article. NR 52 TC 1 Z9 1 U1 2 U2 6 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 SEP PY 2015 VL 82 IS 3 BP 503 EP 511 DI 10.1016/j.gie.2015.01.041 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP0XX UT WOS:000359601300013 PM 25851159 ER PT J AU Shergill, AK Conners, EE McQuaid, KR Epstein, S Ryan, JC Shah, JN Inadomi, J Somsouk, M AF Shergill, Amandeep K. Conners, Erin E. McQuaid, Kenneth R. Epstein, Sara Ryan, James C. Shah, Janak N. Inadomi, John Somsouk, Ma TI Protective association of colonoscopy against proximal and distal colon cancer and patterns in interval cancer SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLORECTAL-CANCER; SCREENING SIGMOIDOSCOPY; LOWER ENDOSCOPY; MORTALITY; POLYP; RISK; PREVENTION; VETERANS; DEATH; SURVEILLANCE AB Background: The protective effect of colonoscopy against proximal colorectal cancer is variable and depends on the detection and complete removal of precancerous polyps. Objective: To estimate the efficacy of colonoscopy in a medical center with open-access screening colonoscopy since 1998. Design: Nested case-control study with incidence density sampling. Setting: University-affiliated Veterans Affairs Medical Center. Patients: Colorectal cancer (CRC) cases and control subjects selected from screening age patients matched by age, gender, and date of first primary care visit. Main Outcome Measurement: Colonoscopy preceding the CRC diagnosis date. Results: A total of 20.2% of CRC cases had a colonoscopy in the preceding 10 years compared with 49.0% of control subjects (adjusted odds ratio [aOR], 0.20; 95% confidence interval [CI], 0.11-0.34). Colonoscopy was strongly associated with decreased odds of both distal CRC (aOR, 0.16; 95% CI, 0.07-0.34) and proximal CRC (aOR, 0.26; 95% CI, 0.11-0.58). The fraction of cases attributed to interval cancers was 10.5%. Missed lesions predominantly localized to the cecum and rectum, and recurrent lesions clustered in the hepatic flexure. Cecal intubation rate was 93% (98% in adequately prepped patients), and the adenoma detection rate was 45.2% in the control group. Limitations: Single-center, retrospective case-control design. Conclusion: In an open access colonoscopy program characterized by a high cecal intubation rate and adenoma detection rate, colonoscopy was strongly associated with reduced odds of both distal and proximal CRC. Among interval cancers, missed lesions clustered in the cecum and rectum and recurrent lesions in the hepatic flexure. C1 [Shergill, Amandeep K.; Conners, Erin E.; McQuaid, Kenneth R.; Ryan, James C.; Shah, Janak N.] San Francisco VA Med Ctr, Div Gastroenterol, Dept Med, San Francisco, CA USA. [Shergill, Amandeep K.; Conners, Erin E.; McQuaid, Kenneth R.; Ryan, James C.; Shah, Janak N.; Somsouk, Ma] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Conners, Erin E.] Univ Calif San Diego, Joint Doctoral Program Publ Hlth, San Diego, CA 92103 USA. [Conners, Erin E.] San Diego State Univ, San Diego, CA 92182 USA. [Epstein, Sara] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Inadomi, John] Univ Washington, Dept Med, Div Gastroenterol & Hepatol, Seattle, WA USA. [Somsouk, Ma] San Francisco Gen Hosp, Dept Med, Div Gastroenterol, San Francisco, CA 94110 USA. RP Shergill, AK (reprint author), 4150 Clement St, San Francisco, CA 94121 USA. FU National Institutes of Health [K23 CA157929] FX The following author received research support for this study from the National Institutes of Health (K23 CA157929): M. Somsouk. All authors disclosed no financial relationships relevant to this publication. NR 46 TC 6 Z9 6 U1 0 U2 1 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 SEP PY 2015 VL 82 IS 3 BP 529 EP + DI 10.1016/j.gie.2015.01.053 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP0XX UT WOS:000359601300017 PM 25936449 ER PT J AU Richmon, JD Yarlagadda, BB Wax, MK Patel, U Diaz, J Lin, DT AF Richmon, Jeremy D. Yarlagadda, Bharat B. Wax, Mark K. Patel, Urjeet Diaz, Jason Lin, Derrick T. TI Locoregional and free flap reconstruction of the lateral skull base SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review DE lateral skull base; free flap; locoregional reconstruction; complications; review ID TEMPORAL BONE DEFECTS; CEREBROSPINAL-FLUID LEAKS; FREE TISSUE TRANSFER; NECK RECONSTRUCTION; MANAGEMENT; COMPLICATIONS; OUTCOMES; CEMENT; HEAD AB Lateral temporal bone reconstruction after ablative surgery for malignancy, chronic infection, osteoradionecrosis, or trauma presents a challenge for the reconstructive surgeon. This complexity is due to the 3D nature of the region, potential dural exposure, and the possible need for external surface repair. Successful reconstruction therefore requires achieving separation of the dura, obliteration of volume defect, and external cutaneous repair. There is significant institutional bias on the best method of reconstruction of these defects. In this review, the advantages and disadvantages of reconstructive options will be discussed as well as the potential pitfalls and complications. (c) 2014 Wiley Periodicals, Inc. Head Neck 37: 1387-1391, 2015 C1 [Richmon, Jeremy D.] Johns Hopkins Univ, Dept Otolaryngol, Baltimore, MD USA. [Yarlagadda, Bharat B.; Lin, Derrick T.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Wax, Mark K.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. [Patel, Urjeet] Northwestern Univ, Dept Otolaryngol, Chicago, IL 60611 USA. [Diaz, Jason] Washington Univ, Dept Otolaryngol, St Louis, MO USA. RP Lin, DT (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM derrick_lin@meei.harvard.edu NR 22 TC 1 Z9 1 U1 0 U2 2 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 SEP PY 2015 VL 37 IS 9 BP 1387 EP 1391 DI 10.1002/hed.23725 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CP0ZN UT WOS:000359605700025 PM 24797502 ER PT J AU Macheret, F Bartz, TM Djousse, L Ix, JH Mukamal, KJ Zieman, SJ Siscovick, DS Tracy, RP Heckbert, SR Psaty, BM Kizer, JR AF Macheret, Fima Bartz, Traci M. Djousse, Luc Ix, Joachim H. Mukamal, Kenneth J. Zieman, Susan J. Siscovick, David S. Tracy, Russell P. Heckbert, Susan R. Psaty, Bruce M. Kizer, Jorge R. TI Higher circulating adiponectin levels are associated with increased risk of atrial fibrillation in older adults SO HEART LA English DT Article ID MOLECULAR-WEIGHT ADIPONECTIN; CHRONIC HEART-FAILURE; CARDIOVASCULAR HEALTH; INFLAMMATION; RESISTANCE; MORTALITY; DISEASE; MECHANISMS; STROKE; AGE AB Background Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner. Methods We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n= 3190; age= 74 +/- 5 years). Results During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1-76, the HR (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05 to 1.24), while that for HMW adiponectin was 1.17 (1.08 to 1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids and inflammation, did not significantly affect these estimates. Conclusions The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age. C1 [Macheret, Fima] Univ Penn, Sch Med, Penn Presbyterian Med Ctr, Dept Med, Philadelphia, PA USA. [Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Veteran Affairs San Diego Hlth Care Syst, Nephrol Sect, San Diego, CA USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Zieman, Susan J.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. [Tracy, Russell P.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Tracy, Russell P.] Univ Vermont, Dept Biochem, Burlington, VT 05405 USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA USA. [Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Kizer, JR (reprint author), Cardiovasc Clin Res Unit, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jorge.kizer@einstein.yu.edu FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [AG023629]; [R01 HL094555] FX This study was supported by R01 HL094555 (to Djousse, Ix, Kizer, Mukamal and Zieman). CHS supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086 and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/PI.htm. NR 30 TC 13 Z9 13 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD SEP PY 2015 VL 101 IS 17 BP 1368 EP 1374 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO9DH UT WOS:000359472300006 PM 25855796 ER PT J AU Berney, DM Algaba, F Amin, M Delahunt, B Comperat, E Epstein, JI Humphrey, P Idrees, M Lopez-Beltran, A Magi-Galluzzi, C Mikuz, G Montironi, R Oliva, E Srigley, J Reuter, VE Trpkov, K Ulbright, TM Varma, M Verrill, C Young, RH Zhou, M Egevad, L AF Berney, Daniel M. Algaba, Ferran Amin, Mahul Delahunt, Brett Comperat, Eva Epstein, Jonathan I. Humphrey, Peter Idrees, Mohammed Lopez-Beltran, Antonio Magi-Galluzzi, Cristina Mikuz, Gregor Montironi, Rodolfo Oliva, Esther Srigley, John Reuter, Victor E. Trpkov, Kiril Ulbright, Thomas M. Varma, Murali Verrill, Clare Young, Robert H. Zhou, Ming Egevad, Lars TI Handling and reporting of orchidectomy specimens with testicular cancer: areas of consensus and variation among 25 experts and 225 European pathologists SO HISTOPATHOLOGY LA English DT Article DE classification; consensus; germ cell tumour; rete testis; staging; testis ID GERM-CELL TUMORS; STAGE-I SEMINOMA; CLINICAL STAGE; LOW-RISK; SURVEILLANCE PROTOCOL; PROGNOSTIC-FACTORS; FOLLOW-UP; TESTIS; RELAPSE; TERATOMA AB AimsThe handling and reporting of testicular tumours is difficult due to their rarity. Methods and resultsA survey developed by the European Network of Uro-Pathology (ENUP) and sent to its members and experts to assess the evaluation of testicular germ cell tumours. Twenty-five experts and 225 ENUP members replied. Areas of disagreement included immaturity in teratomas, reported by 32% of experts but 68% of ENUP. Although the presence of rete testis invasion was reported widely, the distinction between pagetoid and stromal invasion was made by 96% of experts but only 63% of ENUP. Immunohistochemistry was used in more than 50% of cases by 68% of ENUP and 12% of experts. Staging revealed the greatest areas of disagreement. Invasion of the tunica vaginalis without vascular invasion was interpreted as T1 by 52% of experts and 67% of ENUP, but T2 by the remainder. Tumour invading the hilar adipose tissue adjacent to the epididymis without vascular invasion was interpreted as T1: 40% of experts, 43% of ENUP; T2: 36% of experts, 30% of ENUP; and T3: 24% of experts, 27% of ENUP. ConclusionsThere is remarkable consensus in many areas of testicular pathology. Significant areas of disagreement included staging and reporting of histological types, both of which have the potential to impact on therapy. C1 [Berney, Daniel M.] Queen Mary Univ London, Barts Canc Inst, London, England. [Algaba, Ferran] Fundacio Puigvert Univ Autonomous, Barcelona, Spain. [Amin, Mahul] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Delahunt, Brett] Wellington Sch Med & Hlth Sci, Dept Pathol, Wellington, New Zealand. [Delahunt, Brett] Univ Otago, Wellington, New Zealand. [Comperat, Eva] Hop La Pitie Salpetriere, Paris, France. [Epstein, Jonathan I.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Humphrey, Peter] Yale Univ, Sch Med, Yale New Haven Hosp, New Haven, CT USA. [Idrees, Mohammed; Ulbright, Thomas M.] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Idrees, Mohammed; Ulbright, Thomas M.] Indiana Pathol Inst, Indianapolis, IN USA. [Lopez-Beltran, Antonio] Univ Cordoba, Sch Med, Cordoba, Spain. [Magi-Galluzzi, Cristina] Cleveland Clin, Robert J Tomsich Pathol & Lab Med Inst, Cleveland, OH 44106 USA. [Mikuz, Gregor] Med Univ Innsbruck, Inst Pathol, A-6020 Innsbruck, Austria. [Montironi, Rodolfo] Polytech Univ Marche Reg, Ancona, Italy. [Oliva, Esther; Young, Robert H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Srigley, John] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Reuter, Victor E.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Trpkov, Kiril] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada. [Trpkov, Kiril] Calgary Lab Serv, Calgary, AB, Canada. [Varma, Murali] Univ Wales Hosp, Cardiff CF4 4XW, S Glam, Wales. [Verrill, Clare] John Radcliffe Hosp, Dept Cellular Pathol, Oxford OX3 9DU, England. [Zhou, Ming] NYU, Langone Med Ctr, Dept Pathol, New York, NY USA. [Egevad, Lars] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. RP Berney, DM (reprint author), John Vane Sci Ctr, Barts Canc Inst, Charterhouse Sq, London EC1M 6BQ, England. EM D.Berney@bartshealth.nhs.uk OI Berney, Daniel/0000-0001-5474-8696 FU Orchid FX We gratefully acknowledge the other experts who took part in the survey: Phillippe Camparo, Jeffrey Theaker, Isabell Sesterhenn and Grete Krag Jacobsen. D.B. gratefully acknowledges the support of Orchid. NR 39 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-0167 EI 1365-2559 J9 HISTOPATHOLOGY JI Histopathology PD SEP PY 2015 VL 67 IS 3 BP 313 EP 324 DI 10.1111/his.12657 PG 12 WC Cell Biology; Pathology SC Cell Biology; Pathology GA CP1WW UT WOS:000359669200004 PM 25619976 ER PT J AU Farrand, AJ Haley, KP Lareau, NM Heilbronner, S McLean, JA Foster, T Skaar, EP AF Farrand, Allison J. Haley, Kathryn P. Lareau, Nichole M. Heilbronner, Simon McLean, John A. Foster, Timothy Skaar, Eric P. TI An Iron-Regulated Autolysin Remodels the Cell Wall To Facilitate Heme Acquisition in Staphylococcus lugdunensis SO INFECTION AND IMMUNITY LA English DT Article ID SURFACE-PROTEINS; LYTIC TRANSGLYCOSYLASES; N-ACETYLGLUCOSAMINIDASE; HEMOGLOBIN BINDING; ANCHOR STRUCTURE; AUREUS HEME; SORTASE; BACTERIAL; ISDC; PATHOGENESIS AB Bacteria alter their cell surface in response to changing environments, including those encountered upon invasion of a host during infection. One alteration that occurs in several Gram-positive pathogens is the presentation of cell wall-anchored components of the iron-regulated surface determinant (Isd) system, which extracts heme from host hemoglobin to fulfill the bacterial requirement for iron. Staphylococcus lugdunensis, an opportunistic pathogen that causes infective endocarditis, encodes an Isd system. Unique among the known Isd systems, S. lugdunensis contains a gene encoding a putative autolysin located adjacent to the Isd operon. To elucidate the function of this putative autolysin, here named IsdP, we investigated its contribution to Isd protein localization and hemoglobin-dependent iron acquisition. S. lugdunensis IsdP was found to be iron regulated and cotranscribed with the Isd operon. IsdP is a specialized peptidoglycan hydrolase that cleaves the stem peptide and pentaglycine cross-bridge of the cell wall and alters processing and anchoring of a major Isd system component, IsdC. Perturbation of IsdC localization due to isdP inactivation results in a hemoglobin utilization growth defect. These studies establish IsdP as an autolysin that functions in heme acquisition and describe a role for IsdP in cell wall reorganization to accommodate nutrient uptake systems during infection. C1 [Farrand, Allison J.; Haley, Kathryn P.; Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. [Lareau, Nichole M.; McLean, John A.] Vanderbilt Univ, Dept Chem, Ctr Innovat Technol, Inst Chem Biol, Nashville, TN USA. [Lareau, Nichole M.; McLean, John A.] Vanderbilt Univ, Inst Integrat Biosyst Res & Educ, Nashville, TN 37235 USA. [Heilbronner, Simon; Foster, Timothy] Trinity Coll Dublin, Moyne Inst Prevent Med, Dept Microbiol, Dublin, Ireland. [Skaar, Eric P.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN USA. RP Skaar, EP (reprint author), Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. EM eric.skaar@vanderbilt.edu FU NIH [RO1 AI069233, RO1 AI101171]; NIAID; Department of Veterans Affairs Merit Award [INFB-024-13F]; National Institutes of Health [R01GM092218]; Vanderbilt Chemical Biology Interface training program [5RT32GM065086] FX This research was supported by NIH RO1 AI069233, funded by the NIAID ( E.P.S.). The Skaar laboratory is also supported by Department of Veterans Affairs Merit Award INFB-024-13F and NIH RO1 AI101171. Funding for J.A.M. and N.M.L. was provided by the National Institutes of Health (R01GM092218). Additional funding for N.M.L. was provided by the Vanderbilt Chemical Biology Interface training program (5RT32GM065086) supported by the NIH. NR 49 TC 4 Z9 4 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2015 VL 83 IS 9 BP 3578 EP 3589 DI 10.1128/IAI.00397-15 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CO8QP UT WOS:000359435600023 PM 26123800 ER PT J AU Bernhardt, J Salinas, J Schwamm, L AF Bernhardt, J. Salinas, J. Schwamm, L. TI Defining an international standard set of patient-centered outcome measures after stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Bernhardt, J.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia. [Salinas, J.; Schwamm, L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD SEP PY 2015 VL 10 SU 3 SI SI BP 54 EP 54 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YR UT WOS:000359304400139 ER PT J AU Farrar, CT DePeralta, DK Day, H Rietz, TA Wei, L Lauwers, GY Keil, B Subramaniam, A Sinskey, AJ Tanabe, KK Fuchs, BC Caravan, P AF Farrar, Christian T. DePeralta, Danielle K. Day, Helen Rietz, Tyson A. Wei, Lan Lauwers, Gregory Y. Keil, Boris Subramaniam, Arun Sinskey, Anthony J. Tanabe, Kenneth K. Fuchs, Bryan C. Caravan, Peter TI 3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model SO JOURNAL OF HEPATOLOGY LA English DT Article DE Liver fibrosis; Type I collagen; Molecular imaging; Non-invasive; MRI; EP-3533; Bile duct ligation (BDL) ID MAGNETIC-RESONANCE ELASTOGRAPHY; HEPATIC-FIBROSIS; TRANSIENT ELASTOGRAPHY; CLINICAL-APPLICATIONS; CONTRAST AGENT; DISEASE; COLLAGEN; BIOPSY; COMPLICATIONS; FIBROGENESIS AB Background & Aims: Liver biopsy, the gold standard for assessing liver fibrosis, suffers from limitations due to sampling error and invasiveness. There is therefore a critical need for methods to non-invasively quantify fibrosis throughout the entire liver. The goal of this study was to use molecular Magnetic Resonance Imaging (MRI) of Type I collagen to non-invasively image liver fibrosis and assess response to rapamycin therapy. Methods: Liver fibrosis was induced in rats by bile duct ligation (BDL). MRI was performed 4, 10, or 18 days following BDL. Some BDL rats were treated daily with rapamycin starting on day 4 and imaged on day 18. A three-dimensional (3D) inversion recovery MRI sequence was used to quantify the change in liver longitudinal relaxation rate (Delta R1) induced by the collagen-targeted probe EP-3533. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed for Sirius Red staining and hydroxyproline content. Results: Delta R1 increased significantly with time following BDL compared to controls in agreement with ex vivo measures of increasing fibrosis. Receiver operating characteristic curve analysis demonstrated the ability of Delta R1 to detect liver fibrosis and distinguish intermediate and late stages of fibrosis. EP-3533 MRI correctly characterized the response to rapamycin in 11 out of 12 treated rats compared to the standard of collagen proportional area (CPA). 3D MRI enabled characterization of disease heterogeneity throughout the whole liver. Conclusions: EP-3533 allowed for staging of liver fibrosis, assessment of response to rapamycin therapy, and demonstrated the ability to detect heterogeneity in liver fibrosis. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Farrar, Christian T.; Day, Helen; Rietz, Tyson A.; Keil, Boris; Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Farrar, Christian T.; Day, Helen; Rietz, Tyson A.; Keil, Boris; Caravan, Peter] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [DePeralta, Danielle K.; Wei, Lan; Tanabe, Kenneth K.; Fuchs, Bryan C.] Massachusetts Gen Hosp, Ctr Canc, Surg Oncol, Boston, MA 02114 USA. [DePeralta, Danielle K.; Wei, Lan; Lauwers, Gregory Y.; Tanabe, Kenneth K.; Fuchs, Bryan C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Subramaniam, Arun] Sanofi Genzyme, Framingham, MA 01701 USA. [Sinskey, Anthony J.] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM bfuchs@mgh.harvard.edu; caravan@nmr.mgh.harvard.edu FU National Cancer Institute [CA140861, DK104956]; National Institute of Biomedical Imaging and Bioengineering [EB009062]; Innovation Award from Sanofi FX This work was supported by grants from the National Cancer Institute (CA140861 and DK104956 (B.C.F.)), the National Institute of Biomedical Imaging and Bioengineering (EB009062 (P.C.)), and an Innovation Award from Sanofi (A.J.S and P.C.). NR 42 TC 6 Z9 6 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD SEP PY 2015 VL 63 IS 3 BP 689 EP 696 DI 10.1016/j.jhep.2015.04.029 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP2QI UT WOS:000359721700019 PM 26022693 ER PT J AU Doan, H Chinn, GM Jahan-Tigh, RR AF Doan, Hung Chinn, Garrett M. Jahan-Tigh, Richard R. TI Flow Cytometry II: Mass and Imaging Cytometry SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material C1 [Doan, Hung; Jahan-Tigh, Richard R.] Univ Texas Houston, Houston Med Sch, Dept Dermatol, Houston, TX USA. [Doan, Hung; Jahan-Tigh, Richard R.] Univ Texas MD Anderson Canc Ctr, Dept Med, Div Dermatol, Houston, TX 77030 USA. [Chinn, Garrett M.] Harvard Univ, Sch Med, Div Gen Internal Med, Massachusetts Gen Hosp, Boston, MA USA. RP Jahan-Tigh, RR (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Dermatol, 6655 Travis St,Suite 980, Houston, TX 77030 USA. EM Richard.R.Jahantigh@uth.tmc.edu FU Duke University School of Medicine; Society for Investigative Dermatology FX This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the Duke University School of Medicine and Society for Investigative Dermatology. The Duke University School of Medicine is accredited by the ACCME to provide continuing medical education for physicians. To participate in the CME activity, follow the link provided. Physicians should only claim credit commensurate with the extent of their participation in the activity. NR 11 TC 3 Z9 4 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2015 VL 135 IS 9 BP 1 EP 4 DI 10.1038/jid.2015.263 PG 4 WC Dermatology SC Dermatology GA CO9JR UT WOS:000359492100001 PM 26269409 ER PT J AU Jalian, HR Tam, J Vuong, LN Fisher, J Garibyan, L Mihm, MC Zurakowski, D Evans, CL Anderson, RR AF Jalian, H. Ray Tam, Joshua Vuong, Linh N. Fisher, Jeremy Garibyan, Lilit Mihm, Martin C. Zurakowski, David Evans, Conor L. Anderson, R. Rox TI Selective Cryolysis of Sebaceous Glands SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID ACNE-VULGARIS; ACID; THERAPY; VESSELS; CELLS; MICE; SKIN AB Acne vulgaris is a nearly universal cutaneous inflammatory disease. Excess sebum production is an integral part of disease pathogenesis. Medical therapies that reduce sebum excretion result in clinical improvement of acne. Given the preferential susceptibility of lipid-containing cells to cold, we investigated the hypothesis that controlled local skin cooling causes preferential injury to sebaceous glands, in murine and swine models using a range of temperatures as low as -10 degrees C, and then on the backs of human subjects. In mouse ears, peak histologic damage occurred 72 hours after treatment; eosinophilic necrotic plugs formed within sebaceous glands, and the number of glands was significantly reduced up to 1 week post treatment. Cooling disrupted sebocyte cell membranes, alkaline phosphatase activity, and significantly reduced sebocyte lipid content. In human volunteers, cooling damaged sebaceous glands and reduced sebum output for 2 weeks, with minimal injury to surrounding tissues. Selective cryolysis of sebaceous glands is achievable through brief, non-invasive skin cooling, suggesting that controlled cooling could be developed as an effective treatment for acne vulgaris. C1 [Jalian, H. Ray] Univ Calif Los Angeles, Dept Med, Div Dermatol, Los Angeles, CA 90024 USA. [Jalian, H. Ray; Tam, Joshua; Vuong, Linh N.; Fisher, Jeremy; Garibyan, Lilit; Evans, Conor L.; Anderson, R. Rox] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tam, Joshua; Garibyan, Lilit; Evans, Conor L.; Anderson, R. Rox] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Mihm, Martin C.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Sch Med, Dept Surg, Childrens Hosp Boston, Boston, MA 02115 USA. RP Jalian, HR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St,Thier 2,Room 204, Boston, MA 02114 USA. EM HRJalian@mgh.harvard.edu FU Zeltiq Aesthetics (Pleasanton, CA) FX Zeltiq Aesthetics (Pleasanton, CA) provided cooling devices and partial research funding for these experiments. RRA receives a portion of royalties from Massachusetts General Hospital derived from Zeltiq. HRJ, JT, and RRA are inventors in patent applications filed from MGH, in part based on technology described in this manuscript. The remaining authors state no conflict of interest. NR 23 TC 0 Z9 0 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2015 VL 135 IS 9 BP 2173 EP 2180 DI 10.1038/jid.2015.148 PG 8 WC Dermatology SC Dermatology GA CO9JR UT WOS:000359492100008 PM 25860384 ER PT J AU Hinde, E Foster, A Imanishi, A Schneider, MR Kawai, K Matos, TR Haslam, I Paus, R AF Hinde, E. Foster, A. Imanishi, A. Schneider, M. R. Kawai, K. Matos, T. R. Haslam, I. Paus, R. TI The sebaceous gland shows differential responses to spontaneous and induced cycling SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 09-12, 2015 CL Rotterdam, NETHERLANDS SP European Soc Dermatol Res C1 [Hinde, E.; Foster, A.; Imanishi, A.; Haslam, I.; Paus, R.] Univ Manchester, Inst Inflammat & Repair, Manchester, Lancs, England. [Schneider, M. R.] Ludwig Maximilians Univ Munchen, Inst Mol Anim Breeding & Biotechnol, Munich, Germany. [Matos, T. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Kawai, K.] Kido Hosp, Dept Dermatol, Niigata, 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 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2015 VL 135 SU 2 MA 400 BP S69 EP S69 PG 1 WC Dermatology SC Dermatology GA CP2WW UT WOS:000359739400400 ER PT J AU Marneros, AG AF Marneros, A. G. TI Familial aplasia cutis congenita is caused by a defect in ribosome biogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 09-12, 2015 CL Rotterdam, NETHERLANDS SP European Soc Dermatol Res C1 [Marneros, A. G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatol, Charlestown, 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 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2015 VL 135 SU 2 MA 320 BP S55 EP S55 PG 1 WC Dermatology SC Dermatology GA CP2WW UT WOS:000359739400321 ER PT J AU Koerte, IK Lin, AP Muehlmann, M Merugumala, S Liao, HJ Starr, T Kaufmann, D Mayinger, M Steffinger, D Fisch, B Karch, S Heinen, F Ertl-Wagner, B Reiser, M Stern, RA Zafonte, R Shenton, ME AF Koerte, Inga K. Lin, Alexander P. Muehlmann, Marc Merugumala, Sai Liao, Huijun Starr, Tyler Kaufmann, David Mayinger, Michael Steffinger, Denise Fisch, Barbara Karch, Susanne Heinen, Florian Ertl-Wagner, Birgit Reiser, Maximilian Stern, Robert A. Zafonte, Ross Shenton, Martha E. TI Altered Neurochemistry in Former Professional Soccer Players without a History of Concussion SO JOURNAL OF NEUROTRAUMA LA English DT Article DE brain metabolism; repetitive subconcussive brain trauma; MR spectroscopy; soccer ID TRAUMATIC BRAIN-INJURY; MAGNETIC-RESONANCE-SPECTROSCOPY; MILD COGNITIVE IMPAIRMENT; MYOINOSITOL; DEFICITS; TRAIL; RISK AB Soccer is played by more than 250 million people worldwide. Repeatedly heading the ball may place soccer players at high risk for repetitive subconcussive head impacts (RSHI). This study evaluates the long-term effects of RSHI on neurochemistry in athletes without a history of clinically diagnosed concussion, but with a high exposure to RSHI. Eleven former professional soccer players (mean age 52.0 +/- 6.8 years) and a comparison cohort of 14 age- and gender-matched, former non-contact sport athletes (mean age 46.9 +/- 7.9 years) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation. In the soccer players a significant increase was observed in both choline (Cho), a membrane marker, and myo-inositol (ml), a marker of glial activation, compared with control athletes. Additionally, ml and glutathione (GSH) were significantly correlated with lifetime estimate of RSHI within the soccer group. There was no significant difference in neurocognitive tests between groups. Results of this study suggest an association between RSHI in soccer players and MRS markers of neuroinflammation, suggesting that even subconcussive head impacts affect the neurochemistry of the brain and may precede neurocognitive changes. Future studies will need to determine the role of neuroinflammation in RSHI and the effect on neurocognitive function. C1 [Koerte, Inga K.; Lin, Alexander P.; Muehlmann, Marc; Mayinger, Michael; Shenton, Martha E.] Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Lin, Alexander P.; Merugumala, Sai; Liao, Huijun; Starr, Tyler; Shenton, Martha E.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Shenton, Martha E.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02215 USA. [Shenton, Martha E.] Harvard Univ, Sch Med, Boston, MA USA. [Koerte, Inga K.; Muehlmann, Marc; Kaufmann, David; Mayinger, Michael; Steffinger, Denise; Fisch, Barbara; Ertl-Wagner, Birgit; Reiser, Maximilian] Univ Munich, Dr von Hauner Childrens Hospital, Inst Clin Radiol, Munich, Germany. [Koerte, Inga K.; Muehlmann, Marc] Univ Munich, Dr von Hauner Childrens Hospital, Dept Child & Adolescent Psychiat Psychosomat & Ps, Munich, Germany. [Karch, Susanne] Univ Munich, Dept Psychiat, Dr von Hauner Childrens Hospital, D-80539 Munich, Germany. [Heinen, Florian] Univ Munich, Dr von Hauner Childrens Hospital, Dept Pediat Neurol, Munich, Germany. [Kaufmann, David] Charite, Dept Radiol, Berlin, Germany. [Stern, Robert A.] Boston Univ, Sch Med, Dept Neurol, Boston Univ Alzheimers Dis Ctr, Boston, MA 02118 USA. [Stern, Robert A.] Boston Univ, Sch Med, Boston Univ Alzheimers Dis Ctr, Dept Neurosurg, Boston, MA 02118 USA. [Stern, Robert A.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston Univ Alzheimers Dis Ctr, Boston, MA 02118 USA. [Zafonte, Ross] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Spaulding Rehabil Hosp,Dept Phys Med & Rehabil,Sc, Boston, MA 02115 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Boston, MA USA. RP Koerte, IK (reprint author), Brigham & Womens Hosp, Psychiat Neuroimaging Lab, 1249 Boylston St, Boston, MA 02215 USA. EM ikoerte@bwh.harvard.edu OI Stern, Robert/0000-0002-5008-077X FU Else Kroner-Fresenius-Stiftung, Germany; Department of Defense [W81XWH-10-1-0835, W81XWH-07-CC-CSDoD]; National Institutes of Health [R01-NS078337]; VA Merit Award; Petraeic Legate Foundation, Germany FX This study was supported by the Else Kroner-Fresenius-Stiftung, Germany (I.K.). This work was also partially funded by grants from the Department of Defense (W81XWH-10-1-0835: A.P.L.; W81XWH-07-CC-CSDoD: R.Z., M.E.S.), the National Institutes of Health (R01-NS078337: A.P.L., M.E.S., R.A.S.) and a VA Merit Award (M.E.S.). Michael Mayinger was supported by the Petraeic Legate Foundation, Germany. NR 42 TC 12 Z9 12 U1 6 U2 28 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP 1 PY 2015 VL 32 IS 17 BP 1287 EP 1293 DI 10.1089/neu.2014.3715 PG 7 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CP0KP UT WOS:000359564500001 PM 25843317 ER PT J AU Dretsch, MN Silverberg, ND Iverson, GL AF Dretsch, Michael N. Silverberg, Noah D. Iverson, Grant L. TI Multiple Past Concussions Are Associated with Ongoing Post-Concussive Symptoms but Not Cognitive Impairment in Active-Duty Army Soldiers SO JOURNAL OF NEUROTRAUMA LA English DT Article DE post-concussion symptoms; military; concussion; neurocognitive; PTSD ID TRAUMATIC BRAIN-INJURY; PROFESSIONAL FOOTBALL PLAYERS; POSTTRAUMATIC-STRESS-DISORDER; NEUROPSYCHOLOGICAL PERFORMANCE; POSTCONCUSSIVE SYMPTOMS; RECURRENT CONCUSSION; IRAQI FREEDOM; HISTORY; INSTRUMENT; TBI AB The extent to which multiple past concussions are associated with lingering symptoms or mental health problems in military service members is not well understood. The purpose of this study was to examine the association between lifetime concussion history, cognitive functioning, general health, and psychological health in a large sample of fit-for-duty U.S. Army soldiers preparing for deployment. Data on 458 active-duty soldiers were collected and analyzed. A computerized cognitive screening battery (CNS-Vital Signs((R))) was used to assess complex attention (CA), reaction time (RT), processing speed (PS), cognitive flexibility (CF), and memory. Health questionnaires included the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Military Version (PCL-M), Zung Depression and Anxiety Scales (ZDS; ZAS), Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the Alcohol Use and Dependency Identification Test (AUDIT). Soldiers with a history of multiple concussions (i.e., three or more concussions) had significantly greater post-concussive symptom scores compared with those with zero (d=1.83, large effect), one (d=0.64, medium effect), and two (d=0.64, medium effect) prior concussions. Although the group with three or more concussions also reported more traumatic stress symptoms, the results revealed that traumatic stress was a mediator between concussions and post-concussive symptom severity. There were no significant differences on neurocognitive testing between the number of concussions. These results add to the accumulating evidence suggesting that most individuals recover from one or two prior concussions, but there is a greater risk for ongoing symptoms if one exceeds this number of injuries. C1 [Dretsch, Michael N.] US Army Aeromed Res Lab, Ft Rucker, AL USA. [Dretsch, Michael N.] Walter Reed Natl Mil Med Ctr, Natl Intrepid Ctr Excellence, Bethesda, MD 20889 USA. [Silverberg, Noah D.] Univ British Columbia, Div Phys Med & Rehabil, Vancouver, BC V5Z 1M9, Canada. [Silverberg, Noah D.] GF Strong Rehab Ctr, Vancouver, BC, Canada. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Iverson, Grant L.] Def & Vet Brain Injury Ctr, Bethesda, MD USA. RP Dretsch, MN (reprint author), Walter Reed Natl Mil Med Ctr, Natl Intrepid Ctr Excellence, 4860 South Palmer Rd, Bethesda, MD 20889 USA. EM Michael.n.dretsch.mil@mail.mil FU U.S. Army Medical Research and Materiel Command; INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium - Department of Defense Psychological Health/Traumatic Brain Injury Research Program [X81XWH-07-CC-CSDoD]; U.S. Army Aeromedical Research Laboratory FX The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Defense or the U.S. government. Primary funding for this study was provided by the U.S. Army Medical Research and Materiel Command (provided to Dr. Michael Dretsch as the PI). Dr. Grant Iverson notes that this work was supported in part by the INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium funded by the Department of Defense Psychological Health/Traumatic Brain Injury Research Program (X81XWH-07-CC-CSDoD). The authors wish to thank the U.S. Army Aeromedical Research Laboratory for its support during the time this study was conducted. Preliminary findings from this study were presented at the 2014 Annual Military Health System Research Symposium, Fort Lauderdale, FL. NR 42 TC 2 Z9 2 U1 7 U2 20 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP 1 PY 2015 VL 32 IS 17 BP 1301 EP 1306 DI 10.1089/neu.2014.3810 PG 6 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CP0KP UT WOS:000359564500003 PM 25763565 ER PT J AU Cook, NE Freeman, JB Garcia, AM Sapyta, JJ Franklin, ME AF Cook, Nathan E. Freeman, Jennifer B. Garcia, Abbe M. Sapyta, Jeffrey J. Franklin, Martin E. TI Assessment of Obsessive Compulsive Disorder in Young Children: Psychometric Properties of the Children's Yale-Brown Obsessive Compulsive Scale SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Obsessive-compulsive disorder; Psychometrics; Reliability; Construct validity ID RELIABILITY; VALIDITY; ALPHA AB The Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) is the most commonly used instrument to assess the symptoms and severity of pediatric obsessive compulsive disorder (OCD). However, only one prior study has evaluated the psychometric properties of the CY-BOCS for assessing young children, ages 5 to 8 years. The limited available evidence suggests that psychometric properties are less favorable with younger children. Thus, the present study aimed to re-examine the technical qualities of the CY-BOCS in a sample of 5 to 8 year olds with early-onset OCD. The sample consisted of 127 younger children, enrolled in a multi-site randomized controlled trial comparing the efficacy of family-based cognitive behavioral therapy to relaxation therapy. The CY-BOCS Total score demonstrated adequate internal consistency, although at a lower level than is typically reported in studies of older children. Internal consistency of the Obsessions and Compulsions subscales was poor. The Total and subscale scores demonstrated good temporal stability over 5 weeks. Agreement between clinician and parent versions was poor at baseline but improved substantially throughout the course of the trial. Results also indicated that the CY-BOCS had good convergent and discriminant validity. Further, certain CY-BOCS items appear more reliable indicators of OCD severity in younger children than others. Limitations, implications, and future directions are discussed, including the potential for further developmentally sensitive refinement of the CY-BOCS for this age group. C1 [Cook, Nathan E.] Univ Rhode Isl, Dept Psychol, Kingston, RI 02881 USA. [Freeman, Jennifer B.; Garcia, Abbe M.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Bradley Hasbro Childrens Res Ctr, Providence, RI 02912 USA. [Sapyta, Jeffrey J.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Franklin, Martin E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Cook, Nathan E.] Massachusetts Gen Hosp, Dept Psychiat, Learning & Emot Assessment Program, Boston, MA USA. RP Cook, NE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM necook@mgh.harvard.edu NR 28 TC 1 Z9 1 U1 4 U2 16 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD SEP PY 2015 VL 37 IS 3 BP 432 EP 441 DI 10.1007/s10862-014-9465-7 PG 10 WC Psychology, Clinical SC Psychology GA CO7RN UT WOS:000359359400006 ER PT J AU Bril, F Ortiz-Lopez, C Lomonaco, R Orsak, B Freckleton, M Chintapalli, K Hardies, J Lai, S Solano, F Tio, F Cusi, K AF Bril, Fernando Ortiz-Lopez, Carolina Lomonaco, Romina Orsak, Beverly Freckleton, Michael Chintapalli, Kedar Hardies, Jean Lai, Song Solano, Felipe Tio, Fermin Cusi, Kenneth TI Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients SO LIVER INTERNATIONAL LA English DT Article DE hepatic steatosis; NAFLD; NASH; Obesity; steatohepatitis ID MAGNETIC-RESONANCE-SPECTROSCOPY; HEPATIC STEATOSIS; METABOLIC PARAMETERS; INSULIN-RESISTANCE; STEATOHEPATITIS; PREVALENCE; NAFLD; ULTRASONOGRAPHY; HISTOLOGY; ACCURACY AB Background & AimsLiver ultrasound (US) is usually used in the clinical setting for the diagnosis and follow-up of patients with nonalcoholic fatty liver disease (NAFLD). However, no large study has carefully assessed its performance using a semiquantitative ultrasonographic scoring system in overweight/obese patients, in comparison to magnetic resonance spectroscopy (H-1-MRS) and histology. MethodsWe recruited 146 patients and performed: a liver US using a 5-parameter scoring system, a liver H-1-MRS to quantify liver fat content, and a liver biopsy to assess histology. All measurements were repeated in a subgroup of patients (n=62) after 18months of follow-up. ResultsThe performance of liver US (parenchymal echo alone) was rather modest, and significantly worse than H-1-MRS (AUROC: 0.82 [0.69-0.94] vs. 0.96 [0.90-1.00]; P=0.04). However, the AUROC improved when different echographic parameters were taken into account (AUROC: 0.89 [0.83-0.96], P=0.15 against H-1-MRS). Optimum sensitivity for liver US was achieved at a liver fat content 12.5%, suggesting that below this threshold, liver US is less sensitive. Liver H-1-MRS showed a high accuracy for the diagnosis of NAFLD, and correlated strongly with histological steatosis (r=0.73, P<0.0001). None of the imaging tests was adequate enough to predict changes over time in histology. ConclusionsDespite its widespread use, liver US has several important limitations that healthcare providers should recognize, particularly because of its low sensitivity. Using a combination of echographic parameters, liver US showed a significant improvement in its diagnostic performance, but still was of limited value for monitoring treatment over time. C1 [Bril, Fernando; Lomonaco, Romina; Cusi, Kenneth] Univ Florida, Div Endocrinol Diabet & Metab, Gainesville, FL 32610 USA. [Bril, Fernando; Lomonaco, Romina; Cusi, Kenneth] Malcom Randall Vet Adm Med Ctr, Gainesville, FL USA. [Ortiz-Lopez, Carolina; Orsak, Beverly; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, San Antonio, TX 78229 USA. [Freckleton, Michael; Chintapalli, Kedar; Hardies, Jean] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Lai, Song] Univ Florida, McKnight Brain Inst, Clin Translat Sci Inst, Human Imaging Core, Gainesville, FL 32610 USA. [Solano, Felipe; Tio, Fermin] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Cusi, Kenneth] Audie L Murphy Vet Adm Med Ctr, San Antonio, TX USA. RP Cusi, K (reprint author), Univ Florida, Div Endocrinol Diabet & Metab, 1600 SW Archer Rd,Room H-2, Gainesville, FL 32610 USA. EM Kenneth.Cusi@medicine.ufl.edu FU Burroughs Wellcome Fund; American Diabetes Association [1-08-CR-08]; VA Merit Award [1 I01 CX000167-01] FX Financial support: Supported by the Burroughs Wellcome Fund (K. C.), the American Diabetes Association (1-08-CR-08 [K. C.]) and a VA Merit Award (1 I01 CX000167-01 [K. C.]). NR 33 TC 19 Z9 19 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-3223 EI 1478-3231 J9 LIVER INT JI Liver Int. PD SEP PY 2015 VL 35 IS 9 BP 2139 EP 2146 DI 10.1111/liv.12840 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP2KI UT WOS:000359705500011 PM 25847730 ER PT J AU Gensheimer, MF Hummel-Kramer, SM Cain, D Quang, TS AF Gensheimer, Michael F. Hummel-Kramer, Sharon M. Cain, David Quang, Tony S. TI Simple tool for prediction of parotid gland sparing in intensity-Modulated radiation therapy SO MEDICAL DOSIMETRY LA English DT Article DE IMRT; Parotid gland; Head and neck cancer; Process improvement ID VOLUME; IMRT; HEAD AB Sparing one or both parotid glands is a key goal when planning head and neck cancer radiation treatment. If the planning target volume (PTV) overlaps one or both parotid glands substantially, it may not be possible to achieve adequate gland sparing. This finding results in physicians revising their PTV contours after an intensity-modulated radiation therapy (IMRT) plan has been run and reduces workflow efficiency. We devised a simple formula for predicting mean parotid gland dose from the overlap of the parotid gland and isotropically expanded PTV contours. We tested the tool using 44 patients from 2 institutions and found agreement between predicted and actual parotid gland doses (mean absolute error = 5.3 Gy). This simple method could increase treatment planning efficiency by improving the chance that the first plan presented to the physician will have optimal parotid gland sparing. Published by Elsevier Inc. on behalf of American Association of Medical Dosimetrists C1 [Gensheimer, Michael F.] Univ Washington, Med Ctr, Dept Radiat Oncol, Seattle, WA 98195 USA. [Hummel-Kramer, Sharon M.; Cain, David; Quang, Tony S.] VA Puget Sound Hlth Care Syst, Dept Radiat Oncol, Seattle, WA 98108 USA. RP Hummel-Kramer, SM (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,Mail Stop S-111 RadOnc, Seattle, WA 98108 USA. EM sharonhummel@comcast.net FU Department of Veterans Affairs FX We thank Drs. Upendra Parvathaneni and Jay Liao at the University of Washington for allowing us to include their patients in this study. This research was conducted with support from the Department of Veterans Affairs. NR 6 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0958-3947 EI 1873-4022 J9 MED DOSIM JI Med. Dosim. PD FAL PY 2015 VL 40 IS 3 BP 232 EP 234 DI 10.1016/j.meddos.2015.01.002 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CO8VD UT WOS:000359449400012 PM 25704638 ER PT J AU Logue, MW Amstadter, AB Baker, DG Duncan, L Koenen, KC Liberzon, I Miller, MW Morey, RA Nievergelt, CM Ressler, KJ Smith, AK Smoller, JW Stein, MB Sumner, JA Uddin, M AF Logue, Mark W. Amstadter, Ananda B. Baker, Dewleen G. Duncan, Laramie Koenen, Karestan C. Liberzon, Israel Miller, Mark W. Morey, Rajendra A. Nievergelt, Caroline M. Ressler, Kerry J. Smith, Alicia K. Smoller, Jordan W. Stein, Murray B. Sumner, Jennifer A. Uddin, Monica TI The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup: Posttraumatic Stress Disorder Enters the Age of Large-Scale Genomic Collaboration SO NEUROPSYCHOPHARMACOLOGY LA English DT Review ID GENE-ENVIRONMENT INTERACTIONS; TWIN VET REGISTRY; WIDE ASSOCIATION; MAJOR DEPRESSION; TRAUMATIC EVENTS; RISK LOCI; EXPOSURE; PTSD; IDENTIFICATION; POPULATION AB The development of posttraumatic stress disorder (PTSD) is influenced by genetic factors. Although there have been some replicated candidates, the identification of risk variants for PTSD has lagged behind genetic research of other psychiatric disorders such as schizophrenia, autism, and bipolar disorder. Psychiatric genetics has moved beyond examination of specific candidate genes in favor of the genome-wide association study (GWAS) strategy of very large numbers of samples, which allows for the discovery of previously unsuspected genes and molecular pathways. The successes of genetic studies of schizophrenia and bipolar disorder have been aided by the formation of a large-scale GWAS consortium: the Psychiatric Genomics Consortium (PGC). In contrast, only a handful of GWAS of PTSD have appeared in the literature to date. Here we describe the formation of a group dedicated to large-scale study of PTSD genetics: the PGC-PTSD. The PGC-PTSD faces challenges related to the contingency on trauma exposure and the large degree of ancestral genetic diversity within and across participating studies. Using the PGC analysis pipeline supplemented by analyses tailored to address these challenges, we anticipate that our first large-scale GWAS of PTSD will comprise over 10 000 cases and 30 000 trauma-exposed controls. Following in the footsteps of our PGC forerunners, this collaboration-of a scope that is unprecedented in the field of traumatic stress-will lead the search for replicable genetic associations and new insights into the biological underpinnings of PTSD. C1 [Logue, Mark W.] VA Boston Healthcare Syst, Res, Boston, MA 02130 USA. [Logue, Mark W.] Boston Univ, Sch Med, Biomed Genet, Boston, MA 02118 USA. [Logue, Mark W.] Boston Univ, Sch Publ Hlth, Biostat, Boston, MA USA. [Amstadter, Ananda B.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Baker, Dewleen G.; Nievergelt, Caroline M.; Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Baker, Dewleen G.; Nievergelt, Caroline M.] VA Ctr Excellence Stress & Mental Hlth CESAMH, VA San Diego Healthcare Syst, La Jolla, CA USA. [Duncan, Laramie] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Duncan, Laramie] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Psychiat & Neurodev Genet, Boston, MA 02114 USA. [Duncan, Laramie] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA USA. [Koenen, Karestan C.; Sumner, Jennifer A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Liberzon, Israel] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Liberzon, Israel] Vet Affairs Ann Arbor Hlth Syst, Ann Arbor, MI USA. [Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Morey, Rajendra A.] Duke Univ, Med Ctr, Duke UNC Brain Imaging & Anal Ctr, Durham, NC USA. [Morey, Rajendra A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Morey, Rajendra A.] Durham VA Med Ctr, Mental Illness Res Educ & Clin Ctr Post Deploymen, Durham, NC USA. [Ressler, Kerry J.; Smith, Alicia K.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Ressler, Kerry J.] Yerkes Natl Primate Res Ctr, Ctr Behav Neurosci, Atlanta, GA USA. [Ressler, Kerry J.] Howard Hughes Med Inst, Bethesda, MD 20817 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Smoller, Jordan W.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Smoller, Jordan W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Uddin, Monica] Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL USA. [Uddin, Monica] Univ Illinois, Dept Psychol, Champaign, IL USA. RP Logue, MW (reprint author), VA Boston Healthcare Syst, Mail Stop 151C,150 South Huntington Ave, Boston, MA 02130 USA. EM Mark.Logue@va.gov OI Miller, Mark/0000-0001-6393-8563; Nievergelt, Caroline/0000-0001-5766-8923; Liberzon, Israel/0000-0002-4990-556X FU One Mind; Department of Veterans Affairs (DVA) [1I01CX000748-01A1, I01CX000120-01]; Mid-Atlantic Mental Illness, Research, and Education Center; NIH (NIMH); HHMI; Burroughs Wellcome Fund; Brain and Behavior Fund; ProMedica Klarman Family Foundation ANGI Welcome Trust Strategic Awards Committee (London); US Department of Veterans Affairs; NIH; Thome Memorial Foundation; American Foundation for Suicide Prevention; Schering Plough Pharmaceuticals; NARSAD [YI 19233]; Conquer Cancer Foundation; NIH [MH085806, MH088609, DK100392, MD009064] FX This study is supported by One Mind. Dr Morey was supported by Department of Veterans Affairs (DVA) 1I01CX000748-01A1 and I01CX000120-01 and the Mid-Atlantic Mental Illness, Research, and Education Center. MBS: Consultant: Care Management Technologies; Janssen, Pfizer, and Tonix Pharmaceuticals Editorial Work: Up-To-Date; Biological Psychiatry (journal); Depression and Anxiety (journal). Dr KJR currently receives funding from NIH (NIMH) and HHMI. In the past, he has received funding from the Burroughs Wellcome Fund, and the Brain and Behavior Fund. He is a founding member of Extinction Pharmaceuticals/Therapade Technologies to develop D-cycloserine, a generically available compound, for use to augment the effectiveness of psychotherapy. He has received no equity or income from this relationship within the last 5 years. JWS has received funding from ProMedica Klarman Family Foundation ANGI Welcome Trust Strategic Awards Committee (London). In the past 3 years, MWL has received funding from the US Department of Veterans Affairs, the NIH, and the Thome Memorial Foundation. Dr AKS receives or has received research support from the American Foundation for Suicide Prevention, Schering Plough Pharmaceuticals, NARSAD (YI 19233), the Conquer Cancer Foundation and NIH (MH085806, MH088609, DK100392 and MD009064). The remaining authors declare no conflict of interest. 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 82 TC 18 Z9 18 U1 3 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2015 VL 40 IS 10 BP 2287 EP 2297 DI 10.1038/npp.2015.118 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CO9KE UT WOS:000359493700001 PM 25904361 ER PT J AU Hill, AS Sahay, A Hen, R AF Hill, Alexis S. Sahay, Amar Hen, Rene TI Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID DENTATE GYRUS; ANTIDEPRESSANT TREATMENT; PARAVENTRICULAR NUCLEUS; DORSOVENTRAL AXIS; ENERGY-BALANCE; NEURONS; STRESS; RAT; HYPOTHALAMUS; EXPRESSION AB Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects. C1 [Hill, Alexis S.; Hen, Rene] Columbia Univ, Dept Neurosci, New York, NY USA. [Sahay, Amar] Massachusetts Gen Hosp, Dept Psychiat, Ctr Regenerat Med, Boston, MA 02114 USA. [Sahay, Amar] Harvard Stem Cell Inst, Boston, MA USA. [Sahay, Amar] Harvard Univ, Sch Med, Boston, MA USA. [Hen, Rene] Columbia Univ, Dept Psychiat, New York, NY USA. [Hen, Rene] Columbia Univ, Dept Pharmacol, New York, NY USA. [Hen, Rene] New York State Psychiat Inst & Hosp, Div Integrat Neurosci, New York, NY 10032 USA. RP Sahay, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Regenerat Med, 185 Cambridge St,CPZN Room 4242, Boston, MA 02114 USA. EM asahay@mgh.harvard.edu; rh95@columbia.edu FU US National Institute of Health [R37MH068542]; National Institute of Aging [R01AG043688]; Hope for Depression Research Foundation (HDRF); New York State Stem Cell Science (NYSTEM) [CO26430]; US National Institutes of Health [1-R01MH104175]; Ellison Medical Foundation New Scholar in Aging; Whitehall Foundation grant FX RH is supported by a US National Institute of Health grant R37MH068542, the National Institute of Aging grant R01AG043688, the Hope for Depression Research Foundation (HDRF), and the New York State Stem Cell Science (NYSTEM) contract CO26430. RH also receives compensation as a consultant for Lundbeck and Servier. AS is supported by a US National Institutes of Health grant 1-R01MH104175, the Ellison Medical Foundation New Scholar in Aging, and a Whitehall Foundation grant. AS is also a consultant for Psybrain LLC. ASH declares no conflict of interest. NR 48 TC 38 Z9 41 U1 7 U2 35 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2015 VL 40 IS 10 BP 2368 EP 2378 DI 10.1038/npp.2015.85 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CO9KE UT WOS:000359493700009 PM 25833129 ER PT J AU Aviki, EM Batalden, RP del Carmen, MG Berkowitz, LR AF Aviki, Emeline M. Batalden, Rebecca Posthuma del Carmen, Marcela G. Berkowitz, Lori R. TI Vacuum-Assisted Closure for Episiotomy Dehiscence SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID THERAPY AB BACKGROUND:Episiotomy dehiscence can result in a large vulvovaginal defect not amenable to delayed primary closure.CASE:A 26-year-old woman who underwent a forceps-assisted vaginal delivery with mediolateral episiotomy presented on postpartum day 5 with complete wound breakdown. Surgical exploration of the wound revealed a defect extending from the perineum into the vagina and deep into the ischiorectal fossa with poor tissue quality not amenable to a timely delayed primary closure. A vacuum-assisted closure device was used in lieu of traditional wound preparation and resulted in wound closure after 11 days of vacuum-assisted wound therapy.CONCLUSION:A vacuum-assisted closure device may be appropriate in cases of complex episiotomy breakdown and may expedite wound healing in the outpatient setting. C1 [Aviki, Emeline M.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Aviki, EM (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. EM eaviki@partners.org NR 8 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2015 VL 126 IS 3 BP 530 EP 533 DI 10.1097/AOG.0000000000000785 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CP2KH UT WOS:000359705400012 PM 25923027 ER PT J AU McCleery, A Green, MF Hellemann, GS Baade, LE Gold, JM Keefe, RSE Kern, RS Mesholam-Gately, RI Seidman, LJ Subotnik, KL Ventura, J Nuechterlein, KH AF McCleery, A. Green, M. F. Hellemann, G. S. Baade, L. E. Gold, J. M. Keefe, R. S. E. Kern, R. S. Mesholam-Gately, R. I. Seidman, L. J. Subotnik, K. L. Ventura, J. Nuechterlein, K. H. TI Latent structure of cognition in schizophrenia: a confirmatory factor analysis of the MATRICS Consensus Cognitive Battery (MCCB) SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Confirmatory factor analysis; MCCB; neurocognition; schizophrenia ID SOCIAL COGNITION; 1ST-EPISODE SCHIZOPHRENIA; NEGATIVE SYMPTOMS; BIPOLAR DISORDER; HEALTHY CONTROLS; 6-FACTOR MODEL; WAIS-III; NEUROCOGNITION; IDENTIFICATION; PERFORMANCE AB Background The number of separable cognitive dimensions in schizophrenia has been debated. Guided by the extant factor analytic literature, the NIMH Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative selected seven cognitive domains relevant to treatment studies in schizophrenia: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. These domains are assessed in the MATRICS Consensus Cognitive Battery (MCCB). The aim of this study was to conduct a confirmatory factor analysis (CFA) of the beta battery of the MCCB to compare the fit of the MATRICS consensus seven-domain model to other models in the current literature on cognition in schizophrenia. Method Using data from 281 schizophrenia outpatients, we compared the seven correlated factors model with alternative models. Specifically, we compared the 7-factor model to (a) a single-factor model, (b) a three correlated factors model including speed of processing, working memory, and general cognition, and (c) a hierarchical model in which seven first-order factors loaded onto a second-order general cognitive factor. Results Multiple fit indices indicated the seven correlated factors model was the best fit for the data and provided significant improvement in model fit beyond the comparison models. Conclusions These results support the assessment of these seven cognitive dimensions in clinical trials of interventions to improve cognition in schizophrenia. Because these cognitive factors are separable to some degree, it is plausible that specific interventions may have differential effects on the domains. C1 [McCleery, A.; Green, M. F.; Hellemann, G. S.; Keefe, R. S. E.; Subotnik, K. L.; Ventura, J.; Nuechterlein, K. H.] David Geffen Sch Med UCLA, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. [Green, M. F.; Kern, R. S.] VISN 22 Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Los Angeles, CA USA. [Baade, L. E.] Univ Kansas, Sch Med, Wichita, KS 67214 USA. [Gold, J. M.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Keefe, R. S. E.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Mesholam-Gately, R. I.; Seidman, L. J.] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr,Dept Psychiat, Publ Psychiat Div,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Seidman, L. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nuechterlein, K. H.] UCLA Dept Psychol, Los Angeles, CA USA. RP McCleery, A (reprint author), David Geffen Sch Med, UCLA Semel Inst Neurosci & Human Behav, Dept Psychiat, 300 Med Plaza,Room 2213, Los Angeles, CA 90095 USA. EM amccleery@mednet.ucla.edu RI McCleery, Amanda/D-5471-2016 OI McCleery, Amanda/0000-0003-2714-6897 FU Canadian Institutes of Health Research [MFE-120919]; NIMH [MH037705, MH066286, N01MH22006] FX A. McCleery is supported by the Canadian Institutes of Health Research fellowship award (MFE-120919). This work was supported by NIMH research grant MH037705 (K. H. Nuechterlein, PI), Center grant MH066286 (K. H. Nuechterlein, PI), and Contract N01MH22006 (S. Marder, PI; M. F. Green, Co-PI; W. Fenton, Project Officer). We thank the patient participants for their help with this study. We gratefully acknowledge the assistance of MATRICS PASS staff and UCLA Aftercare Research Program research assistants and clinical staff. NR 49 TC 3 Z9 3 U1 1 U2 7 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 SEP PY 2015 VL 45 IS 12 BP 2657 EP 2666 DI 10.1017/S0033291715000641 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CO6TV UT WOS:000359290100017 PM 25916421 ER PT J AU Wu, JX Dawes, AJ Sacks, GD Brunicardi, FC Keeler, EB AF Wu, James X. Dawes, Aaron J. Sacks, Greg D. Brunicardi, F. Charles Keeler, Emmett B. TI Cost effectiveness of nonoperative management versus laparoscopic appendectomy for acute uncomplicated appendicitis SO SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; PERFORATED APPENDICITIS; ANTIBIOTIC-TREATMENT; CLAVULANIC-ACID; METAANALYSIS; THERAPY; SURGERY; OUTCOMES; DIVERTICULITIS AB Background. Appendectomy remains the gold standard in the treatment of acute, uncomplicated appendicitis in the United States. Nonetheless, there is growing evidence that nonoperative management is safe and efficacious. Methods. We constructed a decision tree to compare nonoperative management of appendicitis with laparoscopic appendectomy in otherwise healthy adults. Model variables were abstracted from a literature review, data from the Healthcare Cost and Utilization Project data, the Medicare Physician Fee schedule, and the American College of Surgeons Surgical Risk Calculator. Uncertainty surrounding parameters of the model was assessed via 1-way and probabilistic sensitivity analyses. Results. Operative management cost $12,213 per patient. Nonoperative management without interval appendectomy (IA) was the dominant strategy, costing $1,865 less and producing 0.03 more quality-adjusted life-years (QALYs). Nonoperative management with IA cost $4,271 more than operative management, but yielded only 0.01 additional QALY. One-way sensitivity analysis suggested operative management would become the preferred strategy if the recurrence rate was >40.5% or the total cost of appendectomy was decreased to <$5,468. Probabilistic sensitivity analysis confirmed nonoperative management without IA was the preferred strategy in 95.6% of cases. Conclusion. Nonoperative management without IA is the least costly, most effective treatment for acute, uncomplicated appendicitis and warrants further evaluation in a disease thought to be definitively surgical. C1 [Wu, James X.; Dawes, Aaron J.; Sacks, Greg D.; Brunicardi, F. Charles] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Sacks, Greg D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dawes, Aaron J.; Sacks, Greg D.; Keeler, Emmett B.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Keeler, Emmett B.] RAND Corp, Santa Monica, CA USA. RP Wu, JX (reprint author), 757 Westwood Blvd,Mail Room B711, Los Angeles, CA 90095 USA. EM JamesWu@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 FU Robert Wood Johnson Foundation; VA Office of Academic Affiliations; H. H. Lee Research Award FX This work was supported by the Robert Wood Johnson Foundation Clinical Scholars Program (Dr Dawes, Dr Sacks), VA Office of Academic Affiliations (Dr Dawes), and H. H. Lee Research Award (Dr James Wu). NR 39 TC 3 Z9 3 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2015 VL 158 IS 3 BP 712 EP 721 DI 10.1016/j.surg.2015.06.021 PG 10 WC Surgery SC Surgery GA CP3CS UT WOS:000359755000017 PM 26195106 ER PT J AU Esquivel, MM Molina, G Uribe-Leitz, T Lipsitz, SR Rose, J Bickler, S Gawande, AA Haynes, AB Weiser, TG AF Esquivel, Micaela M. Molina, George Uribe-Leitz, Tarsicio Lipsitz, Stuart R. Rose, John Bickler, Stephen Gawande, Atul A. Haynes, Alex B. Weiser, Thomas G. TI Proposed Minimum Rates of Surgery to Support Desirable Health Outcomes: An Observational Study Based on Three Strategies SO WORLD JOURNAL OF SURGERY LA English DT Article ID GLOBAL HEALTH AB Background The global volume of surgery is estimated at 312.9 million operations annually, but rates of surgery vary dramatically. Identifying surgical rates associated with improved health outcomes would be useful for benchmarking and targeted health system strengthening. Methods We identified rates of surgery associated with a life expectancy (LE) of 74-75 years, a maternal mortality ratio (MMR) of less than or equal to 100 per 100,000 live births, and the estimated need for surgery in the seven global burden of disease (GBD) super-regions based on the prevalence of surgical conditions. We compared our findings to surgical rates from Chile, China, Costa Rica, and Cuba ("4C"), countries with moderate resources but high health outcomes. Results The median surgical rates associated with LE of 74-75 years (N = 17) and MMR below 100 (N = 109) are 4392 (IQR 2897-4873) and 5028 (IQR 4139-6778) operations per 100,000 people annually, respectively. The mean surgical rate estimated for the seven super-regions was 4723 (95 % CI 3967-5478) operations per 100,000 people annually. The "4C" countries had a mean surgical rate of 4344 (95 % CI 2620-6068) operations per 100,000 people annually. Thirteen of the twenty-one GBD regions, accounting for 78 % of the world's population, do not achieve rates of surgery at the lowest end of this range. Conclusions We identified a narrow range of surgical rates associated with important health indicators. This target range can be used for benchmarking of surgical services, and as part of a policy aimed at strengthening health care systems and surgical capacity. C1 [Esquivel, Micaela M.; Uribe-Leitz, Tarsicio; Weiser, Thomas G.] Stanford Univ, Med Ctr, Dept Surg, Stanford, CA 94305 USA. [Molina, George; Lipsitz, Stuart R.; Gawande, Atul A.; Haynes, Alex B.] Brigham & Womens Hosp, Ariadne Labs, Boston, MA 02215 USA. [Molina, George; Lipsitz, Stuart R.; Gawande, Atul A.; Haynes, Alex B.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02215 USA. [Molina, George; Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Rose, John; Bickler, Stephen] Univ Calif San Diego, Div Pediat Surg, Rady Childrens Hosp, San Diego, CA 92105 USA. [Rose, John] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Esquivel, MM (reprint author), Stanford Univ, Med Ctr, Dept Surg, 300 Pasteur Dr,S067,H-3691, Stanford, CA 94305 USA. EM mesquive@stanford.edu NR 17 TC 4 Z9 4 U1 1 U2 1 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 SEP PY 2015 VL 39 IS 9 BP 2126 EP 2131 DI 10.1007/s00268-015-3092-7 PG 6 WC Surgery SC Surgery GA CO8UO UT WOS:000359447800004 PM 25968342 ER PT J AU Chao, TE Patel, PB Kikubaire, M Niescierenko, M Hagander, L Meara, JG AF Chao, Tiffany E. Patel, Pratik B. Kikubaire, Michael Niescierenko, Michelle Hagander, Lars Meara, John G. TI Surgical Care in Liberia and Implications for Capacity Building SO WORLD JOURNAL OF SURGERY LA English DT Article ID SUB-SAHARAN AFRICA; GLOBAL HEALTH; SURGERY; COUNTRIES AB Situational needs of health care facilities inform the optimal allocation of resources and quality improvement efforts. This study examines surgical care delivery metrics at a tertiary care institution in Liberia. We retrospectively reviewed operative and ward logbooks from January 1 to December 31, 2012. Data parameters included patients' age, diagnosis, procedure, mortality, and perioperative provider information. In 2012, 1,036 operations were performed. The breakdown of adult surgical cases reveals 452 (45.1 %) general surgery operations, 192 (18.5 %) orthopedic operations, and 180 (17.4 %) ophthalmic operations. Other significant case volume included urologic 53 (5.1 %), ENT 36 (3.5 %), neurosurgical 31 (3.0 %), vascular 24 (2.3 %), and plastic 14 (1.4 %) operations. Pediatric patients accounted for 24.5 % (243) of surgical cases, and 9 % of pediatric surgical cases were for hydrocephalus. General, spinal, and total intravenous anesthesia was provided by non-physician personnel, except when surgeons provided their own anesthesia. Ward logs documented 7.4 % mortality among all patients admitted to the surgical ward, most of which occurred after exploratory laparotomy (44 %), in burn (14 %) patients, and in patients with head/neck emergencies (12 %). This operative log review can be used to identify surgical practice patterns, needs, and deficits in order to inform the growth of surgical capacity at Liberia's only tertiary medical institution. Using this data to identify critical areas of high-yield operations (e.g., for pediatric hydrocephalus), or excessively high mortality rates (e.g., in burn care), can focus the direction of limited resources toward areas of need. While the heavy reliance on non-consultant surgeons reflects human capacity shortages and a pressing need for postgraduate training programs, identifying the breadth of surgical expertise demonstrated in these operative logs reveals the proficiencies required of surgeons to provide comprehensive surgical care in this setting. C1 [Chao, Tiffany E.; Patel, Pratik B.; Hagander, Lars; Meara, John G.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA USA. [Chao, Tiffany E.; Patel, Pratik B.; Hagander, Lars; Meara, John G.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. [Chao, Tiffany E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. [Kikubaire, Michael] John F Kennedy Med Ctr, Dept Surg, Monrovia, Liberia. [Niescierenko, Michelle] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Hagander, Lars] Lund Childrens Hosp, Dept Pediat Surg, Lund, Sweden. [Hagander, Lars] Lund Univ, Fac Med, Dept Clin Sci Lund, Int Pediat, Lund, Sweden. RP Chao, TE (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02115 USA. EM tchao@partners.org FU Boston Children's Hospital Department of Plastic Oral Surgery; Massachusetts General Hospital Global Health Center of Expertise FX The authors acknowledge editorial and logistical support from Dr. Vuyu Kanda Golakai, Professor of Surgery and Dean of A.M. Dogliotti College of Medicine of the University of Liberia. They also appreciate support from the administration, surgical, and operating theater staff of JFK Medical Center. Funding support is from Boston Children's Hospital Department of Plastic & Oral Surgery and Massachusetts General Hospital Global Health Center of Expertise. NR 17 TC 1 Z9 1 U1 0 U2 1 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 SEP PY 2015 VL 39 IS 9 BP 2140 EP 2146 DI 10.1007/s00268-014-2905-4 PG 7 WC Surgery SC Surgery GA CO8UO UT WOS:000359447800006 PM 25446492 ER PT J AU Burke, T Manglani, Y Altawil, Z Dickson, A Clark, R Okelo, S Ahn, R AF Burke, Thomas Manglani, Yogeeta Altawil, Zaid Dickson, Alexandra Clark, Rachel Okelo, Stephen Ahn, Roy TI A Safe-Anesthesia Innovation for Emergency and Life-Improving Surgeries When no Anesthetist is Available: A Descriptive Review of 193 Consecutive Surgeries SO WORLD JOURNAL OF SURGERY LA English DT Article ID PROCEDURAL SEDATION; KETAMINE; COUNTRIES; ANALGESIA AB The worldwide human resource gap in anesthesia services often presents a barrier to accessing life-saving and life-improving surgeries. This paper assessed the impact of a ketamine anesthesia package, Every Second Matters-Ketamine (ESM-Ketamine)(TM), for use in emergency and life-improving surgeries by non-anesthetist clinicians in a resource-limited setting when no anesthetist was available. We analyzed prospectively collected data from 193 surgeries constituting a pilot implementation of the ESM-Ketamine package, among three sub-district hospitals in Western Kenya. The study population comprises patients who required emergency or life-improving surgery when no anesthetist was available. Non-anesthetist clinicians in three sub-district hospitals underwent a 5-day training course in ESM-Ketamine complemented by checklists and an ESM-Ketamine Kit. Data were collected prospectively every time the ESM-Ketamine pathway was invoked. The training cases, although primarily tubal ligations, were included. The primary outcome measures centered on capturing the ability to safely support emergency and life-improving surgeries, when no anesthetist was available, through invoking the ESM-Ketamine pathway. The registry was critically examined using standard descriptive and frequency analysis. 193 surgical procedures were supported using the ESM-Ketamine package by five ESM-Ketamine trained providers. Brief (< 30 s) patient desaturation below 92 % and hallucinations occurred in 16 out of 186 (8.6 %) and 23 out of 190 patients (12.1 %), respectively. There were no reported major adverse events such as death, prolonged desaturations (over 30 s), or injury resulting from ketamine use. This study provides promising initial evidence that the ESM-Ketamine package can support emergency and life-improving surgeries in resource-limited settings when no anesthetist is available. C1 [Burke, Thomas; Manglani, Yogeeta; Altawil, Zaid; Dickson, Alexandra; Clark, Rachel; Ahn, Roy] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Dept Emergency Med, Boston, MA 02114 USA. [Burke, Thomas; Ahn, Roy] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Okelo, Stephen] Maseno Univ, Sch Med, Dept Anesthesia, Maseno, Kenya. RP Burke, T (reprint author), Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Dept Emergency Med, Zero Emerson Pl,Suite 104, Boston, MA 02114 USA. EM tfburke@partners.org FU Ujenzi Charitable Trust; United States Agency for International Development (USAID); Government of Norway; Bill & Melinda Gates Foundation; Grand Challenges Canada; UK Government FX We acknowledge the assistance of Kristina Tester, Emily de Redon, Javan Imbamba, Stella Odenyo, and Drs. Brett D. Nelson, Melody Eckardt, Debora Rogo, Svjetlana Lozo, Vikram Palanivel, and Walter Obita. Grant support for the research reported: The Every Second Matters- Ketamine (ESM-Ketamine) is made possible through the generous support of the Ujenzi Charitable Trust, the Saving Lives at Birth partners: the United States Agency for International Development (USAID), the Government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada, and the UK Government. This manuscript was prepared by MGH and does not necessarily reflect the views of the funding partners. NR 20 TC 5 Z9 5 U1 0 U2 4 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 SEP PY 2015 VL 39 IS 9 BP 2147 EP 2152 DI 10.1007/s00268-015-3118-1 PG 6 WC Surgery SC Surgery GA CO8UO UT WOS:000359447800007 PM 26067637 ER PT J AU Uribe-Leitz, T Esquivel, MM Molina, G Lipsitz, SR Verguet, S Rose, J Bickler, SW Gawande, AA Haynes, AB Weiser, TG AF Uribe-Leitz, Tarsicio Esquivel, Micaela M. Molina, George Lipsitz, Stuart R. Verguet, Stephane Rose, John Bickler, Stephen W. Gawande, Atul A. Haynes, Alex B. Weiser, Thomas G. TI Projections for Achieving the Lancet Commission Recommended Surgical Rate of 5000 Operations per 100,000 Population by Region-Specific Surgical Rate Estimates SO WORLD JOURNAL OF SURGERY LA English DT Article ID GLOBAL HEALTH; SURGERY AB We previously identified a range of 4344-5028 annual operations per 100,000 people to be related to desirable health outcomes. From this and other evidence, the Lancet Commission on Global Surgery recommends a minimum rate of 5000 operations per 100,000 people. We evaluate rates of growth and estimate the time it will take to reach this minimum surgical rate threshold. We aggregated country-level surgical rate estimates from 2004 to 2012 into the twenty-one Global Burden of Disease (GBD) regions. We calculated mean rates of surgery proportional to population size for each year and assessed the rate of growth over time. We then extrapolated the time it will take each region to reach a surgical rate of 5000 operations per 100,000 population based on linear rates of change. All but two regions experienced growth in their surgical rates during the past 8 years. Fourteen regions did not meet the recommended threshold in 2012. If surgical capacity continues to grow at current rates, seven regions will not meet the threshold by 2035. Eastern Sub-Saharan Africa will not reach the recommended threshold until 2124. The rates of growth in surgical service delivery are exceedingly variable. At current rates of surgical and population growth, 6.2 billion people (73 % of the world's population) will be living in countries below the minimum recommended rate of surgical care in 2035. A strategy for strengthening surgical capacity is essential if these targets are to be met in a timely fashion as part of the integrated health system development. C1 [Uribe-Leitz, Tarsicio; Esquivel, Micaela M.; Weiser, Thomas G.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. [Molina, George; Lipsitz, Stuart R.; Gawande, Atul A.; Haynes, Alex B.] Brigham & Womens Hosp, Ariadne Labs, Boston, MA 02215 USA. [Molina, George; Lipsitz, Stuart R.; Gawande, Atul A.; Haynes, Alex B.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02215 USA. [Molina, George; Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Verguet, Stephane] Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Rose, John] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Rose, John; Bickler, Stephen W.] Univ Calif San Diego, Div Pediat Surg, Rady Childrens Hosp, San Diego, CA 92123 USA. RP Uribe-Leitz, T (reprint author), Stanford Univ, Sch Med, Dept Surg, 300 Pasteur Dr, Stanford, CA 94305 USA. EM pturibe@stanford.edu OI Uribe-Leitz, Tarsicio/0000-0003-2616-476X NR 14 TC 1 Z9 1 U1 1 U2 4 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 SEP PY 2015 VL 39 IS 9 BP 2168 EP 2172 DI 10.1007/s00268-015-3113-6 PG 5 WC Surgery SC Surgery GA CO8UO UT WOS:000359447800010 PM 26067635 ER PT J AU Tan, TC Hung, JW AF Tan, Timothy C. Hung, Judy W. TI Standard transthoracic echocardiography and transesophageal echocardiography views of mitral pathology that every surgeon should know SO ANNALS OF CARDIOTHORACIC SURGERY LA English DT Article DE Mitral valve; echocardiography; surgery; mitral stenosis (MS); mitral regurgitation (MR) ID CUTTING 2ND-ORDER CHORDAE; VALVE-PROLAPSE; 3-DIMENSIONAL ECHOCARDIOGRAPHY; REGURGITATION; LEAFLET; STENOSIS; ANTERIOR; REPAIR; DISEASE; DIAGNOSIS AB The mitral valve is the most commonly diseased heart valve and the prevalence of mitral valve disease increases proportionally with age. Echocardiography is the primary diagnostic imaging modality used in the assessment of patients with mitral valve disease. It is a noninvasive method which provides accurate anatomic and functional information regarding the mitral valve and can identify the mechanism of mitral valve pathology. This is especially useful as it may guide surgical repair. This is increasingly relevant given the growing trend of patients undergoing mitral valve repair. Collaboration between cardiac surgeons and echocardiographers is critical in the evaluation of mitral valve disease and for identification of complex valvular lesions that require advanced surgical skill to repair. This article will provide an overview of transthoracic and transesophageal assessment of common mitral valve pathology that aims to aid surgical decision making. C1 [Hung, Judy W.] Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02114 USA. RP Hung, JW (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM jhung@mgh.harvard.edu NR 48 TC 1 Z9 1 U1 0 U2 2 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2225-319X EI 2304-1021 J9 ANN CARDIOTHORAC SUR JI Ann. Cardiothorac. Surg. PD SEP PY 2015 VL 4 IS 5 BP 449 EP 460 DI 10.3978/j.issn.2225-319X.2015.03.05 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW0TG UT WOS:000383355000008 PM 26539350 ER PT J AU Arvizu, M Tanrikut, C Hauser, R Keller, M Chavarro, JE AF Arvizu, M. Tanrikut, C. Hauser, R. Keller, M. Chavarro, J. E. TI MALE DIETARY TRANS FAT INTAKE IS INVERSELY ASSOCIATED TO FERTILIZATION RATES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Arvizu, M.] Harvard TH Chan Sch Publ Hlth, Nutr, Boston, MA USA. [Tanrikut, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hauser, R.; Keller, M.; Chavarro, J. E.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-271 BP E103 EP E104 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900269 ER PT J AU Christianson, MS Legro, R Jin, S Eisenberg, E Diamond, MP Hansen, KR Vitek, W Styer, AK Casson, PR Coutifaris, C Christman, GM Alvero, R Puscheck, EE Christy, A Zhang, H Polotsky, AJ Santoro, N AF Christianson, M. S. Legro, R. Jin, S. Eisenberg, E. Diamond, M. P. Hansen, K. R. Vitek, W. Styer, A. K. Casson, P. R. Coutifaris, C. Christman, G. M. Alvero, R. Puscheck, E. E. Christy, A. Zhang, H. Polotsky, A. J. Santoro, N. TI UTILITY OF SONOHYSTEROGRAPHY FOR TUBAL PATENCY ASSESSMENT IN THE PREGNANCY IN POLYCYSTIC OVARY SYNDROME II TRIAL SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Christianson, M. S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Legro, R.] Penn State Univ, Coll Med, University Pk, PA 16802 USA. [Jin, S.; Zhang, H.] Yale Sch Publ Hlth, New Haven, CT USA. [Eisenberg, E.] NICHD, Bethesda, MD USA. [Diamond, M. P.] Georgia Regents Univ, Augusta, GA USA. [Hansen, K. R.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Vitek, W.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Styer, A. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Casson, P. R.] Northeastern Reprod Med, Colchester, VT USA. [Coutifaris, C.] Univ Penn, Philadelphia, PA 19104 USA. [Christman, G. M.] Univ Florida, Sch Med, Gainesville, FL USA. [Alvero, R.; Polotsky, A. J.; Santoro, N.] Univ Colorado, Aurora, CO USA. [Puscheck, E. E.] Wayne State Univ, Sch Med, Detroit, MI USA. [Christy, A.] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-258 BP E98 EP E99 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900256 ER PT J AU Dimitriadis, I Murtadi, G Toth, TL Souter, I AF Dimitriadis, I. Murtadi, G. Toth, T. L. Souter, I. TI DOES PATERNAL AGE HAVE AN EFFECT ON TOTAL MOTILE SPERM COUNTS (TMC) AND THE OUTCOME OF OVULATION INDUCTION/INTRAUTERINE INSEMINATION (OI/IUI) CYCLES? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Dimitriadis, I.] Tufts Med Ctr, Boston, MA USA. [Murtadi, G.] Massachusetts Gen Hosp, Fertil Ctr, Boston, MA 02114 USA. [Toth, T. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Souter, I.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-200 BP E77 EP E77 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900199 ER PT J AU Gaskins, AJ Rich-Edwards, JW Williams, P Toth, T Missmer, SA Chavarro, JE AF Gaskins, A. J. Rich-Edwards, J. W. Williams, P. Toth, T. Missmer, S. A. Chavarro, J. E. TI PRE-PREGNANCY LOW TO MODERATE ALCOHOL INTAKE AND RISK OF SPONTANEOUS ABORTION. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Gaskins, A. J.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Rich-Edwards, J. W.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Rich-Edwards, J. W.; Missmer, S. A.] Harvard Med Sch, Boston, MA USA. [Williams, P.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Toth, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Missmer, S. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chavarro, J. E.] Harvard Sch Publ Hlth, Boston, MA USA. NR 0 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-703 BP E348 EP E348 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900948 ER PT J AU Hansen, KR He, AW Styer, AK Butts, S Engmann, L AF Hansen, K. R. He, A. W. Styer, A. K. Butts, S. Engmann, L. CA T NICHD's Reprod Med Network TI PREDICTORS OF PREGNANCY AND LIVE-BIRTH IN COUPLES WITH UNEXPLAINED INFERTILITY FOLLOWING SUPEROVULATION-INTRAUTERINE INSEMINATION SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Hansen, K. R.] Univ Oklahoma, Hlth Sci Ctr, Obstet & Gynecol, Oklahoma City, OK USA. [He, A. W.] Yale Univ, Sch Publ Hlth, Biostat, New Haven, CT USA. [Styer, A. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Butts, S.] Univ Penn, Obstet & Gynecol, Philadelphia, PA 19104 USA. [Engmann, L.] Univ Connecticut, Ctr Hlth, Obstet & Gynecol, Farmington, CT USA. [T NICHD's Reprod Med Network] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-255 BP E97 EP E98 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900253 ER PT J AU Hayden, RP Tanrikut, C AF Hayden, R. P. Tanrikut, C. TI HYDRODYNAMICS OF THE HUMAN GONADAL VEIN: A FINITE ELEMENT MODEL TO EXPLORE ELEVATED LEFT TESTICULAR VENOUS PRESSURES RELATED TO VARICOCELE SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Hayden, R. P.; Tanrikut, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-207 BP E80 EP E80 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900205 ER PT J AU Lange, A Karmon, AE Murtadi, G Souter, I Petrozza, JC AF Lange, A. Karmon, A. E. Murtadi, G. Souter, I. Petrozza, J. C. TI THE UTILITY AND FEASIBILITY OF USING THE INTERNET FOR ENROLLING AND FOLLOWING WOMEN TO ASSESS FECUNDITY SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Lange, A.; Murtadi, G.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Karmon, A. E.; Petrozza, J. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Souter, I.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-34 BP E117 EP E118 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900306 ER PT J AU Lange, A Carignan, CC Minguez-Alarcon, L Williams, P Calafat, AM Toth, TL Hauser, R AF Lange, A. Carignan, C. C. Minguez-Alarcon, L. Williams, P. Calafat, A. M. Toth, T. L. Hauser, R. TI TRICLOSAN EXPOSURE AND TREATMENT OUTCOMES IN WOMEN UNDERGOING IN VITRO FERTILIZATION SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Lange, A.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Carignan, C. C.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Minguez-Alarcon, L.; Williams, P.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Calafat, A. M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Toth, T. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hauser, R.] Harvard Chan Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-223 BP E86 EP E86 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900221 ER PT J AU Lee, MS Evans, BT Hornstein, MD AF Lee, M. S. Evans, B. T. Hornstein, M. D. TI ECONOMIC IMPLICATIONS OF THE SART GUIDELINES ON EMBRYO TRANSFER: HEALTHCARE DOLLARS SAVED BY REDUCING IATROGENIC TRIPLETS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Lee, M. S.; Hornstein, M. D.] Brigham & Womens Hosp, Obstet & Gynecol, Boston, MA 02115 USA. [Lee, M. S.; Evans, B. T.; Hornstein, M. D.] Harvard Med Sch, Boston, MA USA. [Evans, B. T.] Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-666 BP E335 EP E336 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900911 ER PT J AU Lee, MS Cardozo, ER Karmon, AE Wright, DL Toth, T AF Lee, M. S. Cardozo, E. R. Karmon, A. E. Wright, D. L. Toth, T. TI THE IMPACT OF TRANSFER TIME ON CLINICAL PREGNANCY IN FROZEN EMBRYO TRANSFER CYCLES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Lee, M. S.; Cardozo, E. R.; Karmon, A. E.; Wright, D. L.; Toth, T.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-150 BP E59 EP E59 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900150 ER PT J AU Messerlian, C Wylie, B Williams, P Ford, JB Keller, M Calafat, AM Hauser, R AF Messerlian, C. Wylie, B. Williams, P. Ford, J. B. Keller, M. Calafat, A. M. Hauser, R. TI URINARY PHTHALATE METABOLITE CONCENTRATIONS WERE ASSOCIATED WITH PREGNANCY LOSS AMONG WOMEN CONCEIVING WITH MEDICALLY ASSISTED REPRODUCTION SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Messerlian, C.; Ford, J. B.; Keller, M.; Hauser, R.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Wylie, B.; Hauser, R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Williams, P.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Calafat, A. M.] Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-96 BP E38 EP E38 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900096 ER PT J AU Stern, JE Gopal, D Kotelchuck, M Luke, B AF Stern, J. E. Gopal, D. Kotelchuck, M. Luke, B. TI VALIDATION OF BIRTH DEFECTS DATA IN THE SART CORS TO BIRTH DEFECTS REGISTRY DATA IN MASSACHUSETTS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Stern, J. E.] Geisel Sch Med Dartmouth, Obstet & Gynecol, Lebanon, NH USA. [Gopal, D.] BUSPH, Boston, MA USA. [Kotelchuck, M.] MassGen Hosp Children, Boston, MA USA. [Luke, B.] Michigan State Univ, E Lansing, MI 48824 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-292 BP E205 EP E206 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900551 ER PT J AU Styer, AK Christianson, MS Vitek, W Baker, V Santoro, N Armstrong, A Polotsky, AJ Luke, B AF Styer, A. K. Christianson, M. S. Vitek, W. Baker, V. Santoro, N. Armstrong, A. Polotsky, A. J. Luke, B. TI FACTORS ASSOCIATED WITH ELECTIVE SINGLE EMBRYO TRANSFER (ESET) UTILIZATION IN THE UNITED STATES: A NATIONAL STUDY SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Styer, A. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Christianson, M. S.] Johns Hopkins Univ, Sch Med, Lutherville Timonium, MD USA. [Vitek, W.] Univ Rochester, Sch Med, Rochester, NY USA. [Baker, V.] Stanford Univ, Palo Alto, CA 94304 USA. [Santoro, N.; Polotsky, A. J.] Univ Colorado, Aurora, CO USA. [Armstrong, A.] NICHD, Bethesda, MD USA. [Luke, B.] Research, Ann Arbor, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-268 BP E102 EP E102 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900266 ER PT J AU Styer, AK Vitek, W Christianson, MS Baker, V Armstrong, A Santoro, N Luke, B Polotsky, AJ AF Styer, A. K. Vitek, W. Christianson, M. S. Baker, V. Armstrong, A. Santoro, N. Luke, B. Polotsky, A. J. TI ELECTIVE SINGLE EMBRYO TRANSFER (ESET) IS ASSOCIATED WITH NON-LOW BIRTHWEIGHT TERM SINGLETON OUTCOMES: AN ANALYSIS OF 263,375 CYCLES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Styer, A. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Vitek, W.] Univ Rochester, Sch Med, Rochester, NY USA. [Christianson, M. S.] Johns Hopkins Univ, Sch Med, Lutherville Timonium, MD USA. [Baker, V.] Stanford Univ, Palo Alto, CA 94304 USA. [Armstrong, A.] NICHD, Bethesda, MD USA. [Santoro, N.; Polotsky, A. J.] Univ Colorado, Aurora, CO USA. [Luke, B.] Research, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-39 BP E16 EP E16 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900040 ER PT J AU Tiseo, BC Gaskins, AJ Chavarro, JE Hauser, R Tanrikut, C AF Tiseo, B. C. Gaskins, A. J. Chavarro, J. E. Hauser, R. Tanrikut, C. TI DIETARY COENZYME Q10 INTAKE AND SEMEN PARAMETERS IN A SUBFERTILE POPULATION SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Tiseo, B. C.] Univ Sao Paulo, Hosp Clin, Sch Med, Div Urol, Sao Paulo, Brazil. [Gaskins, A. J.; Chavarro, J. E.; Hauser, R.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Tanrikut, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-209 BP E81 EP E81 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900207 ER PT J AU Tiseo, BC Gabrielsen, J Gaskins, AJ Swan, SH Mendiola, J Joergensen, N Chavarro, JE Tanrikut, C AF Tiseo, B. C. Gabrielsen, J. Gaskins, A. J. Swan, S. H. Mendiola, J. Joergensen, N. Chavarro, J. E. Tanrikut, C. TI RELATION BETWEEN DIETARY IRON INTAKE AND TESTICULAR FUNCTION IN YOUNG MEN SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Tiseo, B. C.] Univ Sao Paulo, Sch Med, Hosp Clin, Div Urol, Sao Paulo, Brazil. [Gabrielsen, J.; Tanrikut, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gaskins, A. J.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Swan, S. H.] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. [Joergensen, N.] Rigshosp, Copenhagen, Denmark. [Chavarro, J. E.] Harvard Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-205 BP E79 EP E80 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900204 ER PT J AU Prigerson, HG Bao, YH Shah, MA Paulk, ME LeBlanc, TW Schneider, BJ Garrido, MM Reid, MC Berlin, DA Adelson, KB Neugut, AI Maciejewski, PK AF Prigerson, Holly G. Bao, Yuhua Shah, Manish A. Paulk, M. Elizabeth LeBlanc, Thomas W. Schneider, Bryan J. Garrido, Melissa M. Reid, M. Carrington Berlin, David A. Adelson, Kerin B. Neugut, Alfred I. Maciejewski, Paul K. TI Chemotherapy Use, Performance Status, and Quality of Life at the End of Life SO JAMA ONCOLOGY LA English DT Article ID METASTATIC BREAST-CANCER; CELL LUNG-CANCER; MEDICARE BENEFICIARIES; PROGNOSTIC FACTORS; CARE; SURVIVAL; MONOTHERAPY; DOCETAXEL; ONCOLOGY; DESIGN AB IMPORTANCE Although many patients with end-stage cancer are offered chemotherapy to improve quality of life (QOL), the association between chemotherapy and QOL amid progressive metastatic disease has not been well-studied. American Society for Clinical Oncology guidelines recommend palliative chemotherapy only for solid tumor patients with good performance status. OBJECTIVE To evaluate the association between chemotherapy use and QOL near death (QOD) as a function of patients' performance status. DESIGN, SETTING, AND PARTICIPANTS A multi-institutional, longitudinal cohort study of patients with end-stage cancer recruited between September 2002 and February 2008. Chemotherapy use (n = 158 [50.6%]) and Eastern Cooperative Oncology Group (ECOG) performance status were assessed at baseline (median = 3.8 months before death) and patients with progressive metastatic cancer (N = 312) following at least 1 chemotherapy regimen were followed prospectively until death at 6 outpatient oncology clinics in the United States. MAIN OUTCOMES AND MEASURES Patient QOD was determined using validated caregiver ratings of patients' physical and mental distress in their final week. RESULTS Chemotherapy use was not associated with patient survival controlling for clinical setting and patients' performance status. Among patients with good (ECOG score = 1) baseline performance status, chemotherapy use compared with nonuse was associated with worse QOD (odds ratio [OR], 0.35; 95% CI, 0.17-0.75; P =.01). Baseline chemotherapy use was not associated with QOD among patients with moderate (ECOG score = 2) baseline performance status (OR, 1.06; 95% CI, 0.51-2.21; P =.87) or poor (ECOG score = 3) baseline performance status (OR, 1.34; 95% CI, 0.46-3.89; P =.59). CONCLUSIONS AND RELEVANCE Although palliative chemotherapy is used to improve QOL for patients with end-stage cancer, its use did not improve QOD for patients with moderate or poor performance status and worsened QOD for patients with good performance status. The QOD in patients with end-stage cancer is not improved, and can be harmed, by chemotherapy use near death, even in patients with good performance status. C1 [Prigerson, Holly G.; Maciejewski, Paul K.] Weill Cornell Med Coll, Ctr Res End Of Life Care, New York, NY USA. [Prigerson, Holly G.; Reid, M. Carrington] Weill Cornell Med Coll, Dept Med, Div Geriatr & Palliat Med, New York, NY USA. [Bao, Yuhua] Weill Cornell Med Coll, Dept Healthcare Policy & Res, New York, NY USA. [Shah, Manish A.] Weill Cornell Med Coll, Meyer Canc Ctr, Med Oncol Solid Tumor Program, New York, NY USA. [LeBlanc, Thomas W.] Duke Univ, Sch Med, Dept Med, Div Hematol Malignancies & Cellular Therapy, Durham, NC 27706 USA. [Paulk, M. Elizabeth] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Schneider, Bryan J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Garrido, Melissa M.] James J Peters VA Med Ctr, Bronx, NY USA. [Garrido, Melissa M.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Berlin, David A.] New York Presbyterian Hosp, Weill Cornell Ctr, Dept Med, Med Intens Care Unit, New York, NY USA. [Neugut, Alfred I.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Neugut, Alfred I.] Columbia Univ, Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Neugut, Alfred I.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Adelson, Kerin B.] Yale Univ, Sch Med, Smilow Canc Hosp Yale New Haven, New Haven, CT USA. [Maciejewski, Paul K.] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. RP Prigerson, HG (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, Ctr Res End Of Life Care, 525 E 68th St,Box 39,1404 Baker Pavil, New York, NY 10065 USA. EM hgp2001@med.cornell.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370]; National Institute of Minority Heath and Health Disparities [MD007652]; Weill Cornell Medical College grant; Health Services Research and Development Service Career Development Award from the Department of Veterans Affairs [11-201/CDP 12-255] FX This research was supported in part by the following grants: MH63892 from the National Institute of Mental Health and CA106370 from the National Cancer Institute (Dr Prigerson); MD007652 from the National Institute of Minority Heath and Health Disparities (Drs Prigerson and Maciejewski); Weill Cornell Medical College grant (Drs Prigerson and Bao); and Health Services Research and Development Service Career Development Award 11-201/CDP 12-255 from the Department of Veterans Affairs (Dr Garrido). NR 31 TC 48 Z9 50 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2015 VL 1 IS 6 BP 778 EP 784 DI 10.1001/jamaoncol.2015.2378 PG 7 WC Oncology SC Oncology GA DW5HO UT WOS:000383674800013 PM 26203912 ER PT J AU Venturini, S Dominici, F Parmigiani, G AF Venturini, Sergio Dominici, Francesca Parmigiani, Giovanni TI Generalized Quantile Treatment Effect: A Flexible Bayesian Approach Using Quantile Ratio Smoothing SO BAYESIAN ANALYSIS LA English DT Article DE average treatment effect (ATE); medical expenditures; National Medical Expenditures Survey (NMES); Q-Q plot; quantile function; quantile treatment effect (QTE); tailweight ID MICRONUTRIENT SUPPLEMENTATION; BIRTH-WEIGHT; MODEL; DISTRIBUTIONS; REGRESSION AB We propose a new general approach for estimating the effect of a binary treatment on a continuous and potentially highly skewed response variable, the generalized quantile treatment effect (GQTE). The GQTE is defined as the difference between a function of the quantiles under the two treatment conditions. As such, it represents a generalization over the standard approaches typically used for estimating a treatment effect (i.e., the average treatment effect and the quantile treatment effect) because it allows the comparison of any arbitrary characteristic of the outcome's distribution under the two treatments. Following Dominici et al. (2005), we assume that a pre-specified transformation of the two quantiles is modeled as a smooth function of the percentiles. This assumption allows us to link the two quantile functions and thus to borrow information from one distribution to the other. The main theoretical contribution we provide is the analytical derivation of a closed form expression for the likelihood of the model. Exploiting this result we propose a novel Bayesian inferential methodology for the GQTE. We show some finite sample properties of our approach through a simulation study which confirms that in some cases it performs better than other nonparametric methods. As an illustration we finally apply our methodology to the 1987 National Medicare Expenditure Survey data to estimate the difference in the single hospitalization medical cost distributions between cases (i.e., subjects affected by smoking attributable diseases) and controls. C1 [Venturini, Sergio] Univ Bocconi, CERGAS, I-20136 Milan, Italy. [Dominici, Francesca; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Venturini, S (reprint author), Univ Bocconi, CERGAS, Via Rontgen 1, I-20136 Milan, Italy. EM sergio.venturini@unibocconi.it; fdominic@hsph.harvard.edu; gp@jimmy.harvard.edu FU NIH/NIEHS [R01ES012054]; EPA [R83622, RD83241701]; HEI [4909-RFA11-1/12-3]; AHRQ [K18 HS021991] FX The research of Dominici was supported by Award Number R01ES012054 (Statistical Methods for Population Health Research on Chemical Mixtures) from NIH/NIEHS, Award Numbers R83622 (Statistical Models for Estimating the Health Impact of Air Quality Regulations) and RD83241701 (Estimation of the Risks to Human Health of PM and PM Components) from EPA, Award Number 4909-RFA11-1/12-3 (Causal Inference Methods for Estimating Long Term Health Effects of Air Quality Regulations) from HEI and Award Number K18 HS021991 (A Translational Framework for Methodological Rigor to Improve Patient Centered Outcomes in End of Life Cancer Research) from AHRQ. The content is solely the responsibility of the authors and does not necessarily represent the official views of the above Institutions. NR 35 TC 0 Z9 0 U1 2 U2 5 PU INT SOC BAYESIAN ANALYSIS PI PITTSBURGH PA CARNEGIE MELLON UNIV, DEPT STTISTICS, PITTSBURGH, PA 15213 USA SN 1931-6690 EI 1936-0975 J9 BAYESIAN ANAL JI Bayesian Anal. PD SEP PY 2015 VL 10 IS 3 BP 523 EP 552 DI 10.1214/14-BA922 PG 30 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA CO2PJ UT WOS:000358998700001 ER PT J AU Ziehr, DR Chen, MH Zhang, DJ Braccioforte, MH Moran, BJ Mahal, BA Hyatt, AS Basaria, SS Beard, CJ Beckman, JA Choueiri, TK D'Amico, AV Hoffman, KE Hu, JC Martin, NE Sweeney, CJ Trinh, QD Nguyen, PL AF Ziehr, David R. Chen, Ming-Hui Zhang, Danjie Braccioforte, Michelle H. Moran, Brian J. Mahal, Brandon A. Hyatt, Andrew S. Basaria, Shehzad S. Beard, Clair J. Beckman, Joshua A. Choueiri, Toni K. D'Amico, Anthony V. Hoffman, Karen E. Hu, Jim C. Martin, Neil E. Sweeney, Christopher J. Trinh, Quoc-Dien Nguyen, Paul L. TI Association of androgen-deprivation therapy with excess cardiac-specific mortality in men with prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate; prostatic neoplasms; antineoplastic agents; goserelin; leuprolide; coronary disease ID RADIATION-THERAPY; RANDOMIZED-TRIAL; SUPPRESSION; RADIOTHERAPY; BRACHYTHERAPY; SOCIETY; DISEASE; RISK AB Objectives To determine with excess cardiac-specific mortality (CSM) in men with prostate cancer and no cardiovascular comorbidity, coronary artery disease risk factors, or congestive heart failure (CHF) or past myocardial infarction (MI). Patients and Methods In all, 5077 men (median age 69.5 years) with cT1c-T3N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant ADT (median duration 4 months) between 1997 and 2006. Fine and Gray competing risks analysis evaluated the association of ADT with CSM, adjusting for age, year of brachytherapy, and ADT treatment propensity score among men in groups defined by cardiac comorbidity. Results After a median follow-up of 4.8 years, no association was detected between ADT and CSM in men with no cardiac risk factors (1.08% at 5 years for ADT vs 1.27% at 5 years for no ADT, adjusted hazard ratio (AHR) 0.83; 95% confidence interval (CI), 0.39-1.78; P = 0.64; n = 2653) or in men with diabetes mellitus, hypertension, or hypercholesterolaemia (2.09% vs 1.97%, AHR 1.33; 95% CI 0.70-2.53; P = 0.39; n = 2168). However, ADT was associated with significantly increased CSM in men with CHF or MI (AHR 3.28; 95% CI 1.01-10.64; P = 0.048; n = 256). In this subgroup, the 5-year cumulative incidence of CSM was 7.01% (95% CI 2.82-13.82%) for ADT vs 2.01% (95% CI 0.38-6.45%) for no ADT. Conclusion ADT was associated with a 5% absolute excess risk of CSM at 5 years in men with CHF or prior MI, suggesting that administering ADT to 20 men in this potentially vulnerable subgroup could result in one cardiac death. C1 [Ziehr, David R.; Mahal, Brandon A.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Ming-Hui; Zhang, Danjie] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Braccioforte, Michelle H.; Moran, Brian J.] Prostate Canc Fdn Chicago, Westmont, IL USA. [Hyatt, Andrew S.; Beard, Clair J.; D'Amico, Anthony V.; Martin, Neil E.; Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Dana Farber Canc Inst, Med Oncol, Boston, MA USA. Brigham & Womens Hosp, Boston, MA USA. [Basaria, Shehzad S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. [Beckman, Joshua A.] Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Trinh, Quoc-Dien] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Hu, Jim C.] Univ Calif Los Angeles, Med Ctr, Dept Urol, Los Angeles, CA USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 44 Binney St,75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu RI Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Beckman, Joshua/0000-0001-8332-8439 FU Fitz's Cancer Warriors; Prostate Cancer Foundation FX This work is supported by Fitz's Cancer Warriors, David and Cynthia Chapin, the Prostate Cancer Foundation, Hugh Simons in honour of Frank and Anne Simons, and a grant from an anonymous family foundation. NR 25 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD SEP PY 2015 VL 116 IS 3 BP 358 EP 365 DI 10.1111/bju.12905 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CO6HF UT WOS:000359257100012 PM 25124891 ER PT J AU Wadt, KAW Aoude, LG Johansson, P Solinas, A Pritchard, A Crainic, O Andersen, MT Kiilgaard, JF Heegaard, S Sunde, L Federspiel, B Madore, J Thompson, JF McCarthy, SW Goodwin, A Tsao, H Jonsson, G Busam, K Gupta, R Trent, JM Gerdes, AM Brown, KM Scolyer, RA Hayward, NK AF Wadt, K. A. W. Aoude, L. G. Johansson, P. Solinas, A. Pritchard, A. Crainic, O. Andersen, M. T. Kiilgaard, J. F. Heegaard, S. Sunde, L. Federspiel, B. Madore, J. Thompson, J. F. McCarthy, S. W. Goodwin, A. Tsao, H. Jonsson, G. Busam, K. Gupta, R. Trent, J. M. Gerdes, A. -M. Brown, K. M. Scolyer, R. A. Hayward, N. K. TI A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma SO CLINICAL GENETICS LA English DT Article DE BAP1; BCC; cancer predisposition syndrome; germline mutation; melanoma; unknown primary tumor ID UVEAL MELANOMA; MALIGNANT MESOTHELIOMA; CUTANEOUS MELANOMA; FAMILY; PHENOTYPE; CANCERS AB We report four previously undescribed families with germline BRCA1-associated protein-1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family. C1 [Wadt, K. A. W.; Andersen, M. T.; Gerdes, A. -M.] Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark. [Aoude, L. G.; Johansson, P.; Pritchard, A.; Hayward, N. K.] QIMR Berghofer Med Res Inst, Genet & Computat Biol, Brisbane, Qld, Australia. [Aoude, L. G.] Univ Queensland, Brisbane, Qld, Australia. [Solinas, A.; Crainic, O.; McCarthy, S. W.; Gupta, R.; Scolyer, R. A.] Royal Prince Alfred Hosp, Tissue Pathol & Diagnost Oncol, Sydney, NSW, Australia. [Kiilgaard, J. F.; Heegaard, S.] Univ Copenhagen, Glostrup Hosp, Dept Ophthalmol, Copenhagen, Denmark. [Heegaard, S.] Univ Copenhagen, Eye Pathol Inst, Dept Neurosci & Pharmacol, Copenhagen, Denmark. [Sunde, L.] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Federspiel, B.] Univ Copenhagen, Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark. [Madore, J.; Thompson, J. F.; McCarthy, S. W.; Scolyer, R. A.] Melanoma Inst Australia, North Sydney, Australia. [Thompson, J. F.; McCarthy, S. W.; Gupta, R.; Scolyer, R. A.] Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia. [Goodwin, A.] Royal Prince Alfred Hosp, Dept Canc Genet, Sydney, NSW, Australia. [Tsao, H.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Jonsson, G.] Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden. [Busam, K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Trent, J. M.] Translat Genom Res Inst, Phoenix, AZ USA. [Brown, K. M.] NCI, Lab Translat Genom, Bethesda, MD 20892 USA. RP Wadt, KAW (reprint author), Rigshosp, Dept Clin Genet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. EM Karin.wadt@rh.regionh.dk RI Pritchard, Antonia/F-4288-2010; Johansson, Peter/K-1053-2014; hayward, nicholas/C-1367-2015; OI Pritchard, Antonia/0000-0001-5336-0454; Johansson, Peter/0000-0001-7015-5452; hayward, nicholas/0000-0003-4760-1033; Sunde, Lone/0000-0002-8479-165X; Scolyer, Richard/0000-0002-8991-0013; Kiilgaard, Jens Folke/0000-0003-1054-1460 FU National Health and Medical Research Council of Australia (NHMRC); Cancer Council Queensland; Fight for sight, Denmark; Melanoma Research Alliance; Rigshospitalet; University Hospital of Copenhagen; US NIH [K24 CA14920]; Australia and Banking Group Limited; New Zealand Banking Group Limited; NHMRC FX Funding for this project was provided by the National Health and Medical Research Council of Australia (NHMRC), the Cancer Council Queensland, Fight for sight, Denmark, and the Melanoma Research Alliance. K. A. W. W. and L. G. A. receive PhD scholarships from Rigshospitalet, University Hospital of Copenhagen and the Australia and New Zealand Banking Group Limited Trustees respectively. Swedish Cancer Society, Swedish Research Council and Nordic Cancer Union. Aase og Ejnar Danielsens Fond. The Danish Medical Association Research Fund. H. T. is a recipient of a grant from US NIH K24 CA14920. N. K. H. is a recipient of a Senior Principal Research Fellowship from the NHMRC. The authors wish to thank the participants of the study for making this research possible. NR 22 TC 21 Z9 21 U1 1 U2 4 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 SEP PY 2015 VL 88 IS 3 BP 267 EP 272 DI 10.1111/cge.12501 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA CO3NL UT WOS:000359064800010 PM 25225168 ER PT J AU Lareau, CR Deren, ME Fantry, A Donahue, RMJ DiGiovanni, CW AF Lareau, Craig R. Deren, Matthew E. Fantry, Amanda Donahue, Rafe M. J. DiGiovanni, Christopher W. TI Does autogenous bone graft work? A logistic regression analysis of data from 159 papers in the foot and ankle literature SO FOOT AND ANKLE SURGERY LA English DT Review DE Autogenous bone graft; Foot; Ankle; Arthrodesis ID INTERNAL COMPRESSION ARTHRODESIS; SUBTALAR DISTRACTION ARTHRODESIS; RETROGRADE INTRAMEDULLARY NAIL; BLAIR TIBIOTALAR ARTHRODESIS; SEVERE PLANOVALGUS DEFORMITY; ACQUIRED FLATFOOT DEFORMITY; TIBIAL TENDON DYSFUNCTION; CROSS-SCREW FIXATION; TERM FOLLOW-UP; TRIPLE ARTHRODESIS AB Background: While autogenous cancellous iliac crest bone graft is the gold standard for foot and ankle surgery, it lacks Level I evidence. Although one third of all graft cases performed in the United States today rely on allograft, some surgeons believe no graft is necessary. We hypothesized that a systematic review of the foot and ankle literature would reveal that (1) autogenous bone graft during foot and ankle arthrodesis would demonstrate healing rates that were superior to the use of either using allograft or no bone graft at all, and (2) these differences would be even more dramatic in patients having risk factors that impair bone healing. To our knowledge, neither of these assessments to date has ever been performed with this body of literature. The goal of this study was to review the use and union rates of bone graft during foot and ankle arthrodesis and determine if autogenous bone graft was superior. Methods: A literature search was performed to include articles between 1959 and 2012 using autograft, allograft, and/or no bone graft for foot and/or ankle arthrodesis. Case reports involving fewer than four patients, investigations failing to incorporate outcome data, those involving orthobiologic augmentation, and those including vascularized graft, xenograft, or pediatric patients were excluded. Recorded search results included patient demographics, comorbidities, pre-operative diagnosis, surgical procedure, bone graft type and indication, union rate, method of fixation, patient satisfaction, all outcome scores, definition of healing/success, and any listed complications including revision. Final data were stratified based upon the type of graft material. Results: This search generated 953 related articles, of which 159 studies (5327 patients) met inclusion criteria. The majority (153/159) were retrospective case series. Systematic review demonstrated a trend toward higher union rates for cancellous autograft (OR 1.39, p = 0.11), structural autograft (OR 1.52, p = 0.09), and cancellous allograft (OR 1.31, p = 0.52) relative to no graft material, but none reached statistical significance. Compared to no graft, structural allograft trended toward worse performance (OR 0.62, p = 0.17). The overall probability of union was 93.7% for cancellous autograft, 94.2% for structural autograft, 93.3% for cancellous allograft, 91.4% for no graft, and 86.9% for structural allograft. When only comparing the 19 papers that included a no graft arm (91.9% union rate), data revealed the highest union using cancellous autograft (95.1%, OR 1.73, p = 0.09) and structural autograft (96.3%, OR 2.33, p = 0.06) while only 76% for structural allograft. No significant statistical association existed between union rates and other recorded variables. Conclusion: Systematic analysis of bone graft use in foot and ankle fusions favors the use of autograft and cancellous allograft for optimized healing rates, although no differences were statistically significant. If we assume that graft material been chosen for more complex procedures having lower anticipated union rates, then these data lend further support to the use of autograft and cancellous allograft. Level of Evidence: Level IV. (c) 2015 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved. C1 [Lareau, Craig R.] OrthoCarolina Foot & Ankle Inst, Dept Orthopaed, Charlotte, NC USA. [Deren, Matthew E.; Fantry, Amanda] Brown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA. [Deren, Matthew E.; Fantry, Amanda] Rhode Isl Hosp, Providence, RI 02903 USA. [Donahue, Rafe M. J.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37232 USA. [DiGiovanni, Christopher W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Fantry, A (reprint author), Brown Univ, Warren Alpert Med Sch, Dept Orthopaed, 593 Eddy St, Providence, RI 02903 USA. EM amanda.fantry@gmail.com FU BESPA; Biomimetic; Curamedix, Inc.; Extremity Medical, Inc.; Saunders/Mosby-Elsevier; Springer; Wolters Kluwer Health-Lippincott Williams Wilkins; Wright Medical Technology, Inc. FX Dr. DiGiovanni is a paid consultant to the following companies, although no financial or industry support was provided for this paper: BESPA: Paid consultant Biomimetic: Paid consultant; Paid presenter or speaker; Research support Curamedix, Inc.: Other financial or material support Extremity Medical, Inc.: Paid consultant; Paid presenter or speaker; Stock or stock Options Extremity Medical, Inc.: IP royalties Foot and Ankle International: Editorial or governing board Paragon 28: Stock or stock Options Performance Orthotics, Inc.: Other financial or material support Saunders/Mosby-Elsevier: Publishing royalties, financial or material support Springer: Publishing royalties, financial or material support Wolters Kluwer Health-Lippincott Williams & Wilkins: Publishing royalties, financial or material support Wright Medical Technology, Inc.: Paid consultant; Paid presenter or speaker; Research support; Stock or stock Options. NR 168 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1268-7731 EI 1460-9584 J9 FOOT ANKLE SURG JI Foot Ankle Surg. PD SEP PY 2015 VL 21 IS 3 BP 150 EP 159 DI 10.1016/j.fas.2015.03.008 PG 10 WC Orthopedics SC Orthopedics GA CN9XF UT WOS:000358803100003 PM 26235852 ER PT J AU Cychosz, CC Phisitkul, P Belatti, DA Glazebrook, MA DiGiovanni, CW AF Cychosz, Christopher C. Phisitkul, Phinit Belatti, Daniel A. Glazebrook, Mark A. DiGiovanni, Christopher W. TI Response to Letter to the Editor on "Gastrocnemius recession for foot and ankle conditions in adults: Evidence-based recommendations" SO FOOT AND ANKLE SURGERY LA English DT Letter ID RELIABILITY; MOTION; RANGE C1 [Cychosz, Christopher C.; Belatti, Daniel A.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Phisitkul, Phinit] Univ Iowa Hosp & Clin, Dept Orthopaed & Rehabil, Iowa City, IA 52242 USA. [Glazebrook, Mark A.] Dalhousie Univ, Orthopaed Surg, Halifax, NS, Canada. [DiGiovanni, Christopher W.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Phisitkul, P (reprint author), Univ Iowa Hosp & Clin, 0102X JPP,200 Hawkins Dr, Iowa City, IA 52242 USA. EM phinit-phisitkul@uiowa.edu NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1268-7731 EI 1460-9584 J9 FOOT ANKLE SURG JI Foot Ankle Surg. PD SEP PY 2015 VL 21 IS 3 BP 226 EP 226 DI 10.1016/j.fas.2015.06.001 PG 1 WC Orthopedics SC Orthopedics GA CN9XF UT WOS:000358803100022 PM 26235871 ER PT J AU Alosco, ML Hayes, SM AF Alosco, Michael L. Hayes, Scott M. TI Structural brain alterations in heart failure: a review of the literature and implications for risk of Alzheimer's disease SO HEART FAILURE REVIEWS LA English DT Review DE Heart failure; Alzheimer's disease; Cerebrovascular disease; MRI; DTI; Medial temporal lobe ID CEREBRAL-BLOOD-FLOW; MILD COGNITIVE IMPAIRMENT; MEDIAL TEMPORAL-LOBE; WHITE-MATTER HYPERINTENSITIES; AMYLOID-BETA; CARDIORESPIRATORY FITNESS; DEPRESSIVE SYMPTOMS; EARLY-DIAGNOSIS; OLDER-ADULTS; DEMENTIA AB Cardiovascular disease is a recognized contributor to the pathogenesis of Alzheimer's disease (AD). Heart failure (HF) is a cardiovascular subtype that can be used to model the contribution of cardiovascular disease to AD. Neuroimaging research indicates that HF patients exhibit a diverse range of structural brain alterations and epidemiological studies suggest HF may be an important risk factor for AD. The neural alterations observed in HF may overlap with those observed in AD and contribute to increased risk of AD in HF patients. To examine this possibility, we reviewed structural MRI studies in persons with HF. We examined subcortical brain regions affected in the early stages of AD (medial temporal lobes), as well as cortical alterations that typically occur in the later stages of AD. Our review indicates that patients with HF exhibit greater neural atrophy and white matter microstructural alterations of nearly every region of the Papez circuit (e.g., hippocampus, cingulate gyrus, thalamus, mammillary bodies, and fornix), as well-significant alterations in cortical and cerebellar regions. Based on animal research and past work in AD patients, the mechanisms for structural brain changes in HF may stem from reductions in cerebral blood flow subsequent to cardiac deficiency. This review supports the hypothesis that HF may contribute to AD risk via widespread structural brain changes, including many of the same regions affected by AD. Case-controlled prospective neuroimaging studies with long-term follow-ups are needed to clarify the risk of AD in HF and elucidate the neural underpinnings of AD risk in HF. C1 [Alosco, Michael L.; Hayes, Scott M.] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02114 USA. [Alosco, Michael L.; Hayes, Scott M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Alosco, Michael L.] Kent State Univ, Dept Psychol Sci, Kent, OH 44242 USA. [Hayes, Scott M.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. RP Alosco, ML (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02114 USA. EM aloscomichael@gmail.com FU Department of Veterans Affairs, Rehabilitation Research & Development Service [e7822w] FX This work was supported by the Department of Veterans Affairs, Rehabilitation Research & Development Service [Career Development Award e7822w awarded to SMH]. The contents of this article do not represent the views of the US Department of Veterans Affairs or the US Government. NR 87 TC 4 Z9 4 U1 0 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 EI 1573-7322 J9 HEART FAIL REV JI Heart Fail. Rev. PD SEP PY 2015 VL 20 IS 5 BP 561 EP 571 DI 10.1007/s10741-015-9488-5 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO4XC UT WOS:000359163200004 PM 25896528 ER PT J AU Ramirez-Avila, L Regan, S Chetty, S Giddy, J Ross, D Katz, JN Freedberg, KA Losina, E Walensky, RP Bassett, IV AF Ramirez-Avila, Lynn Regan, Susan Chetty, Senica Giddy, Janet Ross, Douglas Katz, Jeffrey N. Freedberg, Kenneth A. Losina, Elena Walensky, Rochelle P. Bassett, Ingrid V. TI HIV testing rates, prevalence, and knowledge among outpatients in Durban, South Africa: Time trends over four years SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE HIV; AIDS; epidemiology; HIV testing; HIV prevalence; HIV knowledge; time trends; South Africa ID CARE AB The HIV public health messages in South Africa have increased. Our objective was to evaluate changes over time in HIV testing behaviour, prevalence and knowledge. We prospectively enrolled adults (>= 18 years) prior to HIV testing at one urban and one peri-urban outpatient department in Durban, South Africa. A baseline questionnaire administered before testing included the number of prior HIV tests and four knowledge items. We used test results to estimate previously undiagnosed HIV prevalence among those tested. We assessed linear trends over enrollment. From November 2006 to August 2010, 5229 subjects enrolled and 4877 (93%) were HIV tested and had results available. Subjects reporting prior testing over time increased, from 13% in study year 1 to 42% in year 4 (linear trend p < 0.001). The HIV prevalence among those tested declined steadily and significantly over time, from 64% of enrollees in study year 1 to 39% in the final year (linear trend p < 0.001). The percentage of subjects who recognised that medicine can help people with HIV live longer increased from 80% in study year 1 to 96% in study year 4. Rates of HIV testing have increased and prevalence among those tested has decreased in outpatients in Durban, South Africa. C1 [Ramirez-Avila, Lynn] Univ Calif Los Angeles, Mattel Childrens Hosp, Div Pediat Infect Dis, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ramirez-Avila, Lynn] Boston Childrens Hosp, Div Infect Dis, Boston, MA USA. [Ramirez-Avila, Lynn; Regan, Susan; Freedberg, Kenneth A.; Losina, Elena; Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Regan, Susan; Freedberg, Kenneth A.; Losina, Elena; Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Chetty, Senica; Giddy, Janet] McCord Hosp, Durban, South Africa. [Ross, Douglas] St Marys Hosp, Durban, South Africa. [Katz, Jeffrey N.; Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Katz, Jeffrey N.; Freedberg, Kenneth A.; Losina, Elena] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Katz, Jeffrey N.; Freedberg, Kenneth A.; Losina, Elena] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Katz, Jeffrey N.; Losina, Elena] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Freedberg, Kenneth A.; Losina, Elena; Walensky, Rochelle P.; Bassett, Ingrid V.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Freedberg, Kenneth A.; Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Ramirez-Avila, L (reprint author), Univ Calif Los Angeles, Mattel Childrens Hosp, Div Pediat Infect Dis, 10833 Conte Ave,22-442 MDCC, Los Angeles, CA 90095 USA. EM lynnramirez@mednet.ucla.edu FU National Institute of Allergy and Infectious Disease [T32 AI 007433, K23 AI 068458, K24 AI062476, R01 AI058736]; Health and Human Services Health Disparities Post-Graduate Fellowship; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [T32 HD 055148-02]; Harvard University Center for AIDS Research [P30 AI060354]; National Institute of Mental Health [R01 MH090326, R01 MH073445]; Claflin Distinguished Scholar Award; Burke Global Health Fellowship; Harvard Catalyst [UL1 RR 025758] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported in part by the National Institute of Allergy and Infectious Disease: T32 AI 007433; K23 AI 068458; K24 AI062476; R01 AI058736; Health and Human Services Health Disparities Post-Graduate Fellowship; the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) T32 HD 055148-02, the Harvard University Center for AIDS Research P30 AI060354; the National Institute of Mental Health: R01 MH090326; R01 MH073445; the Claflin Distinguished Scholar Award, the Burke Global Health Fellowship and the Harvard Catalyst (UL1 RR 025758). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 17 TC 1 Z9 1 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0956-4624 EI 1758-1052 J9 INT J STD AIDS JI Int. J. STD AIDS PD SEP PY 2015 VL 26 IS 10 BP 704 EP 709 DI 10.1177/0956462414551234 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CN9XE UT WOS:000358803000003 PM 25228664 ER PT J AU Reinshagen, C Ruess, D Walcott, BP Molcanyi, M Goldbrunner, R Rieger, B AF Reinshagen, Clemens Ruess, Daniel Walcott, Brian P. Molcanyi, Marek Goldbrunner, Roland Rieger, Bernhard TI A novel minimally invasive technique for lumbar decompression, realignment, and navigated interbody fusion SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Degenerative spondylolisthesis; Interbody; Lumbar fusion; Minimally invasive ID SURGERY; SPONDYLOLISTHESIS; SPINE; REDUCTION; OUTCOMES AB We present a novel, minimally invasive, navigation-guided approach for surgical treatment of degenerative spondylolisthesis (DS) that is a hybrid of the two most common techniques, posterior interbody fusion (PLIF) and transforaminal interbody fusion (TLIF). DS is an acquired condition with intersegmental instability of one or more lumbar motion segments. Seven patients with single level lumbar DS underwent lumbar arthrodesis utilizing the hybrid technique (HLIF) in our center. Using a standard unilateral midline approach a decompression and partial facetectomy on one side was performed, allowing for implantation of a specially designed interbody cage. Pedicle screws were placed using neuronavigation in a vertical vector on the side of the partial facetectomy and dorsolaterally (percutaneous) on the contralateral side. Patient and operative data, numeric rating scale (NRS) pain scores, core outcome measures index (COMI) and Oswestry disability index (ODI) were recorded preoperatively as well as 6 weeks, 3 months, 6 months and 1 year after surgery. All patients completed the 1 year follow-up. There was significant postoperative improvement of NRS, COMI and ODI scores at all postoperative follow-up time points (p < 0.05). The radiological assessments of realignment showed a reduction of listhesis from an average of 21.04% (standard deviation [SD] 5.1) preoperatively to 9.14% (SD 4.0) postoperatively (p < 0.001). The average blood loss was 492 ml. Post-procedure CT scans demonstrated correct implant placement in all but one patient who required a revision of a single pedicle screw. HLIF allows thorough decompression as well as realignment and interbody fusion for patients with DS and may help reduce tissue trauma in comparison to other minimally invasive lumbar fusion techniques. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Reinshagen, Clemens; Ruess, Daniel; Molcanyi, Marek; Goldbrunner, Roland; Rieger, Bernhard] Univ Cologne, Dept Gen Neurosurg, D-50937 Cologne, Germany. [Reinshagen, Clemens] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA USA. [Reinshagen, Clemens] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Walcott, Brian P.] Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA USA. [Molcanyi, Marek] Univ Cologne, Fac Med, Inst Neurophysiol, D-50937 Cologne, Germany. [Rieger, Bernhard] Univ Dresden, Dept Neurosurg, Dresden, Germany. RP Rieger, B (reprint author), Univ Cologne, Dept Gen Neurosurg, Kerpener Str 62, D-50937 Cologne, Germany. EM bernhard.rieger.com@gmail.com OI Reinshagen, Clemens/0000-0002-8524-4578 NR 27 TC 3 Z9 4 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2015 VL 22 IS 9 BP 1484 EP 1490 DI 10.1016/j.jocn.2015.03.019 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CO4YU UT WOS:000359167600021 PM 26100155 ER PT J AU Forsyth, TM Bi, WL Abedalthagafi, M Dunn, IF Chiocca, EA AF Forsyth, Tiara M. Bi, Wenya Linda Abedalthagafi, Malak Dunn, Ian F. Chiocca, E. Antonio TI Extracranial growth of glioblastoma multiforme SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Extracranial glioblastoma; Glioma invasion; Glioma metastasis ID METASTASIS AB We present a 59-year-old woman who noted an enlarging lump on her forehead 6 months after a left frontotemporal craniotomy for tumor resection and chemoradiation of her primary glioblastoma multiforme (GBM). GBM is a highly aggressive intracranial neoplasm associated with the shortest survival time of any primary central nervous system malignancy. Extracranial metastasis is rare, especially without previous surgical disruption of the dura and calvarium, which has been postulated to cause seeding of the extracranial space with tumor cells. This patient's MRI revealed tumor recurrence for which she underwent repeat resection. Histopathology confirmed GBM with unmethylated O-6-methylguanine-DNA methyltransferase and wildtype isocitrate dehydrogenase 1 status, as well as tumor invasion through the bone and subdermal space. The genetic and molecular factors that predict extracranial invasion remain unclear and require further investigation. Emerging data on circulating tumor cells in GBM patients indicate that extraaxial metastasis may be part of the disease course in some, particularly in long term survivors. Furthermore, the proximity of calvarial and scalp lesions to previous surgical sites and the time course in which they emerge after surgery suggests that iatrogenic seeding may also play a role in metastasis. With heightened awareness of the phenomenon, surgical strategies such as watertight approximation of the dura, bone flap replacement, or changing surgical instruments once the intradural component is complete may prove useful to prevent seeding. Prophylactic craniospinal irradiation may also be an appropriate tool in patients at high risk for metastasis, although this population is difficult to identify. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Forsyth, Tiara M.; Bi, Wenya Linda; Dunn, Ian F.; Chiocca, E. Antonio] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Abedalthagafi, Malak] Brigham & Womens Hosp, Dept Neuropathol, Boston, MA 02115 USA. [Dunn, Ian F.; Chiocca, E. Antonio] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 15 Francis St, Boston, MA 02115 USA. EM eachiocca@partners.org NR 14 TC 1 Z9 1 U1 3 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2015 VL 22 IS 9 BP 1521 EP 1523 DI 10.1016/j.jocn.2015.03.018 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CO4YU UT WOS:000359167600033 PM 25956620 ER PT J AU Chan, JL Kucyi, A DeSouza, JFX AF Chan, Jason L. Kucyi, Aaron DeSouza, Joseph F. X. TI Stable Task Representations under Attentional Load Revealed with Multivariate Pattern Analysis of Human Brain Activity SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID EVENT-RELATED FMRI; POSTERIOR PARIETAL CORTEX; SUPPLEMENTARY EYE FIELD; WORKING-MEMORY TASKS; PREFRONTAL CORTEX; ANTISACCADE TASK; ANTI-SACCADES; PRO-SACCADES; PERFORMANCE; ACTIVATION AB Performing multiple tasks concurrently places a load on limited attentional resources and results in disrupted task performance. Although human neuroimaging studies have investigated the neural correlates of attentional load, how attentional load affects task processing is poorly understood. Here, task-related neural activity was investigated using fMRI with conventional univariate analysis and multivariate pattern analysis (MVPA) while participants performed blocks of prosaccades and antisaccades, either with or without a rapid serial visual presentation (RSVP) task. Performing prosaccades and antisaccades with RSVP increased error rates and RTs, decreased mean activation in frontoparietal brain areas associated with oculomotor control, and eliminated differences in activation between prosaccades and antisaccades. However, task identity could be decoded from spatial patterns of activation both in the absence and presence of an attentional load. Furthermore, in the FEFs and intraparietal sulcus, these spatial representations were found to be similar using cross-trial-type MVPA, which suggests stability under attentional load. These results demonstrate that attentional load may disrupt the strength of task-related neural activity, rather than the identity of task representations. C1 [Chan, Jason L.] Univ Western Ontario, London, ON N6A 5K8, Canada. [Kucyi, Aaron] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Kucyi, Aaron] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Kucyi, Aaron] Massachusetts Gen Hosp, Boston, MA 02114 USA. [DeSouza, Joseph F. X.] York Univ, Toronto, ON M3J 2R7, Canada. RP Chan, JL (reprint author), Univ Western Ontario, Robarts Res Inst, 100 Perth Dr, London, ON N6A 5K8, Canada. EM jchan529@uwo.ca OI DeSouza, Joseph /0000-0001-6931-0849 FU York University, Faculty of Health; Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant; NSERC USRA; Canadian Institutes of Health Research (CIHR) MD/PhD studentship; CIHR doctoral research award FX We thank B. Coe and S. David for technical support. This research was supported by funding from the York University, Faculty of Health, and the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant to J. F. X. D. J. L. C. was supported by an NSERC USRA and a Canadian Institutes of Health Research (CIHR) MD/PhD studentship. A. K. was supported by a CIHR doctoral research award. NR 55 TC 1 Z9 1 U1 0 U2 2 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 2015 VL 27 IS 9 BP 1789 EP 1800 DI 10.1162/jocn_a_00819 PG 12 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CN9KW UT WOS:000358768200009 PM 25941872 ER PT J AU Ramezani, A Dubrovsky, L Pushkarsky, T Sviridov, D Karandish, S Raj, DS Fitzgerald, ML Bukrinsky, M AF Ramezani, Ali Dubrovsky, Larisa Pushkarsky, Tatiana Sviridov, Dmitri Karandish, Sara Raj, Dominic S. Fitzgerald, Michael L. Bukrinsky, Michael TI Stimulation of Liver X Receptor Has Potent Anti-HIV Effects in a Humanized Mouse Model of HIV Infection SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CASSETTE TRANSPORTER A1; T-CELL DEPLETION; LIPID RAFTS; PREEXPOSURE PROPHYLAXIS; MEMBRANE MICRODOMAINS; CHOLESTEROL EFFLUX; IMMUNE-RESPONSES; DEFICIENT MICE; REPLICATION AB Previous studies demonstrated that liver X receptor (LXR) agonists inhibit human immunodeficiency virus (HIV) replication by upregulating cholesterol transporter ATP-binding cassette A1 (ABCA1), suppressing HIV production, and reducing infectivity of produced virions. In this study, we extended these observations by analyzing the effect of the LXR agonist T0901317 [N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide] on the ongoing HIV infection and investigating the possibility of using LXR agonist for pre-exposure prophylaxis of HIV infection in a humanized mouse model. Pre-exposure of monocyte-derived macrophages to T0901317 reduced susceptibility of these cells to HIV infection in vitro. This protective effect lasted for up to 4 days after treatment termination and correlated with upregulated expression of ABCA1, reduced abundance of lipid rafts, and reduced fusion of the cells with HIV. Pre-exposure of peripheral blood leukocytes to T0901317 provided only a short-term protection against HIV infection. Treatment of HIV-exposed humanized mice with LXR agonist starting 2 weeks postinfection substantially reduced viral load. When eight humanized mice were pretreated with LXR agonist prior to HIV infection, five animals were protected from infection, two had viral load at the limit of detection, and one had viral load significantly reduced relative to mock-treated controls. T0901317 pretreatment also reduced HIV-induced dyslipidemia in infected mice. In conclusion, these results reveal a novel link between LXR stimulation and cell resistance to HIV infection and suggest that LXR agonists may be good candidates for development as anti-HIV agents, in particular for pre-exposure prophylaxis of HIV infection. C1 [Ramezani, Ali; Dubrovsky, Larisa; Pushkarsky, Tatiana; Karandish, Sara; Raj, Dominic S.; Bukrinsky, Michael] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20037 USA. [Sviridov, Dmitri] Baker Int Diabet Inst, Heart & Diabet Inst, Melbourne, Vic, Australia. [Fitzgerald, Michael L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit,Ctr Computat & Integrat Biol, Boston, MA USA. RP Bukrinsky, M (reprint author), George Washington Univ, Sch Med & Hlth Sci, 2300 Eye St NW,Ross Hall 624, Washington, DC 20037 USA. EM mbukrins@gwu.edu FU National Institutes of Health National Heart, Lung, and Blood Institute [R01-HL112661, R01-HL093818]; National Institutes of Health National Institute of Allergy and Infectious Diseases [P30-AI087714]; National Health and Medical Research Council of Australia [GNT1019847, GNT586607] FX This work was supported by National Institutes of Health National Heart, Lung, and Blood Institute [Grants R01-HL112661 and R01-HL093818]; the National Institutes of Health National Institute of Allergy and Infectious Diseases [Grant P30-AI087714]; and National Health and Medical Research Council of Australia [Grants GNT1019847 and GNT586607]. NR 50 TC 2 Z9 2 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2015 VL 354 IS 3 BP 376 EP 383 DI 10.1124/jpet.115.224485 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CO2PU UT WOS:000358999900014 PM 26126533 ER PT J AU Eggener, SE Badani, K Barocas, DA Barrisford, GW Cheng, JS Chin, AI Corcoran, A Epstein, JI George, AK Gupta, GN Hayn, MH Kauffman, EC Lane, B Liss, MA Mirza, M Morgan, TM Moses, K Nepple, KG Preston, MA Rais-Bahrami, S Resnick, MJ Siddiqui, MM Silberstein, J Singer, EA Sonn, GA Sprenkle, P Stratton, KL Taylor, J Tomaszewski, J Tollefson, M Vickers, A White, WM Lowrance, WT AF Eggener, Scott E. Badani, Ketan Barocas, Daniel A. Barrisford, Glen W. Cheng, Jed-Sian Chin, Arnold I. Corcoran, Anthony Epstein, Jonathan I. George, Arvin K. Gupta, Gopal N. Hayn, Matthew H. Kauffman, Eric C. Lane, Brian Liss, Michael A. Mirza, Moben Morgan, Todd M. Moses, Kelvin Nepple, Kenneth G. Preston, Mark A. Rais-Bahrami, Soroush Resnick, Matthew J. Siddiqui, M. Minhaj Silberstein, Jonathan Singer, Eric A. Sonn, Geoffrey A. Sprenkle, Preston Stratton, Kelly L. Taylor, Jennifer Tomaszewski, Jeffrey Tollefson, Matt Vickers, Andrew White, Wesley M. Lowrance, William T. TI Gleason 6 Prostate Cancer: Translating Biology into Population Health SO JOURNAL OF UROLOGY LA English DT Review DE prostatic neoplasms; neoplasm grading; early detection of cancer; watchful waiting; prostatectomy ID 2005 INTERNATIONAL-SOCIETY; TRIAL RISK CALCULATOR; CONSENSUS CONFERENCE; NEEDLE BIOPSIES; FOLLOW-UP; ADENOCARCINOMA; CARCINOMA; ANTIGEN; DIAGNOSIS; SURVEILLANCE AB Purpose: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. Materials and Methods: Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. Results: The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. Conclusions: The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening. C1 [Eggener, Scott E.] Univ Chicago, Chicago, IL 60637 USA. [Badani, Ketan] Mt Sinai, New York, NY USA. [Barocas, Daniel A.; Moses, Kelvin; Resnick, Matthew J.] Vanderbilt Univ, Nashville, TN 37235 USA. [Barrisford, Glen W.; Cheng, Jed-Sian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Preston, Mark A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chin, Arnold I.] Univ Calif Los Angeles, Los Angeles, CA USA. [Corcoran, Anthony] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Epstein, Jonathan I.] Johns Hopkins Univ, Baltimore, MD USA. [George, Arvin K.] NIH, Bethesda, MD 20892 USA. [Gupta, Gopal N.] Loyola Univ, Maywood, IL 60153 USA. [Hayn, Matthew H.] Tufts Univ, Maine Med Ctr, Portland, ME USA. [Kauffman, Eric C.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Lane, Brian] Michigan State Univ, Spectrum Hlth, Grand Rapids, MI USA. [Liss, Michael A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Mirza, Moben] Univ Kansas, Kansas City, KS USA. [Morgan, Todd M.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nepple, Kenneth G.] Univ Iowa, Iowa City, IA USA. [Rais-Bahrami, Soroush] Univ Alabama Birmingham, Birmingham, AL USA. [Siddiqui, M. Minhaj] Univ Maryland, Baltimore, MD 21201 USA. [Silberstein, Jonathan] Tulane Univ, New Orleans, LA 70118 USA. [Singer, Eric A.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Sonn, Geoffrey A.] Stanford Univ, Stanford, CA 94305 USA. [Sprenkle, Preston] Yale Univ, New Haven, CT USA. [Stratton, Kelly L.] Univ Oklahoma, Oklahoma City, OK USA. Baylor Coll Med, Houston, TX 77030 USA. MD Anderson Canc Ctr Cooper, Camden, NJ USA. [Tollefson, Matt] Mayo Clin, Rochester, MN USA. [Vickers, Andrew] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [White, Wesley M.] Univ Tennessee, Knoxville, TN USA. [Lowrance, William T.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. RP Lowrance, WT (reprint author), Univ Utah, Huntsman Canc Inst, Div Urol, Dept Surg, 1950 Circle Hope,6405, Salt Lake City, UT 84112 USA. EM will.lowrance@hci.utah.edu OI Vickers, Andrew/0000-0003-1525-6503; Rais-Bahrami, Soroush/0000-0001-9466-9925 FU NCI NIH HHS [P50 CA092629] NR 50 TC 24 Z9 24 U1 0 U2 9 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 SEP PY 2015 VL 194 IS 3 BP 626 EP 634 DI 10.1016/j.juro.2015.01.126 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CO4UW UT WOS:000359157200007 PM 25849602 ER PT J AU Li, T Zhang, CF Ding, YL Zhai, W Liu, K Bu, F Tu, T Sun, LX Zhu, W Zhou, FF Qi, WK Hu, JB Chen, HB Sun, XC AF Li, Tao Zhang, Chunfu Ding, Yanling Zhai, Wei Liu, Kui Bu, Fan Tu, Tao Sun, Lingxian Zhu, Wei Zhou, Fangfang Qi, Wenkai Hu, Jiabo Chen, Huabiao Sun, Xiaochun TI Umbilical cord-derived mesenchymal stem cells promote proliferation and migration in MCF-7 and MDA-MB-231 breast cancer cells through activation of the ERK pathway SO ONCOLOGY REPORTS LA English DT Article DE umbilical cord mesenchymal stem cells; proliferation; migration; ERK; MCF-7; MDA-MB-231 ID TUMOR MICROENVIRONMENT; BONE-MARROW; IN-VITRO; GROWTH; METASTASIS; ANGIOGENESIS; CARCINOMAS; CATENIN; BLOOD; SNAIL AB Mesenchymal stem cells (MSCs) are known to migrate to tumor tissues and to play an important role in cancer progression. However, the effects of MSCs on tumor progression remain controversial. The purpose of the present study was to detect the effects of human umbilical cord-derived MSCs (hUC-MSCs) on the human breast cancer cell lines MDA-MB-231 and MCF-7 in vitro and the underlying mechanisms. MSCs were isolated and identified from umbilical cord tissues. MDA-MB-231 and MCF-7 cells were treated with conditioned medium (CM) from 10 and 20% umbilical cord MSCs (UC-MSCs), and the resulting changes in proliferation and migration were investigated. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazohum bromide (MTT) and plate clone formation assays were used to assess the effect on proliferation, and the effects of CM on MDA-MB-231 and MCF-7 migration were assessed through scratch wound and Transwell migration assays. The expression of cell proliferation- and metastasis-related genes and proteins and activation of the ERK signaling pathway were analyzed by RT-PCR and western blot assays. UC-MSCs are characteristically similar to bone marrow MSCs (BM-MSCs) and exhibit multipotential differentiation capability (i.e., osteoblasts and adipocytes). The MTT, plate clone formation, scratch wound and Transwell migration assay results revealed that 10 and 20% CM promoted the proliferation and migration to higher levels than those observed in the control group. Our findings showed that UC-MSC-CM inhibited E-cadherin expression, increased the expression of N-cadherin and proliferating cell nuclear antigen (PCNA) and enhanced the expression of ZEB1, a transcription factor involved in epithelial-to-mesenchymal transition (EMT), through activation of the ERK pathway. U0126, an inhibitor of ERK, reversed the effects of UC-MSC-CM on breast cancer cell proliferation and migration. We conclude that UC-MSCs promote the proliferation and migration of breast cancer cell lines via activation of the ERK pathway. C1 [Li, Tao; Ding, Yanling; Zhai, Wei; Liu, Kui; Bu, Fan; Tu, Tao; Sun, Lingxian; Zhu, Wei; Zhou, Fangfang; Qi, Wenkai; Hu, Jiabo; Chen, Huabiao; Sun, Xiaochun] Jiangsu Univ, Jiangsu Key Lab Clin Lab Med, Sch Med, Zhenjiang 212013, Jiangsu, Peoples R China. [Zhang, Chunfu] Second Peoples Hosp Kunshan, Kunshan 215300, Jiangsu, Peoples R China. [Chen, Huabiao] Massachusetts Gen Hosp, Vaccine & Immunotherapy Ctr, Boston, MA 02114 USA. [Chen, Huabiao] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sun, XC (reprint author), Jiangsu Univ, Jiangsu Key Lab Clin Lab Med, Sch Med, 301 Xuefu Rd, Zhenjiang 212013, Jiangsu, Peoples R China. EM huabiao.chen@mgh.harvard.edu; xiaochun@ujs.edu.cn FU Foundation of Jiangsu University for Seniors [11JDG0089]; Innovation Project of Cultivating Graduates of Jiangsu Province [CXLX13_689]; Science Foundation of Kunshan [KS1331] FX The present study was supported by the Foundation of Jiangsu University for Seniors (grant no. 11JDG0089) and the Innovation Project of Cultivating Graduates of Jiangsu Province (grant no. CXLX13_689) and the Science Foundation of Kunshan (grant no. KS1331). NR 41 TC 5 Z9 6 U1 3 U2 22 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1021-335X EI 1791-2431 J9 ONCOL REP JI Oncol. Rep. PD SEP PY 2015 VL 34 IS 3 BP 1469 EP 1477 DI 10.3892/or.2015.4109 PG 9 WC Oncology SC Oncology GA CO5AX UT WOS:000359173100044 PM 26151310 ER PT J AU Stylianopoulos, T Economides, EA Baish, JW Fukumura, D Jain, RK AF Stylianopoulos, Triantafyllos Economides, Eva-Athena Baish, James W. Fukumura, Dai Jain, Rakesh K. TI Towards Optimal Design of Cancer Nanomedicines: Multi-stage Nanoparticles for the Treatment of Solid Tumors SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Drug delivery; Tumor microenvironment; Mathematical modeling; Nano-carriers ID DRUG-DELIVERY; BLOOD-FLOW; MODEL; DOXORUBICIN; STRATEGIES; SIZE; MACROMOLECULES; PENETRATION; HEMATOCRIT; TRANSPORT AB Conventional drug delivery systems for solid tumors are composed of a nano-carrier that releases its therapeutic load. These two-stage nanoparticles utilize the enhanced permeability and retention (EPR) effect to enable preferential delivery to tumor tissue. However, the size-dependency of the EPR, the limited penetration of nanoparticles into the tumor as well as the rapid binding of the particles or the released cytotoxic agents to cancer cells and stromal components inhibit the uniform distribution of the drug and the efficacy of the treatment. Here, we employ mathematical modeling to study the effect of particle size, drug release rate and binding affinity on the distribution and efficacy of nanoparticles to derive optimal design rules. Furthermore, we introduce a new multi-stage delivery system. The system consists of a 20-nm primary nanoparticle, which releases 5-nm secondary particles, which in turn release the chemotherapeutic drug. We found that tuning the drug release kinetics and binding affinities leads to improved delivery of the drug. Our results also indicate that multi-stage nanoparticles are superior over two-stage nano-carriers provided they have a faster drug release rate and for high binding affinity drugs. Furthermore, our results suggest that smaller nanoparticles achieve better treatment outcome. C1 [Stylianopoulos, Triantafyllos; Economides, Eva-Athena] Univ Cyprus, Canc Biophys Lab, Dept Mech & Mfg Engn, CY-1678 Nicosia, Cyprus. [Baish, James W.] Bucknell Univ, Dept Biomed Engn, Lewisburg, PA 17837 USA. [Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Stylianopoulos, T (reprint author), Univ Cyprus, Canc Biophys Lab, Dept Mech & Mfg Engn, CY-1678 Nicosia, Cyprus. EM tstylian@ucy.ac.cy; jain@steele.mgh.harvard.edu OI Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU European Commission; Marie-Curie Reintegration Grant [FP7-PIRG08-GA-2010-276894]; National Cancer Institute [P01-CA080124, R01-CA126642, R01-CA115767, R01-CA096915, R01-CA085140, T32-CA073479]; DoD Breast Cancer Research Innovator award [W81XWH-10-1-0016] FX Simulations were performed at the high performance computer systems of the Cancer Biophysics laboratory at the University of Cyprus and of the Partners Healthcare System at Massachusetts General Hospital. This work was supported by the European Commission with a Marie-Curie Reintegration Grant (FP7-PIRG08-GA-2010-276894) to TS and the National Cancer Institute (P01-CA080124, R01-CA126642, R01-CA115767, R01-CA096915, R01-CA085140, T32-CA073479, Federal Share Income Grant), and a DoD Breast Cancer Research Innovator award (W81XWH-10-1-0016) to RKJ. NR 36 TC 7 Z9 7 U1 4 U2 44 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 EI 1573-9686 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD SEP PY 2015 VL 43 IS 9 BP 2291 EP 2300 DI 10.1007/s10439-015-1276-9 PG 10 WC Engineering, Biomedical SC Engineering GA CN7WW UT WOS:000358646600025 PM 25670323 ER PT J AU Calkins, AW McMorran, KE Siegle, GJ Otto, MW AF Calkins, Amanda W. McMorran, Katherine E. Siegle, Greg J. Otto, Michael W. TI The Effects of Computerized Cognitive Control Training on Community Adults with Depressed Mood SO BEHAVIOURAL AND COGNITIVE PSYCHOTHERAPY LA English DT Article DE Depression; adults; attentional training; computer-aided psychotherapy ID CEREBRAL-BLOOD-FLOW; MAJOR DEPRESSION; UNIPOLAR DEPRESSION; EMOTION REGULATION; PREFRONTAL CORTEX; ANXIETY DISORDER; FMRI; METAANALYSIS; INDIVIDUALS; VALIDATION AB Background: Depression is frequently characterized by patterns of inflexible, maladaptive, and ruminative thinking styles, which are thought to result from a combination of decreased attentional control, decreased executive functioning, and increased negative affect. Cognitive Control Training (CCT) uses computer-based behavioral exercises with the aim of strengthening cognitive and emotional functions. A previous study found that severely depressed participants who received CCT exhibited reduced negative affect and rumination as well as improved concentration. Aims: The present study aimed to extend this line of research by employing a more stringent control group and testing the efficacy of three sessions of CCT over a 2-week period in a community population with depressed mood. Method: Forty-eight participants with high Beck Depression Inventory (BDI-II) scores were randomized to CCT or a comparison condition (Peripheral Vision Training; PVT). Results: Significant large effect sizes favoring CCT over PVT were found on the BDI-II (d = 0.73, p < .05) indicating CCT was effective in reducing negative mood. Additionally, correlations showed significant relationships between CCT performance (indicating ability to focus attention on CCT) and state affect ratings. Conclusions: Our results suggest that CCT is effective in altering depressed mood, although it may be specific to select mood dimensions. C1 [Calkins, Amanda W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [McMorran, Katherine E.] Catholic Univ Amer, Washington, DC 20064 USA. [Siegle, Greg J.] Univ Pittsburgh, Pittsburgh Med Ctr, Pittsburgh, PA 15260 USA. [Otto, Michael W.] Boston Univ, Boston, MA 02215 USA. RP Calkins, AW (reprint author), Massachusetts Gen Hosp, One Bowdoin Sq, Boston, MA 02114 USA. EM acalkins@partners.org OI Baker, Amanda/0000-0002-0103-5411 NR 37 TC 8 Z9 8 U1 7 U2 23 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1352-4658 EI 1469-1833 J9 BEHAV COGN PSYCHOTH JI Behav. Cognit. Psychther. PD SEP PY 2015 VL 43 IS 5 BP 578 EP 589 DI 10.1017/S1352465814000046 PG 12 WC Psychology, Clinical SC Psychology GA CN8VS UT WOS:000358724200006 PM 24589123 ER PT J AU Lindemer, ER Salat, DH Smith, EE Nguyen, K Fischl, B Greve, DN AF Lindemer, Emily R. Salat, David H. Smith, Eric E. Nguyen, Khoa Fischl, Bruce Greve, Douglas N. CA Alzheimer's Dis Neuroimaging Inita TI White matter signal abnormality quality differentiates mild cognitive impairment that converts to Alzheimer's disease from nonconverters SO NEUROBIOLOGY OF AGING LA English DT Article DE White matter signal abnormality; Mild cognitive impairment; Alzheimer's disease; FreeSurfer; Alzheimer's Disease Neuroimaging initiative; Hippocampus ID HUMAN CEREBRAL-CORTEX; SMALL VESSEL DISEASE; MAGNETIC-RESONANCE IMAGES; HIPPOCAMPAL VOLUME; MULTIPLE-SCLEROSIS; VASCULAR DEMENTIA; CORTICAL SURFACE; BRAIN VOLUME; AGING BRAIN; HYPERINTENSITIES AB The objective of this study was to assess how longitudinal change in the quantity and quality of white matter signal abnormalities (WMSAs) contributes to the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). The Mahalanobis distance of WMSA from normal-appearing white matter using T1-, T2-, and proton density-weighted MRI was defined as a quality measure for WMSA. Cross-sectional analysis of WMSA volume in 104 cognitively healthy older adults, 116 individuals with MCI who converted to AD within 3 years (mild cognitive impairment converter [MCI-C]), 115 individuals with MCI that did not convert in that time (mild cognitive impairment nonconverter [MCI-NC]), and 124 individuals with AD from the Alzheimer's Disease Neuroimaging Initiative revealed that WMSA volume was substantially greater in AD relative to the other groups but did not differ between MCI-NC and MCI-C. Longitudinally, MCI-C exhibited faster WMSA quality progression but not volume compared with matched MCI-NC beginning 18 months before MCI-C conversion to AD. The strongest difference in rate of change was seen in the time period starting 6 months before MCI-C conversion to AD and ending 6 months after conversion (p < 0.001). The relatively strong effect in this time period relative to AD conversion in the MCI-C was similar to the relative rate of change in hippocampal volume, a traditional imaging marker of AD pathology. These data demonstrate changes in white matter tissue properties that occur within WMSA in individuals with MCI that will subsequently obtain a clinical diagnosis of AD within 18 months. Individuals with AD have substantially greater WMSA volume than all MCI suggesting that there is a progressive accumulation of WMSA with progressive disease severity, and that quality change predates changes in this total volume. Given the timing of the changes in WMSA tissue quality relative to the clinical diagnosis of AD, these findings suggest that WMSAs are a critical component for this conversion and are a critical component of this clinical syndrome. (C) 2015 Elsevier Inc. All rights reserved. C1 [Lindemer, Emily R.; Fischl, Bruce] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Lindemer, Emily R.; Salat, David H.; Nguyen, Khoa; Fischl, Bruce; Greve, Douglas N.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Lindemer, Emily R.; Salat, David H.; Nguyen, Khoa; Fischl, Bruce; Greve, Douglas N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Salat, David H.] VA Boston Healthcare Syst, Boston, MA USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Fischl, Bruce] MIT, CSAIL, Cambridge, MA 02139 USA. RP Lindemer, ER (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM lindemer@mit.edu RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; DOD ADNI [W81XWH-12-2-0012]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; ADNI clinical sites in Canada; Northern California Institute for Research and Education; Alzheimer's Disease Cooperative Study at the University of California, San Diego FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec; Bristol-Myers Squibb Company; Eisai; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer; Piramal Imaging; Servier; Synarc; and Takeda Pharmaceutical Company. The Canadian Institutes of Rev December 5, 2013 Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. NR 79 TC 1 Z9 1 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2015 VL 36 IS 9 BP 2447 EP 2457 DI 10.1016/j.neurobiolaging.2015.05.011 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA CN9XI UT WOS:000358803400001 PM 26095760 ER PT J AU Chen, LJ Na, R Boldt, E Ran, QT AF Chen, Liuji Na, Ren Boldt, Erin Ran, Qitao TI NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure SO NEUROBIOLOGY OF AGING LA English DT Article DE Toxin exposure; Alzheimer's disease; Inflammation; NLRP3 inflammasome; Paraquat; Mitochondria; Oxidative stress; A beta ID ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; MICROGLIAL CELLS; NITRIC-OXIDE; MOUSE-BRAIN; TNF-ALPHA; IN-VIVO; BETA; NEUROTOXICITY; EXPRESSION AB Exposure to environmental toxins such as pesticides is implicated in increasing Alzheimer's disease risk. In this study, we investigated the long-term effects of paraquat exposure on cognition of Alzheimer's disease animal model APP/PS1 mice and wild-type (WT) mice. Our results showed that APP/PS1 mice had exacerbated cognition impairment and elevated A beta levels at 5 months after paraquat exposure, and that WT mice had cognition impairment at 5 and 16 months after paraquat exposure. In addition, increased mitochondrial oxidative stress and augmented brain inflammation were observed in both paraquat-exposed APP/PS1 mice and WT mice. Interestingly, activation of NLRP3 inflammasome, which triggers inflammation in response to mitochondrial stress, was enhanced in paraquat-exposed mice. Moreover, transgenic mice overexpressing Prdx3, a key enzyme in detoxifying mitochondrial H2O2, had suppressed NLRP3 inflammasome activation, reduced brain inflammation, and attenuated cognition impairment after paraquat exposure. Together, our results indicate that NLRP3 inflammasome activation induced by mitochondrial reactive oxygen species plays a key role in mediating paraquat-induced long-term cognition decline by elevating brain inflammation. Published by Elsevier Inc. C1 [Chen, Liuji; Na, Ren; Boldt, Erin; Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Ran, Qitao] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. RP Ran, QT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ran@uthscsa.edu FU Department of Veteran Affairs [5I10BX001382] FX The study was supported by a Merit Award (5I10BX001382 to Ran Q.) from the Department of Veteran Affairs. All procedures for handling the mice in this study were reviewed and approved by the Institutional Animal Care and Use Committees of the University of Texas Health Science Center at San Antonio and the South Texas Veterans Health Care System. NR 44 TC 7 Z9 7 U1 5 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2015 VL 36 IS 9 BP 2533 EP 2543 DI 10.1016/j.neurobiolaging.2015.05.018 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA CN9XI UT WOS:000358803400009 PM 26119225 ER PT J AU King, MR Firth, PG Yaster, M Ahmed, Z Mai, CL AF King, Michael R. Firth, Paul G. Yaster, Myron Ahmed, Zulfiqar Mai, Christine L. TI Malignant hyperthermia in the early days of pediatric anesthesia: an interview with anesthesiology pioneer, Dr. John F. Ryan SO PEDIATRIC ANESTHESIA LA English DT Article DE John Ryan; pediatric anesthesia; malignant hyperthermia; malignant hyperpyrexia; porcine stress syndrome; dantrolene ID SARCOPLASMIC-RETICULUM; SUSCEPTIBLE SWINE; SKELETAL-MUSCLE; DANTROLENE; DEATHS; FAMILY AB Dr. John F. Ryan (1935 - ), Associate Professor of Anaesthesia at the Harvard Medical School, influenced the careers of hundreds of residents and fellows-in-training while instilling in them his core values of resilience, hard work, and integrity. His authoritative textbook, A Practice of Anesthesia for Infants and Children, remains as influential today as it did when first published decades ago. Although he had had many accomplishments, he identified his experiences caring for patients with malignant hyperthermia and characterizing the early discovery of this condition as his defining contribution to medicine. Based on a series of interviews with Dr. Ryan, this article reviews a remarkable career that coincides with the dawn of modern pediatric anesthetic practice. C1 [King, Michael R.; Firth, Paul G.; Mai, Christine L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Firth, Paul G.; Mai, Christine L.] Massachusetts Eye & Ear Infirm, Dept Anesthesia, Boston, MA 02114 USA. [Yaster, Myron] Johns Hopkins Univ, Dept Anesthesiol, Baltimore, MD USA. [Yaster, Myron] Johns Hopkins Univ, Dept Crit Care Med, Baltimore, MD USA. [Yaster, Myron] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. [Ahmed, Zulfiqar] Wayne State Univ, Sch Med, Detroit, MI USA. [Ahmed, Zulfiqar] Anesthesia Associates Ann Arbor, Ann Arbor, MI USA. RP Mai, CL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care Med & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM cmai1@partners.org NR 27 TC 0 Z9 0 U1 1 U2 6 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 SEP PY 2015 VL 25 IS 9 BP 871 EP 876 DI 10.1111/pan.12697 PG 6 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA CN8NN UT WOS:000358698000002 PM 26036863 ER PT J AU Lucas, JT Ladra, MM MacDonald, SM Busse, PM Friedmann, AM Ebb, DH Marcus, KJ Tarbell, NJ Yock, TI AF Lucas, John T., Jr. Ladra, Matthew M. MacDonald, Shannon M. Busse, Paul M. Friedmann, Alison M. Ebb, David H. Marcus, Karen J. Tarbell, Nancy J. Yock, Torunn I. TI Proton therapy for pediatric and adolescent esthesioneuroblastoma SO PEDIATRIC BLOOD & CANCER LA English DT Article DE esthesioneuroblastoma; olfactory neuroblastoma; proton radiotherapy ID QUALITY-OF-LIFE; RADIATION-THERAPY; 2ND CANCERS; SALVAGE TREATMENT; PARANASAL SINUS; NASAL CAVITY; BRAIN-TUMORS; RADIOTHERAPY; PHOTON; CHILDREN AB BackgroundEsthesioneuroblastoma (EN) of the paranasal sinus comprises less than 3% of tumors of in pediatric and adolescent patients [1]. The collective adult literature indicates a critical role for radiotherapy in attaining cure [2], yet pediatric outcome data is limited. Radiation in pediatric patients with EN can cause significant morbidity due to the proximity of critical structures. Proton radiotherapy offers a potential dosimetric benefit that may improve long-term survival and toxicity outcomes in the pediatric population [3]. MethodsWe retrospectively identified eight patients treated for EN with proton radiotherapy from 2000-2013. Times to event clinical endpoints are summarized using the Kaplan-Meier methods and are from the date of radiotherapy completion. Toxicities are reviewed and graded according to CTCAE v. 4.0. ResultsMedian follow up was 4.6 years for survivors (range 0.8-9.4 years). The 4 year overall survival was 87.5%. Four of eight patients (one elective) had comprehensive neck radiotherapy. No local or regional failures were observed. Two patients failed distantly with diffuse leptomeningeal disease and intraparenchymal brain metastases, at 0.6 and 1.3 months respectively. Four patients developed radiation related late toxicities including endocrine dysfunction, two cases of grade 2 retinopathy and one case of grade 3 optic neuropathy. ConclusionsIn a limited cohort, proton radiotherapy appears to provide excellent locoregional disease control even in those patients with locally advanced disease and intracranial extension. Distant failure determined overall survival in our cohort. Toxicities were acceptable given disease location and extent. Pediatr Blood Cancer 2015;62:1523-1528. (c) 2015 Wiley Periodicals, Inc. C1 [Lucas, John T., Jr.] Wake Forest Sch Med, Dept Radiat Oncol, Winston Salem, NC USA. [Ladra, Matthew M.] Provis Ctr Proton Therapy, Knoxville, TN USA. [MacDonald, Shannon M.; Busse, Paul M.; Tarbell, Nancy J.; Yock, Torunn I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Friedmann, Alison M.; Ebb, David H.] Massachusetts Gen Hosp, Pediat, Boston, MA 02114 USA. [Marcus, Karen J.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Yock, TI (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Proton Ctr, 55 Fruit St,Room 110, Boston, MA 02114 USA. EM tyock@partners.org RI Lucas Jr., John/K-5243-2013 OI Lucas Jr., John/0000-0002-4139-4160 NR 41 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2015 VL 62 IS 9 BP 1523 EP 1528 DI 10.1002/pbc.25494 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CN8NL UT WOS:000358697800007 PM 25820437 ER PT J AU Rodin, D Balboni, M Mitchell, C Smith, PT VanderWeele, TJ Balboni, TA AF Rodin, Danielle Balboni, Michael Mitchell, Christine Smith, Patrick T. VanderWeele, Tyler J. Balboni, Tracy A. TI Whose role? Oncology practitioners' perceptions of their role in providing spiritual care to advanced cancer patients SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Palliative care; Religion; Spirituality; Spiritual care; Cancer ID QUALITY-OF-LIFE; PALLIATIVE CARE; MEDICAL-CARE; PHYSICIANS; END; ASSOCIATIONS; NURSES AB The purpose of this study is to determine how oncology nurses and physicians view their role in providing spiritual care (SC), factors influencing this perception, and how this belief affects SC provision. This is a survey-based, multisite study conducted from October 2008 to January 2009. All oncology physicians and nurses caring for advanced cancer patients at four Boston, MA cancer centers were invited to participate; 339 participated (response rate = 63 %). Nurses were more likely than physicians to report that it is the role of medical practitioners to provide SC, including for doctors (69 vs. 49 %, p < 0.001), nurses (73 vs. 49 %, p < 0.001), and social workers (81 vs. 63 %, p = 0.001). Among nurses, older age was the only variable that was predictive of this belief [adjusted odds ratio (AOR) 1.08; 1.01-1.16, p = 0.02]. For nurses, role perception was not related to actual SC provision to patients. In contrast, physicians' role perceptions were influenced by their intrinsic religiosity (AOR, 1.44; 95 % CI, 1.09-1.89; p = 0.01) and spirituality (AOR, 6.41; 95 % CI, 2.31-17.73, p < 0.001). Furthermore, physicians who perceive themselves as having a role in SC provision reported greater SC provision to their last advanced cancer patients seen in clinic, 69 % compared to 31 %, p < 0.001. Nurses are more likely than physicians to perceive medical practitioners as having a role in SC provision. Physicians' perceptions of their role in SC provision are influenced by their religious/spiritual characteristics and are predictive of actual SC provision to patients. Spiritual care training that includes improved understanding of clinicians' appropriate role in SC provision to severely ill patients may lead to increased SC provision. C1 [Rodin, Danielle] Univ Toronto, Dept Radiat Oncol, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada. [Rodin, Danielle; Mitchell, Christine; VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Balboni, Michael; Mitchell, Christine; Balboni, Tracy A.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Smith, Patrick T.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Balboni, Tracy A.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. RP Rodin, D (reprint author), Univ Toronto, Dept Radiat Oncol, Princess Margaret Canc Ctr, 610 Univ Ave,5th Floor, Toronto, ON M5G 2M9, Canada. EM danielle.rodin@rmp.uhn.on.ca FU American Society of Clinical Oncology; John Templeton Foundation; Healthcare Chaplaincy Award; University of Chicago Program in Religion and Medicine Faculty Scholars Award FX The authors received the following financial support for the research, authorship, and/or publication of this article: American Society of Clinical Oncology Young Investigator Award and Career Development Award (TAB), John Templeton Foundation Award (TJV), Healthcare Chaplaincy Award (TAB, TJV, and MJB), and University of Chicago Program in Religion and Medicine Faculty Scholars Award (MJB). NR 27 TC 5 Z9 5 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD SEP PY 2015 VL 23 IS 9 BP 2543 EP 2550 DI 10.1007/s00520-015-2611-2 PG 8 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA CN8GJ UT WOS:000358677600006 PM 25627924 ER PT J AU Baz, R Lin, HM Hui, AM Harvey, RD Colson, K Gallop, K Swinburn, P Laubach, J Berg, D Richardson, P AF Baz, R. Lin, H. M. Hui, A. -M. Harvey, R. D. Colson, K. Gallop, K. Swinburn, P. Laubach, J. Berg, D. Richardson, P. TI Development of a conceptual model to illustrate the impact of multiple myeloma and its treatment on health-related quality of life SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Multiple myeloma; Health-related quality of life; Conceptual model ID EXPERIENCES; WELL; EXPLORATION; THERAPIES; DISEASE; ISSUES AB Little qualitative research exploring the impact of multiple myeloma (MM) and its treatment on the health-related quality of life (HRQL) of patients has been published. This study aimed to explore the burden of MM symptoms and treatment and the impact of these on HRQL. A model was developed to illustrate key concepts and their interrelationships. Patients with MM were recruited to this cross-sectional, qualitative study through a patient panel and at two clinical sites in the USA. An interview discussion guide was developed using a review of published literature and interviews with experienced MM clinicians. In-depth, semistructured telephone interviews with MM patients were conducted to explore their experiences of the disease and its treatment. Data were analyzed using a thematic analysis approach. Twenty MM patients at various stages of treatment participated in open-ended, semistructured interviews. Patients reported both current and previous MM symptoms; most had experienced fatigue and pain. Other commonly reported symptoms were fractures, anemia, neuropathy, aches, and infections. MM treatment was found to have a negative impact on patients' HRQL; treatment-related adverse events included fatigue, neuropathy, insomnia, and gastrointestinal symptoms. MM treatment placed a substantial psychological and physical burden on patients, disrupting social activities, decreasing independence, and impacting on relationships. A model was developed to illustrate the relationship between these concepts. The conceptual model developed in this study illustrates the many aspects of MM and its treatment and how they can have a negative impact on patients' HRQL. C1 [Baz, R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA. [Lin, H. M.; Hui, A. -M.; Berg, D.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Harvey, R. D.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Colson, K.; Laubach, J.; Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gallop, K.] Oxford Outcomes, Oxford, England. [Swinburn, P.] MAPI Consultancy, London, England. RP Baz, R (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM rachid.baz@moffitt.org FU Millennium Pharmaceuticals, Inc. FX The authors would like to acknowledge the editorial assistance of Jane Saunders and Helen Johns of FireKite, part of the KnowledgePoint360 Group, an Ashfield Company, during the development of this publication, which was funded by Millennium Pharmaceuticals, Inc. The authors would also like to thank Katie Breheny, Kendra Debusk, and Rene Dickerhoof from Icon Plc for their assistance with data collection and analysis. NR 26 TC 2 Z9 2 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD SEP PY 2015 VL 23 IS 9 BP 2789 EP 2797 DI 10.1007/s00520-015-2644-6 PG 9 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA CN8GJ UT WOS:000358677600035 PM 25708126 ER PT J AU Cho, I Slight, SP Nanji, KC Seger, DL Maniam, N Fiskio, JM Dykes, PC Bates, DW AF Cho, Insook Slight, Sarah P. Nanji, Karen C. Seger, Diane L. Maniam, Nivethietha Fiskio, Julie M. Dykes, Patricia C. Bates, David W. TI The effect of provider characteristics on the responses to medication-related decision support alerts SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE Decision support; Medication safety; Prescribing; Provider characteristics; Quality ID PHYSICIAN ORDER ENTRY; DRUG SAFETY ALERTS; PRIMARY-CARE; AMBULATORY-CARE; PATIENT; SYSTEMS; PERFORMANCE; PERCEPTIONS; REMINDERS; WORKLOAD AB Background: Improving the quality of prescribing and appropriate handling of alerts remains a challenge for design and implementation of clinical decision support (CDS) and comparatively little is known about the effects that provider characteristics have on how providers respond to medication alerts. OBjectives: To investigate the relationship between provider characteristics and their response to medication alerts in the outpatient setting. Design and participants: Retrospective observational study using a prescription log from the automated electronic outpatient system for each of 478 providers using the system at primary care practices affiliated with 2 teaching hospitals, from 2009 to 2011 for six types of alerts. Provider characteristics were obtained from the hospital credentialing system and the Massachusetts Board of Registration in Medicine. Main measures: Override rates per 100 prescriptions and 100 alerts. Results: The providers' mean override rates per 100 prescriptions and per 100 alerts were 0.52 (95% confidence interval (CI), 0.46-0.58) and 0.42 (95% CI, 0.38-0.44) respectively. The physicians (n=422) on average overrode drug alerts with rates of 0.48 per 100 drugs and 0.44 per 100 warnings. Univariate analysis revealed that six physician characteristics (physician type, age, number of encounters, medical school ranking, residency hospital ranking, and acceptance of Medicaid) were significantly related to the override rate. Multiple regression showed that house staff were more likely to override than staff physicians (p<0.001), physicians with fewer than 13 average daily encounters were more likely to override than others with more than 13 encounters (p (range), <0.001-0.05), and graduates of the top 5 medical schools were more likely to override than the others (p=0.04). All six predictors together explained 30% and 50% of the variance in override rates, respectively. Conclusions: Consideration of six specific physician characteristics may help inform interventions to improve prescriber decision-making. Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Cho, Insook; Slight, Sarah P.; Dykes, Patricia C.; Bates, David W.] Brigham & Womens Hosp, Ctr Patient Safety Res & Practice, Div Gen Internal Med, Boston, MA 02120 USA. [Cho, Insook] Inha Univ, Dept Nursing, Inchon, South Korea. [Cho, Insook; Slight, Sarah P.; Nanji, Karen C.; Dykes, Patricia C.; Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. [Seger, Diane L.; Maniam, Nivethietha; Fiskio, Julie M.; Bates, David W.] Partners Healthcare Syst Inc, Wellesley, MA USA. [Slight, Sarah P.] Univ Durham, Sch Pharm Med & Hlth, Div Pharm, Stockton On Tees, England. [Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Cho, I (reprint author), Brigham & Womens Hosp, Ctr Patient Safety Res & Practice, Div Gen Internal Med, Boston, MA 02120 USA. EM Insook.cho@inha.ac.kr FU Centers for Education and Research on Therapeutics (CERT Grant) [U19HS021094]; Agency for Healthcare Research and Quality, Rockville, MD, USA; Korea Research Foundation Grant; Korean Government (MOEHRD) [KRF-2013R1A1A2006387] FX This research sponsored by the Centers for Education and Research on Therapeutics (CERT Grant # U19HS021094), Agency for Healthcare Research and Quality, Rockville, MD, USA. I.C. was supported by a Korea Research Foundation Grant, which was funded by the Korean Government (MOEHRD; No. KRF-2013R1A1A2006387). NR 30 TC 4 Z9 4 U1 4 U2 11 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 SEP PY 2015 VL 84 IS 9 BP 630 EP 639 DI 10.1016/j.ijmedinf.2015.04.006 PG 10 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA CN0DG UT WOS:000358082400003 PM 26004341 ER PT J AU Ito, M Kanno, S Nosho, K Sukawa, Y Mitsuhashi, K Kurihara, H Igarashi, H Takahashi, T Tachibana, M Takahashi, H Yoshii, S Takenouchi, T Hasegawa, T Okita, K Hirata, K Maruyama, R Suzuki, H Imai, K Yamamoto, H Shinomura, Y AF Ito, Miki Kanno, Shinichi Nosho, Katsuhiko Sukawa, Yasutaka Mitsuhashi, Kei Kurihara, Hiroyoshi Igarashi, Hisayoshi Takahashi, Taiga Tachibana, Mami Takahashi, Hiroaki Yoshii, Shinji Takenouchi, Toshinao Hasegawa, Tadashi Okita, Kenji Hirata, Koichi Maruyama, Reo Suzuki, Hiromu Imai, Kohzoh Yamamoto, Hiroyuki Shinomura, Yasuhisa TI Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colon polyp; BRAF; KRAS; Fusobacterium; microbiome; colorectum; miR-31; dysplasia; MLH1; serrated neoplasia pathway ID ISLAND METHYLATOR PHENOTYPE; REAL-TIME PCR; BRAF MUTATION; COLON-CANCER; 2 SIDES; EXPRESSION; DISEASE; LESIONS; MICROBIOTA; NEOPLASIA AB Human gut microbiota is being increasingly recognized as a player in colorectal cancers (CRCs). Evidence suggests that Fusobacterium nucleatum (F. nucleatum) may contribute to disease progression and is associated with CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in CRCs; however, to date, there are no reports about the relationship between F. nucleatum and molecular features in the early stage of colorectal tumorigenesis. Therefore, we investigated the presence of F. nucleatum in premalignant colorectal lesions. In total, 465 premalignant lesions (343 serrated lesions and 122 non-serrated adenomas) and 511 CRCs were studied. We determined the presence of F. nucleatum and analyzed its association with molecular features including CIMP, MSI and microRNA-31 status. F. nucleatum was detected in 24% of hyperplastic polyps, 35% of sessile serrated adenomas (SSAs), 30% of traditional serrated adenomas (TSAs) and 33% of non-serrated adenomas. F. nucleatum was more frequently detected in CIMP-high premalignant lesions than in CIMP-low/zero lesions (p=0.0023). In SSAs, F. nucleatum positivity increased gradually from sigmoid colon to cecum (p=0.042). F. nucleatum positivity was significantly higher in CRCs (56%) than in premalignant lesions of any histological type (p<0.0001). In conclusion, F. nucleatum was identified in premalignant colorectal lesions regardless of histopathology but was more frequently associated with CIMP-high lesions. Moreover, F. nucleatum positivity increased according to histological grade, suggesting that it may contribute to the progression of colorectal neoplasia. Our data also indicate that F. nucleatum positivity in SSAs may support the colorectal continuum concept. What's new? Changes in the microbial community in the human gut may contribute to colorectal cancer (CRC). Of particular interest are changes in populations of Fusobacterium nucleatum, which previous work has shown to be abundant in CRC tissues. In this study, F. nucleatum was detected in CRCs, as well as in premalignant lesions with elevated CpG island methylator phenotype status. In sessile serrated adenomas, F. nucleatum increased steadily from the sigmoid colon to the cecum, supporting the existence of a colorectal continuum. F. nucleatum may become increasingly abundant with histological grade and may influence CRC progression. C1 [Ito, Miki; Kanno, Shinichi; Nosho, Katsuhiko; Mitsuhashi, Kei; Kurihara, Hiroyoshi; Igarashi, Hisayoshi; Takahashi, Taiga; Tachibana, Mami; Shinomura, Yasuhisa] Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido 0608543, Japan. [Sukawa, Yasutaka] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sukawa, Yasutaka] Harvard Univ, Sch Med, Boston, MA USA. [Takahashi, Hiroaki] Keiyukai Sapporo Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan. [Yoshii, Shinji] NTT East Sapporo Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan. [Takenouchi, Toshinao] Keiyukai Sapporo Hosp, Dept Pathol, Sapporo, Hokkaido, Japan. [Hasegawa, Tadashi] Sapporo Med Univ, Sch Med, Dept Surg Pathol, Sapporo, Hokkaido 0608543, Japan. [Okita, Kenji; Hirata, Koichi] Sapporo Med Univ, Sch Med, Dept Surg Surg Oncol & Sci, Sapporo, Hokkaido 0608543, Japan. [Maruyama, Reo; Suzuki, Hiromu] Sapporo Med Univ, Sch Med, Dept Mol Biol, Sapporo, Hokkaido 0608543, Japan. [Imai, Kohzoh] Univ Tokyo, Inst Med Sci, Tokyo, Japan. [Yamamoto, Hiroyuki] St Marianna Univ, Sch Med, Div Gastroenterol & Hepatol, Kawasaki, Kanagawa, Japan. RP Nosho, K (reprint author), Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Chou Ku, S-1,W-16, Sapporo, Hokkaido 0608543, Japan. EM nosho@sapmed.ac.jp FU Japan Society for the Promotion of Science (JSPS) Challenging Exploratory Research [25670371]; Ono Cancer Research Foundation; Takeda Science Foundation; Suhara Memorial Foundation; Yuasa Memorial Foundation; Daiwa Securities Health Foundation FX Grant sponsor: Japan Society for the Promotion of Science (JSPS) Challenging Exploratory Research; Grant number: 25670371; Grant sponsors: Ono Cancer Research Foundation; Takeda Science Foundation; The Suhara Memorial Foundation; Yuasa Memorial Foundation; Daiwa Securities Health Foundation NR 51 TC 17 Z9 17 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD SEP PY 2015 VL 137 IS 6 BP 1258 EP 1268 DI 10.1002/ijc.29488 PG 11 WC Oncology SC Oncology GA CM6OT UT WOS:000357808900007 PM 25703934 ER PT J AU Butt, AA Yan, P Shaikh, OS Freiberg, MS Lo Re, V Justice, AC Sherman, KE AF Butt, A. A. Yan, P. Shaikh, O. S. Freiberg, M. S. Lo Re, V., III Justice, A. C. Sherman, K. E. CA ERCHIVES Elect Retrieved Cohort TI Virologic response and haematologic toxicity of boceprevir- and telaprevir-containing regimens in actual clinical settings SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE boceprevir; directly acting antiviral agents; ERCHIVES; haematologic toxicity; sustained virologic response; telaprevir ID HEPATITIS-C VIRUS; TREATMENT-NAIVE PATIENTS; PHASE-2 TRIAL; INFECTION; RIBAVIRIN; SURVIVAL; PEGINTERFERON; SIMEPREVIR; SOFOSBUVIR; ALPHA-2A AB Effectiveness, safety and tolerability of boceprevir (BOC) and telaprevir (TPV) in actual clinical settings remain unknown. We determined rates of sustained virologic response (SVR) and haematologic adverse effects among persons treated with BOC- or TPV-containing regimens, compared with pegylated interferon/ribavirin (PEG/RBV). Using an established cohort of hepatitis C virus (HCV)-infected persons, Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), we identified those treated with a BOC- or TPV-containing regimen and HCV genotype 1-infected controls treated with PEG/RBV. We excluded those with HIV co-infection and missing HCV RNA values to determine SVR. Primary endpoints were SVR (undetectable HCV RNA >= 12 weeks after treatment completion) and haematologic toxicity (grade 3/4 anaemia, neutropenia and thrombocytopenia). We evaluated 2288 persons on BOC-, 409 on TPV-containing regimen and 6308 on PEG/RBV. Among these groups, respectively, 31%, 43% and 9% were treatment-experienced; 17%, 37% and 14% had baseline cirrhosis; 63%, 54% and 48% were genotype 1a. SVR rates among noncirrhotics were as follows: treatment naive: 65% (BOC), 67% (TPV) and 31% (PEG/RBV); treatment experienced: 57% (BOC), 54% (TPV) and 13% (PEG/RBV); (P-value not significant for BOC vs TPV; P < 0.0001 for BOC or TPV vs PEG/RBV). Haematologic toxicities among BOC-, TPV- and PEG/RBV-treated groups were as follows: grade 3/4 anaemia 7%, 11% and 3%; grade 4 thrombocytopenia 2.2%, 5.4% and 1.7%; grade 4 neutropenia 8.2%, 5.6% and 3.4%. SVR rates are higher and closer to those reported in pivotal clinical trials among BOC- and TPV-treated persons compared with PEG/RBV-treated persons. Haematologic adverse events are frequent, but severe toxicity is uncommon. C1 [Butt, A. A.; Yan, P.; Shaikh, O. S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Butt, A. A.; Shaikh, O. S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, A. A.] Hamad Med Corp, Doha, Qatar. [Freiberg, M. S.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Lo Re, V., III] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Justice, A. C.] Vet Affairs Healthcare Syst, West Haven, CT USA. [Justice, A. C.] Yale Univ, Sch Med, New Haven, CT USA. [Sherman, K. E.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. RP Butt, AA (reprint author), 3601 Fifth Ave,Suite 3A, Pittsburgh, PA 15213 USA. EM aabutt@pitt.edu RI Lo Re, Vincent/N-7817-2015; OI Butt, Adeel/0000-0002-1118-1826; Justice, Amy/0000-0003-0139-5502 FU National Institutes of Health: NIAAA [1U24AA020794, 1U01AA020790, U24AA022001]; NIMH [2P30MII062294]; NIAID [2 U01-A1069918]; NIDA [R01DA035616]; AHRQ [R01HS018372]; NCI [R01 CA173754] FX This work was supported by an investigator initiated grant by Merck Sharp and Dohme, Whitehouse Station, NJ. Study questions, data acquisition, data analysis and reporting were under the sole discretion of study investigators. Dr. Butt assumes all responsibility for the data presented in this paper. ACJ's time is supported by: National Institutes of Health: NIAAA (1U24AA020794, 1U01AA020790, U24AA022001), NIMH (2P30MII062294), NIAID (2 U01-A1069918), NIDA (R01DA035616), AHRQ (R01HS018372), NCI (R01 CA173754). NR 21 TC 6 Z9 6 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1352-0504 EI 1365-2893 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD SEP PY 2015 VL 22 IS 9 BP 691 EP 700 DI 10.1111/jvh.12375 PG 10 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA CM6RI UT WOS:000357816800002 PM 25524834 ER PT J AU Kjaer, T Degn, S Jensen, L Hansen, A Jensenius, J Le, L Sander, B Golas, M Pedersen, JS Andersen, G Thiel, S AF Kjaer, Troels Degn, Soren Jensen, Lisbeth Hansen, Annette Jensenius, Jens Le, Le Sander, Bjorn Golas, Monika Pedersen, Jan Skov Andersen, Gregers Thiel, Steffen TI Structural studies on complement activation by pattern recognition complexes SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 15th European Meeting on Complement in Human Disease (EMCHD) CY JUN 27-30, 2015 CL Uppsala, SWEDEN C1 [Kjaer, Troels; Jensen, Lisbeth; Hansen, Annette; Jensenius, Jens; Golas, Monika; Thiel, Steffen] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark. [Degn, Soren] Immune Dis Inst, Boston, MA USA. [Le, Le; Sander, Bjorn] Aarhus Univ, Dept Clin Med, DK-8000 Aarhus C, Denmark. [Sander, Bjorn; Golas, Monika] Aarhus Univ, Ctr Stochast Geometry & Adv Bioimaging CSGB, DK-8000 Aarhus C, Denmark. [Pedersen, Jan Skov] Aarhus Univ, Dept Chem, Interdisciplinary Nanosci Ctr INANO, DK-8000 Aarhus C, Denmark. [Andersen, Gregers] Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus C, Denmark. RI Pedersen, Jan/A-8346-2008 OI Pedersen, Jan/0000-0002-7768-0206 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD SEP PY 2015 VL 67 IS 1 SI SI MA 097 BP 152 EP 152 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA CL7HW UT WOS:000357144100110 ER PT J AU Zheng, X Zhang, XL Kang, A Ran, CZ Wang, GJ Hao, HP AF Zheng, Xiao Zhang, Xueli Kang, An Ran, Chongzhao Wang, Guangji Hao, Haiping TI Thinking outside the brain for cognitive improvement: Is peripheral immunomodulation on the way? SO NEUROPHARMACOLOGY LA English DT Review DE Cognitive decline; Neuroimmune interaction; Brain-gut axis; Peripheral targets; Gut microbiota; CNS drug discovery ID ADVANCE TRANSLATIONAL RESEARCH; CENTRAL-NERVOUS-SYSTEM; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASES; EXPERIMENTAL STROKE; PARKINSONS-DISEASE; TNF-ALPHA; GUT-BRAIN; T-CELLS AB Cognitive impairment is a devastating condition commonly observed with normal aging and neurodegenerative disorders such as Alzheimer's Disease (AD). Although major efforts to prevent or slow down cognitive decline are largely focused within the central nervous system (CNS), it has become clear that signals from the systemic milieu are closely associated with the dysfunctional brain. In particular, the bidirectional crosstalk between the CNS and peripheral immune system plays a decisive role in shaping neuronal survival and function via neuroimmune, neuroendocrinal and bioenergetic mechanisms. Importantly, it is emerging that some neuroprotective and cognition-strengthening drugs may work by targeting the brain-periphery interactions, which could be intriguingly achieved without entering the CNS. We describe here how recent advances in dissecting cognitive deficits from a systems-perspective have contributed to a non-neurocentric understanding of its pathogenesis and treatment strategy. We also discuss the therapeutic and diagnostic implications of these exciting progresses and consider some key issues in the clinical translation. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Zheng, Xiao] Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing 210029, Jiangsu, Peoples R China. [Zheng, Xiao; Wang, Guangji; Hao, Haiping] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Peoples R China. [Zhang, Xueli] Southeast Univ, Zhong Da Hosp, Nanjing 210009, Peoples R China. [Kang, An] Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Jiangsu, Peoples R China. [Ran, Chongzhao] Harvard Univ, Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Zheng, X (reprint author), Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing 210029, Jiangsu, Peoples R China. EM xiaozhengcpu@gmail.com; hhp_770505@hotmail.com OI Hao, Haiping/0000-0003-2522-7546 FU National Natural Science Foundation of China [81325025, 81202983]; Natural Science Foundation of Jiangsu province [BK20141035] FX This work is supported in part by funds from the National Natural Science Foundation of China (No. 81325025 and 81202983) and Natural Science Foundation of Jiangsu province (No. BK20141035). NR 146 TC 6 Z9 6 U1 5 U2 32 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 SEP PY 2015 VL 96 SI SI BP 94 EP 104 DI 10.1016/j.neuropharm.2014.06.020 PN A PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CN0KZ UT WOS:000358103800010 PM 24978103 ER PT J AU Forman, SA Chiara, DC Miller, KW AF Forman, Stuart A. Chiara, David C. Miller, Keith W. TI Anesthetics target interfacial transmembrane sites in nicotinic acetylcholine receptors SO NEUROPHARMACOLOGY LA English DT Review DE Alcohol; Propofol; Barbiturates; Allosterism; Photolabel; Mutagenesis ID GATED ION-CHANNEL; PROPOFOL BINDING-SITE; TORPEDO-CALIFORNICA; GENERAL-ANESTHETICS; ALLOSTERIC TRANSITIONS; GABA(A) RECEPTOR; GLYCINE RECEPTOR; RESTING STATE; NONCOMPETITIVE ANTAGONIST; HYDROPHOBIC INHIBITOR AB General anesthetics are a heterogeneous group of small amphiphilic ligands that interact weakly at multiple allosteric sites on many pentameric ligand gated ion channels (pLGICs), resulting in either inhibition, potentiation of channel activity, or both. Allosteric principles imply that modulator sites must change configuration and ligand affinity during receptor state transitions. Thus, general anesthetics and related compounds are useful both as state-dependent probes of receptor structure and as potentially selective modulators of pLGIC functions. This review focuses on general anesthetic sites in nicotinic acetylcholine receptors, which were among the first anesthetic-sensitive pLGIC experimental models studied, with particular focus on sites formed by transmembrane domain elements. Structural models place many of these sites at interfaces between two or more pLGIC transmembrane helices both within subunits and between adjacent subunits, and between transmembrane helices and either lipids (the lipid-protein interface) or water (i.e. the ion channel). A single general anesthetic may bind at multiple allosteric sites in pLGICs, producing a net effect of either inhibition (e.g. blocking the ion channel) or enhanced channel gating (e.g. inter-subunit sites). Other general anesthetic sites identified by photolabeling or crystallography are tentatively linked to functional effects, including intra-subunit helix bundle sites and the lipid-protein interface. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Forman, Stuart A.; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Forman, Stuart A.; Miller, Keith W.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Chiara, David C.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Jackson 444,55 Fruit St, Boston, MA 02114 USA. EM saforman@partners.org; david_chiara@hms.harvard.edu; kwmiller@mgh.harvard.edu FU National Institutes of Health [P01GM58448, R01GM89745]; NIGMS [P41-GM103311] FX This work was supported by grants from the National Institutes of Health (P01GM58448 to KWM and R01GM89745 to SAF). We thank Prof. Jonathan Cohen (Dept. of Neurobiology, Harvard Medical School, Boston, MA) for comments and help with molecular modeling. Chimera is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311). NR 99 TC 10 Z9 10 U1 0 U2 14 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 SEP PY 2015 VL 96 SI SI BP 169 EP 177 DI 10.1016/j.neuropharm.2014.10.002 PN B PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CN0LA UT WOS:000358103900005 PM 25316107 ER PT J AU Berg, KM Piper, ME Smith, SS Fiore, MC Jorenby, DE AF Berg, Kristin M. Piper, Megan E. Smith, Stevens S. Fiore, Michael C. Jorenby, Douglas E. TI Defining and predicting short-term alcohol use changes during a smoking cessation attempt SO ADDICTIVE BEHAVIORS LA English DT Article DE Tobacco use; Smoking cessation; Alcohol use ID NICOTINE DEPENDENCE; TOBACCO DEPENDENCE; DISTRESS TOLERANCE; UNITED-STATES; CONSUMPTION; ADDICTION; HEALTH; DRINKING; WITHDRAWAL; DISORDERS AB Introduction: Alcohol and nicotine are commonly used substances in the U.S., with significant impacts on health. Using both substances concurrently impacts quit attempts. While studies have sought to examine changes in alcohol use co-occurring with tobacco cessation, results have not been consistent. Understanding these changes has clinical implications. The objective of this study is to identify changes in alcohol consumption that occur following tobacco cessation, as well as predictors of alcohol use patterns following a smoking cessation attempt. Methods: A secondary analysis of a randomized, placebo-controlled trial evaluating the efficacy of five tobacco cessation pharmacotherapies. Participants (N = 1301) reported their smoking and alcohol consumption daily for two weeks prior to, and two weeks after, the target quit date (TQD). Results: Generally, alcohol use decreased post-TQD. Smokers who reported less pre-quit alcohol use, as well as smokers who were female, non-white, and had a history of alcohol dependence tended to use less alcohol post-quit. Pre- and post-quit alcohol use were more strongly related among men and among those without a history of alcohol dependence. Conclusions: For most smokers alcohol use decreased following smoking cessation. These results suggest that the expectation should be of decreased alcohol use post cessation. However, attention may be warranted for those who drink higher amounts of alcohol pre-cessation because they may be more likely to drink more in the post-quit period which may influence smoking cessation success. Published by Elsevier Ltd. C1 [Berg, Kristin M.; Piper, Megan E.; Smith, Stevens S.; Fiore, Michael C.; Jorenby, Douglas E.] Univ Wisconsin, Sch Med & Publ Hlth, Ctr Tobacco Res & Intervent, Dept Med, Madison, WI 53711 USA. [Berg, Kristin M.] William S Middleton Mem Vet Adm Med Ctr, Adv Fellowship Womens Hlth, Madison, WI 53705 USA. RP Berg, KM (reprint author), Ctr Tobacco Res & Intervent, 1930 Monroe St, Madison, WI 53711 USA. EM kberg@medicine.wisc.edu; mep@ctri.wisc.edu; Sss@ctri.wisc.edu; mcf@ctri.wisc.edu; dej@ctri.wisc.edu FU Training Tobacco Scientists Mini-Grant through the University of Wisconsin Center for Tobacco Research and Intervention - National Cancer Institute [9P50CA143188-11] FX This research was supported by the Training Tobacco Scientists Mini-Grant through the University of Wisconsin Center for Tobacco Research and Intervention, which is funded from grant 9P50CA143188-11 from the National Cancer Institute. The funding source did not have impact on the planning, design, analysis or interpretation of this secondary analysis. NR 46 TC 3 Z9 3 U1 0 U2 6 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 SEP PY 2015 VL 48 BP 52 EP 57 DI 10.1016/j.addbeh.2015.04.004 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA CL1WZ UT WOS:000356736900009 PM 25997014 ER PT J AU Fennessy, FM Fedorov, A Penzkofer, T Kim, KW Hirsch, MS Vangel, MG Masry, P Flood, TA Chang, MC Tempany, CM Mulkern, RV Gupta, SN AF Fennessy, Fiona M. Fedorov, Andriy Penzkofer, Tobias Kim, Kyung Won Hirsch, Michelle S. Vangel, Mark G. Masry, Paul Flood, Trevor A. Chang, Ming-Ching Tempany, Clare M. Mulkern, Robert V. Gupta, Sandeep N. TI Quantitative pharmacokinetic analysis of prostate cancer DCE-MRI at 3 T: comparison of two arterial input functions on cancer detection with digitized whole mount histopathological validation SO MAGNETIC RESONANCE IMAGING LA English DT Article DE Prostate cancer; Dynamic contrast enhancement; Arterial input function; Pharmacokinetic analysis ID CONTRAST-ENHANCED MRI; HUMAN BREAST-CANCER; MULTIPARAMETRIC MRI; PATHOLOGICAL STAGE; TUMOR VOLUME; PARAMETERS; PERFUSION; REPRODUCIBILITY; AGGRESSIVENESS; CARCINOMA AB Accurate pharmacokinetic (PK) modeling of dynamic contrast enhanced MRI (DCE-MRI) in prostate cancer (PCa) requires knowledge of the concentration time course of the contrast agent in the feeding vasculature, the so-called arterial input function (AIF). The purpose of this study was to compare AIF choice in differentiating peripheral zone PCa from non-neoplastic prostatic tissue (NNPT), using PK analysis of high temporal resolution prostate DCE-MRI data and whole-mount pathology (WMP) validation. This prospective study was performed in 30 patients who underwent multiparametric endorectal prostate MRI at 3.0 T and WMP validation. PCa foci were annotated on WMP slides and MR images using 3D Slicer. Foci >= 0.5 cm(3) were contoured as tumor regions of interest (TROIs) on subtraction DCE (early-arterial pre-contrast) images. PK analyses of TROI and NNPT data were performed using automatic AIF (aAlF) and model AIF (mAIF) methods. A paired t-test compared mean and 90th percentile (p90) PK parameters obtained with the two AIF approaches. Receiver operating characteristic (ROC) analysis determined diagnostic accuracy (DA) of PK parameters. Logistic regression determined correlation between PK parameters and histopathology. Mean TROI and NNPT PK parameters were higher using aAIF vs. mAIF (p < 0.05). There was no significant difference in DA between AIF methods: highest for p90 volume transfer constant (K-trans) (aAlF differences in the area under the ROC curve (Az) = 0.827; mAIF Az = 0.93). Tumor cell density correlated with aAIF Km's (p = 0.03). Our results indicate that DCE-MRI using both AIF methods is excellent in discriminating PCa from NNPT. If quantitative DCE-MRI is to be used as a biomarker in PCa, the same AIF method should be used consistently throughout the study. (C) 2015 Elsevier Inc. All rights reserved. C1 [Fennessy, Fiona M.; Fedorov, Andriy; Penzkofer, Tobias; Tempany, Clare M.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Fennessy, Fiona M.; Kim, Kyung Won] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Penzkofer, Tobias] RWTH Aachen Univ Hosp, Dept Radiol, Aachen, Germany. [Hirsch, Michelle S.; Masry, Paul; Flood, Trevor A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Vangel, Mark G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Chang, Ming-Ching; Gupta, Sandeep N.] Gen Elect Global Res, Niskayuna, NY 12309 USA. [Mulkern, Robert V.] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Fennessy, FM (reprint author), Dept Radiol, 45 Francis St, Boston, MA 02115 USA. EM ffennessy@partners.org OI Fedorov, Andrey/0000-0003-4806-9413 FU [U01CA151261]; [P4IEB015898]; [R01CA111288] FX U01CA151261, P4IEB015898, R01CA111288. NR 44 TC 6 Z9 6 U1 5 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X EI 1873-5894 J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD SEP PY 2015 VL 33 IS 7 BP 886 EP 894 DI 10.1016/j.mri.2015.02.008 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK9LL UT WOS:000356561500003 PM 25683515 ER PT J AU Crysel, LC Cook, CL Schember, TO Webster, GD AF Crysel, Laura C. Cook, Corey L. Schember, Tatiana Orozco Webster, Gregory D. TI Harry Potter and the measures of personality: Extraverted Gryffindors, agreeable Hufflepuffs, clever Ravenclaws, and manipulative Slytherins SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Dark Triad; Harry Potter; Psychopathy; Narcissism; Machiavellianism; Need for cognition; Need to belong; Big Five ID DARK TRIAD; DIRTY DOZEN; NEED; SELF; MACHIAVELLIANISM; TRANSPORTATION; PSYCHOPATHY; MOTIVATION; NARCISSISM; COGNITION AB People use fiction and storytelling to learn about themselves and their social world. Fans of J.K. Rowling's popular Harry Potter book series often identify with one of the four Hogwarts school communities or "houses"-Gryffindor, Hufflepuff, Ravenclaw, and Slytherin-that correspond to characters' specific traits. Fans use a feature on Rowling's "Pottermore" website that tests their personality and sorts them into the Hogwarts. house that best fits them. But what does Pottermore's sorting quiz measure? We asked fans from online Harry Potter groups into which Hogwarts house they had been sorted on Pottermore. Fans then completed personality measures, including the Big Five traits, need to belong, need for cognition, and the Dark Triad traits narcissism, Machiavellianism, and psychopathy. Planned contrasts found positive associations between need for cognition and placement in Ravenclaw (known for wit and learning), and between the Dark Triad traits and placement in Slytherin (known for using any means to achieve their ends). We expected but did not find that those in Gryffindor (known for bravery) would be higher in extraversion and openness, and that Hufflepuffs (known for loyalty) would be higher on need to belong. Our findings suggest that fiction can reflect real underlying personality dimensions. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Crysel, Laura C.] Stetson Univ, Deland, FL 32723 USA. [Cook, Corey L.] Univ Washington Tacoma, Tacoma, WA USA. [Schember, Tatiana Orozco] US Dept Vet Affairs, Tulsa, OK USA. [Webster, Gregory D.] Univ Florida, Gainesville, FL 32611 USA. RP Crysel, LC (reprint author), Stetson Univ, Deland, FL 32723 USA. EM lcrysel@stetson.edu NR 27 TC 0 Z9 0 U1 16 U2 75 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD SEP PY 2015 VL 83 BP 174 EP 179 DI 10.1016/j.paid.2015.04.016 PG 6 WC Psychology, Social SC Psychology GA CL0OQ UT WOS:000356642400031 ER PT J AU Amoozgar, Z Goldberg, MS AF Amoozgar, Zohreh Goldberg, Michael S. TI Targeting myeloid cells using nanoparticles to improve cancer immunotherapy SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE Cancer immunotherapy; Targeted nanoparticle delivery; Myeloid cells; Dendritic cells; Tumor-associated macrophages ID TUMOR-ASSOCIATED MACROPHAGES; ANTIGEN-PRESENTING CELLS; HUMAN DENDRITIC CELLS; POLY(GAMMA-GLUTAMIC ACID) NANOPARTICLES; DRAINING LYMPH-NODES; IN-VIVO; IMMUNE-RESPONSES; T-CELLS; ANTITUMOR IMMUNITY; DRUG-DELIVERY AB While nanoparticles have traditionally been used to deliver cytotoxic drugs directly to tumors to induce cancer cell death, emerging data suggest that nanoparticles are likely to generate a larger impact on oncology through the delivery of agents that can stimulate antitumor immunity. Tumor-targeted nanocarriers have generally been used to localize chemotherapeutics to tumors and thus decrease off-target toxicity while enhancing efficacy. Challengingly, tumor heterogeneity and evolution render tumor-intrinsic approaches likely to succumb to relapse. The immune system offers exquisite specificity, cytocidal potency, and long-term activity that leverage an adaptive memory response. For this reason, the ability to manipulate immune cell specificity and function would be desirable, and nanoparticles represent an exciting means by which to perform such manipulation. Dendritic cells and tumor-associated macrophages are cells of the myeloid lineage that function as natural phagocytes, so they naturally take up nanoparticles. Dendritic cells direct the specificity and potency of cellular immune responses that can be targeted for cancer vaccines. Herein, we discuss the specific criteria needed for efficient vaccine design, including but not limited to the route of administration, size, morphology, surface charge, targeting ligands, and nanoparticle composition. In contrast, tumor-associated macrophages are critical mediators of immunosuppression whose trans-migratory abilities can be exploited to localize therapeutics to the tumor core and which can be directly targeted for elimination or for repolarization to a tumor suppressive phenotype. It is likely that a combination of targeting dendritic cells to stimulate antitumor immunity and tumor-associated macrophages to reduce immune suppression will impart significant benefits and result in durable antitumor responses. (C) 2014 Elsevier B.V. All rights reserved. C1 [Goldberg, Michael S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA. RP Goldberg, MS (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. EM michael.goldberg1@dfci.harvard.edu FU Aid for Cancer Research (ACR); Cancer Research Institute (CRI); Melanoma Research Alliance (MRA); Ovarian Cancer Research Fund (OCRF) FX The authors would like to thank Aid for Cancer Research (ACR) for its financial support of Dr. Amoozgar (ACR fellow) as well as the Cancer Research Institute (CRI), Melanoma Research Alliance (MRA), and Ovarian Cancer Research Fund (OCRF) for their support of Dr. Goldberg. NR 135 TC 13 Z9 13 U1 16 U2 75 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X EI 1872-8294 J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD AUG 30 PY 2015 VL 91 BP 38 EP 51 DI 10.1016/j.addr.2014.09.007 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CS2VF UT WOS:000361929400005 PM 25280471 ER PT J AU Hofmann, SG Fang, A Brager, DN AF Hofmann, Stefan G. Fang, Angela Brager, Daniel N. TI Effect of intranasal oxytocin administration on psychiatric symptoms: A meta-analysis of placebo-controlled studies SO PSYCHIATRY RESEARCH LA English DT Article DE Oxytocin; Therapy; Depression; Anxiety; Autism; Psychosis ID OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; SOCIAL ANXIETY DISORDER; NEGATIVE SYMPTOMS; RATING-SCALE; DOUBLE-BLIND; SCHIZOPHRENIA; BEHAVIOR; HUMANS; AUTISM AB Clinical trials of intranasal administration of oxytocin for treating psychiatric problems have yielded mixed results. To conduct a quantitative review of placebo-controlled clinical trials of intranasally-administered oxytocin (OT) for psychiatric symptoms, manual and electronic searches using PubMed and PsycINFO were conducted. Of 1828 entries, 16 placebo-controlled studies totaling 330 participants were included in the analysis. The overall placebo-controlled effect size was moderately strong (Hedges' g=0.67) and robust as suggested by the fail-safe N and funnel plot analysis. OT reduced symptoms of depression, anxiety, autism/repetitive behaviors, psychotic symptoms, and general psychopathology. In the combined sample, symptom reduction was moderated by frequency of administration. Publication year and diagnostic category did not moderate the effect of OT on the clinical outcome measures. We conclude that intranasal administration of OT is a potentially useful intervention for reducing psychiatric symptoms. However, more studies are needed to determine the best treatment target and to identify the mechanism of treatment change. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Hofmann, Stefan G.; Brager, Daniel N.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Fang, Angela] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Hofmann, SG (reprint author), Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. EM shofmann@bu.edu RI Hofmann, Stefan/B-8769-2014; OI Hofmann, Stefan/0000-0002-3548-9681; Fang, Angela/0000-0002-7666-9988 FU NCCIH NIH HHS [R01 AT007257, R01AT007257]; NIMH NIH HHS [R34 MH086668, K23 MH100259, K23MH100259, R01 MH099021, R01MH099021, R21 MH101567, R21 MH102646, R21MH101567, R21MH102646, R34 MH099311, R34MH086668, R34MH099311] NR 54 TC 10 Z9 10 U1 2 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 30 PY 2015 VL 228 IS 3 BP 708 EP 714 DI 10.1016/j.psychres.2015.05.039 PG 7 WC Psychiatry SC Psychiatry GA CP9YI UT WOS:000360251400069 PM 26094200 ER PT J AU Darrow, SM Illmann, C Gauvin, C Osiecki, L Egan, CA Greenberg, E Eckfield, M Hirschtritt, ME Pauls, DL Batterson, JR Berlin, CM Malaty, IA Woods, DW Scharf, JM Mathews, CA AF Darrow, Sabrina M. Illmann, Cornelia Gauvin, Caitlin Osiecki, Lisa Egan, Crystelle A. Greenberg, Erica Eckfield, Monika Hirschtritt, Matthew E. Pauls, David L. Batterson, James R. Berlin, Cheston M. Malaty, Irene A. Woods, Douglas W. Scharf, Jeremiah M. Mathews, Carol A. TI Web-based phenotyping for Tourette Syndrome: Reliability of common co-morbid diagnoses SO PSYCHIATRY RESEARCH LA English DT Article DE Tourette Syndrome; Obsessive-compulsive disorder; Attention deficit/hyperactivity disorder; Web-based assessment ID OBSESSIVE-COMPULSIVE DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CROSS-DISORDER; TIC DISORDERS; SCALE; PREVALENCE; AGREEMENT; SEVERITY; FAMILY; ADHD AB Collecting phenotypic data necessary for genetic analyses of neuropsychiatric disorders is time consuming and costly. Development of web-based phenotype assessments would greatly improve the efficiency and cost-effectiveness of genetic research. However, evaluating the reliability of this approach compared to standard, in-depth clinical interviews is essential. The current study replicates and extends a preliminary report on the utility of a web-based screen for Tourette Syndrome (TS) and common comorbid diagnoses (obsessive compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD)). A subset of individuals who completed a web-based phenotyping assessment for a TS genetic study was invited to participate in semi-structured diagnostic clinical interviews. The data from these interviews were used to determine participants' diagnostic status for TS, OCD, and ADHD using best estimate procedures, which then served as the gold standard to compare diagnoses assigned using web-based screen data. The results show high rates of agreement for TS. Kappas for OCD and ADHD diagnoses were also high and together demonstrate the utility of this self-report data in comparison previous diagnoses from clinicians and dimensional assessment methods. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Darrow, Sabrina M.; Eckfield, Monika; Hirschtritt, Matthew E.; Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Illmann, Cornelia; Gauvin, Caitlin; Osiecki, Lisa; Greenberg, Erica; Pauls, David L.; Scharf, Jeremiah M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA 02114 USA. [Egan, Crystelle A.] Northern Calif VA Hlth Care Syst, Martinez Outpatient Clin, Martinez, CA 94553 USA. [Egan, Crystelle A.] Northern Calif VA Hlth Care Syst, Community Living Ctr, Martinez, CA 94553 USA. [Eckfield, Monika] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Eckfield, Monika] Calif State Univ East Bay, Dept Nursing & Hlth Sci, Hayward, CA 94542 USA. [Batterson, James R.] Univ Missouri, Kansas City Sch Med, Childrens Mercy Hosp & Clin, Kansas City, MO 64108 USA. [Berlin, Cheston M.] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Hershey, PA 17033 USA. [Malaty, Irene A.] Univ Florida, Coll Med, Dept Neurol, UF Ctr Movement Disorders & Neurorestorat, Gainesville, FL 32607 USA. [Woods, Douglas W.] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Scharf, Jeremiah M.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Scharf, Jeremiah M.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Mathews, CA (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave,Box F-0984, San Francisco, CA 94143 USA. EM cmathews@lppi.ucsf.edu FU National Institutes of Health [R01MH096767, U01NS040024, K23MH085057, K02MH00508, R01NS016648]; Tourette Syndrome Association FX This work was supported by the National Institutes of Health, Grant numbers R01MH096767 ("Refining the Tourette syndrome phenotype across diagnoses to aid gene discovery," PI: Carol Mathews), U01NS040024 ("A genetic linkage study of GTS," PI: David Pauls), K23MH085057 ("Translational phenomics and genomics of Gilles de la Tourette syndrome," PI: Jeremiah Scharf), K02MH00508 ("Genetics of a behavioral disorder: Tourette syndrome," PI: David Pauls), and R01NS016648 ("A genetic study of GTS, OCD, and ADHD," PI: David Pauls), and from the Tourette Syndrome Association. NR 34 TC 2 Z9 2 U1 4 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 30 PY 2015 VL 228 IS 3 BP 816 EP 825 DI 10.1016/j.psychres.2015.05.017 PG 10 WC Psychiatry SC Psychiatry GA CP9YI UT WOS:000360251400086 PM 26054936 ER PT J AU Kimbrel, NA Flynn, EJ Stephanie, G Carpenter, J Cammarata, CM Leto, F Ostiguy, WJ Kamholz, BW Zimering, RT Gulliver, SB AF Kimbrel, Nathan A. Flynn, Elisa J. Stephanie, Grace Carpenter, J. Cammarata, Claire M. Leto, Frank Ostiguy, William J. Kamholz, Barbara W. Zimering, Rose T. Gulliver, Suzy B. TI Internal consistency, test-retest reliability, and predictive validity for a Likert-based version of the Sources of occupational stress-14 (SOOS-14) scale SO PSYCHIATRY RESEARCH LA English DT Article DE Stress; PTSD; Depression ID FIREFIGHTERS; DEPRESSION AB This study examined the psychometric properties of a Likert-based version of the Sources of Occupational Stress-14 (SOOS-14) scale. Internal consistency for the SOOS-14 ranged from 0.78-0.84, whereas three-month test-retest reliability was 0.51. In addition, SOOS-14 scores were prospectively associated with symptoms of PTSD and depression at a three-month follow-up assessment. Published by Elsevier Ireland Ltd. C1 [Kimbrel, Nathan A.] Durham Vet Affairs Med Ctr, Durham, NC 27705 USA. [Kimbrel, Nathan A.] VA Midatlantic Mental Illness Res Educ & Clin Ctr, Durham, NC USA. [Kimbrel, Nathan A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Flynn, Elisa J.; Stephanie, Grace; Gulliver, Suzy B.] Baylor Scott & White Warriors Res Inst, Waco, TX USA. [Flynn, Elisa J.; Stephanie, Grace; Gulliver, Suzy B.] Texas A&M Univ, Hlth Sci Ctr, Dept Psychiat & Behav Sci, College Stn, TX USA. [Cammarata, Claire M.; Leto, Frank] New York City Fire Dept, Counseling Serv Unit, New York, NY USA. [Ostiguy, William J.] Boston Fire Dept, Boston, MA USA. [Kamholz, Barbara W.; Zimering, Rose T.] VA Boston Healthcare Syst, Boston, MA USA. [Kamholz, Barbara W.; Zimering, Rose T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Kimbrel, NA (reprint author), Durham Vet Affairs Med Ctr, 508 Fulton St, Durham, NC 27705 USA. EM Nathan.Kimbrel@va.gov RI Kimbrel, Nathan/P-3109-2016 OI Kimbrel, Nathan/0000-0001-7218-1005 FU Federal Emergency Management Agency (FEMA) [EMW2010FP00597]; Clinical Science Research and Development Service of the Department of Veterans Affairs Office of Research and Development [IK2 CX000525] FX This research was supported by a Federal Emergency Management Agency (FEMA) Award (EMW2010FP00597) to Dr. Gulliver entitled "Motivational Intervention to Maximize Peer Behavioral Health Awareness and Skills." Dr. Kimbrel was supported by a Career Development Award (IK2 CX000525) from the Clinical Science Research and Development Service of the Department of Veterans Affairs Office of Research and Development. Special thanks to Cindy Zavodny, Amruta Mardikar, Marty Sonnenberg, Erin Hart, Firefighter Andrew Kane, Firefighter Joseph Scaramuzzino, Firefighter David Gettens, Captain Rudy Weindler, Firefighter Joe Lennon, Captain Mike Sorrentino, Lieutenant Kirk Lester, Focus Suites of New York, the WAC of Miami, and the International Association of Fire Fighters. 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, FEMA, or the United States government. NR 6 TC 0 Z9 0 U1 0 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 30 PY 2015 VL 228 IS 3 BP 961 EP 962 DI 10.1016/j.psychres.2015.05.031 PG 2 WC Psychiatry SC Psychiatry GA CP9YI UT WOS:000360251400111 PM 26073282 ER PT J AU Cheraghi-Sohi, S Singh, H Reeves, D Stocks, J Rebecca, M Esmail, A Campbell, S de Wet, C AF Cheraghi-Sohi, Sudeh Singh, Hardeep Reeves, David Stocks, Jill Rebecca, Morris Esmail, Aneez Campbell, Stephen de Wet, Carl TI Missed diagnostic opportunities and English general practice: a study to determine their incidence, confounding and contributing factors and potential impact on patients through retrospective review of electronic medical records (vol 10, 105, 2015) SO IMPLEMENTATION SCIENCE LA English DT Correction C1 [Cheraghi-Sohi, Sudeh; Stocks, Jill; Rebecca, Morris; Esmail, Aneez; Campbell, Stephen] Univ Manchester, NIHR Greater Manchester Primary Care Patient Safe, Manchester M13 9PL, Lancs, England. [Cheraghi-Sohi, Sudeh; Reeves, David; Rebecca, Morris; Esmail, Aneez; Campbell, Stephen] Univ Manchester, Inst Populat Hlth, Ctr Primary Care, Manchester M13 9PL, Lancs, England. [Singh, Hardeep] Houston Vet Affairs Ctr Innovat Qual Effectivenes, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, Houston, TX 77030 USA. [Campbell, Stephen] Univ Canberra, Ctr Res & Act Publ Hlth CeRAPH, Bruce, ACT 2617, Australia. [de Wet, Carl] Griffith Univ, Sch Med, Nathan, Qld 4111, Australia. RP Campbell, S (reprint author), Univ Manchester, NIHR Greater Manchester Primary Care Patient Safe, 7th Floor,Williamson Bldg, Manchester M13 9PL, Lancs, England. EM stephen.campbell@manchester.ac.uk FU NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre; Houston VA Health Services Research and Development Service Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX The authors acknowledge the contribution of Dr Rahul Alam and Angela Swallow. The research was funded by the NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Dr. Singh is partially supported by the Houston VA Health Services Research and Development Service Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). NR 2 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 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD AUG 29 PY 2015 VL 10 AR 124 DI 10.1186/s13012-015-0314-1 PG 1 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CQ0BU UT WOS:000360260900001 PM 26319233 ER PT J AU Li, D Shao, L Chen, BC Zhang, X Zhang, MS Moses, B Milkie, DE Beach, JR Hammer, JA Pasham, M Kirchhausen, T Baird, MA Davidson, MW Xu, PY Betzig, E AF Li, Dong Shao, Lin Chen, Bi-Chang Zhang, Xi Zhang, Mingshu Moses, Brian Milkie, Daniel E. Beach, Jordan R. Hammer, John A., III Pasham, Mithun Kirchhausen, Tomas Baird, Michelle A. Davidson, Michael W. Xu, Pingyong Betzig, Eric TI Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics SO SCIENCE LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; LIVING CELLS; LIVE CELLS; FLUORESCENCE MICROSCOPY; CELLULAR STRUCTURES; OPTICAL NANOSCOPY; PLASMA-MEMBRANE; ACTIN DYNAMICS; F-ACTIN; PROTEIN AB Super-resolution fluorescence microscopy is distinct among nanoscale imaging tools in its ability to image protein dynamics in living cells. Structured illumination microscopy (SIM) stands out in this regard because of its high speed and low illumination intensities, but typically offers only a twofold resolution gain. We extended the resolution of live-cell SIM through two approaches: ultrahigh numerical aperture SIM at 84-nanometer lateral resolution for more than 100 multicolor frames, and nonlinear SIM with patterned activation at 45- to 62-nanometer resolution for approximately 20 to 40 frames. We applied these approaches to image dynamics near the plasma membrane of spatially resolved assemblies of clathrin and caveolin, Rab5a in early endosomes, and a-actinin, often in relationship to cortical actin. In addition, we examined mitochondria, actin, and the Golgi apparatus dynamics in three dimensions. C1 [Li, Dong; Shao, Lin; Chen, Bi-Chang; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA 20147 USA. [Zhang, Xi; Zhang, Mingshu; Xu, Pingyong] Chinese Acad Sci, Key Lab RNA Biol, Beijing 100101, Peoples R China. [Zhang, Xi; Zhang, Mingshu; Xu, Pingyong] Chinese Acad Sci, Beijing Key Lab Noncoding RNA, Inst Biophys, Beijing 100101, Peoples R China. [Zhang, Xi] Cent China Normal Univ, Coll Life Sci, Wuhan 430079, Hubei, Peoples R China. [Moses, Brian; Milkie, Daniel E.] Coleman Technol, Newtown Sq, PA 19073 USA. [Beach, Jordan R.; Hammer, John A., III; Baird, Michelle A.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Pasham, Mithun; Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol & Pediat, Boston, MA 02115 USA. [Pasham, Mithun; Kirchhausen, Tomas] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Baird, Michelle A.; Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. [Baird, Michelle A.; Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32310 USA. RP Betzig, E (reprint author), Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA. EM betzige@janelia.hhmi.org RI Chen , Bi-Chang /F-3480-2014 FU Howard Hughes Medical Institute (HHMI); National Basic Research Program (973 Program) of China [2013CB910103]; National Natural Science Foundation of China [31370851]; Beijing Natural Science Foundation, China [7131011]; NIH [GM-075252] FX We thank the Shared Resource teams at Janelia for their skill and dedication in specimen handling and preparation and the Instrument Design and Fabrication team for their manufacturing expertise. D.L., L.S., B.-C.C., and E.B. are funded by the Howard Hughes Medical Institute (HHMI). X.Z., M.Z., and P.X. are funded by the National Basic Research Program (973 Program) of China (2013CB910103), the National Natural Science Foundation of China (31370851), and the Beijing Natural Science Foundation, China (7131011). M.P. and T.K. were funded in part by NIH grant GM-075252. Skylan-NS is available from P.X. upon execution of a materials transfer agreement with the Institute of Biophysics. Other fluorescent protein constructs used in this work are from the Michael Davidson Collection and are available, along with sequence information, from Addgene (www.addgene.org/fluorescent-proteins/davidson). Researchers can apply to access the microscope as visitors through the Advanced Imaging Center at Janelia (www.janelia.org/open-science/advanced-imaging-center). Technical information for the construction of a copy of the microscope is available to nonprofit entities upon execution of a no-cost Research License with HHMI. Nonlinear SIM with patterned activation, in two or three dimensions, as described here is covered within U.S. provisional patent application 62/057,220 filed by E.B. and D.L. and assigned to HHMI. NR 53 TC 78 Z9 81 U1 78 U2 192 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 AUG 28 PY 2015 VL 349 IS 6251 AR aab3500 DI 10.1126/science.aab3500 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ5LW UT WOS:000360646800044 PM 26315442 ER PT J AU Singh, T Gupta, NA Xu, S Prasad, R Velu, SE Katiyar, SK AF Singh, Tripti Gupta, Nirzari A. Xu, Su Prasad, Ram Velu, Sadanandan E. Katiyar, Santosh K. TI Honokiol inhibits the growth of head and neck squamous cell carcinoma by targeting epidermal growth factor receptor SO ONCOTARGET LA English DT Article DE oncology; carcinogenesis; chemotherapy; targeted therapy; signal transduction; prevention; animal model ID IN-VIVO; BCL-2 FAMILY; CANCER; APOPTOSIS; PROTEIN; DEATH; REGULATORS; SURVIVAL; THERAPY; CYCLINS AB Here, we report the chemotherapeutic effect of honokiol, a phytochemical from Magnolia plant, on human head and neck squamous cell carcinoma (HNSCC). Treatment of HNSCC cell lines from different sub-sites, SCC-1 (oral cavity), SCC-5 (larynx), OSC-19 (tongue) and FaDu (pharynx) with honokiol inhibited their cell viability, which was associated with the: (i) induction of apoptosis, (ii) correction of dysregulatory cell cycle proteins of G0/G1 phase. Honokiol decreased the expression levels of epidermal growth factor receptor (EGFR), mTOR and their downstream signaling molecules. Treatment of FaDu and SCC-1 cell lines with rapamycin, an inhibitor of mTOR pathway, also reduced cell viability of HNSCC cells. Administration of honokiol by oral gavage (100 mg/kg body weight) significantly (P < 0.01-0.001) inhibited the growth of SCC-1 and FaDu xenografts in athymic nude mice, which was associated with: (i) inhibition of tumor cell proliferation, (ii) induction of apoptosis, (iii) reduced expressions of cyclins and Cdks, and (iv) inhibition of EGFR signaling pathway. Molecular docking analysis of honokiol in EGFR binding site indicated that the chemotherapeutic effect of honokiol against HNSCC is mediated through its firm binding with EGFR, which is better than that of gefitinib, a commonly used drug for HNSCC treatment. C1 [Singh, Tripti; Prasad, Ram; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Gupta, Nirzari A.; Xu, Su; Velu, Sadanandan E.] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA. [Velu, Sadanandan E.; Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu RI Xu, Su/S-3631-2016 OI Xu, Su/0000-0002-3695-5605 FU Veterans Administration Merit Review Award [1I01BX001410-01] FX This work was financially supported by the funds from the Veterans Administration Merit Review Award (1I01BX001410-01, S.K.K.). The content of this manuscript does not necessarily reflect the views or policies of the funding agency. NR 32 TC 12 Z9 13 U1 2 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 AUG 28 PY 2015 VL 6 IS 25 BP 21268 EP 21282 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9XO UT WOS:000360969200045 PM 26020804 ER PT J AU Yamada, Y Eto, M Ito, Y Mochizuki, S Son, BK Ogawa, S Iijima, K Kaneki, M Kozaki, K Toba, K Akishita, M Ouchi, Y AF Yamada, Yoko Eto, Masato Ito, Yuki Mochizuki, Satoru Son, Bo-Kyung Ogawa, Sumito Iijima, Katsuya Kaneki, Masao Kozaki, Koichi Toba, Kenji Akishita, Masahiro Ouchi, Yasuyoshi TI Suppressive Role of PPAR gamma-Regulated Endothelial Nitric Oxide Synthase in Adipocyte Lipolysis SO PLOS ONE LA English DT Article ID NONALCOHOLIC FATTY LIVER; INSULIN-RESISTANCE; S-NITROSYLATION; DISEASE; EXPRESSION; OBESITY; GENE; MICE; DIET; STEATOHEPATITIS AB Introduction Metabolic syndrome causes insulin resistance and is associated with risk factor clustering, thereby increasing the risk of atherosclerosis. Recently, endothelial nitric oxide synthase deficient (eNOS-/-) mice have been reported to show metabolic disorders. Interestingly, eNOS has also been reported to be expressed in non-endothelial cells including adipocytes, but the functions of eNOS in adipocytes remain unclear. Methods and Results The eNOS expression was induced with adipocyte differentiation and inhibition of eNOS/NO enhanced lipolysis in vitro and in vivo. Furthermore, the administration of a high fat diet (HFD) was able to induce non-alcoholic steatohepatitis (NASH) in eNOS-/- mice but not in wild type mice. A PPAR. antagonist increased eNOS expression in adipocytes and suppressed HFD-induced fatty liver changes. Conclusions eNOS-/- mice induce NASH development, and these findings provide new insights into the therapeutic approach for fatty liver disease and related disorders. C1 [Yamada, Yoko; Eto, Masato; Ito, Yuki; Mochizuki, Satoru; Son, Bo-Kyung; Ogawa, Sumito; Iijima, Katsuya; Akishita, Masahiro; Ouchi, Yasuyoshi] Univ Tokyo, Dept Geriatr Med, Grad Sch Med, Tokyo, Japan. [Kaneki, Masao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,Shriners Hos, Boston, MA USA. [Kozaki, Koichi; Toba, Kenji] Kyorin Univ, Sch Med, Dept Geriatr Med, Tokyo, Japan. RP Eto, M (reprint author), Univ Tokyo, Dept Geriatr Med, Grad Sch Med, Tokyo, Japan. EM meto-tky@umin.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology; Japan Society for the Promotion of Science (JSPS) FX This work was supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology (to M.E.) and by a Grant-in-Aid for Japan Society for the Promotion of Science (JSPS) Fellows (to Y.Y.). NR 36 TC 1 Z9 1 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 28 PY 2015 VL 10 IS 8 AR e0136597 DI 10.1371/journal.pone.0136597 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ0PO UT WOS:000360299100107 PM 26317347 ER PT J AU Hinson, JT Chopra, A Nafissi, N Polacheck, WJ Benson, CC Swist, S Gorham, J Yang, L Schafer, S Sheng, CC Haghighi, A Homsy, J Hubner, N Church, G Cook, SA Linke, WA Chen, CS Seidman, JG Seidman, CE AF Hinson, John T. Chopra, Anant Nafissi, Navid Polacheck, William J. Benson, Craig C. Swist, Sandra Gorham, Joshua Yang, Luhan Schafer, Sebastian Sheng, Calvin C. Haghighi, Alireza Homsy, Jason Hubner, Norbert Church, George Cook, Stuart A. Linke, Wolfgang A. Chen, Christopher S. Seidman, J. G. Seidman, Christine E. TI Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy SO SCIENCE LA English DT Article ID MESENCHYMAL STEM-CELLS; CARDIAC MICROTISSUES; DIFFERENTIATION; CARDIOMYOCYTES; HYPERTROPHY; FORCE AB Human mutations that truncate the massive sarcomere protein titin [TTN-truncating variants (TTNtvs)] are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtvs, diminish contractile performance and are pathogenic. By combining functional analyses with RNA sequencing, we explain why truncations in the A-band domain of TTN cause DCM, whereas truncations in the I band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS cell-derived cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and beta-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodeling. C1 [Hinson, John T.; Haghighi, Alireza; Seidman, Christine E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Chopra, Anant; Polacheck, William J.; Chen, Christopher S.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Chopra, Anant; Polacheck, William J.; Yang, Luhan; Church, George; Chen, Christopher S.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Nafissi, Navid; Gorham, Joshua; Yang, Luhan; Sheng, Calvin C.; Haghighi, Alireza; Homsy, Jason; Church, George; Seidman, J. G.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Benson, Craig C.] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA. [Swist, Sandra; Linke, Wolfgang A.] Ruhr Univ Bochum, Dept Cardiovasc Physiol, D-44780 Bochum, Germany. [Schafer, Sebastian; Hubner, Norbert] Max Delbruck Ctr Mol Med, Cardiovasc & Metab Sci, Berlin, Germany. [Haghighi, Alireza; Seidman, Christine E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Hubner, Norbert] DZHK German Ctr Cardiovasc Res, Berlin, Germany. [Cook, Stuart A.] Univ London Imperial Coll Sci Technol & Med, Royal Brompton & Harefield Natl Hlth Serv NHS Tru, Biomed Res Unit Cardiovasc Dis, Natl Inst Hlth Res NIHR, London, England. [Cook, Stuart A.] Natl Heart Ctr, Singapore, Singapore. [Cook, Stuart A.] Duke Natl Univ, Singapore, Singapore. RP Hinson, JT (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM jthinson@partners.org; cseidman@genetics.med.harvard.edu OI Polacheck, William/0000-0003-2728-0746 FU LaDue Fellowship; American Heart Association; Sarnoff Foundation; Leducq Foundation; German Research Foundation [SFB 1002 TPB3]; NIH [HG005550, EB017103, HL115553, HL007374, HL125807]; NIHR Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust; RESBIO Technology Resource for Polymeric Biomaterials; Howard Hughes Medical Institute; Illumina, Inc. FX We thank M. von Frieling-Salewsky for titin gels and Innolign Biomedical for CMTs. This work was supported in part by grants from the LaDue Fellowship (J.T.H., J.H.), the American Heart Association (A.C.), the Sarnoff Foundation (N.N., C.C.S.), the Leducq Foundation (S.A.C., N.H., S.S., J.G.S., C.E.S.), the German Research Foundation [W.A.L. (SFB 1002 TPB3)], the NIH [L.Y. and G.C. (HG005550), C.S.C. (EB017103 and HL115553), C.C.B. (HL007374), J.T.H. (HL125807), C.E.S., and J.G.S.], the NIHR Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust (S.A.C.), the RESBIO Technology Resource for Polymeric Biomaterials (C.S.C.), and Howard Hughes Medical Institute (C.E.S., A.H.). C.E.S. and J.G.S. are cofounders of and own shares in Myokardia Inc., a company that is developing therapeutics for cardiomyopathies. C.S.C. is a cofounder of and owns equity in Innolign Biomedical, a company that is developing an organ-on-chip platform (based on the device used in this study) for measuring forces of cardiac microtissues. S.A.C. is a paid consultant for Illumina, Inc. NR 20 TC 53 Z9 54 U1 7 U2 27 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 AUG 28 PY 2015 VL 349 IS 6251 BP 982 EP 986 DI 10.1126/science.aaa5458 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ5LW UT WOS:000360646800055 PM 26315439 ER PT J AU Konishi, M Erdem, SS Weissleder, R Lichtman, AH McCarthy, JR Libby, P AF Konishi, Masanori Erdem, S. Sibel Weissleder, Ralph Lichtman, Andrew H. McCarthy, Jason R. Libby, Peter TI Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis SO CIRCULATION RESEARCH LA English DT Article DE dexamethasone; granzyme; immunology; molecular imaging; myocarditis ID CARDIOVASCULAR MAGNETIC-RESONANCE; DIFFERENTIATION AB Rationale: The development of molecular imaging approaches that assess specific immunopathologic mechanisms can advance the study of myocarditis. Objective: This study validates a novel molecular imaging tool that enables the in vivo visualization of granzyme B activity, a major effector of cytotoxic CD8(+) T lymphocytes. Methods and Results: We synthesized and optimized a fluorogenic substrate capable of reporting on granzyme B activity and examined its specificity ex vivo in mice hearts with experimental cytotoxic CD8(+) T lymphocyte-mediated myocarditis using fluorescence reflectance imaging, validated by histological examination. In vivo experiments localized granzyme B activity in hearts with acute myocarditis monitored by fluorescent molecular tomography in conjunction with coregistered computed tomography imaging. A model anti-inflammatory intervention (dexamethasone administration) in vivo reduced granzyme B activity (vehicle versus dexamethasone: 504263 versus 194 +/- 77 fluorescence intensities in hearts; P=0.002). Conclusions: Molecular imaging of granzyme B activity can visualize T cell-mediated myocardial injury and monitor the response to an anti-inflammatory intervention. C1 [Konishi, Masanori; Libby, Peter] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Lichtman, Andrew H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pathol, Boston, MA 02115 USA. [Konishi, Masanori; Libby, Peter] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Erdem, S. Sibel; Weissleder, Ralph; McCarthy, Jason R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02115 USA. [Erdem, S. Sibel] Istanbul Medipol Univ, Int Sch Med, Istanbul, Turkey. RP Libby, P (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, 77 Ave Louis Pasteur,NRB 741, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu FU National Institutes of Health National Heart, Lung, and Blood Institute contract [HHSN268201000044C, R01HL121363-01]; National Institutes of Health; Translational Program of Excellence in Nanotechnology; Japan Society for the Promotion of Science; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation; Uehara Memorial Foundation FX This study was supported, in part, by National Institutes of Health National Heart, Lung, and Blood Institute contract HHSN268201000044C and R01HL121363-01, Grant-in-Aid for Scientific Research from the National Institutes of Health; Translational Program of Excellence in Nanotechnology, Japan Society for the Promotion of Science; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation, and The Uehara Memorial Foundation; Research Fellowship. NR 21 TC 2 Z9 2 U1 0 U2 1 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 AUG 28 PY 2015 VL 117 IS 6 BP 502 EP 512 DI 10.1161/CIRCRESAHA.115.306364 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA CP8KG UT WOS:000360142000006 PM 26199323 ER PT J AU Jin, BR Lin, M You, ML Zong, YJ Wan, MX Xu, F Duan, ZF Lu, TJ AF Jin, Birui Lin, Min You, Minli Zong, Yujin Wan, Mingxi Xu, Feng Duan, Zhenfeng Lu, Tianjian TI Microbubble embedded with upconversion nanoparticles as a bimodal contrast agent for fluorescence and ultrasound imaging SO NANOTECHNOLOGY LA English DT Article DE ultrasound; microbubbles; bimodal contrast agent; upconversion; layer-by-layer self-assembly ID DRUG-DELIVERY; THERAPY; DESTRUCTION; DIRECTIONS AB Bimodal imaging offers additional imaging signal thus finds wide spread application in clinical diagnostic imaging. Fluorescence/ultrasound bimodal imaging contrast agent using fluorescent dyes or quantum dots for fluorescence signal has emerged as a promising method, which however requires visible light or UV irradiation resulting in photobleaching, photoblinking, auto-fluorescence and limited tissue penetration depth. To surmount these problems, we developed a novel bimodal contrast agent using layer-by-layer assembly of upconversion nanoparticles onto the surface of microbubbles. The resulting microbubbles with average size of 2 mu m provide enhanced ultrasound echo for ultrasound imaging and upconversion emission upon near infrared irradiation for fluorescence imaging. The developed bimodal contrast agent holds great potential to be applied in ultrasound target technique for targeted diseases diagnostics and therapy. C1 [Jin, Birui] Xi An Jiao Tong Univ, State Key Lab Mech Behav Mat, Xian 710049, Peoples R China. [Jin, Birui; Lin, Min; You, Minli; Xu, Feng; Lu, Tianjian] Xi An Jiao Tong Univ, Bioinspired Engn & Biomech Ctr BEBC, Xian 710049, Peoples R China. [Lin, Min; You, Minli; Zong, Yujin; Wan, Mingxi; Xu, Feng] Xi An Jiao Tong Univ, MOE Key Lab Biomed Informat Engn, Xian 710049, Peoples R China. [Lin, Min; Duan, Zhenfeng] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Jin, BR (reprint author), Xi An Jiao Tong Univ, State Key Lab Mech Behav Mat, Xian 710049, Peoples R China. EM minlin@mail.xjtu.edu.cn; tjlu@mail.xjtu.edu.cn RI Xu, Feng/C-7430-2011; Lu, Tian Jian/E-6063-2016; Xu, Feng/H-4468-2011 OI Xu, Feng/0000-0003-4351-0222 FU International Science and Technology Cooperation Program of China [2013DFG02930]; National Key Scientific Apparatus Development of Special Item [2013YQ190467]; Fundamental Research Funds for the Central Universities [2012jdhz46]; China Scholarship of Council FX This work was financially supported by the International Science and Technology Cooperation Program of China (2013DFG02930), National Key Scientific Apparatus Development of Special Item (2013YQ190467), and the Fundamental Research Funds for the Central Universities (2012jdhz46). M L is supported by a scholarship from the China Scholarship of Council. The TEM work was done at the International Center for Dielectric Research (ICDR), Xi'an Jiaotong University, Xi'an, China. The authors also thank Dai Yan Zhu, Lu Lu, and Ma Chuan Sheng for their help using TEM. NR 40 TC 1 Z9 2 U1 6 U2 39 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0957-4484 EI 1361-6528 J9 NANOTECHNOLOGY JI Nanotechnology PD AUG 28 PY 2015 VL 26 IS 34 AR 345601 DI 10.1088/0957-4484/26/34/345601 PG 8 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Science & Technology - Other Topics; Materials Science; Physics GA CO3SK UT WOS:000359079500014 PM 26243035 ER PT J AU Fondell, E O'Reilly, EJ Fitzgerald, KC Falcone, GJ Kolonel, LN Park, Y Gapstur, SM Ascherio, A AF Fondell, Elinor O'Reilly, EIlis J. Fitzgerald, Kathryn C. Falcone, Guido J. Kolonel, Laurence N. Park, Yikyung Gapstur, Susan M. Ascherio, Alberto TI Intakes of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis: Results from five cohort studies SO Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration LA English DT Article DE Amyotrophic lateral sclerosis; motor neuron disease; caffeine; epidemiology; longitudinal cohort studies ID FOOD-FREQUENCY QUESTIONNAIRE; HEALTH-AMERICAN-ASSOCIATION; SOCIETY CANCER PREVENTION; BASE-LINE CHARACTERISTICS; RETIRED-PERSONS DIET; PARKINSONS-DISEASE; NATIONAL-INSTITUTES; MULTIETHNIC COHORT; CONSUMPTION; WOMEN AB Caffeine is thought to be neuroprotective by antagonizing the adenosine A(2A) receptors in the brain and thereby protecting motor neurons from excitotoxicity. We examined the association between consumption of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis (ALS).Longitudinal analyses based on over 1,010,000 males and females in five large cohort studies (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study). Cohort-specific multivariable-adjusted risk ratios (RR) and 95% confidence intervals (CI) estimates of ALS incidence or death were estimated by Cox proportional hazards regression and pooled using random-effects models. Results showed that a total of 1279 cases of ALS were documented during a mean of 18 years of follow-up. Caffeine intake was not associated with ALS risk; the pooled multivariable-adjusted RR comparing the highest to the lowest quintile of intake was 0.96 (95% CI 0.81-1.16). Similarly, neither coffee nor tea was associated with ALS risk. In conclusion, the results of this large study do not support associations of caffeine or caffeinated beverages with ALS risk. C1 [Fondell, Elinor; O'Reilly, EIlis J.; Fitzgerald, Kathryn C.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Falcone, Guido J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Falcone, Guido J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Park, Yikyung] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA. [Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA. RP Fondell, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM efondell@hsph.harvard.edu RI Falcone, Guido/L-2287-2016 OI Falcone, Guido/0000-0002-6407-0302 FU ALS Therapy Alliance; National Cancer Institute FX This work was supported by grants from the ALS Therapy Alliance and the National Cancer Institute. NR 37 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD AUG 27 PY 2015 VL 16 IS 5-6 BP 366 EP 371 DI 10.3109/21678421.2015.1020813 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CV7TG UT WOS:000364477400012 PM 25822002 ER PT J AU Dascenco, D Erfurth, ML Izadifar, A Song, MM Sachse, S Bortnick, R Urwyler, O Petrovic, M Ayaz, D He, HH Kise, Y Thomas, F Kidd, T Schmucker, D AF Dascenco, Dan Erfurth, Maria-Luise Izadifar, Azadeh Song, Minmin Sachse, Sonja Bortnick, Rachel Urwyler, Olivier Petrovic, Milan Ayaz, Derya He, Haihuai Kise, Yoshiaki Thomas, Franziska Kidd, Thomas Schmucker, Dietmar TI Slit and Receptor Tyrosine Phosphatase 69D Confer Spatial Specificity to Axon Branching via Dscam1 SO CELL LA English DT Article ID DROSOPHILA-DSCAM; MOLECULAR DIVERSITY; SENSORY NEURONS; SELF-AVOIDANCE; PROTEIN; GUIDANCE; MIDLINE; REPELLENT; ISOFORMS; NEURITES AB Axonal branching contributes substantially to neuronal circuit complexity. Studies in Drosophila have shown that loss of Dscam1 receptor diversity can fully block axon branching in mechanosensory neurons. Here we report that cell-autonomous loss of the receptor tyrosine phosphatase 69D (RPTP69D) and loss of midline-localized Slit inhibit formation of specific axon collaterals through modulation of Dscam1 activity. Genetic and biochemical data support a model in which direct binding of Slit to Dscam1 enhances the interaction of Dscam1 with RPTP69D, stimulating Dscam1 dephosphorylation. Single-growth-cone imaging reveals that Slit/RPTP69D are not required for general branch initiation but instead promote the extension of specific axon collaterals. Hence, although regulation of intrinsic Dscam1-Dscam1 isoform interactions is essential for formation of all mechanosensory-axon branches, the local ligand-induced alterations of Dscam1 phosphorylation in distinct growth-cone compartments enable the spatial specificity of axon collateral formation. C1 [Dascenco, Dan; Erfurth, Maria-Luise; Izadifar, Azadeh; Sachse, Sonja; Urwyler, Olivier; Petrovic, Milan; Ayaz, Derya; He, Haihuai; Kise, Yoshiaki; Schmucker, Dietmar] VIB, Neuronal Wiring Lab, B-3000 Leuven, Belgium. [Dascenco, Dan; Erfurth, Maria-Luise; Izadifar, Azadeh; Sachse, Sonja; Urwyler, Olivier; Petrovic, Milan; Kise, Yoshiaki; Schmucker, Dietmar] Univ Leuven, Sch Med, Dept Oncol, B-3000 Leuven, Belgium. [Erfurth, Maria-Luise] Univ Kiel, Inst Biochem, D-24098 Kiel, Germany. [Song, Minmin; Kidd, Thomas] Univ Nevada, Biol MS 314, Reno, NV 89557 USA. [Sachse, Sonja] Free Univ Berlin, Dept Biol Chem & Pharm, D-14195 Berlin, Germany. [Bortnick, Rachel; Thomas, Franziska] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Schmucker, D (reprint author), VIB, Neuronal Wiring Lab, Herestr 49, B-3000 Leuven, Belgium. EM dietmar.schmucker@vib-kuleuven.be OI Kidd, Thomas/0000-0001-7190-4208 FU NIH [2RO1NS046747-05A1, 2P40OD010949-10A1]; FWO [G059611N, G078913N, G077013N]; BELSPO IUAP VII-20 "WIBRAIN''; VIB funding; Boehringer Ingelheim Fonds; EMBO; JSPS; SNSF; NSF [IOS-1052555]; National Center for Research Resources [P20RR016464, 5P20RR024210]; NIGM from the NIH [8 P20 GM103554]; DSHB; HFSP FX This work was supported by NIH (2RO1NS046747-05A1) (D.S.); FWO (G059611N) (D.S.); FWO (G078913N) (D.S.); FWO (G077013N) (D.S.); BELSPO IUAP VII-20 "WIBRAIN'' (D.S.); VIB funding; and fellowships of FWO (D.D.), Boehringer Ingelheim Fonds (M.-L.E. and S.S.), EMBO (M.P.), JSPS & HFSP (Y.K.), and SNSF (O.U.). The work of T.K. and M.S. was supported by NSF (IOS-1052555), the National Center for Research Resources (P20RR016464, 5P20RR024210), and the NIGM (8 P20 GM103554) from the NIH. We thank Tineke Breynaert for technical help (cell culture). We thank members of the lab, Paul Garrity (Brandeis University), Fritz Rathjen (MDC, Berlin), Bassem Hassan, Matthew Holt, and Georg Halder (VIB) for critical reading, discussions, and insightful comments. We would like to thank the Clemens, Bashaw, Dickson, Zinn, Suzuki, Treisman, Lee, Hassan, Kidd, and Bogdan labs for fly stocks, antibodies, and plasmids. For cell lines and antibodies, we thank the DGRC, supported by NIH grant 2P40OD010949-10A1, and the DSHB, created by the NICHD of the NIH and maintained by the university of Iowa. NR 46 TC 9 Z9 9 U1 1 U2 8 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 AUG 27 PY 2015 VL 162 IS 5 BP 1140 EP 1154 DI 10.1016/j.cell.2015.08.003 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CQ4QO UT WOS:000360589900022 PM 26317474 ER PT J AU Tan, L Akahane, K McNally, R Reyskens, KMSE Ficarro, SB Liu, SH Herter-Sprie, GS Koyama, S Pattison, MJ Labella, K Johannessen, L Akbay, EA Wong, KK Frank, DA Marto, JA Look, TA Arthur, JSC Eck, MJ Gray, NS AF Tan, Li Akahane, Koshi McNally, Randall Reyskens, Kathleen M. S. E. Ficarro, Scott B. Liu, Suhu Herter-Sprie, Grit S. Koyama, Shohei Pattison, Michael J. Labella, Katherine Johannessen, Liv Akbay, Esra A. Wong, Kwok-Kin Frank, David A. Marto, Jarrod A. Look, Thomas A. Arthur, J. Simon C. Eck, Michael J. Gray, Nathanael S. TI Development of Selective Covalent Janus Kinase 3 Inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; JAK-STAT PATHWAY; LUNG-CANCER; MYELOPROLIFERATIVE NEOPLASMS; IRREVERSIBLE INHIBITORS; RHEUMATOID-ARTHRITIS; DRUG DISCOVERY; CELL LYMPHOMA; BA/F3 CELLS; POTENT AB The Janus kinases (JAKs) and their downstream effectors, signal transducer and activator of transcription proteins (STATs), form a critical immune cell signaling circuit, which is of fundamental importance in innate immunity, inflammation, and hematopoiesis, and dysregulation is frequently observed in immune disease and cancer. The high degree of structural conservation of the JAK ATP binding pockets has posed a considerable challenge to medicinal chemists seeking to develop highly selective inhibitors as pharmacological probes and as clinical drugs. Here we report the discovery and optimization of 2,4-substituted pyrimidines as covalent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Investigation of structure activity relationship (SAR) utilizing biochemical and transformed Ba/F3 cellular assays resulted in identification of potent and selective inhibitors such as compounds 9 and 45. A 2.9 angstrom cocrystal structure of JAK3 in complex with 9 confirms the covalent interaction. Compound 9 exhibited decent pharmacokinetic properties and is suitable for use in vivo. These inhibitors provide a set of useful tools to pharmacologically interrogate JAK3-dependent biology. C1 [Tan, Li; McNally, Randall; Ficarro, Scott B.; Johannessen, Liv; Marto, Jarrod A.; Eck, Michael J.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Tan, Li; McNally, Randall; Ficarro, Scott B.; Johannessen, Liv; Marto, Jarrod A.; Eck, Michael J.; Gray, Nathanael S.] Dana Farber Canc Inst, Longwood Ctr, Dept Canc Biol, Boston, MA 02215 USA. [Akahane, Koshi; Look, Thomas A.] Dana Farber Canc Inst, Longwood Ctr, Dept Pediat Oncol, Boston, MA 02215 USA. [Liu, Suhu; Herter-Sprie, Grit S.; Koyama, Shohei; Labella, Katherine; Akbay, Esra A.; Wong, Kwok-Kin; Frank, David A.] Dana Farber Canc Inst, Longwood Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Reyskens, Kathleen M. S. E.; Pattison, Michael J.; Arthur, J. Simon C.] Univ Dundee, Coll Life Sci, Div Cell Signaling & Immunol, Dundee DD1 5EH, Scotland. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM nathanael_gray@dfci.harvard.edu OI Pattison, Michael/0000-0001-7588-2560; Koyama, Shohei/0000-0002-6897-9417 FU Deutsche Forschungsgemeinschaft [HE 6897/1-1] FX We thank Dr. Cai-Hong Yun for his valuable help with creating topology and parameter files for the refinement of the JAK3-9 cocrystal structure. The TEL-JAK1, TEL-JAK2, TEL-JAK3, and TEL-ABL plasmids used in this studies were generously provided by Dr. Richard Moriggl. G.S.H.-S. was supported by the Deutsche Forschungsgemeinschaft (HE 6897/1-1). We thank Dr. Ying Li for data analysis and Dr. Sara Buhrlage for the proofreading. NR 79 TC 16 Z9 17 U1 6 U2 30 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 AUG 27 PY 2015 VL 58 IS 16 BP 6589 EP 6606 DI 10.1021/acs.jmedchem.5b00710 PG 18 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CQ2FQ UT WOS:000360415800021 PM 26258521 ER PT J AU Kiely, AP Ling, H Asi, YT Kara, E Proukakis, C Schapira, AH Morris, HR Roberts, HC Lubbe, S Limousin, P Lewis, PA Lees, AJ Quinn, N Hardy, J Love, S Revesz, T Houlden, H Holton, JL AF Kiely, Aoife P. Ling, Helen Asi, Yasmine T. Kara, Eleanna Proukakis, Christos Schapira, Anthony H. Morris, Huw R. Roberts, Helen C. Lubbe, Steven Limousin, Patricia Lewis, Patrick A. Lees, Andrew J. Quinn, Niall Hardy, John Love, Seth Revesz, Tamas Houlden, Henry Holton, Janice L. TI Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation SO MOLECULAR NEURODEGENERATION LA English DT Article DE Parkinson's disease; Multiple system atrophy; alpha-synuclein; Clinical features; Phosphorylation; Mutation; SNCA ID MULTIPLE-SYSTEM ATROPHY; ALPHA-SYNUCLEIN AGGREGATION; FAMILIAL PARKINSONS-DISEASE; BRAIN PATHOLOGY; MEMBRANE-BINDING; FIBRIL FORMATION; LEWY BODIES; DEMENTIA; E46K; NEURODEGENERATION AB Background: We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson's disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case. Results: All three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural hypotension and transiently levodopa responsive parkinsonism. Detailed post-mortem neuropathological analysis was performed in all cases. All three G51D cases had abundant alpha-synuclein pathology with characteristics of both PD and MSA. These included widespread cortical and subcortical neuronal alpha-synuclein inclusions together with small numbers of inclusions resembling glial cytoplasmic inclusions (GCIs) in oligodendrocytes. In contrast the H50Q and SNCA duplication cases, had alpha-synuclein pathology resembling idiopathic PD without GCIs. Phosphorylated alpha-synuclein was present in all inclusions types in G51D cases but was more restricted in SNCA duplication and H50Q mutation. Inclusions were also immunoreactive for the 5G4 antibody indicating their highly aggregated and likely fibrillar state. Conclusions: Our characterisation of the clinical and neuropathological features of the present small series of G51D SNCA mutation cases should aid the recognition of this clinico-pathological entity. The neuropathological features of these cases consistently share characteristics of PD and MSA and are distinct from PD patients carrying the H50Q or SNCA duplication. C1 [Kiely, Aoife P.; Ling, Helen; Asi, Yasmine T.; Lees, Andrew J.; Hardy, John; Revesz, Tamas; Holton, Janice L.] UCL Inst Neurol, Dept Mol Neurosci, Queen Sq Brain Bank, London WC1N 3BG, England. [Lewis, Patrick A.; Lees, Andrew J.; Hardy, John; Houlden, Henry] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Lewis, Patrick A.; Lees, Andrew J.; Hardy, John; Houlden, Henry] UCL Inst Neurol, Reta Lila Weston Inst Neurol Studies, London WC1N 3BG, England. [Limousin, Patricia] UCL, Sobell Dept Motor Neurosci & Movement Disorders, Unit Funct Neurosurg, UCL Inst Neurol, London, England. [Lewis, Patrick A.] Univ Reading, Sch Pharm, Reading, Berks, England. [Proukakis, Christos; Schapira, Anthony H.; Morris, Huw R.; Lubbe, Steven] UCL Inst Neurol, Dept Clin Neurosci, London WC1N 3BG, England. [Roberts, Helen C.] Univ Southampton, Acad Geriatr Med, Southampton, Hants, England. [Quinn, Niall] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [Love, Seth] Univ Bristol, Clin Neurosci, Bristol, Avon, England. [Kara, Eleanna] Harvard Univ, Sch Med, Alzheimers Dis Res Ctr, Charlestown, MA 02129 USA. [Kara, Eleanna] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Holton, JL (reprint author), UCL Inst Neurol, Dept Mol Neurosci, Queen Sq Brain Bank, Queen Sq, London WC1N 3BG, England. EM janice.holton@ucl.ac.uk RI Hardy, John/C-2451-2009; Roberts, Helen/A-5551-2016; Lubbe, Steven/L-8261-2013; Morris, Huw/B-8527-2008; Houlden, Henry/C-1532-2008; Revesz, Tamas/A-8732-2010; OI Roberts, Helen/0000-0002-5291-1880; Morris, Huw/0000-0002-5473-3774; Houlden, Henry/0000-0002-2866-7777; Revesz, Tamas/0000-0003-2501-0259; Lewis, Patrick/0000-0003-4537-0489 FU Parkinson's UK (PUK); Multiple System Atrophy (MSA) Trust; Progressive Supranuclear Palsy (Europe) Association; Cortico Basal Degeneration (CBD) Solutions; Alzheimer's Research UK; Michael J Fox Foundation; Reta Lila Weston Insitute for Neurological Studies; Medical Research Council UK; MSA Trust; CBD Solutions; Government of Kuwait; PUK [8047, J1101]; Medical Research Council (MRC) UK [G0700943, G1100643]; MRC UK [MR/L010933/1]; MRC; Dystonia Medical Research Foundation (DMRF); Parkinson's disease foundation; PUK; NIHR Biomedical Research Unit in Dementia based at University College London Hospitals (UCLH), University College London (UCL); Wellcome Trust/MRC [WT089698]; National Institute for Health Research University College London Hospitals Biomedical Research Centre FX JLH and AJL are supported by Parkinson's UK (PUK), the Multiple System Atrophy (MSA) Trust and the Progressive Supranuclear Palsy (Europe) Association. TR and JH are supported by Cortico Basal Degeneration (CBD) Solutions. JLH is supported by Alzheimer's Research UK, the Michael J Fox Foundation. Queen Square Brain Bank is supported by Reta Lila Weston Insitute for Neurological Studies and the Medical Research Council UK. APK is supported by the MSA Trust. HL is supported by a CBD Solutions research grant and employed by Reta Lila Weston Institute of Neurological Studies. YTA is supported by the Government of Kuwait. HRM and SL are funded by PUK (Grants 8047 and J1101) and the Medical Research Council (MRC) UK (G0700943, G1100643). PAL is a PUK research fellow (F1002) and is supported by a New Investigator Research Grant from the MRC UK (MR/L010933/1). HH is supported by the MRC, the Dystonia Medical Research Foundation (DMRF) and the Parkinson's disease foundation. AHS is supported by PUK and is a National Institute for Health research (NIHR) senior investigator. The research was in part funded by the NIHR Biomedical Research Unit in Dementia based at University College London Hospitals (UCLH), University College London (UCL). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This work was supported in part by the Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to the UK Parkinson's Disease Consortium (UKPDC) whose members are from the UCL Institute of Neurology, the University of Sheffield and the MRC protein Phosphorylation Unit at the University of Dundee. This research was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. NR 70 TC 5 Z9 5 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD AUG 27 PY 2015 VL 10 AR 41 DI 10.1186/s13024-015-0038-3 PG 17 WC Neurosciences SC Neurosciences & Neurology GA CQ0CE UT WOS:000360261900001 PM 26306801 ER PT J AU Powe, NR Peterson, PG Mark, EJ AF Powe, Neil R. Peterson, P. Gabriel Mark, Eugene J. TI Case 27-2015: A 78-Year-Old Man with Hypercalcemia and Renal Failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LYMPH-NODE BIOPSY; MULTIPLE-MYELOMA; SARCOIDOSIS; CANCER C1 [Powe, Neil R.] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. [Powe, Neil R.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. [Peterson, P. Gabriel] Walter Reed Natl Mil Med Ctr, Dept Radiol, Bethesda, MD USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Powe, NR (reprint author), San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. NR 13 TC 0 Z9 0 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 27 PY 2015 VL 373 IS 9 BP 864 EP 873 DI 10.1056/NEJMcpc1310003 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CP8VC UT WOS:000360171700013 PM 26308688 ER PT J AU Gantz, SC Robinson, BG Buck, DC Bunzow, JR Neve, RL Williams, JT Neve, KA AF Gantz, Stephanie C. Robinson, Brooks G. Buck, David C. Bunzow, James R. Neve, Rachael L. Williams, John T. Neve, Kim A. TI Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium SO ELIFE LA English DT Article ID VENTRAL TEGMENTAL AREA; PROTEIN-COUPLED RECEPTOR; HAMSTER OVARY CELLS; UP-REGULATION; IMPULSE ACTIVITY; MESSENGER-RNA; LONG RECEPTOR; MICE LACKING; 2 ISOFORMS; KINASE-C AB D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent G protein-coupled inwardly rectifying potassium (GIRK) currents. The results reveal that D2S, but not D2L receptors, exhibited calciumdependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors. C1 [Gantz, Stephanie C.; Robinson, Brooks G.; Bunzow, James R.; Williams, John T.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA. [Buck, David C.; Neve, Kim A.] US Dept Vet Affairs, Res Serv, VA Portland Hlth Care Syst, Portland, OR 97204 USA. [Buck, David C.; Neve, Kim A.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Neve, Rachael L.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Neve, KA (reprint author), US Dept Vet Affairs, Res Serv, VA Portland Hlth Care Syst, Portland, OR 97204 USA. EM nevek@ohsu.edu FU National Institutes of Health [P50 DA018165, R01 DA004523, R01 DA034388, F32 DA038456]; U.S. Department of Veterans Affairs [BX000810] FX National Institutes of Health P50 DA018165 Kim A Neve; U.S. Department of Veterans Affairs BX000810 Kim A Neve; National Institutes of Health R01 DA004523 John T Williams; National Institutes of Health R01 DA034388 John T Williams; National Institutes of Health F32 DA038456 Brooks G Robinson NR 60 TC 4 Z9 4 U1 0 U2 1 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD AUG 26 PY 2015 VL 4 AR e09358 DI 10.7554/eLife.09358.001 PG 19 WC Biology SC Life Sciences & Biomedicine - Other Topics GA DI9JK UT WOS:000373818700001 ER PT J AU Sundaresan, TK Haber, DA AF Sundaresan, Tilak K. Haber, Daniel A. TI Does molecular monitoring matter in early-stage breast cancer? SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID CIRCULATING TUMOR DNA; DISEASE C1 [Sundaresan, Tilak K.; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. [Sundaresan, Tilak K.; Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. EM dhaber@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD AUG 26 PY 2015 VL 7 IS 302 AR 302fs35 DI 10.1126/scitranslmed.aac9445 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CQ9NQ UT WOS:000360942300002 PM 26311727 ER PT J AU McFarland, LV AF McFarland, Lynne V. TI Application of meta-analysis to specific research fields: Lessons learned SO WORLD JOURNAL OF META-ANALYSIS LA English DT Editorial Material DE Meta-analysis; Study designs; Probiotics; Sensitivity analysis; Meta-regression ID ANTIBIOTIC-ASSOCIATED DIARRHEA; RANDOMIZED CONTROLLED-TRIALS; PROBIOTICS; PREVENTION; CHILDREN; DISEASE; THERAPY; LIPIDS; RISK AB Scientific research is challenged to translate findings from multiple, often conflicting, clinical trials into a simple answer of whether a treatment works or not. The public and healthcare providers alike frequently voice their frustrations when the media reports a treatment working on one day, but seemingly the next day reports a study refuting the previous one. Meta-analyses are being used more commonly by researchers to convey an understandable summary of scientific studies to the general public and healthcare providers. As time goes by, we have learned how to improve meta-analytic techniques to reflect more valid results and when it is appropriate to pool or not to pool results from different studies. Retrospective reviews often don't acknowledge this learning curve and may fail to recommend the most current valid guidelines. This editorial presents an example of how the current use of meta-analysis has shifted in one field (the therapeutic effects of probiotics) and recommendations on how to correctly interpret the results of such an analysis. C1 [McFarland, Lynne V.] Univ Washington, Dept Med Chem, Seattle, WA 98108 USA. [McFarland, Lynne V.] VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. RP McFarland, LV (reprint author), VA Puget Sound Healthcare Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM lynne.mcfarland@va.gov NR 30 TC 2 Z9 2 U1 0 U2 0 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 2308-3840 J9 WORLD J META-ANAL JI World J. Meta-Anal. PD AUG 26 PY 2015 VL 3 IS 4 BP 188 EP 192 DI 10.13105/wjma.v3.i4.188 PG 5 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA CR0GG UT WOS:000360995900001 ER PT J AU He, Q Zhu, Y Corbin, BA Plagge, A Bastepe, M AF He, Qing Zhu, Yan Corbin, Braden A. Plagge, Antonius Bastepe, Murat TI The G protein alpha subunit variant XL alpha(s) promotes inositol 1,4,5-trisphosphate signaling and mediates the renal actions of parathyroid hormone in vivo SO SCIENCE SIGNALING LA English DT Article ID PROXIMAL TUBULE CELLS; VITAMIN-D METABOLISM; GNAS LOCUS; TRANSIENT PSEUDOHYPOPARATHYROIDISM; PTH/PTHRP RECEPTOR; GROWTH-RETARDATION; COUPLED RECEPTORS; POSTNATAL-GROWTH; PHOSPHOLIPASE-C; ACTIVATION AB GNAS, which encodes the stimulatory G protein (heterotrimeric guanine nucleotide-binding protein) a subunit (G alpha(s)), also encodes a large variant of G alpha(s) termed extra-large a subunit (XL alpha(s)), and alterations in XL alpha(s) abundance or activity are implicated in various human disorders. Although XL alpha(s), like G alpha(s), stimulates generation of the second messenger cyclic adenosine monophosphate (cAMP), evidence suggests that XL alpha(s) and G alpha(s) have opposing effects in vivo. We investigated the role of XL alpha(s) in mediating signaling by parathyroid hormone (PTH), which activates a G protein-coupled receptor (GPCR) that stimulates both G alpha(s) and G alpha(q/11) in renal proximal tubules to maintain phosphate and vitamin D homeostasis. At postnatal day 2 (P2), XL alpha(s) knockout (XLKO) mice exhibited hyperphosphatemia, hypocalcemia, and increased serum concentrations of PTH and 1,25-dihydroxyvitamin D. The ability of PTH to reduce serum phosphate concentrations was impaired, and the abundance of the sodium phosphate cotransporter Npt2a in renal brush border membranes was reduced in XLKO mice, whereas PTH-induced cAMP excretion in the urine was modestly increased. Basal and PTH-stimulated production of inositol 1,4,5-trisphosphate (IP3), which is the second messenger produced by G alpha(q/11) signaling, was repressed in renal proximal tubules from XLKO mice. Crossing of XLKO mice with mice overexpressing XL alpha(s) specifically in renal proximal tubules rescued the phenotype of the XLKO mice. Overexpression of XL alpha(s) in HEK 293 cells enhanced IP3 generation in unstimulated cells and in cells stimulated with PTH or thrombin, which acts through a G(q/11)-coupled receptor. Together, our findings suggest that XL alpha(s) enhances G(q/11) signaling to mediate the renal actions of PTH during early postnatal development. C1 [He, Qing; Zhu, Yan; Corbin, Braden A.; Bastepe, Murat] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [He, Qing; Zhu, Yan; Corbin, Braden A.; Bastepe, Murat] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Plagge, Antonius] Univ Liverpool, Dept Cellular & Mol Physiol, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu FU Harvard Catalyst: The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH Award) [UL1 TR001102]; Harvard University; NIH/National Institute of Diabetes and Digestive and Kidney Diseases [RO1DK073911]; NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [P30 AR066261]; Harvard Catalyst: The Harvard Clinical and Translational Science Center (National Center for Research Resources) [UL1 TR001102] FX This work was conducted with support from Harvard Catalyst: The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. The studies were funded in part by a research grant from NIH/National Institute of Diabetes and Digestive and Kidney Diseases (RO1DK073911 to M.B.). The MGH Endocrine Unit Center for Skeletal Research was funded by a grant from NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30 AR066261). NR 59 TC 4 Z9 4 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD AUG 25 PY 2015 VL 8 IS 391 AR ra84 DI 10.1126/scisignal.aaa9953 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CQ7UC UT WOS:000360809100002 PM 26307011 ER PT J AU Wilhelmsen, K Xu, FY Farrar, K Tran, A Khakpour, S Sundar, S Prakash, A Wang, JH Gray, NS Hellman, J AF Wilhelmsen, Kevin Xu, Fengyun Farrar, Katherine Tran, Alphonso Khakpour, Samira Sundar, Shirin Prakash, Arun Wang, Jinhua Gray, Nathanael S. Hellman, Judith TI Extracellular signal-regulated kinase 5 promotes acute cellular and systemic inflammation SO SCIENCE SIGNALING LA English DT Article ID ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; EPIDERMAL-GROWTH-FACTOR; HUMAN ENDOTHELIAL-CELLS; KRUPPEL-LIKE FACTOR-2; C-JUN PROMOTER; SHEAR-STRESS; MAP KINASE; PROSTATE-CANCER; ERK5 ACTIVATION AB Inflammatory critical illness is a syndrome that is characterized by acute inflammation and organ injury, and it is triggered by infections and noninfectious tissue injury, both of which activate innate immune receptors and pathways. Although reports suggest an anti-inflammatory role for the mitogen-activated protein kinase ( MAPK) extracellular signal-regulated kinase 5 (ERK5), we previously found that ERK5 mediates proinflammatory responses in primary human cells in response to stimulation of Toll-like receptor 2 (TLR2). We inhibited the kinase activities and reduced the abundances of ERK5 and MEK5, a MAPK kinase directly upstream of ERK5, in primary human vascular endothelial cells and monocytes, and found that ERK5 promoted inflammation induced by a broad range of microbial TLR agonists and by the proinflammatory cytokines interleukin1-beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). Furthermore, we found that inhibitors of MEK5 or ERK5 reduced the plasma concentrations of proinflammatory cytokines in mice challenged with TLR ligands or heat-killed Staphylococcus aureus, as well as in mice that underwent sterile lung ischemia-reperfusion injury. Finally, we found that inhibition of ERK5 protected endotoxemic mice from death. Together, our studies support a proinflammatory role for ERK5 in primary human endothelial cells and monocytes, and suggest that ERK5 is a potential therapeutic target in diverse disorders that cause inflammatory critical illness. C1 [Wilhelmsen, Kevin; Xu, Fengyun; Tran, Alphonso; Sundar, Shirin; Prakash, Arun; Hellman, Judith] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Farrar, Katherine; Khakpour, Samira] Univ Calif San Francisco, Grad Program Biomed Sci, San Francisco, CA 94143 USA. [Wang, Jinhua; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Hellman, Judith] Univ Calif San Francisco, Div Crit Care Med, San Francisco, CA 94143 USA. [Hellman, Judith] Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. RP Wilhelmsen, K (reprint author), Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. EM wilhelmsenk@anesthesia.ucsf.edu FU UCSF Department of Anesthesia; National Science Foundation Graduate Research Fellowship Program [1144247]; San Francisco Foundation; Linde Program in Chemical Biology FX This work was supported by the UCSF Department of Anesthesia, the National Science Foundation Graduate Research Fellowship Program (#1144247), and the San Francisco Foundation. The Gray laboratory acknowledges the support of the Linde Program in Chemical Biology. NR 130 TC 1 Z9 1 U1 4 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD AUG 25 PY 2015 VL 8 IS 391 AR ra86 DI 10.1126/scisignal.aaa3206 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CQ7UC UT WOS:000360809100004 PM 26307013 ER PT J AU Prust, MJ Jafari-Khouzani, K Kalpathy-Cramer, J Polaskova, P Batchelor, TT Gerstner, ER Dietrich, J AF Prust, Morgan J. Jafari-Khouzani, Kourosh Kalpathy-Cramer, Jayashree Polaskova, Pavlina Batchelor, Tracy T. Gerstner, Elizabeth R. Dietrich, Jorg TI Standard chemoradiation for glioblastoma results in progressive brain volume loss SO NEUROLOGY LA English DT Article ID CEREBRAL WHITE-MATTER; ADJUVANT CHEMOTHERAPY; BREAST-CANCER; COGNITIVE DEFICITS; SURVIVORS; LYMPHOMA; DYSFUNCTION; IMPAIRMENT; CARCINOMA; THERAPY AB Objective: To investigate the effects of chemotherapy and cranial irradiation on normal brain tissue using in vivo neuroimaging in patients with glioblastoma. Methods: We used longitudinal MRI to monitor structural brain changes during standard treatment in patients newly diagnosed with glioblastoma. We assessed volumetric and diffusion tensor imaging measures in 14 patients receiving 6 weeks of chemoradiation, followed by up to 6 months of temozolomide chemotherapy alone. We examined changes in whole brain, gray matter (GM), white matter (WM), anterior lateral ventricle, and hippocampal volumes. Normal-appearing GM, WM, and hippocampal analyses were conducted within the hemisphere of lowest/absent tumor burden. We examined diffusion tensor imaging measures within the subventricular zone. Results: Whole brain (F = 2.41; p = 0.016) and GM (F = 2.13; p = 0.036) volume decreased during treatment, without significant WM volume change. Anterior lateral ventricle volume increased significantly (F = 65.51; p < 0.001). In participants analyzed beyond 23 weeks, mean ventricular volume increased by 42.2% (SE: 8.8%; t = 4.94; p < 0.005). Apparent diffusion coefficient increased within the subventricular zone (F = 7.028; p < 0.001). No significant changes were identified in hippocampal volume. Conclusions: We present evidence of significant and progressive treatment-associated structural brain changes in patients with glioblastoma treated with standard chemoradiation. Future studies using longitudinal neuropsychological evaluation are needed to characterize the functional consequences of these structural changes. C1 [Prust, Morgan J.; Dietrich, Jorg] Harvard Univ, Sch Med, Boston, MA 02138 USA. [Prust, Morgan J.; Jafari-Khouzani, Kourosh; Kalpathy-Cramer, Jayashree; Polaskova, Pavlina; Gerstner, Elizabeth R.] Harvard Univ, Sch Med, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Massachus, Boston, MA 02115 USA. [Batchelor, Tracy T.; Gerstner, Elizabeth R.; Dietrich, Jorg] Harvard Univ, Sch Med, Dept Neurol, Ctr Neurooncol,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Dietrich, J (reprint author), Harvard Univ, Sch Med, Boston, MA 02138 USA. EM dietrich.jorg@mgh.harvard.edu OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 FU National Cancer Institute; NIH [R01CA129371, K24CA125440A]; American Academy of Neurology Clinical Research Training Fellowship; K-12 institutional award; American Cancer Society; Department of Radiology at the Massachusetts General Hospital FX This work was conducted with support from the National Cancer Institute and NIH, R01CA129371 and K24CA125440A (T.T.B.). J.D. is a recipient of the American Academy of Neurology Clinical Research Training Fellowship. This work has also been supported by a K-12 institutional award (to J.D.), the American Cancer Society (to J.D.), internal funds from the Department of Radiology at the Massachusetts General Hospital (to E.G., K.J., J.K., and P.P.), and philanthropic support (to J.D.). NR 36 TC 10 Z9 10 U1 1 U2 3 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 AUG 25 PY 2015 VL 85 IS 8 BP 683 EP 691 DI 10.1212/WNL.0000000000001861 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CQ1ML UT WOS:000360361700006 PM 26208964 ER PT J AU Nabet, B Broin, PO Reyes, JM Shieh, K Lin, CY Will, CM Popovic, R Ezponda, T Bradner, JE Golden, AA Licht, JD AF Nabet, Behnam Broin, Pilib O. Reyes, Jaime M. Shieh, Kevin Lin, Charles Y. Will, Christine M. Popovic, Relja Ezponda, Teresa Bradner, James E. Golden, Aaron A. Licht, Jonathan D. TI Deregulation of the Ras-Erk Signaling Axis Modulates the Enhancer Landscape SO CELL REPORTS LA English DT Article ID DEMETHYLASE JMJD3 CONTRIBUTES; PROTEIN-KINASE-C; TRANSCRIPTION FACTORS; SELECTIVE-INHIBITION; SUPER-ENHANCERS; GENE-EXPRESSION; HISTONE H3; CANCER; PHOSPHORYLATION; CHROMATIN AB Unrestrained receptor tyrosine kinase (RTK) signaling and epigenetic deregulation are root causes of tumorigenesis. We establish linkage between these processes by demonstrating that aberrant RTK signaling unleashed by oncogenic HRas(G12V) or loss of negative feedback through Sprouty gene deletion remodels histone modifications associated with active typical and super-enhancers. However, although both lesions disrupt the Ras-Erk axis, the expression programs, enhancer signatures, and transcription factor networks modulated upon HRas(G12V) transformation or Sprouty deletion are largely distinct. Oncogenic HRas(G12V) elevates histone 3 lysine 27 acetylation (H3K27ac) levels at enhancers near the transcription factor Gata4 and the kinase Prkcb, as well as their expression levels. We show that Gata4 is necessary for the aberrant gene expression and H3K27ac marking at enhancers, and Prkcb is required for the oncogenic effects of HRas(G12V)-driven cells. Taken together, our findings demonstrate that dynamic reprogramming of the cellular enhancer landscape is a major effect of oncogenic RTK signaling. C1 [Nabet, Behnam; Will, Christine M.; Popovic, Relja; Ezponda, Teresa; Licht, Jonathan D.] Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA. [Nabet, Behnam] Northwestern Univ, Driskill Grad Program Life Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Broin, Pilib O.; Shieh, Kevin; Golden, Aaron A.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. [Reyes, Jaime M.; Lin, Charles Y.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Golden, Aaron A.] Yeshiva Univ, Dept Math Sci, New York, NY 10033 USA. RP Licht, JD (reprint author), Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA. EM j-licht@northwestern.edu FU NIH [CA59998, GM08061]; Lynn Sage Foundation; Northwestern Memorial Foundation; NCI Physical Sciences-Oncology Center [U54CA143869]; Northwestern University Malkin Scholars Award; NIGMS [GM007288]; Department of Defense CDMRP [CA120184] FX This work was initiated under grants from the NIH (CA59998) and the Lynn Sage and Northwestern Memorial Foundations and supported by a NCI Physical Sciences-Oncology Center grant (U54CA143869 to J.D.L.). This work was also supported by an NIH T32 training grant (GM08061 to B.N.), a Northwestern University Malkin Scholars Award (B.N.), an NIGMS T32 training grant (GM007288 to K.S.), and a Department of Defense CDMRP (CA120184 to C.Y.L.). We thank members of the J.D.L. laboratory and Suzanne Nabet for helpful discussions and critical review of the manuscript. NR 45 TC 3 Z9 3 U1 0 U2 7 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 AUG 25 PY 2015 VL 12 IS 8 BP 1300 EP 1313 DI 10.1016/j.celrep.2015.06.078 PG 14 WC Cell Biology SC Cell Biology GA CP8YZ UT WOS:000360182200009 PM 26279576 ER PT J AU Klco, JM Miller, CA Griffith, M Petti, A Spencer, DH Ketkar-Kulkarni, S Wartman, LD Christopher, M Lamprecht, TL Helton, NM Duncavage, EJ Payton, JE Baty, J Heath, SE Griffith, OL Shen, D Hundal, J Chang, GS Fulton, R O'Laughlin, M Fronick, C Magrini, V Demeter, RT Larson, DE Kulkarni, S Ozenberger, BA Welch, JS Walter, MJ Graubert, TA Westervelt, P Radich, JP Link, DC Mardis, ER DiPersio, JF Wilson, RK Ley, TJ AF Klco, Jeffery M. Miller, Christopher A. Griffith, Malachi Petti, Allegra Spencer, David H. Ketkar-Kulkarni, Shamika Wartman, Lukas D. Christopher, Matthew Lamprecht, Tamara L. Helton, Nicole M. Duncavage, Eric J. Payton, Jacqueline E. Baty, Jack Heath, Sharon E. Griffith, Obi L. Shen, Dong Hundal, Jasreet Chang, Gue Su Fulton, Robert O'Laughlin, Michelle Fronick, Catrina Magrini, Vincent Demeter, Ryan T. Larson, David E. Kulkarni, Shashikant Ozenberger, Bradley A. Welch, John S. Walter, Matthew J. Graubert, Timothy A. Westervelt, Peter Radich, Jerald P. Link, Daniel C. Mardis, Elaine R. DiPersio, John F. Wilson, Richard K. Ley, Timothy J. TI Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MINIMAL RESIDUAL DISEASE; COOPERATIVE-ONCOLOGY-GROUP; COMPLETE REMISSION; ADULT PATIENTS; CLONAL HEMATOPOIESIS; CYTOGENETIC ABNORMALITIES; PROGNOSTIC IMPACT; STEM-CELLS; RELAPSE; CANCER AB IMPORTANCE Tests that predict outcomes for patients with acute myeloid leukemia (AML) are imprecise, especially for those with intermediate risk AML. OBJECTIVES To determine whether genomic approaches can provide novel prognostic information for adult patients with de novo AML. DESIGN, SETTING, AND PARTICIPANTS Whole-genome or exome sequencing was performed on samples obtained at disease presentation from 71 patients with AML (mean age, 50.8 years) treated with standard induction chemotherapy at a single site starting in March 2002, with follow-up through January 2015. In addition, deep digital sequencing was performed on paired diagnosis and remission samples from 50 patients (including 32 with intermediate-risk AML), approximately 30 days after successful induction therapy. Twenty-five of the 50 were from the cohort of 71 patients, and 25 were new, additional cases. EXPOSURES Whole-genome or exome sequencing and targeted deep sequencing. Risk of identification based on genetic data. MAIN OUTCOMES AND MEASURES Mutation patterns (including clearance of leukemia-associated variants after chemotherapy) and their association with event-free survival and overall survival. RESULTS Analysis of comprehensive genomic data from the 71 patients did not improve outcome assessment over current standard-of-care metrics. In an analysis of 50 patients with both presentation and documented remission samples, 24 (48%) had persistent leukemia-associated mutations in at least 5% of bone marrow cells at remission. The 24 with persistent mutations had significantly reduced event-free and overall survival vs the 26 who cleared all mutations. Patients with intermediate cytogenetic risk profiles had similar findings. [GRAPHICS] CONCLUSIONS AND RELEVANCE The detection of persistent leukemia-associated mutations in at least 5% of bone marrow cells in day 30 remission samples was associated with a significantly increased risk of relapse, and reduced overall survival. These data suggest that this genomic approach may improve risk stratification for patients with AML. C1 [Klco, Jeffery M.; Spencer, David H.; Duncavage, Eric J.; Payton, Jacqueline E.; Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Klco, Jeffery M.; Lamprecht, Tamara L.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Miller, Christopher A.; Griffith, Malachi; Petti, Allegra; Ketkar-Kulkarni, Shamika; Griffith, Obi L.; Shen, Dong; Hundal, Jasreet; Chang, Gue Su; Fulton, Robert; O'Laughlin, Michelle; Fronick, Catrina; Magrini, Vincent; Demeter, Ryan T.; Larson, David E.; Ozenberger, Bradley A.; Mardis, Elaine R.; Wilson, Richard K.; Ley, Timothy J.] Washington Univ, McDonnell Genome Inst, St Louis, MO USA. [Miller, Christopher A.; Petti, Allegra; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Dept Med, Div Genom & Bioinformat, St Louis, MO USA. [Griffith, Malachi; Wartman, Lukas D.; Fulton, Robert; Magrini, Vincent; Larson, David E.; Kulkarni, Shashikant; Mardis, Elaine R.; Wilson, Richard K.; Ley, Timothy J.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Ketkar-Kulkarni, Shamika; Christopher, Matthew; Lamprecht, Tamara L.; Helton, Nicole M.; Heath, Sharon E.; Griffith, Obi L.; Ozenberger, Bradley A.; Welch, John S.; Walter, Matthew J.; Graubert, Timothy A.; Westervelt, Peter; Link, Daniel C.; DiPersio, John F.; Ley, Timothy J.] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. [Baty, Jack] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Shen, Dong] Medimmune AstraZeneca, Gaithersburg, MD USA. [Kulkarni, Shashikant] Washington Univ, Dept Pediat, Div Hematol Oncol, St Louis, MO 63130 USA. [Graubert, Timothy A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Radich, Jerald P.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Ley, TJ (reprint author), Washington Univ, Sch Med, 660 South Euclid Ave,Campus Box 8007, St Louis, MO 63110 USA. EM timley@wustl.edu OI Griffith, Obi/0000-0002-0843-4271; Griffith, Malachi/0000-0002-6388-446X; Klco, Jeffery/0000-0003-2961-6960 FU National Institutes of Health [KO8 HL116605, PO1 CA101937, U54 HG003079]; Barnes-Jewish Hospital Foundation [00335-0505-02]; National Cancer Institute Cancer Center [P30CA91842]; Burroughs Wellcome Fund FX This work was supported by grants KO8 HL116605 (Dr Klco), PO1 CA101937 (Dr Ley), and U54 HG003079 (Dr Wilson) from the National Institutes of Health and grant 00335-0505-02 (Dr Ley) from the Barnes-Jewish Hospital Foundation. Technical assistance was provided by the Alvin J. Siteman Cancer Center Tissue Procurement Core, the High Speed Cell Sorting Core, and the Molecular and Genomic Analysis Core at Washington University School of Medicine and Barnes-Jewish Hospital in St Louis, Missouri, which are all supported by grant P30CA91842 from the National Cancer Institute Cancer Center. Dr Klco reports holding a Career Award for Medical Scientists from the Burroughs Wellcome Fund. NR 34 TC 57 Z9 59 U1 1 U2 8 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 AUG 25 PY 2015 VL 314 IS 8 BP 811 EP 822 DI 10.1001/jama.2015.9643 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CP6SA UT WOS:000360017200021 PM 26305651 ER PT J AU McNamara, DM Elkayam, U Alharethi, R Damp, J Hsich, E Ewald, G Modi, K Alexis, JD Ramani, GV Semigran, MJ Haythe, J Markham, DW Marek, J Gorcsan, J Wu, WC Lin, Y Halder, I Pisarcik, J Cooper, LT Fett, JD AF McNamara, Dennis M. Elkayam, Uri Alharethi, Rami Damp, Julie Hsich, Eileen Ewald, Gregory Modi, Kalgi Alexis, Jeffrey D. Ramani, Gautam V. Semigran, Marc J. Haythe, Jennifer Markham, David W. Marek, Josef Gorcsan, John, III Wu, Wen-Chi Lin, Yan Halder, Indrani Pisarcik, Jessica Cooper, Leslie T. Fett, James D. CA IPAC Investigators TI Clinical Outcomes for Peripartum Cardiomyopathy in North America Results of the IPAC Study (Investigations of Pregnancy-Associated Cardiomyopathy) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE heart failure; myocardial recovery; race; remodeling ID DILATED CARDIOMYOPATHY; HEART-FAILURE; TASK-FORCE; PREDICTORS; MYOCARDITIS; GUIDELINES; MANAGEMENT; MUTATIONS; MORTALITY; RECOVERY AB BACKGROUND Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. OBJECTIVES This study sought to prospectively evaluate recovery of the left ventricular ejection fraction (LVEF) and clinical outcomes in the multicenter IPAC (Investigations of Pregnancy Associated Cardiomyopathy) study. METHODS We enrolled and followed 100 women with PPCM through 1 year post-partum. The LVEF was assessed by echocardiography at baseline and at 2, 6, and 12 months post-partum. Survival free from major cardiovascular events (death, transplantation, or left ventricular [LV] assist device) was determined. Predictors of outcome, particularly race, parameters of LV dysfunction (LVEF), and remodeling (left ventricular end-diastolic diameter [LVEDD]) at presentation, were assessed by univariate and multivariate analyses. RESULTS The cohort was 30% black, 65% white, 5% other; the mean patient age was 30 +/- 6 years; and 88% were receiving beta-blockers and 81% angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The LVEF at study entry was 0.35 +/- 0.10, 0.51 +/- 0.11 at 6 months, and 0.53 +/- 0.10 at 12 months. By 1 year, 13% had experienced major events or had persistent severe cardiomyopathy with an LVEF < 0.35, and 72% achieved an LVEF >= 0.50. An initial LVEF < 0.30 (p = 0.001), an LVEDD >= 6.0cm (p < 0.001), black race (p = 0.001), and presentation after 6 weeks postpartum (p = 0.02) were associated with a lower LVEF at 12 months. No subjects with both a baseline LVEF < 0.30 and an LVEDD >= 6.0 cm recovered by 1 year post-partum, whereas 91% with both a baseline LVEF >= 0.30 and an LVEDD < 6.0 cm recovered (p < 0.00001). CONCLUSIONS In a prospective cohort with PPCM, most women recovered; however, 13% had major events or persistent severe cardiomyopathy. Black women had more LV dysfunction at presentation and at 6 and 12 months post-partum. Severe LV dysfunction and greater remodeling at study entry were associated with less recovery. (Investigations of Pregnancy Associated Cardiomyopathy [IPAC]; NCT01085955) (C) 2015 by the American College of Cardiology Foundation. C1 [McNamara, Dennis M.; Marek, Josef; Gorcsan, John, III; Pisarcik, Jessica; Fett, James D.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Elkayam, Uri] Univ So Calif, Los Angeles, CA USA. [Alharethi, Rami] Intermt Med Ctr, Salt Lake City, UT USA. [Damp, Julie] Vanderbilt Univ, Nashville, TN 37235 USA. [Hsich, Eileen] Cleveland Clin, Cleveland, OH 44106 USA. [Ewald, Gregory] Washington Univ, St Louis, MO USA. [Modi, Kalgi] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA. [Alexis, Jeffrey D.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Ramani, Gautam V.] Univ Maryland, Baltimore, MD 21201 USA. [Semigran, Marc J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Haythe, Jennifer] Columbia Univ, New York, NY USA. [Markham, David W.] Emory Univ, Atlanta, GA 30322 USA. [Wu, Wen-Chi; Lin, Yan] Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Halder, Indrani] Univ Pittsburgh, Heart Lung Blood & Vasc Med Inst, Pittsburgh, PA 15213 USA. [Cooper, Leslie T.] Mayo Clin, Rochester, MN USA. RP McNamara, DM (reprint author), Univ Pittsburgh, Inst Heart & Vasc, Med Ctr, 566 Scaife Hall,200 Lothrop St, Pittsburgh, PA 15213 USA. EM mcnamaradm@upmc.edu FU NHLBI NIH HHS [HL102429] NR 25 TC 28 Z9 31 U1 2 U2 9 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 AUG 25 PY 2015 VL 66 IS 8 BP 905 EP 914 DI 10.1016/j.jacc.2015.06.1309 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP5VQ UT WOS:000359953500005 PM 26293760 ER PT J AU Costales, JA Kotton, CN Zurita-Leal, AC Garcia-Perez, J Llewellyn, MS Messenger, LA Bhattacharyya, T Burleigh, BA AF Costales, Jaime A. Kotton, Camille N. Zurita-Leal, Andrea C. Garcia-Perez, Josselyn Llewellyn, Martin S. Messenger, Louisa A. Bhattacharyya, Tapan Burleigh, Barbara A. TI Chagas disease reactivation in a heart transplant patient infected by domestic Trypanosoma cruzi discrete typing unit l (Tcl(DOM)) SO PARASITES & VECTORS LA English DT Article DE Trypanosoma cruzi; Lineage; Reactivation; Chagasic cardiomyopathy; Chagas disease ID EPIDEMIOLOGY; DIVERSITY; LINEAGE AB Background: Trypanosoma cruzi, causative agent of Chagas disease, displays high intraspecific genetic diversity: six genetic lineages or discrete typing units (DTUs) are currently recognized, termed TcI through TcVI. Each DTU presents a particular distribution pattern across the Americas, and is loosely associated with different transmission cycles and hosts. Several DTUs are known to circulate in Central America. It has been previously suggested that TcI infection is benign and does not lead to chronic chagasic cardiomyopathy (CCC). Findings: In this study, we genotyped T. cruzi parasites circulating in the blood and from explanted cardiac tissue of an El Salvadorian patient who developed reactivation Chagas disease while on immunosuppressive medications after undergoing heart transplant in the U.S. as treatment for end-stage CCC. Parasite typing was performed through molecular methods (restriction fragment length polymorphism of polymerase reaction chain amplified products, microsatellite typing, maxicircle sequence typing and low-stringency single primer PCR, [LSSP-PCR]) as well as lineage-specific serology. We show that the parasites infecting the patient belong to the TcI DTU exclusively. Our data indicate that the parasites isolated from the patient belong to a genotype frequently associated with human infection throughout the Americas (TcIDOM). Conclusions: Our results constitute compelling evidence in support of TcI DTU's ability to cause end-stage CCC and help dispel any residual bias that infection with this lineage is benign, pointing to the need for increased surveillance for dissemination of this genotype in endemic regions, the USA and globally. C1 [Costales, Jaime A.; Zurita-Leal, Andrea C.; Garcia-Perez, Josselyn] Pontificia Univ Catolica Ecuador, Escuela Biol, Ctr Invest Enfermedades Infecciosas, Quito, Ecuador. [Kotton, Camille N.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Llewellyn, Martin S.; Messenger, Louisa A.; Bhattacharyya, Tapan] London Sch Hyg & Trop Med, Dept Pathogen Mol Biol, London WC1, England. [Burleigh, Barbara A.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Costales, JA (reprint author), Pontificia Univ Catolica Ecuador, Escuela Biol, Ctr Invest Enfermedades Infecciosas, Ave 12 Octubre & Roca, Quito, Ecuador. EM jacostalesc@puce.edu.ec FU PUCE FX We thank Fernanda Latorre, Alejandra Zurita for technical assistance, Gert Van der Auwera for valuable discussion of the data, Mario Grijalva and Michael Miles for critical reading of the manuscript. Work was funded by PUCE. NR 18 TC 4 Z9 4 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-3305 J9 PARASITE VECTOR JI Parasites Vectors PD AUG 25 PY 2015 VL 8 AR 435 DI 10.1186/s13071-015-1039-3 PG 6 WC Parasitology SC Parasitology GA CP6GP UT WOS:000359984000001 PM 26303927 ER PT J AU Bernstein, AM Song, MY Zhang, XH Pan, A Wang, ML Fuchs, CS Le, N Chan, AT Willett, WC Ogino, S Giovannucci, EL Wu, KN AF Bernstein, Adam M. Song, Mingyang Zhang, Xuehong Pan, An Wang, Molin Fuchs, Charles S. Le, Ngoan Chan, Andrew T. Willett, Walter C. Ogino, Shuji Giovannucci, Edward L. Wu, Kana TI Processed and Unprocessed Red Meat and Risk of Colorectal Cancer: Analysis by Tumor Location and Modification by Time SO PLOS ONE LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; LIFE-STYLE; COLON-CANCER; EPIDEMIOLOGIC EVIDENCE; PROXIMAL COLON; RECTAL-CANCER; EPIC-NORFOLK; DISTAL COLON; CONSUMPTION; COHORT AB Although the association between red meat consumption and colorectal cancer (CRC) is well established, the association across subsites of the colon and rectum remains uncertain, as does time of consumption in relation to cancer development. As these relationships are key for understanding the pathogenesis of CRC, they were examined in two large cohorts with repeated dietary measures over time, the Nurses' Health Study (n = 87,108 women, 1980-2010) and Health Professionals Follow-up Study (n = 47,389 men, 1986-2010). Cox proportional hazards regression models generated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled by random-effects meta-analysis. In combined cohorts, there were 2,731 CRC cases (1,151 proximal colon, 816 distal colon, and 589 rectum). In pooled analyses, processed red meat was positively associated with CRC risk (per 1 serving/day increase: HR = 1.15, 95% CI: 1.01-1.32; P for trend 0.03) and particularly with distal colon cancer (per 1 serving/day increase; HR = 1.36; 95% CI: 1.09-1.69; P for trend 0.006). Recent consumption of processed meat (within the past 4 years) was not associated with distal cancer. Unprocessed red meat was inversely associated with risk of distal colon cancer and a weak non-significant positive association between unprocessed red meat and proximal cancer was observed (per 1 serving/day increase: distal HR = 0.75; 95% CI: 0.68-0.82; P for trend <0.001; proximal HR = 1.14, 95% CI: 0.92-1.40; P for trend 0.22). Thus, in these two large cohorts of US health professionals, processed meat intake was positively associated with risk of CRC, particularly distal cancer, with little evidence that higher intake of unprocessed red meat substantially increased risk of CRC. Future studies, particularly those with sufficient sample size to assess associations by subsites across the colon are needed to confirm these findings and elucidate potentially distinct mechanisms underlying the relationship between processed meat and subtypes of unprocessed red meat with CRC. C1 [Bernstein, Adam M.] Rally Hlth, San Francisco, CA USA. [Song, Mingyang; Zhang, Xuehong; Le, Ngoan; Willett, Walter C.; Giovannucci, Edward L.; Wu, Kana] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Song, Mingyang; Willett, Walter C.; Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Pan, An] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Epidemiol & Biostat, Wuhan, Hubei, Peoples R China. [Wang, Molin] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Chan, Andrew T.; Willett, Walter C.; Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Le, Ngoan] Hanoi Med Univ, Hanoi, Vietnam. [Chan, Andrew T.; Willett, Walter C.; Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Wu, KN (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM kana.wu@channing.harvard.edu RI Song, Mingyang/M-6701-2013; Pan, An/C-5572-2011 OI Song, Mingyang/0000-0002-1324-0316; Pan, An/0000-0002-1089-7945 FU Entertainment Industry Foundation's National Colorectal Cancer Research Alliance (NCCRA); UICC American Cancer Society Beginning Investigator Fellowship - American Cancer Society; [UM1 CA167552]; [P01 CA 55075]; [P01 CA055075]; [UM1 CA186107]; [P01 CA87969] FX This research was funded by the following federal grants: P01 CA87969, UM1 CA167552, P01 CA 55075, P01 CA055075, UM1 CA167552, UM1 CA186107, and P01 CA87969. In addition, funding came from the Entertainment Industry Foundation's National Colorectal Cancer Research Alliance (NCCRA). This work was also supported by a UICC American Cancer Society Beginning Investigator Fellowship (Dr. Ngoan Le), funded by the American Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 12 Z9 12 U1 3 U2 43 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 AUG 25 PY 2015 VL 10 IS 8 AR e0135959 DI 10.1371/journal.pone.0135959 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP6KK UT WOS:000359995500039 PM 26305323 ER PT J AU Gornalusse, GG Mummidi, S Gaitan, AA Jimenez, F Ramsuran, V Picton, A Rogers, K Manoharan, MS Avadhanam, N Murthy, KK Martinez, H Murillo, AM Chykarenko, ZA Hutt, R Daskalakis, D Shostakovich-Koretskaya, L Karim, SA Martin, JN Deeks, SG Hecht, F Sinclair, E Clark, RA Okulicz, J Valentine, FT Martinson, N Tiemessen, CT Ndung'u, T Hunt, PW He, WJ Ahuja, SK AF Gornalusse, German G. Mummidi, Srinivas Gaitan, Alvaro A. Jimenez, Fabio Ramsuran, Veron Picton, Anabela Rogers, Kristen Manoharan, Muthu Saravanan Avadhanam, Nymisha Murthy, Krishna K. Martinez, Hernan Murillo, Angela Molano Chykarenko, Zoya A. Hutt, Richard Daskalakis, Demetre Shostakovich-Koretskaya, Ludmila Karim, Salim Abdool Martin, Jeffrey N. Deeks, Steven G. Hecht, Frederick Sinclair, Elizabeth Clark, Robert A. Okulicz, Jason Valentine, Fred T. Martinson, Neil Tiemessen, Caroline Tanya Ndung'u, Thumbi Hunt, Peter W. He, Weijing Ahuja, Sunil K. TI Epigenetic mechanisms, T-cell activation, and CCR5 genetics interact to regulate T-cell expression of CCR5, the major HIV-1 coreceptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV; CCR5; methylation; T-cell activation; polymorphism ID IMMUNODEFICIENCY-VIRUS TYPE-1; TRANSCRIPTION FACTOR; DNA METHYLATION; UNINFECTED INDIVIDUALS; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; MESSENGER-RNA; IN-VITRO; INFECTION; PROMOTER AB T-cell expression levels of CC chemokine receptor 5 (CCR5) are a critical determinant of HIV/AIDS susceptibility, and manifest wide variations (i) between T-cell subsets and among individuals and (ii) in T-cell activation-induced increases in expression levels. We demonstrate that a unifying mechanism for this variation is differences in constitutive and T-cell activation-induced DNA methylation status of CCR5 cis-regulatory regions (cis-regions). Commencing at an evolutionarily conserved CpG (CpG-41), CCR5 cis-regions manifest lower vs. higher methylation in T cells with higher vs. lower CCR5 levels (memory vs. naive T cells) and in memory T cells with higher vs. lower CCR5 levels. HIV-related and in vitro induced T-cell activation is associated with demethylation of these cis-regions. CCR5 haplotypes associated with increased vs. decreased gene/surface expression levels and HIV/AIDS susceptibility magnify vs. dampen T-cell activation-associated demethylation. Methylation status of CCR5 intron 2 explains a larger proportion of the variation in CCR5 levels than genotype or T-cell activation. The ancestral, protective CCR5-HHA haplotype bears a polymorphism at CpG-41 that is (i) specific to southern Africa, (ii) abrogates binding of the transcription factor CREB1 to this cis-region, and (iii) exhibits a trend for overrepresentation in persons with reduced susceptibility to HIV and disease progression. Genotypes lacking the CCR5-Delta 32 mutation but with hypermethylated cis-regions have CCR5 levels similar to genotypes heterozygous for CCR5-.32. In HIV-infected individuals, CCR5 cis-regions remain demethylated, despite restoration of CD4+ counts (>= 800 cells per mm(3)) with antiretroviral therapy. Thus, methylation content of CCR5 cis-regions is a central epigenetic determinant of T-cell CCR5 levels, and possibly HIV-related outcomes. C1 [Gornalusse, German G.; Mummidi, Srinivas; Gaitan, Alvaro A.; Jimenez, Fabio; Rogers, Kristen; Manoharan, Muthu Saravanan; Avadhanam, Nymisha; Martinez, Hernan; Murillo, Angela Molano; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX 78229 USA. [Gornalusse, German G.; Mummidi, Srinivas; Gaitan, Alvaro A.; Jimenez, Fabio; Rogers, Kristen; Manoharan, Muthu Saravanan; Avadhanam, Nymisha; Martinez, Hernan; Murillo, Angela Molano; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX 78229 USA. [Gornalusse, German G.; Mummidi, Srinivas; Gaitan, Alvaro A.; Jimenez, Fabio; Rogers, Kristen; Manoharan, Muthu Saravanan; Avadhanam, Nymisha; Martinez, Hernan; Murillo, Angela Molano; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Gornalusse, German G.; Rogers, Kristen; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol, San Antonio, TX 78229 USA. [Ramsuran, Veron; Ndung'u, Thumbi] Univ KwaZulu Natal, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa. [Ramsuran, Veron; Karim, Salim Abdool; Ndung'u, Thumbi] Univ KwaZulu Natal, Ctr AIDS Program Res South Africa CAPRISA, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, ZA-4013 Durban, South Africa. [Picton, Anabela; Tiemessen, Caroline Tanya] Natl Inst Communicable Dis, Ctr HIV & Sexually Transmitted Infect, ZA-2131 Johannesburg, South Africa. [Picton, Anabela; Martinson, Neil; Tiemessen, Caroline Tanya] Univ Witwatersrand, Fac Hlth Sci, ZA-2193 Johannesburg, South Africa. [Murthy, Krishna K.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX 78245 USA. [Chykarenko, Zoya A.; Shostakovich-Koretskaya, Ludmila] Dnepropetrovsk State Med Acad, Dept Gen Pediat & Pediat Infect Dis, UA-49044 Dnepropetrovsk, Ukraine. [Hutt, Richard; Daskalakis, Demetre; Valentine, Fred T.] NYU, Sch Med, Dept Med, New York, NY 10016 USA. [Martin, Jeffrey N.; Deeks, Steven G.; Hecht, Frederick; Sinclair, Elizabeth; Hunt, Peter W.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94110 USA. [Martin, Jeffrey N.; Deeks, Steven G.; Hecht, Frederick; Sinclair, Elizabeth; Hunt, Peter W.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94110 USA. [Martin, Jeffrey N.; Deeks, Steven G.; Hecht, Frederick; Sinclair, Elizabeth; Hunt, Peter W.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Okulicz, Jason] San Antonio Mil Med Ctr, San Antonio, TX 78234 USA. [Martinson, Neil] Univ Witwatersrand, Perinatal HIV Res Unit, ZA-2193 Johannesburg, South Africa. [Martinson, Neil; Tiemessen, Caroline Tanya] MRC, Soweto Matlosana Ctr HIV AIDS & TB, ZA-2193 Johannesburg, South Africa. [Martinson, Neil] Johns Hopkins Univ, Sch Med, Ctr TB Res, Baltimore, MD 21205 USA. RP Ahuja, SK (reprint author), South Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX 78229 USA. EM ahujas@uthscsa.edu OI Ndung'u, Thumbi/0000-0003-2962-3992; Valentine, Fred/0000-0002-6046-5913; Abdool Karim, Salim/0000-0002-4986-2133 FU BLRD VA [I01 BX000975]; CSRD VA [IP1 CX000875]; NCATS NIH HHS [UL1 TR001120]; NCI NIH HHS [NIH-NCI P30CA54174]; NCRR NIH HHS [UL1 RR024131, UL1RR025767]; NHLBI NIH HHS [R01HL090312]; NIAID NIH HHS [NIH P01AI057127, P30 AI027763, P30AI027742, R01 AI043279, R01-AI043279, R24 AI067039, R37-AI046326, U19 AI 51794]; NIH HHS [P51 OD011133]; NIMH NIH HHS [P30 MH62246] NR 44 TC 7 Z9 7 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2015 VL 112 IS 34 BP E4762 EP E4771 DI 10.1073/pnas.1423228112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP6NZ UT WOS:000360005600018 PM 26307764 ER PT J AU Steinbaugh, MJ Narasimhan, SD Robida-Stubbs, S Mazzeo, LEM Dreyfuss, JM Hourihan, JM Raghavan, P Operana, TN Esmaillie, R Blackwell, TK AF Steinbaugh, Michael J. Narasimhan, Sri Devi Robida-Stubbs, Stacey Mazzeo, Lorenza E. Moronetti Dreyfuss, Jonathan M. Hourihan, John M. Raghavan, Prashant Operana, Theresa N. Esmaillie, Reza Blackwell, T. Keith TI Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence SO ELIFE LA English DT Article ID OXIDATIVE STRESS-RESPONSE; LIFE-SPAN EXTENSION; CAENORHABDITIS-ELEGANS; C-ELEGANS; REPRODUCTIVE-SYSTEM; EXPRESSION ANALYSIS; PROLINE CATABOLISM; MICROARRAY DATA; GENE-REGULATION; FAT-METABOLISM AB In Caenorhabditis elegans, ablation of germline stem cells (GSCs) extends lifespan, but also increases fat accumulation and alters lipid metabolism, raising the intriguing question of how these effects might be related. Here, we show that a lack of GSCs results in a broad transcriptional reprogramming in which the conserved detoxification regulator SKN-1/Nrf increases stress resistance, proteasome activity, and longevity. SKN-1 also activates diverse lipid metabolism genes and reduces fat storage, thereby alleviating the increased fat accumulation caused by GSC absence. Surprisingly, SKN-1 is activated by signals from this fat, which appears to derive from unconsumed yolk that was produced for reproduction. We conclude that SKN-1 plays a direct role in maintaining lipid homeostasis in which it is activated by lipids. This SKN-1 function may explain the importance of mammalian Nrf proteins in fatty liver disease and suggest that particular endogenous or dietary lipids might promote health through SKN-1/Nrf. C1 [Steinbaugh, Michael J.; Narasimhan, Sri Devi; Robida-Stubbs, Stacey; Mazzeo, Lorenza E. Moronetti; Dreyfuss, Jonathan M.; Raghavan, Prashant; Operana, Theresa N.; Esmaillie, Reza; Blackwell, T. Keith] Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. [Steinbaugh, Michael J.; Narasimhan, Sri Devi; Robida-Stubbs, Stacey; Mazzeo, Lorenza E. Moronetti; Hourihan, John M.; Raghavan, Prashant; Operana, Theresa N.; Esmaillie, Reza; Blackwell, T. Keith] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Steinbaugh, Michael J.; Narasimhan, Sri Devi; Robida-Stubbs, Stacey; Mazzeo, Lorenza E. Moronetti; Hourihan, John M.; Raghavan, Prashant; Operana, Theresa N.; Esmaillie, Reza; Blackwell, T. Keith] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA USA. [Dreyfuss, Jonathan M.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Blackwell, TK (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu OI Steinbaugh, Michael/0000-0002-2403-2221 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) NRSA Institutional Postdoctoral Training Grant [T32DK007260]; National Institute of General Medical Sciences (NIGMS) [R01GM062891, R01GM094398]; National Institute on Aging [R21AG043949]; Myra Reinhard Family Foundation; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetes Research Center Award [P30DK036836]; National Institutes of Health (NIH) Office of Research Infrastructure Programs [P40 OD010440] FX National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) NRSA Institutional Postdoctoral Training Grant, T32DK007260 Michael J Steinbaugh; National Institute of General Medical Sciences (NIGMS) R01GM062891 T Keith Blackwell; National Institute of General Medical Sciences (NIGMS) R01GM094398 T Keith Blackwell; National Institute on Aging R21AG043949 T Keith Blackwell; Myra Reinhard Family Foundation Research Award T Keith Blackwell; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetes Research Center Award, P30DK036836 T Keith Blackwell; National Institutes of Health (NIH) Office of Research Infrastructure Programs (P40 OD010440) T Keith Blackwell; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. NR 119 TC 16 Z9 16 U1 0 U2 0 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD AUG 24 PY 2015 VL 4 AR e07836 DI 10.7554/eLife.07836 PG 28 WC Biology SC Life Sciences & Biomedicine - Other Topics GA DI9IQ UT WOS:000373816500001 ER PT J AU Mahmoud, AI O'Meara, CC Gemberling, M Zhao, L Bryant, DM Zheng, RM Gannon, JB Cai, L Choi, WY Egnaczyk, GF Burns, CE Burns, CG MacRae, CA Poss, KD Lee, RT AF Mahmoud, Ahmed I. O'Meara, Caitlin C. Gemberling, Matthew Zhao, Long Bryant, Donald M. Zheng, Ruimao Gannon, Joseph B. Cai, Lei Choi, Wen-Yee Egnaczyk, Gregory F. Burns, Caroline E. Burns, C. Geoffrey MacRae, Calum A. Poss, Kenneth D. Lee, Richard T. TI Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration SO DEVELOPMENTAL CELL LA English DT Article ID NEONATAL MOUSE HEART; CELL-CYCLE ARREST; CARDIAC REGENERATION; SYMPATHETIC INNERVATION; CHOLINERGIC REGULATION; LIMB REGENERATION; MIR-15 FAMILY; ADULT HEART; ZEBRAFISH; GROWTH AB Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration. C1 [Mahmoud, Ahmed I.; O'Meara, Caitlin C.; Bryant, Donald M.; Zheng, Ruimao; Gannon, Joseph B.; Cai, Lei; Lee, Richard T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02139 USA. [Mahmoud, Ahmed I.; O'Meara, Caitlin C.; Bryant, Donald M.; Zheng, Ruimao; Gannon, Joseph B.; Cai, Lei; Lee, Richard T.] Brigham & Womens Hosp, Brigham Regenerat Med Ctr, Cambridge, MA 02139 USA. [Mahmoud, Ahmed I.; O'Meara, Caitlin C.; Bryant, Donald M.; Zheng, Ruimao; Gannon, Joseph B.; Lee, Richard T.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Mahmoud, Ahmed I.; O'Meara, Caitlin C.; Zhao, Long; Bryant, Donald M.; Zheng, Ruimao; Gannon, Joseph B.; Cai, Lei; Burns, Caroline E.; Burns, C. Geoffrey; MacRae, Calum A.; Lee, Richard T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Zhao, Long; Burns, C. Geoffrey; MacRae, Calum A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Charlestown, MA 02129 USA. [Zhao, Long; Burns, Caroline E.; Burns, C. Geoffrey] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Mahmoud, Ahmed I.; O'Meara, Caitlin C.; Bryant, Donald M.; Zheng, Ruimao; Gannon, Joseph B.; Cai, Lei; MacRae, Calum A.; Lee, Richard T.] Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. [Mahmoud, Ahmed I.; O'Meara, Caitlin C.; Bryant, Donald M.; Zheng, Ruimao; Gannon, Joseph B.; Cai, Lei; MacRae, Calum A.; Lee, Richard T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gemberling, Matthew; Choi, Wen-Yee; Egnaczyk, Gregory F.; Poss, Kenneth D.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. [Gemberling, Matthew; Choi, Wen-Yee; Egnaczyk, Gregory F.; Poss, Kenneth D.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. RP Lee, RT (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02139 USA. EM rlee@partners.org RI Zhao, Long/A-6439-2014 FU American Heart Association Postdoctoral fellowship [15POST21870000]; NIH [F32HL117595, F32 HL106987-02, HL127067, HL081674, AG040019, HL117986]; HHMI Gilliam Fellowship; American Heart Association (AHA) [14POST20380738] FX We thank the R.T.L. and K.D.P. laboratory members for helpful discussions, J. Burris, N. Blake, S. Davies, and A. Dunlap for zebrafish care, and A. Dickson for quantitative analysis of images. This work was supported by an American Heart Association Postdoctoral fellowship (15POST21870000 to A.I.M.), NIH F32HL117595 Postdoctoral Fellowship (C.C.O.), and an HHMI Gilliam Fellowship (D.M.B.). M.G. was supported by a fellowship from the American Heart Association (AHA). L.Z. was supported by a fellowship from the AHA (14POST20380738). W.Y.C. was supported by a fellowship from the NIH (F32 HL106987-02). This work was supported by grants from the NIH (HL127067 to C.E.B. and C.G.B., HL081674 to K.D.P., and AG040019 and HL117986 to R.T.L.). NR 53 TC 33 Z9 33 U1 5 U2 17 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 AUG 24 PY 2015 VL 34 IS 4 BP 387 EP 399 DI 10.1016/j.devcel.2015.06.017 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CQ1LP UT WOS:000360359500005 PM 26256209 ER PT J AU Phillips, CM Brown, KC Montgomery, BE Ruvkun, G Montgomery, TA AF Phillips, Carolyn M. Brown, Kristen C. Montgomery, Brooke E. Ruvkun, Gary Montgomery, Taiowa A. TI piRNAs and piRNA-Dependent siRNAs Protect Conserved and Essential C-elegans Genes from Misrouting into the RNAi Pathway SO DEVELOPMENTAL CELL LA English DT Article ID CAENORHABDITIS-ELEGANS; EPIGENETIC MEMORY; ARGONAUTE CSR-1; GERMLINE; PIWI; SPERMATOGENESIS; EXPRESSION; SEGREGATION; IMMORTALITY; GENERATION AB piRNAs silence foreign genes, such as transposons, to preserve genome integrity, but they also target endogenous mRNAs by mechanisms that are poorly understood. Caenorhabditis elegans piRNAs interact with both transposon and nontransposon mRNAs to initiate sustained silencing via the RNAi pathway. To assess the dysregulation of gene silencing caused by lack of piRNAs, we restored RNA silencing in RNAi-defective animals in the presence or absence of piRNAs. In the absence of piRNAs and a cellular memory of piRNA activity, essential and conserved genes are misrouted into the RNAi pathway to produce siRNAs that bind the nuclear Argonaute HRDE-1, resulting in dramatic defects in germ cell proliferation and function such that the animals are sterile. Inactivation of RNAi suppresses sterility, indicating that aberrant siRNAs produced in the absence of piRNAs target essential genes for silencing. Thus, by reanimating RNAi, we uncovered a role for piRNAs in protecting essential genes from RNA silencing. C1 [Phillips, Carolyn M.; Ruvkun, Gary] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. [Phillips, Carolyn M.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Brown, Kristen C.; Montgomery, Brooke E.; Montgomery, Taiowa A.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. [Brown, Kristen C.] Colorado State Univ, Cell & Mol Biol Program, Ft Collins, CO 80523 USA. RP Ruvkun, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu; tai.montgomery@colostate.edu RI Phillips, Carolyn/E-8305-2011; OI Phillips, Carolyn/0000-0002-6228-6468; Montgomery, Taiowa/0000-0001-7857-3253 FU NIH [GM044619, CA177897]; Colorado State University; University of Southern California; Massachusetts General Hospital Executive Committee of Research; Damon Runyon Cancer Research Foundation [DRG 1988-08, DRG 2029-09]; Boettcher Foundation FX Special thanks to Ulandt Kim for assistance with Illumina sequencing. Strains were provided by the CGC (NIH P40 OD010440), Shohei Mitani, and Craig Mello. HTP-3 antibody was provided by Abby Dernburg. This work was supported by the NIH (GM044619 to G.R. and CA177897 to C.M.P.), Colorado State University (T.A.M.), University of Southern California (C.M.P.), Massachusetts General Hospital Executive Committee of Research (C.M.P. and T.A.M.), Damon Runyon Cancer Research Foundation (DRG 1988-08 to C.M.P. and DRG 2029-09 to T.A.M.), and Boettcher Foundation (T.A.M.). NR 28 TC 3 Z9 3 U1 1 U2 8 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 AUG 24 PY 2015 VL 34 IS 4 BP 457 EP 465 DI 10.1016/j.devcel.2015.07.009 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CQ1LP UT WOS:000360359500011 PM 26279487 ER PT J AU Piazza, G Hohlfelder, B Jaff, MR Ouriel, K Engelhardt, TC Sterling, KM Jones, NJ Gurley, JC Bhatheja, R Kennedy, RJ Goswami, N Natarajan, K Rundback, J Sadiq, IR Liu, SK Bhalla, N Raja, ML Weinstock, BS Cynamon, J Elmasri, FF Garcia, MJ Kumar, M Ayerdi, J Soukas, P Kuo, W Liu, PY Goldhaber, SZ AF Piazza, Gregory Hohlfelder, Benjamin Jaff, Michael R. Ouriel, Kenneth Engelhardt, Tod C. Sterling, Keith M. Jones, Noah J. Gurley, John C. Bhatheja, Rohit Kennedy, Robert J. Goswami, Nilesh Natarajan, Kannan Rundback, John Sadiq, Immad R. Liu, Stephen K. Bhalla, Narinder Raja, M. Laiq Weinstock, Barry S. Cynamon, Jacob Elmasri, Fakhir F. Garcia, Mark J. Kumar, Mark Ayerdi, Juan Soukas, Peter Kuo, William Liu, Ping-Yu Goldhaber, Samuel Z. CA SEATTLE II Investigators TI A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism The SEATTLE II Study SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE catheter embolectomy; catheter thrombolysis; fibrinolysis; pulmonary embolism; right ventricular failure; thrombolysis ID PERCUTANEOUS MECHANICAL THROMBECTOMY; THROMBOLYTIC THERAPY; COMPUTED-TOMOGRAPHY; RANDOMIZED-TRIAL; METAANALYSIS; MANAGEMENT; RISK; EMBOLECTOMY; HEMORRHAGE; GUIDELINES AB OBJECTIVES This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). BACKGROUND Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. METHODS Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio >= 0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. RESULTS Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. CONCLUSIONS Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (C) 2015 by the American College of Cardiology Foundation. C1 [Piazza, Gregory; Hohlfelder, Benjamin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Jaff, Michael R.; Goldhaber, Samuel Z.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA USA. [Ouriel, Kenneth] Syntactx, New York, NY USA. [Engelhardt, Tod C.] East Jefferson Gen Hosp, Metairie, LA USA. [Sterling, Keith M.] INOVA Alexandria Hosp, Cardiovasc & Intervent Associates, Alexandria, VA USA. [Jones, Noah J.] Mt Carmel East Hosp, Columbus, OH USA. [Gurley, John C.] Univ Kentucky, Gill Heart Inst, Lexington, KY USA. [Bhatheja, Rohit] Florida Hosp, Florida Heart Grp, Orlando, FL USA. [Kennedy, Robert J.] Holmes Reg Med Ctr, Melbourne, FL USA. [Goswami, Nilesh] St Johns Hosp, Prairie Heart Inst, Springfield, IL USA. [Natarajan, Kannan] St Vincent Med Grp, Indianapolis, IN USA. [Rundback, John] Holy Name Med Ctr, Teaneck, NJ USA. [Sadiq, Immad R.] Hartford Hosp, Vasc Med Div, Hartford, CT 06115 USA. [Liu, Stephen K.] Mem Med Ctr, Lifelink Intervent Ctr, Modesto, CA USA. [Bhalla, Narinder] Baptist Med Ctr, River Reg Cardiol Associates, Montgomery, AL USA. [Raja, M. Laiq] Providence Mem Hosp, El Paso Cardiol Associates, PA, El Paso, TX USA. [Raja, M. Laiq] Sierra Med Hosp, El Paso, TX USA. [Weinstock, Barry S.] Leesburg Reg Med Ctr, Leesburg, FL USA. [Cynamon, Jacob] Montefiore Med Ctr, Div Vasc Intervent Radiol, Dept Radiol, Bronx, NY 10467 USA. [Elmasri, Fakhir F.] Lakeland Reg Med Ctr, Radiol & Imaging Specialists Lakeland, Lakeland, FL USA. [Garcia, Mark J.] Christiana Care Ctr Heart & Vasc Hlth, Newark, DE USA. [Kumar, Mark] Overlook Med Ctr, Cardiovasc Care Grp, Summit, NJ USA. [Ayerdi, Juan] Med Ctr Georgia, Macon Cardiovasc Inst, Macon, GA USA. [Soukas, Peter] Miriam Cardiol Inc, Miriam Hosp, Providence, RI USA. [Kuo, William] Stanford Univ, Stanford, CA 94305 USA. [Liu, Ping-Yu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Piazza, G (reprint author), Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM gpiazza@partners.org FU EKOS, a BTG International group company; Bristol-Myers Squibb; Daiichi-Sankyo; Janssen; Cordis; EKOS FX This study was funded by a research grant from EKOS, a BTG International group company. Dr. Piazza receives research support from EKOS, Bristol-Myers Squibb, Daiichi-Sankyo, and Janssen. Dr. Jaff is a noncompensated member of the Data Safety and Monitoring Board of EKOS and a Board member of VIVA Physicians, a 501(c)(3) not-for-profit education and research organization. Dr. Ouriel holds equity in and is an employee of Syntactx, which receives fees for core laboratory activities from EKOS. Dr. Jones receives honoraria for serving on the Speaker Bureau of Medtronic and EKOS; and receives consulting fees from Cordis. Drs. Engelhardt, Sterling, Gurley, Bhatheja, Kennedy, Goswami, Natarajan, Rundback, Sadiq, S.K. Liu, Bhalla, Raja, Weinstock, Cynamon, Elmasri, Garcia, Kumar, Ayerdi, Soukas, Kuo, and Goldhaber has received research support from EKOS, a BTG International Group company. Dr. P.-Y. Liu receives consulting fees from EKOS. Dr. Bhatheja is a speaker for St. Jude Medical and Cardiovascular Systems Inc. Dr. Goswami is a consultant for Boston Scientific. Dr. Gurley is a speaker for EKOS. Dr. Weinstock is a consultant for W.L. Gore. Dr. Hohfelder has reported that he has no relationships relevant to the contents of this paper to disclose. The results of this prospective, single-arm, multicenter trial were presented in abstract form on March 30, 2014 at the American College of Cardiology Annual Scientific Sessions in Washington, DC. NR 31 TC 45 Z9 45 U1 9 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD AUG 24 PY 2015 VL 8 IS 10 BP 1382 EP 1392 DI 10.1016/j.jcin.2015.04.020 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP6SD UT WOS:000360017500018 PM 26315743 ER PT J AU Liao, KP Ananthakrishnan, AN Kumar, V Xia, ZQ Cagan, A Gainer, VS Goryachev, S Chen, P Savova, GK Agniel, D Churchill, S Lee, JY Murphy, SN Plenge, RM Szolovits, P Kohane, I Shaw, SY Karlson, EW Cai, TX AF Liao, Katherine P. Ananthakrishnan, Ashwin N. Kumar, Vishesh Xia, Zongqi Cagan, Andrew Gainer, Vivian S. Goryachev, Sergey Chen, Pei Savova, Guergana K. Agniel, Denis Churchill, Susanne Lee, Jaeyoung Murphy, Shawn N. Plenge, Robert M. Szolovits, Peter Kohane, Isaac Shaw, Stanley Y. Karlson, Elizabeth W. Cai, Tianxi TI Methods to Develop an Electronic Medical Record Phenotype Algorithm to Compare the Risk of Coronary Artery Disease across 3 Chronic Disease Cohorts SO PLOS ONE LA English DT Article ID RHEUMATOID-ARTHRITIS; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; HEALTH RECORDS; PREDICTION; EQUIVALENT; EVENTS; ONSET AB Background Typically, algorithms to classify phenotypes using electronic medical record (EMR) data were developed to perform well in a specific patient population. There is increasing interest in analyses which can allow study of a specific outcome across different diseases. Such a study in the EMR would require an algorithm that can be applied across different patient populations. Our objectives were: (1) to develop an algorithm that would enable the study of coronary artery disease (CAD) across diverse patient populations; (2) to study the impact of adding narrative data extracted using natural language processing (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD algorithm to compare risk across 3 chronic diseases in a preliminary study. Methods and Results We studied 3 established EMR based patient cohorts: diabetes mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9 codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD algorithm using NLP in addition to structured data achieved specificity >95% with a positive predictive value (PPV) 90% in the training (RA) and validation sets (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts, classifying an additional 17% of CAD subjects in IBD and 10% in DM while maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was 63% lower in RA and 68% lower in IBD compared to DM(p<0.0001) after adjusting for traditional cardiovascular risk factors. Conclusions We developed and validated a CAD algorithm that performed well across diverse patient populations. The addition of NLP into the CAD algorithm improved the sensitivity of the algorithm, particularly in cohorts where the prevalence of CAD was low. Preliminary data suggest that CAD risk was significantly lower in RA and IBD compared to DM. C1 [Liao, Katherine P.; Plenge, Robert M.; Karlson, Elizabeth W.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Liao, Katherine P.; Ananthakrishnan, Ashwin N.; Kumar, Vishesh; Xia, Zongqi; Savova, Guergana K.; Murphy, Shawn N.; Plenge, Robert M.; Kohane, Isaac; Shaw, Stanley Y.; Karlson, Elizabeth W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Kumar, Vishesh; Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Xia, Zongqi] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Cagan, Andrew; Gainer, Vivian S.; Goryachev, Sergey] Partners Healthcare, Res Comp, Charlestown, MA 02125 USA. [Chen, Pei; Savova, Guergana K.; Kohane, Isaac; Cai, Tianxi] Boston Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA. [Agniel, Denis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Churchill, Susanne] Partners Healthcare Informat Syst, Boston, MA 02115 USA. [Lee, Jaeyoung] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plenge, Robert M.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Szolovits, Peter] MIT, CSAIL, Cambridge, MA 02139 USA. RP Liao, KP (reprint author), Brigham & Womens Hosp, Div Rheumatol, 75 Francis St, Boston, MA 02115 USA. EM kliao@partners.org OI Szolovits, Peter/0000-0001-8411-6403 FU National Institutes of Health (NIH) [U54LM008748]; NIH [K23 DK097142, K08 AR060257, K24 AR052403]; Harold and Duval Bowen Fund; Merck Research Laboratories FX All aspects of this study were funded by the National Institutes of Health (NIH) U54LM008748, Informatics for Integrating Biology and the Bedside Project (i2b2). ANA is supported by NIH K23 DK097142, KPL by NIH K08 AR060257 and the Harold and Duval Bowen Fund and EWK is supported by the NIH K24 AR052403. RMP is currently employed by Merck Research Laboratories. The majority of this study was conducted while RMP was a faculty member at Harvard Medical School and Brigham and Women's Hospital. RMP was employed at Merck during the drafting of the manuscript only. Merck Research Laboratories provided support in the form of salary for author RMP, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author is articulated in the 'author contributions' section. NR 26 TC 1 Z9 1 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 24 PY 2015 VL 10 IS 8 AR e0136651 DI 10.1371/journal.pone.0136651 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP5VA UT WOS:000359951900079 PM 26301417 ER PT J AU McCoy, TH Castro, VM Cagan, A Roberson, AM Kohane, IS Perlis, RH AF McCoy, Thomas H. Castro, Victor M. Cagan, Andrew Roberson, Ashlee M. Kohane, Isaac S. Perlis, Roy H. TI Sentiment Measured in Hospital Discharge Notes Is Associated with Readmission and Mortality Risk: An Electronic Health Record Study SO PLOS ONE LA English DT Article ID ENTERPRISE; DISORDERS; TWITTER AB Natural language processing tools allow the characterization of sentiment-that is, terms expressing positive and negative emotion-in text. Applying such tools to electronic health records may provide insight into meaningful patient or clinician features not captured in coded data alone. We performed sentiment analysis on 2,484 hospital discharge notes for 2,010 individuals from a psychiatric inpatient unit, as well as 20,859 hospital discharges for 15,011 individuals from general medical units, in a large New England health system between January 2011 and 2014. The primary measures of sentiment captured intensity of subjective positive or negative sentiment expressed in the discharge notes. Mean scores were contrasted between sociodemographic and clinical groups in mixed effects regression models. Discharge note sentiment was then examined for association with risk for readmission in Cox regression models. Discharge notes for individuals with greater medical comorbidity were modestly but significantly lower in positive sentiment among both psychiatric and general medical cohorts (p<0.001 in each). Greater positive sentiment at discharge was associated with significantly decreased risk of hospital readmission in each cohort (similar to 12% decrease per standard deviation above the mean). Automated characterization of discharge notes in terms of sentiment identifies differences between sociodemographic groups, as well as in clinical outcomes, and is not explained by differences in diagnosis. Clinician sentiment merits investigation to understand why and how it reflects or impacts outcomes. C1 [McCoy, Thomas H.; Castro, Victor M.; Cagan, Andrew; Roberson, Ashlee M.; Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [McCoy, Thomas H.; Castro, Victor M.; Cagan, Andrew; Roberson, Ashlee M.; Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Castro, Victor M.; Cagan, Andrew] Partners HealthCare Syst, Partners Res Comp, Constitut Ctr 1, Boston, MA 02129 USA. [Kohane, Isaac S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM rperlis@partners.org OI McCoy, Thomas/0000-0002-5624-0439 FU National Institute of Mental Health [1P50MH106933] FX This work was supported through funding from the National Institute of Mental Health (1P50MH106933). NR 25 TC 4 Z9 4 U1 2 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 24 PY 2015 VL 10 IS 8 AR e0136341 DI 10.1371/journal.pone.0136341 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP5VA UT WOS:000359951900061 PM 26302085 ER PT J AU Swisa, A Granot, Z Tamarina, N Sayers, S Bardeesy, N Philipson, L Hodson, DJ Wikstrom, JD Rutter, GA Leibowitz, G Glaser, B Dor, Y AF Swisa, Avital Granot, Zvi Tamarina, Natalia Sayers, Sophie Bardeesy, Nabeel Philipson, Louis Hodson, David J. Wikstrom, Jakob D. Rutter, Guy A. Leibowitz, Gil Glaser, Benjamin Dor, Yuval TI Loss of Liver Kinase B1 (LKB1) in Beta Cells Enhances Glucose-stimulated Insulin Secretion Despite Profound Mitochondrial Defects SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; DIRECT PHOSPHORYLATION; ENERGY-METABOLISM; PANCREATIC-ISLETS; SKELETAL-MUSCLE; GLUTAMATE ACTS; CANCER-CELLS; IN-VIVO; AMPK; MTOR AB The tumor suppressor liver kinase B1 (LKB1) is an important regulator of pancreatic beta cell biology. LKB1-dependent phosphorylation of distinct AMPK(adenosine monophosphate-activated protein kinase) family members determines proper beta cell polarity and restricts beta cell size, total beta cell mass, and glucose-stimulated insulin secretion (GSIS). However, the full spectrum of LKB1 effects and the mechanisms involved in the secretory phenotype remain incompletely understood. We report here that in the absence of LKB1 in beta cells, GSIS is dramatically and persistently improved. The enhancement is seen both in vivo and in vitro and cannot be explained by altered cell polarity, increased beta cell number, or increased insulin content. Increased secretion does require membrane depolarization and calcium influx but appears to rely mostly on a distal step in the secretion pathway. Surprisingly, enhanced GSIS is seen despite profound defects in mitochondrial structure and function in LKB1-deficient beta cells, expected to greatly diminish insulin secretion via the classic triggering pathway. Thus LKB1 is essential for mitochondrial homeostasis in beta cells and in parallel is a powerful negative regulator of insulin secretion. This study shows that beta cells can be manipulated to enhance GSIS to supra-normal levels even in the face of defective mitochondria and without deterioration over months. C1 [Swisa, Avital; Granot, Zvi; Dor, Yuval] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Dev Biol & Canc Res, Inst Med Res Israel Canada, IL-91120 Jerusalem, Israel. [Tamarina, Natalia; Philipson, Louis] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Sayers, Sophie; Hodson, David J.; Rutter, Guy A.] Univ London Imperial Coll Sci Technol & Med, Sect Cell Biol & Funct Genom, Div Diabet Endocrinol & Metab, Dept Med, London SW7 2AZ, England. [Bardeesy, Nabeel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Wikstrom, Jakob D.; Leibowitz, Gil; Glaser, Benjamin] Hadassah Hebrew Univ, Med Ctr, Dept Internal Med, Endocrinol & Metab Serv, IL-91120 Jerusalem, Israel. [Wikstrom, Jakob D.] Karolinska Univ Hosp, Karolinska Inst, Unit Dermatol & Venereol, Dept Med, S-17177 Stockholm, Sweden. RP Dor, Y (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Dev Biol & Canc Res, Inst Med Res Israel Canada, IL-91120 Jerusalem, Israel. EM yuvald@ekmd.huji.ac.il FU National Institutes of Health (NIDDK) [P60 DK20595]; Juvenile Diabetes Research Foundation; Beta Cell Biology Consortium; Helmsley Charitable Trust; European Research Commission (European Research Council consolidator grant); BIRAX; DON foundation; Israel Science Foundation; Israel Science Foundation [41.11]; USAID American Schools and Hospitals Abroad Program; Innovative Medicines Initiative Joint Undertaking [155005]; European Union's Seventh Framework Programme (FP7); Adams foundation; Ariane de Rothschild Women Doctoral Program; DiabetesUK [BDA 12/0004431]; Svenska Sallskapet for Medicinsk Forskning (SSMF); Royal Society Wolfson Research Merit Awards; MRC Programme [MR/J0003042/1]; Diabetes UK [11/0004210]; Biotechnology and Biological Sciences Research Council [BB/J015873/1]; [WT098424AIA] FX This work was supported, in whole or in part, by National Institutes of Health Grant P60 DK20595 (NIDDK; to P. I. Graeme Bell). This work was also supported by grants from the Juvenile Diabetes Research Foundation, Beta Cell Biology Consortium, The Helmsley Charitable Trust, the European Research Commission (European Research Council consolidator grant), BIRAX, the DON foundation, the Israel Science Foundation, and the I-CORE Program of The Israel Science Foundation #41.11 (to Y. D.). This work was also supported in part by a grant from USAID American Schools and Hospitals Abroad Program for the upgrading of the Hebrew University Medical School Flow Cytometry laboratory. The work leading to this publication received support from the Innovative Medicines Initiative Joint Undertaking under Grant 155005 (IMIDIA), resources of which are composed of a financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution (to G. A. R.). The authors declare that they have no conflicts of interest with the contents of this article.; Recipient of fellowships from the Adams foundation and the Ariane de Rothschild Women Doctoral Program.; Recipient of an R. D. Lawrence Fellowship from DiabetesUK (BDA 12/0004431).; Funded by a post-doctoral fellowship from the Svenska Sallskapet for Medicinsk Forskning (SSMF).; Supported by Wellcome Trust Senior Investigator (WT098424AIA) and Royal Society Wolfson Research Merit Awards, an MRC Programme (MR/J0003042/1), Diabetes UK (11/0004210), and Biotechnology and Biological Sciences Research Council (BB/J015873/1) project grants. NR 70 TC 6 Z9 6 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 2015 VL 290 IS 34 BP 20934 EP 20946 DI 10.1074/jbc.M115.639237 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CP6QC UT WOS:000360011800028 PM 26139601 ER PT J AU Nahrendorf, M Dutta, P AF Nahrendorf, Matthias Dutta, Partha TI Targeting splenic hematopoietic stem cells in cardiovascular disease SO ONCOTARGET LA English DT Editorial Material DE macrophage; hematopoietic stem cells; atherosclerosis ID ACUTE MYOCARDIAL-INFARCTION C1 [Dutta, Partha] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Dutta, Partha] Harvard Univ, Sch Med, Boston, MA USA. RP Dutta, P (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM dutta.partha@mgh.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 21 PY 2015 VL 6 IS 24 BP 19918 EP 19919 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CP8IY UT WOS:000360138200001 PM 26343366 ER PT J AU Namba, T Chu, K Kodama, R Byun, S Yoon, KW Hiraki, M Sam, AM Lee, SW AF Namba, Takushi Chu, Kiki Kodama, Rika Byun, Sanguine Yoon, Kyoung Wan Hiraki, Masatsugu Sam, Anna Mandinova Lee, Sam W. TI Loss of p53 enhances the function of the endoplasmic reticulum through activation of the IRE1 alpha/XBP1 pathway SO ONCOTARGET LA English DT Article DE tumor suppressor p53; p53 target genes; ER function; IRE1 alpha/XBP1 pathway ID UNFOLDED PROTEIN RESPONSE; UBIQUITIN LIGASE; ER STRESS; TUMOR-GROWTH; CANCER; DEGRADATION; METABOLISM; IRE1; ANGIOGENESIS; INHIBITION AB Altered regulation of ER stress response has been implicated in a variety of human diseases, such as cancer and metabolic diseases. Excessive ER function contributes to malignant phenotypes, such as chemoresistance and metastasis. Here we report that the tumor suppressor p53 regulates ER function in response to stress. We found that loss of p53 function activates the IRE1 alpha/XBP1 pathway to enhance protein folding and secretion through upregulation of IRE1 alpha and subsequent activation of its target XBP1. We also show that wild-type p53 interacts with synoviolin (SYVN1)/HRD1/DER3, a transmembrane E3 ubiquitin ligase localized to ER during ER stress and removes unfolded proteins by reversing transport to the cytosol from the ER, and its interaction stimulates IRE1 alpha degradation. Moreover, IRE1 alpha inhibitor suppressed protein secretion, induced cell death in p53-deficient cells, and strongly suppressed the formation of tumors by p53-deficient human tumor cells in vivo compared with those that expressed wild-type p53. Therefore, our data imply that the IRE1 alpha/XBP1 pathway serves as a target for therapy of chemoresistant tumors that express mutant p53. C1 [Namba, Takushi; Kodama, Rika] Kochi Univ, Ctr Sci Res, Nankoku, Kochi, Japan. [Namba, Takushi; Chu, Kiki; Byun, Sanguine; Yoon, Kyoung Wan; Hiraki, Masatsugu; Sam, Anna Mandinova; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Namba, Takushi; Chu, Kiki; Byun, Sanguine; Yoon, Kyoung Wan; Hiraki, Masatsugu; Sam, Anna Mandinova; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM t-namba@kochi-u.ac.jp; swlee@mgh.harvard.edu FU Japan Science and Technology Agency; Japan Society for the Promotion of Science; Takeda Science Foundation; NIH [CA80058, CA149477, CA142805] FX This work was partially supported by Grants-in-Aid of the Japan Science and Technology Agency, Japan Society for the Promotion of Science, Takeda Science Foundation and NIH grants: CA80058, CA149477, and CA142805. We thank the members of the Lee Laboratory for helpful advice and suggestions during the project. NR 33 TC 5 Z9 5 U1 0 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 AUG 21 PY 2015 VL 6 IS 24 BP 19990 EP 20001 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CP8IY UT WOS:000360138200028 PM 26254280 ER PT J AU Boland, GM Piha-Paul, SA Subbiah, V Routbort, M Herbrich, SM Baggerly, K Patel, KP Brusco, L Horombe, C Naing, A Fu, SQ Hong, DS Janku, F Johnson, A Broaddus, R Luthra, R Shaw, K Mendelsohn, J Mills, GB Meric-Bernstam, F AF Boland, Genevieve M. Piha-Paul, Sarina A. Subbiah, Vivek Routbort, Mark Herbrich, Shelley M. Baggerly, Keith Patel, Keyur P. Brusco, Lauren Horombe, Chacha Naing, Aung Fu, Siqing Hong, David S. Janku, Filip Johnson, Amber Broaddus, Russell Luthra, Raja Shaw, Kenna Mendelsohn, John Mills, Gordon B. Meric-Bernstam, Funda TI Clinical next generation sequencing to identify actionable aberrations in a phase I program SO ONCOTARGET LA English DT Article DE genomic sequencing; actionable genes ID CANCER-RELATED GENES; CELL LUNG-CANCER; COLORECTAL-CANCER; BREAST-CANCER; SOLID TUMORS; MUTATIONS AB Purpose: We determined the frequency of recurrent hotspot mutations in 46 cancer-related genes across tumor histologies in patients with advanced cancer. Methods: We reviewed data from 500 consecutive patients who underwent genomic profiling on an IRB-approved prospective clinical protocol in the Phase I program at the MD Anderson Cancer Center. Archival tumor DNA was tested for 740 hotspot mutations in 46 genes (Ampli-Seq Cancer Panel; Life Technologies, CA). Results: Of the 500 patients, 362 had at least one reported mutation/variant. The most common likely somatic mutations were within TP53 (36%), KRAS (11%), and PIK3CA (9%) genes. Sarcoma (20%) and kidney (30%) had the lowest proportion of likely somatic mutations detected, while pancreas (100%), colorectal (89%), melanoma (86%), and endometrial (75%) had the highest. There was high concordance in 62 patients with paired primary tumors and metastases analyzed. 151 (30%) patients had alterations in potentially actionable genes. 37 tumor types were enrolled; both rare actionable mutations in common tumor types and actionable mutations in rare tumor types were identified. Conclusion: Multiplex testing in the CLIA environment facilitates genomic characterization across multiple tumor lineages and identification of novel opportunities for genotype-driven trials. C1 [Boland, Genevieve M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol,Dept Surg, Boston, MA USA. [Boland, Genevieve M.; Meric-Bernstam, Funda] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Piha-Paul, Sarina A.; Subbiah, Vivek; Brusco, Lauren; Naing, Aung; Fu, Siqing; Hong, David S.; Janku, Filip; Meric-Bernstam, Funda] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA. [Routbort, Mark; Patel, Keyur P.; Luthra, Raja] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Herbrich, Shelley M.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Baggerly, Keith] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Horombe, Chacha; Johnson, Amber; Shaw, Kenna; Mendelsohn, John; Mills, Gordon B.; Meric-Bernstam, Funda] Univ Texas MD Anderson Canc Ctr, Dept Sheikh Khalifa Bin Zayed Al Nahyan, Inst Personalized Canc Therapy, Houston, TX 77030 USA. [Broaddus, Russell] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. RP Meric-Bernstam, F (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. EM fmeric@mdanderson.org RI Mendelsohn, John/K-6864-2016 FU Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy; NCI [5T32CA009599, 1U01 CA180964]; NCATS [UL1 TR000371]; Nellie B. Connally Breast Cancer Research Endowment; Bosarge Family Foundation; MD Anderson Cancer Center [P30 CA016672] FX This work was supported in part by the Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy, NCI 5T32CA009599, 1U01 CA180964, NCATS grant UL1 TR000371 (Center for Clinical and Translational Sciences), The Nellie B. Connally Breast Cancer Research Endowment, The Bosarge Family Foundation, and the MD Anderson Cancer Center Support grant (P30 CA016672). NR 21 TC 10 Z9 10 U1 0 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 21 PY 2015 VL 6 IS 24 BP 20099 EP 20110 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CP8IY UT WOS:000360138200036 PM 26015395 ER PT J AU Jenkins, CR Postma, DS Anzueto, AR Make, BJ Peterson, S Eriksson, G Calverley, PM AF Jenkins, Christine R. Postma, Dirkje S. Anzueto, Antonio R. Make, Barry J. Peterson, Stefan Eriksson, Goran Calverley, Peter M. TI Reliever salbutamol use as a measure of exacerbation risk in chronic obstructive pulmonary disease SO BMC PULMONARY MEDICINE LA English DT Article DE COPD; Budesonide/formoterol; Exacerbation; Reliever medication; Predictor ID METERED-DOSE INHALER; SEVERE COPD; CLINICAL-TRIAL; ASTHMA CONTROL; HEALTH-STATUS; EFFICACY; BUDESONIDE/FORMOTEROL; TIOTROPIUM; MODERATE; THERAPY AB Background: Debate exists regarding which endpoints most sensitively reflect day-to-day variation in chronic obstructive pulmonary disease (COPD) symptoms and are most useful in clinical practice to predict COPD exacerbations. We hypothesized that short-acting beta(2)-agonist (SABA) reliever use would predict short-and long-term exacerbation risk in COPD patients. Methods: We performed a retrospective analysis of data from a study (ClinicalTrials.govregistration: NCT00419744) comparing budesonide/formoterol 320/9 mu g with formoterol 9 mu g (both twice daily) in patients with moderate-to-very-severe COPD; reliever salbutamol 90 mu g was provided. First occurrence of reliever use >4 (low), >10 (medium), and >20 (high) inhalations/day was assessed as a predictor of short-term (3-week) exacerbation risk. Mean daily reliever use in the week preceding the 2-month visit was investigated as a predictor of the long-term (10-month) exacerbation risk, using intervals of 2-5, 6-9, and = 10 inhalations/day. Results: Overall, 810 patients were included (61 % male; mean age 63.2 years; post-bronchodilator forced expiratory volume in 1 s 37.7 % of predicted). First occurrence of low, medium, or high reliever use was predictive of an exacerbation within the following 3 weeks; exacerbation risk increased significantly with increasing reliever use. Mean reliever use over 1 week was predictive of long-term exacerbation risk. Patients with mean use of 2-5, 6-9, and = 10 inhalations/day exhibited 21 %, 67 %, and 135 % higher exacerbation rates, respectively, in the following 10 months, compared with <2 inhalations/day. Budesonide/formoterol was associated with lower short-and long-term exacerbation risk than formoterol in all reliever-use groups. Conclusions: SABA reliever use is a predictor of short-and long-term exacerbation risk in moderate-to-very-severe COPD patients with a history of exacerbations receiving budesonide/formoterol or formoterol. C1 [Jenkins, Christine R.] Univ Sydney, Concord Hosp, Dept Thorac Med, Sydney, NSW 2139, Australia. [Jenkins, Christine R.] George Inst Global Hlth, Sydney, NSW 2139, Australia. [Postma, Dirkje S.] Univ Groningen, Univ Med Ctr Groningen, Dept Pulm Med & TB, NL-9700 RB Groningen, Netherlands. [Anzueto, Antonio R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Pulm Sect, San Antonio, TX 78229 USA. [Anzueto, Antonio R.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Make, Barry J.] Univ Colorado, Denver Sch Med, Natl Jewish Hlth, Div Pulm Sci & Crit Care Med, Denver, CO 80206 USA. [Peterson, Stefan] Medicon Village AB, StatMind, S-22363 Lund, Sweden. [Eriksson, Goran] Univ Lund Hosp, Dept Resp Med & Allergol, S-22187 Lund, Sweden. [Calverley, Peter M.] Aintree Univ Hosp NHS Fdn Trust, Inst Ageing & Chron Dis, Clin Sci Dept, Liverpool L9 7AL, Merseyside, England. RP Jenkins, CR (reprint author), Univ Sydney, Concord Hosp, Dept Thorac Med, Hosp Rd, Sydney, NSW 2139, Australia. EM christine.jenkins@sydney.edu.au FU AstraZeneca FX AstraZeneca funded the analysis and were responsible for data collection and analysis of this post-hoc analysis. The authors thank Malin Fageras and Magnus Lindberg of AstraZeneca R&D, Molndal, Sweden, and Thomas Similowski of Service de Pneumologie et Reanimation Medicale, Paris, France, for their assistance with the development of this manuscript. Anna Mett and Shaun Foley of inScience Communications, Springer Healthcare, provided medical writing assistance, funded by AstraZeneca. NR 29 TC 2 Z9 2 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2466 J9 BMC PULM MED JI BMC Pulm. Med. PD AUG 21 PY 2015 VL 15 AR 97 DI 10.1186/s12890-015-0077-0 PG 9 WC Respiratory System SC Respiratory System GA CP7BP UT WOS:000360042500001 PM 26293575 ER PT J AU Carroll, JB Deik, A Fossale, E Weston, RM Guide, JR Arjomand, J Kwak, S Clish, CB MacDonald, ME AF Carroll, Jeffrey B. Deik, Amy Fossale, Elisa Weston, Rory M. Guide, Jolene R. Arjomand, Jamshid Kwak, Seung Clish, Clary B. MacDonald, Marcy E. TI Hdh(Q111) Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation SO PLOS ONE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HEPATIC MITOCHONDRIAL DYSFUNCTION; PREMANIFEST HUNTINGTONS-DISEASE; ENERGY-METABOLISM; IN-VIVO; WEIGHT-LOSS; HD; NEURODEGENERATION; EXPRESSION; PATHWAY AB The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ(111/+) mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue), using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219) in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant Hdh(Q111) striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and most evident in brain, where the striatum featured signature accumulation of a set of lipids including sphingomyelin, phosphatidylcholine, cholesterol ester and triglyceride species. Importantly, in the presence of the CAG mutation, metabolite changes were unmasked in peripheral tissues by an interaction with dietary fat, implying that the design of studies to discover metabolic changes in HD mutation carriers should include metabolic perturbations. C1 [Carroll, Jeffrey B.; Fossale, Elisa; Guide, Jolene R.; MacDonald, Marcy E.] Harvard Univ, Sch Med, Dept Neurol, Ctr Human Genet Res,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Carroll, Jeffrey B.; Weston, Rory M.] Western Washington Univ, Dept Psychol, Behav Neurosci Program, Bellingham, WA 98225 USA. [Deik, Amy; Fossale, Elisa; Clish, Clary B.; MacDonald, Marcy E.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Arjomand, Jamshid; Kwak, Seung] CHDI Fdn Inc, Princeton, NJ USA. RP Carroll, JB (reprint author), Harvard Univ, Sch Med, Dept Neurol, Ctr Human Genet Res,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM jeff.carroll@wwu.edu FU National Institute of Health [MEM: NS32765]; CHDI Foundation Inc. (MEM) FX Funding for this work was provided by the National Institute of Health (MEM: NS32765); CHDI Foundation Inc. (MEM). CHDI Foundation is also the employer of two authors (JA and SK). Beyond their intellectual contributions to the design of the study, foundation staff did not play a role in the data analysis, primary figure or manuscript drafting, or the decision to publish this manuscript. NR 58 TC 0 Z9 0 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 21 PY 2015 VL 10 IS 8 AR e0134465 DI 10.1371/journal.pone.0134465 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP5MR UT WOS:000359926900011 PM 26295712 ER PT J AU Naftulin, JS Kimchi, EY Cash, SS AF Naftulin, Jason S. Kimchi, Eyal Y. Cash, Sydney S. TI Streamlined, Inexpensive 3D Printing of the Brain and Skull SO PLOS ONE LA English DT Article ID TISSUE REGENERATION; MODELS; RECONSTRUCTION; FABRICATION; SCAFFOLDS; ACCURACY; HAND AB Neuroimaging technologies such as Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) collect three-dimensional data (3D) that is typically viewed on two-dimensional (2D) screens. Actual 3D models, however, allow interaction with real objects such as implantable electrode grids, potentially improving patient specific neurosurgical planning and personalized clinical education. Desktop 3D printers can now produce relatively inexpensive, good quality prints. We describe our process for reliably generating life-sized 3D brain prints from MRIs and 3D skull prints from CTs. We have integrated a standardized, primarily open-source process for 3D printing brains and skulls. We describe how to convert clinical neuroimaging Digital Imaging and Communications in Medicine (DICOM) images to stereolithography (STL) files, a common 3D object file format that can be sent to 3D printing services. We additionally share how to convert these STL files to machine instruction gcode files, for reliable in-house printing on desktop, open-source 3D printers. We have successfully printed over 19 patient brain hemispheres from 7 patients on two different open-source desktop 3D printers. Each brain hemisphere costs approximately $3-4 in consumable plastic filament as described, and the total process takes 14-17 hours, almost all of which is unsupervised (preprocessing = 4-6 hr; printing = 9-11 hr, post-processing = < 30 min). Printing a matching portion of a skull costs $1-5 in consumable plastic filament and takes less than 14 hr, in total. We have developed a streamlined, cost-effective process for 3D printing brain and skull models. We surveyed healthcare providers and patients who confirmed that rapid-prototype patient specific 3D models may help interdisciplinary surgical planning and patient education. The methods we describe can be applied for other clinical, research, and educational purposes. C1 [Naftulin, Jason S.; Kimchi, Eyal Y.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kimchi, Eyal Y.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA USA. RP Kimchi, EY (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM ekimchi@partners.org FU National Institute of Neurological Disorders and Stroke [T32-NS048005, R01-NS062092] FX This study was funded by grants from the National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/) (T32-NS048005 EYK, R01-NS062092 SSC). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 8 Z9 8 U1 6 U2 79 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 AUG 21 PY 2015 VL 10 IS 8 AR e0136198 DI 10.1371/journal.pone.0136198 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP5MR UT WOS:000359926900081 PM 26295459 ER PT J AU Peterson, KE Spadano-Gasbarro, JL Greaney, ML Austin, SB Mezgebu, S Hunt, AT Blood, EA Horan, C Feldman, HA Osganian, SK Bettencourt, MF Richmond, TK AF Peterson, Karen E. Spadano-Gasbarro, Jennifer L. Greaney, Mary L. Austin, S. Bryn Mezgebu, Solomon Hunt, Anne T. Blood, Emily A. Horan, Chrissy Feldman, Henry A. Osganian, Stavroula K. Bettencourt, Maria F. Richmond, Tracy K. TI Three-Year Improvements in Weight Status and Weight-Related Behaviors in Middle School Students: The Healthy Choices Study SO PLOS ONE LA English DT Article ID OBESITY PREVENTION PROGRAMS; PHYSICAL-ACTIVITY; PEDIATRIC OVERWEIGHT; CHILDHOOD OBESITY; PLANET-HEALTH; INTERVENTIONS; FRAMEWORK; IMPLEMENTATION; NUTRITION; PROMOTION AB Introduction Few dissemination evaluations exist to document the effectiveness of evidence-based childhood obesity interventions outside the research setting. Objective Evaluate Healthy Choices (HC), a multi-component obesity prevention program, by examining school-level changes in weight-related behaviors and weight status and the association of implementation components with odds of overweight/obesity. Methods We compared baseline and Year 3 school-level behavioral and weight status outcomes with paired t-tests adjusted for schools' socio-demographic characteristics. We used generalized estimating equations to examine the odds of overweight/obesity associated with program components. Setting/Participants Consecutive sample of 45 of 51 middle schools participating in the HC program with complete baseline and follow-up survey data including a subsample of 35 schools with measured anthropomentry for 5,665 7th grade students. Intervention Schools developed a multi-disciplinary team and implemented an obesity prevention curriculum, before and after school activities, environmental and policy changes and health promotions targeting a 5-2-1 theme: eat >= 5 servings/day of fruits and vegetables (FV), watch <= 2 hours of television (TV) and participate in >= 1 hours/day of physical activity (PA) on most days Main Outcome Measures 1) School-level percent of students achieving targeted behaviors and percent overweight/obese; and 2) individual odds of overweight/obesity. Results The percent achieving behavioral goals over three years increased significantly for FV: 16.4 to 19.4 (p = 0.001), TV: 53.4 to 58.2 (p = 0.003) and PA: 37.1 to 39.9 (p = 0.02), adjusting for school size, baseline mean age and percent female, non-Hispanic White, and eligible for free and reduced price lunch. In 35 schools with anthropometry, the percent of overweight/obese 7th grade students decreased from 42.1 to 38.4 (p = 0.016). Having a team that met the HC definition was associated with lower odds of overweight/obesity (OR = 0.83, CI: 0.71-0.98). Conclusions and Relevance The HC multi-component intervention demonstrated three-year improvements in weight-related behaviors and weight status across diverse middle schools. Team building appears important to the program's effectiveness. C1 [Peterson, Karen E.] Univ Michigan, Sch Publ Hlth, Dept Nutr Sci, Ann Arbor, MI 48109 USA. [Peterson, Karen E.] Univ Michigan, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. [Peterson, Karen E.; Spadano-Gasbarro, Jennifer L.; Greaney, Mary L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Peterson, Karen E.; Austin, S. Bryn] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Greaney, Mary L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Greaney, Mary L.] Univ Rhode Isl, Dept Kinesiol, Kingston, RI 02881 USA. [Austin, S. Bryn; Richmond, Tracy K.] Boston Childrens Hosp, Div Adolescent & Young Adult Med, Dept Med, Boston, MA 02115 USA. [Mezgebu, Solomon] Tufts Univ, USDA, Nutr Program North East Reg, Boston, MA 02111 USA. [Hunt, Anne T.] Hunt Consulting Associates, Logan, UT USA. [Blood, Emily A.; Feldman, Henry A.; Osganian, Stavroula K.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA. [Blood, Emily A.; Feldman, Henry A.; Osganian, Stavroula K.] Harvard Univ, Sch Med, Boston, MA USA. [Horan, Chrissy] Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program, Boston, MA USA. [Horan, Chrissy] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Bettencourt, Maria F.] Massachusetts Dept Publ Hlth, Boston, MA USA. RP Richmond, TK (reprint author), Boston Childrens Hosp, Div Adolescent & Young Adult Med, Dept Med, Boston, MA 02115 USA. EM tracy.richmond@childrens.harvard.edu RI Dey, Kamalesh/E-6568-2017 FU Massachusetts Department of Public Health; International Nutrition Foundation, Inc.; Centers for Disease Control and Prevention [U58/CCU12282]; Leadership Education in Adolescent Health project, Maternal and Child Health Bureau, Health Resources and Services Administration [6T71-MC00009]; NIH Career Development Award [K01 HD058042] FX Funding for this project was provided by the Massachusetts Department of Public Health in collaboration with the International Nutrition Foundation, Inc. Additional funding was provided by cooperative agreement no. U58/CCU12282 with the Centers for Disease Control and Prevention. S. Bryn Austin and Tracy K. Richmond are supported by the Leadership Education in Adolescent Health project, Maternal and Child Health Bureau, Health Resources and Services Administration grant no. 6T71-MC00009. T.K. Richmond was supported by an NIH Career Development Award (K01 HD058042). Coauthor Anne Hunt is a paid statistical consultant operating under her own consulting firm, Hunt Consulting Associates. Hunt Consulting Associates had a role in the study design, data collection and analysis, decision to publish, and preparation of the manuscript through the participation of co-author Anne Hunt. The specific role of this author is articulated in the 'author contributions' section. NR 46 TC 0 Z9 0 U1 3 U2 23 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 AUG 21 PY 2015 VL 10 IS 8 AR e0134470 DI 10.1371/journal.pone.0134470 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP5MR UT WOS:000359926900012 PM 26295837 ER PT J AU Sunaguchi, N Yuasa, T Hirano, S Gupta, R Ando, M AF Sunaguchi, Naoki Yuasa, Tetsuya Hirano, Shin-ichi Gupta, Rajiv Ando, Masami TI In Vitro Validation of an Artefact Suppression Algorithm in X-Ray Phase-Contrast Computed Tomography SO PLOS ONE LA English DT Article ID DARK-FIELD; RECONSTRUCTION AB X-ray phase-contrast tomography can significantly increase the contrast-resolution of conventional attenuation-contrast imaging, especially for soft-tissue structures that have very similar attenuation. Just as in attenuation-based tomography, phase contrast tomography requires a linear dependence of aggregate beam direction on the incremental direction alteration caused by individual voxels along the path of the X-ray beam. Dense objects such as calcifications in biological specimens violate this condition. There are extensive beam deflection artefacts in the vicinity of such structures because they result in large distortion of wave front due to the large difference of refractive index; for such large changes in beam direction, the transmittance of the silicon analyzer crystal saturates and is no longer linearly dependent on the angle of refraction. This paper describes a method by which these effects can be overcome and excellent soft-tissue contrast of phase tomography can be preserved in the vicinity of such artefact-producing structures. C1 [Sunaguchi, Naoki] Gunma Univ, Grad Sch Engn, Kiryu, Gunma, Japan. [Yuasa, Tetsuya] Yamagata Univ, Grad Sch Engn & Sci, Yonezawa, Yamagata, Japan. [Hirano, Shin-ichi] Mercian Cleantec Corp, Fujisawa, Kanagawa, Japan. [Hirano, Shin-ichi] MiZ Corp, Kamakura, Kanagawa, Japan. [Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gupta, Rajiv] Harvard Univ, Sch Med, Boston, MA USA. [Ando, Masami] Tokyo Univ Sci, Res Inst Sci & Technol, Noda, Chiba 278, Japan. RP Sunaguchi, N (reprint author), Gunma Univ, Grad Sch Engn, Kiryu, Gunma, Japan. FU KEK [2008S2-002, 2014G-002]; Japanese Ministry of Education Science and Culture [23602002, 26350494, 26750142]; Mercian Cleantec Corporation; MiZ Corporation FX The experiment was performed under the auspices of KEK (2008S2-002, 2014G-002). This work was funded by the Japanese Ministry of Education Science and Culture (TY #23602002, TY #26350494, NS #26750142)https://www.jsps.go.jp/j-grantsinaid/. At the time of the study Mercian Cleantec Corporation and MiZ Corporation provided support in the form of a salary for author SH but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section. NR 21 TC 1 Z9 1 U1 0 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 AUG 21 PY 2015 VL 10 IS 8 AR e0135654 DI 10.1371/journal.pone.0135654 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP5MR UT WOS:000359926900038 PM 26295713 ER PT J AU Haney, CH Ausubel, FM AF Haney, Cara H. Ausubel, Frederick M. TI Plant microbiome blueprints A plant defense hormone shapes the root microbiome SO SCIENCE LA English DT Editorial Material C1 [Haney, Cara H.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Haney, Cara H.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Haney, CH (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM haney@molbio.mgh.harvard.edu FU NIDDK NIH HHS [P30 DK040561] NR 11 TC 4 Z9 4 U1 10 U2 65 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 AUG 21 PY 2015 VL 349 IS 6250 BP 788 EP 789 DI 10.1126/science.aad0092 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP4DR UT WOS:000359832700017 PM 26293938 ER PT J AU Hubbuch, JE Bennett, BW Dean, JC AF Hubbuch, Jill E. Bennett, Blake W. Dean, Jesse C. TI Proprioceptive feedback contributes to the adaptation toward an economical gait pattern SO JOURNAL OF BIOMECHANICS LA English DT Article; Proceedings Paper CT 7th World Congress of Biomechanics CY JUL 06-11, 2014 CL Boston, MA DE Gait adaptation; Metabolic cost; Muscle activity; Tendon vibration ID HUMAN WALKING; TENDON VIBRATION; ENERGY-EXPENDITURE; MUSCLE AFFERENTS; MECHANICAL POWER; ACHILLES-TENDON; STEP FREQUENCY; METABOLIC COST; LEVEL WALKING; SPEED AB Humans generally prefer gait patterns with a low metabolic cost, but it is unclear how such patterns are chosen. We have previously proposed that humans may use proprioceptive feedback to identify economical movement patterns. The purpose of the present experiments was to investigate the role of plantarflexor proprioception in the adaptation toward an economical gait pattern. To disrupt proprioception in some trials, we applied noisy vibration (randomly varying between 40-120 Hz) over the bilateral Achilles tendons while participants stood quietly or walked on a treadmill. For all 10 min walking trials, the treadmill surface was initially level before slowly increasing to a 2.5% incline midway through the trial without participant knowledge. During standing posture, noisy vibration increased sway, indicating decreased proprioception accuracy. While walking on a level surface, vibration did not significantly influence stride period or metabolic rate. However, vibration had clear effects for the first 23 min after the incline increase; vibration caused participants to walk with shorter stride periods, reduced medial gastrocnemius (MG) activity during mid-stance (30-65% stance), and increased MG activity during late-stance (65-100% stance). Over time, these metrics gradually converged toward the gait pattern without vibration. Likely as a result of this delayed adaptation to the new mechanical context, the metabolic rate when walking uphill was significantly higher in the presence of noisy vibration. These results may be explained by the disruption of proprioception preventing rapid identification of muscle activation patterns which allow the muscles to operate under favorable mechanical conditions with low metabolic demand. Published by Elsevier Ltd. C1 [Hubbuch, Jill E.; Bennett, Blake W.; Dean, Jesse C.] Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA. [Dean, Jesse C.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Dean, JC (reprint author), 77 President St,MSC 700, Charleston, SC 29425 USA. EM deaje@musc.edu OI Dean, Jesse/0000-0003-2034-4217 FU United States Department of Veterans Affairs Rehabilitation Research and Development Service [1 IK2 RX000750] FX This work was supported in part by a Career Development Award (1 IK2 RX000750) from the United States Department of Veterans Affairs Rehabilitation Research and Development Service. Study sponsors had no role in the study design, data collection, analysis and interpretation of data, writing of the manuscript, or the decision to submit the manuscript for publication. NR 47 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 EI 1873-2380 J9 J BIOMECH JI J. Biomech. PD AUG 20 PY 2015 VL 48 IS 11 SI SI BP 2925 EP 2931 DI 10.1016/j.jbiomech.2015.04.024 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA CV1DO UT WOS:000363993800014 PM 25935689 ER PT J AU McAvoy, K Besnard, A Sahay, A AF McAvoy, Kathleen Besnard, Antoine Sahay, Amar TI Adult hippocampal neurogenesis and pattern separation in DG: a role for feedback inhibition in modulating sparseness to govern population-based coding SO FRONTIERS IN SYSTEMS NEUROSCIENCE LA English DT Article DE dentate gyrus; adult hippocampal neurogenesis; pattern separation; interference; discrimination; generalization; sparseness; feed-back inhibition ID DENTATE GRANULE CELLS; ENHANCED SYNAPTIC PLASTICITY; CRITICAL PERIOD; CONTEXT DISCRIMINATION; GENERATED NEURONS; GYRUS; MEMORY; BORN; RAT; CA3 AB The dentate gyrus (DG) of mammals harbors neural stem cells that generate new dentate granule cells (DGCs) throughout life. Behavioral studies using the contextual fear discrimination paradigm have found that selectively augmenting or blocking adult hippocampal neurogenesis enhances or impairs discrimination under conditions of high, but not low, interference suggestive of a role in pattern separation. Although contextual discrimination engages population-based coding mechanisms underlying pattern separation such as global remapping in the DG and CA3, how adult hippocampal neurogenesis modulates pattern separation in the DG is poorly understood. Here, we propose a role for adult born DGCs in re activation coupled modulation of sparseness through feed-back inhibition to govern global remapping in the DG. C1 [McAvoy, Kathleen; Besnard, Antoine; Sahay, Amar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Sahay, Amar] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Sahay, Amar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Sahay, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, CPZN 4242,185 Cambridge St, Boston, MA 02114 USA. EM asahay@mgh.hanrard.edu FU NIMH NIH HHS [R01 MH104175] NR 81 TC 3 Z9 3 U1 2 U2 11 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 AUG 20 PY 2015 VL 9 AR 120 DI 10.3389/fnsys.2015.00120 PG 7 WC Neurosciences SC Neurosciences & Neurology GA CU9FO UT WOS:000363849900001 PM 26347621 ER PT J AU Kelley, RK Bardeesy, N AF Kelley, Robin K. Bardeesy, Nabeel TI Biliary Tract Cancers: Finding Better Ways to Lump and Split SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID GALLBLADDER CARCINOMA; HILAR CHOLANGIOCARCINOMA; ADJUVANT CHEMOTHERAPY; MOLECULAR SUBTYPE; BLADDER-CANCER; IDENTIFICATION; GEMCITABINE; RECURRENCE; MUTATIONS; EXOME C1 [Kelley, Robin K.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Kelley, Robin K.] Univ Calif San Francisco, Ctr Liver, San Francisco, CA 94143 USA. [Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Bardeesy, Nabeel] Harvard Univ, Sch Med, Boston, MA USA. RP Kelley, RK (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. EM katie.kelley@ucsf.edu FU NCI NIH HHS [P30 CA082103, P30CA082103, P50CA127003-06A1, R01 CA136567-05]; NIDDK NIH HHS [P30 DK026743] NR 29 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2015 VL 33 IS 24 BP 2588 EP U13 DI 10.1200/JCO.2015.61.6953 PG 5 WC Oncology SC Oncology GA CR9EB UT WOS:000361655000003 PM 26195717 ER PT J AU O'Sullivan, CC Bradbury, I Campbell, C Spielmann, M Perez, EA Joensuu, H Costantino, JP Delaloge, S Rastogi, P Zardavas, D Ballman, KV Holmes, E de Azambuja, E Piccart-Gebhart, M Zujewski, JA Gelber, RD AF O'Sullivan, Ciara C. Bradbury, Ian Campbell, Christine Spielmann, Marc Perez, Edith A. Joensuu, Heikki Costantino, Joseph P. Delaloge, Suzette Rastogi, Priya Zardavas, Dimitrios Ballman, Karla V. Holmes, Eileen de Azambuja, Evandro Piccart-Gebhart, Martine Zujewski, Jo Anne Gelber, Richard D. TI Efficacy of Adjuvant Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer and Tumors <= 2 cm: A Meta-Analysis of the Randomized Trastuzumab Trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PLUS TRASTUZUMAB; OPEN-LABEL; PERTUZUMAB; DOCETAXEL; WOMEN; EXPRESSION; PACLITAXEL; LAPATINIB; OUTCOMES; SAFETY AB Purpose We compared efficacy of trastuzumab versus no trastuzumab in patients with small (<= 2 cm) human epidermal growth factor receptor 2 (HER2) -positive breast cancer treated in randomized trials. Methods A meta-analysis was conducted using data from five of the six adjuvant trastuzumab trials. Efficacy end points were disease-free survival (DFS) and overall survival (OS). Separate analyses were prospectively planned for hormone receptor (HR) -positive and HR-negative cohorts. Random effect models and Yusuf-Peto fixed effects models assessed the impact of heterogeneity on baseline hazards and treatment effects across studies. Peto-Pike cumulative incidence estimates were stratified by study and nodal status. Results Median follow-up time was 8 years. For 2,263 patients with HR-positive disease, 8-year cumulative incidence rates comparing trastuzumab versus no trastuzumab were 17.3% versus 24.3% (P < .001) for DFS and 7.8% versus 11.6% (P = .005) for OS, respectively; for 1,092 HR-positive patients with zero or one positive lymph nodes, results were 12.7% versus 19.4% (P = .005) for DFS and 5.3% versus 7.4% (P = .12) for OS, respectively. For 1,957 patients with HR-negative disease, 8-year cumulative incidence rates were 24.0% versus 33.4% (P < .001) for DFS and 12.4% versus 21.2% (P < .001) for OS, respectively; for 1,040 HR-negative patients with zero or one positive lymph nodes, results were 20.4% versus 26.3% (P = .05) for DFS and 8.2% versus 12.2% (P = .084) for OS, respectively. Conclusion Women with HER2-positive tumors <= 2 cm in the randomized trastuzumab trials derived substantial DFS and OS benefit from adjuvant trastuzumab. Trastuzumab-treated patients with HR-positive disease and <= one positive lymph node may be candidates for trials assessing less aggressive treatment approaches. (C) 2015 by American Society of Clinical Oncology C1 [O'Sullivan, Ciara C.; Zujewski, Jo Anne] NCI, Bethesda, MD 20892 USA. [Campbell, Christine; Holmes, Eileen] Frontier Sci, Kingussie, Inverness, Scotland. [Spielmann, Marc; Delaloge, Suzette] Inst Cancerol Gustave Roussy, Villejuif, France. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. [Joensuu, Heikki] Helsinki Univ Hosp, Helsinki, Finland. [Joensuu, Heikki] Univ Helsinki, Helsinki, Finland. [Costantino, Joseph P.; Rastogi, Priya] Univ Pittsburgh, Pittsburgh, PA USA. [Zardavas, Dimitrios] Breast Int Grp, Rochester, MN USA. [Ballman, Karla V.] Mayo Clin, Rochester, MN USA. [de Azambuja, Evandro; Piccart-Gebhart, Martine] Inst Jules Bordet, B-1000 Brussels, Belgium. [de Azambuja, Evandro; Piccart-Gebhart, Martine] Univ Libre Bruxelles, Brussels, Belgium. [Gelber, Richard D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. RP O'Sullivan, CC (reprint author), NCI, Room 12N226,10 Ctr Dr, Bethesda, MD 20892 USA. EM ciara.o'sullivan@nih.gov FU NCI NIH HHS [P30 CA015083, U10 CA180844] NR 36 TC 14 Z9 14 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2015 VL 33 IS 24 BP 2600 EP U37 DI 10.1200/JCO.2015.60.8620 PG 11 WC Oncology SC Oncology GA CR9EB UT WOS:000361655000007 PM 26101239 ER PT J AU Lin, NU Guo, H Yap, JT Mayer, IA Falkson, CI Hobday, TJ Dees, EC Richardson, AL Nanda, R Rimawi, MF Ryabin, N Najita, JS Barry, WT Arteaga, CL Wolff, AC Krop, IE Winer, EP Van den Abbeele, AD AF Lin, Nancy U. Guo, Hao Yap, Jeffrey T. Mayer, Ingrid A. Falkson, Carla I. Hobday, Timothy J. Dees, E. Claire Richardson, Andrea L. Nanda, Rita Rimawi, Mothaffar F. Ryabin, Nicole Najita, Julie S. Barry, William T. Arteaga, Carlos L. Wolff, Antonio C. Krop, Ian E. Winer, Eric P. Van den Abbeele, Annick D. TI Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [F-18]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OPEN-LABEL; NEOADJUVANT LAPATINIB; CHEMOTHERAPY PLUS; TUMOR RESPONSE; THERAPY; CELLS; TRIAL; PET; RECOMMENDATIONS; MULTICENTER AB Purpose Lapatinib plus trastuzumab improves outcomes relative to lapatinib alone in heavily pretreated, human epidermal growth factor receptor 2-positive metastatic breast cancer (MBC). We tested the combination in the earlier-line setting and explored the predictive value of [F-18]fluorodeoxyglucose positron emission tomography ([F-18]FDG-PET) for clinical outcomes. Patients and Methods Two cohorts were enrolled (cohort 1: no prior trastuzumab for MBC and >= 1 year from adjuvant trastuzumab, if given; cohort 2: one to two lines of chemotherapy including trastuzumab for MBC and/or recurrence < 1 year from adjuvant trastuzumab). The primary end point was objective response rate by RECIST v1.0; secondary end points included clinical benefit rate (complete response plus partial response plus stable disease >= 24 weeks) and progression-free survival. [F-18]FDG-PET scans were acquired at baseline, week 1, and week 8. Associations between metabolic response and clinical outcomes were explored. Results Eighty-seven patients were registered (85 were evaluable for efficacy). The confirmed objective response rate was 50.0% (95% CI, 33.8% to 66.2%) in cohort 1 and 22.2% (95% CI, 11.3% to 37.3%) in cohort 2. Clinical benefit rate was 57.5% (95% CI, 40.9% to 73.0%) in cohort 1 and 40.0% (95% CI, 25.7% to 55.7%) in cohort 2. Median progression-free survival was 7.4 and 5.3 months, respectively. Lack of week-1 [F-18]FDG-PET/computed tomography ([F-18]FDG-PET/CT) response was associated with failure to achieve an objective response by RECIST (negative predictive value, 91% [95% CI, 74% to 100%] for cohort 1 and 91% [95% CI, 79% to 100%] for cohort 2). Conclusion Early use of lapatinib and trastuzumab is active in human epidermal growth factor receptor 2-positive MBC. Week-1 [F-18]FDG-PET/CT may allow selection of patients who can be treated with targeted regimens and spared the toxicity of chemotherapy. (C) 2015 by American Society of Clinical Oncology C1 [Lin, Nancy U.; Guo, Hao; Ryabin, Nicole; Najita, Julie S.; Barry, William T.; Krop, Ian E.; Winer, Eric P.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Richardson, Andrea L.; Van den Abbeele, Annick D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yap, Jeffrey T.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Mayer, Ingrid A.; Arteaga, Carlos L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Falkson, Carla I.] Univ Alabama Birmingham, Birmingham, AL USA. [Hobday, Timothy J.] Mayo Clin, Rochester, MN USA. [Dees, E. Claire] Univ N Carolina, Chapel Hill, NC USA. [Nanda, Rita] Univ Chicago, Chicago, IL 60637 USA. [Rimawi, Mothaffar F.] Baylor Coll Med, Houston, TX 77030 USA. [Wolff, Antonio C.] Johns Hopkins SidneyKimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Susan F Smith Ctr Womens Canc, 450 Brookline Ave, Boston, MA 02215 USA. EM nlin@partners.org RI Guo, Hao/E-8921-2015 OI Guo, Hao/0000-0003-1658-0989 FU AVON Foundation; Breast Cancer Research Foundation; Susan G. Komen for the Cure; GlaxoSmithKline; National Cancer Institute (NCI) Specialized Program of Research Excellence (SPORE) at Dana-Farber/Harvard Cancer Center [CA089393]; NCI SPORE Avon Supplement [CA089393-10S1]; Nancy and Randy Berry Junior Faculty Fund; Dunkin' Donuts Rising Star Program; CJL Foundation FX Supported by the AVON Foundation, Breast Cancer Research Foundation, Susan G. Komen for the Cure, GlaxoSmithKline, Grant No. CA089393 from the National Cancer Institute (NCI) Specialized Program of Research Excellence (SPORE) at Dana-Farber/Harvard Cancer Center, Grant No. CA089393-10S1 from the NCI SPORE Avon Supplement, The Nancy and Randy Berry Junior Faculty Fund (N.U.L.), Dunkin' Donuts Rising Star Program (N.U.L.), and the CJL Foundation (W.T.B.). NR 32 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2015 VL 33 IS 24 BP 2623 EP U71 DI 10.1200/JCO.2014.60.0353 PG 14 WC Oncology SC Oncology GA CR9EB UT WOS:000361655000010 PM 26169615 ER PT J AU Scagliotti, G von Pawel, J Novello, S Ramlau, R Favaretto, A Barlesi, F Akerley, W Orlov, S Santoro, A Spigel, D Hirsh, V Shepherd, FA Sequist, LV Sandler, A Ross, JS Wang, Q von Roemeling, R Shuster, D Schwartz, B AF Scagliotti, Giorgio von Pawel, Joachim Novello, Silvia Ramlau, Rodryg Favaretto, Adolfo Barlesi, Fabrice Akerley, Wallace Orlov, Sergey Santoro, Armando Spigel, David Hirsh, Vera Shepherd, Frances A. Sequist, Lecia V. Sandler, Alan Ross, Jeffrey S. Wang, Qiang von Roemeling, Reinhard Shuster, Dale Schwartz, Brian TI Phase III Multinational, Randomized, Double-Blind, Placebo-Controlled Study of Tivantinib (ARQ 197) Plus Erlotinib Versus Erlotinib Alone in Previously Treated Patients With Locally Advanced or Metastatic Nonsquamous Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TRANSITION FACTOR INHIBITOR; RECEPTOR TYROSINE KINASE; HEPATOCELLULAR-CARCINOMA; CYTOTOXIC ACTIVITY; MET INHIBITION; COMBINATION; CRIZOTINIB; TRIAL; CHEMOTHERAPY AB Purpose Tivantinib, a MET receptor tyrosine kinase inhibitor, demonstrated increased anticancer activity in preclinical and early clinical studies when combined with erlotinib. Our study aimed to confirm efficacy and safety of the combination in previously treated patients with non-small-cell lung cancer (NSCLC). Patients and Methods Patients with advanced nonsquamous NSCLC previously treated with one to two systemic regimens, including a platinum doublet, were randomly assigned at a 1:1 ratio to receive erlotinib 150 mg daily plus oral tivantinib 360 mg twice daily (E + T) or erlotinib plus placebo (E + P) until disease progression. Tumor specimens were evaluated for EGFR and KRAS mutations, MET expression, and MET gene amplification. The primary end point was overall survival (OS). Secondary and exploratory objectives included progression-free survival (PFS), OS in molecular subgroups, and safety. Results The study enrolled 1,048 patients and was discontinued for futility at the interim analysis. OS did not improve with E + T versus E + P (median OS, 8.5 v 7.8 months, respectively; hazard ratio [HR], 0.98; 95% CI, 0.84 to 1.15; P = .81), even though PFS increased (median PFS, 3.6 v 1.9 months; HR, 0.74; 95% CI, 0.62 to 0.89; P < .001). Exploratory subgroup analyses suggested OS improvement in patients with high MET expression (HR, 0.70; 95% CI, 0.49 to 1.01). Most common adverse events occurring with E + T versus E + P were rash (33.1% v 37.3%, respectively), diarrhea (34.6% v 41.0%), asthenia or fatigue (43.5% v 38.1%), and neutropenia (grade 3 to 4; 8.5% v 0.8%). Conclusion E + T was well tolerated and increased PFS but did not improve OS in the overall nonsquamous NSCLC population. (C) 2015 by American Society of Clinical Oncology C1 [Scagliotti, Giorgio; Novello, Silvia] Univ Turin, I-10043 Turin, Italy. [Favaretto, Adolfo] Ist Oncol Veneto, Padua, Italy. [Santoro, Armando] Ist Clin Humanitas, Milan, Italy. [von Pawel, Joachim] Asklepios Fachkliniken Munchen Gauting, Munich, Germany. [Ramlau, Rodryg] Poznan Univ Med Sci, Poznan, Poland. [Barlesi, Fabrice] Aix Marseille Univ, AP HM, Marseille, France. [Akerley, Wallace] Huntsman Canc Inst, Salt Lake City, UT USA. [Orlov, Sergey] St Petersburg State Med Univ, St Petersburg, Russia. [Spigel, David] Clin Locat, Nashville, TN USA. [Hirsh, Vera] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Shepherd, Frances A.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ross, Jeffrey S.] Fdn Med, Cambridge, England. [Schwartz, Brian] ArQule, Woburn, MA USA. [Sandler, Alan] Genentech Inc, San Francisco, CA 94080 USA. [Wang, Qiang; von Roemeling, Reinhard; Shuster, Dale] Daiichi Sankyo, Edison, NJ USA. RP Scagliotti, G (reprint author), Univ Turin, S Luigi Hosp, Dept Oncol, Reg Gonzole 10, I-10043 Turin, Italy. EM giorgio.scagliotti@unito.it FU ArQule and Daiichi Sankyo (Tokyo, Japan); Science Communications, Springer Healthcare FX Supported by ArQule and Daiichi Sankyo (Tokyo, Japan), which also funded editorial support provided by inScience Communications, Springer Healthcare. NR 36 TC 48 Z9 50 U1 3 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2015 VL 33 IS 24 BP 2667 EP + DI 10.1200/JCO.2014.60.7317 PG 10 WC Oncology SC Oncology GA CR9EB UT WOS:000361655000016 PM 26169611 ER PT J AU Martin-Doyle, W Orsola, A Bellmunt, J AF Martin-Doyle, William Orsola, Anna Bellmunt, Joaquim TI Depth of Invasion in High-Grade T1 Bladder Cancer: Added Value In Timely Cystectomy? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Martin-Doyle, William; Orsola, Anna; Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Bellmunt, Joaquim] Univ Hosp Mar IMIM, Barcelona, Spain. RP Martin-Doyle, W (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. EM joaquim_bellmunt@dfci.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2015 VL 33 IS 24 BP 2716 EP 2717 DI 10.1200/JCO.2015.62.5301 PG 2 WC Oncology SC Oncology GA CR9EB UT WOS:000361655000027 PM 26195703 ER PT J AU Ciurea, SO Zhang, MJ Bacigalupo, AA Bashey, A Appelbaum, FR Aljitawi, OS Armand, P Antin, JH Chen, JF Devine, SM Fowler, DH Luznik, L Nakamura, R O'Donnell, PV Perales, MA Pingali, SR Porter, DL Riches, MR Ringden, OTH Rocha, V Vij, R Weisdorf, DJ Champlin, RE Horowitz, MM Fuchs, EJ Eapen, M AF Ciurea, Stefan O. Zhang, Mei-Jie Bacigalupo, Andrea A. Bashey, Asad Appelbaum, Frederick R. Aljitawi, Omar S. Armand, Philippe Antin, Joseph H. Chen, Junfang Devine, Steven M. Fowler, Daniel H. Luznik, Leo Nakamura, Ryotaro O'Donnell, Paul V. Perales, Miguel-Angel Pingali, Sai Ravi Porter, David L. Riches, Marcie R. Ringden, Olle T. H. Rocha, Vanderson Vij, Ravi Weisdorf, Daniel J. Champlin, Richard E. Horowitz, Mary M. Fuchs, Ephraim J. Eapen, Mary TI Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; HLA-MISMATCHED/HAPLOIDENTICAL BLOOD; RISK HEMATOLOGIC MALIGNANCIES; GRAFT FAILURE; INTERNATIONAL BLOOD; COMPLETE REMISSION; OUTCOMES; ADULTS; FLUDARABINE AB We studied adults with acute myeloid leukemia (AML) after haploidentical (n = 192) and 8/8 HLA-matched unrelated donor (n = 1982) transplantation. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate, and posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88 received reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737 received reduced intensity conditioning regimens. In the myeloablative setting, day 30 neutrophil recovery was lower after haploidentical compared with matched unrelated donor transplants (90% vs 97%, P = .02). Corresponding rates after reduced intensity conditioning transplants were 93% and 96% (P = .25). In the myeloablative setting, 3-month acute grade 2-4 (16% vs 33%, P < .0001) and 3-year chronic GVHD (30% vs 53%, P < .0001) were lower after haploidentical compared with matched unrelated donor transplants. Similar differences were observed after reduced intensity conditioning transplants, 19% vs 28% (P = .05) and 34% vs 52% (P = .002). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 45% (95% CI, 36-54) and 50% (95% CI, 47-53) after haploidentical and matched unrelated donor transplants (P5.38). Corresponding rates after reduced intensity conditioning transplants were 46%(95% CI, 35-56) and 44% (95% CI, 0.40-47) (P = .71). Although statistical poweris limited, these data suggests that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation. C1 [Ciurea, Stefan O.; Pingali, Sai Ravi; Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. [Zhang, Mei-Jie; Chen, Junfang; Horowitz, Mary M.; Eapen, Mary] 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. [Bacigalupo, Andrea A.] IRCCS Azienda Osped Univ AOU San Martino IST, Dept Hematol, Genoa, Italy. [Bashey, Asad] Northside Hosp, Dept Med, Atlanta, GA USA. [Appelbaum, Frederick R.; O'Donnell, Paul V.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Aljitawi, Omar S.] Univ Kansas, Med Ctr, Dept Med, Kansas City, KS 66103 USA. [Armand, Philippe; Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Devine, Steven M.] Ohio State Univ, Dept Internal Med, Arthur C James Canc Hosp, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Fowler, Daniel H.] NCI, Expt Transplantat & Immunobiol, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Luznik, Leo; Fuchs, Ephraim J.] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Dept Med Hematol, Baltimore, MD USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA 91010 USA. [Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplantat Serv, New York, NY 10021 USA. [Porter, David L.] Univ Penn, Abramson Canc Ctr, Hematol Oncol, Philadelphia, PA 19104 USA. [Riches, Marcie R.] H Lee Moffitt Canc Ctr & Res Inst, Dept Med, Tampa, FL USA. [Ringden, Olle T. H.] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden. [Rocha, Vanderson] Churchill Hosp, Oxford OX3 7LJ, England. [Vij, Ravi] Washington Univ, Sch Med, Div Hematol & Oncol, St Louis, MO USA. [Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. RP Ciurea, SO (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, 1515 Holcombe Blvd,Unit 423, Houston, TX 77030 USA. EM sciurea@mdanderson.org FU National Institutes of Health National Cancer Institute, National Heart, Lung, and Blood Institute [U24-CA076518]; National Heart, Lung, and Blood Institute [5U10HL069294]; National Cancer Institute; Health Resources and Services Administration [HHSH250201200016C]; Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; 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; Medac GmbH; Medical College of Wisconsin; MerckCo,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.; PerkinElmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte; 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 a Public Health Service grant/cooperative agreement (U24-CA076518) from the National Institutes of Health National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases; a grant/cooperative agreement from the National Heart, Lung, and Blood Institute (5U10HL069294) and National Cancer Institute; a contract with Health Resources and Services Administration (HHSH250201200016C); grants from the Office of Naval Research (N00014-13-1-0039 and N00014-14-1-0028); and grants from the following: 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; 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.; PerkinElmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte; 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 Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government. NR 36 TC 71 Z9 74 U1 0 U2 3 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 AUG 20 PY 2015 VL 126 IS 8 BP 1033 EP 1040 DI 10.1182/blood-2015-04-639831 PG 8 WC Hematology SC Hematology GA CQ3WU UT WOS:000360535700023 PM 26130705 ER PT J AU Yang, HW Kim, TM Song, SS Menon, L Jiang, X Huang, W Black, PM Park, PJ Carroll, RS Johnson, MD AF Yang, H. W. Kim, T-M Song, S. S. Menon, L. Jiang, X. Huang, W. Black, P. M. Park, P. J. Carroll, R. S. Johnson, M. D. TI A small subunit processome protein promotes cancer by altering translation SO ONCOGENE LA English DT Article ID INTERNAL RIBOSOME ENTRY; MESSENGER-RNA; CHILDHOOD MEDULLOBLASTOMA; MYCN-AMPLIFICATION; C-MYC; NEUROBLASTOMA; SITE; REVEALS; HYPOXIA; CELLS AB Dysregulation of ribosome biogenesis or translation can promote cancer, but the underlying mechanisms remain unclear. UTP18 is a component of the small subunit processome, a nucleolar multi-protein complex whose only known function is to cleave pre-ribosomal RNA to yield the 18S ribosomal RNA component of 40S ribosomal subunits. Here, we show that UTP18 also alters translation to promote stress resistance and growth, and that UTP18 is frequently gained and overexpressed in cancer. We observed that UTP18 localizes to the cytoplasm in a subset of cells, and that serum withdrawal increases cytoplasmic UTP18 localization. Cytoplasmic UTP18 associates with the translation complex and Hsp90 to upregulate the translation of IRES-containing transcripts such as HIF1a, Myc and VEGF, thereby inducing stress resistance. Hsp90 inhibition decreases cytoplasmic UTP18 and UTP18-induced increases in translation. Importantly, elevated UTP18 expression correlates with increased aggressiveness and decreased survival in numerous cancers. Enforced UTP18 overexpression promotes transformation and tumorigenesis, whereas UTP18 knockdown inhibits these processes. This stress adaptation mechanism is thus co-opted for growth by cancers, and its inhibition may represent a promising new therapeutic target. C1 [Yang, H. W.; Song, S. S.; Menon, L.; Jiang, X.; Huang, W.; Black, P. M.; Carroll, R. S.; Johnson, M. D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Kim, T-M; Park, P. J.] Harvard Univ, Ctr Biomed Informat, Sch Med, Boston, MA 02115 USA. [Johnson, M. D.] Dana Farber Brigham & Womens Canc Ctr, Program Neurooncol, Boston, MA USA. RP Johnson, MD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. EM mjohnson27@partners.org FU Brain Science Foundation; Santos Family Foundation; National Institute of Neurological Disorders and Stroke [R01 NS062219]; NIH [DP2 OD002319] FX This work was supported by a Brain Science Foundation Research Award, the Santos Family Foundation, a Hagerty Fund Research Award, R01 NS062219 from the National Institute of Neurological Disorders and Stroke and an NIH Director's New Innovator Award (DP2 OD002319) to MDJ. NR 35 TC 1 Z9 1 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD AUG 20 PY 2015 VL 34 IS 34 BP 4471 EP 4481 DI 10.1038/onc.2014.376 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CP9BR UT WOS:000360189200006 PM 25435373 ER PT J AU Patai, AV Valcz, G Hollosi, P Kalmar, A Peterfia, B Patai, A Wichmann, B Spisak, S Bartak, BK Leiszter, K Toth, K Sipos, F Kovalszky, I Peter, Z Miheller, P Tulassay, Z Molnar, B AF Patai, Arpad V. Valcz, Gabor Hollosi, Peter Kalmar, Alexandra Peterfia, Balint Patai, Arpad Wichmann, Barnabas Spisak, Sandor Bartak, Barbara Kinga Leiszter, Katalin Toth, Kinga Sipos, Ferenc Kovalszky, Ilona Peter, Zoltan Miheller, Pal Tulassay, Zsolt Molnar, Bela TI Comprehensive DNA Methylation Analysis Reveals a Common Ten-Gene Methylation Signature in Colorectal Adenomas and Carcinomas SO PLOS ONE LA English DT Article ID FREQUENT EPIGENETIC INACTIVATION; COLON-CANCER; GENES; TUMOR; MARKER; HYPERMETHYLATION; CARCINOGENESIS; IDENTIFICATION; TUMORIGENESIS; PROGRESSION AB Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA methylation in the development of colorectal cancer (CRC) and may be co-monitored with the appearance of driver mutations. Colonic biopsy samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade (LGD) and 6 high-grade dysplasia (HGD)), and 8 ulcerative colitis (UC) patients (4 active and 4 inactive). CRC samples were obtained from 24 patients (17 primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue materials were studied for DNA methylation status using a 96 gene panel and for KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA arrays. SFRP1 was further examined by immunohistochemistry. HT29 cells were treated with 5-aza-2' deoxycytidine to analyze the reversal possibility of DNA methylation. More than 85% of tumor samples showed hypermethylation in 10 genes (SFRP1, SST, BNC1, MAL, SLIT2, SFRP2, SLIT3, ALDH1A3, TMEFF2, WIF1), whereas the frequency of examined mutations were below 25%. These genes distinguished precancerous and cancerous lesions from inflamed and healthy tissue. The mRNA alterations that might be caused by systematic methylation could be partly reversed by demethylation treatment. Systematic changes in methylation patterns were observed early in CRC carcinogenesis, occuring in precursor lesions and CRC. Thus we conclude that DNA hypermethylation is an early and systematic event in colorectal carcinogenesis, and it could be potentially reversed by systematic demethylation therapy, but it would need more in vitro and in vivo experiments to support this theory. C1 [Patai, Arpad V.; Kalmar, Alexandra; Bartak, Barbara Kinga; Leiszter, Katalin; Toth, Kinga; Sipos, Ferenc; Peter, Zoltan; Miheller, Pal; Tulassay, Zsolt; Molnar, Bela] Semmelweis Univ, Dept Med 2, H-1085 Budapest, Hungary. [Valcz, Gabor; Peterfia, Balint; Wichmann, Barnabas; Spisak, Sandor; Tulassay, Zsolt; Molnar, Bela] Hungarian Acad Sci, Mol Med Res Grp, Budapest, Hungary. [Hollosi, Peter; Kovalszky, Ilona] Semmelweis Univ, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. [Hollosi, Peter] Hungarian Acad Sci, Tumor Progress Res Grp, Budapest, Hungary. [Patai, Arpad] Markusovszky Univ Teaching Hosp, Dept Gastroenterol & Med, Szombathely, Hungary. [Spisak, Sandor] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Patai, AV (reprint author), Semmelweis Univ, Dept Med 2, H-1085 Budapest, Hungary. EM arpad.patai@gmail.com FU National Office for Research and Technology, Hungary [TECH_08-A1/2-2008-0114]; Hungarian Scientific Research Fund (OTKA) [K 111743] FX This study was supported by the National Office for Research and Technology, Hungary, (Grant number: TECH_08-A1/2-2008-0114) and by the Hungarian Scientific Research Fund (OTKA, Grant number: K 111743, www.magzrt.hu and www.otka.hu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 5 Z9 5 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 20 PY 2015 VL 10 IS 8 AR e0133836 DI 10.1371/journal.pone.0133836 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP5KH UT WOS:000359919900003 PM 26291085 ER PT J AU Perera, R Stoykova, S Nicolay, BN Ross, KN Fitamant, J Boukhali, M Lengrand, J Deshpande, V Selig, MK Ferrone, CR Settleman, J Stephanopoulos, G Dyson, NJ Zoncu, R Ramaswamy, S Haas, W Bardeesy, N AF Perera, RushikaM. Stoykova, Svetlana Nicolay, Brandon N. Ross, Kenneth N. Fitamant, Julien Boukhali, Myriam Lengrand, Justine Deshpande, Vikram Selig, Martin K. Ferrone, Cristina R. Settleman, Jeff Stephanopoulos, Gregory Dyson, Nicholas J. Zoncu, Roberto Ramaswamy, Sridhar Haas, Wilhelm Bardeesy, Nabeel TI Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism SO NATURE LA English DT Article ID NUCLEAR IMPORT; GENOMIC ANALYSES; TUMOR-GROWTH; PROTEIN; BIOGENESIS; CELLS; MTOR; TFEB; P53; CLEARANCE AB Activation of cellular stress response pathways to maintain metabolic homeostasis is emerging as a critical growth and survival mechanism in many cancers(1). The pathogenesis of pancreatic ductal adenocarcinoma (PDA) requires high levels of autophagy(2-4), a conserved self-degradative process(5). However, the regulatory circuits that activate autophagy and reprogram PDA cell metabolism are unknown. Here we show that autophagy induction in PDA occurs as part of a broader transcriptional program that coordinates activation of lysosome biogenesis and function, and nutrient scavenging, mediated by the MiT/TFE family of transcription factors. In human PDA cells, the MiT/TFE proteins(6)-MITF, TFE3 and TFEB-are decoupled from regulatory mechanisms that control their cytoplasmic retention. Increased nuclear import in turn drives the expression of a coherent network of genes that induce high levels of lysosomal catabolic function essential for PDA growth. Unbiased global metabolite profiling reveals that MiT/TFE-dependent autophagy-lysosome activation is specifically required to maintain intracellular amino acid pools. These results identify the MiT/TFE proteins as master regulators of metabolic reprogramming in pancreatic cancer and demonstrate that transcriptional activation of clearance pathways converging on the lysosome is a novel hallmark of aggressive malignancy. C1 [Perera, RushikaM.; Stoykova, Svetlana; Nicolay, Brandon N.; Ross, Kenneth N.; Fitamant, Julien; Boukhali, Myriam; Lengrand, Justine; Ferrone, Cristina R.; Settleman, Jeff; Dyson, Nicholas J.; Ramaswamy, Sridhar; Haas, Wilhelm; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Perera, RushikaM.; Stoykova, Svetlana; Ross, Kenneth N.; Fitamant, Julien; Lengrand, Justine; Ramaswamy, Sridhar; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Perera, RushikaM.; Nicolay, Brandon N.; Ross, Kenneth N.; Fitamant, Julien; Deshpande, Vikram; Ferrone, Cristina R.; Dyson, Nicholas J.; Ramaswamy, Sridhar; Haas, Wilhelm; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Deshpande, Vikram; Selig, Martin K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Zoncu, Roberto] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Bardeesy, N (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. EM Bardeesy.Nabeel@MGH.Harvard.edu RI di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 FU National Institutes of Health [P50CA1270003, P01 CA117969-07, R01 CA133557-05]; Linda J. Verville Cancer Research Foundation; Hirshberg Foundation for Pancreatic Cancer FX We would like to thank A. Kimmelman, L. Ellisen, W. Kim and R. Mostoslavsky for advice and helpful comments on the manuscript, S. Gygi for access to proteomics data analysis software, F. Kottakis, Y. Mizukami and M. Leisa for technical support, and C. Ivan for bioinformatics support. This work was supported by grants from the National Institutes of Health (P50CA1270003, P01 CA117969-07, R01 CA133557-05) and the Linda J. Verville Cancer Research Foundation to N.B. N.B. holds the Gallagher Endowed Chair in Gastrointestinal Cancer Research. R.M.P. holds a Hirshberg Foundation for Pancreatic Cancer seed grant. N.B. and R.M.P. are members of the Andrew Warshaw Institute for Pancreatic Cancer Research. NR 46 TC 74 Z9 74 U1 17 U2 59 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 AUG 20 PY 2015 VL 524 IS 7565 BP 361 EP U251 DI 10.1038/nature14587 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP2NN UT WOS:000359714000038 PM 26168401 ER PT J AU Naggie, S Cooper, C Saag, M Workowski, K Ruane, P Towner, WJ Marks, K Luetkemeyer, A Baden, RP Sax, PE Gane, E Santana-Bagur, J Stamm, LM Yang, JC German, P Dvory-Sobol, H Ni, LY Pang, PS McHutchison, JG Stedman, CAM Morales-Ramirez, JO Brau, N Jayaweera, D Colson, AE Tebas, P Wong, DK Dieterich, D Sulkowski, M AF Naggie, Susanna Cooper, Curtis Saag, Michael Workowski, Kimberly Ruane, Peter Towner, William J. Marks, Kristen Luetkemeyer, Anne Baden, Rachel P. Sax, Paul E. Gane, Edward Santana-Bagur, Jorge Stamm, Luisa M. Yang, Jenny C. German, Polina Dvory-Sobol, Hadas Ni, Liyun Pang, Phillip S. McHutchison, John G. Stedman, Catherine A. M. Morales-Ramirez, Javier O. Braeu, Norbert Jayaweera, Dushyantha Colson, Amy E. Tebas, Pablo Wong, David K. Dieterich, Douglas Sulkowski, Mark CA ION-4 Investigators TI Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEPATITIS-C VIRUS; GENOTYPE 1 INFECTION; ALPHA-2A PLUS RIBAVIRIN; HEPATOCELLULAR-CARCINOMA; LIVER-DISEASE; INTERFERON; CIRRHOSIS; THERAPY; COHORT; VETERANS AB BACKGROUND Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need. METHODS We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 virologic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events. CONCLUSIONS Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; C1 [Naggie, Susanna] Duke Clin Res Inst, Durham, NC 27705 USA. [Cooper, Curtis] Univ Ottawa, Ottawa Hosp, Ottawa, ON, Canada. [Wong, David K.] Univ Toronto, Toronto Gen Hosp, Dept Hepatol, Immunodeficiency Clin, Toronto, ON M5G 1L7, Canada. [Saag, Michael] Univ Alabama Birmingham, Birmingham, AL USA. [Workowski, Kimberly] Emory Univ, Emory Healthcare, Atlanta, GA 30322 USA. [Ruane, Peter] Ruane Med & Liver Hlth Inst, Los Angeles, CA USA. [Towner, William J.] Kaiser Permanente, Los Angeles Med Ctr, Los Angeles, CA USA. [Luetkemeyer, Anne] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA USA. [Stamm, Luisa M.; Yang, Jenny C.; German, Polina; Dvory-Sobol, Hadas; Ni, Liyun; Pang, Phillip S.; McHutchison, John G.] Gilead Sci, Foster City, CA USA. [Marks, Kristen] Weill Cornell Med Coll, New York, NY USA. [Braeu, Norbert; Dieterich, Douglas] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Braeu, Norbert] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Baden, Rachel P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sax, Paul E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sax, Paul E.] Harvard Univ, Sch Med, Boston, MA USA. [Colson, Amy E.] Community Res Initiat New England, Boston, MA USA. [Gane, Edward] Univ Auckland, Auckland City Hosp, Auckland 1, New Zealand. [Stedman, Catherine A. M.] Christchurch Hosp, Christchurch, New Zealand. [Stedman, Catherine A. M.] Univ Otago, Christchurch, New Zealand. [Santana-Bagur, Jorge] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Morales-Ramirez, Javier O.] Clin Res Puerto Rico, San Juan, PR USA. [Jayaweera, Dushyantha] Univ Miami, Miami, FL USA. [Tebas, Pablo] Univ Penn, Philadelphia, PA 19104 USA. [Sulkowski, Mark] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Naggie, S (reprint author), Duke Clin Res Inst, Infect Dis Sect, 2400 Pratt St, Durham, NC 27705 USA. EM susanna.naggie@duke.edu OI Wong, David/0000-0002-3310-3538 FU Gilead Sciences FX Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656. NR 26 TC 104 Z9 104 U1 4 U2 20 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 AUG 20 PY 2015 VL 373 IS 8 BP 705 EP 713 DI 10.1056/NEJMoa1501315 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CP2LU UT WOS:000359709400007 PM 26196665 ER PT J AU Hyman, DM Puzanov, I Subbiah, V Faris, JE Chau, I Blay, JY Wolf, J Raje, NS Diamond, EL Hollebecque, A Gervais, R Elez-Fernandez, ME Italiano, A Hofheinz, RD Hidalgo, M Chan, E Schuler, M Lasserre, SF Makrutzki, M Sirzen, F Veronese, ML Tabernero, J Baselga, J AF Hyman, David M. Puzanov, Igor Subbiah, Vivek Faris, Jason E. Chau, Ian Blay, Jean-Yves Wolf, Juergen Raje, Noopur S. Diamond, Eli L. Hollebecque, Antoine Gervais, Radj Elena Elez-Fernandez, Maria Italiano, Antoine Hofheinz, Ralf-Dieter Hidalgo, Manuel Chan, Emily Schuler, Martin Lasserre, Susan Frances Makrutzki, Martina Sirzen, Florin Veronese, Maria Luisa Tabernero, Josep Baselga, Jose TI Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ERDHEIM-CHESTER DISEASE; LANGERHANS CELL HISTIOCYTOSIS; METASTATIC COLORECTAL-CANCER; LUNG-CANCER; 1ST-LINE TREATMENT; HIGH PREVALENCE; CHEMOTHERAPY; TRIAL; EGFR; INHIBITION AB BACKGROUND BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 "basket" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers. METHODS We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival. RESULTS In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma. CONCLUSIONS BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers. C1 [Hyman, David M.; Diamond, Eli L.; Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Puzanov, Igor; Chan, Emily] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Subbiah, Vivek] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Faris, Jason E.; Raje, Noopur S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chau, Ian] Royal Marsden Hosp, Sutton, Surrey, England. [Blay, Jean-Yves] Ctr Leon Berard, F-69373 Lyon, France. [Hollebecque, Antoine] Inst Gustave Roussy, Villejuif, France. [Gervais, Radj] Ctr Hosp Univ Cote Nacre, Ctr Francois Baclesse, Caen, France. [Italiano, Antoine] Inst Bergonie Canc Ctr, Bordeaux, France. [Wolf, Juergen] Univ Hosp Cologne, Cologne, Germany. [Hofheinz, Ralf-Dieter] Univ Med Mannheim, Mannheim, Germany. [Schuler, Martin] Univ Hosp Essen, West Gerrman Canc Ctr, Essen, Germany. [Schuler, Martin] German Canc Consortium, Heidelberg, Germany. [Elena Elez-Fernandez, Maria; Tabernero, Josep] Vall Hebron Univ Hosp, Barcelona, Spain. [Elena Elez-Fernandez, Maria; Tabernero, Josep] Univ Autonoma Barcelona, Inst Oncol, E-08193 Barcelona, Spain. [Hidalgo, Manuel] Hosp Univ Madrid Sanchinarro, Madrid, Spain. [Lasserre, Susan Frances; Makrutzki, Martina; Sirzen, Florin; Veronese, Maria Luisa] F Hoffmann La Roche, Basel, Switzerland. RP Baselga, J (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM baselgaj@mskcc.org RI Blay, Jean-Yves/N-3966-2016; OI Blay, Jean-Yves/0000-0001-7190-120X; Diamond, Eli/0000-0001-5456-5961 FU F. Hoffmann-La Roche/Genentech FX Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT01524978. NR 33 TC 183 Z9 190 U1 5 U2 29 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 AUG 20 PY 2015 VL 373 IS 8 BP 726 EP 736 DI 10.1056/NEJMoa1502309 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CP2LU UT WOS:000359709400009 PM 26287849 ER PT J AU Sweeney, CJ Chen, YH Carducci, M Liu, G Jarrard, DF Eisenberger, M Wong, YN Hahn, N Kohli, M Cooney, MM Dreicer, R Vogelzang, NJ Picus, J Shevrin, D Hussain, M Garcia, JA DiPaola, RS AF Sweeney, Christopher J. Chen, Yu-Hui Carducci, Michael Liu, Glenn Jarrard, David F. Eisenberger, Mario Wong, Yu-Ning Hahn, Noah Kohli, Manish Cooney, Matthew M. Dreicer, Robert Vogelzang, Nicholas J. Picus, Joel Shevrin, Daniel Hussain, Maha Garcia, Jorge A. DiPaola, Robert S. TI Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PHASE-III TRIAL; ANDROGEN-DEPRIVATION; INCREASED SURVIVAL; OPEN-LABEL; DOCETAXEL; CHEMOTHERAPY; MITOXANTRONE; CASTRATION; PREDNISONE; CARCINOMA AB BACKGROUND Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone. METHODS We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone. RESULTS A total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%. CONCLUSIONS Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; C1 [Sweeney, Christopher J.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sweeney, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. [Carducci, Michael; Eisenberger, Mario] Johns Hopkins Univ, Baltimore, MD USA. [Liu, Glenn; Jarrard, David F.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Jarrard, David F.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Wong, Yu-Ning] Temple Univ Hlth Syst, Fox Chase Canc Ctr, Philadelphia, PA USA. [Hahn, Noah] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Kohli, Manish] Mayo Clin, Rochester, MN USA. [Cooney, Matthew M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Garcia, Jorge A.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Dreicer, Robert] Univ Virginia, Ctr Canc, Charlottesville, VA 22908 USA. [Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Picus, Joel] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Shevrin, Daniel] NorthShore Univ HealthSystem, Evanston, IL USA. [Hussain, Maha] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [DiPaola, Robert S.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. RP Sweeney, CJ (reprint author), Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. EM christopher_sweeney@dfci.harvard.edu FU National Cancer Institute FX Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985. NR 26 TC 225 Z9 226 U1 11 U2 29 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 AUG 20 PY 2015 VL 373 IS 8 BP 737 EP 746 DI 10.1056/NEJMoa1503747 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CP2LU UT WOS:000359709400010 PM 26244877 ER PT J AU Kelley, AS Morrison, RS AF Kelley, Amy S. Morrison, R. Sean TI Palliative Care for the Seriously Ill SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; ADVANCED CANCER-PATIENTS; QUALITY-OF-LIFE; SPIRITUAL CARE; NEAR-DEATH; ADVANCED ILLNESS; MEDICAL-CARE; LAST WEEK; END; COMMUNICATION C1 [Kelley, Amy S.; Morrison, R. Sean] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Kelley, Amy S.; Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Kelley, AS (reprint author), Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM amy.kelley@mssm.edu FU NIA NIH HHS [K23 AG040774, K24 AG022345, P30 AG028741, R24 AG044300] NR 56 TC 45 Z9 46 U1 3 U2 10 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 AUG 20 PY 2015 VL 373 IS 8 BP 747 EP 755 DI 10.1056/NEJMra1404684 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CP2LU UT WOS:000359709400011 PM 26287850 ER PT J AU Klig, JE Madhavan, VL Rebello, GN Shailam, R AF Klig, Jean E. Madhavan, Vandana L. Rebello, Gleeson N. Shailam, Randheer TI Case 26-2015: A 9-Month-Old Girl with Recurrent Fevers SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SEPTIC ARTHRITIS; PROLONGED FEVER; UNKNOWN ORIGIN; CHILDREN; HIP; ALGORITHM; INFANCY; MODEL C1 [Klig, Jean E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Madhavan, Vandana L.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Rebello, Gleeson N.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. [Shailam, Randheer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Klig, Jean E.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Madhavan, Vandana L.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Rebello, Gleeson N.] Harvard Univ, Sch Med, Dept Orthopaed, Boston, MA USA. [Shailam, Randheer] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Klig, JE (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. FU Harvard Medical School Department of Continuing Education FX This case was presented at the postgraduate course "Primary Care Pediatrics," directed by Drs. John P. T. Co, Peter T. Greenspan, Ronni L. Goldsmith, Janice A. Lowe, and Ronald E. Kleinman and sponsored by the Harvard Medical School Department of Continuing Education. NR 20 TC 0 Z9 0 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 20 PY 2015 VL 373 IS 8 BP 757 EP 766 DI 10.1056/NEJMcpc1400843 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CP2LU UT WOS:000359709400013 PM 26287852 ER PT J AU Sartelli, M Malangoni, MA Abu-Zidan, FM Griffiths, EA Di Bella, S McFarland, LV Eltringham, I Shelat, VG Velmahos, GC Kelly, CP Khanna, S Abdelsattar, ZM Alrahmani, L Ansaloni, L Augustin, G Bala, M Barbut, F Ben-Ishay, O Bhangu, A Biffl, WL Brecher, SM Camacho-Ortiz, A Cainzos, MA Canterbury, LA Catena, F Chan, S Cherry-Bukowiec, JR Clanton, J Coccolini, F Cocuz, ME Coimbra, R Cook, CH Cui, YF Czepiel, J Das, K Demetrashvili, Z Di Carlo, I Di Saverio, S Dumitru, IM Eckert, C Eckmann, C Eiland, EH Enani, MA Faro, M Ferrada, P Forrester, JD Fraga, GP Frossard, JL Galeiras, R Ghnnam, W Gomes, CA Gorrepati, V Ahmed, MH Herzog, T Humphrey, F Kim, JI Isik, A Ivatury, R Lee, YY Juang, P Furuya-Kanamori, L Karamarkovic, A Kim, PK Kluger, Y Ko, WC LaBarbera, FD Lee, JG Leppaniemi, A Lohsiriwat, V Marwah, S Mazuski, JE Gokhan, M Moore, EE Moore, FA Nord, CE Ordonez, CA Pereira, GA Petrosillo, N Portela, F Puri, BK Ray, A Raza, M Rems, M Sakakushev, BE Sganga, G Spigaglia, P Stewart, DB Tattevin, P Timsit, JF To, KB Trana, C Uhl, W Urbanek, L van Goor, H Vassallo, A Zahar, JR Caproli, E Viale, P AF Sartelli, Massimo Malangoni, Mark A. Abu-Zidan, Fikri M. Griffiths, Ewen A. Di Bella, Stefano McFarland, Lynne V. Eltringham, Ian Shelat, Vishal G. Velmahos, George C. Kelly, Ciaran P. Khanna, Sahil Abdelsattar, Zaid M. Alrahmani, Layan Ansaloni, Luca Augustin, Goran Bala, Miklosh Barbut, Frederic Ben-Ishay, Offir Bhangu, Aneel Biffl, Walter L. Brecher, Stephen M. Camacho-Ortiz, Adrian Cainzos, Miguel A. Canterbury, Laura A. Catena, Fausto Chan, Shirley Cherry-Bukowiec, Jill R. Clanton, Jesse Coccolini, Federico Cocuz, Maria Elena Coimbra, Raul Cook, Charles H. Cui, Yunfeng Czepiel, Jacek Das, Koray Demetrashvili, Zaza Di Carlo, Isidoro Di Saverio, Salomone Dumitru, Irina Magdalena Eckert, Catherine Eckmann, Christian Eiland, Edward H. Enani, Mushira Abdulaziz Faro, Mario Ferrada, Paula Forrester, Joseph Derek Fraga, Gustavo P. Frossard, Jean Louis Galeiras, Rita Ghnnam, Wagih Gomes, Carlos Augusto Gorrepati, Venkata Ahmed, Mohamed Hassan Herzog, Torsten Humphrey, Felicia Kim, Jae Il Isik, Arda Ivatury, Rao Lee, Yeong Yeh Juang, Paul Furuya-Kanamori, Luis Karamarkovic, Aleksandar Kim, Peter K. Kluger, Yoram Ko, Wen Chien LaBarbera, Francis D. Lee, Jae Gil Leppaniemi, Ari Lohsiriwat, Varut Marwah, Sanjay Mazuski, John E. Metan, Gokhan Moore, Ernest E. Moore, Frederick Alan Nord, Carl Erik Ordonez, Carlos A. Pereira Junior, Gerson Alves Petrosillo, Nicola Portela, Francisco Puri, Basant K. Ray, Arnab Raza, Mansoor Rems, Miran Sakakushev, Boris E. Sganga, Gabriele Spigaglia, Patrizia Stewart, David B. Tattevin, Pierre Timsit, Jean Francois To, Kathleen B. Trana, Cristian Uhl, Waldemar Urbanek, Libor van Goor, Harry Vassallo, Angela Zahar, Jean Ralph Caproli, Emanuele Viale, Pierluigi TI WSES guidelines for management of Clostridium difficile infection in surgical patients SO WORLD JOURNAL OF EMERGENCY SURGERY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; FECAL MICROBIOTA TRANSPLANTATION; CLINICAL-PRACTICE GUIDELINES; PROTON PUMP INHIBITORS; LENGTH-OF-STAY; RISK-FACTORS; PSEUDOMEMBRANOUS COLITIS; TOXIN-B; HOSPITALIZED-PATIENTS; TREATMENT STRATEGIES AB In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients. C1 [Sartelli, Massimo] Macerata Hosp, Dept Surg, I-62019 Macerata, Italy. [Malangoni, Mark A.] Amer Board Surg, Philadelphia, PA USA. [Abu-Zidan, Fikri M.] UAE Univ, Coll Med & Hlth Sci, Dept Surg, Al Ain, U Arab Emirates. [Griffiths, Ewen A.] Queen Elizabeth Hosp, Dept Surg, Birmingham B15 2TH, W Midlands, England. [Di Bella, Stefano; Petrosillo, Nicola] Natl Inst Infect Dis L Spallanzani, Infect Dis Div 2, Rome, Italy. [McFarland, Lynne V.] Univ Washington, Sch Pharm, Dept Med Chem, Washington, DC USA. [Eltringham, Ian] Kings Coll Hosp London, Dept Med Microbiol, London, England. [Shelat, Vishal G.] Tan Tock Seng Hosp, Dept Surg, Singapore, Singapore. [Velmahos, George C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Surg & Surg Crit Care, Boston, MA USA. [Kelly, Ciaran P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Sch Med, Boston, MA 02215 USA. [Khanna, Sahil] Mayo Clin, Dept Med, Div Gastroenterol & Hepatol, Rochester, MN USA. [Abdelsattar, Zaid M.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Alrahmani, Layan] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Ansaloni, Luca; Coccolini, Federico] Papa Giovanni XXIII Hosp, Gen Surg 1, Bergamo, Italy. [Augustin, Goran] Univ Hosp Ctr Zagreb, Dept Surg, Zagreb, Croatia. [Augustin, Goran] Univ Zagreb, Sch Med, Zagreb 41001, Croatia. [Bala, Miklosh] Hadassah Hebrew Univ, Ctr Med, Trauma & Acute Care Surg Unit, Jerusalem, Israel. [Barbut, Frederic] Grp Hosp Est Parisien HUEP, UHLIN, Natl Reference Lab Clostridium Difficile, Paris, France. [Ben-Ishay, Offir; Kluger, Yoram] Rambam Hlth Care Campus, Dept Gen Surg, Haifa, Israel. [Bhangu, Aneel] Queen Elizabeth Hosp, Acad Dept Surg, Birmingham B15 2TH, W Midlands, England. [Biffl, Walter L.; Moore, Ernest E.] Univ Colorado, Dept Surg, Denver Hlth Med Ctr, Denver, CO 80202 USA. [Brecher, Stephen M.] VA Boston Healthcare Syst, Pathol & Lab Med, West Roxbury, MA USA. [Brecher, Stephen M.] BU Sch Med, Boston, MA USA. [Camacho-Ortiz, Adrian] Univ Hosp, Dept Internal Med, Monterrey, Mexico. [Cainzos, Miguel A.] Univ Santiago de Compostela, Dept Surg, Santiago De Compostela, Spain. [Canterbury, Laura A.] Univ Alberta, Dept Pathol, Edmonton, AB T6G 2E1, Canada. [Catena, Fausto] Maggiore Parma Hosp, Emergency Surg Dept, Parma, Italy. [Chan, Shirley] Medway Maritime Hosp, Dept Gen Surg, Gillingham Kent, England. [Cherry-Bukowiec, Jill R.; To, Kathleen B.] Univ Michigan, Dept Surg, Div Acute Care Surg, Ann Arbor, MI 48109 USA. [Clanton, Jesse] Northeast Ohio Med Univ, Dept Surg, Summa Akron City Hosp, Akron, OH USA. [Cocuz, Maria Elena] Transilvania Univ, Infect Dis Hosp, Fac Med, Brasov, Romania. [Coimbra, Raul] Univ Calif San Diego Hlth Sci, Div Trauma Surg Crit Care Burns & Acute Care, San Diego, CA USA. [Cook, Charles H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Acute Care Surg Trauma & Surg Crit Care, Dept Surg,Med Sch, Boston, MA 02215 USA. [Cui, Yunfeng] Tianjin Med Univ, Nankai Clin Sch Med, Nankai Hosp, Dept Surg, Tianjin, Peoples R China. [Czepiel, Jacek] Jagiellonian Univ, Coll Med, Dept Infect Dis, Krakow, Poland. [Das, Koray] Adana Numune Training & Res Hosp, Dept Gen Surg, Adana, Turkey. [Demetrashvili, Zaza] Tbilisi State Med Univ, Dept Surg, Kipshidze Cent Univ Hosp, Tbilisi, Rep of Georgia. [Di Carlo, Isidoro] Hamad Gen Hosp, Dept Surg, Doha, Qatar. [Di Saverio, Salomone] Maggiore Hosp, Trauma Surg Unit, Bologna, Italy. [Dumitru, Irina Magdalena] Ovidius Univ, Clin Infect Dis Hosp, Constanta, Romania. [Eckert, Catherine] St Antoine Hosp, AP HP, Natl Reference Lab Clostridium Difficile, Paris, France. [Eckmann, Christian] Hosp Med Univ Hannover, Klinikum Peine, Dept Gen Visceral & Thorac Surg, Peine, Germany. [Eiland, Edward H.] Vital Care Inc, Meridian, MS USA. [Enani, Mushira Abdulaziz] King Fahad Med City, Infect Dis Sect, Dept Med, Riyadh, Saudi Arabia. [Faro, Mario] ABC Med Sch, Dept Gen Surg, Trauma & Emergency Surg Div, Santo Andre, SP, Brazil. [Ferrada, Paula; Ivatury, Rao] Virginia Commonwealth Univ, Div Trauma Crit Care & Emergency Surg, Richmond, VA USA. [Forrester, Joseph Derek] Stanford Univ, Dept Surg, Stanford, CA 94305 USA. [Fraga, Gustavo P.] Univ Estadual Campinas, Div Trauma Surg, Hosp Clin, Sch Med Sci, Campinas, SP, Brazil. [Frossard, Jean Louis] Univ Hosp Geneva, Serv Gastroenterol & Hepatol, Geneva, Switzerland. [Galeiras, Rita] Univ Coruna UDC, Crit Care Unit, Inst Invest Biomed A Coruna INIBIC, CHUAC, La Coruna, Spain. [Ghnnam, Wagih] Mansoura Univ, Fac Med, Dept Surg Mansoura, Mansoura, Egypt. [Gomes, Carlos Augusto] Univ Fed Juiz de Fora, Dept Surg, Hosp Univ HU Terezinha Jesus, Fac Ciencias Med Saude Juiz de Fora SUPREMA, Juiz de Fora, Brazil. [Gorrepati, Venkata; LaBarbera, Francis D.] Pinnacle Hlth Hosp, Dept Internal Med, Harrisburg, PA USA. [Ahmed, Mohamed Hassan] Milton Keynes Univ Hosp NHS Fdn Trust, Dept Med, Milton Keynes, Bucks, England. [Herzog, Torsten; Uhl, Waldemar] Ruhr Univ Bochum, Dept Surg, St Josef Hosp, Bochum, Germany. [Humphrey, Felicia; Ray, Arnab] Ochsner Clin Fdn, Dept Gastroenterol & Hepatol, New Orleans, LA USA. [Kim, Jae Il] Inje Univ, Coll Med, Ilsan Paik Hosp, Dept Surg, Goyang, South Korea. [Isik, Arda] Erzincan Univ, Mengucek Gazi Training & Res Hosp, Dept Gen Surg, Erzincan, Turkey. [Lee, Yeong Yeh] Univ Sains Malaysia, Sch Med Sci, Kota Baharu, Kelantan, Malaysia. [Juang, Paul] St Louis Coll Pharm, Dept Pharm Practice, St Louis, MO USA. [Furuya-Kanamori, Luis] Australian Natl Univ, Res Sch Populat Hlth, Acton, ACT, Australia. [Karamarkovic, Aleksandar] Univ Belgrade, Univ Clin Ctr Serbia, Clin Emergency Surg, Fac Med, Belgrade, Serbia. [Kim, Peter K.] North Bronx Healthcare Network, Albert Einstein Coll Med, Gen & Trauma Surg, Bronx, NY USA. [Ko, Wen Chien] Natl Cheng Kung Univ Hosp, Div Infect Dis, Dept Internal Med, Tainan 70428, Taiwan. [Lee, Jae Gil] Yonsei Univ, Coll Med, Dept Surg, Div Crit Care & Trauma Surg, Seoul, South Korea. [Leppaniemi, Ari] Helsinki Univ Hosp Meilahti, Abdominal Ctr, Helsinki, Finland. [Lohsiriwat, Varut] Mahidol Univ, Dept Surg, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand. [Marwah, Sanjay] Post Grad Inst Med Sci, Dept Surg, Rohtak, Haryana, India. [Mazuski, John E.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Metan, Gokhan] Hacettepe Univ, Fac Med, Dept Infect Dis & Clin Microbiol, TR-06100 Ankara, Turkey. [Moore, Frederick Alan] Univ Florida, Dept Surg, Gainesville, FL USA. [Nord, Carl Erik] Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Stockholm, Sweden. [Ordonez, Carlos A.] Univ Valle, Hosp Univ Valle, Dept Surg, Fdn Valle Lili, Cali, Colombia. [Pereira Junior, Gerson Alves] Dept Surg, Emergency Surg & Trauma Unit, Ribeirao Preto, Brazil. [Portela, Francisco] Ctr Hosp & Univ Coimbra, Dept Gastroenterol, Coimbra, Portugal. [Puri, Basant K.] Hammersmith Hosp, Dept Med, London W12 0HS, England. [Puri, Basant K.] Univ London Imperial Coll Sci Technol & Med, London, England. [Raza, Mansoor] Milton Keynes Univ Hosp NHS Fdn Trust, Infect Dis & Microbiol Unit, Milton Keynes, Bucks, England. [Rems, Miran] Gen Hosp Jesenice, Dept Abdominal & Gen Surg, Jesenice, Slovenia. [Sakakushev, Boris E.] Med Univ Plovdiv, Dept Surg, Plovdiv, Bulgaria. [Sganga, Gabriele] Univ Cattolica Sacro Cuore, Dept Surg, Div Gen Surg & Organ Transplantat, I-00168 Rome, Italy. [Spigaglia, Patrizia] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy. [Stewart, David B.] Penn State Univ, Coll Med, Dept Surg, Hershey, PA USA. [Tattevin, Pierre] Pontchaillou Univ Hosp, Infect Dis & Intens Care Unit, Rennes, France. [Timsit, Jean Francois] Med & Infect Dis ICU, Bichat Hosp, AP HP, Paris, France. [Trana, Cristian] Macerata Hosp, Emergency Med & Surg, Macerata, Italy. [Urbanek, Libor] Univ Hosp St Ann Brno, Surg Clin 1, Brno, Czech Republic. [van Goor, Harry] Radboud Univ Nijmegen, Dept Surg, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Vassallo, Angela] Providence St Johns Hlth Ctr, Infect Prevent Epidemiol, Santa Monica, CA USA. [Zahar, Jean Ralph] CHU Angers, Univ Angers, Infect Control Unit, Angers, France. [Caproli, Emanuele] Ancona Univ Hosp, Dept Surg, Ancona, Italy. [Viale, Pierluigi] St Orsola Malpighi Univ Hosp, Clin Infect Dis, Bologna, Italy. RP Sartelli, M (reprint author), Macerata Hosp, Dept Surg, Via Santa Lucia 2, I-62019 Macerata, Italy. EM m.sartelli@virgilio.it RI Goor, H./H-8035-2014; Di Bella, Stefano/K-8162-2016; ghannam, wagih/I-5212-2013; OI Di Bella, Stefano/0000-0001-6121-7009; Galeiras, Rita/0000-0002-8551-3731; Griffiths, Ewen/0000-0001-6630-3547; Sakakushev, Boris/0000-0001-8399-0115; petrosillo, nicola/0000-0002-2585-7567; ghannam, wagih/0000-0003-3599-9929; Augustin, Goran/0000-0002-0202-3324 FU AHRQ HHS [T32 HS000053] NR 225 TC 9 Z9 10 U1 6 U2 26 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-7922 J9 WORLD J EMERG SURG JI World J. Emerg. Surg. PD AUG 20 PY 2015 VL 10 AR 38 DI 10.1186/s13017-015-0033-6 PG 23 WC Emergency Medicine; Surgery SC Emergency Medicine; Surgery GA CP2EB UT WOS:000359689200001 PM 26300956 ER PT J AU Lee, SH Coutu, JP Wilkens, P Yendiki, A Rosas, HD Salat, DH AF Lee, S. -H. Coutu, J. -P. Wilkens, P. Yendiki, A. Rosas, H. D. Salat, D. H. CA ADNI TI TRACT-BASED ANALYSIS OF WHITE MATTER DEGENERATION IN ALZHEIMER'S DISEASE SO NEUROSCIENCE LA English DT Article DE Alzheimer's disease; mild cognitive impairment; white matter; hippocampus; cingulum and angular bundle ID HUMAN CEREBRAL-CORTEX; LONGITUDINAL NEUROIMAGE DATA; MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; AUTOMATED SEGMENTATION; HIPPOCAMPAL VOLUME; DIFFUSION; BRAIN; MRI; INTEGRITY AB Although much prior work has focused on the known cortical pathology that defines Alzheimer's disease (AD) histologically, recent work has additionally demonstrated substantial damage to the cerebral white matter in this condition. While there is large evidence of diffuse damage to the white matter in AD, it is unclear whether specific white matter tracts exhibit a more accelerated pattern of damage and whether the damage is associated with the classical neurodegenerative changes of AD. In this study, we investigated microstructural differences in the large fascicular bundles of the cerebral white matter of individuals with AD and mild cognitive impairment (MCI), using recently developed automated diffusion tractography procedures in the Alzheimer's disease Neuroimaging Initiative (ADNI) dataset. Eighteen major fiber bundles in a total of 36 individuals with AD, 81 MCI and 60 control participants were examined with the TRActs Constrained by UnderLying Anatomy (TRACULA) procedure available as part of the FreeSurfer image processing software package. For each fiber bundle, the mean fractional anisotropy (FA), and mean, radial and axial diffusivities were calculated. Individuals with AD had increased diffusivities in both left and right cingulum-angular bundles compared to control participants (p < 0.001). Individuals with MCI also had increased axial and mean diffusivities and increased FA in both cingulum-angular bundles compared to control participants (p < 0.05) and decreased radial diffusivity compared to individuals with AD (p < 0.05). We additionally examined how white matter deterioration relates to hippocampal volume, a traditional imaging measure of AD pathology, and found the strongest negative correlations in AD patients between hippocampal volume and the diffusivities of the cingulum-angular and cingulum-cingulate gyrus bundles and of the corticospinal tracts (p < 0.05). However, statistically controlling for hippocampal volume did not remove all group differences in white matter measures, suggesting a unique contribution of white matter damage to AD unexplained by this disease biomarker. These results suggest that (1) AD-associated deterioration of white matter fibers is greatest in tracts known to be connected to areas of pathology in AD and (2) lower white matter tract integrity is more diffusely associated with lower hippocampal volume indicating that the pathology in the white matter follows to some degree the neurodegenerative staging and progression of this condition. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Lee, S. -H.; Coutu, J. -P.; Wilkens, P.; Yendiki, A.; Rosas, H. D.; Salat, D. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Lee, S. -H.] Kangwon Natl Univ, Sch Med, Dept Neurol, Chuncheon Si 200701, Gangwon Do, South Korea. [Coutu, J. -P.] MIT, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Cambridge, MA 02139 USA. [Wilkens, P.; Rosas, H. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Yendiki, A.; Salat, D. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Salat, D. H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. RP Lee, SH (reprint author), Kangwon Natl Univ, Sch Med, Dept Neurol, 1 Kangwondaehak Gil, Chuncheon Si 200701, Gangwon Do, South Korea. EM movement@kangwon.ac.kr OI /0000-0003-4895-5642 FU National Institutes of Health [R01NR010827, NS042861, NS058793]; Center for Functional Neuroimaging Technologies [P41RR14075]; Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health; NCRR [S10RR021110, S10RR023401, S10RR019307, S10RR019254, S10RR023043]; Kangwon National University; Kangwon National University Hospital; Fonds Quebecois de la Recherche-Sante; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd; Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; Takeda Pharmaceutical Company FX This study was funded by the National Institutes of Health grant R01NR010827, and was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the National Institutes of Health grants R01NR010827, NS042861, NS058793 and by the Center for Functional Neuroimaging Technologies, 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 and/or High-End Instrumentation Grant Program; specifically, grant numbers S10RR021110, S10RR023401, S10RR019307, S10RR019254 and S10RR023043. Seung-Hwan Lee was funded by the Kangwon National University and Kangwon National University Hospital. Jean-Philippe Coutu was funded by the Fonds Quebecois de la Recherche-Sante.; Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. NR 80 TC 8 Z9 9 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD AUG 20 PY 2015 VL 301 BP 79 EP 89 DI 10.1016/j.neuroscience.2015.05.049 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CM7MO UT WOS:000357877800008 PM 26026680 ER PT J AU Scremin, OU Roch, M Norman, KM Djazayeri, S Liu, YY AF Scremin, O. U. Roch, M. Norman, K. M. Djazayeri, S. Liu, Y. -Y. TI BRAIN ACETYLCHOLINE AND CHOLINE CONCENTRATIONS AND DYNAMICS IN A MURINE MODEL OF THE FRAGILE X SYNDROME: AGE, SEX AND REGION-SPECIFIC CHANGES SO NEUROSCIENCE LA English DT Article DE acetylcholine turnover; mice; cholinergic function; GCMS; fmr1-KO mice ID FMR1 KNOCKOUT MICE; MAGNETIC-RESONANCE-SPECTROSCOPY; GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; WORKING MEMORY; CGG REPEAT; LONG-TERM; NEURONS; EXPRESSION; SYSTEMS AB Fragile X syndrome is a learning disability caused by excess of CGG repeats in the 50 untranslated region of the Fragile X gene (FMR1) silencing its transcription and translation. We used a murine model of this condition, Fmr1 knock-out mice (KO) to study acetylcholine (ACh) metabolism and compared it to that of wild-type control mice (WT). Brain endogenous ACh (D0ACh), free choline (D0Ch), their deuterated variants D4ACh and D4Ch and mole ratios (AChMR and ChMR) were measured by gas chromatography- mass spectrometry in the cerebral hemisphere, cerebral cortex, hippocampus and cerebellum, following D4Ch administration. Regression analysis indicated a significant decrease with age (negative slope) of D4ACh, AChMR, D4Ch and ChMR in WT mice. Age dependence was only present for D4ACh and AChMR in KO mice. Analysis of variance with age as covariate indicated a significant greater D4Ch in the cerebral cortex of KO females when compared to WT females. Contrasts between sexes within genotypes indicated lower D0Ch in cortex and cerebellum of female KO mice but not in WT and lower D4Ch in hippocampus of female KO and WT mice. In conclusion, after adjusting for age, D0ACh concentrations and synthesis from deuterium-labeled Ch were similar in KO and control WT mice in all brain regions. In contrast, significant changes in Ch dynamics were found in hippocampus and cerebral cortex of KO mice that might contribute to the pathogenesis of FXS. Published by Elsevier Ltd. C1 [Scremin, O. U.; Roch, M.; Norman, K. M.; Djazayeri, S.; Liu, Y. -Y.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. [Scremin, O. U.] Univ Calif Los Angeles, Dept Physiol, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Liu, Y. -Y.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Scremin, OU (reprint author), Greater Los Angeles VA Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM oscremin@ucla.edu FU VA RR&D Senior Research Career Scientist Award FX This work was supported by a VA RR&D Senior Research Career Scientist Award to O.U. Scremin. NR 62 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 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD AUG 20 PY 2015 VL 301 BP 520 EP 528 DI 10.1016/j.neuroscience.2015.06.036 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CM7MO UT WOS:000357877800045 PM 26117713 ER PT J AU Rellan-Alvarez, R Lobet, G Lindner, H Pradier, PL Sebastian, J Yee, MC Geng, Y Trontin, C LaRue, T Schrager-Lavelle, A Haney, CH Nieu, R Maloof, J Vogel, JP Dinneny, JR AF Rellan-Alvarez, Ruben Lobet, Guillaume Lindner, Heike Pradier, Pierre-Luc Sebastian, Jose Yee, Muh-Ching Geng, Yu Trontin, Charlotte LaRue, Therese Schrager-Lavelle, Amanda Haney, Cara H. Nieu, Rita Maloof, Julin Vogel, John P. Dinneny, Jose R. TI GLO-Roots: an imaging platform enabling multidimensional characterization of soil-grown root systems SO ELIFE LA English DT Article ID BOX PROTEIN TIR1; ARABIDOPSIS SEEDLINGS; AUXIN RECEPTOR; ARCHITECTURE; BRACHYPODIUM; REPORTER; SHAPE; PHOTOMORPHOGENESIS; EXPRESSION; MECHANISM AB Root systems develop different root types that individually sense cues from their local environment and integrate this information with systemic signals. This complex multi-dimensional amalgam of inputs enables continuous adjustment of root growth rates, direction, and metabolic activity that define a dynamic physical network. Current methods for analyzing root biology balance physiological relevance with imaging capability. To bridge this divide, we developed an integrated-imaging system called Growth and Luminescence Observatory for Roots (GLO-Roots) that uses luminescence-based reporters to enable studies of root architecture and gene expression patterns in soil-grown, light-shielded roots. We have developed image analysis algorithms that allow the spatial integration of soil properties, gene expression, and root system architecture traits. We propose GLO-Roots as a system that has great utility in presenting environmental stimuli to roots in ways that evoke natural adaptive responses and in providing tools for studying the multi-dimensional nature of such processes. C1 [Rellan-Alvarez, Ruben; Lindner, Heike; Pradier, Pierre-Luc; Sebastian, Jose; Yee, Muh-Ching; Geng, Yu; Trontin, Charlotte; Dinneny, Jose R.] Carnegie Inst Sci, Dept Plant Biol, 290 Panama St, Stanford, CA 94305 USA. [Lobet, Guillaume] Univ Liege, PhytoSyst, Liege, Belgium. [Geng, Yu; Vogel, John P.] US DOE, Joint Genome Inst, Walnut Creek, PA USA. [LaRue, Therese] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Schrager-Lavelle, Amanda; Maloof, Julin] Univ Calif Davis, Dept Plant Biol, Davis, CA 95616 USA. [Haney, Cara H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol, Boston, MA USA. [Nieu, Rita] USDA, Western Reg Res Ctr, Albany, CA USA. RP Dinneny, JR (reprint author), Carnegie Inst Sci, Dept Plant Biol, 290 Panama St, Stanford, CA 94305 USA. EM jdinneny@carnegiescience.edu OI Yee, Muh-ching/0000-0002-0445-7927; Sebastian, Jose/0000-0002-1826-0308; Vogel, John/0000-0003-1786-2689; Rellan-Alvarez, Ruben/0000-0001-6843-3716 FU National Science Foundation [MCB-115795, MCB-0519898, IOS-0820854]; U.S. Department of Energy [DE-SC0008769, DE-AI02-07ER64452]; National Institutes of Health [GM48707]; Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research); Consejo Nacional de Ciencia y Tecnologia (National Council of Science and Technology, Mexico) [CB-2014-01-238101] FX National Science Foundation MCB-115795 Jose R Dinneny; U.S. Department of Energy DE-SC0008769 Jose R Dinneny; National Science Foundation MCB-0519898 Cara H Haney; National Science Foundation IOS-0820854 Amanda Schrager-Lavelle, Julin Maloof; National Institutes of Health GM48707 Cara H Haney; Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research) Guillaume Lobet; Consejo Nacional de Ciencia y Tecnologia (National Council of Science and Technology, Mexico) CB-2014-01-238101 Ruben Rellan-Alvarez; U.S. Department of Energy DE-AI02-07ER64452 John P Vogel; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. NR 58 TC 15 Z9 15 U1 7 U2 18 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD AUG 19 PY 2015 VL 4 AR e07597 DI 10.7554/eLife.07597 PG 26 WC Biology SC Life Sciences & Biomedicine - Other Topics GA DI9HU UT WOS:000373814300001 ER PT J AU Goldman, AW Burmeister, Y Cesnulevicius, K Herbert, M Kane, M Lescheid, D McCaffrey, T Schultz, M Seilheimer, B Smit, A St Laurent, G Berman, B AF Goldman, Alyssa W. Burmeister, Yvonne Cesnulevicius, Konstantin Herbert, Martha Kane, Mary Lescheid, David McCaffrey, Timothy Schultz, Myron Seilheimer, Bernd Smit, Alta St Laurent, Georges, III Berman, Brian TI Bioregulatory systems medicine: an innovative approach to integrating the science of molecular networks, inflammation, and systems biology with the patient's autoregulatory capacity? SO FRONTIERS IN PHYSIOLOGY LA English DT Article DE bioregulatory systems medicine; systems biology; autoregulation; inflammation; systems medicine; genomics ID IMMUNOLOGICAL SYNAPSE; COST-EFFECTIVENESS; LIPID MEDIATORS; HUMAN-DISEASES; CANCER; RESOLUTION; BIOMARKER; STRESS; VIEW; HOMEOSTASIS AB Bioregulatory systems medicine (BrSM) is a paradigm that aims to advance current medical practices. The basic scientific and clinical tenets of this approach embrace an interconnected picture of human health, supported largely by recent advances in systems biology and genomics, and focus on the implications of multi-scale interconnectivity for improving therapeutic approaches to disease. This article introduces the formal incorporation of these scientific and clinical elements into a cohesive theoretical model of the BrSM approach. The authors review this integrated body of knowledge and discuss how the emergent conceptual model offers the medical field a new avenue for extending the armamentarium of current treatment and healthcare, with the ultimate goal of improving population health. C1 [Goldman, Alyssa W.; Kane, Mary] Concept Syst Inc, Ithaca, NY USA. [Goldman, Alyssa W.] Cornell Univ, Dept Sociol, Ithaca, NY 14853 USA. [Burmeister, Yvonne; Cesnulevicius, Konstantin; Schultz, Myron; Seilheimer, Bernd; Smit, Alta] Biol Heilmittel Heel GmbH, D-76532 Baden Baden, Germany. [Herbert, Martha] Massachusetts Gen Hosp, Transcend Res Lab, Boston, MA 02114 USA. [Lescheid, David] Int Acad Bioregulatory Med, Baden Baden, Germany. [McCaffrey, Timothy] George Washington Univ, Med Ctr, Div Genom Med, Washington, DC 20037 USA. [St Laurent, Georges, III] St Laurent Inst, Vancouver, WA USA. [Berman, Brian] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. RP Cesnulevicius, K (reprint author), Biol Heilmittel Heel GmbH, Med Affairs & Res, Dr Reckeweg Str 2-4, D-76532 Baden Baden, Germany. EM konstantin.cesnulevicius@heel.com FU Biologische Heilmittel Heel GmbH FX The authors are grateful to the scientific and clinical experts who participated in various stages of the model development process. The authors thank Mark Mazaitis for his work on the figures in this article. The initiative management, organization of the international Think Tanks, and medical writing services from Concept Systems, Inc. were funded by Biologische Heilmittel Heel GmbH. NR 110 TC 0 Z9 0 U1 5 U2 8 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PD AUG 19 PY 2015 VL 6 AR 225 DI 10.3389/fphys.2015.00225 PG 17 WC Physiology SC Physiology GA CQ3AS UT WOS:000360474500001 PM 26347656 ER PT J AU Matlis, S Boric, K Chu, CJ Kramer, MA AF Matlis, Sean Boric, Katica Chu, Catherine J. Kramer, Mark A. TI Robust disruptions in electroencephalogram cortical oscillations and large-scale functional networks in autism (vol 15, 97, 2015) SO BMC NEUROLOGY LA English DT Correction C1 [Matlis, Sean] Boston Univ, Grad Program Neurosci, Boston, MA 02215 USA. [Boric, Katica; Chu, Catherine J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Boric, Katica; Chu, Catherine J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kramer, Mark A.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Kramer, MA (reprint author), Boston Univ, Dept Math & Stat, 111 Cummington Mall, Boston, MA 02215 USA. EM mak@math.bu.edu NR 1 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 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD AUG 19 PY 2015 VL 15 AR 142 DI 10.1186/s12883-015-0391-4 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA CP2EK UT WOS:000359690100003 PM 26286517 ER PT J AU Habib, SL Mohan, S Liang, ST Li, BJ Yadav, M AF Habib, Samy L. Mohan, Sumathy Liang, Sitai Li, Baojie Yadav, Mukesh TI Novel mechanism of transcriptional regulation of cell matrix protein through CREB SO CELL CYCLE LA English DT Article DE AMPK; cell matrix; CREB; fibronectin; renal cells; transcription ID HUMAN TUBULOINTERSTITIAL CELLS; OXIDATIVE DNA-DAMAGE; COLLAGEN-SYNTHESIS; MAMMALIAN TARGET; PROXIMAL TUBULE; GROWTH; RAPAMYCIN; MTOR; FIBRONECTIN; EXPRESSION AB The transcription mechanism(s) of renal cell matrix accumulation in diabetes does not explored. Phosphorylation of the transcription factor cAMP-responsive element binding protein (CREB) significantly increased in cells treated with high glucose (HG) compared to cell grown in normal glucose (NG). Cells pretreated with rapamycin before exposure to HG showed significant decrease phosphorylation of CREB, increase in AMPK activity and decrease protein/mRNA and promoter activity of fibronectin. In addition, cells transfected with siRNA against CREB showed significant increase in AMPK activity, decrease in protein/mRNA and promoter activity of fibronectin. Cells treated with HG showed nuclear localization of p-CREB while pretreated cells with rapamycin reversed HG effect. Moreover, gel shift analysis shows increase binding of CREB to fibronectin promoter in cells treated with HG while cells pretreated with rapamycin reversed the effect of HG. Furthermore, db/db mice treated with rapamycin showed significant increase in AMPK activity, decrease in expression of p-CREB and protein/mRNA of fibronectin. Strong staining of fibronectin and p-CREB was detected in kidney cortex of db/db mice while treated mice with rapamycin reversed hyperglycemia effect. In summary, our data provide a novel mechanism of transcriptional regulation of fibronectin through CREB that may be used as therapeutic approach to prevent diabetes complications. C1 [Habib, Samy L.] South Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. [Li, Baojie] Shanghai Jiao Tong Univ, Minist Educ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai 200030, Peoples R China. [Habib, Samy L.; Liang, Sitai; Yadav, Mukesh] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Mohan, Sumathy] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. RP Habib, SL (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. EM habib@uthscsa.edu FU American Heart Association; South Texas Veterans Healthcare System FX This work was supported in part by grants from the American Heart Association and Merit Review Award from South Texas Veterans Healthcare System (to SLH). NR 28 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD AUG 18 PY 2015 VL 14 IS 16 BP 2598 EP 2608 DI 10.1080/15384101.2015.1064204 PG 11 WC Cell Biology SC Cell Biology GA CQ0OG UT WOS:000360295400019 PM 26115221 ER PT J AU Jiang, YH Fan, X Yu, ZY Cheng, CJ Wang, XS Lo, EH Sun, XC Wang, XY AF Jiang, Yinghua Fan, Xiang Yu, Zhanyang Cheng, Chongjie Wang, Xiao-Shu Lo, Eng H. Sun, Xiaochuan Wang, Xiaoying TI Low dose tPA plus annexin A2 combination attenuates tPA delayed treatment-associated hemorrhage and improves recovery in rat embolic focal stroke SO NEUROSCIENCE LETTERS LA English DT Article DE Annexin A2; Tissue plasminogen activator; Embolic focal stroke; Combination thrombolytic therapy; Intracerebral hemorrhagic transformation; Long term neurological outcomes ID TISSUE-PLASMINOGEN ACTIVATOR; ISCHEMIC-STROKE; INTRACEREBRAL HEMORRHAGE; THERAPY; BRAIN; CELLS; IRON; THROMBOLYSIS; REPERFUSION; MECHANISMS AB We previously have shown that tissue type plasminogen activator (tPA) in combination with its receptor annexin A2 (rA2) protein significantly improved tPA thrombolytic efficacy. In this study we aimed to examine the therapeutic effects of the combination when treated at delayed 4-hour window after stroke compared to standard conventional tPA alone in an embolic focal stroke rat model. We compared effects of intravenous tPA alone (10 mg/kg) versus a combination of low-dose tPA (5 mg/kg) plus 10 mg/kg rA2. Totally 152 rats were used. Our results showed that: (1) at 24 h after stroke, the combination slightly reduced brain infarction compared to saline (9.2% reduction), and tPA (7.4% reduction), although the reductions did not reach statistical significance; while the combination significantly reduced (22.2% reduction) the conventional tPA-elevated intracerebral hemorrhagic (ICH) transformation; (2) at 7 days after stroke, the combination significantly attenuated conventional tPA alone-elevated iron deposition at pen-lesion area (68.2% reduction); (3) at 28 days after stroke, the combination significantly improved performance of adhesive tape-removal test, which was accompanied by a significantly higher micro vessel density at pen- infarct areas compared to conventional tPA alone group. In conclusion, compared to conventional tPA alone, when treated at delayed 4-hour after stroke, the combination of low-dose tPA plus rA2 therapy provides a safer profile by lowering risk of ICH transformation and improves neurological function recovery after stroke. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Jiang, Yinghua; Cheng, Chongjie; Wang, Xiao-Shu; Sun, Xiaochuan; Wang, Xiaoying] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Chongqing, Peoples R China. [Fan, Xiang] Tianjin Univ Tradit Chinese Med, Res Inst Tradit Chinese Med, Tianjin, Peoples R China. [Jiang, Yinghua; Fan, Xiang; Yu, Zhanyang; Cheng, Chongjie; Wang, Xiao-Shu; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02115 USA. [Jiang, Yinghua; Fan, Xiang; Yu, Zhanyang; Cheng, Chongjie; Wang, Xiao-Shu; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med,Neurosci Program, Boston, MA USA. RP Sun, XC (reprint author), Chongqing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Chongqing, Peoples R China. EM wangxi@helix.mgh.harvard.edu FU National Institute of Health [R01-NS065998, U01-NS072324] FX This work was supported in part by the National Institute of Health grants R01-NS065998 and U01-NS072324 (to X.W.). NR 24 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 18 PY 2015 VL 602 BP 73 EP 78 DI 10.1016/j.neulet.2015.06.050 PG 6 WC Neurosciences SC Neurosciences & Neurology GA CQ4TB UT WOS:000360596400014 PM 26149229 ER PT J AU Onofrey, S Aneja, J Haney, GA Nagami, EH DeMaria, A Lauer, GM Hills-Evans, K Barton, K Kulaga, S Bowen, MJ Cocoros, N McGovern, BH Church, DR Kim, AY AF Onofrey, Shauna Aneja, Jasneet Haney, Gillian A. Nagami, Ellen H. DeMaria, Alfred, Jr. Lauer, Georg M. Hills-Evans, Kelsey Barton, Kerri Kulaga, Stephanie Bowen, Melinda J. Cocoros, Noelle McGovern, Barbara H. Church, Daniel R. Kim, Arthur Y. TI Underascertainment of Acute Hepatitis C Virus Infections in the US Surveillance System SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID ACUTE VIRAL-HEPATITIS; INJECTION-DRUG USERS; UNITED-STATES; YOUNG-ADULTS; MASSACHUSETTS; EPIDEMIOLOGY; DIAGNOSIS; RISK AB Background: In 2010, the incidence of hepatitis C virus (HCV) infection in the United States was estimated to be 17 000 cases annually, based on 850 acute HCV cases reported to the Centers for Disease Control and Prevention by local public health authorities. Absence of symptomatic disease and lack of a specific laboratory test for acute infection complicates diagnosis and surveillance. Objective: To validate estimates of the incidence of acute HCV infection by determining the reporting rate of clinical diagnoses of acute infection to the Massachusetts Department of Public Health (MDPH) and Centers for Disease Control and Prevention. Design: Case series and chart review. Setting: Two hospitals and the state correctional health care system in Massachusetts. Patients: 183 patients clinically diagnosed with acute HCV infection from 2001 to 2011 and participating in a research study. Measurements: Rate of electronic case reporting of acute HCV infection to the MDPH and rate of subsequent confirmation according to national case definitions. Results: 149 of 183 (81.4%) clinical cases of acute HCV infection were reported to the MDPH for surveillance classification. The MDPH investigated 43 of these reports as potential acute cases of HCV infection based on their surveillance requirements; ultimately, only 1 met the national case definition and was counted in nationwide statistics published by the Centers for Disease Control and Prevention. Discordance in clinical and surveillance classification was often related to missing clinical or laboratory data at the MDPH as well as restrictive definitions, including requirements for negative hepatitis A and B laboratory results. Limitation: Findings may not apply to other jurisdictions because of differences in resources for surveillance. Conclusion: Clinical diagnoses of acute HCV infection were grossly underascertained by formal surveillance reporting. Incomplete clinician reporting, problematic case definitions, limitations of diagnostic testing, and imperfect data capture remain major limitations to accurate case ascertainment despite automated electronic laboratory reporting. These findings may have implications for national estimates of the incidence of HCV infection. C1 [Onofrey, Shauna; Haney, Gillian A.; Barton, Kerri; Church, Daniel R.] Massachusetts Dept Publ Hlth, Jamaica Plain, MA 02130 USA. [Aneja, Jasneet; Kulaga, Stephanie; Kim, Arthur Y.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Nagami, Ellen H.; McGovern, Barbara H.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [DeMaria, Alfred, Jr.] Massachusetts Dept Publ Hlth, Bur Infect Dis, William A Hinton State Lab Inst, Jamaica Plain, MA 02130 USA. [Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hills-Evans, Kelsey] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Bowen, Melinda J.] Massachusetts Partnership Correct Hlth Care, Westborough, MA 01581 USA. [Cocoros, Noelle] Harvard Univ, Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA 02215 USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kim, AY (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM shauna.onofrey@state.ma.us; akim1@mgh.harvard.edu FU National Institutes of Health. FX National Institutes of Health. NR 33 TC 8 Z9 8 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 18 PY 2015 VL 163 IS 4 BP 254 EP + DI 10.7326/M14-2939 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CQ0LC UT WOS:000360286400003 PM 26121304 ER PT J AU Downs, JR O'Malley, PG AF Downs, John R. O'Malley, Patrick G. TI Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2014 US Department of Veterans Affairs and US Department of Defense Clinical Practice Guideline SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID INTENSIVE STATIN THERAPY; CORONARY-HEART-DISEASE; 14 RANDOMIZED-TRIALS; C-REACTIVE PROTEIN; PRIMARY PREVENTION; CHOLESTEROL LEVELS; METAANALYSIS; EFFICACY; EVENTS; SAFETY AB Description: In December 2014, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the management of dyslipidemia for cardiovascular disease risk reduction in adults. This synopsis summarizes the major recommendations. Methods: On 30 September 2013, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, developed a simple 1-page algorithm, and rated each of 26 recommendations by using the Grading of Recommendations Assessment, Development, and Evaluation system. Recommendations: This synopsis summarizes key features of the guideline in 5 areas: elimination of treatment targets, additional tests for risk prediction, primary and secondary prevention, and laboratory testing. C1 [Downs, John R.] South Texas Vet Hlth Care Syst, Med Serv 111, San Antonio, TX 78229 USA. [O'Malley, Patrick G.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. RP Downs, JR (reprint author), South Texas Vet Hlth Care Syst, Med Serv 111, 7400 Merton Minter, San Antonio, TX 78229 USA. EM john.downs@va.gov NR 40 TC 17 Z9 18 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 18 PY 2015 VL 163 IS 4 BP 291 EP + DI 10.7326/M15-0840 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CQ0LC UT WOS:000360286400007 PM 26099117 ER PT J AU Lee, WC Catalano, PJ Yoo, JY Park, CJ Koutrakis, P AF Lee, Wan-Chen Catalano, Paul J. Yoo, Jun Young Park, Chan Jung Koutrakis, Petros TI Validation and Application of the Mass Balance Model To Determine the Effectiveness of Portable Air Purifiers in Removing Ultrafine and Submicrometer Particles in an Apartment SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID INDOOR AIR; DEPOSITION RATES; FINE PARTICLES; OUTDOOR ORIGIN; CLEANERS; TECHNOLOGIES; PERFORMANCE; POLLUTION; MORTALITY; FILTERS AB We validated the use of the mass balance model to determine the effectiveness of portable air purifiers in removing ultrafine (<0.10 mu m) and submicrometer particles (0.10-0.53 mu m) in an apartment. We evaluated two identical portable air purifiers, equipped with high efficiency particulate air filters, for their performance under three different air flow settings and three target air exchange rates: 0.60, 0.90, and 1.20 h(-1). We subsequently used a mixed effects model to estimate the slope between the measured and modeled effectiveness by particle size. Our study showed that effectiveness was highly particle size-dependent. For example, at the lowest target air exchange rate, it ranged from 0.33 to 0.56, 0.51 to 0.75, and 0.60 to 0.81 for the three air purifier flow settings, respectively. Our findings suggested that filtration was the dominant removal mechanism for submicrometer particles, whereas deposition could play a more important role in ultrafine particle removal. We found reasonable agreement between measured and modeled effectiveness with size-resolved slopes ranging from 1.11 +/- 0.06 to 1.25 +/- 0.07 (mean +/- SE), except for particles <35 nm. Our study design can be applied to investigate the performances of other portable air purifiers as well as the influences of various parameters on effectiveness in different residential settings. C1 [Lee, Wan-Chen; Koutrakis, Petros] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Catalano, Paul J.] Harvard Univ, TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Yoo, Jun Young; Park, Chan Jung] Seoul Natl Univ, Coway R&D Ctr, Seoul 151919, South Korea. RP Lee, WC (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, 401 Pk Dr,Landmark Ctr West, Boston, MA 02215 USA. EM wal954@mail.harvard.edu OI Lee, Wanchen/0000-0003-0853-8561 FU Coway Co., Ltd.; Taiwan Ministry of Education FX We thank Jack M. Wolfson for providing valuable insights and technical assistance in experimental procedures. We also express our gratitude to Stephen T. Ferguson for the generous help with setting up the air purifier testing system. This study was funded by Coway Co., Ltd. Wan-Chen Lee was supported by the Graduate Fellowship from the Taiwan Ministry of Education. NR 30 TC 0 Z9 0 U1 4 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X EI 1520-5851 J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD AUG 18 PY 2015 VL 49 IS 16 BP 9592 EP 9599 DI 10.1021/acs.est.5b03126 PG 8 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA CP4ZS UT WOS:000359891700025 PM 26207386 ER PT J AU Rigotti, NA AF Rigotti, Nancy A. TI e-Cigarette Use and Subsequent Tobacco Use by Adolescents New Evidence About a Potential Risk of e-Cigarettes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID ELECTRONIC CIGARETTES; ADULTS C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Internal Med, Dept Med, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St, Boston, MA 02114 USA. EM nrigotti@partners.org NR 17 TC 7 Z9 7 U1 0 U2 18 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 AUG 18 PY 2015 VL 314 IS 7 BP 673 EP 674 DI 10.1001/jama.2015.8382 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CP6SS UT WOS:000360019100014 PM 26284717 ER PT J AU Ruff, CT AF Ruff, Christian T. TI The Challenge of Getting it Just Right Optimizing Long-Term Antithrombotic Therapy After Acute Coronary Syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE acute coronary syndrome; anticoagulants; aspirin; factor Xa inhibitors; platelet aggregation inhibitors; secondary prevention ID ASSOCIATION TASK-FORCE; MYOCARDIAL-INFARCTION; ORAL ANTICOAGULANTS; ATRIAL-FIBRILLATION; PRACTICE GUIDELINES; CLOPIDOGREL; WARFARIN; ASPIRIN; METAANALYSIS; MANAGEMENT C1 [Ruff, Christian T.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Ruff, Christian T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ruff, CT (reprint author), Harvard Univ, Sch Med, Dept Med, TIMI Study Grp,Cardiovasc Div, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM cruff@partners.org NR 16 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 18 PY 2015 VL 66 IS 7 BP 788 EP 790 DI 10.1016/j.jacc.2015.06.1082 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP5VK UT WOS:000359952900004 PM 26271060 ER PT J AU Burton, DR Saphire, EO AF Burton, Dennis R. Saphire, Erica Ollmann TI Swift antibodies to counter emerging viruses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID ACUTE RESPIRATORY SYNDROME; MONOCLONAL-ANTIBODIES; MIDDLE-EAST; MERS-COV; IDENTIFICATION; CORONAVIRUS; HANTAVIRUS; DISEASES; ILLNESS C1 [Burton, Dennis R.; Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Burton, Dennis R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA. [Saphire, Erica Ollmann] Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Saphire, Erica Ollmann] Viral Hemorrhag Fever Immunotherapeut Consortium, La Jolla, CA 92037 USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM burton@scripps.edu; erica@scripps.edu NR 22 TC 1 Z9 1 U1 2 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 2015 VL 112 IS 33 BP 10082 EP 10083 DI 10.1073/pnas.1513050112 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP2WL UT WOS:000359738300025 PM 26261336 ER PT J AU Dalia, AB Seed, KD Calderwood, SB Camilli, A AF Dalia, Ankur B. Seed, Kimberley D. Calderwood, Stephen B. Camilli, Andrew TI A globally distributed mobile genetic element inhibits natural transformation of Vibrio cholerae SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNase; integrating conjugative element; horizontal gene transfer; evolution ID DNA-SEQUENCE; CLONING; CHITIN; O139 AB Natural transformation is one mechanism of horizontal gene transfer (HGT) in Vibrio cholerae, the causative agent of cholera. Recently, it was found that V. cholerae isolates from the Haiti outbreak were poorly transformed by this mechanism. Here, we show that an integrating conjugative element (ICE)-encoded DNase, which we name IdeA, is necessary and sufficient for inhibiting natural transformation of Haiti outbreak strains. We demonstrate that IdeA inhibits this mechanism of HGT in cis via DNA endonuclease activity that is localized to the periplasm. Furthermore, we show that natural transformation between cholera strains in a relevant environmental context is inhibited by IdeA. The ICE encoding IdeA is globally distributed. Therefore, we analyzed the prevalence and role for this ICE in limiting natural transformation of isolates from Bangladesh collected between 2001 and 2011. We found that IdeA(+) ICEs were nearly ubiquitous in isolates from 2001 to 2005; however, their prevalence decreased to similar to 40% from 2006 to 2011. Thus, IdeA(+) ICEs may have limited the role of natural transformation in V. cholerae. However, the rise in prevalence of strains lacking IdeA may now increase the role of this conserved mechanism of HGT in the evolution of this pathogen. C1 [Dalia, Ankur B.; Camilli, Andrew] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Dalia, Ankur B.; Camilli, Andrew] Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA. [Seed, Kimberley D.] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. [Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Camilli, A (reprint author), Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. EM andrew.camilli@tufts.edu FU US National Institutes of Health [AI055058, AI058935] FX We thank the Tufts Core Facility for sequencing and computational support, and Brian K. Hammer and Eryn Bernardy for providing strains and helpful discussions. This work was supported by US National Institutes of Health Grants AI055058 (to A.C.) and AI058935 (to S.B.C.). A.C. is a Howard Hughes Medical Institute investigator. NR 39 TC 10 Z9 10 U1 3 U2 14 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 AUG 18 PY 2015 VL 112 IS 33 BP 10485 EP 10490 DI 10.1073/pnas.1509097112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP2WL UT WOS:000359738300088 PM 26240317 ER PT J AU Teicholz, JG AF Teicholz, Judith Guss TI Truth and Consequences: What We Lose and Gain in Psychoanalytic Postmodernism SO PSYCHOANALYTIC INQUIRY LA English DT Article ID THERAPEUTIC ACTION; PERSPECTIVE; MULTIPLICITY; SPECIFICITY; NEUTRALITY; THINKING; SYSTEMS; TRAUMA; SELF AB In this article, I use the psychoanalytic concept of truth as a lens through which to explore how psychoanalysis has changed and not changed under the influence of postmodernism. I suggest that the seeking after truth remains in current psychoanalytic practice even though under different guises or conceptual umbrellas, for instance in the high value placed today on authenticity (or trueness) to self and of relationship. Although, admittedly, the search for truth in the sense of compiling historical facts has receded, our current interest in the construction of narratives still comes with the requirement that the stories we co-create with our patients at least have the ring of truth if they are to facilitate psychic growth and psychological intimacy. Additionally, I offer an overview of some of the salient characteristics of postmodern psychoanalysis, with suggestions as to how each of these might relate to the concept of truth. In closing, I borrow a brief clinical vignette from the unpublished notebooks of Melanie Klein for the purpose of making a brief comparison between earlier and current ways of interacting in the treatment relationship. C1 [Teicholz, Judith Guss] Harvard Univ, Sch Med, Dept Psychiat, Clin Fac,Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Teicholz, JG (reprint author), Massachusetts Inst Psychoanal, Cambridge, MA 02138 USA. EM judy_teicholz@yahoo.com NR 107 TC 0 Z9 0 U1 2 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0735-1690 EI 1940-9133 J9 PSYCHOANAL INQ JI Psychoanal. Inq. PD AUG 18 PY 2015 VL 35 IS 6 SI SI BP 639 EP 660 DI 10.1080/07351690.2015.1055223 PG 22 WC Psychology, Psychoanalysis SC Psychology GA CP0UI UT WOS:000359591000007 ER PT J AU McDougle, CJ Landino, SM Vahabzadeh, A O'Rourke, J Zurcher, NR Finger, BC Palumbo, ML Helt, J Mullett, JE Hooker, JM Carlezon, WA AF McDougle, Christopher J. Landino, Samantha M. Vahabzadeh, Arshya O'Rourke, Julia Zurcher, Nicole R. Finger, Beate C. Palumbo, Michelle L. Helt, Jessica Mullett, Jennifer E. Hooker, Jacob M. Carlezon, William A., Jr. TI Toward an immune-mediated subtype of autism spectrum disorder SO BRAIN RESEARCH LA English DT Review DE Autism spectrum disorder; Autoimmune disorders; Neuroimaging; Post-mortem; Animal models; Psychopharmacology; Pathophysiology; Immunology ID PERVASIVE DEVELOPMENTAL DISORDERS; ADRENOCORTICOTROPIC HORMONE 4-9; PROTEIN 18 KDA; DORSOLATERAL PREFRONTAL CORTEX; ORAL HUMAN-IMMUNOGLOBULIN; PLACEBO-CONTROLLED TRIAL; DOUBLE-STRANDED-RNA; AUTOIMMUNE-DISEASES; ANIMAL-MODEL; MICROGLIAL ACTIVATION AB A role for immunological involvement in autism spectrum disorder (ASD) has long been hypothesized. This review includes four sections describing (1) evidence for a relationship between familial autoimmune disorders and ASD; (2) results from post-mortem and neuroimaging studies that investigated aspects of neuroinflammation in ASD; (3) findings from animal model work in ASD involving inflammatory processes; and (4) outcomes from trials of anti-inflammatory/immune-modulating drugs in ASD that have appeared in the literature. Following each section, ideas are provided for future research, suggesting paths forward in the continuing effort to define the role of immune factors and inflammation in the pathophysiology of a subtype of ASD. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. (C) 2014 Elsevier B.V. All rights reserved. C1 [McDougle, Christopher J.; O'Rourke, Julia; Palumbo, Michelle L.; Helt, Jessica; Mullett, Jennifer E.] Lurie Ctr Autism, Lexington, MA 02421 USA. [Landino, Samantha M.; Finger, Beate C.; Carlezon, William A., Jr.] Behav Genet Lab, Belmont, MA USA. [Zurcher, Nicole R.; Hooker, Jacob M.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [McDougle, Christopher J.; Vahabzadeh, Arshya; O'Rourke, Julia; Zurcher, Nicole R.; Palumbo, Michelle L.; Helt, Jessica; Mullett, Jennifer E.; Hooker, Jacob M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Landino, Samantha M.; Vahabzadeh, Arshya; Finger, Beate C.; Carlezon, William A., Jr.] McLean Hosp, Belmont, MA 02178 USA. [McDougle, Christopher J.; Vahabzadeh, Arshya; O'Rourke, Julia; Zurcher, Nicole R.; Finger, Beate C.; Palumbo, Michelle L.; Hooker, Jacob M.; Carlezon, William A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. RP McDougle, CJ (reprint author), Lurie Ctr Autism, Lexington, MA 02421 USA. EM cmcdougle@partners.org FU Nancy Lurie Marks Family Foundation; Robert and Donna Landreth Fund FX This work was funded by the Robert and Donna Landreth Fund with additional support of the Nancy Lurie Marks Family Foundation. NR 137 TC 13 Z9 13 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD AUG 18 PY 2015 VL 1617 SI SI BP 72 EP 92 DI 10.1016/j.brainres.2014.09.048 PG 21 WC Neurosciences SC Neurosciences & Neurology GA CM0DQ UT WOS:000357349000007 PM 25445995 ER PT J AU Williams, KA Swedo, SE AF Williams, Kyle A. Swedo, Susan E. TI Post-infectious autoimmune disorders: Sydenham's chorea, PANDAS and beyond SO BRAIN RESEARCH LA English DT Review DE Sydenhamchorea; PANDAS; Obsessive compulsive disorder; Group A Streptococcus ID OBSESSIVE-COMPULSIVE DISORDER; ACUTE RHEUMATIC-FEVER; THERAPEUTIC PLASMA-EXCHANGE; NEUROPSYCHIATRIC DISORDERS; TOURETTE-SYNDROME; BASAL GANGLIA; STREPTOCOCCAL INFECTIONS; INTRAVENOUS IMMUNOGLOBULIN; PSYCHIATRIC-DISORDERS; BRAIN SPECT AB Infections, and the resulting immune response to these infections, have recently received increased recognition as pathogenic mechanisms for neuropsychiatric disorders. Sydenham's chorea (SC), a widely recognized post-streptococcal autoimmune disorder, represents a model for this proposed pathogenesis. In SC, a dysregulated immune response to a streptococcal infection is hypothesized to result in inflammation of neuronal networks, particularly the basal ganglia nuclei. The resulting dysfunction in the basal ganglia nuclei are hypothesized to lead to a constellation of adventitious movements and psychiatric symptoms, which investigations have shown are amenable to immunomodulatory therapies. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections) has been proposed as a variant of SC, and is hypothesized to share a pathogenic mechanism, despite a unique symptom profile of predominantly psychiatric symptoms. In this review, we present the clinical aspects of both disorders, the data for potential shared etiopathogenesis between them, and the evidence for the therapeutic use of immunomodulatory therapies for the symptoms of SC and PANDAS. This article is part of a Special Issue entitled SI: Neuroirnmunology in Health And Disease. (C) 2014 Elsevier B.V. All rights reserved. C1 [Williams, Kyle A.] Massachusetts Gen Hosp, Pediat Neuropsychiat & Immunol Clin, Dept Psychiat, Boston, MA 02114 USA. [Williams, Kyle A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Williams, KA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Neuropsychiat & Immunol Clin,Dept Psychiat, Boston, MA 02114 USA. EM kwilliams42@partners.org NR 130 TC 14 Z9 14 U1 8 U2 31 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD AUG 18 PY 2015 VL 1617 SI SI BP 144 EP 154 DI 10.1016/j.brainres.2014.09.071 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CM0DQ UT WOS:000357349000011 PM 25301689 ER PT J AU Higuma, T Soeda, T Abe, N Yamada, M Yokoyama, H Shibutani, S Vergallo, R Minami, Y Ong, DS Lee, H Okumura, K Jang, IK AF Higuma, Takumi Soeda, Tsunenari Abe, Naoki Yamada, Masahiro Yokoyama, Hiroaki Shibutani, Shuji Vergallo, Rocco Minami, Yoshiyasu Ong, Daniel S. Lee, Hang Okumura, Ken Jang, Ik-Kyung TI A Combined Optical Coherence Tomography and Intravascular Ultrasound Study on Plaque Rupture, Plaque Erosion, and Calcified Nodule in Patients With ST-Segment Elevation Myocardial Infarction Incidence, Morphologic Characteristics, and Outcomes After Percutaneous Coronary Intervention SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE calcified nodule; intravascular ultrasound; optical coherence tomography; plaque erosion; ST-segment elevation myocardial infarction ID THIN-CAP FIBROATHEROMA; MICROVASCULAR OBSTRUCTION; ATHEROSCLEROTIC PLAQUE; CULPRIT LESION; NO-REFLOW; ACQUISITION; THROMBOSIS; DIAGNOSIS; ARTERIES; DOCUMENT AB OBJECTIVES This study sought to evaluate the incidence of plaque rupture (PR), plaque erosion (PE), and calcified nodule (CN) using optical coherence tomography (OCT) in patients with ST-segment elevation myocardial infarction (STEMI); to compare detailed morphologic plaque characteristics of PR, PE, and CN with optical coherence tomography and intravascular ultrasound; and to compare the post-procedure outcomes among PR, PE, and CN. BACKGROUND The incidence and detailed morphologic characteristics of PR, PE, and CN in STEMI patients and their outcome after percutaneous coronary intervention (PCI) are unknown. METHODS A total of 112 STEMI patients who underwent PCI within 12 h from symptom onset were included. Both optical coherence tomography and intravascular ultrasound were performed following aspiration thrombectomy. RESULTS The incidence of PR, PE, and CN was 64.3%, 26.8%, and 8.0%, respectively. PE and CN, compared with PR, had more fibrous plaque (p < 0.001 and p < 0.001) and less thin-cap fibroatheroma (p < 0.001 and p < 0.001) as well as smaller plaque burden (p = 0.003 and p = 0.001) and remodeling index (p = 0.003 and p < 0.001). PE had greater plaque eccentricity index than PR and CN (p < 0.001 and p < 0.001). CN had greater calcified arc and shallower calcium than PR (p < 0.001 and p < 0.001) or PE (p < 0.001 and p < 0.001). More than one-half of CN had negative remodeling. PE had a lower incidence of no-reflow phenomenon after PCI than PR (p = 0.011). CONCLUSIONS PE was the underlying mechanism in one-fourth of STEMI. PE was characterized by eccentric fibrous plaque. CN was characterized by superficial large calcium and negative remodeling. PE was associated with less microvascular damage after PCI. (C) 2015 by the American College of Cardiology Foundation. C1 [Higuma, Takumi; Abe, Naoki; Yamada, Masahiro; Yokoyama, Hiroaki; Shibutani, Shuji; Okumura, Ken] Hirosaki Univ, Grad Sch Med, Dept Cardiol, Hirosaki, Aomori, Japan. [Soeda, Tsunenari; Vergallo, Rocco; Minami, Yoshiyasu; Ong, Daniel S.; Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Soeda, Tsunenari; Vergallo, Rocco; Minami, Yoshiyasu; Ong, Daniel S.; Lee, Hang; Jang, Ik-Kyung] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Jang, Ik-Kyung] Kyung Hee Univ, Div Cardiol, Seoul, South Korea. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@mgh.harvard.edu FU Mr. and Mrs. Michael Park and Dr. John Nam Research Fellowship grants; Italian Society of Cardiology Award for Research Abroad; St. Jude Medical; Boston Scientific; Medtronic FX This study was supported by Mr. and Mrs. Michael Park and Dr. John Nam Research Fellowship grants. Dr. Vergallo was funded in part by the 2013 Italian Society of Cardiology Award for Research Abroad. Dr. Jang received a research grant and honorarium from St. Jude Medical and received research grants from Boston Scientific and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Higuma and Soeda contributed equally. NR 28 TC 19 Z9 21 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD AUG 17 PY 2015 VL 8 IS 9 BP 1166 EP 1176 DI 10.1016/j.jcin.2015.02.026 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP6RU UT WOS:000360016600009 PM 26117464 ER PT J AU Drachman, DE Beckman, JA AF Drachman, Douglas E. Beckman, Joshua A. TI The Exercise Ankle-Brachial Index A Leap Forward in Noninvasive Diagnosis and Prognosis SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE ankle brachial index; exercise; peripheral artery disease ID PERIPHERAL ARTERY-DISEASE; PREVENTION C1 [Drachman, Douglas E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Beckman, Joshua A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Beckman, JA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM jbeckman@partners.org OI Beckman, Joshua/0000-0001-8332-8439 NR 11 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 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD AUG 17 PY 2015 VL 8 IS 9 BP 1245 EP 1247 DI 10.1016/j.jcin.2015.06.006 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP6RU UT WOS:000360016600019 PM 26292589 ER PT J AU Noiret, L Baigent, S Jalan, R Thomas, SR AF Noiret, Lorette Baigent, Stephen Jalan, Rajiv Thomas, S. Randall TI Mathematical Model of Ammonia Handling in the Rat Renal Medulla SO PLOS ONE LA English DT Article ID THICK ASCENDING LIMB; CHRONIC METABOLIC-ACIDOSIS; RH C GLYCOPROTEIN; NA+-K+-ATPASE; COLLECTING DUCT; INNER MEDULLA; VASA-RECTA; NA+-K+-2CL(-) COTRANSPORTER; JUXTAMEDULLARY NEPHRON; BICARBONATE TRANSPORT AB The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and NH4+, and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts. C1 [Noiret, Lorette; Baigent, Stephen] UCL, CoMPLEX, London, England. [Baigent, Stephen] UCL, Math, London, England. [Jalan, Rajiv] UCL, Sch Med, Inst Hepatol, London W1N 8AA, England. [Thomas, S. Randall] Univ Paris 11, CNRS, IR4M UMR8081, F-91405 Orsay, France. RP Noiret, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02138 USA. EM noiret.lorette@mgh.harvard.edu FU Engineering and Physical Sciences Research Council through the UCL CoMPLEX doctoral training centre; Virtual Physiological Human - Network of Excellence (EU) [23920] FX This work was supported by the Engineering and Physical Sciences Research Council through the UCL CoMPLEX doctoral training centre and by the following grant: The Virtual Physiological Human - Network of Excellence (EU FP7, grant 23920, http://cordis.europa.eu/fp7/ict/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 73 TC 1 Z9 1 U1 0 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 AUG 17 PY 2015 VL 10 IS 8 AR e0134477 DI 10.1371/journal.pone.0134477 PG 28 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP1VK UT WOS:000359664300007 PM 26280830 ER PT J AU Kushibiki, T Tu, YP Abu-Yousif, AO Hasan, T AF Kushibiki, Toshihiro Tu, Yupeng Abu-Yousif, Adnan O. Hasan, Tayyaba TI Photodynamic activation as a molecular switch to promote osteoblast cell differentiation via AP-1 activation SO SCIENTIFIC REPORTS LA English DT Article ID NF-KAPPA-B; MESENCHYMAL STEM-CELLS; INDUCED PROTOPORPHYRIN-IX; KINASE C-THETA; TRANSCRIPTION FACTOR; BONE-FORMATION; GROWTH-FACTOR; ADIPOCYTE DIFFERENTIATION; SIGNAL-TRANSDUCTION; DEATH PATHWAYS AB In photodynamic therapy (PDT), cells are impregnated with a photosensitizing agent that is activated by light irradiation, thereby photochemically generating reactive oxygen species (ROS). The amounts of ROS produced depends on the PDT dose and the nature of the photosensitizer. Although high levels of ROS are cytotoxic, at physiological levels they play a key role as second messengers in cellular signaling pathways, pluripotency, and differentiation of stem cells. To investigate further the use of photochemically triggered manipulation of such pathways, we exposed mouse osteoblast precursor cells and rat primary mesenchymal stromal cells to low-dose PDT. Our results demonstrate that low-dose PDT can promote osteoblast differentiation via the activation of activator protein-1 (AP-1). Although PDT has been used primarily as an anti-cancer therapy, the use of light as a photochemical "molecular switch" to promote differentiation should expand the utility of this method in basic research and clinical applications. C1 [Kushibiki, Toshihiro; Tu, Yupeng; Abu-Yousif, Adnan O.; Hasan, Tayyaba] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kushibiki, Toshihiro] Natl Def Med Coll, Dept Med Engn, Tokorozawa, Saitama 3598513, Japan. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM thasan@mgh.harvard.edu FU National Cancer Institute of the National Institutes of Health [R01CA160998, P01CA084203]; Precursory Research for Embryonic Science and Technology (PRESTO) of the Japan Science and Technology Agency (JST); KAKENHI from Japan Society for the Promotion of Science (JSPS) [21687011, 25713009] FX This research was partially supported by the Precursory Research for Embryonic Science and Technology (PRESTO) of the Japan Science and Technology Agency (JST) and KAKENHI Grant Numbers 21687011 and 25713009 from Japan Society for the Promotion of Science (JSPS). Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers R01CA160998 and P01CA084203. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 60 TC 1 Z9 1 U1 1 U2 8 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 AUG 17 PY 2015 VL 5 AR 13114 DI 10.1038/srep13114 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO9VV UT WOS:000359525200001 PM 26279470 ER PT J AU Parmar, C Grossmann, P Bussink, J Lambin, P Aerts, HJWL AF Parmar, Chintan Grossmann, Patrick Bussink, Johan Lambin, Philippe Aerts, Hugo J. W. L. TI Machine Learning methods for Quantitative Radiomic Biomarkers SO SCIENTIFIC REPORTS LA English DT Article ID CELL LUNG-CANCER; TEXTURAL FEATURES; FEATURE-SELECTION; BREAST-CANCER; SURVIVAL; CLASSIFICATION; PREDICTION; TUMOR; GLIOBLASTOMA; CHEMOTHERAPY AB Radiomics extracts and mines large number of medical imaging features quantifying tumor phenotypic characteristics. Highly accurate and reliable machine-learning approaches can drive the success of radiomic applications in clinical care. In this radiomic study, fourteen feature selection methods and twelve classification methods were examined in terms of their performance and stability for predicting overall survival. A total of 440 radiomic features were extracted from pretreatment computed tomography (CT) images of 464 lung cancer patients. To ensure the unbiased evaluation of different machine-learning methods, publicly available implementations along with reported parameter configurations were used. Furthermore, we used two independent radiomic cohorts for training (n = 310 patients) and validation (n = 154 patients). We identified that Wilcoxon test based feature selection method WLCX (stability = 0.84 +/- 0.05, AUC = 0.65 +/- 0.02) and a classification method random forest RF (RSD = 3.52%, AUC = 0.66 +/- 0.03) had highest prognostic performance with high stability against data perturbation. Our variability analysis indicated that the choice of classification method is the most dominant source of performance variation (34.21% of total variance). Identification of optimal machine-learning methods for radiomic applications is a crucial step towards stable and clinically relevant radiomic biomarkers, providing a non-invasive way of quantifying and monitoring tumor-phenotypic characteristics in clinical practice. C1 [Parmar, Chintan; Grossmann, Patrick; Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Parmar, Chintan; Lambin, Philippe] Maastricht Univ, Res Inst GROW, Radiat Oncol MAASTRO, Maastricht, Netherlands. [Parmar, Chintan] Indian Stat Inst, Machine Intelligence Unit, Kolkata, India. [Grossmann, Patrick; Aerts, Hugo J. W. L.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Bussink, Johan] Radboud Univ Nijmegen, Med Ctr, Dept Radiat Oncol, NL-6525 ED Nijmegen, Netherlands. RP Parmar, C (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. EM Chintan_Parmar@dfci.harvard.edu; Hugo_Aerts@dfci.harvard.edu RI Bussink, Jan/N-3584-2014; Aerts, Hugo/P-6350-2015 OI Aerts, Hugo/0000-0002-2122-2003 FU National Institute of Health (NIH-USA) [U24CA194354, U01CA190234]; EU; Kankeronderzoekfonds Limburg from the Health Foundation Limburg; Dutch Cancer Society [KWF UM 2009-4454, KWF MAC 2013-6425] FX Authors acknowledge financial support from the National Institute of Health (NIH-USA U24CA194354, and NIH-USA U01CA190234), EU 7th framework program (EURECA, ARTFORCE), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society (KWF UM 2009-4454, KWF MAC 2013-6425). NR 41 TC 24 Z9 26 U1 8 U2 29 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 AUG 17 PY 2015 VL 5 AR 13087 DI 10.1038/srep13087 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO9VL UT WOS:000359524200001 PM 26278466 ER PT J AU Liu, N Wood, KB Schwab, JH Cha, TD Pedlow, FX Puhkan, RD Hyzog, TL AF Liu, Ning Wood, Kirkham B. Schwab, Joseph H. Cha, Thomas D. Pedlow, Frank X., Jr. Puhkan, Rishabh D. Hyzog, Tylor L. TI Utility of Flexion-Extension Radiographs in Lumbar Spondylolisthesis A Prospective Study SO SPINE LA English DT Article DE spondylolisthesis; lumbar; stability; instability; flexion; extension; diagnostic modality; radiography; magnetic resonance imaging; supine ID INSTABILITY; SPINE; INDIVIDUALS AB Study Design. Prospective cohort study in consecutive patients. Objective. To investigate and compare the use of 2 diagnostic modalities in the evaluation of stability in lumbar spondylolisthesis. Summary of Background Data. Evaluating potential instability in lumbar spondylolisthesis is significant to its management. Lateral lumbar flexion-extension (FE) radiograph is frequently obtained on the basis of a thought that this forward-backward movement can actually describe hypermobility at the listhetic segment. However, simply comparing standard upright lumbar lateral radiograph (U) with a supine sagittal magnetic resonance image (S) (combined, US), something typically conducted for patients with lumbar spondylolisthesis, may also be used. Methods. This prospective study included a cohort of 68 consecutive patients with lumbar spondylolisthesis seen in the outpatient clinic of a single hospital. The mobility observed in US was compared with that observed in FE. The ability to identify "instability" using US was compared with that using FE. In addition, the relationships between mobility determined using FE or US and sex, age, height, weight, body mass index, primary symptom (with or without back pain), nature of spondylolisthesis (degenerative or isthmic), listhetic segment, slippage grade, and focal disc height were examined. Results. Overall, the mobility in US was significantly higher than that in FE (7.68 +/- 5.34% vs. 4.90 +/- 3.82%, t = -3.545, P = 0.001). The ability to identify "instability" on the basis of US was improved compared with that obtained using FE. Female patients demonstrated higher mobility in FE than male patients to a signifi cant degree. Back pain, isthmic spondylolisthesis, and slippage grade also showed some relevance with mobility but without statistical significance. Conclusion. US may offer an easily available, alternative diagnostic modality in lumbar spondylolisthesis, with the potential of reducing both radiation exposure and costs. Further studies should focus on its influence in clinical decision making. C1 [Liu, Ning; Wood, Kirkham B.; Schwab, Joseph H.; Cha, Thomas D.; Pedlow, Frank X., Jr.; Puhkan, Rishabh D.; Hyzog, Tylor L.] Massachusetts Gen Hosp, Spine Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Wood, KB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Spine Serv, 55 Fruit St,Yawkey Ctr,Ste 3800, Boston, MA 02114 USA. EM kbwood@mgh.harvard.edu NR 14 TC 2 Z9 2 U1 5 U2 5 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 AUG 15 PY 2015 VL 40 IS 16 BP E929 EP E935 DI 10.1097/BRS.0000000000000941 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DC4WC UT WOS:000369220000003 PM 25893348 ER PT J AU Haghighi, F Ge, YC Chen, S Xin, YR Umali, MU De Gasperi, R Sosa, MAG Ahlers, ST Elder, GA AF Haghighi, Fatemeh Ge, Yongchao Chen, Sean Xin, Yurong Umali, Michelle U. De Gasperi, Rita Sosa, Miguel A. Gama Ahlers, Stephen T. Elder, Gregory A. TI Neuronal DNA Methylation Profiling of Blast-Related Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE blast overpressure; DNA methylation; epigenetic; sleep disturbance; traumatic brain injury ID SLEEP DISTURBANCE; INTRACRANIAL-PRESSURE; N-ACETYLTRANSFERASE; INDUCED NEUROTRAUMA; NITRIC-OXIDE; MOUSE MODEL; RAT MODEL; EXPOSURE; EXPRESSION; MICE AB Long-term molecular changes in the brain resulting from blast exposure may be mediated by epigenetic changes, such as deoxyribonucleic acid (DNA) methylation, that regulate gene expression. Aberrant regulation of gene expression is associated with behavioral abnormalities, where DNA methylation bridges environmental signals to sustained changes in gene expression. We assessed DNA methylation changes in the brains of rats exposed to three 74.5kPa blast overpressure events, conditions that have been associated with long-term anxiogenic manifestations weeks or months following the initial exposures. Rat frontal cortex eight months post-exposure was used for cell sorting of whole brain tissue into neurons and glia. We interrogated DNA methylation profiles in these cells using Expanded Reduced Representation Bisulfite Sequencing. We obtained data for millions of cytosines, showing distinct methylation profiles for neurons and glia and an increase in global methylation in neuronal versus glial cells (p<10(-7)). We detected DNA methylation perturbations in blast overpressure-exposed animals, compared with sham blast controls, within 458 and 379 genes in neurons and glia, respectively. Differentially methylated neuronal genes showed enrichment in cell death and survival and nervous system development and function, including genes involved in transforming growth factor and nitric oxide signaling. Functional validation via gene expression analysis of 30 differentially methylated neuronal and glial genes showed a 1.2 fold change in gene expression of the serotonin N-acetyltransferase gene (Aanat) in blast animals (p<0.05). These data provide the first genome-based evidence for changes in DNA methylation induced in response to multiple blast overpressure exposures. In particular, increased methylation and decreased gene expression were observed in the Aanat gene, which is involved in converting serotonin to the circadian hormone melatonin and is implicated in sleep disturbance and depression associated with traumatic brain injury. C1 [Haghighi, Fatemeh] James J Peters Dept Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. [De Gasperi, Rita; Sosa, Miguel A. Gama] James J Peters Dept Vet Affairs Med Ctr, Res & Dev Serv, Bronx, NY USA. [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY USA. [Haghighi, Fatemeh; Chen, Sean; Xin, Yurong; Umali, Michelle U.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Haghighi, Fatemeh; De Gasperi, Rita; Sosa, Miguel A. Gama; Elder, Gregory A.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Ge, Yongchao; Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [De Gasperi, Rita; Sosa, Miguel A. Gama; Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Ahlers, Stephen T.] Naval Med Res Ctr, Operat & Undersea Med Directorate, Dept Neurotrauma, Silver Spring, MD USA. RP Haghighi, F (reprint author), Icahn Sch Med Mt Sinai, 1425 Madison Ave,Floor 10,Room 10-70D, New York, NY 10029 USA. EM fatemeh.haghighi@mssm.edu FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Award [1I01RX000996-01]; [MH094774] FX This work was supported by MH094774 and the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Award 1I01RX000996-01. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. The study protocol was reviewed and approved by the Walter Reed Army Institute of Research/Naval Medical Research Center Institutional Animal Care and Use Committee in compliance with all applicable Federal regulations governing the protection of animals in research. NR 74 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG 15 PY 2015 VL 32 IS 16 BP 1200 EP 1209 DI 10.1089/neu.2014.3640 PG 10 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CU9RU UT WOS:000363883400003 PM 25594545 ER PT J AU Hammond, FM Sherer, M Malec, JF Zafonte, RD Whitney, M Bell, K Dikmen, S Bogner, J Mysiw, J Pershad, R AF Hammond, Flora M. Sherer, Mark Malec, James F. Zafonte, Ross D. Whitney, Marybeth Bell, Kathleen Dikmen, Sureyya Bogner, Jennifer Mysiw, Jerry Pershad, Rashmi CA Amantadine Irritability Multisite TI Amantadine Effect on Perceptions of Irritability after Traumatic Brain Injury: Results of the Amantadine Irritability Multisite Study SO JOURNAL OF NEUROTRAUMA LA English DT Article DE agitation; aggression; amantadine; brain injuries; irritability ID NEUROPSYCHIATRIC INVENTORY; BEHAVIOR-CHANGE; SCALE; REHABILITATION; ALLIANCE; DISEASE; TRIALS AB This study examines the effect of amantadine on irritability in persons in the post-acute period after traumatic brain injury (TBI). There were 168 persons 6 months post-TBI with irritability who were enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial receiving either amantadine 100mg twice daily or equivalent placebo for 60 days. Subjects were assessed at baseline and days 28 (primary end-point) and 60 of treatment using observer-rated and participant-rated Neuropsychiatric Inventory (NPI-I) Most Problematic item (primary outcome), NPI Most Aberrant item, and NPI-I Distress Scores, as well as physician-rated Clinical Global Impressions (CGI) scale. Observer ratings between the two groups were not statistically significantly different at day 28 or 60; however, observers rated the majority in both groups as having improved at both intervals. Participant ratings for day 60 demonstrated improvements in both groups with greater improvement in the amantadine group on NPI-I Most Problematic (p<0.04) and NPI-I Distress (p<0.04). These results were not significant with correction for multiple comparisons. CGI demonstrated greater improvement for amantadine than the placebo group (p<0.04). Adverse event occurrence did not differ between the two groups. While observers in both groups reported large improvements, significant group differences were not found for the primary outcome (observer ratings) at either day 28 or 60. This large placebo or nonspecific effect may have masked detection of a treatment effect. The result of this study of amantadine 100mg every morning and noon to reduce irritability was not positive from the observer perspective, although there are indications of improvement at day 60 from the perspective of persons with TBI and clinicians that may warrant further investigation. C1 [Hammond, Flora M.; Malec, James F.] Indiana Univ Sch Med, Dept Phys Med & Rehabil, Indianapolis, IN 46254 USA. [Hammond, Flora M.; Malec, James F.] Rehabil Hosp Indiana, Indianapolis, IN USA. [Hammond, Flora M.; Whitney, Marybeth; Pershad, Rashmi] Carolinas HealthCare Syst, Carolinas Rehabil, Dept Phys Med & Rehabil, Charlotte, NC USA. [Sherer, Mark] TIRR Mem Hermann, Houston, TX USA. [Zafonte, Ross D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. [Zafonte, Ross D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bell, Kathleen; Dikmen, Sureyya] Univ Washington, Seattle, WA 98195 USA. [Bogner, Jennifer; Mysiw, Jerry] Ohio State Univ, Dept Phys Med & Rehabil, Columbus, OH 43210 USA. [Bell, Kathleen] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Hammond, FM (reprint author), Indiana Univ Sch Med, Rehabil Hosp Indiana, Carolinas Rehabil, 4141 Shore Dr, Indianapolis, IN 46254 USA. EM Flora.hammond@rhin.com FU US Department of Education, Office of Special Education and Rehabilitative Services, National Institute on Disability and Rehabilitation Research [H133A080035] FX The research reported in this article was supported by US Department of Education, Office of Special Education and Rehabilitative Services, National Institute on Disability and Rehabilitation Research grant H133A080035. This support included the funds to purchase amantadine. The study sponsor had no role in the design and conduct of this study; the collection, management, analysis, and interpretation of the data; or the preparation review, or approval of the manuscript. NR 26 TC 6 Z9 6 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG 15 PY 2015 VL 32 IS 16 BP 1230 EP 1238 DI 10.1089/neu.2014.3803 PG 9 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CU9RU UT WOS:000363883400007 PM 25774566 ER PT J AU Camp, ER Ellis, LM AF Camp, E. Ramsay Ellis, Lee M. TI CCR 20th Anniversary Commentary: RAS as a Biomarker for EGFR-Targeted Therapy for Colorectal Cancer-From Concept to Practice SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; MUTATIONS; CETUXIMAB; ANTIBODY; KRAS; RESISTANCE; GEFITINIB; ERLOTINIB; BENEFIT AB Clinical data support the use of EGFR mAbs in patients with metastatic colorectal cancer (mCRC) with wild-type RAS status. This notion, hypothesized in the review article by Camp, Ellis, and colleagues in the January 1, 2005, issue of Clinical Cancer Research, serves as an example of the successful application of basic science principles to clinical practice. The exclusion of patients with mCRC with Ras-mutated tumors from therapy with EGFR mAbs has led to improved outcomes while sparing patients unnecessary and potentially harmful therapy. (C)2015 AACR. C1 [Camp, E. Ramsay] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Camp, E. Ramsay] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Camp, E. Ramsay] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Ellis, Lee M.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Ellis, Lee M.] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. RP Ellis, LM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Unit 1484, POB 301402,1515 Holcombe Blvd, Houston, TX 77230 USA. EM lellis@mdanderson.org FU NCI NIH HHS [CA100879, K08 CA142904, K08CA142904, R01 CA157880, R01CA157880] NR 14 TC 2 Z9 2 U1 1 U2 2 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 AUG 15 PY 2015 VL 21 IS 16 BP 3578 EP 3580 DI 10.1158/1078-0432.CCR-14-2900 PG 3 WC Oncology SC Oncology GA CS2NX UT WOS:000361909100002 PM 26275951 ER PT J AU Lee, EQ Kaley, TJ Duda, DG Schiff, D Lassman, AB Wong, ET Mikkelsen, T Purow, BW Muzikansky, A Ancukiewicz, M Huse, JT Ramkissoon, S Drappatz, J Norden, AD Beroukhim, R Weiss, SE Alexander, BM McCluskey, CS Gerard, M Smith, KH Jain, RK Batchelor, TT Ligon, KL Wen, PY AF Lee, Eudocia Q. Kaley, Thomas J. Duda, Dan G. Schiff, David Lassman, Andrew B. Wong, Eric T. Mikkelsen, Tom Purow, Benjamin W. Muzikansky, Alona Ancukiewicz, Marek Huse, Jason T. Ramkissoon, Shakti Drappatz, Jan Norden, Andrew D. Beroukhim, Rameen Weiss, Stephanie E. Alexander, Brian M. McCluskey, Christine S. Gerard, Mary Smith, Katrina H. Jain, Rakesh K. Batchelor, Tracy T. Ligon, Keith L. Wen, Patrick Y. TI A Multicenter, Phase II, Randomized, Noncomparative Clinical Trial of Radiation and Temozolomide with or without Vandetanib in Newly Diagnosed Glioblastoma Patients SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; DOUBLE-BLIND; MALIGNANT GLIOMA; THYROID-CANCER; TUMOR-GROWTH; I/II TRIAL; ZD6474; RADIOTHERAPY AB Purpose: Vandetanib, a tyrosine kinase inhibitor of KDR (VEGFR2), EGFR, and RET, may enhance sensitivity to chemotherapy and radiation. We conducted a randomized, noncomparative, phase II study of radiation (RT) and temozolomide with or without vandetanib in patients with newly diagnosed glioblastoma (GBM). Experimental Design: We planned to randomize a total of 114 newly diagnosed GBM patients in a ratio of 2: 1 to standard RT and temozolomide with (76 patients) or without (38 patients) vandetanib 100 mg daily. Patients with age >= 18 years, Karnofsky performance status (KPS) >= 60, and not on enzyme-inducing antiepileptics were eligible. Primary end-point was median overall survival (OS) from the date of randomization. Secondary endpoints included median progression-free survival (PFS), 12-month PFS, and safety. Correlative studies included pharmacokinetics as well as tissue and serum biomarker analysis. Results: The study was terminated early for futility based on the results of an interim analysis. We enrolled 106 patients (36 in the RT/temozolomide arm and 70 in the vandetanib/RT/temozolomide arm). Median OS was 15.9 months [95% confidence interval (CI), 11.0-22.5 months] in the RT/temozolomide arm and 16.6 months (95% CI, 14.9-20.1 months) in the vandetanib/RT/temozolomide (log-rank P = 0.75). Conclusions: The addition of vandetanib at a dose of 100 mg daily to standard chemoradiation in patients with newly diagnosed GBM or gliosarcoma was associated with potential pharmacodynamic biomarker changes and was reasonably well tolerated. However, the regimen did not significantly prolong OS compared with the parallel control arm, leading to early termination of the study. (C)2015 AACR. C1 [Lee, Eudocia Q.; Ramkissoon, Shakti; Norden, Andrew D.; Beroukhim, Rameen; Alexander, Brian M.; McCluskey, Christine S.; Gerard, Mary; Smith, Katrina H.; Ligon, Keith L.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Lee, Eudocia Q.; Duda, Dan G.; Wong, Eric T.; Muzikansky, Alona; Ramkissoon, Shakti; Norden, Andrew D.; Beroukhim, Rameen; Alexander, Brian M.; Jain, Rakesh K.; Batchelor, Tracy T.; Ligon, Keith L.; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. [Kaley, Thomas J.; Huse, Jason T.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Duda, Dan G.; Muzikansky, Alona; Ancukiewicz, Marek; Jain, Rakesh K.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schiff, David; Purow, Benjamin W.] Univ Virginia, Charlottesville, VA USA. [Lassman, Andrew B.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Wong, Eric T.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Drappatz, Jan] Univ Pittsburgh, Med Ctr, Ctr Canc, Pittsburgh, PA USA. [Weiss, Stephanie E.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Patrick_Wen@dfci.harvard.edu OI Kaley, Thomas/0000-0002-2540-8518 FU AstraZeneca FX This research was conducted with support from the Investigator-Sponsored Study Program of AstraZeneca. NR 45 TC 7 Z9 7 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2015 VL 21 IS 16 BP 3610 EP 3618 DI 10.1158/1078-0432.CCR-14-3220 PG 9 WC Oncology SC Oncology GA CS2NX UT WOS:000361909100009 PM 25910950 ER PT J AU GuhaThakurta, D Sheikh, NA Fan, LQ Kandadi, H Meagher, TC Hall, SJ Kantoff, PW Higano, CS Small, EJ Gardner, TA Bailey, K Vu, T DeVries, T Whitmore, JB Frohlich, MW Trager, JB Drake, CG AF GuhaThakurta, Debraj Sheikh, Nadeem A. Fan, Li-Qun Kandadi, Harini Meagher, T. Craig Hall, Simon J. Kantoff, Philip W. Higano, Celestia S. Small, Eric J. Gardner, Thomas A. Bailey, Kate Vu, Tuyen DeVries, Todd Whitmore, James B. Frohlich, Mark W. Trager, James B. Drake, Charles G. TI Humoral Immune Response against Nontargeted Tumor Antigens after Treatment with Sipuleucel-T and Its Association with Improved Clinical Outcome SO CLINICAL CANCER RESEARCH LA English DT Article ID RESISTANT PROSTATE-CANCER; IMMUNOGLOBULIN-KAPPA C; GENE-EXPRESSION; END-POINTS; IMMUNOTHERAPY TRIALS; PROTEIN MICROARRAYS; ADVANCED MELANOMA; PROGNOSTIC MODEL; SOLID TUMORS; SURVIVAL AB Purpose: Antitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen). Experimental Design: Serum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses were subsequently validated in ProACT (n = 33), an independent phase II study of sipuleucel-T. Association of IgG responses with overall survival (OS) was assessed using multivariate Cox models adjusted for baseline prostate-specific antigen (PSA) and lactate dehydrogenase levels. Results: In patients from IMPACT and ProACT, levels of IgG against multiple secondary antigens, including PSA, KLK2/hK2, K-Ras, E-Ras, LGALS8/PCTA-1/galectin-8, and LGALS3/galectin-3, were elevated after treatment with sipuleucel-T (P < 0.01), but not control. IgG responses (>= 2-fold elevation post-treatment) occurred in >= 25% of patients, appeared by 2 weeks after sipuleucel-T treatment, and persisted for up to 6 months. IgG responses to PSA and LGALS3 were associated with improved OS in sipuleucel-T-treated patients from IMPACT (P <= 0.05). Conclusions: Sipuleucel-T induced humoral antigen spread in patients with mCRPC. IgG responses were associated with improved OS in IMPACT. The methods and results reported may identify pharmacodynamic biomarkers of clinical outcome after sipuleucel-T treatment, and help in clinical assessments of other cancer immunotherapies. (C) 2015 AACR. C1 [GuhaThakurta, Debraj; Sheikh, Nadeem A.; Fan, Li-Qun; Kandadi, Harini; Meagher, T. Craig; Bailey, Kate; Vu, Tuyen; DeVries, Todd; Whitmore, James B.; Frohlich, Mark W.; Trager, James B.] Dendreon Corp, Seattle, WA USA. [Hall, Simon J.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Higano, Celestia S.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Higano, Celestia S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Small, Eric J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gardner, Thomas A.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Drake, Charles G.] Johns Hopkins Univ, Sch Med, Brady Urol Inst, Baltimore, MD USA. RP Drake, CG (reprint author), Johns Hopkins Univ, Sch Med, 1650 Orleans St,CRB 410, Baltimore, MD 21231 USA. EM jtrager@dendreon.com; cdrake@jhmi.edu FU Dendreon Corporation FX Funding for the study was provided by Dendreon Corporation. NR 64 TC 19 Z9 19 U1 0 U2 1 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 AUG 15 PY 2015 VL 21 IS 16 BP 3619 EP 3630 DI 10.1158/1078-0432.CCR-14-2334 PG 12 WC Oncology SC Oncology GA CS2NX UT WOS:000361909100010 PM 25649018 ER PT J AU Ceccaldi, R O'Connor, K Mouw, KW Li, AY Matulonis, UA D'Andrea, AD Konstantinopoulos, PA AF Ceccaldi, Raphael O'Connor, Kevin Mouw, Kent W. Li, Adam Y. Matulonis, Ursula A. D'Andrea, Alan D. Konstantinopoulos, Panagiotis A. TI Nucleotide excision repair mutations confer sensitivity to platinum but not PARP-inhibitors in epithelial ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 10th Biennial Ovarian Cancer Research Symposium CY SEP 08-09, 2014 CL Seattle, WA C1 [Ceccaldi, Raphael; O'Connor, Kevin; Mouw, Kent W.; Li, Adam Y.; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Cambridge, MA 02138 USA. [Mouw, Kent W.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Cambridge, MA 02138 USA. [Matulonis, Ursula A.; Konstantinopoulos, Panagiotis A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Med Gynecol Oncol Program, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 4 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 AUG 15 PY 2015 VL 21 SU 16 MA BIOL-1331 DI 10.1158/1557-3265.OVCASYMP14-POSTER-BIOL-1331 PG 1 WC Oncology SC Oncology GA CR5MD UT WOS:000361386100091 ER PT J AU Hahn, WC AF Hahn, William C. TI Functional genomics, cancer biology and targets SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 10th Biennial Ovarian Cancer Research Symposium CY SEP 08-09, 2014 CL Seattle, WA C1 [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Hahn, William C.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Hahn, William C.] MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 AUG 15 PY 2015 VL 21 SU 16 MA KP02 DI 10.1158/1557-3265.OVCASYMP14-KP02 PG 1 WC Oncology SC Oncology GA CR5MD UT WOS:000361386100030 ER PT J AU Howitt, BE Hanamornroongruang, S Lin, D Conner, JE Schulte, S Garber, J Crum, CP Meserve, EE AF Howitt, Brooke E. Hanamornroongruang, Suchanan Lin, Douglas Conner, James E. Schulte, Stephanie Garber, Judy Crum, Christopher P. Meserve, Emily E. TI A dualistic model for the origin of high-grade serous carcinoma: BRCA mutation status, histology and tubal intraepithelial carcinoma SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 10th Biennial Ovarian Cancer Research Symposium CY SEP 08-09, 2014 CL Seattle, WA C1 [Howitt, Brooke E.; Lin, Douglas; Conner, James E.; Schulte, Stephanie; Crum, Christopher P.; Meserve, Emily E.] Brigham & Womens Hosp, Div Womens & Perinatal Pathol, Dept Pathol, Boston, MA 02115 USA. [Hanamornroongruang, Suchanan] Dept Pathol, Bangkok, Thailand. [Garber, Judy] Dana Farber Canc Inst, Div Canc Epidemiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 AUG 15 PY 2015 VL 21 SU 16 MA CTRL-1208 DI 10.1158/1557-3265.OVCASYMP14-POSTER-CTRL-1208 PG 1 WC Oncology SC Oncology GA CR5MD UT WOS:000361386100057 ER PT J AU Litovchick, L Saini, S Karst, A Hu, L Drapkin, R DeCaprio, JA AF Litovchick, Larisa Saini, Siddharth Karst, Alison Hu, Lan Drapkin, Ronny DeCaprio, James A. TI Loss of DYRK1A promotes transformation of the fallopian tube epithelial cells by oncogenic ras SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 10th Biennial Ovarian Cancer Research Symposium CY SEP 08-09, 2014 CL Seattle, WA C1 [Litovchick, Larisa; Saini, Siddharth] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23298 USA. [Karst, Alison; Drapkin, Ronny; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Karst, Alison; Drapkin, Ronny; DeCaprio, James A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Hu, Lan] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 2 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 AUG 15 PY 2015 VL 21 SU 16 MA BIOL-1324A DI 10.1158/1557-3265.OVCASYMP14-POSTER-BIOL-1324A PG 1 WC Oncology SC Oncology GA CR5MD UT WOS:000361386100086 ER PT J AU Perets, R Wyant, GA Ohman, AW Setlur, SR Crum, CP Drapkin, R Dinulescu, DM AF Perets, Ruth Wyant, Gregory A. Ohman, Anders W. Setlur, Sunita R. Crum, Christopher P. Drapkin, Ronny Dinulescu, Daniela M. TI Novel strategies for targeting high-grade serous ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 10th Biennial Ovarian Cancer Research Symposium CY SEP 08-09, 2014 CL Seattle, WA C1 [Perets, Ruth; Drapkin, Ronny] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02215 USA. [Wyant, Gregory A.; Ohman, Anders W.; Setlur, Sunita R.; Dinulescu, Daniela M.] Harvard Univ, Sch Med, Eugene Braunwald Res Ctr, Boston, MA 02115 USA. [Wyant, Gregory A.; Ohman, Anders W.; Setlur, Sunita R.; Crum, Christopher P.; Drapkin, Ronny; Dinulescu, Daniela M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Div Womens & Perinatal Pathol, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 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 AUG 15 PY 2015 VL 21 SU 16 MA CTRL-1204 DI 10.1158/1557-3265.OVCASYMP14-POSTER-CTRL-1204 PG 2 WC Oncology SC Oncology GA CR5MD UT WOS:000361386100054 ER PT J AU Sheets, JN Iwanicki, M Liu, J Drapkin, R Egland, KA AF Sheets, Jordan N. Iwanicki, Marcin Liu, Joyce Drapkin, Ronny Egland, Kristi A. TI SUSD2 inhibits spheroids from breaching the mesothelium: a mechanism for increased longevity of patients with SUSD2-expressing high-grade ovarian serous carcinoma SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 10th Biennial Ovarian Cancer Research Symposium CY SEP 08-09, 2014 CL Seattle, WA C1 [Sheets, Jordan N.; Egland, Kristi A.] Univ S Dakota, Sanford Sch Med, Sanford Res, Canc Biol Res Ctr, Sioux Falls, SD USA. [Iwanicki, Marcin] Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. [Liu, Joyce; Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Iwanicki, Marcin; Liu, Joyce; Drapkin, Ronny] Harvard Univ, Sch Med, Boston, MA USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2015 VL 21 SU 16 MA BIOL-1345 DI 10.1158/1557-3265.OVCASYMP14-POSTER-BIOL-1345 PG 2 WC Oncology SC Oncology GA CR5MD UT WOS:000361386100100 ER PT J AU Tangutoori, S Baldwin, P Medina, J Ohman, A Dinulescu, D Sridhar, S AF Tangutoori, Shifalika Baldwin, Paige Medina, Jamie Ohman, Anders Dinulescu, Daniela Sridhar, Srinivas TI PARP inhibitor nano-therapy in ovarian cancer models SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 10th Biennial Ovarian Cancer Research Symposium CY SEP 08-09, 2014 CL Seattle, WA C1 [Tangutoori, Shifalika; Baldwin, Paige; Sridhar, Srinivas] Northeastern Univ, Nanomed Sci & Technol Ctr, Boston, MA USA. [Tangutoori, Shifalika] Dana Farber Canc Inst, Boston, MA USA. [Medina, Jamie; Ohman, Anders; Dinulescu, Daniela] Brigham & Womens Hosp, Boston, MA 02115 USA. [Medina, Jamie; Ohman, Anders; Dinulescu, Daniela; Sridhar, Srinivas] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 AUG 15 PY 2015 VL 21 SU 16 MA AS29 DI 10.1158/1557-3265.OVCASYMP14-AS29 PG 2 WC Oncology SC Oncology GA CR5MD UT WOS:000361386100025 ER PT J AU Nettleton, JA Follis, JL Ngwa, JS Smith, CE Ahmad, S Tanaka, T Wojczynski, MK Voortman, T Lemaitre, RN Kristiansson, K Nuotio, ML Houston, DK Perala, MM Qi, QB Sonestedt, E Manichaikul, A Kanoni, S Ganna, A Mikkila, V North, KE Siscovick, DS Harald, K Mckeown, NM Johansson, I Rissanen, H Liu, YM Lahti, J Hu, FB Bandinelli, S Rukh, G Rich, S Booij, L Dmitriou, M Ax, E Raitakari, O Mukamal, K Mannisto, S Hallmans, G Jula, A Ericson, U Jacobs, DR Van Rooij, FJA Deloukas, P Sjogren, P Kahonen, M Djousse, L Perola, M Barroso, I Hofman, A Stirrups, K Viikari, J Uitterlinden, AG Kalafati, IP Franco, OH Mozaffarian, D Salomaa, V Borecki, IB Knekt, P Kritchevsky, SB Eriksson, JG Dedoussis, GV Qi, L Ferrucci, L Orho-Melander, M Zillikens, MC Ingelsson, E Lehtimaki, T Renstrom, F Cupples, LA Loos, RJF Franks, PW AF Nettleton, Jennifer A. Follis, Jack L. Ngwa, Julius S. Smith, Caren E. Ahmad, Shafqat Tanaka, Toshiko Wojczynski, Mary K. Voortman, Trudy Lemaitre, Rozenn N. Kristiansson, Kati Nuotio, Marja-Liisa Houston, Denise K. Perala, Mia-Maria Qi, Qibin Sonestedt, Emily Manichaikul, Ani Kanoni, Stavroula Ganna, Andrea Mikkila, Vera North, Kari E. Siscovick, David S. Harald, Kennet Mckeown, Nicola M. Johansson, Ingegerd Rissanen, Harri Liu, Yongmei Lahti, Jari Hu, Frank B. Bandinelli, Stefania Rukh, Gull Rich, Stephen Booij, Lisanne Dmitriou, Maria Ax, Erika Raitakari, Olli Mukamal, Kenneth Mannisto, Satu Hallmans, Goran Jula, Antti Ericson, Ulrika Jacobs, David R., Jr. Van Rooij, Frank J. A. Deloukas, Panos Sjogren, Per Kahonen, Mika Djousse, Luc Perola, Markus Barroso, Ines Hofman, Albert Stirrups, Kathleen Viikari, Jorma Uitterlinden, Andre G. Kalafati, Ioanna P. Franco, Oscar H. Mozaffarian, Dariush Salomaa, Veikko Borecki, Ingrid B. Knekt, Paul Kritchevsky, Stephen B. Eriksson, Johan G. Dedoussis, George V. Qi, Lu Ferrucci, Luigi Orho-Melander, Marju Zillikens, M. Carola Ingelsson, Erik Lehtimaki, Terho Renstrom, Frida Cupples, L. Adrienne Loos, Ruth J. F. Franks, Paul W. TI Gene x dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry SO HUMAN MOLECULAR GENETICS LA English DT Article ID BODY-MASS INDEX; DIABETES PREVENTION PROGRAM; PHYSICAL-ACTIVITY; ENVIRONMENT INTERACTIONS; GLUCOSE-HOMEOSTASIS; FASTING GLUCOSE; WEIGHT-LOSS; LOCI; METAANALYSIS; INDIVIDUALS AB Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance. C1 [Nettleton, Jennifer A.] Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Follis, Jack L.] Univ St Thomas, Dept Math, Houston, TX 77006 USA. [Ngwa, Julius S.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Smith, Caren E.; Mckeown, Nicola M.] Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA. [Smith, Caren E.; Mckeown, Nicola M.; Mozaffarian, Dariush] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Ahmad, Shafqat; Renstrom, Frida; Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Sonestedt, Emily; Rukh, Gull; Ericson, Ulrika; Orho-Melander, Marju] Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Wojczynski, Mary K.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Voortman, Trudy; Van Rooij, Frank J. A.; Hofman, Albert; Franco, Oscar H.] Erasmus MC, Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Voortman, Trudy; Booij, Lisanne; Van Rooij, Frank J. A.; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Zillikens, M. Carola] NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands. [Lemaitre, Rozenn N.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Kristiansson, Kati; Nuotio, Marja-Liisa; Perola, Markus] Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki 00290, Finland. [Perala, Mia-Maria; Mannisto, Satu; Eriksson, Johan G.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00290, Finland. [Nuotio, Marja-Liisa; Perola, Markus] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland. [Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Qi, Qibin; Hu, Frank B.; Qi, Lu; Franks, Paul W.] Harvard Univ, Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Qi, Qibin] Albert Einstein Coll Med, Dept Epidemiol & Publ Hlth, Bronx, NY 10467 USA. [Manichaikul, Ani; Rich, Stephen] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Manichaikul, Ani] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA. [Kanoni, Stavroula; Stirrups, Kathleen] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. [Ganna, Andrea] Karolinska Inst, Dept Med Epidemiol & Biostatist, Stockholm, Sweden. [Mikkila, Vera] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland. [Lahti, Jari] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Inst Clin Med, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Mikkila, Vera; Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. [Harald, Kennet; Rissanen, Harri; Jula, Antti; Salomaa, Veikko; Knekt, Paul] THL Natl Inst Hlth & Welf, Helsinki 00300, Finland. [Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, Umea, Sweden. [Renstrom, Frida] Umea Univ, Dept Biobank Res, Umea, Sweden. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Lahti, Jari; Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy. [Booij, Lisanne; Uitterlinden, Andre G.; Zillikens, M. Carola] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Dmitriou, Maria; Kalafati, Ioanna P.; Dedoussis, George V.] Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece. [Ax, Erika; Sjogren, Per] Uppsala Univ, Dept Publ Hlth & Caring Sci Clin Nutr & Metab, Uppsala, Sweden. [Ingelsson, Erik] Uppsala Univ, Dept Med Sci Mol Epidemiol, Uppsala, Sweden. [Ingelsson, Erik] Uppsala Univ, Sci Life Lab, Uppsala, Sweden. [Raitakari, Olli] Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, Div Med, FIN-20520 Turku, Finland. [Mukamal, Kenneth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Kahonen, Mika] Tampere Univ Hosp, Tampere, Finland. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Djousse, Luc] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA. [Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Barroso, Ines] Wellcome Trust Sanger Inst, Metab Dis Grp, Hinxton, Cambs, England. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England. [Eriksson, Johan G.] Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Franks, PW (reprint author), Skane Univ Hosp Malmo, CRC, Dept Clin Sci Genet & Mol Epidemiol, Bldg 91,Level 10,Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden. EM paul.franks@med.lu.se RI Sonestedt, Emily/I-3814-2016; Voortman, Trudy/C-2963-2015; Deloukas, Panos/B-2922-2013; Djousse, Luc/F-5033-2017 OI Sonestedt, Emily/0000-0002-0747-4562; Voortman, Trudy/0000-0003-2830-6813; Deloukas, Panos/0000-0001-9251-070X; Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute [R01HL105756]; Nutrition Working Group within CHARGE; career development award from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [5K01DK082729-04]; Distinguished Young Research Award in Medicine from the Swedish Research Council; EXODIAB; Swedish Research Council FX Infrastructure for the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium was supported in part by the National Heart, Lung, and Blood Institute Grant No. R01HL105756. Each cohort participating in the present investigation, conducted by the Nutrition Working Group within CHARGE, was independently funded. J.A.N. was funded by a career development award from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK082729-04). P.W.F. was funded by a Distinguished Young Research Award in Medicine from the Swedish Research Council and EXODIAB. Funding to pay the Open Access publication charges for this article was provided by the Swedish Research Council. Cohort-specific funding and acknowledgments follow in the sections below. NR 33 TC 10 Z9 11 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 15 PY 2015 VL 24 IS 16 BP 4728 EP 4738 DI 10.1093/hmg/ddv186 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CR4OU UT WOS:000361315400020 PM 25994509 ER PT J AU Spinler, SA Cziraky, MJ Willey, VJ Tang, FM Maddox, TM Thomas, T Duenas, GG Virani, SS AF Spinler, Sarah A. Cziraky, Mark J. Willey, Vincent J. Tang, Fengming Maddox, Thomas M. Thomas, Tyan Duenas, Gladys G. Virani, Salim S. CA NCDR TI Frequency of Attainment of Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol Goals in Cardiovascular Clinical Practice (from the National Cardiovascular Data Registry PINNACLE Registry) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PANEL-III GUIDELINES; DYSLIPIDEMIA; STATIN; ADULTS; RISK; RECOMMENDATIONS; ACHIEVEMENT; MANAGEMENT AB Studies have found that non-high-density lipoprotein cholesterol (non-HDL-C) is a superior marker for coronary heart disease compared to low-density lipoprotein cholesterol (LDL-C). Little is known about achievement of non-HDL-C goals outside clinical trials. Within a population of 146,064 patients with dyslipidemia in the PINNACLE Registry and a subgroup of 36,188 patients with diabetes mellitus (DM), we examined the proportion of patients and patient characteristics associated with having LDL-C, non-HDL-C, and both LDL-C and non-HDL-C levels at National Cholesterol Education Program goals. LDL-C, non-HDL-C, and both LDL-C and non-HDL-C goals in the overall cohort were achieved by 73%, 73.4%, and 68.9% patients, respectively. Significant predictors of meeting all 3 goals were age, male gender, statin, nonstatin, and combined statin plus nonstatin use. Patients with co-morbidities of hypertension, previous stroke or transient ischemic attack, peripheral arterial disease, myocardial infarction, and smoking were less likely to have LDL-C, non-HDL-C, and both LDL-C and non-HDL-C levels at National Cholesterol Education Program goal. In the overall cohort, patients with DM were less likely to meet non-HDL-C and both LDL-C and non-HDL-C goals. In the subgroup of patients with DM, predictors of meeting lipid goals were similar to the overall cohort. In conclusion, these data suggest contemporary treatment patterns by cardiologists successfully achieve lipid goals in most patients. Younger, female patients and those with atherosclerotic cardiovascular disease and risk factors, such as hypertension and DM, are less likely to achieve goals and may require more careful follow-up after statin initiation. Both LDL-C and non-HDL-C goals are achieved in <70% of patients, suggesting room for improvement if a goal-targeted individualized strategy is adopted. (C) 2015 Elsevier Inc. All rights reserved. C1 [Spinler, Sarah A.; Cziraky, Mark J.; Willey, Vincent J.; Thomas, Tyan; Duenas, Gladys G.] Univ Sci, Philadelphia Coll Pharm, Dept Pharm Practice & Pharm Adm, Philadelphia, PA 19104 USA. [Cziraky, Mark J.; Willey, Vincent J.] HealthCore Inc, Wilmington, DE USA. [Tang, Fengming] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Maddox, Thomas M.] Univ Colorado, Sch Med, Eastern Colorado Healthcare Syst, Denver, CO USA. [Maddox, Thomas M.] CCOR Consortium, Denver, CO USA. [Virani, Salim S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Virani, Salim S.] Baylor Coll Med, Sect Cardiovasc Res, Dept Med, Houston, TX USA. RP Spinler, SA (reprint author), Univ Sci, Philadelphia Coll Pharm, Dept Pharm Practice & Pharm Adm, Philadelphia, PA 19104 USA. EM s.spinle@usciences.edu OI Virani, Salim/0000-0001-9541-6954; Spinler, Sarah/0000-0003-4552-0053 FU Bristol-Myers Squibb; Pfizer Inc. FX PINNACLE Registry is an initiative of the American College of Cardiology Foundation. Bristol-Myers Squibb and Pfizer Inc. are Founding Sponsors of the PINNACLE Registry. NR 17 TC 3 Z9 3 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 AUG 15 PY 2015 VL 116 IS 4 BP 547 EP 553 DI 10.1016/j.amjcard.2015.05.011 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP9ZG UT WOS:000360253800010 PM 26089010 ER PT J AU Mehta, AB Syeda, SN Bajpayee, L Cooke, CR Walkey, AJ Wiener, RS AF Mehta, Anuj B. Syeda, Sohera N. Bajpayee, Lisa Cooke, Colin R. Walkey, Allan J. Wiener, Renda Soylemez TI Trends in Tracheostomy for Mechanically Ventilated Patients in the United States, 1993-2012 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE tracheostomy; epidemiology; United States; mechanical ventilation ID CHRONIC CRITICAL ILLNESS; INTENSIVE-CARE-UNIT; RANDOMIZED CONTROLLED-TRIAL; ACUTE RESPIRATORY-FAILURE; CRITICALLY-ILL PATIENTS; ADMINISTRATIVE DATA; RESOURCE UTILIZATION; ETHNIC-DIFFERENCES; EARLY TRACHEOTOMY; MEDICAL PATIENTS AB Rationale: National trends in tracheostomy for mechanical ventilation (MV) patients are not well characterized. Objectives: To investigate trends in tracheostomy use, timing, and outcomes in the United States. Methods: We calculated estimates of tracheostomy use and outcomes from the National Inpatient Sample from 1993 to 2012. We used hierarchical models to determine factors associated with tracheostomy use among MV patients. Measurements and Main Results: We identified 1,352,432 adults who received tracheostomy from 1993 to 2012 (9.1% of,MV patients). Tracheostomy was more common in surgical patients, men, and racial/ethnic minorities. Age-adjusted incidence of tracheostomy increased by 106%, rising disproportionately to MV use. Among MV patients, tracheostomy rose from 6.9% in 1993 to 9.8% in 2008, and then it declined to 8.7% in 2012 (P < 0.0001). Increases in tracheostomy use were driven by surgical patients (9.5% in 1993; 15.0% in 2012; P < 0.0001), with little change among nonsurgical patients (5.8% in 1993; 5.9% in 2012; P < 0.0001). Over time, tracheostomies were performed earlier (median, 11 d in 1998; 10 d in 2012; P < 0.0001), whereas hospital length of stay declined (median, 39 d in 1993; 26 d in 2012; P < 0.0001), discharges to long-term facilities increased (40.1% vs. 71.9%; P < 0.0001), and hospital mortality declined (38.1% vs. 14.7%; P < 0.0001). Conclusions: Over the past two decades, tracheostomy use rose substantially in the United States until 2008, when use began to decline. The observed dramatic increase in discharge of tracheostomy patients to long-term care facilities may have significant implications for clinical care, healthcare costs, policy, and research. Future studies should include long-term facilities when analyzing outcomes of tracheostomy. C1 [Mehta, Anuj B.; Syeda, Sohera N.; Bajpayee, Lisa; Walkey, Allan J.; Wiener, Renda Soylemez] Boston Univ, Sch Med, Dept Med, Pulm Ctr,Div Pulm & Crit Care Med, Boston, MA 02118 USA. [Syeda, Sohera N.] VA Boston Healthcare Syst, Boston, MA USA. [Cooke, Colin R.] Univ Michigan, Dept Med, Inst Healthcare Policy & Innovat, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Wiener, Renda Soylemez] Edith Nourse Rogers Mem VA Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. RP Mehta, AB (reprint author), 72 East Concord St, Boston, MA 02118 USA. EM anuj.mehta2@bmc.org OI Walkey, Allan/0000-0003-4685-6894; Wiener, Renda/0000-0001-7712-2135 FU National Institutes of Health (NIH) [T32 86308]; Agency for Healthcare and Research Quality [K08HS020672]; NIH NHLBI [K01HL116768]; NIH [K07 CA138772] FX Supported in part by National Institutes of Health (NIH) grant T32 86308 (A.B.M.), Agency for Healthcare and Research Quality grant K08HS020672 (C.R.C.), NIH NHLBI grant K01HL116768 (A.J.W.), and NIH grant K07 CA138772 (R.S.W.). This study was also supported by resources from the VA Boston Healthcare System (S.N.S.) and the Edith Nourse Rogers Memorial VA Hospital (R.S.W.). NR 51 TC 9 Z9 10 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 15 PY 2015 VL 192 IS 4 BP 446 EP 454 DI 10.1164/rccm.201502-0239OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CP9AS UT WOS:000360186700011 PM 25955332 ER PT J AU Mostert, S Lam, CG Njuguna, F Patenaude, AF Kulkarni, K Salaverria, C AF Mostert, Saskia Lam, Catherine G. Njuguna, Festus Patenaude, Andrea F. Kulkarni, Ketan Salaverria, Carmen CA SIOP PODC Global Taskforce Hosp TI Hospital detention practices: statement of a global taskforce SO LANCET LA English DT Letter C1 [Mostert, Saskia] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Lam, Catherine G.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Njuguna, Festus] Moi Teaching & Referral Hosp, Eldoret, Kenya. [Patenaude, Andrea F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kulkarni, Ketan] IWK Hlth Ctr, Halifax, NS, Canada. [Salaverria, Carmen] Natl Childrens Hosp Benjamin Bloom, San Salvador, El Salvador. RP Mostert, S (reprint author), Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. EM s.mostert@vumc.nl RI Lam, Catherine/K-6328-2014 OI Lam, Catherine/0000-0003-1363-5331 NR 5 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD AUG 15 PY 2015 VL 386 IS 9994 BP 649 EP 649 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CP4KA UT WOS:000359849200023 PM 26334151 ER PT J AU Matsuyama, T Tanaka, T Tatsumi, K Daijo, H Kai, S Harada, H Fukuda, K AF Matsuyama, Tomonori Tanaka, Tomoharu Tatsumi, Kenichiro Daijo, Hiroki Kai, Shinichi Harada, Hiroshi Fukuda, Kazuhiko TI Midazolam inhibits the hypoxia-induced up-regulation of erythropoietin in the central nervous system SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Midazolam; Erythropoietin; Hypoxia-inducible factor ID CYTOPLASMIC DYNEIN; INDUCIBLE FACTOR-1; GENE-EXPRESSION; RAT ASTROCYTES; IN-VITRO; RECEPTOR; BRAIN; NEUROPROTECTION; TRAFFICKING; REPERFUSION AB Erythropoietin (EPO), a regulator of red blood cell production, is endogenously expressed in the central nervous system. It is mainly produced by astrocytes under hypoxic conditions and has proven to have neuroprotective and neurotrophic effects. In the present study, we investigated the effect of midazolam on EPO expression in primary cultured astrocytes and the mouse brain. Midazolam was administered to 6-week-old BALB/c male mice under hypoxic conditions and pregnant C57BL/6N mice under normoxic conditions. Primary cultured astrocytes were also treated with midazolam under hypoxic conditions. The expression of [PO mRNA in mice brains and cultured astrocytes was studied. In addition, the expression of hypoxia-inducible factor (HIE), known as the main regulator of EPO, was evaluated. Midazolam significantly reduced the hypoxia-induced up regulation of EPO in BALB/c mice brains and primary cultured astrocytes and suppressed EPO expression in the fetal brain. Miclazolarn did not affect the total amount of HIF proteins but significantly inhibited the nuclear expression of HIF-1 alpha and HIF-2 alpha proteins. These results demonstrated the suppressive effects of midazolam on the hypoxia-induced up -regulation of EPO both in vivo and in vitro. (C) 2015 Elsevier B.V. All rights reserved C1 [Matsuyama, Tomonori; Tanaka, Tomoharu; Tatsumi, Kenichiro; Daijo, Hiroki; Fukuda, Kazuhiko] Kyoto Univ Hosp, Dept Anesthesia, Sakyo Ku, Kyoto 6068507, Japan. [Kai, Shinichi] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Harada, Hiroshi] Kyoto Univ, Grad Sch Med, Dept Radiat Oncol & Image Appl Therapy, Kyoto 6068501, Japan. RP Tanaka, T (reprint author), Kyoto Univ Hosp, Dept Anesthesia, Sakyo Ku, 54 Kawahara Cho, Kyoto 6068507, Japan. EM 665tana@kuhp.kyoto-u.ac.jp FU Japan Society for the Promotion of Science (Tokyo, Japan) [23791703] FX We would like to thank Dr. Kiichi Hirota (Department of Anesthesiology, Kansai Medical University, Hirakata, Japan) for his advice on experimental settings and data analysis. This research received the Grant-in Aid for Scientific Research 23791703 from the Japan Society for the Promotion of Science (Tokyo, Japan). NR 55 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 EI 1879-0712 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 15 PY 2015 VL 761 BP 189 EP 198 DI 10.1016/j.ejphar.2015.05.024 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CO5VT UT WOS:000359227300025 PM 26001375 ER PT J AU Im, M Fried, SI AF Im, Maesoon Fried, Shelley I. TI Indirect activation elicits strong correlations between light and electrical responses in ON but not OFF retinal ganglion cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID RETINITIS-PIGMENTOSA; RECEPTIVE-FIELDS; VISUAL-PERCEPTION; MAMMALIAN RETINA; DEGENERATION RD1; TIGER SALAMANDER; PRIMATE RETINA; STIMULATION; RABBIT; MICE AB To improve the efficacy of microelectronic retinal prosthetics it will be necessary to better understand the response of retinal neurons to electric stimulation. While stimulation that directly activates ganglion cells generally has the lowest threshold, the similarity in responsiveness across cells makes it extremely difficult for such an approach to re-create cell-type specific patterns of neural activity that arise normally in the healthy retina. In contrast, stimulation that activates neurons presynaptic to ganglion cells utilizes at least some of the existing retinal circuitry and therefore is thought to produce neural activity that better matches physiological signalling. Surprisingly, the actual benefit(s) of this approach remain unsubstantiated. Here, we recorded from ganglion cells in the rabbit retinal explant in response to electrical stimuli that activated the network. Targeted cells were first classified into known types via light responses so that the consistency of electrical responses within individual types could be evaluated. Both transient and sustained ON ganglion cells exhibited highly consistent electrical response patterns which were distinct from one another. Further, properties of the response (interspike interval, latency, peak firing rate, and spike count) in a given cell were well correlated to the corresponding properties of the light response for that same cell. Electric responses in OFF ganglion cells formed two groups, distinct from ON groups, and the correlation levels between electric and light responses were much weaker. The closer match in ON pathway responses may help to explain some preferential reporting of bright stimuli during psychophysical testing. C1 [Im, Maesoon; Fried, Shelley I.] Vet Affairs Boston Healthcare Syst, Boston, MA 02130 USA. [Im, Maesoon; Fried, Shelley I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Im, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Thier Res Bldg,Room 415,50 Blossom St, Boston, MA 02114 USA. EM im.maesoon@mgh.harvard.edu OI Im, Maesoon/0000-0003-1152-4398 FU VA Boston Healthcare System [1I01RX000350-01A1]; NIH [R01EY019967, R01EY023651] FX This work was supported by the VA Boston Healthcare System (1I01RX000350-01A1) and by the NIH (R01EY019967, R01EY023651). NR 50 TC 6 Z9 6 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG 15 PY 2015 VL 593 IS 16 BP 3577 EP 3596 DI 10.1113/JP270606 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA CP2UY UT WOS:000359733900014 PM 26033477 ER PT J AU Keane, FK Chen, MH Zhang, DJ Moran, BJ Braccioforte, MH D'Amico, AV AF Keane, Florence K. Chen, Ming-Hui Zhang, Danjie Moran, Brian J. Braccioforte, Michelle H. D'Amico, Anthony V. TI Androgen Deprivation Therapy and the Risk of Death From Prostate Cancer Among Men With Favorable or Unfavorable Intermediate-Risk Disease SO CANCER LA English DT Article DE prostate cancer; intermediate-risk prostate cancer; androgen deprivation therapy; brachytherapy; external-beam radiotherapy; unfavorable intermediate-risk prostate cancer; favorable intermediate-risk prostate cancer ID BEAM RADIATION-THERAPY; RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY; HORMONAL-THERAPY; BRACHYTHERAPY; RADIOTHERAPY; SUPPRESSION; VOLUME; ADENOCARCINOMA; CAPSURE AB BACKGROUND: Radiotherapy (RT), short-course androgen deprivation therapy (ADT), and brachytherapy in various combinations are treatment options for patients with intermediate-risk prostate cancer (PC), but the question of which combination if any is necessary to minimize PC-specific mortality (PCSM) risk in patients with favorable or unfavorable intermediate-risk PC is unknown. The authors assessed PCSM risk after commonly used treatments. METHODS: The cohort consisted of 2510 men with favorable (1902 men; 75.78%) or unfavorable (608 men; 24.22%) intermediate-risk PC who were treated from 1997 to 2013. Treatment included brachytherapy with or without neoadjuvant ADT among men with favorable disease and brachytherapy with neoadjuvant RT or ADT among men with unfavorable disease. Fine and Gray's competing-risks regression model was used to assess whether ADT among men with favorable disease or RT or ADT among men with unfavorable disease decreased PCSM risk after adjusting for treatment propensity score, year of brachytherapy, and PC prognostic factors. RESULTS: After a median follow-up of 7.78 years, 366 deaths (14.58%) were observed, 29 of which (7.92%) were from PC. There was a significant reduction in PCSM risk in men with unfavorable disease who were treated with ADT versus RT (adjusted hazard ratio, 0.34; 95% confidence interval, 0.13-0.91 [P=.03]), but no significant difference in PCSM risk in men with favorable disease who received ADT and brachytherapy versus brachytherapy (adjusted hazard ratio, 0.67; 95% confidence interval, 0.18-2.57 [P=.56]). CONCLUSIONS: Neoadjuvant ADT does not appear to reduce PCSM risk in men undergoing brachytherapy for favorable intermediate-risk PC and should not be considered a standard; however, it appears superior to neoadjuvant RT in men with unfavorable intermediate-risk PC undergoing brachytherapy, making neoadjuvant ADT and brachytherapy a preferred option in these men. (C) 2015 American Cancer Society. C1 [Keane, Florence K.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02215 USA. [Chen, Ming-Hui; Zhang, Danjie] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Moran, Brian J.; Braccioforte, Michelle H.] Prostate Canc Fdn Chicago, Westmont, IL USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Keane, FK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St,ASB1 L2, Boston, MA 02215 USA. EM fkeane@partners.org NR 28 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD AUG 15 PY 2015 VL 121 IS 16 BP 2713 EP 2719 DI 10.1002/cncr.29420 PG 7 WC Oncology SC Oncology GA CO5HO UT WOS:000359190400011 PM 25925789 ER PT J AU El-Jawahri, AR Abel, GA Steensma, DP LeBlanc, TW Fathi, AT Graubert, TA DeAngelo, DJ Wadleigh, M Ballen, KK Foster, JE Attar, EC Amrein, PC Brunner, AM Stone, RM Temel, JS AF El-Jawahri, Areej R. Abel, Gregory A. Steensma, David P. LeBlanc, Thomas W. Fathi, Amir T. Graubert, Timothy A. DeAngelo, Daniel J. Wadleigh, Martha Ballen, Karen K. Foster, Julia E. Attar, Eyal C. Amrein, Philip C. Brunner, Andrew M. Stone, Richard M. Temel, Jennifer S. TI Health Care Utilization and End-of-Life Care for Older Patients With Acute Myeloid Leukemia SO CANCER LA English DT Article DE acute myeloid leukemia; end-of-life care; health care utilization; palliative care ID RANDOMIZED PHASE-III; ELDERLY-PATIENTS; PALLIATIVE CARE; SUPPORTIVE CARE; HEMATOLOGIC MALIGNANCIES; MYELODYSPLASTIC SYNDROME; EUROPEAN ORGANIZATION; MENTAL-HEALTH; QUALITY; CANCER AB BACKGROUND: Health care utilization in older adults (age >= 60 years) with acute myeloid leukemia (AML) has not been well studied. METHODS: We conducted a retrospective analysis of 330 consecutive older patients who were diagnosed with AML between May 1, 2005 and December 23, 2011, at 2 hospitals in Boston to examine their health care utilization and end-of-life care. Using multivariable logistic and linear regression models adjusting for covariates, we also compared health care utilization between patients who received intensive induction chemotherapy (n=197; cytarabine/ anthracycline combination) versus nonintensive chemotherapy (n=133; single-agent therapy). RESULTS: The median number of hospitalizations for the entire cohort was 4.2 (range, 1-18 hospitalizations). Patients who died spent a mean of 28.3% of their life after diagnosis in the hospital and 13.8% of their life attending outpatient clinic appointments. Although the majority of patients (87.9%) died during the 2-year follow-up period, a minority received palliative care (16.2%) or hospice (23.1%) services. Within 30 days of death, 84.5% of patients were hospitalized, and 61% died in the hospital. Among the patients who died, those who received intensive induction therapy (vs nonintensive therapy) spent 30% more of their life after diagnosis in the hospital (P<.0001) and were less likely to receive hospice services (odds ratio, 0.45; P=.05). CONCLUSIONS: The current findings highlight the intensity of health care utilization among older patients with AML, regardless of treatment modality. Despite the poor prognosis, palliative care and hospice services are rarely used. Future work should study novel health care delivery models to optimize care throughout the course of illness and at the end of life. (C) 2015 American Cancer Society. C1 [El-Jawahri, Areej R.; Fathi, Amir T.; Graubert, Timothy A.; Ballen, Karen K.; Foster, Julia E.; Attar, Eyal C.; Amrein, Philip C.; Brunner, Andrew M.; Temel, Jennifer S.] Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. [El-Jawahri, Areej R.; Abel, Gregory A.; Steensma, David P.; Fathi, Amir T.; Graubert, Timothy A.; DeAngelo, Daniel J.; Wadleigh, Martha; Ballen, Karen K.; Foster, Julia E.; Attar, Eyal C.; Amrein, Philip C.; Brunner, Andrew M.; Stone, Richard M.; Temel, Jennifer S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Abel, Gregory A.; Steensma, David P.; DeAngelo, Daniel J.; Wadleigh, Martha; Stone, Richard M.] Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. [LeBlanc, Thomas W.] Duke Univ, Sch Med, Div Hematol Malignancies & Cellular Therapy, Durham, NC USA. RP El-Jawahri, AR (reprint author), Dept Hematol, Oncol Bone Marrow Transplantat Program, 55 Fruit St, Boston, MA 02114 USA. EM ael-jawahri@partners.org FU National Cancer Institute Federal Share Program [K12]; National Palliative Care Research Center (NPCRC CDA); NPCRC; [K24 CA 181253] FX Dr. El-Jawahri is supported by funds from the National Cancer Institute Federal Share Program (K12) and the National Palliative Care Research Center (NPCRC CDA). Dr. LeBlanc is supported by funds from the NPCRC. Dr. Temel is supported by funds from K24 CA 181253. NR 28 TC 8 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD AUG 15 PY 2015 VL 121 IS 16 BP 2840 EP 2848 DI 10.1002/cncr.29430 PG 9 WC Oncology SC Oncology GA CO5HO UT WOS:000359190400026 PM 25926135 ER PT J AU Goetz, MB Hoang, T Kan, VL Rimland, D Rodriguez-Barradas, MC Asch, SM AF Goetz, Matthew Bidwell Hoang, Tuyen Kan, Virginia L. Rimland, David Rodriguez-Barradas, Maria C. Asch, Steven M. TI Rates and Predictors of Newly Diagnosed HIV Infection Among Veterans Receiving Routine Once-Per-Lifetime HIV Testing in the Veterans Health Administration SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; COST-EFFECTIVENESS; CARE SETTINGS; PERSONS AWARE; POPULATION; AFFAIRS; OLDER; RISK AB Objective: To determine predictors and variations in the rate of newly diagnosed HIV infection among persons who underwent routine (ie, non-risk based) rather than risk-based HIV testing in Veterans Health Administration (VHA) facilities. Methods: Retrospective observational study of the HIV infection new rates during the period when VHA policy called for routine (2009-2012) versus risk-based (2006-2009) HIV testing. Source data for testing results at 18 VHA facilities were obtained from the VHA National Corporate Data Warehouse. Results: New HIV diagnoses were established in 0.14% (95% confidence interval (CI): 0.12 to 0.46) of the 210,957 patients tested in the routine testing period versus 0.46% (95% CI: 0.42 to 1.29) of the 89,652 patients tested in the risk-based testing period. Among persons aged 65-74 years and 75 years or older, the new diagnosis rates were 0.07% (95% CI: 0.04 to 0.09) and 0.02% (95% CI: 0.00 to 0.03), respectively, and thus less than the generally accepted cost-effective threshold of 0.10%. Among African Americans, the upper bound of the 95% CI of the crude rate of new diagnoses during the routine-testing period was greater than 0.1% across all age strata. When assessed by year of testing, the adjusted rates of new diagnoses fell from 0.20% in 2010 to 0.10% in 2012. Conclusions: Routine HIV testing is cost-effective among persons younger than 65 years. Among older patients, risk-based testing may be a more efficient and cost-effective approach. This will be increasingly relevant if rates of new HIV diagnoses in persons undergoing routine testing continue to decrease. C1 [Goetz, Matthew Bidwell; Hoang, Tuyen] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell; Hoang, Tuyen] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kan, Virginia L.] Washington DC VA Med Ctr, Washington, DC USA. [Kan, Virginia L.] George Washington Univ, Sch Med, Washington, DC USA. [Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. [Asch, Steven M.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Asch, Steven M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. RP Goetz, MB (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM matthew.goetz@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU Veterans Health Administration, Health Services Research & Development Service [RRP 12-220] FX Supported by Veterans Health Administration, Health Services Research & Development Service (RRP 12-220). NR 46 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 15 PY 2015 VL 69 IS 5 BP 544 EP 550 DI 10.1097/QAI.0000000000000653 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CN1VP UT WOS:000358208800005 PM 25886931 ER PT J AU Sabin, LL DeSilva, MB Gill, CJ Zhong, L Vian, T Xie, WB Cheng, F Xu, KY Lan, GH Haberer, JE Bangsberg, DR Li, YZ Lu, HY Gifford, AL AF Sabin, Lora L. DeSilva, Mary Bachman Gill, Christopher J. Zhong, Li Vian, Taryn Xie, Wubin Cheng, Feng Xu, Keyi Lan, Guanghua Haberer, Jessica E. Bangsberg, David R. Li, Yongzhen Lu, Hongyan Gifford, Allen L. TI Improving Adherence to Antiretroviral Therapy With Triggered Real-time Text Message Reminders: The China Adherence Through Technology Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HIV-INFECTED PATIENTS; SUB-SAHARAN AFRICA; MEDICATION ADHERENCE; RESISTANT HIV-1; VIRAL LOAD; FOLLOW-UP; INTERVENTIONS; HIV/AIDS; TRANSMISSION AB Background: Real-time adherence monitoring is now possible through medication storage devices equipped with cellular technology. We assessed the effect of triggered cell phone reminders and counseling using objective adherence data on antiretroviral therapy (ART) adherence among Chinese HIV-infected patients. Methods: We provided ART patients in Nanning, China, with a medication device (Wisepill) to monitor their ART adherence electronically. After 3 months, we randomized subjects within optimal (>= 95%) and suboptimal (<95%) adherence strata to intervention vs. control arms. In months 4-9, intervention subjects received individualized reminders triggered by late dose taking (no device opening by 30 minutes past dose time) and counseling using device-generated data. Controls received no reminders or data-informed counseling. We compared postintervention proportions achieving optimal adherence, mean adherence, and clinical outcomes. Results: Of 120 subjects enrolled, 116 (96.7%) completed the trial. Preintervention optimal adherence was similar in intervention vs. control arms (63.5% vs. 58.9%, respectively; P = 0.60). In the last intervention month, 87.3% vs. 51.8% achieved optimal adherence [risk ratio (RR): 1.7, 95% confidence interval (CI): 1.3 to 2.2] and mean adherence was 96.2% vs. 89.1% (P = 0.003). Among preintervention suboptimal adherers, 78.3% vs. 33.3% (RR: 2.4, CI: 1.2 to 4.5) achieved optimal adherence and mean adherence was 93.3% vs. 84.7% (P = 0.039). Proportions were 92.5% and 62.9% among optimal adherers, respectively (RR: 1.5, CI: 1.1 to 1.9) and mean adherence was 97.8% vs. 91.7% (P = 0.028). Postintervention clinical outcomes were not significant. Conclusions: Real-time reminders significantly improved ART adherence in this population. This approach seems promising for managing HIV and other chronic diseases and warrants further investigation and adaptation in other settings. C1 [Sabin, Lora L.; DeSilva, Mary Bachman; Gill, Christopher J.; Vian, Taryn] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02118 USA. [Sabin, Lora L.; DeSilva, Mary Bachman; Gill, Christopher J.; Vian, Taryn] Boston Univ, Dept Global Hlth, Sch Publ Hlth, Boston, MA 02118 USA. [Zhong, Li; Xie, Wubin] FHI 360, Beijing, Peoples R China. [Cheng, Feng] Tsinghua Univ, Res Ctr Publ Hlth TPHRC, Sch Med, Beijing 100084, Peoples R China. [Xu, Keyi] WHO Collaborating Ctr Comprehens Management HIV T, Ditan Hosp, Beijing, Peoples R China. [Lan, Guanghua; Li, Yongzhen; Lu, Hongyan] Guangxi Ctr Dis Control & Prevent, Div Aids, Nanning, Peoples R China. [Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Gifford, Allen L.] Boston Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA 02118 USA. [Gifford, Allen L.] Edith Nourse Rogers Mem VA Hosp, Bedford, MA USA. RP Sabin, LL (reprint author), Boston Univ, Dept Global Hlth, Sch Publ Hlth, Crosstown Ctr, 801 Massachusetts Ave, Boston, MA 02118 USA. EM lsabin@bu.edu RI Emchi, Karma/Q-1952-2016; OI Vian, Taryn/0000-0002-6968-7002 FU US CDCGAP office; National Center for AIDS/STD Control and Prevention (NCAIDS); Chinese Center for Disease Control and Prevention, in Beijing FX The authors thank the late Richard Denisco and Dr. Tang Zhirong, Deirdre Pierotti and Sherley Brice at Boston University, former program manager Bram Brooks, Katherine Semrau of Harvard Medical School and Brigham and Women's Hospital, and Mark Harrold and Evan Hecht. The authors appreciate the support of experts at the US CDCGAP office and the National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention, in Beijing. NR 54 TC 16 Z9 16 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 15 PY 2015 VL 69 IS 5 BP 551 EP 559 DI 10.1097/QAI.0000000000000651 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CN1VP UT WOS:000358208800006 PM 25886927 ER PT J AU Dougherty, DD Rezai, AR Carpenter, LL Howland, RH Bhati, MT O'Reardon, JP Eskandar, EN Baltuch, GH Machado, AD Kondziolka, D Cusin, C Evans, KC Price, LH Jacobs, K Pandya, M Denko, T Tyrka, AR Brelje, T Deckersbach, T Kubu, C Malone, DA AF Dougherty, Darin D. Rezai, Ali R. Carpenter, Linda L. Howland, Robert H. Bhati, Mahendra T. O'Reardon, John P. Eskandar, Emad N. Baltuch, Gordon H. Machado, Andre D. Kondziolka, Douglas Cusin, Cristina Evans, Karleyton C. Price, Lawrence H. Jacobs, Karen Pandya, Mayur Denko, Timothey Tyrka, Audrey R. Brelje, Tim Deckersbach, Thilo Kubu, Cynthia Malone, Donald A., Jr. TI A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Deep brain stimulation; DBS; Treatment resistant depression; TRD; Major depression; Ventral capsule/ventral striatum ID MAJOR DEPRESSION; DISORDER AB BACKGROUND: Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published. METHODS: Thirty patients with TRD participated in a sham-controlled trial of DBS at the ventral capsule/ventral striatum target for TRD. Patients were randomized to active versus sham DBS treatment in a blinded fashion for 16 weeks, followed by an open-label continuation phase. The primary outcome measure was response, defined as a 50% or greater improvement on the Montgomery-Asberg Depression Rating Scale from baseline. RESULTS: There was no significant difference in response rates between the active (3 of 15 subjects; 20%) and control (2 of 14 subjects; 14.3%) treatment arms and no significant difference between change in Montgomery-Asberg Depression Rating Scale scores as a continuous measure upon completion of the 16-week controlled phase of the trial. The response rates at 12, 18, and 24 months during the open-label continuation phase were 20%, 26.7%, and 23.3%, respectively. CONCLUSION: The results of this first randomized controlled study of DBS for the treatment of TRD did not demonstrate a significant difference in response rates between the active and control groups at the end of the 16-week controlled phase. However, a range of 20% to 26.7% of patients did achieve response at any time during the open-label continuation phase. Future studies, perhaps utilizing alternative study designs and stimulation parameters, are needed. C1 [Dougherty, Darin D.; Cusin, Cristina; Evans, Karleyton C.; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Rezai, Ali R.; Jacobs, Karen; Pandya, Mayur; Kubu, Cynthia; Malone, Donald A., Jr.] Cleveland Clin, Dept Psychiat & Psychol, Cleveland, OH 44106 USA. [Carpenter, Linda L.; Price, Lawrence H.; Tyrka, Audrey R.] Brown Univ, Butler Hosp, Alpert Med Sch, Providence, RI 02912 USA. [Howland, Robert H.; Deckersbach, Thilo] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. [Bhati, Mahendra T.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. [Baltuch, Gordon H.] Univ Penn, Perelman Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. [Machado, Andre D.] Cleveland Clin, Ctr Neurol Restorat, Cleveland, OH 44106 USA. [Kondziolka, Douglas] NYU, Dept Neurosurg, Langone Med Ctr, New York, NY 10016 USA. [O'Reardon, John P.] Univ Med & Dent, New Jersey Sch Osteopath, Dept Psychiat, Stratford, NJ USA. [Brelje, Tim] Medtronic Inc, Minneapolis, MN USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,CNY2612, Charlestown, MA 02129 USA. EM ddougherty@partners.org RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 FU Medtronic, Inc.; Eli Lilly; Cyberonics; Roche; Neuronetics Inc.; NeoSync Inc.; Cervel Neurotech Inc.; National Institute of Mental Health (NIMH); National Alliance for Research on Schizophrenia and Depression; NeoSync; Corcept; Takeda; Otsuka; Shire; American Psychiatric Association; Defense Advanced Research Projects Agency; Medtronic; Pfizer; Neuronetics; Cervel Neurotech; NIH; Stanley Medical Research Institute; AstraZeneca; BMS; CeNeRX Biopharma; Sanofi; Magstim; NIMH; Tourette Syndrome Association; International OCD Foundation; Tufts University; Depressive and Bipolar Disorder Alternative Treatment Foundation; Massachusetts General Hospital Psychiatry Academy; BrainCells Inc.; Clintara, LLC; Systems Research and Applications Corporation; Boston University; Catalan Agency for Health Technology Assessment and Research; National Association of Social Workers Massachusetts; Massachusetts Medical Society; National Institute on Drug Abuse; Oxford University Press; DARPA; National Institute on Aging; Agency for Healthcare Research and Quality; Patient-Centered Outcomes Research Institute; Janssen Pharmaceuticals; Forest Research Institute; Shire Development Inc.; Northstar; National Institutes of Health (NIH) NeoSync; Butler Hospital FX This study was funded by Medtronic, Inc. We acknowledge Amanda Arulpragasam for assistance with manuscript preparation. Ms. Arulpragasam is the clinical research coordinator for the Reclaim Deep Brain Stimulation Clinical Study for Treatment-Resistant Depression at the Massachusetts General Hospital. Her knowledge and familiarity with the trial allowed her to contribute thoughtfully to manuscript preparation, edits, and revisions.; All authors have received research support from Medtronic, Inc., the sponsor company of the clinical trial reported in this manuscript. In the last two years, Dr. Dougherty has received honoraria from Reed Elsevier and Medtronic. He has also served as a consultant to Medtronic and received grant/research support from Eli Lilly, Cyberonics, and Roche. Dr. Rezai is on the Board of Directors for Autonomic Technologies and is also an Equity holder. Dr. Carpenter has received research support from Neuronetics Inc., NeoSync Inc., and Cervel Neurotech Inc. through clinical trials with Butler Hospital. Dr. Carpenter also reports a consulting relationship with Magstim. Dr. Howland has received grant/research support from National Institute of Mental Health (NIMH), National Alliance for Research on Schizophrenia and Depression, Cyberonics, NeoSync, Corcept, Takeda, Otsuka, and Shire. Dr. Bhati has received research funding from the American Psychiatric Association, NeoSync, and Cyberonics. Dr. Baltuch has received support from Defense Advanced Research Projects Agency. Dr. Machado is a consultant to Functional Neuromodulation and Spinal Modulation. He has distribution rights related to Intellectual Property from Enspire, Autonomic Technologies, Inc. and Cardionomics. He also has fellowship support from Medtronic. Dr. Evans has received grant support from Cyberonics and Pfizer. He is currently an employee and shareholder of Biogen Idec. Dr. Price has served on an advisory panel for Abbott. Additionally, he has served as a consultant to Wiley, Springer, Qatar National Research Fund, and Abbott and has received grant/research support from Neuronetics, National Institutes of Health (NIH) NeoSync, and Cervel Neurotech. Dr. Jacobs has received honoraria from Takeda and the Lundbeck Speaker Bureau. Dr. Pandya has received honoraria from the Lundbeck Speaker Bureau. Dr. Tyrka has received grant/research support from Neuronetics, NIH, NeoSync, and Cervel Neurotech. Dr O'Reardon has served as a consultant to IC Axon, Lilly, and Neuronetics. He has also received grant/research support from NeoSync, Stanley Medical Research Institute, AstraZeneca, BMS, CeNeRX Biopharma, Cyberonics, Neuronetics, Pfizer, Sanofi, and Magstim. Mr. Brelje is an employee and shareholder of Medtronic. Dr. Deckersbach's research has been funded by NIMH, National Alliance for Research on Schizophrenia and Depression, Tourette Syndrome Association, International OCD Foundation, Tufts University and Depressive and Bipolar Disorder Alternative Treatment Foundation. He has received honoraria, consultation fees and/or royalties from the Massachusetts General Hospital Psychiatry Academy, BrainCells Inc., Clintara, LLC, Systems Research and Applications Corporation, Boston University, the Catalan Agency for Health Technology Assessment and Research, the National Association of Social Workers Massachusetts, the Massachusetts Medical Society, Tufts University, National Institute on Drug Abuse, and Oxford University Press. He has also participated in research funded by DARPA, NIH, NIMH, National Institute on Aging, Agency for Healthcare Research and Quality, Patient-Centered Outcomes Research Institute, Janssen Pharmaceuticals, The Forest Research Institute, Shire Development Inc., Cyberonics, Northstar, and Takeda. Dr. Kubu has received research support from the NIH. Dr. Malone has served on an advisory board for Astra Zeneca. He has also received grant/research support from the NIH. All other authors report no additional financial interests or potential conflicts of interests. NR 21 TC 52 Z9 53 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 2015 VL 78 IS 4 BP 240 EP 248 DI 10.1016/j.biopsych.2014.11.023 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CN0DS UT WOS:000358084200010 PM 25726497 ER PT J AU Bogoch, II Siemieniuk, RAC Andrews, JR Scully, EP Mayer, KH Bell, CM Zachary, KC Yawetz, S AF Bogoch, Isaac I. Siemieniuk, Reed A. C. Andrews, Jason R. Scully, Eileen P. Mayer, Kenneth H. Bell, Chaim M. Zachary, Kimon C. Yawetz, Sigal TI Changes to Initial Postexposure Prophylaxis Regimens Between the Emergency Department and Clinic SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter C1 [Bogoch, Isaac I.] Univ Hlth Network, Div Infect Dis, Toronto, ON, Canada. [Bogoch, Isaac I.; Siemieniuk, Reed A. C.; Bell, Chaim M.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Bogoch, Isaac I.; Bell, Chaim M.] Univ Hlth Network, Mt Sinai Hosp, Div Gen Internal Med, Toronto, ON, Canada. [Andrews, Jason R.] Stanford Univ, Sch Med, Div Infect Dis & Geog Med, Stanford, CA USA. [Scully, Eileen P.; Yawetz, Sigal] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Scully, Eileen P.; Mayer, Kenneth H.; Zachary, Kimon C.; Yawetz, Sigal] Harvard Univ, Sch Med, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Zachary, Kimon C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Bogoch, II (reprint author), Univ Hlth Network, Div Infect Dis, Toronto, ON, Canada. RI Bell, Chaim/C-4611-2015 OI Bell, Chaim/0000-0002-3778-9469 NR 0 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 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 15 PY 2015 VL 69 IS 5 BP e182 EP e184 DI 10.1097/QAI.0000000000000680 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CN1VS UT WOS:000358209100005 PM 25967272 ER PT J AU Reijmer, YD Schultz, AP Leemans, A O'Sullivan, MJ Gurol, ME Sperling, R Greenberg, SM Viswanathan, A Hedden, T AF Reijmer, Y. D. Schultz, A. P. Leemans, A. O'Sullivan, M. J. Gurol, M. E. Sperling, R. Greenberg, S. M. Viswanathan, A. Hedden, T. TI Decoupling of structural and functional brain connectivity in older adults with white matter hyperintensities SO NEUROIMAGE LA English DT Article DE Functional MRI; Diffusion tensor imaging; Connectivity; Cognition; Aging; White matter hyperintensities ID DEFAULT-MODE NETWORK; MILD COGNITIVE IMPAIRMENT; SPHERICAL DECONVOLUTION; SUBJECT MOTION; DIFFUSION MRI; MICROSTRUCTURAL INTEGRITY; ALZHEIMERS-DISEASE; STATE; AGE; CINGULUM AB Age-related impairments in the default network (DN) have been related to disruptions in connecting white matter tracts. We hypothesized that the local correlation between DN structural and functional connectivity is negatively affected in the presence of global white matter injury. In 125 clinically normal older adults, we tested whether the relationship between structural connectivity (via diffusion imaging tractography) and functional connectivity (via resting-state functional MRI) of the posterior cingulate cortex (PCC) and medial prefrontal frontal cortex (MPFC) of the DN was altered in the presence of white matter hyperintensities (WMH). A significant correlation was observed between microstructural properties of the cingulum bundle and MPFC-PCC functional connectivity in individuals with low WMH load, but not with high WMH load. No correlation was observed between PCC-MPFC functional connectivity and microstructure of the inferior longitudinal fasciculus, a tract not passing through the PCC or MPFC. Decoupling of connectivity, measured as the absolute difference between structural and functional connectivity, in the high WMH group was related to poorer executive functioning and memory performance. These results suggest that such decoupling may reflect reorganization of functional networks in response to global white matter pathology and may provide an early marker of clinically relevant network alterations. (C) 2015 Elsevier Inc. All rights reserved. C1 [Reijmer, Y. D.; Gurol, M. E.; Sperling, R.; Greenberg, S. M.; Viswanathan, A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schultz, A. P.; Sperling, R.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hedden, T.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schultz, A. P.; Sperling, R.; Hedden, T.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Leemans, A.] Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands. [O'Sullivan, M. J.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London WC2R 2LS, England. [Sperling, R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Reijmer, YD (reprint author), JP Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM yreijmer@mgh.harvard.edu RI Leemans, Alexander/A-1784-2011; OI Reijmer, Yael/0000-0002-2566-7122 FU National Institute on Aging grants [P01 AG036694, P50 AG005134, K01 AG040197]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health; NIH Shared Instrumentation Grant Programand/or High-End Instrumentation Grant Program; VIDI Grant from Netherlands Organisation for Scientific Research (NWO) [639.072.411]; [S10 RR023401]; [S10 RR023043] FX Funding was provided by the National Institute on Aging grants P01 AG036694, P50 AG005134, and K01 AG040197. 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, P41 EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Programand/or High-End Instrumentation Grant Program; specifically, grant numbers S10 RR023401 and S10 RR023043. The research of A.L. is supported by VIDI Grant 639.072.411 from the Netherlands Organisation for Scientific Research (NWO). NR 54 TC 5 Z9 5 U1 2 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD AUG 15 PY 2015 VL 117 BP 222 EP 229 DI 10.1016/j.neuroimage.2015.05.054 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CM9QX UT WOS:000358045100020 PM 26025290 ER PT J AU Riedel, MC Ray, KL Dick, AS Sutherland, MT Hernandez, Z Fox, PM Eickhoff, SB Fox, PT Laird, AR AF Riedel, Michael C. Ray, Kimberly L. Dick, Anthony S. Sutherland, Matthew T. Hernandez, Zachary Fox, P. Mickle Eickhoff, Simon B. Fox, Peter T. Laird, Angela R. TI Meta-analytic connectivity and behavioral parcellation of the human cerebellum SO NEUROIMAGE LA English DT Article DE Cerebellum; Meta-analysis; Co-activations; BrainMap; Meta-analytic connectivity modeling; MACM; Functional connectivity; Neuroinformatics ID INTRINSIC FUNCTIONAL CONNECTIVITY; COGNITIVE-AFFECTIVE SYNDROME; VERBAL WORKING-MEMORY; BASAL GANGLIA; NEUROIMAGING DATA; INTERNAL-MODELS; MOTOR CORTEX; CORTICAL NETWORKS; ACTIVATION; AREAS AB The cerebellum historically has been thought to mediate motor and sensory signals between the body and cerebral cortex, yet cerebellar lesions are also associated with altered cognitive behavioral performance. Neuroimaging evidence indicates that the cerebellum contributes to a wide range of cognitive, perceptual, and motor functions. Here, we used the BrainMap database to investigate whole-brainco-activation patterns between cerebellar structures and regions of the cerebral cortex, as well as associations with behavioral tasks. Hierarchical clustering was performed to meta-analytically identify cerebellar structures with similar cortical co-activation, and independently, with similar correlations to specific behavioral tasks. Strong correspondences were observed in these separate but parallel analyses of meta-analytic connectivity and behavioral metadata. We recovered differential zones of cerebellar co-activation that are reflected across the literature. Furthermore, the behaviors and tasks associated with the different cerebellar zones provide insight into the specialized function of the cerebellum, relating to high-order cognition, emotion, perception, interoception, and action. Taken together, these task-basedmeta-analytic results implicate distinct zones of the cerebellum as critically involved in the monitoring and mediation of psychological responses to internal and external stimuli. Published by Elsevier Inc. C1 [Riedel, Michael C.; Fox, P. Mickle] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Ray, Kimberly L.] Univ Calif Davis, Imaging Res Ctr, Sacramento, CA 95817 USA. [Dick, Anthony S.; Sutherland, Matthew T.] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA. [Hernandez, Zachary] Univ Houston, Dept Elect & Comp Engn, Houston, TX USA. [Eickhoff, Simon B.] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany. [Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Laird, Angela R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA. RP Laird, AR (reprint author), Florida Int Univ, Dept Phys, Modesto Maidique Campus,AHC 4 310,11200 SW 8th St, Miami, FL 33199 USA. EM alaird@fiu.edu RI Eickhoff, Simon/K-2061-2013; OI Eickhoff, Simon/0000-0001-6363-2759; Ray, Kimberly/0000-0003-1302-2834 FU National Institute of Mental Health [R01MH084812, R01-MH074457, R56-MH097870]; National Institute of Drug Abuse [K01-DA037819] FX This study was supported by awards from the National Institute of Mental Health(R01MH084812, R01-MH074457, R56-MH097870) and the National Institute of Drug Abuse(K01-DA037819). NR 117 TC 8 Z9 9 U1 0 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 AUG 15 PY 2015 VL 117 BP 327 EP 342 DI 10.1016/j.neuroimage.2015.05.008 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CM9QX UT WOS:000358045100031 PM 25998956 ER PT J AU Lim, SM Xie, T Westover, KD Ficarro, SB Tae, HS Gurbani, D Sim, T Marto, JA Janne, PA Crews, CM Gray, NS AF Lim, Sang Min Xie, Ting Westover, Kenneth D. Ficarro, Scott B. Tae, Hyun Seop Gurbani, Deepak Sim, Taebo Marto, Jarrod A. Jaenne, Pasi A. Crews, Craig M. Gray, Nathanael S. TI Development of small molecules targeting the pseudokinase Her3 SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Her3; Pseudokinase; Hydrophobic tagging; Cancer; Pyrazolopyrimidine ID TYROSINE KINASE; EXTENDED 5-SUBSTITUENT; SELECTIVE INHIBITORS; LUNG-CANCER; PROTEIN; POTENT; DOMAIN; ERBB3; DEGRADATION; DISCOVERY AB Her3 is a member of the human epidermal growth factor receptor (EGFR) tyrosine kinase family, and it is often either overexpressed or deregulated in many types of human cancer. Her3 has not been the subject of small-molecule inhibitor development because it is a pseudokinase and does not possess appreciable kinase activity. We recently reported on the development of the first selective irreversible Her3 ligand (TX1-85-1) that forms a covalent bond with cysteine 721 which is unique to Her3 among all kinases. We also developed a bi-functional compound (TX2-121-1) containing a hydrophobic adamantane moiety and the same warhead of TX1-85-1 that is capable of inhibiting Her3-dependent signaling and growth. Here we report on the structure-based medicinal chemistry effort that resulted in the discovery of these two compounds. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Lim, Sang Min; Xie, Ting; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Lim, Sang Min; Xie, Ting; Ficarro, Scott B.; Marto, Jarrod A.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lim, Sang Min; Xie, Ting] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Westover, Kenneth D.; Gurbani, Deepak] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Westover, Kenneth D.; Gurbani, Deepak] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Tae, Hyun Seop; Crews, Craig M.] Yale Univ, Dept Chem, Dept Pharmacol, New Haven, CT 06511 USA. [Tae, Hyun Seop; Crews, Craig M.] Yale Univ, Dept Mol Cellular & Dev, New Haven, CT 06511 USA. [Sim, Taebo] Korea Inst Sci & Technol, Chem Kinom Res Ctr, Seoul 136791, South Korea. [Sim, Taebo] KU KIST Grad Sch Converging Sci & Technol, Seoul 136713, South Korea. [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Gray, NS (reprint author), Dana Farber Canc Inst, Longwood Ctr, Room 2209,360 Longwood Ave, Boston, MA 02215 USA. EM Nathanael_Gray@dfci.harvard.edu FU Dana Farber Cancer Institute Lander Fellowship; Claudia Adams Barr Program Award; US National Institutes of Health (NIH) [AI084140]; Cancer Prevention Research Institute of Texas [R1207]; creative/challenging research program of National Research Foundation of Korea [NRF-2011-0028676]; NIH [P01 CA154303] FX This work is supported by the Dana Farber Cancer Institute Lander Fellowship, Claudia Adams Barr Program Award, US National Institutes of Health (NIH) Grant AI084140, Cancer Prevention Research Institute of Texas Grant R1207, creative/challenging research program of National Research Foundation of Korea NRF-2011-0028676, and NIH Grant P01 CA154303. NR 33 TC 4 Z9 4 U1 6 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 15 PY 2015 VL 25 IS 16 BP 3382 EP 3389 DI 10.1016/j.bmcl.2015.04.103 PG 8 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA CM3HF UT WOS:000357572000062 PM 26094118 ER PT J AU Hill, DE Holland, JP AF Hill, David E. Holland, Jason P. TI Computational studies on hypervalent iodonium(III) compounds as activated precursors for F-18 radiofluorination of electron-rich arenes SO COMPUTATIONAL AND THEORETICAL CHEMISTRY LA English DT Article DE Fluoroarene; Iodonium(III); Density functional theory; Fluorination; Hammett plots; Transition state theory ID DENSITY-FUNCTIONAL THERMOCHEMISTRY; GENERALIZED GRADIENT APPROXIMATION; UNSYMMETRICAL DIARYLIODONIUM SALTS; EXCHANGE-CORRELATION FUNCTIONALS; POSITRON-EMISSION-TOMOGRAPHY; CU-CATALYZED FLUORINATION; CORRELATION-ENERGY; AB-INITIO; OXIDATIVE FLUORINATION; EXTRUSION REACTIONS AB Fluorination of deactivated and non-activated electron-rich arenes via nucleophilic aromatic substitution (SNAr) reactions represents a major challenge in medicinal and radiochemistry. In efforts to activate electron-rich arenes for facile synthesis of fluoroarenes, a wide range of reagents have been developed. In particular, aryliodonium(III) species (salts and ylides) show promise as reagents for synthesising F-18-radiolabelled molecules for use in positron emission tomography (PET). However, in fluorination reactions involving a reductive elimination mechanism, aryliodonium(III) reagents present two competing pathways that lead to product (via transition state I (TS1)) or by-product (TS2) formation. Here, we present detailed computational studies using Density Functional Theory (DFT) methods on the relatively stability of these competing transition states and present an analysis based on transition state theory that allows prediction of chemoselectivity in aryliodonium(III) fluorination reactions. The methods developed indicate that the calculated difference in free energy (Delta Delta G) and the calculated equilibrium constant (InK) between the two transition states are chemically accurate molecular descriptors of chemoselectivity in aryliodonium(III) fluorination. It is anticipated that the tools developed here will aid design of the next generation of reagents with increased chemoselectivity for fluorination and radiofluorination of electron-rich arenes. (C) 2015 Elsevier B.V. All rights reserved. C1 [Hill, David E.] Northeastern Univ, Dept Chem, Boston, MA 02115 USA. [Holland, Jason P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging,Dept Radiol, Boston, MA 02114 USA. [Holland, Jason P.] German Canc Consortium DKTK, Heidelberg, Germany. [Holland, Jason P.] Univ Hosp Freiburg, Dept Nucl Med, D-79106 Freiburg, Germany. [Holland, Jason P.] German Canc Res Ctr, Heidelberg, Germany. RP Holland, JP (reprint author), Univ Hosp Freiburg, Dept Nucl Med, Hugestetterstr 55, D-79106 Freiburg, Germany. EM j.holland@dkfz-heidelberg.de FU Australian National Science and Technology Organisation (ANSTO, Sydney); Department of Nuclear Medicine, University Hospital Freiburg; German Cancer Consortium (DKTK); German Cancer Research Center (DKFZ) FX We thank Dr. T. Lee Collier, Dr. Huan Steven Liang, Dr. Benjamin Rotstein, Dr. Nickeisha Stephenson and Dr. Neil Vasdev for helpful discussions. We thank Jon Patteson for assistance with calculations. We are grateful to the staff at the Massachusetts Green High Performance Computing Center (MGHPCC, Holyoke, MA, USA) and the Northeastern University Information Technology Service and Research Computing (Boston, USA; http://www.north-eastern.edu/rc) for technical support and access to the Discovery Cluster. We are grateful to Dr. Rein U. Kirss (Northeastern University) for supporting access to the MGHPCC (DEH). We thank Dr. Ivan Greguric and the Australian National Science and Technology Organisation (ANSTO, Sydney) for providing financial support (JPH). JPH also thanks Prof. Philipp Meyer and Prof. Helmut Maecke at the Department of Nuclear Medicine, University Hospital Freiburg, the German Cancer Consortium (DKTK), and the German Cancer Research Center (DKFZ) for generous financial support. NR 89 TC 6 Z9 6 U1 5 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2210-271X EI 1872-7999 J9 COMPUT THEOR CHEM JI Comput. Theor. Chem. PD AUG 15 PY 2015 VL 1066 BP 34 EP 46 DI 10.1016/j.comptc.2015.05.012 PG 13 WC Chemistry, Physical SC Chemistry GA CM5TM UT WOS:000357751700006 ER PT J AU Chung, TKH Van Hummelen, P Chan, PKS Cheung, TH Yim, SF Yu, MY Ducar, MD Thorner, AR MacConaill, LE Doran, G Pedamallu, CS Ojesina, AI Wong, RRY Wang, VW Freeman, SS Lau, TS Kwong, J Chan, LKY Fromer, M May, T Worley, MJ Esselen, KM Elias, KM Lawrence, M Getz, G Smith, DI Crum, CP Meyerson, M Berkowitz, RS Wong, YF AF Chung, Tony K. H. Van Hummelen, Paul Chan, Paul K. S. Cheung, Tak Hong Yim, So Fan Yu, Mei Y. Ducar, Matthew D. Thorner, Aaron R. MacConaill, Laura E. Doran, Graeme Pedamallu, Chandra Sekhar Ojesina, Akinyemi I. Wong, Raymond R. Y. Wang, Vivian W. Freeman, Samuel S. Lau, Tat San Kwong, Joseph Chan, Loucia K. Y. Fromer, Menachem May, Taymaa Worley, Michael J., Jr. Esselen, Katharine M. Elias, Kevin M. Lawrence, Michael Getz, Gad Smith, David I. Crum, Christopher P. Meyerson, Matthew Berkowitz, Ross S. Wong, Yick Fu TI Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cervical adenocarcinoma; genomic alternations; HPV ID ONCOGENIC MUTATIONS; HUMAN CANCERS; GENES; ACTIVATION; REVEALS; PIK3CA; CELLS; HPV16; ASSAY AB Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information. C1 [Chung, Tony K. H.; Cheung, Tak Hong; Yim, So Fan; Lau, Tat San; Kwong, Joseph; Chan, Loucia K. Y.; Wong, Yick Fu] Chinese Univ Hong Kong, Dept Obstet & Gynaecol, Hong Kong, Hong Kong, Peoples R China. [Van Hummelen, Paul; Ducar, Matthew D.; Thorner, Aaron R.; MacConaill, Laura E.; Meyerson, Matthew] Harvard Univ, Dana Farber Canc Inst, Sch Med, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Chan, Paul K. S.] Chinese Univ Hong Kong, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China. [Yu, Mei Y.] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong, Peoples R China. [Doran, Graeme] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Pedamallu, Chandra Sekhar; Ojesina, Akinyemi I.; Freeman, Samuel S.; Meyerson, Matthew] Broad Inst MIT & Harvard Univ, Canc Program, Cambridge, MA USA. [Pedamallu, Chandra Sekhar; Ojesina, Akinyemi I.; Meyerson, Matthew] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. [Wong, Raymond R. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Labs, Boston, MA 02115 USA. [Wang, Vivian W.; Smith, David I.] Mayo Clin, Dept Pathol & Lab Med, Rochester, MN USA. [Fromer, Menachem] Mt Sinai Sch Med, Div Psychiat Genom, New York, NY USA. [May, Taymaa] Princess Margaret Canc Ctr, Div Gynecol Oncol, Toronto, ON, Canada. [Worley, Michael J., Jr.; Esselen, Katharine M.; Elias, Kevin M.; Berkowitz, Ross S.; Wong, Yick Fu] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Lawrence, Michael; Getz, Gad] Broad Inst Harvard & MIT, Canc Genom Informat & Computat Biol, Cambridge, MA USA. [Crum, Christopher P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wong, YF (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA. EM Ross_berkowitz@dfci.harvard.edu; yfwong@rics.bwh.harvard.edu RI Chan, Paul/J-9360-2013; OI Ojesina, Akinyemi/0000-0003-0755-3639; Elias, Kevin/0000-0003-1502-5553 FU Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong FX Grant sponsor: The Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong NR 34 TC 6 Z9 6 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD AUG 15 PY 2015 VL 137 IS 4 BP 776 EP 783 DI 10.1002/ijc.29456 PG 8 WC Oncology SC Oncology GA CK7QY UT WOS:000356428400003 PM 25626421 ER PT J AU Platz, EA Drake, CG Wilson, KM Sutcliffe, S Kenfield, SA Mucci, LA Stampfer, MJ Willett, WC Camargo, CA Giovannucci, E AF Platz, Elizabeth A. Drake, Charles G. Wilson, Kathryn M. Sutcliffe, Siobhan Kenfield, Stacey A. Mucci, Lorelei A. Stampfer, Meir J. Willett, Walter C. Camargo, Carlos A., Jr. Giovannucci, Edward TI Asthma and risk of lethal prostate cancer in the Health Professionals Follow-Up Study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE asthma; hayfever; prostate cancer; risk; men ID REGULATORY T-CELLS; ALLERGIC RHINITIS; HAY-FEVER; US MEN; DISEASE; INFLAMMATION; POPULATION; MONTREAL; HISTORY; COHORT AB Inflammation, and more generally, the immune response are thought to influence the development of prostate cancer. To determine the components of the immune response that are potentially contributory, we prospectively evaluated the association of immune-mediated conditions, asthma and hayfever, with lethal prostate cancer risk in the Health Professionals Follow-up Study. We included 47,880 men aged 40-75 years with no prior cancer diagnosis. On the baseline questionnaire in 1986, the men reported diagnoses of asthma and hayfever and year of onset. On the follow-up questionnaires, they reported new asthma and prostate cancer diagnoses. We used Cox proportional hazards regression to estimate relative risks (RRs). In total, 9.2% reported ever having been diagnosed with asthma. In all, 25.3% reported a hayfever diagnosis at baseline. During 995,176 person-years of follow-up by 2012, we confirmed 798 lethal prostate cancer cases (diagnosed with distant metastases, progressed to distant metastasis or died of prostate cancer [N = 625]). Ever having a diagnosis of asthma was inversely associated with risk of lethal (RR = 0.71, 95% confidence interval [CI] = 0.51-1.00) and fatal (RR = 0.64, 95% CI = 0.42-0.96) disease. Hayfever with onset in the distant past was possibly weakly positively associated with risk of lethal (RR = 1.10, 95% CI = 0.92-1.33) and fatal (RR = 1.12, 95% CI = 0.91-1.37) disease. Men who were ever diagnosed with asthma were less likely to develop lethal and fatal prostate cancer. Our findings may lead to testable hypotheses about specific immune profiles in the etiology of lethal prostate cancer. C1 [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Platz, Elizabeth A.; Drake, Charles G.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Platz, Elizabeth A.; Drake, Charles G.] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. [Platz, Elizabeth A.; Drake, Charles G.] Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA. [Drake, Charles G.] Johns Hopkins Univ, Sch Med, Dept Immunol, Baltimore, MD USA. [Wilson, Kathryn M.; Mucci, Lorelei A.; Stampfer, Meir J.; Willett, Walter C.; Camargo, Carlos A., Jr.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wilson, Kathryn M.; Mucci, Lorelei A.; Stampfer, Meir J.; Willett, Walter C.; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Sutcliffe, Siobhan] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA. [Sutcliffe, Siobhan] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Kenfield, Stacey A.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. [Stampfer, Meir J.; Willett, Walter C.; Camargo, Carlos A., Jr.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Room E6132,615 N Wolfe St, Baltimore, MD 21205 USA. EM eplatz1@jhu.edu OI Sutcliffe, Siobhan/0000-0002-4613-8107 FU National Cancer Institute [P01 CA55075, R01 CA133891, P30 CA006973, P50 CA58236]; National Heart, Lung and Blood Institute [R01 HL35464] FX Grant sponsor: The National Cancer Institute; Grant numbers: P01 CA55075, R01 CA133891 (Harvard), P30 CA006973, P50 CA58236 (Johns Hopkins); Grant sponsor: The National Heart, Lung and Blood Institute; Grant number: R01 HL35464 (Harvard) NR 49 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD AUG 15 PY 2015 VL 137 IS 4 BP 949 EP 958 DI 10.1002/ijc.29463 PG 10 WC Oncology SC Oncology GA CK7QY UT WOS:000356428400021 PM 25648070 ER PT J AU de Almeida, FR Alencar, MCN de Souza, AC Esteves, WAD Cunha, TDM Barbosa, MM Tan, TC Nunes, MCP AF de Almeida, Fernanda Rodrigues Alencar, Maria Clara N. de Souza, Aline Cristina de Magalhaes Esteves, Willian Antonio Meinberg Cunha, Tassia de Oliveira Barbosa, Marcia Melo Tan, Timothy C. Pereira Nunes, Maria Carmo TI Ventilatory inefficiency in patients with rheumatic mitral stenosis SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Mitral stenosis; Ventilatory efficiency; VE/VCO2 slope; Functional capacity ID BALLOON VALVULOPLASTY; EXERCISE VENTILATION; HEART-FAILURE; ASSOCIATION; CAPACITY C1 [de Almeida, Fernanda Rodrigues; Alencar, Maria Clara N.; de Souza, Aline Cristina; de Magalhaes Esteves, Willian Antonio; Meinberg Cunha, Tassia de Oliveira; Pereira Nunes, Maria Carmo] Univ Fed Minas Gerais, Sch Med, Postgrad Program Infect Dis & Trop Med, Belo Horizonte, MG, Brazil. [Barbosa, Marcia Melo] Hosp Socor, Ecoctr, Belo Horizonte, MG, Brazil. [Tan, Timothy C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. RP Nunes, MCP (reprint author), Univ Fed Minas Gerais, Dept Clin Med, Av Prof Alfredo Balena,190 Santa Efigenia, BR-30130100 Belo Horizonte, MG, Brazil. EM mcarmo@waymail.com.br NR 10 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 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD AUG 15 PY 2015 VL 193 BP 36 EP 38 DI 10.1016/j.ijcard.2015.05.036 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK2PS UT WOS:000356053800007 PM 26005171 ER PT J AU Lo, WK Burakoff, R Goldberg, HJ Feldman, N Chan, WW AF Lo, Wai-Kit Burakoff, Robert Goldberg, Hilary J. Feldman, Natan Chan, Walter W. TI Pre-lung transplant measures of reflux on impedance are superior to pH testing alone in predicting early allograft injury SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Gastroesophageal reflux; Lung transplant; Multichannel intraluminal impedance; pH-monitoring; Allograft injury ID MULTICHANNEL INTRALUMINAL IMPEDANCE; BRONCHIOLITIS OBLITERANS SYNDROME; GASTROESOPHAGEAL-REFLUX; ESOPHAGEAL IMPEDANCE; REJECTION; RECIPIENTS; THERAPY; ACID; ASPIRATION; DISEASE AB AIM: To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding bolus reflux on multi-channel intraluminal impedance (MII) to predict early allograft injury. METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined MII-pH-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-pH testing and early allograft injury. Area under the receiver operating characteristic (ROC) curve (c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six pH-testing parameters and their corresponding MII measures were specified a priori. The pH parameters were upright, recumbent, and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright, recumbent, and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time. RESULTS: Thirty-two subjects (47% men, mean age: 55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary function, number of lungs transplanted (unilateral vs bilateral), and post-transplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve, or c-statistic, of each acid reflux parameter on pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition, the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux: overall reflux exposure (HR = 1.18, 95% CI: 1.01-1.36, P = 0.03), recumbent reflux exposure (HR = 1.25, 95% CI: 1.04-1.50, P = 0.01) and bolus clearance (HR = 1.09, 95% CI: 1.01-1.17, P = 0.02), but not with any pH-testing parameter measuring acid reflux alone. CONCLUSION: Pre-transplant MII measures of bolus reflux perform better than their pH-testing counterparts in predicting early allograft injury post-lung transplantation. C1 [Lo, Wai-Kit; Burakoff, Robert; Feldman, Natan; Chan, Walter W.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Lo, Wai-Kit] VA Boston Healthcare Syst, Dept Gastroenterol, Boston, MA 02130 USA. [Lo, Wai-Kit; Burakoff, Robert; Goldberg, Hilary J.; Chan, Walter W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Goldberg, Hilary J.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. RP Chan, WW (reprint author), Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA. EM wwchan@partners.org NR 31 TC 0 Z9 0 U1 0 U2 0 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD AUG 14 PY 2015 VL 21 IS 30 BP 9111 EP 9117 DI 10.3748/wjg.v21.i30.9111 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS6ZS UT WOS:000362233700011 PM 26290637 ER PT J AU Huang, JL Marco, E Pinello, L Yuan, GC AF Huang, Jialiang Marco, Eugenio Pinello, Luca Yuan, Guo-Cheng TI Predicting chromatin organization using histone marks SO GENOME BIOLOGY LA English DT Article ID HI-C DATA; HUMAN GENOME; ARCHITECTURE; FEATURES; DOMAINS; INTERACTOME; ANNOTATION; EXPRESSION; PRINCIPLES; CELLS AB Genome-wide mapping of three dimensional chromatin organization is an important yet technically challenging task. To aid experimental effort and to understand the determinants of long-range chromatin interactions, we have developed a computational model integrating Hi-C and histone mark ChIP-seq data to predict two important features of chromatin organization: chromatin interaction hubs and topologically associated domain (TAD) boundaries. Our model accurately and robustly predicts these features across datasets and cell types. Cell-type specific histone mark information is required for prediction of chromatin interaction hubs but not for TAD boundaries. Our predictions provide a useful guide for the exploration of chromatin organization. C1 [Huang, Jialiang; Marco, Eugenio; Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Huang, Jialiang; Marco, Eugenio; Pinello, Luca; Yuan, Guo-Cheng] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Yuan, Guo-Cheng] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Yuan, GC (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM gcyuan@jimmy.harvard.edu FU NIH [5R21HG006778]; NHGRI Career Development Award [K99HG008399] FX We thank Dr. Jian Xu for the comments on the manuscript. This work was supported by the NIH grant 5R21HG006778 to G.C.Y. L.P. is supported by NHGRI Career Development Award K99HG008399. NR 40 TC 9 Z9 11 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PD AUG 14 PY 2015 VL 16 AR 162 DI 10.1186/s13059-015-0740-z PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CQ5YW UT WOS:000360682600002 PM 26272203 ER PT J AU Barbie, DA Kennedy, BK AF Barbie, David A. Kennedy, Brian K. TI Doxycycline: new tricks for an old drug SO ONCOTARGET LA English DT Editorial Material ID TETRACYCLINES; INHIBITION; CELLS C1 [Barbie, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Barbie, DA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM DBARBIE@PART-NERS.ORG NR 8 TC 3 Z9 3 U1 0 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 14 PY 2015 VL 6 IS 23 BP 19336 EP 19337 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CP8HY UT WOS:000360135300001 PM 26305845 ER PT J AU Kannan, S Kurupati, RK Doyle, SA Freeman, GJ Schmader, KE Ertl, HCJ AF Kannan, Senthil Kurupati, Raj K. Doyle, Susan A. Freeman, Gordon J. Schmader, Kenneth E. Ertl, Hildegund C. J. TI BTLA expression declines on B cells of the aged and is associated with low responsiveness to the trivalent influenza vaccine SO ONCOTARGET LA English DT Article DE BTLA; aging; HSV; immunosenescence; influenza ID T-CELLS; RESPONSES; MAINTENANCE; REPERTOIRE; LYMPHOCYTE; SENESCENCE; PATHWAY; MICE AB Virus-neutralizing antibody and B cell responses to influenza A viruses were measured in 35 aged and 28 middle-aged individuals following vaccination with the 2012 and 2013 trivalent inactivated influenza vaccines. Antibody responses to the vaccine strains were lower in the aged. An analysis of B cell subsets by flow cytometry with stains for immunoregulators showed that B cells of multiple subsets from the aged as compared to younger human subjects showed differences in the expression of the co-inhibitor B and T lymphocyte attenuator (BTLA). Expression of BTLA inversely correlated with age and appears to be linked to shiftsing the nature of the response from IgM to IgG. High BTLA expression on mature B cells was linked to higher IgG responses to the H1N1 virus. Finally, high BTLA expression on isotype switched memory B cells was linked to better preservation of virus neutralizing antibody titers and improved recall responses to vaccination given the following year. C1 [Kannan, Senthil] Univ Penn, Biomed Grad Grp, Philadelphia, PA 19104 USA. [Kannan, Senthil; Kurupati, Raj K.; Ertl, Hildegund C. J.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Doyle, Susan A.; Schmader, Kenneth E.] Duke Univ, Med Ctr, Durham VA Med Ctr, GRECC, Durham, NC USA. [Doyle, Susan A.; Schmader, Kenneth E.] Duke Univ, Med Ctr, Ctr Study Aging & Human, Dev, Durham, NC USA. [Doyle, Susan A.; Schmader, Kenneth E.] Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ertl, HCJ (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. EM ertl@wistar.upenn.edu FU NIAID [BAA N01-AI-100018C]; Duke Pepper Older Americans Independence Center NIA [P30 AG028716] FX This work was funded by BAA N01-AI-100018C from NIAID and Duke Pepper Older Americans Independence Center NIA P30 AG028716. Our special thanks to all of the human subjects, who volunteered to donate their blood. NR 33 TC 1 Z9 1 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 14 PY 2015 VL 6 IS 23 BP 19445 EP 19455 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CP8HY UT WOS:000360135300022 PM 26277622 ER PT J AU Kovari, E Charidimou, A Herrmann, FR Giannakopoulos, P Bouras, C Gold, G AF Koevari, Enikoe Charidimou, Andreas Herrmann, Franois R. Giannakopoulos, Panteleimon Bouras, Constantin Gold, Gabriel TI No neuropathological evidence for a direct topographical relation between microbleeds and cerebral amyloid angiopathy SO ACTA NEUROPATHOLOGICA COMMUNICATIONS LA English DT Article ID SUPERFICIAL SIDEROSIS; CLINICAL-DIAGNOSIS; BRAIN MICROBLEEDS; ROTTERDAM-SCAN; MR-IMAGES; HEMORRHAGE; PREVALENCE; DISEASE AB Introduction: Cerebral microbleeds correspond to blood breakdown products, including hemosiderin-containing macrophages around small vessels on histological examination. Superficial lobar cerebral microbleeds are increasingly recognized on MRI as a biomarker of cerebral amyloid angiopathy but the direct association between amyloid-laden vessels burden and cerebral microbleeds has yet to be validated neuropathologically. To address this issue, we examined the frequency of histopathologically-defined cerebral microbleeds in different brain regions and their relationship with cerebral amyloid angiopathy in a large autopsy population. Results: The frontal, parietal and occipital cortex as well as the adjacent white matter and basal ganglia of 113 consecutive autopsies were examined. Cerebral microbleedss were identified on haematoxylin-eosin-stained histological slides, cerebral amyloid angiopathy using anti-amyloid antibody. Cerebral microbleeds were present in 92.9 % of the cases and cerebral amyloid angiopathy in 44.3 % of them. Cerebral microbleeds were more frequent in parietal and frontal lobes followed by the occipital region and basal ganglia. In contrast, cerebral amyloid angiopathy was most frequent in the occipital lobe. There was no significant topographical association between cerebral amyloid angiopathy presence or severity and cerebral microbleeds in any brain region. In lobar areas, cerebral amyloid angiopathy was found in the cortex, predominantly affecting pial arteries and their superficial cortical branches, in contrast to microbleeds which were mainly in the white matter and occurred around deeper arteries and arterioles, including the subcortical segment of long penetrating branches of pial vessels. Conclusions: Our study does not support a direct relation between cerebral microbleeds and cerebral amyloid angiopathy burden at the neuropathological level, raising intriguing questions on the potential pathophysiological mechanisms of cerebral microbleeds in the context of cerebral amyloid angiopathy or other small vessel disease pathology. C1 [Koevari, Enikoe; Giannakopoulos, Panteleimon; Bouras, Constantin] Univ Hosp Geneva, Dept Mental Hlth & Psychiat, CH-1225 Geneva, Switzerland. [Koevari, Enikoe; Giannakopoulos, Panteleimon; Bouras, Constantin] Univ Geneva, CH-1225 Geneva, Switzerland. [Charidimou, Andreas] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA 02114 USA. [Herrmann, Franois R.; Bouras, Constantin; Gold, Gabriel] Univ Hosp Geneva, Dept Internal Med Rehabil & Geriatr, CH-1226 Thonex, Switzerland. [Herrmann, Franois R.; Bouras, Constantin; Gold, Gabriel] Univ Geneva, CH-1226 Thonex, Switzerland. RP Kovari, E (reprint author), Univ Hosp Geneva, Dept Mental Hlth & Psychiat, 2 Chemin Petit Bel Air, CH-1225 Geneva, Switzerland. EM eniko.kovari@hcuge.ch RI HERRMANN, Francois/B-6710-2011 OI HERRMANN, Francois/0000-0003-1312-1517 NR 40 TC 6 Z9 6 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2051-5960 J9 ACTA NEUROPATHOL COM JI Acta Neuropathol. Commun. PD AUG 14 PY 2015 VL 3 AR 49 DI 10.1186/s40478-015-0228-9 PG 7 WC Neurosciences SC Neurosciences & Neurology GA CP9WZ UT WOS:000360247400001 PM 26268348 ER PT J AU Hackett, TA Guo, Y Clause, A Hackett, NJ Garbett, K Zhang, P Polley, DB Mirnics, K AF Hackett, Troy A. Guo, Yan Clause, Amanda Hackett, Nicholas J. Garbett, Krassimira Zhang, Pan Polley, Daniel B. Mirnics, Karoly TI Transcriptional maturation of the mouse auditory forebrain SO BMC GENOMICS LA English DT Article DE Synapse; Plasticity; Development; Critical period; Cortex; Thalamus; Neurotransmission; Neuromodulation; Extracellular matrix; Myelination; RNAseq; Pathway analysis; Sequencing; RNA ID DIFFERENTIAL EXPRESSION ANALYSIS; CHONDROITIN SULFATE PROTEOGLYCAN; LATERAL GENICULATE-NUCLEUS; SUPERIOR OLIVARY COMPLEX; SEQUENCE COUNT DATA; RNA-SEQ DATA; GENE-EXPRESSION; INFERIOR COLLICULUS; VISUAL-CORTEX; CRITICAL PERIOD AB Background: The maturation of the brain involves the coordinated expression of thousands of genes, proteins and regulatory elements over time. In sensory pathways, gene expression profiles are modified by age and sensory experience in a manner that differs between brain regions and cell types. In the auditory system of altricial animals, neuronal activity increases markedly after the opening of the ear canals, initiating events that culminate in the maturation of auditory circuitry in the brain. This window provides a unique opportunity to study how gene expression patterns are modified by the onset of sensory experience through maturity. As a tool for capturing these features, next-generation sequencing of total RNA (RNAseq) has tremendous utility, because the entire transcriptome can be screened to index expression of any gene. To date, whole transcriptome profiles have not been generated for any central auditory structure in any species at any age. In the present study, RNAseq was used to profile two regions of the mouse auditory forebrain (A1, primary auditory cortex; MG, medial geniculate) at key stages of postnatal development (P7, P14, P21, adult) before and after the onset of hearing (similar to P12). Hierarchical clustering, differential expression, and functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all genes. Selected genesets related to neurotransmission, developmental plasticity, critical periods and brain structure were highlighted. An accessible repository of the entire dataset was also constructed that permits extraction and screening of all data from the global through single-gene levels. To our knowledge, this is the first whole transcriptome sequencing study of the forebrain of any mammalian sensory system. Although the data are most relevant for the auditory system, they are generally applicable to forebrain structures in the visual and somatosensory systems, as well. Results: The main findings were: (1) Global gene expression patterns were tightly clustered by postnatal age and brain region; (2) comparing A1 and MG, the total numbers of differentially expressed genes were comparable from P7 to P21, then dropped to nearly half by adulthood; (3) comparing successive age groups, the greatest numbers of differentially expressed genes were found between P7 and P14 in both regions, followed by a steady decline in numbers with age; (4) maturational trajectories in expression levels varied at the single gene level (increasing, decreasing, static, other); (5) between regions, the profiles of single genes were often asymmetric; (6) GSEA revealed that genesets related to neural activity and plasticity were typically upregulated from P7 to adult, while those related to structure tended to be downregulated; (7) GSEA and pathways analysis of selected functional networks were not predictive of expression patterns in the auditory forebrain for all genes, reflecting regional specificity at the single gene level. Conclusions: Gene expression in the auditory forebrain during postnatal development is in constant flux and becomes increasingly stable with age. Maturational changes are evident at the global through single gene levels. Transcriptome profiles in A1 and MG are distinct at all ages, and differ from other brain regions. The database generated by this study provides a rich foundation for the identification of novel developmental biomarkers, functional gene pathways, and targeted studies of postnatal maturation in the auditory forebrain. C1 [Hackett, Troy A.] Vanderbilt Univ, Sch Med, Dept Hearing & Speech Sci, Nashville, TN 37212 USA. [Clause, Amanda; Polley, Daniel B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Eaton Peabody Labs,Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Hackett, Nicholas J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Guo, Yan; Zhang, Pan] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37235 USA. [Garbett, Krassimira; Mirnics, Karoly] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37235 USA. [Mirnics, Karoly] Vanderbilt Univ, Vanderbilt Inst Integrat Biosyst Res & Educ, Nashville, TN 37235 USA. [Mirnics, Karoly] Univ Szeged, Dept Psychiat, H-6725 Szeged, Hungary. [Hackett, Troy A.; Mirnics, Karoly] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA. RP Hackett, TA (reprint author), Vanderbilt Univ, Sch Med, Dept Hearing & Speech Sci, Nashville, TN 37212 USA. EM troy.a.hackett@vanderbilt.edu FU NIH/NIDCD [K18 DC012527, R01 DC009836]; Vanderbilt Kennedy Center infrastructure [P30-HD015052-33] FX The authors gratefully acknowledge the support of NIH/NIDCD grants K18 DC012527 to T.A.H. and R01 DC009836 to D.P. Special thanks to Tia Hughes and Cara Sutcliffe in the VANTAGE core at Vanderbilt University for expert assistance with RNA isolation and sample quality assessment; Dr. Holli Hutcheson-Dilks in the VANTAGE core for design and supervision of RNA sequencing; the Vanderbilt Kennedy Center infrastructure grant P30-HD015052-33. NR 123 TC 1 Z9 1 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD AUG 14 PY 2015 VL 16 AR 606 DI 10.1186/s12864-015-1709-8 PG 29 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CO9VW UT WOS:000359525300002 PM 26271746 ER PT J AU Vargas-Santos, AB Castelar-Pinheiro, GD Coutinho, ESF Schumacher, HR Singh, JA Schlesinger, N AF Vargas-Santos, Ana Beatriz Castelar-Pinheiro, Geraldo da Rocha Freire Coutinho, Evandro Silva Schumacher, H. Ralph, Jr. Singh, Jasvinder A. Schlesinger, Naomi TI Adherence to the 2012 American College of Rheumatology (ACR) Guidelines for Management of Gout: A Survey of Brazilian Rheumatologists SO PLOS ONE LA English DT Article ID CURRENT PRESCRIBING PRACTICES; EVIDENCE-BASED RECOMMENDATIONS; URATE-LOWERING DRUGS; PHYSICIAN QUESTIONNAIRE; TASK-FORCE; ARTHRITIS; DIAGNOSIS; CARE; HYPERURICEMIA; COLCHICINE AB Objective To describe the current pharmacological approach to gout treatment reported by rheumatologists in Brazil. Methods We performed a cross-sectional survey study using an online questionnaire e-mailed to 395 rheumatologists, randomly selected, from among the members of the Brazilian Society of Rheumatology. Results Three hundred and nine rheumatologists (78.2%) responded to the survey. For acute gout attacks, combination therapy (NSAIDs or steroid + colchicine) was often used, even in monoarticular involvement, and colchicine was commonly started as monotherapy after 36 hours or more from onset of attack. During an acute attack, urate-lowering therapy (ULT) was withdrawn by approximately a third of rheumatologists. Anti-inflammatory prophylaxis (98% colchicine) was initiated when ULT was started in most cases (92.4%), but its duration was varied. Most (70%) respondents considered the target serum uric acid level to be less than 6 mg/dl. Approximately 50% of rheumatologists reported starting allopurinol at doses of 100 mg daily or less and 42% reported the initial dose to be 300 mg daily in patients with normal renal function. ULT was maintained indefinitely in 76% of gout patients with tophi whereas in gout patients without tophi its use was kept indefinitely in 39.6%. Conclusion This is the first study evaluating gout treatment in a representative, random sample of Brazilian rheumatologists describing common treatment practices among these specialists. We identified several gaps in reported gout management, mainly concerning the use of colchicine and ULT and the duration of anti-inflammatory prophylaxis and ULT. Since rheumatologists are considered as opinion leaders in this disease, a program for improving quality of care for gout patients should focus on increasing their knowledge in this common disease. C1 [Vargas-Santos, Ana Beatriz; Castelar-Pinheiro, Geraldo da Rocha] Univ Estado Rio de Janeiro, Dept Internal Med, Div Rheumatol, BR-20550011 Rio De Janeiro, RJ, Brazil. [Freire Coutinho, Evandro Silva] Fundacao Oswaldo Cruz, Escola Nacl Saude Publ Sergio Arouca, Dept Epidemiol, Rio De Janeiro, RJ, Brazil. [Schumacher, H. Ralph, Jr.] Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Schlesinger, Naomi] Rutgers State Univ, Robert Wood Johnson Med Sch, Div Rheumatol, Dept Med, New Brunswick, NJ 08903 USA. RP Vargas-Santos, AB (reprint author), Univ Estado Rio de Janeiro, Dept Internal Med, Div Rheumatol, BR-20550011 Rio De Janeiro, RJ, Brazil. EM anabvargas@gmail.com OI Vargas dos Santos, Ana Beatriz/0000-0001-5307-0254; Pinheiro, Geraldo/0000-0002-7778-569X FU Astrazeneca; Abbvie; Takeda; Ardea; Merck; Metabolex; Novartis Pharmaceutical Corporation; Regeneron; Savient; Allergan; Sobi; BMS; Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Institute of Aging (NIA); National Cancer Institute (NCI) FX Ana Beatriz Vargas-Santos has received consultant fee from Astrazeneca; H. Ralph Schumacher Jr. has received research grants from Abbvie and Takeda, and consultant fees from Abbvie, Ardea, AstraZeneca, Merck, Metabolex, Novartis Pharmaceutical Corporation, Regeneron and Takeda; Jasvinder A. Singh has received research and travel grants from Takeda and Savient, and consultant fees from Savient, Takeda, Allergan and Regeneron; Naomi Schlesinger has received grants from Novartis Pharmaceutical Corporation, consultant fees from Novartis Pharmaceutical Corporation, Sobi, BMS, is on the Speakers' Bureau of Novartis Pharmaceutical Corporation and Takeda, and serves on the advisory boards of Novartis Pharmaceutical Corporation, Takeda and Sobi. Jasvinder A. Singh is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institute of Aging (NIA) and National Cancer Institute (NCI). Geraldo da Rocha Castelar-Pinheiro and Evandro Silva Freire Coutinho have declared that no competing interests exist. This does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials. NR 51 TC 1 Z9 1 U1 4 U2 5 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 AUG 14 PY 2015 VL 10 IS 8 AR e0135805 DI 10.1371/journal.pone.0135805 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO9KD UT WOS:000359493600115 PM 26274585 ER PT J AU Liu, XH Bauma, WA Cardozo, C AF Liu, Xin-Hua Bauma, William A. Cardozo, Christopher TI ANKRD1 modulates inflammatory responses in C2C12 myoblasts through feedback inhibition of NF-kappa B signaling activity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Inflammation; NF-kB signaling; AnkrD1; Myoblasts ID ANKYRIN-REPEAT PROTEIN; SPINAL MUSCULAR-ATROPHY; SKELETAL-MUSCLE; CONGENITAL MYOPATHY; I-BAND; EXPRESSION; ACTIVATION; CARP; IDENTIFICATION; TRANSCRIPTION AB Transcription factors of the nuclear factor-kappa B (NF-kappa B) family play a pivotal role in inflammation, immunity and cell survival responses. Recent studies revealed that NF-kappa B also regulates the processes of muscle atrophy. NF-kappa B activity is regulated by various factors, including ankyrin repeat domain 2 (AnkrD2), which belongs to the muscle ankyrin repeat protein family. Another member of this family, AnkrD1 is also a transcriptional effector. The expression levels of AnkrD1 are highly upregulated in denervated skeletal muscle, suggesting an involvement of AnkrD1 in NF-kappa B mediated cellular responses to paralysis. However, the molecular mechanism underlying the interactive role of AnkrD1 in NF-kappa B mediated cellular responses is not well understood. In the current study, we examined the effect of AnkrD1 on NF-kappa B activity and determined the interactions between AnkrD1 expression and NF-kappa B signaling induced by TNF alpha in differentiating C2C12 myoblasts. TNF alpha upregulated AnkrD1 mRNA and protein levels. AnkrD1-siRNA significantly increased TNF alpha-induced transcriptional activation of NF-kappa B, whereas overexpression of AnkrD1 inhibited TNF alpha-induced NF-kappa B activity. Co-immunoprecipitation studies demonstrated that AnkrD1 was able to bind p50 subunit of NF-kappa B and vice versa. Finally, CHIP assays revealed that AnkrD1 bound chromatin at a NF-kappa B binding site in the AnrkD2 promoter and required NF-kappa B to do so. These results provide evidence of signaling integration between AnkrD1 and NF-kappa B pathways, and suggest a novel anti-inflammatory role of AnkrD1 through feedback inhibition of NF-kappa B transcriptional activity by which AnkrD1 modulates the balance between physiological and pathological inflammatory responses in skeletal muscle. Published by Elsevier Inc. C1 [Liu, Xin-Hua; Bauma, William A.; Cardozo, Christopher] James J Peter VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY 10468 USA. [Liu, Xin-Hua; Bauma, William A.; Cardozo, Christopher] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Bauma, William A.; Cardozo, Christopher] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Cardozo, Christopher] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. RP Cardozo, C (reprint author), James J Peter VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM chris.cardozo@va.gov FU Veterans Health Administration, Rehabilitation Research and Development Service [B9212C, F7756R] FX This work was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (Grants B9212C, F7756R). NR 34 TC 2 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 14 PY 2015 VL 464 IS 1 BP 208 EP 213 DI 10.1016/j.bbrc.2015.06.118 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CO5AY UT WOS:000359173200033 PM 26102030 ER PT J AU Frelinger, AL Grace, RF Gerrits, AJ Berny-Lang, MA Brown, T Carmichael, SL Neufeld, EJ Michelson, AD AF Frelinger, Andrew L., III Grace, Rachael F. Gerrits, Anja J. Berny-Lang, Michelle A. Brown, Travis Carmichael, Sabrina L. Neufeld, Ellis J. Michelson, Alan D. TI Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP SO BLOOD LA English DT Article ID PRIMARY IMMUNE THROMBOCYTOPENIA; FLOW-CYTOMETRIC EVALUATION; IB-IX COMPLEX; AUTOIMMUNE THROMBOCYTOPENIA; ADENOSINE-DIPHOSPHATE; RETICULATED PLATELETS; ACTIVATION; CHILDREN; HEMORRHAGE; PURPURA AB Immune thrombocytopenia (ITP) patients with similarly low platelet counts differ in their tendency to bleed. To determine if differences in platelet function in ITP patients account for this variation in bleeding tendency, we conducted a single-center, cross-sectional study of pediatric patients with ITP. Bleeding severity (assessed by standardized bleeding score) and platelet function (assessed by whole blood flow cytometry) with and without agonist stimulation was evaluated in 57 ITP patients (median age, 9.9 years). After adjustment for platelet count, higher levels of thrombin receptor activating peptide (TRAP)-stimulated percent P-selectin- and activated glycoprotein (GP) IIb-IIIa-positive platelets were significantly associated with a lower bleeding score, whereas higher levels of immature platelet fraction (IPF), TRAP-stimulated platelet surface CD42b, unstimulated platelet surface P-selectin, and platelet forward light scatter (FSC) were associated with a higher bleeding score. Thus, platelet function tests related to platelet age (IPF, FSC) and activation through the protease activated receptor 1 (PAR1) thrombin receptor (TRAP-stimulated P-selectin, activated GPIIb-IIIa, and CD42b), independent of platelet count, are associated with concurrent bleeding severity in ITP. These tests may be useful markers of future bleeding risk in ITP. C1 [Frelinger, Andrew L., III; Gerrits, Anja J.; Berny-Lang, Michelle A.; Carmichael, Sabrina L.; Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Platelet Res Studies,Boston Childrens Hosp, Boston, MA 02115 USA. [Frelinger, Andrew L., III; Grace, Rachael F.; Gerrits, Anja J.; Berny-Lang, Michelle A.; Brown, Travis; Carmichael, Sabrina L.; Neufeld, Ellis J.; Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. RP Frelinger, AL (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Ctr Platelet Res Studies, Karp 07212,300 Longwood Ave, Boston, MA 02115 USA. EM andrew.frelinger@childrens.harvard.edu OI Grace, Fergal/0000-0002-3144-5999 NR 29 TC 9 Z9 9 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD AUG 13 PY 2015 VL 126 IS 7 BP 873 EP 879 DI 10.1182/blood-2015-02-628461 PG 7 WC Hematology SC Hematology GA CQ3VC UT WOS:000360530800010 PM 26138687 ER PT J AU Gunasekera, D Ettinger, RA Fletcher, SN James, EA Liu, MC Barrett, JC Withycombe, J Matthews, DC Epstein, MS Hughes, RJ Pratt, KP AF Gunasekera, Devi Ettinger, Ruth A. Fletcher, Shelley Nakaya James, Eddie A. Liu, Maochang Barrett, John C. Withycombe, Janice Matthews, Dana C. Epstein, Melinda S. Hughes, Richard J. Pratt, Kathleen P. CA Personalized Approaches Therapies TI Factor VIII gene variants and inhibitor risk in African American hemophilia A patients SO BLOOD LA English DT Article ID T-CELL RESPONSES; HIGS COMBINED COHORT; IMMUNE-RESPONSES; EPITOPE IDENTIFICATION; F8; MUTATION; SUBSTITUTION; RECOGNITION; TOLERANCE; CHILDREN AB African American hemophilia A (HA) patients experience a higher incidence of neutralizing anti-factor VIII (FVIII) antibodies ("inhibitors") vis-a-vis white patients. Nonsynonymous single-nucleotide polymorphisms (ns-SNPs) in the F8 gene encoding FVIII-H484, FVIII-E1241, and FVIII-V2238 are more prevalent in African Americans. This study tested the hypothesis that immune responses to these sites provoke inhibitors. Blood samples were obtained from 174 African American and 198 white HA subjects and their F8 gene sequences determined. Major histocompatibility complex class II binding and T-cell recognition of polymorphic sequences were evaluated using quantitative binding assays and HLA-DRB1 tetramers. Peptides corresponding to 4 common ns-SNPs showed limited binding to 11 HLA-DRB1 proteins. CD4 T cells from 22 subjects treated with FVIII products having sequences at residues FVIII-484, 1241, and 2238 differing from those of putative proteins encoded by their F8 genes did not show high-avidity tetramer binding, whereas positive-control staining of tetanus-specific CD4 T cells was routinely successful. African Americans with an intron-22 inversion mutation showed a 2-3 times-higher inhibitor incidence than whites with the same mutation(odds ratio = 2.3 [1.1-5.0, P = .04]), but this did not correlate with any of the ns-SNPs. We conclude that immune responses to "sequence-mismatched" FVIII products are unlikely to contribute appreciably to the inhibitor incidence in African Americans. C1 [Gunasekera, Devi; Pratt, Kathleen P.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Gunasekera, Devi; Ettinger, Ruth A.; Liu, Maochang; Pratt, Kathleen P.] Puget Sound Blood Ctr Res Inst, Seattle, WA USA. [Fletcher, Shelley Nakaya] Puget Sound Blood Ctr, Genom Lab, Seattle, WA 98104 USA. [James, Eddie A.] Benaroya Res Inst, Seattle, WA USA. [Barrett, John C.] Virginia Commonwealth Univ, Cent Virginia Ctr Coagulat Disorders, Richmond, VA USA. [Withycombe, Janice] Palmetto Hlth, Columbia, SC USA. [Matthews, Dana C.] Seattle Childrens Hosp, Pediat Canc & Blood Disorders Ctr, Seattle, WA USA. [Epstein, Melinda S.; Hughes, Richard J.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. RP Pratt, KP (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med MED A3075, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM kathleen.pratt@usuhs.edu FU National Institutes of Health National Heart, Lung, and Blood Institute [1RC2-HL101851]; CSL Behring and Bayer FX This work was supported by National Institutes of Health National Heart, Lung, and Blood Institute grant 1RC2-HL101851, and unrestricted hemophilia research grants from CSL Behring and Bayer (K.P.P.). NR 47 TC 8 Z9 8 U1 2 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD AUG 13 PY 2015 VL 126 IS 7 BP 895 EP 904 DI 10.1182/blood-2014-09-599365 PG 10 WC Hematology SC Hematology GA CQ3VC UT WOS:000360530800013 PM 25617427 ER PT J AU Rajkumar, SV Richardson, P Miguel, JFS AF Rajkumar, S. Vincent Richardson, Paul Miguel, Jesus F. San TI Guidelines for determination of the number of prior lines of therapy in multiple myeloma SO BLOOD LA English DT Letter ID BORTEZOMIB C1 [Rajkumar, S. Vincent] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Richardson, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miguel, Jesus F. San] Univ Navarra Clin, Inst Invest Sanitaria Navarra, Ctr Invest Med Aplicada, Pamplona, Spain. RP Rajkumar, SV (reprint author), Mayo Clin, Div Hematol, Rochester, MN 55905 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 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 AUG 13 PY 2015 VL 126 IS 7 BP 921 EP 922 DI 10.1182/blood-2015-05-647636 PG 2 WC Hematology SC Hematology GA CQ3VC UT WOS:000360530800017 PM 26272048 ER PT J AU Livraghi, L Garber, JE AF Livraghi, Luca Garber, Judy E. TI PARP inhibitors in the management of breast cancer: current data and future prospects SO BMC MEDICINE LA English DT Review DE BRCA; Breast cancer; PARP inhibitors; Poly(ADP-ribose) polymerases ID POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; ADVANCED SOLID TUMORS; RECOMBINATION DEFICIENCY HRD; RECURRENT EPITHELIAL OVARIAN; RANDOMIZED PHASE-2 TRIAL; BRCA MUTATION CARRIERS; EPOTHILONE-B ANALOG; II CLINICAL-TRIAL; DNA-REPAIR DEFECT; HOMOLOGOUS RECOMBINATION AB Poly(ADP-ribose) polymerases (PARP) are enzymes involved in DNA-damage repair. Inhibition of PARPs is a promising strategy for targeting cancers with defective DNA-damage repair, including BRCA1 and BRCA2 mutation-associated breast and ovarian cancers. Several PARP inhibitors are currently in trials in the adjuvant, neoadjuvant, and metastatic settings for the treatment of ovarian, BRCA-mutated breast, and other cancers. We herein review the development of PARP inhibitors and the basis for the excitement surrounding these agents, their use as single agents and in combinations, as well as their toxicities, mechanisms of acquired resistance, and companion diagnostics. C1 [Livraghi, Luca; Garber, Judy E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM judy_garber@dfci.harvard.edu NR 127 TC 28 Z9 28 U1 4 U2 31 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD AUG 13 PY 2015 VL 13 AR 188 DI 10.1186/s12916-015-0425-1 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA CO8EA UT WOS:000359396800001 PM 26268938 ER PT J AU Stirman, SW Gutner, CA Crits-Christoph, P Edmunds, J Evans, AC Beidas, RS AF Stirman, Shannon Wiltsey Gutner, Cassidy A. Crits-Christoph, Paul Edmunds, Julie Evans, Arthur C. Beidas, Rinad S. TI Relationships between clinician-level attributes and fidelity-consistent and fidelity-inconsistent modifications to an evidence-based psychotherapy SO IMPLEMENTATION SCIENCE LA English DT Article ID COGNITIVE THERAPY; PSYCHOMETRIC PROPERTIES; RANDOMIZED-TRIAL; IMPLEMENTATION; FRAMEWORK; PROGRAMS; YOUTH; SUSTAINABILITY; DISSEMINATION; CONSULTATION AB Background: Clinicians often modify evidence-based psychotherapies (EBPs) when delivering them in routine care settings. There has been little study of factors associated with or implications of modifications to EBP protocols. This paper differentiates between fidelity-consistent and fidelity-inconsistent modifications and it examines the potential influence of two clinician characteristics, training outcomes, and attitudes toward EBPs on fidelity-consistent and fidelity-inconsistent modifications of cognitive behavioral therapy in a sample of clinicians who had been trained to deliver these treatments for children or adults. Methods: Survey and coded interview data collected 2 years after completion of training programs in cognitive behavioral therapy were used to examine associations between successful or unsuccessful completion of training, clinician attitudes, and modifications. Modifications endorsed by clinicians were categorized as fidelity-consistent or fidelity-inconsistent and entered as outcomes into separate regression models, with training success and attitudes entered as independent variables. Results: Successful completion of a training program was associated with subsequent fidelity-inconsistent modifications but not fidelity-consistent modifications. Therapists who reported greater openness to using EBPs prior to training reported more fidelity-consistent modifications at follow-up, and those who reported greater willingness to adopt EBPs if they found them appealing were more likely to make fidelity-inconsistent modifications. Conclusions: Implications of these findings for training, implementation, EBP sustainment, and future studies are discussed. Research on contextual and protocol-related factors that may impact decisions to modify EBPs will be an important future direction of study to complement to this research. C1 [Stirman, Shannon Wiltsey; Gutner, Cassidy A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Stirman, Shannon Wiltsey; Gutner, Cassidy A.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02130 USA. [Crits-Christoph, Paul] Univ Penn, Dept Psychiat, Perelman Sch Med, Ctr Psychotherapy Res, Philadelphia, PA 19104 USA. [Edmunds, Julie] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Evans, Arthur C.] Philadelphia Dept Behav Hlth & Dev DisAbil Serv, Philadelphia, PA USA. [Beidas, Rinad S.] Univ Penn, Dept Psychiat, Perelman Sch Med, Ctr Mental Hlth Policy & Serv Res, Philadelphia, PA 19104 USA. RP Stirman, SW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B3, Boston, MA 02130 USA. EM Shannon.Wiltsey-Stirman@VA.gov OI Wiltsey Stirman, Shannon/0000-0001-9917-5078 FU National Institute of Mental Health [MH010800, MH099179, MH083333]; VA [R25 MH080916] FX Funding for this research was provided by the National Institute of Mental Health (MH010800, MH099179, MH083333). At the time that the research was conducted, the first author and last authors were fellows at the NIMH and VA-funded Implementation Research Institute (R25 MH080916). Opinions expressed in this manuscript do not necessarily reflect the viewpoints of the Veterans Healthcare Administration or the National Institutes of Health. The authors wish to gratefully acknowledge the agencies, clinicians, and consumers who have participated in the research for their contributions to this project. A portion of the research findings were presented at the 6th Annual Conference on the Science of Dissemination and Implementation. NR 44 TC 4 Z9 4 U1 3 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD AUG 13 PY 2015 VL 10 AR 115 DI 10.1186/s13012-015-0308-z PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CO7KN UT WOS:000359338100001 ER PT J AU Zhang, YN Zhao, KT Fox, SG Kim, J Kirsch, DR Ferrante, RJ Morirnoto, RI Silverman, RB AF Zhang, Yinan Zhao, Kevin Tianmeng Fox, Susan G. Kim, Jinho Kirsch, Donald R. Ferrante, Robert J. Morimoto, Richard I. Silverman, Richard B. TI Tertiary Amine Pyrazolones and Their Salts as Inhibitors of Mutant Superoxide Dismutase 1-Dependent Protein Aggregation for the Treatment of Amyotrophic Lateral Sclerosis SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID POTENTIAL APPLICATION; BRAIN EXPOSURE; DESIGN; ALS; DERIVATIVES; TOXICITY; DRUGS; MOUSE AB Pyrazolone derivatives have previously been found to be inhibitors of Cu/Zn superoxide dismutase 1 (S OD 1) - dep en dent protein aggregation, which extended survival of an amyotrophic lateral sclerosis (ALS) mouse model. On the basis of ADME analysis, we describe herein a new series of tertiary amine-containing pyrazolones and their structure activity relationships. Further conversion to the conjugate salts greatly improved their solubility. Phosphate compound 17 exhibited numerous benefits both to cellular activity and to CNS-related drug-like properties in vitro and in vivo, including microsomal stability, tolerated toxicity, and blood brain barrier permeation. These results indicate that tertiary amine pyrazolones comprise a valuable class of ALS drug candidates. C1 [Zhang, Yinan; Zhao, Kevin Tianmeng; Silverman, Richard B.] Northwestern Univ, Dept Chem, Ctr Mol Innovat & Drug Discovery, Dept Mol Biosci,Chem Life Proc Inst, Evanston, IL 60208 USA. [Fox, Susan G.; Morimoto, Richard I.] Northwestern Univ, Rice Inst Biomed Res, Dept Mol Biosci, Evanston, IL 60208 USA. [Kim, Jinho; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA. [Kim, Jinho; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Kim, Jinho; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA. [Kim, Jinho; Ferrante, Robert J.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr 00 GR H, Pittsburgh, PA 15206 USA. [Kirsch, Donald R.] Cambria Pharmaceut, Cambridge, MA 02142 USA. RP Silverman, RB (reprint author), Northwestern Univ, Dept Chem, Ctr Mol Innovat & Drug Discovery, Dept Mol Biosci,Chem Life Proc Inst, 2145 Sheridan Rd, Evanston, IL 60208 USA. EM Agman@chem.northwestern.edu RI Zhang, Yinan/D-5769-2016 OI Zhang, Yinan/0000-0002-0362-1473 FU National Institutes of Health [1R43 NS057849]; ALS Association (TREAT program); Department of Defense [AL093052] FX We thank Prof. Meiyu Wang, College of Pharmacy, Soochew University, China, for her generous help with pharmacokinetic analysis and constructive discussions. We thank the National Institutes of Health (grant no. 1R43 NS057849), the ALS Association (TREAT program), and the Department of Defense (AL093052), for their generous support of this research. NR 32 TC 1 Z9 1 U1 3 U2 8 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 AUG 13 PY 2015 VL 58 IS 15 BP 5942 EP 5949 DI 10.1021/acs.jmedchem.5b00561 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CP2BY UT WOS:000359683700018 PM 26186011 ER PT J AU Chu, WH Zhou, D Gaba, V Liu, JL Li, SH Peng, X Xu, JB Dhavale, D Bagchi, DP d'Avignon, A Shakerdge, NB Bacskai, BJ Tu, ZD Kotzbauer, PT Mach, RH AF Chu, Wenhua Zhou, Dong Gaba, Vrinda Liu, Jialu Li, Shihong Peng, Xin Xu, Jinbin Dhavale, Dhruva Bagchi, Devika P. d'Avignon, Andre Shakerdge, Naomi B. Bacskai, Brian J. Tu, Zhude Kotzbauer, Paul T. Mach, Robert H. TI Design, Synthesis, and Characterization of 3-(Benzylidene)indolin-2-one Derivatives as Ligands for alpha-Synuclein Fibrils SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; IMAGING AGENT; IN-VITRO; A-BETA; PET; TAU; BRAIN; BINDING; PATHOLOGY AB A series of 3-(benzylidine)indolin-2-one derivatives were synthesized and evaluated for their in vitro binding to alpha synuclein (alpha-syn), beta amyloid (A beta), and tau fibrils. Compounds with a single double bond in the 3-position had only a modest affinity for alpha-syn and no selectivity for alpha-syn versus A beta or tau fibrils. Homologation to the corresponding diene analogues yielded a mixture of Z,E and E,E isomers; substitution of the indoline nitrogen with an N-benzyl group resulted in increased binding to alpha-syn and reasonable selectivity for alpha-syn versus and tau. Introduction of a para-nitro group into the benzene ring of the diene enabled separation of the Z,E and E,E isomers and led to the identification of the Z,E configuration as the more active regioisomer. The data described here provide key structural information in the design of probes which bind preferentially to alpha-syn versus A beta or tau fibrils. C1 [Chu, Wenhua; Zhou, Dong; Li, Shihong; Peng, Xin; Xu, Jinbin; Tu, Zhude; Mach, Robert H.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Gaba, Vrinda; Liu, Jialu; Dhavale, Dhruva; Bagchi, Devika P.; Kotzbauer, Paul T.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [d'Avignon, Andre] Washington Univ, Dept Chem, St Louis, MO 63130 USA. [Shakerdge, Naomi B.; Bacskai, Brian J.; Mach, Robert H.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Mach, RH (reprint author), Univ Penn, Radiol, Chem Bldg,231 South 34th St, Philadelphia, PA 19104 USA. EM rmach@mail.med.upenn.edu FU Michael J. Fox Alpha Synuclein Imaging Consortium, Washington University Institute of Clinical and Translational Sciences Grant [CTSA406]; Charles and Joanne Knight Alzheimer's Research Initiative of the Washington University Alzheimer's Disease Research Center; National Institutes of Health\ National Institute of General Medical Sciences Grant [8P41GM103422]; NIH Shared Instrument Grant program [S10 RR027207] FX This study was funded in part by the Michael J. Fox Alpha Synuclein Imaging Consortium, Washington University Institute of Clinical and Translational Sciences Grant CTSA406, and the Charles and Joanne Knight Alzheimer's Research Initiative of the Washington University Alzheimer's Disease Research Center. This study made use of the NIH/NIGMS Biomedical Mass Spectrometry Resource at Washington University in St. Louis, MO, which is supported by National Institutes of Health\ National Institute of General Medical Sciences Grant # 8P41GM103422. We would like to thank personnel of the Washington University Cyclotron Facility for [18F]fluoride production and the Department of Chemistry staff and the Washington University High Resolution NMR Facility for assistance with NMR spectra. Purchase of the 400 MHz NMR instrument was partially supported by S10 RR027207 from the NIH Shared Instrument Grant program. NR 31 TC 5 Z9 5 U1 1 U2 13 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 AUG 13 PY 2015 VL 58 IS 15 BP 6002 EP 6017 DI 10.1021/acs.jmedchem.5b00571 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CP2BY UT WOS:000359683700023 PM 26177091 ER PT J AU Asch, DA Rosin, R AF Asch, David A. Rosin, Roy TI Innovation as Discipline, Not Fad SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Asch, David A.; Rosin, Roy] Univ Penn, Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Asch, DA (reprint author), Univ Penn, Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. NR 4 TC 5 Z9 5 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 AUG 13 PY 2015 VL 373 IS 7 BP 592 EP 594 DI 10.1056/NEJMp1506311 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CP2LE UT WOS:000359707700003 PM 26267619 ER PT J AU Petersdorf, EW Malkki, M O'hUigin, C Carrington, M Gooley, T Haagenson, MD Horowitz, MM Spellman, SR Wang, T Stevenson, P AF Petersdorf, Effie W. Malkki, Mari O'hUigin, Colm Carrington, Mary Gooley, Ted Haagenson, Michael D. Horowitz, Mary M. Spellman, Stephen R. Wang, Tao Stevenson, Philip TI High HLA-DP Expression and Graft-versus-Host Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEMATOPOIETIC-CELL TRANSPLANTATION; UNRELATED-DONOR; MARROW TRANSPLANTATION; LYMPHOCYTE INFUSION; HLA-DPB1 MISMATCHES; HEPATITIS-B; ALLELES; ANTIGENS; INFECTION; RISK AB BACKGROUND Transplantation of hematopoietic cells from unrelated donors can cure blood disorders but carries a significant risk of acute graft-versus-host disease (GVHD). The risk is higher when the recipient and donor are HLA-DPB1-mismatched, but the mechanisms leading to GVHD are unknown. The HLA-DPB1 regulatory region variant rs9277534 is associated with HLA-DPB1 expression. We tested the hypothesis that the GVHD risk correlates with the rs9277534 allele linked to the mismatched HLA-DPB1 in the recipient. METHODS We genotyped rs9277534 in 3505 persons to define rs9277534-DPB1 haplotypes. Among 1441 recipients of transplants from HLA-A,B,C,DRB1,DQB1-matched unrelated donors with only one HLA-DPB1 mismatch, linkage of the rs9277534 A and G alleles to the mismatched HLA-DPB1 was determined. HLA-DPB1 expression was assessed by means of a quantitative polymerase-chain-reaction assay. The risk of acute GVHD among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534G (high expression) was compared with the risk among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534A (low expression). RESULTS The mean HLA-DPB1 expression was lower with rs9277534A than with rs9277534G. Among recipients of transplants from donors with rs9277534A-linked HLA-DPB1, the risk of acute GVHD was higher for recipients with rs9277534G-linked HLA-DPB1 mismatches than for recipients with rs9277534A-linked HLA-DPB1 mismatches (hazard ratio, 1.54; 95% confidence interval [CI], 1.25 to 1.89; P<0.001), as was the risk of death due to causes other than disease recurrence (hazard ratio, 1.25; 95% CI, 1.00 to 1.57; P = 0.05). CONCLUSIONS The risk of GVHD associated with HLA-DPB1 mismatching was influenced by the HLA-DPB1 rs9277534 expression marker. Among recipients of HLA-DPB1-mismatched transplants from donors with the low-expression allele, recipients with the high-expression allele had a high risk of GVHD. (Funded by the National Institutes of Health and others.) C1 [Petersdorf, Effie W.; Malkki, Mari; Gooley, Ted; Stevenson, Philip] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Petersdorf, Effie W.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [O'hUigin, Colm; Carrington, Mary] Frederick Natl Labs Canc Res, Leidos Biomed Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. [Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Carrington, Mary] Harvard Univ, Boston, MA 02115 USA. [Haagenson, Michael D.; Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Horowitz, Mary M.; Wang, Tao] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. RP Petersdorf, EW (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, D4-115,1100 Fairview Ave N, Seattle, WA 98109 USA. EM epetersd@fredhutch.org FU National Institutes of Health FX Funded by the National Institutes of Health and others. NR 29 TC 31 Z9 31 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 13 PY 2015 VL 373 IS 7 BP 599 EP 609 DI 10.1056/NEJMoa1500140 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CP2LE UT WOS:000359707700005 PM 26267621 ER PT J AU Lonial, S Dimopoulos, M Palumbo, A White, D Grosicki, S Spicka, I Walter-Croneck, A Moreau, P Mateos, MV Magen, H Belch, A Reece, D Beksac, M Spencer, A Oakervee, H Orlowski, RZ Taniwaki, M Rollig, C Einsele, H Wu, KL Singhal, A San-Miguel, J Matsumoto, M Katz, J Bleickardt, E Poulart, V Anderson, KC Richardson, P AF Lonial, Sagar Dimopoulos, Meletios Palumbo, Antonio White, Darrell Grosicki, Sebastian Spicka, Ivan Walter-Croneck, Adam Moreau, Philippe Mateos, Maria-Victoria Magen, Hila Belch, Andrew Reece, Donna Beksac, Meral Spencer, Andrew Oakervee, Heather Orlowski, Robert Z. Taniwaki, Masafumi Roellig, Christoph Einsele, Hermann Wu, Ka Lung Singhal, Anil San-Miguel, Jesus Matsumoto, Morio Katz, Jessica Bleickardt, Eric Poulart, Valerie Anderson, Kenneth C. Richardson, Paul CA ELOQUENT-2 Investigators TI Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MONOCLONAL-ANTIBODY; SERUM-PROTEIN; ELECTROPHORESIS; DEXAMETHASONE; LENALIDOMIDE; INTERFERENCE; CYTOTOXICITY; CS1 AB BACKGROUND Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma. METHODS In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival. RESULTS Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients. CONCLUSIONS Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797.) C1 [Lonial, Sagar] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA. [Dimopoulos, Meletios] Univ Athens, Athens, Greece. [Palumbo, Antonio] AOU San Giovanni Battista Torino Osped Molinette, Turin, Italy. [White, Darrell] QEII Hlth Sci Ctr, Halifax, NS, Canada. [White, Darrell] Dalhousie Univ, Halifax, NS, Canada. [Belch, Andrew] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Belch, Andrew] Univ Alberta, Edmonton, AB, Canada. [Reece, Donna] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Grosicki, Sebastian] Silesian Med Univ, Katowice, Poland. [Walter-Croneck, Adam] Med Univ Lublin, Lublin, Poland. [Spicka, Ivan] Charles Univ Hosp, Prague, Czech Republic. [Moreau, Philippe] Univ Hosp, Nantes, France. [Mateos, Maria-Victoria] Complejo Asistencial Univ Salamanca, Inst Invest Biomed Salamanca, Salamanca, Spain. [San-Miguel, Jesus] Univ Navarra Clin, Ctr Invest Med Aplicada, Inst Invest Sanitaria Navarra, Pamplona, Spain. [Magen, Hila] Rabin Med Ctr, Davidoff Canc Ctr, Petah Tiqwa, Israel. [Magen, Hila] Tel Aviv Univ, Ramat Aviv, Israel. [Beksac, Meral] Ankara Univ, TR-06100 Ankara, Turkey. [Spencer, Andrew] Monash Univ, Alfred Health, Melbourne, Vic 3004, Australia. [Oakervee, Heather] Barts & London NHS Trust, London, England. [Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Taniwaki, Masafumi] Kyoto Prefectural Univ Med, Kyoto, Japan. [Matsumoto, Morio] Nishigunma Natl Hosp, Shibukawa, Japan. [Roellig, Christoph] Tech Univ Dresden, Univ Klinikum, D-01062 Dresden, Germany. [Einsele, Hermann] Univ Klinikum Wurzburg, Wurzburg, Germany. [Wu, Ka Lung] Zeikenhuis Netwerk Antwerpen, Antwerp, Belgium. [Singhal, Anil] AbbVie Biotherapeut, Redwood City, CA USA. [Katz, Jessica] Bristol Myers Squibb Co, Princeton, NJ USA. [Anderson, Kenneth C.; Richardson, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lonial, S (reprint author), Emory Univ, Sch Med, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. EM sloni01@emory.edu RI richard, chrystelle/K-8595-2015 FU Bristol-Myers Squibb; AbbVie Biotherapeutics FX Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797. NR 15 TC 177 Z9 180 U1 8 U2 25 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 AUG 13 PY 2015 VL 373 IS 7 BP 621 EP 631 DI 10.1056/NEJMoa1505654 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CP2LE UT WOS:000359707700007 PM 26035255 ER PT J AU Moskowitz, SM Shailam, R Mark, EJ AF Moskowitz, Samuel M. Shailam, Randheer Mark, Eugene J. TI Case 25-2015: An 8-Year-Old Girl with a Chest-Wall Mass and a Pleural Effusion SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PULMONARY ACTINOMYCOSIS; EMPYEMA-NECESSITATIS; ACTINOMYCETEMCOMITANS; LYMPHOMA C1 [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Shailam, Randheer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Shailam, Randheer] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Moskowitz, SM (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. FU Vertex Pharmaceuticals; EnBiotix; MCIC Vermont; Kala Pharmaceuticals; Pfizer; Cowen Group; Gilead Sciences; Novartis; Rempex Pharmaceuticals; Savara Pharmaceuticals FX Dr. Moskowitz reports receiving fees for serving on advisory boards from Vertex Pharmaceuticals; consulting fees from EnBiotix, MCIC Vermont, Kala Pharmaceuticals, Pfizer, and Cowen Group; and grant support from Gilead Sciences, Novartis, Rempex Pharmaceuticals, Kala Pharmaceuticals, Vertex Pharmaceuticals, and Savara Pharmaceuticals; as well as holding a pending patent for intermediate-metabolism products that potentiate aminoglycoside antibiotics in bacterial infections (U.S. application number, 61,871,554). Dr. Mark reports providing expert testimony in litigation regarding asbestos exposure. No other potential conflict of interest relevant to this article was reported. NR 17 TC 1 Z9 1 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 AUG 13 PY 2015 VL 373 IS 7 BP 657 EP 667 DI 10.1056/NEJMcpc1400836 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CP2LE UT WOS:000359707700011 PM 26267626 ER PT J AU Zhang, XL Tian, YL Zhang, HB Kavishwar, A Lynes, M Brownell, AL Sun, HB Tseng, YH Moore, A Ran, CZ AF Zhang, Xueli Tian, Yanli Zhang, Hongbin Kavishwar, Amol Lynes, Matthew Brownell, Anna-Liisa Sun, Hongbin Tseng, Yu-Hua Moore, Anna Ran, Chongzhao TI Curcumin analogues as selective fluorescence imaging probes for brown adipose tissue and monitoring browning SO SCIENTIFIC REPORTS LA English DT Article ID CHAIN FATTY-ACIDS; ADULT HUMANS; WHITE FAT; RECEPTOR ACTIVATION; ENERGY-EXPENDITURE; MEMBRANE-PROTEINS; BEIGE ADIPOCYTES; F-18-FDG PET/CT; SKELETAL-MUSCLE; LIPID DROPLETS AB Manipulation of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can be promising new approaches to counter metabolic disorder diseases in humans. Imaging probes that could consistently monitor BAT mass and browning of WAT are highly desirable. In the course of our imaging probe screening, we found that BAT could be imaged with curcumin analogues in mice. However, the poor BAT selectivity over WAT and short emissions of the lead probes promoted further lead optimization. Limited uptake mechanism studies suggested that CD36/FAT (fatty acid transporter) probably contributed to the facilitated uptake of the probes. By increasing the stereo-hindrance of the lead compound, we designed CRANAD-29 to extend the emission and increase the facilitated uptake, thus increasing its BAT selectivity. Our data demonstrated that CRANAD-29 had significantly improved selectivity for BAT over WAT, and could be used for imaging BAT mass change in a streptozotocin-induced diabetic mouse model, as well as for monitoring BAT activation under cold exposure. In addition, CRANAD-29 could be used for monitoring the browning of subcutaneous WAT (sWAT) induced by beta 3-adrenoceptor agonist CL-316, 243. C1 [Zhang, Xueli; Tian, Yanli; Kavishwar, Amol; Brownell, Anna-Liisa; Moore, Anna; Ran, Chongzhao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Mol Imagi, Boston, MA 02215 USA. [Zhang, Xueli; Sun, Hongbin] China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China. [Zhang, Xueli] Southeast Univ, ZhongDa Hosp, Dept Pharm, Nanjing 210009, Jiangsu, Peoples R China. [Tian, Yanli] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510275, Guangdong, Peoples R China. [Zhang, Hongbin; Lynes, Matthew; Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Zhang, Hongbin; Lynes, Matthew; Tseng, Yu-Hua] Harvard Stem Cell Inst, Boston, MA 02215 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Mol Imagi, Boston, MA 02215 USA. EM amoore@helix.mgh.harvard.edu; cran@nmr.mgh.harvard.edu OI Kavishwar, Amol/0000-0001-8214-6625 FU China Scholarship Council of Ministry of Education of China FX We thank Pamela Pantazopoulos, B.S., and Alana Ross, B.S. for proofreading this manuscript. We also thank China Scholarship Council of Ministry of Education of China for supporting (X.Z. and Y.T.). NR 89 TC 2 Z9 2 U1 7 U2 35 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 AUG 13 PY 2015 VL 5 AR 13116 DI 10.1038/srep13116 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO8GT UT WOS:000359405900001 PM 26269357 ER PT J AU Zhang, SF Ermann, J Succi, MD Zhou, A Hamilton, MJ Cao, BN Korzenik, JR Glickman, JN Vemula, PK Glimcher, LH Traverso, G Langer, R Karp, JM AF Zhang, Sufeng Ermann, Joerg Succi, Marc D. Zhou, Allen Hamilton, Matthew J. Cao, Bonnie Korzenik, Joshua R. Glickman, Jonathan N. Vemula, Praveen K. Glimcher, Laurie H. Traverso, Giovanni Langer, Robert Karp, Jeffrey M. TI An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID NEGATIVELY CHARGED LIPOSOMES; QUALITY-OF-LIFE; ULCERATIVE-COLITIS; COLONIC-MUCOSA; BIODEGRADABLE PARTICLES; GLUCOCORTICOID-RECEPTOR; INCREASING PROTEIN; GENE-EXPRESSION; IN-VITRO; NANOPARTICLES AB There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD. C1 [Zhang, Sufeng; Succi, Marc D.; Traverso, Giovanni; Langer, Robert; Karp, Jeffrey M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Zhang, Sufeng; Succi, Marc D.; Zhou, Allen; Karp, Jeffrey M.] Brigham & Womens Hosp, Ctr Regenerat Therapeut, Biomed Res Inst, Boston, MA 02115 USA. [Zhang, Sufeng; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Ermann, Joerg] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Ermann, Joerg; Succi, Marc D.; Hamilton, Matthew J.; Korzenik, Joshua R.; Glickman, Jonathan N.; Traverso, Giovanni; Karp, Jeffrey M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hamilton, Matthew J.; Cao, Bonnie; Korzenik, Joshua R.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Glickman, Jonathan N.] Miraca Life Sci, Newton, MA 02464 USA. [Vemula, Praveen K.] Inst Stem Cell Biol & Regenerat Med inStem, Bangalore 560065, Karnataka, India. [Glimcher, Laurie H.] Weill Cornell Med Coll, New York, NY 10065 USA. [Traverso, Giovanni] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Langer, Robert; Karp, Jeffrey M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Karp, Jeffrey M.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Traverso, G (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ctraverso@partners.org; rlanger@mit.edu; jmkarp@partners.org FU Natural Sciences and Engineering Research Council of Canada; Department of Biotechnology, India; Harvard Institute of Translational Immunology/Helmsley Trust Pilot Grants in Crohn's Disease; NIH [CA112663, T32DK7191-38-S1, DE013023, EB000244, DE023432, AR063866]; Max Planck Research Award from the Alexander von Humboldt Foundation FX Funding: S.Z. received a fellowship from the Natural Sciences and Engineering Research Council of Canada. P.K.V. received a Ramalingaswami Re-entry Fellowship from the Department of Biotechnology, India. This work was supported by Harvard Institute of Translational Immunology/Helmsley Trust Pilot Grants in Crohn's Disease to J.E., L.H.G., and J.M.K.; NIH grant CA112663 to L.H.G.; NIH grant T32DK7191-38-S1 to G.T.; NIH grants DE013023 and EB000244 and a Max Planck Research Award from the Alexander von Humboldt Foundation to R.L.; and NIH grants DE023432 and AR063866 to J.M.K. NR 40 TC 10 Z9 10 U1 13 U2 51 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD AUG 12 PY 2015 VL 7 IS 300 AR 300ra128 DI 10.1126/scitranslmed.aaa5657 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CQ9NA UT WOS:000360940600005 PM 26268315 ER PT J AU Lemon, CM Karnas, E Han, XX Bruns, OT Kempa, TJ Fukumura, D Bawendi, MG Jain, RK Duda, DG Nocera, DG AF Lemon, Christopher M. Karnas, Elizabeth Han, Xiaoxing Bruns, Oliver T. Kempa, Thomas J. Fukumura, Dai Bawendi, Moungi G. Jain, Rakesh K. Duda, Dan G. Nocera, Daniel G. TI Micelle-Encapsulated Quantum Dot-Porphyrin Assemblies as in Vivo Two-Photon Oxygen Sensors SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ABSORPTION CROSS-SECTION; TUMOR MICROENVIRONMENT; PHOSPHOLIPID MICELLES; RIBONUCLEOTIDE REDUCTASE; FLUORESCENCE EXCITATION; PHOTODYNAMIC THERAPY; OPTICAL-PROPERTIES; ENERGY-TRANSFER; BLOOD-FLOW; PH SENSOR AB Micelles have been employed to encapsulate the supramolecular assembly of quantum dots with palladium(II) porphyrins for the quantification of O-2 levels in aqueous media and in vivo. Forster resonance energy transfer from the quantum dot (QD) to the palladium porphyrin provides a means for signal transduction under both one- and two-photon excitation. The palladium porphyrins are sensitive to O-2 concentrations in the range of 0-160 Torr. The micelle-encapsulated QD-porphyrin assemblies have been employed for in vivo multiphoton imaging and lifetime-based oxygen measurements in mice with chronic dorsal skinfold chambers or cranial windows. Our results establish the utility of the QD-micelle approach for in vivo biological sensing applications. C1 [Lemon, Christopher M.; Kempa, Thomas J.; Nocera, Daniel G.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Lemon, Christopher M.; Karnas, Elizabeth; Bruns, Oliver T.; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Han, Xiaoxing; Fukumura, Dai; Jain, Rakesh K.; Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Han, Xiaoxing; Fukumura, Dai; Jain, Rakesh K.; Duda, Dan G.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu; mgb@mit.edu; jain@steele.mgh.harvard.edu; dan@steele.mgh.harvard.edu; dnocera@fas.harvad.edu RI Bruns, Oliver/D-6735-2015 OI Bruns, Oliver/0000-0002-5738-0126 FU U.S. National Cancer Institute [R01-CA126642]; ISN ARO [W911NF-07-D-0004]; U.S. Department of Energy Office of Science, Office of Basic Energy Sciences [DE-SC0009758]; National Science Foundation (NSF) FX We thank Dr. Dilek Dogutan for helpful synthetic discussions and Andrew Maher for assistance with experiments using the Libra-F-HE laser system. This research was supported by the U.S. National Cancer Institute grant R01-CA126642, the ISN ARO W911NF-07-D-0004, and the U.S. Department of Energy Office of Science, Office of Basic Energy Sciences under award no. DE-SC0009758. C.M.L. acknowledges the National Science Foundation (NSF) for a Graduate Research Fellowship Program (GRFP) Fellowship. NR 99 TC 17 Z9 17 U1 29 U2 158 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 12 PY 2015 VL 137 IS 31 BP 9832 EP 9842 DI 10.1021/jacs.5b04765 PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA CP1CK UT WOS:000359613300018 PM 26149349 ER PT J AU Alawieh, A Elvington, A Tomlinson, S AF Alawieh, Ali Elvington, Andrew Tomlinson, Stephen TI Complement in the homeostatic and ischemic brain SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE complement; stroke; innate immunity; neuroprotection; brain ischemia; reperfusion injury ID MANNOSE-BINDING LECTIN; CENTRAL-NERVOUS-SYSTEM; FOCAL CEREBRAL-ISCHEMIA; C-REACTIVE PROTEIN; ANAPHYLATOXIN C5A NEUROPROTECTS; TISSUE-PLASMINOGEN ACTIVATOR; MEMBRANE ATTACK COMPLEX; NONHUMAN PRIMATE MODEL; APOPTOTIC CELL-DEATH; REPERFUSION INJURY AB The complement system is a component of the immune system involved in both recognition and response to pathogens, and it is implicated in an increasing number of homeostatic and disease processes. It is well documented that reperfusion of ischemic tissue results in complement activation and an inflammatory response that causes post-reperfusion injury. This occurs following cerebral ischemia and reperfusion and triggers secondary damage that extends beyond the initial infarcted area, an outcome that has rationalized the use of complement inhibitors as candidate therapeutics after stroke. In the central nervous system, however, recent studies have revealed that complement also has essential roles in synaptic pruning, neurogenesis, and neuronal migration. In the context of recovery after stroke, these apparent divergent functions of complement may account for findings that the protective effect of complement inhibition in the acute phase after stroke is not always maintained in the subacute and chronic phases. The development of effective stroke therapies based on modulation of the complement system will require a detailed understanding of complement-dependent processes in both early neurodegenerative events and delayed neuro-reparatory processes. Here, we review the role of complement in normal brain physiology, the events initiating complement activation after cerebral ischemia-reperfusion injury, and the contribution of complement to both injury and recovery. We also discuss how the design of future experiments may better characterize the dual role of complement in recovery after ischemic stroke. C1 [Alawieh, Ali] Med Univ S Carolina, Neurosci Inst, Dept Neurosci, Charleston, SC 29425 USA. [Elvington, Andrew] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave,BSB 203,MSC 504, Charleston, SC 29425 USA. EM tomlinss@musc.edu OI Alawieh, Ali/0000-0003-2601-8850 FU Veterans Affairs [RX001141, BX001201]; NIH [P20GM109040] FX ST is supported by grants from Veterans Affairs (RX001141 and BX001201) and the NIH (P20GM109040). NR 130 TC 8 Z9 10 U1 0 U2 7 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD AUG 12 PY 2015 VL 6 BP 1 EP 18 AR 417 DI 10.3389/fimmu.2015.00417 PG 18 WC Immunology SC Immunology GA CO9DM UT WOS:000359472900001 PM 26322048 ER PT J AU Chow, PM Chiang, IN Chen, CY Huang, KH Hsu, JS Wang, SM Lee, YJ Yu, HJ Pu, YS Huang, CY AF Chow, Po-Ming Chiang, I-Ni Chen, Chia-Yen Huang, Kuo-How Hsu, Jui-Shan Wang, Shuo-Meng Lee, Yuan-Ju Yu, Hong-Jeng Pu, Yeong-Shiau Huang, Chao-Yuan TI Malignant Ureteral Obstruction: Functional Duration of Metallic versus Polymeric Ureteral Stents SO PLOS ONE LA English DT Article ID INITIAL-EXPERIENCE; MANAGEMENT AB Background Ureteral obstruction caused by extrinsic compression is often associated with intra-abdominal cancers. Internal drainage with ureteral stents is typically the first-line therapy to relieve such obstructions. Novel designs of ureteral stents made of different materials have been invented to achieve better drainage. In this study, we described the functional outcomes of a Resonance metallic ureteral stent (Cook Medical, Bloomington, Indiana, USA) in patients with malignant ureteral obstruction and compare the functional duration of Resonance stents with regular polymeric stents in the same cohort. Methods Cancer patients who received polymeric stents and subsequent Resonance stents for ureteral obstruction between July 2009 and November 2012 were included in a chart review. Stent failure was detected by clinical symptoms, imaging studies, and renal function tests. The functional durations of each stent were calculated, and possible factors affecting stent patency were investigated. Results A total of 50 stents were successfully inserted into 50 ureteral units in 42 patients with malignant ureteral obstruction. There were 7 antegrade stents and 43 retrograde stents. There were no major complications. Stent-related symptoms were similar in both kinds of stents. After polymeric stents were replaced with Resonance metallic stents, hydronephrosis subsided or remained stable in 90% (45/50) of the ureteral units. Serum creatinine decreased or remained stable in 90% (38/42) of these patients. The Resonance stent exhibited a mean increase in functional duration of 4 months compared with the polymeric stents (p<0.0001), and 50% (25/50) of the Resonance stents exhibited a significant increase in functional duration ( more than 3 months). Pre-operative serum creatinine < 2 was associated with a substantial increase in stent duration. Conclusions Resonance stents are effective and safe in relieving malignant ureteral obstructions after polymeric stents failure. Resonance stents can provide a longer functional duration than polymeric stents and should be offered as an option for internal drainage. C1 [Chow, Po-Ming; Chiang, I-Ni; Huang, Kuo-How; Wang, Shuo-Meng; Lee, Yuan-Ju; Yu, Hong-Jeng; Pu, Yeong-Shiau; Huang, Chao-Yuan] Natl Taiwan Univ Hosp, Dept Urol, Taipei, Taiwan. [Chow, Po-Ming; Chiang, I-Ni; Huang, Kuo-How; Hsu, Jui-Shan; Wang, Shuo-Meng; Lee, Yuan-Ju; Yu, Hong-Jeng; Pu, Yeong-Shiau; Huang, Chao-Yuan] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Chen, Chia-Yen] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Chen, Chia-Yen] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Hsu, Jui-Shan] Fu Jen Catholic Univ, Sch Med, Cardinal Tien Hosp, Dept Med Imaging, New Taipei City, Taiwan. [Hsu, Jui-Shan] Natl Taiwan Univ, Dept Med Imaging, Taipei 10764, Taiwan. RP Huang, CY (reprint author), Natl Taiwan Univ Hosp, Dept Urol, Taipei, Taiwan. EM cyh540909@gmail.com OI HUANG, CHAO-YUAN/0000-0002-9322-6062; PU, YEONG-SHIAU/0000-0002-2859-3966 NR 22 TC 3 Z9 3 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 12 PY 2015 VL 10 IS 8 AR e0135566 DI 10.1371/journal.pone.0135566 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO9JT UT WOS:000359492300135 PM 26267140 ER PT J AU Raina, D Agarwal, P Lee, J Bharti, A McKnight, CJ Sharma, P Kharbanda, S Kufe, D AF Raina, Deepak Agarwal, Praveen Lee, James Bharti, Ajit McKnight, C. James Sharma, Pankaj Kharbanda, Surender Kufe, Donald TI Characterization of the MUC1-C Cytoplasmic Domain as a Cancer Target SO PLOS ONE LA English DT Article ID CELL LUNG-CANCER; TRANSCRIPTION FACTOR; INTRINSIC DISORDER; REGULATORY LOOP; ONCOPROTEIN; ACTIVATION; SURVIVAL; PREDICTION AB Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly expressed in diverse human carcinomas and certain hematologic malignancies. The oncogenic MUC1 transmembrane C-terminal subunit (MUC1-C) functions in part by transducing growth and survival signals from cell surface receptors. However, little is known about the structure of the MUC1-C cytoplasmic domain as a potential drug target. Using methods for structural predictions, our results indicate that a highly conserved CQCRRK sequence, which is adjacent to the cell membrane, forms a small pocket that exposes the two cysteine residues for forming disulfide bonds. By contrast, the remainder of the MUC1-C cytoplasmic domain has no apparent structure, consistent with an intrinsically disordered protein. Our studies thus focused on targeting the MUC1 CQCRRK region. The results show that L-and D-amino acid CQCRRK-containing peptides bind directly to the CQC motif. We further show that the D-amino acid peptide, designated GO-203, blocks homodimerization of the MUC1-C cytoplasmic domain in vitro and in transfected cells. Moreover, GO-203 binds directly to endogenous MUC1-C in breast and lung cancer cells. Colocalization studies further demonstrate that GO-203 predominantly binds to MUC1-C at the cell membrane. These findings support the further development of agents that target the MUC1-C cytoplasmic domain CQC motif and thereby MUC1-C function in cancer cells. C1 [Raina, Deepak; Lee, James; Kharbanda, Surender; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Raina, Deepak; Kharbanda, Surender] Genus Oncol, Boston, MA 02118 USA. [Agarwal, Praveen; Sharma, Pankaj] LeadInvent, New Delhi, India. [Bharti, Ajit] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [McKnight, C. James] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. EM donald_kufe@dfci.harvard.edu FU National Cancer Institute of the National Institutes of Health [CA097098, CA166480]; Genus Oncology; LeadInvent FX Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under awards CA097098 and CA166480, http://www.cancer.gov (D.K.). Genus Oncology provided support in the form of salaries for authors D.R. and S.K. LeadInvent provided support in the form of salaries for authors P.A. and P.S. The specific roles of these authors are articulated in the "authors contributions section". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 10 Z9 11 U1 1 U2 7 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 AUG 12 PY 2015 VL 10 IS 8 AR e0135156 DI 10.1371/journal.pone.0135156 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO9JT UT WOS:000359492300084 PM 26267657 ER PT J AU Scirica, BM Braunwald, E Raz, I Cavender, MA Morrow, DA Jarolim, P Udell, JA Mosenzon, O Im, K Umez-Eronini, AA Pollack, PS Hirshberg, B Frederich, R Lewis, BS McGuire, DK Davidson, J Steg, G Bhatt, DL AF Scirica, Benjamin M. Braunwald, Eugene Raz, Itamar Cavender, Matthew A. Morrow, David A. Jarolim, Petr Udell, Jacob A. Mosenzon, Ofri Im, KyungAh Umez-Eronini, Amarachi A. Pollack, Pia S. Hirshberg, Boaz Frederich, Robert Lewis, Basil S. McGuire, Darren K. Davidson, Jaime Steg, Gabriel Bhatt, Deepak L. TI Heart Failure, Saxagliptin and Diabetes Mellitus: Observations From the SAVOR-TIMI 53 Randomized Trial Response SO CIRCULATION LA English DT Letter ID ANGIOTENSIN-CONVERTING ENZYME; INHIBITION C1 [Scirica, Benjamin M.; Braunwald, Eugene; Cavender, Matthew A.; Morrow, David A.; Im, KyungAh; Umez-Eronini, Amarachi A.; Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Raz, Itamar; Mosenzon, Ofri] Hadassah Hebrew Univ Hosp, Div Internal Med, Diabet Unit, Jerusalem, Israel. [Jarolim, Petr] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Udell, Jacob A.] Univ Toronto, Cardiovasc Div, Womens Coll Hosp, Toronto, ON, Canada. [Udell, Jacob A.] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada. [Pollack, Pia S.; Hirshberg, Boaz] AstraZeneca Res & Dev, Wilmington, DE USA. [Frederich, Robert] Bristol Myers Squibb, Princeton, NJ USA. [Lewis, Basil S.] Technion Israel Inst Technol, Cardiovasc Res Inst, Lady Davis Carmel Med Ctr, Haifa, Israel. [Lewis, Basil S.] Technion Israel Inst Technol, Ruth & Bruce Rappaport Sch Med, Haifa, Israel. [McGuire, Darren K.] Univ Texas SW Med Ctr Dallas, Cardiovasc Med, Dept Internal Med, Dallas, TX 75390 USA. [Davidson, Jaime] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Endocrinol, Dallas, TX 75390 USA. [Steg, Gabriel] Univ Paris Diderot, Hop Bichat, AP HP, Dept Hosp Univ FIRE,INSERM,U1148, Paris, France. [Steg, Gabriel] Royal Brompton Hosp, NHLI Imperial Coll, ICMS, London SW3 6LY, England. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 3 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD AUG 11 PY 2015 VL 132 IS 6 BP E121 EP E122 DI 10.1161/CIRCULATIONAHA.115.015511 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP1WD UT WOS:000359666700016 PM 26260506 ER PT J AU Salam, MT Avoundjian, T Knight, WM Gilliland, FD AF Salam, Muhammad T. Avoundjian, Tigran Knight, Wendy M. Gilliland, Frank D. TI Genetic Ancestry and Asthma and Rhinitis Occurrence in Hispanic Children: Findings from the Southern California Children's Health Study SO PLOS ONE LA English DT Article ID MEXICAN-AMERICAN CHILDREN; MULTILOCUS GENOTYPE DATA; CHILDHOOD ASTHMA; ACCULTURATION SCALE; AFRICAN ANCESTRY; UNITED-STATES; RISK-FACTOR; ASSOCIATIONS; BIRTH; SUSCEPTIBILITY AB Background Asthma and rhinitis are common childhood health conditions. Being an understudied and rapidly growing population in the US, Hispanic children have a varying risk for these conditions that may result from sociocultural (including acculturative factors), exposure and genetic diversities. Hispanic populations have varying contributions from European, Amerindian and African ancestries. While previous literature separately reported associations between genetic ancestry and acculturation factors with asthma, whether Amerindian ancestry and acculturative factors have independent associations with development of early-life asthma and rhinitis in Hispanic children remains unknown. We hypothesized that genetic ancestry is an important determinant of early-life asthma and rhinitis occurrence in Hispanic children independent of sociodemographic, acculturation and environmental factors. Methods Subjects were Hispanic children (5-7 years) who participated in the southern California Children's Health Study. Data from birth certificates and questionnaire provided information on acculturation, sociodemographic and environmental factors. Genetic ancestries (Amerindian, European, African and Asian) were estimated based on 233 ancestry informative markers. Asthma was defined by parental report of doctor-diagnosed asthma. Rhinitis was defined by parental report of a history of chronic sneezing or runny or blocked nose without a cold or flu. Sample sizes were 1,719 and 1,788 for investigating the role of genetic ancestry on asthma and rhinitis, respectively. Results Children had major contributions from Amerindian and European ancestries. After accounting for potential confounders, per 25% increase in Amerindian ancestry was associated with 17.6% (95% confidence interval [CI]: 0.74-0.99) and 13.6% (95% CI: 0.79-0.98) lower odds of asthma and rhinitis, respectively. Acculturation was not associated with either outcome. Conclusions Earlier work documented that Hispanic children with significant contribution from African ancestry are at increased asthma risk; however, in Hispanic children who have little contribution from African ancestry, Amerindian ancestry was independently associated with lower odds for development of early-childhood asthma and rhinitis. C1 [Salam, Muhammad T.; Gilliland, Frank D.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Salam, Muhammad T.] Kern Med Ctr, Dept Psychiat, Bakersfield, CA USA. [Avoundjian, Tigran] US Dept Vet Affairs, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Knight, Wendy M.] Los Angeles Cty Dept Publ Hlth, Acute Communicable Dis Control Program, Los Angeles, CA USA. RP Salam, MT (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. EM msalam@usc.edu FU National Heart, Lung and Blood Institute [5R01HL61768, 5R01HL76647]; Southern California Environmental Health Sciences Center - National Institute of Environmental Health Sciences [5P30ES007048]; Children's Environmental Health Center - National Institute of Environmental Health Sciences [5P01ES009581, R826708-01, RD831861-01]; U.S. Environmental Protection Agency; National Institute of Environmental Health Sciences [5P01ES011627]; Hastings Foundation FX This work was supported by the National Heart, Lung and Blood Institute (grants 5R01HL61768 and 5R01HL76647; URL http://www.nhlbi.nih.gov/); the Southern California Environmental Health Sciences Center (grant 5P30ES007048) funded by the National Institute of Environmental Health Sciences; the Children's Environmental Health Center (grants 5P01ES009581, R826708-01, and RD831861-01) funded by the National Institute of Environmental Health Sciences (URL: http://www.niehs.nih.gov/) and the U.S. Environmental Protection Agency (URL: http://www.epa.gov/); the National Institute of Environmental Health Sciences (grants 5P01ES011627; URL: http://www.niehs.nih.gov); and the Hastings Foundation. The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. NR 36 TC 2 Z9 2 U1 1 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 AUG 11 PY 2015 VL 10 IS 8 AR e0135384 DI 10.1371/journal.pone.0135384 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO7PP UT WOS:000359353300078 PM 26263549 ER PT J AU Calligaris, D Feldman, DR Norton, I Olubiyi, O Changelian, AN Machaidze, R Vestal, ML Laws, ER Dunn, IF Santagata, S Agar, NYR AF Calligaris, David Feldman, Daniel R. Norton, Isaiah Olubiyi, Olutayo Changelian, Armen N. Machaidze, Revaz Vestal, Matthew L. Laws, Edward R. Dunn, Ian F. Santagata, Sandro Agar, Nathalie Y. R. TI MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mass spectrometry imaging; pituitary; molecular pathology; intrasurgical diagnosis; in-source decay ID IN-SOURCE DECAY; ASSISTED-LASER-DESORPTION/IONIZATION; CLINICAL-PRACTICE GUIDELINE; CUSHINGS-SYNDROME; CANCER-RESEARCH; MATRIX; PROTEINS; PEPTIDES; DIAGNOSIS; HYPERPROLACTINEMIA AB We present a proof of concept study designed to support the clinical development of mass spectrometry imaging (MSI) for the detection of pituitary tumors during surgery. We analyzed by matrix-assisted laser desorption/ionization (MALDI) MSI six nonpathological (NP) human pituitary glands and 45 hormone secreting and nonsecreting (NS) human pituitary adenomas. We show that the distribution of pituitary hormones such as prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), and thyroid stimulating hormone (TSH) in both normal and tumor tissues can be assessed by using this approach. The presence of most of the pituitary hormones was confirmed by using MS/MS and pseudo-MS/MS methods, and subtyping of pituitary adenomas was performed by using principal component analysis (PCA) and support vector machine (SVM). Our proof of concept study demonstrates that MALDI MSI could be used to directly detect excessive hormonal production from functional pituitary adenomas and generally classify pituitary adenomas by using statistical and machine learning analyses. The tissue characterization can be completed in fewer than 30 min and could therefore be applied for the near-real-time detection and delineation of pituitary tumors for intra-operative surgical decision-making. C1 [Calligaris, David; Feldman, Daniel R.; Norton, Isaiah; Olubiyi, Olutayo; Changelian, Armen N.; Machaidze, Revaz; Vestal, Matthew L.; Laws, Edward R.; Dunn, Ian F.; Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Machaidze, Revaz; Santagata, Sandro] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Santagata, Sandro; Agar, Nathalie Y. R.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Agar, NYR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. EM nathalie_agar@dfci.harvard.edu OI OLUBIYI, OLUTAYO/0000-0002-2803-3686 FU National Institute of Health (NIH) Director's New Innovator Award [1DP2OD007383-01]; US Army Medical Research/Center for Integration of Medicine and Innovative Technology (CIMIT) Grant [2010A052245]; National Center for Image Guided Therapy [P41RR019703]; NIH [K08NS064168]; Pediatric Low Grade Astrocytoma Program at Dana-Farber Cancer Institute; Brain Science Foundation; Daniel E. Ponton fund for the Neurosciences at Brigham and Women's Hospital (BWH) FX This work was funded in part by National Institute of Health (NIH) Director's New Innovator Award 1DP2OD007383-01 (to N.Y.R.A.); US Army Medical Research/Center for Integration of Medicine and Innovative Technology (CIMIT) Grant 2010A052245; the National Center for Image Guided Therapy Grant P41RR019703; NIH Grant K08NS064168 (to S.S.); Pediatric Low Grade Astrocytoma Program at Dana-Farber Cancer Institute; the Brain Science Foundation; and the Daniel E. Ponton fund for the Neurosciences at Brigham and Women's Hospital (BWH). NR 57 TC 6 Z9 6 U1 4 U2 23 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 AUG 11 PY 2015 VL 112 IS 32 BP 9978 EP 9983 DI 10.1073/pnas.1423101112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO6RY UT WOS:000359285100063 PM 26216958 ER PT J AU Di Caprio, G Stokes, C Higgins, JM Schonbrun, E AF Di Caprio, Giuseppe Stokes, Chris Higgins, John M. Schonbrun, Ethan TI Single-cell measurement of red blood cell oxygen affinity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hematology; medical sciences; flow cytometry; organ on chip; single-cell variability ID IN-VIVO; HEMOGLOBIN; MICROSCOPY; VOLUME; ERYTHROCYTES; TISSUES; PHASE; CHIP AB Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume, and Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen-Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2-3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability. C1 [Di Caprio, Giuseppe; Stokes, Chris; Schonbrun, Ethan] Harvard Univ, Rowland Inst, Cambridge, MA 02142 USA. [Higgins, John M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02115 USA. [Higgins, John M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Di Caprio, G (reprint author), Harvard Univ, Rowland Inst, Cambridge, MA 02142 USA. EM dicaprio@rowland.harvard.edu FU NHLBI NIH HHS [U01 HL114476]; NIDDK NIH HHS [DP2 DK098087] NR 32 TC 1 Z9 1 U1 6 U2 22 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 AUG 11 PY 2015 VL 112 IS 32 BP 9984 EP 9989 DI 10.1073/pnas.1509252112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO6RY UT WOS:000359285100064 PM 26216973 ER PT J AU Spielberg, JM Miller, GA Heller, W Banich, MT AF Spielberg, Jeffrey M. Miller, Gregory A. Heller, Wendy Banich, Marie T. TI Flexible brain network reconfiguration supporting inhibitory control SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE inhibitory control; inhibition; brain network; graph theory; dorsal anterior cingulate ID ANTERIOR CINGULATE CORTEX; INFERIOR FRONTAL-CORTEX; PREFRONTAL CORTEX; COGNITIVE CONTROL; RESPONSE-INHIBITION; FUNCTIONAL CONNECTIVITY; STROOP TASK; EXECUTIVE FUNCTION; METAANALYSIS; MECHANISMS AB The ability to inhibit distracting stimuli from interfering with goaldirected behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory tools to functionalmagnetic resonance imaging data collected while a large sample of adults (n = 101) performed a color-word Stroop task. Higher demand for inhibitory control was associated with restructuring of the global network into a configuration that was more optimized for specialized processing (functional segregation), more efficient at communicating the output of such processing across the network (functional integration), and more resilient to potential interruption (resilience). In addition, there were regional changes with right inferior frontal sulcus and right anterior insula occupying more central positions as network hubs, and dorsal anterior cingulate cortex becoming more tightly coupled with its regional subnetwork. Given the crucial role of inhibitory control in goal-directed behavior, present findings identifying functional network organization supporting inhibitory control have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties. C1 [Spielberg, Jeffrey M.] Vet Affairs Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA 02130 USA. [Spielberg, Jeffrey M.] Boston Univ Sch Med, Dept Psychiat, Boston, MA 02130 USA. [Miller, Gregory A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Miller, Gregory A.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Heller, Wendy] Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. [Banich, Marie T.] Univ Colorado, Dept Psychol, Inst Cognit Sci, Boulder, CO 80309 USA. [Banich, Marie T.] Univ Colorado, Dept Neurosci, Inst Cognit Sci, Boulder, CO 80309 USA. RP Spielberg, JM (reprint author), Vet Affairs Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA 02130 USA. EM jspielb2@gmail.com FU National Institute of Mental Health [P50 MH079485, R01 MH61358] FX This work was supported by National Institute of Mental Health Grants P50 MH079485 and R01 MH61358. NR 46 TC 6 Z9 6 U1 2 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 11 PY 2015 VL 112 IS 32 BP 10020 EP 10025 DI 10.1073/pnas.1500048112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO6RY UT WOS:000359285100070 PM 26216985 ER PT J AU Inci, F Filippini, C Baday, M Ozen, MO Calamak, S Durmus, NG Wang, SQ Hanhauser, E Hobbs, KS Juillard, F Kuang, PP Vetter, ML Carocci, M Yamamoto, HS Takagi, Y Yildiz, UH Akin, D Wesemann, DR Singhal, A Yang, PL Nibert, ML Fichorova, RN Lau, DTY Henrich, TJ Kaye, KM Schachter, SC Kuritzkes, DR Steinmetz, LM Gambhir, SS Davis, RW Demirci, U AF Inci, Fatih Filippini, Chiara Baday, Murat Ozen, Mehmet Ozgun Calamak, Semih Durmus, Naside Gozde Wang, ShuQi Hanhauser, Emily Hobbs, Kristen S. Juillard, Franceline Kuang, Ping Ping Vetter, Michael L. Carocci, Margot Yamamoto, Hidemi S. Takagi, Yuko Yildiz, Umit Hakan Akin, Demir Wesemann, Duane R. Singhal, Amit Yang, Priscilla L. Nibert, Max L. Fichorova, Raina N. Lau, Daryl T. -Y. Henrich, Timothy J. Kaye, Kenneth M. Schachter, Steven C. Kuritzkes, Daniel R. Steinmetz, Lars M. Gambhir, Sanjiv S. Davis, Ronald W. Demirci, Utkan TI Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device ((NERD)-R-2) for diagnostics SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nanoparticle; biodetection; point-of-need; label-free; multiple biotargets ID POINT-OF-CARE; SURFACE-PLASMON RESONANCE; EMERGING TECHNOLOGIES; METAL NANOPARTICLES; BIOSENSOR; CHIP; BINDING; ASSAYS; PH; TUBERCULOSIS AB Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device ((NERD)-R-2), which addresses all these impediments on a single platform. The (NERD)-R-2 employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of (NERD)-R-2 is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The (NERD)-R-2's broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients' homes. C1 [Inci, Fatih; Baday, Murat; Ozen, Mehmet Ozgun; Calamak, Semih; Wang, ShuQi; Yildiz, Umit Hakan; Demirci, Utkan] Stanford Univ, Demirci Bioacoust Microelectromech Syst Med BAMM, Canary Ctr Stanford Canc Early Detect, Radiol Dept,Sch Med, Palo Alto, CA 94304 USA. [Filippini, Chiara] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Durmus, Naside Gozde; Davis, Ronald W.] Stanford Univ, Sch Med, Dept Biochem, Palo Alto, CA 94304 USA. [Durmus, Naside Gozde; Steinmetz, Lars M.; Davis, Ronald W.] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. [Wang, ShuQi] Zhejiang Univ, Coll Med, Affiliated Hosp 1, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China. [Wang, ShuQi] Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou 310003, Zhejiang, Peoples R China. [Wang, ShuQi] Zhejiang Univ, Inst Translat Med, Hangzhou 310029, Zhejiang, Peoples R China. [Hanhauser, Emily; Hobbs, Kristen S.; Henrich, Timothy J.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Juillard, Franceline; Kaye, Kenneth M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kuang, Ping Ping; Lau, Daryl T. -Y.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. [Vetter, Michael L.; Carocci, Margot; Takagi, Yuko; Yang, Priscilla L.; Nibert, Max L.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Yamamoto, Hidemi S.; Fichorova, Raina N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Genital Tract Biol,Dept Obstet Gynecol Reprod, Boston, MA 02115 USA. [Akin, Demir; Gambhir, Sanjiv S.] Stanford Univ, Mol Imaging Program Stanford, Ctr Canc Nanotechnol Excellence, Palo Alto, CA 94305 USA. [Akin, Demir; Gambhir, Sanjiv S.] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94304 USA. [Wesemann, Duane R.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wesemann, Duane R.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Singhal, Amit] ASTAR, Singapore Immunol Network, Singapore 138648, Singapore. [Schachter, Steven C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Gambhir, Sanjiv S.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Gambhir, Sanjiv S.] Stanford Univ, Dept Mat Sci & Engn, Stanford, CA 94305 USA. [Gambhir, Sanjiv S.] Stanford Univ, Bio X Program, Stanford, CA 94305 USA. [Demirci, Utkan] Stanford Univ, Dept Elect Engn Courtesy, Stanford, CA 94305 USA. RP Davis, RW (reprint author), Stanford Univ, Sch Med, Dept Biochem, Palo Alto, CA 94304 USA. EM jeanne.thompson@stanford.edu; utkan@stanford.edu FU NIH [R01AI093282, R01AI081534, U54EB15408, R21AI087107, R01AI076442, U54AI057159, 5T32AI007061]; NIH/National Institute of Allergy and Infectious Disease [R01AI076442, R56AI091889, R01AI079085]; NIH/National Cancer Institute [R01CA082036]; Brigham and Women's Hospital; Epilepsy Foundation FX We thank Mehlika Toy for collaboration and discussion in HBV studies; Mark Anthony Lifson and Jaeyong Yang for critical discussions and reviews; and Yusuf Yesil for his help in Fig. 1 and H. Cumhur Tekin for his help in Fig. 2A, schematic. This work was supported by NIH Grants R01AI093282, R01AI081534, U54EB15408, R21AI087107, R01AI076442, and U54AI057159; by NIH/National Institute of Allergy and Infectious Disease Grants R56AI091889, R01AI079085, and R01AI076442; NIH/National Cancer Institute Grant R01CA082036; by the Brigham and Women's Hospital Bright Futures Prize; and by the Epilepsy Foundation Shark Tank Prize. M.L.V. was supported by NIH Grant 5T32AI007061. NR 56 TC 15 Z9 16 U1 7 U2 49 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 AUG 11 PY 2015 VL 112 IS 32 BP E4354 EP E4363 DI 10.1073/pnas.1510824112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO6RY UT WOS:000359285100006 PM 26195743 ER PT J AU Pepin, D Sosulski, A Zhang, LH Wang, D Vathipadiekal, V Hendren, K Coletti, CM Yu, A Castro, CM Birrer, MJ Gao, GP Donahoe, PK AF Pepin, David Sosulski, Amanda Zhang, Lihua Wang, Dan Vathipadiekal, Vinod Hendren, Katherine Coletti, Caroline M. Yu, Aaron Castro, Cesar M. Birrer, Michael J. Gao, Guangping Donahoe, Patricia K. TI AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MIS; anti-Mullerian hormone; ovarian cancer; PDX; AAV9 ID VIRUS-MEDIATED DELIVERY; HUNTINGTONS-DISEASE; IN-VIVO; CELL-LINES; II RECEPTOR; IMMUNE-RESPONSES; MOUSE MODEL; STEM-CELLS; RAT MODEL; EXPRESSION AB To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in vitro and in vivo. To test this novel therapeutic peptide, serous malignant ascites from highly resistant recurrent ovarian cancer patients were isolated and amplified to create low-passage primary cell lines. Purified recombinant LRMIS protein successfully inhibited the growth of cancer spheroids in vitro in a panel of primary cell lines in four of six patients tested. Adeno-associated virus (AAV) -delivered gene therapy has undergone a clinical resurgence with a good safety profile and sustained gene expression. Therefore, AAV9 was used as a single i.p. injection to deliver LRMIS to test its efficacy in inhibiting growth of palpable tumors in patient-derived ovarian cancer xenografts from ascites (PDXa). AAV9-LRMIS monotherapy resulted in elevated and sustained blood concentrations of MIS, which significantly inhibited the growth of three of five lethal chemoresistant serous adenocarcinoma PDXa models without signs of measurable or overt toxicity. Finally, we tested the frequency of MIS type II receptor expression in a tissue microarray of serous ovarian tumors by immunohistochemistry and found that 88% of patients bear tumors that express the receptor. Taken together, these preclinical data suggest that AAV9-LRMIS provides a potentially well-tolerated and effective treatment strategy poised for testing in patients with chemoresistant serous ovarian cancer. C1 [Pepin, David; Sosulski, Amanda; Zhang, Lihua; Hendren, Katherine; Coletti, Caroline M.; Yu, Aaron; Donahoe, Patricia K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs,Dept Surg, Boston, MA 02114 USA. [Wang, Dan; Gao, Guangping] Univ Massachusetts, Sch Med, Gene Therapy Ctr, Worcester, MA 01655 USA. [Vathipadiekal, Vinod; Castro, Cesar M.; Birrer, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gynecol Oncol,Dept Med, Boston, MA 02114 USA. RP Donahoe, PK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs,Dept Surg, Boston, MA 02114 USA. EM pdonahoe@partners.org OI Vathipadiekal, Vinod/0000-0002-8181-6890 FU Ovarian Cancer Research Fund; Sudna Gar Fellowship; Innovation Development Award from Massachusetts General Hospital, Partners Healthcare; Department of Defense Translational Pilot Award [OC110078]; NIH [R01CA17393]; Massachusetts General Hospital Department of Surgery Award FX We thank Dorothy Ndishabandi for help scanning the tissue microarray slides and Jingwen Chen for her instrumental role in coordinating and collecting ascites samples in Interventional Radiology. This study was funded, in part, by an Ann Shreiber Mentored Investigator Grant from the Ovarian Cancer Research Fund (to D.P.); the Sudna Gar Fellowship (to D.P.); an Innovation Development Award from Massachusetts General Hospital, Partners Healthcare (to D.P. and P.K.D.); Department of Defense Translational Pilot Award OC110078 (to P.K.D.); NIH Grant R01CA17393 (to P.K.D.); a Massachusetts General Hospital Department of Surgery Award (to P.K.D.); philanthropy from the Austen Fund, the McBride family, and Commons Development (P.K.D.); and royalties from the use of the Mullerian inhibiting substance ELISA in infertility clinics around the world. NR 78 TC 5 Z9 5 U1 1 U2 7 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 AUG 11 PY 2015 VL 112 IS 32 BP E4418 EP E4427 DI 10.1073/pnas.1510604112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO6RY UT WOS:000359285100013 PM 26216943 ER PT J AU Michel, SG La Muraglia, GM Madariaga, MLL Titus, JS Selig, MK Farkash, EA Allan, JS Anderson, LM Madsen, JC AF Michel, Sebastian G. La Muraglia, Glenn M., II Madariaga, Maria Lucia L. Titus, James S. Selig, Martin K. Farkash, Evan A. Allan, James S. Anderson, Lisa M. Madsen, Joren C. TI Twelve-Hour Hypothermic Machine Perfusion for Donor Heart Preservation Leads to Improved Ultrastructural Characteristics Compared to Conventional Cold Storage SO ANNALS OF TRANSPLANTATION LA English DT Article DE Heart Transplantation; Myocardial Ischemia; Myocardial Reperfusion Injury; Perfusion ID INTERNATIONAL SOCIETY; TRANSPLANTATION; RECOVERY; REGISTRY; TIME AB Background: Hypothermic machine perfusion of donor hearts has the theoretical advantage of continuous aerobic metabolism and washes out toxic metabolic byproducts. Here, we studied the effect of hypothermic machine perfusion on cardiac myocyte integrity when hearts are preserved for longer ischemic times (12 hours). Material/Methods: Pig hearts were harvested and stored in Celsior (R) solution for 12 hours using either conventional cold storage on ice (12 h CS, n=3) or pulsatile perfusion with the Paragonix Sherpa Perfusion (TM) Cardiac Transport System at different flow rates (12 h PP, n=3 or 12 h PP low flow, n=2). After cold preservation, hearts were reperfused using an LV isovolumic Langendorff system. Controls (n=3) were reperfused immediately after organ harvest. Biopsies were taken from the apex of the left ventricle before storage, after storage and after reperfusion to measure ATP and endothelin-1 content in the tissue. TUNEL staining for signs of apoptosis and electron microscopy of the donor hearts were performed. Results: 12 h PP hearts showed significantly more weight gain than 12 h CS and controls after preservation. Pulsatile perfused hearts showed less ATP depletion, lower endothelin-1 levels and less apoptosis after preservation compared to CS. Electron microscopy showed damaged muscle fibers, endothelial cell rupture, and injury of mitochondria in the 12 h CS group, while machine perfusion could preserve the cell structures. Conclusions: Hypothermic machine perfusion of donor hearts can preserve the cell structures better than conventional cold storage in prolonged ischemic times. Hypothermic pulsatile perfusion may therefore enable longer preservation times of donor hearts. Whether this method is able to avoid primary graft failure after orthotopic heart transplantation remains to be evaluated in further studies. C1 [Michel, Sebastian G.; La Muraglia, Glenn M., II; Madariaga, Maria Lucia L.; Allan, James S.; Madsen, Joren C.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Dept Surg, Boston, MA 02114 USA. [Michel, Sebastian G.; La Muraglia, Glenn M., II; Madariaga, Maria Lucia L.; Allan, James S.; Madsen, Joren C.] Harvard Univ, Sch Med, Boston, MA USA. [Michel, Sebastian G.] Univ Munich, Dept Cardiac Surg, Munich, Germany. [Titus, James S.; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. [Selig, Martin K.; Farkash, Evan A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Allan, James S.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. RP Michel, SG (reprint author), Massachusetts Gen Hosp, Ctr Transplantat Sci, Dept Surg, Boston, MA 02114 USA. EM Sebastian.Michel@med.uni-muenchen.de FU Phase I SBIR grant [1R43HL115852-01] FX This work was supported by a Phase I SBIR grant (1R43HL115852-01) awarded to Paragonix Technologies, Inc. NR 16 TC 0 Z9 0 U1 1 U2 1 PU INT SCIENTIFIC LITERATURE, INC PI SMITHTOWN PA 361 FOREST LANE, SMITHTOWN, NY 11787 USA SN 1425-9524 J9 ANN TRANSPL JI Ann. Transpl. PD AUG 11 PY 2015 VL 20 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA CO7VC UT WOS:000359369700001 ER PT J AU Zinn, E Pacouret, S Khaychuk, V Turunen, HT Carvalho, LS Andres-Mateos, E Shah, S Shelke, R Maurer, AC Plovie, E Xiao, R Vandenberghe, LH AF Zinn, Eric Pacouret, Simon Khaychuk, Vadim Turunen, Heikki T. Carvalho, Livia S. Andres-Mateos, Eva Shah, Samiksha Shelke, Rajani Maurer, Anna C. Plovie, Eva Xiao, Ru Vandenberghe, Luk H. TI In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector SO CELL REPORTS LA English DT Article ID ADENOASSOCIATED VIRUS TYPE-2; LEBERS CONGENITAL AMAUROSIS; NEUTRALIZING ANTIBODIES; MAXIMUM-LIKELIHOOD; DIRECTED EVOLUTION; SEQUENCE ALIGNMENT; CLINICAL-TRIAL; SEROTYPE 9; TRANSDUCTION; SELECTION AB Adeno-associated virus (AAV) vectors have emerged as a gene-delivery platform with demonstrated safety and efficacy in a handful of clinical trials for monogenic disorders. However, limitations of the current generation vectors often prevent broader application of AAV gene therapy. Efforts to engineer AAV vectors have been hampered by a limited understanding of the structure-function relationship of the complex multimeric icosahedral architecture of the particle. To develop additional reagents pertinent to further our insight into AAVs, we inferred evolutionary intermediates of the viral capsid using ancestral sequence reconstruction. In-silico-derived sequences were synthesized de novo and characterized for biological properties relevant to clinical applications. This effort led to the generation of nine functional putative ancestral AAVs and the identification of Anc80, the predicted ancestor of the widely studied AAV serotypes 1, 2, 8, and 9, as a highly potent in vivo gene therapy vector for targeting liver, muscle, and retina. C1 [Zinn, Eric; Pacouret, Simon; Khaychuk, Vadim; Turunen, Heikki T.; Carvalho, Livia S.; Andres-Mateos, Eva; Shah, Samiksha; Shelke, Rajani; Maurer, Anna C.; Plovie, Eva; Xiao, Ru; Vandenberghe, Luk H.] Schepens Eye Res Inst, Grousbeck Gene Therapy Ctr, Boston, MA 02114 USA. [Zinn, Eric; Pacouret, Simon; Khaychuk, Vadim; Turunen, Heikki T.; Carvalho, Livia S.; Andres-Mateos, Eva; Shah, Samiksha; Shelke, Rajani; Maurer, Anna C.; Plovie, Eva; Xiao, Ru; Vandenberghe, Luk H.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Zinn, Eric; Pacouret, Simon; Khaychuk, Vadim; Turunen, Heikki T.; Carvalho, Livia S.; Andres-Mateos, Eva; Shah, Samiksha; Shelke, Rajani; Maurer, Anna C.; Plovie, Eva; Xiao, Ru; Vandenberghe, Luk H.] Harvard Univ, Sch Med, Dept Ophthalmol, Ocular Genom Inst, Boston, MA 02114 USA. [Vandenberghe, Luk H.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Vandenberghe, LH (reprint author), Schepens Eye Res Inst, Grousbeck Gene Therapy Ctr, 20 Staniford St, Boston, MA 02114 USA. EM luk_vandenberghe@meei.harvard.edu OI Carvalho, Livia/0000-0002-3909-5778 FU Harvard Medical School Department of Ophthalmology; Mass Eye and Ear; Grousbeck Family Foundation; Candyce Henwood Fund; NIH Common Fund [5DP1EY023177-03]; Research to Prevent Blindness; Foundation Fighting Blindness FX We thank Yang Lin from the MEEI/SERI Gene Transfer Vector Core (http://vector.meei.harvard.edu); James M. Wilson for sharing vector plasmid and rabbit antiserum reagents; George Church, Eric Pierce, Joshua Plotkin, and Jason Comander for discussion; NEPRC staff for support with the primate studies; Sean Gai and Alden Harwood for technical support and computational analysis; Debalina Sarkar for technical assistance with multiplex cytokine analysis; Debby Pheasant (Biophysical Instrumentation Facility, CSBi at MIT) for training and assistance on AUC; and Phil Seifert (SERI Morphology Core). Support for this work comes from The Harvard Medical School Department of Ophthalmology, Mass Eye and Ear, the Grousbeck Family Foundation, the Candyce Henwood Fund, the NIH Common Fund (5DP1EY023177-03), Research to Prevent Blindness, and Foundation Fighting Blindness. L.H.V. and E.Z. are inventors on a patent describing some of the methods and reagents described here. L.H.V. is inventor on several patents on gene therapy technologies. L.H.V. is co-founder, shareholder, and member of the Scientific Advisory Board and a consultant of GenSight Biologics, an ophthalmology gene therapy company. NR 53 TC 17 Z9 17 U1 0 U2 11 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 AUG 11 PY 2015 VL 12 IS 6 BP 1056 EP 1068 DI 10.1016/j.celrep.2015.07.019 PG 13 WC Cell Biology SC Cell Biology GA CO8LW UT WOS:000359421900014 PM 26235624 ER PT J AU Jacobson, CA Freedman, AS AF Jacobson, Caron A. Freedman, Arnold S. TI Rethinking Prognosis and Therapy for Follicular Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; MARROW-TRANSPLANTATION; COUNT PREDICTS; RITUXIMAB; SURVIVAL; RELAPSE; MUTATIONS C1 [Jacobson, Caron A.] Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jacobson, CA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM cajacobson@partners.org NR 22 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2015 VL 33 IS 23 BP 2489 EP U11 DI 10.1200/JCO.2015.62.3256 PG 4 WC Oncology SC Oncology GA CR9DY UT WOS:000361654600003 PM 26169620 ER PT J AU Schnipper, LE Davidson, NE Wollins, DS Tyne, C Blayney, DW Blum, D Dicker, AP Ganz, PA Hoverman, JR Langdon, R Lyman, GH Meropol, NJ Mulvey, T Newcomer, L Peppercorn, J Polite, B Raghavan, D Rossi, G Saltz, L Schrag, D Smith, TJ Yu, PP Hudis, CA Schilsky, RL AF Schnipper, Lowell E. Davidson, Nancy E. Wollins, Dana S. Tyne, Courtney Blayney, Douglas W. Blum, Diane Dicker, Adam P. Ganz, Patricia A. Hoverman, J. Russell Langdon, Robert Lyman, Gary H. Meropol, Neal J. Mulvey, Therese Newcomer, Lee Peppercorn, Jeffrey Polite, Blase Raghavan, Derek Rossi, Gregory Saltz, Leonard Schrag, Deborah Smith, Thomas J. Yu, Peter P. Hudis, Clifford A. Schilsky, Richard L. TI American Society of Clinical Oncology Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; HER2-POSITIVE BREAST-CANCER; PLUS ADJUVANT CHEMOTHERAPY; QUALITY-OF-LIFE; TOP 5 LIST; PROSTATE-CANCER; INCREASED SURVIVAL; MULTIPLE-MYELOMA; OPEN-LABEL; CARE C1 [Schnipper, Lowell E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA. [Peppercorn, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mulvey, Therese] Southcoast Ctr Canc Care, Fall River, MA USA. [Davidson, Nancy E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Davidson, Nancy E.] Univ Pittsburgh, Med Ctr, Ctr Canc, Pittsburgh, PA USA. [Dicker, Adam P.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Wollins, Dana S.; Tyne, Courtney; Schilsky, Richard L.] Amer Soc Clin Oncol, Alexandria, VA USA. [Blayney, Douglas W.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Yu, Peter P.] Palo Alto Med Fdn, Palo Alto, CA USA. [Blum, Diane] Natl Executive Serv Corps, New York, NY USA. [Saltz, Leonard; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hoverman, J. Russell] Texas Oncol, Dallas, TX USA. [Langdon, Robert] Nebraska Canc Specialists, Omaha, NE USA. [Lyman, Gary H.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Lyman, Gary H.] Univ Washington, Seattle, WA 98195 USA. [Meropol, Neal J.] Case Western Reserve Univ, Univ Hosp Case Med Ctr Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Newcomer, Lee] UnitedHealthcare, Minneapolis, MN USA. [Polite, Blase] Univ Chicago Med, Chicago, IL USA. [Raghavan, Derek] Levine Canc Inst, Charlotte, NC USA. [Rossi, Gregory] AstraZeneca, Macclesfield, Cheshire, England. [Smith, Thomas J.] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. RP Schnipper, LE (reprint author), 330 Brookline Ave, Boston, MA 02215 USA. EM lschnipp@bidmc.harvard.edu OI Saltz, Leonard/0000-0001-8353-4670 FU NCI NIH HHS [P30 CA008748] NR 56 TC 188 Z9 190 U1 3 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2015 VL 33 IS 23 BP 2563 EP U132 DI 10.1200/JCO.2015.61.6706 PG 27 WC Oncology SC Oncology GA CR9DY UT WOS:000361654600013 PM 26101248 ER PT J AU Achtman, JC Werth, VP AF Achtman, Jordan C. Werth, Victoria P. TI Pathophysiology of cutaneous lupus erythematosus SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID FAMILIAL CHILBLAIN LUPUS; HUMAN KERATINOCYTES; ULTRAVIOLET-LIGHT; SKIN-LESIONS; T-CELLS; APOPTOTIC KERATINOCYTES; EXPRESSION; ALPHA; ASSOCIATION; IRRADIATION AB The pathophysiology of cutaneous lupus erythematosus (CLE) encompasses the complex interactions between genetics, the environment, and cells and their products. Recent data have provided enhanced understanding of these interactions and the mechanism by which they cause disease. A number of candidate genes have been identified which increase the risk of developing CLE. Ultraviolet radiation, the predominant environmental exposure associated with CLE, appears to initiate CLE lesion formation by inducing apoptosis, precipitating autoantigen presentation, and promoting cellular production of specific cytokines. Autoantibodies are a well-known entity in CLE, but their exact role remains unclear. Finally, cells ranging from native skin cells to innate and adaptive immune cells produce cytokines and other molecules and play specific roles in lesion formation and perpetuation. Native skin cells implicated in CLE include keratinocytes and endothelial cells. Innate immune cells crucial to CLE pathophysiology include dendritic cells and neutrophils. The primary adaptive immune cells thought to be involved include Th1 cells, Th17 cells, cytotoxic T cells, and invariant natural killer T cells. Though the pathophysiology of CLE has yet to be fully characterized, current research provides direction for future research and therapies. C1 [Achtman, Jordan C.; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Achtman, Jordan C.; Werth, Victoria P.] Perelman Ctr Adv Med, Dept Dermatol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX This material is supported by the Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. NR 65 TC 8 Z9 8 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PD AUG 10 PY 2015 VL 17 AR 182 DI 10.1186/s13075-015-0706-2 PG 10 WC Rheumatology SC Rheumatology GA CO6QL UT WOS:000359281100001 PM 26257198 ER PT J AU Kwon, MJ Bagonis, M Danuser, G Pellman, D AF Kwon, Mijung Bagonis, Maria Danuser, Gaudenz Pellman, David TI Direct Microtubule-Binding by Myosin-10 Orients Centrosomes toward Retraction Fibers and Subcortical Actin Clouds SO DEVELOPMENTAL CELL LA English DT Article ID SPINDLE ORIENTATION; CARGO RECOGNITION; CORTICAL DYNEIN; CELL-DIVISION; POSITION; FILAMENTS; DYNAMICS; MOTILITY; DOMAIN; MECHANISMS AB Positioning of centrosomes is vital for cell division and development. In metazoan cells, spindle positioning is controlled by a dynamic pool of subcortical actin that organizes in response to the position of retraction fibers. These actin "clouds'' are proposed to generate pulling forces on centrosomes and mediate spindle orientation. However, the motors that pull astral microtubules toward these actin structures are not known. Here, we report that the unconventional myosin, Myo10, couples actin-dependent forces from retraction fibers and subcortical actin clouds to centrosomes. Myo10-mediated centrosome positioning requires its direct microtubule binding. Computational image analysis of large microtubule populations reveals a direct effect of Myo10 on microtubule dynamics and microtubule-cortex interactions. Myo10's role in centrosome positioning is distinct from, but overlaps with, that of dynein. Thus, Myo10 plays a key role in integrating the actin and microtubule cytoskeletons to position centrosomes and mitotic spindles. C1 [Kwon, Mijung; Pellman, David] Dana Farber Canc Inst, Howard Hughes Med Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Kwon, Mijung; Bagonis, Maria; Danuser, Gaudenz; Pellman, David] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Kwon, MJ (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, Dept Pediat Oncol, Boston, MA 02215 USA. EM mijung_kwon@dfci.harvard.edu; david_pellman@dfci.harvard.edu FU Howard Hughes Medical Institute; NIH [GM061345, GM067230]; Leukemia and Lymphoma Society; Susan Komen grant FX We thank M. Thery, B. Akins, H. Arellano-Santoyo, S. Jhaveri-Schneider, and N. Umbreit for comments on the manuscript; L. Ding for sharing computer code; the Nikon Imaging Center at Harvard Medical School and H. Elliott from the Image and Data Analysis Core at Harvard Medical School for their help with kymograph analysis of microtubule dynamics; and R. Cheney, W. Krek, E. Nigg, I. Cheeseman, T. Wittmann, and W. Bement for reagents. D. P. was supported by the Howard Hughes Medical Institute and the NIH (GM061345); M. K. was supported by a special fellow award from the Leukemia and Lymphoma Society and a Susan Komen grant; and M. B. and G. D. were funded by the NIH (GM067230). NR 46 TC 14 Z9 14 U1 2 U2 5 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 AUG 10 PY 2015 VL 34 IS 3 BP 323 EP 337 DI 10.1016/j.devcel.2015.06.013 PG 15 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CO9KY UT WOS:000359495900007 PM 26235048 ER PT J AU Papas, KK Bellin, MD Sutherland, DER Suszynski, TM Kitzmann, JP Avgoustiniatos, ES Gruessner, AC Mueller, KR Beilman, GJ Balamurugan, AN Loganathan, G Colton, CK Koulmanda, M Weir, GC Wilhelm, JJ Qian, DJ Niland, JC Hering, BJ AF Papas, Klearchos K. Bellin, Melena D. Sutherland, David E. R. Suszynski, Thomas M. Kitzmann, Jennifer P. Avgoustiniatos, Efstathios S. Gruessner, Angelika C. Mueller, Kathryn R. Beilman, Gregory J. Balamurugan, Appakalai N. Loganathan, Gopalakrishnan Colton, Clark K. Koulmanda, Maria Weir, Gordon C. Wilhelm, Josh J. Qian, Dajun Niland, Joyce C. Hering, Bernhard J. TI Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation SO PLOS ONE LA English DT Article ID BETA-CELL MASS; TOTAL PANCREATECTOMY; IMMUNOSUPPRESSIVE REGIMEN; CHRONIC-PANCREATITIS; DIABETES-MELLITUS; TRANSPLANTATION; OUTCOMES; REVERSAL AB Background Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity. Methods Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis. Results Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6-12 months post-IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72). Conclusions Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations. C1 [Papas, Klearchos K.; Kitzmann, Jennifer P.; Gruessner, Angelika C.; Mueller, Kathryn R.] Univ Arizona, Dept Surg, Inst Cellular Transplantat, Tucson, AZ 85721 USA. [Papas, Klearchos K.; Bellin, Melena D.; Sutherland, David E. R.; Suszynski, Thomas M.; Kitzmann, Jennifer P.; Avgoustiniatos, Efstathios S.; Mueller, Kathryn R.; Beilman, Gregory J.; Balamurugan, Appakalai N.; Loganathan, Gopalakrishnan; Wilhelm, Josh J.; Hering, Bernhard J.] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. [Papas, Klearchos K.; Bellin, Melena D.; Sutherland, David E. R.; Suszynski, Thomas M.; Kitzmann, Jennifer P.; Avgoustiniatos, Efstathios S.; Mueller, Kathryn R.; Balamurugan, Appakalai N.; Loganathan, Gopalakrishnan; Wilhelm, Josh J.; Hering, Bernhard J.] Schulze Diabet Inst, Minneapolis, MN USA. [Colton, Clark K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Koulmanda, Maria] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplant Inst, Boston, MA 02215 USA. [Weir, Gordon C.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Qian, Dajun; Niland, Joyce C.] City Hope Natl Med Ctr, Informat Sci, Duarte, CA USA. RP Papas, KK (reprint author), Univ Arizona, Dept Surg, Inst Cellular Transplantat, Tucson, AZ 85721 USA. EM kkpapas@surgery.arizona.edu OI Beilman, Gregory/0000-0001-5036-3027 FU NIH; Carol Olson Memorial Diabetes Research Fund; Schott Foundation; Iacocca Foundation; NIDDK [K23 DK084315] FX This work was supported in part by the NIH (Clinical Islet Transplantation [CIT] Consortium grant, Iscel Cell Resources [ICR] grant), by the Carol Olson Memorial Diabetes Research Fund, Schott Foundation, Iacocca Foundation, and NIDDK #K23 DK084315. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 8 Z9 8 U1 2 U2 9 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 AUG 10 PY 2015 VL 10 IS 8 AR e0134428 DI 10.1371/journal.pone.0134428 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO7PJ UT WOS:000359352600014 PM 26258815 ER PT J AU Mundon, CR Anderson, ML Najavits, LM AF Mundon, Chandra R. Anderson, Melissa L. Najavits, Lisa M. TI Attitudes toward Substance Abuse Clients: An Empirical Study of Clinical Psychology Trainees SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE clinical psychology training; stigma; substance abuse; substance use disorder ID MENTAL-ILLNESS; DOCTORAL PROGRAMS; SOCIAL DISTANCE; DRUG PROBLEMS; USE DISORDER; ALCOHOL; ADDICTION; RESPONSIBILITY; SCHIZOPHRENIA; DANGEROUSNESS AB Despite the high prevalence of substance use disorder (SUD) and its frequent comorbidity with mental illness, individuals with SUD are less likely to receive effective SUD treatment from mental health practitioners than SUD counselors. Limited competence and interest in treating this clinical population are likely influenced by a lack of formal training in SUD treatment. Using a factorial survey-vignette design that included three clinical vignettes and a supplementary survey instrument, we investigated whether clinical psychology doctoral students differ in their level of negative emotional reactions toward clients with SUD versus major depressive disorder (MDD); whether they differ in their attributions for SUD versus MDD; and how their negative emotional reactions and attributions impact their interest in pursuing SUD clinical work. Participants were 155 clinical psychology graduate-level doctoral students (72% female). Participants endorsed more negative emotional reactions toward clients with SUD than toward clients with MDD. They were also more likely to identify poor willpower as the cause for SUD than for MDD. More than a third reported interest in working with SUD populations. Highest levels of interest were associated with prior professional and personal experience with SUD, four to six years of clinical experience, and postmodern theoretical orientation. C1 [Mundon, Chandra R.] Univ Oregon, Ctr Counseling, Eugene, OR 97403 USA. [Anderson, Melissa L.] Univ Massachusetts, Sch Med, Psychiat, Worcester, MA 01655 USA. [Najavits, Lisa M.] VA Boston Healthcare Syst, Boston, MA USA. [Najavits, Lisa M.] Boston Univ, Sch Med, Psychiat, Boston, MA 02118 USA. RP Anderson, ML (reprint author), Univ Massachusetts, Sch Med, Dept Psychiat, 55 Lake Ave North, Worcester, MA 01655 USA. EM melissa.anderson@umassmed.edu FU NCATS NIH HHS [KL2 TR000160, KL2 TR001455] NR 32 TC 0 Z9 0 U1 2 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0279-1072 EI 2159-9777 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD AUG 8 PY 2015 VL 47 IS 4 BP 293 EP 300 DI 10.1080/02791072.2015.1076090 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA CT3RT UT WOS:000362725300005 PM 26375324 ER PT J AU Riesel, JN Mandigo, M Gillies, R Damuse, R Farmer, PE Cusack, JC Krakauer, EL Shulman, LN AF Riesel, Johanna N. Mandigo, Morgan Gillies, Rowan Damuse, Ruth Farmer, Paul E. Cusack, James C. Krakauer, Eric L. Shulman, Lawrence N. TI Surgical palliative care in resource-limited settings SO LANCET LA English DT Letter C1 [Riesel, Johanna N.; Mandigo, Morgan; Gillies, Rowan] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA 02114 USA. [Farmer, Paul E.; Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Cusack, James C.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Krakauer, Eric L.; Shulman, Lawrence N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Riesel, Johanna N.; Mandigo, Morgan; Gillies, Rowan] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. [Riesel, Johanna N.; Cusack, James C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Krakauer, Eric L.] Massachusetts Gen Hosp, Div Palliat Care, Boston, MA 02114 USA. [Mandigo, Morgan] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Damuse, Ruth] Zanmi Lasante Partners Hlth, Mirebalais, Haiti. [Farmer, Paul E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Shulman, Lawrence N.] Dana Farber Canc Inst, Dept Haematol & Oncol, Boston, MA 02115 USA. RP Riesel, JN (reprint author), Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA 02114 USA. EM jriesel@mgh.harvard.edu NR 6 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 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD AUG 8 PY 2015 VL 386 IS 9993 BP 527 EP 527 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CO8PG UT WOS:000359431900015 PM 25924837 ER PT J AU Meara, JG Leather, AJM Hagander, L Alkire, BC Alonso, N Ameh, EA Bickler, SW Conteh, L Dare, AJ Davies, J Merisier, ED El-Halabi, S Farmer, PE Gawande, A Gillies, R Greenberg, SLM Grimes, CE Gruen, RL Ismail, EA Kamara, TB Lavy, C Lundeg, G Mkandawire, NC Raykar, NP Riesel, JN Rodas, E Rose, J Roy, N Shrime, MG Sullivan, R Verguet, S Watters, D Weiser, TG Wilson, IH Yamey, G Yip, W AF Meara, John G. Leather, Andrew J. M. Hagander, Lars Alkire, Blake C. Alonso, Nivaldo Ameh, Emmanuel A. Bickler, Stephen W. Conteh, Lesong Dare, Anna J. Davies, Justine Merisier, Eunice Derivois El-Halabi, Shenaaz Farmer, Paul E. Gawande, Atul Gillies, Rowan Greenberg, Sarah L. M. Grimes, Caris E. Gruen, Russell L. Ismail, Edna Adan Kamara, Thaim Buya Lavy, Chris Lundeg, Ganbold Mkandawire, Nyengo C. Raykar, Nakul P. Riesel, Johanna N. Rodas, Edgar Rose, John Roy, Nobhojit Shrime, Mark G. Sullivan, Richard Verguet, Stephane Watters, David Weiser, Thomas G. Wilson, Iain H. Yamey, Gavin Yip, Winnie TI Global Surgery 2030: evidence and solutions for achieving health, welfare, and economic development SO LANCET LA English DT Review ID MIDDLE-INCOME-COUNTRIES; EMERGENCY OBSTETRIC CARE; CONTINUING MEDICAL-EDUCATION; POST-2015 DEVELOPMENT AGENDA; SURGICAL SAFETY CHECKLIST; ESSENTIAL-TRAUMA-CARE; SUB-SAHARAN AFRICA; QUALITY-OF-CARE; SIERRA-LEONE; OPERATIONS MANAGEMENT C1 [Meara, John G.; Greenberg, Sarah L. M.; Raykar, Nakul P.; Riesel, Johanna N.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA 02115 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Meara, John G.; Greenberg, Sarah L. M.; Raykar, Nakul P.; Riesel, Johanna N.] Boston Childrens Hosp, Boston, MA USA. [Leather, Andrew J. M.; Dare, Anna J.; Grimes, Caris E.] Kings Hlth Partners, Kings Ctr Global Hlth, London, England. [Leather, Andrew J. M.; Dare, Anna J.; Grimes, Caris E.] Kings Coll London, London WC2R 2LS, England. [Hagander, Lars] Lund Univ, Dept Pediat, Clin Sci Lund, Pediat Surg & Global Pediat, Lund, Sweden. [Alkire, Blake C.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Alonso, Nivaldo] Univ Sao Paulo, Dept Plast Surg, Sao Paulo, Brazil. [Ameh, Emmanuel A.] Natl Hosp, Div Peadiatr Surg, Dept Surg, Abuja, Nigeria. [Bickler, Stephen W.] Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA 92103 USA. [Rose, John] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. [Conteh, Lesong] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. [Davies, Justine] The Lancet, London NW1 7BY, England. [Merisier, Eunice Derivois] Dept Minist Hlth, Gressier, Ouest, Haiti. [Farmer, Paul E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Div Global Hlth Equ, Boston, MA 02115 USA. [Farmer, Paul E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Farmer, Paul E.] Partners Hlth, Boston, MA USA. [Gawande, Atul; Rose, John] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Gawande, Atul] Ariadne Labs Boston, Boston, MA USA. [Gillies, Rowan] Royal N Shore Hosp, St Leonards, NSW 2065, Australia. [Greenberg, Sarah L. M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gruen, Russell L.] Alfred Hosp, Melbourne, Vic, Australia. [Gruen, Russell L.] Monash Univ, Melbourne, Vic 3004, Australia. [Gruen, Russell L.] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore. [Ismail, Edna Adan] Edna Adan Univ Hosp, Hargeisa, Somalia. [Kamara, Thaim Buya] Connaught Hosp, Freetown, Sierra Leone. [Kamara, Thaim Buya] Univ Sierra Leone, Dept Surg, Freetown, Sierra Leone. [Lavy, Chris] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England. [Lundeg, Ganbold] Mongolian Natl Univ Med Sci, Ulaanbaatar, Mongol Peo Rep. [Mkandawire, Nyengo C.] Univ Malawi, Coll Med, Dept Surg, Blantyre, Malawi. [Mkandawire, Nyengo C.] Flinders Univ S Australia, Sch Med, Adelaide, SA 5001, Australia. [Raykar, Nakul P.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Riesel, Johanna N.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rodas, Edgar] Univ Cuenca, Cinterandes Fdn, Cuenca, Ecuador. [Rodas, Edgar] Univ Azuay, Cuenca, Ecuador. [Roy, Nobhojit] Govt India, BARC Hosp, Bombay, Maharashtra, India. [Shrime, Mark G.] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. [Sullivan, Richard] Kings Coll London, Inst Canc Policy, Kings Hlth Partners Integrated Canc Ctr, Kings Ctr Global Hlth, London WC2R 2LS, England. [Verguet, Stephane] Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Watters, David] Royal Australasian Coll Surg, East Melbourne, Vic, Australia. [Watters, David] Deakin Univ, Melbourne, Vic, Australia. [Weiser, Thomas G.] Stanford Univ, Dept Surg, Sch Med, Stanford, CA 94305 USA. [Wilson, Iain H.] Royal Devon & Exeter NHS Fdn Trust, Dept Anaesthesia, Exeter, Devon, England. [Yamey, Gavin] Univ Calif San Francisco, Evidence Policy Initiat, Global Hlth Grp, San Francisco, CA 94143 USA. [Yip, Winnie] Univ Oxford, Blavatnik Sch Govt, Oxford, England. RP Meara, JG (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA 02115 USA. EM john.meara@childrens.harvard.edu OI Sullivan, Richard/0000-0002-6435-1825 FU Association of Anaesthetists of Great Britain and Ireland; Babson College; Bill & Melinda Gates Foundation; Boston Children's Hospital; Dubai Harvard Foundation for Medical Research; FAPESP Fundacao de Amparo a Pesquisa de Sao Paolo; Harvard Business School; Harvard Medical School Center for Global Health Delivery-Dubai; Harvard Medical School Department of Global Health and Social Medicine; Indian Institute of Management Bangalore; King's College London; Lund University; Melbourne Business School; National Cancer Institute; Operation Smile; Pershing Square; Steven C. and Carmella R. Kletjian Foundation, Inc.; Royal College of Surgeons in Ireland; Royal College of Surgeons of Edinburgh; Rockefeller Foundation; University of Virgina Darden School of Business FX We dedicate this report to Edgar Rodas, who was a commissioner, colleague, and friend. Edgar sadly died on March 2, 2015. The work in this report was enhanced by the generous financial or in-kind support that we received from the following organisations: Association of Anaesthetists of Great Britain and Ireland, Babson College, Bill & Melinda Gates Foundation, Boston Children's Hospital, Dubai Harvard Foundation for Medical Research, FAPESP Fundacao de Amparo a Pesquisa de Sao Paolo, Harvard Business School, Harvard Medical School Center for Global Health Delivery-Dubai, Harvard Medical School Department of Global Health and Social Medicine, Indian Institute of Management Bangalore, King's College London, Lund University, Melbourne Business School, National Cancer Institute, Operation Smile, Pershing Square, Steven C. and Carmella R. Kletjian Foundation, Inc., Royal College of Surgeons in Ireland, The Royal College of Surgeons of Edinburgh, The Rockefeller Foundation, and University of Virgina Darden School of Business. We are grateful to the hundreds of people who contributed to this report. Contributors are listed in the appendix. NR 321 TC 148 Z9 151 U1 14 U2 42 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD AUG 8 PY 2015 VL 386 IS 9993 BP 569 EP 624 DI 10.1016/S0140-6736(15)60160-X PG 56 WC Medicine, General & Internal SC General & Internal Medicine GA CO8PG UT WOS:000359431900031 PM 25924834 ER PT J AU Hsu, JJ AF Hsu, Jung-Jiin TI Flip-angle profile of slice-selective excitation and the measurement of the MR longitudinal relaxation time with steady-state magnetization SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE flip angle profile; longitudinal relaxation time; T-1 measurement; steady-state magnetization; slice profile; DESPOT ID RF PULSE-SHAPE; RADIOFREQUENCY FIELD; SPOILED FLASH; T-1; RESONANCE; ACCURATE; T1; T2; ACQUISITION; NMR AB In MRI, the flip angle (FA) of slice-selective excitation is not uniform across the slice-thickness dimension. This work investigates the effect of the non-uniform FA profile on the accuracy of a commonly-used method for the measurement, in which the T-1 value, i.e., the longitudinal relaxation time, is determined from the steady-state signals of an equally-spaced RF pulse train. By using the numerical solutions of the Bloch equation, it is shown that, because of the non-uniform FA profile, the outcome of the T-1 measurement depends significantly on T-1 of the specimen and on the FA and the inter-pulse spacing tau of the pulse train. A new method to restore the accuracy of the T-1 measurement is described. Different from the existing approaches, the new method also removes the FA profile effect for the measurement of the FA, which is normally a part of the T-1 measurement. In addition, the new method does not involve theoretical modeling, approximation, or modification to the underlying principle of the T-1 measurement. An imaging experiment is performed, which shows that the new method can remove the FA-, the tau-, and the T-1-dependence and produce T-1 measurements in excellent agreement with the ones obtained from a gold standard method (the inversion-recovery method). C1 [Hsu, Jung-Jiin] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Hsu, Jung-Jiin] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94121 USA. RP Hsu, JJ (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, 4150 Clement St Bldg 13 114M, San Francisco, CA 94121 USA. EM jj.jason.hsu@outlook.com FU US Department of Defense [W81XWH-10-2-0078] FX This work is supported in part by a grant from the US Department of Defense (W81XWH-10-2-0078; PI: Michael Weiner). The Author thanks Gerald Matson and Norbert Schuff for helpful discussion during manuscript preparation. NR 25 TC 0 Z9 0 U1 1 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 AUG 7 PY 2015 VL 60 IS 15 BP 5785 EP 5801 DI 10.1088/0031-9155/60/15/5785 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CR0VH UT WOS:000361040900006 PM 26159799 ER PT J AU Goertz, L Tsiamas, P Karellas, A Sajo, E Zygmanski, P AF Goertz, Lukas Tsiamas, Panagiotis Karellas, Andrew Sajo, Erno Zygmanski, Piotr TI Monte Carlo simulation of a prototypical patient dosimetry system for fluoroscopic procedures SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE real-time dosimetry; fluoroscopy; thin-film detector arrays; Monte Carlo; peak skin dose; entrance dose; integral dose ID GUIDED PROCEDURES; RADIOCHROMIC FILM; SKIN INJURIES; RADIATION; INTERVENTIONS; DETECTOR; QUALITY AB The purpose of this study is to investigate feasibility of a novel real-time dosimetry method for fluoroscopically guided interventions utilizing thin-film detector arrays in several potential locations with respect to the patient and x-ray equipment. We employed Monte Carlo (MC) simulation to establish the fluoroscopic beam model to determine dosimetric quantities directly from measured doses in thin-film detector arrays at three positions: A-attached to the x-ray source, B-on the couch under the patient and C-attached to the fluoroscopic imager. Next, we developed a calibration method to determine skin dose at the entry of the beam (Dentr) as well as the dose distribution along each ray of the beam in a water-equivalent patient model. We utilized the concept of water-equivalent thickness to determine the dose inside the patient based on doses measured outside of the patient by the thin-film detector array layers: (a) A, (b) B, or (c) B and C. In the process of calibration we determined a correction factor that characterizes the material-specific response of the detector, backscatter factor and attenuation factor for slab water phantoms of various thicknesses. Application of this method to an anthropomorphic phantom showed accuracy of about 1% for Dentr and up to about 10% for integral dose along the beam path when compared to a direct simulation of dose by MC. C1 [Goertz, Lukas; Tsiamas, Panagiotis; Zygmanski, Piotr] Dana Farber Canc Inst, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Goertz, Lukas; Tsiamas, Panagiotis; Zygmanski, Piotr] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Goertz, Lukas; Sajo, Erno] Univ Massachusetts, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA 01854 USA. [Goertz, Lukas] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Radiat Oncol, D-69115 Heidelberg, Germany. [Karellas, Andrew] Univ Massachusetts, Dept Radiol, Sch Med, Worcester, MA 01655 USA. RP Goertz, L (reprint author), Dana Farber Canc Inst, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. EM lukas.goertz@medma.uni-heidelberg.de; pzygmanski@lroc.harvard.edu NR 31 TC 2 Z9 2 U1 0 U2 0 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 AUG 7 PY 2015 VL 60 IS 15 BP 5891 EP 5909 DI 10.1088/0031-9155/60/15/5891 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CR0VH UT WOS:000361040900012 PM 26184743 ER PT J AU Gholami, Y Zhu, X Fulton, R Meikle, S El-Fakhri, G Kuncic, Z AF Gholami, Y. Zhu, X. Fulton, R. Meikle, S. El-Fakhri, G. Kuncic, Z. TI Stochastic simulation of radium-223 dichloride therapy at the sub-cellular level SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE radionuclide therapy; Monte Carlo modelling; radium-223 dichloride ID PROSTATE-CANCER; BONE METASTASES; ALPHA-PARTICLES; SURVIVAL; TOOLKIT AB Radium-223 dichloride (Ra-223) is an alpha particle emitter and a natural boneseeking radionuclide that is currently used for treating osteoblastic bone metastases associated with prostate cancer. The stochastic nature of alpha emission, hits and energy deposition poses some challenges for estimating radiation damage. In this paper we investigate the distribution of hits to cells by multiple alpha particles corresponding to a typical clinically delivered dose using a Monte Carlo model to simulate the stochastic effects. The number of hits and dose deposition were recorded in the cytoplasm and nucleus of each cell. Alpha particle tracks were also visualized. We found that the stochastic variation in dose deposited in cell nuclei (similar or equal to 40%) can be attributed in part to the variation in LET with pathlength. We also found that similar or equal to 18% of cell nuclei receive less than one sigma below the average dose per cell (similar or equal to 15.4 Gy). One possible implication of this is that the efficacy of cell kill in alpha particle therapy need not rely solely on ionization clustering on DNA but possibly also on indirect DNA damage through the production of free radicals and ensuing intracellular signaling. C1 [Gholami, Y.; Fulton, R.; Meikle, S.] Univ Sydney, Fac Res Grp, Brain & Mind Res Inst Med Imaging & Radiat Sci, Sydney, NSW 2006, Australia. [Zhu, X.; El-Fakhri, G.] Harvard Univ, Sch Med, Ctr Adv Radiol Sci, Cambridge, MA 02138 USA. [Zhu, X.; El-Fakhri, G.] Massachusetts Gen Hosp, Div Nucl Med & MolecularImaging, Radiol, Boston, MA 02114 USA. [Gholami, Y.; Fulton, R.; Kuncic, Z.] Univ Sydney, Sch Phys, Sydney, NSW 2006, Australia. RP Gholami, Y (reprint author), Univ Sydney, Fac Res Grp, Brain & Mind Res Inst Med Imaging & Radiat Sci, Sydney, NSW 2006, Australia. EM zdenka.kuncic@sydney.edu.au OI Fulton, Roger/0000-0003-2536-2190 NR 23 TC 1 Z9 1 U1 1 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 7 PY 2015 VL 60 IS 15 BP 6087 EP 6096 DI 10.1088/0031-9155/60/15/6087 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CR0VH UT WOS:000361040900022 PM 26216391 ER PT J AU Steffel, J Robertson, M Singh, JP Abraham, WT Bax, JJ Borer, JS Dickstein, K Ford, I Gorcsan, J Gras, D Krum, H Sogaard, P Holzmeister, J Brugada, J Ruschitzka, F AF Steffel, Jan Robertson, Michele Singh, Jagmeet P. Abraham, William T. Bax, Jeroen J. Borer, Jeffrey S. Dickstein, Kenneth Ford, Ian Gorcsan, John, III Gras, Daniel Krum, Henry Sogaard, Peter Holzmeister, Johannes Brugada, Josep Ruschitzka, Frank TI The effect of QRS duration on cardiac resynchronization therapy in patients with a narrow QRS complex: a subgroup analysis of the EchoCRT trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Cardiac resynchronization therapy; Narrow QRS; QRS duration ID CHRONIC HEART-FAILURE; DYSSYNCHRONY; MORBIDITY; MORTALITY AB Aims In EchoCRT, a randomized trial evaluating the effect of cardiac resynchronization therapy (CRT) in patients with a QRS duration of <130 ms and echocardiographic evidence of left ventricular dyssynchrony, the primary outcome occurred more frequently in the CRT when compared with the control group. According to current heart failure guidelines, CRT is recommended in patients with a QRS duration of >= 120 ms. However, there is some ambiguity from clinical trial data regarding the benefit of patients with a QRS duration of 120-130 ms. Methods and results The main EchoCRT trial was prematurely terminated due to futility. For the current subgroup analysis we compared data for CRT-ON vs. -OFF in patients with QRS < 120 (n = 661) and QRS 120-130 ms (n = 139). On uni- and multivariable analyses, no significant interaction was observed between the two groups and randomized treatment for the primary or any of the secondary endpoints. On multivariable analysis, a higher risk for the primary endpoint was observed in patients with a QRS duration of 120-130 ms randomized to CRT-ON vs. CRT-OFF (hazard ratio 2.18, 95% CI 1.02-4.65; P = 0.044). However, no statistically significant interaction, compared with patients with QRS < 120 ms randomized to CRT-ON vs. CRT-OFF, was noted (P-interaction = 0.160). Conclusions In this pre-specified subgroup analysis of EchoCRT, no benefit of CRT was evident in patients with a QRS duration of 120-130 ms. These data further question the usefulness of CRT in this patient population. C1 [Steffel, Jan; Holzmeister, Johannes; Ruschitzka, Frank] Univ Heart Ctr Zurich, Dept Cardiol, Heart Failure Clin & Transplantat, Zurich, Switzerland. [Robertson, Michele; Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. [Abraham, William T.] Ohio State Univ, Med Ctr, Davis Heart & Lung Res Inst, Div Cardiovasc Med, Columbus, OH 43210 USA. [Bax, Jeroen J.] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Borer, Jeffrey S.] State Univ New York Downstate Coll Med, Div Cardiovasc Med, New York, NY USA. [Borer, Jeffrey S.] State Univ New York Downstate Coll Med, Howard Gilmanand Ron Inst, New York, NY USA. [Borer, Jeffrey S.] State Univ New York Downstate Coll Med, Jean Schiavone Inst, New York, NY USA. [Dickstein, Kenneth] Univ Bergen, Stavanger Univ Hosp, Stavanger, Norway. [Gorcsan, John, III] Univ Pittsburgh, Pittsburgh, PA USA. [Gras, Daniel] Nouvelles Clin Nantaises, Nantes, France. [Krum, Henry] Monash Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic, Australia. [Sogaard, Peter] Aalborg Univ, Aalborg, Denmark. [Brugada, Josep] Univ Barcelona, Hosp Clin, Thorax Inst, Cardiol Dept, E-08007 Barcelona, Spain. RP Ruschitzka, F (reprint author), Univ Heart Ctr Zurich, Dept Cardiol, Heart Failure Clin & Transplantat, Zurich, Switzerland. EM frank.ruschitzka@googlemail.com FU Amgen; Astra-Zeneca; Bayer; Biotronik; Biosense Webster; Boehringer-Ingelheim; Boston Scientific; Bristol-Myers Squibb; Daiichi-Sankyo; Cook Medical; Medtronic; Novartis; Pfizer; Roche; Sanofi-Aventis; Sorin; St. Jude Medical; Bayer Healthcare; Sorin Group; CardioInsight; Respicardia Inc.; GE Healthcare; Lantheus; Servier; Edwards Lifesciences; Cardiorentis; ARMGO; Celladon; RESMED; GE; EBR systems FX J.S. reports consultant and/or speaker fees from Amgen, Astra-Zeneca, Bayer, Biotronik, Biosense Webster, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi-Sankyo, Cook Medical, Medtronic, Novartis, Pfizer, Roche, Sanofi-Aventis, Sorin, and St. Jude Medical and is co-director of CorXL. He reports grant support through his institution from Bayer Healthcare, Biotronik, Daiichi-Sankyo, Medtronic, and St. Jude Medical. J.P.S. reports grants and personal fees from Biotronik, grants and personal fees from Boston Scientific, grants and personal fees from Medtronic, grants from St. Jude Medical, personal fees from Sorin Group, personal fees from CardioInsight, personal fees from Respicardia Inc. during the conduct of the study. W.T.A. reports grant support and personal fees from Biotronik during the conduct of the study; and grant support and personal fees from Medtronic and St. Jude Medical outside the submitted work. J.J.B. reports grant support from GE Healthcare, Biotronik, Boston Scientific, Medtronic, Lantheus, Servier, and Edwards Lifesciences outside the submitted work. J.S.B. reports personal fees from Biotronik during the conduct of the study; and personal fees from Servier, Cardiorentis, ARMGO, Novartis, and Celladon outside the submitted work. K.D. reports personal fees from Biotronik during the conduct of the study; and personal fees from Medtronic, Sorin, and Boston Scientific outside the submitted work. I.F. reports grant support from Biotronik during the conduct of the study; grant support and personal fees from Servier, and Medtronic, and personal fees from RESMED outside the submitted work. J.G. has received research grant support from Biotronik, Medtronic, and GE. D.G. reports personal fees from Medtronic, St. Jude Medical, Boston Scientific, and Biotronik outside the submitted work. H.K. reports personal fees from Biotronik outside the submitted work. P.S. has received consultant fees from Biotronik, speaker fees from GE HealthCare, and research grants from Biotronik, GE Health Care, Bayer, and EBR systems. J.H. reports grant support from St. Jude Medical and grant support and personal fees from Biotronik during the conduct of the study; and other support from Cardiorentis outside the submitted work. J.B. has nothing to disclose. F.R. reports personal fees from Biotronik during the conduct of the study; and personal fees from Servier, Cardiorentis, and St. Jude Medical outside the submitted work. NR 23 TC 11 Z9 11 U1 2 U2 3 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 AUG 7 PY 2015 VL 36 IS 30 BP 1983 EP 1989 DI 10.1093/eurheartj/ehv242 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP1XE UT WOS:000359670100015 PM 26009595 ER PT J AU Artinian, N Cloninger, C Holmes, B Benavides-Serrato, A Bashir, T Gera, J AF Artinian, Nicholas Cloninger, Cheri Holmes, Brent Benavides-Serrato, Angelica Bashir, Tariq Gera, Joseph TI Phosphorylation of the Hippo Pathway Component AMOTL2 by the mTORC2 Kinase Promotes YAP Signaling, Resulting in Enhanced Glioblastoma Growth and Invasiveness SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YES-ASSOCIATED PROTEIN-1; TUMOR-SUPPRESSOR; MOLECULAR PATHOLOGY; COMPLEX; GLIOMAS; ONCOPROTEIN; INHIBITION; RESISTANCE; REGULATOR; CANCER AB The mechanistic target of rapamycin (mTOR) and Hippo signaling pathways are two major signaling cascades that coordinately regulate cell growth and proliferation. Dysregulation of these pathways plays a critical role in gliomagenesis. Recent reports have provided evidence of cross-talk between the mTOR and Hippo pathways; however, a complete description of the signaling relationships between these pathways remains to be elucidated. Utilizing a gene-trapping strategy in a mouse glioma model, we report the identification of AMOTL2 as a candidate substrate for mTORC2. AMOTL2 is phosphorylated at serine 760 by mTORC2. Mutation of AMOTL2 mimicking constitutive Ser(760) phosphorylation blocks its ability to bind and repress YAP leading to increased relative expression of known YAP gene targets. Moreover, overexpression of AMOTL2 or a non-phosphorylatable AMOTL2-S760A mutant inhibited YAP-induced transcription, foci formation, growth, and metastatic properties, whereas overexpression of a phosphomimetic AMOTL2-S760E mutant negated these repressive effects of AMOTL2 in glioblastoma (GBM) cells in vitro. Similar effects on xenograft growth were observed in GBM cells expressing these AMOTL2 Ser(760) mutants. YAP was also shown to be required for Rictor-mediated GBM growth and survival. Finally, an analysis of mTORC2/AMOTL2/YAP activities in primary GBM samples supported the clinical relevance of this signaling cascade, and we propose that pharmacological agents cotargeting these regulatory circuits may hold therapeutic potential. C1 [Artinian, Nicholas; Bashir, Tariq; Gera, Joseph] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Gera, Joseph] Univ Calif Los Angeles, Jonnson Comprehens Canc Ctr, Los Angeles, CA 90048 USA. [Gera, Joseph] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90048 USA. [Artinian, Nicholas; Cloninger, Cheri; Holmes, Brent; Benavides-Serrato, Angelica; Bashir, Tariq; Gera, Joseph] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Res & Dev, Los Angeles, CA 91343 USA. RP Gera, J (reprint author), 16111 Plummer St 151 Bldg 1,Rm C111A, Los Angeles, CA 91343 USA. EM jgera@mednet.ucla.edu RI Regan, Clinton/E-6250-2012 FU National Institutes of Health [R01CA168700]; Department of Veterans Affairs FX This work was supported, in whole or in part, by National Institutes of Health Grant R01CA168700. This work was also supported by the Department of Veterans Affairs. The authors declare that they have no conflicts of interest with the contents of this article. NR 46 TC 6 Z9 6 U1 0 U2 10 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 AUG 7 PY 2015 VL 290 IS 32 BP 19387 EP 19401 DI 10.1074/jbc.M115.656587 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CO7TL UT WOS:000359364600001 PM 25998128 ER PT J AU Huang, J Wang, L Cong, ZY Amoozgar, Z Kiner, E Xing, DY Orsulic, S Matulonis, U Goldberg, MS AF Huang, Jing Wang, Lei Cong, Zhongyi Amoozgar, Zohreh Kiner, Evgeny Xing, Deyin Orsulic, Sandra Matulonis, Ursula Goldberg, Michael S. TI The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(-/-) murine model of ovarian cancer SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE BMN 673; PARP1; Ovarian cancer; Immune microenvironment ID TUMOR-INFILTRATING LYMPHOCYTES; CELL LUNG-CANCER; PROGNOSTIC-SIGNIFICANCE; INTERFERON-GAMMA; MOUSE MODEL; DNA-REPAIR; CARCINOMA; OLAPARIB; THERAPY; GROWTH AB Familial breast and ovarian cancer are often caused by inherited mutations of BRCAL While current prognoses for such patients are rather poor, inhibition of poly-ADP ribose polymerase 1 (PARPI) induces synthetic lethality in cells that are defective in homologous recombination. BMN 673 is a potent PARP1 inhibitor that is being clinically evaluated for treatment of BRCA-mutant cancers. Using the Brca1-deficient murine epithelial ovarian cancer cell line BR5FVB1-Akt, we investigated whether the antitumor effects of BMN 673 extend beyond its known pro-apoptotic function. Administration of modest amounts of BMN 673 greatly improved the survival of mice bearing subcutaneous or intraperitoneal tumors. We thus hypothesized that BMN 673 may influence the composition and function of immune cells in the tumor microenvironment. Indeed, BMN 673 significantly increases the number of peritoneal CD8(+) T cells and NK cells as well as their production of IFN-gamma and TNF-alpha. These data suggest that the cell stress caused by BMN 673 induces not only cancer cell-intrinsic apoptosis but also cancer cell-extrinsic antitumor immune effects in a syngeneic murine model of ovarian cancer. BMN 673 may therefore serve as a promising adjuvant therapy to immunotherapy to achieve durable responses among patients whose tumors harbor defects in homologous recombination. (C) 2015 Elsevier Inc. All rights reserved. C1 [Huang, Jing; Wang, Lei; Cong, Zhongyi; Amoozgar, Zohreh; Kiner, Evgeny; Goldberg, Michael S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Huang, Jing] Peking Univ, Sch Basic Med Sci, Dept Immunol, Beijing 100871, Peoples R China. [Cong, Zhongyi] Jilin Univ, Sch Pharmaceut Sci, Dept Regenerat Med, Changchun 130023, Peoples R China. [Amoozgar, Zohreh] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Xing, Deyin] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Orsulic, Sandra] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Matulonis, Ursula] Dana Farber Canc Inst, Gynecol Oncol Program, Boston, MA 02115 USA. RP Goldberg, MS (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM michael_goldberg1@dfci.harvard.edu FU China Scholarship Council; Susan Smith Center for Women's Cancer FX We thank the China Scholarship Council for its financial support of Dr. Jing Huang and Dr. Zhongyi Cong as well as the Susan Smith Center for Women's Cancer for its support of this work. NR 24 TC 6 Z9 6 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 7 PY 2015 VL 463 IS 4 BP 551 EP 556 DI 10.1016/j.bbrc.2015.05.083 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CN5FN UT WOS:000358455300013 PM 26047697 ER PT J AU Lee, C Jones, A Kainz, D Khan, F Carrithers, MD AF Lee, Cara Jones, Alexis Kainz, Danielle Khan, Faatima Carrithers, Michael D. TI A sodium channel variant in Aedes aegypti as a candidate pathogen sensor for viral-associated molecular patterns SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Para; Yellow fever mosquito; Imidazolquinilone; RelA; ssRNA ID NAV1.5; SEQUENCE AB Recent work demonstrated that a splice variant of a human macrophage voltage-gated sodium channel expressed on endosomes acts as an intracellular sensor for dsRNA, a viral-associated molecular pattern. Here our goal was to identify a candidate gene in a clinically relevant invertebrate model with related cellular and pattern recognition properties. The para gene in drosophila and other insects encodes voltage-gated sodium channels with similar electrophysiological properties to those found in vertebrate excitable membranes. A database search revealed that the AAEL006019 gene in Aedes aegypti, the yellow fever mosquito, encodes a voltage-gated sodium channel that is distinct from genes that encode para-like sodium channels. As compared to para-like channels, the protein products from this gene have deletions in the N-terminus and in the DII-DIII linker region. When over-expressed in an Aedes aegypti cell line, CCL-125, the AAEL006019 channel demonstrated cytoplasmic expression on vesicular-like organelles. Electrophysiologic analysis revealed that the channel mediates small inward currents that are enhanced by synthetic mimics of viral-derived ssRNA, R848 and ORNO2, but not the dsRNA mimic, poly I:C. R848 treatment of CCL-125 cells that express high levels of the channels led to increased expression of RelA and Ago2, two mediators of insect innate immunity. These results suggest that the AAEL006019 channel acts as an intracellular pathogen sensor for ssRNA molecular patterns. Published by Elsevier Inc. C1 [Lee, Cara; Jones, Alexis; Kainz, Danielle; Khan, Faatima; Carrithers, Michael D.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Lee, Cara; Jones, Alexis; Kainz, Danielle; Khan, Faatima; Carrithers, Michael D.] Univ Wisconsin, Dept Pathol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Lee, Cara; Jones, Alexis; Kainz, Danielle; Khan, Faatima; Carrithers, Michael D.] Univ Wisconsin, Program Cellular & Mol Pathol, Sch Med & Publ Hlth, Madison, WI USA. [Carrithers, Michael D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Carrithers, MD (reprint author), Univ Illinois, Coll Med, Dept Neurol, 912 South Wood, Chicago, IL 60612 USA. EM mcar1@uic.edu OI Lee, Cara/0000-0003-0614-9060 FU U.S. Department of Veterans Affairs [2 I01 BX000467-05] FX This work was supported by a Merit Award (BLR&D, 2 I01 BX000467-05) from the U.S. Department of Veterans Affairs. NR 16 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 7 PY 2015 VL 463 IS 4 BP 1203 EP 1209 DI 10.1016/j.bbrc.2015.06.085 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CN5FN UT WOS:000358455300116 PM 26086103 ER PT J AU Trousil, S Zheng, B AF Trousil, Sebastian Zheng, Bin TI Addicted to AA (Acetoacetate): A Point of Convergence between Metabolism and BRAF Signaling SO MOLECULAR CELL LA English DT Editorial Material ID CELL PROLIFERATION; MELANOMA; PATHWAY C1 [Trousil, Sebastian; Zheng, Bin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA 02115 USA. RP Zheng, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA 02115 USA. EM bin.zheng@cbrc2.mgh.harvard.edu FU NCI NIH HHS [R01 CA166717] NR 10 TC 0 Z9 0 U1 0 U2 1 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 AUG 6 PY 2015 VL 59 IS 3 BP 333 EP 334 DI 10.1016/j.molcel.2015.07.024 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CT0BB UT WOS:000362457600001 PM 26253025 ER PT J AU Treon, SP AF Treon, Steven P. TI How I treat Waldenstrom macroglobulinemia SO BLOOD LA English DT Review ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; COOPERATIVE-ONCOLOGY-GROUP; L265P SOMATIC MUTATION; IGM MULTIPLE-MYELOMA; NON-HODGKIN-LYMPHOMA; ANTI-MAG NEUROPATHY; MYD88 L265P; RITUXIMAB THERAPY; IMMUNOGLOBULIN-M AB Waldenstrom macroglobulinemia (WM) is a B-cell neoplasm manifested by the accumulation of clonal immunoglobulin (Ig)M-secreting lymphoplasmacytic cells. MYD88 and CXCR4 warts, hypogammaglobulinemia, infections, myelokathexis syndrome-like somatic mutations are present in >90% and 30% to 35% of WM patients, respectively, and impact disease presentation, treatment outcome, and overall survival. Familial predisposition is common in WM. Asymptomatic patients should be observed. Patients with disease-related hemoglobin <10 g/L, platelets <100 x 109/L, bulky adenopathy and/or organomegaly, symptomatic hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia, cold-agglutinin disease, or transformed disease should be considered for therapy. Plasmapheresis should be used for patients with symptomatic hyperviscosity and before rituximab for those with high serum IgM levels to preempt a symptomatic IgM flare. Treatment choice should take into account specific goals of therapy, necessity for rapid disease control, risk of treatment-related neuropathy, immunosuppression and secondary malignancies, and planning for future autologous stem cell transplantation. Frontline treatments include rituximab alone or rituximab combined with alkylators (bendamustine and cyclophosphamide), proteasome inhibitors (bortezomib and carfilzomib), nucleoside analogs (fludarabine and cladribine), and ibrutinib. In the salvage setting, an alternative frontline regimen, ibrutinib, everolimus, or stem cell transplantation can be considered. Investigational therapies under development for WM include agents that target MYD88, CXCR4, BCL2, and CD27/CD70 signaling, novel proteasome inhibitors, and chimeric antigen receptor-modified T-cell therapy. C1 [Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Treon, Steven P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M548,450 Brookline Ave, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu FU Linda and Edward Nelson Endowment for Studies into Waldenstrom Macroglobulienmia; Kerry Robertson Fund for Waldenstrom's Research; Bauman Family Foundation; International Waldenstrom's Macroglobulinemia Foundation FX This work was supported by Peter S. Bing, M.D., the Linda and Edward Nelson Endowment for Studies into Waldenstrom Macroglobulienmia, the Kerry Robertson Fund for Waldenstrom's Research, the Bauman Family Foundation, and the International Waldenstrom's Macroglobulinemia Foundation. NR 122 TC 24 Z9 25 U1 1 U2 9 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 AUG 6 PY 2015 VL 126 IS 6 BP 721 EP 732 DI 10.1182/blood-2015-01-553974 PG 12 WC Hematology SC Hematology GA CQ3RG UT WOS:000360519600007 PM 26002963 ER PT J AU Vivante, A Kleppa, MJ Schulz, J Kohl, S Sharma, A Chen, J Shril, S Hwang, DY Weiss, AC Kaminski, MM Shukrun, R Kemper, MJ Lehnhardt, A Beetz, R Sanna-Cherchi, S Verbitsky, M Gharavi, AG Stuart, HM Feather, SA Goodship, JA Goodship, THJ Woolf, AS Westra, SJ Doody, DP Bauer, SB Lee, RS Adam, RM Lu, W Reutter, HM Kehinde, EO Mancini, EJ Lifton, RP Tasic, V Lienkamp, SS Juppner, H Kispert, A Hildebrandt, F AF Vivante, Asaf Kleppa, Marc-Jens Schulz, Julian Kohl, Stefan Sharma, Amita Chen, Jing Shril, Shirlee Hwang, Daw-Yang Weiss, Anna-Carina Kaminski, Michael M. Shukrun, Rachel Kemper, Markus J. Lehnhardt, Anja Beetz, Rolf Sanna-Cherchi, Simone Verbitsky, Miguel Gharavi, All G. Stuart, Helen M. Feather, Sally A. Goodship, Judith A. Goodship, Timothy H. J. Woolf, Adrian S. Westra, Sjirk J. Doody, Daniel P. Bauer, Stuart B. Lee, Richard S. Adam, Rosalyn M. Lu, Weining Reutter, Heiko M. Kehinde, Elijah O. Mancini, Erika J. Lifton, Richard P. Tasic, Velibor Lienkamp, Soeren S. Jueppner, Harald Kispert, Andreas Hildebrandt, Friedhelm TI Mutations in TBX18 Cause Dominant Urinary Tract Malformations via Transcriptional Dysregulation of Ureter Development SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CONGENITAL-ANOMALIES; KIDNEY; CILIOPATHY; EXPRESSION; DISEASE; GENES; DISRUPTION; DISORDERS; DOMAIN; CAKUT AB Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first three decades of life. Identification of single-gene mutations that cause CAKUT permits the first insights into related disease mechanisms. However, for most cases the underlying defect remains elusive. We identified a kindred with an autosomal-dominant form of CAKUT with predominant ureteropelvic junction obstruction. By whole exome sequencing, we identified a heterozygous truncating mutation (c.1010delG) of T-Box transcription factor 18 (TBX18) in seven affected members of the large kindred. A screen of additional families with CAKUT identified three families harboring two heterozygous TBX18 mutations (c.1570C>T and c.487A>G). TBX18 is essential for developmental specification of the ureteric mesenchyme and ureteric smooth muscle cells. We found that all three TBX18 altered proteins still dimerized with the wild-type protein but had prolonged protein half life and exhibited reduced transcriptional repression activity compared to wild-type TBX18. The p.Lys163Glu substitution altered an amino acid residue critical for TBX18-DNA interaction, resulting in impaired TBX18-DNA binding. These data indicate that dominant-negative TBX18 mutations cause human CAKUT by interference with TBX18 transcriptional repression, thus implicating ureter smooth muscle cell development in the pathogenesis of human CAKUT. C1 [Vivante, Asaf; Schulz, Julian; Kohl, Stefan; Chen, Jing; Shril, Shirlee; Hwang, Daw-Yang; Shukrun, Rachel; Hildebrandt, Friedhelm] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Vivante, Asaf] Sheba Med Ctr, Talpiot Med Leadership Program, IL-52621 Tel Hashomer, Israel. [Kleppa, Marc-Jens; Weiss, Anna-Carina; Kispert, Andreas] Hannover Med Sch, Inst Molbiol, D-30625 Hannover, Germany. [Sharma, Amita] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediatr Nephrol Unit, Boston, MA 02114 USA. [Sharma, Amita] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Sharma, Amita; Doody, Daniel P.; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hwang, Daw-Yang] Kaohsiung Med Univ, Div Nephrol, Dept Med, Kaohsiung Med Univ Hosp, Kaohsiung 807, Taiwan. [Kaminski, Michael M.; Lienkamp, Soeren S.] Univ Freiburg, Med Ctr, Dept Med, Div Renal, D-79106 Freiburg, Germany. [Kemper, Markus J.; Lehnhardt, Anja] Univ Med Ctr Hamburg Eppendorf, Dept Pediat, D-20246 Hamburg, Germany. [Beetz, Rolf] Univ Med Clin, Ctr Pediat & Adolescent Med, D-55131 Mainz, Germany. [Sanna-Cherchi, Simone; Verbitsky, Miguel; Gharavi, All G.] Columbia Univ, Dept Med, New York, NY 10023 USA. [Stuart, Helen M.; Woolf, Adrian S.] Univ Manchester, Inst Human Dev, Fac Med & Human Sci, Manchester Acad Hlth Sci Ctr, Manchester M13 9WL, Lancs, England. [Stuart, Helen M.; Woolf, Adrian S.] Royal Manchester Childrens & St Marys Hosp, Manchester M13 9WL, Lancs, England. [Feather, Sally A.] Leeds Teaching Hosp NHS Trust, Leeds LS1 3EX, W Yorkshire, England. [Goodship, Judith A.; Goodship, Timothy H. J.] Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Westra, Sjirk J.] Harvard Univ, Sch Med, Pediat Radiol Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Doody, Daniel P.] Harvard Univ, Sch Med, Dept Pediat Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bauer, Stuart B.; Lee, Richard S.; Adam, Rosalyn M.] Harvard Univ, Sch Med, Dept Urol, Boston Childrens Hosp, Boston, MA 02114 USA. [Lu, Weining] Boston Univ, Med Ctr, Renal Sect, Dept Med, Boston, MA 02118 USA. [Reutter, Heiko M.] Univ Bonn, Dept Neonatol, Childrens Hosp, D-53127 Bonn, Germany. [Kehinde, Elijah O.] Kuwait Univ, Div Urol, Dept Surg, Safat 13110, Kuwait. [Mancini, Erika J.] Univ Oxford, Div Struct Biol, Wellcome Trust Ctr Human Genet, Oxford 0X3 7BN, England. [Mancini, Erika J.] Univ Sussex, Sch Life Sci, Brighton BN1 9QD, E Sussex, England. [Lifton, Richard P.] Yale Univ, Sch Med, Dept Human Genet, New Haven, CT 06510 USA. [Lifton, Richard P.; Hildebrandt, Friedhelm] Howard Hughes Med Inst, Skopje 1000, Macedonia. [Tasic, Velibor] Univ Childrens Hosp, Med Sch Skopje, Skopje 1000, Macedonia. [Lienkamp, Soeren S.] Ctr Biol Signaling Studies BIOSS, D-79104 Freiburg, Germany. RP Hildebrandt, F (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Med, Boston, MA 02115 USA. EM friedhelm.hildebrandt@childrens.harvard.edu RI Mancini, Erika/J-9880-2013; OI Mancini, Erika/0000-0001-9591-7898; Stuart, Helen/0000-0003-2569-235X; Woolf, Adrian/0000-0001-5541-1358 FU NIH [DK096238, 5U54HG006504, DK 46718, DK078226, DK088767]; March of Dimes; German Research Foundation (DFG) [SFB1140]; Emmy Noether programme; Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy) at Hannover Medical School; Kidney Research UK; Medical Research Council [G0600040, MR/L002744/1]; Wellcome Trust [066647]; NIHR UK; Fulbright postdoctoral scholar award; Boston Children's Hospital; [Ki72817-1] FX We are grateful the families who contributed to this study. We thank Seymour Rosen, Heather J. Cordell, William G. Newman, Stanley Swierzewski III, Frank Croke, John Blanchete, Dicken Ko, Ghaleb Daouk, John Herrin, and the UK VUR Study Group for contributing renal pathology, radiology, and clinical materials. This research was supported by grants from the NIH to R.S.L. (DK096238), to R.P.L. (5U54HG006504), to H.J. (DK 46718), to W.L. (DK078226), and to F.H. (DK088767) and from the March of Dimes to W.L. and F.H. This work was supported by grants from the German Research Foundation (DFG) to S.S.L. within SFB1140 and the Emmy Noether programme and to A.K. by an individual grant (Ki72817-1) and within the Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy) at Hannover Medical School. A.S.W. received project grants from Kidney Research UK, the Medical Research Council (G0600040 and MR/L002744/1), and the Wellcome Trust (066647). H.M.S. was funded by fellowships from NIHR UK and the Wellcome Trust. A.S.W.'s and H.M.S.'s research was facilitated by the Manchester Academic Health Sciences Centre. A.V. is a recipient of a Fulbright postdoctoral scholar award and of a Manton Center fellowship award from Boston Children's Hospital. F.H. and R.P.L. are Investigators of the Howard Hughes Medical Institute. F.H. is the Warren E. Grupe Professor of Pediatrics at Harvard Medical School. NR 34 TC 7 Z9 11 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG 6 PY 2015 VL 97 IS 2 BP 291 EP 301 DI 10.1016/j.ajhg.2015.07.001 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA CO7GY UT WOS:000359328800009 PM 26235987 ER PT J AU Sequist, LV Rolfe, L Allen, AR AF Sequist, Lecia V. Rolfe, Lindsey Allen, Andrew R. TI Rociletinib in EGFR-Mutated Non-Small-Cell Lung Cancer REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rolfe, Lindsey] Clovis Oncol, Cambridge, England. [Allen, Andrew R.] Clovis Oncol, San Francisco, CA USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM lvsequist@partners.org NR 0 TC 14 Z9 15 U1 2 U2 5 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 AUG 6 PY 2015 VL 373 IS 6 BP 578 EP 579 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CO2LM UT WOS:000358987700021 PM 26244318 ER PT J AU Faraone, SV Asherson, P Banaschewski, T Biederman, J Buitelaar, JK Ramos-Quiroga, JA Rohde, LA Sonuga-Barke, EJS Tannock, R Franke, B AF Faraone, Stephen V. Asherson, Philip Banaschewski, Tobias Biederman, Joseph Buitelaar, Jan K. Ramos-Quiroga, Josep Antoni Rohde, Luis Augusto Sonuga-Barke, Edmund J. S. Tannock, Rosemary Franke, Barbara TI Attention-deficit/hyperactivity disorder SO NATURE REVIEWS DISEASE PRIMERS LA English DT Article ID DEFICIT-HYPERACTIVITY-DISORDER; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIALS; SUBSTANCE-USE DISORDERS; GUANFACINE EXTENDED-RELEASE; COGNITIVE-BEHAVIORAL THERAPY; SCHOOL-BASED INTERVENTIONS; EMOTIONAL SELF-REGULATION; AUTISM SPECTRUM DISORDER; AGE-DEPENDENT DECLINE AB Attention-deficit/hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder that affects 5% of children and adolescents and 2.5% of adults worldwide. Throughout an individual's lifetime, ADHD can increase the risk of other psychiatric disorders, educational and occupational failure, accidents, criminality, social disability and addictions. No single risk factor is necessary or sufficient to cause ADHD. In most cases ADHD arises from several genetic and environmental risk factors that each have a small individual effect and act together to increase susceptibility. The multifactorial causation of ADHD is consistent with the heterogeneity of the disorder, which is shown by its extensive psychiatric co-morbidity, its multiple domains of neurocognitive impairment and the wide range of structural and functional brain anomalies associated with it. The diagnosis of ADHD is reliable and valid when evaluated with standard criteria for psychiatric disorders. Rating scales and clinical interviews facilitate diagnosis and aid screening. The expression of symptoms varies as a function of patient developmental stage and social and academic contexts. Although there are no curative treatments for ADHD, evidenced-based treatments can markedly reduce its symptoms and associated impairments. For example, medications are efficacious and normally well tolerated, and various non-pharmacological approaches are also valuable. Ongoing clinical and neurobiological research holds the promise of advancing diagnostic and therapeutic approaches to ADHD. For an illustrated summary of this Primer, C1 [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY 13210 USA. [Faraone, Stephen V.] Univ Bergen, Dept Biomed, KG Jebsen Ctr Neuropsychiat Disorders, N-5020 Bergen, Norway. [Asherson, Philip] Kings Coll London, Social Genet & Dev Psychiat, Inst Psychiat Psychol & Neurosci, London, England. [Banaschewski, Tobias] Heidelberg Univ, Med Fac Mannheim, Dept Child & Adolescent Psychiat & Psychot, Cent Inst Mental Hlth, Mannheim, Germany. [Biederman, Joseph] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Buitelaar, Jan K.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Med Ctr, Nijmegen, Netherlands. [Buitelaar, Jan K.] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands. [Ramos-Quiroga, Josep Antoni] Hosp Univ Vall Hebron, Dept Psychiat, ADHD Program, Barcelona, Spain. [Ramos-Quiroga, Josep Antoni] CIBERSAM, Biomed Network Res Ctr Mental Hlth, Barcelona, Spain. [Ramos-Quiroga, Josep Antoni] Univ Autonoma Barcelona, Dept Psychiat & Legal Med, Barcelona, Spain. [Rohde, Luis Augusto] Univ Fed Rio Grande do Sul, Dept Psychiat, Hosp Clin Porto Alegre, ADHD Outpatient Program, Porto Alegre, RS, Brazil. [Rohde, Luis Augusto] Natl Inst Dev Psychiat Children & Adolescents, Sao Paulo, Brazil. [Sonuga-Barke, Edmund J. S.] Univ Southampton, Dept Psychol, Southampton, Hants, England. [Sonuga-Barke, Edmund J. S.] Univ Ghent, Dept Expt Clin & Hlth Psychol, Ghent, Belgium. [Tannock, Rosemary] Hosp Sick Children, Res Inst, Neurosci & Mental Hlth Res Program, Toronto, ON, Canada. [Tannock, Rosemary] Univ Toronto, Dept Appl Psychol & Human Dev, Ontario Inst Studies Educ, Toronto, ON, Canada. [Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Human Genet, Nijmegen, Netherlands. [Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Psychiat, Nijmegen, Netherlands. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. EM sfaraone@childpsychresearch.org RI Franke, Barbara/D-4836-2009 OI Franke, Barbara/0000-0003-4375-6572 FU K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway; European Commission [602805, 278948, 602450, 603016, 643051, 642996, 260576]; National Institute of Mental Health (NIMH) [R13MH059126, R01MH094469]; Netherlands Organization for Health Research and Development [ZonMw 60-60600-97-193]; Netherlands Organization for Scientific Research (NWO) [1750102007010, 433-09-242, 056-13-015]; US NIH Consortium grant - cross-NIH alliance funds Big Data to Knowledge Centers of Excellence [U54 EB020403]; NWO [433-09-229, 016-130-669]; NIH Consortium grant - cross-NIH alliance funds Big Data to Knowledge Centers of Excellence [U54 EB020403]; Departament de Salut, Government of Catalonia, Spain, Instituto de Salud Carlos III-FIS [PI12/01139]; Plan Nacional Sobre Drogas [PNSD2011/0080]; Canadian Institutes for Health Research (CIHR) [245899]; Institute of Education Sciences [R305A120184]; National Counsel of Technological and Scientific Development - CNPq [304678/2010-4]; Economic Social Research Council [ES/I037970/1]; Medical Research Council [MR/K022474/1]; National Institute for Health Research [NIHR PGfAR - RP-PG-0108-10061]; MQ Transforming Mental Health [MQ14PP_83]; Shire Pharmaceuticals FX The authors thank M. Mehta for help with incorporating the default mode network into Figure 4. S.V.F. is supported by the K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway, the European Commission's Seventh Framework programme (FP7/2007-2013) under grant agreement no. 602805 and National Institute of Mental Health (NIMH) grants R13MH059126 and R01MH094469. J.B. is supported by grants from the Netherlands Organization for Health Research and Development (ZonMw 60-60600-97-193), the Netherlands Organization for Scientific Research (NWO; grants 1750102007010, 433-09-242 and 056-13-015), and by the European Commission's Seventh Framework programme (FP7/2007-2013) under grant agreement no. 278948 (TACTICS), 602450 (IMAGEMEND), 602805 (AGGRESSOTYPE) and 603016 (MATRICS); and Horizon 2020 research programme (grant agreement no. 643051 (MiND) and 642996 (BRAINVIEW)). His research also receives funding from the US NIH Consortium grant no. U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centers of Excellence. B.F. is supported by grants from NWO (grants no. 433-09-229 and 016-130-669), from the European Commission's Seventh Framework programme (grant agreement no. 278948 (TACTICS), 602450 (IMAGEMEND) and 602805 (Aggressotype)); and Horizon 2020 research programme (grant agreement no. 643051 (MiND)). Her research also receives funding from the NIH Consortium grant no. U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centers of Excellence. J.A.R.-Q. is supported by grants from and Departament de Salut, Government of Catalonia, Spain, Instituto de Salud Carlos III-FIS (PI12/01139), Plan Nacional Sobre Drogas (PNSD2011/0080) and the European Commission's Seventh Framework programme. R.T. is supported by grants from the Canadian Institutes for Health Research (CIHR #245899) and the Institute of Education Sciences (R305A120184). L.A.R. is supported by a grant from the National Counsel of Technological and Scientific Development - CNPq (grant no. 304678/2010-4). E.J.S.S.-B. is supported by grants from the Economic Social Research Council (ES/I037970/1), Medical Research Council (MR/K022474/1), National Institute for Health Research (NIHR PGfAR - RP-PG-0108-10061), MQ Transforming Mental Health (MQ14PP_83), European Commission's Seventh Framework programme (2007-2013) under grant agreement no. 260576 and an unrestricted programme grant from Shire Pharmaceuticals. NR 254 TC 38 Z9 38 U1 30 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2056-676X J9 NAT REV DIS PRIMERS JI Nat. Rev. Dis. Primers PD AUG 6 PY 2015 VL 1 AR 15020 DI 10.1038/nrdp.2015.20 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA DT2LC UT WOS:000381310800001 PM 27189265 ER PT J AU Liu, K Jounaidi, Y Forman, SA Feng, HJ AF Liu, K. Jounaidi, Y. Forman, S. A. Feng, H. -J. TI ETOMIDATE UNIQUELY MODULATES THE DESENSITIZATION OF RECOMBINANT alpha 1 beta 3 delta GABA(A) RECEPTORS SO NEUROSCIENCE LA English DT Article DE GABA(A) receptors; d subunit; concatemers; etomidate; desensitization; deactivation ID DELTA-SUBUNIT; A RECEPTORS; TRANSMEMBRANE DOMAIN; HIPPOCAMPAL-NEURONS; TONIC INHIBITION; GAMMA; CURRENTS; STOICHIOMETRY; ALPHA-4-BETA-3-DELTA; GABA(A)-RECEPTOR AB Central GABA(A) receptors mediate GABAergic phasic and tonic inhibition. While synaptic alpha beta gamma GABA(A) receptors primarily mediate phasic inhibition, extrasynaptic alpha beta delta receptors play an important role in mediating tonic inhibition. Etomidate is a general anesthetic that produces its effects by enhancing GABA(A) receptor activity. We previously showed that etomidate modulates the gating of oocyte-expressed alpha beta gamma and alpha beta delta receptors with similar overall allosteric impact, but different pharmacological patterns. In alpha beta gamma receptors, etomidate enhances apparent GABA sensitivity (reduces GABA EC50), modestly increases maximal GABA efficacy, and slows current deactivation without affecting desensitization (Zhong et al., 2008). In alpha beta delta receptors characterized by low GABA efficacy, etomidate dramatically increases responses to both low and maximal GABA. The effects of etomidate on desensitization and deactivation of alpha beta delta receptors are unknown. To investigate the kinetic effects of etomidate on alpha 1 beta 3 delta receptors of defined subunit arrangement, we expressed concatenated trimer (beta 3-alpha 1-delta) and dimer (beta 3-alpha 1) GABA(A) receptor subunit assemblies in human embryonic kidney (HEK)293T cells and recorded whole-cell voltage-clamp currents during rapid external solution exchanges. As expected, etomidate substantially increased maximal GABA-induced currents and prolonged deactivation. Moreover, desensitization was significantly decreased by etomidate. During prolonged GABA applications, etomidate enhanced steady-state currents more than peak currents. Thus, etomidate enhances tonic GABAergic inhibition through extrasynaptic alpha beta delta receptors by both augmenting gating and reducing desensitization. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Liu, K.; Jounaidi, Y.; Forman, S. A.; Feng, H. -J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Liu, K.; Jounaidi, Y.; Forman, S. A.; Feng, H. -J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Liu, K.] China Japan Friendship Hosp, Dept Anesthesia, Beijing, Peoples R China. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM saforman@mgh.harvard.edu; feng.huajun@mgh.harvard.edu FU National Institutes of Health National Institute of General Medical Sciences [R01 GM089745, P01 GM058448]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX This work was supported by National Institutes of Health National Institute of General Medical Sciences (R01 GM089745 and P01 GM058448) to S.A.F. We thank the support from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. NR 43 TC 0 Z9 0 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD AUG 6 PY 2015 VL 300 BP 307 EP 313 DI 10.1016/j.neuroscience.2015.05.051 PG 7 WC Neurosciences SC Neurosciences & Neurology GA CL2IQ UT WOS:000356767400029 PM 26028470 ER PT J AU Bolo, NR Musen, G Simonson, DC Nickerson, LD Flores, VL Siracusa, T Hager, B Lyoo, IK Renshaw, PF Jacobson, AM AF Bolo, Nicolas R. Musen, Gail Simonson, Donald C. Nickerson, Lisa D. Flores, Veronica L. Siracusa, Tamar Hager, Brandon Lyoo, In Kyoon Renshaw, Perry F. Jacobson, Alan M. TI Functional Connectivity of Insula, Basal Ganglia, and Prefrontal Executive Control Networks during Hypoglycemia in Type 1 Diabetes SO JOURNAL OF NEUROSCIENCE LA English DT Article DE executive control resting-state network; functional connectivity; functional magnetic resonance imaging; hypoglycemia; independent component analysis; type 1 diabetes ID INDEPENDENT COMPONENT ANALYSIS; HUMAN BRAIN; SPONTANEOUS FLUCTUATIONS; METABOLISM; GLUTAMATE; ACTIVATION; AWARENESS; DISEASE; ADULTS; VARIABILITY AB Human brain networks mediating interoceptive, behavioral, and cognitive aspects of glycemic control are not well studied. Using group independent component analysis with dual-regression approach of functional magnetic resonance imaging data, we examined the functional connectivity changes of large-scale resting state networks during sequential euglycemic-hypoglycemic clamp studies in patients with type 1 diabetes and nondiabetic controls and how these changes during hypoglycemia were related to symptoms of hypoglycemia awareness and to concurrent glycosylated hemoglobin (HbA1c) levels. During hypoglycemia, diabetic patients showed increased functional connectivity of the right anterior insula and the prefrontal cortex within the executive control network, which was associated with higher HbA1c. Controls showed decreased functional connectivity of the right anterior insula with the cerebellum/basal ganglia network and of temporal regions within the temporal pole network and increased functional connectivity in the default mode and sensorimotor networks. Functional connectivity reductions in the right basal ganglia were correlated with increases of self-reported hypoglycemic symptoms in controls but not in patients. Resting state networks that showed different group functional connectivity during hypoglycemia may be most sensitive to glycemic environment, and their connectivity patterns may have adapted to repeated glycemic excursions present in type 1 diabetes. Our results suggest that basal ganglia and insula mediation of interoceptive awareness during hypoglycemia is altered in type 1 diabetes. These changes could be neuroplastic adaptations to frequent hypoglycemic experiences. Functional connectivity changes in the insula and prefrontal cognitive networks could also reflect an adaptation to changes in brain metabolic pathways associated with chronic hyperglycemia. C1 [Bolo, Nicolas R.; Nickerson, Lisa D.; Siracusa, Tamar; Renshaw, Perry F.] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. [Bolo, Nicolas R.; Musen, Gail; Simonson, Donald C.; Nickerson, Lisa D.; Renshaw, Perry F.; Jacobson, Alan M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Musen, Gail; Flores, Veronica L.; Jacobson, Alan M.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Simonson, Donald C.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Hager, Brandon] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Lyoo, In Kyoon] Ewha Womans Univ, Ewha Brain Inst, Seoul 120750, South Korea. [Lyoo, In Kyoon] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul 120750, South Korea. [Jacobson, Alan M.] Winthrop Univ Hosp, Res Inst, Mineola, NY 11501 USA. RP Musen, G (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM nbolo@bidmc.harvard.edu; gail.musen@joslin.harvard.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK073843, DK-60754, DK-62218-01A1, P30-DK-36836]; Herbert Graetz Fund FX This work was supported in part by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grants R01-DK073843, DK-60754, DK-62218-01A1, and P30-DK-36836 (Joslin Diabetes and Endocrinology Research Center) and the Herbert Graetz Fund. We thank Judi Lauerman (Brigham and Women's Hospital, Boston, MA) and Karen Branch (Massachusetts General Hospital, Boston, MA) for their expert nursing assistance. Parts of this article were presented at the First Scientific Sessions of the American Diabetes Association Research Symposium: Diabetes and the Brain, Alexandria, VA, October 28 - 30, 2011, and at the 72nd Scientific Sessions of the American Diabetes Association, Philadelphia, PA, June 8 - 12, 2012. NR 44 TC 3 Z9 4 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 5 PY 2015 VL 35 IS 31 BP 11012 EP 11023 DI 10.1523/JNEUROSCI.0319-15.2015 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CR2CH UT WOS:000361131800009 PM 26245963 ER PT J AU Leijenaar, RTH Nalbantov, G Carvalho, S van Elmpt, WJC Troost, EGC Boellaard, R Aerts, HJWL Gillies, RJ Lambin, P AF Leijenaar, Ralph T. H. Nalbantov, Georgi Carvalho, Sara van Elmpt, Wouter J. C. Troost, Esther G. C. Boellaard, Ronald Aerts, Hugo J. W. L. Gillies, Robert J. Lambin, Philippe TI The effect of SUV discretization in quantitative FDG-PET Radiomics: the need for standardized methodology in tumor texture analysis SO SCIENTIFIC REPORTS LA English DT Article ID CELL LUNG-CANCER; F-18-FDG PET; UPTAKE HETEROGENEITY; RESPONSE ASSESSMENT; RADIOTHERAPY; FEATURES; IMAGES; CARCINOMA; STAGE; QUANTIFICATION AB FDG-PET-derived textural features describing intra-tumor heterogeneity are increasingly investigated as imaging biomarkers. As part of the process of quantifying heterogeneity, image intensities (SUVs) are typically resampled into a reduced number of discrete bins. We focused on the implications of the manner in which this discretization is implemented. Two methods were evaluated: (1) RD, dividing the SUV range into D equally spaced bins, where the intensity resolution (i.e. bin size) varies per image; and (2) RB, maintaining a constant intensity resolution B. Clinical feasibility was assessed on 35 lung cancer patients, imaged before and in the second week of radiotherapy. Forty-four textural features were determined for different D and B for both imaging time points. Feature values depended on the intensity resolution and out of both assessed methods, RB was shown to allow for a meaningful inter-and intra-patient comparison of feature values. Overall, patients ranked differently according to feature values-which was used as a surrogate for textural feature interpretation-between both discretization methods. Our study shows that the manner of SUV discretization has a crucial effect on the resulting textural features and the interpretation thereof, emphasizing the importance of standardized methodology in tumor texture analysis. C1 [Leijenaar, Ralph T. H.; Nalbantov, Georgi; Carvalho, Sara; van Elmpt, Wouter J. C.; Troost, Esther G. C.; Aerts, Hugo J. W. L.; Lambin, Philippe] MUMC, GROW Sch Oncol & Dev Biol, Dept Radiat Oncol MAASTRO, Maastricht, Netherlands. [Boellaard, Ronald] Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Radiat Oncol, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Radiol, Boston, MA 02115 USA. [Gillies, Robert J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Imaging & Metab, Tampa, FL 33612 USA. RP Leijenaar, RTH (reprint author), MUMC, GROW Sch Oncol & Dev Biol, Dept Radiat Oncol MAASTRO, Maastricht, Netherlands. EM ralph.leijenaar@maastro.nl RI Aerts, Hugo/P-6350-2015; OI Aerts, Hugo/0000-0002-2122-2003; Boellaard, Ronald/0000-0002-0313-5686; Troost, Esther/0000-0001-9550-9050 FU QuIC-ConCePT project; EFPIA companies; Innovative Medicine Initiative Joint Undertaking (IMI JU) [115151]; National Institute of Health [NIH-USA U01 CA 143062-01]; CTMM framework (AIRFORCE project) [030-103]; EU; euroCAT (IVA Interreg) FX The authors acknowledge the support of the QuIC-ConCePT project, partly funded by EFPIA companies and the Innovative Medicine Initiative Joint Undertaking (IMI JU) under Grant Agreement No. 115151. Authors also acknowledge financial support from the National Institute of Health (NIH-USA U01 CA 143062-01, Radiomics of NSCLC), the CTMM framework (AIRFORCE project, grant 030-103), EU 6th and 7th framework program (EUROXY, METOXIA, EURECA, ARTFORCE), euroCAT (IVA Interreg - www.eurocat.info), SME Phase 2 (EU proposal 673780 - RAIL), Alpe d'HuZes-KWF (DESIGN), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society (KWF UM 2011-5020, KWF UM 2009-4454). NR 44 TC 32 Z9 32 U1 8 U2 23 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 AUG 5 PY 2015 VL 5 AR 11075 DI 10.1038/srep11075 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO4NI UT WOS:000359137200001 PM 26242464 ER PT J AU Moyer, CE Shelton, MA Sweet, RA AF Moyer, Caitlin E. Shelton, Micah A. Sweet, Robert A. TI Dendritic spine alterations in schizophrenia SO NEUROSCIENCE LETTERS LA English DT Review DE Schizophrenia; Dendritic spine; Postmortem; Adolescence; MAP2; Kalirin ID MICROTUBULE-ASSOCIATED PROTEINS; LIGHT-CHAIN PHOSPHORYLATION; CORTICAL PYRAMIDAL NEURONS; PRIMATE CEREBRAL-CORTEX; PREFRONTAL CORTEX; PSYCHIATRIC-DISORDERS; SYNAPTIC PLASTICITY; MASS-SPECTROMETRY; MAP2 EXPRESSION; EARLY ADULTHOOD AB Schizophrenia is a chronic illness affecting approximately 0.5-1% of the world's population. The etiology of schizophrenia is complex, including multiple genes, and contributing environmental effects that adversely impact neurodevelopment. Nevertheless, a final common result, present in many subjects with schizophrenia, is impairment of pyramidal neuron dendritic morphology in multiple regions of the cerebral cortex. In this review, we summarize the evidence of reduced dendritic spine density and other dendritic abnormalities in schizophrenia, evaluate current data that informs the neurodevelopment timing of these impairments, and discuss what is known about possible upstream sources of dendritic spine loss in this illness. Published by Elsevier Ireland Ltd. C1 [Moyer, Caitlin E.; Shelton, Micah A.; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA 15206 USA. RP Sweet, RA (reprint author), Biomed Sci Tower,Rm W-1645 3811 OHara St, Pittsburgh, PA 15240 USA. EM sweetra@upmc.edu FU National Institutes of Health [MH071533, MH103204, 5T32NS007433] FX This work was supported in part by National Institutes of Health grants MH071533, MH103204, and 5T32NS007433. 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 94 TC 12 Z9 13 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 5 PY 2015 VL 601 BP 46 EP 53 DI 10.1016/j.neulet.2014.11.042 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CN5HR UT WOS:000358460900007 PM 25478958 ER PT J AU Park, E Graziano, BR Zheng, W Garabedian, M Goode, BL Eck, MJ AF Park, Eunyoung Graziano, Brian R. Zheng, Wei Garabedian, Mikael Goode, Bruce L. Eck, Michael J. TI Structure of a Bud6/Actin Complex Reveals a Novel WH2-like Actin Monomer Recruitment Motif SO STRUCTURE LA English DT Article ID FORMIN HOMOLOGY-2 DOMAIN; NUCLEATION-PROMOTING FACTOR; FILAMENT NUCLEATION; S. CEREVISIAE; MECHANISM; SPIRE; MDIA1; ELONGATION; PROTEINS; PROFILIN AB In budding yeast, the actin-binding protein Bud6 cooperates with formins Bni1 and Bnr1 to catalyze the assembly of actin filaments. The nucleation-enhancing activity of Bud6 requires both a "core'' domain that binds to the formin and a "flank'' domain that binds monomeric actin. Here, we describe the structure of the Bud6 flank domain in complex with actin. Two helices in Bud6 flank interact with actin; one binds in a groove at the barbed end of the actin monomer in a manner closely resembling the helix of WH2 domains, a motif found in many actin nucleation factors. The second helix rises along the face of actin. Mutational analysis verifies the importance of these Bud6-actin contacts for nucleation-enhancing activity. The Bud6 binding site on actin overlaps with that of the formin FH2 domain and is also incompatible with inter-subunit contacts in F-actin, suggesting that Bud6 interacts only transiently with actin monomers during filament nucleation. C1 [Park, Eunyoung; Zheng, Wei; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Park, Eunyoung; Zheng, Wei; Eck, Michael J.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02215 USA. [Graziano, Brian R.; Garabedian, Mikael; Goode, Bruce L.] Brandeis Univ, Dept Biol, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA. RP Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, SM1036,450 Brookline Ave, Boston, MA 02215 USA. EM eck@crystal.harvard.edu OI Graziano, Brian/0000-0003-1081-908X FU NIH [GM071834, GM083137, P41 GM103403] FX This work was supported by NIH grants GM071834 (M.J.E.) and GM083137 (B.L.G.). We thank the staff of the Northeastern Collaborative Access Team (NE-CAT) beamlines at the Advanced Photon Source. NE-CAT is supported by a grant from the NIH (P41 GM103403). NR 48 TC 4 Z9 4 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD AUG 4 PY 2015 VL 23 IS 8 BP 1492 EP 1499 DI 10.1016/j.str.2015.05.015 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CR1VD UT WOS:000361112300014 PM 26118535 ER PT J AU Lesmes, LA Lu, ZL Baek, J Tran, N Dosher, BA Albright, TD AF Lesmes, Luis A. Lu, Zhong-Lin Baek, Jongsoo Tran, Nina Dosher, Barbara A. Albright, Thomas D. TI Developing Bayesian adapive methods for estimating sensitivity threshold (d ') in Yes-No and forced-choice tasks SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE signal detection; adaptive psychophysics; Yes-No; forced-choice; stimulus placement; rating; cuing; decision criterion ID ADAPTIVE PSYCHOMETRIC METHOD; SEQUENTIAL ESTIMATION; VISUAL-CORTEX; HUMAN-VISION; PSYCHOPHYSICAL METHOD; CONFIDENCE-INTERVALS; EXTERNAL NOISE; DISCRIMINATION; QUEST; CLASSIFICATION AB Motivated by Signal Detection Theory (SDT), we developed a family of novel adaptive methods that estimate the sensitivity threshold the signal intensity corresponding to a pre-defined sensitivity level (d' = 1) in Yes-No (YN) and Forced-Choice (FC) detection tasks. Rather than focus stimulus sampling to estimate a single level of %Yes or %Correct, the current methods sample psychometric functions more broadly, to concurrently estimate sensitivity and decision factors, and thereby estimate thresholds that are independent of decision confounds. Developed for four tasks (1) simple YN detection, (2) cued YN detection, which cues the observer's response state before each trial, (3) rated YN detection, which incorporates a Not Sure response, and (4) FC detection the qYN and qFC methods yield sensitivity thresholds that are independent of the task's decision structure (YN or FC) and/or the observer's subjective response state. Results from simulation and psychophysics suggest that 25 trials (and sometimes less) are sufficient to estimate YN thresholds with reasonable precision (s.d. = 0.10-0.15 decimal log units), but more trials are needed for FC thresholds. When the same subjects were tested across tasks of simple, cued, rated, and FC detection, adaptive threshold estimates exhibited excellent agreement with the method of constant stimuli (MCS), and with each other. These YN adaptive methods deliver criterion-free thresholds that have previously been exclusive to FC methods. C1 [Lesmes, Luis A.] Adapt Sensory Technol LLC, Boston, MA USA. [Lesmes, Luis A.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Lesmes, Luis A.; Albright, Thomas D.] Univ Calif San Diego, Dept Biol, Vis Ctr Lab, Salk Inst Biol Studies, San Diego, CA 92103 USA. [Lu, Zhong-Lin; Baek, Jongsoo; Tran, Nina] Ohio State Univ, Lab Brain Proc, Columbus, OH 43210 USA. [Dosher, Barbara A.] Univ Calif Irvine, Memory Attent & Percept Lab, Irvine, CA USA. RP Lu, ZL (reprint author), Ohio State Univ, Dept Psychol, Lab Brain Proc, 1835 Neil Ave,62 Psychol Bldg, Columbus, OH 43210 USA. EM lu.535@osu.edu FU National Eye Institute [R01 EY017491, R01 EY021553] FX The work was supported by National Eye Institute grants (R01 EY017491 and R01 EY021553). NR 62 TC 2 Z9 2 U1 1 U2 5 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD AUG 4 PY 2015 VL 6 AR 1070 DI 10.3389/fpsyg.2015.01070 PG 24 WC Psychology, Multidisciplinary SC Psychology GA CP3PH UT WOS:000359792100001 PM 26300798 ER PT J AU Warren, CR Cowan, CA AF Warren, Curtis R. Cowan, Chad A. TI Type 1 Diabetes and MicroRNA: It's Complicated SO CELL METABOLISM LA English DT Editorial Material AB Type 1 diabetes is an autoimmune disease that manifests as impaired insulin secretion, with compounding complications over time. Bhatt et al. (2015) investigate protective mechanisms in survivors of type 1 diabetes by using induced pluripotent stem cells as genetic models, uncovering novel interactions between microRNA and the DNA damage checkpoint pathway. C1 [Warren, Curtis R.; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Warren, Curtis R.; Cowan, Chad A.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Cowan, CA (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM chad_cowan@harvard.edu NR 9 TC 0 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD AUG 4 PY 2015 VL 22 IS 2 BP 202 EP 203 DI 10.1016/j.cmet.2015.07.018 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CO2QA UT WOS:000359000500005 PM 26244930 ER PT J AU Bhatt, S Gupta, MK Khamaisi, M Martinez, R Gritsenko, MA Wagner, BK Guye, P Busskamp, V Shirakawa, J Wu, GX Liew, CW Clauss, TR Valdez, I El Ouaamari, A Dirice, E Takatani, T Keenan, HA Smith, RD Church, G Weiss, R Wagers, AJ Qian, WJ King, GL Kulkarni, RN AF Bhatt, Shweta Gupta, Manoj K. Khamaisi, Mogher Martinez, Rachael Gritsenko, Marina A. Wagner, Bridget K. Guye, Patrick Busskamp, Volker Shirakawa, Jun Wu, Gongxiong Liew, Chong Wee Clauss, Therese R. Valdez, Ivan El Ouaamari, Abdelfattah Dirice, Ercument Takatani, Tomozumi Keenan, Hillary A. Smith, Richard D. Church, George Weiss, Ron Wagers, Amy J. Qian, Wei-Jun King, George L. Kulkarni, Rohit N. TI Preserved DNA Damage Checkpoint Pathway Protects against Complications in Long-Standing Type 1 Diabetes SO CELL METABOLISM LA English DT Article ID DOUBLE-STRAND BREAKS; PLURIPOTENT STEM-CELLS; VASCULAR COMPLICATIONS; PHOSPHORYLATION DYNAMICS; MRE11-RAD50-NBS1 COMPLEX; HISTONE H2AX; MECHANISMS; CHROMATIN; REPAIR; MDC1 AB The mechanisms underlying the development of complications in type 1 diabetes (T1D) are poorly understood. Disease modeling of induced pluripotent stem cells (iPSCs) from patients with longstanding T1D(disease duration >= 50 years) with severe (Medalist +C) or absent to mild complications (Medalist -C) revealed impaired growth, reprogramming, and differentiation in Medalist +C. Genomics and proteomics analyses suggested differential regulation of DNA damage checkpoint proteins favoring protection from cellular apoptosis in Medalist -C. In silico analyses showed altered expression patterns of DNA damage checkpoint factors among the Medalist groups to be targets of miR200, whose expression was significantly elevated in Medalist +C serum. Notably, neurons differentiated from Medalist +C iPSCs exhibited enhanced susceptibility to genotoxic stress that wors-ened upon miR200 overexpression. Furthermore, knockdown of miR200 in Medalist +C fibroblasts and iPSCs rescued checkpoint protein expression and reduced DNA damage. We propose miR200-regulated DNA damage checkpoint pathway as a potential therapeutic target for treating complications of diabetes. C1 [Bhatt, Shweta; Gupta, Manoj K.; Martinez, Rachael; Shirakawa, Jun; Liew, Chong Wee; Valdez, Ivan; El Ouaamari, Abdelfattah; Dirice, Ercument; Takatani, Tomozumi; Wagers, Amy J.; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Bhatt, Shweta; Gupta, Manoj K.; Khamaisi, Mogher; Shirakawa, Jun; Liew, Chong Wee; Valdez, Ivan; El Ouaamari, Abdelfattah; Dirice, Ercument; Takatani, Tomozumi; Keenan, Hillary A.; King, George L.; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Khamaisi, Mogher; Wu, Gongxiong; King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol, Boston, MA 02215 USA. [Gritsenko, Marina A.; Clauss, Therese R.; Smith, Richard D.; Qian, Wei-Jun] Pacific NW Natl Lab, Biol Sci Div, Richland, WA 99352 USA. [Wagner, Bridget K.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Guye, Patrick; Weiss, Ron] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Busskamp, Volker; Church, George] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Howard Hughes Med Inst, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu RI Smith, Richard/J-3664-2012; Busskamp, Volker/E-6339-2015; Dirice, Ercument/B-2825-2017; OI Smith, Richard/0000-0002-2381-2349; Busskamp, Volker/0000-0001-7517-8944; Shirakawa, Jun/0000-0002-0822-8750 FU NIH [RO1 DK67536, RO1 103215, UC4 DK104167-01, DP2OD006668, DP3 DK094333-01, JDRF 17-2013-310, K99DK090210, R00DK090210, 3-APF-2014-182-A-N, JDRF 10-2012-240, P41 GM103493]; Mary K. Iacocca Foundation; DOE/BER and located at Pacific Northwest National Laboratory; DOE [DE-AC05-76RL0 1830] FX The authors acknowledge the microarray facility, Children's Hospital, Boston; C. Cahill, Advanced Microscopy Facility; iPS Core Facility, DRC, Joslin Diabetes Center (NIH DK036836); and Therese Rw Clauss, Pacific Northwest National Laboratory. The authors thank G. Daley (Children's Hospital, Boston) for discussions. This research was supported in part by NIH RO1 DK67536 and NIH RO1 103215 (R.N.K.), UC4 DK104167-01 (W.J.Q., R.N.K.), DP2OD006668 (W.J.Q.), NIH DP3 DK094333-01 (G.L.K.), JDRF 17-2013-310 (H.K.), K99DK090210 and R00DK090210 (C.W.L.), 3-APF-2014-182-A-N (A.E.), JDRF 10-2012-240 (G.W.), and P41 GM103493 (R.D.S.). S.B. is the recipient of postdoctoral research fellowship from Mary K. Iacocca Foundation. Proteomics experiments were performed in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by DOE/BER and located at Pacific Northwest National Laboratory, which is operated by Battelle Memorial Institute for the DOE under Contract DE-AC05-76RL0 1830. A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies. NR 51 TC 6 Z9 6 U1 4 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD AUG 4 PY 2015 VL 22 IS 2 BP 239 EP 252 DI 10.1016/j.cmet.2015.07.015 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CO2QA UT WOS:000359000500010 PM 26244933 ER PT J AU Yudina, Z Roa, A Johnson, R Biris, N Vieira, DADA Tsiperson, V Reszka, N Taylor, AB Hart, PJ Demeler, B Diaz-Griffero, F Ivanov, DN AF Yudina, Zinaida Roa, Amanda Johnson, Rory Biris, Nikolaos Vieira, Daniel A. de Souza Aranha Tsiperson, Vladislav Reszka, Natalia Taylor, Alexander B. Hart, P. John Demeler, Borries Diaz-Griffero, Felipe Ivanov, Dmitri N. TI RING Dimerization Links Higher-Order Assembly of TRIM5 alpha to Synthesis of K63-Linked Polyubiquitin SO CELL REPORTS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; E3 UBIQUITIN LIGASE; RETROVIRAL RESTRICTION; REVERSE TRANSCRIPTION; CAPSID LATTICE; DOMAIN; REVEALS; HIV-1; PROTEIN; COMPLEX AB Members of the tripartite motif (TRIM) protein family of RING E3 ubiquitin (Ub) ligases promote innate immune responses by catalyzing synthesis of polyubiquitin chains linked through lysine 63 (K63). Here, we investigate the mechanism by which the TRIM5 alpha retroviral restriction factor activates Ubc13, the K63-linkage-specific E2. Structural, biochemical, and functional characterization of the TRIM5 alpha: Ubc13-Ub interactions reveals that activation of the Ubc13-Ub conjugate requires dimerization of the TRIM5 alpha RING domain. Our data explain how higher-order oligomerization of TRIM5 alpha, which is promoted by the interaction with the retroviral capsid, enhances the E3 Ub ligase activity of TRIM5 alpha and contributes to its antiretroviral function. This E3 mechanism, in which RING dimerization is transient and depends on the interaction of the TRIM protein with the ligand, is likely to be conserved in many members of the TRIM family and may have evolved to facilitate recognition of repetitive epitope patterns associated with infection. C1 [Yudina, Zinaida; Johnson, Rory; Biris, Nikolaos; Taylor, Alexander B.; Hart, P. John; Demeler, Borries; Ivanov, Dmitri N.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Roa, Amanda; Vieira, Daniel A. de Souza Aranha; Tsiperson, Vladislav; Reszka, Natalia; Diaz-Griffero, Felipe] Albert Einstein Coll Med, Microbiol & Immunol, Bronx, NY 10461 USA. RP Diaz-Griffero, F (reprint author), Albert Einstein Coll Med, Microbiol & Immunol, Bronx, NY 10461 USA. EM felipe.diaz-griffero@einstein.yu.edu; ivanov@uthscsa.edu FU Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH) [NIH P50 GM082545]; Robert A. Welch Foundation [AQ-1399]; NIH [R01 AI087390, R21 AI102824, R56 AI108432, R01 AI104476, P30 CA054174]; Cancer Prevention and Research Institute of Texas (CPRIT); NIH-NIGMS [P41 GM103403]; NIH-ORIP HEI at Argonne National Laboratory under DOE Office of Science [S10 RR029205, DE-AC02-06CH11357] FX This research was supported in part by the Collaborative Development Award to D.N.I. from the Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH; NIH P50 GM082545); R01 AI087390, R21 AI102824, and R56 AI108432 to F.D.-G; Robert A. Welch Foundation grant AQ-1399 to P.J.H; NIH R01 AI104476 to D.N.I.; and Scholar Award from the Cancer Prevention and Research Institute of Texas (CPRIT) to D.N.I. A.R., D.A.d.S.A.V., V.T., N.R., and F.D.-G. were supported by NIH grants R01 AI087390, R21 AI102824, and R56 AI108432 to F.D.-G. The NMR, X-ray, and Analytical Ultracentrifugation core facilities at the UT Health Science Center at San Antonio (UTHSCSA) are supported in part by the NIH P30 CA054174 to the Cancer Therapy and Research Center. B.D. acknowledges support from NSF for the development of the UltraScan Science Gateway used in the analysis of AUC data (ACI-1339649 and TG-MCB070039). X-ray diffraction data were collected at the Advanced Photon Source beamline 24-IDC NE-CAT funded by NIH-NIGMS P41 GM103403 and NIH-ORIP HEI S10 RR029205 at Argonne National Laboratory under DOE Office of Science contract no. DE-AC02-06CH11357. NR 50 TC 10 Z9 10 U1 0 U2 6 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 AUG 4 PY 2015 VL 12 IS 5 BP 788 EP 797 DI 10.1016/j.celrep.2015.06.072 PG 10 WC Cell Biology SC Cell Biology GA CO2PT UT WOS:000358999800008 PM 26212332 ER PT J AU Fischer, M DeCaprio, JA AF Fischer, Martin DeCaprio, James A. TI Does Arabidopsis thaliana DREAM of cell cycle control? SO EMBO JOURNAL LA English DT Editorial Material ID GENE-EXPRESSION; COMPLEX; MYB AB Strict temporal control of cell cycle gene expression is essential for all eukaryotes including animals and plants. DREAM complexes have been identified in worm, fly, and mammals, linking several distinct transcription factors to coordinate gene expression throughout the cell cycle. In this issue of The EMBO Journal, Kobayashi et al (2015) identify distinct activator and repressor complexes for genes expressed during the G2 and M phases in Arabidopsis that can be temporarily separated during proliferating and post-mitotic stages of development. The complexes incorporate specific activator and repressor MYB and E2F transcription factors and indicate the possibility of the existence of multiple DREAM complexes in plants. C1 [Fischer, Martin; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fischer, Martin; DeCaprio, James A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fischer, Martin; DeCaprio, James A.] Harvard Univ, Sch Med, Boston, MA USA. RP Fischer, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu RI Fischer, Martin/I-4825-2014 OI Fischer, Martin/0000-0002-3429-1876 FU NCI NIH HHS [R01 CA063113] NR 10 TC 1 Z9 2 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD AUG 4 PY 2015 VL 34 IS 15 BP 1987 EP 1989 DI 10.15252/embj.201592196 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CO1XY UT WOS:000358950800001 PM 26089020 ER PT J AU Kearney, DJ Simpson, TL AF Kearney, David J. Simpson, Tracy L. TI Broadening the Approach to Posttraumatic Stress Disorder and the Consequences of Trauma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID QUALITY-OF-LIFE; PTSD TREATMENT; THERAPY; TRIAL; VETERANS; EXPOSURE C1 [Kearney, David J.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Kearney, David J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Kearney, DJ (reprint author), Seattle VAMC 111GI, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM david.kearney@va.gov NR 20 TC 0 Z9 0 U1 1 U2 7 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 AUG 4 PY 2015 VL 314 IS 5 BP 453 EP 455 DI 10.1001/jama.2015.7522 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CO1OI UT WOS:000358924500009 PM 26241596 ER PT J AU Rhodes, KV Rodgers, M Sommers, M Hanlon, A Chittams, J Doyle, A Datner, E Crits-Christoph, P AF Rhodes, Karin V. Rodgers, Melissa Sommers, Marilyn Hanlon, Alexandra Chittams, Jesse Doyle, Andrea Datner, Elizabeth Crits-Christoph, Paul TI Brief Motivational Intervention for Intimate Partner Violence and Heavy Drinking in the Emergency Department A Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ALCOHOL-USE; DOMESTIC VIOLENCE; AGGRESSION; SYMPTOMS; INJURY; AUDIT; RISK AB IMPORTANCE Intimate partner violence (IPV) and heavy drinking are co-occurring public health problems, but integrated brief interventions for these conditions have not been tested. OBJECTIVE To determine whether a brief motivational intervention provided at the time of an emergency department (ED) visit reduces IPV and heavy drinking. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial conducted at 2 US academic urban EDs between January 2011 and December 2014 to assess the effectiveness of a motivational intervention for IPV-involved female ED patients (ages: 18-64 years; N = 600) who exceeded sex-specific safe drinking limits. All received social service referrals; 2: 2: 1 to brief intervention (n = 242), assessed control (n = 237), or no-contact control (n = 121). INTERVENTIONS A 20- to 30-minute manual-guided motivational intervention (recorded and monitored for fidelity) delivered by master's-level therapists with a follow-up telephone booster. The assessed control group received the same number of assessments as the brief intervention group; the no-contact control group was assessed only once at 3 months. MAIN OUTCOMES AND MEASURES Incidents of heavy drinking and experiencing IPV measured over prespecified, 12 weekly assessments using an interactive voice response system. RESULTS Of 600 participants, 80% were black women with a mean age of 32 years. Retention was 89% for 2 or more interactive voice response system calls. Seventy-eight percent of women completed the 3-month interview, 79% at 6 months, and 71% at 12 months. During the 12-week period following the brief motivational intervention, there were no significant differences between the intervention group and the assessed control group on weekly assessments for experiencing IPV (odds ratio [OR], 1.02; 95% CI, 0.98-1.06) or heavy drinking (OR, 0.99; 95% CI, 0.96-1.03). From baseline to 12 weeks, the number of women with any IPV in the past week decreased from 57%(134 of 237) in the intervention group to 43%(83 of 194) and from 63%(145 of 231) in the assessed control group to 41%(77 of 187) (absolute difference of 8%). From baseline to 12 weeks, the number of women with past week heavy drinking decreased from 51%(120 of 236) in the intervention group to 43%(83 of 194) and from 46%(107 of 231) in the assessed control group to 41%(77 of 187) (absolute difference of 3%). At 12 months, 43%(71 of 165) of the intervention group and 47%(78 of 165) of the assessed control group reported no IPV during the previous 3 months and 19% (29 of 152) of the intervention group and 24%(37 of 153) of the control group had reduced their alcohol consumption to sex-specific National Institute on Alcohol Abuse and Alcoholism safe drinking levels. CONCLUSIONS AND RELEVANCE For women experiencing IPV and heavy drinking, the use of a brief motivational intervention in the ED compared with assessed and no-contact controls did not significantly reduce the days of heavy drinking or incidents of IPV. These findings do not support a brief motivational intervention in this setting. C1 [Rhodes, Karin V.; Rodgers, Melissa; Datner, Elizabeth; Crits-Christoph, Paul] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Rhodes, Karin V.; Doyle, Andrea] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Sommers, Marilyn; Hanlon, Alexandra; Chittams, Jesse] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Datner, Elizabeth] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Rhodes, KV (reprint author), Univ Penn, Ctr Emergency Care Policy & Res, Dept Emergency Med, Perelman Sch Med,HUP, 34th & Spruce St,First Floor Ravidin, Philadelphia, PA 19104 USA. EM karin.rhodes@uphs.upenn.edu FU National Institute on Alcohol Abuse and Alcoholism [R01-AA018705] FX This project was funded by award R01-AA018705 from the National Institute on Alcohol Abuse and Alcoholism. NR 40 TC 5 Z9 5 U1 1 U2 8 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 AUG 4 PY 2015 VL 314 IS 5 BP 466 EP 477 DI 10.1001/jama.2015.8369 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CO1OI UT WOS:000358924500011 PM 26241598 ER PT J AU Steenkamp, MM Litz, BT Hoge, CW Marmar, CR AF Steenkamp, Maria M. Litz, Brett T. Hoge, Charles W. Marmar, Charles R. TI Psychotherapy for Military-Related PTSD A Review of Randomized Clinical Trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; EYE-MOVEMENT DESENSITIZATION; COGNITIVE PROCESSING THERAPY; REALITY EXPOSURE THERAPY; VIETNAM COMBAT VETERANS; WAR VETERANS; HEALTH-CARE; BEHAVIORAL THERAPY; SELF-MANAGEMENT; SYMPTOMS AB IMPORTANCE Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder common among military personnel and veterans. First-line psychotherapies most often recommended for PTSD consist mainly of "trauma-focused" psychotherapies that involve focusing on details of the trauma or associated cognitive and emotional effects. OBJECTIVE To examine the effectiveness of psychotherapies for PTSD in military and veteran populations. EVIDENCE REVIEW PubMed, PsycINFO, and PILOTS were searched for randomized clinical trials (RCTs) of individual and group psychotherapies for PTSD in military personnel and veterans, published from January 1980 to March 1, 2015. We also searched reference lists of articles, selected reviews, and meta-analyses. Of 891 publications initially identified, 36 were included. FINDINGS Two trauma-focused therapies, cognitive processing therapy (CPT) and prolonged exposure, have been the most frequently studied psychotherapies for military-related PTSD. Five RCTs of CPT (that included 481 patients) and 4 RCTs of prolonged exposure (that included 402 patients) met inclusion criteria. Focusing on intent-to-treat outcomes, within-group posttreatment effect sizes for CPT and prolonged exposure were large (Cohen d range, 0.78-1.10). CPT and prolonged exposure also outperformed waitlist and treatment-as-usual control conditions. Forty-nine percent to 70% of participants receiving CPT and prolonged exposure attained clinically meaningful symptom improvement (defined as a 10- to 12-point decrease in interviewer-assessed or self-reported symptoms). However, mean posttreatment scores for CPT and prolonged exposure remained at or above clinical criteria for PTSD, and approximately two-thirds of patients receiving CPT or prolonged exposure retained their PTSD diagnosis after treatment (range, 60%-72%). CPT and prolonged exposure were marginally superior compared with non-trauma-focused psychotherapy comparison conditions. CONCLUSIONS AND RELEVANCE In military and veteran populations, trials of the first-line trauma-focused interventions CPT and prolonged exposure have shown clinically meaningful improvements for many patients with PTSD. However, nonresponse rates have been high, many patients continue to have symptoms, and trauma-focused interventions show marginally superior results compared with active control conditions. There is a need for improvement in existing PTSD treatments and for development and testing of novel evidence-based treatments, both trauma-focused and non-trauma-focused. C1 [Steenkamp, Maria M.; Marmar, Charles R.] NYU, Langone Sch Med, Steven & Alexandra Cohen Vet Ctr Posttraumat Stre, New York, NY 10016 USA. [Litz, Brett T.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA 02118 USA. [Hoge, Charles W.] Walter Reed Army Inst Res, Silver Spring, MD USA. RP Steenkamp, MM (reprint author), NYU, Langone Sch Med, Steven & Alexandra Cohen Vet Ctr Posttraumat Stre, One Pk Ave,Room 8-107, New York, NY 10016 USA. EM maria.steenkamp@nyumc.org NR 80 TC 42 Z9 42 U1 4 U2 39 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 AUG 4 PY 2015 VL 314 IS 5 BP 489 EP 500 DI 10.1001/jama.2015.8370 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CO1OI UT WOS:000358924500013 PM 26241600 ER PT J AU Spoont, MR Williams, JW Kehle-Forbes, S Nieuwsma, JA Mann-Wrobel, MC Gross, R AF Spoont, Michele R. Williams, John W., Jr. Kehle-Forbes, Shannon Nieuwsma, Jason A. Mann-Wrobel, Monica C. Gross, Raz TI Does This Patient Have Posttraumatic Stress Disorder? Rational Clinical Examination Systematic Review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID NATIONAL COMORBIDITY SURVEY; PRIMARY-CARE PATIENTS; DSM-IV DISORDERS; PTSD CHECKLIST; MENTAL-HEALTH; SCREENING INSTRUMENT; PROLONGED EXPOSURE; PERFORMANCE-CHARACTERISTICS; OPERATING CHARACTERISTICS; DIAGNOSTIC-ACCURACY AB IMPORTANCE Posttraumatic stress disorder (PTSD) is a relatively common mental health condition frequently seen, though often unrecognized, in primary care settings. Identifying and treating PTSD can greatly improve patient health and well-being. OBJECTIVE To systematically review the utility of self-report screening instruments for PTSD among primary care and high-risk populations. EVIDENCE REVIEW We searched MEDLINE and the National Center for PTSD's Published International Literature on Traumatic Stress (PILOTS) databases for articles published on screening instruments for PTSD published from January 1981 through March 2015. Study quality was rated using Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. STUDY SELECTION Studies of screening instruments for PTSD evaluated using gold standard structured clinical diagnostic interviews that had interview samples of at least 50 individuals. FINDINGS We identified 2522 citations, retrieved 318 for further review, and retained 23 cohort studies that evaluated 15 screening instruments for PTSD. Of the 23 studies, 15 were conducted in primary care settings in the United States (n = 14 707 were screened, n = 5374 given diagnostic interview, n = 814 had PTSD) and 8 were conducted in community settings following probable trauma exposure (ie, natural disaster, terrorism, and military deployment; n = 5302 were screened, n = 4263 given diagnostic interview, n = 393 were known to have PTSD with an additional 50 inferred by rates reported by authors). Two screens, the Primary Care PTSD Screen (PC-PTSD) and the PTSD Checklist were the best performing instruments. The 4-item PC-PTSD has a positive likelihood ratio of 6.9 (95% CI, 5.5-8.8) and a negative likelihood ratio of 0.30 (95% CI, 0.21-0.44) using the same score indicating a positive screen as used by the Department of Veterans Affairs in all of its primary care clinics. The 17-item PTSD Checklist has a positive likelihood ratio of 5.2 (95% CI, 3.6-7.5) and a negative likelihood ratio of 0.33 (95% CI, 0.29-0.37) using scores of around 40 as indicating a positive screen. Using the same score employed by primary care clinics in the Department of Veterans Affairs to indicate a positive screen, the 4-item PC-PTSD has a sensitivity of 0.69 (95% CI, 0.55-0.81), a specificity of 0.92 (95% CI, 0.86-0.95), a positive likelihood ratio of 8.49 (95% CI, 5.56-12.96) and a negative likelihood ratio of 0.34 (95% CI, 0.22-0.48). For the 17-item PTSD Checklist, scores around 40 as indicating a positive screen, have a sensitivity of 0.70 (95% CI, 0.64-0.77), a specificity of 0.90 (95% CI, 0.84-0.93), a positive likelihood ratio of 6.8 (95% CI, 4.7-9.9) and a negative likelihood ratio of 0.33 (95% CI, 0.27-0.40). CONCLUSIONS AND RELEVANCE Two screening instruments, the PC-PTSD and the PTSD Checklist, show reasonable performance characteristics for use in primary care clinics or in community settings with high-risk populations. Both are easy to administer and interpret and can readily be incorporated into a busy practice setting. C1 [Spoont, Michele R.] US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Minneapolis Vet Affairs Healthcare Syst, Minneapolis, MN USA. [Spoont, Michele R.; Kehle-Forbes, Shannon] Minneapolis Vet Affairs Healthcare Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Spoont, Michele R.; Kehle-Forbes, Shannon] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Williams, John W., Jr.] Durham Vet Affairs Med Ctr, US Dept Vet Affairs Evidence Based Synth Ctr, Durham, NC USA. [Williams, John W., Jr.] Duke Univ, Sch Med, Div Gen Internal Med, Durham, NC USA. [Nieuwsma, Jason A.] Durham Vet Affairs Med Ctr, Midatlantic Mental Illness Res Educ & Clin Ctr, Durham, NC USA. [Nieuwsma, Jason A.; Mann-Wrobel, Monica C.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Mann-Wrobel, Monica C.] Durham Vet Affairs Med Ctr, Dept Mental Hlth, Durham, NC USA. [Gross, Raz] Tel Aviv Univ, Dept Epidemiol & Prevent Med, Sch Publ Hlth, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Gross, Raz] Chaim Sheba Med Ctr, Gertner Inst Hlth Policy & Epidemiol, IL-52621 Tel Hashomer, Israel. RP Spoont, MR (reprint author), Minneapolis Vet Affairs Healthcare Syst, Ctr Chron Dis Outcomes Res, 152,Bldg 9,1 Vet Dr, Minneapolis, MN 55417 USA. EM michele.spoont@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative (VA-ESP) [09-009, 09-010] FX This report is based on research conducted by the Evidence-based Synthesis Program (ESP) Center located at the Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota, and expanded on by the ESP Center located at the Durham Veterans Affairs Medical Center, Durham, North Carolina. Both centers are funded by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative (VA-ESP Project #09-009 and VA-ESP Project #09-010, respectively). The initial evidence report is available at http://www.hsrd.research.va.gov/publications/esp/ptsd-screening.cfm. NR 85 TC 10 Z9 10 U1 4 U2 17 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 AUG 4 PY 2015 VL 314 IS 5 BP 501 EP 510 DI 10.1001/jama.2015.7877 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CO1OI UT WOS:000358924500014 PM 26241601 ER PT J AU Alawieh, A Sabra, M Sabra, Z Tomlinson, S Zaraket, FA AF Alawieh, Ali Sabra, Mohammed Sabra, Zahraa Tomlinson, Stephen Zaraket, Fadi A. TI Molecular Architecture of Spinal Cord Injury Protein Interaction Network SO PLOS ONE LA English DT Article ID FUNCTIONAL RECOVERY; PROTEOMIC ANALYSIS; DATABASE; ORGANIZATION; INFLAMMATION; PERMEABILITY; MECHANISMS; NEUROTROPHIN-3; DEGENERATION; APOPTOSIS AB Spinal cord injury (SCI) is associated with complex pathophysiological processes that follow the primary traumatic event and determine the extent of secondary damage and functional recovery. Numerous reports have used global and hypothesis-driven approaches to identify protein changes that contribute to the overall pathology of SCI in an effort to identify potential therapeutic interventions. In this study, we use a semi-automatic annotation approach to detect terms referring to genes or proteins dysregulated in the SCI literature and develop a curated SCI interactome. Network analysis of the SCI interactome revealed the presence of a rich-club organization corresponding to a "powerhouse" of highly interacting hub-proteins. Studying the modular organization of the network have shown that rich-club proteins cluster into modules that are specifically enriched for biological processes that fall under the categories of cell death, inflammation, injury recognition and systems development. Pathway analysis of the interactome and the rich-club revealed high similarity indicating the role of the rich-club proteins as hubs of the most prominent pathways in disease pathophysiology and illustrating the centrality of pro-and anti-survival signal competition in the pathology of SCI. In addition, evaluation of centrality measures of single nodes within the rich-club have revealed that neuronal growth factor (NGF), caspase 3, and H-Ras are the most central nodes and potentially an interesting targets for therapy. Our integrative approach uncovers the molecular architecture of SCI interactome, and provide an essential resource for evaluating significant therapeutic candidates. C1 [Alawieh, Ali; Sabra, Zahraa; Tomlinson, Stephen] Med Univ S Carolina, Dept Neurosci, Inst Neurosci, Charleston, SC 29425 USA. [Alawieh, Ali; Sabra, Mohammed; Sabra, Zahraa; Zaraket, Fadi A.] Amer Univ Beirut, Dept Elect & Comp Engn, Beirut, Lebanon. [Tomlinson, Stephen] Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Neurosci, Inst Neurosci, Charleston, SC 29425 USA. EM tomlinss@musc.edu; fz11@aub.edu.lb OI Alawieh, Ali/0000-0003-2601-8850 FU Veterans Affairs merit awards [BX001218, RX001141]; Farouk Jabre Award [2013/14] FX This work was supported by Veterans Affairs merit awards [BX001218 and RX001141] to S.T. and the Farouk Jabre Award [2013/14] to F.Z. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 0 Z9 0 U1 0 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 AUG 4 PY 2015 VL 10 IS 8 AR e0135024 DI 10.1371/journal.pone.0135024 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO1VB UT WOS:000358942700090 PM 26241741 ER PT J AU Duvvuri, U AF Duvvuri, Umamaheswar TI ANO1 plays a critical role in prostatic hyperplasia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID CANCER PROGRESSION; CHANNEL ANO1; TMEM16A; PROTEIN; EXPRESSION; 11Q13; GENE; HEAD; EGFR C1 [Duvvuri, Umamaheswar] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Duvvuri, Umamaheswar] Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA 15240 USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15213 USA. EM duvvuriu@upmc.edu NR 17 TC 0 Z9 0 U1 0 U2 3 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 AUG 4 PY 2015 VL 112 IS 31 BP 9506 EP 9507 DI 10.1073/pnas.1512075112 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO1QQ UT WOS:000358930600035 PM 26216998 ER PT J AU Zhang, XL Tian, YL Zhang, C Tian, XY Ross, AW Moir, RD Sun, HB Tanzi, RE Moore, A Ran, CZ AF Zhang, Xueli Tian, Yanli Zhang, Can Tian, Xiaoyu Ross, Alana W. Moir, Robert D. Sun, Hongbin Tanzi, Rudolph E. Moore, Anna Ran, Chongzhao TI Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer's disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Alzheimer's; amyloid; imaging; fluorescence; curcumin ID AD MOUSE MODELS; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO DETECTION; REVERSE DEFICITS; TRANSGENIC MICE; SYNAPTIC PLASTICITY; FIBRILLAR OLIGOMERS; DETECTION FAILURE; DRUG DEVELOPMENT; MEMORY DEFICITS AB Near-infrared fluorescence (NIRF) molecular imaging has been widely applied to monitoring therapy of cancer and other diseases in preclinical studies; however, this technology has not been applied successfully to monitoring therapy for Alzheimer's disease (AD). Although several NIRF probes for detecting amyloid beta (A beta) species of AD have been reported, none of these probes has been used to monitor changes of A beta s during therapy. In this article, we demonstrated that CRANAD-3, a curcumin analog, is capable of detecting both soluble and insoluble A beta species. In vivo imaging showed that the NIRF signal of CRANAD-3 from 4-mo-old transgenic AD (APP/PS1) mice was 2.29-fold higher than that from age-matched wild-type mice, indicating that CRANAD-3 is capable of detecting early molecular pathology. To verify the feasibility of CRANAD-3 for monitoring therapy, we first used the fast A beta-lowering drug LY2811376, a well-characterized beta-amyloid cleaving enzyme-1 inhibitor, to treat APP/PS1 mice. Imaging data suggested that CRANAD-3 could monitor the decrease in A beta s after drug treatment. To validate the imaging capacity of CRANAD-3 further, we used it to monitor the therapeutic effect of CRANAD-17, a curcumin analog for inhibition of A beta cross-linking. The imaging data indicated that the fluorescence signal in the CRANAD-17-treated group was significantly lower than that in the control group, and the result correlated with ELISA analysis of brain extraction and A beta plaque counting. It was the first time, to our knowledge, that NIRF was used to monitor AD therapy, and we believe that our imaging technology has the potential to have a high impact on AD drug development. C1 [Zhang, Xueli; Tian, Yanli; Ross, Alana W.; Moore, Anna; Ran, Chongzhao] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Mol Imaging Lab,Sch Med,MIT,Dept Radiol, Charlestown, MA 02129 USA. [Zhang, Xueli; Sun, Hongbin] China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China. [Zhang, Xueli] Southeast Univ, ZhongDa Hosp, Dept Pharm, Nanjing 210009, Jiangsu, Peoples R China. [Tian, Yanli] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510080, Guangdong, Peoples R China. [Zhang, Can; Moir, Robert D.; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. [Tian, Xiaoyu] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA. RP Moore, A (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Mol Imaging Lab,Sch Med,MIT,Dept Radiol, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu; cran@nmr.mgh.harvard.edu FU NIH [K25AG036760] FX We thank Pamela Pantazopoulos for proofreading the manuscript. This work was supported by Award K25AG036760 from NIH (to C.R.). NR 84 TC 19 Z9 19 U1 16 U2 85 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 AUG 4 PY 2015 VL 112 IS 31 BP 9734 EP 9739 DI 10.1073/pnas.1505420112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO1QQ UT WOS:000358930600074 PM 26199414 ER PT J AU Kuoa, SY Castoreno, AB Aldrich, LN Lassen, KG Goel, G Dancik, V Kuballa, P Latorre, I Conway, KL Sarkar, S Maetzel, D Jaenisch, R Clemons, PA Schreiber, SL Shamji, AF Xavier, RJ AF Kuoa, Szu-Yu Castoreno, Adam B. Aldrich, Leslie N. Lassen, Kara G. Goel, Gautam Dancik, Vlado Kuballa, Petric Latorre, Isabel Conway, Kara L. Sarkar, Sovan Maetzel, Dorothea Jaenisch, Rudolf Clemons, Paul A. Schreiber, Stuart L. Shamji, Alykhan F. Xavier, Ramnik J. TI Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE high-throughput screening; autophagy; small-molecule probes; Crohn's disease ID IMPAIRED AUTOPHAGY; BUILD/COUPLE/PAIR STRATEGY; SELECTIVE AUTOPHAGY; ATG16L1; CELLS; LC3; NEURODEGENERATION; DYSFUNCTION; INHIBITORS; MUTATIONS AB Studies of human genetics and pathophysiology have implicated the regulation of autophagy in inflammation, neurodegeneration, infection, and autoimmunity. These findings have motivated the use of small-molecule probes to study how modulation of autophagy affects disease-associated phenotypes. Here, we describe the discovery of the small-molecule probe BRD5631 that is derived from diversity-oriented synthesis and enhances autophagy through an mTOR-independent pathway. We demonstrate that BRD5631 affects several cellular disease phenotypes previously linked to autophagy, including protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in the context of cellular homeostasis and disease. C1 [Kuoa, Szu-Yu; Castoreno, Adam B.; Aldrich, Leslie N.; Dancik, Vlado; Latorre, Isabel; Clemons, Paul A.; Schreiber, Stuart L.; Shamji, Alykhan F.] Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. [Kuoa, Szu-Yu] Harvard Univ, Dept Cellular & Mol Biol, Cambridge, MA 02138 USA. [Aldrich, Leslie N.; Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Lassen, Kara G.; Goel, Gautam; Kuballa, Petric; Conway, Kara L.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Lassen, Kara G.; Goel, Gautam; Kuballa, Petric; Conway, Kara L.; Xavier, Ramnik J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Goel, Gautam; Kuballa, Petric; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Sarkar, Sovan; Maetzel, Dorothea] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Sarkar, Sovan] Univ Birmingham, Coll Med & Dent Sci, Inst Biomed Res, Birmingham B15 2TT, W Midlands, England. [Jaenisch, Rudolf] Skolkovo Inst Sci & Technol Skoltech, Skolkovo 143025, Moscow Region, Russia. [Schreiber, Stuart L.] Howard Hughes Med Inst, Cambridge, MA 02142 USA. RP Schreiber, SL (reprint author), Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. EM stuart_schreiber@harvard.edu; ashamji@broadinstitute.org; xavier@molbio.mgh.harvard.edu OI Latorre, Isabel/0000-0003-0638-1783 FU Leona M. and Harry B. Helmsley Charitable Trust Grant [500203]; National Institute of Allergy and Infectious Diseases' Center for Excellence in Translational Research Grant [U19AI109725]; Birmingham Fellowship; National Niemann-Pick Disease Foundation Foundation; Skoltech Center; NIH [DK097485, U01CA176152, R01-NS088538, MH104610] FX We are grateful to David Rubinsztein for providing the eGFP-HDQ74 construct, and to Noboru Mizushima for providing the Atg5+/+ and Atg5-/- MEFs. We thank the Compound Management Team for providing compound plates and synthetic intermediates, and the members of the R.J.X. and S.L.S. laboratories for insightful discussions. Research reported in this publication was supported by the Leona M. and Harry B. Helmsley Charitable Trust Grant 500203 (to S.L.S. and R.J.X.); the National Institute of Allergy and Infectious Diseases' Center for Excellence in Translational Research Grant U19AI109725 (to S.L.S., A.F.S., and R.J.X.); Birmingham Fellowship (S.S.); the National Niemann-Pick Disease Foundation Foundation (D.M.), Skoltech Center (R.J.); and NIH Grants DK097485 (to R.J.X.), U01CA176152 (to S.L.S.), R01-NS088538 (to R.J.), and MH104610 (to R.J.). S.L.S. is an Investigator of the Howard Hughes Medical Institute. NR 48 TC 2 Z9 2 U1 3 U2 15 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 AUG 4 PY 2015 VL 112 IS 31 BP E4281 EP E4287 DI 10.1073/pnas.1512289112 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO1QQ UT WOS:000358930600019 ER PT J AU Lahava, A AF Lahava, Amir TI Reply to El-Dib and Glass: Neuroplasticity in the auditory cortex in premature newborns exposed to recorded maternal sounds SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID INFANTS C1 [Lahava, Amir] Harvard Univ, Sch Med, MassGen Hosp Children, Dept Pediat, Boston, MA 02114 USA. [Lahava, Amir] Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI 02905 USA. RP Lahava, A (reprint author), Harvard Univ, Sch Med, MassGen Hosp Children, Dept Pediat, Boston, MA 02114 USA. EM amir@hms.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 1 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 AUG 4 PY 2015 VL 112 IS 31 BP E4167 EP E4167 DI 10.1073/pnas.1509728112 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO1QQ UT WOS:000358930600006 PM 26170334 ER PT J AU Sunwoo, H Wua, JY Lee, JT AF Sunwoo, Hongjae Wua, John Y. Lee, Jeannie T. TI The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE super resolution microscopy; Xist RNA; Polycomb; X inactivation; chromosome ID INACTIVE X-CHROMOSOME; OPTICAL RECONSTRUCTION MICROSCOPY; FACULTATIVE HETEROCHROMATIN; SUPERRESOLUTION MICROSCOPY; RNA; GENE; LOCALIZATION; METHYLATION; PROTEINS; BINDING AB X-chromosome inactivation (XCI) is initiated by the long noncoding RNA Xist, which coats the inactive X (Xi) and targets Polycomb repressive complex 2 (PRC2) in cis. Epigenomic analyses have provided significant insight into Xist binding patterns and chromatin organization of the Xi. However, such epigenomic analyses are limited by averaging of population-wide dynamics and do not inform behavior of single cells. Here we view Xist RNA and the Xi at 20-nm resolution using STochastic Optical Reconstruction Microscopy (STORM) in mouse cells. We observe dynamics at the single-cell level not predicted by epigenomic analysis. Only similar to 50 hubs of Xist RNA occur on the Xi in the maintenance phase, corresponding to 50-100 Xist molecules per Xi and contrasting with the chromosome-wide "coat" observed by deep sequencing and conventional microscopy. Likewise, only similar to 50 hubs PRC2 are observed. PRC2 and Xist foci are not randomly distributed but showed statistically significant spatial association. Knock-off experiments enable visualization of the dynamics of dissociation and relocalization onto the Xi and support a functional tethering of Xist and PRC2. Our analysis reveals that Xist-PRC2 complexes are less numerous than expected and suggests methylation of nucleosomes in a hit-and-run model. C1 [Sunwoo, Hongjae; Wua, John Y.; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Sunwoo, Hongjae; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Med, Boston, MA 02114 USA. [Sunwoo, Hongjae; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Wua, John Y.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Wua, John Y.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU MGH Fund for Medical Discovery; National Science Foundation; NIH [RO1-GM090278] FX We thank Dr. Xiaowei Zhuang for critical comments on the manuscript and many helpful discussions regarding STORM. We also thank members of the Lee laboratory for support and valuable discussions; D. Spector (Cold Spring Harbor Laboratory) for the 2-6-3 cell line; Benjamin Heuberger (Massachusetts General Hospital) for oligo synthesis; Do-hyun Kim (Food and Drug Administration), Christopher E. Carr (MGH), Hongshin Sunwoo, and Doory Kim (Zhuang laboratory) for help with MatLab programming. H.S. was supported by the MGH Fund for Medical Discovery. J.Y.W. was supported by National Science Foundation Graduate Research fellowship. J.T.L. was supported by NIH RO1-GM090278. J.T.L. is an Investigator of the Howard Hughes Medical Institute. NR 39 TC 14 Z9 14 U1 1 U2 6 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 AUG 4 PY 2015 VL 112 IS 31 BP E4216 EP E4225 DI 10.1073/pnas.1503690112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO1QQ UT WOS:000358930600012 PM 26195790 ER PT J AU Rochau, U Sroczynski, G Wolf, D Schmidt, S Jahn, B Kluibenschaedl, M Conrads-Frank, A Stenehjem, D Brixner, D Radich, J Gastl, G Siebert, U AF Rochau, Ursula Sroczynski, Gaby Wolf, Dominik Schmidt, Stefan Jahn, Beate Kluibenschaedl, Martina Conrads-Frank, Annette Stenehjem, David Brixner, Diana Radich, Jerald Gastl, Guenther Siebert, Uwe TI Cost-effectiveness of the sequential application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article DE Chronic myeloid leukemia; decision-analytic model; tyrosine kinase inhibitors; decision analysis; cost-effectiveness analysis; health economic modeling ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; CANCER DRUGS; IMATINIB-RESISTANT; 1ST-LINE TREATMENT; DECISION-ANALYSIS; INTERFERON-ALPHA; FOLLOW-UP; BCR-ABL; PHASE AB Several tyrosine kinase inhibitors (TKIs) are approved for chronic myeloid leukemia (CML) therapy. We evaluated the long-term cost-effectiveness of seven sequential therapy regimens for CML in Austria. A cost-effectiveness analysis was performed using a state-transition Markov model. As model parameters, we used published trial data, clinical, epidemiological and economic data from the Austrian CML registry and national databases. We performed a cohort simulation over a life-long time-horizon from a societal perspective. Nilotinib without second-line TKI yielded an incremental cost-utility ratio of 121 400 Euro/quality-adjusted life year (QALY) compared to imatinib without second-line TKI after imatinib failure. Imatinib followed by nilotinib after failure resulted in 131 100 Euro/QALY compared to nilotinib without second-line TKI. Nilotinib followed by dasatinib yielded 152 400 Euro/QALY compared to imatinib followed by nilotinib after failure. Remaining strategies were dominated. The sequential application of TKIs is standard-of-care, and thus, our analysis points toward imatinib followed by nilotinib as the most cost-effective strategy. C1 [Rochau, Ursula; Sroczynski, Gaby; Jahn, Beate; Kluibenschaedl, Martina; Conrads-Frank, Annette; Brixner, Diana; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth & Hlth Technol Assessment, Inst Publ Hlth Med Decis Making & Hlth Technol As, Hall In Tirol, Austria. [Rochau, Ursula; Brixner, Diana; Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Area Hlth Technol Assessment & Bioinformat 4, Innrain 66a, A-6020 Innsbruck, Austria. [Wolf, Dominik; Schmidt, Stefan; Gastl, Guenther] Med Univ Innsbruck, Hematol & Oncol, Internal Med 5, A-6020 Innsbruck, Austria. [Wolf, Dominik] Univ Clin Bonn UKB, Oncol Hematol & Rheumatol, Med Clin 3, Bonn, Germany. [Stenehjem, David; Brixner, Diana] Univ Utah, Dept Pharmacotherapy, Salt Lake City, UT USA. [Stenehjem, David; Brixner, Diana] Univ Utah, Program Personalized Hlth Care, Salt Lake City, UT USA. [Stenehjem, David] Univ Utah, Hosp & Clin, Huntsman Canc Inst, Salt Lake City, UT USA. [Radich, Jerald] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Siebert, U (reprint author), ONCOTYROL Ctr Personalized Canc Med, Area Hlth Technol Assessment & Bioinformat 4, Innrain 66a, A-6020 Innsbruck, Austria. EM uwe.siebert@oncotyrol.at NR 76 TC 0 Z9 0 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG 3 PY 2015 VL 56 IS 8 BP 2315 EP 2325 DI 10.3109/10428194.2014.982635 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA DD2GW UT WOS:000369741700015 PM 25393806 ER PT J AU Pierce, RH Campbell, JS Pai, SI Brody, JD Kohrt, HEK AF Pierce, Robert H. Campbell, Jean S. Pai, Sara I. Brody, Joshua D. Kohrt, Holbrook E. K. TI In-situ tumor vaccination: Bringing the fight to the tumor SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article; Proceedings Paper CT DNA Vaccine 2014 Conference CY JUL 21-23, 2014 CL San Diego, CA DE adaptive resistance; intratumoral; immunotherapy; melanoma ID CD8(+) T-CELLS; IFN-GAMMA PRODUCTION; HPV-ASSOCIATED HEAD; INTRATUMORAL INJECTION; CANCER-IMMUNOTHERAPY; ANTITUMOR IMMUNITY; PD-1 BLOCKADE; LUNG-CANCER; IMMUNOREGULATORY FUNCTIONS; ANTICANCER CHEMOTHERAPY AB After decades of development in the shadow of traditional cancer treatment, immunotherapy has come into the spotlight. Treatment of metastatic tumors with monoclonal antibodies to T cell checkpoints like programed cell death 1 (PD-1) or its ligand, (PD-L1), have resulted in significant clinical responses across multiple tumor types. However, these therapies fail in the majority of patients with solid tumors, in particular those who lack PD1(+)CD8(+) tumor-infiltrating lymphocytes within their tumors. Intratumoral in situ vaccination approaches seek to enhance immunogenicity, generate tumor infiltrating lymophcytes (TIL) and drive a systemic anti-tumor immune response, directed against unvaccinated, disseminated tumors. Given the emerging picture of intratumoral immunotherapy as safe and capable of delivering systemic efficacy, it is anticipated that these approaches will become integrated into future multi-modality therapy. C1 [Pierce, Robert H.; Campbell, Jean S.] OncoSec Med Inc, San Diego, CA USA. [Pai, Sara I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Brody, Joshua D.] Icahn Sch Med Mt Sinai, Div Hematol Oncol, Hess Ctr Sci & Med, New York, NY 10029 USA. [Kohrt, Holbrook E. K.] Stanford Univ, Ctr Clin Sci Res, Div Hematol, Stanford, CA 94305 USA. [Kohrt, Holbrook E. K.] Stanford Univ, Ctr Clin Sci Res, Div Oncol, Stanford, CA 94305 USA. RP Kohrt, HEK (reprint author), Stanford Univ, Ctr Clin Sci Res, Div Hematol, Stanford, CA 94305 USA. EM kohrt@stanford.edu FU NIDCR NIH HHS [R01 DE025340] NR 88 TC 6 Z9 6 U1 3 U2 18 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD AUG 3 PY 2015 VL 11 IS 8 BP 1901 EP 1909 DI 10.1080/21645515.2015.1049779 PG 9 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA CP1AQ UT WOS:000359608600013 PM 26055074 ER PT J AU Gremmel, T Frelinger, AL Michelson, AD AF Gremmel, Thomas Frelinger, Andrew L., III Michelson, Alan D. TI Soluble CD40 Ligand in Aspirin-Treated Patients Undergoing Cardiac Catheterization SO PLOS ONE LA English DT Article ID CORONARY-ARTERY-DISEASE; ELEVATION MYOCARDIAL-INFARCTION; LOW-DOSE ASPIRIN; CARDIOVASCULAR-DISEASE; PLATELET ACTIVATION; PLASMA-LEVELS; P-SELECTIN; CLOPIDOGREL; RISK; EVENTS AB Plasma soluble CD40 ligand (sCD40L) is mainly generated by cleavage of CD40L from the surface of activated platelets, and therefore considered a platelet activation marker. Although the predictive value of sCD40L for ischemic events has been demonstrated in patients with acute coronary syndromes (ACS), studies on the association of sCD40L with cardiovascular outcomes in lower risk populations yielded heterogeneous results. We therefore sought to investigate factors influencing sCD40L levels, and the predictive value of sCD40L for long-term ischemic events in unselected, aspirin-treated patients undergoing cardiac catheterization. sCD40L was determined by a commercially available enzyme-linked immunosorbent assay in 682 consecutive patients undergoing cardiac catheterization. Two-year follow-up data were obtained from 562 patients. Dual antiplatelet therapy with aspirin and clopidogrel was associated with significantly lower levels of sCD40L and lower platelet surface expressions of P-selectin and activated GPIIb/IIIa compared to aspirin monotherapy (all p <= 0.01). Hypertension was linked to lower plasma concentrations of sCD40L, whereas female sex, increasing high-sensitivity C-reactive protein, and hematocrit were associated with higher sCD40L concentrations (all p<0.05). sCD40L levels were similar in patients without and with the primary endpoint in the overall study population (p = 0.4). Likewise, sCD40L levels did not differ significantly between patients without and with the secondary endpoints (both p >= 0.4). Similar results were obtained when only patients with angiographically-proven coronary artery disease (n = 459), stent implantation (n = 205) or ACS (n = 125) were analyzed. The adjustment for differences in patient characteristics by multivariate regression analyses did not change the results. ROC curve analyses did not reveal cut-off values for sCD40L for the prediction of the primary or secondary endpoints. In conclusion, plasma sCD40L levels are reduced by antiplatelet therapy with clopidogrel, but not associated with long-term ischemic outcomes in unselected consecutive aspirin-treated patients undergoing cardiac catheterization. C1 [Gremmel, Thomas; Frelinger, Andrew L., III; Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Platelet Res Studies,Div Hematol Oncol,Boston, Boston, MA 02115 USA. [Gremmel, Thomas] Med Univ Vienna, Dept Internal Med 2, Vienna, Austria. RP Gremmel, T (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Platelet Res Studies,Div Hematol Oncol,Boston, 44 Binney St, Boston, MA 02115 USA. EM thomas.gremmel@childrens.harvard.edu OI Gremmel, Thomas/0000-0001-9554-7292 FU Bristol-Myers Squibb; GLSynthesis; Lilly/Daiichi Sankyo; Pfizer FX Alan D. Michelson has received grant support from Bristol-Myers Squibb, GLSynthesis, Lilly/Daiichi Sankyo and Pfizer, and served on data monitoring committees of Lilly/Daiichi Sankyo clinical trials. Andrew L. Frelinger has received grant support from Bristol-Myers Squibb, GLSynthesis, Lilly/Daiichi Sankyo and Pfizer. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. NR 42 TC 2 Z9 2 U1 0 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 AUG 3 PY 2015 VL 10 IS 8 AR e0134599 DI 10.1371/journal.pone.0134599 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO1UY UT WOS:000358942400030 PM 26237513 ER PT J AU McElcheran, CE Yang, BS Anderson, KJT Golenstani-Rad, L Graham, SJ AF McElcheran, Clare E. Yang, Benson Anderson, Kevan J. T. Golenstani-Rad, Laleh Graham, Simon J. TI Investigation of Parallel Radiofrequency Transmission for the Reduction of Heating in Long Conductive Leads in 3 Tesla Magnetic Resonance Imaging SO PLOS ONE LA English DT Article ID DEEP BRAIN-STIMULATION; ABSORPTION RATE; RF TRANSMISSION; PULSE DESIGN; MRI SAFETY; 8 CHANNELS; DEVICES; EXCITATION; IMPLANT; WIRES AB Deep Brain Stimulation (DBS) is increasingly used to treat a variety of brain diseases by sending electrical impulses to deep brain nuclei through long, electrically conductive leads. Magnetic resonance imaging (MRI) of patients pre- and post-implantation is desirable to target and position the implant, to evaluate possible side-effects and to examine DBS patients who have other health conditions. Although MRI is the preferred modality for pre-operative planning, MRI post-implantation is limited due to the risk of high local power deposition, and therefore tissue heating, at the tip of the lead. The localized power deposition arises from currents induced in the leads caused by coupling with the radiofrequency (RF) transmission field during imaging. In the present work, parallel RF transmission (pTx) is used to tailor the RF electric field to suppress coupling effects. Electromagnetic simulations were performed for three pTx coil configurations with 2, 4, and 8-elements, respectively. Optimal input voltages to minimize coupling, while maintaining RF magnetic field homogeneity, were determined for all configurations using a Nelder-Mead optimization algorithm. Resulting electric and magnetic fields were compared to that of a 16-rung birdcage coil. Experimental validation was performed with a custom-built 4-element pTx coil. In simulation, 95-99% reduction of the electric field at the tip of the lead was observed between the various pTx coil configurations and the birdcage coil. Maximal reduction in E-field was obtained with the 8-element pTx coil. Magnetic field homogeneity was comparable to the birdcage coil for the 4- and 8-element pTx configurations. In experiment, a temperature increase of 2+/-0.15 degrees C was observed at the tip of the wire using the birdcage coil, whereas negligible increase (0.2+/-0.15 degrees C) was observed with the optimized pTx system. Although further research is required, these initial results suggest that the concept of optimizing pTx to reduce DBS heating effects holds considerable promise. C1 [McElcheran, Clare E.; Yang, Benson; Anderson, Kevan J. T.; Graham, Simon J.] Sunnybrook Hlth Sci Inst, Phys Sci Platform, Toronto, ON, Canada. [McElcheran, Clare E.; Graham, Simon J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Golenstani-Rad, Laleh] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP McElcheran, CE (reprint author), Sunnybrook Hlth Sci Inst, Phys Sci Platform, Toronto, ON, Canada. EM mcelcher@sri.utoronto.ca FU Natural Sciences and Engineering Research Council of Canada (NSERC) [1010219] FX Funding for this research was provided by a Discovery Grant awarded to Dr. Graham from the Natural Sciences and Engineering Research Council of Canada (NSERC: grant number 1010219, http://www.nserc-crsng.gc.ca/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 2 Z9 2 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 3 PY 2015 VL 10 IS 8 AR e0134379 DI 10.1371/journal.pone.0134379 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO1UY UT WOS:000358942400025 PM 26237218 ER PT J AU Reisner, SL Vetters, R White, JM Cohen, EL LeClerc, M Zaslow, S Wolfrum, S Mimiaga, MJ AF Reisner, Sari L. Vetters, Ralph White, Jaclyn M. Cohen, Elijah L. LeClerc, M. Zaslow, Shayne Wolfrum, Sarah Mimiaga, Matthew J. TI Laboratory-confirmed HIV and sexually transmitted infection seropositivity and risk behavior among sexually active transgender patients at an adolescent and young adult urban community health center SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE youth; transgender; HIV; STI ID SURVEILLANCE SYSTEM; NONTRANSGENDER MEN; UNITED-STATES; PARTNER TYPE; SEX WORK; WOMEN; PREVENTION; GENDER; YOUTH; LIFE AB The sexual health of transgender adolescents and young adults who present for health care in urban community health centers is understudied. A retrospective review of electronic health record (EHR) data was conducted from 180 transgender patients aged 12-29 years seen for one or more health-care visits between 2001 and 2010 at an urban community health center serving youth in Boston, MA. Analyses were restricted to 145 sexually active transgender youth (87.3% of the sample). Laboratory-confirmed HIV and sexually transmitted infections (STIs) seroprevalence, demographics, sexual risk behavior, and structural and psychosocial risk indicators were extracted from the EHR. Analyses were descriptively focused for HIV and STIs. Stratified multivariable logistic regression models were fit for male-to-female (MTF) and female-to-male (FTM) patients separately to examine factors associated with any unprotected anal and/or vaginal sex (UAVS). The mean age was 20.0 (SD = 2.9); 21.7% people of color, 46.9% white (non-Hispanic), 21.4% race/ethnicity unknown; 43.4% MTF, and 56.6% FTM; and 68.3% were on cross-sex hormones. Prevalence of STIs: 4.8% HIV, 2.8% herpes simplex virus, 2.8% syphilis, 2.1% chlamydia, 2.1% gonorrhea, 2.8% hepatitis C, 1.4% human papilloma virus. Only gonorrhea prevalence significantly differed by gender identity (MTF 2.1% vs. 0.0% FTM; p = 0.046). Nearly half (47.6%) of the sample engaged in UAVS (52.4% MTF, 43.9% FTM, p = 0.311). FTM more frequently had a primary sex partner compared to MTF (48.8% vs. 25.4%; p = 0.004); MTF more frequently had a casual sex partner than FTM (69.8% vs. 42.7% p = 0.001). In multivariable models, MTF youth who were younger in age, white non-Hispanic, and reported a primary sex partner had increased odds of UAVS; whereas, FTM youth reporting a casual sex partner and current alcohol use had increased odds of UAVS (all p < 0.05). Factors associated with sexual risk differ for MTF and FTM youth. Partner type appears pivotal to understanding sexual risk in transgender adolescents and young adults. HIV and STI prevention efforts, including early intervention efforts, are needed in community-based settings serving transgender youth that attend to sex-specific (biological) and gender-related (social) pathways. C1 [Reisner, Sari L.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Reisner, Sari L.; White, Jaclyn M.; Cohen, Elijah L.; Zaslow, Shayne; Wolfrum, Sarah; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Vetters, Ralph] Fenway Hlth, Sidney Borum Jr Hlth Ctr, Boston, MA USA. [White, Jaclyn M.] Yale Univ, Chron Dis Epidemiol, Sch Publ Hlth, New Haven, CT USA. [LeClerc, M.] Boston Univ, Sch Publ Hlth, Community Hlth Sci, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Reisner, SL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM sreisner@fenwayhealth.org RI Dyson, Alastair/L-8938-2015 OI Dyson, Alastair/0000-0002-1042-3475 FU Fenway Institute at Fenway Health; National Institute of Mental Health (NIMH) [R01MH094323]; NIMH [T32MH020031, P30MH062294] FX This work was supported by The Fenway Institute at Fenway Health. Dr Reisner and Dr Mimiaga's time was partially supported by National Institute of Mental Health (NIMH) [R01MH094323]. Ms White's time was supported by [Award Number T32MH020031], [Award Number P30MH062294] from NIMH. NR 38 TC 5 Z9 5 U1 1 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD AUG 3 PY 2015 VL 27 IS 8 BP 1031 EP 1036 DI 10.1080/09540121.2015.1020750 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA CH4ZB UT WOS:000354042200015 PM 25790139 ER PT J AU Magidson, JF Biello, KB Safren, SA Rosenberger, JG Novak, DS Mayer, KH Mimiaga, MJ AF Magidson, Jessica F. Biello, Katie B. Safren, Steven A. Rosenberger, Joshua G. Novak, David S. Mayer, Kenneth H. Mimiaga, Matthew J. TI Engagement in HIV care and sexual transmission risk behavior among men who have sex with men using online social/sexual networking in Latin America SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE adherence; Latin America; secondary prevention; men who have sex with men; antiretroviral therapy ID MIDDLE-INCOME COUNTRIES; ANTIRETROVIRAL THERAPY; INFECTION; PREVENTION; EPIDEMIC; TRENDS; PERU; MSM AB HIV/AIDS in Latin America is concentrated among men who have sex with men (MSM). However, accurate estimates of engagement in HIV care in this population can be difficult to ascertain because many do not self-identify as MSM. Given evidence of decreased HIV transmissibility in the context of antiretroviral therapy (ART) adherence, identifying individuals not in care who are engaging in HIV transmission risk behavior is crucial for secondary prevention. Primary aims of this study were to examine engagement in care from testing to ART adherence among MSM using online social/sexual networking across Latin America, and whether individuals not in care at each step reported greater sexual transmission risk behavior than those in care. In the overall sample (n = 28,779), approximately 75% reported ever being tested for HIV, and 9% reported having received an HIV diagnosis. Among known HIV-infected individuals, 20% reported not being in care, 30% reported not taking ART, and 55% reported less than 100% ART adherence. Over one-third of HIV-infected individuals reported sexual HIV transmission risk behavior, defined as unprotected anal intercourse (UAI) with a male partner of different/unknown HIV serostatus in the past three months. HIV-infected individuals not engaged in care more often reported UAI compared to those in care (OR = 1.29; 95% CI = 1.01-1.66). Although not statistically significant, HIV-infected individuals not on ART more often reported UAI compared to those on ART (OR = 1.18; 95% CI = 0.94-1.47). Individuals who reported less than 100% ART adherence more often reported UAI compared to individuals with 100% adherence (OR = 1.55; 95% CI = 1.26-1.90). Findings demonstrate that a substantial portion of HIV-infected MSM in Latin America who are likely not virologically suppressed from lack of ART use or adherence report sexual HIV transmission risk. Tailoring secondary HIV prevention for MSM in Latin America who are not in HIV care or adherent to ART may be warranted. C1 [Magidson, Jessica F.; Safren, Steven A.; Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Biello, Katie B.; Safren, Steven A.; Mayer, Kenneth H.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Biello, Katie B.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rosenberger, Joshua G.] George Mason Univ, Dept Global & Community Hlth, Fairfax, VA 22030 USA. [Novak, David S.] Online Buddies Inc, OLB Res Inst, Cambridge, MA USA. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Magidson, JF (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM jmagidson@partners.org FU NIH [T32MH093310, K24MH094214]; Harvard University Center for AIDS Research (CFAR) NIH [P30AI060354] FX Dr Magidson's work on this study was supported by NIH [grant number T32MH093310]. Dr Safren was supported by NIH [grant number K24MH094214]. Dr Mayer and Dr Safren were also supported by the Harvard University Center for AIDS Research (CFAR) NIH [grant number P30AI060354]. This study was supported by consultation from other members of the HU CFAR Social and Behavioral Sciences Core. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 26 TC 2 Z9 2 U1 2 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD AUG 3 PY 2015 VL 27 IS 8 BP 1055 EP 1062 DI 10.1080/09540121.2015.1017796 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA CH4ZB UT WOS:000354042200019 PM 25738655 ER PT J AU Wilczynski, C Shah, L Emanuele, MA Emanuele, N Mazhari, A AF Wilczynski, Cory Shah, Lisa Emanuele, Mary Ann Emanuele, Nicholas Mazhari, Alaleh TI SELECTIVE HYPOALDOSTERONISM: A REVIEW SO ENDOCRINE PRACTICE LA English DT Review ID RENAL TUBULAR-ACIDOSIS; CRITICALLY-ILL PATIENT; HYPERRENINEMIC HYPOALDOSTERONISM; HYPORENINEMIC HYPOALDOSTERONISM; ALDOSTERONE DEFICIENCY; ANGIOTENSIN-II; UNILATERAL ADRENALECTOMY; PROLONGED HYPERKALEMIA; POTASSIUM HOMEOSTASIS; METABOLIC-ACIDOSIS AB Objective: Selective hypoaldosteronism (SH) is a condition manifested by hyperkalemia due to low aldosterone secretion with normal cortisol. One of the obstacles in diagnosis is the awareness of the condition itself. The objective of this review is to highlight what is known about the epidemiology, pathophysiology, etiology, presentation, diagnosis, and treatment of SH. Methods: Literature search was performed on PubMed and Ovid Medline for articles which contained hypoaldosteronism as a major topic. Results: The recent literature on this topic is surprisingly limited. Few recent review articles were found, none of which were in English and less than 5 years old. Case reports and genetic literature were also included in this review, as they contain the most recent reports of SH in the literature. Conclusion: Awareness about SH will hopefully help physicians to identify patients at risk as well as decide on treatment if any therapy is required. C1 [Wilczynski, Cory; Shah, Lisa; Emanuele, Mary Ann; Emanuele, Nicholas; Mazhari, Alaleh] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Wilczynski, Cory; Shah, Lisa; Emanuele, Mary Ann; Emanuele, Nicholas] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Wilczynski, C (reprint author), 2160 South First Ave, Maywood, IL 60153 USA. EM cwilczynski@gmail.com NR 77 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD AUG PY 2015 VL 21 IS 8 BP 957 EP 965 DI 10.4158/EP14551.RA PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO7LT UT WOS:000377964800012 PM 26121445 ER PT J AU Luciano, JA Kautza, B Darwiche, S Martinez, S Stratimirovic, S Waltz, P Sperry, J Rosengart, M Shiva, S Zuckerbraun, BS AF Luciano, Jason A. Kautza, Benjamin Darwiche, Sophie Martinez, Silvia Stratimirovic, Sladjana Waltz, Paul Sperry, Jason Rosengart, Matthew Shiva, Sruti Zuckerbraun, Brian S. TI SIRTUIN 1 AGONIST MINIMIZES INJURY AND IMPROVES THE IMMUNE RESPONSE FOLLOWING TRAUMATIC SHOCK SO SHOCK LA English DT Article DE Innate immune response; mitochondrial biogenesis; PGC1 alpha; trauma-hemorrhage ID NF-KAPPA-B; MITOCHONDRIAL BIOGENESIS; HEMORRHAGIC-SHOCK; ISCHEMIA-REPERFUSION; NITRIC-OXIDE; CELL-DEATH; ACTIVATION; DYSFUNCTION; RESUSCITATION; EXPRESSION AB Survival from traumatic injury requires a coordinated and controlled inflammatory and immune response. Mitochondrial and metabolic responses to stress have been shown to play a role in these inflammatory and immune responses. We hypothesized that increases in mitochondrial biogenesis via a sirtuin 1 agonist would decrease tissue injury and partially ameliorate the immunosuppression seen following trauma. C57Bl/6 mice were subjected to a multiple trauma model. Mice were pretreated with either 100 mg/kg per day of the sirtuin 1 agonist, Srt1720, via oral gavage for 2 days prior to trauma and extended until the day the animals were killed, or they were pretreated with peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1 alpha) siRNA via hydrodynamic tail vein injection 48 h prior to trauma. Markers for mitochondrial function and biogenesis were measured in addition to splenocyte proliferative capacity and bacterial clearance. Srt1720 was noted to improve mitochondrial biogenesis, mitochondrial function, and complex IV activity following traumatic injury (P < 0.05), whereas knockdown of PGC1 alpha resulted in exacerbation of mitochondrial dysfunction (P < 0.05). These changes in mitochondrial function were associated with altered severity of hepatic injury with significant reductions in serum alanine aminotransferase levels seen in mice treated with srt1720. Splenocyte proliferative capacity and intraperitoneal bacterial clearance were evaluated as markers for overall immune function following trauma-hemorrhage. Treatment with Srt1720 minimized the trauma-induced decreases in splenocyte proliferation (P < 0.05), whereas treatment with PGC1 alpha siRNA led to diminished bacterial clearance. The PGC1 alpha signaling pathway is an important regulator of mitochondrial function and biogenesis, which can potentially be harnessed to protect against hepatic injury and minimize the immunosuppression that is seen following trauma-hemorrhage. C1 [Luciano, Jason A.; Kautza, Benjamin; Darwiche, Sophie; Martinez, Silvia; Stratimirovic, Sladjana; Waltz, Paul; Sperry, Jason; Rosengart, Matthew; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Stratimirovic, Sladjana; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sperry, Jason; Rosengart, Matthew] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. [Shiva, Sruti] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Shiva, Sruti; Zuckerbraun, Brian S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA. [Zuckerbraun, Brian S.] Univ Pittsburgh, Ctr Crit Care Nephrol, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), F1267 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu FU National Institutes of Health [R01GM082830]; Veterans Affairs Merit Award [1I01BX000566]; Department of Defense [DM102439] FX This work is supported by National Institutes of Health (grant R01GM082830 to B.S.Z.), Veterans Affairs Merit Award (grant 1I01BX000566 to B.S.Z.), and the Department of Defense (grant DM102439 to B.S.Z.) NR 34 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD AUG PY 2015 VL 44 SU 1 BP 149 EP 155 DI 10.1097/SHK.0000000000000412 PG 7 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA DO3NA UT WOS:000377687100021 PM 26009827 ER PT J AU Malley, A Kenner, C Kim, T Blakeney, B AF Malley, Ann Kenner, Carole Kim, Tiffany Blakeney, Barbara TI The Role of the Nurse and the Preoperative Assessment in Patient Transitions SO AORN JOURNAL LA English DT Article DE transitions; multidimensional communication; transfer of care; preoperative assessment ID INFORMATION-TRANSFER; CARE TRANSITIONS; SURGICAL CARE; SAFETY; COMMUNICATION; DISCHARGE; SURGERY; MODEL; ROOM AB Transitions in care in the perioperative environment are numerous and should be considered high-risk endeavors. The preoperative area is the first transition in care for a surgical patient and should be considered a critical dimension of care transition. The purposes of this study were to identify nursing's contributions to transitions in care in the perioperative environment and to identify the role of the preoperative assessment in this transition. Qualitative descriptive design was used. Focus groups were conducted with 24 nurses in a 975-bed medical center. The themes that arose in the focus groups were: (1) understanding patient vulnerabilities, (2) multidimensional communication, (3) managing patients' expectations, and (4) nursing's role in compensating for gaps. We conclude that the nurse's role in the preoperative assessment during the transition of preoperative care is that of advocate who identifies the patient's needs and risk factors that may be affected by the surgical experience. This study suggests that the nursing preoperative assessment can be useful in identifying and defining patients' risk factors not just for surgery, but for the entire perioperative care trajectory. (C) AORN, Inc, 2015. C1 [Malley, Ann] Univ Penn, NewCourtland Ctr Transit & Hlth, Philadelphia, PA 19104 USA. [Kenner, Carole] Coll New Jersey, Sch Nursing Hlth & Exercise Sci, Ewing, NJ USA. [Kim, Tiffany] Northeastern Univ, Bouve Coll Hlth Sci, Sch Nursing, Boston, MA 02115 USA. [Blakeney, Barbara] Massachusetts Gen Hosp, Ctr Innovat, Boston, MA 02114 USA. RP Malley, A (reprint author), Univ Penn, NewCourtland Ctr Transit & Hlth, Philadelphia, PA 19104 USA. FU NINR NIH HHS [T32 NR009356] NR 30 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0001-2092 J9 ASSOC OPER ROOM NURS JI AORN J. PD AUG PY 2015 VL 102 IS 2 AR 181.e1 DI 10.1016/j.aorn.2015.06.004 PG 9 WC Nursing SC Nursing GA DI4CP UT WOS:000373448200012 PM 26227526 ER PT J AU Abazeed, M Yard, B Adams, D Tamayo, P Hearn, J Chie, EK Schreiber, S Meyerson, M Peacock, C Hammerman, P AF Abazeed, Mohamed Yard, Brian Adams, Drew Tamayo, Pablo Hearn, Jason Chie, Eui Kyu Schreiber, Stuart Meyerson, Matthew Peacock, Craig Hammerman, Peter TI Functional genomic profiling of lung adenocarcinoma identifies BRAF mutations as novel therapeutic targets SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Abazeed, Mohamed; Yard, Brian; Hearn, Jason; Chie, Eui Kyu; Peacock, Craig] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Adams, Drew; Tamayo, Pablo; Schreiber, Stuart] Broad Inst, Cambridge, MA USA. [Meyerson, Matthew] Dana Farber Canc Inst, Cambridge, MA USA. [Hammerman, Peter] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3315 DI 10.1158/1538-7445.AM2015-3315 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597101344 ER PT J AU Abo, RP Lin, L Hunter, SS Dolcen, DN Paquette, RR Laing, A de Waal, L Thorner, AR Ducar, MD Ziaugra, L Hahn, WC Meyerson, ML MacConaill, LE Van Hummelen, P AF Abo, Ryan P. Lin, Ling Hunter, Samuel S. Dolcen, Deniz N. Paquette, Rachel R. Laing, Angelica de Waal, Luc Thorner, Aaron R. Ducar, Matthew D. Ziaugra, Liuda Hahn, William C. Meyerson, Matthew L. MacConaill, Laura E. Van Hummelen, Paul TI Comparative analysis of RNA sequencing methods for characterization of cancer transcriptomics SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Abo, Ryan P.; Lin, Ling; Hunter, Samuel S.; Dolcen, Deniz N.; Paquette, Rachel R.; Laing, Angelica; de Waal, Luc; Thorner, Aaron R.; Ducar, Matthew D.; Ziaugra, Liuda; Hahn, William C.; Meyerson, Matthew L.; MacConaill, Laura E.; Van Hummelen, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4867 DI 10.1158/1538-7445.AM2015-4867 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105052 ER PT J AU Ahronian, LG Sennott, EM Van Allen, EM Wagle, N Kwak, EL Faris, JE Godfrey, JT Nishimura, K Lynch, KD Mermel, CH Lockerman, EL Kalsy, A Gurski, JM Bahl, S Anderka, K Green, LM Lennon, NJ Huynh, TG Mino-Kenudson, M Getz, G Dias-Santagata, D Iafrate, AJ Engelman, JA Garraway, LA Corcoran, RB AF Ahronian, Leanne G. Sennott, Erin M. Van Allen, Eliezer M. Wagle, Nikhil Kwak, Eunice L. Faris, Jason E. Godfrey, Jason T. Nishimura, Koki Lynch, Kerry D. Mermel, Craig H. Lockerman, Elizabeth L. Kalsy, Anuj Gurski, Joseph M. Bahl, Samira Anderka, Kristin Green, Lisa M. Lennon, Niall J. Huynh, Tiffany G. Mino-Kenudson, Mari Getz, Gad Dias-Santagata, Dora Iafrate, A. John Engelman, Jeffrey A. Garraway, Levi A. Corcoran, Ryan B. TI Clinical acquired resistance to RAF inhibitor combinations in BRAF-mutant colorectal cancer through MAPK pathway alterations SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Ahronian, Leanne G.; Sennott, Erin M.; Kwak, Eunice L.; Faris, Jason E.; Godfrey, Jason T.; Nishimura, Koki; Mermel, Craig H.; Lockerman, Elizabeth L.; Kalsy, Anuj; Gurski, Joseph M.; Getz, Gad; Engelman, Jeffrey A.; Corcoran, Ryan B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Van Allen, Eliezer M.; Wagle, Nikhil; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lynch, Kerry D.; Huynh, Tiffany G.; Mino-Kenudson, Mari; Dias-Santagata, Dora; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bahl, Samira; Anderka, Kristin; Green, Lisa M.; Lennon, Niall J.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA LB-055 DI 10.1158/1538-7445.AM2015-LB-055 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100160 ER PT J AU Allen, JE Ishizawa, J El-Deiry, WS Andreeff, M Garnett, M Benes, C AF Allen, Joshua E. Ishizawa, Jo El-Deiry, Wafik S. Andreeff, Michael Garnett, Mathew Benes, Cyril TI In vitro efficacy profiling of ONC201 in cancer cells reveals sensitivity pattern that is consistent with ER stress response SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Allen, Joshua E.] Oncoceutics, Philadelphia, PA USA. [Ishizawa, Jo; Andreeff, Michael] MD Anderson, Houston, TX USA. [El-Deiry, Wafik S.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Garnett, Mathew] Wellcome Trust Sanger Inst, Cambridge, England. [Benes, Cyril] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4475 DI 10.1158/1538-7445.AM2015-4475 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104103 ER PT J AU Amin-Mansour, A Sioletic, S Carter, SL Garraway, LA Demetri, GD George, S Van Allen, EM Wagner, AJ AF Amin-Mansour, Ali Sioletic, Stefano Carter, Scott L. Garraway, Levi A. Demetri, George D. George, Suzanne Van Allen, Eliezer M. Wagner, Andrew J. TI Differential evolution of tumor heterogeneity in leiomyosarcomas and liposarcomas suggested by genomic profiling SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Amin-Mansour, Ali; Carter, Scott L.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Sioletic, Stefano; Garraway, Levi A.; Demetri, George D.; George, Suzanne; Van Allen, Eliezer M.; Wagner, Andrew J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sioletic, Stefano; Garraway, Levi A.; Demetri, George D.; George, Suzanne; Van Allen, Eliezer M.; Wagner, Andrew J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4819 DI 10.1158/1538-7445.AM2015-4819 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105006 ER PT J AU Amzallag, A Yuan, TL Bagni, R Yi, M Stephens, R Ramawamy, S McCormick, F Benes, CH AF Amzallag, Arnaud Yuan, Tina L. Bagni, Rachel Yi, Ming Stephens, Robert Ramawamy, Sridhar McCormick, Frank Benes, Cyril H. TI Querying the RAS genomic network with siRNAs and and flow cytometry: Automatic, multidimensional phenotyping of 135 cancer cell lines by Gaussian mixture fitting and expectation maximization SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Amzallag, Arnaud; Ramawamy, Sridhar; Benes, Cyril H.] Massachusetts Gen Hosp, Charlestown, MA USA. [Yuan, Tina L.; McCormick, Frank] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bagni, Rachel; Yi, Ming; Stephens, Robert] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA LB-247 DI 10.1158/1538-7445.AM2015-LB-247 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100341 ER PT J AU Bailey, ST Westerling, T Brown, M AF Bailey, Shannon T. Westerling, Thomas Brown, Myles TI Estrogen receptor stability is modulated by calpain activity in breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Bailey, Shannon T.; Westerling, Thomas; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA LB-016 DI 10.1158/1538-7445.AM2015-LB-016 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100124 ER PT J AU Best, M Sol, N Kooi, I Nilsson, J Westerman, B Yistra, B Dorsman, J Smit, E Verheui, H Reijneveld, J Tannous, B Wesseling, P Wurdinger, T AF Best, Myron Sol, Nik Kooi, Irsan Nilsson, Jonas Westerman, Bart Yistra, Bauke Dorsman, Josephine Smit, Egbert Verheui, Henk Reijneveld, Jaap Tannous, Bakhos Wesseling, Pieter Wurdinger, Thomas TI Tumor-educated platelets allow for multiclass liquid biopsy-based diagnosis of cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Best, Myron; Sol, Nik; Kooi, Irsan; Westerman, Bart; Yistra, Bauke; Dorsman, Josephine; Smit, Egbert; Verheui, Henk; Reijneveld, Jaap; Wesseling, Pieter; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Nilsson, Jonas] Umea Univ, Umea, Sweden. [Tannous, Bakhos] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA LB-124 DI 10.1158/1538-7445.AM2015-LB-124 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100226 ER PT J AU Brastianos, PK Carter, SL Santagata, S Taylor-Weiner, A Jones, RT Van Allen, E Ligon, KL Tabernero, J Seoane, J Martinez-Saez, E Cahill, D Curry, WT Dunn, IF Paek, SH Van Hummelen, P Thorner, AR Johnson, BE Lin, NU Choueiri, TK Rabin, MS Beroukhim, R Stemmer-Rachamimov, A Meyerson, M Garraway, L Batchelor, T Baselga, J Louis, DN Hahn, WC Getz, G AF Brastianos, Priscilla K. Carter, Scott L. Santagata, Sandro Taylor-Weiner, Amaro Jones, Robert T. Van Allen, Eli Ligon, Keith L. Tabernero, Josep Seoane, Joan Martinez-Saez, Elena Cahill, Daniel Curry, William T. Dunn, Ian F. Paek, Sun Ha Van Hummelen, Paul Thorner, Aaron R. Johnson, Bruce E. Lin, Nancy U. Choueiri, Toni K. Rabin, Michael S. Beroukhim, Rameen Stemmer-Rachamimov, Anat Meyerson, Matthew Garraway, Levi Batchelor, Tracy Baselga, Jose Louis, David N. Hahn, William C. Getz, Gad TI Genomic characterization of brain metastases reveals divergent evolution and metastasis specific mutations SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Brastianos, Priscilla K.; Cahill, Daniel; Curry, William T.; Stemmer-Rachamimov, Anat; Batchelor, Tracy; Louis, David N.; Getz, Gad] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carter, Scott L.; Taylor-Weiner, Amaro] Broad Inst Harvard & MIT, Cambridge, MA USA. [Santagata, Sandro; Dunn, Ian F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jones, Robert T.; Van Allen, Eli; Ligon, Keith L.; Van Hummelen, Paul; Thorner, Aaron R.; Johnson, Bruce E.; Lin, Nancy U.; Choueiri, Toni K.; Rabin, Michael S.; Beroukhim, Rameen; Meyerson, Matthew; Garraway, Levi; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tabernero, Josep; Seoane, Joan; Martinez-Saez, Elena] Vall DHebron Univ Hosp, Barcelona, Spain. [Paek, Sun Ha] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4727 DI 10.1158/1538-7445.AM2015-4727 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104355 ER PT J AU Braunstein, LZ Chen, MH Dosoretz, DE Salenius, S Katin, M Nanda, A D'Amico, AV AF Braunstein, Lior Z. Chen, Ming-Hui Dosoretz, Daniel E. Salenius, Sharon Katin, Michael Nanda, Akash D'Amico, Anthony V. TI Whole pelvis versus prostate-only radiotherapy with or without short course androgen deprivation therapy and mortality risk SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Braunstein, Lior Z.] Harvard Radiat Oncol Program, Boston, MA USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Dosoretz, Daniel E.; Salenius, Sharon; Katin, Michael] 21st Century Oncol, Ft Myers, FL USA. [Nanda, Akash] MD Anderson Canc Ctr Orlando, Orlando, FL USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3438 DI 10.1158/1538-7445.AM2015-3438 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597101464 ER PT J AU Bucur, O Irshad, H Montaser-Kouhsari, L Knoblauch, NW Oh, EY Nowak, J Beck, AH AF Bucur, Octavian Irshad, Humayun Montaser-Kouhsari, Laleh Knoblauch, Nicholas W. Oh, Eun-Yeong Nowak, Jonathan Beck, Andrew H. TI 3D morphological hallmarks of breast carcinogenesis: Diagnosis of non-invasive and invasive breast cancer with Lightsheet microscopy SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Bucur, Octavian; Irshad, Humayun; Montaser-Kouhsari, Laleh; Knoblauch, Nicholas W.; Oh, Eun-Yeong; Nowak, Jonathan; Beck, Andrew H.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3477 DI 10.1158/1538-7445.AM2015-3477 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597102018 ER PT J AU Burris, HA Shaw, AT Bauer, TM Farago, AF Doebele, RC Smith, S Nanda, N Cruickshank, S Low, JA Brose, MS AF Burris, Howard A. Shaw, Alice T. Bauer, Todd M. Farago, Anna F. Doebele, Robert C. Smith, Steven Nanda, Nisha Cruickshank, Scott Low, Jennifer A. Brose, Marcia S. TI Pharmacokinetics (PK) of LOXO-101 during the first-in-human Phase I study in patients with advanced solid tumors: Interim update SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Burris, Howard A.; Bauer, Todd M.] Sarah Cannon Res Inst, Nashville, TN USA. [Shaw, Alice T.; Farago, Anna F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Doebele, Robert C.] Univ Colorado, Aurora, CO USA. [Smith, Steven; Nanda, Nisha; Cruickshank, Scott; Low, Jennifer A.] Loxo Oncol, San Francisco, CA USA. [Brose, Marcia S.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4529 DI 10.1158/1538-7445.AM2015-4529 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104156 ER PT J AU Camargo, MC Bowlby, R Chu, A Pedamallu, CS Thorsson, V Elmore, S Mungall, A Bass, A Gulley, ML Rabkin, CS AF Camargo, M. Constanza Bowlby, Reanne Chu, Andy Pedamallu, Chandra S. Thorsson, Vesteinn Elmore, Sandra Mungall, Andrew Bass, Adam Gulley, Margaret L. Rabkin, Charles S. TI Validation and calibration of next-generation sequencing to identify Epstein-Barr Virus-positive gastric cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Camargo, M. Constanza; Rabkin, Charles S.] NCI, Bethesda, MD 20892 USA. [Bowlby, Reanne; Chu, Andy; Mungall, Andrew] BC Canc Agcy, Vancouver, BC, Canada. [Pedamallu, Chandra S.] Broad Inst, Cambridge, MA USA. [Thorsson, Vesteinn] Inst Syst Biol, Seattle, WA USA. [Elmore, Sandra; Gulley, Margaret L.] Univ N Carolina, Chapel Hill, NC USA. [Bass, Adam] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Camargo, M. Constanza/R-9891-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4621 DI 10.1158/1538-7445.AM2015-4621 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104249 ER PT J AU Campbell, J Lathan, C Sholl, L Ducar, M Vega, M Lin, L Thorner, A Faris, N Van Hummelen, P Osarogiagbon, R Meyerson, M MacConaill, L AF Campbell, Joshua Lathan, Christopher Sholl, Lynette Ducar, Matthew Vega, Mikenah Lin, Ling Thorner, Aaron Faris, Nick Van Hummelen, Paul Osarogiagbon, Raymond Meyerson, Matthew MacConaill, Laura TI Comparing the mutational landscape of African American and Caucasian lung cancers SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Campbell, Joshua] Broad Inst, Boston, MA USA. [Lathan, Christopher; Ducar, Matthew; Vega, Mikenah; Lin, Ling; Thorner, Aaron; Van Hummelen, Paul; Meyerson, Matthew; MacConaill, Laura] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sholl, Lynette] Brigham & Womens Hosp, Boston, MA 02115 USA. [Faris, Nick; Osarogiagbon, Raymond] Baptist Mem Hlth Care, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3886 DI 10.1158/1538-7445.AM2015-3886 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597102410 ER PT J AU Cato, L Neeb, A Adelmant, G Ficarro, S Westerling, T Marto, JA Cato, AC Brown, M AF Cato, Laura Neeb, Antje Adelmant, Guillaume Ficarro, Scott Westerling, Thomas Marto, Jarrod A. Cato, Andrew C. Brown, Myles TI Control of androgen receptor function by the genomic action of the cochaperone Bag-1L SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Cato, Laura; Adelmant, Guillaume; Ficarro, Scott; Westerling, Thomas; Marto, Jarrod A.; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neeb, Antje; Cato, Andrew C.] Karlsruhe Inst Technol, D-76021 Karlsruhe, Germany. RI Cato, Andrew/H-2071-2013 OI Cato, Andrew/0000-0001-8508-3834 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4677 DI 10.1158/1538-7445.AM2015-4677 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104305 ER PT J AU Chong, C Ercan, D Bahcall, M Capelletti, M Gray, N Janne, P AF Chong, Curtis Ercan, Dalia Bahcall, Magda Capelletti, Marzia Gray, Nathanael Janne, Pasi TI Identification of existing targeted agents that inhibit NTRK and ROS1 in lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Chong, Curtis; Ercan, Dalia; Bahcall, Magda; Capelletti, Marzia; Gray, Nathanael; Janne, Pasi] Dana Farber Canc Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3644 DI 10.1158/1538-7445.AM2015-3644 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597102183 ER PT J AU Corcoran, RB Ahronian, LG Van Allen, E Coffee, EM Wagle, N Kwak, EL Faris, JE Iafrate, AJ Garraway, LA Engelman, JA AF Corcoran, Ryan B. Ahronian, Leanne G. Van Allen, Eliezer Coffee, Erin M. Wagle, Nikhil Kwak, Eunice L. Faris, Jason E. Iafrate, A. John Garraway, Levi A. Engelman, Jeffrey A. TI Clinical acquired resistance to RAF inhibitor combinations in BRAF mutant colorectal cancer through MAPK pathway alterations SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Corcoran, Ryan B.; Ahronian, Leanne G.; Coffee, Erin M.; Kwak, Eunice L.; Faris, Jason E.; Iafrate, A. John; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Van Allen, Eliezer; Wagle, Nikhil; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA NG04 DI 10.1158/1538-7445.AM2015-NG04 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100403 ER PT J AU Dickler, M Bardia, A Mayer, I Winer, E Rix, P Hager, J Chen, M Chan, I Chow-Maneval, E Arteaga, C Baselga, J AF Dickler, Maura Bardia, Aditya Mayer, Ingrid Winer, Eric Rix, Peter Hager, Jeff Chen, Meng Chan, Iris Chow-Maneval, Edna Arteaga, Carlos Baselga, Jose TI A first-in-human phase I study to evaluate the oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with estrogen receptor+HER2-, advanced/metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Dickler, Maura; Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bardia, Aditya] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Mayer, Ingrid; Arteaga, Carlos] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Winer, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rix, Peter; Hager, Jeff; Chow-Maneval, Edna] Seragon Pharmaceut, San Diego, CA USA. [Chen, Meng; Chan, Iris] Genentech Inc, San Francisco, CA 94080 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT231 DI 10.1158/1538-7445.AM2015-CT231 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100065 ER PT J AU Duarte, LF Young, ARJ Wang, ZC Wu, HA Panda, T Kou, Y Kapoor, A Hasson, D Mills, NR Ma'ayan, A Narita, M Bernstein, E AF Duarte, Luis F. Young, Andrew R. J. Wang, Zichen Wu, Hsan-Au Panda, Taniya Kou, Yan Kapoor, Avnish Hasson, Dan Mills, Nicholas R. Ma'ayan, Avi Narita, Masashi Bernstein, Emily TI Histone tail alterations in cellular senescence SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Duarte, Luis F.; Ma'ayan, Avi] Mt Sinai, New York, NY USA. [Young, Andrew R. J.] Texas Tech Univ, Lubbock, TX 79409 USA. [Wang, Zichen; Panda, Taniya; Kou, Yan; Kapoor, Avnish; Bernstein, Emily] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Wu, Hsan-Au] Columbia Univ, New York, NY USA. [Hasson, Dan] Karolinska Inst, Stockholm, Sweden. [Mills, Nicholas R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Narita, Masashi] Canc Res UK Cambridge Res Inst, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA SY10-04 DI 10.1158/1538-7445.AM2015-SY10-04 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100426 ER PT J AU Ebot, EM Gerke, T Tyekucheva, S Labbe, DP Zadra, G Kelly, RS Bowden, M Rider, JR Wilson, KM Martin, NE Brown, M Vander Heiden, MG Giovannucci, EL Loda, M Mucci, LA AF Ebot, Ericka M. Gerke, Travis Tyekucheva, Svitlana Labbe, David P. Zadra, Giorgia Kelly, Rachel S. Bowden, Michaela Rider, Jennifer R. Wilson, Kathryn M. Martin, Neil E. Brown, Myles Vander Heiden, Matthew G. Giovannucci, Edward L. Loda, Massimo Mucci, Lorelei A. TI Identifying obesity-linked gene expression changes in prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Ebot, Ericka M.; Gerke, Travis; Kelly, Rachel S.; Rider, Jennifer R.; Wilson, Kathryn M.; Giovannucci, Edward L.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Tyekucheva, Svitlana; Labbe, David P.; Zadra, Giorgia; Bowden, Michaela; Martin, Neil E.; Brown, Myles; Loda, Massimo] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vander Heiden, Matthew G.] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4686 DI 10.1158/1538-7445.AM2015-4686 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104314 ER PT J AU Etchin, J Le, BT Berezovskaya, A Conway, AS Chen, WC Kentsis, A Mansour, MR Stone, RM Galinsky, IA DeAngelo, DJ McCauley, D Kauffman, M Shacham, S Wang, JCY Kung, AL Look, T AF Etchin, Julia Le, Bonnie Thi Berezovskaya, Alla Conway, Amy S. Chen, Weihsu C. Kentsis, Alex Mansour, Marc R. Stone, Richard M. Galinsky, Ilene A. DeAngelo, Daniel J. McCauley, Dilara Kauffman, Michael Shacham, Sharon Wang, Jean C. Y. Kung, Andrew L. Look, Thomas TI Selective inhibitor of nuclear exporter CRM1/XPO1, Selinexor (KPT-330), exhibits remarkable activity against AML leukemia-initiating cells while sparing normal hematopoietic cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Etchin, Julia; Le, Bonnie Thi; Berezovskaya, Alla; Conway, Amy S.; Mansour, Marc R.; Stone, Richard M.; Galinsky, Ilene A.; DeAngelo, Daniel J.; Look, Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Weihsu C.; Wang, Jean C. Y.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Kentsis, Alex] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [McCauley, Dilara; Kauffman, Michael; Shacham, Sharon] Karyopharm Therapeut, Newton, MA USA. [Kung, Andrew L.] Columbia Univ, Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4445 DI 10.1158/1538-7445.AM2015-4445 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104073 ER PT J AU Fendler, B Abo, R Hunter, S Ducar, M Garcia, E Van Hummelen, P Lindeman, N MacConaill, L AF Fendler, Bernard Abo, Ryan Hunter, Samuel Ducar, Matthew Garcia, Elizabeth Van Hummelen, Paul Lindeman, Neal MacConaill, Laura TI Identifying copy number alterations from targeted sequencing data SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Fendler, Bernard; Garcia, Elizabeth; Lindeman, Neal] Brigham & Womens Hosp, Boston, MA 02115 USA. [Abo, Ryan; Hunter, Samuel; Ducar, Matthew; Van Hummelen, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. [MacConaill, Laura] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4850 DI 10.1158/1538-7445.AM2015-4850 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105035 ER PT J AU Gao, X Sholl, LM Nishino, M Heng, J Janne, PA Oxnard, GR AF Gao, Xin Sholl, Lynette M. Nishino, Mizuki Heng, Jennifer Janne, Pasi A. Oxnard, Geoffrey R. TI 5 ' deletion on ALK break-apart FISH and risk of false positive results SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Gao, Xin] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sholl, Lynette M.; Nishino, Mizuki; Heng, Jennifer; Janne, Pasi A.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4250 DI 10.1158/1538-7445.AM2015-4250 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597103334 ER PT J AU Garcia, EP Ligon, AH Abo, RP Dal Cin, PS Weremowicz, S Shivdasani, P Davineni, PK Zepfl, DL Ducar, MD Van Hummelen, P Jia, YH Kuo, FC Sholll, LM MacConaill, LE Lindeman, NI AF Garcia, Elizabeth P. Ligon, Azra H. Abo, Ryan P. Dal Cin, Paola S. Weremowicz, Stanislawa Shivdasani, Priyanka Davineni, Phani K. Zepfl, Dimity L. Ducar, Matthew D. Van Hummelen, Paul Jia, Yonghui Kuo, Frank C. Sholll, Lynette M. MacConaill, Laura E. Lindeman, Neal I. TI Detection of gene rearrangements using OncoPanel: a targeted next-generation sequencing assay SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Garcia, Elizabeth P.; Ligon, Azra H.; Dal Cin, Paola S.; Weremowicz, Stanislawa; Shivdasani, Priyanka; Davineni, Phani K.; Zepfl, Dimity L.; Jia, Yonghui; Kuo, Frank C.; Sholll, Lynette M.; MacConaill, Laura E.; Lindeman, Neal I.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Abo, Ryan P.; Ducar, Matthew D.; Van Hummelen, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2991 DI 10.1158/1538-7445.AM2015-2991 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597101043 ER PT J AU Garman, B Krepler, C Sproesser, K Brafford, P Wilson, M Wubbenhorst, B Amaravadi, R Bennett, J Beqiri, M Davies, M Elder, D Flaherty, K Frederick, D Gangadhar, TC Guarino, M Hoon, D Karakousis, G Mitra, N Petrelli, NJ Schuchter, L Shannan, B Wargo, J Xiao, M Xu, W Xu, XW Herlyn, M Nathanson, K AF Garman, Bradley Krepler, Clemens Sproesser, Katrin Brafford, Patrica Wilson, Melissa Wubbenhorst, Bradley Amaravadi, Ravi Bennett, Joseph Beqiri, Marilda Davies, Michael Elder, David Flaherty, Keith Frederick, Dennie Gangadhar, Tara C. Guarino, Michael Hoon, David Karakousis, Giorgos Mitra, Nandita Petrelli, Nicholas J. Schuchter, Lynn Shannan, Batool Wargo, Jennifer Xiao, Min Xu, Wei Xu, Xaiowei Herlyn, Meenhard Nathanson, Katherine TI Targeted, massively parallel sequencing identifies novel genetic subsets of cutaneous melanoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Garman, Bradley; Wubbenhorst, Bradley; Mitra, Nandita; Nathanson, Katherine] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Krepler, Clemens; Sproesser, Katrin; Brafford, Patrica; Beqiri, Marilda; Shannan, Batool; Xiao, Min; Herlyn, Meenhard] Melanoma Res Ctr, Wistar Inst, Philadelphia, PA USA. [Wilson, Melissa] NYU Langone Med Ctr, NYU Sch Med, Perlmutter Canc Ctr, New York, NY USA. [Amaravadi, Ravi; Elder, David; Gangadhar, Tara C.; Karakousis, Giorgos; Schuchter, Lynn; Xu, Wei; Xu, Xaiowei] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Bennett, Joseph; Guarino, Michael; Petrelli, Nicholas J.] Helen F Graham Canc Ctr, Newark, DE USA. [Davies, Michael; Wargo, Jennifer] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Flaherty, Keith; Frederick, Dennie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoon, David] John Wayne Canc Inst, Santa Monica, CA USA. OI Wilson, Melissa/0000-0002-5391-7838 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4668 DI 10.1158/1538-7445.AM2015-4668 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104296 ER PT J AU Garon, EB Rizvi, N Hui, RN Leighl, NB Balmanoukian, AS Eder, JP Patnaik, A Aggarwal, C Gubens, MA Horn, L Carcereny, E Ahn, MJ Felip, E Lee, JS Zhang, J Rangwala, RA Lubiniecki, GM Roach, CM Emancipator, K Gandhi, L AF Garon, Edward B. Rizvi, Naiyer Hui, Rina Leighl, Natasha B. Balmanoukian, Ani S. Eder, Joseph P. Patnaik, Amita Aggarwal, Charu Gubens, Matthew A. Horn, Leora Carcereny, Enric Ahn, Myung-Ju Felip, Enriqueta Lee, Jong-Seok Zhang, Jin Rangwala, Reshma A. Lubiniecki, Gregory M. Roach, Charlotte M. Emancipator, Kenneth Gandhi, Leena TI Efficacy of pembrolizumab (MK-3475) and relationship with PD-L1 expression in patients with non-small cell lung cancer: Findings from KEYNOTE-001) SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Garon, Edward B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rizvi, Naiyer] Columbia Univ, New York, NY USA. [Hui, Rina] Univ Sydney, Westmead Hosp, Westmead, NSW 2145, Australia. [Leighl, Natasha B.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Balmanoukian, Ani S.] Angeles Clin & Res Inst, Los Angeles, CA USA. [Eder, Joseph P.] Yale Univ, Ctr Canc, New Haven, CT USA. [Patnaik, Amita] START, San Antonio, TX USA. [Aggarwal, Charu] Univ Penn, Philadelphia, PA 19104 USA. [Gubens, Matthew A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Carcereny, Enric] Catalan Inst Oncol Badalona, Badalona, Spain. [Ahn, Myung-Ju] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Felip, Enriqueta] Vall Hebron Univ Hosp, Barcelona, Spain. [Lee, Jong-Seok] Seoul Natl Univ, Bundang Hosp, Seoul, South Korea. [Zhang, Jin; Rangwala, Reshma A.; Lubiniecki, Gregory M.; Emancipator, Kenneth] Merck & Co Inc, Kenilworth, NJ USA. [Roach, Charlotte M.] Dako, Carpinteria, CA USA. [Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Zhang, Jin/E-8298-2017 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT104 DI 10.1158/1538-7445.AM2015-CT104 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100004 ER PT J AU Germann, U Furey, B Roix, J Markland, W Hoover, R Aronov, A Hale, M Chen, GJ Martinez-Botella, G Alargova, R Fan, B Sorrell, D Meshaw, K Shapiro, P Wick, MJ Benes, C Garnett, M DeCrescenzo, G Namchuk, M Saha, S Welsch, DJ AF Germann, Ursula Furey, Brinley Roix, Jeff Markland, William Hoover, Russell Aronov, Alex Hale, Michael Chen, Guanjing Martinez-Botella, Gabriel Alargova, Rossitza Fan, Bin Sorrell, David Meshaw, Kay Shapiro, Paul Wick, Michael J. Benes, Cyril Garnett, Mathew DeCrescenzo, Gary Namchuk, Mark Saha, Saurabh Welsch, Dean J. TI The selective ERK inhibitor BVD-523 is active in models of MAPK pathway-dependent cancers, including those with intrinsic and acquired drug resistance SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Germann, Ursula] OnKognos Sci Consulting & Serv, Boston, MA USA. [Furey, Brinley; Markland, William; Hoover, Russell; Aronov, Alex; Namchuk, Mark] Vertex Pharmaceut, Boston, MA USA. [Roix, Jeff; DeCrescenzo, Gary; Saha, Saurabh; Welsch, Dean J.] BioMed Valley Discoveries, Kansas City, MO USA. [Hale, Michael] AstraZeneca, Boston, MA USA. [Chen, Guanjing] Novartis, Boston, MA USA. [Martinez-Botella, Gabriel] Sage Therapeut, Boston, MA USA. [Alargova, Rossitza] Blend Therapeut, Boston, MA USA. [Fan, Bin] AVEO Pharmaceut, Boston, MA USA. [Sorrell, David] Horizon Discovery Plc, Cambridge, England. [Meshaw, Kay] Charles River Discovery Res Serv, Chapel Hill, NC USA. [Shapiro, Paul] Univ Maryland, Baltimore, MD 21201 USA. [Wick, Michael J.] South Texas Accelerated Res Therapeut, Austin, TX USA. [Benes, Cyril] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Garnett, Mathew] Wellcome Trust Sanger Inst, Hinxton, England. NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4693 DI 10.1158/1538-7445.AM2015-4693 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104321 ER PT J AU Gjini, E Mansour, M Sander, J He, SN Ko, M Zhou, Y Rodig, S Joung, K Zon, L Rao, A Look, T AF Gjini, Evisa Mansour, Marc Sander, Jeffry He, Shuning Ko, Myunggon Zhou, Yi Rodig, Scott Joung, Keith Zon, Leonard Rao, Anjana Look, Thomas TI Zebrafish models of myeloid malignancies produced through tet2 and asxl1 genomic editing SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Gjini, Evisa; Mansour, Marc; He, Shuning; Look, Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sander, Jeffry] Harvard Univ, Sch Med, Boston, MA USA. [Ko, Myunggon; Rao, Anjana] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Zhou, Yi; Zon, Leonard] Childrens Hosp, Boston, MA 02115 USA. [Rodig, Scott] Brigham & Womens Hosp, Boston, MA 02115 USA. [Joung, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 5152 DI 10.1158/1538-7445.AM2015-5152 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105330 ER PT J AU Gkotzamanidou, M Shammas, M Sanchez, JM Samur, MK Minvielle, S Magrangeas, F Avet-Loiseau, H Dimopoulos, AM Anderson, KC Munshi, NC AF Gkotzamanidou, Maria Shammas, Masood Sanchez, Jesus Martin Samur, Mehmet Kemal Minvielle, Stephane Magrangeas, Florence Avet-Loiseau, Herve Dimopoulos, Athanasios-Meletios Anderson, Kenneth C. Munshi, Nikhil C. TI HDAC8 is recruited to DNA double strand breaks sites and affects the homologous recombination efficiency in multiple myeloma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Gkotzamanidou, Maria; Sanchez, Jesus Martin; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shammas, Masood; Munshi, Nikhil C.] Boston VA Healthcare Syst, Dana Farber Canc Inst, Boston, MA USA. [Samur, Mehmet Kemal] Dept Biostat & Computat Biol, Boston, MA USA. [Minvielle, Stephane; Magrangeas, Florence] CHU Nantes, IRCNA, Hematol Lab, F-44035 Nantes 01, France. [Avet-Loiseau, Herve] Univ Hosp Toulouse, Unit Genom Myeloma, Toulouse, France. [Dimopoulos, Athanasios-Meletios] Univ Athens, Dept Clin Therapeut, Athens, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3035 DI 10.1158/1538-7445.AM2015-3035 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597101084 ER PT J AU Hacohen, N AF Hacohen, Nir TI Genetics of immune escape SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Hacohen, Nir] Broad Inst, Cambridge, MA USA. [Hacohen, Nir] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA SY11-04 DI 10.1158/1538-7445.AM2015-SY11-04 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100427 ER PT J AU Huang, XG Jayabalan, D Di Liberto, M Mark, TM Chen, ZM Rossi, A Schinzel, AC Hahn, WC Hussein, MA Niesvizky, R Chen-Kiang, S AF Huang, Xiangao Jayabalan, David Di Liberto, Maurizio Mark, Tomer M. Chen, Zhengming Rossi, Adriana Schinzel, Anna C. Hahn, William C. Hussein, Mohamad A. Niesvizky, Rubin Chen-Kiang, Selina TI CDK4/6 inhibition amplifies IMiD killing of myeloma cells by accelerating CRL4CRBN-dependent degradation of IKZF1 and IKZF3 in opposition to MEIS2 SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Huang, Xiangao; Jayabalan, David; Di Liberto, Maurizio; Mark, Tomer M.; Chen, Zhengming; Rossi, Adriana; Niesvizky, Rubin; Chen-Kiang, Selina] Weill Cornell Med Coll, New York, NY USA. [Schinzel, Anna C.; Hahn, William C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hussein, Mohamad A.] Celgene Corp, Summit, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4031 DI 10.1158/1538-7445.AM2015-4031 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597103124 ER PT J AU Ignatius, M Lobbardi, R Hayes, M Chen, E McCarthy, K Nielsen, GP Beleyea, B Linardic, C Khan, J Keller, C Langenau, DM AF Ignatius, Myron Lobbardi, Riadh Hayes, Madeline Chen, Eleanor McCarthy, Karin Nielsen, G. Petur Beleyea, Brian Linardic, Corinne Khan, Javed Keller, Charles Langenau, David M. TI Notch signaling increases the number of relapse-driving tumor propagating cells in embryonal rhabdomyosarcoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Ignatius, Myron; Lobbardi, Riadh; Hayes, Madeline; Chen, Eleanor; McCarthy, Karin; Nielsen, G. Petur; Langenau, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Beleyea, Brian; Linardic, Corinne] Duke Univ, Dept Pharmacol & Canc Biol, Med Ctr, Durham, NC USA. [Khan, Javed] NCI, Oncogen Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Keller, Charles] Oregon Hlth & Sci Univ, Dept Pediat, Pape Family Pediat Res Inst, Pediat Canc Biol Program, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4733 DI 10.1158/1538-7445.AM2015-4733 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104360 ER PT J AU Jena, N Joshi, I Yoshida, T Zhang, ZH Liu, ZY Tata, P Shapiro, IM Pachter, JA Weaver, DT Georgopoulos, K Van Etten, RA AF Jena, Nilamani Joshi, Ila Yoshida, Toshimi Zhang, Zhihong Liu, Zhong-Ying Tata, Prasanthi Shapiro, Irina M. Pachter, Jonathan A. Weaver, David T. Georgopoulos, Katia Van Etten, Richard A. TI Targeting focal adhesion kinase is a novel approach to therapy of high-risk, Ikaros-mutant acute B-cell lymphoblastic leukemia SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Jena, Nilamani; Liu, Zhong-Ying; Tata, Prasanthi; Van Etten, Richard A.] Univ Calif Irvine, Irvine, CA USA. [Joshi, Ila; Yoshida, Toshimi; Zhang, Zhihong; Georgopoulos, Katia] Massachusetts Gen Hosp, Cambridge, MA USA. [Shapiro, Irina M.; Pachter, Jonathan A.; Weaver, David T.] Verastem Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4202 DI 10.1158/1538-7445.AM2015-4202 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597103287 ER PT J AU Jia, YH Manning, AD Joshi, RA Fendler, BJ Shivdasani, P Chung, LP Davineni, PK Gong, X Ducar, MD Sholl, LM Lindeman, NI Macconaill, LE Garcia, EP AF Jia, Yonghui Manning, Allison D. Joshi, Ruchi A. Fendler, Bernard J. Shivdasani, Priyanka Chung, Lawrence P. Davineni, Phani K. Gong, Xin Ducar, Matthew D. Sholl, Lynette M. Lindeman, Neal I. Macconaill, Laura E. Garcia, Elizabeth P. TI Reducing GC bias and increasing complexity: Clinical implementation and validation of KAPA library preparation protocol for Oncopanel, a targeted next generation sequencing panel SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Jia, Yonghui; Manning, Allison D.; Joshi, Ruchi A.; Fendler, Bernard J.; Shivdasani, Priyanka; Chung, Lawrence P.; Davineni, Phani K.; Gong, Xin; Sholl, Lynette M.; Lindeman, Neal I.; Garcia, Elizabeth P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ducar, Matthew D.; Macconaill, Laura E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4257 DI 10.1158/1538-7445.AM2015-4257 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597103341 ER PT J AU Katayama, R Yanagitani, N Koike, S Sakashita, T Kitazono, S Nishio, M Okuno, Y Engelman, JA Shaw, AT Fujita, N AF Katayama, Ryohei Yanagitani, Noriko Koike, Sumie Sakashita, Takuya Kitazono, Satoru Nishio, Makoto Okuno, Yasushi Engelman, Jeffrey A. Shaw, Alice T. Fujita, Naoya TI Resistance mechanisms to ALK inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Katayama, Ryohei; Yanagitani, Noriko; Koike, Sumie; Sakashita, Takuya; Kitazono, Satoru; Nishio, Makoto; Fujita, Naoya] Japanese Fdn Canc Res, Tokyo, Japan. [Okuno, Yasushi] Kyoto Univ, Grad Sch Med, Kyoto, Japan. [Engelman, Jeffrey A.; Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3590 DI 10.1158/1538-7445.AM2015-3590 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597102130 ER PT J AU Kelly, RS Sinnott, JA Rider, JR Ebot, E Gerke, T Penney, K Bowden, M Loda, M Kantoff, PW Martin, NE Giovannucci, EL Pettersson, AP Tyekucheva, S Wilson, KM Heiden, MV Mucci, LA AF Kelly, Rachel S. Sinnott, Jennifer A. Rider, Jennifer R. Ebot, Ericka Gerke, Travis Penney, Kathryn Bowden, Michaela Loda, Massimo Kantoff, Philip W. Martin, Neil E. Giovannucci, Edward L. Pettersson, Andreas Pettersson Tyekucheva, Svitlana Wilson, Kathryn M. Heiden, Matthew Vander Mucci, Lorelei A. TI Tumor metabolism as a driver of lethal prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Kelly, Rachel S.; Sinnott, Jennifer A.; Rider, Jennifer R.; Ebot, Ericka; Gerke, Travis; Penney, Kathryn; Giovannucci, Edward L.; Pettersson, Andreas Pettersson; Wilson, Kathryn M.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bowden, Michaela; Loda, Massimo; Kantoff, Philip W.; Martin, Neil E.; Tyekucheva, Svitlana] Dana Farber Canc Inst, Boston, MA 02115 USA. [Heiden, Matthew Vander] MIT, Koch Inst Integrat Canc Res, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 5168 DI 10.1158/1538-7445.AM2015-5168 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105343 ER PT J AU Kote-Jarai, Z Al Olama, AA Dadaev, T Hazelett, D Li, QY Leongamornlert, D Saunders, E Feedman, M Conti, D Easton, D Coetzee, G Eeles, R AF Kote-Jarai, Zsofia Al Olama, Ali Amin Dadaev, Tokhir Hazelett, Dennis Li, Qiuyan Leongamornlert, Daniel Saunders, Ed Feedman, Matthew Conti, David Easton, Douglas Coetzee, Gerhard Eeles, Rosalind CA PRACTICAL Consortium TI Fine mapping of 64 prostate cancer GWAS regions identifies multiple novel association signals SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Kote-Jarai, Zsofia; Dadaev, Tokhir; Leongamornlert, Daniel; Saunders, Ed; Eeles, Rosalind] Inst Canc Res, London SW3 6JB, England. [Al Olama, Ali Amin; Easton, Douglas] Univ Cambridge, Cambridge, England. [Hazelett, Dennis; Conti, David; Coetzee, Gerhard] Keck Sch Med USC, Los Angeles, CA USA. [Li, Qiuyan; Feedman, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4606 DI 10.1158/1538-7445.AM2015-4606 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104234 ER PT J AU Leonard, MK Novak, M Yang, XW Belkin, A Kaetzel, D AF Leonard, M. Kathryn Novak, Marian Yang, Xiuwei Belkin, Alexey Kaetzel, David TI NME1 mediates a switch in expression of beta integrin subunits that correlates with prolonged patient survival SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Leonard, M. Kathryn; Belkin, Alexey; Kaetzel, David] Univ Maryland, Baltimore, MD 21201 USA. [Novak, Marian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yang, Xiuwei] Univ Kentucky, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3257 DI 10.1158/1538-7445.AM2015-3257 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597101286 ER PT J AU Letai, AG AF Letai, Anthony G. TI Conventional chemotherapy cures people by exploiting apoptotic priming SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Letai, Anthony G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA SY20- 01 DI 10.1158/1538-7445.AM2015-SY20-01 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597101008 ER PT J AU Leung, CS Yeung, TL Yip, KP Wong, KK Sood, AK Birrer, MJ Mok, SC AF Leung, Cecilia S. Yeung, Tsz-Lun Yip, Kay-Pong Wong, Kwong-Kwok Sood, Anil K. Birrer, Michael J. Mok, Samuel C. TI CAF-derived MFAP5 promotes tumor angiogenesis and confers paclitaxel resistance in high-grade serous ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Leung, Cecilia S.; Yeung, Tsz-Lun; Wong, Kwong-Kwok; Sood, Anil K.; Mok, Samuel C.] UT MD Anderson Canc Ctr, Houston, TX USA. [Yip, Kay-Pong] Univ S Florida, Tampa, FL USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4184 DI 10.1158/1538-7445.AM2015-4184 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597103271 ER PT J AU Li, YQ Beckman, K Caberto, C Kazma, R Lum-Jones, A Haiman, CA Le Marchand, L Stram, DO Saxena, R Cheng, I AF Li, Yuqing Beckman, Kenneth Caberto, Christian Kazma, Remi Lum-Jones, Annette Haiman, Christopher A. Le Marchand, Loic Stram, Daniel O. Saxena, Richa Cheng, Iona TI Association of genes, pathways, and haplogroups of the mitochondrial genome with the risk of colorectal cancer: The Multiethnic Cohort SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Li, Yuqing; Cheng, Iona] Canc Prevent Inst Calif, Fremont, CA USA. [Beckman, Kenneth] Univ Minnesota, Genom Ctr, Minneapolis, MN USA. [Caberto, Christian; Lum-Jones, Annette; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. [Kazma, Remi] CEA, Ctr Natl Genotypage, Evry, France. [Haiman, Christopher A.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Saxena, Richa] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4589 DI 10.1158/1538-7445.AM2015-4589 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104218 ER PT J AU Lindstrom, S Finucane, H Bulik-Sullivan, B Schumacher, F Amos, C Gruber, S Henderson, B Hunter, D Sellers, T Neale, B Price, A Kraft, P AF Lindstrom, Sara Finucane, Hilary Bulik-Sullivan, Brendan Schumacher, Fredrick Amos, Christopher Gruber, Stephen Henderson, Brian Hunter, David Sellers, Thomas Neale, Benjamin Price, Alkes Kraft, Peter CA GAME-ON Consortium TI Quantification and functional characterization of the shared heritability across multiple cancer sites: results from the GAME-ON Consortium SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Lindstrom, Sara; Finucane, Hilary; Hunter, David; Price, Alkes; Kraft, Peter] Harvard Univ, Boston, MA 02115 USA. [Bulik-Sullivan, Brendan; Neale, Benjamin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schumacher, Fredrick; Gruber, Stephen; Henderson, Brian] Univ So Calif, Los Angeles, CA USA. [Amos, Christopher] Dartmouth Coll, Lebanon, NH USA. [Sellers, Thomas] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4611 DI 10.1158/1538-7445.AM2015-4611 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104239 ER PT J AU Lobbardi, R Pinder, J Martinez, B Blackburn, J Abdelfattah, N Toiber, D De Waard, M Jain, E Sadreyev, R Asara, J Mostoslaysky, R Dellaire, G Langenau, DM AF Lobbardi, Riadh Pinder, Jordan Martinez, Barbara Blackburn, Jessica Abdelfattah, Nouran Toiber, Debra De Waard, Manon Jain, Esha Sadreyev, Ruslan Asara, John Mostoslaysky, Raul Dellaire, Graham Langenau, David M. TI Thymocyte selection-associated HMG box protein (TOX) induces genomic instability in T-cell acute lymphoblastic leukemia SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Lobbardi, Riadh; Martinez, Barbara; Blackburn, Jessica; Abdelfattah, Nouran; Jain, Esha; Sadreyev, Ruslan; Mostoslaysky, Raul; Langenau, David M.] Massachusetts Gen Hosp, Charlestown, MA USA. [Pinder, Jordan; Dellaire, Graham] Beatrice Hunter Canc Res Inst, Halifax, NS, Canada. [Toiber, Debra] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel. [De Waard, Manon] Leiden Univ, Leiden, Netherlands. [Asara, John] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. [Asara, John] Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3865 DI 10.1158/1538-7445.AM2015-3865 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597102389 ER PT J AU LoRusso, P Krop, I Miller, K Ma, C Siegel, BA Shields, AF Molnar, I Wickham, T Reynolds, J Campbell, K Hendriks, B McClure, T Moyo, V Munster, P AF LoRusso, Patricia Krop, Ian Miller, Kathy Ma, Cynthia Siegel, Barry A. Shields, Anthony F. Molnar, Istvan Wickham, Thomas Reynolds, Joseph Campbell, Karen Hendriks, Bart McClure, Ty Moyo, Victor Munster, Pamela TI A phase I study of MM-302, a HER2-targeted PEGylated liposomal doxorubicin, in patients with HER2+metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [LoRusso, Patricia] Yale, New Haven, CT USA. [Krop, Ian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miller, Kathy] Indiana Univ, Indianapolis, IN 46204 USA. [Ma, Cynthia; Siegel, Barry A.] Washington Univ, St Louis, MO USA. [Shields, Anthony F.] Karmanos, Detroit, MI USA. [Molnar, Istvan; Wickham, Thomas; Reynolds, Joseph; Campbell, Karen; Hendriks, Bart; McClure, Ty; Moyo, Victor] Merrimack Pharmaceut, Cambridge, MA USA. [Munster, Pamela] UCSF, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 3 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT234 DI 10.1158/1538-7445.AM2015-CT234 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100068 ER PT J AU LoRusso, PM Tolaney, SM Wong, S Parchment, RE Kinders, RJ Wang, LH Aldrich, J Chen, A Durecki, D Boerner, SA Guthrie, T Bowditch, A Heilbrun, LK Pilat, MJ Craig, D Cai, DP Bell, T Carpten, J Shapiro, G AF LoRusso, Patricia M. Tolaney, Sara M. Wong, Shukmei Parchment, Ralph E. Kinders, Robert J. Wang, Lihua Aldrich, Jessica Chen, Alice Durecki, Diane Boerner, Scott A. Guthrie, Tina Bowditch, Adam Heilbrun, Lance K. Pilat, Mary Jo Craig, David Cai, Dongpo Bell, Tracy Carpten, John Shapiro, Geoffrey TI Combination of the PARP inhibitor veliparib (ABT888) with irinotecan in patients with triple negative breast cancer: Preliminary activity and signature of response SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [LoRusso, Patricia M.; Durecki, Diane; Boerner, Scott A.] Yale Canc Ctr, New Haven, CT USA. [Tolaney, Sara M.; Cai, Dongpo; Bell, Tracy; Shapiro, Geoffrey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wong, Shukmei; Aldrich, Jessica; Craig, David; Carpten, John] Translat Genom Res Inst, Phoenix, AZ USA. [Parchment, Ralph E.; Kinders, Robert J.; Wang, Lihua] Frederick Natl Lab Canc Res, Frederick, MD USA. [Chen, Alice] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Guthrie, Tina; Bowditch, Adam; Heilbrun, Lance K.] Karmanos Canc Inst, Detroit, MI USA. [Pilat, Mary Jo] Wayne State Univ, Detroit, MI USA. NR 0 TC 3 Z9 3 U1 4 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT325 DI 10.1158/1538-7445.AM2015-CT325 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100097 ER PT J AU Lugovskoy, AA Curley, M Baum, J Adams, S Ladevaia, S Rimkunas, V Camblin, A Nie, L Tan, G Johnson, B Mathews, S Horgan, K Louis, CU Czibere, AG Arnedos, M Soria, JC Bahleda, R Shields, A LoRusso, PM Saleh, M Isakoff, SJ AF Lugovskoy, Alexey A. Curley, Michel Baum, Jason Adams, Sharlene Ladevaia, Sergio Rimkunas, Victoria Camblin, Adam Nie, Lin Tan, Gege Johnson, Bryan Mathews, Sara Horgan, Kerry Louis, Chrystal U. Czibere, Akos G. Arnedos, Monica Soria, Jean-Charles Bahleda, Rastilav Shields, Anthony LoRusso, Patricia M. Saleh, Mansoor Isakoff, Steven J. TI Preclinical characterization and first-in-human study of MM-141, a dual antibody inhibitor of IGF-1R and ErbB3 SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Lugovskoy, Alexey A.; Curley, Michel; Baum, Jason; Adams, Sharlene; Ladevaia, Sergio; Rimkunas, Victoria; Camblin, Adam; Nie, Lin; Tan, Gege; Johnson, Bryan; Mathews, Sara; Horgan, Kerry; Louis, Chrystal U.; Czibere, Akos G.] Merrimack Pharmaceut Inc, Cambridge, MA USA. [Arnedos, Monica; Soria, Jean-Charles; Bahleda, Rastilav] Inst Gustav Roussy, Villejuif, France. [Shields, Anthony; LoRusso, Patricia M.] Karmanos Canc Inst, Detroit, MI USA. [Saleh, Mansoor] Northside Hosp, Inst Canc, Georgia Canc Specialists, Atlanta, GA USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT237 DI 10.1158/1538-7445.AM2015-CT237 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100070 ER PT J AU Matulonis, UA Wulf, G Barry, W Birrer, M Westin, S Spagnoletti, T Bell-McGuinn, K Obermayer, E Whalen, C Aghajanian, C Solit, D Mills, G Cantley, L Winer, E AF Matulonis, Ursula A. Wulf, Gerburg Barry, William Birrer, Michael Westin, Shannon Spagnoletti, Tatum Bell-McGuinn, Katherine Obermayer, Elizabeth Whalen, Christin Aghajanian, Carol Solit, David Mills, Gordon Cantley, Lewis Winer, Eric TI Phase I of oral BKM120 or BYL719 and olaparib for high-grade serous ovarian cancer or triple-negative breast cancer: Final results of the BKM120 plus olaparib cohort SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Matulonis, Ursula A.; Barry, William; Spagnoletti, Tatum; Obermayer, Elizabeth; Whalen, Christin; Winer, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wulf, Gerburg] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Birrer, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Westin, Shannon; Mills, Gordon] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bell-McGuinn, Katherine; Aghajanian, Carol; Solit, David] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Cantley, Lewis] Cornell Weill Med Coll, New York, NY USA. NR 0 TC 1 Z9 1 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT324 DI 10.1158/1538-7445.AM2015-CT324 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100096 ER PT J AU Mayer, IA Abramson, V Balko, J Sanders, M Juric, D Solit, D Li, YS Cantley, L Winer, E Arteaga, C AF Mayer, Ingrid A. Abramson, Vandana Balko, Justin Sanders, Melinda Juric, Dejan Solit, David Li, Yisheng Cantley, Lewis Winer, Eric Arteaga, Carlos TI SU2C Phase Ib study of the PI3K-alpha inhibitor BYL719 (alpelisib) with letrozole in ER+/HER2-metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Mayer, Ingrid A.; Abramson, Vandana; Balko, Justin; Sanders, Melinda; Arteaga, Carlos] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Juric, Dejan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Solit, David] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Li, Yisheng] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cantley, Lewis] Weill Cornell Med Coll, New York, NY USA. [Winer, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT232 DI 10.1158/1538-7445.AM2015-CT232 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100066 ER PT J AU Middleton, RE Olsen, G McSweeney, R Lu, G Gao, WH Roberts, J McKeown, MR Bittinger, MA Wong, KK Bradner, JE Kaelin, WG AF Middleton, Richard E. Olsen, Greg McSweeney, Russell Lu, Gang Gao, Wenhua Roberts, Justin McKeown, Michael R. Bittinger, Mark A. Wong, Kwok-Kin Bradner, James E. Kaelin, William G. TI Targeting oncoproteins via disruption of proteostasis: Identification of oncoprotein destabilizing agents using luciferase tagged oncoproteins SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Middleton, Richard E.; Olsen, Greg; McSweeney, Russell; Lu, Gang; Gao, Wenhua; Roberts, Justin; McKeown, Michael R.; Bittinger, Mark A.; Wong, Kwok-Kin; Bradner, James E.; Kaelin, William G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 5436 DI 10.1158/1538-7445.AM2015-5436 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597106095 ER PT J AU Min, L Gao, Y Hornicek, FJ Amiji, MM Duan, ZF AF Min, Lin Gao, Yan Hornicek, Francis J. Amiji, Mansoor M. Duan, Zhenfeng TI Layer-by-layer engineering of upconversion nanoparticle based siRNA and miRNA delivery system for cancer therapy SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Min, Lin; Gao, Yan; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Amiji, Mansoor M.] Northeastern Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 5 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA LB-102 DI 10.1158/1538-7445.AM2015-LB-102 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100205 ER PT J AU Mitsui, Y Hirata, H Arichi, N Hiraki, M Yasumono, H Chang, I Fukuhara, S Yamamura, S Shahryari, V Deng, GR Saini, S Majid, S Tanaka, Y Dahiya, R Shiina, H AF Mitsui, Yozo Hirata, Hiroshi Arichi, Naoko Hiraki, Miho Yasumono, Hiroaki Chang, Inik Fukuhara, Shinichiro Yamamura, Soichiro Shahryari, Varahram Deng, Guoren Saini, Sharanjot Majid, Shahana Tanaka, Yuichiro Dahiya, Rajvir Shiina, Hiroaki TI Dysregulation of bone morphogenetic protein 2 serves as a candidate molecular marker in human renal cell carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Mitsui, Yozo; Hirata, Hiroshi; Yamamura, Soichiro; Shahryari, Varahram; Deng, Guoren; Saini, Sharanjot; Majid, Shahana; Tanaka, Yuichiro; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Mitsui, Yozo; Hirata, Hiroshi; Yamamura, Soichiro; Shahryari, Varahram; Deng, Guoren; Saini, Sharanjot; Majid, Shahana; Tanaka, Yuichiro; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Arichi, Naoko; Hiraki, Miho; Yasumono, Hiroaki; Shiina, Hiroaki] Shimane Univ, Fac Med, Dept Urol, Izumo, Shimane, Japan. [Chang, Inik] Yonsei Univ, Dept Oral Biol, Coll Densitry, Seoul 120749, South Korea. [Fukuhara, Shinichiro] Osaka Univ, Grad Sch Med, Dept Urol, Suita, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3823 DI 10.1158/1538-7445.AM2015-3823 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597102351 ER PT J AU Moaven, O Wei, L Harriman, G Greenwood, J Bhat, S Westlin, WF Harwood, HJ Kapeller, R DePeralta, DK Tanabe, KK Fuchs, BC AF Moaven, Omeed Wei, Lan Harriman, Geraldine Greenwood, Jeremy Bhat, Sathesh Westlin, William F. Harwood, H. James Kapeller, Rosana DePeralta, Danielle K. Tanabe, Kenneth K. Fuchs, Bryan C. TI Liver selective acetyl-CoA carboxylase inhibition by ND-654 improves survival in cirrhotic rats with hepatocellular carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Moaven, Omeed; Wei, Lan; DePeralta, Danielle K.; Tanabe, Kenneth K.; Fuchs, Bryan C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harriman, Geraldine; Westlin, William F.; Harwood, H. James; Kapeller, Rosana] Nimbus Discovery, Cambridge, MA USA. [Harriman, Geraldine; Greenwood, Jeremy] Schrodinger, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4452 DI 10.1158/1538-7445.AM2015-4452 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104080 ER PT J AU Nicolas-Metral, V Vaslin, A Supko, JG Nakai, K Ishii, N Menetrey, A Roubaudi-Fraschini, MC Marfurt, J Chabaud, S Layer, A Purcea, D Douchain, J Zanna, C AF Nicolas-Metral, Valerie Vaslin, Anne Supko, Jeffrey G. Nakai, Kiyohiko Ishii, Nobuya Menetrey, Annick Roubaudi-Fraschini, Marie-Claude Marfurt, Judith Chabaud, Sebastien Layer, Andreas Purcea, Daniela Douchain, Jerome Zanna, Claudio TI Formulation switch and pharmacokinetics/pharmacodynamics of Debio 1347 (CH5183284), a novel FGFR inhibitor, in a first-in-human dose escalation trial in solid tumors patients SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Nicolas-Metral, Valerie; Vaslin, Anne; Menetrey, Annick; Roubaudi-Fraschini, Marie-Claude; Marfurt, Judith; Chabaud, Sebastien; Layer, Andreas; Purcea, Daniela; Douchain, Jerome; Zanna, Claudio] Debiopharm Int SA, Lausanne, Switzerland. [Supko, Jeffrey G.] Massachusetts Gen Hosp, Clin Pharmacol Lab, Boston, MA 02114 USA. [Nakai, Kiyohiko; Ishii, Nobuya] Chugai Pharmaceut Co Ltd, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT228 DI 10.1158/1538-7445.AM2015-CT228 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100062 ER PT J AU Ning, JF Wakimoto, H Martuza, R Rabkin, S AF Ning, Jianfang Wakimoto, Hiroaki Martuza, Robert Rabkin, Samuel TI PARP inhibitors sensitize glioblastoma stem cells to oncolytic herpes simplex virus therapy SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Ning, Jianfang; Wakimoto, Hiroaki; Martuza, Robert; Rabkin, Samuel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4227 DI 10.1158/1538-7445.AM2015-4227 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597103311 ER PT J AU Nissim, S Weeks, O Hedgepeth, J Wucherpfennig, J Wang, XX Kimmelman, A Goessling, W AF Nissim, Sahar Weeks, Olivia Hedgepeth, John Wucherpfennig, Julia Wang, Xiao-Xu Kimmelman, Alec Goessling, Wolfram TI NR5A2 is essential for pancreas development and affects pancreas carcinogenesis SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Nissim, Sahar; Weeks, Olivia; Hedgepeth, John; Wucherpfennig, Julia] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wang, Xiao-Xu; Kimmelman, Alec] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goessling, Wolfram] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 5148 DI 10.1158/1538-7445.AM2015-5148 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105326 ER PT J AU Obholzer, ND Haas, BJ Landau, DA Pochet, N Regev, A Wu, C AF Obholzer, Nikolaus D. Haas, Brian J. Landau, Dan-Avi Pochet, Nathalie Regev, Aviv Wu, Catherine TI Development of a cancer transcriptome analysis toolkit: identification of gene fusions in chronic lymphocytic leukemia SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Obholzer, Nikolaus D.; Pochet, Nathalie] Brigham & Womens Hosp, Boston, MA 02115 USA. [Haas, Brian J.; Landau, Dan-Avi; Regev, Aviv] Broad Inst, Boston, MA USA. [Wu, Catherine] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4859 DI 10.1158/1538-7445.AM2015-4859 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105044 ER PT J AU Olar, A Wani, K Diefes, K Heathcock, L van Thuijl, H Gilbert, M Armstrong, T Sulman, E Cahill, D Reijneveld, J Ylstra, B Wesseling, P Aldape, K AF Olar, Adriana Wani, Khalida Diefes, Kristin Heathcock, Lindsey van Thuijl, Hinke Gilbert, Mark Armstrong, Terri Sulman, Erik Cahill, Daniel Reijneveld, Jaap Ylstra, Bauke Wesseling, Pieter Aldape, Kenneth TI IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Olar, Adriana; Wani, Khalida; Diefes, Kristin; Heathcock, Lindsey; Gilbert, Mark; Armstrong, Terri; Sulman, Erik] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [van Thuijl, Hinke; Reijneveld, Jaap; Ylstra, Bauke; Wesseling, Pieter] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Cahill, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Aldape, Kenneth] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Aldape, Kenneth] Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. RI Ylstra, Bauke/D-2906-2012 OI Ylstra, Bauke/0000-0001-9479-3010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 5270 DI 10.1158/1538-7445.AM2015-5270 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105437 ER PT J AU Oxnard, GR Thress, KS Paweletz, CP Felip, E Cho, BC Stetson, D Dougherty, B Lai, ZW Morkovets, A Vivancos, A Kuang, YN Ercan, D Cantarini, M Barret, JC Janne, PA AF Oxnard, Geoffrey R. Thress, Kenneth S. Paweletz, Cloud P. Felip, Enriqueta Cho, Byoung Chul Stetson, Daniel Dougherty, Brian Lai, Zhongwu Morkovets, Aleksandra Vivancos, Ana Kuang, Yanan Ercan, Dalia Cantarini, Mireille Barret, J. Carl Janne, Pasi A. TI Analysis of cell-free plasma DNA (cfDNA) identifies 3 molecular subtypes of acquired resistance to AZD9291, a novel EGFR tyrosine kinase inhibitor (TKI), in patients (pts) with advanced lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Oxnard, Geoffrey R.; Paweletz, Cloud P.; Kuang, Yanan; Ercan, Dalia; Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Thress, Kenneth S.; Stetson, Daniel; Dougherty, Brian; Lai, Zhongwu; Morkovets, Aleksandra; Barret, J. Carl] AstraZeneca, Waltham, MA USA. [Felip, Enriqueta; Vivancos, Ana] Vall D Hebron Inst Oncol, Barceloma, Spain. [Cho, Byoung Chul] Yonsei Canc Ctr, Seoul, South Korea. [Cantarini, Mireille] AstraZeneca, Macclesfield, Cheshire, England. NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA LB-123 DI 10.1158/1538-7445.AM2015-LB-123 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100225 ER PT J AU Paoluzzi, L Hanniford, D Sokoova, E Osman, M Darvishian, F Wang, JH Bradner, JE Hernando, E AF Paoluzzi, Luca Hanniford, Douglas Sokoova, Elena Osman, Man Darvishian, Farbod Wang, Jinhua Bradner, James E. Hernando, Eva TI BET and BRAF inhibitors act synergistically against BRAF mutant melanoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Paoluzzi, Luca; Hanniford, Douglas; Sokoova, Elena; Osman, Man; Darvishian, Farbod; Wang, Jinhua; Hernando, Eva] NYU, New York, NY USA. [Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3522 DI 10.1158/1538-7445.AM2015-3522 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597102063 ER PT J AU Patel, JM Noble, PW Chan, G Weisbart, RH Hansen, JE AF Patel, Jaymin M. Noble, Phil W. Chan, Grace Weisbart, Richard H. Hansen, James E. TI Engineering a trivalent lupus anti-DNA autoantibody fragment for cancer therapy SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Patel, Jaymin M.; Noble, Phil W.; Hansen, James E.] Yale Univ, Sch Med, New Haven, CT USA. [Chan, Grace; Weisbart, Richard H.] Vet Affairs Greater Los Angeles Hlth Care Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4276 DI 10.1158/1538-7445.AM2015-4276 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597103360 ER PT J AU Perera, RM Stoykova, S Nicolay, BN Ross, KN Fitamant, J Boukhali, M Deshpande, V Selig, MK Ferrone, CR Settleman, J Stephanopoulos, G Dyson, NJ Zoncu, R Ramaswamy, S Haas, W Bardeesy, NM AF Perera, Rushika M. Stoykova, Svetlana Nicolay, Brandon N. Ross, Kenneth N. Fitamant, Julien Boukhali, Myriam Deshpande, Vikram Selig, Martin K. Ferrone, Cristina R. Settleman, Jeff Stephanopoulos, Gregory Dyson, Nicholas J. Zoncu, Roberto Ramaswamy, Sridhar Haas, Wilhelm Bardeesy, Nabeel M. TI Transcriptional mechanisms for autophagy regulation and metabolic reprogramming in pancreatic cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Perera, Rushika M.; Stoykova, Svetlana; Nicolay, Brandon N.; Ross, Kenneth N.; Fitamant, Julien; Boukhali, Myriam; Settleman, Jeff; Dyson, Nicholas J.; Ramaswamy, Sridhar; Haas, Wilhelm; Bardeesy, Nabeel M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Deshpande, Vikram; Selig, Martin K.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stephanopoulos, Gregory] MIT, Cambridge, MA 02139 USA. [Zoncu, Roberto] Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA NG08 DI 10.1158/1538-7445.AM2015-NG08 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100407 ER PT J AU Rand, KA Song, C Dean, E Serie, D Curtin, K Hazelett, D Hwang, AE Sheng, X Stram, A Van Den Berg, DJ Huff, CA Bernal-Mizrachi, L Tomasson, MH Ailawadhi, S De Roos, A Singhal, S Pawlish, K Peters, E Bock, C Conti, DV Colditz, G Zimmerman, T Huntsman, S Graff, J Chanock, SJ Lieber, M Mehta, J Klein, EA Janakiraman, N Severson, RK Brooks-Wilson, AR Rajkumar, V Brown, EE Kolonel, L Slager, S Henderson, BE Giles, GG Spinelli, JJ Chiu, B Anderson, KC Zonder, J Orlowski, RZ Lonial, S Camp, N Vachon, C Ziv, E Stram, DO Haiman, CA Cozen, W AF Rand, Kristin A. Song, Chi Dean, Eric Serie, Daniel Curtin, Karen Hazelett, Dennis Hwang, Arnie E. Sheng, Xin Stram, Alex Van Den Berg, David J. Huff, Carol Ann Bernal-Mizrachi, Leon Tomasson, Michael H. Ailawadhi, Sikander De Roos, Anneclaire Singhal, Seema Pawlish, Karen Peters, Edward Bock, Catherine Conti, David V. Colditz, Graham Zimmerman, Todd Huntsman, Scott Graff, John Chanock, Stephen J. Lieber, Michael Mehta, Jayesh Klein, Eric A. Janakiraman, Nalini Severson, Richard K. Brooks-Wilson, Angela R. Rajkumar, Vincent Brown, Elizabeth E. Kolonel, Laurence Slager, Susan Henderson, Brian E. Giles, Graham G. Spinelli, John J. Chiu, Brian Anderson, Kenneth C. Zonder, Jeffrey Orlowski, Robert Z. Lonial, Sagar Camp, Nicola Vachon, Celine Ziv, Elad Stram, Dan O. Haiman, Christopher A. Cozen, Wendy CA African Ancestry Prostate Canc GWA African Ancestry Breast Canc GWAS TI Multiple myeloma susceptibility loci examined in African and European ancestry populations SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Rand, Kristin A.; Song, Chi; Hazelett, Dennis; Hwang, Arnie E.; Sheng, Xin; Stram, Alex; Van Den Berg, David J.; Conti, David V.; Lieber, Michael; Henderson, Brian E.; Stram, Dan O.; Haiman, Christopher A.; Cozen, Wendy] Keck Sch Med USC, Los Angeles, CA USA. [Rand, Kristin A.; Song, Chi; Hazelett, Dennis; Hwang, Arnie E.; Sheng, Xin; Stram, Alex; Van Den Berg, David J.; Conti, David V.; Lieber, Michael; Henderson, Brian E.; Stram, Dan O.; Haiman, Christopher A.; Cozen, Wendy] Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Dean, Eric; Huntsman, Scott; Ziv, Elad] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Serie, Daniel; Ailawadhi, Sikander] Mayo Clin, Jacksonville, FL 32224 USA. [Curtin, Karen; Camp, Nicola] Univ Utah, Sch Med, Salt Lake City, UT USA. [Huff, Carol Ann] Johns Hopkins Sch Med, Baltimore, MD USA. [Bernal-Mizrachi, Leon; Lonial, Sagar] Emory Univ, Sch Med, Atlanta, GA USA. [Tomasson, Michael H.; Colditz, Graham] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. [De Roos, Anneclaire] Drexel Univ, Philadelphia, PA 19104 USA. [Singhal, Seema; Mehta, Jayesh] Northwestern Univ, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA. [Pawlish, Karen] New Jersey Dept Hlth, New Jersey State Canc Registry, Trenton, NJ USA. [Peters, Edward] Louisiana State Univ, Sch Publ Hlth, New Orleans, LA USA. [Bock, Catherine; Severson, Richard K.; Zonder, Jeffrey] Wayne State Univ Med, Karmanos Canc Inst, Detroit, MI USA. [Zimmerman, Todd; Chiu, Brian] Univ Chicago, Chicago, IL 60637 USA. [Graff, John] Rutgers State Univ, Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Klein, Eric A.] Cleveland Clin, Cleveland, OH 44106 USA. [Janakiraman, Nalini] Henry Ford Hosp, Detroit, MI 48202 USA. [Brooks-Wilson, Angela R.] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada. [Rajkumar, Vincent; Slager, Susan; Vachon, Celine] Mayo Clin, Rochester, MN USA. [Brown, Elizabeth E.] Univ Alabama Birmingham, Birmingham, AL USA. [Kolonel, Laurence] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Giles, Graham G.] Univ Melbourne, Canc Council Victoria, Melbourne, Vic, Australia. [Giles, Graham G.] Monash Univ, Melbourne, Vic 3004, Australia. [Spinelli, John J.] Univ British Columbia, Canc Control Res, Vancouver, BC V5Z 1M9, Canada. [Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Brooks-Wilson, Angela/E-9399-2012 OI Brooks-Wilson, Angela/0000-0003-1009-6408 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4629 DI 10.1158/1538-7445.AM2015-4629 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104257 ER PT J AU Rathkopf, DE Smith, MR Antonarakis, ES Ryan, CJ Berry, WR Shore, ND Liu, G Higano, C Alumkal, JJ Hauke, R Tutrone, R Saleh, M Maneval, EC Thomas, S Ricci, D Yu, MK de Boer, CJ Trinh, A Kheoh, T Bandekar, R Scher, HI AF Rathkopf, Dana E. Smith, Matthew R. Antonarakis, Emmanuel S. Ryan, Charles J. Berry, William R. Shore, Neal D. Liu, Glenn Higano, Celestia Alumkal, Joshi J. Hauke, Ralph Tutrone, Ronald Saleh, Mansoor Maneval, Edna Chow Thomas, Shibu Ricci, Deborah Yu, Margaret K. de Boer, Carla J. Trinh, Angela Kheoh, Thian Bandekar, Rajesh Scher, Howard I. TI Androgen receptor (AR) mutations in patients (pts) with castration-resistant prostate cancer (CRPC) with and without prior abiraterone acetate (AA) treatment SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Rathkopf, Dana E.; Scher, Howard I.] Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10021 USA. [Rathkopf, Dana E.; Scher, Howard I.] Weill Cornell Med Coll, New York, NY USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Matthew R.] Harvard Univ, Sch Med, Boston, MA USA. [Antonarakis, Emmanuel S.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Ryan, Charles J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Berry, William R.] Canc Ctr North Carolina, Raleigh, NC USA. [Shore, Neal D.] Carolina Urol Res Ctr, Myrtle Beach, SC USA. [Liu, Glenn] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Higano, Celestia] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Alumkal, Joshi J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Hauke, Ralph] Nebraska Canc Specialists, Omaha, NE USA. [Tutrone, Ronald] Chesapeake Urol Res Associates, Baltimore, MD USA. [Saleh, Mansoor] Georgia Canc Specialists PC, Sandy Springs, GA USA. [Maneval, Edna Chow] Seragon Pharmaceut, San Diego, CA USA. [Thomas, Shibu; Ricci, Deborah] Janssen Res & Dev, Raritan, NJ USA. [Yu, Margaret K.; Trinh, Angela] Janssen Res & Dev, Los Angeles, CA USA. [de Boer, Carla J.] Janssen Biol BV, Leiden, Netherlands. [Kheoh, Thian] Janssen Res & Dev, San Diego, CA USA. [Bandekar, Rajesh] Janssen Res & Dev, Spring House, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT134 DI 10.1158/1538-7445.AM2015-CT134 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100030 ER PT J AU Rochon, LS Devarakonda, K Martinez, J Williams, K Hamilton, EP Shapiro, G Sukari, A AF Rochon, Louise S. Devarakonda, Krishna Martinez, Jose Williams, Kelly Hamilton, Erika P. Shapiro, Geoffrey Sukari, Ammar TI A phase I first in human dose escalation trial of MNK-010 in subjects with advanced solid tumors SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Rochon, Louise S.; Devarakonda, Krishna; Martinez, Jose; Williams, Kelly] Mallinckrodt Pharmaceut, Hazelwood, MO USA. [Hamilton, Erika P.] Sarah Cannon Res Inst, Nashville, TN USA. [Hamilton, Erika P.] Tennessee Oncol, Nashville, TN USA. [Shapiro, Geoffrey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sukari, Ammar] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT230 DI 10.1158/1538-7445.AM2015-CT230 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100064 ER PT J AU Sarosiek, KA Ziller, M Fraser, C Bhola, P Ryan, J Deng, J Jian, B Goldenberg, M Madsen, J Carrasco, R Robinson, S Moslehi, J Letai, A AF Sarosiek, Kristopher A. Ziller, Michael Fraser, Cameron Bhola, Patrick Ryan, Jeremy Deng, Jing Jian, Brian Goldenberg, Marti Madsen, Joseph Carrasco, Ruben Robinson, Shenandoah Moslehi, Javid Letai, Anthony TI Apoptotic priming is regulated by a developmental program and predisposes children to therapy-induced toxicity SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Sarosiek, Kristopher A.; Fraser, Cameron; Bhola, Patrick; Ryan, Jeremy; Deng, Jing; Carrasco, Ruben; Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ziller, Michael] Broad Inst Harvard & MIT, Cambridge, MA USA. [Jian, Brian] Kaiser Permanente, Sacramento, CA USA. [Goldenberg, Marti; Madsen, Joseph; Robinson, Shenandoah] Boston Childrens Hosp, Boston, MA USA. [Moslehi, Javid] Vanderbilt Univ, Nashville, TN 37235 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4728 DI 10.1158/1538-7445.AM2015-4728 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104356 ER PT J AU Saung, MT Sharei, A Adalsteinsson, V Liss, A Cho, N Kamath, T Ruiz, C Kirkpatrick, J Langer, R Love, C Jensen, K AF Saung, May Tun Sharei, Armon Adalsteinsson, Viktor Liss, Andrew Cho, Nahyun Kamath, Tushar Ruiz, Camilo Kirkpatrick, Jesse Langer, Robert Love, Christopher Jensen, Klavs TI Cell size-specific intracellular delivery SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Saung, May Tun; Liss, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sharei, Armon; Adalsteinsson, Viktor; Cho, Nahyun; Kamath, Tushar; Ruiz, Camilo; Kirkpatrick, Jesse; Langer, Robert; Love, Christopher; Jensen, Klavs] MIT, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 5538A DI 10.1158/1538-7445.AM2015-5538A PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597106197 ER PT J AU Schellens, JHM van Geel, R Bendell, JC Spreafico, A Schuler, M Yoshino, T Delord, JP Yamada, Y Lolkema, MP Faris, JE Eskens, FALM Sharma, S Yaeqer, R Lenz, HJ Wainberg, ZA Avsar, E Chatterjee, A Jaeger, S Demuth, T Tabemero, J AF Schellens, Jan H. M. van Geel, Robin Bendell, Johanna C. Spreafico, Anna Schuler, Martin Yoshino, Takayuki Delord, Jean-Pierre Yamada, Yasuhide Lolkema, Martijn P. Faris, Jason E. Eskens, Ferry A. L. M. Sharma, Sunil Yaeqer, Rona Lenz, Heinz-Josef Wainberg, Zev A. Avsar, Emin Chatterjee, Arkendu Jaeger, Savina Demuth, Tim Tabemero, Josep TI Final biomarker analysis of the phase I study of the selective BRAF V600 inhibitor encorafenib (LGX818) combined with cetuximab with or without the alpha-specific PI3K inhibitor alpelisib (BYL719) in patients with advanced BRAF-mutant colorectal cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Schellens, Jan H. M.; van Geel, Robin] Netherlands Canc Inst, Amsterdam, Netherlands. [Bendell, Johanna C.] Sarah Cannon Res Inst, Nashville, TN USA. [Spreafico, Anna] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Schuler, Martin] Univ Hosp Essen, West German Canc Ctr, Essen, Germany. [Yoshino, Takayuki] Natl Canc Ctr Hosp East, Chiba, Japan. [Delord, Jean-Pierre] Inst Claudius Regaud, Toulouse, France. [Yamada, Yasuhide] Natl Canc Ctr, Tokyo, Japan. [Lolkema, Martijn P.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Faris, Jason E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eskens, Ferry A. L. M.] Erasmus MC Canc Inst, Rotterdam, Netherlands. [Sharma, Sunil] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Yaeqer, Rona] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lenz, Heinz-Josef] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Wainberg, Zev A.] Univ Calif Los Angeles, Med Ctr, Santa Monica, CA USA. [Avsar, Emin; Chatterjee, Arkendu] Novartis Pharmaceut, E Hanover, NJ USA. [Jaeger, Savina] Novartis Inst Biomed Res, Cambridge, MA USA. [Demuth, Tim] Novartis Pharma AG, Basel, Switzerland. [Tabemero, Josep] Vall Hebron Univ Hosp, Barcelona, Spain. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT136 DI 10.1158/1538-7445.AM2015-CT136 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100032 ER PT J AU Schofield, H Bednar, F Collins, M Yan, W Zhang, YQ Shyam, N Eberle, J Olive, K Bardeesy, N Nakada, D Simeone, D Morrison, S di Magliano, MP AF Schofield, Heather Bednar, Filip Collins, Meredith Yan, Wei Zhang, Yaqing Shyam, Nikhil Eberle, Jaime Olive, Kenneth Bardeesy, Nabeel Nakada, Daisuke Simeone, Diane Morrison, Sean di Magliano, Marina Pasca TI Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Schofield, Heather; Bednar, Filip; Collins, Meredith; Zhang, Yaqing; Shyam, Nikhil; Simeone, Diane; di Magliano, Marina Pasca] Univ Michigan, Ann Arbor, MI 48109 USA. [Yan, Wei] Fourth Mil Med Univ, Xian 710032, Peoples R China. [Eberle, Jaime; Olive, Kenneth] Columbia Univ, New York, NY USA. [Bardeesy, Nabeel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nakada, Daisuke] Baylor Coll Med, Houston, TX 77030 USA. [Morrison, Sean] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA LB-061 DI 10.1158/1538-7445.AM2015-LB-061 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100165 ER PT J AU Sconocchia, G Arriga, R Caratelli, S Lanzilli, G Coppola, A Spagnoli, GC Venditti, A Amadori, S Lauro, D Del Principe, MI Maurillo, L Buccisano, F Capuani, B Wang, XH Ferrone, S AF Sconocchia, Giuseppe Arriga, Roberto Caratelli, Sara Lanzilli, Giulia Coppola, Andrea Spagnoli, Giulio C. Venditti, Adriano Amadori, Sergio Lauro, Davide Del Principe, Maria I. Maurillo, Luca Buccisano, Francesco Capuani, Barbara Wang, Xinhui Ferrone, Soldano TI Association of long term NK cell culture and TIMP3 over-expression with NK cell reduced susceptibility to leukemia and epithelial cancer cell induced damage SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Sconocchia, Giuseppe; Caratelli, Sara; Lanzilli, Giulia] Inst Translat Pharmacol, Rome, Italy. [Arriga, Roberto; Coppola, Andrea; Lauro, Davide; Capuani, Barbara] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy. [Spagnoli, Giulio C.] Univ Basel, Inst Surg Res & Hosp Management, Basel, Switzerland. [Venditti, Adriano; Amadori, Sergio; Del Principe, Maria I.; Maurillo, Luca; Buccisano, Francesco] Univ Roma Tor Vergata, Hematol, Rome, Italy. [Wang, Xinhui; Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4050 DI 10.1158/1538-7445.AM2015-4050 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597103143 ER PT J AU Sholl, LM Garcia, E Jia, YH Ducar, M Fendler, B Shivdasani, P Kuo, FC Ligon, AH Rollins, BJ Lindeman, NI MacConaill, LE AF Sholl, Lynette M. Garcia, Elizabeth Jia, Yonghui Ducar, Matthew Fendler, Bernard Shivdasani, Priyanka Kuo, Frank C. Ligon, Azra H. Rollins, Barrett J. Lindeman, Neal I. MacConaill, Laura E. TI Revolutionizing clinical care using prospective, institution-wide tumor sequencing SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Sholl, Lynette M.; Kuo, Frank C.; Ligon, Azra H.; Lindeman, Neal I.; MacConaill, Laura E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Garcia, Elizabeth; Jia, Yonghui; Ducar, Matthew; Fendler, Bernard; Shivdasani, Priyanka; Rollins, Barrett J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4666 DI 10.1158/1538-7445.AM2015-4666 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104294 ER PT J AU Sotayo, AO Guerriero, JL Ponichtera, HE Letai, AG AF Sotayo, Alaba O. Guerriero, Jennnifer L. Ponichtera, Holly E. Letai, Anthony G. TI Polarizing tumor associated macrophages (TAMs) towards an anti-tumor phenotype with a novel compound reveals a new subset of TAMs within breast tumors which facilitate tumor regression SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Sotayo, Alaba O.; Guerriero, Jennnifer L.; Ponichtera, Holly E.; Letai, Anthony G.] Dana Farber Canc Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 5030 DI 10.1158/1538-7445.AM2015-5030 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105210 ER PT J AU Starodub, AN Ocean, AJ Bardia, A Guarino, MJ Messersmith, W Berlin, J Picozzi, VJ Thomas, SS Masters, G Vandat, LT Mayer, IA Moroose, R Diamond, JS Tagawa, ST Shah, MA Wilhelm, F Wegener, WA Maliakal, P Sharkey, RM Goldenberg, DM AF Starodub, Alexander N. Ocean, Allyson J. Bardia, Aditya Guarino, Michael J. Messersmith, Wells Berlin, Jordan Picozzi, Vincent J. Thomas, Sajeve S. Masters, Gregory Vandat, Linda T. Mayer, Ingrid A. Moroose, Rebecca Diamond, Jennifer S. Tagawa, Scott T. Shah, Manish A. Wilhelm, Francois Wegener, William A. Maliakal, Pius Sharkey, Robert M. Goldenberg, David M. TI Advanced solid cancer therapy with a novel antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): key preclinical and clinical results SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Starodub, Alexander N.] Indiana Univ, Hlth Ctr Canc Care, Goshen, IN USA. [Ocean, Allyson J.; Vandat, Linda T.; Tagawa, Scott T.; Shah, Manish A.] Weill Cornell Med Coll, New York, NY USA. [Bardia, Aditya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Guarino, Michael J.; Masters, Gregory] Helen F Graham Canc Ctr, Newark, DE USA. [Messersmith, Wells; Diamond, Jennifer S.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Berlin, Jordan; Mayer, Ingrid A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Picozzi, Vincent J.] Virginia Mason Canc Ctr, Seattle, WA USA. [Thomas, Sajeve S.; Moroose, Rebecca] Univ Florida, Hlth Canc Ctr, Orlando, FL USA. [Wilhelm, Francois; Wegener, William A.; Maliakal, Pius; Sharkey, Robert M.; Goldenberg, David M.] Immunomedics Inc, Morris Plains, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT236 DI 10.1158/1538-7445.AM2015-CT236 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100069 ER PT J AU Suswam, EA Putcha, BDK Tiwari, AK Jadhav, T Walker, KD Harkins, L Amer, S Eltoum, IE Bae, S Manne, U AF Suswam, Esther A. Putcha, Balananda-Dhurjati K. Tiwari, Amit K. Jadhav, Trafina Walker, Kiera D. Harkins, Lualhati Amer, Samir Eltoum, Isam-Eldin Bae, Sejong Manne, Upender TI Molecular and cellular localization profiles of tristetraprolin in colorectal cancer: Implications for tumor progression in diverse patient populations SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Suswam, Esther A.; Putcha, Balananda-Dhurjati K.; Jadhav, Trafina; Walker, Kiera D.; Eltoum, Isam-Eldin; Bae, Sejong; Manne, Upender] Univ Alabama Birmingham, Birmingham, AL USA. [Tiwari, Amit K.] Tuskegee Univ, Tuskegee, AL 36088 USA. [Harkins, Lualhati] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Amer, Samir] Natl Canc Inst, Cairo, Egypt. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4953 DI 10.1158/1538-7445.AM2015-4953 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105134 ER PT J AU Tamae, D Mostaghel, E Montgomery, B Nelson, PS Balk, SP Kantoff, PW Taplin, ME Penning, TM AF Tamae, Daniel Mostaghel, Elahe Montgomery, Bruce Nelson, Peter S. Balk, Steven P. Kantoff, Philip W. Taplin, Mary-Ellen Penning, Trevor M. TI Resistance to P450c17 inhibitors in castration-resistant prostate cancer may result from the DHEA-S depot that remains and can be used by AKR1C3 for intratumoral androgen biosynthesis SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Tamae, Daniel; Penning, Trevor M.] Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Ctr Canc Pharmacol, Philadelphia, PA 19104 USA. [Tamae, Daniel; Penning, Trevor M.] Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, CEET, Philadelphia, PA 19104 USA. [Mostaghel, Elahe; Montgomery, Bruce; Nelson, Peter S.] Univ Washington, Fred Hutchinson Canc Ctr, Seattle, WA 98195 USA. [Balk, Steven P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Kantoff, Philip W.; Taplin, Mary-Ellen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3450 DI 10.1158/1538-7445.AM2015-3450 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597101474 ER PT J AU Tan, WW Wilner, KD Lanzalone, S Polli, A Zierhut, ML Nickens, D O'Byrne, KJ Blackhall, FH Shaw, AT Salgia, R Jaime, JC Kim, DW AF Tan, Weiwei Wilner, Keith D. Lanzalone, Silvana Polli, Anna Zierhut, Matthew L. Nickens, Dana O'Byrne, Kenneth J. Blackhall, Fiona H. Shaw, Alice T. Salgia, Ravi Jaime, Jesus Correl Kim, Dong-Wan TI Evaluation of the effect of crizotinib (CRZ) on the QT interval in patients with ALK-positive non-small cell lung cancer (NSCLC) SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Tan, Weiwei; Wilner, Keith D.] Pfizer Inc, Oncol Business Unit, San Diego, CA USA. [Lanzalone, Silvana; Polli, Anna] Pfizer Inc, Oncol Business Unit, Milan, Italy. [Zierhut, Matthew L.; Nickens, Dana] Pfizer Inc, Global Clin Pharmacol, Pharmacometr, San Diego, CA USA. [O'Byrne, Kenneth J.] St James Hosp, Dept Med Oncol, Dublin 8, Ireland. [Blackhall, Fiona H.] Christie Hosp NHS Trust, Dept Med Oncol, Manchester M20 4BX, Lancs, England. [Shaw, Alice T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Salgia, Ravi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Jaime, Jesus Correl] Hosp Univ Virgen Rocio, Serv Oncol, Seville, Spain. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA CT117 DI 10.1158/1538-7445.AM2015-CT117 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100014 ER PT J AU Tangutoori, S Bladwin, P Ohman, A Korideck, H Cormack, R Dinulescu, D Makrigiorgos, M Sridhar, S AF Tangutoori, Shifalika Bladwin, Paige Ohman, Anders Korideck, Houari Cormack, Robert Dinulescu, Daniela Makrigiorgos, Mike Sridhar, Srinivas TI NanoPARPi inhibitors for ovarian and prostate cancer therapy SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Tangutoori, Shifalika; Bladwin, Paige; Sridhar, Srinivas] Northeastern Univ, Boston, MA 02115 USA. [Ohman, Anders; Dinulescu, Daniela] Brigham & Womens Hosp, Boston, MA 02115 USA. [Korideck, Houari; Cormack, Robert; Makrigiorgos, Mike] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3670 DI 10.1158/1538-7445.AM2015-3670 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597102209 ER PT J AU Tenente, IM Ignatius, M Chen, E Hayes, M Langenau, DM AF Tenente, Ines M. Ignatius, Myron Chen, Eleanor Hayes, Madeline Langenau, David M. TI Myogenic regulatory factors and their role in embryonal rhabdomyosarcoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Tenente, Ines M.; Ignatius, Myron; Chen, Eleanor; Hayes, Madeline; Langenau, David M.] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 5153 DI 10.1158/1538-7445.AM2015-5153 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105331 ER PT J AU Toniolo, PA Pilarski, PM Bach, C Griffin, JD Adamia, S AF Toniolo, Patricia A. Pilarski, Patrick M. Bach, Christian Griffin, James D. Adamia, Sophia TI MicroRNAs as potential therapeutic agents for AML: Targeting the AML1-ETO Oncogene by pre-miR-520 and-373 SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Toniolo, Patricia A.; Griffin, James D.; Adamia, Sophia] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pilarski, Patrick M.] Univ Alberta, Edmonton, AB, Canada. [Bach, Christian] Univ Hosp Erlangen, Erlangen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3972 DI 10.1158/1538-7445.AM2015-3972 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597103066 ER PT J AU Toniolo, PA Liu, S Walker, SR Barbuto, JAM Frank, DA AF Toniolo, Patricia A. Liu, Suhu Walker, Sarah R. Barbuto, Jose Alexandre M. Frank, David A. TI SOCS5 mediates defective function of monocyte-derived dendritic cells in patients with chronic lymphocytic leukemia SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Toniolo, Patricia A.; Liu, Suhu; Walker, Sarah R.; Frank, David A.] Dana Farber Canc Inst, Brookline, MA USA. [Barbuto, Jose Alexandre M.] Univ Sao Paulo, Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA LB-230 DI 10.1158/1538-7445.AM2015-LB-230 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597100325 ER PT J AU Tseng, E Clark, T Ashby, MH Shenykman, G AF Tseng, Elizabeth Clark, Tyson Ashby, Meredith H. Shenykman, Gloria TI Full-length isoform sequencing of the human MCF-7 cell line using PacBio long reads SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Tseng, Elizabeth; Clark, Tyson; Ashby, Meredith H.] Pacific Biosci, Menlo Pk, CA USA. [Shenykman, Gloria] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Shenykman, Gloria] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4898 DI 10.1158/1538-7445.AM2015-4898 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105082 ER PT J AU Van Allen, EM AF Van Allen, Eliezer M. TI Clinical whole exome interpretation for precision cancer medicine SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Van Allen, Eliezer M.] Dana Farber Canc Inst, Brookline, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA SY16-02 DI 10.1158/1538-7445.AM2015-SY16-02 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597101003 ER PT J AU VanderVeen, NT Raja, N Yi, E Curtin, J Chockley, P Assi, H Sayakus, J Mikkelsen, T Rabkin, S Lowenstein, PR Castro, MG AF VanderVeen, Nathan T. Raja, Nicholas Yi, Elizabeth Curtin, James Chockley, Peter Assi, Hikmat Sayakus, Jonathan Mikkelsen, Tom Rabkin, Samuel Lowenstein, Pedro R. Castro, Maria G. TI STAT3 inhibition using shRNA inhibits GBM proliferation, cell migration, anchorage-independent growth of mouse, rat, and human stem-like cells in vitro; and it induces long term survival and anti-GBM immunity in vivo SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [VanderVeen, Nathan T.; Raja, Nicholas; Yi, Elizabeth; Chockley, Peter; Assi, Hikmat; Sayakus, Jonathan; Lowenstein, Pedro R.; Castro, Maria G.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Curtin, James] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Rabkin, Samuel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 3195 DI 10.1158/1538-7445.AM2015-3195 PG 1 WC Oncology SC Oncology GA DF8HA UT WOS:000371597101229 ER PT J AU Wang, LZ Xu, YJ Wu, SL Fergus, M Wu, CL Zetter, B AF Wang, Liangzhe Xu, Yingjie Wu, Shulin Fergus, Mary Wu, Chin-Lee Zetter, Bruce TI Nuclear expression of antizyme inhibitor is associated with poor prostate cancer prognosis SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Wang, Liangzhe; Xu, Yingjie; Fergus, Mary; Zetter, Bruce] Boston Childrens Hosp, Boston, MA USA. [Wu, Shulin; Wu, Chin-Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4340 DI 10.1158/1538-7445.AM2015-4340 PG 3 WC Oncology SC Oncology GA DF8HA UT WOS:000371597103422 ER PT J AU Wei, W Birrer, MJ AF Wei, Wei Birrer, Michael J. TI TGF-beta signaling inhibition as a potential approach to target suboptimally debulked ovarian tumors SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Wei, Wei; Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI WEI, WEI/0000-0002-2315-3558 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 5401 DI 10.1158/1538-7445.AM2015-5401 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597106060 ER PT J AU Yuan, TL Bagni, R Yi, M Amzallag, A Afghani, S Beam, K Burgan, W Fer, N Garvey, L Smith, B Waters, A Stephens, R Benes, C McCormick, F AF Yuan, Tina L. Bagni, Rachel Yi, Ming Amzallag, Arnaud Afghani, Shervin Beam, Katie Burgan, William Fer, Nicole Garvey, Leslie Smith, Brian Waters, Andrew Stephens, Robert Benes, Cyril McCormick, Frank TI Next-generation screen for integrative subtyping and target discovery for KRAS-mutant cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Yuan, Tina L.; Afghani, Shervin; McCormick, Frank] UCSF Helen Diller Comprehens Canc Ctr, San Francisco, CA USA. [Bagni, Rachel; Yi, Ming; Beam, Katie; Burgan, William; Fer, Nicole; Garvey, Leslie; Smith, Brian; Waters, Andrew; Stephens, Robert] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res Technol Program, Frederick, MD USA. [Amzallag, Arnaud; Benes, Cyril] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA USA. [Amzallag, Arnaud; Benes, Cyril] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4690 DI 10.1158/1538-7445.AM2015-4690 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597104318 ER PT J AU Zheng, ZL Shetty, R Liebers, M Cambry, JL Bernardo, LA Borger, D Le, LP Lafrate, JA AF Zheng, Zongli Shetty, Ranjit Liebers, Matthew Cambry, Jessica L. Bernardo, Lindsay A. Borger, Darrell Le, Long P. Lafrate, John A. TI A one-tube assay for simultaneous detection of gene mutation, fusion, copy number alteration and expression SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Zheng, Zongli; Shetty, Ranjit; Liebers, Matthew; Cambry, Jessica L.; Bernardo, Lindsay A.; Borger, Darrell; Le, Long P.; Lafrate, John A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 4895 DI 10.1158/1538-7445.AM2015-4895 PG 2 WC Oncology SC Oncology GA DF8HA UT WOS:000371597105080 ER PT J AU Ahearn, TU Pettersson, A Ebot, EM Gerke, T De Morais, C Hicks, J Wilson, KM Rider, JR Fiorentino, M Finn, S Giovannucci, EL Loda, M Stampfer, MJ De Marzo, AM Mucci, LA Lotan, TL AF Ahearn, Thomas U. Pettersson, Andreas Ebot, Ericka M. Gerke, Travis De Morais, Carlos Hicks, Jessica Wilson, Kathryn M. Rider, Jennifer R. Fiorentino, Michelangelo Finn, Stephen Giovannucci, Edward L. Loda, Massimo Stampfer, Meir J. De Marzo, Angelo M. Mucci, Lorelei A. Lotan, Tamara L. TI A prospective investigation of PTEN loss and ERG expression in lethal prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Ahearn, Thomas U.; Pettersson, Andreas; Ebot, Ericka M.; Gerke, Travis; Wilson, Kathryn M.; Rider, Jennifer R.; Giovannucci, Edward L.; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [De Morais, Carlos; Hicks, Jessica; De Marzo, Angelo M.; Lotan, Tamara L.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Addarii Inst, Bologna, Italy. [Finn, Stephen] Trinity Coll Dublin, Dublin, Ireland. [Loda, Massimo] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 939 DI 10.1158/1538-7445.AM2015-939 PG 3 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501390 ER PT J AU Akbay, EA Koyama, S Li, Y Herter-Sprie, GS Thai, TC Aref, AR Soucheray, M Shimamura, T Barbie, DA Dranoff, G Hammerman, PS Wong, KK AF Akbay, Esra A. Koyama, Shohei Li, Yvonne Herter-Sprie, Grit S. Thai, Tran C. Aref, Amir R. Soucheray, Margaret Shimamura, Takeshi Barbie, David A. Dranoff, Glenn Hammerman, Peter S. Wong, Kwok-Kin TI Functional inactivation of LKB1 increases the production of pro-inflammatory cytokines and governs response to immune modulation SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Akbay, Esra A.; Koyama, Shohei; Li, Yvonne; Herter-Sprie, Grit S.; Thai, Tran C.; Aref, Amir R.; Barbie, David A.; Dranoff, Glenn; Hammerman, Peter S.; Wong, Kwok-Kin] DFCI, Boston, MA USA. [Soucheray, Margaret; Shimamura, Takeshi] Loyola Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1355 DI 10.1158/1538-7445.AM2015-1355 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502393 ER PT J AU Bergen, A Kim, E Brooks, A Shrestha, Y Tseng, YY Wu, XY Ilic, N Zou, LH Kamburov, A Yang, XP Zhu, C Keskula, P Seepo, S Hong, A Doench, J Subramanian, A Ligon, K Kantoff, P Janeway, K Garraway, L Root, D Golub, T Meyerson, M Hahn, W Getz, G Boehm, J AF Bergen, Alice Kim, Eejung Brooks, Angela Shrestha, Yashaswi Tseng, Yuen-Yi Wu, Xiaoyun Ilic, Nina Zou, Lihua Kamburov, Atanas Yang, Xiaoping Zhu, Cong Keskula, Paula Seepo, Sara Hong, Andrew Doench, John Subramanian, Aravind Ligon, Keith Kantoff, Philip Janeway, Katherine Garraway, Levi Root, David Golub, Todd Meyerson, Matthew Hahn, William Getz, Gad Boehm, Jesse TI Towards precision functional genomics via next-generation functional mapping of cancer variants SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Bergen, Alice; Kim, Eejung; Brooks, Angela; Shrestha, Yashaswi; Tseng, Yuen-Yi; Wu, Xiaoyun; Zou, Lihua; Yang, Xiaoping; Zhu, Cong; Keskula, Paula; Seepo, Sara; Doench, John; Subramanian, Aravind; Root, David; Golub, Todd; Boehm, Jesse] Broad Inst Harvard & MIT, Cambridge, MA USA. [Ilic, Nina; Hong, Andrew; Ligon, Keith; Kantoff, Philip; Janeway, Katherine; Garraway, Levi; Meyerson, Matthew; Hahn, William] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kamburov, Atanas; Getz, Gad] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 957 DI 10.1158/1538-7445.AM2015-957 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502005 ER PT J AU Bhang, HEC Ruddy, DA Radhakrishna, VK Zhao, R Kao, I Rakiec, D Shaw, P Balak, M Caushi, JX Ackley, E Keen, N Schlabach, MR Palmer, M Sellers, WR Michor, F Cooke, VG Korn, JM Stegmeier, F AF Bhang, Hyo-eun C. Ruddy, David A. Radhakrishna, Viveksagar Krishnamurthy Zhao, Rui Kao, Iris Rakiec, Daniel Shaw, Pamela Balak, Marissa Caushi, Justina X. Ackley, Elizabeth Keen, Nicholas Schlabach, Michael R. Palmer, Michael Sellers, William R. Michor, Franziska Cooke, Vesselina G. Korn, Joshua M. Stegmeier, Frank TI High complexity barcoding to study clonal dynamics in response to cancer therapy SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Bhang, Hyo-eun C.; Ruddy, David A.; Radhakrishna, Viveksagar Krishnamurthy; Kao, Iris; Rakiec, Daniel; Shaw, Pamela; Balak, Marissa; Caushi, Justina X.; Ackley, Elizabeth; Keen, Nicholas; Schlabach, Michael R.; Palmer, Michael; Sellers, William R.; Cooke, Vesselina G.; Korn, Joshua M.; Stegmeier, Frank] Novartis Inst BioMed Res, Cambridge, MA USA. [Zhao, Rui; Michor, Franziska] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2847 DI 10.1158/1538-7445.AM2015-2847 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505430 ER PT J AU Blackburn, JS Molodstov, A Lobbardi, R Moore, F Langeau, D AF Blackburn, Jessica S. Molodstov, Aleksey Lobbardi, Riadh Moore, Finola Langeau, David TI The tyrosine phosphatase PRL3 as a novel drug target in T-cell acute lymphoblastic leukemia SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Blackburn, Jessica S.; Molodstov, Aleksey; Lobbardi, Riadh; Moore, Finola; Langeau, David] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1725 DI 10.1158/1538-7445.AM2015-1725 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578503212 ER PT J AU Brown, KC Lau, JK Perry, HE Thornhill, BA Stevenson, CD Rollyson, WD Stover, CA Jones, DV Pulliam, JF Dasgupta, P AF Brown, Kathleen C. Lau, Jamie K. Perry, Haley E. Thornhill, Brent A. Stevenson, Cathryn D. Rollyson, William D. Stover, Cody A. Jones, Dennie V. Pulliam, Joseph F. Dasgupta, Piyali TI The acetylcholine signaling pathway: A novel molecular target for lung cancers SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Brown, Kathleen C.; Lau, Jamie K.; Perry, Haley E.; Thornhill, Brent A.; Stevenson, Cathryn D.; Rollyson, William D.; Stover, Cody A.; Dasgupta, Piyali] Marshall Univ, Joan C Edwards Sch Med, Huntington, WV USA. [Jones, Dennie V.] St Elizabeths Med Ctr, Dana Farber Canc Inst, Brighton, MA USA. [Pulliam, Joseph F.] Univ Kentucky, Markey Canc Ctr, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1032 DI 10.1158/1538-7445.AM2015-1032 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502078 ER PT J AU Cao, Y Nishihara, R Wu, KN Wang, ML Ogino, S Spiegelman, D Fuchs, CS Giovannucci, EL Chan, AT AF Cao, Yin Nishihara, Reiko Wu, Kana Wang, Molin Ogino, Shuji Spiegelman, Donna Fuchs, Charles S. Giovannucci, Edward L. Chan, Andrew T. TI Long-term use of aspirin and risk of cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Cao, Yin; Wu, Kana; Wang, Molin; Spiegelman, Donna; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Nishihara, Reiko; Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nishihara, Reiko; Ogino, Shuji; Fuchs, Charles S.; Giovannucci, Edward L.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 876 DI 10.1158/1538-7445.AM2015-876 PG 3 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501328 ER PT J AU Choueiri, TK Fishman, MN Escudier, B Stadler, WM Chasalow, S Ross-Macdonald, P Jure-Kunkel, M Sznol, M Simon, JS AF Choueiri, Toni K. Fishman, Mayer N. Escudier, Bernard Stadler, Walter M. Chasalow, Scott Ross-Macdonald, Petra Jure-Kunkel, Maria Sznol, Mario Simon, Jason S. TI Biomarker results from a clinical trial of nivolumab in patients (pts) with metastatic renal cell carcinoma (mRCC) (CA209-009): Gene expression, serum profiling for immune markers, and multiplex tissue immunohistochemistry (IHC) SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Fishman, Mayer N.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Escudier, Bernard] Inst Gustave Roussy, Villejuif, France. [Stadler, Walter M.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Chasalow, Scott; Ross-Macdonald, Petra; Jure-Kunkel, Maria; Simon, Jason S.] Bristol Myers Squibb Co, Princeton, NJ USA. [Sznol, Mario] Yale Univ, Sch Med, New Haven, CT USA. [Sznol, Mario] Yale Canc Ctr, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1306 DI 10.1158/1538-7445.AM2015-1306 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502344 ER PT J AU Devaraj, SGT Shah, B Fiskus, W Sun, BH Saha, S Pingali, SR Iyer, SP Sharma, S Bradner, JE Bhalla, KN AF Devaraj, Santhana G. T. Shah, Bhavin Fiskus, Warren Sun, Baohua Saha, Saikat Pingali, Sai Ravi Iyer, Swaminathan P. Sharma, Sunil Bradner, James E. Bhalla, Kapil N. TI Molecular mechanism of synergy between BET-protein bromodomain antagonist (BA) and pTEFb kinase inhibitor against human AML blast progenitor cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Devaraj, Santhana G. T.; Shah, Bhavin; Sun, Baohua; Saha, Saikat; Pingali, Sai Ravi; Iyer, Swaminathan P.; Bhalla, Kapil N.] Houston Methodist Res Inst, Houston, TX USA. [Fiskus, Warren] Baylor Coll Med, Houston, TX 77030 USA. [Sharma, Sunil] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2623 DI 10.1158/1538-7445.AM2015-2623 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505214 ER PT J AU Dias-Santos, D Ligorio, M Arora, K Thapar, V MacKenzie, OC Sil, S Desai, N Deshpande, V Rivera, MN Ferrone, CR Ting, DT AF Dias-Santos, Daniela Ligorio, Matteo Arora, Kshitij Thapar, Vishal MacKenzie, Olivia C. Sil, Srinjoy Desai, Niyati Deshpande, Vikram Rivera, Miguel N. Ferrone, Cristina R. Ting, David T. TI Molecular subtyping of pancreatic adenocarcinoma identifies SV2 positive subpopulation in classical PDAC SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Dias-Santos, Daniela] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Chron Dis Res Ctr,Nova Med Sch, Boston, MA USA. [Ligorio, Matteo; Arora, Kshitij; Ferrone, Cristina R.] Massachusetts Gen Hosp, Ctr Canc, Dept Surg, Boston, MA USA. [Arora, Kshitij; Deshpande, Vikram; Rivera, Miguel N.] Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA USA. [Thapar, Vishal; MacKenzie, Olivia C.; Sil, Srinjoy; Desai, Niyati] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Ting, David T.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 609 DI 10.1158/1538-7445.AM2015-609 PG 3 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501066 ER PT J AU Du, LL Zhang, TH Kaoud, T Gray, N Dalby, K Tsai, KY AF Du, Lili Zhang, Tinghu Kaoud, Tamer Gray, Nathanael Dalby, Kevin Tsai, Kenneth Y. TI Distinct roles of c-Jun N-terminal kinase (JNK) isoforms in skin cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Du, Lili; Tsai, Kenneth Y.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zhang, Tinghu; Gray, Nathanael] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kaoud, Tamer; Dalby, Kevin] Univ Texas Austin, Austin, TX 78712 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1941 DI 10.1158/1538-7445.AM2015-1941 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504051 ER PT J AU Emens, LA Braiteh, FS Cassier, P Delord, JP Eder, JP Fasso, M Xiao, YY Wang, Y Molinere, L Chen, DS Krop, I AF Emens, Leisha A. Braiteh, Fadi S. Cassier, Philippe Delord, Jean-Pierre Eder, Joseph Paul Fasso, Marcella Xiao, Yuanyuan Wang, Yan Molinere, Luciana Chen, Daniel S. Krop, Ian TI Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer (TNBC) SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Emens, Leisha A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Braiteh, Fadi S.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Cassier, Philippe] Ctr Leon Berard, F-69373 Lyon, France. [Delord, Jean-Pierre] Inst Claudius Regaud, Toulouse, France. [Eder, Joseph Paul] Yale Univ, Sch Med, New Haven, CT USA. [Fasso, Marcella; Xiao, Yuanyuan; Wang, Yan; Molinere, Luciana; Chen, Daniel S.] Genentech Inc, San Francisco, CA 94080 USA. [Krop, Ian] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 12 Z9 13 U1 9 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2859 DI 10.1158/1538-7445.AM2015-2859 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578506006 ER PT J AU Fofaria, NM Frederick, DT Sullivan, RJ Flaherty, KT Srivastava, SK AF Fofaria, Neel M. Frederick, Dennie T. Sullivan, Ryan J. Flaherty, Keith T. Srivastava, Sanjay K. TI Overexpression of Mcl-1 confers resistance to BRAFV600E inhibitors alone and in combination with MEK1/2 inhibitors in melanoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Fofaria, Neel M.; Srivastava, Sanjay K.] Texas Tech Univ, Hlth Sci Ctr, Amarillo, TX USA. [Frederick, Dennie T.; Sullivan, Ryan J.; Flaherty, Keith T.] Harvard Univ, Sch Med, Boston, MA USA. [Frederick, Dennie T.; Sullivan, Ryan J.; Flaherty, Keith T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2679 DI 10.1158/1538-7445.AM2015-2679 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505267 ER PT J AU Gao, S Gao, YF He, HS Brown, M Balk, S Cai, CM AF Gao, Shuai Gao, Yanfei He, Hansen Brown, Myles Balk, Steve Cai, Changmeng TI LSD1 functions as a global androgen receptor coactivator and is a therapeutic target in prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Gao, Shuai; Gao, Yanfei; Balk, Steve; Cai, Changmeng] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [He, Hansen] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Brown, Myles] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 966 DI 10.1158/1538-7445.AM2015-966 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502013 ER PT J AU Gao, Y Foster, R Hornicek, FJ Amiji, MM Duan, ZF AF Gao, Yan Foster, Rosemary Hornicek, Francis J. Amiji, Mansoor M. Duan, Zhenfeng TI Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Gao, Yan; Foster, Rosemary; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Amiji, Mansoor M.] Northeastern Univ, Sch Pharm, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 352 DI 10.1158/1538-7445.AM2015-352 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578500333 ER PT J AU Garcia, PL Miller, AL Kreitzburg, K Gamblin, TL Council, LN Christein, JD Arnoletti, P Heslin, M Reddy, S Richardson, JH Yang, ES Qi, J Bradner, JE Yoon, KJ AF Garcia, Patrick L. Miller, Aubrey L. Kreitzburg, Kelly Gamblin, Tracy L. Council, Leona N. Christein, John D. Arnoletti, Pablo Heslin, Marty Reddy, Sushanth Richardson, Joseph H. Yang, Eddy S. Qi, Jun Bradner, James E. Yoon, Karina J. TI Bromodomain inhibitor JQ1 inhibits cholangiocarcinoma tumor growth in patient-derived xenograft models SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Garcia, Patrick L.; Miller, Aubrey L.; Kreitzburg, Kelly; Gamblin, Tracy L.; Council, Leona N.; Christein, John D.; Heslin, Marty; Reddy, Sushanth; Richardson, Joseph H.; Yang, Eddy S.; Yoon, Karina J.] Univ Alabama Birmingham, Birmingham, AL USA. [Arnoletti, Pablo] Florida Hosp Orlando, Orlando, FL USA. [Arnoletti, Pablo] Univ Cent Florida, Orlando, FL 32816 USA. [Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1779 DI 10.1158/1538-7445.AM2015-1779 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578503264 ER PT J AU Gary, JM Xu, JF Simmons, J Zhang, SL Gamache, B Zhang, K Kovalchuk, A Michalowski, A Chen, JQ Herrmann, M Dubois, W Testa, J Mock, BA AF Gary, Joy M. Xu, Jinfei Simmons, John Zhang, Shuling Gamache, Benjamin Zhang, Ke Kovalchuk, Alexander Michalowski, Aleksandra Chen, Jin-Qiu Herrmann, Michelle Dubois, Wendy Testa, Joseph Mock, Beverly A. TI Murine model of dual mTORC kinase inhibition identifies CDK6 as a synergistic target in T-ALL SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Gary, Joy M.; Simmons, John; Zhang, Shuling; Gamache, Benjamin; Zhang, Ke; Michalowski, Aleksandra; Chen, Jin-Qiu; Herrmann, Michelle; Dubois, Wendy; Mock, Beverly A.] NCI, Bethesda, MD 20892 USA. [Xu, Jinfei] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Kovalchuk, Alexander] NIAID, Rockville, MD USA. [Testa, Joseph] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2309 DI 10.1158/1538-7445.AM2015-2309 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504411 ER PT J AU Ge, RB Wang, ZW Bechis, S Otsetov, A Hua, SY Wu, SL Wu, CL Tabatabaei, S Olumi, A AF Ge Rongbin Wang, Zongwei Bechis, Seth Otsetov, Alexander Hua, Shengyu Wu, Shulin Wu, Chin-Lee Tabatabaei, Shahin Olumi, Aria TI Variable expression of 5-alpha reductase 2 in the aging adult prostate is regulated by DNA methylation SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Ge Rongbin; Wang, Zongwei; Bechis, Seth; Otsetov, Alexander; Hua, Shengyu; Wu, Shulin; Wu, Chin-Lee; Tabatabaei, Shahin; Olumi, Aria] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1052 DI 10.1158/1538-7445.AM2015-1052 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502096 ER PT J AU Goicochea, NL Garnovskaya, M Blanton, M Chan, G Weisbart, R Lilly, M AF Goicochea, Nancy L. Garnovskaya, Maria Blanton, Mary Chan, Grace Weisbart, Richard Lilly, Michael TI Cell-penetrating bispecific antibodies for targeting androgen receptor signaling in advanced prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Goicochea, Nancy L.; Garnovskaya, Maria; Blanton, Mary; Lilly, Michael] Med Univ S Carolina, Charleston, SC 29425 USA. [Chan, Grace; Weisbart, Richard] Vet Affairs Greater Los Angeles Hlth Care Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 642 DI 10.1158/1538-7445.AM2015-642 PG 3 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501098 ER PT J AU Gokhale, PC Palakurthi, S Xu, M Calles, A Shah, SD O'Connell, A Messineo, M Kuang, YN Yanagita, M Ali, M Tran, CA Choi, J Ogino, A Butaney, M Redig, AJ Paweletz, C Kirschmeier, PT Janne, PA AF Gokhale, Prafulla C. Palakurthi, Sangeetha Xu, Man Calles, Antonio Shah, Shruti D. O'Connell, Allison Messineo, Melissa Kuang, Yanan Yanagita, Masahiko Ali, Mosab Tran, Cam Anh Choi, Jihyun Ogino, Atsuko Butaney, Mohit Redig, Amanda J. Paweletz, Cloud Kirschmeier, Paul T. Jaenne, Pasi A. TI Modeling patient-derived lung cancer in mice: Preclinical tool for drug development SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Gokhale, Prafulla C.; Palakurthi, Sangeetha; Xu, Man; Shah, Shruti D.; O'Connell, Allison; Messineo, Melissa; Kuang, Yanan; Yanagita, Masahiko; Ali, Mosab; Tran, Cam Anh; Paweletz, Cloud; Kirschmeier, Paul T.; Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. [Calles, Antonio; Choi, Jihyun; Ogino, Atsuko; Butaney, Mohit; Redig, Amanda J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1451 DI 10.1158/1538-7445.AM2015-1451 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502489 ER PT J AU Goldman, JW Karlovich, C Mann, E Rolfe, L Matheny, S Despain, D Angenendt, P Stamm, C Wakelee, HA Soria, JC Solomon, B Camidge, DR Dziadziuszko, R Horn, L Gadgeel, S Raponi, M Allen, AR Sequist, LV AF Goldman, Jonathan W. Karlovich, Chris Mann, Elaina Rolfe, Lindsey Matheny, Shannon Despain, Darrin Angenendt, Philipp Stamm, Claudia Wakelee, Heather A. Soria, Jean-Charles Solomon, Benjamin Camidge, D. R. Dziadziuszko, Rafal Horn, Leora Gadgeel, Shirish Raponi, Mitch Allen, Andrew R. Sequist, Lecia V. TI Pretreatment and serial plasma assessments of EGFR mutations in NSCLC patients treated with rociletinib (CO-1686) SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Goldman, Jonathan W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Karlovich, Chris; Mann, Elaina; Rolfe, Lindsey; Matheny, Shannon; Despain, Darrin; Raponi, Mitch; Allen, Andrew R.] Clovis Oncol, San Francisco, CA USA. [Angenendt, Philipp; Stamm, Claudia] Sysmex Inost GmbH, Hamburg, Germany. [Wakelee, Heather A.] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA. [Soria, Jean-Charles] South Paris Univ, Paris, France. [Solomon, Benjamin] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Camidge, D. R.] Univ Colorado, Aurora, CO USA. [Dziadziuszko, Rafal] Univ Gdansk, PL-80952 Gdansk, Poland. [Horn, Leora] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Gadgeel, Shirish] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 927 DI 10.1158/1538-7445.AM2015-927 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501378 ER PT J AU Groner, AC de Tribolet-Hardy, J Theurillat, JP Wild, PJ Brown, M AF Groner, Anna C. de Tribolet-Hardy, Jonas Theurillat, Jean-Philippe Wild, Peter J. Brown, Myles TI TRIM24 acts as a transcriptional co-activator of the androgen receptor during prostate cancer progression SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Groner, Anna C.; de Tribolet-Hardy, Jonas; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Theurillat, Jean-Philippe] Oncol Res Inst, Bellinzona, Switzerland. [Wild, Peter J.] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1865 DI 10.1158/1538-7445.AM2015-1865 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578503349 ER PT J AU Henssen, A Eisenberg, A Jiang, E Henaff, E Koche, R Burns, M Carson, JR Nanjangud, G Sti, E Gandara, J Cifani, P Dhabaria, A Huang, XD de Stanchina, E Mullen, E Steen, H Perlman, E Dome, J Antonescul, C Feschottel, C Mason, CE Kentsis, A AF Henssen, Anton Eisenberg, Amy Jiang, Eileen Henaff, Elizabeth Koche, Richard Burns, Melissa Carson, Julianne R. Nanjangud, Gouri Sti, Eric Gandara, Jorge Cifani, Paolo Dhabaria, Avantika Huang, Xiaodong de Stanchina, Elisa Mullen, Elizabeth Steen, Hanno Perlman, Elizabeth Dome, Jeffrey Antonescul, Cristina Feschottel, Cedric Mason, Christopher E. Kentsis, Alex TI Human tumorigenesis induced by endogenous DNA transposase SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Henssen, Anton; Eisenberg, Amy; Jiang, Eileen; Carson, Julianne R.; Cifani, Paolo; Dhabaria, Avantika; Kentsis, Alex] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Mol Pharmacol & Chem Program, New York, NY 10021 USA. [Henaff, Elizabeth; Gandara, Jorge; Mason, Christopher E.] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY USA. [Koche, Richard] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Burns, Melissa; Mullen, Elizabeth] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Nanjangud, Gouri; Sti, Eric] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Huang, Xiaodong; de Stanchina, Elisa] Mem Sloan Kettering Canc Ctr, Antitumor Assessment Core Facil, New York, NY 10021 USA. [Steen, Hanno] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Perlman, Elizabeth] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Dome, Jeffrey] Childrens Natl Med Ctr, Div Oncol, Washington, DC 20010 USA. [Antonescul, Cristina] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Feschottel, Cedric] Univ Utah, Dept Human Genet, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1103 DI 10.1158/1538-7445.AM2015-1103 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502145 ER PT J AU Hernandez, SF DiGloria, C Groeneweg, J Borger, D Foster, R Rueda, B Growdon, W AF Hernandez, Silvia F. DiGloria, Celeste Groeneweg, Jolijn Borger, Darrell Foster, Rosemary Rueda, Bo Growdon, Whitfield TI Phosphorylated HER3 levels associated with trastuzumab resistance in HER2 gene amplified uterine serous carcinoma xenograft tumors SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Hernandez, Silvia F.; DiGloria, Celeste; Groeneweg, Jolijn; Borger, Darrell; Foster, Rosemary; Rueda, Bo; Growdon, Whitfield] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 658 DI 10.1158/1538-7445.AM2015-658 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501114 ER PT J AU Hettmer, S Schinzel, AC Tchessalova, D Richards, NGJ Hahn, WC Wagers, AJ AF Hettmer, Simone Schinzel, Anna C. Tchessalova, Dada Richards, Nigel G. J. Hahn, William C. Wagers, Amy J. TI Functional genomic screening reveals asparagine dependence as a metabolic vulnerability in sarcoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Hettmer, Simone] Univ Childrens Hosp Freiburg, Freiburg, Germany. [Schinzel, Anna C.; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tchessalova, Dada] Joslin Diabet Ctr, Boston, MA 02215 USA. [Richards, Nigel G. J.] Indiana Univ, Indianapolis, IN 46204 USA. [Wagers, Amy J.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1187 DI 10.1158/1538-7445.AM2015-1187 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502228 ER PT J AU Hodi, FS Postow, MA Chesney, J Pavlick, AC Robert, C Grossmann, K McDermott, D Linette, G Meyer, N Giguere, J Agarwala, SS Shaheen, M Emstoff, MS Minor, DR Salama, A Taylor, MH Rollin, L Horak, C Gagnier, P Wolchok, JD AF Hodi, F. Stephen Postow, Michael A. Chesney, Jason Pavlick, Anna C. Robert, Caroline Grossmann, Kenneth McDermott, David Linette, Gerald Meyer, Nicolas Giguere, Jeffrey Agarwala, Sanjiv S. Shaheen, Montaser Emstoff, Marc S. Minor, David R. Salama, April Taylor, Matthew H. Rollin, Linda Horak, Christine Gagnier, Paul Wolchok, Jedd D. TI Improved clinical response in patients with advanced melanoma treated with nivolumab combined with ipilimumab compared to ipilimumab alone SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Postow, Michael A.; Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Chesney, Jason] Univ Louisville, Louisville, KY 40292 USA. [Pavlick, Anna C.] NYU, New York, NY USA. [Robert, Caroline] Gustave, Roussy, France. [Robert, Caroline] INSERM, U981, Villejuif Paris Sud, France. [Grossmann, Kenneth] Huntsman Canc Inst, Salt Lake City, UT USA. [McDermott, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Linette, Gerald] Washington Univ, St Louis, MO USA. [Meyer, Nicolas] Inst Univ Canc, Toulouse, France. [Giguere, Jeffrey] Greenville Hosp Ctr, Greenville, SC USA. [Agarwala, Sanjiv S.] St Lukes Canc Ctr, Bethlehem, PA USA. [Agarwala, Sanjiv S.] Temple Univ, Bethlehem, PA USA. [Shaheen, Montaser] Univ New Mexico, Albuquerque, NM 87131 USA. [Emstoff, Marc S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Minor, David R.] Calif Pacific Ctr Melanoma Res, San Francisco, CA USA. [Salama, April] Duke Univ, Durham, NC USA. [Taylor, Matthew H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Rollin, Linda; Gagnier, Paul] Bristol Myers Squibb, Wallingford, CT USA. [Horak, Christine] Bristol Myers Squibb, Lawrenceville, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2860 DI 10.1158/1538-7445.AM2015-2860 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578506007 ER PT J AU Hogdal, L Chyla, B McKeegan, E Leverson, J Potluri, J Falotico, N Ricker, J Humerickhouse, R Mabry, M Foight, G Keating, A Galinsky, I Stone, R DeAngelo, D Konopleva, M Letai, A AF Hogdal, Leah Chyla, Brenda McKeegan, Evelyn Leverson, Joel Potluri, Jalaja Falotico, Nancy Ricker, Justin Humerickhouse, Rod Mabry, Mack Foight, Glenna Keating, Amy Galinsky, Ilene Stone, Richard DeAngelo, Daniel Konopleva, Marina Letai, Anthony TI BH3 profiling predicts clinical response in a phase II clinical trial of ABT-199 (GDC-0199) in acute myeloid leukemia SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Hogdal, Leah; Galinsky, Ilene; Stone, Richard; DeAngelo, Daniel; Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chyla, Brenda; McKeegan, Evelyn; Leverson, Joel; Potluri, Jalaja; Falotico, Nancy; Ricker, Justin; Humerickhouse, Rod; Mabry, Mack] Abbvie Inc, N Chicago, IL USA. [Foight, Glenna; Keating, Amy] MIT, Cambridge, MA 02139 USA. [Konopleva, Marina] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2834 DI 10.1158/1538-7445.AM2015-2834 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505417 ER PT J AU Jakubikova, J Cholujova, D Hideshima, T Laubach, J Munshi, NC Treon, SP Richardson, PG Kastritis, E Dorfman, DM Anderson, KC AF Jakubikova, Jana Cholujova, Danka Hideshima, Teru Laubach, Jacob Munshi, Nikhil C. Treon, Steven P. Richardson, Paul G. Kastritis, Efstathios Dorfman, David M. Anderson, Kenneth C. TI Phenotypic and molecular characterization of inter- and intraclonal heterogeneity in multiple myeloma and Waldenstrom macroglobulinemia SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Jakubikova, Jana; Hideshima, Teru; Laubach, Jacob; Munshi, Nikhil C.; Treon, Steven P.; Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jakubikova, Jana; Hideshima, Teru; Laubach, Jacob; Munshi, Nikhil C.; Treon, Steven P.; Richardson, Paul G.; Dorfman, David M.; Anderson, Kenneth C.] HMS, Boston, MA USA. [Cholujova, Danka] Slovak Acad Sci, Canc Res Inst, Bratislava, Slovakia. [Kastritis, Efstathios] Univ Athens, Sch Med, Athens 11528, Greece. [Dorfman, David M.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2004 DI 10.1158/1538-7445.AM2015-2004 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504111 ER PT J AU Kulkarni, MM Gurumurthy, S Schmidt-Kittler, O Berglund, J Hulton, CH Wilson, DJ Jakubosky, D Michaud, D Jones, RE Sjoblom, NM McSweeney, R Zhou, HW Venkatakrishnan, A Jensen, KJ Zhang, JX Mankoo, PK Pollard, J Winter, C Janne, PA Wong, KK Richon, VM English, JM Bittinger, MA AF Kulkarni, Meghana M. Gurumurthy, Sushma Schmidt-Kittler, Oleg Berglund, Jason Hulton, Christopher H. Wilson, David J. Jakubosky, David Michaud, Daniel Jones, Robert E. Sjoblom, Nicole M. McSweeney, Russell Zhou, Hongwei Venkatakrishnan, Annapurna Jensen, Karin J. Zhang, Jingxin Mankoo, Parminder K. Pollard, Jack Winter, Christopher Jaenne, Pasi A. Wong, Kwok-Kin Richon, Victoria M. English, Jessie M. Bittinger, Mark A. TI Functional genomics reveals genetic dependencies in gastric cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Kulkarni, Meghana M.; Gurumurthy, Sushma; Berglund, Jason; Hulton, Christopher H.; Wilson, David J.; Jakubosky, David; Michaud, Daniel; Jones, Robert E.; Sjoblom, Nicole M.; McSweeney, Russell; Zhou, Hongwei; Venkatakrishnan, Annapurna; Jaenne, Pasi A.; Wong, Kwok-Kin; English, Jessie M.; Bittinger, Mark A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. [Schmidt-Kittler, Oleg; Jensen, Karin J.; Zhang, Jingxin; Mankoo, Parminder K.; Pollard, Jack; Winter, Christopher; Richon, Victoria M.] Sanofi, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1110 DI 10.1158/1538-7445.AM2015-1110 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502152 ER PT J AU Kumar, R Belz, J Korideck, H Cormack, R Makrigiorgos, M Sridhar, S AF Kumar, Rajiv Belz, Jodi Korideck, Houari Cormack, Robert Makrigiorgos, Mike Sridhar, Srinivas TI Local chemotherapy and chemoradiation therapy using INCeRT brachytherapy implants in cancer models SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Kumar, Rajiv; Belz, Jodi; Sridhar, Srinivas] Northeastern Univ, Boston, MA 02115 USA. [Kumar, Rajiv; Belz, Jodi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Korideck, Houari; Cormack, Robert; Makrigiorgos, Mike] Dana Farber Canc Ctr, Boston, MA USA. [Sridhar, Srinivas] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1806 DI 10.1158/1538-7445.AM2015-1806 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578503291 ER PT J AU Kwong, LN Boland, G Frederick, D Helms, T Akid, A Miller, J Jiang, S Cooper, Z Song, XZ Seth, S Kamara, J Protopopov, A Mills, G Flaherty, K Wargo, J Chin, LD AF Kwong, Lawrence N. Boland, Genevieve Frederick, Dennie Helms, Timothy Akid, Ahmad Miller, John Jiang, Shan Cooper, Zachary Song, Xingzhi Seth, Sahil Kamara, Jennifer Protopopov, Alexei Mills, Gordon Flaherty, Keith Wargo, Jennifer Chin, Lynda TI A co-clinical assessment of patterns of BRAF inhibitor resistance SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Kwong, Lawrence N.; Boland, Genevieve; Helms, Timothy; Akid, Ahmad; Miller, John; Jiang, Shan; Cooper, Zachary; Song, Xingzhi; Seth, Sahil; Kamara, Jennifer; Protopopov, Alexei; Mills, Gordon; Wargo, Jennifer; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Frederick, Dennie; Flaherty, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2841 DI 10.1158/1538-7445.AM2015-2841 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505424 ER PT J AU LaQuaglia, MJ Grijalva, J Mueller, K Perez-Atayde, A Kim, HB Sadri-Vakili, G Vakili, K AF LaQuaglia, Michael J. Grijalva, James Mueller, Kaly Perez-Atayde, Antonio Kim, Heung Bae Sadri-Vakili, Ghazaleh Vakili, Khashayar TI YAP protein expression and subcellular localization in pediatric liver tumors SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [LaQuaglia, Michael J.; Grijalva, James; Perez-Atayde, Antonio; Kim, Heung Bae; Vakili, Khashayar] Boston Childrens Hosp, Boston, MA USA. [Mueller, Kaly; Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2107 DI 10.1158/1538-7445.AM2015-2107 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504212 ER PT J AU Lawrenson, K Kar, S Kuckenbaeker, K Edwards, S Li, QY Tyrer, J Beesley, J Michailidou, K Ramus, S Dunning, A Couch, F Monteiro, A Simard, J Freedman, M Easton, D Chenevix-Trench, G Pharoah, P Antoniou, A Gayther, S AF Lawrenson, Kate Kar, Siddhartha Kuckenbaeker, Karoline Edwards, Stacey Li, Qiyuan Tyrer, Jonathan Beesley, Jonathan Michailidou, Kyriaki Ramus, Susan Dunning, Alison Couch, Fergus Monteiro, Alvaro Simard, Jacques Freedman, Matthew Easton, Douglas Chenevix-Trench, Georgia Pharoah, Paul Antoniou, Antonis Gayther, Simon CA OCAC BCAC CIMBA TI Common functional mechanisms underlying pleiotropy at the 19p13.1 breast and ovarian cancer cusceptibility locus SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Lawrenson, Kate; Ramus, Susan; Gayther, Simon] USC, Los Angeles, CA USA. [Kar, Siddhartha; Kuckenbaeker, Karoline; Tyrer, Jonathan; Michailidou, Kyriaki; Easton, Douglas; Pharoah, Paul; Antoniou, Antonis] Univ Cambridge, Cambridge, England. [Edwards, Stacey; Beesley, Jonathan; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Li, Qiyuan; Freedman, Matthew] Dana Faber Canc Ctr, Boston, MA USA. [Couch, Fergus] Mayo Clin, Rochester, MN USA. [Monteiro, Alvaro] Moffit Canc Ctr, Tampa, FL USA. [Simard, Jacques] CHUL, Quebec City, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2783 DI 10.1158/1538-7445.AM2015-2783 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505369 ER PT J AU le Calve, B Deschenes-Ximard, X Kottakis, F Bourdeau, V Lessard, F Moineau-Vallee, K Saint-Germain, E Fitamant, J Perera, RM Bardeesy, N Ferbeyre, G AF le Calve, Benjamin Deschenes-Ximard, Xavier Kottakis, Filippos Bourdeau, Veronique Lessard, Frederic Moineau-Vallee, Karine Saint-Germain, Emmanuelle Fitamant, Julien Perera, Rushika Miriam Bardeesy, Nabeel Ferbeyre, Gerardo TI ERK/MAPK pathway inhibits tumorigenesis and cellular reprogramming of pancreatic cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [le Calve, Benjamin; Deschenes-Ximard, Xavier; Bourdeau, Veronique; Lessard, Frederic; Moineau-Vallee, Karine; Saint-Germain, Emmanuelle; Ferbeyre, Gerardo] Univ Montreal, Montreal, PQ, Canada. [Kottakis, Filippos; Fitamant, Julien; Perera, Rushika Miriam; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2154 DI 10.1158/1538-7445.AM2015-2154 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504259 ER PT J AU Li, H Talukdar, J Sandhya, S Bhuyan, S Gayan, S Sarma, A Mokhtari, RB Felsher, DW Yeger, H Das, B AF Li, Hong Talukdar, Joyeeta Sandhya, Sora Bhuyan, Seema Gayan, Sukanya Sarma, Anupam Mokhtari, Reza Bayat Felsher, Dean W. Yeger, Herman Das, Bikul TI MYC and HIF-2alpha cooperates in oral squamous carcinoma cell self-renewal during hypoxia SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Li, Hong; Gayan, Sukanya; Das, Bikul] Forsyth Inst, Cambridge, MA USA. [Talukdar, Joyeeta; Sandhya, Sora; Bhuyan, Seema; Sarma, Anupam] KaviKrishna Lab, Guwahati Biotech Pk, Gauhati, India. [Mokhtari, Reza Bayat; Yeger, Herman] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Felsher, Dean W.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1529 DI 10.1158/1538-7445.AM2015-1529 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578503024 ER PT J AU Li, J Kozono, D Nitta, M Sampetrean, O Gonda, D Kushwaha, DS Merzon, D Ramakrishnan, V Zhu, S Zhu, KY Matsui, H Harismendy, O Hua, W Mao, Y Kwon, CH Saya, H Carter, BS Pizzo, DP VandenBerg, SR Chen, CC AF Li, Jie Kozono, David Nitta, Masayuki Sampetrean, Oltea Gonda, David Kushwaha, Deepa S. Merzon, Dmitry Ramakrishnan, Valya Zhu, Shan Zhu, Kaya Matsui, Hiroko Harismendy, Olivier Hua, Wei Mao, Ying Kwon, Chang-Hyuk Saya, Hideyuki Carter, Bob S. Pizzo, Donald P. VandenBerg, Scott R. Chen, Clark C. TI Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Li, Jie; Gonda, David; Ramakrishnan, Valya; Carter, Bob S.; Chen, Clark C.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Kozono, David; Nitta, Masayuki; Kushwaha, Deepa S.; Merzon, Dmitry; Zhu, Shan; Zhu, Kaya] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Sampetrean, Oltea; Saya, Hideyuki] Keio Univ, Sch Med, Div Gene Regulat, Tokyo, Japan. [Matsui, Hiroko; Harismendy, Olivier] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. [Matsui, Hiroko; Harismendy, Olivier] Univ Calif San Diego, Rady Childrens Hosp, La Jolla, CA 92093 USA. [Hua, Wei; Mao, Ying] Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai 200433, Peoples R China. [Kwon, Chang-Hyuk] Ohio State Univ, Med Ctr, Dept Med Oncol, Columbus, OH 43210 USA. [Pizzo, Donald P.; VandenBerg, Scott R.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 979 DI 10.1158/1538-7445.AM2015-979 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502025 ER PT J AU Lin, L Abo, R Dolcen, D Paquette, R Laing, A de Waal, L Thorner, A Ducar, M Ziaugra, L Wollison, B Breneiser, M Hahn, W Meyerson, M Van Hummelen, P MacConaill, L AF Lin, Ling Abo, Ryan Dolcen, Deniz Paquette, Rachel Laing, Angelica de Waal, Luc Thorner, Aaron Ducar, Matthew Ziaugra, Liuda Wollison, Bruce Breneiser, Marc Hahn, William Meyerson, Matthew Van Hummelen, Paul MacConaill, Laura TI Targeted RNA sequencing improves transcript analysis in cancer samples SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Lin, Ling; Abo, Ryan; Dolcen, Deniz; Paquette, Rachel; Laing, Angelica; de Waal, Luc; Thorner, Aaron; Ducar, Matthew; Ziaugra, Liuda; Wollison, Bruce; Breneiser, Marc; Hahn, William; Meyerson, Matthew; Van Hummelen, Paul; MacConaill, Laura] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1115 DI 10.1158/1538-7445.AM2015-1115 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502157 ER PT J AU Marino-Enriquez, A Eilers, G Czaplinski, J Mayeda, M Tao, D Zhu, MJ Hornick, JL Sicinska, E Wagner, AJ Fletcher, JA AF Marino-Enriquez, Adrian Eilers, Grant Czaplinski, Jeffrey Mayeda, Mark Tao, Derrick Zhu, Meijun Hornick, Jason L. Sicinska, Ewa Wagner, Andrew J. Fletcher, Jonathan A. TI Genomic analyses and novel models validate CDK4 as a therapeutic target in imatinib-resistant dermatofibrosarcoma protuberans SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Marino-Enriquez, Adrian; Eilers, Grant; Mayeda, Mark; Tao, Derrick; Zhu, Meijun; Hornick, Jason L.; Fletcher, Jonathan A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Marino-Enriquez, Adrian; Eilers, Grant; Czaplinski, Jeffrey; Mayeda, Mark; Tao, Derrick; Zhu, Meijun; Hornick, Jason L.; Sicinska, Ewa; Wagner, Andrew J.; Fletcher, Jonathan A.] Harvard Univ, Sch Med, Boston, MA USA. [Czaplinski, Jeffrey; Sicinska, Ewa; Wagner, Andrew J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 607 DI 10.1158/1538-7445.AM2015-607 PG 3 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501064 ER PT J AU McCarthy, AM Keller, B Synnestvedt, M Conant, E Armstrong, K Kontos, D AF McCarthy, Anne Marie Keller, Brad Synnestvedt, Marie Conant, Emily Armstrong, Katrina Kontos, Despina TI Racial differences in quantitative measures of area and volumetric breast density SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [McCarthy, Anne Marie; Armstrong, Katrina] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Keller, Brad; Synnestvedt, Marie; Conant, Emily; Kontos, Despina] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2770 DI 10.1158/1538-7445.AM2015-2770 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505356 ER PT J AU Moore, NF Chipumuro, E Hatheway, CM Zhang, TH Gray, NS George, RE AF Moore, Nathan F. Chipumuro, Edmond Hatheway, Clark M. Zhang, Tinghu Gray, Nathanael S. George, Rani E. TI A high-throughput chemical screen identifies synergistic activity between crizotinib and transcriptional CDK inhibitors in ALK-mutated neuroblastoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Moore, Nathan F.; Chipumuro, Edmond; Hatheway, Clark M.; Zhang, Tinghu; Gray, Nathanael S.; George, Rani E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2195 DI 10.1158/1538-7445.AM2015-2195 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504300 ER PT J AU Nabavi, S Schmolze, D Maitituoheti, M Beck, AH AF Nabavi, Sheida Schmolze, Daniel Maitituoheti, Mayinuer Beck, Andrew H. TI Earth mover's distance for the identification of genes associated with drug resistance in cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Nabavi, Sheida] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Schmolze, Daniel; Beck, Andrew H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Schmolze, Daniel; Maitituoheti, Mayinuer; Beck, Andrew H.] Harvard Univ, Sch Med, Boston, MA USA. [Maitituoheti, Mayinuer] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2172 DI 10.1158/1538-7445.AM2015-2172 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504277 ER PT J AU Nabet, B Broin, PO Reyes, J Shieh, K Lin, CY Will, CM Popovic, R Ezponda, T Bradner, JE Golden, AA Licht, JD AF Nabet, Behnam Broin, Pilib O. Reyes, Jaime Shieh, Kevin Lin, Charles Y. Will, Christine M. Popovic, Relja Ezponda, Teresa Bradner, James E. Golden, Aaron A. Licht, Jonathan D. TI Deregulation of the Ras-Erk signaling axis modulates the enhancer landscape SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Nabet, Behnam; Will, Christine M.; Popovic, Relja; Ezponda, Teresa; Licht, Jonathan D.] Northwestern Univ, Chicago, IL 60611 USA. [Broin, Pilib O.; Shieh, Kevin; Golden, Aaron A.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Reyes, Jaime; Lin, Charles Y.; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2209 DI 10.1158/1538-7445.AM2015-2209 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504314 ER PT J AU Nakayama, R Zhang, YX Anatone, A Sicinska, E Demetri, G Wagner, A AF Nakayama, Robert Zhang, Yi-Xiang Anatone, Alex Sicinska, Ewa Demetri, George Wagner, Andrew TI Preclinical activity of selinexor, an inhibitor of XPO1/CRM1, in sarcoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Nakayama, Robert; Zhang, Yi-Xiang; Anatone, Alex; Sicinska, Ewa; Demetri, George; Wagner, Andrew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1759 DI 10.1158/1538-7445.AM2015-1759 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578503244 ER PT J AU Nata, AN Niederst, MJ Archibald, HL Mulvey, H Ham, J Gomez-Caraballo, M Kalsy, A Faber, AC Engelman, J AF Nata, Aaron N. Niederst, Matthew J. Archibald, Hannah L. Mulvey, Hillary Ham, Jungoh Gomez-Caraballo, Maria Kalsy, Anuj Faber, Anthony C. Engelman, Jeffrey TI Co-acquisition of T790M and EMT in resistant EGFR mutant non-small cell lung cancer can be overcome by combined irreversible EGFR and BCL-XL inhibition SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Nata, Aaron N.; Niederst, Matthew J.; Archibald, Hannah L.; Mulvey, Hillary; Gomez-Caraballo, Maria; Kalsy, Anuj; Engelman, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ham, Jungoh; Faber, Anthony C.] Virginia Commonwealth Univ, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2845 DI 10.1158/1538-7445.AM2015-2845 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505428 ER PT J AU Neupane, M Clark, AP Birkbak, NJ Eklund, A Schumacher, SE Beroukhim, R Szallasi, Z Vidal, M Hill, DE Silver, DP AF Neupane, Manish Clark, Allison P. Birkbak, Nicolai J. Eklund, Aron Schumacher, Steven E. Beroukhim, Rameen Szallasi, Zoltan Vidal, Marc Hill, David E. Silver, Daniel P. TI MECP2 is a frequently amplified oncogene with an unusual epigenetic mechanism of action SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Neupane, Manish; Clark, Allison P.; Schumacher, Steven E.; Beroukhim, Rameen; Szallasi, Zoltan; Vidal, Marc; Hill, David E.; Silver, Daniel P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Birkbak, Nicolai J.; Eklund, Aron] Tech Univ Denmark, DK-2800 Lyngby, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2027 DI 10.1158/1538-7445.AM2015-2027 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504133 ER PT J AU Okazaki, A Gameiro, P Stephanopoulos, G Iliopoulos, O AF Okazaki, Arimichi Gameiro, Paulo Stephanopoulos, Gregory Iliopoulos, Othon TI Glutaminase inhibitors suppress pyrimidine synthesis and promote DNA replication stress in VHL-deficient human renal cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Okazaki, Arimichi; Gameiro, Paulo; Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Stephanopoulos, Gregory] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1123 DI 10.1158/1538-7445.AM2015-1123 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502165 ER PT J AU Palakurthi, SS Liu, JF Zeng, Q Zhou, S Huang, W Ivanova, E Paweletz, C Murgo, JR Evangelista, J Buttimer, M Curtis, J Piao, HY Gokhale, P Pritchard, C English, JM Kirschmeier, P Wong, KK Matulonis, UA Drapkin, R AF Palakurthi, Sangeetha S. Liu, Joyce F. Zeng, Qing Zhou, Shan Huang, Wei Ivanova, Elena Paweletz, Cloud Murgo, John R. Evangelista, Justin Buttimer, Melissa Curtis, Jennifer Piao, Huiying Gokhale, Prafulla Pritchard, Colin English, Jessie M. Kirschmeier, Paul Wong, Kwok-Kin Matulonis, Ursula A. Drapkin, Ronny TI Establishment, characterization, and clinical correlation of a platform of ovarian patient-derived xenograft (PDX) models SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Palakurthi, Sangeetha S.; Zeng, Qing; Zhou, Shan; Huang, Wei; Ivanova, Elena; Paweletz, Cloud; Murgo, John R.; Evangelista, Justin; Buttimer, Melissa; Gokhale, Prafulla; English, Jessie M.; Kirschmeier, Paul; Wong, Kwok-Kin] DFCI, Belfer Inst Appl Canc Sci, Boston, MA USA. [Liu, Joyce F.; Piao, Huiying; Matulonis, Ursula A.; Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Curtis, Jennifer] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Pritchard, Colin] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1471 DI 10.1158/1538-7445.AM2015-1471 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502509 ER PT J AU Paweletz, CP Raymond, CK Sacher, AG Kuang, Y O'Connell, A Lim, L Li, M Armour, C English, JM Kirschmeier, PT Janne, PA Oxnard, G AF Paweletz, Cloud P. Raymond, Chris K. Sacher, Adrian G. Kuang, Yanan O'Connell, Allison Lim, Lee Li, Mark Armour, Chris English, Jessie M. Kirschmeier, Paul T. Jaenne, Pasi A. Oxnard, Geoffrey TI Bias-corrected next generation sequencing of cell free DNA for detection of actionable mutations and rearrangements in advanced non-small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Paweletz, Cloud P.; Sacher, Adrian G.; Kuang, Yanan; O'Connell, Allison; English, Jessie M.; Kirschmeier, Paul T.; Jaenne, Pasi A.; Oxnard, Geoffrey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Raymond, Chris K.; Lim, Lee; Li, Mark; Armour, Chris] Clearfork Biosci, Bellevue, WA 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 AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 928 DI 10.1158/1538-7445.AM2015-928 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501379 ER PT J AU Ponichtera, HE Guerriero, JL Sotayo, AO Letai, A AF Ponichtera, Holly E. Guerriero, Jennifer L. Sotayo, Alaba O. Letai, Anthony TI Novel compound elicits antitumor macrophages associated with tumor regression in breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Ponichtera, Holly E.; Guerriero, Jennifer L.; Sotayo, Alaba O.; Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 460 DI 10.1158/1538-7445.AM2015-460 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578500439 ER PT J AU Rodriguez, CI Setaluri, V AF Rodriguez, Carlos I. Setaluri, Vijayasaradhi TI Cyclic AMP signaling in melanoma: Paradoxical downregulation of pCREB upon activation of adenylate cyclase confers resistance to MAPK inhibition SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Rodriguez, Carlos I.] Univ Wisconsin Madison, Dept Dermatol, Grad Program Mol & Environm Toxicol, Madison, WI USA. [Setaluri, Vijayasaradhi] Univ Wisconsin Madison, Dept Dermatol, William S Middleton Mem Vet Hosp, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2680 DI 10.1158/1538-7445.AM2015-2680 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505268 ER PT J AU Rueda, B Digloria, C Hall, T Foster, R Borger, D Growdon, W AF Rueda, Bo Digloria, Celeste Hall, Tracilyn Foster, Rosemary Borger, Darrell Growdon, Whitfield TI PI3K inhibition induces homologous repair defects in endometrioid endometrial cancer patient derived xenografts leading to synergistic anti-tumor activity with PARP inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Rueda, Bo; Digloria, Celeste; Hall, Tracilyn; Foster, Rosemary; Borger, Darrell; Growdon, Whitfield] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2666 DI 10.1158/1538-7445.AM2015-2666 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505254 ER PT J AU Sarosiek, KA Karst, A Winter, P Sorrentino, A Bandyopadhyay, S Goga, A Wood, KC Drapkin, R Letai, A AF Sarosiek, Kristopher A. Karst, Alison Winter, Peter Sorrentino, Antonio Bandyopadhyay, Sourav Goga, Andrei Wood, Kris C. Drapkin, Ronny Letai, Anthony TI Broad therapy resistance is induced by suppression of apoptotic priming by lineage programs and oncogenic activation SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Sarosiek, Kristopher A.; Karst, Alison; Drapkin, Ronny; Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. [Winter, Peter; Wood, Kris C.] Duke Univ, Durham, NC USA. [Sorrentino, Antonio; Bandyopadhyay, Sourav; Goga, Andrei] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 970 DI 10.1158/1538-7445.AM2015-970 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502016 ER PT J AU Shukla, SA Rajasagi, M Dixon, P Tiao, G Lawrence, MS Sougnez, C Brusic, V Cibulskis, K Kiezun, A Wu, CJ Getz, G AF Shukla, Sachet A. Rajasagi, Mohini Dixon, Philip Tiao, Grace Lawrence, Michael S. Sougnez, Carrie Brusic, Vladimir Cibulskis, Kristian Kiezun, Adam Wu, Catherine J. Getz, Gad TI Sensitive detection of somatic mutations in class I HLA genes reveals enrichment for functional events in cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Shukla, Sachet A.; Rajasagi, Mohini; Brusic, Vladimir; Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dixon, Philip] Iowa State Univ, Ames, IA USA. [Tiao, Grace; Lawrence, Michael S.; Sougnez, Carrie; Cibulskis, Kristian; Kiezun, Adam; Getz, Gad] Broad Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1093 DI 10.1158/1538-7445.AM2015-1093 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502135 ER PT J AU Siravegna, G Mussolin, B Buscarino, M Corti, G Cassingena, A Crisafulli, G Corcoran, RB Ponzetti, A Budillon, A Racca, P Marsoni, S Di Nicolantonio, F Loupakis, F Siena, S Bianchi, AS Bardelli, A AF Siravegna, Giulia Mussolin, Benedetta Buscarino, Michela Corti, Giorgio Cassingena, Andrea Crisafulli, Giovanni Corcoran, Ryan B. Ponzetti, Agostino Budillon, Alfredo Racca, Patrizia Marsoni, Silvia Di Nicolantonio, Federica Loupakis, Fotios Siena, Salvatore Bianchi, Andrea Sartore Bardelli, Alberto TI Blood-based molecular landscapes of resistance to EGFR blockade in colorectal cancer patients SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Siravegna, Giulia; Mussolin, Benedetta; Buscarino, Michela; Corti, Giorgio; Crisafulli, Giovanni; Marsoni, Silvia; Di Nicolantonio, Federica; Bardelli, Alberto] Candiolo Canc Inst, Candiolo, Italy. [Cassingena, Andrea; Siena, Salvatore; Bianchi, Andrea Sartore] Osped Niguarda Ca Granda, Niguarda Canc Ctr, Milan, Italy. [Corcoran, Ryan B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Ponzetti, Agostino; Racca, Patrizia] San Giovanni Battista Hosp, Med Oncol Div 1, Colorectal Canc Unit, Turin, Italy. [Budillon, Alfredo] Ist Nazl Studio & Cura Tumori Fdn Giovanni Pascal, Expt Pharmacol Unit, Naples, Italy. [Loupakis, Fotios] Azienda Osped Univ Pisana, Pisa, Italy. [Loupakis, Fotios] Univ Pisa, Pisa, Italy. RI Di Nicolantonio, Federica/A-2503-2011 OI Di Nicolantonio, Federica/0000-0001-9618-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 616 DI 10.1158/1538-7445.AM2015-616 PG 3 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501073 ER PT J AU Skates, SJ Anderson, KS Liu, T Kulasingam, V Rabideau, D Wu, CC Gillette, M Godwin, AK Urban, N Lokshin, A Marks, J Diamandis, E Zhang, Z Srivastava, S Kagan, J Patriotis, C Rodland, K AF Skates, Steven J. Anderson, Karen S. Liu, Tao Kulasingam, Vathany Rabideau, Dustin Wu, Chaochao Gillette, Michael Godwin, Andrew K. Urban, Nicole Lokshin, Anna Marks, Jeffrey Diamandis, Eleftherios Zhang, Zhen Srivastava, Sudhir Kagan, Jacob Patriotis, Christos Rodland, Karin TI Early Detection Research Network (EDRN) validation of circulating ovarian cancer biomarkers SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Skates, Steven J.; Rabideau, Dustin; Gillette, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Anderson, Karen S.] Arizona State Univ, Phoenix, AZ USA. [Liu, Tao; Wu, Chaochao; Rodland, Karin] Pacific NW Natl Lab, Richland, WA 99352 USA. [Kulasingam, Vathany; Diamandis, Eleftherios] Univ Toronto, Toronto, ON, Canada. [Gillette, Michael] Broad Inst, Cambridge, MA USA. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Urban, Nicole] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Lokshin, Anna] Univ Pittsburgh, Pittsburgh, PA USA. [Marks, Jeffrey] Duke Univ, Durham, NC USA. [Zhang, Zhen] Johns Hopkins Univ, Baltimore, MD USA. [Srivastava, Sudhir; Kagan, Jacob; Patriotis, Christos] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1570 DI 10.1158/1538-7445.AM2015-1570 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578503064 ER PT J AU Skoulidis, F Byers, L Diao, LX Papadimitrakopoulou, V Tong, P Izzo, J Behrens, C Kadara, H Parra, ER Rodriguez-Canales, J Zhang, JJ Giri, U Gudikote, J Cortez, MA Yang, C Fan, YH Peyton, M Girard, L Coombes, KR Toniatti, C Heffernan, TP Choi, M Frampton, GM Miller, V Weinstein, JN Herbst, RS Wong, KK Zhang, JH Sharma, P Mills, GM Hong, WK Minna, JD Allison, JP Futreal, A Wang, J Wistuba, I Heymach, JV AF Skoulidis, Ferdinandos Byers, Lauren Diao, Lixia Papadimitrakopoulou, Vassiliki Tong, Pan Izzo, Julie Behrens, Carmen Kadara, Humam Parra, Edwin R. Rodriguez-Canales, Jaime Zhang, Jianjun Giri, Uma Gudikote, Jayanthi Cortez, Maria Angelica Yang, Chao Fan, You Hong Peyton, Michael Girard, Luc Coombes, Kevin R. Toniatti, Carlo Heffernan, Timothy P. Choi, Murim Frampton, Garrett M. Miller, Vincent Weinstein, John N. Herbst, Roy S. Wong, Kwok-Kin Zhang, Jianhua Sharma, Padmanee Mills, Gordon M. Hong, Waun Ki Minna, John D. Allison, James P. Futreal, Andrew Wang, Jing Wistuba, Ignacio Heymach, John V. TI Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma (LUAC) with distinct biology and therapeutic vulnerabilities SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Skoulidis, Ferdinandos; Byers, Lauren; Diao, Lixia; Papadimitrakopoulou, Vassiliki; Tong, Pan; Izzo, Julie; Behrens, Carmen; Kadara, Humam; Parra, Edwin R.; Rodriguez-Canales, Jaime; Zhang, Jianjun; Giri, Uma; Gudikote, Jayanthi; Cortez, Maria Angelica; Yang, Chao; Fan, You Hong; Toniatti, Carlo; Heffernan, Timothy P.; Weinstein, John N.; Zhang, Jianhua; Sharma, Padmanee; Mills, Gordon M.; Hong, Waun Ki; Allison, James P.; Futreal, Andrew; Wang, Jing; Wistuba, Ignacio; Heymach, John V.] UT MD Anderson Canc Ctr, Houston, TX USA. [Peyton, Michael; Girard, Luc; Minna, John D.] UT Southwestern Med Ctr, Dallas, TX USA. [Coombes, Kevin R.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. [Choi, Murim] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Frampton, Garrett M.; Miller, Vincent] Fdn Med, Cambridge, MA USA. [Herbst, Roy S.] Yale Canc Ctr, Yale, CT USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 968 DI 10.1158/1538-7445.AM2015-968 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502014 ER PT J AU Soucheray, M Capelletti, M Pulido, I Kuang, YN Paweletz, CP Becker, JH Kikuchi, E Xu, CX Patel, TB Al-shahrour, F Carretero, J Wong, KK Janne, PA Shapiro, GI Shimamura, T AF Soucheray, Margaret Capelletti, Marzia Pulido, Ines Kuang, Yunan Paweletz, Cloud P. Becker, Jeffrey H. Kikuchi, Eiki Xu, Chunxiao Patel, Tarun B. Al-shahrour, Fatima Carretero, Julian Wong, Kwok-Kin Janne, Pasi A. Shapiro, Geoffrey I. Shimamura, Takeshi TI Suppression of gefitinib-induced EMT in EGFR mutant NSCLC preferentially selects for acquired T790M SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Soucheray, Margaret; Becker, Jeffrey H.; Patel, Tarun B.; Shimamura, Takeshi] Loyola Univ Chicago, Maywood, IL USA. [Capelletti, Marzia; Kuang, Yunan; Paweletz, Cloud P.; Xu, Chunxiao; Wong, Kwok-Kin; Janne, Pasi A.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pulido, Ines; Carretero, Julian] Univ Valencia, Valencia, Spain. [Kikuchi, Eiki] Hokkaido Univ, Sapporo, Hokkaido, Japan. [Al-shahrour, Fatima] Spanish Natl Canc Res Ctr, Madrid, Spain. RI Carretero, Julian/N-5214-2014 OI Carretero, Julian/0000-0001-7269-8506 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 766 DI 10.1158/1538-7445.AM2015-766 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501219 ER PT J AU Stahlhut, CE Watrud, KE Ambrico, AJ Cho, H Wang, LL Qi, J Cantley, LC Bradner, J Trotman, LC AF Stahlhut, Carlos E. Watrud, Kaitlin E. Ambrico, Alexandra J. Cho, Hyejin Wang, Lily Qi, Jun Cantley, Lewis C. Bradner, James Trotman, Lloyd C. TI Myc vs. Akt therapy in RapidCap, a GEM model for metastatic prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Stahlhut, Carlos E.; Watrud, Kaitlin E.; Ambrico, Alexandra J.; Trotman, Lloyd C.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Cho, Hyejin; Qi, Jun; Bradner, James] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wang, Lily] New York Presbyterian Hosp, New York, NY USA. [Cantley, Lewis C.] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2636 DI 10.1158/1538-7445.AM2015-2636 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505226 ER PT J AU Sullivan, J Havrda, M Paolella, B Kettenbach, A Gerber, S Israel, MA AF Sullivan, Jaclyn Havrda, Matthew Paolella, Brenton Kettenbach, Arminja Gerber, Scott Israel, Mark A. TI Phosphorylation of Id2 at the N-terminus modulates Id2 degradation and mediates cell cycle regulation in neural progenitor cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Sullivan, Jaclyn; Havrda, Matthew; Kettenbach, Arminja; Gerber, Scott; Israel, Mark A.] Geisel Sch Med Dartmouth, Lebanon, NH USA. [Paolella, Brenton] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2128 DI 10.1158/1538-7445.AM2015-2128 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504233 ER PT J AU Sun, BH Shah, B Fiskus, W Qi, J Devaraj, SGT Iyer, SP Sharma, S Bradner, JE Zu, YL Bhalla, KN AF Sun, Baohua Shah, Bhavin Fiskus, Warren Qi, Jun Devaraj, Santhana G. T. Iyer, Swaminathan P. Sharma, Sunil Bradner, James E. Zu, Youli Bhalla, Kapil N. TI BET-protein bromodomain antagonist-based combinations against ibrutinb-sensitive or resistant human Mantle Cell Lymphoma cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Sun, Baohua; Shah, Bhavin; Devaraj, Santhana G. T.; Iyer, Swaminathan P.; Zu, Youli; Bhalla, Kapil N.] Houston Methodist Res Inst, Houston, TX USA. [Fiskus, Warren] Baylor Coll Med, Houston, TX 77030 USA. [Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sharma, Sunil] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2612 DI 10.1158/1538-7445.AM2015-2612 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505203 ER PT J AU Tai, YT Acharya, C An, G Zhong, MY Feng, XY Jiang, H van Eenennaam, H van Elsas, A Munshi, NC Anderson, KC AF Tai, Yu-Tzu Acharya, Chirag An, Gang Zhong, Mike Y. Feng, Xiaoyan Jiang, Hua van Eenennaam, Hans van Elsas, Andrea Munshi, Nikhil C. Anderson, Kenneth C. TI A novel anti-a proliferation-inducing ligand hAPRIL.01A monoclonal antibody targets multiple myeloma cells in the bone marrow microenvironment SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Tai, Yu-Tzu; Acharya, Chirag; An, Gang; Zhong, Mike Y.; Feng, Xiaoyan; Jiang, Hua; Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [van Eenennaam, Hans; van Elsas, Andrea] BioNovion, Oss, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 394 DI 10.1158/1538-7445.AM2015-394 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578500374 ER PT J AU Tapias, LF Lanuti, M Ren, X Gilpin, SE Wei, L Fuchs, BC Tanabe, KK Ott, HC AF Tapias, Luis F. Lanuti, Michael Ren, Xi Gilpin, Sarah E. Wei, Lan Fuchs, Bryan C. Tanabe, Kenneth K. Ott, Harald C. TI Longitudinal monitoring of cell proliferation and cytotoxicity in a biomimetic 3D culture model for lung cancer using native extracellular matrix scaffolds SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Tapias, Luis F.; Lanuti, Michael; Ren, Xi; Gilpin, Sarah E.; Wei, Lan; Fuchs, Bryan C.; Tanabe, Kenneth K.; Ott, Harald C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 309 DI 10.1158/1538-7445.AM2015-309 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578500293 ER PT J AU Tricker, EM Xu, CX Wong, KK Janne, PA AF Tricker, Erin M. Xu, Chunxiao Wong, Kwok-Kin Janne, Pasi A. TI Efficacy of cetuximab and mutant selective EGFR inhibitor WZ4002 in EGFR T790M and non-T790M models of erlotinib resistant non-small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Tricker, Erin M.; Xu, Chunxiao; Wong, Kwok-Kin; Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2595 DI 10.1158/1538-7445.AM2015-2595 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505187 ER PT J AU Tsang, TY Mohapatra, G Itamochi, H Mok, SC Birrer, MJ AF Tsang, Tsun Yee Mohapatra, Gayatry Itamochi, Hiroaki Mok, Samuel C. Birrer, Michael J. TI Integrated genomic analysis of clear-cell ovarian cancer identifies PRKCI as a therapeutic target SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Tsang, Tsun Yee; Mohapatra, Gayatry; Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Itamochi, Hiroaki] Tottori Univ, Sch Med, Tottori 680, Japan. [Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1102 DI 10.1158/1538-7445.AM2015-1102 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578502144 ER PT J AU Tu, HC Schwitalla, S Qian, ZR LaPier, G Yermalovich, A Ku, YC Chen, SC Viswanathan, SR Zhu, H Nishihara, R Inamura, K Kim, SA Morikawa, R Mima, K Sukawa, Y Yang, JH Meredith, G Fuchs, CS Ogino, S Daley, GQ AF Tu, Ho-Chou Schwitalla, Sarah Qian, Zhirong LaPier, Grace Yermalovich, Alena Ku, Yuan-Chieh Chen, Shann-Ching Viswanathan, Srinivas R. Zhu, Hao Nishihara, Reiko Inamura, Kentaro Kim, Sun A. Morikawa, Reppi Mima, Kosuke Sukawa, Yasutaka Yang, Juhong Meredith, Gavin Fuchs, Charles S. Ogino, Shuji Daley, George Q. TI LIN28 cooperates with Wnt signaling to drive invasive intestinal and colorectal adenocarcinoma in mouse and human SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Tu, Ho-Chou; Schwitalla, Sarah; LaPier, Grace; Yermalovich, Alena; Viswanathan, Srinivas R.; Daley, George Q.] Boston Childrens Hosp, Boston, MA USA. [Qian, Zhirong; Nishihara, Reiko; Inamura, Kentaro; Kim, Sun A.; Morikawa, Reppi; Mima, Kosuke; Sukawa, Yasutaka; Yang, Juhong; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ku, Yuan-Chieh; Chen, Shann-Ching; Meredith, Gavin] Thermo Fisher Sci Inc, San Francisco, CA USA. [Zhu, Hao] Univ Texas Southwestern, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2300 DI 10.1158/1538-7445.AM2015-2300 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578504402 ER PT J AU Udayakumar, D Pandita, RK Horikoshi, N Hunt, CR Liu, QS Wong, KK Gray, NS Pandita, TK Westover, KD AF Udayakumar, Durga Pandita, Raj K. Horikoshi, Nobuo Hunt, Clayton R. Liu, Qingsong Wong, Kwok-Kin Gray, Nathanael S. Pandita, Tej K. Westover, Kenneth D. TI Torin2 suppresses ionizing radiation induced DNA damage repair SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Udayakumar, Durga; Pandita, Raj K.; Horikoshi, Nobuo; Hunt, Clayton R.; Pandita, Tej K.] Houston Methodist Res Inst, Houston, TX USA. [Liu, Qingsong; Gray, Nathanael S.] Harvard Univ, Sch Med, Boston, MA USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Westover, Kenneth D.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2852 DI 10.1158/1538-7445.AM2015-2852 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505435 ER PT J AU Urba, WJ Martin-Algarra, S Callahan, M Wolchok, JD Sharfman, WH Sosman, JA Bhatia, S Hwu, WJ Gajewski, TF Slingluff, CL Shen, Y Horak, CE Hodi, FS AF Urba, Walter J. Martin-Algarra, Salvador Callahan, Margaret Wolchok, Jedd D. Sharfman, William H. Sosman, Jeffrey A. Bhatia, Shailender Hwu, Wen-Jen Gajewski, Thomas F. Slingluff, Craig L. Shen, Yun Horak, Christine E. Hodi, F. Stephen TI Immunomodulatory activity of nivolumab monotherapy in patients with advanced melanoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Urba, Walter J.] Providence Canc Ctr, Earle A Chiles Res Inst, Portland, OR USA. [Martin-Algarra, Salvador] Univ Navarra, E-31080 Pamplona, Spain. [Callahan, Margaret; Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sharfman, William H.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Bhatia, Shailender] Univ Washington, Seattle, WA 98195 USA. [Hwu, Wen-Jen] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gajewski, Thomas F.] Univ Chicago, Gordon Ctr Integrat Sci, Chicago, IL 60637 USA. [Slingluff, Craig L.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Shen, Yun; Horak, Christine E.] Bristol Myers Squibb, Princeton, NJ USA. [Hodi, F. Stephen] Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2855 DI 10.1158/1538-7445.AM2015-2855 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578506002 ER PT J AU Varadan, V Miskimen, KLS Parsai, S Krop, IE Winer, EP Bossuyt, V Abu-Khalaf, M Sikov, W Harris, LN AF Varadan, Vinay Miskimen, Kristy L. S. Parsai, Shikha Krop, Ian E. Winer, Eric P. Bossuyt, Veerle Abu-Khalaf, Maysa Sikov, William Harris, Lyndsay N. TI A discovery and validation set of breast cancer preoperative clinical trials show an increase in immune score upon brief-exposure to trastuzumab (T) and the HER2-enriched subtype predict response to combination chemotherapy and T SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Varadan, Vinay; Miskimen, Kristy L. S.; Parsai, Shikha] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Krop, Ian E.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bossuyt, Veerle; Abu-Khalaf, Maysa] Yale Univ, New Haven, CT USA. [Sikov, William] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Harris, Lyndsay N.] Univ Hosp Cleveland, Seidman Canc Ctr, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2836 DI 10.1158/1538-7445.AM2015-2836 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505419 ER PT J AU Wilson, TR Savage, H Aimi, J Jin, J Parmar, H Hsu, J Krop, I Saura, C Cervantes, A Sachdev, J Patel, M Cejalvo, J Oliveira, M Winer, E Von Hoff, D Baselga, J Juric, D AF Wilson, Timothy R. Savage, Heidi Aimi, Junko Jin, Jessica Parmar, Hema Hsu, Jerry Krop, Ian Saura, Cristina Cervantes, Andres Sachdev, Jasgit Patel, Manish Cejalvo, Juan Oliveira, Mafalda Winer, Eric Von Hoff, Daniel Baselga, Jose Juric, Dejan TI Circulating tumor DNA (ctDNA) analysis of PIK3CA and AKT1 mutations in patients enrolled onto the Phase 1b study of the PI3K inhibitor taselisib (GDC-0032) in solid malignancies SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Wilson, Timothy R.; Savage, Heidi; Aimi, Junko; Jin, Jessica; Parmar, Hema; Hsu, Jerry] Genentech Inc, San Francisco, CA 94080 USA. [Krop, Ian; Winer, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Saura, Cristina; Oliveira, Mafalda] Vall dHebron Univ Hosp, Barcelona, Spain. [Cervantes, Andres; Cejalvo, Juan] Inst Hlth Res INCLI VA, Valencia, Spain. [Sachdev, Jasgit; Von Hoff, Daniel] Virginia G Piper Canc Ctr TGen, Scottsdale, AZ USA. [Patel, Manish] Sarah Cannon Res Inst, Sarasota, FL USA. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Juric, Dejan] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2399 DI 10.1158/1538-7445.AM2015-2399 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578505001 ER PT J AU Yamamura, S Mitsui, Y Bucay, N Saini, S Majid, S Deng, GR Shahryary, V Dahiya, R Tanaka, Y AF Yamamura, Soichiro Mitsui, Yozo Bucay, Nathan Saini, Sharanjot Majid, Shahana Deng, Guoren Shahryary, Varahram Dahiya, Rajvir Tanaka, Yuichiro TI RNA-Seq profiling of silibinin effects on bladder cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Yamamura, Soichiro; Mitsui, Yozo; Bucay, Nathan; Saini, Sharanjot; Majid, Shahana; Deng, Guoren; Shahryary, Varahram; Dahiya, Rajvir; Tanaka, Yuichiro] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 902 DI 10.1158/1538-7445.AM2015-902 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578501353 ER PT J AU Yanagita, M Luke, JJ Paweletz, CP Ivanova, E Kirschmeier, PT Hodi, SF Janne, PA AF Yanagita, Masahiko Luke, Jason J. Paweletz, Cloud P. Ivanova, Elena Kirschmeier, Paul T. Hodi, Stephen F. Jaenne, Pasi A. TI Isolation and characterization of circulating melanoma cells by size filtration and fluorescent in situ hybridization SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Yanagita, Masahiko; Paweletz, Cloud P.; Ivanova, Elena; Kirschmeier, Paul T.; Hodi, Stephen F.; Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Luke, Jason J.] Univ Chicago Med, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 1598 DI 10.1158/1538-7445.AM2015-1598 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578503091 ER PT J AU Zheng, S Cherniack, AD Dewal, N Moffitt, RA Danilova, L Murray, BA Lerario, AM Else, T Knijnenburg, TA Ciriello, G Kim, S Assie, G Morozova, O Akbani, R Shih, J Hoadley, KA Choueiri, TK Choueiril, TK Mete, O Robertson, GA Meyerson, M Demeure, MJ Beuschlein, F Gill, A Latronico, AC Fragosa, MC Cope, L Kebebew, E Habra, MA Whitsett, TG Bussey, KJ Rainey, WE Asa, S Bertherat, J Fassnacht, M Wheeler, DA Hammer, GD Giordano, TJ Verhaak, R AF Zheng, Siyuan Cherniack, Andrew D. Dewal, Ninad Moffitt, Richard A. Danilova, Ludmila Murray, Bradley A. Lerario, Antonio M. Else, Tobias Knijnenburg, Theo A. Ciriello, Giovanni Kim, Seungchan Assie, Guillaume Morozova, Olena Akbani, Rehan Shih, Juliann Hoadley, Katherine A. Choueiri, Toni K. Waldmann, Jens Mete, Ozgur Robertson, Gordon A. Meyerson, Matthew Demeure, Michael J. Beuschlein, Felix Gill, Anthony Latronico, Ana C. Fragosa, Maria C. Cope, Leslie Kebebew, Electron Habra, Mouhammed A. Whitsett, Timothy G. Bussey, Kimberly J. Rainey, William E. Asa, Sylvia Bertherat, Jerome Fassnacht, Martin Wheeler, David A. Hammer, Gary D. Giordano, Thomas J. Verhaak, Roel CA Canc Genome Atlas Res Network TI Comprehensive Pan-Genomic characterization of adrenocortical carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Zheng, Siyuan; Akbani, Rehan; Habra, Mouhammed A.; Verhaak, Roel] UT MD Anderson Canc Ctr, Houston, TX USA. [Cherniack, Andrew D.; Murray, Bradley A.; Shih, Juliann] Broad Inst Harvard & MIT, Cambridge, MA USA. [Dewal, Ninad; Wheeler, David A.] Baylor Coll Med, Houston, TX 77030 USA. [Moffitt, Richard A.; Hoadley, Katherine A.] Univ N Carolina, Chapel Hill, NC USA. [Danilova, Ludmila; Cope, Leslie] Johns Hopkins Univ, Baltimore, MD USA. [Lerario, Antonio M.; Else, Tobias; Rainey, William E.; Hammer, Gary D.; Giordano, Thomas J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Knijnenburg, Theo A.] Inst Syst Biol, Seattle, WA USA. [Ciriello, Giovanni] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kim, Seungchan; Demeure, Michael J.; Whitsett, Timothy G.; Bussey, Kimberly J.] Translat Genom Res Inst, Phoenix, AZ USA. [Assie, Guillaume; Bertherat, Jerome] Inst Cochin Genet Mol, F-75014 Paris, France. [Morozova, Olena] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. [Choueiri, Toni K.; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Waldmann, Jens] Univ Hosp Marburg, Marburg, Germany. [Mete, Ozgur; Asa, Sylvia] Univ Hlth Network, Toronto, ON, Canada. [Robertson, Gordon A.] Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. [Beuschlein, Felix] Univ Munich, Munich, Germany. [Gill, Anthony] Univ Sydney, Sydney, NSW 2006, Australia. [Latronico, Ana C.; Fragosa, Maria C.] Univ Sao Paulo, Sao Paulo, Brazil. [Kebebew, Electron] NCI, Bethesda, MD 20892 USA. [Fassnacht, Martin] Univ Hosp Wuerzburg, Wurzburg, Germany. NR 0 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 2976 DI 10.1158/1538-7445.AM2015-2976 PG 2 WC Oncology SC Oncology GA DF8AH UT WOS:000371578506120 ER PT J AU Zimmerman, MW He, SN Shin, J Zhu, SZ Mansour, M Joung, K Quan, JH Yusufzai, T Look, AT AF Zimmerman, Mark W. He, Shuning Shin, Jimann Zhu, Shizhen Mansour, Marc Joung, Keith Quan, Jinhua Yusufzai, Timur Look, A. Thomas TI Loss of chd5-mediated tumor suppression accelerates MYCN-driven neuroblastoma tumorigenesis in zebrafish SO CANCER RESEARCH LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Zimmerman, Mark W.; He, Shuning; Shin, Jimann; Zhu, Shizhen; Mansour, Marc; Quan, Jinhua; Yusufzai, Timur; Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joung, Keith] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 SU 15 MA 476 DI 10.1158/1538-7445.AM2015-476 PG 1 WC Oncology SC Oncology GA DF8AH UT WOS:000371578500454 ER PT J AU Song, ZR Chopra, V McMahon, LF AF Song, Zirui Chopra, Vineet McMahon, Laurence F., Jr. TI Addressing the Primary Care Workforce Crisis SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Editorial Material ID ECONOMICS AB Our nation's primary care system is in crisis. As medical homes and accountable care organizations increasingly rely on a strong primary care workforce, the shortage of primary care physicians now calls for more policy attention and urgency. In the spirit of the 2014 Institute of Medicine recommendations on graduate medical education (GME) funding, we propose that CMS explicitly reward teaching hospitals if a certain share of their graduates (we propose 30%) remain in primary care 3 years after residency, either through additional payments or release of a withhold. Such a policy could allow hospitals to retain GME funding at a time when continued federal subsidization of GME is being called into question. Moreover, hospitals stand to benefit from producing primary care physicians, both under traditional fee-for-service contracts that reward volume through referrals and, especially, under risk contracts that reward for greater numbers of covered lives. C1 [Song, Zirui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chopra, Vineet; McMahon, Laurence F., Jr.] Univ Michigan Hlth Syst, Dept Med, Div Gen Internal Med, Ann Arbor, MI USA. RP McMahon, LF (reprint author), 2800 Plymouth Rd,Bldg 16,Rm 430W, Ann Arbor, MI 48109 USA. EM lmcmahon@umich.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD AUG PY 2015 VL 21 IS 8 BP E452 EP E454 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DD4AF UT WOS:000369864000001 PM 26618225 ER PT J AU Volpp, KG Troxel, AB Long, JA Ibrahim, SA Appleby, D Smith, JO Jaskowiak, J Helweg-Larsen, M Doshi, JA Kimmel, SE AF Volpp, Kevin G. Troxel, Andrea B. Long, Judith A. Ibrahim, Said A. Appleby, Dina Smith, J. Otis Jaskowiak, Jane Helweg-Larsen, Marie Doshi, Jalpa A. Kimmel, Stephen E. TI A Randomized Controlled Trial of Co-Payment Elimination: The CHORD Trial SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID INSURANCE DESIGN PROGRAM; CORONARY-HEART-DISEASE; MEDICATION ADHERENCE; BLOOD-PRESSURE; LONG-TERM; STATIN THERAPY; MYOCARDIAL-INFARCTION; COPAYMENT INCREASE; PRESCRIPTION DRUGS; ELDERLY PATIENTS AB Objectives: Efforts to improve adherence by reducing co-payments through value-based insurance design are become more prevalent despite limited evidence of improved health outcomes. The objective of this study was to determine whether eliminating patient co-payments for blood pressure medications improves blood pressure control. Study Design: Randomized controlled trial. Methods: The Collaboration to Reduce Disparities in Hypertension (CHORD) was a randomized controlled trial with 12 months' follow-up conducted among patients from the Philadelphia and Pittsburgh Veterans Administration Medical Centers. We enrolled 479 patients with poorly controlled systolic blood pressure. Participants were randomly assigned to: a) receive reductions in co-payments from $8 to $0 per medication per month for each antihypertensive prescription filled, b) a computerized behavioral intervention (CBI), c) both co-pay reduction and CBI, or d) usual care. Our main outcome measure was change in systolic blood pressure from enrollment to 12 months post enrollment. We also measured adherence using the medication possession ratio in a subset of participants. Results: There were no significant interactions between the co-payment interventions and the CBI interventions. There was no relative difference in the change in medication possession ratio between baseline and 12 months (0.05% and 0.90% in control and incentive groups, respectively; P = .74) or in continuous medication gaps of 30, 60, or 90 days. Blood pressure decreased among all participants, but to a similar degree between the financial incentive and control groups. Systolic pressure within the incentive group dropped 13.2 mm Hg versus 15.2 mm Hg for the control group (difference = 2.0; 95% CI, -2.3 to 6.3; P = .36). The proportion of patients with blood pressure under control at 12 months was 29.5% in the incentive group versus 33.9 in the control group (odds ratio, 0.8; 95% CI, 0.5-1.3; P = .36). Conclusions: Among patients with poorly controlled blood pressure, financial incentives as implemented in this trial that reduced patient cost sharing for blood pressure medications did not improve medication adherence or blood pressure control. C1 [Volpp, Kevin G.; Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Volpp, Kevin G.; Troxel, Andrea B.; Long, Judith A.; Kimmel, Stephen E.] Penn CMU Roybal P30 Ctr Behav Econ & Hlth, Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Philadelphia, PA USA. [Volpp, Kevin G.; Long, Judith A.; Doshi, Jalpa A.; Kimmel, Stephen E.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kimmel, Stephen E.] Univ Penn, Ctr Therapeut Effectiveness Res, Perelman Sch Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Troxel, Andrea B.; Appleby, Dina; Jaskowiak, Jane; Kimmel, Stephen E.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Pittsburgh Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Smith, J. Otis] Cheyney Univ, Dept Psychol, Cheyney, PA USA. [Helweg-Larsen, Marie] Dickinson Coll, Dept Psychol, Carlisle, PA 17013 USA. RP Volpp, KG (reprint author), Univ Penn, Leonard Davis Inst Ctr Hlth Incent & Behav Econ, Perelman Sch Med, 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.; Volpp, KG (reprint author), Univ Penn, Wharton Sch, 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu NR 58 TC 2 Z9 2 U1 2 U2 2 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD AUG PY 2015 VL 21 IS 8 BP E455 EP U16 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DD4AF UT WOS:000369864000002 PM 26618226 ER PT J AU Volpp, KG Troxel, AB Long, JA Ibrahim, SA Appleby, D Smith, JO Doshi, JA Jaskowiak, J Helweg-Larsen, M Kimmel, SE AF Volpp, Kevin G. Troxel, Andrea B. Long, Judith A. Ibrahim, Said A. Appleby, Dina Smith, J. Otis Doshi, Jalpa A. Jaskowiak, Jane Helweg-Larsen, Marie Kimmel, Stephen E. TI A Randomized Controlled Trial of Negative Co-Payments: The CHORD Trial SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CORONARY-HEART-DISEASE; MEDICATION ADHERENCE; INSURANCE DESIGN; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; COPAYMENT INCREASE; PRESCRIPTION DRUGS; LONG-TERM; BENEFITS; HYPERTENSION AB Objectives: Value-based insurance designs are being widely used. We undertook this study to examine whether a financial incentive that lowered co-payments for blood pressure medications below $0 improved blood pressure control among patients with poorly controlled hypertension. Study Design: Randomized controlled trial. Methods: Participants from 3 Pennsylvania hospitals (n = 337) were randomly assigned to: a) be paid $8 per medication per month for filling blood pressure prescriptions, b) a computerized behavioral intervention (CBI), c) both payment and CBI, or d) usual care. The primary outcome was change in blood pressure between baseline and 12 months post enrollment. We also measured adherence using the medication possession ratio in a subset of participants. Results: There were no significant interactions between the incentive and the CBI interventions. There were no significant changes in medication possession ratio in the treatment group. Blood pressure decreased among all participants, but to a similar degree between the financial incentive and control groups. Systolic blood pressure (SBP) dropped 13.7 mm Hg for the incentive group versus 10.0 mm Hg for the control group (difference = -3.7; 95% CI, -9.0 to 1.6; P = .17). The proportion of patients with blood pressure under control 12 months post enrollment was 35.6% of the incentive group versus 27.7% of the control group (odds ratio, 1.4; 95% CI, 0.8-2.5; P = .19). Diabetics in the incentive group had an average drop in SBP of 12.7 mm Hg between baseline and 12 months compared with 4.0 mm Hg in the control group (P = .02). Patients in the incentive group without diabetes experienced average SBP reductions of 15.0 mm Hg, compared with 16.3 mm Hg for control group nondiabetics (P = .71). Conclusions: Among patients with poorly controlled blood pressure, financial incentives as implemented in this trial did not improve blood pressure control or adherence except among patients with diabetes. C1 [Volpp, Kevin G.; Long, Judith A.; Ibrahim, Said A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Volpp, Kevin G.; Troxel, Andrea B.; Doshi, Jalpa A.; Kimmel, Stephen E.] Penn CMU Roybal P30 Ctr Behav Econ & Hlth, Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Philadelphia, PA USA. [Volpp, Kevin G.; Long, Judith A.; Ibrahim, Said A.; Doshi, Jalpa A.; Kimmel, Stephen E.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kimmel, Stephen E.] Univ Penn, Ctr Therapeut Effectiveness Res, Perelman Sch Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Troxel, Andrea B.; Appleby, Dina; Jaskowiak, Jane; Kimmel, Stephen E.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Troxel, Andrea B.; Appleby, Dina; Jaskowiak, Jane; Kimmel, Stephen E.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Pittsburgh Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Smith, J. Otis] Cheyney Univ, Dept Psychol, Cheyney, PA USA. [Helweg-Larsen, Marie] Dickinson Coll, Dept Psychol, Carlisle, PA 17013 USA. RP Volpp, KG (reprint author), Univ Penn, Perelman Sch Med, Ctr Hlth Incent & Behav Econ, Leonard Davis Inst, 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.; Volpp, KG (reprint author), Univ Penn, Wharton Sch, 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu NR 40 TC 0 Z9 0 U1 1 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD AUG PY 2015 VL 21 IS 8 BP E465 EP U26 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DD4AF UT WOS:000369864000003 PM 26625506 ER PT J AU Sacks, NC Burgess, JF Cabral, HJ McDonnell, ME Pizer, SD AF Sacks, Naomi C. Burgess, James F., Jr. Cabral, Howard J. McDonnell, Marie E. Pizer, Steven D. TI The Effects of Cost Sharing on Adherence to Medications Prescribed for Concurrent Use: Do Definitions Matter? SO JOURNAL OF MANAGED CARE & SPECIALTY PHARMACY LA English DT Article ID CHRONIC DISEASE SCORE; AUTOMATED PHARMACY DATA; LIPID-LOWERING THERAPY; DIABETES-MELLITUS; RISK ADJUSTMENT; DRUG BENEFITS; CLAIMS DATA; COULD SAVE; NONADHERENCE; OUTCOMES AB BACKGROUND: Accurate estimates of the effects of cost sharing on adherence to medications prescribed for use together, also called concurrent adherence, are important for researchers, payers, and policymakers who want to reduce barriers to adherence for chronic condition patients prescribed multiple medications concurrently. But measure definition consensus is lacking, and the effects of different definitions on estimates of cost-related nonadherence are unevaluated. OBJECTIVES: To (a) compare estimates of cost-related nonadherence using different measure definitions and (b) provide guidance for analyses of the effects of cost sharing on concurrent adherence. METHODS: This is a retrospective cohort study of Medicare Part D beneficiaries aged 65 years and older who used multiple oral antidiabetics concurrently in 2008 and 2009. We compared patients with standard coverage, which contains cost-sharing requirements in deductible (100%), initial (25%), and coverage gap (100%) phases, to patients with a low-income subsidy (US) and minimal cost-sharing requirements. Data source was the IMS Health Longitudinal Rescription Database. Patients with standard coverage were propensity matched to controls with US coverage. Propensity score was developed using logistic regression to model likelihood of Part D standard enrollment, controlling for sociodemographic and health status characteristics. For analysis, 3 definitions were used for unadjusted and adjusted estimates of adherence: (1) patients adherent to All medications; (2) patients adherent on Average; and (3) patients adherent to My medication. Analyses were conducted using the full study sample and then repeated in analytic subgroups where patients used (a) 1 or more costly branded oral antidiabetics or (b) inexpensive generics only. RESULTS: We identified 12,771 propensity matched patients with Medicare Part D standard (N=6,298) or US (N=6,473) coverage who used oral antidiabetics in 2 or more of the same classes in 2008 and 2009. In this sample, estimates of the effects of cost sharing on concurrent adherence varied by measure definition, coverage type, and proportion of patients using more costly branded drugs. Adherence rates ranged from 37% (All: standard patients using 1+ branded) to 97% (My: US using generics only). In adjusted estimates, standard patients using branded drugs had 0.63 (95% 0 = 0.57-0.70) and 0.70 (95% a= 0.63-0.77) times the odds of concurrent adherence using All and Average definitions, respectively. The My subgroup was not significant (CR= 0.89, 95%0=0.87-1.17). Estimates also varied in the full -study sample (All: CRr 0.79, 95%0= 0.74-0.85; Average: CR= 0.83, 95% a= 0.77-0.89) and generics -only subgroup, although cost sharing effects were smaller. The My subgroup generated no significant estimates. CONCLUSIONS: Dfferent concurrent adherence measure definitions lead to markedly different findings of the effects of cost sharing on concurrent adherence, with All and Average subgroups sensitive to thcsc effects. However, when more study patients use inexpensive generics, estimates of these effects on adherence to branded medications with higher cost sharing requirements may be diluted. When selecting a measure definition, researchers, payers, and policy analysts should consider the range of medication prices patients face, use a measure sensitive to the effects of cost sharing on adherence, and perform subgroup analyses for patients prescribed more medications for which they must pay more, since these patients are most vulnerable to cost-related nonadherence. C1 [Sacks, Naomi C.] Precis Value, 55 Cambridge Pkwy,Ste 300E, Cambridge, MA 02142 USA. [Cabral, Howard J.] Boston Univ, Sch Publ Hlth, Dept Stat, Boston, MA USA. [McDonnell, Marie E.] Brigham & Womens Hosp, Brigham & Womens Diabet Program, Boston, MA 02115 USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Burgess, James F., Jr.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Pizer, Steven D.] VA Boston Healthcare Syst, Healthcare Financing & Econ, Boston, MA USA. [Pizer, Steven D.] Northeastern Univ, Dept Pharm Practice, Sch Pharm, Boston, MA 02115 USA. [Pizer, Steven D.] Northeastern Univ, Dept Econ, Boston, MA 02115 USA. RP Sacks, NC (reprint author), Precis Value, 55 Cambridge Pkwy,Ste 300E, Cambridge, MA 02142 USA. EM naomi.sacks@precisionformedicine.com NR 45 TC 1 Z9 1 U1 1 U2 2 PU ACAD MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 2376-0540 EI 2376-1032 J9 J MANAG CARE SPEC PH JI J. Manag. Care Spec. Pharm. PD AUG PY 2015 VL 21 IS 8 BP 678 EP U114 PG 12 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA DC4KY UT WOS:000369191000006 PM 26233540 ER PT J AU McCarthy, AM Yamartino, P Yang, JN Bristol, M Conant, EF Armstrong, K AF McCarthy, Anne Marie Yamartino, Philip Yang, Jianing Bristol, Mirar Conant, Emily F. Armstrong, Katrina TI Racial Differences in False-positive Mammogram Rates Results From the ACRIN Digital Mammographic Imaging Screening Trial (DMIST) SO MEDICAL CARE LA English DT Article DE mammography; false positive; race; black; African American ID ACUTE MYOCARDIAL-INFARCTION; SERVING VULNERABLE WOMEN; BREAST-RELATED CARE; DIAGNOSTIC MAMMOGRAPHY; TECHNOLOGY DIFFUSION; FACILITY CHARACTERISTICS; AMERICAN-COLLEGE; CERVICAL-CANCER; BLACK PATIENTS; WHITE WOMEN AB Background: Mammography screening reduces breast cancer mortality, but false-positive tests are common. Few studies have assessed racial differences in false-positive rates. Objectives: We compared false-positive mammography rates for black and white women, and the effect of patient and facility characteristics on false positives. Research Design and Subjects: A prospective cohort study. From a sample of the American College of Radiology Imaging Network (ACRIN) Digital Mammographic Imaging Screening Trial (DMIST), we identified black/African American (N= 3176) or white (N= 26,446) women with no prior breast surgery or breast cancer. Measures: Race, demographics, and breast cancer risk factors were self-reported. Results of initial digital and film mammograms were assessed. False positives were defined as a positive mammogram (Breast Imaging Reporting and Data System category 0, 4, 5) with no cancer diagnosis within 15 months. Results: The false-positive rate for digital mammograms was 9.2% for black women compared with 7.8% for white women (P = 0.009). After adjusting for age, black women had 17% increased odds of false-positive digital mammogram compared with whites (OR = 1.17; 95% CI, 1.01-1.35; P = 0.033). This association was attenuated after adjusting for patient factors, prior films, and study site (OR = 1.04; 95% CI, 0.91-1.20; P = 0.561). There was no difference in the occurrence of false positives by race for film mammography. Conclusions: Black women had higher frequency of false-positive digital mammograms explained by lack of prior films and study site. The variation in the disparity between the established technique (film) and the new technology (digital) raises the possibility that racial differences in screening quality may be greatest for new technologies. C1 [McCarthy, Anne Marie; Bristol, Mirar; Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [McCarthy, Anne Marie; Bristol, Mirar; Armstrong, Katrina] Harvard Univ, Sch Med, Boston, MA USA. [Yamartino, Philip; Yang, Jianing] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Conant, Emily F.] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP McCarthy, AM (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,940F, Boston, MA 02114 USA. EM amccarthy8@partners.org FU National Institutes of Health/National Cancer Institute [U54 CA163313] FX Supported by a grant from the National Institutes of Health/National Cancer Institute U54 CA163313: Population-Based Research Optimizing Screening through Personalized Regimens. NR 49 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD AUG PY 2015 VL 53 IS 8 BP 673 EP 678 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DD0UR UT WOS:000369636000004 PM 26125419 ER PT J AU Lo-Ciganic, WH Donohue, JM Thorpe, JM Perera, S Thorpe, CT Marcum, ZA Gellad, WF AF Lo-Ciganic, Wei-Hsuan Donohue, Julie M. Thorpe, Joshua M. Perera, Subashan Thorpe, Carolyn T. Marcum, Zachary A. Gellad, Walid F. TI Using Machine Learning to Examine Medication Adherence Thresholds and Risk of Hospitalization SO MEDICAL CARE LA English DT Article DE medication adherence; diabetes; machine learning; survival tree; classification and regression tree ID RANDOM SURVIVAL FORESTS; HEALTH-CARE; DIABETES-MELLITUS; HEART-FAILURE; CLAIMS DATA; COSTS; NONADHERENCE; ASSOCIATION; MORTALITY; POPULATION AB Background: Quality improvement efforts are frequently tied to patients achieving >= 80% medication adherence. However, there is little empirical evidence that this threshold optimally predicts important health outcomes. Objective: To apply machine learning to examine how adherence to oral hypoglycemic medications is associated with avoidance of hospitalizations, and to identify adherence thresholds for optimal discrimination of hospitalization risk. Methods: A retrospective cohort study of 33,130 non-dual-eligible Medicaid enrollees with type 2 diabetes. We randomly selected 90% of the cohort (training sample) to develop the prediction algorithm and used the remaining (testing sample) for validation. We applied random survival forests to identify predictors for hospitalization and fit survival trees to empirically derive adherence thresholds that best discriminate hospitalization risk, using the proportion of days covered (PDC). Outcomes: Time to first all-cause and diabetes-related hospitalization. Results: The training and testing samples had similar characteristics (mean age, 48 y; 67% female; mean PDC = 0.65). We identified 8 important predictors of all-cause hospitalizations (rank in order): prior hospitalizations/emergency department visit, number of prescriptions, diabetes complications, insulin use, PDC, number of prescribers, Elixhauser index, and eligibility category. The adherence thresholds most discriminating for risk of all-cause hospitalization varied from 46% to 94% according to patient health and medication complexity. PDC was not predictive of hospitalizations in the healthiest or most complex patient subgroups. Conclusions: Adherence thresholds most discriminating of hospitalization risk were not uniformly 80%. Machine-learning approaches may be valuable to identify appropriate patient-specific adherence thresholds for measuring quality of care and targeting nonadherent patients for intervention. C1 [Lo-Ciganic, Wei-Hsuan; Donohue, Julie M.; Thorpe, Joshua M.; Thorpe, Carolyn T.; Marcum, Zachary A.; Gellad, Walid F.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Pittsburgh, PA USA. [Lo-Ciganic, Wei-Hsuan] Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Tucson, AZ 85721 USA. [Donohue, Julie M.] Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Thorpe, Joshua M.; Thorpe, Carolyn T.] Univ Pittsburgh, Dept Pharm & Therapeut, Sch Pharm, Pittsburgh, PA USA. [Thorpe, Joshua M.; Thorpe, Carolyn T.; Gellad, Walid F.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Perera, Subashan] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Perera, Subashan; Marcum, Zachary A.; Gellad, Walid F.] Univ Pittsburgh, Dept Med, Sch Pharm, Pittsburgh, PA 15261 USA. [Marcum, Zachary A.] Univ Washington, Sch Pharm, Dept Pharm, Seattle, WA 98195 USA. RP Lo-Ciganic, WH (reprint author), Univ Arizona, Dept Pharm Practice & Sci, Coll Pharm, POB 210202,Drachman Hall Room 306K,1295N Martin A, Tucson, AZ 85719 USA. EM lociganic@pharmacy.arizona.edu OI Donohue, Julie/0000-0003-2418-6017 FU University of Pittsburgh Health Policy Institute, Center for Pharmaceutical Policy and Prescribing; VA HSR&D Career Development Award; Pittsburgh Claude D. Pepper Older Americans Independence Center (NIA) [P30 AGAG024827] FX W.-H.L.-C. was funded by a post-doctoral fellowship through the University of Pittsburgh Health Policy Institute, Center for Pharmaceutical Policy and Prescribing. W.F.G. is supported by a VA HSR&D Career Development Award. W.F.G. has previously served as a consultant to IMS health on the topic of medication adherence and serves as an unpaid member of the Board of Advisors for HealthPrize. S.P. is supported by the Pittsburgh Claude D. Pepper Older Americans Independence Center (NIA P30 AGAG024827). NR 49 TC 3 Z9 3 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD AUG PY 2015 VL 53 IS 8 BP 720 EP 728 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DD0UR UT WOS:000369636000011 PM 26147866 ER PT J AU Freeman, MP McInerney, K Sosinsky, AZ Kwiatkowski, MA Cohen, LS AF Freeman, Marlene P. McInerney, Kathryn Sosinsky, Alexandra Z. Kwiatkowski, Molly A. Cohen, Lee S. TI Omega-3 fatty acids for atypical antipsychotic-associated hypertriglyceridemia SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article ID CARDIOVASCULAR-DISEASE; MENTAL-ILLNESS; SCHIZOPHRENIA; MORTALITY; RISK; SWEDEN; LIPIDS; TRENDS AB BACKGROUND: The objective of this open-label, preliminary study was to assess the efficacy of omega-3 fatty acids for treating dyslipidemia associated with use of atypical antipsychotics. METHODS: Participants treated with atypical antipsychotics who had hypertriglyceridemia (>200 mg/dL) and/or hypercholesterolemia (>250 mg/dL) were enrolled in an open trial and received omega-3 fatty acids (Lovaza) for up to 16 weeks. Serum lipid profiles were re-assessed at 8 and 16 weeks. RESULTS: Twenty-eight participants with dyslipidemia enrolled in the trial; 16 were evaluable with post-baseline assessments. There was an average decrease in triglyceride levels of 54.13 +/- 83.44 mg/dL (P=.04). A more pronounced benefit of omega-3 supplementation was observed in participants with elevated triglyceride levels at baseline (>200 mg/dL), compared with those with elevated cholesterol values but normal or more modestly elevated triglyceride levels at enrollment. Participants with hypertriglyceridemia at baseline (n = 10, >200 mg/dL) experienced a mean decrease in triglyceride levels of 75.8 +/- 28.71 mg/dL, a significantly larger decrease than was observed among all participants (P=.005). CONCLUSIONS: Omega-3 supplementation reduced triglyceride levels but not levels of total cholesterol. Recruitment and retention in this study was challenging, and could indicate a lack of screening for dyslipidemia among atypical antipsychotic users/prescribers or could reflect the overthe-counter availability of omega-3 fatty acids. C1 [Freeman, Marlene P.; McInerney, Kathryn; Sosinsky, Alexandra Z.; Kwiatkowski, Molly A.; Cohen, Lee S.] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. RP Freeman, MP (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM mfreeman@partners.org FU GlaxoSmithKline FX This work was supported by GlaxoSmithKline who provided Lovaza capsules for study use and financial support of an investigator initiated trial. We would like to thank the participants who volunteered their time. We would also like to thank Dr. Joseph Hibbeln for his thoughtful comments regarding data analysis. NR 25 TC 1 Z9 1 U1 2 U2 2 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 1040-1237 EI 1547-3325 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD AUG PY 2015 VL 27 IS 3 BP 197 EP 202 PG 6 WC Psychiatry SC Psychiatry GA DC6SM UT WOS:000369349900006 PM 26247219 ER PT J AU Shim, HS Mari-Kenudson Zheng, ZL Liebers, M Cha, YJ Ho, QH Onozato, M Le, LP Heist, RS Iafrate, AJ AF Shim, Hyo Sup Mari-Kenudson Zheng, Zongli Liebers, Matthew Cha, Yoon Jin Ho, Quan Hoang Onozato, Maristela Le, Long Phi Heist, Rebecca S. Iafrate, A. John TI Unique Genetic and Survival Characteristics of Invasive Mucinous Adenocarcinoma of the Lung SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung; Adenocarcinoma; Mucinous; Mutation; Gene fusion; Targeted therapy ID RESPIRATORY SOCIETY CLASSIFICATION; INTERNATIONAL ASSOCIATION; MUTATIONAL ANALYSIS; CANCER GENOMICS; REARRANGEMENTS; FUSIONS; SENSITIVITY; INHIBITION; CARCINOMAS; GEFITINIB AB Introduction: Invasive mucinous adenocarcinoma is a unique histologic subtype of lung cancer, and our knowledge of its genetic and clinical characteristics is rapidly evolving. Here, we present next-generation sequencing analysis of nucleotide variant and fusion events along with clinical follow-up in a series of lung mucinous adenocarcinoma. Methods: We collected 72 mucinous adenocarcinomas from the United States and Korea. All had been previously assessed for KRAS and EGFR mutations. For KRAS wild-type cases (n = 30), we performed deep targeted next-generation sequencing for gene fusions and nucleotide variants and correlated survival and other clinical features. Results: As expected, KRAS mutations were the most common alteration found (63% of cases); however, the distribution of nucleotide position alterations was more similar to that observed in gastrointestinal tumors than other lung tumors. Within the KRAS-negative cases, we found numerous potentially targetable gene fusions and mutations, including CD74-NRG1, VAMP2-NRG1, TRIM4-BRAF, TPM3-NTRK1, and EML4-ALK gene fusions and ERBB2, BRAF, and PIK3CA mutations. Unexpectedly, we found only two cases with TP53 mutation, which is much lower than observed in lung adenocarcinomas in general. The overall mutation burden was low in histologically confirmed mucinous adenocarcinomas from the public The Cancer Genome Atlas exome data set, regardless of smoking history, suggesting a link between TP53 status and mutation burden in mucinous tumors. There was no significant difference for recurrence-free survival between stagematched mucinous and nonmucinous adenocarcinomas. It was notable that all recurrence sites were in the lungs for completely resected cases. Conclusions: Our data suggest that mucinous adenocarcinoma is typified by (1) frequent KRAS mutations and a growing list of gene fusions, but rare TP53 mutations, (2) a low mutation burden overall, and (3) a recurrence-free survival similar to stage-matched nonmucinous tumors, with recurrences limited to the lungs. C1 [Shim, Hyo Sup; Mari-Kenudson; Zheng, Zongli; Liebers, Matthew; Ho, Quan Hoang; Onozato, Maristela; Le, Long Phi; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Jackson 1015A, Boston, MA 02114 USA. [Shim, Hyo Sup; Cha, Yoon Jin] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea. [Heist, Rebecca S.] Massachusetts Gen Hosp, Ctr Canc, Dept Thorac Oncol, Boston, MA 02114 USA. RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Jackson 1015A, Boston, MA 02114 USA. EM aiafrate@partners.org RI Zheng, Zongli/B-2917-2011 OI Zheng, Zongli/0000-0003-4849-4903 FU Yonsei University College of Medicine [6-2012-0043, 6-2013-0016]; NIH [R21CA161590]; Lungevity Foundation; Upstage Lung Cancer FX This study was supported by a faculty research grant of Yonsei University College of Medicine for 2012 and 2013 (6-2012-0043; 6-2013-0016) to HSS, by NIH grant (R21CA161590) to AJI, and by Lungevity Foundation and Upstage Lung Cancer to RSH. NR 27 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2015 VL 10 IS 8 BP 1156 EP 1162 DI 10.1097/JTO.0000000000000579 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DD1UJ UT WOS:000369707100021 PM 26200269 ER PT J AU Hai, J Sakashita, S Allo, G Ludkovski, O Ng, C Shepherd, FA Tsao, MS AF Hai, Josephine Sakashita, Shingo Allo, Ghassan Ludkovski, Olga Ng, Christine Shepherd, Frances A. Tsao, Ming-Sound TI Inhibiting MDM2-p53 Interaction Suppresses Tumor Growth in Patient-Derived Non-Small Cell Lung Cancer Xenograft Models SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE MDM2 inhibitor; p53; RG7388; Non-small cell lung cancer; Patient-derived xenografts ID ANTAGONIST RG7112; IN-VITRO; P53; CHEMOTHERAPY; MECHANISM AB Background: The tumor suppressor p53 is frequently inactivated in non-small cell lung cancer (NSCLC). Activation of the p53 pathway by inhibition of its negative regulator MDM2 may offer an attractive approach for NSCLC therapy. We evaluated the antitumor activity of the small-molecule MDM2 inhibitor RG7388 in patient-derived xenograft (PDX) models of NSCLC. Methods: We investigated the effect of RG7388 treatment on cell proliferation, cell cycle arrest, and apoptosis using a panel of human NSCLC cell lines (A549, H157, H1650, H1395, and H358) and PDX cell lines (human lung cell lines 12, 137, 277, and 196). PDX-bearing mice were used to test the therapeutic efficacy and pharmacodynamic effects of RG7388 treatment. Results: We demonstrated that RG7388 promotes low nanomolar antiproliferative activity selectively in cell lines with wild-type p53 and p53 pathway activation, resulting in cell cycle arrest and apoptosis. In PDX models, oral administration of RG7388 led to potent dose-dependent and time-dependent activation of p53 and had a significant impact on p53 downstream targets. Daily treatment of RG7388 in mice at 50 and 80 mg/kg/day inhibited tumor growth in three wild-type p53 PDX models. Activation of the p53 pathway inhibited cell proliferation as observed by reduced Ki-67-positive cells in xenograft tumors. However, induction of apoptotic caspase activity was not observed in these tumors. Notably, RG7388 treatment remains effective in tumors lacking MDM2 amplification but expressing wild-type p53. Conclusions: MDM2 small-molecule inhibitor is effective in treating NSCLC tumors with wild-type p53, supporting further clinical investigation as a potential NSCLC therapy. C1 [Hai, Josephine; Sakashita, Shingo; Allo, Ghassan; Ludkovski, Olga; Ng, Christine; Shepherd, Frances A.; Tsao, Ming-Sound] Univ Hlth Network, Princess Margaret Canc Ctr, Room 14-301,101 Coll St, Toronto, ON M5G 1L7, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Hai, Josephine] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Tsao, MS (reprint author), Univ Hlth Network, Princess Margaret Canc Ctr, Room 14-301,101 Coll St, Toronto, ON M5G 1L7, Canada. EM Ming.Tsao@uhn.on.ca FU Canadian Cancer Society Research Institute [020527]; Ontario Ministry of Health and Long Term Care; Princess Margaret Cancer Foundation FX This study was supported by the Canadian Cancer Society Research Institute grant #020527, the Ontario Ministry of Health and Long Term Care, and the Princess Margaret Cancer Foundation. NR 31 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2015 VL 10 IS 8 BP 1172 EP 1180 DI 10.1097/JTO.0000000000000584 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DD1UJ UT WOS:000369707100023 PM 26200271 ER PT J AU Wang, P Schuetz, C Vallabhajosyula, P Medarova, Z Tena, A Wei, LL Yamada, K Deng, SP Markmann, JF Sachs, DH Moore, A AF Wang, Ping Schuetz, Christian Vallabhajosyula, Prashanth Medarova, Zdravka Tena, Aseda Wei, Lingling Yamada, Kazuhiko Deng, Shaoping Markmann, James F. Sachs, David H. Moore, Anna TI Monitoring of Allogeneic Islet Grafts in Nonhuman Primates Using MRI SO TRANSPLANTATION LA English DT Article ID TRANSPLANTED PANCREATIC-ISLETS; IN-VIVO; CELLULAR THERAPEUTICS; IMMUNE REJECTION; BETA-CELLS; IMMUNOPROTECTION; PROLIFERATION; VISUALIZATION; NANOPARTICLES; TRIGGER AB Background. Information regarding the longevity of transplanted pancreatic islet grafts could provide valuable information for treatment options. In our previous studies, we showed that isolated autologous pancreatic islets could be labeled with iron oxide nanoparticles and monitored after transplantation using MRI. Here, we report on in vivo monitoring of a secondary damage that occurs at the later stages because of allogeneic immune rejection. Methods. In the proof-of-principle studies, iron oxidelabeled autologous pancreatic islets were transplanted under the renal capsules of nonhuman primates. To demonstrate acute graft loss, the animals were injected with streptozotocin. Graft monitoring was performed by in vivo MRI. Next, iron oxidelabeled allogeneic islets were transplanted into the liver and monitored by MRI after withdrawal of immunosuppression. Results. In autologous model, we observed a pronounced drop in graft volume after streptozotocin challenge as assessed by MRI. In allogeneic model of islet transplantation, there was an initial islet loss after the procedure followed by relative stabilization of the graft volume. After immunosuppression was discontinued, there was a noticeable drop in graft volume that gradually continued during the course of the study. Importantly, the loss of graft volume observed on MR preceded the raise in blood glucose. Conclusions. This study demonstrated that in vivo MRI was able to reveal graft volume loss before any changes in blood glucose that can be measured by standard methods. We believe that these results could provide means for clinicians to follow islet fate non-invasively and longitudinally using clinically relevant scanners. C1 [Wang, Ping; Medarova, Zdravka; Moore, Anna] Harvard Univ, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Mol Imaging Lab,Med Sch, Bldg 75,13th St, Charlestown, MA 02129 USA. [Schuetz, Christian; Deng, Shaoping; Markmann, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplantat,Dept Surg, Boston, MA USA. [Schuetz, Christian] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Vallabhajosyula, Prashanth; Tena, Aseda; Wei, Lingling; Yamada, Kazuhiko; Sachs, David H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. RP Moore, A (reprint author), Harvard Univ, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Mol Imaging Lab,Med Sch, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu RI Schuetz, Christian/K-5234-2013; OI Schuetz, Christian/0000-0002-6828-4543; Wang, Ping/0000-0001-6712-8939 FU NIAID NIH HHS [U01AI074634, 5R01AI086134-05, 5U19AI102405-02, R01 AI057851, R01 AI086134, U19 AI102405]; NIDDK NIH HHS [R01 DK078615, R01DK078615] NR 33 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD AUG PY 2015 VL 99 IS 8 BP 1574 EP 1581 DI 10.1097/TP.0000000000000682 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DC2YD UT WOS:000369083800023 PM 25806407 ER PT J AU Madariaga, MLL Shanmugarajah, K Michel, SG Villani, V La Muraglia, GM Torabi, R Leonard, DA Randolph, MA Colvin, RB Yamada, K Madsen, JC Cetrulo, CL Sachs, DH AF Madariaga, Maria Lucia L. Shanmugarajah, Kumaran Michel, Sebastian G. Villani, Vincenzo La Muraglia, Glenn M. Torabi, Radbeh Leonard, David A. Randolph, Mark A. Colvin, Robert B. Yamada, Kazuhiko Madsen, Joren C. Cetrulo, Curtis L., Jr. Sachs, David H. TI Immunomodulatory Strategies Directed Toward Tolerance of Vascularized Composite Allografts SO TRANSPLANTATION LA English DT Article ID MISMATCHED RENAL-TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY COMPLEX; LARGE ANIMAL-MODEL; MINIATURE SWINE; CLASS-I; MAINTENANCE IMMUNOSUPPRESSION; TISSUE ALLOTRANSPLANTATION; FACIAL TRANSPLANTATION; PERIPHERAL TOLERANCE; IMMUNE-MECHANISMS AB Background. Achieving tolerance of vascularized composite allografts (VCAs) would improve the risk-to-benefit ratio in patients who undergo this life-enhancing, though not lifesaving, transplant. Kidney cotransplantation along with a short course of high-dose immunosuppression enables tolerance of heart allografts across a full major histocompatibility complex (MHC) mismatch. In this study, we investigated whether tolerance of VCAs across full MHC disparities could be achieved in animals already tolerant of heart and kidney allografts. Methods. Miniature swine that were tolerant of heart and/or kidney allografts long term underwent transplantation of myocutaneous VCA across the same MHC barrier. Before VCA transplant, group 1 (n = 3) underwent class I-mismatched kidney transplantation; group 2 (n = 3) underwent 2 sequential class I-mismatched kidney transplantations; group 3 (n = 2) underwent haploidentical MHC-mismatched heart/kidney transplantation; and group 4 (n = 2) underwent full MHC-mismatched heart/kidney transplantation. Results. All 3 animals in group 1 and 2 of 3 animals in group 2 showed skin rejection within 85 days; 1 animal in group 2 showed prolonged skin survival longer than 200 days. Animals in groups 3 and 4 showed skin rejection within 30 days and regained in vitro evidence of donor responsiveness. Conclusions. This is the first preclinical study in which hearts, kidneys, and VCAs have been transplanted into the same recipient. Despite VCA rejection, tolerance of heart and kidney allografts was maintained. These results suggest that regulatory tolerance of skin is possible but not generally achieved by the same level of immunomodulation that is capable of inducing tolerance of heart and kidney allografts. Achieving tolerance of skin may require additional immunomodulatory therapies. C1 [Madariaga, Maria Lucia L.; Shanmugarajah, Kumaran; Michel, Sebastian G.; Villani, Vincenzo; La Muraglia, Glenn M.; Torabi, Radbeh; Leonard, David A.; Randolph, Mark A.; Colvin, Robert B.; Yamada, Kazuhiko; Madsen, Joren C.; Cetrulo, Curtis L., Jr.; Sachs, David H.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Shanmugarajah, Kumaran; Leonard, David A.; Randolph, Mark A.; Cetrulo, Curtis L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. RP Sachs, DH (reprint author), Transplantat Biol Res Ctr, Bldg 149,13th St, Charlestown, MA USA. EM David.Sachs@tbrc.mgh.harvard.edu OI Villani, Vincenzo/0000-0002-6078-9766 FU NCRR NIH HHS [C06RR020135-01, C06 RR020135]; NHLBI NIH HHS [F32 HL117540, F32HL117540, P01 HL018646, P01HL18646]; NIAID NIH HHS [R01 AI084657, R01AI84657] NR 46 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 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD AUG PY 2015 VL 99 IS 8 BP 1590 EP 1597 DI 10.1097/TP.0000000000000681 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DC2YD UT WOS:000369083800025 PM 25757218 ER PT J AU Evans, LD Stock, EM Zeber, JE Morissette, SB MacCarthy, AA Sako, EY Lappin, J Lawrence, VA MacCarthy, DJ Copeland, LA AF Evans, Lianna D. Stock, Eileen M. Zeber, John E. Morissette, Sandra B. MacCarthy, Andrea A. Sako, Edward Y. Lappin, Jacqueline Lawrence, Valerie A. MacCarthy, Daniel J. Copeland, Laurel A. TI Posttransplantation Outcomes in Veterans With Serious Mental Illness SO TRANSPLANTATION LA English DT Article ID HEART-TRANSPLANTATION; ORGAN-TRANSPLANTATION; LIVER-TRANSPLANTATION; LUNG-TRANSPLANTATION; ADMINISTRATIVE DATA; CO-MORBIDITY; CANDIDATES; SCHIZOPHRENIA; DEPRESSION; DISORDERS AB Background. Anticipating poor recovery due to impaired self-management and appointment-keeping, clinicians may consider serious mental illness (SMI) a significant concern in organ transplantation. However, little empirical evidence exists regarding posttransplantation outcomes for patients with SMI. Methods. This study analyzed health services data to evaluate posttransplantation 3-year survival by SMI status in a nationwide cohort of patients in the Veterans Health Administration (VHA). Results. A total of 960 recipients of solid organ or bone marrow transplants were identified from Veterans Health Administration administrative data extracts for fiscal years 2006 to 2009. Of these, 164 (17%) had an SMI diagnosis before transplantation (schizophrenia, posttraumatic stress, major depressive, and bipolar disorders); 301 (31%) had some other mental illness diagnosis (such as anxiety, adjustment reactions, or substance abuse); and 495 (52%) had no mental health diagnosis. Twenty-two patients (2%) required retransplantation and 208 patients (22%) died during follow-up. Data on whether these were primary or repeat transplantations were unavailable. Rates of attendance at postoperative outpatient visits and number of months for which immunosuppressive drugs fills were recorded were similar among mental illness groups, as were rates of diagnosed immunological rejection. Three-year mortality was equivalent among mental health groups: no mental health (19%) versus other mental illness (23%) versus SMI (27%;X-2 = 5.11; df= 2; P =.08). In adjusted survival models, no effect of mental health status was observed. Conclusions. Serious mental illness diagnosis does not appear to be associated with adverse transplantation outcomes over the first 3 years; however, a potentially diverging survival curve may portend higher mortality at 5 years. C1 [Evans, Lianna D.; Stock, Eileen M.; Zeber, John E.; Morissette, Sandra B.; Copeland, Laurel A.] Cent Texas Vet Hlth Care Syst, Dept Vet Affairs, Temple, TX USA. [Evans, Lianna D.; Stock, Eileen M.; Zeber, John E.; Morissette, Sandra B.; Lappin, Jacqueline; Copeland, Laurel A.] Texas A&M Hlth Sci Ctr, Coll Med, Temple, TX USA. [Stock, Eileen M.; Zeber, John E.; Copeland, Laurel A.] Cent Texas Vet Hlth Care Syst, Ctr Appl Hlth Res, Temple, TX USA. [Morissette, Sandra B.] VISN 17 Ctr Excellence Res Returning War Vet, Dept Vet Affairs, Waco, TX USA. [MacCarthy, Andrea A.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Sako, Edward Y.; Lawrence, Valerie A.; MacCarthy, Daniel J.] UT Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Lappin, Jacqueline] Baylor Scott & White Hlth, Temple, TX USA. RP Evans, LD (reprint author), Cent Texas Vet Hlth Care Syst, 4800 Mem Dr Waco, Waco, TX 76711 USA. EM Lianna.Evans@va.gov OI Copeland, Laurel/0000-0002-9478-0209 NR 36 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 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD AUG PY 2015 VL 99 IS 8 BP E57 EP E65 DI 10.1097/TP.0000000000000616 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DC2YD UT WOS:000369083800002 PM 25706275 ER PT J AU Cheung, HC Shen, A Oo, S Tilahun, H Cohen, MJ Berkowitz, SA AF Cheung, Hong Chen Shen, Aileen Oo, Sarah Tilahun, Hailu Cohen, Marya J. Berkowitz, Seth A. TI Food Insecurity and Body Mass Index: A Longitudinal Mixed Methods Study, Chelsea, Massachusetts, 2009-2013 SO PREVENTING CHRONIC DISEASE LA English DT Article ID US ADULTS; OBESITY; HEALTH; WOMEN; DISPARITIES; EDUCATION; STATES AB Introduction Cross-sectional studies show an association between food insecurity and higher body mass index (BMI), but this finding has not been evaluated longitudinally. Patient perspectives on food choice in resource-constrained environments are not well understood. The objective of this study was to evaluate the longitudinal association between food insecurity and BMI. Methods This mixed methods study used both a retrospective matched cohort and focus groups. For the quantitative analysis, all patients in a community health center who reported food insecurity from October 2009 through March 2010 (n = 457) were followed through August 2013 and compared with controls matched by age, sex, and race/ethnicity (n = 1,974). We evaluated the association between food insecurity and change in BMI by using linear, mixed effects longitudinal models. The qualitative analysis included patients with food insecurity, stratified by BMI. Qualitative data were analyzed by using open coding and grounded theory. Results The mean age of participants was 51 years; 61% were women, and 73% were Hispanic. Baseline BMI was similar in food insecure participants and matched controls. After adjustment in longitudinal analyses, food insecurity was associated with greater increase in BMI (0.15 kg/m(2) per year more than controls, P <.001). Themes identified in 4 focus groups included attitudes and knowledge about food, food access, and food practices. Participants with BMI of 30 kg/m(2) or less highlighted skills such as budgeting and portion control. Conclusion Food insecurity is associated with increase in BMI. The skills of food insecure participants who were not obese, such as portion control and budgeting, may be useful in weight management interventions for vulnerable patients. C1 [Cheung, Hong Chen] Chelsea Hlth Care Ctr, Adult Med, 151 Everett Ave, Chelsea, MA 02150 USA. [Shen, Aileen] Boston Publ Hlth Commiss, Injury Prevent, Boston, MA USA. [Oo, Sarah] Massachusetts Gen Hosp, Dept Community Hlth, Boston, MA 02114 USA. [Tilahun, Hailu] Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA USA. [Cohen, Marya J.] Massachusetts Gen Hosp, Adult Med, Chelsea Hlth Care Ctr, Chelsea, MA USA. [Cheung, Hong Chen; Cohen, Marya J.; Berkowitz, Seth A.] Harvard Univ, Sch Med, Boston, MA USA. [Cohen, Marya J.; Berkowitz, Seth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Cheung, HC (reprint author), Chelsea Hlth Care Ctr, Adult Med, 151 Everett Ave, Chelsea, MA 02150 USA. EM Chencheung.hong@mgh.harvard.edu OI Berkowitz, Seth/0000-0003-1030-4297 NR 29 TC 2 Z9 2 U1 3 U2 3 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD AUG PY 2015 VL 12 AR E125 DI 10.5888/pcd12.150001 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DB6ZQ UT WOS:000368664600003 PM 26247425 ER PT J AU Goins, RT Schure, MB Noonan, C Buchwald, D AF Goins, R. Turner Schure, Marc B. Noonan, Carolyn Buchwald, Dedra TI Prostate Cancer Screening Among American Indians and Alaska Natives: The Health and Retirement Survey, 1996-2008 SO PREVENTING CHRONIC DISEASE LA English DT Article ID US; DISPARITIES; RECOMMENDATION; SURVEILLANCE; BEHAVIORS; URBAN; MEN AB Introduction Among US men, prostate cancer is the leading malignancy diagnosed and the second leading cause of cancer death. Disparities in cancer screening rates exist between American Indians/Alaska Natives and other racial/ethnic groups. Our study objectives were to examine prostate screening at 5 time points over a 12-year period among American Indian/Alaska Native men aged 50 to 75 years, and to compare their screening rates to African American men and white men in the same age group. Methods We analyzed Health and Retirement Study data for 1996, 1998, 2000, 2004, and 2008. Prostate screening was measured by self-report of receipt of a prostate examination within the previous 2 years. Age-adjusted prevalence was estimated for each year. We used regression with generalized estimating equations to compare prostate screening prevalence by year and race. Results Our analytic sample included 119 American Indian/Alaska Native men (n = 333 observations), 1,359 African American men (n = 3,704 observations), and 8,226 white men (n = 24,292 observations). From 1996 to 2008, prostate screening rates changed for each group: from 57.0% to 55.7% among American Indians/Alaska Natives, from 62.0% to 71.2% among African Americans, and from 68.6% to 71.3% among whites. Although the disparity between whites and African Americans shrank over time, it was virtually unchanged between whites and American Indians/Alaska Natives. Conclusion As of 2008, American Indians/Alaska Natives were less likely than African Americans and whites to report a prostate examination within the previous 2 years. Prevalence trends indicated a modest increase in prostate cancer screening among African Americans and whites, while rates remained substantially lower for American Indians/Alaska Natives. C1 [Goins, R. Turner] Western Carolina Univ, Dept Social Work, Coll Hlth & Human Sci, 4121 Little Savannah Rd, Cullowhee, NC 28723 USA. [Schure, Marc B.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Noonan, Carolyn; Buchwald, Dedra] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Goins, RT (reprint author), Western Carolina Univ, Dept Social Work, Coll Hlth & Human Sci, 4121 Little Savannah Rd, Cullowhee, NC 28723 USA. EM rtgoins@wcu.edu FU National Cancer Institute [P50 CA148110] FX This work was supported by grant no. P50 CA148110 from the National Cancer Institute. NR 32 TC 2 Z9 2 U1 0 U2 1 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD AUG PY 2015 VL 12 AR E123 DI 10.5888/pcd12.150088 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DB6ZQ UT WOS:000368664600001 PM 26247423 ER PT J AU Baker, JF Tan, YK Conaghan, PG AF Baker, Joshua F. Tan, York Kiat Conaghan, Philip G. TI Monitoring in established RA: Role of imaging and soluble biomarkers SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Article DE Rheumatoid arthritis; Magnetic resonance imaging; Ultrasound; Soluble biomarkers ID EARLY RHEUMATOID-ARTHRITIS; LOW DISEASE-ACTIVITY; MRI SCORING SYSTEM; DOPPLER ULTRASONOGRAPHIC ASSESSMENT; RADIOGRAPHIC JOINT DAMAGE; ULTRASOUND TASK-FORCE; TREAT-TO-TARGET; CLINICAL REMISSION; BONE EROSIONS; MUSCULOSKELETAL ULTRASOUND AB Rheumatoid arthritis (RA) disease activity often remains difficult to define and to quantify. As a result, numerous techniques to estimate clinical activity have been developed and are in clinical use. Therefore, more objective biomarkers for early detection and accurate measurement and quantification of the disease burden are desired for clinical use and investigative studies. Several imaging and soluble biomarkers have been studied in the disease including conventional radiography, ultrasound, magnetic resonance imaging (MRI), and serum biomarker assays. While these tools are available to physicians in many settings, their role in routine clinical care remains unclear. The goals of this review are to outline the current state of the literature regarding each of these objective tools, assess their strengths and weaknesses, and clarify the knowledge gaps to be filled before these techniques may be more widely used. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Baker, Joshua F.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Div Rheumatol,Perelman Sch Med, Philadelphia, PA 19104 USA. [Baker, Joshua F.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Tan, York Kiat] Singapore Gen Hosp, Dept Rheumatol & Immunol, Singapore, Singapore. [Tan, York Kiat] Duke NUS Grad Med Sch, Singapore, Singapore. [Tan, York Kiat] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore. [Conaghan, Philip G.] Univ Leeds, Leeds Inst Rheumat & Musculoskeletal Med, Leeds LS7 4SA, W Yorkshire, England. [Conaghan, Philip G.] Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. RP Conaghan, PG (reprint author), Univ Leeds, Chapel Allerton Hosp, Leeds Inst Rheumat & Musculoskeletal Med, Leeds LS7 4SA, W Yorkshire, England. EM bakerjo@uphs.upenn.edu; tan.york.kiat@singhealth.com.sg; p.conaghan@leeds.ac.uk FU Veterans Affairs Clinical Science Research and Development Career Development Award [IK2 CX000955]; Arthritis Research, UK FX Dr. Baker is supported by a Veterans Affairs Clinical Science Research and Development Career Development Award (IK2 CX000955). The contents of this work do not represent the views of the Department of the Veterans Affairs or the United States Government. Professor Conaghan is supported in part by a grant from Arthritis Research, UK. NR 97 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6942 EI 1521-1770 J9 BEST PRACT RES CL RH JI Best Pract. Res. Clin. Rheumatol. PD AUG-DEC PY 2015 VL 29 IS 4-5 BP 566 EP 579 DI 10.1016/j.berh.2015.09.002 PG 14 WC Rheumatology SC Rheumatology GA DA4IE UT WOS:000367762800005 PM 26697767 ER PT J AU Rojas, JM Matsen, ME Mundinger, TO Morton, GJ Stefanovski, D Bergman, RN Kaiyala, KJ Taborsky, GJ Schwartz, MW AF Rojas, Jennifer M. Matsen, Miles E. Mundinger, Thomas O. Morton, Gregory J. Stefanovski, Darko Bergman, Richard N. Kaiyala, Karl J. Taborsky, Gerald J., Jr. Schwartz, Michael W. TI Glucose intolerance induced by blockade of central FGF receptors is linked to an acute stress response SO MOLECULAR METABOLISM LA English DT Article DE Central FGF receptors; FGF receptor inhibitor PD173074; Frequently sampled intravenous glucose tolerance test; Sympathoadrenal response; Minimal model; Glucose metabolism ID GROWTH-FACTOR; FOOD-INTAKE; INSULIN SENSITIVITY; INDIVIDUAL TISSUES; ENERGY-EXPENDITURE; RATS; TOLERANCE; METABOLISM; CATECHOLAMINES; EPINEPHRINE AB Objective: Central administration of ligands for fibroblast growth factor receptors (FGFRs) such as fibroblast growth factor-19 (FGF19) and FGF21 exert glucose-lowering effects in rodent models of obesity and type 2 diabetes (T2D). Conversely, intracerebroventricular (icv) administration of the non-selective FGFR inhibitor (FGFRi) PD173074 causes glucose intolerance, implying a physiological role for neuronal FGFR signaling in glucose homeostasis. The current studies were undertaken to identify neuroendocrine mechanisms underlying the glucose intolerance induced by pharmacological blockade of central FGFRs. Methods: Overnight fasted, lean, male, Long-Evans rats received icv injections of either PD173074 or vehicle (Veh) followed 30 min later by performance of a frequently sampled intravenous glucose tolerance test (FSIGT). Minimal model analysis of glucose and insulin data from the FSIGT was performed to estimate insulin-dependent and insulin-independent components of glucose disposal. Plasma levels of lactate, glucagon, corticosterone, non-esterified free fatty acids (NEFA) and catecholamines were measured before and after intravenous (iv) glucose injection. Results: Within 20 min of icv PD173074 injection (prior to the FSIGT), plasma levels of lactate, norepinephrine and epinephrine increased markedly, and each returned to baseline rapidly (within 8 min) following the iv glucose bolus. In contrast, plasma glucagon levels were not altered by icv FGFRi at either time point. Consistent with a previous report, glucose tolerance was impaired following icv PD173074 compared to Veh injection and, based on minimal model analysis of FSIGT data, this effect was attributable to reductions of both insulin secretion and the basal insulin effect (BIE), consistent with the inhibitory effect of catecholamines on pancreatic beta-cell secretion. By comparison, there were no changes in glucose effectiveness at zero insulin (GEZI) or the insulin sensitivity index (SI). To determine if iv glucose (given during the FSIGT) contributed to the rapid resolution of the sympathoadrenal response induced by icv FGFRi, we performed an additional study comparing groups that received iv saline or iv glucose 30 min after icv FGFRi. Our finding that elevated plasma catecholamine levels returned rapidly to baseline irrespective of whether rats subsequently received an iv bolus of saline or glucose indicates that the rapid reversal of sympathoadrenal activation following icv FGFRi was unrelated to the subsequent glucose bolus. Conclusions: The effect of acute inhibition of central FGFR signaling to impair glucose tolerance likely involves a stress response associated with pronounced, but transient, sympathoadrenal activation and an associated reduction of insulin secretion. Whether this effect is a true consequence of FGFR blockade or involves an off-target effect of the FGFR inhibitor requires additional study. (C) 2015 The Authors. Published by Elsevier GmbH. C1 [Rojas, Jennifer M.; Matsen, Miles E.; Mundinger, Thomas O.; Morton, Gregory J.; Taborsky, Gerald J., Jr.; Schwartz, Michael W.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Taborsky, Gerald J., Jr.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Stefanovski, Darko] Univ Penn, Sch Vet Med, New Bolton Ctr, Philadelphia, PA 19104 USA. [Bergman, Richard N.] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA. [Kaiyala, Karl J.] Univ Washington, Sch Dent, Dept Dent Publ Hlth Sci, Seattle, WA 98195 USA. RP Schwartz, MW (reprint author), Univ Washington, Dept Med, South Lake Union, 850 Republican St,N334,Box 358055, Seattle, WA 98195 USA. EM mschwart@u.washington.edu FU NIDDK NIH HHS [R01 DK089056, T32 DK007247, P30 DK017047, R01 DK029867, R37 DK027619, R01 DK083042, P30 DK035816, R01 DK101997, R01 DK027619, R01 DK090320] NR 35 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2212-8778 J9 MOL METAB JI Mol. Metab. PD AUG PY 2015 VL 4 IS 8 BP 561 EP 568 DI 10.1016/j.molmet.2015.05.005 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CZ9VR UT WOS:000367445600002 PM 26266088 ER PT J AU Bauer, DE Orkin, SH AF Bauer, Daniel E. Orkin, Stuart H. TI Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID REGULATES HEMATOPOIETIC STEM; GENOME-WIDE ASSOCIATION; SICKLE-CELL-DISEASE; ZINC-FINGER PROTEIN; GLOBIN GENE; BETA-GLOBIN; MICRODELETION SYNDROME; LYMPHOID DEVELOPMENT; HUMAN ERYTHROBLASTS; ERYTHROID-CELLS AB The major disorders of beta-globin, sickle cell disease and beta-thalassemia, may be ameliorated by expression of the fetal gene paralog gamma-globin. Uncertainty regarding the mechanisms repressing fetal hemoglobin in the adult stage has served as a puzzle of developmental gene regulation as well as a barrier to rational therapeutic design. Recent genome-wide association studies implicated the zinc-finger transcriptional repressor BCL11A in fetal hemoglobin regulation. Extensive genetic analyses have validated BCL11A as a potent repressor of fetal hemoglobin level. Studies of BCL11A exemplify how contextual gene regulation may often be the substrate for trait-associated common genetic variation. These discoveries have suggested novel rational approaches for the beta-hemoglobin disorders including therapeutic genome editing. C1 [Bauer, Daniel E.; Orkin, Stuart H.] Boston Childrens Hosp, Boston, MA 02115 USA. [Bauer, Daniel E.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bauer, Daniel E.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bauer, Daniel E.; Orkin, Stuart H.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Bauer, DE (reprint author), Boston Childrens Hosp, Boston, MA 02115 USA. EM daniel.bauer@childrens.harvard.edu; stuart_orkin@dfci.harvard.edu FU NIH [DK093705, HL32259, HL032262, DK49216, HL117720]; Doris Duke Charitable Foundation FX Thanks to Diane Chen and Jill Desimini for assistance with figure preparation and to Victoria Hargreaves for critical review. Related work from our laboratories is funded by the NIH (DK093705 to D.E.B. and HL32259, HL032262, DK49216, and HL117720 to S.H.O.) and Doris Duke Charitable Foundation. S.H.O. is an Investigator of the Howard Hughes Medical Institute. NR 73 TC 18 Z9 18 U1 3 U2 12 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X EI 1879-0380 J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD AUG PY 2015 VL 33 BP 62 EP 70 DI 10.1016/j.gde.2015.08.001 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA CZ1XI UT WOS:000366898800009 PM 26375765 ER PT J AU Secemsky, EA Scherzer, R Nitta, E Wu, AHB Lange, DC Deeks, SG Martin, JN Snider, J Ganz, P Hsue, PY AF Secemsky, Eric A. Scherzer, Rebecca Nitta, Elaine Wu, Alan H. B. Lange, David C. Deeks, Steven G. Martin, Jeffrey N. Snider, James Ganz, Peter Hsue, Priscilla Y. TI Novel Biomarkers of Cardiac Stress, Cardiovascular Dysfunction, and Outcomes in HIV-Infected Individuals SO JACC-HEART FAILURE LA English DT Article DE biomarkers; cardiovascular dysfunction; death; HIV; mortality ID GROWTH-DIFFERENTIATION FACTOR-15; HUMAN-IMMUNODEFICIENCY-VIRUS; PULMONARY ARTERIAL-HYPERTENSION; ACUTE CORONARY SYNDROME; CHRONIC HEART-FAILURE; PROGNOSTIC UTILITY; DIASTOLIC FUNCTION; DISEASE; RISK; ECHOCARDIOGRAPHY AB OBJECTIVES This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality. BACKGROUND HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information. METHODS Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age-and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction <50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure >= 35 mm Hg. Mortality data were obtained from the National Death Index. RESULTS Patients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy. CONCLUSIONS Among HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death. (C) 2015 by the American College of Cardiology Foundation. C1 [Secemsky, Eric A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Scherzer, Rebecca] Univ Calif San Francisco, Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94143 USA. [Nitta, Elaine; Ganz, Peter; Hsue, Priscilla Y.] Univ Calif San Francisco, Div Cardiol, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA. [Wu, Alan H. B.] Univ Calif San Francisco, Lab Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Lange, David C.] Cedars Sinai Med Ctr, Dept Med, Div Cardiol, Los Angeles, CA USA. [Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94143 USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Martin, Jeffrey N.] San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94110 USA. [Snider, James] Crit Diagnost, San Diego, CA USA. RP Hsue, PY (reprint author), Univ Calif San Francisco, Div Cardiol, San Francisco Gen Hosp, 1001 Potrero Ave,SFGH 5G20,Box 0846, San Francisco, CA 94143 USA. EM phsue@medsfgh.ucsf.edu FU Merck; National Heart, Lung, and Blood Institute [RO1 HL095130, RO1 HL091526] FX Dr. Scherzer has received honorarium from Merck for participating in an HIV Renal Expert Input Forum; the honorarium was donated to the Northern California Institute for Research and Education to support kidney research. Dr. Wu has a patent with and receives speaker fees from Singulex. Dr. Hsue has received honoraria from Gilead and Pfizer; and grant support from the National Heart, Lung, and Blood Institute (RO1 HL095130 and RO1 HL091526). Dr. Snider is an employee of Critical Care Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 28 TC 8 Z9 8 U1 1 U2 3 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 AUG PY 2015 VL 3 IS 8 BP 591 EP 599 DI 10.1016/j.jchf.2015.03.007 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4FM UT WOS:000365654400002 PM 26164679 ER PT J AU Januzzi, JL Mann, DL AF Januzzi, James L. Mann, Douglas L. TI Light Chains and the Failing Heart Important Mechanistic Link or Fifty Shades of Gray? SO JACC-HEART FAILURE LA English DT Editorial Material DE biomarker; heart failure; inflammation; prognosis ID FAILURE; BIOMARKERS; THERAPY C1 [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Mann, Douglas L.] Washington Univ, Sch Med, Div Cardiol, St Louis, MO USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 10 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 2015 VL 3 IS 8 BP 626 EP 628 DI 10.1016/j.jchf.2015.03.012 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4FM UT WOS:000365654400007 PM 26251089 ER PT J AU Vodovar, N Seronde, MF Laribi, S Gayat, E Lassus, J Januzzi, JL Boukef, R Nouira, S Manivet, P Samuel, JL Logeart, D Cohen-Solal, A Richards, AM Launay, JM Mebazaa, A AF Vodovar, Nicolas Seronde, Marie-France Laribi, Said Gayat, Etienne Lassus, Johan Januzzi, James L., Jr. Boukef, Riadh Nouira, Semir Manivet, Philippe Samuel, Jane-Lise Logeart, Damien Cohen-Solal, Alain Richards, A. Mark Launay, Jean-Marie Mebazaa, Alexandre CA GREAT Network TI Elevated Plasma B-Type Natriuretic Peptide Concentrations Directly Inhibit Circulating Neprilysin Activity in Heart Failure SO JACC-HEART FAILURE LA English DT Article DE BNP; BNP-mediated neprilysin inhibition; heart failure; neprilysin; substance P ID NEUTRAL ENDOPEPTIDASE; TASK-FORCE; CD-NP; OMAPATRILAT; HYDROLYSIS; GUIDELINES; MANAGEMENT; RESISTANCE; ENALAPRIL; SYSTEM AB OBJECTIVES This study sought to hypothesize that elevated B-type natriuretic peptide (BNP) could act as an endogenous neprilysin inhibitor. BACKGROUND A hallmark of acute decompensated heart failure (ADHF) is the overproduction of natriuretic peptides (NPs) by stretched cardiomyocytes. Various strategies have been developed to potentiate the beneficial effect of the NPs, including the recent use of neprilysin angiotensin receptor inhibitors. Contrary to rodents, human BNP is poorly sensitive to neprilysin degradation while retaining affinity to neprilysin. METHODS We enrolled 638 patients presenting to the emergency department with acute dyspnea of which 468 had ADHF and 169 had dyspnea of noncardiac origin. We also included 46 patients with stable chronic heart failure (HF) and 10 age-matched healthy subjects. Plasma samples were collected within 4 h after emergency department admission. BNP, neprilysin concentration and activity, and the neprilysin substrate substance P concentration were measured. RESULTS We found that when plasma BNP rose above 916 pg/ml, neprilysin activity was markedly reduced (p < 0.0001) and stratified 95% of the population into 2 groups: BNP < 916 pg/ml/neprilysin activity >= 0.21 nmol/ml/min and BNP >= 916 pg/ml/neprilysin activity < 0.21 nmol/ml/min with very different prognoses. In vitro, BNP was responsible for neprilysin inhibition. Neprilysin activity was inversely correlated with the concentration of substance P (rho = -0.80; p < 0.0001). CONCLUSIONS Besides being an effector of the cardiac response to cardiomyocyte stretching in ADHF, elevated plasma BNP is also an endogenous neprilysin inhibitor. A biologically relevant BNP threshold discriminates 2 populations of HF patients with different vasoactive peptide profiles and outcome. If confirmed, this may identify an important threshold for managing HF patients. (C) 2015 by the American College of Cardiology Foundation. C1 [Vodovar, Nicolas; Seronde, Marie-France; Laribi, Said; Gayat, Etienne; Manivet, Philippe; Samuel, Jane-Lise; Logeart, Damien; Cohen-Solal, Alain; Launay, Jean-Marie; Mebazaa, Alexandre] INSERM, UMR S 942, Paris, France. [Vodovar, Nicolas; Manivet, Philippe; Samuel, Jane-Lise; Logeart, Damien; Cohen-Solal, Alain; Launay, Jean-Marie] DHU FIRE, Paris, France. [Seronde, Marie-France] Univ Hosp Jean Minjoz, EA3920, Dept Cardiol, Besancon, France. [Laribi, Said] Lariboisiere Hosp, Dept Emergency Med, Paris, France. [Gayat, Etienne; Mebazaa, Alexandre] DHU Neurovasc, Paris, France. [Gayat, Etienne; Samuel, Jane-Lise; Mebazaa, Alexandre] Lariboisiere Hosp, Dept Anaesthesiol & Intens Care, Paris, France. [Lassus, Johan] Univ Helsinki, Cent Hosp, Div Cardiol, Heart & Lung Ctr, Helsinki, Finland. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Boukef, Riadh; Nouira, Semir] Fattouma Bourguiba Univ Hosp, Emergency Dept, Monastir, Tunisia. [Boukef, Riadh; Nouira, Semir] Fattouma Bourguiba Univ Hosp, Res Unit UR06SP21, Monastir, Tunisia. [Manivet, Philippe; Launay, Jean-Marie] Lariboisiere Hosp, Dept Biochem, Paris, France. [Manivet, Philippe; Launay, Jean-Marie] Lariboisiere Hosp, Ctr Biol Resources BB 0033 00064, Paris, France. [Logeart, Damien; Cohen-Solal, Alain] Lariboisiere Hosp, Dept Cardiol, Paris, France. [Logeart, Damien; Cohen-Solal, Alain; Mebazaa, Alexandre] Paris Diderot Univ, Sorbonne Paris Cite, Paris, France. [Richards, A. Mark] Univ Otago, Christchurch, New Zealand. [Richards, A. Mark] Natl Univ Hlth Syst, Singapore, Singapore. RP Mebazaa, A (reprint author), Lariboisiere Hosp, Dept Anesthesiol & Intens Care, 2 Rue A Pare, F-75475 Paris, France. EM jean-marie.launay@lrb.aphp.fr; alexandre.mebazaa@lrb.aphp.fr RI Laribi, said/S-3693-2016; OI Vodovar, Nicolas/0000-0001-8087-387X; Nouira, Semir/0000-0002-0137-5491; Samuel, Jane-Lise/0000-0002-7346-2404 FU Inserm; Roche; Thermo Fisher; Fondation Coeur et Recherche; National University of Singapore-University Sorbonne Paris Cite (NUS-USPC) Alliance; DHU FIRE; European Commission's Seventh Framework program [305507]; Servier; Bristol-Myers Squibb; Siemens; Singulex; Critical Diagnostics; Sphingotc; Amgen; Novartis; Actelion; Ipsen; Sorin; Abbott; Alere; Pfizer; Vifor; Bayer; Sanofi; Boehringer Ingelheim; Roche Diagnostics FX This work was financed by Inserm and research grants received from Roche, Thermo Fisher, the Fondation Coeur et Recherche, the National University of Singapore-University Sorbonne Paris Cite (NUS-USPC) Alliance, and the DHU FIRE. Dr. Vodovar is supported by a post-doctoral fellowship from the European Commission's Seventh Framework program under grant agreement No. 305507 (HOMAGE). Dr. Gayat has received travel fees from Servier; and has received lecture fees from Bristol-Myers Squibb. Dr. Lassus has received honoraria from Roche Diagnostics, Novartis, Vifor Pharma, Bayer, Orion Pharma, and Pfizer. Dr. Januzzi has received research grants from Siemens, Singulex, and Thermo Fisher; and has received consulting fees from Roche, Critical Diagnostics, Sphingotc, Amgen, and Novartis. Dr. Logeart has received honorarium from Biotronic, Boston Scientific, Cordis, Roche Diagnostics, Novartis, Pfizer, and Servier. Dr. Solal has received speaker and consulting fees from Actelion, Ipsen, Sorin, Abbott, Novartis, Thermo Fisher, Alere, Pfizer, Vifor, Amgen, Servier, Bayer, Sanofi, and Boehringer Ingelheim. Dr. Richards has received research grants, speaker fees, and travel support from Roche Diagnostics and Alere. Dr. Mebazaa has received speaker honoraria from Cardiorentis, The Medicines Company, Critical Diagnostics, Vifor, Orion, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Vodovar and Seronde contributed equally to this work. NR 36 TC 16 Z9 17 U1 0 U2 3 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 AUG PY 2015 VL 3 IS 8 BP 629 EP 636 DI 10.1016/j.jchf.2015.03.011 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4FM UT WOS:000365654400008 PM 26251090 ER PT J AU Spielberg, JM Jarcho, JM Dahl, RE Pine, DS Ernst, M Nelson, EE AF Spielberg, Jeffrey M. Jarcho, Johanna M. Dahl, Ronald E. Pine, Daniel S. Ernst, Monique Nelson, Eric E. TI Anticipation of peer evaluation in anxious adolescents: divergence in neural activation and maturation SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE anxiety; adolescence; anticipation; amygdala; nucleus accumbens ID ANTERIOR CINGULATE CORTEX; HUMAN AMYGDALA; NUCLEUS-ACCUMBENS; ANXIETY; BRAIN; EMOTION; CONNECTIVITY; DEPRESSION; DISORDERS; CHILDHOOD AB Adolescence is the time of peak onset for many anxiety disorders, particularly Social Anxiety Disorder. Research using simulated social interactions consistently finds differential activation in several brain regions in anxious (vs non-anxious) youth, including amygdala, striatum and medial prefrontal cortex. However, few studies examined the anticipation of peer interactions, a key component in the etiology and maintenance of anxiety disorders. Youth completed the Chatroom Task while undergoing functional magnetic resonance imaging. Patterns of neural activation were assessed in anxious and non-anxious youth as they were cued to anticipate social feedback from peers. Anxious participants evidenced greater amygdala activation and rostral anterior cingulate (rACC)<-> amygdala coupling than non-anxious participants during anticipation of feedback from peers they had previously rejected; anxious participants also evidenced less nucleus accumbens activation during anticipation of feedback from selected peers. Finally, anxiety interacted with age in rACC: in anxious participants, age was positively associated with activation to anticipated feedback from rejected peers and negatively for selected peers, whereas the opposite pattern emerged for non-anxious youth. Overall, anxious youth showed greater reactivity in anticipation of feedback from rejected peers and thus may ascribe greater salience to these potential interactions and increase the likelihood of avoidance behavior. C1 [Spielberg, Jeffrey M.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Spielberg, Jeffrey M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Jarcho, Johanna M.; Pine, Daniel S.; Ernst, Monique; Nelson, Eric E.] NIMH, Bethesda, MD 20814 USA. [Dahl, Ronald E.] Univ Calif Berkeley, Inst Human Dev, Berkeley, CA 94720 USA. RP Spielberg, JM (reprint author), VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, 150 South Huntington Ave 182 JP, Boston, MA 02130 USA. EM spielbergjm@gmail.com OI Jarcho, Johanna/0000-0001-9075-6968; Nelson, Eric/0000-0002-3376-2453 FU National Institute of Mental Health FX This study was supported by the intramural research program of the National Institute of Mental Health. NR 51 TC 5 Z9 5 U1 6 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD AUG PY 2015 VL 10 IS 8 BP 1084 EP 1091 DI 10.1093/scan/nsu165 PG 8 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CX2PW UT WOS:000365540100009 PM 25552568 ER PT J AU Hur, J Miller, GA McDavitt, JRB Spielberg, JM Crocker, LD Infantolino, ZP Towers, DN Warren, SL Heller, W AF Hur, Juyoen Miller, Gregory A. McDavitt, Jenika R. B. Spielberg, Jeffrey M. Crocker, Laura D. Infantolino, Zachary P. Towers, David N. Warren, Stacie L. Heller, Wendy TI Interactive effects of trait and state affect on top-down control of attention SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE trait affect; state affect; attention; cognitive control; interference ID DORSOLATERAL PREFRONTAL CORTEX; EXECUTIVE FUNCTION; COGNITIVE-CONTROL; POSITIVE AFFECT; MOOD INDUCTION; EMOTION; DEPRESSION; BRAIN; ANXIETY; FMRI AB Few studies have investigated how attentional control is affected by transient affective states while taking individual differences in affective traits into consideration. In this study, participants completed a color-word Stroop task immediately after undergoing a positive, neutral or negative affective context manipulation (ACM). Behavioral performance was unaffected by any ACM considered in isolation. For individuals high in trait negative affect (NA), performance was impaired by the negative but not the positive or neutral ACM. Neuroimaging results indicate that activity in primarily top-down control regions of the brain (inferior frontal gyrus and dorsal anterior cingulate cortex) was suppressed in the presence of emotional arousal (both negative and positive ACMs). This effect appears to have been exacerbated or offset by co-occurring activity in other top-down control regions (parietal) and emotion processing regions (orbitofrontal cortex, amygdala and nucleus accumbens) as a function of the valence of state affect (positive or negative) and trait affect (trait NA or trait PA). Neuroimaging results are consistent with behavioral findings. In combination, they indicate both additive and interactive influences of trait and state affect on top-down control of attention. C1 [Hur, Juyoen; Miller, Gregory A.; McDavitt, Jenika R. B.; Spielberg, Jeffrey M.; Crocker, Laura D.; Infantolino, Zachary P.; Towers, David N.; Warren, Stacie L.; Heller, Wendy] Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. [Miller, Gregory A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Miller, Gregory A.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Spielberg, Jeffrey M.] Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA 02130 USA. [Infantolino, Zachary P.] Univ Delaware, Dept Psychol, Newark, DE 19716 USA. [Towers, David N.] Univ Illinois, Dept Psychol, Springfield, IL 62703 USA. [Warren, Stacie L.] Palo Alto Univ, Dept Psychol, Palo Alto, CA 94304 USA. RP Heller, W (reprint author), Univ Illinois, Dept Psychol, 603 E Daniel St, Champaign, IL 61821 USA. EM w-heller@illinois.edu OI Warren, Stacie/0000-0002-6096-5950; Spielberg, Jeffrey/0000-0001-8348-7157 FU National Institute of Mental Health [P50 MH079485, R01 MH61358, T32 MH19554] FX This work was supported by the National Institute of Mental Health (P50 MH079485, R01 MH61358, T32 MH19554). The authors thank Katherine Mimnaugh and Marie T. Banich for their contributions to this project. NR 51 TC 3 Z9 3 U1 8 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD AUG PY 2015 VL 10 IS 8 BP 1128 EP 1136 DI 10.1093/scan/nsu163 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CX2PW UT WOS:000365540100014 PM 25556211 ER PT J AU Nieman, LK Biller, BMK Findling, JW Murad, MH Newell-Price, J Savage, MO Tabarin, A AF Nieman, Lynnette K. Biller, Beverly M. K. Findling, James W. Murad, M. Hassan Newell-Price, John Savage, Martin O. Tabarin, Antoine TI Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID QUALITY-OF-LIFE; LONG-TERM REMISSION; MACRONODULAR ADRENAL-HYPERPLASIA; ADRENOCORTICOTROPIC HORMONE SYNDROME; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; DOPAMINE-RECEPTOR EXPRESSION; MEDULLARY-THYROID CARCINOMA; MCCUNE-ALBRIGHT SYNDROME; LOW-DOSE ETOMIDATE; TRANSSPHENOIDAL SURGERY AB Objective: The objective is to formulate clinical practice guidelines for treating Cushing's syndrome. Participants: Participants include an Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. The European Society for Endocrinology co-sponsored the guideline. Evidence: The Task Force used the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: The Task Force achieved consensus through one group meeting, several conference calls, and numerous e-mail communications. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Conclusions: Treatment of Cushing's syndrome is essential to reduce mortality and associated comorbidities. Effective treatment includes the normalization of cortisol levels or action. It also includes the normalization of comorbidities via directly treating the cause of Cushing's syndrome and by adjunctive treatments (eg, antihypertensives). Surgical resection of the causal lesion(s) is generally the first-line approach. The choice of second-line treatments, including medication, bilateral adrenalectomy, and radiation therapy (for corticotrope tumors), must be individualized to each patient. C1 [Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Findling, James W.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Murad, M. Hassan] Mayo Clin, Div Prevent Med, Rochester, MN 55905 USA. [Newell-Price, John] Univ Sheffield, Dept Human Metab, Sch Med & Biomed Sci, Sheffield S10 2RX, S Yorkshire, England. [Savage, Martin O.] Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England. [Tabarin, Antoine] Ctr Hosp Univ Bordeaux, Dept Endocrinol, F-33077 Bordeaux, France. Univ Bordeaux, Inserm 862, F-33077 Bordeaux, France. RP Nieman, LK (reprint author), Endocrine Soc, 2055 L St NW,Suite 600, Washington, DC 20036 USA. EM govt-prof@endocrine.org FU Intramural Research Program of the Eunice Kennedy Shriver Institute of Child Health and Human Development FX The Intramural Research Program of the Eunice Kennedy Shriver Institute of Child Health and Human Development provided salary support to Dr Nieman for her work on this manuscript. NR 212 TC 55 Z9 62 U1 6 U2 11 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2015 VL 100 IS 8 BP 2807 EP 2831 DI 10.1210/jc.2015-1818 PG 25 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW2XH UT WOS:000364855900019 PM 26222757 ER PT J AU Srinivasa, S Fitch, KV Wong, K Torriani, M Mayhew, C Stanley, T Lo, J Adler, GK Grinspoon, SK AF Srinivasa, Suman Fitch, Kathleen V. Wong, Kimberly Torriani, Martin Mayhew, Caitlin Stanley, Takara Lo, Janet Adler, Gail K. Grinspoon, Steven K. TI RAAS Activation Is Associated With Visceral Adiposity and Insulin Resistance Among HIV-infected Patients SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BODY-MASS INDEX; METABOLIC ABNORMALITIES; ALDOSTERONE PRODUCTION; ANGIOTENSIN-II; 3T3-L1 CELLS; TISSUE; OBESITY; FAT; EXPRESSION AB Context: Little is known about renin-angiotensin-aldosterone system (RAAS) activation in relationship to visceral adipose tissue (VAT) accumulation in HIV-infected patients, a population at significant risk for insulin resistance and other metabolic disease. Design: Twenty HIV and 10 non-HIV-infected subjects consumed a standardized low sodium or liberal sodium diet to stimulate or suppress the RAAS, respectively. RAAS parameters were evaluated in response to each diet and a graded angiotensin II infusion. Further analyses were performed after groups were substratified by median VAT measured by magnetic resonance imaging. Results: Aldosterone concentrations during the low-sodium diet were higher in HIV than non-HIV-infected subjects [13.8 (9.7, 30.9) vs 9.2 (7.6, 13.6) ng/dL, P = .03] and increased across groups stratified by visceral adipose tissue (VAT) [8.5 (7.1, 12.8), 9.2 (8.1, 21.5), 11.4 (9.4, 13.8), and 27.2 (13.0, 36.9) ng/dL in non-HIV-infected without increased VAT, non-HIV-infected with increased VAT, HIV-infected without increased VAT, HIV-infected with increased VAT, respectively, overall trend P = .02]. Under this condition, plasma renin activity [3.50 (2.58, 4.65) vs 1.45 (0.58, 2.33) ng/mL . h, P = .002] was higher among the HIV-infected subjects with vs without increased VAT. Differences in the suppressibility of plasma renin activity by graded angiotensin infusion were seen stratifying by VAT among the HIV-infected group (P < .02 at each dose). In addition, aldosterone (P = .007) was an independent predictor of insulin resistance in multivariate modeling, controlling for VAT and adiponectin. Conclusion: These data suggest excess RAAS activation in relationship to visceral adiposity in HIV-infected patients that may independently contribute to insulin resistance. Mineralocorticoid blockade may have therapeutic potential to reduce metabolic complications in HIV-infected patients with increased visceral adiposity. C1 [Srinivasa, Suman; Fitch, Kathleen V.; Wong, Kimberly; Stanley, Takara; Lo, Janet; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Torriani, Martin] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mayhew, Caitlin; Adler, Gail K.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. EM sgrinspoon@mgh.harvard.edu FU National Institutes of Health (NIH) Grant [R01DK49302]; NIH [K24 HL103845, M01RR01066, UL1 RR025758, UL1 TR001102]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases Grant [P30DK40561]; Pilot and Feasibility Grant, Nutrition and Obesity Research Center at Harvard FX This work was supported by National Institutes of Health (NIH) Grant R01DK49302 (to S.K.G.); NIH Grant K24 HL103845 (to G.K.A.); NIH Grants M01RR01066, UL1 RR025758, and UL1 TR001102 (to the Harvard Catalyst/Harvard Clinical and Translational Science Center from the National Center for Research Resources and the National Center for Advancing Translational Sciences); and NIH/National Institute of Diabetes and Digestive and Kidney Diseases Grant P30DK40561, a Pilot and Feasibility Grant, Nutrition and Obesity Research Center at Harvard. NR 38 TC 12 Z9 12 U1 1 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2015 VL 100 IS 8 BP 2873 EP 2882 DI 10.1210/jc.2015-1461 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW2XH UT WOS:000364855900027 PM 26086328 ER PT J AU Yeoh, AJ Pedley, A Rosenquist, KJ Hoffmann, U Fox, CS AF Yeoh, Aaron J. Pedley, Alison Rosenquist, Klara J. Hoffmann, Udo Fox, Caroline S. TI The Association Between Subcutaneous Fat Density and the Propensity to Store Fat Viscerally SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CARDIOMETABOLIC RISK PROFILE; ADIPOSE-TISSUE FIBROSIS; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; HUMAN OBESITY; FRAMINGHAM; HEART; DYSFUNCTION; ACCUMULATION; INFLAMMATION AB Background: Alterations in the cellular characteristics of subcutaneous adipose tissue (SAT) may reduce its ability to expand in times of caloric excess, increasing the propensity to store excess calories viscerally (visceral adipose tissue [VAT]). We hypothesized (1) that increased SAT density, an indirect marker of fat quality, would be associated with an increased VAT/SAT ratio and increased cardiovascular disease (CVD) risk and (2) that these associations would be independent of the absolute volume of SAT. Methods: We investigated the association of SAT density with the VAT/SAT ratio and CVD risk in 3212 participants (48% women, mean age, 50.7 years) from the Framingham Heart Study. Adipose tissue depot density and volume were quantified by computed tomography; traditional CVD risk factors were quantified. Results: Higher SAT density was correlated with a higher VAT/SAT ratio in men (r = 0.17; P < .0001) but not in women (r = 0.04; P >= .05). More adverse levels of CVD risk factors were observed in the high SAT density/high VAT/SAT ratio group than in the referent group (low density/low ratio). For example, women had an increased risk of diabetes (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.6-17.6; P = .0001) and hypertension (OR, 1.6; 95% CI, 1.1-2.4; P = .009). Additional adjustment for SAT volume generally strengthened these associations (diabetes OR, 10.8; 95% CI, 4.1-29.0; hypertension OR, 2.5; 95% CI, 1.7-3.7; all P = .0001). These trends were similar but generally weaker in men. Conclusion: High fat density, an indirect marker of fat quality, is associated with the propensity to store fat viscerally vs subcutaneously and is jointly characterized by an increased burden of CVD risk factors. C1 [Yeoh, Aaron J.; Pedley, Alison; Rosenquist, Klara J.; Fox, Caroline S.] Natl Heart & Lung Blood Inst Framingham Heart Stu, Framingham, MA 01702 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fox, CS (reprint author), Natl Heart & Lung Blood Inst Framingham Heart Stu, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxa@nhlbi.nih.gov FU National Heart, Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine [N01-HC-25195] FX This work was supported by in part using resources and data from the Framingham Heart Study of the National Heart, Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine (Grant N01-HC-25195). NR 43 TC 6 Z9 6 U1 1 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2015 VL 100 IS 8 BP E1056 EP E1064 DI 10.1210/jc.2014-4032 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW2XH UT WOS:000364855900006 PM 26062015 ER PT J AU Richman, JS Andreae, S Safford, MM AF Richman, Joshua S. Andreae, Susan Safford, Monika M. TI Challenges of Prolonged Follow-up and Temporal Imbalance in Pragmatic Trials: Analysis of the ENCOURAGE Trial SO ANNALS OF FAMILY MEDICINE LA English DT Article DE statistical data interpretation; nonlinear models; community-based trials AB PURPOSE Peer support intervention trials are typically conducted in community-based settings and provide generalizable results. The logistic challenges of community-based trials often result in unplanned temporal imbalances in recruitment and follow-up. When imbalances are present, as in the ENCOURAGE trial, appropriate statistical methods must be used to account for these imbalances. We present the design, conduct, and analysis of the ENCOURAGE trial as a case study of a cluster-randomized, community-based, peer-coaching intervention. METHODS Preliminary data analysis included examination of study data for imbalances in participant characteristics at baseline, the presence of both secular and seasonal trends in outcome measures, and imbalances in time from baseline to follow-up. Additional examination suggested the presence of nonlinear trends in the intervention effect. The final analyses adjusted for all identified imbalances with accounting for community clustering by supplementing linear mixed effect models with generalized additive mixed models (GAMM) to examine nonlinear trends. RESULTS Largely due to the location of participants across a considerable geographic area, temporal imbalances were discovered in recruitment, baseline, and follow-up data collection, along with evidence for both secular and seasonal trends in study outcome measures. Using the standard analytical approach, ENCOURAGE appeared to be a null trial. After incorporating adjustment for these temporal imbalances, linear regression analyses still showed no intervention effect. Upon further analyses using GAMM to consider nonlinear intervention trends, we observed intervention effects that were both significant (P < .05) and nonlinear. DISCUSSION In community-based trials, recruitment and follow-up may not occur as planned, and complex temporal imbalance may greatly influence the analysis. Real-world trials should use careful logistic planning and monitoring to avoid temporal imbalance. If imbalance is unavoidable, sophisticated statistical methods may nevertheless extract useful information, although the potential problem of residual confounding due to other unmeasured imbalances must be considered. C1 [Richman, Joshua S.] Birmingham VA Med Ctr, Birmingham, AL USA. [Richman, Joshua S.] Univ Alabama Birmingham, Sch Med, Dept Surg, Birmingham, AL 35294 USA. [Andreae, Susan; Safford, Monika M.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. RP Richman, JS (reprint author), 1720,2nd Ave South,KB428, Birmingham, AL 35294 USA. EM jrichman@uabmc.edu FU American Academy of Family Physicians Foundation; Eli Lilly and Company Foundation FX Funding for this research was provided by the American Academy of Family Physicians Foundation through the Peers for Progress program with support from the Eli Lilly and Company Foundation. NR 6 TC 1 Z9 1 U1 0 U2 1 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 EI 1544-1717 J9 ANN FAM MED JI Ann. Fam. Med. PD AUG 1 PY 2015 VL 13 SU 1 BP S66 EP S72 DI 10.1370/afm.1790 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA CW2PI UT WOS:000364834300009 PM 26304974 ER PT J AU Safford, MM Andreae, S Cherrington, AL Martin, MY Halanych, J Lewis, M Patel, A Johnson, E Clark, D Gamboa, C Richman, JS AF Safford, Monika M. Andreae, Susan Cherrington, Andrea L. Martin, Michelle Y. Halanych, Jewell Lewis, Marquita Patel, Ashruta Johnson, Ethel Clark, Debra Gamboa, Christopher Richman, Joshua S. TI Peer Coaches to Improve Diabetes Outcomes in Rural Alabama: A Cluster Randomized Trial SO ANNALS OF FAMILY MEDICINE LA English DT Article DE Peer health coaching; self-management support; diabetes; primary care ID HEALTH WORKER INTERVENTION; PATIENT ACTIVATION MEASURE; SELF-MANAGEMENT; AFRICAN-AMERICAN; SUPPORT AB PURPOSE It is unclear whether peer coaching is effective in minority populations living with diabetes in hard-to-reach, under-resourced areas such as the rural South. We examined the effect of an innovative peer-coaching intervention plus brief education vs brief education alone on diabetes outcomes. METHODS This was a community-engaged, cluster-randomized, controlled trial with primary care practices and their surrounding communities serving as clusters. The trial enrolled 424 participants, with 360 completing baseline and follow-up data collection (84.9% retention). The primary outcomes were change in glycated hemoglobin (HbA(1c)), systolic blood pressure (BP), low density lipoprotein cholesterol (LDL-C), body mass index (BMI), and quality of life, with diabetes distress and patient activation as secondary outcomes. Peer coaches were trained for 2 days in community settings; the training emphasized motivational interviewing skills, diabetes basics, and goal setting. All participants received a 1-hour diabetes education class and a personalized diabetes report card at baseline. Intervention arm participants were also paired with peer coaches; the protocol called for telephone interactions weekly for the first 8 weeks, then monthly for a total of 10 months. RESULTS Due to real-world constraints, follow-up was protracted, and intervention effects varied over time. The analysis that included the 68% of participants followed up by 15 months showed only a significant increase in patient activation in the intervention group. The analysis that included all participants who eventually completed follow-up revealed that intervention arm participants had significant differences in changes in systolic BP (P = .047), BMI (P = .02), quality of life (P = .003), diabetes distress (P = .004), and patient activation (P = .03), but not in HbA(1c) (P = .14) or LDL-C (P = .97). CONCLUSION Telephone-delivered peer coaching holds promise to improve health for individuals with diabetes living in under-resourced areas. C1 [Safford, Monika M.; Andreae, Susan; Cherrington, Andrea L.; Martin, Michelle Y.; Halanych, Jewell; Lewis, Marquita; Patel, Ashruta; Johnson, Ethel; Clark, Debra; Gamboa, Christopher] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Johnson, Ethel] West Cent Alabama Community Hlth Improvement Leag, Camden, AL USA. [Clark, Debra] Sumter Cty Hlth & Wellness Educ Ctr, Livingston, AL USA. [Richman, Joshua S.] Birmingham VA Med Ctr, Birmingham, AL USA. [Richman, Joshua S.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Richman, Joshua S.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Safford, MM (reprint author), 1717 11th Ave South, Birmingham, AL 35294 USA. EM msafford@uab.edu FU American Academy of Family Physicians Foundation; Eli Lilly and Company Foundation FX Funding for this research was provided by the American Academy of Family Physicians Foundation through the Peers for Progress program with support from the Eli Lilly and Company Foundation. NR 26 TC 6 Z9 6 U1 5 U2 12 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 EI 1544-1717 J9 ANN FAM MED JI Ann. Fam. Med. PD AUG 1 PY 2015 VL 13 SU 1 BP S18 EP S26 DI 10.1370/afm.1798 PG 9 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA CW2PI UT WOS:000364834300003 PM 26304967 ER PT J AU Gonzalez, AN Barmakian, PM Penson, RT AF Gonzalez, A. N. Barmakian, P. M. Penson, R. T. TI VB-111 Antiangiogenic gene therapy SO DRUGS OF THE FUTURE LA English DT Article DE Vascular targeting system; Recurrent glioblastoma; Thyroid cancer; Ovarian cancer; Antiangiogenic; VB-111 ID OVARIAN-CANCER; TUMOR ANGIOGENESIS; BEVACIZUMAB; CHEMOTHERAPY; EXPRESSION; TRIAL; MICE AB Antiangiogenic therapies have become an integral part of the treatment of many different cancers. Following the FDA approval of bevacizumab (Avastin (R)) in several indications, a set of next-generation angiogenesis inhibitors are emerging in clinical development for multiple types of solid tumors. VB-111 is a novel drug that specifically and selectively targets tumor endothelial cells through an adenovirus-5 vector and modified preproendothelin-1 (PPET1, PPE-1) promoter. With phase I/II clinical studies underway in glioblastoma, thyroid cancer and ovarian cancer, VB-111 has the potential to offer a sustained antiangiogenic effect as a gene therapy approach to cancer treatment. However, in ovarian cancer in particular, it will be of paramount importance to understand the efficacy of VB-111 in combination with conventional chemotherapies, especially given the equivocal evidence surrounding the use of bevacizumab in various ovarian cancer subgroups. C1 [Gonzalez, A. N.; Barmakian, P. M.; Penson, R. T.] Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9066, Boston, MA 02114 USA. EM rpenson@partners.org NR 24 TC 0 Z9 0 U1 1 U2 2 PU PROUS SCIENCE, SAU-THOMSON REUTERS PI BARCELONA PA 398 PROVENCA, 08025 BARCELONA, SPAIN SN 0377-8282 EI 2013-0368 J9 DRUG FUTURE JI Drug Future PD AUG PY 2015 VL 40 IS 8 BP 523 EP 528 DI 10.1358/dof.2015.040.08.2339944 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CW5HO UT WOS:000365026500002 ER PT J AU Aleong, RG Mulvahill, MJ Halder, I Carlson, NE Singh, M Bloom, HL Dudley, SC Ellinor, PT Shalaby, A Weiss, R Gutmann, R Sauer, WH Narayanan, K Chugh, SS Saba, S London, B AF Aleong, Ryan G. Mulvahill, Matthew J. Halder, Indrani Carlson, Nichole E. Singh, Madhurmeet Bloom, Heather L. Dudley, Samuel C. Ellinor, Patrick T. Shalaby, Alaa Weiss, Raul Gutmann, Rebecca Sauer, William H. Narayanan, Kumar Chugh, Sumeet S. Saba, Samir London, Barry TI Left Ventricular Dilatation Increases the Risk of Ventricular Arrhythmias in Patients With Reduced Systolic Function SO Journal of the American Heart Association LA English DT Article DE heart failure; ventricular arrhythmias ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ISOLATED RABBIT HEART; MYOCARDIAL-INFARCTION; SUDDEN-DEATH; PROPHYLACTIC USE; HYPERTROPHY; CARDIOMYOPATHY; REGRESSION; REDUCTION; MORTALITY AB Background-Reduced left ventricular (LV) ejection fraction increases the risk of ventricular arrhythmias; however, LV ejection fraction has a low sensitivity to predict ventricular arrhythmias. LV dilatation and mass may be useful to further risk-stratify for ventricular arrhythmias. Methods and Results-Patients from the Genetic Risk of Assessment of Defibrillator Events (GRADE) study (N=930), a study of heart failure subjects with defibrillators, were assessed for appropriate implantable cardioverter-defibrillator shock and death, heart transplant, or ventricular assist device placement by LV diameter and mass. LV mass was divided into normal, mild, moderate, and severe classifications. Severe LV end-diastolic diameter had worse shock-free survival than normal and mild LV enddiastolic diameter (P=0.0002 and 0.0063, respectively; 2-year shock free, severe 74%, moderate 80%, mild 91%, normal 88%; 4-year shock free, severe 62%, moderate 69%, mild 72%, normal 81%) and freedom from death, transplant, or ventricular assist device compared with normal and moderate LV end-diastolic diameter (P<0.0001 and 0.0441, respectively; 2-year survival: severe 78%, moderate 85%, mild 82%, normal 89%; 4-year survival: severe 55%, moderate 64%, mild 63%, normal 74%). Severe LV mass had worse shock-free survival than normal and mild LV mass (P=0.0370 and 0.0280, respectively; 2-year shock free: severe 80%, moderate 81%, mild 91%, normal 87%; 4-year shock free: severe 68%, moderate 73%, mild 76%, normal 76%) but no association with death, transplant, or ventricular assist device (P=0.1319). In a multivariable Cox proportional hazards analysis adjusted for LV ejection fraction, LV end-diastolic diameter was associated with appropriate implantable cardioverter-defibrillator shocks (hazard ratio 1.22, P=0.020). LV end-diastolic diameter was associated with time to death, transplant, or ventricular assist device (hazard ratio 1.29, P=0.0009). Conclusions-LV dilatation may complement ejection fraction to predict ventricular arrhythmias. C1 [Aleong, Ryan G.; Mulvahill, Matthew J.; Carlson, Nichole E.; Sauer, William H.] Univ Colorado, Denver, CO 80202 USA. [Halder, Indrani; Singh, Madhurmeet; Shalaby, Alaa; Saba, Samir] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Bloom, Heather L.] Emory Univ, Atlanta, GA 30322 USA. [Bloom, Heather L.] Atlanta VA Med Ctr, Atlanta, GA USA. [Dudley, Samuel C.] Brown Univ, Lifespan Cardiovasc Inst, Providence, RI 02912 USA. [Dudley, Samuel C.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shalaby, Alaa] Pittsburgh VA Healthcare Syst, Pittsburgh, PA USA. [Weiss, Raul] Ohio State Univ, Columbus, OH 43210 USA. [Gutmann, Rebecca; London, Barry] Univ Iowa, Iowa City, IA USA. [Narayanan, Kumar; Chugh, Sumeet S.] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. RP Aleong, RG (reprint author), Univ Colorado Hosp, Sect Cardiac Electrophysiol, 12401 E 17th Ave,B136, Aurora, CO 80045 USA. EM ryan.aleong@ucdenver.edu FU National Institutes of Health (NIH)-National Heart, Lung, and Blood Institute (NHLBI) [R01 HL77398]; NIH-NHLBI [R01 HL103946]; NIH-NCATS [UL1 TR001082] FX This study was supported by National Institutes of Health (NIH)-National Heart, Lung, and Blood Institute (NHLBI) R01 HL77398 (Dr London, PI) NIH-NHLBI R01 HL103946 (Dr Cheng, PI), and NIH-NCATS UL1 TR001082 (Drs Mulvahill and Carlson). NR 25 TC 5 Z9 5 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2015 VL 4 IS 8 AR e001566 DI 10.1161/JAHA.114.001566 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3HW UT WOS:000364150900001 PM 26231842 ER PT J AU Choi, EK Park, JH Lee, JY Nam, CM Hwang, MK Uhm, JS Joung, B Ko, YG Lee, MH Lubitz, SA Ellinor, PT Pak, HN AF Choi, Eue-Keun Park, Jae Hyung Lee, Ji-Young Nam, Chung Mo Hwang, Min Ki Uhm, Jae-Sun Joung, Boyoung Ko, Young-Guk Lee, Moon-Hyoung Lubitz, Steven A. Ellinor, Patrick T. Pak, Hui-Nam TI Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success SO Journal of the American Heart Association LA English DT Article DE atrial fibrillation; catheter ablation; genetic polymorphism; phenotype; recurrence ID EXPERT CONSENSUS STATEMENT; CHROMOSOME 4Q25; SURGICAL ABLATION; FOLLOW-UP; ASSOCIATION; RISK; CATHETER; RECURRENCE; RECOMMENDATIONS; POLYMORPHISM AB Background-Genomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF. Methods and Results-We determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5 +/- 10.9 years, 67.9% paroxysmal AF) and 1068 age-and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P= 1.32x 10(-16); PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P= 2.20x 10(-11); ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P= 3.75x 10(-14); KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P= 0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation. Conclusions-SNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF-susceptibility SNPs predicted clinical recurrence after catheter ablation. C1 [Park, Jae Hyung; Lee, Ji-Young; Nam, Chung Mo; Hwang, Min Ki; Uhm, Jae-Sun; Joung, Boyoung; Ko, Young-Guk; Lee, Moon-Hyoung; Pak, Hui-Nam] Yonsei Univ Hlth Syst, Cardiovasc Genome Ctr, Seoul, South Korea. [Choi, Eue-Keun] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Pak, HN (reprint author), 50 Yonsei Ro, Seoul 120752, South Korea. EM ellinor@mgh.harvard.edu; hnpak@yuhs.ac FU National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning (MSIP) [7-2013-0362]; SNUH Research Fund [2520140060]; Korea National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2014R1A1A2A16055218]; National Institutes of Health [R01HL092577, R01HL104156, K24HL105780, HL065962, K23HL114724]; American Heart Association [13EIA14220013]; Fondation Leducq [14CVD01]; Doris Duke Charitable Foundation Clinical Scientist Development Award [2014105]; Korea Health 21 R&D Project, Ministry of Health and Welfare [A085136] FX Dr Pak is supported by a grant (A085136) from the Korea Health 21 R&D Project, Ministry of Health and Welfare, and a grant (7-2013-0362) from the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (MSIP). Dr Choi is supported by grant no 2520140060 from the SNUH Research Fund and a Korea National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2014R1A1A2A16055218). Dr Ellinor is supported by grants from the National Institutes of Health (R01HL092577, R01HL104156, K24HL105780, HL065962), the American Heart Association (13EIA14220013), and Fondation Leducq (14CVD01). Dr Lubitz is supported by a grant from the National Institutes of Health (K23HL114724) and a Doris Duke Charitable Foundation Clinical Scientist Development Award (2014105). NR 27 TC 6 Z9 7 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2015 VL 4 IS 8 AR e002046 DI 10.1161/JAHA.115.002046 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3HW UT WOS:000364150900014 PM 26272656 ER PT J AU Khazanie, P Hellkamp, AS Fonarow, GC Bhatt, DL Masoudi, FA Anstrom, KJ Heidenreich, PA Yancy, CW Curtis, LH Hernandez, AF Peterson, ED Al-Khatib, SM AF Khazanie, Prateeti Hellkamp, Anne S. Fonarow, Gregg C. Bhatt, Deepak L. Masoudi, Frederick A. Anstrom, Kevin J. Heidenreich, Paul A. Yancy, Clyde W. Curtis, Lesley H. Hernandez, Adrian F. Peterson, Eric D. Al-Khatib, Sana M. TI Association Between Comorbidities and Outcomes in Heart Failure Patients With and Without an Implantable Cardioverter-Defibrillator for Primary Prevention SO Journal of the American Heart Association LA English DT Article DE aging; defibrillation; heart failure; morbidity; mortality ID CARDIAC-RHYTHM ABNORMALITIES; DEVICE-BASED THERAPY; MEDICARE BENEFICIARIES; PRACTICE GUIDELINES; CLINICAL-PRACTICE; AMERICAN-COLLEGE; TASK-FORCE; SURVIVAL; RISK; MORTALITY AB Background-Implantable cardioverter-defibrillator (ICD) therapy is associated with improved outcomes in patients with heart failure (HF), but whether this association holds among older patients with multiple comorbid illnesses and worse HF burden remains unclear. Methods and Results-Using the National Cardiovascular Data Registry's ICD Registry and the Get With The Guidelines-Heart Failure (GWTG-HF) registry linked with Medicare claims, we examined outcomes associated with primary-prevention ICD versus no ICD among HF patients aged >= 65 years in clinical practice. We included patients with an ejection fraction <= 35% who received (ICD Registry) and who did not receive (GWTG-HF) an ICD. Compared with patients with an ICD, patients in the non-ICD group were older and more likely to be female and white. In matched cohorts, the 3-year adjusted mortality rate was lower in the ICD group versus the non-ICD group (46.7% versus 55.8%; adjusted hazard ratio [HR] 0.76; 95% CI 0.69 to 0.83). There was no associated difference in all-cause readmission (HR 0.99; 95% CI 0.92 to 1.08) but a lower risk of HF readmission (HR 0.88; 95% CI 0.80 to 0.97). When compared with no ICD, ICDs were also associated with better survival in patients with <= 3 comorbidities (HR 0.77; 95% CI 0.69 to 0.87) and >3 comorbidities (HR 0.77; 95% CI 0.64 to 0.93) and in patients with no hospitalization for HF (HR 0.75; 95% CI 0.65 to 0.86) and at least 1 prior HF hospitalization (HR 0.69; 95% CI 0.58 to 0.82). In subgroup analyses, there were no interactions between ICD and mortality risk for comorbidity burden (P=0.95) and for prior HF hospitalization (P=0.46). Conclusion-Among older HF patients, ICDs for primary prevention were associated with lower risk of mortality even among those with high comorbid illness burden and prior HF hospitalization. C1 [Khazanie, Prateeti; Hellkamp, Anne S.; Anstrom, Kevin J.; Curtis, Lesley H.; Hernandez, Adrian F.; Peterson, Eric D.; Al-Khatib, Sana M.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Khazanie, Prateeti; Anstrom, Kevin J.; Curtis, Lesley H.; Hernandez, Adrian F.; Peterson, Eric D.; Al-Khatib, Sana M.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA USA. [Masoudi, Frederick A.] Univ Colorado, Aurora, CO USA. [Heidenreich, Paul A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Yancy, Clyde W.] Northwestern Univ, Chicago, IL 60611 USA. RP Al-Khatib, SM (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM alkha001@mc.duke.edu FU National Heart, Lung, and Blood Institute [1R01-HL093071-01A1, T32HL069749] FX This analysis was funded by a grant (1R01-HL093071-01A1) from the National Heart, Lung, and Blood Institute. Dr Khazanie was supported, in part, by grant T32HL069749 from the National Heart, Lung, and Blood Institute. The National Heart, Lung, and Blood Institute had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript. NR 22 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2015 VL 4 IS 8 AR e002061 DI 10.1161/JAHA.115.002061 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3HW UT WOS:000364150900016 PM 26251283 ER PT J AU Mochari-Greenberger, H Xian, Y Hellkamp, AS Schulte, PJ Bhatt, DL Fonarow, GC Saver, JL Reeves, MJ Schwamm, LH Smith, EE AF Mochari-Greenberger, Heidi Xian, Ying Hellkamp, Anne S. Schulte, Phillip J. Bhatt, Deepak L. Fonarow, Gregg C. Saver, Jeffrey L. Reeves, Mathew J. Schwamm, Lee H. Smith, Eric E. TI Racial/Ethnic and Sex Differences in Emergency Medical Services Transport Among Hospitalized US Stroke Patients: Analysis of the National Get With The Guidelines-Stroke Registry SO Journal of the American Heart Association LA English DT Article DE disparities; emergency medical services; race/ethnicity; sex; stroke ID AMERICAN-HEART-ASSOCIATION; ACUTE ISCHEMIC-STROKE; HEALTH-CARE PROFESSIONALS; ETHNIC DISPARITIES; SEEKING TREATMENT; SYMPTOMS; OUTCOMES; DELAY; ATTACK; EPIDEMIOLOGY AB Background -Differences in activation of emergency medical services (EMS) may contribute to racial/ethnic and sex disparities in stroke outcomes. The purpose of this study was to determine whether EMS use varied by race/ethnicity and sex among a current, diverse national sample of hospitalized acute stroke patients. Methods and Results-We analyzed data from 398 798 stroke patients admitted to 1613 Get With The Guidelines-Stroke participating hospitals between October 2011 and March 2014. Multivariable logistic regression was used to evaluate the associations between combinations of racial/ethnic and sex groups with EMS use, adjusting for potential confounders including demographics, medical history, and stroke symptoms. Patients were 50% female, 69% white, 19% black, 8% Hispanic, 3% Asian, and 1% other, and 86% had ischemic stroke. Overall, 59% of stroke patients were transported to the hospital by EMS. White women were most likely to use EMS (62%); Hispanic men were least likely to use EMS (52%). After adjustment for patient characteristics, Hispanic and Asian men and women had 20% to 29% lower adjusted odds of using EMS versus their white counterparts; black women were less likely than white women to use EMS (odds ratio 0.75, 95% CI 0.72 to 0.77). Patients with weakness or paresis, altered level of consciousness, and/or aphasia were significantly more likely to use EMS than patients without each symptom; the observed racial/ethnic and sex differences in EMS use remained significant after adjustment for stroke symptoms. Conclusions-EMS use differed by race/ethnicity and sex. These contemporary data document suboptimal use of EMS transport among US stroke patients, especially by racial/ethnic minorities and those with less recognized stroke symptoms. C1 [Mochari-Greenberger, Heidi] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Xian, Ying; Hellkamp, Anne S.; Schulte, Phillip J.] Duke Clin Res Inst, Durham, NC USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Fonarow, Gregg C.; Saver, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. RP Mochari-Greenberger, H (reprint author), Columbia Univ, Med Ctr, Dept Med Prevent Cardiol, 51 Audubon Ave,Suite 506, New York, NY 10032 USA. EM hm2028@columbia.edu FU Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; Janssen Pharmaceutical Company of American Heart Association Pharmaceutical Roundtable; Janssen Pharmaceutical Company of Johnson Johnson FX The Get With The Guidelines-Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, Janssen Pharmaceutical Companies of Johnson & Johnson and the American Heart Association Pharmaceutical Roundtable. NR 40 TC 1 Z9 1 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2015 VL 4 IS 8 AR e002099 DI 10.1161/JAHA.115.002099 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3HW UT WOS:000364150900019 PM 26268882 ER PT J AU Sepulveda-Crespo, D Serramia, MJ Tager, AM Vrbanac, V Gomez, R De la Mata, FJ Jimenez, JL Munoz-Fernandez, MA AF Sepulveda-Crespo, Daniel Jesus Serramia, Maria Tager, Andrew M. Vrbanac, Vladimir Gomez, Rafael Javier De la Mata, Francisco Jimenez, Jose Luis Angeles Munoz-Fernandez, Ma TI Prevention vaginally of HIV-1 transmission in humanized BLT mice and mode of antiviral action of polyanionic carbosilane dendrimer G2-S16 SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Carbosilane dendrimer; HIV-1 prevention; Humanized BLT mice; Microbicide; Nanotechnology ID HUMAN-IMMUNODEFICIENCY-VIRUS; APTAMER-SIRNA CHIMERAS; TOPICAL MICROBICIDES; PRODUCTIVE INFECTION; DRUG-DELIVERY; T-CELLS; DC-SIGN; TYPE-1; VISUALIZATION; COMBINATION AB The development of a safe, effective, and low-priced topical microbicide to prevent HIV-1 sexual transmission is urgently needed. The emerging field of nanotechnology plays an important role in addressing this challenge. We demonstrate that topical vaginal administration of 3% G2-S16 prevents HIV-1JR-CSF transmission in humanized (h)-BLT mice in 84% with no presence of HIV-1 RNA and vaginal lesions. Second-generation polyanionic carbosilane dendrimer G2-S16 with silica core and 16 sulfonate end-groups exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4 interaction, acting on the virus, and inhibiting the cell-to-cell HIV-1 transmission, confirming its multifactorial and non-specific ability. This study represents the first demonstration that transmission of HIV-1 can be efficiently blocked by vaginally applied G2-S16 in h-BLT mice. These findings provide a step forward in the development of G2-S16-based vaginal microbicides to prevent vaginal HIV-1 transmission in humans. (C) 2015 Elsevier Inc. All rights reserved. C1 [Sepulveda-Crespo, Daniel; Jesus Serramia, Maria; Angeles Munoz-Fernandez, Ma] Hosp Gen Gregorio Maranon, CIBER BBN, Spanish HIV HGM Biobank, Lab InmunoBiol Mol,IISGM, Madrid, Spain. [Sepulveda-Crespo, Daniel; Jesus Serramia, Maria; Jimenez, Jose Luis; Angeles Munoz-Fernandez, Ma] Hosp Gen Gregorio Maranon, CIBER BBN, IISGM, Plataforma Lab, Madrid, Spain. [Tager, Andrew M.; Vrbanac, Vladimir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Tager, Andrew M.; Vrbanac, Vladimir] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Gomez, Rafael; Javier De la Mata, Francisco] Univ Alcala de Henares, CIBER BBN, Dept Quim Inorgan, Madrid, Spain. RP Jimenez, JL (reprint author), IISGM, CIBER BBN, HGUGM, Lab InmunoBiol Mol, C Dr Esquerdo 46, Madrid 28007, Spain. EM joseluis.jimenez@salud.madrid.org; mmunoz.hgugm@gmail.com FU part of the Plan Nacional R + D + I; ISCIII-FEDER [PT13/0010/0028]; FIS [PI13/02016, PI14/00882]; MIMECO [CTQ2011-23245]; FIPSE; CAM [S-2010/BMD-2351, S-2010/BMD-2332]; PENTA; CYTED [214RT0482]; Programa de Investigacion de la Consejeria de Sanidad de la CAM; VI National RDi Plan; IniciativaIngenio; Consolider Program; CIBER Actions; ISCIII with European Regional Development Fund; Harvard University Center for AIDS Research [NIH P30 AI060354]; Massachusetts G. Hospital; [RD12/0017/0037] FX This work has been funded by RD12/0017/0037, project as part of the Plan Nacional R + D + I and cofinanced by ISCIII-FEDER, PT13/0010/0028, FIS (PI13/02016; PI14/00882), CTQ2011-23245 (MIMECO), FIPSE, CAM (S-2010/BMD-2351; S-2010/BMD-2332], PENTA, CYTED 214RT0482 and the "Programa de Investigacion de la Consejeria de Sanidad de la CAM" to JLJ. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, IniciativaIngenio 2010, the Consolider Program, and CIBER Actions and financed by the ISCIII with assistance from the European Regional Development Fund. The MGH Humanized Mouse Program (V.V. and A.M.T.) is partially supported by the Harvard University Center for AIDS Research (NIH P30 AI060354) and the Massachusetts G. Hospital. NR 36 TC 11 Z9 11 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD AUG PY 2015 VL 11 IS 6 BP 1299 EP 1308 DI 10.1016/j.nano.2015.04.013 PG 10 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA CV7DN UT WOS:000364432700001 PM 25959924 ER PT J AU Wilcox, SR Saia, MS Waden, H McGahn, SJ Frakes, M Wedel, SK Richards, JB AF Wilcox, Susan R. Saia, Mark S. Waden, Heather McGahn, Susan J. Frakes, Michael Wedel, Suzanne K. Richards, Jeremy B. TI Medication Administration in Critical Care Transport of Adult Patients with Hypoxemic Respiratory Failure SO PREHOSPITAL AND DISASTER MEDICINE LA English DT Article DE intravenous infusions; medication systems; pumps, infusion; transportation of patients ID CRITICAL EVENTS; ERRORS AB Introduction: Critical care transport (CCT) teams must manage a wide array of medications before and during transport. Appreciating the medications required for transport impacts formulary development as well as staff education and training. Problem: As there are few data describing the patterns of medication administration, this study quantifies medication administrations and patterns in a series of adult CCTs. Methods: This was a retrospective review of medication administration during CCTs of patients with severe hypoxemic respiratory failure from October 2009 through December 2012 from referring hospitals to three tertiary care hospitals. Results: Two hundred thirty-nine charts were identified for review. Medications were administered by the CCT team to 98.7% of these patients, with only three patients not receiving any medications from the team. Fifty-nine medications were administered in total with 996 instances of administration. Fifteen drugs were each administered to only one patient. The mean number of medications per patient was 4.2 (SD = 1.8) with a mean of 1.9 (SD = 1.1) drug infusions per patient. Conclusions: These results demonstrate that, even within a relatively homogeneous population of patients transferred with hypoxemic respiratory failure, a wide range of medications were administered. The CCT teams frequently initiated, titrated, and discontinued continuous infusions, in addition to providing numerous doses of bolused medications. C1 [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Wilcox, Susan R.; Saia, Mark S.; Waden, Heather; McGahn, Susan J.; Frakes, Michael; Wedel, Suzanne K.] Boston MedFlight, Bedford, MA USA. [Richards, Jeremy B.] Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Dept Internal Med, Boston, MA 02215 USA. RP Wilcox, SR (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM susanrwilcoxmd@gmail.com NR 11 TC 1 Z9 1 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1049-023X EI 1945-1938 J9 PREHOSPITAL DISASTER JI Prehospital Disaster Med. PD AUG PY 2015 VL 30 IS 4 BP 431 EP 435 DI 10.1017/S1049023X1500494X PG 5 WC Emergency Medicine SC Emergency Medicine GA CW0VU UT WOS:000364708700018 PM 26178583 ER PT J AU Waltz, P Escobar, D Botero, AM Zuckerbraun, BS AF Waltz, Paul Escobar, Daniel Botero, Ana Maria Zuckerbraun, Brian S. TI Nitrate/Nitrite as Critical Mediators to Limit Oxidative Injury and Inflammation SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE SYNTHASE; ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; PROTEIN-TYROSINE NITRATION; S-NITROSOTHIOL TRANSPORT; MITOCHONDRIAL COMPLEX-I; GASTRIC-MUCOSAL INJURY; REGIONAL BLOOD-FLOW; DIETARY NITRATE AB Significance: Nitric oxide (NO) is a critical signaling molecule marked by complex chemistry and varied biological responses depending on the context of the redox environment. In the setting of inflammation, NO can not only contribute to tissue injury and be causative of oxidative damage but can also signal as an adaptive molecule to limit inflammatory signaling in multiple cell types and tissues. Recent Advances: An advance in our understanding of NO biology was the recognition of the nitrate-nitrite-NO axis, whereby nitrate (predominantly from dietary sources) could be converted to nitrite and nitrite could be reduced to NO. Critical Issues: Intriguingly, the recognition of multiple enzymes that serve as nitrite reductases in the setting of hypoxia or ischemia established the concept of nitrite as a circulating endocrine reservoir of NO, with the selective release of NO at sites that were primed for this reaction. This review highlights the anti-inflammatory roles of nitrite in numerous clinical conditions, including ischemia/reperfusion, transplant, cardiac arrest, and vascular injury, and in gastrointestinal inflammation. Future Directions: These preclinical and clinical investigations set up further clinical trials and studies that elucidate the endogenous role this pathway plays in protection against inflammatory signaling. Antioxid. Redox Signal. 23, 328-339. C1 [Waltz, Paul; Escobar, Daniel; Botero, Ana Maria; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Zuckerbraun, Brian S.] Univ Pittsburgh, Ctr Crit Care Nephrol, Pittsburgh, PA USA. [Zuckerbraun, Brian S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, Dept Surg, F1267 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu FU NIGMS NIH HHS [R01 GM082830] NR 111 TC 3 Z9 4 U1 5 U2 13 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD AUG 1 PY 2015 VL 23 IS 4 BP 328 EP 339 DI 10.1089/ars.2015.6256 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CU9VU UT WOS:000363895200004 PM 26140517 ER PT J AU Handrakis, JP Liu, SA Rosado-Rivera, D Krajewski, M Spungen, AM Bang, C Swonger, K Bauman, WA AF Handrakis, John P. Liu, Shou-An Rosado-Rivera, Dwindally Krajewski, Megan Spungen, Ann M. Bang, Charlene Swonger, Kirsten Bauman, William A. TI Effect of Mild Cold Exposure on Cognition in Persons with Tetraplegia SO JOURNAL OF NEUROTRAUMA LA English DT Article DE cognitive function; human studies; hypothermia; traumatic spinal cord injury ID SPINAL-CORD-INJURY; BODY-TEMPERATURE; PERFORMANCE; THERMOREGULATION; HYPOTHERMIA; EXERCISE; HUMANS; COMPLICATIONS; IMPAIRMENT; RESPONSES AB Persons with a cervical spinal cord injury (SCI) have impaired thermoregulatory mechanisms secondary to interrupted of motor, sensory, and sympathetic pathways. In this study, our primary aim was to determine the effect of cool temperature exposure on core body temperature (Tcore) and cognitive performance in persons with tetraplegia. Seven men with chronic tetraplegia (C3-C7, American Spinal Injury Association Impairment Scale [AIS] A-C) and seven able-bodied controls were exposed to 27 degrees C temperature at baseline (BL) before being exposed to 18 degrees C for 120min (Cool Challenge). Rectal temperature (Tcore), distal skin temperatures (Tsk(avg)), microvascular skin perfusion (LDFavg), and systolic blood pressure (SBP) were measured. Cognitive performance was assessed using Delayed Recall, Stroop Interference tests at the end of BL and Cool Challenge. After Cool Challenge, Tcore decreased -1.2 +/- 0.12 degrees C (p<0.0001) in tetraplegics after an average of 109 +/- 15.9min with no change in controls after 120min. Tsk(avg) declined in both groups, but decline was less in tetraplegics than in controls (-8.6 +/- 5.8% vs. -31.6 +/- 7.9%, respectively; p<0.0001). LDFavg declined only in controls (-72 +/- 17.9%; p<0.001). Plasma norepinephrine levels differed after Cool Challenge (tetraplegics vs. controls: 86 +/- 62pg/mL vs. 832 +/- 431pg/mL, respectively; p<0.01). SBP increased from BL to Cool Challenge only in controls (123 +/- 16mm Hg to 149 +/- 17mm Hg, respectively; p<0.01). Delayed Recall and Stroop Interference scores both declined in tetraplegics (-55 +/- 47.4%; p<0.05 and -3.9 +/- 3.8%; p<0.05, respectively), but not in controls. We conclude that persons with tetraplegia lack adequate thermoregulatory mechanisms to prevent downward drift in Tcore on exposure to cool temperatures. This decline in Tcore was associated with deterioration of working memory and executive function. C1 [Handrakis, John P.; Liu, Shou-An; Rosado-Rivera, Dwindally; Krajewski, Megan; Spungen, Ann M.; Swonger, Kirsten; Bauman, William A.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Dept Vet Affairs Rehabil Res & Dev Serv, Bronx, NY 10468 USA. [Spungen, Ann M.; Bang, Charlene; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Spungen, Ann M.; Bang, Charlene; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Spungen, Ann M.; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Handrakis, John P.; Liu, Shou-An; Krajewski, Megan] New York Inst Technol, Sch Hlth Profess, Dept Phys Therapy, Old Westbury, NY 11568 USA. RP Handrakis, JP (reprint author), James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Dept Vet Affairs Rehabil Res & Dev Serv, 130 West Kingsbridge Rd,7A-13, Bronx, NY 10468 USA. EM john.handrakis@va.gov FU Department of Veterans Affairs Rehabilitation Research and Development Service National Center of Excellence for the Medical Consequences of Spinal Cord Injury [B4162-C]; James J. Peters Veterans Affairs Medical Center FX Support for this work was provided by the Department of Veterans Affairs Rehabilitation Research and Development Service National Center of Excellence for the Medical Consequences of Spinal Cord Injury (B4162-C) and the James J. Peters Veterans Affairs Medical Center. Clinical Trial Registration Number: NCT01822535. NR 54 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG 1 PY 2015 VL 32 IS 15 BP 1168 EP 1175 DI 10.1089/neu.2014.3719 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CV0JK UT WOS:000363936800004 PM 25531297 ER PT J AU Ding, WB Kou, JJ Meng, H Kou, Y He, ZX Cao, MH Wang, LX Bi, YY Thatte, HS Shi, JL AF Ding, Wenbo Kou, Junjie Meng, Huan Kou, Yan He, Zhangxiu Cao, Muhua Wang, Lixiu Bi, Yayan Thatte, Hemant S. Shi, Jialan TI Procoagulant activity induced by transcatheter closure of atrial septal defects is associated with exposure of phosphatidylserine on microparticles, platelets and red blood cells SO THROMBOSIS RESEARCH LA English DT Article DE transcatheter atrial septal defects closure; procoagulant; phosphatidylserine; microparticle; thrombosis ID ACTIVATION; COMPLICATIONS; ERYTHROCYTES; HYPERTENSION; COAGULATION; GENERATION; MEMBRANES; DEVICES; MARKERS AB The mechanism of hypercoagulable state following transcatheter closure of atrial septal defects (ASDs) remains unclear. We evaluated the exposure of phosphatidylserine (PS) on released microparticles (MPs) and also the cells of their origin from peripheral blood, and the associated increase in procoagulant activity (PCA) following transcatheter ASD closure. We demonstrate that PS+ MP levels were elevated immediately after device implantation (P <0.002), peaked at 24 hour (P <0.002), and persisted at high levels for 1-week post procedure (P <0.002). Flow cytometry analysis indicated that PS+ MPs were mainly derived from platelets, endothelial cells, and the red blood cells (RBCs). Concomittantly, PS+ platelet and RBC count also increased after transcatheter closure of ASDs, while PS+ leukocytes levels remained the same. Compared to the baseline, coagulation time of PS+ MPs, platelets, and RBCs at 24 hours post procedure decreased by about 18.7% (P <0.004), 21.5% (P <0.001), and 26.8% (P <0.001), respectively. Intrinsic factor Xa and prothrombinase were produced abundantly by platelets, RBCs, and MPs leading to materialization of fibrin by 24 hours. Additionally, Xase complex formation and thrombin generation was inhibited by about 74% by the addition of lactadherin to the assays. Our results thus demonstrate that PS exposure on MPs, platelets, and RBCs play an important role in hypercoagulability following transcatheter ASD closure. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Ding, Wenbo; Kou, Junjie; Meng, Huan; Kou, Yan] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. [He, Zhangxiu; Cao, Muhua; Wang, Lixiu; Bi, Yayan] Harbin Med Univ, Affiliated Hosp 1, Dept Cardiol, Harbin, Peoples R China. [He, Zhangxiu; Cao, Muhua; Shi, Jialan] Harbin Med Univ, Affiliated Hosp 1, Dept Hematol, Harbin, Peoples R China. [Thatte, Hemant S.; Shi, Jialan] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst,Dept Surg,Div Cardiotho, Boston, MA 02115 USA. RP Kou, JJ (reprint author), Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. EM junjiekou@163.com; biyayan@163.com; jialan_shi@hms.harvard.edu NR 36 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD AUG PY 2015 VL 136 IS 2 BP 354 EP 360 DI 10.1016/j.thromres.2015.06.015 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CV0PN UT WOS:000363953000029 PM 26099643 ER PT J AU Lee, SM Takemoto, S Wallace, AW AF Lee, Susan M. Takemoto, Steven Wallace, Arthur W. TI Association between Withholding Angiotensin Receptor Blockers in the Early Postoperative Period and 30-day Mortality A Cohort Study of the Veterans Affairs Healthcare System SO ANESTHESIOLOGY LA English DT Article ID CONVERTING ENZYME-INHIBITORS; ACUTE KIDNEY INJURY; VASCULAR-SURGERY; CARDIAC-SURGERY; RISK; ANTAGONISTS; DISCONTINUATION; MEDICATIONS; VARIABLES; BLOCKADE AB Background: Despite widespread use, there is limited information to guide perioperative management of angiotensin receptor blockers (ARBs). Methods: In this retrospective cohort study, the authors evaluated the patterns of postoperative ARB use in veterans regularly prescribed ARBs admitted for noncardiac surgery at the Veterans Affairs Healthcare system between 1999 and 2011. Multivariable and propensity score-matched Cox proportional hazards models were used to determine the independent effect of failure to resume ARB by postoperative day 2 on the primary outcome of all-cause 30-day mortality. Results: Out of 1,167,482 surgical admissions, 30,173 inpatient surgical admissions met inclusion criteria. Approximately 10,205 patients (33.8%) in the cohort did not resume ARB by day 2. Those that resumed ARB had a 30-day mortality rate of 1.3% (260 of 19,968), whereas 3.2% (323 of 10,205) died in the group that withheld ARB. The unadjusted hazard ratio (HR) for 30-day mortality was 2.45 (95% CI, 2.08 to 2.89; P < 0.001) for those that withheld ARB compared with those that resumed, whereas the multivariable adjusted HR was 1.74 (95% CI, 1.47 to 2.06; P < 0.001). When restricted to a propensity score-matched subset of 19,490, the HR was similar (1.47; 95% CI, 1.22 to 1.78; P < 0.001). Withholding ARB in younger patients increased mortality risk (HR = 2.52; 95% CI, 1.69 to 3.76; P < 0.001 for age <60 yr) compared with older patients (HR = 1.42; 95% CI, 1.09 to 1.85; P = 0.01 for age >75 yr). Conclusions: Postoperative delay in resuming ARB is common, particularly in patients who are frail after surgery. Withholding ARB is strongly associated with increased 30-day mortality, especially in younger patients, although residual confounding may be present. C1 [Lee, Susan M.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Lee, SM (reprint author), Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, 521 Parnassus Ave Rm C-450, San Francisco, CA 94143 USA. EM susan.lee5@va.gov FU Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California; San Francisco Veterans Affairs Medical Center Anesthesiology Service, San Francisco, California; Northern California Institute for Research and Education, San Francisco, California FX Research time for the authors was internally funded by the Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California; the San Francisco Veterans Affairs Medical Center Anesthesiology Service, San Francisco, California; and the Northern California Institute for Research and Education, San Francisco, California. NR 36 TC 8 Z9 8 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 AUG PY 2015 VL 123 IS 2 BP 288 EP 306 DI 10.1097/ALN.0000000000000739 PG 19 WC Anesthesiology SC Anesthesiology GA CU4YI UT WOS:000363537300008 PM 26200181 ER PT J AU Monk, TG Bronsert, MR Henderson, WG Mangione, MP Sum-Ping, STJ Bentt, DR Nguyen, JD Richman, JS Meguid, RA Hammermeister, KE AF Monk, Terri G. Bronsert, Michael R. Henderson, William G. Mangione, Michael P. Sum-Ping, S. T. John Bentt, Deyne R. Nguyen, Jennifer D. Richman, Joshua S. Meguid, Robert A. Hammermeister, Karl E. TI Association between Intraoperative Hypotension and Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery SO ANESTHESIOLOGY LA English DT Article ID AFFAIRS SURGICAL RISK; CARDIAC RISK; QUALITY; ANESTHESIA; CARE; ADJUSTMENT; MANAGEMENT; COMPLICATIONS; DEFINITIONS; PRESSURE AB Background: Although deviations in intraoperative blood pressure are assumed to be associated with postoperative mortality, critical blood pressure thresholds remain undefined. Therefore, the authors estimated the intraoperative thresholds of systolic blood pressure (SBP), mean blood pressure (MAP), and diastolic blood pressure (DBP) associated with increased risk-adjusted 30-day mortality. Methods: This retrospective cohort study combined intraoperative blood pressure data from six Veterans Affairs medical centers with 30-day outcomes to determine the risk-adjusted associations between intraoperative blood pressure and 30-day mortality. Deviations in blood pressure were assessed using three methods: (1) population thresholds (individual patient sum of area under threshold [AUT] or area over threshold 2 SDs from the mean of the population intraoperative blood pressure values), (2). absolute thresholds, and (3) percent change from baseline blood pressure. Results: Thirty-day mortality was associated with (1) population threshold: systolic AUT (odds ratio, 3.3; 95% CI, 2.2 to 4.8), mean AUT (2.8; 1.9 to 4.3), and diastolic AUT (2.4; 1.6 to 3.8). Approximate conversions of AUT into its separate components of pressure and time were SBP < 67 mmHg for more than 8.2min, MAP < 49 mmHg for more than 3.9min, DBP < 33 mmHg for more than 4.4min. (2) Absolute threshold: SBP < 70 mmHg for more than or equal to 5min (odds ratio, 2.9; 95% CI, 1.7 to 4.9), MAP < 49 mmHg for more than or equal to 5min (2.4; 1.3 to 4.6), and DBP < 30 mmHg for more than or equal to 5min (3.2; 1.8 to 5.5). (3) Percent change: MAP decreases to more than 50% from baseline for more than or equal to 5min (2.7; 1.5 to 5.0). Intraoperative hypertension was not associated with 30-day mortality with any of these techniques. Conclusion: Intraoperative hypotension, but not hypertension, is associated with increased 30-day operative mortality. C1 [Monk, Terri G.] Durham VA Med Ctr, Emeritus Fac, Durham, NC USA. [Monk, Terri G.] Univ Missouri, Dept Anesthesiol & Perioperat Med, Columbia, MO USA. [Bronsert, Michael R.; Henderson, William G.] ACCORDS, Aurora, CO USA. [Henderson, William G.] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Mangione, Michael P.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Sum-Ping, S. T. John] Univ Texas SW Med Ctr Dallas, VA North Texas Hlth Care Syst, Dept Anesthesiol & Pain Management, Dallas, TX 75390 USA. [Bentt, Deyne R.] George Washington Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Washington DC VA Med Ctr, Washington, DC USA. [Nguyen, Jennifer D.] Baylor Coll Med, Michael DeBakey Vet Affairs Med Ctr, Dept Anesthesiol, Houston, TX 77030 USA. [Richman, Joshua S.] Univ Alabama Birmingham, Dept Surg, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Meguid, Robert A.] Univ Colorado, Dept Surg, Sch Med, Aurora, CO USA. [Hammermeister, Karl E.] Univ Colorado, Dept Med Cardiol, Sch Med, Aurora, CO USA. RP Monk, TG (reprint author), Dept Anesthesiol & Perioperat Med, One Hosp Dr,3w-27F,DC005-00, Columbia, MO 65212 USA. EM monkt@health.missouri.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Washington, D.C. [IIR 05-229] FX This study is supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Grant Number IIR 05-229, Washington, D.C. NR 32 TC 27 Z9 27 U1 1 U2 3 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 AUG PY 2015 VL 123 IS 2 BP 307 EP 319 DI 10.1097/ALN.0000000000000756 PG 13 WC Anesthesiology SC Anesthesiology GA CU4YI UT WOS:000363537300009 PM 26083768 ER PT J AU Santer, P Pejo, E Feng, Y Chao, W Raines, DE AF Santer, Peter Pejo, Ervin Feng, Yan Chao, Wei Raines, Douglas E. TI Cyclopropyl-methoxycarbonyl Metomidate Studies in a Lipopolysaccharide Inflammatory Model of Sepsis SO ANESTHESIOLOGY LA English DT Article ID CRITICALLY-ILL PATIENTS; ADRENOCORTICAL FUNCTION; ADRENAL INSUFFICIENCY; ETOMIDATE ANALOG; UNITED-STATES; HPA AXIS; INHIBITION; MORTALITY; CYTOKINES; PITUITARY AB Background: Cyclopropyl-methoxycarbonyl metomidate (CPMM) is a rapidly metabolized etomidate analog that is currently in clinical trials. The goal of this study is to assess CPMM's potential value as an anesthetic agent for use in patients with sepsis by defining its actions in an acute inflammatory model of sepsis. Methods:Escherichia coli lipopolysaccharide (1mg/kg) was injected intravenously into Sprague-Dawley rats. Thirty minutes later, CPMM, etomidate, or vehicle (n = 8 per group) was infused for 1h. Plasma adrenocorticotropic hormone, corticosterone, and cytokine (interleukin-1, interleukin-6, interleukin-10, and tumor necrosis factor-) concentrations were measured before, during, and after infusion. Results: After lipopolysaccharide injection, adrenocorticotropic hormone concentrations changed similarly over time in all three groups. Compared with vehicle group rats, CPMM group rats had significantly lower corticosterone concentrations at only a single study time point during infusion and no significant differences in cytokine concentrations at any time during the study period. Compared with etomidate group rats, CPMM group rats had significantly higher corticosterone concentrations (up to nine-fold) during and after hypnotic infusion. Cytokine concentrations in CPMM group rats and vehicle group rats were not significantly different, but they were significantly lower than those in etomidate group rats. Postinfusion mortality was 40% in etomidate group rats and 0% in CPMM and vehicle group rats. Conclusion: Compared with etomidate, CPMM produces less adrenocortical suppression, lower plasma cytokine concentrations, and improved survival in a lipopolysaccharide inflammatory model of sepsis. These results suggest that CPMM may be a safer alternative to etomidate in patients with sepsis. C1 [Santer, Peter; Pejo, Ervin; Feng, Yan; Chao, Wei; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB444, Boston, MA 02114 USA. EM draines@partners.org OI Santer, Peter/0000-0002-1735-0774 FU National Institutes of Health, Bethesda, Maryland [R01-GM087316]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts FX Funded by grant R01-GM087316 from the National Institutes of Health, Bethesda, Maryland, and the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. NR 39 TC 2 Z9 2 U1 0 U2 2 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 AUG PY 2015 VL 123 IS 2 BP 368 EP 376 DI 10.1097/ALN.0000000000000721 PG 9 WC Anesthesiology SC Anesthesiology GA CU4YI UT WOS:000363537300015 PM 26035348 ER PT J AU Berra, L Kacmarek, RM AF Berra, L. Kacmarek, R. M. TI Is esophageal pressure monitoring essential for the most critically ill? SO MINERVA ANESTESIOLOGICA LA English DT Editorial Material ID MECHANICAL VENTILATION; LUNG INJURY C1 [Berra, L.; Kacmarek, R. M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Berra, L.; Kacmarek, R. M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kacmarek, R. M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp, Warren Bldg 1225,55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 8 TC 1 Z9 1 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 EI 1827-1596 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD AUG PY 2015 VL 81 IS 8 BP 830 EP 831 PG 2 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA CV0BZ UT WOS:000363913600003 PM 25925900 ER PT J AU van der Wilden, GM Subramanian, MP Chang, YC Lottenberg, L Sawyer, R Davies, SW Ferrada, P Han, JF Beekley, A Velmahos, GC de Moya, MA AF van der Wilden, Gwendolyn M. Subramanian, Melanie P. Chang, Yuchiao Lottenberg, Lawrence Sawyer, Robert Davies, Stephen W. Ferrada, Paula Han, Jinfeng Beekley, Alec Velmahos, George C. de Moya, Marc A. TI Antibiotic Regimen after a Total Abdominal Colectomy with Ileostomy for Fulminant Clostridium difficile Colitis: A Multi-Institutional Study SO SURGICAL INFECTIONS LA English DT Article ID PSEUDOMEMBRANOUS COLITIS; EMERGENCY COLECTOMY; METRONIDAZOLE; VANCOMYCIN; PREDICTORS; DIARRHEA; DISEASE; INFECTION; MORTALITY; SURGERY AB Background: Fulminant Clostridium difficile colitis (fCDC) is a highly lethal disease with mortality rates ranging between 12% and 80%. Although often these patients require a total abdominal colectomy (TAC) with ileostomy, there is no established management protocol for post-operative antibiotics. In this study we aim to make some recommendations for post-operative antibiotic usage, while describing the practice across different institutions. Methods: Multi-institutional retrospective case series including fCDC patients who underwent a TAC between January 1, 2007, and June 30, 2012. We first analyzed the complete cohort and consecutively performed a survivor analysis, comparing different antibiotic regimens. Additionally we stratified by time interval (antibiotics for 7d, or 8d). Primary outcome was in-hospital mortality. Additional secondary outcomes included hospital length of stay (HLOS), ICU LOS, number of ventilator-free days, and occurrence of intra-abdominal complications (proctitis, abscess, sepsis, etc.). Results: A total of 100fCDC patients that underwent a TAC were included across five institutions. Four different antibiotic regimens were compared; A (metronidazole IV+vancomycin PO), B (metronidazole IV), C (metronidazole IV+vanco PO and PR), and D (metronidazole IV+vancomycin PR). The combination of IV metronidazole with or without PO vancomycin showed superior outcomes in terms of a shorter ICU length of stay and more ventilator-free days. However, when comparing metronidazole alone vs. metronidazole and any combination of vancomycin, no significant differences were found. Neither the addition of vancomycin enema, nor the time interval changed outcomes. Conclusion: Patients, after a TAC for fCDC, may be placed on either IV metronidazole or PO vancomycin depending upon local antibiograms, and proctitis may be treated with the addition of a vancomycin enema (PR). There was no data to support routine treatment of more than 7d. C1 [van der Wilden, Gwendolyn M.; Subramanian, Melanie P.; Velmahos, George C.; de Moya, Marc A.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Crit Care, Boston, MA 02114 USA. [van der Wilden, Gwendolyn M.; Subramanian, Melanie P.; Chang, Yuchiao; Velmahos, George C.; de Moya, Marc A.] Harvard Univ, Sch Med, Boston, MA USA. [van der Wilden, Gwendolyn M.] Leiden Univ, Med Ctr, Dept Trauma Surg, Leiden, Netherlands. [van der Wilden, Gwendolyn M.] Leiden Univ, Leiden, Netherlands. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lottenberg, Lawrence] UF Hlth Sci Ctr, Dept Surg, Gainesville, FL USA. [Lottenberg, Lawrence] Univ Florida, Coll Med, Gainesville, FL USA. [Sawyer, Robert; Davies, Stephen W.] Univ Virginia Hlth Syst, Dept Surg, Charlottesville, VA USA. [Sawyer, Robert; Davies, Stephen W.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Ferrada, Paula; Han, Jinfeng] VCU Med Ctr, Dept Surg, Richmond, VA USA. [Ferrada, Paula; Han, Jinfeng] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. [Beekley, Alec] Thomas Jefferson Univ Hosp, Dept Surg, Philadelphia, PA 19107 USA. [Beekley, Alec] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP de Moya, MA (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Crit Care, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM mdemoya@partners.org FU NIAID NIH HHS [T32 AI078875] NR 30 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-2964 EI 1557-8674 J9 SURG INFECT JI Surg. Infect. PD AUG 1 PY 2015 VL 16 IS 4 BP 455 EP 460 DI 10.1089/sur.2013.153 PG 6 WC Infectious Diseases; Surgery SC Infectious Diseases; Surgery GA CU9PJ UT WOS:000363876400016 PM 26069992 ER PT J AU Dolbow, DR Gorgey, AS Recio, AC Stiens, SA Curry, AC Sadowsky, CL Gater, DR Martin, R McDonald, JW AF Dolbow, David R. Gorgey, Ashraf S. Recio, Albert C. Stiens, Steven A. Curry, Amanda C. Sadowsky, Cristina L. Gater, David R. Martin, Rebecca McDonald, John W. TI Activity-Based Restorative Therapies after Spinal Cord Injury: Inter-institutional conceptions and perceptions SO AGING AND DISEASE LA English DT Review DE Neuroplasticity; Massed practice; Locomotor Training; Task-specific Practice; Activity-based Restorative Therapies ID FUNCTIONAL ELECTRICAL-STIMULATION; BONE-MINERAL DENSITY; CARDIOVASCULAR-DISEASE; PROGENITOR CELLS; BODY-COMPOSITION; INDIVIDUALS; EXERCISE; RECOVERY; NEUROREHABILITATION; QUADRIPLEGIA AB This manuscript is a review of the theoretical and clinical concepts provided during an inter-institutional training program on Activity-Based Restorative Therapies (ABRT) and the perceptions of those in attendance. ABRT is a relatively recent high volume and intensity approach toward the restoration of neurological deficits and decreasing the risk of secondary conditions associated with paralysis after spinal cord injury (SCI). ABRT is guided by the principle of neuroplasticity and the belief that even those with chronic SCI can benefit from repeated activation of the spinal cord pathways located both above and below the level of injury. ABRT can be defined as repetitive-task specific training using weight-bearing and external facilitation of neuromuscular activation. The five key components of ABRT are weight-bearing activities, functional electrical stimulation, task-specific practice, massed practice and locomotor training which includes body weight supported treadmill walking and water treadmill training. The various components of ABRT have been shown to improve functional mobility, and reverse negative body composition changes after SCI leading to the reduction of cardiovascular and other metabolic disease risk factors. The consensus of those who received the ABRT training was that ABRT has much potential for enhancement of recovery of those with SCI. Although various institutions have their own strengths and challenges, each institution was able to initiate a modified ABRT program. C1 [Dolbow, David R.] Univ So Mississippi, Coll Hlth Human Performance & Recreat, Hattiesburg, MS 39406 USA. [Gorgey, Ashraf S.] Hunter Holmes McGuire VA Med Ctr, Spinal Cord Injury & Disorders Ctr, Richmond, VA 23224 USA. [Gorgey, Ashraf S.] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23298 USA. [Recio, Albert C.; Sadowsky, Cristina L.; Martin, Rebecca; McDonald, John W.] Kennedy Krieger Inst, Int Ctr Spinal Cord Injury, Baltimore, MD 21205 USA. [Recio, Albert C.; Sadowsky, Cristina L.; McDonald, John W.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Stiens, Steven A.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Curry, Amanda C.] VA Boston Healthcare Syst, Phys Med & Rehabil, West Roxbury, MA 02132 USA. [Gater, David R.] Penn State Hershey Med Ctr & Hlth Syst, Hershey, PA 17033 USA. [Gater, David R.] Penn State Coll Med, Hershey, PA 17033 USA. RP Dolbow, DR (reprint author), Univ So Mississippi, 118 Coll Dr,5142, Hattiesburg, MS 39406 USA. EM David.Dolbow@usm.edu FU Department of Defense FX The ABRT Inter-Institutional training program held at the International Center for Spinal Injury at Kennedy Krieger Institute was funded by a grant from the Department of Defense. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. NR 60 TC 1 Z9 1 U1 2 U2 7 PU INT SOC AGING & DISEASE PI FORT WORTH PA EDITORIAL OFF, 3400 CAMP BOWIE BLVD, FORT WORTH, TX 76106 USA SN 2152-5250 J9 AGING DIS JI Aging Dis. PD AUG PY 2015 VL 6 IS 4 BP 254 EP 261 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA CU3LK UT WOS:000363426600004 PM 26236547 ER PT J AU Doron, S Hibberd, PL Goldin, B Thorpe, C McDermott, L Snydman, DR AF Doron, Shira Hibberd, Patricia L. Goldin, Barry Thorpe, Cheleste McDermott, Laura Snydman, David R. TI Effect of Lactobacillus rhamnosus GG Administration on Vancomycin-Resistant Enterococcus Colonization in Adults with Comorbidities SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BACTEREMIA; DIARRHEA; PROBIOTICS; CHILDREN; THERAPY AB Vancomycin-resistant enterococci (VRE) are endemic in health care settings. These organisms colonize the gastrointestinal tract and can lead to infection which is associated with increased mortality. There is no treatment for VRE colonization. We conducted a randomized, double-blind, placebo-controlled clinical trial to examine the safety and efficacy of administration of the probiotic Lactobacillus rhamnosus GG (LGG) for the reduction or elimination of intestinal colonization by VRE. Colonized adults were randomized to receive LGG or placebo for 14 days. Quantitative stool cultures for LGG and VRE were collected at baseline and days 7, 14, 21, 28, and 56. Day 14 stool samples from some subjects were analyzed by quantitative PCR (qPCR) for LGG. Patients were closely monitored for adverse events. Eleven subjects, of whom 5 received LGG and 6 received placebo, were analyzed. No differences in VRE colony counts were seen at any time points between groups. No decline in colony counts was seen over time in subjects who received LCC. LGG was detected by PCR in all samples tested from subjects who received LCC but was only isolated in culture from 2 of 5 subjects in the LCC group. No treatment-related adverse events were seen. We demonstrated that LCC could be administered safely to patients with comorbidities and is recoverable in some patients' stool cultures. Concomitant administration of antibiotics may have resulted in an inability to recover viable organisms from stool samples, but LCC DNA could still be detected by qPCR. LCC administration did not affect VRE colonization in this study. (This study was registered at Clinicaltrials.gov under registration no. NCT00756262.) C1 [Doron, Shira; Thorpe, Cheleste; McDermott, Laura; Snydman, David R.] Tufts Med Ctr, Div Infect Dis, Boston, MA 02111 USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Div Global Hlth, Boston, MA 02114 USA. [Goldin, Barry] Tufts Univ, Sch Med, Dept Publ Hlth & Commun Med, Boston, MA 02111 USA. RP Doron, S (reprint author), Tufts Med Ctr, Div Infect Dis, Boston, MA 02111 USA. EM sdoron@tuftsmedicalcenter.org RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 FU National Institutes of Health [UL1 RR025752, UL1 TR000073]; National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health [UO1 AT 001892, K23 AT 003391] FX The Tufts Clinical and Translational Science Institute core lab processed samples for this study and was supported by the National Institutes of Health (UL1 RR025752 and UL1 TR000073).; This work was supported by the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (UO1 AT 001892 and K23 AT 003391). We appreciate the guidance provided by the Office of Clinical and Regulatory Affairs of the National Center for Complementary and Alternative Medicine and program officer Linda Duffy. NR 24 TC 2 Z9 3 U1 1 U2 4 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 AUG PY 2015 VL 59 IS 8 BP 4593 EP 4599 DI 10.1128/AAC.00300-15 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CT6VY UT WOS:000362952000033 PM 26014940 ER PT J AU Kwak, YG Jacoby, GA Hooper, DC AF Kwak, Yee Gyung Jacoby, George A. Hooper, David C. TI Effect of Qnr on Plasmid Gyrase Toxins CcdB and ParE SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MEDIATED QUINOLONE RESISTANCE; PREVALENCE; PROTEIN AB Plasmid toxins CcdB and ParE are part of addiction systems promoting plasmid maintenance. Both target host DNA gyrase, as do quinolones and plasmid-determined Qnr proteins that protect gyrase from quinolone inhibition. We cloned qnrB4, qnrS1, ccdB, parE, and the antitoxin-encoding genes ccdA and parD on compatible plasmids and tested them in combination. CcdB and ParE had no specific effect on quinolone susceptibility or Qnr protection, and Qnr did not act as a CcdB or ParE antitoxin. C1 [Kwak, Yee Gyung; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kwak, Yee Gyung] Inje Univ, Coll Med, Busan, South Korea. [Jacoby, George A.] Lahey Hosp & Med Ctr, Burlington, MA 01805 USA. RP Jacoby, GA (reprint author), Lahey Hosp & Med Ctr, Burlington, MA 01805 USA. EM george.a.jacoby@lahey.org FU Inje Research and Scholarship Foundation from Inje University College of Medicine; National Institutes of Health, U.S. Public Health Service [R01 AI057576] FX This work was supported by the Inje Research and Scholarship Foundation in 2011 (Y.G.K.) from the Inje University College of Medicine and by grant R01 AI057576 (to D.C.H. and G.A.J.) from the National Institutes of Health, U.S. Public Health Service. NR 14 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 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2015 VL 59 IS 8 BP 5078 EP 5079 DI 10.1128/AAC.00524-15 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CT6VY UT WOS:000362952000101 PM 26055367 ER PT J AU Cortes, ARG Abdala, R Weber, M Arita, ES Ackerman, JL AF Cortes, A. R. G. Abdala-Junior, R. Weber, M. Arita, E. S. Ackerman, J. L. TI Influence of pulse sequence parameters at 1.5 T and 3.0 T on MRI artefacts produced by metal-ceramic restorations SO DENTOMAXILLOFACIAL RADIOLOGY LA English DT Article DE metal-ceramic restorations; magnetic resonance imaging; artifact; pulse sequence ID MAGNETIC-SUSCEPTIBILITY; IMAGING ARTIFACTS; DENTAL MATERIALS; IMPLANTS; IMPACT AB Objectives: Susceptibility artefacts from dental materials may compromise MRI diagnosis. However, little is known regarding MRI artefacts of dental material samples with the clinical shapes used in dentistry. The present phantom study aims to clarify how pulse sequences and sequence parameters affect MRI artefacts caused by metal ceramic restorations. Methods: A phantom consisting of nickel chromium metal ceramic restorations (i.e. dental crowns and fixed bridges) and cylindrical reference specimens immersed in agar gel was imaged in 1.5 and 3.0 T MRI scanners. Gradient echo (GRE), spin echo (SE) and ultrashort echo time (UTE) pulse sequences were used. The artefact area in each image was automatically calculated from the pixel values within a region of interest. Mean values for similar pulse sequences differing in one parameter at a time were compared. A comparison between mean artefact area at 1.5 and 3.0 T, and from GRE and SE was also carried out. In addition, a parametric correlation between echo time (TE) and artefact area was performed. Results: A significant correlation was found between TE and artefact area in GRE images. Higher receiver bandwidth significantly reduced artefact area in SE images. UTE images yielded the smallest artefact area at 1.5 T. In addition, a significant difference in mean artefact area was found between images at 1.5 and 3.0 T field strengths (p = 0.028) and between images from GRE and SE pulse sequences (p = 0.005). Conclusions: It is possible to compensate the effect of higher field strength on MRI artefacts by setting optimized pulse sequences for scanning patients with metal ceramic restorations. C1 [Cortes, A. R. G.; Ackerman, J. L.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Cortes, A. R. G.; Ackerman, J. L.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Abdala-Junior, R.; Weber, M.; Arita, E. S.] Univ Sao Paulo, Sch Dent, Dept Stomatol, Sao Paulo, Brazil. RP Cortes, ARG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM acortes@nmr.mgh.harvard.edu RI Cortes, Arthur/C-8738-2013 OI Cortes, Arthur/0000-0001-6591-7256 FU National Council for Scientific and Technological Development CNPq-Science Without Borders, Brazil [232643/2013-0]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health FX RGC gratefully acknowledges post-doctoral scholarship grant number 232643/2013-0 from the National Council for Scientific and Technological Development CNPq-Science Without Borders, Brazil. This research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41 EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. NR 19 TC 0 Z9 0 U1 1 U2 2 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0250-832X EI 1476-542X J9 DENTOMAXILLOFAC RAD JI Dentomaxillofac. Radiol. PD AUG PY 2015 VL 44 IS 8 AR 20150136 DI 10.1259/dmfr.20150136 PG 5 WC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging SC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging GA CU2OV UT WOS:000363363700007 PM 26084475 ER PT J AU Lee, J Adelmant, G Marto, JA Lee, DH AF Lee, Jihye Adelmant, Guillaume Marto, Jarrod A. Lee, Dong-Hyun TI Dephosphorylation of DBC1 by Protein Phosphatase 4 Is Important for p53-Mediated Cellular Functions SO MOLECULES AND CELLS LA English DT Article DE deleted in breast cancer-1; depho-sphorylation; DNA damage response; protein phosphatase 4 ID DNA-DAMAGE RESPONSE; ANALYSIS REVEALS; BREAST-CANCER; SIRT1; PP4; REGULATOR; COMPLEX; APOPTOSIS; ENABLES; REPAIR AB Deleted in breast cancer-1 (DBC1) contributes to the regulation of cell survival and apoptosis. Recent studies demonstrated that DBC is phosphorylated at Thr454 by ATM/ATR kinases in response to DNA damage, which is a critical event for p53 activation and apoptosis. However, how DBC1 phosphorylation is regulated has not been studied. Here we show that protein phosphatase 4 (PP4) dephosphorylates DBC1, regulating its role in DNA damage response. PP4R2, a regulatory subunit of PP4, mediates the interaction between DBC1 and PP4C, a catalytic subunit. PP4C efficiently dephosphorylates pThr454 on DBC1 in vitro, and the depletion of PP4C/PP4R2 in cells alters the kinetics of DBC1 phosphorylation and p53 activation, and increases apoptosis in response to DNA damage, which are compatible with the expression of the phosphomimetic DBC-1 mutant (T454E). These suggest that the PP4-mediated dephosphorylation of DBC1 is necessary for efficient damage responses in cells. C1 [Lee, Jihye; Lee, Dong-Hyun] Chonnam Natl Univ, Dept Biol Sci, Coll Sci, Kwangju 500757, South Korea. [Adelmant, Guillaume; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Canc Biol, Dept Biol Chem Mol Pharmacol, Boston, MA 02115 USA. [Adelmant, Guillaume; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. RP Lee, DH (reprint author), Chonnam Natl Univ, Dept Biol Sci, Coll Sci, Kwangju 500757, South Korea. EM donghyunlee73@jnu.ac.kr FU Basic Science Research Program through the National Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2013R1A1A1061207]; Chonnam National University FX The Flag-DBC1 construct was a gift from J.E. Kim (Kyung Hee University). This study was supported by grants from Basic Science Research Program through the National Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2013R1A1A1061207), and Chonnam National University, 2014. NR 26 TC 2 Z9 2 U1 0 U2 1 PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY PI SEOUL PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 EI 0219-1032 J9 MOL CELLS JI Mol. Cells PD AUG PY 2015 VL 38 IS 8 BP 697 EP 704 DI 10.14348/molcells.2015.0066 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CU2VJ UT WOS:000363381400004 ER PT J AU Evans, JR Zhao, S Daignault, S Sanda, MG Michalski, J Sandler, HM Kuban, DA Ciezki, J Kaplan, ID Zietman, AL Hembroff, L Feng, FY Suy, S Skolarus, TA McLaughlin, PW Wei, JT Dunn, RL Finkelstein, SE Mantz, CA Collins, SP Hamstra, DA AF Evans, Joseph R. Zhao, Shuang Daignault, Stephanie Sanda, Martin G. Michalski, Jeff Sandler, Howard M. Kuban, Deborah A. Ciezki, Jay Kaplan, Irving D. Zietman, Anthony L. Hembroff, Larry Feng, Felix Y. Suy, Simeng Skolarus, Ted A. McLaughlin, Patrick W. Wei, John T. Dunn, Rodney L. Finkelstein, Steven E. Mantz, Constantine A. Collins, Sean P. Hamstra, Daniel A. . CA PROSTQA Study Consortium TI Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Prostate cancer; Stereotactic body radiotherapy (SBRT); IMRT; Brachytherapy; Quality of life ID LOCALIZED PROSTATE-CANCER; PHASE-II TRIAL; RADIATION-THERAPY; RADICAL PROSTATECTOMY; SHORT-FORM; OUTCOMES; INDEX; EXPERIENCE; SURVIVORS; TOXICITY AB Background and purpose: Stereotactic body radiotherapy (SBRT) is being used for prostate cancer, but concerns persist about toxicity compared to other radiotherapy options. Materials and methods: We conducted a multi-institutional pooled cohort analysis of patient-reported quality of life (QOL) [EPIC-26] before and after intensity-modulated radiotherapy (IMRT), brachytherapy, or SBRT for localized prostate cancer. Data were analyzed by mean domain score, minimal clinically detectable difference (MCD) in domain score, and multivariate analyses to determine factors associated with domain scores at 2-years. Results: Data were analyzed from 803 patients at baseline and 645 at 2-years. Mean declines at 2-years across all patients were -1.9, -4.8, -4.9, and -13.3 points for urinary obstructive, urinary incontinence, bowel, and sexual symptom domains, respectively, corresponding to MCD in 29%, 20%, and 28% of patients. On multivariate analysis (vs. IMRT), brachytherapy had worse urinary irritation at 2-years (-6.8 points, p < 0.0001) but no differences in other domains (p > 0.15). QOL after SBRT was similar for urinary (p > 0.5) and sexual domains (p = 0.57), but was associated with better bowel score (+6.7 points, p < 0.0002). Conclusions: QOL 2-years after brachytherapy, IMRT, or SBRT is very good and largely similar, with small differences in urinary and bowel QOL that are likely minimized by modern techniques. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Evans, Joseph R.; Zhao, Shuang; Feng, Felix Y.; McLaughlin, Patrick W.; Hamstra, Daniel A. .] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Daignault, Stephanie] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Sanda, Martin G.] Emory Univ, Dept Urol, Atlanta, GA 30322 USA. [Michalski, Jeff] Washington Univ, Med Ctr, Dept Radiat Oncol, St Louis, MO USA. [Sandler, Howard M.] Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA. [Kuban, Deborah A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Ciezki, Jay] Cleveland Clin, Dept Radiat Oncol, Boston, MA USA. [Kaplan, Irving D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hembroff, Larry] Michigan State Univ, E Lansing, MI 48824 USA. [Suy, Simeng; Collins, Sean P.] Georgetown Univ, Washington, DC USA. [Skolarus, Ted A.; Wei, John T.; Dunn, Rodney L.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Skolarus, Ted A.] VA Ann Arbor Healthcare Syst, HSR&D Ctr Clin Management Res, Ft Myers, FL USA. [Finkelstein, Steven E.; Mantz, Constantine A.] 21st Century Oncol, Ft Myers, FL USA. RP Hamstra, DA (reprint author), Univ Michigan, Radiat Oncol, Med Sci 1, Rm 4417B,1301 Catherine St,SPC 5637, Ann Arbor, MI 48109 USA. EM dhamm@umich.edu RI Sanda, Martin/B-2023-2015 FU National Institutes of Health [R01 CA95662, RC1 CA146596, RC1 EB011001] FX PROST-QA Consortium Funded by National Institutes of Health Grants R01 CA95662, RC1 CA146596, and RC1 EB011001. The study sponsors played no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. NR 31 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD AUG PY 2015 VL 116 IS 2 BP 179 EP 184 DI 10.1016/j.radonc.2015.07.016 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CT8PE UT WOS:000363077700004 PM 26276528 ER EF