FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Carmona, R Zakeri, K Green, G Hwang, L Gulaya, S Xu, BB Verma, R Williamson, CW Triplett, DP Rose, BS Shen, HJ Vaida, F Murphy, JD Mell, LK AF Carmona, Ruben Zakeri, Kaveh Green, Garrett Hwang, Lindsay Gulaya, Sachin Xu, Beibei Verma, Rohan Williamson, Casey W. Triplett, Daniel P. Rose, Brent S. Shen, Hanjie Vaida, Florin Murphy, James D. Mell, Loren K. TI Improved Method to Stratify Elderly Patients With Cancer at Risk for Competing Events SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LOCALIZED PROSTATE-CANCER; BREAST-CANCER; NECK-CANCER; RADICAL PROSTATECTOMY; REGRESSION-MODELS; CLINICAL-TRIALS; ADVANCED HEAD; TUMOR RISK; MORTALITY; COMORBIDITY AB Purpose To compare a novel generalized competing event (GCE) model versus the standard Cox proportional hazards regression model for stratifying elderly patients with cancer who are at risk for competing events. Methods We identified 84,319 patients with nonmetastatic prostate, head and neck, and breast cancers from the SEER-Medicare database. Using demographic, tumor, and clinical characteristics, we trained risk scores on the basis of GCE versus Cox models for cancer-specific mortality and all-cause mortality. In test sets, we examined the predictive ability of the risk scores on the different causes of death, including second cancer mortality, noncancer mortality, and cause-specific mortality, using Fine-Gray regression and area under the curve. We compared how well models stratified subpopulations according to the ratio of the cumulative cause-specific hazard for cancer mortality to the cumulative hazard for overall mortality (omega) using the Akaike Information Criterion. Results In each sample, increasing GCE risk scores were associated with increased cancer-specific mortality and decreased competing mortality, whereas risk scores from Cox models were associated with both increased cancer-specific mortality and competing mortality. GCE models created greater separation in the area under the curve for cancer-specific mortality versus noncancer mortality (P < .001), indicating better discriminatory ability between these events. Comparing the GCE model to Cox models of cause-specific mortality or all-cause mortality, the respective Akaike Information Criterion scores were superior (lower) in each sample: prostate cancer, 28.6 versus 35.5 versus 39.4; head and neck cancer, 21.1 versus 29.4 versus 40.2; and breast cancer, 24.6 versus 32.3 versus 50.8. Conclusion Compared with standard modeling approaches, GCE models improve stratification of elderly patients with cancer according to their risk of dying from cancer relative to overall mortality. (C) 2016 by American Society of Clinical Oncology C1 [Carmona, Ruben; Zakeri, Kaveh; Green, Garrett; Gulaya, Sachin; Xu, Beibei; Verma, Rohan; Williamson, Casey W.; Triplett, Daniel P.; Shen, Hanjie; Murphy, James D.; Mell, Loren K.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Vaida, Florin] Univ Calif San Diego, Med Ctr, 225 Dickinson St, San Diego, CA 92103 USA. [Hwang, Lindsay] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Rose, Brent S.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Rose, Brent S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mell, LK (reprint author), Dept Radiat Med & Appl Sci, 3855 Hlth Sci Dr,MC0843, La Jolla, CA 92093 USA. EM lmell@ucsd.edu FU National Institutes of Health [RR023254] FX Supported by Grant No. RR023254 from the National Institutes of Health. NR 43 TC 3 Z9 3 U1 3 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2016 VL 34 IS 11 BP 1270 EP + DI 10.1200/JCO.2015.65.0739 PG 14 WC Oncology SC Oncology GA DJ6PG UT WOS:000374334800018 PM 26884579 ER PT J AU D'Amico, AV AF D'Amico, Anthony V. TI Query About the Frequency of Biopsy Complications Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.; D'Amico, AV (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 3 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 APR 10 PY 2016 VL 34 IS 11 DI 10.1200/JCO.2015.65.9763 PG 2 WC Oncology SC Oncology GA DJ6PG UT WOS:000374334800024 PM 26884570 ER PT J AU Lonial, S Weiss, BM Usmani, SZ Singhal, S Chari, A Bahlis, NJ Belch, A Krishnan, A Vescio, RA Mateos, MV Mazumder, A Orlowski, RZ Sutherland, HJ Blade, J Scott, EC Oriol, A Berdeja, J Gharibo, M Stevens, DA LeBlanc, R Sebag, M Callander, N Jakubowiak, A White, D de la Rubia, J Richardson, PG Lisby, S Feng, HB Uhlar, CM Khan, I Ahmadi, T Voorhees, PM AF Lonial, Sagar Weiss, Brendan M. Usmani, Saad Z. Singhal, Seema Chari, Ajai Bahlis, Nizar J. Belch, Andrew Krishnan, Amrita Vescio, Robert A. Victoria Mateos, Maria Mazumder, Amitabha Orlowski, Robert Z. Sutherland, Heather J. Blade, Joan Scott, Emma C. Oriol, Albert Berdeja, Jesus Gharibo, Mecide Stevens, Don A. LeBlanc, Richard Sebag, Michael Callander, Natalie Jakubowiak, Andrzej White, Darrell de la Rubia, Javier Richardson, Paul G. Lisby, Steen Feng, Huaibao Uhlar, Clarissa M. Khan, Imran Ahmadi, Tahamtan Voorhees, Peter M. TI Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial SO LANCET LA English DT Article ID ELOTUZUMAB; MULTICENTER; SURVIVAL; THERAPY; RISK AB Background New treatment options are needed for patients with multiple myeloma that is refractory to proteasome inhibitors and immunomodulatory drugs. We assessed daratumumab, a novel CD38-targeted monoclonal antibody, in patients with refractory multiple myeloma. Methods In this open-label, multicentre, phase 2 trial done in Canada, Spain, and the USA, patients (age >= 18 years) with multiple myeloma who were previously treated with at least three lines of therapy (including proteasome inhibitors and immunomodulatory drugs), or were refractory to both proteasome inhibitors and immunomodulatory drugs, were randomly allocated in a 1:1 ratio to receive intravenous daratumumab 8 mg/kg or 16 mg/kg in part 1 stage 1 of the study, to decide the dose for further assessment in part 2. Patients received 8 mg/kg every 4 weeks, or 16 mg/kg per week for 8 weeks (cycles 1 and 2), then every 2 weeks for 16 weeks (cycles 3-6), and then every 4 weeks thereafter (cycle 7 and higher). The allocation schedule was computer-generated and randomisation, with permuted blocks, was done centrally with an interactive web response system. In part 1 stage 2 and part 2, patients received 16 mg/kg dosed as in part 1 stage 1. The primary endpoint was overall response rate (partial response [PR] + very good PR + complete response [CR] + stringent CR). All patients who received at least one dose of daratumumab were included in the analysis. The trial is registered with ClinicalTrials.gov, number NCT01985126. Findings The study is ongoing. In part 1 stage 1 of the study, 18 patients were randomly allocated to the 8 mg/kg group and 16 to the 16 mg/kg group. Findings are reported for the 106 patients who received daratumumab 16 mg/kg in parts 1 and 2. Patients received a median of five previous lines of therapy (range 2-14). 85 (80%) patients had previously received autologous stem cell transplantation, 101 (95%) were refractory to the most recent proteasome inhibitors and immunomodulatory drugs used, and 103 (97%) were refractory to the last line of therapy. Overall responses were noted in 31 patients (29.2%, 95% CI 20.8-38.9)-three (2.8%, 0.6-8.0) had a stringent CR, ten (9.4%, 4.6-16.7) had a very good PR, and 18 (17.0%, 10.4-25.5) had a PR. The median time to first response was 1.0 month (range 0.9-5.6). Median duration of response was 7.4 months (95% CI 5.5-not estimable) and progression-free survival was 3.7 months (95% CI 2.8-4.6). The 12-month overall survival was 64.8% (95% CI 51.2-75.5) and, at a subsequent cutoff, median overall survival was 17.5 months (95% CI 13.7-not estimable). Daratumumab was well tolerated; fatigue (42 [40%] patients) and anaemia (35 [33%]) of any grade were the most common adverse events. No drug-related adverse events led to treatment discontinuation. Interpretation Daratumumab monotherapy showed encouraging efficacy in heavily pretreated and refractory patients with multiple myeloma, with a favourable safety profile in this population of patients. C1 [Lonial, Sagar] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, 201 Dowman Dr, Atlanta, GA 30322 USA. [Weiss, Brendan M.] Univ Penn, Abramson Canc Ctr, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Weiss, Brendan M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Usmani, Saad Z.] Carolinas Healthcare Syst, Levine Canc Inst, Charlotte, NC USA. [Singhal, Seema] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL 60611 USA. [Chari, Ajai] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Bahlis, Nizar J.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. [Belch, Andrew] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Krishnan, Amrita] City Hope Natl Med Ctr, Judy & Bernard Briskin Myeloma Ctr, Duarte, CA USA. [Vescio, Robert A.] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Victoria Mateos, Maria] Univ Hosp Salamanca, Inst Invest Biomed Salamanca, Salamanca, Spain. [Mazumder, Amitabha] NYU Langone Med Ctr, Perlmutter Canc Ctr, New York, NY USA. [Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. [Sutherland, Heather J.] Univ British Columbia, Leukemia Bone Marrow Transplant Program, Vancouver, BC V5Z 1M9, Canada. [Blade, Joan] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain. [Scott, Emma C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Oriol, Albert] Hosp Badalona Germans Trias & Pujol, Inst Josep Carreras, Inst Catala Oncol, Barcelona, Spain. [Berdeja, Jesus] Sarah Cannon Res Inst, Nashville, TN USA. [Gharibo, Mecide] Rutgers State Univ, Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Stevens, Don A.] Norton Hlth Care, Louisville, KY USA. [LeBlanc, Richard] Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. [Sebag, Michael] Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. [Callander, Natalie] Univ Wisconsin, Sch Med, Madison, WI USA. [Jakubowiak, Andrzej] Univ Chicago Med, Chicago, IL USA. [White, Darrell] Dalhousie Univ, Halifax, NS, Canada. [White, Darrell] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [de la Rubia, Javier] Hosp Dr Peset, Valencia, Spain. [de la Rubia, Javier] Univ Catolica San Vicente Martir, Valencia, Spain. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Lisby, Steen] Genmab, Copenhagen, Denmark. [Feng, Huaibao; Khan, Imran] Janssen Res & Dev, Raritan, NJ USA. [Uhlar, Clarissa M.; Ahmadi, Tahamtan] Janssen Res & Dev, Spring House, PA USA. [Voorhees, Peter M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Div Hematol & Oncol, Chapel Hill, NC 27599 USA. RP Lonial, S (reprint author), Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, 201 Dowman Dr, Atlanta, GA 30322 USA. EM sloni01@emory.edu FU Janssen Research Development FX Janssen Research & Development. NR 25 TC 74 Z9 75 U1 7 U2 11 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 APR 9 PY 2016 VL 387 IS 10027 BP 1551 EP 1560 DI 10.1016/S0140-6736(15)01120-4 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DI8HH UT WOS:000373741600031 PM 26778538 ER PT J AU Atochin, DN Schepetkin, IA Khlebnikov, AI Seledtsov, VI Swanson, H Quinn, MT Huang, PL AF Atochin, Dmitriy N. Schepetkin, Igor A. Khlebnikov, Andrei I. Seledtsov, Victor I. Swanson, Helen Quinn, Mark T. Huang, Paul L. TI A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia-reperfusion injury in mice SO NEUROSCIENCE LETTERS LA English DT Article DE c-Jun N-terminal kinase; Cerebral reperfusion; Nitric oxide ID NITRIC-OXIDE SYNTHASE; BRAIN ISCHEMIA/REPERFUSION; MATRIX METALLOPROTEINASES; ENDOTHELIAL-CELLS; SIGNALING PATHWAY; S-NITROSYLATION; NEURONAL DEATH; JNK; CONTRIBUTES; STROKE AB The c-Jun N-terminal kinase (JNK) has been shown to be an important regulator of neuronal cell death. Previously, we synthesized the sodium salt of 11H-indeno[1,2-b]quinoxalin-11-one (IQ-1S) and demonstrated that it was a high-affinity inhibitor of the JNK family. In the present work, we found that IQ-1S could release nitric oxide (NO) during its enzymatic metabolism by liver microsomes. Moreover, serum nitrite/nitrate concentration in mice increased after intraperitoneal injection of IQ-1S. Because of these dual actions as INK inhibitor and NO-donor, the therapeutic potential of IQ-1S was evaluated in an animal stroke model. We subjected wild-type C57BL6 mice to focal ischemia (30 min) with subsequent reperfusion (48 h). Mice were treated with IQ-1S (25 mg/kg) suspended in 10% solutol or with vehicle alone 30 min before and 24 h after middle cerebral artery (MCA) occlusion (MCAO). Using laser-Doppler flowmetry, we monitored cerebral blood flow (CBF) above the MCA during 30 min of MCAO provoked by a filament and during the first 30 min of subsequent reperfusion. In mice treated with IQ-1S, ischemic and reperfusion values of CBF were not different from vehicle-treated mice. However, IQ-1S treated mice demonstrated markedly reduced neurological deficit and infarct volumes as compared with vehicle-treated mice after 48 h of reperfusion. Our results indicate that the novel JNK inhibitor releases NO during its oxidoreductive bioconversion and improves stroke outcome in a mouse model of cerebral reperfusion. We conclude that IQ-1S is a promising dual functional agent for the treatment of cerebral ischemia and reperfusion injury. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Atochin, Dmitriy N.; Swanson, Helen; Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, 149 East 13th St, Charlestown, MA 02129 USA. [Atochin, Dmitriy N.; Schepetkin, Igor A.] Tomsk Polytech Univ, RASA Ctr Tomsk, Tomsk 634050, Russia. [Schepetkin, Igor A.; Quinn, Mark T.] Montana State Univ, Dept Microbiol & Immunol, Bozeman, MT 59715 USA. [Khlebnikov, Andrei I.] Tomsk Polytech Univ, Dept Biotechnol & Organ Chem, Tomsk 634050, Russia. [Khlebnikov, Andrei I.] Altai State Tech Univ, Dept Chem, Barnaul 656038, Russia. [Seledtsov, Victor I.] Immanuel Kant Balt Fed Univ, Kaliningrad 236041, Russia. RP Atochin, DN (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, 149 East 13th St, Charlestown, MA 02129 USA.; Atochin, DN (reprint author), Tomsk Polytech Univ, RASA Ctr Tomsk, Tomsk 634050, Russia. EM atochin@cvrc.mgh.harvard.edu RI Khlebnikov, Andrei/L-9545-2014; Atochin, Dmitriy/Q-3150-2016 OI Khlebnikov, Andrei/0000-0002-3022-4510; FU American Heart Association [13GRNT16930060]; NIH IDeA Program Grant [GM110732]; M.J. Murdock Charitable Trust; United States Department of Agriculture National Institute of Food and Agriculture Hatch project; Montana State University Agricultural Experiment Station FX This work was supported in part by American Heart Association Grant-in-Aid (13GRNT16930060), NIH IDeA Program Grant GM110732 (M.T.Q.), an equipment grant from the M.J. Murdock Charitable Trust, a United States Department of Agriculture National Institute of Food and Agriculture Hatch project, and the Montana State University Agricultural Experiment Station. NR 45 TC 1 Z9 2 U1 6 U2 10 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 APR 8 PY 2016 VL 618 BP 45 EP 49 DI 10.1016/j.neulet.2016.02.033 PG 5 WC Neurosciences SC Neurosciences & Neurology GA DK0NS UT WOS:000374610100008 PM 26923672 ER PT J AU Coronado-Montoya, S Levis, AW Kwakkenbos, L Steele, RJ Turner, EH Thombs, BD AF Coronado-Montoya, Stephanie Levis, Alexander W. Kwakkenbos, Linda Steele, Russell J. Turner, Erick H. Thombs, Brett D. TI Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions SO PLOS ONE LA English DT Article ID QUALITY-OF-LIFE; COGNITIVE THERAPY; STRESS REDUCTION; PUBLICATION BIAS; EXCESS SIGNIFICANCE; PRIMARY OUTCOMES; METAANALYSIS; DEPRESSION; ANXIETY; PREVENTION AB Background A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of "positive" results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified. Methods CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses. Results 108 (87%) of 124 published trials reported >= 1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases. Conclusions The proportion of mindfulnessbased therapy trials with statistically significant results may overstate what would occur in practice. C1 [Coronado-Montoya, Stephanie; Levis, Alexander W.; Kwakkenbos, Linda; Steele, Russell J.; Thombs, Brett D.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. [Coronado-Montoya, Stephanie; Kwakkenbos, Linda; Thombs, Brett D.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Steele, Russell J.; Thombs, Brett D.] McGill Univ, Dept Math & Stat, Montreal, PQ, Canada. [Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Turner, Erick H.] Portland VA Med Ctr, Dept Psychiat, Portland, OR USA. [Thombs, Brett D.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. [Thombs, Brett D.] McGill Univ, Dept Med, Montreal, PQ, Canada. [Thombs, Brett D.] McGill Univ, Dept Educ & Counselling Psychol, Montreal, PQ, Canada. [Thombs, Brett D.] McGill Univ, Dept Psychol, Montreal, PQ, Canada. [Thombs, Brett D.] McGill Univ, Sch Nursing, Montreal, PQ, Canada. RP Thombs, BD (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.; Thombs, BD (reprint author), McGill Univ, Dept Psychiat, Montreal, PQ, Canada.; Thombs, BD (reprint author), McGill Univ, Dept Math & Stat, Montreal, PQ, Canada.; Thombs, BD (reprint author), McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.; Thombs, BD (reprint author), McGill Univ, Dept Med, Montreal, PQ, Canada.; Thombs, BD (reprint author), McGill Univ, Dept Educ & Counselling Psychol, Montreal, PQ, Canada.; Thombs, BD (reprint author), McGill Univ, Dept Psychol, Montreal, PQ, Canada.; Thombs, BD (reprint author), McGill Univ, Sch Nursing, Montreal, PQ, Canada. EM brett.thombs@mcgill.ca NR 71 TC 1 Z9 1 U1 6 U2 24 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 APR 8 PY 2016 VL 11 IS 4 AR e0153220 DI 10.1371/journal.pone.0153220 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI6JK UT WOS:000373604800022 PM 27058355 ER PT J AU Tirosh, I Izar, B Prakadan, SM Wadsworth, MH Treacy, D Trombetta, JJ Rotem, A Rodman, C Lian, C Murphy, G Fallahi-Sichani, M Dutton-Regester, K Lin, JR Cohen, O Shah, P Lu, D Genshaft, AS Hughes, TK Ziegler, CGK Kazer, SW Gaillard, A Kolb, KE Villani, AC Johannessen, CM Andreev, AY Van Allen, EM Bertagnolli, M Sorger, PK Sullivan, RJ Flaherty, KT Frederick, DT Jane-Valbuena, J Yoon, CH Rozenblatt-Rosen, O Shalek, AK Regev, A Garraway, LA AF Tirosh, Itay Izar, Benjamin Prakadan, Sanjay M. Wadsworth, Marc H., II Treacy, Daniel Trombetta, John J. Rotem, Asaf Rodman, Christopher Lian, Christine Murphy, George Fallahi-Sichani, Mohammad Dutton-Regester, Ken Lin, Jia-Ren Cohen, Ofir Shah, Parin Lu, Diana Genshaft, Alex S. Hughes, Travis K. Ziegler, Carly G. K. Kazer, Samuel W. Gaillard, Aleth Kolb, Kellie E. Villani, Alexandra-Chloe Johannessen, Cory M. Andreev, Aleksandr Y. Van Allen, Eliezer M. Bertagnolli, Monica Sorger, Peter K. Sullivan, Ryan J. Flaherty, Keith T. Frederick, Dennie T. Jane-Valbuena, Judit Yoon, Charles H. Rozenblatt-Rosen, Orit Shalek, Alex K. Regev, Aviv Garraway, Levi A. TI Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq SO SCIENCE LA English DT Article ID CD8(+) T-CELLS; LUNG-CANCER; CTLA-4 BLOCKADE; AXL KINASE; RESISTANCE; SAFETY; INHIBITION; EXHAUSTION; NIVOLUMAB; SENSITIVITY AB To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase. Single-cell analyses suggested distinct tumor microenvironmental patterns, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single-cell genomics offers insights with implications for both targeted and immune therapies. C1 [Tirosh, Itay; Izar, Benjamin; Prakadan, Sanjay M.; Wadsworth, Marc H., II; Treacy, Daniel; Trombetta, John J.; Rotem, Asaf; Rodman, Christopher; Dutton-Regester, Ken; Cohen, Ofir; Lu, Diana; Genshaft, Alex S.; Hughes, Travis K.; Ziegler, Carly G. K.; Kazer, Samuel W.; Gaillard, Aleth; Kolb, Kellie E.; Villani, Alexandra-Chloe; Johannessen, Cory M.; Andreev, Aleksandr Y.; Van Allen, Eliezer M.; Jane-Valbuena, Judit; Rozenblatt-Rosen, Orit; Shalek, Alex K.; Regev, Aviv; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Izar, Benjamin; Rotem, Asaf; Dutton-Regester, Ken; Shah, Parin; Van Allen, Eliezer M.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Izar, Benjamin; Rotem, Asaf; Van Allen, Eliezer M.; Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02215 USA. [Prakadan, Sanjay M.; Wadsworth, Marc H., II; Genshaft, Alex S.; Hughes, Travis K.; Ziegler, Carly G. K.; Kazer, Samuel W.; Gaillard, Aleth; Kolb, Kellie E.; Shalek, Alex K.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Prakadan, Sanjay M.; Wadsworth, Marc H., II; Genshaft, Alex S.; Kazer, Samuel W.; Gaillard, Aleth; Kolb, Kellie E.; Shalek, Alex K.] MIT, Dept Chem, Cambridge, MA 02142 USA. [Prakadan, Sanjay M.; Wadsworth, Marc H., II; Genshaft, Alex S.; Hughes, Travis K.; Ziegler, Carly G. K.; Kazer, Samuel W.; Gaillard, Aleth; Kolb, Kellie E.; Shalek, Alex K.] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Prakadan, Sanjay M.; Wadsworth, Marc H., II; Genshaft, Alex S.; Hughes, Travis K.; Ziegler, Carly G. K.; Kazer, Samuel W.; Gaillard, Aleth; Kolb, Kellie E.; Shalek, Alex K.] Harvard Univ, Cambridge, MA 02139 USA. [Lian, Christine; Murphy, George] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Fallahi-Sichani, Mohammad; Sorger, Peter K.] Harvard Univ, Sch Med, Dept Syst Biol, Program Therapeut Sci, Boston, MA 02115 USA. [Dutton-Regester, Ken] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia. [Lin, Jia-Ren; Sorger, Peter K.] Harvard Univ, Sch Med, HMS LINCS Ctr & Lab Syst Pharmacol, Boston, MA 02115 USA. [Hughes, Travis K.; Ziegler, Carly G. K.; Shalek, Alex K.] Harvard Univ, Sch Med, Div Hlth Sci & Technol, Boston, MA 02115 USA. [Bertagnolli, Monica; Yoon, Charles H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg Oncol, Boston, MA 02215 USA. [Bertagnolli, Monica; Yoon, Charles H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg Oncol, Boston, MA 02215 USA. [Sorger, Peter K.; Garraway, Levi A.] Harvard Univ, Ludwig Ctr, Boston, MA 02215 USA. [Sullivan, Ryan J.; Flaherty, Keith T.; Frederick, Dennie T.] Massachusetts Gen Hosp, Ctr Canc, Div Med Oncol, Boston, MA 02114 USA. [Shalek, Alex K.] Massachusetts Gen Hosp, Dept Immunol, Boston, MA 02114 USA. [Regev, Aviv] MIT, Dept Biol, Boston, MA 02142 USA. [Regev, Aviv] MIT, Koch Inst, Boston, MA 02142 USA. [Regev, Aviv] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Izar, B; Regev, A; Garraway, LA (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Izar, B; Garraway, LA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Izar, B; Garraway, LA (reprint author), Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02215 USA.; Garraway, LA (reprint author), Harvard Univ, Ludwig Ctr, Boston, MA 02215 USA.; Regev, A (reprint author), MIT, Dept Biol, Boston, MA 02142 USA.; Regev, A (reprint author), MIT, Koch Inst, Boston, MA 02142 USA.; Regev, A (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. EM bizar@partners.org; aregev@broadinstitute.org; levi_garraway@dfci.harvard.edu FU National Cancer Institute (NCI) [P01CA163222, R35CA197737]; Dr. Miriam and Sheldon Adelson Medical Research Foundation; Melanoma Research Alliance; Ludwig Center at Harvard Medical School; Howard Hughes Medicine Institute; Klarman Cell Observatory; STARR Cancer Consortium; NCI [1U24CA180922, K99CA194163]; Koch Institute from NCI [P30-CA14051]; Broad Institute; Searle Scholars Program; Beckman Young Investigator Program; NIH [DP2 OD020839, P50GM107618]; Wong Family Award for Translational Oncology of the Dana-Farber Cancer Institute; Human Frontier Science Program long-term fellowship, a Rothschild fellowship; Integrative Cancer Biology Program grant [U54CA112962]; Next Generation Fund at the Broad Institute of MIT and Harvard; NSF Graduate Research Fellowships Program; Ludwig Center at Harvard FX We thank M. Singer, A. Anderson, V. K. Kuchroo, and A. Aguirre for fruitful discussions; S. Barthel and T. Schatton for providing the Tim-3 antibody; Q. Zhan for preparing IF staining; and J. Thurman for guidance on complement biology. L.A.G., B.I., S.M.P., A. Re., O.R.-R., A. K. S., I. T., M.H.W.II, The Broad Institute, Brigham and Women's Hospital, Dana-Farber Cancer Institute, MIT, and the president and fellows of Harvard College have filed a patent application (BI-2015/077) that relates to tumor and microenvironment gene expression, compositions of matter, and methods of use thereof. L.A.G., B.I., A.Ro., and the Dana-Farber Cancer Institute have filed a patent application (DFCI 2105.001) that relates to cancer-patient-derived tumor dissociation for biological analysis. L.A.G was supported by National Cancer Institute (NCI) grants P01CA163222 and R35CA197737, the Dr. Miriam and Sheldon Adelson Medical Research Foundation, the Melanoma Research Alliance, and the Ludwig Center at Harvard Medical School. L.A.G. is a member of the scientific advisory board for Warp Drive; a consultant for Novartis, Bayer Oncology, and Foundation Medicine, and an equity holder in Foundation Medicine. A. Re. was supported by funds from the Howard Hughes Medicine Institute, the Klarman Cell Observatory, STARR Cancer Consortium, NCI grant 1U24CA180922, Koch Institute support (core) grant P30-CA14051 from NCI, and the Broad Institute. A. Re. is a scientific advisory board member for ThermoFisher Scientific and Syros Pharmaceuticals and a consultant for Driver Group. E.M.V.A. is a consultant for Roche Ventana, Takeda, and Third Rock Ventures. A. K. S. was supported by the Searle Scholars Program, the Beckman Young Investigator Program, and the NIH New Innovator Award (DP2 OD020839). B.I. was supported by the Wong Family Award for Translational Oncology of the Dana-Farber Cancer Institute. I. T. was supported by a Human Frontier Science Program long-term fellowship, a Rothschild fellowship, STARR Cancer Consortium, and an Integrative Cancer Biology Program grant (U54CA112962). I. T., A. K. S., and O.R.-R. were supported by the Broad Institute. O. R.-R. was supported by a grant from the Next Generation Fund at the Broad Institute of MIT and Harvard. S.W.K. was supported by a fellowship from the NSF Graduate Research Fellowships Program. M.F.-S. was supported by the NCI (grant K99CA194163), and P.K.S. was supported by the NIH (grant P50GM107618) and the Ludwig Center at Harvard. Processed single-cell and bulk RNA-seq data are available through the Gene Expression Omnibus (accession numbers GSE72056 and GSE77940). Raw RNA-seq and WES data will be available through dbGAP (the database of Genotypes and Phenotypes). NR 49 TC 52 Z9 53 U1 27 U2 57 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 APR 8 PY 2016 VL 352 IS 6282 BP 189 EP 196 DI 10.1126/science.aad0501 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI7LM UT WOS:000373681600038 PM 27124452 ER PT J AU Titov, DV Cracan, V Goodman, RP Peng, J Grabarek, Z Mootha, VK AF Titov, Denis V. Cracan, Valentin Goodman, Russell P. Peng, Jun Grabarek, Zenon Mootha, Vamsi K. TI Complementation of mitochondrial electron transport chain by manipulation of the NAD(+)/NADH ratio SO SCIENCE LA English DT Article ID NICOTINAMIDE-ADENINE-DINUCLEOTIDE; SUPPORTING ASPARTATE BIOSYNTHESIS; NADH-OXIDASE; SACCHAROMYCES-CEREVISIAE; LACTOBACILLUS-BREVIS; OVERFLOW METABOLISM; CELL-PROLIFERATION; REDOX STATE; PYRUVATE; CHLORAMPHENICOL AB A decline in electron transport chain (ETC) activity is associated with many human diseases. Although diminished mitochondrial adenosine triphosphate production is recognized as a source of pathology, the contribution of the associated reduction in the ratio of the amount of oxidized nicotinamide adenine dinucleotide (NAD(+)) to that of its reduced form (NADH) is less clear. We used a water-forming NADH oxidase from Lactobacillus brevis (LbNOX) as a genetic tool for inducing a compartment-specific increase of the NAD(+)/NADH ratio in human cells. We used LbNOX to demonstrate the dependence of key metabolic fluxes, gluconeogenesis, and signaling on the cytosolic or mitochondrial NAD(+)/NADH ratios. Expression of LbNOX in the cytosol or mitochondria ameliorated proliferative and metabolic defects caused by an impaired ETC. The results underscore the role of reductive stress in mitochondrial pathogenesis and demonstrate the utility of targeted LbNOX for direct, compartment-specific manipulation of redox state. C1 [Titov, Denis V.; Cracan, Valentin; Goodman, Russell P.; Peng, Jun; Grabarek, Zenon; Mootha, Vamsi K.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Titov, Denis V.; Cracan, Valentin; Goodman, Russell P.; Peng, Jun; Grabarek, Zenon; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Titov, Denis V.; Cracan, Valentin; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Titov, Denis V.; Cracan, Valentin; Grabarek, Zenon; Mootha, Vamsi K.] Broad Inst, Cambridge, MA USA. [Goodman, Russell P.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Mootha, VK (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA.; Mootha, VK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Mootha, VK (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.; Mootha, VK (reprint author), Broad Inst, Cambridge, MA USA. EM vamsi@hms.harvard.edu OI Titov, Denis/0000-0001-5677-0651 FU NIH [T-R01 R01GM099683, T32DK007191]; Tosteson; Fund for Medical Discovery Postdoctoral Fellowship Award FX We thank V. Vitvitsky for technical support with HPLC. We thank members of the Mootha lab for valuable discussions and feedback. This work was supported by a T-R01 R01GM099683 grant from NIH. D.V.T. was supported by a Tosteson and Fund for Medical Discovery Postdoctoral Fellowship Award. R.P.G. was supported by a T32DK007191 grant from NIH. V.K.M. is an investigator of the Howard Hughes Medical Institute. The Massachusetts General Hospital has filed a patent application on the technology described in this paper. Atomic coordinates and structure factors have been deposited in the Protein Data Bank with accession number 5ER0. NR 34 TC 6 Z9 6 U1 14 U2 46 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 APR 8 PY 2016 VL 352 IS 6282 BP 231 EP 235 DI 10.1126/science.aad4017 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI7LM UT WOS:000373681600048 PM 27124460 ER PT J AU Pucci, F Garris, C Lai, CP Newton, A Pfirschke, C Engblom, C Alvarez, D Sprachman, M Evavold, C Magnuson, A von Andrian, UH Glatz, K Breakefield, XO Mempel, TR Weissleder, R Pittet, MJ AF Pucci, Ferdinando Garris, Christopher Lai, Charles P. Newton, Andita Pfirschke, Christina Engblom, Camilla Alvarez, David Sprachman, Melissa Evavold, Charles Magnuson, Angela von Andrian, Ulrich H. Glatz, Katharina Breakefield, Xandra O. Mempel, Thorsten R. Weissleder, Ralph Pittet, Mikael J. TI SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions SO SCIENCE LA English DT Article ID SUBCAPSULAR SINUS MACROPHAGES; LYMPH-NODES; IN-VIVO; EXTRACELLULAR VESICLES; CANCER; INFLAMMATION; INFECTION; EXOSOMES; MICROVESICLES; GLIOBLASTOMA AB Tumor-derived extracellular vesicles (tEVs) are important signals in tumor-host cell communication, yet it remains unclear how endogenously produced tEVs affect the host in different areas of the body. We combined imaging and genetic analysis to track melanoma-derived vesicles at organismal, cellular, and molecular scales to show that endogenous tEVs efficiently disseminate via lymphatics and preferentially bind subcapsular sinus (SCS) CD169(+) macrophages in tumor-draining lymph nodes (tdLNs) in mice and humans. The CD169(+) macrophage layer physically blocks tEVdissemination but is undermined during tumor progression and by therapeutic agents. A disrupted SCS macrophage barrier enables tEVs to enter the lymph node cortex, interact with B cells, and foster tumor-promoting humoral immunity. Thus, CD169(+) macrophages may act as tumor suppressors by containing tEV spread and ensuing cancer-enhancing immunity. C1 [Pucci, Ferdinando; Garris, Christopher; Newton, Andita; Pfirschke, Christina; Engblom, Camilla; Sprachman, Melissa; Evavold, Charles; Magnuson, Angela; Weissleder, Ralph; Pittet, Mikael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Res Inst, Boston, MA 02114 USA. [Garris, Christopher; Engblom, Camilla; Evavold, Charles] Harvard Univ, Sch Med, Grad Program Immunol, Boston, MA 02115 USA. [Lai, Charles P.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Res Inst, Charlestown, MA 02129 USA. [Alvarez, David; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Glatz, Katharina] Univ Basel Hosp, Inst Pathol, CH-4031 Basel, Switzerland. [Mempel, Thorsten R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Res Inst, Charlestown, MA 02129 USA. [Pucci, Ferdinando] Torque Therapeut Inc, Cambridge, MA 02142 USA. [Lai, Charles P.] Natl Tsing Hua Univ, Inst Biomed Engn, Hsinchu, Taiwan. RP Pittet, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Res Inst, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu RI Lai, Charles/D-5442-2017 FU Samana Cay MGH Research Scholar Fund; NIH [R21-CA190344, P50-CA86355, R01-AI084880, U54-CA126515, T32CA79443, RO1EB010011, 1R01CA164448, 1R33CA202064, P01-CA069246, U19 CA179563, R01 AI097052, F31-CA196035]; EMBO long-term fellowship; MGH ECOR Funds for Medical Discovery Fellowship; Deutsche Forschungsgemeinschaft [PF809/1-1]; Canadian Institutes of Health Research; Boehringer Ingelheim FX We thank M. Ericsson for helping with electron microscopy studies, T. Murooka for multiphoton microscopy experiments, and S. Mordecai for imaging flow cytometry. The data presented in this manuscript are tabulated in the main paper and in the supplementary materials. Supported by the Samana Cay MGH Research Scholar Fund and NIH grants R21-CA190344, P50-CA86355, and R01-AI084880 (M.J.P.); NIH grants U54-CA126515, T32CA79443, RO1EB010011, 1R01CA164448, and 1R33CA202064 (R.W.); NIH grant P01-CA069246 (X.O.B. and R.W.); NIH grant U19 CA179563 (X.O.B. and T.R.M.); NIH grant R01 AI097052 (T.R.M.); NIH grant F31-CA196035 (C.G.); an EMBO long-term fellowship and an MGH ECOR Funds for Medical Discovery Fellowship (F.P.); Deutsche Forschungsgemeinschaft grant PF809/1-1 (C.P.); a Canadian Institutes of Health Research postdoctoral fellowship (C.P.L.); and Boehringer Ingelheim Funds (C.E.). NR 29 TC 14 Z9 14 U1 10 U2 24 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 APR 8 PY 2016 VL 352 IS 6282 BP 242 EP 246 DI 10.1126/science.aaf1328 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI7LM UT WOS:000373681600051 PM 26989197 ER PT J AU Kozlenkov, A Wang, MH Roussos, P Rudchenko, S Barbu, M Bibikova, M Klotzle, B Dwork, AJ Zhang, B Hurd, YL Koonin, EV Wegner, M Dracheva, S AF Kozlenkov, Alexey Wang, Minghui Roussos, Panos Rudchenko, Sergei Barbu, Mihaela Bibikova, Marina Klotzle, Brandy Dwork, Andrew J. Zhang, Bin Hurd, Yasmin L. Koonin, Eugene V. Wegner, Michael Dracheva, Stella TI Substantial DNA methylation differences between two major neuronal subtypes in human brain SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EMBRYONIC STEM-CELLS; HUMAN HOUSEKEEPING GENES; RETT-SYNDROME; GABAERGIC INTERNEURONS; EPIGENETIC MEMORY; PREFRONTAL CORTEX; SITE RESOLUTION; MECP2 BINDS; RNA-SEQ; SCHIZOPHRENIA AB The brain is built from a large number of cell types which have been historically classified using location, morphology and molecular markers. Recent research suggests an important role of epigenetics in shaping and maintaining cell identity in the brain. To elucidate the role of DNA methylation in neuronal differentiation, we developed a new protocol for separation of nuclei from the two major populations of human prefrontal cortex neurons-GABAergic interneurons and glutamatergic (GLU) projection neurons. Major differences between the neuronal subtypes were revealed in CpG, non-CpG and hydroxymethylation (hCpG). A dramatically greater number of undermethylated CpG sites in GLU versus GABA neurons were identified. These differences did not directly translate into differences in gene expression and did not stem from the differences in hCpG methylation, as more hCpG methylation was detected in GLU versus GABA neurons. Notably, a comparable number of undermethylated non-CpG sites were identified in GLU and GABA neurons, and non-CpG methylation was a better predictor of subtype-specific gene expression compared to CpG methylation. Regions that are differentially methylated in GABA and GLU neurons were significantly enriched for schizophrenia risk loci. Collectively, our findings suggest that functional differences between neuronal subtypes are linked to their epigenetic specification. C1 [Kozlenkov, Alexey; Roussos, Panos; Dracheva, Stella] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Kozlenkov, Alexey; Roussos, Panos; Hurd, Yasmin L.; Dracheva, Stella] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Kozlenkov, Alexey; Roussos, Panos; Hurd, Yasmin L.; Dracheva, Stella] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Wang, Minghui; Roussos, Panos; Zhang, Bin] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Rudchenko, Sergei; Barbu, Mihaela] Hosp Special Surg, New York, NY 10021 USA. [Bibikova, Marina; Klotzle, Brandy] Illumina Inc, San Diego, CA 92122 USA. [Dwork, Andrew J.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Wegner, Michael] Univ Erlangen Nurnberg, Emil Fischer Zentrum, Inst Biochem, D-91054 Erlangen, Germany. RP Dracheva, S (reprint author), James J Peters VA Med Ctr, Bronx, NY 10468 USA.; Dracheva, S (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.; Dracheva, S (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM Stella.Dracheva@mssm.edu RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 FU National Institute of Mental Health [R21MH103877]; U.S. Department of Veterans Affairs [BX001829]; U.S. Department of Health and Human Services; National Institute of Health FX National Institute of Mental Health [R21MH103877 that is a part of the PsychENCODE consortium to S.D.]; U.S. Department of Veterans Affairs [Merit Review Award BX001829 to S.D.]; Intramural funds of the U.S. Department of Health and Human Services to National Library of Medicine (to E.V.K.). Funding for open access charge: National Institute of Health. NR 96 TC 7 Z9 7 U1 5 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 7 PY 2016 VL 44 IS 6 BP 2593 EP 2612 DI 10.1093/nar/gkv1304 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DJ9YW UT WOS:000374570500020 PM 26612861 ER PT J AU Puram, RV Kowalczyk, MS de Boer, CG Schneider, RK Miller, PG McConkey, M Tothova, Z Tejero, H Heckl, D Jaras, M Chen, MC Li, HB Tamayo, A Cowley, GS Rozenblatt-Rosen, O Al-Shahrour, F Regev, A Ebert, BL AF Puram, Rishi V. Kowalczyk, Monika S. de Boer, Carl G. Schneider, Rebekka K. Miller, Peter G. McConkey, Marie Tothova, Zuzana Tejero, Hector Heckl, Dirk Jaras, Marcus Chen, Michelle C. Li, Hubo Tamayo, Alfred Cowley, Glenn S. Rozenblatt-Rosen, Orit Al-Shahrour, Fatima Regev, Aviv Ebert, Benjamin L. TI Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML SO CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM; BONE-MARROW; IN-VIVO; THERAPEUTIC OPPORTUNITIES; COMMITTED PROGENITOR; PROTEIN BMAL1; MICE; EXPRESSION; COMPONENT AB Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNAi screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically and phenotypically defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemiaspecific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML. C1 [Puram, Rishi V.; Schneider, Rebekka K.; Miller, Peter G.; McConkey, Marie; Tothova, Zuzana; Heckl, Dirk; Jaras, Marcus; Chen, Michelle C.; Al-Shahrour, Fatima; Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. [Puram, Rishi V.; Li, Hubo] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. [Puram, Rishi V.; Kowalczyk, Monika S.; de Boer, Carl G.; Tothova, Zuzana; Cowley, Glenn S.; Rozenblatt-Rosen, Orit; Regev, Aviv; Ebert, Benjamin L.] Broad Inst Harvard Univ & MIT, Cambridge, MA 02142 USA. [Miller, Peter G.; Tothova, Zuzana; Li, Hubo; Ebert, Benjamin L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Tejero, Hector; Al-Shahrour, Fatima] Spanish Natl Canc Res Ctr CNIO, Translat Bioinformat Unit, Madrid 28029, Spain. [Heckl, Dirk] Hannover Med Sch, Dept Pediat Hematol & Oncol, D-30625 Hannover, NH, Germany. [Jaras, Marcus] Lund Univ, Dept Clin Genet, S-22184 Lund, Sweden. [Tamayo, Alfred] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Regev, Aviv] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Regev, Aviv] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Ebert, BL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA.; Ebert, BL (reprint author), Broad Inst Harvard Univ & MIT, Cambridge, MA 02142 USA.; Ebert, BL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bebert@partners.org OI Tamayo, Alfred/0000-0002-2321-0831 FU Harvard Stem Cell Institute; NIH [P01 CA066996, R01 HL082945]; Klarman Family Foundation; Koch Institute Core Grant from National Cancer Institute [P30-CA14051]; Mildred-Scheel fellowship from German Cancer Foundation; Medical Scientist Training Program from National Institute of General Medical Sciences [T32GM007753] FX The authors would like to thank Charles Weitz, Scott Armstrong, George Daley, Itay Tirosh, R. Grant Rowe, and Samantha Morris for helpful scientific discussions. The germline Per2 mutant and Bmal1 knockout mice were generous gifts from Tyler Jacks and Thales Papagiannakopoulos. This work was funded by the Harvard Stem Cell Institute, the NIH (P01 CA066996 and R01 HL082945), the Klarman Family Foundation, and the Koch Institute Core Grant from the National Cancer Institute (P30-CA14051). D.H. was supported by a Mildred-Scheel fellowship from the German Cancer Foundation. R.V.P. was funded by the Medical Scientist Training Program grant T32GM007753 from the National Institute of General Medical Sciences. NR 76 TC 8 Z9 8 U1 11 U2 27 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 APR 7 PY 2016 VL 165 IS 2 BP 303 EP 316 DI 10.1016/j.cell.2016.03.015 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DJ3RJ UT WOS:000374123000010 PM 27058663 ER PT J AU Pogue, BW Elliott, JT Kanick, SC Davis, SC Samkoe, KS Maytin, EV Pereira, SP Hasan, T AF Pogue, Brian W. Elliott, Jonathan T. Kanick, Stephen C. Davis, Scott C. Samkoe, Kimberley S. Maytin, Edward V. Pereira, Stephen P. Hasan, Tayyaba TI Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Review ID SINGLET OXYGEN LUMINESCENCE; INDUCED PROTOPORPHYRIN-IX; SITU LIGHT DOSIMETRY; HAIRLESS MOUSE SKIN; DELTA-AMINOLEVULINIC-ACID; SQUAMOUS-CELL CARCINOMA; IRON-CHELATING AGENTS; BLOOD-FLOW DYNAMICS; RAT PROSTATE TUMOR; MONOACID RING-A AB Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment based upon each patients measured bleaching needs to be attempted. In the case of ALA, lack of PpIX is more likely an indicator that alternative PpIX production methods must be implemented. Parsimonious dosimetry, using surrogate measurements that are clinically acceptable, might strategically help to advance PDT in a medical world that is increasingly cost and time sensitive. Careful attention to methodologies that can identify and advance the most critical dosimetric measurements, either direct or surrogate, are needed to ensure successful incorporation of PDT into niche clinical procedures. C1 [Pogue, Brian W.; Elliott, Jonathan T.; Kanick, Stephen C.; Davis, Scott C.; Samkoe, Kimberley S.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Pogue, Brian W.; Samkoe, Kimberley S.] Geisel Sch Med Dartmouth, Dept Surg, Hanover, NH 03755 USA. [Maytin, Edward V.] Cleveland Clin, Learner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA. [Pereira, Stephen P.] UCL, Inst Liver & Digest Hlth, London NW3 2QG, England. [Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.; Pogue, BW (reprint author), Geisel Sch Med Dartmouth, Dept Surg, Hanover, NH 03755 USA. EM brian.w.pogue@dartmouth.edu FU NIH [P01CA084203] FX This work has been funded by NIH Program Project grant P01CA084203. NR 226 TC 5 Z9 5 U1 5 U2 24 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 APR 7 PY 2016 VL 61 IS 7 BP R57 EP R89 DI 10.1088/0031-9155/61/7/R57 PG 33 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA DJ2EP UT WOS:000374016800001 PM 26961864 ER PT J AU Goessling, W North, TE AF Goessling, Wolfram North, Trista E. TI EnaBILEing Growth in the Fetal Liver SO CELL STEM CELL LA English DT Editorial Material ID STRESS AB Blood stem cells develop at successive sites in the vertebrate embryo, but the functional explanation for this behavior is unknown. Sigurdsson et al. (2016) provide justification for transient fetal liver residence, where select bile acid composition, derived from mother and embryo, provides a protective environment, enabling rapid stem cell expansion. C1 [Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Dana Farber Canc Inst, Gastrointestinal Canc Ctr, 44 Binney St, Boston, MA 02115 USA. [Goessling, Wolfram; North, Trista E.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [North, Trista E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. RP Goessling, W (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA.; Goessling, W (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol, Boston, MA 02115 USA.; Goessling, W (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Gastrointestinal Canc Ctr, 44 Binney St, Boston, MA 02115 USA.; Goessling, W; North, TE (reprint author), Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; North, TE (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. EM wgoessling@partners.org; tnorth@bidmc.harvard.edu OI Goessling, Wolfram/0000-0001-9972-1569 FU NIDDK NIH HHS [R01DK098241, R01DK090311] NR 7 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD APR 7 PY 2016 VL 18 IS 4 BP 427 EP 428 DI 10.1016/j.stem.2016.03.019 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DI8AC UT WOS:000373722100003 PM 27058931 ER PT J AU Callahan, A Abeyruwan, SW Al-Ali, H Sakurai, K Ferguson, AR Popovich, PG Shah, NH Visser, U Bixby, JL Lemmon, VP AF Callahan, Alison Abeyruwan, Saminda W. Al-Ali, Hassan Sakurai, Kunie Ferguson, Adam R. Popovich, Phillip G. Shah, Nigam H. Visser, Ubbo Bixby, John L. Lemmon, Vance P. TI RegenBase: a knowledge base of spinal cord injury biology for translational research SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID GROWTH-FACTOR RECEPTOR; KINASE INHIBITOR SELECTIVITY; THROUGHPUT SCREENING DATA; ACTIVATED PROTEIN-KINASE; BIOASSAY ONTOLOGY BAO; AXON REGENERATION; NEURITE OUTGROWTH; PHENOTYPE ONTOLOGY; GENOME DATABASE; DRUG TARGETS AB Spinal cord injury (SCI) research is a data-rich field that aims to identify the biological mechanisms resulting in loss of function and mobility after SCI, as well as develop therapies that promote recovery after injury. SCI experimental methods, data and domain knowledge are locked in the largely unstructured text of scientific publications, making large scale integration with existing bioinformatics resources and subsequent analysis infeasible. The lack of standard reporting for experiment variables and results also makes experiment replicability a significant challenge. To address these challenges, we have developed RegenBase, a knowledge base of SCI biology. RegenBase integrates curated literature-sourced facts and experimental details, raw assay data profiling the effect of compounds on enzyme activity and cell growth, and structured SCI domain knowledge in the form of the first ontology for SCI, using Semantic Web representation languages and frameworks. RegenBase uses consistent identifier schemes and data representations that enable automated linking among RegenBase statements and also to other biological databases and electronic resources. By querying RegenBase, we have identified novel biological hypotheses linking the effects of perturbagens to observed behavioral outcomes after SCI. RegenBase is publicly available for browsing, querying and download. C1 [Callahan, Alison; Shah, Nigam H.] Stanford Univ, Stanford Ctr Biomed Informat Res, Stanford, CA 94305 USA. [Abeyruwan, Saminda W.; Visser, Ubbo] Univ Miami, Dept Comp Sci, Coral Gables, FL 33146 USA. [Al-Ali, Hassan; Sakurai, Kunie; Bixby, John L.; Lemmon, Vance P.] Univ Miami, Miami Project Cure Paralysis, Sch Med, Miami, FL 33136 USA. [Ferguson, Adam R.] Univ Calif San Francisco, Dept Neurol Surg, Brain & Spinal Injury Ctr BASIC, San Francisco, CA 94143 USA. [Ferguson, Adam R.] San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Popovich, Phillip G.] Ohio State Univ, Ctr Brain & Spinal Cord Repair, Columbus, OH 43210 USA. [Popovich, Phillip G.] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA. [Bixby, John L.; Lemmon, Vance P.] Univ Miami, Ctr Computat Sci, Coral Gables, FL 33146 USA. [Bixby, John L.] Univ Miami, Dept Cellular & Mol Pharmacol, Sch Med, Miami, FL 33136 USA. RP Lemmon, VP (reprint author), Univ Miami, Miami Project Cure Paralysis, Sch Med, Miami, FL 33136 USA.; Lemmon, VP (reprint author), Univ Miami, Ctr Computat Sci, Coral Gables, FL 33146 USA. EM vlemmon@miami.edu RI Lemmon, Vance/A-7410-2010 OI Lemmon, Vance/0000-0003-3550-7576 FU National Institute of Child Health and Human Development [HD057632]; National Institute of Neurological Disorders and Stroke [NS080145]; University of Miami Center for Computational Science; Miami Project to Cure Paralysis FX National Institute of Child Health and Human Development (HD057632); National Institute of Neurological Disorders and Stroke (NS080145); University of Miami Center for Computational Science and the Miami Project to Cure Paralysis. NR 73 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PD APR 7 PY 2016 AR baw040 DI 10.1093/database/baw040 PG 13 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA DJ3GZ UT WOS:000374094100001 ER PT J AU Tan, JL Fogley, RD Flynn, RA Ablain, J Yang, S Saint-Andre, V Fan, ZP Do, BT Laga, AC Fujinaga, K Santoriello, C Greer, CB Kim, YJ Clohessy, JG Bothmer, A Pandell, N Avagyan, S Brogie, JE van Rooijen, E Hagedorn, EJ Shyh-Chang, N White, RM Price, DH Pandolfi, PP Peterlin, BM Zhou, Y Kim, TH Asara, JM Chang, HY Young, RA Zon, LI AF Tan, Justin L. Fogley, Rachel D. Flynn, Ryan A. Ablain, Julien Yang, Song Saint-Andre, Violaine Fan, Zi Peng Do, Brian T. Laga, Alvaro C. Fujinaga, Koh Santoriello, Cristina Greer, Celeste B. Kim, Yoon Jung Clohessy, John G. Bothmer, Anne Pandell, Nicole Avagyan, Serine Brogie, John E. van Rooijen, Ellen Hagedorn, Elliott J. Shyh-Chang, Ng White, Richard M. Price, David H. Pandolfi, Pier Paolo Peterlin, B. Matija Zhou, Yi Kim, Tae Hoon Asara, John M. Chang, Howard Y. Young, Richard A. Zon, Leonard I. TI Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma SO MOLECULAR CELL LA English DT Article ID SMALL NUCLEAR RIBONUCLEOPROTEIN; POLYMERASE-II TRANSCRIPTION; BREAST CELL-GROWTH; RNA-POLYMERASE; P-TEFB; 7SK SNRNA; MALIGNANT-MELANOMA; C-MYC; ELONGATION; CANCER AB Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic RNAs to bind to and be stabilized by HEXIM1. HEXIM1 plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals an important role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma. C1 [Tan, Justin L.; Fogley, Rachel D.; Ablain, Julien; Yang, Song; Santoriello, Cristina; Avagyan, Serine; van Rooijen, Ellen; Hagedorn, Elliott J.; Zhou, Yi; Zon, Leonard I.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Stem Cell Program, Boston, MA 02115 USA. [Tan, Justin L.; Fogley, Rachel D.; Ablain, Julien; Yang, Song; Santoriello, Cristina; Avagyan, Serine; van Rooijen, Ellen; Hagedorn, Elliott J.; Zhou, Yi; Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol,Boston Childrens Hosp, Boston, MA 02115 USA. [Tan, Justin L.; Fogley, Rachel D.; Ablain, Julien; Yang, Song; Santoriello, Cristina; Avagyan, Serine; van Rooijen, Ellen; Hagedorn, Elliott J.; Zhou, Yi; Zon, Leonard I.] Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Flynn, Ryan A.; Do, Brian T.; Chang, Howard Y.] Stanford Univ, Sch Med, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA. [Saint-Andre, Violaine; Fan, Zi Peng; Young, Richard A.] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Saint-Andre, Violaine; Fan, Zi Peng; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Laga, Alvaro C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Fujinaga, Koh; Peterlin, B. Matija] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Fujinaga, Koh; Peterlin, B. Matija] Univ Calif San Francisco, Dept Microbiol, San Francisco, CA 94143 USA. [Fujinaga, Koh; Peterlin, B. Matija] Univ Calif San Francisco, Dept Immunol, San Francisco, CA 94143 USA. [Greer, Celeste B.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. [Kim, Yoon Jung; Kim, Tae Hoon] Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75080 USA. [Clohessy, John G.; Bothmer, Anne; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Canc Res Inst, Beth Israel Deaconess Canc Ctr, Boston, MA 02115 USA. [Clohessy, John G.; Bothmer, Anne; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Dept Pathol & Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Clohessy, John G.; Pandell, Nicole] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Preclin Murine Pharmacogenet Facil, Boston, MA 02115 USA. [Brogie, John E.; Price, David H.] Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. [Shyh-Chang, Ng] Genome Inst Singapore, 60 Biopolis St, Singapore 138672, Singapore. [White, Richard M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [White, Richard M.] Weill Cornell Med Coll, New York, NY 10065 USA. [Asara, John M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct,Dept Med, Boston, MA 02215 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Stem Cell Program, Boston, MA 02115 USA.; Zon, LI (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol,Boston Childrens Hosp, Boston, MA 02115 USA.; Zon, LI (reprint author), Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM zon@enders.tch.harvard.edu OI Shyh-Chang, Ng/0000-0003-3138-9525; Kim, Tae Hoon/0000-0003-3950-7557; Do, Brian/0000-0003-4992-2623 FU Howard Hughes Medical Institute; National Cancer Institute (NIH) [R01CA103846]; Agency for Science, Technology & Research, Singapore National Science Scholarship; NIH [2P01CA120964, 5P30CA006516, R01CA140485, R21AI107067, R01-ES023168, R01-HG004361] FX We thank Min Yuan for her help with the metabolomics studies and Dr. Telmo Henriques for his advice on RNA assays. This work was supported by the Howard Hughes Medical Institute and the National Cancer Institute (NIH) R01CA103846 (to L.I.Z.). L.I.Z. is a founder and stockholder of Fate, Inc.; Scholar Rock; and a scientific advisor for Stemgent. J.L.T. is an Agency for Science, Technology & Research, Singapore National Science Scholarship recipient. C.B.G. is a PhRMA Foundation predoctoral fellow. R.A.Y. is a founder and stockholder of Syros Pharmaceuticals. This work was partially supported by NIH grants 2P01CA120964 (to J.M.A.), 5P30CA006516 (to J.M.A.), R01CA140485 (to T.H.K.), R21AI107067 (to T.H.K.), R01-ES023168 (to H.Y.C), and R01-HG004361 (to H.Y.C). NR 49 TC 3 Z9 3 U1 3 U2 9 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 APR 7 PY 2016 VL 62 IS 1 BP 34 EP 46 DI 10.1016/j.molcel.2016.03.013 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DJ3QB UT WOS:000374119600006 PM 27058786 ER PT J AU Bonaca, MP Bhatt, DL Steg, PG Storey, RF Cohen, M Im, K Ophuis, TO Budaj, A Goto, S Lopez-Sendon, J Diaz, R Dalby, A Van de Werf, F Ardissino, D Montalescot, G Aylward, P Magnani, G Jensen, EC Held, P Braunwald, E Sabatine, MS AF Bonaca, Marc P. Bhatt, Deepak L. Steg, P. Gabriel Storey, Robert F. Cohen, Marc Im, Kyungah Ophuis, Ton Oude Budaj, Andrej Goto, Shinya Lopez-Sendon, Jose Diaz, Rafael Dalby, Anthony Van de Werf, Frans Ardissino, Diego Montalescot, Gilles Aylward, Philip Magnani, Giulia Jensen, Eva C. Held, Peter Braunwald, Eugene Sabatine, Marc S. TI Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y(12) inhibitor withdrawal in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54 SO EUROPEAN HEART JOURNAL LA English DT Article DE Coronary artery disease; Platelet inhibition; P2Y(12) inhibition; Ischaemic risk; Ticagrelor; Antiplatelet therapy; Secondary prevention ID DUAL ANTIPLATELET THERAPY; ELUTING STENT IMPLANTATION; TRIAL; PLACEBO AB Aims Ticagrelor reduced major adverse cardiovascular event (MACE) by 15-16% in patients with prior myocardial infarction (MI) in PEGASUS-TIMI 54. We hypothesized that patients who recently discontinued P2Y(12) inhibition, even years after MI, may be at particular risk of MACE and may derive particular benefit from continuation or reinitiation of therapy. Methods and results Patients in PEGASUS-TIMI 54 were categorized by time from last P2Y12 inhibitor (days: <= 30, >30-360, >360). The risk of MACE and the efficacy of ticagrelor were compared across categories. In the placebo arm, patients who more recently stopped P2Y12 inhibitor therapy had a greater number of risk factors but still had a higher risk of MACE after multivariable adjustment [<= 30 days, hazard ratio (HR)(adj) 1.47, 95% confidence interval (CI) 1.12-1.93, P = 0.0051; 30 days-1 year, HRadj 1.28, 95% CI 0.98-1.67, P = 0.073] compared with those who stopped >1 year prior (P-trend = 0.0097). The benefit of ticagrelor depended on the time from last dose, with HRs (95% CI) for ticagrelor (pooled doses) vs. placebo of 0.73 (0.61-0.87), 0.86 (0.71-1.04), and 1.01 (0.80-1.27), respectively, by category (P-trend for interaction < 0.001). The benefit in those =30 days of stopping was similar regardless of time from MI (< 2 years, HR 0.73, 95% CI 0.60-0.89 vs. >= 2 years, HR 0.71, 95% CI 0.50-1.00). Conclusion The benefit of ticagrelor for long-term secondary prevention in patients with prior MI and at least one additional risk factor appeared more marked in patients continuing on or re-starting after only a brief interruption of P2Y(12) inhibition, when compared with patients who had proved themselves stable more than 2 years from their MI and off P2Y(12) inhibitor therapy for more than a year. The increase in bleeding events with ticagrelor was similar regardless of this time interval. For clinicians considering a strategy of prolonged P2Y12 inhibitor therapy in high-risk patients, these data suggest greater benefit in the continuation of such therapy without interruption after MI, rather than re-initiating such therapy in patients who have remained stable for an extended period. Future analyses may help to clarify further the profile of post-MI patients most likely to benefit from uninterrupted dual antiplatelet therapy. C1 [Bonaca, Marc P.; Bhatt, Deepak L.; Im, Kyungah; Magnani, Giulia; Braunwald, Eugene; Sabatine, Marc S.] Brigham & Womens Hosp, TIMI Study Grp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA. [Steg, P. Gabriel] Hop Bichat Claude Bernard, Dept Cardiol, Assistance Publ, F-75877 Paris, France. [Storey, Robert F.] Univ Sheffield, Sheffield, S Yorkshire, England. [Cohen, Marc] Mt Sinai Sch Med, Newark Beth Israel Med Ctr, Cardiovasc Div, New York, NY USA. [Ophuis, Ton Oude] CWZ Hosp, Nijmegen, Netherlands. [Budaj, Andrej] Grochowski Hosp, Postgrad Med Sch, Warsaw, Poland. [Goto, Shinya] Tokai Univ, Sch Med, Inst Med Sci, Tokyo 151, Japan. [Lopez-Sendon, Jose] Hosp Univ La Paz, Inst Invest La PAZ, Madrid, Spain. [Diaz, Rafael] ECLA, Rosario, Santa Fe, Argentina. [Dalby, Anthony] Milpk Hosp, Johannesburg, South Africa. [Van de Werf, Frans] Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium. [Ardissino, Diego] Azienda Osped Univ Parma, Cardiovasc Div, Parma, Italy. [Montalescot, Gilles] Hop La Pitie Salpetriere, Inst Cardiol, 47 Boul Hop, Paris, France. [Aylward, Philip] Flinders Med Ctr, Cardiac & Crit Care Serv, Div Med, Adelaide, SA, Australia. [Jensen, Eva C.; Held, Peter] AstraZenecaAZ R&D, Molndal, Sweden. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org FU AstraZeneca FX This study was supported by a grant from AstraZeneca. NR 9 TC 17 Z9 17 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD APR 7 PY 2016 VL 37 IS 14 BP 1133 EP 1142 DI 10.1093/eurheartj/ehv531 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DI5SA UT WOS:000373558500013 PM 26491109 ER PT J AU Liu, J You, P Chen, G Fu, X Zeng, X Wang, C Huang, Y An, L Wan, X Navone, N Wu, CL McKeehan, WL Zhang, Z Zhong, W Wang, F AF Liu, J. You, P. Chen, G. Fu, X. Zeng, X. Wang, C. Huang, Y. An, L. Wan, X. Navone, N. Wu, C-L McKeehan, W. L. Zhang, Z. Zhong, W. Wang, F. TI Hyperactivated FRS2 alpha-mediated signaling in prostate cancer cells promotes tumor angiogenesis and predicts poor clinical outcome of patients SO ONCOGENE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TO-MESENCHYMAL TRANSITION; INTRAEPITHELIAL NEOPLASIA; ANDROGEN RECEPTOR; TRANSGENIC MOUSE; STROMAL CELLS; PROGRESSION; EXPRESSION; FGFR1; METASTASIS AB Metastasis of tumors requires angiogenesis, which is comprised of multiple biological processes that are regulated by angiogenic factors. The fibroblast growth factor (FGF) is a potent angiogenic factor and aberrant FGF signaling is a common property of tumors. Yet, how the aberration in cancer cells contributes to angiogenesis in the tumor is not well understood. Most studies of its angiogenic signaling mechanisms have been in endothelial cells. FGF receptor substrate 2 alpha (FRS2 alpha) is an FGF receptor-associated protein required for activation of downstream signaling molecules that include those in the mitogen-activated protein and AKT kinase pathways. Herein, we demonstrated that overactivation and hyperactivity of FRS2 alpha, as well as overexpression of cJUN and HIF1 alpha, were positively correlated with vessel density and progression of human prostate cancer (PCa) toward malignancy. We also demonstrate that FGF upregulated the production of vascular endothelial growth factor A mainly by increasing expression of cJUN and HIF1 alpha. This then promoted recruitment of endothelial cells and vessel formation for the tumor. Tumor angiogenesis in mouse PCa tissues was compromised by tissue-specific ablation of Frs2 alpha in prostate epithelial cells. Depletion of Frs2 alpha expression in human PCa cells and in a preclinical xenograft model, MDA PCa 118b, also significantly suppressed tumor angiogenesis accompanied with decreased tumor growth in the bone. The results underscore the angiogenic role of FRS2 alpha-mediated signaling in tumor epithelial cells in angiogenesis. They provide a rationale for treating PCa with inhibitors of FGF signaling. They also demonstrate the potential of overexpressed FRS2 alpha as a biomarker for PCa diagnosis, prognosis and response to therapies. C1 [Liu, J.; You, P.; Chen, G.; Fu, X.; Zeng, X.; Wang, C.; Huang, Y.; An, L.; McKeehan, W. L.; Wang, F.] Texas A&M Hlth Sci Ctr, Inst Biosci & Technol, Ctr Canc & Stem Cell Biol, Houston, TX USA. [Liu, J.; You, P.; Chen, G.; Fu, X.; Zeng, X.; Wang, C.; Huang, Y.; An, L.; McKeehan, W. L.; Wang, F.] Texas A&M Hlth Sci Ctr, Coll Med, Houston, TX USA. [You, P.; Zhang, Z.] Xiamen Univ, Affiliated Zhongshan Hosp, Xiamen, Peoples R China. [Chen, G.; Fu, X.; Zhong, W.] Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Guangdong Key Lab Clin Mol Med & Diagnost, Dept Urol, Guangzhou, Guangdong, Peoples R China. [Zeng, X.] Jinan Univ, Inst Tissue Transplantat & Immunol, Guangzhou, Guangdong, Peoples R China. [Wang, C.] Wenzhou Med Univ, Coll Pharm, Wenzhou, Peoples R China. [Wan, X.; Navone, N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wu, C-L] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wu, C-L] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Wu, C-L] Harvard Univ, Sch Med, Boston, MA USA. RP Zhang, Z; Zhong, W; Wang, F (reprint author), Texas A&M Univ, Inst Biosci & Technol, 2121 W Holcombe Blvd, Houston, TX 77030 USA. EM zzy11603@163.com; wdezhong@21cn.com; fwang@ibt.tamhsc.edu FU National Institutes of Health [CA96824, DE023106, CA140388]; Cancer Prevention and Research Institution of Texas [CPRIT110555]; National Natural Science Foundation of China [81170699, 81272813, 81101712, 81270761, 510180, 81072016] FX We thank Dr Stefan Siwko and Samantha Del Castillo for critical reading of the manuscript. This work was supported in part by the National Institutes of Health CA96824 and DE023106 to FW, CA140388 to NN, WLM and FW, and The Cancer Prevention and Research Institution of Texas CPRIT110555 to FW and WLM, and the National Natural Science Foundation of China 81170699, 81272813 to CW, 81101712, 81270761 to XL, 510180 to WZ and 81072016 to ZYZ. NR 41 TC 1 Z9 1 U1 2 U2 6 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 APR 7 PY 2016 VL 35 IS 14 BP 1750 EP 1759 DI 10.1038/onc.2015.239 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA DI6LM UT WOS:000373610400002 PM 26096936 ER PT J AU Tagge, I O'Connor, A Chaudhary, P Pollaro, J Berlow, Y Chalupsky, M Bourdette, D Woltjer, R Johnson, M Rooney, W AF Tagge, Ian O'Connor, Audrey Chaudhary, Priya Pollaro, Jim Berlow, Yosef Chalupsky, Megan Bourdette, Dennis Woltjer, Randy Johnson, Mac Rooney, William TI Spatio-Temporal Patterns of Demyelination and Remyelination in the Cuprizone Mouse Model SO PLOS ONE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CORPUS-CALLOSUM; MAGNETIZATION-TRANSFER; SUBVENTRICULAR ZONE; MULTIPLE-SCLEROSIS; WHITE-MATTER; IN-VIVO; REGIONAL HETEROGENEITY; BRAIN; MRI AB Cuprizone administration in mice provides a reproducible model of demyelination and spontaneous remyelination, and has been useful in understanding important aspects of human disease, including multiple sclerosis. In this study, we apply high spatial resolution quantitative MRI techniques to establish the spatio-temporal patterns of acute demyelination in C57BL/6 mice after 6 weeks of cuprizone administration, and subsequent remyelination after 6 weeks of post-cuprizone recovery. MRI measurements were complemented with Black Gold II stain for myelin and immunohistochemical stains for associated tissue changes. Gene expression was evaluated using the Allen Gene Expression Atlas. Twenty-five C57BL/6 male mice were split into control and cuprizone groups; MRI data were obtained at baseline, after 6 weeks of cuprizone, and 6 weeks post-cuprizone. High-resolution (100 mu m isotropic) whole-brain coverage magnetization transfer ratio (MTR) parametric maps demonstrated concurrent caudal-to-rostral and medial-to-lateral gradients of MTR decrease within corpus callosum (CC) that correlated well with demyelination assessed histologically. Our results show that demyelination was not limited to the midsagittal line of the corpus callosum, and also that opposing gradients of demyelination occur in the lateral and medial CC. T-2-weighted MRI gray/white matter contrast was strong at baseline, weak after 6 weeks of cuprizone treatment, and returned to a limited extent after recovery. MTR decreases during demyelination were observed throughout the brain, most clearly in callosal white matter. Myelin damage and repair appear to be influenced by proximity to oligodendrocyte progenitor cell populations and exhibit an inverse correlation with myelin basic protein gene expression. These findings suggest that susceptibility to injury and ability to repair vary across the brain, and whole-brain analysis is necessary to accurately characterize this model. Whole-brain parametric mapping across time is essential for gaining a real understanding of disease processes in-vivo. MTR increases in healthy mice throughout adolescence and adulthood were observed, illustrating the need for appropriate age-matched controls. Elucidating the unique and site-specific demyelination in the cuprizone model may offer new insights into in mechanisms of both damage and repair in human demyelinating diseases. C1 [Tagge, Ian; O'Connor, Audrey; Pollaro, Jim; Berlow, Yosef; Rooney, William] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. [Tagge, Ian; Rooney, William] Oregon Hlth & Sci Univ, Biomed Engn, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. [Chaudhary, Priya; Bourdette, Dennis; Rooney, William] Oregon Hlth & Sci Univ, Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. [Chalupsky, Megan; Woltjer, Randy] Oregon Hlth & Sci Univ, Pathol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. [Bourdette, Dennis] Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. [Johnson, Mac] Vertex Pharmaceut Inc, 50 Northern Ave, Boston, MA 02210 USA. RP Tagge, I; Rooney, W (reprint author), Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM taggei@ohsu.edu; rooneyw@ohsu.edu OI Tagge, Ian/0000-0002-5260-7117 FU Vertex Pharmaceuticals, Inc.; NIA [P30 AG008017] FX The primary funder, Vertex Pharmaceuticals, Inc., provided a grant to investigate MRI biomarkers of myelination which supported experimental costs and partial salary support for authors AO'C, JP, IT, and WR, 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. MJ, on behalf of Vertex Pharmaceuticals, Inc., contributed to study design insofar as suggesting the use of cuprizone in mice to validate MRI biomarkers of myelin content in-vivo. The funders had no role in data acquisition, processing, or analysis. MJ reviewed the paper prior to submission and offered comments on presentation, but otherwise did not have a role in the decision to publish.; Evan Calkins, Danielle Galipeau, and David Clark provided excellent technical support in histological processing. We would like to express our thanks to the Advanced Light Microscopy Core (P30 NS061800) Facility at the Oregon Health & Science University. Immunohistochemical studies were performed in the laboratory of the Oregon Brain Bank and the Oregon Alzheimer's Disease Center (supported by NIA P30 AG008017). NR 60 TC 3 Z9 3 U1 3 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 APR 7 PY 2016 VL 11 IS 4 AR e0152480 DI 10.1371/journal.pone.0152480 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI6KO UT WOS:000373608000021 PM 27054832 ER PT J AU Wen, Y Alshikho, MJ Herbert, MR AF Wen, Ya Alshikho, Mohamad J. Herbert, Martha R. TI Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling SO PLOS ONE LA English DT Article ID PROTEIN-KINASE-C; SET ENRICHMENT ANALYSIS; SPECTRUM DISORDERS; SFARI GENE; RISK; DYSFUNCTION; ACTIVATION; MUTATIONS; PREVALENCE; METABOLISM AB We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging-they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)-and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as themost enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process "calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK" is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG's category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic conditions and heart diseases. ASDsmay thus arise, or emerge, from underlying vulnerabilities related to pleiotropic genes associated with pervasively important molecular mechanisms, vulnerability to environmental input andmultiple systemic co-morbidities. C1 [Wen, Ya; Alshikho, Mohamad J.; Herbert, Martha R.] Massachusetts Gen Hosp, Dept Neurol, TRANSCEND Res, Charlestown, MA USA. [Wen, Ya; Alshikho, Mohamad J.; Herbert, Martha R.] Harvard Univ, Sch Med, Boston, MA USA. [Wen, Ya; Herbert, Martha R.] Higher Synth Fdn, Cambridge, MA USA. RP Wen, Y; Herbert, MR (reprint author), Massachusetts Gen Hosp, Dept Neurol, TRANSCEND Res, Charlestown, MA USA.; Wen, Y; Herbert, MR (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Wen, Y; Herbert, MR (reprint author), Higher Synth Fdn, Cambridge, MA USA. EM ywen3@mgh.harvard.edu; martha.herbert@mgh.harvard.edu RI Wen, Ya/M-6341-2016 OI Wen, Ya/0000-0003-0134-8853 NR 54 TC 6 Z9 6 U1 2 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 APR 7 PY 2016 VL 11 IS 4 AR e0153329 DI 10.1371/journal.pone.0153329 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI6KO UT WOS:000373608000121 PM 27055244 ER PT J AU Chouchani, ET Kazak, L Jedrychowski, MP Lu, GNZ Erickson, BK Szpyt, J Pierce, KA Laznik-Bogoslavski, D Vetrivelan, R Clish, CB Robinson, AJ Gygi, SP Spiegelman, BM AF Chouchani, Edward T. Kazak, Lawrence Jedrychowski, Mark P. Lu, Gina Z. Erickson, Brian K. Szpyt, John Pierce, Kerry A. Laznik-Bogoslavski, Dina Vetrivelan, Ramalingam Clish, Clary B. Robinson, Alan J. Gygi, Steve P. Spiegelman, Bruce M. TI Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1 SO NATURE LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; BROWN ADIPOSE-TISSUE; UNCOUPLING PROTEIN-1; MASS-SPECTROMETRY; CHEMICAL PROBES; REDOX STATE; ADIPOCYTES; EXPRESSION; DIMEDONE; FAT AB Brown and beige adipose tissues can dissipate chemical energy as heat through thermogenic respiration, which requires uncoupling protein 1 (UCP1)(1,2). Thermogenesis from these adipocytes can combat obesity and diabetes(3), encouraging investigation of factors that control UCP1-dependent respiration in vivo. Here we show that acutely activated thermogenesis in brown adipose tissue is defined by a substantial increase in levels of mitochondrial reactive oxygen species (ROS). Remarkably, this process supports in vivo thermogenesis, as pharmacological depletion of mitochondrial ROS results in hypothermia upon cold exposure, and inhibits UCP1-dependent increases in whole-body energy expenditure. We further establish that thermogenic ROS alter the redox status of cysteine thiols in brown adipose tissue to drive increased respiration, and that Cys253 of UCP1 is a key target. UCP1 Cys253 is sulfenylated during thermogenesis, while mutation of this site desensitizes the purine-nucleotide-inhibited state of the carrier to adrenergic activation and uncoupling. These studies identify mitochondrial ROS induction in brown adipose tissue as a mechanism that supports UCP1-dependent thermogenesis and whole-body energy expenditure, which opens the way to improved therapeutic strategies for combating metabolic disorders. C1 [Chouchani, Edward T.; Kazak, Lawrence; Lu, Gina Z.; Laznik-Bogoslavski, Dina; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Chouchani, Edward T.; Kazak, Lawrence; Jedrychowski, Mark P.; Lu, Gina Z.; Erickson, Brian K.; Szpyt, John; Gygi, Steve P.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Pierce, Kerry A.; Clish, Clary B.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Vetrivelan, Ramalingam] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Robinson, Alan J.] MRC, Mitochondrial Biol Unit, Hills Rd, Cambridge CB2 0XY, England. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.; Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU JPB Foundation; National Institutes of Health [DK31405]; Human Frontiers Science Program; Canadian Institutes for Health Research FX Supported by the JPB Foundation and National Institutes of Health (DK31405) to B.M.S. and by grants from Human Frontiers Science Program (to E.T.C.) and the Canadian Institutes for Health Research (to L.K.). We acknowledge M. Murphy, Y. Kirichok, and A. Bertholet for many discussions. We also thank M. Murphy for providing MitoQ. NR 50 TC 24 Z9 24 U1 17 U2 46 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 APR 7 PY 2016 VL 532 IS 7597 BP 112 EP + DI 10.1038/nature17399 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI5RE UT WOS:000373555500044 PM 27027295 ER PT J AU Petzold, G Fischer, ES Thoma, NH AF Petzold, Georg Fischer, Eric S. Thomae, Nicolas H. TI Structural basis of lenalidomide-induced CK1 alpha degradation by the CRL4(CRBN) ubiquitin ligase SO NATURE LA English DT Article ID MULTIPLE-MYELOMA; DEL(5Q) MDS; THALIDOMIDE; COMPLEX; ACTIVATION; CEREBLON; TARGET; IKAROS; CELLS; QUANTIFICATION AB Thalidomide and its derivatives, lenalidomide and pomalidomide, are immune modulatory drugs (IMiDs) used in the treatment of haematologic malignancies(1,2). IMiDs bind CRBN, the substrate receptor of the CUL4-RBX1-DDB1-CRBN (also known as CRL4(CRBN)) E3 ubiquitin ligase(3), and inhibit ubiquitination of endogenous CRL4CRBN substrates(4). Unexpectedly, IMiDs also repurpose the ligase to target new proteins for degradation. Lenalidomide induces degradation of the lymphoid transcription factors Ikaros and Aiolos (also known as IKZF1 and IKZF3)(5-7), and casein kinase 1 alpha (CK1 alpha)(8), which contributes to its clinical efficacy in the treatment of multiple myeloma(5) and 5q-deletion associated myelodysplastic syndrome (del(5q) MDS)(8), respectively. How lenalidomide alters the specificity of the ligase to degrade these proteins remains elusive. Here we present the 2.45 angstrom crystal structure of DDB1-CRBN bound to lenalidomide and CK1 alpha. CRBN and lenalidomide jointly provide the binding interface for a CK1 alpha beta-hairpin-loop located in the kinase N-lobe. We show that CK1 alpha binding to CRL4(CRBN) is strictly dependent on the presence of an IMiD. Binding of IKZF1 to CRBN similarly requires the compound and both, IKZF1 and CK1 alpha, use a related binding mode. Our study provides a mechanistic explanation for the selective efficacy of lenalidomide in del(5q) MDS therapy(8,9). We anticipate that high-affinity protein-protein interactions induced by small molecules will provide opportunities for drug development, particularly for targeted protein degradation. C1 [Petzold, Georg; Fischer, Eric S.; Thomae, Nicolas H.] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland. [Petzold, Georg; Fischer, Eric S.; Thomae, Nicolas H.] Univ Basel, Peterspl 10, CH-4003 Basel, Switzerland. [Fischer, Eric S.] Dana Farber Canc Inst, Dept Canc Biol, LC-4312,360 Longwood Ave, Boston, MA 02215 USA. [Fischer, Eric S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Thoma, NH (reprint author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.; Thoma, NH (reprint author), Univ Basel, Peterspl 10, CH-4003 Basel, Switzerland. EM nicolas.thoma@fmi.ch FU Novartis Research Foundation; Swiss National Science Foundation [31003A_144020]; European Research Council [ERC-2014-ADG 666068]; European Molecular Biology Organization (EMBO) [ALTF-1350-2013]; Human Frontier Science Program (HFSP) [LT000210/2014] FX This work was supported by the Novartis Research Foundation, the Swiss National Science Foundation (31003A_144020) and the European Research Council (ERC-2014-ADG 666068 CsnCRL). G.P. was supported by Long-Term Fellowships of the European Molecular Biology Organization (EMBO; ALTF-1350-2013) and the Human Frontier Science Program (HFSP; LT000210/2014). We thank G. M. Lingaraju for the DDB1Delta BPB construct, M. Faty for assistance with protein purifications, J. Rabl and S. Kassube for help during diffraction data collection, R. Bunker for support with data processing and model building, W. A. Rahman and A. Potenza for assistance with fluorescence polarization, W. C. Forrester for help and comments, and J. Seebacher, R. Sack, D. Hess and M. Stadler for help with mass spectrometry experiments. We acknowledge the Paul Scherrer Institute for provision of synchrotron radiation beam time at beamline PXII and PXIII of the SLS and would like to thank M. Wang for assistance. NR 41 TC 6 Z9 6 U1 10 U2 21 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 APR 7 PY 2016 VL 532 IS 7597 BP 127 EP + DI 10.1038/nature16979 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI5RE UT WOS:000373555500047 PM 26909574 ER PT J AU Berenson, RA Goodson, JD AF Berenson, Robert A. Goodson, John D. TI Finding Value in Unexpected Places - Fixing the Medicare Physician Fee Schedule SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PAYMENT C1 [Berenson, Robert A.] Urban Inst, Washington, DC 20037 USA. [Goodson, John D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Berenson, RA (reprint author), Urban Inst, Washington, DC 20037 USA. NR 5 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 APR 7 PY 2016 VL 374 IS 14 BP 1306 EP 1309 DI 10.1056/NEJMp1600999 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DI3UW UT WOS:000373425000004 PM 26959109 ER PT J AU Rossi, PJ Gunduz, A Judy, J Wilson, L Machado, A Giordano, JJ Elias, WJ Rossi, MA Butson, CL Fox, MD McIntyre, CC Pouratian, N Swann, NC de Hemptinne, C Gross, RE Chizeck, HJ Tagliati, M Lozano, AM Goodman, W Langevin, JP Alterman, RL Akbar, U Gerhardt, GA Grill, WM Hallett, M Herrington, T Herron, J van Horne, C Kopell, BH Lang, AE Lungu, C Martinez-Ramirez, D Mogilner, AY Molina, R Opri, E Otto, KJ Oweiss, KG Pathak, Y Shukla, A Shute, J Sheth, SA Shih, LC Steinke, GK Troster, AI Vanegas, N Zaghloul, KA Cendejas-Zaragoza, L Verhagen, L Foote, KD Okun, MS AF Rossi, P. Justin Gunduz, Aysegul Judy, Jack Wilson, Linda Machado, Andre Giordano, James J. Elias, W. Jeff Rossi, Marvin A. Butson, Christopher L. Fox, Michael D. McIntyre, Cameron C. Pouratian, Nader Swann, Nicole C. de Hemptinne, Coralie Gross, Robert E. Chizeck, Howard J. Tagliati, Michele Lozano, Andres M. Goodman, Wayne Langevin, Jean-Philippe Alterman, Ron L. Akbar, Umer Gerhardt, Greg A. Grill, Warren M. Hallett, Mark Herrington, Todd Herron, Jeffrey van Horne, Craig Kopell, Brian H. Lang, Anthony E. Lungu, Codrin Martinez-Ramirez, Daniel Mogilner, Alon Y. Molina, Rene Opri, Enrico Otto, Kevin J. Oweiss, Karim G. Pathak, Yagna Shukla, Aparna Shute, Jonathan Sheth, Sameer A. Shih, Ludy C. Steinke, G. Karl Troester, Alexander I. Vanegas, Nora Zaghloul, Kareem A. Cendejas-Zaragoza, Leopoldo Verhagen, Leonard Foote, Kelly D. Okun, Michael S. TI Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies SO FRONTIERS IN NEUROSCIENCE LA English DT Review DE deep brain stimulation; local field potentials; neuromodulation; closed-loop; electrodes ID POSTTRAUMATIC-STRESS-DISORDER; FOCUSED ULTRASOUND THALAMOTOMY; PARKINSONS-DISEASE; ESSENTIAL TREMOR; SUBTHALAMIC NUCLEUS; TOURETTE SYNDROME; MOVEMENT-DISORDERS; LATERAL HABENULA; GLOBUS-PALLIDUS; DEPRESSION AB The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies. C1 [Rossi, P. Justin; Gunduz, Aysegul; Judy, Jack; Martinez-Ramirez, Daniel; Molina, Rene; Opri, Enrico; Otto, Kevin J.; Oweiss, Karim G.; Shukla, Aparna; Shute, Jonathan; Foote, Kelly D.; Okun, Michael S.] Univ Florida, Dept Neurosci, Ctr Movement Disorders & Neurorestorat, Gainesville, FL 32610 USA. [Wilson, Linda] Int Technol Roadmap Semicond, Washington, DC USA. [Machado, Andre] Cleveland Clin, Neurol Inst, Cleveland, OH 44106 USA. [Giordano, James J.] Georgetown Univ, Med Ctr, Dept Neurol, Neuroeth Studies Program, Washington, DC 20007 USA. [Elias, W. Jeff] Univ Virginia, Hlth Sci Ctr, Dept Neurosurg, Neurol Surg & Neurol,Stereotact & Funct Neurosurg, Charlottesville, VA 22908 USA. [Rossi, Marvin A.; Cendejas-Zaragoza, Leopoldo; Verhagen, Leonard] Rush Univ, Med Ctr, Dept Neurol, Chicago, IL 60612 USA. [Butson, Christopher L.] Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT USA. [Fox, Michael D.; Alterman, Ron L.; Shih, Ludy C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [McIntyre, Cameron C.] Case Western Reserve Univ, Dept Biomed Engn, Sch Med, Cleveland, OH 44106 USA. [Pouratian, Nader] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA. [Swann, Nicole C.; de Hemptinne, Coralie] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gross, Robert E.] Emory Univ, Emory Clin, Atlanta, GA 30322 USA. [Chizeck, Howard J.; Herron, Jeffrey] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. [Tagliati, Michele] Cedars Sinai Med Ctr, Dept Neurol, Movement Disorders Program, Los Angeles, CA 90048 USA. [Lozano, Andres M.; Lang, Anthony E.] Univ Toronto, Dept Neurosurg, Toronto, ON, Canada. [Goodman, Wayne; Kopell, Brian H.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Langevin, Jean-Philippe] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Akbar, Umer] Brown Univ, Dept Neurol, Alpert Med Sch, Providence, RI 02912 USA. [Gerhardt, Greg A.; van Horne, Craig] Univ Kentucky, Med Ctr, Lexington, KY USA. [Grill, Warren M.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. [Hallett, Mark; Lungu, Codrin; Zaghloul, Kareem A.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Herrington, Todd] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mogilner, Alon Y.] NYU, Dept Neurosurg, Ctr Neuromodulat, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA. [Pathak, Yagna; Sheth, Sameer A.; Vanegas, Nora] Columbia Univ, Med Ctr, Neurol Inst, New York, NY USA. [Steinke, G. Karl] Boston Sci Neuromodulat, Valencia, CA USA. [Troester, Alexander I.] Barrow Neurol Inst, Dept Clin Neuropsychol, Phoenix, AZ 85013 USA. RP Rossi, PJ (reprint author), Univ Florida, Dept Neurosci, Ctr Movement Disorders & Neurorestorat, Gainesville, FL 32610 USA. EM pjrossi@ufl.edu RI Martinez-Ramirez, Daniel/H-2546-2016; Gunduz, Aysegul/Q-2336-2016; OI Martinez-Ramirez, Daniel/0000-0001-8003-0610; Mogilner, Alon/0000-0003-1493-0463 FU NICHD NIH HHS [T32 HD043730]; NINDS NIH HHS [R01 NS040894, R37 NS040894] NR 103 TC 2 Z9 2 U1 13 U2 29 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD APR 6 PY 2016 VL 10 AR 119 DI 10.3389/fnins.2016.00119 PG 15 WC Neurosciences SC Neurosciences & Neurology GA DI4GU UT WOS:000373459200001 PM 27092042 ER PT J AU Holmes, AJ Hollinshead, MO Roffman, JL Smoller, JW Buckner, RL AF Holmes, Avram J. Hollinshead, Marisa O. Roffman, Joshua L. Smoller, Jordan W. Buckner, Randy L. TI Individual Differences in Cognitive Control Circuit Anatomy Link Sensation Seeking, Impulsivity, and Substance Use SO JOURNAL OF NEUROSCIENCE LA English DT Article DE brain anatomy; cognitive control; impulsivity; individual differences; sensation seeking; substance use ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HUMAN CEREBRAL-CORTEX; CORTICAL THICKNESS; DRUG-ADDICTION; RISK-TAKING; EXTERNALIZING PROBLEMS; DECISION-MAKING; BRAIN STRUCTURE; SELF-CONTROL; PERSONALITY AB Individuals vary widely in their tendency to seek stimulation and act impulsively, early developing traits with genetic origins. Failures to regulate these behaviors increase risk for maladaptive outcomes including substance abuse. Here, we explored the neuroanatomical correlates of sensation seeking and impulsivity in healthy young adults. Our analyses revealed links between sensation seeking and reduced cortical thickness that were preferentially localized to regions implicated in cognitive control, including anterior cingulate and middle frontal gyrus (n = 1015). These associations generalized to self-reported motor impulsivity, replicated in an independent group (n = 219), and correlated with heightened alcohol, tobacco, and caffeine use. Critically, the relations between sensation seeking and brain structure were evident in participants without a history of alcohol or tobacco use, suggesting that observed associations with anatomy are not solely a consequence of substance use. These results demonstrate that individual differences in the tendency to seek stimulation, act on impulse, and engage in substance use are correlated with the anatomical structure of cognitive control circuitry. Our findings suggest that, in healthy populations, covariation across these complex multidimensional behaviors may in part originate from a common underlying biology. C1 [Holmes, Avram J.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Holmes, Avram J.; Roffman, Joshua L.; Smoller, Jordan W.; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Holmes, Avram J.; Roffman, Joshua L.; Smoller, Jordan W.; Buckner, Randy L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Holmes, Avram J.; Hollinshead, Marisa O.; Roffman, Joshua L.; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Hollinshead, Marisa O.; Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, 33 Kirkland St, Cambridge, MA 02138 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Holmes, AJ (reprint author), Yale Univ, Dept Psychol, 402 Sheffield Sterling Strathcona Hall, New Haven, CT 06511 USA. EM avram.holmes@yale.edu FU Simons Foundation; Howard Hughes Medical Institute; National Institute of Mental Health [R01-MH079799, K24MH094614, K01MH099232]; Center for Brain Science Neuroinformatics Research Group; Athinoula A. Martinos Center for Biomedical Imaging; Center for Human Genetics Research; [1S10RR023043]; [1S10RR023401] FX This work was supported by the Simons Foundation (R.L.B.), the Howard Hughes Medical Institute (R.L.B.), and the National Institute of Mental Health (Grants R01-MH079799 and K24MH094614 to J.W.S. and Grant K01MH099232 to A.J.H.). This research was made possible by the resources provided through Shared Instrumentation Grants 1S10RR023043 and 1S10RR023401. Data were provided in part by the Brain Genomics Superstruct Project of Harvard University and Massachusetts General Hospital (Principal Investigators: R.L.B., J.L.R., and J.W.S.) with support from the Center for Brain Science Neuroinformatics Research Group, the Athinoula A. Martinos Center for Biomedical Imaging, and the Center for Human Genetics Research. JWS is a Tepper Family MGH Research Scholar. We thank Justin Baker, Arielle Baskin-Sommers, Matt Hutchison, Marcia Johnson, and Lauren Patrick for their feedback on early versions of this manuscript; Timothy O'Keefe, Victor Petrov, and Gabriele Fariello for neuroinformatics support; and the Harvard FAS Research Computing for high-performance computing support. NR 70 TC 4 Z9 4 U1 9 U2 21 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 APR 6 PY 2016 VL 36 IS 14 BP 4038 EP 4049 DI 10.1523/JNEUROSCI.3206-15.2016 PG 12 WC Neurosciences SC Neurosciences & Neurology GA DI4GC UT WOS:000373457400014 PM 27053210 ER PT J AU Xu, WM Nathwani, B Lin, CX Wan, J Karatekin, E Pincet, F Shih, W Rothman, JE AF Xu, Weiming Nathwani, Bhavik Lin, Chenxiang Wan, Jing Karatekin, Erdem Pincet, Frederic Shih, William Rothman, James E. TI A Programmable DNA Origami Platform to Organize SNAREs for Membrane Fusion SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID LATERAL MOBILITY; NANOSCALE SHAPES; LIPID-BILAYERS; ANCHORED DNA; FOLDING DNA; VESICLE; PROTEINS; COMPLEX; ENERGETICS; ASSAY AB Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes are the core molecular machinery of membrane fusion, a fundamental process that drives inter- and intracellular communication and trafficking. One of the questions that remains controversial has been whether and how SNAREs cooperate. Here we show the use of self-assembled DNA-nanostructure rings to template uniform-sized small unilamellar vesicles containing predetermined maximal number of externally facing SNAREs to study the membrane-fusion process. We also incorporated lipid-conjugated complementary ssDNA as tethers into vesicle and target membranes, which enabled bypass of the rate-limiting docking step of fusion reactions and allowed direct observation of individual membrane-fusion events at SNARE densities as low as one pair per vesicle. With this platform, we confirmed at the single event level that, after docking of the templated-SUVs to supported lipid bilayers (SBL), one to two pairs of SNAREs are sufficient to drive fast lipid mixing. Modularity and programmability of this platform makes it readily amenable to studying more complicated systems where auxiliary proteins are involved. C1 [Xu, Weiming; Lin, Chenxiang; Wan, Jing; Pincet, Frederic; Rothman, James E.] Yale Univ, Sch Med, Dept Cell Biol, West Haven, CT 06516 USA. [Xu, Weiming; Wan, Jing; Karatekin, Erdem; Pincet, Frederic; Rothman, James E.] Yale Univ, Nanobiol Inst, West Haven, CT 06516 USA. [Nathwani, Bhavik; Lin, Chenxiang; Shih, William] Harvard Univ, Sch Med, Wyss Inst Biol Inspired Engn & Biol Chem & Mol Ph, Boston, MA 02115 USA. [Nathwani, Bhavik; Lin, Chenxiang; Shih, William] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Karatekin, Erdem] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, 260 Whitney Ave, New Haven, CT 06520 USA. [Karatekin, Erdem] Yale Univ, Dept Mol Biophys & Biochem, 260 Whitney Ave, New Haven, CT 06520 USA. [Karatekin, Erdem] Univ Paris 05, CNRS, Fac Sci Fondamentales & Biomed, Lab Neurophoton,UMR8250, 45 Rue St Peres, F-75270 Paris 06, France. [Pincet, Frederic] Univ Paris Diderot, Univ Paris 06, Ecole Normale Super Paris, Lab Phys Stat,CNRS,UMR 8550, 24 Rue Lhomond, F-75005 Paris, France. RP Rothman, JE (reprint author), Yale Univ, Sch Med, Dept Cell Biol, West Haven, CT 06516 USA.; Rothman, JE (reprint author), Yale Univ, Nanobiol Inst, West Haven, CT 06516 USA.; Shih, W (reprint author), Harvard Univ, Sch Med, Wyss Inst Biol Inspired Engn & Biol Chem & Mol Ph, Boston, MA 02115 USA.; Shih, W (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM william.shih@wyss.harvard.edu; james.rothman@yale.edu OI Lin, Chenxiang/0000-0001-7041-1946 FU US National Institutes of Health (NIH) Grant [DK027044-39]; Agence Nationale de la Recherche (ANR) [ANR-14-1CHN-0022-01]; National Institutes of Health (NIH) Director's New Innovator Award [DP2-GM114830, DP2-OD004641]; NIH grant [R21-GM109466, R01GM108954]; Yale University faculty startup fund; Army Research Office MURI grant [W911NF-12-1-0420]; National Science Foundation Expeditions Grant [1317694]; Wyss Institute for Biologically Inspired Engineering Faculty Award; Kavli Neuroscience Scholar Award FX We thank Dr. Y Gao for discussions on the cross-linking reactions. This work was supported by US National Institutes of Health (NIH) Grant DK027044-39 and Agence Nationale de la Recherche (ANR) ANR-14-1CHN-0022-01 grant to J.E.R, by a National Institutes of Health (NIH) Director's New Innovator Award (DP2-GM114830), an NIH grant (R21-GM109466) and a Yale University faculty startup fund to C.L., by an NIH Director's New Innovator Award (DP2-OD004641), an Army Research Office MURI grant (W911NF-12-1-0420), National Science Foundation Expeditions Grant (1317694), and a Wyss Institute for Biologically Inspired Engineering Faculty Award to W.M.S, and an NIH grant R01GM108954 and a Kavli Neuroscience Scholar Award to E.K. NR 47 TC 3 Z9 3 U1 13 U2 57 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 APR 6 PY 2016 VL 138 IS 13 BP 4439 EP 4447 DI 10.1021/jacs.5b13107 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA DI8JT UT WOS:000373748000031 PM 26938705 ER PT J AU Atukunda, EC Mugyenyi, GR Obua, C Atuhumuza, EB Musinguzi, N Tornes, YF Agaba, AG Siedner, MJ AF Atukunda, Esther Cathyln Mugyenyi, Godfrey Rwambuka Obua, Celestino Atuhumuza, Elly Bronney Musinguzi, Nicholas Tornes, Yarine Fajardo Agaba, Amon Ganaafa Siedner, Mark Jacob TI Measuring Post-Partum Haemorrhage in Low-Resource Settings: The Diagnostic Validity of Weighed Blood Loss versus Quantitative Changes in Hemoglobin SO PLOS ONE LA English DT Article ID SUBLINGUAL MISOPROSTOL; VISUAL ESTIMATION; TRIAL; DELIVERY AB Background Accurate estimation of blood loss is central to prompt diagnosis and management of postpartum hemorrhage (PPH), which remains a leading cause of maternal mortality in low-resource countries. In such settings, blood loss is often estimated visually and subjectively by attending health workers, due to inconsistent availability of laboratory infrastructure. We evaluated the diagnostic accuracy of weighed blood loss (WBL) versus changes in peri-partum hemoglobin to detect PPH. Methods Data from this analysis were collected as part of a randomized controlled trial comparing oxytocin with misoprostol for PPH (NCT01866241). Blood samples for complete blood count were drawn on admission and again prior to hospital discharge or before blood transfusion. During delivery, women were placed on drapes and had pre-weighed sanitary towels placed around their perineum. Blood was then drained into a calibrated container and the sanitary towels were added to estimate WBL, where each gram of blood was estimated as a milliliter. Sensitivity, specificity, negative and positive predictive values (PPVs) were calculated at various blood volume loss and time combinations, and we fit receiver-operator curves using blood loss at 1, 2, and 24 hours compared to a reference standard of haemoglobin decrease of >10%. Results A total of 1,140 women were enrolled in the study, of whom 258 (22.6%) developed PPH, defined as a haemoglobin drop >10%, and 262 (23.0%) had WBL >= 500mL. WBL generally had a poor sensitivity for detection of PPH (<75% for most volume-time combinations). In contrast, the specificity of WBL was high with blood loss >= 500mL at 1h and >= 750mL at any time points excluding PPH in over 97% of women. As such, WBL has a high PPV (>85%) in high prevalence settings when WBL exceeds 750mL. Conclusion WBL has poor sensitivity but high specificity compared to laboratory-based methods of PPH diagnosis. These characteristics correspond to a high PPV in areas with high PPH prevalence. Although WBL is not useful for excluding PPH, this low-cost, simple and reproducible method is promising as a reasonable method to identify significant PPH in such settings where quantifiable red cell indices are unavailable. C1 [Atukunda, Esther Cathyln; Mugyenyi, Godfrey Rwambuka; Obua, Celestino; Atuhumuza, Elly Bronney; Musinguzi, Nicholas; Tornes, Yarine Fajardo; Agaba, Amon Ganaafa] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Siedner, Mark Jacob] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Siedner, Mark Jacob] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Siedner, Mark Jacob] Harvard Univ, Sch Med, Boston, MA USA. RP Atukunda, EC (reprint author), Mbarara Univ Sci & Technol, Mbarara, Uganda. EM estheratukunda@gmail.com FU Father Bash Foundation; Divine Mercy Hospital scholarship [FBF PS1981]; National Institutes of Health [MH K23099916] FX This study was funded by the Father Bash Foundation and Divine Mercy Hospital scholarship awards to ECA (FBF PS1981). MJS receives support from the National Institutes of Health (MH K23099916). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 0 Z9 0 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 6 PY 2016 VL 11 IS 4 AR e0152408 DI 10.1371/journal.pone.0152408 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI6IX UT WOS:000373603500039 PM 27050823 ER PT J AU Sharma, S Toledo, O Hedden, M Lyon, KF Brooks, SB David, RP Limtong, J Newsome, JM Novakovic, N Rajasekaran, S Thapar, V Williams, SR Schiller, MR AF Sharma, Surbhi Toledo, Oniel Hedden, Michael Lyon, Kenneth F. Brooks, Steven B. David, Roxanne P. Limtong, Justin Newsome, Jacklyn M. Novakovic, Nemanja Rajasekaran, Sanguthevar Thapar, Vishal Williams, Sean R. Schiller, Martin R. TI The Functional Human C-Terminome SO PLOS ONE LA English DT Article ID MODULAR PROTEIN DOMAINS; MINIMOTIF MINER; MOLECULAR-BIOLOGY; DATABASE; RESOURCE; INFORMATION; SEQUENCES; MOTIFS; PREDICTION; SIGNATURES AB All translated proteins end with a carboxylic acid commonly called the C-terminus. Many short functional sequences (minimotifs) are located on or immediately proximal to the C-terminus. However, information about the function of protein C-termini has not been consolidated into a single source. Here, we built a new "C-terminome" database and web system focused on human proteins. Approximately 3,600 C-termini in the human proteome have a minimotif with an established molecular function. To help evaluate the function of the remaining C-termini in the human proteome, we inferred minimotifs identified by experimentation in rodent cells, predicted minimotifs based upon consensus sequence matches, and predicted novel highly repetitive sequences in C-termini. Predictions can be ranked by enrichment scores or Gene Evolutionary Rate Profiling (GERP) scores, a measurement of evolutionary constraint. By searching for new anchored sequences on the last 10 amino acids of proteins in the human proteome with lengths between 3-10 residues and up to 5 degenerate positions in the consensus sequences, we have identified new consensus sequences that predict instances in the majority of human genes. All of this information is consolidated into a database that can be accessed through a C-terminome web system with search and browse functions for minimotifs and human proteins. A known consensus sequence-based predicted function is assigned to nearly half the proteins in the human proteome. Weblink: http://cterminome.bio-toolkit.com. C1 [Sharma, Surbhi; Toledo, Oniel; Hedden, Michael; Lyon, Kenneth F.; Brooks, Steven B.; David, Roxanne P.; Limtong, Justin; Newsome, Jacklyn M.; Novakovic, Nemanja; Williams, Sean R.; Schiller, Martin R.] Univ Nevada, Nevada Inst Personalized Med, Las Vegas, NV 89154 USA. [Sharma, Surbhi; Toledo, Oniel; Hedden, Michael; Lyon, Kenneth F.; Brooks, Steven B.; David, Roxanne P.; Limtong, Justin; Newsome, Jacklyn M.; Novakovic, Nemanja; Williams, Sean R.; Schiller, Martin R.] Univ Nevada, Sch Life Sci, Las Vegas, NV 89154 USA. [Rajasekaran, Sanguthevar] Univ Connecticut, Dept Comp Sci & Engn, Storrs, CT 06269 USA. [Thapar, Vishal] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Schiller, MR (reprint author), Univ Nevada, Nevada Inst Personalized Med, Las Vegas, NV 89154 USA.; Schiller, MR (reprint author), Univ Nevada, Sch Life Sci, Las Vegas, NV 89154 USA. EM martin.schiller@unlv.edu FU National Institutes of Health [R15 GM107983, R01 GM079689, R01 LM010101]; Graduate and Professional Students Association, University of Nevada, Las Vegas FX This work was supported by the National Institutes of Health (http://www.nih.gov) grants R15 GM107983, R01 GM079689 to MRS, and R01 LM010101 to SR. The Graduate and Professional Students Association, University of Nevada, Las Vegas also funded SS. NR 54 TC 0 Z9 0 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 6 PY 2016 VL 11 IS 4 AR e0152731 DI 10.1371/journal.pone.0152731 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI6IX UT WOS:000373603500051 PM 27050421 ER PT J AU Secemsky, EA Kirtane, A Bangalore, S Ferro, E Wimmer, N Roe, M Dai, D Mauri, L Yeh, R AF Secemsky, Eric Alexander Kirtane, Ajay Bangalore, Sripal Ferro, Enrico Wimmer, Neil Roe, Matthew Dai, Dadi (David) Mauri, Laura Yeh, Robert TI EFFECTIVENESS OF BIVALIRUDIN VERSUS UNFRACTIONATED HEPARIN DURING PERCUTANEOUS CORONARY INTERVENTION AMONG PATIENTS WITH ACUTE MYOCARDIAL INFARCTION IN THE UNITED STATES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Secemsky, Eric Alexander; Kirtane, Ajay; Bangalore, Sripal; Ferro, Enrico; Wimmer, Neil; Roe, Matthew; Dai, Dadi (David); Mauri, Laura; Yeh, Robert] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1241M-01 BP 20 EP 20 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188700021 ER PT J AU Iwata, H Osborn, E Ughi, G Murakami, K Goettsch, C Hutcheson, J Mauskapf, A Mattson, P Libby, P Aikawa, E Tearney, G Aikawa, M Jaffer, F AF Iwata, Hiroshi Osborn, Eric Ughi, Giovanni Murakami, Kentaro Goettsch, Claudia Hutcheson, Joshua Mauskapf, Adam Mattson, Peter Libby, Peter Aikawa, Elena Tearney, Guillermo Aikawa, Masanori Jaffer, Farouc TI A HIGHLY SELECTIVE PPAR. AGONIST K-877 SUPPRESSES NEOINTIMA FORMATION FOLLOWING CORONARY STENTING IN SWINE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 4 U2 4 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 APR 5 PY 2016 VL 67 IS 13 SU S MA 1143-153 BP 156 EP 156 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188700157 ER PT J AU Secemsky, EA Butala, N Kartoun, U Mahmood, S Shaw, S Yeh, R AF Secemsky, Eric Alexander Butala, Neel Kartoun, Uri Mahmood, Sadiqa Shaw, Stanley Yeh, Robert TI USE OF ORAL ANTICOAGULANT THERAPY AMONG REAL-WORLD PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Secemsky, Eric Alexander; Butala, Neel; Kartoun, Uri; Mahmood, Sadiqa; Shaw, Stanley; Yeh, Robert] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1144-175 BP 178 EP 178 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701022 ER PT J AU Higuma, T Soeda, T Yamada, M Yokoyama, H Yokota, T Izumiyama, K Nishizaki, F Minami, Y Xing, L Lee, H Okumura, K Jang, IK AF Higuma, Takumi Soeda, Tsunenari Yamada, Masahiro Yokoyama, Hiroaki Yokota, Takashi Izumiyama, Kei Nishizaki, Fumie Minami, Yoshiyasu Xing, Lei Lee, Hang Okumura, Ken Jang, Ik-Kyung TI RESIDUAL THROMBUS PATTERN IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION CAUSED BY PLAQUE EROSION, PLAQUE RUPTURE, VERSUS CALCIFIED NODULE AFTER ASPIRATION THROMBECTOMY: AN OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Higuma, Takumi; Soeda, Tsunenari; Yamada, Masahiro; Yokoyama, Hiroaki; Yokota, Takashi; Izumiyama, Kei; Nishizaki, Fumie; Minami, Yoshiyasu; Xing, Lei; Lee, Hang; Okumura, Ken; Jang, Ik-Kyung] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1177-179 BP 262 EP 262 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701106 ER PT J AU Gaggin, HK Liu, YY Lyass, A Van Kimmenade, R Motiwala, S Kelly, N Mallick, A Gandhi, P Ibrahim, N Simon, M Belcher, A Harisiades, J Massaro, J D'Agostino, R Januzzi, J AF Gaggin, Hanna Kim Liu, Yuyin Lyass, Asya Van Kimmenade, Roland Motiwala, Shweta Kelly, Noreen Mallick, Aditi Gandhi, Parul Ibrahim, Nasrien Simon, Mandy Belcher, Arianna Harisiades, Jamie Massaro, Joseph D'Agostino, Ralph Januzzi, James TI COMPREHENSIVE ASSESSMENT OF TYPE 2 MYOCARDIAL INFARCTION IN AT-RISK PATIENTS: RESULTS FROM THE CATHETER SAMPLED BLOOD ARCHIVE IN CARDIOVASCULAR DISEASES (CASABLANCA) STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Res Clin Inst, 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1222-117 BP 282 EP 282 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701126 ER PT J AU Vidula, M Duran, J Partida, R Coppolino, W Naderi, S Wood, M AF Vidula, Mahesh Duran, Jessica Partida, Ramon Coppolino, Whitney Naderi, Sahar Wood, Malissa TI PATIENTS WITH SPONTANEOUS CORONARY ARTERY DISSECTION DEMONSTRATE WALL MOTION ABNORMALITIES CONSISTENT WITH TAKOTSUBO CARDIOMYOPATHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Vidula, Mahesh; Duran, Jessica; Partida, Ramon; Coppolino, Whitney; Naderi, Sahar; Wood, Malissa] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1224-153 BP 318 EP 318 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701162 ER PT J AU Secemsky, EA Kirtane, A Bangalore, S Ferro, E Wimmer, N Roe, M Dai, D Mauri, L Yeh, R AF Secemsky, Eric Alexander Kirtane, Ajay Bangalore, Sripal Ferro, Enrico Wimmer, Neil Roe, Matthew Dai, Dadi (David) Mauri, Laura Yeh, Robert TI TEMPORAL TRENDS AND OPERATOR VARIATION IN ANTICOAGULANT USE DURING PERCUTANEOUS CORONARY INTERVENTION FOR PATIENTS WITH ACUTE MYOCARDIAL INFARCTION IN THE UNITED STATES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Secemsky, Eric Alexander; Kirtane, Ajay; Bangalore, Sripal; Ferro, Enrico; Wimmer, Neil; Roe, Matthew; Dai, Dadi (David); Mauri, Laura; Yeh, Robert] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1283M-05 BP 465 EP 465 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701309 ER PT J AU Silverman, MG Cannon, C Blazing, M Mach, F Zhou, J Tershakovec, A Giugliano, R AF Silverman, Michael G. Cannon, Christopher Blazing, Michael Mach, Francois Zhou, Jing Tershakovec, Andrew Giugliano, Robert TI LONG TERM SIGNIFICANCE OF HEART FAILURE COMPLICATING ACUTE MYOCARDIAL INFARCTION IN 11,185 PATIENTS FROM THE IMPROVED REDUCTION OF OUTCOMES: VYTORIN EFFICACY INTERNATIONAL TRIAL (IMPROVE-IT) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Silverman, Michael G.; Cannon, Christopher; Blazing, Michael; Mach, Francois; Zhou, Jing; Tershakovec, Andrew; Giugliano, Robert] TIMI Study Grp, 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1100-012 BP 484 EP 484 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701328 ER PT J AU Xu, HY Wiviott, SD Sabatine, MS Gao, XJ Yang, JG Wang, Y Yang, YJ AF Xu, Haiyan Wiviott, Stephen D. Sabatine, Marc S. Gao, Xiaojin Yang, Jingang Wang, Yang Yang, Yuejin TI OUTCOMES AND READMISSION RATE WITHIN 30 DAYS AND 6 MONTHS AFTER ACUTE MYOCARDIAL INFARCTION IN CHINA: DATA FROM THE CHINA ACUTE MYOCARDIAL INFARCTION REGISTRY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Fuwai Hosp, Natl Ctr Cardiovasc Dis, Beijing, Peoples R China. Brigham & Womens Hosp, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 0 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1100-034 BP 506 EP 506 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701350 ER PT J AU Bittner, D Takx, R Staziaki, P Janjua, S Meyersohn, N Lu, M Prabhakar, A Nagurney, J Hoffmann, U Ghoshhajra, B AF Bittner, Daniel Takx, Richard Staziaki, Pedro Janjua, Sumbal Meyersohn, Nandini Lu, Michael Prabhakar, Anand Nagurney, John Hoffmann, Udo Ghoshhajra, Brian TI PREDICTIVE VALUE OF CORONARY ARTERY CALCIFICATION AND THROMBOLYSIS IN MYOCARDIAL INFARCTION RISK SCORE IN THE ASSESSMENT OF PATIENTS WITH ACUTE CHEST PAIN: RESULTS FROM AN EMERGENCY DEPARTMENT REGISTRY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Bittner, Daniel; Takx, Richard; Staziaki, Pedro; Janjua, Sumbal; Meyersohn, Nandini; Lu, Michael; Prabhakar, Anand; Nagurney, John; Hoffmann, Udo; Ghoshhajra, Brian] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1132-005 BP 515 EP 515 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701359 ER PT J AU Rozen, G Heist, K Acha, MR Ptaszek, L Ruskin, J Mansour, M AF Rozen, Guy Heist, Kevin Acha, Moshe Rav Ptaszek, Leon Ruskin, Jeremy Mansour, Moussa TI UTILIZATION OF AN ADVANCED ABLATION LESION ANNOTATION SYSTEM WITH FORCE SENSING CATHETERS DRAMATICALLY REDUCES ADENOSINE INDUCED PULMONARY VEIN RECONNECTION FOLLOWING RADIOFREQUENCY ABLATION FOR ATRIAL FIBRILLATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Rozen, Guy; Heist, Kevin; Acha, Moshe Rav; Ptaszek, Leon; Ruskin, Jeremy; Mansour, Moussa] Massachusetts Gen Hosp, Boston, MA 02114 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1117-346 BP 719 EP 719 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701563 ER PT J AU Flannery, L Fahed, A Barinsky, G Youniss, M Yeh, DD Bhatt, A AF Flannery, Laura Fahed, Akl Barinsky, Gregory Youniss, Mohamed Yeh, Doreen Defaria Bhatt, Ami TI ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISK IN ADULTS WITH CONGENITAL HEART DISEASE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Flannery, Laura; Fahed, Akl; Barinsky, Gregory; Youniss, Mohamed; Yeh, Doreen Defaria; Bhatt, Ami] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1126M-03 BP 899 EP 899 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701743 ER PT J AU Stefanescu, A Monteleone, P Wood, M Troyanos, C d'Hemecourt, PA Dyer, S Rosenfield, K Baggish, A AF Stefanescu, Ada Monteleone, Peter Wood, Malissa Troyanos, Chris d'Hemecourt, Pierre A. Dyer, Sophia Rosenfield, Kenneth Baggish, Aaron TI HEART DISEASE ON HEARTBREAK HILL: ATYPICAL ACUTE CORONARY SYNDROME DURING THE BOSTON MARATHON SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Stefanescu, Ada; Monteleone, Peter; Wood, Malissa; Troyanos, Chris; d'Hemecourt, Pierre A.; Dyer, Sophia; Rosenfield, Kenneth; Baggish, Aaron] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Stefanescu Schmidt, Ada/0000-0002-5692-2616 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1185-286 BP 1148 EP 1148 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188701992 ER PT J AU Gaggin, HK Rabideau, D Ibrahim, N Gandhi, P Januzzi, J AF Gaggin, Hanna Kim Rabideau, Dustin Ibrahim, Nasrien Gandhi, Parul Januzzi, James TI ASSESSMENT OF SERIAL HEART RATE AND BETA BLOCKER USE IN A CONTEMPORARY CHRONIC SYSTOLIC HEART FAILURE PATIENTS: RESULTS FROM THE PROBNP OUTPATIENT TAILORED CHRONIC HEART FAILURE (PROTECT) STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Res Clin Inst, 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1102-060 BP 1316 EP 1316 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702162 ER PT J AU Ibrahim, NE Gaggin, HK Rabideau, DJ Januzzi, J AF Ibrahim, Nasrien E. Gaggin, Hanna K. Rabideau, Dustin J. Januzzi, James TI WORSENING RENAL FUNCTION DURING AGGRESSIVE HEART FAILURE MANAGEMENT IS NOT ASSOCIATED WITH POOR OUTCOMES: RESULTS FROM THE PRO-BNP OUTPATIENT TAILORED CHRONIC HEART FAILURE THERAPY (PROTECT) STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Ibrahim, Nasrien E.; Gaggin, Hanna K.; Rabideau, Dustin J.; Januzzi, James] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1102-095 BP 1339 EP 1339 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702185 ER PT J AU Do, JM Ly, S Brown, J Joseph, J AF Do, Jacquelyn-My Ly, Samantha Brown, Jason Joseph, Jacob TI IMPACT OF STAKEHOLDER-DRIVEN INSTITUTIONAL CHANGES ON HEART FAILURE OUTCOMES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Do, Jacquelyn-My; Ly, Samantha; Brown, Jason; Joseph, Jacob] VA Boston Healthcare Syst, West Roxbury, 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1171-055 BP 1413 EP 1413 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702259 ER PT J AU Houstis, N Eisman, A Pappagianopoulos, P Wagner, PD Lewis, G AF Houstis, Nicholas Eisman, Aaron Pappagianopoulos, Paul Wagner, Peter D. Lewis, Gregory TI EXERCISE INTOLERANCE IN HFPEF: THE CRITICAL ROLE OF SKELETAL MUSCLE DIFFUSION CAPACITY AND THE CHALLENGE OF MULTIPLE OXYGEN TRANSPORT DEFECTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Houstis, Nicholas; Eisman, Aaron; Pappagianopoulos, Paul; Wagner, Peter D.; Lewis, Gregory] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1217-094 BP 1481 EP 1481 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702327 ER PT J AU Ferencik, M Lu, MT Mayrhofer, T Ivanov, A Adami, E Sengupta, S Rogers, C Hoffmann, U AF Ferencik, Maros Lu, Michael T. Mayrhofer, Thomas Ivanov, Alexander Adami, Elizabeth Sengupta, Souma Rogers, Campbell Hoffmann, Udo TI NON-INVASIVE FRACTIONAL FLOW RESERVE DERIVED FROM CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH ACUTE CHEST PAIN: RESULTS FROM THE ROMICAT II TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1244M-03 BP 1576 EP 1576 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702422 ER PT J AU Truong, QA Szymonifka, J Picard, M Thai, WE Heist, BWE Xiong, GL Cheung, J Hoffmann, U Singh, J AF Truong, Quynh A. Szymonifka, Jackie Picard, Michael Thai, Wai-Ee Heist, Bryan Wai Edwin Xiong, Guanglei Cheung, Jim Hoffmann, Udo Singh, Jagmeet TI DUAL-SOURCE COMPUTED TOMOGRAPHY TO IMPROVE PREDICTION OF RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY (DIRECT): A PROSPECTIVE DOUBLE-BLIND RANDOMIZED STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 New York Presbyterian Hosp, New York, NY USA. Weill Cornell Med Coll, New York, NY USA. 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 911-08 BP 1588 EP 1588 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702434 ER PT J AU Ali, A Takx, R Ishai, A Tawakol, A AF Ali, Abdelrahman Takx, Richard Ishai, Amorina Tawakol, Ahmed TI HEIGHTENED HEPATIC METABOLISM ASSOCIATES WITH SUB-CLINICAL ATHEROSCLEROSIS AND INCREASED RISK OF CARDIOVASCULAR DISEASE EVENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1112-237 BP 1615 EP 1615 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702461 ER PT J AU Lo, C Brown, M Contursi, M Lewis, G Lieberman, D Baggish, A AF Lo, Claire Brown, Marcel Contursi, Miranda Lewis, Gregory Lieberman, Daniel Baggish, Aaron TI CHARACTERIZATION OF CORTISOL KINETICS AT DIFFERENT RUNNING INTENSITIES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Cambridge, MA 02138 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1113-257 BP 1635 EP 1635 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702481 ER PT J AU Meller, S Chatterjee, N Dhakal, B Pappagianopoulos, P Eisman, A Bailey, CS Baggish, A Malhotra, R Lewis, G AF Meller, Stephanie Chatterjee, Neal Dhakal, Bishnu Pappagianopoulos, Paul Eisman, Aaron Bailey, Cole S. Baggish, Aaron Malhotra, Rajeev Lewis, Gregory TI METABOLIC COST OF UNLOADED VERSUS RAMP EXERCISE: MECHANISMS OF EXERCISE INTOLERANCE IN HEART FAILURE PRESERVED EJECTION FRACTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Meller, Stephanie; Chatterjee, Neal; Dhakal, Bishnu; Pappagianopoulos, Paul; Eisman, Aaron; Bailey, Cole S.; Baggish, Aaron; Malhotra, Rajeev; Lewis, Gregory] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Malhotra, Rajeev/0000-0003-0120-4630 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1113-258 BP 1636 EP 1636 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702482 ER PT J AU Finch, JAM Chiampas, G Mutharasan, RK Contursi, M D'Hemecourt, P Dyer, S Troyanos, C Baggish, A AF Finch, Jennifer Ann Michaud Chiampas, George Mutharasan, R. Kannan Contursi, Miranda D'Hemecourt, Pierre Dyer, Sophia Troyanos, Chris Baggish, Aaron TI ELECTROCARDIOGRAM UTILIZATION IN THE MARATHON MEDICAL TENT SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Feinberg Sch Med, Bank Amer Chicago Marathon, Chicago, IL 60611 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1113-260 BP 1638 EP 1638 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702484 ER PT J AU Wasfy, MM DeLuca, JR Foster, C Weiner, R Lewis, G Hutter, A Picard, M Di Carli, M Baggish, A AF Wasfy, Meagan Murphy DeLuca, James R. Foster, Courtney Weiner, Rory Lewis, Gregory Hutter, Adolph Picard, Michael Di Carli, Marcelo Baggish, Aaron TI PRESERVED MYOCARDIAL METABOLIC EFFICIENCY IN EXERCISE-INDUCED LEFT VENTRICULAR HYPERTROPHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Wasfy, Meagan Murphy; DeLuca, James R.; Foster, Courtney; Weiner, Rory; Lewis, Gregory; Hutter, Adolph; Picard, Michael; Di Carli, Marcelo; Baggish, Aaron] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1113-261 BP 1639 EP 1639 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702485 ER PT J AU Bennet, C Abeya, FC Hoffman, A Rwebembera, J Wood, M Picard, M Okello, S AF Bennet, Catherine Abeya, Fardous Charles Hoffman, Ari Rwebembera, Joselyn Wood, Malissa Picard, Michael Okello, Samson TI FOCUSED, ABBREVIATED TRAINING IN THE PERFORMANCE AND INTERPRETATION OF TRANSTHORACIC ECHOCARDIOGRAPHY SHOWS PROMISE IN RURAL UGANDA SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Mbarara Univ Sci & Technol, Mbarara, Uganda. Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Okello, Samson/0000-0001-7377-6094 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1149-266 BP 1660 EP 1660 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702506 ER PT J AU Nakamura, K Elmariah, S Pomerantsev, E Leavitt, M Inglessis, I Palacios, I Passeri, J AF Nakamura, Kenta Elmariah, Sammy Pomerantsev, Eugene Leavitt, Marcia Inglessis, Ignacio Palacios, Igor Passeri, Jonathan TI ECHOCARDIOGRAPHIC ASSESSMENT OF CALCIFIC MITRAL STENOSIS OVERESTIMATES SEVERITY COMPARED TO RHEUMATIC MITRAL STENOSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Nakamura, Kenta; Elmariah, Sammy; Pomerantsev, Eugene; Leavitt, Marcia; Inglessis, Ignacio; Palacios, Igor; Passeri, Jonathan] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1183-231 BP 1700 EP 1700 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702546 ER PT J AU Janjua, SA Massaro, J Chuang, M D'Agostino, R Hoffmann, U O'Donnell, C AF Janjua, Sumbal Ashraf Massaro, Joseph Chuang, Michael D'Agostino, Ralph Hoffmann, Udo O'Donnell, Christopher TI THRESHOLDS FOR ABDOMINAL AORTIC CALCIUM THAT PREDICT CARDIOVASCULAR DISEASE EVENTS IN THE FRAMINGHAM HEART STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Janjua, Sumbal Ashraf; Massaro, Joseph; Chuang, Michael; D'Agostino, Ralph; Hoffmann, Udo; O'Donnell, Christopher] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1184-261 BP 1737 EP 1737 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702583 ER PT J AU Meyersohn, N Janjua, S Staziaki, P Bittner, D Takx, R Weiner, R Wasfy, J Hoffmann, U Ghoshhajra, B AF Meyersohn, Nandini Janjua, Sumbal Staziaki, Pedro Bittner, Daniel Takx, Richard Weiner, Rory Wasfy, Jason Hoffmann, Udo Ghoshhajra, Brian TI MEDICAL MANAGEMENT OF NON-OBSTRUCTIVE CORONARY ARTERY DISEASE ON CORONARY CT ANGIOGRAPHY: INSIGHT FROM A MODERN EMERGENCY DEPARTMENT CLINICAL REGISTRY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Meyersohn, Nandini; Janjua, Sumbal; Staziaki, Pedro; Bittner, Daniel; Takx, Richard; Weiner, Rory; Wasfy, Jason; Hoffmann, Udo; Ghoshhajra, Brian] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1230-246 BP 1763 EP 1763 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702609 ER PT J AU Teo, E Hung, J Teoh, J Yucel, E Bamira, D Khan, A Zeng, X AF Teo, Eliza Hung, Judy Teoh, Jonathan Yucel, Evin Bamira, Daniel Khan, Asaad Zeng, Xin TI DIFFERENTIAL EFFECTS OF DOBUTAMINE AND EXERCISE ON LEFT VENTRICULAR VOLUMES DURING STRESS ECHOCARDIOGRAPHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Teo, Eliza; Hung, Judy; Teoh, Jonathan; Yucel, Evin; Bamira, Daniel; Khan, Asaad; Zeng, Xin] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1231-259 BP 1784 EP 1784 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702630 ER PT J AU Khera, AV Demler, OV Adelman, SJ Collins, H Glynn, R Ridker, P Rader, D Mora, S AF Khera, Amit V. Demler, Olga V. Adelman, Steven J. Collins, Heidi Glynn, Robert Ridker, Paul Rader, Daniel Mora, Samia TI CHOLESTEROL EFFLUX CAPACITY, HDL-PARTICLE NUMBER, AND INCIDENT CARDIOVASCULAR EVENTS: RESULTS FROM THE JUPITER TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1213M-01 BP 1851 EP 1851 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702697 ER PT J AU Januzzi, JL Gaggin, H Lyass, A Trebnick, A Massaro, J D'Agostino, R O'Donnell, C Wang, T Ramachandran, V AF Januzzi, James L. Gaggin, Hanna Lyass, Asya Trebnick, April Massaro, Joseph D'Agostino, Ralph O'Donnell, Christopher Wang, Thomas Ramachandran, Vasan TI CONCENTRATIONS OF PRO-NEUROTENSIN, CARDIAC STRUCTURE, AND CORONARY ARTERY CALCIUM IN THE COMMUNITY: THE FRAMINGHAM HEART STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Clin Res Inst, 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1120-396 BP 1903 EP 1903 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702749 ER PT J AU Ladapo, JA Coles, A Dolor, R Mark, D Cooper, L Lee, K Goldberg, J Shapiro, M Hoffmann, U Douglas, P AF Ladapo, Joseph A. Coles, Adrian Dolor, Rowena Mark, Daniel Cooper, Lawton Lee, Kerry Goldberg, Jonathan Shapiro, Michael Hoffmann, Udo Douglas, Pamela TI PATTERNS OF PREVENTIVE MEDICAL THERAPY AND LIFESTYLE PRACTICES IN PATIENTS EVALUATED FOR SUSPECTED CORONARY ARTERY DISEASE: THE PROMISE TRIAL (PROSPECTIVE MULTICENTER IMAGING STUDY FOR EVALUATION OF CHEST PAIN) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1156-369 BP 1910 EP 1910 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702756 ER PT J AU Kaneko, M Uno, H AF Kaneko, Masayuki Uno, Hajime TI ISSUES OF CONVENTIONAL META-ANALYSIS FOR TIME-TO-EVENT OUTCOMES: REANALYSIS RESULTS OF THE EFFICACY AND SAFETY OF NOVEL ORAL ANTICOAGULANTS VERSUS WARFARIN IN PATIENTS WITH ATRIAL FIBRILLATION USING RECONSTRUCTED INDIVIDUAL-LEVEL DATA SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Kitasato Univ, Grad Sch Pharmaceut Sci, Tokyo, Japan. Dana Farber Canc Inst, Boston, MA 02115 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1191-375 BP 1949 EP 1949 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702795 ER PT J AU Garg, A Sharma, A Krishnamoorthy, P Bagae, S Mukherjee, D AF Garg, Aakash Sharma, Abhishek Krishnamoorthy, Parasuram Bagae, Solomon Mukherjee, Debabrata TI ROLE OF NIACIN IN CURRENT CLINICAL PRACTICE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROL TRIALS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Garg, Aakash; Sharma, Abhishek; Krishnamoorthy, Parasuram; Bagae, Solomon; Mukherjee, Debabrata] James J Peters VA Hosp, Bronx, NY 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1271-383 BP 2025 EP 2025 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702871 ER PT J AU Blumenthal, DM Olenski, A Yeh, R DeFaria-Yeh, D Wood, M Jena, A AF Blumenthal, Daniel Mark Olenski, Andrew Yeh, Robert DeFaria-Yeh, Doreen Wood, Malissa Jena, Anupam TI SEX DIFFERENCES IN ACADEMIC RANK AMONG CARDIOLOGISTS AT US MEDICAL SCHOOLS IN 2014 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU 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 APR 5 PY 2016 VL 67 IS 13 SU S MA 1271-393 BP 2035 EP 2035 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702881 ER PT J AU Grapsa, J Tan, TC Durighel, G Nihoyannopoulos, P AF Grapsa, Julia Tan, Timothy C. Durighel, Giuliana Nihoyannopoulos, Petros TI INTERVENTRICULAR SEPTAL DISPLACEMENT WITHIN THE CARDIAC CYCLE PREDICTS MORTALITY IN PATIENTS WITH PRE-CAPILLARY PULMONARY HYPERTENSION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Imperial Coll NHS Trust, London, England. 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1265-312 BP 2077 EP 2077 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702923 ER PT J AU Psotka, M Schiller, N Whooley, M Mishra, R AF Psotka, Mitchell Schiller, Nelson Whooley, Mary Mishra, Rakesh TI ASSOCIATION OF FIVE-YEAR CHANGE IN N-TERMINAL FRAGMENT OF THE PROHORMONE BRAIN-TYPE NATRIURETIC PEPTIDE WITH CHANGE IN LEFT VENTRICULAR MASS AND INCIDENT HYPERTROPHY IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE: THE HEART AND SOUL STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1124M-09 BP 2084 EP 2084 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702930 ER PT J AU Fordyce, CB Douglas, PS Roberts, RS Patel, MR Hoffmann, U Mark, DB Al-Khalidi, H Kostis, J Lee, KL Udelson, JE AF Fordyce, Christopher B. Douglas, Pamela S. Roberts, Rhonda S. Patel, Manesh R. Hoffmann, Udo Mark, Daniel B. Al-Khalidi, Hussein Kostis, John Lee, Kerry L. Udelson, James E. TI IDENTIFYING STABLE CHEST PAIN PATIENTS WITH SUSPECTED CORONARY DISEASE IN WHOM NONINVASIVE TESTING MAY BE SAFELY DEFERRED: INSIGHTS FROM THE PROMISE TRIAL (PROSPECTIVE MULTICENTER IMAGING STUDY FOR EVALUATION OF CHEST PAIN) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Duke Clin Res Inst, Durham, NC USA. 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1195M-03 BP 2092 EP 2092 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702938 ER PT J AU Voora, D Coles, A Lee, K Hoffmann, U Wingrove, J Rhees, B Huang, L Daniels, S Monane, M Rosenberg, S Mark, D Shah, S Kraus, W Ginsburg, G Douglas, P AF Voora, Deepak Coles, Adrian Lee, Kerry Hoffmann, Udo Wingrove, James Rhees, Brian Huang, Lin Daniels, Susan Monane, Mark Rosenberg, Steven Mark, Daniel Shah, Svati Kraus, William Ginsburg, Geoffrey Douglas, Pamela TI AN AGE- AND SEX-SPECIFIC PERIPHERAL BLOOD GENE EXPRESSION SCORE CORRELATES WITH FUTURE CARDIOVASCULAR EVENTS: INSIGHTS FROM THE PROMISE TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Duke Clin Res Inst, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1206M-01 BP 2094 EP 2094 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702940 ER PT J AU Hemal, K Pagidipati, N Coles, A Dolor, R Mark, D Pellikka, P Hoffmann, U Litwin, S Daubert, M Shah, S Ariani, K Bullock-Palmer, R Lee, K Douglas, P AF Hemal, Kshipra Pagidipati, Neha Coles, Adrian Dolor, Rowena Mark, Daniel Pellikka, Patricia Hoffmann, Udo Litwin, Sheldon Daubert, Melissa Shah, Svati Ariani, Kevin Bullock-Palmer, Renee Lee, Kerry Douglas, Pamela TI SEX DIFFERENCES IN DEMOGRAPHICS, RISK FACTORS AND PRESENTATION IN STABLE CONTEMPORARY OUTPATIENTS WITH SUSPECTED CORONARY ARTERY DISEASE: INSIGHTS FROM THE PROMISE TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Duke Clin Res Inst, Durham, NC USA. 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1206M-03 BP 2095 EP 2095 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702941 ER PT J AU Desai, N Scirica, B Steg, P McGuire, D Mosenzon, O Im, K Raz, I Braunwald, E Bhatt, D AF Desai, Nihar Scirica, Benjamin Steg, Philippe McGuire, Darren Mosenzon, Ofri Im, Kelly Raz, Itamar Braunwald, Eugene Bhatt, Deepak TI PATTERNS OF ASPIRIN UTILIZATION AND OUTCOMES AMONG PATIENTS WITH DIABETES MELLITUS: A PROPENSITY SCORE MATCHED ANALYSIS FROM THE SAVOR-TIMI 53 TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 TIMI Study Grp, Boston, MA USA. Yale Univ, Sch Med, New Haven, CT 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1240M-01 BP 2099 EP 2099 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702945 ER PT J AU Ishai, A Takx, R Nahrendorf, M Pitman, R Lisa, SM Tawakol, A AF Ishai, Amorina Takx, Richard Nahrendorf, Matthias Pitman, Roger Lisa, Shin M. Tawakol, Ahmed TI GREATER ACTIVITY OF THE BRAIN'S EMOTIONAL STRESS CENTER ASSOCIATES WITH ARTERIAL INFLAMMATION AND PREDICTS SUBSEQUENT CVD EVENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Ishai, Amorina; Takx, Richard; Nahrendorf, Matthias; Pitman, Roger; Lisa, Shin M.; Tawakol, Ahmed] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1275M-03 BP 2103 EP 2103 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702949 ER PT J AU Valle, J Graham, L Thiruvoipati, T Armstrong, E Hawn, MT Maddox, T Bradley, S AF Valle, Javier Graham, Laura Thiruvoipati, Thejasvi Armstrong, Ehrin Hawn, Mary T. Maddox, Thomas Bradley, Steven TI IS PREOPERATIVE STRESS TESTING ASSOCIATED WITH 30-DAY POSTOPERATIVE MORTALITY IN PATIENTS PRIOR PCI UNDERGOING NONCARDIAC SURGERY: INSIGHTS FROM THE VETERANS AFFAIRS HEALTH CARE SYSTEM SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 912-04 BP 2110 EP 2110 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702956 ER PT J AU May, EAB Morrow, D Cannon, C Giugliano, R Blazing, M He, P Murphy, S Jennifer, W Kesaniemi, A Pedersen, T Brady, AJ Mitchel, YB Tershakovec, A Braunwald, E AF May, Erin Ann Bohula Morrow, David Cannon, Christopher Giugliano, Robert Blazing, Michael He, Ping Murphy, Sabina Jennifer, White Kesaniemi, Antero Pedersen, Terje Brady, Adrian J. Mitchel, Yale B. Tershakovec, Andrew Braunwald, Eugene TI ATHEROTHROMBOTIC RISK STRATIFICATION AND EZETIMIBE USE IN IMPROVE-IT SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [May, Erin Ann Bohula; Morrow, David; Cannon, Christopher; Giugliano, Robert; Blazing, Michael; He, Ping; Murphy, Sabina; Jennifer, White; Kesaniemi, Antero; Pedersen, Terje; Brady, Adrian J.; Mitchel, Yale B.; Tershakovec, Andrew; Braunwald, Eugene] TIMI Study Grp, 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1140-103 BP 2129 EP 2129 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702975 ER PT J AU Bansilal, S Bonaca, M Cornel, JH Storey, R Bhatt, D Steg, P Im, K Held, P Jensen, E Braunwald, E Sabatine, M Ophuis, TO AF Bansilal, Sameer Bonaca, Marc Cornel, J. H. Storey, Robert Bhatt, Deepak Steg, Philippe Im, Kelly Held, Peter Jensen, Eva Braunwald, Eugene Sabatine, Marc Ophuis, Ton Oude TI EFFICACY AND SAFETY OF TICAGRELOR FOR LONG-TERM SECONDARY PREVENTION OF ATHEROTHROMBOTIC EVENTS IN PATIENTS WITH PRIOR MI AND MULTIVESSEL CORONARY DISEASE: INSIGHTS FROM THE PEGASUS-TIMI 54 TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Bansilal, Sameer; Bonaca, Marc; Cornel, J. H.; Storey, Robert; Bhatt, Deepak; Steg, Philippe; Im, Kelly; Held, Peter; Jensen, Eva; Braunwald, Eugene; Sabatine, Marc; Ophuis, Ton Oude] Brigham & Womens Hosp, TIMI Study Grp, 75 Francis St, Boston, MA 02115 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1220-100 BP 2146 EP 2146 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188702992 ER PT J AU Hariharan, P Dudzinski, D Rosovsky, R MacMahon, P Haddad, F Okechukwu, I Parry, B Chang, YC Kabrhel, C AF Hariharan, Praveen Dudzinski, David Rosovsky, Rachel MacMahon, Peter Haddad, Faris Okechukwu, Ikenna Parry, Blair Chang, Yuchiao Kabrhel, Christopher TI ASSOCIATION OF HIGH CLOT BURDEN IN PULMONARY EMBOLISM WITH RIGHT HEART STRAIN AND IMMEDIATE ADVERSE CLINICAL EVENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Hariharan, Praveen; Dudzinski, David; Rosovsky, Rachel; MacMahon, Peter; Haddad, Faris; Okechukwu, Ikenna; Parry, Blair; Chang, Yuchiao; Kabrhel, Christopher] 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1198M-03 BP 2248 EP 2248 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188703096 ER PT J AU Gutierrez, A Bonaca, M Cannon, C Giugliano, R Park, JG White, JA Tershakovec, A Braunwald, E AF Gutierrez, Antonio Bonaca, Marc Cannon, Christopher Giugliano, Robert Park, Jeong-Gun White, Jennifer A. Tershakovec, Andrew Braunwald, Eugene TI POLYVASCULAR DISEASE, DIABETES MELLITUS AND LONG-TERM VASCULAR RISK: INSIGHTS FROM THE IMPROVE-IT TIMI 40 TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 TIMI Study Grp, Boston, MA USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 1289M-07 BP 2264 EP 2264 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188703112 ER PT J AU Elmariah, S Farrell, LA Maureen, D Shi, X Keyes, MJ Cain, CH Pomerantsev, E Vlahakes, G Inglessis, I Passeri, J Palacios, I Fox, C Rhee, EP Gerszten, R AF Elmariah, Sammy Farrell, Laurie A. Maureen, Daher Shi, Xu Keyes, Michelle J. Cain, Carolyn H. Pomerantsev, Eugene Vlahakes, Gus Inglessis, Ignacio Passeri, Jonathan Palacios, Igor Fox, Caroline Rhee, Eugene P. Gerszten, Robert TI METABOLITE PROFILES PREDICT ACUTE KIDNEY INJURY AND MORTALITY IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 65th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY APR 02-04, 2016 CL Chicago, IL SP Amer Coll Cardiol C1 [Elmariah, Sammy; Farrell, Laurie A.; Maureen, Daher; Shi, Xu; Keyes, Michelle J.; Cain, Carolyn H.; Pomerantsev, Eugene; Vlahakes, Gus; Inglessis, Ignacio; Passeri, Jonathan; Palacios, Igor; Fox, Caroline; Rhee, Eugene P.; Gerszten, Robert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2016 VL 67 IS 13 SU S MA 914-5 BP 2351 EP 2351 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK8PH UT WOS:000375188703199 ER PT J AU Xu, RJ Wang, K Mileva, I Hannun, YA Obeid, LM Mao, CG AF Xu, Ruijuan Wang, Kai Mileva, Izolda Hannun, Yusuf A. Obeid, Lina M. Mao, Cungui TI Alkaline ceramidase 2 and its bioactive product sphingosine are novel regulators of the DNA damage response SO ONCOTARGET LA English DT Article DE ceramide; Golgi; p53; programmed cell death; reactive oxygen species ID RADIATION-INDUCED APOPTOSIS; INDUCED CELL-DEATH; CANCER-CELLS; MITOCHONDRIAL PATHWAY; CONFERS RESISTANCE; OXIDATIVE STRESS; UP-REGULATION; HELA-CELLS; ACID; SPHINGOSINE-1-PHOSPHATE AB Human cells respond to DNA damage by elevating sphingosine, a bioactive sphingolipid that induces programmed cell death (PCD) in response to various forms of stress, but its regulation and role in the DNA damage response remain obscure. Herein we demonstrate that DNA damage increases sphingosine levels in tumor cells by upregulating alkaline ceramidase 2 (ACER2) and that the upregulation of the ACER2/sphingosine pathway induces PCD in response to DNA damage by increasing the production of reactive oxygen species (ROS). Treatment with the DNA damaging agent doxorubicin increased both ACER2 expression and sphingosine levels in HCT116 cells in a dose-dependent manner. ACER2 overexpression increased sphingosine in HeLa cells whereas knocking down ACER2 inhibited the doxorubicin-induced increase in sphingosine in HCT116 cells, suggesting that DNA damage elevates sphingosine by upregulating ACER2. Knocking down ACER2 inhibited an increase in the apoptotic and necrotic cell population and the cleavage of poly ADP ribose polymerase (PARP) in HCT116 cells in response to doxorubicin as well as doxorubicin-induced release of lactate dehydrogenase (LDH) from these cells. Similar to treatment with doxorubicin, ACER2 overexpression induced an increase in the apoptotic and necrotic cell population and PARP cleavage in HeLa cells and LDH release from cells, suggesting that ACER2 upregulation mediates PCD in response to DNA damage through sphingosine. Mechanistic studies demonstrated that the upregulation of the ACER2/sphingosine pathway induces PCD by increasing ROS levels. Taken together, these results suggest that the ACER2/sphingosine pathway mediates PCD in response to DNA damage through ROS production. C1 [Xu, Ruijuan; Wang, Kai; Hannun, Yusuf A.; Obeid, Lina M.; Mao, Cungui] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Xu, Ruijuan; Wang, Kai; Hannun, Yusuf A.; Obeid, Lina M.; Mao, Cungui] SUNY Stony Brook, Stony Brook Canc Ctr, Stony Brook, NY 11794 USA. [Mileva, Izolda] SUNY Stony Brook, Lipid Core Facil, Stony Brook, NY 11794 USA. [Obeid, Lina M.] Ralph H Johnson Vet Adm Hosp, Stony Brook, NY 11794 USA. RP Mao, CG (reprint author), SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA.; Mao, CG (reprint author), SUNY Stony Brook, Stony Brook Canc Ctr, Stony Brook, NY 11794 USA. EM cungui.mao@stonybrook.edu FU National Institutes of Health Grants [R01CA104834, R01CA163825, P20RR017677, P01CA097132] FX This work was supported, in whole or in part, by National Institutes of Health Grants R01CA104834 (to C.M.), R01CA163825 (to C.M), P20RR017677 (to L.M.O.), and P01CA097132 (to Y.A.H). NR 54 TC 2 Z9 2 U1 1 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 APR 5 PY 2016 VL 7 IS 14 BP 18440 EP 18457 PG 18 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DL5TE UT WOS:000375699000091 PM 26943039 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 RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Downs, John R.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [O'Malley, Patrick G.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Downs, JR (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 4 TC 0 Z9 0 U1 1 U2 3 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 APR 5 PY 2016 VL 164 IS 7 BP 509 EP 510 DI 10.7326/L15-0522 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DI6QP UT WOS:000373625300018 PM 27043985 ER PT J AU Weisbord, SD Palevsky, PM AF Weisbord, Steven D. Palevsky, Paul M. TI Prevention Strategies for Contrast-Induced Nephropathy SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID ASSOCIATION TASK-FORCE; PRACTICE GUIDELINES C1 [Weisbord, Steven D.; Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. OI Palevsky, Paul/0000-0002-7334-5400 NR 5 TC 0 Z9 0 U1 0 U2 1 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 APR 5 PY 2016 VL 164 IS 7 BP 511 EP 511 DI 10.7326/L16-0098 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DI6QP UT WOS:000373625300021 PM 27043990 ER PT J AU Alfredsson, J Stebbins, A Brennan, JM Matsouaka, R Afilalo, J Peterson, ED Vemulapalli, S Rumsfeld, JS Shahian, D Mack, MJ Alexander, KP AF Alfredsson, Joakim Stebbins, Amanda Brennan, J. Matthew Matsouaka, Roland Afilalo, Jonathan Peterson, Eric D. Vemulapalli, Sreekanth Rumsfeld, John S. Shahian, David Mack, Michael J. Alexander, Karen P. TI Gait Speed Predicts 30-Day Mortality After Transcatheter Aortic Valve Replacement Results From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry SO CIRCULATION LA English DT Article DE aged; aortic valve stenosis; heart valve diseases; transcatheter aortic valve replacement ID HIGH-RISK PATIENTS; END-POINT DEFINITIONS; ELDERLY-PATIENTS; CARDIAC-SURGERY; OLDER-ADULTS; CONSENSUS DOCUMENT; MAJOR MORBIDITY; PARTNER TRIAL; FRAILTY; IMPLANTATION AB Background Surgical risk scores do not include frailty assessments (eg, gait speed), which are of particular importance for patients with severe aortic stenosis considering transcatheter aortic valve replacement. Methods and Results We assessed the association of 5-m gait speed with outcomes in a cohort of 8039 patients who underwent transcatheter aortic valve replacement (November 2011-June 2014) and were included in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for Society of Thoracic Surgeons-predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The overall median gait speed was 0.63 m/s (25th-75th percentile, 0.47-0.79 m/s), with the slowest walkers (<0.5 m/s) constituting 28%, slow walkers (0.5-0.83 m/s) making up 48%, and normal walkers (>0.83 m/s) constituting 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively (P<0.001). Each 0.2-m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio, 1.11; 95% confidence interval, 1.01-1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio, 1.35; 95% confidence interval, 1.01-1.80), significantly longer hospital stays, and a lower probability of being discharged to home. Conclusions Gait speed is independently associated with 30-day mortality after transcatheter aortic valve replacement. Identification of frail patients with the slowest gait speeds facilitates preprocedural evaluation and anticipation of a higher level of postprocedural care. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737528. C1 [Alfredsson, Joakim; Stebbins, Amanda; Peterson, Eric D.; Alexander, Karen P.] Duke Clin Res Inst, Room 0311,Terrace Level,2400 Pratt St, Durham, NC 27705 USA. [Alfredsson, Joakim] Linkoping Univ, Dept Cardiol, S-58183 Linkoping, Sweden. [Alfredsson, Joakim] Linkoping Univ, Dept Med & Hlth Sci, S-58183 Linkoping, Sweden. [Brennan, J. Matthew; Matsouaka, Roland; Peterson, Eric D.; Vemulapalli, Sreekanth; Alexander, Karen P.] Duke Univ, Sch Med, Durham, NC USA. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Rumsfeld, John S.] Univ Colorado, Sch Med, Aurora, CO USA. [Shahian, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mack, Michael J.] Baylor Scott & White Hlth, Plano, TX USA. RP Alexander, KP (reprint author), Duke Clin Res Inst, Room 0311,Terrace Level,2400 Pratt St, Durham, NC 27705 USA. EM karen.alexander@duke.edu FU STS/ACC TVT Registry FX This research was supported by the STS/ACC TVT Registry. The views expressed in this article represent those of the authors and do not necessarily represent the official views of the STS/ACC TVT Registry or the views of its associated professional societies, identified at www.STS/ACC TVT Registry.com. NR 39 TC 10 Z9 11 U1 4 U2 5 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 APR 5 PY 2016 VL 133 IS 14 BP 1351 EP 1359 DI 10.1161/CIRCULATIONAHA.115.020279 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DI1ZE UT WOS:000373294700004 PM 26920495 ER PT J AU Siu, AL Bibbins-Domingo, K Grossman, DC Davidson, KW Epling, JW Garcia, FAR Gillman, M Kemper, AR Krist, AH Kurth, AE Landefeld, CS Mangione, CM Harper, DM Phillips, WR Phipps, MG Pignone, MP AF Siu, Albert L. Bibbins-Domingo, Kirsten Grossman, David C. Davidson, Karina W. Epling, John W., Jr. Garcia, Francisco A. R. Gillman, Matthew Kemper, Alex R. Krist, Alex H. Kurth, Ann E. Landefeld, C. Seth Mangione, Carol M. Harper, Diane M. Phillips, William R. Phipps, Maureen G. Pignone, Michael P. CA USPSTF TI Screening for Chronic Obstructive Pulmonary Disease US Preventive Services Task Force Recommendation Statement SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SMOKING-CESSATION; COPD; QUESTIONNAIRE; SPIROMETRY; SMOKERS AB IMPORTANCE About 14% of US adults aged 40 to 79 years have chronic obstructive pulmonary disease (COPD), and it is the third leading cause of death in the United States. Persons with severe COPD are often unable to participate in normal physical activity due to deterioration of lung function. OBJECTIVE To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for COPD in asymptomatic adults. EVIDENCE REVIEW The USPSTF reviewed the evidence on whether screening for COPD in asymptomatic adults (those who do not recognize or report respiratory symptoms) improves health outcomes. The USPSTF reviewed the diagnostic accuracy of screening tools (including prescreening questionnaires and spirometry); whether screening for COPD improves the delivery and uptake of targeted preventive services, such as smoking cessation or relevant immunizations; and the possible harms of screening for and treatment of mild to moderate COPD. FINDINGS Similar to 2008, the USPSTF did not find evidence that screening for COPD in asymptomatic persons improves health-related quality of life, morbidity, or mortality. The USPSTF determined that early detection of COPD, before the development of symptoms, does not alter the course of the disease or improve patient outcomes. The USPSTF concludes with moderate certainty that screening for COPD in asymptomatic persons has no net benefit. CONCLUSIONS AND RECOMMENDATION The USPSTF recommends against screening for COPD in asymptomatic adults. (D recommendation) C1 [Siu, Albert L.] Mt Sinai Sch Med, New York, NY USA. [Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Grossman, David C.] Grp Hlth Res Inst, Seattle, WA USA. [Davidson, Karina W.] Columbia Univ, New York, NY USA. [Epling, John W., Jr.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Garcia, Francisco A. R.] Pima Cty Dept Hlth, Tucson, AZ USA. [Gillman, Matthew] Harvard Univ, Sch Med, Boston, MA USA. [Gillman, Matthew] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Kemper, Alex R.] Duke Univ, Durham, NC USA. [Krist, Alex H.] Fairfax Family Practice, Fairfax, VA USA. [Krist, Alex H.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Kurth, Ann E.] Yale Univ, Sch Nursing, West Haven, CT USA. [Landefeld, C. Seth] Univ Alabama Birmingham, Birmingham, AL USA. [Mangione, Carol M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Harper, Diane M.] Univ Louisville, Louisville, KY 40292 USA. [Phillips, William R.] Univ Washington, Seattle, WA 98195 USA. [Phipps, Maureen G.] Brown Univ, Providence, RI 02912 USA. [Pignone, Michael P.] Univ N Carolina, Chapel Hill, NC USA. RP Siu, AL (reprint author), Mt Sinai Sch Med, New York, NY USA. OI Phillips, William/0000-0003-2802-4349; Epling, John W/0000-0001-9445-8669 NR 18 TC 9 Z9 9 U1 2 U2 4 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 APR 5 PY 2016 VL 315 IS 13 BP 1372 EP 1377 DI 10.1001/jama.2016.2638 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DI3EP UT WOS:000373381500021 ER PT J AU Wong, JC Li, JJ Pavlova, M Chen, S Wu, AP Wu, SL Gao, X AF Wong, Janice C. Li, Junjuan Pavlova, Milena Chen, Shuohua Wu, Aiping Wu, Shouling Gao, Xiang TI Risk factors for probable REM sleep behavior disorder A community-based study SO NEUROLOGY LA English DT Article ID PARKINSONS-DISEASE; OLFACTORY DYSFUNCTION; CIGARETTE-SMOKING; CAFFEINE INTAKE; NEURODEGENERATION; METAANALYSIS; MULTICENTER; POPULATION; TASTE; ASSOCIATION AB Objective:To examine risk factors for REM sleep behavior disorder (RBD) in a large-scale community-based study.Methods:This community-based study included 12,784 Chinese adults (10,556 men and 2,228 women, aged 24 years or older) who were free of Parkinson disease and dementia in 2012. Probable RBD (pRBD) status was determined by a validated questionnaire (Chinese RBD questionnaire-Hong Kong) in 2012. Potential risk factorsincluding age, sex, smoking, socioeconomic status, physical activity, obesity, consumption of tea (surrogate for caffeine intake) and alcohol, serum concentrations of lipids and glucose, and chronic disease statuswere assessed in 2006. Logistic regression was used to calculate odds ratios and 95% confidence intervals and to test differences in prevalence of pRBD across exposures.Results:Prevalence of pRBD was 5.9% in men and 4.1% in women. In the fully adjusted model, risk factors that were significantly associated with a higher risk of having pRBD included lower education level, coal mining and other blue collar occupation, lower physical activity level, diabetes or prediabetes, lower body mass index, head injury, higher low-density lipoprotein level, and chronic olfactory and taste dysfunction. In sensitivity analyses, restricting to pRBD cases with symptom onset within 1 year or excluding coal miners or those with history of head injury generated similar results.Conclusion:We found several potential risk factors for pRBD, including socioeconomic status, head injury, olfactory and taste dysfunction, and various cardiovascular risk factors. Future prospective studies to establish the temporal relationship between these potential risk factors and RBD are warranted. C1 [Wong, Janice C.; Pavlova, Milena] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. [Wong, Janice C.; Pavlova, Milena] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wong, Janice C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Li, Junjuan; Chen, Shuohua; Wu, Aiping; Wu, Shouling] Hebei United Univ, Dept Internal Med, Kailuan Hosp, Tangshan, Peoples R China. [Gao, Xiang] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. RP Wu, SL (reprint author), Hebei United Univ, Dept Internal Med, Kailuan Hosp, Tangshan, Peoples R China.; Gao, X (reprint author), Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. EM drwusl@163.com; xxg14@psu.edu FU NIH [R21 NS087235-01A1] FX This study was supported by a grant (R21 NS087235-01A1) from the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 38 TC 2 Z9 3 U1 5 U2 9 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 APR 5 PY 2016 VL 86 IS 14 BP 1306 EP 1312 DI 10.1212/WNL.0000000000002414 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DI1YE UT WOS:000373292100007 PM 26819459 ER PT J AU Spartano, NL Himali, JJ Beiser, AS Lewis, GD DeCarli, C Vasan, RS Seshadri, S AF Spartano, Nicole L. Himali, Jayandra J. Beiser, Alexa S. Lewis, Gregory D. DeCarli, Charles Vasan, Ramachandran S. Seshadri, Sudha TI Midlife exercise blood pressure, heart rate, and fitness relate to brain volume 2 decades later SO NEUROLOGY LA English DT Article ID WHITE-MATTER HYPERINTENSITIES; CARDIORESPIRATORY FITNESS; ARTERIAL STIFFNESS; CARDIOVASCULAR-DISEASE; COGNITIVE FUNCTION; ALZHEIMER-DISEASE; PHYSICAL-FITNESS; ASSOCIATION; RISK; MEN AB Objective:To determine whether poor cardiovascular (CV) fitness and exaggerated exercise blood pressure (BP) and heart rate (HR) were associated with worse brain morphology in later life.Methods:Framingham Offspring participants (n = 1,094, 53.9% female) free from dementia and CV disease (CVD) underwent an exercise treadmill test at a mean age of 40 9 years. A second treadmill test and MRI scans of the brain were administered 2 decades later at mean age of 58 8 years.Results:Poor CV fitness and greater diastolic BP and HR response to exercise at baseline were associated with a smaller total cerebral brain volume (TCBV) almost 2 decades later (all p < 0.05) in multivariable adjusted models; the effect of 1 SD lower fitness was equivalent to approximately 1 additional year of brain aging in individuals free of CVD. In participants with prehypertension or hypertension at baseline, exercise systolic BP was also associated with smaller TCBV (p < 0.05).Conclusion:Our results suggest that lower CV fitness and exaggerated exercise BP and HR responses in middle-aged adults are associated with smaller brain volume nearly 2 decades later. Promotion of midlife CV fitness may be an important step towards ensuring healthy brain aging. C1 [Spartano, Nicole L.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02215 USA. [Spartano, Nicole L.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. [Himali, Jayandra J.; Beiser, Alexa S.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Spartano, Nicole L.; Himali, Jayandra J.; Beiser, Alexa S.; Vasan, Ramachandran S.; Seshadri, Sudha] Boston Univ, Sch Publ Hlth, Framingham Heart Study, Boston, MA 02215 USA. [Beiser, Alexa S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Lewis, Gregory D.] Harvard Univ, Med Sch, Massachusetts Gen Hosp, Div Cardiol, Cambridge, MA 02138 USA. [Lewis, Gregory D.] Harvard Univ, Med Sch, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Cambridge, MA 02138 USA. [Lewis, Gregory D.] Broad Inst MIT & Harvard, Cambridge, MA USA. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Davis, CA USA. [DeCarli, Charles] Univ Calif Davis, Ctr Neurosci, Davis, CA USA. RP Spartano, NL (reprint author), Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02215 USA.; Spartano, NL (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA.; Spartano, NL (reprint author), Boston Univ, Sch Publ Hlth, Framingham Heart Study, Boston, MA 02215 USA. EM spartano@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Beiser, Alexa/0000-0001-8551-7778; /0000-0003-1391-9481 FU Framingham Heart Study's National Heart, Lung and Blood Institute [HHSN268201500001I]; NIH [R01-AG047645, R01-AG008122, R01-NS017950, T32-HL07224]; American Heart Association [15GPSGC24800006] FX Supported by the Framingham Heart Study's National Heart, Lung and Blood Institute contract (HHSN268201500001I) with additional support from the following NIH grants (R01-AG047645, R01-AG008122, R01-NS017950, T32-HL07224) and an American Heart Association award (15GPSGC24800006). NR 39 TC 0 Z9 0 U1 3 U2 10 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 APR 5 PY 2016 VL 86 IS 14 BP 1313 EP 1319 DI 10.1212/WNL.0000000000002415 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DI1YE UT WOS:000373292100008 PM 26865519 ER PT J AU Hillebrand, A Tewarie, P van Dellen, E Yu, MC Carbo, EWS Douw, L Gouw, AA van Straaten, ECW Stam, CJ AF Hillebrand, Arjan Tewarie, Prejaas van Dellen, Edwin Yu, Meichen Carbo, Ellen W. S. Douw, Linda Gouw, Alida A. van Straaten, Elisabeth C. W. Stam, Cornelis J. TI Direction of information flow in large-scale resting-state networks is frequency-dependent SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE information flow; phase transfer entropy; resting-state networks; magnetoencephalography; atlas-based beamforming ID PHASE-LAG INDEX; FUNCTIONAL CONNECTIVITY; HUMAN BRAIN; MULTIPLE-SCLEROSIS; NEURONAL SYNCHRONY; GAMMA OSCILLATIONS; CELL ASSEMBLIES; MEG; EEG; CORTEX AB Normal brain function requires interactions between spatially separated, and functionally specialized, macroscopic regions, yet the directionality of these interactions in large-scale functional networks is unknown. Magnetoencephalography was used to determine the directionality of these interactions, where directionality was inferred from time series of beamformer-reconstructed estimates of neuronal activation, using a recently proposed measure of phase transfer entropy. We observed well-organized posterior-to-anterior patterns of information flow in the higher-frequency bands (alpha1, alpha2, and beta band), dominated by regions in the visual cortex and posterior default mode network. Opposite patterns of anterior-to-posterior flow were found in the theta band, involving mainly regions in the frontal lobe that were sending information to a more distributed network. Many strong information senders in the theta band were also frequent receivers in the alpha2 band, and vice versa. Our results provide evidence that large-scale resting-state patterns of information flow in the human brain form frequency-dependent reentry loops that are dominated by flow from parieto-occipital cortex to integrative frontal areas in the higher-frequency bands, which is mirrored by a theta band anterior-to-posterior flow. C1 [Hillebrand, Arjan; Tewarie, Prejaas; van Dellen, Edwin; Yu, Meichen; Gouw, Alida A.; van Straaten, Elisabeth C. W.; Stam, Cornelis J.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Neurophysiol, NL-1081 HV Amsterdam, Netherlands. [Hillebrand, Arjan; Tewarie, Prejaas; van Dellen, Edwin; Yu, Meichen; Gouw, Alida A.; van Straaten, Elisabeth C. W.; Stam, Cornelis J.] Vrije Univ Amsterdam, Med Ctr, Magnetoencephalog Ctr, NL-1081 HV Amsterdam, Netherlands. [van Dellen, Edwin] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3508 GA Utrecht, Netherlands. [Carbo, Ellen W. S.; Douw, Linda] Vrije Univ Amsterdam, Med Ctr, Dept Anat & Neurosci, NL-1081 HV Amsterdam, Netherlands. [Douw, Linda] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Gouw, Alida A.] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, NL-1081 HV Amsterdam, Netherlands. [Gouw, Alida A.] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, NL-1081 HV Amsterdam, Netherlands. [van Straaten, Elisabeth C. W.] Nutricia Res, Nutricia Adv Med Nutr, NL-3584 CT Utrecht, Netherlands. RP Hillebrand, A (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Clin Neurophysiol, NL-1081 HV Amsterdam, Netherlands.; Hillebrand, A (reprint author), Vrije Univ Amsterdam, Med Ctr, Magnetoencephalog Ctr, NL-1081 HV Amsterdam, Netherlands. EM a.hillebrand@vumc.nl FU Dutch MS Research Foundation [09-358d] FX We thank Nico Akemann, Ndedi Sijsma, Karin Plugge, Marlous van den Hoek, and Peter-Jan Ris for the MEG acquisitions, as well as the three anonymous reviewers for their constructive comments during the preparation of this manuscript. This work was supported by a private sponsorship to the VUmc MS Center Amsterdam. The MS Center is sponsored through a program grant by the Dutch MS Research Foundation (Grant 09-358d). NR 89 TC 9 Z9 9 U1 8 U2 24 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 APR 5 PY 2016 VL 113 IS 14 BP 3867 EP 3872 DI 10.1073/pnas.1515657113 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI2UI UT WOS:000373354000055 PM 27001844 ER PT J AU Chekroud, AM Ward, EJ Rosenberg, MD Holmes, AJ AF Chekroud, Adam M. Ward, Emily J. Rosenberg, Monica D. Holmes, Avram J. TI Patterns in the human brain mosaic discriminate males from females SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter C1 [Chekroud, Adam M.; Ward, Emily J.; Rosenberg, Monica D.; Holmes, Avram J.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Holmes, Avram J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Chekroud, AM (reprint author), Yale Univ, Dept Psychol, New Haven, CT 06520 USA. EM adam.chekroud@yale.edu OI Chekroud, Adam/0000-0002-0497-596X NR 5 TC 6 Z9 6 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 5 PY 2016 VL 113 IS 14 BP E1968 EP E1968 DI 10.1073/pnas.1523888113 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI2UI UT WOS:000373354000003 PM 26984491 ER PT J AU Huber, BR Meabon, JS Hoffer, ZS Zhang, J Hoekstra, JG Pagulayan, KF McMillan, PJ Mayer, CL Banks, WA Kraemer, BC Raskind, MA McGavern, DB Peskind, ER Cook, DG AF Huber, B. R. Meabon, J. S. Hoffer, Z. S. Zhang, J. Hoekstra, J. G. Pagulayan, K. F. McMillan, P. J. Mayer, C. L. Banks, W. A. Kraemer, B. C. Raskind, M. A. McGavern, D. B. Peskind, E. R. Cook, D. G. TI BLAST EXPOSURE CAUSES DYNAMIC MICROGLIAL/MACROPHAGE RESPONSES AND MICRODOMAINS OF BRAIN MICROVESSEL DYSFUNCTION SO NEUROSCIENCE LA English DT Article DE blood-brain barrier; two-photon microscopy; neuropathology; microglia; macrophages ID CHRONIC TRAUMATIC ENCEPHALOPATHY; IN-VIVO; MICROGLIAL ACTIVATION; WHITE-MATTER; MOUSE MODEL; INJURY; BLOOD; BARRIER; CORTEX; IMPACT AB Exposure to blast overpressure (BOP) is associated with behavioral, cognitive, and neuroimaging abnormalities. We investigated the dynamic responses of cortical vasculature and its relation to microglia/macrophage activation in mice using intravital two-photon microscopy following mild blast exposure. We found that blast caused vascular dysfunction evidenced by microdomains of aberrant vascular permeability. Microglial/macrophage activation was specifically associated with these restricted microdomains, as evidenced by rapid microglial process retraction, increased ameboid morphology, and escape of blood-borne Q-dot tracers that were internalized in microglial/macrophage cell bodies and phagosome-like compartments. Microdomains of cortical vascular disruption and microglial/macrophage activation were also associated with aberrant tight junction morphology that was more prominent after repetitive (3 x) blast exposure. Repetitive, but not single, BOPs also caused TNF alpha elevation two weeks post-blast. In addition, following a single BOP we found that aberrantly phosphorylated tau rapidly accumulated in perivascular domains, but cleared within four hours, suggesting it was removed from the perivascular area, degraded, and/or dephosphorylated. Taken together these findings argue that mild blast exposure causes an evolving CNS insult that is initiated by discrete disturbances of vascular function, thereby setting the stage for more protracted and more widespread neuro-inflammatory responses. Published by Elsevier Ltd. on behalf of IBRO. C1 [Huber, B. R.] Boston Univ, VA Jamaica Plain, Dept Neurol, Sch Med, Jamaica Plain, MA USA. [Meabon, J. S.; Pagulayan, K. F.; McMillan, P. J.; Mayer, C. L.; Raskind, M. A.; Peskind, E. R.] VA Puget Sound Healthcare Syst, Northwest Network Mental Illness Res Educ & Clin, Seattle, WA USA. [Meabon, J. S.; Pagulayan, K. F.; McMillan, P. J.; Mayer, C. L.; Raskind, M. A.; Peskind, E. R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. [Hoffer, Z. S.] US Army, Madigan Army Med Ctr, Joint Base Lewis Mcchord, WA USA. [Zhang, J.; Hoekstra, J. G.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98108 USA. [Banks, W. A.; Kraemer, B. C.; Cook, D. G.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Banks, W. A.; Kraemer, B. C.; Cook, D. G.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98108 USA. [McGavern, D. B.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Cook, D. G.] Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98108 USA. RP Cook, DG (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, 1660 South Columbian Way, Seattle, WA 98108 USA. EM dgcook@u.washington.edu OI Hoekstra, Jake/0000-0001-6597-5878 FU Department of Veterans Affairs Office of Research and Development Medical Research Service; VA Rehabilitation Research and Development Service; University of Washington Royalty Research Fund [R01AG046619]; Northwest Network Mental Illness Research, Education and Clinical Center; Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs; NIH [T32 AG000258]; VA CSR&D Career Development Award [IK2 CX00516] FX This work was supported by the Department of Veterans Affairs Office of Research and Development Medical Research Service (D.G.C., B.C.K.), VA Rehabilitation Research and Development Service (E.R.P.), University of Washington Royalty Research Fund (D.G.C.); R01AG046619 (W.A.B.); Northwest Network Mental Illness Research, Education and Clinical Center (E.R.P., B.R.H., J.S.M., K.F.P., P.J.M., C.L.M.), Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs (B.R.H.); NIH T32 AG000258 (J.S.M.), VA CSR&D Career Development Award Program #IK2 CX00516 (K.F.P.). We thank Dr. Gerard Schellenberg (Univ. Pennsylvania) for providing Tau knock-out samples. NR 41 TC 2 Z9 2 U1 2 U2 15 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 APR 5 PY 2016 VL 319 BP 206 EP 220 DI 10.1016/j.neuroscience.2016.01.022 PG 15 WC Neurosciences SC Neurosciences & Neurology GA DD9RD UT WOS:000370262400019 PM 26777891 ER PT J AU Bonilla, C Lewis, SJ Martin, RM Donovan, JL Hamdy, FC Neal, DE Eeles, R Easton, D Kote-Jarai, Z Al Olama, AA Benlloch, S Muir, K Giles, GG Wiklund, F Gronberg, H Haiman, CA Schleutker, J Nordestgaard, BG Travis, RC Pashayan, N Khaw, KT Stanford, JL Blot, WJ Thibodeau, S Maier, C Kibel, AS Cybulski, C Cannon-Albright, L Brenner, H Park, J Kaneva, R Batra, J Teixeira, MR Pandha, H Lathrop, M Smith, GD AF Bonilla, Carolina Lewis, Sarah J. Martin, Richard M. Donovan, Jenny L. Hamdy, Freddie C. Neal, David E. Eeles, Rosalind Easton, Doug Kote-Jarai, Zsofia Al Olama, Ali Amin Benlloch, Sara Muir, Kenneth Giles, Graham G. Wiklund, Fredrik Gronberg, Henrik Haiman, Christopher A. Schleutker, Johanna Nordestgaard, Borge G. Travis, Ruth C. Pashayan, Nora Khaw, Kay-Tee Stanford, Janet L. Blot, William J. Thibodeau, Stephen Maier, Christiane Kibel, Adams S. Cybulski, Cezary Cannon-Albright, Lisa Brenner, Hermann Park, Jong Kaneva, Radka Batra, Jyotsna Teixeira, Manuel R. Pandha, Hardev Lathrop, Mark Smith, George Davey CA PRACTICAL Consortium TI Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort SO BMC MEDICINE LA English DT Article DE Boys; Mendelian randomization; Prostate cancer; Puberty; Tanner scale ID GROWTH-FACTOR-I; GENOME-WIDE ASSOCIATION; BODY-SIZE; AGE; MENARCHE; METAANALYSIS; HEIGHT; LOCI; VARIANTS; PROTECT AB Background: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach. Methods: We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a replication sample. Results: In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high-vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade. Conclusions: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease. C1 [Bonilla, Carolina; Lewis, Sarah J.; Martin, Richard M.; Donovan, Jenny L.; Smith, George Davey] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Bonilla, Carolina; Lewis, Sarah J.; Martin, Richard M.; Smith, George Davey] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England. [Martin, Richard M.] Natl Inst Hlth Res, Bristol Biomed Res Unit Nutr, Bristol, Avon, England. [Hamdy, Freddie C.; Neal, David E.] Univ Oxford, Nuffield Dept Surg, Oxford, England. [Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Surg Oncol Urooncol S4, Box 279,Hills Rd, Cambridge CB2 2QQ, England. [Eeles, Rosalind; Kote-Jarai, Zsofia] Inst Canc Res, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Fulham, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Fulham, Surrey, England. [Easton, Doug; Al Olama, Ali Amin; Benlloch, Sara] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge, England. [Muir, Kenneth] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester M13 9PL, Lancs, England. [Giles, Graham G.] Canc Council Victoria, 615 St Kilda Rd, Melbourne, Vic 3004, Australia. [Giles, Graham G.] Univ Melbourne, Ctr Biostat & Epidemiol, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia. [Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Schleutker, Johanna] Univ Turku, Dept Med Biochem & Genet, Turku, Finland. [Schleutker, Johanna] Univ Tampere, Inst Biomed Technol BioMediTech, FIN-33101 Tampere, Finland. [Schleutker, Johanna] FimLab Labs, Tampere, Finland. [Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev Ringvej 75, DK-2730 Herlev, Denmark. [Travis, Ruth C.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Pashayan, Nora] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge, England. [Pashayan, Nora] UCL, Dept Appl Hlth Res, 1-19 Torrington Pl, London WC1E 7HB, England. [Khaw, Kay-Tee] Univ Cambridge, Cambridge Inst Publ Hlth, Forvie Site,Robinson Way, Cambridge CB2 0SR, England. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Blot, William J.] Int Epidemiol Inst, 1455 Res Blvd,Suite 550, Rockville, MD 20850 USA. [Thibodeau, Stephen] Mayo Clin, Rochester, MN USA. [Maier, Christiane] Univ Hosp Ulm, Dept Urol, Ulm, Germany. [Maier, Christiane] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany. [Kibel, Adams S.] Brigham & Womens Hosp, Dana Farber Canc Inst, 45 Francis St,ASB 2-3, Boston, MA 02115 USA. [Kibel, Adams S.] Washington Univ, St Louis, MO USA. [Cybulski, Cezary] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [Cannon-Albright, Lisa] Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany. [Park, Jong] Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Prevent & Control, 12902 Magnolia Dr, Tampa, FL 33682 USA. [Kaneva, Radka] Med Univ Sofia, Mol Med Ctr, 2 Zdrave St, Sofia 1431, Bulgaria. [Kaneva, Radka] Med Univ Sofia, Dept Med Chem & Biochem, 2 Zdrave St, Sofia 1431, Bulgaria. [Batra, Jyotsna] Queensland Univ Technol, Australian Prostate Canc Res Ctr Qld, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Batra, Jyotsna] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld 4001, Australia. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Pandha, Hardev] Univ Surrey, Guildford GU2 7XH, Surrey, England. [Lathrop, Mark] Ctr Natl Genotypage, Energie Atom, Evry, France. [Lathrop, Mark] McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ, Canada. RP Martin, RM (reprint author), Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.; Martin, RM (reprint author), Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.; Martin, RM (reprint author), Natl Inst Hlth Res, Bristol Biomed Res Unit Nutr, Bristol, Avon, England. EM richard.martin@bristol.ac.uk RI Batra, Jyotsna/B-4130-2011; Henrique, Rui/I-2757-2013; Davey Smith, George/A-7407-2013; Brenner, Hermann/B-4627-2017; OI Henrique, Rui/0000-0003-3171-4666; Davey Smith, George/0000-0002-1407-8314; Brenner, Hermann/0000-0002-6129-1572; Bonilla, Carolina/0000-0002-9972-6383; Lewis, Sarah/0000-0003-4311-6890; Clements, Judith/0000-0001-6026-1964 FU World Cancer Research Fund [2011/419]; Cancer Research UK [C18281/A19169, C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565]; MRC; University of Bristol [G0600705, MC_UU_12013/19]; Cancer Research UK programme grant [C18281/A19169]; NIHR; University Hospitals Bristol NHS Foundation Trust; UK NIHR Health Technology Assessment (HTA) Programme [HTA 96/20/99, ISRCTN20141297]; European Community [223175 (HEALTH-F2-2009-223175) (COGS)]; National Institutes of Health [CA128978]; Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; Royal Marsden NHS Foundation Trust; University of Bristol FX This work was supported by the World Cancer Research Fund (2011/419) and Cancer Research UK (C18281/A19169). The Integrative Epidemiology Unit (IEU) is supported by the MRC and the University of Bristol (G0600705, MC_UU_12013/19), and the Integrative Cancer Epidemiology Programme is supported by Cancer Research UK programme grant C18281/A19169. The National Institute for Health Research (NIHR) Bristol Nutrition Biomedical Research Unit is funded by the NIHR and is a partnership between University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The ProtecT study is supported by the UK NIHR Health Technology Assessment (HTA) Programme (HTA 96/20/99; ISRCTN20141297). Funding for PRACTICAL and the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. We acknowledge support from the NIHR to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. NR 38 TC 1 Z9 1 U1 3 U2 14 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 APR 4 PY 2016 VL 14 AR 66 DI 10.1186/s12916-016-0602-x PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DI3YU UT WOS:000373437600001 PM 27044414 ER PT J AU Hiemenz, MC Kadauke, S Lieberman, DB Roth, DB Zhao, JH Watt, CD Daber, RD Morrissette, JJD AF Hiemenz, Matthew C. Kadauke, Stephan Lieberman, David B. Roth, David B. Zhao, Jianhua Watt, Christopher D. Daber, Robert D. Morrissette, Jennifer J. D. TI Building a Robust Tumor Profiling Program: Synergy between Next-Generation Sequencing and Targeted Single-Gene Testing SO PLOS ONE LA English DT Article ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; KRAS MUTATIONS; RARE MUTATIONS; VALIDATION; SPECIMENS; PARALLEL; ERLOTINIB; RESISTANCE; THERAPIES AB Next-generation sequencing (NGS) is a powerful platform for identifying cancer mutations. Routine clinical adoption of NGS requires optimized quality control metrics to ensure accurate results. To assess the robustness of our clinical NGS pipeline, we analyzed the results of 304 solid tumor and hematologic malignancy specimens tested simultaneously by NGS and one or more targeted single-gene tests (EGFR, KRAS, BRAF, NPM1, FLT3, and JAK2). For samples that passed our validated tumor percentage and DNA quality and quantity thresholds, there was perfect concordance between NGS and targeted single-gene tests with the exception of two FLT3 internal tandem duplications that fell below the stringent preestablished reporting threshold but were readily detected by manual inspection. In addition, NGS identified clinically significant mutations not covered by single-gene tests. These findings confirm NGS as a reliable platform for routine clinical use when appropriate quality control metrics, such as tumor percentage and DNA quality cutoffs, are in place. Based on our findings, we suggest a simple workflow that should facilitate adoption of clinical oncologic NGS services at other institutions. C1 [Hiemenz, Matthew C.; Lieberman, David B.; Roth, David B.; Zhao, Jianhua; Watt, Christopher D.; Daber, Robert D.; Morrissette, Jennifer J. D.] Hosp Univ Penn, Dept Pathol & Lab Med, Ctr Personalized Diagnost, 3400 Spruce St, Philadelphia, PA 19104 USA. [Kadauke, Stephan] Univ Penn, Perelman Sch Med, Med Scientist Training Program, Philadelphia, PA USA. [Hiemenz, Matthew C.; Daber, Robert D.] BioReference Labs, Elmwood Pk, NJ USA. [Kadauke, Stephan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Morrissette, JJD (reprint author), Hosp Univ Penn, Dept Pathol & Lab Med, Ctr Personalized Diagnost, 3400 Spruce St, Philadelphia, PA 19104 USA. EM Jennifer.Morrissette@uphs.upenn.edu NR 44 TC 1 Z9 1 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 4 PY 2016 VL 11 IS 4 AR e0152851 DI 10.1371/journal.pone.0152851 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI6EN UT WOS:000373592100038 PM 27043212 ER PT J AU Yetish, G Kaplan, H Gurven, M Wood, B Pontzer, H Manger, PR Wilson, C McGregor, R Siegel, JM AF Yetish, Gandhi Kaplan, Hillard Gurven, Michael Wood, Brian Pontzer, Herman Manger, Paul R. Wilson, Charles McGregor, Ronald Siegel, Jerome M. TI Ancestral sleep Response SO CURRENT BIOLOGY LA English DT Letter C1 [Yetish, Gandhi; Kaplan, Hillard] Univ New Mexico, Dept Anthropol, MSC01-1040, Albuquerque, NM 87131 USA. [Gurven, Michael] Univ Calif Santa Barbara, Dept Anthropol, 1210 Cheadle Hall, Santa Barbara, CA 93106 USA. [Wood, Brian] Yale Univ, Dept Anthropol, 10 Sachem St, New Haven, CT 06511 USA. [Pontzer, Herman] CUNY Hunter Coll, Dept Anthropol, 695 Pk Ave, New York, NY 10065 USA. [Manger, Paul R.] Univ Witwatersrand, Sch Anat Sci, 7 York Rd, ZA-2193 Johannesburg, South Africa. [Wilson, Charles] Univ Calif Los Angeles, Dept Neurol, 10833 Conte Ave, Los Angeles, CA 90095 USA. [Wilson, Charles; Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, 10833 Conte Ave, Los Angeles, CA 90095 USA. [McGregor, Ronald; Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Siegel, Jerome M.] VA Greater Angeles Healthcare Syst, 16111 Plummer St, Los Angeles, CA 91343 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Brain Res Inst, 10833 Conte Ave, Los Angeles, CA 90095 USA.; Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.; Siegel, JM (reprint author), VA Greater Angeles Healthcare Syst, 16111 Plummer St, Los Angeles, CA 91343 USA. EM jsiegel@ucla.edu NR 10 TC 0 Z9 0 U1 5 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD APR 4 PY 2016 VL 26 IS 7 BP R273 EP R274 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DI1RP UT WOS:000373273600008 PM 27046810 ER PT J AU Brooks, BL Iverson, GL Atkins, JE Zafonte, R Berkner, PD AF Brooks, Brian L. Iverson, Grant L. Atkins, Joseph E. Zafonte, Ross Berkner, Paul D. TI Sex Differences and Self-Reported Attention Problems During Baseline Concussion Testing SO APPLIED NEUROPSYCHOLOGY-CHILD LA English DT Article DE adolescents; baseline; children; gender; return to play; TBI ID SPORTS-RELATED CONCUSSION; DEFICIT HYPERACTIVITY DISORDER; HIGH-SCHOOL; NEUROCOGNITIVE PERFORMANCE; INTERNATIONAL-CONFERENCE; CONSENSUS STATEMENT; CLINICAL ARTICLE; SOCCER PLAYERS; SYMPTOMS; RECOVERY AB Amateur athletic programs often use computerized cognitive testing as part of their concussion management programs. There is evidence that athletes with preexisting attention problems will have worse cognitive performance and more symptoms at baseline testing. The purpose of this study was to examine whether attention problems affect assessments differently for male and female athletes. Participants were drawn from a database that included 6,840 adolescents from Maine who completed Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) at baseline (primary outcome measure). The final sample included 249 boys and 100 girls with self-reported attention problems. Each participant was individually matched for sex, age, number of past concussions, and sport to a control participant (249 boys, 100 girls). Boys with attention problems had worse reaction time than boys without attention problems. Girls with attention problems had worse visual-motor speed than girls without attention problems. Boys with attention problems reported more total symptoms, including more cognitive-sensory and sleep-arousal symptoms, compared with boys without attention problems. Girls with attention problems reported more cognitive-sensory, sleep-arousal, and affective symptoms than girls without attention problems. When considering the assessment, management, and outcome from concussions in adolescent athletes, it is important to consider both sex and preinjury attention problems regarding cognitive test results and symptom reporting. C1 [Brooks, Brian L.] Alberta Childrens Prov Gen Hosp, Neurosci Program Brain Injury & Rehabil, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada. [Brooks, Brian L.] Univ Calgary, Dept Pediat, Cumming Sch Med, Calgary, AB T2N 1N4, Canada. [Brooks, Brian L.] Univ Calgary, Cumming Sch Med, Dept Clin Neurosci, Calgary, AB, Canada. [Brooks, Brian L.] Univ Calgary, Alberta Childrens Hosp Res Inst, Calgary, AB, Canada. [Iverson, Grant L.] Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Dept Phys Med & Rehabil,MassGen Hosp Children Spo, Boston, MA USA. [Iverson, Grant L.; Zafonte, Ross] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.; Zafonte, Ross] Massachusetts Gen Hosp Home Base Program, Boston, MA USA. [Atkins, Joseph E.] Colby Coll, Dept Psychol, Waterville, ME 04901 USA. [Zafonte, Ross] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Spaulding Rehabil Hosp,Sch Med,Dept Phys Med & Re, Boston, MA 02115 USA. [Berkner, Paul D.] Colby Coll, Hlth Serv, Waterville, ME 04901 USA. [Berkner, Paul D.] Colby Coll, Dept Biol, Waterville, ME 04901 USA. RP Brooks, BL (reprint author), Alberta Childrens Prov Gen Hosp, Neurosci Program, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada. EM brian.brooks@albertahealthservices.ca FU Goldfarb Center for Public Policy and Civic Engagement/Colby College; Bill and Joan Alfond Foundation; Harvard Integrated Program to Protect and Improve the Health of National Football League Players Association Members; Mooney-Reed Charitable Foundation FX This work was funded in part by the Goldfarb Center for Public Policy and Civic Engagement/Colby College and the Bill and Joan Alfond Foundation. RZ was supported in part by the Harvard Integrated Program to Protect and Improve the Health of National Football League Players Association Members. GLI and RZ acknowledge support from the Mooney-Reed Charitable Foundation. NR 44 TC 2 Z9 2 U1 3 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 2162-2965 EI 2162-2973 J9 APPL NEUROPSYCH-CHIL JI Appl. Neuropsychol.-Child PD APR 2 PY 2016 VL 5 IS 2 BP 119 EP 126 DI 10.1080/21622965.2014.1003066 PG 8 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA DJ1BG UT WOS:000373937500005 PM 25923339 ER PT J AU Braquehais, MD Eiroa-Orosa, FJ Holmes, KM Lusilla, P Bravo, M Mozo, X Mezzatesta, M Casanovas, M Pujol, T Sher, L AF Dolores Braquehais, Maria Eiroa-Orosa, Francisco Jose Holmes, Kristin M. Lusilla, Pilar Bravo, Maria Mozo, Xulian Mezzatesta, Marcela Casanovas, Marta Pujol, Tania Sher, Leo TI Differences in Physicians' and Nurses' Recent Suicide Attempts: An Exploratory Study SO ARCHIVES OF SUICIDE RESEARCH LA English DT Article DE suicide attempts; nurses; physicians ID DOCTORS; RISK; DEPRESSION; IDEATION; GENDER; RATES AB The aim of this study was to examine the characteristics of physicians' and nurses' suicide attempts (SA). A retrospective review of 493 medical records of physicians and nurses admitted to an inpatient unit for health professionals; 36 patients had a recent SA. Depression, cluster B and C personality disorders, and a history of previous SA were more prevalent in patients with a recent SA compared to those without it. Both professional groups preferred drug overdose as a suicide method. Physicians made more lethal attempts and had a history of more previous stressors than nurses. Depression, cluster B and C personality disorders, and previous SA should be appropriately screened and treated in order to prevent SA amongst physicians and nurses. C1 [Dolores Braquehais, Maria; Bravo, Maria; Mozo, Xulian; Pujol, Tania] Generalitat Catalonia, Dept Hlth, Galatea Clin, Integral Care Program Sick Hlth Care Profess, Barcelona, Spain. [Dolores Braquehais, Maria; Bravo, Maria; Mozo, Xulian; Pujol, Tania] Coll Metges Barcelona, Galatea Fdn, Barcelona, Spain. [Dolores Braquehais, Maria; Lusilla, Pilar] Univ Autonoma Barcelona, CIBERSAM, Vall dHebron Univ Hosp, Dept Psychiat & Legal Med, E-08193 Barcelona, Spain. [Eiroa-Orosa, Francisco Jose] Univ E London, Sch Psychol, Water Lane, Stratford, England. [Holmes, Kristin M.; Sher, Leo] James J Peters Vet Adm Med Ctr, Dept Psychiat, New York, NY USA. [Holmes, Kristin M.; Sher, Leo] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Mezzatesta, Marcela] Fundacio Salut & Comunitat, Fundacio Orienta, Child & Adolescent Mental Hlth Unit, Barcelona, Spain. [Casanovas, Marta] Univ London Imperial Coll Sci Technol & Med, Ctr Mental Hlth, Hammersmith Hosp Campus, London, England. RP Braquehais, MD (reprint author), Galatea Fdn, Integral Care Program Sick Hlth Care Profess, Inpatient Psychiat Unit Hlth Profess, Galatea Clin, Passeig Bonanova 47, Barcelona 08017, Spain. EM mdbraquehais.paimm@comb.cat RI Eiroa Orosa, Francisco Jose/D-2510-2012 OI Eiroa Orosa, Francisco Jose/0000-0002-4163-6545 NR 17 TC 0 Z9 0 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1381-1118 EI 1543-6136 J9 ARCH SUICIDE RES JI Arch. Suicide Res. PD APR 2 PY 2016 VL 20 IS 2 BP 273 EP 279 DI 10.1080/13811118.2014.996693 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ0PG UT WOS:000373905800013 PM 25517040 ER PT J AU Simmons, L Leavitt, L Ray, A Fosburgh, B Sepucha, K AF Simmons, Leigh Leavitt, Lauren Ray, Alaka Fosburgh, Blair Sepucha, Karen TI Shared Decision Making in Common Chronic Conditions: Impact of a Resident Training Workshop SO TEACHING AND LEARNING IN MEDICINE LA English DT Article DE depression; risk communication; shared decision making; diabetes; resident education ID CLUSTER RANDOMIZED-TRIAL; CARE; IMPLEMENTATION; PHYSICIANS; CLINICIAN AB Problem: Physicians must be competent in several different kinds of communication skills in order to implement shared decision making; however, these skills are not part of routine medical student education, nor are they formally taught during residency training. Intervention: We developed a 1- and 2-hour workshop curriculum for internal medicine residents to promote shared decision making in treatment decisions for four common chronic conditions: diabetes, depression, hypertension, and hyperlipidemia. The workshops included a written case exercise, a short didactic presentation on shared decision-making concepts and strategies for risk communication, and two role-playing exercises focused on decision making for depression and hyperlipidemia treatment. Context: We delivered the workshop as a required component of the resident curriculum in ambulatory medicine. To evaluate the impact of the workshop, we used written course evaluations, tracked the use of the newly introduced Decision Worksheets, and asked preceptors to perform direct observation of treatment decision conversations. Outcome: Residents were involved in the development of the workshop and helped identify key content, suggested framing for difficult topics, and confirmed the need for the skills workshop. One hundred thirty internal medicine and medicine-pediatrics residents attended 8 workshops over a 4-month period. In written cases completed before the workshop, the majority of residents indicated that they would discuss medications, but few mentioned other treatment options or documented patients' goals and preferences in a sample encounter note with a patient with new depression symptoms. Overall, most participants (89.7%) rated the workshop as excellent or very good, and 93.5% said that they would change their practice based on what they learned. Decision Worksheets addressing diabetes, depression, hyperlipidemia, and hypertension were available on a primary care-focused intranet site and were downloaded almost 1,200times in the first 8 months following the workshops. Preceptors were able to observe only one consult during which one of the four topics was discussed. Lessons Learned: Internal medicine residents had considerable gaps in shared decision-making skills as measured in a baseline written exercise. Residents provided valuable contributions to the development of a Decision Worksheet to be used at the point of care. Participants rated the skills workshop highly, though interns rated the exercise more useful than PGY-2 and PGY-3 residents did. The Decision Worksheets were accessed often following the sessions; however, observing the Decision Worksheets in use in real time was a challenge in the resident-faculty clinic. Additional studies are warranted to examine whether the workshop was successful in increasing residents' ability to implement skills in practice. C1 [Simmons, Leigh; Leavitt, Lauren; Ray, Alaka; Fosburgh, Blair; Sepucha, Karen] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Simmons, L (reprint author), Hlth Decis Sci Ctr, 50 Staniford St,Suite 802, Boston, MA 02114 USA. EM lhsimmons@partners.org FU Picker Institute; Arnold P. Gold Foundation FX This work was supported by grant funding from the Picker Institute and the Arnold P. Gold Foundation. NR 21 TC 0 Z9 0 U1 2 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1040-1334 EI 1532-8015 J9 TEACH LEARN MED JI Teach. Learn. Med. PD APR 2 PY 2016 VL 28 IS 2 BP 202 EP 209 DI 10.1080/10401334.2016.1146600 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DJ1BH UT WOS:000373937600010 PM 27064722 ER PT J AU Kraemer, KM Luberto, CM O'Bryan, EM Mysinger, E Cotton, S AF Kraemer, Kristen M. Luberto, Christina M. O'Bryan, Emily M. Mysinger, Erica Cotton, Sian TI Mind-Body Skills Training to Improve Distress Tolerance in Medical Students: A Pilot Study SO TEACHING AND LEARNING IN MEDICINE LA English DT Article DE medical students; mind-body; stress tolerance ID RANDOMIZED CONTROLLED-TRIAL; STRESS REDUCTION; TRANSDIAGNOSTIC TREATMENT; EMOTIONAL DISORDERS; SUICIDAL IDEATION; PERCEIVED STRESS; UNIFIED PROTOCOL; MINDFULNESS; INTERVENTION; VALIDATION AB Problem: Medical students face rigorous and stressful work environments, resulting in high rates of psychological distress. However, there has been a dearth of empirical work aimed at modifying risk factors for psychopathology among this at-risk group. Distress tolerance, defined as the ability to withstand emotional distress, is one factor that may be important in promoting psychological well-being in medical students. Thus, the aim of the current mixed-methods study was (a) to describe changes in facets of distress tolerance (i.e., emotional tolerance, absorption, appraisal, regulation) for medical students who completed a mind-body skills training group, and a no-intervention control group of students; (b) to examine the relationship between changes in psychological variables and changes in distress tolerance; and (c) to report students' perceptions of the mind-body group, with an emphasis on how the group may have affected personal and professional functioning due to improvements in distress tolerance. Intervention: The mind-body program was an 11-week, 2-hour skills training group that focused on introducing, practicing, and processing mind-body skills such as biofeedback, guided imagery, relaxation, several forms of meditation (e.g., mindfulness), breathing exercises, and autogenic training. Context: Participants were 52 first- and second-year medical students (62.7% female, M-age = 23.45, SD = 1.51) who participated in a mind-body group or a no-intervention control group and completed self-report measures before and after the 11-week period. Outcome: Students in the mind-body group showed a modest improvement in all distress tolerance subscales over time (Delta M = .42-.53, p = .01-.03, d = .44-.53), whereas the control group showed less consistent changes across most subscales (Delta M = .11-.42, p = .10-.65, d = .01-.42). Students in the mind-body group qualitatively reported an improved ability to tolerate affective distress. Overall, improvements in psychological symptoms were associated with improvements in distress tolerance in the mind-body group but not in the control group. Lessons Learned: These preliminary findings provide support for the notion that improving distress tolerance through mind-body skills training might serve to protect medical students from becoming functionally impaired by psychological distress. Thus, implementing mind-body skills training into medical school education may help to improve the psychological well-being of medical students. Future studies utilizing more methodologically rigorous designs are warranted. C1 [Kraemer, Kristen M.; O'Bryan, Emily M.] Univ Cincinnati, Dept Psychol, Cincinnati, OH 45221 USA. [Luberto, Christina M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Mysinger, Erica; Cotton, Sian] Univ Cincinnati, Dept Family & Community Med, ML 0566, Cincinnati, OH 45206 USA. RP Cotton, S (reprint author), Univ Cincinnati, Dept Family & Community Med, ML 0566, Cincinnati, OH 45206 USA. EM sian.cotton@uc.edu FU UC Center for Integrative Health and Wellness FX Funding for this project was provided by UC Center for Integrative Health and Wellness. NR 46 TC 1 Z9 1 U1 8 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1040-1334 EI 1532-8015 J9 TEACH LEARN MED JI Teach. Learn. Med. PD APR 2 PY 2016 VL 28 IS 2 BP 219 EP 228 DI 10.1080/10401334.2016.1146605 PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DJ1BH UT WOS:000373937600012 PM 27064724 ER PT J AU Brun, C Daali, Y Combescure, C Zufferey, A Michelson, AD Fontana, P Reny, JL Frelinger, AL AF Brun, Charlotte Daali, Youssef Combescure, Christophe Zufferey, Anne Michelson, Alan D. Fontana, Pierre Reny, Jean-Luc Frelinger, Andrew L., III TI Aspirin response: Differences in serum thromboxane B2 levels between clinical studies SO PLATELETS LA English DT Article DE Aspirin; thromboxane B2; blood platelets; cardiovascular diseases; cohort studies ID STABLE CARDIOVASCULAR PATIENTS; LOW-DOSE ASPIRIN; PLATELET-AGGREGATION; RESISTANCE; METAANALYSIS; EVENTS; RISK; RESPONSIVENESS; CLOPIDOGREL; INHIBITION AB Serum thromboxane B2 (TxB2) is a specific marker of platelet inhibition by aspirin. Yet, TxB2 levels differ by up to 10-fold between some aspirin-treated patient cohorts. This study aimed to identify factors responsible for differences in serum TxB2 between cohorts in the ADRIE study (n = 657) and the BOSTON study (n = 678) of aspirin-treated cardiovascular patients originally tested with different ELISA assays. TxB2 levels were assessed in representative subgroups of the two cohorts (34 samples in BOSTON and 39 in ADRIE) by both ELISAs, as well as liquid chromatography and tandem mass spectroscopy (MS). A multivariate analysis was performed on the whole cohort database to identify determinants of the difference of TxB2 levels between cohorts. There was no systematic bias between the original ELISA TxB2 values and the MS values and the median difference was small, 0.12 ng/ml, thus not explaining the difference between median TxB2 levels in the two study populations (7 and 0.6 ng/ml in the ADRIE and BOSTON studies, respectively). In the combined dataset of the ADRIE and BOSTON cohorts (n = 1342), body mass index, age, gender, aspirin dose, time from aspirin intake to blood draw, NSAID intake, platelet count and C-reactive protein were significantly associated with TxB2 levels. After adjustment for patient characteristics, the difference between cohorts did not decrease. Unexplained differences in serum TxB2 levels in different populations of aspirin-treated cardiovascular patients suggest that further studies are needed to confirm the role of serum TxB2 level as a prognostic factor or rather as a marker of therapeutic observance. C1 [Brun, Charlotte] Univ Hosp Geneva, Div Gen Internal Med, CH-1205 Geneva, Switzerland. [Brun, Charlotte; Daali, Youssef; Zufferey, Anne; Fontana, Pierre; Reny, Jean-Luc] Univ Geneva, Sch Med, Geneva Platelet Grp, CH-1211 Geneva, Switzerland. [Daali, Youssef] Univ Hosp Geneva, Div Clin Pharmacol, CH-1205 Geneva, Switzerland. [Combescure, Christophe] Univ Hosp Geneva, Div Clin Epidemiol, CH-1205 Geneva, Switzerland. [Michelson, Alan D.; Frelinger, Andrew L., III] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Platelet Res Studies,Div Hematol Oncol,Boston, 44 Binney St, Boston, MA 02115 USA. [Fontana, Pierre] Univ Hosp Geneva, Div Angiol & Haemostasis, CH-1205 Geneva, Switzerland. [Reny, Jean-Luc] Univ Hosp Geneva, Div Internal Med & Rehabil, Dept Internal Med Rehabil & Geriatr, Rue Gabrielle Perret Gentil 4, CH-1205 Geneva, Switzerland. RP Reny, JL (reprint author), Univ Hosp Geneva, Div Internal Med & Rehabil, Dept Internal Med Rehabil & Geriatr, Rue Gabrielle Perret Gentil 4, CH-1205 Geneva, Switzerland. EM jean-luc.reny@hcuge.ch FU Geneva University Hospitals; Swiss National Science Foundation [3200B0-116843]; Swiss Heart Foundation; Swiss Society of Angiology; Internal Medicine Department of Geneva hospitals [PRD-06-II-10]; French ministry of health [PHRC APR 2005-14R-11]; Bristol-Myers Squibb; Eisai; GLSynthesis; Lilly/Daiichi Sankyo; McNeil Consumer Healthcare; Pfizer; Sanofi Aventis FX The study was supported by a "jeune chercheur" grant, provided by the Geneva University Hospitals. The ADRIE study was supported by grants from the Swiss National Science Foundation (grant No. 3200B0-116843), the Swiss Heart Foundation, the Swiss Society of Angiology, the Internal Medicine Department of Geneva hospitals (PRD-06-II-10) and the French ministry of health (PHRC APR 2005-14R-11). The sponsor had neither role in study design, the collection, analysis and interpretation of data, the writing of the report, nor in the decision to submit the article for publication. Alan Michelson and Andrew Frelinger have been principal investigator or co-investigator on research grants from Bristol-Myers Squibb, Eisai, GLSynthesis, Lilly/Daiichi Sankyo, McNeil Consumer Healthcare, Pfizer and Sanofi Aventis. Alan Michelson has been a member of data monitoring committees of Lilly/Daiichi Sankyo clinical trials. Andrew Frelinger has been a consultant to PLx Pharma. Pierre Fontana received honoraria from CSL Behring, Siemens and Bayer. Charlotte Brun, Youssef Daali, Christophe Combescure, Anne Zufferey and Jean-Luc Reny have no conflict of interest to disclose. NR 30 TC 1 Z9 1 U1 3 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0953-7104 EI 1369-1635 J9 PLATELETS JI Platelets PD APR 2 PY 2016 VL 27 IS 3 BP 196 EP 202 DI 10.3109/09537104.2015.1072147 PG 7 WC Cell Biology; Hematology SC Cell Biology; Hematology GA DI9VB UT WOS:000373849700003 PM 26270593 ER PT J AU Ko, SJ Park, K Kim, J Kim, M Kim, JH Lee, J Mohamed, AZ Yeo, I Kim, J Choi, SM Kim, H Park, JW Lee, JH AF Ko, Seok-Jae Park, Kyungmo Kim, Jieun Kim, Minji Kim, Joo-Hee Lee, Jeungchan Mohamed, Abdalla Z. Yeo, Inkwon Kim, Jinsung Choi, Sun-Mi Kim, Honggeol Park, Jae-Woo Lee, Jun-Hwan TI Effect of acupuncture and its influence on cerebral activity in functional dyspepsia patients: study protocol for a randomized controlled trial SO TRIALS LA English DT Article DE Functional dyspepsia; Acupuncture; Streitberger needle; Functional magnetic resonance imaging; Metabolomics ID QUALITY-OF-LIFE; IRRITABLE-BOWEL-SYNDROME; HEART-RATE-VARIABILITY; NEPEAN DYSPEPSIA; SYMPTOM SEVERITY; BRAIN ACTIVITY; GASTROINTESTINAL DISORDERS; POSTOPERATIVE NAUSEA; PERSONALITY-TRAITS; PLACEBO NEEDLE AB Background: Functional dyspepsia (FD) is a prevalent gastric disorder that is difficult to manage due to lack of satisfactory treatments. Acupuncture has been studied with regard to the rising need for treating FD, but the mechanism verifying its efficacy has not yet been fully revealed. The aim of this study is to explore the efficacy and mechanism of acupuncture for FD compared with a sham group. Methods/design: We describe a proposal for a randomized, assessor-blind, sham-controlled trial with 70 eligible participants who will be randomly allocated either into an acupuncture or a sham group. Participants in the acupuncture group will receive 10 sessions of real acupuncture treatment and those in the sham group will be treated with identical sessions using a Streitberger needle. Functional magnetic resonance imaging (fMRI) and metabolomics studies will be implemented before and after 4 weeks of treatment to investigate the mechanism of acupuncture. The primary outcome is a proportion of responders with adequate symptom relief and the secondary outcomes include the Nepean Dyspepsia Index - Korean version, Functional Dyspepsia-Related Quality of Life questionnaire, Ways of Coping Questionnaire, Coping Strategies Questionnaire, perception of bodily sensation questionnaire, State-Trait Anxiety Inventory, and the Center for Epidemiological Studies - Depression Scale. The outcomes will be evaluated before and after the treatment. Discussion: This is the first large-scale trial evaluating the efficacy and mechanism of acupuncture with fMRI and metabolomic methods. We will compare real acupuncture with the Streitberger sham needle to verify the specific effect of acupuncture. The results of this trial are expected to be relevant evidences affecting policy and decision-makers associated with routine healthcare. C1 [Ko, Seok-Jae; Kim, Minji; Kim, Jinsung; Park, Jae-Woo] Kyung Hee Univ, Coll Korean Med, Dept Gastroenterol, Seoul, South Korea. [Park, Kyungmo; Lee, Jeungchan; Mohamed, Abdalla Z.] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. [Kim, Jieun; Kim, Joo-Hee; Choi, Sun-Mi; Lee, Jun-Hwan] Korea Inst Oriental Med, Div Clin Res, Daejeon, South Korea. [Yeo, Inkwon] Sookmyung Womens Univ, Dept Stat, Seoul, South Korea. [Kim, Honggeol] Kyung Hee Univ, Grad Sch, Dept Clin Korean Med, Seoul, South Korea. [Lee, Jeungchan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA. [Lee, Jun-Hwan] Univ Sci & Technol, Korean Med Life Sci, Campus Korea Inst Oriental Med, Daejeon, South Korea. RP Park, JW (reprint author), Kyung Hee Univ, Coll Korean Med, Dept Gastroenterol, Seoul, South Korea.; Lee, JH (reprint author), Korea Inst Oriental Med, Div Clin Res, Daejeon, South Korea. EM pjw2907@khu.ac.kr; omdjun@kiom.re.kr FU Korea Institute of Oriental Medicine [C16200] FX This research was supported by the Korea Institute of Oriental Medicine (C16200). NR 65 TC 0 Z9 0 U1 3 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD APR 2 PY 2016 VL 17 AR 183 DI 10.1186/s13063-016-1296-2 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DI4SA UT WOS:000373488400005 PM 27039086 ER PT J AU Ben Ami, E Demetri, GD AF Ben Ami, Eytan Demetri, George D. TI A safety evaluation of imatinib mesylate in the treatment of gastrointestinal stromal tumor SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE sarcoma; Targeted therapy; kinase inhibitor; Oncogene; Tyrosine kinase ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; STEVENS-JOHNSON-SYNDROME; SOFT-TISSUE SARCOMAS; C-KIT; PHASE-II; BCR-ABL; PRACTICAL MANAGEMENT; CUTANEOUS REACTIONS; RECEIVING IMATINIB AB Introduction: For the last 15years, imatinib mesylate has been the first line treatment of choice for advanced (metastatic) GIST. Areas covered: This review describes key efficacy data on imatinib for the treatment of GIST, and focuses on safety and tolerability of imatinib, with emphasis on common adverse events management and long term toxicity profile. Expert opinion: Imatinib has been the standard of care for metastatic GIST and probably will continue to be so for the next few years. Still, despite dramatic responses initially, imatinib drug resistance continues to be the major factor for treatment discontinuation. The toxicity profile of imatinib has been well characterized, and although the majority of patients experience an adverse event during treatment with imatinib, these side effects are usually mild and manageable, with the majority of patients continuing treatment uninterruptedly. Early concerns regarding imatinib related cardiotoxicity in GIST have not been confirmed in large prospective randomized trials, with reports indicating a low incidence of approximately 0.2%-0.4%. Future strategies for treatment of imatinib resistant GIST will probably include novel tyrosine kinase inhibitors, combination therapies or immunotherapy. C1 [Ben Ami, Eytan] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Demetri, George D.] Dana Farber Canc Inst, Ludwig Ctr Harvard, Boston, MA USA. [Demetri, George D.] Harvard Univ, Sch Med, Boston, MA USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ludwig Ctr Harvard, Boston, MA USA.; Demetri, GD (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM george_demetri@dfci.harvard.edu FU Bayer; Pfizer; EMD Serono; Janssen Oncology; GlaxoSmithKline; Sanofi Oncology; Daiichi-Sankyo; Ariad; Astra-Zeneca; ZioPharm; Polaris Pharmaceuticals; WIRB Copernicus Group; Kolltan Pharmaceuticals; Blueprint Medicine; GI therapeutics; Caris; Chapions Oncology; Bessor Pharmaceuticals; Novartis FX GD Demetri has acted as consultant and received consulting fees from Bayer and has received research support to Dana-Farber for specific clinical trial agreements in the sarcoma unit. He has received consulting fees and acted as a consultant for Novartis and has a patent licensed to Novartis from Dana-Farber with a royalty paid to Dana-Farber. He has received consulting fees and acted as consultant and received research support to Dana-Farber for specific clinical trial agreements in the sarcoma unit from Pfizer, EMD Serono, Janssen Oncology, GlaxoSmithKline. and Sanofi Oncology. He has acted as consultant and received consulting fees from Daiichi-Sankyo, Ariad, Astra-Zeneca, ZioPharm, Polaris Pharmaceuticals and WIRB Copernicus Group. He has acted as consultant, and received scientific advisory board consulting fees and Equity (minor stake, non public) from Kolltan Pharmaceuticals. He is a member of the board of directors and received scientific advisory fees and equity (minor stake, non public) from Blueprint Medicine. He is a consultant for and received scientific advisory fees and equity (minor stake, non public) from GI therapeutics, Caris, Chapions Oncology and Bessor Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed NR 62 TC 1 Z9 1 U1 4 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1474-0338 EI 1744-764X J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD APR 2 PY 2016 VL 15 IS 4 BP 571 EP 578 DI 10.1517/14740338.2016.1152258 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DH5MU UT WOS:000372834400001 PM 26865352 ER PT J AU Canellos, G Devita, V AF Canellos, George Devita, Vincent TI Gianni Bonadonna (1934-2015) OBITUARY SO LEUKEMIA & LYMPHOMA LA English DT Biographical-Item C1 [Canellos, George] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Devita, Vincent] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. RP Canellos, G (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM george.canellos@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 2 PY 2016 VL 57 IS 4 BP 739 EP 739 DI 10.3109/10428194.2015.1122401 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA DG6LN UT WOS:000372196100001 PM 26752549 ER PT J AU Peng, J Hasserjian, RP Tang, GL Patel, KP Goswami, M Jabbour, EJ Garcia-Manero, G Medeiros, LJ Wang, SA AF Peng, Jie Hasserjian, Robert P. Tang, Guilin Patel, Keyur P. Goswami, Maitrayee Jabbour, Elias J. Garcia-Manero, Guillermo Medeiros, L. Jeffrey Wang, Sa A. TI Myelodysplastic syndromes following therapy with hypomethylating agents (HMAs): development of acute erythroleukemia may not influence assessment of treatment response SO LEUKEMIA & LYMPHOMA LA English DT Article DE therapy; myelodysplastic syndrome; hypomethylating agents; erythroid predominance; Acute erythroid leukemia ID ACUTE MYELOID-LEUKEMIA; ACUTE ERYTHROID LEUKEMIA; INTERNATIONAL WORKING GROUP; CONVENTIONAL CARE REGIMENS; PROGNOSTIC SCORING SYSTEM; WORLD-HEALTH-ORGANIZATION; 5-AZA-2'-DEOXYCYTIDINE DECITABINE; OPEN-LABEL; PHASE-III; CRITERIA AB This study followed 28 patients with myelodysplastic syndromes (MDS) who showed a rise of bone marrow (BM) erythroids to >= 50% following three cycles (1-60) of hypomethylating agent (HMA) therapy. If BM blasts were calculated as a percentage of non-erythroids, 12 (42.9%) patients met the diagnostic criteria for acute erythroleukemia, erythroid/myeloid (AEL). However, none of the patients showed clonal cytogenetic evolution or new mutations. When compared to 47 de novo AEL patients, these 12 patients were less anemic and thrombocytopenic, had less complex karyotypes (p = 0.044) and showed a longer survival, either calculated from diagnosis (p < 0.001) or from the time of AEL (p = 0.005). These findings illustrate that >= 50% erythroids may appear in BM post-HMA therapy, likely a combination of reduction of BM granulocytes (p < 0.001) and promotion of normal or abnormal erythroid proliferation. Enumeration of blasts as a percentage of non-erythroid cells may lead to a diagnosis of AEL and mis-interpretation as disease progression. C1 [Peng, Jie; Tang, Guilin; Patel, Keyur P.; Goswami, Maitrayee; Medeiros, L. Jeffrey; Wang, Sa A.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Jabbour, Elias J.; Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. RP Wang, SA (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 72,1515 Holcombe Blvd, Houston, TX 77030 USA. EM swang5@mdanderson.org FU NCI NIH HHS [P30 CA016672] NR 33 TC 5 Z9 5 U1 0 U2 2 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 APR 2 PY 2016 VL 57 IS 4 BP 812 EP 819 DI 10.3109/10428194.2015.1079318 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA DG6LN UT WOS:000372196100013 PM 26293512 ER PT J AU Chen, Q Ayer, T Nastoupil, LJ Koff, JL Staton, AD Chhatwal, J Flowers, CR AF Chen, Qiushi Ayer, Turgay Nastoupil, Loretta J. Koff, Jean L. Staton, Ashley D. Chhatwal, Jagpreet Flowers, Christopher R. TI Population-specific prognostic models are needed to stratify outcomes for African-Americans with diffuse large B-cell lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article DE Lymphoma; risk; prognostication; race; outcomes; survival ID NON-HODGKIN-LYMPHOMA; ARTIFICIAL NEURAL-NETWORKS; CHOP-LIKE CHEMOTHERAPY; CANCER RISK-ESTIMATION; BREAST-CANCER; RACIAL-DIFFERENCES; ELDERLY-PATIENTS; UNITED-STATES; LOGISTIC-REGRESSION; PREDICT SURVIVAL AB Diffuse large B-cell lymphoma (DLBCL) demonstrates significant racial differences in age of onset, stage, and survival. To examine whether population-specific models improve prediction of outcomes for African-American (AA) patients with DLBCL, we utilized Surveillance, Epidemiology, and End Results data and compared stratification by the international prognostic index (IPI) in general and AA populations. We also constructed and compared prognostic models for general and AA populations using multivariable logistic regression (LR) and artificial neural network approaches. While the IPI adequately stratified outcomes for the general population, it failed to separate AA DLBCL patients into distinct risk groups. Our AA LR model identified age >= 55 (odds ratio 0.45, [95% CI: 0.36, 0.56], male sex (0.75, [0.60, 0.93]), and stage III/IV disease (0.43, [0.34, 0.54]) as adverse predictors of 5-year survival for AA patients. In addition, general-population prognostic models were poorly calibrated for AAs with DLBCL, indicating a need for validated AA-specific prognostic models. C1 [Chen, Qiushi; Ayer, Turgay] Georgia Inst Technol, H Milton Stewart Sch Ind & Syst Engn, Atlanta, GA 30332 USA. [Nastoupil, Loretta J.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Div Canc Med, Houston, TX 77030 USA. [Koff, Jean L.; Staton, Ashley D.; Flowers, Christopher R.] Emory Univ, Winship Canc Inst, Dept Hematol Oncol, Atlanta, GA 30322 USA. [Chhatwal, Jagpreet] Univ Texas MD Anderson Canc Ctr, Dept Hlth Serv Res, Houston, TX 77030 USA. [Chhatwal, Jagpreet] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Chhatwal, Jagpreet] Harvard Univ, Sch Med, Boston, MA USA. RP Flowers, CR (reprint author), Emory Univ, 1365 Clifton Rd,NE Bldg B,Suite 4302, Atlanta, GA 30322 USA. EM crflowe@emory.edu RI Flowers, Christopher/F-1953-2010 OI Flowers, Christopher/0000-0002-9524-3990 FU NCI NIH HHS [R21 CA158686, T32 CA160040] NR 60 TC 0 Z9 0 U1 1 U2 1 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 APR 2 PY 2016 VL 57 IS 4 BP 842 EP 851 DI 10.3109/10428194.2015.1083098 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA DG6LN UT WOS:000372196100017 PM 26415108 ER PT J AU Gunnery, SD Ruben, MA AF Gunnery, Sarah D. Ruben, Mollie A. TI Perceptions of Duchenne and non-Duchenne smiles: A meta-analysis SO COGNITION & EMOTION LA English DT Article DE Duchenne smile; Non-Duchenne smile; Smile perceptions ID NON-ENJOYMENT SMILES; DETECTING HAPPINESS; NONENJOYMENT SMILES; FAKE SMILES; AUTHENTICITY; SENSITIVITY; EXPRESSIONS; CHILDRENS; GENUINE; MARKER AB A meta-analysis was conducted to compare perceptions of Duchenne smiles, smiles that include activation of the cheek raiser muscle that creates crow's feet around the eyes, with perceptions of non-Duchenne smiles, smiles without cheek raiser activation. In addition to testing the overall effect, moderator analyses were conducted to test how methodological, stimulus-specific and perceiver-specific differences between studies predicted the overall effect size. The meta-analysis found that, overall, Duchenne smiles and people producing Duchenne smiles are rated more positively (i.e., authentic, genuine, real, attractive, trustworthy) than non-Duchenne smiles and people producing non-Duchenne smiles. The difference between Duchenne and non-Duchenne smiles was greater when the stimuli were videos rather than photographs, when smiles were elicited naturally rather than through posing paradigms and when Duchenne and non-Duchenne smiles were not matched for intensity of the lip corner puller in addition to other perceiver and methodological moderators. C1 [Gunnery, Sarah D.] Tufts Univ, Dept Occupat Therapy, 26 Winthrop St, Medford, MA 02155 USA. [Ruben, Mollie A.] US Dept Vet Affairs, Ctr Healthcare Org & Implementat Res, Boston, MA USA. RP Gunnery, SD (reprint author), Tufts Univ, Dept Occupat Therapy, 26 Winthrop St, Medford, MA 02155 USA. EM sarah.gunnery@tufts.edu NR 36 TC 1 Z9 1 U1 6 U2 21 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0269-9931 EI 1464-0600 J9 COGNITION EMOTION JI Cogn. Emot. PD APR 2 PY 2016 VL 30 IS 3 BP 501 EP 515 DI 10.1080/02699931.2015.1018817 PG 15 WC Psychology, Experimental SC Psychology GA DB7VA UT WOS:000368723500008 PM 25787714 ER PT J AU Wormwood, JB Lynn, SK Barrett, LF Quigley, KS AF Wormwood, Jolie Baumann Lynn, Spencer K. Barrett, Lisa Feldman Quigley, Karen S. TI Threat perception after the Boston Marathon bombings: The effects of personal relevance and conceptual framing SO COGNITION & EMOTION LA English DT Article DE Threat perception; Threat accessibility; Framing; Terrorism; Signal detection theory ID SHOOT; BIAS; DECISIONS; TERRORISM; DISASTER; EMOTION; RISKS AB We examined how the Boston Marathon bombings affected threat perception in the Boston community. In a threat perception task, participants attempted to shoot armed targets and avoid shooting unarmed targets. Participants viewing images of the bombings accompanied by affectively negative music and text (e.g., Terror Strikes Boston) made more false alarms (i.e., more errors shooting unarmed targets) compared to participants viewing the same images accompanied by affectively positive music and text (e.g., Boston Strong) and participants who did not view bombing images. This difference appears to be driven by decreased sensitivity (i.e., decreased ability to distinguish guns from non-guns) as opposed to a more liberal bias (i.e., favouring the shoot response). Additionally, the more strongly affected the participant was by the bombings, the more their sensitivity was reduced in the negatively framed condition, suggesting that this framing was particularly detrimental to the most vulnerable individuals in the affected community. C1 [Wormwood, Jolie Baumann; Lynn, Spencer K.; Barrett, Lisa Feldman; Quigley, Karen S.] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Quigley, Karen S.] Edith Nourse Rogers Mem VA Hosp, Bedford, MA USA. RP Wormwood, JB (reprint author), Northeastern Univ, Dept Psychol NI 125, 360 Huntington Ave, Boston, MA 02115 USA. EM jbwormwood@gmail.com FU National Institutes of Health [R01MH093394, DP1O D003312]; US Army Research Institute for the Behavioral and Social Sciences [W5J9CQ-12-C-0028, W5J9CQ-12-C-0049] FX This research was supported by the National Institutes of Health [grant numbers R01MH093394, DP1O D003312] and the US Army Research Institute for the Behavioral and Social Sciences (contract numbers W5J9CQ-12-C-0028, W5J9CQ-12-C-0049). The views, opinions and/or findings contained in this paper are those of the authors and shall not be construed as an official Department of the Army position, policy or decision, unless so designated by other documents. NR 31 TC 2 Z9 2 U1 7 U2 38 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9931 EI 1464-0600 J9 COGNITION EMOTION JI Cogn. Emot. PD APR 2 PY 2016 VL 30 IS 3 BP 539 EP 549 DI 10.1080/02699931.2015.1010487 PG 11 WC Psychology, Experimental SC Psychology GA DB7VA UT WOS:000368723500010 PM 25707419 ER PT J AU March, MI Modest, AM Ralston, SJ Hacker, MR Gupta, M Brown, FM AF March, Melissa I. Modest, Anna M. Ralston, Steven J. Hacker, Michele R. Gupta, Munish Brown, Florence M. TI The effect of adopting the IADPSG screening guidelines on the risk profile and outcomes of the gestational diabetes population SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Diagnosis; gestational diabetes; outcomes; risk profile ID PREGNANCY OUTCOMES; CARBOHYDRATE INTOLERANCE; GLUCOSE-TOLERANCE; HYPERGLYCEMIA; WOMEN; MELLITUS; IMPACT AB Objective: To compare characteristics and outcomes of women diagnosed with gestational diabetes mellitus (GDM) by the newer one-step glucose tolerance test and those diagnosed with the traditional two-step method.Research design and methods: This was a retrospective cohort study of women with GDM who delivered in 2010-2011. Data are reported as proportion or median (interquartile range) and were compared using a Chi-square, Fisher's exact or Wilcoxon rank sum test based on data type.Results: Of 235 women with GDM, 55.7% were diagnosed using the two-step method and 44.3% with the one-step method. The groups had similar demographics and GDM risk factors. The two-step method group was diagnosed with GDM one week later [27.0 (24.0-29.0) weeks versus 26.0 (24.0-28.0 weeks); p=0.13]. The groups had similar median weight gain per week before diagnosis. After diagnosis, women in the one-step method group had significantly higher median weight gain per week [0.67 pounds/week (0.31-1.0) versus 0.56 pounds/week (0.15-0.89); p=0.047]. In the one-step method group more women had suspected macrosomia (11.7% versus 5.3%, p=0.07) and more neonates had a birth weight >4000g (13.6% versus 7.5%, p=0.13); however, these differences were not statistically significant. Other pregnancy and neonatal complications were similar.Conclusions: Women diagnosed with the one-step method gained more weight per week after GDM diagnosis and had a non-statistically significant increased risk for suspected macrosomia. Our data suggest the one-step method identifies women with at least equally high risk as the two-step method. C1 [March, Melissa I.; Modest, Anna M.; Ralston, Steven J.; Hacker, Michele R.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [March, Melissa I.; Ralston, Steven J.] Beth Israel Deaconess Med Ctr, Div Maternal Fetal Med, Boston, MA 02215 USA. [March, Melissa I.; Ralston, Steven J.; Hacker, Michele R.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Gupta, Munish] Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA USA. [Gupta, Munish] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Brown, Florence M.] Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA 02215 USA. [Brown, Florence M.] Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. [Brown, Florence M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Brown, FM (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Florence.brown@joslin.harvard.edu FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]; Harvard University FX This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. NR 21 TC 0 Z9 0 U1 2 U2 15 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD APR 2 PY 2016 VL 29 IS 7 BP 1141 EP 1145 DI 10.3109/14767058.2015.1038513 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DB7QL UT WOS:000368710600023 PM 25958989 ER PT J AU Zhou, ES Partridge, AH Blackmon, JE Morgan, E Recklitis, CJ AF Zhou, E. S. Partridge, A. H. Blackmon, J. E. Morgan, E. Recklitis, C. J. TI A pilot videoconference group stress management program in cancer survivors: lessons learned SO RURAL AND REMOTE HEALTH LA English DT Article DE cancer survivor; cognitive-behavioral intervention; oncology; survivorship; telehealth; USA; videoconference ID QUALITY-OF-LIFE; PSYCHOSOCIAL CARE; INTERVENTIONS; MEN AB Context: Cancer is a challenging experience and there is evidence that psychosocial interventions are effective at improving adjustment following treatment. At our cancer center, 14 cancer survivors (breast, prostate and blood cancers) completed a four-session cognitive-behavioral stress program. The first session was delivered at the survivor's local cancer center, where they were provided with a loaner tablet. The three subsequent sessions were delivered through group-based videoconference on the tablet. Session content was supplemented with a tailored ebook, designed specifically for this program. Participants provided feedback about the program as well as a standardized measure of perceived stress. Issues: Despite evidence that psychosocial programs are effective, there are significant barriers to dissemination, particularly for those residing in rural areas who do not live near academic medical centers where such programming is more readily available. Our experiences delivering a group-based videoconference program in cancer survivors are described, including positives and challenges associated with its design and implementation. Lessons learned: Study participants enrolled from across four different US states, and the majority reported at least a 30-minute commute to their cancer center. This travel burden played a meaningful role in their desire to participate in our videoconference-based program. Although participants reported that session content was well suited to addressing stress management concerns, and session facilitators were able to effectively teach program techniques (eg progressive muscle relaxation, cognitive-reframing) and that the program was helpful overall, only modest improvements in perceived stress were seen. Participants noted challenges of the delivery including feeling disconnected from others, difficulty focusing, technical problems, and a desire for a longer program. Thus, although the novel delivery of a group-based, psychosocial program using tablet videoconference is feasible in a survivorship program, and desired by cancer survivors, key improvements must be made in future efforts. Our enthusiasm about the potential of telehealth must be tempered with the reality that such delivery can present challenges that interfere with the intervention implementation and efficacy. Facilitators must proactively address both the technological and interpersonal challenges associated with the use of group-based videoconference in order to improve its ability to positively impact cancer survivors. Many of these issues can be resolved prior to program launch, and require foresight and planning on the part of the program team. C1 [Zhou, E. S.; Partridge, A. H.; Blackmon, J. E.; Morgan, E.; Recklitis, C. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zhou, ES (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU AUSTRALIAN RURAL HEALTH EDUC NETWORK PI DEAKIN WEST PA PO BOX 242, DEAKIN WEST, ACT 2600, AUSTRALIA SN 1445-6354 J9 RURAL REMOTE HEALTH JI Rural Remote Health PD APR-JUN PY 2016 VL 16 IS 2 AR 3863 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EJ9YL UT WOS:000393583300020 PM 27303955 ER PT J AU Walker, RH AF Walker, Ruth H. TI The non-Huntington disease choreas Five new things SO NEUROLOGY-CLINICAL PRACTICE LA English DT Review ID FAMILIAL DYSKINESIA; FACIAL MYOKYMIA; NEUROFERRITINOPATHY; MOVEMENT; SLEEP; ANTIBODIES; DISORDER; MUTATION AB Purpose of review: Chorea can be due to a wide variety of causes. In this review, I provide updates on several recently identified genetic and autoimmune causes of chorea, and review evidence supporting the use of deep brain stimulation in chorea. Recent findings: New genes that may cause chorea include ADCY5 (encoding for adenylate cyclase 5) C9ORF72 (in addition to amyotrophic lateral sclerosis and frontotemporal dementia), and those responsible for the neurodegeneration with brain iron accumulation disorders. Novel autoantibodies are increasingly being identified as associated with a variety of neurologic syndromes, including chorea, in both paraneoplastic and non-paraneoplastic settings. Deep brain stimulation can be a useful intervention in patients with chorea who do not respond to oral medications, whether due to neurodegenerative or nondegenerative causes. Summary: New causes of chorea continue to be identified. Correct diagnosis is essential for prognostication and treatment. C1 [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. EM ruth.walker@mssm.edu NR 20 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0402 EI 2163-0933 J9 NEUROL-CLIN PRACT JI Neurol.-Clin. Pract. PD APR PY 2016 VL 6 IS 2 BP 150 EP 156 DI 10.1212/CPJ.0000000000000236 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA EI6JT UT WOS:000392602400014 ER PT J AU Izquierdo-Garcia, D Catana, C AF Izquierdo-Garcia, David Catana, Ciprian TI MR Imaging-Guided Attenuation Correction of PET Data in PET/MR Imaging SO PET CLINICS LA English DT Review DE PET/MR imaging; Attenuation correction; MR-AC; Segmentation; Atlas; Template; Artifacts; Body truncation ID TIME-OF-FLIGHT; POSITRON-EMISSION-TOMOGRAPHY; ULTRASHORT-ECHO-TIME; WHOLE-BODY PET/MRI; SIMULTANEOUS ITERATIVE RECONSTRUCTION; SURFACE COILS; COMPUTED-TOMOGRAPHY; CLINICAL-ASSESSMENT; BONE ATTENUATION; METAL ARTIFACTS AB Attenuation correction (AC) is one of the most important challenges in the recently introduced combined PET/magnetic resonance (MR) scanners. PET/MR AC (MR-AC) approaches aim to develop methods that allow accurate estimation of the linear attenuation coefficients of the tissues and other components located in the PET field of view. MR-AC methods can be divided into 3 categories: segmentation, atlas, and PET based. This review provides a comprehensive list of the state-of-the-art MR-AC approaches and their pros and cons. The main sources of artifacts are presented. Finally, this review discusses the current status of MR-AC approaches for clinical applications. C1 [Izquierdo-Garcia, David; Catana, Ciprian] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. RP Izquierdo-Garcia, D (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM davidizq@nmr.mgh.harvard.edu NR 119 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1556-8598 EI 1559-7814 J9 PET CLIN JI PET Clin. PD APR PY 2016 VL 11 IS 2 BP 129 EP + DI 10.1016/j.cpet.2015.10.002 PG 23 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI3KF UT WOS:000392388700005 PM 26952727 ER PT J AU Koval, RD Mcdonagh, J Grubaugh, A Young, W Corcoran, B Lee, A Dumas, B Edlund, B AF Koval, Renee D. Mcdonagh, James Grubaugh, Anouk Young, Wendy Corcoran, Beth Lee, Angela Dumas, Bonnie Edlund, Barbara TI Implementation of Recovery Programming on an Inpatient Acute Psychiatric Unit and Its Impact on Readmission SO JOURNAL OF ADDICTIONS NURSING LA English DT Article DE mental health; readmissions; recovery; veterans ID ILLNESS MANAGEMENT AB Background: Recovery-oriented models of care are evidence based and have been shown to improve patient satisfaction and outcomes as well as decrease the percentage of readmissions to inpatient psychiatric units. Methods: This quality improvement project was implemented on a 16-bed inpatient adult mental health unit in a Veterans Affairs Medical Center. Percentages of readmissions were compared throughout the course of implementation of the recovery model. Readmissions during the months of July-September were tabulated over 3 subsequent years and compared readmission percentages before recovery implementation, during the early stage of recovery implementation, and finally, during ongoing recovery implementation. Results: A decrease in readmission percentages was seen with implementation of recovery-oriented care when comparing the same 3-month period over 3 years. Conclusion: After implementation of recovery-oriented care measures, there was a decrease in percentage of readmissions to the unit. In addition, this decrease was sustained and was shown to improve over time as recovery-oriented programming was further developed on the unit. These data suggest that Veterans Affairs Medical Centers should consider adding tools and procedures to successfully implement recovery programming on inpatient units and efforts should include direct involvement of patients in their own recovery journey, revision of policies and procedures to reflect the importance of recovery, thorough training of frontline staff regarding recovery principles, and transfer of recovery information directly from inpatient units to outpatient providers. C1 [Koval, Renee D.] Med Univ South Carolina, Coll Nursing, Charleston, SC USA. [Mcdonagh, James; Grubaugh, Anouk; Young, Wendy] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Corcoran, Beth] Lehigh Valley Hlth Network, LVPG Consultat Liaison Psychiat, Allentown, PA USA. [Lee, Angela] Multnomah Cty Hlth Dept Correct Hlth, Portland, OR USA. [Dumas, Bonnie; Edlund, Barbara] Med Univ South Carolina, Coll Nursing, Charleston, SC USA. RP Koval, RD (reprint author), 650 Enterprise Blvd Apt 1304, Charleston, SC 29492 USA. EM rkdnp15@gmail.com FU (Office of Academic Affiliations), at a south eastern VAMC; American Psychiatric Nurses Association FX The authors acknowledge the assistance of Dr. Christopher Pelic, MD, in preparation of the manuscript. In addition, the authors would also like to acknowledge the Psychiatric Nurse Practitioner Residency Program Directed by Dr. Janet York, PhD, PMHCS-BC, FAAN (funded by the Office of Academic Affiliations), at a south eastern VAMC and the American Psychiatric Nurses Association's Recovery to Practice training without which this project would not have been possible. NR 15 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1088-4602 EI 1548-7148 J9 J ADDICT NURS JI J. Addict. Nurs. PD APR-JUN PY 2016 VL 27 IS 2 BP 101 EP 108 DI 10.1097/JAN.0000000000000121 PG 8 WC Substance Abuse; Nursing SC Substance Abuse; Nursing GA EF0TO UT WOS:000390039100007 PM 27272994 ER PT J AU Brito-Zeron, P Bosch, X Ramos-Casals, M Stone, JH AF Brito-Zeron, Pilar Bosch, Xavier Ramos-Casals, Manuel Stone, John H. TI IgG4-related disease: Advances in the diagnosis and treatment SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Article DE IgG4-related disease; Autoimmune pancreatitis; Cholangitis; Fibrosis; Plasmablasts; Rituximab ID IMMUNOGLOBULIN G4-RELATED DISEASE; IGG4-POSITIVE PLASMA-CELLS; CHRONIC SCLEROSING SIALADENITIS; TYPE-1 AUTOIMMUNE PANCREATITIS; INFLAMMATORY-BOWEL-DISEASE; SERUM IGG4 CONCENTRATIONS; PRIMARY SJOGRENS-SYNDROME; OF-THE-LITERATURE; TUBULOINTERSTITIAL NEPHRITIS; MIKULICZS-DISEASE AB IgG4-related disease is a rare immune-mediated systemic disease with the capability of involving essentially any organ. Although the presenting clinical features vary substantially according to the speciality to which patients present first, perhaps the most common clinical presentation is that of single or multiple organ enlargement, arousing suspicion of cancer. The disease is frequently diagnosed unexpectedly in pathological specimens or on imaging studies. The diagnostic approach is complex and includes not only IgG4-related tests (serum levels, circulating plasmablasts, and specific immunohistochemical studies), but also clinical, laboratory, and imaging tests as well as the typical histopathological features (lymphocytic infiltration, storiform fibrosis, eosinophilic infiltration, and obliterative phlebitis). IgG4-related tests should not be considered as diagnostic in the absence of an appropriate clinical scenario. Therapeutic approaches reported to date pertain primarily to glucocorticoids, but the use of these medications has not been studied in a controlled or prospective manner. The most current investigational treatment approaches have focused on targeting cells of the B-cell lineage, including B-cell-depleting agents (rituximab) and a non-depleting homodimer monoclonal antibody targeting CD19 and Fc-gamma RIIIb. (C) 2016 Published by Elsevier Ltd. C1 [Brito-Zeron, Pilar] Hosp CIMA Sanitas, Dept Med, Autoimmune Dis Unit, Barcelona, Spain. [Brito-Zeron, Pilar; Ramos-Casals, Manuel] IDIBAPS CELLEX, Sjogren Syndrome Res Grp AGAUR, Lab Autoimmune Dis Josep Font, Barcelona, Spain. [Brito-Zeron, Pilar; Ramos-Casals, Manuel] Hosp Clin Barcelona, ICMiD, Dept Autoimmune Dis, Barcelona, Spain. [Bosch, Xavier] Hosp Clin Barcelona, ICMiD, Dept Internal Med, Barcelona, Spain. [Ramos-Casals, Manuel] Univ Barcelona, Dept Med, Barcelona, Spain. [Stone, John H.] Harvard Med Sch, Boston, MA 02114 USA. [Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. RP Ramos-Casals, M (reprint author), Hosp Clin Barcelona, Serv Malalties Autoimmunes Sistem, C Villarroel 170, Barcelona 08036, Spain. EM mramos@clinic.ub.es FU Fondo de Investigaciones Sanitarias [INT15/00085]; 'Ajut per a la Recerca Josep Font' (Hospital Clinic Barcelona) [HB-12-JF-BZ-C] FX This study was supported by grants - Fondo de Investigaciones Sanitarias INT15/00085 (MRC) and 'Ajut per a la Recerca Josep Font' HB-12-JF-BZ-C (PBZ, Hospital Clinic Barcelona 2012). NR 133 TC 1 Z9 1 U1 4 U2 4 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 APR PY 2016 VL 30 IS 2 BP 261 EP 278 DI 10.1016/j.berh.2016.07.003 PG 18 WC Rheumatology SC Rheumatology GA EE2EB UT WOS:000389395400005 PM 27886799 ER PT J AU Williams, TK Clouse, WD AF Williams, Timothy K. Clouse, W. Darrin TI Current concepts in repair of extremity venous injury SO Journal of Vascular Surgery-Venous and Lymphatic Disorders LA English DT Review ID BALAD VASCULAR REGISTRY; POPLITEAL ARTERY; LIMB LOSS; NATIONAL TRAUMA; VEIN REPAIR; DATA-BANK; EXPERIENCE; MANAGEMENT; RISK; MORTALITY AB Objective: Extremity venous injury management remains controversial. The purpose of this communication is to offer perspective as well as experiential and technical insight into extremity venous injury repair. Methods: Available literature is reviewed and discussed. Historical context is provided. Indication, the decision process for repair, including technical conduct, is delineated. In particular, the authors' experiences in both civilian and wartime injury are used for perspective. Results: Extremity venous injury repair was championed within data from the Vietnam Vascular Registry. However, patterns of extremity venous injury differ between combat and civilian settings. Since Vietnam, civilian descriptive series opine the benefits and potential complications associated with both venous injury repair and ligation. These surround extremity edema, chronic venous insufficiency, thromboembolism, and limb loss. Whereas no clear superiority in either approach has been identified to date, there appears to be no increased risk of pulmonary embolism or chronic venous changes with repair. Newer data from the wars in Iraq and Afghanistan and meta-analysis have reinforced this and also have suggested limb salvage benefit for extremity venous repair in combined arterial and venous injuries in modern settings. The patient's physiologic state and associated injury drive five triage categories suggesting vein injury management. Vein repair thrombosis occurs in a significant proportion, yet many recanalize and possibly have a positive impact on limb venous return. Further, early decompression favors reduced blood loss, acute edema, and inflammation, supporting collateral development. Large soft tissue injury minimizing collateral capacity increases the importance of repair. Constructs of repair are varied with modest differences in patency. Venous shunting is feasible, but specific roles remain nebulous. Conclusions: An aggressive posture toward extremity venous injury repair seems justified today because of the likely role in reducing venous hypertensive sequelae as well as a potential role in limb salvage. Appropriate triage selection for extremity vein repair is essential. C1 [Williams, Timothy K.] David Grant USAF Med Ctr, Heart Lung & Vasc Ctr, Dept Surg, Travis AFB, CA USA. [Williams, Timothy K.] Univ Calif Davis, Dept Surg, Sacramento, CA 95817 USA. [Clouse, W. Darrin] Harvard Med Sch, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Dept Surg, Boston, MA USA. [Clouse, W. Darrin] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. RP Clouse, WD (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,WACC 440, Boston, MA 02114 USA. EM wclouse@mgh.harvard.edu NR 45 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-333X J9 J VASC SURG-VENOUS L JI J. Vasc. Surg.-Venous Lymphat. Dis. PD APR PY 2016 VL 4 IS 2 BP 238 EP 247 DI 10.1016/j.jvsv.2015.07.003 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA ED7CK UT WOS:000389013100015 PM 26993874 ER PT J AU Evans, JR Zhao, SG Chang, L Tomlins, SA Erho, N Sboner, A Schiewer, MJ Spratt, DE Kothari, V Klein, EA Den, RB Dicker, AP Karnes, J Yu, XC Nguyen, PL Rubin, MA de Bono, J Knudsen, KE Davicioni, E Feng, FY AF Evans, Joseph R. Zhao, Shuang G. Chang, Laura Tomlins, Scott A. Erho, Nicholas Sboner, Andrea Schiewer, Matthew J. Spratt, Daniel E. Kothari, Vishal Klein, Eric A. Den, Robert B. Dicker, Adam P. Karnes, Jeffrey Yu, Xiaochun Nguyen, Paul L. Rubin, Mark A. de Bono, Johann Knudsen, Karen E. Davicioni, Elai Feng, Felix Y. TI Patient-Level DNA Damage and Repair Pathway Profiles and Prognosis After Prostatectomy for High-Risk Prostate Cancer SO JAMA ONCOLOGY LA English DT Article ID RADIATION-THERAPY; CONSERVATIVE MANAGEMENT; TISSUE BIOMARKER; METASTASIS; OUTCOMES; PROGRESSION; CLASSIFIER; RECURRENCE; EXPRESSION; GENES AB IMPORTANCE A substantial number of patients diagnosed with high-risk prostate cancer are at risk formetastatic progression after primary treatment. Better biomarkers are needed to identify patients at the highest risk to guide therapy intensification. OBJECTIVE To create a DNA damage and repair (DDR) pathway profiling method for use as a prognostic signature biomarker in high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS A cohort of 1090 patients with high-risk prostate cancer who underwent prostatectomy and were treated at 3 different academic institutions were divided into a training cohort (n = 545) and 3 pooled validation cohorts (n = 232, 130, and 183) assembled for case-control or case-cohort studies. Profiling of 9 DDR pathways using 17 gene sets for GSEA (Gene Set Enrichment Analysis) of high-density microarray gene expression data from formalin-fixed paraffin-embedded prostatectomy samples with median 10.3 years follow-up was performed. Prognostic signature development from DDR pathway profiles was studied, and DDR pathway gene mutation in published cohorts was analyzed. MAIN OUTCOMES AND MEASURES Biochemical recurrence-free, metastasis-free, and overall survival. RESULTS Across the training cohort and pooled validation cohorts, 1090 men were studied; mean (SD) age at diagnosis was 65.3 (6.4) years. We found that there are distinct clusters of DDR pathways within the cohort, and DDR pathway enrichment is only weakly correlated with clinical variables such as age (Spearman rho [rho], range, -0.07 to 0.24), Gleason score (rho, range, 0.03 to 0.20), prostate-specific antigen level (rho, range, -0.07 to 0.10), while 13 of 17 DDR gene sets are strongly correlated with androgen receptor pathway enrichment (rho, range, 0.33 to 0.82). In published cohorts, DDR pathway genes are rarely mutated. A DDR pathway profile prognostic signature built in the training cohort was significantly associated with biochemical recurrence-free, metastasis-free, and overall survival in the pooled validation cohorts independent of standard clinicopathological variables. The prognostic performance of the signature for metastasis-free survival appears to be stronger in the younger patients (HR, 1.67; 95% CI, 1.12-2.50) than in the older patients (HR, 0.77; 95% CI, 0.29-2.07) on multivariate Cox analysis. CONCLUSIONS AND RELEVANCE DNA damage and repair pathway profiling revealed patient-level variations and the DDR pathways are rarely affected by mutation. A DDR pathway signature showed strong prognostic performance with the long-term outcomes of metastasis-free and overall survival that may be useful for risk stratification of high-risk prostate cancer patients. C1 [Evans, Joseph R.; Zhao, Shuang G.; Chang, Laura; Spratt, Daniel E.; Kothari, Vishal; Feng, Felix Y.] Univ Michigan, Dept Radiat Oncol, 1500 E Med Ctr Dr,UHB2C490 SPC5010, Ann Arbor, MI 48109 USA. [Zhao, Shuang G.] Beaumont Hosp, Transit Year Program, Dearborn, MI USA. [Tomlins, Scott A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Erho, Nicholas; Davicioni, Elai] GenomeDx Biosci Inc, Vancouver, BC, Canada. [Sboner, Andrea; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [Sboner, Andrea; Rubin, Mark A.] New York Presbyterian Hosp, New York, NY USA. [Schiewer, Matthew J.; Knudsen, Karen E.] Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA. [Den, Robert B.; Dicker, Adam P.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Philadelphia, PA 19107 USA. [Karnes, Jeffrey] Mayo Clin, Dept Urol, Rochester, MN USA. [Yu, Xiaochun] City Hope Natl Med Ctr, Duarte, CA USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [Nguyen, Paul L.] Harvard Med Sch, Dept Radiat Oncol, Boston, MA USA. [de Bono, Johann] Royal Marsden NHS Fdn Trust, Drug Dev Unit, London, England. [de Bono, Johann] Royal Marsden NHS Fdn Trust, Prostate Canc Targeted Therapy Grp, London, England. [de Bono, Johann] Inst Canc Res, London, England. [Feng, Felix Y.] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. [Feng, Felix Y.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Feng, FY (reprint author), Univ Michigan, Dept Radiat Oncol, 1500 E Med Ctr Dr,UHB2C490 SPC5010, Ann Arbor, MI 48109 USA. EM ffeng@med.umich.edu OI Spratt, Daniel/0000-0002-5973-4741 FU Prostate Cancer Foundation; Evans Foundation FX This research was supported by the Prostate Cancer Foundation (Challenge Grants awarded to Dr Feng, Dr Knudsen, Dr Rubin, Dr de Bono, Dr Evans, and Dr Tomlins) and the Evans Foundation. NR 26 TC 1 Z9 1 U1 1 U2 1 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 APR PY 2016 VL 2 IS 4 BP 471 EP 480 DI 10.1001/jamaoncol.2015.4955 PG 10 WC Oncology SC Oncology GA DW5KJ UT WOS:000383683200015 PM 26746117 ER PT J AU Norquist, BM Harrell, MI Brady, MF Walsh, T Lee, MK Gulsuner, S Bernards, SS Casadei, S Yi, Q Burger, RA Chan, JK Davidson, SA Mannel, RS DiSilvestro, PA Lankes, HA Ramirez, NC King, MC Swisher, EM Birrer, MJ AF Norquist, Barbara M. Harrell, Maria I. Brady, Mark F. Walsh, Tom Lee, Ming K. Gulsuner, Suleyman Bernards, Sarah S. Casadei, Silvia Yi, Qian Burger, Robert A. Chan, John K. Davidson, Susan A. Mannel, Robert S. DiSilvestro, Paul A. Lankes, Heather A. Ramirez, Nilsa C. King, Mary Claire Swisher, Elizabeth M. Birrer, Michael J. TI Inherited Mutations in Women With Ovarian Carcinoma SO JAMA ONCOLOGY LA English DT Article ID CANCER SUSCEPTIBILITY GENE; MISMATCH REPAIR GENES; GERMLINE MUTATIONS; BREAST-CANCER; CONFER SUSCEPTIBILITY; FANCONI-ANEMIA; FALLOPIAN-TUBE; SEQUENCE DATA; BRCA1; RAD51C AB IMPORTANCE Germline mutations in BRCA1 and BRCA2 are relatively common in women with ovarian, fallopian tube, and peritoneal carcinoma (OC) causing a greatly increased lifetime risk of these cancers, but the frequency and relevance of inherited mutations in other genes is less well characterized. OBJECTIVE To determine the frequency and importance of germline mutations in cancer-associated genes in OC. DESIGN, SETTING, AND PARTICIPANTS A study population of 1915 woman with OC and available germline DNA were identified from the University of Washington (UW) gynecologic tissue bank (n = 570) and from Gynecologic Oncology Group (GOG) phase III clinical trials 218 (n = 788) and 262 (n = 557). Patients were enrolled at diagnosis and were not selected for age or family history. Germline DNA was sequenced from women with OC using a targeted capture and multiplex sequencing assay. MAIN OUTCOMES AND MEASURES Mutation frequencies in OC were compared with the National Heart, Lung, and Blood Institute GO Exome Sequencing Project (ESP) and the Exome Aggregation Consortium (ExAC). Clinical characteristics and survival were assessed by mutation status. RESULTS Overall, the median (range) age at diagnosis was 60 (28-91) years in patients recruited from UW and 61 (23-87) years in patients recruited from the GOG trials. A higher number of black women were recruited from the GOG trials (4.3% vs 1.4%; P = .009); but in patients recruited from UW, there was a higher proportion of fallopian tube carcinomas (13.3% vs 5.7%; P < .001); stage I and II disease (14.6% vs 0%[GOG trials were restricted to advanced-stage cancer]); and nonserous carcinomas (29.9% vs 13.1%, P < .001). Of 1915 patients, 280 (15%) had mutations in BRCA1 (n = 182), or BRCA2 (n = 98), and 8 (0.4%) had mutations in DNA mismatch repair genes. Mutations in BRIP1 (n = 26), RAD51C (n = 11), RAD51D (n = 11), PALB2 (n = 12), and BARD1 (n = 4) were significantly more common in patients with OC than in the ESP or ExAC, present in 3.3%. Race, histologic subtype, and disease site were not predictive of mutation frequency. Patients with a BRCA2 mutation from the GOG trials had longer progression-free survival (hazard ratio [HR], 0.60; 95% CI, 0.45-0.79; P < .001) and overall survival (HR, 0.39; 95% CI, 0.25-0.60; P < .001) compared with those without mutations. CONCLUSIONS AND RELEVANCE Of 1915 patients with OC, 347 (18%) carried pathogenic germline mutations in genes associated with OC risk. PALB2 and BARD1 are suspected OC genes and together with established OC genes (BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH2, MLH1, PMS2, and MSH6) bring the total number of genes suspected to cause hereditary OC to 11. C1 [Norquist, Barbara M.; Harrell, Maria I.; Bernards, Sarah S.; Swisher, Elizabeth M.] Univ Washington, Dept Obstet & Gynecol, Div Gynecol Oncol, Seattle, WA 98195 USA. [Brady, Mark F.; Lankes, Heather A.] Roswell Pk Canc Ctr Inst, NRG Oncol Stat & Data Ctr, Buffalo, NY USA. [Walsh, Tom; Lee, Ming K.; Gulsuner, Suleyman; Casadei, Silvia; King, Mary Claire; Swisher, Elizabeth M.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Walsh, Tom; Lee, Ming K.; Gulsuner, Suleyman; Casadei, Silvia; Yi, Qian; King, Mary Claire] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Burger, Robert A.] Univ Penn, Div Gynecol Oncol, Philadelphia, PA 19104 USA. [Chan, John K.] Calif Pacific Med Ctr, Sutter Hlth, Div Gynecol Oncol, San Francisco, CA USA. [Davidson, Susan A.] Univ Colorado, Div Gynecol Oncol, Denver, CO 80202 USA. [Mannel, Robert S.] Univ Oklahoma, Div Gynecol Oncol, Oklahoma City, OK USA. [DiSilvestro, Paul A.] Women & Infants Hosp Rhode Isl, Div Gynecol Oncol, Providence, RI USA. [Ramirez, Nilsa C.] Nationwide Childrens Hosp, Res Inst, Dept Pathol & Lab Med, Columbus, OH USA. [Birrer, Michael J.] Harvard Med Sch, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Norquist, BM (reprint author), Univ Washington, Dept Obstet & Gynecol, Div Gynecol Oncol, Seattle, WA 98195 USA. EM bnorquis@uw.edu FU National Cancer Institute [CA 27469]; Gynecologic Oncology Group Statistical and Data Center [CA 37517]; Gynecologic Oncology Group Tissue Bank [U10 CA27469, U24 CA114793, U10 CA180868]; NRG Oncology [1 U10 CA180822, R01CA131965, R01CA157744, R01CA175716, P50CA083636]; Ovarian Cancer Research Foundation; Breast Cancer Research Foundation; Department of Defense Ovarian Cancer Research Program [OC093285, OC120312]; Wendy Feuer Research Fund for Prevention and Treatment of Ovarian Cancer; Women's Reproductive Health Research Career Development Award [5K12HD001264-13]; Liz Tilberis Early Career Award from the Ovarian Cancer Research Foundation; Julie Fund; [RC4CA156551]; [R01CA142834] FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (grant No. CA 27469), the Gynecologic Oncology Group Statistical and Data Center (grant No. CA 37517), the Gynecologic Oncology Group Tissue Bank (grants U10 CA27469, U24 CA114793, and U10 CA180868); NRG Oncology (grants No. 1 U10 CA180822, R01CA131965 [Dr Swisher], RO1CA157744 [Dr King], R01CA175716 [DrWalsh, Dr King], and P50CA083636 [Dr Swisher]); and the Ovarian Cancer Research Foundation, The Breast Cancer Research Foundation, the Department of Defense Ovarian Cancer Research Program (grants No. OC093285 [DrWalsh] and OC120312 [Dr Swisher]), and the Wendy Feuer Research Fund for Prevention and Treatment of Ovarian Cancer. This study was also funded by the Women's Reproductive Health Research Career Development Award (5K12HD001264-13 [Dr Norquist]), the Liz Tilberis Early Career Award from the Ovarian Cancer Research Foundation (Dr Norquist). Dr Birrer also received grants RC4CA156551, R01CA142834, and financial support from the Julie Fund to support this study. NR 39 TC 33 Z9 33 U1 4 U2 5 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 APR PY 2016 VL 2 IS 4 BP 482 EP 490 DI 10.1001/jamaoncol.2015.5495 PG 9 WC Oncology SC Oncology GA DW5KJ UT WOS:000383683200017 PM 26720728 ER PT J AU Sun, MX Choueiri, TK Hamnvik, OPR Preston, MA De Velasco, G Jiang, W Loeb, S Nguyen, PL Trinh, QD AF Sun, Maxine Choueiri, Toni K. Hamnvik, Ole-Petter R. Preston, Mark A. De Velasco, Guillermo Jiang, Wei Loeb, Stacy Nguyen, Paul L. Quoc-Dien Trinh TI Comparison of Gonadotropin-Releasing Hormone Agonists and Orchiectomy Effects of Androgen-Deprivation Therapy SO JAMA ONCOLOGY LA English DT Article ID NONMETASTATIC PROSTATE-CANCER; RANDOMIZED-TRIALS; COMPETING RISK; MEDICARE DATA; MEN; TESTOSTERONE; INTERMITTENT; METAANALYSIS; FRACTURE; DISEASE AB IMPORTANCE Androgen-deprivation therapy (ADT) through surgical castration is equally effective as medical castration in controlling prostate cancer (PCa). However, the adverse effect profiles of both ADT groups have never been compared. OBJECTIVE To provide a comparative effectiveness analysis of the adverse effects of gonadotropin-releasing hormone agonists (GnRHa) vs bilateral orchiectomy in a homogeneous population. DESIGN, SETTING, AND PARTICIPANTS A population-based cohort of 3295 men with metastatic PCa between January 1995 and December 2009 66 years or older was selected from the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database. EXPOSURES Orchiectomy or GnRHa. MAIN OUTCOMES AND MEASURES Any fractures, peripheral arterial disease, venous thromboembolism, cardiac-related complications, diabetes mellitus, and cognitive disorders. To minimize treatment group biases, the inverse probability of treatment was weighted using the propensity score. Multivariable competing risk regression models were performed with the adjustment of all-cause mortality. Secondary analyses examined the effect of increasing duration of GnRHa treatment. Multivariable logistic regression models examined expenditures. RESULTS Overall, 3295 men with a primary diagnosis of metastatic PCa treated with GnRHa or orchiectomy were identified between years 1995 and 2009, and in adjusted analyses, patients who received a bilateral orchiectomy had significantly lower risks of experiencing any fractures (hazard ratio [HR], 0.77; 95% CI, 0.62-0.94; P = .01), peripheral arterial disease (HR, 0.65; 95% CI, 0.49-0.87; P = .004), and cardiac-related complications (HR, 0.74; 0.58-0.94; P = .01) compared with those treated with GnRHa. No statistically significant difference was noted between orchiectomy and GnRHa for diabetes and cognitive disorders. In individuals treated with GnRHa for 35 months or more, the increased risk for GnRHa compared with orchiectomy was noted for fractures (HR, 1.80), peripheral arterial disease (HR, 2.25), venous thromboembolism (HR, 1.52), cardiac-related complications (HR, 1.69), and diabetes mellitus (HR, 1.88) (P = .01 for all). At 12 months after PCa diagnosis, the median total expenditures was not significantly different between GnRHa and orchiectomy. CONCLUSIONS AND RELEVANCE Gonadotropin-releasing hormone agonist therapy is associated with higher risks of several clinically relevant adverse effects compared with orchiectomy. C1 [Sun, Maxine; Preston, Mark A.; Jiang, Wei; Quoc-Dien Trinh] Harvard Med Sch, Dana Farber Canc Inst, Brigham & Womens Hosp, Ctr Surg & Publ Hlth,Div Urol Surg, 45 Francis St,Urol ASB 2-3, Boston, MA 02115 USA. [Choueiri, Toni K.; De Velasco, Guillermo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hamnvik, Ole-Petter R.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, 75 Francis St, Boston, MA 02115 USA. [Hamnvik, Ole-Petter R.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Adult Survivorship Program, Boston, MA USA. [Loeb, Stacy] NYU, New York, NY USA. [Loeb, Stacy] Manhattan Vet Affairs Med Ctr, New York, NY USA. [Nguyen, Paul L.] Harvard Med Sch, Dana Farber Canc Inst, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. RP Trinh, QD (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Brigham & Womens Hosp, Ctr Surg & Publ Hlth,Div Urol Surg, 45 Francis St,Urol ASB 2-3, Boston, MA 02115 USA. EM qtrinh@bwh.harvard.edu OI Loeb, Stacy/0000-0003-3933-9207 FU Laura and Isaac Perlmutter New York University Cancer Center; Louis Feil Charitable Lead Trust; Vattikuti Urology Institute FX Dr Loeb is supported by the Laura and Isaac Perlmutter New York University Cancer Center and the Louis Feil Charitable Lead Trust. Dr Trinh is supported by an unrestricted educational grant from the Vattikuti Urology Institute and the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital. NR 31 TC 5 Z9 5 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD APR PY 2016 VL 2 IS 4 BP 500 EP 507 DI 10.1001/jamaoncol.2015.4917 PG 8 WC Oncology SC Oncology GA DW5KJ UT WOS:000383683200020 PM 26720632 ER PT J AU Howitt, BE Sun, HH Roemer, MGM Kelley, A Chapuy, B Aviki, E Pak, C Connelly, C Gjini, E Shi, YL Lee, L Viswanathan, A Horowitz, N Neuberg, D Crum, CP Lindeman, NL Kuo, F Ligon, AH Freeman, GJ Hodi, FS Shipp, MA Rodig, SJ AF Howitt, Brooke E. Sun, Heather H. Roemer, Margaretha G. M. Kelley, Alyssa Chapuy, Bjoern Aviki, Emeline Pak, Christine Connelly, Courtney Gjini, Evisa Shi, Yunling Lee, Larissa Viswanathan, Akila Horowitz, Neil Neuberg, Donna Crum, Christopher P. Lindeman, Neal L. Kuo, Frank Ligon, Azra H. Freeman, Gordon J. Hodi, F. Stephen Shipp, Margaret A. Rodig, Scott J. TI Genetic Basis for PD-L1 Expression in Squamous Cell Carcinomas of the Cervix and Vulva SO JAMA ONCOLOGY LA English DT Article ID MALIGNANCIES; INFECTION; DIAGNOSIS; LYMPHOMAS; CANCER AB IMPORTANCE Patients with squamous cell carcinoma (SCC) of the cervix or vulva have limited therapeutic options, and the potential for immunotherapy for this population has not been evaluated. Recent trials suggest that tumors with a genetic basis for PD-1 (programmed cell death protein 1) ligand expression are highly sensitive to therapeutic antibodies targeting PD-1. OBJECTIVE To determine the genetic status of CD274 (encoding PD-L1 [programmed cell death 1 ligand 1]) and PDCD1LG2 (encoding PD-L2 [programmed cell death 1 ligand 2]) in SCCs of the cervix and vulva and to correlate the findings with PD-L1 protein expression. DESIGN, SETTING, AND PARTICIPANTS We performed fluorescence in situ hybridization (FISH) using probes targeting CD274, PDCD1LG2, and the centromeric portion of chromosome 9, and immunohistochemistry (IHC) using an antibody recognizing PD-L1 on formalin-fixed, paraffin-embedded (FFPE) biopsy specimens from 48 cervical SCCs and 23 vulvar SCCs. MAIN OUTCOMES AND MEASURES Tumors were categorized according to the genetic abnormality in CD274 and PDCD1LG2 (coamplification > cogain > polysomy > disomy) as detected by FISH, and evaluated on a semiquantitative scale (modified H score, the product of the percentage of tumor cells with positive staining and the maximum intensity of positive staining) for PD-L1 protein expression as detected by IHC. RESULTS Overall, 71 samples of FFPE tissue from cases of cervical SCCs (n = 48) and vulvar SCCs (n = 23) were retrieved from the archives of Brigham and Women's Hospital and included in this study. We observed cogain or coamplification of CD274 and PDCD1LG2 in 32 of 48 cervical SCCs (67%) and 10 of 23 vulvar SCCs (43%). Median PD-L1 protein expression was highest among tumors with CD274 and PDCD1LG2 coamplification and lowest among tumors with disomy. CONCLUSIONS AND RELEVANCE Recurrent copy number gain of the genes encoding the PD-1 ligands provides a genetic basis for PD-L1 expression in a subset of cervical and vulvar SCCs and identifies a class of patients that are rational candidates for therapies targeting PD-1. C1 [Howitt, Brooke E.; Sun, Heather H.; Kelley, Alyssa; Pak, Christine; Connelly, Courtney; Gjini, Evisa; Shi, Yunling; Crum, Christopher P.; Lindeman, Neal L.; Kuo, Frank; Ligon, Azra H.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Roemer, Margaretha G. M.; Chapuy, Bjoern; Gjini, Evisa; Freeman, Gordon J.; Hodi, F. Stephen; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Aviki, Emeline; Lee, Larissa; Viswanathan, Akila; Horowitz, Neil] Brigham & Womens Hosp, Dept Obstet & Gynecol, Dept Obstet & Gynecol, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Gjini, Evisa; Freeman, Gordon J.; Hodi, F. Stephen; Shipp, Margaret A.; Rodig, Scott J.] Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Rodig, SJ (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM srodig@partners.org FU Center for Immuno-Oncology (CIO) at the Dana-Farber Cancer Institute; International Immuno-Oncology Network (IION) - Bristol-Myers-Squibb; National Institutes of Health [R01 NIH/NCI CA161026] FX Funding and support was provided by the Center for Immuno-Oncology (CIO) at the Dana-Farber Cancer Institute, a grant from the International Immuno-Oncology Network (IION) sponsored by Bristol-Myers-Squibb, and the National Institutes of Health (grant No. R01 NIH/NCI CA161026 [M.A.S.]). NR 15 TC 4 Z9 4 U1 1 U2 1 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 APR PY 2016 VL 2 IS 4 BP 518 EP 522 DI 10.1001/jamaoncol.2015.6326 PG 5 WC Oncology SC Oncology GA DW5KJ UT WOS:000383683200023 PM 26913631 ER PT J AU Sequist, LV Piotrowska, Z Niederst, MJ Heist, RS Digumarthy, S Shaw, AT Engelman, JA AF Sequist, Lecia V. Piotrowska, Zofia Niederst, Matthew J. Heist, Rebecca S. Digumarthy, Subba Shaw, Alice T. Engelman, Jeffrey A. TI Osimertinib Responses After Disease Progression in Patients Who Had Been Receiving Rociletinib SO JAMA ONCOLOGY LA English DT Letter ID CELL LUNG-CANCER; EGFR INHIBITOR; RESISTANCE; CRIZOTINIB; CERITINIB; AZD9291 C1 [Sequist, Lecia V.; Piotrowska, Zofia; Niederst, Matthew J.; Heist, Rebecca S.; Shaw, Alice T.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,POB 212, Boston, MA 02114 USA. [Sequist, Lecia V.; Piotrowska, Zofia; Niederst, Matthew J.; Heist, Rebecca S.; Digumarthy, Subba; Shaw, Alice T.; Engelman, Jeffrey A.] Harvard Med Sch, Boston, MA USA. [Digumarthy, Subba] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,POB 212, Boston, MA 02114 USA. EM lvsequist@partners.org FU NCI NIH HHS [2R01CA137008] NR 6 TC 9 Z9 9 U1 1 U2 3 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 APR PY 2016 VL 2 IS 4 BP 541 EP 543 DI 10.1001/jamaoncol.2015.5009 PG 3 WC Oncology SC Oncology GA DW5KJ UT WOS:000383683200027 PM 26720284 ER PT J AU Abdollah, F Sun, M Sammon, JD Choueiri, TK Menon, M Weissman, JS Trinh, QD AF Abdollah, Firas Sun, Maxine Sammon, Jesse D. Choueiri, Toni K. Menon, Mani Weissman, Joel S. Quoc-Dien Trinh TI Prevalence of Nonrecommended Screening for Prostate Cancer and Breast Cancer in the United States: A Nationwide Survey Analysis SO JAMA ONCOLOGY LA English DT Letter C1 [Abdollah, Firas; Sammon, Jesse D.; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Ctr Outcomes Res Analyt & Evaluat, 2799 W Grand Blvd, Detroit, MI 48202 USA. [Sun, Maxine; Quoc-Dien Trinh] Brigham & Womens Hosp, Div Urol Surg, 75 Francis St, Boston, MA 02115 USA. [Sun, Maxine; Weissman, Joel S.; Quoc-Dien Trinh] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Sun, Maxine; Weissman, Joel S.; Quoc-Dien Trinh] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Abdollah, F (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, Ctr Outcomes Res Analyt & Evaluat, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM firas.abdollah@gmail.com NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD APR PY 2016 VL 2 IS 4 BP 543 EP 545 DI 10.1001/jamaoncol.2015.5871 PG 4 WC Oncology SC Oncology GA DW5KJ UT WOS:000383683200028 PM 26794060 ER PT J AU Emani, S Healey, M Ting, DY Lipsitz, SR Ramelson, H Suric, V Bates, DW AF Emani, Srinivas Healey, Michael Ting, David Y. Lipsitz, Stuart R. Ramelson, Harley Suric, Vladimir Bates, David W. TI Awareness and Use of the After-Visit Summary Through a Patient Portal: Evaluation of Patient Characteristics and an Application of the Theory of Planned Behavior SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE patient portal; after-visit summary (AVS); meaningful use; electronic health records (EHRs); beliefs ID PERSONAL HEALTH RECORDS; MEANINGFUL-USE; INVITING PATIENTS; CLINICAL NOTES; DOCTORS NOTES; INFORMATION; ACCESS; SATISFACTION; PERCEPTIONS; EXPERIENCES AB Background: Patient portals are being used to provide a clinical summary of the office visit or the after-visit summary (AVS) to patients. There has been relatively little research on the characteristics of patients who access the AVS through a patient portal and their beliefs about the AVS. Objective: The aim was to (1) assess the characteristics of patients who are aware of and access the AVS through a patient portal and (2) apply the Theory of Planned Behavior (TPB) to predict behavioral intention of patients toward accessing the AVS provided through a patient portal. Methods: We developed a survey capturing the components of TPB (beliefs, attitude, perceived norm, and perceived behavioral control). Over a 6-month period, patients with a patient portal account with an office visit in the previous week were identified using our organization's scheduling system. These patients were sent an email about the study and a link to the survey via their portal account. We applied univariate statistical analysis (Pearson chi-square and 1-way ANOVA) to assess differences among groups (aware/unaware of AVS and accessed/did not access AVS). We reported means and standard deviations to depict belief strengths and presented correlations between beliefs and attitude, perceived norm, and perceived behavioral control. We used hierarchical regression analysis to predict behavioral intention toward accessing the AVS through the patient portal. Results: Of the 23,336 patients who were sent the survey, 5370 responded for a response rate of 23.01%. Overall, 76.52% (4109/5370) were aware that the AVS was available through the patient portal and 54.71% of those (2248/4109) accessed the AVS within 5 days of the office visit. Patients who accessed the AVS had a greater number of sessions with the portal (mean 119, SD 221.5) than those who did not access the AVS (mean 79.1, SD 123.3, P<.001); the difference was not significant for awareness of the AVS. The strongest behavioral beliefs with accessing the AVS were being able to track visits and tests (mean 2.53, SD 1.00) followed by having medical information more readily accessible (mean 2.48, SD 1.07). In all, 56.7% of the variance in intention to access the AVS through the portal was accounted for by attitude, perceived norm, and perceived behavioral control. Conclusions: Most users of a patient portal were aware that the AVS was accessible through the portal. Patients had stronger beliefs about accessing the AVS with the goal of timely and efficient access of information than with engaging in their health care. Interventions to improve patient access of the AVS can focus on providers promoting patient beliefs about the value of the AVS for tracking tests and visits, and timely and efficient access of information. C1 [Emani, Srinivas; Healey, Michael; Lipsitz, Stuart R.; Ramelson, Harley; Suric, Vladimir; Bates, David W.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. [Healey, Michael] Brigham & Womens Hosp, Brigham & Womens Phys Org, 75 Francis St, Boston, MA 02115 USA. [Ting, David Y.] Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. [Ramelson, Harley] Partners HealthCare, Informat Serv, Boston, MA USA. [Bates, David W.] Harvard Sch Publ Hlth, Dept Healthcare Policy & Management, Boston, MA USA. RP Emani, S (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM semani1@partners.org FU Partners Siemens Research Council (PSRC) FX The authors thank the Partners Siemens Research Council (PSRC) for funding the study, and Mohan Ganasekaran, Partners IS, for help with the programming required for the study. NR 26 TC 0 Z9 0 U1 3 U2 3 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD APR PY 2016 VL 18 IS 4 AR e77 DI 10.2196/jmir.5207 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA EC9VZ UT WOS:000388493700013 PM 27076485 ER PT J AU Chow, R Chiu, N Bruera, E Krishnan, M Chiu, L Lam, H DeAngelis, C Pulenzas, N Vuong, S Chow, E AF Chow, Ronald Chiu, Nicholas Bruera, Eduardo Krishnan, Monica Chiu, Leonard Lam, Henry DeAngelis, Carlo Pulenzas, Natalie Vuong, Sherlyn Chow, Edward TI Inter-rater reliability in performance status assessment among health care professionals: a systematic review SO ANNALS OF PALLIATIVE MEDICINE LA English DT Review DE Performance status (PS); Karnofsky performance status (KPS); Eastern Cooperative Oncology Group Performance Status (ECOG PS); palliative performance scale (PPS); inter-rater reliability ID ILL CANCER-PATIENTS; CELL LUNG-CANCER; PALLIATIVE-CARE; SURVIVAL PREDICTION; PROGNOSTIC-FACTORS; TERMINAL CANCER; OF-LIFE; INTEROBSERVER VARIABILITY; KARNOFSKY INDEX; ONCOLOGISTS AB Background: Studies have reported that performance status (PS) is a good prognostic indicator in patients with advanced cancer. However, different health care professionals (HCPs) could grade PS differently. The purpose of this review is to investigate the PS scores evaluated by different HCPs as reported in the literature. Methods: A literature search was conducted in Ovid MEDLINE and OLDMEDLINE from 1946 to Present (July 5, 2015), Embase Classic and Embase from 1947 to 2015 Week 26, and Cochrane Central Register of Controlled Trials up to May 2015. Information of interest was whether there was a difference of PS assessment between HCPs. Other statistical information provided to assess the agreement in ratings, such as Cohen's kappa coefficient, Krippendorff's alpha coefficient, Spearman Rank Coefficient, and Kendall's correlation, was noted. Results: Of the fifteen articles, eleven compared PS assessments between HCPs of different disciplines, one between the attending and resident physician, two between similarly-specialized physicians, and one between two unspecified-specialty physicians. Three studies reported a lack of agreement (kappa = 0.19-0.26; Krippendorff's alpha = 0.61-0.63), four reported moderate inter-rater reliability (kappa = 0.31-0.72), two reported mixed reliability, and six reported strong reliability (kappa = 0.91-0.92; Spearman rank correlation = 0.6-1.0; Kendall's correlation = 0.75-0.82). Four studies reported that Karnofsky performance status (KPS) had better inter-rater reliability than both the Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the palliative performance scale (PPS). Conclusions: The existing literature cites both good and bad inter-rater reliability of PS scores. It is difficult to conclude which HCPs' PS assessments are more accurate. C1 [Chow, Ronald; Chiu, Nicholas; Chiu, Leonard; Lam, Henry; DeAngelis, Carlo; Pulenzas, Natalie; Vuong, Sherlyn; Chow, Edward] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Bruera, Eduardo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Krishnan, Monica] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chow, E (reprint author), Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Dept Radiat Oncol, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM edward.chow@sunnybrook.ca NR 49 TC 1 Z9 1 U1 0 U2 0 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 2224-5820 EI 2224-5839 J9 ANN PALLIAT MED JI Ann. Pallliat. Med. PD APR PY 2016 VL 5 IS 2 BP 83 EP 92 DI 10.21037/apm.2016.03.02 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EB7RB UT WOS:000387586300003 PM 27121736 ER PT J AU Hall, TR Dizon, DS AF Hall, Tracilyn R. Dizon, Don S. TI Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian Cancer SO CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY LA English DT Article DE Advanced epithelial ovarian cancer; cytoreductive surgery; neoadjuvant chemotherapy ID PRIMARY DEBULKING SURGERY; PRIMARY CYTOREDUCTIVE SURGERY; PREOPERATIVE SERUM CA-125; LONG-TERM SURVIVAL; COMPUTED-TOMOGRAPHY; STAGE-III; SUBOPTIMAL CYTOREDUCTION; SURGICAL CYTOREDUCTION; RETROSPECTIVE ANALYSIS; PERITONEAL CARCINOMA AB The historical standard treatment paradigm for advanced epithelial ovarian cancer is surgical staging followed by adjuvant platinum-and taxane-based chemotherapy. It is well established that patients gain a survival advantage when optimal surgical debulking is achieved; surgical intervention that leaves bulky disease does not confer the same advantage. Thus, when optimal cytoreductive surgery is not possible or would lead to excessive morbidity, neoadjuvant chemotherapy followed by interval cytoreductive surgery is employed. There currently is no externally validated predictive model or consensus regarding which patients should be selected for primary debulking surgery vs neoadjuvant chemotherapy. This article reviews the current literature on the use of neoadjuvant chemotherapy as a treatment strategy for patients with advanced epithelial ovarian cancer. C1 [Hall, Tracilyn R.; Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hall, Tracilyn R.; Dizon, Don S.] Harvard Med Sch, Boston, MA USA. RP Dizon, DS (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM ddizon@partners.org NR 65 TC 0 Z9 1 U1 1 U2 1 PU MILLENNIUM MEDICAL PUBLISHING, INC PI NEW YORK PA 611 BROADWAY, STE 310, NEW YORK, NY 10012 USA SN 1543-0790 J9 CLIN ADV HEMATOL ONC JI Clin. Adv. Hematol. Oncol. PD APR PY 2016 VL 14 IS 4 BP 262 EP 268 PG 7 WC Oncology SC Oncology GA EB4HN UT WOS:000387331700009 PM 27166608 ER PT J AU Gold, D Henle, J Huang, C Lyve, T Marin, T Osorio, J Puligandla, M Weick, B Xia, J Yun, H Zhang, J AF Gold, Daphne Henle, James Huang, Cherry Lyve, Tia Marin, Tara Osorio, Jasmine Puligandla, Maneka Weick, Bayla Xia, Jing Yun, He Zhang, Jize TI Puzzling and apuzzling graphs SO AKCE INTERNATIONAL JOURNAL OF GRAPHS AND COMBINATORICS LA English DT Article DE Vertex coloring; Puzzles; Partitions AB Let G be a graph with chromatic number chi(G) and consider a partition P of G into connected subgraphs. P is a puzzle on G if there is a unique vertex coloring of G using 1, 2, ... , chi( G) such that the sums of the numbers assigned to the partition pieces are all the same. P is an apuzzle if there is a unique vertex coloring such that the sums are all different. We investigate the concept of puzzling and apuzzling graphs, detailing classes of graphs that are puzzling, apuzzling and neither. (C) 2016 Kalasalingam University. Publishing Services by Elsevier B.V. C1 [Henle, James; Huang, Cherry; Marin, Tara; Xia, Jing; Yun, He] Smith Coll, Northampton, MA 01063 USA. [Osorio, Jasmine] Lowes, Charlotte, NC 28269 USA. [Puligandla, Maneka] Dana Farber Inst, Boston, MA 02115 USA. [Weick, Bayla] Palantir Technol, New York, NY 10011 USA. [Zhang, Jize] Univ Washington, Seattle, WA 98195 USA. RP Henle, J (reprint author), Smith Coll, Northampton, MA 01063 USA. EM jhenle@smith.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU ARULMIGU KALASALINGAM COLL ENGINEERING PI TAMIL NADU PA ANANDNAGAR, KRISHNANKOIL, TAMIL NADU, 626 126, INDIA SN 0972-8600 J9 AKCE INT J GRAPHS CO JI AKCE Int. J. Graphs Comb. PD APR PY 2016 VL 13 IS 1 BP 1 EP 10 DI 10.1016/j.akcej.2016.02.001 PG 10 WC Mathematics SC Mathematics GA EA4FW UT WOS:000386567000001 ER PT J AU Aliberti, S Lonni, S Dore, S McDonnell, MJ Goeminne, PC Dimakou, K Fardon, TC Rutherford, R Pesci, A Restrepo, MI Sotgiu, G Chalmers, JD AF Aliberti, Stefano Lonni, Sara Dore, Simone McDonnell, Melissa J. Goeminne, Pieter C. Dimakou, Katerina Fardon, Thomas C. Rutherford, Robert Pesci, Alberto Restrepo, Marcos I. Sotgiu, Giovanni Chalmers, James D. TI Clinical phenotypes in adult patients with bronchiectasis SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; CYSTIC FIBROSIS BRONCHIECTASIS; CLUSTER-ANALYSIS; SYSTEMIC INFLAMMATION; COPD PHENOTYPES; VALIDATION; EMPHYSEMA; AIRWAY AB Bronchiectasis is a heterogeneous disease. This study aimed at identifying discrete groups of patients with different clinical and biological characteristics and long-term outcomes. This was a secondary analysis of five European databases of prospectively enrolled adult outpatients with bronchiectasis. Principal component and cluster analyses were performed using demographics, comorbidities, and clinical, radiological, functional and microbiological variables collected during the stable state. Exacerbations, hospitalisations and mortality during a 3-year follow-up were recorded. Clusters were externally validated in an independent cohort of patients with bronchiectasis, also investigating inflammatory markers in sputum. Among 1145 patients (median age 66 years; 40% male), four clusters were identified driven by the presence of chronic infection with Pseudomonas aeruginosa or other pathogens and daily sputum: "Pseudomonas" (16%), "Other chronic infection" (24%), "Daily sputum" (33%) and "Dry bronchiectasis" (27%). Patients in the four clusters showed significant differences in terms of quality of life, exacerbations, hospitalisations and mortality during follow-up. In the validation cohort, free neutrophil elastase activity, myeloperoxidase activity and interleukin-1 beta levels in sputum were significantly different among the clusters. Identification of four clinical phenotypes in bronchiectasis could favour focused treatments in future interventional studies designed to alter the natural history of the disease. C1 [Aliberti, Stefano; Lonni, Sara; Pesci, Alberto] Univ Milano Bicocca, Sch Med & Surg, AO San Gerardo, Via Pergolesi 33, I-20052 Monza, Italy. [Dore, Simone; Sotgiu, Giovanni] Univ Sassari Res, Dept Biomed Sci, Med Educ & Profess Dev Unit, Clin Epidemiol & Med Stat Unit,AOU Sassari, Sassari, Italy. [McDonnell, Melissa J.; Rutherford, Robert] Galway Univ Hosp, Dept Resp Med, Galway, Ireland. [Goeminne, Pieter C.] Univ Hosp Gasthuisberg, Dept Resp Med, Leuven, Belgium. [Goeminne, Pieter C.] UZ Leuven, Dept Resp Med, Leuven, Belgium. [Dimakou, Katerina] Sotiria Chest Hosp, Dept Pulm 5, Athens, Greece. [Fardon, Thomas C.; Chalmers, James D.] Univ Dundee, Tayside Resp Res Grp, Dundee, Scotland. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Div Pulm Dis & Crit Care, San Antonio, TX USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Aliberti, S (reprint author), Univ Milano Bicocca, Sch Med & Surg, AO San Gerardo, Via Pergolesi 33, I-20052 Monza, Italy. EM stefano.aliberti@unimib.it OI Aliberti, Stefano/0000-0002-0090-4531 FU European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC); European Respiratory Society; Bayer HealthCare; Aradigm Corporation; Medical Research Council; Wellcome Trust; European Respiratory Society/European Lung Foundation; Health Research Board, Ireland; National Heart, Lung and Blood Institute [K23HL096054] FX This study was supported by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC; www.bronchiectasis.eu). EMBARC is a European Respiratory Society Clinical Research Collaboration and has received funding from the European Respiratory Society, Bayer HealthCare and Aradigm Corporation. J.D. Chalmers acknowledges fellowship support from the Medical Research Council and the Wellcome Trust. M.J. McDonnell acknowledges fellowship support from the European Respiratory Society/European Lung Foundation and Health Research Board, Ireland. M.I. Restrepo's time is partially protected by Award Number K23HL096054 from the National Heart, Lung and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung and Blood Institute or the National Institutes of Health. The funding agencies had no role in the preparation, review or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 25 TC 23 Z9 22 U1 0 U2 1 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD APR PY 2016 VL 47 IS 4 BP 1113 EP 1122 DI 10.1183/13993003.01899-2015 PG 10 WC Respiratory System SC Respiratory System GA DZ6EW UT WOS:000385955400018 PM 26846833 ER PT J AU Kumar, ATN Rice, WL Lopez, JC Gupta, S Goergen, CJ Bogdanov, AA AF Kumar, Anand T. N. Rice, William L. Lopez, Jessica C. Gupta, Suresh Goergen, Craig J. Bogdanov, Alexei A., Jr. TI Substrate-Based Near-Infrared Imaging Sensors Enable Fluorescence Lifetime Contrast via Built-in Dynamic Fluorescence Quenching Elements SO ACS SENSORS LA English DT Article DE near-infrared; fluorescence lifetime; macromolecule; pegylated polylysine; enzyme; NIRDye 800CW ID PROTEASE ACTIVITY; PROBES; TUMORS; VIVO; TOMOGRAPHY; COPOLYMER; DELIVERY AB Enzymatic activity sensing in fluorescence lifetime (FLT) mode with "self-quenched" macromolecular near-infrared (NIR) sensors is a highly promising strategy for in vivo imaging of proteolysis. However, the mechanisms of FLT changes in such substrate-based NIR sensors have not yet been studied. We synthesized two types of sensors by linking the near-infrared fluorophore 1RDye 800CW to macromolecular graft copolymers of methoxy polyethylene glycol and polylysine (MPEG-gPLL) with varying degrees of MPEGylation and studied their fragmentation induced by trypsin, elastase, plasmin, and cathepsins (B,S,L,K). We determined that the efficiency of such NIR sensors in FLT mode depends on sensor composition. While MPEG-gPLL with a high degree of MPEGylation showed rapid (tau(1/2) = 0.1-0.2 min) FLT increase (Delta tau = 0.25 ns) upon model proteinase-mediated hydrolysis in vivo, lower MPEGylation density resulted in no such FLT increase. Temperature-dependence of fluorescence dequenching of NIR sensors pointed to a mixed dynamic/static-quenching mode of MPEG-gPLL-linked fluorophores. We further demonstrated that although the bulk of sensor-linked fluorophores elimination of static quenching, proteolysis-mediated deletion of a fraction of short (8-10 kD) negatively charged fragments of highly MPEGylated NIR sensor is the most likely event leading to a rapid FLT increase phenomenon in quenched NIR sensors. Therefore, the optimization of "built-in" dynamic quenching elements of macromolecular NIR sensors is a potential avenue for improving their response in FLT mode. C1 [Kumar, Anand T. N.; Rice, William L.] Massachusetts Gen Hosp, A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Kumar, Anand T. N.; Rice, William L.] Harvard Med Sch, Charlestown, MA 02129 USA. [Lopez, Jessica C.; Gupta, Suresh; Bogdanov, Alexei A., Jr.] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. [Lopez, Jessica C.; Gupta, Suresh; Bogdanov, Alexei A., Jr.] Univ Massachusetts, Sch Med, Lab Mol Imaging Probes, Worcester, MA 01655 USA. [Bogdanov, Alexei A., Jr.] Univ Massachusetts, Sch Med, Chem Biol Interface Program, Worcester, MA 01655 USA. [Goergen, Craig J.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. RP Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA.; Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, Lab Mol Imaging Probes, Worcester, MA 01655 USA.; Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, Chem Biol Interface Program, Worcester, MA 01655 USA. EM Alexei.Bogdanov@umassmed.edu FU NIH [R01EB000858-10, R01AG034901-04, R01 DK095728-01A1, R21 AI108529-01, R01EB015325] FX Funding has been provided by NIH grants: R01EB000858-10, R01AG034901-04, R01 DK095728-01A1, R21 AI108529-01 (to A.B.) and R01EB015325 (to A.T.N.K.). We are grateful to Julian Goding (UMMS) for optimizing and interpreting NMR spectra and Dr. Mary Mazzanti for editorial expertise. NR 40 TC 0 Z9 0 U1 5 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2379-3694 J9 ACS SENSORS JI ACS Sens. PD APR PY 2016 VL 1 IS 4 BP 427 EP 436 DI 10.1021/acssensors.5b00252 PG 10 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Chemistry; Science & Technology - Other Topics GA DY9OU UT WOS:000385464500017 ER PT J AU Jackevicius, CA Tu, JV Krumholz, HM Austin, PC Ross, JS Stukel, TA Koh, M Chong, A Ko, DT AF Jackevicius, Cynthia A. Tu, Jack V. Krumholz, Harlan M. Austin, Peter C. Ross, Joseph S. Stukel, Therese A. Koh, Maria Chong, Alice Ko, Dennis T. TI Comparative Effectiveness of Generic Atorvastatin and Lipitor (R) in Patients Hospitalized with an Acute Coronary Syndrome SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute coronary syndrome; comparative effectiveness; statin ID BRAND-NAME STATINS; CARDIOVASCULAR-DISEASE; PROPENSITY SCORE; KOREAN ADULTS; DRUGS; TOLERABILITY; PERCEPTIONS; MEDICATIONS; EQUIVALENCE; MULTICENTER AB Background-Although generic medications are approved based on bioequivalence with brand-name medications, there remains substantial concern regarding their clinical effectiveness and safety. Lipitor (R), available as generic atorvastatin, is one of the most commonly prescribed statins. Therefore, we compared the effectiveness of generic atorvastatin products and Lipitor (R). Methods and Results-We conducted a population-based cohort study, using propensity score matching to minimize potential confounding of patients >= 65 years, discharged alive after acute coronary syndrome (ACS) hospitalization between 2008 and 2012 in Ontario, Canada, who were prescribed Lipitor (R) or generic atorvastatin within 7 days of discharge. The primary outcome was 1-year death/recurrent ACS hospitalization. Secondary outcomes included hospitalization for heart failure, stroke, new-onset diabetes, rhabdomyolysis, and renal failure. In the 7863 propensity-matched pairs (15 726 patients), mean age was 76.9 years, 56.3% were male, 87.6% had myocardial infarction, and all patients had complete follow-up. At 1 year, 17.7% of those prescribed generic atorvastatin and 17.7% of those prescribed Lipitor (R) experienced death or recurrent ACS (hazard ratio, 1.00; 95% CI, 0.93-1.08; P= 0.94). No significant differences in rates of secondary outcomes between groups were observed. Prespecified subgroup analyses by age, sex, diabetes, atorvastatin dose, or admission diagnosis found no outcome difference between groups. Conclusions-Among older adults discharged alive after ACS hospitalization, we found no significant difference in cardiovascular outcomes or serious, infrequent side effects in patients prescribed generic atorvastatin compared with those prescribed Lipitor (R) at 1 year. Our findings support the use of generic atorvastatin in ACS, which could lead to substantial cost saving for patients and health care plans without diminishing population clinical effectiveness. C1 [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA USA. [Jackevicius, Cynthia A.; Tu, Jack V.; Austin, Peter C.; Stukel, Therese A.; Koh, Maria; Chong, Alice; Ko, Dennis T.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jackevicius, Cynthia A.; Tu, Jack V.; Austin, Peter C.; Stukel, Therese A.; Ko, Dennis T.] Univ Toronto, Fac Med, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Tu, Jack V.; Ko, Dennis T.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Div Cardiol, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Krumholz, Harlan M.] Yale Univ, Dept Med, Sect Cardiovasc Med, New Haven, CT 06520 USA. [Krumholz, Harlan M.; Ross, Joseph S.] Yale Univ, Yale New Haven Hosp, Sch Med, Ctr Outcomes Res & Evaluat, New Haven, CT USA. [Krumholz, Harlan M.] Yale Univ, Dept Epidemiol & Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06520 USA. [Krumholz, Harlan M.] Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. [Ross, Joseph S.] Yale Univ, Dept Med, Gen Internal Med Sect, New Haven, CT 06520 USA. RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E Second St, Pomona, CA 91766 USA. EM cjackevicius@westernu.edu FU Heart and Stroke Foundation (HSF) [G-14-0005977]; Ontario Ministry of Health and Long-Term Care (MOHLTC) FX This study was funded by a grant (G-14-0005977) from the Heart and Stroke Foundation (HSF). The Institute for Clinical Evaluative Sciences (ICES) is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. Furthermore, 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 were also independent from the funding sources. No endorsement by ICES, the MOHLTC, or the HSF is intended or should be inferred. NR 39 TC 1 Z9 1 U1 4 U2 4 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 APR PY 2016 VL 5 IS 4 AR e003350 DI 10.1161/JAHA.116.003350 PG 18 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DZ1PI UT WOS:000385609900033 PM 27098970 ER PT J AU Russo, BC Stamm, LM Raaben, M Kim, CM Kahoud, E Robinson, LR Bose, S Queiroz, AL Herrera, BB Baxt, LA Mor-Vaknin, N Fu, Y Molina, G Markovitz, DM Whelan, SP Goldberg, MB AF Russo, Brian C. Stamm, Luisa M. Raaben, Matthijs Kim, Caleb M. Kahoud, Emily Robinson, Lindsey R. Bose, Sayantan Queiroz, Ana L. Herrera, Bobby Brooke Baxt, Leigh A. Mor-Vaknin, Nirit Fu, Yang Molina, Gabriel Markovitz, David M. Whelan, Sean P. Goldberg, Marcia B. TI Intermediate filaments enable pathogen docking to trigger type 3 effector translocation SO NATURE MICROBIOLOGY LA English DT Article ID III SECRETION SYSTEM; NEEDLE TIP COMPLEX; SHIGELLA-FLEXNERI; PROTEIN SECRETION; EPITHELIAL-CELLS; PORE FORMATION; ENDOTHELIAL-CELLS; EUKARYOTIC CELLS; BACTERIAL ENTRY; PLASMA-MEMBRANE AB Type 3 secretion systems (T3SSs) of bacterial pathogens translocate bacterial effector proteins that mediate disease into the eukaryotic cytosol. Effectors traverse the plasma membrane through a translocon pore formed by T3SS proteins. In a genome-wide selection, we identified the intermediate filament vimentin as required for infection by the T3SS-dependent pathogen S. flexneri. We found that vimentin is required for efficient T3SS translocation of effectors by S. flexneri and other pathogens that use T3SS, Salmonella enterica serovar Typhimurium and Yersinia pseudotuberculosis. Vimentin and the intestinal epithelial intermediate filament keratin 18 interact with the C-terminus of the Shigella translocon pore protein IpaC. Vimentin and its interaction with IpaC are dispensable for pore formation, but are required for stable docking of S. flexneri to cells; moreover, stable docking triggers effector secretion. These findings establish that stable docking of the bacterium specifically requires intermediate filaments, is a process distinct from pore formation, and is a prerequisite for effector secretion. C1 [Russo, Brian C.; Stamm, Luisa M.; Kim, Caleb M.; Kahoud, Emily; Queiroz, Ana L.; Herrera, Bobby Brooke; Baxt, Leigh A.; Fu, Yang; Molina, Gabriel; Goldberg, Marcia B.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. [Russo, Brian C.; Stamm, Luisa M.; Raaben, Matthijs; Robinson, Lindsey R.; Bose, Sayantan; Baxt, Leigh A.; Whelan, Sean P.; Goldberg, Marcia B.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Mor-Vaknin, Nirit; Markovitz, David M.] Univ Michigan, Div Infect Dis, Dept Internal Med, Med Ctr, Ann Arbor, MI 48109 USA. [Goldberg, Marcia B.] 65 Landsdowne St, Cambridge, MA 02139 USA. [Stamm, Luisa M.] Gilead Sci, Liver Dis Therapeut Area, Foster City, CA 94404 USA. [Raaben, Matthijs] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. [Herrera, Bobby Brooke] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Baxt, Leigh A.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA.; Goldberg, MB (reprint author), Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.; Goldberg, MB (reprint author), 65 Landsdowne St, Cambridge, MA 02139 USA. EM marcia.goldberg@mgh.harvard.edu OI Bose, Sayantan/0000-0003-2397-4740 FU National Institutes of Health (NIH) [RO1 AI081724]; NIH [T32 AI007061, F32 AI092967, F32 AI114162]; New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease; Institute of Chemistry and Cell Biology (ICCB)-Longwood Facility at Harvard Medical School [NIH U54 AI057159]; Coordination for the Improvement of Higher Education Personnel (CAPES) Foundation; Ministry of Education of Brazil, Brasilia-DF, Brazil [70040-020] FX We thank Victor Faundez, Cammie Lesser, Wendy Picking and William Picking, Joan Mecsas, Victoria Auerbuch-Stone, Beth McCormick and Ana Maldonado-Contreras, and Claude Parsot for cell lines, bacterial strains, reagents, technical assistance and protocols, Alexandra Wiscovitch for technical assistance, and Matthew Brown for critical reading of the manuscript. This work was funded by National Institutes of Health (NIH) RO1 AI081724 (to M.B.G.), NIH T32 AI007061 (to B.C.R.), NIH F32 AI092967 (to L.A.B.), NIH F32 AI114162 (to B.C.R.), a career development award through the New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease and the Institute of Chemistry and Cell Biology (ICCB)-Longwood Facility at Harvard Medical School (NIH U54 AI057159, to L.M.S.), and the Coordination for the Improvement of Higher Education Personnel (CAPES) Foundation, Ministry of Education of Brazil, Brasilia-DF, 70040-020, Brazil (to A.L.Q.). NR 69 TC 2 Z9 2 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND EI 2058-5276 J9 NAT MICROBIOL JI NAT. MICROBIOL PD APR PY 2016 VL 1 IS 4 AR 16025 DI 10.1038/NMICROBIOL.2016.25 PG 11 WC Microbiology SC Microbiology GA DW4HY UT WOS:000383605000004 PM 27572444 ER PT J AU Nettiksimmons, J Tranah, G Evans, DS Yokoyama, JS Yaffe, K AF Nettiksimmons, Jasmine Tranah, Gregory Evans, Daniel S. Yokoyama, Jennifer S. Yaffe, Kristine TI Gene-based aggregate SNP associations between candidate AD genes and cognitive decline SO AGE LA English DT Article DE SNP associations; Candidate AD genes; Cognitive decline ID GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; OSTEOPOROTIC FRACTURES; COMMON VARIANTS; CD33; SIGLECS; RISK; EXPRESSION; ROLES; BRAIN AB Single nucleotide polymorphisms (SNPs) in and near ABCA7, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, complement receptor 1 (CR1), EPHA1, EXOC3L2, FERMT2, HLA cluster (DRB5-DQA), INPP5D, MEF2C, MS4A cluster (MS4A3-MS4A6E), NME8, PICALM, PTK2B, SLC24A4, SORL1, and ZCWPW1 have been associated with Alzheimer's disease (AD) in large meta-analyses. We aimed to determine whether established AD-associated genes are associated with longitudinal cognitive decline by examining aggregate variation across these gene regions. In two single-sex cohorts of older, community-dwelling adults, we examined the association between SNPs in previously implicated gene regions and cognitive decline (age-adjusted person-specific cognitive slopes) using a Sequence Kernel Association Test (SKAT). In regions which showed aggregate significance, we examined the univariate association between individual SNPs in the region and cognitive decline. Only two of the original AD-associated SNPs were significantly associated with cognitive decline in our cohorts. We identified significant aggregate-level associations between cognitive decline and the gene regions BIN1, CD33, CELF1, CR1, HLA cluster, and MEF2C in the allfemale cohort and significant associations with ABCA7, HLA cluster, MS4A6E, PICALM, PTK2B, SLC24A4, and SORL1 in the all-male cohort. We also identified a block of eight correlated SNPs in CD33 and several blocks of correlated SNPs in CELF1 that were significantly associated with cognitive decline in univariate analysis in the all-female cohort. C1 [Nettiksimmons, Jasmine] Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,Box VAMC-116H, San Francisco, CA 94121 USA. [Tranah, Gregory] Univ Calif San Francisco, Dept Epidemiol & Biostat, Calif Pacific Med Ctr, Res Inst, Mission Hall Global Hlth & Clin Sci Bldg, San Francisco, CA 94158 USA. [Evans, Daniel S.] Calif Pacific Med Ctr, Res Inst, Mission Hall Global Hlth & Clin Sci Bldg, San Francisco, CA 94158 USA. [Yokoyama, Jennifer S.] Univ Calif San Francisco, Memory & Aging Ctr, Sandler Neurosci Ctr, 675 Nelson Rising Lane,Suite 190, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco Vet Affairs Med Ctr, 4150 Clement St,Box 181, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, 4150 Clement St,Box 181, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco Vet Affairs Med Ctr, 4150 Clement St,Box 181, San Francisco, CA 94121 USA. RP Nettiksimmons, J (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,Box VAMC-116H, San Francisco, CA 94121 USA. EM jasminen@gmail.com; GTranah@psg.ucsf.edu; DEvans@psg.ucsf.edu; jyokoyama@memory.ucsf.edu; kristine.yaffe@ucsf.edu FU National Institutes of Health; National Institute on Aging (NIA) [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Advancing Translational Sciences (NCATS); NIH Roadmap for Medical Research [U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1 TR000128]; NIAMS [RC2 AR058973, R01 AR051124]; National Institute of Aging [K24AG031155]; Larry L. Hillblom Foundation [2012-A-015-FEL]; National Institute on Aging [K01 AG049152]; Diversity Supplement [P50 AG023501]; AFTD Susan Marcus Memorial Fund Clinical Research Grant FX The Study of Osteoporotic Fractures (SOF) is supported by the National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. The Osteoporotic Fractures in Men (MrOS) Study is supported by the National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. The NIAMS provides funding for the MrOS ancillary study "GWAS in MrOS and SOF" under the grant number RC2 AR058973. TheNIAMS provides funding for the MrOS ancillary study "Replication of candidate gene associations and bone strength phenotype in MrOS" under the grant number R01 AR051124. Dr. Yaffe is supported in part by a National Institute of Aging Grant (K24AG031155). Dr. Yokoyama is supported in part by Larry L. Hillblom Foundation 2012-A-015-FEL, National Institute on Aging K01 AG049152 and Diversity Supplement to P50 AG023501, and AFTD Susan Marcus Memorial Fund Clinical Research Grant. NR 33 TC 2 Z9 2 U1 3 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 EI 1574-4647 J9 AGE JI Age PD APR PY 2016 VL 38 IS 2 AR 41 DI 10.1007/s11357-016-9885-2 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA DX9SM UT WOS:000384735400001 PM 27005436 ER PT J AU Plichta, J Coopey, S Specht, M Gadd, M Sullivan, E Roche, C Smith, B Hughes, K AF Plichta, Jennifer Coopey, Suzanne Specht, Michelle Gadd, Michele Sullivan, Erin Roche, Constance Smith, Barbara Hughes, Kevin TI Application of the 2015 ACS and ASBS Screening Mammography Guidelines: Risk Assessment Is Critical for Women Ages 40-44 SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 13-17, 2016 CL Dallas, TX SP Amer Soc Breast Surg C1 [Plichta, Jennifer; Coopey, Suzanne; Specht, Michelle; Gadd, Michele; Sullivan, Erin; Roche, Constance; Smith, Barbara; Hughes, Kevin] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2016 VL 23 SU 3 MA 0445 BP 9 EP 10 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA DX7KU UT WOS:000384566800008 ER PT J AU Plichta, J Coopey, S Gadd, M Specht, M Hughes, K Taghian, A Smith, B AF Plichta, Jennifer Coopey, Suzanne Gadd, Michele Specht, Michelle Hughes, Kevin Taghian, Alphonse Smith, Barbara TI Factors Associated With Recurrence Rates and Long-Term Survival in Women Diagnosed With Breast Cancer Ages 40 and Younger SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 13-17, 2016 CL Dallas, TX SP Amer Soc Breast Surg C1 [Plichta, Jennifer; Coopey, Suzanne; Gadd, Michele; Specht, Michelle; Hughes, Kevin; Taghian, Alphonse; Smith, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2016 VL 23 SU 3 MA 0446 BP 19 EP 21 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA DX7KU UT WOS:000384566800017 ER PT J AU Coopey, S Tang, R Rai, U Plichta, J Colwell, A Gadd, M Specht, M Austen, W Smith, B AF Coopey, Suzanne Tang, Rong Rai, Upahvan Plichta, Jennifer Colwell, Amy Gadd, Michele Specht, Michelle Austen, William Smith, Barbara TI Oncologic Safety of Nipple-Sparing Mastectomy in Women With Breast Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 13-17, 2016 CL Dallas, TX SP Amer Soc Breast Surg C1 [Coopey, Suzanne; Tang, Rong; Rai, Upahvan; Plichta, Jennifer; Colwell, Amy; Gadd, Michele; Specht, Michelle; Austen, William; Smith, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2016 VL 23 SU 3 MA 0292 BP 50 EP 52 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA DX7KU UT WOS:000384566800048 ER PT J AU Plichta, J Reyes, S Frank, E Gonen, M Voci, A Boafo, C Hwang, S Rugo, H Alvarado, M Liu, M Boughey, J Jacobs, L Krontiras, H McGuire, K Storniolo, A Nanda, R Golshan, M Isaacs, C Meszoely, I Van Poznak, C Babiera, G Norton, L Morrow, M Winer, E Wolff, A Hudis, C King, T AF Plichta, Jennifer Reyes, Sylvia Frank, Elizabeth Gonen, Mithat Voci, Amy Boafo, Camilla Hwang, Shelley Rugo, Hope Alvarado, Michael Liu, Minetta Boughey, Judy Jacobs, Lisa Krontiras, Helen McGuire, Kandace Storniolo, Anna Nanda, Rita Golshan, Mehra Isaacs, Claudine Meszoely, Ingrid Van Poznak, Catherine Babiera, Gildy Norton, Larry Morrow, Monica Winer, Eric Wolff, Antonio Hudis, Clifford King, Tari TI Factors Associated With the Decision to Pursue Elective Surgery Among Women Enrolled in TBCRC013: A Prospective Registry of Surgery in Patients Presenting With Stage IV Breast Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 13-17, 2016 CL Dallas, TX SP Amer Soc Breast Surg C1 [Plichta, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reyes, Sylvia; Gonen, Mithat; Boafo, Camilla; Norton, Larry; Morrow, Monica; Hudis, Clifford; King, Tari] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Frank, Elizabeth; Golshan, Mehra; Winer, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Voci, Amy] John Wayne Canc Inst, Santa Monica, CA USA. [Hwang, Shelley] Duke Univ, Durham, NC USA. [Rugo, Hope] UCSF, San Francisco, CA USA. [Alvarado, Michael] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Liu, Minetta; Isaacs, Claudine] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Boughey, Judy] Mayo Clin, Rochester, MN USA. [Jacobs, Lisa; Wolff, Antonio] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Krontiras, Helen] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [McGuire, Kandace] Univ N Carolina, Chapel Hill, NC USA. [Storniolo, Anna] Indiana Univ, Indianapolis, IN 46204 USA. [Nanda, Rita] Univ Chicago, Chicago, IL 60637 USA. [Meszoely, Ingrid] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Van Poznak, Catherine] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Babiera, Gildy] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2016 VL 23 SU 3 MA 0233 BP 131 EP 133 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA DX7KU UT WOS:000384566800129 ER PT J AU Rai, U Tang, R Plichta, J Merrill, A Rice-Stitt, T Gadd, M Specht, M Brachtel, E Smith, B AF Rai, Upahvan Tang, Rong Plichta, Jennifer Merrill, Andrea Rice-Stitt, Travis Gadd, Michele Specht, Michelle Brachtel, Elena Smith, Barbara TI Feasibility of the LUM Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Lumpectomy Cavity Margins SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 13-17, 2016 CL Dallas, TX SP Amer Soc Breast Surg C1 [Rai, Upahvan; Tang, Rong; Plichta, Jennifer; Merrill, Andrea; Rice-Stitt, Travis; Gadd, Michele; Specht, Michelle; Brachtel, Elena] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2016 VL 23 SU 3 MA 0296 BP 135 EP 136 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA DX7KU UT WOS:000384566800132 ER PT J AU Tang, R Coopey, S Plichta, J Rai, U Colwell, A Gadd, M Specht, M Austen, W Smith, B AF Tang, Rong Coopey, Suzanne Plichta, Jennifer Rai, Upahvan Colwell, Amy Gadd, Michele Specht, Michelle Austen, William Smith, Barbara TI Nipple Changes During and After Pregnancy in Women Who Have Undergone Nipple-Sparing Mastectomy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 13-17, 2016 CL Dallas, TX SP Amer Soc Breast Surg C1 [Tang, Rong; Coopey, Suzanne; Plichta, Jennifer; Rai, Upahvan; Colwell, Amy; Gadd, Michele; Specht, Michelle; Austen, William; Smith, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2016 VL 23 SU 3 MA 0355 BP 152 EP 153 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA DX7KU UT WOS:000384566800150 ER PT J AU Tang, R Griffin, M Saksena, M Coopey, S DiCorpo, D Gadd, M Specht, M Brachtel, E Michaelson, J Smith, B AF Tang, Rong Griffin, Molly Saksena, Mansi Coopey, Suzanne DiCorpo, Daniel Gadd, Michele Specht, Michelle Brachtel, Elena Michaelson, James Smith, Barbara TI Evaluation of Shaved Cavity Margins with Microcomputed Tomography-A Novel Method for Predicting Lumpectomy Margin Status Intraoperatively SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 13-17, 2016 CL Dallas, TX SP Amer Soc Breast Surg C1 [Tang, Rong; Griffin, Molly; Saksena, Mansi; Coopey, Suzanne; DiCorpo, Daniel; Gadd, Michele; Specht, Michelle; Brachtel, Elena; Michaelson, James; Smith, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2016 VL 23 SU 3 MA 0361 BP 154 EP 155 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA DX7KU UT WOS:000384566800151 ER PT J AU Yachie, N Petsalaki, E Mellor, JC Weile, J Jacob, Y Verby, M Ozturk, SB Li, SY Cote, AG Mosca, R Knapp, JJ Ko, M Yu, A Gebbia, M Sahni, N Yi, S Tyagi, T Sheykhkarimli, D Roth, JF Wong, C Musa, L Snider, J Liu, YC Yu, HY Braun, P Stagljar, I Hao, T Calderwood, MA Pelletier, L Aloy, P Hill, DE Vidal, M Roth, FP AF Yachie, Nozomu Petsalaki, Evangelia Mellor, Joseph C. Weile, Jochen Jacob, Yves Verby, Marta Ozturk, Sedide B. Li, Siyang Cote, Atina G. Mosca, Roberto Knapp, Jennifer J. Ko, Minjeong Yu, Analyn Gebbia, Marinella Sahni, Nidhi Yi, Song Tyagi, Tanya Sheykhkarimli, Dayag Roth, Jonathan F. Wong, Cassandra Musa, Louai Snider, Jamie Liu, Yi-Chun Yu, Haiyuan Braun, Pascal Stagljar, Igor Hao, Tong Calderwood, Michael A. Pelletier, Laurence Aloy, Patrick Hill, David E. Vidal, Marc Roth, Frederick P. TI Pooled-matrix protein interaction screens using Barcode Fusion Genetics SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE DNA barcode; interactome; next-generation sequencing; protein interaction; yeast two-hybrid ID OPEN READING FRAMES; INTERACTION NETWORK; TRANSCRIPTIONAL ACTIVATION; HUMAN-CELLS; SCALE MAP; YEAST; COMPLEX; EXPRESSION; GENERATION; SELECTION AB High-throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will require screening at substantially larger scales with many complementary assays, requiring further efficiency gains in proteome-scale interaction mapping. Here, we report Barcode Fusion Genetics-Yeast Two-Hybrid (BFG-Y2H), by which a full matrix of protein pairs can be screened in a single multiplexed strain pool. BFG-Y2H uses Cre recombination to fuse DNA barcodes from distinct plasmids, generating chimeric protein-pair barcodes that can be quantified via next-generation sequencing. We applied BFG-Y2H to four different matrices ranging in scale from similar to 25 K to 2.5 M protein pairs. The results show that BFG-Y2H increases the efficiency of protein matrix screening, with quality that is on par with state-of-the-art Y2H methods. C1 [Yachie, Nozomu; Petsalaki, Evangelia; Mellor, Joseph C.; Weile, Jochen; Verby, Marta; Ozturk, Sedide B.; Li, Siyang; Cote, Atina G.; Knapp, Jennifer J.; Ko, Minjeong; Yu, Analyn; Gebbia, Marinella; Tyagi, Tanya; Sheykhkarimli, Dayag; Roth, Jonathan F.; Wong, Cassandra; Musa, Louai; Snider, Jamie; Liu, Yi-Chun; Stagljar, Igor; Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON, Canada. [Yachie, Nozomu; Petsalaki, Evangelia; Mellor, Joseph C.; Weile, Jochen; Verby, Marta; Ozturk, Sedide B.; Li, Siyang; Cote, Atina G.; Knapp, Jennifer J.; Ko, Minjeong; Yu, Analyn; Gebbia, Marinella; Tyagi, Tanya; Sheykhkarimli, Dayag; Roth, Jonathan F.; Wong, Cassandra; Musa, Louai; Pelletier, Laurence; Roth, Frederick P.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada. [Yachie, Nozomu] Univ Tokyo, Res Ctr Adv Sci & Technol, Synthet Biol Div, Tokyo, Japan. [Yachie, Nozomu] Keio Univ, Inst Adv Biosci, Tsuruoka, Yamagata, Japan. [Yachie, Nozomu] Japan Sci & Technol Agcy JST, PRESTO, Tokyo, Japan. [Weile, Jochen; Sheykhkarimli, Dayag; Roth, Jonathan F.; Stagljar, Igor; Pelletier, Laurence; Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Jacob, Yves] Inst Pasteur, Unite Genet Mol Virus ARN, Dept Virol, Paris, France. [Mosca, Roberto; Aloy, Patrick] Inst Res Biomed IRB Barcelona, Joint IRB BSC Program Computat Biol, Barcelona, Spain. [Sahni, Nidhi; Yi, Song; Braun, Pascal; Hao, Tong; Calderwood, Michael A.; Hill, David E.; Vidal, Marc; Roth, Frederick P.] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Sahni, Nidhi; Yi, Song; Braun, Pascal; Hao, Tong; Calderwood, Michael A.; Hill, David E.; Vidal, Marc; Roth, Frederick P.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Sahni, Nidhi; Yi, Song; Braun, Pascal; Hao, Tong; Calderwood, Michael A.; Hill, David E.; Vidal, Marc] Harvard Med Sch, Dept Genet, Boston, MA USA. [Yu, Haiyuan] Cornell Univ, Weill Inst Cell & Mol Biol, Ithaca, NY USA. [Braun, Pascal] Tech Univ Munich, Dept Plant Syst Biol, Wissensch Zentrum Weihenstephan, Freising Weihenstephan, Germany. [Aloy, Patrick] ICREA, Barcelona, Spain. [Roth, Frederick P.] Canadian Inst Adv Res, Toronto, ON, Canada. [Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada. [Sahni, Nidhi] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. RP Yachie, N; Roth, FP (reprint author), Univ Toronto, Donnelly Ctr, Toronto, ON, Canada.; Yachie, N; Roth, FP (reprint author), Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.; Yachie, N (reprint author), Univ Tokyo, Res Ctr Adv Sci & Technol, Synthet Biol Div, Tokyo, Japan.; Yachie, N (reprint author), Keio Univ, Inst Adv Biosci, Tsuruoka, Yamagata, Japan.; Yachie, N (reprint author), Japan Sci & Technol Agcy JST, PRESTO, Tokyo, Japan.; Roth, FP (reprint author), Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.; Roth, FP (reprint author), Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA.; Roth, FP (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.; Roth, FP (reprint author), Canadian Inst Adv Res, Toronto, ON, Canada.; Roth, FP (reprint author), Univ Toronto, Dept Comp Sci, Toronto, ON, Canada. EM yachie@synbiol.rcast.u-tokyo.ac.jp; fritz.roth@utoronto.ca OI Petsalaki, Evangelia/0000-0002-8294-2995; Falter-Braun, Pascal/0000-0003-2012-6746; Roth, Frederick/0000-0002-6628-649X FU Krembil Foundation; Avon Foundation; Ontario Research Fund; Canada Excellence Research Chairs Program; US National Institutes of Health (NIH) grants [HG001715, HG004233]; JSPS Fellowship (Research Abroad); Japan Society for the Promotion of Science; Banting Postdoctoral Fellowship; National Sciences and Engineering Research Council of Canada; Japan Science and Technology Agency (JST) PRESTO grant; JSPS [15K18466]; Astellas Foundation for Research on Metabolic Disorders; Shimazu Foundation; Life Science Foundation of Japan; Nestle Nutrition Council, Japan; Canadian Institutes of Health Research (CIHR) [MOP-123468, MOP-130507]; CQDM/OCE Explore Program; Ontario Genomics Institute; Canadian Cystic Fibrosis Foundation; Canadian Cancer Society; Pancreatic Cancer Canada; University Health Network; Genome Canada DIG1 program; Genome Canada DIG2 program FX This work was supported by the Krembil Foundation (F.P.R. and L.P,), the Avon Foundation (F.P.R.), the Ontario Research Fund (F.P.R. and L.P.), the Canada Excellence Research Chairs Program (F.P.R.), and by US National Institutes of Health (NIH) grants HG001715 (M.Vidal, D.E.H and F.P.R.) and HG004233 (a "Centers of Excellence in Genomic Science" award; M.Vidal and F.P.R.). N.Y. was supported by a JSPS Fellowship (Research Abroad), Japan Society for the Promotion of Science, a Banting Postdoctoral Fellowship, National Sciences and Engineering Research Council of Canada, Japan Science and Technology Agency (JST) PRESTO grant, JSPS grant 15K18466, Astellas Foundation for Research on Metabolic Disorders, Shimazu Foundation, Life Science Foundation of Japan, and by Nestle Nutrition Council, Japan. L.P. was supported by Canadian Institutes of Health Research (CIHR) grants MOP-123468 and MOP-130507. I.S. was supported by grants from the CQDM/OCE Explore Program, Ontario Genomics Institute, Canadian Cystic Fibrosis Foundation, Canadian Cancer Society, Pancreatic Cancer Canada, University Health Network and Genome Canada DIG1 and DIG2 programs. Sequencing was performed at the Donnelly Sequencing Centre, University of Toronto. We are grateful for early discussions with J. Weissman, for Y-strains from C. Boone (University of Toronto), and for advice and assistance from B. Andrews, M. Chee, G. Church, A.-C. Gingras, L. Heisler, J. Liu, N. Mohammad, L. Ng, C. Nislow, A. Rosebrock, K. Salehi-Ashtiani, B. Steen, and D. Torti; members of the Roth Lab, especially C. Cheung, A. Karkhanina, S. Sun, Y. Suzuki, M. Tasan and J. Weile; members of the DFCI Center for Cancer Systems Biology (CCSB); and members of the Pelletier laboratory, especially M. Bashkurov, D. Comartin, J. Goncalves, S. Lawo, B. Mojarad, and C. Yeh. NR 72 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD APR PY 2016 VL 12 IS 4 AR 863 DI 10.15252/msb.20156660 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DX9JK UT WOS:000384710700002 PM 27107012 ER PT J AU Zhong, Q Pevzner, SJ Hao, T Wang, Y Mosca, R Menche, J Taipale, M Tasan, M Fan, CY Yang, XP Haley, P Murray, RR Mer, F Gebreab, F Tam, S MacWilliams, A Dricot, A Reichert, P Santhanam, B Ghamsari, L Calderwood, MA Rolland, T Charloteaux, B Lindquist, S Barabasi, AL Hill, DE Aloy, P Cusick, ME Xia, Y Roth, FP Vidal, M AF Zhong, Quan Pevzner, Samuel J. Hao, Tong Wang, Yang Mosca, Roberto Menche, Jorg Taipale, Mikko Tasan, Murat Fan, Changyu Yang, Xinping Haley, Patrick Murray, Ryan R. Mer, Flora Gebreab, Fana Tam, Stanley MacWilliams, Andrew Dricot, Amelie Reichert, Patrick Santhanam, Balaji Ghamsari, Lila Calderwood, Michael A. Rolland, Thomas Charloteaux, Benoit Lindquist, Susan Barabasi, Albert-Laszlo Hill, David E. Aloy, Patrick Cusick, Michael E. Xia, Yu Roth, Frederick P. Vidal, Marc TI An inter-species protein-protein interaction network across vast evolutionary distance SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE Cross-species complementation; Network evolution; Selection ID MORPHOLOGICAL EVOLUTION; ORTHOLOGY ANALYSIS; HUMAN-DISEASE; SCALE MAP; EVO-DEVO; COMPLEXITY; GENE; DROSOPHILA; YEAST; DISORDER AB In cellular systems, biophysical interactions between macromolecules underlie a complex web of functional interactions. How biophysical and functional networks are coordinated, whether all biophysical interactions correspond to functional interactions, and how such biophysical-versus-functional network coordination is shaped by evolutionary forces are all largely unanswered questions. Here, we investigate these questions using an "interinteractome" approach. We systematically probed the yeast and human proteomes for interactions between proteins from these two species and functionally characterized the resulting inter-interactome network. After a billion years of evolutionary divergence, the yeast and human proteomes are still capable of forming a biophysical network with properties that resemble those of intra-species networks. Although substantially reduced relative to intra-species networks, the levels of functional overlap in the yeast-human inter-interactome network uncover significant remnants of co-functionality widely preserved in the two proteomes beyond human-yeast homologs. Our data support evolutionary selection against biophysical interactions between proteins with little or no co-functionality. Such non-functional interactions, however, represent a reservoir from which nascent functional interactions may arise. C1 [Zhong, Quan; Pevzner, Samuel J.; Hao, Tong; Wang, Yang; Menche, Jorg; Tasan, Murat; Fan, Changyu; Yang, Xinping; Haley, Patrick; Murray, Ryan R.; Mer, Flora; Gebreab, Fana; Tam, Stanley; MacWilliams, Andrew; Dricot, Amelie; Reichert, Patrick; Santhanam, Balaji; Ghamsari, Lila; Calderwood, Michael A.; Rolland, Thomas; Charloteaux, Benoit; Barabasi, Albert-Laszlo; Hill, David E.; Cusick, Michael E.; Xia, Yu; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Zhong, Quan; Pevzner, Samuel J.; Hao, Tong; Wang, Yang; Menche, Jorg; Tasan, Murat; Fan, Changyu; Yang, Xinping; Haley, Patrick; Murray, Ryan R.; Mer, Flora; Gebreab, Fana; Tam, Stanley; MacWilliams, Andrew; Dricot, Amelie; Reichert, Patrick; Santhanam, Balaji; Ghamsari, Lila; Calderwood, Michael A.; Rolland, Thomas; Charloteaux, Benoit; Barabasi, Albert-Laszlo; Hill, David E.; Cusick, Michael E.; Xia, Yu; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Zhong, Quan; Pevzner, Samuel J.; Hao, Tong; Wang, Yang; Fan, Changyu; Yang, Xinping; Haley, Patrick; Murray, Ryan R.; Mer, Flora; Gebreab, Fana; Tam, Stanley; MacWilliams, Andrew; Dricot, Amelie; Reichert, Patrick; Santhanam, Balaji; Ghamsari, Lila; Calderwood, Michael A.; Rolland, Thomas; Charloteaux, Benoit; Hill, David E.; Cusick, Michael E.; Vidal, Marc] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. [Zhong, Quan] Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA. [Pevzner, Samuel J.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Pevzner, Samuel J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Mosca, Roberto; Aloy, Patrick] Barcelona Inst Sci & Technol, Joint IRB BSC CRG Program Computat Biol, Inst Res Biomed IRB Barcelona, Barcelona, Catalonia, Spain. [Menche, Jorg; Barabasi, Albert-Laszlo] Northeastern Univ, CCNR, Boston, MA 02115 USA. [Menche, Jorg; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Taipale, Mikko; Lindquist, Susan] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. [Tasan, Murat; Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Tasan, Murat; Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada. [Tasan, Murat; Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON, Canada. [Tasan, Murat; Roth, Frederick P.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada. [Lindquist, Susan] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Lindquist, Susan] MIT, Howard Hughes Med Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Barabasi, Albert-Laszlo] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Aloy, Patrick] ICREA, Barcelona, Spain. [Xia, Yu] McGill Univ, Dept Bioengn, Montreal, PQ, Canada. [Roth, Frederick P.] Canadian Inst Adv Res, Toronto, ON, Canada. RP Zhong, Q; Xia, Y; Roth, FP; Vidal, M (reprint author), Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA.; Zhong, Q; Xia, Y; Roth, FP; Vidal, M (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.; Zhong, Q; Vidal, M (reprint author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.; Zhong, Q (reprint author), Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA.; Roth, FP (reprint author), Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.; Roth, FP (reprint author), Univ Toronto, Dept Comp Sci, Toronto, ON, Canada.; Roth, FP (reprint author), Univ Toronto, Donnelly Ctr, Toronto, ON, Canada.; Roth, FP (reprint author), Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.; Xia, Y (reprint author), McGill Univ, Dept Bioengn, Montreal, PQ, Canada.; Roth, FP (reprint author), Canadian Inst Adv Res, Toronto, ON, Canada. EM quan.zhong@wright.edu; brandon.xia@mcgill.ca; fritz.roth@utoronto.ca; marc_vidal@dfci.harvard.edu RI Menche, Jorg/G-3994-2015; OI Menche, Jorg/0000-0002-1583-6404; Taipale, Mikko/0000-0003-3811-1761; Xia, Yu/0000-0002-5596-5518; Roth, Frederick/0000-0002-6628-649X FU National Human Genome Research Institute (NHGRI) [R01-HG006061, R01-HG001715]; National Science Foundation (NSF) [CCF-1219007]; Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2014-03892]; Canada Foundation for Innovation (CFI) [JELF-33732]; Canada Research Chairs Program; Canada Excellence Research Chairs Program; Krembil Foundation; Ontario Research Fund FX The authors would like to thank Y. Jacob, J. De Las Rivas, A.J.M. Walhout, and members of the Center for Cancer Systems Biology (CCSB) at the Dana-Farber Cancer Institute for critical reading of the manuscript. This research was supported by National Human Genome Research Institute (NHGRI) grants R01-HG006061 awarded to M.V., D.E.H., and M.E.C. and R01-HG001715 awarded to M.V., D.E.H., and F.P.R. Y.X. receives support from National Science Foundation (NSF) grant CCF-1219007, Natural Sciences and Engineering Research Council of Canada (NSERC) grant RGPIN-2014-03892, Canada Foundation for Innovation (CFI) grant JELF-33732, and Canada Research Chairs Program. F.P.R. received support from the Canada Excellence Research Chairs Program, the Krembil Foundation, and the Ontario Research Fund. M.V. is a Chercheur Qualifie Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation). NR 85 TC 1 Z9 1 U1 8 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD APR PY 2016 VL 12 IS 4 AR 865 DI 10.15252/msb.20156484 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DX9JK UT WOS:000384710700004 PM 27107014 ER PT J AU Agboola, S Palacholla, RS Centi, A Kvedar, J Jethwani, K AF Agboola, Stephen Palacholla, Ramya Sita Centi, Amanda Kvedar, Joseph Jethwani, Kamal TI A Multimodal mHealth Intervention (FeatForward) to Improve Physical Activity Behavior in Patients with High Cardiometabolic Risk Factors: Rationale and Protocol for a Randomized Controlled Trial SO JMIR RESEARCH PROTOCOLS LA English DT Article DE mobile app; physical activity; randomized clinical trial; type 2 diabetes mellitus; exercise; cardiometabolic risk factors ID HEALTH; ASSOCIATIONS; PREVENTION; FITNESS AB Background: Physical inactivity is one of the leading risk factors contributing to the rising rates of chronic diseases and has been associated with deleterious health outcomes in patients with chronic disease conditions. We developed a mobile phone app, FeatForward, to increase the level of physical activity in patients with cardiometabolic risk (CMR) factors. This intervention is expected to result in an overall improvement in patient health outcomes. Objective: The objective of this study is to evaluate the effect of a mobile phone-based app, FeatForward, on physical activity levels and other CMR factors in patients with chronic conditions. Methods: The study will be implemented as a 2-arm randomized controlled trial with 300 adult patients with chronic conditions over a 6-month follow-up period. Participants will be assigned to either the intervention group receiving the FeatForward app and standard care versus a control group who will receive only usual care. The difference in physical activity levels between the control group and intervention group will be measured as the primary outcome. We will also evaluate the effect of this intervention on secondary measures including clinical outcome changes in global CMR factors (glycated hemoglobin, fasting blood glucose, blood pressure, waist circumference, Serum lipids, C-reactive protein), health-related quality of life, health care usage, including attendance of scheduled clinic visits and hospitalizations, usability, and satisfaction, participant engagement with the FeatForward app, physician engagement with physician portal, and willingness to engage in physical activity. Instruments that will be used in evaluating secondary outcomes include the Short-Form (SF)-12, app usability and satisfaction questionnaires, physician satisfaction questionnaire. The intention-to-treat approach will be used to evaluate outcomes. All outcomes will be measured longitudinally at baseline, midpoint (3 months), and 6 months. Our primary outcome, physical activity, will be assessed by mixed-model analysis of variance with intervention assignment as between-group factor and time as within-subject factor. A similar approach will be used to analyze continuous secondary outcomes while categorical outcomes will be analyzed by chi-square test. Results: The study is still in progress and we hope to have the results by the end of 2016. Conclusions: The mobile phone-based app, FeatForward, could lead to significant improvements in physical activity and other CMR factors in patients. C1 [Agboola, Stephen; Palacholla, Ramya Sita; Centi, Amanda; Kvedar, Joseph; Jethwani, Kamal] Ctr Connected Hlth, 25 New Chardon St, Boston, MA 02114 USA. [Agboola, Stephen; Palacholla, Ramya Sita; Kvedar, Joseph; Jethwani, Kamal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Agboola, Stephen; Palacholla, Ramya Sita; Kvedar, Joseph; Jethwani, Kamal] Harvard Med Sch, Boston, MA USA. RP Agboola, S (reprint author), Ctr Connected Hlth, 25 New Chardon St, Boston, MA 02114 USA. EM sagboola@partners.org RI Emchi, Karma/Q-1952-2016; OI palacholla, ramya/0000-0001-5054-7619 NR 18 TC 0 Z9 0 U1 9 U2 9 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1929-0748 J9 JMIR RES PROTOC JI JMIR RES. Protoc. PD APR-JUN PY 2016 VL 5 IS 2 AR e84 DI 10.2196/resprot.5489 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DT1AH UT WOS:000381213600005 PM 27174783 ER PT J AU Schlosser, D Campellone, T Kim, D Truong, B Vergani, S Ward, C Vinogradov, S AF Schlosser, Danielle Campellone, Timothy Kim, Daniel Truong, Brandy Vergani, Silvia Ward, Charlie Vinogradov, Sophia TI Feasibility of PRIME: A Cognitive Neuroscience-Informed Mobile App Intervention to Enhance Motivated Behavior and Improve Quality of Life in Recent Onset Schizophrenia SO JMIR RESEARCH PROTOCOLS LA English DT Article DE schizophrenia; mobile app; smartphone; motivation; technology-based intervention; social networking; coaching; negative symptoms; quality of life ID NEGATIVE SYMPTOMS; ENVIRONMENTAL SUPPORTS; PHYSICAL-ACTIVITY; RECOVERY; OUTCOMES; PEOPLE; METAANALYSIS; OUTPATIENTS; DISORDERS; DEFICITS AB Background: Despite improvements in treating psychosis, schizophrenia remains a chronic and debilitating disorder that affects approximately 1% of the US population and costs society more than depression, dementia, and other medical illnesses across most of the lifespan. Improving functioning early in the course of illness could have significant implications for long-term outcome of individuals with schizophrenia. Yet, current gold-standard treatments do not lead to clinically meaningful improvements in outcome, partly due to the inherent challenges of treating a population with significant cognitive and motivational impairments. The rise of technology presents an opportunity to develop novel treatments that may circumvent the motivational and cognitive challenges observed in schizophrenia. Objective: The purpose of this study was two-fold: (1) to evaluate the feasibility and acceptability of implementing a Personalized Real-Time Intervention for Motivation Enhancement (PRIME), a mobile app intervention designed to target reward-processing impairments, enhance motivation, and thereby improve quality of life in recent onset schizophrenia, and (2) evaluate the empirical benefits of using an iterative, user-centered design (UCD) process. Methods: We conducted two design workshops with 15 key stakeholders, followed by a series of in-depth interviews in collaboration with IDEO, a design and innovation firm. The UCD approach ultimately resulted in the first iteration of PRIME, which was evaluated by 10 RO participants. Results from the Stage 1 participants were then used to guide the next iteration that is currently being evaluated in an ongoing RCT. Participants in both phases were encouraged to use the app daily with a minimum frequency of 1/week over a 12-week period. Results: The UCD process resulted in the following feature set: (1) delivery of text message (short message service, SMS)-based motivational coaching from trained therapists, (2) individualized goal setting in prognostically important psychosocial domains, (3) social networking via direct peer-to-peer messaging, and (4) community "moments feed" to capture and reinforce rewarding experiences and goal achievements. Users preferred an experience that highlighted several of the principles of self-determination theory, including the desire for more control of their future (autonomy and competence) and an approach that helps them improve existing relationships (relatedness). IDEO, also recommended an approach that was casual, friendly, and nonstigmatizing, which is in line with the recovery model of psychosis. After 12-weeks of using PRIME, participants used the app, on average, every other day, were actively engaged with its various features each time they logged in and retention and satisfaction was high (20/20, 100% retention, high satisfaction ratings). The iterative design process lead to a 2- to 3-fold increase in engagement from Stage 1 to Stage 2 in almost each aspect of the platform. Conclusions: These results indicate that the neuroscience-informed mobile app, PRIME, is a feasible and acceptable intervention for young people with schizophrenia. C1 [Schlosser, Danielle; Kim, Daniel; Truong, Brandy; Ward, Charlie; Vinogradov, Sophia] Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94134 USA. [Campellone, Timothy] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Vergani, Silvia] IDEO, Palo Alto, CA USA. [Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. RP Schlosser, D (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94134 USA. EM danielle.schlosser@ucsf.edu RI Emchi, Karma/Q-1952-2016; OI Schlosser, Danielle/0000-0001-7652-0924 FU NCATS NIH HHS [UL1 TR000004]; NIMH NIH HHS [K23 MH097795, R34 MH100399] NR 41 TC 0 Z9 0 U1 12 U2 14 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1929-0748 J9 JMIR RES PROTOC JI JMIR RES. Protoc. PD APR-JUN PY 2016 VL 5 IS 2 AR e77 DI 10.2196/resprot.5450 PG 13 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DT1AH UT WOS:000381213600043 PM 27125771 ER PT J AU Li, L Shelton, RC Chassan, RA Hammond, JC Gower, BA Garvey, TW AF Li, Li Shelton, Richard Charles Chassan, Rachel Ann Hammond, John Charles Gower, Barbara Ann Garvey, Timothy W. TI Impact of Major Depressive Disorder on Prediabetes by Impairing Insulin Sensitivity SO JOURNAL OF DIABETES & METABOLISM LA English DT Article DE Insulin sensitivity; Prediabetes; Atherosclerosis; Phosphorylation; Cardiovascular diseases; Glucose tolerance test ID TYPE-2 DIABETES-MELLITUS; ORAL GLUCOSE-TOLERANCE; RISK-FACTOR; PLASMA-GLUCOSE; DSM-IV; RESISTANCE; METABOLISM; ADIPOSITY; DISEASE; HEALTH AB Reports regarding the associations between major depressive disorder (MDD) and diabetes remain heterogeneous. Our aim was to investigate whether glucose homeostasis and insulin sensitivity were impaired in the MDD patients and its mechanisms. A total of 30 patients with MDD and 30 matched controls were recruited. The oral glucose tolerance test and dual-energy X-ray absorptiometry scan were performed in each participant. Insulin signaling in postmortem brain tissues from other depressive patients and controls (obtained from Alabama brain bank) was examined. Insulin sensitivity was reduced substantially in the MDD patients, however, the fasting and 2-h glucose concentrations remained within the normal range through compensatory insulin secretion. Despite increased insulin secretion, 1-h glucose concentrations in the MDD patients were significantly elevated compared with the controls. MDD patients had greater visceral fat mass but lower adiponectin levels compared with the controls. Furthermore, phosphorylated-AKT levels in insulin signaling were decreased in postmortem brain tissues in patients with MDD. These results suggest that MDD patients are at a greater risk for diabetes due to decreased insulin sensitivity, reduced disposition index, and impaired glucose tolerance as manifested by elevated 1-h glucose concentrations following an oral glucose challenge. Mechanistic studies reveal that decreased insulin sensitivity is associated with increased visceral fat mass, lower adiponectin levels and impaired insulin action in postmortem brain tissues in the MDD patients. Our findings emphasize the importance of screening depressive patients to identify susceptible individuals for developing future diabetes with the hope of improving their health outcomes. C1 [Li, Li; Shelton, Richard Charles; Chassan, Rachel Ann; Hammond, John Charles] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, 1720 Univ Blvd, Birmingham, AL 35294 USA. [Gower, Barbara Ann; Garvey, Timothy W.] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, Timothy W.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Li, L (reprint author), Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, 1720 Univ Blvd, Birmingham, AL 35294 USA. EM lili978@uab.edu NR 30 TC 0 Z9 0 U1 3 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2155-6156 J9 J DIABETES METAB JI J. Diabetes Metab. PD APR PY 2016 VL 7 IS 4 AR UNSP 664 DI 10.4172/2155-6156.1000664 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DX6BB UT WOS:000384466000003 ER PT J AU Ostergaard, L Sakadzic, S AF Ostergaard, Leif Sakadzic, Sava TI Emerging research areas in need of neurophotonics: report from the 2014 Aarhus Capillary Transit Time Heterogeneity (CTH) meeting SO NEUROPHOTONICS LA English DT Editorial Material ID OXYGEN-TRANSPORT; TISSUE C1 [Ostergaard, Leif] Aarhus Univ, Dept Neuroradiol, Ctr Functionally Integrat Neurosci, Aarhus Univ Hosp, Norrebrogade 44,Bldg 10G, DK-8000 Aarhus C, Denmark. [Sakadzic, Sava] Harvard Med Sch, Massachusetts Gen Hosp, Opt Div, Martinos Ctr Biomed Imaging,Radiol, 149 13th St,Room 2301, Charlestown, MA 02129 USA. RP Ostergaard, L (reprint author), Aarhus Univ, Dept Neuroradiol, Ctr Functionally Integrat Neurosci, Aarhus Univ Hosp, Norrebrogade 44,Bldg 10G, DK-8000 Aarhus C, Denmark. EM leif@cfin.au.dk; sava.sakadzic@mgh.harvard.edu RI Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 2329-423X EI 2329-4248 J9 NEUROPHOTONICS JI Neurophotonics PD APR-JUN PY 2016 VL 3 IS 2 AR 020401 DI 10.1117/1.NPh.3.2.020401 PG 3 WC Neurosciences; Optics SC Neurosciences & Neurology; Optics GA DV9IH UT WOS:000383253600002 ER PT J AU Hermayer, KL AF Hermayer, Kathie L. TI The Diabetes Initiative of South Carolina Celebrates Over 20 Years of Professional Diabetes Education SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Diabetes mellitus; South Carolina; Symposium; Education; Program AB Background: Diabetes is a major public health problem in South Carolina; however, the Diabetes Initiative of South Carolina (DSC) provides a realistic mechanism to address issues on a statewide basis. Methods: The Diabetes Center of Excellence in the DSC provides oversight for developing and supervising professional education programs for health care workers of all types in South Carolina to increase their knowledge and ability to care for people with diabetes. The DSC has developed many programs for the education of a variety of health professionals about diabetes and its complications. Results: The DSC has sponsored 21 Annual Diabetes Fall Symposia for primary health care professionals featuring education regarding many aspects of diabetes mellitus. The intent of the program is to enhance the lifelong learning process of physicians, advanced practice providers, nurses, pharmacists, dietitians, laboratorians and other health care professionals, by providing educational opportunities and to advance the quality and safety of patient care. The symposium is an annual 2-day statewide program that supplies both a comprehensive diabetes management update to all primary care professionals and an opportunity for attendees to obtain continuing education credits at a low cost. Conclusion: The overarching goal of the DSC is that the programs it sponsors and the development of new targeted initiatives will lead to continuous improvements in the care of people at risk and with diabetes along with a decrease in morbidity, mortality and costs of diabetes and its complications in South Carolina and elsewhere. C1 [Hermayer, Kathie L.] Med Univ South Carolina, Qual Dept, Charleston, SC USA. [Hermayer, Kathie L.] Med Univ South Carolina, Dept Med, Div Endocrinol, Charleston, SC USA. [Hermayer, Kathie L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Hermayer, KL (reprint author), Med Univ South Carolina, 96 Jonathan Lucas St,CSB 938,MSC 624, Charleston, SC 29425 USA. EM hermayer@musc.edu NR 1 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 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD APR PY 2016 VL 351 IS 4 BP 325 EP 326 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DV1FJ UT WOS:000382665400001 PM 27079336 ER PT J AU Walker, RJ Williams, JS Egede, LE AF Walker, Rebekah J. Williams, Joni Strom Egede, Leonard E. TI Influence of Race, Ethnicity and Social Determinants of Health on Diabetes Outcomes SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Social determinants of health; Diabetes; Health disparities; Psychosocial factors; Neighborhood factors ID SELF-CARE BEHAVIORS; NUTRITION EXAMINATION SURVEY; IMPROVE GLYCEMIC CONTROL; HISPANIC WHITE ADULTS; NEIGHBORHOOD FACTORS; UNITED-STATES; CARDIOVASCULAR-DISEASE; SOCIOECONOMIC-STATUS; RACIAL DISPARITIES; AFRICAN-AMERICANS AB Background: There is strong evidence that race, ethnicity and social determinants of health significantly influence outcomes for patients with diabetes. A better understanding of the mechanisms of these relationships or associations would improve development of cost-effective, culturally tailored programs for patients with diabetes. Methods: This article reviews the current state of the literature on the influence of race and ethnicity and social determinants of health on process of care, quality of care and outcomes for diabetes, with particular emphasis on the rural South to give an overview of the state of the literature. Results: The literature review shows that racial or ethnic differences in the clinical outcomes for diabetes, including glycemic, blood pressure (BP) and lipid control, continue to persist. In addition, the literature review shows that the role of social determinants of health on outcomes, and the possible role these determinants play in disparities have largely been ignored. Psychosocial factors, such as self-efficacy, depression, social support and perceived stress, show consistent associations with self-care, quality of life and glycemic control. Neighborhood factors, such as food insecurity, social cohesion and neighborhood esthetics have been associated with glycemic control. Perceived discrimination has also been associated with self-care and the psychological component of quality of life. Conclusion: Healthcare professionals need to be skilled in assessing social determinants of health and taking them into consideration in clinical care. In addition, more research is needed to identify the separate and combined influence of race and ethnicity and social determinants of health on process of care, quality of care and outcomes in diabetes, especially in the South, where the burden of disease is particularly high. C1 [Walker, Rebekah J.; Williams, Joni Strom; Egede, Leonard E.] Med Univ South Carolina, Ctr Hlth Dispar Res, Dept Med, 135 Rutledge Ave,Room 280G, Charleston, SC 29425 USA. [Walker, Rebekah J.; Williams, Joni Strom; Egede, Leonard E.] Med Univ South Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC USA. [Walker, Rebekah J.; Williams, Joni Strom; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, HEROIC, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ South Carolina, Ctr Hlth Dispar Res, Dept Med, 135 Rutledge Ave,Room 280G, Charleston, SC 29425 USA. EM egedel@musc.edu FU HSRD VA [I50 HX001229]; NIDDK NIH HHS [K24 DK093699, R01 DK098529] NR 69 TC 2 Z9 2 U1 11 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD APR PY 2016 VL 351 IS 4 BP 366 EP 373 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DV1FJ UT WOS:000382665400007 PM 27079342 ER PT J AU Shearer, JE Jenkins, CH Magwood, GS Pope, CA AF Shearer, Jennifer E. Jenkins, Carolyn H. Magwood, Gayenell S. Pope, Charlene A. TI Contested Ownership of Disease and Ambulatory-Sensitive Emergency Department Visits for Type 2 Diabetes SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Type 2 diabetes; Emergency departmentuse; Ambulatory-sensitive conditions; Qualitative research; Grounded theory with dimensional analysis ID ILLNESS SELF-MANAGEMENT; AFRICAN-AMERICANS; GROUNDED THEORY; CARE; MODEL; PATIENT; LIFE AB Background: Approximately 21 million persons have diabetes and account for 11.9% of all emergency department (ED) visits for a total cost of $14.1 billion. Nonemergent visits for ambulatory-sensitive conditions that could be managed by the primary care provider make up almost one-third of the ED visits. African Americans comprise approximately 30% of South Carolina's population but make up approximately 50% of the ED visits for diabetes. The purpose of the research was to explore the experiences of 20 African-American adults with diabetes with ambulatory-sensitive ED use. Research Design and Methods: The research design for this study is grounded theory with dimensional analysis methods. Following ethics approval and informed consent, interviews were conducted, recorded and transcribed verbatim, and themes were analyzed to form the explanatory framework or matrix for ED use. The framework of context, conditions, processes and consequences provides a key for understanding the themes of the story embedded in the descriptive narratives. Results: The contested ownership of diabetes was the overarching perspective--"doing what I got to do," "it's always on mind wishing not to be a diabetic" and "it's a constant burden." And handling diabetes involved taking decisions "into your hands." The context of perceived urgency of symptoms included all the reasons that precipitated ED visit--personal experience, primary care access and services and social network support for decisions--influenced ownership of these decisions. C1 [Shearer, Jennifer E.; Jenkins, Carolyn H.] Charleston Southern Univ, Coll Nursing, Charleston, SC USA. [Jenkins, Carolyn H.; Magwood, Gayenell S.; Pope, Charlene A.] Med Univ South Carolina, Coll Nursing, 99 Jonathan Lucas St,MSC 160, Charleston, SC 29425 USA. [Pope, Charlene A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Jenkins, CH (reprint author), Med Univ South Carolina, Coll Nursing, 99 Jonathan Lucas St,MSC 160, Charleston, SC 29425 USA. EM Jenkins@musc.edu FU NINR NIH HHS [R15 NR009486] NR 35 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 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD APR PY 2016 VL 351 IS 4 BP 400 EP 406 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DV1FJ UT WOS:000382665400011 PM 27079346 ER PT J AU Santoro, N Braunstein, GD Butts, CL Martin, KA McDermott, M Pinkerton, JV AF Santoro, Nanette Braunstein, Glenn D. Butts, Cherie L. Martin, Kathryn A. McDermott, Michael Pinkerton, Joann V. TI Compounded Bioidentical Hormones in Endocrinology Practice: An Endocrine Society Scientific Statement SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CLINICAL-PRACTICE GUIDELINE; THYROXINE PLUS TRIIODOTHYRONINE; AMERICAN THYROID ASSOCIATION; PLACEBO-CONTROLLED TRIALS; QUALITY-OF-LIFE; FOLLICLE-STIMULATING-HORMONE; CARDIOVASCULAR RISK-FACTORS; METABOLIC-CLEARANCE RATE; SEXUAL DESIRE DISORDER AB Context: Custom-compounded bioidentical hormone therapy (HT) has become widely used in current endocrine practice, which has led to unnecessary risks with treatment. Objective: This scientific statement reviews the pharmacology and physiology of popular compounded hormones and the misconceptions associated with these therapies. The hormones reviewed include: estradiol and estrogens, progesterone and progestins, testosterone, dehydroepiandrosterone, levothyroxine, and triiodothyronine. Results: Overall, there is a general lack of standardization and quality control regarding how custom-compounded bioidentical hormones are produced and administered, leading to the possibility of overdosing, underdosing, or contamination. There is also recent evidence of patient harm and death associated with treatment, as seen with fungus-contaminated glucocorticoid preparations. With estrogen, progestin, and dehydroepiandrosterone treatments, the practice of baseline hormone measurements to replace "abnormal" hormone deficiencies has no basis in medical practice. Furthermore, there is no evidence that monitoring compounded HT with serial salivary or blood testing is effective, except in the case of thyroid hormone. Finally, no evidence supports the popularized notion that custom-compounded bioidentical hormones have fewer risks when compared with Food and Drug Administration (FDA)-approved hormone treatments. Conclusion: The widespread availability of FDA-approved bioidentical hormones produced in monitored facilities demonstrates a high quality of safety and efficacy in trials; therefore, there is no rationale for the routine prescribing of unregulated, untested, and potentially harmful custom-compounded bioidentical HTs. Clinicians are encouraged to prescribe FDA-approved hormone products according to labeling indications and to avoid custom-compounded hormones. C1 [Santoro, Nanette] Univ Colorado, Sch Med, Dept Obstet & Gynecol, Aurora, CO 80045 USA. [McDermott, Michael] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. [Braunstein, Glenn D.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Butts, Cherie L.] Biogen, Program Leadership, Cambridge, MA 02142 USA. [Martin, Kathryn A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pinkerton, Joann V.] Univ Virginia, Dept Obstet & Gynecol, Midlife Hlth, Charlottesville, VA 22908 USA. RP Santoro, N (reprint author), Univ Colorado, Sch Med, Mail Stop B-198,12631 East 17th Ave, Aurora, CO 80045 USA. EM nanette.santoro@ucdenver.edu FU Bayer, Inc; Pfizer; Noven Pharmaceuticals; Novo Nordisk; TherapeuticsMD; Shionogi; Endoceutics FX Disclosure Summary: N.S. received grant support from Bayer, Inc and stock options from Menogenix; G.D.B. worked on the editorial staff at Merck, participated in a mock Food and Drug Administration meeting with Amgen, and worked as a consultant at Allergan; C.L.B. was employed at Biogen; K.A.M. and M.M. has nothing to declare; and J.V.P. received consultant fees from Pfizer, Noven Pharmaceuticals, Novo Nordisk, TherapeuticsMD, and Shionogi (paid directly to the University of Virginia), and received research grants from TherapeuticsMD and Endoceutics (paid directly to the University of Virginia). NR 249 TC 2 Z9 2 U1 3 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2016 VL 101 IS 4 BP 1318 EP 1343 DI 10.1210/jc.2016-1271 PG 26 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DU0YP UT WOS:000381931400002 PM 27032319 ER PT J AU Yin, XY Subramanian, S Willinger, CM Chen, G Juhasz, P Courchesne, P Chen, BH Li, XH Hwang, SJ Fox, CS O'Donnell, CJ Muntendam, P Fuster, V Bobeldijk-Pastorova, I Sookoian, SC Pirola, CJ Gordon, N Adourian, A Larson, MG Levy, D AF Yin, Xiaoyan Subramanian, Subha Willinger, Christine M. Chen, George Juhasz, Peter Courchesne, Paul Chen, Brian H. Li, Xiaohang Hwang, Shih-Jen Fox, Caroline S. O'Donnell, Christopher J. Muntendam, Pieter Fuster, Valentin Bobeldijk-Pastorova, Ivana Sookoian, Silvia C. Pirola, Carlos J. Gordon, Neal Adourian, Aram Larson, Martin G. Levy, Daniel TI Metabolite Signatures of Metabolic Risk Factors and their Longitudinal Changes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-HEART-DISEASE; LYSOPHOSPHATIDIC ACID; CARDIOVASCULAR-DISEASE; ALANINE AMINOTRANSFERASE; INSULIN-RESISTANCE; LACTATE LEVELS; PLANT STEROLS; STUDY DESIGN; AMINO-ACID; AUTOTAXIN AB Context: Metabolic dysregulation underlies key metabolic risk factors-obesity, dyslipidemia, and dysglycemia. Objective: To uncover mechanistic links between metabolomic dysregulation and metabolic risk by testing metabolite associations with risk factors cross-sectionally and with risk factor changes over time. Design: Cross-sectional-discovery samples (n = 650; age, 36-69 years) from the Framingham Heart Study (FHS) and replication samples (n = 670; age, 61-76 years) from the BioImage Study, both following a factorial design sampled from high vs low strata of body mass index, lipids, and glucose. Longitudinal-FHS participants (n = 554) with 5-7 years of follow-up for risk factor changes. Setting: Observational studies. Participants: Cross-sectional samples with or without obesity, dysglycemia, and dyslipidemia, excluding prevalent cardiovascular disease and diabetes or dyslipidemia treatment. Age-and sex-matched by group. Interventions: None. Main Outcome Measure(s): Gas chromatography-mass spectrometry detected 119 plasma metabolites. Cross-sectional associations with obesity, dyslipidemia, and dysglycemia were tested in discovery, with external replication of 37 metabolites. Single-and multi-metabolite markers were tested for association with longitudinal changes in risk factors. Results: Cross-sectional metabolite associations were identified with obesity (n = 26), dyslipidemia (n = 21), and dysglycemia (n = 11) in discovery. Glutamic acid, lactic acid, and sitosterol associated with all three risk factors in meta-analysis (P < 4.5 x 10(-4)). Metabolites associated with longitudinal risk factor changes were enriched for bioactive lipids. Multi-metabolite panels explained 2.5-15.3% of longitudinal changes in metabolic traits. Conclusions: Cross-sectional results implicated dysregulated glutamate cycling and amino acid metabolism in metabolic risk. Certain bioactive lipids were associated with risk factors cross-sectionally and over time, suggesting their upstream role in risk factor progression. Functional studies are needed to validate findings and facilitate translation into treatments or preventive measures. C1 [Yin, Xiaoyan; Subramanian, Subha; Willinger, Christine M.; Chen, George; Courchesne, Paul; Chen, Brian H.; Hwang, Shih-Jen; Fox, Caroline S.; O'Donnell, Christopher J.; Larson, Martin G.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. [Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02118 USA. [Yin, Xiaoyan; Larson, Martin G.] Sch Publ Hlth, Boston, MA 02118 USA. [Subramanian, Subha; Willinger, Christine M.; Chen, George; Chen, Brian H.; Hwang, Shih-Jen; Fox, Caroline S.; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. [Juhasz, Peter; Li, Xiaohang; Muntendam, Pieter; Gordon, Neal; Adourian, Aram] BG Med Inc, 610 Lincoln St, Waltham, MA 02451 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Med Sch, Boston, MA 02115 USA. [O'Donnell, Christopher J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Fuster, Valentin] Mt Sinai Sch Med, New York, NY 10029 USA. [Fuster, Valentin] Ctr Nacl Invest Cardiovasc, Madrid 28029, Spain. [Bobeldijk-Pastorova, Ivana] TNO Triskel BV Inc, NL-3704 HE Zeist, Netherlands. [Sookoian, Silvia C.; Pirola, Carlos J.] Univ Buenos Aires, Inst Med Res A Lanari IDIM, Natl Sci & Tech Res Council, C11428, Buenos Aires, DF, Argentina. [Levy, Daniel] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Larson, MG; Levy, D (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.; Adourian, A (reprint author), BG Med Inc, 610 Lincoln St, Waltham, MA 02451 USA. EM aadourian@bg-medicine.com; mlarson@bu.edu; levyd@nih.gov RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 FU National Institutes of Health [N01-HC-25195]; Division of Intramural Research of the National Heart, Lung, and Blood Institute FX The Framingham Heart Study is funded by National Institutes of Health contract N01-HC-25195; this research was also supported by the Division of Intramural Research of the National Heart, Lung, and Blood Institute. This study was made possible by a cooperative research and development agreement between BG Medicine, Inc, Boston University, and the National Heart, Lung, and Blood Institute. NR 65 TC 0 Z9 0 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 APR PY 2016 VL 101 IS 4 BP 1779 EP 1789 DI 10.1210/jc.2015-2555 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DU0YP UT WOS:000381931400053 PM 26908103 ER PT J AU Larsen, BA Wassel, CL Kritchevsky, SB Strotmeyer, ES Criqui, MH Kanaya, AM Fried, LF Schwartz, AV Harris, TB Ix, JH AF Larsen, Britta A. Wassel, Christina L. Kritchevsky, Stephen B. Strotmeyer, Elsa S. Criqui, Michael H. Kanaya, Alka M. Fried, Linda F. Schwartz, Ann V. Harris, Tamara B. Ix, Joachim H. CA Hlth ABC Study TI Association of Muscle Mass, Area, and Strength With Incident Diabetes in Older Adults: The Health ABC Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SKELETAL-MUSCLE; INSULIN SENSITIVITY; GLUCOSE-TOLERANCE; BODY-COMPOSITION; ADIPOSE-TISSUE; WOMEN; RESISTANCE; MORTALITY; MEN; OVERWEIGHT AB Context: Skeletal muscle plays a key role in glucose regulation, yet the association between muscle quantity or quality and the risk of developing type 2 diabetes has not been explored. Objective: The objective of the study was to assess the association between muscle quantity and strength and incident diabetes and to explore whether this association differs by body mass index (BMI) category. Design and Setting: Participants were 2166 older adults in the Health, Aging, and Body Composition Study who were free of diabetes at baseline (1997-1998). Computed tomography and dual-energy x-ray absorptiometry were used to measure abdominal and thigh muscle area and total body lean mass, respectively. Strength was quantified by grip and knee extensions. Main Outcome Measure: Incident diabetes, defined as fasting glucose of 126 mg/dL or greater, a physician's diagnosis, and/or the use of hypoglycemic medication were measured. Results: After a median 11.3 years of follow-up, there were 265 incident diabetes cases (12.2%). In fully adjusted models, no association was found between muscle or strength measures and incident diabetes (for all, P > .05). For women, there was a significant interaction with BMI category for both abdominal and thigh muscle, such that greater muscle predicted lower risk of incident diabetes for normal-weight women(hazard ratio 0.37 [0.17-0.83] and 0.58 [0.27-1.27] per SD, respectively) and a greater risk for overweight and obese women(hazard ratio 1.23 [0.98-1.54] and 1.28 [1.00-1.64], respectively). No significant interactions by BMI category existed for strength measures or any measures for men (for all, P > .05). Conclusions: Greater muscle area is associated with a lower risk of incident diabetes for older normal-weight women but not for men or overweight women. C1 [Larsen, Britta A.; Criqui, Michael H.; Ix, Joachim H.] Univ Calif San Diego, Dept Family Med & Publ Hlth, 9500 Gilman Dr, San Diego, CA 92093 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA. [Wassel, Christina L.] Univ Vermont, Coll Med, Dept Pathol & Lab Med, Burlington, VT 05446 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27157 USA. [Kritchevsky, Stephen B.] Sch Med, Winston Salem, NC 27157 USA. [Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15219 USA. [Schwartz, Ann V.] Univ Calif San Francisco, Div Gen Internal Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Fried, Linda F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. RP Larsen, BA (reprint author), Univ Calif San Diego, Dept Family Med & Publ Hlth, 9500 Gilman Dr, San Diego, CA 92093 USA. EM blarsen@ucsd.edu FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research Grant [R01-NR012459]; Intramural Research Program of the National Institute on Aging; Career Development Grant from National Institute of Diabetes and Digestive and Kidney Diseases [K01 DK101650]; Established Investigator Award from American Heart Association [14EIA18560026] FX This work was supported Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 from the National Institute on Aging, National Institute on Aging Grant R01-AG028050 and National Institute of Nursing Research Grant R01-NR012459. This research was also supported in part by the Intramural Research Program of the National Institute on Aging. B.L. was supported by Career Development Grant K01 DK101650 from the National Institute of Diabetes and Digestive and Kidney Diseases. J.I. was supported by an Established Investigator Award from the American Heart Association (14EIA18560026). NR 26 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2016 VL 101 IS 4 BP 1847 EP 1855 DI 10.1210/jc.2015-3643 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DU0YP UT WOS:000381931400060 PM 26930180 ER PT J AU Babich, LP Charns, MP McIntosh, N Lerner, B Burgess, JF Stolzmann, KL Lukas, CV AF Babich, Lauren P. Charns, Martin P. McIntosh, Nathalie Lerner, Barbara Burgess, James F., Jr. Stolzmann, Kelly L. Lukas, Carol VanDeusen TI Building Systemwide Improvement Capability: Does an Organization's Strategy for Quality Improvement Matter? SO QUALITY MANAGEMENT IN HEALTH CARE LA English DT Article DE organizational change; performance improvement capability; quality improvement ID HEALTH-CARE; PERFORMANCE IMPROVEMENT; LEARNING ORGANIZATION; IMPLEMENTATION; MANAGEMENT; HOSPITALS; IMPACT; KEYS AB Objectives: Health care organizations have used different strategies to implement quality improvement (QI) programs but with only mixed success in implementing and spreading QI organization-wide. This suggests that certain organizational strategies may be more successful than others in developing an organization's improvement capability. To investigate this, our study examined how the primary focus of grant-funded QI efforts relates to (1) key measures of grant success and (2) organization-level measures of success in QI and organizational learning. Methods: Using a mixed-methods design, we conducted one-way analyses of variance to relate Veterans Affairs administrative survey data to data collected as part of a 3.5-year evaluation of 29 health care organization grant recipients. We then analyzed qualitative evidence from the evaluation to explain our results. Results: We found that hospitals that focused on developing organizational infrastructure to support QI implementation compared with those that focused on training or conducting projects rated highest (at alpha = .05) on all 4 evaluation measures of grant success and all 3 systemwide survey measures of QI and organizational learning success. Conclusions: This study adds to the literature on developing organizational improvement capability and has practical implications for health care leaders. Focusing on either projects or staff training in isolation has limited value. Organizations are more likely to achieve systemwide transformation of improvement capability if their strategy emphasizes developing or strengthening organizational systems, structures, or processes to support direct improvement efforts. C1 [Babich, Lauren P.; Charns, Martin P.; McIntosh, Nathalie; Lerner, Barbara; Burgess, James F., Jr.; Stolzmann, Kelly L.; Lukas, Carol VanDeusen] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 150 S Huntington Ave,Bldg 9, Boston, MA 02130 USA. [Babich, Lauren P.] Boston Univ, Dept Family Med, Boston, MA 02215 USA. [Charns, Martin P.; Burgess, James F., Jr.; Lukas, Carol VanDeusen] Boston Univ, Dept Hlth Law Policy & Management, Boston, MA 02215 USA. RP Babich, LP (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 150 S Huntington Ave,Bldg 9, Boston, MA 02130 USA. EM lbabich@bu.edu FU Veterans Affairs Office of Systems Redesign FX The authors have no conflicts of interest or disclaimers to report. The study team drew heavily from an evaluation funded by the Veterans Affairs Office of Systems Redesign. NR 27 TC 0 Z9 0 U1 6 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1063-8628 EI 1550-5154 J9 QUAL MANAG HEALTH CA JI Qual. Manag. Health Care PD APR-JUN PY 2016 VL 25 IS 2 BP 92 EP 101 DI 10.1097/QMH.0000000000000089 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DT4UQ UT WOS:000381477000004 PM 27031358 ER PT J AU Hara, T Jaffer, FA AF Hara, Tetsuya Jaffer, Farouc A. TI Intravascular NIRF Molecular Imaging Approaches in Coronary Artery Disease SO CURRENT CARDIOVASCULAR IMAGING REPORTS LA English DT Article DE Intravascular near-infrared fluorescence (NIRF); Intravascular imaging; Inflammation; Coronary artery disease (CAD) ID NEAR-INFRARED FLUORESCENCE; CONTRAST AGENT; IN-VIVO; ATHEROSCLEROSIS; THROMBUS; CATHETER; INFLAMMATION; ULTRASOUND; EP-2104R; OCT AB Progression of vulnerable coronary atherosclerotic plaques underlies most episodes of acute myocardial infarction and sudden cardiac death. Recent advances in biological/molecular imaging technology are now enabling the accurate identification of high-risk plaques and coronary stents in living subjects. Due to their smaller caliber and susceptibility to cardiorespiratory motion, noninvasive molecular imaging of human coronary arteries remains challenging. Therefore, intravascular high-resolution molecular imaging approaches appear necessary to resolve molecular features of human coronary arteries and stents. Here we present recent progress in intravascular near-infrared fluorescence (NIRF) molecular imaging, including the evolution from stand-alone NIRF systems to those integrated with structural imaging methods including optical coherence tomography and intravascular ultrasound. Preclinical demonstrations of imaging inflammation, fibrin, and endothelial impairment are highlighted. We then close with a discussion of translation of NIRF imaging to the cardiac catheterization laboratory and showcase first-in-human intracoronary imaging results of NIR autofluorescence in CAD. C1 [Hara, Tetsuya] Kobe Univ, Grad Sch Med, Div Cardiovasc Med, Chuo Ku, 7-5-1 Kusunoki Cho, Kobe, Hyogo, Japan. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu NR 28 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1941-9066 EI 1941-9074 J9 CURR CARDIOVASC IMAG JI CURR. CARDIOVASC. IMAGING REP. PD APR PY 2016 VL 9 IS 4 AR UNSP 13 DI 10.1007/s12410-016-9374-0 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DU5KD UT WOS:000382249700002 ER PT J AU Hjelmeland, A Zhang, JH AF Hjelmeland, Anita Zhang, Jianhua TI Metabolic, autophagic, and mitophagic activities in cancer initiation and progression SO BIOMEDICAL JOURNAL LA English DT Review DE Autophagy; Cancer; Mitochondria; Mitophagy; Oxidative stress; Reactive species ID TUMOR-SUPPRESSOR GENE; POSITRON-EMISSION-TOMOGRAPHY; FACTOR-INDEPENDENT SURVIVAL; TRANSCRIPTION FACTOR NRF2; PYRUVATE-KINASE M2; NITRIC-OXIDE; REACTIVE OXYGEN; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; THERAPEUTIC TARGET AB Cancer is a complex disease marked by uncontrolled cell growth and invasion. These processes are driven by the accumulation of genetic and epigenetic alterations that promote cancer initiation and progression. Contributing to genome changes are the regulation of oxidative stress and reactive species-induced damage to molecules and organelles. Redox regulation, metabolic plasticity, autophagy, and mitophagy play important and interactive roles in cancer hallmarks including sustained proliferation, activated invasion, and replicative immortality. However, the impact of these processes can differ depending on the signaling pathways altered in cancer, tumor type, tumor stage, and/or the differentiation state. Here, we highlight some of the representative studies on the impact of oxidative and nitrosative activities, mitochondrial bioenergetics, metabolism, and autophagy and mitophagy in the context of tumorigenesis. We discuss the implications of these processes for cellular activities in cancer for anti-cancer-based therapeutics. C1 [Hjelmeland, Anita] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA. [Hjelmeland, Anita; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL USA. [Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Biomed Res Bldg 2,901 19th St South, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Biomed Res Bldg 2,901 19th St South, Birmingham, AL 35294 USA. EM zhanja@uab.edu NR 168 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2319-4170 EI 2320-2890 J9 BIOMED J JI Biomed. J. PD APR PY 2016 VL 39 IS 2 BP 98 EP 106 DI 10.1016/j.bj.2015.10.002 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DS3VN UT WOS:000380710900003 PM 27372165 ER PT J AU Anahtar, MN Bowman, BA Kwon, DS AF Anahtar, Melis N. Bowman, Brittany A. Kwon, Douglas S. TI Efficient Nucleic Acid Extraction and 16S rRNA Gene Sequencing for Bacterial Community Characterization SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Molecular Biology; Issue 110; Microbiome; metagenomics; 16S; DNA extraction; RNA extraction; bacteria; human sequencing; next-generation sequencing; high-throughput sequencing; vaginal; stool; swab ID MICROBIOME; DIVERSITY AB There is a growing appreciation for the role of microbial communities as critical modulators of human health and disease. High throughput sequencing technologies have allowed for the rapid and efficient characterization of bacterial communities using 16S rRNA gene sequencing from a variety of sources. Although readily available tools for 16S rRNA sequence analysis have standardized computational workflows, sample processing for DNA extraction remains a continued source of variability across studies. Here we describe an efficient, robust, and cost effective method for extracting nucleic acid from swabs. We also delineate downstream methods for 16S rRNA gene sequencing, including generation of sequencing libraries, data quality control, and sequence analysis. The workflow can accommodate multiple samples types, including stool and swabs collected from a variety of anatomical locations and host species. Additionally, recovered DNA and RNA can be separated and used for other applications, including whole genome sequencing or RNA-seq. The method described allows for a common processing approach for multiple sample types and accommodates downstream analysis of genomic, metagenomic and transcriptional information. C1 [Anahtar, Melis N.; Bowman, Brittany A.; Kwon, Douglas S.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. RP Kwon, DS (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. EM dkwon@mgh.harvard.edu FU Bill and Melinda Gates Foundation; NIAID [1R01AI111918]; Burroughs Wellcome Fund; NIGMS [T32GM007753]; Paul and Daisy Soros Fellowship FX We would like to thank Elizabeth Byrne, David Gootenberg, and Christina Gosmann for critical feedback on the protocol; Megan Baldridge, Scott Handley, Cindy Monaco, and Jason Norman for sample preparation guidance and demonstrations; Wendy Garrett, Curtis Huttenhower, Skip Virgin, and Bruce Walker for protocol advice and fruitful discussions; and Jessica Hoisington-Lopez for sequencing support. This work was supported by the Bill and Melinda Gates Foundation and the NIAID (1R01AI111918). D.S.K. received additional support from the Burroughs Wellcome Fund. M.N.A. was supported by award number T32GM007753 from the NIGMS, and the Paul and Daisy Soros Fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIGMS or the NIH. NR 26 TC 0 Z9 0 U1 6 U2 6 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD APR PY 2016 IS 110 AR e53939 DI 10.3791/53939 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DR9ZX UT WOS:000380256000067 ER PT J AU Alidina, S Rosenthal, M Schneider, E Singer, S AF Alidina, Shehnaz Rosenthal, Meredith Schneider, Eric Singer, Sara TI Coordination within medical neighborhoods: Insights from the early experiences of Colorado patient-centered medical homes SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE coordination mechanisms; medical neighborhoods; patient-centered medical homes ID PRIMARY-CARE; ORGANIZATION DESIGN; INPUT UNCERTAINTY; MECHANISMS; PHYSICIAN; NETWORKS; FORMS; VIEW AB Background: The term "medical neighborhood" refers to relationships that patient-centered medical homes (PCMHs) seek to establish with other providers to facilitate coordinated patient care. Yet, how PCMHs can accomplish this coordination is not well understood. Purpose: Drawing upon organizational theory (Galbraith, 1974; Mintzberg, 1980; Thompson, 1967), we explored how PCMHs use coordination mechanisms to build and optimize their medical neighborhoods. Methodology: We used mixed methods, blending data collected via interviews and surveys with practice leaders and care coordinators at 30 months after a PCMH collaborative intervention in Colorado as well as surveys from all providers from 13 PCMHs before and 30 months after the intervention. We used thematic analysis to understand the role and use of coordination mechanisms by PCMHs and changes in the ability to coordinate and deliver care continuity. Findings: PCMHs drew on four coordination mechanisms to build relationships with their medical neighbors: interorganizational routines to improve reliability of information flow; information connectivity to facilitate continuity and safe care; boundary spanners to integrate care across silos; and communication, negotiation, and decision mechanisms to introduce shared accountability. When providers were fairly confident of the patient's diagnosis and management required sequential interactions (such as tests or procedures), PCMHs tended to coordinate care through interorganizational routines and information connectivity. When a diagnosis was less certain and required reciprocal interaction (i.e., consultation), PCMHs employed boundary spanners and communication, negotiation, and decision mechanisms. Practice Implications: Use of coordination mechanisms by PCMHs can help to improve care coordination in medical neighborhoods. All four mechanisms appear to be useful. The optimal mix of coordination mechanisms requires attention to patient context. Successfully building medical neighborhoods also requires meta-leaders, collaboration competencies, and high-quality relationships between providers in primary care, specialty care, and hospitals. C1 [Alidina, Shehnaz] Brigham & Womens Hosp, Ariadne Labs, 75 Francis St, Boston, MA 02115 USA. [Alidina, Shehnaz] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Rosenthal, Meredith] Harvard TH Chan Sch Publ Hlth, Hlth Econ & Policy, Boston, MA USA. [Rosenthal, Meredith] Harvard TH Chan Sch Publ Hlth, Divers, Boston, MA USA. [Schneider, Eric] RAND Boston, Boston, MA USA. [Schneider, Eric] Harvard Med Sch, Harvard TH Chan Sch Publ Hlth, Brigham Womens Hosp, Boston, MA 02115 USA. [Singer, Sara] Harvard Med Sch, Harvard TH Chan Sch Publ Hlth, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Alidina, S (reprint author), Brigham & Womens Hosp, Ariadne Labs, 75 Francis St, Boston, MA 02115 USA.; Alidina, S (reprint author), Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA. EM shehnaz.alidina@mail.harvard.edu OI Schneider, Eric/0000-0002-1132-5084 FU Commonwealth Fund; Colorado Trust; Canada Program; Weatherhead Center for International Affairs; Canadian Federation of University Women FX The authors gratefully acknowledge the individuals who gave so generously of their time for interviews. We would also like to acknowledge the assistance of Dr. Scott Hammond, Dr. David Ehrenberger, and Caitlin Barba for their valuable input on the development of the medical neighborhoods survey and Josie Fisher for verifying the qualitative coding. The research was approved by the institutional review board at the Harvard School of Public Health. The effort of Meredith Rosenthal, Eric Schneider, and Sara Singer was supported by the Commonwealth Fund and Colorado Trust. S. Alidina's effort on this project was supported by dissertation grants from the Canada Program, the Weatherhead Center for International Affairs, and the Canadian Federation of University Women. NR 44 TC 1 Z9 1 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0361-6274 EI 1550-5030 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD APR-JUN PY 2016 VL 41 IS 2 BP 101 EP 112 DI 10.1097/HMR.0000000000000063 PG 12 WC Health Policy & Services SC Health Care Sciences & Services GA DR7WE UT WOS:000380109600003 PM 26259020 ER PT J AU Miloslavsky, EM Boyer, D Winn, AS Stafford, DEJ McSparron, JI AF Miloslavsky, Eli M. Boyer, Debra Winn, Ariel S. Stafford, Diane E. J. McSparron, Jakob I. TI Fellows as Teachers: Raising the Educational Bar SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB Fellows are expected to educate trainees, peers, and patients, during and long after fellowship. However, there has been relatively little emphasis on the acquisition of teaching skills in fellowship programs. Challenges to teaching by fellows during subspecialty training include demanding clinical duties, their limited knowledge base in the field, brief contact time with learners during consultative roles, and, for new fellows, personal unfamiliarity with the learners and hospital culture. Fellows' teaching skills can be improved by formal curricula addressing teaching, and by direct observation and feedback of teaching akin to what is provided for learning clinical care. Further expansion of fellow-as-teacher programs will allow in-depth training for fellows seeking careers as medical educators. Even without such dedicated programs, emphasis on honing teaching skills during fellowship will telegraph the importance of teaching and help evolve divisional culture. Such efforts can have a positive impact on patients and learners, and enhance the teaching skills of future faculty. C1 [Miloslavsky, Eli M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Boyer, Debra] Harvard Med Sch, Boston Childrens Hosp, Div Resp Dis, Boston, MA USA. [Winn, Ariel S.] Harvard Med Sch, Boston Childrens Hosp, Div Gen Pediat, Boston, MA USA. [Stafford, Diane E. J.] Harvard Med Sch, Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [McSparron, Jakob I.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, Boston, MA USA. [McSparron, Jakob I.] Beth Israel Deaconess Med Ctr, Carl J Shapiro Inst Educ & Res, Boston, MA USA. RP McSparron, JI (reprint author), 330 Brookline Ave,KSB 23, Boston, MA 02215 USA. EM jmcsparr@bidmc.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD APR PY 2016 VL 13 IS 4 BP 465 EP 468 DI 10.1513/AnnalsATS.201601-026PS PG 4 WC Respiratory System SC Respiratory System GA DR6BT UT WOS:000379986900006 PM 26835749 ER PT J AU Russell, DW Gaggar, A Solomon, GM AF Russell, Derek W. Gaggar, Amit Solomon, George M. TI Neutrophil Fates in Bronchiectasis and Alpha-1 Antitrypsin Deficiency SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB The neutrophil is a powerful cellular defender of the vulnerable interface between the environment and pulmonary tissues. This cell's potent weapons are carefully calibrated in the healthy state to maximize effectiveness in fighting pathogens while minimizing tissue damage and allowing for repair of what damage does occur. The three related chronic airway disorders of cystic fibrosis, non-cystic fibrosis bronchiectasis, and alpha-1 antitrypsin deficiency all demonstrate significant derangements of this homeostatic system that result in their respective pathologies. An important shared feature among them is the inefficient resolution of chronic inflammation that serves as a central means for neutrophil-driven lung damage resulting in disease progression. Examining the commonalities and divergences between these diseases in the light of their immunopathology is informative and may help guide us toward future therapeutics designed to modulate the neutrophil's interplay with the pulmonary environment. C1 [Russell, Derek W.; Gaggar, Amit; Solomon, George M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Gaggar, Amit; Solomon, George M.] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL USA. [Russell, Derek W.; Gaggar, Amit] Univ Alabama Birmingham, Program Protease & Matrix Biol, Birmingham, AL USA. [Gaggar, Amit] Birmingham Vet Affairs Med Ctr, Med Serv, Birmingham, AL USA. RP Solomon, GM (reprint author), 1900 Univ Blvd,THT 422, Birmingham, AL 35294 USA. EM msolomon@uab.edu FU NIH [HL102371, HL126596]; Veterans Administration [1 I01 BX001756]; Cystic Fibrosis Foundation [CLANCY09Y0, SORSCH15RO] FX Supported by the NIH (HL102371 and HL126596 to A.G.), the Veterans Administration (1 I01 BX001756 to A.G.), and the Cystic Fibrosis Foundation (CLANCY09Y0 and SORSCH15RO to G.M.S.). NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD APR PY 2016 VL 13 SU 2 BP S123 EP S129 DI 10.1513/AnnalsATS.201512-805KV PG 7 WC Respiratory System SC Respiratory System GA DR7QM UT WOS:000380094800005 PM 27115946 ER PT J AU Slovis, BH Shah, KH Yeh, DD Seethala, R Kaafarani, HMA Eikermann, M Raja, AS Lee, J AF Slovis, Benjamin H. Shah, Kaushal H. Yeh, D. Dante Seethala, Raghu Kaafarani, Haytham M. A. Eikermann, Matthias Raja, Ali S. Lee, Jarone TI Significant but reasonable radiation exposure from computed tomography-related medical imaging in the ICU SO EMERGENCY RADIOLOGY LA English DT Article DE Computed tomography (CT); Radiation exposure; Cancer; Lifetime attributable risk ID CANCER-RISKS; CT; TRENDS; SCANS AB Admission to an intensive care unit (ICU) is associated with increased medical imaging and radiation exposure, yet few studies have estimated the risk of cancer associated with these examinations. The purpose of this study was to review computed tomography (CT) scans performed on patients admitted to two urban academic ICUs, predict their radiation exposure, and calculate their estimated lifetime attributable risk of cancer (LAR). An electronic chart review was performed on all CT scans performed between January 2007 and December 2011. The estimated effective dose of radiation was calculated for each CT, and the LAR for each patient was predicted. Mean radiation exposure was 22.2 +/- 25.0 mSv with a mean LAR of 0.1 +/- 0.2 % and a median of 0.6 % with a range of < 0.001 to 3.4 %. Our cohort received radiation doses higher than recommended by guidelines; however, the critical nature of their admission may have warranted these imaging studies. Estimated risk of cancer in this population was overall low. C1 [Slovis, Benjamin H.; Shah, Kaushal H.] Icahn Sch Med Mt Sinai, Mt Sinai Hosp, Dept Emergency Med, New York, NY 10029 USA. [Yeh, D. Dante; Kaafarani, Haytham M. A.] Harvard Med Sch, Massachusetts Gen Hosp, Div Trauma Emergency Surg Surg Crit Care, Boston, MA USA. [Seethala, Raghu] Harvard Med Sch, Brigham & Womens Hosp, Dept Emergency Med, Boston, MA USA. [Eikermann, Matthias] Harvard Med Sch, Massachusetts Gen Hosp, Div Anesthesia Crit Care & Pain Med, Boston, MA USA. [Raja, Ali S.; Lee, Jarone] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lee, Jarone] 165 Cambridge St,Suite 810, Boston, MA 02114 USA. RP Lee, J (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA.; Lee, J (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM Benjamin.Slovis@mountsinai.org; Kaushal.Shah@mountsinai.org; dyeh2@mgh.harvard.edu; rseethala@partners.org; hkaafarani@mgh.harvard.edu; meikermann@partners.org; asraja@partners.org; lee.jarone@mgh.harvard.edu NR 25 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1070-3004 EI 1438-1435 J9 EMERG RADIOL JI Emerg. Radiol. PD APR PY 2016 VL 23 IS 2 BP 141 EP 146 DI 10.1007/s10140-015-1373-y PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DR1BI UT WOS:000379640600007 PM 26738733 ER PT J AU Bunch, PM Sheehan, SE Dyer, GS Sodickson, A Khurana, B AF Bunch, Paul M. Sheehan, Scott E. Dyer, George S. Sodickson, Aaron Khurana, Bharti TI A biomechanical approach to distal radius fractures for the emergency radiologist SO EMERGENCY RADIOLOGY LA English DT Review DE Radius; Fracture; Trauma; Wrist; Biomechanical; Mechanism ID TRIANGULAR FIBROCARTILAGE COMPLEX; RADIOULNAR JOINT SUBLUXATION; COMPUTED-TOMOGRAPHY; RADIOGRAPHIC EVALUATION; INTRAOBSERVER REPRODUCIBILITY; INTEROBSERVER RELIABILITY; INTRAARTICULAR FRACTURES; INTERNAL-FIXATION; EXTERNAL FIXATION; COLLES FRACTURES AB Distal radius fractures are the most common upper extremity fracture and account for approximately one sixth of all fractures treated in US emergency departments. These fractures are associated with significant morbidity and have a major economic impact. Radiographic evaluation of distal radius fractures is frequently performed in the emergency department setting, has a profound impact on initial management, and is essential to assessing the quality and relative success of the initial reduction. While the most appropriate definitive management of distal radius fractures remains controversial, overarching treatment principles reflect distal radius injury mechanisms and biomechanics. An intuitive understanding of the biomechanics of the distal radius and of common mechanisms of injury informs and improves the emergency radiologist's ability to identify key imaging findings with important management implications and to communicate the critical information that emergency physicians and orthopedic surgeons need to best manage distal radius fractures. C1 [Bunch, Paul M.; Sodickson, Aaron; Khurana, Bharti] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Sheehan, Scott E.] William S Middleton Mem Vet Adm Med Ctr, Dept Radiol, 2500 Overlook Terrace, Madison, WI 53705 USA. [Dyer, George S.] Harvard Med Sch, Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. RP Bunch, PM (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM paul.m.bunch@gmail.com NR 73 TC 2 Z9 2 U1 3 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1070-3004 EI 1438-1435 J9 EMERG RADIOL JI Emerg. Radiol. PD APR PY 2016 VL 23 IS 2 BP 175 EP 185 DI 10.1007/s10140-015-1363-0 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DR1BI UT WOS:000379640600012 PM 26564022 ER PT J AU Martin, PS Li, SL Nikiforow, S Alyea, EP Antin, JH Armand, P Cutler, CS Ho, VT Kekre, N Koreth, J Luckey, J Ritz, J Soiffer, RJ AF Martin, Paul S. Li, Shuli Nikiforow, Sarah Alyea, Edwin P., III Antin, Joseph H. Armand, Philippe Cutler, Corey S. Ho, Vincent T. Kekre, Natasha Koreth, John Luckey, John Ritz, Jerome Soiffer, Robert J. TI Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34(+) cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation SO HAEMATOLOGICA LA English DT Article ID VERSUS-HOST-DISEASE; IDENTICAL SIBLING TRANSPLANTATION; ACUTE MYELOCYTIC-LEUKEMIA; BONE-MARROW; STEM-CELLS; SURVIVAL; ENGRAFTMENT; RECIPIENTS; CHIMERISM; REMISSION AB Mobilized peripheral blood is the most common graft source for allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning. In assessing the effect of donor cell dose and graft composition on major transplant outcomes in the reduced-intensity setting, prior studies focused primarily on CD34(+) cell dose and reported conflicting results, especially in relation to survival end-points. While the impact of total nucleated cell dose has been less frequently evaluated, available studies suggest higher total nucleated cell dose is associated with improved survival outcomes in the reduced-intensity setting. In order to further explore the relationship between CD34(+) cell dose and total nucleated cell dose on reduced-intensity transplant outcomes, we analyzed the effect of donor graft dose and composition on outcomes of 705 patients with hematologic malignancies who underwent reduced-intensity peripheral blood stem cell transplantation at the Dana Farber Cancer Institute from 2000 to 2010. By multivariable analysis we found that higher total nucleated cell dose (top quartile; >= 10.8 x 10(10) cells) was associated with improved overall survival [HR 0.69 (0.54-0.88), P=0.0028] and progression-free survival [HR 0.68 (0.54-0.85), P=0.0006]. Higher total nucleated cell dose was independently associated with decreased relapse [HR 0.66 (0.51-0.85), P=0.0012] and increased incidence of chronic graft-versus-host disease [HR 1.4 (1.12-1.77), P=0.0032]. In contrast, higher doses of CD34(+) cells (top quartile; >= 10.9 x 10(6)/kg) had no significant effect on graft-versus-host disease or survival outcomes. These data suggest total nucleated cell dose is a more relevant prognostic variable for reduced-intensity transplant outcomes than the more commonly studied CD34(+) cell dose. C1 [Nikiforow, Sarah; Alyea, Edwin P., III; Antin, Joseph H.; Armand, Philippe; Cutler, Corey S.; Ho, Vincent T.; Kekre, Natasha; Koreth, John; Ritz, Jerome; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. [Nikiforow, Sarah; Alyea, Edwin P., III; Antin, Joseph H.; Armand, Philippe; Cutler, Corey S.; Ho, Vincent T.; Kekre, Natasha; Koreth, John; Ritz, Jerome; Soiffer, Robert J.] Harvard Med Sch, Boston, MA USA. [Li, Shuli] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Martin, Paul S.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Martin, Paul S.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Luckey, John] Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. RP Martin, PS (reprint author), Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.; Martin, PS (reprint author), Univ Washington, Sch Med, Seattle, WA 98195 USA. EM psmartin@fhcrc.org FU Ted and Eileen Pasquarello Research Fund at DFCI; National Institutes of Health (National Cancer Institute grant) [5R01-CA183559] FX The authors would like to thank the Ted and Eileen Pasquarello Research Fund at DFCI and the National Institutes of Health (National Cancer Institute grant 5R01-CA183559) for their support of this work. NR 24 TC 5 Z9 5 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD APR PY 2016 VL 101 IS 4 BP 499 EP 505 DI 10.3324/haematol.2015.134841 PG 7 WC Hematology SC Hematology GA DQ7NA UT WOS:000379393100025 PM 26768686 ER PT J AU Marx, BP Bovin, MJ Szafranski, DD Engel-Rebitzer, E Gallagher, MW Holowka, DW Schnurr, PP Rosen, RC Keane, TM AF Marx, Brian P. Bovin, Michelle J. Szafranski, Derek D. Engel-Rebitzer, Eden Gallagher, Matthew W. Holowka, Darren W. Schnurr, Paula P. Rosen, Raymond C. Keane, Terence M. TI Validity of Posttraumatic Stress Disorder Service Connection Status in Veterans Affairs Electronic Records of Iraq and Afghanistan Veterans SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID US VETERANS; PTSD; DISABILITY AB Objective: This study examined the extent to which veterans' posttraumatic stress disorder (PTSD) service connection (SC) status corresponded to their PTSD diagnostic status, as determined by a semistructured diagnostic interview. Method: Participants were 834 veterans in the Veterans After-Discharge Longitudinal Registry (Project VALOR), an observational registry of veterans with and without PTSD who are enrolled in the Veterans Affairs (VA) health care system. PTSD diagnostic status was confirmed using the Structured Clinical Interview for DSM-IV (SCID). Results: Concordance between PTSD SC status and current and lifetime PTSD diagnosis was 70.2% and 77.2%, respectively. Individuals with PTSD SC were twice as likely as those without PTSD SC to have a current SCID PTSD diagnosis (OR = 2.11 [95% CI, 1.47-3.04]; P<.001) and almost 3 times as likely to have a lifetime SCID PTSD diagnosis (OR = 2.72 [95% CI, 1.67-4.41]; P<.001). For current PTSD, results showed a slightly higher proportion of false positives-individuals who did not meet SCID criteria but who did have SC for PTSD-than false negatives-individuals who met SCID criteria but did not have SC for PTSD. For lifetime PTSD, the proportion of false negatives was approximately twice the proportion of false positives. Conclusions: PTSD diagnostic and SC status are discordant for a significant minority of veterans. Findings revealed that both the number of veterans who are service connected without meeting criteria for PTSD and the number of veterans who meet PTSD criteria but have not been granted SC status are concerning. (C) Copyright 2016 Physicians Postgraduate Press, Inc. C1 [Marx, Brian P.; Bovin, Michelle J.; Szafranski, Derek D.; Engel-Rebitzer, Eden; Gallagher, Matthew W.; Holowka, Darren W.; Keane, Terence M.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA USA. [Marx, Brian P.; Bovin, Michelle J.; Gallagher, Matthew W.; Holowka, Darren W.; Keane, Terence M.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Szafranski, Derek D.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Holowka, Darren W.] Rhode Isl Hosp, Providence, RI USA. [Schnurr, Paula P.] VA Med Ctr, VA Natl Ctr PTSD, White River Jct, VT USA. [Schnurr, Paula P.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Rosen, Raymond C.] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-4,150 South Huntington Ave, Boston, MA 02130 USA. EM brian.marx@va.gov FU US Department of Defense [W81XWH-08-2-0100, W81XWH-08-2-0102] FX This work was funded by US Department of Defense Awards W81XWH-08-2-0100 and W81XWH-08-2-0102. NR 20 TC 0 Z9 0 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2016 VL 77 IS 4 BP 517 EP 522 DI 10.4088/JCP.14m09666 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DQ5LU UT WOS:000379247700018 PM 26797388 ER PT J AU Gill, CM Torriani, M Murphy, R Harris, TB Miller, KK Klibanski, A Bredella, MA AF Gill, Corey M. Torriani, Martin Murphy, Rachel Harris, Tamara B. Miller, Karen K. Klibanski, Anne Bredella, Miriam A. TI Fat Attenuation at CT in Anorexia Nervosa SO RADIOLOGY LA English DT Article ID SUBCUTANEOUS ADIPOSE-TISSUE; COMPUTED-TOMOGRAPHY; PREMENOPAUSAL WOMEN; ABDOMINAL FAT; CANCER CACHEXIA; FEMALE-PATIENTS; WEIGHT-LOSS; RISK-FACTOR; BODY-FAT; OBESITY AB Purpose: To investigate the composition, cross-sectional area (CSA), and hormonal correlates of different fat depots in women with anorexia nervosa (AN) and control subjects with normal weights to find out whether patients with AN have lower fat CSA but higher attenuation than did control subjects and whether these changes may be mediated by gonadal steroids, cortisol, and thyroid hormones. Materials and Methods: This study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. Forty premenopausal women with AN and 40 normal-weight women of comparable age (mean age 6 standard deviation, 26 years 6 5) were studied. All individuals underwent computed tomography of the abdomen and thigh with a calibration phantom. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), thigh SAT, and thigh intermuscular adipose tissue CSA and attenuation were quantified. Serum estradiol, thyroid hormones, and urinary free cortisol levels were assessed. Variables were compared by using analysis of variance. Associations were examined by using linear regression analysis. Results: Women with AN had higher fat attenuation than did control subjects (-100.1 to -46.7 HU vs -117.6 to -61.8 HU, P < .0001), despite lower fat CSA (2.0-62.8 cm(2) vs 5.5-185.9 cm(2), P < .0001). VAT attenuation but not CSA was inversely associated with lowest prior lifetime body mass index in AN (r = -0.71, P = .006). Serum estradiol levels were inversely associated with fat attenuation (r = -0.34 to -0.61, P = .03 to <.0001) and were positively associated with fat CSA of all compartments (r = 0.42-0.64, P = .007 to <.0001). Thyroxine levels and urinary free cortisol levels were positively associated with thigh SAT attenuation (r = 0.64 [P = .006] and r = 0.68 [P = .0004], respectively) and were inversely associated with abdominal SAT and VAT CSA (r = 20.44 to 20.58, P = .04 to .02). Conclusion: Women with AN have differences in fat composition, with higher fat attenuation than that of control subjects, as well as low fat mass. VAT attenuation but not CSA is inversely associated with lowest prior lifetime body mass index, suggesting that fat attenuation may serve as a biomarker of prior and current disease status in AN. (C) RSNA, 2015 C1 [Gill, Corey M.; Torriani, Martin; Bredella, Miriam A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. [Miller, Karen K.; Klibanski, Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. [Murphy, Rachel; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. RP Bredella, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM mbredella@mgh.harvard.edu FU National Institutes of Health [R01 MH083657, R01 DK052625, R03 DK59297, M01 RR01066, UL1 RR025758, T32 DK 007028, K23 RR-23090] FX This research was supported by the National Institutes of Health (grants R01 MH083657, R01 DK052625, R03 DK59297, M01 RR01066, UL1 RR025758, T32 DK 007028, and K23 RR-23090). NR 27 TC 0 Z9 0 U1 3 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2016 VL 279 IS 1 BP 151 EP 157 DI 10.1148/radiol.2015151104 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP7WK UT WOS:000378709700014 PM 26509295 ER PT J AU Herold, CJ Lewin, JS Wibmer, AG Thrall, JH Krestin, GP Dixon, AK Schoenberg, SO Geckle, RJ Muellner, A Hricak, H AF Herold, Christian J. Lewin, Jonathan S. Wibmer, Andreas G. Thrall, James H. Krestin, Gabriel P. Dixon, Adrian K. Schoenberg, Stefan O. Geckle, Rena J. Muellner, Ada Hricak, Hedvig TI Imaging in the Age of Precision Medicine: Summary of the Proceedings of the 10th Biannual Symposium of the International Society for Strategic Studies in Radiology SO RADIOLOGY LA English DT Article ID ALZHEIMERS-DISEASE; DRUG DEVELOPMENT; COMPUTED-TOMOGRAPHY; UNITED-STATES; HEALTH-CARE; CANCER; QUALITY; LIVER; IMPROVEMENT; BIOMARKERS AB During the past decade, with its breakthroughs in systems biology, precision medicine (PM) has emerged as a novel health-care paradigm. Challenging reductionism and broad-based approaches in medicine, PM is an approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. It involves integrating information from multiple sources in a holistic manner to achieve a definitive diagnosis, focused treatment, and adequate response assessment. Biomedical imaging and imaging-guided interventions, which provide multiparametric morphologic and functional information and enable focused, minimally invasive treatments, are key elements in the infrastructure needed for PM. The emerging discipline of radiogenomics, which links genotypic information to phenotypic disease manifestations at imaging, should also greatly contribute to patient-tailored care. Because of the growing volume and complexity of imaging data, decision-support algorithms will be required to help physicians apply the most essential patient data for optimal management. These innovations will challenge traditional concepts of health care and business models. Reimbursement policies and quality assurance measures will have to be reconsidered and adapted. In their 10th biannual symposium, which was held in August 2013, the members of the International Society for Strategic Studies in Radiology discussed the opportunities and challenges arising for the imaging community with the transition to PM. This article summarizes the discussions and central messages of the symposium. (C) RSNA, 2015 C1 [Herold, Christian J.; Wibmer, Andreas G.] Med Univ Vienna, Dept Biomed Imaging & Imageguided Therapy, Vienna, Austria. [Lewin, Jonathan S.; Geckle, Rena J.] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Baltimore, MD USA. [Thrall, James H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Krestin, Gabriel P.] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Dixon, Adrian K.] Univ Cambridge, Dept Radiol, Cambridge, England. [Schoenberg, Stefan O.] Heidelberg Univ, Med Fac Mannheim, Univ Med Ctr Mannheim, Dept Clin Radiol & Nucl Med, Mannheim, Germany. [Muellner, Ada; Hricak, Hedvig] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave,Room C-278, New York, NY 10065 USA. RP Herold, CJ (reprint author), Med Univ Vienna, Dept Biomed Imaging & Imageguided Therapy, Vienna, Austria. NR 73 TC 5 Z9 7 U1 4 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2016 VL 279 IS 1 BP 226 EP 238 DI 10.1148/radiol.2015150709 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP7WK UT WOS:000378709700022 PM 26465058 ER PT J AU Hageman, MGJS Bossen, JK Neuhaus, V Mudgal, CS Ring, D AF Hageman, Michiel G. J. S. Bossen, Jeroen K. Neuhaus, Valentin Mudgal, Chaitanya S. Ring, David CA Sci Variation Grp TI Assessment of Decisional Conflict about the Treatment of Carpal Tunnel Syndrome, Comparing Patients and Physicians SO ARCHIVES OF BONE AND JOINT SURGERY-ABJS LA English DT Article DE Carpal Tunnel Syndrome; Decision aids; Hand surgery; Shared decision makin ID RANDOMIZED-TRIAL; BREAST-CANCER; SURGERY; QUESTIONNAIRE; CARE; PAIN; AID AB Background: As part of the process of developing a decision aid for carpal tunnel syndrome (CTS) according to the Ottawa Decision Support Framework, we were interested in the level of 'decisional conflict' of hand surgeons and patients with CTS. This study addresses the null hypothesis that there is no difference between surgeon and patient decisional conflict with respect to test and treatment options for CTS. Secondary analyses assess the impact of patient and physician demographics and the strength of the patient-physician relationship on decisional conflict. Methods: One-hundred-twenty-three observers of the Science of Variation Group (SOVG) and 84 patients with carpal tunnel syndrome completed a survey regarding the Decisional Conflict Scale. Patients also filled out the Pain Self-efficacy Questionnaire (PSEQ) and the Patient Doctor Relationship Questionnaire (PDRQ-9). Results: On average, patients had significantly greater decision conflict and scored higher on most subscales of the decisional conflict scale than hand surgeons. Factors associated with greater decision conflict were specific hand surgeon, less self-efficacy (confidence that one can achieve one's goals in spite of pain), and higher PDRQ (relationship between patient and doctor). Surgeons from Europe have-on average-significantly more decision conflict than surgeons in the United States of America. Conclusions: Patients with CTS have more decision conflict than hand surgeons. Decision aids might help narrow this gap in decisional conflict. C1 [Hageman, Michiel G. J. S.; Bossen, Jeroen K.; Neuhaus, Valentin; Mudgal, Chaitanya S.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. [Hageman, Michiel G. J. S.; Bossen, Jeroen K.; Neuhaus, Valentin; Mudgal, Chaitanya S.] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM Dring@partners.org NR 18 TC 0 Z9 0 U1 0 U2 0 PU MASHHAD UNIV MED SCIENCES PI MASHHAD PA VICE-CHANCELLOR FOR RES CTR OFF IJBMS, DANESHGAH ST, PO BOX 9138813944 - 445, MASHHAD, 00000, IRAN SN 2345-4644 EI 2345-461X J9 ARCH BONE JT SURG-AB JI Arch. Bone Jt. Surg.-ABJS PD APR PY 2016 VL 4 IS 2 BP 150 EP 155 PG 6 WC Orthopedics SC Orthopedics GA DP7NG UT WOS:000378685500012 PM 27200394 ER PT J AU Kinaci, A Buijze, GA van Leeuwen, DH Jupiter, JB Marti, RK Kloen, P AF Kinaci, Ahmet Buijze, Geert A. van Leeuwen, Diederik H. Jupiter, Jesse B. Marti, Rene K. Kloen, Peter TI Corrective Osteotomy for Intra-Articular Distal Humerus Malunion SO ARCHIVES OF BONE AND JOINT SURGERY-ABJS LA English DT Article DE Distal humerus fracture; Distal humerus malunion; Intra-articular corrective osteotomy; Long-term follow-up ID FRACTURES; ELBOW; NONUNION; ADULTS; HEAD; END AB Background: An intra-articular distal humerus malunion can be disabling. To improve function, reduce pain and/or prevent further secondary osteoarthritis an intra-articular corrective osteotomy can be considered. Herein we present the indications, practical guidelines for pre-operative planning and surgical technique. Subsequently, we provide long-term results in a small series. Methods: We included six consecutive patients operated for intra-articular distal humerus malunion. Mean follow-up was 88 months. At lastest follow up elbow function was assessed according to standardized questionnaires and classification systems. Results: All six patients healed their osteotomies. Three patients had a postoperative complication which were treated succesfully. Range of motion improved significantly and all patients were satisfied with the outcome. The elbow performance scores were good to excellent in all. Correlation analyses showed that age and level of osteoarthritis are very strong predictors for the long-term elbow function and quality of life. Conclusion: An intra-articular corrective osteotomy for a malunited distal humerus fracture is a worthwhile procedure. Based on our results it should particularly be considered in young patients with minimal osteoarthritis and moderate to severe functional disability and/or pain. C1 [Kinaci, Ahmet; Buijze, Geert A.; van Leeuwen, Diederik H.; Jupiter, Jesse B.; Marti, Rene K.; Kloen, Peter] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kinaci, Ahmet; Buijze, Geert A.; van Leeuwen, Diederik H.; Jupiter, Jesse B.; Marti, Rene K.; Kloen, Peter] Acad Med Ctr, Amsterdam, Netherlands. [Kinaci, Ahmet; Buijze, Geert A.; Marti, Rene K.; Kloen, Peter] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [van Leeuwen, Diederik H.; Jupiter, Jesse B.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. RP Kinaci, A (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands. EM Akinaci@outlook.com NR 18 TC 0 Z9 0 U1 1 U2 1 PU MASHHAD UNIV MED SCIENCES PI MASHHAD PA VICE-CHANCELLOR FOR RES CTR OFF IJBMS, DANESHGAH ST, PO BOX 9138813944 - 445, MASHHAD, 00000, IRAN SN 2345-4644 EI 2345-461X J9 ARCH BONE JT SURG-AB JI Arch. Bone Jt. Surg.-ABJS PD APR PY 2016 VL 4 IS 2 BP 161 EP 165 PG 5 WC Orthopedics SC Orthopedics GA DP7NG UT WOS:000378685500014 PM 27200396 ER PT J AU Talcott, KE Eliott, D AF Talcott, Katherine E. Eliott, Dean TI Central Retinal Vein Occlusion Associated With Severe Vitamin D Deficiency SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA LA English DT Article ID SEASONAL-VARIATIONS; RISK; POPULATION; SWEDEN; ONSET AB Central retinal vein occlusion (CRVO) is thought to occur due to thrombotic occlusion of the central retinal vein at or just posterior to the lamina cribrosa. Studies have shown that the incidence of CRVO may be higher in winter to early spring, suggesting that low vitamin D levels may play a role; however, no studies have measured vitamin D levels in patients with CRVO. In addition, there is mounting evidence that patients with vitamin D deficiency may be predisposed to thrombotic events. The authors report a case of central retinal vein occlusion associated with marked vitamin D deficiency. C1 [Talcott, Katherine E.; Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Eliott, D (reprint author), Massachusetts Eye & Ear Infirm, Dept Retina, 243 Charles St, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2325-8160 EI 2325-8179 J9 OSLI RETINA JI Ophthalmic Surg. Lasers Imag. Retin. PD APR PY 2016 VL 47 IS 4 BP 372 EP 375 DI 10.3928/23258160-20160324-13 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DP9VJ UT WOS:000378845400013 PM 27065380 ER PT J AU Thanos, A Miller, JB Ma, KN Subramanian, ML Kim, IK Eliott, D AF Thanos, Aristomenis Miller, John B. Ma, Kelly N. Subramanian, Manju L. Kim, Ivana K. Eliott, Dean TI A New Variant of Polypoidal Choroidal Vasculopathy With Annular Pigmentary Changes in Haitian Males SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA LA English DT Article ID S-CONE SYNDROME AB The authors report a new variant of idiopathic polypoidal choroidal vasculopathy (IPCV) in middle-aged Haitian men characterized by extramacular polypoidal lesions and bilateral extensive pigmentary alterations in the posterior pole in an annular wreath-like pattern surrounding the optic nerve and macular area. Two patients were seen at Massachusetts Eye and Ear Infirmary and one at Boston University Medical Center between 2010 and 2015. All three patients were middle-aged Haitian men who exhibited bilateral features of IPCV, including subretinal hemorrhages and serosanguinous pigment epithelial detachments. Indocyanine green angiography revealed extramacular polypoidal lesions located mostly along the major vascular arcades. Extensive pigmentary alterations were evident in the posterior pole surrounding the macula and optic nerve in an annular wreath-like pattern. These cases further expand the clinical spectrum of IPCV. C1 [Thanos, Aristomenis; Miller, John B.; Kim, Ivana K.; Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. [Ma, Kelly N.; Subramanian, Manju L.] Boston Univ, Med Ctr, Dept Ophthalmol, Boston, MA USA. RP Eliott, D (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu NR 14 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2325-8160 EI 2325-8179 J9 OSLI RETINA JI Ophthalmic Surg. Lasers Imag. Retin. PD APR PY 2016 VL 47 IS 4 BP 381 EP 386 DI 10.3928/23258160-20160324-15 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DP9VJ UT WOS:000378845400015 PM 27065382 ER PT J AU Chen, SP Ay, I de Morais, AL Qin, T Zheng, Y Sadeghian, H Oka, F Simon, B Eikermann-Haerter, K Ayata, C AF Chen, Shih-Pin Ay, Ilknur de Morais, Andreia Lopes Qin, Tao Zheng, Yi Sadeghian, Homa Oka, Fumiaki Simon, Bruce Eikermann-Haerter, Katharina Ayata, Cenk TI Vagus nerve stimulation inhibits cortical spreading depression SO PAIN LA English DT Article DE Migraine; Cortical spreading depression; Vagus nerve stimulation ID HEMIPLEGIC MIGRAINE TYPE-1; FOCAL CEREBRAL-ISCHEMIA; ELECTRICAL-STIMULATION; LOCUS-COERULEUS; INTRACTABLE EPILEPSY; REFRACTORY EPILEPSY; POSSIBLE MECHANISM; MOUSE MODELS; RAT; PROPHYLAXIS AB Vagus nerve stimulation has recently been reported to improve symptoms of migraine. Cortical spreading depression is the electrophysiological event underlying migraine aura and is a trigger for headache. We tested whether vagus nerve stimulation inhibits cortical spreading depression to explain its antimigraine effect. Unilateral vagus nerve stimulation was delivered either noninvasively through the skin or directly by electrodes placed around the nerve. Systemic physiology was monitored throughout the study. Both noninvasive transcutaneous and invasive direct vagus nerve stimulations significantly suppressed spreading depression susceptibility in the occipital cortex in rats. The electrical stimulation threshold to evoke a spreading depression was elevated by more than 2-fold, the frequency of spreading depressions during continuous topical 1 M KCl was reduced by similar to 40%, and propagation speed of spreading depression was reduced by similar to 15%. This effect developed within 30 minutes after vagus nerve stimulation and persisted for more than 3 hours. Noninvasive transcutaneous vagus nerve stimulation was as efficacious as direct invasive vagus nerve stimulation, and the efficacy did not differ between the ipsilateral and contralateral hemispheres. Our findings provide a potential mechanism by which vagus nerve stimulation may be efficacious in migraine and suggest that susceptibility to spreading depression is a suitable platform to optimize its efficacy. C1 [Chen, Shih-Pin; de Morais, Andreia Lopes; Qin, Tao; Zheng, Yi; Sadeghian, Homa; Oka, Fumiaki; Eikermann-Haerter, Katharina; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA USA. [Chen, Shih-Pin] Taipei Vet Gen Hosp, Neurol Inst, Dept Neurol, Taipei 11217, Taiwan. [Chen, Shih-Pin] Natl Yang Ming Univ, Sch Med, Fac Med, Dept Neurol, Taipei 112, Taiwan. [Ay, Ilknur] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA. [Simon, Bruce] ElectroCore LLC, Basking Ridge, NJ USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Charlestown, MA USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit,Dept Neurol, Charlestown, MA USA. RP Chen, SP (reprint author), Taipei Vet Gen Hosp, Neurol Inst, Dept Neurol, Taipei 11217, Taiwan. EM chensp1977@gmail.com FU Taipei Veterans General Hospital-National Yang-Ming University Excellent Physician Scientists Cultivation Program [102-V-A-001]; American Heart Association [10SDG2610275, 10SDG2600218]; Massachusetts General Hospital (Claflin Distinguished Award) FX This work was funded in part by Taipei Veterans General Hospital-National Yang-Ming University Excellent Physician Scientists Cultivation Program (No. 102-V-A-001 to S.P.C.), the American Heart Association (10SDG2610275 to K.E.-H.; 10SDG2600218 to I.A.), the Massachusetts General Hospital (Claflin Distinguished Award to K.E.-H.), and an unrestricted research gift from electroCore LLC. NR 65 TC 8 Z9 8 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD APR PY 2016 VL 157 IS 4 BP 797 EP 805 DI 10.1097/j.pain.0000000000000437 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA DP1PJ UT WOS:000378261600007 PM 26645547 ER PT J AU Becerra, L Aasted, CM Boas, DA George, E Yucel, MA Kussman, BD Kelsey, P Borsook, D AF Becerra, Lino Aasted, Christopher M. Boas, David A. George, Edward Yuecel, Meryem A. Kussman, Barry D. Kelsey, Peter Borsook, David TI Brain measures of nociception using near-infrared spectroscopy in patients undergoing routine screening colonoscopy SO PAIN LA English DT Article DE Prefrontal cortex; Near-infrared spectroscopy; Sedation; Insufflation; Analgesia ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; PROPOFOL-INDUCED LOSS; VISCERAL PAIN; DEFAULT MODE; DESCENDING COLON; NITROUS-OXIDE; HEART-RATE; SEDATION AB Colonoscopy is an invaluable tool for the screening and diagnosis of many colonic diseases. For most colonoscopies, moderate sedation is used during the procedure. However, insufflation of the colon produces a nociceptive stimulus that is usually accompanied by facial grimacing/groaning while under sedation. The objective of this study was to evaluate whether a nociceptive signal elicited by colonic insufflation could be measured from the brain. Seventeen otherwise healthy patients (age 54.8 +/- 9.1; 6 female) undergoing routine colonoscopy (ie, no history of significant medical conditions) were monitored using near-infrared spectroscopy (NIRS). Moderate sedation was produced using standard clinical protocols for midazolam and meperidine, titrated to effect. Near-infrared spectroscopy data captured during the procedure was analyzed offline to evaluate the brains' responses to nociceptive stimuli evoked by the insufflation events (defined by physician or observing patients' facial responses). Analysis of NIRS data revealed a specific, reproducible prefrontal cortex activity corresponding to times when patients grimaced. The pattern of the activation is similar to that previously observed during nociceptive stimuli in awake healthy individuals, suggesting that this approach may be used to evaluate brain activity evoked by nociceptive stimuli under sedation, when there is incomplete analgesia. Although some patients report recollection of procedural pain after the procedure, the effects of repeated nociceptive stimuli in surgical patients may contribute to postoperative changes including chronic pain. The results from this study indicate that NIRS may be a suitable technology for continuous nociceptive afferent monitoring in patients undergoing sedation and could have applications under sedation or anesthesia. C1 [Becerra, Lino; Aasted, Christopher M.; Kussman, Barry D.; Borsook, David] Boston Childrens Hosp, PAIN Grp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Becerra, Lino; Aasted, Christopher M.; Borsook, David] Harvard Univ, Sch Med, Ctr Pain & Brain, Boston, MA USA. [Becerra, Lino; Boas, David A.; Yuecel, Meryem A.; Borsook, David] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [George, Edward] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Kelsey, Peter] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Becerra, L (reprint author), Boston Childrens Hosp, Ctr Pain & Brain, PAIN Grp, 9 Hope Ave, Boston, MA 02453 USA. EM lino.becerra@childrens.harvard.edu FU Center for Integration of Medicine and Innovative Technology; National Institutes of Health [R01-GM104986]; Mayday Foundation FX This work was supported by the Center for Integration of Medicine and Innovative Technology, the National Institutes of Health through R01-GM104986, and the Mayday Foundation. NR 51 TC 2 Z9 2 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD APR PY 2016 VL 157 IS 4 BP 840 EP 848 DI 10.1097/j.pain.0000000000000446 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA DP1PJ UT WOS:000378261600011 PM 26645550 ER PT J AU Guimaraes, AR Siqueira, L Uppal, R Alford, J Fuchs, BC Yamada, S Tanabe, K Chung, RT Lauwers, G Chew, ML Boland, GW Sahani, DV Vangel, M Hahn, PF Caravan, P AF Guimaraes, Alexander R. Siqueira, Luiz Uppal, Ritika Alford, Jamu Fuchs, Bryan C. Yamada, Suguru Tanabe, Kenneth Chung, Raymond T. Lauwers, Gregory Chew, Michael L. Boland, Giles W. Sahani, Duhyant V. Vangel, Mark Hahn, Peter F. Caravan, Peter TI T2 relaxation time is related to liver fibrosis severity SO QUANTITATIVE IMAGING IN MEDICINE AND SURGERY LA English DT Article DE MRI; liver fibrosis; quantitative imaging; T2 relaxation time; fibrosis imaging biomarkers ID CHRONIC HEPATITIS-C; MAGNETIC-RESONANCE ELASTOGRAPHY; HEPATOCELLULAR-CARCINOMA; TRANSIENT ELASTOGRAPHY; UNITED-STATES; NONINVASIVE ASSESSMENT; MR RELAXOMETRY; CIRRHOSIS; DIAGNOSIS; DISEASE AB Background: The grading of liver fibrosis relies on liver biopsy. Imaging techniques, including elastography and relaxometric, techniques have had varying success in diagnosing moderate fibrosis. The goal of this study was to determine if there is a relationship between the T2-relaxation time of hepatic parenchyma and the histologic grade of liver fibrosis in patients with hepatitis C undergoing both routine, liver MRI and liver biopsy, and to validate our methodology with phantoms and in a rat model of liver fibrosis. Methods: This study is composed of three parts: (I) 123 patients who underwent both routine, clinical liver MRI and biopsy within a 6-month period, between July 1999 and January 2010 were enrolled in a retrospective study. MR imaging was performed at 1.5 T using dual-echo turbo-spin echo equivalent pulse sequence. T2 relaxation time of liver parenchyma in patients was calculated by mono-exponential fit of a region of interest (ROI) within the right lobe correlating to histopathologic grading (Ishak 0-6) and routine serum liver inflammation [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. Statistical comparison was performed using ordinary logistic and ordinal logistic regression and ANOVA comparing T2 to Ishak fibrosis without and using AST and ALT as covariates; (II) a phantom was prepared using serial dilutions of dextran coated magnetic iron oxide nanoparticles. T2 weighed imaging was performed by comparing a dual echo fast spin echo sequence to a Carr-Purcell-Meigboom-Gill (CPMG) multi-echo sequence at 1.5 T. Statistical comparison was performed using a paired t-test; (III) male Wistar rats receiving weekly intraperitoneal injections of phosphate buffer solution (PBS) control (n= 4 rats); diethylnitrosamine (DEN) for either 5 (n= 5 rats) or 8 weeks (n= 4 rats) were MR imaged on a Bruker Pharmascan 4.7 T magnet with a home-built bird-cage coil. T2 was quantified by using a mono-exponential fitting algorithm on multi-slice multi echo T2 weighted data. Statistical comparison was performed using ANOVA. Results: (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4 +/- 2.9 ms, n= 6 patients); mild (Ishak 1-2) 66.7 +/- 1.9 ms (n= 30); moderate (Ishak 3-4) 71.6 +/- 1.7 ms (n= 26); severe (Ishak 5-6) 72.4 +/- 1.4 ms (n= 61); with relatively low standard error (similar to 2.9 ms). There was a statistically significant difference between degrees of mild (Ishak <4) vs. moderate to severe fibrosis (Ishak >4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA P<0.0001) between each rat subgroup [phosphate buffer solution (PBS) 25.2 +/- 0.8, DEN 5-week (31.1 +/- 1.5), and DEN 9-week (49.4 +/- 0.4) ms]; (III) the phantoms that had T2 values within the relevant range for the human liver (e.g., 20-100 ms), demonstrated no statistical difference between two point fits on turbo spin echo (TSE) data and multi-echo CPMG data (P=0.9). Conclusions: The finding of increased T2 with liver fibrosis may relate to inflammation that may be an alternative or adjunct to other noninvasive MR imaging based approaches for assessing liver fibrosis. C1 [Guimaraes, Alexander R.; Siqueira, Luiz; Chew, Michael L.; Boland, Giles W.; Sahani, Duhyant V.; Hahn, Peter F.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Guimaraes, Alexander R.; Uppal, Ritika; Alford, Jamu; Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Guimaraes, Alexander R.] Oregon Hlth & Sci Univ, Dept Radiol, Sect Body Imaging, Portland, OR 97239 USA. [Fuchs, Bryan C.; Yamada, Suguru; Tanabe, Kenneth] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Div Hepatol, Boston, MA 02114 USA. [Lauwers, Gregory] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Vangel, Mark] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Guimaraes, AR (reprint author), Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. EM guimaraa@ohsu.edu FU NIBIB NIH HHS [R01 EB009062]; NIDDK NIH HHS [R01 DK104956] NR 47 TC 0 Z9 0 U1 2 U2 3 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 2223-4292 EI 2223-4306 J9 QUANT IMAGING MED SU JI Quant. Imaging Med. Surg. PD APR PY 2016 VL 6 IS 2 BP 103 EP 114 DI 10.21037/qims.2016.03.02 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP6XT UT WOS:000378643800001 PM 27190762 ER PT J AU Szalat, R Munshi, NC AF Szalat, Raphael Munshi, Nikhil C. TI Genomic heterogeneity in multiple myeloma (vol 30, pg 56, 2015) SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Correction C1 [Szalat, Raphael; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA. RP Szalat, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2016 VL 37 BP 158 EP 158 DI 10.1016/j.gde.2016.02.003 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA DO8WX UT WOS:000378067300020 ER PT J AU Fey, M Morse, K Palaganas, J Rudolph, J Simon, R AF Fey, Mary Morse, Kate Palaganas, Janice Rudolph, Jenny Simon, Robert TI Untitled SO JOURNAL OF NURSING REGULATION LA English DT Letter C1 [Fey, Mary; Morse, Kate; Palaganas, Janice; Rudolph, Jenny; Simon, Robert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Med Simulat, Boston, MA USA. RP Fey, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Med Simulat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2155-8256 EI 2155-8264 J9 J NURS REGUL JI J. Nurs. Regul. PD APR PY 2016 VL 7 IS 1 BP 4 EP 4 AR PII S2155-8256(15)30783-3 PG 1 WC Nursing SC Nursing GA DP1PI UT WOS:000378261500002 ER PT J AU Jones, RB Mueller, S O'Connor, R Rimpel, K Sloan, DD Karel, D Wong, HC Jeng, EK Thomas, AS Whitney, JB Lim, SY Kovacs, C Benko, E Karandish, S Huang, SH Buzon, MJ Lichterfeld, M Irrinki, A Murry, JP Tsai, A Yu, H Geleziunas, R Trocha, A Ostrowski, MA Irvine, DJ Walker, BD AF Jones, R. Brad Mueller, Stefanie O'Connor, Rachel Rimpel, Katherine Sloan, Derek D. Karel, Dan Wong, Hing C. Jeng, Emily K. Thomas, Allison S. Whitney, James B. Lim, So-Yon Kovacs, Colin Benko, Erika Karandish, Sara Huang, Szu-Han Buzon, Maria J. Lichterfeld, Mathias Irrinki, Alivelu Murry, Jeffrey P. Tsai, Angela Yu, Helen Geleziunas, Romas Trocha, Alicja Ostrowski, Mario A. Irvine, Darrell J. Walker, Bruce D. TI A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4(+) T-Cells to Recognition by Cytotoxic T-Lymphocytes SO PLOS PATHOGENS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; IN-VIVO; EXPRESSION; IL-15; ACTIVATION; RESERVOIR; REACTIVATION; HEXAMETHYLBISACETAMIDE; IMMUNOTHERAPY; STIMULATION AB Resting CD4(+) T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8(+) T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8(+) T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8(+) T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8(+) T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8(+) T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam3CSK4. In contrast, we did not observe CD8(+) T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist 'ALT-803', an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8(+) T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8(+) T-cells in HIV eradication strategies. C1 [Jones, R. Brad; O'Connor, Rachel; Rimpel, Katherine; Karel, Dan; Thomas, Allison S.; Whitney, James B.; Buzon, Maria J.; Lichterfeld, Mathias; Trocha, Alicja; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Jones, R. Brad; O'Connor, Rachel; Rimpel, Katherine; Karel, Dan; Thomas, Allison S.; Whitney, James B.; Buzon, Maria J.; Lichterfeld, Mathias; Trocha, Alicja; Walker, Bruce D.] Harvard Univ, Cambridge, MA 02138 USA. [Jones, R. Brad; Mueller, Stefanie; Irvine, Darrell J.] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Jones, R. Brad; Thomas, Allison S.; Karandish, Sara; Huang, Szu-Han] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA. [Sloan, Derek D.; Irrinki, Alivelu; Murry, Jeffrey P.; Tsai, Angela; Yu, Helen; Geleziunas, Romas] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. [Wong, Hing C.; Jeng, Emily K.] Altor BioSci Corp, Miramar, FL USA. [Whitney, James B.; Lim, So-Yon] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Kovacs, Colin; Benko, Erika] Maple Leaf Med Clin, Toronto, ON, Canada. [Kovacs, Colin; Ostrowski, Mario A.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Ostrowski, Mario A.] St Michaels Hosp, Li Ka Shing Med Inst, 30 Bond St, Toronto, ON M5B 1W8, Canada. [Irvine, Darrell J.; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Irvine, Darrell J.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Walker, BD (reprint author), MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Walker, BD (reprint author), Howard Hughes Med Inst, Chevy Chase, MD USA. EM bwalker@mgh.harvard.edu FU NIH [AI111860]; Ragon Institute of MGH, MIT, and Harvard; GenerationCure initiative through the American Foundation for AIDS Research (amfAR) FX This work was supported in part by the NIH (AI111860) and the Ragon Institute of MGH, MIT, and Harvard. We also gratefully acknowledge financial support from the GenerationCure initiative through the American Foundation for AIDS Research (amfAR). During the time that this study was performed, RBJ was a Banting Fellow of the Canadian Institutes for Health Research and a Junior Investigator of the Ontario HIV Treatment Network. BDW and DJI are Investigators of the Howard Hughes Medical Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 8 Z9 8 U1 2 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2016 VL 12 IS 4 AR e1005545 DI 10.1371/journal.ppat.1005545 PG 25 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA DP0CZ UT WOS:000378156900030 PM 27082643 ER PT J AU Amiel, CR Blomberg, BB Gudenkauf, LM Diaz, A Lee, JS Jutagir, DR Bouchard, LC Stagl, JM Lechner, S Gluck, S Carver, CS Antoni, MH AF Amiel, Chelsea R. Blomberg, Bonnie B. Gudenkauf, Lisa M. Diaz, Alain Lee, Jasper S. Jutagir, Devika R. Bouchard, Laura C. Stagl, Jamie M. Lechner, Suzanne Gluck, Stefan Carver, Charles S. Antoni, Michael H. TI POSITIVE AFFECT AND EMOTIONAL WELL-BEING RELATE TO LESS PRO-INFLAMMATORY LEUKOCYTE GENE EXPRESSION IN DISTRESSED WOMEN WITH NON-METASTATIC BREAST CANCER AFTER SURGERY SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Amiel, Chelsea R.; Gudenkauf, Lisa M.; Lee, Jasper S.; Jutagir, Devika R.; Bouchard, Laura C.; Carver, Charles S.; Antoni, Michael H.] Univ Miami, Dept Psychol, POB 248185, Coral Gables, FL 33124 USA. [Blomberg, Bonnie B.; Diaz, Alain] Univ Miami, Dept Microbiol & Immunol, Miami, FL USA. [Stagl, Jamie M.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Lechner, Suzanne] Univ Miami, Dept Psychiat & Behav Sci, Miami, FL USA. [Gluck, Stefan] Celgene Corp, Breast Ovarian Bladder Canc & Immunooncol, Summit, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1452 BP A126 EP A127 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800409 ER PT J AU Amiel, CR Blomberg, BB Gudenkauf, L Diaz, A Lee, JS Jutagir, DR Bouchard, LC Stagl, JM Lechner, S Gluck, S Carver, CS Antoni, MH AF Amiel, Chelsea R. Blomberg, Bonnie B. Gudenkauf, Lisa Diaz, Alain Lee, Jasper S. Jutagir, Devika R. Bouchard, Laura C. Stagl, Jamie M. Lechner, Suzanne Gluck, Stefan Carver, Charles S. Antoni, Michael H. TI CHANGE IN PRO-INFLAMMATORY GENE EXPRESSION OVER 12-MONTHS PREDICTS FATIGUE SEVERITY IN DISTRESSED WOMEN WITH NON-METASTATIC BREAST CANCER SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Amiel, Chelsea R.; Gudenkauf, Lisa; Lee, Jasper S.; Jutagir, Devika R.; Bouchard, Laura C.; Lechner, Suzanne; Carver, Charles S.; Antoni, Michael H.] Univ Miami, Dept Psychol, POB 248185, Coral Gables, FL 33124 USA. [Blomberg, Bonnie B.; Diaz, Alain] Univ Miami, Dept Microbiol & Immunol, Miami, FL USA. [Stagl, Jamie M.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Gluck, Stefan] Celgene Corp, Breast Ovarian Bladder Canc & Immunooncol, Summit, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1670 BP A20 EP A20 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800065 ER PT J AU Antoni, MH Bouchard, L Stagl, J Gudenkauf, L Juatgir, D Lechner, S Carver, CS Carver, CS Lutgendorf, S Lippman, M Blomberg, B AF Antoni, Michael H. Bouchard, Laura Stagl, Jamie Gudenkauf, Lisa Juatgir, Devika Lechner, Suzanne Carver, Charles S. Cole, Steve Lutgendorf, Susan Lippman, Marc Blomberg, Bonnie TI REDUCTIONS IN LEUKOCYTE ADVERSITY-RELATED GENE EXPRESSION WITH STRESS MANAGEMENT DURING PRIMARY TREATMENT FOR BREAST CANCER PREDICT GREATER DISEASE FREE SURVIVAL AT 11YR FOLLOW-UP SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Antoni, Michael H.; Bouchard, Laura; Gudenkauf, Lisa; Juatgir, Devika; Carver, Charles S.] Univ Miami, Psychol, Coral Gables, FL 33124 USA. [Stagl, Jamie] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Lechner, Suzanne] Univ Miami, Sch Med, Psychiat, Miami, FL USA. [Cole, Steve] Univ Calif Los Angeles, Med, Los Angeles, CA USA. [Lutgendorf, Susan] Univ Iowa, Psychol, Iowa City, IA USA. [Lippman, Marc] Univ Miami, Sch Med, Med, Miami, FL USA. [Blomberg, Bonnie] Univ Miami, Sch Med, Microbiol Immunol, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1051 BP A41 EP A41 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800128 ER PT J AU Bouchard, LC Fisher, HM Stagl, JM Blomberg, BB Diaz, A Jutagir, DR Amiel, CR Gudenkauf, LM Lechner, S Carver, CS Lutgendorf, S Cole, SW Antoni, MH AF Bouchard, Laura C. Fisher, Hannah M. Stagl, Jamie M. Blomberg, Bonnie B. Diaz, Alain Jutagir, Devika R. Amiel, Chelsea R. Gudenkauf, Lisa M. Lechner, Suzanne Carver, Charles S. Lutgendorf, Susan Cole, Steve W. Antoni, Michael H. TI STRESS MANAGEMENT-ASSOCIATED REDUCTIONS IN PRO-METASTATIC AND PRO-INFLAMMATORY LEUKOCYTE GENE EXPRESSION PREDICT 11-YEAR RISK OF DEATH IN BREAST CANCER PATIENTS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Bouchard, Laura C.; Fisher, Hannah M.; Jutagir, Devika R.; Amiel, Chelsea R.; Gudenkauf, Lisa M.; Carver, Charles S.; Antoni, Michael H.] Univ Miami, Psychol, Coral Gables, FL 33124 USA. [Stagl, Jamie M.] Massachusetts Gen Hosp, Ctr Canc, Psychiat, Boston, MA USA. [Blomberg, Bonnie B.; Diaz, Alain] Univ Miami, Miller Sch Med, Microbiol & Immunol, Miami, FL 33136 USA. [Lechner, Suzanne] Univ Miami, Psychiat, Miami, FL USA. [Lutgendorf, Susan] Univ Iowa, Psychol, Iowa City, IA USA. [Cole, Steve W.] Univ Calif Los Angeles, Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1142 BP A36 EP A36 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800112 ER PT J AU Castro-Chapman, PL Yanson, J Orr, SP Pineles, SL Salomon, K AF Castro-Chapman, Paula L. Yanson, Jessica Orr, Scott P. Pineles, Suzanne L. Salomon, Kristen TI PTSD SYMPTOMS ARE RELATED TO BLUNTED CARDIOVASCULAR REACTIVITY TO TRAUMA-IMAGERY AND NON-TRAUMA TASKS AMONG OEF/OIF/OND VETERANS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Castro-Chapman, Paula L.] James A Haley VA, Res Serv, Tampa, FL USA. [Yanson, Jessica] Univ S Florida, Rehabil & Mental Hlth Counseling, Tampa, FL USA. [Orr, Scott P.] Massachusetts Gen Hosp, Psychiat, Charlestown, MA USA. [Pineles, Suzanne L.] Boston Univ, Sch Med, Psychiat, Boston, MA 02118 USA. [Salomon, Kristen] Univ S Florida, Psychol, Tampa, FL USA. FU Veterans Affairs Health Services Research and Development (HSRD) FX This research was partially funded by the Veterans Affairs Health Services Research and Development (HSRD) supplemental funds and with resources from James A Haley VA, Research Department. This research was approved by the USF IRB. The views expressed herein are solely those of the authors and do not represent the views of the Department of Veteran Affairs or the University of South Florida. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1659 BP A79 EP A80 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800247 ER PT J AU Celano, CM Beale, EE Beach, SR Belcher, AM Suarez, L Motiwala, SR Gandhi, PU Gaggin, H Januzzi, JL Healy, BC Huffman, JC AF Celano, Christopher M. Beale, Eleanor E. Beach, Scott R. Belcher, Arianna M. Suarez, Laura Motiwala, Shweta R. Gandhi, Parul U. Gaggin, Hanna Januzzi, James L. Healy, Brian C. Huffman, Jeff C. TI ASSOCIATIONS BETWEEN PSYCHOLOGICAL CONSTRUCTS AND CARDIAC BIOMARKERS AFTER AN ACUTE CORONARY SYNDROME SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Celano, Christopher M.; Beach, Scott R.; Huffman, Jeff C.] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Beale, Eleanor E.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Belcher, Arianna M.] Massachusetts Gen Hosp, Med, Boston, MA 02114 USA. [Suarez, Laura] Mayo Clin, Psychiat, Rochester, MN USA. [Motiwala, Shweta R.] Beth Israel Deaconess Med Ctr, Med, Boston, MA 02215 USA. [Gandhi, Parul U.] Yale Univ, Sch Med, Med, New Haven, CT USA. [Gaggin, Hanna; Januzzi, James L.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Healy, Brian C.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1147 BP A22 EP A22 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800072 ER PT J AU Gibson, C Thurston, R Matthews, K AF Gibson, Carolyn Thurston, Rebecca Matthews, Karen TI DAILY ASSOCIATIONS BETWEEN DIARY-REPORTED HOT FLASHES AND CORTISOL SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Gibson, Carolyn] San Francisco VA Med Ctr, San Francisco, CA USA. [Thurston, Rebecca; Matthews, Karen] Univ Pittsburgh, Psychol, Psychiat, Epidemiol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1079 BP A47 EP A47 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800149 ER PT J AU Gudenkauf, LM Wang, A Bouchard, L Jutagir, D Amiel, C Stagl, J Lechner, S Blomberg, B Carver, C Antoni, M AF Gudenkauf, Lisa M. Wang, Ashley Bouchard, Laura Jutagir, Devika Amiel, Chelsea Stagl, Jamie Lechner, Suzanne Blomberg, Bonnie Carver, Charles Antoni, Michael TI BRIEF 5-WEEK COGNITIVE BEHAVIORAL AND RELAXATION TRAINING INTERVENTIONS DEMONSTRATE COMPARABLE INCREASES IN BENEFIT FINDING TO 10-WEEK CBSM INTERVENTION AMONG POST-SURGICAL BREAST CANCER PATIENTS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Gudenkauf, Lisa M.; Wang, Ashley; Bouchard, Laura; Jutagir, Devika; Carver, Charles; Antoni, Michael] Univ Miami, Psychol, Miami, FL USA. [Amiel, Chelsea] Univ Miami, Psychol, Coral Gables, FL 33124 USA. [Stagl, Jamie] Massachusetts Gen Hosp, Ctr Canc, Psychiat, Boston, MA USA. [Lechner, Suzanne] Univ Miami, Miller Sch Med, Psychiat, Miami, FL 33136 USA. [Blomberg, Bonnie] Univ Miami, Miller Sch Med, Microbiol & Immunol, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1297 BP A126 EP A126 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800407 ER PT J AU Harris, KM Anderson, DR Landers, JD Emery, CF AF Harris, Kristie M. Anderson, Derek R. Landers, Jacob D. Emery, Charles F. TI COPING STYLE AND DESIRE FOR TREATMENT AMONG PATIENTS IN OUTPATIENT CARDIAC REHABILITATION SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Harris, Kristie M.; Landers, Jacob D.; Emery, Charles F.] Ohio State Univ, Psychol, Columbus, OH 43210 USA. [Anderson, Derek R.] Vet Affairs Puget Sound Healthcare Syst, Rehabil Care Serv, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1292 BP A57 EP A57 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800176 ER PT J AU Huffman, J DuBois, C Millstein, R Celano, C Wexler, D AF Huffman, Jeff DuBois, Christina Millstein, Rachel Celano, Chris Wexler, Deborah TI A POSITIVE PSYCHOLOGICAL INTERVENTION FOR PATIENTS WITH TYPE 2 DIABETES SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Huffman, Jeff; DuBois, Christina; Millstein, Rachel; Celano, Chris] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Wexler, Deborah] Massachusetts Gen Hosp, Internal Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1363 BP A133 EP A133 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800430 ER PT J AU Huffman, J Beale, E Albanese, A Park, E AF Huffman, Jeff Beale, Eleanor Albanese, Ariana Park, Elyse TI RELATIONSHIPS BETWEEN POSITIVE PSYCHOLOGICAL CONSTRUCTS AND HEALTH BEHAVIORS IN TYPE 2 DIABETES: A QUALITATIVE STUDY SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Huffman, Jeff; Beale, Eleanor; Albanese, Ariana; Park, Elyse] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1369 BP A108 EP A108 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800345 ER PT J AU Jutagir, DR Bouchard, LC Amiel, CR Blomberg, BB Gudenkauf, LM Stagl, JM Carver, CS Lechner, SC Diaz, A Lutgendorf, S Cole, SW Antoni, MH AF Jutagir, Devika R. Bouchard, Laura C. Amiel, Chelsea R. Blomberg, Bonnie B. Gudenkauf, Lisa M. Stagl, Jamie M. Carver, Charles S. Lechner, Suzanne C. Diaz, Alain Lutgendorf, Susan Cole, Steve W. Antoni, Michael H. TI SOCIAL WELL-BEING IS ASSOCIATED WITH PRO-INFLAMMATORY AND PRO-METASTATIC LEUKOCYTE GENE EXPRESSION AFTER SURGERY FOR BREAST CANCER SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Jutagir, Devika R.; Bouchard, Laura C.; Amiel, Chelsea R.; Gudenkauf, Lisa M.; Carver, Charles S.; Antoni, Michael H.] Univ Miami, Psychol, Coral Gables, FL 33124 USA. [Blomberg, Bonnie B.; Diaz, Alain] Univ Miami, Miller Sch Med, Microbiol & Immunol, Miami, FL 33136 USA. [Stagl, Jamie M.] Massachusetts Gen Hosp, Ctr Canc, Psychiat Oncol & Behav Sci, Boston, MA USA. [Lechner, Suzanne C.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Lutgendorf, Susan] Univ Iowa, Psychol, Iowa City, IA USA. [Cole, Steve W.] Univ Calif Los Angeles, Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1088 BP A125 EP A125 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800405 ER PT J AU Millstein, RA Celano, CM Beach, SR Beale, EE Belcher, AA Huffman, JC AF Millstein, Rachel A. Celano, Christopher M. Beach, Scott R. Beale, Eleanor E. Belcher, Arianna A. Huffman, Jeff C. TI THE EFFECTS OF OPTIMISM AND GRATITUDE ON ADHERENCE, FUNCTIONING, AND MENTAL HEALTH FOLLOWING AN ACUTE CORONARY SYNDROME SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Millstein, Rachel A.; Celano, Christopher M.; Beach, Scott R.; Beale, Eleanor E.; Huffman, Jeff C.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Belcher, Arianna A.] Massachusetts Gen Hosp, Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1118 BP A83 EP A83 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800260 ER PT J AU Raggio, GA Sexton, M Authier, C Rauch, SM AF Raggio, Greer A. Sexton, Minden Authier, Caitlin Rauch, Sheila M. TI EXAMINING TRAUMA TYPE AND GENDER AS PREDICTORS OF SOMATIC SYMPTOMATOLOGY AMONG TREATMENT-SEEKING MILITARY VETERANS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Raggio, Greer A.] VA Boston Healthcare Syst, Behav Med, Psychol, Boston, MA USA. [Sexton, Minden; Authier, Caitlin] VA Ann Arbor Healthcare Syst, Mental Hlth, Ann Arbor, MI USA. [Rauch, Sheila M.] Emory Healthcare, Emory Vet Program, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1473 BP A109 EP A110 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800352 ER PT J AU Smith, BN Taverna, EC Tyzik, AL Fox, AB Vogt, D AF Smith, Brian N. Taverna, Emily C. Tyzik, Anna L. Fox, Annie B. Vogt, Dawne TI THE ROLES OF PTSD, DEPRESSION, AND ALCOHOL MISUSE IN LINKING MILITARY STRESSORS AND HEALTH-RELATED QUALITY OF LIFE IN MALE AND FEMALE VETERANS OF THE WARS IN IRAQ AND AFGHANISTAN SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Smith, Brian N.; Taverna, Emily C.; Fox, Annie B.; Vogt, Dawne] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Smith, Brian N.; Vogt, Dawne] VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. [Smith, Brian N.; Vogt, Dawne] Boston Univ, Sch Med, Boston, MA 02118 USA. [Tyzik, Anna L.] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1545 BP A48 EP A49 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800152 ER PT J AU Trudel-Fitzgerald, C Zhou, ES Poole, EM Zhang, XH Tworoger, SS Schernhammer, E AF Trudel-Fitzgerald, Claudia Zhou, Eric S. Poole, Elizabeth M. Zhang, Xhuehong Tworoger, Shelley S. Schernhammer, Eva TI SLEEP DURATION AND DIFFICULTY IN RELATION TO BREAST CANCER SURVIVAL: RESULTS FROM THE NURSES' HEALTH STUDY SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Trudel-Fitzgerald, Claudia] Harvard Univ, Social & Behav Sci, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Zhou, Eric S.; Poole, Elizabeth M.; Zhang, Xhuehong; Tworoger, Shelley S.; Schernhammer, Eva] Harvard Univ, Sch Med, Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Med, Boston, MA 02115 USA. [Zhou, Eric S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Poole, Elizabeth M.; Zhang, Xhuehong; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Tworoger, Shelley S.] Harvard Univ, Epidemiol, Sch Med, Boston, MA USA. [Tworoger, Shelley S.; Schernhammer, Eva] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Schernhammer, Eva] Med Univ Vienna, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1339 BP A100 EP A100 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800320 ER PT J AU Tyzik, AL Wachen, JS Niles, B Spiro, A King, L King, D Smith, BN AF Tyzik, Anna L. Wachen, Jennifer S. Niles, Barbara Spiro, Avron King, Lynda King, Daniel Smith, Brian N. TI PTSD SYMPTOM SEVERITY AS A RISK MECHANISM LINKING COMBAT EXPOSURE TO POST-DEPLOYMENT PHYSICAL HEALTH IN GULF WAR VETERANS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Tyzik, Anna L.] Boston Univ, Epidemiol, Boston, MA 02215 USA. [Wachen, Jennifer S.; Niles, Barbara; King, Lynda; King, Daniel; Smith, Brian N.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wachen, Jennifer S.; Niles, Barbara; King, Lynda; King, Daniel; Smith, Brian N.] VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. [Wachen, Jennifer S.; Niles, Barbara; Smith, Brian N.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiro, Avron] VA Boston Healthcare Syst, Epidemiol & Psychiat, Boston, MA USA. [King, Lynda; King, Daniel] VA Boston Healthcare Syst, Dept Psychol, Boston, MA USA. [King, Lynda; King, Daniel] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1559 BP A66 EP A66 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800208 ER PT J AU Walsh, CM Patel, N Walker, K Ruoff, L Varbel, J Wynn, M Miller, BL Neylan, TC Kramer, JH AF Walsh, Christine M. Patel, Nihar Walker, Kathleen Ruoff, Leslie Varbel, Jonathan Wynn, Matthew Miller, Bruce L. Neylan, Thomas C. Kramer, Joel H. TI The cognitive effects of disrupted sleep in healthy older adults SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Walsh, Christine M.; Patel, Nihar; Walker, Kathleen; Wynn, Matthew; Miller, Bruce L.; Kramer, Joel H.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Ruoff, Leslie; Varbel, Jonathan; Neylan, Thomas C.] San Francisco VA Med Ctr, Stress & Hlth Res, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1442 BP A18 EP A19 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800064 ER PT J AU Wang, AW Amiel, CR Bouchard, LC Gudenkauf, LM Jutagir, DR Fisher, HM Stagl, JM Blomberg, BB Diaz, A Lechner, S Carver, CS Antoni, MH AF Wang, Ashley W. Amiel, Chelsea R. Bouchard, Laura C. Gudenkauf, Lisa M. Jutagir, Devika R. Fisher, Hannah M. Stagl, Jamie M. Blomberg, Bonnie B. Diaz, Alain Lechner, Suzanne Carver, Charles S. Antoni, Michael H. TI COGNITIVE BEHAVIORAL STRESS MANAGEMENT EFFECTS ON MOOD IN BREAST CANCER PATIENTS PRESENTING WITH ELEVATED CANCER-SPECIFIC DISTRESS IN THE WEEKS AFTER SURGERY SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 74th Annual Meeting of the American-Psychosomatic-Society CY MAR 09-12, 2015 CL Denver, CO SP Amer Psychosomat Soc C1 [Wang, Ashley W.] Univ Miami, Psychol, Miami, FL USA. [Amiel, Chelsea R.; Bouchard, Laura C.; Gudenkauf, Lisa M.; Jutagir, Devika R.; Fisher, Hannah M.; Carver, Charles S.; Antoni, Michael H.] Univ Miami, Dept Psychol, Miami, FL USA. [Stagl, Jamie M.] Massachusetts Gen Hosp, Ctr Canc, Dept Psychiat, Boston, MA USA. [Blomberg, Bonnie B.; Diaz, Alain] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Blomberg, Bonnie B.; Lechner, Suzanne] Univ Miami, Miller Sch Med, Sylvester Canc Ctr, Miami, FL 33136 USA. [Lechner, Suzanne] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Carver, Charles S.; Antoni, Michael H.] Univ Miami, Sylvester Canc Ctr, Miami, FL USA. [Carver, Charles S.; Antoni, Michael H.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 MA 1268 BP A40 EP A41 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FX UT WOS:000373949800127 ER PT J AU Gerstner, ER Jain, RK Batchelor, TT AF Gerstner, Elizabeth R. Jain, Rakesh K. Batchelor, Tracy T. TI Value of correlative biomarkers in understanding tumor biology SO TRANSLATIONAL CANCER RESEARCH LA English DT Letter ID GLIOBLASTOMA; SURVIVAL C1 [Gerstner, Elizabeth R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Ctr Canc, Boston, MA 02114 USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Boston, MA 02114 USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM egerstner@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 1 U2 3 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 2218-676X EI 2219-6803 J9 TRANSL CANCER RES JI Transl. Cancer Res. PD APR PY 2016 VL 5 IS 2 BP 211 EP 212 DI 10.21037/tcr.2016.03.10 PG 2 WC Oncology SC Oncology GA DP0AQ UT WOS:000378150400024 ER PT J AU Redmann, M Darley-Usmar, V Zhang, JH AF Redmann, Matthew Darley-Usmar, Victor Zhang, Jianhua TI The Role of Autophagy, Mitophagy and Lysosomal Functions in Modulating Bioenergetics and Survival in the Context of Redox and Proteotoxic Damage: Implications for Neurodegenerative Diseases SO AGING AND DISEASE LA English DT Review DE oxidative stress; reductive stress; mitochondrial dysfunction; prions; alpha-synuclein; neurodegenerative diseases ID EXTENDS LIFE-SPAN; LIPOFUSCINOSES BATTEN-DISEASE; MITOCHONDRIAL QUALITY-CONTROL; CUZN-SUPEROXIDE-DISMUTASE; D-DEFICIENT MICE; OXIDATIVE STRESS; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; REACTIVE OXYGEN AB Redox and proteotoxic stress contributes to age-dependent accumulation of dysfunctional mitochondria and protein aggregates, and is associated with neurodegeneration. The free radical theory of aging inspired many studies using reactive species scavengers such as alpha-tocopherol, ascorbate and coenzyme Q to suppress the initiation of oxidative stress. However, clinical trials have had limited success in the treatment of neurodegenerative diseases. We ascribe this to the emerging literature which suggests that the oxidative stress hypothesis does not encompass the role of reactive species in cell signaling and therefore the interception with reactive species with antioxidant supplementation may result in disruption of redox signaling. In addition, the accumulation of redox modified proteins or organelles cannot be reversed by oxidant intercepting antioxidants and must then be removed by alternative mechanisms. We have proposed that autophagy serves this essential function in removing damaged or dysfunctional proteins and organelles thus preserving neuronal function and survival. In this review, we will highlight observations regarding the impact of autophagy regulation on cellular bioenergetics and survival in response to reactive species or reactive species generating compounds, and in response to proteotoxic stress. C1 [Redmann, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Redmann, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL 35294 USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM zhanja@uab.edu FU [NIHR01-NS064090] FX This work was supported by NIHR01-NS064090 (to JZ). NR 149 TC 7 Z9 7 U1 6 U2 11 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 APR PY 2016 VL 7 IS 2 BP 150 EP 162 DI 10.14336/AD.2015.0820 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA DO5BD UT WOS:000377797700006 PM 27114848 ER PT J AU Yamada, A Sato, KK Kinuhata, S Uehara, S Endo, G Hikita, Y Fujimoto, WY Boyko, EJ Hayashi, T AF Yamada, Akiko Sato, Kyoko K. Kinuhata, Shigeki Uehara, Shinichiro Endo, Ginji Hikita, Yonezo Fujimoto, Wilfred Y. Boyko, Edward J. Hayashi, Tomoshige TI Association of Visceral Fat and Liver Fat With Hyperuricemia SO ARTHRITIS CARE & RESEARCH LA English DT Article ID URIC-ACID LEVEL; X-RAY ABSORPTIOMETRY; HIGH BLOOD-PRESSURE; INSULIN-RESISTANCE; COMPUTED-TOMOGRAPHY; METABOLIC SYNDROME; HEART-DISEASE; METAANALYSIS; GOUT; MEN AB Objective. To examine cross-sectionally whether intraabdominal fat area (IAFA), i.e., visceral fat, and liver fat assessed by computed tomography (CT) are independently associated with hyperuricemia. Methods. Subjects were 801 Japanese men not taking antidiabetic, antihypertensive, or urate-lowering medications, without any history of renal disease, cardiovascular disease, or cancer, and with serum creatinine <1.5 mg/dl. Abdominal, thoracic, and thigh fat areas were measured by CT. Total fat area (TFA) was the sum of these fat areas. Total subcutaneous fat area (TSFA) was TFA minus IAFA. Liver fat was assessed by liver-to-spleen (L/S) ratio measured by CT. Hyperuricemia was defined as serum uric acid level >7.0 mg/dl. Its association with adiposity was tested using logistic regression. Results. The prevalence of hyperuricemia was 19.6% (157 men). Both greater IAFA and lower L/S ratio were independently associated with hyperuricemia in models that simultaneously included IAFA and L/S ratio: multiple-adjusted odds ratios of hyperuricemia for quintiles 3, 4, and 5 of IAFA were 2.16 (95% confidence interval [95% CI] 1.02-4.59), 2.41 (95% CI 1.13-5.16), and 4.00 (95% CI 1.81-8.85), respectively, compared to quintile 1, and the L/S ratios for quintiles 3, 2, and 1 were 2.34 (95% CI 1.16-4.75), 2.15 (95% CI 1.06-4.34), and 2.79 (95% CI 1.35-5.76), respectively, compared to quintile 5. Both IAFA and L/S ratio remained significant even after adjusting for abdominal subcutaneous fat area, TFA, TSFA, body mass index, or waist circumference. Of all fat measurements, IAFA had the strongest association with hyperuricemia by Akaike's information criteria. Conclusion. Greater amounts of both visceral fat and liver fat were independently associated with hyperuricemia. C1 [Yamada, Akiko; Sato, Kyoko K.; Kinuhata, Shigeki; Uehara, Shinichiro; Endo, Ginji; Hayashi, Tomoshige] Osaka City Univ, Grad Sch Med, Osaka 558, Japan. [Hikita, Yonezo] Ohtori Hlth Promot Ctr, Sakai, Osaka, Japan. [Fujimoto, Wilfred Y.; Boyko, Edward J.; Hayashi, Tomoshige] Univ Washington, Seattle, WA 98195 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Hayashi, T (reprint author), Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Abeno Ku, 1-4-3 Asahi Machi, Osaka 5458585, Japan. EM thayashi@med.osaka-cu.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology [17390177, 20390187, 23390177]; VA Puget Sound Health Care System FX Supported by Grants-in-Aid for Scientific Research (17390177, 20390187, 23390177) from the Ministry of Education, Culture, Sports, Science and Technology, and by the Ohtori Health Promotion Center, which provided facilities and services.; Dr. Boyko's work was supported by the VA Puget Sound Health Care System. NR 41 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD APR PY 2016 VL 68 IS 4 BP 553 EP 561 DI 10.1002/acr.22729 PG 9 WC Rheumatology SC Rheumatology GA DO6OG UT WOS:000377902400017 PM 26414410 ER PT J AU Mechanick, JI Harrell, RM Allende-Vigo, MZ Alvayero, C Arita-Melzer, O Aschner, P Camacho, PM Castillo, RZ Cerdas, S Coutinho, WF Davidson, JA Garber, JR Garvey, WT Gonzalez, FJL Granados, DO Hamdy, O Handelsman, Y Jimenez-Navarrete, MF Lupo, MA Mendoza, EJ Jimenez-Montero, JG Zangeneh, F AF Mechanick, Jeffrey I. Harrell, R. Mack Allende-Vigo, Myriam Z. Alvayero, Carlos Arita-Melzer, Onix Aschner, Pablo Camacho, Pauline M. Zacarias Castillo, Rogelio Cerdas, Sonia Coutinho, Walmir F. Davidson, Jaime A. Garber, Jeffrey R. Garvey, W. Timothy Lavalle Gonzalez, Fernando Javier Granados, Denis O. Hamdy, Osama Handelsman, Yehuda Francisco Jimenez-Navarrete, Manuel Lupo, Mark A. Mendoza, Enrique J. Jimenez-Montero, Jose G. Zangeneh, Farhad TI TRANSCULTURALIZATION RECOMMENDATIONS FOR DEVELOPING LATIN AMERICAN CLINICAL PRACTICE ALGORITHMS IN ENDOCRINOLOGY - PROCEEDINGS OF THE 2015 PAN-AMERICAN WORKSHOP BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY SO ENDOCRINE PRACTICE LA English DT Article ID DIFFERENTIATED THYROID-CANCER; NUTRITION ALGORITHM; PRACTICE GUIDELINES; NONCOMMUNICABLE DISEASES; STANDARDIZED PRODUCTION; OBESITY PREVALENCE; POSITION STATEMENT; RISK-ASSESSMENT; MEXICAN ADULTS; STAGING SYSTEM AB The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale. C1 [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Metab Support Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. [Harrell, R. Mack] Mem Ctr Integrat Endocrine Surg Hollywood, Hollywood, FL USA. [Allende-Vigo, Myriam Z.] Univ Puerto Rico, Sch Med, Med, San Juan, PR 00936 USA. [Allende-Vigo, Myriam Z.] Univ Hosp San Juan Puerto Rico, Endocrinol Sect, San Juan, PR USA. [Allende-Vigo, Myriam Z.] AACE Puerto Rico Chapter, San Juan, PR USA. [Alvayero, Carlos] Inst Salvadoreno Corazon, Unidad Diagnost Osteoporosis, San Salvador, El Salvador. [Arita-Melzer, Onix] Hosp Bendana, Int Med & Endocrinol, Honduras, CA USA. [Arita-Melzer, Onix] Hosp Bendana, Diabet & Risk Factors, Honduras, CA USA. [Arita-Melzer, Onix] Hosp Bendana, Honduras, CA USA. [Aschner, Pablo] Javeriana Univ, Colombian Diabet Assoc, Bogota, Colombia. [Aschner, Pablo] Javeriana Univ, Endocrinol & Clin Epidemiol, Bogota, Colombia. [Aschner, Pablo] San Ignacio Univ Hosp, Bogota, Colombia. [Camacho, Pauline M.] Loyola Univ, Med Ctr, Med, 2160 S 1st Ave, Maywood, IL 60153 USA. [Camacho, Pauline M.] Loyola Univ, Osteoporosis & Metab Bone Dis Ctr, Maywood, IL 60153 USA. [Zacarias Castillo, Rogelio] Hosp Gen Dr Manuel Gea Gonzalez, Med Div Internal Med, Internal, Mexico City, DF, Mexico. [Cerdas, Sonia; Jimenez-Montero, Jose G.] Hosp Cima, Div Endocrinol, San Jose, Costa Rica. [Zacarias Castillo, Rogelio] San Agustin Res Ctr San Jose, San Jose, Costa Rica. [Coutinho, Walmir F.] Pontificia Univ Catolica Rio de Janeiro, State Inst Diabet & Endocrinol, Rio De Janeiro, Brazil. [Davidson, Jaime A.] Univ Texas SW Med Ctr Dallas, Med, Touchstone Diabet Ctr, Dallas, TX USA. [Garber, Jeffrey R.] Beth Israel Deaconess Med Ctr Boston, Div Endocrinol, Harvard Vanguard Med Associates, Div Endocrine, Boston, MA USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Univ Alabama Birmingham, UAB Diabet Res Ctr, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr Birmingham, Birmingham, AL USA. [Lavalle Gonzalez, Fernando Javier] UANL, Fac Med, Nutr, Endocrinol,Internal Med, Nuevo Leon, Mexico. [Lavalle Gonzalez, Fernando Javier] UANL, Univ Hosp, Serv Endocrinol, Nuevo Leon, Mexico. [Lavalle Gonzalez, Fernando Javier] UANL, Hosp Univ Dr Jose E Gonzalez, Diabet Clin, Nuevo Leon, Mexico. [Lavalle Gonzalez, Fernando Javier] ISSSTE Monterrey, Policy Coordinating Grp Treatment Diabet, Official Mexican Standar State Program, Nuevo Leon, Mexico. [Lavalle Gonzalez, Fernando Javier] Hlth Eating & Phys Activ Monterrey, Nuevo Leon, Mexico. [Granados, Denis O.] Hosp Metropolitano Vivian Pellas, Hosp Aleman Nicaraguense, Internal Med & Endocrinol, Managua, Nicaragua. [Granados, Denis O.] Univ Nacl Autonoma Nicaragua Managua, Endocrinol & Internal Med, Managua, Nicaragua. [Hamdy, Osama] Harvard Univ, Med Sch Boston, Joslin Diabet Ctr, Obes Clin Program, Cambridge, MA 02138 USA. [Hamdy, Osama] Harvard Univ, Med Sch Boston, Joslin Diabet Ctr, Inpatient Diabet Program, Cambridge, MA 02138 USA. [Handelsman, Yehuda] Metab Inst Amer Tarzana, Tarzana, CA USA. [Francisco Jimenez-Navarrete, Manuel] Costa Rican Assoc Endocrinologists ANPEDEM, San Jose, Costa Rica. [Francisco Jimenez-Navarrete, Manuel] Univ Costa Rica, Endocrinol & Internal Med, San Jose, Costa Rica. [Francisco Jimenez-Navarrete, Manuel] Hosp San Vicente de Paul, Dept Endocrinol, San Jose, Costa Rica. [Lupo, Mark A.] Thyroid & Endocrine Ctr Florida, Sarasota, FL USA. [Lupo, Mark A.] Florida State Univ, Coll Med, Sarasota, FL USA. [Mendoza, Enrique J.] Univ Panama, Dean Sch Med, Biochem & Nutr, Panama City, Panama. [Jimenez-Montero, Jose G.] Univ Ciencias Med, Med, San Jose, Costa Rica. [Jimenez-Montero, Jose G.] Univ Ciencias Med, Post Grad Studies, San Jose, Costa Rica. [Zangeneh, Farhad] Endocrine Diabet & Osteoporosis Clin EDOC, Sterling, VA USA. RP Mechanick, JI (reprint author), Amer Assoc Clin Endocrinologists, 245 Riverside Ave,Suite 200, Jacksonville, FL 32202 USA. EM publications@aace.com FU Amgen; Eli Lilly; Boehringer Ingelheim; Daiichi-Sankyo; Eisai; Janssen; Liposcience; Novo Nordisk; Vivus, Inc.; Metagenics, Inc; USDA Dairy Council; Amarin; AstraZeneca; Bristol-Myers Squibb; Essperion; Frifolis; GlaxoSmithKline; Hamni; Intarcia; Lexicon; Eli Lilly Co; Merck; Pfizer; Regeneron; Sanofi; Takeda FX Dr. Pauline Camacho has received research grants from Amgen and Eli Lilly and has served on the advisory board for Amgen.; Dr. W. Timothy Garvey has received consultant fees from Boehringer Ingelheim, Daiichi-Sankyo, Eisai, Janssen, Liposcience, Novo Nordisk, and Vivus, Inc. He was principal investigator for contracted research for Amylin, AstraZeneca, Eisai, Elcelyx, Lexicon, Merck, Novo Nordisk, Pfizer, Sanofi, and Weight Watchers and is a stockholder for Bristol-Myers Squibb, ISIS, Lilly, Merck, Novartis, and Pfizer.; Dr. Osama Hamdy has received research support from Metagenics, Inc and the USDA Dairy Council and has served on the advisory board for AstraZeneca and Novo Nordisk.; Dr. Yehuda Handelsman has received research grant support, been a consultant for, and received speaker honoraria from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eisai, Essperion, Frifolis, GlaxoSmithKline, Hamni, Intarcia, Janssen, Lexicon, Eli Lilly & Co, Merck, Novo Nordisk, Pfizer, Regeneron, Sanofi, Takeda, and Vivus, Inc. He is also the Immediate Past President of the American College of Endocrinology. NR 115 TC 2 Z9 3 U1 2 U2 2 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 APR PY 2016 VL 22 IS 4 BP 476 EP 501 DI 10.4158/EP161229.GL PG 26 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO7NK UT WOS:000377969100013 PM 27031655 ER PT J AU Chader, GJ Young, M AF Chader, Gerald J. Young, Michael TI Preface: Sight Restoration Through Stem Cell Therapy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE ORSF; sight restoration; stem cell therapy AB This publication presents chapters based on a meeting entitled "Sight Restoration Through Stem Cell Therapy'' held on June 13, 2015, in Santa Monica, CA, sponsored by the Ocular Research Symposia Foundation (ORSF). It was chaired by Michael Young, PhD, Harvard Medical School, and Gerald Chader, PhD, University of Southern California. The mission of this publication and of the ORSF in general is to focus attention on unmet medical needs and current research opportunities in eye research with the objective of accelerating translation of research findings to effective clinical care. In the meeting, new research advances on stem cells and opportunities for their clinical application were highlighted and are recounted in the following chapters of this publication. By identifying "low-hanging fruit'' (i.e., the best opportunities for successful transition of laboratory research to prevention and new treatments and cures for ocular diseases), we seek to spur funding at both the basic research and clinical levels, resulting in sight-saving and sight-restoration measures in the near future. C1 [Chader, Gerald J.] USC Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA. [Young, Michael] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA USA. RP Chader, GJ (reprint author), USC Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA. EM gchader02040@gmail.com FU California Institute for Regenerative Medicine FX Supported in part by a grant from the California Institute for Regenerative Medicine for which the ORSF is very grateful. There was no commercial support for the meeting; therefore, we believe that the advice and recommendations provided by the meeting participants and reported in this volume are free of possible bias. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2016 VL 57 IS 5 SI SI DI 10.1167/iovs.16-19125 PG 5 WC Ophthalmology SC Ophthalmology GA DO8NC UT WOS:000378039300001 ER PT J AU Myers, EA Smith, DA Allen, SR Kaplan, LJ AF Myers, Elizabeth A. Smith, David A. Allen, Steven R. Kaplan, Lewis J. TI Post-ICU syndrome: Rescuing the undiagnosed SO JAAPA-JOURNAL OF THE AMERICAN ACADEMY OF PHYSICIAN ASSISTANTS LA English DT Review DE ICU; critical illness; post-traumatic stress disorder; delirium; postintensive care syndrome; PICS ID INTENSIVE CARE SYNDROME; LONG-TERM-OUTCOMES; CRITICAL ILLNESS; SURVIVORSHIP AB Survivors of critical illness may develop postintensive care syndrome (PICS), a spectrum of conditions that include persistent cognitive dysfunction, acquired weakness, and intrusive memories akin to post-traumatic stress disorder. Relatively few ICU survivors are routinely followed in the outpatient setting by intensivists, but are regularly evaluated by primary care physicians and physician assistants in their practices. Specific and focused education about the key features of PICS, its effect on patients as well as family members, and potential therapeutic interventions may increase recognition of PICS and reduce its effect on survivors of critical illness. C1 [Myers, Elizabeth A.] Medstar Southern Maryland Hosp Ctr, Emergency Med, Clinton, MD USA. [Smith, David A.] Salus Univ, PA Program, Elkins Pk, PA USA. [Smith, David A.] VA Med Ctr, Crit Care Med Surg ICU, Philadelphia, PA USA. [Allen, Steven R.] Penn States Hershey Med Ctr, Hershey, PA USA. [Kaplan, Lewis J.] Philadelphia VA Med Ctr, Surg Crit Care, Philadelphia, PA USA. [Kaplan, Lewis J.] Philadelphia VA Med Ctr, Surg, Philadelphia, PA USA. [Kaplan, Lewis J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Myers, EA (reprint author), Medstar Southern Maryland Hosp Ctr, Emergency Med, Clinton, MD USA. NR 13 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 1547-1896 EI 0893-7400 J9 JAAPA-J AM ACAD PHYS JI JAAPA-J. Am. Acad. Physician Assist. PD APR PY 2016 VL 29 IS 4 BP 34 EP 37 DI 10.1097/01.JAA.0000481401.21841.32 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DO6FZ UT WOS:000377880000014 PM 27023654 ER PT J AU Byers, AL Lai, AX Arean, P Nelson, JC Yaffe, K AF Byers, Amy L. Lai, Amy X. Arean, Patricia Nelson, J. Craig Yaffe, Kristine TI Mental Health Service Use Across the Life Course Among Adults With Psychiatric Disorders and Prior Suicidal Behavior SO PSYCHIATRIC SERVICES LA English DT Article ID PERCEIVED NEED; CARE AB Objective: Little is known about mental health service use by adults with prior suicidal behavior and current mood or anxiety disorders. This study determined nationally representative prevalence estimates of current mental health service use by these adults, examining racial-ethnic, age, and gender differences. Methods: Service use across the life course was examined with Collaborative Psychiatric Epidemiology Survey data from 1,139 adults with a history of suicidal behavior and current mood or anxiety disorders. Results: Overall service use was 47.3%. Across the life course, African Americans showed increasing service use that paralleled use by non-Hispanic whites, Hispanics, and others, whereas use by these three groups decreased in the latter half of the life course (p interaction = .01). Conclusions: Adults with prior suicidal behavior and current mood or anxiety disorders have low mental health service use. Findings of racial-ethnic disparities in use can help identify those in need of care. C1 [Byers, Amy L.; Nelson, J. Craig; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Byers, Amy L.; Lai, Amy X.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Arean, Patricia] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Byers, AL (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.; Byers, AL (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM amy.byers@ucsf.edu FU National Institute on Aging [AG031155]; Avid; [MD007019] FX Dr. Byers is supported by R01 award MD007019, administered by the Northern California Institute for Research and Education, and by resources from the San Francisco Veterans Affairs Medical Center and the National Institutes of Health, National Institute on Minority Health and Health Disparities. Dr. Yaffe is partially supported by K24 midcareer investigator award AG031155 from the National Institute on Aging.; Dr. Nelson reports receiving lecture honoraria from Bristol-Myers Squibb, Genentech, and Otsuka; consulting for Corcept, Lundbeck, and Otsuka; serving on the advisory board for Genentech and Otsuka; receiving research support from Avid; and owning stock in Atossa. Dr. Yaffe reports that she serves on data and safety monitoring boards for Takeda and DIAN. The other authors report no financial relationships with commercial interests. NR 15 TC 0 Z9 0 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2016 VL 67 IS 4 BP 452 EP 455 DI 10.1176/appi.ps.201500019 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DO4TY UT WOS:000377778300019 PM 26766753 ER PT J AU Timko, C Gupta, S Schultz, N Harris, AHS AF Timko, Christine Gupta, Shalini Schultz, Nicole Harris, Alex H. S. TI Veterans' Service Utilization Patterns After Alcohol and Opioid Detoxification in VHA Care SO PSYCHIATRIC SERVICES LA English DT Article ID SUBSTANCE-ABUSE TREATMENT; INPATIENT; OUTCOMES AB Objective: This study aimed to examine detoxification-related service utilization in the Veterans Health Administration (VHA). Methods: VHA data for 266,908 patients were used to examine rates and predictors of receiving detoxification, attending post-detoxification appointments, and entering specialty treatment. Multilevel, mixed-effects logistic regressions were used to examine associations between patient and facility characteristics and service utilization. Results: Nationally, 8.0% of VHA patients with alcohol or opiate dependence received detoxification in fiscal year 2013 (facility range=.1% 220.4%); 43.1% of detoxified patients received follow-up (11.1% 276.4%), and 49.9% entered specialty treatment (13.0%-77.2%). In adjusted analyses, detoxification was more likely among male, younger, white, and homeless patients with documented alcohol or opiate disorders and comorbid general medical conditions but without previous addiction treatment. Detoxification was also more likely in facilities with fewer vacant addiction therapist positions. Follow-up and specialty treatments were more likely among younger, healthier homeless patients with previous addiction treatment and a documented alcohol use disorder. Conclusions: Detoxification-related service utilization was highly variable across the VHA. Interventions are needed to optimize use. C1 [Timko, Christine; Gupta, Shalini; Schultz, Nicole; Harris, Alex H. S.] US Dept Vet Affairs, Hlth Serv Res & Dev, Menlo Pk, CA 94025 USA. RP Timko, C (reprint author), US Dept Vet Affairs, Hlth Serv Res & Dev, Menlo Pk, CA 94025 USA. EM christine.timko@va.gov FU HSR&D Quality Enhancement Research Initiative [RRP 12-525]; HSRD [RCS 00-001, RCS 14-232] FX This work was supported by grant RRP 12-525 from HSR&D Quality Enhancement Research Initiative. Dr. Timko was supported by grant RCS 00-001 and Dr. Harris was supported by grant RCS 14-232, both from HSR&D. NR 17 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2016 VL 67 IS 4 BP 460 EP 464 DI 10.1176/appi.ps.201400579 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DO4TY UT WOS:000377778300021 PM 26766752 ER PT J AU Brennan, L Siderowf, A Rubright, JD Rick, J Dahodwala, N Duda, JE Hurtig, H Stern, M Xie, SX Rennert, L Karlawish, J Shea, JA Trojanowski, JQ Weintraub, D AF Brennan, Laura Siderowf, Andrew Rubright, Jonathan D. Rick, Jacqueline Dahodwala, Nabila Duda, John E. Hurtig, Howard Stern, Matthew Xie, Sharon X. Rennert, Lior Karlawish, Jason Shea, Judy A. Trojanowski, John Q. Weintraub, Daniel TI The Penn Parkinson's Daily Activities Questionnaire-15: Psychometric properties of a brief assessment of cognitive instrumental activities of daily living in Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Instrumental activities of daily living; Cognition ID SOCIETY TASK-FORCE; ALZHEIMERS-DISEASE; IMPAIRMENT; DEMENTIA; AGREEMENT; PATIENT AB Introduction: To describe the psychometric properties of the Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15), a 15-item measure of cognitive instrumental activities of daily living for Parkinson's disease (PD) patients derived from the original 50-item PDAQ. Methods: PDAQ-15 items were chosen by expert consensus. Knowledgeable informants of PD participants (n-= 161) completed the PDAQ-15. Knowledgeable informants were defined as an individual having regular contact with the PD participant. PD participants were assigned a diagnosis of normal cognition, mild cognitive impairment, or dementia based on expert consensus. Results: PDAQ-15 scores correlated strongly with global cognition (Dementia Rating Scale-2, r = 0.71, p < 0.001) and a performance-based functional measure (Direct Assessment of Functional Status, r = 0.83; p < 0.001). PDAQ-15 scores accurately discriminated between non-demented PD participants (normal cognition/mild cognitive impairment) and PD with dementia (ROC curve area = 0.91), participants with and without any cognitive impairment (normal cognition versus mild cognitive impairment/dementia, ROC curve area = 0.85) and between participants with mild cognitive impairment and dementia (ROC curve area = 0.84). Conclusions: The PDAQ-15 shows good discriminant validity across cognitive stages, correlates highly with global cognitive performance, and appears suitable to assess daily cognitive functioning in PD. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Brennan, Laura] Drexel Univ, Coll Med, Drexel Neurosci Inst, 245 N 15th St,7102 NCB, Philadelphia, PA 19102 USA. [Brennan, Laura; Weintraub, Daniel] Univ Penn, Sch Med, Dept Psychiat, 3615 Chestnut St,330, Philadelphia, PA 19104 USA. [Siderowf, Andrew] Avid Radiopharmaceut, 3711 Market St 7, Philadelphia, PA 19104 USA. [Rubright, Jonathan D.] Natl Board Med Examiners, 3750 Market St, Philadelphia, PA 19104 USA. [Rick, Jacqueline; Dahodwala, Nabila; Duda, John E.; Hurtig, Howard; Stern, Matthew; Trojanowski, John Q.; Weintraub, Daniel] Univ Penn, Sch Med, Dept Neurol, 330 S 9th St, Philadelphia, PA 19107 USA. [Duda, John E.; Rennert, Lior; Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. [Xie, Sharon X.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, 8th Floor Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. [Karlawish, Jason] PENN CMU Roybal Ctr Behav Econ & Hlth, LDI Ctr Hlth Incent, Dept Med Eth & Med, 3401 Market St,Suite 320, Philadelphia, PA 19104 USA. [Karlawish, Jason] Alzheimers Dis Ctr, 3401 Market St,Suite 320, Philadelphia, PA 19104 USA. [Shea, Judy A.] Univ Penn, Sch Med, Dept Med, 3400 Civ Ctr Blvd,Bldg 421, Philadelphia, PA 19104 USA. [Rubright, Jonathan D.] Amer Inst Certified Publ Accountants, Durham, NC USA. RP Weintraub, D (reprint author), 3615 Chestnut St,330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU Morris K. Udall Parkinson's Disease Research Center of Excellence grant from NINDS [NS-053488]; Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement [SAP4100027296] FX This study was funded by a Morris K. Udall Parkinson's Disease Research Center of Excellence grant from NINDS (NS-053488) and by SAP4100027296, a health research grant awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001-77. NR 25 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD APR PY 2016 VL 25 BP 21 EP 26 DI 10.1016/j.parkreldis.2016.02.020 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA DK0QD UT WOS:000374616400004 PM 26923524 ER PT J AU Li, HM Hasserjian, RP Kroft, SH Harrington, AM Wheaton, SE Pildain, A Ewalt, MD Gratzinger, D Hosking, P Olteanu, H AF Li, Hongmei Hasserjian, Robert P. Kroft, Steven H. Harrington, Alexandra M. Wheaton, Susan E. Pildain, Alex Ewalt, Mark D. Gratzinger, Dita Hosking, Paul Olteanu, Horatiu TI Pure Erythroid Leukemia and Erythroblastic Sarcoma Evolving From Chronic Myeloid Neoplasms SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Pure erythroid leukemia; Erythroblastic sarcoma; Myeloproliferative neoplasm; Myelodysplastic syndrome ID BONE-MARROW; ERYTHROLEUKEMIA; PRECURSORS; MARKER; ERYTHROPOIESIS; PROGENITORS; GLYCOPHORIN; HEMOGLOBIN; MATURATION; SECTIONS AB Objectives: Pure erythroid leukemia (PEL) is an extremely rare entity that may, even more rarely, evolve from a preexisting chronic myeloid neoplasm (CMN); there is minimal literature regarding this latter phenomenon. Methods: We describe 14 patients with PEL that represented progression from a preexisting myelodysplastic syndrome (MDS, n = 8) or myeloproliferative neoplasm (MPN, n = 6), three of which manifested as erythroblastic sarcoma (EBS), a rare entity. These patients had a highly complex karyotype with prominent clonal evolution and a very aggressive clinical course. Results: Patients with PEL from MDS showed a more rapid progression time to PEL and had lower platelet counts compared with PEL from MPN. No other significant differences were found between the two groups. Conclusions: These data represent the largest cohort of patients with PEL and an antecedent CMN, as well as the largest series of EBS reported to date, and underscore the unique morphologic, cytogenetic, immunophenotypic, and clinical features of this uncommon entity. C1 [Li, Hongmei; Kroft, Steven H.; Harrington, Alexandra M.; Hosking, Paul; Olteanu, Horatiu] Med Coll Wisconsin, Dept Pathol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wheaton, Susan E.] Allina Hlth, Dept Pathol, Minneapolis, MN USA. [Pildain, Alex] Texas Hlth Presbyterian Hosp, Dept Pathol, Dallas, TX USA. [Ewalt, Mark D.; Gratzinger, Dita] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. RP Olteanu, H (reprint author), Med Coll Wisconsin, Dept Pathol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM holteanu@mcw.edu OI Gratzinger, Dita/0000-0002-9182-8123 NR 26 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 2016 VL 145 IS 4 BP 538 EP 551 DI 10.1093/ajcp/aqw033 PG 14 WC Pathology SC Pathology GA DN3FG UT WOS:000376947200012 PM 27124944 ER PT J AU Trikamji, B Thomas, M Hathout, G Mishra, S AF Trikamji, Bhavesh Thomas, Mariam Hathout, Gasser Mishra, Shrikant TI An unusual case of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy with occipital lobe involvement SO ANNALS OF INDIAN ACADEMY OF NEUROLOGY LA English DT Article DE Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); dementia; migraine; magnetic resonance imaging (MRI); occipital lobe; seizures ID CADASIL; PATTERNS AB Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant angiopathy caused by a mutation in the notch 3 gene on chromosome 19. Clinically, patients may be asymptomatic or can present with recurrent ischemic episodes and strokes leading to dementia, depression, pseudobulbar palsy, and hemi-or quadraplegia. Additional manifestations that have been described include migraine (mostly with aura), psychiatric disturbances, and epileptic seizures. Neuroimaging is essential to the diagnosis of CADASIL. On imaging CADASIL is characterized by symmetric involvement by confluent lesions located subcortically in the frontal and temporal lobes as well as in the insula, periventricularly, in the centrum semiovale, in the internal and external capsule, basal ganglia, and brain stem; with relative sparing of the fronto-orbital and the occipital subcortical regions. We describe a 49 year old male with CADASIL with absence of temporal lobe findings on MRI but predominant lesions within the periventricular white matter, occipital lobes with extension into the subcortical frontal lobes, corpus callosum and cerebellar white matter. Although CADASIL characteristically presents with anterior temporal lobe involvement, these findings may be absent and our case addresses the atypical imaging findings in CADASIL. C1 [Trikamji, Bhavesh; Thomas, Mariam; Hathout, Gasser; Mishra, Shrikant] Olive View UCLA Med Ctr, Dept Neurol, 14445 Olive View Dr, Sylmar, CA 91342 USA. [Trikamji, Bhavesh; Hathout, Gasser; Mishra, Shrikant] VA Greater Los Angeles Healthcare Syst, Dept Radiol, Los Angeles, CA USA. [Hathout, Gasser; Mishra, Shrikant] Univ Calif Los Angeles, Los Angeles, CA USA. [Mishra, Shrikant] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Mishra, S (reprint author), 16111 Plummer St, North Hills, CA 91343 USA. EM smishra@usc.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0972-2327 EI 1998-3549 J9 ANN INDIAN ACAD NEUR JI Ann. Indian Acad. Neurol. PD APR-JUN PY 2016 VL 19 IS 2 BP 272 EP 274 DI 10.4103/0972-2327.173403 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA DN0BE UT WOS:000376728600023 PM 27293347 ER PT J AU Jarraya, M Roemer, FW Gale, HI Landreau, P D'Hooghe, P Guermazi, A AF Jarraya, Mohamed Roemer, Frank W. Gale, Heather I. Landreau, Philippe D'Hooghe, Pieter Guermazi, Ali TI MR-arthrography and CT-arthrography in sports-related glenolabral injuries: a matched descriptive illustration SO INSIGHTS INTO IMAGING LA English DT Review DE Magnetic resonance imaging; Multislice computed tomography; Arthrography; Shoulder; Sports injuries ID ANTERIOR SHOULDER INSTABILITY; ROTATOR CUFF INTERVAL; HILL-SACHS LESION; SUPERIOR LABRUM; SLAP LESIONS; ARTHROSCOPY; DIAGNOSIS; VARIANTS; COMPLEX; BICEPS AB The combination of a large range of motion and insufficient bony stabilization makes the glenohumeral joint susceptible to injuries including dislocation in young athletes. Magnetic resonance arthrography (MR-arthrography) and computed tomography arthrography (CT-arthrography) play an important role in the preoperative workup of labroligametous injuries. This paper illustrates MR-arthrography and CT-arthrography findings acquired at the same time on the same subjects to illustrate common causes and sequelae of shoulder instability. Teaching Points . MR-arthrography and CT-arthrography are equivalent for SLAP and full-thickness rotator cuff tears. . CT-arthrography is superior in evaluating osseous defects and cartilage surface lesions. . MR-arthrography is superior in evaluating intrasubstance and extra-articular tendinous injuries. C1 [Jarraya, Mohamed; Roemer, Frank W.; Landreau, Philippe; D'Hooghe, Pieter; Guermazi, Ali] Aspetar Orthopaed & Sports Med Hosp, Doha, Qatar. [Jarraya, Mohamed; Roemer, Frank W.; Guermazi, Ali] Boston Univ, Sch Med, Dept Radiol, 820 Harrison Ave,FGH Bldg,3rd Floor, Boston, MA 02118 USA. [Jarraya, Mohamed] Mercy Catholic Med Ctr, Dept Radiol, Darby, PA USA. [Roemer, Frank W.] Univ Erlangen Nurnberg, Dept Radiol, D-91054 Erlangen, Germany. [Gale, Heather I.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Jarraya, M (reprint author), Aspetar Orthopaed & Sports Med Hosp, Doha, Qatar.; Jarraya, M (reprint author), Boston Univ, Sch Med, Dept Radiol, 820 Harrison Ave,FGH Bldg,3rd Floor, Boston, MA 02118 USA.; Jarraya, M (reprint author), Mercy Catholic Med Ctr, Dept Radiol, Darby, PA USA. EM mohamedjarraya@gmail.com NR 26 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1869-4101 J9 INSIGHTS IMAGING JI Insights Imaging PD APR PY 2016 VL 7 IS 2 BP 167 EP 177 DI 10.1007/s13244-015-0462-5 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DN4GV UT WOS:000377022900001 PM 26746976 ER PT J AU Malouf, J Langdahl, B Libanati, C Crittenden, DB Bolognese, MA Brown, JP Daizadeh, NS Dokoupilova, E Engelke, K Finkelstein, JS Genant, HK Goemaere, S Hyldstrup, L Jodar-Gimeno, E Keaveny, TM Kendler, D Lakatos, P Maddox, J Massari, FE Molina, JF Ulla, MR Grauer, A AF Malouf, J. Langdahl, B. Libanati, C. Crittenden, D. B. Bolognese, M. A. Brown, J. P. Daizadeh, N. S. Dokoupilova, E. Engelke, K. Finkelstein, J. S. Genant, H. K. Goemaere, S. Hyldstrup, L. Jodar-Gimeno, E. Keaveny, T. M. Kendler, D. Lakatos, P. Maddox, J. Massari, F. E. Molina, J. F. Ulla, M. R. Grauer, A. TI SUPERIOR GAINS IN BONE MINERAL DENSITY AND ESTIMATED STRENGTH AT THE HIP FOR ROMOSOZUMAB COMPARED WITH TERIPARATIDE IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS TRANSITIONING FROM BISPHOSPHONATE THERAPY: RESULTS OF THE PHASE 3 OPEN-LABEL STRUCTURE STUDY SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases CY APR 14-17, 2016 CL Malaga, SPAIN SP WCO, IOF, ESCEO C1 [Malouf, J.] Univ Autonoma Barcelona, E-08193 Barcelona, Spain. [Langdahl, B.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Libanati, C.] UCB Pharma, Brussels, Belgium. [Crittenden, D. B.; Daizadeh, N. S.; Maddox, J.; Grauer, A.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Bolognese, M. A.] Bethesda Hlth Res Ctr, Bethesda, MD USA. [Brown, J. P.] Univ Laval, Quebec City, PQ, Canada. [Brown, J. P.] CHU Quebec CHUL Res Ctr, Quebec City, PQ, Canada. [Dokoupilova, E.] Med Plus, Uherske Hradiste, Czech Republic. [Engelke, K.] BioClinica Inc, Hamburg, Germany. [Finkelstein, J. S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Genant, H. K.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Goemaere, S.] Ghent Univ Hosp, Ghent, Belgium. [Hyldstrup, L.] Hvidovre Univ Hosp, DK-2650 Hvidovre, Denmark. [Jodar-Gimeno, E.] Hosp Univ Quiron, Serv Endocrinol, Madrid, Spain. [Keaveny, T. M.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Kendler, D.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Lakatos, P.] Semmelweis Univ, Dept Med, H-1085 Budapest, Hungary. [Massari, F. E.] Inst Invest Metab, Buenos Aires, DF, Argentina. [Molina, J. F.] Reumalab Ctr Integral Reumatol, Medellin, Colombia. [Ulla, M. R.] Inst Latinoamer Invest Med, Cordoba, Argentina. NR 0 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2016 VL 27 SU 1 MA OC3 BP S40 EP S41 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DM6NH UT WOS:000376469100014 ER PT J AU Wojciechowski, D Chandran, S AF Wojciechowski, David Chandran, Sindhu TI BK Virus Infection After Kidney Transplantation: The Data Are Mounting for a Personalized Approach SO TRANSPLANTATION LA English DT Editorial Material ID DONOR; RECIPIENTS; VIREMIA; ORIGIN; RISK C1 [Wojciechowski, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA. [Wojciechowski, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA USA. [Chandran, Sindhu] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. RP Wojciechowski, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM DWOJCIECHOWSKI@mgh.harvard.edu NR 11 TC 1 Z9 1 U1 1 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 APR PY 2016 VL 100 IS 4 BP 703 EP 704 DI 10.1097/TP.0000000000001067 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DN5QR UT WOS:000377125700009 PM 26760573 ER PT J AU Parajuli, S Lockridge, JB Langewisch, ED Norman, DJ Kujovich, JL AF Parajuli, Sandesh Lockridge, Joseph B. Langewisch, Eric D. Norman, Douglas J. Kujovich, Jody L. TI Hypercoagulability in Kidney Transplant Recipients SO TRANSPLANTATION LA English DT Review ID FACTOR-V-LEIDEN; RENAL GRAFT THROMBOSIS; ANTIPHOSPHOLIPID ANTIBODY SYNDROME; MOLECULAR-WEIGHT HEPARIN; PROTEIN-S DEFICIENCY; ALLOGRAFT THROMBOSIS; RISK-FACTORS; SINGLE-CENTER; VASCULAR COMPLICATIONS; SURGICAL COMPLICATIONS AB Thrombosis remains an important complication after kidney transplantation. Outcomes for graft and deep vein thrombosis are not favorable. The majority of early kidney transplant failure in adults is due to allograft thrombosis. Risk stratification, early diagnosis, and appropriate intervention are critical to the management of thrombotic complications of transplant. In patients with end-stage renal disease, the prevalence of acquired risk factors for thrombosis is significantly high. Because of hereditary and acquired risk factors, renal transplant recipients manifest features of a chronic prothrombotic state. Identification of hereditary thrombotic risk factors before transplantation may be a useful tool for selecting appropriate candidates for thrombosis prophylaxis immediately after transplantation. Short-term anticoagulation may be appropriate for all patients after kidney transplantation. C1 [Parajuli, Sandesh] Univ Wisconsin, Sch Med & Publ Hlth, Univ Wisconsin Hosp & Clin, Div Nephrol,Dept Med, Madison, WI USA. [Parajuli, Sandesh; Lockridge, Joseph B.; Langewisch, Eric D.; Norman, Douglas J.] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol, 2611 SW 3rd Ave,Ste 360, Portland, OR 97201 USA. [Lockridge, Joseph B.; Langewisch, Eric D.; Norman, Douglas J.] Portland VA Med Ctr, Portland, OR USA. [Kujovich, Jody L.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. RP Norman, DJ (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Nephrol, 2611 SW 3rd Ave,Ste 360, Portland, OR 97201 USA. EM normand@ohsu.edu NR 100 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD APR PY 2016 VL 100 IS 4 BP 719 EP 726 DI 10.1097/TP.0000000000000887 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DN5QR UT WOS:000377125700015 PM 26413991 ER PT J AU Dohlman, TH Di Zazzo, A Omoto, M Hua, J Ding, J Hamrah, P Chauhan, SK Dana, R AF Dohlman, Thomas H. Di Zazzo, Antonio Omoto, Masahiro Hua, Jing Ding, Julia Hamrah, Pedram Chauhan, Sunil K. Dana, Reza TI E-Selectin Mediates Immune Cell Trafficking in Corneal Transplantation SO TRANSPLANTATION LA English DT Article ID GLYCOPROTEIN LIGAND-1 PSGL-1; ADHESION MOLECULE EXPRESSION; TOLEROGENIC DENDRITIC CELLS; NECROSIS-FACTOR-ALPHA; CD8(+) T-CELLS; P-SELECTIN; LYMPHATIC ENDOTHELIUM; ALLOGRAFT-REJECTION; IMPROVED OUTCOMES; T-HELPER-2 CELLS AB Background. Immune rejection continues to threaten all tissue transplants. Here we sought to determine whether platelet (P)and endothelial (E)-selectin mediate T cell recruitment in corneal transplantation and whether their blockade can reduce T cell graft infiltration and improve long-term corneal allograft survival. Methods. In a murine model of allogeneic corneal transplantation, we used PCR and immunohistochemistry to investigate expression of P-and E-selectin in rejected versus accepted allografts and lymph node flow cytometry to assess expression of selectin ligands by effector T cells. Using P-and E-selectin neutralizing antibodies, we evaluated the effect of blockade on CD4 T cell recruitment, as well as the effect of anti-E-selectin on long-term allograft survival. Results. The P-(93.3-fold, P < 0.05) and E-selectin (17.1-fold, P < 0.005) are upregulated in rejected versus accepted allogeneic transplants. Type 1 T helper cells from hosts with accepted and rejected grafts express high levels of P-selectin glycoprotein ligand 1 and glycosylated CD43. In vivo blockade of P (0.47 +/- 0.03, P < 0.05) and E selectin (0.49 +/- 0.1, P < 0.05) reduced the number of recruited T cells compared with IgG control (0.98 +/- 0.1). Anti-E-selectin reduced the number of mature antigen-presenting cells trafficking to lymphoid tissue compared with control (6.96 +/- 0.9 vs 12.67 +/- 0.5, P < 0.05). Anti-E-selectin treatment delayed graft rejection and increased survival compared with control, although this difference did not reach statistical significance. Conclusions. In a model of corneal transplantation, P-and E-selectin mediate T cell recruitment to the graft, E-selectin mediates APC trafficking to lymphoid tissue, and blockade of E-selectin has a modest effect on improving long-term graft survival. C1 [Dohlman, Thomas H.; Di Zazzo, Antonio; Omoto, Masahiro; Hua, Jing; Ding, Julia; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Hamrah, Pedram] Tufts Univ, Sch Med, Tufts Med Ctr, Cornea Serv,New England Eye Ctr,Dept Ophthalmol, Boston, MA 02111 USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU National Institutes of Health/National Eye Institute [NIH R01 EY012963, NIH K08 EY020575]; Eye Bank Association of America/Richard Lindstrom Grant FX This study was supported in part by the National Institutes of Health/National Eye Institute NIH R01 EY012963 (RD), NIH K08 EY020575 (PH), Eye Bank Association of America/Richard Lindstrom Grant (THD). NR 60 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD APR PY 2016 VL 100 IS 4 BP 772 EP 780 DI 10.1097/TP.0000000000001107 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DN5QR UT WOS:000377125700021 PM 26910325 ER PT J AU Lockhart, SR Fothergill, AW Iqbal, N Bolden, CB Grossman, NT Garvey, EP Brand, SR Hoekstra, WJ Schotzinger, RJ Ottinger, E Patterson, TF Wiederhold, NP AF Lockhart, Shawn R. Fothergill, Annette W. Iqbal, Naureen Bolden, Carol B. Grossman, Nina T. Garvey, Edward P. Brand, Stephen R. Hoekstra, William J. Schotzinger, Robert J. Ottinger, Elizabeth Patterson, Thomas F. Wiederhold, Nathan P. TI The Investigational Fungal Cyp51 Inhibitor VT-1129 Demonstrates Potent In Vitro Activity against Cryptococcus neoformans and Cryptococcus gattii SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIFUNGAL SUSCEPTIBILITIES AB The in vitro activities of the novel fungal Cyp51 inhibitor VT-1129 were evaluated against a large panel of Cryptococcus neoformans and Cryptococcus gattii isolates. VT-1129 demonstrated potent activities against both Cryptococcus species as demonstrated by low MIC50 and MIC90 values. For C. gattii, the in vitro potency was maintained against all genotypes. In addition, significantly lower geometric mean MICs were observed for VT-1129 than for fluconazole against C. neoformans, including isolates with reduced fluconazole susceptibility. C1 [Lockhart, Shawn R.; Iqbal, Naureen; Bolden, Carol B.; Grossman, Nina T.] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA. [Fothergill, Annette W.; Patterson, Thomas F.; Wiederhold, Nathan P.] Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA. [Garvey, Edward P.; Brand, Stephen R.; Hoekstra, William J.; Schotzinger, Robert J.] Viamet Pharmaceut Inc, Durham, NC USA. [Ottinger, Elizabeth] NIH, Therapeut Rare & Neglected Dis Bethesda, Bldg 10, Bethesda, MD 20892 USA. [Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Wiederhold, NP (reprint author), Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA. EM wiederholdn@uthscsa.edu FU National Institutes of Health National Institute of Allergy and Infectious Diseases [N01-AI-25475]; National Institutes of Health, National Center for Advancing Translational Sciences, Therapeutics for Rare and Neglected Diseases (TRND) Program; Viamet Pharmaceuticals, Inc. FX This project was funded by the National Institutes of Health National Institute of Allergy and Infectious Diseases under contract no. N01-AI-25475 (Thomas F. Patterson), the National Institutes of Health, National Center for Advancing Translational Sciences, Therapeutics for Rare and Neglected Diseases (TRND) Program (Shawn R. Lockhart), and Viamet Pharmaceuticals, Inc. (Nathan P. Wiederhold). VT-1129 powder was provided by Viamet Pharmaceuticals, Inc. NR 18 TC 2 Z9 2 U1 2 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 APR PY 2016 VL 60 IS 4 BP 2528 EP 2531 DI 10.1128/AAC.02770-15 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DM6XL UT WOS:000376496100072 PM 26787697 ER PT J AU Razzaque, MS Atfi, A AF Razzaque, Mohammed S. Atfi, Azeddine TI TGIF function in oncogenic Wnt signaling SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE TGIF; Axin1; Axin2; beta-Catenin; Mammary tumor ID BETA-CATENIN; INTERACTING-FACTOR; NEGATIVE REGULATOR; MOUSE DEVELOPMENT; BREAST-CANCER; TGF-BETA; AXIN; APC; ACTIVATION; MUTATIONS AB Transforming growth-interacting factor (TGIF) has been implicated in the pathogenesis of many types of human cancer, but the underlying mechanisms remained mostly enigmatic. Our recent study has revealed that TGIF functions as a mediator of oncogenic Wnt/beta-catenin signaling. We found that TGIF can interact with and sequesters Axin1 and Axin2 into the nucleus, thereby culminating in disassembly of the beta-catenin-destruction complex and attendant accumulation of beta-catenin in the nucleus, where it activates expression of Wnt target genes, including TGIF itself. We have provided proof-of-concept evidences that high levels of TGIF expression correlate with poor prognosis in patients with triple negative breast cancer (TNBC), and that TGIF empowers Wnt-driven mammary tumorigenesis in vivo. Here, we will briefly summarize how TGIF influences Wnt signaling to promote tumorigenesis. (C) 2015 Elsevier B.V. All rights reserved. C1 [Razzaque, Mohammed S.] Harvard Univ, Sch Dent Med Affiliate, Forsyth Inst, Dept Appl Oral Sci, 245 First St, Cambridge, MA 02142 USA. [Razzaque, Mohammed S.] Saba Univ, Sch Med, Dept Pathol, Church St, Saba, Dutch Caribbean, Netherlands. [Atfi, Azeddine] Univ Mississippi, Med Ctr, Inst Canc, 2500 North State St, Jackson, MS 39216 USA. [Atfi, Azeddine] Univ Mississippi, Med Ctr, Dept Biochem, 2500 North State St, Jackson, MS 39216 USA. [Atfi, Azeddine] Hop St Antoine, INSERM UMRS 938, Lab Cell Signaling & Carcinogenesis, 34 Rue Crozatier, F-75012 Paris, France. RP Razzaque, MS (reprint author), Forsyth Inst, Dept Appl Oral Sci, 245 First St, Cambridge, MA 02142 USA. EM mrazzaque@forsyth.org FU Association pour la Recherche sur le Cancer; CNRS; INSERM; NIH [1R01AR059070] FX This work is supported in part by grants from Association pour la Recherche sur le Cancer, CNRS, INSERM, and NIH (1R01AR059070) to A.A. NR 40 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X EI 0006-3002 J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD APR PY 2016 VL 1865 IS 2 BP 101 EP 104 DI 10.1016/j.bbcan.2015.10.003 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA DM7NB UT WOS:000376546200001 PM 26522669 ER PT J AU Yung, M Iafe, N Sarraf, D AF Yung, Madeline Iafe, Nicholas Sarraf, David TI Optical coherence tomography angiography of a retinal astrocytic hamartoma SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Letter C1 [Yung, Madeline; Iafe, Nicholas; Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA.; Sarraf, D (reprint author), Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. EM dsarraf@ucla.edu NR 6 TC 0 Z9 0 U1 1 U2 1 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 EI 1715-3360 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD APR PY 2016 VL 51 IS 2 BP E62 EP E64 DI 10.1016/j.jcjo.2015.11.005 PG 4 WC Ophthalmology SC Ophthalmology GA DM7BR UT WOS:000376508400010 PM 27085280 ER PT J AU Sakai, S Anada, T Tsuchiya, K Yamazaki, H Margolis, HC Suzuki, O AF Sakai, Susumu Anada, Takahisa Tsuchiya, Kaori Yamazaki, Hajime Margolis, Henry C. Suzuki, Osamu TI Comparative study on the resorbability and dissolution behavior of octacalcium phosphate, beta-tricalcium phosphate, and hydroxyapatite under physiological conditions SO DENTAL MATERIALS JOURNAL LA English DT Article DE Resorbability; Dissolution; Octacalcium phosphate; beta-tricalcium phosphate; Hydroxyapatite ID CALCIUM-PHOSPHATE; BONE-FORMATION; CARBONATE-APATITE; PORCINE AMELOGENESIS; CRYSTAL-CHEMISTRY; IN-VITRO; SOLUBILITY; BIOMATERIALS; IMPLANTATION; MECHANISM AB The dissolution behaviors of octacalcium phosphate (OCP), beta-tricalcium phosphate (beta-TCP), and hydroxyapatite (HA) were compared by implanting the materials in rat subcutaneous pouches for 8 weeks using a filter chamber or immersing them in simulated body fluid (SBF) or Tris-HCl buffer for 2 weeks at pH 7.4 and 37 degrees C. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and chemical analysis were conducted on these materials. Degree of supersaturation (DS) in the two solutions immersed with each calcium phosphate material was calculated from their chemical compositions. The results showed that OCP partially converted to apatitic crystals, while beta-TCP and HA remained unchanged after the implantation. The DS of the SBF solution remained slightly supersaturated with respect to OCP and beta-TCP, but slightly undersaturated in the Tris-HCl buffer. These findings suggest that previously reported OCP and beta-TCP biodegradation could be induced through cell-mediated osteoclastic resorption rather than a simple dissolution process. C1 [Sakai, Susumu; Anada, Takahisa; Tsuchiya, Kaori; Suzuki, Osamu] Tohoku Univ, Grad Sch Dent, Div Craniofacial Funct Engn, Sendai, Miyagi 9808575, Japan. [Yamazaki, Hajime; Margolis, Henry C.] Forsyth Inst, Dept Appl Oral Sci, Ctr Biomineralizat, Cambridge, MA 02142 USA. RP Suzuki, O (reprint author), Tohoku Univ, Grad Sch Dent, Div Craniofacial Funct Engn, Sendai, Miyagi 9808575, Japan. EM suzuki-o@m.tohoku.ac.jp FU Ministry of Education, Science, Sports, and Culture of Japan [23106010, 23390450, 25670829] FX This study was supported by Grants-in Aid (23106010, 23390450 and 25670829) from the Ministry of Education, Science, Sports, and Culture of Japan. NR 60 TC 2 Z9 2 U1 9 U2 18 PU JAPANESE SOC DENTAL MATERIALS DEVICES PI TOKYO PA C/O KOKU HOKEN KYOKAI, 1-43-9 KOMAGOME TS BDG, KOMAGOME, TOSHIMA-KU, TOKYO, 170-0003, JAPAN SN 0287-4547 J9 DENT MATER J JI Dent. Mater. J. PD APR PY 2016 VL 35 IS 2 BP 216 EP 224 DI 10.4012/dmj.2015-255 PG 9 WC Dentistry, Oral Surgery & Medicine; Materials Science, Biomaterials SC Dentistry, Oral Surgery & Medicine; Materials Science GA DM3CS UT WOS:000376225000009 PM 27041011 ER PT J AU Hainline, B Drezner, J Baggish, A Harmon, KG Emery, MS Myerburg, RJ Sanchez, E Molossi, S Parsons, JT Thompson, PD AF Hainline, Brian Drezner, Jonathan Baggish, Aaron Harmon, Kimberly G. Emery, Michael S. Myerburg, Robert J. Sanchez, Eduardo Molossi, Silvana Parsons, John T. Thompson, Paul D. TI Interassociation Consensus Statement on Cardiovascular Care of College Student-Athletes SO JOURNAL OF ATHLETIC TRAINING LA English DT Article DE cardiac arrest; electrocardiogram; emergency action plan; pre-participation screening; student-athlete; sudden cardiac death ID AMERICAN-HEART-ASSOCIATION; SUDDEN CARDIAC-ARREST; AUTOMATED EXTERNAL DEFIBRILLATORS; OF-CARDIOLOGY-FOUNDATION; SCIENTIFIC STATEMENT; DISQUALIFICATION RECOMMENDATIONS; HIGH-SCHOOL; CARDIOPULMONARY-RESUSCITATION; CLINICAL CARDIOLOGY; SEATTLE CRITERIA AB Cardiovascular evaluation and care of college student-athletes is gaining increasing attention from both the public and medical communities. Emerging strategies include screening of the general athlete population, recommendations of permissible levels of participation by athletes with identified cardiovascular conditions, and preparation for responding to unanticipated cardiac events in athletic venues. The primary focus has been sudden cardiac death and the utility of screening with or without advanced cardiac screening. The National Collegiate Athletic Association convened a multidisciplinary task force to address cardiovascular concerns in collegiate student-athletes and to develop consensus for an interassociation statement. This document summarizes the task force deliberations and follow-up discussions, and includes available evidence on cardiovascular risk, pre-participation evaluation, and the recognition of and response to cardiac arrest. Future recommendations for cardiac research initiatives, education, and collaboration are also provided. (C) 2016 by the American College of Cardiology Foundation. C1 [Hainline, Brian; Parsons, John T.] Natl Collegiate Athlet Assoc, Sport Sci Inst, POB 6222, Indianapolis, IN 46206 USA. [Drezner, Jonathan; Harmon, Kimberly G.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Baggish, Aaron] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. [Emery, Michael S.] Indiana Univ Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. [Myerburg, Robert J.] Univ Miami, Miller Sch Med, Div Cardiol, Miami, FL 33136 USA. [Sanchez, Eduardo] Amer Heart Assoc, Dallas, TX USA. [Molossi, Silvana] Baylor Coll Med, Dept Pediat, Div Pediat Cardiol, Houston, TX 77030 USA. [Thompson, Paul D.] Hartford Hosp, Div Cardiol, Hartford, CT 06115 USA. RP Hainline, B (reprint author), Natl Collegiate Athlet Assoc, Sport Sci Inst, POB 6222, Indianapolis, IN 46206 USA. EM bhainline@ncaa.org FU NCAA Sport Science Institute; Genomas; Roche; Sanofi; Regeneron; Esperion; Amarin; Pfizer FX Funding for the multidisciplinary task force, held at the National Collegiate Athletic Association (NCAA) headquarters in September 2014, was provided by the NCAA Sport Science Institute. The task force included representatives from the following affiliations: American Academy of Pediatrics' Council on Sports Medicine and Physical Fitness; National Athletic Trainers' Association; College Athletic Trainers' Society; American Medical Society for Sports Medicine; American College of Cardiology Sports and Exercise Cardiology Leadership Council; National Federation of State High School Associations; American Orthopaedic Society for Sports Medicine; NCAA Student-Athlete Advisory Council; American Osteopathic Academy of Sports Medicine, National Strength and Conditioning Association; Collegiate Strength and Conditioning Coaches Association; American Heart Association; NCAA Committee on Competitive Safeguards and Medical Aspects of Sports; and the American College of Sports Medicine. Dr. Thompson has received research support from Genomas, Roche, Sanofi, Regeneron, Esperion, Amarin, and Pfizer; has served as a consultant for Amgen, Regeneron, Merck, Esperion, and Sanofi; has received speaker honoraria from Merck, AstraZeneca, Regeneron, Sanofi, and Amgen; owns stock in AbbVie, Abbott Labs, CVS, General Electric, Johnson & Johnson, Medtronic, and JA Willey; and has provided expert legal testimony on exercise-related cardiac events and statin myopathy. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 76 TC 2 Z9 2 U1 2 U2 3 PU NATL ATHLETIC TRAINERS ASSOC INC PI DALLAS PA 2952 STEMMONS FREEWAY, DALLAS, TX 75247 USA SN 1062-6050 EI 1938-162X J9 J ATHL TRAINING JI J. Athl. Train. PD APR PY 2016 VL 51 IS 4 BP 344 EP 357 DI 10.4085/j.jacc.2016.03.527 PG 14 WC Sport Sciences SC Sport Sciences GA DM6DQ UT WOS:000376441000010 PM 27111694 ER PT J AU Lee, CT Vo, TT Cohen, AS Ahmed, S Zhang, Y Mao, JR Chen, L AF Lee, Cheng-ting Vo, Trang T. Cohen, Abigail S. Ahmed, Shihab Zhang, Yi Mao, Jianren Chen, Lucy TI Profiles of Urine Drug Test in Clinical Pain Patients vs Pain Research Study Subjects SO PAIN MEDICINE LA English DT Article DE Urine Drug Test; Urine Drug Screening; Opioid; Illicit Drug; Clinical Study; Clinical Trial; Pain; Pain Management; Opioid Therapy ID OPIOID THERAPY; MANAGEMENT; RECOMMENDATIONS; POPULATION; ADHERENCE AB Objective. To examine similarities and differences in urine drug test (UDT) results in clinical pain patients and pain subjects participating in pain research studies. Design. An observational study with retrospective chart review and data analysis. Methods. We analyzed 1,874 UDT results obtained from 1) clinical pain patients (Clinical Group; n = 1,529) and 2) pain subjects consented to participate in pain research studies (Research Group; n = 345). Since several medications such as opioids used in pain management are drugs of abuse (DOA) and can result in a positive UDT, we specifically identified those cases of positive UDT due to nonprescribed DOA and designated these cases as positive UDT with DOA (PUD). Results. We found that 1) there was a higher rate of PUD in clinical pain patients (41.3%) than in pain research study subjects (14.8%); 2) although subjects in the Research Group were informed ahead of time that UDT will be conducted as a screening test, a substantial number (14.8%) of pain research study subjects still showed PUD; 3) there were different types of DOA between clinical pain patients (cannabinoids as the top DOA) and research study subjects (cocaine as the top DOA); and 4) a common factor associated with PUD was opioid therapy in both Clinical Group and Research Group. Conclusion. These results support previous findings that PUD is a common finding in clinical pain patients, particularly in those prescribed opioid therapy, and we suggest that UDT be used as routine screening testing in pain research studies. C1 [Lee, Cheng-ting] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Vo, Trang T.; Cohen, Abigail S.; Ahmed, Shihab; Zhang, Yi; Mao, Jianren; Chen, Lucy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. RP Chen, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia,MGH Ctr Translat Pain Res Crit Ca, Boston, MA 02114 USA. EM llchen@partners.org FU NIH [DA022576, DA036564]; Foundation for Anesthesia Education and Research FX This work was supported by NIH R01 grants DA022576 and DA036564 and the Foundation for Anesthesia Education and Research. NR 23 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD APR PY 2016 VL 17 IS 4 BP 636 EP 643 DI 10.1111/pme.12900 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DM5JB UT WOS:000376383400004 PM 26398237 ER PT J AU Bornigen, D Tyekucheva, S Wang, XD Rider, JR Lee, GS Mucci, LA Sweeney, C Huttenhower, C AF Boernigen, Daniela Tyekucheva, Svitlana Wang, Xiaodong Rider, Jennifer R. Lee, Gwo-Shu Mucci, Lorelei A. Sweeney, Christopher Huttenhower, Curtis TI Computational Reconstruction of NF kappa B Pathway Interaction Mechanisms during Prostate Cancer SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID GENE-EXPRESSION; INTERACTION DATABASE; FUNCTIONAL GENOMICS; RECEPTOR ACTIVATOR; AUTOIMMUNE-DISEASE; MOLECULAR PATHWAYS; CANDIDATE GENES; CELL-LINE; TNF-ALPHA; IN-VITRO AB Molecular research in cancer is one of the largest areas of bioinformatic investigation, but it remains a challenge to understand biomolecular mechanisms in cancer-related pathways from high-throughput genomic data. This includes the Nuclear-factor-kappa-B (NF kappa B) pathway, which is central to the inflammatory response and cell proliferation in prostate cancer development and progression. Despite close scrutiny and a deep understanding of many of its members' biomolecular activities, the current list of pathway members and a systems-level understanding of their interactions remains incomplete. Here, we provide the first steps toward computational reconstruction of interaction mechanisms of the NF kappa B pathway in prostate cancer. We identified novel roles for ATF3, CXCL2, DUSP5, JUNB, NEDD9, SELE, TRIB1, and ZFP36 in this pathway, in addition to new mechanistic interactions between these genes and 10 known NF kappa B pathway members. A newly predicted interaction between NEDD9 and ZFP36 in particular was validated by co-immunoprecipitation, as was NEDD9' s potential biological role in prostate cancer cell growth regulation. We combined 651 gene expression datasets with 1.4M gene product interactions to predict the inclusion of 40 additional genes in the pathway. Molecular mechanisms of interaction among pathway members were inferred using recent advances in Bayesian data integration to simultaneously provide information specific to biological contexts and individual biomolecular activities, resulting in a total of 112 interactions in the fully reconstructed NF kappa B pathway: 13 (11%) previously known, 29 (26%) supported by existing literature, and 70 (63%) novel. This method is generalizable to other tissue types, cancers, and organisms, and this new information about the NF kappa B pathway will allow us to further understand prostate cancer and to develop more effective prevention and treatment strategies. C1 [Boernigen, Daniela; Huttenhower, Curtis] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Boernigen, Daniela; Huttenhower, Curtis] Broad Inst MIT & Harvard, Cambridge, MA USA. [Tyekucheva, Svitlana] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Wang, Xiaodong; Lee, Gwo-Shu; Sweeney, Christopher] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Rider, Jennifer R.; Mucci, Lorelei A.] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Boernigen, Daniela] Univ Heart Ctr Hamburg Eppendorf, Clin Gen & Intervent Cardiol, Hamburg, Germany. [Boernigen, Daniela] Hamburg Lubeck Kiel Partner Site, German Ctr Cardiovasc Res DZHK, Hamburg, Germany. RP Huttenhower, C (reprint author), Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.; Huttenhower, C (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM chuttenh@hsph.harvard.edu FU NSF [DBI-1053486]; NIH [R01CA151993]; DoD [W81XWH-11-1-0379] FX NSF DBI-1053486, NIH R01CA151993 (PI Shuji Ogino), DoD W81XWH-11-1-0379 (PI CS) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 131 TC 0 Z9 1 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2016 VL 12 IS 4 AR e1004820 DI 10.1371/journal.pcbi.1004820 PG 30 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA DM8BA UT WOS:000376584400001 PM 27078000 ER PT J AU Mao, HQ Driscoll, SJ Li, JS Li, GA Wood, KB Cha, TD AF Mao, Haiqing Driscoll, Sean J. Li, Jing-Sheng Li, Guoan Wood, Kirkham B. Cha, Thomas D. TI Dimensional changes of the neuroforamina in subaxial cervical spine during in vivo dynamic flexion-extension SO SPINE JOURNAL LA English DT Article DE Cervical spine; Dynamic cervical motion; Fluoroscopy; Kinematics; Neuroforaminal area; Neuroforaminal dimension ID NERVE ROOT COMPRESSION; AXIAL ROTATION; FORAMEN; MOTION; RADIOGRAPHS; VALIDATION; KINEMATICS; DISC AB BACKGROUND CONTEXT: Neuroforaminal stenosis is one of the key factors causing clinical symptoms in patients with cervical radiculopathy. Previous quantitative studies on the neuroforaminal dimensions have focused on measurements in a static position. Little is known about dimensional changes of the neuroforamina in the cervical spine during functional dynamic neck motion under physiological loading conditions. PURPOSE: This study aimed to investigate the in vivo dimensional changes of the neuroforamina in human cervical spine (C3-C7) during dynamic flexion-extension neck motion. STUDY DESIGN: A case-control study was carried out. METHODS: Ten asymptomatic subjects were recruited for this study. The cervical spine of each subject underwent magnetic resonance image scanning for construction of three-dimensional (3-D) vertebrae models from C3 to C7. The cervical spine was then imaged using a dual fluoroscopic system while the subject performed a dynamic flexion-extension neck motion in a sitting position. The 3-D vertebral models and the fluoroscopic images were used to reproduce the in vivo vertebral motion. The dimensions (area, height, and width) were measured for each cervical neuroforamen (C3/C4, C4/C5, C5/C6, and C6/C7) in the following functional positions: neutral position, maximal flexion, and maximal extension. Repeated measures analysis of variance and post hoc analysis were used to examine the differences between levels and positions. RESULTS: Compared with the neutral position, almost all dimensional parameters (area, height, and width) of the subaxial cervical neuroforamina decreased in extension and increased in flexion, except the neuroforaminal area at C5/C6 (p=. 07), and the neuroforaminal height at C6/C7 (p=. 05) remained relatively constant from neutral to extension. When comparisons of the overall change from extension to flexion were made between segments, the overall changes of the neuroforaminal area and height revealed no significant differences between segments, and the width overall change of the upper levels (C3/C4 and C4/C5) was significantly greater than the lower levels (C5/C6 and C6/C7) (p<. 01). CONCLUSIONS: The dimensional changes of the cervical neuroforamina showed segment-dependent characteristics during the dynamic flexion-extension. These data may have implications for diagnosis and treatment of patients with cervical radiculopathy. (C) 2015 Elsevier Inc. All rights reserved. C1 [Mao, Haiqing; Driscoll, Sean J.; Li, Jing-Sheng; Li, Guoan; Wood, Kirkham B.; Cha, Thomas D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St GRJ 1215, Boston, MA 02114 USA. [Mao, Haiqing] Soochow Univ, Affiliated Hosp 1, Dept Orthopaed Surg, 188 Shizi Rd, Suzhou 215006, Jiangsu, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthoped Bioengn Lab, 55 Fruit St GRJ 1215, Boston, MA 02114 USA. EM GLI1@mgh.harvard.edu FU National Institutes of Health [R21AR057989]; K2M Group Holdings, Inc; Jiangsu Government Scholarship for Overseas Studies [JS-2012-117] FX The authors would like to gratefully acknowledge financial support from the National Institutes of Health (R21AR057989), K2M Group Holdings, Inc, and Jiangsu Government Scholarship for Overseas Studies (JS-2012-117). NR 21 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD APR PY 2016 VL 16 IS 4 BP 540 EP 546 DI 10.1016/j.spinee.2015.11.052 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DM6GG UT WOS:000376448000039 PM 26681352 ER PT J AU Spector, M AF Spector, Myron TI Decellularized tissues and organs: an historical perspective and prospects for the future SO BIOMEDICAL MATERIALS LA English DT Editorial Material ID INTESTINAL SUBMUCOSA; ADIPOSE-TISSUE; SMALL BOWEL; REPLACEMENT; SUBSTITUTE; PLATFORM; MATRIX; VEINS; MODEL; BONE C1 [Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. RP Spector, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. EM mspector@bwh.harvard.edu NR 26 TC 0 Z9 0 U1 3 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 EI 1748-605X J9 BIOMED MATER JI Biomed. Mater. PD APR PY 2016 VL 11 IS 2 AR 020201 DI 10.1088/1748-6041/11/2/020201 PG 3 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA DL3GY UT WOS:000375523400001 ER PT J AU Krzystyniak, J Ceppi, L Dizon, DS Birrer, MJ AF Krzystyniak, J. Ceppi, L. Dizon, D. S. Birrer, M. J. TI Epithelial ovarian cancer: the molecular genetics of epithelial ovarian cancer SO ANNALS OF ONCOLOGY LA English DT Article DE ovarian cancer; genomics; biomarkers; clinical trials ID GRADE SEROUS CARCINOMA; MALIGNANT POTENTIAL TUMORS; GYNECOLOGIC-ONCOLOGY-GROUP; CLEAR-CELL CARCINOMA; ADVANCED-STAGE; EXPRESSION PROFILES; TP53 MUTATIONS; SURVIVAL; PERITONEUM; CHEMOTHERAPY AB Background: Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide, despite gains in diagnostics and treatments made over the last three decades. Existing markers of ovarian cancer possess very limited clinical relevance highlighting the emerging need for identification of novel prognostic biomarkers as well as better predictive factors that might allow the stratification of patients who could benefit from a more targeted approach. Patients and methods: A summary of molecular genetics of EOC. Results: Large-scale high-throughput genomic technologies appear to be powerful tools for investigations into the genetic abnormalities in ovarian tumors, including studies on dysregulated genes and aberrantly activated signaling pathways. Such technologies can complement well-established clinical histopathology analysis and tumor grading and will hope to result in better, more tailored treatments in the future. Genomic signatures obtained by gene expression profiling of EOC may be able to predict survival outcomes and other important clinical outcomes, such as the success of surgical treatment. Finally, genomic analyses may allow for the identification of novel predictive biomarkers for purposes of treatment planning. These data combined suggest a pathway to progress in the treatment of advanced ovarian cancer and the promise of fulfilling the objective of providing personalized medicine to women with ovarian cancer. Conclusions: The understanding of basic molecular events in the tumorigenesis and chemoresistance of EOC together with discovery of potential biomarkers may be greatly enhanced through large-scale genomic studies. In order to maximize the impact of these technologies, however, extensive validation studies are required. C1 [Krzystyniak, J.; Ceppi, L.; Birrer, M. J.] Massachusetts Gen Hosp, Ctr Canc Res, YAW-9-072,55 Fruit St, Boston, MA 02114 USA. [Dizon, D. S.; Birrer, M. J.] Massachusetts Gen Hosp, Ctr Canc, Div Gynecol Oncol, Boston, MA 02114 USA. [Dizon, D. S.; Birrer, M. J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, YAW-9-072,55 Fruit St, Boston, MA 02114 USA. EM mbirrer@partners.org OI Ceppi, Lorenzo/0000-0003-2597-9414 FU NCI [RC4CA156551-01, R01CA169200-03, R01CA142832-05]; Julie Fund FX The work was supported by NCI grants RC4CA156551-01, R01CA169200-03, R01CA142832-05 and generous support from The Julie Fund. NR 46 TC 1 Z9 1 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2016 VL 27 SU 1 BP 4 EP 10 DI 10.1093/annonc/mdw083 PG 7 WC Oncology SC Oncology GA DM1KC UT WOS:000376103100002 PM 27141069 ER PT J AU Leong, A Porneala, B Dupuis, J Florez, JC Meigs, JB AF Leong, Aaron Porneala, Bianca Dupuis, Josee Florez, Jose C. Meigs, James B. TI Type 2 Diabetes Genetic Predisposition, Obesity, and All-Cause Mortality Risk in the US: A Multiethnic Analysis SO DIABETES CARE LA English DT Article ID BODY-MASS INDEX; MENDELIAN RANDOMIZATION ANALYSIS; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; CARDIOVASCULAR-DISEASE; UNITED-STATES; POPULATION; ADULTS; PARADOX; ASSOCIATION AB OBJECTIVE Type 2 diabetes (T2D) is associated with increased mortality in ethnically diverse populations, although the extent to which this association is genetically determined is unknown. We sought to determine whether T2D-related genetic variants predicted all-cause mortality, even after accounting for BMI, in the Third National Health and Nutrition Examination Survey. RESEARCH DESIGN AND METHODS We modeled mortality risk using a genetic risk score (GRS) from a weighted sum of risk alleles at 38 T2D-related single nucleotide polymorphisms. In age-, sex-, and BMI-adjusted logistic regression models, accounting for the complex survey design, we tested the association with mortality in 6,501 participants. We repeated the analysis within ethnicities (2,528 non-Hispanic white [NHW], 1,979 non-Hispanic black [NHB], and 1,994 Mexican American [MA]) and within BMI categories (<25, 25-30, and >= 30 kg/m(2)). Significance was set at P < 0.05. RESULTS Over 17 years, 1,556 participants died. GRS was associated with mortality risk (OR 1.04 [95% CI 1.00-1.07] per T2D-associated risk allele, P = 0.05). Within ethnicities, GRS was positively associated with mortality risk in NHW and NHB, but not in MA (0.95 [0.90-1.01], P = 0.07). The negative trend in MA was largely driven by those with BMI <25 kg/m(2) (0.91 [0.82-1.00]). In NHW, the positive association was strongest among those with BMI >= 30 kg/m(2) (1.07 [1.02-1.12]). CONCLUSIONS In the U.S., a higher T2D genetic risk was associated with increased mortality risk, especially among obese NHW. The underlying genetic basis for mortality likely involves complex interactions with factors related to ethnicity, T2D, and body weight. C1 [Leong, Aaron; Porneala, Bianca; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Leong, Aaron; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Dupuis, Josee] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.; Meigs, JB (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM jmeigs@mgh.harvard.edu FU Canadian Diabetes Association postdoctoral research fellowship; National Institutes of Health [R01-DK078616]; National Institute of Diabetes and Digestive and Kidney Diseases [K24-DK-080140] FX A.L. is supported by a Canadian Diabetes Association postdoctoral research fellowship. J.D., J.C.F., and J.B.M. are supported by National Institutes of Health grant R01-DK078616. J.C.F. is a Massachusetts General Hospital Research Scholar. J.B.M. is supported in part by National Institute of Diabetes and Digestive and Kidney Diseases grant K24-DK-080140. NR 52 TC 2 Z9 2 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2016 VL 39 IS 4 BP 539 EP 546 DI 10.2337/dc15-2080 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DM3IP UT WOS:000376240400015 PM 26884474 ER PT J AU Weinstock, RS DuBose, SN Bergenstal, RM Chaytor, NS Peterson, C Olson, BA Munshi, MN Perrin, AJS Miller, KM Beck, RW Liljenquist, DR Aleppo, G Buse, JB Kruger, D Bhargava, A Goland, RS Edelen, RC Pratley, RE Peters, AL Rodriguez, H Ahmann, AJ Lock, JP Garg, SK Rickels, MR Hirsch, IB AF Weinstock, Ruth S. DuBose, Stephanie N. Bergenstal, Richard M. Chaytor, Naomi S. Peterson, Christina Olson, Beth A. Munshi, Medha N. Perrin, Alysa J. S. Miller, Kellee M. Beck, Roy W. Liljenquist, David R. Aleppo, Grazia Buse, John B. Kruger, Davida Bhargava, Anuj Goland, Robin S. Edelen, Rachel C. Pratley, Richard E. Peters, Anne L. Rodriguez, Henry Ahmann, Andrew J. Lock, John-Paul Garg, Satish K. Rickels, Michael R. Hirsch, Irl B. CA T1D Exchange Severe Hypoglycemia O TI Risk Factors Associated With Severe Hypoglycemia in Older Adults With Type 1 Diabetes SO DIABETES CARE LA English DT Article ID EXCHANGE CLINIC REGISTRY; BLOOD-GLUCOSE; INSULIN; FREQUENCY; AWARENESS; VALIDATION; SYMPTOMS; RECOVERY; MELLITUS; EPISODES AB OBJECTIVE Severe hypoglycemia is common in older adults with long-standing type 1 diabetes, but little is known about factors associated with its occurrence. RESEARCH DESIGN AND METHODS A case-control study was conducted at 18 diabetes centers in the T1D Exchange Clinic Network. Participants were >= 60 years old with type 1 diabetes for >= 20 years. Case subjects (n = 101) had at least one severe hypoglycemic event in the prior 12 months. Control subjects (n = 100), frequency-matched to case subjects by age, had no severe hypoglycemia in the prior 3 years. Data were analyzed for cognitive and functional abilities, social support, depression, hypoglycemia unawareness, various aspects of diabetes management, C-peptide level, glycated hemoglobin level, and blinded continuous glucose monitoring (CGM) metrics. RESULTS Glycated hemoglobin (mean 7.8% vs. 7.7%) and CGM-measured mean glucose (175 vs. 175 mg/dL) were similar between case and control subjects. More case than control subjects had hypoglycemia unawareness: only 11% of case subjects compared with 43% of control subjects reported always having symptoms associated with low blood glucose levels (P < 0.001). Case subjects had greater glucose variability than control subjects (P = 0.008) and experienced CGM glucose levels < 60 mg/dL for >= 20 min on 46% of days compared with 33% of days in control subjects (P = 0.10). On certain cognitive tests, case subjects scored worse than control subjects. CONCLUSIONS In older adults with long-standing type 1 diabetes, greater hypoglycemia unawareness and glucose variability are associated with an increased risk of severe hypoglycemia. A study to assess interventions to prevent severe hypoglycemia in high-risk individuals is needed. C1 [Weinstock, Ruth S.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [DuBose, Stephanie N.; Perrin, Alysa J. S.; Miller, Kellee M.; Beck, Roy W.] Jaeb Ctr Hlth Res, Tampa, FL USA. [Bergenstal, Richard M.; Olson, Beth A.] Pk Nicollet Int Diabet Ctr, Minneapolis, MN USA. [Chaytor, Naomi S.; Peterson, Christina; Hirsch, Irl B.] Univ Washington, Seattle, WA 98195 USA. [Munshi, Medha N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Liljenquist, David R.] Rocky Mt Diabet & Osteoporosis Ctr, Idaho Falls, ID USA. [Aleppo, Grazia] Northwestern Univ, Chicago, IL 60611 USA. [Buse, John B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Kruger, Davida] Henry Ford Med Ctr, Detroit, MI USA. [Bhargava, Anuj] Iowa Diabet & Endocrinol Res Ctr, Des Moines, IA USA. [Goland, Robin S.] Columbia Univ, Med Ctr, Naomi Berrie Diabet Ctr, New York, NY USA. [Edelen, Rachel C.] Reg Hlth Clin Res, Rapid City, SD USA. [Pratley, Richard E.] Florida Hosp, Diabet & Translat Res Inst Metab & Diabet, Orlando, FL USA. [Peters, Anne L.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Rodriguez, Henry] Univ S Florida, Tampa, FL USA. [Ahmann, Andrew J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lock, John-Paul] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. [Garg, Satish K.] Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [Rickels, Michael R.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Miller, KM (reprint author), Jaeb Ctr Hlth Res, Tampa, FL USA. EM t1dstats@jaeb.org FU Leona M. and Harry B. Helmsley Charitable Trust; National Institutes of Health FX Funding was provided by the Leona M. and Harry B. Helmsley Charitable Trust. The nonprofit employer of R.M.B. has received grant funding from the National Institutes of Health and the Leona M. and Harry B. Helmsley Charitable Trust. The nonprofit employer of N.S.C. has received grant funding from the National Institutes of Health. NR 35 TC 6 Z9 7 U1 3 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2016 VL 39 IS 4 BP 603 EP 610 DI 10.2337/dc15-1426 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DM3IP UT WOS:000376240400023 PM 26681721 ER PT J AU Judge, AM Bailey, R Behrman-Lippert, J Bailey, E Psaila, C Dickel, J AF Judge, Abigail M. Bailey, Rebecca Behrman-Lippert, JoAnn Bailey, Elizabeth Psaila, Cynthia Dickel, Jane TI The Transitioning Families Therapeutic Reunification Model in Nonfamilial Abductions SO FAMILY COURT REVIEW LA English DT Article DE Abduction; Mental Health Team; Reunification; Stockholm syndrome; and Transitioning Families ID SOCIAL SUPPORT; SEXUAL-ABUSE; CHILDREN; TRAUMA; ADOLESCENTS; SURVIVORS; PTSD AB The existing literature on abduction reunification is limited and evolving. Although guidelines for model service approaches exist, few programs address the unique challenges of reunifying children and families following abduction. This article delineates a family-based reunification model that has assisted families affected by abduction since 2006. Model components include a team-centered approach, a stage-oriented reunification process, and pitfalls and strategies related to intersystem collaboration. We present the value of a family-systems, solution-focused, trauma-informed, and case-specific approach to therapeutic reunification following child abduction. Evidence that is contrary to the popular notion of Stockholm's syndrome is also marked. Research on the efficacy of therapeutic reunification is essential for the growth of systems equipped to address the dynamic needs of these families. Accordingly, suggestions for evaluation research are proposed. Key Points for the Family Court Community: Families face a range of unique challenges during reunification following abduction. Historically, therapeutic reunification has emphasized the needs of the central victim with only a perfunctory focus on the family. This article delineates a family-based reunification model that has assisted families affected by abduction since 2006. We present the value of a family-system, solution-focused, trauma-informed, and case-specific approach to therapeutic reunification following child abduction. C1 [Judge, Abigail M.] Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. [Judge, Abigail M.; Bailey, Elizabeth] Univ Calif Los Angeles, Resnick Neuropsychiat Hosp, Los Angeles, CA 90024 USA. RP Judge, AM (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. EM abigailjudge@abigailjudge.com NR 57 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1531-2445 EI 1744-1617 J9 FAM COURT REV JI Fam. Court Rev. PD APR PY 2016 VL 54 IS 2 BP 232 EP 249 DI 10.1111/fcre.12215 PG 18 WC Law SC Government & Law GA DK1OS UT WOS:000374683100008 ER PT J AU Sepucha, KR Simmons, LH Barry, MJ Edgman-Levitan, S Licurse, AM Chaguturu, SK AF Sepucha, Karen R. Simmons, Leigh H. Barry, Michael J. Edgman-Levitan, Susan Licurse, Adam M. Chaguturu, Sreekanth K. TI Ten Years, Forty Decision Aids, And Thousands Of Patient Uses: Shared Decision Making At Massachusetts General Hospital SO HEALTH AFFAIRS LA English DT Article ID HEALTH; PERCEPTIONS; COSTS; HIP AB Shared decision making is a core component of population health strategies aimed at improving patient engagement. Massachusetts General Hospital's integration of shared decision making into practice has focused on the following three elements: developing a culture receptive to, and health care providers skilled in, shared decision making conversations; using patient decision aids to help inform and engage patients; and providing infrastructure and resources to support the implementation of shared decision making in practice. In the period 2005-15, more than 900 clinicians and other staff members were trained in shared decision making, and more than 28,000 orders for one of about forty patient decision aids were placed to support informed patient-centered decisions. We profile two different implementation initiatives that increased the use of patient decision aids at the hospital's eighteen adult primary care practices, and we summarize key elements of the shared decision making program. C1 [Sepucha, Karen R.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Sepucha, Karen R.; Simmons, Leigh H.; Chaguturu, Sreekanth K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barry, Michael J.; Edgman-Levitan, Susan] MGH, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. [Licurse, Adam M.] Brigham & Womens Phys Org, Boston, MA USA. [Licurse, Adam M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Licurse, Adam M.; Chaguturu, Sreekanth K.] Partners HealthCare, Populat Hlth Management, Boston, MA USA. [Chaguturu, Sreekanth K.] Harvard Univ, Sch Med, Boston, MA USA. RP Sepucha, KR (reprint author), Harvard Univ, Sch Med, Med, Boston, MA USA. EM ksepucha@mgh.harvard.edu FU Informed Medical Decisions Foundation; Massachusetts General Physicians Organization; Partners HealthCare; Gordon and Betty Moore Foundation; Patient-Centered Outcomes Research Institute (PCORI); Agency for Healthcare Research and Quality (AHRQ); National Heart, Lung, and Blood Institute; Massachusetts General Hospital from Healthwise; PCORI; AHRQ FX The work was supported by funding from the Informed Medical Decisions Foundation (now part of the nonprofit organization Healthwise), the Massachusetts General Physicians Organization, and Partners HealthCare. Karen Sepucha receives salary support as a medical editor for Healthwise and research support from the Gordon and Betty Moore Foundation; the Patient-Centered Outcomes Research Institute (PCORI); the Agency for Healthcare Research and Quality (AHRQ); and the National Heart, Lung, and Blood Institute. Michael Barry is an employee of and chief science officer at Healthwise and receives grant support through Massachusetts General Hospital from Healthwise. Susan Edgman-Levitan is a board member of Healthwise and receives research support from PCORI and AHRQ. NR 19 TC 3 Z9 3 U1 2 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD APR PY 2016 VL 35 IS 4 BP 630 EP 636 DI 10.1377/hlthaff.2015.1376 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DK2SG UT WOS:000374764100012 PM 27044963 ER PT J AU Ranard, BL Werner, RM Antanavicius, T Schwartz, HA Smith, RJ Meisel, ZF Asch, DA Ungar, LH Merchant, RM AF Ranard, Benjamin L. Werner, Rachel M. Antanavicius, Tadas Schwartz, H. Andrew Smith, Robert J. Meisel, Zachary F. Asch, David A. Ungar, Lyle H. Merchant, Raina M. TI Yelp Reviews Of Hospital Care Can Supplement And Inform Traditional Surveys Of The Patient Experience Of Care SO HEALTH AFFAIRS LA English DT Review ID SOCIAL MEDIA; PERFORMANCE; QUALITY; RATINGS AB Little is known about how real-time online rating platforms such as Yelp may complement the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, which is the US standard for evaluating patients' experiences after hospitalization. We compared the content of Yelp narrative reviews of hospitals to the topics in the HCAHPS survey, called domains in HCAHPS terminology. While the domains included in Yelp reviews covered the majority of HCAHPS domains, Yelp reviews covered an additional twelve domains not found in HCAHPS. The majority of Yelp topics that most strongly correlate with positive or negative reviews are not measured or reported by HCAHPS. The large collection of patient- and caregiver-centered experiences found on Yelp can be analyzed with natural language processing methods, identifying for policy makers the measures of hospital quality that matter most to patients and caregivers. The Yelp measures and analysis can also provide actionable feedback for hospitals. C1 [Ranard, Benjamin L.] Univ Penn, Med, Philadelphia, PA 19104 USA. [Ranard, Benjamin L.; Smith, Robert J.; Asch, David A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Univ Penn, Perelman Sch Med, Med, Philadelphia, PA 19104 USA. [Antanavicius, Tadas] Univ Penn, Philadelphia, PA 19104 USA. [Schwartz, H. Andrew] SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11794 USA. [Meisel, Zachary F.] Hosp Univ Penn, Emergency Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ungar, Lyle H.] Univ Penn, Dept Comp & Informat Sci, Philadelphia, PA 19104 USA. [Merchant, Raina M.] Univ Penn, Penn Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. [Merchant, Raina M.] Univ Penn, Emergency Med, Philadelphia, PA 19104 USA. RP Ranard, BL (reprint author), Univ Penn, Med, Philadelphia, PA 19104 USA. EM Raina.merchant@uphs.upenn.edu OI Smith, Robert James/0000-0001-9746-1230 FU National Institutes of Health [K23-10714038, K24-AG047908] FX Funding and support were provided by the National Institutes of Health, Grant No. K23-10714038 (for Raina M. Merchant) and Grant No. K24-AG047908 (for Rachel M. Werner). The study sponsors 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 article; or decision to submit the article for publication. The authors thank Judith A. Long (Perelman School of Medicine, University of Pennsylvania) for her review of the article and her insightful comments. She received no financial compensation. The opinions expressed are those of the authors and not the Department of Veterans Affairs. NR 36 TC 4 Z9 4 U1 4 U2 9 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD APR PY 2016 VL 35 IS 4 BP 697 EP 705 DI 10.1377/hlthaff.2015.1030 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DK2SG UT WOS:000374764100020 PM 27044971 ER PT J AU Maleki-Yazdi, M Singh, D Anzueto, A Tombs, L Naya, I Harris, S Iqbal, A Rolke, M AF Maleki-Yazdi, M. Singh, D. Anzueto, A. Tombs, L. Naya, I. Harris, S. Iqbal, A. Rolke, M. TI Clinically relevant Deterioration in COPD Patients under treatment with Umeclidinium/Vilanterol, Tiotropium or Placebo: Pooled Data SO INTERNIST LA German DT Meeting Abstract C1 [Maleki-Yazdi, M.] Univ Toronto, Womens Coll Hosp, Div Resp Med, Toronto, ON, Canada. [Singh, D.] Univ Manchester, Med Evaluat Unit, Manchester, Lancs, England. [Anzueto, A.] Audie L Murphy Hosp, San Antonio, TX USA. [Tombs, L.; Naya, I.] GlaxoSmithKline, Resp Med Dev Ctr, Stockley Pk, Uxbridge, Middx, England. [Harris, S.; Iqbal, A.] GlaxoSmithKline, Resp & Immunoinflammat Res, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0020-9554 EI 1432-1289 J9 INTERNIST JI Internist PD APR PY 2016 VL 57 SU 1 MA P038 BP S25 EP S25 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DL1UG UT WOS:000375417500045 ER PT J AU Tecilazich, F Feke, GT Mazzantini, S Sobrin, L Lorenzi, M AF Tecilazich, Francesco Feke, Gilbert T. Mazzantini, Sara Sobrin, Lucia Lorenzi, Mara TI Defective Myogenic Response of Retinal Vessels Is Associated With Accelerated Onset of Retinopathy in Type 1 Diabetic Individuals SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE type 1 diabetes; retinopathy; myogenic response; retinal blood flow; retinal circulation; laser Doppler; accelerator; biomarker ID BLOOD-FLOW; POSTURE CHANGE; PRESSURE; COMPLICATIONS; MELLITUS AB PURPOSE. We seek to identify pathogenic mechanisms for diabetic retinopathy that can become therapeutic targets beyond hyperglycemia and hypertension. We investigated if a defective myogenic response of retinal arteries to increased perfusion pressure, which exposes capillaries to increased pressure and flow, is associated with the onset of clinical retinopathy. METHODS. We examined prospectively the incidence of retinopathy in type 1 diabetic individuals tested 4 years earlier for the retinal arterial myogenic response, and in a cross-sectional study the prevalence of defective myogenic response in type 1 patients who had diabetic retinopathy. Among these, we contrasted early-onset (after 15 +/- 2 years of diabetes, E-DR; n = 5) to late-onset (after 26 +/- 3 years of diabetes, L-DR; n = 7) retinopathy. We measured the myogenic response using a laser Doppler blood flowmeter after a change in posture from sitting to reclining, which increases retinal perfusion pressure. RESULTS. Five of seven participants who 4 years prior had a defective myogenic response had now developed clinical retinopathy; as compared with only one of six participants who 4 years prior had a normal response (P = 0.10). In the cross-sectional study, all participants had normal retinal hemodynamics at steady state. In response to the postural change, only the EDR group showed defective myogenic response (P = 0.005 versus controls, P = 0.02 versus L-DR) and abnormally high retinal blood flow (P = 0.016 versus controls). CONCLUSIONS. In type 1 diabetic patients, a defective myogenic response of retinal arteries to pressure is not required for the development of clinical retinopathy, but is prominently associated with an accelerated onset of retinopathy. C1 [Tecilazich, Francesco; Mazzantini, Sara; Lorenzi, Mara] Harvard Univ, Sch Med, Massachusetts Eye & Ear, Schepens Eye Res Inst, Boston, MA USA. [Feke, Gilbert T.; Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Lorenzi, M (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM mara.lorenzi@schepens.harvard.edu FU OneSight Research Foundation (Dallas, TX, USA) FX Supported by the OneSight Research Foundation (Dallas, TX, USA). The authors alone are responsible for the content and the writing of the paper. NR 23 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2016 VL 57 IS 4 BP 1523 EP 1529 DI 10.1167/iovs.15-18356 PG 7 WC Ophthalmology SC Ophthalmology GA DL8XY UT WOS:000375926700003 PM 27035625 ER PT J AU Crnej, A Omoto, M Dohlman, TH Gonzalez-Andrades, M Paschalis, EI Cruzat, A Vu, THK Doorenbos, M Chen, DF Dohlman, CH Dana, R AF Crnej, Alja Omoto, Masahiro Dohlman, Thomas H. Gonzalez-Andrades, Miguel Paschalis, Eleftherios I. Cruzat, Andrea Vu, T. H. Khanh Doorenbos, Marianne Chen, Dong Feng Dohlman, Claes H. Dana, Reza TI Effect of Penetrating Keratoplasty and Keratoprosthesis Implantation on the Posterior Segment of the Eye SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE Boston keratoprosthesis; keratoplasty; chronic inflammation; optic neuropathy ID BOSTON KERATOPROSTHESIS; WALLERIAN DEGENERATION; I KERATOPROSTHESIS; MOUSE MODEL; GLAUCOMA; MULTICENTER; TITANIUM; OUTCOMES; SURGERY AB PURPOSE. To compare the effects of post-penetrating keratoplasty (PK) and post-keratoprosthesis (KPro) surgery-related inflammation on the posterior segment of the eye and to assess inhibition of tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on these effects. METHODS. BALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were transplanted onto BALB/C host beds as part of PK or miniature KPro (m-KPro) implantation. Intraocular pressure (IOP) was measured via an intracameral pressure sensor; tissues were harvested and analyzed 8 weeks after surgery. Expression of TNF alpha and IL-1 beta in the retina was analyzed using real-time quantitative (q)PCR. Optic nerve degeneration (axon count, circularity, and area) was assessed quantitatively using ImageJ software. After m-KPro implantation, mice were treated with saline, anti-TNF alpha, or anti-IL-1 beta antibody, and axonal loss was assessed after 10 weeks. RESULTS. Mean IOP was within normal limits in the operated and fellow eyes in all groups. The mRNA expression of TNFa and IL-1 beta was highest in m-KPro groups with either syngeneic or an allogeneic carrier. We observed optic nerve degeneration in both allogeneic PK and m-KPro implanted eyes with an allogeneic carrier. However, TNFa blockade significantly reduced axonal loss by 35%. CONCLUSIONS. Allogeneic PK and m-KPro implants with an allogeneic carrier lead to chronic inflammation in the posterior segment of the eye, resulting in optic nerve degeneration. In addition, blockade of TNFa prevents axonal degeneration in this preclinical model of allogeneic m-KPro (alloKPro) implantation. C1 [Crnej, Alja; Omoto, Masahiro; Dohlman, Thomas H.; Gonzalez-Andrades, Miguel; Paschalis, Eleftherios I.; Cruzat, Andrea; Vu, T. H. Khanh; Doorenbos, Marianne; Chen, Dong Feng; Dohlman, Claes H.; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Dept Ophthalmol,Med Sch, Boston, MA 02114 USA. RP Dana, R (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU Boston-KPro research fund; National Institutes of Health [R01-EY 12963] FX Supported by the Boston-KPro research fund and National Institutes of Health Grant R01-EY 12963. NR 26 TC 1 Z9 1 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2016 VL 57 IS 4 BP 1643 EP 1648 DI 10.1167/iovs.15-17557 PG 6 WC Ophthalmology SC Ophthalmology GA DL8XY UT WOS:000375926700016 PM 27054516 ER PT J AU Woodell, A Jones, BW Williamson, T Schnabolk, G Tomlinson, S Atkinson, C Rohrer, B AF Woodell, Alex Jones, Bryan W. Williamson, Tucker Schnabolk, Gloriane Tomlinson, Stephen Atkinson, Carl Rohrer, Baerbel TI A Targeted Inhibitor of the Alternative Complement Pathway Accelerates Recovery From Smoke-Induced Ocular Injury SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE alternative complement pathway; CR2-fH; knockout mouse; smoke exposure; mitochondria; Bruch's membrane deposits; dry age-related macular degeneration ID RETINAL-PIGMENT EPITHELIUM; CAUSES OXIDATIVE DAMAGE; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; CIGARETTE-SMOKE; CHOROIDAL NEOVASCULARIZATION; MEDIATED INJURY; RPE CELLS; STRESS; ACTIVATION AB PURPOSE. Morphologic and genetic evidence exists that an overactive complement system driven by the complement alternative pathway (AP) is involved in pathogenesis of age-related macular degeneration (AMD). Smoking is the only modifiable risk factor for AMD. As we have shown that smoke-related ocular pathology can be prevented in mice that lack an essential activator of AP, we ask here whether this pathology can be reversed by increasing inhibition in AP. METHODS. Mice were exposed to either cigarette smoke (CS) or filtered air (6 hours/day, 5 days/week, 6 months). Smoke-exposed animals were then treated with the AP inhibitor (CR2-fH) or vehicle control (PBS) for the following 3 months. Spatial frequency and contrast sensitivity were assessed by optokinetic response paradigms at 6 and 9 months; additional readouts included assessment of retinal morphology by electron microscopy (EM) and gene expression analysis by quantitative RT-PCR. RESULTS. The CS mice treated with CR2-fH showed significant improvement in contrast threshold compared to PBS-treated mice, whereas spatial frequency was unaffected by CS or pharmacologic intervention. Treatment with CR2-fH in CS animals reversed thinning of the retina observed in PBS-treated mice as analyzed by spectral-domain optical coherence tomography, and reversed most morphologic changes in RPE and Bruch's membrane seen in CS animals by EM. CONCLUSIONS. Taken together, these findings suggest that AP inhibitors not only prevent, but have the potential to accelerate the clearance of complement-mediated ocular injury. Improving our understanding of the regulation of the AP is paramount to developing novel treatment approaches for AMD. C1 [Woodell, Alex; Rohrer, Baerbel] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Jones, Bryan W.] Univ Utah, Moran Eye Ctr, Salt Lake City, UT USA. [Williamson, Tucker; Tomlinson, Stephen; Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave, Charleston, SC 29425 USA. [Schnabolk, Gloriane; Tomlinson, Stephen; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. [Atkinson, Carl] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA. RP Atkinson, C (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave, Charleston, SC 29425 USA.; Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA. EM atkinsoc@musc.edu; rohrer@musc.edu FU National Institutes of Health (NIH) [R01EY019320, R01 NHLBI 091944, NIH EY015128, NIH EY02576, EY014800]; Department of Veterans Affairs [I01 RX000444]; Research to Prevent Blindness (RPB), Inc., New York, New York, United States; Vision Core from Research to Prevent Blindness; Edward N. and Della L. Thome Memorial Foundation; NIH [C06 RR015455] FX Supported in part by National Institutes of Health (NIH) Grants R01EY019320, R01 NHLBI 091944, NIH EY015128, NIH EY02576, and EY014800; Department of Veterans Affairs I01 RX000444; an unrestricted grant to the Medical University of South Carolina from Research to Prevent Blindness (RPB), Inc., New York, New York, United States; Vision Core, an unrestricted grant from Research to Prevent Blindness to the Moran Eye Center; Edward N. and Della L. Thome Memorial Foundation grant for Age-Related Macular Degeneration Research. Animal studies were conducted in a facility constructed with support from the NIH (C06 RR015455). CA, ST, and BR are patent holders for the use of CR2-fH in complement-dependent diseases. This patent is licensed to Alexion Therapeutics. NR 46 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2016 VL 57 IS 4 BP 1728 EP 1737 DI 10.1167/iovs.15-18471 PG 10 WC Ophthalmology SC Ophthalmology GA DL8XY UT WOS:000375926700027 PM 27064393 ER PT J AU Zhou, CX Lei, FY Chodosh, J Paschalis, EI AF Zhou, Chengxin Lei, Fengyang Chodosh, James Paschalis, Eleftherios I. TI The Role of Titanium Surface Microtopography on Adhesion, Proliferation, Transformation, and Matrix Deposition of Corneal Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE titanium; biocompatibility; implants; cornea; surface roughness; alpha-smooth muscle actin; collagen deposition ID BOSTON TYPE-1 KERATOPROSTHESIS; IN-VITRO; DIFFERENTIATION; FIBROBLASTS; EXPRESSION; OUTCOMES; KINASE; MYOFIBROBLASTS; ENDOTHELIUM; TOPOGRAPHY AB PURPOSE. Titanium (Ti) is an excellent implantable biomaterial that can be further enhanced by surface topography optimization. Despite numerous data from orthopedics and dentistry, the effect of Ti surface topography on ocular cells is still poorly understood. In light of the recent adaptation of Ti in the Boston Keratoprosthesis artificial cornea, we attempted to perform an extended evaluation of the effect of Ti surface topography on corneal cell adhesion, proliferation, cytotoxicity, transformation, and matrix deposition. METHODS. Different surface topographies were generated on medical grade Ti-6Al-4V-ELI (extra-low interstitial), with linearly increased roughness (polished to grit blasted). Biological response was evaluated in vitro using human corneal limbal epithelial (HCLE) cells, stromal fibroblasts (HCF), and endothelial cells (HCEnC). RESULTS. None of the Ti surface topographies caused cytotoxicity to any of the three corneal cell types. However, rough Ti surface inhibited HCLE and HCF cell adhesion and proliferation, while HCEnC proliferation was unaffected. Long-term experiments with HCF revealed that rough Ti surface with R-a (the arithmetic average of the profile height from the mean line) >= 1.15 mu m suppressed HCF focal adhesion kinase phosphorylation, changed fibroblast morphology, and caused less aligned and reduced deposition of collagen matrix as compared to smooth Ti (R-a <= 0.08 mu m). In the presence of transforming growth factor beta 1 (TGF beta 1) stimulation, rough Ti inhibited alpha-smooth muscle actin (alpha-SMA) expression and collagen deposition, leading to decreased myofibroblast transformation and disorganization of the collagen fibrils as compared to smooth Ti. CONCLUSIONS. This study suggests that Ti surface topography regulates corneal cell behavior in a tissue-dependent manner that varies across the corneal strata. Contrary to the accepted paradigm, smooth surface topography can enhance cell adhesion and proliferation and increase matrix deposition by corneal cells. C1 [Paschalis, Eleftherios I.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Boston Keratoprosthesis Lab, 243 Charles St, Boston, MA 02114 USA. [Paschalis, Eleftherios I.] Harvard Univ, Sch Med, Schepens Eye Res Inst, 243 Charles St, Boston, MA 02114 USA. [Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. RP Paschalis, EI (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Boston Keratoprosthesis Lab, 243 Charles St, Boston, MA 02114 USA.; Paschalis, EI (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 243 Charles St, Boston, MA 02114 USA.; Chodosh, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM James_Chodosh@meei.harvard.edu; eleftherios_paschalis@meei.harvard.edu FU Boston Keratoprosthesis Research Fund; Massachusetts Eye and Ear; Eleanor and Miles Shore Fund FX Supported by the Boston Keratoprosthesis Research Fund, Massachusetts Eye and Ear, and the Eleanor and Miles Shore Fund. All authors are full-time employees of Massachusetts Eye and Ear Infirmary, a nonprofit organization that is the manufacturer of the Boston Keratoprosthesis. The authors alone are responsible for the content and writing of the paper. NR 51 TC 0 Z9 0 U1 4 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2016 VL 57 IS 4 BP 1927 EP 1938 DI 10.1167/iovs.15-18406 PG 12 WC Ophthalmology SC Ophthalmology GA DL8XY UT WOS:000375926700053 PM 27092719 ER PT J AU Liu, CL Vojnovic, D Kochevar, IE Jurkunas, UV AF Liu, Cailing Vojnovic, Dijana Kochevar, Irene E. Jurkunas, Ula V. TI UV-A Irradiation Activates Nrf2-Regulated Antioxidant Defense and Induces p53/Caspase3-Dependent Apoptosis in Corneal Endothelial Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE corneal endothelial cells; ultraviolet A; Nrf2; p53; oxidative stress ID OXIDATIVE-STRESS; N-ACETYLCYSTEINE; HUMAN SKIN; HUMAN KERATINOCYTES; FUCHS DYSTROPHY; PROTECTIVE ROLE; P53 PROTEIN; IN-VITRO; NRF2; EXPRESSION AB PURPOSE. To examine whether Nrf2-regulated antioxidant defense and p53 are activated in human corneal endothelial cells (CEnCs) by environmental levels of ultraviolet A (UV-A), a known stimulator of oxidative stress. METHODS. Immortalized human CEnCs (HCEnCi) were exposed to UV-A fluences of 2.5, 5, 10, or 25 J/cm(2), then allowed to recover for 3 to 24 hours. Control HCEnCi did not receive UV-A. Reactive oxygen species (ROS) were measured using H(2)DCFDA. Cell cytotoxicity was evaluated by lactate dehydrogenase (LDH) release. Levels of Nrf2, HO-1, NQO-1, p53, and caspase3 were detected by immunnoblotting or real-time PCR. Activated caspase3 was measured by immunoblotting and a fluorescence assay. RESULTS. Exposure of HCEnCi to 5, 10, and 25 J/cm(2) UV-A increased ROS levels compared with controls. Nrf2, HO-1, and NQO-1 mRNA increased 1.7- to 3.2-fold at 3 and 6 hours after irradiation with 2.5 and 5 J/cm(2) UV-A. At 6 hours post irradiation, UV-A (5 J/cm(2)) enhanced nuclear Nrf2 translocation. At 24 hours post treatment, UV-A (5, 10, and 25 J/cm(2)) produced a 1.8- to 2.8-fold increase in phospho-p53 and a 2.6- to 6.0-fold increase in activated caspase3 compared with controls, resulting in 20% to 42% cell death. CONCLUSIONS. Lower fluences of UV-A induce Nrf2-regulated antioxidant defense and higher fluences activate p53 and caspase3, indicating that even near-environmental levels of UV-A may affect normal CEnCs. This data suggest that UV-A may especially damage cells deficient in antioxidant defense, and thus may be involved in the etiology of Fuchs' endothelial corneal dystrophy (FECD). C1 [Liu, Cailing; Vojnovic, Dijana; Jurkunas, Ula V.] Harvard Univ, Sch Med, Massachusetts Eye & Ear, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. [Kochevar, Irene E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Jurkunas, UV (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM ula_jurkunas@meei.harvard.edu FU National Institutes Health/National Eye Institutes (Bethesda, MD, USA) [R01 EY20581]; Research to Prevent Blindness Award (New York, NY, USA) FX Supported by grants from National Institutes Health/National Eye Institutes R01 EY20581 (Bethesda, MD, USA) and Research to Prevent Blindness Award (UVJ; New York, NY, USA). NR 49 TC 1 Z9 1 U1 2 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2016 VL 57 IS 4 BP 2319 EP 2327 DI 10.1167/iovs.16-19097 PG 9 WC Ophthalmology SC Ophthalmology GA DL8XY UT WOS:000375926700097 PM 27127932 ER PT J AU Monteleone, PP Jaffer, FA AF Monteleone, Peter P. Jaffer, Farouc A. TI Side-Branch Occlusions in Coronary CTO-PCI: Avoid or Forget? SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Editorial Material ID IN-HOSPITAL OUTCOMES; PROCEDURAL OUTCOMES; UNITED-STATES; REGISTRY; INTERVENTION; REVASCULARIZATION C1 [Monteleone, Peter P.; Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Cardiac Catheterizat Lab, Boston, MA 02114 USA. RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 EI 1557-2501 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD APR PY 2016 VL 28 IS 4 BP 174 EP 175 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DM5OX UT WOS:000376400400012 PM 27031939 ER PT J AU Hulsmans, M Sam, F Nahrendorf, M AF Hulsmans, Maarten Sam, Flora Nahrendorf, Matthias TI Monocyte and macrophage contributions to cardiac remodeling SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Review DE Monocytes; Macrophages; Myocardial infarction; Hemodynamic stress; Fibrosis; Cardiac remodeling ID ACUTE MYOCARDIAL-INFARCTION; PRESERVED EJECTION FRACTION; GENE-EXPRESSION PROFILES; HEMATOPOIETIC STEM-CELLS; HEART-FAILURE; TISSUE MACROPHAGES; STEADY-STATE; IN-VIVO; INFLAMMATORY MONOCYTES; LY-6C(HIGH) MONOCYTES AB The mammalian heart contains a population of resident macrophages that expands in response to myocardial infarction and hemodynamic stress. This expansion occurs likely through both local macrophage proliferation and monocyte recruitment. Given the role of macrophages in tissue remodeling, their contribution to adaptive processes in the heart is conceivable but currently poorly understood. In this review, we discuss monocyte and macrophage heterogeneity associated with cardiac stress, the cell's potential contribution to the pathogenesis of cardiac fibrosis, and describe different tools to study and characterize these innate immune cells. Finally, we highlight their potential role as therapeutic targets. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Hulsmans, Maarten; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. [Hulsmans, Maarten; Nahrendorf, Matthias] Harvard Univ, Sch Med, 185 Cambridge St, Boston, MA 02114 USA. [Sam, Flora] Boston Univ, Whitaker Cardiovasc Inst, Sch Med, 715 Albany St, Boston, MA 02118 USA. RP Nahrendorf, M (reprint author), Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU National Institutes of Health [R01HL114477, R01HL117829, R01HL096576]; Fonds voor Wetenschappelijk Onderzoek-Vlaanderen FX This work has been funded in whole or in part with federal funds from the National Institutes of Health R01HL114477, R01HL117829, and R01HL096576. Maarten Hulsmans was funded by the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen. NR 94 TC 11 Z9 11 U1 4 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD APR PY 2016 VL 93 BP 149 EP 155 DI 10.1016/j.yjmcc.2015.11.015 PG 7 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA DM1ZL UT WOS:000376145300019 PM 26593722 ER PT J AU Bradshaw, AD AF Bradshaw, Amy D. TI The role of secreted protein acidic and rich in cysteine (SPARC) in cardiac repair and fibrosis: Does expression of SPARC by macrophages influence outcomes? SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Matricellular; Inflammation; Collagen; Extracellular matrix; Osteonectin; BM40 ID FIBRILLAR COLLAGEN CONTENT; DIASTOLIC FUNCTION ROLE; EXTRACELLULAR-MATRIX; MYOCARDIAL-INFARCTION; INFLAMMATION; DEPOSITION; CARCINOMA; LEUKOCYTE; MONOCYTE; DERMIS AB Secreted protein acidic and rich in cysteine (SPARC) is a matricellular, collagen-binding protein. Matricellular proteins are described as extracellular matrix-associated proteins that do not serve classical structural roles in the matrix such as those ascribed to laminins and collagens. The family of matricellular proteins modulates cell:extracellular matrix interactions and is actively expressed during tissue remodeling. Functional activities attributed to SPARC in cultured cells include regulation of cell adhesion, cytoskeletal rearrangement, proliferation, and matrix assembly. The primary phenotype characteristic of SPARC-null mice is a deficit in amounts of fibrillar collagen and fibril morphology. Strikingly, SPARC-null mice demonstrate a blunted fibrotic response in a number of different tissue settings. The role of monocyte/macrophages as an important component of tissue fibrosis is becoming increasingly appreciated. Expression of SPARC by bone marrow derived inflammatory cells raises the interesting proposition that SPARC produced by infiltrating leukocytes might contribute to the course of inflammation and tissue fibrosis in the heart. This review will summarize results from studies defining the function of SPARC in myocardial repair and fibrosis and results from other non-cardiac tissues that shed light onto possible consequences of SPARC expression by monocyte/macrophages in the setting of heart disease. (C) 2015 Published by Elsevier Ltd. C1 [Bradshaw, Amy D.] Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, MSC 773, Charleston, SC 29425 USA. [Bradshaw, Amy D.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Bradshaw, AD (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, MSC 773, Charleston, SC 29425 USA.; Bradshaw, AD (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. EM bradshad@musc.edu OI Bradshaw, Amy/0000-0002-9202-3044 FU Veterans Affairs Merit Award [BX001385]; American Heart Association Award [12GRNT12060193] FX This work was supported by a Veterans Affairs Merit Award (BX001385) and an American Heart Association Award (12GRNT12060193). NR 32 TC 4 Z9 4 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD APR PY 2016 VL 93 BP 156 EP 161 DI 10.1016/j.yjmcc.2015.11.014 PG 6 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA DM1ZL UT WOS:000376145300020 PM 26582465 ER PT J AU Yi, Y Merfeld, DM AF Yi, Yongwoo Merfeld, Daniel M. TI A quantitative confidence signal detection model: 1. Fitting psychometric functions SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE thresholds; decision-making; confidence rating; confidence calibration ID ADAPTIVE PSYCHOPHYSICAL PROCEDURES; SENSORY DISCRIMINATION; SEQUENTIAL ESTIMATION; EFFICIENT ESTIMATION; GENERAL KNOWLEDGE; DETECTION TASKS; CALIBRATION; THRESHOLDS; JUDGMENTS; UNDERCONFIDENCE AB Perceptual thresholds are commonly assayed in the laboratory and clinic. When precision and accuracy are required, thresholds are quantified by fitting a psychometric function to forced-choice data. The primary shortcoming of this approach is that it typically requires 100 trials or more to yield accurate (i.e., small bias) and precise (i.e., small variance) psychometric parameter estimates. We show that confidence probability judgments combined with a model of confidence can yield psychometric parameter estimates that are markedly more precise and/or markedly more efficient than conventional methods. Specifically, both human data and simulations show that including confidence probability judgments for just 20 trials can yield psychometric parameter estimates that match the precision of those obtained from 100 trials using conventional analyses. Such an efficiency advantage would be especially beneficial for tasks (e.g., taste, smell, and vestibular assays) that require more than a few seconds for each trial, but this potential benefit could accrue for many other tasks. C1 [Yi, Yongwoo; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Rm 421, Boston, MA 02114 USA. [Yi, Yongwoo; Merfeld, Daniel M.] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Rm 421, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu FU National Institute of Child Health and Human Development [R01-DC-04158, R56-DC-12038] FX This research was supported by National Institute of Child Health and Human Development Grants R01-DC-04158 and R56-DC-12038. NR 65 TC 1 Z9 1 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR 1 PY 2016 VL 115 IS 4 BP 1932 EP 1945 DI 10.1152/jn.00318.2015 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA DM0SU UT WOS:000376056900006 PM 26763777 ER PT J AU Fidler, R Johnson, M AF Fidler, Richard Johnson, Meshell TI Human Factors Approach to Comparative Usability of Hospital Manual Defibrillators SO RESUSCITATION LA English DT Article DE Defibrillator; Resuscitation equipment; Simulation; AED; Transcutaneous pacing; Synchronized cardioversion ID CARDIAC-ARREST; UNITED-STATES; SURVIVAL AB Introduction: Equipment-related issues have recently been cited as a significant contributor to the suboptimal outcomes of resuscitation management. A systematic evaluation of the human-device interface was undertaken to evaluate the intuitive nature of three different defibrillators. Devices tested were the Physio-Control LifePak 15, the Zoll R Series Plus, and the Philips MRx. Methods: A convenience sample of 73 multidisciplinary health care providers from 5 different hospitals participated in this study. All subjects' performances were evaluated without any training on the devices being studied to assess the intuitiveness of the user interface to perform the functions of delivering an Automated External Defibrillator (AED) shock, a manual defibrillation, pacing to achieve 100% capture, and synchronized cardioversion on a rhythm simulator. Results: Times to deliver an AED shock were fastest with the Zoll, whereas the Philips had the fastest times to deliver a manual defibrillation. Subjects took the least time to attain 100% capture for pacing with the Physio-Control device. No differences in performance times were seen with synchronized cardioversion among the devices. Human factors issues uncovered during this study included a preference for knobs over soft keys and a desire for clarity in control panel design. This study demonstrated no clearly superior defibrillator, as each of the models exhibited strengths in different areas. When asked their defibrillator preference, 67% of subjects chose the Philips. Conclusions: This comparison of user interfaces of defibrillators in simulated situations allows the assessment of usability that can provide manufacturers and educators with feedback about defibrillator implementation for these critical care devices. Published by Elsevier Ireland Ltd C1 [Fidler, Richard; Johnson, Meshell] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Johnson, Meshell] Univ Calif San Francisco, Northern Calif Inst Res & Educ, San Francisco, CA 94121 USA. [Fidler, Richard] Univ Calif San Francisco, Sch Nursing, Dept Anesthesia, San Francisco, CA 94121 USA. [Fidler, Richard] Univ Calif San Francisco, Sch Nursing, Dept Perioperat Med, San Francisco, CA 94121 USA. [Johnson, Meshell] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. RP Fidler, R (reprint author), San Francisco VA Med Ctr, Dept Anesthesia, 4150 Clement St, San Francisco, CA 94121 USA.; Fidler, R (reprint author), San Francisco VA Med Ctr, Dept Perioperat Med, 4150 Clement St, San Francisco, CA 94121 USA. EM richard.fidler@ucsf.edu FU San Francisco Department of Veterans Affairs Medical Center FX The San Francisco Department of Veterans Affairs Medical Center supported this work. Philips Healthcare, Physio-Control, and Zoll Medical provided equipment support. NR 10 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD APR PY 2016 VL 101 BP 71 EP 76 DI 10.1016/j.resuscitation.2016.01.029 PG 6 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA DL8HR UT WOS:000375882300025 PM 26868076 ER PT J AU Butt, H Yetisen, AK Mistry, D Khan, SA Hassan, MU Yun, SH AF Butt, Haider Yetisen, Ali K. Mistry, Denika Khan, Safyan Akram Hassan, Mohammed Umair Yun, Seok Hyun TI Morpho Butterfly-Inspired Nanostructures SO ADVANCED OPTICAL MATERIALS LA English DT Article ID STRUCTURAL COLOR; HOLOGRAPHIC SENSORS; PHOTONIC NANOSENSOR; LASER-ABLATION; SCALES; WINGS; LIGHT; DEVICES; IRREGULARITY; REPLICATION AB The wing scales of Morpho butterflies contain 3D nanostructures that produce blue iridescent colors. Incident light is diffracted from multilayered nanostructures to create interference effects and diffract narrow-band light. The intensity of the diffracted light remains high over a wide range of viewing angles. Structural coloration originating from the scales of Morpho wing nanostructures has been studied to analyze its optical properties and to produce scalable replicas. This review discusses computational and experimental methods to replicate these nanoarchitectures. Analytical and numerical methods utilized include multilayer models, the finite element method, and rigorous coupled-wave analysis, which enable the optimization of nanofabrication techniques involving biotemplating, chemical vapour deposition, electron beam lithography, and laser patterning to mimic the wing scale nanostructure. Dynamic tunability of the morphology, refractive index, and chemical composition of the Morpho wing scales allows the realization of a numerous applications. C1 [Butt, Haider; Mistry, Denika] Univ Birmingham, Sch Engn, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. [Yetisen, Ali K.; Yun, Seok Hyun] Harvard Univ, Sch Med, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.; Yun, Seok Hyun] MIT, Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Khan, Safyan Akram] King Fahd Univ Petr & Minerals, Ctr Excellence Nanotechnol, Dhahran 31261, Saudi Arabia. [Hassan, Mohammed Umair] COMSATS Inst Informat Technol, Dept Phys, Islamabad, Pakistan. RP Butt, H (reprint author), Univ Birmingham, Sch Engn, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. EM h.butt@bham.ac.uk RI Khan, Safyan/B-8520-2015; OI Khan, Safyan/0000-0002-7759-7066; Butt, Haider/0000-0003-2434-9525 FU Leverhulme Trust FX H. Butt, A. K. Yetisen, and D. Mistry wrote the article. D. Mistry, S. A. Khan, M. U. Hassan, and S. H. Yun edited the manuscript. H. Butt and A. K. Yetisen contributed equally to this work. The authors declare no competing financial interests. H. Butt thanks the Leverhulme Trust for the research funding. NR 62 TC 2 Z9 2 U1 17 U2 39 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 2195-1071 J9 ADV OPT MATER JI Adv. Opt. Mater. PD APR PY 2016 VL 4 IS 4 BP 497 EP 504 DI 10.1002/adom.201500658 PG 8 WC Materials Science, Multidisciplinary; Optics SC Materials Science; Optics GA DK1RU UT WOS:000374692300001 ER PT J AU Peng, C Luttmann-Gibson, H Zanobetti, A Cohen, A De Souza, C Coull, BA Horton, ES Schwartz, J Koutrakis, P Gold, DR AF Peng, Cheng Luttmann-Gibson, Heike Zanobetti, Antonella Cohen, Allison De Souza, Celine Coull, Brent A. Horton, Edward S. Schwartz, Joel Koutrakis, Petros Gold, Diane R. TI Air pollution influences on exhaled nitric oxide among people with type II diabetes SO AIR QUALITY ATMOSPHERE AND HEALTH LA English DT Article DE Air pollution; Fraction of exhaled nitric oxide; Diabetes mellitus; Epidemiology; Particles ID ULTRAFINE PARTICLES; ASTHMA; EXPOSURE; AMBIENT; INFLAMMATION; INCREASES; CHILDREN; DISEASE; OZONE; ASSOCIATION AB In a population with type 2 diabetes mellitus (T2DM), we examined the associations of short-term air pollutant exposures with pulmonary inflammation, measured as fraction of exhaled pulmonary nitric oxide (FeNO). Sixty-nine Boston Metropolitan residents with T2DM completed up to five biweekly visits with 321 offline FeNO measurements. We measured ambient concentrations of particle mass, number, and components at our stationary central site. Ambient concentrations of gaseous air pollutants were obtained from state monitors. We used linear models with fixed effects for participants, adjusting for 24-h mean temperature, 24-h mean water vapor pressure, season, and scrubbed room NO the day of the visit, to estimate the associations between FeNO and interquartile range (IQR) increases in exposure. Interquartile increases in the 6-h averages of black carbon (BC) (0.5 mu g/m(3)) and particle number (PN) (1000 particles/cm(3)) were associated with increases in FeNO of 3.84 % (95 % CI = 0.60 to 7.18 %) and 9.86 % (95 % CI = 3.59 to 16.52 %), respectively. We also found significant associations of increases in FeNO with increases in 24-h moving averages of BC, PN, and nitrogen oxides (NOx). Recent studies have focused on FeNO as a marker for eosinophilic pulmonary inflammation in asthmatic populations. This study adds support to the relevance of FeNO as a marker for pulmonary inflammation in diabetic populations, whose underlying chronic inflammatory status is likely to be related to innate immunity and proinflammatory adipokines. C1 [Peng, Cheng; Luttmann-Gibson, Heike; Zanobetti, Antonella; De Souza, Celine; Schwartz, Joel; Koutrakis, Petros; Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Cohen, Allison; Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Gold, Diane R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Schwartz, Joel; Gold, Diane R.] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Peng, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM chp950@mail.harvard.edu FU NIEHS [PO1 ES-09825, R21 ES-020194-01]; US EPA [RD-83241601, RD-83479801] FX This study is funded by NIEHS PO1 ES-09825, NIEHS R21 ES-020194-01, US EPA RD-83241601, and US EPA RD-83479801. The contents of this publication are solely the responsibility of the grantee and do not necessarily represent the official views of the US EPA. Further, US EPA does not endorse the purchase of any commercial products or services mentioned in the publication. The authors are grateful to all participants of the study and the staff responsible for data collection. NR 37 TC 2 Z9 2 U1 2 U2 4 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1873-9318 EI 1873-9326 J9 AIR QUAL ATMOS HLTH JI Air Qual. Atmos. Health PD APR PY 2016 VL 9 IS 3 BP 265 EP 273 DI 10.1007/s11869-015-0336-5 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA DK1IE UT WOS:000374664900006 PM 27213020 ER PT J AU Rosario, M Li, F Wypij, D Roberts, AL Corliss, HL Charlton, BM Frazier, AL Austin, SB AF Rosario, Margaret Li, Fei Wypij, David Roberts, Andrea L. Corliss, Heather L. Charlton, Brittany M. Frazier, A. Lindsay Austin, S. Bryn TI Disparities by Sexual Orientation in Frequent Engagement in Cancer-Related Risk Behaviors: A 12-Year Follow-Up SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; HEPATITIS-B-VIRUS; OF-THE-LITERATURE; SUBSTANCE USE; UNITED-STATES; MENTAL-HEALTH; YOUNG-ADULTS; TRANSMITTED INFECTIONS; PHYSICAL-ACTIVITY; TOBACCO USE AB Objectives. We examined sexual-orientation disparities in frequent engagement in cancer-related risk indicators of tobacco, alcohol, diet and physical activity, ultraviolet radiation, and sexually transmitted infections (STIs). Methods. We used longitudinal data from the national Growing Up Today Study (19992010). Of the analytic sample (n = 9958), 1.8% were lesbian or gay (LG), 1.6% bisexual (BI), 12.1% mostly heterosexual (MH), and 84.5% completely heterosexual (CH). Results. More sexual minorities (LGs, BIs, and MHs) than CHs frequently engaged in multiple cancer-related risk behaviors (33%, 29%, 28%, and 19%, respectively). Sexual-minority young women, especially BI and MH, more frequently engaged over time in substance use and diet and physical activity risk than CH women. More young gay than CH men frequently engaged over time in vomiting for weight control (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.1, 9.4), being physically inactive (OR = 1.7; 95% CI = 1.2, 2.4), and using tanning booths (OR = 4.7; 95% CI = 3.0, 7.4), and had a higher prevalence of ever having an STI (OR = 3.5; 95% CI = 2.0, 6.4). Individual analyses were generally comparable to the group-level analyses. Conclusions. Young sexual minorities are at risk for cancer through frequent exposure to cancer-related risk behaviors over time. Long-term, longitudinal studies and surveillance data are essential and warranted to track frequent engagement in the risk behaviors and cancer-related morbidity and mortality. C1 [Rosario, Margaret] CUNY City Coll, Dept Psychol, NAC Bldg 7-120,Convent Ave & 138th St, New York, NY 10031 USA. [Rosario, Margaret] CUNY, Grad Ctr, Dept Psychol, NAC Bldg 7-120,Convent Ave & 138th St, New York, NY 10031 USA. [Li, Fei; Wypij, David] Harvard TH Chan Sch Publ Hlth HSPH, Dept Biostat, Boston, MA USA. [Wypij, David; Charlton, Brittany M.; Frazier, A. Lindsay; Austin, S. Bryn] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wypij, David] Bostons Childrens Hosp, Dept Cardiol, Boston, MA USA. [Roberts, Andrea L.] HSPH, Dept Social & Behav Sci, Boston, MA USA. [Corliss, Heather L.] San Diego State Univ, Div Hlth Promot & Behav Sci, San Diego, CA 92182 USA. [Charlton, Brittany M.; Austin, S. Bryn] Boston Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Frazier, A. Lindsay] HSPH, Dept Epidemiol, Boston, MA USA. [Austin, S. Bryn] Brigham & Womens Hosp, HMS, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Rosario, M (reprint author), CUNY City Coll, Dept Psychol, NAC Bldg 7-120,Convent Ave & 138th St, New York, NY 10031 USA.; Rosario, M (reprint author), CUNY, Grad Ctr, Dept Psychol, NAC Bldg 7-120,Convent Ave & 138th St, New York, NY 10031 USA. EM mrosario@gc.cuny.edu FU National Institutes of Health [HD45763, HD57368]; Robert Wood Johnson Foundation; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [T32HD060454] FX The report is based on the Growing Up Today Study cohort, which has been funded by grants HD45763 and HD57368 from the National Institutes of Health and the Robert Wood Johnson Foundation. B. Charlton was supported by the Training Grant T32HD060454 in Reproductive, Perinatal, and Pediatric Epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 118 TC 1 Z9 1 U1 12 U2 17 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2016 VL 106 IS 4 BP 698 EP 706 DI 10.2105/AJPH.2015.302977 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DL8SY UT WOS:000375913000038 PM 26794176 ER PT J AU Dossett, ML Davis, RB Kaptchuk, TJ Yeh, GY AF Dossett, Michelle L. Davis, Roger B. Kaptchuk, Ted J. Yeh, Gloria Y. TI Homeopathy Use by US Adults: Results of a National Survey SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MEDICINE AB We used the 2012 National Health Interview Survey to compare homeopathy users with supplement users and those using other forms of complementary and integrative medicine. Among US adults, 2.1% used homeopathy within the past 12 months. Respiratory and otorhinolaryngology complaints were most commonly treated (18.5%). Homeopathy users were more likely to use multiple complementary and integrative medicine therapies and to perceive the therapy as helpful than were supplement users. US homeopathy use remains uncommon; however, users perceive it as helpful. C1 [Dossett, Michelle L.; Davis, Roger B.; Kaptchuk, Ted J.; Yeh, Gloria Y.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Davis, Roger B.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Kaptchuk, Ted J.] Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA. [Kaptchuk, Ted J.] Harvard Univ, Sch Med, Boston, MA USA. RP Dossett, ML (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, 151 Merrimac St,4th Floor, Boston, MA 02114 USA. EM mdossett@mgh.harvard.edu FU Harvard Catalyst, the Harvard Clinical and Translational Science Center; National Institutes of Health (NIH) [1UL1 TR001102-01]; Harvard University and its affiliated academic health care centers; Institutional National Research Service Award from the National Center for Complementary and Integrative Health (NCCIH) at the NIH [T32 AT000051]; Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center; NCCIH [K24 AT004095] FX This work was supported by Harvard Catalyst, the Harvard Clinical and Translational Science Center, the National Institutes of Health (NIH; award 1UL1 TR001102-01), and Harvard University and its affiliated academic health care centers. M. L. Dossett was supported by an Institutional National Research Service Award (T32 AT000051) from the National Center for Complementary and Integrative Health (NCCIH) at the NIH and by the Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center. T.J. Kaptchuk was supported by the NCCIH (award K24 AT004095). NR 20 TC 0 Z9 0 U1 2 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2016 VL 106 IS 4 BP 743 EP 745 DI 10.2105/AJPH.2015.303025 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DL8SY UT WOS:000375913000045 PM 26890179 ER PT J AU Spector, M AF Spector, Myron TI The living legacy of a biomaterials founder: remembering Samuel F Hulbert, PhD OBITUARY SO BIOMEDICAL MATERIALS LA English DT Biographical-Item C1 [Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. RP Spector, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. EM mspector@bwh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 EI 1748-605X J9 BIOMED MATER JI Biomed. Mater. PD APR PY 2016 VL 11 IS 2 AR 020202 DI 10.1088/1748-6041/11/2/020202 PG 2 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA DL3GY UT WOS:000375523400002 PM 27001792 ER PT J AU Dimopoulos, M Lonial, S White, D Moreau, P Palumbo, A San Miguel, J Shpilberg, O Anderson, K Grosicki, S Spicka, I Walter-Croneck, A Magen-Nativ, H Mateos, MV Reece, D Beksac, M Bleickardt, E Poulart, V Katz, J Singhal, A Richardson, P AF Dimopoulos, M. Lonial, S. White, D. Moreau, P. Palumbo, A. San Miguel, J. Shpilberg, O. Anderson, K. Grosicki, S. Spicka, I. Walter-Croneck, A. Magen-Nativ, H. Mateos, M-V Reece, D. Beksac, M. Bleickardt, E. Poulart, V. Katz, J. Singhal, A. Richardson, P. TI ELOQUENT-2: Extended safety and efficacy follow-up of the phase 3, randomized, open-label study of elotuzumab in combination with lenalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 36th World Congress of the International-Society-of-Hematology CY APR 18-21, 2016 CL British Soc Haematol, Glasgow, SCOTLAND SP Int Soc Hematol HO British Soc Haematol C1 [Dimopoulos, M.] Univ Athens, Dept Clin Therapeut, Athens 11528, Greece. [Lonial, S.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. [White, D.] QEII Hlth Sci Ctr, Div Hematol, Halifax, NS, Canada. [White, D.] Dalhousie Univ, Halifax, NS, Canada. [Moreau, P.] Univ Hosp, Dept Haematol, Nantes, France. [Palumbo, A.] AOU San Giovanni Battista Torino Osped Molinette, Div Hematol, Turin, Italy. [San Miguel, J.] Univ Navarra Clin, CIMA, IDISNA, Clin & Translat Med, Pamplona, Spain. [Shpilberg, O.] Assuta Med Ctr, Inst Haematol, Tel Aviv, Israel. [Anderson, K.] Dana Farber Canc Inst, Hematol Oncol Treatment Ctr, Boston, MA 02115 USA. [Grosicki, S.] Silesian Med Univ, Dept Canc Prevent, Katowice, Poland. [Spicka, I.] Charles Univ Hosp, Dept Clin Haematol, Prague, Czech Republic. [Walter-Croneck, A.] Med Univ Lublin, Dept Haematooncol & Bone Marrow Transplantat, Lublin, Poland. [Magen-Nativ, H.] Rabin Med Ctr, Davidoff Canc Ctr, Petah Tiqwa, Israel. [Magen-Nativ, H.] Tel Aviv Univ, Ramat Aviv, Israel. [Mateos, M-V] Univ Hosp Salamanca, IBSAL, Dept Haematol, Salamanca, Spain. [Reece, D.] Princess Margaret Canc Ctr, Dept Med Oncol & Haematol, Toronto, ON, Canada. [Beksac, M.] Ankara Univ, Dept Haematol, TR-06100 Ankara, Turkey. [Bleickardt, E.] Bristol Myers Squibb Co, Med Oncol & Hematol, 5 Res Pkwy, Wallingford, CT 06492 USA. [Poulart, V.] Bristol Myers Squibb Co, Global Biostat, Braine Lalleud, Belgium. [Katz, J.] Bristol Myers Squibb Co, Global Clin Res, Res & Dev, Princeton, NJ USA. [Singhal, A.] AbbVie Biotherapeut Inc ABR, Redwood City, CA USA. [Richardson, P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2016 VL 173 SU 1 SI SI MA 3 BP 6 EP 7 PG 2 WC Hematology SC Hematology GA DJ9OX UT WOS:000374543900004 ER PT J AU Dimopoulos, MA Trotman, J Tedeschi, A Matous, JV Macdonald, D Tam, C Tournilhac, O Ma, S Oriol, A Heffner, LT Shustik, C Garcia-Sanz, R Cornell, RF de Larrea, CF Castillo, JJ Granell, M Kyrtsonis, MC Leblond, V Symeonidis, A Singh, P Li, J Graef, T Bilotti, E Treon, S Buske, C AF Dimopoulos, M. A. Trotman, J. Tedeschi, A. Matous, J. V. Macdonald, D. Tam, C. Tournilhac, O. Ma, S. Oriol, A. Heffner, L. T. Shustik, C. Garcia-Sanz, R. Cornell, R. F. Fernandez de Larrea, C. Castillo, J. J. Granell, M. Kyrtsonis, M. C. Leblond, V. Symeonidis, A. Singh, P. Li, J. Graef, T. Bilotti, E. Treon, S. Buske, C. CA iNNOVATETM Investigators TI Efficacy and safety of single-agent ibrutinib in rituximab-refractory patients with Waldenstrom's macroglobulinemia (WM): Initial results from an international, multicenter, open-label phase 3 substudy (iNNOVATE (TM)) SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 36th World Congress of the International-Society-of-Hematology CY APR 18-21, 2016 CL British Soc Haematol, Glasgow, SCOTLAND SP Int Soc Hematol HO British Soc Haematol C1 [Dimopoulos, M. A.] Univ Athens, Sch Med, Athens 11528, Greece. [Trotman, J.] Univ Sydney, Concord Hosp, Concord, Australia. [Tedeschi, A.] Osped Niguarda Ca Granda, Milan, Italy. [Matous, J. V.] Colorado Blood Canc Inst, Denver, CO USA. [Macdonald, D.] Dalhousie Univ, Halifax, NS, Canada. [Tam, C.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Tam, C.] St Vincents Hosp, Melbourne, Vic, Australia. [Tournilhac, O.] CHU Clermont Ferrand, Hematol Clin Adulte & Therapie Cellulaire, Clermont Ferrand, France. [Tournilhac, O.] CHU Clermont Ferrand, Hematol Clin Adulte & Therapie Cellulaire, Clermont Ferrand, France. [Ma, S.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Oriol, A.] Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Barcelona, Spain. [Heffner, L. T.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Shustik, C.] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. [Garcia-Sanz, R.] Hosp Univ Salamanca, Salamanca, Spain. [Cornell, R. F.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Fernandez de Larrea, C.] Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain. [Castillo, J. J.; Treon, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Granell, M.] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Kyrtsonis, M. C.] Univ Athens, Sch Med, Athens, Spain. [Leblond, V.] UPMC Univ Paris, Hop Pitie Salpetriere APHP, Paris, France. [Symeonidis, A.] Univ Patras, Sch Med, GR-26110 Patras, Greece. [Singh, P.; Li, J.; Graef, T.; Bilotti, E.] Pharmacyclics LLC, Sunnyvale, CA USA. [Buske, C.] Univ Hosp Ulm, Inst Expt Canc Res, Comprehens Canc Ctr Ulm, Ulm, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2016 VL 173 SU 1 SI SI MA 195 BP 82 EP 82 PG 1 WC Hematology SC Hematology GA DJ9OX UT WOS:000374543900195 ER PT J AU Coutre, S Barrientos, J Brown, J De Vos, S Furman, R Keating, M O'Brien, S Pagel, J Sharman, J Zelenetz, A Newcomb, T Cho, Y Aguilar, C Dreiling, L AF Coutre, S. Barrientos, J. Brown, J. De Vos, S. Furman, R. Keating, M. O'Brien, S. Pagel, J. Sharman, J. Zelenetz, A. Newcomb, T. Cho, Y. Aguilar, C. Dreiling, L. TI Safety of idelalisib in B-cell malignancies: Integrated analysis of eight clinical trials SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 36th World Congress of the International-Society-of-Hematology CY APR 18-21, 2016 CL British Soc Haematol, Glasgow, SCOTLAND SP Int Soc Hematol HO British Soc Haematol C1 [Coutre, S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Barrientos, J.] Hofstra North Shore LIJ Sch Med, New Hyde Pk, NY USA. [Brown, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [De Vos, S.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Furman, R.] Weill Cornell Med Coll, New York, NY USA. [Keating, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [O'Brien, S.] Chao Family Comprehens Canc Ctr, Orange, CA USA. [Pagel, J.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Sharman, J.] US Oncol, Springfield, IL USA. [Sharman, J.] Willamette Valley Canc Inst, Springfield, IL USA. [Zelenetz, A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Newcomb, T.; Cho, Y.; Aguilar, C.; Dreiling, L.] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2016 VL 173 SU 1 SI SI MA 234 BP 97 EP 98 PG 2 WC Hematology SC Hematology GA DJ9OX UT WOS:000374543900234 ER PT J AU Jones, JA Wach, M Robak, T Brown, J Menter, A Vandenberghe, E Ysebaert, L Wagner-Johnston, N Polikoff, J Salman, H Taylor, KM Coutre, S Spurgeon, SEF Kendall, S Flinn, I Dreiling, L Dubowy, R Cho, Y Peterman, S Owen, C AF Jones, J. Alan Wach, M. Robak, T. Brown, J. Menter, A. Vandenberghe, E. Ysebaert, L. Wagner-Johnston, N. Polikoff, J. Salman, H. Taylor, K. M. Coutre, S. Spurgeon, S. E. F. Kendall, S. Flinn, I. Dreiling, L. Dubowy, R. Cho, Y. Peterman, S. Owen, C. TI Results of a phase III randomized, controlled study evaluating the efficacy and safety of idelalisib in combination with ofatumumab (OFA) for previously treated patients with CLL SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 36th World Congress of the International-Society-of-Hematology CY APR 18-21, 2016 CL British Soc Haematol, Glasgow, SCOTLAND SP Int Soc Hematol HO British Soc Haematol C1 [Jones, J. Alan] Ohio State Univ, Columbus, OH 43210 USA. [Wach, M.] Med Univ Lublin, Lublin, Poland. [Robak, T.] Med Univ Lodz, Lodz, Poland. [Brown, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Menter, A.] Kaiser Permanente Med Grp, Denver, CO USA. [Vandenberghe, E.] St James Hosp, Dublin 8, Ireland. [Ysebaert, L.] CHU Toulouse, Toulouse, France. [Wagner-Johnston, N.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Polikoff, J.] Kaiser Hosp San Diego, San Marcos, CA USA. [Salman, H.] GRU Canc Ctr, Augusta, GA USA. [Taylor, K. M.] Haematol & Oncol Clin Australia Mater, South Brisbane, Australia. [Coutre, S.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA. [Spurgeon, S. E. F.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kendall, S.] UCS Canc Ctr, Utah Canc Specialists, Salt Lake City, UT USA. [Flinn, I.] Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA. [Dreiling, L.; Dubowy, R.; Cho, Y.; Peterman, S.] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. [Owen, C.] Alberta Hlth Serv, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2016 VL 173 SU 1 SI SI MA 236 BP 98 EP 98 PG 1 WC Hematology SC Hematology GA DJ9OX UT WOS:000374543900236 ER PT J AU Cook, G Cella, D Durie, B Goldschmidt, H Kuter, D Moreau, P Vij, R Davis, C Oukessou, A Zyczynski, T Popov, S Palumbo, A AF Cook, G. Cella, D. Durie, B. Goldschmidt, H. Kuter, D. Moreau, P. Vij, R. Davis, C. Oukessou, A. Zyczynski, T. Popov, S. Palumbo, A. TI An ongoing multinational observational study in multiple myeloma (PREAMBLE): Preliminary report on patient survival SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 36th World Congress of the International-Society-of-Hematology CY APR 18-21, 2016 CL British Soc Haematol, Glasgow, SCOTLAND SP Int Soc Hematol HO British Soc Haematol C1 [Cook, G.] Univ Leeds, Sect Expt Haematol, Leeds LS2 9JT, W Yorkshire, England. [Cella, D.] Northwestern Univ, Dept Med Social Sci, Evanston, IL USA. [Durie, B.] Cedars Sinai Med Ctr, Samuel Oschin Canc Ctr, Los Angeles, CA 90048 USA. [Goldschmidt, H.] Univ Heidelberg Hosp, Dept Hematol & Oncol, Heidelberg, Germany. [Kuter, D.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol, Boston, MA USA. [Moreau, P.] Univ Hosp Nantes, Dept Haematol, Nantes, France. [Vij, R.] Washington Univ, Sch Med, Div Hematol & Oncol, St Louis, MO USA. [Davis, C.; Zyczynski, T.] Bristol Myers Squibb Co, Worldwide Hlth Econ & Outcomes Res, Princeton, NJ USA. [Oukessou, A.] Bristol Myers Squibb Co, Global Med Affairs Oncol & Hematol, Princeton, NJ USA. [Popov, S.] Parexel, Biostat, St Petersburg, Russia. [Palumbo, A.] Osped Molinette, AOU San Giovanni Battista Torino, Dept Haematol, Turin, Italy. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2016 VL 173 SU 1 SI SI MA 270 BP 111 EP 112 PG 2 WC Hematology SC Hematology GA DJ9OX UT WOS:000374543900270 ER PT J AU Nandakumar, SK Ulirsch, JC Sankaran, VG AF Nandakumar, Satish K. Ulirsch, Jacob C. Sankaran, Vijay G. TI Advances in understanding erythropoiesis: evolving perspectives SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE erythropoiesis; haematopoiesis; haemopoietic progenitors; red cell disorders; red cells ID DIAMOND-BLACKFAN ANEMIA; HEMATOPOIETIC STEM-CELLS; FETAL-HEMOGLOBIN EXPRESSION; GENOME-WIDE ASSOCIATION; BETA-THALASSEMIA; INEFFECTIVE ERYTHROPOIESIS; HEREDITARY SPHEROCYTOSIS; PRIMITIVE ERYTHROBLASTS; TERMINAL ERYTHROPOIESIS; ERYTHROID PROGENITORS AB Red blood cells (RBCs) are generated from haematopoietic stem and progenitor cells (HSPCs) through the step-wise process of differentiation known as erythropoiesis. In this review, we discuss our current understanding of erythropoiesis and highlight recent advances in this field. During embryonic development, erythropoiesis occurs in three distinct waves comprising first, the yolk sac-derived primitive RBCs, followed sequentially by the erythro-myeloid progenitor (EMP) and HSPC-derived definitive RBCs. Recent work has highlighted the complexity and variability that may exist in the hierarchical arrangement of progenitors responsible for erythropoiesis. Using recently defined cell surface markers, it is now possible to enrich for erythroid progenitors and precursors to a much greater extent than has been possible before. While a great deal of knowledge has been gained on erythropoiesis from model organisms, our understanding of this process is currently being refined through human genetic studies. Genes mutated in erythroid disorders can now be identified more rapidly by the use of next-generation sequencing techniques. Genome-wide association studies on erythroid traits in healthy populations have also revealed new modulators of erythropoiesis. All of these recent developments have significant promise not only for increasing our understanding of erythropoiesis, but also for improving our ability to intervene when RBC production is perturbed in disease. C1 [Nandakumar, Satish K.; Ulirsch, Jacob C.; Sankaran, Vijay G.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Hematol Oncol, Boston, MA 02115 USA. [Nandakumar, Satish K.; Ulirsch, Jacob C.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Nandakumar, Satish K.; Ulirsch, Jacob C.; Sankaran, Vijay G.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Sankaran, VG (reprint author), Boston Childrens Hosp, 3 Blackfan Circle,CLS 03001, Boston, MA 02115 USA. EM sankaran@broadinstitute.org FU National Institutes of Health [R01 DK103794, R21 HL120791, U01 HL117720] FX We apologize to all the authors whose work we were unable to specifically discuss due to space constraints. We thank all the members of the Sankaran laboratory for their valuable input. This work was supported by the National Institutes of Health grants R01 DK103794, R21 HL120791, and U01 HL117720 to V.G. Sankaran. NR 100 TC 4 Z9 4 U1 7 U2 16 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 APR PY 2016 VL 173 IS 2 BP 206 EP 218 DI 10.1111/bjh.13938 PG 13 WC Hematology SC Hematology GA DJ9VI UT WOS:000374560800003 PM 26846448 ER PT J AU Kadoch, C AF Kadoch, Cigall TI Lifting Up the HAT: Synthetic Lethal Screening Reveals a Novel Vulnerability at the CBP-p300 Axis SO CANCER DISCOVERY LA English DT Editorial Material ID CANCERS; MUTATIONS; COMPLEXES; BRG1 AB Cancer genotype-specific synthetic lethal vulnerabilities represent promising therapeutic targets. In this issue of Cancer Discovery, Ogiwara and colleagues uncover a synthetic lethal relationship between two histone acetyl transferase paralogs, CBP and p300, highlighting that cancer cells deficient in CBP are uniquely sensitized to genetic and chemical inhibition of p300. (C) 2016 AACR. C1 [Kadoch, Cigall] Dana Farber Canc Inst, 450 Brookline Ave,Dana Bldg,Room 620, Boston, MA 02215 USA. [Kadoch, Cigall] Harvard Univ, Sch Med, 450 Brookline Ave,Dana Bldg,Room 620, Boston, MA 02215 USA. [Kadoch, Cigall] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Kadoch, C (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana Bldg,Room 620, Boston, MA 02215 USA.; Kadoch, C (reprint author), Harvard Univ, Sch Med, 450 Brookline Ave,Dana Bldg,Room 620, Boston, MA 02215 USA. EM Cigall_kadoch@dfci.harvard.edu FU NCI NIH HHS [DP2 CA195762] NR 11 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2016 VL 6 IS 4 BP 350 EP 352 DI 10.1158/2159-8290.CD-16-0163 PG 3 WC Oncology SC Oncology GA DL7TU UT WOS:000375843800019 PM 27045018 ER PT J AU Sherr, CJ Beach, D Shapiro, GI AF Sherr, Charles J. Beach, David Shapiro, Geoffrey I. TI Targeting CDK4 and CDK6: From Discovery to Therapy SO CANCER DISCOVERY LA English DT Review ID DEPENDENT KINASE 4/6; RETINOBLASTOMA GENE-PRODUCT; ADVANCED BREAST-CANCER; CELL-CYCLE CONTROL; HUMAN TUMOR XENOGRAFTS; INHIBITOR PALBOCICLIB; SUSCEPTIBILITY GENE; ANTITUMOR-ACTIVITY; PROTEIN-KINASE; PD 0332991 AB Biochemical and genetic characterization of D-type cyclins, their cyclin D-dependent kinases (CDK4 and CDK6), and the polypeptide CDK4/6 inhibitor p16(INK4) over two decades ago revealed how mammalian cells regulate entry into the DNA synthetic (S) phase of the cell-division cycle in a retinoblastoma protein-dependent manner. These investigations provided proof-of-principle that CDK4/6 inhibitors, particularly when combined with coinhibition of allied mitogen-dependent signal transduction pathways, might prove valuable in cancer therapy. FDA approval of the CDK4/6 inhibitor palbociclib used with the aromatase inhibitor letrozole for breast cancer treatment highlights long-sought success. The newest findings herald clinical trials targeting other cancers. Significance: Rapidly emerging data with selective inhibitors of CDK4/6 have validated these cell-cycle kinases as anticancer drug targets, corroborating longstanding preclinical predictions. This review addresses the discovery of these CDKs and their regulators, as well as translation of CDK4/6 biology to positive clinical outcomes and development of rational combinatorial therapies. (C) 2015 AACR. C1 [Sherr, Charles J.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Sherr, Charles J.] St Jude Childrens Res Hosp, Dept Tumor Cell Biol, 332 N Lauderdale St, Memphis, TN 38105 USA. [Beach, David] Barts & London Queen Marys Sch Med & Dent, Blizard Inst, London, England. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Early Drug Dev Ctr, Boston, MA 02115 USA. RP Sherr, CJ; Shapiro, GI (reprint author), Dana Farber Canc Inst, Mayer 446,450 Brookline Ave, Boston, MA 02215 USA. EM sherr@stjude.org; geoffrey_shapiro@dfci.harvard.edu FU Howard Hughes Medical Institute; NIH Cancer Center [CA-21765]; ALSAC of St. Jude Children's Research Hospital; NIH [R01-CA090687, P50-CA168504]; Susan G. Komen investigator-initiated research grant [IIR12223953]; Pfizer FX C.J. Sherr is supported by the Howard Hughes Medical Institute, by NIH Cancer Center core grant CA-21765, and by ALSAC of St. Jude Children's Research Hospital. G.I. Shapiro is supported by NIH grants R01-CA090687 and P50-CA168504 and Susan G. Komen investigator-initiated research grant IIR12223953, and receives research funding from Pfizer. NR 137 TC 37 Z9 38 U1 15 U2 30 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2016 VL 6 IS 4 BP 353 EP 367 DI 10.1158/2159-8290.CD-15-0894 PG 15 WC Oncology SC Oncology GA DL7TU UT WOS:000375843800020 PM 26658964 ER PT J AU Elf, S Abdelfattah, NS Chen, E Perales-Paton, J Rosen, EA Ko, A Peisker, F Florescu, N Giannini, S Wolach, O Morgan, EA Tothova, Z Losman, JA Schneider, RK Al-Shahrour, F Mullally, A AF Elf, Shannon Abdelfattah, Nouran S. Chen, Edwin Perales-Paton, Javier Rosen, Emily A. Ko, Amy Peisker, Fabian Florescu, Natalie Giannini, Silvia Wolach, Ofir Morgan, Elizabeth A. Tothova, Zuzana Losman, Julie-Aurore Schneider, Rebekka K. Al-Shahrour, Fatima Mullally, Ann TI Mutant Calreticulin Requires Both Its Mutant C-terminus and the Thrombopoietin Receptor for Oncogenic Transformation SO CANCER DISCOVERY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE JAK2; GAIN-OF-FUNCTION; MYELOPROLIFERATIVE NEOPLASMS; POLYCYTHEMIA-VERA; CYTOKINE RECEPTOR; ESSENTIAL THROMBOCYTHEMIA; ACTIVATING MUTATION; MYELOID METAPLASIA; QUALITY-CONTROL AB Somatic mutations in calreticulin (CALR) are present in approximately 40% of patients with myeloproliferative neoplasms (MPN), but the mechanism by which mutant CALR is oncogenic remains unclear. Here, we demonstrate that expression of mutant CALR alone is sufficient to engender MPN in mice and recapitulates the disease phenotype of patients with CALR-mutant MPN. We further show that the thrombopoietin receptor MPL is required for mutant CALR-driven transformation through JAK-STAT pathway activation, thus rendering mutant CALR-transformed hematopoietic cells sensitive to JAK2 inhibition. Finally, we demonstrate that the oncogenicity of mutant CALR is dependent on the positive electrostatic charge of the C-terminus of the mutant protein, which is necessary for physical interaction between mutant CALR and MPL. Together, our findings elucidate a novel paradigm of cancer pathogenesis and reveal how CALR mutations induce MPN. SIGNIFICANCE: The mechanism by which CALR mutations induce MPN remains unknown. In this report, we show that the positive charge of the CALR mutant C-terminus is necessary to transform hematopoietic cells by enabling binding between mutant CALR and the thrombopoietin receptor MPL. (C) 2016 AACR. C1 [Elf, Shannon; Abdelfattah, Nouran S.; Chen, Edwin; Rosen, Emily A.; Ko, Amy; Peisker, Fabian; Florescu, Natalie; Giannini, Silvia; Wolach, Ofir; Tothova, Zuzana; Schneider, Rebekka K.; Mullally, Ann] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dept Med, Boston, MA 02115 USA. [Perales-Paton, Javier; Al-Shahrour, Fatima] Spanish Natl Canc Res Ctr CNIO, Clin Res Programme, Translat Bioinformat Unit, Madrid, Spain. [Morgan, Elizabeth A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tothova, Zuzana; Losman, Julie-Aurore; Mullally, Ann] Broad Inst, Cambridge, MA USA. [Tothova, Zuzana; Losman, Julie-Aurore; Mullally, Ann] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RP Mullally, A (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM amullally@partners.org OI Morgan, Elizabeth/0000-0001-5880-9337 FU NIH [K08 HL109734]; Damon Runyon clinical investigator award; MPNRF; Jeanne D. Housman Fund for Research on Myeloproliferative Disorders; T32 molecular hematology training award (NHLBI); Lady Tata Memorial Trust Award; ASH Physician-Scientist Career Development Award; ASH HONORS award FX This work was supported by the NIH (K08 HL109734 to A. Mullally), a Damon Runyon clinical investigator award (A. Mullally), MPNRF (A. Mullally), and the Jeanne D. Housman Fund for Research on Myeloproliferative Disorders (A. Mullally). S. Elf is a recipient of a T32 molecular hematology training award (NHLBI), E. Chen is a recipient of a Lady Tata Memorial Trust Award, and E. A. Rosen is a recipient of an ASH Physician-Scientist Career Development Award and an ASH HONORS award. NR 45 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2016 VL 6 IS 4 BP 368 EP 381 DI 10.1158/2159-8290.CD-15-1434 PG 14 WC Oncology SC Oncology GA DL7TU UT WOS:000375843800021 PM 26951227 ER PT J AU Miller, MA Oudin, MJ Sullivan, RJ Wang, SJ Meyer, AS Im, H Frederick, DT Tadros, J Griffith, LG Lee, H Weissleder, R Flaherty, KT Gertler, FB Lauffenburger, DA AF Miller, Miles A. Oudin, Madeleine J. Sullivan, Ryan J. Wang, Stephanie J. Meyer, Aaron S. Im, Hyungsoon Frederick, Dennie T. Tadros, Jenny Griffith, Linda G. Lee, Hakho Weissleder, Ralph Flaherty, Keith T. Gertler, Frank B. Lauffenburger, Douglas A. TI Reduced Proteolytic Shedding of Receptor Tyrosine Kinases Is a Post-Translational Mechanism of Kinase Inhibitor Resistance SO CANCER DISCOVERY LA English DT Article ID NEGATIVE BREAST-CANCER; TUMOR MICROENVIRONMENT; ADAPTIVE RESISTANCE; THERAPEUTIC TARGET; MEK INHIBITION; EGF RECEPTOR; AXL KINASE; ADAM10; ACTIVATION; CELLS AB Kinase inhibitor resistance often involves upregulation of poorly understood "bypass" signaling pathways. Here, we show that extracellular proteomic adaptation is one path to bypass signaling and drug resistance. Proteolytic shedding of surface receptors, which can provide negative feedback on signaling activity, is blocked by kinase inhibitor treatment and enhances bypass signaling. In particular, MEK inhibition broadly decreases shedding of multiple receptor tyrosine kinases (RTK), including HER4, MET, and most prominently AXL, an ADAM10 and ADAM17 substrate, thus increasing surface RTK levels and mitogenic signaling. Progression-free survival of patients with melanoma treated with clinical BRAF/MEK inhibitors inversely correlates with RTK shedding reduction following treatment, as measured noninvasively in blood plasma. Disrupting protease inhibition by neutralizing TIMP1 improves MAPK inhibitor efficacy, and combined MAPK/AXL inhibition synergistically reduces tumor growth and metastasis in xenograft models. Altogether, extracellular proteomic rewiring through reduced RTK shedding represents a surprising mechanism for bypass signaling in cancer drug resistance. SIGNIFICANCE: Genetic, epigenetic, and gene expression alterations often fail to explain adaptive drug resistance in cancer. This work presents a novel post-translational mechanism of such resistance: Kinase inhibitors, particularly targeting MAPK signaling, increase tumor cell surface receptor levels due to widely reduced proteolysis, allowing tumor signaling to circumvent intended drug action. (C) 2016 AACR. C1 [Miller, Miles A.; Wang, Stephanie J.; Meyer, Aaron S.; Griffith, Linda G.; Lauffenburger, Douglas A.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Miller, Miles A.; Im, Hyungsoon; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Oudin, Madeleine J.; Meyer, Aaron S.; Tadros, Jenny; Gertler, Frank B.; Lauffenburger, Douglas A.] MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Sullivan, Ryan J.; Flaherty, Keith T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Div Med Oncol,Med Sch, Boston, MA 02114 USA. [Frederick, Dennie T.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Gertler, Frank B.; Lauffenburger, Douglas A.] MIT, Dept Biol, Cambridge, MA USA. RP Lauffenburger, DA (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM lauffen@mit.edu RI Im, Hyungsoon/A-3178-2009 OI Im, Hyungsoon/0000-0002-0626-1346 FU NIH [U54-CA112967, R01-CA096504]; Department of Defense [W81XWH-13-1-0031] FX This work was supported by NIH grants U54-CA112967 and R01-CA096504 (to D.A. Lauffenburger), and Department of Defense award W81XWH-13-1-0031 (to M.J. Oudin). NR 59 TC 10 Z9 10 U1 4 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2016 VL 6 IS 4 BP 382 EP 399 DI 10.1158/2159-8290.CD-15-0933 PG 18 WC Oncology SC Oncology GA DL7TU UT WOS:000375843800022 PM 26984351 ER PT J AU Tucker, NR Clauss, S Ellinor, PT AF Tucker, Nathan R. Clauss, Sebastian Ellinor, Patrick T. TI Common variation in atrial fibrillation: navigating the path from genetic association to mechanism SO CARDIOVASCULAR RESEARCH LA English DT Review DE Atrial fibrillation; Genetics; Mechanism; Epigenetics; SNP ID PARALLEL REPORTER ASSAY; FAMILIAL AGGREGATION; SYSTEMATIC DISSECTION; CHROMOSOME 4Q25; IN-SITU; VARIANTS; RISK; EXPRESSION; POLYMORPHISM; RECURRENCE AB Atrial fibrillation (AF) is the most common cardiac arrhythmia with well-established clinical and genetic risk components. Genome-wide association studies (GWAS) have identified 17 independent susceptibility signals for AF at 14 genomic regions, but the mechanisms through which these loci confer risk to AF remain largely undefined. This problem is not unique to AF, as the field of functional genomics, which attempts to bridge this gap from genotype to phenotype, has only uncovered the mechanisms for a handful of GWAS loci. Recent functional genomic studies have made great strides towards translating genetic discoveries to an underlying mechanism, but the large-scale application of these techniques to AF has remain limited. These advances, as well as the continued unresolved challenges for both common variation in AF and the functional genomics field in general, will be the subject of the following review. C1 [Tucker, Nathan R.; Clauss, Sebastian; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Clauss, Sebastian] Univ Munich, Med Klin & Poliklin 1, Campus Grosshadern, Munich, Germany. [Clauss, Sebastian] DZHK German Ctr Cardiovasc Res, Gottingen, Germany. [Ellinor, Patrick T.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.; Ellinor, PT (reprint author), Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. EM ellinor@mgh.harvard.edu FU National Institutes of Health [1RO1HL092577, R01HL128914, K24HL105780]; Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme [PIOF-GA-2012-328352]; German Centre for Cardiovascular Research (DZHK) [81X2600210, 81X2600204]; American Heart Association [13EIA14220013]; Fondation Leducq [14CVD01] FX This work was supported by grants from the National Institutes of Health to P.T.E. (1RO1HL092577, R01HL128914, and K24HL105780). S.C. was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (PIOF-GA-2012-328352) and by the German Centre for Cardiovascular Research (DZHK; 81X2600210, 81X2600204). P.T.E. is also supported by an Established Investigator Award from the American Heart Association (13EIA14220013) and by the Fondation Leducq (14CVD01). NR 61 TC 4 Z9 4 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 EI 1755-3245 J9 CARDIOVASC RES JI Cardiovasc. Res. PD APR 1 PY 2016 VL 109 IS 4 BP 493 EP 501 DI 10.1093/cvr/cvv283 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DJ5KE UT WOS:000374245900005 PM 26733238 ER PT J AU Hasegawa, K Gibo, K Tsugawa, Y Shimada, YJ Camargo, CA AF Hasegawa, Kohei Gibo, Koichiro Tsugawa, Yusuke Shimada, Yuichi J. Camargo, Carlos A., Jr. TI Age-Related Differences in the Rate, Timing, and Diagnosis of 30-Day Readmissions in Hospitalized Adults With Asthma Exacerbation SO CHEST LA English DT Article DE adults; asthma exacerbation; COPD; readmission ID OBSTRUCTIVE PULMONARY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT; CHILDHOOD ASTHMA; UNITED-STATES; OLDER-ADULTS; POPULATION; INTERVENTION; OUTCOMES; PROGRAM AB BACKGROUND: Reducing hospital readmissions has attracted attention from many stake-holders. However, the characteristics of 30-day readmissions after asthma-related hospital admissions in adults are not known. It is also unclear whether older adults are at higher risk of 30-day readmission. OBJECTIVES: To investigate the rate, timing, and principal diagnosis of 30-day readmissions in adults with asthma and to determine age-related differences. METHODS: Retrospective cohort study of adults hospitalized for asthma exacerbation using the population-based inpatient samples of three states (California, Florida, and Nebraska) from 2005 through 2011. Patients were categorized into three age groups: younger (18-39 years), middle aged (40-64 years), and older (>= 65 years) adults. Outcomes were 30-day all-cause readmission rate, timing, and principal diagnosis of readmission. RESULTS: Of 301,164 asthma-related admissions at risk for 30-day readmission, readmission rate was 14.5%. Compared with younger adults, older adults had significantly higher readmission rates (10.1% vs 16.5%; OR, 2.15 [95% CI, 2.07-2.23]; P < .001). The higher rate attenuated with adjustment (OR, 1.19 [95% CI, 1.13-1.26]; P < .001), indicating that most of the age-related difference is explained by sociodemographics and comorbidities. For all age groups, readmission rate was highest in the first week after discharge and declined thereafter. Overall, only 47.1% of readmissions were assigned respiratory diagnoses (asthma, COPD, pneumonia, and respiratory failure). Older adults were more likely to present with nonrespiratory diagnoses (41.7% vs 53.8%; P < .001). CONCLUSIONS: After asthma-related admission, 14.5% of patients had 30-day readmission with wide range of principal diagnoses. Compared with younger adults, older adults had higher 30-day readmission rates and proportions of nonrespiratory diagnoses. C1 [Hasegawa, Kohei; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Shimada, Yuichi J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Gibo, Koichiro] Kurume Univ, Ctr Biostat, Kurume, Fukuoka 830, Japan. [Tsugawa, Yusuke] Harvard Univ, Dept Hlth Policy & Management, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 125 Nashua St,Ste 125, Boston, MA 02114 USA. EM khasegawa1@partners.org OI Shimada, Yuichi/0000-0002-3494-307X FU Agency for Healthcare Research and Quality (Rockville, MD) [R01HS023305] FX This study was supported by grant number R01HS023305 from the Agency for Healthcare Research and Quality (Rockville, MD). NR 38 TC 4 Z9 4 U1 2 U2 3 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2016 VL 149 IS 4 BP 1021 EP 1029 DI 10.1016/j.chest.2015.12.039 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DL2TR UT WOS:000375488600029 PM 26836926 ER PT J AU Goodman, RP Chung, DC AF Goodman, Russell P. Chung, Daniel C. TI Clinical Genetic Testing in Gastroenterology SO CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY LA English DT Review ID FAMILIAL PANCREATIC-CANCER; INFLAMMATORY-BOWEL-DISEASE; LYNCH-SYNDROME; ACMG RECOMMENDATIONS; GERMLINE MUTATIONS; RISK; POLYPOSIS; SUSCEPTIBILITY; DIAGNOSIS; GENOMICS AB Rapid advances in genetics have led to an increased understanding of the genetic determinants of human disease, including many gastrointestinal (GI) disorders. Coupled with a proliferation of genetic testing services, this has resulted in a clinical landscape where commercially available genetic tests for GI disorders are now widely available. In this review, we discuss the current status of clinical genetic testing for GI illnesses, review the available testing options, and briefly discuss indications for and practical aspects of such testing. Our goal is to familiarize the practicing gastroenterologist with this rapidly changing and important aspect of clinical care. C1 [Goodman, Russell P.; Chung, Daniel C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Chung, DC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. EM dchung@partners.org NR 53 TC 0 Z9 0 U1 4 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2155-384X J9 CLIN TRANSL GASTROEN JI Clin. Transl. Gastroenterol. PD APR PY 2016 VL 7 AR e167 DI 10.1038/ctg.2016.23 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DL5WZ UT WOS:000375709100001 PM 27124700 ER PT J AU Gelhorn, HL Kulke, MH O'Dorisio, T Yang, QM Jackson, J Jackson, S Boehm, KA Law, L Kostelec, J Auguste, P Lapuerta, P AF Gelhorn, Heather L. Kulke, Matthew H. O'Dorisio, Thomas Yang, Qi M. Jackson, Jessica Jackson, Shanna Boehm, Kristi A. Law, Linda Kostelec, Jacqueline Auguste, Priscilla Lapuerta, Pablo TI Patient-reported Symptom Experiences in Patients With Carcinoid Syndrome After Participation in a Study of Telotristat Etiprate: A Qualitative Interview Approach SO CLINICAL THERAPEUTICS LA English DT Article DE carcinoid syndrome; patient-reported; qualitative; telotristat etiprate ID CONTENT VALIDITY; OF-LIFE; OUTCOMES; TUMORS AB Purpose: Telotristat etiprate, a tryptophan hydroxylase inhibitor, was previously evaluated in a Phase II randomized, placebo-controlled clinical trial in patients with carcinoid syndrome (CS) and diarrhea not adequately controlled by octreotide. The objective of the current study was to characterize the symptom experiences of patients participating in that trial. Methods: Consenting patients participated in one-on-one, qualitative interviews focused on eliciting symptoms they had experienced in association with their CS diagnosis and recollection of symptom changes they experienced while participating in the Phase II trial. Findings: Among the 23 patients who participated in the previous 4-week dose-escalation study, 16 were eligible for interviews and 11 participated in the present study. The median time from study completion to the interview was 31 months; 4 of 11 patients were receiving telotristat etiprate in a follow-up, open-label trial at the time of interview. All of the patients (100%) described diarrhea as a symptom of CS, with effects on the emotional, social, and physical aspects of their lives. Improvement in diarrhea during the study was described by 82% of participants, and was very impactful in several patients. Results led to the design and implementation of a larger interview program in Phase III and helped to establish a definition of clinically meaningful change for the clinical development program. Implications: The diarrhea associated with CS can have a large impact on daily lives, and patient interviews can characterize and capture clinically meaningful improvements with treatment. ClinicalTrials.gov Identifier: NCT00853047. (C) 2016 The Authors. Published by Elsevier HS Journals, Inc. C1 [Gelhorn, Heather L.; Kostelec, Jacqueline; Auguste, Priscilla] Evidera, Bethesda, MD USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [O'Dorisio, Thomas] Univ Iowa Hosp & Clin, Dept Internal Med, Iowa City, IA 52242 USA. [Yang, Qi M.; Jackson, Jessica; Jackson, Shanna; Boehm, Kristi A.; Law, Linda; Lapuerta, Pablo] Lexicon Pharmaceut Inc, The Woodlands, TX USA. [Jackson, Jessica] Savara Pharmaceut, Austin, TX USA. [Law, Linda] BioHealthConsult, Cincinnati, OH USA. [Kostelec, Jacqueline] Doctor Evidence, Santa Monica, CA USA. RP Lapuerta, P (reprint author), Lexicon Pharmaceut Inc, 110 Allen Rd, Basking Ridge, NJ 07920 USA. EM PLapuerta@lexpharma.com FU Lexicon Pharmaceuticals, Inc. FX The authors thank Robin Sommers, NP, for treating patients in the telotristat etiprate study. Study was fully funded by Lexicon Pharmaceuticals, Inc. The study was designed by Lexicon Pharmaceuticals, Inc., and Dr. Gelhorn at Evidera. Evidera collected and analyzed data. Data were interpreted by Lexicon and Evidera. The manuscript was written by individual coauthors from Lexicon and Evidera and the decision to submit the paper was mutual. NR 15 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD APR PY 2016 VL 38 IS 4 BP 759 EP 768 DI 10.1016/j.clinthera.2016.03.002 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DL6FI UT WOS:000375734700010 PM 27041406 ER PT J AU Gelhorn, HL Tong, S McQuarrie, K Vernon, C Hanlon, J Maclaine, G Lenderking, W Ye, X Speck, RM Lackman, RD Bukata, SV Healey, JH Keedy, VL Anthony, SP Wagner, AJ Von Hoff, DD Singh, AS Becerra, CR Hsu, HH Lin, PS Tap, WD AF Gelhorn, Heather L. Tong, Sandra McQuarrie, Kelly Vernon, Christina Hanlon, Jennifer Maclaine, Grant Lenderking, William Ye, Xin Speck, Rebecca M. Lackman, Richard D. Bukata, Susan V. Healey, John H. Keedy, Vicki L. Anthony, Stephen P. Wagner, Andrew J. Von Hoff, Daniel D. Singh, Arun S. Becerra, Carlos R. Hsu, Henry H. Lin, Paul S. Tap, William D. TI Patient-reported Symptoms of Tenosynovial Giant Cell Tumors SO CLINICAL THERAPEUTICS LA English DT Article DE pigmented villonodular synovitis (PVNS); giant cell tumors of the tendon sheath (GCT-TS); tenosynovial giant cell tumor (TGCT); patient-reported outcomes (PRO); PROMIS ID PIGMENTED VILLONODULAR SYNOVITIS; EXPRESSION; OUTCOMES; TRANSLOCATION; INSTRUMENT; ARTHRITIS; KNEE; CSF1 AB Purpose: Tenosynovial giant cell tumor (TGCT), a rare locally aggressive neoplasm of the synovium of joints and tendon sheaths, is associated with joint destruction, inflammation, pain, and swelling, in part due to colony-stimulating factor 1 receptor bearing macrophages recruited to the tumor by genetic elevation of colony-stimulating factor 1 activity. The most common treatment is surgery, although promising pharmacologic treatments are in development. Patient-reported outcome (PRO) instruments are critical end points in demonstrating the clinical relevance of standard oncologic outcome measures and the overall impact of novel pharmacologic therapies in nonmalignant neoplastic conditions such as TGCT. The content validity of PROs relevant to patients with TGCT has not been formally investigated, and instruments to evaluate such outcomes do not exist for this condition. Methods: PRO instruments of potential relevance were evaluated by using a literature review and by clinical and PRO experts. Patients with TGCT were recruited through clinical sites and the Internet for participation in qualitative research interviews to identify predominant symptoms and to test the relevance and content validity of several PRO measures. Select PRO measures were included in a Phase I clinical trial, and preliminary results of the PRO end points are reported descriptively. Findings: Of the 22 subjects who participated in qualitative interviews, 73% were female, and their mean age was 42.5 years (range, 27-56 years). The TGCTs (19 diffuse and 3 localized) were located in the knee (n = 15), hip (n = 3), ankle (n = 2), elbow (n = 1), and forearm (n = 1). The most common symptoms cited were pain (82%), swelling (86%), stiffness (73%), reduced range of motion (64%), and joint instability (64%), which were consistent with clinical expert input and with the content of instruments chosen by PRO experts. The worst pain numeric rating scale, Patient Reported Outcomes Measurement Information System physical functioning items, and the Western Ontario and McMaster Universities Osteoarthritis Index, as well as a worst stiffness numeric rating scale developed for TGC1, were confirmed as meaningful measures of TGCT patient symptoms and were well understood in qualitative interviews. Results from the Phase I trial showed trends of improvement in both pain and stiffness over time. Implications: This study is the first to gather information directly from patients with TGCT regarding their symptom experiences. Pain, stiffness, and physical functioning are important treatment outcomes in patients with TGCT. We have identified content-valid PRO measures of these concepts, which are included in an ongoing Phase III TGCT clinical trial with pexidartinib (PLX3397) (NCT02371369). (C) 2016 The Authors. Published by Elsevier HS Journals, Inc. C1 [Gelhorn, Heather L.; McQuarrie, Kelly; Vernon, Christina; Hanlon, Jennifer; Lenderking, William; Speck, Rebecca M.] Evidera, 7101 Wisconsin Ave,Suite 1400, Bethesda, MD 20814 USA. [Tong, Sandra; Hsu, Henry H.; Lin, Paul S.] Plexxikon Inc, Berkeley, CA USA. [Maclaine, Grant] Daiichi Sankyo Dev Ltd, Gerrards Cross, Bucks, England. [Ye, Xin] Daiichi Sankyo Pharma Dev, Edison, NJ USA. [Lackman, Richard D.] Cooper Univ, Ctr Hlth, Orthopaed Oncol Ctr, Camden, NJ USA. [Bukata, Susan V.; Singh, Arun S.] Ronal Reagan UCLA Med Ctr, Los Angeles, CA USA. [Healey, John H.; Tap, William D.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Healey, John H.; Tap, William D.] Weill Cornell Med Coll, New York, NY USA. [Keedy, Vicki L.] Vanderbilt Univ, Med Ctr, Hematol Oncol, Nashville, TN USA. [Anthony, Stephen P.] Texas Oncol Tyler, Tyler, TX USA. [Wagner, Andrew J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Von Hoff, Daniel D.] HonorHlth & Translat Genom Res Inst, Scottsdale, AZ USA. [Becerra, Carlos R.] Sammons Canc Ctr US Oncol, Dallas, TX USA. RP Gelhorn, HL (reprint author), Evidera, 7101 Wisconsin Ave,Suite 1400, Bethesda, MD 20814 USA. EM heather.gelhorn@evidera.com FU Daiichi Sankyo Development Ltd; Plexxikon Inc; Zymeworks Biopharmaceuticals; Plexxikon; Daiichi Sankyo Development Ltd.; Five Prime Therapeutics FX G. Maclaine and X. Ye are employees of Daiichi Sankyo Development Ltd, which provided financial support for this research. S. Tong and P. Lin are employees of Plexxikon Inc, which provided financial support for this research. J.H. Healey is a paid consultant of Daiichi Sankyo Development Ltd. H. Hsu is a paid consultant of Plexxikon Inc. S. Anthony is a paid member of the Paradigm Medical Evidence Team and a paid consultant of Zymeworks Biopharmaceuticals. W. Taq is a paid consultant of Plexxikon and Daiichi Sankyo Development Ltd. The institutions of S. Bukata, D. Von Hoff, and V. Keedy received funding from Plexxikon for conducting the study for this work. D. Von Hoff is a paid consultant of Five Prime Therapeutics. H. Gelhom, K. McQuarrie, C. Vernon, J. Hanlon, W. Lenderking, and R. Speck participated in this project as employees of Evidera, a company which performs work for hire for multiple pharmaceutical and device companies in outcomes research. K. McQuarrie is currently employed by Janssen. A. Wagner, A. Singh, C. Becerra, J. Hanlon, and R. Lackman have no conflicts of interest related to this work to report. NR 25 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD APR PY 2016 VL 38 IS 4 BP 778 EP 793 DI 10.1016/j.clinthera.2016.03.008 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DL6FI UT WOS:000375734700012 PM 27041409 ER PT J AU Fei, HW Ali, MT Tan, TC Cheng, KH Salama, L Hua, LQ Zeng, X Halpern, EF Taghian, A MacDonald, SM Scherrer-Crosbie, M AF Fei, Hong-wen Ali, Mohammed T. Tan, Timothy C. Cheng, Kai-Hung Salama, Laura Hua, Lanqi Zeng, Xin Halpern, Elkan F. Taghian, Alphonse MacDonald, Shannon M. Scherrer-Crosbie, Marielle TI Left Ventricular Global Longitudinal Strain in HER-2+Breast Cancer Patients Treated with Anthracyclines and Trastuzumab Who Develop Cardiotoxicity Is Associated with Subsequent Recovery of Left Ventricular Ejection Fraction SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE cardiotoxicity; chemotherapy; echocardiography; global longitudinal strain ID BREAST-CANCER; HEART-FAILURE; MYOCARDIAL-INFARCTION; DEFORMATION INDEXES; ADJUVANT THERAPY; ECHOCARDIOGRAPHY; CARDIOMYOPATHY; CHEMOTHERAPY; SURVIVAL; TRIAL AB AimThe combination of anthracyclines (AC) and trastuzumab (TRZ) is highly effective in patients with aggressive HER-2 + breast cancer, but has a significant risk of cardiotoxicity (CT). Trastuzumab-induced CT may be reversible. The aim of this study was to identify echocardiographic parameters associated with recovery of left ventricular ejection fraction (LVEF) in patients who developed CT after AC and TRZ treatment. Methods and ResultsWomen with newly diagnosed breast cancer treated with AC followed by TRZ and monitored with serial echocardiograms were retrospectively studied. Left ventricular end-diastolic and systolic volumes, LVEF, and global longitudinal strain (GLS) were examined. Development and reversibility of CT were defined based on changes in LVEF according to the 2014 ASE/EACVI recommendations. Cox analysis was used to determine the association of echocardiographic variables with the subsequent development and reversibility of CT. Ninety-five patients underwent 5 echocardiograms or more in a 17-month (13-28 months) follow-up period. Nineteen patients (20%) developed CT. Left ventricular volumes, LVEF, and GLS measured after AC completion identified the subsequent development of CT. Of the 19 patients with CT, the LVEF partially or fully recovered in 13 (68%). GLS at the time of CT diagnosis was associated with subsequent recovery of LVEF (P = 0.004). ConclusionIn patients with breast cancer treated with AC and TRZ who develop CT, GLS at the time of CT diagnosis is associated with subsequent recovery of LVEF and may be useful for risk stratification and to guide treatment. C1 [Fei, Hong-wen; Ali, Mohammed T.; Cheng, Kai-Hung; Hua, Lanqi; Zeng, Xin; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Fei, Hong-wen; Ali, Mohammed T.; Cheng, Kai-Hung; Salama, Laura; Hua, Lanqi; Zeng, Xin; Halpern, Elkan F.; Taghian, Alphonse; MacDonald, Shannon M.; Scherrer-Crosbie, Marielle] Harvard Univ, Sch Med, Boston, MA USA. [Fei, Hong-wen] Guangdong Gen Hosp, Guangdong Prov Cardiovasc Inst, Div Adult Echocardiog, Guangzhou, Guangdong, Peoples R China. [Fei, Hong-wen] Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China. [Tan, Timothy C.] Univ Western Sydney, Blacktown Clin Sch, Dept Cardiol, Fac Med, Sydney, NSW, Australia. [Tan, Timothy C.] Univ New S Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia. [Salama, Laura; Taghian, Alphonse; MacDonald, Shannon M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com NR 29 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-2822 EI 1540-8175 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD APR PY 2016 VL 33 IS 4 BP 519 EP 526 DI 10.1111/echo.13168 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK2QX UT WOS:000374760600003 PM 26992012 ER PT J AU Viana-Huete, V Guillen, C Garcia-Aguilar, A Garcia, G Fernandez, S Kahn, CR Benito, M AF Viana-Huete, Vanesa Guillen, Carlos Garcia-Aguilar, Ana Garcia, Gema Fernandez, Silvia Kahn, C. R. Benito, Manuel TI Essential Role of IGFIR in the Onset of Male Brown Fat Thermogenic Function: Regulation of Glucose Homeostasis by Differential Organ-Specific Insulin Sensitivity SO ENDOCRINOLOGY LA English DT Article ID ADIPOSE-TISSUE; SKELETAL-MUSCLE; ACID OXIDATION; ADULT HUMANS; RECEPTOR; RESISTANCE; ADIPOCYTES; ABLATION; OBESITY; MICE AB Brown fat is a thermogenic tissue that generates heat to maintain body temperature in cold environments and dissipate excess energy in response to overfeeding. We have addressed the role of the IGFIR in the brown fat development and function. Mice lacking IGFIR exhibited normal brown adipose tissue/body weight in knockout (KO) vs control mice. However, lack of IGFIR decreased uncoupling protein 1 expression in interscapular brown fat and beige cells in inguinal fat. More importantly, the lack of IGFIR resulted in an impaired cold acclimation. No differences in the total fat volume were found in the KO vs control mice. Epididymal fat showed larger adipocytes but with a lower number of adipocytes in KO vs control mice at age 12 months. In addition, KO mice showed a sustained moderate hyperinsulinemia and hypertriglyceridemia upon time and hepatic insulin insensitivity associated with lipid accumulation, with the outcome of a global insulin resistance. In addition, we found that the expression of uncoupling protein 3 in the skeletal muscle was decreased and its expression was increased in the heart in parallel with the expression of beta-2 adrenergic receptors. Upon nonobesogenic high-fat diet, we found a severe insulin resistance in the liver and in the skeletal muscle, but unchanged insulin sensitivity in the heart. In conclusion, our data suggest that IGFIR it is not an essential growth factor in the brown fat development in the presence of the IR and very high plasma levels of IGF-I, but it is indispensable for full brown fat functionality. C1 [Viana-Huete, Vanesa; Guillen, Carlos; Garcia-Aguilar, Ana; Garcia, Gema; Fernandez, Silvia; Benito, Manuel] Univ Complutense Madrid, Biol Fac Pharm, Dept Biochem & Mol Biol, E-28040 Madrid, Spain. [Viana-Huete, Vanesa; Guillen, Carlos; Garcia-Aguilar, Ana; Garcia, Gema; Fernandez, Silvia; Benito, Manuel] Inst Hlth Carlos III, Spanish Diabet & Metab Res Network, Madrid 28029, Spain. [Kahn, C. R.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Benito, M (reprint author), Univ Complutense Madrid, Dept Biochem & Mol Biol, Sch Pharm, E-28040 Madrid, Spain. EM mbenito@ucm.es RI Garcia-Aguilar, Ana/A-5172-2017; Guillen, Carlos/J-9728-2014 OI Garcia-Aguilar, Ana/0000-0003-1648-7143; Guillen, Carlos/0000-0002-9370-6314 FU Ministerio de Ciencia e Innovacion [SAF2008/00031, SAF2011/22555]; CIBER de Diabetes y Enfermedades Metabolicas Asociadas; Spanish Diabetes and Metabolic Research Network; Instituto de Salud Carlos III, Spain FX This work was supported by Grants SAF2008/00031 and SAF2011/22555 from Ministerio de Ciencia e Innovacion, and CIBER de Diabetes y Enfermedades Metabolicas Asociadas, Spanish Diabetes and Metabolic Research Network, Instituto de Salud Carlos III, Spain. NR 35 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2016 VL 157 IS 4 BP 1495 EP 1511 DI 10.1210/en.2015-1623 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DK0CK UT WOS:000374579800019 PM 26910308 ER PT J AU Kadayifci, A Al-Haddad, M Atar, M Dewitt, JM Forcione, DG Sherman, S Casey, BW Fernandez-del Castillo, C Schmidt, CM Pitman, MB Brugge, WR AF Kadayifci, Abdurrahman Al-Haddad, Mohammad Atar, Mustafa Dewitt, John M. Forcione, David G. Sherman, Stuart Casey, Brenna W. Fernandez-del Castillo, Carlos Schmidt, C. Max Pitman, Martha B. Brugge, William R. TI The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts SO ENDOSCOPY INTERNATIONAL OPEN LA English DT Article ID INTERNATIONAL CONSENSUS GUIDELINES; MOLECULAR ANALYSIS; FLUID; NEOPLASMS; MANAGEMENT; PATHOLOGY; LESIONS AB Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100% and 93.2%), but low sensitivity (48.3% and 56.3%) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8%) and AUC (0.84) significantly compared to KRAS (65.3% and 0.74) or CEA (65.8% and 0.74) alone, but only in the clinical cohort (P<0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73% vs. 37%, P=0.001). The negative predictive value of KRAS mutation was 77.6% in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use. C1 [Kadayifci, Abdurrahman; Atar, Mustafa; Forcione, David G.; Casey, Brenna W.; Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. [Kadayifci, Abdurrahman] Gaziantep Univ, Div Gastroenterol, Sch Med, Gaziantep, Turkey. [Al-Haddad, Mohammad; Dewitt, John M.; Sherman, Stuart] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. [Al-Haddad, Mohammad] Cleveland Clin, Ctr Digest Dis, Abu Dhabi, U Arab Emirates. [Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Schmidt, C. Max] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Pitman, Martha B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Kadayifci, A (reprint author), 3H GI Associates, Blossom St Massachusetts Gen Hosp, Zero Emerson Pl, Boston, MA 02114 USA. EM akadayifci@mgh.harvard.edu NR 26 TC 4 Z9 4 U1 2 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 2364-3722 EI 2196-9736 J9 ENDOSC INT OPEN JI Endosc. Int. Open PD APR PY 2016 VL 4 IS 4 BP E391 EP E396 DI 10.1055/s-0042-101755 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DK1PZ UT WOS:000374686800003 PM 27092317 ER PT J AU Srivastava, A Kay, MA Athanasopoulos, T Angastiniotis, M Anagnostopoulos, A Karponi, G Yannaki, E Zon, LI Lederer, CW Phylactides, MS Kleanthous, M AF Srivastava, Arun Kay, Mark A. Athanasopoulos, Takis Angastiniotis, Michael Anagnostopoulos, Achilles Karponi, Garyfalia Yannaki, Evangelia Zon, Leonard I. Lederer, Carsten W. Phylactides, Marios S. Kleanthous, Marina TI A Tribute to George Stamatoyannopoulos SO HUMAN GENE THERAPY LA English DT Biographical-Item C1 [Srivastava, Arun] Univ Florida, Coll Med, Div Cellular & Mol Therapy, Dept Pediat Mol Genet & Microbiol,Powell Gene The, Canc & Genet Res Complex,2033 Mowry Rd, Gainesville, FL 32611 USA. [Kay, Mark A.] Stanford Univ, Dept Pediat & Genet, Stanford, CA 94305 USA. [Athanasopoulos, Takis] Univ Wolverhampton UoW, Fac Sci & Engn, Mol Biotechnol, City Campus South,MA Bldg,Room MA206, Wolverhampton WV1 1LY, W Midlands, England. [Angastiniotis, Michael] Thalassaemia Int Federat, POB 28807, CY-2083 Strovolos, Cyprus. [Anagnostopoulos, Achilles] Hellen Soc Gene Therapy & Regenerat Med, Thessaloniki 57010, Greece. [Anagnostopoulos, Achilles] George Papanicolaou Hosp, Publ Cord Blood Bank, Gene & Cell Therapy Ctr, Haematol Dept,BMT Unit, Thessaloniki 57010, Greece. [Karponi, Garyfalia] George Papanicolaou Hosp, Hematol BMT Unit, Gene & Cell Therapy Ctr, Thessaloniki, Greece. [Yannaki, Evangelia] Univ Washington, Seattle, WA 98195 USA. [Yannaki, Evangelia] G Papanicolaou Hosp, Hematol Dpt BMT Unit, Gene & Cell Therapy Ctr, Thessaloniki 57010, Greece. [Zon, Leonard I.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Chem Biol Program, Cambridge, MA 02138 USA. [Lederer, Carsten W.; Phylactides, Marios S.; Kleanthous, Marina] Cyprus Inst Neurol & Genet, Mol Genet Thalassaemia Dept, 6 Int Airport Ave, CY-1683 Nicosia, Cyprus. RP Zon, LI (reprint author), Karp Res Bldg,7th Floor,300 Longwood Ave, Boston, MA 02115 USA.; Zon, LI (reprint author), Cyprus Inst Neurol & Genet, Mol Genet Thalassaemia Dept, 6 Int Airport Ave, CY-1683 Nicosia, Cyprus. EM aruns@peds.ufl.edu; markay@stanford.edu; t.athanasopoulos@wlv.ac.uk; thalassaemia@cytanet.com.cy; achanagh@gmail.com; aminoxy@yahoo.gr; eyannaki@u.washington.edu; zon@enders.tch.harvard.edu; Lederer@cing.ac.cy OI Anagnostopoulos, Achilles/0000-0003-4384-9031 NR 1 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 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD APR PY 2016 VL 27 IS 4 BP 280 EP 286 DI 10.1089/hum.2016.29025.gst PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA DK1CD UT WOS:000374649200002 PM 27074151 ER PT J AU Avagyan, S Zon, LI AF Avagyan, Serine Zon, Leonard I. TI Fish to Learn: Insights into Blood Development and Blood Disorders from Zebrafish Hematopoiesis SO HUMAN GENE THERAPY LA English DT Review ID RIBOSOMAL-PROTEIN S19; STEM-CELLS; EMBRYONIC HEMATOPOIESIS; STEM/PROGENITOR CELLS; TRANSGENIC ZEBRAFISH; AORTIC ENDOTHELIUM; GENE DISRUPTION; ADULT ZEBRAFISH; IRON OVERLOAD; IDENTIFICATION AB Since its introduction in early 1980s, the zebrafish (Danio rerio) has become an invaluable vertebrate animal model system to study many human disorders in almost all systems, from hepatic and brain pathology, to autoimmune and psychiatric disorders. Hematopoiesis between zebrafish and mammals is highly conserved, making the zebrafish an attractive model to study hematopoietic development and blood disorders. Unique attributes of the zebrafish include the ability to perform large-scale genetic and chemical screens in vivo, study development at the cellular level, and use transgenic fish to dissect mechanisms of disease or drug effects. This review summarizes major discoveries that helped define molecular control of hematopoiesis in vertebrates and specific contributions from studies in zebrafish. C1 [Avagyan, Serine; Zon, Leonard I.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Avagyan, Serine; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Chem Biol Program, Cambridge, MA 02138 USA. RP Zon, LI (reprint author), Boston Childrens Hosp, Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02215 USA. EM zon@enders.tch.harvard.edu FU Potter Fellowship; Abraham Fellowship from Dana-Farber/Boston Children's Cancer and Blood Disorders Center FX S.A. is a recipient of the Potter Fellowship and the Abraham Fellowship from Dana-Farber/Boston Children's Cancer and Blood Disorders Center. NR 65 TC 2 Z9 2 U1 4 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD APR PY 2016 VL 27 IS 4 BP 287 EP 294 DI 10.1089/hum.2016.024 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA DK1CD UT WOS:000374649200003 PM 27018965 ER PT J AU Weissman, RS Becker, AE Bulik, CM Frank, GKW Klump, KL Steiger, H Strober, M Thomas, J Waller, G Walsh, BT AF Weissman, Ruth S. Becker, Anne E. Bulik, Cynthia M. Frank, Guido K. W. Klump, Kelly L. Steiger, Howard Strober, Michael Thomas, Jennifer Waller, Glenn Walsh, B. Timothy TI Speaking of That: Terms to Avoid or Reconsider in the Eating Disorders Field SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE eating disorders; anorexia nervosa; bulimia nervosa; binge-eating disorder; binge eating; subthreshold eating disorder; subclinical eating disorder; anorexic; bulimic; anorexia ID ANOREXIA-NERVOSA; EXAMINATION-QUESTIONNAIRE; BULIMIA-NERVOSA; WOMEN; ADOLESCENTS; ATTITUDES; VALIDITY; THERAPY AB Inspired by an article on 50 terms that, in the interest of clarity in scientific reasoning and communication in psychology, psychiatry, and allied fields, should be avoided or at most be used sparingly and only with explicit caveats,(1) we propose a list of terms to avoid or think twice about before using when writing for the International Journal of Eating Disorders (IJED). Drawing upon our experience as reviewers or editors for the IJED, we generated an abridged list of such terms. For each term, we explain why it made our list and what alternatives we recommend. We hope that our list will contribute to improved clarity in scientific thinking about eating disorders, and that it will stimulate discussion of terms that may need to be reconsidered in our field's vocabulary to ensure the use of language that is respectful and sensitive to individuals who experience an eating disorder. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:349-353) C1 [Weissman, Ruth S.] Wesleyan Univ, Dept Psychol, 207 High St, Middletown, CT 06459 USA. [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Becker, Anne E.; Thomas, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Becker, Anne E.; Thomas, Jennifer] Harvard Univ, Sch Med, Dept Psychiat, Eating Disorders Clin & Res Program, Boston, MA 02115 USA. [Bulik, Cynthia M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Bulik, Cynthia M.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Bulik, Cynthia M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Frank, Guido K. W.] Univ Colorado Denver, Dept Psychiat, Denver, CO USA. [Frank, Guido K. W.] Univ Colorado Denver, Dept Neurosci, Denver, CO USA. [Klump, Kelly L.] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. [Steiger, Howard] McGill Univ, Douglas Univ Inst, Montreal, PQ, Canada. [Steiger, Howard] McGill Univ, Dept Psychiat, Eating Disorders Continuum, Montreal, PQ, Canada. [Strober, Michael] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Jane & Terry Semel Inst Neurosci & Human Behav, Stewart & Lynda Resnick Neuropsychiat Hosp,David, Los Angeles, CA 90024 USA. [Waller, Glenn] Univ Sheffield, Dept Psychol, Sheffield S10 2TN, S Yorkshire, England. [Walsh, B. Timothy] Columbia Univ, New York State Psychiat Inst, New York, NY USA. [Walsh, B. Timothy] Columbia Univ, Dept Psychiat, New York, NY USA. RP Weissman, RS (reprint author), Wesleyan Univ, Dept Psychol, 207 High St, Middletown, CT 06459 USA. EM rweissman@wesleyan.edu OI Frank, Guido/0000-0002-6590-3441 FU Shire Pharmaceuticals; Global Foundation for Eating Disorders FX Dr. Bulik is a grant recipient from Shire Pharmaceuticals, and has consulted for Ironshore, and receives royalties from Pearson. Drs. Frank, Klump, Thomas, Waller, and Weissman receive an annual honorarium from John Wiley & Sons for their role as associate editors and editor-in-chief. Dr. Walsh receives research support from the Global Foundation for Eating Disorders and honoraria from Guilford Press, McGraw-Hill, and Wolters Kluwer. NR 33 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD APR PY 2016 VL 49 IS 4 BP 349 EP 353 DI 10.1002/eat.22528 PG 5 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA DJ8SC UT WOS:000374482000001 PM 27084795 ER PT J AU Bourguignon, LYW AF Bourguignon, Lilly Y. W. TI Matrix Hyaluronan Promotes Specific MicroRNA Upregulation Leading to Drug Resistance and Tumor Progression SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE hyaluronan (HA); CD44; microRNA (miRNA); cancer stem cells (CSCs); signaling; chemoresistance; tumor progression ID BREAST-CANCER CELLS; EMBRYONIC STEM-CELLS; CYTOSKELETON ACTIVATION; HOMING RECEPTOR; MARKER NANOG; ACID BINDING; EXPRESSION; CD44; INVASION; METASTASIS AB Solid tumor invasion, metastasis and therapeutic drug resistance are the common causes for serious morbidity and cancer recurrence in patients. A number of research studies have searched for malignancy-related biomarkers and drug targets that are closely linked to tumor cell properties. One of the candidates is matrix hyaluronan (HA), which is known as one of the major extracellular matrix (ECM) components. HA serves as a physiological ligand for surface CD44 molecule and also functions as a bio-regulator. The binding of HA to CD44 has been shown to stimulate concomitant activation of a number of oncogenic pathways and abnormal cellular processes in cancer cells and cancer stem cells (CSCs). MicroRNAs (miRNAs) belong to a class of small RNAs containing similar to 20-25 nucleotides and are known to promote aberrant cellular functions in cancer cells. In this article, I have focused on the role of HA interaction with CD44 and several important signaling molecules in the regulation of unique miRNAs (e. g., miR-21, miR-302 and miR-10b) and their downstream targets leading to multiple tumor cell-specific functions (e. g., tumor cell growth, drug resistance and metastasis) and cancer progression. This new knowledge could provide the groundwork necessary for establishing new tumor markers and developing important, novel drugs targeted against HA/CD44-associated tumor progression, which can be utilized in the therapeutic treatment of metastatic cancer patients. C1 [Bourguignon, Lilly Y. W.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, 4150 Clement St, San Francisco, CA 94121 USA. [Bourguignon, Lilly Y. W.] Endocrine Unit 111N2, 4150 Clement St, San Francisco, CA 94121 USA. RP Bourguignon, LYW (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, 4150 Clement St, San Francisco, CA 94121 USA.; Bourguignon, LYW (reprint author), Endocrine Unit 111N2, 4150 Clement St, San Francisco, CA 94121 USA. EM lilly.bourguignon@ucsf.edu OI Bourguignon, Lilly/0000-0003-3172-9251 FU Veterans Affairs (VA) Merit Review Awards [RR & D-1I01 RX000601, BLR & D-5I01 BX000628]; United States Public Health [R01 CA66163]; DOD (Department of Defense) FX This work was supported by Veterans Affairs (VA) Merit Review Awards (RR & D-1I01 RX000601 and BLR & D-5I01 BX000628), United States Public Health grants (R01 CA66163) and DOD (Department of Defense) grant Lilly Y.W. Bourguignon is a VA Senior Research Career Scientist. NR 65 TC 2 Z9 2 U1 3 U2 10 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD APR PY 2016 VL 17 IS 4 AR 517 DI 10.3390/ijms17040517 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA DK0EL UT WOS:000374585300096 PM 27070574 ER PT J AU Galindo, J Fadlallah, A Robinson, S Chelala, E Melki, SA AF Galindo, Joanna Fadlallah, Ali Robinson, Steve Chelala, Elias Melki, Samir A. TI Risk factors for loss of epithelial flap integrity in laser-assisted subepithelial keratectomy surgery SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID PHOTOREFRACTIVE KERATECTOMY; KERATOMILEUSIS; MYOPIA; OUTCOMES; ALCOHOL; CORNEA AB PURPOSE: To evaluate risk factors leading to loss of epithelial flap integrity in laser-assisted subepithelial keratectomy (LASEK). SETTING: Boston Eye Group, Brookline, Massachusetts, USA. DESIGN: Retrospective case study. METHODS: This retrospective chart review was performed for LASEK surgeries that occurred between January 2009 and October 2013. Logistic regression was performed to determine whether epithelium preservation was correlated with age, sex, sphere, cylinder, spherical equivalent (SE), keratometry, and central corneal thickness (CCT). RESULTS: The study reviewed 1009 eyes of 509 patients with a mean age of 29.1 years +/- 12.2 (SD). The mean preoperative spherical refraction was -4.7 +/- 2.5 diopters (D), and the mean preoperative cylinder was -1.1 +/- 0.8 D. The mean preoperative decimal corrected distance visual acuity was 1.01 +/- 0.07. Single-sheet mobilization of the loosened epithelium flap was found in 72.3% of cases. Fragmented preservation events occurred in 17.6% of cases; the flap was discarded in 10.0% of cases. Epithelium preservation was significantly correlated with age (P = .048) but not with other parameters (P > .05 for sex, sphere, cylinder, SE, keratometry, CCT, and surgeon experience). Epithelial flap dissection was less likely to lead to a single epithelial sheet in patients older than 50 years than in younger patients (56.3% versus 74.9%). The mean postoperative decimal uncorrected distance visual acuity (UDVA) at 3 months was 0.98 +/- 0.08. There was no statistical difference in postoperative UDVA between the undiscarded flap group and discarded flap group (P = .128). CONCLUSION: Successful dissection of single-sheet epithelial flap diminished with age. (C) 2016 ASCRS and ESCRS C1 [Galindo, Joanna; Fadlallah, Ali; Robinson, Steve; Melki, Samir A.] Harvard Univ, Sch Med, Boston Eye Grp, Boston, MA USA. [Fadlallah, Ali; Melki, Samir A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Chelala, Elias] St Joseph Univ, Fac Med, Beirut, Lebanon. RP Melki, SA (reprint author), Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM samir_melki@meei.harvard.edu NR 17 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 EI 1873-4502 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD APR PY 2016 VL 42 IS 4 BP 591 EP 595 DI 10.1016/j.jcrs.2016.01.039 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DL3DW UT WOS:000375515400014 PM 27113883 ER PT J AU Aaronson, E Benzer, T Borczuk, P AF Aaronson, Emily Benzer, Theodore Borczuk, Pierre TI SEVENTY-TWO-HOUR RETURNS ARE NOT USEFUL IN IDENTIFYING EMERGENCY DEPARTMENT PATIENTS WITH A CONCERNING INTRA-ABDOMINAL PROCESS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency medicine; health care safety; health care quality; performance measures; quality assessment; quality measurement ID QUALITY; CARE; REVISITS; VISITS; TIME; PAIN AB Background: Seventy-two-hour returns to the emergency department (ED) have been used to identify patients who are believed to have been more likely to have suffered medical errors, missed diagnoses, or failure or inadequacy of previous treatment or discharge planning. This approach has been criticized as arbitrary, however, citing the lack of evidence to support its homogenous application to all organ system-based complaints and the unclear implication of returns. Objective: Given the significant burden of gastrointestinal (GI)-related illness, our objective was to determine if an audit of 72-hour returns of GI-related diagnoses appropriately captures patients who return with a concerning diagnosis (CD) on their second visit. Methods: Ten emergency physicians were surveyed and a list of concerning, "not to be missed'' diagnoses were generated. The demographic and clinical variables were collected and analyzed on all patients with a GI International Classification of Diseases, 9th revision code presenting to an urban, university-affiliated ED between July 2013 and March 2014. Results: There were 10,012 patient visits during the study period, including 1006 patients (10%) with >= 1 return visits. One hundred forty-seven patients (15%) returned within 72 hours, and 859 patients (85%) returned in > 72 hours. Patients that returned within 72 hours were no more likely to have a CD than those that returned at a later time (13.6% vs. 14.4%; p = 0.79). Conclusion: An audit of 72-hour returns only captures a small percentage of patients that return with a CD, and these patients are at no greater risk of harboring a CD than those that return at a later date. (C) 2016 Elsevier Inc. C1 [Aaronson, Emily; Benzer, Theodore; Borczuk, Pierre] Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Ste 3B, Boston, MA 02114 USA. [Aaronson, Emily; Benzer, Theodore; Borczuk, Pierre] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Aaronson, Emily; Benzer, Theodore; Borczuk, Pierre] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. RP Aaronson, E (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Ste 3B, Boston, MA 02114 USA. OI Borczuk, Pierre/0000-0002-6242-7312 NR 25 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD APR PY 2016 VL 50 IS 4 BP 560 EP 566 DI 10.1016/j.jemermed.2015.11.015 PG 7 WC Emergency Medicine SC Emergency Medicine GA DI2CH UT WOS:000373302800010 PM 27016953 ER PT J AU Kinnaman, KA Kimberly, HH Pivetta, E Platz, E Chudgar, A Adduci, A Stone, MB Rempell, JS AF Kinnaman, Karen A. Kimberly, Heidi H. Pivetta, Emanuele Platz, Elke Chudgar, Avni Adduci, Alexander Stone, Michael B. Rempell, Joshua S. TI EVALUATION OF THE AORTIC ARCH FROM THE SUPRASTERNAL NOTCH VIEW USING FOCUSED CARDIAC ULTRASOUND SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE ultrasound; cardiac; aorta ID AMERICAN SOCIETY; TRANSTHORACIC ECHOCARDIOGRAPHY; ADULTS AB Background: The suprasternal notch view (SSNV) is an additional echocardiographic view not routinely used by emergency physicians (EPs) performing focused cardiac ultrasound (FOCUS). Objective: This pilot study determined the ease and self-perceived accuracy of the SSNV as performed by EPs. Additionally, we assessed the accuracy of FOCUS including the SSNV in thoracic aortic measurements compared to chest CT angiography (CTA). Methods: This was a prospective, observational, pilot study of adult patients undergoing chest CTA. Thoracic aortic measurements were recorded at the sinus of Valsalva, sinotubular junction, and ascending aorta at its widest diameter in the parasternal long axis (PSL) view and SSNV. EPs rated ease of acquisition and self-perceived accuracy of thoracic aorta measurements. Two blinded radiologists performed thoracic aortic CTA measurements at predefined locations corresponding to the ultrasound measurements. Results: Of the 79 patients (median age 57 years) enrolled, the SSNV was obtained in 97% of cases. EPs rated the ease of obtaining the SSNV as "easy'' in 64.5% of cases and "very difficult'' in 7.6% of cases. The mean difference between ultrasound (FOCUS plus SSNV) and CTA measurements were 1.2 mm (95% limits of agreement -2.9 to 5.3) at the sinus of Valsalva, 1.0 mm (95% limits of agreement -5.5 to 3.6 mm) at the sinotubular junction, 0.8 mm (95% limits of agreement -6.2 to 4.6 mm) at the proximal ascending aorta, and 0.6 mm (95% limits of agreement -2.8 to 4.0) at the aortic arch. Conclusions: Our findings suggest that the SSNV is an easily attainable and accurate view of the thoracic aorta that can be obtained by EPs in the majority of ED patients. (C) 2016 Elsevier Inc. C1 [Kinnaman, Karen A.; Kimberly, Heidi H.; Pivetta, Emanuele; Platz, Elke; Stone, Michael B.; Rempell, Joshua S.] Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. [Kinnaman, Karen A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Kinnaman, Karen A.; Kimberly, Heidi H.; Platz, Elke; Stone, Michael B.; Rempell, Joshua S.] Harvard Affiliated Emergency Med Residency, Boston, MA USA. [Chudgar, Avni; Adduci, Alexander] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. RP Kinnaman, KA (reprint author), 81 Highland Ave, Salem, MA 01970 USA. OI Pivetta, Emanuele/0000-0003-1446-1169 FU National Heart, Lung and Blood Institute [1K23HL123533-01A1] FX The authors would like to thank Dr. Jose Rivero, chief sonographer of the Non-Invasive Cardiac Imaging Laboratory at Brigham and Women's Hospital in Boston for his assistance with the initial investigator training for this study. The writing of this manuscript was supported by a grant from the National Heart, Lung and Blood Institute [grant number 1K23HL123533-01A1] (EP). NR 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD APR PY 2016 VL 50 IS 4 BP 643 EP + DI 10.1016/j.jemermed.2015.12.002 PG 9 WC Emergency Medicine SC Emergency Medicine GA DI2CH UT WOS:000373302800020 PM 26830361 ER PT J AU Ardehali, A Warnecke, G Van Raemdonck, D Loor, G Kukreja, J Smith, M Rea, F Massard, G De Robertis, F Nagendran, J Moradiellos, J Dhital, K Knosalla, C Bermudez, C Tsui, S Wang, I McCurry, K Deuse, T Thomas, P Sommer, W Wiegmann, B Tudorache, I Khun, C Avsar, M Schiavon, M Santelmo, N Olland, A Falcoz, P Varela, A Simon, A Reichenspurner, H Haverich, A Madsen, J Hertz, M AF Ardehali, A. Warnecke, G. Van Raemdonck, D. Loor, G. Kukreja, J. Smith, M. Rea, F. Massard, G. De Robertis, F. Nagendran, J. Moradiellos, J. Dhital, K. Knosalla, C. Bermudez, C. Tsui, S. Wang, I. McCurry, K. Deuse, T. Thomas, P. Sommer, W. Wiegmann, B. Tudorache, I. Khun, C. Avsar, M. Schiavon, M. Santelmo, N. Olland, A. Falcoz, P. Varela, A. Simon, A. Reichenspurner, H. Haverich, A. Madsen, J. Hertz, M. TI Impact of OCS Lung Portable EVLP on Pulmonary Function and Bronchiolitis Obliterans in Standard Lung Transplant Recipients - Prospective Evidence from the OCS Lung INSPIRE Trial Patients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Ardehali, A.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Warnecke, G.; Sommer, W.; Wiegmann, B.; Tudorache, I.; Khun, C.; Avsar, M.; Haverich, A.] Hannover Med Sch, Hannover, Germany. [Van Raemdonck, D.] Leuven Univ Hosp, Leuven, Belgium. [Loor, G.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Kukreja, J.] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA. [Smith, M.] St Josephs Med Ctr, Phoenix, AZ USA. [Rea, F.; Schiavon, M.] Univ Padua Hosp, Padua, Italy. [Massard, G.; Santelmo, N.; Olland, A.; Falcoz, P.] Strasbourg Univ Hosp, Strasbourg, France. [De Robertis, F.; Simon, A.] Harefield Hosp, London, England. [Nagendran, J.] Univ Alberta, Med Ctr, Edmonton, ON, Canada. [Moradiellos, J.; Varela, A.] Univ Puerta de Hierro Hosp, Madrid, Spain. [Dhital, K.] St Vincents Hosp, Sydney, NSW 2010, Australia. [Knosalla, C.] German Heart Inst, Berlin, Germany. [Bermudez, C.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Tsui, S.] Papworth Hosp, Cambridge CB3 8RE, England. [Wang, I.] Indiana Univ, Med Ctr, Indianapolis, IN USA. [McCurry, K.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Deuse, T.; Reichenspurner, H.] Univ Hamburg Hosp, Hamburg, Germany. [Thomas, P.] Univ Hosp Marseille, Marseille, France. [Madsen, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hertz, M.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. RI falcoz, pierre-emmanuel/N-1239-2016; Varela de Ugarte, Andres/B-4837-2017 OI Varela de Ugarte, Andres/0000-0001-8827-2454 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 164 BP S69 EP S69 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718100164 ER PT J AU Chatterjee, D Moore, C Gao, B Clerkin, KJ See, SB Shaked, D Rogers, KJ Nunez, S Veras, Y Addonizio, L Givertz, MM Naka, Y Mancini, D Vasilescu, R Marboe, C Restaino, S Madsen, JC Zorn, E AF Chatterjee, D. Moore, C. Gao, B. Clerkin, K. J. See, S. B. Shaked, D. Rogers, K. J. Nunez, S. Veras, Y. Addonizio, L. Givertz, M. M. Naka, Y. Mancini, D. Vasilescu, R. Marboe, C. Restaino, S. Madsen, J. C. Zorn, E. TI Prevalence of Polyreactive Innate-Like B Cells Among Graft-Infiltrating B Cells in Human Cardiac Allograft Vasculopathy SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Chatterjee, D.; Clerkin, K. J.; See, S. B.; Shaked, D.; Rogers, K. J.; Nunez, S.; Veras, Y.; Addonizio, L.; Naka, Y.; Mancini, D.; Restaino, S.; Zorn, E.] Columbia Univ, Dept Med, New York, NY USA. [Moore, C.; Madsen, J. C.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Gao, B.] Jilin Univ, Hosp 1, Changchun 130023, Peoples R China. [Givertz, M. M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Vasilescu, R.; Marboe, C.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 75 BP S36 EP S37 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718100076 ER PT J AU Danziger-Isakov, L Buller, R Williams, N Mason, S Fenchel, M Astor, T Conrad, C Faro, A Goldfarb, S Hayes, D Melicoff-Portillo, E Schecter, M Visner, G Ikle, D Storch, G Sweet, S AF Danziger-Isakov, L. Buller, R. Williams, N. Mason, S. Fenchel, M. Astor, T. Conrad, C. Faro, A. Goldfarb, S. Hayes, D. Melicoff-Portillo, E. Schecter, M. Visner, G. Ikle, D. Storch, G. Sweet, S. TI Respiratory Viral Infections Are Common in the First Year After Pediatric Lung Transplantation: A Multi-Center Prospective Study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Danziger-Isakov, L.; Fenchel, M.; Schecter, M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Buller, R.; Mason, S.; Faro, A.; Storch, G.; Sweet, S.] Washington Univ, St Louis, MO USA. [Williams, N.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Astor, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Conrad, C.] Lucille Packard Childrens Hosp, Palo Alto, CA USA. [Goldfarb, S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hayes, D.] Nationwide Childrens Hosp, Columbus, OH USA. [Melicoff-Portillo, E.] Texas Childrens Hosp, Houston, TX 77030 USA. [Visner, G.] Boston Childrens Hosp, Boston, MA USA. [Ikle, D.] Rho Inc, Chapel Hill, NC 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 71 BP S35 EP S35 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718100072 ER PT J AU Evrard, SM Milley, K Camuso, J Perkins, KE AF Evrard, S. M. Milley, K. Camuso, J. Perkins, K. E. TI Hospital Readmission and Survival Rates One Year Post-ECMO Discharge SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Evrard, S. M.; Milley, K.; Camuso, J.; Perkins, K. E.] Massachusetts Gen Hosp, Cardiac Surg, 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 930 BP S336 EP S336 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718101285 ER PT J AU Loor, G Warnecke, G Smith, M Kukreja, J Ardehali, A Moradiellos, J Varela, A Madsen, J Hertz, M Van Raemdonck, D AF Loor, G. Warnecke, G. Smith, M. Kukreja, J. Ardehali, A. Moradiellos, J. Varela, A. Madsen, J. Hertz, M. Van Raemdonck, D. TI The OCS Lung EXPAND International Trial Interim Results SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Loor, G.; Hertz, M.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Warnecke, G.] Hannover Med Sch, Hannover, Germany. [Smith, M.] St Josephs Med Ctr, Phoenix, AZ USA. [Kukreja, J.] Univ Calif San Francisco Md Ctr, San Francisco, CA USA. [Ardehali, A.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Moradiellos, J.; Varela, A.] Univ Puerta de Hierro Hosp, Madrid, Spain. [Madsen, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Van Raemdonck, D.] Leuven Univ Hosp, Leuven, Belgium. RI Varela de Ugarte, Andres/B-4837-2017 OI Varela de Ugarte, Andres/0000-0001-8827-2454 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 163 BP S68 EP S69 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718100163 ER PT J AU Milley, KD Evrard, SM Lewis, G D'Alessandro, DA MacGillivray, TE Wiafe, SC Camuso, JM Perkins, KE AF Milley, K. D. Evrard, S. M. Lewis, G. D'Alessandro, D. A. MacGillivray, T. E. Wiafe, S. C. Camuso, J. M. Perkins, K. E. TI Quality of Life among LVAD Recipients: A Comparison of Bridge-to Transplant vs. Destination Therapy Patients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Milley, K. D.; Evrard, S. M.; Camuso, J. M.] Massachusetts Gen Hosp, Cardiac Surg Res, Boston, MA 02114 USA. [Lewis, G.] Massachusetts Gen Hosp, Heart Failure Cardiol, Boston, MA 02114 USA. [D'Alessandro, D. A.; MacGillivray, T. E.; Perkins, K. E.] Massachusetts Gen Hosp, Cardiac Surg, Boston, MA 02114 USA. [Wiafe, S. 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 943 BP S341 EP S341 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718101298 ER PT J AU Moniodis, A Townsend, K Rabin, A Aloum, O Stempel, J Burkett, P Camp, P Divo, M El-Chemaly, S Mallidi, H Rosas, I Anne, F Koo, S Goldberg, H AF Moniodis, A. Townsend, K. Rabin, A. Aloum, O. Stempel, J. Burkett, P. Camp, P. Divo, M. El-Chemaly, S. Mallidi, H. Rosas, I. Anne, F. Koo, S. Goldberg, H. TI Natural History of Chronic Lung Allograft Dysfunction (CLAD) and Impact of Azithromycin (AZ) in Lung Transplant (LT) Recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Moniodis, A.] Brigham & Womens Hosp, Pulm & Crit Care, Brookline, MA USA. [Townsend, K.] Brigham & Womens Hosp, Dept Pharm, Lung Transplant Program, Brookline, MA USA. [Rabin, A.] Massachusetts Gen Hosp, Pulm & Crit Care, Boston, MA 02114 USA. [Aloum, O.; Stempel, J.; Koo, S.] Brigham & Womens Hosp, Transplant Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Burkett, P.; Divo, M.; El-Chemaly, S.; Rosas, I.; Anne, F.; Goldberg, H.] Brigham & Womens Hosp, Lung Transplant Program, 75 Francis St, Boston, MA 02115 USA. [Camp, P.] Brigham & Womens Hosp, Div Thorac Surg, Lung Transplant Program, 75 Francis St, Boston, MA 02115 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 603 BP S223 EP S223 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718100595 ER PT J AU Tapson, VF Channick, R Chin, K Di Scala, L Farber, H Gaine, S Galie, N Ghofrani, HA Lang, I McLaughlin, V Preiss, R Rubin, LJ Simonneau, G Sitbon, O Hoeper, MM AF Tapson, V. F. Channick, R. Chin, K. Di Scala, L. Farber, H. Gaine, S. Galie, N. Ghofrani, H. A. Lang, I. McLaughlin, V. Preiss, R. Rubin, L. J. Simonneau, G. Sitbon, O. Hoeper, M. M. TI Anticoagulant Therapy Is Not Associated with Long Term Outcome in Patients with Pulmonary Arterial Hypertension (PAH): Insights from the GRIPHON Study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Tapson, V. F.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Channick, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chin, K.] UT Southwestern Med Ctr, Dallas, TX USA. [Di Scala, L.; Preiss, R.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Farber, H.] Boston Univ, Sch Med, Pulm Hypertens Ctr, Boston, MA 02118 USA. [Gaine, S.] Mater Misericordiae Univ Hosp, Natl Pulm Hypertens Unit, Dublin, Ireland. [Galie, N.] Univ Bologna, Ist Malattie Apparato Cardiovasc, Bologna, Italy. [Ghofrani, H. A.] Univ Giessen & Marburg, Lung Ctr, Giessen, Germany. [Lang, I.] Med Univ Vienna, Dept Internal Med 2, Div Cardiol, Allgemeines Krankenhaus, Vienna, Austria. [McLaughlin, V.] Univ Michigan Hlth Syst, Div Cardiovasc Med, Ann Arbor, MI USA. [Rubin, L. J.] Univ Calif San Diego, Div Pulm & Crit Care Med, San Diego, CA 92103 USA. [Simonneau, G.; Sitbon, O.] Univ Paris 11, Hop Univ Bicetre, Le Kremlin Bicetre, France. [Hoeper, M. M.] Hannover Med Sch, Dept Resp Med, Hannover, Germany. [Hoeper, M. M.] German Ctr Lung Res, Hannover, Germany. NR 0 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 303 BP S120 EP S120 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718100302 ER PT J AU Thomas, SS Gallagher, R Steiner, J Song, TH Palacios, I Elmariah, S Wiafe, S Roy, N Cudemus, G Semigran, MJ Lewis, GD Garcia, JP Rosenfield, K AF Thomas, S. S. Gallagher, R. Steiner, J. Song, T. H. Palacios, I. Elmariah, S. Wiafe, S. Roy, N. Cudemus, G. Semigran, M. J. Lewis, G. D. Garcia, J. P. Rosenfield, K. TI Successful Capture of LVAD-EmboLi Using Carotid Filters Following Intra-Cavitary Thrombolysis for Pump Thrombosis SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Thomas, S. S.; Gallagher, R.; Steiner, J.; Palacios, I.; Elmariah, S.; Semigran, M. J.; Lewis, G. D.; Rosenfield, K.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA. [Song, T. H.; Wiafe, S.; Roy, N.; Garcia, J. P.] Massachusetts Gen Hosp, Cardiac Surg, Boston, MA 02114 USA. [Cudemus, G.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Management, 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 308 BP S122 EP S122 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718100307 ER PT J AU Townsend, K Moniodis, A Rabin, A Aloum, O Stempel, J Burkett, P Camp, P Divo, M El-Chemaly, S Mallidi, H Rosas, I Fuhlbrigge, A Goldberg, HJ Koo, S AF Townsend, K. Moniodis, A. Rabin, A. Aloum, O. Stempel, J. Burkett, P. Camp, P. Divo, M. El-Chemaly, S. Mallidi, H. Rosas, I. Fuhlbrigge, A. Goldberg, H. J. Koo, S. TI Comparison of Extracorporeal Photophoresis (ECP) or Alemtuzumab (AL) Treatment Efficacy for Chronic Lung Allograft Dysfunction (CLAD) SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Townsend, K.; Divo, M.] Brigham & Womens Hosp, Dept Pharm, Lung Transplant Program, 75 Francis St, Boston, MA 02115 USA. [Moniodis, A.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. [Rabin, A.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Aloum, O.; Stempel, J.; Koo, S.] Brigham & Womens Hosp, Div Infect Dis, Transplant Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Burkett, P.; El-Chemaly, S.; Rosas, I.; Fuhlbrigge, A.; Goldberg, H. J.] Brigham & Womens Hosp, Div Pulm Crit Care Med, Lung Transplant Program, 75 Francis St, Boston, MA 02115 USA. [Camp, P.; Mallidi, H.] Brigham & Womens Hosp, Div Thorac Surg, Lung Transplant Program, 75 Francis St, Boston, MA 02115 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 95 BP S44 EP S44 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718100096 ER PT J AU Warnecke, G Van Raemdonck, D Kukreja, J Smith, M Loor, G Rea, F Massard, G De Robertis, F Nagendran, J Moradiellos, J Dhital, K Knosalla, C Bermudez, C Tsui, S Madsen, J Wang, I McCurry, K Deuse, T Thomas, P Sommer, W Weigmann, B Khun, C Tudorache, I Avsar, M Schiavon, M Santelmo, N Olland, A Falcoz, P Varela, A Hertz, M Simon, A Resichenspurner, H Haverich, A Ardehali, A AF Warnecke, G. Van Raemdonck, D. Kukreja, J. Smith, M. Loor, G. Rea, F. Massard, G. De Robertis, F. Nagendran, J. Moradiellos, J. Dhital, K. Knosalla, C. Bermudez, C. Tsui, S. Madsen, J. Wang, I. McCurry, K. Deuse, T. Thomas, P. Sommer, W. Weigmann, B. Khun, C. Tudorache, I. Avsar, M. Schiavon, M. Santelmo, N. Olland, A. Falcoz, P. Varela, A. Hertz, M. Simon, A. Resichenspurner, H. Haverich, A. Ardehali, A. TI Mid and Long-Term Clinical Results of OCS Lung INSPIRE International Trial SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 36th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) CY APR 27-30, 2016 CL Washington, DC SP Int Soc Heart & Lung Transplantat C1 [Warnecke, G.; Sommer, W.; Weigmann, B.; Khun, C.; Tudorache, I.; Avsar, M.; Haverich, A.] Hannover Med Sch, Thorac Surg, Hannover, Germany. [Van Raemdonck, D.] Leuven Univ Hosp, Thorac Surg, Leuven, Belgium. [Kukreja, J.] Univ Calif San Francisco Med, Thorac Sug, San Francisco, CA USA. [Smith, M.] St Josephs Med Ctr, Thorac Sug, Phoenix, AZ USA. [Loor, G.] Univ Minnesota, Med Ctr, Cardiothorac Surg, Minneapolis, MN 55455 USA. [Rea, F.; Schiavon, M.] Univ Padua Hosp, Thorac Surg, Padua, Italy. [Massard, G.] Strasbourg Univ Hosp, Thorac Surg, Strasbourg, France. [De Robertis, F.; Simon, A.] Harefield Hosp, Thorac Surg, London, England. [Nagendran, J.] Univ Alberta, Med Ctr, Thorac Surg, Edmonton, ON, Canada. [Moradiellos, J.; Varela, A.] Univ Puerta de Hierro Hosp, Thorac Surg, Madrid, Spain. [Dhital, K.] St Vincents Hosp, Thorac Surg, Sydney, NSW 2010, Australia. [Knosalla, C.] German Heart Inst, Thorac Surg, Berlin, Germany. [Bermudez, C.] Univ Pittsburgh, Med Ctr, Thorac Surg, Pittsburgh, PA USA. [Tsui, S.] Papworth Hosp, Cardiothorac Surg, Papworth, Germany. [Madsen, J.] Massachusetts Gen Hosp, Cardiothorac Surg, Boston, MA 02114 USA. [Wang, I.] Indiana Univ, Med Ctr, Cardiothorac Surg, Indianapolis, IN USA. [McCurry, K.] Cleveland Clin Fdn, Thorac Surg, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Deuse, T.] Univ Hamburg Hosp, Thorac Surg, Hamburg, Germany. [Thomas, P.] Univ Hosp Marseille, Thorac Surg, Marseille, France. [Santelmo, N.; Olland, A.; Falcoz, P.] Strasbourg Univ Hosp, Thorac Surg, Strasbourg, France. [Hertz, M.] Univ Minnesota, Med Ctr, Transplant Pulm Med, Minneapolis, MN 55455 USA. [Resichenspurner, H.] Univ Hamburg Hosp, Cardiothorac Surg, Hamburg, Germany. [Ardehali, A.] Ronald Reagan UCLA Med Ctr, Cardiothorac Surg, Los Angeles, CA USA. RI falcoz, pierre-emmanuel/N-1239-2016; Varela de Ugarte, Andres/B-4837-2017 OI Varela de Ugarte, Andres/0000-0001-8827-2454 NR 0 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2016 VL 35 IS 4 SU S MA 19 BP S15 EP S16 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA DK2AX UT WOS:000374718100020 ER PT J AU Bowsher, K Civillico, EF Coburn, J Collinger, J Contreras-Vidal, JL Denison, T Donoghue, J French, J Getzoff, N Hochberg, LR Hoffmann, M Judy, J Kleitman, N Knaack, G Krauthamer, V Ludwig, K Moynahan, M Pancrazio, JJ Peckham, PH Pena, C Pinto, V Ryan, T Saha, D Scharen, H Shermer, S Skodacek, K Takmakov, P Tyler, D Vasudevan, S Wachrathit, K Weber, D Welle, CG Ye, M AF Bowsher, K. Civillico, E. F. Coburn, J. Collinger, J. Contreras-Vidal, J. L. Denison, T. Donoghue, J. French, J. Getzoff, N. Hochberg, L. R. Hoffmann, M. Judy, J. Kleitman, N. Knaack, G. Krauthamer, V. Ludwig, K. Moynahan, M. Pancrazio, J. J. Peckham, P. H. Pena, C. Pinto, V. Ryan, T. Saha, D. Scharen, H. Shermer, S. Skodacek, K. Takmakov, P. Tyler, D. Vasudevan, S. Wachrathit, K. Weber, D. Welle, C. G. Ye, M. TI Brain-computer interface devices for patients with paralysis and amputation: a meeting report SO JOURNAL OF NEURAL ENGINEERING LA English DT Article DE brain-computer interface; neuroprosthetic; regulation; translation; medical device ID PRIORITIES AB Objective. The Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) believes it is important to help stakeholders (e.g., manufacturers, health-care professionals, patients, patient advocates, academia, and other government agencies) navigate the regulatory landscape for medical devices. For innovative devices involving brain-computer interfaces, this is particularly important. Approach. Towards this goal, on 21 November, 2014, CDRH held an open public workshop on its White Oak, MD campus with the aim of fostering an open discussion on the scientific and clinical considerations associated with the development of brain-computer interface (BCI) devices, defined for the purposes of this workshop as neuroprostheses that interface with the central or peripheral nervous system to restore lost motor or sensory capabilities. Main results. This paper summarizes the presentations and discussions from that workshop. Significance. CDRH plans to use this information to develop regulatory considerations that will promote innovation while maintaining appropriate patient protections. FDA plans to build on advances in regulatory science and input provided in this workshop to develop guidance that provides recommendations for premarket submissions for BCI devices. These proceedings will be a resource for the BCI community during the development of medical devices for consumers. C1 [Bowsher, K.; Getzoff, N.; Hoffmann, M.; Pena, C.; Pinto, V.; Saha, D.; Scharen, H.; Shermer, S.; Skodacek, K.; Wachrathit, K.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD USA. [Civillico, E. F.; Coburn, J.; Knaack, G.; Krauthamer, V.; Takmakov, P.; Vasudevan, S.; Welle, C. G.; Ye, M.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD USA. [Collinger, J.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Contreras-Vidal, J. L.] Univ Houston, Elect & Comp Engn, Houston, TX USA. [Denison, T.] Medtronic Inc, Minneapolis, MN USA. [Donoghue, J.; Hochberg, L. R.] Brown Univ, Brown Inst Brain Sci, Sch Engn, Providence, RI 02912 USA. [French, J.] Neurotech Network, Tampa, FL 33623 USA. [Hochberg, L. R.] Ctr Neurorestorat & Neurotechnol, Rehabil R&D Serv, Dept Vet Affairs Med Ctr, Providence, RI USA. [Hochberg, L. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Judy, J.] Univ Florida, Coll Engn, Nanosci Inst Med & Engn Technol, Gainesville, FL 32611 USA. [Kleitman, N.] Craig H Neilsen Fdn, Encino, CA USA. [Ludwig, K.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Ludwig, K.] Mayo Clin, Dept Neurol Surg, Rochester, MN USA. [Moynahan, M.] Case Western Reserve Univ, Inst Funct Restorat, Cleveland, OH 44106 USA. [Pancrazio, J. J.] Univ Texas Dallas, Bioengn, Dallas, TX 75230 USA. [Peckham, P. H.; Tyler, D.] Case Western Reserve Univ, Sch Engn, Cleveland, OH 44106 USA. [Ryan, T.] Adv Arm Dynam, Redono Beach, CA 90277 USA. [Weber, D.] Def Adv Res Projects Agcy, Biol Technol Off, Arlington, VA USA. RP Bowsher, K (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD USA. RI Tyler, Dustin/C-7995-2015; OI Tyler, Dustin/0000-0002-2298-8510; Welle, Cristin/0000-0001-8735-0983; Pancrazio, Joseph/0000-0001-8276-3690; Takmakov, Pavel/0000-0001-6591-0257 NR 21 TC 3 Z9 3 U1 4 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD APR PY 2016 VL 13 IS 2 AR 023001 DI 10.1088/1741-2560/13/2/023001 PG 13 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA DL5NM UT WOS:000375683800004 PM 26924826 ER PT J AU Hessburg, PC Rizzo, J O'Malley, ER AF Hessburg, Philip C. Rizzo, Joseph O'Malley, Edward R. TI Preface: The Eye and The Chip world research congress on visual neuro-prosthetics SO JOURNAL OF NEURAL ENGINEERING LA English DT Editorial Material C1 [Hessburg, Philip C.] Henry Ford Hlth Syst, Detroit Inst Ophthalmol, Detroit, MI 48202 USA. [Rizzo, Joseph] Harvard Univ, MIT, Sch Med, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. [O'Malley, Edward R.] Henry Ford Hlth Syst, Henry Ford Med Ctr, Detroit Inst Ophthalmol, Detroit, MI USA. RP Hessburg, PC (reprint author), Henry Ford Hlth Syst, Detroit Inst Ophthalmol, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD APR PY 2016 VL 13 IS 2 AR 020401 DI 10.1088/1741-2560/13/2/020401 PG 1 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA DL5NM UT WOS:000375683800001 PM 26904980 ER PT J AU Im, M Fried, SI AF Im, Maesoon Fried, Shelley I. TI Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type SO JOURNAL OF NEURAL ENGINEERING LA English DT Article DE retinal prosthesis; electrical stimulation; temporal property; retinal ganglion cell; electrophysiology ID ELECTRICAL-STIMULATION; RETINITIS-PIGMENTOSA; MORPHOMETRIC-ANALYSIS; VISUAL-PERCEPTION; MAMMALIAN RETINA; EPIRETINAL PROSTHESIS; RECEPTIVE-FIELDS; RABBIT RETINA; INNER RETINA; MOUSE MODEL AB Objective. To provide artificially-elicited vision that is temporally dynamic, retinal prosthetic devices will need to repeatedly stimulate retinal neurons. However, given the diversity of physiological types of retinal ganglion cells (RGCs) as well as the heterogeneity of their responses to electric stimulation, temporal properties of RGC responses have not been adequately investigated. Here, we explored the cell type dependence of network-mediated RGC responses to repetitive electric stimulation at various stimulation rates. Approach. We examined responses of ON and OFF types of RGCs in the rabbit retinal explant to five consecutive stimuli with varying inter-stimulus intervals (10-1000ms). Each stimulus was a 4ms long monophasic sinusoidal cathodal current, which was applied epiretinally via a conical electrode. Spiking activity of targeted RGCs was recorded using a cell-attached patch electrode. Main results. ON and OFF cells had distinct responses to repetitive stimuli. Consistent with earlier studies, OFF cells always generated reduced responses to subsequent stimuli compared to responses to the first stimulus. In contrast, a new stimulus to ON cells suppressed all pending/ongoing responses from previous stimuli and initiated its own response that was remarkably similar to the response from a single stimulus in isolation. This previously unreported 'reset' behavior was observed exclusively and consistently in ON cells. These contrasts between ON and OFF cells created a range of stimulation rates (4-7Hz) that maximized the ratio of the responses arising in ON versus OFF cells. Significance. Previous clinical testing reported that subjects perceive bright phosphenes (ON responses) and also prefer stimulation rates of 5-7 Hz. Our results suggest that responses of ON cells are weak at high rates of stimulation (> similar to 7Hz) due to the reset while responses of OFF cells are strong at low rates (< similar to 4Hz) due to reduced desensitization, both reducing the ratio of ON to OFF responses. In combination with previous results indicating that responses in ON cells more closely match physiological patterns (Im and Fried 2015 J. Physiol. 593 3577-96), our results offer a potential reason for the user preference of intermediate rates (5-7Hz). C1 [Im, Maesoon; Fried, Shelley I.] VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. [Im, Maesoon; Fried, Shelley I.] Massachusetts Gen Hosp, Dept Neurosurg, 50 Blossom St, Boston, MA 02114 USA. [Im, Maesoon; Fried, Shelley I.] Harvard Univ, Sch Med, 50 Blossom St, Boston, MA 02114 USA. [Im, Maesoon] Henry Ford Hosp, Dept Ophthalmol, 1 Ford Pl, Detroit, MI 48202 USA. RP Im, M (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA.; Im, M (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 50 Blossom St, Boston, MA 02114 USA.; Im, M (reprint author), Harvard Univ, Sch Med, 50 Blossom St, Boston, MA 02114 USA.; Im, M (reprint author), Henry Ford Hosp, Dept Ophthalmol, 1 Ford Pl, Detroit, MI 48202 USA. EM Im.Maesoon@mgh.harvard.edu OI Im, Maesoon/0000-0003-1152-4398 FU VA Boston Healthcare System [1I01RX000350]; NIH [R01EY019967, R01EY023651] FX We thank Seung Woo Lee, Alex E Hadjinicolaou, Vineeth Raghuram, and Donald K Eddington for helpful discussion and review of the manuscript. This work was supported in part by the VA Boston Healthcare System (1I01RX000350) and by the NIH (R01EY019967, R01EY023651). NR 66 TC 1 Z9 1 U1 1 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD APR PY 2016 VL 13 IS 2 AR 025002 DI 10.1088/1741-2560/13/2/025002 PG 13 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA DL5NM UT WOS:000375683800006 PM 26905231 ER PT J AU Curley, EE Tung, ES Keuthen, NJ AF Curley, Erin E. Tung, Esther S. Keuthen, Nancy J. TI Trait anger, anger expression, and anger control in trichotillomania: Evidence for the emotion regulation model SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Trichotillomania; Hair Pulling; Emotion Regulation; Anger ID HAIRPULLING SCALE AB Researchers have proposed emotion regulation (ER) as one model of trichotillomania (TTM). This model suggests that hair pulling may function as a maladaptive coping mechanism given difficulty managing negative emotions such as anger. This study compared hair pullers versus the normative population on trait anger, anger expression, and anger control and explored whether there is a relationship between anger variables and hair pulling severity. 158 adult females with TTM or chronic hair pulling completed self-report measures of anger and hair pulling severity. Hair pullers reported significantly higher rates of inwardly directed anger and more difficulty controlling their inward anger. Frequency of inward directed anger was a significant predictor of hair pulling severity even after controlling for psychiatric illness, providing support for the ER model of TTM. These findings underscore the potential importance of understanding and addressing ER in TTM. (C) 2016 Elsevier Inc. All rights reserved. C1 [Curley, Erin E.; Keuthen, Nancy J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Tung, Esther S.] Boston Univ, Dept Psychol, 64 Cummington St, Boston, MA 02215 USA. [Keuthen, Nancy J.] Massachusetts Gen Hosp, Trichotillomania Clin, Simches Res Bldg,F1-2,185 Cambridge St, Boston, MA 02114 USA. RP Keuthen, NJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.; Keuthen, NJ (reprint author), Massachusetts Gen Hosp, Trichotillomania Clin, Simches Res Bldg,F1-2,185 Cambridge St, Boston, MA 02114 USA. EM nkeuthen@partners.org FU Trichotillomania Learning Center, Inc. (TLC) and its BFRB Precision Medicine Initiative; Greater Kansas City Foundation FX Funding for this study was provided by the Trichotillomania Learning Center, Inc. (TLC) and its BFRB Precision Medicine Initiative, as well as the Greater Kansas City Foundation. Neither TLC nor the Greater Kansas City Foundation had any role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. NR 15 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-3649 J9 J OBSESS-COMPULS REL JI J. Obsessive-Compuls. Relat. Disord. PD APR PY 2016 VL 9 BP 77 EP 81 DI 10.1016/j.jocrd.2016.04.005 PG 5 WC Psychiatry SC Psychiatry GA DL7ME UT WOS:000375824000012 ER PT J AU Jain, N Steensma, D Stewart, DJ Kantarjian, H AF Jain, Nitin Steensma, David Stewart, David J. Kantarjian, Hagop TI Insurance Denial of Coverage for Patients Enrolled in Cancer Clinical Trials Is Still a Problem in the Affordable Care Act Era SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Ottawa, Ottawa, ON, Canada. RP Kantarjian, H (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe Blvd,Unit 428, Houston, TX 77030 USA. EM hkantarjian@mdanderson.org FU NCI NIH HHS [P30 CA016672] NR 12 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD APR PY 2016 VL 12 IS 4 BP 283 EP 286 DI 10.1200/JOP.2015.010454 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LW UT WOS:000374325700015 PM 26907450 ER PT J AU Richardson, PG AF Richardson, Paul G. TI The Future of Myeloma Therapy: One Size Does Not Fit All SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material ID MULTIPLE-MYELOMA C1 [Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 450 Brookline Ave, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 10 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 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD APR PY 2016 VL 12 IS 4 BP 295 EP + DI 10.1200/JOP.2016.011502 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LW UT WOS:000374325700018 PM 27072382 ER PT J AU Wong, JS AF Wong, Julia S. TI Ductal Carcinoma In Situ: To Irradiate or Not to Irradiate? SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material ID BREAST-CONSERVING THERAPY; RADIOTHERAPY; TRIAL; WOMEN; OUTCOMES; DCIS; LUMPECTOMY; RECURRENCE; TAMOXIFEN; EXCISION C1 [Wong, Julia S.] Harvard Univ, Sch Med, Boston, MA USA. RP Wong, JS (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM jwong@lroc.harvard.edu NR 18 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 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD APR PY 2016 VL 12 IS 4 BP 314 EP + DI 10.1200/JOP.2016.011387 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LW UT WOS:000374325700024 PM 27072388 ER PT J AU Burstein, HJ Lacchetti, C Griggs, JJ AF Burstein, Harold J. Lacchetti, Christina Griggs, Jennifer J. TI Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression Summary SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID PREMENOPAUSAL WOMEN; ABLATION; TRIAL C1 Dana Farber Canc Inst, Boston, MA 02115 USA. ASCO, Alexandria, VA USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Lacchetti, C (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM guidelines@asco.org NR 9 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD APR PY 2016 VL 12 IS 4 BP 390 EP + DI 10.1200/JOP.2016.011239 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LW UT WOS:000374325700027 PM 26931400 ER PT J AU Lennes, IT Bohlen, N Park, ER Mort, E Burke, D Ryan, DP AF Lennes, Inga T. Bohlen, Nie Park, Elyse R. Mort, Elizabeth Burke, Debra Ryan, David P. TI Chemotherapy Errors: A Call for a Standardized Approach to Measurement and Reporting SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID PATIENT SAFETY; STRATEGIES AB The Massachusetts General Hospital (MGH) Cancer Center is a multidisciplinary cancer center that delivers chemotherapy to 150 to 200 patients daily and adheres to the Oncology Nursing Society and ASCO guidelines for safe chemotherapy administration. An error that occurred at MGH in the summer of 2012 prompted a review of all safety events, the process of classification, and the monitoring of safety events. This article reviews safety monitoring in the oncology setting, details the oncology safety-event reporting program at MGH, summarizes all chemotherapy-related safety events that have occurred over the past 5 years, and concludes with summary recommendations and potential steps to standardize safety reporting and analysis in chemotherapy administration. C1 [Lennes, Inga T.; Bohlen, Nie; Park, Elyse R.; Mort, Elizabeth; Burke, Debra; Ryan, David P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lennes, IT (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM ilennes@partners.org NR 7 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 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD APR PY 2016 VL 12 IS 4 BP E495 EP E501 DI 10.1200/JOP.2015.008995 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LW UT WOS:000374325700013 PM 26957639 ER PT J AU Warren, LEG Kim, MB Martin, NE Shih, HA AF Warren, Laura E. G. Kim, Miranda B. Martin, Neil E. Shih, Helen A. TI Analysis of After-Hours Patient Telephone Calls in Two Academic Radiation Oncology Departments: An Opportunity for Improvement in Patient Safety and Quality of Care SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID PEDIATRIC PRACTICE; ELDERLY-PATIENTS; EXPERIENCE; MEDICINE AB Purpose Patient care within radiation oncology extends beyond the clinic or treatment hours. The on-call radiation oncologist is often not a patient's primary radiation oncologist, introducing the possibility of communication breakdowns and medical errors. This study analyzed after-hours telephone calls to identify opportunities for improved patient safety and quality of care. Methods and Materials Patient calls received outside of business hours between July 1, 2013, and June 30, 2014, at two academic radiation oncology departments were retrospectively reviewed. All calls were analyzed using content analysis, and descriptive analyses were performed. Results During this time, 5,557 courses of radiotherapy (RT) were delivered. A total of 454 calls were received from 369 unique patients (81%), averaging 4.4 calls per week per department. Phone encounters were documented for 223 calls (49%). The calls were categorized by disease site (No., %): central nervous system (91, 20%), head and neck (78, 17%), genitourinary (53, 12%), GI (52, 12%), thoracic (51, 11%), gynecologic (30, 7%), breast (24, 5%), and other (75, 17%). Patients most often called regarding acute medical, non-RT-related issues (144 calls, 32%); acute RT-related adverse effects (127, 28%); and medication management, including refills (63, 14%). Conclusion This analysis provided novel information regarding the volume of and reasons for after-hours patient-initiated telephone calls. It identified opportunities for actionable improvements in safety and quality of care, particularly with regard to documentation by on-call providers, communication with the primary radiation oncology and extended health care teams, patient education about common RT adverse effects, and medication management. C1 Brigham & Womens Hosp, Harvard Radiat Oncol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Warren, LEG (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, 75 Francis St,ASB-I,L2, Boston, MA 02115 USA. EM lewarren@partners.org NR 18 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD APR PY 2016 VL 12 IS 4 BP E487 EP E494 DI 10.1200/JOP.2015.007583 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LW UT WOS:000374325700012 PM 26907449 ER PT J AU LeBaron, VT Smith, PT Quinones, R Nibecker, C Sanders, JJ Timms, R Shields, AE Balboni, TA Balboni, MJ AF LeBaron, Virginia T. Smith, Patrick T. Quinones, Rebecca Nibecker, Callie Sanders, Justin J. Timms, Richard Shields, Alexandra E. Balboni, Tracy A. Balboni, Michael J. TI How Community Clergy Provide Spiritual Care: Toward a Conceptual Framework for Clergy End-of-Life Education SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Religion; spirituality; spiritual care; end of life; clergy; palliative care; education ID ADVANCED CANCER; SUPPORT; ASSOCIATIONS; AMERICANS; QUALITY; DEATH AB Context. Community-based clergy are highly engaged in helping terminally ill patients address spiritual concerns at the end of life (EOL). Despite playing a central role in EOL care, clergy report feeling ill-equipped to spiritually support patients in this context. Significant gaps exist in understanding how clergy beliefs and practices influence EOL care. Objectives. The objective of this study was to propose a conceptual framework to guide EOL educational programming for community-based clergy. Methods. This was a qualitative, descriptive study. Clergy from varying spiritual backgrounds, geographical locations in the U.S., and race/ethnicities were recruited and asked about optimal spiritual care provided to patients at the EOL. Interviews were audio taped, transcribed, and analyzed following principles of grounded theory. A final set of themes and subthemes were identified through an iterative process of constant comparison. Participants also completed a survey regarding experiences ministering to the terminally ill. Results. A total of 35 clergy participated in 14 individual interviews and two focus groups. Primary themes included Patient Struggles at EOL and Clergy Professional Identity in Ministering to the Terminally Ill. Patient Struggles at EOL focused on existential questions, practical concerns, and difficult emotions. Clergy Professional Identity in Ministering to the Terminally Ill was characterized by descriptions of Who Clergy Are ("Being"), What Clergy Do ("Doing"), and What Clergy Believe ("Believing"). "Being" was reflected primarily by manifestations of presence; "Doing" by subthemes of religious activities, spiritual support, meeting practical needs, and mistakes to avoid; "Believing" by subthemes of having a relationship with God, nurturing virtues, and eternal life. Survey results were congruent with interview and focus group findings. Conclusion. A conceptual framework informed by clergy perspectives of optimal spiritual care can guide EOL educational programming for clergy. (c) 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [LeBaron, Virginia T.] Univ Virginia, Sch Nursing, 202 Jeannette Lancaster Way, Charlottesville, VA 22908 USA. [Smith, Patrick T.] Harvard Univ, Sch Med, Ctr Bioeth, Boston, MA USA. [Smith, Patrick T.] Gordon Conwell Theol Seminary, Boston, MA USA. [Quinones, Rebecca; Nibecker, Callie; Sanders, Justin J.; Balboni, Tracy A.; Balboni, Michael J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Timms, Richard] Scripps Clin, La Jolla, CA 92037 USA. [Shields, Alexandra E.] Massachusetts Gen Hosp, Harvard MGH Ctr Gen Vulnerable Populat & Hlth Dis, Boston, MA 02114 USA. [Balboni, Tracy A.; Balboni, Michael J.] Harvard Univ, Initiat Hlth Relig & Spiritual, Cambridge, MA 02138 USA. RP LeBaron, VT (reprint author), Univ Virginia, Sch Nursing, 202 Jeannette Lancaster Way, Charlottesville, VA 22908 USA. EM vlebaron@virginia.edu FU NCI NIH HHS [CA156732, U54 CA156732] NR 22 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD APR PY 2016 VL 51 IS 4 BP 673 EP 681 DI 10.1016/j.jpainsymman.2015.11.016 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DK1FK UT WOS:000374657700006 PM 26706624 ER PT J AU Merchant, AT Nahhas, GJ Wadwa, RP Zhang, JJ Tang, YF Johnson, LR Maahs, DM Bishop, F Teles, R Morrato, EH AF Merchant, Anwar T. Nahhas, Georges J. Wadwa, R. Paul Zhang, Jiajia Tang, Yifan Johnson, Lonnie R. Maahs, David M. Bishop, Franziska Teles, Ricardo Morrato, Elaine H. TI Periodontal Microorganisms and Cardiovascular Risk Markers in Youth With Type 1 Diabetes and Without Diabetes SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Adolescent; blood pressure; diabetes mellitus; type 1; hemoglobin A; glycosylated; microbiology; periodontal diseases ID PORPHYROMONAS-GINGIVALIS; DISEASE RISK; INFLAMMATION; CHILDREN; CHOLESTEROL; INFECTIONS; MELLITUS; ATHEROSCLEROSIS; COMPLICATIONS; ASSOCIATION AB Background: A subset of periodontal microorganisms has been associated with cardiovascular disease (CVD), which is the leading complication of type 1 diabetes (t1DM). The authors therefore evaluated the association between periodontal microorganism groups and early markers of CVD in youth with t1DM. Methods: A cross-sectional analysis was conducted among youth aged 12 to 19 years at enrollment; 105 had t1DM for >= 5 years and were seeking care at the Barbara Davis Center, University of Colorado, from 2009 to 2011, and 71 did not have diabetes. Subgingival plaque samples were assessed for counts of 41 periodontal microorganisms using DNA-DNA hybridization. Microorganisms were classified using cluster analysis into four groups named red-orange, orange-green, blue/other, and yellow/other, modified from Socransky's color scheme for periodontal microorganisms. Subsamples (54 with t1DM and 48 without diabetes) also received a periodontal examination at the University of Colorado School of Dental Medicine. Results: Participants were approximate to 15 years old on average, and 74% were white. Mean periodontal probing depth was 2 mm (SE 0.02), and 17% had bleeding on probing. In multivariable analyses, glycated hemoglobin (HbA1c) was inversely associated with the yellow/other cluster (microorganisms that are not associated with periodontal disease) among youth with t1DM. Blood pressure, triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol were not associated with microorganism clusters in this group. HbA1c was not associated with periodontal microorganism clusters among youth without diabetes. Conclusion: Among youth with t1DM who had good oral health, periodontal microorganisms were not associated with CVD risk factors. C1 [Merchant, Anwar T.; Nahhas, Georges J.; Zhang, Jiajia; Tang, Yifan] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Wadwa, R. Paul; Johnson, Lonnie R.; Maahs, David M.; Bishop, Franziska; Morrato, Elaine H.] Univ Colorado, Anschutz Med Campus, Aurora, CO USA. [Teles, Ricardo] Forsyth Inst, Cambridge, MA USA. RP Merchant, AT (reprint author), Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, 915 Greene St,Room 455, Columbia, SC 29208 USA. EM merchant@mailbox.sc.edu FU American Diabetes Association, Alexandria, Virginia [7-11-CT-27]; University of Colorado Pediatric Clinical Translational Research Center [5 M01 RR00069]; General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health (NIH); NIH, Bethesda, Maryland [K23 DK075360]; Juvenile Diabetes Research Foundation New York, New York [11-2007-694]; Delta Dental Frontier Center (EHM); Colorado Children's Outcomes Research Program FX This study was supported by the American Diabetes Association, Award No. 7-11-CT-27, Alexandria, Virginia; University of Colorado Pediatric Clinical Translational Research Center Grant No. 5 M01 RR00069; General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health (NIH); NIH K23 DK075360 (DMM), Bethesda, Maryland; the Juvenile Diabetes Research Foundation 11-2007-694 (RPW) New York, New York; the Delta Dental Frontier Center (EHM); the Colorado Children's Outcomes Research Program; and an unrestricted gift from Procter & Gamble, Cincinnati, Ohio. The authors report no conflicts of interest related to this study. NR 35 TC 0 Z9 0 U1 3 U2 3 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD APR PY 2016 VL 87 IS 4 BP 376 EP 384 DI 10.1902/jop.2015.150531 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DL7TK UT WOS:000375842800008 PM 26616842 ER PT J AU Lee, CT Tao, CY Stoupel, J AF Lee, Chun-Teh Tao, Chih-Yun Stoupel, Janet TI The Effect of Subepithelial Connective Tissue Graft Placement on Esthetic Outcomes After Immediate Implant Placement: Systematic Review (vol 87, pg 156, 2016) SO JOURNAL OF PERIODONTOLOGY LA English DT Correction C1 [Lee, Chun-Teh] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. [Lee, Chun-Teh] Univ Texas Hlth Sci Ctr Houston, Dept Periodont & Dent Hyg, Houston, TX 77030 USA. [Tao, Chih-Yun] Natl Taiwan Univ, Sch Dent, Dept Dent, Taipei 10764, Taiwan. [Stoupel, Janet] Columbia Univ, Coll Dent Med, Sect Oral & Diagnost Sci, Div Periodont, New York, NY USA. RP Lee, CT (reprint author), Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA.; Lee, CT (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Periodont & Dent Hyg, Houston, TX 77030 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD APR PY 2016 VL 87 IS 4 BP 492 EP 492 DI 10.1902/jop.2016.164003 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DL7TK UT WOS:000375842800019 ER PT J AU Ruderfer, DM Charney, AW Readhead, B Kidd, BA Kahler, AK Kenny, PJ Keiser, MJ Moran, JL Hultman, CM Scott, SA Sullivan, PF Purcell, SM Dudley, JT Sklar, P AF Ruderfer, Douglas M. Charney, Alexander W. Readhead, Ben Kidd, Brian A. Kahler, Anna K. Kenny, Paul J. Keiser, Michael J. Moran, Jennifer L. Hultman, Christina M. Scott, Stuart A. Sullivan, Patrick F. Purcell, Shaun M. Dudley, Joel T. Sklar, Pamela TI Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach SO LANCET PSYCHIATRY LA English DT Article ID TREATMENT-RESISTANT SCHIZOPHRENIA; WIDE ASSOCIATION; DRUG-METABOLISM; LOCI; METAANALYSIS; EFFICACY; BURDEN; RARE AB Background Therapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk. We aimed to examine the overlap between schizophrenia risk loci and gene targets of a comprehensive set of medications to potentially inform and improve treatment of schizophrenia. Methods We defined schizophrenia risk loci as genomic regions reaching genome-wide significance in the latest Psychiatric Genomics Consortium schizophrenia genome-wide association study (GWAS) of 36 989 cases and 113 075 controls and loss of function variants observed only once among 5079 individuals in an exome-sequencing study of 2536 schizophrenia cases and 2543 controls (Swedish Schizophrenia Study). Using two large and orthogonally created databases, we collated drug targets into 167 gene sets targeted by pharmacologically similar drugs and examined enrichment of schizophrenia risk loci in these sets. We further linked the exome-sequenced data with a national drug registry (the Swedish Prescribed Drug Register) to assess the contribution of rare variants to treatment response, using clozapine prescription as a proxy for treatment resistance. Findings We combined results from testing rare and common variation and, after correction for multiple testing, two gene sets were associated with schizophrenia risk: agents against amoebiasis and other protozoal diseases (106 genes, p=0.00046, p(corrected) = 0.024) and antipsychotics (347 genes, p=0.00078, p(corrected)=0.046). Further analysis pointed to antipsychotics as having independent enrichment after removing genes that overlapped these two target sets. We noted significant enrichment both in known targets of antipsychotics (70 genes, p=0.0078) and novel predicted targets (277 genes, p=0.019). Patients with treatment-resistant schizophrenia had an excess of rare disruptive variants in gene targets of antipsychotics (347 genes, p=0.0067) and in genes with evidence for a role in antipsychotic efficacy (91 genes, p=0.0029). Interpretation Our results support genetic overlap between schizophrenia pathogenesis and antipsychotic mechanism of action. This finding is consistent with treatment efficacy being polygenic and suggests that single-target therapeutics might be insufficient. We provide evidence of a role for rare functional variants in antipsychotic treatment response, pointing to a subset of patients where their genetic information could inform treatment. Finally, we present a novel framework for identifying treatments from genetic data and improving our understanding of therapeutic mechanism. C1 [Ruderfer, Douglas M.; Charney, Alexander W.; Purcell, Shaun M.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA. [Ruderfer, Douglas M.; Charney, Alexander W.; Readhead, Ben; Kidd, Brian A.; Purcell, Shaun M.; Dudley, Joel T.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Readhead, Ben; Kidd, Brian A.; Scott, Stuart A.; Purcell, Shaun M.; Dudley, Joel T.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Kenny, Paul J.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Sklar, Pamela] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Ruderfer, Douglas M.; Purcell, Shaun M.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Ruderfer, Douglas M.; Moran, Jennifer L.; Purcell, Shaun M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Kahler, Anna K.; Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Keiser, Michael J.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA USA. [Keiser, Michael J.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Keiser, Michael J.] Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Purcell, Shaun M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Ruderfer, DM (reprint author), Icahn Sch Med Mt Sinai, New York, NY 10029 USA. EM douglas.ruderfer@mssm.edu RI Ruderfer, Douglas/M-5795-2016; OI Ruderfer, Douglas/0000-0002-2365-386X; Keiser, Michael/0000-0002-1240-2192; Moran, Jennifer/0000-0002-5664-4716 FU US National Institutes of Health FX US National Institutes of Health. NR 33 TC 5 Z9 5 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2215-0374 J9 LANCET PSYCHIAT JI Lancet Psychiatry PD APR PY 2016 VL 3 IS 4 BP 350 EP 357 DI 10.1016/S2215-0366(15)00553-2 PG 8 WC Psychiatry SC Psychiatry GA DJ5NE UT WOS:000374254600023 PM 26915512 ER PT J AU Padilla-Martinez, JP Wang, RS Franco, W AF Padilla-Martinez, Juan Pablo Wang, Ruisheng Franco, Walfre TI Evaluation of cell and matrix mechanics using fluorescence excitation spectroscopy: Feasibility study in collagen gels containing fibroblasts SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE extracellular matrix; collagen gel; autofluorescence; elastic modulus; indentation; fibroblast; collagen cross-links; tryptophan ID SOFT BIOLOGICAL TISSUES; YOUNGS MODULUS; IN-VIVO; SKIN; PHOTOTHERAPY; MICROSCOPY; BAND AB Background and ObjectiveCollagen gels containing cells are commonly used in tissue engineering, wound healing, and cancer research to investigate the interplay between cells and the extracellular matrix (ECM), as changes in the density and stiffness of the microenvironment are known to play a role in many diseases or pathological conditions. In these gels, the stiffness is regularly determined using destructive methods, such as indentation and tensile tests. Certain molecules native to cells and the ECM display fluorescence upon irradiation with ultraviolet light. The objective of the present study was to investigate the feasibility of using the endogenous, or innate, fluorescence of collagen gels containing fibroblasts as an optical marker to evaluate changes in the mechanical properties of the ECM. Materials and MethodsHuman foreskin fibroblasts cells at concentrations of 50,000 and 100,000 cells/ml were cultured in three-dimensional gels of type I collagen for 16 days. Fibroblast cells remodeled the ECM, contracting and increasing the stiffness of the gel. During this remodeling process, changes in mechanical properties and fluorescence were measured with an indentation test and a spectrofluorometer, respectively. Force and displacement measurements from the indentation test were used to calculate the elastic modulus of the gel. Maps of fluorescence intensity, at excitation/emission of 240-520/290-530nm, were used to identify the wavelengths of interest. ResultsFluorescence excitation/emission maps exhibited two distinct excitation/emission bands whose intensities increased as the fibroblasts remodeled and increased the stiffness of the ECM: The 290/340nm band ascribed to tryptophan and the 330/390nm band ascribed to cross-links of collagen (pepsin-digestible cross-links). A Spearman correlation analysis, between the elastic modulus of the gel containing fibroblasts and the fluorescence of cross-links of collagen, resulted in R=0.95 (P<0.05) and R=0.77 (P=0.12) for 50,000 and 100,000cells/ml, respectively. ConclusionsThe endogenous fluorescence intensity ascribed to pepsin-digestible cross-links of collagen may serve as an optical marker to evaluate changes in the mechanical properties of the ECM; this is relevant to collagenous tissues for which pathological states are related to mechanical alterations, such as keratoconus in cornea and osteoarthritis in articular cartilage. Lasers Surg. Med. 48:377-384, 2016. (c) 2016 Wiley Periodicals, Inc. C1 [Padilla-Martinez, Juan Pablo; Franco, Walfre] Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St Thier 209, Boston, MA 02114 USA. [Padilla-Martinez, Juan Pablo; Franco, Walfre] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Wang, Ruisheng] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA. RP Franco, W (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St Thier 209, Boston, MA 02114 USA. EM wfranco@mgh.harvard.edu NR 27 TC 1 Z9 1 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2016 VL 48 IS 4 BP 377 EP 384 DI 10.1002/lsm.22501 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA DK1WN UT WOS:000374705800008 PM 26990874 ER PT J AU Bayona, AMD Macrobert, A Hamblin, M AF Bayona, Alejandra Martinez De Pinillos Macrobert, Alexander Hamblin, Michael TI STIMULATION OF DENDRITIC CELLS AFTER PHOTOCHEMICAL INTERNALIZATION (PCI), IMPLICATIONS IN CANCER TREATMENT SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY MAR 30-APR 03, 2016 CL Boston, MA SP Amer Soc Laser Med & Surg C1 UCL, London WC1E 6BT, England. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, 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 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2016 VL 48 IS 4 MA LB2 BP 420 EP 420 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA DK1WN UT WOS:000374705800015 ER PT J AU Shek, SYN Negishi, K Tanaka, S Yeung, CK Chan, HHL AF Shek, Samantha Y. N. Negishi, Kei Tanaka, Shiho Yeung, Chi K. Chan, Henry H. L. TI A PROSPECTIVE MULTI-CENTER STUDY OF A DUAL-WAVELENGTH LASER PICOSECOND FOR THE TREATMENT OF MELASMA AND LENTIGINES IN ASIAN SKIN SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY MAR 30-APR 03, 2016 CL Boston, MA SP Amer Soc Laser Med & Surg C1 Tokyo Womens Med Univ, Aoyama Inst Womens Med, Tokyo, Japan. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2016 VL 48 IS 4 MA LB5 BP 421 EP 421 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA DK1WN UT WOS:000374705800018 ER PT J AU Avram, M Eshleman, E Hu, R Xu, V LeBlanc, M Rokoff, L AF Avram, Mathew Eshleman, Emily Hu, Rui Xu, Veronica LeBlanc, Mallory Rokoff, Lisa TI LASER HAIR REMOVAL: WHATIS IN THE PLUME? SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY MAR 30-APR 03, 2016 CL Boston, MA SP Amer Soc Laser Med & Surg C1 [Avram, Mathew; Eshleman, Emily; Hu, Rui; Xu, Veronica; LeBlanc, Mallory; Rokoff, Lisa] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2016 VL 48 IS 4 MA LB22 BP 427 EP 427 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA DK1WN UT WOS:000374705800036 ER PT J AU Martinez, AO Ortega-Martinez, A Gutierrez-Herrera, E Franco, W AF Ortega Martinez, Antonio Ortega-Martinez, Antonio Gutierrez-Herrera, Enoch Franco, Walfre TI DESIGN AND TESTING OF A PORTABLE, INTRAMUSCULAR, PHASE-MODULATED, OPTICAL OXYGEN SENSOR SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY MAR 30-APR 03, 2016 CL Boston, MA SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Nacl Autonoma Mexico, Mexico City 04510, DF, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2016 VL 48 IS 4 MA E16 BP 439 EP 439 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA DK1WN UT WOS:000374705800070 ER PT J AU Sajjadi, A Carp, S Manstein, D AF Sajjadi, Amir Carp, Stefan Manstein, Dieter TI NEAR-INFRARED SPECTROSCOPY OF TEMPERATURE INDUCED PHASE CHANGE KINETICS IN SUBCUTANEOUS FATTY TISSUES SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY MAR 30-APR 03, 2016 CL Boston, MA SP Amer Soc Laser Med & Surg C1 [Sajjadi, Amir; Carp, Stefan; Manstein, Dieter] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2016 VL 48 IS 4 MA E39 BP 446 EP 447 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA DK1WN UT WOS:000374705800093 ER PT J AU Silva, ZS Silva, ZS Huang, YY Freitas, L Mesquita-Ferrari, R Fernandes, K Franca, C Prates, R Hamblin, M Bussadori, S AF Silva, Zenildo Santos, Jr. Silva, Zenildo Santos, Jr. Huang, Yingying Freitas, Lucas Mesquita-Ferrari, Raquel Fernandes, Kristianne Franca, Cristiane Prates, Renato Hamblin, Michael Bussadori, Sandra TI PAPAIN GEL CONTAINING METHYLENE BLUE FOR SIMULTANEOUS CARIES REMOVAL AND ANTIMICROBIAL PHOTOINACTIVATION AGAINST STREPTOCOCCUS MUTANS BIOFILMS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY MAR 30-APR 03, 2016 CL Boston, MA SP Amer Soc Laser Med & Surg C1 Nove de Julho Univ, Massachusetts Gen Hosp, Wellman Ctr, Harvard Med Sch, Sao Paulo, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr, Boston, MA USA. Univ Sao Paulo, Massachusetts Gen Hosp, Wellman Ctr, Harvard Med Sch Sao Carlos, BR-05508 Sao Paulo, Brazil. Nove de Julho Univ, Sao Paulo, Brazil. RI Ferrari, Raquel/I-4419-2016; Fernandes, Kristianne/I-4417-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2016 VL 48 IS 4 MA E44 BP 448 EP 448 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA DK1WN UT WOS:000374705800098 ER PT J AU Hoang, B Shi, YJ Frost, PJ Mysore, V Bardeleben, C Lichtenstein, A AF Hoang, Bao Shi, Yijiang Frost, Patrick J. Mysore, Veena Bardeleben, Carolyne Lichtenstein, Alan TI SGK Kinase Activity in Multiple Myeloma Cells Protects against ER Stress Apoptosis via a SEK-Dependent Mechanism SO MOLECULAR CANCER RESEARCH LA English DT Article ID PRECLINICAL MODELS; PATHWAY; GENE; INHIBITOR; SERUM; AKT; SURVIVAL; RECEPTOR; GROWTH; PHOSPHORYLATION AB To assess the role of the serum and glucocorticoid-regulated kinase (SGK) kinase in multiple myeloma, we ectopically expressed wild type or a phosphomimetic version of SGK into multiple myeloma cell lines. These cells were specifically resistant to the ER stress inducers tunicamycin, thapsigargin, and bortezomib. In contrast, there was no alteration of sensitivity to dexamethasone, serum starvation, or mTORC inhibitors. Mining of genomic data from a public database indicated that low baseline SGK expression in multiple myeloma patients correlated with enhanced ability to undergo a complete response to subsequent bortezomib treatment and a longer time to progression and overall survival following treatment. SGK overexpressing multiple myeloma cells were also relatively resistant to bortezomib in a murine xenograft model. Parental/control multiple myeloma cells demonstrated a rapid upregulation of SGK expression and activity (phosphorylation of NDRG-1) during exposure to bortezomib and an SGK inhibitor significantly enhanced bortezomib-induced apoptosis in cell lines and primary multiple myeloma cells. In addition, a multiple myeloma cell line selected for bortezomib resistance demonstrated enhanced SGK expression and SGK activity. Mechanistically, SGK overexpression constrained an ER stress-induced JNK proapoptotic pathway and experiments with a SEK mutant supported the notion that SGK's protection against bortezomib was mediated via its phosphorylation of SEK (MAP2K4) which abated SEK/JNK signaling. These data support a role for SGK inhibitors in the clinical setting for myeloma patients receiving treatment with ER stress inducers like bortezomib. Implications: Enhanced SGK expression and activity in multiple myeloma cells contributes to resistance to ER stress, including bortezomib challenge. Mol Cancer Res; 14(4); 397-407. (C) 2016 AACR. C1 [Hoang, Bao; Shi, Yijiang; Frost, Patrick J.; Mysore, Veena; Bardeleben, Carolyne; Lichtenstein, Alan] UCLA Med Ctr, Johnsson Comprehens Canc Ctr, Div Hematol Oncol, Greater Los Angeles VA Healthcare Ctr,Dept Med, Los Angeles, CA 90073 USA. RP Lichtenstein, A (reprint author), UCLA Med Ctr, West Los Angeles VA Med Center, 11301 Wilshire Blvd,Bldg 304,Room E1-115, Los Angeles, CA 90073 USA. EM alan.lichtenstein@med.va.gov FU NIH [RO1CA168700, 2RO1CA111448, R21CA168491]; Veteran's Administration; Multiple Myeloma Research Foundation; CURE grant [P30 DK041301] FX This work was supported by NIH grants RO1CA168700, 2RO1CA111448, and R21CA168491 as well as research funds of the Veteran's Administration and Multiple Myeloma Research Foundation. The UCLA Vector Core Lab was supported by CURE grant P30 DK041301. NR 29 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 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2016 VL 14 IS 4 BP 397 EP 407 DI 10.1158/1541-7786.MCR-15-0422 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DL7WX UT WOS:000375852200009 PM 26869290 ER PT J AU Yard, BD Adams, DJ Chie, EK Tamayo, P Battaglia, JS Gopal, P Rogacki, K Pearson, BE Phillips, J Raymond, DP Pennell, NA Almeida, F Cheah, JH Clemons, PA Shamji, A Peacock, CD Schreiber, SL Hammerman, PS Abazeed, ME AF Yard, Brian D. Adams, Drew J. Chie, Eui Kyu Tamayo, Pablo Battaglia, Jessica S. Gopal, Priyanka Rogacki, Kevin Pearson, Bradley E. Phillips, James Raymond, Daniel P. Pennell, Nathan A. Almeida, Francisco Cheah, Jaime H. Clemons, Paul A. Shamji, Alykhan Peacock, Craig D. Schreiber, Stuart L. Hammerman, Peter S. Abazeed, Mohamed E. TI A genetic basis for the variation in the vulnerability of cancer to DNA damage SO NATURE COMMUNICATIONS LA English DT Article ID COPY-NUMBER ALTERATION; CELL LUNG-CANCER; COMPREHENSIVE GENOMIC CHARACTERIZATION; BREAST-CANCER; ANDROGEN RECEPTOR; PROSTATE-CANCER; PHOSPHATIDYLINOSITOL 3-KINASE; RADIATION-THERAPY; STRESS-RESPONSE; TUMOR-GROWTH AB Radiotherapy is not currently informed by the genetic composition of an individual patient's tumour. To identify genetic features regulating survival after DNA damage, here we conduct large-scale profiling of cellular survival after exposure to radiation in a diverse collection of 533 genetically annotated human tumour cell lines. We show that sensitivity to radiation is characterized by significant variation across and within lineages. We combine results from our platform with genomic features to identify parameters that predict radiation sensitivity. We identify somatic copy number alterations, gene mutations and the basal expression of individual genes and gene sets that correlate with the radiation survival, revealing new insights into the genetic basis of tumour cellular response to DNA damage. These results demonstrate the diversity of tumour cellular response to ionizing radiation and establish multiple lines of evidence that new genetic features regulating cellular response after DNA damage can be identified. C1 [Yard, Brian D.; Chie, Eui Kyu; Battaglia, Jessica S.; Gopal, Priyanka; Rogacki, Kevin; Phillips, James; Peacock, Craig D.; Abazeed, Mohamed E.] Cleveland Clin, Oncol Res, Dept Translat Hematol, 9500 Euclid Ave R40, Cleveland, OH 44195 USA. [Adams, Drew J.] Case Western Reserve Univ, Dept Genet, 2109 Adelbert Rd BRB, Cleveland, OH 44106 USA. [Chie, Eui Kyu] Seoul Natl Univ, Coll Med, Dept Radiat Oncol, 101 Daehak Ro, Seoul 110774, South Korea. [Tamayo, Pablo; Cheah, Jaime H.; Schreiber, Stuart L.; Hammerman, Peter S.] Broad Inst MIT & Harvard, 415 Main St, Cambridge, MA 02142 USA. [Pearson, Bradley E.; Hammerman, Peter S.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Raymond, Daniel P.] Cleveland Clin, Dept Thorac & Cardiovasc Surg, 9500 Euclid Ave J4-1, Cleveland, OH 44195 USA. [Pennell, Nathan A.] Cleveland Clin, Dept Hematol & Med Oncol, 9500 Euclid Ave R40, Cleveland, OH 44195 USA. [Almeida, Francisco] Cleveland Clin, Dept Pulm Med, 9500 Euclid Ave M2-141, Cleveland, OH 44195 USA. [Cheah, Jaime H.; Clemons, Paul A.; Shamji, Alykhan; Schreiber, Stuart L.] Broad Inst, Ctr Sci Therapeut, 415 Main St, Cambridge, MA 02142 USA. [Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA. [Schreiber, Stuart L.] Broad Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA. [Abazeed, Mohamed E.] Cleveland Clin, Dept Radiat Oncol, 9500 Euclid Ave T2, Cleveland, OH 44195 USA. RP Abazeed, ME (reprint author), Cleveland Clin, Oncol Res, Dept Translat Hematol, 9500 Euclid Ave R40, Cleveland, OH 44195 USA.; Abazeed, ME (reprint author), Cleveland Clin, Dept Radiat Oncol, 9500 Euclid Ave T2, Cleveland, OH 44195 USA. EM abazeem@ccf.org FU NIH [KL2 TR000440]; Radiological Society of North America; Lung Cancer Research Foundation; Free to Breathe; NCI [K08 CA163677]; US National Cancer Institute's Cancer Target Discovery and Development (CTD2) Network [U01 CA176152] FX M.E.A. was supported by NIH KL2 TR000440, the Radiological Society of North America, the Lung Cancer Research Foundation, and Free to Breathe. This publication was made possible in part by the Clinical and Translational Science Collaborative of Cleveland from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. P.S.H. was supported by NCI K08 CA163677. S.L.S. is an Investigator of the Howard Hughes Medical Institute. J.H.C., P.A.C., A.S. and S.L.S. were supported by the US National Cancer Institute's Cancer Target Discovery and Development (CTD2) Network U01 CA176152. The results published here are in whole or part based on data generated by the TCGA Research Network: http://cancergenome.nih.gov/. NR 70 TC 2 Z9 2 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2016 VL 7 AR 11428 DI 10.1038/ncomms11428 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DK1PP UT WOS:000374685600001 PM 27109210 ER PT J AU Mazahery, H Camargo, CA Conlon, C Beck, KL Kruger, MC von Hurst, PR AF Mazahery, Hajar Camargo, Carlos A., Jr. Conlon, Cathryn Beck, Kathryn L. Kruger, Marlena C. von Hurst, Pamela R. TI Vitamin D and Autism Spectrum Disorder: A Literature Review SO NUTRIENTS LA English DT Review DE review; Autism Spectrum Disorder; ASD; Vitamin D; 25(OH)D; intervention; latitude; ethnicity; migration; season; birth; conception ID PERVASIVE DEVELOPMENTAL DISORDERS; NERVE GROWTH-FACTOR; PERINATAL RISK-FACTORS; INCREASED SERUM-LEVELS; DSM-IV-TR; 1,25-DIHYDROXYVITAMIN D-3; D DEFICIENCY; INFANTILE-AUTISM; PRESCHOOL-CHILDREN; OXIDATIVE STRESS AB Low vitamin D status in early development has been hypothesised as an environmental risk factor for Autism Spectrum Disorder (ASD), given the concurrent increase in the prevalence of these two conditions, and the association of vitamin D with many ASD-associated medical conditions. Identification of vitamin D-ASD factors may provide indications for primary and secondary prevention interventions. We systematically reviewed the literature for studies on vitamin D-ASD relationship, including potential mechanistic pathways. We identified seven specific areas, including: latitude, season of conception/birth, maternal migration/ethnicity, vitamin D status of mothers and ASD patients, and vitamin D intervention to prevent and treat ASD. Due to differences in the methodological procedures and inconsistent results, drawing conclusions from the first three areas is difficult. Using a more direct measure of vitamin D status-that is, serum 25(OH) D level during pregnancy or childhood-we found growing evidence for a relationship between vitamin D and ASD. These findings are supported by convincing evidence from experimental studies investigating the mechanistic pathways. However, with few primary and secondary prevention intervention trials, this relationship cannot be determined, unless randomised placebo-controlled trials of vitamin D as a preventive or disease-modifying measure in ASD patients are available. C1 [Mazahery, Hajar; Conlon, Cathryn; Beck, Kathryn L.; Kruger, Marlena C.; von Hurst, Pamela R.] Massey Univ, Inst Food Sci & Technol, Sch Food & Nutr, Palmerston North 4474, New Zealand. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP von Hurst, PR (reprint author), Massey Univ, Inst Food Sci & Technol, Sch Food & Nutr, Palmerston North 4474, New Zealand. EM h.mazahery@hotmail.com; ccamargo@partners.org; c.conlon@massey.ac.nz; k.l.beck@massey.ac.nz; m.c.kruger@massey.ac.nz; P.R.vonHurst@massey.ac.nz OI Camargo, Carlos/0000-0002-5071-7654 NR 199 TC 5 Z9 5 U1 11 U2 17 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD APR PY 2016 VL 8 IS 4 AR 236 DI 10.3390/nu8040236 PG 35 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DK0GH UT WOS:000374590200058 PM 27110819 ER PT J AU Zhang, W Xu, L Cho, SY Min, KJ Oda, T Zhang, LJ Yu, Q Jin, JO AF Zhang, Wei Xu, Li Cho, Si-Young Min, Kyung-Jin Oda, Tatsuya Zhang, LiJun Yu, Qing Jin, Jun-O TI Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis SO NUTRIENTS LA English DT Article DE ginseng berry extract; mouse colitis; intestinal dendritic cell; intestinal macrophage ID INFLAMMATORY-BOWEL-DISEASE; DSS-INDUCED COLITIS; DENDRITIC CELLS; INTESTINAL INFLAMMATION; ULCERATIVE-COLITIS; T-CELLS; MICE; NEUTROPHILS; IMMUNITY; PROMOTE AB This study investigates the in vivo functions of ginseng berry extract (GB) as a therapy for dextran sodium sulfate (DSS)-induced colitis. C57BL/6 mice were given drinking water containing DSS (3%) for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg) once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103(-) CD11c(+) dendritic cells (cDCs), and macrophages. In addition, GB treatment promoted the migration of CD103(+) CD11c(+) cDCs and expansion of Foxp3(+) regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis. C1 [Zhang, Wei; Xu, Li; Zhang, LiJun; Jin, Jun-O] Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai 201508, Peoples R China. [Cho, Si-Young] AmorePacific Corp, R&D Unit, 1920 Yonggudae Ro, Yongin 17074, Gyeonggi Do, South Korea. [Min, Kyung-Jin] Inha Univ, Dept Biol Sci, Inchon 22212, South Korea. [Oda, Tatsuya] Nagasaki Univ, Div Biochem, Fac Fisheries, Nagasaki 55001, Japan. [Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. [Yu, Qing] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Jin, JO (reprint author), Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai 201508, Peoples R China. EM weiwei061215@126.com; wendengxvli@126.com; csy1010@amorepacific.com; minkj@inha.ac.kr; t-oda@nagasaki-u.ac.jp; zhanglijun1221@163.com; Qyu@forsyth.org; junojin1@gmail.com OI Jin, Jun-O/0000-0003-4216-8111 FU Research fund for International Young Scientists from National Natural Science Foundation of China [81550110507]; Major New Drug Discovery Science and Technology [2012ZX09303013]; National Basic Research Program of China (937 Program) [2011CB910702] FX We thank the Shanghai Public Health Clinical Center animal facility for maintaining the animals in this study. This study was supported by Research fund for International Young Scientists from National Natural Science Foundation of China (81550110507). LiJun Zhang was supported by the Major New Drug Discovery Science and Technology (2012ZX09303013) and the National Basic Research Program of China (937 Program) (2011CB910702). NR 59 TC 0 Z9 0 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD APR PY 2016 VL 8 IS 4 AR 199 DI 10.3390/nu8040199 PG 17 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DK0GH UT WOS:000374590200022 PM 27058552 ER PT J AU Ratcliffe, D Doyle, J Sogg, S Rassool, S AF Ratcliffe, Denise Doyle, Jacqueline Sogg, Stephanie Rassool, Sara TI Letter to the Editor: Comment on "The Impact of Psychological Support on Weight Loss Post Weight Loss Surgery: a Randomised Control Trial" SO OBESITY SURGERY LA English DT Letter ID BARIATRIC SURGERY; GASTRIC BYPASS; INTERVENTION; OUTCOMES; OBESITY C1 [Ratcliffe, Denise] Chelsea & Westminster Hosp, Bariatr Surg Serv, London SW10 9NH, England. [Ratcliffe, Denise] CNWL NHS Fdn Trust, Psychol Med Unit, London SW10 9NG, England. [Ratcliffe, Denise] Phoenix Hlth, Chester, Cheshire, England. [Doyle, Jacqueline] Univ Coll London Hosp, NHS Trust, Ctr Weight Management Metab & Endocrine Surg, GI Div, 250 Euston Rd, London NW1 2PG, England. [Sogg, Stephanie] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Sogg, Stephanie] Harvard Univ, Sch Med, Boston, MA USA. [Rassool, Sara] Barts Hlth NHS Trust, Community Hlth Serv Div, Tower Hamlets Adult Weight Management Serv, London, England. [Rassool, Sara] Luton& Dunstable Univ Hosp NHS Trust, Obes & Bariatr Serv, Luton, Beds, England. RP Ratcliffe, D (reprint author), Chelsea & Westminster Hosp, Bariatr Surg Serv, London SW10 9NH, England.; Ratcliffe, D (reprint author), CNWL NHS Fdn Trust, Psychol Med Unit, London SW10 9NG, England.; Ratcliffe, D (reprint author), Phoenix Hlth, Chester, Cheshire, England. EM d.ratcliffe@nhs.net NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 EI 1708-0428 J9 OBES SURG JI Obes. Surg. PD APR PY 2016 VL 26 IS 4 BP 859 EP 860 PG 2 WC Surgery SC Surgery GA DJ7PD UT WOS:000374402400028 PM 26755181 ER PT J AU Mulla, CM Storino, A Yee, EU Lautz, D Sawnhey, MS Moser, AJ Patti, ME AF Mulla, Christopher M. Storino, Alessandra Yee, Eric U. Lautz, David Sawnhey, Mandeep S. Moser, A. James Patti, Mary-Elizabeth TI Insulinoma After Bariatric Surgery: Diagnostic Dilemma and Therapeutic Approaches SO OBESITY SURGERY LA English DT Review DE Insulinoma; Bariatric surgery; Hypoglycemia; Gastric bypass; Minimally invasive surgery ID GASTRIC-BYPASS-SURGERY; HYPERINSULINEMIC HYPOGLYCEMIA; PANCREATIC INSULINOMAS; GLUCOSE-TOLERANCE; FUNCTIONING INSULINOMA; DISTAL PANCREATECTOMY; SLEEVE GASTRECTOMY; MANAGEMENT; NEUROGLYCOPENIA; EXPERIENCE AB Hypoglycemia is increasingly recognized as a complication of bariatric surgery. Typically, hypoglycemia does not appear immediately postoperatively, but rather more than 1 year later, and usually occurs 1-3 h after meals. While rare, insulinoma has been reported after bariatric surgery. Clinical factors which should raise suspicion for insulinoma and the need for comprehensive clinical and biochemical evaluation include hypoglycemia occurring in the fasting state, predating bariatric surgery, and/or worsening immediately postoperatively, and lack of response to conservative therapy. Localization and successful resection of insulinoma can be achieved using novel endoscopic ultrasound and surgical approaches. In summary, hypoglycemia presenting shortly after gastric bypass or with a dominant fasting pattern should be fully evaluated to exclude insulinoma. Additionally, evaluation prior to gastric bypass should include screening for history of hypoglycemia symptoms. C1 [Mulla, Christopher M.; Patti, Mary-Elizabeth] Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. [Mulla, Christopher M.; Patti, Mary-Elizabeth] Joslin Diabet Ctr, Clin Div, 1 Joslin Pl, Boston, MA 02215 USA. [Mulla, Christopher M.; Patti, Mary-Elizabeth] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA. [Mulla, Christopher M.; Storino, Alessandra; Yee, Eric U.; Lautz, David; Sawnhey, Mandeep S.; Moser, A. James; Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. [Storino, Alessandra; Moser, A. James] Beth Israel Deaconess Med Ctr, Pancreas & Liver Inst, Boston, MA 02215 USA. [Storino, Alessandra; Moser, A. James] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Yee, Eric U.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Lautz, David] Emerson Hosp, Dept Surg, Concord, MA USA. [Lautz, David] Massachusetts Gen Hosp, Concord, MA USA. [Sawnhey, Mandeep S.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gastroenterol, Boston, MA 02215 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA.; Patti, ME (reprint author), Joslin Diabet Ctr, Clin Div, 1 Joslin Pl, Boston, MA 02215 USA.; Patti, ME (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA.; Patti, ME (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM mary.elizabeth.patti@joslin.harvard.edu OI Yee, Eric/0000-0001-9643-6439 FU NIH [T32 DK007260, P30 DK036836] FX We gratefully acknowledge grant support from NIH T32 DK007260 (to CMM) and NIH P30 DK036836 (Diabetes Research Center, Joslin). NR 49 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 EI 1708-0428 J9 OBES SURG JI Obes. Surg. PD APR PY 2016 VL 26 IS 4 BP 874 EP 881 DI 10.1007/s11695-016-2092-5 PG 8 WC Surgery SC Surgery GA DJ7PD UT WOS:000374402400034 PM 26846121 ER PT J AU LaPrade, RF Agel, J Baker, J Brenner, JS Cordasco, FA Cote, J Engebretsen, L Feeley, BT Gould, D Hainline, B Hewett, T Jayanthi, N Kocher, MS Myer, GD Nissen, CW Philippon, MJ Provencher, MT AF LaPrade, Robert F. Agel, Julie Baker, Joseph Brenner, Joel S. Cordasco, Frank A. Cote, Jean Engebretsen, Lars Feeley, Brian T. Gould, Daniel Hainline, Brian Hewett, Timothy Jayanthi, Neeru Kocher, Mininder S. Myer, Gregory D. Nissen, Carl W. Philippon, Marc J. Provencher, Matthew T. TI AOSSM Early Sport Specialization Consensus Statement SO ORTHOPAEDIC JOURNAL OF SPORTS MEDICINE LA English DT Article DE early sports specialization; consensus; youth sports ID JUNIOR TENNIS PLAYERS; DELIBERATE PRACTICE; YOUTH SPORT; BURNOUT; EXPERTISE; TALENT AB Background: Early sport specialization is not a requirement for success at the highest levels of competition and is believed to be unhealthy physically and mentally for young athletes. It also discourages unstructured free play, which has many benefits. Purpose: To review the available evidence on early sports specialization and identify areas where scientific data are lacking. Study Design: Think tank, roundtable discussion. Results: The primary outcome of this think tank was that there is no evidence that young children will benefit from early sport specialization in the majority of sports. They are subject to overuse injury and burnout from concentrated activity. Early multisport participation will not deter young athletes from long-term competitive athletic success. Conclusion: Youth advocates, parents, clinicians, and coaches need to work together with the sport governing bodies to ensure healthy environments for play and competition that do not create long-term health issues yet support athletic competition at the highest level desired. C1 [Agel, Julie] Box 359798,325 Ninth Ave, Seattle, WA 98104 USA. [LaPrade, Robert F.] Steadman Philippon Res Inst, Vail, CO USA. [Agel, Julie] Univ Washington, Harborview Med Ctr, 325 9Th Ave, Seattle, WA 98104 USA. [Baker, Joseph] York Univ, York Univ Ctr Aging Res & Educ, Sch Kinesiol & Hlth Sci, Toronto, ON M3J 2R7, Canada. [Brenner, Joel S.] Childrens Hosp Kings Daughters, Sports Med Program, Norfolk, VA USA. [Brenner, Joel S.] Eastern Virginia Med Sch, Div Sports Med & Adolescent Med, Norfolk, VA 23501 USA. [Brenner, Joel S.] Eastern Virginia Med Sch, Pediat, Norfolk, VA 23501 USA. [Cordasco, Frank A.] Cornell Univ, Weill Cornell Med Coll, Orthopaed Surg, New York, NY 10021 USA. [Cordasco, Frank A.] Hosp Special Surg, Sports Med & Shoulder Serv, 535 E 70th St, New York, NY 10021 USA. [Cordasco, Frank A.] Hosp Special Surg, Leon Root Mot Anal Lab, 535 E 70th St, New York, NY 10021 USA. [Cote, Jean] Queens Univ, Sch Kinesiol & Hlth Studies, Kingston, ON, Canada. [Engebretsen, Lars] Int Olymp Comm, Med & Sci Dept, Lausanne, Switzerland. [Engebretsen, Lars] Norwegian Sch Sport Sci, Dept Sports Med, Oslo Sports Trauma Res Ctr, Oslo, Norway. [Engebretsen, Lars] Oslo Univ Hosp, Dept Orthoped Surg, N-0450 Oslo, Norway. [Feeley, Brian T.] Univ Calif San Francisco, Dept Orthopaed Surg, Sports Med, San Francisco, CA 94143 USA. [Gould, Daniel] Michigan State Univ, Dept Kinesiol, Coll Educ, Inst Study Youth Sports, E Lansing, MI 48824 USA. [Hainline, Brian] Indiana Univ Sch Med, Neurol, Indianapolis, IN 46202 USA. [Hainline, Brian] NYU, Sch Med, New York, NY USA. [Hewett, Timothy] Mayo Clin, Orthopaed Surg, Rochester, MN USA. [Hewett, Timothy] Mayo Clin, Sports Med Res, Biomech, Rochester, MN USA. [Hewett, Timothy] Mayo Clin, Orthopaed Surg Phys Med & Rehabil, Physiol & Biomed Engn, Rochester, MN USA. [Jayanthi, Neeru] Emory Sports Med Ctr, Orthoped & Family Med, Atlanta, GA USA. [Jayanthi, Neeru] Emory Sports Med Ctr, Tennis Med, Atlanta, GA USA. [Jayanthi, Neeru] Emory Sports Med Ctr, Primary Care Sports Med Fellowship, Atlanta, GA USA. [Kocher, Mininder S.] Harvard Univ, Sch Med, Orthopaed Surg, Boston, MA USA. [Kocher, Mininder S.] Boston Childrens Hosp, Div Sports Med, Boston, MA USA. [Myer, Gregory D.] Cincinnati Childrens Hosp Med Ctr, Div Sports Med 1, Res & Human Performance Lab, Cincinnati, OH 45229 USA. [Myer, Gregory D.] Univ Cincinnati, Dept Pediat & Orthopaed Surg, Cincinnati, OH USA. [Myer, Gregory D.] Micheli Ctr Sports Injury Prevent, Waltham, MA USA. [Myer, Gregory D.] Univ Penn, Dept Orthopaed, Philadelphia, PA 19104 USA. [Nissen, Carl W.] Connecticut Childrens Med Ctr, Elite Sports Med, Farmington, CT USA. [Nissen, Carl W.] Univ Connecticut, Dept Orthopaed, Storrs, CT USA. [Nissen, Carl W.] Trinity Coll, Team Physician, Hartford, CT 06106 USA. [Philippon, Marc J.] Steadman Clin, Managing Partner, Vail, CO USA. [Philippon, Marc J.] Steadman Philippon Res Inst, Vail, CO USA. [Philippon, Marc J.] Sports Med Program, Steadman Philippon Res Inst, Vail, CO USA. [Philippon, Marc J.] Univ Pittsburgh, Dept Orthopaed Surg, Pittsburgh, PA USA. [Provencher, Matthew T.] Massachusetts Gen Hosp, Sports Med & Surg, Boston, MA 02114 USA. [Provencher, Matthew T.] New England Patriots, Boston, MA USA. [Provencher, Matthew T.] Univ Hlth Sci, Uniformed Serv, Surg, Bethesda, MD USA. [Provencher, Matthew T.] Harvard Univ, Boston, MA 02115 USA. RP Agel, J (reprint author), Box 359798,325 Ninth Ave, Seattle, WA 98104 USA. EM bagel@uw.edu RI Myer, Gregory/H-6572-2016 OI Myer, Gregory/0000-0002-9983-8422 NR 44 TC 2 Z9 2 U1 17 U2 22 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2325-9671 J9 ORTHOP J SPORTS MED JI Orthop. J. Sports Med. PD APR PY 2016 VL 4 IS 4 AR 2325967116644241 DI 10.1177/2325967116644241 PG 8 WC Sport Sciences SC Sport Sciences GA DL6AN UT WOS:000375719200009 PM 27169132 ER PT J AU Arnstein, P Broglio, K AF Arnstein, Paul Broglio, Kathleen TI Tapentadol Therapy to Manage Moderate-to-Severe Pain: Key Considerations for Nursing SO PAIN MANAGEMENT NURSING LA English DT Meeting Abstract C1 [Arnstein, Paul] Massachusetts Gen Hosp, Pain Relief, Boston, MA 02114 USA. [Broglio, Kathleen] Columbia Univ, Ambulatory Palliat Care Serv, Med Ctr, New York, NY 10027 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 1524-9042 EI 1532-8635 J9 PAIN MANAG NURS JI Pain Manag. Nurs. PD APR PY 2016 VL 17 IS 2 BP 98 EP 98 PG 1 WC Nursing SC Nursing GA DL4EO UT WOS:000375586600022 ER PT J AU Haas, RLM Miah, AB LePechoux, C DeLaney, TF Baldini, EH Alektiar, K O'Sullivan, B AF Haas, Rick L. M. Miah, Aisha B. LePechoux, Cecile DeLaney, Thomas F. Baldini, Elizabeth H. Alektiar, Kaled O'Sullivan, Brian TI Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies SO RADIOTHERAPY AND ONCOLOGY LA English DT Review DE Limb Soft Tissue Sarcoma; Surgery; Preoperative radiotherapy; Combined modality treatment; Targeted agents; Chemotherapy ID INDUCED PATHOLOGICAL NECROSIS; MODULATED RADIATION-THERAPY; EXCELLENT LOCAL-CONTROL; LIMB-SPARING SURGERY; PHASE-I TRIAL; HIGH-RISK; NEOADJUVANT CHEMOTHERAPY; HIGH-GRADE; ADJUVANT CHEMOTHERAPY; FOLLOW-UP AB Introduction: This critical review aims to summarize published data on limb sparing surgery for extremity soft tissue sarcoma in combination with pre-operative radiotherapy (RT). Methods: This review is based on peer-reviewed publications using a PubMed search on the MeSH headings "soft tissue sarcoma" AND "preoperative radiotherapy". Titles and abstracts screened for data including "fraction size AND/OR total dose AND/OR overall treatment time", "chemotherapy", "targeted agents AND/OR tyrosine kinase inhibitors", are collated. Reference lists from some articles have been studied to obtain other pertinent articles. Additional abstracts presented at international sarcoma meetings have been included as well as information on relevant clinical trials available at the ClinicalTrials.gov website. Results: Data are presented for the conventional regimen of 50-50.4 Gy in 25-28 fractions in 5-6 of weeks preoperative external beam RT with respect to the regimen's local control probability compared to surgery alone, as well as acute and late toxicities. The rationale and outcome data for hypofractionated and/or reduced dose regimens are discussed. Finally, combination schedules with conventional chemotherapy and/or targeted agents are summarized. Conclusion: Outside the setting of well-designed prospective clinical trials, the conventional 50 Gy in 5-6 week schedule should be considered as standard. However, current and future studies addressing alternative fraction size, total dose, overall treatment time and/or combination with chemotherapy or targeted agents may reveal regimens of equal or increased efficacy with reduced late morbidities. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Haas, Rick L. M.] Netherlands Canc Inst, Dept Radiotherapy, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. [Miah, Aisha B.] Royal Marsden Hosp, Dept Radiotherapy & Phys, Sarcoma Unit, London SW3 6JJ, England. [LePechoux, Cecile] Gustave Roussy, Dept Radiat Oncol, Paris, France. [DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Baldini, Elizabeth H.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Baldini, Elizabeth H.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Alektiar, Kaled] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY USA. [O'Sullivan, Brian] Univ Toronto, Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M5S 1A1, Canada. RP Haas, RLM (reprint author), Netherlands Canc Inst, Dept Radiotherapy, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. EM r.haas@nki.nl NR 72 TC 0 Z9 0 U1 1 U2 3 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 APR PY 2016 VL 119 IS 1 BP 14 EP 21 DI 10.1016/j.radonc.2015.12.002 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DL7LR UT WOS:000375822700004 PM 26718153 ER PT J AU Chowdhry, VK Liu, L Goldberg, S Adams, JA Bernstein, KD Liebsch, NJ Niemierko, A Chen, YL DeLaney, TF AF Chowdhry, Varun K. Liu, Li Goldberg, Saveli Adams, Judith A. Bernstein, Karen De Amorim Liebsch, Norbert J. Niemierko, Andrzej Chen, Yen-Lin DeLaney, Thomas F. TI Thoracolumbar spinal cord tolerance to high dose conformal proton-photon radiation therapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Late-effects; Spinal cord tolerance; Sarcoma; Chordoma; Chondrosarcoma ID NON-HODGKINS-LYMPHOMA; NORMAL TISSUE; RADIOTHERAPY; IRRADIATION; MYELOPATHY; MYELITIS; TRANSPLANTATION; REIRRADIATION; SIGN AB Purpose: To evaluate and understand the tolerance of the thoracolumbar spinal cord using equivalent uniform dose (EUD) and dose volume histogram (DVH) analysis after combined high dose photon-proton radiotherapy. Materials and methods: A total of 68 patients were identified as having high dose radiotherapy, >= 5900 cGy (RBE) in the region of the thoracolumbar spinal cord, defined as extending inferiorly to L2. Pathological diagnosis for patients in this review included chordoma (50 patients, 53.1%), chondrosarcoma (28 patients, 29.8%), osteosarcoma (3 patients, 3.2%), other sarcoma (11 patients, 11.7%), and other (2 patients, 2.1%). Patient data were reviewed retrospectively, detailed dose volume histogram data (DVH) were available for 23 patients. Composite plans and DVH were constructed for both preoperative and post-operative radiation therapy courses in MIM-Vista software, as available. Dose constraints to the center and surface of the cord were 5400 cGy (RBE), and 6300 cGy (RBE) respectively, and patients receiving concurrent chemotherapy received an eight percent dose reduction. Spinal cord toxicity was recorded using the RTOG/EORTC late effects scoring system. Results: Clinical and dosimetric data for each patient were analyzed. Median prescription dose was 7020 cGy (RBE), range (5940-7820 cGy (RBE)). Median follow-up was 12.9 months. Five-year overall survival for all patients in this group was 88.7%, 95%CI (74.7-95.2). One patient suffered from transient paralysis following stem cell transplant for treatment of myelodysplastic syndrome. Other reasons for spinal cord injury following treatment included: local disease progression, noted in 7 patients (10.3%), and direct result of surgery, noted in 8 patients (11.8%). Freedom from neurological injury (RTOG Grade 2 or higher) at 5 years was 92.9%(95%CI: 74.6-98.2), at 6 years was 80.9%(95%CI: 55.3-92.7), and at 8 years 80.9%(95%CI: 55.3-92.7). Conclusion: Our clinical and dosimetric data suggest that the noted dose constraints are safe and acceptable with regard to spinal cord complications. Pre-existing disease characteristics, surgical complications, as well as tumor progression, appear to be more important factors when it comes to spinal cord toxicity. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Chowdhry, Varun K.] Univ Rochester, Dept Radiat Oncol, Hornell, NY USA. [Liu, Li; Goldberg, Saveli; Adams, Judith A.; Bernstein, Karen De Amorim; Liebsch, Norbert J.; Niemierko, Andrzej; Chen, Yen-Lin; DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Chowdhry, VK (reprint author), Univ Rochester, Med Ctr, 21 Orchard St, Hornell, NY 14843 USA. EM Varun_Chowdhry@urmc.rochester.edu NR 19 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2016 VL 119 IS 1 BP 35 EP 39 DI 10.1016/j.radonc.2016.01.002 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DL7LR UT WOS:000375822700007 PM 26791929 ER PT J AU Kopacz, MS Nieuwsma, JA Jackson, GL Rhodes, JE Cantrell, WC Bates, MJ Meador, KG AF Kopacz, Marek S. Nieuwsma, Jason A. Jackson, George L. Rhodes, Jeffrey E. Cantrell, William C. Bates, Mark J. Meador, Keith G. TI Chaplains' Engagement with Suicidality among Their Service Users: Findings from the VA/DoD Integrated Mental Health Strategy SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID UNITED-STATES; ACTIVE-DUTY; VETERANS; RISK; ATTENDANCE; PERSONNEL; CHURCH; CARE AB Chaplains play an important role in supporting the mental health of current and former military personnel; in this study, the engagement of Department of Veterans Affairs (VA), Army, Navy, and Air Force chaplains with suicidality among their service users were examined. An online survey was used to collect data from 440 VA and 1,723 Department of Defense (DoD) chaplains as part of the VA/DoD Integrated Mental Health Strategy. Differences were noted for demographics, work setting characteristics, encountering suicidality, and self-perceived preparation for dealing with suicidality. Compared to DoD chaplains, VA chaplains encounter more at-risk service users, yet feel less prepared for dealing with suicidality. C1 [Kopacz, Marek S.] US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. [Nieuwsma, Jason A.; Cantrell, William C.; Meador, Keith G.] Mid Atlantic Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Mental Hlth & Chaplaincy, Durham, NC USA. [Nieuwsma, Jason A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Jackson, George L.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Jackson, George L.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. [Rhodes, Jeffrey E.; Bates, Mark J.] Def Ctr Excellence Psychol Hlth & Traumat Brain I, Deployment Hlth Clin Ctr, Psychol Hlth Promot, Silver Spring, MD USA. [Meador, Keith G.] Vanderbilt Univ, Ctr Biomed Eth & Soc, Dept Psychiat, 221 Kirkland Hall, Nashville, TN 37235 USA. [Meador, Keith G.] Vanderbilt Univ, Ctr Biomed Eth & Soc, Dept Hlth Policy, 221 Kirkland Hall, Nashville, TN 37235 USA. [Meador, Keith G.] Vanderbilt Univ, Grad Dept Relig, 221 Kirkland Hall, Nashville, TN 37235 USA. RP Kopacz, MS (reprint author), US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. EM marek.kopacz@va.gov FU VISN 2 Center of Excellence for Suicide Prevention in Canandaigua, New York FX The views expressed are those of the authors and do not reflect the official policy or position of the US Department of Veterans Affairs, the US Department of Defense, or the US Government. This work was funded, in part, by the VISN 2 Center of Excellence for Suicide Prevention in Canandaigua, New York. NR 23 TC 2 Z9 2 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD APR PY 2016 VL 46 IS 2 BP 206 EP 212 DI 10.1111/sltb.12184 PG 7 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DK1TC UT WOS:000374696200007 PM 26255592 ER PT J AU Amini, AR Xu, TO Chidambaram, RM Nukavarapu, SP AF Amini, Ami R. Xu, Thomas O. Chidambaram, Ramaswamy M. Nukavarapu, Syam P. TI Oxygen Tension-Controlled Matrices with Osteogenic and Vasculogenic Cells for Vascularized Bone Regeneration In Vivo SO TISSUE ENGINEERING PART A LA English DT Article ID ENDOTHELIAL PROGENITOR CELLS; MESENCHYMAL STEM-CELLS; TISSUE-ENGINEERED BONE; UMBILICAL-CORD BLOOD; PERIPHERAL-BLOOD; GROWTH-FACTOR; SCAFFOLDS; ANGIOGENESIS; CHALLENGES; DIFFERENTIATION AB Despite recent progress, segmental bone defect repair is still a significant challenge in orthopedic surgery. While bone tissue engineering approaches using biodegradable matrices along with bone/blood vessel forming cells offered improved possibilities, current regenerative strategies lack the ability to achieve vascularized bone regeneration in critical-sized/segmental bone defects. In this study, we introduced and evaluated a two-pronged approach for vascularized bone regeneration in vivo. The goal was to demonstrate vascularized bone formation using oxygen tension-controlled (OTC) matrices seeded with bone and blood vessel forming cells. OTC matrices were coimplanted with rabbit mesenchymal stem cells (MSCs) and peripheral blood-derived endothelial progenitor cells (PB-EPCs) to demonstrate the osteogenic and vasculogenic differentiation of these cells, postseeding on a matrix, especially deep inside the matrix pore structure. Matrices coimplanted with varied rabbit MSC and PB-EPC ratios (1:4, 1:1, and 4:1) were assessed in a nude mouse subcutaneous implantation model to determine a coimplantation ratio with superior osteogenic as well as vasculogenic properties. The implants were analyzed, at week 8, for endothelial (CD31 and Von Willebrand factor [vWF]) and osteogenic marker (RunX2 and Col I) staining qualitatively and collagen deposition and number of vessel formation quantitatively. Results from these experiments established MSC-to-PB-EPC ratio 1:1 as the best coimplantation ratio. OTC matrix with 1:1 coimplantation ratio was assessed for segmental bone defect repair in a rabbit critical-sized bone defect model. The group under investigation was OTC matrix, and the matrix was seeded with MSCs, EPCs, or MSCs:EPCs in a 1:1 ratio. Explants at week 12 were evaluated for bone defect repair via micro-CT and histology. Results from rabbit in vivo experiments show enhanced mineralization and vascularization for the 1:1 coimplantation group. Overall, the study establishes a two-pronged approach involving OTC matrix and effective progenitors for large-area and vascularized bone regeneration. C1 [Amini, Ami R.] Massachusetts Gen Hosp, Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Xu, Thomas O.; Nukavarapu, Syam P.] Univ Connecticut, Ctr Hlth, Inst Regenerat Engn, Farmington, CT USA. [Xu, Thomas O.; Nukavarapu, Syam P.] Univ Connecticut, Ctr Hlth, Dept Orthoped Surg, Farmington, CT 06030 USA. [Chidambaram, Ramaswamy M.] Univ Connecticut, Ctr Hlth, Ctr Comparat Med, Farmington, CT USA. [Nukavarapu, Syam P.] Univ Connecticut, Dept Mat Sci & Engn, Storrs, CT USA. [Nukavarapu, Syam P.] Univ Connecticut, Dept Biomed Engn, Storrs, CT USA. RP Nukavarapu, SP (reprint author), Univ Connecticut, Ctr Hlth, Dept Orthoped Surg, Farmington, CT 06030 USA. EM syam@uchc.ed FU AO Foundation [S-13-122N]; Musculoskeletal Transplant Foundation (MTF); NSF (EFRI) [1332329]; NIH (BUILD) [8RL5GM118969]; Connecticut Institute for Clinical and Translational Science (CICATS) at the University of Connecticut; NIH [F30DE022477] FX Dr. Nukavarapu acknowledges funding from the AO Foundation (startup grant: S-13-122N). The authors acknowledge support from the Musculoskeletal Transplant Foundation (MTF), NSF (EFRI# 1332329), NIH (BUILD# 8RL5GM118969), and Connecticut Institute for Clinical and Translational Science (CICATS) at the University of Connecticut. Ms. A.R.A. thank NIH F30DE022477 award for financial support. The authors thank Dr. Adams and Vilmaris Diaz-Doran for their help with the micro-CT work. NR 52 TC 0 Z9 0 U1 4 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD APR PY 2016 VL 22 IS 7-8 BP 610 EP 620 DI 10.1089/ten.tea.2015.0310 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA DK2RH UT WOS:000374761600004 PM 26914219 ER PT J AU Lee, SR Kilcoyne, A Kambadakone, A Arellano, R AF Lee, Stephen R. Kilcoyne, Aoife Kambadakone, Avinash Arellano, Ronald TI Interventional oncology: pictorial review of post-ablation imaging of liver and renal tumors SO ABDOMINAL RADIOLOGY LA English DT Article DE Interventional oncology; Ablation; Hepatocellular carcinoma; Renal cell carcinoma; Post-ablation imaging ID PERCUTANEOUS RADIOFREQUENCY ABLATION; HEPATOCELLULAR-CARCINOMA; IRREVERSIBLE ELECTROPORATION; HEPATIC-TUMORS; CELL CARCINOMA; CRYOSURGERY INCREASES; MICROWAVE ABLATION; COMPLICATION RATE; THERMAL ABLATION; ENHANCED MRI AB Percutaneous image-guided ablation is now commonly performed in many institutions for the treatment of hepatocellular carcinoma, liver metastases, and renal cell carcinoma in select patients. Accurate interpretation of post-ablation imaging is of supreme importance because treatment algorithms for these diseases rely heavily on imaging to guide management decisions. The purpose of this pictorial essay is to provide abdominal imagers with a review of the indications for percutaneous ablation in the abdomen, a basic overview of ablation modalities in clinical use today, the expected post-ablation imaging findings in the liver and kidney, and potential complications of hepatic and renal ablation procedures. C1 [Lee, Stephen R.; Kilcoyne, Aoife; Kambadakone, Avinash; Arellano, Ronald] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, White Bldg,Rm 270,55 Fruit St, Boston, MA 02114 USA. RP Lee, SR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, White Bldg,Rm 270,55 Fruit St, Boston, MA 02114 USA. EM slee112@partners.org FU Mac Erlaine Scholarship, from the Academic Radiology Research Trust, St. Vincent's Radiology Group, Dublin, Ireland FX Aoife Kilcoyne would like to acknowledge the support of the Mac Erlaine Scholarship, from the Academic Radiology Research Trust, St. Vincent's Radiology Group, Dublin, Ireland. NR 79 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD APR PY 2016 VL 41 IS 4 BP 677 EP 705 DI 10.1007/s00261-016-0665-3 PG 29 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DK5MN UT WOS:000374964100013 PM 26934894 ER PT J AU Masch, WR Kamaya, A Wasnik, AP Maturen, KE AF Masch, William R. Kamaya, Aya Wasnik, Ashish P. Maturen, Katherine E. TI Ovarian cancer mimics: how to avoid being fooled by extraovarian pelvic masses SO ABDOMINAL RADIOLOGY LA English DT Article DE Ovarian cancer; Adnexal masses; Cancer mimics; Ovarian malignancy; Gynecologic oncology ID ADNEXAL MASSES; TUMORS; CARCINOMATOSIS; LYMPHOMA; AFIP; CT AB In our clinical experience, pelvic masses from a variety of anatomic sites may be misdiagnosed as ovarian cancer. This tendency to overdiagnose a rare disease probably reflects both its protean imaging appearance and concern for its potential morbidity and mortality. However, radiologists can better serve patients with an analytic approach to the anatomic and tissue features of pelvic masses. We review a range of ovarian cancer mimics and illustrate the radiologic reasoning enabling correct diagnosis. C1 [Masch, William R.] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. [Kamaya, Aya] Stanford Univ, Med Ctr, Dept Radiol, 300 Pasteur Dr,H1307 MC 5621, Stanford, CA 94305 USA. [Wasnik, Ashish P.; Maturen, Katherine E.] Univ Michigan Hosp, Dept Radiol, 1500 E Med Ctr Dr UH B1D530, Ann Arbor, MI 48109 USA. RP Maturen, KE (reprint author), Univ Michigan Hosp, Dept Radiol, 1500 E Med Ctr Dr UH B1D530, Ann Arbor, MI 48109 USA. EM kmaturen@umich.edu NR 25 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD APR PY 2016 VL 41 IS 4 BP 783 EP 793 DI 10.1007/s00261-015-0570-1 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DK5MN UT WOS:000374964100020 PM 26867729 ER PT J AU Albrecht, DS Granziera, C Hooker, JM Loggia, ML AF Albrecht, Daniel S. Granziera, Cristina Hooker, Jacob M. Loggia, Marco L. TI In Vivo Imaging of Human Neuroinflammation SO ACS CHEMICAL NEUROSCIENCE LA English DT Review DE Neuroimmunology; microglia; astrocyte; blood-brain barrier; brain imaging; MRS ID BLOOD-BRAIN-BARRIER; PROTEIN 18 KDA; POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE-SPECTROSCOPY; SELECTIVE NEURONAL LOSS; CENTRAL-NERVOUS-SYSTEM; REGIONAL PAIN SYNDROME; TRANSLOCATOR PROTEIN; MULTIPLE-SCLEROSIS; BENZODIAZEPINE-RECEPTOR AB Neuroinflammation is implicated in the pathophysiology of a growing number of human disorders, including multiple sclerosis, chronic pain, traumatic brain injury, and amyotrophic lateral sclerosis. As a result, interest in the development of novel methods to investigate neuroinflammatory processes, for the purpose of diagnosis, development of new therapies, and treatment monitoring, has surged over the past 15 years. Neuroimaging offers a wide array of non- or minimally invasive techniques to characterize neuroinflammatory processes. The intent of this Review is to provide brief descriptions of currently available neuroimaging methods to image neuroinflammation in the human central nervous system (CNS) in vivo. Specifically, because of the relatively widespread accessibility of equipment for nuclear imaging (positron emission tomography [PET]; single photon emission computed tomography [SPECT]) and magnetic resonance imaging (MRI), we will focus on strategies utilizing these technologies. We first provide a working definition of "neuroinflammation" and then discuss available neuroimaging methods to study human neuroinflammatory processes. Specifically, we will focus on neuroimaging methods that target (1) the activation of CNS immunocompetent cells (e.g. imaging of glial activation with TSPO tracer [C-11]PBR28), (2) compromised BBB (e.g. identification of MS lesions with gadolinium enhanced MRI), (3) CNS-infiltration of circulating immune cells (e.g. tracking monocyte infiltration into brain parenchyma with iron oxide nanoparticles and MRI), and (4) pathological consequences of neuroinflammation (e.g. imaging apoptosis with [Tc-99m]Annexin V or iron accumulation with T2* relaxometry). This Review provides an overview of state-of-the-art techniques for imaging human neuroinflammation which have potential to impact patient care in the foreseeable future. C1 [Albrecht, Daniel S.; Granziera, Cristina; Hooker, Jacob M.; Loggia, Marco L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,MGH MIT HMS Athinoula A Martinos Ctr, Boston, MA 02129 USA. [Albrecht, Daniel S.] Massachusetts Gen Hosp, Dept Radiol, Gordon Ctr Med Imaging, NMMI, Boston, MA 02114 USA. [Albrecht, Daniel S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Granziera, Cristina] CHU Vaudois, Dept Clin Neurosci, Div Neurol, Neuroimmunol, CH-1011 Lausanne, Switzerland. [Granziera, Cristina] Univ Lausanne, CH-1011 Lausanne, Switzerland. [Granziera, Cristina] Ecole Polytech Fed Lausanne, LTSS, CH-1015 Lausanne, Switzerland. RP Albrecht, DS (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 Thirteenth St,Room 2301, Charlestown, MA 02129 USA. EM dsalbrecht@mgh.harvard.edu OI Granziera, Cristina/0000-0002-4917-8761 FU DoD [W81XWH-14-1-0543]; [5T32EB13180]; [1R21NS087472-01A1] FX We would like to acknowledge the following funding mechanisms for support of this project: 5T32EB13180 (T32 supporting D.S.A.), 1R21NS087472-01A1 (M.L.L.), and DoD W81XWH-14-1-0543 (M.L.L.). NR 142 TC 3 Z9 3 U1 9 U2 33 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD APR PY 2016 VL 7 IS 4 BP 470 EP 483 DI 10.1021/acschemneuro.6b00056 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA DK3JG UT WOS:000374812300009 PM 26985861 ER PT J AU Wang, CN Placzek, MS Van de Bittner, GC Schroeder, FA Hooker, JM AF Wang, Changning Placzek, Michael S. Van de Bittner, Genevieve C. Schroeder, Frederick A. Hooker, Jacob M. TI A Novel Radiotracer for Imaging Monoacylglycerol Lipase in the Brain Using Positron Emission Tomography SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Monoacylglycerol lipase; PET; radiotracer; brain; CNS ID RAT CEREBELLAR MEMBRANES; ENDOCANNABINOID SYSTEM; SELECTIVE BLOCKADE; ENERGY-BALANCE; HYDROLYSIS; 2-ARACHIDONOYLGLYCEROL; INHIBITORS; METABOLISM; MECHANISMS; PAIN AB Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerols to glycerol and fatty acid and plays an important role in neuroinflammation. MAGL inhibitors are a class of molecules with therapeutic potential for human diseases of the central nervous system (CNS), in areas such as pain and inflammation, immunological disorders, and neurological and psychiatric conditions. Development of a noninvasive imaging probe would elucidate the distribution and functional roles of MAGL in the brain and accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and pilot rodent imaging of a novel MAGL imaging agent, [C-11]SAR127303. Our imaging results demonstrate the high specificity, good selectivity, and appropriate kinetics and distribution of [C-11]SAR127303, validating its utility for imaging MAGL in the brain. Our findings support the translational potential for human CNS MAGL imaging. C1 [Wang, Changning; Placzek, Michael S.; Van de Bittner, Genevieve C.; Schroeder, Frederick A.; Hooker, Jacob M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Placzek, Michael S.] Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat,McLean Imaging Ctr, Belmont, MA 02478 USA. RP Wang, CN (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, CNY 149,Room 5-022A,149 13th St, Charlestown, MA 02179 USA. EM cwang15@mgh.harvard.edu FU Harvard/MGH Nuclear Medicine Training Program from the Department of Energy [DE-SC0008430]; NIH-NIDA T32 postdoctoral fellowship [T32DA015036]; Center for Functional Neuroimaging Technologies [P41EB015896]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health; NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; [S10RR015728] FX This research was supported by the Harvard/MGH Nuclear Medicine Training Program from the Department of Energy under Grant DE-SC0008430 (C.W. and G.C.V.d.B.) and NIH-NIDA T32 postdoctoral fellowship T32DA015036 (M.S.P.). This research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Regional Resource supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, Grant Number: S10RR015728. NR 26 TC 4 Z9 4 U1 4 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD APR PY 2016 VL 7 IS 4 BP 484 EP 489 DI 10.1021/acschemneuro.5b00293 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA DK3JG UT WOS:000374812300010 PM 26694017 ER PT J AU Min, JH Choi, KY Dreaden, EC Padera, RF Braatz, RD Spector, M Hammond, PT AF Min, Jouha Choi, Ki Young Dreaden, Erik C. Padera, Robert F. Braatz, Richard D. Spector, Myron Hammond, Paula T. TI Designer Dual Therapy Nanolayered Implant Coatings Eradicate Biofilms and Accelerate Bone Tissue Repair SO ACS NANO LA English DT Article DE antibacterial; regenerative medicine; nanolayered coating; layer-by-layer; controlled drug release; biomaterials; wound healing ID TOTAL HIP-ARTHROPLASTY; UNITED-STATES; IN-VIVO; INFECTIONS; OSTEOMYELITIS; REVISION; GROWTH; INTEGRATION; PROTEINS; CEMENT AB Infections associated with orthopedic implants cause increased morbidity and significant healthcare cost. A prolonged and expensive two-stage procedure requiring two surgical steps and a 6-8 week period of joint immobilization exists as today's gold standard for the revision arthroplasty of an infected prosthesis. Because infection is much more common in implant replacement surgeries, these issues greatly impact long-term patient care for a continually growing part of the population. Here, we demonstrate that a single-stage revision using prostheses coated with self-assembled, hydrolytically degradable multi layers that sequentially deliver the antibiotic (gentamicin) and the osteoinductive growth factor (BMP-2) in a time staggered manner enables both eradication of established biofilms and complete and rapid bone tissue repair around the implant in rats with induced osteomyelitis. The nanolayered construct allows precise independent control of release kinetics and loading for each therapeutic agent in an infected implant environment. Antibiotics contained in top layers can be tuned to provide a rapid release at early times sufficient to eliminate infection, followed by sustained release for several weeks, and the underlying BMP-2 component enables a long-term sustained release of BMP-2, which induced more significant and mechanically competent bone formation than a short-term burst release. The successful growth factor mediated osteointegration of the multilayered implants with the host tissue improved bone-implant interfacial strength 15-fold when compared with the uncoated one. These findings demonstrate the potential of this layered release strategy to introduce a durable next-generation implant solution, ultimately an important step forward to future large animal models toward the clinic. C1 [Min, Jouha; Choi, Ki Young; Dreaden, Erik C.; Braatz, Richard D.; Hammond, Paula T.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Min, Jouha; Choi, Ki Young; Dreaden, Erik C.; Hammond, Paula T.] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Padera, Robert F.; Spector, Myron] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Padera, Robert F.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Spector, Myron] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA. RP Hammond, PT (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA.; Hammond, PT (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM hammond@mit.edu RI CHOI, KI YOUNG/Q-7177-2016 FU National Institutes of Health, National Institute of Aging [5R01AG029601-03]; Koch Institute Core Grant from the NCI [P30-CA14051]; Army Research Office; Army Research Laboratories FX This work was partly supported by the National Institutes of Health, National Institute of Aging (5R01AG029601-03). We thank N. Shah, Ph.D. for consultation on in vivo experiment design, R. Bronson, Ph.D. for analysis of histological sections, and M. Bauer for special histology staining. We thank the MIT Koch Institute Swanson Biotechnology Center, which is supported by the Koch Institute Core Grant P30-CA14051 from the NCI, for the use of facilities, and specifically the Hope Babette Tang (1983) Histology Facility and The Animal Imaging & Preclinical Testing Core Facility. The authors wish to express their appreciation to the Institute for Soldier Nanotechnologies at MIT, supported by the Army Research Office and Army Research Laboratories, whose facilities and equipment were used to conduct the research reported in this paper. We thank the Robert Langer Laboratory for the use of liquid scintillation counter and Instron, as well as the Tyler Jacks Laboratory for the use of Nikon light microscope. We also acknowledge Pfizer. Inc. for rhBMP-2. NR 39 TC 9 Z9 10 U1 20 U2 43 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD APR PY 2016 VL 10 IS 4 BP 4441 EP 4450 DI 10.1021/acsnano.6b00087 PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA DK9IV UT WOS:000375245000062 PM 26923427 ER PT J AU Bauer, MS AF Bauer, Mark S. TI Hope, Faith, Love, and Treating Serious Mental Health Conditions SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 [Bauer, Mark S.] VA Boston Healthcare Syst, Boston, MA USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Bauer, MS (reprint author), VA Boston Healthcare Syst, Boston, MA USA.; Bauer, MS (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM mark.bauer@va.gov NR 1 TC 0 Z9 0 U1 3 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2016 VL 173 IS 4 BP 319 EP 320 DI 10.1176/appi.ajp.2016.15121604 PG 2 WC Psychiatry SC Psychiatry GA DK9ZH UT WOS:000375290400005 PM 27035530 ER PT J AU Greenwood, TA Light, GA Swerdlow, NR Calkins, ME Green, MF Gur, RE Gur, RC Lazzeroni, LC Nuechterlein, KH Olincy, A Radant, AD Seidman, LJ Siever, LJ Silverman, JM Stone, WS Sugar, CA Tsuang, DW Tsuang, MT Turetsky, BI Freedman, R Braff, DL AF Greenwood, Tiffany A. Light, Gregory A. Swerdlow, Neal R. Calkins, Monica E. Green, Michael F. Gur, Raquel E. Gur, Ruben C. Lazzeroni, Laura C. Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Sugar, Catherine A. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Freedman, Robert Braff, David L. TI Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SCHIZOTYPAL PERSONALITY-DISORDER; EVOKED RESPONSE SUPPRESSION; PREPULSE INHIBITION; P50 SUPPRESSION; ACOUSTIC STARTLE; CONSORTIUM; RELATIVES; GENETICS; RISK; ENDOPHENOTYPES AB Objective: The Consortium on the Genetics of Schizophrenia Family Study evaluated 12 primary and other supplementary neurocognitive and neurophysiological endophenotypes in schizophrenia probands and their families. Previous analyses of prepulse inhibition (PPI) and P50 gating measures in this sample revealed heritability estimates that were lower than expected based on earlier family studies. Here the authors investigated whether gating measures were more heritable in multiply affected families with a positive family history compared with families with only a single affected proband (singleton). Method: A total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype andclinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons. Results: Both PPI and P50 gating displayed substantially increased heritability in the 97 multiply affected families (47% and 36%, respectively) compared with estimates derived from the entire sample of 296 families (29% and 20%, respectively). However, no evidence for heritability was observed for either measure in the 96 singleton families. Schizophrenia probands derived from the multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those from singleton families. Conclusions: PPI and P50 gating measures demonstrate substantially increased heritability in schizophrenia families with a higher genetic vulnerability for illness, providing further support for the commonality of genes underlying both schizophrenia and gating measures. C1 [Greenwood, Tiffany A.] UCSanDiego, Ctr Behav Genom, Dept Psychiat, La Jolla, CA USA. [Greenwood, Tiffany A.] UCSanDiego, Inst Genom Med, La Jolla, CA USA. VA San Diego Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 22, San Diego, CA USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02215 USA. Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. James J Peters VA Med Ctr, New York, NY USA. RP Greenwood, TA (reprint author), UCSanDiego, Ctr Behav Genom, Dept Psychiat, La Jolla, CA USA.; Greenwood, TA (reprint author), UCSanDiego, Inst Genom Med, La Jolla, CA USA. EM tgreenwood@ucsd.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Greenwood, Tiffany/0000-0002-6080-6503 FU NIMH [R01-MH065571, R01-MH065588, R01-MH065562, R01-MH065707, R01-MH065554, R01-MH065578, R01-MH065558, R01 MH86135, K01-MH087889]; Amgen; Brain Plasticity; Genentech; Janssen Scientific Affairs FX Supported by NIMH grants R01-MH065571, R01-MH065588, R01-MH065562, R01-MH065707, R01-MH065554, R01-MH065578, R01-MH065558, R01 MH86135, and K01-MH087889.; Dr. Freedman has a patent through the VA on DNA sequences in CHRNA7. Dr. Green has been a consultant to AbbVie, Biogen, DSP, EnVivo/Forum, and Roche; he is on the scientific advisory board of Mnemosyne; and he has received research funds from Amgen. Dr. R.E. Gur has served as a consultant for Otsuka. Dr. Lazzeroni is an inventor on a patent application filed by Stanford University on genetic polymorphisms associated with depression. Dr. Light has served as a consultant for Astellas, Forum, and Neuroverse. Dr. Nuechterlein has received research support from Brain Plasticity, Genentech, and Janssen Scientific Affairs, and has served as a consultant for Brain Plasticity, Genentech, Janssen, and Otsuka. Dr. Swerdlow has served as a consultant for Genco Sciences. The other authors report no financial relationships with commercial interests. NR 60 TC 3 Z9 3 U1 3 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2016 VL 173 IS 4 BP 385 EP 391 DI 10.1176/appi.ajp.2015.15050605 PG 7 WC Psychiatry SC Psychiatry GA DK9ZH UT WOS:000375290400013 PM 26441157 ER PT J AU Xu, J Sun, HH Fletcher, CDM Hornick, JL Morgan, EA Freeman, GJ Hodi, FS Pinkus, GS Rodig, SJ AF Xu, Jie Sun, Heather H. Fletcher, Christopher D. M. Hornick, Jason L. Morgan, Elizabeth A. Freeman, Gordon J. Hodi, F. Stephen Pinkus, Geraldine S. Rodig, Scott J. TI Expression of Programmed Cell Death 1 Ligands (PD-L1 and PD-L2) in Histiocytic and Dendritic Cell Disorders SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE PD-L1; PD-L2; histiocytes; dendritic cells ID NECROTIZING LYMPHADENITIS; INTERFERON-GAMMA; LYMPHOMA; BLOCKADE; CANCER; SARCOIDOSIS; ACTIVATION; ANTIBODY; IMMUNITY; SAFETY AB Programmed cell death 1 ligands 1 and 2 (PD-L1 and PD-L2) are cell surface proteins expressed by activated antigen-presenting cells and by select malignancies that bind PD-1 on T cells to inhibit immune responses. Antibodies targeting PD-1 or PD-L1 elicit antitumor immunity in a subset of patients, and clinical response correlates with PD-1 ligand expression by malignant or immune cells within the tumor microenvironment. We examined the expression of PD-1 ligands on subsets of antigen-presenting cells and 87 histiocytic and dendritic cell disorders including those that are benign, borderline, and malignant. Within reactive lymphoid tissue, strong PD-L1 is detected on most macrophages, subsets of interdigitating dendritic cells, and plasmacytoid dendritic cells, but not on follicular dendritic cells or Langerhans cells. Macrophage/dendritic cell subsets do not express discernible PD-L2. Seven of 7 cases of sarcoidosis (100%), 6 of 6 cases of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) (100%), 2 of 11 cases of Rosai-Dorfman disease (18%), and 3 of 15 cases of Langerhans cell histiocytosis (20%) exhibited positivity for PD-L1. All cases of sarcoidosis were also positive for PD-L2. Seven of 14 histiocytic sarcomas (50%), 2 of 5 interdigitating dendritic cell sarcomas (40%), 10 of 20 follicular dendritic cell sarcomas (50%), and none of 9 blastic plasmacytoid dendritic cell neoplasms were positive for PD-L1. Eleven of 20 (55%) follicular dendritic cell sarcomas were also positive for PD-L2. PD-L1 and PD-L2 are useful new markers for identifying select histiocyte and dendritic cell disorders and reveal novel patient populations as rational candidates for immunotherapy. C1 [Xu, Jie; Sun, Heather H.; Fletcher, Christopher D. M.; Hornick, Jason L.; Morgan, Elizabeth A.; Pinkus, Geraldine S.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Amory 3rd Floor,75 Francis St, Boston, MA 02115 USA. [Freeman, Gordon J.; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hodi, F. Stephen; Rodig, Scott J.] Dana Farber Canc Inst, Dept Immunooncol, Boston, MA 02115 USA. RP Rodig, SJ (reprint author), Brigham & Womens Hosp, Dept Pathol, Amory 3rd Floor,75 Francis St, Boston, MA 02115 USA. EM srodig@partners.org FU Department of Pathology, BWH; Center for Immuno-Oncology of the Dana-Farber Cancer Institute; [P01AI056299]; [U54CA163125] FX Supported, in part by P01AI056299 and U54CA163125 (G.J.F.), the Department of Pathology, BWH, and the Center for Immuno-Oncology of the Dana-Farber Cancer Institute (S.J.R.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 26 TC 3 Z9 3 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2016 VL 40 IS 4 BP 443 EP 453 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA DK4PV UT WOS:000374901700004 PM 26752545 ER PT J AU Afrogheh, AH Jakobiec, FA Hammon, R Grossniklaus, HE Rocco, J Lindeman, NI Sadow, PM Faquin, WC AF Afrogheh, Amir H. Jakobiec, Frederick A. Hammon, Rebecca Grossniklaus, Hans E. Rocco, James Lindeman, Neal I. Sadow, Peter M. Faquin, William C. TI Evaluation for High-risk HPV in Squamous Cell Carcinomas and Precursor Lesions Arising in the Conjunctiva and Lacrimal Sac SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE human papilloma virus (HPV); high risk; conjunctiva; lacrimal sac; squamous cell carcinoma; PCR; p16; in situ hybridization (ISH); OSSNs ID HUMAN-PAPILLOMAVIRUS INFECTION; IN-SITU HYBRIDIZATION; POLYMERASE-CHAIN-REACTION; EPITHELIAL BASAL CELLS; OROPHARYNGEAL CANCER; INTRAEPITHELIAL NEOPLASIA; HIV-INFECTION; SINONASAL TRACT; STEM-CELLS; CORNEAL AB High-risk human papilloma virus (HR-HPV) is a well-established causative agent of oropharyngeal squamous cell carcinoma (SCC). In addition, HR-HPV has occasionally been reported to be present in dysplastic and malignant lesions of the conjunctiva and lacrimal sac, although its overall incidence and etiological role in periocular SCC are controversial. Sequential surgical samples of 52 combined cases of invasive SCC (I-SCC) and SCC in situ (SCCIS) from 2 periocular sites (conjunctiva and lacrimal sac) diagnosed over a 14-year period (2000 to 2014) were selected for evaluation, and relevant patient characteristics were documented. p16 immunohistochemistry was performed as a screening test. All p16-positive cases were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by polymerase chain reaction (PCR). Of 43 ocular surface squamous neoplasias (OSSNs), 30% (n=13; 8 SCCIS and 5 I-SCC cases) were positive for HR-HPV. HPV-positive OSSNs occurred in 8 men and 5 women with a mean age of 60 years (range, 39 to 94 y). HPV type-16 was detected in all conjunctival cases evaluated by PCR. All 5 conjunctival I-SCCs were nonkeratinizing (n=4) or partially keratinizing (n=1) and managed by simple excision. In contrast, HPV-negative conjunctival I-SCCs were predominantly keratinizing (11 keratinizing and 2 nonkeratinizing). Of 9 lacrimal sac I-SCCs (LSSCCs), 66.7% (n=6) were positive for HR-HPV by p16 and DNA ISH; HPV subtypes were HPV-16 (n=5) and HPV-58 (n=1). In addition, 2 p16-positive cases with negative DNA ISH results were HR-HPV positive (HPV-16 and HPV-33) when evaluated by PCR, suggesting that the rate of HR-HPV positivity among the LSSCCs may be as high as 89% (n=8). The combined group of HR-HPV-positive LSSCCs was seen in 4 men and 4 women with a mean age of 60 years (range, 34 to 71 y). Seven of the 8 HPV-positive LSSCCs (87.5%) had a nonkeratinizing or partially keratinizing histomorphology, whereas 1 case (12.5%) was predominantly keratinizing. The presence of HR-HPV in 30% of OSSNs and at least 66.7% of LSSCCs suggests the possibility of an etiologic role for HR-HPV at these sites. C1 [Afrogheh, Amir H.; Sadow, Peter M.; Faquin, William C.] Massachusetts Gen Hosp, Pathol Serv, WRN219,55 Fruit St, Boston, MA 02114 USA. [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Hammon, Rebecca; Sadow, Peter M.; Faquin, William C.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Afrogheh, Amir H.; Jakobiec, Frederick A.; Hammon, Rebecca; Lindeman, Neal I.; Sadow, Peter M.; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. [Grossniklaus, Hans E.] Emory Univ, Dept Ophthalmol, LF Montgomery Lab Ophthalm Pathol, Atlanta, GA 30322 USA. [Rocco, James] Ohio State Wexner Med Ctr, Div Head & Neck Oncol Surg, Columbus, OH USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Pathol Serv, WRN219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@mgh.harvard.edu NR 85 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2016 VL 40 IS 4 BP 519 EP 528 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA DK4PV UT WOS:000374901700013 PM 26735858 ER PT J AU Agoston, AT Strauss, AC Dulai, PS Hagen, CE Muzikansky, A Fudman, DI Abrams, JA Forcione, DG Jajoo, K Saltzman, JR Odze, RD Lauwers, GY Gordon, SR Lightdale, CJ Rothstein, RI Srivastava, A AF Agoston, Agoston T. Strauss, Adam C. Dulai, Parambir S. Hagen, Catherine E. Muzikansky, Alona Fudman, David I. Abrams, Julian A. Forcione, David G. Jajoo, Kunal Saltzman, John R. Odze, Robert D. Lauwers, Gregory Y. Gordon, Stuart R. Lightdale, Charles J. Rothstein, Richard I. Srivastava, Amitabh TI Predictors Of Treatment Failure After Radiofrequency Ablation For Intramucosal Adenocarcinoma in Barrett Esophagus A Multi-institutional Retrospective Cohort Study SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE radiofrequency ablation; endoscopic mucosal resection; intramucosal adenocarcinoma; Barrett esophagus ID ENDOSCOPIC MUCOSAL RESECTION; HIGH-GRADE DYSPLASIA; ERADICATION; OUTCOMES; NEOPLASIA; CANCER; EXPERIENCE; REGISTRY; THERAPY; SAFETY AB Radiofrequency ablation (RFA), with or without endoscopic mucosal resection (EMR), is a safe, effective, and durable treatment option for Barrett esophagus (BE)-associated dysplasia (DYS), but few studies have identified predictors of treatment failure in BE-associated intramucosal adenocarcinoma (IMC). The aim of this study was to determine the rate of IMC eradication when using RFA +/- EMR and to identify clinical and pathologic predictors of treatment failure. A retrospective review of medical records and a central review of index histologic parameters were performed for 78 patients who underwent RFA +/- EMR as the primary treatment for biopsy-proven IMC at 4 academic tertiary medical centers. Complete eradication (CE) (absence of IMC/DYS on first follow-up endoscopy) was achieved in 86% of patients, and durable eradication (DE) (CE with no recurrence of IMC/DYS until last follow-up) was achieved in 78% of patients, with significant variation between the 4 study sites (P=0.03 and 0.09 by analysis of variance for DE and CE, respectively). Use of EMR before RFA significantly reduced the risk for treatment failure for IMC/DYS (hazard ratio, 0.15; 95% confidence interval, 0.05-0.48; P=0.001), whereas IMC involving >= 50% of the columnar metaplastic area on index examination significantly increased the risk for treatment failure (hazard ratio, 4.24; 95% confidence interval, 1.53-11.7; P=0.005). Endoscopic and pathologic factors associated with treatment failure in BE-associated IMC treated with RFA +/- EMR may help identify the subset of IMC patients for whom a more aggressive initial approach may be justified. C1 [Agoston, Agoston T.; Odze, Robert D.; Srivastava, Amitabh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Jajoo, Kunal; Saltzman, John R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Strauss, Adam C.; Dulai, Parambir S.; Gordon, Stuart R.; Rothstein, Richard I.] Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. [Fudman, David I.; Abrams, Julian A.; Lightdale, Charles J.] Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY USA. [Hagen, Catherine E.; Forcione, David G.; Lauwers, Gregory Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Muzikansky, Alona] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. RP Srivastava, A (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM asrivastava@partners.org FU Barrx/Covidien; C2 Therapeutics/Covidien FX Dr Rothstein and Dr Abrams have received research support previously from Barrx/Covidien and C2 Therapeutics/Covidien, respectively. None of the other authors have significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 27 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 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2016 VL 40 IS 4 BP 554 EP 562 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA DK4PV UT WOS:000374901700017 PM 26645729 ER PT J AU Bennett, JA Lamb, C Young, RH AF Bennett, Jennifer A. Lamb, Colleen Young, Robert H. TI Apoplectic Leiomyomas A Morphologic Analysis of 100 Cases Highlighting Unusual Features SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE leiomyoma; apoplectic change; smooth muscle tumor; progestin therapy; oral contraceptives ID UTERINE LEIOMYOMAS; PROGESTIN THERAPY; UTERUS AB Leiomyomas with apoplectic change related to progestational effect have not received much attention in the literature and in our experience frequently cause diagnostic difficulty. We reviewed 100 apoplectic leiomyomas to characterize their broad histologic spectrum. The tumors occurred over a wide age range (mean, 41 y), and although 2 patients were pregnant, in the vast majority the apoplectic changes were likely due to progestins administered to help control symptoms related to the leiomyomas. Leiomyomas were multiple in 77% of patients, averaged 6 cm, and frequently showed gross features of hemorrhage, necrosis, cyst formation, softening, or color different than the usual banal leiomyoma. Microscopic examination typically revealed multiple stellate to ovoid zones with a hypercellular periphery and central hemorrhage, necrosis, or hyalinization. The hypercellular areas were often dominated by cells with eosinophilic cytoplasm, pyknotic nuclei, and increased mitoses (up to 14/10 high-power fields), but most tumors showed no appreciable cytologic atypia in these regions. Edema was noted in 95%, a hyalinized and/or myxoid matrix in 92%, and cyst formation in 42%. Because of these unusual features, difficulty often arose in determining whether the tumors were benign, malignant, or of uncertain malignant potential. Recognition of their wide morphologic spectrum will enable classification in the benign category and avoid undue patient anxiety and potentially unnecessary aggressive management. C1 [Bennett, Jennifer A.; Lamb, Colleen; Young, Robert H.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Bennett, Jennifer A.; Lamb, Colleen; Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Bennett, Jennifer A.] Lahey Hosp & Med Ctr, Dept Pathol, Burlington, MA USA. [Lamb, Colleen] William Beaumont Hosp, Royal Oak, MI 48072 USA. RP Bennett, JA (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA.; Bennett, JA (reprint author), Lahey Hosp & Med Ctr, Dept Pathol, Burlington, MA USA. EM jennifer.a.bennett@lahey.org NR 15 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2016 VL 40 IS 4 BP 563 EP 568 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA DK4PV UT WOS:000374901700018 PM 26685083 ER PT J AU Papathomas, TG Pucci, E Giordano, TJ Lu, H Duregon, E Volante, M Papotti, M Lloyd, RV Tischler, AS van Nederveen, FH Nose, V Erickson, L Mete, O Asa, SL Turchini, J Gill, AJ Matias-Guiu, X Skordilis, K Stephenson, TJ Tissier, F Feelders, RA Smid, M Nigg, A Korpershoek, E van der Spek, PJ Dinjens, WNM Stubbs, AP de Krijger, RR AF Papathomas, Thomas G. Pucci, Eugenio Giordano, Thomas J. Lu, Hao Duregon, Eleonora Volante, Marco Papotti, Mauro Lloyd, Ricardo V. Tischler, Arthur S. van Nederveen, Francien H. Nose, Vania Erickson, Lori Mete, Ozgur Asa, Sylvia L. Turchini, John Gill, Anthony J. Matias-Guiu, Xavier Skordilis, Kassiani Stephenson, Timothy J. Tissier, Frederique Feelders, Richard A. Smid, Marcel Nigg, Alex Korpershoek, Esther van der Spek, Peter J. Dinjens, Winand N. M. Stubbs, Andrew P. de Krijger, Ronald R. TI An International Ki67 Reproducibility Study in Adrenal Cortical Carcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Ki67 labeling index; proliferation; adrenal cortical carcinoma; interobserver variation; digital pathology ID QUANTITATIVE IMAGE-ANALYSIS; ADRENOCORTICAL CARCINOMA; NEUROENDOCRINE TUMORS; BREAST-CANCER; LABELING INDEX; PROLIFERATIVE INDEX; VISUAL ASSESSMENT; LIVER METASTASES; PROGNOSTIC VALUE; KI-67 AB Despite the established role of Ki67 labeling index in prognostic stratification of adrenocortical carcinomas and its recent integration into treatment flow charts, the reproducibility of the assessment method has not been determined. The aim of this study was to investigate interobserver variability among endocrine pathologists using a web-based virtual microscopy approach. Ki67-stained slides of 76 adrenocortical carcinomas were analyzed independently by 14 observers, each according to their method of preference including eyeballing, formal manual counting, and digital image analysis. The interobserver variation was statistically significant (P<0.001) in the absence of any correlation between the various methods. Subsequently, 61 static images were distributed among 15 observers who were instructed to follow a category-based scoring approach. Low levels of interobserver (F=6.99; F-crit=1.70; P<0.001) as well as intraobserver concordance (n=11; Cohen k ranging from -0.057 to 0.361) were detected. To improve harmonization of Ki67 analysis, we tested the utility of an open-source Galaxy virtual machine application, namely Automated Selection of Hotspots, in 61 virtual slides. The software-provided Ki67 values were validated by digital image analysis in identical images, displaying a strong correlation of 0.96 (P<0.0001) and dividing the cases into 3 classes (cutoffs of 0%-15%-30% and/or 0%-10%-20%) with significantly different overall survivals (P<0.05). We conclude that current practices in Ki67 scoring assessment vary greatly, and interobserver variation sets particular limitations to its clinical utility, especially around clinically relevant cutoff values. Novel digital microscopy-enabled methods could provide critical aid in reducing variation, increasing reproducibility, and improving reliability in the clinical setting. C1 [Papathomas, Thomas G.; Pucci, Eugenio; Nigg, Alex; Korpershoek, Esther; Dinjens, Winand N. M.; de Krijger, Ronald R.] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands. [Lu, Hao; van der Spek, Peter J.; Stubbs, Andrew P.] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Bioinformat, Rotterdam, Netherlands. [Smid, Marcel] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Med Oncol, Rotterdam, Netherlands. [Feelders, Richard A.] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Internal Med, Div Endocrinol, Rotterdam, Netherlands. [van Nederveen, Francien H.] PAL Dordrecht, Pathol Lab, Dordrecht, England. [de Krijger, Ronald R.] Reinier de Graaf Hosp, Dept Pathol, Delft, Netherlands. [de Krijger, Ronald R.] Univ Med Ctr Utrecht, Princess Maxima Ctr Pediat Oncol, Dept Pathol, Utrecht, Netherlands. [Papathomas, Thomas G.] Kings Coll London, Dept Histopathol, London WC2R 2LS, England. [Skordilis, Kassiani] Univ Hosp Birmingham, Dept Pathol, Birmingham, W Midlands, England. [Stephenson, Timothy J.] Royal Hallamshire Hosp, Dept Histopathol, Glossop Rd, Sheffield S10 2JF, S Yorkshire, England. [Pucci, Eugenio] Univ Roma La Sapienza, St Andrea Hosp, Pathol Unit, Dept Clin & Mol Med, Piazzale Aldo Moro 5, I-00185 Rome, Italy. [Duregon, Eleonora; Volante, Marco; Papotti, Mauro] Univ Turin, San Luigi Hosp, Dept Oncol, Orbassano, Italy. [Giordano, Thomas J.] Univ Michigan, Univ Michigan Hlth Syst, Ctr Comprehens Canc, Dept Pathol,Dept Internal Med, Ann Arbor, MI 48109 USA. [Lloyd, Ricardo V.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA. [Tischler, Arthur S.] Tufts Univ, Sch Med, Tufts Med Ctr, Dept Pathol & Lab Med, Medford, MA USA. [Nose, Vania] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Erickson, Lori] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Mete, Ozgur; Asa, Sylvia L.] Univ Toronto, Univ Hlth Network, Dept Pathol, Toronto, ON, Canada. [Turchini, John; Gill, Anthony J.] Royal N Shore Hosp, Dept Anat Pathol, Sydney, NSW, Australia. [Turchini, John; Gill, Anthony J.] Univ Sydney, Sydney, NSW 2006, Australia. [Matias-Guiu, Xavier] Univ Lleida, IRBLLEIDA, Hosp Univ Arnau Vilanova, Dept Pathol & Mol Genet & Res Lab, Lleida, Spain. [Tissier, Frederique] Paris Descartes Univ, Sorbonne Paris Cite, Inst Cochin, INSERM U1016 CNRS UMR8104, Paris, France. [Tissier, Frederique] Univ Paris 06, Sorbonne Univ, Pitie Salpetriere Hosp, AP HP,Dept Pathol, Paris, France. RP Papathomas, TG (reprint author), Kings Coll Hosp London, Dept Histopathol, Denmark Hill, London SE5 9RS, England. EM t.papathomas@erasmusmc.nl RI matias-guiu, xavier/C-3039-2009 OI matias-guiu, xavier/0000-0002-7201-6605 FU ENS@T-Cancer [259735]; AIRC, Milan [IG/14820/2013] FX Supported by the Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 259735 (ENS@T-Cancer). Further support was partially provided by grants from AIRC, Milan no. IG/14820/2013 (to M.P.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 36 TC 3 Z9 3 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2016 VL 40 IS 4 BP 569 EP 576 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA DK4PV UT WOS:000374901700019 PM 26685085 ER PT J AU Loehrer, AP Hawkins, AT Auchincloss, HG Song, ZR Hutter, MM Patel, VI AF Loehrer, Andrew P. Hawkins, Alexander T. Auchincloss, Hugh G. Song, Zirui Hutter, Matthew M. Patel, Virendra I. TI Impact of Expanded Insurance Coverage on Racial Disparities in Vascular Disease: Insights From Massachusetts SO ANNALS OF SURGERY LA English DT Article DE access to care; health care disparities; health insurance coverage; health policy; peripheral artery disease ID DIFFERENCE-IN-DIFFERENCES; HEALTH-CARE REFORM; LOWER-EXTREMITY AMPUTATION; DIFFERENCES MODELS; HISPANIC PATIENTS; UNITED-STATES; OUTCOMES; SURGERY; MORTALITY; EXPANSION AB Objective:To evaluate the impact of health insurance expansion on racial disparities in severity of peripheral arterial disease.Background:Lack of insurance and non-white race are associated with increased severity, increased amputation rates, and decreased revascularization rates in patients with peripheral artery disease (PAD). Little is known about how expanded insurance coverage affects disparities in presentation with and management of PAD. The 2006 Massachusetts health reform expanded coverage to 98% of residents and provided the framework for the Affordable Care Act.Methods:We conducted a retrospective cohort study of nonelderly, white and non-white patients admitted with PAD in Massachusetts (MA) and 4 control states. Risk-adjusted difference-in-differences models were used to evaluate changes in probability of presenting with severe disease. Multivariable linear regression models were used to evaluate disparities in disease severity before and after the 2006 health insurance expansion.Results:Before the 2006 MA insurance expansion, non-white patients in both MA and control states had a 12 to 13 percentage-point higher probability of presenting with severe disease (P < 0.001) than white patients. After the expansion, measured disparities in disease severity by patient race were no longer statistically significant in Massachusetts (+3.0 percentage-point difference, P = 0.385) whereas disparities persisted in control states (+10.0 percentage-point difference, P < 0.001). Overall, non-white patients in MA had an 11.2 percentage-point decreased probability of severe PAD (P = 0.042) relative to concurrent trends in control states.Conclusions:The 2006 Massachusetts insurance expansion was associated with a decreased probability of patients presenting with severe PAD and resolution of measured racial disparities in severe PAD in MA. C1 [Loehrer, Andrew P.; Hawkins, Alexander T.; Auchincloss, Hugh G.; Hutter, Matthew M.; Patel, Virendra I.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Song, Zirui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Song, Zirui] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Loehrer, AP (reprint author), Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, 165 Cambridge St,Suite 403, Boston, MA 02114 USA. EM aloehrer@partners.org FU Department of Surgery, Massachusetts General Hospital, Boston, MA; National Institute on Aging [F30-AG039175] FX Supported by Department of Surgery, Massachusetts General Hospital, Boston, MA. This work was also supported by a grant from the National Institute on Aging (F30-AG039175 to Z.S.). The authors declare no conflicts of interest. NR 44 TC 2 Z9 2 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD APR PY 2016 VL 263 IS 4 BP 705 EP 711 DI 10.1097/SLA.0000000000001310 PG 7 WC Surgery SC Surgery GA DK2YZ UT WOS:000374782700020 PM 26587850 ER PT J AU Winter, JM Jiang, W Basturk, O Mino-Kenudson, M Fong, ZV Tan, WP Lavu, H Vollmer, CM Furth, EE Haviland, D Klimstra, DS Jarnagin, WR Lillemoe, KD Yeo, CJ Fernandez-Del Castillo, C Allen, PJ AF Winter, Jordan M. Jiang, Wei Basturk, Olca Mino-Kenudson, Mari Fong, Zhi Ven Tan, Wei Phin Lavu, Harish Vollmer, Charles M. Furth, Emma E. Haviland, Dana Klimstra, David S. Jarnagin, William R. Lillemoe, Keith D. Yeo, Charles J. Fernandez-Del Castillo, Carlos Allen, Peter J. TI Recurrence and Survival After Resection of Small Intraductal Papillary Mucinous Neoplasm-associated Carcinomas (<= 20-mm Invasive Component): A Multi-institutional Analysis SO ANNALS OF SURGERY LA English DT Article DE IPMN; pancreatic adenocarcinoma; pancreatic cyst; recurrence; small IPMN-associates cancer ID HIGH-RISK INDIVIDUALS; PEUTZ-JEGHERS GENE; CELL LUNG-CANCER; PANCREATIC-CANCER; 1423 PANCREATICODUODENECTOMIES; TUMOR SIZE; ADENOCARCINOMA; EXPERIENCE; MUTATIONS; PROGNOSIS AB Background:Early invasive carcinoma may be encountered in association with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The natural history of these early invasive lesions is unknown.Methods:Pancreatic surgical databases from 4 high-volume centers were queried for IPMNs, with invasive components measuring 20mm or less. All cases were reviewed by GI gastrointestinal pathologists, and pathologic features were analyzed to identify predictors of recurrence and survival.Results:A total of 70 small IPMN-associated invasive carcinomas (20-mm invasion) were identified, comprising 25% of resected IPMN-associated carcinomas (n = 280). Most of these small invasive cancers were multifocal (66%), less than 10mm in size (73%), and arose in the setting of a main duct IPMN (96%). The most common adenocarcinoma subtypes were tubular (57%) and colloid (29%). Lymph node metastases were present in 19% of cases and 23% were T3 lesions. The overall recurrence rate was 24% (n = 17), and the median time to recurrence was 16 months (range: 4-132 months). Median and 5-year survival rates were 99 months and 59%. Recurrence patterns of invasive disease were local in 35%, distant in 47%, and both in 18%. Lymphatic spread and T3 stage were predictive of recurrence (univariate, P = 0.006), whereas tubular carcinoma type was the most predictive of poor overall survival (multivariate hazard ratio = 3.7, P = 0.04).Conclusions:This study represents the largest multi-institutional experience of resected small IPMN-associated carcinoma. Although these malignancies may frequently be cured with resection, recurrence risk is significant. Lymphatic spread, increased T stage, and tubular type carcinoma were associated with the poorest outcome. C1 [Winter, Jordan M.; Tan, Wei Phin; Lavu, Harish; Yeo, Charles J.] Thomas Jefferson Univ, Dept Surg, 1025 Walnut St,605 Coll Bldg, Philadelphia, PA 19107 USA. [Winter, Jordan M.; Tan, Wei Phin; Lavu, Harish; Yeo, Charles J.] Thomas Jefferson Univ, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA. [Jiang, Wei] Thomas Jefferson Univ, Dept Pathol, Philadelphia, PA 19107 USA. [Basturk, Olca; Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fong, Zhi Ven; Lillemoe, Keith D.; Fernandez-Del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Vollmer, Charles M.] Hosp Univ Penn, Dept Surg, 3400 Spruce St, Philadelphia, PA 19104 USA. [Furth, Emma E.] Hosp Univ Penn, Dept Pathol, 3400 Spruce St, Philadelphia, PA 19104 USA. [Haviland, Dana; Jarnagin, William R.; Allen, Peter J.] Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA. RP Winter, JM (reprint author), Thomas Jefferson Univ, Dept Surg, 1025 Walnut St,605 Coll Bldg, Philadelphia, PA 19107 USA. EM Jordan.winter@jefferson.edu FU NCI NIH HHS [P30 CA008748] NR 35 TC 8 Z9 8 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD APR PY 2016 VL 263 IS 4 BP 793 EP 801 DI 10.1097/SLA.0000000000001319 PG 9 WC Surgery SC Surgery GA DK2YZ UT WOS:000374782700031 PM 26135696 ER PT J AU Osseiran, S Evans, CL AF Osseiran, S. Evans, C. L. TI Sweating the small stuff SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Editorial Material ID STOKES-RAMAN SCATTERING C1 [Osseiran, S.; Evans, C. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 149 13th St, Charlestown, MA 02129 USA. [Osseiran, S.] Harvard Mit Div Hlth Sci & Technol, 77 Massachusetts Ave,E25-519, Cambridge, MA 02139 USA. RP Evans, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 149 13th St, Charlestown, MA 02129 USA. EM Evans.Conor@mgh.harvard.edu NR 7 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD APR PY 2016 VL 174 IS 4 BP 714 EP 715 DI 10.1111/bjd.14504 PG 2 WC Dermatology SC Dermatology GA DL0OA UT WOS:000375331100031 PM 27115582 ER PT J AU Sullivan, RJ AF Sullivan, R. J. TI Serum lactate dehydrogenase is a more useful biomarker of prognosis than serum S100B in patients with BRAF-mutant melanoma SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Editorial Material ID SURVIVAL C1 [Sullivan, R. J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, 55 Fruit St, Boston, MA 02114 USA. RP Sullivan, RJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, 55 Fruit St, Boston, MA 02114 USA. EM rsullivan7@mgh.harvard.edu NR 9 TC 0 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD APR PY 2016 VL 174 IS 4 BP 716 EP 717 DI 10.1111/bjd.14503 PG 2 WC Dermatology SC Dermatology GA DL0OA UT WOS:000375331100033 PM 27115584 ER PT J AU Niehues, H van Vlijmen-Willems, IMJJ Bergboer, JGM Kersten, FFJ Narita, M Hendriks, WJAJ van den Bogaard, EH Zeeuwen, PLJM Schalkwijk, J AF Niehues, H. van Vlijmen-Willems, I. M. J. J. Bergboer, J. G. M. Kersten, F. F. J. Narita, M. Hendriks, W. J. A. J. van den Bogaard, E. H. Zeeuwen, P. L. J. M. Schalkwijk, J. TI Late cornified envelope (LCE) proteins: distinct expression patterns of LCE2 and LCE3 members suggest nonredundant roles in human epidermis and other epithelia SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID ATOPIC-DERMATITIS PATIENTS; STRATUM-CORNEUM; SKIN BARRIER; TERMINAL DIFFERENTIATION; PSORIASIS; FILAGGRIN; GENES; KERATINOCYTES; INDUCTION; PHENOTYPES AB Background Deletion of the late cornified envelope (LCE) proteins LCE3B and LCE3C is a strong and widely replicated psoriasis risk factor. It is amenable to biological analysis because it precludes the expression of two epidermis-specific proteins, rather than being a single-nucleotide polymorphism of uncertain significance. The biology of the 18-member LCE family of highly homologous proteins has remained largely unexplored so far. Objectives To analyse LCE3 expression at the protein level in human epithelia, as a starting point for functional analyses of these proteins in health and disease. Methods We generated the first pan-LCE3 monoclonal antibody and provide a detailed analysis of its specificity towards individual LCE members. LCE2 and LCE3 expression in human tissues and in reconstructed human skin models was studied using immunohistochemical analyses and quantitative polymerase chain reaction. Results Our study reveals that LCE2 and LCE3 proteins are differentially expressed in human epidermis, and colocalize only in the upper stratum granulosum layer. Using an in vitro reconstructed human skin model that mimics epidermal morphogenesis, we found that LCE3 proteins are expressed at an early time point during epidermal differentiation in the suprabasal layers, while LCE2 proteins are found only in the uppermost granular layer and stratum corneum. Conclusions Based on the localization of LCE2 and LCE3 in human epidermis we conclude that members of the LCE protein family are likely to have distinct functions in epidermal biology. This finding may contribute to understanding why LCE3B/C deletion increases psoriasis risk. C1 [Niehues, H.; van Vlijmen-Willems, I. M. J. J.; Kersten, F. F. J.; van den Bogaard, E. H.; Zeeuwen, P. L. J. M.; Schalkwijk, J.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Dermatol, POB 9101, NL-6500 HB Nijmegen, Netherlands. [Hendriks, W. J. A. J.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Cell Biol, POB 9101, NL-6500 HB Nijmegen, Netherlands. [Bergboer, J. G. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Narita, M.] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Cambridge, England. RP Schalkwijk, J (reprint author), Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Dermatol, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM joost.schalkwijk@radboudumc.nl RI Hendriks, Wiljan/A-5214-2013; Niehues, Hanna/P-5071-2015 OI Hendriks, Wiljan/0000-0001-9481-8281; Niehues, Hanna/0000-0002-6954-6955 FU ZonMw TOP grant [91211052]; National Psoriasis Foundation U.S.A. FX This study was funded by ZonMw TOP grant 91211052, and by a personal grant to P.L.J.M.Z. from the National Psoriasis Foundation U.S.A. NR 34 TC 1 Z9 1 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD APR PY 2016 VL 174 IS 4 BP 795 EP 802 DI 10.1111/bjd.14284 PG 8 WC Dermatology SC Dermatology GA DL0OA UT WOS:000375331100047 PM 26556599 ER PT J AU Nishino, M Chambers, ES Chong, CR Ramaiya, NH Gray, SW Marcoux, JP Hatabu, H Janne, PA Hodi, FS Awad, MM AF Nishino, Mizuki Chambers, Emily S. Chong, Curtis R. Ramaiya, Nikhil H. Gray, Stacy W. Marcoux, J. Paul Hatabu, Hiroto Janne, Pasi A. Hodi, F. Stephen Awad, Mark M. TI Anti-PD-1 Inhibitor-Related Pneumonitis in Non-Small Cell Lung Cancer SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID LONG-TERM SAFETY; ADVANCED MELANOMA; NIVOLUMAB; SURVIVAL; PEMBROLIZUMAB; IPILIMUMAB; TRIAL; IMMUNOTHERAPY; DOCETAXEL; ANTIBODY AB The recent approval of two PD-1 inhibitors for the treatment of non-small cell lung cancer (NSCLC) has rapidly led to the widespread use of these agents in oncology practices. Pneumonitis has been recognized as a potentially life-threatening adverse event amongNSCLCpatients treated with PD-1 inhibitors; however, the detailed clinical and radiographic manifestations of this entity remain to be described. We report on two cases of anti-PD-1 pneumonitis in advanced NSCLC patients treated with nivolumab after its FDA approval. Both patients presented with groundglass and reticular opacities and consolidations in a peripheral distribution on CT, demonstrating a radiographic pattern of cryptogenic organizing pneumonia. Consolidations were extensive and rapidly developed within 8 weeks of therapy in both cases. Both patients were treated with corticosteroids with subsequent improvement of respiratory symptoms and radiographic findings. One patient experienced recurrent pneumonitis after completing corticosteroid taper, or a "pneumonitis flare," in the absence of nivolumab retreatment, with subsequent improvement upon corticosteroid readministration. With the increasing use of immune checkpoint inhibitors in a growing number of tumor types, awareness of the radiographic and clinical manifestations of PD-1 inhibitor-related pneumonitis will be critical for the prompt diagnosis and management of this potentially serious adverse event. (C) 2016 AACR. C1 [Nishino, Mizuki; Ramaiya, Nikhil H.; Hatabu, Hiroto] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Nishino, Mizuki; Ramaiya, Nikhil H.; Hatabu, Hiroto] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. [Chambers, Emily S.; Chong, Curtis R.; Gray, Stacy W.; Marcoux, J. Paul; Janne, Pasi A.; Hodi, F. Stephen; Awad, Mark M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chambers, Emily S.; Chong, Curtis R.; Gray, Stacy W.; Marcoux, J. Paul; Janne, Pasi A.; Hodi, F. Stephen; Awad, Mark M.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Chambers, Emily S.; Chong, Curtis R.; Gray, Stacy W.; Marcoux, J. Paul; Janne, Pasi A.; Hodi, F. Stephen; Awad, Mark M.] Brigham & Womens Hosp, 450 Brookline Ave, Boston, MA 02215 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.; Nishino, M (reprint author), Brigham & Womens Hosp, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@dfci.harvard.edu FU NCI [1K23CA157631] FX M. Nishino, was supported by 1K23CA157631 (NCI). NR 16 TC 15 Z9 15 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD APR PY 2016 VL 4 IS 4 BP 289 EP 293 DI 10.1158/2326-6066.CIR-15-0267 PG 5 WC Oncology; Immunology SC Oncology; Immunology GA DL1RP UT WOS:000375410000003 PM 26865455 ER PT J AU Abels, ER Breakefield, XO AF Abels, Erik R. Breakefield, Xandra O. TI Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Editorial Material DE Extracellular vesicles; Exosomes; Microvesicles; Biogenesis; RNA; Cargo selection ID MULTIVESICULAR BODY FORMATION; DIACYLGLYCEROL-KINASE-ALPHA; CELL-DERIVED EXOSOMES; RED-BLOOD-CELLS; MEMBRANE-VESICLES; RECIPIENT CELLS; INTERCELLULAR COMMUNICATION; MICROVESICLES CARRY; PROTEOMIC ANALYSIS; APOPTOTIC BODIES AB Extracellular vesicles are a heterogeneous group of membrane-limited vesicles loaded with various proteins, lipids, and nucleic acids. Release of extracellular vesicles from its cell of origin occurs either through the outward budding of the plasma membrane or through the inward budding of the endosomal membrane, resulting in the formation of multivesicular bodies, which release vesicles upon fusion with the plasma membrane. The release of vesicles can facilitate intercellular communication by contact with or by internalization of contents, either by fusion with the plasma membrane or by endocytosis into "recipient" cells. Although the interest in extracellular vesicle research is increasing, there are still no real standards in place to separate or classify the different types of vesicles. This review provides an introduction into this expanding and complex field of research focusing on the biogenesis, nucleic acid cargo loading, content, release, and uptake of extracellular vesicles. C1 [Abels, Erik R.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Abels, Erik R.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Abels, Erik R.; Breakefield, Xandra O.] Harvard Univ, Sch Med, NeuroDiscovery Ctr, Boston, MA 02114 USA. [Abels, Erik R.] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Neurooncol Res Grp, NL-1007 MB Amsterdam, Netherlands. RP Abels, ER (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA.; Abels, ER (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA.; Abels, ER (reprint author), Harvard Univ, Sch Med, NeuroDiscovery Ctr, Boston, MA 02114 USA.; Abels, ER (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Neurooncol Res Grp, NL-1007 MB Amsterdam, Netherlands. EM eabels@mgh.harvard.edu NR 134 TC 15 Z9 16 U1 8 U2 17 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 EI 1573-6830 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD APR PY 2016 VL 36 IS 3 SI SI BP 301 EP 312 DI 10.1007/s10571-016-0366-z PG 12 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA DL1HN UT WOS:000375383300001 PM 27053351 ER PT J AU Hall, J Prabhakar, S Balaj, L Lai, CP Cerione, RA Breakefield, XO AF Hall, Justin Prabhakar, Shilpa Balaj, Leonora Lai, Charles P. Cerione, Richard A. Breakefield, Xandra O. TI Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson's Disease, Glioma, and Schwannoma SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Review DE Exosomes; Extracellular vesicles; Parkinson's disease; Glioma; Schwannoma; Therapeutic protein delivery ID CELL-DERIVED MICROVESICLES; IN-VIVO; TUMOR-CELLS; CYTOSINE DEAMINASE; PANCREATIC-CANCER; OXIDATIVE STRESS; RECIPIENT CELLS; LEUKEMIA-CELLS; STROMAL CELLS; SUICIDE GENE AB Extracellular vesicles present an attractive delivery vehicle for therapeutic proteins. They intrinsically contain many proteins which can provide information to other cells. Advantages include reduced immune reactivity, especially if derived from the same host, stability in biologic fluids, and ability to target uptake. Those from mesenchymal stem cells appear to be intrinsically therapeutic, while those from cancer cells promote tumor progression. Therapeutic proteins can be loaded into vesicles by overexpression in the donor cell, with oligomerization and membrane sequences increasing their loading. Examples of protein delivery for therapeutic benefit in pre-clinical models include delivery of: catalase for Parkinson's disease to reduce oxidative stress and thus help neurons to survive; prodrug activating enzymes which can convert a prodrug which crosses the blood-brain barrier into a toxic chemotherapeutic drug for schwannomas and gliomas; and the apoptosis-inducing enzyme, caspase-1 under a Schwann cell specific promoter for schwannoma. This therapeutic delivery strategy is novel and being explored for a number of diseases. C1 [Hall, Justin; Cerione, Richard A.] Cornell Univ, Dept Chem, Ithaca, NY 14853 USA. [Hall, Justin; Cerione, Richard A.] Cornell Univ, Dept Chem Biol & Mol Med, Ithaca, NY 14853 USA. [Hall, Justin; Prabhakar, Shilpa; Balaj, Leonora; Lai, Charles P.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hall, Justin; Prabhakar, Shilpa; Balaj, Leonora; Lai, Charles P.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Hall, Justin; Prabhakar, Shilpa; Balaj, Leonora; Lai, Charles P.; Breakefield, Xandra O.] Harvard Univ, Sch Med, NeuroDiscovery Ctr, Boston, MA 02114 USA. [Lai, Charles P.] Natl Tsing Hua Univ, Inst Biomed Engn, Hsinchu 30013, Taiwan. [Breakefield, Xandra O.] Massachusetts Gen Hosp East, Mol Neurogenet Unit, 13th St,Bldg 149, Charlestown, MA 02129 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.; Breakefield, XO (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA.; Breakefield, XO (reprint author), Harvard Univ, Sch Med, NeuroDiscovery Ctr, Boston, MA 02114 USA. EM breakefield@hms.harvard.edu RI Lai, Charles/D-5442-2017 FU NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director [NCI U19 CA179563]; Voices Against Brain Cancer FX We thank Suzanne McDavitt for skilled editorial assistance and Dr. Bence Gyorgy for insights into packaging of different length mRNAs into EVs. This work was supported by the NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director, NCI U19 CA179563 (XOB) and Voices Against Brain Cancer (XOB & CPL). NR 81 TC 5 Z9 5 U1 13 U2 24 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 EI 1573-6830 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD APR PY 2016 VL 36 IS 3 SI SI BP 417 EP 427 DI 10.1007/s10571-015-0309-0 PG 11 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA DL1HN UT WOS:000375383300010 PM 27017608 ER PT J AU Loov, C Scherzer, CR Hyman, BT Breakefield, XO Ingelsson, M AF Loeoev, Camilla Scherzer, Clemens R. Hyman, Bradley T. Breakefield, Xandra O. Ingelsson, Martin TI alpha-Synuclein in Extracellular Vesicles: Functional Implications and Diagnostic Opportunities SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Review DE Extracellular vesicles; Exosomes; alpha-Synuclein ID NEURONAL CELL-DEATH; PARKINSONS-DISEASE; IN-VIVO; ACTIVATES MICROGLIA; BRAIN PATHOLOGY; ELEVATED LEVELS; OLIGOMERS; EXOSOMES; TRANSMISSION; BIOMARKERS AB Fibrillar inclusions of intraneuronal alpha-synuclein can be detected in certain brain areas from patients with Parkinson's disease (PD) and other disorders with Lewy body pathology. These insoluble protein aggregates do not themselves appear to have a prominent neurotoxic effect, whereas various alpha-synuclein oligomers appear harmful. Although it is incompletely known how the pre-fibrillar species may be pathogenic, they have been detected both within and on the outside of exosomes and other extracellular vesicles (EVs), suggesting that such structures may mediate toxic alpha-synuclein propagation between neurons. Vesicular transfer of alpha-synuclein may thereby contribute to the hierarchical spreading of pathology seen in the PD brain. Although the regulation of alpha-synuclein release via EVs is not understood, data suggest that it may involve other PD-related molecules, such as LRRK2 and ATP13A2. Moreover, new evidence indicates that CNS-derived EVs in plasma have the potential to serve as biomarkers for diagnostic purposes. In a recent study, levels of alpha-synuclein were found to be increased in L1CAM-positive vesicles isolated from plasma of PD patients compared to healthy controls, and follow-up studies will reveal whether alpha-synuclein in EVs could be developed as a future disease biomarker. Preferentially, toxic prefibrillar alpha-synuclein oligomers should then be targeted as a biomarker-as evidence suggests that they reflect the disease process more closely than total alpha-synuclein content. In such studies, it will be essential to adopt stringent EV isolation protocols in order to avoid contamination from the abundant pool of free plasma alpha-synuclein in different aggregational states. C1 [Loeoev, Camilla; Hyman, Bradley T.; Breakefield, Xandra O.; Ingelsson, Martin] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Loeoev, Camilla; Hyman, Bradley T.; Breakefield, Xandra O.; Ingelsson, Martin] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Loeoev, Camilla; Breakefield, Xandra O.; Ingelsson, Martin] Harvard Univ, Sch Med, Ctr NeuroDiscovery, Boston, MA USA. [Hyman, Bradley T.] Harvard Univ, Sch Med, Alzheimers Dis Res Ctr, Boston, MA USA. [Scherzer, Clemens R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Neurogen Lab, Cambridge, MA 02139 USA. [Scherzer, Clemens R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Parkinson Personalized Med Program, Cambridge, MA 02139 USA. [Ingelsson, Martin] Uppsala Univ, Dept Publ Hlth, Mol Geriatr, Rudbeck Lab, Uppsala, Sweden. RP Ingelsson, M (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.; Ingelsson, M (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.; Ingelsson, M (reprint author), Harvard Univ, Sch Med, Ctr NeuroDiscovery, Boston, MA USA.; Ingelsson, M (reprint author), Uppsala Univ, Dept Publ Hlth, Mol Geriatr, Rudbeck Lab, Uppsala, Sweden. EM martin.ingelsson@pubcare.uu.se FU Harvard NeuroDiscovery Center (HNDC); Parkinson's Disease Biomarkers Program (PDBP) of the NINDS [U01 NS082157]; Massachusetts Alzheimer's Disease Research Center (ADRC) Grant of the National Institute on Aging [P50 AG005134]; NIH [U01 NS082157, U01 NS082080]; U.S. Department of Defense [W81XWH-13-1-0115]; M.E.M.O. Hoffman Foundation FX We thank Drs. Leonora Balaj and Xuan Zhang for valuable advice and guidance with the experimental part. Biospecimens were provided by the Harvard Biomarkers Study. The Harvard Biomarkers Study is co-directed by Drs. Clemens R. Scherzer, Bradley T. Hyman, and Adrian Ivinson and supported by the Harvard NeuroDiscovery Center (HNDC), the Parkinson's Disease Biomarkers Program (PDBP) Grant U01 NS082157 of the NINDS (to C.R.S), a gift from Rick and Nancy Moskovitz (to A.J.I.) and the Massachusetts Alzheimer's Disease Research Center (ADRC) P50 AG005134 Grant of the National Institute on Aging (to B.T.H.). CRS' work is supported by NIH Grants U01 NS082157 and U01 NS082080, and U.S. Department of Defense Grant W81XWH-13-1-0115, as well as the M.E.M.O. Hoffman Foundation (C.R.S.). NR 71 TC 6 Z9 6 U1 3 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 EI 1573-6830 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD APR PY 2016 VL 36 IS 3 SI SI BP 437 EP 448 DI 10.1007/s10571-015-0317-0 PG 12 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA DL1HN UT WOS:000375383300012 PM 26993503 ER PT J AU Zhang, X Abels, ER Redzic, JS Margulis, J Finkbeiner, S Breakefield, XO AF Zhang, Xuan Abels, Erik R. Redzic, Jasmina S. Margulis, Julia Finkbeiner, Steve Breakefield, Xandra O. TI Potential Transfer of Polyglutamine and CAG-Repeat RNA in Extracellular Vesicles in Huntington's Disease: Background and Evaluation in Cell Culture SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Review DE Exosomes; Trinucleotide repeat; Neurodegeneration; Huntington's disease ID NEURONAL INTRANUCLEAR INCLUSIONS; ALZHEIMERS-DISEASE; MUTANT HUNTINGTIN; DROSOPHILA BRAIN; HD MUTATION; EXOSOMES; TRANSLATION; PROTEIN; MECHANISMS; TRANSMISSION AB In Huntington's disease (HD) the imperfect expanded CAG repeat in the first exon of the HTT gene leads to the generation of a polyglutamine (polyQ) protein, which has some neuronal toxicity, potentially mollified by formation of aggregates. Accumulated research, reviewed here, implicates both the polyQ protein and the expanded repeat RNA in causing toxicity leading to neurodegeneration in HD. Different theories have emerged as to how the neurodegeneration spreads throughout the brain, with one possibility being the transport of toxic protein and RNA in extracellular vesicles (EVs). Most cell types in the brain release EVs and these have been shown to contain neurodegenerative proteins in the case of prion protein and amyloid-beta peptide. In this study, we used a model culture system with an overexpression of HTT-exon 1 polyQ-GFP constructs in human 293T cells and found that the EVs did incorporate both the polyQ-GFP protein and expanded repeat RNA. Striatal mouse neural cells were able to take up these EVs with a consequent increase in the green fluorescent protein (GFP) and polyQ-GFP RNAs, but with no evidence of uptake of polyQ-GFP protein or any apparent toxicity, at least over a relatively short period of exposure. A differentiated striatal cell line expressing endogenous levels of Hdh mRNA containing the expanded repeat incorporated more of this mRNA into EVs as compared to similar cells expressing this mRNA with a normal repeat length. These findings support the potential of EVs to deliver toxic expanded trinucleotide repeat RNAs from one cell to another, but further work will be needed to evaluate potential EV and cell-type specificity of transfer and effects of long-term exposure. It seems likely that expanded HD-associated repeat RNA may appear in biofluids and may have use as biomarkers of disease state and response to therapy. C1 [Zhang, Xuan; Abels, Erik R.; Breakefield, Xandra O.] Massachusetts Gen Hosp East, Dept Neurol, Mol Neurogenet Unit, 13th St,Bldg 149, Charlestown, MA 02129 USA. [Zhang, Xuan; Abels, Erik R.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA USA. [Zhang, Xuan; Abels, Erik R.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Ctr NeuroDiscovery, Boston, MA USA. [Redzic, Jasmina S.] Univ Colorado, Dept Pharmaceut Sci, Denver Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA. [Margulis, Julia; Finkbeiner, Steve] Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA 94143 USA. [Margulis, Julia; Finkbeiner, Steve] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Margulis, Julia; Finkbeiner, Steve] Univ Calif San Francisco, Dept Physiol, Box 0444, San Francisco, CA USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp East, Dept Neurol, Mol Neurogenet Unit, 13th St,Bldg 149, Charlestown, MA 02129 USA.; Breakefield, XO (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA USA.; Breakefield, XO (reprint author), Harvard Univ, Sch Med, Ctr NeuroDiscovery, Boston, MA USA. EM xzhang23@mgh.harvard.edu; eabels@mgh.harvard.edu; jasmina.redzic@ucdenver.edu; julia.margulis@ucsf.edu; sfinkbeiner@gladstone.ucsf.edu; breakefield@hms.harvard.edu FU NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director; NCI [U19 CA179563]; NIH NRSA NIA postdoctoral training grant [2T32AG000222]; NIH [3R01 NS039074] FX We thank Ms. Suzanne McDavitt for skilled editorial assistance. Drs. Marian DiFiglia, Ellen Sapp, and Neal Aronin for insightful comments on HD pathophysiology. This work was supported by the NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director, NCI U19 CA179563 (XOB), and NIH NRSA NIA postdoctoral training grant, 2T32AG000222 (JSR). Additional support was from NIH 3R01 NS039074 (SF). Lentiviral vectors were produced by the MGH Vector Core supported by NIN/NINDS P30 NS045775 (XOB and Dr. Bakhos Tannous). NR 50 TC 1 Z9 1 U1 3 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 EI 1573-6830 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD APR PY 2016 VL 36 IS 3 SI SI BP 459 EP 470 DI 10.1007/s10571-016-0350-7 PG 12 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA DL1HN UT WOS:000375383300014 PM 26951563 ER PT J AU Figueroa, AL Takx, RAP MacNabb, MH Abdelbaky, A Lavender, ZR Kaplan, RS Truong, QA Lo, J Ghoshhajra, BB Grinspoon, SK Hoffmann, U Tawakol, A AF Figueroa, Amparo L. Takx, Richard A. P. MacNabb, Megan H. Abdelbaky, Amr Lavender, Zachary R. Kaplan, Rebecca S. Truong, Quynh A. Lo, Janet Ghoshhajra, Brian B. Grinspoon, Steven K. Hoffmann, Udo Tawakol, Ahmed TI Relationship Between Measures of Adiposity, Arterial Inflammation, and Subsequent Cardiovascular Events SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE adipose tissue; atherosclerosis; cardiovascular events; obesity; positron emission tomography ID ATHEROSCLEROTIC PLAQUE INFLAMMATION; BODY-MASS INDEX; POSITRON-EMISSION-TOMOGRAPHY; METABOLIC RISK-FACTORS; C-REACTIVE PROTEIN; CARDIOMETABOLIC RISK; SUBCUTANEOUS FAT; TISSUE VOLUMES; DISEASE; OBESITY AB Background The objective of this study was to evaluate how different measures of adiposity are related to both arterial inflammation and the risk of subsequent cardiovascular events. Methods and Results We included individuals who underwent F-18-fluorodeoxyglucose positron emission tomography/computed tomography imaging for oncological evaluation. Subcutaneous adipose tissue (SAT) volume, visceral adipose tissue (VAT) volume, and VAT/SAT ratio were determined. Additionally, body mass index, metabolic syndrome, and aortic F-18-fluorodeoxyglucose uptake (a measure of arterial inflammation) were determined. Subsequent development of cardiovascular disease (CVD) events was adjudicated. The analysis included 415 patients with a median age of 55 (P25-P75: 45-65) and a median body mass index of 26.4 (P25-P75: 23.4-30.9) kg/m(2). VAT and SAT volume were significantly higher in obese individuals. VAT volume (r=0.290; P<0.001) and VAT/SAT ratio (r=0.208; P<0.001) were positively correlated with arterial inflammation. Thirty-two subjects experienced a CVD event during a median follow-up of 4 years. Cox proportional hazard models showed that VAT volume and VAT/SAT ratio were associated with CVD events (hazard ratio [95% confidence interval]: 1.15 [1.06-1.25]; P<0.001; 3.60 [1.88-6.92]; P<0.001, respectively). Body mass index, metabolic syndrome, and SAT were not predictive of CVD events. Conclusions Measures of visceral fat are positively related to arterial inflammation and are independent predictors of subsequent CVD events. Individuals with higher measures of visceral fat as well as elevated arterial inflammation are at highest risk for subsequent CVD events. The findings suggest that arterial inflammation may explain some of the CVD risk associated with adiposity. C1 [Figueroa, Amparo L.; Takx, Richard A. P.; MacNabb, Megan H.; Abdelbaky, Amr; Lavender, Zachary R.; Kaplan, Rebecca S.; Ghoshhajra, Brian B.; Hoffmann, Udo; Tawakol, Ahmed] Massachusetts Gen Hosp, Dept Imaging, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Figueroa, Amparo L.; Takx, Richard A. P.; MacNabb, Megan H.; Abdelbaky, Amr; Lavender, Zachary R.; Kaplan, Rebecca S.; Ghoshhajra, Brian B.; Hoffmann, Udo; Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lo, Janet; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Takx, Richard A. P.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands. [Truong, Quynh A.] Weill Cornell Coll Med, Dept Radiol, New York, NY USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@partners.org FU Van Leersum Grant of the Royal Netherlands Academy of Arts and Sciences; Actelion; Genentech; Takeda; Theratechnologies; Gilead; Amgen FX Dr Takx is supported by Van Leersum Grant of the Royal Netherlands Academy of Arts and Sciences. Dr Tawakol is a consultant for Actelion, Amgen, AstraZeneca, and Takeda and received research grants from Actelion, Genentech, and Takeda. Dr Grinspoon is a consultant for and received research grants from Theratechnologies, Gilead, Amgen, and served as a consultant for NovoNordisk, BMS, Merck, Navidea, Aileron. All other authors have reported that they have no relationships relevant to the contents of this article to disclose. NR 41 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD APR PY 2016 VL 9 IS 4 AR e004043 DI 10.1161/CIRCIMAGING.115.004043 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DK3DG UT WOS:000374795700003 PM 27072302 ER PT J AU Rischpler, C Dirschinger, RJ Nekolla, SG Kossmann, H Nicolosi, S Hanus, F van Marwick, S Kunze, KP Meinicke, A Gotze, K Kastrati, A Langwieser, N Ibrahim, T Nahrendorf, M Schwaiger, M Laugwitz, KL AF Rischpler, Christoph Dirschinger, Ralf J. Nekolla, Stephan G. Kossmann, Hans Nicolosi, Stefania Hanus, Franziska van Marwick, Sandra Kunze, Karl P. Meinicke, Alexander Goetze, Katharina Kastrati, Adnan Langwieser, Nicolas Ibrahim, Tareq Nahrendorf, Matthias Schwaiger, Markus Laugwitz, Karl-Ludwig TI Prospective Evaluation of F-18-Fluorodeoxyglucose Uptake in Postischemic Myocardium by Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging as a Prognostic Marker of Functional Outcome SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE 18-fluorodeoxyglucose; inflammation; magnetic resonance imaging; monocytes; myocardial infarction; positron emission tomography ID MONOCYTE SUBSETS; HEART-FAILURE; GLUCOSE-METABOLISM; INFARCTION; INFLAMMATION; PET; ATHEROSCLEROSIS; MACROPHAGES; FDG; ACCUMULATION AB Background The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI F-18-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of F-18-FDG positron emission tomography/magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. Methods and Results We prospectively enrolled 49 patients with ST-segment-elevation myocardial infarction and performed F-18-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, Tc-99m-sestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of F-18-FDG-uptake and late gadolinium enhancement showed substantial overlap (=0.66), whereas quantitative analysis demonstrated that F-18-FDG extent exceeded late gadolinium enhancement extent (33.216.2% left ventricular myocardium versus 20.4 +/- 10.6% left ventricular myocardium, P<0.0001) and corresponded to the area at risk (r=0.87, P<0.0001). The peripheral blood count of CD14(high)/CD16(+) monocytes correlated with the infarction size and F-18-FDG signal extent (r=0.53, P<0.002 and r=0.42, P<0.02, respectively). F-18-FDG uptake in the infarcted myocardium was highest in areas with transmural scar, and the standardized uptake value(mean) was associated with left ventricular functional outcome independent of infarct size ( ejection fraction: P<0.04, end-diastolic volume: P<0.02, end-systolic volume: P<0.005). Conclusions In this study, the intensity of F-18-FDG uptake in the myocardium after acute myocardial infarction correlated inversely with functional outcome at 6 months. Thus, F-18-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury. C1 [Rischpler, Christoph; Nekolla, Stephan G.; Nicolosi, Stefania; van Marwick, Sandra; Kunze, Karl P.; Meinicke, Alexander; Schwaiger, Markus] Tech Univ Munich, Klinikum Rechts Isar, Nukl Med Klin & Poliklin, D-81675 Munich, Germany. [Dirschinger, Ralf J.; Kossmann, Hans; Hanus, Franziska; Langwieser, Nicolas; Ibrahim, Tareq; Laugwitz, Karl-Ludwig] Tech Univ Munich, Klinikum Rechts Isar, Med Klin & Poliklin 1, Ismaninger Str 22, D-81675 Munich, Germany. [Goetze, Katharina] Tech Univ Munich, Klinikum Rechts Isar, Med Klin & Poliklin 3, D-81675 Munich, Germany. [Kastrati, Adnan] Tech Univ Munich, Deutsch Herzzentrum, D-81675 Munich, Germany. [Rischpler, Christoph; Nekolla, Stephan G.; Kastrati, Adnan; Schwaiger, Markus; Laugwitz, Karl-Ludwig] DZKH Deutsch Zentrum Herz Kreislauf Forsch eV, Munich Heart Alliance, Partner Site, Munich, Germany. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Laugwitz, KL (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Med Klin & Poliklin 1, Ismaninger Str 22, D-81675 Munich, Germany. EM laugwitz@mytum.de FU German Research Foundation (Deutsche Forschungsgemeinschaft: initiative on major instrumentation), Research Unit 923 [La 1238 3-1/4-1]; European Research Council (ERC) [ERC-2011-ADG_20110310, ERC 261053]; DZHK (German Centre for Cardiovascular Research); Munich Heart Alliance; National Institutes of Health (NIH) [R01 HL096576]; German Research Foundation (DFG) [FOR 2033 GO 713/2-1, SFB 1243]; DJCLS [R 14/16] FX This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft: initiative on major instrumentation [funding for the installation of the positron emission tomography/magnetic resonance scanner]; Research Unit 923, La 1238 3-1/4-1 to Dr Laugwitz), by the European Research Council (ERC Grant MUMI, ERC-2011-ADG_20110310 to Dr Schwaiger and ERC 261053 to Dr Laugwitz), the DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, and the National Institutes of Health (NIH grant R01 HL096576 to Dr Nahrendorf). Dr Gotze was funded by the German Research Foundation (DFG: FOR 2033 GO 713/2-1 and SFB 1243) and the DJCLS R 14/16. NR 45 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD APR PY 2016 VL 9 IS 4 AR e004316 DI 10.1161/CIRCIMAGING.115.004316 PG 13 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DK3DG UT WOS:000374795700006 PM 27056601 ER PT J AU Wimmer, NJ Secemsky, EA Mauri, L Roe, MT Saha-Chaudhuri, P Dai, D McCabe, JM Resnic, FS Gurm, HS Yeh, RW AF Wimmer, Neil J. Secemsky, Eric A. Mauri, Laura Roe, Matthew T. Saha-Chaudhuri, Paramita Dai, David McCabe, James M. Resnic, Frederic S. Gurm, Hitinder S. Yeh, Robert W. TI Effectiveness of Arterial Closure Devices for Preventing Complications With Percutaneous Coronary Intervention An Instrumental Variable Analysis SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bleeding; complications; femoral artery; percutaneous coronary intervention; vascular closure devices ID BLEEDING AVOIDANCE STRATEGIES; CARDIOVASCULAR DATA REGISTRY; CARDIAC-CATHETERIZATION; VASCULAR COMPLICATIONS; FEMORAL-ARTERY; MANUAL COMPRESSION; COMPARATIVE SAFETY; CATHPCI REGISTRY; ACUITY TRIAL; PUNCTURE AB Background-Bleeding is associated with poor outcomes after percutaneous coronary intervention (PCI). Although arterial closure devices (ACDs) are widely used in clinical practice, whether they are effective in reducing bleeding complications during transfemoral PCI is uncertain. The objective of this study was to evaluate the effectiveness of ACDs for the prevention of vascular access site complications in patients undergoing transfemoral PCI using an instrumental variable approach. Methods and Results-We performed a retrospective analysis of the CathPCI Registry from 2009 to 2013 at 1470 sites across the United States. Variation in the proportion of ACDs used by each individual physician operator was used as an instrumental variable to address potential confounding. A 2-stage instrumental variable analysis was used as the primary approach. The main outcome measure was vascular access site complications, and nonaccess site bleeding was used as a falsification end point (negative control) to evaluate for potential confounding. A total of 1053155 ACDs were used during 2056585 PCIs during the study period. The vascular access site complication rate was 1.5%. In the instrumental variable analysis, the use of ACDs was associated with a 0.40% absolute risk reduction in vascular access site complications (95% confidence interval, 0.31-0.42; number needed to treat=250). Absolute differences in nonaccess site bleeding were negligible (risk difference, 0.04%; 95% confidence interval, 0.01-0.07), suggesting acceptable control of confounding in the comparison. Conclusions-ACDs are associated with a modest reduction in major bleeding after PCI. The number needed to treat with ACDs to prevent 1 major bleeding event is high. C1 [Wimmer, Neil J.] Christiana Care Hlth Syst, Div Cardiol, Dept Med, Newark, DE USA. [Secemsky, Eric A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Mauri, Laura] Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA 02115 USA. [Roe, Matthew T.; Dai, David] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Saha-Chaudhuri, Paramita] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. [McCabe, James M.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA. [Resnic, Frederic S.] Lahey Clin Fdn, Div Cardiol, Dept Med, Burlington, MA USA. [Gurm, Hitinder S.] Univ Michigan, Dept Med, Div Cardiol, Ann Arbor, MI 48109 USA. [Yeh, Robert W.] Beth Israel Deaconess Med Ctr, Dept Med, Smith Ctr Outcomes Res Cardiol, Boston, MA 02215 USA. RP Yeh, RW (reprint author), Harvard Univ, Dept Med, Smith Ctr Outcomes Res Cardiol, Beth Israel Deaconess Med Ctr,Med Sch, 185 Pilgrim Rd,Baker 4, Boston, MA 02215 USA. EM ryeh@bidmc.harvard.edu OI Gurm, Hitinder/0000-0002-1646-0218; Saha Chaudhuri, Paramita/0000-0003-1987-320X FU American College of Cardiology Foundation's National Cardiovascular Data Registry; National Heart, Lung and Blood Institute [1K23HL118138] FX This research was supported by the American College of Cardiology Foundation's National Cardiovascular Data Registry and by the National Heart, Lung and Blood Institute Grant 1K23HL118138 (R.W. Yeh). NR 27 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD APR PY 2016 VL 9 IS 4 AR e003464 DI 10.1161/CIRCINTERVENTIONS.115.003464 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK4KF UT WOS:000374886200011 PM 27059685 ER PT J AU Hussain, I Mohammed, SF Forfia, PR Lewis, GD Borlaug, BA Gallup, DS Redfield, MM AF Hussain, Imad Mohammed, Selma F. Forfia, Paul R. Lewis, Gregory D. Borlaug, Barry A. Gallup, Dianne S. Redfield, Margaret M. TI Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) Trial SO CIRCULATION-HEART FAILURE LA English DT Article DE diastole; exercise; heart failure; hypertension; pulmonary hypertension ID RANDOMIZED CONTROLLED-TRIAL; PLANE SYSTOLIC EXCURSION; VENTILATORY EFFICIENCY; CARDIAC STRUCTURE; OXYGEN-UPTAKE; HYPERTENSION; HEMODYNAMICS; 1-YEAR; DYSFUNCTION; PROGNOSIS AB Background Right ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function indexed to load (RV-pulmonary arterial [PA] coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV-PA coupling may be uniquely sensitive to sildenafil. Methods and Results In a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial, physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD (tricuspid annular plane systolic excursion [TAPSE]) and according to impairment in RV-PA coupling (TAPSE/pulmonary artery systolic pressure) ratio. The prevalence of atrial fibrillation and diuretic use, n-terminal probrain natriuretic peptide levels, renal dysfunction, neurohumoral activation, myocardial necrosis and fibrosis biomarkers, and the severity of diastolic dysfunction all increased with severity of RVD. Peak oxygen consumption decreased and ventilatory inefficiency (VE/VCO2 slope) increased with increasing severity of RVD. Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio. Compared with placebo, at 24 weeks, TAPSE decreased, and peak oxygen consumption and VE/CO2 slope were unchanged with sildenafil. There was no interaction between RV-PA coupling and treatment effect, and sildenafil did not improve TAPSE, peak oxygen consumption, or VE/VCO2 in patients with pulmonary hypertension and RVD. Conclusions HFpEF patients with RVD and impaired RV-PA coupling have more advanced heart failure. In RELAX patients with RVD and impaired RV-PA coupling, sildenafil did not improve RV function, exercise capacity, or ventilatory efficiency. C1 [Hussain, Imad; Mohammed, Selma F.; Borlaug, Barry A.; Redfield, Margaret M.] Mayo Clin, Div Cardiovasc Dis, 200 First St SW, Rochester, MN 55905 USA. [Forfia, Paul R.] Temple Univ, Philadelphia, PA 19122 USA. [Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Gallup, Dianne S.] Duke Clin Res Inst, Durham, NC USA. RP Redfield, MM (reprint author), Mayo Clin, Div Cardiovasc Dis, 200 First St SW, Rochester, MN 55905 USA. EM redfield.margaret@mayo.edu FU National Heart, Lung, and Blood Institute (NHLBI) [U10 HL084904, U01 HL084861, U10 HL110312, U109 HL110337, U01 HL084889, U01 HL084890, U01 HL084891, U10 HL110342, U10 HL110262, U01 HL084931, U10 HL110297, U10 HL110302, U10 HL110309, U10 HL110336, U10 HL110338] FX This work was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) (coordinating center: U10 HL084904; regional clinical centers: U01 HL084861, U10 HL110312, U109 HL110337, U01 HL084889, U01 HL084890, U01 HL084891, U10 HL110342, U10 HL110262, U01 HL084931, U10 HL110297, U10 HL110302, U10 HL110309, U10 HL110336, U10 HL110338). NR 29 TC 4 Z9 4 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD APR PY 2016 VL 9 IS 4 AR e002729 DI 10.1161/CIRCHEARTFAILURE.115.002729 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DK3DJ UT WOS:000374796000005 PM 27072860 ER PT J AU Hant, FN Bolster, MB AF Hant, Faye N. Bolster, Marcy B. TI Drugs that may harm bone: Mitigating the risk SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Review ID PROTON PUMP INHIBITORS; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; SEROTONIN REUPTAKE INHIBITORS; FRACTURE RISK; VERTEBRAL FRACTURE; BREAST-CANCER; POSTMENOPAUSAL WOMEN; ORAL CORTICOSTEROIDS; MINERAL DENSITY; HIP FRACTURE AB Glucocorticoids, proton pump inhibitors, selective serotonin reuptake inhibitors (SSRIs), certain antiepileptic drugs, and aromatase inhibitors have significant adverse effects on bone. Healthcare providers should monitor the bone health of patients on these agents, supplement their intake of calcium and vitamin D, encourage weight-bearing exercise, and initiate osteoporosis-prevention treatment as indicated. C1 [Hant, Faye N.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Bolster, Marcy B.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Bolster, Marcy B.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Hant, FN (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, Med, 96 Jonathan Lucas St,Suite 816, Charleston, SC 29425 USA. EM hant@musc.edu NR 49 TC 1 Z9 1 U1 3 U2 5 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 EI 1939-2869 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD APR PY 2016 VL 83 IS 4 BP 281 EP 288 DI 10.3949/ccjm.83a.15066 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DK3TV UT WOS:000374841200007 PM 27055202 ER PT J AU Rosenberg, AS Pariser, AR Diamond, B Yao, L Turka, LA Lacana, E Kishnani, PS AF Rosenberg, A. S. Pariser, A. R. Diamond, B. Yao, L. Turka, L. A. Lacana, E. Kishnani, P. S. TI A role for plasma cell targeting agents in immune tolerance induction in autoimmune disease and antibody responses to therapeutic proteins SO CLINICAL IMMUNOLOGY LA English DT Review DE Autoantibodies; Plasma cells; Immune tolerance; Enzyme replacement therapy ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; THROMBOTIC THROMBOCYTOPENIC PURPURA; INFANTILE POMPE DISEASE; MULTIPLE-MYELOMA; PROTEASOME INHIBITORS; NEUTRALIZING ANTIBODIES; GAUCHER-DISEASE; ENZYME THERAPY; FOLLOW-UP; BORTEZOMIB AB Antibody responses to life saving therapeutic protein products, such as enzyme replacement therapies (ERT) in the setting of lysosomal storage diseases, have nullified product efficacy and caused clinical deterioration and death despite treatment with immune-suppressive therapies. Moreover, in some autoimmune diseases, pathology is mediated by a robust antibody response to endogenous proteins such as is the case in pulmonary alveolar proteinosis, mediated by antibodies to Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). In this work, we make the case that in such settings, when the antibody response is high titered, sustained, and refractory to immune suppressive treatments, the antibody response is mediated by long-lived plasma cells which are relatively unperturbed by immune suppressants including rituximab. However, long-lived plasma cells can be targeted by proteasome inhibitors such as bortezomib. Recent reports of successful reversal of antibody responses with bortezomib in the settings of ERT and Thrombotic Thrombocytopenic Purpura (TTP) argue that the safety and efficacy of such plasma cell targeting agents should be evaluated in larger scale clinical trials to delineate the risks and benefits of such therapies in the settings of antibody-mediated adverse effects to therapeutic proteins and autoantibody mediated pathology. Published by Elsevier Inc. C1 [Rosenberg, A. S.; Lacana, E.] US FDA, Off Biotechnol Prod, CDER, Bldg 71-2238,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. [Pariser, A. R.] US FDA, Off Translat Sci, CDER, Silver Spring, MD 20993 USA. [Yao, L.] US FDA, Off New Drugs, CDER, Silver Spring, MD 20993 USA. [Turka, L. A.] Massachusetts Gen Hosp, East Transplantat Biol Res Ctr, 13th St,Bldg 149-9019, Boston, MA 02129 USA. [Diamond, B.] Feinstein Inst Med Res, Ctr Autoimmune & Musculoskeletal Dis, 350 Community Dr, Manhasset, NY 11030 USA. [Kishnani, P. S.] Duke Univ, Sch Med, 595 Lasalle St,GSRB 14th Floor,Room 4010, Durham, NC 27710 USA. RP Rosenberg, AS (reprint author), US FDA, Off Biotechnol Prod, CDER, Bldg 71-2238,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 45 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2016 VL 165 BP 55 EP 59 DI 10.1016/j.clim.2016.02.009 PG 5 WC Immunology SC Immunology GA DK8KU UT WOS:000375176400011 PM 26928739 ER PT J AU Fischer, ES Park, E Eck, MJ Thoma, NH AF Fischer, Eric S. Park, Eunyoung Eck, Michael J. Thomae, Nicolas H. TI SPLINTS: small-molecule protein ligand interface stabilizers SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID E3 UBIQUITIN LIGASE; CRYSTAL-STRUCTURE; GUANINE-NUCLEOTIDE; TYROSINE KINASE; BREFELDIN-A; BINDING DOMAIN; FKBP12-RAPAMYCIN COMPLEX; MAMMALIAN PROTEIN; HUMAN CALCINEURIN; MULTIPLE-MYELOMA AB Regulatory protein-protein interactions are ubiquitous in biology, and small molecule protein-protein interaction inhibitors are an important focus in drug discovery. Remarkably little attention has been given to the opposite strategy stabilization of protein-protein interactions, despite the fact that several well-known therapeutics act through this mechanism. From a structural perspective, we consider representative examples of small molecules that induce or stabilize the association of protein domains to inhibit, or alter, signaling for nuclear hormone, GTPase, kinase, phosphatase, and ubiquitin ligase pathways. These SPLINTS (small-molecule protein ligand interface stabilizers) drive interactions that are in some cases physiologically relevant, and in others entirely adventitious. The diverse structural mechanisms employed suggest approaches for a broader and systematic search for such compounds in drug discovery. C1 [Fischer, Eric S.; Thomae, Nicolas H.] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland. [Thomae, Nicolas H.] Univ Basel, Peterspl 10, CH-4003 Basel, Switzerland. [Fischer, Eric S.; Park, Eunyoung; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Fischer, Eric S.; Park, Eunyoung; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Fischer, ES; Thoma, NH (reprint author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.; Thoma, NH (reprint author), Univ Basel, Peterspl 10, CH-4003 Basel, Switzerland.; Fischer, ES; Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.; Fischer, ES; Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM eric_fischer@dfci.harvard.edu; eck@crystal.harvard.edu; nicolas.thoma@fmi.ch OI Fischer, Eric S./0000-0001-7337-6306 FU National Institutes of Health [GM110352, CA116020]; ERC [ERC-2014-ADG 666068]; Novartis Research Foundation FX MJE and EP are supported in part by Grants GM110352 and CA116020 from the National Institutes of Health. NHT is supported in part by a senior ERC Grant (ERC-2014-ADG 666068) and the Novartis Research Foundation. NR 56 TC 1 Z9 1 U1 2 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X EI 1879-033X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD APR PY 2016 VL 37 BP 115 EP 122 DI 10.1016/j.sbi.2016.01.004 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DK8FQ UT WOS:000375163000016 PM 26829757 ER PT J AU Irimia, D AF Irimia, D. TI Fast-food or sit-down dinner phagocytosis during human neutrophils traffic? SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Irimia, D.] Harvard Univ, Massachusetts Gen Hosp, Shriners Burns Hosp, BioMEMS Resource Ctr,Dept Surg,Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 EI 1365-2362 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 2016 VL 46 SU 1 SI SI MA 6.52 BP 85 EP 86 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DL1FO UT WOS:000375378000206 ER PT J AU Ferrari, G Nallasamy, N Downs, H Dana, R Oaklander, AL AF Ferrari, Giulio Nallasamy, Nambi Downs, Heather Dana, Reza Oaklander, Anne Louise TI Corneal innervation as a window to peripheral neuropathies (vol 113, pg 148, 2013) SO EXPERIMENTAL EYE RESEARCH LA English DT Correction C1 [Ferrari, Giulio; Nallasamy, Nambi; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Stamford St, Boston, MA 02114 USA. [Ferrari, Giulio] Ist Sci San Raffaele, Via Olgettina 60, I-20132 Milan, Italy. [Downs, Heather; Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 275 Charles St, Boston, MA 02114 USA. [Downs, Heather; Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol Neuropathol, 275 Charles St, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, 275 Charles St, Boston, MA 02114 USA. RP Ferrari, G (reprint author), Hosp San Raffaele, Eye Repair Lab, Cornea & Ocular Surface Unit, Via Olgettina 60, I-20122 Milan, Italy. EM giulio.ferrari@schepens.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD APR PY 2016 VL 145 BP 473 EP 473 DI 10.1016/j.exer.2016.01.005 PG 1 WC Ophthalmology SC Ophthalmology GA DL1DL UT WOS:000375372300055 ER PT J AU Shaye, DA AF Shaye, David A. TI Global Cleft Surgery SO FACIAL PLASTIC SURGERY LA English DT Article DE global surgery; cleft lip; cleft palate; cost-effectiveness ID CARE; DISEASE; HEALTH; BURDEN AB Surgery has recently been properly recognized as an essential component of global health. Global cleft surgery, often performed by visiting surgical teams in many parts of the world, has evolved with the recent surge in interest in global surgery. This article explores that evolution. C1 [Shaye, David A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. [Shaye, David A.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Shaye, David A.] Univ Rwanda, Coll Med & Hlth Sci, Ctr Hosp Univ Kigali, Dept Otolaryngol, Kigali, Rwanda. RP Shaye, DA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA.; Shaye, DA (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA.; Shaye, DA (reprint author), Univ Rwanda, Coll Med & Hlth Sci, Ctr Hosp Univ Kigali, Dept Otolaryngol, Kigali, Rwanda.; Shaye, DA (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, 243 Charles St,9th Fl, Boston, MA 02114 USA. EM dshaye@gmail.com NR 19 TC 0 Z9 0 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0736-6825 EI 1098-8793 J9 FACIAL PLAST SURG JI Facial Plast. Surg. PD APR PY 2016 VL 32 IS 2 BP 209 EP 212 DI 10.1055/s-0036-1582247 PG 4 WC Surgery SC Surgery GA DK3TC UT WOS:000374839300011 PM 27097142 ER PT J AU Kim, HY Tufano, RP Randolph, G Barczynski, M Wu, CW Chiang, FY Liu, XL Masuoka, H Miyauchi, A Park, SY Kwak, HY Lee, HY Dionigi, G AF Kim, Hoon Yub Tufano, Ralph P. Randolph, Gregory Barczynski, Marcin Wu, Che-Wei Chiang, Feng-Yu Liu, Xiaoli Masuoka, Hiroo Miyauchi, Akira Park, Soo Young Kwak, Hee Yong Lee, Hye Yoon Dionigi, Gianlorenzo CA Korean Intraoperative Neural TI Impact of positional changes in neural monitoring endotracheal tube on amplitude and latency of electromyographic response in monitored thyroid surgery: Results from the Porcine Experiment SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE thyroid; recurrent laryngeal nerve; electromyography; amplitude; latency ID RECURRENT LARYNGEAL NERVE; INJURY; STIMULATION; PLACEMENT AB Background. The purpose of this study was to evaluate electromyography (EMG) amplitude and latency changes during tube dislocation in monitored thyroid surgery, which may be observed without recurrent laryngeal nerve injury. Methods. Duroc-Landrace piglets were intubated with the TriVantage EMG tube. We measured EMG changes during both upward and downward tube dislocation (10-20 mm) and rotation (45-90 degrees) with continuous neuromonitoring. Results. The EMG amplitude varied significantly with induced endotracheal tube rotation and depth changes. However, the EMG latency was relatively unaffected by such tube dislocation, just a transient artifactual latency change was observed in the situation of extreme amplitude variation. Conclusion. Amplitude changes without latency changes may be due to changes in tube position alone during surgery, but could still reflect a neurophysiologic event; amplitude changes during neuropraxic injury merit additional investigation. Thus, the combined event (concordant amplitude decrease and latency increase) serves as an appropriate adverse EMG event correlating with impending neural injury. (c) 2015 Wiley Periodicals, Inc. C1 [Kim, Hoon Yub; Kwak, Hee Yong; Lee, Hye Yoon] Korea Univ, Coll Med, Korea Univ Anam Hosp, Dept Surg,KUMC Thyroid Ctr, Seoul 136705, South Korea. [Tufano, Ralph P.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Div Head & Neck Endocrine Surg, Baltimore, MD USA. [Randolph, Gregory] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Thyroid & Parathyroid Endocrine Surg,Dept Lar, Boston, MA USA. [Barczynski, Marcin] Jagiellonian Univ, Coll Med, Dept Gen Surg, Krakow, Poland. [Wu, Che-Wei; Chiang, Feng-Yu] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Coll Med, Inst Clin Med,Fac Med, Kaohsiung, Taiwan. [Wu, Che-Wei; Chiang, Feng-Yu] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Otolaryngol Head & Neck Surg, Kaohsiung, Taiwan. [Liu, Xiaoli] Jilin Univ, Japan Union Hosp, Jilin Prov Key Lab Surg Translat Med, Div Thyroid Surg, Changchun 130023, Jilin Province, Peoples R China. [Masuoka, Hiroo] Kuma Hosp, Ctr Excellence Thyroid Care, Dept Surg, Kobe, Hyogo, Japan. [Miyauchi, Akira; Park, Soo Young] Korea Univ, Coll Med, Dept Anesthesiol, Seoul 136705, South Korea. [Dionigi, Gianlorenzo] Univ Insubria Varese Como Varese, Dept Surg Sci & Human Morphol, Res Ctr Endocrine Surg, Div Gen Surg 1, Via Guicciardini 9, I-21100 Varese, Italy. RP Dionigi, G (reprint author), Univ Insubria Varese Como Varese, Dept Surg Sci & Human Morphol, Res Ctr Endocrine Surg, Div Gen Surg 1, Via Guicciardini 9, I-21100 Varese, Italy. EM gianlorenzo.dionigi@uninsubria.it OI dionigi, gianlorenzo/0000-0003-0864-6087; Wu, Che-Wei/0000-0003-1052-5348 NR 13 TC 3 Z9 3 U1 3 U2 4 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 APR PY 2016 VL 38 SU 1 BP E1004 EP E1008 DI 10.1002/hed.24145 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DK7OU UT WOS:000375116400125 PM 26040955 ER PT J AU Lorch, JH Hanna, GJ Posner, MR O'Neill, A Thotakura, VL Limaye, SA Rabinowits, G Sher, DJ Tishler, RB Haddad, RI AF Lorch, Jochen H. Hanna, Glenn J. Posner, Marshall R. O'Neill, Anne Thotakura, Vijaya L. Limaye, Sewanti A. Rabinowits, Guilherme Sher, David J. Tishler, Roy B. Haddad, Robert I. TI Human papillomavirus and induction chemotherapy versus concurrent chemoradiotherapy in locally advanced oropharyngeal cancer: The Dana Farber Experience SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE human papillomavirus (HPV); oropharyngeal; cancer; chemotherapy; treatment ID SQUAMOUS-CELL CARCINOMA; PHASE-III TRIAL; NECK-CANCER; PLUS CETUXIMAB; HEAD; SURVIVAL; RADIOTHERAPY; ONCOLOGY; THERAPY AB Background. Human papillomavirus (HPV) infection indicates favorable prognosis in oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was for us to assess the impact of HPV in patients treated with sequential therapy versus concomitant chemoradiotherapy (CRT). Methods. Patients with stage III and IVA and B oropharyngeal SCC were reviewed spanning 10 years. Results. Among 500 cases, 291 (58%) received CRT versus 209 (42%) sequential therapy. HPV status was known in 279 of patients (56%) and positive in 77% (determined by polymerase chain reaction [PCR; 91%], p16 immunohistochemical [IHC], or both). Median follow-up was 2.8 years. Overall survival (OS) did not differ for sequential therapy versus CRT overall (hazard ratio [HR] = 0.90; p = .66; 3-year OS = 86% and 87%) or within HPV-positive patients (HR = 0.89; p = .81; 3-year OS = 91% and 91%) or within HPV-negative patients (HR = 0.55; p = .32; 3-year OS = 85% and 75%). Conclusion. Survival for all patients was high and notable for HPV-negative patients treated with sequential therapy. Further studies in this patient population are warranted. (C) 2015 Wiley Periodicals, Inc. C1 [Lorch, Jochen H.; Hanna, Glenn J.; Thotakura, Vijaya L.; Limaye, Sewanti A.; Rabinowits, Guilherme; Haddad, Robert I.] Dana Farber Canc Inst, Dept Med Oncol, SW430,450 Brookline Ave, Boston, MA 02115 USA. [Posner, Marshall R.] Mt Sinai Sch Med, Dept Med Oncol, New York, NY USA. [O'Neill, Anne] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sher, David J.] Rush Presbyterian St Lukes Med Ctr, Dept Radiat Oncol, Chicago, IL USA. [Tishler, Roy B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Lorch, JH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, SW430,450 Brookline Ave, Boston, MA 02115 USA. EM Jochen_Lorch@dfci.harvard.edu NR 17 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD APR PY 2016 VL 38 SU 1 BP E1618 EP E1624 DI 10.1002/hed.24289 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DK7OU UT WOS:000375116400209 PM 26614576 ER PT J AU Mandal, R Duvvuri, U Ferris, RL Kaffenberger, TM Choby, GW Kim, S AF Mandal, Rajarsi Duvvuri, Umamaheswar Ferris, Robert L. Kaffenberger, Thomas M. Choby, Garret W. Kim, Seungwon TI Analysis of post-transoral robotic-assisted surgery hemorrhage: Frequency, outcomes, and prevention SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE transoral robotic-assisted surgery (TORS); TORS hemorrhage; TORS bleeding; TORS complications; prophylactic arterial ligation ID OBSTRUCTIVE SLEEP-APNEA; ASCENDING PHARYNGEAL ARTERY; SQUAMOUS-CELL CARCINOMA; FUNCTIONAL OUTCOMES; PARAPHARYNGEAL SPACE; CLINICAL-EXPERIENCE; HYPOPNEA SYNDROME; CAROTID-ARTERY; FEASIBILITY; OROPHARYNX AB Background. Transoral robotic-assisted surgery (TORS) carries a small, but not insignificant, risk of life-threatening postsurgical hemorrhage. The purpose of this study was to analyze all post-TORS hemorrhagic events at our institution to establish preventative recommendations. Methods. We conducted a retrospective review of 224 consecutive patients who underwent TORS for any indication at a single tertiary care institution. Results. Twenty-two patients (n = 22; 9.82%) had varying degrees of postoperative bleeding. An impaired ability to protect the airway at the time of hemorrhage increased the rate of severe complications. Prophylactic transcervical arterial ligation did not significantly decrease overall postoperative bleeding rates (9.1% vs 9.9%; p = 1.00); however, there was a trend toward decreased hemorrhage severity in prophylactically ligated patients (3.0% vs 7.3%; p = .7040). Conclusion. Prophylactic transcervical arterial ligation may reduce the incidence of severe bleeding following TORS. Post-TORS patients displaying an inability to protect the airway should be strongly considered for prophylactic tracheostomy to assist airway protection. (C) 2015 Wiley Periodicals, Inc. C1 [Mandal, Rajarsi; Duvvuri, Umamaheswar; Ferris, Robert L.; Choby, Garret W.; Kim, Seungwon] Univ Pittsburgh, Dept Otolaryngol, Med Ctr, Pittsburgh, PA 15260 USA. [Duvvuri, Umamaheswar] Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Kaffenberger, Thomas M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Kim, S (reprint author), Eye & Ear Inst Pittsburgh, Suite 500,203 Lothrop St, Pittsburgh, PA 15213 USA. EM kimsw2@upmc.edu NR 25 TC 5 Z9 5 U1 0 U2 0 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 APR PY 2016 VL 38 SU 1 BP E776 EP E782 DI 10.1002/hed.24101 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DK7OU UT WOS:000375116400093 PM 25916790 ER PT J AU Osazuwa-Peters, N Christopher, KM Hussaini, AS Behera, A Walker, RJ Varvares, MA AF Osazuwa-Peters, Nosayaba Christopher, Kara M. Hussaini, Adnan S. Behera, Anit Walker, Ronald J. Varvares, Mark A. TI Predictors of stage at presentation and outcomes of head and neck cancers in a university hospital setting SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE head and neck cancer; stage at presentation; health insurance status; race; outcomes ID SQUAMOUS-CELL CARCINOMA; HEALTH-INSURANCE STATUS; ORAL-CANCER; OROPHARYNGEAL CANCER; FACIAL DISFIGUREMENT; HUMAN-PAPILLOMAVIRUS; FINANCIAL TOXICITY; MARITAL-STATUS; UNITED-STATES; DIAGNOSIS AB Background. To increase early detection of head and neck cancers, it is important that disparities associated with access to care are addressed. Methods. A total of 351 patients aged 20 to 91 years (58.72 +/- 11.70 years) diagnosed with head and neck cancers at a university hospital from 1997 to 2010 were analyzed. Logistic regression assessed the association between clinical stage at presentation and predictors. Cox proportional hazards model assessed the effect of stage at presentation on survival. Results. Being African American was associated with increased odds of late stage at presentation (adjusted odds ratio [OR] = 2.16; 95% confidence interval [CI] = 1.01-4.59), and those without health insurance were 10.97 times more likely to present at late stage (95% CI = 1.30-92.49). Unmarried patients were 1.6 times at an increased hazard of death (95% CI = 1.12-2.24). Conclusion. Disparities, such as race and health insurance status, are important predictors of stage at presentation of patients with head and neck cancer. (C) 2015 Wiley Periodicals, Inc. C1 [Osazuwa-Peters, Nosayaba] St Louis Univ, Ctr Canc, St Louis, MO 63110 USA. [Osazuwa-Peters, Nosayaba; Christopher, Kara M.; Walker, Ronald J.; Varvares, Mark A.] St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 3635 Vista Ave,6th Floor Desloge Towers, St Louis, MO 63110 USA. [Hussaini, Adnan S.; Behera, Anit] St Louis Univ, Sch Med, St Louis, MO 63110 USA. [Behera, Anit] St Louis Univ, Ctr Outcomes Res, St Louis, MO 63110 USA. [Varvares, Mark A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. [Osazuwa-Peters, Nosayaba] St Louis Univ, Dept Epidemiol, Coll Publ Hlth & Social Justice, St Louis, MO 63110 USA. RP Osazuwa-Peters, N (reprint author), St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 3635 Vista Ave,6th Floor Desloge Towers, St Louis, MO 63110 USA. EM nosazuwa@slu.edu NR 59 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD APR PY 2016 VL 38 SU 1 BP E1826 EP E1832 DI 10.1002/hed.24327 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DK7OU UT WOS:000375116400237 PM 26695355 ER PT J AU Puram, SV Chow, H Wu, CW Heaton, JT Kamani, D Gorti, G Chiang, FY Dionigi, G Barczynski, M Schneider, R Dralle, H Lorenz, K Randolph, GW AF Puram, Sidharth V. Chow, Harold Wu, Che-Wei Heaton, James T. Kamani, Dipti Gorti, Gautham Chiang, Feng Yu Dionigi, Gianlorenzo Barczynski, Marcin Schneider, Rick Dralle, Henning Lorenz, Kerstin Randolph, Gregory W. TI Vocal cord paralysis predicted by neural monitoring electrophysiologic changes with recurrent laryngeal nerve compressive neuropraxic injury in a canine model SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE recurrent laryngeal nerve; injury; endocrine; thyroid surgery; vocal cord palsy; intraoperative nerve monitoring (IONM) ID THYROID-SURGERY; THYROARYTENOID MUSCLES; PARATHYROID SURGERY; PITFALLS; ELECTROMYOGRAPHY; COMPLICATIONS; INNERVATION; PLAUDITS; VAGAL AB Background. Recurrent laryngeal nerve (RLN) injury is a known complication of thyroid/parathyroid surgery. Intraoperative nerve monitoring (IONM) has been used to gain more information regarding the functional status of the RLN intraoperatively; however, the electromyography (EMG) parameters of RLN after nontransection neuropraxic compressive injury remain unknown. Methods. We developed a canine model to identify IONM EMG correlates of postoperative vocal cord paralysis (VCP) using a standardized method to simulate surgical RLN compression sufficient to cause VCP. Results. Compression nerve injury decreased EMG amplitude and increased EMG latency, with a 60% increase in RLN threshold stimulation compared to preinjury values. If RLN amplitude decreases by 80% with an absolute amplitude of 300 mu V or less in combination with a latency increase of 10% or more, then nerve injury and associated VCP is likely. Conclusion. These results may help surgeons to prognosticate postoperative neural function and intraoperative decision-making regarding contralateral thyroid surgery. (C) 2015 Wiley Periodicals, Inc. C1 [Puram, Sidharth V.; Chow, Harold; Wu, Che-Wei; Kamani, Dipti; Gorti, Gautham; Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Thyroid & Parathyroid Surg, 243 Charles St, Boston, MA 02114 USA. [Puram, Sidharth V.; Chow, Harold; Wu, Che-Wei; Heaton, James T.; Kamani, Dipti; Gorti, Gautham; Randolph, Gregory W.] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Che-Wei; Chiang, Feng Yu] Kaohsiung Med Univ, Dept Otorhinolaryngol Head & Neck Surg, Fac Med, Kaohsiung Med Univ Hosp,Coll Med, Kaohsiung, Taiwan. [Heaton, James T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Dionigi, Gianlorenzo] Univ Insubria, Sch Med, Dept Surg Sci & Human Morphol, Div Surg, Varese, Italy. [Barczynski, Marcin] Jagiellonian Univ, Coll Med, Dept Endocrine Surg, Krakow, Poland. [Schneider, Rick; Dralle, Henning; Lorenz, Kerstin] Univ Halle Wittenberg, Dept Gen Visceral & Vasc Surg, D-06108 Halle, Saale, Germany. [Randolph, Gregory W.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Thyroid & Parathyroid Endocrine Surg Div, 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu OI dionigi, gianlorenzo/0000-0003-0864-6087; Wu, Che-Wei/0000-0003-1052-5348 FU John and Claire Bertucci Thyroid Research fund FX Contract grant sponsor: The John and Claire Bertucci Thyroid Research fund supported the research for this study. NR 30 TC 6 Z9 6 U1 1 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 APR PY 2016 VL 38 SU 1 BP E1341 EP E1350 DI 10.1002/hed.24225 PG 10 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DK7OU UT WOS:000375116400172 PM 26348472 ER PT J AU Yarlagadda, BB Deschler, DG Rich, DL Lin, DT Emerick, KS Rocco, JW Durand, ML AF Yarlagadda, Bharat B. Deschler, Daniel G. Rich, Debbie L. Lin, Derrick T. Emerick, Kevin S. Rocco, James W. Durand, Marlene L. TI Head and neck free flap surgical site infections in the era of the Surgical Care Improvement Project SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE microvascular reconstruction; free flap; surgical site infection; head and neck cancer; antibiotic prophylaxis ID RECONSTRUCTIVE SURGERY; MICROVASCULAR HEAD; RISK-FACTORS; COMPLICATIONS; CANCER; PROPHYLAXIS; ANTIBIOTICS; PREVENTION; OUTCOMES AB Background. Compliance with Surgical Care Improvement Project (SCIP) parameters regarding antibiotic prophylaxis may affect surgical site infection rates. The purpose of this study was for us to report SCIP compliance, surgical site infection rates, and risk factors in a large series of head and neck free flap surgeries. Methods. A retrospective review of 480 free flap cases was performed. Surgical site infections occurring within 30 days postoperatively were noted. Results. Surgical site infection occurred in 13.3% of cases. Prophylaxis was given in 99.8% of cases; ampicillin-sulbactam (83%) and clindamycin (9%) were most common. Prophylaxis was "on-time" in 92.3% of cases. There were no significant associations between surgical site infection and tumor stage, American Society of Anesthesiologists (ASA) classification, tumor subsite, or flap type. Prior radiation was a risk factor for surgical site infection in patients treated for malignancy. Conclusion. A surgical site infection rate of 13.3% was noted. In this cohort, with a compliance rate with prophylactic antibiotic measures, prior radiation was found to be a risk factor only in patients with cancer. (C) 2015 Wiley Periodicals, Inc. C1 [Yarlagadda, Bharat B.; Deschler, Daniel G.; Lin, Derrick T.; Emerick, Kevin S.; Rocco, James W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Rich, Debbie L.] Massachusetts Eye & Ear Infirm, Dept Nursing, Boston, MA 02114 USA. [Durand, Marlene L.] Massachusetts Eye & Ear Infirm, Infect Dis Serv, 243 Charles St, Boston, MA 02114 USA. [Durand, Marlene L.] Massachusetts Gen Hosp, Dept Med, 243 Charles St, Boston, MA 02114 USA. RP Durand, ML (reprint author), Massachusetts Eye & Ear Infirm, Infect Dis Serv, 243 Charles St, Boston, MA 02114 USA.; Durand, ML (reprint author), Massachusetts Gen Hosp, Dept Med, 243 Charles St, Boston, MA 02114 USA. EM mdurand@mgh.harvard.edu NR 30 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD APR PY 2016 VL 38 SU 1 BP E392 EP E398 DI 10.1002/hed.24005 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DK7OU UT WOS:000375116400037 PM 25641048 ER PT J AU Lehmann, L El-Haddad, A Barr, RD AF Lehmann, Leslie El-Haddad, Alaa Barr, Ronald D. TI Global Approach to Hematologic Malignancies SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review DE Global; Low- and middle-income countries (LMIC); Hematologic malignancies; Leukemia; Lymphoma; Pediatric ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; TREATMENT-RELATED MORTALITY; EPSTEIN-BARR-VIRUS; CLASSICAL HODGKINS LYMPHOMA; LOW-INCOME COUNTRIES; PEDIATRIC-ONCOLOGY; CHILDHOOD LEUKEMIA; BURKITT-LYMPHOMA; CENTRAL-AMERICA AB Treatment of childhood hematologic malignancies requires multidisciplinary care and reliable infrastructural support; creating this structure in., resource-poor settings remains challenging. Ideally, therapy would be tailored to each region and disease. The development of research initiatives is essential. Acute lymphoblastic leukemia (ALL) and lymphomas are common in low- and middle-income countries; treatment is often resource-intensive but likely cost effective. Outcomes currently are worse than those reported in high-income countries. Chronic myeloid leukemia can be treated effectively with imatinib. Strategies to decrease the burden of therapy and robust palliative care programs are essential for optimal treatment of all afflicted children. C1 [Lehmann, Leslie] Harvard Univ, Sch Med, Dana Farber Canc Inst, Pediat Stem Cell Transplant, 450 Brookline Ave, Boston, MA 02115 USA. [El-Haddad, Alaa] Dept Pediat Oncol, 1 Fostat St, Cairo 11757, Egypt. [Barr, Ronald D.] McMaster Univ, Dept Pediat Oncol, 1200 Main St W, Hamilton, ON L8S 4J9, Canada. RP Lehmann, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Pediat Stem Cell Transplant, 450 Brookline Ave, Boston, MA 02115 USA. EM Leslie_Lehmann@DFCI.Harvard.edu NR 77 TC 0 Z9 0 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2016 VL 30 IS 2 BP 417 EP + DI 10.1016/j.hoc.2015.11.008 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA DK9FW UT WOS:000375237200010 PM 27040962 ER PT J AU Mellema, JJ Doornberg, JN Molenaars, RJ Ring, D Kloen, P AF Mellema, Jos J. Doornberg, Job N. Molenaars, Rik J. Ring, David Kloen, Peter CA Traumaplatform Study Collaborative TI Interobserver reliability of the Schatzker and Luo classification systems for tibial plateau fractures SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Tibial plateau fractures; Interobserver reliability; Classification; Schatzker; Luo; Computed tomography ID 3-DIMENSIONAL COMPUTED-TOMOGRAPHY; DIAGNOSTIC-ACCURACY; TUBERCLE FRACTURES; POSTERIOR APPROACH; HUMERAL FRACTURES; HIGH AGREEMENT; LOW KAPPA; CT; MANAGEMENT; RECONSTRUCTIONS AB Introduction: Tibial plateau fracture classification systems have limited interobserver reliability and new systems emerge. The purpose of this study was to compare the reliability of the Luo classification and the Schatzker classification for two-dimensional computed tomography (2DCT) and to study the effect of adding three-dimensional computed tomography (3DCT). Materials and Methods: > Eighty-one observers, orthopedic surgeons and residents, were randomized to either 2DCT or 2D-and 3DCT evaluation of a spectrum of 15 complex tibial plateau fractures using webbased platforms in order to classify according to the Schatzker and according to Luo's Three Column classification. Reliability was calculated with the use of Siegel and Castellan's multirater kappa measure. Kappa values were interpreted according to the categorical rating by Landis and Koch. Results: Overall interobserver reliability of the Schatzker classification was significantly better compared to the Luo classification (k(Schatzker) = 0.32 and k(Luo) = 0.28, P = 0.021), however, 'fair' for both fracture classification systems. For the Schatzker classification observers agreed significantly better on 2DCT compared to 2D-and 3DCT (k(2DCT) = 0.37 and k(2D+3DCT) = 0.29, P < 0.001). The addition of 3DCT did not improve the overall interobserver reliability for the Luo classification as well, as kappa values were not significantly different on 2DCT and 2D-and 3DCT (k(2DCT) = 0.31 and k(2D+3DCT) = 0.25, P = 0.096). Conclusions: The agreement between observers was significantly better for the Schatzker classification compared to Luo's Three Column classification, however agreement was fair for both classification systems. Furthermore, the addition of 3DCT reconstructions did not improve the reliability of CT-based evaluation of tibial plateau fractures. Considering that new classification systems and 3DCT do not seem to improve agreement between surgeons, other efforts are needed that lead to more reliable diagnosis of complex tibial plateau fractures. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Mellema, Jos J.; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Doornberg, Job N.; Molenaars, Rik J.; Kloen, Peter] Acad Med Ctr Amsterdam, Dept Orthoped Surg, Amsterdam, Netherlands. [Mellema, Jos J.; Ring, David] Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. [Doornberg, Job N.; Molenaars, Rik J.; Kloen, Peter] Univ Amsterdam, Acad Med Ctr, Dept Orthoped Surg, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands. RP Mellema, JJ (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.; Mellema, JJ (reprint author), Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM josjmellema@gmail.com; jobdoornbergortho@gmail.com; rik.molenaars@gmail.com; dring@mgh.harvard.edu; p.kloen@amc.uva.nl OI Swiontkowski, Marc/0000-0001-7036-1782 NR 45 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD APR PY 2016 VL 47 IS 4 BP 944 EP 949 DI 10.1016/j.injury.2015.12.022 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA DK6SV UT WOS:000375056400029 PM 26777468 ER PT J AU Riedel, MD Gonzalez, T Kwon, JY AF Riedel, Matthew D. Gonzalez, Tyler Kwon, John Y. TI How much is too much? A guide to appropriately bending ball tip guide wires when using intramedullary nails for the treatment of lower extremity long bone fractures SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Surgical technique; Long bone fracture; Ball tip guide wire; Intramedullary nail; Implant complications AB Introduction: This study was to determine the angle of bend that can be placed in a ball-tip guide wire while still allowing passage of reamers and nails of several commonly utilized nailing systems. Methods: Ball-tip guide wires, opening reamer tips, femoral nails, and tibial nails were collected from several manufacturers. Guide wires were incrementally bent 3 cm from the tip and passed through the reamer tip, tibial nail, and femoral nail until unable to pass. Results: All systems tested demonstrated that the reamer, with its relative smaller diameter cannula as compared to the nails themselves, determined the smallest tolerable bend to be able to pass the bent guide wire. The bend angle tolerated by reamer tips was on average 78 (4-98). The bend angle tolerated by femoral nails was more consistent between the tested systems and was on average 15.58 (12-188). The bend angle tolerated by tibial nails had the most variability between manufacturers and was on average 168 (13-218). Discussion: Knowing the degree of guide wire bend which is tolerated can save time in equipment preparation as well as allow one to pre-bend the guide wire and know the intramedullary nail and/or reamers will likely pass. We hope the information provided in this work increases awareness of the potential technical issues with guide wire over-bending and that surgeons may err on the side of minimizing the bend in order to save time in the OR, decrease frustration and eliminate intraoperative complications that can occur. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Riedel, Matthew D.; Gonzalez, Tyler] Harvard Univ, Sch Med, Harvard Combined Orthopaed Residency Program, Boston, MA USA. [Kwon, John Y.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Boston, MA 02215 USA. RP Riedel, MD (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Suite 535, Boston, MA 02115 USA. EM mdriedel@partners.org OI Riedel, Matthew/0000-0001-6640-7071 NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD APR PY 2016 VL 47 IS 4 BP 954 EP 957 DI 10.1016/j.injury.2015.12.023 PG 4 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA DK6SV UT WOS:000375056400031 PM 26776464 ER PT J AU Scales, CD Moin, T Fink, A Berry, SH Afsar-Manesh, N Mangione, CM Kerfoot, BP AF Scales, Charles D., Jr. Moin, Tannaz Fink, Arlene Berry, Sandra H. Afsar-Manesh, Nasim Mangione, Carol M. Kerfoot, B. Price TI A randomized, controlled trial of team-based competition to increase learner participation in quality-improvement education SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE graduate medical education; randomized controlled trial; quality improvement; spaced education ID INTERACTIVE SPACED-EDUCATION; WEIGHT-LOSS; MEMORY; ENVIRONMENT; INCENTIVES; RETENTION; RETRIEVAL; PROGRAM; IMPACT; SAFETY AB Several barriers challenge resident engagement in learning quality improvement (QI). We investigated whether the incorporation of team-based game mechanics into an evidence-based online learning platform could increase resident participation in a QI curriculum. Randomized, controlled trial. Tertiary-care medical center residency training programs. Resident physicians (n = 422) from nine training programs (anesthesia, emergency medicine, family medicine, internal medicine, ophthalmology, orthopedics, pediatrics, psychiatry and general surgery) randomly allocated to a team competition environment (n = 200) or the control group (n = 222). Specialty-based team assignment with leaderboards to foster competition, and alias assignment to de-identify individual participants. Participation in online learning, as measured by percentage of questions attempted (primary outcome) and additional secondary measures of engagement (i.e. response time). Changes in participation measures over time between groups were assessed with a repeated measures ANOVA framework. Residents in the intervention arm demonstrated greater participation than the control group. The percentage of questions attempted at least once was greater in the competition group (79% [SD +/- 32] versus control, 68% [SD +/- 37], P= 0.03). Median response time was faster in the competition group (P= 0.006). Differences in participation continued to increase over the duration of the intervention, as measured by average response time and cumulative percent of questions attempted (each P < 0.001). Team competition increases resident participation in an online course delivering QI content. Medical educators should consider game mechanics to optimize participation when designing learning experiences. C1 [Scales, Charles D., Jr.; Fink, Arlene; Mangione, Carol M.] Univ Calif Los Angeles, Robert Wood Johnson Fdn, US Dept Vet Affairs, Clin Scholars Program, Los Angeles, CA USA. [Scales, Charles D., Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Scales, Charles D., Jr.; Moin, Tannaz; Fink, Arlene; Afsar-Manesh, Nasim; Mangione, Carol M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Scales, Charles D., Jr.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Moin, Tannaz] Vet Affairs Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence Study Healthcare Innovat Imp, Los Angeles, CA USA. [Fink, Arlene; Mangione, Carol M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Berry, Sandra H.] RAND Corp, Santa Monica, CA USA. [Afsar-Manesh, Nasim] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA. [Kerfoot, B. Price] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Kerfoot, B. Price] Harvard Univ, Sch Med, Boston, MA USA. [Scales, Charles D., Jr.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Scales, Charles D., Jr.] Duke Univ, Sch Med, Div Urol Surg, Durham, NC USA. RP Scales, CD (reprint author), Duke Clin Res Inst, DUMC 3707, Durham, NC 27710 USA.; Scales, CD (reprint author), Div Urol Surg, DUMC 3707, Durham, NC 27710 USA. EM chuck.scales@duke.edu NR 30 TC 3 Z9 3 U1 3 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 EI 1464-3677 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD APR 1 PY 2016 VL 28 IS 2 BP 227 EP 232 DI 10.1093/intqhc/mzw008 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DK7GU UT WOS:000375094000011 PM 26857941 ER PT J AU Criss, S Cheung, LL Giles, C Gortmaker, S Viswanath, K Kwass, JA Davison, K AF Criss, Shaniece Cheung, Lilian Giles, Catherine Gortmaker, Steven Viswanath, Kasisomayajula Kwass, Jo-Ann Davison, Kirsten TI Media Competition Implementation for the Massachusetts Childhood Obesity Research Demonstration Study (MA-CORD): Adoption and Reach SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE media competition; elementary school; implementation; reach; adoption; childhood obesity ID SCHOOL-BASED INTERVENTIONS; CHILDREN; HEALTH; DISSEMINATION; TRANSLATION; FRAMEWORK; PROJECT AB The Massachusetts Childhood Obesity Research Demonstration Study (MA-CORD) was a multi-level, multi-sector community intervention with a media competition component to provide an overarching synergy and promote awareness of target behaviors to reduce childhood obesity. Students participating in the media competition were tasked with developing videos, song/rap lyrics, and artwork that reflected the goals. The aim of this study is to document the process used to develop and implement the media competition along with its reach and adoption. An adapted version of Neta and colleagues' 2015 framework on dissemination and implementation was used to summarize the process by which the media competition was developed and implemented. Adoption was defined by whether eligible schools or afterschool programs decided to implement the media competition. Reach was defined by student participation rates within schools/programs and the number of votes cast for the finalists on the coalition website and students' paper ballots. A total of 595 students participated in the media competition from 18 school and afterschool programs in two communities. Adoption of the media competitions ranged from 22% to 100% in programs and reach ranged from 3% to 33% of the student population. The documentation of the implementation should contribute to the replication of the media competition. C1 [Criss, Shaniece; Giles, Catherine; Gortmaker, Steven; Viswanath, Kasisomayajula; Davison, Kirsten] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave,Kresge Bldg, Boston, MA 02115 USA. [Cheung, Lilian; Davison, Kirsten] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Kwass, Jo-Ann] Massachusetts Dept Publ Hlth, Bur Community Hlth & Prevent, 250 Washington St, Boston, MA 02108 USA. RP Criss, S (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave,Kresge Bldg, Boston, MA 02115 USA. EM scriss@mail.harvard.edu; lcheung@hsph.harvard.edu; cgiles@hsph.harvard.edu; sgortmak@hsph.harvard.edu; vish_viswanath@dfci.harvard.edu; jo-ann.kwass@state.ma.us; kdavison@hsph.harvard.edu FU Centers for Disease Control and Prevention (CDC), National Center for Chronic Disease Prevention and Health Promotion [U18DP003370]; NIH [3R25CA057711]; Maternal and Child Health Bureau Award [T03MC07648]; Initiative to Maximize Student Diversity Award [GM055353-13] FX The authors want to thank Suzanne Crowther, MPH; Denise M. Gaudette, M.Ed.; Pamela Rivers, RN, MPH; and Debra Mayo, RN for their tremendous work on the MA-CORD Media Competition. The MA-CORD study was supported by the Centers for Disease Control and Prevention (CDC), National Center for Chronic Disease Prevention and Health Promotion (Award # U18DP003370). This study was also supported by predoctoral training grants from NIH Award # 3R25CA057711 (SC), the Initiative to Maximize Student Diversity Award # GM055353-13 (SC); and Maternal and Child Health Bureau Award #T03MC07648 (SC). Its contents are solely the responsibility of the author and do not necessarily represent the official views of the listed funding sources. NR 26 TC 2 Z9 2 U1 2 U2 3 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD APR PY 2016 VL 13 IS 4 AR 403 DI 10.3390/ijerph13040403 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA DK9DR UT WOS:000375231300051 PM 27058549 ER PT J AU Criss, S Tran, A Ganter, C Aftosmes-Tobio, A Gortmaker, S Viswanath, K Kwass, JA Davison, KK AF Criss, Shaniece Tran, Alvin Ganter, Claudia Aftosmes-Tobio, Alyssa Gortmaker, Steven Viswanath, Kasisomayajula Kwass, Jo-Ann Davison, Kirsten K. TI A Cascade of Champions: A Qualitative Study about the MA-CORD Media Competition Implementation SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE media competition; elementary school; implementation; qualitative; ecological framework for understanding effective implementation ID CHILDHOOD OBESITY; SCHOOL; PROJECT; AGREEMENT; PROGRAMS; FIDELITY; OUTCOMES; YOUTH AB A media competition was part of the Massachusetts Childhood Obesity Research Demonstration (MA-CORD) Study. Criss et al., previously outlined the development and implementation of the competition, including variation in reach and adoption of the intervention across schools and afterschool programs. In this qualitative study, we examine community, provider, and organizational factors that explain the variation of media competition reach in school and afterschool programs, and describe the awareness of the media competition across other community sectors. Durlak and DuPre's ecological framework for understanding effective implementation provided the theoretical underpinnings for this study. Fifty-four key informant interviews were conducted, transcribed, and analyzed. Organizational capacity of committed teachers/staff and adaptability of the media competition seemed to be drivers for higher reach within school and afterschool programs. Salient themes that emerged as facilitators of effective implementation were having a cascade of champions and providing opportunity to participate in the media competition outside traditional class time. Clinics and coalitions were identified as additional sectors aware of the media competition. Specifically, our findings offer a new perspective on intervention design and a recommended direction for further study. C1 [Criss, Shaniece; Gortmaker, Steven; Viswanath, Kasisomayajula; Davison, Kirsten K.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave,Kresge Bldg, Boston, MA 02115 USA. [Tran, Alvin; Ganter, Claudia; Aftosmes-Tobio, Alyssa; Davison, Kirsten K.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Kwass, Jo-Ann] Massachusetts Dept Publ Hlth, Bur Community Hlth & Prevent, 250 Washington St, Boston, MA 02108 USA. RP Criss, S (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave,Kresge Bldg, Boston, MA 02115 USA. EM scriss@mail.harvard.edu; alvintran@mail.harvard.edu; cgehre@hsph.harvard.edu; aaftosme@hsph.harvard.edu; sgortmak@hsph.harvard.edu; vish_viswanath@dfci.harvard.edu; jo-ann.kwass@state.ma.us; kdavison@hsph.harvard.edu OI Criss, Shaniece/0000-0002-2470-5377 FU Centers for Disease Control and Prevention (CDC), National Center for Chronic Disease Prevention and Health Promotion [U18DP003370]; NIH [3R25CA057711]; Initiative to Maximize Student Diversity Award [GM055353-13]; Maternal and Child Health Bureau Award [T03MC07648] FX The MA-CORD study was supported by the Centers for Disease Control and Prevention (CDC), National Center for Chronic Disease Prevention and Health Promotion (Award No. U18DP003370). This study was also supported by predoctoral training grants from NIH Award No. 3R25CA057711 (SC), the Initiative to Maximize Student Diversity Award No. GM055353-13 (SC); and Maternal and Child Health Bureau Award No. T03MC07648 (SC). Its contents are solely the responsibility of the author and do not necessarily represent the official views of the listed funding sources. NR 25 TC 0 Z9 0 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD APR PY 2016 VL 13 IS 4 AR 404 DI 10.3390/ijerph13040404 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA DK9DR UT WOS:000375231300052 PM 27058550 ER PT J AU Pendleton, AA Natarajan, A Ahn, R Nelson, BD Eckardt, MJ Burke, TF AF Pendleton, Anna Alaska Natarajan, Abirami Ahn, Roy Nelson, Brett D. Eckardt, Melody J. Burke, Thomas F. TI Emergency hysterectomy for uncontrolled postpartum hemorrhage may be averted through uterine balloon tamponade in Kenya and Senegal SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Editorial Material DE Emergency hysterectomy; Kenya; Maternal mortality; Senegal; Uterine balloon tamponade; Postpartum hemorrhage C1 [Pendleton, Anna Alaska; Natarajan, Abirami; Ahn, Roy; Nelson, Brett D.; Eckardt, Melody J.; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Pendleton, Anna Alaska; Natarajan, Abirami; Ahn, Roy; Nelson, Brett D.; Burke, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA. [Eckardt, Melody J.] Boston Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. [Eckardt, Melody J.] Boston Univ, Boston, MA 02215 USA. RP Burke, TF (reprint author), Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Zero Emerson Pl,Suite 104, Boston, MA 02114 USA. EM Tfburke@partners.org OI Nelson, Brett/0000-0002-5049-1798 NR 4 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 0020-7292 EI 1879-3479 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD APR PY 2016 VL 133 IS 1 BP 124 EP 124 DI 10.1016/j.ijgo.2015.09.006 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DJ7CT UT WOS:000374370200028 PM 26797194 ER PT J AU Li, XL Wilson, M Nylander, W Smith, T Lynn, M Gunnar, W AF Li, Xinli Wilson, Mark Nylander, William Smith, Tracy Lynn, Marilyn Gunnar, William TI Analysis of Morbidity and Mortality Outcomes in Postoperative Clostridium difficile Infection in the Veterans Health Administration SO JAMA SURGERY LA English DT Article ID RISK-FACTORS; TRANSPLANT RECIPIENTS; SURGERY; PROPHYLAXIS; OUTBREAK; DIARRHEA; COLITIS; IMPACT AB IMPORTANCE This study analyzes and reports Clostridium difficile infection (CDI) rates, risk factors, and associations with postoperative outcomes in the Veterans Health Administration (VHA). OBJECTIVE To report 30-day postoperative CDI rates and outcomes and identify associated risks by surgical procedures and preoperative patient demographics in a large integrated health care system. DESIGN, SETTING, AND PARTICIPANTS In a retrospective observational study conducted from September 2014 to April 2015, the Veterans Affairs Surgical Quality Improvement Program database and the Decision Support System pharmacy database were linked to analyze the association of postoperative CDI with patients' demographics, preoperative comorbidities, operative characteristics, and preoperative medications. The Veterans Affairs Surgical Quality Improvement Program assessments from October 1, 2009, to September 30, 2013, were investigated. The study was conducted at 134 VHA surgery programs, and the study population represents 12 surgical specialties: general, gynecological, neurosurgical, oral, orthopedics, otolaryngologic, plastic, podiatric, thoracic, transplant, urologic, and peripheral vascular. MAIN OUTCOMES AND MEASURES Thirty-day postoperative CDI rates, risk factors of CDI, and association of CDI with postoperative morbidity and mortality. RESULTS Among 468 386 surgical procedures, the postoperative CDI rate was 0.4% per year and varied by the VHA Surgery Program (0.0% to 1.4%) and surgical specialty (0.0% to 2.4%). Thirty-day CDI rates were higher in emergency procedures, procedures with greater complexity and higher relative value units, and those with a contaminated/ infected wound classification. Patients with postoperative CDI were significantly older, more frequently hospitalized after surgery (59.9% vs 15.4%), had longer preoperative hospital stays (9.1 days vs 1.9 days), and had received 3 or more classes of antibiotics (1.5% vs 0.3% for a single antibiotic class) (all P < .001). Patients with CDI had higher rates of other postoperative morbidity (86.0% vs 7.1%), 30-day mortality (5.3% vs 1.0%), and longer postoperative hospital stays (17.9 days vs 3.6 days). Independent risk factors for CDI included commonly identified patient factors (albumin, functional class, and weight loss), procedural characteristics (complexity, relative value units, emergency, and wound classification), surgical program complexity, the number of preoperative antibiotic classes, and length of preoperative hospital stay. CONCLUSIONS AND RELEVANCE The number and class of antibiotics administered after surgery, preoperative length of stay, procedural characteristics, surgical program complexity, and patient comorbidities are associated with postoperative CDI in the VHA. C1 [Li, Xinli; Wilson, Mark; Nylander, William; Smith, Tracy; Lynn, Marilyn; Gunnar, William] Vet Hlth Adm, Natl Surg Off, Washington, DC USA. [Wilson, Mark] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Wilson, Mark] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Gunnar, William] George Washington Univ, Washington, DC USA. RP Li, XL (reprint author), Vet Hlth Adm, Natl Surg Off, 4100 E Mississippi Ave,Ste 310, Glendale, CO 80246 USA. EM xinli.li2@va.gov NR 24 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD APR PY 2016 VL 151 IS 4 BP 314 EP 322 DI 10.1001/jamasurg.2015.4263 PG 9 WC Surgery SC Surgery GA DJ7SE UT WOS:000374411000004 PM 26606675 ER PT J AU Waltz, PK Zuckerbraun, BS AF Waltz, Paul K. Zuckerbraun, Brian S. TI The High Stakes of Postoperative Clostridium difficile Infection SO JAMA SURGERY LA English DT Editorial Material C1 [Waltz, Paul K.; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Waltz, Paul K.; Zuckerbraun, Brian S.] Univ Pittsburgh, 200 Lothrop St,F1200 PUH, Pittsburgh, PA 15213 USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, 200 Lothrop St,F1200 PUH, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD APR PY 2016 VL 151 IS 4 BP 322 EP 322 DI 10.1001/jamasurg.2015.4254 PG 1 WC Surgery SC Surgery GA DJ7SE UT WOS:000374411000005 PM 26606279 ER PT J AU Shapiro, M Chen, Q Huang, Q Boosalis, VA Yoon, CH Saund, MS Whang, EE Gold, JS AF Shapiro, Mia Chen, Qi Huang, Qin Boosalis, Valia A. Yoon, Charles H. Saund, Mandeep S. Whang, Edward E. Gold, Jason S. TI Associations of Socioeconomic Variables With Resection, Stage, and Survival in Patients With Early-Stage Pancreatic Cancer SO JAMA SURGERY LA English DT Article ID RACIAL DISPARITIES; UNITED-STATES; SURGERY; IMPACT; CARE AB IMPORTANCE Socioeconomic variables including sex, race, ethnicity, marital status, and insurance status are associated with survival in pancreatic cancer. It remains unknown exactly how these variables influence survival, including whether they affect stage at presentation or receipt of treatment or are independently associated with outcomes. OBJECTIVES To investigate the relationship between socioeconomic factors and odds of resection in early-stage, resectable pancreatic adenocarcinoma and to determine whether these same factors were independently associated with survival in patients who underwent resection. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective cohort study of patients diagnosed as having T1 through T3 M0 pancreatic adenocarcinoma between January 1, 2004, and December 31, 2011, identified from the Surveillance, Epidemiology, and End Results database. MAIN OUTCOMES AND MEASURES Socioeconomic and geographic variables associated with utilization of resection and disease-specific survival. RESULTS A total of 17 530 patients with localized, nonmetastatic pancreatic cancer were identified. The resection rate among these patients was 45.4% and did not change over time. Utilization of resection was independently associated with white vs African American race (odds ratio [OR]=0.76; 95% CI, 0.65-0.88; P<.001), non-Hispanic ethnicity (for Hispanic, OR=0.72; 95% CI, 0.60-0.85; P<.001), married status (OR=1.42; 95% CI, 1.30-1.57; P<.001), insurance coverage (OR=1.63; 95% CI, 1.22-2.18; P=.001), and the Northeast region (vs Southeast, OR=1.67; 95% CI, 1.44-1.94; P<.001). Stage at presentation correlated with sex, race, ethnicity, marital status, and geographic region (ethnicity, P=.003; all others, P<.001); however, the factors associated with increased resection correlated with more advanced stage. Patients who underwent resection had significantly improved disease-specific survival compared with those who did not undergo resection (median, 21 vs 6 months; hazard ratio [HR] for disease-specific death=0.32; 95% CI, 0.31-0.33; P<.001). Disease-specific survival among the patients who underwent surgical resection was independently associated with geographic region, with patients in the Pacific West (HR for death=0.706; 95% CI, 0.628-0.793), Northeast (HR for death=0.766; 95% CI, 0.667-0.879), and Midwest (HR for death=0.765; 95% CI, 0.640-0.913) having improved survival in comparison with those in the Southeast (all P<.001). CONCLUSIONS AND RELEVANCE Disparities in the utilization of surgical resection for patients with early-stage, resectable pancreatic cancer are associated with socioeconomic variables including race, ethnicity, marital status, insurance status, and geographic location. Of these factors, only geographic location is independently associated with survival in patients undergoing resection. C1 [Shapiro, Mia; Huang, Qin; Yoon, Charles H.; Saund, Mandeep S.; Whang, Edward E.; Gold, Jason S.] Harvard Univ, Sch Med, Boston, MA USA. [Shapiro, Mia; Whang, Edward E.; Gold, Jason S.] VA Boston Healthcare Syst, Surg Serv, Boston, MA USA. [Chen, Qi] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Chen, Qi; Boosalis, Valia A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Huang, Qin] VA Boston Healthcare Syst, Pathol Serv, Boston, MA USA. [Boosalis, Valia A.] VA Boston Healthcare Syst, Med Serv, Boston, MA USA. [Yoon, Charles H.; Whang, Edward E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Saund, Mandeep S.] Harvard Vanguard Med Associates, Boston, MA USA. [Saund, Mandeep S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Gold, JS (reprint author), VA Boston Healthcare Syst 112, Surg Serv, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM jgold4@partners.org NR 18 TC 3 Z9 3 U1 4 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD APR PY 2016 VL 151 IS 4 BP 338 EP 345 DI 10.1001/jamasurg.2015.4239 PG 8 WC Surgery SC Surgery GA DJ7SE UT WOS:000374411000009 PM 26581025 ER PT J AU Roland, CL Boland, GM Demicco, EG Lusby, K Ingram, D May, CD Kivlin, CM Watson, K Al Sannaa, GA Wang, WL Ravi, V Pollock, RE Lev, D Cormier, JN Hunt, KK Feig, BW Lazar, AJ Torres, KE AF Roland, Christina L. Boland, Genevieve M. Demicco, Elizabeth G. Lusby, Kristelle Ingram, Davis May, Caitlin D. Kivlin, Christine M. Watson, Kelsey Al Sannaa, Ghadah A. Wang, Wei-Lien Ravi, Vinod Pollock, Raphael E. Lev, Dina Cormier, Janice N. Hunt, Kelly K. Feig, Barry W. Lazar, Alexander J. Torres, Keila E. TI Clinical Observations and Molecular Variables of Primary Vascular Leiomyosarcoma SO JAMA SURGERY LA English DT Article ID INFERIOR VENA-CAVA; SOFT-TISSUE SARCOMA; FACTOR-RECEPTOR IGF-1R; BETA-CATENIN; ADJUVANT CHEMOTHERAPY; EUROPEAN ORGANIZATION; SURGICAL-MANAGEMENT; MONOCLONAL-ANTIBODY; SOLID TUMORS; CANCER AB IMPORTANCE Vascular leiomyosarcomas are a rare subtype of leiomyosarcomas that most commonly affect the inferior vena cava and account for 5% of all leiomyosarcomas. These tumors are aggressive malignant tumors for which adjuvant modalities have not shown increased efficacy compared with surgery. OBJECTIVES To evaluate the outcomes of patients with vascular leiomyosarcoma and the association between vascular leiomyosarcomas and immunohistochemical molecular markers, to determine their potential prognostic and therapeutic utility. DESIGN, SETTING, AND PARTICIPANTS Retrospective medical record review of a cohort of 77 patients who presented to the University of Texas MD Anderson Cancer Center in Houston during the period from January 1993 to April 2012. Data were analyzed during the period from November 2012 to May 2015. All of the patients received a confirmed diagnosis of vascular leiomyosarcoma. Immunohistochemical studies for biomarkers were performed on a tissue microarray that included 26 primary specimens of vascular leiomyosarcoma. MAIN OUTCOMES AND MEASURES Demographic and clinical factors were evaluated to assess clinical course, patterns of recurrence, and survival outcomes for patients with primary vascular leiomyosarcoma. A univariate Cox proportional hazards model was used to correlate disease-specific survival and time to recurrence with potential prognostic indicators. RESULTS Sixty-three patients with localized disease who underwent surgical resection formed the study population, and their data were used for subsequent outcomes analysis. The median age at diagnosis was 58 years (range, 22-78 years). The majority of patients were female (41 patients [65%]) and white (51 patients [81%]). The 5-year disease-specific survival rate after tumor resection was 65%. The median time to local recurrence was 43 months, the median time to distant recurrence was 25 months, and the median time to concurrent local and distant recurrences was 15 months (P=.04). Strong expressions of cytoplasmic beta-catenin (hazard ratio, 5.33 [95% CI, 0.97-29.30]; P=.06) and insulinlike growth factor 1 receptor (hazard ratio, 2.74 [95% CI, 1.14-6.56]; P=.02) were associated with inferior disease-specific survival. CONCLUSIONS AND RELEVANCE Vascular leiomyosarcomas are aggressive malignant tumors, with high recurrence rates. Expressions of beta-catenin and insulinlike growth factor 1 receptor were associated with poor disease-specific survival. Prospective studies should evaluate the clinical and therapeutic utility of these molecular markers. C1 [Roland, Christina L.; Boland, Genevieve M.; Watson, Kelsey; Cormier, Janice N.; Hunt, Kelly K.; Feig, Barry W.; Torres, Keila E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, 1400 Pressler St,Unit 1484, Houston, TX 77030 USA. [Boland, Genevieve M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Demicco, Elizabeth G.; Al Sannaa, Ghadah A.; Wang, Wei-Lien; Lazar, Alexander J.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Demicco, Elizabeth G.] Mt Sinai Hosp, Dept Pathol, New York, NY 10029 USA. [Lusby, Kristelle; Ingram, Davis; May, Caitlin D.; Kivlin, Christine M.; Lev, Dina] Univ Texas MD Anderson Canc Ctr, Sarcoma Res Ctr, Houston, TX 77030 USA. [May, Caitlin D.; Kivlin, Christine M.] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA. [Ravi, Vinod] Univ Texas MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. [Pollock, Raphael E.] Ohio State Univ, Dept Surg, Columbus, OH 43210 USA. [Lev, Dina] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. RP Torres, KE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, 1400 Pressler St,Unit 1484, Houston, TX 77030 USA. EM ketorres@mdanderson.org RI Lazar, Alexander/A-3416-2008 OI Lazar, Alexander/0000-0002-6395-4499 FU National Institutes of Health; National Cancer Institute [K08CA160443, P30CA016672]; Sally M. Kingsbury Sarcoma Research Foundation; Marty Lindley Foundation; Amschwand Foundation FX Funding for this research was provided in part by the National Institutes of Health and the National Cancer Institute (grant K08CA160443 to Dr Torres and Cancer Center Support grant P30CA016672 to Dr Boland), the Sally M. Kingsbury Sarcoma Research Foundation (Dr Torres), the Marty Lindley Foundation (Dr Torres), and the Amschwand Foundation (Dr May). NR 34 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD APR PY 2016 VL 151 IS 4 BP 347 EP 354 DI 10.1001/jamasurg.2015.4205 PG 8 WC Surgery SC Surgery GA DJ7SE UT WOS:000374411000011 PM 26629783 ER PT J AU Yao, K Belkora, J Sisco, M Rosenberg, S Bedrosian, I Liederbach, E Wang, C AF Yao, Katharine Belkora, Jeff Sisco, Mark Rosenberg, Shoshana Bedrosian, Isabelle Liederbach, Erik Wang, Chihsiung TI Survey of the Deficits in Surgeons' Knowledge of Contralateral Prophylactic Mastectomy SO JAMA SURGERY LA English DT Letter ID BREAST-CANCER; PERCEPTIONS C1 [Yao, Katharine; Sisco, Mark; Liederbach, Erik] NorthShore Univ HealthSyst, Dept Surg, Evanston Hosp, 2650 Ridge Ave,Walgreen Bldg,Ste 2507, Evanston, IL 60201 USA. [Belkora, Jeff] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Rosenberg, Shoshana] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bedrosian, Isabelle] Univ Texas MD Anderson Canc Ctr, Dept Surg, Houston, TX 77030 USA. [Wang, Chihsiung] NorthShore Univ HealthSyst, Ctr Biomed Res Informat, Evanston, IL 60201 USA. RP Yao, K (reprint author), NorthShore Univ HealthSyst, Dept Surg, Evanston Hosp, 2650 Ridge Ave,Walgreen Bldg,Ste 2507, Evanston, IL 60201 USA. EM kyao@northshore.org NR 6 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD APR PY 2016 VL 151 IS 4 BP 391 EP 393 DI 10.1001/jamasurg.2015.3601 PG 4 WC Surgery SC Surgery GA DJ7SE UT WOS:000374411000023 PM 26606424 ER PT J AU Inamura, K Song, MY Jung, S Nishihara, R Yamauchi, M Lochhead, P Qian, ZR Kim, SA Mima, K Sukawa, Y Masuda, A Imamura, Y Zhang, XH Pollak, MN Mantzoros, CS Harris, CC Giovannucci, E Fuchs, CS Cho, E Chan, AT Wu, KN Ogino, S AF Inamura, Kentaro Song, Mingyang Jung, Seungyoun Nishihara, Reiko Yamauchi, Mai Lochhead, Paul Qian, Zhi Rong Kim, Sun A. Mima, Kosuke Sukawa, Yasutaka Masuda, Atsuhiro Imamura, Yu Zhang, Xuehong Pollak, Michael N. Mantzoros, Christos S. Harris, Curtis C. Giovannucci, Edward Fuchs, Charles S. Cho, Eunyoung Chan, Andrew T. Wu, Kana Ogino, Shuji TI Prediagnosis Plasma Adiponectin in Relation to Colorectal Cancer Risk According to KRAS Mutation Status SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; LIFE-STYLE FACTORS; KI-RAS MUTATIONS; PIK3CA MUTATION; WEIGHT ADIPONECTIN; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; PROGNOSTIC ROLE; ASSOCIATIONS; PREVENTION AB Background: Low levels of adiponectin (ADIPOQ; HGNC ID; HGNC: 13633), an adipokine, are associated with obesity, adiposity, excess energy balance, and increased risk of colorectal neoplasia. Given the reported association of increased body mass index (BMI) and low-level physical activity with KRAS-mutated colorectal tumor, we hypothesized that low-level plasma adiponectin might be associated with increased risk of KRAS-mutant colorectal carcinoma but not with risk of KRAS wild-type carcinoma. Methods: We conducted molecular pathological epidemiology research using a nested case-control study design (307 incident rectal and colon cancer case patients and 593 matched control individuals) within prospective cohort studies, the Nurses' Health Study (152 case patients and 297 control individuals, with blood collection in 1989-1990) and the Health Professionals Follow-up Study (155 case patients and 296 control individuals, with blood collection in 1993-1995). Multivariable conditional logistic regression models and two-sided likelihood ratio tests were used to assess etiologic heterogeneity of the associations. Results: The association of low-level plasma adiponectin with colorectal cancer risk statistically significantly differed by KRAS mutation status (P-heterogeneity = .004). Low levels of plasma adiponectin were associated with KRAS-mutant colorectal cancer (for the lowest vs highest tertile: multivariable odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.50 to 5.34, P-trend = .002) but not with KRAS wild-type cancer (for the lowest vs highest tertile: multivariable OR = 0.83, 95% CI = 0.49 to 1.43, P-trend = .48). In secondary analyses, the association between plasma adiponectin and colorectal cancer did not appreciably differ by BRAF or PIK3CA oncogene mutation status. Conclusions: Low-level plasma adiponectin is associated with KRAS-mutant colorectal cancer risk but not with KRAS wildtype cancer risk. C1 [Inamura, Kentaro; Nishihara, Reiko; Yamauchi, Mai; Lochhead, Paul; Qian, Zhi Rong; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Imamura, Yu; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Inamura, Kentaro; Nishihara, Reiko; Yamauchi, Mai; Lochhead, Paul; Qian, Zhi Rong; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Imamura, Yu; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Inamura, Kentaro; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. [Inamura, Kentaro] Japanese Fdn Canc Res, Inst Canc, Div Pathol, Tokyo 170, Japan. [Song, Mingyang; Nishihara, Reiko; Giovannucci, Edward; Wu, Kana] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave,Bldg 2,Room 302, Boston, MA 02115 USA. [Song, Mingyang; Giovannucci, Edward; Ogino, Shuji] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Nishihara, Reiko] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Jung, Seungyoun; Zhang, Xuehong; Giovannucci, Edward; Fuchs, Charles S.; Cho, Eunyoung; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Lochhead, Paul; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Pollak, Michael N.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA USA. [Cho, Eunyoung] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI USA. RP Wu, KN (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave,Bldg 2,Room 302, Boston, MA 02115 USA.; Ogino, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Room M422, Boston, MA 02215 USA. EM kana.wu@channing.harvard.edu; shuji_ogino@dfci.harvard.edu FU National Institutes of Health (NIH) [P01 CA87969, P01 CA55075, UM1 CA167552, UM1 CA186107, P50 CA127003, R01 CA136950, R01 CA137178, K24 DK098311, R01 CA151993, R35 CA197735, K07 CA190673]; Paula and Russell Agrusa Fund for Colorectal Cancer Research; Friends of the Dana-Farber Cancer Institute; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Japan Society for the Promotion of Science; Takashi Tsuruo Memorial Fund; Harvard University Frank Knox Memorial Fellowship; Asan Medical Center; Uehara Memorial Foundation FX This work was supported by National Institutes of Health (NIH) grants (P01 CA87969 to SEH; P01 CA55075 to WCW; UM1 CA167552 to WCW; UM1 CA186107 to MJS; P50 CA127003 to CSF; R01 CA136950 to EC; R01 CA137178 and K24 DK098311 to ATC; R01 CA151993 and R35 CA197735 to SO; and K07 CA190673 to RN) and by grants from the Paula and Russell Agrusa Fund for Colorectal Cancer Research (to CSF), the Friends of the Dana-Farber Cancer Institute (to SO), and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. KI was supported by a Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad and by Takashi Tsuruo Memorial Fund. MS is a trainee of the Harvard Transdisciplinary Research Center on Energetics and Cancer (TREC). PL is a Scottish Government Clinical Academic Fellow and was supported by a Harvard University Frank Knox Memorial Fellowship. SAK was supported by an early exchange postdoctoral fellowship grant from Asan Medical Center. KM is supported by a fellowship grant from the Uehara Memorial Foundation. ATC is a Damon Runyon Clinical Investigator. NR 63 TC 1 Z9 1 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2016 VL 108 IS 4 AR djv363 DI 10.1093/jnci/djv363 PG 10 WC Oncology SC Oncology GA DK6RR UT WOS:000375053400025 ER PT J AU Playdon, MC Bracken, MB Sanft, TB Ligibel, JA Harrigan, M Irwin, ML AF Playdon, Mary C. Bracken, Michael B. Sanft, Tara B. Ligibel, Jennifer A. Harrigan, Maura Irwin, Melinda L. TI RE: Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic Review and Meta-Analysis RESPONSE SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID SURVIVAL; WOMEN C1 [Playdon, Mary C.; Bracken, Michael B.; Harrigan, Maura; Irwin, Melinda L.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06520 USA. [Sanft, Tara B.; Irwin, Melinda L.] Yale Univ, Ctr Canc, New Haven, CT 06520 USA. [Ligibel, Jennifer A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Playdon, MC (reprint author), Yale Univ, 60 Coll St, New Haven, CT 06520 USA. EM mary.playdon@yale.edu RI Playdon, Mary/I-4050-2016 NR 7 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2016 VL 108 IS 4 AR djw024 DI 10.1093/jnci/djw024 PG 2 WC Oncology SC Oncology GA DK6RR UT WOS:000375053400005 ER PT J AU Raymond, VM Gray, SW Roychowdhury, S Joffe, S Chinnaiyan, AM Parsons, DW Plon, SE AF Raymond, Victoria M. Gray, Stacy W. Roychowdhury, Sameek Joffe, Steve Chinnaiyan, Arul M. Parsons, D. Williams Plon, Sharon E. CA Clinical Sequencing Exploratory TI Germline Findings in Tumor-Only Sequencing: Points to Consider for Clinicians and Laboratories SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GENOME; CANCER; MUTATIONS; EXOME; RECOMMENDATIONS; ASSOCIATION; FRAMEWORK; BREAST AB Precision oncology holds great potential to improve patient therapies and outcomes. Tumor sequencing is rapidly moving into clinical care as our understanding of the cancer genome and the availability of targeted therapies increase. Analysis of the cancer genome is most informative when paired with germline genomic DNA to delineate inherited and somatic variants. Although tumor-only analysis remains the most common methodology for numerous reasons, it holds the potential to identify clinically significant germline variants. Here, we provide anticipatory guidance and points to consider for laboratories and clinicians regarding the potential for germline findings in tumor sequencing. C1 [Raymond, Victoria M.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Chinnaiyan, Arul M.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Gray, Stacy W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gray, Stacy W.] Harvard Univ, Sch Med, Boston, MA USA. [Roychowdhury, Sameek] Ohio State Univ, Columbus, OH 43210 USA. [Joffe, Steve] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Parsons, D. Williams; Plon, Sharon E.] Texas Childrens Canc Ctr, Houston, TX USA. [Parsons, D. Williams; Plon, Sharon E.] Baylor Coll Med, Houston, TX 77030 USA. RP Raymond, VM (reprint author), Univ Michigan, 5309 CCC 5940,400 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM vraymond@umich.edu NR 27 TC 6 Z9 6 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2016 VL 108 IS 4 AR djv351 DI 10.1093/jnci/djv351 PG 5 WC Oncology SC Oncology GA DK6RR UT WOS:000375053400019 ER PT J AU Lo, EH Ning, MM AF Lo, Eng H. Ning, MingMing TI Mechanisms and challenges in translational stroke research SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article ID NERVOUS-SYSTEM; NEUROVASCULAR UNIT; CELL-DEATH; BRAIN; HEART; DISEASE; INJURY; REPAIR; ANGIOGENESIS; ASSOCIATION AB Translating basic science advances into clinical meaning has been challenging for stroke research. This does not, however, mean that the investigation of basic mechanisms is irrelevant. Translation is difficult because the underlying mechanisms are complex and ill-defined. The original focus on neuroprotection has now evolved into a broader consideration of the role of non-neuronal cells in stroke pathophysiology. The neurovascular unit may provide a conceptual framework within which interactions between neural, glial, and vascular cells comprise a basis for function and dysfunction in the central nervous system. Importantly, these cell-cell signaling pathways are also biphasic in nature, that is, mechanisms that are deleterious in the acute phase may surprisingly be required for neurovascular remodeling and plasticity during stroke recovery. Furthermore, injury-into-repair gradients are significantly influenced by a host of modifying factors and comorbidities. Rigorous dissection of these complex and recursive mechanisms should be required before they can be rationally targeted for stroke. C1 [Lo, Eng H.; Ning, MingMing] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Boston, MA 02129 USA. EM Lo@helix.mgh.harvard.edu NR 33 TC 3 Z9 3 U1 1 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2016 VL 64 IS 4 BP 827 EP 829 DI 10.1136/jim-2016-000104 PG 3 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DK3CI UT WOS:000374792900001 PM 26962212 ER PT J AU Lamming, DW Cummings, NE Apelo, SA Neuman, JC Schmidt, B Merrins, M Kimple, M Fontana, L AF Lamming, D. W. Cummings, N. E. Apelo, S. Arriola Neuman, J. C. Schmidt, B. Merrins, M. Kimple, M. Fontana, L. TI IMPROVING GLYCEMIC CONTROL THROUGH REDUCTION OF SPECIFIC DIETARY AMINO ACIDS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Midwestern Regional Meeting of the American-Federation-for-Medical-Research (AFMR) CY APR 21, 2016 CL Chicago, IL SP Amer Federat Med Res C1 [Lamming, D. W.; Cummings, N. E.; Apelo, S. Arriola; Neuman, J. C.; Schmidt, B.; Merrins, M.; Kimple, M.] Univ Wisconsin, Med, Madison, WI USA. [Lamming, D. W.; Cummings, N. E.; Apelo, S. Arriola; Neuman, J. C.; Schmidt, B.; Merrins, M.; Kimple, M.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Fontana, L.] Washington Univ, Geriatr & Nutr Sci, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2016 VL 64 IS 4 MA 78 BP 926 EP 926 DI 10.1136/jim-2016-000120.32 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DK3CI UT WOS:000374792900047 ER PT J AU Suryadevara, V Royston, T Berdyshev, E Huang, L Natarajan, V Tager, A AF Suryadevara, V. Royston, T. Berdyshev, E. Huang, L. Natarajan, V. Tager, A. TI ROLE OF PHOSPHOLIPASE D IN IDIOPATHIC PULMONARY FIBROSIS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Midwestern Regional Meeting of the American-Federation-for-Medical-Research (AFMR) CY APR 21, 2016 CL Chicago, IL SP Amer Federat Med Res C1 [Suryadevara, V.; Royston, T.] Univ Illinois, Bioengn, Chicago, IL USA. [Berdyshev, E.] Natl Jewish Hlth, Denver, CO USA. [Huang, L.; Natarajan, V.] Univ Illinois, Pharmacol, Chicago, IL USA. [Tager, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2016 VL 64 IS 4 MA 112 BP 964 EP 964 DI 10.1136/jim-2016-000120.108 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DK3CI UT WOS:000374792900119 ER PT J AU Apelo, SA Pumper, CP Baar, EL Cummings, NE Brar, HK Kimple, ME Lamming, DW Neuman, JC AF Apelo, S. Arriola Pumper, C. P. Baar, E. L. Cummings, N. E. Brar, H. K. Kimple, M. E. Lamming, D. W. Neuman, J. C. TI ALTERNATIVE RAPAMYCIN TREATMENT REGIMENS MITIGATE THE IMPACT OF RAPAMYCIN ON GLUCOSE HOMEOSTASIS AND THE IMMUNE SYSTEM, AND EXTENDS LIFESPAN SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Midwestern Regional Meeting of the American-Federation-for-Medical-Research (AFMR) CY APR 21, 2016 CL Chicago, IL SP Amer Federat Med Res C1 [Apelo, S. Arriola; Pumper, C. P.; Baar, E. L.; Cummings, N. E.; Brar, H. K.; Kimple, M. E.; Lamming, D. W.] Univ Wisconsin, Div Endocrinol Diabet & Metab, Med, Madison, WI USA. [Neuman, J. C.] Univ Wisconsin, Interdisciplinary Grad Program Nutr Sci, Madison, WI USA. [Apelo, S. Arriola; Pumper, C. P.; Baar, E. L.; Cummings, N. E.; Brar, H. K.; Kimple, M. E.; Lamming, D. W.; Neuman, J. C.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2016 VL 64 IS 4 MA 21 DI 10.1136/jim-2016-000120.45 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DK3CI UT WOS:000374792900060 ER PT J AU Fisichella, PM AF Fisichella, P. Marco TI The New Era of Journal of Laparoendoscopic & Advanced Surgical Techniques SO JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES LA English DT Editorial Material C1 [Fisichella, P. Marco] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston VA Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. RP Fisichella, PM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston VA Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM piero.fisichella@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1092-6429 EI 1557-9034 J9 J LAPAROENDOSC ADV S JI J. Laparoendosc. Adv. Surg. Tech. PD APR PY 2016 VL 26 IS 4 BP 239 EP 239 DI 10.1089/lap.2016.29006.pmf PG 1 WC Surgery SC Surgery GA DK3SR UT WOS:000374838200001 PM 27096815 ER PT J AU Tobler, WD Itani, KMF AF Tobler, William D., Jr. Itani, Kamal M. F. TI Current Status and Challenges of Laparoscopy in Ventral Hernia Repair SO JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ABDOMINAL-WALL RECONSTRUCTION; LARGE INCISIONAL HERNIA; QUALITY-OF-LIFE; OBESE-PATIENTS; MESH REPAIR; FIXATION TECHNIQUE; TERM OUTCOMES; OPEN SURGERY; HERNIORRHAPHY AB Laparoscopic repair of ventral hernias gained strong popularity in the late nineties with some of the early enthusiasm lost later in time. We review the current status and challenges of laparoscopy in ventral hernia repair and best practices in this area. We specifically looked at patient and hernia defect factors, technical considerations that have contributed to the successes, and some of the failures of laparoscopic ventral hernia repair (LVHR). Patients best suited for a laparoscopic repair are those who are obese and diabetic with a total defect size not to exceed 10cm in width or a Swiss cheese defect. Overlap of mesh to healthy fascia of at least 5cm in every direction, with closure of the defect, is essential to prevent recurrence or bulging over time. Complications specifically related to surgical site occurrence favor the laparoscopic approach. Recurrence rates, satisfaction, and health-related quality of life results are similar to open repairs, but long-term data are lacking. There is still conflicting data regarding ways of fixating the mesh. The science of prosthetic material appropriate for intraperitoneal placement continues to evolve. The field continues to be plagued by single author, single institution, and small nonrandomized observational studies with short-term follow-up. The recent development of large prospective databases might allow for pragmatic and point-of-care studies with long-term follow-up. We conclude that LVHR has evolved since its inception, has overcome many challenges, but still needs better long-term studies to evaluate evolving practices. C1 [Tobler, William D., Jr.] Univ Pittsburgh, Dept Plast Surg, Pittsburgh, PA USA. [Itani, Kamal M. F.] Boston Univ, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Itani, KMF (reprint author), VA Boston Healthcare Syst, Dept Surg, West Roxbury, MA 02132 USA. EM kitani@med.va.gov NR 94 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1092-6429 EI 1557-9034 J9 J LAPAROENDOSC ADV S JI J. Laparoendosc. Adv. Surg. Tech. PD APR PY 2016 VL 26 IS 4 BP 281 EP 289 DI 10.1089/lap.2016.0095 PG 9 WC Surgery SC Surgery GA DK3SR UT WOS:000374838200009 PM 27027828 ER PT J AU Graves, MC Harris, JR Kohn, M Hannon, PA Lichiello, PA Martin, DP Ahmed, F AF Graves, Meredith C. Harris, Jeffrey R. Kohn, Marlana Hannon, Peggy A. Lichiello, Patricia A. Martin, Diane P. Ahmed, Faruque TI Employers' Views on Influenza and Tetanus-Diphtheria-Pertussis Vaccination in the Workplace SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Letter ID UNITED-STATES; ADULTS; COSTS C1 [Harris, Jeffrey R.; Kohn, Marlana; Hannon, Peggy A.; Lichiello, Patricia A.; Martin, Diane P.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Harris, Jeffrey R.; Kohn, Marlana; Hannon, Peggy A.] Univ Washington, Hlth Promot Res Ctr, Ctr Dis Control & Prevent, Res Ctr, Seattle, WA 98195 USA. [Graves, Meredith C.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Ahmed, Faruque] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. RP Graves, MC (reprint author), VA Puget Sound Healthcare Syst, Seattle, WA USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD APR PY 2016 VL 58 IS 4 BP E157 EP E158 DI 10.1097/JOM.0000000000000693 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DK4ME UT WOS:000374891600009 PM 27058495 ER PT J AU Fuentes, E Ahmad, R Hong, TS Clark, JW Kwak, EL Rattner, DW Mullen, JT AF Fuentes, Eva Ahmad, Rima Hong, Theodore S. Clark, Jeffrey W. Kwak, Eunice L. Rattner, David W. Mullen, John T. TI The Impact of Neoadjuvant Therapy for Gastroesophageal Adenocarcinoma on Postoperative Morbidity and Mortality SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE gastric cancer; neoadjuvant therapy; postoperative morbidity; mortality; outcomes ID PREOPERATIVE CHEMORADIOTHERAPY; GASTRIC-CANCER; PERIOPERATIVE CHEMOTHERAPY; TOTAL GASTRECTOMY; SURGERY; TRIAL; CLASSIFICATION; COMPLICATIONS; STOMACH AB Background and Objectives: We sought to study the impact of neoadjuvant therapy (NAT) on postoperative complications following surgical resection of adenocarcinomas of the stomach and gastroesophageal junction (GEJ). Methods: We compared the postoperative outcomes of 308 patients undergoing a surgery-first approach and 145 patients undergoing NAT followed by curative-intent surgery for adenocarcinomas of the stomach and GEJ from 1995-2014. Results: Patients receiving NAT were more likely to be younger, have tumors of the GEJ, to undergo esophagogastrectomy and D2 lymphadenectomy, and to have more advanced stage disease than patients undergoing surgery first. There were no differences in overall 30-day morbidity or mortality rates between the groups, yet patients undergoing surgery first were more likely to have higher-grade complications than those undergoing NAT. Age >65 years, higher ASA score, concomitant splenectomy, more advanced tumor stage, and year of surgery were independent risk factors for postoperative morbidity, but receipt of NAT was not an independent predictor of postoperative morbidity. Conclusions: Despite having more advanced disease and undergoing higher-risk surgical procedures, patients with adenocarcinomas of the stomach or GEJ who receive NAT prior to surgery are no more likely to suffer postoperative complications than patients treated with a surgery-first approach. (C) 2016 Wiley Periodicals, Inc. C1 [Fuentes, Eva; Ahmad, Rima; Rattner, David W.; Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. [Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Clark, Jeffrey W.; Kwak, Eunice L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM jmullen@partners.org NR 18 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD APR 1 PY 2016 VL 113 IS 5 BP 560 EP 564 DI 10.1002/jso.24179 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA DK7PT UT WOS:000375118900016 PM 26792144 ER PT J AU Wang, HT Jacobson, A Harmon, DC Choy, E Hornicek, FJ Raskin, KA Chebib, IA DeLaney, TF Chen, YLE AF Wang, Haotong Jacobson, Alex Harmon, David C. Choy, Edwin Hornicek, Francis J. Raskin, Kevin A. Chebib, Ivan A. DeLaney, Thomas F. Chen, Yen-Lin E. TI Prognostic Factors in Alveolar Soft Part Sarcoma: A SEER Analysis SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE ASPS; soft tissue sarcoma; survival; surgical treatment ID ADOLESCENTS; CHILDREN; 17Q25; GENE AB Objectives: We reviewed the clinical characteristics and outcomes of patients treated for alveolar soft part sarcoma (ASPS) and analyzed the effect of surgery for patients presenting with and without metastatic disease (DM). Methods: The SEER Registry was queried for patients with ASPS from 1973-2012. The Kaplan-Meier estimate and Cox proportional hazards were used to analyze survival outcomes and risk variables. Results: Among 251 patients, 43% had DM and 67% locoregional disease (LR) on presentation. The 5-year overall survival (OS) for all patients was 56% (82% and 27% for LR and DM, respectively). Multivariate analysis identified older age (hazard ratio [HR] = 1.03 per year, P < 0.001), tumor size >10cm (HR = 2.76, P = 0.013), DM at diagnosis (HR = 3.79, P < 0.001), and truncal primary site (HR = 1.63, P = 0.035) as independent factors predicting worse OS. For LR patients, surgery plus radiotherapy (RT) resulted in better OS compared to surgery alone P = 0.014. For DM patients, primary site surgery significantly improved survival (P < 0.001). Conclusion: ASPS presents with high metastasis rate but has a relatively indolent clinical course and a favorable prognosis with prolonged survival. Aggressive treatment using adjuvant RT with surgery is indicated in patients with LR disease and surgery is indicated in patients presenting with DM. (C) 2016 Wiley Periodicals, Inc. C1 [Wang, Haotong; Jacobson, Alex; DeLaney, Thomas F.; Chen, Yen-Lin E.] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr 55 Fruit St, Boston, MA 02114 USA. [Harmon, David C.; Choy, Edwin] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Harmon, David C.; Choy, Edwin; Hornicek, Francis J.; Raskin, Kevin A.; Chebib, Ivan A.; DeLaney, Thomas F.; Chen, Yen-Lin E.] Harvard Univ, Sch Med, Boston, MA USA. [Hornicek, Francis J.; Raskin, Kevin A.] Massachusetts Gen Hosp, Dept Orthoped Oncol, Boston, MA 02114 USA. [Chebib, Ivan A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Chen, YLE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr 55 Fruit St, Boston, MA 02114 USA. EM ychen9@mgh.harvard.edu NR 21 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD APR 1 PY 2016 VL 113 IS 5 BP 581 EP 586 DI 10.1002/jso.24183 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA DK7PT UT WOS:000375118900020 PM 26804150 ER PT J AU Plasek, JM Goss, FR Lai, KH Lau, JJ Seger, DL Blumenthal, KG Wickner, PG Slight, SP Chang, FY Topaz, M Bates, DW Zhou, L AF Plasek, Joseph M. Goss, Foster R. Lai, Kenneth H. Lau, Jason J. Seger, Diane L. Blumenthal, Kimberly G. Wickner, Paige G. Slight, Sarah P. Chang, Frank Y. Topaz, Maxim Bates, David W. Zhou, Li TI Food entries in a large allergy data repository SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article DE food hypersensitivity; natural language processing; allergy and immunology; electronic health records; systematized nomenclature of medicine; vocabulary; controlled ID UNITED-STATES; PREVALENCE; DRUG; FEATURES; CHILDREN; PEANUT AB Methods Using the Medical Text Extraction, Reasoning, and Mapping System (MTERMS), we processed both structured and free-text entries stored in an enterprise-wide allergy repository (Partners' Enterprise-wide Allergy Repository), normalized diverse food allergen terms into concepts, and encoded these concepts using the Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT) and Unique Ingredient Identifiers (UNII) terminologies. Concept coverage also was assessed for these two terminologies. We further categorized allergen concepts into groups and calculated the frequencies of these concepts by group. Finally, we conducted an external validation of MTERMS's performance when identifying food allergen terms, using a randomized sample from a different institution. Results We identified 158 552 food allergen records (2140 unique terms) in the Partners repository, corresponding to 672 food allergen concepts. High-frequency groups included shellfish (19.3%), fruits or vegetables (18.4%), dairy (9.0%), peanuts (8.5%), tree nuts (8.5%), eggs (6.0%), grains (5.1%), and additives (4.7%). Ambiguous, generic concepts such as "nuts" and "seafood" accounted for 8.8% of the records. SNOMED-CT covered more concepts than UNII in terms of exact (81.7% vs 68.0%) and partial (14.3% vs 9.7%) matches. Discussion Adverse sensitivities to food are diverse, and existing standard terminologies have gaps in their coverage of the breadth of allergy concepts. Conclusion New strategies are needed to represent and standardize food adverse sensitivity concepts, to improve documentation in EHRs. C1 [Plasek, Joseph M.; Lau, Jason J.; Slight, Sarah P.; Topaz, Maxim; Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. [Goss, Foster R.] Tufts Med Ctr, Dept Emergency Med & Clin Decis Making, Boston, MA USA. [Goss, Foster R.] Univ Colorado, Dept Emergency Med, Aurora, CO USA. [Lai, Kenneth H.; Seger, Diane L.] Partners HealthCare Syst, Clin & Qual Anal, Boston, MA USA. [Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Allergy & Immunol, Boston, MA 02114 USA. [Wickner, Paige G.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 75 Francis St, Boston, MA 02115 USA. [Slight, Sarah P.] Univ Durham, Sch Med Pharm & Hlth, Div Pharm, Durham, England. [Chang, Frank Y.; Zhou, Li] Partners HealthCare Syst, Clin Informat, Partners eCare, Boston, MA USA. [Topaz, Maxim; Bates, David W.; Zhou, Li] Harvard Univ, Sch Med, Boston, MA USA. RP Zhou, L (reprint author), Partners HealthCare, 93 Worchester St, Wellesley, MA 02481 USA. EM lzhou2@partners.org FU Agency for HealthCare Research and Quality [1R01HS022728-01] FX This study was funded by Agency for HealthCare Research and Quality grant 1R01HS022728-01. NR 42 TC 0 Z9 0 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD APR PY 2016 VL 23 IS E1 BP E79 EP E87 DI 10.1093/jamia/ocv128 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA DL0AD UT WOS:000375292600011 PM 26384406 ER PT J AU Millegan, J Wang, L LeardMann, CA Miletich, D Street, AE AF Millegan, Jeffrey Wang, Lawrence LeardMann, Cynthia A. Miletich, Derek Street, Amy E. TI Sexual Trauma and Adverse Health and Occupational Outcomes Among Men Serving in the US Military SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID ASSAULT HISTORY; MILLENNIUM COHORT; GENERAL-POPULATION; VETERANS; AFGHANISTAN; INSTRUMENTS; HARASSMENT; WOMEN; PTSD; IRAQ AB Although absolute counts of U.S. service men who experience sexual trauma are comparable to service women, little is known about the impact of sexual trauma on men. The association of recent sexual trauma (last 3 years) with health and occupational outcomes was investigated using longitudinal data (2004-2013) from the Millennium Cohort Study. Of 37,711 service men, 391 (1.0%) reported recent sexual harassment and 76 (0.2%) sexual assault. In multivariable models, sexual harassment or assault, respectively, was associated with poorer mental health: AOR = 1.60, 95% CI [1.22, 2.12], AOR = 4.39, 95% CI [2.40, 8.05]; posttraumatic stress disorder: AOR = 2.50, 95% CI [1.87, 3.33], AOR = 6.63, 95% CI [3.65, 12.06]; depression: AOR = 2.37, 95% CI [1.69, 3.33], AOR = 5.60, 95% CI [2.83, 11.09]; and multiple physical symptoms: AOR = 2.22, 95% CI [1.69, 2.92]; AOR = 3.57, 95% CI [1.98, 6.42], after adjustment for relevant covariates. Sexual harassment was also associated with poorer physical health: AOR = 1.68, 95% CI [1.27, 2.22]. Men who reported sexual trauma were more likely to have left military service: AOR = 1.60, 95% CI [1.14, 2.24], and be disabled/unemployed postservice: AOR = 1.76, 95% CI [1.02, 3.02]. Results suggest that sexual trauma was significantly associated with adverse health and functionality extending to postmilitary life. Findings support the need for developing better prevention strategies and services to reduce the burden of sexual trauma on service men. C1 [Millegan, Jeffrey; Miletich, Derek] Naval Med Ctr San Diego, Directorate Mental Hlth, San Diego, CA USA. [Wang, Lawrence; LeardMann, Cynthia A.] Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA USA. [Wang, Lawrence; LeardMann, Cynthia A.] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA. [Street, Amy E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Street, Amy E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP LeardMann, CA (reprint author), Naval Hlth Res Ctr, 140 Sylvester Rd, San Diego, CA 92106 USA. EM cynthia.a.leardmann.ctr@mail.mil FU Department of Defense [60002]; Clinical Investigations Department at Naval Medical Center San Diego; Military Operational Medicine Research Program of the U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland FX The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of the Army, Department of the Air Force, Department of Veterans Affairs, or the U.S. Government. Approved for public release; distribution is unlimited (U.S. Government Work 17 USC 105) and is not copyrighted in the United States. The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. This work is supported by the Department of Defense, under Work Unit No. 60002, and through funding by the Clinical Investigations Department at Naval Medical Center San Diego. The Millennium Cohort Study is funded through the Military Operational Medicine Research Program of the U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland. This research has been conducted in compliance with all applicable federal regulations governing the protection of human subjects in research (Protocol NHRC.2000.0007). In addition to the authors, the Millennium Cohort Study Team includes Richard Armenta, PhD, Lauren Bauer, MPH, Madeline Cross, James Davies, Carrie Donoho, PhD, Dennis Faix, MD, MPH, Susan Farrish, MD, Toni Geronimo, Kathleen Gunn, William Lee, Hector Lemus, PhD, Gordon Lynch, Denise Lovec-Jenkins, David Luxton, PhD, Danielle Mitchell, Kristin Motylinski, Anna Nagel, MPH, Chiping Nieh, PhD, Chris O'Malley, MPH, Serguey Parkhomovsky, Anet Petrosyan, Christopher Phillips, MD, MPH, Teresa Powell, MS, Ben Porter, PhD, Rudy Rull, PhD, Kari Sausedo, MA, Beverly Sheppard, Steven Speigle, Evelyn Sun, MPH, Valerie Stander, PhD, Laura Tobin, MPH, Daniel Trone, PhD, Jennifer Walstrom, from the Deployment Health Research Department, Naval Health Research Center, San Diego, CA. We thank Hector Lemus, PhD (Naval Health Research Center, San Diego, CA) for his contribution in providing statistical support and consultation for this study. In addition, we thank Michelle LeWark from the Naval Health Research Center (San Diego, CA) for her technical review and editing of this paper. The authors also thank the professionals from the U.S. Army Medical Research and Materiel Command, especially those from the Military Operational Medicine Research Program, Fort Detrick, Maryland, and the Millennium Cohort Study participants. NR 29 TC 1 Z9 1 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2016 VL 29 IS 2 BP 132 EP 140 DI 10.1002/jts.22081 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DJ6TZ UT WOS:000374347400004 PM 27077493 ER PT J AU Vargas, RJ Farid, H Goldenson, RP Fairchild, AH Dorton, BJ Bromley, BS AF Vargas, Roberto J. Farid, Huma Goldenson, Robin P. Fairchild, Alexandra H. Dorton, Benjamin J. Bromley, Bryann S. TI Ovarian Teratomas and Anti-N-Methyl-D-Aspartate Receptor Encephalitis: Why Sonography First? SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Letter ID NMDAR ENCEPHALITIS C1 [Vargas, Roberto J.; Farid, Huma; Dorton, Benjamin J.; Bromley, Bryann S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. [Vargas, Roberto J.; Farid, Huma; Dorton, Benjamin J.; Bromley, Bryann S.] Massachusetts Gen Hosp, 75 Francis St, Boston, MA 02114 USA. [Goldenson, Robin P.; Fairchild, Alexandra H.; Bromley, Bryann S.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Vargas, Roberto J.; Farid, Huma; Goldenson, Robin P.; Fairchild, Alexandra H.; Dorton, Benjamin J.; Bromley, Bryann S.] Harvard Univ, Sch Med, Boston, MA USA. RP Vargas, RJ (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR 1 PY 2016 VL 35 IS 4 BP 852 EP 854 DI 10.7863/ultra.15.04064 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA DL0OV UT WOS:000375333200026 PM 27022186 ER PT J AU Wiebe, MS Jamin, A AF Wiebe, Matthew S. Jamin, Augusta TI The Barrier to Autointegration Factor: Interlocking Antiviral Defense with Genome Maintenance SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINIA-RELATED KINASES; HOST-DEFENSE; B1 KINASE; IN-VIVO; DNA; VIRUS; PROTEINS; BAF; COMPLEX; MITOSIS AB Intrinsic defenses targeting foreign DNA are one facet of the cellular armament tasked with protecting host genomic integrity. The DNA binding protein BAF (barrier to autointegration factor) contributes to multiple aspects of genome maintenance and intercepts retrovirus, poxvirus, and herpesvirus genomes during infection. In this gem, we discuss the unique position BAF occupies at the virus-host interface and how both viral and cellular mechanisms may regulate its capacity to act as a pro-or antiviral effector targeting viral DNA. C1 [Wiebe, Matthew S.] Univ Nebraska, Sch Vet Med & Biomed Sci, Lincoln, NE USA. [Wiebe, Matthew S.] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE USA. [Jamin, Augusta] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. RP Wiebe, MS (reprint author), Univ Nebraska, Sch Vet Med & Biomed Sci, Lincoln, NE USA.; Wiebe, MS (reprint author), Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE USA. EM mwiebe@unl.edu FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) [R01AI114653]; HHS \ NIH \ National Institute of General Medical Sciences (NIGMS) [P30GM103509] FX HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) provided funding to Matthew S. Wiebe and Augusta Jamin under grant number R01AI114653. HHS vertical bar NIH vertical bar National Institute of General Medical Sciences (NIGMS) provided funding to Matthew S. Wiebe and Augusta Jamin under grant number P30GM103509. NR 20 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD APR PY 2016 VL 90 IS 8 BP 3806 EP 3809 DI 10.1128/JVI.00178-16 PG 4 WC Virology SC Virology GA DK7RQ UT WOS:000375123800002 PM 26842478 ER PT J AU Tsai, AC Kakuhikire, B Mushavi, R Vorechovska, D Perkins, JM McDonough, AQ Bangsberg, DR AF Tsai, Alexander C. Kakuhikire, Bernard Mushavi, Rumbidzai Vorechovska, Dagmar Perkins, Jessica M. McDonough, Amy Q. Bangsberg, David R. TI Population-based study of intra-household gender differences in water insecurity: reliability and validity of a survey instrument for use in rural Uganda SO JOURNAL OF WATER AND HEALTH LA English DT Article DE gender; Uganda; water insecurity ID FOOD INSECURITY; EMOTIONAL DISTRESS; SOUTH-AFRICA; HUNGER; ACCESS; WOMEN; INDICATORS; COUNTRIES; CHILDREN; DISTANCE AB Hundreds of millions of people worldwide lack adequate access to water. Water insecurity, which is defined as having limited or uncertain availability of safe water or the ability to acquire safe water in socially acceptable ways, is typically overlooked by development organizations focusing on water availability. To address the urgent need in the literature for validated measures of water insecurity, we conducted a population-based study in rural Uganda with 327 reproductive-age women and 204 linked men from the same households. We used a novel method of photo identification so that we could accurately elicit study participants' primary household water sources, thereby enabling us to identify water sources for objective water quality testing and distance/elevation measurement. Our psychometric analyses provided strong evidence of the internal structure, reliability, and validity of a new eight-item Household Water Insecurity Access Scale (HWIAS). Important intra-household gender differences in perceptions of water insecurity were observed, with men generally perceiving household water insecurity as being less severe compared to women. In summary, the HWIAS represents a reliable and valid measure of water insecurity, particularly among women, and may be useful for informing and evaluating interventions to improve water access in resource-limited settings. C1 [Tsai, Alexander C.; Vorechovska, Dagmar; Perkins, Jessica M.; McDonough, Amy Q.; Bangsberg, David R.] Massachusetts Gen Hosp Global Hlth, Boston, MA USA. [Tsai, Alexander C.; Mushavi, Rumbidzai; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Tsai, Alexander C.; Kakuhikire, Bernard; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Perkins, Jessica M.; Bangsberg, David R.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp Global Hlth, Boston, MA USA.; Tsai, AC (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Tsai, AC (reprint author), Mbarara Univ Sci & Technol, Mbarara, Uganda. EM actsai@partners.org FU US National Institutes of Health (NIH) [K23MH096620]; Friends of a Healthy Uganda FX This study was funded by the US National Institutes of Health (NIH) K23MH096620 and Friends of a Healthy Uganda. NR 53 TC 5 Z9 5 U1 2 U2 4 PU IWA PUBLISHING PI LONDON PA ALLIANCE HOUSE, 12 CAXTON ST, LONDON SW1H0QS, ENGLAND SN 1477-8920 J9 J WATER HEALTH JI J. Water Health PD APR PY 2016 VL 14 IS 2 BP 280 EP 292 DI 10.2166/wh.2015.165 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Microbiology; Water Resources SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Microbiology; Water Resources GA DL0OU UT WOS:000375333100012 PM 27105413 ER PT J AU Fajgenbaum, DC Ruth, JR Kelleher, D Rubenstein, AH AF Fajgenbaum, David C. Ruth, Jason R. Kelleher, Dermot Rubenstein, Arthur H. TI The collaborative network approach: a new framework to accelerate Castleman's disease and other rare disease research SO LANCET HAEMATOLOGY LA English DT Editorial Material ID SILTUXIMAB C1 [Fajgenbaum, David C.] Univ Penn, Dept Med, Perelman Sch Med, Div Hematol Oncol,Orphan Dis Ctr, Philadelphia, PA 19104 USA. [Fajgenbaum, David C.] Univ Penn, Leonard Davis Inst Hlth Econ, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Rubenstein, Arthur H.] Univ Penn, Dept Med, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Ruth, Jason R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Kelleher, Dermot] Univ British Columbia, Fac Med, Vancouver, BC V6T 1Z1, Canada. RP Fajgenbaum, DC (reprint author), Univ Penn, Dept Med, Perelman Sch Med, Div Hematol Oncol,Orphan Dis Ctr, Philadelphia, PA 19104 USA.; Fajgenbaum, DC (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. EM davidfa@mail.med.upenn.edu NR 9 TC 3 Z9 3 U1 2 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2352-3026 J9 LANCET HAEMATOL JI Lancet Haematol. PD APR PY 2016 VL 3 IS 4 BP E150 EP E152 DI 10.1016/S2352-3026(16)00007-7 PG 3 WC Hematology SC Hematology GA DK7VB UT WOS:000375133100002 PM 27063967 ER PT J AU Liu, AY Nabel, CS Finkelman, BS Ruth, JR Kurzrock, R van Rhee, F Krymskaya, VP Kelleher, D Rubenstein, AH Fajgenbaum, DC AF Liu, Amy Y. Nabel, Christopher S. Finkelman, Brian S. Ruth, Jason R. Kurzrock, Razelle van Rhee, Frits Krymskaya, Vera P. Kelleher, Dermot Rubenstein, Arthur H. Fajgenbaum, David C. TI Idiopathic multicentric Castleman's disease: a systematic literature review SO LANCET HAEMATOLOGY LA English DT Review ID ANTI-INTERLEUKIN-6 RECEPTOR ANTIBODY; SARCOMA-ASSOCIATED HERPESVIRUS; LYMPH-NODE HYPERPLASIA; KAPOSIS-SARCOMA; MONOCLONAL-ANTIBODY; DNA-SEQUENCES; POEMS SYNDROME; TAFRO SYNDROME; HIV-INFECTION; DOUBLE-BLIND AB Background Multicentric Castleman's disease describes a group of poorly understood lymphoproliferative disorders driven by proinflammatory hypercytokinaemia. Patients have heterogeneous clinical features, characteristic lymph node histopathology, and often deadly multiple organ dysfunction. Human herpesvirus 8 (HHV8) causes multicentric Castleman's disease in immunosuppressed patients. The cause of HHV8-negative multicentric Castleman's disease is idiopathic; such cases are called idiopathic multicentric Castleman's disease. An absence of centralised information about idiopathic multicentric Castleman's disease represents a major challenge for clinicians and researchers. We aimed to characterise clinical features of, treatments for, and outcomes of idiopathic multicentric Castleman's disease. Methods We did a systematic literature review and searched PubMed, the Cochrane database, and ClinicalTrials.gov from January, 1995, with keywords including "Castleman's disease" and "giant lymph node hyperplasia". Inclusion criteria were pathology-confirmed Castleman's disease in multiple nodes and minimum clinical and treatment information on individual patients. Patients with HHV8 or HIV infection or diseases known to cause Castleman-like histopathology were excluded. Findings Our search identified 626 (33%) patients with HHV8-negative multicentric Castleman's disease from 1923 cases of multicentric Castleman's disease. 128 patients with idiopathic multicentric Castleman's disease met all inclusion criteria for the systematic review. Furthermore, aggregated data for 127 patients with idiopathic multicentric Castleman's disease were presented from clinical trials, which were excluded from primary analyses because patient-level data were not available. Clinical features of idiopathic multicentric Castleman's disease included multicentric lymphadenopathy (128/128), anaemia (79/91), elevated C-reactive protein (65/79), hypergammaglobulinaemia (63/82), hypoalbuminaemia (57/63), elevated interleukin 6 (57/63), hepatomegaly or splenomegaly (52/67), fever (33/64), oedema, ascites, anasarca, or a combination (29/37), elevated soluble interleukin 2 receptor (20/21), and elevated VEGF (16/20). First-line treatments for idiopathic multicentric Castleman's disease included corticosteroids (47/128 [37%]), cytotoxic chemotherapy (47/128 [37%]), and anti-interleukin 6 therapy (11/128 [9%]). 49 (42%) of 116 patients failed first-line therapy, 2-year survival was 88% (95% CI 81-95; 114 total patients, 12 events, 36 censored), and 27 (22%) of 121 patients died by the end of their observed follow-up (median 29 months [IQR 12-50]). 24 (19%) of 128 patients with idiopathic multicentric Castleman's disease had a diagnosis of a separate malignant disease, significantly higher than the frequency expected in age-matched controls (6%). Interpretation Our systematic review provides comprehensive information about clinical features, treatment, and outcomes of idiopathic multicentric Castleman's disease, which accounts for at least 33% of all cases of multicentric Castleman's disease. Our findings will assist with prompt recognition, diagnostic criteria development, and effective management of the disease. C1 [Liu, Amy Y.; Fajgenbaum, David C.] Univ Penn, Translat Res Lab, Orphan Dis Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Nabel, Christopher S.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Finkelman, Brian S.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Ruth, Jason R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kurzrock, Razelle] UC San Diego Moores Canc Ctr, Ctr Personalized Therapy, La Jolla, CA USA. [Kurzrock, Razelle] UC San Diego Moores Canc Ctr, Clin Trials Off, La Jolla, CA USA. [van Rhee, Frits] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Krymskaya, Vera P.] Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Perelman Sch Med,Translat Res Lab, Philadelphia, PA 19104 USA. [Kelleher, Dermot] Univ British Columbia, Fac Med, Woodward Instruct Resource Ctr, Vancouver, BC, Canada. [Rubenstein, Arthur H.] Univ Penn, Dept Med, Div Endocrinol Diabet & Metab, Perelman Sch Med,Smilow Ctr Translat Res, Philadelphia, PA 19104 USA. [Fajgenbaum, David C.] Univ Penn, Dept Med, Div Hematol Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Fajgenbaum, DC (reprint author), Univ Penn, Perelman Sch Med, Translat Res Lab, Philadelphia, PA 19104 USA. EM davidfa@mail.med.upenn.edu OI Finkelman, Brian/0000-0002-4348-8208 FU Genentech; Merck Serono; Foundation Medicine; Pfizer; Guardant; Sequenom; Janssen FX DCF served on an advisory board for Janssen Pharmaceuticals, outside the submitted work. RK received research funds from Genentech, Merck Serono, Foundation Medicine, Pfizer, Guardant, and Sequenom, outside the submitted work; consultant fees from Sequenom, outside the submitted work; and has ownership interest in RScueRX, outside the submitted work. FvR received grants for research from Janssen, during this study; and served on an advisory board for Janssen, outside the submitted work. All other authors declare no competing interests. NR 58 TC 4 Z9 4 U1 5 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2352-3026 J9 LANCET HAEMATOL JI Lancet Haematol. PD APR PY 2016 VL 3 IS 4 BP E163 EP E175 DI 10.1016/S2352-3026(16)00006-5 PG 13 WC Hematology SC Hematology GA DK7VB UT WOS:000375133100009 PM 27063975 ER PT J AU Wang, ZH Pratts, SG Zhang, HP Spencer, PJ Yu, RC Tonsho, M Shah, JA Tanabe, T Powell, HR Huang, CA Madsen, JC Sachs, DH Wang, ZR AF Wang, Zhaohui Pratts, Shannon G. Zhang, Huiping Spencer, Philip J. Yu, Ruichao Tonsho, Makoto Shah, Jigesh A. Tanabe, Tatsu Powell, Harrison R. Huang, Christene A. Madsen, Joren C. Sachs, David H. Wang, Zhirui TI Treg depletion in non-human primates using a novel diphtheria toxin-based anti-human CCR4 immunotoxin SO MOLECULAR ONCOLOGY LA English DT Article DE NHP Treg; CCR4; Immunotoxin; Diphtheria toxin ID REGULATORY T-CELLS; VACCINATION AB Regulatory T cells (Treg) play an important role in modulating the immune response and has attracted increasing attention in diverse fields such as cancer treatment, transplantation and autoimmune diseases. CC chemokine receptor 4 (CCR4) is expressed on the majority of Tregs, especially on effector Tregs. Recently we have developed a diphtheria-toxin based anti-human CCR4 immunotoxin for depleting CCR4(+) cells in vivo. In this study, we demonstrated that the anti-human CCR4 immunotoxin bound and depleted monkey CCR4+ cells in vitro. We also demonstrated that the immunotoxin bound to the CCR4(+)Foxp3(+) monkey Tregs in vitro. In vivo studies performed in two naive cynomolgus monkeys revealed 78-89% CCR4(+)Foxp3(+) Treg depletion in peripheral blood lasting approximately 10 days. In lymph nodes, 89-96% CCR4(+)Foxp3(+) Tregs were depleted. No effect was observed in other cell populations including CD8(+) T cells, other CD4(+) T cells, B cells and NK cells. To our knowledge, this is the first agent that effectively depleted non-human primate (NHP) Tregs. This immunotoxin has potential to deplete effector Tregs for combined cancer treatment. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Wang, Zhaohui; Pratts, Shannon G.; Zhang, Huiping; Spencer, Philip J.; Yu, Ruichao; Tonsho, Makoto; Shah, Jigesh A.; Tanabe, Tatsu; Powell, Harrison R.; Huang, Christene A.; Madsen, Joren C.; Sachs, David H.; Wang, Zhirui] Massachusetts Gen Hosp, Ctr Transplantat Sci, Bldg 149-6113 13th St, Boston, MA 02129 USA. [Wang, Zhaohui; Pratts, Shannon G.; Zhang, Huiping; Spencer, Philip J.; Yu, Ruichao; Tonsho, Makoto; Shah, Jigesh A.; Tanabe, Tatsu; Powell, Harrison R.; Huang, Christene A.; Madsen, Joren C.; Sachs, David H.; Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA USA. [Sachs, David H.] Massachusetts Gen Hosp, Ctr Transplantat Sci, TBRC Labs, Boston, MA 02114 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Wang, ZR (reprint author), Massachusetts Gen Hosp, Ctr Transplantat Sci, Bldg 149-6113 13th St, Boston, MA 02129 USA.; Wang, ZR (reprint author), Harvard Univ, Med Sch MGH East, Bldg 149-6113 13th St, Boston, MA 02129 USA. EM zwang7@mgh.harvard.edu FU NIH/NIAID [R00000000004616] FX We would like to thank Joanne Morris for veterinary support and lymph node biopsies, Isabel M. Hanekamp, James A. Winter, Elena Shubina, Sarah Lofgren and Matthew Defazio for their technical assistance. This study was supported by NIH/NIAID (non-human primate opportunities pool 2014) R00000000004616 (to Z. W. and D. H. S). NR 16 TC 2 Z9 2 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD APR PY 2016 VL 10 IS 4 BP 553 EP 565 DI 10.1016/j.molonc.2015.11.008 PG 13 WC Oncology SC Oncology GA DK4UO UT WOS:000374916000005 PM 26643572 ER PT J AU Crommentuijn, MHW Maguire, CA Niers, JM Vanclertop, WP Badr, CE Wurdinger, T Tannous, BA AF Crommentuijn, Matheus H. W. Maguire, Casey A. Niers, Johanna M. Vanclertop, W. Peter Badr, Christian E. Wurdinger, Thomas Tannous, Bakhos A. TI Intracranial AAV-sTRAIL combined with lanatoside C prolongs survival in an orthotopic xenograft mouse model of invasive glioblastoma SO MOLECULAR ONCOLOGY LA English DT Article DE Glioblastoma; TRAIL; Adeno-associated virus; Gene therapy; Cardiac glycoside; Lanatoside C ID APOPTOSIS-INDUCING LIGAND; TRAIL-INDUCED APOPTOSIS; MALIGNANT GLIOMA-CELLS; CARDIAC-GLYCOSIDES; NERVOUS-SYSTEM; VIRUS VECTORS; GENE DELIVERY; UP-REGULATION; TUMOR-CELLS; STEM-CELLS AB Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of secreted, soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) to GBM tumors in mice and combined it with the TRAIL-sensitizing cardiac glycoside, lanatoside C (lan C). We applied this combined therapy to two different GBM models using human U87 glioma cells and primary patient-derived GBM neural spheres in culture and in orthotopic GBM xenograft models in mice. In U87 cells, conditioned medium from AAV2-sTRAIL expressing cells combined with Ian C induced 80% cell death. Similarly, lan C sensitized primary GBM spheres to sTRAIL causing over 90% cell death. In mice bearing intracranial U87 tumors treated with AAVrh.8-sTRAIL, administration of lan C caused a decrease in tumor associated Fluc signal, while tumor size increased within days of stopping the treatment. Another round of lan C treatment re-sensitized GBM tumor to sTRAIL-induced cell death. AAVrh.8-sTRAIL treatment alone and combined with lanatoside C resulted in a significant decrease in tumor growth and longer survival of mice bearing orthotopic invasive GBM brain tumors. In summary, AAV-sTRAIL combined with lanatoside C induced cell death in U87 glioma cells and patient-derived GBM neural spheres in culture and in vivo leading to an increased in overall mice survival. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Crommentuijn, Matheus H. W.; Maguire, Casey A.; Niers, Johanna M.; Badr, Christian E.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Neurosci Ctr, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA. [Crommentuijn, Matheus H. W.; Maguire, Casey A.; Niers, Johanna M.; Badr, Christian E.; Wurdinger, Thomas; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Crommentuijn, Matheus H. W.; Niers, Johanna M.; Vanclertop, W. Peter; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Canc Ctr Amsterdam, Neurooncol Res Grp, Amsterdam, Netherlands. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Neurosci Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu OI Crommentuijn, Matheus/0000-0001-8217-5370 FU National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke (NINDS) [R01NS064983]; National Cancer Institute (NCI) [R01CA166077]; American Brain Tumor Association Discovery Grant; NIH/NINDS [R21NS081374, P30NS045776]; Shared Instrumentation Grant IVIS imaging system [1S10RR025504]; KWF Kankerbestrijding (Dutch Cancer Society) FX This study was supported by grants from the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke (NINDS) R01NS064983 and the National Cancer Institute (NCI) R01CA166077 (BAT), the American Brain Tumor Association Discovery Grant and NIH/NINDS R21NS081374 (CM). The authors acknowledge the support from 1S10RR025504 Shared Instrumentation Grant IVIS imaging system that was used to acquire imaging data. M.H.W.C. was supported by a scholarship from KWF Kankerbestrijding (Dutch Cancer Society). The authors would like to thank Kevin Conway for the production of lentivirus vectors at the MGH Vector Core, Charlestown, MA, USA (supported by NIH/NINDS P30NS045776; BAT). NR 31 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD APR PY 2016 VL 10 IS 4 BP 625 EP 634 DI 10.1016/j.molonc.2015.11.011 PG 10 WC Oncology SC Oncology GA DK4UO UT WOS:000374916000011 PM 26708508 ER PT J AU Choudhury, SR Harris, AF Cabral, DJ Keeler, AM Sapp, E Ferreira, JS Gray-Edwards, HL Johnson, JA Johnson, AK Su, Q Stoica, L DiFiglia, M Aronin, N Martin, DR Gao, G Sena-Esteves, M AF Choudhury, Sourav R. Harris, Anne F. Cabral, Damien J. Keeler, Allison M. Sapp, Ellen Ferreira, Jennifer S. Gray-Edwards, Heather L. Johnson, Jacob A. Johnson, Aime K. Su, Qin Stoica, Lorelei DiFiglia, Marian Aronin, Neil Martin, Douglas R. Gao, Guangping Sena-Esteves, Miguel TI Widespread Central Nervous System Gene Transfer and Silencing After Systemic Delivery of Novel AAV-AS Vector SO MOLECULAR THERAPY LA English DT Article ID ADENOASSOCIATED VIRUS VECTORS; CONVECTION-ENHANCED DELIVERY; HUNTINGTONS-DISEASE MICE; BLOOD-BRAIN-BARRIER; NONHUMAN-PRIMATES; VIRAL VECTORS; MOUSE MODEL; ADULT MICE; DIRECTED EVOLUTION; PERIPHERAL-TISSUES AB Effective gene delivery to the central nervous system (CNS) is vital for development of novel gene therapies for neurological diseases. Adeno-associated virus (AAV) vectors have emerged as an effective platform for in vivo gene transfer, but overall neuronal transduction efficiency of vectors derived from naturally occurring AAV capsids after systemic administration is relatively low. Here, we investigated the possibility of improving CNS transduction of existing AAV capsids by genetically fusing peptides to the N-terminus of VP2 capsid protein. A novel vector AAV-AS, generated by the insertion of a poly-alanine peptide, is capable of extensive gene transfer throughout the CNS after systemic administration in adult mice. AAV-AS is 6- and 15-fold more efficient than AAV9 in spinal cord and cerebrum, respectively. The neuronal transduction profile varies across brain regions but is particularly high in the striatum where AAV-AS transduces 36% of striatal neurons. Widespread neuronal gene transfer was also documented in cat brain and spinal cord. A single intravenous injection of an AAV-AS vector encoding an artificial microRNA targeting huntingtin (Htt) resulted in 33-50% knockdown of Htt across multiple CNS structures in adult mice. This novel AAV-AS vector is a promising platform to develop new gene therapies for neurodegenerative disorders. C1 [Choudhury, Sourav R.; Harris, Anne F.; Cabral, Damien J.; Keeler, Allison M.; Ferreira, Jennifer S.; Stoica, Lorelei; Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. [Choudhury, Sourav R.; Harris, Anne F.; Cabral, Damien J.; Keeler, Allison M.; Ferreira, Jennifer S.; Su, Qin; Stoica, Lorelei; Gao, Guangping; Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Gene Therapy Ctr, 368 Plantat St,ASC6-2055, Worcester, MA 01605 USA. [Sapp, Ellen; DiFiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Gray-Edwards, Heather L.; Martin, Douglas R.] Auburn Univ, Coll Vet Med, Scott Ritchey Res Ctr, Auburn, AL 36849 USA. [Johnson, Jacob A.; Johnson, Aime K.] Auburn Univ, Coll Vet Med, Dept Clin Sci, Auburn, AL 36849 USA. [Su, Qin; Gao, Guangping] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01605 USA. [Aronin, Neil] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. [Aronin, Neil] Univ Massachusetts, Sch Med, RNA Therapeut Inst, Worcester, MA 01605 USA. [Martin, Douglas R.] Auburn Univ, Coll Vet Med, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. RP Sena-Esteves, M (reprint author), Univ Massachusetts, Sch Med, Gene Therapy Ctr, 368 Plantat St,ASC6-2055, Worcester, MA 01605 USA. EM miguel.esteves@umassmed.edu FU National Institutes of Health [R01NS066310, R01NS38194]; CHDI Foundation, Inc FX The authors thank Brian D'Amore, Erica Mondo, Owen Peters and Lori Kennington for technical assistance, Eric Mick for statistical consultation, and Robert Kotin for critically reading the manuscript. This work was supported by grants R01NS066310 (M.S.-E.) and R01NS38194 (N.A.) from the National Institutes of Health and in part by CHDI Foundation, Inc. G.G. is a founder of Voyager Therapeutics and holds equity in the company. G.G. is an inventor on patents licensed to Voyager Therapeutics. NR 63 TC 9 Z9 9 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD APR PY 2016 VL 24 IS 4 BP 726 EP 735 DI 10.1038/mt.2015.231 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA DJ7EO UT WOS:000374374900013 PM 26708003 ER PT J AU Karimi, M Mirshekari, H Aliakbari, M Sahandi-Zangabad, P Hamblin, MR AF Karimi, Mahdi Mirshekari, Hamed Aliakbari, Masoumeh Sahandi-Zangabad, Parham Hamblin, Michael R. TI Smart mesoporous silica nanoparticles for controlled-release drug delivery SO NANOTECHNOLOGY REVIEWS LA English DT Review DE drug delivery systems; enzyme; light-responsive nanocarriers; magnetic; mesoporous silica nanoparticles; pH; redox; stimuli responsive; temperature ID COATED GOLD NANORODS; BIOMEDICAL APPLICATIONS; MAGNETIC NANOPARTICLES; COLLOIDAL SILICA; CANCER-TREATMENT; IN-VITRO; PLATFORM; HYBRID; CELLS; NANOCOMPOSITES AB Stimuli-responsive controlled-release nanocarriers are promising vehicles for delivery of bioactive molecules that can minimize side effects and maximize efficiency. The release of the drug occurs when the nanocarrier is triggered by an internal or external stimulus. Mesoporous silica nanoparticles (MSN) can have drugs and bioactive cargos loaded into the high-capacity pores, and their release can be triggered by activation of a variety of stimulus-responsive molecular "gatekeepers" or "nanovalves." In this mini-review, we discuss the basic concepts of MSN in targeted drug-release systems and cover different stimulus-responsive gatekeepers. Internal stimuli include redox, enzymes, and pH, while external stimuli include light, ultrasound, and magnetic fields, and temperature can either be internal or external. C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Karimi, Mahdi] Iran Univ Med Sci, Fac Adv Technol Med, Dept Med Nanotechnol, Tehran, Iran. [Mirshekari, Hamed] Iran Univ Med Sci, ANNRG, Tehran, Iran. [Aliakbari, Masoumeh] Kerman Univ Med Sci, Med Lab Sci, Kerman, Iran. [Sahandi-Zangabad, Parham] Sharif Univ Technol, Dept Mat Sci & Engn, POB 11365-9466, Tehran 14588, Iran. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Hamblin, MR (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.; Hamblin, MR (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM hamblin@helix.mgh.harvard.edu OI Sahandi Zangabad, Parham /0000-0001-8316-6732 FU US NIH grant [R01AI050875] FX MRH was supported by US NIH grant R01AI050875. The authors gratefully extend their appreciation to Mahnaz Bozorgomid for illustrating the schematic figure. NR 85 TC 8 Z9 8 U1 40 U2 91 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2191-9089 EI 2191-9097 J9 NANOTECHNOL REV JI Nanotechnol. Rev. PD APR PY 2016 VL 5 IS 2 BP 195 EP 207 DI 10.1515/ntrev-2015-0057 PG 13 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DK6PO UT WOS:000375046800002 ER PT J AU Absalon, S Robbins, JA Dvorin, JD AF Absalon, Sabrina Robbins, Jonathan A. Dvorin, Jeffrey D. TI An essential malaria protein defines the architecture of blood-stage and transmission-stage parasites SO NATURE COMMUNICATIONS LA English DT Article ID INNER MEMBRANE COMPLEX; PLASMODIUM-FALCIPARUM MEROZOITES; HOST-CELL INVASION; TOXOPLASMA-GONDII; APICOMPLEXAN PARASITES; GENE-EXPRESSION; MOTILITY; ERYTHROCYTES; IDENTIFICATION; KINASE AB Blood-stage replication of the human malaria parasite Plasmodium falciparum occurs via schizogony, wherein daughter parasites are formed by a specialized cytokinesis known as segmentation. Here we identify a parasite protein, which we name P. falciparum Merozoite Organizing Protein (PfMOP), as essential for cytokinesis of blood-stage parasites. We show that, following PfMOP knockdown, parasites undergo incomplete segmentation resulting in a residual agglomerate of partially divided cells. While organelles develop normally, the structural scaffold of daughter parasites, the inner membrane complex (IMC), fails to form in this agglomerate causing flawed segmentation. In PfMOP-deficient gametocytes, the IMC formation defect causes maturation arrest with aberrant morphology and death. Our results provide insight into the mechanisms of replication and maturation of malaria parasites. C1 [Absalon, Sabrina; Robbins, Jonathan A.; Dvorin, Jeffrey D.] Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Absalon, Sabrina; Dvorin, Jeffrey D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Robbins, Jonathan A.] Brigham & Womens Hosp, Div Infect Dis, Massachusetts Gen Hosp, 75 Francis St, Boston, MA 02115 USA. RP Dvorin, JD (reprint author), Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.; Dvorin, JD (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. EM jeffrey.dvorin@childrens.harvard.edu OI Absalon, Sabrina/0000-0002-4167-3071 FU National Institutes of Health [R01AI102907, DP2AI112219, T32AI007061]; Charles H. Hood Foundation; Infectious Diseases Society of America Astellas Young Investigator Award FX We thank M.J. Gubbels, B. Coleman, E. Egan and V. Streva for critical reading of the manuscript. We thank O. Puijalon, M. Makler, A. Cowman, D. Richard, J. Thompson, K. Wycherley, R. Coppel, R. Anders, J. Rayner, A. Holder, S. Prigge and MR4 via contribution from J. Adams for provision of antibodies. We thank M. Ericsson (Electron Microscopy Facility), A. Hill (Cellular Imaging Core) and D. Richardson (Harvard Center for Biological Imaging) for core training and management. We thank M. Duraisingh for guidance and sharing of resources. This work was supported by grants from the National Institutes of Health R01AI102907 (J.D.D.), DP2AI112219 (J.D.D.), T32AI007061 (J.A.R.), the Charles H. Hood Foundation (J.D.D.) and the Infectious Diseases Society of America Astellas Young Investigator Award (J.D.D.). NR 59 TC 2 Z9 2 U1 4 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2016 VL 7 AR 11449 DI 10.1038/ncomms11449 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DK4NR UT WOS:000374895700001 PM 27121004 ER PT J AU Couch, FJ Kuchenbaecker, KB Michailidou, K Mendoza-Fandino, GA Nord, S Lilyquist, J Olswold, C Hallberg, E Agata, S Ahsan, H Aittomaki, K Ambrosone, C Andrulis, IL Anton-Culver, H Arndt, V Arun, BK Arver, B Barile, M Barkardottir, RB Barrowdale, D Beckmann, L Beckmann, MW Benitez, J Blank, SV Blomqvist, C Bogdanova, NV Bojesen, SE Bolla, MK Bonanni, B Brauch, H Brenner, H Burwinkel, B Buys, SS Caldes, T Caligo, MA Canzian, F Carpenter, J Chang-Claude, J Chanock, SJ Chung, WK Claes, KBM Cox, A Cross, SS Cunningham, JM Czene, K Daly, MB Damiola, F Darabi, H de la Hoya, M Devilee, P Diez, O Ding, YC Dolcetti, R Domchek, SM Dorfling, CM dos-Santos-Silva, I Dumont, M Dunning, AM Eccles, DM Ehrencrona, H Ekici, AB Eliassen, H Ellis, S Fasching, PA Figueroa, J Flesch-Janys, D Forsti, A Fostira, F Foulkes, WD Friebel, T Friedman, E Frost, D Gabrielson, M Gammon, MD Ganz, PA Gapstur, SM Garber, J Gaudet, MM Gayther, SA Gerdes, AM Ghoussaini, M Giles, GG Glendon, G Godwin, AK Goldberg, MS Goldgar, DE Gonzalez-Neira, A Greene, MH Gronwald, J Guenel, P Gunter, M Haeberle, L Haiman, CA Hamann, U Hansen, TVO Hart, S Healey, S Heikkinen, T Henderson, BE Herzog, J Hogervorst, FBL Hollestelle, A Hooning, MJ Hoover, RN Hopper, JL Humphreys, K Hunter, DJ Huzarski, T Imyanitov, EN Isaacs, C Jakubowska, A James, P Janavicius, R Jensen, UB John, EM Jones, M Kabisch, M Kar, S Karlan, BY Khan, S Khaw, KT Kibriya, MG Knight, JA Ko, YD Konstantopoulou, I Kosma, VM Kristensen, V Kwong, A Laitman, Y Lambrechts, D Lazaro, C Lee, E Le Marchand, L Lester, J Lindblom, A Lindor, N Lindstrom, S Liu, J Long, J Lubinski, J Mai, PL Makalic, E Malone, KE Mannermaa, A Manoukian, S Margolin, S Marme, F Martens, JWM McGuffog, L Meindl, A Miller, A Milne, RL Miron, P Montagna, M Mazoyer, S Mulligan, AM Muranen, TA Nathanson, KL Neuhausen, SL Nevanlinna, H Nordestgaard, BG Nussbaum, RL Offit, K Olah, E Olopade, OI Olson, JE Osorio, A Park, SK Peeters, PH Peissel, B Peterlongo, P Peto, J Phelan, CM Pilarski, R Poppe, B Pylkas, K Radice, P Rahman, N Rantala, J Rappaport, C Rennert, G Richardson, A Robson, M Romieu, I Rudolph, A Rutgers, EJ Sanchez, MJ Santella, RM Sawyer, EJ Schmidt, DF Schmidt, MK Schmutzler, RK Schumacher, F Scott, R Senter, L Sharma, P Simard, J Singer, CF Sinilnikova, OM Soucy, P Southey, M Steinemann, D Stenmark-Askmalm, M Stoppa-Lyonnet, D Swerdlow, A Szabo, CI Tamimi, R Tapper, W Teixeira, MR Teo, SH Terry, MB Thomassen, M Thompson, D Tihomirova, L Toland, AE Tollenaar, RAEM Tomlinson, I Truong, T Tsimiklis, H Teule, A Tumino, R Tung, N Turnbull, C Ursin, G van Deurzen, CHM van Rensburg, EJ Varon-Mateeva, R Wang, ZM Wang-Gohrke, S Weiderpass, E Weitzel, JN Whittemore, A Wildiers, H Winqvist, R Yang, XHR Yannoukakos, D Yao, S Zamora, MP Zheng, W Hall, P Kraft, P Vachon, C Slager, S Chenevix-Trench, G Pharoah, PDP Monteiro, AAN Garcia-Closas, M Easton, DF Antoniou, AC AF Couch, Fergus J. Kuchenbaecker, Karoline B. Michailidou, Kyriaki Mendoza-Fandino, Gustavo A. Nord, Silje Lilyquist, Janna Olswold, Curtis Hallberg, Emily Agata, Simona Ahsan, Habibul Aittomaeki, Kristiina Ambrosone, Christine Andrulis, Irene L. Anton-Culver, Hoda Arndt, Volker Arun, Banu K. Arver, Brita Barile, Monica Barkardottir, Rosa B. Barrowdale, Daniel Beckmann, Lars Beckmann, Matthias W. Benitez, Javier Blank, Stephanie V. Blomqvist, Carl Bogdanova, Natalia V. Bojesen, Stig E. Bolla, Manjeet K. Bonanni, Bernardo Brauch, Hiltrud Brenner, Hermann Burwinkel, Barbara Buys, Saundra S. Caldes, Trinidad Caligo, Maria A. Canzian, Federico Carpenter, Jane Chang-Claude, Jenny Chanock, Stephen J. Chung, Wendy K. Claes, Kathleen B. M. Cox, Angela Cross, Simon S. Cunningham, Julie M. Czene, Kamila Daly, Mary B. Damiola, Francesca Darabi, Hatef de la Hoya, Miguel Devilee, Peter Diez, Orland Ding, Yuan C. Dolcetti, Riccardo Domchek, Susan M. Dorfling, Cecilia M. dos-Santos-Silva, Isabel Dumont, Martine Dunning, Alison M. Eccles, Diana M. Ehrencrona, Hans Ekici, Arif B. Eliassen, Heather Ellis, Steve Fasching, Peter A. Figueroa, Jonine Flesch-Janys, Dieter Foersti, Asta Fostira, Florentia Foulkes, William D. Friebel, Tara Friedman, Eitan Frost, Debra Gabrielson, Marike Gammon, Marilie D. Ganz, Patricia A. Gapstur, Susan M. Garber, Judy Gaudet, Mia M. Gayther, Simon A. Gerdes, Anne-Marie Ghoussaini, Maya Giles, Graham G. Glendon, Gord Godwin, Andrew K. Goldberg, Mark S. Goldgar, David E. Gonzalez-Neira, Anna Greene, Mark H. Gronwald, Jacek Guenel, Pascal Gunter, Marc Haeberle, Lothar Haiman, Christopher A. Hamann, Ute Hansen, Thomas V. O. Hart, Steven Healey, Sue Heikkinen, Tuomas Henderson, Brian E. Herzog, Josef Hogervorst, Frans B. L. Hollestelle, Antoinette Hooning, Maartje J. Hoover, Robert N. Hopper, John L. Humphreys, Keith Hunter, David J. Huzarski, Tomasz Imyanitov, Evgeny N. Isaacs, Claudine Jakubowska, Anna James, Paul Janavicius, Ramunas Jensen, Uffe Birk John, Esther M. Jones, Michael Kabisch, Maria Kar, Siddhartha Karlan, Beth Y. Khan, Sofia Khaw, Kay-Tee Kibriya, Muhammad G. Knight, Julia A. Ko, Yon-Dschun Konstantopoulou, Irene Kosma, Veli-Matti Kristensen, Vessela Kwong, Ava Laitman, Yael Lambrechts, Diether Lazaro, Conxi Lee, Eunjung Le Marchand, Loic Lester, Jenny Lindblom, Annika Lindor, Noralane Lindstrom, Sara Liu, Jianjun Long, Jirong Lubinski, Jan Mai, Phuong L. Makalic, Enes Malone, Kathleen E. Mannermaa, Arto Manoukian, Siranoush Margolin, Sara Marme, Frederik Martens, John W. M. McGuffog, Lesley Meindl, Alfons Miller, Austin Milne, Roger L. Miron, Penelope Montagna, Marco Mazoyer, Sylvie Mulligan, Anna M. Muranen, Taru A. Nathanson, Katherine L. Neuhausen, Susan L. Nevanlinna, Heli Nordestgaard, Borge G. Nussbaum, Robert L. Offit, Kenneth Olah, Edith Olopade, Olufunmilayo I. Olson, Janet E. Osorio, Ana Park, Sue K. Peeters, Petra H. Peissel, Bernard Peterlongo, Paolo Peto, Julian Phelan, Catherine M. Pilarski, Robert Poppe, Bruce Pylkaes, Katri Radice, Paolo Rahman, Nazneen Rantala, Johanna Rappaport, Christine Rennert, Gad Richardson, Andrea Robson, Mark Romieu, Isabelle Rudolph, Anja Rutgers, Emiel J. Sanchez, Maria-Jose Santella, Regina M. Sawyer, Elinor J. Schmidt, Daniel F. Schmidt, Marjanka K. Schmutzler, Rita K. Schumacher, Fredrick Scott, Rodney Senter, Leigha Sharma, Priyanka Simard, Jacques Singer, Christian F. Sinilnikova, Olga M. Soucy, Penny Southey, Melissa Steinemann, Doris Stenmark-Askmalm, Marie Stoppa-Lyonnet, Dominique Swerdlow, Anthony Szabo, Csilla I. Tamimi, Rulla Tapper, William Teixeira, Manuel R. Teo, Soo-Hwang Terry, Mary B. Thomassen, Mads Thompson, Deborah Tihomirova, Laima Toland, Amanda E. Tollenaar, Robert A. E. M. Tomlinson, Ian Truong, Therese Tsimiklis, Helen Teule, Alex Tumino, Rosario Tung, Nadine Turnbull, Clare Ursin, Giski van Deurzen, Carolien H. M. van Rensburg, Elizabeth J. Varon-Mateeva, Raymonda Wang, Zhaoming Wang-Gohrke, Shan Weiderpass, Elisabete Weitzel, Jeffrey N. Whittemore, Alice Wildiers, Hans Winqvist, Robert Yang, Xiaohong R. Yannoukakos, Drakoulis Yao, Song Zamora, M. Pilar Zheng, Wei Hall, Per Kraft, Peter Vachon, Celine Slager, Susan Chenevix-Trench, Georgia Pharoah, Paul D. P. Monteiro, Alvaro A. N. Garcia-Closas, Montserrat Easton, Douglas F. Antoniou, Antonis C. TI Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; BRCA2 MUTATION CARRIERS; PANCREATIC-CANCER; COMMON VARIANTS; CONFER SUSCEPTIBILITY; GENE-EXPRESSION; TELOMERE LENGTH; RISK; METAANALYSIS; IDENTIFY AB Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction. C1 [Couch, Fergus J.; Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Couch, Fergus J.; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Hart, Steven; Olson, Janet E.; Vachon, Celine; Slager, Susan] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Kuchenbaecker, Karoline B.; Michailidou, Kyriaki; Barrowdale, Daniel; Bolla, Manjeet K.; Ellis, Steve; Frost, Debra; McGuffog, Lesley; Thompson, Deborah; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England. [Mendoza-Fandino, Gustavo A.; Phelan, Catherine M.; Monteiro, Alvaro A. N.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Canc Epidemiol Program, Tampa, FL 33612 USA. [Nord, Silje; Kristensen, Vessela] Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway. [Agata, Simona; Montagna, Marco] IRCCS, IOV, Immunol & Mol Oncol Unit, I-20133 Padua, Italy. [Ahsan, Habibul; Kibriya, Muhammad G.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Ahsan, Habibul] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA. [Ahsan, Habibul] Univ Chicago, Dept Med & Human Genet, Chicago, IL 60637 USA. [Aittomaeki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki 00029, Finland. [Ambrosone, Christine] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Andrulis, Irene L.; Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5B 1W8, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5B 1W8, Canada. [Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA. [Arndt, Volker; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Arver, Brita; Margolin, Sara] Karolinska Univ Hosp, Dept Oncol, SE-17176 Stockholm, Sweden. [Barile, Monica; Bonanni, Bernardo] Ist Europeo Oncol, Div Canc Prevent & Genet, I-20141 Milan, Italy. [Barkardottir, Rosa B.] Landspitali Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland. [Barkardottir, Rosa B.] Univ Iceland, Sch Med, IS-101 Reykjavik, Iceland. [Beckmann, Lars] Inst Qual & Efficiency Hlth Care IQWiG, D-50670 Cologne, Germany. [Beckmann, Matthias W.; Fasching, Peter A.; Haeberle, Lothar] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Breast Ctr Franconia, Dept Gynecol & Obstet,Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Benitez, Javier; Osorio, Ana] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Human Canc Genet Program, Madrid 28029, Spain. [Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Canc Genet Program, Genotyping Unit CeGen, Madrid 28029, Spain. [Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid 28029, Spain. [Blank, Stephanie V.] NYU, Sch Med, NYU Womens Canc Program, New York, NY 10016 USA. [Blomqvist, Carl] Univ Helsinki, Dept Oncol, FI-00029 Helsinki, Finland. [Blomqvist, Carl] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Finland. [Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany. [Bojesen, Stig E.; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, DK-2730 Herlev, Denmark. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany. [Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, D-69120 Heidelberg, Germany. [Brenner, Hermann] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany. [Burwinkel, Barbara; Heikkinen, Tuomas; Marme, Frederik; Muranen, Taru A.] Heidelberg Univ, Dept Obstet & Gynecol, D-69120 Heidelberg, Germany. [Buys, Saundra S.] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Caldes, Trinidad; de la Hoya, Miguel] IdISSC, Hosp Clin San Carlos, Mol Oncol Lab, Madrid 28040, Spain. [Caligo, Maria A.] Univ Pisa, Dept Lab Med, Sect Genet Oncol, I-56126 Pisa, Italy. [Caligo, Maria A.] Univ Hosp Pisa, I-56126 Pisa, Italy. [Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany. [Carpenter, Jane] Univ Sydney, Westmead Millennium Inst, Australian Breast Canc Tissue Bank, Sydney, NSW 2145, Australia. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Chanock, Stephen J.; Figueroa, Jonine; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat, New York, NY 10032 USA. [Chung, Wendy K.] Columbia Univ, Dept Med, New York, NY 10032 USA. [Claes, Kathleen B. M.; Poppe, Bruce] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium. [Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res Ctr, Sheffield S10 2RX, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield S10 2HQ, S Yorkshire, England. [Czene, Kamila; Darabi, Hatef; Gabrielson, Marike; Humphreys, Keith; Weiderpass, Elisabete; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Daly, Mary B.] Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA 19111 USA. [Damiola, Francesca; Mazoyer, Sylvie; Sinilnikova, Olga M.] Univ Lyon, CNRS, UMR5286, Ctr Rech Cancerol Lyon,INSERM,U1052, F-69373 Lyon, France. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Pathol, NL-2333 ZC Leiden, Netherlands. [Diez, Orland] Univ Hosp Vall dHebron, VHIO, Oncogenet Grp, Barcelona 08035, Spain. [Diez, Orland] Univ Autonoma Barcelona, Barcelona 08035, Spain. [Ding, Yuan C.; Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA. [Dolcetti, Riccardo] CRO Aviano Natl Canc Inst, Canc Bioimmunotherapy Unit, I-33081 Aviano, Italy. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0007 Pretoria, South Africa. [dos-Santos-Silva, Isabel; Peto, Julian] Univ London London Sch Hyg & Trop Med, Dept Non Communicable Dis Epidemiol, Keppel St, London WC1E 7HT, England. [Dumont, Martine] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ G1V 4G2, Canada. [Dumont, Martine] Univ Laval, Quebec City, PQ G1V 4G2, Canada. [Dunning, Alison M.; Ghoussaini, Maya; Kar, Siddhartha; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England. [Eccles, Diana M.; Tapper, William] Univ Southampton, Southampton Univ Hosp, Fac Med, Southampton SO16 6YD, Hants, England. [Ehrencrona, Hans] Uppsala Univ, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden. [Ehrencrona, Hans] Univ Lund Hosp, Dept Clin Genet, SE-22185 Lund, Sweden. [Ekici, Arif B.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Human Genet, D-91054 Erlangen, Germany. [Ekici, Arif B.] Comprehens Canc Ctr EMN, D-91054 Erlangen, Germany. [Eliassen, Heather; Tamimi, Rulla] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Eliassen, Heather; Tamimi, Rulla] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Eliassen, Heather; Lindstrom, Sara; Tamimi, Rulla; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, D-20246 Hamburg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany. [Foersti, Asta] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany. [Foersti, Asta] Lund Univ, Ctr Primary Hlth Care Res, SE-22100 Malmo, Sweden. [Fostira, Florentia; Konstantopoulou, Irene; Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, INRASTES, Mol Diagnost Lab, Athens 15310, Greece. [Foulkes, William D.] McGill Univ, Program Canc Genet, Montreal, PQ H3A 0G4, Canada. [Friebel, Tara] Univ Philadelphia, Philadelphia, PA 19104 USA. [Friedman, Eitan; Laitman, Yael] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Gammon, Marilie D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Ganz, Patricia A.] Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, UCLA Sch Med, Los Angeles, CA 90095 USA. [Ganz, Patricia A.] Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, UCLA Sch Publ Hlth, Los Angeles, CA 90095 USA. [Gapstur, Susan M.; Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA. [Garber, Judy] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02215 USA. [Gayther, Simon A.] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA. [Gerdes, Anne-Marie] Copenhagen Univ Hosp, Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark. [Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3010, Australia. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66205 USA. [Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ H3G 2M1, Canada. [Goldberg, Mark S.] McGill Univ, Ctr Hlth, Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H4A 3J1, Canada. [Goldgar, David E.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, Salt Lake City, UT 84132 USA. [Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid 28029, Spain. [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA. [Gronwald, Jacek; Huzarski, Tomasz; Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Guenel, Pascal; Truong, Therese] CESP Ctr Res Epidemiol & Populat Hlth, Inserm Natl Inst Hlth & Med Res, U1018, Environm Epidemiol Canc, F-70115 Villejuif, France. [Gunter, Marc] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England. [Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hamann, Ute; Kabisch, Maria] German Canc Res Ctr, Mol Genet Breast Canc, D-69120 Heidelberg, Germany. [Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, DK-2100 Copenhagen, Denmark. [Healey, Sue] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld 4029, Australia. [Heikkinen, Tuomas; Muranen, Taru A.] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Finland. [Herzog, Josef; Weitzel, Jeffrey N.] City Hope Clin Canc Genet Community Res Network, Clin Canc Genet, Duarte, CA 91010 USA. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, NL-1000 BE Amsterdam, Netherlands. [Hollestelle, Antoinette; Martens, John W. M.] Erasmus MC Canc Inst, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands. [Hooning, Maartje J.] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands. [Hopper, John L.; Makalic, Enes; Schmidt, Daniel F.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA. [Imyanitov, Evgeny N.] NN Petrov Oncol Res Inst, St Petersburg 197758, Russia. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [James, Paul] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic 8006, Australia. [James, Paul] Univ Melbourne, Dept Oncol, Melbourne, Vic 8006, Australia. [Janavicius, Ramunas] State Res Inst, Ctr Innovat Med, LT-08661 Vilnius, Lithuania. [Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, DK-8200 Aarhus N, Denmark. [John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA 94538 USA. [Jones, Michael; Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England. [Karlan, Beth Y.; Lester, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Khan, Sofia; Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, FI-00029 Helsinki, Finland. [Khan, Sofia; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Finland. [Khaw, Kay-Tee] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Ko, Yon-Dschun] Evangel Kliniken Bonn gGmbH, Johanniter Krankenhaus, Dept Internal Med, D-53113 Bonn, Germany. [Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, FI-70211 Kuopio, Finland. [Kwong, Ava] Hong Kong Hereditary Breast Canc Family Registry, Canc Genet Ctr, Hong Kong Sanat & Hosp, Hong Kong, Hong Kong, Peoples R China. [Kwong, Ava] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China. [Lambrechts, Diether] VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium. [Lazaro, Conxi] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Mol Diagnost Unit, Barcelona 08908, Spain. [Lee, Eunjung] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90032 USA. [Le Marchand, Loic] Univ Canc Ctr, Canc Epidemiol Program, Honolulu, HI 96813 USA. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, SE-17177 Stockholm, Sweden. [Lindor, Noralane] Mayo Clin, Hlth Sci Res, Scotsdale, AZ 85259 USA. [Lindstrom, Sara; Tamimi, Rulla; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [Liu, Jianjun] Genome Inst Singapore, Div Human Genet, Singapore 138672, Singapore. [Long, Jirong; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37203 USA. [Long, Jirong; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37203 USA. [Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Malone, Kathleen E.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Manoukian, Siranoush; Peissel, Bernard] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, I-20133 Milan, Italy. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, D-81675 Munich, Germany. [Miller, Austin] Roswell Pk Canc Inst, NRG Oncol Stat & Data Management Ctr, Buffalo, NY 14263 USA. [Miron, Penelope] Case Western Reserve Univ, Sch Med, Dept Genom & Genome Sci, Cleveland, OH 44106 USA. [Mulligan, Anna M.] Univ Hlth Network, Lab Med Program, Toronto, ON M5B 1W8, Canada. [Mulligan, Anna M.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5B 1W8, Canada. [Nussbaum, Robert L.] Invitae Corp, San Francisco, CA 94107 USA. [Offit, Kenneth; Robson, Mark] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Olah, Edith] Natl Inst Oncol, Dept Mol Genet, H-1122 Budapest, Hungary. [Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [Park, Sue K.] Seoul Natl Univ, Coll Med, Dept Prevent Med & Biomed Sci, Seoul 110799, South Korea. [Park, Sue K.] Seoul Natl Univ, Canc Res Inst, Seoul 110799, South Korea. [Peeters, Petra H.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, NL-3508 GA Utrecht, Netherlands. [Peeters, Petra H.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London SW7 2AZ, England. [Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, I-20133 Milan, Italy. [Pilarski, Robert; Senter, Leigha] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA. [Pylkaes, Katri; Winqvist, Robert] Univ Oulu, NordLab Oulu, Oulu Univ Hosp, Lab Canc Genet & Tumor Biol,Dept Clin Chem, FI-90220 Oulu, Finland. [Pylkaes, Katri; Winqvist, Robert] Univ Oulu, NordLab Oulu, Oulu Univ Hosp, Lab Canc Genet & Tumor Biol,Dept Clin Chem, FI-90220 Oulu, Finland. [Pylkaes, Katri; Winqvist, Robert] Univ Oulu, NordLab Oulu, Oulu Univ Hosp, Lab Canc Genet & Tumor Biol,Bioctr Oulu, FI-90220 Oulu, Finland. [Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy. [Rahman, Nazneen; Turnbull, Clare] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. [Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, SE-17176 Stockholm, Sweden. [Rappaport, Christine; Singer, Christian F.] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, A-1090 Vienna, Austria. [Rennert, Gad] Clalit Natl Israeli Canc Control Ctr, IL-34362 Haifa, Israel. [Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, IL-34362 Haifa, Israel. [Rennert, Gad] B Rappaport Fac Med, IL-34362 Haifa, Israel. [Richardson, Andrea] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Romieu, Isabelle] Int Agcy Res Canc, F-69008 Lyon, France. [Rutgers, Emiel J.; Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1006 BE Amsterdam, Netherlands. [Sanchez, Maria-Jose] Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, E-18014 Granada, Spain. [Sanchez, Maria-Jose] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain. [Santella, Regina M.] Columbia Univ, Dept Environm Hlth Sci, New York, NY 10032 USA. [Sawyer, Elinor J.] Kings Coll London, Guys Hosp, Div Canc Studies, Res Oncol, London SE1 9RT, England. [Schmutzler, Rita K.] Univ Hosp Cologne, Fac Med, Ctr Hereditary Breast & Ovarian Canc, D-50931 Cologne, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Fac Med, CIO, D-50931 Cologne, Germany. Univ Cologne, CMMC, D-50931 Cologne, Germany. [Scott, Rodney] John Hunter Hosp, Hunter Area Pathol Serv, Div Genet, Newcastle, NSW 2305, Australia. [Sharma, Priyanka] Univ Kansas, Med Ctr, Dept Hematol & Oncol, Kansas City, KS 66205 USA. [Simard, Jacques; Soucy, Penny] Univ Laval, Ctr Hosp Univ Quebec, Res Ctr, Quebec City, PQ G1V 4G2, Canada. [Sinilnikova, Olga M.] Hosp Civils Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France. [Southey, Melissa; Tsimiklis, Helen] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Steinemann, Doris] Hannover Med Sch, D-30625 Hannover, Germany. [Stenmark-Askmalm, Marie] Linkoping Univ, Dept Clin & Expt Med, Div Clin Genet, SE-58185 Linkoping, Sweden. [Stoppa-Lyonnet, Dominique] Inst Curie, Dept Tumour Biol, F-75248 Paris, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Sorbonne Paris Cite, F-75248 Paris, France. [Szabo, Csilla I.] NHGRI, NIH, Bethesda, MD 20892 USA. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, P-4200072 Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4200072 Oporto, Portugal. [Teo, Soo-Hwang] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya 47500, Malaysia. [Teo, Soo-Hwang] Univ Malaya, Med Ctr, Canc Res Inst, Fac Med, Kuala Lumpur 50603, Malaysia. [Terry, Mary B.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark. [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, LV-1067 Riga, Latvia. [Toland, Amanda E.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, NL-2333 ZC Leiden, Netherlands. [Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX3 7BN, England. [Teule, Alex] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Barcelona 08908, Spain. [Tumino, Rosario] Civ MP Arezzo Hosp, Canc Registry, I-97100 Asp Ragusa, Italy. [Tumino, Rosario] Civ MP Arezzo Hosp, Histopathol Unit, I-97100 Asp Ragusa, Italy. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Ursin, Giski; Weiderpass, Elisabete] Inst Populat Based Canc Res, Canc Registry Norway, N-0304 Oslo, Norway. [van Deurzen, Carolien H. M.] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Pathol, NL-3000 CA Rotterdam, Netherlands. [Varon-Mateeva, Raymonda] Charite, Inst Human Genet, D-13353 Berlin, Germany. [Wang, Zhaoming] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Gaithersburg, MD 20877 USA. [Wang-Gohrke, Shan] Univ Hosp Ulm, D-89075 Ulm, Germany. [Weiderpass, Elisabete] Univ Tromso, Fac Hlth Sci, Dept Community Med, N-9037 Tromso, Norway. [Weiderpass, Elisabete] Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki 2016, Finland. [Whittemore, Alice] Stanford Univ, Sch Med, Dept Hlth Res Policy Epidemiol, Stanford, CA 94305 USA. [Wildiers, Hans] Univ Hosp, Dept Gen Med Oncol, Multidisciplinary Breast Ctr, B-3000 Leuven, Belgium. [Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zamora, M. Pilar] Hosp Univ La Paz, Med Oncol Serv, Madrid 28046, Spain. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld 4029, Australia. [Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA. RP Couch, FJ (reprint author), Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.; Couch, FJ (reprint author), Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. EM couch.fergus@mayo.edu RI Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Nord, Silje/R-5212-2016; Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; montagna, marco/E-2225-2012; Osorio, Ana/I-4324-2014; Weiderpass, Elisabete/M-4029-2016; Teo, Soo-hwang/H-2353-2014; Knight, Julia/A-6843-2012; Zheng, Wei/O-3351-2013 OI Ehrencrona, Hans/0000-0002-5589-3622; Khan, Sofia/0000-0003-4185-8882; Muranen, Taru/0000-0002-5895-1808; Yannoukakos, Drakoulis/0000-0001-7509-3510; Dunning, Alison Margaret/0000-0001-6651-7166; Giles, Graham/0000-0003-4946-9099; Nord, Silje/0000-0002-3271-5356; Gronwald, Jacek/0000-0002-3643-2871; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; montagna, marco/0000-0002-4929-2150; Dolcetti, Riccardo/0000-0003-1625-9853; Osorio, Ana/0000-0001-8124-3984; Weiderpass, Elisabete/0000-0003-2237-0128; Zheng, Wei/0000-0003-1226-070X FU European Community Seventh Framework Programme [223175, HEALTH-F2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/A10710, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C12292/A11174]; National Institutes of Health [CA116201, CA128978, CA176785, CA192393]; National Institutes of Health, Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; National Institutes of Health, GAME-ON initiative; Canadian Institutes of Health Research (CIHR); Breast Cancer Res. Foundation; Ovarian Cancer Research Fund; Department of Defence [W81XWH-10-1-0341]; Florida Breast Cancer Foundation FX B.C.A.C. was funded through a European Community Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS); Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692); the National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), R01 grants (CA128978, CA176785, CA192393), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative); the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Breast Cancer Res. Foundation, and the Ovarian Cancer Research Fund. CIMBA genotyping was supported by National Institutes of Health grant (CA128978); the Department of Defence (W81XWH-10-1-0341); and the Breast Cancer Res. Foundation. CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. This study made use of data generated by the Wellcome Trust Case Control consortium. Functional studies were supported by the Florida Breast Cancer Foundation. A full description of funding and acknowledgments is provided in Supplementary Note 1. NR 48 TC 4 Z9 4 U1 12 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2016 VL 7 AR 11375 DI 10.1038/ncomms11375 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DK4NF UT WOS:000374894400001 PM 27117709 ER PT J AU Freedman, JE Gerstein, M Mick, E Rozowsky, J Levy, D Kitchen, R Das, S Shah, R Danielson, K Beaulieu, L Navarro, FCP Wang, YY Galeev, TR Holman, A Kwong, RY Murthy, V Tanriverdi, SE Koupenova-Zamor, M Mikhalev, E Tanriverdi, K AF Freedman, Jane E. Gerstein, Mark Mick, Eric Rozowsky, Joel Levy, Daniel Kitchen, Robert Das, Saumya Shah, Ravi Danielson, Kirsty Beaulieu, Lea Navarro, Fabio C. P. Wang, Yaoyu Galeev, Timur R. Holman, Alex Kwong, Raymond Y. Murthy, Venkatesh Tanriverdi, Selim E. Koupenova-Zamor, Milka Mikhalev, Ekaterina Tanriverdi, Kahraman TI Diverse human extracellular RNAs are widely detected in human plasma SO NATURE COMMUNICATIONS LA English DT Article ID SEQUENCING EXPERIMENTS; CIRCULATING MICRORNAS; SMALL NUCLEOLAR; C-ELEGANS; EXPRESSION; BIOMARKERS; PLATELET; DATABASE; BLOOD; TRANSCRIPTOME AB There is growing appreciation for the importance of non-protein-coding genes in development and disease. Although much is known about microRNAs, limitations in bioinformatic analyses of RNA sequencing have precluded broad assessment of other forms of small-RNAs in humans. By analysing sequencing data from plasma-derived RNA from 40 individuals, here we identified over a thousand human extracellular RNAs including microRNAs, piwi-interacting RNA (piRNA), and small nucleolar RNAs. Using a targeted quantitative PCR with reverse transcription approach in an additional 2,763 individuals, we characterized almost 500 of the most abundant extracellular transcripts including microRNAs, piRNAs and small nucleolar RNAs. The presence in plasma of many non-microRNA small-RNAs was confirmed in an independent cohort. We present comprehensive data to demonstrate the broad and consistent detection of diverse classes of circulating non-cellular small-RNAs from a large population. C1 [Freedman, Jane E.; Beaulieu, Lea; Tanriverdi, Selim E.; Koupenova-Zamor, Milka; Mikhalev, Ekaterina; Tanriverdi, Kahraman] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01605 USA. [Gerstein, Mark; Rozowsky, Joel; Kitchen, Robert; Navarro, Fabio C. P.; Galeev, Timur R.] Yale Univ, Sch Med, Computat Biol & Bioinformat Program, 333 Cedar St, New Haven, CT 06520 USA. [Mick, Eric] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01605 USA. [Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Levy, Daniel] NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20824 USA. [Das, Saumya; Shah, Ravi; Danielson, Kirsty] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Wang, Yaoyu; Holman, Alex] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA. [Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. [Murthy, Venkatesh] Univ Michigan, Ann Arbor, MI 48409 USA. RP Freedman, JE (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01605 USA. EM jane.freedman@umassmed.edu OI Navarro, Fabio/0000-0002-5640-9070; Murthy, Venkatesh/0000-0002-7901-1321; Rozowsky, Joel/0000-0002-3565-0762 FU NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director [N01-HC 25195, P01-HL085381, UH2TR000921, U01HL126495, UH2TR000901] FX This work was supported by N01-HC 25195, P01-HL085381 (to J.E.F.); UH2TR000921, U01HL126495 (to J.E.F.); and UH2TR000901 (to S.D.), that are supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director. We thank Lillian Kuo, Danilo Tagle and Pothur Srinivas of the NIH Common Fund for their assistance and guidance. NR 48 TC 13 Z9 13 U1 4 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2016 VL 7 AR 11106 DI 10.1038/ncomms11106 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DK4MK UT WOS:000374892300001 PM 27112789 ER PT J AU Hotta, R Cheng, LS Graham, HK Pan, W Nagy, N Belkind-Gerson, J Goldstein, AM AF Hotta, R. Cheng, L. S. Graham, H. K. Pan, W. Nagy, N. Belkind-Gerson, J. Goldstein, A. M. TI Isogenic enteric neural progenitor cells can replace missing neurons and glia in mice with Hirschsprung disease SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE cell therapy; endothelin receptor B; enteric nervous system; Hirschsprung disease; Lentivirus ID ENDOTHELIN RECEPTOR-B; CREST STEM-CELLS; NERVOUS-SYSTEM PROGENITORS; IN-VITRO; REGENERATIVE MEDICINE; ORGAN-CULTURE; GUT; MOUSE; TRANSPLANTATION; THERAPIES AB Background Transplanting autologous patient-derived enteric neuronal stem/progenitor cells (ENSCs) is an innovative approach to replacing missing enteric neurons in patients with Hirschsprung disease (HSCR). Using autologous cells eliminates immunologic and ethical concerns raised by other cell sources. However, whether postnatal aganglionic bowel is permissive for transplanted ENSCs and whether ENSCs from HSCR patients can be successfully isolated, cultured, and transplanted in vivo remains unknown. Methods ENSCs isolated from the ganglionic intestine of Ednrb(-/-) mice (HSCR-ENSCs) were characterized immunohistochemically and evaluated for their capacity to proliferate and differentiate in vitro. Fluorescently labeled ENSCs were co-cultured ex vivo with aganglionic Ednrb(-/-) colon. For in vivo transplantation, HSCR-ENSCs were labeled with lentivirus expressing green fluorescent protein (GFP) and implanted into aganglionic embryonic chick gut in ovo and postnatal aganglionic Ednrb(-/-) rectum in vivo. Key Results HSCR-ENSCs maintain normal capacity self-renewal and neuronal differentiation. Moreover, the Ednrb(-/-) aganglionic environment is permissive to engraftment by wild-type ENSCs ex vivo and supports migratrion and neuroglial differentiation of these cells following transplantation in vivo. Lentiviral GFP-labeled HSCR-ENSCs populated embryonic chick hindgut and postnatal colon of Ednrb(-/-) HSCR, with cells populating the intermuscular layer and forming enteric neurons and glia. Conclusions & Inferences ENSCs can be isolated and cultured from mice with HSCR, and transplanted into the aganglionic bowel of HSCR littermates to generate enteric neuronal networks. These results in an isogenic model establish the potential of using autologous-derived stem cells to treat HSCR and other intestinal neuropathies. C1 [Hotta, R.; Cheng, L. S.; Graham, H. K.; Pan, W.; Nagy, N.; Goldstein, A. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Warren 1153, Boston, MA 02114 USA. [Cheng, L. S.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Pan, W.] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Pediat Surg, Shanghai 200030, Peoples R China. [Nagy, N.] Semmelweis Univ, Dept Human Morphol & Dev Biol, Fac Med, H-1085 Budapest, Hungary. [Belkind-Gerson, J.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Sch Med, Boston, MA 02114 USA. [Belkind-Gerson, J.; Goldstein, A. M.] Massachusetts Gen Hosp, Pediat Neurogastroenterol Program, Boston, MA 02114 USA. RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org FU Massachusetts General Hospital; REACHirschsprung Foundation; Ethicon Scholarship Grant Award from Society of University Surgeons; National Institutes of Health [R01 DK103785] FX RH is supported by grants from the Executive Committee on Research at Massachusetts General Hospital and the REACHirschsprung Foundation. LSC is supported by an Ethicon Scholarship Grant Award from the Society of University Surgeons. AMG is supported by the National Institutes of Health (R01 DK103785). NR 60 TC 4 Z9 4 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD APR PY 2016 VL 28 IS 4 BP 498 EP 512 DI 10.1111/nmo.12744 PG 15 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA DK2VY UT WOS:000374773700004 PM 26685978 ER PT J AU Lefebvre, DR Mandeville, JT Yonekawa, Y Arroyo, JG Torun, N Freitag, SK AF Lefebvre, Daniel R. Mandeville, John T. Yonekawa, Yoshihiro Arroyo, Jorge G. Torun, Nurhan Freitag, Suzanne K. TI A Case Series and Review of Bisphosphonate-associated Orbital Inflammation SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Review DE Bisphosphonate; idiopathic orbital inflammation; orbital inflammation; orbital pseudotumor; zoledronate ID METASTATIC PROSTATE-CANCER; ZOLEDRONIC ACID INFUSION; DISEASE; PAMIDRONATE; SCLERITIS; UVEITIS; ANTERIOR AB Purpose: To report the largest series of new cases to date of bisphosphate-associated orbital inflammation. Methods: A retrospective case review of patients with orbital inflammation following treatment with systemic bisphosphonate. Results: Six patients over an 18-month period (2 males, 4 females) with an average age of 62.2 years had onset of orbital inflammatory symptoms 1-11 days after intravenous bisphosphonate infusion or, in 1 case, 4 weeks after initiation of oral bisphosphonate therapy. Imaging revealed diffuse orbital involvement in 3 cases, isolated lateral rectus muscle involvement in 2 cases, and superior rectus levator involvement in 1 case. Two patients' symptoms resolved spontaneously within 2 weeks, and 3 responded rapidly and completely to corticosteroid therapy. The 1 patient on oral bisphosphonate had a slower but complete response to corticosteroid treatment. Conclusion: Clinicians should be aware of the association between acute orbital inflammation and recent treatment with systemic bisphosphonate medication. C1 [Lefebvre, Daniel R.; Freitag, Suzanne K.] Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg Serv, Boston, MA 02114 USA. [Lefebvre, Daniel R.; Mandeville, John T.; Yonekawa, Yoshihiro; Arroyo, Jorge G.; Torun, Nurhan; Freitag, Suzanne K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Mandeville, John T.] Eye Hlth Serv Inc, Quincy, MA USA. [Arroyo, Jorge G.; Torun, Nurhan] Beth Israel Deaconess Med Ctr, Div Ophthalmol, Boston, MA 02215 USA. RP Lefebvre, DR (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM daniel_lefebvre@meei.harvard.edu NR 23 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0927-3948 EI 1744-5078 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD APR PY 2016 VL 24 IS 2 BP 134 EP 139 DI 10.3109/09273948.2014.942747 PG 6 WC Ophthalmology SC Ophthalmology GA DL0PS UT WOS:000375335600003 PM 25153041 ER PT J AU Papavasileiou, E Prasad, S Freitag, SK Sobrin, L Lobo, AM AF Papavasileiou, Evangelia Prasad, Sashank Freitag, Suzanne K. Sobrin, Lucia Lobo, Ann-Marie TI Ipilimumab-induced Ocular and Orbital Inflammation-A Case Series and Review of the Literature SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Review DE Autoimmune adverse events; CTLA-4 inhibitors; eye and orbit complications; ipilimumab; melanoma ID T-LYMPHOCYTE ANTIGEN-4; METASTATIC MELANOMA; AUTOIMMUNITY; REGRESSION; THERAPY; BLOCKADE; UVEITIS; PATIENT AB Purpose: Ipilimumab, a monoclonal antibody directed against the immune protein cytotoxic T-lymphocyte antigen-4 (CTLA-4), characteristically induces side effects called "immune-related adverse events" (IRAE). Although ophthalmic involvement is rare, we report 7 cases of eye and orbit complications related to ipilimumab therapy. Methods: We performed a retrospective review of patients with metastatic melanoma who developed ipilimumab-related ocular or orbital inflammation who were seen at our institutions. Results: Seven patients were identified: 4 patients had orbital inflammation, 2 had uveitis, and 1 had peripheral ulcerative keratitis. Four patients developed inflammation after the second ipilimumab infusion, 2 after the third infusion and 1 after the first infusion. All 4 patients with orbital inflammation were treated with systemic corticosteroids. Two patients with uveitis were treated with topical steroids, but were also treated with systemic corticosteroids for other IRAE, including colitis and hypophysitis. The patient with keratitis was treated with topical corticosteroids alone with resolution of inflammation. All 7 patients discontinued ipilimumab therapy, 5 due to systemic IRAE and 2 due to tumor progression. Five of 7 patients had tumor progression on ipilimumab therapy. Conclusions: Ocular and orbital inflammation may occur in patients with metastatic melanoma receiving ipilimumab, is frequently accompanied by other IRAEs, and resolves with corticosteroid treatment, often leaving no long-term sequelae. C1 [Papavasileiou, Evangelia; Freitag, Suzanne K.; Sobrin, Lucia; Lobo, Ann-Marie] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. [Prasad, Sashank] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. RP Lobo, AM (reprint author), Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. EM Ann-Marie_Lobo@meei.harvard.edu NR 22 TC 6 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0927-3948 EI 1744-5078 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD APR PY 2016 VL 24 IS 2 BP 140 EP 146 DI 10.3109/09273948.2014.1001858 PG 7 WC Ophthalmology SC Ophthalmology GA DL0PS UT WOS:000375335600004 PM 25760920 ER PT J AU Cho, H Pillai, P Nicholson, L Sobrin, L AF Cho, Heeyoon Pillai, Parvathy Nicholson, Laura Sobrin, Lucia TI Inflammatory Papillitis in Uveitis: Response to Treatment and Use of Optic Nerve Optical Coherence Tomography for Monitoring SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Optical coherence tomography; optic nerve head; papillitis; reproducibility; uveitis ID FIBER LAYER THICKNESS; SPECTRAL-DOMAIN OCT; ANTERIOR UVEITIS; MULTIPLE-SCLEROSIS; MILD PAPILLEDEMA; DISC EDEMA; GLAUCOMA; EYES; AGE AB Purpose: To describe the clinical course of uveitis-associated inflammatory papillitis and evaluate the utility and reproducibility of optic nerve spectral domain optical coherence tomography (SD-OCT). Methods: Data on 22 eyes of 14 patients with uveitis-related papillitis and optic nerve imaging were reviewed. SD-OCT measure reproducibility was determined and parameters were compared in active vs. inactive uveitis. Results: Papillitis resolution lagged behind uveitis resolution in three patients. For SD-OCT measures, the intraclass correlation coefficients were 99.1-100% and 86.9-100% for intraobserver and interobserver reproducibility, respectively. All SD-OCT optic nerve measures except inferior and nasal peripapillary retinal thicknesses were significantly higher in active vs. inactive uveitis after correction for multiple hypotheses testing. Mean optic nerve central thickness decreased from 545.1 to 362.9 Inn (p = 0.01). Conclusions: Resolution of inflammatory papillitis can lag behind resolution of uveitis. SD-OCT assessment of papillitis is reproducible and correlates with presence vs. resolution of uveitis. C1 [Cho, Heeyoon; Pillai, Parvathy; Nicholson, Laura; Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol Uveitis & Retina Serv, 243 Charles St,12th Floor, Boston, MA 02114 USA. [Cho, Heeyoon] Hanyang Univ, Coll Med, Dept Ophthalmol, Seoul 133791, South Korea. RP Sobrin, L (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol Uveitis & Retina Serv, 243 Charles St,12th Floor, Boston, MA 02114 USA. EM lucia_sobrin@meei.harvard.edu FU Massachusetts Lions Eye Research Fund, Abington, MA, USA FX Funding for this study was provided by Massachusetts Lions Eye Research Fund, Abington, MA, USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0927-3948 EI 1744-5078 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD APR PY 2016 VL 24 IS 2 BP 194 EP 206 DI 10.3109/09273948.2014.99104 PG 13 WC Ophthalmology SC Ophthalmology GA DL0PS UT WOS:000375335600012 PM 25549180 ER PT J AU Kohanim, S Palioura, S Saeed, HN Akpek, EK Amescua, G Basu, S Blomquist, PH Bouchard, CS Dart, JK Gai, XW Gomes, JAP Gregory, DG Iyer, G Jacobs, DS Johnson, AJ Kinoshita, S Mantagos, IS Mehta, JS Perez, VL Pflugfelder, SC Sangwan, VS Sippel, KC Sotozono, C Srinivasan, B Tan, DTH Tandon, R Tseng, SCG Ueta, M Chodosh, J AF Kohanim, Sahar Palioura, Sotiria Saeed, Hajirah N. Akpek, Esen K. Amescua, Guillermo Basu, Sayan Blomquist, Preston H. Bouchard, Charles S. Dart, John K. Gai, Xiaowu Gomes, Jose A. P. Gregory, Darren G. Iyer, Geetha Jacobs, Deborah S. Johnson, Anthony J. Kinoshita, Shigeru Mantagos, Iason S. Mehta, Jodhbir S. Perez, Victor L. Pflugfelder, Stephen C. Sangwan, Virender S. Sippel, Kimberly C. Sotozono, Chie Srinivasan, Bhaskar Tan, Donald T. H. Tandon, Radhika Tseng, Scheffer C. G. Ueta, Mayumi Chodosh, James TI Acute and Chronic Ophthalmic Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis - A Comprehensive Review and Guide to Therapy. II. Ophthalmic Disease SO OCULAR SURFACE LA English DT Article DE amniotic membrane transplantation; apoptosis; drug-induced disease; immune-mediated disease; keratinocyte death; keratoprosthesis; ocular surface reconstruction; Stevens-Johnson Syndrome; toxic epidermal necrolysis ID AMNIOTIC MEMBRANE TRANSPLANTATION; OSTEO-ODONTO-KERATOPROSTHESIS; OCULAR SURFACE DISEASE; STEM-CELL DEFICIENCY; BOSTON TYPE-1 KERATOPROSTHESIS; MUCOSAL EPITHELIAL TRANSPLANTATION; TOPICAL RETINOID TREATMENT; DRY-EYE DISORDERS; END-STAGE; ACUTE-PHASE AB Our purpose is to comprehensively review the state of the art with regard to Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. Part I of this review focused on the systemic aspects of SJS/TEN and was published in the January 2016 issue of this journal. The purpose of Part II is to summarize the ocular manifestations and their management through all phases of SJS/TEN, from acute to chronic. We hope this effort will assist ophthalmologists in their management of SJS/TEN, so that patients with this complex and debilitating disease receive the best possible care and experience the most optimal outcomes in their vision and quality of life. C1 [Kohanim, Sahar] Vanderbilt Univ, Sch Med, Vanderbilt Eye Inst, Nashville, TN 37212 USA. [Palioura, Sotiria; Amescua, Guillermo; Perez, Victor L.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Coral Gables, FL 33124 USA. [Saeed, Hajirah N.; Gai, Xiaowu; Jacobs, Deborah S.; Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. [Akpek, Esen K.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21218 USA. [Basu, Sayan] LV Prasad Eye Inst, Hyderabad, Andhra Pradesh, India. [Blomquist, Preston H.] Univ Texas Southwestern Med Ctr, Dallas, TX USA. [Bouchard, Charles S.] Loyola Univ, Chicago, IL 60611 USA. [Dart, John K.] NHS Fdn Trust, Moorfields Eye Hosp, London, England. [Gomes, Jose A. P.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Gregory, Darren G.] Univ Colorado, Sch Med, Rocky Mt Lions Eye Inst, Boulder, CO 80309 USA. [Iyer, Geetha; Srinivasan, Bhaskar] Sankara Nethralaya, Dr G Sitalakshmi Mem Clin Ocular Surface Disorder, Madras, Tamil Nadu, India. [Jacobs, Deborah S.] Boston Fdn Sight, Boston, MA USA. [Johnson, Anthony J.] US Army Inst Surg Res, New York, NY USA. [Kinoshita, Shigeru; Sotozono, Chie; Ueta, Mayumi] Kyoto Prefectural Univ Med, Kyoto 602, Japan. [Mantagos, Iason S.] Harvard Univ, Sch Med, Boston Childrens Hosp, Cambridge, MA 02138 USA. [Mehta, Jodhbir S.; Tan, Donald T. H.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore. [Pflugfelder, Stephen C.] Baylor Coll Med, Cullen Eye Inst, Houston, TX 77030 USA. [Sippel, Kimberly C.] Weill Cornell Med Coll, New York, NY USA. [Tandon, Radhika] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, New Delhi 110029, India. [Tseng, Scheffer C. G.] Ocular Surface Res & Educ Fdn, Ocular Surface Ctr, New York, NY USA. RP Chodosh, J (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM James_Chodosh@meei.harvard.edu FU Research to Prevent Blindness, NY, NY FX Funded in part by an unrestricted grant to the Department of Ophthalmology, Harvard Medical School, Mass. Eye & Ear, from Research to Prevent Blindness, NY, NY. NR 229 TC 5 Z9 5 U1 5 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1542-0124 EI 1937-5913 J9 OCUL SURF JI Ocul. Surf. PD APR PY 2016 VL 14 IS 2 BP 168 EP 188 PG 21 WC Ophthalmology SC Ophthalmology GA DK9AR UT WOS:000375222400010 PM 26882981 ER PT J AU Chao, W Belmonte, C del Castillo, JMB Bron, AJ Dua, HS Nichols, KK Novack, GD Schrader, S Willcox, MD Wolffsohn, JS Sullivan, DA AF Chao, Wendy Belmonte, Carlos del Castillo, Jose M. Benitez Bron, Anthony J. Dua, Harminder S. Nichols, Kelly K. Novack, Gary D. Schrader, Stefan Willcox, Mark D. Wolffsohn, James S. Sullivan, David A. TI Report of the Inaugural Meeting of the TFOS i(2) = initiating innovation Series: Targeting the Unmet Need for Dry Eye Treatment SO OCULAR SURFACE LA English DT Article DE Clinical trials; drug development; dry eye disease (DED); Dry Eye WorkShop II (DEWS II); i(2) = initiating innovation series; Tear Film & Ocular Surface Society ID IN-SITU KERATOMILEUSIS; MEIBOMIAN GLAND DYSFUNCTION; CONTACT-LENS DISCOMFORT; TEAR FILM OSMOLARITY; NERVE GROWTH-FACTOR; CORNEAL EPITHELIAL-CELLS; OCULAR-SURFACE-DISEASE; AUTOLOGOUS SERUM APPLICATION; INTENSE PULSED-LIGHT; HOSPITAL-BASED POPULATION AB On March 21, 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i(2) = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompe. The TFOS i(2) meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i(2) meeting. C1 [Chao, Wendy; Sullivan, David A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. [Belmonte, Carlos] Univ Miguel Hernandez, Inst Neurociencias Alicante, CSIC, Alicante, Spain. [Belmonte, Carlos] Int Brain Res Org, Alicante, Spain. [del Castillo, Jose M. Benitez] Univ Complutense Madrid, Madrid, Spain. [del Castillo, Jose M. Benitez] Hosp Clin San Carlos, Madrid, Spain. [Bron, Anthony J.] Univ Oxford, Oxford, England. [Dua, Harminder S.] Univ Nottingham, Div Clin Neurosci, Sect Ophthalmol, Nottingham NG7 2RD, England. [Nichols, Kelly K.] Univ Alabama Birmingham, Sch Optometry, Birmingham, AL 35294 USA. [Novack, Gary D.] PharmaLog Dev Inc, San Rafael, CA USA. [Schrader, Stefan] Univ Dusseldorf, Lab Expt Ophthalmol, Dusseldorf, Germany. [Willcox, Mark D.] Univ New S Wales, Sch Optometry & Vis Sci, Sydney, NSW, Australia. [Wolffsohn, James S.] Aston Univ, Life & Hlth Sci, Ophthalm Res Grp, Birmingham B4 7ET, W Midlands, England. RP Sullivan, DA (reprint author), Massachusetts Eye & Ear, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM david.sullivan@schepens.harvard.edu OI Chao, Wendy/0000-0002-9418-8723; Wolffsohn, James/0000-0003-4673-8927 FU Dompe (Italy) FX Dompe (Italy) provided unrestricted financial support. Dompe had no role, editorial or otherwise, in the preparation of this manuscript. NR 408 TC 5 Z9 5 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1542-0124 EI 1937-5913 J9 OCUL SURF JI Ocul. Surf. PD APR PY 2016 VL 14 IS 2 BP 264 EP 316 PG 53 WC Ophthalmology SC Ophthalmology GA DK9AR UT WOS:000375222400019 PM 26774910 ER PT J AU Quesnel, AM Ishai, R Cureoglu, S Linthicum, F Lopez, IA Nadol, JB McKenna, MJ AF Quesnel, Alicia M. Ishai, Reuven Cureoglu, Sebahattin Linthicum, Fred Lopez, Ivan A. Nadol, Joseph B., Jr. McKenna, Michael J. TI Lack of Evidence for Nonotosclerotic Stapes Fixation in Human Temporal Bone Histopathology SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Nonotosclerotic stapes fixation; Otosclerosis; Stapedectomy ID MEASLES-VIRUS; OTOSCLEROSIS; EXPRESSION AB Hypothesis:Nonotosclerotic stapes fixation does not represent a significant cause of stapes ankylosis in patients undergoing stapedectomy; the vast majority have otosclerosis.Background:Nonotosclerotic stapes fixation has been proposed as the diagnosis in 30 to 40% of patients undergoing stapedectomy (after excluding rare congenital, systemic, and syndromic causes of stapes fixation and tympanosclerosis). This finding was based on the histopathologic evaluation of total stapedectomy surgical specimens. Since these specimens do not include the surrounding otic capsule, the histopathologic evidence of otosclerosis may be missed.Methods:Human temporal bone specimens from patients who underwent stapes mobilization, stapedotomy, or stapedectomy during life were evaluated for histologic evidence of otosclerosis. Patients with a history of temporal bone trauma, tympanosclerosis, and congenital, systemic, or syndromic causes of stapes fixation were excluded. Therefore, most temporal bone donors carried a clinical diagnosis of otosclerosis.Results:Two hundred ten specimens from three temporal bone collections were independently evaluated. Otosclerosis was found on histology in 99% (207/210). Therefore, the incidence of nonotosclerotic stapes fixation was 1% (3/210). In two of the three patients who did not have otosclerosis, the contralateral temporal bone had otosclerosis on histopathologic evaluation. These patients may have had otosclerosis in the footplate only (which was removed at the time of surgery and not available for review).Conclusion:Nonotosclerotic stapes fixation is not likely a distinct pathologic classification from otosclerosis. Most patients diagnosed with nonotosclerotic stapes fixation likely have otosclerosis, but do not have otosclerotic foci in the stapes itself. C1 [Quesnel, Alicia M.; Ishai, Reuven; Nadol, Joseph B., Jr.; McKenna, Michael J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02115 USA. [Cureoglu, Sebahattin] Univ Minnesota, Dept Otolaryngol, Minneapolis, MN USA. [Linthicum, Fred; Lopez, Ivan A.] Univ Calif Los Angeles, David Geffen Sch Med, Neurotol & House Histol Temporal Bone Lab, Los Angeles, CA 90095 USA. RP McKenna, MJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM michael_mckenna@meei.harvard.edu FU National Institutes of Health (NIH) [U24 DC011943-03] FX This work was supported by a grant from the National Institutes of Health (NIH) U24 DC011943-03. NR 16 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD APR PY 2016 VL 37 IS 4 BP 316 EP 320 DI 10.1097/MAO.0000000000000982 PG 5 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DK4IL UT WOS:000374881000004 PM 26905821 ER PT J AU Ginat, DT Moonis, G AF Ginat, Daniel Thomas Moonis, Gul TI Barotrauma-induced Pneumolabyrinth and Pneumocephalus Associated With Semicircular Canal Dehiscence SO OTOLOGY & NEUROTOLOGY LA English DT Editorial Material C1 [Ginat, Daniel Thomas] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Moonis, Gul] Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. [Moonis, Gul] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Ginat, DT (reprint author), 5841 S Maryland Ave, Chicago, IL 60637 USA. EM ginatd01@gmail.com NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD APR PY 2016 VL 37 IS 4 BP E176 EP E177 DI 10.1097/MAO.0000000000000628 PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DK4IL UT WOS:000374881000002 PM 25275873 ER PT J AU Ouyang, Z Mainali, MK Sinha, N Strack, G Altundal, Y Hao, Y Winningham, TA Sajo, E Celli, J Ngwa, W AF Ouyang, Zi Mainali, Madan Kumar Sinha, Neeharika Strack, Guinevere Altundal, Yucel Hao, Yao Winningham, Thomas Andrew Sajo, Erno Celli, Jonathan Ngwa, Wilfred TI Potential of using cerium oxide nanoparticles for protecting healthy tissue during accelerated partial breast irradiation (APBI) SO PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS LA English DT Article DE APBI; Cerium oxide; Radiolysis; Radioprotectant ID ANTIOXIDANT PROPERTIES; TARGETED RADIOTHERAPY; GOLD NANOPARTICLES; RADIATION; BRACHYTHERAPY; SYSTEM; DAMAGE AB The purpose of this study is to investigate the feasibility of using cerium oxide nanoparticles (CONPs) as radical scavengers during accelerated partial breast irradiation (APBI) to protect normal tissue. We hypothesize that CONPs can be slowly released from the routinely used APBI balloon applicators-via a degradable coating-and protect the normal tissue on the border of the lumpectomy cavity over the duration of APBI. To assess the feasibility of this approach, we analytically calculated the initial concentration of CONPs required to protect normal breast tissue from reactive oxygen species (ROS) and the time required for the particles to diffuse to various distances from the lumpectomy wall. Given that cerium has a high atomic number, we took into account the possible inadvertent dose enhancement that could occur due to the photoelectric interactions with radiotherapy photons. To protect against a typical MammoSite treatment fraction of 3.4 Gy, 5 ng.g (1) of CONPs is required to scavenge hydroxyl radicals and hydrogen peroxide. Using 2 nm sized NPs, with an initial concentration of 1 mg.g (1), we found that 2-10 days of diffusion is required to obtain desired concentrations of CONPs in regions 1-2 cm away from the lumpectomy wall. The resultant dose enhancement factor (DEF) is less than 1.01 under such conditions. Our results predict that CONPs can be employed for radioprotection during APBI using a new design in which balloon applicators are coated with the NPs for sustained/controlled in-situ release from within the lumpectomy cavity. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. C1 [Ouyang, Zi; Strack, Guinevere; Altundal, Yucel; Hao, Yao; Sajo, Erno; Ngwa, Wilfred] Univ Massachusetts, 1 Univ Ave, Lowell, MA 01854 USA. [Mainali, Madan Kumar; Celli, Jonathan] Univ Massachusetts, Boston, MA 02125 USA. [Sinha, Neeharika] Wentworth Inst Technol, Boston, MA USA. [Winningham, Thomas Andrew] Space Coast Canc Ctr, Titusville, FL USA. [Ngwa, Wilfred] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [Ngwa, Wilfred] Harvard Univ, Sch Med, Boston, MA USA. RP Ouyang, Z (reprint author), Univ Massachusetts, Dept Phys & Appl Phys, 1 Univ Ave, Lowell, MA 01854 USA. EM Zi_Ouyang@student.uml.edu FU NCI NIH HHS [R00 CA155045, K01 CA172478] NR 30 TC 2 Z9 4 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1120-1797 EI 1724-191X J9 PHYS MEDICA JI Phys. Medica PD APR PY 2016 VL 32 IS 4 BP 631 EP 635 DI 10.1016/j.ejmp.2016.03.014 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DK7SK UT WOS:000375125800014 PM 27053452 ER PT J AU Islam, K Abu Sayeed, M Hossen, E Khanam, F Charles, RC Andrews, J Ryan, ET Qadri, F AF Islam, Kamrul Abu Sayeed, Md. Hossen, Emran Khanam, Farhana Charles, Richelle C. Andrews, Jason Ryan, Edward T. Qadri, Firdausi TI Comparison of the Performance of the TPTest, Tubex, Typhidot and Widal Immunodiagnostic Assays and Blood Cultures in Detecting Patients with Typhoid Fever in Bangladesh, Including Using a Bayesian Latent Class Modeling Approach SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID DIAGNOSTIC-TESTS; ENTERIC FEVER; GOLD STANDARD; CHILDREN; ANTIBODIES; IGM AB Background There is an urgent need for an improved diagnostic assay for typhoid fever. In this current study, we compared the recently developed TPTest (Typhoid and Paratyphoid Test) with the Widal test, blood culture, and two commonly used commercially available kits, Tubex and Typhidot. Methodology For analysis, we categorized 92 Bangladeshi patients with suspected enteric fever into four groups: S. Typhi bacteremic patients (n = 28); patients with a fourfold change in Widal test from day 0 to convalescent period (n = 7); patients with Widal titer >= 1:320 (n = 13) at either acute or convalescent stage of disease; and patients suspected with enteric fever, but with a negative blood culture and Widal titer (n = 44). We also tested healthy endemic zone controls (n = 20) and Bangladeshi patients with other febrile illnesses (n = 15). Sample size was based on convenience to facilitate preliminary analysis. Principle findings Of 28 S. Typhi bacteremic patients, 28 (100%), 21 (75%) and 18 (64%) patients were positive by TPTest, Tubex and Typhidot, respectively. In healthy endemic zone controls, the TPTest method was negative in all, whereas Tubex and Typhidot were positive in 3 (15%) and 5 (25%), respectively. We then estimated sensitivity and specificity of all diagnostic tests using Bayesian latent class modeling. The sensitivity of TPTest, Tubex and Typhidot were estimated at 96.0% (95% CI: 87.1%-99.8%), 60.2% (95% CI: 49.3%-71.2%), and 59.6% (95% CI: 50.1%-69.3%), respectively. Specificity was estimated at 96.6%(90.7%-99.2%) for TPTest, 89.9% (79.6%-96.8%) for Tubex, and 80.0% (67.7%-89.7%) for Typhidot. Conclusion These results suggest that the TPTest is highly sensitive and specific in diagnosing individuals with typhoid fever in a typhoid endemic setting, outperforming currently available and commonly used alternatives. C1 [Islam, Kamrul; Abu Sayeed, Md.; Hossen, Emran; Khanam, Farhana; Qadri, Firdausi] Icddr b, Ctr Vaccine Sci, Dhaka, Bangladesh. [Charles, Richelle C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charles, Richelle C.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Andrews, Jason] Stanford Univ, Sch Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. RP Qadri, F (reprint author), Icddr b, Ctr Vaccine Sci, Dhaka, Bangladesh. EM fqadri@icddrb.org FU icddr,b; National Institutes of Health; National Institute of Allergy and Infectious Diseases [AI100023]; Fogarty International Center Training Grant in Vaccine Development and Public Health [D43 TW 005572]; Swedish International Development Cooperation Agency; Government of Bangladesh; Government of Canada; Government of Sweden; Government of UK FX This study was supported by icddr,b and the grants from National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI100023 [ETR, FQ]) as well as a Fogarty International Center Training Grant in Vaccine Development and Public Health (D43 TW 005572 [KI, MAS, FK]), and the Swedish International Development Cooperation Agency (FQ). icddr,b is grateful to the Government of Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 1 Z9 1 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD APR PY 2016 VL 10 IS 4 AR e0004558 DI 10.1371/journal.pntd.0004558 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DL1FC UT WOS:000375376700022 PM 27058877 ER PT J AU Brown, JR AF Brown, Jennifer R. TI The PI3K pathway: clinical inhibition in chronic lymphocytic leukemia SO SEMINARS IN ONCOLOGY LA English DT Review DE CLL; PI3K; B-cell receptor; Idelalisib; Duvelisib; TGR-1202 ID B-CELL MALIGNANCIES; PHOSPHATIDYLINOSITOL 3-KINASE-DELTA; PHOSPHOINOSITIDE 3-KINASES; P110 DELTA; IDELALISIB; P110-DELTA; CAL-101; LEUKOCYTES; LYMPHOMA; CANCER AB Constitutive or mutational activation of the phosphatidylinositol 3 kinase, or PI3K, has been implicated in many cancers, including chronic lymphocytic leukemia (CLL). The delta isoform of the p110 catalytic subunit of PI3K has its primary physiologic function in B cells and appears to be the predominant mediator of most PI3K signals in CLL cells. Idelalisib is a first-in-class inhibitor of the PI3K delta isoform that shows near complete inhibition of AKT phosphorylation in CLL cells in vitro and in vivo. Idelalisib shows the classic pattern of response to BCR inhibition in CLL, with rapid nodal response and transient increase in lymphocytosis. The phase I study established the recommended dose as 150 mg twice per day. Subsequent registration trials have focused predominantly on antibody combinations, leading to the US Food and Drug Administration (FDA) approval of idelalisib with rituximab for relapsed CLL patients for whom rituximab is appropriate therapy in summer 2014. The median progression-free survival (PFS) of idelalisib-rituximab in this heavily pretreated CLL population with multiple comorbidities and frequent 17p deletion was an impressive 19.4 months. The success of idelalisib has paved the way for the development of other PI3K inhibitors in CLL, including duvelisib and TGR-1202, which are in or moving toward registration trials. (C) 2016 Elsevier Inc. All rights reserved. C1 [Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, CLL Ctr, Boston, MA 02215 USA. [Brown, Jennifer R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jbrown2@partners.org FU Gilead FX J.R.B. has served as a consultant for Gilead and Infinity, and received research funding from Gilead. NR 35 TC 7 Z9 8 U1 3 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2016 VL 43 IS 2 BP 260 EP 264 DI 10.1053/j.seminoncol.2016.02.004 PG 5 WC Oncology SC Oncology GA DK8IP UT WOS:000375170700009 PM 27040704 ER PT J AU Fraietta, JA Schwab, RD Maus, MV AF Fraietta, Joseph A. Schwab, Robert D. Maus, Marcela V. TI Improving therapy of chronic lymphocytic leukemia with chimeric antigen receptor T cells SO SEMINARS IN ONCOLOGY LA English DT Review DE CAR; CLL; Immunotherapy; T cell; Leukemia ID ACUTE MYELOID-LEUKEMIA; VERSUS-HOST-DISEASE; GROWTH-FACTOR-BETA; MEMORY STEM-CELLS; B-CELLS; ADOPTIVE TRANSFER; IN-VIVO; ANTITUMOR IMMUNITY; DENDRITIC CELLS; COSTIMULATORY MOLECULES AB Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and redirecting the immune system against cancer. This review will briefly summarize T-cell therapies in development for CLL disease. We discuss the role of T-cell function and phenotype, T-cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL. (C) 2016 Elsevier Inc. All rights reserved. C1 [Fraietta, Joseph A.; Schwab, Robert D.] Univ Penn, Ctr Cellular Immunotherapy, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Maus, Marcela V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cellular Immunotherapy Program, Boston, MA USA. RP Maus, MV (reprint author), Bldg 149,Thirteenth St,Room 7-219, Charlestown, MA 02129 USA. EM mvmaus@mgh.harvard.edu FU NCI NIH HHS [K08 CA166039] NR 123 TC 1 Z9 1 U1 6 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2016 VL 43 IS 2 BP 291 EP 299 DI 10.1053/j.seminoncol.2016.02.006 PG 9 WC Oncology SC Oncology GA DK8IP UT WOS:000375170700013 PM 27040708 ER PT J AU Lee, LY Foley, DP AF Lee, Lung-Yi Foley, David P. TI Technical Aspects of Orthotopic Liver Transplantation for Hepatocellular Carcinoma SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Liver transplantation; Surgery; Hepatocellular carcinoma; Piggyback technique; Portal vein thrombosis ID TRANSARTERIAL CHEMOEMBOLIZATION; BILIARY COMPLICATIONS; CANCER STATISTICS; HEPATIC-ARTERY; SURVIVAL; EXPERIENCE; CIRRHOSIS AB Hepatocellular carcinoma (HCC) remains a significant malignancy and is the second leading cause of cancer death worldwide. Multiple therapeutic strategies exist for patients with HCC including locoregional therapy, liver resection, and liver transplantation. In many instances locoregional therapy is used to decrease tumor burden and "bridge" patients to liver transplant. Surgical technique during liver transplantation may need to be altered in light of these preoperative therapies used for treating HCC. In this review, we discuss the technical aspects of liver transplantation and how they are impacted in patients with HCC. C1 [Lee, Lung-Yi; Foley, David P.] Univ Wisconsin, Dept Surg, Ctr Clin Sci, Sch Med & Publ Hlth, H4-766,600 Highland Ave, Madison, WI 53792 USA. [Foley, David P.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, 2500 Overlook Terrace, Madison, WI 53705 USA. RP Foley, DP (reprint author), Univ Wisconsin, Ctr Clin Sci, H4-766,600 Highland Ave, Madison, WI 53792 USA. EM foley@surgery.wisc.edu NR 28 TC 0 Z9 0 U1 4 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD APR PY 2016 VL 96 IS 2 BP 269 EP + DI 10.1016/j.suc.2015.11.004 PG 15 WC Surgery SC Surgery GA DK6GR UT WOS:000375021200011 PM 27017864 ER PT J AU Wintner, A Kim, MM Bechis, SK Kreydin, EI AF Wintner, Anton Kim, Michelle M. Bechis, Seth K. Kreydin, Evgeniy I. TI Voiding Dysfunction in Multiple Sclerosis SO SEMINARS IN NEUROLOGY LA English DT Article DE neurogenic bladder; voiding dysfunction; multiple sclerosis ID DETRUSOR-SPHINCTER DYSSYNERGIA; URINARY-TRACT DYSFUNCTION; SPINAL-CORD-INJURY; QUALITY-OF-LIFE; BLADDER DYSFUNCTION; SUPRASPINAL CONTROL; URODYNAMIC FINDINGS; OVERACTIVE BLADDER; ECONOMIC-IMPACT; MANAGEMENT AB Voiding dysfunction is a common and debilitating consequence of multiple sclerosis (MS). The prevalence and severity of voiding dysfunction increases with the increasing severity of MS, but even the mildest forms of the disease are associated with urinary symptoms in 30% of patients. Every component of the central nervous system is involved in regulating voiding; as a result, MS can lead to a wide variety of urinary symptoms and urologic complications. The effect of MS on voiding can be classified according to the resulting function of the bladder and the urethral sphincter during storage and emptying of urine. Therapy is targeted to the specific bladder and sphincter abnormalities that occur. The, primary goals of therapy are prevention of injury to the upper urinary tract (kidneys), reduction in urinary tract infections, and maintenance of urinary continence. These goals can be achieved by interventions ranging from behavioral modification to major reconstructive surgery. C1 [Wintner, Anton; Kim, Michelle M.; Bechis, Seth K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Kreydin, Evgeniy I.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, 300 Stein Plaza,3rd Floor, Los Angeles, CA 90095 USA. RP Kreydin, EI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, 300 Stein Plaza,3rd Floor, Los Angeles, CA 90095 USA. EM ekreydin@mednet.ucla.edu NR 45 TC 0 Z9 0 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 EI 1098-9021 J9 SEMIN NEUROL JI Semin. Neurol. PD APR PY 2016 VL 36 IS 2 BP 212 EP 218 DI 10.1055/s-0035-1571212 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DK0QN UT WOS:000374617400014 ER PT J AU Duan, Q Mao, XX Xiao, Y Liu, ZZ Wang, YG Zhou, HY Zhou, ZX Cai, JX Xia, K Zhu, QB Qi, J Huang, H Plutzky, J Yang, TL AF Duan, Qiong Mao, Xiaoxiao Xiao, Yi Liu, Zhenzhen Wang, Yangui Zhou, Haoyang Zhou, Zhengxiang Cai, Jinxing Xia, Ke Zhu, Qubo Qi, Jun Huang, He Plutzky, Jorge Yang, Tianlun TI Super enhancers at the miR-146a and miR-155 genes contribute to self-regulation of inflammation SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Article DE NF-kappa B; BET bromodomain; microRNA; Inflammation; Super enhancer ID NF-KAPPA-B; BROMODOMAIN PROTEIN BRD4; RNA-POLYMERASE-II; TRANSCRIPTIONAL ELONGATION; SELECTIVE-INHIBITION; MICRORNA BIOGENESIS; CELL IDENTITY; P-TEFB; DISEASE; ATHEROSCLEROSIS AB Inflammatory response is essential to host defense and repair, and requires tight regulation as excessive and constant inflammatory response is deleterious. We recently identified that one of the general but key mechanisms for inflammatory gene transcription regulation is controlled by the formation of super enhancers mediated by NF-kappa B, and bromodomain and extraterminal (BET) proteins. Given that microRNA transcription shares a similar mechanism to mRNA, we assume that the inflammatory microRNAs transcription could be NF-kappa B and BET bromodomain dependent. In the present study, we confirmed that inflammatory stimuli changed human umbilical vein endothelial cells (HUVEC) microRNA profile. Among these microRNAs, miR-146a and miR-155, two well-established inflammatory microRNAs, are both down-regulated at transcriptional level by NF-kappa B and BET bromodomain inhibition. To pursue this mechanism, we analyzed the ChIP-seq data and found that NF-kappa B, BRD4 and RNA POL II were rapidly distributed at the upstream regions of miR-146a and miR-155, and more importantly mediated the formation of the super enhancers that drive miR-146a and miR-155 transcription. These microRNAs transcription driven by super enhancers in turn downregulate both in vitro and in vivo canonical inflammatory genes expression through targeting inflammatory mediators. This novel finding demonstrated how the host self-regulates inflammatory genes expression at both transcriptional and post-transcriptional level to ensure the appropriate level of the host inflammatory response. (C) 2016 Elsevier B.V. All rights reserved. C1 [Duan, Qiong; Mao, Xiaoxiao; Xiao, Yi; Liu, Zhenzhen; Wang, Yangui; Zhou, Haoyang; Zhou, Zhengxiang; Xia, Ke; Yang, Tianlun] Cent S Univ, Xiangya Hosp, Cardiovasc Div, Changsha, Hunan, Peoples R China. [Mao, Xiaoxiao; Plutzky, Jorge] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Wang, Yangui] Peoples Hosp Hunan Prov, Dept Gerontol, Changsha, Hunan, Peoples R China. [Cai, Jinxing; Huang, He] Cent S Univ, Xiangya Sch Med, Dept Histol & Embryol, 172 Tongzipo Rd, Changsha, Hunan, Peoples R China. [Zhu, Qubo] Cent S Univ, Sch Pharmaceut Sci, Dept Pharm, 172 Tongzipo Rd, Changsha, Hunan, Peoples R China. [Qi, Jun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RP Yang, TL (reprint author), Cent S Univ, Xiangya Hosp, Cardiovasc Div, Changsha, Hunan, Peoples R China.; Plutzky, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. EM jplutzky@rics.bwh.harvard.edu; tianluny@163.com FU National Natural Science Foundation of China [81370320, 81241009]; Xiangya Eminent Doctor Project [013]; NIH/NHLBI [1R56HL125894-01]; Zijing Foundation [2014-0016] FX This work was supported by National Natural Science Foundation of China 81370320, 81241009 (TL Yang), Xiangya Eminent Doctor Project #013 (TL Yang) NIH/NHLBI 1R56HL125894-01 (JP) and Zijing Foundation 2014-0016 (Q Duan). NR 33 TC 3 Z9 5 U1 5 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 EI 0006-3002 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD APR PY 2016 VL 1859 IS 4 BP 564 EP 571 DI 10.1016/j.bbagrm.2016.02.004 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DJ7CW UT WOS:000374370500003 PM 26855180 ER PT J AU Papakostas, TD Jakobiec, FA Stagner, AM Vavvas, D AF Papakostas, Thanos D. Jakobiec, Frederick A. Stagner, Anna M. Vavvas, Demetrios TI Unusual focal remnant of the tunica vasculosa lentis SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Letter ID PERSISTENT PUPILLARY MEMBRANE C1 [Papakostas, Thanos D.; Vavvas, Demetrios] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Retina Serv, Boston, MA USA. [Jakobiec, Frederick A.; Stagner, Anna M.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA USA. RP Papakostas, TD (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Retina Serv, Boston, MA USA. NR 5 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1442-6404 EI 1442-9071 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD APR PY 2016 VL 44 IS 3 BP 203 EP 205 DI 10.1111/ceo.12642 PG 3 WC Ophthalmology SC Ophthalmology GA DK1WS UT WOS:000374706400011 PM 26348530 ER PT J AU Musher, DM AF Musher, Daniel M. TI Quantitative Molecular Approach to Diagnosing Pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE community-acquired pneumonia; etiology; sputum; Gram stain ID COMMUNITY-ACQUIRED PNEUMONIA; ADULTS C1 [Musher, Daniel M.] Baylor Coll Med, Houston, TX 77030 USA. [Musher, Daniel M.] Michael E DeBakey VA Med Ctr, Infect Dis Sect, Med Care Line, Houston, TX USA. RP Musher, DM (reprint author), VA Med Ctr, 2002 Holcombe, Houston, TX 77030 USA. EM daniel.musher@va.gov NR 11 TC 3 Z9 3 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2016 VL 62 IS 7 BP 824 EP 825 DI 10.1093/cid/civ1216 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DJ5LD UT WOS:000374248700002 PM 26747824 ER PT J AU Fox, GJ Mitnick, CD Benedetti, A Chan, ED Becerra, M Chiang, CY Keshavjee, S Koh, WJ Shiraishi, Y Viiklepp, P Yim, JJ Pasvol, G Robert, J Shim, TS Shin, SS Menzies, D AF Fox, Gregory J. Mitnick, Carole D. Benedetti, Andrea Chan, Edward D. Becerra, Mercedes Chiang, Chen-Yuan Keshavjee, Salmaan Koh, Won-Jung Shiraishi, Yuji Viiklepp, Piret Yim, Jae-Joon Pasvol, Geoffrey Robert, Jerome Shim, Tae Sun Shin, Sonya S. Menzies, Dick CA Collaborative Grp Meta-Anal Indivi TI Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE multidrug resistant tuberculosis; thoracic surgery; pneumonectomy; metaanalysis; individual patient data ID TREATMENT OUTCOMES AB Background. Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. Methods. Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. Results. A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I-R(2), 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI,.6-2.3; I-R(2), 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I-R(2), 0.2%). Conclusions. Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy. C1 [Fox, Gregory J.; Benedetti, Andrea; Menzies, Dick] McGill Univ, Montreal Chest Inst, Montreal, PQ H3A 2T5, Canada. [Mitnick, Carole D.; Becerra, Mercedes; Keshavjee, Salmaan] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Acad Affairs, Denver, CO USA. [Chiang, Chen-Yuan] Taipei Med Univ, Wan Fang Hosp, Taipei, Taiwan. [Koh, Won-Jung] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Shiraishi, Yuji] Fukujuji Hosp, Sect Chest Surg, Tokyo, Japan. [Viiklepp, Piret] Natl Inst Hlth Dev, Estonian TB Registry, Tallinn, Estonia. [Yim, Jae-Joon] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Pasvol, Geoffrey] Univ London Imperial Coll Sci Technol & Med, Dept Infect & Trop Med, London, England. [Robert, Jerome] Univ Paris 06, Lab Bacteriol Hyg, Paris, France. [Shim, Tae Sun] Univ Ulsan, Coll Med, Dept Pulm & Crit Care Med, Asan Med Ctr, Seoul, South Korea. [Shin, Sonya S.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. RP Menzies, D (reprint author), 2155 Guy St, Montreal, PQ H3H 2R9, Canada. EM dick.menzies@mcgill.ca RI Koh, Won Jung/C-9595-2011; OI Hollm-Delgado, Maria-Graciela/0000-0003-1067-8520; ROBERT, JEROME/0000-0002-9380-0570 FU CJ Martin post-doctoral fellowship [APP1054107]; Australian National Health and Medical Research Council FX This work was supported by a CJ Martin post-doctoral fellowship (APP1054107) to G. J. F. from the Australian National Health and Medical Research Council. NR 17 TC 5 Z9 5 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2016 VL 62 IS 7 BP 887 EP 895 DI 10.1093/cid/ciw002 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DJ5LD UT WOS:000374248700011 PM 26757804 ER PT J AU Walensky, RP Horn, TH Paltiel, AD AF Walensky, Rochelle P. Horn, Tim H. Paltiel, A. David TI The Epi-TAF for Tenofovir Disoproxil Fumarate? SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE tenofovir disoproxil fumarate; tenofovir alafenamide; costs; cost-effectiveness; generics AB Approximately 84% of human immunodeficiency virus (HIV)-infected US residents on antiretroviral therapy currently receive some form of tenofovir disoproxil fumarate (TDF) as part of their HIV treatment regimen. The TDF analogue tenofovir alafenamide (TAF) has demonstrated equal efficacy but with decreased renal injury and bone mineral density loss compared with TDF. We examine how much more society ought to be willing to pay for TAF over TDF, in exchange for its improved toxicity profile. Using cost-effectiveness methods, we find that current conditions warrant an annual premium of up to $1000 over the average wholesale price (AWP) of TDF. Once generic coformulations of tenofovir/lamivudine become accessible, however, the appropriate premium for TAF will likely merit a downward adjustment, using generic TDF-based costs as the benchmark. C1 [Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, 50 Staniford St,9th Flr, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Harvard Univ, Ctr AIDS Res, Sch Med, Boston, MA 02115 USA. [Horn, Tim H.] Treatment Act Grp, New York, NY USA. [Paltiel, A. David] Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, 50 Staniford St,9th Flr, Boston, MA 02114 USA. EM rwalensky@partners.org NR 19 TC 2 Z9 2 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2016 VL 62 IS 7 BP 915 EP 918 DI 10.1093/cid/civ1000 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DJ5LD UT WOS:000374248700016 PM 26658300 ER PT J AU Ovchinnikova, ES Schmitter, D Vegter, EL ter Maaten, JM Valente, MAE Liu, LCY van der Harst, P Pinto, YM de Boer, RA Meyer, S Teerlink, JR O'Connor, CM Metra, M Davison, BA Bloomfield, DM Cotter, G Cleland, JG Mebazaa, A Laribi, S Givertz, MM Ponikowski, P van der Meer, P van Veldhuisen, DJ Voors, AA Berezikov, E AF Ovchinnikova, Ekaterina S. Schmitter, Daniela Vegter, Eline L. ter Maaten, Jozine M. Valente, Mattia A. E. Liu, Licette C. Y. van der Harst, Pim Pinto, Yigal M. de Boer, Rudolf A. Meyer, Sven Teerlink, John R. O'Connor, Christopher M. Metra, Marco Davison, Beth A. Bloomfield, Daniel M. Cotter, Gadi Cleland, John G. Mebazaa, Alexandre Laribi, Said Givertz, Michael M. Ponikowski, Piotr van der Meer, Peter van Veldhuisen, Dirk J. Voors, Adriaan A. Berezikov, Eugene TI Signature of circulating microRNAs in patients with acute heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Circulating microRNAs; Biomarkers ID DILATED CARDIOMYOPATHY; EJECTION FRACTION; CANDIDATE MARKERS; HYPERTROPHY; EXPRESSION; MIRNAS; BIOMARKERS; CARDIOMYOCYTES; MECHANISM; DIAGNOSIS AB AimsOur aim was to identify circulating microRNAs (miRNAs) associated with acute heart failure (AHF). Methods and resultsPlasma miRNA profiling included 137 patients with AHF from 3 different cohorts, 20 with chronic heart failure (CHF), 8 with acute exacerbation of COPD, and 41 healthy controls. Levels of circulating miRNAs were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Plasma levels of miRNAs in patients with AHF were decreased compared with CHF patients or healthy subjects, whereas no significant changes were observed between acute COPD patients and controls. Fifteen miRNAs found in the discovery phase to differ most significantly between healthy controls and patients with AHF were further investigated in an extended cohort of 100 AHF patients at admission and a separate cohort of 18 AHF patients at different time points. Out of these 15 miRNAs, 12 could be confirmed in an additional AHF validation cohort and 7 passed the Bonferroni correction threshold (miR-18a-5p, miR-26b-5p, miR-27a-3p, miR-30e-5p, miR-106a-5p, miR-199a-3p, and miR-652-3p, all P < 0.00005). A further drop in miRNA levels within 48 h after AHF admission was associated with an increased risk of 180-day mortality in a subset of the identified miRNAs. ConclusionsDeclining levels of circulating miRNAs were associated with increasing acuity of heart failure. Early in-hospital decreasing miRNA levels were predictive for mortality in a subset of miRNAs in patients with AHF. The discovered miRNA panel may serve as a launch-pad for molecular pathway studies to identify new pharmacological targets and miRNA-based therapies. C1 [Ovchinnikova, Ekaterina S.; Vegter, Eline L.; ter Maaten, Jozine M.; Valente, Mattia A. E.; Liu, Licette C. Y.; van der Harst, Pim; de Boer, Rudolf A.; Meyer, Sven; van der Meer, Peter; van Veldhuisen, Dirk J.; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, AB31,Hanzepl 1, NL-9713 GZ Groningen, Netherlands. [Ovchinnikova, Ekaterina S.; Berezikov, Eugene] Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Ageing, Groningen, Netherlands. [Schmitter, Daniela] Momentum Res Inc, Allschwil, Switzerland. [Pinto, Yigal M.] Univ Amsterdam, Amsterdam, Netherlands. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Metra, Marco] Univ Brescia, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, Cardiol, Brescia, Italy. [Davison, Beth A.; Cotter, Gadi] Momentum Res, Durham, NC USA. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Cleland, John G.] Univ London Imperial Coll Sci Technol & Med, Royal Brompton & Harefield Hosp, Natl Heart & Lung Inst, London, England. [Mebazaa, Alexandre] Univ Paris Diderot, St Louis Lariboisiere Univ Hosp, AP HP,INSERM,U942, Dept Anesthesiol & Crit Care, Paris, France. [Mebazaa, Alexandre] Univ Paris Diderot, St Louis Lariboisiere Univ Hosp, AP HP,INSERM,U942, Burn Unit, Paris, France. [Laribi, Said] St Louis Lariboisiere Univ Hosp, AP HP, INSERM,U942, Dept Emergency Med, Paris, France. [Givertz, Michael M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. RP Voors, AA (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, AB31,Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM a.a.voors@umcg.nl RI Laribi, said/S-3693-2016; Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Berezikov, Eugene/0000-0002-1145-2884; Cleland, John/0000-0002-1471-7016 FU Dutch Heart Foundation: Approaching Heart Failure By Translational Research of RNA Mechanisms (ARENA); NovaCardia, a subsidiary of Merck; Netherlands Heart Foundation [2000Z003]; Biosite France SAS; Jouy-en-Josas, France (BNP); Roche Diagnostics Nederland BV, Venlo, The Netherlands (NT-proBNP); Novartis Pharma BV, Arnhem, The Netherlands FX This study was supported by a Grant from the Dutch Heart Foundation: Approaching Heart Failure By Translational Research of RNA Mechanisms (ARENA). The PROTECT trial was supported by NovaCardia, a subsidiary of Merck. COACH was supported by grant 2000Z003 from the Netherlands Heart Foundation and by additional unrestricted grants from Biosite France SAS, Jouy-en-Josas, France (BNP), Roche Diagnostics Nederland BV, Venlo, The Netherlands (NT-proBNP), and Novartis Pharma BV, Arnhem, The Netherlands. NR 44 TC 13 Z9 13 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD APR PY 2016 VL 18 IS 4 BP 414 EP 423 DI 10.1002/ejhf.332 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DJ6GK UT WOS:000374308700012 PM 26345695 ER PT J AU Samsky, MD Dunning, A DeVore, AD Schulte, PJ Starling, RC Tang, WHW Armstrong, PW Ezekowitz, JA Butler, J McMurray, JJ Teerlink, JR Voors, AA Metra, M Mentz, RJ O'Connor, CM Patel, CB Hernandez, AF AF Samsky, Marc D. Dunning, Allison DeVore, Adam D. Schulte, Phillip J. Starling, Randall C. Tang, W. H. Wilson Armstrong, Paul W. Ezekowitz, Justin A. Butler, Javed McMurray, John J. Teerlink, John R. Voors, Adrian A. Metra, Marco Mentz, Robert J. O'Connor, Christopher M. Patel, Chetan B. Hernandez, Adrian F. TI Liver function tests in patients with acute heart failure and associated outcomes: insights from ASCEND-HF SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Liver function tests; Outcomes ID FUNCTION ABNORMALITIES; PROGNOSTIC-SIGNIFICANCE; HYPOXIC HEPATITIS; VENOUS-PRESSURE; RENAL-FUNCTION; TASK-FORCE; DYSFUNCTION; PREVALENCE; CONGESTION; GUIDELINES AB AimsWe aimed to characterize abnormal liver function tests in patients with heart failure (HF), as they are commonly encountered yet poorly defined. Methods and resultsWe used data from ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) to characterize associations with baseline liver function tests (LFTs). Each LFT was analysed as both a continuous and dichotomous variable [normal vs. abnormal; bilirubin >1.0mg/dL; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >35mmol/L]. Logistic regression assessed the association of LFTs and 30-day all-cause mortality and HF rehospitalization, and Cox proportional hazards assessed the association with 180-day all-cause mortality among patients alive at a 30-day landmark. In ASCEND-HF, 4228 (59%) had complete admission LFT data. Of these, 42% had abnormal bilirubin, 22% had abnormal ALT, and 30% had abnormal AST. Patients with abnormal LFTs were younger, had lower body mass index, and lower left ventricular ejection fraction. In multivariable models, increased total bilirubin was associated with increased 30-day mortality or HF rehospitalization [hazard ratio (HR) 1.17 per 1mg/dL increase, 95% confidence interval (CI) 1.04, 1.32; P=0.012], but not with an increase in 180-day mortality (HR 1.10, 95% CI 0.97, 1.25; P=0.13) per 1mg/dl increase. Compared with normal bilirubin levels, abnormal bilirubin was associated with increased 30-day mortality or HF rehospitalization (HR 1.24, 95% CI 1.00, 1.54; P=0.048) and 180-day mortality (HR 1.32, 95% CI 1.08, 1.62; P=0.007). We found no association with AST or ALT and outcomes. ConclusionGreater than 40% of patients hospitalized with acute HF had abnormal LFTs. After multivariable adjustment, only elevated bilirubin was independently associated with worse clinical outcomes and may represent an important prognostic variable. C1 [Samsky, Marc D.; DeVore, Adam D.; Mentz, Robert J.; O'Connor, Christopher M.; Patel, Chetan B.; Hernandez, Adrian F.] Duke Univ, Durham, NC USA. [Dunning, Allison; DeVore, Adam D.; Schulte, Phillip J.; Mentz, Robert J.; O'Connor, Christopher M.; Patel, Chetan B.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Starling, Randall C.; Tang, W. H. Wilson] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Armstrong, Paul W.] Canadian VIGOUR Ctr, Edmonton, AB, Canada. [Armstrong, Paul W.; Ezekowitz, Justin A.] Univ Alberta, Edmonton, AB, Canada. [Butler, Javed] Stony Brook Univ Hosp, Stony Brook, NY USA. [McMurray, John J.] Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [McMurray, John J.] Univ Glasgow, Glasgow, Lanark, Scotland. [Teerlink, John R.] Univ Calif San Francisco, San Francisco VA Hosp, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Voors, Adrian A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Metra, Marco] Univ Brescia, Brescia, Italy. RP Samsky, MD (reprint author), Duke Univ, Med Ctr, Duke North Hosp, Room 8254,2301 Erwin Rd, Durham, NC 27710 USA. EM marc.samsky@dm.duke.edu OI DeVore, Adam/0000-0002-4679-2221; mcmurray, john/0000-0002-6317-3975 FU Johnson and Johnson FX The ASCEND-HF trial was supported by Johnson and Johnson. NR 36 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD APR PY 2016 VL 18 IS 4 BP 424 EP 432 DI 10.1002/ejhf.440 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DJ6GK UT WOS:000374308700013 PM 26707029 ER PT J AU Gianni, C Di Biase, L Mohanty, S Trivedi, C Bai, R Al-Ahmad, A Burkhardt, JD Gallinghouse, GJ Horton, RP Sanchez, JE Hranitzky, PM Lakkireddy, D Mansour, MC Santangeli, P Zado, ES Marchlinski, FE Beheiry, S Hao, SC Couts, L Gibson, D Natale, A AF Gianni, Carola Di Biase, Luigi Mohanty, Sanghamitra Trivedi, Chintan Bai, Rong Al-Ahmad, Amin Burkhardt, J. David Gallinghouse, G. Joseph Horton, Rodney P. Sanchez, Javier E. Hranitzky, Patrick M. Lakkireddy, Dhanunjaya Mansour, Moussa C. Santangeli, Pasquale Zado, Erica S. Marchlinski, Francis E. Beheiry, Salwa Hao, Steven C. Couts, Linda Gibson, Douglas Natale, Andrea TI Management of Periprocedural and Early Pericardial Effusions With Tamponade Following Ablation of Atrial Fibrillation With Uninterrupted Factor Xa Inhibitors: A Case Series SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE 4-factor prothrombin complex concentrate; apixaban; atrial fibrillation ablation; factor Xa inhibitors; pericardial tamponade; rivaroxaban; uninterrupted anticoagulation ID PROTHROMBIN COMPLEX CONCENTRATE; CATHETER ABLATION; RADIOFREQUENCY ABLATION; CARDIAC PERFORATION; RIVAROXABAN; SAFETY; ANTICOAGULATION; APIXABAN; REVERSAL; WARFARIN AB Management of Tamponade Following AF Ablation With FXaI. Introduction: Because of the absence of a dedicated reversal agent, the outcome of pericardial effusion (PE) following procedures performed with uninterrupted apixaban or rivaroxaban is unknown. We report the characteristics of PEs presenting with tamponade in patients undergoing AF ablation with uninterrupted factor Xa inhibition (FXaI) to understand their management and prognosis. Methods and Results: We performed a multicenter cross-sectional survey in 10 centers across the United States. Patient data were obtained by chart review. In all patients the procedure was performed with uninterrupted FXaI. A total of 16 PEs requiring intervention were reported from 5 centers. Two patients were on apixaban 5 mg BD, the remaining on rivaroxaban 20 mg OD. Eleven PEs occurred in the periprocedural setting, and 5 PEs occurred from 1 to 28 days after the procedure. Pericardiocentesis and drainage were performed in all cases. Protamine and 4-factor prothrombin complex concentrate (4F-PCC) were given in all periprocedural cases. Two patients required surgery: in one case coagulation of the pericardial blood prevented effective drainage, and in the other bleeding was secondary to a steam pop-induced atrial tear. None of the postprocedural cases required FXaI reversal and the dose of rivaroxaban was temporarily reduced. No fatal outcomes or thromboembolic events were reported. Conclusion: Pericardiocentesis and drainage with FXaI reversal proved effective in the management of acute PEs with tamponade occurring periprocedurally in patients undergoing AF ablation with uninterrupted FXaI. Early postprocedural effusions can be treated with pericardiocentesis without the need of a reversal agent. C1 [Gianni, Carola; Di Biase, Luigi; Mohanty, Sanghamitra; Trivedi, Chintan; Bai, Rong; Al-Ahmad, Amin; Burkhardt, J. David; Gallinghouse, G. Joseph; Horton, Rodney P.; Sanchez, Javier E.; Hranitzky, Patrick M.; Natale, Andrea] St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, 3000 N IH-35,Suite 720, Austin, TX 78705 USA. [Gianni, Carola] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. [Di Biase, Luigi; Natale, Andrea] Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY 10467 USA. [Di Biase, Luigi; Horton, Rodney P.; Natale, Andrea] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Di Biase, Luigi] Univ Foggia, Dept Clin & Expt Med, Foggia, Italy. [Lakkireddy, Dhanunjaya] Univ Kansas, Med Ctr, Div Cardiovasc Dis, Kansas City, KS 66103 USA. [Mansour, Moussa C.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Div Electrophysiol, Boston, MA 02114 USA. [Santangeli, Pasquale; Zado, Erica S.; Marchlinski, Francis E.] Hosp Univ Penn, Div Cardiovasc, Electrophysiol Sect, 3400 Spruce St, Philadelphia, PA 19104 USA. [Beheiry, Salwa; Hao, Steven C.; Natale, Andrea] Calif Pacific Med Ctr, Electrophysiol & Arrhythmia Serv, San Francisco, CA USA. [Couts, Linda; Gibson, Douglas; Natale, Andrea] Scripps Clin, Intervent Electrophysiol, La Jolla, CA 92037 USA. [Natale, Andrea] Case Western Reserve Univ, Sch Med, Metrohlth Med Ctr, Cleveland, OH USA. [Natale, Andrea] Stanford Univ, Div Cardiol, Stanford, CA 94305 USA. [Natale, Andrea] Univ Texas Austin, Dell Med Sch, Austin, TX 78712 USA. RP Gianni, C (reprint author), St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, 3000 N IH-35,Suite 720, Austin, TX 78705 USA. EM carola.gianni@unimi.it OI Di Biase, Luigi/0000-0001-6508-4047 NR 24 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD APR PY 2016 VL 27 IS 4 BP 399 EP 403 DI 10.1111/jce.12918 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DJ6HP UT WOS:000374312200004 PM 26756289 ER PT J AU Piccart-Gebhart, M Holmes, E Baselga, J de Azambuja, E Dueck, AC Viale, G Zujewski, JA Goldhirsch, A Armour, A Pritchard, KI McCullough, AE Dolci, S McFadden, E Holmes, AP Liu, TH Eidtmann, H Dinh, P Di Cosimo, S Harbeck, N Tjulandin, S Im, YH Huang, CS Dieras, V Hillman, DW Wolff, AC Jackisch, C Lang, I Untch, M Smith, I Boyle, F Xu, BH Gomez, H Suter, T Gelber, RD Perez, EA AF Piccart-Gebhart, Martine Holmes, Eileen Baselga, Jose de Azambuja, Evandro Dueck, Amylou C. Viale, Giuseppe Zujewski, Jo Anne Goldhirsch, Aron Armour, Alison Pritchard, Kathleen I. McCullough, Ann E. Dolci, Stella McFadden, Eleanor Holmes, Andrew P. Liu Tonghua Eidtmann, Holger Phuong Dinh Di Cosimo, Serena Harbeck, Nadia Tjulandin, Sergei Im, Young-Hyuck Huang, Chiun-Sheng Dieras, Veronique Hillman, David W. Wolff, Antonio C. Jackisch, Christian Lang, Istvan Untch, Michael Smith, Ian Boyle, Frances Xu, Binghe Gomez, Henry Suter, Thomas Gelber, Richard D. Perez, Edith A. TI Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OPEN-LABEL; PLUS CAPECITABINE; CHEMOTHERAPY; THERAPY; SURVIVAL; EFFICACY; SAFETY; COMBINATION; INHIBITOR; DOCETAXEL AB Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2-positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2-positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T. L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P <= .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T. L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. C1 [de Azambuja, Evandro] Inst Jules Bordet, Blvd Waterloo 121, B-1000 Brussels, Belgium. [Piccart-Gebhart, Martine] Univ Libre Bruxelles, Brussels, Belgium. [Holmes, Eileen; McFadden, Eleanor; Holmes, Andrew P.] Frontier Sci Scotland, Kincraig, Kingussie, Scotland. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [de Azambuja, Evandro; Dolci, Stella] Breast European Adjuvant Study Team, Brussels, Belgium. [Dueck, Amylou C.; McCullough, Ann E.] Mayo Clin, Scottsdale, AZ USA. [Viale, Giuseppe] Univ Milan, Milan, Italy. [Viale, Giuseppe; Goldhirsch, Aron] Ist Europeo Oncol, Milan, Italy. [Zujewski, Jo Anne] NCI, Bethesda, MD 20892 USA. [Goldhirsch, Aron] Osped Reg Lugano, Viganello Lugano, Switzerland. [Armour, Alison] GlaxoSmithKline, Collegeville, PA USA. [Pritchard, Kathleen I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Pritchard, Kathleen I.] Univ Toronto, Toronto, ON, Canada. [Liu Tonghua] Beijing Union Med Coll Hosp, Beijing, Peoples R China. [Liu Tonghua; Xu, Binghe] China Acad Chinese Med Sci, Beijing, Peoples R China. [Eidtmann, Holger] Univ Hosp Kiel, Kiel, Germany. [Phuong Dinh] Breast Int Grp, Brussels, Belgium. [Di Cosimo, Serena] Ist Nazl Tumori, Via Venezian 1, I-20133 Milan, Italy. [Di Cosimo, Serena] SOLTI Breast Canc Res Grp, Barcelona, Spain. [Harbeck, Nadia] Frauenklin Univ Munchen, Munich, Germany. [Tjulandin, Sergei] RAMS, Blokhin Russian Canc Res Ctr, Moscow, Russia. [Im, Young-Hyuck] Korean Canc Study Grp, Seoul, South Korea. [Im, Young-Hyuck] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Huang, Chiun-Sheng] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Dieras, Veronique] Inst Curie, Paris, France. [Hillman, David W.] Mayo Clin, Rochester, MN USA. [Wolff, Antonio C.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Jackisch, Christian] Klinikum Offenbach, Offenbach, Germany. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Untch, Michael] Helios Klinikum Berlin Buch, Berlin, Germany. [Smith, Ian] Royal Marsden Hosp NHS Trust Surrey, Sutton, Surrey, England. [Boyle, Frances] Univ Sydney, Mater Hosp, Patricia Ritchie Ctr Canc Care & Res, Sydney, NSW, Australia. [Gomez, Henry] Inst Nacl Enfermedades Neoplas, Lima, Peru. [Suter, Thomas] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. RP Piccart-Gebhart, M (reprint author), Inst Jules Bordet, Blvd Waterloo 121, B-1000 Brussels, Belgium. EM martine.piccart@bordet.be RI Serena, Di Cosimo/E-9418-2017 OI Serena, Di Cosimo/0000-0002-4666-8052 FU GlaxoSmithKline; National Cancer Institute of the National Institutes of Health [U10CA180821, U10CA180882, CA025224] FX Supported by GlaxoSmithKline and the National Cancer Institute of the National Institutes of Health under Grant No. U10CA180821 and U10CA180882 to the Alliance for Clinical Trials in Oncology and CA025224 to the legacy North Central Cancer Treatment Group. NR 33 TC 29 Z9 29 U1 0 U2 10 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 APR 1 PY 2016 VL 34 IS 10 BP 1034 EP + DI 10.1200/JCO.2015.62.1797 PG 25 WC Oncology SC Oncology GA DJ6PA UT WOS:000374334200008 PM 26598744 ER PT J AU Grover, S Lim, RM Blumberg, RS Syngal, S AF Grover, Shilpa Lim, Ramona M. Blumberg, Richard S. Syngal, Sapna TI Oncogastroenterology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID GASTROINTESTINAL PROBLEMS; CANCER; RADIOTHERAPY; SYMPTOMS C1 [Grover, Shilpa; Lim, Ramona M.; Blumberg, Richard S.; Syngal, Sapna] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Grover, Shilpa; Lim, Ramona M.; Blumberg, Richard S.; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Lim, Ramona M.; Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Grover, S (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [P30 DK034854] NR 8 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 APR 1 PY 2016 VL 34 IS 10 BP 1154 EP + DI 10.1200/JCO.2015.65.7973 PG 3 WC Oncology SC Oncology GA DJ6PA UT WOS:000374334200026 PM 26834060 ER PT J AU Lee, EQ Ruland, S LeBoeuf, NR Wen, PY Santagata, S AF Lee, Eudocia Q. Ruland, Sandra LeBoeuf, Nicole R. Wen, Patrick Y. Santagata, Sandro TI Successful Treatment of a Progressive BRAF V600E-Mutated Anaplastic Pleomorphic Xanthoastrocytoma With Vemurafenib Monotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MELANOMA; GLIOMAS; CANCER C1 [Lee, Eudocia Q.; Ruland, Sandra; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Lee, Eudocia Q.; Wen, Patrick Y.; Santagata, Sandro] Harvard Univ, Sch Med, Boston, MA USA. [LeBoeuf, Nicole R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [LeBoeuf, Nicole R.; Santagata, Sandro] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Lee, EQ (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. NR 18 TC 10 Z9 10 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 APR 1 PY 2016 VL 34 IS 10 BP E87 EP E89 DI 10.1200/JCO.2013.51.1766 PG 3 WC Oncology SC Oncology GA DJ6PA UT WOS:000374334200002 PM 25092772 ER PT J AU Moy, AP Murali, M Nazarian, RM AF Moy, Andrea P. Murali, Mandakolathur Nazarian, Rosalynn M. TI Identification of a Th2-and Th17-skewed immune phenotype in chronic urticaria with Th22 reduction dependent on autoimmunity and thyroid disease markers SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE immunology; T lymphocytes; Th cell; urticaria ID CHRONIC IDIOPATHIC URTICARIA; FC-EPSILON-RI; THYMIC STROMAL LYMPHOPOIETIN; ANTI-IGE AUTOANTIBODIES; MAST-CELLS; ATOPIC-DERMATITIS; LESIONAL SKIN; T-CELLS; CYTOKINES; HISTAMINE AB Background Chronic urticaria is a condition with many inciting factors and often presents a therapeutic challenge to clinicians. In addition to a central role for mast cells, an immune dysregulated state related to cytokine/chemokine alterations is increasingly being recognized. Methods Biopsies of chronic urticaria (n = 11) and normal skin (n = 5) were evaluated with immunostains for CD117, CD3 and dual stains for CD4/T-bet, GATA-3, STAT-3 or BNC-2 (transcription factors specific and mutually exclusive for Th1, Th2, Th17 and Th22 cells, respectively). Clinical data, including autoantibodies and thyroid function tests, and the number of CD117+ mast cells and percent of Th1, Th2, Th17 and Th22 of CD3+ T-cells were compared. Results Th2 cells and Th17 cells were significantly more frequent in chronic urticaria than controls. In contrast, there was no significant difference in mast cells, Th1 cells or Th22 cells. Three of nine chronic urticaria patients had evidence of autoimmune disease; biopsies from these patients trended toward a greater number of mast cells and decreased percent of Th-cell subtypes as compared with those without autoimmunity markers, with significantly less Th22 cells. Conclusions These findings provide novel insight into the role of Th2 and Th17 in chronic urticaria pathophysiology and may impact therapy. C1 [Moy, Andrea P.; Murali, Mandakolathur; Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St,Warren 829A, Boston, MA 02114 USA. [Moy, Andrea P.; Murali, Mandakolathur; Nazarian, Rosalynn M.] Harvard Univ, Sch Med, Boston, MA USA. [Murali, Mandakolathur] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Nazarian, RM (reprint author), Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St,Warren 829A, Boston, MA 02114 USA. EM rmnazarian@partners.org NR 52 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2016 VL 43 IS 4 BP 372 EP 378 DI 10.1111/cup.12673 PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA DJ6RI UT WOS:000374340200010 PM 26785710 ER PT J AU Linnemann, AK Davis, DB AF Linnemann, Amelia K. Davis, Dawn Belt TI Glucagon-like peptide-1 and cholecystokinin production and signaling in the pancreatic islet as an adaptive response to obesity SO JOURNAL OF DIABETES INVESTIGATION LA English DT Article DE Cholecystokinin; Glucagon-like peptide-1; Pancreatic islet ID BETA-CELL MASS; FAT-FED MICE; TRANSCRIPTION FACTORS; GENE-TRANSCRIPTION; INSULIN-SECRETION; GLP-1 RECEPTORS; MOUSE MODELS; DOUBLE-BLIND; ALPHA-CELLS; IN-VITRO AB Precise control of blood glucose is dependent on adequate -cell mass and function. Thus, reductions in -cell mass and function lead to insufficient insulin production to meet demand, and result in diabetes. Recent evidence suggests that paracrine signaling in the islet might be important in obesity, and disruption of this signaling could play a role in the pathogenesis of diabetes. For example, we recently discovered a novel islet incretin axis where glucagon-like peptide-1 regulates -cell production of another classic gut hormone, cholecystokinin. This axis is stimulated by obesity, and plays a role in enhancing -cell survival. In the present review, we place our observations in the wider context of the literature on incretin regulation in the islet, and discuss the potential for therapeutic targeting of these pathways. C1 [Linnemann, Amelia K.; Davis, Dawn Belt] Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI USA. [Davis, Dawn Belt] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Linnemann, AK (reprint author), Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI USA. EM alinnemann@medicine.wisc.edu FU BLRD VA [I01 BX001880]; NIDDK NIH HHS [K01 DK102492] NR 50 TC 1 Z9 1 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2040-1116 EI 2040-1124 J9 J DIABETES INVEST JI J. Diabetes Investig. PD APR PY 2016 VL 7 SU 1 SI SI BP 44 EP 49 DI 10.1111/jdi.12465 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DK1HN UT WOS:000374663200009 PM 27186355 ER PT J AU Watanabe, C Komoto, S Tomita, K Hokari, R Tanaka, M Hirata, I Hibi, T Kaunitz, JD Miura, S AF Watanabe, Chikako Komoto, Shunsuke Tomita, Kengo Hokari, Ryota Tanaka, Masanori Hirata, Ichiro Hibi, Toshifumi Kaunitz, Jonathan D. Miura, Soichiro TI Endoscopic and clinical evaluation of treatment and prognosis of Cronkhite-Canada syndrome: a Japanese nationwide survey SO JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Acquired gastrointestinal polyposis syndrome; Malnutrition; Gastric cancer; Colon cancer ID INTRAMUCOSAL GASTRIC-CANCER; GASTROINTESTINAL POLYPOSIS; COLON-CANCER; REMISSION; MANAGEMENT; DIAGNOSIS; PATHOLOGY; ALOPECIA AB Background First reported in 1955, Cronkhite-Canada syndrome (CCS), a rare syndrome characterized by ectodermal abnormalities and inflammatory changes of the gastrointestinal tract mucosa, has been associated with a poor prognosis and life-threatening malignant complications. In a large population survey, we endeavored to characterize the course and treatment outcome of CCS through clinical and endoscopic assessment, and to explore its optimal treatment and surveillance strategy. Methods A retrospective analysis of 210 patients with CCS was conducted via a questionnaire-based nationwide survey of 983 teaching hospitals located throughout Japan. We assessed clinical features, endoscopic findings, treatments used, and short-and long-term outcomes. Results The average age at diagnosis was 63.5 years. In all cases, upper or lower gastrointestinal tract polyposis was confirmed, accompanied by characteristic ectodermal abnormalities. Of the treatments used, oral corticosteroids (30-49 mg/day) were the most effective treatment for active disease, with adjunctive nutritional support considered beneficial. With corticosteroid treatment, abdominal symptoms were relieved within a few months, whereas polyp regression often required more than 6 months. Maintenance of endoscopic remission with or without steroids for 3 years significantly lowered the development of CCS-related cancer, compared with relapsers or nonresponders, underscoring the importance of sustained endoscopic remission for cancer prevention. Conclusions The prognosis of CCS has greatly improved through the use of improved medical treatment. Although CCS continues to be relentlessly progressive, carrying a high cancer risk, a sufficient dose and duration of corticosteroid therapy accompanied by nutritional support and periodic endoscopic surveillance appears to improve its natural history. C1 [Watanabe, Chikako; Komoto, Shunsuke; Tomita, Kengo; Hokari, Ryota; Miura, Soichiro] Natl Def Med Coll, Dept Internal Med, 3-2 Namiki, Tokorozawa, Saitama 3598513, Japan. [Tanaka, Masanori] Hirosaki City Hosp, Dept Pathol & Lab Med, Aomori, Japan. [Hirata, Ichiro] Fujita Hlth Univ, Dept Gastroenterol, Toyoake, Aichi, Japan. [Hibi, Toshifumi] Kitasato Inst Hosp, Ctr Adv IBD Res & Treatment, Tokyo, Japan. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles VA Med Ctr, Los Angeles, CA 90095 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. RP Watanabe, C (reprint author), Natl Def Med Coll, Dept Internal Med, 3-2 Namiki, Tokorozawa, Saitama 3598513, Japan. EM chikakow@ndmc.ac.jp FU Ministry of Health, Labour and Welfare of Japan; Japanese Ministry of Education, Culture, Sports, Science and Technology FX This study was supported by a Grant-in-Aid for the Intractable Disease Project of the Ministry of Health, Labour and Welfare of Japan, and by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The authors thank the following institutions for replying to the questionnaires in the first and second surveys: Asahikawa Medical University, Sapporo Medical University Hospital, Hokkaido University Hospital, Kushiro Rosai Hospital, KKR Sapporo Medical Center, National Hospital Organization Hokkaido Medical Center, Sapporo Higashi Tokushukai Hospital, Sunagawa City Medical Center, Iwate Medical University, Tohoku University Hospital, Akita University Hospital, Nakadori General Hospital, Tokyo Medical University Ibaraki Medical Center, Jichi Medical University Hospital, Isesaki Municipal Hospital, Saitama Medical University Hospital, Dokkyo Medical University Koshigaya Hospital, Saiseikai Kawaguchi General Hospital, Saitama Medical Center Jichi Medical University, Sekishindo Hospital, Chiba University Hospital, Funabashi Municipal Medical Center, The University of Tokyo Hospital, Kyorin University Hospital, Keio University Hospital, Tokyo Medical University Hachioji Medical Center, Tokyo Women's Medical University Hospital, Nihon University Itabashi Hospital, NTT Medical Center Tokyo, The Cancer Institute Hospital of JFCR, Hiratsuka GI Hospital, Kitasato University Kitasato Institute Hospital, Sanno Hospital, Shiseikai Daini Hospital, Toho University Ohashi Medical Center, Mishuku Hospital, Kitasato University Hospital, Showa University Fujigaoka Hospital, St. Marianna University School of Medicine, Yokohama City Seibu Hospital, Yokosuka Kyosai Hospital, Saiseikai Yokohamashi Nanbu Hospital, Nihon Koukan Hospital, Yokohama Sakae Kyosai Hospital, Federation of National Public Service Personnel Mutual Associations, National Hospital Organization Shinshu Ueda Medical Center, Niigata City General Hospital, Kanazawa University Hospital, Public Central Hospital of Matto Ishikawa, Toyama Rosai Hospital, Gifu Municipal Hospital, Nagano Chuo Hospital, Toki General Hospital, Juntendo Hospital Shizuoka Hospital, Hamamatsu Medical Center, Hamamatsu South Hospital, Nagoya City University Hospital, Fujita Health University Hospital, Aichi Cancer Center Hospital, Japanese Red Cross Nagoya Daiichi Hospital, Kainan Hospital, Daiyukai General Hospital, Saiseikai Matsusaka General Hospital, Japanese Red Cross Society Nagahama Hospital, Mitsubishi Kyoto Hospital, Osaka City University Hospital, Osaka Medical College Hospital, Kinki University Hospital, Osaka General Medical Center, Osaka Red Cross Hospital, Kitano Hospital, Osaka Saiseikai Nakatsu Hospital, Ishikiriseikikai Hospital, Sakai City Hospital, Yodogawa Christian Hospital, Maki Hospital, Kobe University Hospital, Hyogo College of Medicine, Takarazuka City Hospital, St.; Mary's Hospital, Miki-Sanyo Hospital, Yamato Takada Municipal Hospital, Wakayama Medical University Hospital, Shimane University Hospital, Masuda Red Cross Hospital, Okayama University Hospital, Kawasaki Medical School Hospital, Hiroshima City Hiroshima Citizens Hospital, Hiroshima General Hospital of West Japan Railway Company, Hiroshima City Asa Hospital, Yamaguchi University Hospital, Tokuyama Central Hospital, Yamaguchi Red Cross Hospital, Tokushima Prefecture Naruto Hospital, Tokushima Red Cross Hospital, Uwajima City Hospital, Matsuyama Red Cross Hospital, National Hospital Organization Kochi National Hospital, Takamatsu Municipal Hospital, Kurume University Hospital, Kitakyushu Municipal Medical Center, Tagawa Hospital, Kyushu Central Hospital, Fukuoka Higashi Medical Center, Nagata Hospital, Wakamatsu Hospital, University of Occupational and Environmental Health, Japan, Saga University Hospital, Kumamoto University Hospital, Beppu Medical Center, Nakatsu Municipal Hospital, Nakagami Hospital, Kyushu University Graduate School of Medical Sciences, Yame General Hospital, Fukuoka Sanno Hospital, University of Miyazaki Hospital, Iizuka Hospital, Kyoto University, Sapporo-Kosei General Hospital, Sannno Hospital, Nanbu Medical Center/Nanbu Child Medical Center, Jikei University, Jikei University Kashiwa Hospital, Jikei University Katsushika Medical Center, Nagoya Handa City Hospital, Tsuchiura Kyodo General Hospital, Yokohama Municipal Citizen's Hospital, Sano General Hospital, and National Defense Medical College. NR 47 TC 4 Z9 6 U1 2 U2 4 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0944-1174 EI 1435-5922 J9 J GASTROENTEROL JI J. Gastroenterol. PD APR PY 2016 VL 51 IS 4 BP 327 EP 336 DI 10.1007/s00535-015-1107-7 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DK1JT UT WOS:000374669000003 PM 26216651 ER PT J AU Linda, W Mei, Y Agarwalla, PK Beroukhim, R Dunn, IF AF Linda, Wenya Mei, Yu Agarwalla, Pankaj K. Beroukhim, Rameen Dunn, Ian F. TI Genomic and Epigenomic Landscape in Meningioma SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Meningioma; Genomics; Epigenetics; Molecular taxonomy; Precision medicine ID ATYPICAL CRANIAL MENINGIOMAS; HUMAN-MALIGNANT MENINGIOMAS; ANAPLASTIC MENINGIOMAS; TELOMERASE ACTIVITY; DNA METHYLATION; HISTONE METHYLTRANSFERASE; INTRACRANIAL MENINGIOMAS; ADJUVANT RADIATION; ALLELIC LOSSES; STEM-CELLS AB Meningiomas are the most common primary intracranial neoplasms in adults. Despite their prevalence, their biologic underpinnings remain incompletely described. The recent application of unbiased next-generation sequencing and epigenomic approaches has implicated a new array of candidate biomarkers and oncogenic drivers. These insights may serve to craft a molecular taxonomy for meningiomas and highlight putative therapeutic targets in an era of biology-informed precision medicine. C1 [Linda, Wenya; Mei, Yu; Dunn, Ian F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, 15 Francis St,PBB 3, Boston, MA 02115 USA. [Linda, Wenya; Agarwalla, Pankaj K.; Beroukhim, Rameen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. RP Dunn, IF (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 15 Francis St, Boston, MA 02115 USA. EM idunn@partners.org NR 94 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3680 EI 1558-1349 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD APR PY 2016 VL 27 IS 2 BP 167 EP + DI 10.1016/j.nec.2015.11.009 PG 14 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DK0SA UT WOS:000374621300005 ER PT J AU Sparks, TN Griffin, E Page, J Pilliod, R Shaffer, BL Caughey, AB AF Sparks, Teresa N. Griffin, Emily Page, Jessica Pilliod, Rachel Shaffer, Brian L. Caughey, Aaron B. TI Down syndrome: perinatal mortality risks with each additional week of expectant management SO PRENATAL DIAGNOSIS LA English DT Article ID SYNDROME FETUSES; GESTATIONAL-AGE; MATERNAL AGE; SYNDROME PREGNANCIES; UNITED-STATES; FETAL LOSS; STILLBIRTH; INFANTS; DEATH; TERM AB ObjectiveTo evaluate the gestational age (GA) at which perinatal mortality risk is minimized for fetuses with Down syndrome (DS). MethodsRetrospective cohort of singleton pregnancies delivered between 24 and 41weeks, using 2005-2006 United States linked birth and death certificate data. Among fetal DS cases, prospective risk of intrauterine fetal demise (IUFD) and risk of infant death were calculated for each week, and composite risk of fetal/infant mortality with expectant management was compared to delivery. ResultsOf 3113098 pregnancies, 1766 had fetal DS (0.06%). IUFD occurred in 7.4% with DS, and infant death in 6.5%. Prospective risk of IUFD increased from 37weeks onward to reach 50.7 per 1000 pregnancies (95% CI 33.2-68.3) at 42weeks. Comparing mortality with expectant management to delivery, expectant management carried increasing risk from 38 (RR 1.18; 95% CI 1.05-1.33) to 41weeks (RR 1.84; 95% CI 1.66-2.05). Further, number needed to deliver to avoid one excess death decreased from 38 (109.17; 95% CI 64.52-344.83) to 41weeks (24.08; 95% CI 20.59-29.04). ConclusionsAlthough further research is needed to clarify risk factors for fetal and neonatal death in cases of DS, risk of perinatal mortality appears to be minimized with delivery at 38weeks. (c) 2016 John Wiley & Sons, Ltd. C1 [Sparks, Teresa N.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Sparks, Teresa N.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Griffin, Emily; Shaffer, Brian L.; Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Page, Jessica] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Pilliod, Rachel] Brigham & Womens Hosp, Dept Obstet, 75 Francis St, Boston, MA 02115 USA. [Pilliod, Rachel] Brigham & Womens Hosp, Dept Gynecol, 75 Francis St, Boston, MA 02115 USA. [Pilliod, Rachel] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sparks, TN (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.; Sparks, TN (reprint author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. EM teresa.sparks@ucsf.edu OI Sparks, Teresa/0000-0002-8593-2186 NR 30 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0197-3851 EI 1097-0223 J9 PRENATAL DIAG JI Prenat. Diagn. PD APR PY 2016 VL 36 IS 4 BP 368 EP 374 DI 10.1002/pd.4792 PG 7 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA DK1OL UT WOS:000374682300011 PM 26891366 ER PT J AU Lee, JY Chitnis, T AF Lee, Ji Y. Chitnis, Tanuja TI Pediatric Multiple Sclerosis SO SEMINARS IN NEUROLOGY LA English DT Article DE multiple sclerosis; children; demyelination; diagnosis; treatment ID TRANSVERSE MYELITIS; CLINICAL-FEATURES; RELAPSE RATE; FOLLOW-UP; CHILDREN; ONSET; MS; ADOLESCENTS; CHILDHOOD; INTERFERON-BETA-1A AB Pediatric multiple sclerosis (MS) is a chronic inflammatory neurologic disease that is challenging to diagnose and treat. Although there are many clinical parallels between pediatric-onset MS and adult-onset MS, there is also accumulating evidence of distinguishing clinical features that may, in part, arise from development-specific, neuroimmune processes governing MS pathogenesis in children. Here the authors describe the clinical features, diagnosis, and treatment of pediatric MS, with a particular focus on describing clinical features and highlighting new developments that promise a better understanding of pediatric MS pathogenesis. An important task that lies ahead for pediatric neurologists is better understanding the early gene environment interaction that precipitates the first demyelinating event in pediatric MS. This area is of particular importance for understanding the MS etiology and the natural history of pediatric MS. Such understanding should in turn inform new developments in diagnostic tools, long-term therapies, and much-needed biomarkers. Such biomarkers are not only valuable for defining the disease onset, but also for monitoring both the treatment response and a disease evolution that spans multiple decades in children with MS. C1 [Lee, Ji Y.; Chitnis, Tanuja] Harvard Univ, Sch Med, Dept Pediat Neurol, Massachusetts Gen Hosp, 55 Fruit St,ACC708, Boston, MA 02114 USA. RP Chitnis, T (reprint author), Harvard Univ, Sch Med, Dept Pediat Neurol, Massachusetts Gen Hosp, 55 Fruit St,ACC708, Boston, MA 02114 USA. EM tchitnis@partners.org NR 35 TC 1 Z9 1 U1 3 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 EI 1098-9021 J9 SEMIN NEUROL JI Semin. Neurol. PD APR PY 2016 VL 36 IS 2 BP 148 EP 153 DI 10.1055/s-0036-1579738 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA DK0QN UT WOS:000374617400007 PM 27116721 ER PT J AU Wintner, A Kim, MM Bechis, SK Kreydin, EI AF Wintner, Anton Kim, Michelle M. Bechis, Seth K. Kreydin, Evgeniy I. TI Voiding Dysfunction in Multiple Sclerosis (vol 36, pg 212, 2016) SO SEMINARS IN NEUROLOGY LA English DT Correction C1 [Wintner, Anton; Kim, Michelle M.; Bechis, Seth K.] Harvard Univ, Dept Urol, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Kreydin, Evgeniy I.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, 300 Stein Plaza,3rd Floor, Los Angeles, CA 90095 USA. RP Kreydin, EI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, 300 Stein Plaza,3rd Floor, Los Angeles, CA 90095 USA. EM ekreydin@mednet.ucla.edu NR 1 TC 2 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 EI 1098-9021 J9 SEMIN NEUROL JI Semin. Neurol. PD APR PY 2016 VL 36 IS 2 BP 219 EP 219 DI 10.1055/s-0036-1582255 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA DK0QN UT WOS:000374617400015 PM 27116728 ER PT J AU Greer, JB Ferrone, CR AF Greer, Jonathan B. Ferrone, Cristina R. TI Spectrum and Classification of Cystic Neoplasms of the Pancreas SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Cystic neoplasms of the pancreas; Mucinous cystic neoplasm; Serous cystic neoplasm; Cystic pancreatic endocrine neoplasm; Solid pseudopapillary neoplasm; Intraductal papillary mucinous neoplasm ID PAPILLARY MUCINOUS NEOPLASMS; SOLID-PSEUDOPAPILLARY TUMORS; ENDOCRINE NEOPLASMS; SEROUS-CYSTADENOMA; HIGH-RISK; MANAGEMENT; PROGNOSIS; DUCT; IPMN; RECOMMENDATIONS AB As patients are living longer and axial imaging is more widespread, increasing numbers of cystic neoplasms of the pancreas are found. Intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are the most common. The revised Sendai guidelines provide a safe algorithm for expectant management of certain cystic neoplasms; however, studies are ongoing to identify further subgroups that can be treated nonoperatively. For those patients with high-risk clinical features or symptoms, surgical resection can be performed safely at high-volume pancreatic centers. Accurate diagnosis is critical for accurate decision making. C1 [Greer, Jonathan B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gen Surg,Dept Surg, 55 Fruit St,GRB-425, Boston, MA 02114 USA. [Ferrone, Cristina R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM cferrone@mgh.harvard.edu NR 49 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 EI 1558-5042 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD APR PY 2016 VL 25 IS 2 BP 339 EP + DI 10.1016/j.soc.2015.11.002 PG 13 WC Oncology; Surgery SC Oncology; Surgery GA DK0SF UT WOS:000374621800010 PM 27013368 ER PT J AU Chan, JA Kulke, MH AF Chan, Jennifer A. Kulke, Matthew H. TI Medical Management of Pancreatic Neuroendocrine Tumors: Current and Future Therapy SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Pancreatic neuroendocrine tumor; Somatostatin analogue; mTOR; Everolimus; Sunitinib; Temozolomide ID RADIOLABELED SOMATOSTATIN ANALOG; ENDOTHELIAL GROWTH-FACTOR; ISLET-CELL-CARCINOMA; ENDOCRINE CARCINOMAS; PHASE-II; PROGNOSTIC-FACTORS; GRADING SYSTEM; MTOR PATHWAY; EXPRESSION; TEMOZOLOMIDE AB When diagnosed at an early stage, resection of pancreatic neuroendocrine tumors (NETs) is often curative. Unfortunately, curative surgery is rarely an option for patients with metastatic disease. Multiple options are available for the management of patients with advanced pancreatic NETs, including surgery, liver-directed therapy, and systemic therapies. Because of the heterogeneity of disease biology and presentation, a multidisciplinary approach to management is critical. Treatment with somatostatin analogs, sunitinib, everolimus, and alkylating agents provide effective systemic therapeutic options for patients. Future studies to evaluate the optimal timing, sequence, and combination of therapies, as well as to identify predictors of response, are warranted. C1 [Chan, Jennifer A.; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Dana 1220,450 Brookline Ave, Boston, MA 02215 USA. RP Chan, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 1220,450 Brookline Ave, Boston, MA 02215 USA. EM jang@partners.org FU Novartis; Sanofi-Aventis FX Dr J.A. Chan has received institutional research funding from Novartis and Sanofi-Aventis. She has served as an advisor for Ipsen and Novartis and holds stock in Merck. Dr M.H. Kulke has served as an advisor for Ipsen and Novartis. NR 68 TC 1 Z9 1 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 EI 1558-5042 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD APR PY 2016 VL 25 IS 2 BP 423 EP + DI 10.1016/j.soc.2015.11.009 PG 16 WC Oncology; Surgery SC Oncology; Surgery GA DK0SF UT WOS:000374621800015 PM 27013373 ER PT J AU Poon, SJ Greenwood-Ericksen, MB Gish, RE Neri, PM Takhar, SS Weiner, SG Schuur, JD Landman, AB AF Poon, Sabrina J. Greenwood-Ericksen, Margaret B. Gish, Rebecca E. Neri, Pamela M. Takhar, Sukhjit S. Weiner, Scott G. Schuur, Jeremiah D. Landman, Adam B. TI Usability of the Massachusetts Prescription Drug Monitoring Program in the Emergency Department: A Mixed-methods Study SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID OVERDOSE; IMPACT AB ObjectivesPrescription drug monitoring programs (PDMPs) are underutilized, despite evidence showing that they may reduce the epidemic of opioid-related addiction, diversion, and overdose. We evaluated the usability of the Massachusetts (MA) PDMP by emergency medicine providers (EPs), as a system's usability may affect how often it is used. MethodsThis was a mixed-methods study of 17 EPs. We compared the time and number of clicks required to review one patient's record in the PDMP to three other commonly performed computer-based tasks in the emergency department (ED: ordering a computed tomography [CT] scan, writing a prescription, and searching a medication history service integrated within the electronic medical record [EMR]). We performed semistructured interviews and analyzed participant comments and responses regarding their experience using the MA PDMP. ResultsThe PDMP task took a longer time to complete (mean = 4.22 minutes) and greater number of mouse clicks to complete (mean = 50.3 clicks) than the three other tasks (CT-pulmonary embolism = 1.42 minutes, 24.8 clicks; prescription = 1.30 minutes, 19.5 clicks; SureScripts = 1.45 minutes, 9.5 clicks). Qualitative analysis yielded four main themes about PDMP usability, three negative and one positive: 1) difficulty accessing the PDMP, 2) cumbersome acquiring patient medication history information within the PDMP, 3) nonintuitive display of patient medication history information within the PDMP, and 4) overall perceived value of the PDMP despite an inefficient interface. ConclusionsThe complicated processes of gaining access to, logging in, and using the MA PDMP are barriers to preventing its more frequent use. All states should evaluate the PDMP usability in multiple practice settings including the ED and work to improve provider enrollment, login procedures, patient information input, prescription data display, and ultimately, PDMP data integration into EMRs. C1 [Poon, Sabrina J.; Greenwood-Ericksen, Margaret B.] Harvard Affiliated Emergency Med Residency, Boston, MA USA. [Poon, Sabrina J.; Greenwood-Ericksen, Margaret B.; Gish, Rebecca E.; Takhar, Sukhjit S.; Weiner, Scott G.; Schuur, Jeremiah D.; Landman, Adam B.] Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. [Poon, Sabrina J.; Greenwood-Ericksen, Margaret B.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Takhar, Sukhjit S.; Weiner, Scott G.; Schuur, Jeremiah D.; Landman, Adam B.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Neri, Pamela M.] Partners Healthcare, Clin & Qual Anal, Wellesley, MA USA. RP Poon, SJ (reprint author), Harvard Affiliated Emergency Med Residency, Boston, MA USA.; Poon, SJ (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA.; Poon, SJ (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM sjpoon@partners.org FU Emergency Medicine Foundation/Emergency Medicine Residents' Association (EMF/EMRA) Resident Research Grant FX This project was supported by the Emergency Medicine Foundation/Emergency Medicine Residents' Association (EMF/EMRA) Resident Research Grant. NR 20 TC 0 Z9 0 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2016 VL 23 IS 4 BP 406 EP 414 DI 10.1111/acem.12905 PG 9 WC Emergency Medicine SC Emergency Medicine GA DJ2OU UT WOS:000374045200005 PM 26806310 ER PT J AU Milling, TJ Refaai, MA Sarode, R Lewis, B Mangione, A Durn, BL Harman, A Lee, ML Goldstein, JN AF Milling, Truman J., Jr. Refaai, Majed A. Sarode, Ravi Lewis, Brandon Mangione, Antoinette Durn, Billie L. Harman, Amy Lee, Martin L. Goldstein, Joshua N. TI Safety of a Four-factor Prothrombin Complex Concentrate Versus Plasma for Vitamin K Antagonist Reversal: An Integrated Analysis of Two Phase IIIb Clinical Trials SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID ORAL ANTICOAGULATION; RAPID REVERSAL; FROZEN PLASMA; MANAGEMENT; WARFARIN; EFFICACY; TRANSFUSION; GUIDELINES; BERIPLEX; RISK AB ObjectivesClinicians often need to rapidly reverse vitamin K antagonists (VKAs) in the setting of major hemorrhage or urgent need for surgery. Little is known about the safety profile of the traditional reversal agent, plasma, or the newly approved agent, four-factor prothrombin complex concentrate (4F-PCC), in a randomized setting. This is an integrated analysis of safety data from two clinical trials that evaluated 4F-PCC versus plasma for the treatment of patients requiring rapid VKA reversal for acute major bleeding or prior to an urgent surgical/invasive procedure. MethodsThis descriptive analysis comprised adverse event (AE) data from two phase IIIb, randomized, controlled trials. The bleeding and surgical studies were performed across 36 and 33 sites, respectively, in nine countries, with the integrated analysis comprising 388 patients (4F-PCC, n = 191; plasma, n = 197) aged 18 years, who required VKA reversal due to major bleeding or prior to an urgent surgical/invasive procedure. Patients received either 4F-PCC, containing nonactivated factors II, VII, IX, and X and proteins C and S (Beriplex/Kcentra, CSL Behring) or plasma, both dosed according to baseline international normalized ratio and body weight. Patients were also to receive vitamin K1. AEs and serious AEs (SAEs) were assessed up to days 10 and 45, respectively. ResultsThe proportion of patients with AEs (4F-PCC, 115/191 [60.2%]; plasma, 124/197 [62.9%]) and SAEs (4F-PCC, 54/191 [28.3%]; plasma, 49/197 [24.9%]) was similar between groups. The proportion of patients with thromboembolic events was also similar between groups (4F-PCC, 14/191 [7.3%]; plasma, 14/197 [7.1%]). There were 13 (6.8%) deaths in the 4F-PCC group and 13 (6.6%) in the plasma group. Fluid overload events occurred in more patients in the plasma group than the 4F-PCC group (25 [12.7%] and 9 [4.7%], respectively). ConclusionsThese safety data represent the largest controlled assessment of a 4F-PCC to date. For patients requiring urgent VKA reversal, 4F-PCC had a safety profile similar to that of plasma (AEs, SAEs, thromboembolic events, and deaths), but was associated with fewer fluid overload events. C1 [Milling, Truman J., Jr.] Dell Univ Texas Med Sch, Univ Med Ctr Brackenridge, Dell Childrens Med Ctr, Seton Clin Res Inst, Austin, TX USA. [Refaai, Majed A.] Univ Rochester Med, Rochester, NY USA. [Sarode, Ravi] UT Southwestern Med Ctr, Dallas, TX USA. [Lewis, Brandon] Texas A& M Hlth Sci Ctr, St Joseph Reg Hlth Ctr, College Stn, TX USA. [Mangione, Antoinette; Durn, Billie L.; Harman, Amy] CSL Behring, King Of Prussia, PA USA. [Lee, Martin L.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Milling, TJ (reprint author), Dell Univ Texas Med Sch, Univ Med Ctr Brackenridge, Dell Childrens Med Ctr, Seton Clin Res Inst, Austin, TX USA. EM tjmilling@yahoo.com RI Goldstein, Joshua/H-8953-2016 FU CSL Behring FX TJM received consulting fees from CSL Behring and has been a member of a CSL Behring speakers bureau; MAR received consultancy fees from CSL Behring and is a member of a CSL Behring speakers bureau; RS received consulting fees and honoraria from CSL Behring and has served as a member of advisory boards for Octapharma, Instrument Laboratories, Alexion, and Kedrion; AM, BLD, and AH are employees of CSL Behring; MLL received consulting fees from CSL Behring; JNG received consulting fees and a research grant from CSL Behring; and BL declares no competing interests. NR 29 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2016 VL 23 IS 4 BP 466 EP 475 DI 10.1111/acem.12911 PG 10 WC Emergency Medicine SC Emergency Medicine GA DJ2OU UT WOS:000374045200012 PM 26822172 ER PT J AU Ingelfinger, JR Kalantar-Zadeh, K Schaefer, F AF Ingelfinger, Julie R. Kalantar-Zadeh, Kamyar Schaefer, Franz CA World Kidney Day Steering Comm TI Averting the Legacy of Kidney Disease-Focus on Childhood SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Editorial Material ID NEPHROLOGY ASSOCIATION IPNA; RENAL REPLACEMENT THERAPY; LOW-BIRTH-WEIGHT; INTERNATIONAL SOCIETY; CONSENSUS STATEMENT; PROSPECTIVE COHORT; BLOOD-PRESSURE; CHILDREN; EPIDEMIOLOGY; FAILURE C1 [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Boston, MA USA. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, MassGen Hosp Children, Dept Pediat Nephrol, Boston, MA 02114 USA. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, Dept Med, Div Nephrol & Hypertens, Irvine, CA 92717 USA. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, Dept Pediat & Publ Hlth, Irvine, CA 92717 USA. [Kalantar-Zadeh, Kamyar] Vet Affairs VA Long Beach Healthcare Syst, Long Beach, CA USA. [Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Schaefer, Franz] Heidelberg Univ, Dept Pediat, Heidelberg, Germany. [Schaefer, Franz] Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany. RP Ingelfinger, JR (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Dept Pediat Nephrol, Boston, MA 02114 USA. EM ingelfinger.julie@mgh.harvard.edu OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 33 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 2016 VL 29 IS 4 BP 537 EP 541 DI 10.1093/ajh/hpv193 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DJ5FJ UT WOS:000374231900017 PM 26965180 ER PT J AU Smith, SG Sestak, I Forster, A Partridge, A Side, L Wolf, MS Horne, R Wardle, J Cuzick, J AF Smith, S. G. Sestak, I. Forster, A. Partridge, A. Side, L. Wolf, M. S. Horne, R. Wardle, J. Cuzick, J. TI Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis SO ANNALS OF ONCOLOGY LA English DT Review DE preventive therapy; chemoprevention; decision-making; adherence; uptake; medication ID RANDOMIZED CONTROLLED-TRIAL; SURGICAL ADJUVANT BREAST; BRCA2 MUTATION CARRIERS; STAR P-2 TRIAL; ESTROGEN-RECEPTOR MODULATORS; BOWEL PROJECT P-1; QUALITY-OF-LIFE; HIGH-RISK; PREVENTION TRIAL; DECISION-MAKING AB In this systematic review of studies investigating decision-making in the context of breast cancer preventive therapy, we observed low uptake of all agents and poor long-term persistence. Our meta-analysis including over 21 000 women demonstrated that only 1 in 6 eligible women decided to take preventive therapy. Persistence for 5 years was low, limiting the preventive effect in these women.Preventive therapy is a risk reduction option for women who have an increased risk of breast cancer. The effectiveness of preventive therapy to reduce breast cancer incidence depends on adequate levels of uptake and adherence to therapy. We aimed to systematically review articles reporting uptake and adherence to therapeutic agents to prevent breast cancer among women at increased risk, and identify the psychological, clinical and demographic factors affecting these outcomes. Searches were carried out in PubMed, CINAHL, EMBASE and PsychInfo, yielding 3851 unique articles. Title, abstract and full text screening left 53 articles, and a further 4 studies were identified from reference lists, giving a total of 57. This review was prospectively registered with PROSPERO (CRD42014014957). Twenty-four articles reporting 26 studies of uptake in 21 423 women were included in a meta-analysis. The pooled uptake estimate was 16.3% [95% confidence interval (CI) 13.6-19.0], with high heterogeneity (I-2 = 98.9%, P < 0.001). Uptake was unaffected by study location or agent, but was significantly higher in trials [25.2% (95% CI 18.3-32.2)] than in non-trial settings [8.7% (95% CI 6.8-10.9)] (P < 0.001). Factors associated with higher uptake included having an abnormal biopsy, a physician recommendation, higher objective risk, fewer side-effect or trial concerns, and older age. Adherence (day-to-day use or persistence) over the first year was adequate. However, only one study reported a persistence of a parts per thousand yen80% by 5 years. Factors associated with lower adherence included allocation to tamoxifen (versus placebo or raloxifene), depression, smoking and older age. Risk of breast cancer was discussed in all qualitative studies. Uptake of therapeutic agents for the prevention of breast cancer is low, and long-term persistence is often insufficient for women to experience the full preventive effect. Uptake is higher in trials, suggesting further work should focus on implementing preventive therapy within routine care. C1 [Smith, S. G.; Sestak, I.; Cuzick, J.] Queen Mary Univ London, Wolfson Inst Prevent Med, London EC1M 6BQ, England. [Smith, S. G.; Forster, A.; Wardle, J.] UCL, Hlth Behav Res Ctr, London, England. [Partridge, A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Side, L.] UCL, Inst Womens Hlth, London, England. [Wolf, M. S.] Northwestern Univ, Div Gen Internal Med, Chicago, IL 60611 USA. [Horne, R.] UCL, Ctr Behav Med, London, England. RP Smith, SG (reprint author), Queen Mary Univ London, Ctr Canc Prevent, Wolfson Inst Prevent Med, Charterhouse Sq, London EC1M 6BQ, England. EM sam.smith@qmul.ac.uk FU Cancer Research UK [C42785/A17965]; Cancer Research UK-BUPA Cancer Prevention Postdoctoral Fellowship [C49896/A17429]; NIHR Collaboration for Leadership in Applied Research and Care (CLAHRC) North Thames FX SGS is supported by a Cancer Research UK Postdoctoral Fellowship (C42785/A17965). AF is supported by a Cancer Research UK-BUPA Cancer Prevention Postdoctoral Fellowship (C49896/A17429). RH is supported by NIHR Collaboration for Leadership in Applied Research and Care (CLAHRC) North Thames. The sponsor of the study played no role in the design, collection, analysis, interpretation of the data, writing of the manuscript or decision to submit the manuscript for publication. NR 94 TC 13 Z9 13 U1 4 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2016 VL 27 IS 4 BP 575 EP 590 DI 10.1093/annonc/mdv590 PG 16 WC Oncology SC Oncology GA DJ5HO UT WOS:000374237700005 PM 26646754 ER PT J AU Cavallari, M Dai, WY Guttmann, CRG Meier, DS Ngo, LH Hshieh, TT Callahan, AE Fong, TG Schmitt, E Dickerson, BC Press, DZ Marcantonio, ER Jones, RN Inouye, SK Alsop, DC AF Cavallari, Michele Dai, Weiying Guttmann, Charles R. G. Meier, Dominik S. Ngo, Long H. Hshieh, Tammy T. Callahan, Amy E. Fong, Tamara G. Schmitt, Eva Dickerson, Bradford C. Press, Daniel Z. Marcantonio, Edward R. Jones, Richard N. Inouye, Sharon K. Alsop, David C. CA SAGES Study Grp TI Neural substrates of vulnerability to postsurgical delirium as revealed by presurgical diffusion MRI SO BRAIN LA English DT Article DE delirium; temporal lobe; structural MRI; cognitive ageing; neuropsychiatry ID CONFUSION ASSESSMENT METHOD; WHITE-MATTER HYPERINTENSITIES; COGNITIVE-AFFECTIVE SYNDROME; CARE-UNIT SURVIVORS; POSTOPERATIVE DELIRIUM; ALZHEIMERS-DISEASE; MEAN DIFFUSIVITY; CARDIAC-SURGERY; HIP-FRACTURE; HUMAN BRAIN AB Despite the significant impact of postoperative delirium on surgical outcomes and the long-term prognosis of older patients, its neural basis has not yet been clarified. In this study we investigated the impact of premorbid brain microstructural integrity, as measured by diffusion tensor imaging before surgery, on postoperative delirium incidence and severity, as well as the relationship among presurgical cognitive performance, diffusion tensor imaging abnormalities and postoperative delirium. Presurgical diffusion tensor imaging scans of 136 older (a parts per thousand yen70 years), dementia-free subjects from the prospective Successful Aging after Elective Surgery study were analysed blind to the clinical data and delirium status. Primary outcomes were postoperative delirium incidence and severity during the hospital stay, as assessed by the Confusion Assessment Method. We measured cognition before surgery using general cognitive performance, a composite score based on a battery of neuropsychological tests. We investigated the association between presurgical diffusion tensor imaging parameters of brain microstructural integrity (i.e. fractional anisotropy, axial, mean and radial diffusivity) with postoperative delirium incidence and severity. Analyses were adjusted for the following potential confounders: age, gender, vascular comorbidity status, and general cognitive performance. Postoperative delirium occurred in 29 of 136 subjects (21%) during hospitalization. Presurgical diffusion tensor imaging abnormalities of the cerebellum, cingulum, corpus callosum, internal capsule, thalamus, basal forebrain, occipital, parietal and temporal lobes, including the hippocampus, were associated with delirium incidence and severity, after controlling for age, gender and vascular comorbidities. After further controlling for general cognitive performance, diffusion tensor imaging abnormalities of the cerebellum, hippocampus, thalamus and basal forebrain still remained associated with delirium incidence and severity. This study raises the intriguing possibility that structural dysconnectivity involving interhemispheric and fronto-thalamo-cerebellar networks, as well as microstructural changes of structures involved in limbic and memory functions predispose to delirium under the stress of surgery. While the diffusion tensor imaging abnormalities observed in the corpus callosum, cingulum, and temporal lobe likely constitute the neural substrate for the association between premorbid cognition, as measured by general cognitive performance, and postoperative delirium, the microstructural changes observed in the cerebellum, hippocampus, thalamus and basal forebrain seem to constitute a separate phenomenon that predisposes to postsurgical delirium independent of presurgical cognitive status. C1 [Cavallari, Michele; Guttmann, Charles R. G.; Meier, Dominik S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Ctr Neurol Imaging, Boston, MA 02115 USA. [Dai, Weiying; Callahan, Amy E.; Alsop, David C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02115 USA. [Dai, Weiying] SUNY Binghamton, Dept Comp Sci, Binghamton, NY USA. [Ngo, Long H.; Marcantonio, Edward R.; Inouye, Sharon K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Cambridge, MA 02138 USA. [Hshieh, Tammy T.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging, Cambridge, MA 02138 USA. [Hshieh, Tammy T.; Fong, Tamara G.; Schmitt, Eva; Inouye, Sharon K.] Hebrew SeniorLife, Inst Aging Res, Aging Brain Ctr, Boston, MA USA. [Fong, Tamara G.; Press, Daniel Z.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, 149 13th St, Charlestown, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neuroimaging, 149 13th St, Charlestown, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Disorders Unit, 149 13th St, Charlestown, MA USA. [Jones, Richard N.] Brown Univ, Warren Alpert Med Sch, Dept Psychiat, Providence, RI 02912 USA. [Jones, Richard N.] Brown Univ, Warren Alpert Med Sch, Dept Human Behav & Neurol, Providence, RI 02912 USA. RP Alsop, DC (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, Ansin 226,330 Brookline Ave, Boston, MA 02215 USA. EM dalsop@bidmc.harvard.edu RI Alsop, David/J-5764-2013; Jones, Richard/J-3488-2013 OI Alsop, David/0000-0002-8206-1995; Jones, Richard/0000-0002-1049-218X FU National Institute on Aging [P01AG031720, K07AG041835, K24AG035075]; NIH [AG000158] FX Supported by Grants No. P01AG031720 (S.K.I.) and K07AG041835 (S.K.I.) from the National Institute on Aging. T.T.H. is supported by a NIH funded T32 Training Grant (AG000158). E.R.M. is supported by K24AG035075 from the National Institute on Aging. S.K.I. holds the Milton and Shirley F. Levy Family Chair. The funding sources had no role in the design, conduct, or reporting of this study. NR 50 TC 3 Z9 3 U1 10 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD APR PY 2016 VL 139 BP 1282 EP 1294 DI 10.1093/brain/aww010 PN 4 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DJ5GN UT WOS:000374234900034 PM 26920674 ER PT J AU Werner, B Scott, JG Sottoriva, A Anderson, ARA Traulsen, A Altrock, PM AF Werner, Benjamin Scott, Jacob G. Sottoriva, Andrea Anderson, Alexander R. A. Traulsen, Arne Altrock, Philipp M. TI The Cancer Stem Cell Fraction in Hierarchically Organized Tumors Can Be Estimated Using Mathematical Modeling and Patient-Specific Treatment Trajectories SO CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; PATIENTS RECEIVING IMATINIB; 1ST-LINE TREATMENT; FOLLOW-UP; IN-VIVO; IDENTIFICATION; HETEROGENEITY; EVOLUTION; DYNAMICS; RESISTANCE AB Many tumors are hierarchically organized and driven by a subpopulation of tumor-initiating cells (TIC), or cancer stem cells. TICs are uniquely capable of recapitulating the tumor and are thought to be highly resistant to radio-and chemotherapy. Macroscopic patterns of tumor expansion before treatment and tumor regression during treatment are tied to the dynamics of TICs. Until now, the quantitative information about the fraction of TICs from macroscopic tumor burden trajectories could not be inferred. In this study, we generated a quantitative method based on a mathematical model that describes hierarchically organized tumor dynamics and patient-derived tumor burden information. The method identifies two characteristic equilibrium TIC regimes during expansion and regression. We show that tumor expansion and regression curves can be leveraged to infer estimates of the TIC fraction in individual patients at detection and after continued therapy. Furthermore, our method is parameter-free; it solely requires the knowledge of a patient's tumor burden over multiple time points to reveal microscopic properties of the malignancy. We demonstrate proof of concept in the case of chronic myeloid leukemia (CML), wherein our model recapitulated the clinical history of the disease in two independent patient cohorts. On the basis of patient-specific treatment responses in CML, we predict that after one year of targeted treatment, the fraction of TICs increases 100-fold and continues to increase up to 1,000-fold after 5 years of treatment. Our novel framework may significantly influence the implementation of personalized treatment strategies and has the potential for rapid translation into the clinic. C1 [Werner, Benjamin; Sottoriva, Andrea] Inst Canc Res, Ctr Evolut & Canc, London SW3 6JB, England. [Werner, Benjamin; Traulsen, Arne] Max Planck Inst Evolutionary Biol, Dept Evolutionary Theory, Plon, Germany. [Scott, Jacob G.; Anderson, Alexander R. A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Integrated Math Oncol Dept, Tampa, FL 33612 USA. [Altrock, Philipp M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Altrock, Philipp M.] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Altrock, Philipp M.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA. [Scott, Jacob G.] Univ Oxford, Wolfson Ctr Math Biol, Oxford, England. RP Altrock, PM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,CLSB 11007, Boston, MA 02215 USA. EM paltrock@jimmy.harvard.edu RI Traulsen, Arne/A-4955-2009 OI Traulsen, Arne/0000-0002-0669-5267 FU NCI NIH HHS [U54 CA143970, U54 CA113007] NR 51 TC 2 Z9 2 U1 79 U2 82 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 APR 1 PY 2016 VL 76 IS 7 BP 1705 EP 1713 DI 10.1158/0008-5472.CAN-15-2069 PG 9 WC Oncology SC Oncology GA DJ4IW UT WOS:000374169600007 PM 26833122 ER PT J AU Camp, NJ Lin, WY Bigelow, A Burghel, GJ Mosbruger, TL Parry, MA Waller, RG Rigas, SH Tai, PY Berrett, K Rajamanickam, V Cosby, R Brock, IW Jones, B Connley, D Sargent, R Wang, G Factor, RE Bernard, PS Cannon-Albright, L Knight, S Abo, R Werner, TL Reed, MWR Gertz, J Cox, A AF Camp, Nicola J. Lin, Wei-Yu Bigelow, Alex Burghel, George J. Mosbruger, Timothy L. Parry, Marina A. Waller, Rosalie G. Rigas, Sushilaben H. Tai, Pei-Yi Berrett, Kristofer Rajamanickam, Venkatesh Cosby, Rachel Brock, Ian W. Jones, Brandt Connley, Dan Sargent, Robert Wang, Guoying Factor, Rachel E. Bernard, Philip S. Cannon-Albright, Lisa Knight, Stacey Abo, Ryan Werner, Theresa L. Reed, Malcolm W. R. Gertz, Jason Cox, Angela TI Discordant Haplotype Sequencing Identifies Functional Variants at the 2q33 Breast Cancer Risk Locus SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; DISEASE; METAANALYSIS; DISCOVERY; FRAMEWORK; GENES; CASP8 AB The findings from genome-wide association studies hold enormous potential for novel insight into disease mechanisms. A major challenge in the field is to map these low-risk association signals to their underlying functional sequence variants (FSV). Simple sequence study designs are insufficient, as the vast numbers of statistically comparable variants and a limited knowledge of noncoding regulatory elements complicate prioritization. Furthermore, large sample sizes are typically required for adequate power to identify the initial association signals. One important question is whether similar sample sizes need to be sequenced to identify the FSVs. Here, we present a proof-of-principle example of an extreme discordant design to map FSVs within the 2q33 low-risk breast cancer locus. Our approach employed DNA sequencing of a small number of discordant haplotypes to efficiently identify candidate FSVs. Our results were consistent with those from a 2,000-fold larger, traditional imputation-based fine-mapping study. To prioritize further, we used expression-quantitative trait locus analysis of RNA sequencing from breast tissues, gene regulation annotations from the ENCODE consortium, and functional assays for differential enhancer activities. Notably, we implicate three regulatory variants at 2q33 that target CASP8 (rs3769823, rs3769821 in CASP8, and rs10197246 in ALS2CR12) as functionally relevant. We conclude that nested discordant haplotype sequencing is a promising approach to aid mapping of low-risk association loci. The ability to include more efficient sequencing designs into mapping efforts presents an opportunity for the field to capitalize on the potential of association loci and accelerate translation of association signals to their underlying FSVs. C1 [Camp, Nicola J.; Bigelow, Alex; Waller, Rosalie G.; Tai, Pei-Yi; Berrett, Kristofer; Rajamanickam, Venkatesh; Cosby, Rachel; Jones, Brandt; Sargent, Robert; Wang, Guoying; Factor, Rachel E.; Bernard, Philip S.; Cannon-Albright, Lisa; Knight, Stacey; Abo, Ryan; Werner, Theresa L.; Gertz, Jason] Univ Utah, Sch Med, Salt Lake City, UT USA. [Lin, Wei-Yu; Burghel, George J.; Parry, Marina A.; Rigas, Sushilaben H.; Brock, Ian W.; Connley, Dan; Reed, Malcolm W. R.; Cox, Angela] Univ Sheffield, Dept Oncol & Metab, Sheffield, S Yorkshire, England. [Bigelow, Alex] Univ Utah, Sch Comp, Salt Lake City, UT USA. [Mosbruger, Timothy L.] Univ Utah, Bioinformat Shared Resource, Salt Lake City, UT USA. [Lin, Wei-Yu] Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England. [Burghel, George J.] Manchester Ctr Genom Med, Manchester M13 9WL, Lancs, England. [Parry, Marina A.] Univ Manchester, Canc Res UK Manchester Inst, Manchester M20 4BX, Lancs, England. [Rigas, Sushilaben H.] Univ Bradford, Fac Life Sci, Sch Med Sci, Bradford BD7 1DP, W Yorkshire, England. [Knight, Stacey] Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT 84107 USA. [Abo, Ryan] Dana Farber Canc Inst, Boston, MA 02215 USA. [Reed, Malcolm W. R.] Univ Sussex, Brighton & Sussex Med Sch, Brighton BN1 9RH, E Sussex, England. RP Camp, NJ (reprint author), Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. EM nicola.camp@hci.utah.edu RI Lin, Wei-Yu/F-4505-2010; OI Lin, Wei-Yu/0000-0002-9267-7988; Waller, Rosalie/0000-0001-9437-8861; albright, lisa/0000-0003-2602-3668; Knight, Stacey/0000-0003-0092-7327 FU Cancer Research UK [A11292]; NCI NIH HHS [P30 CA042014, R01 CA163353]; Yorkshire Cancer Research [S295, S299, SPP060] NR 29 TC 1 Z9 1 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 APR 1 PY 2016 VL 76 IS 7 BP 1916 EP 1925 DI 10.1158/0008-5472.CAN-15-1629 PG 10 WC Oncology SC Oncology GA DJ4IW UT WOS:000374169600026 PM 26795348 ER PT J AU Huh, SJ Oh, H Peterson, MA Almendro, V Hu, R Bowden, M Lis, RL Cotter, MB Loda, M Barry, WT Polyak, K Tamimi, RM AF Huh, Sung Jin Oh, Hannah Peterson, Michael A. Almendro, Vanessa Hu, Rong Bowden, Michaela Lis, Rosina L. Cotter, Maura B. Loda, Massimo Barry, William T. Polyak, Kornelia Tamimi, Rulla M. TI The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women SO CANCER RESEARCH LA English DT Article ID DEPENDENT KINASE INHIBITOR; PROGESTERONE RECEPTORS; DUCTAL HYPERPLASIA; FEMALE BREAST; ESTROGEN; EXPRESSION; KI-67; P27(KIP1); MODELS; GROWTH AB The frequency and proliferative activity of tissue-specific stem and progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast cancer risk and the frequency of mammary epithelial cells expressing p27, estrogen receptor (ER), and Ki67 in normal breast tissue. We performed a nested case-control study of 302 women (69 breast cancer cases, 233 controls) who had been initially diagnosed with benign breast disease according to the Nurses' Health Studies. Immunofluorescence for p27, ER, and Ki67 was performed on tissue microarrays constructed from benign biopsies containing normal mammary epithelium and scored by computational image analysis. We found that the frequency of Ki67(+) cells was positively associated with breast cancer risk among premenopausal women [OR = 10.1, 95% confidence interval (CI) = 2.12-48.0]. Conversely, the frequency of ER+ or p27(+) cells was inversely, but not significantly, associated with subsequent breast cancer risk (ER+: OR = 0.70,95% CI, 0.33-1.50; p27(+): OR = 0.89, 95% CI, 0.45-1.75). Notably, high Ki67(+)/low p27(+) and high Ki67(+)/low ER+ cell frequencies were significantly associated with a 5-fold higher risk of breast cancer compared with low Ki67(+)/low p27(+) and low Ki67(+)/low ER+ cell frequencies, respectively, among premenopausal women (Ki67(hi)/p27(lo): OR = 5.08, 95% CI, 1.43-18.1; Ki67(hi)/ERlo: OR = 4.68,95% CI, 1.63-13.5). Taken together, our data suggest that the fraction of actively cycling cells in normal breast tissue may represent a marker for breast cancer risk assessment, which may therefore impact the frequency of screening procedures in at-risk women. C1 [Huh, Sung Jin; Peterson, Michael A.; Almendro, Vanessa; Bowden, Michaela; Lis, Rosina L.; Cotter, Maura B.; Loda, Massimo; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Huh, Sung Jin; Almendro, Vanessa; Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Huh, Sung Jin; Almendro, Vanessa; Hu, Rong; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Oh, Hannah; Hu, Rong; Tamimi, Rulla M.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Oh, Hannah; Hu, Rong; Tamimi, Rulla M.] Harvard Univ, Sch Med, Boston, MA USA. [Oh, Hannah; Hu, Rong; Tamimi, Rulla M.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Oh, Hannah; Hu, Rong] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Peterson, Michael A.; Bowden, Michaela; Lis, Rosina L.; Cotter, Maura B.; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Stem Cell Inst, Cambridge, MA USA. RP Tamimi, RM (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Tamimi, RM (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Tamimi, RM (reprint author), Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.; Polyak, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D740C, Boston, MA 02215 USA. EM Kornelia_Polyak@dfci.harvard.edu; rulla.tamimi@channing.harvard.edu FU NCI NIH HHS [P01 CA080111, F32 CA156991, P01 CA087969, R01 CA045745, R01 CA050385, T32 CA009001, UM1 CA176726, UM1 CA186107] NR 39 TC 3 Z9 3 U1 3 U2 5 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 APR 1 PY 2016 VL 76 IS 7 BP 1926 EP 1934 DI 10.1158/0008-5472.CAN-15-1927 PG 9 WC Oncology SC Oncology GA DJ4IW UT WOS:000374169600027 PM 26941287 ER PT J AU Lau, EF Weber, K Gramfort, A Hamalainen, MS Kuperberg, GR AF Lau, Ellen F. Weber, Kirsten Gramfort, Alexandre Haemaelaeinen, Matti S. Kuperberg, Gina R. TI Spatiotemporal Signatures of Lexical-Semantic Prediction SO CEREBRAL CORTEX LA English DT Article DE anterior temporal cortex; expectation; magnetoencephalography; N400; semantic ID EVENT-RELATED FMRI; ANTERIOR TEMPORAL CORTEX; BRAIN POTENTIAL ANALYSIS; LANGUAGE COMPREHENSION; RELATEDNESS PROPORTION; TIME-COURSE; SPEECH-PERCEPTION; FIELD POTENTIALS; WORD-FREQUENCY; FUNCTIONAL MRI AB Although there is broad agreement that top-down expectations can facilitate lexical-semantic processing, the mechanisms driving these effects are still unclear. In particular, while previous electroencephalography (EEG) research has demonstrated a reduction in the N400 response to words in a supportive context, it is often challenging to dissociate facilitation due to bottom-up spreading activation from facilitation due to top-down expectations. The goal of the current study was to specifically determine the cortical areas associated with facilitation due to top-down prediction, using magnetoencephalography (MEG) recordings supplemented by EEG and functional magnetic resonance imaging (fMRI) in a semantic priming paradigm. In order to modulate expectation processes while holding context constant, we manipulated the proportion of related pairs across 2 blocks (10 and 50% related). Event-related potential results demonstrated a larger N400 reduction when a related word was predicted, and MEG source localization of activity in this time-window (350-450 ms) localized the differential responses to left anterior temporal cortex. fMRI data from the same participants support the MEG localization, showing contextual facilitation in left anterior superior temporal gyrus for the high expectation block only. Together, these results provide strong evidence that facilitatory effects of lexical-semantic prediction on the electrophysiological response 350-450 ms postonset reflect modulation of activity in left anterior temporal cortex. C1 [Lau, Ellen F.; Weber, Kirsten; Kuperberg, Gina R.] Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. [Gramfort, Alexandre; Haemaelaeinen, Matti S.] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. [Gramfort, Alexandre; Haemaelaeinen, Matti S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lau, Ellen F.] Univ Maryland, Dept Linguist, College Pk, MD 20742 USA. [Lau, Ellen F.; Weber, Kirsten; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Gramfort, Alexandre] Telecom ParisTech, CNRS LTCI, Inst Mines Telecom, Dept Signal & Image Proc, Paris, France. [Haemaelaeinen, Matti S.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Lau, EF (reprint author), Univ Maryland, Dept Linguist, College Pk, MD 20742 USA. EM ellenlau@umd.edu FU National Institutes of Health [R01MH071635, F32HD063221, 5R01EB009048, P41RR14075]; Ellison Foundation FX This work was supported by the National Institutes of Health (grants R01MH071635 to G.R.K., F32HD063221 to E.L., and 5R01EB009048 and P41RR14075 to M.H.), as well as a grant from the Ellison Foundation to M.H. NR 84 TC 7 Z9 7 U1 6 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2016 VL 26 IS 4 BP 1377 EP 1387 DI 10.1093/cercor/bhu219 PG 11 WC Neurosciences SC Neurosciences & Neurology GA DJ5KM UT WOS:000374246700003 PM 25316341 ER PT J AU Hedden, T Schultz, AP Rieckmann, A Mormino, EC Johnson, KA Sperling, RA Buckner, RL AF Hedden, Trey Schultz, Aaron P. Rieckmann, Anna Mormino, Elizabeth C. Johnson, Keith A. Sperling, Reisa A. Buckner, Randy L. TI Multiple Brain Markers are Linked to Age-Related Variation in Cognition SO CEREBRAL CORTEX LA English DT Article DE aging; amyloid; executive function; memory; white matter ID NORMAL OLDER-ADULTS; WHITE-MATTER HYPERINTENSITIES; ALZHEIMERS-DISEASE; AMYLOID DEPOSITION; FUNCTIONAL CONNECTIVITY; EXECUTIVE FUNCTIONS; CEREBRAL-CORTEX; DECLINE; BURDEN; MEMORY AB Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only similar to 20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. C1 [Hedden, Trey; Schultz, Aaron P.; Rieckmann, Anna; Sperling, Reisa A.; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Schultz, Aaron P.; Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Schultz, Aaron P.; Sperling, Reisa A.; Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA USA. [Hedden, Trey; Johnson, Keith A.; Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA 02115 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Rieckmann, Anna] Umea Univ, Dept Radiat Sci, SE-90187 Umea, Sweden. RP Hedden, T (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM hedden@nmr.mgh.harvard.edu FU National Institute on Aging [P01 AG036694, P50 AG005134, R01 AG034556, R01 AG027435, K01 AG040197]; Alzheimer's Association [ZEN-10-174210]; Howard Hughes Medical Institute; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health [P41EB015896]; NIH [S10RR023401, S10RR019307, S10RR019254, S10RR023043] FX Funding was provided by National Institute on Aging grants P01 AG036694, P50 AG005134, R01 AG034556, R01 AG027435, and K01 AG040197; the Alzheimer's Association grant ZEN-10-174210, and by the Howard Hughes Medical Institute. 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, P41EB015896, 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 Program and/or High-End Instrumentation Grant Program; specifically, grant numbers S10RR023401, S10RR019307, S10RR019254, and S10RR023043. NR 66 TC 9 Z9 9 U1 4 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2016 VL 26 IS 4 BP 1388 EP 1400 DI 10.1093/cercor/bhu238 PG 13 WC Neurosciences SC Neurosciences & Neurology GA DJ5KM UT WOS:000374246700004 PM 25316342 ER PT J AU Furbass, F Herta, J Koren, J Westover, MB Hartmann, MM Gruber, A Baumgartner, C Kluge, T AF Fuerbass, Franz Herta, Johannes Koren, Johannes Westover, M. Brandon Hartmann, Manfred M. Gruber, Andreas Baumgartner, Christoph Kluge, Tilmann TI Monitoring burst suppression in critically ill patients: Multi-centric evaluation of a novel method SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Automatic detection; Burst suppression pattern; EEG; Real-time monitoring; Periodic pattern ID EEG; ANESTHESIA; PATTERN; ELECTROENCEPHALOGRAM; SEGMENTATION; TERMINOLOGY; HYPOTHERMIA; ISOFLURANE; BRAIN; DEPTH AB Objective: To develop a computational method to detect and quantify burst suppression patterns (BSP) in the EEGs of critical care patients. A multi-center validation study was performed to assess the detection performance of the method. Methods: The fully automatic method scans the EEG for discontinuous patterns and shows detected BSP and quantitative information on a trending display in real-time. The method is designed to work without setting any patient specific parameters and to be insensitive to EEG artifacts and periodic patterns. For validation a total of 3982 h of EEG from 88 patients were analyzed from three centers. Each EEG was annotated by two reviewers to assess the detection performance and the inter-rater agreement. Results: Average inter-rater agreement between pairs of reviewers was kappa = 0.69. On average 22% of the review segments included BSP. An average sensitivity of 90% and a specificity of 84% were measured on the consensus annotations of two reviewers. More than 95% of the periodic patterns in the EEGs were correctly suppressed. Conclusion: A fully automatic method to detect burst suppression patterns was assessed in a multi-center study. The method showed high sensitivity and specificity. Significance: Clinically applicable burst suppression detection method validated in a large multi-center study. (C) 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Fuerbass, Franz; Hartmann, Manfred M.; Kluge, Tilmann] AIT Austrian Inst Technol, Safety & Secur Dept, A-1220 Vienna, Austria. [Herta, Johannes; Gruber, Andreas] Med Univ Vienna, Dept Neurosurg, Vienna, Austria. [Koren, Johannes; Baumgartner, Christoph] Gen Hosp Hietzing, Neurol Ctr Rosenhuegel, Neurol Dept 2, Vienna, Austria. [Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Westover, M. Brandon] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Furbass, F (reprint author), AIT Austrian Inst Technol, Donau City Str 1, A-1220 Vienna, Austria. EM franz.fuerbass@ait.ac.at OI Furbass, Franz/0000-0002-6744-2802 FU ECSEL [324257]; national funding authority of Austria; national funding authority of Czech Republic; national funding authority of Germany; national funding authority of Italy; national funding authority of Netherlands; national funding authority of Spain; national funding authority of United Kingdom FX This work was partly done within the DeNeCoR project which received funding from the ECSEL Joint Undertaking under grant agreement No. 324257 and from the national funding authorities of Austria, Czech Republic, Germany, Italy, the Netherlands, Spain and the United Kingdom. NR 31 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD APR PY 2016 VL 127 IS 4 BP 2038 EP 2046 DI 10.1016/j.clinph.2016.02.001 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DJ4JS UT WOS:000374171800018 PM 26971487 ER PT J AU Arkilo, D Devinsky, O Mudigoudar, B Boronat, S Jennesson, M Sassower, K Vaou, OE Lerner, JT Jeste, SS Luchsinger, K Thibert, R AF Arkilo, Dimitrios Devinsky, Orrin Mudigoudar, Basanagoud Boronat, Susana Jennesson, Melanie Sassower, Kenneth Vaou, Okeanis Eleni Lerner, Jason T. Jeste, Shafali Spurling Luchsinger, Kadi Thibert, Ronald TI Electroencephalographic patterns during sleep in children with chromosome 15q11.2-13.1 duplications (Dup15q) SO EPILEPSY & BEHAVIOR LA English DT Article DE EEG patterns; Sleep; Dup15q syndrome; Children ID DEVELOPMENTAL DISORDER; 15Q DUPLICATION; 15Q11-Q13; SEIZURES; EPILEPSY AB Our objective was to define the EEG features during sleep of children with neurodevelopmental disorders due to copy number gains of 15q11-q13 (Dupl 5q). We retrospectively reviewed continuous EEG recordings of 42 children with Dupl5q (mean age: eight years, 32 with idicl5), and data collected included background activity, interictal epileptiform discharges, sleep organization, and ictal activity. Three patterns were recognized: Pattern 1: Alpha-delta sleep was noted in 14 children (33%), not associated with any clinical changes. Pattern 2: Electrical status epilepticus in sleep was noted in 15 children (35%), all diagnosed with treatment resistant epilepsy. Thirteen of the 15 children had clinical seizures. Pattern 3: Frequent bursts of high amplitude bifrontal predominant, paroxysmal fast activity (12-15 Hz) during non-REM sleep was noted in 15 children (35%). All 15 children had treatment-resistant epilepsy. This is the first report of electroencephalographic patterns during sleep of children with Dup15q reporting alpha delta rhythms, CSWS, and high amplitude fast frequencies. Alpha-delta rhythms are described in children with dysautonomia and/or mood disorders and CSWS in children with developmental regression. The significance of these findings in cognitive function and epilepsy for the children in our cohort needs to be determined with follow-up studies. (C) 2016 Elsevier Inc. All rights reserved. C1 [Arkilo, Dimitrios] PA Childrens Hosp & Clin Minnesota, Minnesota Epilepsy Grp, 225 Smith Ave N,St 201, St Paul, MN 55102 USA. [Devinsky, Orrin] NYU, Dept Neurol, NYU Langone Med Ctr, 240 East 38th St,20th Floor, New York, NY 10016 USA. [Mudigoudar, Basanagoud] Le Bonheur Childrens Hosp, Comprehens Epilepsy Program, 848 Adams Ave, Memphis, TN 38103 USA. [Mudigoudar, Basanagoud] Le Bonheur Childrens Hosp, Neurosci Ctr, 848 Adams Ave, Memphis, TN 38103 USA. [Boronat, Susana] Univ Autonoma Barcelona, Vall dHebron Hosp, Dept Pediat Neurol, P Vall dHebron 119-129, Barcelona 08035, Spain. [Jennesson, Melanie] CHU Reims, Amer Mem Hosp, Dept Pediat Neurol, 47 Rue Cognacq Jay, F-51100 Reims, France. [Sassower, Kenneth; Thibert, Ronald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 15 Parkman St,835, Boston, MA 02114 USA. [Vaou, Okeanis Eleni] Noran Neurol Clin, 2828 Chicago Ave S,200, Minneapolis, MN 55407 USA. [Lerner, Jason T.] Univ Calif Los Angeles, Mattel Childrens Hosp, Dept Pediat, 757 Westwood Plaza, Los Angeles, CA 90095 USA. [Jeste, Shafali Spurling] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. [Luchsinger, Kadi] Dup15Q Alliance, Fayetteville, NY 13066 USA. RP Arkilo, D (reprint author), PA Childrens Hosp & Clin Minnesota, Minnesota Epilepsy Grp, 225 Smith Ave N,St 201, St Paul, MN 55102 USA. EM arkdimi@hotmail.com; od4@nyu.edu; bmudigoudar@hotmail.com; susboronat@gmail.com; meljennesson@yahoo.fr; ksassower@mgh.harvard.edu; dimiark@hotmail.com; jlerner@mednet.ucla.edu; sjeste@mednet.ucla.edu; kadi.luchsinger@dup15q.org; rthibert@mgh.harvard.edu OI Devinsky, Orrin/0000-0003-0044-4632 FU UCB Pharma; GW pharmaceutical; Pfizer FX Dimitrios Arkilo receives funding for investigational trials from UCB Pharma, GW pharmaceutical, and Pfizer. Okeanis Eleni Vaou is on the speaker's bureau for Impax and Teva pharmaceuticals. Shafali Jeste is a consultant for Roche pharmaceuticals. Jason Lerner is a consultant for Bristol-Myers Squibb. The remaining authors have no disclosures or conflicts of interest. NR 15 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD APR PY 2016 VL 57 BP 133 EP 136 DI 10.1016/j.yebeh.2016.02.010 PN A PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA DJ5NW UT WOS:000374256700022 PM 26949155 ER PT J AU Salinsky, M Parko, K Rutecki, P Boudreau, E Storzbach, D AF Salinsky, Martin Parko, Karen Rutecki, Paul Boudreau, Eilis Storzbach, Daniel TI Attributing seizures to TBI: Validation of a brief patient questionnaire SO EPILEPSY & BEHAVIOR LA English DT Article DE Psychogenic seizures; Epilepsy; TBI; Veterans ID TRAUMATIC BRAIN-INJURY; PSYCHOGENIC NONEPILEPTIC SEIZURES; VETERANS AB Puipose: Traumatic brain injury (TBI) is an important cause of epilepsy and has also been associated with psychogenic nonepileptic seizures (PNES). We designed a brief questionnaire assessing patient beliefs regarding TBI as the cause of their seizures (Patient Seizure Etiology Questionnaire; PSEQ). This study reports content validity for the PSEQ Methods: Ninety Veterans undergoing comprehensive evaluation at 3 VA epilepsy centers completed the PSEQ a series of questions regarding possible causes for their seizures, including TB1. The PSEQ was scored as YES vs. NO for TBI as the proposed cause of seizures. For each patient, two expert reviewers independently completed a structured chart review to determine whether TBI was the proposed cause of seizures (n = 180 reviews). Kappa statistic was used to assess agreement between the PSEQ and each chart review and between the PSEQ and combined chart reviews where both reviewers agreed on a TBI seizure etiology. Results: The PSEQ scored higher overall rates for a TBI seizure etiology than did expert chart reviews (40% vs. 28%; p < 0.001). The PSEQ agreed with 82% of 180 independent chart reviews (sensitivity 88%; specificity 79%). Kappa statistic for agreement was 0.60. The two reviewers agreed on a probable TB1 seizure etiology for SR of chart reviews. The PSEQ sensitivity increased to 100% when both reviewers were in agreement. Conclusion: The PSEQ provides a direct, standardized measure of patient beliefs regarding TBlas the cause of their seizures and has moderate-substantial agreement with expert chart reviews. Published by Elsevier Inc. C1 [Salinsky, Martin; Boudreau, Eilis; Storzbach, Daniel] Portland VA Med Ctr, Portland, OR USA. [Salinsky, Martin; Boudreau, Eilis] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Parko, Karen] San Francisco VA Med Ctr, San Francisco, CA USA. [Rutecki, Paul] William S Middleton Vet Affairs Med Ctr, Madison, WI USA. RP Salinsky, M (reprint author), Portland VAMC Epilepsy Ctr Excellence, 3710 SW US Vet Hosp Rd P3ECOE, Portland, OR 97239 USA. EM Salinsky@ohsu.edu FU Department of Veterans Affairs [5101CX000721-04] FX The authors thank S. Chen FNP, R. Kotloski MD PhD, and C. Evrard FNP for their participation in this project. This work was supported by grant # 5101CX000721-04 from the Department of Veterans Affairs. NR 13 TC 0 Z9 0 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD APR PY 2016 VL 57 BP 141 EP 144 DI 10.1016/j.yebeh.2016.02.003 PN A PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA DJ5NW UT WOS:000374256700024 PM 26953843 ER PT J AU Pugh, MJ AF Pugh, Mary Jo TI Clinical decision rules for epilepsy care: The case for thinking big SO EPILEPSY & BEHAVIOR LA English DT Editorial Material ID PREDICTION; VALIDATION; GUIDELINES; MANAGEMENT; STANDARDS; MEDICINE; SEIZURE; ADULTS; RISK C1 [Pugh, Mary Jo] STVHCS, VA Epilepsy Ctr Excellence, San Antonio, TX USA. [Pugh, Mary Jo] UTHSCSA, Dept Epidemiol & Biostat, San Antonio, TX USA. [Pugh, Mary Jo] South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. RP Pugh, MJ (reprint author), STVHCS, VA Epilepsy Ctr Excellence, San Antonio, TX USA.; Pugh, MJ (reprint author), UTHSCSA, Dept Epidemiol & Biostat, San Antonio, TX USA.; Pugh, MJ (reprint author), South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Pughm@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763 FU NCCIH NIH HHS [1R01AT008422-01] NR 18 TC 0 Z9 0 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD APR PY 2016 VL 57 BP 220 EP 221 DI 10.1016/j.yebeh.2016.02.034 PN A PG 2 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA DJ5NW UT WOS:000374256700037 PM 26979764 ER PT J AU Schachter, SC AF Schachter, Steven C. TI Epilepsy and art: Windows into complexity and comorbidities SO EPILEPSY & BEHAVIOR LA English DT Article DE Art; Epilepsy; Seizure; Quality of life; Depression; Anxiety AB The views of artists with epilepsy as expressed through their art provide unique opportunities to gain understanding of the experiences of living with epilepsy and related comorbidities. This paper provides a glimpse into art collected from an international group of artists with epilepsy, focusing on ictal and postictal experiences, psychiatric comorbidities, and social aspects of epilepsy. The art serves to enhance understanding among clinicians and neuroscientists of what it means to have epilepsy as well as to reduce misunderstanding and stigma among the public. It may also inspire neuroscientists to further explore the underlying neurological basis to the rich tapestries of ictal, postictal, and interictal experiences of persons with epilepsy. (C) 2015 Elsevier Inc. All rights reserved. C1 [Schachter, Steven C.] Consortia Improving Med Innovat & Technol, Boston, MA USA. [Schachter, Steven C.] Massachusetts Gen Hosp, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. [Schachter, Steven C.] Harvard Univ, Sch Med, Boston, MA USA. [Schachter, Steven C.] 125 Nashua St,Room 3228, Boston, MA 02114 USA. RP Schachter, SC (reprint author), Consortia Improving Med Innovat & Technol, Boston, MA USA.; Schachter, SC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA.; Schachter, SC (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Schachter, SC (reprint author), 125 Nashua St,Room 3228, Boston, MA 02114 USA. EM sschacht@bidmc.harvard.edu NR 8 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD APR PY 2016 VL 57 BP 265 EP 269 DI 10.1016/j.yebeh.2015.12.024 PN B PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA DJ5OB UT WOS:000374257200010 PM 26775235 ER PT J AU Dullard, B Saunders, GH AF Dullard, Brittney Saunders, Gabrielle H. TI Documentation of Dual Sensory Impairment in Electronic Medical Records SO GERONTOLOGIST LA English DT Article DE Hearing impairment; Vision impairment; Interdisciplinary communication; Electronic medical records; Sensory disorders ID CONCURRENT HEARING; VISUAL IMPAIRMENT; VISION IMPAIRMENT; HEALTH-CARE; EXPERIENCES; PREVALENCE; PHYSICIANS; NEEDS AB Purpose of the Study: To examine the documentation of sensory impairment in the electronic medical records (EMRs) of Veterans with both hearing and vision losses (dual sensory impairment [DSI]). Design and Methods: A retrospective chart review of the EMRs of 20 patients with DSI was conducted. Providers' documentation of the presence of sensory impairment, the use of assistive technology during clinical appointments, and the content of notes mentioning communication issues were extracted from each chart note in the EMR for the prior 6 years. Results: Primary care providers documented DSI in 50% of EMRs, vision loss alone in 40%, and hearing loss alone in 10% of EMRs. Audiologists documented vision loss in 50% of cases, whereas ophthalmologists/optometrists documented hearing loss in 15% of cases. Examination of two selected cases illustrates that care can be compromised when providers do not take note of sensory impairments during planning and provision of clinical care. Implications: Sensory impairment is poorly documented by most providers in EMRs. This is alarming because vision and hearing affect patient-physician communication and the use of medical interventions. The results of this study raise awareness about the need to document the presence of sensory impairments and use the information when planning treatment for individuals with DSI. C1 [Dullard, Brittney] Univ Connecticut, Speech Language & Hearing Sci, Mansfield, CT 06250 USA. [Saunders, Gabrielle H.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. RP Dullard, B (reprint author), Univ Connecticut, Speech Language & Hearing Sci, Mansfield, CT 06250 USA. EM Brittney.Dullard@uconn.edu FU Portland VA Research Foundation; Department of Veterans Affairs Rehabilitation Research and Development [C9230C] FX This work was supported by a Portland VA Research Foundation Summer Fellowship and by the Department of Veterans Affairs Rehabilitation Research and Development (C9230C). NR 19 TC 2 Z9 2 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD APR PY 2016 VL 56 IS 2 BP 313 EP 317 DI 10.1093/geront/gnu032 PG 5 WC Gerontology SC Geriatrics & Gerontology GA DJ5BA UT WOS:000374220600017 PM 24846883 ER PT J AU Spiro, A Settersten, RA Aldwin, CM AF Spiro, Avron, III Settersten, Richard A. Aldwin, Carolyn M. TI Long-term Outcomes of Military Service in Aging and the Life Course: A Positive Re-envisioning (vol 56, pg 5, 2016) SO GERONTOLOGIST LA English DT Correction C1 [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02215 USA. [Settersten, Richard A.] Oregon State Univ, Coll Publ Hlth & Human Sci, Hallie E Ford Ctr Hlth Children & Families, Corvallis, OR 97331 USA. [Aldwin, Carolyn M.] Oregon State Univ, Coll Publ Hlth & Human Sci, Ctr Hlth Aging Res, Corvallis, OR 97331 USA. RP Spiro, A (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 151MAV, Boston, MA 02130 USA. EM aspiro3@bu.edu NR 1 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD APR PY 2016 VL 56 IS 2 BP 381 EP 381 DI 10.1093/geront/gnw038 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BA UT WOS:000374220600026 ER PT J AU Mukherjee, K Ishii, K Pillalamarri, V Kammin, T Atkin, JF Hickey, SE Xi, QCJ Zepeda, CJ Gusella, JF Talkowski, ME Morton, CC Maas, RL Liao, EC AF Mukherjee, Kusumika Ishii, Kana Pillalamarri, Vamsee Kammin, Tammy Atkin, Joan F. Hickey, Scott E. Xi, Qiongchao J. Zepeda, Cinthya J. Gusella, James F. Talkowski, Michael E. Morton, Cynthia C. Maas, Richard L. Liao, Eric C. TI Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis SO HUMAN MOLECULAR GENETICS LA English DT Article ID HIPPO PATHWAY; CLEFT-PALATE; F-ACTIN; CHROMOSOME REARRANGEMENTS; INSERTIONAL MUTAGENESIS; EMBRYONIC-DEVELOPMENT; FLUORESCENT PROTEIN; ZEBRAFISH PALATE; DROSOPHILA; MUTATIONS AB CAPZB is an actin-capping protein that caps the growing end of F-actin and modulates the cytoskeleton and tethers actin filaments to the Z-line of the sarcomere in muscles. Whole-genome sequencing was performed on a subject with micrognathia, cleft palate and hypotonia that harbored a de novo, balanced chromosomal translocation that disrupts the CAPZB gene. The function of capzb was analyzed in the zebrafish model. capzb(-/-) mutants exhibit both craniofacial and muscle defects that recapitulate the phenotypes observed in the human subject. Loss of capzb affects cell morphology, differentiation and neural crest migration. Differentiation of both myogenic stem cells and neural crest cells requires capzb. During palate morphogenesis, defective cranial neural crest cell migration in capzb(-/-) mutants results in loss of the median cell population, creating a cleft phenotype. capzb is also required for trunk neural crest migration, as evident from melanophores disorganization in capzb(-/-) mutants. In addition, capzb over-expression results in embryonic lethality. Therefore, proper capzb dosage is important during embryogenesis, and regulates both cell behavior and tissue morphogenesis. C1 [Mukherjee, Kusumika; Ishii, Kana; Liao, Eric C.] Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. [Mukherjee, Kusumika; Ishii, Kana; Liao, Eric C.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Pillalamarri, Vamsee; Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ishii, Kana] Nippon Med Sch, Dept Biochem & Mol Biol, Bunkyo Ku, Tokyo 1130022, Japan. [Kammin, Tammy; Zepeda, Cinthya J.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA. [Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Xi, Qiongchao J.; Maas, Richard L.] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. [Atkin, Joan F.; Hickey, Scott E.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA. [Atkin, Joan F.; Hickey, Scott E.] Nationwide Childrens Hosp, Div Mol & Human Genet, Columbus, OH 43205 USA. [Talkowski, Michael E.; Morton, Cynthia C.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Mukherjee, Kusumika; Ishii, Kana; Xi, Qiongchao J.; Gusella, James F.; Talkowski, Michael E.; Morton, Cynthia C.; Maas, Richard L.; Liao, Eric C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Liao, EC (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM cliao@partners.org FU National Institute of General Medical Sciences (NIGMS) [P01GM061354]; National Institute of Mental Health (NIMH) [R00MH095867]; March of Dimes; Charles Hood Foundation; National Institute of Dental and Craniofacial Research (NIDCR) [U01DE024443] FX This work was supported by the National Institute of General Medical Sciences (NIGMS) P01GM061354, the National Institute of Mental Health (NIMH) R00MH095867, the March of Dimes, the Charles Hood Foundation, and the National Institute of Dental and Craniofacial Research (NIDCR) U01DE024443. NR 73 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2016 VL 25 IS 7 BP 1255 EP 1270 DI 10.1093/hmg/ddw006 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DJ5FA UT WOS:000374231000001 PM 26758871 ER PT J AU Menze, BH Van Leemput, K Lashkari, D Riklin-Raviv, T Geremia, E Alberts, E Gruber, P Wegener, S Weber, MA Szekely, G Ayache, N Golland, P AF Menze, Bjoern H. Van Leemput, Koen Lashkari, Danial Riklin-Raviv, Tammy Geremia, Ezequiel Alberts, Esther Gruber, Philipp Wegener, Susanne Weber, Marc-Andre Szekely, Gabor Ayache, Nicholas Golland, Polina TI A Generative Probabilistic Model and Discriminative Extensions for Brain Lesion Segmentation- With Application to Tumor and Stroke SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Terms Medical diagnostic imaging; anatomical structure; tumors; image segmentation; object segmentation; Bayes methods ID DEFORMABLE REGISTRATION; OUTLIER DETECTION; BAYESIAN MODEL; RANDOM FORESTS; EM ALGORITHM; IMAGES; FRAMEWORK; GROWTH; INJURY AB We introduce a generative probabilistic model for segmentation of brain lesions in multi-dimensional images that generalizes the EM segmenter, a common approach for modelling brain images using Gaussian mixtures and a probabilistic tissue atlas that employs expectation-maximization (EM), to estimate the label map for a new image. Our model augments the probabilistic atlas of the healthy tissues with a latent atlas of the lesion. We derive an estimation algorithm with closed-form EM update equations. The method extracts a latent atlas prior distribution and the lesion posterior distributions jointly from the image data. It delineates lesion areas individually in each channel, allowing for differences in lesion appearance across modalities, an important feature of many brain tumor imaging sequences. We also propose discriminative model extensions to map the output of the generative model to arbitrary labels with semantic and biological meaning, such as "tumor core" or "fluid-filled structure", but without a one-to-one correspondence to the hypo- or hyper-intense lesion areas identified by the generative model. We test the approach in two image sets: the publicly available BRATS set of glioma patient scans, and multi modal brain images of patients with acute and subacute ischemic stroke. We find the generative model that has been designed for tumor lesions to generalize well to stroke images, and the extended discriminative-discriminative model to be one of the top ranking methods in the BRATS evaluation. C1 [Menze, Bjoern H.; Lashkari, Danial; Golland, Polina] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Menze, Bjoern H.; Geremia, Ezequiel; Ayache, Nicholas] INRIA Sophia Antipolis, Asclepios Res Project, F-06902 Sophia Antipolis, France. [Menze, Bjoern H.; Szekely, Gabor] ETH, Comp Vis Lab, CH-8092 Zurich, Switzerland. [Menze, Bjoern H.; Alberts, Esther] Tech Univ Munich, Inst Adv Study, D-80333 Munich, Germany. [Menze, Bjoern H.; Alberts, Esther] Tech Univ Munich, Dept Comp Sci, D-80333 Munich, Germany. [Van Leemput, Koen] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Van Leemput, Koen] Tech Univ Denmark, Dept Appl Math & Comp Sci, DK-2800 Lyngby, Denmark. [Riklin-Raviv, Tammy] Ben Gurion Univ Negev, Dept Elect & Comp Engn, IL-8410501 Beer Sheva, Israel. [Gruber, Philipp; Wegener, Susanne] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Weber, Marc-Andre] Univ Heidelberg Hosp, Dept Diagnost Radiol, D-69120 Heidelberg, Germany. RP Menze, BH (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.; Menze, BH (reprint author), INRIA Sophia Antipolis, Asclepios Res Project, F-06902 Sophia Antipolis, France.; Menze, BH (reprint author), ETH, Comp Vis Lab, CH-8092 Zurich, Switzerland.; Menze, BH (reprint author), Tech Univ Munich, Inst Adv Study, D-80333 Munich, Germany.; Menze, BH (reprint author), Tech Univ Munich, Dept Comp Sci, D-80333 Munich, Germany. EM bjoern.menze@tum.de OI Wegener, Susanne/0000-0003-4369-7023 FU National Alliance for Medical Image Analysis (NIH NIBIB NAMIC) [U54-EB005149]; Neuroimaging Analysis Center (NIH NIBIB NAC) [P41EB015902]; NIH NIBIB [R01EB013565]; Lundbeck Foundation [R141-2013-13117]; European Research Council through the ERC Advanced Grant MedYMA [2011-291080]; Swiss NSF project Computer Aided and Image Guided Medical Interventions (NCCR CO-ME); German Academy of Sciences Leopoldina [LPDS 2009-10]; Technische Universitat Munchen-Institute for Advanced Study - German Excellence Initiative [291763]; Technische Universitat Munchen-Institute for Advanced Study - European Union [291763]; Marie Curie COFUND program of the European Union FX This research was supported by the The National Alliance for Medical Image Analysis (NIH NIBIB NAMIC U54-EB005149), The Neuroimaging Analysis Center (NIH NIBIB NAC P41EB015902), NIH NIBIB (R01EB013565), the Lundbeck Foundation (R141-2013-13117),the European Research Council through the ERC Advanced Grant MedYMA 2011-291080 (on Biophysical Modeling and Analysis of Dynamic Medical Images), the Swiss NSF project Computer Aided and Image Guided Medical Interventions (NCCR CO-ME), the German Academy of Sciences Leopoldina (Fellowship Programme LPDS 2009-10), the Technische Universitat Munchen-Institute for Advanced Study (funded by the German Excellence Initiative and the European Union Seventh Framework Programme under grant agreement no. 291763), the Marie Curie COFUND program of the European Union (Rudolf Mossbauer Tenure-Track Professorship to BHM). Asterisk indicates corresponding author. NR 73 TC 2 Z9 2 U1 4 U2 12 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2016 VL 35 IS 4 BP 933 EP 946 DI 10.1109/TMI.2015.2502596 PG 14 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA DJ4HA UT WOS:000374164800001 PM 26599702 ER PT J AU Twyford, P Fried, S AF Twyford, Perry Fried, Shelley TI The Retinal Response to Sinusoidal Electrical Stimulation SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Electrical stimulation; retina; retinal prosthesis; sinusoidal ID GANGLION-CELLS; AMACRINE CELLS; RABBIT RETINA; MOUSE RETINA; PROSTHESIS; ACTIVATION; CALCIUM; MICROELECTRODE; DEGENERATION; THRESHOLDS AB Rectangular electrical pulses are the primary stimulus waveform used in retinal prosthetics as well as many other neural stimulation applications. Unfortunately, the utility of pulsatile stimuli is limited by the inability to avoid the activation of passing axons, which can result in the distortion of the spatial patterns of elicited neural activity. Because avoiding axons would likely improve clinical outcomes, the examination of alternate stimulus waveforms is warranted. Here, we studied the response of rabbit retinal ganglion cells (RGCs) to sinusoidal electrical stimulation applied at frequencies of 5, 10, 25, and 100 Hz. Targeted RGCs were restricted to 4 common types: OFF-Brisk Transient, OFF-Sustained, ON-Brisk Transient, and ON-Sustained. Interestingly, response patterns varied between different types; the most notable difference was the relatively weak response of ON-Sustained cells to low frequencies. Calculation of total spike counts per trial revealed that lower frequencies are more charge efficient than high frequencies. Finally, experiments utilizing synaptic blockers revealed that 5 and 10 Hz activate photoreceptors while 25 and 100 Hz activate RGCs. Taken together, our results suggest that while sinusoidal electrical stimulation may provide a useful research tool, its clinical utility may be limited. C1 [Twyford, Perry; Fried, Shelley] Massachusetts Gen Hosp, VA Boston Healthcare Syst, Boston, MA 02114 USA. [Twyford, Perry; Fried, Shelley] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Twyford, Perry; Fried, Shelley] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fried, S (reprint author), Massachusetts Gen Hosp, VA Boston Healthcare Syst, Boston, MA 02114 USA.; Fried, S (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.; Fried, S (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM fried.shelley@mgh.harvard.edu FU VA Boston Healthcare system [1I01RX000350-01A1]; NIH [1R01 EY019967-01] FX This research was supported by the VA Boston Healthcare system under Grant 1I01RX000350-01A1 as well as the NIH under Grant 1R01 EY019967-01. NR 49 TC 3 Z9 3 U1 2 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 EI 1558-0210 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD APR PY 2016 VL 24 IS 4 BP 413 EP 423 DI 10.1109/TNSRE.2015.2415811 PG 11 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA DJ5HX UT WOS:000374238600001 PM 25850091 ER PT J AU Bakhshaie, J Zvolensky, MJ Langdon, KJ Leventhal, AM Smits, JAJ Allan, N Schmidt, NB AF Bakhshaie, Jafar Zvolensky, Michael J. Langdon, Kirsten J. Leventhal, Adam M. Smits, Jasper A. J. Allan, Nicholas Schmidt, Norman B. TI Anxiety sensitivity class membership moderates the effects of pre-quit reduction in anxiety sensitivity on quit-day tobacco craving SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Anxiety sensitivity; Tobacco; Smoking; Craving; Withdrawal symptoms; Treatment ID FAGERSTROM TOLERANCE QUESTIONNAIRE; SMOKING-CESSATION TREATMENT; TREATMENT-SEEKING SMOKERS; FACTOR MIXTURE MODEL; NICOTINE DEPENDENCE; WITHDRAWAL SYMPTOMS; DEPRESSIVE SYMPTOMS; INITIAL VALIDATION; NEGATIVE AFFECT; PANIC DISORDER AB Background: Although anxiety sensitivity has been primarily conceptualized as a dimensional latent construct, empirical evidence suggests that it also maintains a latent class structure, reflecting low-, moderate-, and high-risk underlying classes. The present study sought to explore whether these anxiety sensitivity classes moderated the relations between the degree of pre-quit reductions in anxiety sensitivity and the severity of nicotine withdrawal symptoms and craving experienced on quit-day. Methods: Participants included 195 adult smokers (47% female; Mage =39.4) participating in a larger "anxiety sensitivity reduction-smoking cessation" intervention trial. Results: Anxiety sensitivity class significantly moderated relations between pre-quit reduction in anxiety sensitivity and quit-day craving. Specifically, smokers within the anxiety sensitivity high-risk class, who also demonstrated lesser pre-quit reductions in anxiety sensitivity, experienced the highest levels of craving on quit-day. Conclusions: These findings highlight the importance of 'high-risk' classes of anxiety sensitivity to better understand the experience of craving on quit day. 2016 Published by Elsevier Ltd. C1 [Bakhshaie, Jafar; Zvolensky, Michael J.] Univ Houston, Dept Psychol, Houston, TX 77204 USA. [Zvolensky, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. [Langdon, Kirsten J.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Langdon, Kirsten J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Leventhal, Adam M.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Leventhal, Adam M.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Smits, Jasper A. J.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Smits, Jasper A. J.] Univ Texas Austin, Mental Hlth Res Inst, Austin, TX 78712 USA. [Allan, Nicholas; Schmidt, Norman B.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. RP Bakhshaie, J (reprint author), Univ Houston, Anxiety & Hlth Res Lab, 104,126 Heyne Bldg, Houston, TX 77204 USA.; Bakhshaie, J (reprint author), Univ Houston, Subst Use Treatment Clin AHRL SUTC, 104,126 Heyne Bldg, Houston, TX 77204 USA. EM JBakhshaie@uh.edu FU National Institute of Mental Health [R01-MH076629-01A1] FX This work was supported by a National Institute of Mental Health grant awarded to Drs. Zvolensky and Schmidt (R01-MH076629-01A1). Please note that the content presented does not necessarily represent the official views of the National Institutes of Mental Health and that the funding sources had no other role other than financial support. NR 56 TC 1 Z9 1 U1 3 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD APR PY 2016 VL 39 BP 79 EP 87 DI 10.1016/j.janxdis.2016.02.009 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DJ4VS UT WOS:000374206800008 PM 26978668 ER PT J AU Becker, SJE Bruinsma, WE Guitton, TG van der Horst, CMAM Strackee, SD Ring, D AF Becker, Stephanie J. E. Bruinsma, Wendy E. Guitton, Thierry G. van der Horst, Chantal M. A. M. Strackee, Simon D. Ring, David CA Sci Variation Grp TI Interobserver Agreement of the Eaton-Glickel Classification for Trapeziometacarpal and Scaphotrapezial Arthrosis SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Classification agreement; interobserver reliability; osteoarthritis; scaphotrapezial arthrosis; trapeziometacarpal arthrosis ID THUMB CARPOMETACARPAL JOINT; DISTAL RADIUS FRACTURES; INTRAOBSERVER RELIABILITY; OSTEOARTHRITIS; PREVALENCE; ARTHRITIS; INTRARATER; DISABILITY; DISEASE AB Purpose To determine whether simplification of the Eaton-Glickel (E-G) classification of trapeziometacarpal (TMC) joint arthrosis (eliminating evaluation of the scaphotrapezial [ST] joint) and information about the patient's symptoms and examination influence interobserver reliability. We also tested the null hypotheses that no patient and/or surgeon factors affect radiographic rating of TMC joint arthrosis and that no surgeon factors affect the radiographic rating of ST joint arthrosis. Methods In an on-line survey, 92 hand surgeons rated TMC joint arthrosis and ST joint arthrosis separately on 30 radiographs (Robert, true lateral, and oblique views) according to the (modified) E-G classification. We randomly assigned 42 observers to review radiographs alone and also informed 50 of the patient's symptoms and examination. Information about symptoms and examination was randomized. Interobserver reliability was determined with the s* statistic. Because of the hierarchical data structure, cross-classified ordinal multilevel regression analyses were performed to identify factors associated with the severity of arthrosis. Results Shortening the E-G classification to the first 3 stages significantly improved the interobserver reliability, which approached substantial agreement. Providing clinical information to observers marginally improved interobserver reliability. Factors associated with a lower E-G stage for TMC joint arthrosis, among observers who rated the severity of TMC joint arthrosis based on radiographs and clinical information, included female surgeon, practice setting, supervising surgical trainees in the operating room, self-reported number of patients with TMC joint arthrosis typically treated annually, male patient, higher patient age, pain limiting daily activities, and shoulder sign. A self-reported larger number of patients with TMC joint arthrosis treated annually was the only variable associated with a higher modified E-G classification to rate ST joint arthrosis. Conclusions Our findings suggest that simpler classifications that focus on a single anatomical area are reliable and that surgeon and patient factors can bias interpretation of objective pathophysiology such as radiographic findings. Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved. C1 [Becker, Stephanie J. E.; van der Horst, Chantal M. A. M.; Strackee, Simon D.] Univ Amsterdam, Acad Med Ctr, Dept Plast Reconstruct & Hand Surg, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Guitton, Thierry G.] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, Orthopaed Res Ctr Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Bruinsma, Wendy E.] Univ Groningen, Univ Med Ctr Groningen, Dept Surg, Groningen, Netherlands. [Becker, Stephanie J. E.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879; Soong, Maximillian/0000-0003-0333-8181; Bainbridge, Lionel/0000-0001-7987-2845 FU Anna Foundation\NOREF; Genootschap Noorthey; Stichting Fonds Doctor Catharine van Tussenbroek; Stichting Vreedefonds, The Netherlands FX S.J.E.B. is supported by Dutch research grants from the Anna Foundation vertical bar NOREF, Genootschap Noorthey, Stichting Fonds Doctor Catharine van Tussenbroek, and Stichting Vreedefonds, The Netherlands, for scientific research. The authors thank Nan van Geloven, PhD, and Rebecca Holman, biostatisticians at the Clinical Research Unit of the Academic Medical Center in Amsterdam, for help with the statistical analysis of this study. NR 29 TC 1 Z9 1 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2016 VL 41 IS 4 BP 532 EP 540 DI 10.1016/j.jhsa.2015.12.028 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DJ5VQ UT WOS:000374278600005 PM 26826947 ER PT J AU del Pino, JG Calderon, SAL Chebib, I Jupiter, JB AF Gonzalez del Pino, Juan Lozano Calderon, Santiago A. Chebib, Ivan Jupiter, Jesse B. TI Intralesional Versus Wide Resection of Low-Grade Chondrosarcomas of the Hand SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article ID BENIGN SOLITARY ENCHONDROMA; LONG BONES; I CHONDROSARCOMA; CARTILAGINOUS TUMORS; SURGICAL-MANAGEMENT; FOLLOW-UP; CURETTAGE; FEET; CLASSIFICATION; CRYOSURGERY AB Purpose To report our experience with intralesional curettage (resection with positive margins) and amputation (resection with negative margins) of low-grade chondrosarcomas (LCS) of the hand. Materials and methods Skeletally mature patients treated surgically for LCS of the hand at our institutions were reviewed. Demographics and oncological history were collected. Results of the entire cohort and by treatment modality were analyzed radiographically, functionally (strength, Disabilities of the Arm, Shoulder, and Hand measure), cosmetically, and oncologically (recurrence, Musculoskeletal Tumor Society score, metastasis, and mortality rates). C1 [Gonzalez del Pino, Juan] Hosp Univ Santa Cristina, Dept Orthopaed Surg, Div Hand Surg, Madrid, Spain. [Lozano Calderon, Santiago A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp,Dept Orthopaed Surg, Div Musculoskeletal Oncol,Sch Med, Boston, MA 02115 USA. [Chebib, Ivan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02115 USA. [Jupiter, Jesse B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Div Hand Surg, Boston, MA 02115 USA. RP Calderon, SAL (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Div Musculoskeletal Oncol, YAW 3B Suite 3200,55 Fruit St, Boston, MA 02114 USA. EM slozanocalderon@mgh.harvard.edu NR 50 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2016 VL 41 IS 4 BP 541 EP 549 DI 10.1016/j.jhsa.2015.12.025 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DJ5VQ UT WOS:000374278600006 ER PT J AU Van den Abbeele, AD Krajewski, KM Tirumani, SH Fennessy, FM DiPiro, PJ Nguyen, QD Harris, GJ Jacene, HA Lefever, G Ramaiya, NH AF Van den Abbeele, Annick D. Krajewski, Katherine M. Tirumani, Sree Harsha Fennessy, Fiona M. DiPiro, Pamela J. Quang-De Nguyen Harris, Gordon J. Jacene, Heather A. Lefever, Greg Ramaiya, Nikhil H. TI Cancer Imaging at the Crossroads of Precision Medicine: Perspective From an Academic Imaging Department in a Comprehensive Cancer Center SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Cancer imaging; precision medicine; disease-centric; multidisciplinary; training ID COSTS; CARE AB The authors propose one possible vision for the transformative role that cancer imaging in an academic setting can play in the current era of personalized and precision medicine by sharing a conceptual model that is based on experience and lessons learned designing a multidisciplinary, integrated clinical and research practice at their institution. The authors' practice and focus are disease-centric rather than imaging centric. A "wall-less" infrastructure has been developed, with bidirectional integration of preclinical and clinical cancer imaging research platforms, enabling rapid translation of novel cancer drugs from discovery to clinical trial evaluation. The talents and expertise of medical professionals, scientists, and staff members have been coordinated in a horizontal and vertical fashion through the creation of Cancer Imaging Consultation Services and the "Adopt-a-Radiologist" campaign. Subspecialized imaging consultation services at the hub of an outpatient cancer center facilitate patient decision support and management at the point of care. The Adopt-a-Radiologist campaign has led to the creation of a novel generation of imaging clinician-scientists, fostered new collaborations, increased clinical and academic productivity, and improved employee satisfaction. Translational cancer research is supported, with a focus on early in vivo testing of novel cancer drugs, co-clinical trials, and longitudinal tumor imaging metrics through the imaging research core laboratory. Finally, a dedicated cancer imaging fellowship has been developed, promoting the future generation of cancer imaging specialists as multidisciplinary, multitalented professionals who are trained to effectively communicate with clinical colleagues and positively influence patient care. C1 [Van den Abbeele, Annick D.; Krajewski, Katherine M.; Tirumani, Sree Harsha; Fennessy, Fiona M.; DiPiro, Pamela J.; Quang-De Nguyen; Jacene, Heather A.; Lefever, Greg; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave,DL147-C, Boston, MA 02215 USA. [Van den Abbeele, Annick D.; Krajewski, Katherine M.; Tirumani, Sree Harsha; Fennessy, Fiona M.; DiPiro, Pamela J.; Jacene, Heather A.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Van den Abbeele, Annick D.; Quang-De Nguyen] Dana Farber Canc Inst, Ctr Biomed Imaging Oncol, Boston, MA 02215 USA. [Van den Abbeele, Annick D.; Harris, Gordon J.] Dana Farber Harvard Canc Ctr, Tumor Imaging Metr Core, Boston, MA USA. [Harris, Gordon J.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Krajewski, KM (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave,DL147-C, Boston, MA 02215 USA. EM kmkrajewski@partners.org FU National Cancer Institute; Massachusetts Life Sciences Center; DFCI FX The authors acknowledge and recognize the exceptional work and contributions provided by Leonid Syrkin, Amanda Abbott, Kin Wong, and Lisa Higgins in collecting, analyzing, and presenting the data and the invaluable assistance they consistently provide to our clinical and research teams. The authors also recognize the collegiality, guidance, and collaboration that numerous colleagues and collaborators have given them over the years, including the Dana-Farber Cancer Institute (DFCI) president and CEO, Edward J. Benz, MD, and the DFCI chief scientific officer, Barrett J. Rollins, MD, PhD; the chair of the Brigham and Women's Hospital Department of Radiology, Steven S. Seltzer, MD; the DFCI Disease Center leaders and members of their team; past (Kitt Shaffer, MD, Ramsey Badawi, PhD, and Jeffrey Yap, PhD) and current Department of Imaging staff members, technologists, nurses, and faculty members; previous LFIC directors (Andrew Kung, MD, and Nancy Kohl, PhD) and current members of the LFIC team; the Experimental Therapeutics Center team, led by Prafulla Gokhale, PhD; the TIMC past and current staff and faculty members; and Kwok Wong, MD, Paul T. Kirschmeier, PhD, and Jessie M. English, PhD, from the Belfer Institute. The authors apologize for not being able to name everyone. The authors also could not have accomplished what they did without the extraordinary generosity from their benefactor, the Lurie family, and without the help provided by members of the DFCI Development office. The authors also recognize the scientific and clinical collaboration with their pharmaceutical industry collaborators, the Institutional Strategic Centers' support from the DFCI, and the grant support from the National Cancer Institute and the Massachusetts Life Sciences Center. The authors thank Steven S. Seltzer, MD, Barrett J. Rollins, MD, PhD, Eva Guinan, MD, James S. Adelstein,.MD, PhD, and Barbara J. McNeil, MD, PhD, for their review of the manuscript, insightful comments, and suggestions. Most of all, the authors are deeply grateful and thankful for the patients and their families, who have given so much of themselves for the scientific and medical advancements of cancer research. NR 7 TC 2 Z9 2 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2016 VL 13 IS 4 BP 365 EP 371 DI 10.1016/j.jacr.2015.11.002 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ5UZ UT WOS:000374276900007 PM 26774886 ER PT J AU Harvey, SC Di Carlo, PA Lee, B Obadina, E Sippo, D Mullen, L AF Harvey, Susan C. Di Carlo, Phillip A. Lee, Bonmyong Obadina, Eniola Sippo, Dorothy Mullen, Lisa TI An Abbreviated Protocol for High-Risk Screening Breast MRI Saves Time and Resources SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Breast imaging; breast MRI; breast cancer; high-risk screening ID MAMMOGRAPHICALLY DENSE BREASTS; PROOF-OF-CONCEPT; DIGITAL MAMMOGRAPHY; CANCER-DETECTION; WOMEN; US; TOMOSYNTHESIS; ULTRASOUND; ACCURACY; FAILURE AB Purpose: To review the ability of an abbreviated, high-risk, screening, breast MRI protocol to detect cancer and save resources. Methods: High-risk screening breast MR images were reviewed, from both an abbreviated protocol and a full diagnostic protocol. Differences in cancer detection, scanner utilization, interpretation times, and need for additional imaging were recorded in an integrated data form, and reviewed and compared. Results: A total of 568 MRI cases were reviewed, with the abbreviated and full protocols. No difference was found in the number of cancers detected. Scan times were decreased by 18.8 minutes per case, for a total of 10,678 minutes (178 hours). Interpretation time, on average, was 1.55 minutes for the abbreviated protocol, compared with 6.43 minutes for the full protocol. Review of the full protocol led to a significant change in the final BI-RADS (R) assessment in 12 of 568 (2.1%) cases. Conclusions: Abbreviated MRI is as effective as full-protocol MRI for demonstration of cancers in the high-risk screening setting, with only 12 (2.1 %) cases recommended for additional MRI evaluation. The efficiency and resource savings of an abbreviated protocol would be significant, and would allow for opportunities to provide MRI for additional patients, as well as improved radiologist time management and workflow, with the potential to add real-time MRI interpretation or double reading. C1 [Harvey, Susan C.; Di Carlo, Phillip A.; Lee, Bonmyong; Obadina, Eniola; Mullen, Lisa] Johns Hopkins Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 601 North Caroline St,Room 4120E, Baltimore, MD 21287 USA. [Sippo, Dorothy] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Harvey, SC (reprint author), Johns Hopkins Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 601 North Caroline St,Room 4120E, Baltimore, MD 21287 USA. EM sharvey7@jhmi.edu NR 35 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2016 VL 13 IS 4 BP 374 EP 380 DI 10.1016/j.jacr.2015.08.015 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ5UZ UT WOS:000374276900009 PM 26521970 ER PT J AU Glover, M Patel, TY AF Glover, McKinley Patel, Tirath Y. TI The Radiology Fellowship Arms Race Cannot Be Won SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID EDUCATION; PROGRAM C1 [Glover, McKinley] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Blake 258, Boston, MA 02114 USA. [Patel, Tirath Y.] Univ Toledo, Med Ctr, Dept Radiol, 2801 W Bancroft St, Toledo, OH 43606 USA. RP Glover, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Blake 258, Boston, MA 02114 USA. EM mckinley.glover@mgh.harvard.edu NR 30 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2016 VL 13 IS 4 BP 461 EP 464 DI 10.1016/j.jacr.2015.11.025 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ5UZ UT WOS:000374276900025 PM 26810635 ER PT J AU Misono, AS Saini, S Prabhakar, AM AF Misono, Alexander S. Saini, Sanjay Prabhakar, Anand M. TI Radiology Jobs: Uncovering Hidden and Not-So-Hidden Opportunities From the ACR Jobs Board SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Radiologist; employment; job market ID MARKET AB Purpose: The radiology job market remains daunting. Trainees choosing fellowships benefit from understanding employers' likely future needs. Radiology practices may similarly refine recruiting practices. This study quantitatively analyzes the current radiology job landscape. Methods: Job postings on the ACR Career Center online portal between June 2014 and June 2015 were reviewed. As entries are frequently added and removed, posts were manually collected weekly. Postings were recorded in a database and included date, practice, location, specialty/subspecialty, job type, years of experience, salary, and job description. The database was analyzed to characterize employer needs, salary, partnership track availability, and job availability by geography. Results: A total of 1,778 jobs were posted during the study period. Of these, 1,529 (86.0%) were diagnostic; 240 (13.5%) were interventional; and 9 (0.5%) were administrative. Most jobs were in private practice (75.7%), compared with academic (16.3%) and other (7.9%). Although many did not require a specific specialty (46%), the most-frequent needs were breast (17%), neuroradiology (11%), musculoskeletal (8%), and body (7%). Of non-breast-imaging jobs, roughly 30% indicated an interest in breast-imaging skills. A minority (13%) requested prior experience of greater than 1 year, with some seeking 7-10 years of experience. Although most (87%) were full-time positions, part-time, temporary, and contractor roles were described in the remaining 13%. Salary data were rarely reported (7%), with a range of $98,967-$1,000,000. The most jobs were based in California (11%); New York (7%); Pennsylvania (7%); and Illinois (6%). However, when indexed per million population, the highest job rates were in Nevada (14.1); Washington DC (13.7); Hawaii (13.4); Montana (9.8); and Pennsylvania (9.1). Roughly 31% of postings described partnership tracks, with the highest rates in New England (58%), the Pacific Northwest (56%), the Midwest (40%), and Southern (40%) regions; the lowest were in the Mountain (26%), Mid-Atlantic (25%), and Southwest (21%) regions. Conclusions: Most radiology jobs remain in private practice general radiology. Breast, neuroradiology, and musculoskeletal radiology were most frequently desired among areas of subspecialty training. Advertised partnership tracks were less common and varied widely geographically. C1 [Misono, Alexander S.; Saini, Sanjay] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Prabhakar, Anand M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Cardiovasc Imaging, 55 Fruit St,Gray 2, Boston, MA 02114 USA. RP Prabhakar, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Cardiovasc Imaging, 55 Fruit St,Gray 2, Boston, MA 02114 USA. EM aprabhakar@mgh.harvard.edu NR 6 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2016 VL 13 IS 4 BP 471 EP 476 DI 10.1016/j.jacr.2015.09.027 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ5UZ UT WOS:000374276900027 PM 26706192 ER PT J AU Loftie-Eaton, W Yano, H Burleigh, S Simmons, RS Hughes, JM Rogers, LM Hunter, SS Settles, ML Forney, LJ Ponciano, JM Top, EM AF Loftie-Eaton, Wesley Yano, Hirokazu Burleigh, Stephen Simmons, Ryan S. Hughes, Julie M. Rogers, Linda M. Hunter, Samuel S. Settles, Matthew L. Forney, Larry J. Ponciano, Jose M. Top, Eva M. TI Evolutionary Paths That Expand Plasmid Host-Range: Implications for Spread of Antibiotic Resistance SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE antibiotic resistance; horizontal gene transfer; broad host range plasmid; Pseudomonas; epistasis; toxin-antitoxin; resolvase; transposon; experimental evolution ID PROGRAMMED CELL-DEATH; BACTERIAL PLASMIDS; MODEL SELECTION; ESCHERICHIA-COLI; PROMISCUOUS PLASMID; CONJUGATIVE PLASMID; POPULATION BIOLOGY; REPLICATION; MAINTENANCE; STABILITY AB The World Health Organization has declared the emergence of antibiotic resistance to be a global threat to human health. Broad-host-range plasmids have a key role in causing this health crisis because they transfer multiple resistance genes to a wide range of bacteria. To limit the spread of antibiotic resistance, we need to gain insight into the mechanisms by which the host range of plasmids evolves. Although initially unstable plasmids have been shown to improve their persistence through evolution of the plasmid, the host, or both, the means by which this occurs are poorly understood. Here, we sought to identify the underlying genetic basis of expanded plasmid host-range and increased persistence of an antibiotic resistance plasmid using a combined experimental-modeling approach that included whole-genome resequencing, molecular genetics and a plasmid population dynamics model. In nine of the ten previously evolved clones, changes in host and plasmid each slightly improved plasmid persistence, but their combination resulted in a much larger improvement, which indicated positive epistasis. The only genetic change in the plasmid was the acquisition of a transposable element from a plasmid native to the Pseudomonas host used in these studies. The analysis of genetic deletions showed that the critical genes on this transposon encode a putative toxin-antitoxin (TA) and a cointegrate resolution system. As evolved plasmids were able to persist longer in multiple na < ve hosts, acquisition of this transposon also expanded the plasmid's host range, which has important implications for the spread of antibiotic resistance. C1 [Loftie-Eaton, Wesley; Yano, Hirokazu; Burleigh, Stephen; Simmons, Ryan S.; Hughes, Julie M.; Rogers, Linda M.; Settles, Matthew L.; Forney, Larry J.; Top, Eva M.] Univ Idaho, Dept Biol Sci, Moscow, ID 83843 USA. [Loftie-Eaton, Wesley; Yano, Hirokazu; Hughes, Julie M.; Rogers, Linda M.; Hunter, Samuel S.; Settles, Matthew L.; Forney, Larry J.; Top, Eva M.] Univ Idaho, Inst Bioinformat & Evolutionary Studies IBEST, Moscow, ID 83843 USA. [Ponciano, Jose M.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA. [Yano, Hirokazu] Univ Tokyo, Grad Sch Frontier Sci, Minato Ku, Tokyo, Japan. [Yano, Hirokazu] Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo, Japan. [Burleigh, Stephen] Seattle Childrens Res Inst, Seattle, WA USA. [Simmons, Ryan S.] Oregon State Univ, Dept Microbiol, Corvallis, OR 97331 USA. [Hughes, Julie M.] White Pine Charter Sch, 2959 John Adams Pkwy, Ammon, ID USA. [Hunter, Samuel S.] Dana Farber Canc Inst, CCGD, Boston, MA 02115 USA. [Settles, Matthew L.] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. RP Top, EM (reprint author), Univ Idaho, Dept Biol Sci, Moscow, ID 83843 USA.; Top, EM (reprint author), Univ Idaho, Inst Bioinformat & Evolutionary Studies IBEST, Moscow, ID 83843 USA.; Ponciano, JM (reprint author), Univ Florida, Dept Biol, Gainesville, FL 32611 USA. EM josemi@ufl.edu; evatop@uidaho.edu RI Settles, Matthew/F-2031-2011; OI Settles, Matthew/0000-0002-3424-1086; Ponciano, Jose Miguel/0000-0001-8457-7840; Yano, Hirokazu/0000-0001-5144-3459 FU National Institute of Allergy and Infectious Diseases at the National Institute of Health [R01 AI084918]; National Institute of General Medical Sciences at the National Institute of Health [P20RR16448, P20GM103397]; National Science Foundation BEACON Centre for the Study of Evolution in Action [DBI-0939454]; Department of Biological Sciences, University of Idaho FX This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institute of Health (grant number R01 AI084918), National Institute of General Medical Sciences at the National Institute of Health (COBRE grants P20RR16448 to and P20GM103397); the National Science Foundation BEACON Centre for the Study of Evolution in Action (grant number DBI-0939454); and Undergraduate Research Grants to J.M.H., R.S.S., and S.B. from the Department of Biological Sciences, University of Idaho. The authors are grateful to the staff of the IBEST Genomics Core facility for the genome resequencing work and to the National BioResource Project (NBRP) of National Institute of Genetics (NIG; Japan) for providing Escherichia coli BW25113. NR 63 TC 4 Z9 4 U1 21 U2 41 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 EI 1537-1719 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD APR PY 2016 VL 33 IS 4 BP 885 EP 897 DI 10.1093/molbev/msv339 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA DJ5DJ UT WOS:000374226700003 PM 26668183 ER PT J AU Felker, P Bunch, R Leung, AM AF Felker, Peter Bunch, Ronald Leung, Angela M. TI Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in brassica vegetables, and associated potential risk for hypothyroidism SO NUTRITION REVIEWS LA English DT Review DE broccoli; Chinese cabbage; glucosinolate; glucoraphanin; indole; kale; phase II enzymes ID PHASE-II ENZYMES; BRUSSELS-SPROUTS; FROZEN BROCCOLI; THIOL OXIDATION; FRESH BROCCOLI; BREAST-CANCER; IN-VIVO; SULFORAPHANE; ISOTHIOCYANATES; EXPRESSION AB Brassica vegetables are common components of the diet and have beneficial as well as potentially adverse health effects. Following enzymatic breakdown, some glucosinolates in brassica vegetables produce sulforaphane, phenethyl, and indolylic isothiocyanates that possess anticarcinogenic activity. In contrast, progoitrin and indolylic glucosinolates degrade to goitrin and thiocyanate, respectively, and may decrease thyroid hormone production. Radioiodine uptake to the thyroid is inhibited by 194 mu mol of goitrin, but not by 77 mu mol of goitrin. Collards, Brussels sprouts, and some Russian kale (Brassica napus) contain sufficient goitrin to potentially decrease iodine uptake by the thyroid. However, turnip tops, commercial broccoli, broccoli rabe, and kale belonging to Brassica oleracae contain less than 10 mu mol of goitrin per 100-g serving and can be considered of minimal risk. Using sulforaphane plasma levels following glucoraphanin ingestion as a surrogate for thiocyanate plasma concentrations after indole glucosinolate ingestion, the maximum thiocyanate contribution from indole glucosinolate degradation is estimated to be 10 mu M, which is significantly lower than background plasma thiocyanate concentrations (40-69 mu M). Thiocyanate generated from consumption of indole glucosinolate can be assumed to have minimal adverse risks for thyroid health. C1 [Felker, Peter; Bunch, Ronald] DArrigo Bros Co Calif, 21777 Harris Rd, Salinas, CA 93908 USA. [Leung, Angela M.] VA Greater Angeles Healthcare Syst, Div Endocrinol, Los Angeles, CA USA. [Leung, Angela M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol, Los Angeles, CA 90095 USA. RP Felker, P (reprint author), DArrigo Bros Co Calif, 21777 Harris Rd, Salinas, CA 93908 USA. EM Peter.Felker@darrigo.com FU National Institutes of Health [K23HD068552] FX The study was supported in part by National Institutes of Health K23HD068552 (A.M.L.). NR 66 TC 1 Z9 1 U1 7 U2 19 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0029-6643 EI 1753-4887 J9 NUTR REV JI Nutr. Rev. PD APR PY 2016 VL 74 IS 4 BP 248 EP 258 DI 10.1093/nutrit/nuv110 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DJ4OD UT WOS:000374184800003 PM 26946249 ER PT J AU Nipp, RD Lee, H Powell, E Birrer, NE Poles, E Finkelstein, D Winkfield, K Percac-Lima, S Chabner, B Moy, B AF Nipp, Ryan D. Lee, Hang Powell, Elizabeth Birrer, Nicole E. Poles, Emily Finkelstein, Daniel Winkfield, Karen Percac-Lima, Sanja Chabner, Bruce Moy, Beverly TI Financial Burden of Cancer Clinical Trial Participation and the Impact of a Cancer Care Equity Program SO ONCOLOGIST LA English DT Article DE Cost of illness; Health care costs; Clinical trial; Financial support; Quality of life ID BREAST-CANCER; SELF-EFFICACY; HEALTH-CARE; BARRIERS; ENROLLMENT; EXPERIENCE; COSTS; PREPAREDNESS; POPULATIONS; PREDICTORS AB Introduction. Cancer clinical trial (CT) participation rates are low and financial barriers likely play a role. We implemented a cancer care equity program(CCEP) to address financial burden associated with trial participation. We sought to examine the impact of the CCEP on CT enrollment and to assess barriers to participation. Methods. We used an interrupted time series design to determine trends in CT enrollment before and after CCEP implementation. Linear regression models compared trial enrollment before and after the CCEP. We also compared patient characteristics before and after the CCEP and between CCEP and non-CCEP participants. We surveyed CCEP and non-CCEP participants to compare pre-enrollment financial barriers. Results. After accounting for increased trial availability and the trends in accrual for prior years, we found that enrollment increased after CCEP implementation (18.97 participants per month greater than expected; p<.001). A greater proportion of CCEP participants were younger, female, in phase I trials, lived farther away, had lower incomes, and had metastatic disease. Of 87 participants who completed the financial barriers survey, 49 CCEP and 38 matched, non-CCEP participants responded (63% response rate). CCEP participants were more likely to report concerns regarding finances (56% vs. 11%), medical costs (47% vs. 14%), travel (69% vs. 11%), lodging (60% vs. 9%), and insurance coverage (43% vs. 14%) related to trial participation (all p<.01). Conclusion. CT participation increased following implementation of the CCEP and the program enrolled patients experiencing greater financial burden. These findings highlight the need to address the financial burden associated with CT participation. C1 [Nipp, Ryan D.; Lee, Hang; Powell, Elizabeth; Birrer, Nicole E.; Poles, Emily; Finkelstein, Daniel; Winkfield, Karen; Percac-Lima, Sanja; Chabner, Bruce; Moy, Beverly] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Nipp, RD (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9A, Boston, MA 02114 USA. EM RNipp@MGH.Harvard.edu FU Lazarex-MGH Cancer Care Equity Program FX This study was supported by the Lazarex-MGH Cancer Care Equity Program. NR 52 TC 2 Z9 2 U1 1 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD APR PY 2016 VL 21 IS 4 BP 467 EP 474 DI 10.1634/theoncologist.2015-0481 PG 8 WC Oncology SC Oncology GA DJ3UA UT WOS:000374131000010 PM 26975867 ER PT J AU Heist, RS Shim, HS Gingipally, S Mino-Kenudson, M Le, L Gainor, JF Zheng, ZL Aryee, M Xia, JF Jia, PL Jin, HL Zhao, ZM Pao, G Engelman, JA Iafrate, AJ AF Heist, Rebecca S. Shim, Hyo Sup Gingipally, Shalini Mino-Kenudson, Mari Le, Long Gainor, Justin F. Zheng, Zongli Aryee, Martin Xia, Junfeng Jia, Peilin Jin, Hailing Zhao, Zhongming Pao, Gwilliam Engelman, Jeffrey A. Iafrate, A. John TI MET Exon 14 Skipping in Non-Small Cell Lung Cancer SO ONCOLOGIST LA English DT Article DE Lung cancer; MET exon 14 skipping; Targeted therapy ID MUTATIONS; ADENOCARCINOMA; CRIZOTINIB; GEFITINIB; SENSITIVITY; GENE; RESPONSIVENESS; INHIBITION; ACTIVATION; TUMORS AB Background. Non-small cell lung cancers (NSCLCs) harboring specific genetic alterations can be highly sensitive to targeted therapies. Materials and Methods. We performed a targeted rearrangement assay on 54 NSCLCs across all stages that were from patients who were never smokers and did not have driver mutations. Because MET exon 14 skipping was the most frequent alteration found, we surveyed the results for MET exon 14 skipping at Massachusetts General Hospital (MGH) since the inclusion of this alteration into our current molecular profiling panel. Results. In a cohort of 54 never-smokers with lung cancers that were wild-type for known driver mutations, MET exon 14 skipping was the most frequently recurring alteration, occurring in 10 cancers (19%). Clinical testing at MGH via our next-generation sequencing (NGS) and NGS-rearrangement panels showed an additional 16 cases of MET exon 14 skipping, for an overall estimated frequency of 5.6%. A clinical case of a patient with MET exon 14 skipping treated with the MET inhibitor crizotinib is also described. Conclusion. MET exon 14 skipping is a targetable gene alteration found in NSCLC. Patients with these alterations may respond well to MET inhibition. C1 [Heist, Rebecca S.; Gingipally, Shalini; Gainor, Justin F.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Dept Med, Canc Ctr, Boston, MA 02114 USA. [Shim, Hyo Sup; Mino-Kenudson, Mari; Le, Long; Zheng, Zongli; Aryee, Martin; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shim, Hyo Sup] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea. [Xia, Junfeng] Anhui Univ, Inst Hlth Sci, Hefei 230039, Anhui, Peoples R China. [Xia, Junfeng; Jia, Peilin; Zhao, Zhongming] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA. [Jin, Hailing; Pao, Gwilliam] Vanderbilt Univ, Sch Med, Div Hematol Oncol, Dept Med, Nashville, TN 37212 USA. [Zhao, Zhongming] Univ Texas Hlth Sci Ctr Houston, Ctr Precis Hlth, Sch Biomed Informat, Houston, TX 77030 USA. RP Heist, RS (reprint author), Massachusetts Gen Hosp, Dept Med, 32 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM rheist@partners.org RI Zheng, Zongli/B-2917-2011 OI Zheng, Zongli/0000-0003-4849-4903 FU LUNGevity Foundation; Upstage Lung Cancer FX This study was supported by a grant from LUNGevity Foundation and Upstage Lung Cancer. William Pao is currently affiliated with Roche (Basel, Switzerland) as well as Vanderbilt University. NR 27 TC 9 Z9 9 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD APR PY 2016 VL 21 IS 4 BP 481 EP 486 DI 10.1634/theoncologist.2015-0510 PG 6 WC Oncology SC Oncology GA DJ3UA UT WOS:000374131000012 PM 27022036 ER PT J AU Chapuy, CI Sahai, I Sharma, R Zhu, AX Kozyreva, ON AF Chapuy, Claudia I. Sahai, Inderneel Sharma, Rohit Zhu, Andrew X. Kozyreva, Olga N. TI Hyperammonemic Encephalopathy Associated With Fibrolamellar Hepatocellular Carcinoma: Case Report, Literature Review, and Proposed Treatment Algorithm SO ONCOLOGIST LA English DT Article DE Fibrolamellar hepatocellular carcinoma; Hyperammonemia; Paraneoplastic hyperammonemia; OTC deficiency ID CORTICOSTEROIDS; PATIENT AB We report a case of a 31-year-old man with metastatic fibrolamellar hepatocellular carcinoma (FLHCC) treated with gemcitabine and oxaliplatin complicated by hyperammonemic encephalopathy biochemically consistent with acquired ornithine transcarbamylase deficiency. Awareness of FLHCC-associated hyperammonemic encephalopathy and a pathophysiology-based management approach can optimize patient outcome and prevent serious complications. A discussion of the management, literature review, and proposed treatment algorithm of this rare metabolic complication are presented. C1 [Chapuy, Claudia I.; Kozyreva, Olga N.] St Elizabeths Med Ctr, Dana Farber Canc Inst, 736 Cambridge St, Boston, MA 02135 USA. [Sahai, Inderneel; Sharma, Rohit; Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kozyreva, ON (reprint author), St Elizabeths Med Ctr, Dana Farber Canc Inst, 736 Cambridge St, Boston, MA 02135 USA. EM Olga_Kozyreva@dfci.harvard.edu NR 35 TC 1 Z9 1 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD APR PY 2016 VL 21 IS 4 BP 514 EP 520 DI 10.1634/theoncologist.2015-0267 PG 7 WC Oncology SC Oncology GA DJ3UA UT WOS:000374131000018 PM 26975868 ER PT J AU Hogaboom, NS Diehl, JA Oyster, ML Koontz, AM Boninger, ML AF Hogaboom, Nathan S. Diehl, Jessica A. Oyster, Michelle L. Koontz, Alicia M. Boninger, Michael L. TI Ultrasonographic Median Nerve Changes After Repeated Wheelchair Transfers in Persons With Paraplegia: Relationship With Subject Characteristics and Transfer Skills SO PM&R LA English DT Article ID CARPAL-TUNNEL-SYNDROME; SPINAL-CORD-INJURY; UPPER EXTREMITY PAIN; SHOULDER PAIN; USERS; PREVALENCE; SONOGRAPHY; DIAGNOSIS; INDIVIDUALS; POPULATION AB Background: Wheelchair users with spinal cord injuries are susceptible to peripheral neuropathies from overuse, yet no studies have established a relationship between median neuropathy and wheelchair transfers. A more thorough understanding of how transfers and technique contribute to pathologic conditions may guide interventions that curtail its development. Objective: To evaluate the effects of repeated transfers on ultrasound markers for carpal tunnel syndrome (CTS) in people with spinal cord injuries and to relate changes to subject characteristics and transfer skills. Design: Cross-sectional, repeated measures. Setting: Research laboratory and national wheelchair sporting events. Participants: A convenience sample of 30 wheelchair users with nonprogressive paraplegia were recruited via research registries and at the 2013 National Veterans Wheelchair Games and 2014 Paralyzed Veterans of America Buckeye Games. Participants were older than 18 years and could complete transfers independently within 30 seconds without use of their leg muscles. Methods: Demographic questionnaires and physical examinations for CTS were completed. Quantitative ultrasound techniques were used to measure changes in the median nerve after a repeated-transfers protocol. The Transfer Assessment Instrument (TAI) was completed to quantify transfer ability. Main Outcome Measurements: Median nerve cross-sectional area at the level of the pisiform (PCSA) and swelling ratio (SR), transfer quality, and skills via the TAI. Results: PCSA increased after repeated transfers (P < .025). Participants who used safe hand positions had a lower baseline SR (beta = -0.728; P < .01). Participants with a higher body weight had a lower baseline SR provided they performed higher quality transfers. Participants who scooted to the front of the seat prior to transferring (TAI item 7; beta = 0.144; P < .05) and who weighed more (beta = 0.142; P < .05) exhibited greater increases in PCSA in response to transfers. Conclusions: An acute increase was observed in median nerve CSA at the pisiform after repeated wheelchair transfers. Changes were greater in persons with higher body weight and in persons who did not perform certain transfer skills correctly (according to the TAI). It is possible that these factors contribute to chronic injury and possibly CTS. C1 [Hogaboom, Nathan S.; Oyster, Michelle L.; Koontz, Alicia M.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. [Hogaboom, Nathan S.; Oyster, Michelle L.; Koontz, Alicia M.; Boninger, Michael L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Diehl, Jessica A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Boninger, ML (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA.; Boninger, ML (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. EM boninger@pitt.edu OI Hogaboom, Nathan/0000-0002-0601-5751; Boninger, Michael/0000-0001-6966-919X FU National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, U. S. Department of Education [H133N110011]; National Science Foundation Graduate Research Fellowship [1247842] FX This article is the result of work supported with resources and the use of facilities at the Human Engineering Research Laboratories, VA Pittsburgh Healthcare System. This project was supported by the National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, U. S. Department of Education (H133N110011). This article is based on work supported by the National Science Foundation Graduate Research Fellowship (grant #1247842). Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the view of the National Science Foundation. The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. NR 40 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD APR PY 2016 VL 8 IS 4 BP 305 EP 313 DI 10.1016/j.pmrj.2015.08.001 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DJ4LE UT WOS:000374176100002 PM 26265431 ER PT J AU Polak, R Dacey, ML Phillips, EM AF Polak, Rani Dacey, Marie L. Phillips, Edward M. TI Time for Food-Including Nutrition on Physiatrists' Tables SO PM&R LA English DT Article ID LIFE-STYLE MEDICINE; INTERVENTIONS; HEALTH; EDUCATION; BEHAVIOR; IMPACT; ASSOCIATION; PHYSICIANS; PROGRAMS; OUTCOMES AB Unhealthy nutrition is a leading factor in various rehabilitation diagnoses such as stroke and several musculoskeletal complications. Further, the association between nutrition, pain management, and brain plasticity support the importance of having rehabilitation patients follow healthy nutrition guidelines. The goal of this brief report is to emphasize the importance of nutritional counseling to physiatrists and to briefly describe recommended communication skills, behavioral change strategies, and opportunities for interprofessional collaborations. Potential next steps aimed at prescribing nutrition within physiatry clinics are provided. Incorporating healthy nutrition in the physiatrist's personal and professional life presents an opportunity for a meaningful change. Physiatrists can lead the way one bite at a time. The time for a healthy approach to food is now. C1 [Polak, Rani; Phillips, Edward M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Inst Lifestyle Med Phys Med & Rehabil, Suite 344,One Joslin Pl, Boston, MA 02215 USA. [Dacey, Marie L.] MCPHS Univ, Sch Arts & Sci, Dept Behav & Social Sci, Boston, MA USA. RP Polak, R (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Inst Lifestyle Med Phys Med & Rehabil, Suite 344,One Joslin Pl, Boston, MA 02215 USA. EM Rani.polak@joslin.harvard.edu FU Maccabi Healthcare Service; Harvard Medical School-PMR Department; Israeli Cancer Association FX Supported by educational grants from Maccabi Healthcare Service, Harvard Medical School-PM&R Department, and the Israeli Cancer Association. NR 27 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD APR PY 2016 VL 8 IS 4 BP 388 EP 390 DI 10.1016/j.pmrj.2015.09.026 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DJ4LE UT WOS:000374176100020 PM 27068557 ER PT J AU Papageorghiou, AT Thilaganathan, B Bilardo, CM Ngu, A Malinger, G Herrera, M Salomon, LJ Riley, LE Copel, JA AF Papageorghiou, A. T. Thilaganathan, B. Bilardo, C. M. Ngu, A. Malinger, G. Herrera, M. Salomon, L. J. Riley, L. E. Copel, J. A. TI ISUOG Interim Guidance on ultrasound for Zika virus infection in pregnancy: information for healthcare professionals SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Editorial Material ID HEAD CIRCUMFERENCE; GUIDELINES; BRAZIL; BRAIN C1 [Papageorghiou, A. T.; Thilaganathan, B.] St Georges Univ Fdn Hosp NHS Trust, Fetal Med Unit, London, England. [Papageorghiou, A. T.] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England. [Bilardo, C. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Obstet, Groningen, Netherlands. [Ngu, A.] East Melbourne Ultrasound, East Melbourne, Vic, Australia. [Malinger, G.] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Lis Matern Hosp,Div Ultrasound Obstet & Gynecol, IL-69978 Tel Aviv, Israel. [Herrera, M.] Colombian Univ Clin, Colsanitas Clin, Maternal Fetal Med Dept, Bogota, Colombia. [Salomon, L. J.] Univ Paris 05, Necker Enfants Malades Hosp, AP HP, Dept Obstet & Maternal Fetal Med, Paris, France. [Riley, L. E.] Massachusetts Gen Hosp, Obstet & Gynecol, Boston, MA 02114 USA. [Copel, J. A.] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA. RP Papageorghiou, AT (reprint author), St Georges Univ Fdn Hosp NHS Trust, Fetal Med Unit, London, England.; Papageorghiou, AT (reprint author), Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England. NR 17 TC 5 Z9 7 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0960-7692 EI 1469-0705 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD APR PY 2016 VL 47 IS 4 BP 530 EP 532 DI 10.1002/uog.15896 PG 3 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA DJ0SY UT WOS:000373915900027 PM 26969966 ER PT J AU Redondo, MJ Foster, NC Libman, IM Mehta, SN Hathway, JM Bethin, KE Nathan, BM Ecker, MA Shah, AC DuBose, SN Tamborlane, WV Hoffman, RP Wong, JC Maahs, DM Beck, RW DiMeglio, LA AF Redondo, Maria J. Foster, Nicole C. Libman, Ingrid M. Mehta, Sanjeev N. Hathway, Joanne M. Bethin, Kathleen E. Nathan, Brandon M. Ecker, Michelle A. Shah, Avni C. DuBose, Stephanie N. Tamborlane, William V. Hoffman, Robert P. Wong, Jenise C. Maahs, David M. Beck, Roy W. DiMeglio, Linda A. TI Prevalence of cardiovascular risk factors in youth with type 1 diabetes and elevated body mass index SO ACTA DIABETOLOGICA LA English DT Article DE Obesity; Overweight; BMI; Epidemiology; Hypertension; Dyslipidemia; Micro-albuminuria ID EXCHANGE CLINIC REGISTRY; AMERICAN-HEART-ASSOCIATION; PITTSBURGH EPIDEMIOLOGY; CHILDREN; DISEASE; ADOLESCENTS; OBESITY; OVERWEIGHT; ATHEROSCLEROSIS; COMPLICATIONS AB The prevalence of cardiovascular risk factors in children with type 1 diabetes and elevated BMI in the USA is poorly defined. We aimed to test the hypothesis that children with type 1 diabetes who are overweight or obese have increased frequencies of hypertension, dyslipidemia, and micro-/macroalbuminuria compared to their healthy weight peers. We studied 11,348 children 2 to < 18 years of age enrolled in T1D Exchange between September 2010 and August 2012 with type 1 diabetes for a parts per thousand yen1 year and BMI a parts per thousand yen 5th age-/sex-adjusted percentile (mean age 12 years, 49 % female, 78 % non-Hispanic White). Overweight and obesity were defined based on Centers for Disease Control and Prevention criteria. Diagnoses of hypertension, dyslipidemia, and micro-/macroalbuminuria were obtained from medical records. Logistic and linear regression models were used to assess factors associated with weight status. Of the 11,348 participants, 22 % were overweight and 14 % obese. Hypertension and dyslipidemia were diagnosed in 1.0 % and 3.8 % of participants, respectively; micro-/macroalbuminuria was diagnosed in 3.8 % of participants with available data (n = 7,401). The odds of either hypertension or dyslipidemia were higher in obese than healthy weight participants [OR 3.5, 99 % confidence interval (CI) 2.0-6.1 and 2.2, 99 % CI 1.6-3.1, respectively]. Obese participants tended to be diagnosed with micro-/macroalbuminuria less often than healthy weight participants (OR 0.6, 99 % CI 0.4-1.0). Obese children with type 1 diabetes have a higher prevalence of hypertension and dyslipidemia than healthy weight children with type 1 diabetes. The possible association of obesity with lower micro-/macroalbuminuria rates warrants further investigation. C1 [Redondo, Maria J.] Baylor Coll Med, 6621 Fannin St, Houston, TX 77030 USA. [Foster, Nicole C.; DuBose, Stephanie N.; Beck, Roy W.] Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. [Libman, Ingrid M.] UPMC, Childrens Hosp Pittsburgh, 4401 Penn Ave, Pittsburgh, PA 15224 USA. [Mehta, Sanjeev N.; Hathway, Joanne M.] Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. [Bethin, Kathleen E.; Ecker, Michelle A.] SUNY Buffalo, Sch Med & Biomed Sci, 402 Crofts Hall, Buffalo, NY 14260 USA. [Nathan, Brandon M.] Univ Minnesota, 516 Delaware St SE, Minneapolis, MN USA. [Shah, Avni C.] Stanford Univ, Sch Med, 300 Pasteur Dr, Stanford, CA 94305 USA. [Tamborlane, William V.] Yale Univ, 333 Cedar St, New Haven, CT 06520 USA. [Hoffman, Robert P.] Nationwide Childrens Hosp, 700 Childrens Dr, Columbus, OH 43205 USA. [Wong, Jenise C.] Univ Calif San Francisco, 513 Parnassus Ave, San Francisco, CA 94143 USA. [Maahs, David M.] Barbara Davis Ctr Childhood Diabet, 1775 N Ursula St, Aurora, CO 80045 USA. [DiMeglio, Linda A.] Indiana Univ Sch Med, 702 Barnhill Dr, Indianapolis, IN 46202 USA. RP Foster, NC (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM T1DStats@jaeb.org FU Leona M. and Harry B. Helmsley Charitable Trust FX This work was supported through the Leona M. and Harry B. Helmsley Charitable Trust. NR 37 TC 2 Z9 2 U1 1 U2 4 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 0940-5429 EI 1432-5233 J9 ACTA DIABETOL JI Acta Diabetol. PD APR PY 2016 VL 53 IS 2 BP 271 EP 277 DI 10.1007/s00592-015-0785-1 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DJ1GM UT WOS:000373951300012 PM 26077171 ER PT J AU Vodopivec, I Oakley, DH Perugino, CA Venna, N Hedley-Whyte, ET Stone, JH AF Vodopivec, Ivana Oakley, Derek H. Perugino, Cory A. Venna, Nagagopal Hedley-Whyte, E. Tessa Stone, John H. TI A 44-year-old man with eye, kidney, and brain dysfunction SO ANNALS OF NEUROLOGY LA English DT Article ID CEREBRORETINAL VASCULOPATHY; WEGENERS-GRANULOMATOSIS; RETINAL VASCULOPATHY; BEHCETS-DISEASE; HEREDITARY ENDOTHELIOPATHY; NEUROLOGICAL INVOLVEMENT; CEREBRAL LEUKODYSTROPHY; ANTIMALARIAL-DRUGS; EALES-DISEASE; TREX1 AB Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare, autosomal dominant condition caused by mutations of TREX1 (3-prime repair exonuclease-1). The phenotypic expressions range from isolated retinal involvement to varying degrees of retinopathy, cerebral infarction with calcium depositions, nephropathy, and hepatopathy. We report a case of RVCL caused by a novel TREX1 mutation. This patient's multisystem presentation, retinal involvement interpreted as retinal vasculitis, and improvement of neuroimaging abnormalities with dexamethasone led to the accepted diagnosis of a rheumatologic disorder resembling Behcet disease. Clinicians should consider RVCL in any patient with retinal capillary obliterations associated with tumefactive brain lesions or nephropathy. Ann Neurol 2016;79:507-519 C1 [Vodopivec, Ivana; Venna, Nagagopal] Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. [Vodopivec, Ivana; Oakley, Derek H.; Perugino, Cory A.; Venna, Nagagopal; Hedley-Whyte, E. Tessa; Stone, John H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Oakley, Derek H.; Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. [Perugino, Cory A.; Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Vodopivec, I (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM ivodopivec@partners.org FU NIAMS NIH HHS [T32 AR007258] NR 46 TC 1 Z9 1 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2016 VL 79 IS 4 BP 507 EP 519 DI 10.1002/ana.24583 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DJ2AM UT WOS:000374006100001 PM 26691497 ER PT J AU See, RB Awosika, OO Cambria, RP Conrad, MF Lancaster, RT Patel, VI Chitilian, HV Kumar, S Simon, MV AF See, Reiner B. Awosika, Oluwole O. Cambria, Richard P. Conrad, Mark F. Lancaster, Robert T. Patel, Virendra I. Chitilian, Hovig V. Kumar, Sandeep Simon, Mirela V. TI Extended Motor Evoked Potentials Monitoring Helps Prevent Delayed Paraplegia After Aortic Surgery SO ANNALS OF NEUROLOGY LA English DT Article ID THORACOABDOMINAL ANEURYSM REPAIR; COLLATERAL NETWORK CONCEPT; CEREBROSPINAL-FLUID DRAINAGE; SPINAL-CORD PERFUSION; NEUROLOGIC DEFICIT; RISK-FACTOR; MANAGEMENT; PROTECTION; PARALYSIS; OPERATION AB ObjectiveMotor evoked potentials (MEPs) monitoring can promptly detect spinal cord ischemia (SCI) from aortic clamping during open thoracoabdominal aneurysm repair (OTAAR) with distal aortic perfusion (DAP) and thus help decrease the risk of immediate postoperative SCI (IP-SCI). However, neither stable MEPs during aortic clamp interval (ACI) nor absence of IP-SCI eliminate the possibility of delayed postoperative SCI (DP-SCI). We hypothesized that extension of MEPs monitoring beyond ACI can also help decrease the risk of DP-SCI. MethodsWe identified 150 consecutive patients at our institution between April 2005 and October 2014 who underwent OTAAR with DAP and MEPs monitoring and had no IP-SCI. Using logistic regression analysis, we studied the independent effect of extended MEPs monitoring on the risk of developing DP-SCI. We used a propensity score analysis to adjust for potential confounders, such as poorly controlled hypertension, previous aneurysm surgery, splenectomy, acute aortic dissection, aneurysm type, older age, and history of diabetes and smoking. ResultsFrom the 150 patients, 129 (86%) remained neurologically intact whereas 21 (14%) developed DP-SCI. Nineteen of these twenty-one patients (90%) had no extended monitoring. Fifty-seven of fifty-nine (97%) patients who benefited from extended monitoring had no DP-SCI (p = 0.003). Extended MEPs monitoring was independently associated with decreased risk of DP-SCI (odds ratio = 0.14; 95% confidence interval: 0.03, 0.65; p = 0.01). InterpretationMEPs detect the lowest systemic blood pressure that ensures appropriate spinal cord perfusion in the postoperative period. Thus, they inform the hemodynamic management of patients post-OTAAR, particularly in the absence of a reliable neurological exam. Ann Neurol 2016;79:636-645 C1 [See, Reiner B.; Awosika, Oluwole O.; Simon, Mirela V.] Massachusetts Gen Hosp, Dept Neurol, WACC 739G,55 Fruit St, Boston, MA 02114 USA. [Awosika, Oluwole O.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Cambria, Richard P.; Conrad, Mark F.; Lancaster, Robert T.; Patel, Virendra I.] Massachusetts Gen Hosp, Dept Vasc Surg, Boston, MA 02114 USA. [Chitilian, Hovig V.] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Kumar, Sandeep] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Simon, MV (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC 739G,55 Fruit St, Boston, MA 02114 USA. EM mvsimon@mgh.harvard.edu NR 46 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2016 VL 79 IS 4 BP 636 EP 645 DI 10.1002/ana.24610 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DJ2AM UT WOS:000374006100012 PM 26841128 ER PT J AU Dondanville, KA Blankenship, AE Molino, A Resick, PA Wachen, JS Mintz, J Yarvis, JS Litz, BT Borah, EV Roache, JD Young-McCaughan, S Hembree, EA Peterson, AL AF Dondanville, Katherine A. Blankenship, Abby E. Molino, Alma Resick, Patricia A. Wachen, Jennifer Schuster Mintz, Jim Yarvis, Jeffrey S. Litz, Brett T. Borah, Elisa V. Roache, John D. Young-McCaughan, Stacey Hembree, Elizabeth A. Peterson, Alan L. CA STRONG STAR Consortium TI Qualitative examination of cognitive change during PTSD treatment for active duty service members SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Cognitive processing therapy; PTSD; Military personnel; Trauma; Cognitions ID POSTTRAUMATIC-STRESS-DISORDER; PROCESSING THERAPY; VICTIMS; SURVIVORS; SYMPTOMS; EXPOSURE AB The current study investigated changes in service members' cognitions over the course of Cognitive Processing Therapy (CPT) for posttraumatic stress disorder (PTSD). Sixty-three active duty service members with PTSD were drawn from 2 randomized controlled trials of CPT-Cognitive Only (CPT-C). Participants wrote an impact statement about the meaning of their index trauma at the beginning and again at the end of therapy. Clauses from each impact statement were qualitatively coded into three categories for analysis: assimilation, accommodation, and overaccommodation. The PTSD Checklist, Posttraumatic Symptom Scale-Interview Version, and the Beck Depression Inventory-II were administered at baseline and posttreatment. Repeated measures analyses documented a significant decrease in the percentage of assimilated or overaccommodated statements and an increase in the percentage of accommodated statements from the beginning to the end of treatment. Changes in accommodated statements over the course of treatment were negatively associated with PTSD and depression symptom severity, while statements indicative of overaccommodation were positively associated with both PTSD and depression symptom severity. Treatment responders had fewer overaccommodated and more accommodated statements. Findings suggest that CPT-C changes cognitions over the course of treatment. Methodological limitations and the lack of association between assimilation and PTSD symptom severity are further discussed. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Dondanville, Katherine A.; Blankenship, Abby E.; Molino, Alma; Mintz, Jim; Borah, Elisa V.; Roache, John D.; Young-McCaughan, Stacey; Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, 7550 IH-10 West,Suite 1325, San Antonio, TX 78229 USA. [Resick, Patricia A.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Wachen, Jennifer Schuster] Natl Ctr PTSD, White River Jct, VT USA. [Wachen, Jennifer Schuster; Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA. [Wachen, Jennifer Schuster] Boston Univ, Boston, MA 02215 USA. [Yarvis, Jeffrey S.] Carl R Darnall Army Med Ctr, Ft Hood, TX USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Hembree, Elizabeth A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Peterson, Alan L.] South Texas Vet Hlth Care Syst, San Antonio, TX 78228 USA. RP Dondanville, KA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 7550 IH-10 West,Suite 1325, San Antonio, TX 78229 USA. EM dondanville@uthscsa.edu FU U.S. Department of Defense through the U.S. Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, Psychological Health and Traumatic Brain Injury Research Program [W81XWH-08-02-109, W81XWH-08-02-0114, W81XWH-08-02-0116] FX Funding for this work was made possible by the U.S. Department of Defense through the U.S. Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, Psychological Health and Traumatic Brain Injury Research Program awards W81XWH-08-02-109 (Alan Peterson), W81XWH-08-02-0114 (Brett Litz), and W81XWH-08-02-0116 (Patricia Resick). The views expressed in this presentation are solely those of the authors and do not reflect an endorsement by or the official policy of the U.S. Army, the Department of Defense, the Department of Veterans Affairs, or the U.S. Government. NR 26 TC 1 Z9 1 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD APR PY 2016 VL 79 BP 1 EP 6 DI 10.1016/j.brat.2016.01.003 PG 6 WC Psychology, Clinical SC Psychology GA DJ3BQ UT WOS:000374080200001 PM 26874683 ER PT J AU Meng, CL Liu, WJ Huang, HH Wang, Y Chen, BB Freeman, GJ Schneyer, A Lin, HY Xia, Y AF Meng, Chenling Liu, Wenjing Huang, Huihui Wang, Yang Chen, Binbin Freeman, Gordon J. Schneyer, Alan Lin, Herbert Y. Xia, Yin TI Repulsive Guidance Molecule b (RGMb) Is Dispensable for Normal Gonadal Function in Mice SO BIOLOGY OF REPRODUCTION LA English DT Article DE BMP; Dragon; fertility; oocytes; RGMb; spermatocytes ID MORPHOGENETIC PROTEIN CORECEPTOR; REGULATES HEPCIDIN EXPRESSION; INCREASED OVULATION RATE; GERM-CELLS; RETINOIC ACID; DRAGON; MOUSE; SPERMATOGENESIS; HEMOJUVELIN; NEOGENIN AB Bone morphogenetic protein (BMP) signaling plays an important role in spermatogenesis and follicle development. Our previous studies have shown that repulsive guidance molecule b (RGMb, also known as Dragon) is a coreceptor that enhances BMP2 and BMP4 signaling in several cell types and that RGMb is expressed in spermatocytes and spermatids in the testis and in oocytes of the secondary follicles in the ovary. Here, we demonstrated that specific deletion of Rgmb in germ cells in the testis and ovary did not alter Smad1/5/8 phosphorylation, gonadal structures, and fertility. In addition, ovaries from postnatal global Rgmb knockout mice showed similar structures to the wild-type ovaries. Our results suggest that RGMb is not essential for normal gonadal function. C1 [Meng, Chenling; Liu, Wenjing; Huang, Huihui; Wang, Yang; Chen, Binbin; Xia, Yin] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Key Lab Regenerat Med,Minist Educ, Shatin, Hong Kong, Peoples R China. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Schneyer, Alan] Univ Massachusetts, Pioneer Valley Life Sci Inst, Amherst, MA 01003 USA. [Schneyer, Alan] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. [Lin, Herbert Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Ctr Syst Biol,Dept Med, Boston, MA USA. [Xia, Yin] Chinese Univ Hong Kong, Shenzhen Res Inst, Sch Biomed Sci Core Lab, Shenzhen, Peoples R China. RP Xia, Y (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. EM xia.yin@cuhk.edu.hk FU startup fund offered by The Chinese University of Hong Kong; RGC/GRF grant [CUHK477311] FX This work was supported by the startup fund offered by The Chinese University of Hong Kong and an RGC/GRF grant (CUHK477311). NR 35 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD APR 1 PY 2016 VL 94 IS 4 AR 78 DI 10.1095/biolreprod.115.135921 PG 10 WC Reproductive Biology SC Reproductive Biology GA DJ3MA UT WOS:000374108300007 PM 26911425 ER PT J AU Sebastian, A Jung, P Neuhoff, J Wibral, M Fox, PT Lieb, K Fries, P Eickhoff, SB Tuscher, O Mobascher, A AF Sebastian, Alexandra Jung, Patrick Neuhoff, Jonathan Wibral, Michael Fox, Peter T. Lieb, Klaus Fries, Pascal Eickhoff, Simon B. Tuescher, Oliver Mobascher, Arian TI Dissociable attentional and inhibitory networks of dorsal and ventral areas of the right inferior frontal cortex: a combined task-specific and coordinate-based meta-analytic fMRI study SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Attentional capture; Functional magnetic resonance imaging; Meta-analytic connectivity modeling; Right inferior frontal cortex; Right inferior frontal junction; Stop signal task ID TEMPORO-PARIETAL JUNCTION; RESPONSE-INHIBITION; FUNCTIONAL CONNECTIVITY; COGNITIVE CONTROL; HUMAN BRAIN; MODEL; ACTIVATIONS; RELEVANCE; CONTEXT; CHOICE AB The right inferior frontal cortex (rIFC) is frequently activated during executive control tasks. Whereas the function of the dorsal portion of rIFC, more precisely the inferior frontal junction (rIFJ), is convergingly assigned to the attention system, the functional key role of the ventral portion, i.e., the inferior frontal gyrus (rIFG), is hitherto controversially debated. Here, we used a two-step methodical approach to clarify the differential function of rIFJ and rIFG. First, we used event-related functional magnetic resonance imaging (fMRI) during a modified stop signal task with an attentional capture condition (acSST) to delineate attentional from inhibitory motor processes (step 1). Then, we applied coordinate-based meta-analytic connectivity modeling (MACM) to assess functional connectivity profiles of rIFJ and rIFG across various paradigm classes (step 2). As hypothesized, rIFJ activity was associated with the detection of salient stimuli, and was functionally connected to areas of the ventral and dorsal attention network. RIFG was activated during successful response inhibition even when controlling for attentional capture and revealed the highest functional connectivity with core motor areas. Thereby, rIFJ and rIFG delineated largely independent brain networks for attention and motor control. MACM results attributed a more specific attentional function to rIFJ, suggesting an integrative role between stimulus-driven ventral and goal-directed dorsal attention processes. In contrast, rIFG was disclosed as a region of the motor control but not attention system, being essential for response inhibition. The current study provides decisive evidence regarding a more precise functional characterization of rIFC subregions in attention and inhibition. C1 [Sebastian, Alexandra; Jung, Patrick; Neuhoff, Jonathan; Lieb, Klaus; Tuescher, Oliver; Mobascher, Arian] Johannes Gutenberg Univ Mainz, Med Ctr Mainz, Dept Psychiat & Psychotherapy, Focus Program Translat Neurosci FTN, Untere Zahlbacher Str 8, D-55131 Mainz, Germany. [Wibral, Michael] Goethe Univ Frankfurt, Brain Imaging Ctr, MEG Unit, D-60054 Frankfurt, Germany. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Fries, Pascal] Max Planck Gesell, Ernst Strungmann Inst ESI Neurosci Cooperat, Frankfurt, Germany. [Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. [Eickhoff, Simon B.] Forschungszentrum Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany. [Tuescher, Oliver] Univ Freiburg, Med Ctr Freiburg, Dept Neurol, Hugstetter Str 55, D-79106 Freiburg, Germany. [Tuescher, Oliver] Univ Freiburg, Med Ctr Freiburg, Dept Psychiat, Hugstetter Str 55, D-79106 Freiburg, Germany. RP Jung, P (reprint author), Johannes Gutenberg Univ Mainz, Med Ctr Mainz, Dept Psychiat & Psychotherapy, Focus Program Translat Neurosci FTN, Untere Zahlbacher Str 8, D-55131 Mainz, Germany. EM patrjung@uni-mainz.de RI Fries, Pascal/E-3196-2010; OI Fries, Pascal/0000-0002-4270-1468; Wibral, Michael/0000-0001-8010-5862 FU MAIFOR program; Johannes Gutenberg University Medical Center Mainz, Germany; NIH/NIMH [R01 MH074457] FX This work was supported by internal grants of the MAIFOR program and the research focus translational neurosciences (FTN) of the Johannes Gutenberg University Medical Center Mainz, Germany. Comprehensive access to the BrainMap database was authorized by a collaborative-use license agreement, provided to Simon Eickhoff by the University of Texas Health Science Center at San Antonio. BrainMap is supported by NIH/NIMH R01 MH074457. Findings presented in this study are part of the doctoral thesis of Jonathan Neuhoff. NR 51 TC 4 Z9 4 U1 5 U2 12 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD APR PY 2016 VL 221 IS 3 BP 1635 EP 1651 DI 10.1007/s00429-015-0994-y PG 17 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA DI9DK UT WOS:000373801400027 PM 25637472 ER PT J AU Stange, JP Sylvia, LG Magalhaes, PVD Miklowitz, DJ Otto, MW Frank, E Yim, C Berk, M Dougherty, DD Nierenberg, AA Deckersbach, T AF Stange, Jonathan P. Sylvia, Louisa G. da Silva Magalhaes, Pedro Vieira Miklowitz, David J. Otto, Michael W. Frank, Ellen Yim, Christine Berk, Michael Dougherty, Darin D. Nierenberg, Andrew A. Deckersbach, Thilo TI Affective instability and the course of bipolar depression: results from the STEP-BD randomised controlled trial of psychosocial treatment SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; BORDERLINE PERSONALITY-DISORDER; ECOLOGICAL MOMENTARY ASSESSMENT; FAMILY-FOCUSED TREATMENT; SOCIAL RHYTHM THERAPY; COGNITIVE THERAPY; MOOD DISORDERS; RELAPSE PREVENTION; ANXIETY DISORDERS; I DISORDER AB Background Little is known about predictors of recovery from bipolar depression. Aims We investigated affective instability (a pattern of frequent and large mood shifts over time) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychosocial treatment for acute depression. Method A total of 252 out-patients with DSM-IV bipolar I or II disorder and who were depressed enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and were randomised to one of three types of intensive psychotherapy for depression (n = 141) or a brief psychoeducational intervention (n = 111). All analyses were by intention-to-treat. Results Degree of instability of symptoms of depression and mania predicted a lower likelihood of recovery and longer time until recovery, independent of the concurrent effects of symptom severity. Affective instability did not moderate the effects of psychosocial treatment on recovery from depression. Conclusions Affective instability may be a clinically relevant characteristic that influences the course of bipolar depression. Declaration of interest L. S. served as a consultant for Bracket Global and Clintara. M.O. has served as a consultant for MicroTransponder Inc. E.F. has served as a consultant for Servier International. M.B. has received research support from Bristol-Myers Squibb (BMS), Eli Lilly, GlaxoSmithKline (GSK), Organon, Novartis, MaynePharma and Servier, has been a speaker for AstraZeneca, BMS, Eli Lilly, GSK, Janssen Cilag, Lundbeck, Merck, Pfizer, SanofiSynthelabo, Servier, Solvay and Wyeth, and served as a consultant to AstraZeneca, BMS, Eli Lilly, GSK, Janssen Cilag, Lundbeck Merck and Servier. A.A.N. has received honoraria or travel expenses from: American Society of Clinical Psychopharmacology, Australasian Society for Bipolar Disorder, Bayamon Region Psychiatric Society, Belvoir Publishing, Boston Center for the Arts, Corcept, Controlled Risk Insurance Company, Dartmouth, Dey Pharma L.P./Mylan Inc, Israel Society for Biological Psychiatry, Johns Hopkins University, National Association of Continuing Education, PAI, Pamlabs, Physicians Postgraduate Press, Ridge Diagnostics, Slack Publishing, Sunovion, Teva Pharmaceuticals, University of Florida, University of Michigan, University of New Mexico, University of Miami, University of Wisconsin, Wolters Klower Publishing. Potential consulting honoraria from AstraZeneca, BMS, Forest, Pfizer, Ridge Diagnostics. Potential support of research at Massachusetts General Hospital (MGH) through Biogen Idec, Dey Pharmaceuticals, Pamlabs, Shire and Sunovian. He owns stock options in Appliance Computing Inc (MindSite.com) and BrainCells Inc. Additional income is possible from Infomedic.com but no revenue has been received to date. Through MGH, A.A.N. is named for copyrights to: the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery-Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI). T.D. has received honoraria, consultation fees and/or royalties from the MGH Psychiatry Academy, BrainCells Inc, 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 and National Institute on Drug Abuse. He has also participated in research funded by National Institutes of Health, National Institute on Aging, Agency for Healthcare Research and Quality, Janssen Pharmaceuticals, The Forest Research Institute, Shire Development Inc, Medtronic, Cyberonics and Northstar. Copyright and usage (C) The Royal College of Psychiatrists 2015. C1 [Stange, Jonathan P.; Yim, Christine] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Sylvia, Louisa G.; Dougherty, Darin D.; Nierenberg, Andrew A.; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sylvia, Louisa G.; Dougherty, Darin D.; Nierenberg, Andrew A.; Deckersbach, Thilo] Harvard Univ, Sch Med, Boston, MA USA. [da Silva Magalhaes, Pedro Vieira] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Natl Inst Translat Med, BR-90046900 Porto Alegre, RS, Brazil. [Miklowitz, David J.] Univ Calif Los Angeles, Sch Med, Div Child & Adolescent Psychiat, Los Angeles, CA USA. [Otto, Michael W.] Boston Univ, Dept Psychol, 64 Cummington St, Boston, MA 02215 USA. [Frank, Ellen] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Berk, Michael] Deakin Univ, Sch Med, IMPACT Strateg Res Ctr, Geelong, Vic 3217, Australia. [Berk, Michael] Univ Melbourne, Dept Psychiat, Natl Ctr Excellence Youth Mental Hlth, Orygen, Parkville, Vic 3052, Australia. [Berk, Michael] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin & Res Program, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM tdeckersbach@partners.org FU National Institute of Mental Health (NIMH) [N01MH80001]; NIMH [MH29618, MH43931, MH55101, 1K23MH91182-1A1, N01MH80001-01, HR01mh093676, R33MH097007, 1K23MH074895-01A2]; National Alliance for Research on Schizophrenia and Depression; National Research Service from NIMH [F31MH099761]; Brain and Behavior Research Foundation; American Foundation of Suicide Prevention; Danny Alberts Foundation; Deutsch Foundation; Kayne Foundation; Attias Family Foundation; NHMRC [1059660]; NIH [1R34MH091384-01A1]; Cooperative Research Centre; Simons Autism Foundation; Cancer Council of Victoria; Stanley Medical Research Foundation; MBF; NHMRC; Beyond Blue; Rotary Health; Geelong Medical Research Foundation; NARSAD; TSA; OCF; Tufts University FX STEP-BD was funded in part by contract N01MH80001 from the National Institute of Mental Health (NIMH, Gary Sachs). Support for the development of the psychosocial treatments was provided by grants MH29618 (E.F.), MH43931 (D.J.M.) and MH55101 (D.J.M.) from the NIMH and by the National Alliance for Research on Schizophrenia and Depression (D.J.M.). J.S. was supported by National Research Service Award F31MH099761 from NIMH. L.G.S. received research support from NIMH (grant no. 1K23MH91182-1A1 and N01MH80001-01). D.J.M. has received research support from NIMH (grant no. HR01mh093676 and R33MH097007), Brain and Behavior Research Foundation, American Foundation of Suicide Prevention, Danny Alberts Foundation, Deutsch Foundation, Kayne Foundation, and Attias Family Foundation; M.B. is supported by a NHMRC Senior Principal Research Fellowship (1059660) and has received grant/research support from the NIH (grant no. 1R34MH091384-01A1), Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation. T.D. was supported in part by a K-23 NIMH Career Award 1K23MH074895-01A2. His research has also been funded by NARSAD, TSA, OCF and Tufts University. NR 68 TC 1 Z9 1 U1 5 U2 7 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD APR PY 2016 VL 208 IS 4 BP 352 EP 358 DI 10.1192/bjp.bp.114.162073 PG 7 WC Psychiatry SC Psychiatry GA DJ3JG UT WOS:000374100400010 PM 26795426 ER PT J AU Kim, JH Baggish, AL AF Kim, Jonathan H. Baggish, Aaron L. TI Differentiating Exercise-Induced Cardiac Adaptations From Cardiac Pathology: The "Grey Zone" of Clinical Uncertainty SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Review ID LEFT-VENTRICULAR HYPERTROPHY; DISTINGUISHING ATHLETES HEART; STYLE FOOTBALL PARTICIPATION; TASK-FORCE CRITERIA; MAGNETIC-RESONANCE; DIASTOLIC FUNCTION; PROFESSIONAL CYCLISTS; ETHNIC-DIFFERENCES; AEROBIC EXERCISE; UPPER LIMIT AB Exercise-induced cardiac remodelling (EICR) refers to the cardiac structural and functional adaptations that occur in response to the hemodynamic stress of strenuous exercise. Differentiating physiological cardiac hypertrophy as a result of EICR from structural cardiac pathology may be challenging in clinical practice because of the phenotypic crossover between extreme forms of the "hearts of athletes" and mild forms of cardiomyopathy. This structural phenotypic overlap equates to a grey zone of clinical uncertainty. Specifically, asymptomatic athletes presenting with extreme left ventricular (LV) dilatation, LV wall thickening, or right ventricular (RV) dilatation require a systematic and integrative diagnostic approach to achieve accurate clinical differentiation. The combination of a careful clinical history and examination, appropriately used multimodality cardiac imaging, functional exercise testing, ambulatory rhythm monitoring, and occasional detraining typically provides the necessary data for diagnostic purposes and sports participation recommendations. Further clinical distinction of the hearts of athletes from cardiac pathology may emerge from future clinical and translational research efforts establishing exercise-related biomarker profiles and mechanisms underlying EICR adaptations. C1 [Kim, Jonathan H.] Emory Univ, Div Cardiol, Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Performance Program, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, 55 Fruit St,Yawkey Ste 5B, Boston, MA 02114 USA. EM abaggish@partners.org FU NHLBI NIH HHS [R01 HL125869, R01HL117037]; NIDA NIH HHS [R01 DA029141] NR 76 TC 1 Z9 1 U1 4 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X EI 1916-7075 J9 CAN J CARDIOL JI Can. J. Cardiol. PD APR PY 2016 VL 32 IS 4 BP 429 EP 437 DI 10.1016/j.cjca.2015.11.025 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DI5XX UT WOS:000373574900007 PM 26875013 ER PT J AU Planchard, D Brown, KH Kim, DW Kim, SW Ohe, Y Felip, E Leese, P Cantarini, M Vishwanathan, K Janne, PA Ranson, M Dickinson, PA AF Planchard, David Brown, Kathryn H. Kim, Dong-Wan Kim, Sang-We Ohe, Yuichiro Felip, Enriqueta Leese, Philip Cantarini, Mireille Vishwanathan, Karthick Jaenne, Pasi A. Ranson, Malcolm Dickinson, Paul A. TI Osimertinib Western and Asian clinical pharmacokinetics in patients and healthy volunteers: implications for formulation, dose, and dosing frequency in pivotal clinical studies SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Osimertinib; Pharmacokinetics; Bioavailability; Food effect; Multiple dose; Single dose ID CELL LUNG-CANCER; T790M MUTATION; EGFR-TKI; ACQUIRED-RESISTANCE; NSCLC-PATIENTS; GEFITINIB; ADENOCARCINOMA; CHEMOTHERAPY; INHIBITORS; THERAPY AB Osimertinib (AZD9291) 80 mg once daily is approved by the US FDA for the treatment of patients with metastatic EGFR T790M-positive NSCLC whose disease has previously progressed on EGFR-TKI therapy. Osimertinib PK was evaluated to define the dose and dosing interval, whether a fixed-dosing approach can be used globally, and the impact of formulation and food on exposure. AURA (NCT01802632): single- and multiple-dose PK of osimertinib (20-240 mg daily) was determined in patients with advanced NSCLC. Bioavailability study (NCT01951599): single-dose PK of osimertinib (20 mg) was determined in healthy volunteers with administration of capsule, solution, or tablet formulations fasted, and as a tablet in the fed and fasted state. Osimertinib was slowly absorbed and displayed dose-proportional increases in exposure from 20 to 240 mg. Distribution was extensive and clearance low to moderate, resulting in a mean half-life of 48.3 h. Steady state was achieved by 15 days of dosing, consistent with single-dose PK, with a peak-to-trough ratio of 1.6. Two active metabolites circulated at similar to 10 % of osimertinib exposure. Ethnicity did not appear to affect exposure. Osimertinib PK profiles in healthy volunteers were similar to those in patients and were unaffected by formulation. Food caused a clinically insignificant increase in exposure. Osimertinib PK supports once-daily dosing; the same dose for Asian and non-Asian populations; a fixed-dosing approach; a minimal effect of food on exposure; and a switch to tablet formulation without alteration to dose or schedule. Osimertinib plasma concentrations are sustained throughout the dosing period, which is considered optimal for efficacy. C1 [Planchard, David] Inst Gustave Roussy, Dept Med Oncol, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. [Brown, Kathryn H.; Dickinson, Paul A.] AstraZeneca, Quantitat Clin Pharmacol, Macclesfield, Cheshire, England. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Kim, Sang-We] Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Ohe, Yuichiro] Natl Canc Ctr, Div Thorac Oncol, 1-1 Tsukiji 5 chome, Tokyo, Japan. [Felip, Enriqueta] Vall dHebron Univ Hosp, Dept Oncol, Barcelona, Spain. [Leese, Philip] Quintiles, Quintiles Clin Res Unit, Overland Pk, KS USA. [Cantarini, Mireille] AstraZeneca, Res & Dev, Macclesfield, Cheshire, England. [Vishwanathan, Karthick] AstraZeneca, Quantitat Clin Pharmacol, Waltham, MA USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Adult Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Ranson, Malcolm] Univ Manchester, Christie Hosp, Dept Med Oncol, Manchester, Lancs, England. [Dickinson, Paul A.] Seda Pharmaceut Dev Serv, Biohub & Alderley Pk, Alderley Edge SK10 4TG, Cheshire, England. RP Planchard, D (reprint author), Inst Gustave Roussy, Dept Med Oncol, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. EM David.PLANCHARD@gustaveroussy.fr FU AstraZeneca [NCT01802632, NCT01951599] FX These studies (NCT01802632 and NCT01951599) were sponsored by AstraZeneca. NR 18 TC 8 Z9 9 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2016 VL 77 IS 4 BP 767 EP 776 DI 10.1007/s00280-016-2992-z PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA DJ3NF UT WOS:000374111500011 PM 26902828 ER PT J AU John, S Singhal, AB Calabrese, L Uchino, K Hammad, T Tepper, S Stillman, M Mills, B Thankachan, T Hajj-Ali, RA AF John, Seby Singhal, Aneesh B. Calabrese, Leonard Uchino, Ken Hammad, Tariq Tepper, Stewart Stillman, Mark Mills, Brittany Thankachan, Tijy Hajj-Ali, Rula A. TI Long-term outcomes after reversible cerebral vasoconstriction syndrome SO CEPHALALGIA LA English DT Article DE Reversible cerebral vasoconstriction syndrome (RCVS); outcomes; headache; stroke; quality of life ID STROKE AB Background Long-term outcomes of reversible cerebral vasoconstriction syndrome (RCVS) have not been systematically investigated. Methods The following validated questionnaires were mailed to patients recruited from the RCVS registries of two academic hospitals: headache screening form, Headache Impact Test, Migraine Disability Assessment Test, Barthel Index (BI), EuroQoL (EQ-5D-5L) and Patient Health Questionnaire (PHQ-9). Results Of the 191 patients in the registries, 109 could be contacted and 45 responded. Median follow-up time after symptom onset was 78 months. After RCVS resolution, 24 (53%) patients continued to have headache, but the majority (88%) reported improvement in its severity. Thirteen of the 24 patients with persistent headache had a history of migraine prior to RCVS diagnosis. The majority (97.5%) of respondents were functionally independent based on BI scores. EQ-5D-5L showed better scores in the domains of mobility, self-care and usual activities, as compared to pain and anxiety/depression. Patients with persistent headache had significantly higher levels of EQ-5D-5L pain scores. PHQ-9 scores revealed only one patient (3%) with severe depression. Conclusion More than half of RCVS patients will continue to have chronic headaches of mild to moderate intensity that are distinct from the thunderclap headaches at RCVS onset. The vast majority regain complete functional ability. However, pain and anxiety/depression are frequent, often aggravated by concomitant chronic headaches, and may be associated with lower quality of life. C1 [John, Seby; Uchino, Ken] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44195 USA. [Singhal, Aneesh B.; Mills, Brittany; Thankachan, Tijy] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Calabrese, Leonard; Hammad, Tariq; Hajj-Ali, Rula A.] Cleveland Clin, Dept Rheumat & Immunol Dis, Ctr Vasculitis Care & Res, Desk A 50,9500 Euclid Ave, Cleveland, OH 44195 USA. [Tepper, Stewart; Stillman, Mark] Cleveland Clin, Neurol Ctr Pain, Cleveland, OH 44195 USA. RP Hajj-Ali, RA (reprint author), Cleveland Clin, Dept Rheumat & Immunol Dis, Ctr Vasculitis Care & Res, Desk A 50,9500 Euclid Ave, Cleveland, OH 44195 USA. EM hajjalr@ccf.org NR 14 TC 3 Z9 3 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD APR PY 2016 VL 36 IS 4 BP 387 EP 394 DI 10.1177/0333102415591507 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DJ2DS UT WOS:000374014500010 PM 26088331 ER PT J AU Liu, SJ Huang, ZS Wu, QG Huang, ZJ Wu, LR Yan, WL Wang, Q Wang, ZW Chang, DLP Yang, Z AF Liu Si-jun Huang Zhao-sheng Wu Qing-guang Huang Zhang-jie Wu Li-rong Yan Wen-li Wang Qi Wang Zong-wei Chang, David Lungpao Yang Zheng TI Study on diagnosis criteria of fire-heat syndrome based on receiver operating characteristic curve and principal component analysis SO CHINESE JOURNAL OF INTEGRATIVE MEDICINE LA English DT Article DE receiver operating characteristic curve; principal component analysis; diagnostic criteria; fire-heat syndrome; Chinese medicine AB To establish the diagnostic quantitative criteria for fire-heat syndrome (FHS) of Chinese medicine (CM) based on the receiver operating characteristic (ROC) curve and principal component analysis (PCA). The symptoms and signs of FHS cases and healthy subjects from Guangzhou, Henan and Hunan of China were collected through questionnaire, and the diagnostic quantitative score tables were established for the three regions, respectively, with the method of maximum likelihood analysis. The homogeneity test was then performed on the diagnostic score tables for the three regions with ROC curve, and the diagnostic efficiency of diagnostic score tables for the three regions was compared with the prospective test and retrospective test. The method of PCA was adopted to obtain the analysis matrix for classifying the tapes of FHS. Twenty-seven elements of FHS were confirmed through Chi-square test, and the diagnostic score tables for the three regions were established with the method of maximum likelihood analysis on the basis of the collected case data. According to the ROC curve test, the areas under ROC curve of Guangzhou diagnostic score table assessment with candidates in Guangzhou, Henan and Hunan were 0.998, 0.961 and 0.956, respectively. It showed that the diagnostic efficiency of Guangzhou diagnostic score tables was the highest one. With the prospective test, the area under ROC of Guangzhou diagnostic score table was 0.949, and more than any other diagnostic score table. By PCA, FHS was classified into excess fire and deficiency fire, and then classified into syndrome of flaring up of Heart (Xin) fire, syndrome of Lung (Fei)-Stomach (Wei) excess fire, syndrome of deficiency of Liver (Gan)-yin and Kidney (Shen)-yin, and syndrome of deficiency of Lung-yin from the view of viscera. In the retrospective test, the consistency with clinicians' diagnosis was 69.4%, and in the prospective test, it was 70.1%. The Guangzhou diagnostic score table could be used as the recommended criteria for the diagnosis of FHS. The classification of FHS was basically in conformity with the clinical situation. C1 [Liu Si-jun; Wang Qi] Guangzhou Univ Chinese Med, Inst Clin Pharmacol, Guangzhou 510405, Guangdong, Peoples R China. [Huang Zhao-sheng; Wu Qing-guang; Huang Zhang-jie; Wu Li-rong; Yan Wen-li] Guangzhou Univ Chinese Med, Sch Chinese Mat Med, Guangzhou 510405, Guangdong, Peoples R China. [Wang Zong-wei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Chang, David Lungpao; Yang Zheng] Colgate Palmol China Co Ltd, Guangzhou 510730, Guangdong, Peoples R China. RP Huang, ZS (reprint author), Guangzhou Univ Chinese Med, Sch Chinese Mat Med, Guangzhou 510405, Guangdong, Peoples R China. EM vip.hzs@gzhtcm.edu.cn FU Colgate-Palmolive (China) Co., Ltd. FX The authors are grateful to Colgate-Palmolive (China) Co., Ltd. for funding this study. The authors also would like to thank doctors from the First Affiliated Hospital of Guangzhou University of Chinese medicine, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, and the First Hospital of Hunan University of Chinese medicine for collecting clinical data. NR 10 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1672-0415 EI 1993-0402 J9 CHIN J INTEGR MED JI Chin. J. Integr. Med. PD APR PY 2016 VL 22 IS 4 BP 258 EP 266 DI 10.1007/s11655-014-1897-0 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DJ2WI UT WOS:000374065400003 PM 25519441 ER PT J AU Walker, RG Poggioli, T Katsimpardi, L Buchanan, SM Oh, J Wattrus, S Heidecker, B Fong, YW Rubin, LL Ganz, P Thompson, TB Wagers, AJ Lee, RT AF Walker, Ryan G. Poggioli, Tommaso Katsimpardi, Lida Buchanan, Sean M. Oh, Juhyun Wattrus, Sam Heidecker, Bettina Fong, Yick W. Rubin, Lee L. Ganz, Peter Thompson, Thomas B. Wagers, Amy J. Lee, Richard T. TI Biochemistry and Biology of GDF11 and Myostatin Similarities, Differences, and Questions for Future Investigation SO CIRCULATION RESEARCH LA English DT Article DE muscle; heart disease; myocardium; ligands ID GROWTH-FACTOR-BETA; MORPHOGENETIC PROTEIN CORECEPTOR; GROWTH/DIFFERENTIATION FACTOR 11; SKELETAL-MUSCLE REGENERATION; DEVELOPING SPINAL-CORD; HEART-FAILURE; SUPERFAMILY MEMBER; RECEPTOR-BINDING; SATELLITE CELLS; ACTIVIN-A AB Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the transforming growth factor beta superfamily and are often perceived to serve similar or overlapping roles. Yet, despite commonalities in protein sequence, receptor utilization and signaling, accumulating evidence suggests that these 2 ligands can have distinct functions in many situations. GDF11 is essential for mammalian development and has been suggested to regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic processes. In this review, we discuss the biochemical regulation of GDF11 and myostatin and their functions in the heart, skeletal muscle, and brain. We also highlight recent clinical findings with respect to a potential role for GDF11 and/or myostatin in humans with heart disease. Finally, we address key outstanding questions related to GDF11 and myostatin dynamics and signaling during development, growth, and aging. C1 [Walker, Ryan G.; Thompson, Thomas B.] Univ Cincinnati, Coll Med, Dept Mol Genet, Cincinnati, OH 45221 USA. [Poggioli, Tommaso; Katsimpardi, Lida; Buchanan, Sean M.; Oh, Juhyun; Wattrus, Sam; Rubin, Lee L.; Wagers, Amy J.; Lee, Richard T.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Katsimpardi, Lida] Inst Pasteur, Dept Neurosci, Paris, France. [Poggioli, Tommaso] Harvard Univ, Brigham & Womens Hosp, Brigham Regenerat Med Ctr, Cardiovasc Div,Med Sch, Boston, MA 02115 USA. [Fong, Yick W.; Lee, Richard T.] Harvard Univ, Brigham & Womens Hosp, Brigham Regenerat Med Ctr, Dept Med,Med Sch, Boston, MA 02115 USA. [Oh, Juhyun; Wattrus, Sam; Wagers, Amy J.] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Heidecker, Bettina] Univ Herzzentrum, Div Cardiol, Zurich, Switzerland. [Heidecker, Bettina; Ganz, Peter] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Ganz, Peter] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA USA. RP Lee, RT (reprint author), Brigham Regenerat Med Ctr, 65 Landsdowne St, Cambridge, MA 02139 USA.; Wagers, AJ (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, 7 Divin Ave, Cambridge, MA 02138 USA. EM amy_wagers@harvard.edu; RLee@bwh.harvard.edu FU National Institutes of Health; Graduate Dean Fellowship; Glenn Foundation for Medical Research [R01AG032977, R01AG040019, R03AG049657, R56 AG048917, R01 AG033053, RO1GM114640] FX This study was supported, in part, by the National Institutes of Health, the Graduate Dean Fellowship and the Glenn Foundation for Medical Research (R01AG032977, R01AG040019, and R03AG049657 to Dr Lee; R56 AG048917 and R01 AG033053 to Dr Wagers; RO1GM114640 to Dr Thompson; and GD Fellowship to R.G. Walker). NR 169 TC 9 Z9 9 U1 1 U2 16 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 APR 1 PY 2016 VL 118 IS 7 BP 1125 EP 1141 DI 10.1161/CIRCRESAHA.116.308391 PG 17 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA DI9BU UT WOS:000373797200012 PM 27034275 ER PT J AU Chatelle, C De Val, MD Catano, A Chaskis, C Seeldrayers, P Laureys, S Biston, P Schnakers, C AF Chatelle, Camille De Val, Marie-Daniele Catano, Antonio Chaskis, Cristo Seeldrayers, Pierrette Laureys, Steven Biston, Patrick Schnakers, Caroline TI Is the Nociception Coma Scale-Revised a Useful Clinical Tool for Managing Pain in Patients With Disorders of Consciousness? SO CLINICAL JOURNAL OF PAIN LA English DT Article DE minimally conscious state; Nociception Coma Scale-revised; vegetative state/unresponsive wakefulness syndrome; disorders of consciousness; pain management ID UNRESPONSIVE WAKEFULNESS SYNDROME; STATE AB Objectives: Our objective was to assess the clinical usefulness of the Nociception Coma Scale-revised (NCS-R) in pain management of patients with disorders of consciousness. Materials and Methods: Thirty-nine patients with potential painful conditions (eg, due to fractures, decubitus ulcers, or spasticity) were assessed during nursing cares before and after the administration of an analgesic treatment tailored to each patient's clinical status. In addition to the NCS-R, the Glasgow Coma Scale (GCS) was used before and during treatment to observe fluctuations in consciousness. Twenty-three of them had no analgesic treatment before the assessment, whereas the analgesic treatment has been adapted in the other 16 patients. We performed nonparametric Wilcoxon tests to investigate the difference in the NCS-R and GCS total scores but also in the NCS-R subscores before versus during treatment. The effect of the level of consciousness and the etiology were assessed using a Mann-Whitney U test. Results: NCS-R total scores were statistically lower during treatment when compared with the scores obtained before treatment. We also found that the motor, verbal, and facial expression subscores were lower during treatment than before treatment. In contrast, we found no difference between the GCS total scores obtained before versus during treatment. Discussion: Our results suggest that the NCS-R is an interesting clinical tool for pain management. Besides, this tool seems useful when a balance is needed between reduced pain and preserved level of consciousness in patients with disorders of consciousness. C1 [Chatelle, Camille; Laureys, Steven] Univ Liege, Cyclotron Res Ctr, Coma Sci Grp, Liege, Belgium. [De Val, Marie-Daniele] Univ Hosp Charleroi, Acute Pain Serv, Charleroi, Belgium. [De Val, Marie-Daniele; Biston, Patrick] Univ Hosp Charleroi, Dept Intens Care, Charleroi, Belgium. [Catano, Antonio] Univ Hosp Charleroi, Dept Rehabil, Charleroi, Belgium. [Chaskis, Cristo] Univ Hosp Charleroi, Dept Neurosurg, Charleroi, Belgium. [Seeldrayers, Pierrette] Univ Hosp Charleroi, Dept Neurol, Charleroi, Belgium. [Chatelle, Camille] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [Chatelle, Camille] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Schnakers, Caroline] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. RP Schnakers, C (reprint author), Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. EM cschnakers@ucla.edu RI Laureys, Steven/A-3349-2011 FU National Funds for Scientific Research (FNRS); James S. McDonnell Foundation; Mind Science Foundation; University of Liege, Liege; Belgian American Educational Foundation (BAEF); Federation Wallonie Bruxelles International (WBI); Belgian interuniversity attraction pole; Dana Foundation; Massachusetts General Hospital Department of Neurology and Division of Neurocritical Care and Emergency Neurology, Boston FX Supported by the National Funds for Scientific Research (FNRS), James S. McDonnell Foundation, Mind Science Foundation, University of Liege, Liege, the Belgian American Educational Foundation (BAEF), the Federation Wallonie Bruxelles International (WBI), and the Belgian interuniversity attraction pole, the Dana Foundation, and the Massachusetts General Hospital Department of Neurology and Division of Neurocritical Care and Emergency Neurology, Boston. The authors declare no conflict of interest. NR 18 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0749-8047 EI 1536-5409 J9 CLIN J PAIN JI Clin. J. Pain PD APR PY 2016 VL 32 IS 4 BP 321 EP 326 DI 10.1097/AJP.0000000000000259 PG 6 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA DI9MO UT WOS:000373827200007 PM 26035522 ER PT J AU Ko, BJ Park, KH Shin, S Zaichenko, L Davis, CR Crowell, JA Joung, H Mantzoros, CS AF Ko, Byung-Joon Park, Kyung Hee Shin, Sangah Zaichenko, Lesya Davis, Cynthia R. Crowell, Judith A. Joung, Hyojee Mantzoros, Christos S. TI Diet quality and diet patterns in relation to circulating cardiometabolic biomarkers SO CLINICAL NUTRITION LA English DT Article DE Diet quality; Dietary pattern; Leptin Intracellular adhesion molecule-1; C-reactive protein; Irisin ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE; PLASMA-CONCENTRATIONS; ADHESION MOLECULES; CROSSOVER TRIAL; LEPTIN LEVELS; FATTY FISH; INFLAMMATION AB Background & aims: We examined the effects of diet quality and dietary patterns in relation to biomarkers of risk including leptin, soluble intracellular adhesion molecule 1 (sICAM-1), C-reactive protein (CRP), and irisin. Methods: We analyzed data from 196 adults cross-sectionally. Dietary patterns were identified by factor analysis and diet quality scores were generated using a validated food-frequency questionnaire. Results: Both the alternate healthy eating index-2010 (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) scores were negatively related to CRP, even after controlling for body mass index and total energy intake. Similarly, the prudent diet pattern was negatively related to leptin, sICAM-1, and CRP, whereas the Western diet pattern showed positive associations with these markers; however, after adjusting for all confounders, the associations only remained significant for leptin and sICAM-1. Irisin was positively associated with DASH and the prudent diet after controlling for all confounders (standardized beta = 0.23, P = 0.030; standardized beta = 0.25, P = 0.021, respectively). Irisin showed positive associations with increasing fruit consumption, whereas the levels of irisin decreased as meat consumption increased. Conclusions: Irisin was directly associated with healthy diet types and patterns. Further studies regarding these mechanisms are warranted. (C) 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. C1 [Ko, Byung-Joon; Park, Kyung Hee; Zaichenko, Lesya; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA. [Ko, Byung-Joon] Korea Univ, Dept Family Med, Coll Med, Seoul 136705, South Korea. [Ko, Byung-Joon] Sungkyunkwan Univ, Kangbuk Samsung Hosp, Total Healthcare Ctr, Sch Med, Seoul 100742, South Korea. [Park, Kyung Hee] Hallym Univ, Sacred Heart Hosp, Dept Family Med, Gyeonggi Do 431070, South Korea. [Shin, Sangah] Univ Tokyo, Grad Sch Med, AXA Dept Hlth & Human Secur, Tokyo 1130033, Japan. [Shin, Sangah; Joung, Hyojee] Seoul Natl Univ, Inst Hlth & Environm, Seoul 151742, South Korea. [Shin, Sangah; Joung, Hyojee] Seoul Natl Univ, Grad Sch Publ Hlth, Seoul 151742, South Korea. [Davis, Cynthia R.; Crowell, Judith A.] Judge Baker Childrens Ctr, Boston, MA 02120 USA. [Crowell, Judith A.] SUNY Stony Brook, Sch Med, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. [Mantzoros, Christos S.] Harvard Univ, Boston VA Healthcare Syst, Endocrinol Sect, Sch Med, Boston, MA 02130 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, JP9B52A, Boston, MA 02130 USA. EM cmantzor@bidmc.harvard.edu OI Zaichenko, Lesya/0000-0001-8489-3886; Park, Kyung Hee/0000-0001-9806-0076 FU National Institute on Aging Grant [R01 AG032030]; VA Clinical Science Award [1101CX000422-01 A1]; National Center for Research Resources [UL1 RR025758] FX This study was supported by the National Institute on Aging Grant R01 AG032030 and VA Clinical Science Award (1101CX000422-01 A1). The project described was supported by Grant UL1 RR025758 to the Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 30 TC 1 Z9 2 U1 3 U2 14 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0261-5614 EI 1532-1983 J9 CLIN NUTR JI Clin. Nutr. PD APR PY 2016 VL 35 IS 2 BP 484 EP 490 DI 10.1016/j.clnu.2015.03.022 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DJ0BA UT WOS:000373865200026 PM 25912185 ER PT J AU Amrein, K Litonjua, AA Moromizato, T Quraishi, SA Gibbons, FK Pieber, TR Camargo, CA Giovannucci, E Christopher, KB AF Amrein, Karin Litonjua, Augusto A. Moromizato, Takuhiro Quraishi, Sadeq A. Gibbons, Fiona K. Pieber, Thomas R. Camargo, Carlos A., Jr. Giovannucci, Edward Christopher, Kenneth B. TI Increases in pre-hospitalization serum 25(OH)D concentrations are associated with improved 30-day mortality after hospital admission: A cohort study SO CLINICAL NUTRITION LA English DT Article DE 25-Hydroxy vitamin D; Mortality; Hospitalization ID VITAMIN-D DEFICIENCY; RANDOMIZED CONTROLLED-TRIAL; D INSUFFICIENCY; CRITICALLY-ILL; CLINICAL-TRIAL; INFECTIONS; ADULTS; WOMEN; SUPPLEMENTATION AB Context: Pre-hospital vitamin D status may be a modifiable risk factor for all-cause mortality among hospitalized patients. Objective: To examine the association between increases in serum 25-hydroxyvitamin D [25(OH)D] levels during the year before hospitalization and risk of 30-day all-cause mortality after hospital admission. Design: Retrospective cohort study. Setting: Two Boston teaching hospitals. Patients or other participants: We studied 4344 adults hospitalized between 1993 and 2011 who had serum 25(OH)D concentrations measured at least twice within 7-365 days before the index hospitalization. Intervention(s): None. Main outcome measure(s): The exposure of interest was change in pre-hospital serum 25(OH)D concentrations. The main outcome was 30-day all-cause mortality. We used mixed-effects logistic regression to describe how 30-day mortality differed with changes in pre-hospital 25(OH)D concentrations. Additionally, the odds of 30-day mortality in patients with pre-hospital 25(OH)D increases of >= 10 ng/mL was compared to that of patients with increases of <10 ng/mL. Results: In a mixed-effect logistic regression model adjusted for age, gender, race, type (medical/surgical), Deyo-Charlson Index, creatinine and hematocrit, 30-day all-cause mortality rate was 8% (95%Cl: 1-15) lower for each 10 ng/mL increase in pre-hospital 25(OH)D (P = 0.025) compared with the 30-day all-cause mortality rate in the entire cohort. In an adjusted logistic regression model, absolute changes of >= 10 ng/mL in patients with initial 25(OH)D concentrations < 20 ng/mL (n = 1944) decreased the odds of 30-day all-cause mortality by 48% (adjusted OR 0.52; 95%CI 0.30-0.93; P = 0.026) compared to patients with changes of <10 ng/mL. Conclusions: In patients with initial 25(OH)D < 20 ng/mL, subsequent improvements in vitamin D status before hospitalization are associated with decreased odds of 30-day all-cause mortality after hospital admission. A causal relation may not be inferred from this observational study. (C) 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. C1 [Amrein, Karin; Pieber, Thomas R.] Med Univ Graz, Div Endocrinol & Metab, Dept Internal Med, Graz, Austria. [Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Pulm & Crit Care Div, 75 Francis St, Boston, MA 02115 USA. [Moromizato, Takuhiro] Okinawa Hokubu Prefectural Hosp, Dept Med, Nago, Okinawa, Japan. [Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Dept Med, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, 75 Francis St,MRB 418, Boston, MA 02115 USA. EM kbchristopher@partners.org NR 33 TC 1 Z9 1 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0261-5614 EI 1532-1983 J9 CLIN NUTR JI Clin. Nutr. PD APR PY 2016 VL 35 IS 2 BP 514 EP 521 DI 10.1016/j.clnu.2015.03.020 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DJ0BA UT WOS:000373865200030 PM 25935851 ER PT J AU Weckbach, LT Grabmaier, U Clauss, S Wakili, R AF Weckbach, Ludwig T. Grabmaier, Ulrich Clauss, Sebastian Wakili, Reza TI MicroRNAs as a diagnostic tool for heart failure and atrial fibrillation SO CURRENT OPINION IN PHARMACOLOGY LA English DT Review ID CIRCULATING MICRORNAS; MYOCARDIAL-INFARCTION; CATHETER ABLATION; BIOMARKERS; EXPRESSION; MARKERS AB MicroRNAs (miRNAs) are small non-coding RNAs, which are directly involved in the regulation of post-transcriptional gene expression. Their biological function represents a repression of protein expression of the targeted messenger-RNA(s). Expression of several miRNAs is somehow tissue-specific or cell-specific and their expression pattern can reflect an underlying pathophysiological condition. Beyond this biological function their role as potential biomarkers has been emerged in the past years. This was based on the fact that miRNAs can be detected in blood samples (serum or plasma) in a surprisingly stable form, by contrast to mRNAs. This fact made miRNAs interesting candidates for biomarkers providing information with respect to a potentially ongoing pathophysiological condition and could thereby have an impact on specific treatment strategies in patients. In this review we try to provide an overview of the potential role of miRNAs as a diagnostic tool in atrial fibrillation and heart failure patients taken different methodological aspects and distinct type of patients into account. C1 [Weckbach, Ludwig T.; Grabmaier, Ulrich; Clauss, Sebastian; Wakili, Reza] Univ Munich, Univ Hosp Munich, Dept Med 1, Campus Grosshadern, Munich, Germany. [Clauss, Sebastian] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Clauss, Sebastian; Wakili, Reza] DZHK German Ctr Cardiovasc Res, Partner Site Munich, Munich, Germany. RP Wakili, R (reprint author), Univ Munich, Univ Hosp Munich, Dept Med 1, Campus Grosshadern, Munich, Germany.; Wakili, R (reprint author), DZHK German Ctr Cardiovasc Res, Partner Site Munich, Munich, Germany. EM reza.wakili@med.uni-muenchen.de FU People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7) under REA grant [PIOF-GA-2012-328352]; German Centre for Cardiovascular Research (DZHK) [81X2600210, 81X2600204]; European Union's Horizon 2020 research and innovation programme [633193] FX S.C. has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement No. PIOF-GA-2012-328352. S.C. and R.W. were supported by the German Centre for Cardiovascular Research (DZHK, 81X2600210, 81X2600204). R.W. received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 633193 [CATCH ME]. NR 29 TC 10 Z9 10 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 EI 1471-4973 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD APR PY 2016 VL 27 BP 24 EP 30 DI 10.1016/j.coph.2016.01.001 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DJ3AX UT WOS:000374078300006 PM 26852213 ER PT J AU Ushiku, T Ishikawa, S Kakiuchi, M Tanaka, A Katoh, H Aburatani, H Lauwers, GY Fukayama, M AF Ushiku, Tetsuo Ishikawa, Shumpei Kakiuchi, Miwako Tanaka, Atsushi Katoh, Hiroto Aburatani, Hiroyuki Lauwers, Gregory Y. Fukayama, Masashi TI RHOA mutation in diffuse-type gastric cancer: a comparative clinicopathology analysis of 87 cases SO GASTRIC CANCER LA English DT Article DE RHOA; Mutation; Gastric cancer; Diffuse type ID CELL-MIGRATION; TRANSENDOTHELIAL MIGRATION; GENE AMPLIFICATION; INTESTINAL-TYPE; POOR-PROGNOSIS; CARCINOMA; GTPASES; EXPRESSION; OVEREXPRESSION; ADENOCARCINOMA AB Recent studies have discovered recurrent RHOA mutations in diffuse-type gastric cancers. These reports show mutant RhoA is an important cancer driver and is a potential therapeutic target. This study aims to investigate the clinicopathological features of diffuse-type gastric cancers with RHOA mutation. We performed a thorough review of 87 diffuse-type gastric cancers, including 22 RHOA-mutated and 65 RHOA wild-type gastric cancers. Most advanced tumors with RHOA mutation appeared as Borrmann type 3 lesions (81 %) developing in the middle (50 %) or distal (32 %) third of the stomach. Histologically, although all of the tumors were predominantly or exclusively composed of poorly cohesive carcinoma, limited tubular differentiation was also observed in 73 % of the RHOA-mutated tumors. Notably, RHOA-mutated tumors more frequently showed a permeative growth pattern at the edge of the mucosal area (59 %) compared with RHOA wild-type tumors (29 %, P = 0.0202). Additionally, the size ratios of the deeply invasive components to the mucosal components were significantly lower in RHOA-mutated tumors [less than 1.45 (median) in 68 % of cases] than in RHOA wild-type tumors (less than 1.45 in 42 % of cases, P = 0.0482). RHOA mutation did not significantly impact survival in this study. These observations suggest that RHOA mutation may be associated with the growth patterns of diffuse-type gastric cancer but have a limited prognostic impact in isolation. Further studies, including analyses of the other alterations involving the RhoA pathways, such as CLDN18-ARHGAP fusion, as well as functional studies of mutant RhoA, are necessary to clarify the significance of alterations in the RhoA-signaling pathway in diffuse-type gastric cancers. C1 [Ushiku, Tetsuo; Tanaka, Atsushi; Fukayama, Masashi] Univ Tokyo, Grad Sch Med, Dept Pathol, Tokyo, Japan. [Ishikawa, Shumpei; Katoh, Hiroto] Tokyo Med & Dent Univ, Med Res Inst, Dept Genom Pathol, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan. [Kakiuchi, Miwako; Aburatani, Hiroyuki] Univ Tokyo, Res Ctr Adv Sci & Technol, Genome Sci Div, Tokyo, Japan. [Kakiuchi, Miwako] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Tokyo, Japan. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ishikawa, S (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Dept Genom Pathol, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan. EM sish.gpat@mri.tmd.ac.jp FU Project for Development of Innovative Research on Cancer Therapeutics (P-Direct); Ministry of Education, Culture, Sports, Science and Technology of Japan [22134003]; Japan Society for the Promotion of Science [26253021] FX This study was supported by the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Grants-in-Aid for Scientific Research in Innovative Areas to the "Systems Cancer Project'' (grant 22134003) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (S. I.), and by Grant-in-Aid for Scientific Research (A) (grant 26253021) from Japan Society for the Promotion of Science (M.F.). NR 28 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1436-3291 EI 1436-3305 J9 GASTRIC CANCER JI Gastric Cancer PD APR PY 2016 VL 19 IS 2 BP 403 EP 411 DI 10.1007/s10120-015-0493-0 PG 9 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA DI8IW UT WOS:000373745700010 PM 25823974 ER PT J AU Camargo, MC Bowlby, R Chu, A Pedamallu, CS Thorsson, V Elmore, S Mungall, AJ Bass, AJ Gulley, ML Rabkin, CS AF Camargo, M. Constanza Bowlby, Reanne Chu, Andy Pedamallu, Chandra Sekhar Thorsson, Vesteinn Elmore, Sandra Mungall, Andrew J. Bass, Adam J. Gulley, Margaret L. Rabkin, Charles S. TI Validation and calibration of next-generation sequencing to identify Epstein-Barr virus-positive gastric cancer in The Cancer Genome Atlas SO GASTRIC CANCER LA English DT Article DE Stomach cancer; Molecular subtypes; EBV; TCGA ID NASOPHARYNGEAL CARCINOMA; MICRORNAS AB The Epstein-Barr virus (EBV)-positive subtype of gastric adenocarcinoma is conventionally identified by in situ hybridization (ISH) for viral nucleic acids, but next-generation sequencing represents a potential alternative. We therefore determined normalized EBV read counts by whole-genome, whole-exome, mRNA and miRNA sequencing for 295 fresh-frozen gastric tumor samples. Formalin-fixed, paraffin-embedded tissue sections were retrieved for ISH confirmation of 13 high-EBV and 11 low-EBV cases. In pairwise comparisons, individual samples were either concordantly high or concordantly low by all genomic methods for which data were available. Empiric cutoffs of sequencing counts identified 26 (9 %) tumors as EBV positive. EBV positivity or negativity by molecular testing was confirmed by EBER-ISH in all but one tumor evaluated by both approaches (kappa = 0.91). EBV-positive gastric tumors can be accurately identified by quantifying viral sequences in genomic data. Simultaneous analyses of human and viral DNA, mRNA and miRNA could streamline tumor profiling for clinical care and research. C1 [Camargo, M. Constanza; Rabkin, Charles S.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bowlby, Reanne; Chu, Andy; Mungall, Andrew J.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada. [Pedamallu, Chandra Sekhar] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA. [Pedamallu, Chandra Sekhar] Harvard Univ, Cambridge, MA 02142 USA. [Thorsson, Vesteinn] Inst Syst Biol, Seattle, WA 98109 USA. [Elmore, Sandra; Gulley, Margaret L.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Elmore, Sandra; Gulley, Margaret L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Pedamallu, Chandra Sekhar; Bass, Adam J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Rabkin, CS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM rabkinc@mail.nih.gov RI Camargo, M. Constanza/R-9891-2016 FU Intramural Research Program; US National Institutes of Health [5U24CA143799, 5U24CA143835, 5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA143858, 5U24CA143866, 5U24CA143867, 5U24CA143882, 5U24CA143883, 5U24CA144025, U54HG003067, U54HG003079, U54HG003273, P30CA16672] FX This work was supported by the Intramural Research Program and the following grants from the US National Institutes of Health: 5U24CA143799, 5U24CA143835, 5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA143858, 5U24CA143866, 5U24CA143867, 5U24CA143882, 5U24CA143883, 5U24CA144025, U54HG003067, U54HG003079, U54HG003273 and P30CA16672. NR 17 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1436-3291 EI 1436-3305 J9 GASTRIC CANCER JI Gastric Cancer PD APR PY 2016 VL 19 IS 2 BP 676 EP 681 DI 10.1007/s10120-015-0508-x PG 6 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA DI8IW UT WOS:000373745700042 PM 26095338 ER PT J AU Hudry, E Martin, C Gandhi, S Gyorgy, B Scheffer, DI Mu, D Merkel, SF Mingozzi, F Fitzpatrick, Z Dimant, H Masek, M Ragan, T Tan, S Brisson, AR Ramirez, SH Hyman, BT Maguire, CA AF Hudry, E. Martin, C. Gandhi, S. Gyorgy, B. Scheffer, D. I. Mu, D. Merkel, S. F. Mingozzi, F. Fitzpatrick, Z. Dimant, H. Masek, M. Ragan, T. Tan, S. Brisson, A. R. Ramirez, S. H. Hyman, B. T. Maguire, C. A. TI Exosome-associated AAV vector as a robust and convenient neuroscience tool SO GENE THERAPY LA English DT Article ID ADENOASSOCIATED VIRUS PRODUCTION; EXTRACELLULAR VESICLES; ADULT MICE; IN-VIVO; NONHUMAN-PRIMATES; GENE-TRANSFER; MOUSE-BRAIN; DELIVERY; NEURONS; DISEASE AB Adeno-associated virus (AAV) vectors are showing promise in gene therapy trials and have proven to be extremely efficient biological tools in basic neuroscience research. One major limitation to their widespread use in the neuroscience laboratory is the cost, labor, skill and time-intense purification process of AAV. We have recently shown that AAV can associate with exosomes (exo-AAV) when the vector is isolated from conditioned media of producer cells, and the exo-AAV is more resistant to neutralizing anti-AAV antibodies compared with standard AAV. Here, we demonstrate that simple pelleting of exo-AAV from media via ultracentrifugation results in high-titer vector preparations capable of efficient transduction of central nervous system (CNS) cells after systemic injection in mice. We observed that exo-AAV is more efficient at gene delivery to the brain at low vector doses relative to conventional AAV, even when derived from a serotype that does not normally efficiently cross the blood-brain barrier. Similar cell types were transduced by exo-AAV and conventionally purified vector. Importantly, no cellular toxicity was noted in exo-AAV-transduced cells. We demonstrated the utility and robustness of exo-AAV-mediated gene delivery by detecting direct GFP fluorescence after systemic injection, allowing three-dimensional reconstruction of transduced Purkinje cells in the cerebellum using ex vivo serial two-photon tomography. The ease of isolation combined with the high efficiency of transgene expression in the CNS, may enable the widespread use of exo-AAV as a neuroscience research tool. Furthermore, the ability of exo-AAV to evade neutralizing antibodies while still transducing CNS after peripheral delivery is clinically relevant. C1 [Hudry, E.; Martin, C.; Gandhi, S.; Hyman, B. T.] Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Alzheimer Res Unit, Charlestown, MA 02129 USA. [Hudry, E.; Martin, C.; Gandhi, S.; Gyorgy, B.; Mu, D.; Fitzpatrick, Z.; Hyman, B. T.; Maguire, C. A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hudry, E.; Martin, C.; Gandhi, S.; Gyorgy, B.; Mu, D.; Fitzpatrick, Z.; Hyman, B. T.; Maguire, C. A.] Harvard Univ, Sch Med, NeuroDiscovery Ctr, Boston, MA USA. [Gyorgy, B.; Scheffer, D. I.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Merkel, S. F.; Ramirez, S. H.] Temple Univ, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19122 USA. [Mingozzi, F.] Genethon, Evry, France. [Dimant, H.; Masek, M.; Ragan, T.] TissueVision Inc, Cambridge, MA USA. [Tan, S.; Brisson, A. R.] Univ Bordeaux, CNRS, UMR CBMN, Pessac, France. RP Maguire, CA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Bldg 149,13th St, Charlestown, MA 02129 USA. EM cmaguire@mgh.harvard.edu FU NIH/NINDS [R21 NS081374-01, R01 NS086570-01]; American Brain Tumor Association Discovery grant; Alzheimer's Drug Discovery Foundation; JPB Foundation FX We thank Dr Miguel Sena-Esteves for providing the AAV plasmids as well as Dr David P. Corey for the expertise and resources of his laboratory on the cochlear transduction analysis. This work was supported by NIH/NINDS R21 NS081374-01 (CM), an American Brain Tumor Association Discovery grant (CM) and the Alzheimer's Drug Discovery Foundation (EH) and JPB Foundation (BTH). In addition, this work was also partially supported by NIH/NINDS R01 NS086570-01 (SHR). We would like to acknowledge the Nucleic Acid Quantitation Core at MGH Neuroscience Center for qPCR analysis. NR 41 TC 4 Z9 4 U1 4 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD APR PY 2016 VL 23 IS 4 BP 380 EP 392 DI 10.1038/gt.2016.11 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA DJ3SE UT WOS:000374125400007 PM 26836117 ER PT J AU Geller, AC Mayer, JE Sober, AJ Miller, DR Argenziano, G Johnson, TM Swetter, SM AF Geller, Alan C. Mayer, Jonathan E. Sober, Arthur J. Miller, Donald R. Argenziano, Giuseppe Johnson, Timothy M. Swetter, Susan M. TI Total Nevi, Atypical Nevi, and Melanoma Thickness An Analysis of 566 Patients at 2 US Centers SO JAMA DERMATOLOGY LA English DT Article ID CUTANEOUS MELANOMA; MELANOCYTIC NEVI; RISK-FACTORS; DYSPLASTIC NEVI; POPULATION; NUMBER; COMMON AB IMPORTANCE Nevi are among the strongest risk factors for melanoma. However, little is known about the association of many total nevi (TN) or atypical nevi (AN) with tumor thickness. OBJECTIVES To examine the association between age and the number of TN and AN and to explore whether there was a relationship between TN or AN and tumor thickness, controlling for multiple variables. DESIGN, SETTING, AND PARTICIPANTS Survey of patients with melanoma at 2 academic sites and an affiliated Veteran Affairs medical center. Participants included 566 patients surveyed within 3 months of diagnosis. Patients were surveyed in the melanoma clinics from May 17, 2006, through March 31, 2009, within 3 months of diagnostic biopsy. The dates of the analysis were April 1, 2015, to August 1, 2015. MAIN OUTCOMES AND MEASURES Counts of TN and AN were performed at the first visit after diagnosis and were categorized as 0 to 20, 20 to 50, or more than 50 for TN and as 0, 1 to 5, or more than 5 for AN. Tumor thickness was categorized as 2.00 mm or less or as 2.01 mm or greater. All analyses were stratified by patient age (< 60 or >= 60 years). Logistic regression was used to test associations, controlling for age, sex, anatomic location of melanoma, institution, histologic subtype, marital status, performance of skin self-examination, number of health care visits in the past year, mode of melanoma discovery, and receipt of skin examination by a physician. RESUTLTS The study population included 566 patients. Their mean (SD) age was 56.7 (15.9) years, and 39.0%(n = 221) were female. Of 566 patients, the number of TN was classified as 0 to 20 (66.4%[n = 376]), 20 to 50 (20.5%[n = 116]), or more than 50 (13.1%[n = 74]). Atypical nevus counts were 0 (73.3%[n = 415]), 1 to 5 (14.5%[n = 82]), or more than 5 (12.2% [n = 69]). For those younger than 60 years, the presence of more than 50 TN was associated with a sharply reduced risk of thick melanoma (odds ratio, 0.32; 95% CI, 0.12-0.81), and the presence of more than 5 AN compared with no AN was associated with thicker melanoma (odds ratio, 2.43; 95% CI, 1.02-5.75). CONCLUSIONS AND RELEVANCE Most patients with melanoma had few nevi and no AN. In younger patients (< 60 years), thick melanomas were commonly found in those with fewer TN but more AN, suggesting that physicians and patients should not rely on the total nevus count as a sole reason to perform skin examinations or to determine a patient's at-risk status. Younger patients should be educated on the increased risk of thicker melanomas that is associated with having more AN. C1 [Geller, Alan C.] Harvard Univ, Dept Social & Behav Sci, TH Chan Sch Publ Hlth, Kresge Bldg Room 718,677 Huntington Ave, Boston, MA 02115 USA. [Mayer, Jonathan E.] Johns Hopkins Univ, Sch Med, Dept Med, Johns Hopkins Bayview Med Ctr, Baltimore, MD 21205 USA. [Sober, Arthur J.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Miller, Donald R.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Argenziano, Giuseppe] Univ Naples 2, Dermatol Unit, Naples, Italy. [Johnson, Timothy M.] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. [Swetter, Susan M.] Vet Affairs Palo Alto Hlth Care Syst, Dermatol Serv, Palo Alto, CA USA. [Swetter, Susan M.] Stanford Univ, Med Ctr, Dept Dermatol, Pigmented Les & Melanoma Program, Stanford, CA 94305 USA. [Swetter, Susan M.] Inst Canc Res, Stanford, CA USA. RP Geller, AC (reprint author), Harvard Univ, Dept Social & Behav Sci, TH Chan Sch Publ Hlth, Kresge Bldg Room 718,677 Huntington Ave, Boston, MA 02115 USA. EM ageller@hsph.harvard.edu OI Mayer, Jonathan/0000-0001-6376-9886 FU Merck and Co, Inc FX This study was supported by Merck and Co, Inc (Mr Geller and Dr Swetter). NR 13 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD APR PY 2016 VL 152 IS 4 BP 413 EP 418 DI 10.1001/jamadermatol.2016.0027 PG 6 WC Dermatology SC Dermatology GA DJ0TF UT WOS:000373916600013 PM 26934430 ER PT J AU Kroshinsky, D Cotliar, J Hughey, LC Shinkai, K Fox, LP AF Kroshinsky, Daniela Cotliar, Jonathan Hughey, Lauren C. Shinkai, Kanade Fox, Lindy P. TI Association of Dermatology Consultation With Accuracy of Cutaneous Disorder Diagnoses in Hospitalized Patients: A Multicenter Analysis SO JAMA DERMATOLOGY LA English DT Letter C1 [Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,200, Boston, MA 02114 USA. [Cotliar, Jonathan] Northwestern Univ, Dept Dermatol, Evanston, IL USA. [Hughey, Lauren C.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL USA. [Shinkai, Kanade; Fox, Lindy P.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,200, Boston, MA 02114 USA. EM dkroshinsky@mgh.harvard.edu NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD APR PY 2016 VL 152 IS 4 BP 477 EP 480 DI 10.1001/jamadermatol.2015.5098 PG 5 WC Dermatology SC Dermatology GA DJ0TF UT WOS:000373916600028 PM 26762199 ER PT J AU Wehner, MR Linos, E Boscardin, WJ Chren, MM AF Wehner, Mackenzie R. Linos, Eleni Boscardin, W. John Chren, Mary-Margaret TI Competing Risk of Death in Kaplan-Meier Curves When Analyzing Subsequent Keratinocyte Cancer Reply SO JAMA DERMATOLOGY LA English DT Letter C1 [Wehner, Mackenzie R.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Linos, Eleni; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St,Rm N412,POB 0808, San Francisco, CA 94143 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Dermatol Serv, San Francisco, CA USA. RP Chren, MM (reprint author), Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St,Rm N412,POB 0808, San Francisco, CA 94143 USA. EM chrenm@derm.ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD APR PY 2016 VL 152 IS 4 BP 494 EP 495 DI 10.1001/jamadermatol.2015.5153 PG 2 WC Dermatology SC Dermatology GA DJ0TF UT WOS:000373916600039 PM 27074364 ER PT J AU DeKosky, ST Growdon, JH AF DeKosky, Steven T. Growdon, John H. TI The Human Alzheimer Disease Project Answering the Call SO JAMA NEUROLOGY LA English DT Editorial Material C1 [DeKosky, Steven T.] Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32611 USA. [Growdon, John H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Growdon, John H.] Harvard Univ, Sch Med, Boston, MA USA. RP DeKosky, ST (reprint author), Univ Florida, Coll Med, Dept Neurol, McKnight Brain Inst, POB 100236, Gainesville, FL 32610 USA. EM DeKosky@UFL.edu FU NIA NIH HHS [P50AG047266, P50AG005134]; NINDS NIH HHS [R21NS090243] NR 5 TC 0 Z9 0 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD APR PY 2016 VL 73 IS 4 BP 373 EP 374 DI 10.1001/jamaneurol.2015.4512 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DI8YV UT WOS:000373789400001 PM 26831746 ER PT J AU Arsava, EM Kim, GM Oliveira, J Gungor, L Noh, HJ Lordelo, MD Avery, R Maier, IL Ay, H AF Arsava, E. Murat Kim, Gyeong-Moon Oliveira-Filho, Jamary Gungor, Levent Noh, Hyun Jin Lordelo, Morgana de Jesus Avery, Ross Maier, Ilko L. Ay, Hakan TI Prediction of Early Recurrence After Acute Ischemic Stroke SO JAMA NEUROLOGY LA English DT Article ID PERTH COMMUNITY STROKE; RISK-FACTORS; DATA-BANK; INFARCTION; SUBTYPES; TRIAL; DEATH AB IMPORTANCE Approximately half of recurrent strokes occur within days and weeks of an ischemic stroke. It is imperative to identify patients at imminent risk of recurrent stroke because recurrent events lead to prolonged hospitalization, worsened functional outcome, and increased mortality. OBJECTIVE To test the validity of a prognostic score that was exclusively developed to predict early risk of stroke recurrence in a multicenter setting. DESIGN, SETTING, AND PARTICIPANTS This hospital-based cohort study examined patients with and without magnetic resonance imaging-confirmed recurrent stroke within 90 days after an ischemic stroke. The study was performed at 3 teaching hospitals in the United States, Brazil, and South Korea and comprised adult patients admitted within 72 hours of symptom onset with amagnetic resonance imaging-confirmed diagnosis of acute ischemic stroke. Recruitment to the US cohort was performed from June 1, 2009, through April 30, 2011. Recruitment to the Korean and Brazilian cohorts was performed from January 1, 2007, through December 31, 2011. Data analysis was performed from June 1, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES The primary outcome was recurrent ischemic stroke as defined by a clinical incident that was clearly attributable to a new area of brain infarction occurring within the 90 days of index infarction. An investigator who was masked to the patient's recurrence status calculated the Recurrence Risk Estimator (RRE) score for each patient based on information available after initial line of testing in the emergency department. We assessed the predictive performance of the RRE by computing the area under the receiver operating characteristic curve. RESULTS The study included 1468 consecutive patients with 59 recurrent ischemic stroke events. The median age of the patients was 69 (interquartile range, 58-79) years, and 633 (43.1%) were female. The cumulative 90-day recurrence rate was 4.2%(95% CI, 3.2%-5.2%). The mean RRE score was 2.2 (95% CI, 1.9-2.5) in patients with recurrence and 1.0 (95% CI, 1.0-1.1) in patients without. The risk of recurrence increased with a higher RRE score (log-rank test, P < .001). The area under the receiver operating characteristic curve for discrimination was 0.76 (95% CI, 0.70-0.82). The RRE identified 710 patients (48.4%) in the study population as high risk (>10%) or low risk (<1%). The sensitivity and specificity were 38% and 93% for identifying low-risk subsets and 41% and 90% for identifying high-risk subsets, respectively. CONCLUSIONS AND RELEVANCE This study confirms the validity of the RRE score in a multicenter cohort of patients with diverse characteristics. Our findings suggest that the RRE could be useful in identifying high-and low-risk patients for targeted stroke prevention. C1 [Arsava, E. Murat] Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey. [Kim, Gyeong-Moon; Noh, Hyun Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul, South Korea. [Oliveira-Filho, Jamary] Univ Fed Bahia, Stroke Serv, Salvador, BA, Brazil. [Gungor, Levent] Dokuz Mayis Univ, Dept Neurol, Fac Med, Samsun, Turkey. [Lordelo, Morgana de Jesus] Univ Fed Bahia, Postgrad Program Hlth Sci, Salvador, BA, Brazil. [Avery, Ross; Ay, Hakan] Harvard Univ, Sch Med, Dept Radiol, AA Martinos Ctr Biomed Imaging,Massachusetts Gen, Boston, MA 02115 USA. [Maier, Ilko L.] Univ Gottingen, Dept Neurol, Gottingen, Germany. [Ay, Hakan] Harvard Univ, Sch Med, Dept Neurol, Stroke Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,Dept Radiol, 149 13th St,Room 2301, Charlestown, MA 02129 USA.; Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,Dept Neurol, 149 13th St,Room 2301, Charlestown, MA 02129 USA.; Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv,Dept Radiol, 149 13th St,Room 2301, Charlestown, MA 02129 USA.; Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv,Dept Neurol, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@mgh.harvard.edu FU National Institutes of Health [R01-NS059710] FX This study was supported by grant R01-NS059710 from the National Institutes of Health (Dr Ay). NR 21 TC 7 Z9 7 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD APR PY 2016 VL 73 IS 4 BP 396 EP 401 DI 10.1001/jamaneurol.2015.4949 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA DI8YV UT WOS:000373789400011 PM 26926383 ER PT J AU Aguirre-Acevedo, DC Lopera, F Henao, E Tirado, V Munoz, C Giraldo, M Bangdiwala, SI Reiman, EM Tariot, PN Langbaum, JB Quiroz, YT Jaimes, F AF Aguirre-Acevedo, Daniel C. Lopera, Francisco Henao, Eliana Tirado, Victoria Munoz, Claudia Giraldo, Margarita Bangdiwala, Shrikant I. Reiman, Eric M. Tariot, Pierre N. Langbaum, Jessica B. Quiroz, Yakeel T. Jaimes, Fabian TI Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease A Retrospective Cohort Study SO JAMA NEUROLOGY LA English DT Article ID CHANGE-POINT MODEL; NEUROPSYCHOLOGICAL BATTERY; RISK-FACTORS; MEMORY TEST; ONSET; AGE; IMPAIRMENT; BIOMARKERS; LIKELIHOOD; DEMENTIA AB IMPORTANCE Data from an autosomal dominant Alzheimer disease (ADAD) kindred were used to track the longitudinal trajectory of cognitive decline associated with preclinical ADAD and explore factors that may modify the rate of cognitive decline. OBJECTIVES To evaluate the onset and rate of cognitive decline during preclinical ADAD and the effect of socioeconomic, vascular, and genetic factors on the cognitive decline. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective cohort study from January 1, 1995, through June 31, 2012, of individuals from Antioquia, Colombia, who tested positive for the ADAD-associated PSEN1 E280A mutation. Data analysis was performed from August 20, 2014, through November 30, 2015. A mixed-effects model was used to estimate annual rates of change in cognitive test scores and to mark the onset of cognitive decline. MAIN OUTCOMES AND MEASURES Memory, language, praxis, and total scores from the Consortium to Establish a Registry for Alzheimer Disease test battery. Chronologic age was used as a time scale in the models. We explore the effects of sex; educational level; socioeconomic status; residence area; occupation type; marital status; history of hypertension, diabetes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE epsilon 4 on the rates of cognitive decline. RESULTS A total of 493 carriers met the inclusion criteria and were analyzed. A total of 256 carriers had 2 or more assessments. At the time of the initial assessment, participants had a mean (SD) age of 33.4 (11.7) years and a mean (SD) educational level of 7.2 (4.2) years. They were predominantly female (270 [54.8%]), married (293 [59.4%]), and of low socioeconomic status (322 [65.3%]). Word list recall scores provided the earliest indicator of preclinical cognitive decline at 32 years of age, 12 and 17 years before the kindred's respective median ages at mild cognitive impairment and dementia onset. After the change point, carriers had a statistically significant cognitive decline with a loss of 0.24 (95% CI, -0.26 to -0.22) points per year for the word list recall test and 2.13 (95% CI, -2.29 to -1.96) points per year for total scores. Carriers with high educational levels had an increase of approximately 36% in the rate of cognitive decline after the change point when compared with those with low educational levels (-2.89 vs -2.13 points per year, respectively). Onset of cognitive decline was delayed by 3 years in individuals with higher educational levels compared with those with lower educational levels. Those with higher educational level, middle/high socioeconomic status, history of diabetes and hypertension, and tobacco and alcohol use had a steeper cognitive decline after onset. CONCLUSIONS AND RELEVANCE Preclinical cognitive decline was evident in PSEN1 E280A mutation carriers 12 years before the onset of clinical impairment. Educational level may be a protective factor against the onset of cognitive impairment. C1 [Aguirre-Acevedo, Daniel C.; Lopera, Francisco; Henao, Eliana; Tirado, Victoria; Munoz, Claudia; Giraldo, Margarita; Quiroz, Yakeel T.] Univ Antioquia, Neurosci Grp Antioquia, Medellin, Colombia. [Aguirre-Acevedo, Daniel C.; Jaimes, Fabian] Univ Antioquia, Acad Grp Clin Epidemiol, Medellin, Colombia. [Bangdiwala, Shrikant I.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Reiman, Eric M.; Tariot, Pierre N.; Langbaum, Jessica B.] Banner Alzheimers Inst, Phoenix, AZ USA. [Quiroz, Yakeel T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Quiroz, Yakeel T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Jaimes, Fabian] Hosp Pablo Tobon Uribe, Res Unit, Medellin, Colombia. RP Aguirre-Acevedo, DC (reprint author), Univ Antioquia, Neurosci Grp Antioquia, Sede Invest Univ, Calle 62 52-59,Lab 412,Torre 1, Medellin, Colombia. EM daniel.aguirre@udea.edu.co RI Jaimes, Fabian/R-4258-2016; OI Jaimes, Fabian/0000-0002-7315-5367; Aguirre-Acevedo, Daniel Camilo/0000-0002-8195-8821 FU Banner Alzheimer Institute; Departamento Administrativo de Ciencia, Tecnologia e Innovacion, Colciencias, Republic of Colombia [528]; Comite para el desarrollo de la investigacion CODI-Mediana cuantia [609]; National Institute on Aging [P30 AG019610, R01 AG031581]; National Institute of Health Office [DP5OD019833] FX This study was supported by the Banner Alzheimer Institute; grant 528 from the Departamento Administrativo de Ciencia, Tecnologia e Innovacion, Colciencias, Republic of Colombia (Dr Aguirre-Acevedo); grant 609 from Comite para el desarrollo de la investigacion CODI-Mediana cuantia; grants P30 AG019610 and R01 AG031581 from the National Institute on Aging (Dr Reiman); and grant DP5OD019833 from the National Institute of Health Office (Dr Quiroz). NR 31 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD APR PY 2016 VL 73 IS 4 BP 431 EP 438 DI 10.1001/jamaneurol.2015.4851 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DI8YV UT WOS:000373789400016 PM 26902171 ER PT J AU Bunyavanich, S Rifas-Shiman, SL Platts-Mills, TA Workman, L Sordillo, JE Camargo, CA Gillman, MW Gold, DR Litonjua, AA AF Bunyavanich, Supinda Rifas-Shiman, Sheryl L. Platts-Mills, Thomas A. Workman, Lisa Sordillo, Joanne E. Camargo, Carlos A., Jr. Gillman, Matthew W. Gold, Diane R. Litonjua, Augusto A. TI Prenatal, perinatal, and childhood vitamin D exposure and their association with childhood allergic rhinitis and allergic sensitization SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allergic rhinitis; vitamin D; atopy; prenatal; perinatal; childhood; sensitization; food; supplement; allergy ID 25-HYDROXYVITAMIN D; ATOPIC-DERMATITIS; PREGNANT-WOMEN; MID-PREGNANCY; DISEASE; ASTHMA; CHILDREN; DIETARY; POPULATION; HEALTH AB Background: The role of early-life vitamin D in childhood allergy is controversial. Objective: We sought to assess vitamin D exposure in early life by multiple modalities and ascertain its association with childhood allergic rhinitis and allergic sensitization. Methods: One thousand two hundred forty-eight mother-child pairs from a US prebirth cohort unselected for any disease were studied. Vitamin D exposure was assessed by measures of maternal intake during the first and second trimesters of pregnancy and serum 25-hydroxyvitamin D (25[OH]D) levels in mothers during pregnancy, cord blood, and children at school age (median age, 7.7 years; interquartile range, 1.0 years). Tests for associations between vitamin D exposure with ever allergic rhinitis, serum total IgE level, and allergen sensitization at school age were conducted. Results: The correlations between maternal intake of vitamin D during pregnancy and serum 25(OH)D levels in pregnant mothers, cord blood, and children at school age were weak to moderate (r = -0.03 to 0.53). Each 100 IU/d of food-based vitamin D intake during the first and second trimesters (equivalent to the amount of vitamin D in an 8-ounce serving of milk) was associated with 21% and 20% reduced odds of ever allergic rhinitis at school age (odds ratios of 0.79 [95% CI, 0.67-0.92] and 0.80 [95% CI, 0.68-0.93]), respectively. There were no associations between maternal supplemental vitamin D intake or serum 25(OH)D levels at any time point with ever allergic rhinitis. There were no associations between any vitamin D exposure and serum total IgE level or allergen sensitization at school age. Conclusions: Inclusion of foods containing vitamin D in maternal diets during pregnancy may have beneficial effects on childhood allergic rhinitis. C1 [Bunyavanich, Supinda] Icahn Sch Med Mt Sinai, Dept Pediat, Div Allergy & Immunol, One Gustave L Levy Pl 1198, New York, NY 10029 USA. [Bunyavanich, Supinda] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, One Gustave L Levy Pl 1198, New York, NY 10029 USA. [Rifas-Shiman, Sheryl L.; Gillman, Matthew W.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Rifas-Shiman, Sheryl L.; Sordillo, Joanne E.; Camargo, Carlos A., Jr.; Gillman, Matthew W.; Gold, Diane R.; Litonjua, Augusto A.] Harvard Univ, Sch Med, Boston, MA USA. [Platts-Mills, Thomas A.; Workman, Lisa] Univ Virginia Hlth Syst, Asthma & Allerg Dis Ctr, Charlottesville, VA USA. [Sordillo, Joanne E.; Camargo, Carlos A., Jr.; Gold, Diane R.; Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Gold, Diane R.; Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Bunyavanich, S (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl 1198, New York, NY 10029 USA. EM supinda@post.harvard.edu FU National Institutes of Health [AI093538, AI118833, HL61907, HL64925, HD34568, AI35786, HL68041, HL007427] FX Supported by the National Institutes of Health (AI093538, AI118833, HL61907, HL64925, HD34568, AI35786, HL68041, and HL007427). NR 43 TC 1 Z9 1 U1 4 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2016 VL 137 IS 4 BP 1063 EP + DI 10.1016/j.jaci.2015.11.031 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA DI2TG UT WOS:000373351200012 PM 26874366 ER PT J AU Picard, M Pur, L Caiado, J Giavina-Bianchi, P Galvao, VR Berlin, ST Campos, SM Matulonis, UA Castells, MC AF Picard, Matthieu Pur, Leyla Caiado, Joana Giavina-Bianchi, Pedro Galvao, Violeta Regnier Berlin, Suzanne T. Campos, Susana M. Matulonis, Ursula A. Castells, Mariana C. TI Risk stratification and skin testing to guide re-exposure in taxane-induced hypersensitivity reactions SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Taxane; paclitaxel; docetaxel; hypersensitivity; skin test; allergy; risk stratification; desensitization; challenge ID RAPID DESENSITIZATION; CONTRAST-MEDIA; DRUG ALLERGY; PACLITAXEL; ANAPHYLAXIS; DOCETAXEL; CANCER; CHEMOTHERAPY; PROTOCOL; SAFETY AB Background: The optimal approach to patients with hypersensitivity reactions (HSRs) to taxanes has not been established. Objective: We sought to assess the safety and efficacy of risk stratification based on the severity of the initial HSR and skin testing for guiding taxane reintroduction in patients with an HSR to these agents. Methods: Data on 164 patients treated for a taxane-related HSR from April 2011 to August 2014 at the Dana-Farber Cancer Institute and Brigham and Women's Hospital were collected retrospectively. Patients were re-exposed to taxanes either through desensitization, challenge, or regular infusion based on the severity of the initial HSR and skin test response. Depending on the initial risk stratification and tolerance to re-exposure, patients were then treated with shorter desensitization protocols, challenge, or both with the aim of resuming regular infusions, except in patients with a severe immediate initial HSR. Results: Of 138 patients desensitized, 29 (21%) had an immediate and 20 (14%) had a delayed HSR with the procedure. Of 49 patients challenged, 2 (4%) had a mild immediate and 1 (2%) had a delayed HSR with the procedure. No patients had a severe immediate HSR with desensitization or challenge. Thirty-six (22%) patients eventually resumed regular infusions. These patients were more likely to have negative skin test responses and to have experienced a delayed or mild immediate initial HSR. Conclusions: Risk stratification based on the severity of the initial HSR and skin testing to guide taxane reintroduction is safe and allows a significant number of patients to resume regular infusions. C1 [Picard, Matthieu; Pur, Leyla; Caiado, Joana; Giavina-Bianchi, Pedro; Galvao, Violeta Regnier; Castells, Mariana C.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, 1 Jimmy Fund Way,Smith Bldg, Boston, MA 02115 USA. [Berlin, Suzanne T.; Campos, Susana M.; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Castells, MC (reprint author), Brigham & Womens Hosp, 1 Jimmy Fund Way,Smith Bldg, Boston, MA 02115 USA. EM mcastells@partners.org RI Pur Ozyigit, Leyla/O-9045-2015 OI Pur Ozyigit, Leyla/0000-0002-7113-9988 FU Ovations for the Cure of Ovarian Cancer FX Supported by Ovations for the Cure of Ovarian Cancer. NR 35 TC 1 Z9 1 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2016 VL 137 IS 4 BP 1154 EP + DI 10.1016/j.jaci.2015.10.039 PG 23 WC Allergy; Immunology SC Allergy; Immunology GA DI2TG UT WOS:000373351200023 PM 26725998 ER PT J AU Isakova, T Cai, X Lee, J Katz, R Cauley, JA Fried, LF Hoofnagle, AN Satterfield, S Harris, TB Shlipak, MG Sarnak, MJ Ix, JH AF Isakova, Tamara Cai, Xuan Lee, Jungwha Katz, Ronit Cauley, Jane A. Fried, Linda F. Hoofnagle, Andrew N. Satterfield, Suzanne Harris, Tamara B. Shlipak, Michael G. Sarnak, Mark J. Ix, Joachim H. CA Hlth ABC Study TI Associations of FGF23 With Change in Bone Mineral Density and Fracture Risk in Older Individuals SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE FIBROBLAST GROWTH FACTOR 23; BONE MINERAL DENSITY; FRACTURE; CHRONIC KIDNEY DISEASE ID FIBROBLAST GROWTH FACTOR-23; CHRONIC KIDNEY-DISEASE; VITAMIN-D METABOLISM; OSTEOPOROTIC FRACTURES; CARDIOVASCULAR HEALTH; DIETARY PHOSPHATE; HIP-FRACTURES; FGF-23; MEN; FIBROBLAST-GROWTH-FACTOR-23 AB Elevated levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) have been linked to greater risk of fractures in some studies, especially among individuals with chronic kidney disease (CKD). We evaluated FGF23 as a risk factor for bone loss and fractures in the Health, Aging, and Body Composition (Health ABC) study, which is a prospective biracial cohort of well-functioning adults aged 70 to 79 years recruited at two clinical centers in the United States. The sample for the bone mineral density (BMD) analyses consisted of 2234 participants who had at least two serial total hip areal BMD measures. The fracture analyses included 2786 participants, 567 of whom sustained a fracture during a median follow up of 4.95 years. Linear mixed-effects models were used for longitudinal measurements of total hip areal BMD and the proportional subdistribution hazard regression model subject to competing risks of death was used for risk of fracture. The median FGF23 was 46.7 (interquartile range [IQR] 36.7 to 60.2) pg/mL. The mean annualized percent change in total hip areal BMD did not vary significantly according to FGF23 quartile in all participants (p for trend=0.70), but the effect was modified by CKD status (adjusted p for interaction <0.001). Among participants with CKD, the unadjusted mean annualized percent change in total hip areal BMD was greater with higher levels of FGF23 (unadjusted p for trend=0.02), but the trend was attenuated with adjustment for estimated glomerular filtration rate and parathyroid hormone (adjusted p for trend=0.30). FGF23 was not significantly associated with fracture risk in crude (hazard ratio [HR] per doubling of FGF23, 0.97; 95% CI, 0.85 to 1.12) or adjusted models (HR per doubling of FGF23, 1.02; 95% CI, 0.86 to 1.22), and these findings were not modified by gender or CKD status. FGF23 levels are not associated with bone loss or fracture risk in older adults with low prevalence of CKD. (c) 2015 American Society for Bone and Mineral Research. C1 [Isakova, Tamara] Northwestern Univ Feinberg, Sch Med, Dept Med, Div Nephrol & Hypertens, Chicago, IL USA. [Isakova, Tamara; Cai, Xuan] Northwestern Univ Feinberg, Sch Med, Inst Publ Hlth & Med, Ctr Translat Metab & Hlth, Chicago, IL USA. [Lee, Jungwha] Northwestern Univ Feinberg, Sch Med, Dept Preventat Med, Div Biostat, Chicago, IL USA. [Katz, Ronit; Hoofnagle, Andrew N.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Fried, Linda F.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, NIH, Rockville, MD USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol Biostat & Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA USA. [Sarnak, Mark J.] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Ix, Joachim H.] Univ Calif San Diego, Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol & Prevent Med, San Diego, CA 92103 USA. RP Isakova, T (reprint author), 633 N St Clair St, Chicago, IL 60611 USA. EM tamara.isakova@northwestern.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU Carl W. Gottschalk Research Scholar Grant from the American Society of Nephrology Foundation for Kidney Research; National Institutes on Aging [R01AG027002]; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR [R01-NR012459]; NIH, National Institute on Aging; [K23DK087858] FX TI was supported by K23DK087858 and by the Carl W. Gottschalk Research Scholar Grant from the American Society of Nephrology Foundation for Kidney Research. MGS, MS, and JHI and the FGF23 measurements were supported by a grant from the National Institutes on Aging (R01AG027002). The Health ABC Study was supported by the National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and NINR grant R01-NR012459. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 45 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2016 VL 31 IS 4 BP 742 EP 748 DI 10.1002/jbmr.2750 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DJ2BH UT WOS:000374008200006 PM 26590361 ER PT J AU Takatani, R Molinaro, A Grigelioniene, G Tafaj, O Watanabe, T Reyes, M Sharma, A Singhal, V Raymond, FL Linglart, A Juppner, H AF Takatani, Rieko Molinaro, Angelo Grigelioniene, Giedre Tafaj, Olta Watanabe, Tomoyuki Reyes, Monica Sharma, Amita Singhal, Vibha Raymond, F. Lucy Linglart, Agnes Jueppner, Harald TI Analysis of Multiple Families With Single Individuals Affected by Pseudohypoparathyroidism Type Ib (PHP1B) Reveals Only One Novel Maternally Inherited GNAS Deletion SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE EPIGENETICS; GNAS; PSEUDOHYPOPARATHYROIDISM; HORMONAL RESISTANCE ID PATERNAL UNIPARENTAL DISOMY; IMPRINTING CONTROL REGION; GS-ALPHA GENE; AUTOSOMAL-DOMINANT; HORMONE RESISTANCE; EPIGENETIC CHANGES; CHROMOSOME 20Q; MOUSE MODEL; EXON A/B; METHYLATION AB Proximal tubular resistance to parathyroid hormone (PTH) resulting in hypocalcemia and hyperphosphatemia are preeminent abnormalities in pseudohypoparathyroidism type Ib (PHP1B), but resistance toward other hormones as well as variable features of Albright's Hereditary Osteodystrophy (AHO) can occur also. Genomic DNA from PHP1B patients shows epigenetic changes at one or multiple differentially methylated regions (DMRs) within GNAS, the gene encoding Gs and splice variants thereof. In the autosomal dominant disease variant, these methylation abnormalities are caused by deletions in STX16 or GNAS on the maternal allele. The molecular defect(s) leading to sporadic PHP1B (sporPHP1B) remains in most cases unknown and we therefore analyzed 60 sporPHP1B patients and available family members by microsatellite markers, single nucleotide polymorphisms (SNPs), multiplex ligation-dependent probe amplification (MLPA), and methylation-specific MLPA (MS-MLPA). All investigated cases revealed broad GNAS methylation changes, but no evidence for inheritance of two paternal chromosome 20q alleles. Some patients with partial epigenetic modifications in DNA from peripheral blood cells showed more complete GNAS methylation changes when testing their immortalized lymphoblastoid cells. Analysis of siblings and children of sporPHP1B patients provided no evidence for an abnormal mineral ion regulation and no changes in GNAS methylation. Only one patient revealed, based on MLPA and microsatellite analyses, evidence for an allelic loss, which resulted in the discovery of two adjacent, maternally inherited deletions (37,597 and 1427 bp, respectively) that remove the area between GNAS antisense exons 3 and 5, including exon NESP. Our findings thus emphasize that the region comprising antisense exons 3 and 4 is required for establishing all maternal GNAS methylation imprints. The genetic defect(s) leading in sporPHP1B to epigenetic GNAS changes and thus PTH-resistance remains unknown, but it seems unlikely that this disease variant is caused by heterozygous inherited or de novo mutations involving GNAS. (c) 2015 American Society for Bone and Mineral Research. C1 [Takatani, Rieko; Molinaro, Angelo; Grigelioniene, Giedre; Tafaj, Olta; Watanabe, Tomoyuki; Reyes, Monica; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Takatani, Rieko; Molinaro, Angelo; Grigelioniene, Giedre; Tafaj, Olta; Watanabe, Tomoyuki; Reyes, Monica; Sharma, Amita; Singhal, Vibha; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sharma, Amita; Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Singhal, Vibha] Massachusetts Gen Hosp, Pediat Endocrinol Unit, Boston, MA 02114 USA. [Raymond, F. Lucy] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge, England. [Linglart, Agnes] Hop Bicetre, AP HP, French Natl Reference Ctr Rare Disorders Mineral, Paediat Endocrinol & Diabetol, Le Kremlin Bicetre, France. [Linglart, Agnes] Univ Paris Sud, Fac Med, F-94275 Le Kremlin Bicetre, France. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hjueppner@partners.org OI Molinaro, Angelo/0000-0002-8539-4429 FU National Institutes of Health [RO1 DK46718]; Sabbatical Leave Programme of the European Society for Paediatric Endocrinology; Swedish Society of Medicine FX This work was supported by the National Institutes of Health (RO1 DK46718 to HJ), and by the Sabbatical Leave Programme of the European Society for Paediatric Endocrinology and a grant from the Swedish Society of Medicine ( both to G.G.). NR 37 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2016 VL 31 IS 4 BP 796 EP 805 DI 10.1002/jbmr.2731 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DJ2BH UT WOS:000374008200012 PM 26479409 ER PT J AU Wang, J Yu, TT Wang, ZG Ohte, S Yao, RE Zheng, ZJ Geng, J Cai, HQ Ge, YH Li, YC Xu, YL Zhang, QH Gusella, JF Fu, QH Pregizer, S Rosen, V Shen, YP AF Wang, Jian Yu, Tingting Wang, Zhigang Ohte, Satoshi Yao, Ru-en Zheng, Zhaojing Geng, Juan Cai, Haiqing Ge, Yihua Li, Yuchan Xu, Yunlan Zhang, Qinghua Gusella, James F. Fu, Qihua Pregizer, Steven Rosen, Vicki Shen, Yiping TI A New Subtype of Multiple Synostoses Syndrome Is Caused by a Mutation in GDF6 That Decreases Its Sensitivity to Noggin and Enhances Its Potency as a BMP Signal SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE GDF6; NOG; MULTIPLE SYNOSTOSES SYNDROME; BMP; TGF- SIGNALING ID BRACHYDACTYLY TYPE-C; JOINT FORMATION; MOUSE LIMB; CHONDROGENESIS; GROWTH; DIFFERENTIATION; SYMPHALANGISM; CARTILAGE; BONE; GENE AB Growth and differentiation factors (GDFs) are secreted signaling molecules within the BMP family that have critical roles in joint morphogenesis during skeletal development in mice and humans. Using genetic data obtained from a six-generation Chinese family, we identified a missense variant in GDF6 (NP_001001557.1; p.Y444N) that fully segregates with a novel autosomal dominant synostoses (SYNS) phenotype, which we designate as SYNS4. Affected individuals display bilateral wrist and ankle deformities at birth and progressive conductive deafness after age 40 years. We find that the Y444N variant affects a highly conserved residue of GDF6 in a region critical for binding of GDF6 to its receptor(s) and to the BMP antagonist NOG, and show that this mutant GDF6 is a more potent stimulator of the canonical BMP signaling pathway compared with wild-type GDF6. Further, we determine that the enhanced BMP activity exhibited by mutant GDF6 is attributable to resistance to NOG-mediated antagonism. Collectively, our findings indicate that increased BMP signaling owing to a GDF6 gain-of-function mutation is responsible for loss of joint formation and profound functional impairment in patients with SYNS4. More broadly, our study highlights the delicate balance of BMP signaling required for proper joint morphogenesis and reinforces the critical role of BMP signaling in skeletal development. (c) 2015 American Society for Bone and Mineral Research. C1 [Wang, Jian; Yu, Tingting; Yao, Ru-en; Zheng, Zhaojing; Geng, Juan; Fu, Qihua; Shen, Yiping] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Dept Lab Med, Shanghai, Peoples R China. [Wang, Zhigang; Cai, Haiqing; Ge, Yihua; Li, Yuchan; Xu, Yunlan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Dept Pediat Orthoped, Shanghai, Peoples R China. [Ohte, Satoshi; Pregizer, Steven; Rosen, Vicki] Harvard Univ, Sch Dent Med, Dev Biol, Boston, MA 02115 USA. [Zhang, Qinghua] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, State Key Lab Med Genom, Shanghai, Peoples R China. [Gusella, James F.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. [Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Gusella, James F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shen, Yiping] Boston Childrens Hosp, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA. [Shen, Yiping] Claritas Genom, Cambridge, MA USA. RP Shen, YP (reprint author), Boston Childrens Hosp, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA.; Rosen, V (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM vicki_rosen@hsdm.harvard.edu; yiping.shen@childrens.harvard.edu FU National Natural Science Foundation of China [81201353, 81371903, 81472051]; National Institute of General Medical Sciences [GM061354]; NIAMS [R01 AR064277-01A1] FX This work was supported in part by the National Natural Science Foundation of China ( grant nos. 81201353, 81371903, and 81472051 to YS and JW), by the National Institute of General Medical Sciences ( GM061354 Developmental Genome Anatomy Project to JG), and by NIAMS ( grant R01 AR064277-01A1 to VR). NR 37 TC 1 Z9 4 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2016 VL 31 IS 4 BP 882 EP 889 DI 10.1002/jbmr.2761 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DJ2BH UT WOS:000374008200020 PM 26643732 ER PT J AU Melzer, AC Feemster, LC Collins, MP Au, DH AF Melzer, Anne C. Feemster, Laura C. Collins, Margaret P. Au, David H. TI Utilization and effectiveness of pharmacotherapy for Tobacco use following admission for exacerbation of COPD SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE Tobacco; smoking; pulmonary disease; chronic obstructive; nicotine replacement therapy ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CLINICAL-TRIAL; SMOKING-CESSATION; MYOCARDIAL-INFARCTION; DOUBLE-BLIND; HOSPITALIZED-PATIENTS; NICOTINE REPLACEMENT; STOP SMOKING; INTERVENTION; VARENICLINE AB BACKGROUNDPatients admitted for chronic obstructive pulmonary disease (COPD) commonly continue to smoke. The utilization and effectiveness of tobacco cessation medications after discharge is largely unknown. We sought to examine whether pharmacologic treatment of tobacco use following admission for COPD was associated with smoking cessation at 6 to 12 months. METHODSMultivariable logistic regression analysis of a cohort of 1334 smokers, discharged from hospital with a COPD exacerbation between 2005 and 2012, identified administratively within the Veterans Affairs Veterans Integrated Service Network-20, adjusted for variables chosen a priori. Our primary exposure was treatment with any 1 or combination of smoking cessation medications within 90 days of discharge determined from pharmacy records, with the outcome of smoking cessation at 6 to 12 months after discharge. MEASUREMENTS AND MAIN RESULTSFour hundred fifty (33.7%) of the patients were dispensed a smoking cessation medication, with 53.4% receiving a nicotine patch alone. Overall, 19.8% of patients reported quitting smoking at 6 to 12 months. Compared to those not receiving medications, the odds of quitting were not greater among patients dispensed any single or combination of smoking cessation medications within 90 days of discharge (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.74-1.04). Among patients treated with medications compared to nicotine patch alone, varenicline (OR: 2.44, 95% CI: 1.48-4.05) was associated with increased odds of cessation, and short-acting nicotine replacement therapy alone (OR: 0.66, 95% CI: 0.51-0.85) was associated with decreased odds of cessation. CONCLUSIONSTreatment was provided to a minority of subjects and was not associated with cessation, with potential differences observed in effectiveness between medications. Systems-based changes may improve delivery of this key intervention. Journal of Hospital Medicine 2016;11:257-263. (c) 2015 Society of Hospital Medicine C1 [Melzer, Anne C.; Feemster, Laura C.; Au, David H.] Univ Washington, Div Pulm & Crit Care, Seattle, WA 98195 USA. [Melzer, Anne C.; Feemster, Laura C.; Collins, Margaret P.; Au, David H.] VA Puget Sound, Ctr Innovat Veteran Centered & Value Driven Care, Seattle, WA USA. RP Melzer, AC (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM acmelzer@uw.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; University of Washington Department of Pulmonary and Critical Care [HL007287-36]; National Institutes of Health, National Heart, Lung, and Blood Institute [HL111116]; Gilead Sciences; VA Health Services Research and Development FX Dr. Melzer conceived of the research question and performed background reading, analyses, primary drafting, and final revision of the manuscript. Drs. Collins and Feemster participated in finalizing the research question, developing the cohort, performing data collection, and revising the manuscript. Dr. Au provided the database for analysis, helped finalize the research question, and assisted in interpretation of the data and revision of the manuscript. Dr. Au has personally reviewed the data, understands the statistical methods employed, and confirms an understanding of this analysis, that the methods are clearly described, and that they are a fair way to report the results. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, who provided access to data, office space, and programming and data management. 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, the United States government, or the National Institutes of Health. Dr. Au is an unpaid research consultant for Analysis Group. None of the other authors have any conflicts of interest to disclose. Dr. Melzer is supported by an institutional F-32 (HL007287-36) through the University of Washington Department of Pulmonary and Critical Care. Dr. Feemster is supported by an National Institutes of Health, National Heart, Lung, and Blood Institute, K23 Mentored Career Development Award (HL111116). Partial support of this project was provided by Gilead Sciences with research funding to the Seattle Institute for Biomedical and Clinical Research. Additional support was received through the VA Health Services Research and Development. A portion of this work was presented in abstract form at the American Thoracic Society International Meeting, May 2015, in Denver, Colorado. NR 47 TC 1 Z9 1 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD APR PY 2016 VL 11 IS 4 BP 257 EP 263 DI 10.1002/jhm.2519 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DJ0TE UT WOS:000373916500003 PM 26663891 ER PT J AU Haggerty, G Zodan, J Mehra, A Zubair, A Ghosh, K Siefert, CJ Sinclair, SJ DeFife, J AF Haggerty, Greg Zodan, Jennifer Mehra, Ashwin Zubair, Ayyan Ghosh, Krishnendu Siefert, Caleb J. Sinclair, Samuel J. DeFife, Jared TI Reliability and Validity of Prototype Diagnosis for Adolescent Psychopathology SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Adolescents; CBCL; prototype diagnosis; psychopathology; YSR ID STRUCTURED CLINICAL INTERVIEW; PERSONALITY-DISORDERS; CLASSIFICATION AB The current study investigated the interrater reliability and validity of prototype ratings of 5 common adolescent psychiatric disorders: attention-deficit/hyperactivity disorder, conduct disorder, major depressive disorder, generalized anxiety disorder, and posttraumatic stress disorder. One hundred fifty-seven adolescent inpatient participants consented to participate in this study. We compared ratings from 2 inpatient clinicians, blinded to each other's ratings and patient measures, after their separate initial diagnostic interview to assess interrater reliability. Prototype ratings completed by clinicians after their initial diagnostic interview with adolescent inpatients and outpatients were compared with patient-reported behavior problems and parents' report of their child's behavioral problems. Prototype ratings demonstrated good interrater reliability. Clinicians' prototype ratings showed predicted relationships with patient-reported behavior problems and parent-reported behavior problems. Prototype matching seems to be a possible alternative for psychiatric diagnosis. Prototype ratings showed good interrater reliability based on clinicians unique experiences with the patient (as opposed to video-/audio-recorded material) with no training. C1 [Haggerty, Greg; Zodan, Jennifer; Mehra, Ashwin; Zubair, Ayyan; Ghosh, Krishnendu] Nassau Univ, Med Ctr, Von Tauber Inst Global Psychiat, E Meadow, NY USA. [Siefert, Caleb J.] Univ Michigan, Dearborn, MI 48128 USA. [Sinclair, Samuel J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [DeFife, Jared] Emory Univ, Atlanta, GA 30322 USA. RP Haggerty, G (reprint author), 320 1st Ave, Massapequa Pk, NY 11762 USA. EM Ghag541@aol.com FU American Psychoanalytic Association; National Institute of Mental Health [1R21MH097781-01A1] FX The preparation of the article was funded in part by a grant awarded to G.H. from the American Psychoanalytic Association and by the National Institute of Mental Health (grant 1R21MH097781-01A1). NR 21 TC 0 Z9 0 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2016 VL 204 IS 4 BP 287 EP 290 DI 10.1097/NMD.0000000000000492 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DJ0WY UT WOS:000373926300007 PM 26894314 ER PT J AU Thordardottir, EB Hansdottir, I Shipherd, JC Valdimarsdottir, UA Resnick, H Elklit, A Gudmundsdottir, R Gudmundsdottir, B AF Thordardottir, Edda Bjork Hansdottir, Ingunn Shipherd, Jillian C. Valdimarsdottir, Unnur Anna Resnick, Heidi Elklit, Ask Gudmundsdottir, Ragnhildur Gudmundsdottir, Berglind TI Risk Factors for Posttraumatic Stress Symptoms Among Avalanche Survivors A 16-Year Follow-Up SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Disaster; avalanche; risk factors; posttraumatic stress disorder; long-term follow-up ID MENTAL-HEALTH; DISORDER; DISASTER; CONSEQUENCES; PREDICTORS; METAANALYSIS; VOLUNTEERS; DISTRESS; SEQUELAE; TRAUMA AB Few natural disaster studies have assessed factors associated with posttraumatic stress disorder (PTSD) beyond a decade after trauma. Using North's disaster model as a framework, the aim of this study was to identify factors associated with clinically significant posttraumatic stress symptoms (CS-PTSDS) in avalanche survivors (n = 399) 16 years after the disaster. Completed self-report questionnaires were received from 286 (72%) survivors. CS-PTSDS were assessed with the Posttraumatic Diagnostic Scale. Predictors of CS-PTSDS in a multivariate analysis were secondary sequelae factors of lack of social support (adjusted relative risk [RR], 2.90; 95% confidence interval [CI], 1.37-6.13) and financial hardship in the aftermath of the trauma (adjusted RR, 2.47; 95% CI, 1.16-5.26). In addition, the community factor of providing assistance in the aftermath of the avalanche (adjusted RR, 1.95; 95% CI, 1.04-3.64) was inversely associated with CS-PTSDS. Screening for these factors may be useful in identifying those most vulnerable to developing chronic PTSD after this unique type of disaster. C1 [Thordardottir, Edda Bjork; Valdimarsdottir, Unnur Anna; Gudmundsdottir, Ragnhildur] Univ Iceland, Ctr Publ Hlth Sci, Fac Med, IS-101 Reykjavik, Iceland. [Thordardottir, Edda Bjork; Hansdottir, Ingunn] Univ Iceland, Fac Psychol, Sch Hlth Sci, IS-101 Reykjavik, Iceland. [Shipherd, Jillian C.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div 116B 3, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Valdimarsdottir, Unnur Anna] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Resnick, Heidi] Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. [Elklit, Ask] Univ Southern Denmark, Dept Psychol, Odense, Denmark. [Elklit, Ask] Univ Ulster, Dept Psychol, Coleraine BT52 1SA, Londonderry, North Ireland. [Gudmundsdottir, Berglind] Landspitali Natl Univ Hosp Iceland, Mental Hlth Serv, Reykjavik, Iceland. [Gudmundsdottir, Berglind] Univ Iceland, Sch Hlth Sci, Fac Med, IS-101 Reykjavik, Iceland. RP Thordardottir, EB (reprint author), Univ Iceland, Ctr Publ Hlth Sci, Stapi Hringbraut, IS-101 Reykjavik, Iceland. EM eddat@hi.is FU University of Iceland Research Fund; Icelandic Research Fund for Graduate Students (Rannis); Landspitali University Hospital Research Fund; Nordic Centre of Excellence for Resilience and Societal Security - Nordic Societal Security Programme FX This study was funded by the University of Iceland Research Fund, the Icelandic Research Fund for Graduate Students (Rannis), the Landspitali University Hospital Research Fund, and the Nordic Centre of Excellence for Resilience and Societal Security, which is funded by the Nordic Societal Security Programme. NR 35 TC 1 Z9 1 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2016 VL 204 IS 4 BP 298 EP 305 DI 10.1097/NMD.0000000000000475 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DJ0WY UT WOS:000373926300009 PM 26828913 ER PT J AU Baker, AW Goetter, EM Bui, E Shah, R Charney, ME Mauro, C Shear, MK Simon, NM AF Baker, Amanda W. Goetter, Elizabeth M. Bui, Eric Shah, Riva Charney, Meredith E. Mauro, Christine Shear, M. Katherine Simon, Naomi M. TI The Influence of Anxiety Sensitivity on a Wish to Die in Complicated Grief SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE A wish to die; anxiety sensitivity; complicated grief ID SUICIDAL IDEATION; COGNITIVE CONCERNS; DISORDERS; ADULTS; BEREAVEMENT; TEMPERAMENT; SYMPTOMS; TRIAL; SCALE AB Individuals with complicated grief are at elevated risk of suicidal thoughts. Anxiety sensitivity has recently emerged as a risk factor of suicide. This study aimed to investigate a possible association between anxiety sensitivity and a wish to die in individuals with complicated grief. Participants were evaluated for participation in a treatment study and completed an ancillary questionnaire-based study. Participants were 51 bereaved adults evaluated (age: mean, 54 [SD, 13.6] years; 78% [n = 40] women). Logistic regression was used to examine the relationship between anxiety sensitivity and a wish to die. Overall, anxiety sensitivity was associated with a wish to die at the level of a medium effect size, although it did not reach statistical significance. The anxiety sensitivity social concerns subscale was significantly associated with a wish to die. These findings add to a growing literature implicating anxiety sensitivity in reporting a wish to die. C1 [Baker, Amanda W.; Goetter, Elizabeth M.; Bui, Eric; Shah, Riva; Charney, Meredith E.; Simon, Naomi M.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mauro, Christine; Shear, M. Katherine] Columbia Univ, Sch Social Work, New York, NY USA. RP Baker, AW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, One Bowdoin Sq,Suite 650, Boston, MA 02114 USA. EM awbaker@mgh.harvard.edu FU National Institute of Mental Health [R01MH085308]; Highland Street Foundation FX The National Institute of Mental Health (R01MH085308) and the Highland Street Foundation provided funding for this project. NR 26 TC 0 Z9 0 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2016 VL 204 IS 4 BP 314 EP 316 DI 10.1097/NMD.0000000000000465 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DJ0WY UT WOS:000373926300011 PM 27015394 ER PT J AU Jackson, EK Boison, D Schwarzschild, MA Kochanek, PM AF Jackson, Edwin K. Boison, Detlev Schwarzschild, Michael A. Kochanek, Patrick M. TI Purines: forgotten mediators in traumatic brain injury SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE adenosine; cyclic-AMP; neuroprotection; seizure; urate; uric acid ID CAMP-ADENOSINE PATHWAY; SMOOTH-MUSCLE-CELLS; 2,3-CYCLIC NUCLEOTIDE 3-PHOSPHODIESTERASE; MYELIN-ASSOCIATED ENZYME; PARKINSONS-DISEASE RISK; RAT-LIVER MITOCHONDRIA; MAJOR RNASE TYPES; URIC-ACID LEVELS; CYCLIC-AMP; EXTRACELLULAR CAMP AB Recently, the topic of traumatic brain injury has gained attention in both the scientific community and lay press. Similarly, there have been exciting developments on multiple fronts in the area of neurochemistry specifically related to purine biology that are relevant to both neuroprotection and neurodegeneration. At the 2105 meeting of the National Neurotrauma Society, a session sponsored by the International Society for Neurochemistry featured three experts in the field of purine biology who discussed new developments that are germane to both the pathomechanisms of secondary injury and development of therapies for traumatic brain injury. This included presentations by Drs. Edwin Jackson on the novel 2,3-cAMP pathway in neuroprotection, Detlev Boison on adenosine in post-traumatic seizures and epilepsy, and Michael Schwarzschild on the potential of urate to treat central nervous system injury. This mini review summarizes the important findings in these three areas and outlines future directions for the development of new purine-related therapies for traumatic brain injury and other forms of central nervous system injury. C1 [Jackson, Edwin K.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Boison, Detlev] Legacy Res Inst, Robert Stone Dow Neurobiol Labs, Portland, OR USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Boston, MA 02114 USA. [Kochanek, Patrick M.] Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Pittsburgh, PA USA. [Kochanek, Patrick M.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, 3434 Fifth Ave, Pittsburgh, PA 15260 USA. RP Kochanek, PM (reprint author), Univ Pittsburgh, Sch Med, Dept Crit Care Med, 3434 Fifth Ave, Pittsburgh, PA 15260 USA.; Kochanek, PM (reprint author), Univ Pittsburgh, Sch Med, Crit Care Med, 3434 Fifth Ave, Pittsburgh, PA 15260 USA.; Kochanek, PM (reprint author), Univ Pittsburgh, Sch Med, Anesthesiol Pediat Bioengn & Clin & Translat Sci, 3434 Fifth Ave, Pittsburgh, PA 15260 USA.; Kochanek, PM (reprint author), Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, 3434 Fifth Ave, Pittsburgh, PA 15260 USA. EM kochanekpm@ccm.upmc.edu OI Boison, Detlev/0000-0002-7740-5781 FU NIH [HL069846, DK068575, DK079307, DK091190, NS084710]; DOD [W81XWH-10-1-0623, W81XWH-14-2-0018, W81XWH1110150]; [NS070003] FX EKJ is supported by NIH grants HL069846, DK068575, DK079307, and DK091190 and EKJ and PMK by NS070003 and DOD grants W81XWH-10-1-0623 and W81XWH-14-2-0018; and MAS by NIH grant NS084710 and DoD grant W81XWH1110150. The authors have no conflict of interest to declare. NR 151 TC 1 Z9 1 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2016 VL 137 IS 2 BP 142 EP 153 DI 10.1111/jnc.13551 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DJ3YF UT WOS:000374141900002 PM 26809224 ER PT J AU Anderson, KC Alsina, M Atanackovic, D Biermann, JS Chandler, JC Costello, C Djulbegovic, B Fung, HC Gasparetto, C Godby, K Hofmeister, C Holmberg, L Holstein, S Huff, CA Kassim, A Krishnan, AY Kumar, SK Liedtke, M Lunning, M Raje, N Reu, FJ Singhal, S Somlo, G Stockerl-Goldstein, K Treon, SP Weber, D Yahalom, J Shead, DA Kumar, R AF Anderson, Kenneth C. Alsina, Melissa Atanackovic, Djordje Biermann, J. Sybil Chandler, Jason C. Costello, Caitlin Djulbegovic, Benjamin Fung, Henry C. Gasparetto, Cristina Godby, Kelly Hofmeister, Craig Holmberg, Leona Holstein, Sarah Huff, Carol Ann Kassim, Adetola Krishnan, Amrita Y. Kumar, Shaji K. Liedtke, Michaela Lunning, Matthew Raje, Noopur Reu, Frederic J. Singhal, Seema Somlo, George Stockerl-Goldstein, Keith Treon, Steven P. Weber, Donna Yahalom, Joachim Shead, Dorothy A. Kumar, Rashmi TI Multiple Myeloma, Version 3.2016 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ORAL PROTEASOME INHIBITOR; PANOBINOSTAT PLUS BORTEZOMIB; INTERNATIONAL STAGING SYSTEM; LOW-DOSE DEXAMETHASONE; INDUCTION THERAPY; WORKING GROUP; PHASE 1/2; LENALIDOMIDE; COMBINATION; CYCLOPHOSPHAMIDE AB These NCCN Guidelines Insights highlight the important updates/changes specific to the 2016 version of the NCCN Clinical Practice Guidelines in Oncology for Multiple Myeloma. These changes include updated recommendations to the overall management of multiple myeloma from diagnosis and staging to new treatment options. C1 [Anderson, Kenneth C.; Treon, Steven P.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Alsina, Melissa; Djulbegovic, Benjamin] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Atanackovic, Djordje] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Biermann, J. Sybil] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Chandler, Jason C.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Costello, Caitlin] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Fung, Henry C.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Gasparetto, Cristina] Duke Canc Inst, Durham, NC USA. [Godby, Kelly] Univ Alabama Birmingham, Comprehens Canc Ctr, Birmingham, AL USA. [Hofmeister, Craig] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Hofmeister, Craig] Solove Res Inst, Columbus, OH USA. [Holmberg, Leona] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Holstein, Sarah] Roswell Pk Canc Inst, Buffalo, NY USA. [Huff, Carol Ann] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Kassim, Adetola] Vanderbilt Ingram Canc Ctr, Franklin, TN USA. [Krishnan, Amrita Y.; Somlo, George] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Kumar, Shaji K.] Mayo Clin Canc Ctr, Rochester, MN USA. [Liedtke, Michaela] Stanford Canc Inst, Stanford, CA USA. [Lunning, Matthew] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Raje, Noopur] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA. [Reu, Frederic J.] Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH USA. [Reu, Frederic J.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA. [Singhal, Seema] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Stockerl-Goldstein, Keith] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Stockerl-Goldstein, Keith] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Weber, Donna] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Shead, Dorothy A.; Kumar, Rashmi] Natl Comprehens Canc Network, New York, NY USA. RP Anderson, KC (reprint author), Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. RI Djulbegovic, Benjamin/I-3661-2012; Hofmeister, Craig/E-3256-2011 OI Djulbegovic, Benjamin/0000-0003-0671-1447; Hofmeister, Craig/0000-0003-4816-1607 FU AstraZeneca; Bayer Healthcare Pharmaceuticals Inc.; Bristol-Myers Squibb; Clovis Oncology; Foundation Medicine; Genentech; Novartis Oncology; Otsuka America Pharmaceutical, Inc.; Seattle Genetics, Inc.; Takeda Oncology; Actelion Pharmaceuticals US, Inc.; Astellas; Medivation, Inc. FX This activity is supported by educational grants from AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Clovis Oncology, Foundation Medicine, Genentech, Novartis Oncology, Otsuka America Pharmaceutical, Inc., Seattle Genetics, Inc., and Takeda Oncology; support provided by Actelion Pharmaceuticals US, Inc.; and by an independent educational grant from Astellas and Medivation, Inc. NR 37 TC 8 Z9 8 U1 0 U2 2 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2016 VL 14 IS 4 BP 389 EP 400 PG 10 WC Oncology SC Oncology GA DJ3CL UT WOS:000374082300004 PM 27059188 ER PT J AU Rocque, GB Taylor, RA Acemgil, A Li, XL Pisu, M Kenzik, K Jackson, BE Halilova, KI Demark-Wahnefried, W Meneses, K Li, YF Martin, MY Chambless, C Lisovicz, N Fouad, M Partridge, EE Kvale, EA AF Rocque, Gabrielle B. Taylor, Richard A. Acemgil, Aras Li, Xuelin Pisu, Maria Kenzik, Kelly Jackson, Bradford E. Halilova, Karina I. Demark-Wahnefried, Wendy Meneses, Karen Li, Yufeng Martin, Michelle Y. Chambless, Carol Lisovicz, Nedra Fouad, Mona Partridge, Edward E. Kvale, Elizabeth A. CA Patient Care Connect Grp TI Guiding Lay Navigation in Geriatric Patients With Cancer Using a Distress Assessment Tool SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PSYCHOLOGIC DISTRESS; OLDER PATIENTS; BREAST-CANCER; THERMOMETER; VALIDATION; CARE; INTERVENTION; WOMEN AB Background: There is growing interest in psychosocial care and evaluating distress in patients with cancer. As of 2015, the Commission on Cancer requires cancer centers to screen patients for distress, but the optimal approach to implementation remains unclear. Methods: We assessed the feasibility and impact of using distress assessments to frame lay navigator interactions with geriatric patients with cancer who were enrolled in navigation between January 1, 2014, and December 31, 2014. Results: Of the 5,121 patients enrolled in our lay patient navigation program, 4,520 (88%) completed at least one assessment using a standardized distress tool (DT). Navigators used the tool to structure both formal and informal distress assessments. Of all patients, 24% reported distress scores of 4 or greater and 5.5% reported distress scores of 8 or greater. The most common sources of distress at initial assessment were pain, balance/mobility difficulties, and fatigue. Minority patients reported similar sources of distress as the overall program population, with increased relative distress related to logistical issues, such as transportation and financial/insurance questions. Patients were more likely to ask for help with questions about insurance/financial needs (79%), transportation (76%), and knowledge deficits about diet/nutrition (76%) and diagnosis (66%) when these items contributed to distress. Conclusions: Lay navigators were able to routinely screen for patient distress at a high degree of penetration using a structured distress assessment. C1 [Rocque, Gabrielle B.; Taylor, Richard A.; Acemgil, Aras; Pisu, Maria; Halilova, Karina I.; Demark-Wahnefried, Wendy; Meneses, Karen; Li, Yufeng; Chambless, Carol; Lisovicz, Nedra; Fouad, Mona; Partridge, Edward E.; Kvale, Elizabeth A.] Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL USA. [Rocque, Gabrielle B.] Univ Alabama Birmingham, Birmingham Sch Med, Div Hematol & Oncol, Birmingham, AL USA. [Acemgil, Aras; Li, Xuelin; Pisu, Maria; Kenzik, Kelly; Jackson, Bradford E.; Li, Yufeng; Martin, Michelle Y.; Lisovicz, Nedra; Fouad, Mona] Univ Alabama Birmingham, Birmingham Sch Med, Div Prevent Med, Birmingham, AL USA. [Taylor, Richard A.; Meneses, Karen] Univ Alabama Birmingham, Birmingham Sch Nursing, Birmingham, AL USA. [Kvale, Elizabeth A.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Rocque, GB (reprint author), Univ Alabama Birmingham, Sch Med, 1824 6th Ave South,WTI 240E, Birmingham, AL 35294 USA. EM grocque@uabmc.edu FU Walter B. Frommeyer, Jr., Fellowship in Investigative Medicine; Department of Health and Human Services, Centers for Medicare & Medicaid Services [1C1CMS331023] FX Dr. Rocque is supported by a Walter B. Frommeyer, Jr., Fellowship in Investigative Medicine. This funding source had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or approval of the manuscript for publication. Dr. Kvale has disclosed that she is the Palliative Care Medical Director for Aspire Healthcare. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.; This publication was made possible by grant no. 1C1CMS331023 from the Department of Health and Human Services, Centers for Medicare & Medicaid Services. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the US Department of Health and Human Services or any of its agencies. NR 37 TC 1 Z9 1 U1 0 U2 2 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2016 VL 14 IS 4 BP 407 EP 414 PG 8 WC Oncology SC Oncology GA DJ3CL UT WOS:000374082300005 PM 27059189 ER PT J AU Muralidhar, V Catalano, PJ Reznor, G Mahal, BA Choueiri, TK Sweeney, CJ Martin, NE Beard, CJ Chen, YW Nezolosky, MD Hoffman, KE Feng, FY Trinh, QD Nguyen, PL AF Muralidhar, Vinayak Catalano, Paul J. Reznor, Gally Mahal, Brandon A. Choueiri, Toni K. Sweeney, Christopher J. Martin, Neil E. Beard, Clair. J. Chen, Yu-Wei Nezolosky, Michelle D. Hoffman, Karen E. Feng, Felix Y. Quoc-Dien Trinh Nguyen, Paul L. TI Variation in National Use of Long-Term ADT by Disease Aggressiveness Among Men With Unfavorable-Risk Prostate Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ANDROGEN DEPRIVATION THERAPY; AFRICAN-AMERICAN MEN; CARDIOVASCULAR-DISEASE; RADIATION-THERAPY; TRIAL; RADIOTHERAPY; SUPPRESSION; MORTALITY; DURATION AB Background: The current NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer recommend long-term androgen deprivation therapy (ADT) for all men with high-risk prostate cancer treated with external-beam radiation therapy (EBRT). We determined whether the use of long-term ADT varied by the recently defined subcategories of high-risk disease (favorable, other, and very high) versus unfavorable intermediate-risk disease. Methods: We identified 5,524 patients with unfavorable-risk prostate cancer diagnosed from 2004 to 2007 and managed with EBRT using the SEER-Medicare linked database. Patients were stratified by risk group: unfavorable intermediate-risk, favorable high-risk (previously defined and validated as clinical stage T1c, Gleason score of 4+4 = 8, and prostate-specific antigen [PSA] level <10 ng/mL, or clinical stage T1c, Gleason score of 6, and PSA level >20 ng/mL), very-high-risk (clinical stage T3b-T4 or primary Gleason pattern 5), or other high risk (ie, neither favorable nor very high). We used multivariable competing risks regression to estimate the rates of long-term years) ADT by group. Results: Men with favorable high-risk prostate cancer were significantly less likely to receive long-term ADT than those with other high-risk disease (15.4% vs 24.6%, adjusted hazard ratio [AHR], 0.68; 95% CI, 0.60-0.76; P<.001), and similarly likely as those with unfavorable intermediate-risk disease (AHR, 1.10; 95% CI, 0.99-1.23; P=.087). Other high-risk disease was less likely to receive long-term ADT than very high-risk cancer (24.6% vs 30.8%; AHR, 0.83; 95% CI, 0.74-0.93; P=.002). Conclusions: Despite current guidelines, patients with EBRT-managed high-risk prostate cancer received significantly different rates of long-course ADT based on subclassification. Our results suggest that oncologists view these patients as a heterogeneous group with favorable high-risk cancer warranting less aggressive therapy than other high-risk or very high-risk disease. C1 [Muralidhar, Vinayak] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. [Catalano, Paul J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. [Reznor, Gally] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Surg & Publ Hlth,Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. [Mahal, Brandon A.; Martin, Neil E.; Beard, Clair. J.; Chen, Yu-Wei; Nezolosky, Michelle D.; Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. [Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Feng, Felix Y.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Quoc-Dien Trinh] Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu FU Varian; Prostate Cancer Foundation; Fitz's Cancer Warriors, David and Cynthia Chapin, Hugh Simons in Honor of Frank and Anne Simons, Scott Forbes and Gina Ventre Fund; Jeffrey Campbell in Honor of Joan Campbell FX Dr. Nguyen is a consultant for Ferring. Dr. Feng receives research support from Varian, and is on the advisory board for Medivation and Astellas. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.; This work is supported by the Prostate Cancer Foundation; Fitz's Cancer Warriors, David and Cynthia Chapin, Hugh Simons in Honor of Frank and Anne Simons, Scott Forbes and Gina Ventre Fund, Jeffrey Campbell in Honor of Joan Campbell, and a grant from an anonymous family foundation. NR 28 TC 0 Z9 0 U1 1 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2016 VL 14 IS 4 BP 421 EP 428 PG 8 WC Oncology SC Oncology GA DJ3CL UT WOS:000374082300006 PM 27059190 ER PT J AU Coit, DG Thompson, JA Algazi, A Andtbacka, R Bichakjian, CK Carson, WE Daniels, GA DiMaio, D Ernstoff, M Fields, RC Fleming, MD Gonzalez, R Guild, V Halpern, AC Hodi, FS Joseph, RW Lange, JR Martini, MC Materin, MA Olszanski, AJ Ross, MI Salama, AK Skitzki, J Sosman, J Swetter, SM Tanabe, KK Torres-Roca, JF Trisal, V Urist, MM McMillian, N Engh, A AF Coit, Daniel G. Thompson, John A. Algazi, Alain Andtbacka, Robert Bichakjian, Christopher K. Carson, William E., III Daniels, Gregory A. DiMaio, Dominick Ernstoff, Marc Fields, Ryan C. Fleming, Martin D. Gonzalez, Rene Guild, Valerie Halpern, Allan C. Hodi, F. Stephen, Jr. Joseph, Richard W. Lange, Julie R. Martini, Mary C. Materin, Miguel A. Olszanski, Anthony J. Ross, Merrick I. Salama, April K. Skitzki, Joseph Sosman, Jeff Swetter, Susan M. Tanabe, Kenneth K. Torres-Roca, Javier F. Trisal, Vijay Urist, Marshall M. McMillian, Nicole Engh, Anita TI Melanoma, Version 2.2016 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID ISOLATED LIMB PERFUSION; CUTANEOUS METASTATIC MELANOMA; CARBON-DIOXIDE LASER; IN-TRANSIT MELANOMA; STAGE-III MELANOMA; COOPERATIVE-ONCOLOGY-GROUP; SENTINEL LYMPH-NODE; HIGH-RISK MELANOMA; HIGH-DOSE INTERFERON-ALPHA-2B; BACILLUS-CALMETTE-GUERIN AB This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Melanoma focuses on adjuvant therapy and treatment of in-transit disease, because substantial changes were made to the recommendations for the 2016 update. Depending on the stage of the disease, options for adjuvant therapy now include biochemotherapy and high dose ipilimumab. Treatment options for in-transit disease now include intralesional injection with talimogene laherparepvec (T-VEC), a new immunotherapy. These additions prompted reassessment of the data supporting older recommended treatment options for adjuvant therapy and in-transit disease, resulting in extensive revisions to the supporting discussion sections. C1 [Coit, Daniel G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Thompson, John A.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Algazi, Alain] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Andtbacka, Robert] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bichakjian, Christopher K.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Carson, William E., III] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Carson, William E., III] Solove Res Inst, Columbus, OH USA. [Daniels, Gregory A.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [DiMaio, Dominick] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Ernstoff, Marc] Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH USA. [Ernstoff, Marc] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA. [Fields, Ryan C.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Fields, Ryan C.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Fleming, Martin D.] Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Gonzalez, Rene] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Guild, Valerie] Aim Melanoma, Houston, TX USA. [Halpern, Allan C.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Hodi, F. Stephen, Jr.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Joseph, Richard W.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Lange, Julie R.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Martini, Mary C.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Materin, Miguel A.] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Olszanski, Anthony J.] Fox Chase Canc Ctr, Seattle, WA USA. [Ross, Merrick I.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Salama, April K.] Duke Canc Inst, Durham, NC USA. [Skitzki, Joseph] Roswell Pk Canc Inst, Buffalo, NY USA. [Sosman, Jeff] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Swetter, Susan M.] Stanford Canc Inst, Stanford, CA USA. [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Torres-Roca, Javier F.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Trisal, Vijay] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Urist, Marshall M.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. RP Coit, DG (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 162 TC 8 Z9 8 U1 2 U2 11 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2016 VL 14 IS 4 BP 450 EP + PG 17 WC Oncology SC Oncology GA DJ3CL UT WOS:000374082300009 PM 27059193 ER PT J AU Bunn, PA Minna, JD Augustyn, A Gazdar, AF Ouadah, Y Krasnow, MA Berns, A Brambilla, E Rekhtman, N Massion, PP Niederst, M Peifer, M Yokota, J Govindan, R Poirier, JT Byers, LA Wynes, MW McFadden, DG MacPherson, D Hann, CL Farago, AF Dive, C Teicher, BA Peacock, CD Johnson, JE Cobb, MH Wendel, HG Spigel, D Sage, J Yang, P Pietanza, MC Krug, LM Heymach, J Ujhazy, P Zhou, CC Goto, K Dowlati, A Christensen, CL Park, K Einhorn, LH Edelman, MJ Giaccone, G Gerber, DE Salgia, R Owonikoko, T Malik, S Karachaliou, N Gandara, DR Slotman, BJ Blackhall, F Goss, G Thomas, R Rudin, CM Hirsch, FR AF Bunn, Paul A., Jr. Minna, John D. Augustyn, Alexander Gazdar, Adi F. Ouadah, Youcef Krasnow, Mark A. Berns, Anton Brambilla, Elisabeth Rekhtman, Natasha Massion, Pierre P. Niederst, Matthew Peifer, Martin Yokota, Jun Govindan, Ramaswamy Poirier, John T. Byers, Lauren A. Wynes, Murry W. McFadden, David G. MacPherson, David Hann, Christine L. Farago, Anna F. Dive, Caroline Teicher, Beverly A. Peacock, Craig D. Johnson, Jane E. Cobb, Melanie H. Wendel, Hans -Guido Spigel, David Sage, Julien Yang, Ping Pietanza, M. Catherine Krug, Lee M. Heymach, John Ujhazy, Peter Zhou, Caicun Goto, Koichi Dowlati, Afshin Christensen, Camilla Laulund Park, Keunchil Einhorn, Lawrence H. Edelman, Martin J. Giaccone, Giuseppe Gerber, David E. Salgia, Ravi Owonikoko, Taofeek Malik, Shakun Karachaliou, Niki Gandara, David R. Slotman, Ben J. Blackhall, Fiona Goss, Glenwood Thomas, Roman Rudin, Charles M. Hirsch, Fred R. TI Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes? SO JOURNAL OF THORACIC ONCOLOGY LA English DT Review DE Small cell lung cancer; Gene mutations; Therapy; Immunotherapy; Neuroendocrine ID PHASE-II-TRIAL; COMPREHENSIVE GENOMIC ANALYSIS; CIRCULATING TUMOR-CELLS; SOLID TUMORS; DOUBLE-BLIND; STEM-CELLS; NEUROENDOCRINE CARCINOMAS; THERAPEUTIC TARGET; AURORA KINASE; MOUSE MODEL C1 [Bunn, Paul A., Jr.; Hirsch, Fred R.] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. [Minna, John D.; Augustyn, Alexander; Gazdar, Adi F.; McFadden, David G.; Johnson, Jane E.; Cobb, Melanie H.; Gerber, David E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Ouadah, Youcef; Krasnow, Mark A.; Sage, Julien] Stanford Univ, Stanford, CA 94305 USA. [Berns, Anton] Netherlands Canc Inst, Amsterdam, Netherlands. [Brambilla, Elisabeth] Grenoble Univ, Ctr Hosp, Grenoble, France. [Rekhtman, Natasha; Poirier, John T.; Wendel, Hans -Guido; Pietanza, M. Catherine; Krug, Lee M.; Rudin, Charles M.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Massion, Pierre P.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Niederst, Matthew; Farago, Anna F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Peifer, Martin; Thomas, Roman] Univ Cologne, D-50931 Cologne, Germany. [Yokota, Jun] Inst Predict & Personalized Med Canc, Barcelona, Spain. [Yokota, Jun] Natl Canc Ctr, Res Inst, Tokyo 104, Japan. [Govindan, Ramaswamy] Washington Univ, St Louis, MO USA. [Byers, Lauren A.; Heymach, John] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wynes, Murry W.] Int Assoc Study Lung Canc, Aurora, CO USA. [MacPherson, David] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Hann, Christine L.] Johns Hopkins Sch Med, Baltimore, MD USA. [Dive, Caroline] Canc Res UK Manchester Inst, Manchester, Lancs, England. [Teicher, Beverly A.; Malik, Shakun] NCI, Bethesda, MD 20892 USA. [Peacock, Craig D.] Cleveland Clin, Cleveland, OH 44106 USA. [Spigel, David] Sara Cannon Res Inst, Nashville, TN USA. [Yang, Ping; Ujhazy, Peter] Mayo Clin, Ctr Canc, Rochester, MN USA. [Zhou, Caicun] Tongji Univ, Inst Canc, Sch Med, Shanghai 200092, Peoples R China. [Goto, Koichi] Natl Canc Ctr Hosp East, Chiba, Japan. [Dowlati, Afshin] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Dowlati, Afshin] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Christensen, Camilla Laulund] Dana Farber Canc Inst, Boston, MA 02115 USA. [Park, Keunchil] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Einhorn, Lawrence H.] Indiana Univ, Indianapolis, IN 46204 USA. [Edelman, Martin J.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Giaccone, Giuseppe] Georgetown Univ, Washington, DC USA. [Salgia, Ravi] Univ Chicago, Chicago, IL 60637 USA. [Owonikoko, Taofeek] Emory Univ, Atlanta, GA 30322 USA. [Karachaliou, Niki] Quiron Dexeus Univ Hosp, Barcelona, Spain. [Gandara, David R.] Univ Calif Davis, Ctr Comprehens Canc, Davis, CA 95616 USA. [Slotman, Ben J.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Blackhall, Fiona] Univ Manchester, Manchester, Lancs, England. [Goss, Glenwood] Univ Ottawa, Ottawa, ON, Canada. RP Hirsch, FR (reprint author), Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. EM Fred.Hirsch@ucdenver.edu RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Dive, Caroline/0000-0002-1726-8850; Cobb, Melanie/0000-0003-0833-5473 FU NCI NIH HHS [F30 CA168264, K12 CA087723, P30 CA008748, P50 CA058187, P50 CA070907] NR 165 TC 14 Z9 14 U1 6 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD APR PY 2016 VL 11 IS 4 BP 453 EP 474 DI 10.1016/j.jtho.2016.01.012 PG 22 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DJ0AT UT WOS:000373864500002 PM 26829312 ER PT J AU Hwang, DH Sholl, LM Rojas-Rudilla, V Hall, DL Shivdasani, P Garcia, ER MacConaill, LE Vivero, M Hornick, JL Kuo, FC Lindeman, NI Dong, F AF Hwang, David H. Sholl, Lynette M. Rojas-Rudilla, Vanesa Hall, Dimity L. Shivdasani, Priyanka Garcia, Elizabeth R. MacConaill, Laura E. Vivero, Marina Hornick, Jason L. Kuo, Frank C. Lindeman, Neal I. Dong, Fei TI KRAS and NKX2-1 Mutations in Invasive Mucinous Adenocarcinoma of the Lung SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; Invasive mucinous adenocarcinoma; KRAS; NKX2-1 ID THYROID TRANSCRIPTION FACTOR; FACTOR-I; BRONCHIOLOALVEOLAR CARCINOMAS; PULMONARY ADENOCARCINOMA; PROGNOSTIC-FACTOR; EXPRESSION; CANCER; EGFR; FACTOR-1; CYTOKERATIN-20 AB Introduction: Mucinous differentiation is observed in a subset of lung adenocarcinomas with unique clinical and pathological features, but the biology of these neoplasms is poorly understood. Methods: We apply targeted next-generation sequencing to characterize the mutational profiles of 21 invasive mucinous adenocarcinomas, mixed mucinous/nonmucinous adenocarcinomas, and adenocarcinomas with mucinous features of the lung and validate key findings on 954 additional lung adenocarcinomas from our institution and 514 lung adenocarcinomas from The Cancer Genome Atlas. Results: Sequencing identifies pathogenic mutations in the oncogenes Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), erb-b2 receptor tyrosine kinase 2 (ERBB2), and anaplastic lymphoma receptor tyrosine kinase (ALK) and recurrent mutations in tumor protein p53 (TP53), serine/threonine kinase 11 (STK11), NK2 homeobox 1 (NKX2-1), and SET domain containing 2 (SETD2). In the combined discovery and validation cohorts, we identify nine neoplasms with distinct molecular and pathological features. All are invasive mucinous adenocarcinomas or mixed mucinous/nonmucinous adenocarcinomas with mutations of KRAS and frameshift or nonsense mutations of NKX2-1. Immunohistochemical analysis shows that these neoplasms are associated with altered differentiation states, including loss of expression of the pulmonary marker thyroid transcription factor 1 (also called Nkx2.1) and expression of gastrointestinal markers. Conclusions: These findings describe recurrent NKX2-1 mutations in invasive mucinous adenocarcinomas of the lung and support NKX2-1 as a lineage-specific tumor suppressor gene in lung carcinogenesis. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. C1 [Hwang, David H.; Sholl, Lynette M.; Rojas-Rudilla, Vanesa; Hall, Dimity L.; Shivdasani, Priyanka; Garcia, Elizabeth R.; MacConaill, Laura E.; Vivero, Marina; Hornick, Jason L.; Kuo, Frank C.; Lindeman, Neal I.; Dong, Fei] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [MacConaill, Laura E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, 44 Binney St, Boston, MA 02115 USA. RP Dong, F (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3, Boston, MA 02115 USA. EM fdong1@partners.org NR 37 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD APR PY 2016 VL 11 IS 4 BP 496 EP 503 DI 10.1016/j.jtho.2016.01.010 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DJ0AT UT WOS:000373864500005 PM 26829311 ER PT J AU Chaft, JE Dunphy, M Naidoo, J Travis, WD Hellmann, M Woo, K Downey, R Rusch, V Ginsberg, MS Azzoli, CG Kris, MG AF Chaft, Jamie E. Dunphy, Mark Naidoo, Jarushka Travis, William D. Hellmann, Matthew Woo, Kaitlin Downey, Robert Rusch, Valerie Ginsberg, Michelle S. Azzoli, Christopher G. Kris, Mark G. TI Adaptive Neoadjuvant Chemotherapy Guided by F-18-FDG PET in Resectable Non-Small Cell Lung Cancers: The NEOSCAN Trial SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Neoadjuvant therapy; Non-small cell lung cancer; Adaptive clinical trial; F-18-FDG PET ID PATHOLOGICAL COMPLETE RESPONSE; POSITRON-EMISSION-TOMOGRAPHY; PHASE-II TRIAL; INDUCTION CHEMOTHERAPY; HISTOPATHOLOGIC RESPONSE; ADJUVANT CHEMOTHERAPY; SURVIVAL; VINORELBINE; PREDICTION; DOCETAXEL AB Introduction: Although perioperative chemotherapy improves survival in patients with resectable lung cancers, systemic recurrence remains common. Neoadjuvant chemotherapy permits response assessment and an opportunity to switch treatment regimens. Response measured by fludeoxyglucose (F-18-FDG) positron emission tomography (PET) correlates with clinical outcomes better than computed tomography (CT) does. This trial assessed PET measured response rate to alternative chemotherapy in patients with a suboptimal PET response after two cycles of neoadjuvant chemotherapy. Methods: This phase II study enrolled patients with resectable stage IB-IIIA lung cancers (primary tumor >= 2 cm and peak standard uptake value [SUVpeak] >= 4.5). Patients had a pretreatment F-18-FDG PET/CT scan before two cycles of cisplatin (or carboplatin) plus gemcitabine (squamous cell carcinoma) or pemetrexed (adenocarcinoma) and then a repeat PET/CT scan. If SUVpeak in the primary tumor decreased by at least 35%, patients continued the initial chemotherapy. Individuals with less than a 35% PET response were switched to vinorelbine plus docetaxel. Postoperative radiotherapy was recommended to all patients with positive N2 nodes. A Simon's optimal two-stage design was used to evaluate the primary end point of a PET Response in Solid Tumors-defined response rate to vinorelbine plus docetaxel in previously nonresponding patients. Results: Forty patients were enrolled. Fifteen patients (38% [95% confidence interval: 38-53]) had less than a 35% decrease in SUVpeak, and 13 received vinorelbine plus docetaxel. The study met its primary end point with 10 of 15 PET metabolic responses to alternate therapy (67%). Chemotherapy toxicities never precluded surgical exploration. Conclusions: Utilizing F-18-FDG PET/CT to assess response and change preoperative chemotherapy in nonresponding patients can improve radiographic measures of response. This adaptive approach can also be used to test new drugs, attempting to optimize perioperative chemotherapy to achieve better long-term outcomes. (C) 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. C1 [Chaft, Jamie E.; Naidoo, Jarushka; Hellmann, Matthew; Kris, Mark G.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. [Chaft, Jamie E.; Naidoo, Jarushka; Hellmann, Matthew; Kris, Mark G.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Dunphy, Mark; Ginsberg, Michelle S.] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA. [Travis, William D.] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. [Woo, Kaitlin] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Downey, Robert; Rusch, Valerie] Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA. [Azzoli, Christopher G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Chaft, JE (reprint author), Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, 300 E 66th St, New York, NY 10065 USA. EM chaftj@mskcc.org FU NCI NIH HHS [P30 CA008748, R01 CA172546] NR 30 TC 7 Z9 7 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD APR PY 2016 VL 11 IS 4 BP 537 EP 544 DI 10.1016/j.jtho.2015.12.104 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DJ0AT UT WOS:000373864500009 PM 26724474 ER PT J AU Lin, JJ Cardarella, S Lydon, CA Dahlberg, SE Jackman, DM Janne, PA Johnson, BE AF Lin, Jessica J. Cardarella, Stephanie Lydon, Christine A. Dahlberg, Suzanne E. Jackman, David M. Jaenne, Pasi A. Johnson, Bruce E. TI Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non-small cell lung cancer; EGFR; TKI; long-term survival ID GROWTH-FACTOR-RECEPTOR; CISPLATIN PLUS GEMCITABINE; RANDOMIZED PHASE-3 TRIAL; LONG-TERM SURVIVORS; OPEN-LABEL; 1ST-LINE TREATMENT; TYROSINE KINASE; CANCER PATIENTS; CARBOPLATIN-PACLITAXEL; GEFITINIB TREATMENT AB Introduction: Activating mutations in the epidermal growth factor receptor gene (EGFR) predict for prolonged progression-free survival in patients with advanced non small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy. Longterm survival outcomes, however, remain undefined. The objective of this study was to determine the 5-year survival in these patients and identify clinical factors associated with overall survival (OS). Methods: Patients with EGFR-mutant metastatic lung adenocarcinoma who had been treated with erlotinib or gefitinib at Dana-Farber Cancer Institute between 2002 and 2009 were included. OS was analyzed. Results: Among 137 patients, median progression-free survival and OS were 12.1 months (95% CI: 10.2-13.5) and 30.9 months (95% CI: 28.2-35.7), respectively. Twenty patients (14.6%) were 5-year survivors. In multivariate analysis, exon 19 deletions (hazard ratio [HR] = 0.63, 95% CI: 0.44-0.91, p = 0.01), absence of extrathoracic (HR = 0.62, 95% CI: 0.41-0.93, p = 0.02) or brain metastasis (HR = 0.48, 95% CI: 0.30-0.77, p = 0.002), and not a current smoker (HR = 0.23, 95% CI: 0.09-0.59, p = 0.002) were associated with prolonged OS. Age; sex; stage at diagnosis; liver, bone, or adrenal metastasis; specific TKI; and line of TKI therapy were not associated with OS. Conclusions: Our data suggest that the rate of 5-year survival among patients with EGFR-mutant metastatic lung adenocarcinoma treated with erlotinib or gefitinib is 14.6%. Exon 19 deletions and absence of extrathoracic or brain metastasis are associated with prolonged survival. On the basis of our findings, clinicians can gain an enhanced estimation of long-term outcomes in this population. (C) 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. C1 [Lin, Jessica J.; Cardarella, Stephanie; Lydon, Christine A.; Jackman, David M.; Jaenne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Lin, Jessica J.; Jackman, David M.; Jaenne, Pasi A.; Johnson, Bruce E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Cardarella, Stephanie] Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Jackman, David M.; Jaenne, Pasi A.; Johnson, Bruce E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St,Dana Bldg 1006J, Boston, MA 02115 USA. EM bejohnson@partners.org FU NCI NIH HHS [5R01-CA114465, P50 CA090578, P50CA090578, R01 CA114465] NR 50 TC 13 Z9 14 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD APR PY 2016 VL 11 IS 4 BP 556 EP 565 DI 10.1016/j.jtho.2015.12.103 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DJ0AT UT WOS:000373864500011 PM 26724471 ER PT J AU Asvadi, NH Anvari, A Uppot, RN Thabet, A Zhu, AX Arellano, RS AF Asvadi, Nazanin H. Anvari, Arash Uppot, Raul N. Thabet, Ashraf Zhu, Andrew X. Arellano, Ronald S. TI CT-Guided Percutaneous Microwave Ablation of Tumors in the Hepatic Dome: Assessment of Efficacy and Safety SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID HEPATOCELLULAR-CARCINOMA; RADIOFREQUENCY ABLATION; COAGULATION THERAPY; LIVER-TUMOR; DIAPHRAGM; CLASSIFICATION; EXPERIENCE; LASER AB Purpose: To evaluate the technique, efficacy, safety, and clinical outcomes of CT-guided microwave ablation of tumors in the hepatic dome. Materials and Methods: Retrospective review was conducted of 46 consecutive patients (31 men and 15 women; mean age, 64 y) treated with CT-guided microwave ablation for hepatic-dome tumors between June 2011 and December 2014. Baseline demographics of sex, tumor diagnosis, tumor location, tumor size, and technical details were recorded. Technical success was evaluated. Treatment response was assessed per European Association for the Study of the Liver criteria. Overall success and overall survival were calculated, and complications were recorded. Results: Forty-eight tumors were treated. Tumor locations included segments VIII (n = 32), VII (n = 10), and VIa (n = 6). Mean tumor size was 2.4 cm (range, 0.9-5.2 cm). Thirty-four tumors (70%) were treated following creation of artificial ascites with 0.9% normal saline solution (mean volume, 1,237 mL; range, 300-3,000 mL). The technical success rate was 100%, and the complete response rate was 94%. Overall survival rate was 73.9% over 24.7 months of follow-up. There were no major complications. Two patients experienced small, asymptomatic pneumothoraces that were aspirated at the time of the procedure and required no further treatment. Conclusions: CT-guided microwave ablation of tumors in the hepatic dome is associated With a high technical success rate, high complete response rate, and low complication rate. C1 [Asvadi, Nazanin H.; Anvari, Arash; Uppot, Raul N.; Thabet, Ashraf; Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Radiol, White 270, Boston, MA 02114 USA. [Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, White 270, Boston, MA 02114 USA. RP Asvadi, NH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Intervent Radiol, White 270, Boston, MA 02114 USA. EM nasvadi@mgh.harvard.edu RI Anvari, Arash/B-4329-2014 OI Anvari, Arash/0000-0001-5887-581X NR 28 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2016 VL 27 IS 4 BP 496 EP 502 DI 10.1016/j.jvir.2016.01.010 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA DI8MA UT WOS:000373753900005 PM 26922977 ER PT J AU Kilcoyne, A Frenk, NE Arellano, RS AF Kilcoyne, Aoife Frenk, Nathan E. Arellano, Ronald S. TI Percutaneous Cryoablation of a Metastatic Right External Iliac Lymph Node with Associated Injury to the Femoral Nerve SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter C1 [Kilcoyne, Aoife; Frenk, Nathan E.; Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. RP Kilcoyne, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2016 VL 27 IS 4 BP 611 EP 612 DI 10.1016/j.jvir.2015.12.750 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA DI8MA UT WOS:000373753900026 PM 27013010 ER PT J AU Tan, SH Yam, AWY Lawton, LN Wong, RWJ Young, RA Look, AT Sanda, T AF Tan, S. H. Yam, A. W. Y. Lawton, L. N. Wong, R. W. J. Young, R. A. Look, A. T. Sanda, T. TI TRIB2 reinforces the oncogenic transcriptional program controlled by the TAL1 complex in T-cell acute lymphoblastic leukemia SO LEUKEMIA LA English DT Letter ID ACUTE MYELOGENOUS LEUKEMIA; C/EBP-ALPHA; LINEAGE C1 [Tan, S. H.; Yam, A. W. Y.; Wong, R. W. J.; Sanda, T.] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. [Lawton, L. N.; Young, R. A.] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. [Young, R. A.] MIT, Dept Biol, Cambridge, MA USA. [Look, A. T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. [Look, A. T.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Sanda, T.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore. RP Sanda, T (reprint author), Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore.; Sanda, T (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore. EM takaomi_sanda@nus.edu.sg FU NCI NIH HHS [P01 CA109901, K99 CA157951, 1K99CA157951, 5P01CA109901] NR 15 TC 0 Z9 0 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD APR PY 2016 VL 30 IS 4 BP 959 EP 962 DI 10.1038/leu.2015.195 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA DJ3RK UT WOS:000374123100025 PM 26202930 ER PT J AU Byne, W AF Byne, William TI Regulations Restrict Practice of Conversion Therapy SO LGBT HEALTH LA English DT Editorial Material DE continuing medical education; gender identity; legislation; LGBT conversion therapy; reparative therapy; sexual orientation ID GENDER DYSPHORIA; DISORDERS; GAY C1 [Byne, William] James J Peters VA Med Ctr, Bronx, NY USA. [Byne, William] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. RP Byne, W (reprint author), James J Peters VA Med Ctr, Bronx, NY USA.; Byne, W (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM william.byne@mssm.edu NR 22 TC 0 Z9 0 U1 7 U2 10 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD APR PY 2016 VL 3 IS 2 BP 97 EP 99 DI 10.1089/lgbt.2016.0015 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DJ0ZE UT WOS:000373932100001 PM 26990275 ER PT J AU Nikbakht, H Panditharatna, E Mikael, LG Li, R Gayden, T Osmond, M Ho, CY Kambhampati, M Hwang, EI Faury, D Siu, A Papillon-Cavanagh, S Bechet, D Ligon, KL Ellezam, B Ingram, WJ Stinson, C Moore, AS Warren, KE Karamchandani, J Packer, RJ Jabado, N Majewski, J Nazarian, J AF Nikbakht, Hamid Panditharatna, Eshini Mikael, Leonie G. Li, Rui Gayden, Tenzin Osmond, Matthew Ho, Cheng-Ying Kambhampati, Madhuri Hwang, Eugene I. Faury, Damien Siu, Alan Papillon-Cavanagh, Simon Bechet, Denise Ligon, Keith L. Ellezam, Benjamin Ingram, Wendy J. Stinson, Caedyn Moore, Andrew S. Warren, Katherine E. Karamchandani, Jason Packer, Roger J. Jabado, Nada Majewski, Jacek Nazarian, Javad TI Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma SO NATURE COMMUNICATIONS LA English DT Article ID ACTIVATING ACVR1 MUTATIONS; HIGH-GRADE ASTROCYTOMAS; EXOME-SEQUENCING DATA; INTRATUMOR HETEROGENEITY; PEDIATRIC GLIOBLASTOMA; HISTONE H3.3; TUMORS; SUBGROUPS; EVOLUTION; ANNOTATION AB Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M-including H3.2K27M-mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often affect the PI3K pathway. Our findings are consistent with early tumour spread outside the brainstem including the cerebrum. The spatial and temporal homogeneity of main driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships. C1 [Nikbakht, Hamid; Li, Rui; Gayden, Tenzin; Osmond, Matthew; Papillon-Cavanagh, Simon; Bechet, Denise; Jabado, Nada; Majewski, Jacek] McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada. [Nikbakht, Hamid; Li, Rui; Osmond, Matthew; Papillon-Cavanagh, Simon; Majewski, Jacek] McGill Univ, Montreal, PQ H3A 0G1, Canada. [Nikbakht, Hamid; Li, Rui; Osmond, Matthew; Papillon-Cavanagh, Simon; Majewski, Jacek] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada. [Panditharatna, Eshini; Kambhampati, Madhuri; Nazarian, Javad] Childrens Natl Hlth Syst, Med Genet Res Ctr, Washington, DC 20010 USA. [Panditharatna, Eshini] George Washington Univ, Sch Med & Hlth Sci, Inst Biomed Sci, Washington, DC 20052 USA. [Mikael, Leonie G.; Faury, Damien; Jabado, Nada] McGill Univ, Dept Pediat, Montreal, PQ H4A 3J1, Canada. [Mikael, Leonie G.; Faury, Damien; Jabado, Nada] McGill Univ, Heath Ctr, Res Inst, Montreal, PQ H4A 3J1, Canada. [Ho, Cheng-Ying] Childrens Natl Hlth Syst, Div Pathol, Washington, DC 20010 USA. [Hwang, Eugene I.] Childrens Natl Hlth Syst, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. [Siu, Alan] George Washington Univ, Sch Med & Hlth Sci, Dept Neurol Surg, Washington, DC 20052 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Ellezam, Benjamin] Univ Montreal, Dept Pathol, CHU Ste Justine, Montreal, PQ H3T 1C5, Canada. [Ingram, Wendy J.; Moore, Andrew S.] Univ Queensland, Child Hlth Res Ctr, Brisbane, Qld 4101, Australia. [Stinson, Caedyn; Moore, Andrew S.] Univ Queensland, Diamantina Inst, Brisbane, Qld 4102, Australia. [Moore, Andrew S.] Childrens Hlth Queensland Hosp & Hlth Serv, Oncol Serv, Brisbane, Qld 4101, Australia. [Warren, Katherine E.] NCI, NIH, Bethesda, MD 20892 USA. [Karamchandani, Jason] McGill Univ, Dept Pathol, Montreal Neurol Hosp, Montreal, PQ H3A 2B4, Canada. [Packer, Roger J.] Childrens Natl Hlth Syst, Ctr Neurosci & Behav Med, Brain Tumour Inst, Washington, DC 20010 USA. [Nazarian, Javad] George Washington Univ, Sch Med & Hlth Sci, Dept Integrat Syst Biol, Washington, DC 20052 USA. RP Jabado, N; Majewski, J (reprint author), McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.; Majewski, J (reprint author), McGill Univ, Montreal, PQ H3A 0G1, Canada.; Majewski, J (reprint author), Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.; Nazarian, J (reprint author), Childrens Natl Hlth Syst, Med Genet Res Ctr, Washington, DC 20010 USA.; Jabado, N (reprint author), McGill Univ, Dept Pediat, Montreal, PQ H4A 3J1, Canada.; Jabado, N (reprint author), McGill Univ, Heath Ctr, Res Inst, Montreal, PQ H4A 3J1, Canada.; Nazarian, J (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Integrat Syst Biol, Washington, DC 20052 USA. EM nada.jabado@mcgill.ca; Jacek.majewski@mcgill.ca; JNazarian@childrensnational.org RI Moore, Andrew/I-6275-2012; Ingram, Wendy/F-7317-2010 OI Moore, Andrew/0000-0001-8062-1779; Ingram, Wendy/0000-0002-7063-1081 FU Genome Canada; Genome Quebec; Institute for Cancer Research of the Canadian Institutes for Health Research (CIHR) McGill University; Montreal Children's Hospital Foundation; NIH National Center for Advancing Translational Sciences [UL1TR000075, KL2TR000076]; Smashing Walnuts Foundation (Middleburg, VA); Zickler Family Foundation (Chevy Chase, MD); Goldwin Foundation (St Lincoln, NE); Piedmont Community Foundation (Middleburg, VA); Musella Foundation (Hewlett, NY); Mathew Larson Foundation (Franklin Lake, NJ); Brain Tumour Foundation for Children Atlanta, GA); Chair de Recherche from le Fond de Recherche en Sante au Quebec; CIHR; T.D trust/Montreal Children's Hospital Foundation FX The authors would like to express their sincere gratitude toward all the patients' families, as well as the staff at the McGill University and Genome Quebec Innovation Centre for excellent technical expertise, library preparation and sequencing. This work was performed within the context of the I-CHANGE consortium (International Childhood Astrocytoma iNtegrated Genomics and Epigenomics consortium) and supported by funding from Genome Canada, Genome Quebec, The Institute for Cancer Research of the Canadian Institutes for Health Research (CIHR) McGill University and the Montreal Children's Hospital Foundation. It was also supported by UL1TR000075 and KL2TR000076 from the NIH National Center for Advancing Translational Sciences, The Smashing Walnuts Foundation (Middleburg, VA), The Zickler Family Foundation (Chevy Chase, MD), Goldwin Foundation (St Lincoln, NE), The Piedmont Community Foundation (Middleburg, VA), The Musella Foundation (Hewlett, NY), The Mathew Larson Foundation (Franklin Lake, NJ), and Brain Tumour Foundation for Children Atlanta, GA). N.J. is a member of the Penny Cole lab and the recipient of a Chair de Recherche from le Fond de Recherche en Sante au Quebec. J.M. holds a Canada Research Chair (tier 2). T.G. is supported by a studentship from the CIHR. D.B. is supported by a studentship from the T.D trust/Montreal Children's Hospital Foundation. E.P. is a predoctoral student in the Molecular Medicine Program of the Institute for Biomedical Sciences at the George Washington University. This work is from a dissertation to be presented to the above program in partial fulfillment of the requirements for the PhD degree. NR 39 TC 6 Z9 6 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2016 VL 7 AR 11185 DI 10.1038/ncomms11185 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DI9LD UT WOS:000373823300001 PM 27048880 ER PT J AU Zang, CZ Wang, T Deng, K Li, B Hu, SE Qin, Q Xiao, TF Zhang, SH Meyer, CA He, HH Brown, M Liu, JS Xie, Y Liu, XS AF Zang, Chongzhi Wang, Tao Deng, Ke Li, Bo Hu, Sheng'en Qin, Qian Xiao, Tengfei Zhang, Shihua Meyer, Clifford A. He, Housheng Hansen Brown, Myles Liu, Jun S. Xie, Yang Liu, X. Shirley TI High-dimensional genomic data bias correction and data integration using MANCIE SO NATURE COMMUNICATIONS LA English DT Article ID GENE-EXPRESSION SIGNATURE; CELL LUNG-CANCER; ADENOCARCINOMA; TRANSCRIPTION; CHROMATIN; PROGNOSIS; ENHANCERS; SURVIVAL; SCALE AB High-dimensional genomic data analysis is challenging due to noises and biases in high-throughput experiments. We present a computational method matrix analysis and normalization by concordant information enhancement (MANCIE) for bias correction and data integration of distinct genomic profiles on the same samples. MANCIE uses a Bayesian-supported principal component analysis-based approach to adjust the data so as to achieve better consistency between sample-wise distances in the different profiles. MANCIE can improve tissue-specific clustering in ENCODE data, prognostic prediction in Molecular Taxonomy of Breast Cancer International Consortium and The Cancer Genome Atlas data, copy number and expression agreement in Cancer Cell Line Encyclopedia data, and has broad applications in cross-platform, high-dimensional data integration. C1 [Zang, Chongzhi; Li, Bo; Xiao, Tengfei; Meyer, Clifford A.; He, Housheng Hansen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Zang, Chongzhi; Li, Bo; Xiao, Tengfei; Meyer, Clifford A.; He, Housheng Hansen; Liu, X. Shirley] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02215 USA. [Zang, Chongzhi; Li, Bo; Xiao, Tengfei; Meyer, Clifford A.; He, Housheng Hansen; Brown, Myles; Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Wang, Tao; Xie, Yang] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Quantitat Biomed Res Ctr, Dallas, TX 75390 USA. [Wang, Tao] Univ Texas SW Med Ctr Dallas, Ctr Genet Host Def, Dallas, TX 75390 USA. [Deng, Ke] Tsinghua Univ, Ctr Stat Sci, Beijing 100084, Peoples R China. [Li, Bo; Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Hu, Sheng'en; Qin, Qian] Tongji Univ, Sch Life Sci, Dept Bioinformat, Shanghai 200092, Peoples R China. [Xiao, Tengfei; He, Housheng Hansen; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Xiao, Tengfei; He, Housheng Hansen; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Zhang, Shihua] Chinese Acad Sci, Acad Math & Syst Sci, Natl Ctr Math & Interdisciplinary Sci, Beijing 100190, Peoples R China. [He, Housheng Hansen] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada. [Xie, Yang] Univ Texas SW Med Ctr Dallas, Dept Bioinformat, Dallas, TX 75390 USA. [Xie, Yang] Univ Texas SW Med Ctr Dallas, Simons Comprehens Canc Ctr, Dallas, TX 75390 USA. RP Liu, XS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.; Liu, XS (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02215 USA.; Liu, XS (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.; Xie, Y (reprint author), Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Quantitat Biomed Res Ctr, Dallas, TX 75390 USA.; Xie, Y (reprint author), Univ Texas SW Med Ctr Dallas, Dept Bioinformat, Dallas, TX 75390 USA.; Xie, Y (reprint author), Univ Texas SW Med Ctr Dallas, Simons Comprehens Canc Ctr, Dallas, TX 75390 USA. EM yang.xie@utsouthwestern.edu; xsliu@jimmy.harvard.edu RI Zang, Chongzhi/D-1445-2011; OI he, housheng hansen/0000-0003-2898-3363 FU US National Institutes of Health (NIH) [U41HG7000, 1R01GM099409, 5R01CA172211, 1R01CA152301]; National Natural Science Foundation of China (NSFC) [11401338, 61422309]; Leukemia and Lymphoma Society (LLS) FX This work was partially supported by the US National Institutes of Health (NIH) grants U41HG7000 (X.S.L.), 1R01GM099409 (X.S.L.), 5R01CA172211 (Y.X.), 1R01CA152301 (Y.X.), Leukemia and Lymphoma Society (LLS) fellow award (C.Z.), and the National Natural Science Foundation of China (NSFC) grant 11401338 (K.D.) and 61422309 (S.Z.). NR 35 TC 1 Z9 2 U1 7 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2016 VL 7 AR 11305 DI 10.1038/ncomms11305 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DJ2VA UT WOS:000374062000001 PM 27072482 ER PT J AU O'Rourke, D Chen, PM Gaspard, N Foreman, B McClain, L Karakis, I Mahulikar, A Westover, MB AF O'Rourke, Deirdre Chen, Patrick M. Gaspard, Nicolas Foreman, Brandon McClain, Lauren Karakis, Ioannis Mahulikar, Advait Westover, M. Brandon TI Response Rates to Anticonvulsant Trials in Patients with Triphasic-Wave EEG Patterns of Uncertain Significance SO NEUROCRITICAL CARE LA English DT Article DE Triphasic waves; Non-convulsive status epilepticus; Encephalopathy; Generalized periodic discharges ID NONCONVULSIVE STATUS EPILEPTICUS; CRITICALLY-ILL; ENCEPHALOPATHY; DISEASE AB Background Generalized triphasic waves (TPWs) occur in both metabolic encephalopathies and non-convulsive status epilepticus (NCSE). Empiric trials of benzodiazepines (BZDs) or non-sedating AED (NSAEDs) are commonly used to differentiate the two, but the utility of such trials is debated. The goal of this study was to assess response rates of such trials and investigate whether metabolic profile differences affect the likelihood of a response. Methods Three institutions within the Critical Care EEG Monitoring Research Consortium retrospectively identified patients with unexplained encephalopathy and TPWs who had undergone a trial of BZD and/or NSAEDs to differentiate between ictal and non-ictal patterns. We assessed responder rates and compared metabolic profiles of responders and non-responders. Response was defined as resolution of the EEG pattern and either unequivocal improvement in encephalopathy or appearance of previously absent normal EEG patterns, and further categorized as immediate (within < 2 h of trial initiation) or delayed (> 2 h from trial initiation). Results We identified 64 patients with TPWs who had an empiric trial of BZD and/or NSAED. Most patients (71.9 %) were admitted with metabolic derangements and/or infection. Positive clinical responses occurred in 10/53 (18.9 %) treated with BZDs. Responses to NSAEDs occurred in 19/45 (42.2 %), being immediate in 6.7 %, delayed but definite in 20.0 %, and delayed but equivocal in 15.6 %. Overall, 22/64 (34.4 %) showed a definite response to either BZDs or NSAEDs, and 7/64 (10.9 %) showed a possible response. Metabolic differences of responders versus non-responders were statistically insignificant, except that the 48-h low value of albumin in the BZD responder group was lower than in the non-responder group. Conclusions Similar metabolic profiles in patients with encephalopathy and TPWs between responders and non-responders to anticonvulsants suggest that predicting responders a priori is difficult. The high responder rate suggests that empiric trials of anticonvulsants indeed provide useful clinical information. The more than twofold higher response rate to NSAEDs suggests that this strategy may be preferable to BZDs. Further prospective investigation is warranted. C1 [O'Rourke, Deirdre; Chen, Patrick M.; McClain, Lauren; Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,WACC 735, Boston, MA 02114 USA. [O'Rourke, Deirdre; Chen, Patrick M.; McClain, Lauren; Westover, M. Brandon] Harvard Univ, Sch Med, 55 Fruit St,WACC 735, Boston, MA 02114 USA. [Gaspard, Nicolas] Clin Univ Bruxelles, Hop Erasme ULB, Brussels, Belgium. [Gaspard, Nicolas] Yale Comprehens Epilepsy Ctr, Dept Neurol, New Haven, CT USA. [Foreman, Brandon] Univ Cincinnati, Coll Med, Dept Neurol & Rehabil Med, Cincinnati, OH USA. [Karakis, Ioannis] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Mahulikar, Advait] Wayne State Univ, Dept Neurol, Detroit, MI USA. RP Westover, MB (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,WACC 735, Boston, MA 02114 USA. EM daorourke@mgh.harvard.edu; patrick.m.chen.DM@dartmouth.edu; nicolas.gaspard@erasme.ulb.ac.be; brandon.foreman@uc.edu; LMCCLAIN@mgh.harvard.edu; ioannis.karakis@emory.edu; mwestover@mgh.harvard.edu FU Belgian Fund for Scientific Research; National Institute of Health (NIH-NINDS) [1K23NS090900-01]; Phyllis & Jerome Lyle Rappaport Foundation; Andrew David Heitman Neuroendovascular Research Fund FX DOR, PMC, AM, LM, and BF report no relevant disclosures. NG received research support from the Belgian Fund for Scientific Research. MBW received research support from the National Institute of Health (NIH-NINDS, 1K23NS090900-01), the Phyllis & Jerome Lyle Rappaport Foundation, and the Andrew David Heitman Neuroendovascular Research Fund. NR 26 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD APR PY 2016 VL 24 IS 2 BP 233 EP 239 DI 10.1007/s12028-015-0151-8 PG 7 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA DJ3JN UT WOS:000374101200012 PM 26013921 ER PT J AU Mizukami, K Akatsu, H Abrahamson, EE Mi, ZP Ikonomovic, MD AF Mizukami, Katsuyoshi Akatsu, Hiroyasu Abrahamson, Eric E. Mi, Zhiping Ikonomovic, Milos D. TI Immunohistochemical analysis of hippocampal butyrylcholinesterase: Implications for regional vulnerability in Alzheimer's disease SO NEUROPATHOLOGY LA English DT Article DE alzheimer's disease; amyloid; butyrylcholinesterase; hippocampus; tau ID SENILE PLAQUES; HYDROLYZE ACETYLCHOLINE; DYSTROPHIC NEURITES; AMYLOID PLAQUES; CEREBRAL-CORTEX; CHOLINESTERASES; BRAIN; PATHOLOGY; PROTEIN; BETA AB Studies of acetylcholine degrading enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in Alzheimer's disease (AD) have suggested their potential role in the development of fibrillar amyloid- (A) plaques (amyloid plaques). A recent genome-wide association study analysis identified a novel association between genetic variations in the BCHE locus and amyloid burden. We studied BChE immunoreactivity in hippocampal tissue sections from AD and control cases, and examined its relationship with amyloid plaques, neurofibrillary tangles (NFT), dystrophic neurites (DN) and neuropil threads (NT). Compared to controls, AD cases had greater BChE immunoreactivity in hippocampal neurons and neuropils in CA2/3, but not in the CA1, CA4 and dentate gyrus. The majority of amyloid plaques (>80%, using a pan-amyloid marker X-34) contained discrete neuritic clusters which were dual-labeled with antibodies against BChE and phosphorylated tau (clone AT8). There was no association between overall regional BChE immunoreaction intensity and amyloid plaque burden. In contrast to previous reports, BChE was localized in only a fraction (similar to 10%) of classic NFT (positive for X-34). A similar proportion of BChE-immunoreactive pyramidal cells were AT8 immunoreactive. Greater NFT and DN loads were associated with greater BChE immunoreaction intensity in CA2/3, but not in CA1, CA4 and dentate gyrus. Our results demonstrate that in AD hippocampus, BChE accumulates in neurons and plaque-associated neuritic clusters, but only in a small proportion of NFT. The association between greater neurofibrillary pathology burden and markedly increased BChE immunoreactivity, observed selectively in CA2/3 region, could reflect a novel compensatory mechanism. Since CA2/3 is generally considered more resistant to AD pathology, BChE upregulation could impact the cholinergic modulation of glutamate neurotransmission to prevent/reduce neuronal excitotoxicity in AD hippocampus. C1 [Mizukami, Katsuyoshi] Univ Tsukuba, Fac Hlth & Sport Sci, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. [Mizukami, Katsuyoshi] Univ Tsukuba, Grad Sch Comprehens Human Sci, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. [Akatsu, Hiroyasu] Nagoya City Univ, Grad Sch Med, Dept Community Based Med, Nagoya, Aichi, Japan. [Akatsu, Hiroyasu] Fukushimura Hosp, Choju Med Inst, Toyohashi, Aichi, Japan. [Abrahamson, Eric E.; Mi, Zhiping; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Abrahamson, Eric E.; Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Mizukami, K (reprint author), Univ Tsukuba, Grad Sch Comprehens Human Sci, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. EM kmizukam@taiiku.tsukuba.ac.jp FU NIH [NIA AG014449, AG025204]; Japanese Ministry of Education, Culture, Sports, Science and Technology FX We are indebted to the subjects from Choju Medical Institute, Fukushimura Hospital and Ishizaki Hospital in this study. This work was supported by NIH grants NIA AG014449 and AG025204 (MDI), and by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (KM). Ms. Lan Shao, Ms. Natsuko Kato and Ms. Megumi Mitani provided expert technical assistance. NR 39 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-6544 EI 1440-1789 J9 NEUROPATHOLOGY JI Neuropathology PD APR PY 2016 VL 36 IS 2 BP 135 EP 145 DI 10.1111/neup.12241 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DJ2AT UT WOS:000374006800003 PM 26293308 ER PT J AU Massey, CJ Suh, JD Tessema, B Gray, ST Singh, A AF Massey, Conner J. Suh, Jeffrey D. Tessema, Belachew Gray, Stacey T. Singh, Ameet TI Biomaterials in Rhinology SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Review DE biomaterials; nasal packing; removable packing; absorbable packing; hemostasis; wound healing; drug-eluting stents; endoscopic sinus surgery; rhinology; chronic rhinosinusitis ID ENDOSCOPIC SINUS SURGERY; RANDOMIZED CONTROLLED-TRIAL; MICROPOROUS POLYSACCHARIDE HEMOSPHERES; CARBOXY-METHYLATED CELLULOSE; MIDDLE MEATAL SPACER; NASAL PACKING; CHRONIC RHINOSINUSITIS; DOUBLE-BLIND; CHITOSAN GEL; FIBRIN GLUE AB Introduction Many different kinds of rhinologic biomaterials, both nonabsorbable and absorbable, have been developed over the years to improve outcomes following endoscopic sinus surgery (ESS) for patients with chronic rhinosinusitis. In particular, these products have been designed to prevent postoperative bleeding, optimize the wound healing process, and reduce inflammation. This review evaluates the most recent evidence on biomaterials used in rhinology, focusing on these outcomes after ESS. Data Sources MEDLINE, Scopus, Google Scholar, and Clinicaltrials.gov. Review Methods A primary literature search based on the listed databases was performed with combinatorial search terms. Studies were considered for review if they met a set of inclusion and exclusion criteria. Conclusions Some products have performed better than others in clinical trials, although significant heterogeneity among studies does not allow for selection of a clearly superior biomaterial. While nonabsorbable biomaterials are still effective in achieving certain outcomes, newer, absorbable substances may be just as effective and avoid the morbidity associated with nasal packing removal. Steroid-eluting biomaterials have shown promising early results in reducing inflammation and promoting wound healing. Implications for Practice Certain absorbable biomaterials, such as chitosan gel and fibrin glue, have performed well with respect to postoperative hemostasis and wound healing, although they do not address mucosal inflammation. Steroid delivery systems may play an increasingly important role in reducing disease recurrence after ESS, although more studies are needed to assess long-term outcomes. C1 [Massey, Conner J.; Singh, Ameet] George Washington Univ, Div Otolaryngol, 2300 M St NW,4th Floor, Washington, DC 20037 USA. [Suh, Jeffrey D.] Univ Calif Los Angeles, Dept Head & Neck Surg, Los Angeles, CA USA. [Tessema, Belachew] Univ Connecticut, Connecticut Sinus Ctr, Div Otolaryngol Head & Neck Surg, Farmington, CT USA. [Gray, Stacey T.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol,Dept Otolaryngol, Boston, MA 02115 USA. RP Singh, A (reprint author), George Washington Univ, Div Otolaryngol, 2300 M St NW,4th Floor, Washington, DC 20037 USA. EM ameetsingh@alum.mit.edu NR 53 TC 3 Z9 3 U1 3 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2016 VL 154 IS 4 BP 606 EP 617 DI 10.1177/0194599815627782 PG 12 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DJ2FL UT WOS:000374019100005 PM 26908551 ER PT J AU Dubreuil, M Peloquin, C Zhang, YQ Choi, HK Inman, RD Neogi, T AF Dubreuil, Maureen Peloquin, Christine Zhang, Yuqing Choi, Hyon K. Inman, Robert D. Neogi, Tuhina TI Validity of ankylosing spondylitis diagnoses in The Health Improvement Network SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE ankylosing spondylitis; electronic medical record; pharmacoepidemiology; pharmacoepidemiology ID PSORIATIC-ARTHRITIS; VALIDATION; RECORDS; UK AB Background/PurposeBecause ankylosing spondylitis (AS) is uncommon, large medical record databases offer important opportunities for pharmacoepidemiologic research. However, the validity of AS diagnoses recorded by a general practitioner (GP) is unknown. We assessed the validity of algorithms for identifying AS in The Health Improvement Network (THIN). MethodsTHIN is a database of GP records for over 10 million persons in the UK. In 2014, we administered a questionnaire to GPs of 100 adults for whom an AS diagnosis had been recorded. As high positive predictive value (PPV) is critically important in AS research, we sought to determine the PPV of an AS diagnostic code relative to the GP's clinical impression as the gold standard. Other AS algorithms included: more than one AS diagnostic code, prescription of a nonsteroidal anti-inflammatory drug (NSAID), disease modifying anti-rheumatic drug (DMARD) or biologic. ResultsIn 61 of 85 returned questionnaires, the GP's clinical impression confirmed AS yielding an overall PPV of 72%. PPV was 89% for two AS codes >7days apart, and was 86% for an AS code plus a DMARD/biologic. Sensitivity was reduced with algorithms requiring two AS codes (64%) and a DMARD/biologic prescription (30%). Algorithms requiring prescription of an NSAID, or the absence of OA or RA had lower PPV (71-75%) and higher sensitivity (95-98%). ConclusionAn AS identification algorithm of two AS diagnoses separated by >7days provided the highest PPV. This algorithm should be used for pharmacoepidemiologic studies in THIN. Copyright (c) 2016 John Wiley & Sons, Ltd. C1 [Dubreuil, Maureen] Boston Univ, Sch Med, Rheumatol Sect, 650 Albany St,Suite 200, Boston, MA 02118 USA. [Dubreuil, Maureen] VA Boston Healthcare Syst, Boston, MA USA. [Peloquin, Christine; Zhang, Yuqing; Neogi, Tuhina] Boston Univ, Sch Med, Clin Epidemiol Sect, Boston, MA 02118 USA. [Choi, Hyon K.] Massachusetts Gen Hosp, Rheumatol Sect, Boston, MA 02114 USA. [Inman, Robert D.] Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. RP Dubreuil, M (reprint author), Boston Univ, Sch Med, Rheumatol Sect, 650 Albany St,Suite 200, Boston, MA 02118 USA. EM mdubreui@bu.edu FU NIAMS NIH HHS [AR47785, P60 AR047785] NR 14 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2016 VL 25 IS 4 BP 399 EP 404 DI 10.1002/pds.3952 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DJ1ZI UT WOS:000374003100007 PM 26762622 ER PT J AU Floyd, JS Blondon, M Moore, KP Boyko, EJ Smith, NL AF Floyd, James S. Blondon, Marc Moore, Kathryn P. Boyko, Edward J. Smith, Nicholas L. TI Validation of methods for assessing cardiovascular disease using electronic health data in a cohort of Veterans with diabetes SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE validation; electronic health data; diabetes mellitus; myocardial infarction; smoking; pharmacoepidemiology ID ACUTE MYOCARDIAL-INFARCTION; ADMINISTRATIVE DATA; DATA ALGORITHMS; DATABASES; EVENTS; CODES; RISK AB BackgroundElectronic health data are routinely used to conduct studies of cardiovascular disease in the setting of the Veterans Health Administration (VA). Previous studies have estimated the positive predictive value (PPV) of International Classification of Disease, Ninth Revision (ICD-9) codes for acute myocardial infarction (MI), but the sensitivity of these codes for all true events and the accuracy of coding algorithms for prevalent disease status at baseline are largely unknown. MethodsWe randomly sampled 180 Veterans from the VA Puget Sound Health Care System who initiated diabetes treatment. The full electronic medical record was reviewed to identify prevalent conditions at baseline and acute MI events during follow-up. The accuracy of various coding algorithms was assessed. ResultsAlgorithms for previous acute events at baseline had high PPV (previous MI: 97%; previous stroke: 81%) but low sensitivity (previous MI: 38%; previous stroke: 52%). Algorithms for chronic conditions at baseline had high PPV (heart failure: 72%; coronary heart disease [CHD]: 85%) and high sensitivity (heart failure: 90%, CHD: 84%). For current smoking status at baseline, ICD-9 codes with pharmacy data had a PPV of 77% and sensitivity of 73%. The coding algorithm for acute MI events during follow-up had high PPV (80%) and sensitivity (89%) ConclusionsICD-9 codes for acute MI events during follow-up had high PPV and sensitivity. The sensitivity of ICD-9 codes for previous acute events at baseline was low, but a composite variable for baseline CHD had good accuracy. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Floyd, James S.; Smith, Nicholas L.] Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. [Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Floyd, James S.; Boyko, Edward J.] Univ Washington, Med, Seattle, WA 98101 USA. [Moore, Kathryn P.; Boyko, Edward J.; Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA USA. [Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Blondon, Marc] Univ Hosp Geneva, Div Angiol & Haemostasis, Geneva, Switzerland. [Blondon, Marc] Fac Med, Geneva, Switzerland. RP Floyd, JS (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM jfloyd@uw.edu RI Floyd, James/G-7563-2015 FU NHLBI NIH HHS [K08 HL116640, K08HL116640]; NIDDK NIH HHS [P30 DK017047] NR 16 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2016 VL 25 IS 4 BP 467 EP 471 DI 10.1002/pds.3921 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DJ1ZI UT WOS:000374003100016 PM 26555025 ER PT J AU Smits, JAJ Zvolensky, MJ Davis, ML Rosenfield, D Marcus, BH Church, TS Powers, MB Frierson, GM Otto, MW Hopkins, LB Brown, RA Baird, SO AF Smits, Jasper A. J. Zvolensky, Michael J. Davis, Michelle L. Rosenfield, David Marcus, Bess H. Church, Timothy S. Powers, Mark B. Frierson, Georita M. Otto, Michael W. Hopkins, Lindsey B. Brown, Richard A. Baird, Scarlett O. TI The Efficacy of Vigorous-Intensity Exercise as an Aid to Smoking Cessation in Adults With High Anxiety Sensitivity: A Randomized Controlled Trial SO PSYCHOSOMATIC MEDICINE LA English DT Article DE smoking; smoking cessation; intervention; randomized controlled trial; exercise; aerobic exercise; anxiety; anxiety sensitivity ID PHYSICAL-ACTIVITY; AEROBIC EXERCISE; DAILY SMOKERS; WITHDRAWAL SYMPTOMS; CIGARETTE CRAVINGS; DEPRESSION; METAANALYSIS; VALIDATION; DIMENSIONS; CHALLENGE AB Objectives: High anxiety sensitivity predicts poor smoking cessation outcomes. Aerobic exercise reduces anxiety sensitivity and aspects of the risk conferred by anxiety sensitivity. In the current study, we examined whether exercise can aid smoking cessation in adults with high anxiety sensitivity. Methods: Participants were sedentary and low-activity adult daily smokers (n = 136) with elevated prescreen anxiety sensitivity. Participants received 15 weeks of standard smoking cessation treatment (ST; cognitive behavioral therapy plus nicotine replacement therapy). In addition, participants were simultaneously randomized to 15 weeks of either an exercise intervention (ST + EX; n = 72) or a wellness education control condition (ST + CTRL; n = 64). Self-reported smoking abstinence was assessed weekly during the intervention, at the end of treatment (10 weeks after the target quit date), and at 4 and 6 months after the target quit date. Abstinence was verified by expired carbon monoxide readings and saliva cotinine. Results: Results indicated that point prevalence abstinence (PPA) and prolonged abstinence (PA) rates were significantly higher for ST + EX than for ST + CTRL at each of the major end points among persons with high anxiety sensitivity (PPA: b = -0.91, standard error [SE] = 0.393, t(1171) = -2.33, p = .020; PA: b = -0.98, SE = 0.346, t(132) = -2.84, p = .005), but not among those with low anxiety sensitivity (PPA: b = -0.23, SE = 0.218, t(1171) = -1.06, p = .29; PA: b = -0.31, SE = 0.306, t(132) = -1.01, p = .32). Conclusions: The present results suggest that exercise facilitates the odds of quit success for smokers with high levels of anxiety sensitivity and therefore may be a useful therapeutic tactic for this high-risk segment of the smoking population. C1 [Smits, Jasper A. J.; Davis, Michelle L.; Powers, Mark B.; Baird, Scarlett O.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Smits, Jasper A. J.; Davis, Michelle L.; Powers, Mark B.; Baird, Scarlett O.] Univ Texas Austin, Mental Hlth Res Inst, Austin, TX 78712 USA. [Zvolensky, Michael J.] Univ Houston, Dept Psychol, Houston, TX USA. [Zvolensky, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. [Rosenfield, David] So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. [Marcus, Bess H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Church, Timothy S.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Frierson, Georita M.] Howard Univ, Dept Psychol, Washington, DC 20059 USA. [Otto, Michael W.] Boston Univ, Dept Psychol, 64 Cummington St, Boston, MA 02215 USA. [Otto, Michael W.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Hopkins, Lindsey B.] San Francisco VA Med Ctr, Stress & Hlth Res Program, San Francisco, CA USA. [Brown, Richard A.] Univ Texas Austin, Sch Nursing, Austin, TX 78712 USA. RP Smits, JAJ (reprint author), Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA.; Smits, JAJ (reprint author), Univ Texas Austin, Mental Hlth Res Inst, Austin, TX 78712 USA. EM smits@utexas.edu OI Hopkins, Lindsey/0000-0002-0577-2961 FU National Institute on Drug Abuse [R01DA027533] FX The authors have declared that no competing interests exist. This study was funded by a grant from the National Institute on Drug Abuse (R01DA027533). The National Institute on Drug Abuse plays no role in approving the publications. NR 52 TC 4 Z9 4 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2016 VL 78 IS 3 BP 354 EP 364 DI 10.1097/PSY.0000000000000264 PG 11 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DJ1FY UT WOS:000373949900012 PM 26513517 ER PT J AU He, ZX Si, Y Jiang, T Ma, RS Zhang, Y Cao, MH Li, T Yao, ZP Zhao, L Fang, SH Yu, B Dong, ZX Thatte, HS Bi, YY Kou, JJ Yang, SF Piao, DX Hao, LR Zhou, J Shi, JL AF He, Zhangxiu Si, Yu Jiang, Tao Ma, Ruishuang Zhang, Yan Cao, Muhua Li, Tao Yao, Zhipeng Zhao, Lu Fang, Shaohong Yu, Bo Dong, Zengxiang Thatte, Hemant S. Bi, Yayan Kou, Junjie Yang, Shufen Piao, Daxun Hao, Lirong Zhou, Jin Shi, Jialan TI Phosphotidylserine exposure and neutrophil extracellular traps enhance procoagulant activity in patients with inflammatory bowel disease SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE IBD hypercoagulable disorders; phosphatidylserine; Neutrophil Extracellular Traps; procoagulant activity ID PHOSPHATIDYLSERINE EXPOSURE; EXPERIMENTAL COLITIS; BLOOD-COAGULATION; INNATE IMMUNITY; MICROPARTICLES; PLATELET; ACTIVATION; MECHANISMS; THROMBOSIS; MARKERS AB Inflammatory bowel disease (IBD)-associated thromboembolic event often lacks precise aetiology. The aim of this study was to investigate the contribution of phosphatidylserine (PS) exposure and neutrophil extracellular traps (NETs) towards the hypercoagulable state in IBD. We demonstrated that the levels of PS exposed MPs and the sources of MP-origin, platelets, erythrocytes, leukocytes and cultured endothelial cells (ECs) were higher in IBD groups than in healthy controls using flow cytometry and confocal microscopy. Wright-Giemsa and immunofluorescence staining demonstrated that the elevated NETs were released by activated IBD neutrophils or by control neutrophils treated with IBD sera obtained from patients with the active disease. MPs and MP-origin cells in IBD groups, especially in active stage, markedly shortened coagulation time and had increased levels of fibrin, thrombin and FXa production as assessed by coagulation function assays. Importantly, we found that on stimulated ECs, PS rich membranes provided binding sites for FXa and FVa, promoting fibrin formation while TNF blockage or IgG depletion attenuated this effect. Treatment of control neutrophils with TNF and isolated IgG from PR3-ANCA-positive active IBD patients also resulted in the release of NETs. Blockade of PS with lactadherin prolonged coagulation time, decreased fibrin formation to control levels, and inhibited the procoagulant enzymes production in the MPs and MP-origin cells. NET cleavage by DNase I partly decreased PCA in IBD or stimulated neutrophils. Our study reveals a previously unrecognised link between hypercoagulable state and PS exposure or NETs, and may further explain the epidemiological association of thrombosis within IBD patients. C1 [He, Zhangxiu; Si, Yu; Ma, Ruishuang; Zhang, Yan; Cao, Muhua; Li, Tao; Yao, Zhipeng; Zhao, Lu; Zhou, Jin; Shi, Jialan] Harbin Med Univ, Hosp 1, Dept Hematol, Harbin 150001, Peoples R China. [He, Zhangxiu; Hao, Lirong] Harbin Med Univ, Hosp 1, Dept Nephrol, Harbin 150001, Peoples R China. [Jiang, Tao; Piao, Daxun] Harbin Med Univ, Hosp 1, Dept Gen Surg, 23 Youzheng St, Harbin 150001, Peoples R China. [Dong, Zengxiang; Bi, Yayan] Harbin Med Univ, Hosp 1, Dept Cardiol, Harbin 150001, Peoples R China. [Yu, Bo; Kou, Junjie] Harbin Med Univ, Hosp 2, Dept Cardiol, Harbin 150001, Peoples R China. [He, Zhangxiu; Si, Yu; Ma, Ruishuang; Cao, Muhua; Fang, Shaohong; Yu, Bo; Yang, Shufen] Minist Educ, Key Lab Myocardial Ischemia, Harbin, Heilongjiang Pr, Peoples R China. [Thatte, Hemant S.; Shi, Jialan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Piao, DX (reprint author), Harbin Med Univ, Hosp 1, Dept Gen Surg, 23 Youzheng St, Harbin 150001, Peoples R China.; Hao, LR; Zhou, J; Shi, JL (reprint author), Harbin Med Univ, Hosp 1, Dept Med, 23 Youzheng St, Harbin 150001, Peoples R China. EM jialan_shi@hms.harvard.edu FU National Natural Science Foundation of China [81270588, 81470301, 81570638]; Education Doctoral Foundation of Ministry [20122307110011] FX This work was in part supported by the National Natural Science Foundation of China (81270588, 81470301 and 81570638) and the Education Doctoral Foundation of Ministry (20122307110011). NR 54 TC 6 Z9 6 U1 5 U2 10 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2016 VL 115 IS 4 BP 738 EP 751 DI 10.1160/TH15-09-0710 PG 14 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DJ0AD UT WOS:000373862900004 PM 26660948 ER PT J AU Hell, L Thaler, J Martinod, K Ay, C Posch, F Wagner, DD Pabinger, I AF Hell, L. Thaler, J. Martinod, K. Ay, C. Posch, F. Wagner, D. D. Pabinger, I. TI Neutrophil extracellular traps and tissue factor-bearing microvesicles: a liaison dangereuse causing overt DIC in cancer patients? SO THROMBOSIS RESEARCH LA English DT Meeting Abstract CT 8th International Conference on Thrombosis and Hemostasis Issues in Cancer CY APR 08-10, 2016 CL Bergamo, ITALY C1 [Hell, L.; Thaler, J.; Ay, C.; Posch, F.; Pabinger, I.] Med Univ Vienna, Dept Med 1, Clin Div Haematol & Haemostaseol, Vienna, Austria. [Martinod, K.; Wagner, D. D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Martinod, K.; Wagner, D. D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Martinod, K.; Wagner, D. D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 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 APR PY 2016 VL 140 SU S1 MA OC-16 BP S174 EP S175 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DI8DR UT WOS:000373731900046 PM 27161688 ER EF